Background: The Fibrosis Paradox in Heart Failure
Heart failure remains a global epidemic, affecting over 64 million people worldwide and carrying a five-year mortality rate that rivals many malignancies. While significant advances have been made in pharmacological and device-based therapies, a substantial proportion of patients continue to experience progressive deterioration despite optimal medical management. This clinical reality has prompted researchers to look beyond conventional hemodynamic parameters and explore the underlying biological drivers of adverse cardiac remodeling.
At the cellular level, myocardial fibrosis represents one of the most critical pathobiological processes contributing to heart failure progression. Activated cardiac fibroblasts play a central role in this process, depositing extracellular matrix proteins and contributing to ventricular stiffness, diastolic dysfunction, and arrhythmogenesis. However, the extent and pattern of fibroblast activation vary considerably between patients, particularly when comparing ischemic cardiomyopathy (ICM) resulting from myocardial infarction to nonischemic cardiomyopathy (NICM) with diverse etiologies such as inflammatory, toxic, or idiopathic causes.
