Stay Up to Date! Like us on Facebook  and Twitter  for the latest news and announcements    

Issues Affecting the Heart

Mitochondrial disease is associated with several types of myopathic heart disease including dilated cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular non-compaction (Scaglia, 2004; Towbin, 2006; Yaplito-Lee, 2007). Cardiac arrhythmias also occur though less commonly. Heart block is a classic complication of Kearns-Sayre syndrome, often requiring placement of pacemaker. Wolff-Parkinson-White syndrome is also described in several maternally-inherited disorders (Towbin, 2006).

Symptoms relate to heart failure or dysrhythmias with sudden death occurring as a terminal event (Majamma-Voltti, 2006; Okajima,1998).

While impairment of cardiac muscle or of cardiac rhythm can result directly from abnormal mitochondrial function associated with known molecular mutations or defects in respiratory chain function, a lack of availability of substrate may also contribute to a cardiac energy deficit. While both carbohydrate and fat serve as substrate for oxidative phosphorylation, it is ß-oxidation of fatty acids that is the largest source of energy. Primary disorders of long chain fatty acid oxidation including very long chain acyl CoA dehydrogenase (VLCAD) deficiency and long chain hydroxyacyl CoA dehydrogenase (LCHAD) deficiency are known to be associated with cardiomyopathy (Rinaldo, 2002), as are transport defects which interfere with the transport of long chain fatty acids into the mitochondrion (e.g., carnitine uptake defect, carnitine palmitoyltransferase deficiency) (Rinaldo, 2002). In primary disorders of oxidative phosphorylation, secondary dysfunction of fatty acid oxidation can occur as well (Bennett, 1993; Hagenfeldt, 1998; Enns, 2000).

Finally, autonomic dysfunction can be prominent in mitochondrial disease (Zelnik, 1996; Axelrod, 2006) can be associated with tachycardia and bradycardia with or without appreciated trigger factors, systemic hypotension and hypertension (Johns, 1995), and pulmonary hypertension. Associated symptoms can include dizziness and/or syncope, palpitations, shortness of breath, and acrocyanosis.


Axelrod FB, Chelimsky G, Weese-Mayer DE. Pediatric autonomic disorders. Pediatrics 2006;118:309-21.

Bennett MJ, Sherwood WG, Gibson KM, Burlina AB. Secondary inhibition of multiple NAD-requiring dehydogenases in respiratory complex I deficiency: Possible metabolic markers for the primary defect. J Inher Metab Dis 1993;16:560-62.

Bonnet D, Martin D, de Lonlay P, et al. Arrhythmias and conduction defects as presenting symptoms of fatty acid oxidation disorders in children. Circulation 1999;100: 2248-53.

Enns GM, Bennett MJ, Hoppel CL, et al. Mitochondrial respiratory chain complex I deficiency with clinical and biochemical features of long chain 3-hydoxyacyl-coenzyme A dehydrogenase deficiency. J Pediatr 2000;136:251-4.

Finsterer J, Stollberger C, Blazek G, et al. Cardiac involvement over 10 years in myotonic and Becker muscular dystrophy and mitochondrial disorder. Internat J Cardiol 2007;119:176-84.

Hagenfeldt L. Compromised fatty acid oxidation in mitochondrial disorders. J Inher Metab Dis 1998;21(5):613-7.

Johns D. Mitochondrial DNA and disease. New Engl J Med 1995;333:638-44.

Letsas KP, Efremidis M, Pappas LK, et al. Pathophysiology and management of syncope in Kearns-Sayre syndrome. Am Heart Hosp J 2006;4:301-2.

Majamma-Voltti KAM, Winqvist S, Remes AM, et al. A three-year clinical follow-up of adult patients with 3243A>G in mitochondrial DNA. Neurology 2006;66:1470-5.

McFarland R, Taylor RW, Turnbull DM. Mitochondrial disease - Its impact, etiology and pathology. Curr Topics Dev Biol 2007;77:113-55.

Okajima Y, Tanabe Y, Takayanagi M, Aotsuka H. A follow-up study of myocardial involvement in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). Heart 1998;80(3):292-5.

Rinaldo P, Matern D, Bennett MJ. Fatty acid oxidation disorders. Annual Rev Physiol 2002;64:477-502.

Scaglia F, Towbin JA, Craigen WJ, et al. Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics 2004;114:925-31.

Towbin J. Mitochondrial cardiology. In Mitochondrial Medicine. DiMauro S, Hirano M, Schon EA, eds. Informa Healthcare, Abingdon, 2006. Pg 75-104.

Yaplito-Lee J, Weintraub R, Jamsen K, et al. Cardiac manifestations in oxidative phosphorylation disorders of childhood. J Pediatr 2007;150(4):407-11.

Zelnik N, Axelrod FB, Leschinsky E, et al. Mitochondrial encephalomyopathies presenting with features of autonomic and visceral dysfunction. Pediatr Neurol 1996;14:251-4.

Page Security: