Abstract 199: Subclinical Myocardial Ischemia Without LV Hypertrophy in Friedreich’s Ataxia
Background: Heart failure mortality is high in patients with Friedreich’s Ataxia (FA), a genetic disorder resulting in iron accumulation within cardiomyocyte mitochondria. Due to limited mobility, cardiomyopathy in FA patients may not be detected until myocardial disease is advanced. We hypothesized that abnormal myocardial perfusion represents an early manifestation of cardiomyopathy, and can be detected with vasodilator stress cardiac magnetic resonance (CMR).
Methods: Eleven patients with genotype-confirmed FA age 33±8 years and 12 age-matched healthy controls underwent CMR with adenosine stress. Myocardial perfusion reserve index (MPRI) was quantified using the normalized upslope of myocardial signal enhancement during vasodilator stress versus rest. Left ventricular (LV) mass was computed from contiguous short-axis cine images. Myocardial T2* measurement was performed for iron quantification.
Results: All but two FA patients were wheelchair-bound. None had hypertension or were on cardioactive medications, and none were on CoQ10 analogs or chelation therapy. LV mass and ejection fraction averaged 100±19g and 61±18%, respectively, indicating preserved systolic function and absence of significant hypertrophy. Myocardial iron overload could not be detected (T2* 29±4 ms). Quantification of MPRI revealed significantly lower endocardial to epicardial perfusion reserve ratio in patients vs. controls (0.79 +/− 0.07 vs. 0.97 +/− 0.06, p=0.03).
Conclusion: Patients with Friedreich’s ataxia have measurable abnormalities in myocardial perfusion reserve index in the absence of overt hypertrophy, LV dysfunction or iron overload. This microvascular abnormality may represent a novel therapeutic target for FA-associated cardiomyopathy. Further investigation in this population and other cardiomyopathy patients with mitochondrial dysfunction is warranted.