PO68 Against All (Mitochondrial) Odds: Unexpected Improvement with Guideline-Directed Heart Failure Medical Therapy: A Case Report

Introduction Maternally Inherited Diabetes and Deafness (MIDD) is a rare mitochondrial disorder characterized by the combination of diabetes mellitus and sensorineural hearing loss, with m.3243A>G mutation and often associated with cardiovascular disease. The specific heart failure treatment in this specific group of patients is unknown. Case Presentation A 39-year-old male was admitted to the Cardiology ward due to orthopnoea, reduced tolerance to exercise, unexpected rapid weight gain and bi-malleolar and oedema. His past medical history was remarkable for Maternally Inherited Diabetes and Deafness (MIDD) with an m.3243A>G variant, presenting with progressive sensorineural hearing loss, mitochondrial retinal dystrophy and having had received a kidney transplant 5 years prior to admission. On physical examination, the patient had signs of congestive heart failure (HF). Intravenous diuretic was started with an improvement of signs and symptoms of HF. The electrocardiogram revealed sinus rhythm with intermittent left bundle branch block (QRS∼110-130ms) and normal PQ interval. On transthoracic echocardiogram (TTE) there was marked left ventricular (LV) “hypertrophy”, severely reduced LV ejection fraction (LVEF 28%) and restrictive physiology (E/A 4.3, E/e’ ratio 33). The cardiac magnetic resonance (CMR) demonstrated “patchy” mid-wall linear late gadolinium enhancement (LGE) on the basal septum and several fibrotic foci involving all LV walls. Global T1 mapping values were markedly reduced (939 ± 67ms; institutional lower cut-off: 980ms), which could suggest the accumulation of free acid metabolites or iron overload consequent to mitochondrial dysfunction. The coronary CT-angiography excluded coronary artery disease. During the hospital stay, the patient was started on conventional guideline directed medical therapy (GDMT) for HF with reduced LVEF, with the exception of mineralocorticoid receptor antagonists, due to persistent hyperkalaemia. After multidisciplinary discussion, given the lack of evidence of conventional GDMT on this specific HF aetiology and the high risk of sudden cardiac death (SCD) reported in the literature in mitochondrial cardiomyopathy, it was decided in favour of a tranvenous implantable cardioverter-defibrillator (ICD) as primary prevention of SCD. At 3 months of GDMT treatment with ramipril 5mg bid, carvedilol 6.25mg bid and dapaglifozin 10mg id, he returned for re-evaluation presenting with: no cardiovascular complaints (NYHA I), cardiopulmonary exercise testing with reduced pVO2 (16,4mL/Kg/min) on maximal effort (QR 1,17), partially recovered LVEF (40%) and improved diastolic function (E/A 1,3, E/e’ ratio 14). Conclusion We here present the case of a young patient with mitochondrial disease and severe cardiac disease, most likely due to infiltrative cardiomyopathy. This case highlights that the m.3243A>G mutation often associates with cardiovascular disease, thus emphasizing the importance of phenotyping with cardiac imaging (TTE and CMR). Moreover, the improvement of functional status and LV function in this case suggests a potential role of conventional HF GDMT, although SCD risk stratification and decision for ICD should always be individualized in rare specific aetiologies.