Background

The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results.

Objectives

We analyzed factors preventing HTx in consecutive adult patients with MELAS^{MT-TL1:m.3243A>G} cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center.

Methods

The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives.

Results

The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis.

Conclusions

High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELAS^{MT-TL1:m.3243A>G} patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.

中文翻译：

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MELASMT-TL1:m.3243A>G 型心肌病成人心脏移植的障碍

背景

心脏通常涉及由线粒体 DNA 的MT-TL1 m.3243A>G 突变引起的母系遗传性线粒体肌病、脑病、乳酸性酸中毒和中风样发作 (MELAS) 综合征。心脏移植（HTx）是有争议的，并且很少有结果相互矛盾的。

目标

我们分析了过去 23 年在我们的 HTx 转诊中心诊断和随访的MELAS ^{MT-TL1 :m.3243A>G型心肌病}连续成年患者中阻止 HTx 的因素。

方法

该系列由 14 名不相关的成年先证者组成，他们在 1998 年至 2021 年期间被转诊进行心肌病评估。在转诊前没有人被怀疑诊断为 MELAS。所有患者都接受了临床和遗传访问和咨询、线粒体 DNA 测序、心血管检查（包括 10 名右心导管和心内膜心肌活检）、多学科评估和生化检查。家庭筛查确定了 2 名受影响的亲属。

结果

心脏表型的特点是肥大、同心、非梗阻性心肌病，通常演变成扩张型心肌病样表型。在 14 名先证者中，7 名是 HTx 的潜在候选者，2 名心脏和肾脏 Tx 的潜在候选人，1 名在 3 年的活跃 HTx 名单上。10 名先证者均未接受 HTx。目前正在为 HTx 评估一个。所有人都患有糖尿病、听力损失和肌病，10 人患有慢性肾病和进行性脑肌病。在随访期间，10 人在基因诊断后 5 年内死于与多器官衰竭相关的心力衰竭。

结论

^{MELAS MT-TL1 :m.3243A>G}患者中风样发作、慢性肾脏疾病和消耗性肌病的高风险阻止了 HTx 计划的激活。因此，在这种综合征背景下对他们的心肌病的管理仍然是一个未满足的临床需求。