A review of biomarker and imaging monitoring to predict heart failure recovery

Heart failure is a clinical syndrome caused by structural cardiac abnormalities that lead to increased intracardiac pressures and decreased cardiac output. Following cardiovascular insult or direct myocardial injury, neurohormonal activation triggers hemodynamic changes and cardiac remodeling to preserve cardiac output. While initially adaptive, cardiac remodeling eventually causes pathologic changes in cardiac structure that often compromise cardiac function. Reverse remodeling is the regression of abnormal cardiac chamber geometry and function after myocardial injury. In recent years, several classes of therapeutics have been associated with greater likelihood of reverse remodeling. Heart failure recovery and heart failure remission, terms encompassing the clinical correlates of reverse remodeling, have been associated with improved survival in patients with heart failure with reduced ejection. As such, identifying predictors of heart failure recovery can have important implications for guiding clinical practice and therapeutic innovation. This review addresses the role of biomarkers and imaging monitoring in predicting structural, functional, and clinical recovery in patients with acute and chronic heart failure

Case Report of Multiembolic Cerebrovascular Event Associated with Ramp Study Echocardiogram

The incidence of ramp test echocardiogram-associated embolic events in the setting of therapeutic anticoagulation is likely rare and has not been reported. We present such a case in a patient with a HeartMate II left ventricular assist device (LVAD) whose serial head computed tomography images, deteriorating clinical course, and the multiembolic nature of the event suggest causality. If the pretest probability of pump thrombosis in an individual LVAD patient is sufficiently high, the potential risks of performing a ramp study echocardiogram may not be warranted, even in the setting of adequate anticoagulation

Point-of-Care Technologies for Precision Cardiovascular Care and Clinical Research

Point-of-care technologies (POC or POCT) are enabling innovative cardiovascular diagnostics that promise to improve patient care across diverse clinical settings. The National Heart, Lung, and Blood Institute convened a working group to discuss POCT in cardiovascular medicine. The multidisciplinary working group, which included clinicians, scientists, engineers, device manufacturers, regulatory officials, and program staff, reviewed the state of the POCT field; discussed opportunities for POCT to improve cardiovascular care, realize the promise of precision medicine, and advance the clinical research enterprise; and identified barriers facing translation and integration of POCT with existing clinical systems. A POCT development roadmap emerged to guide multidisciplinary teams of biomarker scientists, technologists, health care providers, and clinical trialists as they: 1) formulate needs assessments; 2) define device design specifications; 3) develop component technologies and integrated systems; 4) perform iterative pilot testing; and 5) conduct rigorous prospective clinical testing to ensure that POCT solutions have substantial effects on cardiovascular care

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

Role of Apoptosis in Heart Failure

Investigators have identified biochemical and morphologic hallmarks of apoptosis in a wide variety of heart diseases; however, delineating the functional and anatomic contribution of apoptosis to the pathogenesis of heart disease has been challenging. Studies in cardiomyocytes and genetically engineered mice suggest that this contribution is likely to be substantial and may be greater than initially anticipated because of the observation that common signaling mechanisms regulate not only cardiomyocyte apoptosis but also the function of surviving cardiomyocytes. This article reviews mechanisms and implications of apoptotic signaling and evidence that these pathways contribute to cardiac dysfunction and heart failure. Consideration is given to whether these pathways represent an opportunity for therapeutic intervention

Untimely Trial Publication: A Sin of Omission?

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