Key result
Progressive remodeling in simulated MYH7-HCM impairs diastolic filling despite preserved ejection fraction.
Why the study?
Diastolic dysfunction in hypertrophic cardiomyopathy reflects changes in sarcomeric function, electrophysiology, ventricular structure, and myocardial mechanics, but their individual effects on filling remain difficult to determine clinically.
In silico electromechanical modeling of MYH7-related non-obstructive hypertrophic cardiomyopathy demonstrates that diastolic dysfunction and impaired myocardial deformation occur prior to overt hypertrophy and worsen with structural, mechanical, and ionic remodeling despite preserved ejection fraction.
Answers are grounded in this paper and cite their sources.
Regional strain may detect preclinical diastolic impairment in modeled cardiomyopathy; leaves open clinical translation pending prospective validation.
Aims: Diastolic dysfunction in hypertrophic cardiomyopathy reflects changes in sarcomeric function, electrophysiology, ventricular structure, and myocardial mechanics. Their effects on filling remain difficult to determine clinically. We sought to dissect these effects in MYH7-related non-obstructive hypertrophic cardiomyopathy progression. Methods and results: We developed a human biventricular electromechanical model linking electrophysiology and calcium handling to contraction, ventricular mechanics, haemodynamics, electrocardiography, and myocardial strain. Stage I represented MYH7 sarcomeric dysfunction before hypertrophy; Stage II added septal hypertrophy; Stage III added increased myocardial stiffness. Secondary ionic remodelling was examined at each stage and severity. Sarcomeric dysfunction alone generated a low-volume hypercontractile phenotype before overt hypertrophy. Septal hypertrophy further constrained chamber filling, whereas myocardial stiffening exacerbated diastolic dysfunction and regional mechanical heterogeneity. Secondary ionic remodelling produced marked repolarisation abnormalities but, importantly, also prolonged calcium-tension dynamics and impaired relaxation, reducing ventricular filling to an extent comparable with structural remodelling in some disease states. Increasing ionic-remodelling severity progressively amplified these effects. Despite preserved ejection fraction throughout progression, ventricular volumes decreased while global and regional myocardial deformation deteriorated. Conclusion: Diastolic dysfunction was evident before overt hypertrophy and worsened as structural, mechanical, and ionic abnormalities were added. Preserved ejection fraction did not reflect reduced ventricular filling or deterioration in myocardial strain. Regional mechanical measures may therefore reveal disease burden not captured by ejection fraction alone. By separating individual disease mechanisms, in silico modelling may help link measurable biomarkers to their underlying causes and support mechanism-based patient stratification.
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Hasaballa et al. (2026) studied MYH7-related non-obstructive hypertrophic cardiomyopathy. Simulated sarcomeric dysfunction, septal hypertrophy, myocardial stiffening, and secondary ionic remodelling vs. Baseline / earlier disease stages (Stages I-III) was evaluated on Diastolic dysfunction, ventricular filling, and regional myocardial deformation across simulated disease stages. In a 3-stage biventricular electromechanical model of MYH7-HCM, sarcomeric, structural, and ionic remodelling progressively impaired relaxation and filling despite preserved ejection fraction.
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