SGLT2 Inhibitors in Hypertrophic Cardiomyopathy: Emerging Evidence and Putative Mechanisms.

Area of Science:

• Cardiology
• Molecular Medicine
• Metabolic Disorders

Background:

• Hypertrophic cardiomyopathy (HCM) is a primary inherited heart muscle disease linked to heart failure and sudden cardiac death.
• While genetic mutations initiate HCM, oxidative stress, mitochondrial dysfunction, and nutrient signaling significantly drive its progression.
• Reactive oxygen species (ROS) exacerbate HCM by impairing energy production, calcium handling, and promoting fibrosis.

Purpose of the Study:

• To review the molecular mechanisms linking oxidative stress and hypertrophic remodeling in HCM.
• To explore the potential of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as a disease-modifying therapy for HCM.

Main Methods:

• Literature review of preclinical and translational studies on HCM.
• Analysis of the role of oxidative stress and mitochondrial dysfunction in HCM pathogenesis.
• Evaluation of the therapeutic mechanisms of SGLT2 inhibitors in cardiovascular disease.

Main Results:

• SGLT2 inhibitors demonstrate cardioprotective effects in heart failure, independent of glucose control.
• SGLT2i improve myocardial metabolism, reduce oxidative stress, and enhance mitochondrial function.
• Preclinical data suggest SGLT2i may counteract key pathophysiological processes in HCM.

Conclusions:

• Oxidative stress and mitochondrial dysfunction are critical in HCM progression.
• SGLT2 inhibitors possess pleiotropic effects that may counteract HCM pathophysiology.
• Targeting these mechanisms with SGLT2 inhibitors represents a potential disease-modifying strategy for HCM.