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.

The obesity paradox in the stress echo lab: fat is better for hearts with ischemia or coronary microvascular dysfunction.

BACKGROUND: Obesity is an independent risk factor for coronary artery disease (CAD), but once CAD has developed it has been associated with improved survival ("obesity paradox"). AIM: To assess how obesity affects prognosis in patients with or without inducible ischemic regional wall motion abnormalities (RWMA) and/or abnormal coronary flow velocity reserve (CFVR) during stress echocardiography (SE). METHODS: In an observational retrospective two- center study design, we analyzed 3249 consecutive patients (1907 men; age 66 ± 12 years; body mass index, BMI, 26.9 ± 4.1 kg/m2) with known (n = 1306) or suspected (n = 1943) CAD who underwent dipyridamole SE with simultaneous evaluation of RWMA and CFVR. All-cause death was the outcome end-point. RESULTS: 1075 patients were lean (BMI 18.5-24.9 kg/m2), 1523 overweight (BMI 25.0-29.9 kg/m2), and 651 obese (≥30.0 kg/m2). Ischemic test result for RWMA occurred in 28 (3%) lean, 69 (4%) overweight, and 28 (4%) obese patients (p = 0.03). An abnormal CFVR (≤2.0) was found in 281 (26%) lean, 402 (26%) overweight and 170 (26%) obese patients (p = 0.99). During 68 ± 44 months of follow-up, 496 (15%) patients died. At multivariable Cox analysis, BMI ≥ 30 was an independent predictor of reduced mortality in the 878 patients with stress-induced (≥2 segments) RWMA and/or CFVR abnormality (HR 0.58, 95% CI 0.40-0.84; p = 0.003), while showed no effect at univariate analysis in the 2371 patients with no RWMA and normal CFVR (HR 1.04, 95% CI 0.74-1.46; p = 0.84). CONCLUSIONS: Obesity exerts a "paradoxical" protective effect in patients with stress-induced ischemia and/ or coronary microvascular dysfunction, and shows a neutral effect in patients with normal CFVR and no stress-induced RWMA.

Stress Echocardiography and Strain in Aortic Regurgitation (SESAR protocol): Left ventricular contractile reserve and myocardial work in asymptomatic patients with severe aortic regurgitation.

OBJECTIVES: To analyze left ventricular (LV) myocardial deformation and contractile reserve (CR) in asymptomatic patients with severe aortic regurgitation (AR) at rest and during exercise, and their correlation with functional capacity. BACKGROUND: The natural history of chronic AR is characterized by a prolonged silent phase before onset of symptoms and overt LV dysfunction. Assessment of LV systolic function and contractile reserve has an important role in the decision-making of AR asymptomatic patients. METHODS: Standard echo, lung ultrasound, and LV 2D speckle tracking strain were performed at rest and during exercise in asymptomatic patients with severe AR and in age- and sex-comparable healthy controls. RESULTS: 115 AR patients (male sex 58.2%; 52.3 ± 18.3 years) and 55 controls were enrolled. Baseline LV ejection fraction was comparable between the groups. Resting LV global longitudinal strain (GLS) and myocardial work efficiency (MWE) were significantly reduced in AR (GLS-15.8 ± 2.8 vs -21.4 ± 4.4; P < .001). Patients with AR and CR- showed reduced resting LV GLS and MWE and increased B-lines. MWE was closely related to peak effort watts, VO2 , LV E/e', and B-lines, at a multivariable analysis. Both GLS and MWE were strong independent predictors of CR. A resting LV GLS cutoff of -12% differentiated CR+ and CR- (78% sensitivity and 84% specificity). CONCLUSIONS: The lower resting values of LV GLS and MWE in severe AR asymptomatic patients suggest an early subclinical myocardial damage that seems to be closely associated with lower exercise capacity, greater pulmonary congestion, and blunted LV contractile reserve during stress.

The new clinical standard of integrated quadruple stress echocardiography with ABCD protocol.

BACKGROUND: The detection of regional wall motion abnormalities is the cornerstone of stress echocardiography. Today, stress echo shows increasing trends of utilization due to growing concerns for radiation risk, higher cost and stronger environmental impact of competing techniques. However, it has also limitations: underused ability to identify factors of clinical vulnerability outside coronary artery stenosis; operator-dependence; low positivity rate in contemporary populations; intermediate risk associated with a negative test; limited value of wall motion beyond coronary artery disease. Nevertheless, stress echo has potential to adapt to a changing environment and overcome its current limitations. INTEGRATED-QUADRUPLE STRESS-ECHO: Four parameters now converge conceptually, logistically, and methodologically in the Integrated Quadruple (IQ)-stress echo. They are: 1- regional wall motion abnormalities; 2-B-lines measured by lung ultrasound; 3-left ventricular contractile reserve assessed as the stress/rest ratio of force (systolic arterial pressure by cuff sphygmomanometer/end-systolic volume from 2D); 4- coronary flow velocity reserve on left anterior descending coronary artery (with color-Doppler guided pulsed wave Doppler). IQ-Stress echo allows a synoptic functional assessment of epicardial coronary artery stenosis (wall motion), lung water (B-lines), myocardial function (left ventricular contractile reserve) and coronary small vessels (coronary flow velocity reserve in mid or distal left anterior descending artery). In "ABCD" protocol, A stands for Asynergy (ischemic vs non-ischemic heart); B for B-lines (wet vs dry lung); C for Contractile reserve (weak vs strong heart); D for Doppler flowmetry (warm vs cold heart, since the hyperemic blood flow increases the local temperature of the myocardium). From the technical (acquisition/analysis) viewpoint and required training, B-lines are the kindergarten, left ventricular contractile reserve the primary (for acquisition) and secondary (for analysis) school, wall motion the university, and coronary flow velocity reserve the PhD program of stress echo. CONCLUSION: Stress echo is changing. As an old landline telephone with only one function, yesterday stress echo used one sign (regional wall motion abnormalities) for one patient with coronary artery disease. As a versatile smart-phone with multiple applications, stress echo today uses many signs for different pathophysiological and clinical targets. Large scale effectiveness studies are now in progress in the Stress Echo2020 project with the omnivorous "ABCD" protocol.

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.

Left ventricular contractile reserve by stress echocardiography as a predictor of response to cardiac resynchronization therapy in heart failure: a systematic review and meta-analysis.

BACKGROUND: The presence of left ventricular contractile reserve (LVCR) during stress echo (SE) may provide favorable response to cardiac resynchronization therapy (CRT) in heart failure patients. The aim of the study was to perform a meta-analysis of available SE data in this set of patients. METHODS: From a Pubmed and Advance Google Scholar database web based search scan up to December 2016, we initially identified 5906 records. From this initial set, we removed that did not include SE and duplicate studies. We assessed for eligibility 71 full-text articles assessed for eligibility, and 60 of them did not meet the inclusion criteria as follow: 1) heart failure patients with NYHA class III and IV, depressed ejection fraction (EF <35%) and QRS duration ≥120 ms at study entry; 2) SE with assessment of LVCR; 3) Follow-up data. LVCR during SE was identified as reduction in wall motion score index and/or an increase in EF. RESULTS: Eleven studies with 861 patients (mean age 67 ± 9 years, ejection fraction 25 ± 6%) were included in the meta-analysis. The type of stress was either exercise (n = 2) or dobutamine (n = 9), the latter with low-dose (10 mcg) in two, intermediate-dose (20 mcg) in five, and high-dose (40 mcg) protocol in two studies. LVCR was detected in 555 patients (63%) and CRT-response was present in 584 (66%). The overall odds ratio for LVCR to predict a favorable CRT response was 2.06 (95%, CI 1.70-2-43), Z score: 11.055, p < 0.001. CONCLUSION: The presence of LVCR during SE with either dobutamine or exercise is associated with a greater chance of response to CRT. This parameter is now ready to be tested in a prospective multicenter trial to select patients more likely to benefit from CRT.

Stress echo 2020: the international stress echo study in ischemic and non-ischemic heart disease.

BACKGROUND: Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. METHODS: In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy). RESULTS: We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. CONCLUSIONS: The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls.

Dual imaging stress echocardiography versus computed tomography coronary angiography for risk stratification of patients with chest pain of unknown origin.

BACKGROUND: Dual imaging stress echocardiography, combining the evaluation of wall motion and coronary flow reserve (CFR) on the left anterior descending artery (LAD), and computed tomography coronary angiography (CTCA) are established techniques for assessing prognosis in chest pain patients. In this study we compared the prognostic value of the two methods in a cohort of patients with chest pain having suspected coronary artery disease (CAD). METHODS: A total of 131 patients (76 men; age 68 ± 9 years) with chest pain of unknown origin underwent dipyridamole (up to 0.84 mg/kg over 6 min) stress echo with CFR assessment of LAD by Doppler and CTCA. A CFR ≤ 1.9 was considered abnormal, while > 50% lumen diameter reduction was the criterion for significant CAD at CTCA. RESULTS: Of 131 patients, 34 (26%) had ischemia at stress echo (new wall motion abnormalities), and 56 (43%) had reduced CFR on LAD. Significant coronary stenosis at CTCA was found in 69 (53%) patients. Forty-six patients (84%) with abnormal CFR on LAD showed significant CAD at CTCA (p < 0.001). Calcium score was higher in patients with reduced than in those with normal CFR (265 ± 404 vs 131 ± 336, p = 0.04). During a median follow-up of 7 months (1st to 3rd quartile: 5-13 months), there were 45 major cardiac events (4 deaths, 11 nonfatal myocardial infarctions, and 30 late [≥6 months] coronary revascularizations). At Cox analysis, independent prognostic indicators were calcium score > 100 (HR 2.84, 95% CI 1.33-6.07, p = 0.007), significant CAD at CTCA (HR 2.68, 95% CI 1.23-5.82, p = 0.013), and inducible ischemia or CFR <1.9R on LAD on dual imaging stress echo (HR 2.25, 95% CI 1.05-4.84, p = 0.038). CONCLUSIONS: Functional and anatomical evaluation using, respectively, dual imaging stress echocardiography and CTCA are both effective modalities to risk stratify patients with chest pain of unknown origin, yielding independent and comparable prognostic value. Compared to CTCA, however, stress echocardiography has the advantage of lower cost and of being free of radiations.

Reversible ischaemia and outcome after adjustment for coronary artery disease severity: a multicentre stress-echocardiography registry.

AIMS: To assess the potential association of reversible ischaemia and Doppler coronary flow velocity reserve in the left anterior descending coronary artery (CFVR-LAD) during stress echocardiography (SE) with all-cause mortality and non-fatal myocardial infarction (MI), after correction for anatomic coronary artery disease (CAD) burden and other significant clinical variables. METHODS AND RESULTS: We selected 3191 patients (mean age 66 ± 12 years) from our multicentre SE registry, who underwent both high-dose dipyridamole SE (comprehensive of CFVR-LAD measurement) and coronary angiography within 2 months. All-cause mortality and non-fatal MI were the primary end points. The association of the primary end point with ischaemia severity and CFVR-LAD was assessed, after multivariable adjustment for all other significant clinical and imaging variables, including anatomic CAD severity by the modified Duke Prognostic Index. The primary end point occurred in 767 (24%) patients (death in 409 and non-fatal MI in 375 patients) during a median follow-up of 42 months. Multivariable Cox regression analyses indicated that, among other significant variables, anatomic CAD severity, reversible ischaemia, and CFVR-LAD were all independently associated with the primary end point; reversible ischaemia was also associated with subsequent MI, while CFVR-LAD with mortality, independent of anatomic CAD severity. CONCLUSION: Our study suggests that reversible ischaemia by wall motion assessment and CFVR-LAD on dipyridamole SE are independently associated with dismal outcome in patients with suspected or known stable CAD, even after accounting for angiographic anatomic CAD severity and also independently from which coronary artery is diseased.

Noninvasive evaluation of dynamic microvascular dysfunction in ischemia and no obstructive coronary artery disease patients with suspected vasospasm.

INTRODUCTION: In patients with ischemia and no obstructive coronary artery disease (INOCA), a dynamic coronary microvascular dysfunction (CMD) is frequent but difficult to capture by noninvasive means.The aim of our study was to assess dynamic CMD in INOCA patients with stress echocardiography after vasoconstrictive and vasodilator stimuli. METHODS: In this prospective single-center study, we have enrolled 40 INOCA patients (age 56.3 ±â€Š13 years, 32 women). All participants underwent stress echocardiography with hyperventilation (HYP), followed by supine bicycle exercise (HYP+EXE) and adenosine (ADO). Stress echocardiography included an assessment of regional wall motion abnormality (RWMA) and coronary flow velocity (CFV) in the distal left anterior descending (LAD) coronary artery. RESULTS: HYP induced a 30% increase in rate pressure product (rest = 10 244 ±â€Š2353 vs. HYP = 13 214 ±â€Š3266 mmHg x bpm, P  < 0.001) accompanied by a paradoxical reduction in CFV (HYP< rest) in 21 patients (52%). HYP alone was less effective than HYP+EXE in inducing anginal pain (6/40, 15% vs. 10/40, 25%, P  = 0.046), ST segment changes (6/40, 15% vs. 24/40, 60%, P  < 0.001), and RWMA (6/40, 15% vs. 13/40, 32.5%, P  = 0.008). ADO-induced vasodilation was preserved (≥2.0) in all patients. CONCLUSION: In patients with INOCA, a coronary vasoconstriction after HYP is common, in absence of structural CMD detectable with ADO. HYP+EXE test represents a more powerful ischemia inducer than HYP alone. Stress echocardiography with LAD-CFV may allow the noninvasive assessment of dynamic and structural coronary microcirculation during stress.

The clinical use of stress echocardiography in chronic coronary syndromes and beyond coronary artery disease: a clinical consensus statement from the European Association of Cardiovascular Imaging of the ESC.

Since the 2009 publication of the stress echocardiography expert consensus of the European Association of Echocardiography, and after the 2016 advice of the American Society of Echocardiography-European Association of Cardiovascular Imaging for applications beyond coronary artery disease, new information has become available regarding stress echo. Until recently, the assessment of regional wall motion abnormality was the only universally practiced step of stress echo. In the state-of-the-art ABCDE protocol, regional wall motion abnormality remains the main step A, but at the same time, regional perfusion using ultrasound-contrast agents may be assessed. Diastolic function and pulmonary B-lines are assessed in step B; left ventricular contractile and preload reserve with volumetric echocardiography in step C; Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery in step D; and ECG-based heart rate reserve in non-imaging step E. These five biomarkers converge, conceptually and methodologically, in the ABCDE protocol allowing comprehensive risk stratification of the vulnerable patient with chronic coronary syndromes. The present document summarizes current practice guidelines recommendations and training requirements and harmonizes the clinical guidelines of the European Society of Cardiology in many diverse cardiac conditions, from chronic coronary syndromes to valvular heart disease. The continuous refinement of imaging technology and the diffusion of ultrasound-contrast agents improve image quality, feasibility, and reader accuracy in assessing wall motion and perfusion, left ventricular volumes, and coronary flow velocity. Carotid imaging detects pre-obstructive atherosclerosis and improves risk prediction similarly to coronary atherosclerosis. The revolutionary impact of artificial intelligence on echocardiographic image acquisition and analysis makes stress echo more operator-independent and objective. Stress echo has unique features of low cost, versatility, and universal availability. It does not need ionizing radiation exposure and has near-zero carbon dioxide emissions. Stress echo is a convenient and sustainable choice for functional testing within and beyond coronary artery disease.

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.

Aortopathy and aortic valve surgery in patients with bicuspid aortic valve with and without raphe.

AIM: To evaluate the association between raphe in bicuspid aortic valve (BAV) patients and valve dysfunction, aortopathy and aortic valve surgery in the REBECCA registry [REgistro della valvola aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging (SIECVI)]. METHODS: Prevalence of aortic valve dysfunction and aortopathy was investigated in BAV patients with and without raphe. Aortic valve dysfunction (regurgitation or stenosis) was categorized as mild, moderate and severe. Aortopathy was defined as annulus ≥14 mm/m2; root ≥20 mm/m2; sinotubular junction ≥16 mm/m2; ascending aorta ≥17 mm/m2, and classified in Type A, isolated ascending aorta dilatation; Type B, aortic root and ascending aorta dilatation; and Type C, isolated aortic root dilatation. RESULTS: Overall, 695 patients with BAV were enrolled; 520 (74.8%) with raphe and 175 (25.2%) without raphe. BAV patients with raphe presented more frequently with moderate or severe aortic stenosis than BAV patients without raphe (183 [35.2%] vs 34 [19.4%], p < 0.001). A higher prevalence of aortopathy, particularly Type B, was observed in patients with vs without raphe. At multivariable analysis, raphe was a predictor of aortic valve surgery at three-year follow-up (odds ratio 2.19, 95% confidence interval 1.08-4.44, p < 0.001). CONCLUSIONS: Patients with BAV and raphe have a higher prevalence of significant aortic stenosis, aortopathy, especially Type B, and a higher risk of undergoing aortic valve surgery at three-year follow-up.

Myocardial contractility in the stress echo lab: from pathophysiological toy to clinical tool.

Up-regulation of Ca2+ entry through Ca2+ channels by high rates of beating is involved in the frequency-dependent regulation of contractility: this process is crucial in adaptation to exercise and stress and is universally known as force-frequency relation (FFR). Disturbances in calcium handling play a central role in the disturbed contractile function in myocardial failure. Measurements of twitch tension in isolated left-ventricular strips from explanted cardiomyopathic hearts compared with non-failing hearts show flat or biphasic FFR, while it is up-sloping in normal hearts. Starting in 2003 we introduced the FFR measurement in the stress echo lab using the end-systolic pressure (ESP)/End-systolic volume index (ESVi) ratio (the Suga index) at increasing heart rates. We studied a total of 2,031 patients reported in peer-reviewed journals: 483 during exercise, 34 with pacing, 850 with dobutamine and 664 during dipyridamole stress echo. We demonstrated the feasibility of FFR in the stress echo lab, the clinical usefulness of FFR for diagnosing latent contractile dysfunction in apparently normal hearts, and residual contractile reserve in dilated idiopathic and ischemic cardiomyopathy. In 400 patients with left ventricular dysfunction (ejection fraction 30 ± 9%) with negative stress echocardiography results, event-free survival was higher (p < 0.001) in patients with ΔESPVR (the difference between peak and rest end-systolic pressure-volume ratio, ESPVR) ≥ 0.4 mmHg/mL/m2. The prognostic stratification of patients was better with FFR, beyond the standard LV ejection fraction evaluation, also in the particular settings of severe mitral regurgitation or diabetics without stress-induced ischemia. In the particular setting of selection of heart transplant donors, the stress echo FFR was able to correctly select 34 marginal donor hearts efficiently transplanted in emergency recipients. Starting in 2007, we introduced an operator-independent cutaneous sensor to monitor the FFR: the force is quantified as the sensed pre-ejection myocardial vibration amplitude. We demonstrated that the sensor-derived force changes at increasing heart rates are highly related with both max dP/dt in animal models, and with the stress echo FFR in 220 humans, opening a new window for pervasive cardiac heart failure monitoring in telemedicine systems.

ABCDEG Stress Echocardiography in Aortic Stenosis.

Rest and stress echocardiography (SE) plays a pivotal role in the evaluation of valvular heart disease. The use of SE is recommended in valvular heart disease when there is a mismatch between resting transthoracic echocardiography findings and symptoms. In aortic stenosis (AS), rest echocardiographic analysis is a stepwise approach that begins with the evaluation of aortic valve morphology and proceeds to the measurement of the transvalvular aortic gradient and aortic valve area (AVA) using continuity equations or planimetry. The presence of the following three criteria suggests severe AS: AVA < 1.0 cm2, a peak velocity > 4.0 m/s, or a mean gradient > 40 mmHg. However, in approximately one in three cases, we can observe a discordant AVA < 1 cm2 with a peak velocity < 4.0 m/s or a mean gradient <40 mmHg. This is due to reduced transvalvular flow associated with LV systolic dysfunction (LVEF < 50%) defined as "classical" low-flow low-gradient (LFLG) AS or normal LVEF "paradoxical" LFLG AS. SE has an established role in evaluating LV contractile reserve (CR) patients with reduced LVEF. In classical LFLG AS, LV CR distinguished pseudo-severe AS from truly severe AS. Some observational data suggest that long-term prognosis in asymptomatic severe AS may not be as favorable as previously thought, offering a window of opportunity for intervention prior to the onset of symptoms. Therefore, guidelines recommend evaluating asymptomatic AS with exercise stress in physically active patients, particularly those younger than 70 years, and symptomatic classical LFLG severe AS with low-dose dobutamine SE. A comprehensive SE assessment includes evaluating valve function (gradients), the global systolic function of the LV, and pulmonary congestion. This assessment integrates considerations of blood pressure response, chronotropic reserve, and symptoms. StressEcho 2030 is a prospective, large-scale study that employs a comprehensive protocol (ABCDEG) to analyze the clinical and echocardiographic phenotypes of AS, capturing various vulnerability sources which support stress echo-driven treatment strategies.

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.

Current national availability of advanced echocardiography imaging: real world data from an Italian Society of Echocardiography and Cardiovascular Imaging survey.

Aims: Advanced echocardiographic imaging (AEI) techniques, such as three-dimensional (3D) and multi-chamber speckle-tracking deformation imaging (strain) analysis, have been shown to be more accurate in assessing heart chamber geometry and function when compared with conventional echocardiography providing additional prognostic value. However, incorporating AEI alongside standard examinations may be heterogeneous between echo laboratories (echo labs). Thus, our goal was to gain a better understanding of the many AEI modalities that are available and employed in Italy. Methods and results: The Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) conducted a national survey over a month (November 2022) to describe the use of AEI in Italy. Data were retrieved via an electronic survey based on a structured questionnaire uploaded on the SIECVI website. Data obtained from 173 echo labs were divided into 3 groups, according to the numbers of echocardiograms performed: <250 exams (low-volume activity, 53 centres), between 251 and 550 exams (moderate-volume activity, 62 centres), and ≥550 exams (high-volume activity, 58 centres). Transthoracic echocardiography (TTE) 3D was in use in 75% of centres with a consistent difference between low (55%), medium (71%), and high activity volume (85%) (P = 0.002), while 3D transoesophageal echocardiography (TEE) was in use in 84% of centres, reaching the 95% in high activity volume echo labs (P = 0.006). In centres with available 3D TTE, it was used for the left ventricle (LV) analysis in 67%, for the right ventricle (RV) in 45%, and for the left atrium (LA) in 40%, showing greater use in high-volume centres compared with low- and medium-volume centres (all P < 0.04). Strain analysis was utilized in most echo labs (80%), with a trend towards greater use in high-volume centres than low- and medium-volume centres (77%, 74%, and 90%, respectively; P = 0.08). In centres with available strain analysis, it was mainly employed for the LV (80%) and much less frequently for the RV and LA (49% and 48%, respectively). Conclusion: In Italy, the AEI modalities are more frequently available in centres with high-volume activity but employed only in a few applications, being more frequent in analysing the LV compared with the RV and LA. Therefore, the echocardiography community and SIECVI should promote uniformity and effective training across the Italian centres. Meanwhile, collaborations across centres with various resources and expertise should be encouraged to use the benefits of the AEI.

Exercise Stress Echocardiography in Athletes: Applications, Methodology, and Challenges.

This comprehensive review explores the role of exercise stress echocardiography (ESE) in assessing cardiovascular health in athletes. Athletes often exhibit cardiovascular adaptations because of rigorous physical training, making the differentiation between physiological changes and potential pathological conditions challenging. ESE is a crucial diagnostic tool, offering detailed insights into an athlete's cardiac function, reserve, and possible arrhythmias. This review highlights the methodology of ESE, emphasizing its significance in detecting exercise-induced anomalies and its application in distinguishing between athlete's heart and other cardiovascular diseases. Recent advancements, such as LV global longitudinal strain (GLS) and myocardial work (MW), are introduced as innovative tools for the early detection of latent cardiac dysfunctions. However, the use of ESE also subsumes limitations and possible pitfalls, particularly in interpretation and potential false results, as explained in this article.

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.