Abstract | March 24, 2024

Interaction between Gene Mutations and Comorbidities on a Patient Cohort with Hypertrophic Cardiomyopathy

Pooja Nair, BS, UCSD School of Medicine, La Jolla, CA

Cody Kelso, MD, Internal Medicine, PGY1, UPMC, Pittsburgh, PA; Apurv Prabhakar, BS, UCSD, La Jolla, CA; Elizabeth Silver, Division of Cardiovascular Medicine, UCSD, La Jolla, CA; Jeffrey Ding, BS, UCSD School of Medicine, La Jolla, CA; Quan M Bui, MD, Assistant Clinical Professor, Division of Cardiovascular Medicine, Department of Medicine, UCSD, La Jolla, CA; Eric Adler, MD, Professor of Medicine, Division of Cardiovascular Medicine, Department of Medicine, UCSD, La Jolla, CA; Kimberly N Hong, MD, MHSA, Assistant Professor of Medicine, Division of Cardiovascular Medicine, Department of Medicine, UCSD, La Jolla, CA

Learning Objectives

  1. Discuss effects of gene mutations on outcomes for patients with hypertrophic cardiomyopathy
  2. Describe the interaction between metabolic syndrome comorbidities and genetic HCM predisposition on patient outcomes

Background/Knowledge Gap: Hypertrophic Cardiomyopathy (HCM), an inherited cardiomyopathy, affects 1 in 500 Americans. Metabolic syndrome which includes diabetes mellitus (DM), hyperlipidemia, obesity and hypertension affects 20-30% of Americans(1). The goal of this study is to assess the impact of metabolic syndrome on disease severity in patients with HCM, stratifying by genotype positive and genotype negative patients.

Methods/Design: Data was collected from a single center of patients who underwent cardiomyopathy gene testing. Patients were identified using guideline diagnostic criteria for HCM(2). Patients were divided into genotype positive (pathogenic or likely pathogenic variants) and genotype negative (variant of unknown significance, likely benign, or benign variants) groups. Outcomes included a composite heart failure (HF) outcome and a composite major ventricular arrhythmia (MVA) outcome. Chi Square and Wilcoxon Testing were used for comparison analysis. Kaplan Meier curves with log-rank testing were used in time-to-event analysis.

Results/Findings: The study included an ethnically diverse cohort of 183 patients (61.2% male, 38.3% female, 53.1% non-white), with a median age of 50 years (IQR: 38-65 years). Compared with genotype(-) patients, genotype(+) patients had higher HF events (9.5% of genotype(-) patients and 33.3% of genotype(+) patients; p<0.0005) and MVA events (9.5% of genotype(-) patients and 28.1% of genotype(+) patients; p=0.001), with time-to-event analyses showing earlier median age of HF events (p<0.001) and MVA events (p<0.001) in the genotype(+) group (HF: 70 years; MVA: 75 years) vs the genotype(-) group (HF: 92 years). The prevalence of comorbid conditions in the total patient population was: 14.21% for diabetes mellitus (DM), 37.87% for hyperlipidemia, 31.15% for obesity, and 35.52% for hypertension. For genotype (+) patients, patients with DM had HF events at earlier ages with median age of HF event being 63 years versus 71 years in the non-DM group (p=0.0361). Comorbid conditions did not impact HF and MVA event rates in the negative genetics group.

Conclusions/Implications: Our analysis supports previous literature that severity of HCM is increased when patients have genotype(+) HCM. Additionally, the increased risk for HF outcome in those with DM in genotype(+) patients suggests additional epigenetic risk that warrants further research.

References and Resources

  1. Moore JX, Chaudhary N, Akinyemiju T. Metabolic Syndrome Prevalence by Race/Ethnicity and Sex in the United States, National Health and Nutrition Examination Survey, 1988–2012. Prev Chronic Dis 2017;14:160287.)
  2. Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL, Hung J, Joglar JA, Kantor P, Kimmelstiel C, Kittleson M, Link MS, Maron MS, Martinez MW, Miyake CY, Schaff HV, Semsarian C, Sorajja P. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2020 Dec 22;76(25):3022-3055. doi: 10.1016/j.jacc.2020.08.044. Epub 2020 Nov 20. PMID: 33229115.
Back to Abstracts