Ichikawa Mizuki, Nakamori Shiro, Ishida Masaki, Okamoto Ryuji, Ito Rie, Ishiura Junko, Ishiyama Masaki, Omori Taku, Moriwaki Keishi, Sugiura Emiyo, Fujimoto Naoki, Kurita Tairo, Ichikawa Yasutaka, Kitagawa Kakuya, Imanaka-Yoshida Kyoko, Sakuma Hajime, Dohi Kaoru
Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
JACC Adv. 2025 Jul 24;4(8):102013. doi: 10.1016/j.jacadv.2025.102013.
DNA damage in cardiomyocytes is a key pathological pathway in heart failure progression. It is a reversible process that precedes apoptosis and fibrosis. However, the utility of cardiovascular magnetic resonance T mapping for assessing DNA damage is uncertain.
This study aimed to evaluate the relationship between T mapping and cardiomyocyte DNA damage in patients with dilated cardiomyopathy (DCM).
We identified 36 recent-onset DCM patients undergoing endomyocardial biopsy and serial 3T cardiovascular magnetic resonance before and after guideline-directed therapy. Extracellular volume (ECV) was quantified from native and postcontrast T mapping. DNA damage was assessed via poly(ADP-ribose) quantification in biopsy specimens, alongside collagen volume fraction (CVF) measurement.
Native T and ECV showed a strong correlation with histological CVF (r = 0.62 and r = 0.67, respectively; P < 0.001), while native T moderately correlated with the severity of cardiomyocyte DNA damage (r = 0.41, P = 0.01), but ECV did not. This association remained significant after controlling for CVF. Patients with substantial DNA damage have significantly higher native T for an equivalent ECV (P = 0.004). In the absence of severe fibrosis, myocardial tissue recovery following guideline-directed therapy, along with improvements in left ventricular ejection fraction and reductions in left ventricular cavities, was associated with baseline DNA damage (r = -0.49, P = 0.004) but not with CVF (r = -0.17, P = 0.38).
Native T mapping effectively detects DNA damage and fibrosis, revealing different pathophysiological mechanisms behind the increased native T and ECV. A disproportionate increase in native T relative to ECV suggests early myocardial injury preceding fibrosis in DCM, with potential implications for myocardial tissue recovery after guideline-directed therapy.
心肌细胞中的DNA损伤是心力衰竭进展的关键病理途径。它是一个先于细胞凋亡和纤维化的可逆过程。然而，心血管磁共振T成像评估DNA损伤的效用尚不确定。
本研究旨在评估扩张型心肌病（DCM）患者T成像与心肌细胞DNA损伤之间的关系。
我们纳入了36例近期发病的DCM患者，这些患者在接受指南指导的治疗前后均接受了心内膜心肌活检和系列3T心血管磁共振检查。通过原始及对比后T成像定量细胞外容积（ECV）。在活检标本中通过聚（ADP - 核糖）定量评估DNA损伤，并测量胶原容积分数（CVF）。
原始T值和ECV与组织学CVF呈强相关（分别为r = 0.62和r = 0.67；P < 0.001），而原始T值与心肌细胞DNA损伤的严重程度呈中度相关（r = 0.41，P = 0.01），但ECV与心肌细胞DNA损伤无相关性。在控制CVF后，这种关联仍然显著。对于同等的ECV，DNA损伤严重的患者原始T值显著更高（P = 0.004）。在没有严重纤维化的情况下，指南指导的治疗后心肌组织恢复以及左心室射血分数的改善和左心室腔的缩小与基线DNA损伤相关（r = -0.49，P = 0.004），但与CVF无关（r = -0.17，P = 0.38）。
原始T成像可有效检测DNA损伤和纤维化，揭示原始T值和ECV升高背后不同的病理生理机制。相对于ECV，原始T值不成比例地增加表明DCM中纤维化之前存在早期心肌损伤，这对指南指导的治疗后心肌组织恢复具有潜在意义。
