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.

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.

Coronary Flow, Left Ventricular Contractile and Heart Rate Reserve in Non-Ischemic Heart Failure.

Background: Left ventricular contractile reserve (LVCR), coronary flow velocity reserve (CFVR), and heart rate reserve (HRR) affect outcome in heart failure (HF). They can be simultaneously measured during dipyridamole stress echocardiography (DSE). Aim: To assess the value of comprehensive DSE in patients with non-ischemic HF. Methods: We evaluated 610 patients with HF, no history of coronary artery disease, and no inducible regional wall motion abnormalities: 270 patients with preserved ejection fraction (≥50%), 146 patients with mid-range ejection fraction (40-49%), and 194 patients with reduced ejection fraction (<40%). All underwent DSE (0.84 mg/kg in 6') in 7 accredited laboratories. We measured LVCR (abnormal value ≤ 1.1), CFVR in left anterior descending artery (abnormal value: ≤2.0), and HRR (peak/rest heart rate; abnormal value: ≤1.22). All patients were followed up. Results: Abnormal CFVR, LVCR, and HRR occurred in 29%, 45%, and 47% of patients, respectively (p < 0.001). After a median follow-up time of 20 months (interquartile range: 12-32 months), 113 hard events occurred in 105 patients with 41 deaths, 8 myocardial infarctions, 61 admissions for acute HF, and 3 strokes. The annual mortality rates were 0.8% in 200 patients with none abnormal criteria, 1.8% in 184 patients with 1 abnormal criterion, 7.1% in 130 patients with 2 abnormal criteria, 7.5% in 96 patients with 3 abnormal criteria. Conclusions: Abnormal LVCR, CFVR, and HRR were frequent during DSE in non-ischemic HF patients. They target different pathophysiological vulnerabilities (myocardial function, coronary microcirculation, and cardiac autonomic balance) and are useful for outcome prediction.

Coronavirus disease 2019 infection in patients with recent cardiac surgery: does chronic anticoagulant therapy have a protective effect?

AIMS: The aim of this study was to evaluate the clinical course of COVID-19 in patients who had recently undergone a cardiac procedure and were inpatients in a cardiac rehabilitation department. METHODS: All patients hospitalized from 1 February to 15 March 2020 were included in the study (n = 35; 16 men; mean age 78 years). The overall population was divided into two groups: group 1 included 10 patients who presented with a clinical picture of COVID-19 infection and were isolated, and group 2 included 25 patients who were COVID-19-negative. In group 1, nine patients were on chronic oral anticoagulant therapy and one patient was on acetylsalicylic acid (ASA) and clopidogrel. A chest computed tomography scan revealed interstitial pneumonia in all 10 patients. RESULTS: During hospitalization, COVID-19 patients received azithromycin and hydroxychloroquine in addition to their ongoing therapy. Only the patient on ASA with clopidogrel therapy was transferred to the ICU for mechanical ventilation because of worsening respiratory failure, and subsequently died from cardiorespiratory arrest. All other patients on chronic anticoagulant therapy recovered and were discharged. CONCLUSION: Our study suggests that COVID-19 patients on chronic anticoagulant therapy may have a more favorable and less complicated clinical course. Further prospective studies are warranted to confirm this preliminary observation.

Lung Ultrasound and Pulmonary Congestion During Stress Echocardiography.

OBJECTIVES: The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE). BACKGROUND: B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE. METHODS: The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up. RESULTS: According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction. CONCLUSIONS: Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020-The International Stress Echo Study [SE2020]; NCT03049995).

Functional, Anatomical, and Prognostic Correlates of Coronary Flow Velocity Reserve During Stress Echocardiography.

BACKGROUND: The assessment of coronary flow velocity reserve (CFVR) in left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on stress-induced regional wall motion abnormalities (RWMA). OBJECTIVES: The purpose of this study was to assess the feasibility and functional correlates of CFVR. METHODS: This prospective, observational, multicenter study initially screened 3,410 patients (2,061 [60%] male; age 63 ± 11 years; ejection fraction 61 ± 9%) with known or suspected coronary artery disease and/or heart failure. All patients underwent SE (exercise, n = 1,288; vasodilator, n = 1,860; dobutamine, n = 262) based on new or worsening 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. A subset of 1,867 patients was followed up. RESULTS: The success rate for CFVR on LAD was 3,002 of 3,410 (feasibility = 88%). Reduced (≤2.0) CFVR was found in 896 of 3,002 (30%) patients. At multivariable logistic regression analysis, inducible RWMA (odds ratio [OR]: 6.5; 95% confidence interval [CI]: 4.9 to 8.5; p < 0.01), abnormal left ventricular contractile reserve (OR: 3.4; 95% CI: 2.7 to 4.2; p < 0.01), and B-lines (OR: 1.5; 95% CI: 1.1 to 1.9; p = 0.01) were associated with reduced CFVR. During a median follow-up time of 16 months, 218 events occurred. RWMA (hazard ratio: 3.8; 95% CI: 2.3 to 6.3; p < 0.001) and reduced CFVR (hazard ratio: 1.5; 95% CI: 1.1 to 2.2; p = 0.009) were independently associated with adverse outcome. CONCLUSIONS: CFVR is feasible with all SE protocols. Reduced CFVR is often accompanied by RWMA, abnormal LVCR, and pulmonary congestion during stress, and shows independent value over RWMA in predicting an adverse outcome.

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.

Quality control of regional wall motion analysis in stress Echo 2020.

BACKGROUND: The trial "Stress Echo (SE) 2020" evaluates novel applications of SE beyond coronary artery disease. The aim of the study was control quality and harmonize reading criteria. METHODS: One reader from 78 centers of the SE 2020 network asked for credentials to read a set of 20 SE video-clips selected by the core lab. All aspiring centers met the pre-requisite of high-volume and the years of experience in SE ranged from 5 to 31years (mean value 18years). The diagnostic gold standard was a reading by the core lab. The a priori determined pass threshold was 18/20 (≥90%). RESULTS: Of the initial 78 who started, 57 completed the first attempt: individual readers' score on first attempt ranged from 07/20 to 20/20 (accuracy from 35% to 100%, mean 78.7±13%) and 44 readers passed it. There was a very poor correlation between years of experience and the reader's score on first attempt (r=-0.161, p=0.231). Of the 13 readers who failed the first attempt, 12 took it again after the web-based session and their accuracy improved (74% vs. 96%, p<0.001). The kappa inter-observer agreement before and after web-based training was 0.59 on first attempt and rose to 0.91 on the last attempt. CONCLUSIONS: In SE reading, the volume of activity or years of experience is not synonymous with diagnostic quality. Qualitative analysis and operator-dependence can become a limiting weakness in clinical practice, in the absence of strict pathways of learning, credentialing and audit.

Stress echocardiography with smartphone: real-time remote reading for regional wall motion.

The diffusion of smart-phones offers access to the best remote expertise in stress echo (SE). To evaluate the reliability of SE based on smart-phone filming and reading. A set of 20 SE video-clips were read in random sequence with a multiple choice six-answer test by ten readers from five different countries (Italy, Brazil, Serbia, Bulgaria, Russia) of the "SE2020" study network. The gold standard to assess accuracy was a core-lab expert reader in agreement with angiographic verification (0 = wrong, 1 = right). The same set of 20 SE studies were read, in random order and >2 months apart, on desktop Workstation and via smartphones by ten remote readers. Image quality was graded from 1 = poor but readable, to 3 = excellent. Kappa (k) statistics was used to assess intra- and inter-observer agreement. The image quality was comparable in desktop workstation vs. smartphone (2.0 ± 0.5 vs. 2.4 ± 0.7, p = NS). The average reading time per case was similar for desktop versus smartphone (90 ± 39 vs. 82 ± 54 s, p = NS). The overall diagnostic accuracy of the ten readers was similar for desktop workstation vs. smartphone (84 vs. 91%, p = NS). Intra-observer agreement (desktop vs. smartphone) was good (k = 0.81 ± 0.14). Inter-observer agreement was good and similar via desktop or smartphone (k = 0.69 vs. k = 0.72, p = NS). The diagnostic accuracy and consistency of SE reading among certified readers was high and similar via desktop workstation or via smartphone.

Prediction of mortality in patients with right bundle branch block referred for pharmacologic stress echocardiography.

Right bundle branch block (RBBB) is independently associated with all-cause mortality in patients referred for noninvasive evaluation of coronary artery disease. However, further stratification of risk in these patients has not been specifically addressed. The aim of this study was to risk stratify patients with RBBB who were referred for stress echocardiography. The study population was comprised of 343 patients (267 men; age 66 +/- 9 years) with RBBB who underwent pharmacologic stress echocardiography (231 dipyridamole, 112 dobutamine) for evaluation of suspected or known coronary artery disease. Overall mortality was the only end point. Stress echocardiography was positive for ischemia in 109 patients (32%). During follow-up (38 +/- 32 months), 36 deaths occurred. Seventy-three patients underwent revascularization and were censored. Ischemia at stress echocardiography (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.5 to 5.5, p=0.002), left anterior fascicular block (LAFB) (HR 2.8, 95% CI 1.4 to 5.6, p = 0.002), age >65 years (HR 2.1, 95% CI 1.0 to 4.3, p=0.047), and wall motion score index at rest (HR 2.5, 95% CI 1.0 to 6.5, p=0.057) were multivariate predictors of mortality. On the basis of stress echocardiographic result and presence and/or absence of LAFB, 3 levels of risk were identified: (1) low-risk, in cases of no ischemia and no LAFB (49% of the entire study population); (2) intermediate-risk, in cases of ischemia or LAFB only; and (3) high-risk, in cases of ischemia and LAFB. Clinical data, electrocardiography at rest, and stress echocardiographic results can provide effective stratification of risk in patients with RBBB.

Prognostic implications of intraventricular conduction defects in patients undergoing stress echocardiography for suspected coronary artery disease.

PURPOSE: To investigate the prognostic implications of conduction defects in subjects without proven coronary artery disease who had been referred for stress echocardiography. METHODS: The study sample consisted of 1230 patients (574 men and 656 women; mean [+/- SD] age, 63 +/- 10 years) who underwent stress echocardiography with dipyridamole (n = 780) or dobutamine (n = 450) to evaluate suspected coronary artery disease. A summary wall motion score (on a 1 to 4 scale) was calculated. Patients were followed for a mean of 41 +/- 27 months; mortality was the only endpoint. RESULTS: Four hundred and twenty patients (34%) had intraventricular conduction defects on a resting electrocardiogram (173 with complete left bundle branch block, 98 with isolated right bundle branch block, 43 with right bundle branch block with left anterior hemiblock, and 106 with left anterior hemiblock). Ischemia at stress echo (new or worsening of preexisting wall motion abnormality) was found in 250 patients (20%). There were 56 deaths during follow-up; 138 patients underwent revascularization and were censored. Multivariate predictors of mortality were resting wall motion score index (hazard ratio [HR] = 6.0 per unit increase; 95% confidence interval [CI]: 2.3 to 16; P <0.0001), ischemia at stress echo (HR = 3.9; 95% CI: 2.2 to 6.7; P <0.0001), age >65 years (HR = 3.2; 95% CI: 1.7 to 5.9; P <0.0001), hypertension (HR = 1.8; 95% CI: 1.1 to 3.2; P = 0.03), and right bundle branch block with left anterior hemiblock (HR = 3.7; 95% CI: 1.8 to 7.5; P <0.0001). The other three forms of intraventricular conduction defects (left bundle branch block, isolated complete right bundle branch block, and left anterior hemiblock) were not associated with mortality in multivariate analyses, or among the 980 patients who did not have ischemia. CONCLUSION: Right bundle branch block with left anterior hemiblock is an independent predictor of mortality in patients with suspected coronary artery disease undergoing stress echocardiography, whereas isolated right bundle branch block is associated with outcomes similar to those observed in patients with no conduction defects.