Long-chain
fatty acid oxidation disorders (LC-FAOD) are a group of
inborn errors of metabolism wherein patients are unable to process long-chain
fatty acids into useable energy in the mitochondria. LC-FAOD commonly affects organ systems with high energy demand, manifesting as hypoketotic
hypoglycemia,
liver dysfunction,
cardiomyopathy,
rhabdomyolysis, and skeletal
myopathy, as well as
peripheral neuropathy and retinopathy in some subtypes. Collectively, LC-FAOD have a high mortality rate, especially in cases of early onset disease, and in the presence of
cardiomyopathy.
Triheptanoin is a synthetic medium-odd chain
triglyceride, produced using a GMP-compliant process, which was designed to replenish mitochondrial metabolic deficits and restore energy homeostasis. Prior to its approval,
triheptanoin was only available through clinical trials or to seriously ill patients as part of an expanded access program (EAP) following physician request. This retrospective study examined the impact of
triheptanoin on cardiovascular parameters, in
critically ill patients who participated in the EAP from February 2013 to January 2018. These patients persisted in critical condition despite receiving standard treatment in highly qualified centers by expert metabolic physicians and dietitians. Physician-completed questionnaires and narrative summaries were used to evaluate the disease presentation and management prior to the trigger event leading to
triheptanoin request and use, and the response to
triheptanoin treatment. Following
triheptanoin initiation, most patients survived the initial trigger event (e.g., severe
urinary tract infection,
pneumonia) and demonstrated improvements in both short-term and long-term LC-FAOD manifestations. In patients with
cardiomyopathy, stabilization or improvement from pretreatment levels was reported in left ventricular ejection fraction and left ventricular mass, in particular, all infants with
cardiomyopathy showed improvement in cardiac function during
triheptanoin therapy.
Triheptanoin therapy was generally well tolerated. The study results are consistent with the existing positive benefit/risk profile of
triheptanoin and reflect the effect of
triheptanoin improving cardiac function in patients experiencing severe episodes of metabolic decompensation despite standard
therapy.