Curtis, Lesley H.

Background Prior studies have demonstrated a link between the metabolic syndrome and increased risk of cardiovascular mortality. Whether the metabolic syndrome is associated with sudden cardiac death is uncertain. Methods and Results We characterized the relationship between sudden cardiac death and metabolic syndrome status among participants of the ARIC (Atherosclerosis Risk in Communities) Study (1987–2012) free of prevalent coronary heart disease or heart failure. Among 13 168 participants, 357 (2.7%) sudden cardiac deaths occurred during a median follow‐up of 23.6 years. Participants with the metabolic syndrome (n=4444) had a higher cumulative incidence of sudden cardiac death than those without it (n=8724) (4.1% versus 2.3%, P <0.001). After adjustment for participant demographics and clinical factors other than components of the metabolic syndrome, the metabolic syndrome was independently associated with sudden cardiac death (hazard ratio, 1.70, 95% confidence interval, 1.37–2.12, P <0.001). This relationship was not modified by sex (interaction P =0.10) or race (interaction P =0.62) and was mediated by the metabolic syndrome criteria components. The risk of sudden cardiac death varied according to the number of metabolic syndrome components (hazard ratio 1.31 per additional component of the metabolic syndrome, 95% confidence interval, 1.19–1.44, P <0.001). Of the 5 components, elevated blood pressure, impaired fasting glucose, and low high‐density lipoprotein were independently associated with sudden cardiac death. Conclusions We observed that the metabolic syndrome was associated with a significantly increased risk of sudden cardiac death irrespective of sex or race. The risk of sudden cardiac death was proportional to the number of metabolic syndrome components.

Background— QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. Methods and Results— We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0–14.4) versus 7.1% (95% CI, 6.3–8.0) and 8.2% (95% CI, 6.9–9.7) versus 4.4% (95% CI, 3.7–5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03–1.56; P =0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01–1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. Conclusions— QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.

Background— Racial and ethnic minorities are under-represented in clinical trials of primary prevention implantable cardioverter-defibrillators (ICDs). This analysis investigates the association between primary prevention ICDs and mortality among Medicare, racial/ethnic minority patients. Methods and Results— Data from Get With The Guidelines-Heart Failure Registry and National Cardiovascular Data Registry’s ICD Registry were used to perform an adjusted comparative effectiveness analysis of primary prevention ICDs in Medicare, racial/ethnic minority patients (nonwhite race or Hispanic ethnicity). Mortality data were obtained from the Medicare denominator file. The relationship of ICD with survival was compared between minority and white non-Hispanic patients. Our analysis included 852 minority patients, 426 ICD and 426 matched non-ICD patients, and 2070 white non-Hispanic patients (1035 ICD and 1035 matched non-ICD patients). Median follow-up was 3.1 years. Median age was 73 years, and median ejection fraction was 23%. Adjusted 3-year mortality rates for minority ICD and non-ICD patients were 44.9% (95% confidence interval [CI], 44.2%–45.7%) and 54.3% (95% CI, 53.4%–55.1%), respectively (adjusted hazard ratio, 0.79; 95% CI, 0.63–0.98; P =0.034). White non-Hispanic patients receiving an ICD had lower adjusted 3-year mortality rates of 47.8% (95% CI, 47.3%–48.3%) compared with 57.3% (95% CI, 56.8%–57.9%) for those with no ICD (adjusted hazard ratio, 0.75; 95% CI, 0.67%–0.83%; P <0.0001). There was no significant interaction between race/ethnicity and lower mortality risk with ICD ( P =0.70). Conclusions— Primary prevention ICDs are associated with lower mortality in nonwhite and Hispanic patients, similar to that seen in white, non-Hispanic patients. These data support a similar approach to ICD patient selection, regardless of race or ethnicity.

Background— Cardiac resynchronization therapy with defibrillator (CRT-D) reduces morbidity and mortality among selected patients with heart failure in clinical trials. The effectiveness of this therapy in clinical practice has not been well studied. Methods and Results— We compared a cohort of 4471 patients from the National Cardiovascular Data Registry’s Implantable Cardioverter-Defibrillator (ICD) Registry hospitalized primarily for heart failure and who received CRT-D between April 1, 2006, and December 31, 2009, to a historical control cohort of 4888 patients with heart failure without CRT-D from the Acute Decompensated Heart Failure National Registry (ADHERE) hospitalized between January 1, 2002, and March 31, 2006. Both registries were linked with Medicare claims to evaluate longitudinal outcomes. We included patients from the ICD Registry with left ventricular ejection fraction ≤35% and QRS duration ≥120 ms who were admitted for heart failure. We used Cox proportional hazards models to compare outcomes with and without CRT-D after adjustment for important covariates. After multivariable adjustment, CRT-D was associated with lower 3-year risks of death (hazard ratio, 0.52; 95% confidence interval, 0.48–0.56; P <0.001), all-cause readmission (hazard ratio, 0.69; 95% confidence interval, 0.65–0.73; P <0.001), and cardiovascular readmission (hazard ratio, 0.60; 95% confidence interval, 0.56–0.64; P <0.001). The association of CRT-D with mortality did not vary significantly among subgroups defined by age, sex, race, QRS duration, and optimal medical therapy. Conclusions— CRT-D was associated with lower risks of mortality, all-cause readmission, and cardiovascular readmission than medical therapy alone among patients with heart failure in community practice.

Background— Patients with heart failure and atrial fibrillation are at higher risk of thromboembolic events than patients with heart failure alone. Yet, the use of anticoagulation therapy varies in clinical practice, especially among older patients, for whom its effectiveness is poorly understood. Methods and Results— Using clinical registry data linked to Medicare claims from 2005 to 2011, we examined outcomes of older patients hospitalized with heart failure and atrial fibrillation who newly initiated anticoagulation therapy at discharge. We used Cox proportional hazards models and inverse probability-weighted treatment estimates to adjust for selection bias. Main outcomes were mortality and readmission at 1 and 3 years. Among 5105 patients in 195 hospitals, 1623 (31.8%) started anticoagulation therapy at discharge. Treated patients had lower unadjusted rates of all-cause mortality (26.4% versus 42.8%; P <0.001) and all-cause readmission (58.4% versus 63.7%; P <0.001) at 1 year. After inverse weighting for the probability of treatment and adjustment for other discharge medications, anticoagulation therapy was associated with significantly lower 1-year mortality (hazard ratio, 0.70; 99% confidence interval, 0.59–0.82), but there was no statistically significant difference in the risk of all-cause readmission (hazard ratio, 0.89; 99% confidence interval, 0.78–1.01) or other readmission outcomes. Results were similar at 3 years. Conclusions— Initiation of anticoagulation therapy at hospital discharge was associated with improved mortality at 1 and 3 years but was not associated with improved cardiovascular readmission among older patients with heart failure and atrial fibrillation.

Background— Guidelines recommend that implantable cardioverter-defibrillator (ICD) candidates have an estimated longevity of ≥1 year. Longevity can be affected by chronic kidney disease (CKD). Methods and Results— Using the National Cardiovascular Data Registry ICD registry linked with the Social Security Death Master File, we assessed the rate of death after primary prevention ICD placement between January 1, 2006, and December 31, 2007, according to CKD stage. Using Cox models, we identified factors associated with death among patients with CKD. Compared with patients without CKD (n=26 056), those with CKD (n=21 226) were older, less commonly men, more often white, and more frequently had comorbid illness. Compared with patients without CKD, patients with a glomerular filtration rate 30 to 60, glomerular filtration rate <30, and end-stage renal disease on dialysis had a higher risk of death after ICD placement (hazard ratio, 2.08; 95% confidence interval, 1.99–2.18; P <0.0001; hazard ratio, 4.20; 95% confidence interval, 3.92–4.50; P <0.0001; and hazard ratio, 4.80; 95% confidence interval, 4.46–5.17; P <0.0001, respectively). Corresponding 1-year death rates were 4.4%, 9.1%, 20.2%, and 22.4%. Among patients with CKD, factors associated with increased risk of death included CKD severity, age >65 years, heart failure symptoms, diabetes mellitus, lung disease, serum sodium <140 mEq/L, atrial fibrillation or flutter, and a lower ejection fraction. Conclusions— The risk of death after primary prevention ICD placement is proportional to CKD severity. Among patients with CKD, several factors are prognostically significant and could inform clinical decision making on primary prevention ICD candidacy.