A 35-year-old woman (body mass index, 16 kg/m 2 ; height, 140 cm) presented to the emergency ward with severe dyspnea of acute onset. The medical history was noteworthy for bilateral hypacusis treated with a hearing aid.On admission, the laboratory results revealed an N-terminal prohormone of brain natriuretic peptide level of 10 219 ng/L (normal Ͻ200 ng/L). Thoracic CT scan excluded pulmonary embolism but showed cardiomegaly with pericardial and bilateral pleural effusion suggesting the presence of acute heart failure. Cardiac MRI (CMR) demonstrated a severely reduced left ventricular ejection fraction (LVEF, 13%) and severe right ventricular dysfunction ( Figure 1A and 1B, baseline); LV mass index was normal. Late gadolinium enhancement images demonstrated extensive subepicardial lesions in inferior and lateral LV segments ( Figure 1C, baseline). The angiogram excluded a coronary pathology, and myocardial histology was without histological signs of infiltrative or active inflammatory disease. The ECG was noteworthy for a shortened PQ interval, but supraventricular tachycardia was not revealed during long-term ECG monitoring. Otherwise, the patient showed a hyperglycemic fasting glucose level (7.5 mmol/L; normal Ͻ5.6 mmol/L), and, whereas lactate level was normal at rest (2 mmol/L; normal Ͻ2.4 mmol/L), a rapid increase to 4.3 mmol/L was noteworthy after 150 seconds of bicycle exercise at 35 W. Cerebral MRI showed cerebellar atrophy (Figure 2) in the absence of a clinically relevant neurological disorder, and ophthalmologic examination revealed bilateral ocular maculopathy.With standard heart failure therapy including low-dose -blockade, angiotensin-converting enzyme inhibition, aldosterone blockade, and loop diuretics, the patient recovered to New York Heart Association class II; in parallel, the NTproBNP-level decreased to 391 ng/L. After 18 months, CMR showed significant improvement of systolic biventricular function (LVEF, 48%; minor right ventricular dysfunction) ( Figure 1D and 1E), whereas volume and pattern of the myocardial lesions remained unchanged ( Figure 1F). Short stature, bilateral hypacusis, retinal dystrophy, cerebellar atrophy, cardiomyopathy with conduction abnormality, hyperglycemia, and a history of hypacusis and ocular maculopathy in the maternal family suggested mitochondrial disorder. Genetic analysis revealed the presence of A3243G mutation in 30Ϯ10% of the mitochondrial DNA extracted from the patient's leukocytes. This mutation occurs in 80% of individuals with MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes), which is observed with a prevalence of 13 in 100 000 in the European population. 1 The clinical presentation of MELAS syndrome is variable, with severe forms showing myopathy, ophthalmoplegia, stroke-like episodes, and left ventricular hypertrophy (LVH), whereas mild forms may be limited to adult-onset diabetes mellitus or neurosensory hearing loss. 2 The heterogeneity of the clinical phenotype is based on the variable burden of the mutation i...