Noninvasive identification of coronary vasospasm by hyperventilation stress echocardiography with a multi-marker protocol
S Dedic, N Boskovic, G A Lanza, N Cambise, V Giga, M Tesic, S Piccirillo, Q Ciampi, L Cortigiani, A Boshchenko, L Balkeviciene, J Celutkiene, P A Pellikka, E Picano, A Djordjevic DikicAbstract
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.CFV at rest and after HYPSENormal and abnormal CFV response