Comparative Effectiveness of Left Atrial Appendage Occlusion Versus Oral Anticoagulation by Sex.

BACKGROUND: The comparative real-world outcomes of older patients with atrial fibrillation (AF) treated with anticoagulation compared with left atrial appendage occlusion (LAAO) may be different from those in clinical trials because of differences in anticoagulation strategies and patient demographics, including a greater proportion of women. We sought to compare real-world outcomes between older patients with AF treated with anticoagulation and those treated with LAAO by sex. METHODS: Using Medicare claims data from 2015 to 2019, we identified LAAO-eligible beneficiaries and divided them into sex subgroups. Patients receiving LAAO were matched 1:1 to those receiving anticoagulation alone through propensity score matching. The risks of mortality, stroke or systemic embolism, and bleeding were compared between matched groups with adjustment for potential confounding characteristics in Cox proportional hazards models. RESULTS: Among women, 4085 LAAO recipients were matched 1:1 to those receiving anticoagulation; among men, 5378 LAAO recipients were similarly matched. LAAO was associated with a significant reduction in the risk of mortality for women and men (hazard ratio [HR], 0.509 [95% CI, 0.447-0.580]; and HR, 0.541 [95% CI, 0.487-0.601], respectively; P<0.0001), with a similar finding for stroke or systemic embolism (HR, 0.655 [95% CI, 0.555-0.772]; and HR, 0.649 [95% CI, 0.552-0.762], respectively; P<0.0001). Bleeding risk was significantly greater in LAAO recipients early after implantation but lower after the 6-week periprocedural period for women and men (HR, 0.772 [95% CI, 0.676-0.882]; and HR, 0.881 [95% CI, 0.784-0.989], respectively; P<0.05). CONCLUSIONS: In a real-world population of older Medicare beneficiaries with AF, compared with anticoagulation, LAAO was associated with a reduction in the risk of death, stroke, and long-term bleeding among women and men. These findings should be incorporated into shared decision-making with patients considering strategies for reduction in AF-related stroke.

Benefit of cardiac resynchronization therapy among older patients: A patient-level meta-analysis.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials. METHODS: Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n = 6,369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite end point of HFH or all-cause mortality or all-cause mortality alone was assessed. RESULTS: The median age was 67 years with 2436 (38%) being 70+; 1,554 (24%) were women; 2,586 (41%) had nonischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay in time to the composite end point (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66-0.85, P = .002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69-0.96, P = .017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either end point (P > .1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite end point (P for interaction = .027) with a similar but nonsignificant trend for mortality (P for interaction = .35). CONCLUSION: Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT.

IV Diuresis in Alternative Treatment Settings for the Management of Heart Failure: Implications for Mortality, Hospitalizations and Cost.

BACKGROUND: Recent advances in heart failure (HF) care have sought to shift management from inpatient to outpatient and observation settings. We evaluated the association among HF treatment in the (1) inpatient; (2) observation; (3) emergency department (ED); and (4) outpatient settings with 30-day mortality, hospitalizations and cost. METHODS: Using 100% Medicare inpatient, outpatient and Part B files from 2011-2018, 1,534,708 unique patient encounters in which intravenous (IV) diuretics were received for a primary diagnosis of HF were identified. Encounters were sorted into mutually exclusive settings: (1) inpatient; (2) observation; (3) ED; or (4) outpatient IV diuretic clinic. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 30-day hospitalization and total 30-day costs. Multivariable logistic and linear regression were used to examine the association between treatment location and the primary and secondary outcomes. RESULTS: Patients treated in observation and outpatient settings had lower 30-day mortality rates (observation OR 0.67, 95% CI 0.66-0.69; P < 0.001; outpatient OR 0.53, 95% CI 0.51-0.55; P < 0.001) compared to those treated in inpatient settings. Observation and outpatient treatment were also associated with decreased 30-day total cost compared to inpatient treatment. Observation relative cost -$5528.77, 95% CI -$5613.63 to -$5443.92; outpatient relative cost -$7005.95; 95% CI -$7103.94 to -$6907.96). Patients treated in the emergency department and discharged had increased mortality rates (OR 1.15, 95% CI 1.13-1.17; P < 0.001) and increased rates of hospitalization (OR 1.72, 95% CI 1.70-1.73; P < 0.001) compared to patients treated as inpatients. CONCLUSIONS: Medicare beneficiaries who received IV diuresis for acute HF in the outpatient and observation settings had lower mortality rates and decreased costs of care compared to patients treated as inpatients. Outpatient and observation management of acute decompensated HF, when available, is a safe and cost-effective strategy in certain populations of patients with HF.

Neurologic impact of atrial fibrillation.

PURPOSE OF REVIEW: Cognitive dysfunction is a complex condition that is becoming increasingly more prevalent. There has been growing acknowledgement that individuals with atrial fibrillation are at an increased risk of cognitive dysfunction beyond the association of age with both disorders. The purpose of this review is to explore the potential underlying mechanisms connecting atrial fibrillation and cognitive dysfunction and to examine the existing evidence for potential treatment options. RECENT FINDINGS: Many mechanisms have been proposed for the association between cognitive dysfunction and atrial fibrillation. These include cerebral infarction (both micro and macro embolic events), cerebral microbleeds including those secondary to therapeutic anticoagulation, an increased inflammatory state, cerebral hypoperfusion, and a genetic predisposition to both diseases. Treatments designed to target each of these mechanisms have led to mixed results and there are no specific interventions that have definitively led to a reduction in the incidence of cognitive dysfunction. SUMMARY: The relationship between cognitive dysfunction and atrial fibrillation remains poorly understood. Standard of care currently focuses on reducing risk factors, managing stroke risk, and maintaining sinus rhythm in appropriately selected patients. Further work needs to be conducted in this area to limit the progression of cognitive dysfunction in patients with atrial fibrillation.

Arrhythmias in Female Patients: Incidence, Presentation and Management.

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.

Arrhythmias After Acute Myocardial Infarction.

The incidence of arrhythmia after myocardial infarction has declined since the introduction of reperfusion techniques. Nevertheless, ischemic arrhythmias are often associated with increased morbidity and mortality particularly in the first 48 hours after hospital admission. This paper presents a comprehensive review of the epidemiology, characteristics, and management of ischemic tachy- and brady-arrhythmias focusing on the period shortly after myocardial infarction (MI) in patients with both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI).

Association Between Sex and Treatment Outcomes of Atrial Fibrillation Ablation Versus Drug Therapy: Results From the CABANA Trial.

BACKGROUND: Among patients with atrial fibrillation (AF), women are less likely to receive catheter ablation and may have more complications and less durable results. Most information about sex-specific differences after ablation comes from observational data. We prespecified an examination of outcomes by sex in the 2204-patient CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). METHODS: CABANA randomized patients with AF age ≥65 years or <65 years with ≥1 risk factor for stroke to a strategy of catheter ablation with pulmonary vein isolation versus drug therapy with rate/rhythm control agents. The primary composite outcome was death, disabling stroke, serious bleeding, or cardiac arrest, and key secondary outcomes included AF recurrence. RESULTS: CABANA randomized 819 (37%) women (ablation 413, drug 406) and 1385 men (ablation 695, drug 690). Compared with men, women were older (median age, 69 years versus 67 years for men), were more symptomatic (48% Canadian Cardiovascular Society AF Severity Class 3 or 4 versus 39% for men), had more symptomatic heart failure (42% with New York Heart Association Class ≥II versus 32% for men), and more often had a paroxysmal AF pattern at enrollment (50% versus 39% for men) (P<0.0001 for all). Women were less likely to have ancillary (nonpulmonary vein) ablation procedures performed during the index procedure (55.7% versus 62.2% in men, P=0.043), and complications from treatment were infrequent in both sexes. For the primary outcome, the hazard ratio for those who underwent ablation versus drug therapy was 1.01 (95% CI, 0.62-1.65) in women and 0.73 (95% CI, 0.51-1.05) in men (interaction P value=0.299). The risk of recurrent AF was significantly reduced in patients undergoing ablation compared with those receiving drug therapy regardless of sex, but the effect was greater in men (hazard ratio, 0.64 [95% CI, 0.51-0.82] for women versus hazard ratio, 0.48 [95% CI, 0.40-0.58] for men; interaction P value=0.060). CONCLUSIONS: Clinically relevant treatment-related strategy differences in the primary and secondary clinical outcomes of CABANA were not seen between men and women, and there were no sex differences in adverse events. The CABANA trial results support catheter ablation as an effective treatment strategy for both women and men. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00911508.

Comparative risk of dementia among patients with atrial fibrillation treated with catheter ablation versus anti-arrhythmic drugs.

Atrial fibrillation (AF) is associated with an increased risk of dementia. Emerging evidence suggests AF suppression is associated with reduced risk of dementia, but the optimal strategy to achieve this is unknown. We sought to compare the risk of dementia in patients with AF who underwent catheter ablation (CA) versus anti-arrhythmic drug (AAD) treatment. METHODS AND RESULTS: Using the 2000 to 2021 Optum Clinformatics database, patients with AF who underwent CA versus AAD treatment (≥1 prescription fill for ≥2 different AADs) were identified and propensity score matched overall and within sex subgroups. A cause-specific hazard model was performed to assess dementia overall and in sex-specific subgroups. After matching, there were 19,088 patients per group. CA was associated with a 41% lower risk of dementia compared with AAD alone (1.9% vs 3.3%; hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.52-0.67, log-rank P < .0001). When examined by sex, dementia risk reduction associated with CA versus AAD use alone was observed among both males (HR 0.55, 95% CI 0.46-0.66) and females (HR 0.60, 95% CI 0.50-0.72). Though not studied as a primary outcome, patients treated with CA were also observed to have 49% lower associated risk of mortality compared with AAD only (HR 0.51 95% CI 0.46-0.55, P < .0001). CONCLUSIONS: Among patients treated for AF, CA was associated with significantly lower risk of dementia and death compared with AADs only. These reductions in risk associated with CA versus AAD were seen in both males and females.

Comparative effectiveness of cardiac resynchronization therapy in older patients with heart failure: Systematic review and meta-analysis.

BACKGROUND: Pivotal CRT trials enrolled patients with HFrEF significantly younger than the typical contemporary patient with HFrEF. Thus, the risks and benefits in this older population with HFrEF are largely unknown. We sought to perform meta-analyses comparing safety and effectiveness of cardiac resynchronization therapy (CRT) in older vs younger patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: PubMed, The Cochrane Library, Scopus, and Web of Science were queried for comparative effectiveness studies of CRT in older patients with HFrEF. Title, abstract, and full-text screening was performed to identify studies comparing at least 1 prespecified end point between older and younger adult patients with at least 50 participants. Random effects meta-analysis in the left ventricular ejection fraction (LVEF) mean difference (older minus younger) and the relative risk (RR) of death, improvement in New York Heart Association (NYHA) functional class, and complications are reported along with estimates of heterogeneity. In 7 studies, there was similar LVEF improvement between groups (mean difference 1.14, 95% confidence interval [CI] -0.04 to 2.32, P = .06, I2 = 53%). Older patients were equally likely as younger patients to see an improvement in NYHA functional class of at least 1 in 6 studies (RR 0.99, 95% CI 0.93-1.06, P = .76, I2 = 25%). No significant differences in the incidence of hematoma, pneumothorax, lead dislodgment, cardiac perforation, or infection requiring explant was observed. The RR of mortality in 11 studies demonstrated higher risk of all-cause mortality in older patients (RR 1.05, 95% CI 1.03-1.08, P < .01, I2 = 0%). CONCLUSIONS: Compared with younger patients, older patients receiving CRT were equally likely to experience improvement in LVEF, left ventricular end-diastolic diameter, and NYHA functional class. There was no difference in procedural complications. The higher rate of all-cause mortality in older patients likely reflects a greater underlying risk of death from competing causes.

Efficacy and safety of dronedarone across age and sex subgroups: a post hoc analysis of the ATHENA study among patients with non-permanent atrial fibrillation/flutter.

AIMS: Age and sex may impact the efficacy of antiarrhythmic drugs on cardiovascular outcomes and arrhythmia recurrences in patients with atrial fibrillation (AF). We report on a post hoc analysis of the ATHENA study (NCT00174785), which examined cardiovascular outcomes in patients with non-permanent AF treated with dronedarone vs. placebo. METHODS AND RESULTS: Efficacy and safety of dronedarone were assessed in patients according to age and sex. Baseline characteristics were comparable across subgroups, except for cardiovascular comorbidities, which were more frequent with increasing age. Dronedarone significantly reduced the risk of cardiovascular hospitalization or death due to any cause among patients 65-74 [n = 1830; hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.60-0.83; P < 0.0001] and ≥75 (n = 1925; HR 0.75, 95% CI 0.65-0.88; P = 0.0002) years old and among males (n = 2459; HR 0.74, 95% CI 0.64-0.84; P < 0.00001) and females (n = 2169; HR 0.77, 95% CI 0.67-0.89; P = 0.0002); outcomes were similar for time to AF/AFL recurrence. Among patients aged <65 years (n = 873), cardiovascular hospitalization or death due to any cause with dronedarone vs. placebo was associated with an HR of 0.89 (95% CI 0.71-1.11; P = 0.3). The incidence of all treatment-emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation was comparable among males and females, and increased with increasing age. CONCLUSIONS: These results support the use of dronedarone for the improvement of clinical outcomes among patients aged ≥65 years and regardless of sex.

Subcutaneous and Transvenous ICDs: an Update on Contemporary Questions and Controversies.

PURPOSE OF REVIEW: While the subcutaneous (S-) implantable cardioverter-defibrillator (ICDs) is an alternative to the transvenous (TV-) ICD in many patients, optimal use remains unclear. In this review, we summarize recent clinically relevant data on sensing algorithms, inappropriate shocks, defibrillation testing, and battery and electrode failures. RECENT FINDINGS: Changes in sensing algorithms and S-ICD programming have significantly decreased inappropriate shock rates. Avoiding fat below the S-ICD coil and can is key for reducing the defibrillation threshold. While S-ICD battery and electrode failures have resulted in recalls, system components remain commercially available since failure rates are low and no other similar devices are available. The S-ICD is a good alternative to the TV-ICD for many patients, and particularly in light of recently developed device algorithms and improvements in implant technique. Future research will need to better understand: the impact of S-ICD electrode and battery failures and the potential for integrating leadless pacing into a modular S-ICD platform.

Comparative outcomes of Riata and Fidelis lead management strategies: Results from the NCDR-ICD Registry.

BACKGROUND: The Medtronic Sprint Fidelis® and Abbott Riata®/Riata ST® leads are at risk of failure and are subject to FDA recall. Comparative risks of various lead management strategies during elective generator change in a multi-center population are unknown. We aim to describe patients with functional, recalled ICD leads undergoing elective generator replacement and report outcomes according to lead management strategies. METHODS: Using data from the NCDR ICD Registry, patients with a functioning Riata® or Fidelis® lead undergoing generator replacement are described according to lead management: reuse, abandon/replace, and extract/replace. Adjusted rates of death and pre-discharge complications are reported. RESULTS: There were 13,144 generator replacement procedures involving a functioning, non-infected Riata® or Fidelis® lead (extraction n = 414, abandonment n = 427). Extraction patients were younger (mean 58 vs. 67 years) with fewer comorbidities than the reuse group. Maximum lead dwell time was similar between groups with average 94, 90, and 99 months in the extraction, abandonment, and reuse groups, respectively. In-hospital complications or mortality were more common in the extraction group (10.14%, 4.35%) compared with abandonment (1.64%, 0.47%) and reuse (0.22%, 0.07%). Compared with reuse, the adjusted odds of death or pre-discharge complication were significantly higher in the extraction group (OR 7.77 95% CI 2.42-24.95, p < .001) but not the abandonment group (OR 1.70 95% CI 0.52-5.61, p = .38). CONCLUSIONS: In this real-world population, extraction of functional recalled ICD leads was associated with significant risk of in-hospital mortality and complications. Additional work is needed to clarify whether longer term outcomes balance these peri-procedural risks.

Physicians' perceptions of shared decision-making for implantable cardioverter-defibrillators: Results of a physician survey.

BACKGROUND: Centers for Medicare and Medicaid Services has mandated the use of shared decision-making (SDM) for implantable cardioverter-defibrillator (ICD) implantation. SDM tools help facilitate quality SDM by presenting patients with balanced evidence-based facts related to risk and benefits. Perceptions of ICD implantation may differ based on patients' sex and race. OBJECTIVE: To determine if and how physicians are incorporating SDM in counseling patients about ICD and if they are aware of sex- and race-based differences in patients' perception of ICDs. METHODS: This was a pilot study involving an online survey targeting attending physicians who implant ICDs. Physicians were randomly selected by a computer-based program; 350 surveys were sent. RESULTS: Of the 124 (35%) respondents to the survey, 102 (84%) met the inclusion criteria, and of those, 99 (97%) were adult electrophysiologists. Most physicians (90, 88%) stated they engaged in SDM during the general consent process. Sixty-three (62%) physicians discuss end of life issues while obtaining general consent. Forty-four (43%) physicians said they use an existing SDM tool with the Colorado SDM tool being the most common (39, 89%). The majority of physicians were unaware of sex- and race-based differences in perceptions related to ICD implantation (sex 64, 63% and race 63, 62%). CONCLUSION: A vast majority of physicians are engaging in SDM; however less than half are using a formal SDM tool, and a minority of physicians were aware of sex- and race-based differences in patients' perception of ICD implantation. Sex- and race-based tools might help address this gap.

Outcomes Associated With Extraction Versus Capping and Abandoning Pacing and Defibrillator Leads.

BACKGROUND: Lead management is an increasingly important aspect of care in patients with cardiac implantable electronic devices; however, relatively little is known about long-term outcomes after capping and abandoning leads. METHODS: Using the 5% Medicare sample, we identified patients with de novo cardiac implantable electronic device implantations between January 1, 2000, and December 31, 2013, and with a subsequent lead addition or extraction ≥12 months after the de novo implantation. Patients who underwent extraction for infection were excluded. Using multivariable Cox proportional hazards models, we compared cumulative incidence of all-cause mortality, device-related infection, device revision, and lead extraction at 1 and 5 years for the extraction versus the cap and abandon group. RESULTS: Among 6859 patients, 1113 (16.2%) underwent extraction, whereas 5746 (83.8%) underwent capping and abandonment. Extraction patients tended to be younger (median, 78 versus 79 years; P<0.0001), were less likely to be male (65% versus 68%; P=0.05), and had shorter lead dwell time (median, 3.0 versus 4.0 years; P<0.0001) and fewer comorbidities. Over a median follow-up of 2.4 years (25th, 75th percentiles, 1.0, 4.3 years), the overall 1-year and 5-year cumulative incidence of mortality was 13.5% (95% confidence interval [CI], 12.7-14.4) and 54.3% (95% CI, 52.8-55.8), respectively. Extraction was associated with a lower risk of device infection at 5 years relative to capping (adjusted hazard ratio, 0.78; 95% CI, 0.62-0.97; P=0.027). There was no association between extraction and mortality, lead revision, or lead extraction at 5 years. CONCLUSIONS: Elective lead extraction for noninfectious indications had similar long-term survival to that for capping and abandoning leads in a Medicare population. However, extraction was associated with lower risk of device infections at 5 years.

Single vs. dual chamber implantable cardioverter-defibrillators or programming of implantable cardioverter-defibrillators in patients without a bradycardia pacing indication: systematic review and meta-analysis.

Aims: Implantable cardioverter-defibrillators (ICDs) are key in the prevention of sudden cardiac death, but outcomes may vary by type of device or programming [single chamber (SC) vs. dual chamber (DC)] in patients without a bradycardia pacing indication. We sought to meta-analyse patient outcomes of randomized trials of SC vs. DC devices or programming. Methods and results: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane trials databases for relevant studies excluding those published before 2000, involving children, or not available in English. Endpoints included mortality, inappropriate ICD therapies, and implant complications. Endpoints with at least three reporting studies were meta-analysed. We identified eight studies meeting inclusion criteria representing 2087 patients with 16.1 months mean follow-up. Mean age was 62.7 years (SD 1.92); in six studies reporting sex, most patients were male (85%). Comparing patients with a SC or DC ICD or programming, we found similar rates of mortality [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.54-1.68; P = 0.86] and inappropriate therapies (OR 1.46, 95% CI 0.97-2.19; P = 0.07) in five and six studies, respectively. In three studies of SC vs. DC ICDs (but not programming) rates of pneumothorax and lead dislodgement were not different (OR 2.12, 95% CI 0.18-24.72; P = 0.55 and OR 0.87, 95% CI 0.32-2.47; P = 0.83, respectively). Conclusion: In this meta-analysis of randomized controlled trials comparing SC vs. DC ICD device or programming, there was no significant difference in inappropriate therapies, mortality, pneumothorax, or lead dislodgement. Future studies should compare these devices over longer follow-up and in specific patient populations.

Utilization of cardiac resynchronization therapy in eligible patients hospitalized for heart failure and its association with patient outcomes.

OBJECTIVES: We examined trends in CRT utilization overall and by sex and race and to assess whether CRT use is associated with a reduction in HF hospitalization and mortality. BACKGROUND: It is unknown whether underutilization and race/sex-based differences in cardiac resynchronization therapy (CRT) use have persisted. The association between CRT and heart failure (HF) hospitalization and mortality in real-world practice remains unclear. METHODS: We linked 72,008 HF patients from 388 hospitals participating in Get With The Guidelines HF eligible for CRT with Centers for Medicare & Medicaid Services data to assess CRT utilization trends, HF hospitalization rates, and all-cause mortality. RESULTS: From 2005-2014, 18,935 (26.3%) eligible patients had CRT in place, implanted, or prescribed. The majority were male (60.0%) and white (61.9%). CRT utilization increased during the study period (P = .0002) especially in the early period. Women were less likely to receive CRT, and this difference increased over time (interaction P = .0037) despite greater mortality risk reduction (interaction P = .0043). Black patients were less likely than white patients to have CRT throughout the study period (adjusted hazard ratio (HR) 0.79; 95% CI 0.74-0.85). Patients with CRT implanted during the index hospitalization had lower mortality (adjusted HR 0.65; 95% CI 0.59-0.71) and were less likely to be readmitted for HF than patients without CRT (adjusted HR 0.64; 95% CI 0.58-0.71). CONCLUSIONS/RELEVANCE: CRT use has increased in all populations, but it remains underutilized. CRT remains more common among white than black HF patients, and women were less likely than men to receive CRT despite deriving greater benefit.

New York Heart Association class and the survival benefit from primary prevention implantable cardioverter defibrillators: A pooled analysis of 4 randomized controlled trials.

BACKGROUND: Primary prevention implantable cardioverter defibrillator (ICD) reduce all-cause mortality by reducing sudden cardiac death. There are conflicting data regarding whether patients with more advanced heart failure derive ICD benefit owing to the competing risk of nonsudden death. METHODS: We performed a patient-level meta-analysis of New York Heart Association (NYHA) class II/III heart failure patients (left ventricular ejection fraction ≤35%) from 4 primary prevention ICD trials (MADIT-I, MADIT-II, DEFINITE, SCD-HeFT). Bayesian-Weibull survival regression models were used to assess the impact of NYHA class on the relationship between ICD use and mortality. RESULTS: Of the 2,763 patients who met study criteria, 68% (n=1,867) were NYHA II and 52% (n=1,435) were randomized to an ICD. In a multivariable model including all study patients, the ICD reduced mortality (hazard ratio [HR] 0.65, 95% posterior credibility interval [PCI]) 0.40-0.99). The interaction between NYHA class and the ICD on mortality was significant (posterior probability of no interaction=.036). In models including an interaction term for the NYHA class and ICD, the ICD reduced mortality among NYHA class II patients (HR 0.55, PCI 0.35-0.85), and the point estimate suggested reduced mortality in NYHA class III patients (HR 0.76, PCI 0.48-1.24), although this was not statistically significant. CONCLUSIONS: Primary prevention ICDs reduce mortality in NYHA class II patients and trend toward reducing mortality in the heterogeneous group of NYHA class III patients. Improved risk stratification tools are required to guide patient selection and shared decision making among NYHA class III primary prevention ICD candidates.

Predicting appropriate shocks in patients with heart failure: Patient level meta-analysis from SCD-HeFT and MADIT II.

BACKGROUND: No precise tools exist to predict appropriate shocks in patients with a primary prevention ICD. We sought to identify characteristics predictive of appropriate shocks in patients with a primary prevention implantable cardioverter defibrillator (ICD). METHODS: Using patient-level data from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), we identified patients with any appropriate shock. Clinical and demographic variables were included in a logistic regression model to predict appropriate shocks. RESULTS: There were 1,463 patients randomized to an ICD, and 285 (19%) had ≥1 appropriate shock over a median follow-up of 2.59 years. Compared with patients without appropriate ICD shocks, patients who received any appropriate shock tended to have more severe heart failure. In a multiple logistic regression model, predictors of appropriate shocks included NYHA class (NYHA II vs. I: OR 1.65, 95% CI 1.07-2.55; NYHA III vs. I: OR 1.74, 95% CI 1.10-2.76), lower LVEF (per 1% change) (OR 1.04, 95% CI 1.02-1.06), absence of beta-blocker therapy (OR 1.61, 95% CI 1.23-2.12), and single chamber ICD (OR 1.67, 95% CI 1.13-2.45). CONCLUSION: In this meta-analysis of patient level data from MADIT-II and SCD-HeFT, higher NYHA class, lower LVEF, no beta-blocker therapy, and single chamber ICD (vs. dual chamber) were significant predictors of appropriate shocks.