New medical therapies for heart failure

Abstract

Heart failure (HF) can rightfully be called the epidemic of the 21(st) century. Historically, the only available medical treatment options for HF have been diuretics and digoxin, but the capacity of these agents to alter outcomes has been brought into question by the scrutiny of modern clinical trials. In the past 4 decades, neurohormonal blockers have been introduced into clinical practice, leading to marked reductions in morbidity and mortality in chronic HF with reduced left ventricular ejection fraction (LVEF). Despite these major advances in pharmacotherapy, our understanding of the underlying disease mechanisms of HF from epidemiological, clinical, pathophysiological, molecular, and genetic standpoints remains incomplete. This knowledge gap is particularly evident with respect to acute decompensated HF and HF with normal (preserved) LVEF. For these clinical phenotypes, no drug has been shown to reduce long-term clinical event rates substantially. Ongoing developments in the pharmacotherapy of HF are likely to challenge our current best-practice algorithms. Novel agents for HF therapy include dual-acting neurohormonal modulators, contractility-enhancing agents, vasoactive and anti-inflammatory peptides, and myocardial protectants. These novel compounds have the potential to enhance our armamentarium of HF therapeutics.

Mechanisms of action of sacubitril/valsartan on cardiac remodeling: a systems biology approach

“…Indeed, it has recently been reported that Sacubitril/Valsartan has the potential to lower high-sensitivity troponin T (hs-TnT) levels, a biomarker for myocyte injury and myocardial cell death, in HF patients. 29, 30 Taking this into account, our analyses now provide a new perspective on relevant, though previously unknown, MoA.…”

From Bench to Bedside: New Approaches to Therapeutic Discovery for Heart Failure

“…Potential pharmacological agents have been identified that target pathophysiological features of the failing heart. Many new medical therapies of heart failure have been extensively reviewed elsewhere (see [15, 16]). Here we focus on two recent therapies that have had positive results from phase II and/or phase III clinical trials.…”

Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction

“…Contrary to expectations, recent clinical studies have failed to demonstrate the benefits offered by drugs effective in HFrEF to HFpEF patients (16, 21–23). Thus, HFpEF is one of the largest unmet needs in cardiovascular medicine, and there is a substantial requirement for new therapeutic approaches and strategies that target mechanisms specific for HFpEF (16).…”