Expanded-access use of elamipretide in a critically ill patient with Barth syndrome

Abstract

Purpose: Barth syndrome (BTHS; OMIM #302060) is a rare disease characterized by cardiolipin abnormalities and cardiomyopathy, intermittent neutropenia and skeletal myopathy among other defects. Elamipretide is an investigational drug that binds to cardiolipin, resulting in improved membrane stability, cellular respiration, and adenosine triphosphate production. This case report seeks to provide guidance to clinicians for the effective use of elamipretide when managing BTHS patients. Methods: Here, we report an 11-month-old male requiring cardiopulmonary resuscitation and intubation on initial presentation. Echocardiogram showed a dilated left ventricle (LV) with severely diminished systolic LV function. The patient was placed on venoarterial extracorporeal membrane oxygenation (ECMO) due to a low cardiac output state. Within about two weeks of hospitalization, a diagnosis of BTHS was confirmed on rapid exome sequencing; daily elamipretide therapy (5 mg) was initiated. Results: The patient was decannulated from ECMO. Due to failing extubation, a Berlin Heart EXCOR left ventricular assist device (LVAD) was placed on hospital-day 29. Approximately five months later, echocardiogram demonstrated a marked improvement in LVEF (18% to 54%), with cardiac catheterization during pause of LVAD support indicating hemodynamic parameters favorable for LVAD explantation. He underwent successful LVAD explantation and was removed from the cardiac transplant list. The patient was discharged from the hospital and has remained stable on daily elamipretide therapy. Conclusion: In previous studies, elamipretide therapy has demonstrated normalization of mitochondrial function alongside improvement in LV function. Observations made in our case support these findings and emphasize the need for readily available, targeted therapies in BTHS patients.

Keywords

• Barth syndrome
• Cardiolipin
• Cardiomyopathy
• Elamipretide
• Mitochondria