Advances in the Understanding of the Genetic Determinants of Congenital Heart Disease and Their Impact on Clinical Outcomes.
Advances in the Understanding of the Genetic Determinants of Congenital Heart Disease and Their Impact on Clinical Outcomes.
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DOI：
10.1161/jaha.117.006906
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发表时间：
2018-03-09
影响因子：
5.4
通讯作者：
Miller TA
中科院分区：
文献类型：
--
作者：
Russell MW;Chung WK;Kaltman JR;Miller TA
先天性心脏缺陷（CHD）是最常见的出生缺陷类型，占活产婴儿的% 1% 1，如果包括二叶式主动脉瓣等轻微心脏异常，则患病率可能高达2%至3%。2外科手术、围手术期护理和导管介入治疗的进步显著提高了生存率，但最复杂的心脏缺陷的早期死亡率仍高达20%。3此外，许多幸存者需要长期的医疗护理，在认知、行为、注意力和运动表现方面存在功能缺陷，这限制了他们的教育和就业机会，降低了他们的生活质量。随着冠心病患者生存率的提高，人们越来越重视了解结局的变化，并改善短期和长期结局，包括但不限于生存率。虽然最近的努力，以优化和标准化的临床实践和围手术期护理，导致了小的增量改善，他们没有导致临床结果的重大进展。越来越多的结果研究的重点是了解个体患者之间的差异（包括遗传因素和临床护理或临床过程中的特定变化），预测或确定临床结果。最近，更好地理解和改善临床结果的努力得到了补充措施的帮助，以确定CHD的原因。高通量DNA测序成本的下降，生物信息学分析的进步，以及对大量CHD患者的收集和遗传特征的投资，迅速推进了我们对CHD遗传结构的理解。正在出现的是对潜在遗传因素如何影响特定测量的临床结果以及在评估干预措施和新治疗方法的有效性时考虑这些因素的重要性的更好理解。在这篇综述中，我们将研究在特定遗传病因背景下冠心病患者的临床结局，如生存率、认知和行为、生长和心功能。
Congenital heart defects (CHDs) are the most common type of birth defect occurring in% 1% of live births1 and, if minor cardiac abnormalities such as bicuspid aortic valve are included, then the prevalence may be as high as 2% to 3%. 2 Advances in surgical and perioperative care and catheter-based interventions have dramatically improved survival, yet there continues to be% 20% early mortality for the most complex cardiac defects. 3 Furthermore, many of the survivors need long-term medical care and have functional deficits in cognition, behavior, attention, and exercise performance that limit educational and employment opportunities and reduce their quality of life. 4 As survival for patients with CHD has improved, there has been an increased emphasis on understanding variation in outcome and in improving shortand long-term outcomes, which include but are not limited to survival. While recent efforts to optimize and standardize clinical practice and perioperative care have resulted in small incremental improvements, they have not led to major advances in clinical outcomes. Increasingly, the focus of outcomes research is on understanding the differences between individual patients (including genetic factors and specific variations in clinical care or clinical course) that predict or determine clinical outcomes. Recently, the effort to better understand and improve clinical outcomes has been aided by complementary initiatives to identify the causes of CHD. A fall in the costs of high-throughput DNA sequencing, advances in bioinformatic analyses, and an investment in funding the collection and genetic characterization of large cohorts of patients withCHD has rapidly advanced our understanding of the genetic architecture of CHD. What is emerging is an improved understanding of how underlying genetic factors can influence specific measured clinical outcomes and the importance of considering these factors when assessing the effectiveness of interventions and new treatment approaches. In this review, we will examine clinical outcomes such as survival, cognition and behavior, growth, and cardiac function for patients with CHD in the context of specific genetic etiologies.