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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.


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