Binder Christina, Schmid Lena Marie, Kronberger Christina, Poledniczek Michael, Rettl René, Schlein Johanna, Ermolaev Nikita, Ligios Luciana Camuz, Auer-Grumbach Michaela, Hengstenberg Christian, Eslam Roza Badr, Kastner Johannes, Bergler-Klein Jutta, Kammerlander Andreas Anselm, Duca Franz
Department of Internal Medicine, Division of Cardiology, Medical University of Vienna, 1090 Wien, Austria.
Department of Cardiac Surgery, Medical University of Vienna, 1090 Wien, Austria.
J Clin Med. 2024 Dec 23;13(24):7857. doi: 10.3390/jcm13247857.
Variant transthyretin amyloidosis cardiomyopathy (ATTRv-CM) is a rare form of cardiac amyloidosis associated with many possible mutations in the transthyretin gene, presenting as various distinct clinical phenotypes. Among these, the His108Arg mutation is the most prevalent TTR variant in Austria. However, data describing its clinical phenotype are lacking. This study aims to describe the characteristics, clinical manifestations, and outcomes of patients with the His108Arg variant focusing on cardiac involvement, disease progression, response to therapy, and imaging findings. Patients were enrolled from a prospective cardiac amyloidosis registry. The baseline assessment included comprehensive echocardiography, cardiac magnetic resonance imaging, a biomarker analysis, and a clinical evaluation. Patients were followed longitudinally, with outcomes such as arrhythmias, heart failure hospitalizations, and response to disease-targeted therapies recorded. Between March 2012 and June 2024, a total of 20 carriers of the His108Arg variant were identified, with 12 exhibiting clear cardiac involvement and 8 remaining asymptomatic. The median age at diagnosis was 62.3 years with significant heterogeneity in the clinical presentation. Patients with ATTRv-CM had a high prevalence of atrial and ventricular arrhythmias, a reduced left ventricular ejection fraction, and elevated cardiac biomarkers. The majority received specific disease-modifying therapies, with varying tolerance and responses. A longitudinal follow-up indicated frequent arrhythmic events, heart failure exacerbations, and three cases of heart transplantation, underscoring the need for stringent monitoring and individualized management strategies. This study represents a unique, comprehensive analysis of the His108Arg variant in ATTR-CM, highlighting its clinical heterogeneity and significant impact on cardiac function and clinical outcomes.
变异型转甲状腺素蛋白淀粉样变心肌病（ATTRv-CM）是一种罕见的心脏淀粉样变，与转甲状腺素蛋白基因的许多可能突变相关，表现为多种不同的临床表型。其中，His108Arg突变是奥地利最常见的TTR变异体。然而，缺乏描述其临床表型的数据。本研究旨在描述His108Arg变异体患者的特征、临床表现和预后，重点关注心脏受累情况、疾病进展、治疗反应和影像学表现。患者来自前瞻性心脏淀粉样变登记处。基线评估包括全面的超声心动图、心脏磁共振成像、生物标志物分析和临床评估。对患者进行纵向随访，记录心律失常、心力衰竭住院和针对疾病的治疗反应等结果。在2012年3月至2024年6月期间，共确定了20名His108Arg变异体携带者，其中12名表现出明显的心脏受累，8名仍无症状。诊断时的中位年龄为62.3岁，临床表现存在显著异质性。ATTRv-CM患者房性和室性心律失常的患病率较高，左心室射血分数降低，心脏生物标志物升高。大多数患者接受了特定的疾病修饰治疗，耐受性和反应各不相同。纵向随访表明心律失常事件频繁、心力衰竭加重，并有3例心脏移植病例，强调了严格监测和个体化管理策略的必要性。本研究对ATTR-CM中的His108Arg变异体进行了独特而全面的分析，突出了其临床异质性以及对心脏功能和临床结局的重大影响。
