Drug Effects on Human Cardiac Muscle Contraction and LV Function

From sarcomere kinetics to whole-heart PV loop

Starting from measured ATPase kinetics and fiber mechanics data, MUSICO simulated the effects of mavacamten and disopyramide on human HCM cardiac muscle twitch. Outputs were then passed to a whole-heart finite element model to predict left ventricular pressure-volume behavior.

Key findings:

1
Mavacamten: ~30% decrease in peak tension at full Ca²⁺ activation; ~50% reduction in twitch peak force.
2
Disopyramide: reduces Ca²⁺ transient peak → distinct kinetic mechanism from mavacamten.
3
LV PV loops: mavacamten shifts loop toward lower volumes and pressures (HCM hypercontractility corrected).
4
MUSICO vs. FE Heart: sarcomere-level predictions directionally consistent with whole-heart FE simulations.

This is the sarcomere-to-organ pipeline that turns fiber-level assay data into a mechanistically interpretable, human-translatable result.

References:
Tomasevic et al., Pharmaceutics 2023
Ma, Prodanovic, Mijailovich et al. PNAS 2024 · co-authored with BMS Cardiovascular Drug Discovery

MUSICO-predicted force-calcium relationship (left) and twitch tension transient (right) for human HCM cardiac muscle with and without mavacamten. Mavacamten reduces maximum active force by ~30% and peak twitch tension by ~50%, consistent with its mechanism of reducing available force-generating myosin heads.
Experimental twitch tension (A) and calcium transient (B) in human HCM cardiac muscle with and without disopyramide, alongside MUSICO (C) and MP surrogate (D) simulations. MUSICO accurately reproduces the experimental data by capturing disopyramide's primary mechanism through calcium transient modulation.
Finite element simulations of a patient-specific HCM left ventricle at peak systole showing wall displacement, intracavitary pressure, and blood flow velocity, without drug, with disopyramide, and with mavacamten. Both drugs reduce peak systolic pressure, with mavacamten producing the larger effect, consistent with its stronger sarcomere-level negative inotropic action.
Simulated pressure-volume loops for an HCM left ventricle model without drug, with mavacamten, and with disopyramide (FE + MP surrogate simulations). Both drugs shift the PV loop toward lower pressures and larger volumes, correcting HCM hypercontractility and moving toward a more physiological cardiac cycle.
FILAMENTECH LOGO-02-white

Human cardiac prediction from data you already have.

FilamenTech develops multiscale mechanistic simulation workflows that help drug-development teams translate assay, tissue, animal, mutation, and structural data into human-relevant cardiac and muscle predictions.

Boston • Belgrade

Linkedin

Explore

Company

Start with a focused pilot.

Evaluate mutation effects, drug responses, or translational hypotheses using mechanistic simulation workflows tailored to your program.

Discuss a project
See if your dataset fits

© 2026 FilamenTech. All rights reserved.

Created by Starter studio.