Comparative study of acute and mid-term complications with leadless and transvenous cardiac pacemakers.

BACKGROUND: Leadless cardiac pacemakers (LCPs) aim to mitigate lead- and pocket-related complications seen with transvenous pacemakers (TVPs). OBJECTIVE: The purpose of this study was to compare complications between the LCP cohort from the LEADLESS Pacemaker IDE Study (Leadless II) trial and a propensity score-matched real-world TVP cohort. METHODS: The multicenter LEADLESS II trial evaluated the safety and efficacy of the Nanostim LCP (Abbott, Abbott Park, IL) using structured follow-up, with serious adverse device effects independently adjudicated. TVP data were obtained from Truven Health MarketScan claims databases for patients implanted with single-chamber TVPs between April 1, 2010 and March 31, 2014 and more than 1 year of preimplant enrollment data. Comorbidities and complications were identified via International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Short-term (≤1 months) and mid-term (>1-18 months) complications were compared between the LCP cohort and a propensity score-matched subset of the TVP cohort. RESULTS: Among 718 patients with LCPs (mean age 75.6 ± 11.9 years; 62% men) and 1436 patients with TVPs (mean age 76.1 ± 12.3 years; 63% men), patients with LCPs experienced fewer complications (hazard ratio 0.44; 95% confidence interval 0.32-0.60; P < .001), including short-term (5.8% vs 9.4%; P = .01) and mid-term (0.56% vs 4.9%; P < .001) events. In the short-term time frame, patients with LCPs had more pericardial effusions (1.53% vs 0.35%; P = .005); similar rates of vascular events (1.11% vs 0.42%; P = .085), dislodgments (0.97% vs 1.39%; P = .54), and generator complications (0.70% vs 0.28%; P = .17); and no thoracic trauma compared to patients with TVPs (rate of thoracic trauma 3.27%). In short- and mid-term time frames, TVP events absent from the LCP group included lead-related, pocket-related, and infectious complications. CONCLUSION: Patients with LCPs experienced fewer overall short- and mid-term complications, including infectious and lead- and pocket-related events, but more pericardial effusions, which were uncommon but serious.

Surveillance of AF recurrence post-surgical AF ablation using implantable cardiac monitor.

BACKGROUND: Although pulmonary vein isolation is an effective treatment for recurrent atrial fibrillation (AF), there is no consensus on the definition of success or follow-up strategies. Existing data are limited to intermittent Holter or transtelephonic monitoring with reliance on patient symptoms. OBJECTIVE: We sought to determine the outcomes of surgical ablation and post-ablation AF surveillance with a leadless implantable cardiac monitor (ICM). METHODS: Forty-five patients with drug-refractory paroxysmal or persistent AF underwent video-assisted epicardial ablation using a bipolar radiofrequency clamp. An ICM was implanted subcutaneously post-ablation to assess AF recurrence. AF recurrence was defined as ≥1 AF episode with a duration of ≥30 s. The device-stored data was downloaded weekly over the internet, and all transmitted events were reviewed. RESULTS: A total of 1,220 AF automatic and patient-activated AF episodes were analyzed over a follow-up of 12 ± 3 months. Of these episodes, 46% were asymptomatic. Furthermore, only 66% of the patient-activated episodes were AF. AF recurrence was highest in first 4 weeks and substantially decreased 6 months post-ablation. The overall freedom from AF recurrence at the end of follow-up was 60%. When 48-h Holter recordings were compared with the device-stored episodes, the sensitivity of the device to detect AF was 98%, and the specificity was 71%. CONCLUSIONS: The ICM provides an objective measure of AF ablation success and may be useful in making clinical decisions. This device may be used in future ablation studies to develop a more rigorous definition of procedural success.

Programming antitachycardia pacing for primary prevention in patients with implantable cardioverter defibrillators: results from the PROVE trial.

OBJECTIVES: the PROVE trial was designed to determine if antitachycardia pacing (ATP) is clinically beneficial for primary prevention in patients who have implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds). BACKGROUND: use of ICDs and CRT-Ds reduces mortality in patients with ventricular dysfunction and mild to moderate heart failure. However, in studies of the primary prevention population, shock-only ICDs are predominantly used, without ATP programming for less painful termination of ventricular tachycardia (VT). METHODS: we conducted a prospective, nonrandomized, multicenter study using market-released ICDs and CRT-Ds. Patients received devices programmed to deliver ATP for VT cycle lengths of 270-330 ms. Follow-up evaluation was performed at 3, 6, and 12 months. The incidence of VT and the rate of successful termination by ATP were analyzed. RESULTS: of 830 patients in the study population (men, 73%; mean age, 67.3 ± 12 years), 32% received single-chamber ICDs, 44% dual-chamber ICDs, and 24% CRT-Ds. ATP was attempted for 112 VT episodes in 71 patients, and 103 (92%) of the VT episodes were successfully terminated. Three VT episodes were accelerated by ATP and required termination by ICD shock; 6 episodes terminated spontaneously or by ICD shock. CONCLUSIONS: VT is common in patients without a history of this arrhythmia who have received ICDs or CRT-Ds for primary prevention indications. Programming ICDs for ATP therapy at the time of implantation could potentially terminate most VT episodes and reduce the number of painful shocks for these patients.

Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction: primary results from the T-wave alternans sudden cardiac death in heart failure trial substudy.

BACKGROUND: Sudden cardiac death remains a leading cause of mortality despite advances in medical treatment for the prevention of ischemic heart disease and heart failure. Recent studies showed a benefit of implantable cardioverter defibrillator implantation, but appropriate shocks for ventricular tachyarrhythmias were noted only in a minority of patients during 4 to 5 years of follow-up. Accordingly, better risk stratification is needed to optimize patient selection. In this regard, microvolt T-wave alternans (TWA) has emerged as a potentially useful measure of arrhythmia vulnerability, but it has not been evaluated previously in a prospective, randomized trial of implantable cardioverter defibrillator therapy. METHODS AND RESULTS: This investigation was a prospective substudy of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) that included 490 patients at 37 clinical sites. TWA tests were classified by blinded readers as positive (37%), negative (22%), or indeterminate (41%) by standard criteria. The composite primary end point was the first occurrence of any of the following events: sudden cardiac death, sustained ventricular tachycardia/fibrillation, or appropriate implantable cardioverter defibrillator discharge. During a median follow-up of 30 months, no significant differences in event rates were found between TWA-positive or -negative patients (hazard ratio 1.24, 95% confidence interval 0.60 to 2.59, P=0.56) or TWA-negative and nonnegative (positive and indeterminate) subjects (hazard ratio 1.28, 95% confidence interval 0.65 to 2.53, P=0.46). Similar results were obtained with the inclusion or exclusion of patients randomized to amiodarone in the analyses. CONCLUSIONS: TWA testing did not predict arrhythmic events or mortality in SCD-HeFT, although a small reduction in events (20% to 25%) among TWA-negative patients cannot be excluded given the sample size of this study. Accordingly, these results suggest that TWA is not useful as an aid in clinical decision making on implantable cardioverter defibrillator therapy among patients with heart failure and left ventricular systolic dysfunction.

Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial.

BACKGROUND: The present study assessed the efficacy and safety of vernakalant hydrochloride (RSD1235), a novel compound, for the conversion of atrial fibrillation (AF). METHODS AND RESULTS: Patients were randomized in a 2:1 ratio to receive vernakalant or placebo and were stratified by AF duration of 3 hours to 7 days (short duration) and 8 to 45 days (long duration). A first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes, followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if AF was not terminated. The primary end point was conversion of AF to sinus rhythm for at least 1 minute within 90 minutes of the start of drug infusion in the short-duration AF group. A total of 336 patients were randomized and received treatment (short duration, n=220; long duration, n=116). Of the 145 vernakalant patients, 75 (51.7%) in the short-duration AF group converted to sinus rhythm (median time, 11 minutes) compared with 3 of the 75 placebo patients (4.0%; P<0.001). Overall, in the short- and long-duration AF groups, 83 of the 221 vernakalant patients (37.6%) experienced termination of AF compared with 3 of the 115 placebo patients (2.6%; P<0.001). Transient dysgeusia and sneezing were the most common side effects in vernakalant-treated patients. Four vernakalant-related serious adverse events (hypotension [2 events], complete atrioventricular block, and cardiogenic shock) occurred in 3 patients. CONCLUSIONS: Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated.

Statin use was associated with reduced mortality in both ischemic and nonischemic cardiomyopathy and in patients with implantable defibrillators: mortality data and mechanistic insights from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

BACKGROUND: Recent observations suggest statin treatment may be associated with lower mortality in heart failure (HF). The SCD-HeFT was a study of 2521 functional class II and III HF patients with left ventricular ejection fractions < or = 35% and ischemic and nonischemic cardiomyopathy followed up for a median of 45.5 months. The study length, size, and degree of background HF, including the use of implantable defibrillator therapy, provide a unique opportunity to evaluate the impact of statin use in HF with mechanistic insights from subgroup analyses. METHODS AND RESULTS: Statin use was reported in 965 (38%) of 2521 patients at baseline and 1187 (47%) at last follow-up. The relationships between statin use, randomization arm, disease category, and functional class and all cause mortality were assessed. Statin use was studied as a time-dependent covariate in a multivariable Cox proportional hazards model, adjusted for imbalances between statin and no-statin groups. Mortality risk was significantly lower in those taking a statin (HR [95% CI], 0.70 [0.58-0.83]). Mortality risk was lower with statin use in all prespecified subgroups: ischemic cardiomyopathy (0.69 [0.56-0.86]), nonischemic cardiomyopathy (0.67 [0.47-0.96]), implantable cardioverter defibrillator (ICD) (0.66 [0.46-0.95], non-ICD (0.71 [0.57-0.87]), New York Heart Association II (0.62 [0.48-0.79]), and New York Heart Association III (0.79 [0.61-1.03]). CONCLUSIONS: Statin use is associated with reduced all-cause mortality in HF patients. Statins appear to benefit patients with nonischemic and ischemic cardiomyopathy similarly. Statin benefits are similar in ICD and non-ICD patients.

Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.

BACKGROUND: Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter-defibrillator (ICD) has been proposed to improve the prognosis in such patients. METHODS: We randomly assigned 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end point was death from any cause. RESULTS: The median LVEF in patients was 25 percent; 70 percent were in NYHA class II, and 30 percent were in class III CHF. The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent. The median follow-up was 45.5 months. There were 244 deaths (29 percent) in the placebo group, 240 (28 percent) in the amiodarone group, and 182 (22 percent) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53) and ICD therapy was associated with a decreased risk of death of 23 percent (0.77; 97.5 percent confidence interval, 0.62 to 0.96; P=0.007) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. Results did not vary according to either ischemic or nonischemic causes of CHF, but they did vary according to the NYHA class. CONCLUSIONS: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.

A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation.

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of intravenous RSD1235 in terminating recent onset atrial fibrillation (AF). BACKGROUND: Anti-arrhythmic drugs currently available to terminate AF have limited efficacy and safety. RSD1235 is a novel atrial selective anti-arrhythmic drug. METHODS: This was a phase II, multi-centered, randomized, double-blinded, step-dose, placebo-controlled, parallel group study. Fifty-six patients from 15 U.S. and Canadian sites with AF of 3 to 72 h duration were randomized to one of two RSD1235 dose groups or to placebo. The two RSD1235 groups were RSD-1 (0.5 mg/kg followed by 1 mg/kg) or RSD-2 (2 mg/kg followed by 3 mg/kg), by intravenous infusion over 10 min; a second dose was given only if AF was present. The primary end point was termination of AF during infusion or within 30-min after the last infusion. Secondary end points included the number of patients in sinus rhythm at 0.5, 1, and 24 h post-last infusion and time to conversion to sinus rhythm. RESULTS: The RSD-2 dose showed significant differences over placebo in: 1) termination of AF (61% vs. 5%, p < 0.0005); 2) patients in sinus rhythm at 30 min (56% vs. 5%, p < 0.001); 3) sinus rhythm at 1 h (53% vs. 5%, p = 0.0014); and 4) median time to conversion to SR (14 vs. 162 min, p = 0.016). There were no serious adverse events related to RSD1235. CONCLUSIONS: RSD1235, a new atrial-selective anti-arrhythmic agent, appears to be efficacious and safe for converting recent onset AF to sinus rhythm.

Implantable cardioverter defibrillator therapy in patients with ischemic or non-ischemic cardiomyopathy and nonsustained ventricular tachycardia.

BACKGROUND: Mortality benefit from implantable cardioverter defibrillator (ICD) therapy in ischemic cardiomyopathy (ICM) with non-sustained ventricular tachycardia (NS-VT) and inducible VT is well defined. Although NS-VT may suggest an increased risk of sudden cardiac death (SCD) in non-ischemic cardiomyopathy (NICM), the role of ICD therapy is unclear. This retrospective study compares follow-up data in these two groups after ICD implantation. METHODS: 153 consecutive patients with ICD implantation for NS-VT were analyzed. ICM patients received an ICD if they had inducible VT at electrophysiology study (EPS). NICM patients did not routinely undergo EPS before ICD implantation. RESULTS: There were 48 patients (33 males) in NICM group and 105 patients (89 males) in the ICM group. Baseline characteristics including mean ejection fraction (EF), distribution in various New York Heart Association (NYHA) classes, and the mean duration of follow up in the two groups were similar. 50% of the patients in the NICM group and 36% in the ICM group received appropriate therapies (p = 0.106). The mean number of appropriate therapies in the two groups were similar (23.3 +/- 56.7 and 22.5 +/- 59.5 respectively, p = NS). The percentage of patients with inappropriate therapies in the two groups were 27% and 23% respectively (p = NS). Patients in the NICM group received appropriate ICD discharges at a greater rate (p = 0.02). CONCLUSION: Patients undergoing ICD implantation for NICM and NS-VT receive appropriate ICD therapy at a greater rate than those implanted for ICM, NS-VT, and a positive EPS. Although these data do not prove survival benefit in NICM, they suggest a beneficial effect.

The impact of atrial prevention and termination therapies on atrial tachyarrhythmia burden in patients receiving a dual-chamber defibrillator for ventricular arrhythmias.

INTRODUCTION: This prospective, multicenter, randomized trial evaluated the effects of atrial prevention and termination therapies on atrial tachyarrhythmia (ATA) burden in patients with a standard indication for an implantable cardioverter defibrillator (ICD). METHODS: A Jewel AF or GEM III AT ICD was implanted in 451 patients. At 1-month post-implant, patients were randomized to atrial prevention and termination therapies ON ( n = 199) or OFF ( n = 206) and followed for 6 additional months. Automatic atrial shocks were enabled in only 14% of the ON group. The follow-up time after randomization was 6.9 +/- 2.4 months ON versus 6.8 +/- 2.3 months OFF. RESULTS: There were 126/405 (31.1%) patients who had AT/AF episodes during follow-up. Only four patients received a shock to treat ATA's during follow-up. The median ATA burden was 0 hours/month in both the ON and OFF groups ( P = 0.40). The mean ATA burden was 4.3 +/- 20.0 hours/month ON versus 9.0 +/- 50.0 hours/month OFF ( P = 0.11). In a subgroup of 192 patients with a history of ATA's, the median burden was 0 hours/month in the both groups ( P = 0.23). However, the mean burden in this subgroup was 7.6 +/- 27.1 hours/month ON versus 19.2 +/- 73.7 hours/month OFF ( P = 0.056). CONCLUSIONS: In patients receiving an ICD for ventricular arrhythmias, no significant change in ATA burden was observed when atrial prevention and termination therapies were enabled. This may have been due to the low ATA burden in this population. In a subgroup of patients with history of ATA's, there was a trend towards a reduction in mean burden.