Nakano Stephanie J, Siomos Austine K, Garcia Anastacia M, Nguyen Hieu, SooHoo Megan, Galambos Csaba, Nunley Karin, Stauffer Brian L, Sucharov Carmen C, Miyamoto Shelley D
Department of Pediatrics, Division of Cardiology, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO.
Department of Pediatrics, Division of Pathology, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO.
J Pediatr. 2017 Dec;191:82-90.e2. doi: 10.1016/j.jpeds.2017.08.055. Epub 2017 Oct 16.
To evaluate fibrosis and fibrosis-related gene expression in the myocardium of pediatric subjects with single ventricle with right ventricular failure.
Real-time quantitative polymerase chain reaction was performed on explanted right ventricular myocardium of pediatric subjects with single ventricle disease and controls with nonfailing heart disease. Subjects were divided into 3 groups: single ventricle failing (right ventricular failure before or after stage I palliation), single ventricle nonfailing (infants listed for primary transplantation with normal right ventricular function), and stage III (Fontan or right ventricular failure after stage III). To evaluate subjects of similar age and right ventricular volume loading, single ventricle disease with failure was compared with single ventricle without failure and stage III was compared with nonfailing right ventricular disease. Histologic fibrosis was assessed in all hearts. Mann-Whitney tests were performed to identify differences in gene expression.
Collagen (Col1α, Col3) expression is decreased in single ventricle congenital heart disease with failure compared with nonfailing single ventricle congenital heart disease (P = .019 and P = .035, respectively), and is equivalent in stage III compared with nonfailing right ventricular heart disease. Tissue inhibitors of metalloproteinase (TIMP-1, TIMP-3, and TIMP-4) are downregulated in stage III compared with nonfailing right ventricular heart disease (P = .0047, P = .013 and P = .013, respectively). Matrix metalloproteinases (MMP-2, MMP-9) are similar between nonfailing single ventricular heart disease and failing single ventricular heart disease, and between stage III heart disease and nonfailing right ventricular heart disease. There is no difference in the prevalence of right ventricular fibrosis by histology in subjects with single ventricular failure heart disease with right ventricular failure (18%) compared with those with normal right ventricular function (38%).
Fibrosis is not a primary contributor to right ventricular failure in infants and young children with single ventricular heart disease. Additional studies are required to understand whether antifibrotic therapies are beneficial in this population.
评估右心室衰竭的单心室小儿患者心肌中的纤维化及纤维化相关基因表达。
对患有单心室疾病的小儿患者及无心力衰竭的心脏病对照患者的离体右心室心肌进行实时定量聚合酶链反应。受试者分为3组：单心室衰竭组（I期姑息治疗前后出现右心室衰竭）、单心室无衰竭组（计划进行初次移植且右心室功能正常的婴儿）和III期组（Fontan手术或III期后出现右心室衰竭）。为评估年龄和右心室容量负荷相似的受试者，将有衰竭的单心室疾病与无衰竭的单心室疾病进行比较，并将III期与无衰竭的右心室疾病进行比较。对所有心脏进行组织学纤维化评估。采用曼-惠特尼检验来确定基因表达的差异。
与无衰竭的单心室先天性心脏病相比，有衰竭的单心室先天性心脏病中胶原蛋白（Col1α、Col3）表达降低（分别为P = 0.019和P = 0.035），且III期与无衰竭的右心室心脏病相比表达相当。与无衰竭的右心室心脏病相比，III期金属蛋白酶组织抑制剂（TIMP-1、TIMP-3和TIMP-4）表达下调（分别为P = 0.0047、P = 0.013和P = 0.013）。无衰竭的单心室心脏病与有衰竭的单心室心脏病之间，以及III期心脏病与无衰竭的右心室心脏病之间，基质金属蛋白酶（MMP-2、MMP-9）相似。右心室衰竭的单心室衰竭性心脏病患者与右心室功能正常的患者相比，右心室纤维化的组织学患病率无差异（分别为18%和38%）。
纤维化并非婴幼儿单心室心脏病右心室衰竭的主要原因。需要进一步研究以了解抗纤维化疗法对该人群是否有益。
