Key result
Diffuse interstitial fibrosis is linked to ~2.3-fold higher odds of actionable genetic variants in advanced heart failure.
Why the study?
Genetic testing practices are understudied in patients with end-stage heart failure undergoing advanced therapies despite the importance of identifying genetic etiologies.
Observational (n=529)
No
Odds Ratio: 2.29 (95% CI 1.08–4.86)
p-value: p=0.03
Despite a high burden of genetic disease in end-stage heart failure patients, genetic testing and counseling are underutilized, though pathology findings like interstitial fibrosis may help identify patients with genetic etiologies.
Pathology fibrosis may flag genetic HF etiologies for testing; leaves open prospective validation before practice change.
BACKGROUND: Genetic cardiomyopathies (CMs) are increasingly recognized as causes of end-stage heart failure (ESHF). Identification of a genetic etiology in ESHF has important prognostic and family implications. However, genetic testing practices are understudied in patients with ESHF. METHODS: This single-center, retrospective study included consecutive patients with ESHF who underwent heart transplantation (HT) or left ventricular assist device (LVAD) implantation between 2018 and 2023. Data, including genetic testing and pathology reports, were collected from the electronic medical records. Analyses of demographic and clinical characteristics were stratified by genetic-testing completion and the presence of clinically actionable variants. Logistic regression was performed to evaluate for associations between histology findings and genetic variants. RESULTS: A total of 529 adult patients (mean age 57 years) were included in the study and were predominantly male (79%, 422/529) and non-white (61%, 322/529). Genetic testing was performed in 54% (196/360) of patients with either nonischemic or mixed CMs. A clinically actionable result was identified in 36% (70/196) of patients, of whom only 43% (30/70) had genetic counselor referrals. The most common genetic variants were TTN (32%, 24/75), MYBPC3 (13%, 10/75) and TTR (11%, 8/75). Clinically actionable variants were identified in patients with known heart failure precipitators such as alcohol use. In multivariable analysis, the presence of interstitial fibrosis, specifically diffuse, on pathology was significantly associated with a clinically actionable variant (aOR 2.29, 95% CI [1.08-4.86]; P = 0.03). CONCLUSION: Patients with ESHF and with nonischemic or mixed CM who were undergoing advanced therapies had low uptakes of genetic services, including testing and counselors, despite high burdens of genetic disease. Pathology findings such as interstitial fibrosis may provide insight into genetic etiology. The underuse of services suggests a need for implementation strategies to improve uptake.
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Silver et al. (2024) conducted an observational in End-stage heart failure (n=529). Interstitial fibrosis on pathology was evaluated on Presence of a clinically actionable genetic variant (aOR 2.29, 95% CI 1.08-4.86, p=0.03). Diffuse interstitial fibrosis on pathology was significantly associated with a clinically actionable genetic variant in patients with end-stage heart failure (aOR 2.29; 95% CI 1.08-4.86; P=0.03).
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