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

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.766339

DOI=10.3389/fcvm.2021.766339

ISSN=2297-055X

ABSTRACT=Background: A 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 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 noncarriers (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 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 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.