Enhanced structural reverse remodeling following LVAD support in patients with TTN truncating variants.
- 1Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Abstract
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.
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BibTeX
@article{richards2026enhanced,
title = {{Enhanced structural reverse remodeling following LVAD support in patients with TTN truncating variants.}},
author = {Donald Richards and Robert M Cole and Michelle Kittleson and Daniel Mitchell and Vahid Yazdi and Meshe Chonde and Laura DiChiacchio and Lawrence Czer and Jaime Moriguchi and Jon Kobashigawa and Evan P Kransdorf},
journal = {JHLT open},
year = {2026},
month = sep,
doi = {10.1016/j.jhlto.2026.100688},
url = {https://europepmc.org/article/MED/42927226},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Enhanced structural reverse remodeling following LVAD support in patients with TTN truncating variants.
AU - Donald Richards
AU - Robert M Cole
AU - Michelle Kittleson
AU - Daniel Mitchell
AU - Vahid Yazdi
AU - Meshe Chonde
AU - Laura DiChiacchio
AU - Lawrence Czer
AU - Jaime Moriguchi
AU - Jon Kobashigawa
AU - Evan P Kransdorf
PY - 2026
DA - 2026/09/21
JO - JHLT open
DO - 10.1016/j.jhlto.2026.100688
UR - https://europepmc.org/article/MED/42927226
AB - 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.
SN - 2950-1334
ER -