van der Velde Nikki, Huurman Roy, Hassing H Carlijne, Budde Ricardo P J, van Slegtenhorst Marjon A, Verhagen Judith M A, Schinkel Arend F L, Michels Michelle, Hirsch Alexander
Department of Cardiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, Netherlands.
Department of Radiology and Nuclear Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, Netherlands.
Front Cardiovasc Med. 2021 Sep 17;8:727405. doi: 10.3389/fcvm.2021.727405. eCollection 2021.
Carriers of pathogenic DNA variants (G+) causing hypertrophic cardiomyopathy (HCM) can be identified by genetic testing. Several abnormalities have been brought forth as pre-clinical expressions of HCM, some of which can be identified by cardiovascular magnetic resonance (CMR). In this study, we assessed morphological differences between G+/left ventricular hypertrophy-negative (LVH-) subjects and healthy controls and examined whether CMR-derived variables are useful for the prediction of sarcomere gene variants. We studied 57 G+ subjects with a maximal wall thickness (MWT) < 13 mm, and compared them to 40 healthy controls matched for age and sex on a group level. Subjects underwent CMR including morphological, volumetric and function assessment. Logistic regression analysis was performed for the determination of predictive CMR characteristics, by which a scoring system for G+ status was constructed. G+/LVH- subjects were subject to alterations in the myocardial architecture, resulting in a thinner posterior wall thickness (PWT), higher interventricular septal wall/PWT ratio and MWT/PWT ratio. Prominent hook-shaped configurations of the anterobasal segment were only observed in this group. A model consisting of the anterobasal hook, multiple myocardial crypts, right ventricular/left ventricular ratio, MWT/PWT ratio, and MWT/left ventricular mass ratio predicted G+ status with an area under the curve of 0.92 [0.87-0.97]. A score of ≥3 was present only in G+ subjects, identifying 56% of the G+/LVH- population. A score system incorporating CMR-derived variables correctly identified 56% of G+ subjects. Our results provide further insights into the wide phenotypic spectrum of G+/LVH- subjects and demonstrate the utility of several novel morphological features. If genetic testing for some reason cannot be performed, CMR and our purposed score system can be used to detect possible G+ carriers and to aid planning of the control intervals.
通过基因检测可识别出携带导致肥厚型心肌病（HCM）的致病性DNA变异（G+）的个体。已有多种异常情况被提出作为HCM的临床前表现，其中一些可通过心血管磁共振成像（CMR）识别。在本研究中，我们评估了G+/左心室肥厚阴性（LVH-）受试者与健康对照之间的形态学差异，并检查CMR衍生变量是否有助于预测肌节基因变异。我们研究了57名最大壁厚（MWT）<13mm的G+受试者，并在组水平上将他们与40名年龄和性别匹配的健康对照进行比较。受试者接受了包括形态学、容积和功能评估的CMR检查。进行逻辑回归分析以确定预测性CMR特征，据此构建了G+状态评分系统。G+/LVH-受试者的心肌结构发生改变，导致后壁厚度（PWT）变薄、室间隔壁/PWT比值和MWT/PWT比值升高。仅在该组中观察到前基底节段显著的钩状形态。由前基底钩、多个心肌隐窝、右心室/左心室比值、MWT/PWT比值和MWT/左心室质量比值组成的模型预测G+状态的曲线下面积为0.92[0.87-至0.97]。≥3分仅出现在G+受试者中，可识别出56%的G+/LVH-人群。纳入CMR衍生变量的评分系统正确识别出56%的G+受试者。我们的结果为G+/LVH-受试者广泛的表型谱提供了进一步的见解，并证明了几种新形态特征的实用性。如果由于某种原因无法进行基因检测，CMR和我们提出的评分系统可用于检测可能的G+携带者并辅助控制间隔的规划。
