Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Clinical correlates of hand-held ultrasound-guided assessments of the inferior vena cava in patients with acute decompensated heart failure.

BACKGROUND: Accurately assessing volume status in acutely decompensated heart failure (ADHF) can be challenging. Inferior vena cava (IVC) dynamics by echocardiography allow indirect assessment of volume status in these patients. Recently introduced hand-held ultrasound devices are promising. We aimed to describe the clinical correlates of volume status assessment using a hand-held ultrasound device in ADHF. METHODS: In this prospective study, we evaluated 106 patients admitted with ADHF. First scan was performed within 24 hours of admission and timed in reference to first dose of intravenous diuretic. Daily resting and inspiratory (sniff) IVC diameters were measured according to standard echocardiography methods during hospitalization including the day of discharge. IVC collapsibility index (IVC-CI = Maximum IVC diameter-Inspiratory IVC diameter/maximum diameter; RESULTS: Data for 106 patients was analyzed. Mean age was 66.7 ± 13.8 years, of which 53.8% were females, and a mean ejection fraction was 39 ± 18%. Initial scan of the IVC was obtained at an average time of 5.2 ± 8.04 hours from first diuretic dose. 81.2% of patients at admission had an IVC-CI CONCLUSION: Hand-held ultrasound assessment of IVC-CI in ADHF patients, although a feasible concept, is unable to predict 30-day readmissions in our study. Further prospective studies are necessary

Marital status and living condition as predictors of mortality and readmissions among African Americans with heart failure.

UNLABELLED: Socioeconomic factors, including social support, may partially explain why African Americans (AA) have the highest prevalence of heart failure and with worse outcomes compared to other races. AA are more likely to be hospitalized and readmitted for heart failure and have higher mortality. The purpose of this study is to determine whether the social factors of marital status and living condition affect readmission rates and all-cause mortality following hospitalization for acute decompensated heart failure (ADHF) in AA patients. METHODS: Medical records from 611 AA admitted to Einstein Medical Center Philadelphia from January, 2011 to February, 2013 for ADHF were reviewed. Patient demographics including living condition (nursing home residents, living with family or living alone) and marital status (married or non-married -including single, divorced, separated and widowed) were correlated with all-cause mortality and readmission rates. RESULTS: In this cohort (53% male, mean age 65±15, mean ejection fraction 32±16%) 25% (n=152) of subjects were unmarried. Unmarried patients had significantly higher 30-day readmission rates (16% vs. 6% p=0.0002) and higher 1-year mortality (17% vs. 11% p=0.047) compared with married patients. Fifty percent (n=303) of subjects were living with family members, while 40% (n=242) and 11% (n=66) were living alone or in a nursing facility, respectively. Patients living with family members had significantly lower 30-day readmission rates when compared with those living alone or in a nursing facility (7% vs 21% vs. 18% p= CONCLUSION: The socioeconomic factors of marital status and living condition significantly correlated with mortality and 30-day readmission rate in AA heart failure patients. Specifically, being married and living with family independently predict lower mortality and fewer readmissions. Surprisingly, living in a nursing facility was associated with significantly higher mortality than living alone or with family

Etiologies and predictors of readmission among obese and morbidly obese patients admitted with heart failure

The relationship between severity of obesity and outcomes in heart failure (HF) has long been under debate. We studied index HF admissions from the 2013-14 National Readmission Database. Admissions were separated into three weight-based categories: non-obese (Non-Ob), obese (Ob), and morbidly obese (Morbid-Ob) to analyze hospital mortality and readmission at 30 days and 6 months. We investigated etiologies and predictors of 30-day readmission among these weight categories. We studied a total of 578,213 patients of whom 3.0% died during index hospitalization (Non-Ob 3.3% vs. Ob 1.9% vs. Morbid-Ob 1.9%; p \u3c 0.01). Non-Ob comprised 79.5%, Ob 9.9%, and Morbid-Ob 10.6% of patients. Morbid-Ob patients were the youngest among age categories and more likely to be female. In-hospital mortality during readmission at 30 days and 6 months was significantly lower among Morbid-Ob and Ob compared with Non-Ob patients (all p \u3c 0.01). Thirty-day readmission among Morbid-Ob was lower than Non-Ob and higher than Ob patients (19.6% vs. 20.5% vs. 18.6%, respectively; p \u3c 0.01). Morbid-Ob patients were less likely to be readmitted for cardiovascular etiologies compared with both Ob and Non-Ob (45.0% vs. 50.3% vs. 50.6%; p \u3c 0.01). Multivariable regression analysis revealed that Ob (adjusted odds ratio 0.84, 95% confidence intervals 0.82-0.86) and Morbid-Ob (aOR 0.83, 95% CI 0.81-0.85) were independently associated with lower 30-day readmission. Readmission at 6 months was highest among Morbid-Ob followed by Non-Ob and Ob (51.1% vs. 50.2% vs. 49.1%, p \u3c 0.01). Morbid-Ob and Ob patients experience lower in-hospital mortality during index HF admission and during readmission with 30 days or 6 months compared with Non-Ob. Morbid-Ob patients experience greater readmission at 6 months despite the lower rate at 30 days post discharge. Morbid-Ob patients are most likely to be readmitted for non-cardiovascular causes

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)