Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
PLoS One. 2019 Jun 14;14(6):e0217612. doi: 10.1371/journal.pone.0217612. eCollection 2019.
HCM is the most common inherited cardiomyopathy. Historically, there has been poor correlation between genotype and phenotype. However, CMR has the potential to more accurately assess disease phenotype. We characterized phenotype with CMR in a cohort of patients with confirmed HCM and high prevalence of genetic testing.
Patients with a diagnosis of HCM, who had undergone contrast-enhanced CMR were identified. Left ventricular mass index (LVMI) and volumes were measured from steady-state free precession sequences. Late gadolinium enhancement (LGE) was quantified using the full width, half maximum method. All patients were prospectively followed for the development of septal reduction therapy, arrhythmia or death.
We included 273 patients, mean age 51.2 ± 15.5, 62.9% male. Of those patients 202 (74.0%) underwent genetic testing with 90 pathogenic, likely pathogenic, or rare variants and 13 variants of uncertain significance identified. Median follow-up was 1138 days. Mean LVMI was 82.7 ± 30.6 and 145 patients had late gadolinium enhancement (LGE). Patients with beta-myosin heavy chain (MYH7) mutations had higher LV ejection fraction (68.8 vs 59.1, p<0.001) than those with cardiac myosin binding protein C (MYBPC3) mutations. Patients with MYBPC3 mutations were more likely to have LVEF < 55% (29.7% vs 4.9%, p = 0.005) or receive a defibrillator than those with MYH7 mutations (54.1% vs 26.8%, p = 0.020).
We found that patients with MYBPC3 mutations were more likely to have impaired ventricular function and may be more prone to arrhythmic events. Larger studies using CMR phenotyping may be capable of identifying additional characteristics associated with less frequent genetic causes of HCM.
肥厚型心肌病（HCM）是最常见的遗传性心肌病。从历史上看，基因型与表型之间的相关性一直很差。但是，CMR 有可能更准确地评估疾病表型。我们通过对一组经证实的 HCM 患者和遗传检测高患病率的患者进行 CMR 检查，对表型进行了特征描述。
确定了经过对比增强型 CMR 检查的 HCM 诊断患者。从稳态自由进动序列测量左心室质量指数（LVMI）和容量。使用全宽半最大值方法量化晚期钆增强（LGE）。所有患者均前瞻性随访，以评估室间隔减少治疗、心律失常或死亡的发生情况。
共纳入 273 例患者，平均年龄为 51.2 ± 15.5 岁，62.9%为男性。其中 202 例（74.0%）接受了基因检测，发现 90 种致病性、可能致病性或罕见变异体以及 13 种意义不明的变异体。中位随访时间为 1138 天。平均 LVMI 为 82.7 ± 30.6，145 例患者存在晚期钆增强（LGE）。β-肌球蛋白重链（MYH7）突变患者的左心室射血分数（LVEF）（68.8%比 59.1%，p<0.001）高于心肌肌球蛋白结合蛋白 C（MYBPC3）突变患者。与 MYH7 突变患者相比，MYBPC3 突变患者更有可能出现 LVEF<55%（29.7%比 4.9%，p=0.005）或植入除颤器（54.1%比 26.8%，p=0.020）。
我们发现 MYBPC3 突变患者更有可能出现心室功能受损，并且更有可能发生心律失常事件。使用 CMR 表型进行更大规模的研究可能能够确定与 HCM 较少见的遗传病因相关的其他特征。
