Division of Cardiology, Department of Pediatrics, University of Colorado Denver, Aurora, Colorado.
Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, Colorado.
Am J Physiol Heart Circ Physiol. 2020 Apr 1;318(4):H947-H965. doi: 10.1152/ajpheart.00518.2019. Epub 2020 Feb 28.
Because of remarkable surgical and medical advances over the past several decades, there are growing numbers of infants and children living with single ventricle congenital heart disease (SV), where there is only one functional cardiac pumping chamber. Nevertheless, cardiac dysfunction (and ultimately heart failure) is a common complication in the SV population, and pharmacological heart failure therapies have largely been ineffective in mitigating the need for heart transplantation. Given that there are several inherent risk factors for ventricular dysfunction in the setting of SV in addition to probable differences in molecular adaptations to heart failure between children and adults, it is perhaps not surprising that extrapolated adult heart failure medications have had limited benefit in children with SV heart failure. Further investigations into the molecular mechanisms involved in pediatric SV heart failure may assist with risk stratification as well as development of targeted, efficacious therapies specific to this patient population. In this review, we present a brief overview of SV anatomy and physiology, with a focus on patients with a single morphological right ventricle requiring staged surgical palliation. Additionally, we discuss outcomes in the current era, risk factors associated with the progression to heart failure, present state of knowledge regarding molecular alterations in end-stage SV heart failure, and current therapeutic interventions. Potential avenues for improving SV outcomes, including identification of biomarkers of heart failure progression, implications of personalized medicine and stem cell-derived therapies, and applications of novel models of SV disease, are proposed as future directions.
由于过去几十年中显著的外科和医学进步，越来越多的婴儿和儿童患有单心室先天性心脏病 (SV)，即只有一个功能性心脏泵室。然而，心脏功能障碍（最终导致心力衰竭）是 SV 人群中的常见并发症，心力衰竭的药理学治疗在很大程度上无法减轻心脏移植的需求。鉴于 SV 患者存在多种潜在的心室功能障碍风险因素，而且儿童和成人对心力衰竭的分子适应可能存在差异，因此推断成人心力衰竭药物对 SV 心力衰竭儿童的益处有限也就不足为奇了。进一步研究儿科 SV 心力衰竭所涉及的分子机制可能有助于进行风险分层，并为这一特定患者群体开发靶向、有效的治疗方法。在这篇综述中，我们简要介绍了 SV 的解剖结构和生理学，重点介绍了需要分阶段手术姑息治疗的单一形态右心室患者。此外，我们还讨论了当前的治疗效果、与心力衰竭进展相关的风险因素、SV 心力衰竭终末期分子改变的现有知识状态，以及当前的治疗干预措施。提出了一些改善 SV 预后的潜在途径，包括确定心力衰竭进展的生物标志物、个性化医学和干细胞衍生疗法的意义，以及 SV 疾病新型模型的应用，作为未来的发展方向。
