Abstracts Archive 2005

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Delayed Defibrillation Testing in Patients Implanted with Biventricular ICD (CRT-D): A Reliable and Safe Approach

Background: Defibrillation testing (DT) at the end of the implantation of cardiac resynchronization pacemaker with a defibrillator (CRT-D) exposes heart failure (HF) patients to increased procedural risks. However, until now, delayed DT has not been assessed as a possible option in HF patients implanted with CRT-D.
Objective: Aim of the present study is to assess safety and feasibility of delayed DT in HF patients treated with CRT-D.
Material and Methods: Two hundred and eleven consecutive patients (mean age: 65 years, mean NYHA class 3.0, mean EF: 29.3%) underwent CRT-D implantation from October 1999 to December 2004. In the first 17 patients, DT was performed at the end of CRT-D implantation. In the other 194 consecutive patients, DT was performed at 2 months after CRT-D implantation. Outcome of DT, as well as "acute" LV lead dislodgment rate were evaluated in the latter group of 194 patients undergoing a delayed DT. Also, ICD function was assessed through device telemetry analysis at 2 months.
Results: At delayed DT, first shock was effective in 187 of 194 patients (96%), ineffective VF interruption at maximum energy occurred only in one patient (0.5%), and acute LV lead dislodgment was 1%. No ICD therapy failure occurred in the 2-month untested period.
Conclusion: DT performed 2 months after CRT-D implantation is safe and feasible; this is possibly related to the improvement of clinical conditions and hemodynamic status as well as greater lead stability 2 months after CRT-D.

 

Atrial overdrive pacing compared to CPAP in patients with obstructive sleep apnoea syndrome

Aims Obstructive sleep apnoea (OSA) is associated with oxygen desaturation, blood pressure increase, and neurohumoral activation, resulting in possible detrimental effects on the cardiovascular system. Continuous positive airway pressure (CPAP) is the therapy of choice for OSA. In a recent study, nocturnal atrial overdrive pacing (pacing) reduced the severity of sleep apnoea in pacemaker patients. We compared the effects of CPAP with those of pacing in patients with OSA but without pacemaker indication or clinical signs of heart failure.
Methods and results Ten patients with OSA on CPAP therapy were studied for three nights by polysomnography. During the nights that followed a night without any treatment (baseline), the patients were treated with CPAP or pacing in a random order. Pacing was performed with a temporary pacing lead. The pacing frequency was 15 b.p.m. higher than the baseline heart rate. The apnoea–hypopnoea index was 41.0 h–1 (12.0–66.6) at baseline and was significantly lower during CPAP [2.2 h–1 (0.3–12.4)] compared with pacing [39.1 h–1 (8.2–78.5)]. Furthermore, duration and quality of sleep were significantly improved during CPAP when compared with pacing.
Conclusion Nocturnal atrial overdrive pacing is no alternative therapeutic strategy to CPAP for the treatment of OSA in patients without clinical signs of heart failure and without conventional indication for antibradycardia pacing.

Ten Year Follow-Up After Radiofrequency Catheter Ablation for Atrioventricular Nodal Reentrant Tachycardia in the Early Days Forever Cured, or a Source for New Arrhythmias?

Background: Radiofrequency (RF) catheter ablation is highly effective with a low complication rate. However, lesions created by RF energy are irreversible, inhomogeneous, and therefore potentially proarrhythmic.
Objectives: The aim of this study was to examine the magnitude and importance of long-term proarrhythmic effects of RF energy.
Methods and Results: Between 1991 and 1995, 120 patients underwent RF ablation for atrioventricular nodal reentrant tachycardia (AVNRT). Patient data were collected by contacting patients and/or filling out a questionnaire, and medical files were screened for recurrent, documented arrhythmias, pharmacological treatment, and repeated EP study. Referring cardiologists were asked about recurrences of tachyarrhythmias. Fourteen patients (11%) were lost to follow-up. During a mean follow-up of 10 years, six patients died. Recurrences of AVNRT were not any more observed after 3 years after ablation. A total of 29 patients (24%) suffered from new arrhythmias, 6 from type 1 atrial flutter, 6 from atrial tachycardia, 9 from atrial fibrillation, and finally 16 from symptomatic premature atrial contractions (PACs), needing medical treatment or a combination of these arrhythmias. Nine patients underwent pacemaker implantation, 4 after developing procedural atrioventricular (AV) conduction disturbances, 2 after His ablation for permanent atrial fibrillation, 1 patient for sick sinus syndrome, and another 2 patients after developing late AV block, respectively, 7 and 9 years after ablation.
Conclusion: During long-term follow-up after RF ablation for AVNRT, no AVNRT recurrences were observed, but 29 patients (24%) suffered from new arrhythmias or late AV block. This potential proarrhythmic effect of RF energy promotes the application of alternative energy sources for ablative therapies for cardiac arrhythmias.
 

Pacemaker stress echocardiography predicts cardiac events in patients with permanent pacemaker

Purpose Noninvasive pacemaker stress echocardiography is a newly introduced method for the diagnosis of coronary artery disease in patients with a permanent pacemaker. The prognostic value of pacemaker stress echocardiography has not been studied.
Subjects and methods We studied 136 patients (mean age 64±12 years) with a permanent pacemaker who underwent pacemaker stress echocardiography for evaluation of coronary artery disease. All patients underwent pacemaker stress echocardiography by external programming (pacing heart rate up to ischemia or target heart rate).
Results Thirty-one patients (23%) had normal study results. Ischemia was detected in 75 patients (55%). During a mean follow-up of 3.5±2.4 years, 35 deaths (26%) (20 the result of cardiac causes) and 2 nonfatal myocardial infarctions (1%) occurred. The annual cardiac death rate was 1.3% in patients without ischemia and 4.6% in patients with ischemia (P=.01). The annual all-cause mortality rate was 3.1% in patients without ischemia and 7% in patients with ischemia (P=.004). The presence of ischemia during pacemaker stress echocardiography was the strongest independent predictor of cardiac death (hazard ratio 4.1, confidence interval 1.2-14.5) and all-cause mortality (hazard ratio 2.7, confidence interval 1.2-6.0) in a multivariable model.
Conclusion Myocardial ischemia during pacemaker stress echocardiography is an independent predictor of cardiac death and all-cause mortality in patients with a permanent pacemaker.
 

Determination of the Optimal Atrioventricular Interval in Sick Sinus Syndrome During DDD Pacing

Background: Although the AAI pacing mode has been shown to be electromechanically superior to the DDD pacing mode in sick sinus syndrome (SSS), there is evidence suggesting that during AAI pacing the presence of natural ventricular activation pattern is not enough for hemodynamic benefit to occur. Myocardial performance index (MPI) is a simply measurable Doppler-derived index of combined systolic and diastolic myocardial performance. The aim of this study was to investigate whether AAI pacing mode is electromechanically superior to the DDD mode in patients with SSS by using Doppler-derived MPI.
Methods: Thirty-nine SSS patients with dual-chamber pacing devices were evaluated by using Doppler echocardiography in AAI mode and DDD mode. The optimal atrioventricular (AV) interval in DDD mode was determined and atrial stimulus-R interval was measured in AAI mode. The ratio of the atrial stimulus-R interval to the optimal AV interval was defined as relative AV interval (rAVI) and the ratio of MPI in AAI mode to that in DDD mode was defined as relative MPI (rMPI).
Results: The rMPI was significantly correlated with atrial stimulus-R interval and rAVI (r = 0.57, P = 0.0002, and r = 0.67, P < 0.0001, respectively). A cutoff point of 1.73 for rAVI provided optimum sensitivity and specificity for rMPI >1 based on the receiver operator curves.
Conclusions: Even though the intrinsic AV conduction is moderately prolonged, some SSS patients with dual-chamber pacing devices benefit from the ventricular pacing with optimal AV interval. MPI is useful to determine the optimal pacing mode in acute experiment.
 

Rapid Decline in Acute Stimulation Thresholds with Steroid-Eluting Active-Fixation Pacing Leads

Background and Aim: There is an increasing use of active-fixation leads for cardiac pacing, yet concerns remain regarding initial high stimulation thresholds. The aim was to perform a detailed analysis of pacing parameters at the time of implantation to determine when lead repositioning should be considered.
Methods: We performed a prospective observational study of consecutive new pacemaker implants. Detailed analysis of pacing parameters was collected at 2-minute intervals for 10 minutes, and at day 1 and week 8 following implant.
Results: Ninety-four patients underwent implantation of 79 dual-chamber and 15 single-chamber pacemakers using active-fixation leads in both chambers. An initial threshold of >1 V was demonstrated in 45/94 (48%) ventricular leads (mean threshold 1.5 ± 0.3 V). This declined rapidly to 0.9 ± 0.3 V at 4 minutes (P < 0.01), 0.7 ± 0.3 V at 10 minutes (P < 0.01), and 0.6 ± 0.3 V at day 1 (P < 0.01). At day 1, 43/45 leads were <1 V. There were 79 atrial leads. An initial threshold of >1 V (mean 1.7 ± 0.6 V) was demonstrated in 41/79 (52%) leads falling significantly to 1.1 ± 0.5 V at 4 minutes (P < 0.01), 0.9 ± 0.4 V at 10 minutes (P < 0.01), and 0.6 ± 0.2 V at day 1 (P < 0.01). At 10 minutes, 32 of 41 leads demonstrated a threshold of <1 V with all leads <1 V at day 1. Thresholds were maintained medium term.
Conclusions: Active-fixation leads are commonly associated with initially high thresholds that fall rapidly. An initial threshold of 2 V should be provisionally accepted and retested at 4 minutes. The majority will have a threshold of <1 V the following day. A failure of a high threshold to decline at 4 minutes requires lead repositioning.
 

Potential proarrhythmic effect of biventricular pacing: Fact or myth?

Background Hemodynamic improvement from biventricular pacing is well documented; however, its electrophysiologic effects have not been systematically studied. Sporadic case reports suggest a proarrhythmic effect of biventricular pacing resulting primarily in polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF).
Objectives The purpose of this study was to report a series of patients in whom implantation of a biventricular system resulted in VT/VF storm with predominance of monomorphic VT.
Methods In a retrospective analysis of all biventricular implants over a 4-year period at a single medical center, we identified 5 of 145 patients (3.4%) who developed VT/VF after they were upgraded to a biventricular system. All patients were male, age 71 ± 8 years, with ejection fraction of 0.25 ± 0.1. Four of five patients had ischemic cardiomyopathy.
Results All patients developed incessant VT/VF within 1 week of implantation. Monomorphic VT of single morphology was noted in 3 of 5 patients, monomorphic VT of multiple morphologies in 1, and polymorphic VT/VF in 1. VT was managed by temporary discontinuation of biventricular pacing in all patients, amiodarone in 3 of 5, sotalol in 1, and beta-blocker in 1. During 11 ± 7 months of follow-up, 4 of 5 patients remain alive and are arrhythmia-free.
Conclusion Biventricular pacing may result in precipitation of VT/VF storm in a minority of patients with prior history of VT/VF. This may be the first case series reporting both monomorphic and polymorphic VT after an upgrade to a system with biventricular pacing capabilities. The arrhythmias can be managed by conventional therapy and may require temporary discontinuation of left ventricular pacing. This observation is relevant to patients receiving a biventricular pacemaker without an implantable cardioverter-defibrillator backup.
 

Atrial Overdrive Pacing for the Obstructive Sleep Apnea–Hypopnea Syndrome

Background The role of atrial overdrive pacing (AOP) in sleep apnea remains uncertain. We prospectively evaluated the effect of AOP after 24 hours and after one month in patients with the obstructive sleep apnea–hypopnea syndrome and compared it with the use of nasal continuous positive airway pressure (n-CPAP).
Methods We studied 16 patients with a moderate or severe case of the obstructive sleep apnea–hypopnea syndrome (baseline mean apnea–hypopnea index, 49) and normal left ventricular systolic function in whom a dual-chamber pacemaker had been implanted. After 48 hours, the patients were randomly assigned to AOP (pacing at 15 bpm above the spontaneous mean nocturnal heart rate) or backup atrial pacing (pacing at a heart rate below 40 bpm); the latter group began n-CPAP therapy one day later. After one month, the two groups switched therapies and were followed for an additional month. Polysomnographic studies were performed at baseline, on the first night after randomization, at crossover, and at the end of the study.
Results During AOP, no significant changes were observed in any of the respiratory variables measured. The change in the apnea–hypopnea index at one month with AOP was +0.2 (95 percent confidence interval, –2.7 to +2.3; P=0.87). In contrast, all variables improved significantly after one month of n-CPAP (change in the apnea–hypopnea index, –46.3; 95 percent confidence interval, –56.2 to –36.5; P<0.001).
Conclusions Nasal continuous positive airway pressure therapy is highly effective for the treatment of the obstructive sleep apnea–hypopnea syndrome, whereas AOP has no significant effect.

Idiopathic fascicular left ventricular tachycardia: Linear ablation lesion strategy for noninducible or nonsustained tachycardia

Background Idiopathic “fascicular” left ventricular tachycardia (IFLVT) is frequently not inducible or nonsustained at the time of planned catheter ablation. The mechanism of the arrhythmia has been suggested to be reentry involving a sizable area of the LV inferior septum extending from base toward the apex.
Objective
We tested the ability of a series of radiofrequency lesions delivered in a linear fashion to the inferior-mid septum to control ventricular tachycardia not amenable to standard mapping ablation strategies.
Methods Programmed stimulation both at baseline state and with isoproterenol after heart rate was increased by at least 25% was performed in all patients. The patients included in the study were either non-inducible or only had brief nonsustained VT not amenable to “traditional” mapping. A detailed electroanatomic map of the LV was performed in sinus rhythm. The location of the linear lesion along the inferior septum was guided by the presence of Purkinje potentials, with pacemapping as an additional guide. A linear lesion was placed perpendicular to the long axis of the ventricle approximately midway from the base to the apex in the region of the mid to mid-inferior septum. Radiofrequency lesions were delivered using a 4mm tip catheter at 50 Watts and 52 degrees for 60–90 seconds.
Results Of 122 consecutive patients who underwent ablation of idiopathic VT from 1999 to 2003, 15 had IFLVT based on standard diagnostic criteria. Six of the 15 patients (40%) had nonsustained or no inducible VT in the EP lab. The number of RF lesions ranged from 7 to 15 (mean 9). The length of the effective linear lesion ranged from 1.2 to 2.2 cm (mean 1.7 cm). Developement of left posterior fascicular block was noted in two of the six patients. However, despite the absence of development of left posterior fascicular block in the other four patients, no VT or premature ventricular beats could be induced after ablation using the same provocation maneuvers as performed in the baseline state. No spontaneous arrhythmias occurred during follow-up to 16 ± 8 months (range 6 to 30 months).
Conclusion In patients with difficult to induce or nonsustained VT with the typical right bundle branch block pattern and a superiorly directed axis on 12-lead ECG, RF energy ablation delivered in a linear fashion approximately midway to two thirds toward the apex along the mid to inferior septum and perpendicular to the plane of the septum is safe and effective for VT control.

Mechanical interruption of postinfarction ventricular tachycardia as a guide for catheter ablation

Background Mechanical trauma has been described as a helpful guide for ablation of atrial tachycardias and accessory pathways. In postinfarction ventricular tachycardia (VT), the reentrant circuit is partly endocardial and therefore may be susceptible to catheter trauma.
Objectives The purpose of this study was to determine the prevalence and significance of VT termination resulting from catheter trauma.
Methods A consecutive series of 39 patients (mean age 68 ± 7 years, ejection fraction 0.25 ± 0.02) underwent left ventricular mapping for postinfarction VT. Mapping was performed during 62 hemodynamically tolerated VTs (mean cycle length 451 ± 88 ms). Only hemodynamically tolerated VTs that did not terminate spontaneously and VTs that were reproducibly inducible were included in the study. VT termination was considered mechanical only if it was not caused by a premature depolarization.
Results In 13 of 62 VTs (21%) in 8 of 39 patients (21%), either VT terminated during catheter placement at a particular site (n = 7) or a previously reproducibly inducible VT became no longer inducible with the mapping catheter located at a particular site (n = 6). The stimulus-QRS interval was significantly shorter at sites where mechanical trauma affected the reentrant circuit compared with sites having concealed entrainment (102 ± 56 ms vs 253 ± 134 ms, P = .003). At the site that was susceptible to mechanical trauma, the pace map was identical or highly similar in 13 of 13 VTs. After radiofrequency ablation at these sites, the targeted VTs were no longer inducible. No patient had recurrence of the targeted VT during a mean follow-up of 15 ± 11 months.
Conclusions Catheter contact at a critical endocardial site can interrupt postinfarction VT or prevent its induction. Radiofrequency ablation at sites of mechanical termination of VT has a high probability of success.

Incidence and predictors of cardiac perforation after permanent pacemaker placement

Background Pericardial effusion, a sign of cardiac perforation, may complicate permanent pacemaker placement. Risk factors for development of post-permanent pacemaker effusion have not been evaluated.
Objectives The purpose of this study was to determine the predictors of symptomatic pericardial effusion after permanent pacemaker placement.
Methods The Mayo Clinic pacemaker and echocardiogram databases were cross-referenced. From 1995 to 2003, 4,280 permanent pacemakers were implanted. Fifty (1.2%) patients developed significant effusion and symptoms consistent with perforation. They were randomly matched with 100 patients without effusion after permanent pacemaker placement.
Results The strongest predictors of postimplant effusion by univariate analysis were the concomitant use of a temporary transvenous pacemaker (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.6–6.2, P = .001) or steroid use within 7 days prior to implant (HR 4.1, 95% CI 1.1–10, P = .003). Weaker predictors were use of helical screw ventricular leads, body mass index (BMI) <20, older age, and longer fluoroscopy times. Variables associated with lower risk of perforation were right ventricular systolic pressure >35 mmHg (HR 0.70, 95% CI 0.44–0.97, P = .01) or BMI >30 (HR 0.62, 95% CI 0.41–0.93, P = .01). Multivariate predictors were use of temporary pacemaker (HR 2.7, 95% CI 1.4–3.9, P = .01), helical screw leads (HR 2.5; 95% CI 1.4-3.8, P = .04), and steroids (HR 3.2, 95% CI 1.1–5.4, P = .04). Right ventricular systolic pressure >35 mmHg was the only protective factor (HR 0.70, 95% CI 0.50–0.92, P = .02).
Conclusion The incidence of postimplant effusions is low. In order to minimize periprocedural permanent pacemaker effusions, temporary pacemaker placement should be avoided unless essential, and particular care should be taken when placing a permanent pacemaker in patients who are taking steroids.
 

Predictors of appropriate implantable defibrillator therapies in patients with arrhythmogenic right ventricular dysplasia

Background Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by ventricular arrhythmias and sudden cardiac death. The risk factors for sudden death and indications for implantable cardioverter-defibrillator (ICD) placement in patients with ARVD are not well defined.
Objectives The purpose of this study was to determine which clinical and electrophysiologic variables best predict appropriate ICD therapies in patients with ARVD. Particular attention focused on whether the ICD was implanted for primary or second prevention.
Methods We enrolled 67 patients (mean age 36 ± 14 years) with definite or probable ARVD who had undergone ICD placement. Appropriate ICD therapies were recorded, and Kaplan-Meier analysis was used to compare the event-free survival time between patients based upon the indication for ICD placement (primary vs secondary prevention), results of electrophysiologic testing, and whether the patient had probable or definite ARVD.
Results Over a mean follow-up of 4.4 ± 2.9 years, 40 (73%) of 55 patients who met task force criteria for ARVD and 4 (33%) of 12 patients with probable ARVD had appropriate ICD therapies for ventricular tachycardia/ventricular fibrillation (VT/VF; P = .027). Mean time to ICD therapy was 1.1 ± 1.4 years. Eleven of 28 patients who received an ICD for primary prevention (39%) and 33 of 35 patients who received an ICD for secondary prevention (85%) experienced appropriate ICD therapies (P = .001). Electrophysiologic testing did not predict appropriate ICD interventions in patients who received an ICD for primary prevention. Fourteen patients (21%) received ICD therapy for life-threatening (VT/VF >240 bpm) arrhythmias. There was no difference in the incidence of life-threatening arrhythmias in the primary and secondary prevention groups (P = .29).
Conclusion Patients who meet task force criteria for ARVD are at high risk for sudden cardiac death and should undergo ICD placement for primary and secondary prevention, regardless of electrophysiologic testing results. Further research is needed to confirm that a low-risk subset of patients who may not require ICD placement can be identified.
 

Automatic measurement of atrial pacing thresholds in dual-chamber pacemakers: Clinical experience with atrial capture management

Background The Medtronic EnPulse™ pacemaker incorporates the new atrial capture management (ACM) algorithm to automatically measure atrial capture thresholds and subsequently manage atrial pacing outputs.
Objectives The purpose of this study was to evaluate the clinical performance of ACM.
Methods Two hundred patients with an indication for a dual-chamber pacemaker underwent implantation. ACM thresholds and manually measured atrial pacing thresholds were assessed at follow-up visits. Clinical equivalence was defined as the ACM-measured threshold being within −0.25 V to +0.5 V of the manually measured threshold. The clinician analyzed all ACM measurements performed in-office for evidence of proarrhythmia.
Results All 200 implanted patients had a 1-month visit, and validated manual and in-office ACM threshold data were available for 123 patients. The ACM threshold was 0.595 ± 0.252 V, and the manual threshold was 0.584 ± 0.233 V. The mean difference was 0.010 V with a 95% confidence interval of (−0.001, 0.021). The mean difference over all visits was 0.011 V. For all patients, the individual threshold differences were within the range of clinical equivalence at all visits. No atrial arrhythmias were observed during 892 ACM tests in 193 patients.
Conclusion This study demonstrated that the ACM algorithm is safe, accurate, and reliable over time. ACM was demonstrated to be clinically equivalent to the manual atrial threshold test in all patients at 1 month and over the entire follow-up period of up to 6 months. ACM ensures atrial capture, may save time during follow-up, and can be used to manage atrial pacing outputs.
 

Inaccurate electrocardiographic interpretation of long QT: The majority of physicians cannot recognize a long QT when they see one

Background Physicians in all fields of medicine may encounter patients with long QT syndrome (LQTS). It is important to define the percentage of physicians capable of distinguishing QT intervals that are long from those that are normal because LQTS can be lethal when left untreated.
Objectives The purpose of this study was to define the percentage of physicians in the different disciplines of medicine who can recognize a long QT when they see one.
Methods We presented the ECGs of two patients with LQTS and two healthy females to 902 physicians (25 world-renowned QT experts, 106 arrhythmia specialists, 329 cardiologists, and 442 noncardiologists) from 12 countries. They were asked to measure the QT, calculate the QTc (the QT interval corrected for the heart rate), and determine whether the QT is normal or prolonged.
Results For patients with LQTS, >80% of arrhythmia experts but <50% of cardiologists and <40% of noncardiologists calculated the QTc correctly. Underestimation of the QTc of patients with LQTS and overestimation of the QTc of healthy patients were common. Interobserver agreement was excellent among QT experts, moderate among arrhythmia experts, and low among cardiologists and noncardiologists (kappa coefficient = 0.82, 0.44, and < 0.3, respectively). Correct classification of all QT intervals as either “long” or “normal” was achieved by 96% of QT experts and 62% of arrhythmia experts, but by only <25% of cardiologists and noncardiologists.
Conclusions Most physicians, including many cardiologists, cannot accurately calculate a QTc and cannot correctly identify a long QT.
 

Extent of myocardial viability predicts response to biventricular pacing in ischemic cardiomyopathy

Background The clinical response to biventricular pacing is unpredictable, especially in patients with ischemic cardiomyopathy.
Objectives The purpose of this study was to prospectively examine the relationship between the extent of myocardial viability and the response to cardiac resynchronization therapy.
Methods Twenty-one patients with ischemic left ventricular (LV) dysfunction (left ventricular ejection fraction [LVEF] 21 ± 5%), New York Heart Association (NYHA) functional class III–IV, and QRS >120 ms received biventricular devices. Myocardial viability was assessed by myocardial contrast echocardiography, and a perfusion score index (PSI) was calculated from summed segmental perfusion scores. LV performance was assessed by echocardiography on the day after implantation and at 6 months.
Results PSI was closely correlated with acute improvement in LVEF (P = .003, r = 0.65), stroke volume (P = .02, r = 0.54), and end-systolic volume (P = .05, r = −0.49). PSI also correlated with early diastolic LV relaxation (E′, P < .05, r = 0.50) and global myocardial performance or Tei index (P = .003, r = 0.63). By multiple linear regression analysis, PSI provided incremental predictive value to the degree of dyssynchrony, measured by tissue Doppler imaging, for predicting improvement in LVEF. At 6 months, PSI remained positively correlated with improvement in ventricular performance and with reduction in LV end-diastolic dimension (P = .003, r = −0.68). PSI also influenced the clinical variables of NYHA class, 6-minute walk distance, quality-of-life score, and number of hospitalizations for heart failure.
Conclusion In patients with ischemic cardiomyopathy, the extent of myocardial viability predicts acute and long-term improvement in LV performance, exercise tolerance, and reduction in LV end-diastolic dimension with biventricular pacing.
 

Cardiac resynchronization therapy in patients with right bundle branch block: Analysis of pooled data from the MIRACLE and Contak CD trials

Objectives We pooled data from two randomized controlled trials of CRT (Multicenter InSync Randomized Clinical Evaluation [MIRACLE] and Contak CD) in order to assess outcomes of patients with RBBB.
Methods A total of 61 patients with RBBB were identified, 34 of whom were randomized to the CRT group and 27 to the control group. The data from these patients were entered into a new database and analyzed.
Results Baseline demographics were not different between the two groups (mean age 65.5 ± 11.3 years vs 69.5 ± 9.6 years; male gender 91% vs 85%; patients with coronary disease 76.5% vs 88%; QRS duration 167 ms vs 164 ms; all P = NS). Outcome variables (New York Heart Association [NYHA] class, 6-minute hall walk distance, peak oxygen consumption (VO2), Minnesota Living with Heart Failure quality-of-life scores, left ventricular ejection fraction, and norepinephrine levels) were analyzed at randomization, 3 months, and 6 months.
Conclusions (1) With the exception of NYHA class, patients with RBBB as the qualifying wide QRS did not derive significant benefit from CRT in any of the other parameters studied at 3 or 6 months. (2) RBBB patients who received active CRT showed significant improvements in NYHA class by 6 months and trends toward improvement in 6-minute walk distance, quality-of-life scores, and norepinephrine levels. However, control patients also showed significant improvement in NYHA class by 6 months but showed no improvement in objective measurements (VO2, 6-minute walk distance, left ventricular ejection fraction, and norepinephrine levels), consistent with a placebo effect. Analysis of a larger cohort of patients with RBBB undergoing CRT may demonstrate significant benefit, but the current analysis does not support the use of CRT in patients with RBBB.

Prolonged Paced QRS Duration as a Predictor for Congestive Heart Failure in Patients with Right Ventricular Apical Pacing

Background: The recent studies showed that right ventricular (RV) pacing was associated with worsening of heart failure. The aim of this study is to clarify the clinical significance of paced QRS duration during RV pacing to predict congestive heart failure (CHF) patients.
Methods and Results: This study enrolled in 92 patients with atrioventricular block who underwent initial pacemaker implantation. The paced QRS duration was automatically obtained by electrocardiography immediately after pacemaker implantation and then by routine attendance at a pacemaker clinic every 3 months. The paced QRS duration was positively correlated with left ventricular end-diastolic dimension (P < 0.05) and left ventricular end-systolic dimension (P < 0.05), and tended to negatively correlate with left ventricular ejection fraction (P = 0.0507). The paced QRS duration immediately after pacemaker implantation was 170.4 ± 18.9 ms. During a mean follow-up period of 53 ± 16 months, 16 patients developed CHF. We selected as a cut-off value the nearest whole number (190 ms) that was one standard deviation greater than the mean, and divided into two groups according to baseline paced QRS duration. Patients with a paced QRS duration of <190 ms comprised group A (n = 77, nine of which developed CHF) and the remainder comprised group B (n = 15, seven of which developed CHF). Prolonged paced QRS duration (≥190 ms) was associated with a significant increase in the overall morbidity of CHF (P < 0.05). Additionally, paced QRS duration significantly prolonged during the follow-up period among group A patients with CHF (P < 0.05), but did not change among patients without CHF.
Conclusion: We concluded that paced QRS duration can be a useful indicator of impaired left ventricular function in patients with RV pacing. Even in patients whose paced QRS duration is relatively shorter, progressive prolongation of paced QRS duration can predict the development of CHF.
 

Long-Term Mortality in Patients with Pauses in Ventricular Electrical Activity

Background: The long-term significance of ventricular pauses of ≥3.0 seconds observed on Holter monitor is unclear, as previously conducted retrospective studies have been poorly controlled. We compared the prognosis of patients with pauses ≥3.0 seconds on Holter monitor with a well-matched control group without such pauses.
Methods: Scanning the Holter database at Ochsner Clinic (n = 11,730; January 1998 to June 2003) for pauses ≥3.0 seconds identified 70 patients (pause group). Of those, 29 (37.1%) received a permanent pacemaker (PPM group) and 41 (62.9%) did not (No-PPM group). For each No-PPM patient, two patients without pauses (<2.0 seconds) exactly matched for age, sex, ejection fraction (EF), rhythm, and duration of follow-up were randomly chosen from the Holter database (control group, n = 82) and survival of the two groups was compared.
Results: Mean age was 72.5 ± 15.0 years, mean EF was 52.2 ± 12.7%, and 68.3% were men. Mean follow-up was 2.2 years (0.5–4.5 years). There was no difference in survival between the No-PPM and the control groups (82.9% vs 84.1%, P = NS). Compared with the PPM group, pauses in the No-PPM group were more commonly asymptomatic, nocturnal, and due to sinus pauses or atrial fibrillation (AF) with slow ventricular response.
Conclusions: Pauses in ventricular electrical activity ≥3 seconds on Holter monitor due to sinus pauses or AF with slow ventricular response are not predictive of heightened mortality.
 

The Effect of Losartan Versus Atenolol on Cardiovascular Morbidity and Mortality in Patients With Hypertension Taking Aspirin: The Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study

BACKGROUND: Negative interactions between angiotensin-converting enzyme inhibitors and aspirin have been reported. There are no data reported from clinical trials about possible interactions between angiotensin-II receptor antagonists and aspirin.
METHODS: The LIFE study assigned 9,193 patients with hypertension and left ventricular hypertrophy (LVH) to losartan- or atenolol-based therapy for a mean of 4.7 years, with 1,970 (21.4%) taking aspirin at baseline. The primary composite end point (CEP) included cardiovascular death, stroke, and myocardial infarction (MI). The present cohort was stratified by aspirin use at baseline.
RESULTS: Blood pressures were reduced similarly in the losartan with aspirin (n = 1,004) and atenolol with aspirin (n = 966) groups. The CEP was reduced by 32% (95% confidence interval 0.55 to 0.86, p = 0.001) with losartan with aspirin compared to atenolol with aspirin, adjusted for Framingham risk score and LVH. The test for treatment versus aspirin interaction, excluding other covariates, was significant for the CEP (p = 0.016) and MI (p = 0.037).
CONCLUSIONS: There was a statistical interaction between treatment and aspirin in the LIFE study, with significantly greater reductions for the CEP and MI with losartan in patients using aspirin than in patients not using aspirin at baseline. Further studies are needed to clarify whether this represents a pharmacologic interaction or a selection by aspirin use of patients more likely to respond to losartan treatment.
 

Junctional Rhythm—A Suitable Surrogate Endpoint in Catheter Ablation of Atrioventricular Nodal Reentry Tachycardia?

Introduction: Current AHA/ACC guidelines state that junctional rhythm (JR) is an acceptable endpoint in patients undergoing radiofrequency ablation (RFA) for narrow complex tachycardia in the presence of dual AV nodal physiology, but in the absence of inducible AVNRT. Only limited data are available on the utility of JR as a marker of successful slow pathway ablation. We sought to further characterize the sensitivity, specificity, and predictive value of JR in AVNRT ablation.
Methods: A retrospective analysis was performed of 387 consecutive patients with documented narrow complex tachycardia referred for ablation, with dual AV nodal physiology and inducible AVNRT at electrophysiological study. RFA of slow pathway was performed, with the presence or absence of JR recorded for each application and inducibility tested using atrial stimulation protocol and isoproterenol.
Results: Successful ablation was achieved in 385 of 387 patients using a total of 1,861 applications of radiofrequency energy. JR occurred in 692 applications, giving a sensitivity and specificity of JR as an indicator of successful ablation of 99.5% and 79.1% and a positive predictive value of 55.5%.
Conclusions: This study confirms that successful ablation of slow pathway seldom occurs in the absence of JR. Although JR almost invariably occurs with successful ablation, its lack of specificity and low positive predictive value questions the use of it as an endpoint in AVNRT ablations, and the guidelines should reflect this.
 

Off-Pump Coronary Artery Surgery for Reducing Mortality and Morbidity Meta-Analysis of Randomized and Observational Studies

OBJECTIVES: The purpose of this study was to assess the effects of off-pump coronary bypass surgery (OPCAB) on mortality and morbidity.
BACKGROUND: Despite its potential for reducing morbidity and mortality, OPCAB’s role in clinical practice remains controversial.
METHODS: A meta-analysis of 37 randomized controlled trials (RCTs) (n=3,449) and 22 risk-adjusted (logistic regression or propensity-score) observational studies (n=293,617) was performed. Two reviewers performed literature searches (MEDLINE, EMBASE, PubMed, reference lists), quality assessment, and data extraction. Treatment effects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs).
RESULTS: In RCTs, OPCAB was associated with reduced atrial fibrillation (OR 0.59; 95% CI 0.46 to 0.77) and trends toward reduced 30-day mortality (OR 0.91 95% CI 0.45 to 1.83), stroke (OR 0.52; 95% CI 0.25 to 1.05), and myocardial infarction (OR 0.79; 95% CI 0.50 to 1.25). Observational studies showed OPCAB to be associated with reduced 30-day mortality (OR 0.72; 95% CI 0.66 to 0.78), stroke (OR 0.62; 95% CI 0.55 to 0.69), infarction (OR 0.66; 95% CI 0.50 to 0.88), and atrial fibrillation (OR 0.78; 95% CI 0.74 to 0.82). At one to two years, OPCAB was associated with trends toward reduced mortality, but also increased repeat revascularization (RCT: OR 1.75, 95% CI 0.78 to 3.94; Observational: OR 1.35, 95% CI 0.76 to 2.39).
CONCLUSIONS: Randomized controlled trials did not find, aside from atrial fibrillation, the statistically significant reductions in short-term mortality and morbidity demonstrated by observational studies. These discrepancies might be due to differing patient-selection and study methodology. Future studies must focus on improving research methodology, recruiting high-risk patients, and collecting long-term data.
 

Eplerenone Reduces Mortality 30 Days After Randomization Following Acute Myocardial Infarction in Patients With Left Ventricular Systolic Dysfunction and Heart Failure

OBJECTIVES: This study sought to assess the impact of the selective aldosterone blocker eplerenone on mortality 30 days after randomization in patients after acute myocardial infarction (AMI) with a left ventricular ejection fraction (LVEF) 40% and clinical signs of heart failure.
BACKGROUND: In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone reduced all-cause mortality by 15% (p = 0.008) over a mean follow-up of 16 months when used with standard therapy in patients after AMI with an LVEF 40% and clinical signs of heart failure.
METHODS: We analyzed the effect of eplerenone 25 mg/day initiated 3 to 14 days after AMI (mean, 7.3 days) on the co-primary end points of time to death from any cause and the composite end point of time to death from cardiovascular (CV) causes or hospitalization for CV events, and the secondary end points of CV mortality, sudden cardiac death, and fatal/nonfatal hospitalization for heart failure, after 30 days of therapy in the EPHESUS trial.
RESULTS: At 30 days after randomization, eplerenone reduced the risk of all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone and placebo-treated patients, respectively; p = 0.004) and reduced the risk of CV mortality/CV hospitalization by 13% (8.6% vs. 9.9% in eplerenone and placebo-treated patients, respectively; p = 0.074). Eplerenone also reduced the risk of CV mortality by 32% (p = 0.003) and the risk of sudden cardiac death by 37% (p = 0.051).
CONCLUSIONS: Eplerenone 25 mg/day significantly reduced all-cause mortality 30 days after randomization (when initiated at a mean of 7.3 days after AMI) in addition to conventional therapy in patients with an LVEF 40% and signs of heart failure. Based on its early survival benefit, eplerenone should be administered in the hospital after AMI.
 

Prolongation of the fast pathway effective refractory period during cryoablation in children: A marker of slow pathway modification

Objectives Using the unique features of cryotherapy, this study assesses the short-term changes in fast pathway ERP during cryomodification of the slow pathway and examines whether these changes are a useful marker for successful slow pathway modification in children.
Methods Nineteen pediatric patients (median age 15.1 years, range 9.6–19.6 years; weight 60.7 kg, range 35.6–130.2 kg) with anterograde dual AV nodal physiology underwent slow pathway modification with catheter-based cryoablation. Programmed stimulation was performed during cryoapplications after reaching −25°C to assess fast pathway and slow pathway conduction. Data were analyzed from 59 of 237 cryoapplications where the fast pathway ERP was measured more than once (n = 13 patients).
Results For 23 of 59 applications where the slow pathway was modified, the fast pathway ERP significantly increased during cryotherapy (Δ = 33.5 ms, P <.0001). The magnitude of fast pathway ERP prolongation during cryotherapy was larger when the slow pathway was modified than when there was no effect on slow pathway conduction (33.5 ± 30.5 vs 5.8 ± 18.9 ms, P =.0005). Prolongation of fast pathway ERP by ≥20 ms had 70% sensitivity and 72% specificity for predicting slow pathway modification. Following termination of cryoapplications, which resulted in slow pathway modification, the fast pathway ERP had significantly decreased from baseline (difference 44.5 ms, P <.0001). The effect on fast pathway ERP was not related to changes in cycle length during (R2 = 0.04, P = .045) or after ablation (R2 = 0.13, P = .012).
Conclusion The fast pathway ERP prolongs during cryoapplications that result in slow pathway modification and shortens after termination of cryoapplications. The magnitude of fast pathway ERP prolongation during cryoapplication may be useful as a marker for successful slow pathway modification.
 

Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation (The PAVE Study)

Background: Chronic right ventricular pacing has been reported to promote cardiac dyssynchrony. The PAVE trial prospectively compared chronic biventricular pacing to right ventricular pacing in patients undergoing ablation of the AV node for management of atrial fibrillation with rapid ventricular rates.
Methods and Results: One hundred and eighty-four patients requiring AV node ablation were randomized to receive a biventricular pacing system (n = 103) or a right ventricular pacing system (n = 81). The study endpoints were change in the 6-minute hallway walk test, quality of life, and left ventricular ejection fraction. Patient characteristics were similar (64% male; age: 69 ± 10 years, ejection fraction: 0.46 ± 0.16; 83%, NYHA Class II or III). At 6 months postablation, patients treated with cardiac resynchronization had a significant improvement in 6-minute walk distance, (31%) above baseline (82.9 ± 94.7 m), compared to patients receiving right ventricular pacing, (24%) above baseline (61.2 ± 90.0 m) (P = 0.04). There were no significant differences in the quality-of-life parameters. At 6 months postablation, the ejection fraction in the biventricular group (0.46 ± 0.13) was significantly greater in comparison to patients receiving right ventricular pacing (0.41 ± 0.13, P = 0.03). Patients with an ejection fraction ≤45% or with NYHA Class II/III symptoms receiving a biventricular pacemaker appear to have a greater improvement in 6-minute walk distance compared to patients with normal systolic function or Class I symptoms.
Conclusion: For patients undergoing AV node ablation for atrial fibrillation, biventricular pacing provides a significant improvement in the 6-minute hallway walk test and ejection fraction compared to right ventricular pacing. These beneficial effects of cardiac resynchronization appear to be greater in patients with impaired systolic function or with symptomatic heart failure.
 

Factors Influencing Appropriate Firing of the Implanted Defibrillator for Ventricular Tachycardia/Fibrillation. Findings From the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II)

OBJECTIVES: The purpose of this study was to prospectively examine the role of clinical, laboratory, echocardiographic, and electrophysiological variables as predictors of appropriate initial implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) or death in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) population.
BACKGROUND: There is limited information regarding the determinants of appropriate ICD therapy in patients with reduced ventricular function after a myocardial infarction.
METHODS: We used secondary analysis in one arm of a multicenter randomized clinical trial in patients with a previous myocardial infarction and reduced left ventricular function.
RESULTS: We analyzed baseline and follow-up data on 719 patients enrolled in the ICD arm of the MADIT-II study. Appropriate ICD therapy was observed in 169 subjects. Clinical, laboratory, echocardiographic, and electrophysiological variables, along with measures of clinical instability such as interim hospitalization for congestive heart failure (IH-CHF) and interim hospitalization for coronary events (IH-CE), were examined with proportional hazards models and Kaplan-Meier time-to-event curves before and after first interim hospitalization. Interim hospitalization-CHF, IH-CE, no beta-blockers, digitalis use, blood urea nitrogen (BUN) >25, body mass index (BMI) 30 kg/m2, and New York Heart Association functional class >II were associated with increased risk for appropriate ICD therapy for VT, VF, or death. In a multivariate (stepwise selection) analysis, IH-CHF was associated with an increased risk for the end point of either VT or VF (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.69 to 3.74, p < 0.001) and for the combined end point of VT, VF, or death (HR 2.97, 95% CI 2.15 to 4.09, p < 0.001). Interim hospitalization-CE was associated with an increased risk for VT, VF, or death (HR 1.66, 95% CI 1.09 to 2.52, p = 0.02).
CONCLUSIONS: These results provide important mechanistic information, suggesting that worsening clinical condition and cardiac instability, as reflected by an IH-CHF or IH-CE, are subsequently associated with a significant increase in the risk for appropriate ICD therapy (for VT/VF) and death.
 

Catheter Ablation of Long-Lasting Persistent Atrial Fibrillation: Critical Structures for Termination

Background: The relative contributions of different atrial regions to the maintenance of persistent atrial fibrillation (AF) are not known.
Methods: Sixty patients (53 ± 9 years) undergoing catheter ablation of persistent AF (17 ± 27 months) were studied. Ablation was performed in a randomized sequence at different left atrial (LA) regions and comprised isolation of the pulmonary veins (PV), isolation of other thoracic veins, and atrial tissue ablation targeting all regions with rapid or heterogeneous activation or guided by activation mapping. Finally, linear ablation at the roof and mitral isthmus was performed if sinus rhythm was not restored after addressing the above-mentioned areas. The impact of ablation was evaluated by the effect on the fibrillatory cycle length in the coronary sinus and appendages at each step. Activation mapping and entrainment maneuvers were used to define the mechanisms and locations of intermediate focal or macroreentrant atrial tachycardias.
Results: AF terminated in 52 patients (87%), directly to sinus rhythm in 7 or via the ablation of 1–6 intermediate atrial tachycardias (total 87) in 45 patients. This conversion was preceded by prolongation of fibrillatory cycle length by 39 ± 9 msec, with the greatest magnitude occurring during ablation at the anterior LA, coronary sinus and PV-LA junction. Thirty-eight atrial tachycardias were focal (originating dominantly from these same sites), while 49 were macroreentrant (involving the mitral or cavotricuspid isthmus or LA roof). Patients without AF termination displayed shorter fibrillatory cycles at baseline: 130 ± 14 vs 156 ± 23 msec; P = 0.002.
Conclusion: Termination of persistent AF can be achieved in 87% of patients by catheter ablation. Ablation of the structures annexed to the left atrium—the left atrial appendage, coronary sinus, and PVs—have the greatest impact on the prolongation of AF cycle length, the conversion of AF to atrial tachycardia, and the termination of focal atrial tachycardias.
 

Chronic Hemodynamic Effects After Radiofrequency Catheter Ablation of Frequent Monomorphic Ventricular Premature Beats

Introduction: Radiofrequency catheter ablation (RFCA) of severely symptomatic monomorphic ventricular premature beats (VPBs) is reported to be a safe and effective treatment option. However, the chronic hemodynamic effects of these VPBs have not been precisely evaluated.
Methods and Results: We sought to investigate chronic effects after decreasing the number of VPBs by RFCA. A total of 47 patients who had no underlying heart disease and frequent monomorphic VPBs, consisting of more than 10,000 beats per day (24,194 ± 12,516 beats per day), were enrolled. Patients were treated with RFCA and followed up over 6 months as outpatients. Echocardiography and serum B-type natriuretic peptide (BNP) level were repeatedly checked before and after RFCA. In 38 patients, whose VPBs were dramatically decreased to less than 1,000 beats per day by successful RFCA, left ventricular (LV) end-diastolic dimension (LVEDd) and end-systolic dimension (LVESd) measured by echocardiography decreased significantly (LVEDd: 50 ± 5 to 48 ± 5 mm, P < 0.01; LVESd: 33 ± 7 to 30 ± 6 mm, P < 0.01) in association with improvement of BNP level (39.9 ± 34.1 to 16.8 ± 10.3 pg/mL, P = 0.0001). In nine patients, whose VPBs were treated unsuccessfully by RFCA or that recurred, LV dimensions and BNP level did not change during the follow-up period.
Conclusion: Significant improvement in LV dimensions and serum BNP level appeared to indicate that RFCA of VPBs ameliorated occult cardiac dysfunction induced by frequent VPBs.
 

“Cardioneuroablation” – new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation

Cardiac neuroablation is a new technique for management of patients with dominantly adverse parasympathetic autonomic influence. The technique is based on radiofrequency (RF) ablation of autonomic connections in the three main ganglia around the heart. Their connections are identified by Fast-Fourier Transforms (FFTs) of endocardial signals: sites of autonomic nervous connections show fractionated signals with FFTs shifted to the right. In contrast, normal myocardium without these connections does not show these features. RF-ablation is thought to inflict permanent damage on the parasympathetic autonomic influence because its cells are adjacent to the heart whereas sympathetic cells are remote. Twenty-one patients with a mean age of 48 years, neurally mediated reflex syncope in six, functional high grade atrioventricular block in seven and sinus node dysfunction in 13 (there is overlap between the second and third groups) were treated. Follow-up for a mean of 9.2 months demonstrated success in all cases with relief of symptoms. No complications occurred.
 

Atrial pacing and sensing characteristics in heart failure patients undergoing cardiac resynchronization therapy

Patients with heart failure and sinus rhythm undergoing cardiac resynchronization therapy (CRT) require the proper detection of atrial signals and reliable atrial pacing for AV-synchronous ventricular pacing. The study aim was to compare atrial pacing and sensing characteristics in patients with transvenous CRT and patients with standard pacing indications.
Methods The study group consisted of 31 heart failure patients with depressed left ventricular function and bundle branch block, and the control group of 124 patients with dual-chamber pacemakers because of standard pacing indications. The bipolar steroid-eluting atrial screw-in lead Tendril DX 1388 T (St. Jude Medical) was implanted and connected to pulse generators that provide similar diagnostic features. The unipolar pacing threshold at 0.4ms duration, bipolar sensing threshold, and unipolar pacing impedance were determined at implantation and after 1, 3, and 6 months.
Results At implantation, the atrial pacing threshold was significantly higher in the CRT group than in the control group, 1.07±0.99V versus 0.74±0.36V (P<0.01). Similar pacing thresholds were recorded after 1 month. The pacing threshold in the CRT group was significantly higher at 1.46±0.92V after 3 and 1.50±0.94V after 6 months (control group: 0.96±0.25V at month 3; 0.98±0.32V at month 6; P<0.05). Sensing threshold was similar at implantation with 2.36±1.87mV in the CRT and 2.54±0.78mV in the control group. The sensing threshold in the CRT group decreased to 1.64±0.86mV after 3 and to 1.71±0.71mV after 6 months and was significantly lower compared with the control group (2.16±0.57mV at month 3; 2.27±0.98mV at month 6; P<0.05). At implant, the atrial pacing impedance was not different between the two groups with 443±156ohms in the CRT and 416±116ohms in the control group. During follow-up, the impedance became significantly lower in the CRT group compared with the control group (404±84ohms versus 452±101ohms at month 3; P<0.05).
Conclusions Compared with patients with standard pacing indications, CRT recipients have less good electrical characteristics in the atrium. Atrial pacing and sensing function should be closely monitored in CRT patients.
 

What is the “Optimal” follow-up schedule for ICD patients?

Background In the absence of comparative studies, recommended routine follow-up (FU) intervals for implantable cardioverter defibrillator (ICD) patients range from 1 to 6 months; most patients are followed at 3 month intervals.
Methods Six hundred and eighteen ICD patients were routinely seen 4 weeks after implant and then every 3 months. Unplanned visits (UPV) were either patient initiated or due to manufacturer recalls. FU visits included patient history/examination, ICD interrogation, pacing/sensing threshold and pacing/shock impedance. Chest X-rays were performed every 6 months. To validate FU interval recommendations, a comparative analysis on the detection of complications was performed, relying either on the information of every, or of every other FU visit, i.e., on 3 or 6 month intervals.
Results During 3.3±2.8 years, 137 complications occurred in 110 patients (17%). However, identification of only 34% was dependent on the FU schedule, since the mode of detection was ICD interrogation in 38 and history/physical examination in nine patients. The remainder was diagnosed by UPV in 47, manufacturer recall in seven, accidental discovery during device replacement in two, and routine X-ray in 34 patients. Complication free survival at 2 years was 86.4% for patients implanted before 1999, and 89.2% thereafter (P=0.003). Regarding 6 rather than 3 month FU intervals, a theoretical maximum delay of 3 months in the detection of potentially life-threatening complications would have occurred in 1.7% of all patients. For those implanted after 1999, this related to only 0.9%.
Conclusions ICD-related complications detected during routine FU visits are relatively rare, particularly with newer generation ICD systems. Thus, 6 month FU intervals appear to be safe. With new developments such as patient alert features and telemedical data transmission, FU intervals in ICD clinics might even be further extended.
 

Malignant Entity of Idiopathic Ventricular Fibrillation and Polymorphic Ventricular Tachycardia Initiated by Premature Extrasystoles Originating From the Right Ventricular Outflow Tract

OBJECTIVES: The aim of this study was to assess the clinical characteristics and the efficacy of radiofrequency catheter ablation (RFCA) for idiopathic ventricular fibrillation (VF) and/or polymorphic ventricular tachycardia initiated by ventricular extrasystoles originating from the right ventricular outflow tract (RVOT).
BACKGROUND: Ventricular fibrillation and/or polymorphic ventricular tachycardia are occasionally initiated by ventricular extrasystoles originating from the RVOT in patients without structural heart disease.
METHODS: Among 101 patients without structural heart disease in whom RFCA was conducted for idiopathic ventricular tachyarrhythmias arising from the RVOT, we examined the clinical characteristics and the efficacy of RFCA in 16 patients with spontaneous VF and/or polymorphic ventricular tachycardia initiated by the ventricular extrasystoles originating from the RVOT.
RESULTS: Among 16 patients, spontaneous episodes of VF were documented in 5 patients, and 11 patients had prior episodes of syncope. Holter recordings showed frequent isolated ventricular extrasystoles with the same morphology as that of initiating ventricular extrasystoles, and non-sustained polymorphic ventricular tachycardia with short cycle length (mean of 245 ± 28 ms) in all 16 patients. Radiofrequency catheter ablation by targeting the initiating ventricular extrasystoles eliminated episodes of syncope, VF, and cardiac arrest in all patients during follow-up periods of 54 ± 39 months.
CONCLUSIONS: Our data suggest that the malignant entity of idiopathic VF and/or polymorphic ventricular tachycardia was occasionally present in patients with idiopathic ventricular arrhythmias arising from the RVOT. Radiofrequency catheter ablation was effective as a treatment option for this entity.
 

Diagnosis of Unexplained Cardiac Arrest. Role of Adrenaline and Procainamide Infusion

Background--Cardiac arrest with preserved left ventricular function may be caused by uncommon genetic conditions. Although these may be evident on the ECG, long-term monitoring or provocative testing is often necessary to unmask latent primary electrical disease.
Methods and Results--Patients with unexplained cardiac arrest and no evident cardiac disease (normal left ventricular function, coronary arteries, and resting corrected QT) underwent pharmacological challenge with adrenaline and procainamide infusions to unmask subclinical primary electrical disease. Family members underwent noninvasive screening and directed provocative testing on the basis of findings in the proband. Eighteen patients (mean±SD age, 41±17 years; 11 female) with unexplained cardiac arrest were assessed. The final diagnosis was catecholaminergic ventricular tachycardia (CPVT) in 10 patients (56%), Brugada syndrome in 2 patients (11%), and unexplained (idiopathic ventricular fibrillation) in 6 patients (33%). Of 55 family members (mean±SD age, 27±17 years; 33 female), 9 additional affected family members were detected from 2 families, with a single Brugada syndrome patient and 8 CPVT patients.
Conclusions--Provocative testing with adrenaline and procainamide infusions is useful in unmasking the etiology of apparent unexplained cardiac arrest. This approach helps to diagnose primary electrical disease, such as CPVT and Brugada syndrome, and provides the opportunity for therapeutic intervention in identified, asymptomatic family members who harbor the same disease.

 

Evaluation of left bundle branch block as a reversible cause of non-ischaemic dilated cardiomyopathy with severe heart failure. A new concept of left ventricular dyssynchrony-induced cardiomyopathy

Objectives We sought to determine if amelioration of left bundle branch block (LBBB)-induced contraction disturbances achieved by left ventricular (LV)-based pacing could result in sustained reversal of severe LV dysfunction in certain patients with chronic heart failure due to non-ischaemic cardiomyopathy.
Background It has been shown that LBBB induces asynchronous contraction of LV. However, whether such a functional contraction disturbance, if present for an extended period of time, could account for a dilated cardiomyopathy remains unknown.
Methods The study population comprised 29 patients with dilated cardiomyopathy, sinus rhythm, LBBB and severe heart failure (14 patients in New York Heart Association (NYHA) class III and 15 in class IV). Patients were followed prospectively after resynchronization therapy. LV function was considered to be normalized when ejection fraction (EF) was >50% at 1 year.
Results Five among the 29 patients (17%: group 1) demonstrated both complete normalization of LV function following resynchronization therapy (EF: from 19±6 to 55±3%, P=0.001) and clinical improvement (mean NYHA class: 3.4±0.5 to 1.8±0.4, P=0.02; 6-min walk distance: 300±136 to 444±75m, P=0.12; peak VO2: 11.9±4 to 15.8±2ml/min/kg, p=0.03). Among the remaining 24 patients (83%: group 2) EF improved but did not normalize (from 21±8 to 23±11%, ns). Baseline clinical features could not predict which patients would exhibit the reversal of LV dysfunction.
Conclusions
Normalization of LV function 1 year after resynchronization therapy in a small but important number of patients suggests that long-standing LBBB may be a newly identified reversible cause of cardiomyopathy.
 

Headaches and the Treatment of Blood Pressure Results From a Meta-Analysis of 94 Randomized Placebo-Controlled Trials With 24 000 Participants

Background— Uncertainty exists over whether blood pressure–lowering drugs prevent headache.
Methods and Results— A meta-analysis was carried out of the 94 randomized placebo-controlled trials of 4 different classes of blood pressure–lowering drugs (thiazides, ß-blockers, ACE inhibitors, and angiotensin II receptor antagonists) in fixed doses in which data on headache were reported. There were 17 641 participants who were allocated blood pressure–lowering drugs and 6603 who were allocated placebo. Treatment lowered systolic and diastolic blood pressures by 9.4 and 5.5 mm Hg, respectively, on average. One third fewer people on average reported headache in the treated groups (8.0%) than the placebo groups (12.4%) (odds ratio, 0.67; 95% CI, 0.61 to 0.74; P<0.001). About 1 in 30 treated persons benefited by having headache prevented. The prevalence of headache was reduced (P<0.001) in trials of each of the 4 classes of drugs.
Conclusions— Our results show that blood pressure–lowering drugs prevent a significant proportion of headaches. That this effect is seen with pharmacologically unrelated classes of drugs indicates that it is likely to be due to the reduction in blood pressure per se, the only recognized action that the drugs have in common. This in turn indicates that high blood pressure is a cause of headache, but this conclusion is not supported by observational studies of blood pressure and headache. The uncertainty over whether high blood pressure causes headache does not, however, detract from the practical benefits of the use of blood pressure–lowering drugs in preventing headaches and cardiovascular disease.
 

Significance of Tilt Table Testing in Patients with Suspected Arrhythmic Syncope and Negative Electrophysiologic Study

Background: The diagnostic significance of a tilt table test (TTT) in patients with a suspected arrhythmic etiology for syncope and negative electrophysiologic study (EPS) has not been previously assessed comparing the TTT results with the findings of prolonged monitoring using an implantable loop recorder (ILR). We sought to assess the diagnostic yielding of TTT in patients with suspected arrhythmic syncope and negative EPS.
Methods and Results: In 81 patients with suspected arrhythmic etiology for syncope and negative EPS, TTT was performed and an ILR implanted regardless the results of TTT. TTT was positive in 38 patients. During follow-up, syncope or presyncope recurred in 32 patients (39.5%). No differences were found in recurrence rates in patients with positive and negative TTT (31.5% vs 46.5%, P = ns). According to rhythm registered during ILR activation, mechanisms of syncopal events were classified as: arrhythmic (atrioventricular [AV] block and ventricular tachycardia; n = 18), neurally mediated (sinus bradycardia and sinus pause; n = 9), and indeterminate (normal sinus rhythm; n = 5). There was no statistical association between the results of TTT and the mechanism of syncope.
Conclusions: In patients with a suspected arrhythmic etiology for syncope and a negative EPS, TTT is of little value to predict the mechanism of syncope and the ILR implantation seems to be a useful and safe diagnostic strategy.
 

Blood glucose: A strong risk factor for mortality in nondiabetic patients with cardiovascular disease

Background The prognostic significance of blood glucose (BG) for nondiabetic patients in a stable chronic phase of cardiovascular disease (CVD) has been sparsely investigated, especially for glucose within the normal range. In particular, it is unknown if for these patients there is a graded relation of mortality to glucose or if there is a lower threshold.
Methods We used the Framingham Heart Study 30-year data to determine 2-year all-cause, cardiovascular mortality (CVM), and non-CVM risk adjusted for age, sex, and typical cardiovascular risk factors (systolic blood pressure, total cholesterol, body mass index, cigarette smoking, and use of antihypertensive drugs) by levels of random whole BG for non–glucose-intolerant subjects (glucose intolerance includes diabetes mellitus) with existing CVD.
Results There were steep graded relations of 2-year all-cause, CVM, and non-CVM to BG throughout the normal and subdiabetic range with no evidence of a lower threshold. Two-year mortality continuously increased from 2.99% at the bottom of the normal range (BG = 60 [plasma equivalent = 67] mg/dL) to 7.23% at the top of the normal range (89 [plasma equivalent = 100] mg/dL) (a 2.42-fold increase) and then continued to further continuously increase, reaching 11.38% at 119 [plasma equivalent = 133] mg/dL, the top of the glucose range considered (P for trend <.0001). There were analogous steep increases for CVM and non-CVM.
Conclusions Blood glucose, even within the normal range, is a strong independent predictor of 2-year all-cause, CVM, and non-CVM in nondiabetic subjects with CVD and therefore of prognostic significance for these high-risk patients.
 

Efficacy and Safety of Cryoenergy in the Ablation of Atrioventricular Reentrant Tachycardia Substrates in Children and Adolescents

Introduction: Cryoenergy has evolved as a safe and effective alternative for ablation of arrhythmia substrates in adult patients. Due to two specific features, cryomapping and cryoadhesion, this technique appears very attractive for pediatric patients minimizing complications and fluoroscopy time. The aim of the study was to investigate efficacy and safety of cryoenergy in the ablation of supraventricular tachycardia (SVT) substrates in pediatric patients.
Patients and Methods: Thirty-two patients (mean age: 10.1 ± 3.5 years) with SVT (accessory pathways: n = 19; atrioventricular nodal reentrant tachycardia (AVNRT): n = 13) underwent electrophysiological study under the guidance of the LocaLisa® system. Cryomapping at 30°C was performed to predict cryoablation outcome and to ascertain AV conduction. Cryoenergy was delivered subsequently at the same spot (cryoablation at 70°C) as verified by the LocaLisa® system.
Results: Successful cryoablation was achieved in 24 of 32 patients (75%). A median of two (1 10) cryoablations were delivered. In the remaining 8 patients, radiofrequency (RF) current application was effective in 5 resulting in an overall success rate of 90.6%. In 4 patients with an accessory pathway cryomapping was not predictive for successful cryoablation (negative predictive value 66.6%). In 3 additional patients with AVNRT transient high-grade AV block occurred during cryoablation despite previous "safe" cryomapping at the same location. No other major complications were noted.
Conclusion: Cryoablation of SVT substrates in pediatric patients was associated with a lower success rate compared to RF catheter ablation. Cryomapping decreased the number of permanent lesions but did not predict cryoablation outcome in all tachycardia substrates.
 

Reproducibility of nitrate-stimulated tilt testing in patients with suspected vasovagal syncope and a healthy control group

Objective Nitrate-stimulated tilt testing may be used to diagnose vasovagal syncope or to guide therapy. To date, the reproducibility of the test in patients with clinically suspected vasovagal syncope and healthy controls is undetermined. A high reproducibility is a prerequisite for correct interpretation of the test result. This study investigates the reproducibility of a nitrate-stimulated tilt test in patients with clinically suspected vasovagal syncope and a healthy control group.
Methods and Results We studied 43 patients (24 women, 19 men) with a typical history of vasovagal syncope and 18 healthy controls (3 women, 15 men). We used a combined tilt protocol with a 30-minute passive and 15-minute nitrate-stimulated phase. The second tilt test was performed 16 ± 12 days after the first. In both patients and controls, overall positive tilt responses were reproduced in the second test in 100%. In contrast to this, the reproducibility of an overall negative test was 50% in patients but 93% in controls. Overall hemodynamic responses to tilt were reproducible in 80%.
Conclusion Nitrate-stimulated tilt testing in both patients with suspected vasovagal syncope and controls has an excellent reproducibility of positive results but a moderate reproducibility of negative results. Importantly, these results are still valid at a repeat interval of 2 weeks and longer. These data suggest that in patients with suspected vasovagal syncope, a nitrate-stimulated tilt test may provide a suitable tool to evaluate the efficacy of a therapeutic approach.
 

Atrial Response to Ventricular Antitachycardia Pacing Discriminates Mechanism of 1:1 Atrioventricular Tachycardia

Background: Inappropriate shocks from implantable cardioverter defibrillators (ICD) remain a significant clinical problem despite device discrimination algorithms. The atrial response to antitachycardia pacing (ATP) may determine the mechanism of 1:1 A:V tachycardia.
Methods: For this study we refer to sinus tachycardia, atrial tachycardia (AT), atrial fibrillation, and flutter as atrial tachycardia (AT), and all other tachycardia as "non-AT." Three atrial response patterns during the burst of ATP were determined. The atrial cycle length (ACL) may be unchanged (type 1) indicating AT. The ACL may show variation during ATP (type 2) indicating variable VA block and does not discriminate between an AT and a non-AT mechanism, in which case a default diagnosis of non-AT is made. The ACL may accelerate to the ATP cycle length (type 3) indicating entrainment. A VAAV response at the end of ATP was considered diagnostic of AT (type 3A) whereas a VAV or VVA response was considered a non-AT mechanism (type 3B). This algorithm was applied to ICD tracings from 68 episodes of spontaneous 1:1 A:V tachycardia that had 136 sequences of ATP administered. The rhythm "truth" was determined by consensus of two experienced clinicians.
Results: The algorithm correctly identified AT with a sensitivity of 71.9% (95% CI: 67.1 73.6), and specificity of 95% (83.5 99.1). The PPV was 97.2% (90.9 99.5), and NPV 58.5% (51.4 61.0). Kappa was 0.57 (0.43 0.62). If used clinically the algorithm would have aborted 53.3% (8/15) of inappropriate shocks delivered into an AT-mechanism tachycardia and would not have withheld a shock for any episode of VT.
Conclusion: Analysis of atrial response patterns during and after ventricular ATP can successfully discriminate tachycardia mechanism and may reduce inappropriate ICD shocks.
 

Randomized comparison of anterolateral versus anteroposterior electrode position for biphasic external cardioversion of atrial fibrillation

Background In biphasic external cardioversion (CV) of atrial fibrillation (AF), the influence of different electrode positions on efficacy and incidence of early recurrent atrial fibrillation is not known. This study compared anteroposterior (AP) vs anterolateral (AL) electrode positioning.
Methods Consecutive patients referred for CV of persistent AF were randomized either to an AP or an AL electrode position. Biphasic external CV was performed with standardized electrode positions and rising energy delivery.
Results Both groups (N = 123, mean age 66 years, 71% male, 83% with structural cardiovascular disease or hypertension) did not differ concerning age, sex, body mass index, chronic antiarrhythmic therapy, duration of AF, left ventricular ejection fraction, and left atrial diameter. Cumulative success rates were comparable (AP 94.9% vs AL 95.2%, P = ns). First-shock efficacy did not differ (AP 78.3% vs AL 74.6%, P = ns). Early recurrent atrial fibrillation (AF relapse <1 minute after successful CV) occurred in 8.1% (AP 11.6% vs AL 4.8%, P = ns). Mean number of shocks was 1.3 per patient with the AP configuration and 1.4 per patient with the AL configuration (P = ns). Mean cumulative energy delivery was also comparable (AP 171 WS vs AL 198 WS, P = ns).
Conclusions Both electrode positions are similar in biphasic external CV of AF with regard to acute success and early recurrent atrial fibrillation. Also, the number of shocks needed and energy delivery are comparable with both electrode configurations.
 

Efficacy and Safety of Radiofrequency Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia in the Elderly

Introduction: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common regular supraventricular tachycardia in the general population as well as in elderly patients. The purpose of the study was to investigate the success and complication rate particularly regarding the induction of an atrioventricular (AV) block by radiofrequency (RF) ablation in elderly patients with and without a preexisting AV block.
Methods and Results: Between February 1998 and July 2004, all patients with symptomatic AVNRT referred for slow-pathway ablation in our institution were included and divided into two groups: group 1 patients younger than 75 years (n = 508) and group 2 patients 75 years (n = 70).
A preexisting prolonged PR interval was present in 17 (3.3%) patients of group 1 and in 26 (37%, P < 0.0001) patients of group 2. Following successful slow-pathway ablation (follow-up time group 1: 37 ± 22, group 2: 37 ± 24 months) no induction of an AV block was observed in group 2 but in four patients of group 1 (0.79%) a complete heart block was induced requiring a pacemaker implantation. In group 1, 15 (2.95%) patients with a recurrence of AVNRT were readmitted for a repeat ablation procedure. No recurrences occurred in group 2.
Conclusion: Despite a higher incidence of preexisting prolonged PR intervals slow-pathway ablation in elderly patients is both effective and safe and should be considered as the first line therapy also in this patient population
 

Catheter Ablation of Atrial Fibrillation Versus Atrioventricular Junction Ablation Plus Pacing Therapy for Elderly Patients with Medically Refractory Paroxysmal Atrial Fibrillation

Background: Catheter ablation of atrial fibrillation (AF) has become another nonpharmacologic therapeutic option for medically refractory paroxysmal AF. Whether this method is better than atrioventricular (AV) junction ablation plus pacing therapy is unknown. The purpose of this study was to compare the very long-term (longer than 4 years) clinical outcomes of the 2 methods in elderly patients (>65 years old) with medically refractory paroxysmal AF.
Methods: From January 1995 to December 2001, 71 elderly patients with medically refractory paroxysmal AF were included; group 1 included 32 patients with successful AV junction ablation plus pacing therapy and group 2, 37 patients with successful catheter ablation of AF.
Results: After a mean follow-up of more than 52 months, the AF was better controlled in the group 1 patients than group 2 (100% vs 81%, P = 0.013), however, they had a significantly higher incidence of persistent AF (69% vs 8%, P < 0.001) and heart failure (53% vs 24%, P = 0.001). Furthermore, the incidence of ischemic stroke and cardiac death was similar between the 2 groups. Compared with the preablation values, a significant increase in the NYHA functional class (1.7 ± 0.9 vs 1.4 ± 0.7, P = 0.01) and significant decrease in the left ventricular ejection fraction (44 ± 8% vs 51 ± 10%, P = 0.01) were noted in the group 1 patients, but not in the group 2 patients.
Conclusions: Although AV junction ablation plus pacing therapy better controlled the AF in elderly patients with medically refractory paroxysmal AF, that method was associated with a higher incidence of persistent AF and heart failure than catheter ablation of AF in the very long-term follow-up.
 

Long-Term Incidence of Malignant Ventricular Arrhythmia and Shock Therapy in Patients with Primary Defibrillator Implantation Does Not Differ from Event Rates in Patients Treated for Survived Cardiac Arrest

Introduction: Recent trials have demonstrated benefit of prophylactic defibrillator (ICD) implantation compared to conventional treatment in high-risk patients. However, many patients have rare or no sustained arrhythmias following implantation. Our study addresses the question, whether patients with prophylactic defibrillator implantation have a lower risk for life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) compared to sudden cardiac death (SCD) survivors.
Methods and Results: Over 7 years we enrolled 245 patients. Occurrence of spontaneous sustained VT/VF resulting in adequate ICD treatment was the endpoint. Incidence, type, and treatment of sustained arrhythmia in 43 previously asymptomatic ICD recipients (group B) were compared to data of 202 survivors of imminent SCD (group A). All patients had severely impaired left ventricular ejection fraction (<45%). Group B patients had long runs (>6 cycles, <30 s) of VT during Holter monitoring and inducible sustained arrhythmia. Incidence of rapid VT and VF (cycle length <240 ms/heart rate >250 bpm) after 4 years (35% in both groups, P = ns) and adequate defibrillator therapies (57% vs 55%, P = ns) were similar in both groups after univariate and multivariate analysis. Cumulative mortality tended to be lower in group B compared to group A, but the difference was not statistically significant.
Conclusion: During long-term follow-up, incidence of sustained rapid ventricular arrhythmia in prophylactically treated patients is as high as that of SCD survivors. Benefit from defibrillator implantation for primary prevention (group B) appears to be comparable to that for survived cardiac arrest (group A).
 

Effect of Concomitant Antiarrhythmic Therapy on Survival in Patients with Implantable Cardioverter Defibrillators

Background: Application of implantable cardioverter defibrillator (ICD) therapy is expanding to include both primary and secondary prevention of sudden cardiac death and has been proven to be superior to conventional antiarrhythmic therapies. Concomitant antiarrhythmic drug therapy in patients with ICD is common. These drugs are potentially proarrhythmic, alter defibrillation thresholds, and may affect response to device therapy. However, the impact of concomitant antiarrhythmic drug therapy on survival in patients with ICD devices is unknown.
Methods: We investigated the effect of different antiarrhythmic drugs on survival when given concomitantly in 360 consecutive ICD patients from our university medical center. Mortality data were obtained from the national death index. Survival analysis was performed using the Kaplan-Meier method. Corrections for significant covariates and group differences were made using the Cox regression model.
Results: Patients were followed up for 4.4 ± 3.7 years. There were 68 deaths over this period with a 5-year survival of 80%. Patient characteristics were: age 62 ± 13 years, left ventricular (LV) ejection fraction (EF) 33 ± 17%, ischemic etiology of LV dysfunction 68%, diabetes mellitus 19%, hypertension 49%, atrial fibrillation 23%, digoxin 43%, -blocker 46%, amiodarone 28%, and sotalol 9%. The use of -blockers was associated with a better survival (P = 0.0005). This effect persisted after correcting for age, heart rate, EF, and ischemic etiology. The beneficial effect of -blocker was unrelated to its effect on heart rate. Digoxin use was associated with a lower survival only on univariate analysis (P = 0.006), but not after adjusting for other variables on a Cox regression model (P = 0.093). Amiodarone and sotalol were found to have a neutral effect on survival.
Conclusion: In patients with ICDs, Beta-blockers had a favorable effect on survival. Sotalol and amiodarone had a neutral effect on survival. There was a trend toward a deleterious effect with digoxin use. These findings suggest a need for further investigation addressing survival effects of antiarrhythmic drugs when given concomitantly in patients with ICDs.

The Impact of Povidone-Iodine Pocket Irrigation Use on Pacemaker and Defibrillator Infections

Background: Infection is a devastating complication of permanent pacemakers (PMs) implantable cardioverter defibrillators (ICDs). Many implanting physicians commonly use povidone-iodine solution to irrigate the device pocket before implanting the device. We sought to assess if such a measure would alter the rate of infection.
Methods: A total of 2,564 consecutive patients who received implantable PM or ICD devices between 1994 and 2002 were studied. Povidone-iodine was used for pocket irrigation in 53% and saline in 47%. A total of 18 (0.7%) patients developed pocket infections with 0.7% (10/1,359) in povidone-iodine (group I) and 0.6% (8/1,205) in saline (group II) pocket irrigation (p = ns). Groups I and II were studied for various clinical and demographic variables described in the results section.
Results: There was no statistical difference in the baseline demographic and clinical characteristics between groups I and II, respectively. ICDs were most frequently infected than PMs (56% vs 44%). Most (83%) of the devices were dual chamber. Reopening of the pocket for either lead or generator replacement had a higher incidence of infection than new implants (61% vs 39%). There was no difference in the use of preimplantation antibiotic prophylaxis. Late (61%) and deep pocket infections (78%) were more common than early (39%) and superficial infections (22%). Blood cultures were positive in 67% and Staphylococcus aureus was the common most pathogen (50%). The mean duration of antibiotics use after the diagnosis of device infection was 35 ± 23 days with 72% requiring device explantation. The device was reimplanted on the contralateral side in 56% cases. One patient in each group died due to device infection and related complications. No significant allergy to iodine was seen in either group.
Conclusion: Povidone-iodine irrigation of the subcutaneous pocket did not alter the rates of pocket infection after pacemaker/defibrillator implantation.

Prevalence of Venous Obstruction in Permanent Endovenous Pacing in Newborns and Infants: Follow-Up Study

Objective: We examined the prevalence of venous obstruction in 12 newborns and infants with permanent endovenous ventricular pacing, clinically, and by ultrasonographic assessment of hemodynamics (spontaneity, phasicity, velocity, and turbulence of flow) and morphologic parameters (compressibility, wall thickness, and thrombus presence).
Material and Methods: All implantations of single ventricular unipolar endovenous steroid leads, were performed via cephalic vein, and pacemakers were placed in subcutaneous pocket in right prepectoral region. After the vascular surgeon has carefully examined all children for presence of venous collaterals in the chest wall, morphologic and hemodynamic parameters of the subclavian, axillary, and internal jugular veins, were assessed by linear-array color Doppler. Lead capacity (LC) was calculated for each patient.
Results: Mean age of patients at implant was 6.2 months (range 1 day 12 months), mean weight 6.5 kg (range 2.25 10 kg), and mean height 60.9 cm (range 48 78 cm). Mean LC was 1.99 (range 1.14 3.07). Total follow-up was 1023 and mean follow-up 85.2 pacing months (range 3 156). No clinical signs of venous obstruction were observed. Mild stenosis (20%) of subclavian vein was found by color Doppler in 2/12 patients. Both had adequate lead diameter for body surface.
Conclusion: Permanent endovenous pacing is a feasible procedure, even in children of body weight less than 10 kg, with quite acceptable impact on venous system patency.

Headache response to glyceryl trinitrate in patients with and without obstructive coronary artery disease

Objectives: To examine the hypothesis that glyceryl trinitrate (GTN) may cause headache in patients with normal coronary arteries more often than in patients with obstructive coronary artery disease (CAD). This simple assessment may aid clinicians in the initial evaluation of chest pain syndrome and possible CAD.
Patients and methods: 118 patients (66 men and 52 women) with new onset of chest pain were enrolled in this study. Patients were excluded from the study if they had a history of chronic headache, long term nitrates use, or any coronary artery procedures. Mean age of the patients was 62.5 years. Coronary angiography was performed within one month of GTN administration with the usual clinical indications such as recurrent chest pain, abnormal ECG, or abnormal results of stress tests. Thirty patients had normal coronary arteries or minimal or non-obstructive CAD. Eighty eight patients had obstructive CAD defined as luminal narrowing greater than 50% in any one or more of the left or right coronary arteries or their major branches. All the patients had a varying degree of relief of chest pain with GTN administration within 10 minutes. 36% of patients reported significant headache after GTN administration.
Results: In patients with normal coronary arteries or minimal CAD, 73% had significant headache caused by sublingual GTN. In patients with obstructive CAD, only 23% had significant headache after GTN use (p < 0.001). There were no differences in patients’ sex and vascular risk factors concerning the frequency of headache in patients with or without obstructive CAD.
Conclusions: GTN causes significantly more frequent headache episodes in patients with normal coronary arteries or minimal CAD than in patients with obstructive CAD. This unique finding may provide clinicians with an additional tool for the differential diagnosis of patients with chest pain syndrome.

Variable Electrocardiographic Effects of Short-Term Quinidine Sulfate Administration in Brugada Syndrome

Quinidine, a class I antiarrhythmic agent with blocking property of transient outward current, is a possible candidate for the suppression of ventricular fibrillation in patients with Brugada syndrome; although there is a concern that its ability to these effects may be proarrhythmic. Therefore, we evaluated the effect of quinidine sulfate on ST-segment elevation in Brugada syndrome. In 8 patients with Brugada syndrome, the magnitude of ST-elevation at the J-point (STJ), and the ST-segment configuration in leads V1 V3, were compared before and on day 2 after the initiation of quinidine administration. In 3 patients, quinidine attenuated STJ by 0.1 mV. Of these 3 patients, ST-segment elevation was normalized in 2 patients, while the ST-segment configuration was unchanged in another. In another 3 patients, quinidine augmented STJ by 0.1 mV without any change of ST-segment configuration, and the augmentation was returned to baseline after the discontinuation of quinidine. Quinidine exhibited no effect on the ST-segment in the remaining 2 patients. The favorable effects of quinidine on the ST-segment tended to be more pronounced in patients with prominent ST-elevation at baseline. In 1 patient, quinidine was effective in eliminating both ST-segment elevation and repetitive tachyarrhythmia episodes. In conclusion, the effects of quinidine on ST-segment elevation were variable. Quinidine may potentially augment the ST-segment elevation in some patients with Brugada syndrome.
 

"V-H-A Pattern" as a Criterion for the Differential Diagnosis of Atypical AV Nodal Reentrant Tachycardia from AV Reciprocating Tachycardia

Background: During ventricular extrastimulation, His bundle potential (H) following ventricular (V) and followed by atrial potentials (A), i.e., V-H-A, is observed in the His bundle electrogram when ventriculo-atrial (VA) conduction occurs via the normal conduction system. We examined the diagnostic value of V-H-A for atypical form of atrioventricular nodal reentrant tachycardia (AVNRT), which showed the earliest atrial activation site at the posterior paraseptal region during the tachycardia.
Methods: We prospectively examined the response of VA conduction to ventricular extrastimulation during basic drive pacing performed during sinus rhythm in 16 patients with atypical AVNRT masquerading atrioventricular reciprocating tachycardia (AVRT) utilizing a posterior paraseptal accessory pathway and 21 with AVRT utilizing a posterior paraseptal accessory pathway. Long RP' tachycardia with RP'/RR > 0.5 was excluded. The incidences of V-H-A and dual AV nodal physiology (DP) were compared between atypical AVNRT and AVRT.
Results: V-H-A was demonstrated in all the 16 patients (100%) in atypical AVNRT and in only 1 of the 21 (5%) in AVRT (P < 0.001). DP was demonstrated in 10 patients (63%) in atypical AVNRT and in 4 (19%) in AVRT (P < 0.05). The sensitivity of V-H-A for atypical AVNRT was higher than that of DP (P < 0.05). Positive and negative predictive values were 94% and 100%, respectively, for V-H-A and 71% and 74%, respectively, for DP.
Conclusions: The appearance of V-H-A during ventricular extrastimulation is a simple criterion for differentiating atypical AVNRT masquerading AVRT from AVRT utilizing a posterior paraseptal accessory pathway.

A national programme for on-site defibrillation by lay people in selected high risk areas: initial results

Objective: To report on the effectiveness of an initiative to reduce deaths from sudden cardiac arrest occurring in busy public places.
Setting: 110 such places identified from ambulance service data as high risk sites.
Patients: 172 members of the public who developed cardiac arrest at these sites between April 2000 and March 2004. 20 592 defibrillator months’ use is reported, representing one automated external defibrillator (AED) use every 120 months.
Intervention: 681 AEDs were installed; staff present at the sites were trained in basic life support and to use AEDs.
Main outcome measures: Initial rhythm detected by AED, restoration of spontaneous circulation, survival to hospital discharge.
Results: 172 cases of cardiac arrest were treated by trained lay staff working at the site before the arrival of the emergency services during the period. A shockable rhythm was detected in 135 (78%), shocks being administered in 134 an estimated 3–5 minutes after collapse; 38 (28.3%) patients subsequently survived to hospital discharge. Spontaneous circulation was restored in five additional patients who received shocks but died later in hospital. In 37 cases no shock was initially indicated; one patient survived after subsequent treatment by paramedics, cardiopulmonary resuscitation having been given soon after collapse. Overall, irrespective of the initial rhythm, 39 patients (22.7%), were discharged alive from hospital. For witnessed arrests of presumed cardiac cause in ventricular fibrillation (an international Utstein comparator) survival was 37 of 124 (29.8%).
Conclusions: The use of AEDs by lay people at sites where cardiac arrest commonly occurs is an effective strategy to reduce deaths at these sites.

Predictors of adverse outcome in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy: long term experience of a tertiary care centre

Objective: To investigate the predictors for adverse clinical outcome in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) during long term follow up.
Methods: 61 patients with ARVD/C were studied to assess the impact of family history, clinical findings, surface ECG parameters, echocardiographic findings, and electrophysiological findings on clinical outcome. The prevalence of these risk factors were compared in two patient groups: group A (patients with adverse clinical outcome: sudden cardiac death, death from heart failure, or heart transplant) and group B (survivors excluding patients who received a heart transplant).
Results: Mean age at first diagnosis was 44 (14) years. The mean follow up duration was 55 (47) months. Ten patients (16%) died during follow up. The cause of death of eight of these patients was probably arrhythmic. Two patients died of advanced heart failure. Five patients underwent heart transplantation because of terminal heart failure. Risk factors significantly associated with adverse outcome were history of congestive heart failure (p < 0.001), the presence of left ventricular involvement on echocardiography (p < 0.001), left atrial dilatation (p < 0.05), prolonged PR duration (p < 0.01), prolonged QRS in V1 (p < 0.05), and bundle branch block (p < 0.05). In multivariate analysis, history of congestive heart failure and presence of left ventricular involvement were identified as independent risk predictors for an adverse outcome.
Conclusions: Congestive heart failure and left ventricular involvement are independently associated with adverse outcome in patients with ARVD/C during long term follow up.

 

Sudden Unexplained Death. Heritability and Diagnostic Yield of Cardiological and Genetic Examination in Surviving Relatives

Background--Sudden death mostly follows from cardiac disorders that elicit lethal ventricular arrhythmias. In young individuals, it often remains unexplained because history and/or postmortem analysis are absent or provide no clue. Because such sudden unexplained deaths (SUDs) may have heritable causes, cardiological and genetic assessment of surviving relatives of SUD victims may reveal the underlying disease and unmask presymptomatic carriers. We aimed to establish the diagnostic yield of such assessments.
Methods and Results--We investigated 43 consecutive families with 1 SUD victim who died at 40 years of age. All studied relatives underwent resting/exercise ECG and Doppler echocardiography. Molecular genetic analysis was conducted to confirm the diagnosis. We identified an inherited disease and likely cause of death in 17 of 43 families (40%). Twelve families had primary electrical disease: catecholaminergic polymorphic ventricular tachycardia (5 families), long-QT syndrome (4 families), Brugada syndrome (2 families), and long-QT/Brugada syndrome (1 family). Furthermore, we found arrhythmogenic right ventricular cardiomyopathy (3 families), hypertrophic cardiomyopathy (1 family), and familial hypercholesterolemia (1 family). Molecular genetic analysis provided confirmation in 10 families. Finding the diagnosis was more likely when more relatives were examined and in families with 2 SUD victims 40 years of age. The resting/exercise ECG had a high diagnostic yield. These efforts unmasked 151 presymptomatic disease carriers (8.9 per family).
Conclusions--Examination of relatives of young SUD victims has a high diagnostic yield, with identification of the disease in 40% of families and 8.9 presymptomatic carriers per family. Simple procedures (examining many relatives) and routine tests (resting/exercise ECG) constitute excellent diagnostic strategies. Molecular genetics provide strong supportive information.

Outcome of 622 Adults With Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up

Background--This study assessed the long-term outcome of a large, asymptomatic population with hemodynamically significant aortic stenosis (AS).
Methods and Results--We identified 622 patients with isolated, asymptomatic AS and peak systolic velocity 4 m/s by Doppler echocardiography who did not undergo surgery at the initial evaluation and obtained follow-up (5.4±4.0 years) in all. Mean age (±SD) was 72±11 years; there were 384 (62%) men. The probability of remaining free of cardiac symptoms while unoperated was 82%, 67%, and 33% at 1, 2, and 5 years, respectively. Aortic valve area and left ventricular hypertrophy predicted symptom development. During follow-up, 352 (57%) patients were referred for aortic valve surgery and 265 (43%) patients died, including cardiac death in 117 (19%). The 1-, 2-, and 5-year probabilities of remaining free of surgery or cardiac death were 80%, 63%, and 25%, respectively. Multivariate predictors of all-cause mortality were age (hazard ratio [HR], 1.05; P<0.0001), chronic renal failure (HR, 2.41; P=0.004), inactivity (HR, 2.00; P=0.001), and aortic valve velocity (HR, 1.46; P=0.03). Sudden death without preceding symptoms occurred in 11 (4.1%) of 270 unoperated patients. Patients with peak velocity 4.5 m/s had a higher likelihood of developing symptoms (relative risk, 1.34) or having surgery or cardiac death (relative risk, 1.48).
Conclusions--Most patients with asymptomatic, hemodynamically significant AS will develop symptoms within 5 years. Sudden death occurs in 1%/y. Age, chronic renal failure, inactivity, and aortic valve velocity are independently predictive of all-cause mortality.

Long-Term Response to Calcium Channel Blockers in Idiopathic Pulmonary Arterial Hypertension Circulation

Background— Characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH) who benefit from long-term calcium channel blockers (CCB) are unknown.
Methods and Results— Acute pulmonary vasodilator testing with epoprostenol or nitric oxide was performed in 557 IPAH patients. Acute responders, defined by a fall in both mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) >20%, received long-term oral CCB. Patients who benefit from long-term CCB were defined as those being in New York Heart Association (NYHA) functional class I or II after at least 1 year on CCB monotherapy. Among the 70 patients who displayed acute pulmonary vasoreactivity (12.6%; 95% CI, 9.8% to 15.3%) and received CCB therapy, only 38 showed long-term improvement (6.8%; 95% CI, 4.7% to 8.9%). Long-term CCB responders had less severe disease at baseline than patients who failed. During acute vasodilator testing, long-term CCB responders displayed a more pronounced fall in mean PAP (–39±11% versus –26±7%; P<0.0001), reaching an absolute value of mean PAP lower than that measured in patients who failed (33±8 versus 46±10 mm Hg; P<0.0001). After 7.0±4.1 years, all but 1 long-term CCB responders were alive in NYHA class I or II, with a sustained hemodynamic improvement. In the group of patients who failed on CCB, the 5-year survival rate was 48%.
Conclusions— Long-term CCB responders represent <10% of IPAH patients evaluated in a pulmonary vascular referral center. During acute vasodilator testing, these patients showed significantly lower levels of both mean PAP and PVR, which reached near-normal values.




 

Right Atrial Pacing Impairs Cardiac Function During Resynchronization Therapy. Acute Effects of DDD Pacing Compared to VDD Pacing

Objectives We aimed to compare the hemodynamic effects of right-atrial-paced (DDD) and right-atrial-sensed (VDD) biventricular paced rhythm on cardiac resynchronization therapy (CRT).
Background Cardiac resynchronization therapy improves hemodynamics in patients with severe heart failure and left ventricular (LV) dyssynchrony. However, the impact of active right atrial pacing on resynchronization therapy is unknown.
Methods Seventeen CRT patients were studied 10 months (range: 1 to 46 months) after implantation. At baseline, the programmed atrioventricular delay was optimized by timing LV contraction properly at the end of atrial contraction. In both modes the acute hemodynamic effects were assessed by multiple Doppler echocardiographic parameters.
Results Compared to DDD pacing, VDD pacing resulted in much better improvement of intraventricular dyssynchrony assessed by the septal-to-posterior wall motion delay (VDD 106 ± 83 ms vs. DDD 145 ± 95 ms; p = 0.001), whereas the interventricular mechanical delay (difference between onset of pulmonary and aortic outflow) did not differ (VDD 20 ± 21 ms vs. DDD 18 ± 17 ms; p = NS). Furthermore, VDD pacing significantly prolonged the rate-corrected LV filling period (VDD 458 ± 123 ms vs. DDD 371 ± 94 ms; p = 0.0001) and improved the myocardial performance index (VDD 0.60 ± 0.18 vs. DDD 0.71 ± 0.23; p < 0.01).
Conclusions Our findings suggest that avoidance of right atrial pacing results in a higher degree of LV resynchronization, in a substantial prolongation of the LV filling period, and in an improved myocardial performance. Thus, the VDD mode seems to be superior to the DDD mode in CRT patients.
 

The Clinical Implications of Cumulative Right Ventricular Pacing in the Multicenter Automatic Defibrillator Trial II

Introduction: This study was designed to assess whether right ventricular pacing in the implantable cardioverter defibrillator (ICD) arm of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II was associated with an unfavorable outcome.
Methods and Results: Data on the number of ventricular paced beats were available in 567 (76%) of 742 MADIT II patients with ICDs. The number of ventricular paced beats over the total number of beats showed a bimodal distribution with patients being predominantly paced or nonpaced. Therefore, patients were dichotomized at 0 50% and 51 100% of cumulative pacing with median pacing rate 0.2% and 95.6%, respectively. Endpoints included new or worsening heart failure, appropriate ICD therapy for VT/VF, and the combined endpoint of heart failure or death. Clinical features associated with frequent ventricular pacing included age 65 years, advanced NYHA heart failure class, LVEF < 0.25, first degree AV and bundle branch block, and amiodarone use. During follow-up, 119 patients (21%) had new or worsened heart failure, 130 (23%) had new or worsened heart failure or death, and 142 (25%) had appropriate therapy for VT/VF. In comparison to patients with infrequent pacing, those with frequent pacing had significantly higher risk of new or worsened heart failure (hazard ratio = 1.93; P = 0.002) and VT/VF requiring ICD therapy (HR = 1.50; P = 0.02).
Conclusions: Patients in MADIT II who were predominantly paced had a higher rate of new or worsened heart failure and were more likely to receive therapy for VT/VF. These results suggest the deleterious consequences of RV pacing, particularly in the setting of severe LV dysfunction.
 

A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Adenosine as an Adjunct to Reperfusion in the Treatment of Acute Myocardial Infarction (AMISTAD-II)

Objectives The purpose of this research was to determine the effect of intravenous adenosine on clinical outcomes and infarct size in ST-segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy.
Background
Previous small studies suggest that adenosine may reduce the size of an evolving infarction.
Methods Patients (n = 2,118) with evolving anterior STEMI receiving thrombolysis or primary angioplasty were randomized to a 3-h infusion of either adenosine 50 or 70 μg/kg/min or of placebo. The primary end point was new congestive heart failure (CHF) beginning >24 h after randomization, or the first re-hospitalization for CHF, or death from any cause within six months. Infarct size was measured in a subset of 243 patients by technetium-99m sestamibi tomography.
Results There was no difference in the primary end point between placebo (17.9%) and either the pooled adenosine dose groups (16.3%) or, separately, the 50-μg/kg/min dose and 70-μg/kg/min groups (16.5% vs. 16.1%, respectively, p = 0.43). The pooled adenosine group trended toward a smaller median infarct size compared with the placebo group, 17% versus 27% (p = 0.074). A dose-response relationship with final median infarct size was seen: 11% at the high dose (p = 0.023 vs. placebo) and 23% at the low dose (p = NS vs. placebo). Infarct size and occurrence of a primary end point were significantly related (p < 0.001).
Conclusions Clinical outcomes in patients with STEMI undergoing reperfusion therapy were not significantly improved with adenosine, although infarct size was reduced with the 70-μg/kg/min adenosine infusion, a finding that correlated with fewer adverse clinical events. A larger study limited to the 70-μg/kg/min dose is, therefore, warranted.




 

Patients With Atrial Fibrillation and Dense Spontaneous Echo Contrast at High Risk. A Prospective and Serial Follow-Up Over 12 Months With Transesophageal Echocardiography and Cerebral Magnetic Resonance Imaging

Objectives We sought to assess the prognosis of patients with atrial fibrillation (AF) and dense spontaneous echo contrast (SEC) and to determine the incidence of cerebral embolism under continued oral anticoagulation.
Background Patients with AF and dense SEC have an increased risk of cerebral embolism. However, there is little knowledge about the long-term fate and the rate of clinical silent cerebral embolism under continued oral anticoagulation.
Methods Between 1998 and 2001, all consecutive patients with AF and dense SEC were included in the study. We performed serial and prospective transesophageal echocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 12 months.
Results A total of 128 patients with dense SEC and AF were included. The control group consisted of 143 patients with faint SEC and AF. During the follow-up period, three patients (2%) had cerebral embolism with neurologic deficits. A total of eight patients (6%) died due to embolic events, and 19 (15%) patients had silent embolism, as documented on cerebral magnetic resonance imaging. Patients with an event had significantly lower left atrial appendage peak emptying velocities and more commonly had a history of previous thromboembolism and denser SEC, as compared with patients without an event.
Conclusions Patients with AF and dense SEC have a high likelihood of cerebral embolism (22%) and/or death, despite oral anticoagulation. Low peak emptying velocities of the left atrial appendage and dense SEC are independent predictors of an event.




 

Catheter Ablation of Atrial Fibrillation Versus Atrioventricular Junction Ablation Plus Pacing Therapy for Elderly Patients with Medically Refractory Paroxysmal Atrial Fibrillation

Background: Catheter ablation of atrial fibrillation (AF) has become another nonpharmacologic therapeutic option for medically refractory paroxysmal AF. Whether this method is better than atrioventricular (AV) junction ablation plus pacing therapy is unknown. The purpose of this study was to compare the very long-term (longer than 4 years) clinical outcomes of the 2 methods in elderly patients (>65 years old) with medically refractory paroxysmal AF.
Methods: From January 1995 to December 2001, 71 elderly patients with medically refractory paroxysmal AF were included; group 1 included 32 patients with successful AV junction ablation plus pacing therapy and group 2, 37 patients with successful catheter ablation of AF.
Results: After a mean follow-up of more than 52 months, the AF was better controlled in the group 1 patients than group 2 (100% vs 81%, P = 0.013), however, they had a significantly higher incidence of persistent AF (69% vs 8%, P < 0.001) and heart failure (53% vs 24%, P = 0.001). Furthermore, the incidence of ischemic stroke and cardiac death was similar between the 2 groups. Compared with the preablation values, a significant increase in the NYHA functional class (1.7 ± 0.9 vs 1.4 ± 0.7, P = 0.01) and significant decrease in the left ventricular ejection fraction (44 ± 8% vs 51 ± 10%, P = 0.01) were noted in the group 1 patients, but not in the group 2 patients.
Conclusions: Although AV junction ablation plus pacing therapy better controlled the AF in elderly patients with medically refractory paroxysmal AF, that method was associated with a higher incidence of persistent AF and heart failure than catheter ablation of AF in the very long-term follow-up.

Severe Symptomatic Tricuspid Valve Regurgitation Due to Permanent Pacemaker or Implantable Cardioverter-Defibrillator Leads

Objectives We report a series of patients with severe tricuspid valve regurgitation due to a permanent pacemaker (PPM) or implantable cardioverter-defibrillator (ICD) lead.
Background Severe tricuspid regurgitation caused by a PPM or ICD lead is an under-recognized but treatable etiology of severe right heart failure.
Methods We reviewed the records of 41 patients who underwent tricuspid valve operation for severe tricuspid regurgitation caused by previously placed PPM or ICD leads.
Results During surgery, severe tricuspid regurgitation was found to be caused by the PPM or ICD leads in all 41 patients. There was a perforation of the tricuspid valve leaflet by the PPM or ICD lead in 7 patients, lead entanglement in the tricuspid valve occurred in 4 patients, lead impingement of the tricuspid valve leaflets occurred in 16 patients, and lead adherence to the tricuspid valve occurred in 14 patients. The septal leaflet was most often perforated (6 of 7). In the preoperative evaluation, valve malfunction due to the PPM or ICD lead was diagnosed preoperatively in only 5 of 41 (12%) patients by transthoracic echocardiography. All patients underwent successful tricuspid valve operation (22 tricuspid valve replacement), with one perioperative death occurring. During follow-up (range, 1 to 99 months), there was one patient who died from left-sided heart failure and three patients died of other causes. The remaining patients showed improvement in signs and symptoms of heart failure.
Conclusions Damage to the tricuspid valve by PPM or ICD leads may result in severe symptomatic tricuspid regurgitation and may not be overtly visualized by echocardiography. This etiology should be considered when evaluating patients with severe right heart failure after PPM or ICD implantation.


 

Relationship Between Successful Ablation Sites and the Scar Border Zone Defined by Substrate Mapping for Ventricular Tachycardia Post-Myocardial Infarction

Introduction: It is unknown if identification of scar border zones by electroanatomical mapping correlates with successful ablation sites determined from mapping during ventricular tachycardia (VT) post-myocardial infarction (MI). We sought to assess the relationship between successful ablation sites of hemodynamically stable post-MI VTs determined by mapping during VT with the scar border zone defined in sinus rhythm.
Methods and Results: Forty-six patients presenting with hemodynamically stable, mappable monomorphic VT post-MI and who had at least one such VT successfully ablated were prospectively included in the study. In each patient, VT was ablated by targeting regions during VT that exhibited early activation, ± isolated mid-diastolic potentials, and concealed entrainment suggesting a critical isthmus site. Prior to ablation, a detailed sinus-rhythm CARTO voltage map of the left ventricle was obtained. A voltage <0.5 mV defined dense scar. Successful VT ablation sites were registered on the sinus voltage map to assess their relationship to the scar border zone. Of the 86 VTs, 68% were successfully ablated at sites in the endocardial border zone. The remaining VTs had ablation sites within the scar in (18%), in normal myocardium (4%), and on the epicardial surface (10%). There were no significant differences in VT recurrence amongst the different groups.
Conclusion: Successful ablation sites of hemodynamically stable, monomorphic VTs post-MI are often located in the scar border zone as defined by substrate voltage mapping. However, in a sizable minority, ablation sites are located within endocardial scar, epicardially, and even in normal myocardium.


 

A Randomized Trial of Intensive Lipid-Lowering Therapy in Calcific Aortic Stenosis

Background Calcific aortic stenosis has many characteristics in common with atherosclerosis, including hypercholesterolemia. We hypothesized that intensive lipid-lowering therapy would halt the progression of calcific aortic stenosis or induce its regression.
Methods In this double-blind, placebo-controlled trial, patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo. Aortic-valve stenosis and calcification were assessed with the use of Doppler echocardiography and helical computed tomography, respectively. The primary end points were change in aortic-jet velocity and aortic-valve calcium score.
Results Seventy-seven patients were assigned to atorvastatin and 78 to placebo, with a median follow-up of 25 months (range, 7 to 36). Serum low-density lipoprotein cholesterol concentrations remained at 130±30 mg per deciliter in the placebo group and fell to 63±23 mg per deciliter in the atorvastatin group (P<0.001). Increases in aortic-jet velocity were 0.199±0.210 m per second per year in the atorvastatin group and 0.203±0.208 m per second per year in the placebo group (P=0.95; adjusted mean difference, 0.002; 95 percent confidence interval, –0.066 to 0.070 m per second per year). Progression in valvular calcification was 22.3±21.0 percent per year in the atorvastatin group, and 21.7±19.8 percent per year in the placebo group (P=0.93; ratio of post-treatment aortic-valve calcium score, 0.998; 95 percent confidence interval, 0.947 to 1.050).
Conclusions Intensive lipid-lowering therapy does not halt the progression of calcific aortic stenosis or induce its regression. This study cannot exclude a small reduction in the rate of disease progression or a significant reduction in major clinical end points. Long-term, large-scale, randomized, controlled trials are needed to establish the role of statin therapy in patients with calcific aortic stenosis.

Radiofrequency Ablation vs Antiarrhythmic Drugs as First-line Treatment of Symptomatic Atrial Fibrillation
A Randomized Trial

Context Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation (AF). Pulmonary vein isolation (PVI) with radiofrequency ablation may cure AF, obviating the need for antiarrhythmic drugs and anticoagulation.
Objective To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF.
Design, Setting, and Participants A multicenter prospective randomized study conducted from December 31, 2001, to July 1, 2002, of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs.
Intervention Patients were randomized to receive either PVI using radiofrequency ablation (n=33) or antiarrhythmic drug treatment (n=37), with a 1-year follow-up.
Main Outcome Measures Recurrence of AF, hospitalization, and quality of life assessment.
Results Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up. At the end of 1-year follow-up, 22 (63%) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4 (13%) of 32 patients who received PVI (P<.001). Hospitalization during 1-year follow-up occurred in 19 (54%) of 35 patients in the antiarrhythmic drug group compared with 3 (9%) of 32 in the PVI group (P<.001). In the antiarrhythmic drug group, the mean (SD) number of AF episodes decreased from 12 (7) to 6 (4), after initiating therapy (P = .01). At 6-month follow-up, the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey. There were no thromboembolic events in either group. Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2 (6%) of 32 patients in the PVI group.
Conclusion Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF. Larger studies are needed to confirm its safety and efficacy.




 

Long-Term Incidence of Malignant Ventricular Arrhythmia and Shock Therapy in Patients with Primary Defibrillator Implantation Does Not Differ from Event Rates in Patients Treated for Survived Cardiac Arrest

Introduction: Recent trials have demonstrated benefit of prophylactic defibrillator (ICD) implantation compared to conventional treatment in high-risk patients. However, many patients have rare or no sustained arrhythmias following implantation. Our study addresses the question, whether patients with prophylactic defibrillator implantation have a lower risk for life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) compared to sudden cardiac death (SCD) survivors.
Methods and Results: Over 7 years we enrolled 245 patients. Occurrence of spontaneous sustained VT/VF resulting in adequate ICD treatment was the endpoint. Incidence, type, and treatment of sustained arrhythmia in 43 previously asymptomatic ICD recipients (group B) were compared to data of 202 survivors of imminent SCD (group A). All patients had severely impaired left ventricular ejection fraction (<45%). Group B patients had long runs (>6 cycles, <30 s) of VT during Holter monitoring and inducible sustained arrhythmia. Incidence of rapid VT and VF (cycle length <240 ms/heart rate >250 bpm) after 4 years (35% in both groups, P = ns) and adequate defibrillator therapies (57% vs 55%, P = ns) were similar in both groups after univariate and multivariate analysis. Cumulative mortality tended to be lower in group B compared to group A, but the difference was not statistically significant.
Conclusion: During long-term follow-up, incidence of sustained rapid ventricular arrhythmia in prophylactically treated patients is as high as that of SCD survivors. Benefit from defibrillator implantation for primary prevention (group B) appears to be comparable to that for survived cardiac arrest (group A).
 

The effect of prophylactic topical steroid cream on the incidence and severity of cutaneous burns following external DC cardioversion

Introduction: Cutaneous burns are a common cause of morbidity following direct current (DC) cardioversion. We designed a prospective double-blinded controlled study to determine whether the application of steroid cream prior to cardioversion reduces their incidence and severity.
Materials and methods: Two hours before elective DC cardioversion, we applied betamethasone 0.1% cream or placebo cream over sternal and apical pad sites in 56 patients, with patients acting as their own controls. Two hours after cardioversion, a separate blinded observer measured the visual analogue pain score (VAS), sensory and pain detection thresholds, skin temperature and erythema index at sternal and apical pad sites.
Results: The study had an 80% power to detect a 50% difference in VAS at 2 h, accepting an α error of 0.05. There was no difference between pain at 2 or 24 h, skin temperature, erythema index, sensory and pain detection thresholds at pad sites treated with steroid cream or control.
Conclusion: Topical betamethasone 0.1% cream applied 2 h before elective DC cardioversion is no more effective than placebo at reducing the pain and inflammation from cardioversion burns.


 

Association of Prolonged QRS Duration With Death in a Clinical Trial of Pacemaker Therapy for Sinus Node Dysfunction

Background--Prolonged QRS duration (QRSd) is an important prognostic indicator for death and heart failure hospitalization in patients with systolic heart failure. The relationship of baseline QRSd to death and heart failure hospitalization in patients with sinus node dysfunction who require pacemaker therapy is unknown.
Methods and Results--Baseline QRSd from 12-lead ECGs before pacemaker implantation were analyzed in the Mode Selection Trial (MOST), a 6-year, 2010-patient randomized trial of dual-chamber versus ventricular pacing in sinus node dysfunction. Baseline QRSd was 120 ms in 23.4% of patients and was associated with older age, lower ejection fraction, cardiomyopathy, and prior heart failure. Adjusted Cox models demonstrated baseline QRSd 120 ms was a strong independent predictor of death (hazard ratio [95% CI] 1.35 [1.07, 1.70], P=0.010) but not heart failure hospitalization. The risk of death increased with increased QRSd from 60 to 120 ms (P=0.002 and hazard ratio [95% CI] 1.14 [1.05, 1.23] for 10-ms increase in this range) after adjustment for other death predictors.
Conclusions--Baseline QRSd 120 ms was associated with increased risk of death during pacemaker therapy for sinus node dysfunction.




 

Amiodarone versus Sotalol for Atrial Fibrillation

Background The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial.
Methods In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring.
Results Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial f ibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups.
Conclusions Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.

 

Infarct morphology identifies patients with substrate for sustained ventricular tachycardia

Objectives We sought to evaluate whether infarct size characterization by cardiac magnetic resonance imaging (MRI) is a better predictor of inducible ventricular tachycardia (VT) than left ventricular ejection fraction (LVEF).
Background Inducibility of VT at electrophysiologic study (EPS) and low LVEF can identify patients with a substrate for VT. Magnetic resonance imaging has been shown to identify, with high precision, areas of myocardial infarction and may therefore be a better tool to evaluate for a substrate for VT.
Methods We studied 48 patients with known coronary artery disease who were referred for EPS using cine and gadolinium-enhanced MRI. Wall motion and infarct characteristics were determined blindly and compared among patients with no inducible ventricular arrhythmias (n = 21), those with inducible monomorphic VT (MVT, n = 18), and those with either inducible polymorphic VT or ventricular fibrillation (n = 9).
Results Patients with MVT had larger infarcts than patients who did not have inducible arrhythmias (mass: 49 ± 5 g [SE] vs. 28 ± 5 g, p < 0.005; surface area: 172 ± 15 cm2 vs. 93 ± 14 cm2, p < 0.0005). Patients with polymorphic VT/fibrillation had intermediate values (mass: 36 ± 7 g; surface area: 115 ± 22 cm2). Ejection fraction was inversely related to infarct mass and surface area, with R2 values ranging from 0.21 to 0.27. Logistic regression and receiver-operating characteristic analysis demonstrated that infarct mass and surface area were better predictors of inducibility of MVT than LVEF.
Conclusions Infarct surface area and mass, as measured by cardiac MRI, are better identifiers of patients who have a substrate for MVT than LVEF. Further evaluation of infarct size characterization by cardiac MRI as a predictor of sudden cardiac death is warranted.
 

Early initiation of lipid-lowering therapy for acute coronary syndromes improves compliance with guideline recommendations: Observations from the Orbofiban in Patients with Unstable Coronary Syndromes (OPUS–TIMI 16) trial

Background Lipid-lowering is effective in the prevention of cardiovascular morbidity and mortality in patients with coronary artery disease, but effective strategies for improving the implementation of these therapies are needed.

Methods In the 10288 patients in the OPUS–TIMI 16 trial, patients were stratified by use of lipid-lowering therapy during index hospitalization and were compared for use of lipid-lowering therapy at follow-up as well as for clinical outcomes.

Results Lipid-lowering therapy was used in 38% of patients during the index hospitalization, of which 94% were statins. At 10 months, 88% of patients who were discharged on lipid-lowering medications remained on these drugs. Conversely, only 34% of patients not discharged on lipid-lowering medications were receiving them at 10 months. Forty-one percent of patients with prior history of hyperlipidemia requiring treatment were not discharged on lipid-lowering therapy, and of these, only 51% were subsequently started on a lipid-lowering medication as an outpatient despite clear indications. Patients treated as inpatients with lipid-lowering therapy had a lower mortality rate at 10 months adjusted by propensity analysis (3.1% vs 5.1%, P < .0001) than patients not treated with lipid-lowering therapy.

Conclusion In patients with acute coronary syndromes, the initiation of lipid-lowering therapy in the inpatient setting increases the rate of its subsequent use at 10 months, making this an important method of ensuring appropriate secondary prevention.





 

Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: The Vytorin Versus Atorvastatin (VYVA) Study

Background Low-density lipoprotein cholesterol (LDL-C) is the primary therapeutic target in the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines. This study tested the hypothesis that ezetimibe/simvastatin, a lipid-lowering agent that inhibits both intestinal cholesterol absorption and cholesterol synthesis, provides greater LDL-C reductions than atorvastatin across dose ranges.

Methods This multicenter, double-blind, 6-week parallel-group study randomized 1902 patients with LDL-C above ATP III goal to atorvastatin (10, 20, 40, or 80 mg) or to ezetimibe/simvastatin (10/10, 10/20, 10/40, or 10/80 mg). Patients were stratified by prerandomization LDL-C level.

Results At each milligram-equivalent statin dose comparison, and averaged across doses, ezetimibe/simvastatin provided greater LDL-C reductions (47%-59%) than atorvastatin (36%-53%). Ezetimibe/simvastatin 10/40 and 10/80 mg also provided significantly greater high-density lipoprotein cholesterol (HDL-C) increases than atorvastatin 40 and 80 mg. Triglyceride reductions were similar for all comparisons. More ezetimibe/simvastatin than atorvastatin patients with coronary heart disease (CHD) or CHD risk equivalents attained the ATP III LDL-C goal of <100 mg/dL and the optional LDL-C target of <70 mg/dL. C-reactive protein reductions were similar between treatment groups. Consecutive elevations in alanine aminotransferase and/or aspartate aminotransferase occurred in significantly more atorvastatin patients than ezetimibe/simvastatin patients. No myopathy or liver-related adverse events led to study discontinuation with either drug.

Conclusions Ezetimibe/simvastatin was more effective than atorvastatin in lowering LDL-C at each dose comparison and provided greater increases in HDL-C at the 40- and 80-mg statin dose. Ezetimibe/simvastatin is a highly efficacious, well-tolerated treatment option for hypercholesterolemic patients.



 

Arrhythmogenic right ventricular dysplasia Echocardiographic findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia New insights from the multidisciplinary study of right ventricular dysplasia

Objectives The purpose of this study was to quantify the echocardiographic abnormalities in probands who were newly diagnosed with arrhythmogenic right ventricular dysplasia (ARVD).
Background The diagnosis of ARVD remains challenging. The Multidisciplinary Study of Right Ventricular Dysplasia was initiated to characterize the cardiac structural, clinical, and genetic aspects of ARVD.
Methods Detailed echocardiograms were performed in 29 probands and compared with echoes from 29 normal control patients matched for age, gender, body size, and year of echo. Right atrial (RA) and right ventricular (RV) chamber dimensions, RV regional function, and the presence of morphologic abnormalities (hyper-reflective moderator band, trabecular derangement, and sacculations) were assessed. The RV systolic function was calculated as RV fractional area change (FAC).
Results The RV dimensions were significantly increased, and RV FAC was significantly decreased in probands versus control patients (27.2 ± 16 mm vs. 41.0 ± 7.1 mm, p = 0.0003). The right ventricular outflow tract (RVOT) was the most commonly enlarged dimension in ARVD probands (37.9 ± 6.6 mm) versus control patients (26.2 ± 4.9 mm, p < 0.00001). A RVOT long-axis diastolic dimension >30 mm occurred in 89% of probands and 14% of controls. The RV morphologic abnormalities were present in many probands (trabecular derangement in 54%, hyper-reflective moderator band in 34% and sacculations in 17%) but not in controls.
Conclusions Probands with ARVD have significant RA and RV enlargement and decreased RV function, which can be easily assessed on standard echocardiographic imaging. These parameters should be measured when ARVD is suspected and compared with normal values.

 

Idiopathic ventricular arrhythmia arising from the mitral annulus A distinct subgroup of idiopathic ventricular arrhythmias

Objectives We sought to clarify the prevalence and characteristics of idiopathic ventricular tachycardia or premature ventricular contraction originating from the mitral annulus (MAVT/PVC).
Background Recent case reports have presented patients with MAVT/PVC.
Methods Electrocardiographic (ECG) characteristics and the results of electrophysiologic investigation and radiofrequency catheter ablation (RFCA) were analyzed in 352 patients with symptomatic idiopathic ventricular tachycardia (IVT)/premature ventricular contraction (PVC).
Results Nineteen cases of IVT/PVC (5%) represented MAVT/PVC. Of these, 11 (58%) originated from the anterolateral portion of the mitral annulus (AL-MAVT/PVC), and 2 (11%) arose from the posterior portion (Pos-MAVT/PVC). The remaining six cases of MAVT/PVC (31%) had posteroseptal origin (PS-MAVT/PVC). In all patients, an S-wave was present in lead V6. The QRS polarity in inferior leads and leads I and aVL was useful for differentiating AL-MAVT/PVC from Pos-MAVT/PVC or PS-MAVT/PVC. The Pos-MAVT/PVC had an Rs pattern in lead I and an R pattern in lead V1, whereas PS-MAVT/PVC invariably had an R pattern in lead I and a negative QRS component in lead V1. The AL-MAVT/PVC and Pos-MAVT/PVC showed a longer QRS duration than the PS-MAVT/PVC (p < 0.001), and all had late-phase “notching” of the QRS complex in inferior leads. In all patients, RFCA eliminated MAVT/PVC, with no recurrences during follow-up for 21 ± 15 months.
Conclusions Mitral annular VT/PVC is a rare but distinct subgroup of IVT/PVC. MAVT/PVC origin could be determined by ECG analysis. The AL and PS sites of the MA were preferential.

Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: Results from the Canadian Registry of Atrial Fibrillation

Background After its initial diagnosis, atrial fibrillation (AF) may progress from paroxysmal to chronic AF (CAF). The rate of progression and risk factors for progression are not clearly defined.

Methods The Canadian Registry of Atrial Fibrillation (CARAF) enrolled patients from 6 Canadian cities at the time of their first electrocardiographic diagnosis of AF. Comprehensive clinical and echocardiographic data were collected and patients were followed annually, carefully documenting clinical outcomes, recurrence of paroxysmal AF, and progression to CAF. Baseline clinical, electrocardiographic, and echocardiographic variables were evaluated by univariate Cox proportionate hazards analysis. A stepwise approach was used to model the association between echocardiographic and clinical variables with progression to CAF.

Results A total of 757 patients with a baseline diagnosis of paroxysmal AF were evaluated. Median follow-up was 8.0 years (range 2 days to 11.1 years). The probability of progression to CAF by 1 year was 8.6% and thereafter there was a slow but steady progression to 24.7% by 5 years. By 5 years, the probability of documented recurrence of any AF (chronic or paroxysmal) was 63.2%. Increasing age, significant aortic stenosis or mitral regurgitation, left atrial enlargement, and diagnosis of cardiomyopathy were independently associated with progression to CAF. A more rapid heart rate during AF was associated with decreased risk of progression.

Conclusions After the initial diagnosis of paroxysmal AF, there is a slow but steady progression to CAF. Baseline echocardiographic variables, age, cardiomyopathy, and heart rate were independently associated with progression to CAF.
 

Functional impact of rate irregularity in patients with heart failure and atrial fibrillation receiving cardiac resynchronization therapy

Aims Atrial fibrillation (AFib) with a rapid ventricular response may adversely impact cardiac performance, especially in patients with heart failure. However, it remains uncertain whether rhythm irregularity per se has unfavourable effects apart from tachycardia, and whether rate regularization alone can improve heart function.
Methods and results Nine subjects with chronic AFib, atrioventricular nodal block, and symptomatic heart failure (ejection fraction 14–30%) were studied using a pressure–volume catheter. Ventricles were biventricularly paced (RV-apex, LV-lateral wall) at 80 or 120 min–1 mean rate, using regular or irregular, Poisson-distributed stimulation. At 80 min–1, ventricular function was similar between the two pacing modes. However, at 120 min–1, irregular pacing impaired systolic (dP/dtmax: –8.2%, P<0.001) and diastolic function (dP/dtmin: +21%, P<0.001, LV end-diastolic pressure: +26%, P=0.007) compared with regular rate pacing. Contractile function during irregular pacing varied with the ratio of preceding/pre-preceding intercycle (RR) interval (dP/dtmax: 80 b.p.m.: r=0.69; 120 b.p.m.: r=0.74), whereas pre-load had little effect on instantaneous contractility.
Conclusion In heart failure subjects with AFib, RR-interval irregularity worsens cardiac function at elevated but not at normal range heart rate. Overall rate control is most important in these patients while rate regularization of rapid AFib may impart additional benefits.
 

Prediction of sudden cardiac death after acute myocardial infarction: role of Holter monitoring in the modern treatment era

Aims Current treatment may have changed the risk profiles of survivors of acute myocardial infarction (AMI). We evaluated the utility of Holter-based risk variables in the prediction of sudden cardiac death (SCD) among survivors of AMI treated with modern therapy.
Methods and results A total of 2130 AMI patients (mean age 59±10 years) were included. The patients were treated with modern therapeutic strategies, for example, 94% were on ß-blocking therapy and 70% underwent coronary revascularization. Various risk parameters from Holter monitoring were analysed. During a median follow-up of 1012 days (interquartile range: 750–1416 days), cardiac mortality was 113/2130, including 52 SCDs. All Holter variables predicted the occurrence of SCD (P<0.01), but only reduced post-ectopic turbulence slope (TS) (P<0.001) and non-sustained ventricular tachycardia (P<0.01) remained as marked SCD predictors after adjustment for age, diabetes, and ejection fraction (EF). In a subgroup analysis, none of the Holter variables predicted SCD among those with an EF 0.35, but many variables predicted SCD among those with an EF >0.35, particularly TS (hazard ratio 5.9; 95% CI 2.9–11.7, P<0.001).
Conclusion Among the post-AMI patients treated according to the current guidelines, the incidence of SCD is low. Various Holter variables still predict the occurrence of SCD, particularly among the patients with preserved left ventricular function.

 

Incidence, predictors, and outcomes of high-degree atrioventricular block complicating acute myocardial infarction treated with thrombolytic therapy

Background In the fibrinolytic era, several studies have suggested that the rate of atrioventricular block (AVB) in the setting of acute myocardial infarction (MI) is high and is associated with increased short-term mortality. We sought to delineate predictors of AVB and determine long-term mortality of patients developing AVB in the setting of ST-segment elevation MI (STEMI) treated with thrombolytic therapy.

Methods We combined data on patients from 4 similar studies of STEMI. We identified independent predictors of AVB and compared the 6-month and 1-year mortality rates of patients with AVB (5251) to the rates of patients without AVB (70742).

Results The incidence of AVB was 6.9%. Significant independent predictors of AVB included inferior MI, older age, worse Killip class at presentation, female sex, enrollment in the United States, current smoking, hypertension, and diabetes. Adjusted mortality was significantly higher in patients with AVB than in patients without AVB within 30 days (OR 3.2, 95% CI 2.7-3.7), 6 months (OR 1.6, 95% CI 1.5-1.8), and 1 year (OR 1.5, 95% CI 1.3-1.6). For patients with AVB and inferior MI, mortality odds ratios (ORs) were 2.2 (95% CI 1.7-2.7), 2.6 (95% CI 2.4-2.9), and 2.4 (95% CI 2.2-2.6) within 30 days, 6 months, and 1 year, respectively. For patients with AVB and anterior MI, mortality ORs were 3.0 (95% CI 2.2-4.1), 3.5 (95% CI 3.1-3.8), and 3.3 (95% CI 3.0-3.7) within 30 days, 6 months, and 1 year, respectively.

Conclusions In the thrombolytic era, AVB in the setting of STEMI is common and associated with higher mortality. Future studies should focus on determining therapies that are effective at reducing mortality rates in such patients.
 

Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilation and clinical status in patients without structural heart disease

Objectives The present study evaluated clinical benefits of radiofrequency catheter ablation (RFA) for premature ventricular complexes from right ventricular outflow tract (RVOT-PVC) in patients without structural heart disease.
Background It is unknown whether PVC causes left ventricular (LV) dilation, which is a well-recognized precursor of LV dysfunction and heart failure, and whether eliminating PVC by RFA produces clinical benefits in patients with RVOT-PVC.
Methods Frequency of PVC per total heart beats by 24-h Holter monitoring, left ventricular ejection fraction (LVEF), left ventricular end-diastolic internal dimension (LVDd), mitral regurgitation (MR) by echocardiogram, cardiothoracic ratio (CTR) by chest radiogram, and New York Heart Association (NYHA) functional class of 40 patients with RVOT-PVC without structural heart disease were evaluated before and 6 to 12 months after RFA.
Results Before RFA, a subgroup of patients with frequent (>20%) PVC demonstrated significantly enlarged LVDd and CTR, reduced LVEF, increased MR, and deteriorated NYHA functional class as compared to the subgroup with rare (<20%) PVC (54 ± 1 mm vs. 45 ± 1 mm, 52 ± 2% vs. 46 ± 1%, 66 ± 2% vs. 73 ± 2%, 1.2 ± 0.2 degree vs. 0.4 ± 0.1 degree, and 1.8 ± 0.2 vs. 1.3 ± 0.1, respectively; p < 0.05). Furthermore, ablating RVOT-PVC readily produced the improvement of all these abnormalities (47 ± 1 mm, 41 ± 1%, 72 ± 2%, 0.3 ± 0.1 degree, and 1.0 ± 0.0, respectively; p < 0.05 compared with before RFA).
Conclusions These findings suggest that frequent (>20%) RVOT-PVC may be a possible cause of LV dysfunction and/or heart failure, and RFA produces clinical benefits in these patients.

Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fibrillation

Aims Left ventricular (LV) and biventricular (BiV) pacing are potentially superior to right ventricular (RV) apical pacing in patients undergoing atrioventricular (AV) junction ablation and pacing for permanent atrial fibrillation.
Methods and results Prospective randomized, single-blind, 3-month crossover comparison between RV and LV pacing (phase 1) and between RV and BiV pacing (phase 2) performed in 56 patients (70±8 years, 34 males) affected by severely symptomatic permanent atrial fibrillation, uncontrolled ventricular rate, or heart failure. Primary endpoints were quality of life and exercise capacity. Compared with RV pacing, the Minnesota Living with Heart Failure Questionnaire (LHFQ) score improved by 2 and 10% with LV and BiV pacing, respectively, the effort dyspnoea item of the Specific Symptom Scale (SSS) changed by 0 and 2%, the Karolinska score by 6 and 14% (P<0.05 for BiV), the New York Heart Association (NYHA) class by 5 and 11% (P<0.05 for BiV), the 6-min walked distance by 12 (+4%) and 4 m (+1%), and the ejection fraction by 5 and 5% (P<0.05 for both). BiV pacing but not LV pacing was slightly better than RV pacing in the subgroup of patients with preserved systolic function and absence of native left bundle branch block. Compared with pre-ablation measures, the Minnesota LHFQ score improved by 37, 39, and 49% during RV, LV, and BiV pacing, respectively, the effort dyspnoea item of the SSS by 25, 25, and 39%, the Karolinska score by 39, 42, and 54%, the NYHA class by 21, 25, and 30%, the 6-min walking distance by 35 (12%), 47 (16%), and 51 m (19%) and the ejection fraction by 5, 10, and 10% (all differences P<0.05).
Conclusions Rhythm regularization achieved with AV-junction ablation improved quality of life and exercise capacity with all modes of pacing. LV and BiV pacing provided modest or no additional favourable effect compared with RV pacing.

 

Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population

Objective: To evaluate how well patients with non-valvar atrial fibrillation (NVAF) were maintained within the recommended international normalised ratio (INR) target of 2.0–3.0 and to explore the relation between achieved INR control and clinical outcomes.
Design: Record linkage study of routine activity records and INR measurements.
Setting: Cardiff and the Vale of Glamorgan, South Wales, UK.
Participants: 2223 patients with NVAF, no history of heart valve replacement, and with at least five INR measurements.
Main outcome measures: Mortality, ischaemic stroke, all thromboembolic events, bleeding events, hospitalisation, and patterns of INR monitoring.
Results: Patients treated with warfarin were outside the INR target range 32.1% of the time, with 15.4% INR values > 3.0 and 16.7% INR values < 2.0. However, the quartile with worst control spent 71.6% of their time out of target range compared with only 16.3% out of range in the best controlled quartile. The median period between INR tests was 16 days. Time spent outside the target range decreased as the duration of INR monitoring increased, from 52% in the first three months of monitoring to 30% after two years. A multivariate logistic regression model showed that a 10% increase in time out of range was associated with an increased risk of mortality (odds ratio (OR) 1.29, p < 0.001) and of an ischaemic stroke (OR 1.10, p = 0.006) and other thromboembolic events (OR 1.12, p < 0.001). The rate of hospitalisation was higher when INR was outside the target range.
Conclusions: Suboptimal anticoagulation was associated with poor clinical outcomes, even in a well controlled population. However, good control was difficult to achieve and maintain. New measures are needed to improve maintenance anticoagulation in patients with NVAF.


 

Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: Observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study

Background Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation (AF), but their incidence can be substantially reduced by appropriate anticoagulation. Bleeding is the major complication of anticoagulant treatment, and the relative risks for bleeding vs stroke must be considered when starting anticoagulation.

Methods The AFFIRM trial included patients with AF and at least one risk factor for stroke, randomly assigning them to either a rate-control or rhythm-control strategy. All patients were initially treated with warfarin. The incidence of protocol-defined major and minor bleeding was documented during follow-up. Variables associated with bleeding were determined using a Cox proportional hazards model, using baseline and time-dependent covariates.

Results The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years. Major bleeding occurred in 260 patients, an annual incidence of approximately 2% per year, with no significant difference between the rate-control and rhythm-control groups. Increased age, heart failure, hepatic or renal disease, diabetes, first AF episode, warfarin use, and aspirin use were significantly associated with major bleeding. Minor bleeding was common in both treatment arms, with 738 patients reporting this problem in one or more visits.

Conclusions Bleeding is a significant problem that complicates management of patients with AF. Risk factors for bleeding can be identified, and knowledge of these risk factors can be used to plan therapy.


 

Long-term survival and functional results after aortic valve replacement in asymptomatic patients with chronic severe aortic regurgitation and left ventricular dysfunction

Objectives We examined the influence of medical treatment on the results of surgery in terms of long-term survival and functional results in patients with chronic, severe aortic regurgitation (AR).
Background Asymptomatic patients with AR and a reduced left ventricular ejection fraction (LVEF) are at high risk because of a higher-than-expected long-term mortality. The influence of preoperative medical therapy on the outcome after aortic valve replacement (AVR) is not well known.
Methods Surgery was indicated for the appearance of a reduced LVEF (<50%). At the time of AVR, there were 134 patients treated with nifedipine (group A), and 132 received no medication (group B).
Results Operative mortality was similar in the two groups (0.75% vs. 0.76%, p = NS). The LVEF normalized in all of group A, whereas it remained abnormal in 36 group B patients (28%). At 10-year follow-up, LVEF persisted higher in group A (62 ± 5% vs. 48 ± 4%, p < 0.001). Five-year survival was similar in the two groups (94 ± 2% vs. 94 ± 3%, p = NS). Group A showed a 10-year survival not different from expected and significantly higher than that in group B (85 ± 4% vs. 78 ± 5%, p < 0.001), which had a worse survival than expected.
Conclusions Unloading treatment with nifedipine in AR allows one to indicate AVR at the appearance of a reduced LVEF with a low operative mortality and an optimal long-term outcome. The concept of surgical correction of AR indicated for reduced LVEF may not be applied to all patients. Indeed, in a large amount of untreated patients, a reduced LVEF preoperatively is not reversed by prompt surgery, indicating irreversible myocardial damage, and 10-year survival is worse than expected.
 

Depression as a predictor for appropriate shocks among patients with implantable cardioverter-defibrillators
Results from the Triggers of Ventricular Arrhythmias (TOVA) study

Objectives We sought to examine the relationship between symptoms of depression and shock-treated ventricular arrhythmias among implantable cardioverter-defibrillator (ICD) patients.
Background Depression predicts mortality in patients with coronary artery disease (CAD), but whether this is via an increased risk of fatal ventricular arrhythmias is unclear.
Methods We prospectively analyzed data on symptoms of depression and risk of ventricular arrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]) resulting in ICD discharge in the Triggers of Ventricular Arrhythmias (TOVA) study. Symptoms were assessed by the Center for Epidemiologic Studies-Depression (CES-D) scale. Scores of 16 to 26 and ≥27 represented mild and moderate/severe depression, respectively. The Cox and Anderson-Gill proportional hazards models were used to test for associations among all patients and patients with CAD.
Results Among 645 patients with baseline assessments, 90 (14%) were mildly depressed and 25 (3.9%) were moderately to severely depressed. Moderate/severe depression was associated with time to first shock for VT/VF (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.1 to 9.9) and all shocks for VT/VF including recurrent episodes (HR 3.2, 95% CI 1.2 to 8.6). Among the 476 CAD patients, the association with time to first shock (HR 6.4, 95% CI 1.9 to 21.1) and all shocks (HR 8.3, 95% CI 2.9 to 23.3) remained. The risk of shock for VT/VF was associated with depression severity in the total population (p for trend = 0.02) and among patients with CAD (p < 0.01), even after controlling for multiple confounders.
Conclusions More severe symptoms of depression predict shocks for VT/VF among ICD patients. The elevated risk of VT/VF among patients with CAD and depression suggests that arrhythmia may contribute significantly to total mortality in this subgroup.
 

Concerns about the implantable cardioverter defibrillator: A determinant of anxiety and depressive symptoms independent of experienced shocks

Background Patients with an implantable cardioverter defibrillator (ICD) are at increased risk of anxiety disorders. In turn, anxiety has been identified as a precipitant of ventricular arrhythmias. Anxiety may in part be attributed to concerns about the ICD firing, but the relationship between ICD concerns, psychological morbidity, and shocks has not been systematically investigated. We examined the relative importance of experienced shocks versus subjective concerns about the ICD as determinants of anxiety and depressive symptoms in ICD patients.

Methods Consecutive surviving patients (n = 182, response rate = 82%) having had an ICD implanted between October 1998 and January 2003 at the Erasmus Medical Centre Rotterdam were asked to fill in the ICD Patient Concerns Questionnaire and the Hospital Anxiety and Depression Scale. Clinical variables were obtained from the patients' medical records.

Results A total of 55 (30%) patients had received a shock from the ICD. Although patients who had experienced a shock scored higher on ICD concerns, ICD concerns was the only independent determinant of anxiety (odds ratio 6.35, 95% CI 2.84-14.20) and depressive symptoms (odds ratio 2.29, 95% CI 1.06-4.96) adjusting for shocks and all other factors.

Conclusions Patient concerns about the ICD may be an important indicator of psychosocial adjustment. Screening for ICD patient concerns using the ICD Patient Concerns Questionnaire may identify patients at risk for psychological morbidity after ICD implantation.



 

Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity

Aims Patients with diabetes have an unfavourable prognosis after an acute myocardial infarction. In the first DIGAMI study, an insulin-based glucose management improved survival. In DIGAMI 2, three treatment strategies were compared: group 1, acute insulin–glucose infusion followed by insulin-based long-term glucose control; group 2, insulin–glucose infusion followed by standard glucose control; and group 3, routine metabolic management according to local practice.
Methods and results DIGAMI 2 recruited 1253 patients (mean age 68 years; 67% males) with type 2 diabetes and suspected acute myocardial infarction randomly assigned to groups 1 (n=474), 2 (n=473), and 3 (n=306). The primary endpoint was all-cause mortality between groups 1 and 2, and a difference was hypothesized as the primary objective. The secondary objective was to compare total mortality between groups 2 and 3, whereas morbidity differences served as tertiary objectives. The median study duration was 2.1 (interquartile range 1.03–3.00) years. At randomization, HbA1c was 7.2, 7.3, and 7.3% in groups 1, 2, and 3, respectively, whereas blood glucose was 12.8, 12.5, and 12.9 mmol/L, respectively. Blood glucose was significantly reduced after 24 h in all groups, more in groups 1 and 2 (9.1 and 9.1 mmol/L) receiving insulin–glucose infusion than in group 3 (10.0 mmol/L). Long-term glucose-lowering treatment differed between groups with multidose insulin ( 3 doses/day) given to 15 and 13% of patients in groups 2 and 3, respectively compared with 42% in group 1 at hospital discharge. By the end of follow-up, HbA1c did not differ significantly among groups 1–3 ( 6.8%). The corresponding values for fasting blood glucose were 8.0, 8.3, and 8.6 mmol/L. Hence, the target fasting blood glucose for patients in group 1 of 5–7 mmol/L was never reached. The study mortality (groups 1–3 combined) was 18.4%. Mortality between groups 1 (23.4%) and 2 (22.6%; primary endpoint) did not differ significantly (HR 1.03; 95% CI 0.79–1.34; P=0.831), nor did mortality between groups 2 (22.6%) and 3 (19.3%; secondary endpoint) (HR 1.23; CI 0.89–1.69; P=0.203). There were no significant differences in morbidity expressed as non-fatal reinfarctions and strokes among the three groups.
Conclusion DIGAMI 2 did not support the fact that an acutely introduced, long-term insulin treatment improves survival in type 2 diabetic patients following myocardial infarction when compared with a conventional management at similar levels of glucose control or that insulin-based treatment lowers the number of non-fatal myocardial reinfarctions and strokes. However, an epidemiological analysis confirms that the glucose level is a strong, independent predictor of long-term mortality in this patient category, underlining that glucose control seems to be an important part of their management.
 

Cost-effectiveness of In-home Automated External Defibrillators for Individuals at Increased Risk of Sudden Cardiac Death. There's No Place Like Home?

Background/Objective: In-home automated external defibrillators (AEDs) are increasingly recommended as a means for improving survival of cardiac arrests that occur at home. The current study was conducted to explore the relationship between individuals' risk of cardiac arrest and cost-effectiveness of in-home AED deployment.
Design: Markov decision model employing a societal perspective.
Patients: Four hypothetical cohorts of American adults 60 years of age at progressively greater risk for sudden cardiac death (SCD): 1) all adults (annual probability of SCD 0.4%); 2) adults with multiple SCD risk factors (probability 2%); 3) adults with previous myocardial infarction (probability 4%); and 4) adults with ischemic cardiomyopathy unable to receive an implantable defibrillator (probability 6%).
Intervention: Strategy 1: individuals suffering an in-home cardiac arrest were treated with emergency medical services equipped with AEDs (EMS-D). Strategy 2: individuals suffering an in-home cardiac arrest received initial treatment with an in-home AED, followed by EMS.
Results: Assuming cardiac arrest survival rates of 15% with EMS-D and 30% with AEDs, the cost per quality-adjusted life-year gained (QALY) of providing in-home AEDs to all adults 60 years of age is $216,000. Costs of providing in-home AEDs to adults with multiple risk factors (2% probability of SCD), previous myocardial infarction (4% probability), and ischemic cardiomyopathy (6% probability) are $132,000, $104,000, and $88,000, respectively.
Conclusions: The cost-effectiveness of in-home AEDs is intimately linked to individuals' risk of SCD. However, providing in-home AEDs to all adults over age 60 appears relatively expensive.

Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: Results from the Canadian Registry of Atrial Fibrillation

Background After its initial diagnosis, atrial fibrillation (AF) may progress from paroxysmal to chronic AF (CAF). The rate of progression and risk factors for progression are not clearly defined.

Methods The Canadian Registry of Atrial Fibrillation (CARAF) enrolled patients from 6 Canadian cities at the time of their first electrocardiographic diagnosis of AF. Comprehensive clinical and echocardiographic data were collected and patients were followed annually, carefully documenting clinical outcomes, recurrence of paroxysmal AF, and progression to CAF. Baseline clinical, electrocardiographic, and echocardiographic variables were evaluated by univariate Cox proportionate hazards analysis. A stepwise approach was used to model the association between echocardiographic and clinical variables with progression to CAF.

Results A total of 757 patients with a baseline diagnosis of paroxysmal AF were evaluated. Median follow-up was 8.0 years (range 2 days to 11.1 years). The probability of progression to CAF by 1 year was 8.6% and thereafter there was a slow but steady progression to 24.7% by 5 years. By 5 years, the probability of documented recurrence of any AF (chronic or paroxysmal) was 63.2%. Increasing age, significant aortic stenosis or mitral regurgitation, left atrial enlargement, and diagnosis of cardiomyopathy were independently associated with progression to CAF. A more rapid heart rate during AF was associated with decreased risk of progression.

Conclusions After the initial diagnosis of paroxysmal AF, there is a slow but steady progression to CAF. Baseline echocardiographic variables, age, cardiomyopathy, and heart rate were independently associated with progression to CAF.

Day–Night Pattern of Sudden Death in Obstructive Sleep Apnea

Background The risk of sudden death from cardiac causes in the general population peaks from 6 a.m. to noon and has a nadir from midnight to 6 a.m. Obstructive sleep apnea is highly prevalent and associated with neurohormonal and electrophysiological abnormalities that may increase the risk of sudden death from cardiac causes, especially during sleep.
Methods We reviewed polysomnograms and the death certificates of 112 Minnesota residents who had undergone polysomnography and had died suddenly from cardiac causes between July 1987 and July 2003. For four intervals of the day, we compared the rates of sudden death from cardiac causes among people with obstructive sleep apnea and the following: the rates among people without obstructive sleep apnea, the rates in the general population, and the expectations according to chance. For each interval, we assessed the median apnea–hypopnea index and the relative risk of sudden death from cardiac causes. We similarly analyzed sudden death from cardiac causes during three time intervals that correlate with usual sleep–wake cycles.
Results From midnight to 6 a.m., sudden death from cardiac causes occurred in 46 percent of people with obstructive sleep apnea, as compared with 21 percent of people without obstructive sleep apnea (P=0.01), 16 percent of the general population (P<0.001), and the 25 percent expected by chance (P<0.001). People with sudden death from cardiac causes from midnight to 6 a.m. had a significantly higher apnea–hypopnea index than those with sudden death from cardiac causes during other intervals, and the apnea–hypopnea index correlated directly with the relative risk of sudden death from cardiac causes from midnight to 6 a.m. For people with obstructive sleep apnea, the relative risk of sudden death from cardiac causes from midnight to 6 a.m. was 2.57 (95 percent confidence interval, 1.87 to 3.52). The analysis of usual sleep–wake cycles showed similar results.
Conclusions People with obstructive sleep apnea have a peak in sudden death from cardiac causes during the sleeping hours, which contrasts strikingly with the nadir of sudden death from cardiac causes during this period in people without obstructive sleep apnea and in the general population.

Risk of Cardiovascular Disease by Hysterectomy Status, With and Without Oophorectomy

Background— Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in women and may vary by hysterectomy (or oophorectomy) status. This study compared CVD risk factors and rates between postmenopausal women who had and had not undergone hysterectomy, with or without oophorectomy.
Methods and Results— This analysis was conducted on 89 914 women in the Women’s Health Initiative (WHI) Observational Study. Participants reported demographic characteristics, medical history, dietary habits, physical activity, medications, and previous hysterectomy (with or without oophorectomy). Baseline weight, height, waist circumference, and blood pressure were measured. CVD events were ascertained during 5.1 years of mean follow-up and adjudicated with standard criteria. Black, Hispanic, and American Indian women had higher rates of hysterectomy than white women (52.9%, 44.6%, and 49.2% versus 40.0%, respectively), and Asian/Pacific Islander women had lower rates (33.8%). Women with a hysterectomy (regardless of oophorectomy status) had an adverse risk profile at baseline compared with women with no hysterectomy, including a higher proportion of hypertension, diabetes, high cholesterol, obesity, and lower education, income, and physical activity (all P<0.01). Total mortality and fatal and nonfatal CVD were higher among women with a hysterectomy. Hysterectomy (regardless of oophorectomy status) was a significant predictor of CVD (HR: 1.26, P<0.001). After adjustment for demographic variables and CVD risk factors, the effect was reduced and nonsignificant.
Conclusions— Women with a hysterectomy had a worse risk profile and higher prevalence and incidence of CVD in this cohort. Multivariate models suggest that hysterectomy is not the major determinant of this outcome; rather, CVD risk may be due to the more adverse initial risk profile of women who had undergone hysterectomy.


 

Quantitative Determinants of the Outcome of Asymptomatic Mitral Regurgitation

Background The clinical outcome of asymptomatic mitral regurgitation is poorly defined, and the treatment is uncertain. We studied the effect on the outcome of quantifying mitral regurgitation according to recent guidelines.
Methods We prospectively enrolled 456 patients (mean [±SD] age, 63±14 years; 63 percent men; ejection fraction, 70±8 percent) with asymptomatic organic mitral regurgitation, quantified according to current recommendations (regurgitant volume, 66±40 ml per beat; effective regurgitant orifice, 40±27 mm2).
Results The estimated five-year rates (±SE) of death from any cause, death from cardiac causes, and cardiac events (death from cardiac causes, heart failure, or new atrial fibrillation) with medical management were 22±3 percent, 14±3 percent, and 33±3 percent, respectively. Independent determinants of survival were increasing age, the presence of diabetes, and increasing effective regurgitant orifice (adjusted risk ratio per 10-mm2 increment, 1.18; 95 percent confidence interval, 1.06 to 1.30; P<0.01), the predictive power of which superseded all other qualitative and quantitative measures of regurgitation. Patients with an effective regurgitant orifice of at least 40 mm2 had a five-year survival rate that was lower than expected on the basis of U.S. Census data (58±9 percent vs. 78 percent, P=0.03). As compared with patients with a regurgitant orifice of less than 20 mm2, those with an orifice of at least 40 mm2 had an increased risk of death from any cause (adjusted risk ratio, 2.90; 95 percent confidence interval, 1.33 to 6.32; P<0.01), death from cardiac causes (adjusted risk ratio, 5.21; 95 percent confidence interval, 1.98 to 14.40; P<0.01), and cardiac events (adjusted risk ratio, 5.66; 95 percent confidence interval, 3.07 to 10.56; P<0.01). Cardiac surgery was ultimately performed in 232 patients and was independently associated with improved survival (adjusted risk ratio, 0.28; 95 percent confidence interval, 0.14 to 0.55; P<0.01).
Conclusions Quantitative grading of mitral regurgitation is a powerful predictor of the clinical outcome of asymptomatic mitral regurgitation. Patients with an effective regurgitant orifice of at least 40 mm2 should promptly be considered for cardiac surgery.

Worldwide Survey on the Methods, Efficacy, and Safety of Catheter Ablation for Human Atrial Fibrillation

Background— The purpose of this study was to conduct a worldwide survey investigating the methods, efficacy, and safety of catheter ablation (CA) of atrial fibrillation (AF).
Methods and Results— A detailed questionnaire was sent to 777 centers worldwide. Data relevant to the study purpose were collected from 181 centers, of which 100 had ongoing programs on CA of AF between 1995 and 2002. The number of patients undergoing this procedure increased from 18 in 1995 to 5050 in 2002. The median number of procedures per center was 37.5 (range, 1 to 600). Paroxysmal AF, persistent AF, and permanent AF were the indicated arrhythmias in 100.0%, 53.0%, and 20.0% of responding centers, respectively. The most commonly used techniques were right atrial compartmentalization between 1995 and 1997, ablation of the triggering focus in 1998 and 1999, and electrical disconnection of multiple pulmonary veins between 2000 and 2002. Of 8745 patients completing the CA protocol in 90 centers, of whom 2389 (27.3%) required >1 procedure, 4550 (52.0%; range among centers, 14.5% to 76.5%) became asymptomatic without drugs and another 2094 (23.9%; range among centers, 8.8% to 50.3%) became asymptomatic in the presence of formerly ineffective antiarrhythmic drugs over an 11.6±7.7-month follow-up period. At least 1 major complication was reported in 524 patients (6.0%).
Conclusions— The findings of this survey provide a picture of the variable and evolving methods, efficacy, and safety of CA for AF as practiced in a large number of centers worldwide and may serve as a guide to clinicians considering therapeutic options in patients suffering from this arrhythmia.




 

Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease

Background Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD).
Methods A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke.
Results The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality.
Conclusions Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.
 

A Randomized Trial of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease in Women

Background Randomized trials have shown that low-dose aspirin decreases the risk of a first myocardial infarction in men, with little effect on the risk of ischemic stroke. There are few similar data in women.
Methods We randomly assigned 39,876 initially healthy women 45 years of age or older to receive 100 mg of aspirin on alternate days or placebo and then monitored them for 10 years for a first major cardiovascular event (i.e., nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes).
Results During follow-up, 477 major cardiovascular events were confirmed in the aspirin group, as compared with 522 in the placebo group, for a nonsignificant reduction in risk with aspirin of 9 percent (relative risk, 0.91; 95 percent confidence interval, 0.80 to 1.03; P=0.13). With regard to individual end points, there was a 17 percent reduction in the risk of stroke in the aspirin group, as compared with the placebo group (relative risk, 0.83; 95 percent confidence interval, 0.69 to 0.99; P=0.04), owing to a 24 percent reduction in the risk of ischemic stroke (relative risk, 0.76; 95 percent confidence interval, 0.63 to 0.93; P=0.009) and a nonsignificant increase in the risk of hemorrhagic stroke (relative risk, 1.24; 95 percent confidence interval, 0.82 to 1.87; P=0.31). As compared with placebo, aspirin had no significant effect on the risk of fatal or nonfatal myocardial infarction (relative risk, 1.02; 95 percent confidence interval, 0.84 to 1.25; P=0.83) or death from cardiovascular causes (relative risk, 0.95; 95 percent confidence interval, 0.74 to 1.22; P=0.68). Gastrointestinal bleeding requiring transfusion was more frequent in the aspirin group than in the placebo group (relative risk, 1.40; 95 percent confidence interval, 1.07 to 1.83; P=0.02). Subgroup analyses showed that aspirin significantly reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction among women 65 years of age or older.
Conclusions In this large, primary-prevention trial among women, aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a nonsignificant finding with respect to the primary end point.
 

The Effect of Cardiac Resynchronization on Morbidity and Mortality in Heart Failure

Background Cardiac resynchronization reduces symptoms and improves left ventricular function in many patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. We evaluated its effects on morbidity and mortality.
Methods Patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony who were receiving standard pharmacologic therapy were randomly assigned to receive medical therapy alone or with cardiac resynchronization. The primary end point was the time to death from any cause or an unplanned hospitalization for a major cardiovascular event. The principal secondary end point was death from any cause.
Results A total of 813 patients were enrolled and followed for a mean of 29.4 months. The primary end point was reached by 159 patients in the cardiac-resynchronization group, as compared with 224 patients in the medical-therapy group (39 percent vs. 55 percent; hazard ratio, 0.63; 95 percent confidence interval, 0.51 to 0.77; P<0.001). There were 82 deaths in the cardiac-resynchronization group, as compared with 120 in the medical-therapy group (20 percent vs. 30 percent; hazard ratio 0.64; 95 percent confidence interval, 0.48 to 0.85; P<0.002). As compared with medical therapy, cardiac resynchronization reduced the interventricular mechanical delay, the end-systolic volume index, and the area of the mitral regurgitant jet; increased the left ventricular ejection fraction; and improved symptoms and the quality of life (P<0.01 for all comparisons).
Conclusions In patients with heart failure and cardiac dyssynchrony, cardiac resynchronization improves symptoms and the quality of life and reduces complications and the risk of death. These benefits are in addition to those afforded by standard pharmacologic therapy. The implantation of a cardiac-resynchronization device should routinely be considered in such patients.

 

Can Revascularization Restore Sinus Rhythm in Patients with Acute Onset Atrioventricular Block?

ABSTRACT Background: We studied patients with coronary artery disease (CAD) and complete atrioventricular (AV) block of acute onset that were treated with coronary artery bypass grafting (CABG) to see whether revascularization can restore the sinus rhythm. Methods: CABG was performed on eight patients with newly developed complete AV block and severe CAD. The distribution of coronary artery lesions showed a type IV pattern in six patients and a type II pattern in two patients. Complete revascularization was performed in six patients. Left anterior descending artery was revascularized in all eight patients. The patients were followed-up after operation for approximately 10 days before the implantation of a permanent pacemaker to see if they recover from AV block. Results: The mean interval from development of complete AV block to operation was 3.63 ± 1.3 days. There was no operative and/or early mortality. None of the patients recovered from complete AV block after coronary revascularization. Early morbidity was not detected. The mean hospital stay (12.75 ± 1.49 days) and intensive care unit stay (30.25 ± 19.39 hours) were relatively long because of the delay in permanent pacemaker implantation. All patients were asymptomatic at the end of their follow-up period (23.38 ± 18.41 months). Conclusions: Preoperatively developed complete AV block did not adversely affect the operative and early postoperative outcome of CABG operations. Recovery from complete AV block cannot be achieved by coronary revascularization performed 3.63 ± 1.3 days after the onset of complete AV block.

What resting heart rate should one aim for when treating patients with heart failure with a beta-blocker?
Experiences from the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF)

Objectives The goal of this study was to explore the question: what resting heart rate (HR) should one aim for when treating patients with heart failure with a beta-blocker?
Background The interaction of pretreatment and achieved resting HR with the risk-reducing effect of beta-blocker treatment needs further evaluation.
Methods Cardiovascular risk and risk reduction were analyzed in five subgroups defined by quintiles (Q) of pretreatment resting HR in the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF).
Results Mean baseline HR in the 5 Qs were 71, 76, 81, 87, and 98 beats/min; achieved HR 63, 66, 68, 72, and 75 beats/min; and net change −8, −10, −11, −13, and −14 beats/min, respectively. Baseline HR was related to a number of baseline characteristics. Cardiovascular risk was no different in Q1 toQ 4 (placebo groups) but increased in Q5 (HR above 90 beats/min). No relationship was observed between the risk-reducing effect of metoprolol controlled release/extended release (CR/XL) and baseline HR in the five Qs of baseline HR, or achieved HR, or change in HR during follow-up, respectively.
Conclusions Metoprolol CR/XL significantly reduced mortality and hospitalizations independent of resting baseline HR, achieved HR, and change in HR. Achieved HR and change in HR during follow-up were closely related to baseline HR; therefore, it was not possible to answer the question posed. Instead, one has to apply a very simple rule: aim for the target beta-blocker dose used in clinical trials, and strive for the highest tolerated dose in all patients with heart failure, regardless of baseline and achieved HR.
 

Correlation of atrial electrocardiographic amplitude with radiofrequency energy required to ablate cavotricuspid isthmus-dependent atrial flutter

Objectives The purpose of this study was to evaluate a possible correlation between atrial ECG amplitude in common atrial flutter (AFL) and radiofrequency (RF) energy required to achieve cavotricuspid isthmus block.
Background The amount of RF delivery required for ablation of typical AFL is variable. This variation has been attributed to the cavotricuspid isthmus anatomy. Atrial ECG amplitude can be a marker of atrial anatomic variations and therefore may correlate with RF duration required to achieve cavotricuspid isthmus block.
Methods Seventy consecutive patients were prospectively studied. Ablation of the cavotricuspid isthmus was performed by creating a line of block between the inferior tricuspid annulus and the inferior caval vein using 8-mm-tip electrode catheters. If more than 20 minutes of RF time was required to achieve conduction block, the catheter was changed to an irrigated-tip catheter. Atrial ECG amplitude was assessed in leads II, III, aVF, and aVL.
Results A total of 14 ± 11 minutes of RF energy was delivered to achieve block in all patients; 12 patients (8%) required more than 20 minutes. Atrial ECG amplitude showed highly significant correlations with cumulative RF energy (F and P waves in lead II: r = 0.703 and r = 0.737, P < .001). P-wave amplitude <0.2 mV and/or flutter wave amplitude <0.35 mV in lead II have a high negative predictive value to predict <20 min RF delivery (96% and 89% respectively).
Conclusions A significant correlation exists between atrial ECG amplitude and amount of RF required to ablate typical AFL. Atrial ECG amplitude may be a surrogate marker of characteristics of isthmus anatomy. These findings may influence the choice of catheter used for cavotricuspid isthmus ablation.
 

Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome

Objectives The purpose of this study was to compare the effect of intravenous flecainide and ajmaline with respect to their ability to induce or accentuate the typical ECG pattern of Brugada syndrome.
Background Brugada syndrome is associated with a high incidence of sudden cardiac death. The typical ECG pattern of ST-segment elevation in the right precordial leads often is concealed, but it can be unmasked with sodium channel blockers such as flecainide and ajmaline. Little is known about the relative effectiveness of these provocative agents in unmasking Brugada syndrome.
Methods Intravenous pharmacologic challenge with flecainide and ajmaline was performed. Whole-cell patch clamp techniques were used to assess the relative potency of ajmaline and flecainide to inhibit the transient outward current (Ito).
Results A coved-type ST-segment elevation in the right precordial leads was induced or enhanced in 22 of 22 patients following ajmaline administration. Among the 22 patients, only 15 patients showed positive response to flecainide, resulting in a positive concordance of 68%. Both drugs produced equivalent changes in QRS and PQ intervals, suggesting similar effects on sodium channel current. Whole-cell patch clamp experiments revealed a reduction of the total charge provided by Ito with an IC50 of 216 and 15.2 μM for ajmaline and flecainide, respectively.
Conclusions Our data demonstrate disparate response of Brugada patients to flecainide and ajmaline, with a failure of flecainide in 7 of 22 cases (32%). Greater inhibition of Ito by flecainide may render it less effective. These observations have important implication for identification of patients at risk for sudden death.
 

Genetic susceptibility to acquired long QT syndrome: Pharmacologic challenge in first-degree relatives

Objectives The purpose of this study was to test for a genetic component to risk for acquired long QT syndrome (LQTS).
Background Many drugs prolong the QT interval, and some patients develop excessive QT prolongation and occasionally torsades de pointes—the acquired LQTS. Similarities between the acquired and congenital forms of the long QT syndrome suggest genetic factors modulate susceptibility.
Methods Intravenous quinidine was administered to 14 relatives of patients who safely tolerated chronic therapy with a QT-prolonging drug (control relatives) and 12 relatives of patients who developed acquired LQTS, and ECG intervals between groups were compared.
Results Baseline QT and heart-rate corrected QT (QTc) were similar (QT/QTc: 394 ± 28/410 ± 20 ms vs 395 ± 24/418 ± 20 ms; control vs acquired LQTS) and prolonged equally in the two groups. The interval from the peak to the end of the T wave, an index of transmural dispersion of repolarization, prolonged significantly with quinidine in acquired LQTS relatives (63 ± 17 to 83 ± 18 ms, P = .017) but not in control relatives (66 ± 19 to 71 ± 18 ms, P = 0.648). In addition, the baseline peak to end of the T wave as a fraction of the QT interval was similar in both groups but was longer in acquired LQTS relatives after quinidine (16.3 ± 3.5% and 19.5 ± 3.9% in control and acquired LQTS relatives, respectively, P = .042).
Conclusions First-degree relatives of patients with acquired long QT syndrome have greater drug-induced prolongation of terminal repolarization compared to control relatives, supporting a genetic predisposition to acquired long QT syndrome.
 

Antiarrhythmic effect of carvedilol after acute myocardial infarction. Results of the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) trial

Objectives Whether beta-blockers reduce atrial arrhythmias and, when added to an angiotensin-converting enzyme (ACE) inhibitor, ventricular arrhythmia is unknown.
Background Ventricular and atrial arrhythmias are common after acute myocardial infarction (AMI) and are associated with a poor prognosis. Angiotensin-converting enzyme inhibitors reduce the incidence of both types of arrhythmia.
Methods The antiarrhythmic effect of carvedilol was examined in a placebo-controlled multicenter trial, the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) study, which enrolled 1,959 patients with reduced left ventricular systolic function after AMI, 98% of whom were treated with an ACE inhibitor.
Results The incidence of atrial fibrillation/flutter was 53 to 984 (5.4%) in the placebo group and 22 to 975 (2.3%) in the carvedilol group, giving a carvedilol/placebo hazard ratio (HR) of 0.41 (95% confidence interval [CI] 0.25 to 0.68; p = 0.0003). The corresponding rates of ventricular tachycardia/flutter/fibrillation were 38 to 984 (3.9%) and 9 to 975 (0.9%) (HR 0.24, 95% CI 0.11 to 0.49; p < 0.0001).
Conclusions Carvedilol has a powerful antiarrhythmic effect after AMI, even in patients already treated with an ACE inhibitor. Carvedilol suppresses atrial as well as ventricular arrhythmias in these patients.
 

Association of interatrial shunts and migraine headaches. Impact of transcatheter closure

Objectives To examine the relationship between patent foramen ovale (PFO) or atrial septal defect (ASD) with the incidence of migraine headache (MHA) and assess whether closure of the interatrial shunt in patients with MHA would result in improvement of MHA.
Background Migraine headache is present in 12% of adults and has been associated with interatrial communications. This study examined the relationship between PFO or ASD with the incidence of MHA and assessed whether closure of the interatrial shunt in patients with MHA would result in improvement of MHA.
Methods A sample of 89 (66 PFO/23 ASD) adult patients underwent transcatheter closure of an interatrial communication using the CardioSEAL (n = 22), Amplatzer PFO (n = 43), or the Amplatzer ASD (n = 24) device.
Results Before the procedure, MHA was present in 42% of patients (45% of patients with PFO and 30% of patients with ASD). At three months after the procedure, MHA disappeared completely in 75% of patients with MHA and aura and in 31% of patients with MHA without aura. Of the remaining patients, 40% had significant improvement (≥2 grades by the Migraine Disability Assessment Questionnaire) of MHA.
Conclusions Transcatheter closure of PFO or ASD results in complete resolution of MHA in 60% of patients (75% of patients with migraine and aura) and improvement in symptoms in 40% of the remaining patients. Interatrial communications may play a role in the etiology of MHA either through paradoxic embolism or humoral factors that escape degradation in bypassing the pulmonary circulation. A randomized trial is needed to determine whether transcatheter closure of interatrial shunts is an effective treatment for MHA.
 

Cost-effectiveness of physiologic pacing: Results of the Canadian Health Economic Assessment of Physiologic Pacing

Objectives The purpose of this study was to determine the cost-effectiveness of physiologic pacemakers.
Background The Canadian Trial of Physiologic Pacing (CTOPP) was a large randomized trial that evaluated the efficacy of physiologic pacing compared with ventricular pacing. CTOPP also included a prospective cost-effectiveness substudy.
Methods Resource usage and costs were collected from a subset of 472 patients (of 1,094) who received a physiologic pacemaker and 586 (of 1,474) who received a ventricular pacemaker. Costs included initial pacemaker implantation and all health care follow-up costs over a follow-up of 5.2 years. Costs are reported in 2004 Canadian dollars (C$1 = US$0.76), with adjustments for censoring. Incremental cost-effectiveness was estimated as the ratio of the difference (treatment-control) in mean cost to the difference in life expectancy (mean survival), with costs and effects discounted at 3% per year.
Results Over a mean follow-up of 3.1 years, physiologic pacing was associated with a gain of 0.01 life-years. This benefit increases to 0.25 life-years in the subgroup of patients with an intrinsic (unpaced) heart rate ≤60 bpm. Physiologic pacing was more expensive than ventricular (C$16,833 vs $13,857), largely because of the increased cost of dual-chamber devices. Among all substudy patients, the incremental cost-effectiveness of physiologic pacing is C$297,600 per life-year gained; however, this value falls to C$16,343 in patients with an intrinsic heart rate >60.
Conclusions In the short term, a strategy of routine implantation of physiologic pacemakers is not cost-effective by currently accepted standards. The selective use of these devices in patients likely to be pacemaker dependent appears to be cost-effective. Further studies with longer follow-up and which consider the benefit of reducing nonfatal cardiac events would be valuable.

 

Relationship between atrial tachyarrhythmias and symptoms

Objectives The purpose of this study was to correlate patient-reported symptoms of atrial fibrillation with the underlying rhythm.
Background The reliability of patient-reported symptoms as a marker of atrial fibrillation recurrence has not been well studied.
Methods This prospective multicenter trial correlated the recurrence of atrial tachyarrhythmias with symptoms in patients with a history of atrial fibrillation and a standard indication for permanent pacing. Pacemaker-detected atrial tachyarrhythmia events were correlated with symptoms. Patients logged symptomatic events into the device’s memory via an external manual activator. Patients were followed for 12 months and were contacted weekly to ensure compliance with activator usage. Episodes were classified as symptomatic atrial tachyarrhythmia, asymptomatic atrial tachyarrhythmia, or symptomatic nonatrial tachyarrhythmia depending on concordance between patient symptoms and the rhythm.
Results Forty-eight patients underwent implantation of a DDDRP pacemaker and were followed for 12 ± 2 months. A median of 25.0 (4.0–55.8) symptomatic events attributed to atrial fibrillation. A median of 1.0 (0.0–10.0) symptomatic atrial tachyarrhythmia episodes were documented during follow-up. Symptoms related to atrial fibrillation were reported in 6% of atrial tachyarrhythmia episodes identified by the pacemaker. The probability that symptoms were associated with an atrial tachyarrhythmia (positive predictive value) was 17%. The ventricular rate between symptomatic and asymptomatic atrial tachyarrhythmia events was not significantly different.
Conclusions Among patients with symptomatic bradycardia and a history of atrial fibrillation, symptoms of atrial fibrillation often were not associated with documented atrial tachyarrhythmias, and more than 90% of atrial tachyarrhythmias were clinically silent.
 

Effectiveness of fludrocortisone and salt in preventing syncope recurrence in children. A double-blind, placebo-controlled, randomized trial

Objectives We sought to evaluate the effectiveness of salt and fludrocortisone versus placebo in the prevention of syncope recurrence in children.
Background Intravascular volume expansion with fludrocortisone and salt has been reported to be effective in the treatment of syncope in children. However, no pediatric placebo-controlled data are available on the effectiveness of this mode of therapy.
Methods Thirty-three children with syncope or severe presyncope were randomized in a double-blinded fashion to receive either fludrocortisone 0.1 mg/day and salt 1 g/day or placebo two capsules per day for one year. All children had a positive tilt test before enrollment.
Results Thirty-two children (20 female) had follow-up. Their age was (mean ± SD) 13.9 ± 2.5 years. The number of syncopal episodes before therapy was 4.4 ± 4.8. Therapy was continued for 176 ± 117 days, and follow-up including time after discontinuation of medications was 1.2 ± 0.8 years. The demographics were similar in the 18 children treated with fludrocortisone and salt compared with the 14 children on placebo. Data for up to one year of randomization were included in analyses. Symptoms recurred in 10 of 18 children on fludrocortisone and salt and in 5 of 14 children on placebo (p < 0.04). Children on placebo had no symptoms until they discontinued their study medications.
Conclusions These data, coupled with the reported comparable effect of many medications used in the treatment of syncope, raise the potential of a significant placebo effect with pharmacologic therapy.
 

The Impact of Supraventricular Tachycardias on Driving Ability in Patients Referred for Radiofrequency Catheter Ablation

Aim: The aim of the present study was to evaluate the occurrence of arrhythmia-related symptoms in patients with supraventricular tachycardia (SVT) referred for radiofrequency catheter ablation (RF ablation) with special focus on driving ability.
Methods and Results: Of the 301 patients referred for RF ablation between November 1998 and December 2000 due to SVT 226 were active drivers. The present study is an interview study with structured questions. Hemodynamic symptoms were frequently encountered during tachycardia. The symptoms occurred irrespective of driving. In the 226 active drivers, fatigue was reported in 77%, dizziness in 47%, breaking into a cold sweat in 52%, near-syncope in 50%, and syncope in 14%. Women experienced all symptoms more frequently than men: fatigue (P < 0.05), dizziness (P < 0.01), cold sweat (P < 0.05), near-syncope (P < 0.001), and syncope (P < 0.01). Fifty-seven percent of the patients had experienced tachycardia while driving, and 42% of those patients had to stop because of it. Twenty-four of all patients considered their tachycardia as an obstacle to driving. There was a significant correlation (P < 0.001) between having experienced near-syncope and considering the risk for tachycardia as an obstacle.
Conclusions: SVT frequently occurs during driving and is often associated with hemodynamic symptoms including near-syncope and syncope. Women reported tachycardia-related hemodynamic symptoms more often than men. There is a correlation between having experienced near-syncope and considering tachycardia as an obstacle to driving. The risk for serious tachycardia-related symptoms should be considered, especially in occupational drivers.

Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation The Losartan Intervention For End point reduction in hypertension (LIFE) study

Objectives We assessed the impact of antihypertensive treatment in hypertensive patients with electrocardiographic (ECG) left ventricular (LV) hypertrophy and a history of atrial fibrillation (AF).
Background Optimal treatment of hypertensive patients with AF to reduce the risk of cardiovascular morbidity and mortality remains unclear.
Methods As part of the Losartan Intervention For End point reduction in hypertension (LIFE) study, 342 hypertensive patients with AF and LV hypertrophy were assigned to losartan- or atenolol-based therapy for 1,471 patient-years of follow-up.
Results The primary composite end point (cardiovascular mortality, stroke, and myocardial infarction) occurred in 36 patients in the losartan group versus 67 in the atenolol group (hazard ratio [HR] = 0.58, 95% confidence interval [CI] 0.39 to 0.88, p = 0.009). Cardiovascular deaths occurred in 20 versus 38 patients in the losartan and atenolol groups, respectively (HR = 0.58, 95% CI 0.33 to 0.99, p = 0.048). Stroke occurred in 18 versus 38 patients (HR = 0.55, 95% CI 0.31 to 0.97, p = 0.039), and myocardial infarction in 11 versus 8 patients (p = NS). Losartan-based treatment led to trends toward lower all-cause mortality (30 vs. 49, HR = 0.67, 95% CI 0.42 to 1.06, p = 0.090) and fewer pacemaker implantations (5 vs. 15, p = 0.065), whereas hospitalization for heart failure took place in 15 versus 26 patients and sudden cardiac death in 9 versus 17, respectively (both p = NS). The benefit of losartan was greater in patients with AF than those with sinus rhythm for the primary composite end point (p = 0.019) and cardiovascular mortality (p = 0.039).
Conclusions Losartan is more effective than atenolol-based therapy in reducing the risk of the primary composite end point of cardiovascular morbidity and mortality as well as stroke and cardiovascular death in hypertensive patients with ECG LV hypertrophy and AF.
 

Pharmacologic Strategies for Prevention of Atrial Fibrillation After Open Heart Surgery

Postoperative atrial fibrillation is a common complication after open heart surgery; it increases morbidity, hospital stay, and costs. In an analysis of 8 large cardiac surgery trials totaling 20,193 patients, the incidence of postoperative atrial fibrillation was estimated to be 26% and ranged from 17% to 35%. We reviewed the results of 52 studies published between 1966 and 2003 that evaluated pharmacologic strategies to prevent postoperative atrial fibrillation in nearly 10,000 patients undergoing open heart operations. Supraventricular tachyarrhythmias, including atrial fibrillation, after open heart operations occurred in 29% of patients who did not receive prophylactic drugs, compared with 12% in patients who received intravenous followed by oral amiodarone, 15% in those given sotalol, 16% in those given oral amiodarone, and 19% in those given ß-blockers. Pharmacologic strategies and regimens aimed at preventing postoperative atrial fibrillation are necessary to optimize the postoperative care of patients undergoing open heart operations. Although no strategy has consistently been shown to be superior to another, the most effective approach to preventing postoperative atrial fibrillation likely involves multiple interventions. In the absence of contraindications, all patients should receive ß-blocker therapy before and after the operation. For patients with 1 or more risk factors for postoperative atrial fibrillation, regimens consisting of either sotalol (ß-blocker with class III antiarrhythmic properties) alone or ß-blockers in combination with amiodarone seem to be the safest, most effective pharmacologic strategies for preventing postoperative atrial fibrillation.
 

Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy

Objectives The goal of this study was to assemble a profile and assess the significance of arrhythmias in a nontertiary-based hypertrophic cardiomyopathy (HCM) cohort.
Background Hypertrophic cardiomyopathy is associated with arrhythmia-related consequences, particularly sudden death. Ventricular tachyarrhythmias on Holter electrocardiograms (ECG) have been reported as markers for sudden death in highly selected HCM populations.
Methods We assessed the profile of ventricular and supraventricular ectopy and bradyarrhythmia on ambulatory 24-h Holter ECG and also related these findings to clinical outcome in 178 HCM patients.
Results Of the 178 study patients, 157 (88%) had premature ventricular complexes (PVCs), including 21 (12%) with ≥500 PVCs, 74 (42%) had couplets, 67 (37%) had supraventricular tachycardia (SVT), and 56 (31%) had nonsustained ventricular tachycardia (NSVT). Mean number of PVCs was 330 ± 763 (range 1 to 5,435) and increased with age (p < 0.01); NSVT was associated with greater left ventricular hypertrophy (p = 0.01) and severe symptoms (New York Heart Association functional classes III and IV) (p = 0.04); SVT occurred more commonly in patients with outflow obstruction (p = 0.02). Over a follow-up of 5.5 ± 3.4 years, 11 (6%) patients died suddenly (annual mortality rate, 1.1%) including 5 patients with NSVT. For sudden death, NSVT on Holter ECG had negative and positive predictive values of 95% and 9%, and sensitivity and specificity of 45% and 69%, respectively.
Conclusions In this nontertiary-based HCM cohort, ventricular and supraventricular tachyarrhythmias were particularly frequent and demonstrated a broad spectrum on ambulatory (Holter) ECG. Paradoxically, despite such a highly arrhythmogenic substrate, sudden death events proved to be relatively uncommon. Ventricular tachyarrhythmias had a low positive and relatively high negative predictive value for sudden death in this HCM population.
 

Indications for and Long-Term Survival in Patients With Automatic Implantable Cardioverter-Defibrillators

Automatic implantable cardioverter-defibrillators (AICDs) were implanted in 378 men and 95 women, mean age 69 +/- 12 years. At 3.6-year follow up, survival was 76% in patients who had an AICD because of cardiac arrest as a result of ventricular fibrillation or ventricular tachycardia not resulting from a transient or reversible cause; 85% in patients who had an AICD because of spontaneous sustained ventricular tachycardia in association with structural heart disease; 92% in patients who had an AICD because of syncope of undetermined origin with clinically relevant, hemodynamically sustained ventricular tachycardia or ventricular fibrillation induced at electrophysiological study when drug therapy is ineffective, not tolerated, or not preferred; 84% in patients who had an AICD because of nonsustained ventricular tachycardia with coronary artery disease, prior myocardial infarction, left ventricular dysfunction, and inducible ventricular fibrillation or sustained ventricular tachycardia at electrophysiological study that is not suppressible by a class I antiarrhythmic drug; and 85% in all 473 patients who had an AICD.

Migraine headache relief after transcatheter closure of patent foramen ovale

Objectives The purpose of this study was to determine the effects of transcatheter patent foramen ovale (PFO) closure on migraine frequency in patients with paradoxical cerebral embolism.
Background The prevalence of migraine headache is higher in cryptogenic stroke patients with PFO than in the general population. Previous studies have suggested that closure of the PFO may reduce migrainous symptoms.
Methods Between April 2001 and December 2003, 162 consecutive patients with paradoxical cerebral embolism underwent transcatheter PFO closure for prevention of recurrent cryptogenic stroke or transient ischemic attack. A one-year retrospective analysis of migraine symptoms before and after PFO closure was performed.
Results Active migraine was present in 35% (57 of 162) of patients, and 68% (39 of 57) experienced migrainous aura; 50 patients were available for analysis at one year. Complete resolution of migraine symptoms occurred in 56% (28 of 50) of patients, and 14% (7 of 50) of patients reported a significant (≥50%) reduction in migraine frequency. Patients reported an 80% reduction in the mean number of migraine episodes per month after PFO closure (6.8 ± 9.6 before closure vs. 1.4 ± 3.4 after closure, p < 0.001). Results were independent of completeness of PFO closure at one year.
Conclusions In patients with paradoxical cerebral embolism, migraine headaches are more frequent than in the general population, and transcatheter closure of the PFO results in complete resolution or marked reduction in frequency of migraine headache.
 

Heart failure hospitalization is more common in pacemaker patients with sinus node dysfunction and a prolonged paced QRS duration

Objectives The purpose of this study was to determine whether a prolonged paced QRS duration increases the risk of cardiac dysfunction.
Background Right ventricular apical pacing mimics left bundle branch block, results in a prolonged QRS duration of variable duration, and causes ventricular desynchronization.
Methods In the Mode Selection Trial (MOST), QRS duration was measured in patients who had at least one paced ventricular complex recorded on 12-lead ECG within 3 months of enrollment (early) and after 9 months (late). Clinical endpoints including heart failure hospitalization, mortality, and atrial fibrillation were analyzed. A total of 1,026 patients were included in the analysis. Median age was 75 years (25th, 75th percentiles = 69, 80) and median ejection fraction prior to implant was 55% (45, 60). The cumulative percent ventricular pacing (DDDR and VVIR) was 81% over a median follow-up of 33 months. During period, 123 patients had heart failure hospitalization, 197 died, and 261 patients had atrial fibrillation.
Results Cox proportional hazards models demonstrated that paced QRS duration was a strong predictor of heart failure hospitalization (hazard ratio 1.15; 95% confidence interval 1.07,1.23) for each 10-ms increase in paced QRS duration (P = .001). The increased risk was unaffected by adjustment for other known predictors of heart failure hospitalization in the study. Paced QRS duration was not significant for mortality (P = .41) or atrial fibrillation (P = .20) when baseline QRS duration and other predictors were included.
Conclusions Paced QRS duration is a significant, independent predictor of heart failure hospitalization in patients with sinus node dysfunction. A very long paced QRS duration is associated with increased heart failure hospitalization.
 

One conversion of ventricular fibrillation is adequate for implantable cardioverter-defibrillator implant: An analysis from the Low Energy Safety Study (LESS)

Objectives The purpose of this study was to analyze defibrillation conversion data from the Low Energy Safety Study (LESS) to determine how implant criteria that use fewer inductions of ventricular fibrillation (VF) correlate with outcome and, in particular, to assess the reliability of using a single VF induction and test shock at 14 J.
Background A safety margin of 10 J has become standard for implantation of an implantable cardioverter-defibrillator (ICD), but the specifics and rigor of the implant test sequence are not standardized.
Methods In LESS, 611 ICD recipients completed a rigorous VF induction test scheme that began at 14 J and continued until the energy that succeeded three times without a failure was determined (DFT++). The data were analyzed to determine how well the outcome of the first 14-J shock and various other combinations of first and/or second shocks predicted a rigorous gold standard of DFT++ ≤21 J (i.e., three successes at ≤21 J).
Results The positive predictive accuracy for the 91% of patients in whom the first 14-J shock succeeded was virtually identical to the positive predictive accuracy for the commonly used criteria of two successes at ≤17 J (99.1% vs 99.0%, P = .69), and slightly higher than the positive predictive accuracy for two successes at ≤21 J (98.8%, P = .51). A single success at 17 J or 21 J had a somewhat lower positive predictive accuracy of 98.2% (P = .17). Eliminating VF induction testing would have resulted in a significantly lower positive predictive accuracy of 97.1% (P = .01).
Conclusions A single conversion success at 14 J on the first VF induction provides similar positive predictive accuracy as two successes at 17 J or 21 J. Using this criterion, 91% of patients meet implant criteria with a single induction of ventricular fibrillation.
 

Topographic Variability of the Esophageal Left Atrial Relation Influencing Ablation Lines in Patients with Atrial Fibrillation

Introduction: The close anatomic relationship of the posterior wall of the left atrium (LA) and the thermosensitive esophagus creates a potential hazard in catheter ablation procedures.
Methods and Results: In 30 patients (pts) with atrial fibrillation (AF) undergoing catheter ablation, we prospectively studied the course and contact of the esophagus in relation to LA and the topographic proximity to ablation lines encircling the right-sided and left-sided pulmonary veins (PV) as well as to the posterior line connecting the encircling lines using the electromagnetic mapping system for reconstruction of LA and for tagging of the esophagus. This new technique of anatomic tagging of the esophagus was validated against the CT scan as a standard imaging procedure. The esophageal course was highly variable, extending from courses in direct vicinity to the left- or right-sided PV as well as in the midportion of the posterior LA. In order to avoid energy application in direct proximity to the esophagus, adjustments of the left and right PV encircling lines were necessary in 14/30 pts (47%) and 3/30 (10%). In 30 pts (100%), the mid- to inferior areas of the posterior LA revealed contact with the esophagus. Therefore, posterior and inferior linear ablation lines were abandoned and shifted to superior in 29 pts (97%).
Conclusions: Anatomic tagging of esophagus revealed a highly variable proximity to different areas of the posterior LA suggesting individual adjustment of encircling and linear ablation lines in AF ablation procedures to avoid the life threatening complication of esophagus perforation.
 

Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death

Aims Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice.
Methods and results All 284 426 case reports of suspected adverse drug reactions of drugs with known anti-HERG activity received by the International Drug Monitoring Program of the World Health Organization (WHO-UMC) up to the first quarter of 2003, were used to calculate reporting odds ratios (RORs). Cases were defined as reports of cardiac arrest, sudden death, torsade de pointes, ventricular fibrillation, and ventricular tachycardia (n=5591), and compared with non-cases regarding the anti-HERG activity, defined as the effective therapeutic plasma concentration (ETCPunbound) divided by the HERG IC50 value, of suspected drugs. We identified a significant association of 1.93 (95% CI: 1.89–1.98) between the anti-HERG activity of drugs, measured as log10 (ETCPunbound/IC50), and reporting of serious ventricular arrhythmias and sudden death to the WHO-UMC database.
Conclusion Anti-HERG activity is associated with the risk of reports of serious ventricular arrhythmias and sudden death in the WHO-UMC database. These findings are in support of the value of pre-clinical HERG testing to predict pro-arrhythmic effects of medicines.

 

Highly accurate coronary angiography with submillimetre, 16 slice computed tomography

Objective: To assess submillimetre coronary computed tomographic angiography (CTA) in comparison with invasive quantitative coronary angiography as the gold standard and to examine the effect of significant coronary artery calcification (CAC), which is known to impede lumen visualisation, on the accuracy of the examination.
Methods: After invasive coronary angiography, 58 patients underwent coronary imaging with a GE Lightspeed 16 computed tomography (CT) system. CAC was quantified after an ECG triggered acquisition with a low tube current. Coronary CTA was performed with retrospective ECG gating and a 16 x 0.63 mm collimation and was reconstructed with an effective 65–250 ms temporal resolution. All 13 major coronary artery segments were evaluated for the presence of 50% stenosis, and compared with the gold standard.
Results: One patient moved and could not be evaluated. All segments (except occluded segments) were evaluated for 57 patients. Overall the accuracy of coronary CTA for detection of 50% stenosis was: sensitivity 83%, specificity 97%, positive predictive value 80%, and negative predictive value 97%. The number of diseased coronary arteries was correctly diagnosed in 34 of 38 (89%) patients overall. Altogether 21 of 57 (37%) patients had a CAC score 400, which was predefined as representing significant CAC. Excluding these patients from the analysis improved the accuracy of coronary CTA to a sensitivity of 89%, specificity 98%, positive predictive value 79%, and negative predictive value 99%.
Conclusions: Non-invasive coronary angiography with submillimetre CT is reliable and accurate. It appears that a subgroup of patients may be selected based on CAC score in whom the investigation has even higher accuracy. Coronary CTA has reached the stage where it should be considered for a clinical role. Further research is required to define this role.
 

QTc Prolongation by Grapefruit Juice and Its Potential Pharmacological Basis, HERG Channel Blockade by Flavonoids

Background— A high intake of dietary flavonoids, which are abundant in fruits, vegetables, tea, and wine, is known to reduce cardiovascular mortality. The effects of flavonoids on cardiac electrophysiology, which theoretically may have both antiarrhythmic and proarrhythmic consequences, have not been studied systematically to date.
Methods and Results— We screened a broad spectrum of flavonoids for their inhibitory activity on HERG channels by using heterologous expression in Xenopus oocytes. At a concentration of 1 mmol/L, 10 compounds caused a significant inhibition of HERG currents, whereas 11 other flavonoids had no effect. The IC50 value for HERG block by naringenin, the most potent inhibitor, was 102.3 µmol/L in Xenopus oocytes and 36.5 µmol/L in HEK cells. To demonstrate the physiological relevance of these findings, we studied the effects of pink grapefruit juice, which contains large amounts of naringenin glycosides (>1000 µmol/L), in human volunteers. In 10 persons, we observed a peak QTc prolongation of 12.5±4.2 ms 5 hours after oral ingestion of 1 L of grapefruit juice. This effect was significant (P=0.02).
Conclusions— We found a significant QTc prolongation by grapefruit juice in healthy volunteers, probably caused by block of HERG channels by flavonoids. These findings reveal new perspectives on the potential for dietary modification of cardiac electrophysiology.
 

Exposure to traffic and the onset of myocardial infarction

Study Question: Does exposure to traffic trigger acute myocardial infarction (MI)?
Methods: Data from the Cooperative Health Research in the Region of Augsburg Myocardial Infarction Registry in southern Germany were used to conduct a case-crossover study in which incidences of MI were identified for the period February 1999 to July 2001. There were 691 subjects for whom the date and time of MI were known, who had survived for at least 24 h after the event, who had completed the registry’s standardized interview, and who had provided information on factors that may have triggered the MI.
Results: An association was found between exposure to traffic and the onset of an MI within the next 1 h (odds ratio 2.92; 95% CI, 2.22–3.83; p<0.001). The time that subjects spent in cars, on public transportation, or on motorcycles or bicycles was consistently linked with an increase in the risk of MI. Use of a car was the most common source of exposure to traffic; nevertheless, there was also an association between time spent on public transportation and the onset of an MI.
Conclusions: Transient exposure to traffic may increase the risk of MI in susceptible persons.
Perspective: The present study suggests that exposure to traffic (presumably mediated by either inhaled pollutants or mental stress) can trigger acute MI. It is unrealistic to counsel patients to avoid stress, autos, and pollution. Perhaps such data can be used to counsel our politicians to find effective and lasting solutions to overcrowding and our current hydrocarbon-based society. DB
N Engl J Med 2004;351:1721–30.
 

The impact of implantable cardioverter-defibrillator therapy on survival in autosomal-dominant arrhythmogenic right ventricular cardiomyopathy (ARVD5)

Objectives We sought to determine the impact of implantable cardioverter-defibrillator (ICD) therapy in patients with familial arrhythmogenic right ventricular cardiomyopathy (ARVC).
Background Arrhythmogenic right ventricular cardiomyopathy is a cause of sudden cardiac death, which may be prevented by ICD.
Methods We studied 11 families in which a 3p25 deoxyribonucleic acid (DNA) haplotype at locus ARVD5 segregated with disease and compared mortality in subjects who received an ICD with that in control subjects who were matched for age, gender, ARVC status, and family. Subjects (n = 367) at 50% a priori risk of inheriting ARVC were classified as high risk (HR) (n = 197), low risk (n = 92), or unknown (n = 78) on the basis of clinical events, DNA haplotyping, and/or pedigree position. Forty-eight HR subjects (30 males, [median age 32 years] and 18 females [median age 41 years]) were followed after ICD (secondary to ventricular tachycardia [VT] in 27%). Survival was compared with 58 HR control subjects who were alive at the same age to-the-day at which the ICD subject received the device.
Results In the HR group, 50% of males were dead by 39 years and females by 71 years: relative risk of death was 5.1 (95% confidence interval 3 to 8.5) for males. The five-year mortality rate after ICD in males was zero compared with 28% in control subjects (p = 0.009). Within five years, the ICD fired for VT in 70% and for VT >240 beats/min in 30%, with no difference in discharge rate when analyzed by ICD indication.
Conclusions The unknown mutation at the ARVD5 locus causing ARVC results in high mortality. Risk stratification using genetic haplotyping and ICD therapy produced improved survival for males.

Coronary syndromes following aspirin withdrawal. A special risk for late stent thrombosis

Objectives We sought to determine whether aspirin withdrawal is an encountered situation in coronary disease patients who relapsed.
Background Despite the recognized benefits of aspirin in coronary disease, and because of the threat of bleeding or poor compliance, aspirin intake is sometimes stopped. It is not known whether withdrawal of aspirin can be harmful in coronary-disease patients.
Methods Between September 1999 and April 2002, a total of 1,236 patients hospitalized for acute coronary syndrome (ACS) were questioned in order to determine whether aspirin intake had been interrupted.
Results Fifty-one of these ACSs occurred within 1 month after aspirin withdrawal. This represents 4.1% of all coronary events but 13.3% of recurrences. Among those patients who relapsed, the incidence of ST-segment elevation ACS was higher in those who stopped aspirin when compared to the 332 patients who did not stop aspirin (39% vs. 18%; p = 0.001). Ten (20%) cases involved a thrombosis of an uncoated stent implanted on average 15.5 ± 6.5 months previously. Mean delay between aspirin withdrawal and the acute coronary event was 10 ± 1.9 days. Reasons for aspirin withdrawal included minor surgery in 7 cases, fibroscopy in 8 cases, dental treatment in 13 cases, bleeding in 3 cases, and patient non-compliance in 20 cases.
Conclusions Our results support the hypothesis that aspirin withdrawal in coronary patients may represent a real risk for the occurrence of a new coronary event. Many cases involved late uncoated-stent thrombosis. Assessment of the exact incidence of coronary recurrences after aspirin withdrawal will need prospective studies.
 

Cardiac medical therapy in patients after undergoing coronary artery bypass graft surgery A review of randomized controlled trials

The purpose of this paper is to review the randomized controlled trial (RCT) data investigating cardiac medical therapy for patients after coronary artery bypass grafting (CABG). We identified RCTs with ≥100 enrolled patients that examined the impact of cardiac medical therapy on outcomes ≥1 year after CABG. The MEDLINE database was searched for trials conducted between 1966 and 2004 on the following medications: aspirin, antilipid agents, beta-blockers, calcium channel blockers (CCBs), nitrates, and angiotensin-converting enzyme (ACE) inhibitors. Both aspirin and antilipid agents were found to reduce the progression of atherosclerosis and the occurrence of graft occlusion. Cardiovascular events were decreased with antilipid agents. In small trials, beta-blockers and CCBs failed to decrease the incidence of cardiovascular events. No RCTs examined nitrates, and one small RCT documented a reduction in cardiovascular events among patients treated with ACE inhibitors. We conclude that few RCTs have examined the efficacy of cardiac medical therapy in post-CABG patients. Based on current RCT evidence, aspirin and antilipid agents should be used routinely after CABG. However, current data do not support the use of beta-blockers, CCBs, and nitrates, and more evidence is needed regarding the use of ACE inhibitors.
 

Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds A meta-analysis of randomized controlled trials

Objectives The aim of this research was to estimate the efficacy and safety of current high-density lipoprotein cholesterol (HDL-C)-increasing drugs.
Background Epidemiologic evidence has shown that HDL-C is inversely related to coronary heart disease (CHD) risk. However, the evidence for reducing CHD risk by raising HDL-C is thin, predominantly due to the paucity of effective and safe HDL-increasing drugs.
Methods Randomized controlled trials with fibrates and niacin, published between 1966 through February 2004 (MEDLINE), were retrieved. Information on treatment, baseline characteristics, serum lipids, end points, and side-effects were independently abstracted by two authors using a standardized protocol.
Results Data from 53 trials (16,802 subjects) using fibrates and 30 trials (4,749 subjects) using niacin were included. Random-effects model showed 11% versus 10% reduction in total cholesterol, 36% versus 20% reduction in triglycerides, 8% versus 14% reduction in low-density lipoprotein cholesterol, and 10% versus 16% increase in HDL-C for fibrates and niacin, respectively. Apart from flushes in the niacin group, both fibrates and niacin were shown to be well-tolerated and safe. Fibrates reduced the risk for major coronary events by 25% (95% confidence interval 10% to 38%), whereas current available data for niacin indicate a 27% reduction.
Conclusions Fibrates reduce major coronary events and increase HDL-C levels without significant toxicity. Niacin has a more potent effect on HDL-C levels, whereas data on cardiovascular event rate reduction are limited. Future studies need to evaluate whether additional HDL increase by fibrates or particularly newer niacin formulations on top of statin therapy translates into further event reduction in high-risk subjects, without significant toxicity.
 

What resting heart rate should one aim for when treating patients with heart failure with a beta-blocker? Experiences from the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF)

Objectives The goal of this study was to explore the question: what resting heart rate (HR) should one aim for when treating patients with heart failure with a beta-blocker?
Background The interaction of pretreatment and achieved resting HR with the risk-reducing effect of beta-blocker treatment needs further evaluation.
Methods Cardiovascular risk and risk reduction were analyzed in five subgroups defined by quintiles (Q) of pretreatment resting HR in the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF).
Results Mean baseline HR in the 5 Qs were 71, 76, 81, 87, and 98 beats/min; achieved HR 63, 66, 68, 72, and 75 beats/min; and net change −8, −10, −11, −13, and −14 beats/min, respectively. Baseline HR was related to a number of baseline characteristics. Cardiovascular risk was no different in Q1 toQ 4 (placebo groups) but increased in Q5 (HR above 90 beats/min). No relationship was observed between the risk-reducing effect of metoprolol controlled release/extended release (CR/XL) and baseline HR in the five Qs of baseline HR, or achieved HR, or change in HR during follow-up, respectively.
Conclusions Metoprolol CR/XL significantly reduced mortality and hospitalizations independent of resting baseline HR, achieved HR, and change in HR. Achieved HR and change in HR during follow-up were closely related to baseline HR; therefore, it was not possible to answer the question posed. Instead, one has to apply a very simple rule: aim for the target beta-blocker dose used in clinical trials, and strive for the highest tolerated dose in all patients with heart failure, regardless of baseline and achieved HR.

Contribution of ischemic mitral regurgitation to congestive heart failure after myocardial infarction

Objectives The purpose of this study was to define the contribution of ischemic mitral regurgitation (IMR) to the occurrence of congestive heart failure (CHF) after myocardial infarction (MI).
Background After MI, CHF is a frequent and serious complication, but its determinants and, particularly, the role of IMR are poorly defined.
Methods We analyzed 173 asymptomatic patients with previous Q-wave MI (>16 days) with echocardiographic quantitation of IMR (measuring effective regurgitant orifice [ERO] and regurgitant volume). The 102 patients with IMR were matched to 71 patients without IMR for age (71 ± 11 years vs. 68 ± 9 years; p = 0.11), gender (76% vs. 82% males; p = 0.41), and left ventricular ejection fraction (EF) (37 ± 14% vs. 36 ± 11%; p = 0.92).
Results Five-year rates of CHF and of CHF or cardiac death (CD) were 36 ± 5% and 52 ± 5%, respectively. Independent determinants of CHF were EF, sodium plasma level, and presence and degree of IMR (p < 0.0001). Five-year CHF rates were 18 ± 5% without mitral regurgitation (MR), 53 ± 7% with IMR, 46 ± 9% with ERO 1 to 19 mm2 and 68 ± 12% with ERO ≥20 mm2 (all p < 0.0001). The adjusted relative risk of CHF was 3.65 (95% confidence interval [CI] 1.86 to 7.75) for IMR presence and 4.42 (95% CI 1.9 to 10.5) for ERO ≥20 mm2. The adjusted relative risk of CHF/CD was 2.97 (95% CI 1.77 to 5.16) for IMR presence and 4.4 (95% CI 2.4 to 8.2) for ERO ≥20 mm2.
Conclusions After MI, incidence of CHF and of CHF/CD are high even in patients with no or minimal symptoms at baseline and are higher in patients with IMR. Congestive heart failure is independently determined by larger ERO of IMR. These data suggest that detecting and quantifying IMR is essential for risk stratification after MI. Value of IMR treatment in improving post-MI outcome should be investigated.

A prospective randomized comparison between paclitaxel and sirolimus stents in the real world of interventional cardiology The TAXi trial

Objectives We conducted this trial to assess whether a sirolimus-eluting stent (SES) produces similar results to a paclitaxel-eluting stent (PES) when used in the real world of interventional cardiology.
Background Several drug-eluting stents have been shown to exert a beneficial effect on restenosis when used in the treatment of coronary artery disease. Any potential superiority of one drug over the others, however, is still unknown.
Methods To evaluate whether a PES or an SES is superior in daily practice, we randomized all patients suitable to receive a drug-eluting stent in our institution. Clinical follow-up was obtained after at least six months.
Results A total of 202 patients were included in this trial. One hundred patients received a PES and 102 received an SES. Procedural success was 99% in both groups. Incidence of major adverse cardiac events at follow-up (mean 7 ± 2 months) was 4% with the PES and 6% with the SES (p = 0.8). The need for target lesion revascularization was very low in both groups (1% with the PES and 3% with the SES).
Conclusions Our results confirm that the high success rate obtained with both stents in randomized trials can be replicated in routine clinical practice. In this small group of patients we were unable to show any advantage of one stent over the other.
 

Assessment of Markers for Identifying Patients at Risk for Life-Threatening Arrhythmic Events in Brugada Syndrome

Introduction: Risk stratification for life-threatening arrhythmic events in Brugada syndrome is not yet established. The aim of the present study was to examine the usefulness of various markers in predicting life-threatening arrhythmic events in the Brugada syndrome.
Methods and Results: Forty-six patients with Brugada-type ECGs were categorized into the symptomatic (n = 28) and asymptomatic (n = 18) groups. Statistical analyses were performed with respect to the usefulness of the following markers: SCN5A mutation, pharmacologic challenge, ventricular fibrillation (VF) inducibility by programmed electrical stimulation, and late potential (LP) by signal-averaged ECG (SAECG). Comparison between the two groups revealed a significant difference only in LP positivity (92.6% vs 47.1%, P = 0.0004). The symptomatic group had significantly lower RMS40, longer LAS40, and longer fQRSd compared with the asymptomatic group. A significant difference was noted, especially RMS40. The positive predictive value, negative predictive value, and predictive accuracy when setting a cutoff value of 15 V were 92.0%, 78.9%, and 86.4%, respectively. Furthermore, patients with an RMS40 value <15 V (n = 25) showed significantly higher rates of VF recurrence compared with patients with an RMS40 value 15 V (n = 19, P = 0.047).
Conclusion: Regarding risk stratification for identifying high-risk patients in Brugada syndrome, only LP by SAECG was shown to be useful, suggesting the importance of RMS40 in predicting the history of life-threatening arrhythmic events and the recurrence of VF.
 

Diagnostic Value of Nitrate Stimulated Tilt Testing Without Preceding Passive Tilt in Patients with Suspected Vasovagal Syncope and a Healthy Control Group

Background: The contribution of the passive tilt phase, in a combined nitrate stimulated tilt protocol may be low yielding. In order to develop a shortened, and thus easier to perform test, we investigated the optimal duration of a nitrate tilt protocol without a preceding passive phase.
Methods: Thirty-eight consecutive patients (18F/20M; mean age 46 ± 16) with clinically suspected vasovagal syncope and 31 control subjects (15F/16M; mean age 40 ± 18) were tested. The subjects were tilted to 70° for a maximum period of 30 minutes, and sublingual nitroglycerin 0.4 mg spray was administrated directly after attaining erect posture. Receiver operator characteristics (ROC) analysis was done to determine the optimal test duration.
Results: In the patient group 31 (82%) and in controls 5 (16%) had a positive test. Sensitivity, specificity, and accuracy at test end were 82, 84, and 83%, respectively. ROC analysis revealed that a maximum accuracy of 83% was attained at 14 minutes, with a sensitivity and specificity of 79 and 87%, respectively.
Conclusion: Nitrate stimulated tilt testing, without a preceding passive tilt phase, and limited to a test duration of 15 minutes, provides an accurate, sensitive, and specific method to provoke vasovagal reactions in subjects with clinically suspected vasovagal syncope.
 

Outflow tract tachycardia with R/S transition in lead V3. Six different anatomic approaches for successful ablation

Objectives The aim of this study was to analyze different anatomic mapping approaches for successful ablation of outflow tract tachycardia with R/S transition in lead V3.
Background Idiopathic ventricular tachycardia can originate from different areas in the outflow tract, including the right and left ventricular endocardium, the epicardium, the pulmonary artery, and the aortic sinus of Valsalva. Although electrocardiographic criteria may be helpful in predicting the area of origin, sometimes the focus is complex to determine, especially when QRS transition in precordial leads is in V3.
Methods We analyzed surface electrocardiograms of 33 successfully ablated patients with outflow tract tachycardia: 20 from the right ventricular outflow tract (RVOT) and 13 from different sites. The R/S transition was determined, and the different anatomic approaches needed for successful catheter ablation were studied.
Results Overall, R/S transition in lead V3 was present in 19 (58%) of all patients. In these patients, mapping was started and successfully completed in the RVOT in 11 of 19 (58%) patients. The remaining eight patients with R/S transition in lead V3 needed five additional anatomic accesses for successful ablation: from the left ventricular outflow tract (n = 3), aortic sinus of Valsalva (n = 2), coronary sinus (n = 1), the epicardium via pericardial puncture (n = 1), and the trunk of the pulmonary artery (n = 1), respectively.
Conclusions A R/S transition in lead V3 is common. In patients with outflow tract tachycardia with R/S transition in lead V3, a stepwise endocardial and epicardial mapping through up to six anatomic approaches can lead to successful radiofrequency catheter ablation.

Electrophysiological Characteristics of Junctional Rhythm During Ablation of the Slow Pathway in Different Types of Atrioventricular Nodal Reentrant Tachycardia

Background: Junctional rhythm (JR) is commonly observed during radiofrequency (RF) ablation of the slow pathway for atrioventricular (AV) nodal reentrant tachycardia. However, the atrial activation pattern and conduction time from the His-bundle region to the atria recorded during JR in different types of AV nodal reentrant tachycardia have not been fully defined.
Methods: Forty-five patients who underwent RF ablation of the slow pathway for AV nodal reentrant tachycardia were included; 27 patients with slow-fast, 11 patients with slow-intermediate, and 7 patients with fast-slow AV nodal reentrant tachycardia. The atrial activation pattern and HA interval (from the His-bundle potential to the atrial recording of the high right atrial catheter) during AV nodal reentrant tachycardia (HASVT) and JR (HAJR) were analyzed.
Results: In all patients with slow-fast AV nodal reentrant tachycardia, the atrial activation sequence recorded during JR was similar to that of the retrograde fast pathway, and transient retrograde conduction block during JR was found in 1 (4%) patient. The HAJR was significantly shorter than the HASVT (57 ± 24 vs 68 ± 21 ms, P < 0.01). In patients with slow-intermediate AV nodal reentrant tachycardia, the atrial activation sequence of the JR was similar to that of the retrograde fast pathway in 5 (45%), and to that of the retrograde intermediate pathway in 6 (55%) patients. Transient retrograde conduction block during JR was noted in 1 (9%) patient. The HAJR was also significantly shorter than the HASVT (145 ± 27 vs 168 ± 29 ms, P = 0.014). In patients with fast-slow AV nodal reentrant tachycardia, retrograde conduction with block during JR was noted in 7 (100%) patients. The incidence of retrograde conduction block during JR was higher in fast-slow AV nodal reentrant tachycardia than slow-fast (7/7 vs 1/11, P < 0.01) and slow-intermediate AV nodal reentrant tachycardia (7/7 vs 1/27, P < 0.01).
Conclusions: In patients with slow-fast and slow-intermediate AV nodal reentrant tachycardia, the JR during ablation of the slow pathway conducted to the atria through the fast or intermediate pathway. In patients with fast-slow AV nodal reentrant tachycardia, there was no retrograde conduction during JR. These findings suggested there were different characteristics of the JR during slow-pathway ablation of different types of AV nodal reentrant tachycardia.
 

QT Correction Methods in Children and Adolescents

Introduction: Accurate determination of the QTc interval has become increasingly important in the assessment of a drug's ability to prolong cardiac repolarization. Previous work suggests the most appropriate correction formula for adults is QTc = QT/RR0.40, but little on correction methods for children and adolescents has been published.
Methods and Results: In this study, ECG data were obtained from a meta-analysis of seven clinical trials for attention deficit/hyperactivity disorder (ADHD) involving 2,288 children and adolescents. The most appropriate formula for children and adolescents included in this database was found to be QTc = QT/RR0.38. Adjustments of the correction factor specifically for males and females of different ages also are reported.
Conclusion: QT correction methods developed for adults do not apply to children. As accurate QTc determination plays a larger role in assessing a drug's potential to retard repolarization, use of age- and gender-specific correction formulas becomes more important.
 

Repeated Dual External Direct Cardioversions Using Two Simultaneous 360-J Shocks for Refractory Atrial Fibrillation Are Safe and Effective

Failure of cardioversion of atrial fibrillation (AF) to sinus rhythm (SR) by standard external direct current cardioversion (DCC) may be due to failure of delivery of enough defibrillating energy rather than to the true refractoriness of AF. Ninety-nine patients with persistent AF (76 male; age 63.7 ± 0.4 years; weight 113.1 ± 25.1 kg) who failed standard DCC were included in this report. Under anesthesia, QRS synchronous shocks were delivered across anteroposterior electrodes in the following sequence: (1) a single 360-J shock; (2) another single 360-J shock within 2 minutes; (3) 30 minutes of rest, reinduction of anesthesia and delivery of two simultaneous monophasic 360-J shocks. All patients underwent all three DCC steps. Sixty-six (67%) patients converted to SR following the first dual simultaneous shock. Fourteen patients (14%) required more than one dual shock to achieve SR. This increased the overall success rate of resuming SR to 81%. Except for minor skin burns in three patients there were no procedure related complications. On follow-up at 1 month, 55 (56%) patients were still in SR, whereas 50 (51%) patients maintained SR at 12 months. This was similar to our general DCC population (55% of the 1698 patients were in SR 6 months post-DCC, P = ns). In conclusion, dual external monophasic 360-J DCC is an effective rescue technique for restoration of SR in patients with AF refractory to standard DCC. AF in these patients seems to be as amenable to chronic suppression as AF in the general population of DCC patients.

Long-Term Prognosis of Individuals With Right Precordial ST-Segment–Elevation Brugada Syndrome

Background— Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death as a result of ventricular fibrillation. Controversy exists with regard to risk stratification and therapeutic management, particularly in asymptomatic individuals.
Methods and Results— A total of 212 individuals (mean age, 45±6 years) with a type 1 Brugada ECG pattern were studied. Of these, 123 (58%) were asymptomatic, 65 (31%) had 1 syncope of unknown origin, and 24 (11%) had to be resuscitated because of ventricular fibrillation. In 125 individuals (59%), a spontaneous type 1 ECG was recorded. In the remaining, drug challenge with a class I antiarrhythmic agent unmasked a Brugada ECG. The mean ST elevation was 2.3±1.2 mm in symptomatic patients and 1.9±1.5 mm in asymptomatic individuals (P=0.04). During a mean follow-up of 40±50 months, 4 of the 24 patients (17%) with aborted sudden cardiac death and 4 of 65 (6%) with a prior syncope had a recurrent arrhythmic event, whereas only 1 of 123 asymptomatic individuals (0.8%) had a first arrhythmic event. Four of 9 patients with arrhythmic events during follow-up were not inducible during programmed electrical stimulation. A previous history of aborted sudden death or syncope and the presence of a spontaneous type 1 ECG were predictors of adverse outcome.
Conclusions— The present study reports data on a large population of individuals with a type 1 Brugada ECG pattern with the longest follow-up reported so far. A very low incidence of severe arrhythmic events, particularly in asymptomatic individuals, was found during follow-up. In the presence of very few arrhythmic events on follow-up, programmed electrical stimulation showed very little accuracy in predicting outcome.


 

Statin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery Disease

Background Recent trials have demonstrated better outcomes with intensive than with moderate statin treatment. Intensive treatment produced greater reductions in both low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP), suggesting a relationship between these two biomarkers and disease progression.
Methods We performed intravascular ultrasonography in 502 patients with angiographically documented coronary disease. Patients were randomly assigned to receive moderate treatment (40 mg of pravastatin orally per day) or intensive treatment (80 mg of atorvastatin orally per day). Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Lipoprotein and CRP levels were measured at baseline and follow-up.
Results In the group as a whole, the mean LDL cholesterol level was reduced from 150.2 mg per deciliter (3.88 mmol per liter) at baseline to 94.5 mg per deciliter (2.44 mmol per liter) at 18 months (P<0.001), and the geometric mean CRP level decreased from 2.9 to 2.3 mg per liter (P<0.001). The correlation between the reduction in LDL cholesterol levels and that in CRP levels was weak but significant in the group as a whole (r=0.13, P=0.005), but not in either treatment group alone. In univariate analyses, the percent change in the levels of LDL cholesterol, CRP, apolipoprotein B-100, and non–high-density lipoprotein cholesterol were related to the rate of progression of atherosclerosis. After adjustment for the reduction in these lipid levels, the decrease in CRP levels was independently and significantly correlated with the rate of progression. Patients with reductions in both LDL cholesterol and CRP that were greater than the median had significantly slower rates of progression than patients with reductions in both biomarkers that were less than the median (P=0.001).
Conclusions For patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP.
 

C-Reactive Protein Levels and Outcomes after Statin Therapy

Background Statins lower the levels of low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP). Whether this latter property affects clinical outcomes is unknown.
Methods We evaluated relationships between the LDL cholesterol and CRP levels achieved after treatment with 80 mg of atorvastatin or 40 mg of pravastatin per day and the risk of recurrent myocardial infarction or death from coronary causes among 3745 patients with acute coronary syndromes.
Results Patients in whom statin therapy resulted in LDL cholesterol levels of less than 70 mg per deciliter (1.8 mmol per liter) had lower event rates than those with higher levels (2.7 vs. 4.0 events per 100 person-years, P=0.008). However, a virtually identical difference was observed between those who had CRP levels of less than 2 mg per liter after statin therapy and those who had higher levels (2.8 vs. 3.9 events per 100 person-years, P=0.006), an effect present at all levels of LDL cholesterol achieved. For patients with post-treatment LDL cholesterol levels of more than 70 mg per deciliter, the rates of recurrent events were 4.6 per 100 person-years among those with CRP levels of more than 2 mg per liter and 3.2 events per 100 person-years among those with CRP levels of less than 2 mg per liter; the respective rates among those with LDL cholesterol levels of less than 70 mg per deciliter were 3.1 and 2.4 events per 100 person-years (P<0.001). Although atorvastatin was more likely than pravastatin to result in low levels of LDL cholesterol and CRP, meeting these targets was more important in determining the outcomes than was the specific choice of therapy. Patients who had LDL cholesterol levels of less than 70 mg per deciliter and CRP levels of less than 1 mg per liter after statin therapy had the lowest rate of recurrent events (1.9 per 100 person-years).
Conclusions Patients who have low CRP levels after statin therapy have better clinical outcomes than those with higher CRP levels, regardless of the resultant level of LDL cholesterol. Strategies to lower cardiovascular risk with statins should include monitoring CRP as well as cholesterol.
 

Long-Term Prognosis of Individuals With Right Precordial ST-Segment-Elevation Brugada Syndrome

Background--Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death as a result of ventricular fibrillation. Controversy exists with regard to risk stratification and therapeutic management, particularly in asymptomatic individuals.
Methods and Results--A total of 212 individuals (mean age, 45±6 years) with a type 1 Brugada ECG pattern were studied. Of these, 123 (58%) were asymptomatic, 65 (31%) had 1 syncope of unknown origin, and 24 (11%) had to be resuscitated because of ventricular fibrillation. In 125 individuals (59%), a spontaneous type 1 ECG was recorded. In the remaining, drug challenge with a class I antiarrhythmic agent unmasked a Brugada ECG. The mean ST elevation was 2.3±1.2 mm in symptomatic patients and 1.9±1.5 mm in asymptomatic individuals (P=0.04). During a mean follow-up of 40±50 months, 4 of the 24 patients (17%) with aborted sudden cardiac death and 4 of 65 (6%) with a prior syncope had a recurrent arrhythmic event, whereas only 1 of 123 asymptomatic individuals (0.8%) had a first arrhythmic event. Four of 9 patients with arrhythmic events during follow-up were not inducible during programmed electrical stimulation. A previous history of aborted sudden death or syncope and the presence of a spontaneous type 1 ECG were predictors of adverse outcome.
Conclusions--The present study reports data on a large population of individuals with a type 1 Brugada ECG pattern with the longest follow-up reported so far. A very low incidence of severe arrhythmic events, particularly in asymptomatic individuals, was found during follow-up. In the presence of very few arrhythmic events on follow-up, programmed electrical stimulation showed very little accuracy in predicting outcome.

Transcatheter cryoablation of tachyarrhythmias in children Initial experience from an international registry

Objectives We sought to describe the early pediatric experience of transcatheter cryoablation, and identify whether specific arrhythmia substrates and/or ablation locations were particularly suited to cryoablation.
Background Radiofrequency (RF) ablation has become established therapy for pediatric tachyarrhythmias. However, challenges remain in terms of the safety and efficacy of RF ablation in specific locations; new methods may address these issues.
Methods Prospective data were available for 64 patients age 13 ± 4 (mean ± SD) years undergoing cryoablation at 14 centers participating in the Cryocath International Patient Registry. Dysrhythmia duration was 5.0 ± 4.2 years, with diagnoses of atrioventricular node re-entrant tachycardia (AVNRT) (n = 30), anteroseptal (n = 11), midseptal (n = 5), or other (n = 15) accessory pathway (AP) mediated AV re-entry, ventricular tachycardia (VT) (n = 3), and ectopic atrial tachycardia (EAT) (n = 2). Two patients had more than one arrhythmia substrate. Transcatheter cryoablation was offered by cardiologist preference after written informed procedural consent of each patient and/or legal guardian. Cryomapping was performed at −30°C and cryoablation was delivered with 4-min applications at −75°C.
Results Acute success was achieved in 45 of 65 (69%) cryoablation patients, with best success rates in AVNRT (83%) and right septal AP (75%), and lower success rates in other AP (43%), VT (66%), and EAT (0%). No device-related adverse events were reported. The success of radiofrequency (RF) ablation applied in 14 cryoablation failures was 4 of 4 for AVNRT patients, 1 of 1 for anteroseptal AP patients, 5 of 6 for other AP patients, 0 of 1 for VT patients, and 0 of 2 for EAT patients.
Conclusions Transcatheter cryoablation is a safe and well-tolerated alternative to RF ablation in pediatric patients on the basis of our initial experience. Success is highest in AVNRT and in substrates recognized as technically challenging or risky for RF ablation.
 

 
Cost-Effectiveness of Dual-Chamber Pacing Compared With Ventricular Pacing for Sinus Node Dysfunction

Background--Compared with single-chamber ventricular pacing, dual-chamber pacing can reduce adverse events and, as a result, improve quality of life in patients paced for sick sinus syndrome. It is not clear, however, how these benefits compare with the increased cost of dual-chamber pacemakers.
Methods and Results--We used 4-year data from a 2010-patient, randomized trial to estimate the incremental cost-effectiveness of dual-chamber pacing compared with ventricular pacing and then projected these findings over the patients’ lifetimes by using a Markov model that was calibrated to the first 5 years of in-trial data. To assess the stability of the findings, we performed 1000 bootstrap analyses and multiple sensitivity analyses. During the first 4 years of the trial, dual-chamber pacemakers increased quality-adjusted life expectancy by 0.013 year per subject at an incremental cost-effectiveness ratio of $53 000 per quality-adjusted year of life gained. Over a lifetime, dual-chamber pacing was projected to increase quality-adjusted life expectancy by 0.14 year with an incremental cost-effectiveness ratio of $6800 per quality-adjusted year of life gained. In bootstrap analyses, dual-chamber pacing was cost-effective in 91.9% of simulations at a threshold of $50 000 per quality-adjusted year of life and in 93.2% of simulations at a threshold of $100 000. Its cost-effectiveness ratio was also below this threshold in numerous sensitivity analyses that varied key estimates.
Conclusions--For patients with sick sinus syndrome requiring pacing, dual-chamber pacing increases quality-adjusted life expectancy at a cost that is generally considered acceptable.

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