心肌纤维化发生在继发于二尖瓣反流(MR)的终末期心力衰竭中,但目前尚不清楚这是否在出现症状或心肌功能障碍之前出现。本研究旨在通过组织学表征慢性重度原发性MR中的心肌纤维化,将其与心血管磁共振(CMR)成像的组织表征进行比较,并调查与症状的关联,左心室(LV)功能,和锻炼能力。
具有I类或IIa类手术适应症的患者接受了CMR和心肺运动测试。在手术时进行LV活检,并且与没有心脏病理学的尸检对照相比,使用胶原体积分数(CVFmean)在组织学上量化纤维化程度。
招募了120例连续患者(64±13岁;71%为男性);105例患者接受了MV修复,15例选择了保守治疗。在86例患者中获得LV活检(总共234个活检样本)。与8例尸检对照相比,MR患者的纤维化更多(中位数:14.6%[四分位距7.4-20.3]vs.3.3%[2.6-6.1],P<0.001);这种差异在无症状患者中仍然存在(CVFmean13.6%[6.3-18.8],P<0.001),但在NYHAII-III症状性MR中,纤维化的严重程度并未显著升高(CVFmean15.7%[9.9-23.1](P=0.083).活检部位的纤维化呈斑片状(组内相关性0.23,95%CI0.08-0.39,P=0.001)。在CVFmean和CMR组织表征[天然T1、细胞外体积(ECV)或晚钆增强]或LV功能测量[LV射血分数(LVEF)之间没有发现显著的关系。全局纵向应变(GLS)]。尽管ECV的范围很小(27.3±3.2%),ECV与左心室功能的多项指标相关(LVEF:Rho=-0.22,P=0.029,GLS:Rho=0.29,P=0.003),以及NTproBNP(Rho=0.54,P<0.001)和运动能力(%PredVO2max:R=-0.22,P=0.030)。
慢性原发性MR患者在症状发作前纤维化增加。由于纤维化的斑块性质,CMR衍生的ECV可能是整体心肌状况的更好标志物。临床试验注册二尖瓣FINDER研究;临床试验NCT02355418,2015年2月4日注册,https://clinicaltrials.gov/ct2/show/NCT02355418。
Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity.
Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction (CVFmean) compared to autopsy controls without cardiac pathology.
120 consecutive patients (64 ± 13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fibrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4-20.3] vs. 3.3% [2.6-6.1], P < 0.001); this difference persisted in the asymptomatic patients (CVFmean 13.6% [6.3-18.8], P < 0.001), but severity of fibrosis was not significantly higher in NYHA II-III symptomatic MR (CVFmean 15.7% [9.9-23.1] (P = 0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08-0.39, P = 0.001). No significant relationships were identified between CVFmean and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho = - 0.22, P = 0.029, GLS: Rho = 0.29, P = 0.003), as well as NTproBNP (Rho = 0.54, P < 0.001) and exercise capacity (%PredVO2max: R = - 0.22, P = 0.030).
Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418.