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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  MYBPC3  Δ25bp  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  &amp;lt; 0.0001), LV outflow tract peak velocity (m/s) (CI: 0.19 ± 0.07;  p  &amp;lt; 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 (LVID dia ) 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  MYBPC3  Δ25bp  is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.

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