Microvascular dysfunction contributes to atrial fibrillation in hypertrophic cardiomyopathy, a multimodality study

Abstract Background Microvascular dysfunction (MVD) constitutes one of the most important pathophysiological features in hypertrophic cardiomyopathy (HCM). Chronic and recurrent myocardial ischemia potentially contributes to arrhythmic risk, namely to atrial fibrillation (AF). Purpose To analyze the impact of MVD in the occurrence of AF in HCM patients (P), assessed by coronary flow velocity reserve (CFVR) on echocardiography (echo) and ischemia on cardiovascular magnetic resonance (CMR). Methods Prospective study, which enrolled HCM P without obstructive epicardial coronary artery disease, who underwent stress echo and stress CMR. By echo, the evaluation of CFVR in the left anterior descending (LAD) artery was performed in apical three chambers view. Diastolic coronary flow velocity was measured in basal conditions and in hyperemia, induced by adenosine perfusion (0.14 mg/kg/min intravenously, during 2 minutes). CFVR was calculated as the ratio of hyperemic to basal peak diastolic flow velocities. On CMR, perfusion imaging was acquired during regadenoson-induced hyperemia. To quantify the ischemic burden, the myocardium was divided into 32 subsegments (16 AHA segments subdivided into an endocardial and epicardial layer, excluding segment 17) and the ischemic burden was calculated as the number of involved subsegments, assigning 3% of myocardium to each subsegment. Late gadolinium enhancement (LGE) was quantified used the 6 standard deviation method. Kaplan Meyer curves were performed to evaluate the impact of CFVR, ischemia, left atrial volume and LGE in the occurrence of atrial fibrillation during the follow up. Results 73P were enrolled, 47 (64%) males, mean age 54.3(14.8) years. 19 P (26%) had obstructive HCM, mean maximal wall thickness (MWT) was 20.1(4.6)mm, left ventricular (LV) mass 96.9(30.6)g/m2, LV ejection fraction 71.6(8.4)%, left atrial volume (LAV) 47.0(16.8)ml/m2, CFVR LAD 1.8(0.4), ischemic burden 22.5(17.1)% of LV. During the follow up of 54.6(7.8) months (minimum 42months, maximum 80months), P with more severe microvascular dysfunction (CFVR LAD<2.0 and ischemia ≥18% of LV) had significant higher incidence of atrial fibrillation (figure 1). P with CFVR LAD≥2.0 and LAV≤34ml/m2 had significantly less AF comparing to P with CFVR LAD<2.0 and LAV>34ml/m2. Interestingly, P with only one of this risk factors had similar incidence of AF, pointing toward a similar impact of microvascular dysfunction and LA dilatation. Although LGE is a well-known surrogate marker of disease severity, extension of the ischemia seemed to play a more important role in AF development, as patients with ischemia ≥ 18% of LV and LGE < 15% had more AF than P with ischemia < 18% of LV and LGE ≥ 15%. Conclusion Microvascular dysfunction and consequent ischemic burden were linked to AF, which likely reflects advanced disease, involving atrial myocardium beyond LV myocardium, contributing for atrial dysfunction and arrhythmogenicity. Figure 1