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. 2022 Oct 11;80(15):1431-1443.
doi: 10.1016/j.jacc.2022.04.067.

Impediments to Heart Transplantation in Adults With MELASMT-TL1:m.3243A>G Cardiomyopathy

Alessandro Di Toro  1 , Mario Urtis  2 , Nupoor Narula  3 , Lorenzo Giuliani  1 , Maurizia Grasso  1 , Michele Pasotti  4 , Carlo Pellegrini  5 , Alessandra Serio  1 , Andrea Pilotto  1 , Elena Antoniazzi  6 , Teresa Rampino  7 , Lorenzo Magrassi  8 , Adele Valentini  9 , Anna Cavallini  10 , Laura Scelsi  11 , Stefano Ghio  11 , Massimo Abelli  12 , Iacopo Olivotto  13 , Maurizio Porcu  14 , Antonello Gavazzi  15 , Takahide Kodama  16 , Eloisa Arbustini  17
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Free article

Impediments to Heart Transplantation in Adults With MELASMT-TL1:m.3243A>G Cardiomyopathy

Alessandro Di Toro et al. J Am Coll Cardiol. .
Free article

Abstract

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 MELASMT-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 MELASMT-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.

Keywords: MELAS; MT-TL1:m.3243A>G; heart transplantation; mitochondrial cardiomyopathy.

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Conflict of interest statement

Funding Support and Author Disclosures The study was supported by continuous funds on cardiomyopathies and heart transplantation from the Ministry of Health to the IRCCS Foundation Policlinico San Matteo by project numbers 888-rcr2017i-71 and RCR-2019-23669116_001 CV-PREVITAL (Genetic Section). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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