Zaitsev V V, Gurshchenkov A V, Mitrofanova L B, Ryzhkov A V, Kazakova E E, Badaev K D, Gordeev M L, Moiseeva O M
Almazov National Medical Research Centre.
Pavlov First Saint Petersburg State Medical University.
Kardiologiia. 2020 Jan 20;60(3):44-50. doi: 10.18087/cardio.2020.3.n561.
Objective To evaluate prospects for clinical use of circulating biomarkers for characterizing fibrotic changes in the myocardium of patients with hypertrophic cardiomyopathy (HCMP) with left ventricular (LV) outflow tract obstruction.Materials and Methods This was a prospective study with a 12-month follow-up period. The study included 47 patients (29 females and 18 males) with obstructive HCMP who were selected for septal reduction. Echocardiography (EchoCG), cardiac magnetic resonance imaging (MRI) and measurements of serum C-reactive protein, N-terminal pro-brain natriuretic peptide, and relevant circulating markers of fibrosis (TGF-β1, MMP-2,-9, TIMP-1, galectin-3, sST2, CITP, PICP, and PIIINP) were performed for all patients. All patients were evaluated at baseline and at 7 days, 6 and 12 months following surgical treatment. Morphometrical analysis of intraoperative biopsy samples was performed for evaluation of the degree of fibrotic changes. Patients received beta-blockers (95.7%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (34%), loop diuretics (68.1%), aldosterone antagonists (34%), and statins (66%).Results Women with HCMP were older and more frequently had additional risk factors (arterial hypertension). Men had a higher risk of sudden cardiac death. Histological study of intraoperative myocardial biopsy samples showed that the area of fibrotic changes was 13.9±6.9%. According to cardiac MRI mean area of delayed contrast enhancement was 8.7±3.3% of LV myocardial mass. No association was established between traditional cardiovascular risk factors and severity of myocardial fibrotic changes or levels of circulating fibrosis markers. Perhaps that was due to the modifying effect of the drug therapy received by HCMP patients. According to EchoCG maximum pressure gradient in the LV outflow tract before the surgical treatment was 88 (55; 192) mm Hg, and interventricular septal thickness was 22 (16; 32) mm. A considerable decrease (p=0.0002) in the LV outflow tract gradient was observed after myectomy in all patients. At the same time, the left ventricular dimension, which tended to decrease in the early postoperative period, returned to baseline values by the 6th month of follow-up.Conclusion The study confirmed the increase in relevant circulating markers of fibrosis in patients with obstructive HCMP. At the same time, no correlation was observed between levels of circulating biomarkers and severity of fibrosis according to data of histology and cardiac MRI, which was probably due to the modifying effect of drug therapy and limited sampling.
目的 评估循环生物标志物在表征伴有左心室(LV)流出道梗阻的肥厚型心肌病(HCMP)患者心肌纤维化改变方面的临床应用前景。
材料与方法 这是一项为期12个月随访期的前瞻性研究。该研究纳入了47例因室间隔减容而入选的梗阻性HCMP患者(29例女性和18例男性)。对所有患者进行了超声心动图(EchoCG)、心脏磁共振成像(MRI)以及血清C反应蛋白、N末端脑钠肽前体和相关纤维化循环标志物(转化生长因子-β1、基质金属蛋白酶-2、-9、金属蛋白酶组织抑制因子-1、半乳糖凝集素-3、可溶性生长刺激表达基因2蛋白、交联羧基末端肽、I型前胶原氨基端前肽和III型前胶原氨基端肽)的检测。所有患者在基线时以及手术治疗后7天、6个月和12个月进行评估。对术中活检样本进行形态计量分析以评估纤维化改变的程度。患者接受了β受体阻滞剂(95.7%)、血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂(34%)、袢利尿剂(68.1%)、醛固酮拮抗剂(34%)和他汀类药物(66%)治疗。
结果 HCMP女性患者年龄较大,且更常伴有其他危险因素(动脉高血压)。男性发生心源性猝死的风险较高。术中心肌活检样本的组织学研究显示,纤维化改变的面积为13.9±6.9%。根据心脏MRI,延迟强化的平均面积为左心室心肌质量的8.7±3.3%。传统心血管危险因素与心肌纤维化改变的严重程度或循环纤维化标志物水平之间未建立关联。这可能是由于HCMP患者接受的药物治疗的调节作用。根据EchoCG,手术治疗前左心室流出道的最大压力梯度为88(55;192)mmHg,室间隔厚度为22(16;32)mm。所有患者在心肌切除术后左心室流出道梯度均有显著下降(p=0.0002)。同时,左心室尺寸在术后早期有减小趋势,但在随访第6个月时恢复到基线值。
结论 该研究证实梗阻性HCMP患者相关纤维化循环标志物增加。同时,根据组织学和心脏MRI数据,未观察到循环生物标志物水平与纤维化严重程度之间的相关性,这可能是由于药物治疗的调节作用和取样有限所致。