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.

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.

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.

Arterial hypertension in patients with takotsubo syndrome: prevalence, long-term outcome, and secondary preventive strategies: a report from the Takotsubo Italian Network register.

AIMS: The aim of this study was to investigate the long-term outcome of takotsubo syndrome (TTS) patients with and without hypertension (HT) and to evaluate the effectiveness of treatment with beta-blockers (BBs) and/or renin-angiotensin-aldosterone system inhibitors (RAASi). METHODS AND RESULTS: The study population includes a register-based, multicentre cohort of consecutive patients with TTS, divided into two groups according to the history of HT. Further stratification was performed for BB/RAASi prescription at discharge. The primary outcome was the composite of all-cause death and TTS recurrence at the longest available follow-up. The propensity score weighting technique was used to account for potential confounding. In the overall population (903 patients, mean age 70 ± 11 years), HT was reported in 66% of cases. At a median 2-year follow-up, there was no difference in the risk of the primary composite outcome between patients with and without HT. The adjusted Cox regression analysis showed a significantly lower risk for the primary outcome [adjusted hazard ratio (aHR): 0.69; 95% confidence interval (CI): 0.49-0.99] in patients who received BB vs. those who did not. Renin-angiotensin-aldosterone system inhibitors treatment was not associated with the primary study outcome. The lower risk for the primary outcome with BB treatment was confirmed in patients with HT (aHR: 0.37; 95% CI: 0.24-0.56) but not in patients without (aHR: 1.83; 95% CI: 0.92-3.64; Pinteraction < 0.001). CONCLUSION: In this TTS study, HT did not affect the long-term risk of adverse events but increased the probability of benefit from BB treatment after discharge. Owing to the favourable outcome impact of BB prescription in TTS patients with HT, a tailored pharmacological therapy should be considered in this cohort.

Although not associated with clinical outcomes, hypertension (HT) seems to modify the long-term effectiveness of pharmacological treatment in patients with takotsubo syndrome (TTS). Beta-blockers improved the overall survival of TTS patients with HT and should be considered as first-line therapy in this patient population. The effectiveness of renin­angiotensin­aldosterone system inhibitors on long-term outcome was not significant regardless of the history of HT.

Association of Coronary Computed Tomography Angiography and Stress Echocardiography with Long-Term Cardiac Outcome: A Comparison Study.

AIMS: This study aimed to assess which variables on coronary computed tomography angiography (CTA) and vasodilator stress-echocardiography (SE) are best associated with long-term cardiac outcome in patients presenting for suspected chronic coronary syndrome (CCS) who performed both tests. METHODS: We identified 397 patients with suspected CCS who, between 2007 and 2019, underwent both SE and CTA within 30 days. Coronary artery calcium score (CACS) and the number of coronary arteries with diameter stenosis >50% were assessed on CTA. The presence of reversible regional wall motion abnormalities (RWMA) and reduced Doppler coronary flow velocity reserve in the left-anterior descending coronary artery (CFVR) were assessed on SE. The association of SE and CTA variables with cardiac outcome (cardiac death or myocardial infarction) was evaluated using Fine and Gray competing risk models. RESULTS: During a median follow-up of 10 years, 38 (9.6%) patients experienced a nonfatal myocardial infarction and 19 (4.8%) died from a cardiac cause. RWMA (HR 7.189, p < 0.001) and a lower CFVR (HR 0.034, p < 0.001) on SE, along with CACS (HR 1.004, p < 0.001) and the number of >50% stenosed coronary vessels (HR 1.975, p < 0.001) on CTA, were each associated with cardiac events. After adjusting for covariates, only CACS and CFVR remained associated (both p < 0.001) with cardiac outcome. CONCLUSION: Our data suggest that only CFVR on vasodilatory SE and CACS on CTA are independently and strongly associated with long-term cardiac outcome, unlike RWMA or the number of stenosed coronary arteries, usually considered the hallmarks of coronary artery disease on each test.

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.

Machine Learning Algorithms for Prediction of Survival by Stress Echocardiography in Chronic Coronary Syndromes.

Stress echocardiography (SE) is based on regional wall motion abnormalities and coronary flow velocity reserve (CFVR). Their independent prognostic capabilities could be better studied with a machine learning (ML) approach. The study aims to assess the SE outcome data by conducting an analysis with an ML approach. We included 6881 prospectively recruited and retrospectively analyzed patients with suspected (n = 4279) or known (n = 2602) coronary artery disease submitted to clinically driven dipyridamole SE. The outcome measure was all-cause death. A random forest survival model was implemented to model the survival function according to the patient's characteristics; 1002 patients recruited by a single, independent center formed the external validation cohort. During a median follow-up of 3.4 years (IQR 1.6−7.5), 814 (12%) patients died. The mortality risk was higher for patients aged >60 years, with a resting ejection fraction < 60%, resting WMSI, positive stress-rest WMSI scores, and CFVR < 3.The C-index performance was 0.79 in the internal and 0.81 in the external validation data set. Survival functions for individual patients were easily obtained with an open access web app. An ML approach can be fruitfully applied to outcome data obtained with SE. Survival showed a constantly increasing relationship with a CFVR < 3.0 and stress-rest wall motion score index > Since processing is largely automated, this approach can be easily scaled to larger and more comprehensive data sets to further refine stratification, guide therapy and be ultimately adopted as an open-source online decision tool.

Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome.

OBJECTIVE: The advantage of beta-blockers has been postulated in patients with Takotsubo syndrome (TTS) given the pathophysiological role of catecholamines. We hypothesised that beta-blocker treatment after discharge may improve the long-term clinical outcome in this patient population. METHODS: This was an observational, multicentre study including consecutive patients with TTS diagnosis prospectively enrolled in the Takotsubo Italian Network (TIN) register from January 2007 to December 2018. TTS was diagnosed according to the TIN, Heart Failure Association and InterTAK Diagnostic Criteria. The primary study outcome was the occurrence of all-cause death at the longest available follow-up; secondary outcomes were TTS recurrence, cardiac and non-cardiac death. RESULTS: The study population included 825 patients (median age: 72.0 (63.0-78.0) years; 91.9 % female): 488 (59.2%) were discharged on beta-blockers and 337 (40.8%) without beta-blockers. The median follow-up was 24.0 months. The adjusted Cox regression analysis showed a significantly lower risk for all-cause death (adjusted HR: 0.563; 95% CI: 0.356 to 0.889) and non-cardiac death (adjusted HR: 0.525; 95% CI: 0.309 to 0.893) in patients receiving versus those not receiving beta-blockers, but no significant differences in terms of TTS recurrence (adjusted HR: 0.607; 95% CI: 0.311 to 1.187) and cardiac death (adjusted HR: 0.699; 95% CI: 0.284 to 1.722). The positive survival effect of beta-blockers was higher in patients with hypertension than in those without (pinteraction=0.014), and in patients who developed cardiogenic shock during the acute phase than in those who did not (pinteraction=0.047). CONCLUSIONS: In this real-world register population, beta-blockers were associated with a significantly higher long-term survival, particularly in patients with hypertension and in those who developed cardiogenic shock during the acute phase.

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.

Safety of surgical masks during physical activity evaluated with graded cycle ergometry test.

BACKGROUND: At the time of the coronavirus disease 2019 (COVID-19) pandemic wearing surgical mask (SM) is recommended for the prevention of contracting or exposing others to airborne transmission of COVID-19. It is somewhat controversial whether wearing SM during exercise affects performance and health status and/or may influence the results. In order to give an answer we planned a prospective, randomized, crossover study to evaluate the effects of wearing a SM or no-SM in 33 (17 male) physically active healthy subjects during a graded exercise cycle ergometry test. METHODS: The two tests were performed in random order in the same subjects. The participants were all tested the same day, after a recovery time of at least of one hour, in order to avoid interferences on physical performances. Arterial oxygen saturation, heart rate and arterial blood pressure were assessed throughout the exercise tests every step of two minutes, at the end of exercise, performed at the same time with and without mask. RESULTS: Wearing SM had no effect on performance, since the duration of cycle ergometry test with SM and without SM median, respectively, was 14.2 (lower-upper quartile 13.9-14.8) versus 14.3 (13.9-15.5) minutes (P=0.094), and median peak power was 150 W (150-180) versus 150 W (120-180) (P=0.754). CONCLUSIONS: When expressed relative to peak exercise performance, no differences were found between wearing or not wearing SM regarding arterial oxygen saturation, or heart rate at any time during the exercise tests. Wearing SM during vigorous exercise had no detrimental effect on cardiovascular parameters, as well as on exercise metrics in all participants. No ventricular repolarization abnormalities and no arrhythmias were reported on the electrocardiograms.

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.

Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging.

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

Human coronary inflammation by computed tomography: Relationship with coronary microvascular dysfunction.

Background A new imaging metric using coronary computed tomography angiography (CCTA), addressing the peri-coronary adipose tissue (PCAT) computed tomography (CT) attenuation, has been clinically validated. This method provides information regarding coronary inflammation. It is unclear how coronary inflammation affects microvascular function. The non-invasive evaluation of coronary flow velocity reserve is widely used in clinical practice using Doppler measurement on the left anterior descending coronary artery (CFVR-lad) during stress-echocardiography (SE). We hypothesize that coronary inflammation affects CFVR-lad and, in the absence of overt CAD, they are significantly correlated. Methods We evaluated the relationship between coronary inflammation (by PCAT CT attenuation) and coronary microvascular function (by CFVR-lad) in subjects with no or non-obstructive (diameter stenosis <70%) coronary artery disease (CAD). Results Two-hundred and two subjects were enrolled in the study. The relationship between PCAT CT attenuation and CFVR-lad show a significant inverse relationship in the entire group of subjects enrolled in the study (r = -0.32, p < 0.001). Correlation between PCAT CT attenuation and CFVR-lad was significant in subjects with no or mild CAD-lad, while this was not the case in subjects with intermediate CAD-lad. The R and R2 were respectively -0.40, -0.16 in subjects without CAD (p < 0.001) and - 0.35 and - 0.12 in subjects with mild CAD-lad (p = 0.001). Conclusions The main finding of the current study is the independent relationship between coronary microvascular function, by Doppler CFVR-lad during SE, in subjects without severely obstructive CAD in the left anterior descending coronary artery, and the level of local coronary inflammation, by PCAT attenuation measurement on CCTA.

Pulmonary Embolism in COVID-19 Pneumonia: An Overlapping Diagnosis or a Misdiagnosis?

Coronavirus pneumonia (COVID-19) is a novel infectious disease with a high mortality rate due to severe acute respiratory syndrome. A 57-year-old woman was admitted to the emergency department (ED) with fever, cough, atypical chest pain, and dyspnea. She remained in the ED for about 48 h while waiting for the result of the COVID-19 oropharyngeal swab. Once she tested positive, she was hospitalized in the pneumological department with a diagnosis of pneumonia based on a chest X-ray and biochemical tests. Although azithromycin and hydroxychloroquine were promptly administered, she had a worsening of dyspnea even with a high-flow oxygen mask. D-dimer was increased, and a computed tomography scan with pulmonary and leg angiogram was positive for bilateral pulmonary embolism, deep-venous thrombosis, and multiple consolidated opacities in the lung parenchyma. This case highlights the fact that, in a pandemic situation, there is a potentially fatal risk of overlooking an alternative diagnosis in a COVID-19 patient who is generally considered as suffering only from pneumonia.

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).