Omecamtiv mecarbil in Black patients with heart failure and reduced ejection fraction: insights from GALACTIC-HF

Background: Omecamtiv mecarbil improves cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Consistency of drug benefit across race is a key public health topic. Objectives: The purpose of this study was to evaluate the effect of omecamtiv mecarbil among self-identified Black patients. Methods: In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patients with symptomatic HF, elevated natriuretic peptides, and left ventricular ejection fraction (LVEF) ≤35% were randomized to omecamtiv mecarbil or placebo. The primary outcome was a composite of time to first event of HF or cardiovascular death. The authors analyzed treatment effects in Black vs White patients in countries contributing at least 10 Black participants. Results: Black patients accounted for 6.8% (n = 562) of overall enrollment and 29% of U.S. enrollment. Most Black patients enrolled in the United States, South Africa, and Brazil (n = 535, 95%). Compared with White patients enrolled from these countries (n = 1,129), Black patients differed in demographics, comorbid conditions, received higher rates of medical therapy and lower rates of device therapies, and experienced higher overall event rates. The effect of omecamtiv mecarbil was consistent in Black vs White patients, with no difference in the primary endpoint (HR = 0.83 vs 0.88, P-interaction = 0.66), similar improvements in heart rate and N-terminal pro–B-type natriuretic peptide, and no significant safety signals. Among endpoints, the only nominally significant treatment-by-race interaction was the placebo-corrected change in blood pressure from baseline in Black vs White patients (+3.4 vs −0.7 mm Hg, P-interaction = 0.02). Conclusions: GALACTIC-HF enrolled more Black patients than other recent HF trials. Black patients treated with omecamtiv mecarbil had similar benefit and safety compared with White counterparts

Quantitative Electrocardiographic Measures and Long-Term Mortality in Exercise Test Patients With Clinically Normal Resting Electrocardiograms

BACKGROUND: Currently the only function of the resting electrocardiogram (ECG) in patients referred for exercise testing is to determine whether imaging is mandated. It is unknown if subtle ECG findings in those patients with clinically normal resting ECGs have prognostic significance. METHODS: We performed a single-center cohort study of 18,964 patients without known CVD, who had a clinically normal resting ECG and who underwent treadmill exercise testing for evaluation of suspected CAD. Eleven quantitative ECG measures related to heart rate, conduction, left ventricular mass, or repolarization were collected digitally. The primary outcome was all-cause mortality. The prognostic importance of a composite ECG score was assessed by measuring its impact on the c-index (analogous to area under ROC curve), and by measures of reclassification. RESULTS: During a median follow-up of 10.7 years 1,585 patients died. The four most predictive digital ECG variables were higher ventricular rate, more left-ward QRS axis, and more downward ST segment deviation, and longer QT interval. The ECG score was independently associated with mortality (75(th) vs. 25(th) percentile HR 1.36, 95% CI [1.25 to 1.49], P<.0001). The ECG score had modest impact on discrimination (change in c-index 0.04) and reclassification of risk (3.0% decrease of relative integrated discrimination improvement, P<.001). CONCLUSIONS: Subtle ECG findings relating to heart rate, conduction, left ventricular mass, or repolarization in patients with clinically normal ECGs referred for exercise testing may provide modest additional prognostic information over and above clinical and exercise measures

Cardiac resynchronization therapy-heart failure (CRT-HF) clinic: A novel model of care.

BackgroundPost-implant care of patients with heart failure (HF) undergoing cardiac resynchronization therapy (CRT) is not addressed in current HF or CRT guidelines and is often fragmented with poor communication between specialties. We sought to develop a new model of post-CRT care which could be implemented in busy clinical settings.Methods and resultsWe designed a novel, multidisciplinary approach to standardizing post CRT care. All patients receiving a CRT device at the Cleveland Clinic between March 2017 and August 2018 were invited to be seen in the clinic 6 months post implant. A one-time collaborative visit encompassing cardiac imaging, heart failure, and electrophysiology care was performed. We recorded the operational feasibility of the clinic in terms of patient throughput as well as patient characteristics, interventions, and new diagnoses made. Between September 2017 and February 2019, 150 patients were seen in the clinic. Of these, 125 patients had their index CRT implanted for standard indications and were included in the current analysis. Approximately 45 minutes were dedicated for each patient visit. Interventions in care were made in 95% of patients, with CRT non-responders offered a higher number of interventions as compared to responders (median 3 versus 2 interventions). Types of interventions were device-related (26% of population), medication-related (74%), and referral for alternate medical services (80%).ConclusionsMultidisciplinary post-implant care of patients with HF receiving CRT devices, regardless of CRT response status, is feasible and results in frequent medical interventions

Importance of Treadmill Exercise Time as an Initial Prognostic Screening Tool in Patients With Systolic Left Ventricular Dysfunction

BACKGROUND: We sought to determine if treadmill exercise time may be of value as an initial prognostic screening tool in ambulatory patients with impaired systolic function referred for cardiopulmonary exercise testing. METHODS AND RESULTS: We studied 2,231 adult systolic heart failure patients (27% women) who underwent cardiopulmonary stress testing using a modified Naughton protocol. We assessed the value of treadmill exercise time for prediction of all-cause death and a composite of death or UNOS status 1 heart transplantation. During a mean follow up of 5 years, 742 (33%) patients died. There were 249 (11%) UNOS status 1 heart transplants. Treadmill exercise time was predictive of death and the composite outcome in both women and men, even after accounting for peak oxygen consumption and other clinical covariates (adjusted hazard ratio of lowest versus high sex-specific quartile for prediction of death 1.70, 95% CI 1.05–2.75, P=0.03, and for prediction of the composite outcome 1.75, 95% CI 1.15–2.66, P=0.009). For a one minute change in exercise time there was a 7% increased hazard of death (e.g. comparing 480 to 540 seconds HR 1.07, 95% CI 1.02–1.12, P=0.004). CONCLUSIONS: Since cardiopulmonary stress testing is not available in every hospital, treadmill exercise time using a modified Naughton protocol may be of value as an initial prognostic screening tool