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
Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States.
Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Front Cardiovasc Med. 2021 Dec 23;8:766339. doi: 10.3389/fcvm.2021.766339. eCollection 2021.
A 25-base pair (25bp) intronic deletion in the 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. As a pilot study, 10 asymptomatic SA carriers of the 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. 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; < 0.0001), LV outflow tract peak velocity (m/s) (CI: 0.19 ± 0.07; < 0.0001), and higher aortic valve (AV) peak velocity (m/s) (CI: 0.103 ± 0.08; = 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; = 0.038). Interestingly, LV end-diastolic diameter (LVID) was augmented in NCs in response to stress, while it did not increase in Δ25bp carriers (CI: 0.239 ± 0.125; = 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; = 0.0001), suggesting right ventricle functional differences between the two groups. These data support that is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.
在南亚人（SA）中富集的基因里，一个25个碱基对（25bp）的内含子缺失是迟发性左心室（LV）功能障碍、肥厚以及多种形式心肌病所致心力衰竭（HF）的风险等位基因。然而，该变异对运动参数的影响尚未得到评估。作为一项初步研究，对10名携带该变异的无症状SA个体（52.9±2.14岁）和10名年龄及性别匹配的非携带者（NC）（50.1±2.7岁）在基线状态以及运动应激条件下进行了评估，采用自行车运动超声心动图和连续心脏监测。两组之间的基线超声心动图参数并无差异。然而，在运动应激反应中，与NC相比，Δ25bp携带者的左心室射血分数（%）显著更高（CI：4.57±1.93；P<0.0001），左心室流出道峰值速度（m/s）显著更高（CI：0.19±0.07；P<0.0001），主动脉瓣（AV）峰值速度（m/s）也更高（CI：0.103±0.08；P = 0.01），并且舒张顺应性标志物E/A比值在Δ25bp携带者中显著更低（CI：0.107±0.102；P = 0.038）。有趣的是，在应激状态下，NC的左心室舒张末期直径（LVID）增大，而Δ25bp携带者的LVID并未增加（CI：0.239±0.125；P = 0.0002）。此外，作为右心室功能标志物的应激诱导右心室收缩期偏移速度s'（m/s）在两组中同样增加，但携带者的三尖瓣环平面收缩期偏移增加得更多（斜率：0.008；P = 0.0001），这表明两组之间存在右心室功能差异。这些数据支持该基因与应激条件下左心室过度收缩以及舒张功能受损相关。
