Hernandez, Adrian

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— Exercise intolerance is a hallmark of heart failure, but factors associated with impaired exercise capacity in heart failure with preserved ejection fraction are unclear. We hypothesized that in heart failure with preserved ejection fraction, the severity of resting ventricular and vascular dysfunction are associated with impairment in exercise tolerance as assessed by peak oxygen consumption. Methods and Results— Subjects with heart failure with preserved ejection fraction enrolled in the PhosphodiesteRasE-5 Inhibition to Improve CLinical Status And EXercise Capacity in Diastolic Heart Failure (RELAX) clinical trial (n=216) underwent baseline Doppler echocardiography, cardiopulmonary exercise testing, and cardiac MRI. RELAX participants were elderly (median age 69 years) and 48% were women. Ejection fraction (60%) and stroke volume (77 mL) were normal, while diastolic dysfunction (medial E / e ′, 16; deceleration time, 185 ms; left atrial volume, 44 mL/m 2 ) and increased arterial load (arterial elastance, 1.51 mm Hg/mL) were evident. Peak oxygen consumption was reduced (11.7 mLkg −1 min −1 , 1141 mL/min) and age, sex, body mass index, hemoglobin, and chronotropic response collectively explained 64% of the variance in raw peak oxygen consumption (mL/min). After adjustment for these variables, left ventricular structure (diastolic dimension [1.5%, P =0.008] and left ventricular mass [1.6%, P =0.008]), resting stroke volume (2.0%, P =0.002), left ventricular diastolic dysfunction (deceleration time [0.9%, P =0.03] and E / e ′ [1.4%, P =0.009]), and arterial function (arterial elastance [2.1%, P =0.002] and systemic arterial compliance [1.5%, P =0.007]), each explained only a small additional portion of the variance in peak oxygen consumption. Conclusions— In heart failure with preserved ejection fraction, potentially modifiable factors (obesity, anemia, and chronotropic incompetence) are strongly associated with exercise capacity, whereas resting measures of ventricular and vascular structure and function are not. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00763867

Background— Atrial fibrillation (AF) is common among patients with heart failure and preserved ejection fraction (HFpEF), but its clinical profile and impact on exercise capacity remain unclear. RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized trial testing the impact of sildenafil on peak V O 2 in stable outpatients with chronic HFpEF. We sought to compare clinical features and exercise capacity among patients with HFpEF who were in sinus rhythm (SR) or AF. Methods and Results— RELAX enrolled 216 patients with HFpEF, of whom 79 (37%) were in AF, 124 (57%) in SR, and 13 in other rhythms. Participants underwent baseline cardiopulmonary exercise testing, echocardiogram, biomarker assessment, and rhythm status assessment before randomization. Patients with AF were older than those in SR but had similar symptom severity, comorbidities, and renal function. β-blocker use and chronotropic indices were also similar. Despite comparable left ventricular size and mass, AF was associated with worse systolic (lower EF, stroke volume, and cardiac index) and diastolic (shorter deceleration time and larger left atria) function compared with SR. Pulmonary artery systolic pressure was higher in AF. Patients with AF had higher N-terminal pro-B-type natriuretic peptide, aldosterone, endothelin-1, troponin I, and C-telopeptide for type I collagen levels, suggesting more severe neurohumoral activation, myocyte necrosis, and fibrosis. Peak V O 2 was lower in AF, even after adjustment for age, sex, and chronotropic response, and V E /V CO 2 was higher. Conclusions— AF identifies an HFpEF cohort with more advanced disease and significantly reduced exercise capacity. These data suggest that evaluation of the impact of different rate or rhythm control strategies on exercise tolerance in patients with HFpEF and AF is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00763867.

Background— Congestion is a primary driver of symptoms in patients with acute heart failure, and relief of congestion is a critical goal of therapy. Monitoring of response to therapy through the assessment of daily weights and net fluid loss is the current standard of care, yet the relationship between commonly used markers of decongestion and both patient reported symptom relief and clinical outcomes are unknown. Methods and Results— We performed a retrospective analysis of the randomized clinical trial, Diuretic Optimization Strategy Evaluation in Acute Heart Failure (DOSE-AHF), enrolling patients hospitalized with a diagnosis of acute decompensated heart failure. We assessed the relationship among 3 markers of decongestion at 72 hours—weight loss, net fluid loss, and percent reduction in serum N terminal B-type natriuretic peptide (NT-proBNP) level—and relief of symptoms as defined by the dyspnea visual analog scale area under the curve. We also determined the relationship between each marker of decongestion and 60-day clinical outcomes defined as time to death, first rehospitalization or emergency department visit. Mean age was 66 years, mean ejection fraction was 35%, and 27% had ejection fraction ≥50%. Of the 3 measures of decongestion assessed, only percent reduction in NT-proBNP was significantly associated with symptom relief ( r =0.13; P =0.04). There was no correlation between either weight loss or net fluid loss and symptom relief, ( r =0.04; P =0.54 and r =0.07; P =0.27, respectively). Favorable changes in each of the 3 markers of decongestion were associated with improvement in time to death, rehospitalization, or emergency department visit at 60 days (weight: hazard ratio, 0.91; 95% confidence interval, 0.85–0.97 per 4 lbs; weight lost; fluid hazard ratio, 0.94; 95% confidence interval, 0.90–0.99 per 1000 mL fluid loss; NT-proBNP hazard ratio, 0.95; 95% confidence interval, 0.91–0.99 per 10% reduction). These associations were unchanged after multivariable adjustment with the exception that percent reduction in NT-proBNP was no longer a significant predictor (hazard ratio, 0.97; 95% confidence interval, 0.93–1.02). The rates of death, HF hospitalization, or emergency department visit at 60 days for patients with 0, 1, 2, and 3 markers of decongestion (above the median) were 67%, 64%, 46%, and 38%, respectively (log rank P value=0.05). Figure. Relationship between number of markers of decongestion above median* and time to 60-day risk of emergency department (ED) visit, rehospitalization, or death. *Median net fluid loss, 3.8 L; median net weight loss, 6.5 lbs; median percent reduction in N terminal B-type natriuretic peptide 24.3%. Conclusions— Weight loss, fluid loss, and NT-proBNP reduction at 72 hours are poorly correlated with dyspnea relief. However, favorable improvements in each of the 3 markers were associated with improved clinical outcomes at 60 days. These data suggest the need for ongoing research to understand the relationships among symptom relief, congestion, and outcomes in patients with acute decompensated heart failure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00577135.

Background— Prior studies have demonstrated low use of implantable cardioverter defibrillators (ICDs) as primary prevention, particularly among women and blacks. The degree to which the overall use of ICD therapy and disparities in use have changed is unclear. Methods and Results— We examined 11 880 unique patients with a history of heart failure and left ventricular ejection fraction ≤35% who were ≥65 years old and enrolled in the Get With the Guidelines–Heart Failure (GWTG-HF) program from January 2005 through December 2009. We determined the rate of ICD use by year for the overall population and for sex and race groups. From 2005 to 2007, overall ICD use increased from 30.2% to 42.4% and then remained unchanged in 2008 to 2009. After adjustment for potential confounders, ICD use increased significantly in the overall study population during 2005 to 2007 (odds ratio, 1.28; 95% confidence interval, 1.11–1.48 per year; P =0.0008) and in black women (odds ratio, 1.82; 95% confidence interval, 1.28–2.58 per year; P =0.0008), white women (odds ratio, 1.30; 95% confidence interval, 1.06–1.59 per year; P =0.010), black men (odds ratio, 1.54; 95% confidence interval, 1.19–1.99 per year; P =0.0009), and white men (odds ratio, 1.25; 95% confidence interval, 1.06–1.48 per year; P =0.0072). The increase in ICD use was greatest among blacks. Conclusions— In the GWTG-HF quality improvement program, a significant increase in ICD therapy use was observed over time in all sex and race groups. The previously described racial disparities in ICD use were no longer present by the end of the study period; however, sex differences persisted.