Abstract
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, Lr and the zero active tension length, L0 . 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 Lr and L0 , 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) Lr variation from 1.75 to 1.95 µm with L0 fixed at 1.58 µm, (2) L0 variation from 1.48 to 1.68 µm with Lr fixed at 1.85 µm, and (3) simultaneous variation of Lr and L0 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 Lr primarily modulated contractility: at the tissue level, Lr influenced the duration of active tension, and at the organ level, increased Lr enhanced ventricular systolic performance whereas decreased Lr impaired it, reflecting changes in inotropy. Changes in L0 were even more pronounced; at the tissue level, L0 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, Lr - L0 ) determined the peak active stress, and that distinct parameter sets with the same SLD often produced similar organ-level responses. Collectively, these findings identify Lr and L0 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.