Hyperventilation echocardiography in INOCA: the HEROIC study

Abstract

Abstract Background Patients with ischemia and no obstructive coronary artery disease (INOCA) are a heterogeneous group and an unmet diagnostic challenge. Noninvasive Doppler is a feasible tool to assess coronary flow velocity (CFV) in left anterior descending coronary artery (LAD) during stress echocardiography (SE). Aim To assess CFV response during coronary vasoconstrictor and vasodilator stimuli in INOCA patients. Methods In a prospective single center study, we enrolled 16 INOCA patients (age 60±12 years, 15 females) with previously normal angiograms. All underwent SE testing with hyperventilation (HYP, respiratory rate of 30 per min for 5') followed by supine bicycle exercise (HYP+EXE); and adenosine CFV evaluation (ADO, 0.84 mg/kg in 1 min) on the other day. The ratio of peak/rest changes of CFV during HYP in LAD was taken as an index of vasoconstriction, and CFV reserve was evaluated after EXE. An abnormal response to HYP was a CFV ratio <1.0 (vasoconstrictor response). An abnormal response to ADO was a CFV reserve <2.0 (blunted vasodilatory response). CFVR at peak HYP+ EXE was an indicator of endothelial dependent vasodilatation. Results The double product increased during HYP, in comparison to rest (13 337 vs 9858, p<0.001), and further increase with EXE (21 118 vs HYP, p<0.001). Chest pain or dyspnea were present in 2/16 pts during HYP, and in 5/16 patients during HYP+EXE (12.5% vs 31.25%, p=0.083). ST segment depression (≥1mm) was present in 1/16 patients during HYP, and 3/16 during HYP+EXE. Two patients showed regional wall motion abnormalities with HYP+EXE. CFVR response was blunted in 9/16 patients during HYP+EXE, and abnormal for vasoconstriction during HYP in 6. Vasodilation during ADO was preserved in all patients. There was significant difference between CFVR response during HYP+EXE and ADO (1.9±0.5 vs 2.4±0.4 respectively, p=0.039), and between CFVR HYP and ADO (1.2±0.3 vs 2.4±0.4, p<0.001). Conclusion In INOCA patients, HYP+EXE is a more powerful ischemic stress than HYP alone and unmasks abnormalities in regional wall motion and/or CFV response in over one- half of patients, likely unmasking the underlying abnormal coronary vasomotor response of large epicardial and/ or small coronary vessels. INOCA patients show profound heterogeneity of coronary vasomotor responses which can be detected with a combined vasodilator - vasoconstrictor SE approach with CFV assessment. The clarification of underlying coronary microcirculatory heterogeneity is the prerequisite for a personalized treatment, and can be easily extracted from CFV-SE. Normal INOCA hearts are all alike, every abnormal heart is abnormal in its own way. Funding Acknowledgement Type of funding source: None