Di Toro Alessandro, Urtis Mario, Narula Nupoor, Giuliani Lorenzo, Grasso Maurizia, Pasotti Michele, Pellegrini Carlo, Serio Alessandra, Pilotto Andrea, Antoniazzi Elena, Rampino Teresa, Magrassi Lorenzo, Valentini Adele, Cavallini Anna, Scelsi Laura, Ghio Stefano, Abelli Massimo, Olivotto Iacopo, Porcu Maurizio, Gavazzi Antonello, Kodama Takahide, Arbustini Eloisa
Transplant Research Area and Centre for Inherited Cardiovascular Diseases, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Transplant Research Area and Centre for Inherited Cardiovascular Diseases, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.
J Am Coll Cardiol. 2022 Oct 11;80(15):1431-1443. doi: 10.1016/j.jacc.2022.04.067.
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.
We analyzed factors preventing HTx in consecutive adult patients with MELAS cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center.
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.
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.
High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELAS patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.
心脏通常会受到线粒体DNA的MT-TL1 m.3243A>G突变所导致的母系遗传性线粒体肌病、脑病、乳酸性酸中毒和卒中样发作（MELAS）综合征的影响。心脏移植（HTx）存在争议，且很少进行，结果也相互矛盾。
我们分析了在过去23年里于我们的心脏移植转诊中心确诊并随访的连续性成年MELAS心肌病患者中，阻碍心脏移植的因素。
该系列包括14名无关的成年先证者，他们于1998年至2021年被转诊以评估心肌病。转诊前均未怀疑患有MELAS。所有患者均接受了临床和基因问诊与咨询、线粒体DNA测序、心血管检查（包括10例患者进行了右心导管检查和心内膜心肌活检）、多学科评估以及生化检测。家族筛查发现了2名受影响的亲属。
心脏表型的特征为肥厚性、向心性、非梗阻性心肌病，常演变为扩张型心肌病样表型。14名先证者中，7名是心脏移植的潜在候选者，2名是心脏和肾脏移植的候选者，1名在心脏移植活动名单上待了3年。10名先证者均未接受心脏移植。1名目前正在接受心脏移植评估。所有人都患有糖尿病、听力丧失和肌病，10人患有慢性肾病和进行性脑病。在随访期间，10人在基因诊断后的5年内死于与多器官衰竭相关的心力衰竭。
MELAS患者发生卒中样发作、慢性肾病和进行性肌病的高风险阻碍了心脏移植计划的启动。因此，在这种综合征背景下对其心肌病的管理仍然是一项未满足的临床需求。
