Genetic diagnosis in patients undergoing left ventricular assist device placement
P Nair, E Li-Wen Chu, L Beach, J Teuteberg, W Hiesinger, K Sallam, V Parikh, N TapaskarAbstract
Background
A large proportion of patients undergoing LVAD implantation have nonischemic cardiomyopathy, among whom inherited forms of cardiomyopathy are increasingly identified. In addition to implications for family screening, the prognostic value of genetic diagnosis in LVAD patients is not well understood.
Purpose
This study aimed to characterize the landscape of genetic variants in LVAD recipients and evaluate the relationship between confirmed or suspected genetic cardiomyopathies and clinical outcomes post-LVAD implantation at a single academic medical center.
Methods
We conducted a single-center retrospective study of 390 adult patients who underwent LVAD implantation between June 2010 and February 2024. Analyses were structured using two complementary cohort definitions: (1) referral for genetic testing, which was presumed to reflect clinical suspicion for a genetic cardiomyopathy, and (2) genetic testing results, categorized as clinically actionable variants (pathogenic/likely pathogenic [P/LP] variants) vs. nonactionable results (variants of uncertain significance [VUS], benign, or negative). Primary outcomes included post-LVAD complications including right ventricular failure (RVF) and one-year survival. Multivariate logistic regression was used to identify independent predictors of outcomes.
Results
Of the 390 patients, 134 (34%) were referred for genetic testing, and 68 completed it. P/LP variants were found in 24 patients (35%), with TTN variants being the most common (42%). In our referral-based analysis, referral for genetic testing was independently associated with improved 1-year survival (OR 3.35[ 1.79,6.29]; p<0.0001) in multivariate analysis. Among the cohort who completed genetic testing, patients with confirmed actionable variants did not have an increased prevalence of RVF when compared to those with non-actionable variants (37.5% vs 43.2%, p=0.65) Pre-implant moderate-to-severe RV dysfunction was an independent predictor of worse 1-year survival (OR 0.52[0.31,0.87], p=0.0103).
Conclusions
In this single-center study, causative genetic variants were not associated with worse LVAD outcomes, and patients undergoing genetic testing had lower rates of right ventricular failure and improved survival. These results suggest that an underlying genetic diagnosis should not be considered a contraindication for LVAD therapy, and may indicate that lower risk patients are more likely to be offered genetic testing.