Passive and Viscoelastic Myocardial Stiffness Across Scales: Measurement, Modelling, Imaging, and Clinical Translation

Myocardial stiffness is a critical determinant of cardiac function and disease, influencing ventricular filling, contractility, mechanotransduction, and the progression of conditions such as hypertrophic cardiomyopathy, myocardial infarction, and heart failure with preserved ejection fraction. Over the past two decades, research in cardiac biomechanics has advanced from conventional ex vivo tissue characterization to multiscale experimental investigation, sophisticated constitutive modelling, and patient-specific computational inference based on imaging modalities such as magnetic resonance imaging and echocardiography.Despite these advances, the field remains fragmented across experimental biomechanics, computational modelling, and clinical imaging. Experimental studies commonly focus on isolated tissue characterization using biaxial testing, indentation, and rheological methods, whereas computational studies increasingly employ inverse finite element frameworks to estimate myocardial stiffness in vivo. At the same time, growing evidence indicates that myocardial viscoelasticity and other time-dependent mechanical behaviours play an important role in cardiac function, although these features are still insufficiently incorporated into many constitutive models.This review synthesises current knowledge on passive and viscoelastic myocardial stiffness across scales by integrating experimental methods, constitutive modelling strategies, and image-informed computational approaches. It examines the influence of myocardial microstructure, fibre architecture, extracellular matrix remodelling, and fibrosis on tissue stiffness, and reviews emerging techniques for non-invasive estimation of myocardial mechanical properties. The review also considers the potential of patient-specific cardiac digital twins for clinical decision support. Finally, it identifies key methodological challenges, unresolved questions, and future opportunities for advancing standardised mechanical characterisation and the clinical translation of cardiac biomechanics.