Impact of atrial prevention pacing on atrial fibrillation burden: primary results of the Study of Atrial Fibrillation Reduction (SAFARI) trial.

BACKGROUND: The role of atrial-based pacing algorithms in preventing atrial fibrillation (AF) remains controversial. The inconsistent results noted in previous trials may be due in part to differences in endpoints, pacing algorithms, and study design. SAFARI, a worldwide, prospective, randomized clinical trial, was designed to address these issues and to evaluate the safety and efficacy of a suite of prevention pacing therapies (PPTs) among patients with paroxysmal AF. METHODS AND RESULTS: Patients who met standard pacemaker indications and documented symptomatic AF were implanted with a pacemaker (Vitatron Selection 9000). At 4 months, only patients with documented AF despite dual-chamber pacing were randomized to PPTs ON or PPTs OFF and followed for 6 months. Incidence of permanent AF and change in AF burden were compared between the two groups. Among the 555 patients enrolled, 240 had AF burden at 4 months and were randomized. The risk of developing permanent AF was similar in both groups (0 in the PPTs ON group vs. 3 in the OFF group). However, there was a significant reduction in AF burden between baseline and 10-month follow-up in the ON group compared with the OFF group (median decrease of 0.08 hours/day vs no change, P = .03). CONCLUSION: Among patients with paroxysmal AF and standard bradycardia indications, PPTs are safe and associated with less AF burden compared with conventional pacing.

Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy.

OBJECTIVES: This study sought to assess whether implantable cardioverter-defibrillators (ICDs) have different mortality benefits among patients with ischemic cardiomyopathy who screen negative and non-negative (positive and indeterminate) for microvolt T-wave alternans (MTWA). BACKGROUND: Microvolt T-wave alternans has been proposed as an effective tool for risk stratification. However, no studies have examined whether ICD benefits differ by MTWA group. METHODS: We developed a prospective cohort of 768 patients with ischemic cardiomyopathy (left ventricular ejection fraction < or =35%) and no prior sustained ventricular arrhythmia, of which 392 (51%) received ICDs. The mean follow-up time was 27 +/- 12 months. Propensity scores for ICD implantation based on the variables most likely to influence defibrillator implantation were developed for each MTWA cohort. Multivariable Cox analyses that controlled for propensity score, demographics, and clinical variables evaluated the degree to which ICDs decreased mortality risk for each MTWA group. RESULTS: We identified 514 (67%) patients with a non-negative MTWA test result. After multivariable adjustment, ICDs were associated with lower all-cause mortality in MTWA-non-negative patients (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.27 to 0.76, p = 0.003) but not in MTWA-negative patients (HR 0.85, 95% CI 0.33 to 2.20, p = 0.73) (for interaction, p = 0.04), with the mortality benefit in MTWA-non-negative patients largely mediated through arrhythmic mortality reduction (HR 0.30, 95% CI 0.13 to 0.68, p = 0.004). The number needed to treat with an ICD for 2 years to save 1 life was 9 among MTWA-non-negative patients and 76 among MTWA-negative patients. CONCLUSIONS: In patients with ischemic cardiomyopathy and no prior history of ventricular arrhythmia, mortality reduction with ICD implantation differs by MTWA status, with implications for risk stratification and health policy.

Effectiveness of implantable cardioverter-defibrillators in patients with ischemic heart disease and left ventricular dysfunction.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) have been shown in primary prevention efficacy trials to reduce mortality in patients with ischemic heart disease and left ventricular dysfunction. To investigate the generalizabilty of this mortality reduction, we examined the effectiveness of ICDs in clinical practice. METHODS: We developed a prospective multicenter cohort of 770 patients with ischemic left ventricular dysfunction (ejection fraction < or =35%) and without a history of ventricular arrhythmia, of whom 395 (52%) received ICDs. Mean +/- SD follow-up was 27 +/- 12 months. We assessed the degree to which ICDs decreased mortality risk using Cox proportional hazards analyses that controlled for clinical predictors of death, receipt of ICD (a propensity score analysis), and predictors of arrhythmic death (including electrophysiologic variables). RESULTS: Multivariate Cox analyses showed that those with ICDs had significantly lower all-cause mortality (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.33-0.86). This mortality reduction was mediated through dramatically lower arrhythmia-related mortality (HR, 0.35; 95% CI, 0.17-0.73), with no significant effect on cardiovascular nonarrhythmic (HR, 0.81; 95% CI, 0.34-1.96) and noncardiovascular (HR, 0.76; 95% CI, 0.29-2.05) mortality. No differences were found between the ICD and non-ICD groups for a composite outcome of all-cause mortality, appropriate ICD shocks, or documented symptomatic ventricular arrhythmia, which suggests that the 2 groups had similar baseline risk for life-threatening arrhythmic events (HR, 0.96; 95% CI, 0.63-1.45). CONCLUSION: In clinical practice, ICDs appear to reduce all-cause and arrhythmic rates of mortality at levels similar to those found in primary prevention trials.

Prognostic utility of microvolt T-wave alternans in risk stratification of patients with ischemic cardiomyopathy.

OBJECTIVES: The purpose of this study was to assess if microvolt T-wave alternans (MTWA) is an independent predictor of mortality in patients with ischemic cardiomyopathy. BACKGROUND: Microvolt T-wave alternans has been proposed as an effective tool for identifying high-risk patients with ischemic cardiomyopathy who are likely to benefit from implantable cardioverter-defibrillator (ICD) therapy. However, earlier studies have been limited in their ability to control for baseline differences between MTWA-negative and -non-negative (positive and indeterminate) patients. METHODS: We enrolled 768 consecutive patients with ischemic cardiomyopathy (left ventricular ejection fraction < or =35%) and no prior history of ventricular arrhythmia. All patients underwent baseline MTWA testing and were classified as MTWA negative or non-negative. Multivariable Cox regression analyses, stratified by ICD status, were used to determine the association between MTWA testing and mortality after adjusting for demographic, clinical, and treatment differences between MTWA-negative and -non-negative patients. RESULTS: We identified 514 (67%) patients with a non-negative MTWA test. After multivariable adjustment, a non-negative MTWA test was associated with a significantly higher risk for all-cause (stratified hazard ratio [HR] = 2.24 [95% confidence interval 1.34 to 3.75]; p = 0.002) and arrhythmic mortality (stratified HR = 2.29 [1.00 to 5.24]; p = 0.049) but not for nonarrhythmic mortality (stratified HR = 1.77 [0.84 to 3.74]; p = 0.13). In subgroup analyses, a non-negative MTWA test was also associated with a higher risk for all-cause mortality in patients with ejection fractions < or =30% (stratified HR = 2.10 [1.18 to 3.73]; p = 0.01) and after excluding those with indeterminate MTWA tests (stratified HR = 2.08 [1.18 to 3.66]; p = 0.01). CONCLUSIONS: Microvolt T-wave alternans is a strong and independent predictor of all-cause and arrhythmic mortality in patients with ischemic cardiomyopathy.

Combined efficacy of atrial septal lead placement and atrial pacing algorithms for prevention of paroxysmal atrial tachyarrhythmia.

INTRODUCTION: The combined role of atrial septal lead location and atrial pacing algorithms in the prevention of atrial tachyarrhythmias (AT/AF), including both atrial fibrillation and flutter, is unknown. We tested the hypothesis that atrial prevention pacing algorithms could decrease AT/AF frequency in patients with atrial septal leads, bradycardia, and paroxysmal AT/AF. METHODS AND RESULTS: A total of 298 patients (age 70 +/- 10 years; 61% male) from 35 centers were implanted with a DDDRP pacing system including three AT/AF prevention pacing algorithms. Lead site was randomized at implant to right atrial septal or nonseptal. Patients were randomized 1 month postimplant to AT/AF prevention ON or OFF for 3 months and then crossed over for 3 months. Patients logged symptomatic AT/AF episodes via a manual activator. Prevention efficacy was evaluated based on intention-to-treat in 277 patients (138 septal) with complete follow-up. No changes in device-recorded AT/AF frequency or burden were observed with algorithms OFF versus ON or between patients randomized to septal versus nonseptal lead location. Analysis of other secondary outcomes revealed that AT/AF prevention pacing resulted in decreased atrial premature contractions in both the septal (1.9 [0.2-8.7] vs 3.3 [0.3-10.6]x 103/day; P < 0.01) and nonseptal groups (0.9 [0.2-3.3] vs 1.3 [0.3-5.5]x 103/day; P < 0.001). Patients with septal leads had fewer symptomatic AT/AF episodes ON versus OFF (1.4 +/- 3.0 vs 2.5 +/- 5.2/month, P = 0.01). CONCLUSION: The combination of three atrial prevention pacing algorithms did not decrease device classified atrial tachyarrhythmia frequency or burden during a 3-month cross-over period in bradycardic patients and septal or nonseptal atrial pacing leads. Prevention pacing was associated with decreased frequency of premature atrial contractions and with decreased symptomatic atrial tachyarrhythmia frequency in patients with atrial septal leads.