The mechanical strength of the myocardium in patients with heart failure is primarily determined by the collagen fiber content

Background Myocardial fibrosis is a hallmark of heart failure (HF) progression, yet the direct quantitative relationship between tissue composition and passive mechanical properties in the human heart remains elusive. Current understanding relies heavily on animal models or computational simulations, failing to capture the specific biomechanical drivers of diastolic dysfunction in patients with end-stage cardiomyopathy. Purpose This study aims to bridge this critical gap by directly investigating the correlation between compositional variations (specifically fibrosis degree) and passive mechanical behaviors in human myocardial tissues. We sought to elucidate how fibrotic remodeling alters tissue stiffness and strength in end-stage disease, providing a mechanistic basis for diastolic failure that cannot be inferred from non-human models. Methods We performed a unique ex vivo biomechanical analysis on myocardial specimens obtained from 12 patients with end-stage cardiomyopathy undergoing heart transplantation. This rare human cohort enabled direct correlation analysis between histological characteristics and intrinsic passive mechanical properties, including tangent modulus (stiffness) and ultimate tensile strength, using standardized uniaxial testing protocols. Results Our analysis reveals a significant positive correlation between the degree of myocardial fibrosis and both passive stiffness (r=0.770, p=0.009) and mechanical strength (r=0.855, p=0.002) in human tissues. Notably, the association with mechanical strength was particularly pronounced (p=0.002). We identified a biomechanical paradox: while increased fibrosis enhances resistance to mechanical failure, it concurrently drives excessive stiffening that critically compromises ventricular compliance, directly impairing diastolic filling capacity. Besides, no association was found between muscle fiber volume fraction and passive mechanical properties. Conclusion This study provides the direct evidence in human hearts that fibrosis-related stiffening is a primary driver of diastolic dysfunction, highlighting the critical need for therapies that modulate myocardial composition to preserve compliance without compromising structural integrity.