Giga, Vojislav

Abstract Background Angina with non-obstructive coronary artery disease (ANOCA) is increasingly recognized in clinical practice but effective therapy is difficult to apply due to the heterogeneity of pathophysiological substrates: structural coronary microvascular dysfunction (CMD), functional (vasospastic) CMD, epicardial artery vasospasm, non-cardiac chest pain. Current guidelines recommend invasive coronary function testing with inherent limitations in cost, risk, and access. Objective To evaluate the feasibility of a step-wise, multi-marker, multi-stress assessment of ANOCA patients by stress echocardiography (SE). Methods In an observational, prospective, multicenter, international study, we enrolled 1146 ANOCA patients (age =65.6±11.6years, 636 men, 55, %). All patients underwent a vasodilator SE (adenosine or dipyridamole) with coronary flow velocity reserve (CFVR) measurement in the mid-distal left anterior descending artery (LAD). In a subset of patients with a normal CFVR and strong clinical suspicion for vasospasm, a hyperventilation (HYPER) test (30 deep breaths/min for 5 min) was performed, followed by semi-supine exercise (EX) if negative. Positivity criteria were stress-specific: CFVR < 2.0 for vasodilators; coronary flow velocity (CFV) reduction ≤ 10% from baseline with HYPER; inducible RWMA 2.for HYPER and HYPER-EX Results Of the 1146 patients, 244 (21%) showed abnormal CFVR i.e. structural CMD (Figure 1). In the subset of 68 patients with normal vasodilator CFVR , entering a strategy of sequential stepwise approach, 40 pts underwent HYPER showing a paradoxical vasoconstrictor response despite the increase in the double product (59 %), with RWMA in 11 (16%). Of the remaining patients with normal CFVR and normal response to HYPER, 28 underwent HYPER-EX showing inducible RWMA in 7 (10%) patients. The remaining 21 patients (31%) showed all 3 tests normal: see figure 2. Conclusion In patients with ANOCA, a stepwise multi-marker (CFVR and RWMA) and multi-stress (vasodilators, HYPER, and EX) SE identifies 4 distinct phenotypes and actionable therapeutic targets: structural CMD (reduced CFVR with vasodilator); functional vasospastic CMD (paradoxical decrease of CFV with HYPER), epicardial artery vasospasm (inducible RWMA with HYPER or HYPER-EX); non-cardiac chest pain with normal response all tests and all markers. Our research emphasizes the usefulness of versatile, patient-tailored noninvasive testing in patients with ANOCA to unmask the functional heterogeneity of the endotypes underlying the same phenotype. Figures: 1. Overall population of ANOCA (N=1146)-vasodilator CFVR 2. Pilot study in ANOCA with CFVR>2.0 (N=68)Overall population of ANOCA (N=1146) Pilot study in ANOCA with CFVR>2.0

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021–2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Background: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. Methods: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years; ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) <1.85 identified chronotropic incompetence. Results: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve <1.85; 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610; 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579; 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. Conclusions: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.