South Asian-Specific MYBPC3Δ25bp Deletion Carriers Display Hypercontraction and Impaired Diastolic Function Under Exercise Stress
Year: 2021
Type: article
Study design: Observational Study
Abstract: Background: A 25-base pair (25bp) intronic deletion in the MYBPC3 gene enriched in South Asians (SAs) is a risk allele for late-onset left ventricular (LV) dysfunction, hypertrophy, and heart failure (HF) with several forms of cardiomyopathy. However, the effect of this variant on exercise parameters has not been evaluated. Methods: As a pilot study, 10 asymptomatic SA carriers of the MYBPC3Δ25bp variant (52.9 ± 2.14 years) and 10 age- and gender-matched non-carriers (NCs) (50.1 ± 2.7 years) were evaluated at baseline and under exercise stress conditions using bicycle exercise echocardiography and continuous cardiac monitoring. Results: Baseline echocardiography parameters were not different between the two groups. However, in response to exercise stress, the carriers of Δ25bp had significantly higher LV ejection fraction (%) (CI: 4.57 ± 1.93; p < 0.0001), LV outflow tract peak velocity (m/s) (CI: 0.19 ± 0.07; p < 0.0001), and higher aortic valve (AV) peak velocity (m/s) (CI: 0.103 ± 0.08; p = 0.01) in comparison to NCs, and E/A ratio, a marker of diastolic compliance, was significantly lower in Δ25bp carriers (CI: 0.107 ± 0.102; p = 0.038). Interestingly, LV end-diastolic diameter (LVIDdia) was augmented in NCs in response to stress, while it did not increase in Δ25bp carriers (CI: 0.239 ± 0.125; p = 0.0002). Further, stress-induced right ventricular systolic excursion velocity s' (m/s), as a marker of right ventricle function, increased similarly in both groups, but tricuspid annular plane systolic excursion increased more in carriers (slope: 0.008; p = 0.0001), suggesting right ventricle functional differences between the two groups. Conclusions: These data support that MYBPC3Δ25bp is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.
Institutions: University of Cincinnati, Northwestern University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
Awards: G1617165148, Channelopathies and Cardiomyopathies Among Sudden Deaths in the Young, G2659230099, G300576834, American Heart Association - Summer Undergraduate Research Fellowship (AHA-SURF), G4150767915, G5197370922, G523440871, Cardiomyopathy Genomes Project, Slow myosin binding protein-C in skeletal muscle physiology, G5501775048, A novel polymorphic MYBPC3 variant causes hypertrophic cardiomyopathy in US-South Asian descendants, Unfolded Protein Response and ER-Stress in Hypertrophic Cardiomyopathy, A polymorphic MYBPC3 variant as a major risk factor of cardiomyopathy in South Asian descendants, Molecular mechanism of hypertrophic cardiomyopathy in populations of South Asian descendants, IGF-2R is a new therapeutic target for cardiac ischemia-reperfusion injury, Molecular Mechanisms of Cardiac Arrhythmias in Patients with Compound Mutations, Fast myosin binding protein-C and cardiac contractility in heart failure, Stimulating Access to Research in the University of Cincinnati Internal Medicine Residency Program, G944649683
OpenAlex ID: W4200439591