Division of Cardiovascular Medicine, Vanderbilt Heart and Vascular Institute, Vanderbilt University Medical Center, Nashville, TN.
Circ Res. 2022 May 27;130(11):1698-1722. doi: 10.1161/CIRCRESAHA.122.319835. Epub 2022 May 26.
There is increasing evidence regarding the prevalence of genetic cardiomyopathies, for which arrhythmias may be the first presentation. Ventricular and atrial arrhythmias presenting in the absence of known myocardial disease are often labelled as idiopathic, or lone. While ventricular arrhythmias are well-recognized as presentation for arrhythmogenic cardiomyopathy in the right ventricle, the scope of arrhythmogenic cardiomyopathy has broadened to include those with dominant left ventricular involvement, usually with a phenotype of dilated cardiomyopathy. In addition, careful evaluation for genetic cardiomyopathy is also warranted for patients presenting with frequent premature ventricular contractions, conduction system disease, and early onset atrial fibrillation, in which most detected genes are in the cardiomyopathy panels. Sudden death can occur early in the course of these genetic cardiomyopathies, for which risk is not adequately tracked by left ventricular ejection fraction. Only a few of the cardiomyopathy genotypes implicated in early sudden death are recognized in current indications for implantable cardioverter defibrillators which otherwise rely upon a left ventricular ejection fraction ≤0.35 in dilated cardiomyopathy. The genetic diagnoses impact other aspects of clinical management such as exercise prescription and pharmacological therapy of arrhythmias, and new therapies are coming into clinical investigation for specific genetic cardiomyopathies. The expansion of available genetic information and implications raises new challenges for genetic counseling, particularly with the family member who has no evidence of a cardiomyopathy phenotype and may face a potentially negative impact of a genetic diagnosis. Discussions of risk for both probands and relatives need to be tailored to their numeric literacy during shared decision-making. For patients presenting with arrhythmias or cardiomyopathy, extension of genetic testing and its implications will enable cascade screening, intervention to change the trajectory for specific genotype-phenotype profiles, and enable further development and evaluation of emerging targeted therapies.
越来越多的证据表明遗传性心肌病的流行，心律失常可能是其首发表现。在没有已知心肌疾病的情况下出现的室性和房性心律失常通常被标记为特发性或孤立性。虽然室性心律失常被认为是右心室致心律失常性心肌病的表现，但致心律失常性心肌病的范围已经扩大到包括那些主要累及左心室的患者，通常表现为扩张型心肌病的表型。此外，对于频繁出现室性早搏、传导系统疾病和早期心房颤动的患者，也需要仔细评估是否存在遗传性心肌病，因为大多数检测到的基因都在心肌病基因检测面板中。这些遗传性心肌病在早期就可能发生猝死，而左心室射血分数并不能充分跟踪这种风险。只有少数与早期猝死相关的心肌病基因型在目前植入式心脏复律除颤器的适应证中得到认可，而植入式心脏复律除颤器的适应证通常依赖于扩张型心肌病的左心室射血分数≤0.35。遗传诊断会影响其他临床管理方面，如运动处方和心律失常的药物治疗，并且针对特定遗传性心肌病的新疗法正在进入临床研究。可用遗传信息的扩展和影响给遗传咨询带来了新的挑战，特别是对于那些没有心肌病表型证据且可能面临遗传诊断潜在负面影响的家庭成员。在共同决策过程中，需要根据其数字素养来讨论先证者和亲属的风险。对于出现心律失常或心肌病的患者，扩展遗传检测及其影响将能够进行级联筛查、改变特定基因型-表型谱的干预措施，并能够进一步开发和评估新兴的靶向治疗。
