Stress Echo 2030: the new ABCDE protocol defining the future of cardiac imaging.

Functional testing with stress echocardiography is based on the detection of regional wall motion abnormality with two-dimensional echocardiography and is embedded in clinical guidelines. Yet, it under-uses the unique versatility of the technique, ideally suited to describe the different functional abnormalities underlying the same wall motion response during stress. Five parameters converge conceptually and methodologically in the state-of-the-art ABCDE protocol, assessing multiple vulnerabilities of the ischemic patient. The five steps of the ABCDE protocol are (1) step A: regional wall motion; (2) step B: B-lines by lung ultrasound assessing extravascular lung water; (3) step C: left ventricular contractile reserve by volumetric two-dimensional echocardiography; (4) step D: coronary flow velocity reserve in mid-distal left anterior descending coronary with pulsed-wave Doppler; and (5) step E: assessment of heart rate reserve with a one-lead electrocardiogram. ABCDE stress echo offers insight into five functional reserves: epicardial flow (A); diastolic (B), contractile (C), coronary microcirculatory (D), and chronotropic reserve (E). The new format is more comprehensive and allows better functional characterization, risk stratification, and personalized tailoring of therapy. ABCDE protocol is an 'ecumenic' and 'omnivorous' functional test, suitable for all stresses and all patients also beyond coronary artery disease. It fits the need for sustainability of the current era in healthcare, since it requires universally available technology, and is low-cost, radiation-free, and nearly carbon-neutral.

Prognostic value of stress echocardiography assessed by the ABCDE protocol.

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 < 0.001 vs. step A). Annual mortality rate ranged from 0.4% person-year for score 0 up to 2.7% person-year for score 5. CONCLUSION: ABCDE-SE allows an effective prediction of survival in patients with chronic coronary syndromes.

Quality control of B-lines analysis in stress Echo 2020.

BACKGROUND: The effectiveness trial "Stress echo (SE) 2020" evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. PURPOSE: To provide web-based upstream quality control and harmonization of B-lines reading criteria. METHODS: 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. RESULTS: All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p < .01), the first attempt success rate was higher (43 vs 28%, p < 0.01), and the drop-out of readers smaller (0 vs 28%, p < .01). CONCLUSIONS: Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly.

Transthoracic Coronary Flow Data at Rest Predict High-Risk Stress Tests.

Background Several recent studies have reported the opportunity to diagnose significant narrowing of the coronary arteries without stress testing using local flow acceleration. Purpose To define how often patients with increased coronary flow velocities at rest (≥ 0.70 m/s) have a positive exercise echocardiography test. Material and Methods A total of 150 patients scheduled for exercise echocardiography were studied using transthoracic Doppler echocardiography in order to assess coronary artery flow velocity before exercise. Pulsed wave Doppler registered blood flow velocity placed on the color signal. The maximal diastolic velocity of coronary flow was measured. Results Of participants, 16% had a velocity of more than 0.70 m/s in the left main/proximal left anterior/proximal left circumflex arteries (LM/pLAD). A significant correlation was observed between the value of the maximal velocity in LM/pLAD and the ejection fraction at the peak of exercise ( r ≈ -0.39, P < 0.0001); between the value of the maximal velocity in LM/pLAD and index of wall motion abnormalities (IWMA) at the peak of exercise ( r ≈ 0.44, P < 0.0001); and between the value of the maximal velocity in LM/pLAD and dIWMA ( r ≈ 0.41, P < 0.0001). Afterwards, severe ischemia in stress echocardiography tests was observed in this group. The average IWMA of these tests was found to be 2.3. Sixty-two angiograms were available for comparison with Doppler data. Conclusion There is a significant correlation between the value of the maximal velocity in LM/pLAD/pLCx at rest and the severity of wall motion abnormalities during exercise tests.

Caffeine and cardiovascular diseases: critical review of current research.

Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains "Which dose is safe?", as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study.

A novel method for left anterior coronary artery flow velocity assessment by transthoracic echocardiography at the peak of a supine bicycle test.

BACKGROUND: Assessment of coronary flow is only performed during pharmacological tests. Supine bicycle tests permit the visualization of coronary flow assessments during exercise. PURPOSE: To assess the parameters of coronary flow in the left anterior descending artery (LAD) during exercise, which could be a sign of significant LAD narrowing. MATERIAL AND METHODS: A total of 253 patients were enrolled: Group 1, 186 non-selective participants before undergoing a coronary angiography; and Group 2, 67 controls without coronary artery disease (CAD). All the patients performed a supine bicycle echocardiography test. Coronary flow velocities and coronary flow velocity reserve (CFVR) were measured at the mid-segment of the LAD during exercise. Patients in Group 1 underwent a coronary angiography. RESULTS: In comparison with participants without significant LAD stenosis, patients with LAD lesions had a lower ΔV (16 ± 21 vs. 27 ± 20 cm/s, P < 0.04) and a lower CFVR (1.5 ± 0.8 vs. 2.0 ± 0.6, P < 0.004). In comparison with patients without significant proximal LAD stenosis, the patients with proximal LAD lesions had a lower flow velocity at the peak of exercise (49 ± 32 vs. 61 ± 19 cm/s, P < 0.02), a lower ΔV (13 ± 19 vs. 26 ± 22 cm/s, P < 0.004), and a lower CFVR (1.4 ± 0.6 vs. 1.9 ± 0.7, P < 0.0001). In comparison with the control group, the patients with LAD stenosis had a lower flow velocity at the peak of exercise, a lower ΔV, and a lower CFVR. CONCLUSION: Non-invasive CFVR measurement in the LAD could provide valuable additional information to a conventional echocardiography exercise test. In routine clinical practice, CFVR is sufficient for a diagnosis of severe stenosis.

Impact of platelet phenotype on myocardial infarction.

In acute myocardial infarction patients the injured vascular wall triggers thrombus formation in the damage site. Fibrin fibers and blood cellular elements are the major components of thrombus formed in acute occlusion of coronary arteries. It has been established that the initial thrombus is primarily composed of activated platelets rapidly stabilized by fibrin fibers. This review highlights the role of platelet membrane phenotype in pathophysiology of myocardial infarction. Here, we regard platelet phenotype as quantitative and qualitative parameters of the plasma membrane outer surface, which are crucial for platelet participation in blood coagulation, development of local inflammation and tissue repair.

High Resting Coronary Flow Velocity by Echocardiography Is Associated With Worse Survival in Patients With Chronic Coronary Syndromes.

BACKGROUND: Resting coronary flow velocity (CFV) in the mid-distal left anterior descending coronary artery can be easily assessed with transthoracic echocardiography. In this observational study, the authors sought to assess the relationship between resting CFV, CFV reserve (CFVR), and outcome in patients with chronic coronary syndromes. METHODS AND RESULTS: In a prospective multicenter study design, the authors retrospectively analyzed 7576 patients (age, 66±11 years; 4312 men) with chronic coronary syndromes and left ventricular ejection fraction ≥50% referred for dipyridamole stress echocardiography. Recruitment (years 2003-2021) involved 7 accredited laboratories, with interobserver variability <10% for CFV measurement at study entry. Baseline peak diastolic CFV was obtained by pulsed-wave Doppler in the mid-distal left anterior descending coronary artery. CFVR (abnormal value ≤2.0) was assessed with dipyridamole. All-cause death was the only end point. The mean CFV of the left anterior descending coronary artery was 31±12 cm/s. The mean CFVR was 2.32±0.60. During a median follow-up of 5.9±4.3 years, 1121 (15%) patients died. At multivariable analysis, resting CFV ≥32 cm/s was identified by a receiver operating curve as the best cutoff and was independently associated with mortality (hazard ratio [HR], 1.24 [95% CI, 1.10-1.40]; P<0.0001) together with CFVR ≤2.0 (HR, 1.78 [95% CI, 1.57-2.02]; P<0.0001), age, diabetes, history of coronary surgery, and left ventricular ejection fraction. When both CFV and CFVR were considered, the mortality rate was highest in patients with resting CFV ≥32 cm/s and CFVR ≤2.0 and lowest in patients with resting CFV <32 cm/s and CFVR >2.0. CONCLUSIONS: High resting CFV is associated with worse survival in patients with chronic coronary syndromes and left ventricular ejection fraction ≥50%. The value is independent and additive to CFVR. The combination of high resting CFV and low CFVR is associated with the worst survival.

Additive prognostic value of high baseline coronary flow velocity to ejection fraction during resting echocardiography: 3-year prospective study.

BACKGROUND: There is a lack of information about the prognostic value of high velocity in coronary arteries during echocardiography. The present study was aimed at investigating the three-year prognostic value of coronary velocity assessment in all patients who were referred for echocardiography examination. METHODS: The prospective study comprises 747 consecutive patients. Death, myocardial infarction (MI), acute coronary syndrome (ACS), and/or revascularisation were defined as major adverse cardiac events (MACE). Routine echocardiography was added with coronary velocity assessment in the left main, anterior descending, or circumflex coronary arteries by the Doppler method. RESULTS: During a median follow-up of 36 months, 192 patients experienced MACE. Deaths occurred more frequently in patients with high local velocity in proximal left-sided segments vs. in middle left-sided segments vs. patients without high coronary velocity (9 vs. 3 vs. 1%, p < 0.0001). Death/MI/ACS occurred in 17 vs. 7 vs. 1%, p < 0.0001, respectively. Age (HR 1.04, 95% CI 1.00; 1.06; p < 0.04), a velocity more than 65 cm/s in any proximal segments of the arteries (HR 4.7, 95% CI 1.9; 11.9; p < 0.002), ejection fraction (HR 0.97, 95% CI 0.94; 0.99; p < 0.007) were strong independent prognostic predictors of death/MI/ACS. The maximal velocity of coronary flow velocity had a significant additive prognostic value to ejection fraction. CONCLUSIONS: The coronary velocity parameters give long-term prognostic information that can be used to identify persons with a high risk of MACE in consecutive non-selected patients.

Prognostic value of Doppler echocardiographic coronary flow velocity assessment at rest in elderly patients.

BACKGROUND: Atherosclerosis and coronary artery disease (CAD) are a common condition and cause of death in the elderly population. There are difficulties with risk assessment in the elderly as the objectification of their symptomatic status can be challenging due to neuromuscular weakness, physical deconditioning or neurological, orthopaedic, peripheral vascular, or respiratory limitations. Non-invasive coronary artery velocity assessment by Doppler method at rest could be helpful in the elderly population. To evaluate the prognostic role of coronary artery ultrasound assessment in a non-selected elderly population in everyday clinical practice. METHODS: One hundred forty-five patients, aged ≥75years (99 women; 80 ± 4 years), formed the study group. Left coronary artery flows were scanned in addition to conventional echocardiography. During a median follow-up of 26 months, 16 deaths and 2 non-fatal MI occurred. RESULTS: In multivariable analysis, maximal coronary velocity was the only independent predictor for mortality (heart rate [HR]: 1.02, 95%, CI: 1.01-1.04, p < .0005) and for mortality/MI (HR: 1.02, 95%, CI: 1.01-1.03, p < .0001). The value of 110 cm/s maximal coronary flow velocity (CFL) in the proximal segments of left arteries was the best predictor for death, sensitivity 50%, specificity 90%, p < .005. The annual mortality rate was 16.6% persons/year for patients with elevated CFL ≥110 cm/s. The value 81 cm/s was the best predictor for death/MI, sensitivity 61%, specificity 80%, p < .0005; annual mortality rate was 11.2% persons/year for patients with elevated CFL ≥81 cm/s (p < .0001). CONCLUSION: Doppler CFL scanning during routine echocardiography is a feasible and valuable tool for assessment of short-term prognosis in elderly patients.

Echocardiographic functional determinants of survival in heart failure with abnormal ejection fraction.

Background and Aims: Patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF) have a heterogeneous prognosis, and assessment of coronary physiology with coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) may complement established predictors based on wall motion and EF. Methods and results: In a prospective multicenter study design, we enrolled 1,408 HF patients (age 66 ± 12 years, 1,035 men), with EF <50%, 743 (53%) with coronary artery disease, and 665 (47%) with normal coronary arteries. Recruitment (years 2004-2022) involved 8 accredited laboratories, with inter-observer variability <10% for CFV measurement. Baseline CFV (abnormal value >31 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. CFVR (abnormal value ≤2.0) was assessed with exercise (n = 99), dobutamine (n = 100), and vasodilator stress (dipyridamole in 1,149, adenosine in 60). Inducible myocardial ischemia was identified with wall motion score index (WMSI) stress > rest (cut-off Δ ≥ 0.12). LV contractile reserve (CR) was identified with WMSI stress < rest (cutoff Δ ≥ 0.25). Test response ranged from score 0 (EF > 30%, CFV ≥ 32 cm/s, CFVR > 2.0, LVCR present, ischemia absent) to score 5 (all steps abnormal). All-cause death was the only endpoint. Results. During a median follow-up of 990 days, 253 patients died. Independent predictors of death were EF (HR: 0.956, 95% CI: 0.943-0.968, p < 0.0001), CFV (HR: 2.407, 95% CI: 1.871-3.096, p < 0.001), CFVR (HR: 3.908, 95% CI: 2.903-5.260, p < 0.001), stress-induced ischemia (HR: 2.223, 95% CI: 1.642-3.009, p < 0.001), and LVCR (HR: 0.524, 95% CI: 0.324-.647, p = 0.008). The annual mortality rate was lowest (1.2%) in patients with a score of 0 (n = 61) and highest (31.9%) in patients with a score of 5 (n = 15, p < 0.001). Conclusion: High resting CFV is associated with worse survival in ischemic and nonischemic HF with reduced EF. The value is independent and additive to resting EF, CFVR, LVCR, and inducible ischemia.

Multiple Phenotypes of Chronic Coronary Syndromes Identified by ABCDE Stress Echocardiography.

BACKGROUND: Regional wall motion abnormality is considered a sensitive and specific marker of ischemia during stress echocardiography (SE). However, ischemia is a multifaceted entity associated with either coronary artery disease (CAD) or angina with normal coronary arteries, a distinction difficult to make using a single sign. The aim of this study was to evaluate the diagnostic potential of the five-step ABCDE SE protocol for CAD detection. METHODS: From the 2016-2022 Stress Echo 2030 study data bank, 3,229 patients were selected (mean age, 66 ± 12 years; 2,089 men [65%]) with known CAD (n = 1,792) or angina with normal coronary arteries (n = 1,437). All patients were studied using both the ABCDE SE protocol and coronary angiography, within 3 months. In step A, regional wall motion abnormality is assessed; in step B, B-lines and diastolic function; in step C, left ventricular contractile reserve; in step D, coronary flow velocity reserve in the left anterior descending coronary artery; and in step E, heart rate reserve. RESULTS: SE response ranged from a score of 0 (all steps normal) to a score of 5 (all steps abnormal). For CAD, rates of abnormal results were 347 for step A (19.4%), 547 (30.5%) for step B, 720 (40.2%) for step C, 615 (34.3%) for step D, and 633 (35.3%) for step E. For angina with normal coronary arteries, rates of abnormal results were 81 (5.6%) for step A, 429 (29.9%) for step B, 432 (30.1%) for step C, 354 (24.6%) for step D, and 445 (31.0%) for step E. The dominant "solitary phenotype" was step B in 109 patients (9.1%). CONCLUSIONS: Stress-induced ischemia presents with a wide range of diagnostic phenotypes, highlighting its complex nature. Using a comprehensive approach such as the advanced ABCDE score, which combines multiple markers, proves to be more valuable than relying on a single marker in isolation.

Rest and Stress Left Atrial Dysfunction in Patients with Atrial Fibrillation.

BACKGROUND: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. AIM: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. METHODS: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. RESULTS: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). CONCLUSIONS: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

Dynamics of coronary artery velocity flow during exercise echocardiography.

PURPOSE: The aim of our study was to acquire non-invasive data from coronary flow velocity profiles during exercise in groups of healthy subjects and of patients with arterial hypertension. MATERIAL AND METHODS: We enrolled 83 patients into two groups: (1) 35 non-selected consecutive healthy subjects; (2) 25 consecutive patients with arterial hypertension. All the patients performed supine bicycle symptoms-limited tests. Throughout exercise the diastolic peaks of coronary flow velocity in LAD were recorded. Coronary flow velocity reserve (CFVR) was calculated off-line. Profiles of coronary artery velocity were acquired for all groups. The coronary artery flow parameters investigated were comparable in healthy and hypertensive patients at every stage. RESULTS: The average diastolic velocities were 54.8 ± 12.9 vs. 51.8 ± 12.2 cm/s, at 50 W; 69.2 ± 17.1 vs 64.4 ± 19.1 cm/s at 75 W; 70.7 ± 16.4 vs. 76.1 ± 19.0 cm/s at 100 W; 80.0 ± 16.0 vs. 72.9 ± 16.1 cm/s at 125 W; 83.7 ± 12.2 vs. 81.4 ± 17.0 at 150 W, p- non-significant, respectively. On average, the healthy group reached CFVR > 2.0 at a heart rate of 110-120 beats/min at 75 W. During supine bicycle exercise, healthy subjects and patients with arterial hypertension have a similar coronary artery flow velocity profile. CONCLUSION: The routine exercise echocardiography test can feasibly be supplemented with the additional measurement of coronary flow velocity during routine supine exercise stress tests, as the normal range of CFVR is reached before submaximal heart rate.

Should we routinely assess coronary artery Doppler in daily echocardiography practice?

A lot of people with coronary artery disease do not have specific symptoms, and myocardial infarction or death are the first manifestation of the disease. New accurate, non-invasive and safe screening methods are required that can assess the prognosis of patients during routine examinations performed on millions of people. The aim of this review was to discuss the current literature regarding the utility of non-invasive ultrasound imaging of the coronary artery in assessing a patient's prognosis in daily practice. Assessment of coronary artery flow during common stress echocardiography or echocardiography can provide additive incremental prognostic information without the burden of radiation. Exercise or pharmacologic stress echocardiography tests combined with coronary flow velocity reserve assessment has advantages over stress tests based only on regional wall motion abnormalities. Scanning of main coronary arteries as an addition to routine echocardiography can reveal patients at high risk of adverse cardiac events in the near future.

Left atrial volume changes during exercise stress echocardiography in heart failure and hypertrophic cardiomyopathy.

OBJECTIVE: We aimed to assess feasibility and functional correlates of left atrial volume index (LAVI) changes during exercise stress echocardiography (ESE). METHODS: ESE on a bike or treadmill was performed in 363 patients with heart failure with preserved ejection fraction (HFpEF, n = 173), reduced ejection fraction (HFrEF, n = 59), or hypertrophic cardiomyopathy (HCM, n = 131). The LAVI stress-rest increase ≥6.8 ml/m2 was defined as dilation. RESULTS: LAVI measurements were feasible in 100%. LAVI did not change in HFrEF being at rest 32 (25-45) vs at stress 36 (24-54) ml/m2, P = NS and in HCM at rest 35 (26-48) vs at stress 38 (28-48) ml/m2, P = NS, whereas it decreased in HFpEF from 30 (24-40) to 29 (21-37) ml/m2 at stress, P = 0.007. LA dilation occurred in 107 (30%) patients (27% with treadmill vs 33% with bike ESE, P = NS): 26 with HFpEF (15%), 26 with HFrEF (44%), and 55 with HCM (42%) with P < 0.001 for HFrEF and HCM vs HFpEF. A multivariate analysis revealed as the predictors for LAVI dilation E/e' > 14 at rest with odds ratio (OR) 4.4, LVEF <50% with OR 2.9, and LAVI at rest <35 ml/m2 with OR 2.7. CONCLUSION: The LAVI assessment during ESE was highly feasible and dilation equally frequent with a treadmill or bike. LA dilation was three-fold more frequent in HCM and HFrEF and could be predicted by increased resting E/e' and impaired EF as well as smaller baseline LAVI.

Pulmonary Congestion During Exercise Stress Echocardiography in Ischemic and Heart Failure Patients.

BACKGROUND: Lung ultrasound detects pulmonary congestion as B-lines at rest, and more frequently, during exercise stress echocardiography (ESE). METHODS: We performed ESE plus lung ultrasound (4-site simplified scan) in 4392 subjects referred for semi-supine bike ESE in 24 certified centers in 9 countries. B-line score ranged from 0 (normal) to 40 (severely abnormal). Five different populations were evaluated: control subjects (n=103); chronic coronary syndromes (n=3701); heart failure with reduced ejection fraction (n=395); heart failure with preserved ejection fraction (n=70); ischemic mitral regurgitation ≥ moderate at rest (n=123). In a subset of 2478 patients, follow-up information was available. RESULTS: During ESE, B-lines increased in all study groups except controls. Age, hypertension, abnormal ejection fraction, peak wall motion score index, and abnormal heart rate reserve were associated with B-lines in multivariable regression analysis. Stress B lines (hazard ratio, 2.179 [95% CI, 1.015-4.680]; P=0.046) and ejection fraction <50% (hazard ratio, 2.942 [95% CI, 1.268-6.822]; P=0.012) were independent predictors of all-cause death (n=29 after a median follow-up of 29 months). CONCLUSIONS: B-lines identify the pulmonary congestion phenotype at rest, and more frequently, during ESE in ischemic and heart failure patients. Stress B-lines may help to refine risk stratification in these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03049995.

Feasibility and value of two-dimensional volumetric stress echocardiography.

BACKGROUND: Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). METHODS: We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638). RESULTS: Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume. CONCLUSIONS: Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Imaging Quality Control, Methodology Harmonization and Clinical Data Management in Stress Echo 2030.

Stress echo (SE) 2030 study is an international, prospective, multicenter cohort study that will include >10,000 patients from ≥20 centers from ≥10 countries. It represents the logical and chronological continuation of the SE 2020 study, which developed, validated, and disseminated the "ABCDE protocol" of SE, more suitable than conventional SE to describe the complex vulnerabilities of the contemporary patient within and beyond coronary artery disease. SE2030 was started with a recruitment plan from 2021 to 2025 (and follow-up to 2030) with 12 subprojects (ranging from coronary artery disease to valvular and post-COVID-19 patients). With these features, the study poses particular challenges on quality control assurance, methodological harmonization, and data management. One of the significant upgrades of SE2030 compared to SE2020 was developing and implementing a Research Electronic Data Capture (REDCap)-based infrastructure for interactive and entirely web-based data management to integrate and optimize reproducible clinical research data. The purposes of our paper were: first, to describe the methodology used for quality control of imaging data, and second, to present the informatic infrastructure developed on RedCap platform for data entry, storage, and management in a large-scale multicenter study.

Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography.

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.