Electrophysiologic Manifestations of Mitochondrial Crisis

Abstract

<h3>Background</h3> Mitochondrial disorders are unique genetic conditions characterized by abnormal energy metabolism resulting in inadequate adenosine triphosphate (ATP) supply, which in certain situations may result in mitochondrial crisis. Such crisis can manifest with life-threatening cardiac repolarization abnormalities, ventricular arrhythmias, and acute left ventricular (LV) dysfunction. In this case series, we assessed arrhythmia burden and effectiveness of biochemical therapies rather than antiarrhythmics in the treatment of rhythm disturbances during crisis. <h3>Methods</h3> Patients with mitochondrial disorder who developed crisis were identified from the University of Texas Health Science Center Mitochondrial Disorder Database. The cardiac and electrophysiologic characteristics of these crises were analyzed. <h3>Results</h3> Seven of 162 patients (4%) were identified as having mitochondrial crisis. Mean age was 11, with 3 females (43%) and 4 males (57%). Fifty-seven percent (4/7) had structural heart disease, including left ventricular (LV) noncompaction and septal defects. Additional findings include dysautonomy (28% [2/ 7]), preexcitation syndrome (14% [1/7]), and preexisting long QT with mean QTc of 479ms (43% [3/7]). Two patients (28%) had acute development of severe LV systolic dysfunction, profound repolarization abnormalities on ECG (max QTc 640 ms), and ventricular arrhythmias. These patients had complete recovery of LV function and resolution of arrhythmia burden with biochemical therapies, including arginine and carnitine, without anti-arrhythmic therapy. Five patients (71%) died during their crisis. <h3>Conclusions</h3> Although the incidence of crisis in patients with mitochondrial disorders is low, these patients have high mortality. This case series illustrates the complexity of mitochondrial dysfunction and its association with acute LV dysfunction, arrhythmias, and death. These patients may have preexisting ion channelopathies or substrate for cardiac arrhythmias and hence are vulnerable to lethal arrhythmias during crisis. Further exploration into the electrophysiologic properties of mitochondrial disorders may help elucidate the exact mechanism of arrhythmias and may perhaps improve treatment strategies.