South Asian-Specific MYBPC3Δ25bp Deletion Carriers Display Hypercontraction and Impaired Diastolic Function Under Exercise Stress

Sholeh Bazrafshan*, Robert Sibilia, Saavia Girgla, Shiv Kumar Viswanathan, Megan J. Puckelwartz, Kiranpal S. Sangha, Rohit R. Singh, Mashhood Kakroo, Roman Jandarov, David M. Harris, Jack Rubinstein, Richard C. Becker, Elizabeth M. McNally, Sakthivel Sadayappan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Article number766339
JournalFrontiers in Cardiovascular Medicine
StatePublished - 2021


  • 25bp deletion
  • DOSA study
  • hypertrophic cardiomyopathy
  • MYBPC3
  • myosin binding protein-C
  • South Asians
  • stress echocardiography
  • ventricular diastolic dysfunction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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