Genetic Testing Practices and Pathological Assessments in End Stage Heart Failure Patients Undergoing Heart Transplantation and Left Ventricular Assist Device.

Genetic testing advanced therapies cardiomyopathy cascade testing genetic counseling heart transplant left ventricular assist device

Journal

Journal of cardiac failure
ISSN: 1532-8414
Titre abrégé: J Card Fail
Pays: United States
ID NLM: 9442138

Informations de publication

Date de publication:
23 Oct 2024
Historique:
received: 02 07 2024
revised: 25 09 2024
accepted: 25 09 2024
medline: 26 10 2024
pubmed: 26 10 2024
entrez: 25 10 2024
Statut: aheadofprint

Résumé

Genetic cardiomyopathies (CM) 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 ESHF patients. This single-center, retrospective study included consecutive ESHF patients who underwent heart transplantation (HT) or left ventricular assist device (LVAD) from 2018 to 2023. Data, including genetic testing and pathology reports, were collected from the electronic medical record. Analyses of demographic and clinical characteristics were stratified by genetic testing completion and presence of clinically actionable variant. Logistic regression was performed to evaluate for associations between histology findings and genetic variants. 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 non-ischemic or mixed CM. A clinically actionable result was identified in 36% (70/196) of patients, of which, only 43% (30/70) had a genetic counselor referral. 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, 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). ESHF patients with non-ischemic or mixed CM undergoing advanced therapies had a low uptake of genetic services, including testing and counselors, despite a high burden of genetic disease. Pathology findings, such as interstitial fibrosis, may provide insight into genetic etiology. The underutilization of services suggests a need for implementation strategies to improve uptake.

Sections du résumé

BACKGROUND BACKGROUND
Genetic cardiomyopathies (CM) 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 ESHF patients.
METHODS METHODS
This single-center, retrospective study included consecutive ESHF patients who underwent heart transplantation (HT) or left ventricular assist device (LVAD) from 2018 to 2023. Data, including genetic testing and pathology reports, were collected from the electronic medical record. Analyses of demographic and clinical characteristics were stratified by genetic testing completion and presence of clinically actionable variant. Logistic regression was performed to evaluate for associations between histology findings and genetic variants.
RESULTS 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 non-ischemic or mixed CM. A clinically actionable result was identified in 36% (70/196) of patients, of which, only 43% (30/70) had a genetic counselor referral. 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, 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 CONCLUSIONS
ESHF patients with non-ischemic or mixed CM undergoing advanced therapies had a low uptake of genetic services, including testing and counselors, despite a high burden of genetic disease. Pathology findings, such as interstitial fibrosis, may provide insight into genetic etiology. The underutilization of services suggests a need for implementation strategies to improve uptake.

Identifiants

pubmed: 39454940
pii: S1071-9164(24)00885-6
doi: 10.1016/j.cardfail.2024.09.015
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Elizabeth Silver (E)

Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.

Alessia Argiro (A)

Cardiomyopathy Unit, University of Florence, Florence, Italy.

Sarah S Murray (SS)

Division of Laboratory and Genomic Medicine, Department of Pathology, University of California, San Diego, La Jolla, CA, USA.

Lauren Korty (L)

Division of Genetic Counseling, University of California, San Diego, La Jolla, CA, USA.

Grace Lin (G)

Division of Anatomic Pathology, Department of Pathology, University of California, San Diego, La Jolla, CA, USA.

Victor Pretorius (V)

Division of Cardiovascular and Thoracic Surgery, Department of Surgery, University of California, San Diego, La Jolla, CA, USA.

Marcus Urey (M)

Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.

Kimberly N Hong (KN)

Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.

Eric D Adler (ED)

Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.

Quan M Bui (QM)

Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: q3bui@health.ucsd.edu.

Classifications MeSH