Background
Race- and gender- specific epidemiology of incident heart failure (HF) in a contemporary elderly cohort is not well described.
Methods
We studied 2934 participants without HF enrolled in the Health ABC Study (age 73.6±2.9 years, 47.9% men, 58.6% white, 41.4% black) and assessed incidence of HF, population attributable risk (PAR) of independent risk factors for HF, and outcomes of incident HF.
Results
During a median follow-up of 7.1 years, 258 (8.8%) participants developed HF (13.6/1000 person-years). Men and blacks were more likely to develop HF. No significant sex-based differences were observed in risk factors. Coronary heart disease (whites: PAR 23.9%, blacks: PAR 29.5%) and uncontrolled blood pressure (whites: PAR 21.3%, blacks: PAR 30.1%) carried the highest PAR in both races. In blacks, 6 out of 8 risk factors assessed (coronary heart disease, uncontrolled blood pressure, left ventricular hypertrophy, reduced glomerular filtration rate, smoking, and increased heart rate) had >5% higher PAR compared to whites, leading to a higher overall proportion of HF attributable to modifiable risk factors in blacks vs. whites (67.8% vs. 48.9%). Participants who developed HF had a higher annual mortality (18.0% vs. 2.7%). No racial difference in survival after HF was noted; however, rehospitalization rates were higher in blacks (62.1 vs. 30.3/100 person-years, P<.001).
Conclusions
Incident HF is common in the elderly; a large proportion of HF risk was attributed to modifiable risk factors. Racial differences in risk factors for HF and in hospitalization rates after HF need to be accounted for prevention and treatment efforts.
BACKGROUND: Cardiovascular clinical trials depend on patient enrollment. Enrollment rates appear inadequate, but little is known about how frequently patients accept or decline offers of enrollment. The objective of this study was to assess trends and predictors of patient acceptance of offers to enroll in clinical trials for cardiovascular disease. METHODS AND RESULTS: We utilized an established database containing all randomized, controlled trials (n=1224) in cardiovascular disease published between 2001 and 2012 in the 8 highest-impact general medical and cardiology journals. Studies were eligible if the number of patients approached and number of patients declining enrollment could be ascertained from published materials. All studies were screened for eligibility. Each eligible study was reviewed by 3 co-authors. All discrepancies were resolved by the group. The main outcome was acceptance rate, defined as the number of patients enrolled divided by the number patients who were eligible and approached. Only 21.7% (n=266) of studies provided information sufficient to assess patient enrollment and refusals. The median acceptance rate across trials was 83.2%. Significant predictors of higher enrollment included: enrollment in the acute setting (P=0.031); geographical region (P<0.001 for group); and trial sponsorship (P=0.006 for group). CONCLUSIONS: Rates of reporting data sufficient to calculate acceptance rates are low. This compromises the ability to identify drivers of low enrollment and assess trial generalizability. However, the high rates of acceptance observed suggest that factors other than patients' decisions may be the primary drivers of declining rates of trial enrollment.
by
Stephen J. Greene;
Mihai Gheorghiade;
Barry A. Borlaug;
Burkert Pieske;
Muthiah Vaduganathan;
John C. Burnett;
Lothar Roessig;
Johannes‐Peter Stasch;
Scott D. Solomon;
Walter J. Paulus;
Javed Butler
by
Javed Butler;
Kevin J. Anstrom;
G. Michael Felker;
Michael M. Givertz;
Andreas Kalogeropoulos;
Marvin A. Konstam;
Douglas L. Mann;
Kenneth B. Margulies;
Steven E. McNulty;
Robert J. Mentz;
Margaret M. Redfield;
W. H. Wilson Tang;
David J. Whellan;
Monica Shah;
Patrice Desvigne-Nickens;
Adrian F. Hernandez;
Eugene Braunwald
IMPORTANCE: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. OBJECTIVE: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone. DESIGN, SETTING, AND PARTICIPANTS: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone and had NT-proBNP levels of 1000 pg/mL or more or B-type natriuretic peptide levels of 250 pg/mL or more, regardless of ejection fraction. INTERVENTIONS: High-dose spironolactone (100 mg) vs placebo or 25 mg spironolactone (usual care) daily for 96 hours MAIN OUTCOMES AND MEASURES: The primary end point was the change in NT-proBNP levels from baseline to 96 hours. Secondary end points included the clinical congestion score, dyspnea assessment, net urine output, and net weight change. Safety end points included hyperkalemia and changes in renal function. RESULTS: A total of 360 patients were randomized, of whom the median age was 65 years, 129 (36%) were women, 200 (55.5%) were white, 151 (42%) were black, 8 (2%) were Hispanic or Latino, 9 (2.5%) were of other race/ethnicity, and the median left ventricular ejection fraction was 34%. Baseline median (interquartile range) NT-proBNP levels were 4601 (2697-9596) pg/mL among the group treated with high-dose spironolactone and 3753 (1968-7633) pg/mL among the group who received usual care. There was no significant difference in the log NT-proBNP reduction between the 2 groups (−0.55 [95% CI, −0.92 to −0.18] with high-dose spironolactone and −0.49 [95% CI, −0.98 to −0.14] with usual care, P = .57). None of the secondary end point or day-30 all-cause mortality or heart failure hospitalization rate differed between the 2 groups. The changes in serum potassium and estimated glomerular filtration rate at 24, 48, 72, and 96 hours. were similar between the 2 groups. CONCLUSIONS AND RELEVANCE: Adding treatment with high-dose spironolactone to usual care for patients with AHF for 96 hours was well tolerated but did not improve the primary or secondary efficacy end points. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02235077.
Background Inotropes are widely used in hospitalized systolic heart failure (HF) patients, especially those with low systolic blood pressure (SBP) or cardiac index. In addition, inotropes are considered to be harmful in nonischemic HF. Methods and Results We examined the association of in-hospital inotrope use with (1) major events (death, ventricular assist device, or heart transplant) and (2) study days alive and out of hospital during the first 6 months in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness, which excluded patients with immediate need for inotropic therapy. Predefined subgroups of interest were baseline SBP <100 versus ≥100 mm Hg, cardiac index <1.8 vs ≥1.8 L min-1 m -2, and ischemic versus nonischemic HF etiology. Inotropes were frequently used in both the <100 mm Hg (88/165 [53.3%]) and the ≥100 mm Hg (106/262 [40.5%]) SBP subgroups and were associated with higher risk for major events in both subgroups (adjusted hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.59-5.12 [P <.001]; and HR 1.86, 95% CI 1.02-3.37 [P =.042]; respectively). Risk with inotropes was more pronounced among those with cardiac index ≥1.8 L min-1 m-2 (n = 114; HR 4.65, 95% CI 1.98-10.9; P <.001) vs <1.8 L min-1 m-2 (n = 82; HR 1.48, 95% CI 0.61-3.58; P =.39). Event rates were higher with inotropes in both ischemic (n = 215; HR 2.64, 95% CI 1.49-4.68; P =.001) and nonischemic (n = 216; HR 2.19, 95% CI 1.18-4.07; P =.012) patients. Across all subgroups, patients who received inotropes spent fewer study days alive and out of hospital. Conclusions In the absence of cardiogenic shock or end-organ hypoperfusion, inotrope use during hospitalization for HF was associated with unfavorable 6-month outcomes, regardless of admission SBP, cardiac index, or HF etiology.
Background
It is unclear whether measures of glycemic status beyond fasting glucose (FG) levels improve incident heart failure (HF) prediction in patients without history of diabetes mellitus (DM).
Methods and Results
The association of measures of glycemic status at baseline (including FG, oral glucose tolerance testing [OGTT], fasting insulin, hemoglobin A1c [HbA1c] levels, and homeostasis model assessment of insulin resistance [HOMA-IR] and insulin secretion [HOMA-B]) with incident HF, defined as hospitalization for new onset HF, was evaluated in 2386 elderly participants without history of DM enrolled in the Health ABC Study (median age 73 years; 47.6% men; 62.5% white, 37.5% black) using Cox models. After a median follow-up of 7.2 years, 185 (7.8%) participants developed HF. Incident HF rate per was 10.7 cases per 1000 person-years with FG <100mg/dL, 13.1 with FG 100–125mg/dL, and 26.6 with FG ≥126mg/dL (P=.002; P=.003 for trend). In adjusted models (for body mass index, age, history of coronary artery disease and smoking, left ventricular hypertrophy, systolic blood pressure and heart rate, and creatinine and albumin levels), FG was the strongest predictor of incident HF (adjusted HR per 10mg/dL, 1.10; 95% CI, 1.02–1.18; P=.009); the addition of OGTT, fasting insulin, HbA1c, HOMA-IR or HOMA-B did not improve HF prediction. Results were similar across race and gender. When only HF with left ventricular ejection fraction (LVEF) ≤40% was considered (n=69), FG showed a strong association in adjusted models (HR per 10mg/dL, 1.15; 95% CI, 1.03–1.29; P=.01). In comparison, when only HF with LVEF >40%, was considered (n=71), the association was weaker (HR per 10mg/dL, 1.05; 95% CI; 0.94–1.18; P=.41).
Conclusions
Fasting glucose is a strong predictor of HF risk in elderly without history of DM. Other glycemic measures provide no incremental prediction information.
by
Muhammad S Khan;
Ayman S Tahhan;
Muthiah Vaduganathan;
Stephen J Greene;
Alrohaibani Alrohaibani;
Stefan D Anker;
Orly Vardeny;
Gregg C Fonarow;
Javed Butler
Aims: The primary objective of this systematic review was to estimate the prevalence and temporal changes in chronic comorbid conditions reported in heart failure (HF) clinical trials. Methods and results: We searched MEDLINE for HF trials enrolling more than 400 patients published between 2001 and 2016.Trials were divided into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or trials enrolling regardless of ejection fraction. The prevalence of baseline chronic comorbid conditions was categorized according to the algorithm proposed by the Chronic Conditions Data Warehouse, which is used to analyse Medicare data. To test for a trend in the prevalence of comorbid conditions, linear regression models were used to evaluate temporal trends in prevalence of comorbidities. Overall, 118 clinical trials enrolling a cumulative total of 215 508 patients were included. Across all comorbidities examined, data were reported in a mean of 35% of trials, without significant improvement during the study period. Reporting of comorbidities was more common in HFrEF trials (51%) compared with HFpEF trials (27%). Among trials reporting data, hypertension (63%), ischaemic heart disease (44%), hyperlipidaemia (48%), diabetes (33%), chronic kidney disease (25%) and atrial fibrillation (25%) were the major comorbidities. The prevalence of comorbidities including hypertension, atrial fibrillation and chronic kidney disease increased over time while the prevalence of smoking decreased in HFrEF trials. Conclusion: Many HF trials do not report baseline comorbidities. A more rigorous, systematic, and standardized framework needs to be adopted for future clinical trials to ensure adequate comorbidity reporting and improve recruitment of multi-morbid HF patients.
As a result of the improved survival of patients with heart failure (HF) and the overall rise in the prevalence of HF,1 the number of patients in advanced (stage D) HF continues to increase, thus exceeding the limited availability of donor organs by a wide margin.2 Initially used primarily as a bridge to heart transplantation, mechanical circulatory support is now increasingly offered as a destination therapy to patients with advanced HF in clinical deterioration who are not candidates for transplantation. Improvement in survival to 80% at 1-year postimplantation3 has steadily followed the development of new technologies such as the continuous-flow pump, which now encompasses 99% of left ventricular assist devices (LVADs),3 and improvements in patient and device management. Far from being a panacea, mechanical circulatory support is still fraught with challenges. Among them, post-LVAD right ventricular failure (RVF) is a major cause of morbidity and mortality.