title: Triheptanoin treatment in patients with pediatric cardiomyopathy associated with long chain-fatty acid oxidation disorders.
abstract: 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.
authors: Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. Electronic address: vockleyg@upmc.edu.
authors: J
authors: J
authors: Vockley
authors: Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
authors: J
authors: J
authors: Charrow
authors: Cooper University, Camden, NJ, USA.
authors: J
authors: J
authors: Ganesh
authors: Sutter Medical Center, Sacramento, CA, USA.
authors: M
authors: M
authors: Eswara
authors: Mt. Sinai School of Medicine, New York, NY, USA.
authors: G A
authors: GA
authors: Diaz
authors: Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors: E
authors: E
authors: McCracken
authors: Children's Hospital of Michigan, Detroit, MI, USA.
authors: R
authors: R
authors: Conway
authors: Lucile Packard Children's Hospital Stanford, Palo Alto, CA, USA.
authors: G M
authors: GM
authors: Enns
authors: Children's Hospital of Orange County, Orange, CA, USA.
authors: J
authors: J
authors: Starr
authors: Children's Hospital of Orange County, Orange, CA, USA.
authors: R
authors: R
authors: Wang
authors: Children's Hospital of Orange County, Orange, CA, USA.
authors: J E
authors: JE
authors: Abdenur
authors: Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors: J
authors: J
authors: Sanchez-de-Toledo
authors: Ultragenyx Pharmaceutical, Inc., Novato, CA, USA.
authors: D L
authors: DL
authors: Marsden
mesh_terms: D000293:Adolescent; D009202:Cardiomyopathies / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D014280:Triglycerides / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D005227:Fatty Acids; D014280:Triglycerides; C531010:triheptanoin
keywords: Cardiomyopathy; Fatty acid oxidation disorders; Metabolic disorders; Triheptanoin