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Aim The aim of this study was to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicentre, international, effectiveness study. Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. Methods and results From July 2016 to November 2020, we enrolled 3574 all-comers (age 65 ± 11 years, 2070 males, 58%; ejection fraction 60 ± 10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent clinically indicated ABCDE-SE. The employed stress modality was exercise (n = 952, with semi-supine bike, n = 887, or treadmill, n = 65 with adenosine for step D) or pharmacological stress (n = 2622, with vasodilator, n = 2151; or dobutamine, n = 471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only endpoint. Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D, and 37% for E steps. During a median follow-up of 21 months (interquartile range: 13–36), 73 deaths occurred. Global X2 was 49.5 considering clinical variables, 50.7 after step A only (P = NS (not significant)) and 80.6 after B–E steps (P, Graphical Abstract This study recruited 3,574 patients from 13 stress echo laboratories of 5 countries and shows the prognostic value of the new state-of-the art cardiac functional testing with stress echo ABCDE protocol: Step A for regional wall motion abnormalities; step B for B-lines obtained with 4-site simplified scan and lung ultrasound; step C for contractile reserve with volumetric echocardiography; step D for Doppler-based assessment of coronary flow reserve in mid-distal left anterior descending coronary artery; step E for EKG-based heart rate reserve.

Background Recent studies showed that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during inotropic stimulation with dobutamine (DOB), in comparison to vasodilation with adenosine, provides more reliable functional evaluation of myocardial bridging (MB). However, the adequate cut-off value of CFVR during DOB for diagnosing functional significant MB has not been fully established. Purpose The purpose of the study was to evaluate the adequate cut-off value of TTDE- CFVR during DOB for diagnosis of functional significant MB. Methods This prospective study included 79 patients (54 males, mean age 55±10 years) with angiographic evidence of isolated MB on the left anterior descending artery (LAD) and systolic compression ≥50% diameter stenosis. Exercise stress-echocardiography test (ExSE) and TTDE-CFVR in the distal segment of LAD during DOB infusion (DOB: 10–40μg/kg/min) were performed in all patients. Percent diameter stenosis (DS) of MB at end-systole and end-diastole were analyzed using quantitative coronary angiography. Results Exercise-SE was positive for myocardial ischemia in 22/79 (28%). CFVR during peak DOB was significantly lower in SE-positive group in comparison to SE-negative group (1.94±0.16 vs. 2.78±0.53, p Conclusion A cut-off value Funding Acknowledgement Type of funding sources: None.

Background Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B-lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, EKG-based heart rate reserve. Aim: to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicenter, international, effectiveness study. Methods From July 2016 to November 2020, we enrolled 3,574 all-comers (age 65±11 years, 2,070 males, 58%; ejection fraction 60±10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent ABCDE-SE. The employed stress modality was exercise (n=952, with semi-supine bike, n=887, or treadmill, n=65 with adenosine for step D) or pharmacological stress (n=2,622, with vasodilator, n=2,151; or dobutamine, n=471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only end-point. Results Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D and 37% for E step. During a median follow-up of 21 months, 73 deaths occurred. At univariable analysis, predictors of all-cause mortality were step B (hazard ratio, HR: 2.621, 95% Confidence Intervals, CI: 1.654–4.152, p Conclusion ABCDE-SE allows an effective risk stratification of patient global vulnerability. Funding Acknowledgement Type of funding sources: None. Survival curves based on ABCDE score

Background Left atrial volume (LAV) may dilate acutely during exercise stress echocardiography (ESE) in chronic coronary syndromes. Purpose To assess the feasibility and functional correlates of LAV during ESE outside coronary artery disease. Methods We performed ESE (semi-supine bike in 159 or treadmill in 105 patients) in 264 patients (155 male, age 58±15 years) with heart failure with preserved ejection fraction (HFpEF, n=82), heart failure with reduced ejection fraction (HFrEF, n=51) or hypertrophic cardiomyopathy (HCM, n=131). LAV was measured with the biplane disk summation method. LAV-dilators were defined as those with stress-rest increase in LAV index ≥6.8 ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAV. Average E/e', mitral regurgitation (MR, graded from 0 = absent to 3 = severe), left ventricular ejection fraction, systolic pulmonary arterial pressure (SPAP) from tricuspid regurgitant jet velocity and B-lines (4-sites simplified scan) were also measured. Results Measurement success rate was 264/264 (100%) in technically adequate images. At group analysis LAV changes during ESE were heterogeneous, with LAV index increase in HFrEF (rest = 41±26 vs stress = 44±27 ml/m2, p=0.563) and HCM (rest = 39±18 vs stress = 41±17 ml/m2, p=0.444) and mild decrease in HFpEF (rest= 28±12 vs stress = 26±11 ml/m2, p=0.020). At individual patient analysis, LAV dilation occurred in 88 (33%) patients: 9 with HFpEF (11%), 24 with HFrEF (47%), 55 with HCM (42%, p Conclusion LAV assessment during ESE is feasible with high success rate, and LAV dilation is equally frequent with upright treadmill or semi-supine bike exercise. LAV individual response to stress is unpredictable, with a significant dilation occurring more frequently in HCM and HFrEF compared to HFpEF patients. Across all conditions, LAV dilation is correlated to more advanced pulmonary and hemodynamic congestion, higher left ventricular filling pressures and more severe MR during stress. Funding Acknowledgement Type of funding sources: None. LAV dilators vs non-dilators comparison. SPAP value ≥40 mm Hg; E/e' ≥15; MR grade ≥2; B-lines >10 in patients with (blue bars) and without (red bars) LAV dilation.

Background Coronary flow velocity reserve (CFVR) and heart rate reserve (HRR) during vasodilator stress echocardiography (SE) assess coronary microvascular function and cardiac sympathetic reserve respectively. Both CFVR and HRR can be impaired in hypertrophic cardiomyopathy (HCM). Objectives To evaluate the prognostic value of CFVR and HRR during vasodilator SE in HCM. Methods We enrolled 244 HCM patients (age=51±15 years, 116 men) studied with vasodilator SE from 1999 to 2019 in 5 certified centers. Stress modality was either adenosine (Ado, 0.14 mg/kg/min in 2', n=171) or dipyridamole (Dip, 0.84 mg/kg in 6', n=73). Left ventricular outflow tract obstruction was present at rest in 80 patients (33%). We assessed CFVR in left anterior descending coronary artery (by TTE in 225, and TEE in 19 patients) and HRR (peak/rest heart rate). Abnormal values of HRR were based on receiver operating characteristics for Ado and Dip separately calculated. All patients completed the follow-up. Results CFVR was 2.17±0.46 for Dip and 2.13±0.43 for Ado (p=ns); HRR was 1.36±0.19 for Dip and 1.10±0.16 for Ado (p Conclusions A reduced CFVR and blunted HRR during vasodilator SE identify distinct phenotypes and show independent value in predicting outcome in HCM patients. Funding Acknowledgement Type of funding sources: None. Figure 1. Kaplan-Meier spontaneous event-free survival curves based on HRR and CFVR. Kaplan-Meier survival curves (considering spontaneous events) in patients stratified with the abnormal HRR and/or CFVR. Number of patients at risk per year is shown.

Funding Acknowledgements Type of funding sources: None. Introduction Since mitral regurgitation (MR) is a very common finding in patients with hypertrophic cardiomyopathy (HCM), the evaluation of the mitral valve anatomy and the degree of MR is of utmost importance in this population. However, data regarding the prognostic value of different degrees of MR in HCM remains scarce. Purpose The aim of this study was to determine whether the presence of a higher degree of MR affects: 1) long term prognosis; 2) clinical and echocardiographic presentation of HCM patients. Material and Methods We included prospectively 102 patients, diagnosed with primary asymmetric HCM. The degree of MR was determined echocardiographicaly according to current recommendations of the American Association of Echocardiography. According to the MR severity, patients were divided into 2 groups: Group 1 (n = 52) with no/trace or mild MR and Group 2 with moderate or moderate to severe MR. All patients had clinical and echocardiographic examination, 24-hour Holter ECG and NT pro BNP analysis performed. The primary outcome was a composite of: 1) HCM related death or sudden death; 2) hospitalization due to acute heart failure; 3) sustained ventricular tachycardia; 4) ischemic stroke. Results Patients with higher MR degree had more frequent chest pain (p = 0.039), syncope (p = 0.041) and NYHA II functional class (p 10), as well as higher levels of NT pro BNP (p = 0.001). By Kaplan-Meier analysis we demonstrated that the event free survival rate during follow up of median 75 (IQR 48-103) months was significantly higher in Group 1 compared to the Group 2 (79% vs. 46%, p Conclusion Presence of moderate, or moderate to severe MR was associated with poor long-term outcome of HCM patients. These results indicate the importance of an adequate MR assessment and detailed evaluation of the mitral valve anatomy in the prediction of complications and adequate treatment of patients with HCM. Abstract Figure.

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 Results The double product increased during HYP, in comparison to rest (13 337 vs 9858, p 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

Background Heart rate reserve (HRR) during exercise evaluates chronotropic incompetence and is a prognostically important marker of cardiac autonomic dysfunction, additive to regional wall motion abnormalities (RWMA) in patients with coronary artery disease. Objectives To assess determinants and prognostic value of HRR in patients with hypertrophic cardiomyopathy (HCM). Methods From 1998 to 2019, we enrolled 774 HCM patients (age = 48.8±15.9 years, 410 men) with exercise stress echocardiography (ESE) in 10 certified centres of the international stress echo network. During ESE we assessed: left ventricular outflow tract obstruction (LVOTO, significant when >50 mmHg); RWMA; HRR (peak/ rest heart rate), 344 in beta-blockers therapy (44.4%). Patients were followed for a median 49 months (IQ range, 25–78 months). The study end-point was all-cause mortality. Results During ESE, we observed stress-induced RWMA in 42 (5.4%) and LVOTO in 248 (33%); HRR was 1.92.±0.41. There were no difference in patients with normal and abnormal HRR with and without beta-blockers therapy (147, 41.1% vs 211, 58.9%, p=0.079). During follow-up, 43 deaths occurred. Beta blockers therapy in univariate analysis did not have prognostic role (HR 1.105, 95% CI 0.602–2.028, p=0.768). The lowest HRR quartile (≤1.62) had a 10-fold higher 6-year death rate (10.9%) than the highest quartile (>2.16, 1.04%): see figure. At multivariable analysis, lowest HRR quartile (HR 2.074, 95% CI 1.082–6.773, p=0.034), age (HR 1.045, 95% CI 1.014–1.077, p=0.004), maximal wall thickness (HR 1.137, 95% CI 1.054–1.226, p=0.001), stress-induced RWMA s(HR 4.289, 95% CI 1.733–10.615, p=0.002) and ≥ moderate mitral regurgitation at rest (HR 3.127, 95% CI 1.507–6.488, p=0.002) predicted death. Conclusions A blunted HRR during ESE predicts adverse outcome independent of inducible RWMA in HCM patients. Autonomic dysfunction deserves consideration as a potential therapeutic target in this disease. Figure 1 Funding Acknowledgement Type of funding source: None

Background Exercise and dobutamine stress may induce acute left atrial volume index (LAVI) dilatation in 1 out 10 patients. The effect of vasodilator stress in LAVI remains unknown. Purpose To assess the feasibility and functional correlates of LAVI change during dipyridamole stress echocardiography (SE). Methods We studied 149 patients (99 male, age 66±10 years, ejection fraction 59±8%, 64 with previous myocardial infarction), who underwent dipyridamole ABCDE-SE. LAVI was measured with the biplane disk summation method at rest and peak stress: LAVI-dilators were defined as those with stress-rest increase ≥6.8 ml/m2. Criteria for abnormal response of ABCDE-SE were: stress-induced changes in regional wall motion abnormalities (RWMA) for step A; B-lines at peak stress ≥2 for step B (4-site simplified scan, each site scored from 0= A-lines or black lung to 10= white lung for coalescing B-lines); reduced left ventricular contractile reserve (LVCR, peak/ rest based on force) ≤1.1 for step C; abnormal coronary flow velocity reserve (CFVR) ≤2.0, assessed by pulsed wave Doppler sampling in left anterior descending coronary artery for step D; abnormal heart rate reserve (HRR, peak/rest heart rate) ≤1.22 for step E. Results LAVI dilation occurred in 13 patients (9%). The positivity was for step A: RWMA in 6 pts (4%); step B: presence of peak B-lines in 12 pts (8%); step C: abnormal LCVR in 14 pts (9%); step D: reduced CFVR in 17 pts (11%) and step E: abnormal HRR in 46 pts (31%). LAVI dilators showed significantly higher incidence of positivity of steps A-B-C-D (see figure) compared to patients without LAVI dilatation. Conclusion Evaluation of LAVI change during vasodilator SE is feasible, and LAVI dilatation is more frequently found with ischemic (step A), wet (step B), weak (step C) and cold (step D) heart. Figure 1 Funding Acknowledgement Type of funding source: None

Background The new methodological standard in stress echo (SE) is the comprehensive approach with ABCDE protocol: step A for regional wall motion abnormalities (RWMA); step B for B-lines by lung ultrasound; step C for left ventricular contractile reserve (LVCR); step D for Doppler-based coronary flow velocity reserve (CFVR) in left anterior descending coronary artery; and step E for imaging-independent EKG-based heart rate reserve (HRR). Purpose To assess the feasibility of ABCDE-SE in a prospective, large scale, multicenter, international, effectiveness study. Methods From September 2016 to December 2019, we enrolled 4,585 all-comers patients (age 63±11 years, 2,566 males, 56%; ejection fraction 61±9%) with known or suspected chronic coronary artery disease referred to clinically-driven SE with exercise (n=1,774, 38.7%), dipyridamole (n=2,403, 52.4%), dobutamine (n=375, 8.2%) or adenosine (n=33, 0.7%). Recruitment involved 13-certified laboratories of 7 countries. All patients underwent ABCDE-SE. The same transducer was used for cardiac and lung scan. Criteria for abnormal response were: stress-induced changes in RWMA in 2 contiguous segments for step A; stress-rest increase in B-lines ≥2 for step B (4-site simplified scan, each site scored from 0= A-lines or black lung to 10= white lung for coalescing B-lines); LVCR ≤2.0 for exercise and dobutamine (≤1.1 for vasodilators) for step C; CFVR in LAD ≤2.0 for step D; HRR (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators) for step E. Results Success rate was 98%, 100%, 99%, 86% and 100% for A, B, C, D and E steps, respectively. The positivity rate was 19% for A, 27% for B, 35% for C, 27% for D and 37% for E. All 5 parameters were normal in 1,496 patients (32.6%), all 5 were abnormal in 183 patients (4.0%). Most patients had abnormal response of 1 (n=1,356, 29.6%), 2 (n=788, 17.2%), 3 (n=477, 9.7%) or 4 (n=315, 6.9%) criteria (see Figure). Conclusions ABCDE-SE is extremely feasible, user-friendly, with minimal increase in imaging and off-line analysis time. It allows a comprehensive and personalized functional stratification assessing different vulnerabilities: epicardial coronary artery stenosis (step A), pulmonary congestion (step B), global myocardial dysfunction (step C), coronary microcirculatory dysfunction (step D), and cardiac autonomic nervous system imbalance (step E). The SE response is not only black and white with step A but can be effectively titrated from benign green code (all steps negative) to more functionally malignant red code (at least 3 steps positive). Figure 1 Funding Acknowledgement Type of funding source: None

Background A reduction in coronary flow velocity reserve (CFVR) related to coronary microvascular dysfunction is a major mechanism for ischemia in hypertrophic cardiomyopathy (HCM). Hypothesis To assess the functional correlates and prognostic value of CFVR during stress echocardiography (SE) in HCM. Methods We enrolled 201 HCM patients (age 51±14 years, 105 male, 52%; maximal wall thickness: 18±3 mm) studied with CFVR during exercise (n=33, 16.4%), dipyridamole (n=89, 44.3%) or adenosine (n=79, 39.3%) SE in 6 certified centers. CFVR was assessed using pulsed wave Doppler sampling in left anterior descending coronary artery. All patients completed the clinical follow-up. Results During SE mean value of CFVR was 2.11±0.46. No patients showed regional wall motion abnormalities during stress. LV outflow tract obstruction (LVOTO) was present in 34 (16.9%) patients at rest and in 47 (23.4%) at peak stress. CFVR was inversely related to age (r=−0.229, p=0.001) and maximal wall thickness (r=−0.197, p=0.031). During a median follow-up of 26 months (IQ range: 12–48 months), 75 events in 63 patients occurred: 10 deaths, 33 new hospital admission for acute heart failure, 8 sustained ventricular tachycardias and 24 atrial fibrillations. Patients in the lowest tertile (≤1.88) showed the worse prognosis with higher incidence of follow-up events compared to median tertile (1.89–2.29) and highest tertile (≥2.30) (see figure). At multivariable analysis, NYHA functional class (HR: 2.234, 95% CI: 1.398–3.517, p=0.001), presence of LVOTO at rest (HR: 2.958, 95% CI: 1.074–3.570, p=0.028) and lowest tertile of CFVR (HR: 2.144, 95% CI: 1.126–4.081, p=0.011) were the independent predictors of follow-up events. Conclusions In HCM patients, reduction in CFVR is associated to a clearly worse outcome. The spectrum of prognostic stratification is expanded if the response is titrated according to a continuous scale. Figure 1 Funding Acknowledgement Type of funding source: None

Background Two-dimensional (2-D) volumetric exercise stress echocardiography (ESE) provides an integrated view of preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose To assess the dependence of stroke volume (SV) and cardiac output (CO) upon LVCR EDV changes and heart rate (HR) during ESE. Methods We prospectively performed semi-supine bicycle or treadmill ESE in 1,344 patients (age 59.8±11.4 years; 550 female; ejection fraction = 62.5±8%) referred for known or suspected coronary artery disease in 20 quality controlled laboratories of 16 countries from 2016 to 2019. SV was calculated at rest and peak stress from raw measurement of LV EDV and ESV by biplane Simpson rule, 2-D echo. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values Results By selection, all patients had negative SE by wall motion criteria. Of the 1,344 patients included in the study, 448 belonged to the lowest tertile of CO increase. Of them 326 (73%) achieved HR reserve Conclusion Patients with normal CO reserve during exercise usually have a fast, compliant and strong heart. Abnormal CO reserve is associated with heterogeneous hemodynamic responses, with slow, stiff and/or weak hearts. The clarification of underlying hemodynamic heterogeneity is the prerequisite for a personalized treatment, and can be easily extracted from a standard 2-D volumetric SE. Hearts with normal CO are all alike; every heart with abnormal CO is abnormal in its own way. CO % changes in subsets (*p Funding Acknowledgement Type of funding source: None

Background Percutaneous coronary intervention of chronic total coronary occlusion (PCI of CTO) is proved to reduce symptoms of angina and long term survival. Purpose This study aimed to assess systolic and diastolic left ventricular function with standard echocardiographic indices. Methods We analyzed total of 46 CTO patients (age 58 ± 9, 73% male). Measures were obtained with the transducer in the apical four-chamber view. Doppler time intervals were measured from mitral inflow and left ventricular outflow Doppler tracings by pulsed wave Doppler. The isovolumetric relaxation time (IVRT) was measured from closure of the aortic valve to opening of the mitral valve. The isovolumetric contraction time (IVCT) was measured from closure of the mitral valve to opening of the aortic valve. Ejection time (ET) was measured from the opening to the closure of the aortic valve on the LV outflow velocity profile. Myocardial performance index (MPI) is simple method for evaluation of overall cardiac function and is independent of heart rate and blood pressure. MPI was equal to the sum of the IVRT and IVCT divided by the ET. Velocity of early mitral filling wave (E) was measured and divided by average peak early diastolic annular velocity (e") which was measured as average value between septal and lateral side of the mitral annulus using Doppler tissue imaging. The E/e’ ratio was calculated to estimate the LV filling pressures Results Six months after PCI of CTO patients showed no change in ejection fraction (EF) (55.69 ± 8.56% vs. 54.83 ± 8.44%, p = 0.10). MPI was significantly decreased (0.676 ± 0.99 vs. 0.632 ± 0.96 p Conclusion PCI of CTO improves overall cardiac function, particularly diastolic function in patients with reduced ejection fraction.

OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background ABCDE-stress echocardiography (SE) may explore different aspects in the heterogeneous entity of known or suspected heart failure (HF). Aim To assess ABCDE-vasodilator SE in non-ischemic HF Methods In a prospective, observational, multicenter study, we recruited 428 patients with angiographically normal coronary arteries: 148 patients with HF and preserved (>50%) ejection fraction (HFpEF, Group 1); 100 with HF and mid-range (40-50%) ejection fraction (HFmrEF, Group 2); 180 with HF and reduced ( Results All positivity criteria, except A, were more prevalent (p Conclusions ABCDE-vasodilator SE can help to identify the profound pathophysiological heterogeneity underlying a similar clinical presentation in patients with known or suspected HF with angiographically normal coronary arteries. These patients rarely show stress-induced regional wall motion abnormalities (A), but may exhibit pulmonary congestion (B), reduced myocardial functional reserve (C), altered coronary microcirculation (D) and cardiac autonomic dysfunction (E). Abstract 1675 Figure. The positivity rate of ABCDE criteria

Background Percutaneous coronary intervention for chronic total occlusion (PCI CTO) is still high risk procedure and it is doubtful will it become standard of care. There is evidence that it can reduce angina but even silent ischemia represent ischemic burden that ultimately lead to left ventricle remodeling and electrical instability. Purpose Our aim was to access effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) on myocardial function. Methods We compared two groups of pts. First patients with percutaneous coronary intervention of chronic total occlusion with optimal medical therapy and second group - patients with only optimal medical therapy (control group). Echocardiographic exam was performed before randomization and after 6 months of follow-up. Doppler intervals- isovolumetric relaxation time (IVRT), isovolumetric contraction time (IVCT) and ejection time (ET) were measured. MPI (Myocardial performance index) is equal to the sum of the IVRT and IVCT divided by the ET. Velocity of early mitral wave (E) was divided by average peak early diastolic annular velocity (e"). Peak longitudinal strain was assessed in 17 left ventricular segments. Time intervals from start Q/R on electrocardiogram to peak negative strain during the cardiac cycle were assessed. Mechanical dispersion was defined as the standard deviation of this time intervals from 17 segments, reflecting myocardial contraction heterogeneity. Results A total of 94 age matched CTO patients (48 in PCI + OMT group and 46 in OMT) were analyzed. Changes in ejection fraction (EF), diastolic function represented by E/e", global cardiac function represented by MPI, global longitudinal strain (GLS) and myocardial dispersion changes were compared between groups. At follow up between groups in there was no significant change in ejection fraction (EF), diastolic function, GLS and mechanical dispersion, but there was improvement in MPI. Conclusion Myocardial performance index is sensitive marker which can detect subtle improvement in global myocardial function after recanalization of chronic total occlusion.. Variable PCI + OMT (n = 46) OMT (n = 48) ΔOMT vs. ΔPCI + OMT p value baseline At 6month follow up P value baseline At 6month follow up P value EF (%) 55.69 ± 8.56 54.83 ± 8.44 0.10 50.22 ± 11.71 51.42 ± 10.45 0.06 0.71 MPI 0.676 ± 0.99 0.632 ± 0.96

OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background Stress echocardiography (SE) based on regional wall motion abnormalities (RWMA) has established risk stratification capabilities, further enhanced by assessment of coronary flow velocity reserve (CFVR) on mid-distal left anterior descending coronary artery which assesses not only epicardial coronary artery stenosis but also coronary microcirculation. Aim To assess the value of CFVR in predicting outcome Methods From September 2016 to December 2018, we enrolled 1848 patients (age 63 ± 11 years; 1121 males, 60%) with known or suspected coronary artery disease and/or heart failure evaluated with SE (exercise in 631, dipyridamole in 1184, adenosine in 10, dobutamine in 43) in 9 quality-controlled centers of 6 countries. CFVR was measured from pulsed wave Doppler as peak/rest ratio of peak diastolic flow. All patients were followed-up for a median of 16 months. Results CFV was 28 ± 10 cm/s at rest and 62 ± 19 cm/s at peak stress (p 3 months from SE) myocardial revascularizations. At multivariable analysis, stress-induced RWMA (Hazard Ratio 3.883, 95% Confidence Intervals: 2.379-6.336, p Conclusion In patients referred to SE, CFVR assessing coronary microvascular dysfunction allows a more accurate prediction of outcome than RWMA which only detect epicardial coronary artery stenoses. Abstract P1792 Figure. CFVR and event-free survival curves

Background Heart rate recovery (HRR) has been shown to predict cardiovascular and all-cause morbidity and mortality in different populations. Recent studies have indicated the CHA2DS2-VASc score can be used as predictor of mortality in patients with coronary artery disease, without atrial fibrillation. However, the relation between these two parameters has not yet been documented. The Aim: The aim of this study was to determine the relation between CHA2DS2-VASc score and impaired heart rate recovery in patients without inducible myocardial ischemia. Methods Our study comprised of 2699 consecutive patients (1319 male, 42.8%, average age 60 ± 11 years) who underwent treadmill exercise testing (stress echocardiography or stress echocardiography) according to Bruce protocol for the assessment of myocardial ischemia. We excluded patients with the systolic heart failure (left ventricle ejection fraction Results Out of 2699 patients, 378 (12.3%) had a positive test and they were excluded from further analysis. Of the remaining 2321 patients, 251 (10.8%) had an impaired HRR, whereas 2070 (89.2%) had normal HRR. Previously known coronary artery disease (previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft surgery) had 78 (3.4%) patients. Patients with impaired HRR had significantly higher CHA2DS2-VASc score (3.1 ± 1.3 vs 2.3 ± 1.2, p Conclusion CHA2DS2-VASc score is an independent predictor of impaired HRR in patients without inducible ischemia.

OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background Over the last 3 decades, we observed a progressive decline in the prognostic value of a negative stress echo (SE) test based on regional wall motion abnormalities (RWMA), likely reflecting both an increase in risk in patients (older and more often diabetics) as well as a potential decrease in test performance due to concomitant anti-ischemic therapy. Aim To assess the value of SE in predicting outcome in contemporary populations Methods From September 2016 to December 2018, we enrolled 1848 patients (age 63 ± 11 years; 1121 males, 60%) with known or suspected coronary artery disease and/or heart failure evaluated with SE (exercise in 543, dipyridamole in 1184, adenosine in 10, dobutamine in 43) in 9 quality-controlled centers of 6 countries. Wall motion score index (WMSI) was evaluated at rest and peak stress (17-segment model, from 1 = normal-hyperkinetic to 4 = dyskinetic).All patients were followed-up for a median of 16 months. Results WMSI was 1.09 ± 0.23 at rest and increased during stress (1.17 ± 0.32, p3 months from SE) myocardial revascularizations. Multivariable analysis identified stress-induced RWMA (Hazard Ratio 2.754, 95% Confidence Intervals: 2.053-3.963, p2.0) abnormal peak WMSI: see figure. In patients with negative SE, event-rate was 1.4% per year considering hard events (death and myocardial infarction) and 0.8 % per year considering only death. Conclusion RWMA show risk stratification capability in contemporary patients referred to SE testing. The higher the peak WMSI, and the worse the prognosis. Nevertheless, the positivity rate is low (< 20%) and patients with normal baseline and stress function still have a significant event rate. A more comprehensive risk assessment with other parameters is warranted Abstract P1791 Figure. Survival curves and peak WMSI

OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background Coronary microvascular abnormalities determining a reduction of coronary flow velocity reserve (CFVR) have been described in patients (pts) with non-ischemic heart failure (HF). Aim To assess the prognostic value of CFVR in HF. Methods In a prospective, observational, multicenter study, we recruited 333 pts with angiographically normal coronary arteries: 105 patients with HF and preserved (>50%) ejection fraction (HFpEF); 71 with HF and mid-range (40-50%) ejection fraction (HFmrEF); 157 with HF and reduced ( Results After a median follow-up time of 15 months, 78 events occurred: 36 hospital admissions for acute decompensated heart failure, 23 deaths, 16 worsening in NYHA functional class, 2 stroke and 1 late revascularization. Event-free survival was best in patients with preserved CFVR and LVCR and worst in pts with reduced CFVR and impaired LVCR, with intermediate values for patients with either one (CFVR or LVCR) abnormal results: see figure. A preserved CFVR was associated with a better 24-month event-free survival than reduced CFVR in a subset analysis in pts with HFpEF (HR = 16.2, 95% CI, 1.8-145.1, p = 0.001) and in HFrEF (HR = 3.06, 95% CI, 1.6-5.6, p Conclusions A reduction in CFVR identifies a high risk subset in HF patients, outlining a shared role of coronary microvascular abnormalities as a marker and potential therapeutic target of HF, independently of underlying EF. Abstract P1401 Figure. Event-free survival based on CFVR-LVCR

OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background A blunted heart rate reserve (HRR) during exercise or vasodilator stress echo (SE) has been associated with a poor outcome in retrospective studies. Aim. To assess the prognostic value of HRR in patients undergoing SE in prospective study. Methods We prospectively recruited a sample of 1825 patients (none with pacemakers or atrial fibrillation; mean age 63 ± 11 years; 1099 male, 60%; 1125, 62% on beta-blockers at the time of testing). All underwent SE with either exercise (n= 631, 543 with semi-supine bicycle and 88 with post-treadmill) or vasodilator (n = 1194, 1184 with accelerated high dose dipyridamole and 10 with adenosine) SE for evaluation of known or suspected coronary artery disease and/or heart failure in 7 accredited laboratories of 5 countries. HRR was calculated by ECG as the peak/rest HR ratio. All patients were followed-up. Results During a median follow-up time of 480 days, 211 events occurred: 20 deaths, 22 non-fatal myocardial infarctions, 58 hospital admissions for acute decompensated heart failure and 111 late (> 3 months from SE) myocardial revascularizations. Positivity cutoff for HRR identified by ROC analysis was ≤1.67 (sensitivity 51.0, specificity 63.4) in the exercise group and ≤1.32 (sensitivity 65.0, specificity 48.9) in the vasodilator group. The separation was present both in the exercise (left panel) and the vasodilator (right panel) subsets : see figure. At multivariable analysis, blunted HRR was an independent predictor of event-free survival in the overall group (Hazard Ratio 1.422, 95 % Confidence Intervals: 1.055-1.917, p=.021), independent of beta-blocker therapy. Conclusion A blunted HRR is a useful non-imaging predictor of adverse events during both vasodilator and exercise SE, independent of inducible ischemia and beta-blocker therapy. Abstract P1793 Figure. HRR and event-free survival curves

OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background B-lines (also known as comets) by lung ultrasound (LUS) are a marker of pulmonary congestion and interstitial pulmonary edema during stress echocardiography (SE). Aim To assess the prognostic value of B-lines during SE. Methods We prospectively performed transthoracic echocardiography (TTE) and LUS (4-site simplified scan) evaluation at rest and peak stress in 1437 patients (age 63 ± 11 years; 874 males, 61%) referred for exercise (n = 581), vasodilator (n = 819: dipyridamole, n= 809 and adenosine, n= 10) or dobutamine (n = 37) SE for known or suspected coronary artery disease or heart failure. B-lines were assessed by LUS with a 4-site simplified scan (total score from 0-1, dry lung, to 40, alveolar pulmonary edema). Follow-up (median 16 months) was completed in all. Results B-lines were 1.14 [0-35] at rest and increased during stress (2.10 [0-40], p 3 months from SE) myocardial revascularizations. At multivariable analysis, stress-induced regional wall motion abnormalities (Hazard Ratio, HR, 2.842, 95% Confidence Intervals, CI: 2.016-4.005, p10) B-lines at peak stress: see figure. Conclusion B-lines by LUS are a useful adjunct to regional wall motion abnormalities for risk stratification during SE. The presence and number of B-lines during stress allow a titration of risk. The outcome is darker with more comets in the SE sky. Abstract P1403 Figure. Survival curves and peak stress B-lines

OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background Stress echo (SE) risk stratification is based on regional wall motion abnormalities (RWMA). The assessment of global left ventricular contractile reserve (LVCR) based on load-independent Force may refine prognosis. Aim To assess the value of LVCR during SE in predicting outcome Methods From September 2016 to December 2018, we prospectively enrolled 1848 patients (age 63 ± 11 years; 1121 males, 60%) with known or suspected coronary artery disease and/or heart failure evaluated with SE (exercise in 543, dipyridamole in 1184, adenosine in 10, dobutamine in 43) in 9 quality-controlled centers of 6 countries. Force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/end-systolic volume by 2D and biplane Simpson method of disks. When Simpson method was not feasible, apical single plane or linear parasternal methods were used to calculate volumes. Abnormal values of LVCR (peak/ rest) based on force were ≤1.10 for dipyridamole and adenosine; ≤1.61 for exercise or dobutamine. All patients were followed-up for a median of 16 months. Results RWMA and Force-based LVCR were obtained in all pts. Force was 4.24 ± 1.88 mmHg/ml at rest and increased during stress (7.07 ± 4.60 mmHg/ml, p 3 months from SE) myocardial revascularizations. At multivariable analysis, stress-induced RWMA (Hazard Ratio, HR, 2.899, 95% Confidence Intervals, CI: 2.032-4.137, p Conclusion LVCR based on Force is a useful adjunct to RWMA for risk stratification with SE. Abstract P329 Figure. Survival curves and LVCR

Background Coronary collateral circulation (CCC) exerts protective effects on myocardial ischemia due to coronary artery disease (CAD), but the anti-ischemic, pro-CCC effects of exercise (E) with or without heparin (H) co-administration remain unclear. Purpose To establish the anti-ischemic functional efficacy of 2-week cycle of E-to-ischemia twice daily, with or without unfractionated i.v. H immediately before E, in patients with “no-option” CAD Methods In a prospective, single-center, parallel group study design we recruited 32 “no-option” patients (27 males; mean age of 61±8 years) with at least one chronically occluded coronary artery and stable angina, refractory to optimal medical management, not suitable for revascularization therapy and with E-induced ischemia. All underwent a 2-week cycle of E (2 E test per day, 5 days a week, for 2 weeks) and were randomized, with a double-blind design, to i.v. placebo (0.9% saline) versus unfractionated H (100 IU/kg up to a maximum of 5.000 IU iv, 10 min prior to E). Seattle stable angina questionnaire (SAQ), 12-lead E-ECG for time-to-ischemia (treadmill exercise testing), and MDCT angiography for CCC imaging (Rentrop score, from 0= absent to 3= full opacification of occluded vessel) were assessed at entry and re-assessed after treatment for symptomatic, ECG, and anatomic end-points respectively. Results In H+E group (n=16), time to 1 mm ST segment depression (ST-D) increased, and CCC improved, p0.05) (see table). Clinically important change of more 10 points in SAQ was observed regarding physical limitation, angina stability and disease perception in H+E patients, and in only angina frequency in E group. The ECG and angiographic results Heparin + Exercise Placebo + Exercise Rentrop baseline 0.73±0.88 1.06±1.06 Rentrop 2-week 1.6±0.99* 1.19±1.05 Time to ST-D base (s) 269±64 273±176 Time to ST-D 2-week (s) 328±65* 306±151 *p Conclusion A 2-week, 10 E test cycles are well tolerated and effective particularly with H in ameliorating symptoms, E-induced ischemia and CCC in “no-option” CAD patients with refractory angina.

Background Coronary collateral circulation exerts protective effects on myocardial ischemia due to coronary artery disease (CAD) and can be promoted by exercise (E) with heparin (H) co-administration. Whether this arteriogenetic effects is accompanied by functional improvement of left ventricle (LV) during stress remains unknown. Purpose To establish the stress-induced functional effects on LV regional and global function of 2-week cycle of H+E in patients with “no-option” CAD. Methods In a prospective, single-center, double-blind, randomized, parallel-group study we recruited 32 “no-option” patients (27 males; mean age of 61±8 years), with stable angina and CTO, refractory to OMT, not suitable for revascularization and with E-induced ischemia. All underwent 2-week cycle of E (2 E test per day, 5 days a week) and were pre-treated with i.v. 0.9% saline or unfractionated H (100 IU/kg up to maximum of 5.000IU, 10 min prior to E). Canadian Class Score (CCS) and 12-lead E-ECG for time-to-1 mm ST-segment depression were assessed at entry and after treatment. LV function was evaluated during treadmill exercise with conventional and advanced imaging indices: Wall Motion Score Index (WMSI); Ejection Fraction (EF); Force (systolic blood pressure/end-systolic volume); Global Longitudinal Strain (GLS). Results Post-treatment exercise-time and CCS improved in both groups. In H+E patients exercise-time improved from 369.8±107.8 sec to 475.3±114.6 sec (p=0.001) while in E patients improved from 384±152.7 sec to 464.8±134.1 sec (p=0.019). CCS score changed in H+E from 2.6±0.7 to 1.9±0.7 (p=0.000), and in E group from 2.4±0.7 to 2.1±0.9 (p=0.046). At peak exercise, H+E was different from E group for EF and GLS (see Table). Effects of H+E on SE parameters H+E p P+E p *H+E vs P+E STRESS Time 0 vs Time 1 Time 0 vs Time 1 Time 0 Time 1 WMSI 1.377 vs 1.279 0.005 1.404 vs 1.376 0.290 0.626 0.255 EF (%) 60.9 vs 64.8 0.016 61.2 vs 57.8 0.284 0.943 0.016 Force (mmHg/mL) 6.36 vs 6.5 0.158 5.82 vs 4.68 0.209 0.760 0.098 GLS (%) −16.96 vs −18.50 0.001 −15.79 vs −15.60 0.380 0.325 0.027 SE = stress echocardiography; H+E = heparin+exercise; P+E = placebo+exercise; Time 0 = before randomization; Time 1 = after 2-week therapy cycle. *p values. Conclusion A 2-week, H+E cycle is associated with improvement in regional and global LV function during exercise, concordantly shown by conventional (WMSI, EF) and advanced (GLS) echocardiographic indices of LV function. This integrates and supplements the classical objective index based on ST-segment depression, unable to localize and quantify the functional consequences of therapy on myocardial ischemia.

Background The specific role of non-invasive functional testing in a risk stratification of patients with incomplete revascularization after primary percutaneous coronary intervention (pPCI) still needs to be evaluated. The aim of our study was to assess negative prognostic value of stress echocardiography (SECHO) after successful pPCI and incomplete revascularization of non-culprit lesions. Methods Our study consisted of 202 patients (mean age 59±10 years, male 142) successfully treated with pPCI, who performed SECHO according to Bruce protocol in order to assess residual ischemia in coronary artery with non-culprit lesion. Duke treadmill score, functional capacity (Metabolic Equivalents - METs), achieved target heart rate (THR), heart rate recovery (HRR), wall motion score index (WMSI) and ejection fraction were interrogated in all patients. Slow HRR was defined as ≤18 beats/min. Median follow-up of the patients was 70 months (IQR 55–83 months) for the occurrence of cardiovascular death and non-fatal myocardial infarction. We also assessed the independent predictors for the occurrence of the adverse events. Results Out of 202 patients, 42 (20.8%) had positive SECHO test, 4 patients (1.98%) had died due to non-cardiac causes and 7 patients (3.5%) were lost to follow-up. From the remaining 149 patients with negative SECHO, 13 (8.7%) had an adverse event (7 cardiovascular deaths and 6 non-fatal MI). Negative predictive value of SECHO test was 91.3%. Univariate predictors of adverse events were slow HRR (HR 4.343 [95% CI 1.473–14.011], p=0.008), and not achieved THR (HR 0.322 [95% CI 0.105–0.985], p=0.047). By multivariate analysis, only slow HRR remained independent predictor of adverse events (HR 3.324 [95% CI 1.013–10.906], p=0.048). Conclusion SECHO test has excellent negative prognostic value in patients with incomplete revascularization of non-culprit lesions after successful pPCI. Still, particular care should be taken to the patients with slow HRR and negative SECHO due to increased risk for the occurrence of adverse events. Acknowledgement/Funding Ministry of Education and Science of the Republic of Serbia (Grant No III41022)

Background Coronary microvascular disease has been described in heart failure (HF) in presence of angiographically normal epicardial coronary arteries. The prevalence of a reduction of coronary flow velocity reserve (CFVR) in different types of HF and its link with left ventricular contractile reserve (LVCR) is unclear. Aim To assess CFVR and LVCR in HF. Methods In a prospective, observational, multicenter study, we recruited 380 patients (234 male, 61%, age 66±11 years): 143 (38%) with HF and reduced (50%) ejection fraction (HFpEF). A control group of 52 asymptomatic patients (23 male, 44%, age 61±14 years) referred to testing for screening was also selected (Controls). All patients underwent dipyridamole (0.84 mg/kg) stress echocardiography in 12 accredited laboratories of 3 countries (Argentina, Brazil and Italy). CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of left anterior descending (LAD) artery flow. We assessed left ventricular contractile reserve (LVCR) based on global LV Force (systolic blood pressure/end-systolic volume). Results Reduced (≤2.0) CFVR was observed in 0/52 controls (0%); 25/139 HFpEF (18%); 28/98 HFmrEF (29%); 78/143 HFrEF (54%, p LVCR vs CFVR Conclusions CFVR is frequently abnormal in all types of HF, although more frequently and more profoundly in HFrEF. CFVR mirrors contractile reserve in HFrEF and - less tightly - in HFpEF.

Background Hypertrophic cardiomyopathy (HCM) patients with blunted force-frequency relationship assessed with pacing during cardiac catheterization are at greater risk of adverse events. Left ventricular contractile reserve (LVCR) based on force can be obtained noninvasively during exercise stress echocardiography (ESE). Purpose To evaluate the prognostic correlates of force-based LVCR during ESE in HCM. Methods We enrolled 332 HCM patients (age 51±15 years, 193 males, New York Heart Association, NYHA, Class I-III, EF 68±9%, maximal wall thickness 20±5 mm, left ventricular outflow tract gradient, LVOTG, present at rest in 34 pts, 10%) referred for ESE in 7 quality-controlled labs. SE assessment included LVOTG (mm Hg), LV Force (systolic blood pressure by cuff sphygmomanometer + LVOTG/LV end-systolic volume assessed with 2-D, mmHg/ml) and LVCR (peak/rest ratio of LV Force). LV volumes were measured from apical biplane (4- and 2-chamber) views with Simpson method when feasible (n=290) or with linear Teichholz (T) method from parasternal (long- or short-axis) view (n=42). All patients were followed-up. Results Force values were 8.5±6.7 at rest and 15.0±13.7 mmHg/mL at peak stress (P Figure 1. HCM-LVCR Conclusion A non-invasive evaluation of LVOTG, systolic blood pressure and LV end-systolic volume during ESE allows to assess force-based LVCR in HCM. Lower LVCR is associated with greater risk of events at follow-up.

Background Stress echocardiography (SE) relies on regional wall motion and left ventricular contractile reserve (LVCR) based on force (systolic blood pressure/end-systolic volume). An additional non-imaging parameter based on EKG is the blunted heart rate reserve (HRR) which is a simple marker of altered autonomic balance and is associated with worse prognosis independently of ischemia. Aim To assess the relationship between HRR and LVCR in patients undergoing SE. Methods We enrolled 4707 patients (age 63.6±11.3 yrs, 2800 males) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. The employed stress was exercise (n=2062), dipyridamole (n=2007) or dobutamine (n=638). We assessed LVCR (stress/rest ratio of force=systolic blood pressure/end-systolic volume, ESV). Stress-specific abnormal cutoff value of LVCR were Results HRR was related to LVCR at cumulative (n=4707; r=0.351; p Conclusion A blunted HRR is a useful non-imaging predictor of abnormal LVCR response during exercise or pharmacological SE. HRR is a simple biomarker of autonomic unbalance of physiologic and potentially prognostic meaning. A “slow heart” during stress (with blunted HRR) is more often a “weak heart”, with blunted increase in force.

Background B-profile detected by lung ultrasound (LUS) during stress echocardiography (SE) consists in B-lines with lung sliding and mirrors extra-vascular lung water accumulation (“wet lung”), more often found with ischemic regional wall motion abnormalities (RWMA) and/or diastolic dysfunction. B-lines present at rest may also decrease during stress. Aim To assess the frequency and functional correlates of decreasing B-profile (“drying lung” pattern) during SE. Methods We prospectively performed transthoracic echocardiography (TTE) and LUS evaluation at rest and peak stress in 780 patients with B-lines at rest referred for exercise (n=387), vasodilator (n=324) or dobutamine (n=69) SE for known/suspected coronary artery disease (CAD) and/or heart failure (HF). Recruitment occurred in 17 certified labs of 8 countries with the ABCD protocol, including regional wall motion abnormalities with wall motion score index (WMSI), B-lines, left ventricular contractile reserve (LVCR based on force, systolic blood pressure/end-systolic volume) and Doppler-based coronary flow velocity reserve (CFVR, available in 473 patients). By LUS, we adopted the 4-site simplified scan, each site scored from 0=normal A-lines, to 10=coalescing B-lines. By selection, all patients had resting B-lines score ≥2. Invasive or noninvasive coronary angiography was available in 208 patients. Results Two B-lines stress patterns were identified: Group 1, increase or unchanged pattern (B-line stress score ≥ rest, n=698, 89%); Group 2, decrease-disappearance pattern (B-line stress score < rest for ≤2 points, n=82, 11%). Group 1 showed higher prevalence of inducible ischemia (Group 1 = 74/698 vs. Group 2 = 5/82, 11% vs. 6%, p Disappearing BLines Conclusion About one out of 10 patients with resting B-lines exhibit a decrease-disappearance pattern during stress. They show a more benign coronary anatomic, myocardial functional and coronary physiological profile compared to patients with the fixed-worsening pattern. The drying lung pattern is more often accompanied by a strong (higher peak force), non-ischemic and warm heart (with normal CFVR).

Background The assessment of coronary flow velocity reserve (CFVR) on left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on regional wall motion abnormalities (RWMA). Aim To assess the feasibility and functional correlates of CFVR. Methods In a prospective, observational, multicenter study, we initially screened 3,410 patients (2061, 60%, male; age 63±11 years; ejection fraction, EF=61±9%) with known or suspected coronary artery disease (CAD) and/or heart failure (HF). All patients underwent SE (exercise, n=1288; vasodilator, n=1860; dobutamine, n=262) based on RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. We also assessed B-lines (a sign of pulmonary congestion) with lung ultrasound and left ventricular contractile reserve (LVCR) based on Force (systolic blood pressure/end-systolic volume). Results The success rate for CFVR on LAD was 3,002/3,410 (feasibility=88%): 1,025/1,288 for exercise (80%), 1,766/1,860 (95%) for vasodilator (dipyridamole, n=1,841 and adenosine= 18) and 211/262 (81%) for dobutamine (p Figure 1 Conclusions CFVR is feasible with all SE protocols. The reduced CFVR is often accompanied by RWMA, abnormal LVCR and pulmonary congestion during stress.

BackgroundHeart failure with preserved ejection fraction (HFpEF) is commonly associated with hypertension (HTN). However, resting echocardiography (ECHO) can underestimate the severity of disease. Exercise stress echocardiography (ESE) and the cardiopulmonary exercise testing (CPX) appeared to be useful tests in dynamic assessment of HFpEF. The value of combined exercise stress echocardiography cardiopulmonary testing (ESE-CPX) in the identification of masked HFpEF is still undetermined.ObjectiveThe purpose of this study was to analyse the value of the combined ESE-CPX in the identification of masked HFpEF in patients with HTN, dyspnoea and normal resting left ventricular (LV) systolic and diastolic function.MethodologyWe studied 87 patients with HTN, exertional dyspnoea and normal resting LV function. They all underwent ESE-CPX testing (supine bicycle, ramp protocol, 15 W/min). ECHO measurements were performed at rest, and at peak load. Achievement of peak E/e' ratio>15 was a marker for masked HFpEF.Resu...

Aims The aim of the study was to evaluate the prognostic value of Doppler echocardiographic-derived coronary flow reserve (CFR) over regional wall motion in patients with known or suspected coronary artery disease (CAD) undergoing dipyridamole echocardiography test (DET). Methods and results In a prospective, multicentre, observational study, we evaluated 1145 patients (702 males; 64 ± 11 years) who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echo with CFR evaluation of LAD by Doppler. DET was positive for regional wall motion abnormalities in 291 (25%) and negative in 854 (74%) patients. Mean CFR was 2.2 ± 0.5. At individual patient analysis 702 patients had normal (CFR > 2.0) and 443 had abnormal CFR on LAD. During a median follow-up of 27 months, 109 events occurred: 16 deaths, 17 non-fatal myocardial infarctions, 76 re-hospitalizations for unstable angina. The 30 months infarction-free survival showed the best outcome for those patients with negative DET by wall motion criteria and normal CFR and the worst outcome for patients with positive DET by wall motion and abnormal CFR (99 vs. 68%, P < 0.001). At multivariable analysis, CFR on LAD [hazard ratio (HR) 2.4, 95% CI 1.1–5.4, P = 0.030], medical therapy at time of testing (HR 2.8, 95% CI 1.2–6.6, P = 0.022), DET positivity for regional wall motion abnormalities (HR 3.6, 95% CI 1.5–8.7, P = 0.000), and angina on effort (HR 6.3, 95% CI 2.7–14.8, P = 0.000) were independent prognostic predictors of hard cardiac events. Conclusion In patients with known or suspected CAD, DET result by wall motion criteria and CFR are additive and complementary for the identification of patients at risk of experiencing hard events.

Aims The aim of this study was to assess the prognostic value of myocardial viability recognized as a contractile response to vasodilator stimulation in patients with left ventricular dysfunction in a large scale, prospective, multicentre, observational study. Methods and Results Three hundred and seven patients (mean age 60±10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction and severe left ventricular dysfunction (ejection fraction

Aim The aim of this study was to evaluate simultaneously echocardiographic, haemodynamic and angiographic changes that occur during adenosine and dipyridamole infusion, in patients with one-vessel coronary artery stenosis. This would assess whether deterioration in left ventricular haemodynamics during vasodilator agent infusion is influenced by vasodilation per se, or the development of myocardial ischaemia. Methods and results We performed adenosine (140 μg.kg−1.min−1 over 4 min) and dipyridamole (up to 0·84 mg.kg−1 over 10 min) stress echocardiography tests, together with angiographic and haemodynamic assessment, in 26 patients undergoing elective coronary angioplasty. In 12 of 26 patients, adenosine and dipyridamole tests were repeated 24 h after angioplasty. The criterion for echocardiography test positivity was the appearance of a new transient regional wall motion abnormality. Coronary angiograms were analysed with quantitative coronary arteriography. Adenosine and dipyridamole induced regional dysfunction in 18/26 (69%) and 14/26 (54%) patients before angioplasty, respectively ( P =ns). In the echocardiography-positive patients, the percent diameter stenosis was significantly (P

Background: Correct assessment of the significance of left main coronary artery (LMCA) stenosis on the basis of clinical and angiographic information alone often cannot be done reliably and requires assessment of functional significance of lesions observed on coronary angiography. Aim: The aim of this study was to determine the prognostic value of noninvasively measured coronary flow reserve (CFR) in patients with angiographically assessed intermediate or equivocal LMCA stenosis during long-term follow up. Methods: Hundred patients (59±9 years, 80 male) in whom LMCA was assessed by coronary angiography to be ≤50% diameter stenosis; without significant left anterior descending artery stenosis (LAD), were included in this prospective follow-up study. All patients underwent transthoracic Doppler echocardiography measurements of CFR in medial part of LAD after intravenous adenosine administration to assess functional significance of LMCA stenosis. CFR values were calculated as the ratio between hyperemic maximal flow velocity and resting flow velocity. Patients were followed for the mean period of 27±10 months for the occurrence of composite end point including cardiovascular death, myocardial infarction, hospitalization due to unstable angina and clinically guided revascularization. Results: 91 patient completed follow-up. Events occurred in 16. Mean CFR value of 1.80±0.44 for patients having events was significantly lower, compared to those who were free of events where mean CFR value was 2.4±0.44 (p

s S183 Eur J Echocardiography Abstracts Supplement, December 2006 11 pts (8 men, mean age 60±11 years) received on top of their unchanged medication the ARB Irbesartan (300 mg two times daily, after a titration phase of 14 days) over a total of 3 months. The control group consisted of 9 pts (7 men, mean age 57±12 years) on antihypertensive treatment except ARBs or ACE-inhibitors. Exclusion criteria were relevant left ventricular hypertrophy (septum thickness >13 mm), ARBor ACE-inhibitor treatment in the last 3 month, ejection fraction