We found that the prevalence of ACS-NOCA and MINOCA in the HCM cohort was 14% and 9%, respectively. Our findings underscore that ACS with non-obstructive epicardial coronary arteries in patients with HCM is not uncommon. Previous case reports described patients with MINOCA or ACS-MINOCA [
5‐
10], however, there has been a paucity of case series data on the prevalence of this entity. Maron et al. [
16] examined transmural MI in the absence of atherosclerosis in patients with HCM in cardiac autopsy and necropsy specimens. The prevalence rate of transmural MI with normal coronary artery in their study was 15% although those patients did not have angina at presentation. Yang et al. [
17] reported that 21% of 91 patients with HCM and acute MI had nonstenotic coronary arteries. The prevalence rate of NOCA in our patients with acute MI and ACS was 86% and 51%, respectively. The explanation for a higher rate of NOCA in our cohort may include a higher rate of patients with acute NSTEMI undergoing coronary angiography. Yang et al. did not report the number of patients with acute MI (e.g., NSTEMI) who did not undergo coronary angiography in their study. Previous studies examining epicardial CAD in patients with HCM undergoing coronary angiography reported 47–80% rate of normal coronary arteries [
3,
18]. However, these studies included HCM patients with no clinical context of ACS referred for coronary angiography. Walston et al. found that the classical ECG of acute MI was detected in 8 of the 33 (24%) HCM patients with normal coronary arteries [
3], whereas classical ECG of acute MI in our study was found in 64% of patients with HCM and ACS-NOCA. In the study by Gupta et al. [
19] comparing outcomes of acute MI in patients with HCM and patients with no HCM, NSTEMI was the most common type of MI accounted for 77% of patients with HCM. Similarly, NSTEMI accounted for the majority of ACS in our cohort. Pathophysiological mechanisms of MI in the absence of epicardial disease in patients with HCM were microvascular dysfunction, myocardial bridging, vasospasm, mismatch of myocardial oxygen demand and supply due to the hypertrophied muscle, and structure of intramural small vessels [
20‐
22]. Microvascular dysfunction has been described in patients with HCM with angina [
23,
24]. Foa et al. reported key findings of microvascular remodeling from myectomy specimens, which included luminal narrowing and thickening of the vascular wall [
25]. Previous studies reported that the prevalence of myocardial bridging in patients with HCM diagnosed by coronary angiogram was 15–28% and by CT scan was 50–62% [
2,
26‐
28]. Notably, previous studies included patients with HCM presenting with chronic stable angina and HF undergoing coronary angiogram or CT scan. In contrast, the prevalence of myocardial bridging in our study was low (3%). We hypothesized that myocardial bridging may a play role in chronic stable angina rather than in ACS-NOCA or MINOCA. Another mechanism for the angina described in HCM patients was the LVOT obstruction [
22]. Dawn et al. [
29] demonstrated that LVOT obstruction was a significant predictor for developing chest pain. Nonetheless, our patients with ACS-NOCA had a lower resting LVOT gradient compared with the no ACS-NOCA group. LVOT obstruction is a dynamic phenomenon and usually occurs with exercise. The proportion of LVOT obstruction in our study may be underestimated because we did not perform a routine provocative test in the echocardiography laboratory in all patients. Additionally, we excluded patients with chronic stable angina, HF, or evidence of ischemia by non-invasive testing of the analysis. We found that LV wall thickness was not different between the ACS-NOCA and no ACS-NOCA group. These findings suggest that microvascular disease, intramural coronary artery course, and endothelial dysfunction may play an important role for myocardial ischemia and/or infarction rather than LV mass or LV wall thickness. We found that patients with ACS-NOCA more frequently had a history of VT than those with no ACS-NOCA. Kwon et al. [
30] and Suk et al. [
30,
31] reported that the degree of myocardial scar or fibrosis assessed by cardiac MRI was strongly associated with a history of VT in patients with HCM. Although we did not examine the presence and extent of myocardial scar in this study, we hypothesized that patients with ACS-NOCA may have higher myocardial necrosis frequency or burden than those with no ACS-NOCA.