786 A case of end-stage mitochondrial cardiomyopathy undergoing heart and kidney transplantation

Abstract

Abstract Male, 46 year old. Family history: brother affected by deafness and repeated episodes of stroke at a young age. Pathological history: history of competitive sporting activity in which he underwent periodic outpatient checks and reported sporadic myalgic episodes. The patient was suffering from bilateral keratoconus. For the purpose of discovering Wolf–Parkinson–White syndrome with the presence of a right antero-septal accessory pathway, he underwent an electrophysiological study (2003) negative for inducible arrhythmias. During a routine checkup, a renal biopsy was performed to search for elevated blood creatinine, which concluded with acute interstitial nephritis (2005), treated ineffectively with steroids and resulted in dialysis-dependent stage V renal failure (2020). Following light tiredness, he underwent an echocardiographic examination (2009) which revealed the presence of dilated heart disease with reduced left ventricular systolic function. He underwent a cardiac MRI which showed diffuse spots of subepicardial late enhancement as a possible post-myocarditis outcome. At subsequent clinical-echocardiographic checks, progressive biventricular dysfunction, and signs of congestive heart failure were highlighted, for which medical therapy was progressively increased and insertion of an implantable cardioverter defibrillator in primary prevention for sudden cardiac death. At the subsequent clinical re-evaluations, there was evidence of progressive bilateral hearing loss. In consideration of the clinical picture and family history, considering the syndromic nature of the polypathologies to be likely, genetic investigation was required for mitochondrial diseases. Mutations 3242 and 3271mt-RNA and 13513 mtND5, frequent in the MELAS Syndrome, were searched in peripheral venous samples and resulted as negative. In 2020 he underwent an orthotopic heart transplant sec. Shamway followed by a kidney transplant from a compatible donor. In order to perform further diagnostic investigations, the explanted heart was sent to the Pathological Anatomy laboratory of the Umberto I Hospital: macroscopic analysis showed foci of fat replacement at the level of the anterior and posterior wall of the right ventricle (Figure); under microscopy, marked myocardial hypertrophy was observed, associated with cytoplasmic vacuolization of the cardiomyocytes, fibro-adipose substitution of the right ventricle, and replacement fibrosis in minute foci in the left ventricular level. A widespread and marked reduction in the enzymatic activity of cytochrome oxidase in cardiomyocytes and mitochondrial proliferation was demonstrated using histo-enzymatic staining, by staining for succinate dehydrogenase, concluding with mitochondrial disease. Mitochondrial diseases represent a challenge not only from the prognostic–therapeutic point of view but, remarkably, also from a diagnostic one: the patient received a correct diagnosis of the pathology that afflicted him, with almost two decades of delay. The integrated and multidisciplinary approach is desirable in order to obtain an early diagnosis.