New Therapeutics for Heart Failure Worsening: Focus on Vericiguat.
Patrizia RussoLaura VitielloFrancesca MilaniMaurizio VolterraniGiuseppe M C RosanoCarlo TominoStefano BonassiPublished in: Journal of clinical medicine (2024)
Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. The standard treatment of HF includes angiotensin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorticoid-receptor antagonists, beta-blockers, and sodium-glucose-co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with decreased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of reduced EF (HFrEF) therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater number of medications for the management of these patients. This review covers vericiguat's metabolism, molecular mechanisms, and drug-drug interactions.
Keyphrases
- ejection fraction
- heart failure
- nitric oxide
- left ventricular
- end stage renal disease
- aortic stenosis
- angiotensin converting enzyme
- healthcare
- newly diagnosed
- chronic kidney disease
- acute heart failure
- signaling pathway
- angiotensin ii
- cardiovascular disease
- peritoneal dialysis
- blood pressure
- emergency department
- type diabetes
- metabolic syndrome
- coronary artery disease
- small molecule
- protein kinase
- epithelial mesenchymal transition
- bone marrow
- hypertrophic cardiomyopathy
- mesenchymal stem cells
- smoking cessation
- replacement therapy
- health insurance
- sleep quality
- cardiovascular risk factors