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

Comparison of Cardiac Reverse Remodeling between Older and Newer Generation Continuous-Flow LVAD

Purpose: The purpose of our study is to compare the left ventricular (LV) functional and structural changes following mechanical circulatory support (MCS) between continuous-flow left ventricular assist devices (CF-LVADs) that provide mechanical unloading characterized by specific bioengineering differences. Methods: The study enrolled 311 chronic HF patients undergoing MCS with HVAD (HW, hybrid levitation centrifugal pump, n=95), HeartMate 3 (HM3, full magnetic levitation centrifugal pump, n=140), and HeartMate II (HM2, axial flow pump, n=76) at four sites across the US. Echocardiographic parameters of LV structure and function were obtained pre-implant and at 1, 3, 6, and 12 months of CF-LVAD support. Results: There were no significant differences in baseline characteristics between groups. At 3 months post-LVAD support the LV ejection fraction (LVEF) was higher (p=0.03, Figure 1A) and left ventricular end diastolic diameter (LVEDD) was lower (p=0.04, Figure 1B) in HMII patients, but there were no significant difference in LVEF and LVEDD between devices at 6 or 12 months. The proportion of patients achieving “cardiac reverse remodeling responder” status (defined as improvement of LVEF to ≥40% and LVEDD \u3c6.0cm) was 9.32%, and comparable between the CF-LVADs. Conclusion: The newest generation full magnetically levitated CF-LVAD results in similar cardiac reverse remodeling as older generation CF-LVADs. These findings suggest that the fully magnetically levitated device technology could provide an adequate platform to further study and promote reverse cardiac remodeling clinically

Repeated Measurement of the Intermountain Risk Score Enhances Prognostication for Mortality

<div><p>Background</p><p>The Intermountain Risk Score (IMRS), composed of the complete blood count (CBC) and basic metabolic profile (BMP), predicts mortality and morbidity in medical and general populations. Whether longitudinal repeated measurement of IMRS is useful for prognostication is an important question for its clinical applicability.</p><p>Methods</p><p>Females (N = 5,698) and males (N = 5,437) with CBC and BMP panels measured 6 months to 2.0 years apart (mean 1.0 year) had baseline and follow-up IMRS computed. Survival analysis during 4.0±2.5 years (maximum 10 years) evaluated mortality (females: n = 1,255 deaths; males: n = 1,164 deaths) and incident major events (myocardial infarction, heart failure [HF], and stroke).</p><p>Results</p><p>Both baseline and follow-up IMRS (categorized as high-risk vs. low-risk) were independently associated with mortality (all p<0.001) in bivariable models. For females, follow-up IMRS had hazard ratio (HR) = 5.23 (95% confidence interval [CI] = 4.11, 6.64) and baseline IMRS had HR = 3.66 (CI = 2.94, 4.55). Among males, follow-up IMRS had HR = 4.28 (CI = 3.51, 5.22) and baseline IMRS had HR = 2.32 (CI = 1.91, 2.82). IMRS components such as RDW, measured at both time points, also predicted mortality. Baseline and follow-up IMRS strongly predicted incident HF in both genders.</p><p>Conclusions</p><p>Repeated measurement of IMRS at baseline and at about one year of follow-up were independently prognostic for mortality and incident HF among initially hospitalized patients. RDW and other CBC and BMP values were also predictive of outcomes. Further research should evaluate the utility of IMRS as a tool for clinical risk adjustment.</p></div

Association of follow-up IMRS and baseline IMRS, modeled as continuous variables, with mortality in Cox regression.

*<p>Adjusted for baseline IMRS;</p>†<p>Adjusted for follow-up IMRS. CI: confidence interval.</p