Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

背景：可通过基因检测鉴定导致肥厚型心肌病 (HCM) 的致病性 DNA 变异 (G+) 的携带者。作为 HCM 的临床前表现，已经提出了几种异常，其中一些可以通过心血管磁共振 (CMR) 来识别。在这项研究中，我们评估了 G+/左心室肥厚阴性 (LVH-) 受试者和健康对照之间的形态学差异，并检查了 CMR 衍生变量是否可用于预测肌节基因变异。

方法：我们研究了 57 名最大壁厚 (MWT) < 13 mm 的 G+ 受试者，并将他们与 40 名年龄和性别匹配的健康对照组进行了比较。受试者接受 CMR，包括形态学、体积和功能评估。进行逻辑回归分析以确定预测性 CMR 特征，由此构建 G+ 状态的评分系统。

结果：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突出的钩状结构。由前基底钩、多个心肌隐窝、右心室/左心室比、MWT/PWT 比和 MWT/左心室质量比组成的模型预测 G+ 状态，曲线下面积为 0.92 [0.87–0.97]。≥3 分仅出现在 G+ 受试者中，识别出 56% 的 G+/LVH- 人群。

结论：包含 CMR 衍生变量的评分系统正确识别了 56% 的 G+ 受试者。我们的结果提供了对 G+/LVH- 受试者的广泛表型谱的进一步见解，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 和我们的目标评分系统可用于检测可能的 G+ 携带者并帮助规划控制间隔。