BACKGROUND The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1m.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 endo-myocardial 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. (C) 2022 by the American College of Cardiology Foundation.
Impediments to Heart Transplantation in Adults With MELASMT-TL1:m.3243A>G Cardiomyopathy
Di Toro, Alessandro;Urtis, Mario;Grasso, Maurizia;Pasotti, Michele;Pellegrini, Carlo;Serio, Alessandra;Antoniazzi, Elena;Magrassi, LorenzoWriting – Review & Editing
;Valentini, Adele;Cavallini, Anna;Ghio, Stefano;Arbustini, Eloisa
2022-01-01
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-TL1m.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 endo-myocardial 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. (C) 2022 by the American College of Cardiology Foundation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
