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=8

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=<p><bold>Background:</bold> A 25-base pair (25bp) intronic deletion in the <italic>MYBPC3</italic> 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.</p><p><bold>Methods:</bold> As a pilot study, 10 asymptomatic SA carriers of the <italic>MYBPC3</italic><sup>Δ25bp</sup> 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.</p><p><bold>Results:</bold> 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; <italic>p</italic> &lt; 0.0001), LV outflow tract peak velocity (m/s) (CI: 0.19 ± 0.07; <italic>p</italic> &lt; 0.0001), and higher aortic valve (AV) peak velocity (m/s) (CI: 0.103 ± 0.08; <italic>p</italic> = 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; <italic>p</italic> = 0.038). Interestingly, LV end-diastolic diameter (LVID<sub>dia</sub>) was augmented in NCs in response to stress, while it did not increase in Δ25bp carriers (CI: 0.239 ± 0.125; <italic>p</italic> = 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; <italic>p</italic> = 0.0001), suggesting right ventricle functional differences between the two groups.</p><p><bold>Conclusions:</bold> These data support that <italic>MYBPC3</italic><sup>Δ25bp</sup> is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.</p>