Division of Cardiology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, South Korea.
Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea.
J Cardiovasc Magn Reson. 2021 Mar 4;23(1):18. doi: 10.1186/s12968-021-00718-3.
Myocardial fibrosis is an important prognostic factor in hypertrophic cardiomyopathy (HCM). However, the contribution from a wide spectrum of genetic mutations has not been well defined. We sought to investigate effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in HCM.
In 133 HCM patients, comprehensive genetic analysis was performed in 82 nuclear DNA (33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNA. In all patients, cardiovascular magnetic resonance (CMR) was performed, including 16-segmental thickness, late gadolinium enhancement (LGE), native and post-T1, extracellular volume fraction (ECV), and T2, along with echo-Doppler evaluations.
Patients with sarcomere mutation (SM, n = 41) had higher LGE involved segment, % LGE mass, ECV and lower post-T1 compared to patients without SM (n = 92, all p < 0.05). When classified into, non-mutation (n = 67), only mitochondria-related mutation (MM, n = 24), only-SM (n = 36) and both SM and MM (n = 5) groups, only-SM group had higher ECV and LGE than the non-mutation group (all p < 0.05). In non-LGE-involved segments, ECV was significantly higher in patients with SM. Within non-SM group, patients with any sarcomere variants of uncertain significance had higher echocardiographic Doppler E/e' (p < 0.05) and tendency of higher LGE amount and ECV (p > 0.05). However, MM group did not have significantly higher ECV or LGE amount than non-mutation group.
SMs are significantly related to increase in myocardial fibrosis. Although, some HCM patients had pathogenic MMs, it was not associated with an increase in myocardial fibrosis.
心肌纤维化是肥厚型心肌病（HCM）的一个重要预后因素。然而，广泛的基因突变的贡献尚未得到很好的定义。我们试图研究肌节和线粒体相关突变对 HCM 心肌纤维化的影响。
在 133 名 HCM 患者中，对 82 个核 DNA（33 个肌节相关基因、5 个表型基因和 44 个与线粒体心肌病相关的核基因）和 37 个线粒体 DNA 进行了全面的基因分析。在所有患者中，均进行了心血管磁共振（CMR）检查，包括 16 节段厚度、晚期钆增强（LGE）、原生和 T1 后、细胞外容积分数（ECV）和 T2，以及回声多普勒评估。
肌节突变（SM）患者的 LGE 受累节段、%LGE 质量、ECV 较高，T1 后时间较短，与无 SM 患者（n=92）相比，所有差异均有统计学意义（均 p<0.05）。当分为非突变（n=67）、仅线粒体相关突变（MM，n=24）、仅 SM（n=36）和 SM 和 MM 均有（n=5）组时，仅 SM 组的 ECV 和 LGE 高于非突变组（均 p<0.05）。在非 LGE 受累节段，SM 患者的 ECV 明显较高。在非 SM 组中，任何肌节不确定意义的变异患者的超声心动图多普勒 E/e'均较高（p<0.05），且 LGE 量和 ECV 较高的趋势（p>0.05）。然而，MM 组的 ECV 或 LGE 量并不明显高于非突变组。
SM 与心肌纤维化的增加显著相关。尽管一些 HCM 患者存在致病性 MM，但与心肌纤维化的增加无关。
