The mitochondrial DNA mutation MT-TL1 m.3243A>G causes maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like events (MELAS) syndrome, which frequently affects the heart. Heart transplantation (HTx) is debatable and has only sometimes been done, with mixed results. In a study of consecutive adult patients with MELASMT-TL1:m.3243A>G cardiomyopathy who were diagnosed and monitored over the course of 23 years in their HTx referral center, researchers examined variables that prevented HTx.

The series comprised 14 adult probands who are not related and were submitted for cardiomyopathy examination between 1998 and 2021. Before being referred, none had a MELAS diagnosis that was suspected. Clinical and genetic counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization & endomyocardial biopsy in 10 patients), multidisciplinary evaluation, & biochemical testing were all performed on all patients. A family screening revealed two afflicted kin.

Hypertrophic, concentric, nonobstructive cardiomyopathy, which frequently progressed into a phenotype similar to dilated cardiomyopathy, was the hallmark of the cardiac phenotype. Of the 14 probands, 7 had HTx eligibility, 2 had heart and kidney Tx, and 1 had been on the active HTx list for 3 years. All ten probands were not treated with HTx. One is now being assessed for HTx. All had diabetes, hearing loss, and myopathy, and 10 also had progressive encephalomyopathy and chronic renal disease. During follow-up, 10 people passed away within 5 years of the genetic diagnosis from heart failure related to multiorgan failure.

Plans for HTx cannot be implemented because of the high risk of stroke-like episodes, chronic renal disease, and wasting myopathy in MELASMT-TL1:m.3243A>G patients. As a result, there was still a clinical need for the therapy of their cardiomyopathy in this syndromic environment.