Key result
Fibrosis and microvascular ischemia drive sudden cardiac death risk and electrical instability in HCM.
Why the study?
The biological determinants of ventricular arrhythmic vulnerability leading to sudden cardiac death in hypertrophic cardiomyopathy remain incompletely defined.
Systematic Review
Fibro-inflammatory signaling, fibrotic remodeling, and microvascular ischemia appear to converge as an integrated mechanism-to-substrate model for sudden cardiac death vulnerability in hypertrophic cardiomyopathy.
Integrate fibrosis assessment into HCM SCD risk stratification; extends substrate models to include microvascular ischemia and fibro-inflammatory pathways.
Hypertrophic cardiomyopathy (HCM) remains an important cause of sudden cardiac death (SCD), but the biological determinants of ventricular arrhythmic vulnerability remain incompletely defined. This systematic translational review examined whether fibro-inflammatory signaling, fibrotic remodeling, and microvascular ischemia represent convergent components of the arrhythmogenic substrate in HCM. MEDLINE/PubMed, Embase, Web of Science Core Collection, and Cochrane Library were searched from inception to January 2026. Of 167 records, 37 full-text reports were assessed and 11 studies included. Fibrosis emerged as the most clinically mature substrate marker, while microvascular ischemia appeared to amplify electrical instability, particularly in remodeled myocardium. Molecular and tissue studies suggested upstream fibro-inflammatory programs involving activated fibroblasts, extracellular matrix dysregulation, SMAD/TGF-beta signaling, CRLF1/LIFR-JAK-STAT signaling, and altered multicellular communication. Overall, the evidence supports an integrated mechanism-to-substrate model, but prospective outcome-validated studies are needed before these biological layers can refine SCD risk stratification beyond established clinical and imaging markers in contemporary HCM practice.
No takes yet. Share an insight, caveat, or question.
Menezes et al. (2026) conducted a systematic review in Hypertrophic cardiomyopathy (HCM). Fibro-inflammatory signaling, fibrotic remodeling, and microvascular ischemia was evaluated on Ventricular arrhythmic vulnerability and sudden cardiac death (SCD) susceptibility. Fibrosis emerged as the most clinically mature substrate marker for sudden cardiac death, while microvascular ischemia amplified electrical instability in remodeled myocardium in hypertrophic cardiomyopathy.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: