Heart transplantation for mitochondrial cardiomyopathy and associated metabolic syndromes: Case series and systematic literature review

Abstract

Introduction: Mitochondrial diseases (MtDs) are a diverse group of inherited metabolic disorders that frequently involve the heart, leading to progressive cardiomyopathy and heart failure. In advanced stages, transplantation may be the only life-saving option, though its role remains poorly defined due to the rarity and complexity of these syndromes. This review examines the outcomes of heart transplantation in patients with MtD and reports two additional cases from our centre. These represent the first known transplants for maternally- inherited diabetes and deafness (MIDD) and for a homoplasmic m.4300 mutation syndrome.

Methodology: We systematically searched Medline, Embase, Cochrane Library, and Web of Science from inception to May 2025 using MeSH and free-text terms for heart transplantation and mitochondrial disease. Studies with original patient data and genetically or clinically confirmed mitochondrial disease were included. Screening, synthesis, and quality appraisal followed PRISMA 2020 and Joanna Briggs Institute (JBI) guidelines for case reports and series.

Results: Sixteen publications describing 27 patients met inclusion criteria. Most were single- case reports or small series, predominantly involving MELAS, Kearns–Sayre, or Friedreich's ataxia. Short-term post-transplant survival was excellent (100%, 95% CI 86–100) at median two-year follow-up. Neurological or metabolic complications, including stroke-like episodes, occurred in approximately 10% of cases. Our two patients with MIDD and homoplasmic m.4300 mutation achieved stable graft function and complete neurological recovery at 12 and 24 months, respectively.

Conclusion: Heart transplantation can be effective for carefully selected patients with mitochondrial cardiomyopathy. Successful outcomes require meticulous perioperative metabolic management, neurological monitoring, and multidisciplinary coordination. Broader, collaborative studies are needed to refine patient selection criteria and establish structured long-term follow-up protocols.