In silico analysis of sarcomere length effects on myocardial contraction and cardiac function using the living left...

The cardiac sarcomere length is a major determinant of myocardial contractility, influencing the length-tension relationship, calcium sensitivity, and preload dependence. In time-varying-elastance-based constitutive myocardial models, two fundamental sarcomere-length parameters are the unloaded sarcomere length, $L_r$ and the zero active tension length, $L_0$ . These parameters regulate calcium sensitivity and contraction duration, thereby shaping myocardial mechanical behavior. Although alterations in these parameters are implicated in sarcomere-related cardiomyopathies and have been widely studied for their effects on myocardial tension generation, their multiscale consequences-from tissue-level tension generation to organ-level pump performance-have not been systematically characterized. Motivated by this gap, we investigated how variations in $L_r$ and $L_0$ , individually and in combination, would modify global and regional left heart mechanics. The Living Left Heart Model implemented in Abaqus was used to simulate three scenarios: (1) $L_r$ variation from 1.75 to 1.95 µm with $L_0$ fixed at 1.58 µm, (2) $L_0$ variation from 1.48 to 1.68 µm with $L_r$ fixed at 1.85 µm, and (3) simultaneous variation of $L_r$ and $L_0$ with their difference kept constant. Analyses were performed from the tissue scale-evaluating length-tension relationships and active stress evolution-to the organ scale, assessing fiber stretch, fiber active stress, regional strain patterns, and overall cardiac function such as pressure-volume loops. Variation in $L_r$ primarily modulated contractility: at the tissue level, $L_r$ influenced the duration of active tension, and at the organ level, increased $L_r$ enhanced ventricular systolic performance whereas decreased $L_r$ impaired it, reflecting changes in inotropy. Changes in $L_0$ were even more pronounced; at the tissue level, $L_0$ shifted peak active stress, and at the organ level, it induced diastolic dysfunction-like behavior with altered filling and relaxation. We further confirmed that the sarcomere length difference (SLD, $L_r-L_0$ ) determined the peak active stress, and that distinct parameter sets with the same SLD often produced similar organ-level responses. Collectively, these findings identify $L_r$ and $L_0$ as mechanistic control axes that shape a continuum of left heart functional phenotypes, rather than mapping one-to-one onto a single disease entity. This framework suggests that sarcomere-level parameters can be used to systematically explore and emulate sarcomere-related cardiac pathophysiology in silico.