Key result
Heart failure pharmacotherapy shifts from neurohormonal antagonism to direct cardiac targets including SGLT2 inhibitors.
Why the study?
To review current and novel therapeutic strategies in chronic heart failure from a pathophysiological perspective.
The therapeutic landscape for heart failure is expanding beyond traditional neurohormonal blockade to include novel targets addressing myocardial contractility, metabolism, and cellular signaling.
May inform contemporary heart failure prescribing patterns; leaves open comparative trials of direct cardiac targets.
After initial strategies targeting inotropism and congestion, the neurohormonal interpretative model of heart failure (HF) pathophysiology has set the basis for current pharmacological management of HF, as most of guideline recommended drug classes, including beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists, blunt the activation of detrimental neurohormonal axes, namely sympathetic and renin-angiotensin-aldosterone (RAAS) systems. More recently, sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, combining inhibition of RAAS and potentiation of the counter-regulatory natriuretic peptide system, has been consistently demonstrated to reduce mortality and HF-related hospitalization. A number of novel pharmacological approaches have been tested during the latest years, leading to mixed results. Among them, drugs acting directly at a second messenger level, such as the soluble guanylate cyclase stimulator vericiguat, or other addressing myocardial energetics and mitochondrial function, such as elamipretide or omecamtiv-mecarbil, will likely change the therapeutic management of patients with HF. Sodium glucose cotransporter 2 inhibitors, initially designed for the management of type 2 diabetes mellitus, have been recently demonstrated to improve outcome in HF, although mechanisms of their action on cardiovascular system are yet to be elucidated. Most of these emerging approaches have shifted the therapeutic target from neurohormonal systems to the heart, by improving cardiac contractility, metabolism, fibrosis, inflammation, and remodeling. In the present paper, we review from a pathophysiological perspective current and novel therapeutic strategies in chronic HF.
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Ghionzoli et al. (2021) conducted a review in Heart failure. Current and emerging heart failure therapies was evaluated. Recent advancements in heart failure pharmacotherapy have shifted the therapeutic focus from neurohormonal antagonism to direct cardiac targets, including SGLT2 inhibitors and myosin motor activators.
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