Noninvasive identification of coronary vasospasm by hyperventilation stress echocardiography with a multi-marker protocol

Background Vasospastic angina with non-obstructive coronary artery stenosis (ANOCA) is an underdiagnosed cause of ischemia, usually identified with invasive testing. Objective To evaluate hyperventilation stress echocardiography (HYPSE) for identifying coronary vasospastic endotypes. Methods In a prospective, multi-center study we enrolled 131 patients with ANOCA (mean age 57 ± 12 years; 73% women. All enrolled patients, with the exception of six, demonstrated normal coronary flow velocity reserve during the vasodilator test. HYPSE was performed off anti-ischemic therapy in 6 accredited laboratories. Clinical suspicion of coronary vasospasm was present with at least one of the following criteria: angina at rest (n=84) and/or on exercise with variable threshold (n=89), marked circadian variation with early morning peak (n=24), angina precipitated by cold exposure (n=30) or emotion/stress (n=22), or myocardial infarction with non-obstructive coronary stenosis (n=18). The HYPSE protocol consisted of 5 minutes of hyperventilation at a respiratory rate of 30 breaths per minute. Previously validated criteria of abnormal vasospastic response were inducible RWMA (a marker of epicardial spasm) or a ≥ 10% reduction in CFV from baseline (a marker of microvascular spasm) in the mid-distal left anterior descending coronary artery. Follow-up at 12 months was available in all. Results HYPSE was completed in all patients, without significant side effects. The double product increased after hyperventilation (9570 ± 2303 to. 13017 ± 3202 mmHg*bpm; p < 0.001). HYPSE response was abnormal for either one (inducible RWMA or CFV reduction) or both in 48 patients (36.6%). Inducible RWMA occurred in 8/131 (6.1%), CFV reduction was observed in 44/131 (33.6%). Figure 1 and 2. All diagnosed patients received targeted therapy (calcium-antagonists/nitrates). At follow-up, 2 had unstable angina, and event rates were similarly low in patients with normal (0/83, 0%) and abnormal HYPSE (2/48, 4.16%, p=ns). Conclusion In ANOCA patients with clinical suspicion of coronary vasospasm and with normal coronary flow velocity reserve on conventional stress echo testing, a multi-marker HYPSE approach, using RWMA and CFV as complementary markers of vasospasm is feasible and safely identifies vasospastic endotypes, guiding personalized therapy.