Long-chain
fatty acid oxidation disorders (LC-FAOD) can cause
cardiac hypertrophy and
cardiomyopathy, often presenting in infancy, typically leading to death or heart transplant despite ongoing treatment. Previous data on
triheptanoin treatment of
cardiomyopathy in LC-FAOD suggested a clinical benefit on heart function during acute failure. An additional series of LC-FAOD patients with critical emergencies associated with
cardiomyopathy was treated with
triheptanoin under
emergency treatment or compassionate use protocols. Case reports from 10 patients (8 infants) with moderate or severe
cardiomyopathy associated with LC-FAOD are summarized. The majority of these patients were detected by newborn screening, with follow up confirmatory testing, including mutation analysis; all patients were managed with standard treatment, including medium chain
triglyceride (MCT) oil. While on this regimen, they presented with acute
heart failure requiring hospitalization and cardiac support (ventilation, ECMO, vasopressors) and, in some cases,
resuscitation. The patients discontinued MCT oil and began treatment with
triheptanoin, an
investigational drug.
Triheptanoin is expected to provide anaplerotic metabolites, to replace deficient TCA cycle intermediates and improve effective energy metabolism. Cardiac function was measured by echocardiography and ejection fraction (EF) was assessed. EF was moderately to severely impaired prior to
triheptanoin treatment, ranging from 12-45%. Improvements in EF began between 2 and 21days following initiation of
triheptanoin, and peaked at 33-71%, with 9 of 10 patients achieving EF in the normal range. Continued treatment was associated with longer-term stabilization of clinical signs of
cardiomyopathy. The most common adverse event observed was gastrointestinal distress. Of the 10 patients, 7 have continued on treatment, 1 elected to discontinue due to tolerability issues, and 2 patients died from other causes. Two of the case histories illustrate that
cardiomyopathy may also develop later in childhood and/or persist into adulthood. Overall, the presented cases suggest a
therapeutic effect of
triheptanoin in the management of acute
cardiomyopathy associated with LC-FAOD.