Related Experiment Video
Updated: Oct 26, 2026
Studying Left Ventricular Reverse Remodeling by Aortic Debanding in Rodents
Published on: July 14, 2021
Enhanced structural reverse remodeling following LVAD support in patients with TTN truncating variants
Donald Richards1, Robert M Cole1, Michelle Kittleson1
1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Background:
Myocardial recovery sufficient for left ventricular assist device (LVAD) explantation remains uncommon. Titin truncating variant (TTNtv)-associated cardiomyopathy demonstrates favorable reverse remodeling with medical therapy, but its remodeling potential during durable mechanical unloading is unknown.
Methods:
We conducted a retrospective, single-center study of adults undergoing HeartMate 3 LVAD implantation from 2016-2025. Patients were categorized as TTNtv-associated cardiomyopathy, other genetically characterized nonischemic cardiomyopathy (NICM), or ischemic cardiomyopathy (ICM). The primary endpoint was absolute change in left ventricular end-systolic volume index (LVESVI) during LVAD support. Multivariable and sensitivity analyses evaluated potential confounding and influential observations.
Results:
Among 51 patients, 7 had TTNtv-associated cardiomyopathy, 9 other NICM, and 35 ICM. TTNtv patients were younger than other NICM and ICM patients (40.5±15.8 vs 45.8±11.0 vs 67.4±9.3 years; P<0.001). Mean LVESVI decreased by 87.7±71.8 mL/m² in TTNtv patients compared with 30.4±28.3 mL/m² in other NICM and 32.6±30.6 mL/m² in ICM (P=0.039). Compared with ICM, TTNtv status remained associated with greater LVESVI reduction after adjustment for baseline LV end-diastolic diameter (β=-47.2 mL/m²; 95% CI, -75.9 to -18.4; P=0.002). Findings were directionally consistent across sensitivity analyses addressing age, post-LVAD guideline-directed medical therapy, follow-up duration, cardiomyopathy substrate, and influential observations. TTNtv patients more frequently met volumetric reverse remodeling criteria (85.7% vs 22.2% vs 57.1%; P=0.044).
Conclusions:
TTNtv-associated cardiomyopathy was associated with greater structural reverse remodeling during LVAD support, particularly LVESVI reduction. Although limited by the small TTNtv cohort and potential residual confounding, these hypothesis-generating findings suggest that genetic substrate may contribute to myocardial remodeling during mechanical unloading.
