Updated Estimates of Radiation Risk for Cancer and Cardiovascular Disease: Implications for Cardiology Practice.

This review aims to furnish an updated assessment of the societal healthcare load, including cancer and cardiovascular disease resulting from diagnostic radiologic operations. The previously projected additional cancer risk of 0.9% in a United States 2004 study referred to radiological conditions in 1996 with an X-ray exposure of 0.50 millisievert (mSv) per capita annually. Radiological exposure (radiology + nuclear medicine) has escalated to 2.29 mSv (2016) per capita per year. Low-dose exposures were previously assumed to have a lower biological impact, since they allow the DNA repair system to mitigate molecular damage. However, epidemiological data matured and disproved this assumption, as shown by updated cancer risk assessments derived from the World Health Organization 2013 and the German Institute of Radioprotection 2014 data. The risk of cardiovascular disease aligns within the same order of magnitude as cancer risk and compounds it, as shown by a comprehensive meta-analysis of 93 studies. The collective societal burden arising from the augmented risks of cancer and cardiovascular disease attributable to diagnostic radiology and nuclear medicine is higher than previously thought.

Evaluation and management of patients with coronary chronic total occlusions considered for revascularisation. A clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC, the European Association of Cardiovascular Imaging (EACVI) of the ESC, and the ESC Working Group on Cardiovascular Surgery.

Chronic total occlusions (CTOs) of coronary arteries can be found in the context of chronic or acute coronary syndromes; sometimes they are an incidental finding in those apparently healthy individuals undergoing imaging for preoperative risk assessment. Recently, the invasive management of CTOs has made impressive progress due to sophisticated preinterventional assessment, including advanced non-invasive imaging, the availability of novel and dedicated tools for CTO percutaneous coronary intervention (PCI), and experienced interventionalists working in specialised centres. Thus, it is crucial that referring physicians who see patients with CTO be aware of recent developments and of the initial evaluation requirements for such patients. Besides a careful history and clinical examination, electrocardiograms, exercise tests, and non-invasive imaging modalities are important for selecting the patients most suitable for CTO PCI, while others may be referred to coronary artery bypass graft or optimal medical therapy only. While CTO PCI improves angina and reduces the use of antianginal drugs in patients with symptoms and proven ischaemia, hibernation and/or wall motion abnormalities at baseline or during stress, the effect of CTO PCI on major cardiovascular events is still controversial. This clinical consensus statement specifically focuses on referring physicians, providing a comprehensive algorithm for the preinterventional evaluation of patients with CTO and the current evidence for the clinical effectiveness of the procedure. The proposed care track has been developed by members and with the support of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI), and the European Society of Cardiology (ESC) Working Group on Cardiovascular Surgery.

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.

Right heart failure as a cause of pulmonary congestion in pulmonary arterial hypertension.

AIMS: Recent studies have shown that lung ultrasound-assessed pulmonary congestion is worse in heart failure when pulmonary vascular resistance (PVR) is increased, suggesting a paradoxical relationship between right heart failure and increased lung water content. Accordingly, we wondered if lung ultrasound would reveal otherwise clinically silent pulmonary congestion in patients with pulmonary arterial hypertension (PAH). METHODS AND RESULTS: All patients referred for suspicion of PAH in a tertiary centre from January 2020 to December 2022 underwent a complete diagnostic work-up including echocardiography, lung ultrasound and right heart catheterization. Pulmonary congestion was identified by lung ultrasound B-lines using an 8-site scan. The study enrolled 102 patients with idiopathic PAH (mean age 53 ± 13 years; 71% female). World Health Organization functional classes I, II, and III were found in 2%, 52%, and 46% of them, respectively. N-terminal pro-brain natriuretic peptide (NT-proBNP) was 377 pg/ml (interquartile range [IQR] 218-906). B-lines were identified in 77 out of 102 patients (75%), with a median of 3 [IQR 1-5]. At univariable analysis, B-lines were positively correlated with male sex, age, NT-proBNP, systolic pulmonary artery pressure (sPAP), right atrial pressure (RAP), PVR, left ventricular end-diastolic volume and tricuspid annular plane systolic excursion (TAPSE), and negatively with cardiac output and stroke volume. At multivariable analysis, RAP (p < 0.001), TAPSE/sPAP (p = 0.001), and NT-proBNP (p = 0.04) were independent predictors of B-lines. CONCLUSION: Lung ultrasound commonly discloses pulmonary congestion in PAH. This finding is related to right ventricular to pulmonary artery uncoupling, and may tentatively be explained by increased central venous pressure impeding lymphatic outflow.

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.

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.

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.

[ANMCO Position paper: Ionizing radiation exposure and radioprotection in the cath-lab]. / Position paper ANMCO: Radioesposizione e radioprotezione nei laboratori di cardiologia interventistica.

In the last decades, because of the improvements in the percutaneous treatment of coronary heart disease, valvular heart disease, congenital heart defects, and the increasing number of cardiac resynchronization therapy and cardioverter-defibrillator implantations, the interventional cardiologists' radio-exposure has importantly risen, causing concerns for ionizing radiation-associated diseases such as cancer and neurodegenerative disorders. Consequently, the radiation exposure issue importantly affects operators' safety. However, our knowledge of this field is poor and most operators are unaware to be at risk, especially because of the absence of effective preventive measures. The aim of this ANMCO position paper is to improve the awareness of operators and identify new ways of reducing operator ionizing radiation dose and minimizing the risk.

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.

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.

Coronary flow velocity at rest: a speed limit for a safe prognostic journey?

The study presented by Zagatina and co-workers in the present issue of the Journal raises an interesting issue. Coronary flow velocity at rest is usually associated with dynamic assessment during stress but it may also have an important pathophysiologic and prognostic meaning when evaluated at rest, before stress. This is new, apparently surprising and counterintuitive. However, at a closer look it fits well with the pathophysiological background and initial preliminary clinical experience available in this important but still largely unexplored field.

Economic, ethical, and environmental sustainability of cardiac imaging.

Current cardiology guidelines assign a class of recommendation 1 for the diagnosis of chest pain to five imaging techniques based on either anatomic (coronary computed tomography angiography) or functional approaches, such as stress single-photon emission tomography, stress positron emission tomography, stress cardiovascular magnetic resonance, and stress echocardiography. The choice is left to the prescribing physician, based on local availability and expertise. However, the five techniques differ substantially in their cost, applicability based on patient characteristics, long-term risk, and environmental impact. The average European immediate cost ranges from 50 to 1000 euros. The radiation exposure ranges from 0 to 500 chest x-rays. The environmental footprint ranges from 3 to 300 kg of carbon dioxide emissions equivalent. The ethical code of the World Medical Association 2021 recommends the responsible use of healthcare money by doctors, with the minimization of potential damage to patients and the environment. The Euratom law 2013/directive 59 reinforces the justification principle and the optimization principle for medical radiation exposures, with the legal responsibility of both the referrer and the practitioner. A small cost, a minimal long-term risk, and a modest carbon emission per examination multiplied by billions of tests per year become an unaffordable economic burden in the short-term, significant population damage to public health over the years, and impacts on climate change in decades. The cardiology community may wish to adopt a more sustainable practice with affordable, radiation-optimized, and carbon-neutral practices for the benefit of patients, physicians, payers, and the planet.

Pulmonary congestion during Exercise stress Echocardiography in Hypertrophic Cardiomyopathy.

BACKGROUND: B-lines detected by lung ultrasound (LUS) during exercise stress echocardiography (ESE), indicating pulmonary congestion, have not been systematically evaluated in patients with hypertrophic cardiomyopathy (HCM). AIM: To assess the clinical, anatomical and functional correlates of pulmonary congestion elicited by exercise in HCM. METHODS: We enrolled 128 HCM patients (age 52 ± 15 years, 72 males) consecutively referred for ESE (treadmill in 46, bicycle in 82 patients) in 10 quality-controlled centers from 7 countries (Belgium, Brazil, Bulgaria, Hungary, Italy, Serbia, Spain). ESE assessment at rest and peak stress included: mitral regurgitation (MR, score from 0 to 3); E/e'; systolic pulmonary arterial pressure (SPAP) and end-diastolic volume (EDV). Change from rest to stress was calculated for each variable. Reduced preload reserve was defined by a decrease in EDV during exercise. B-lines at rest and at peak exercise were assessed by lung ultrasound with the 4-site simplified scan. B-lines positivity was considered if the sum of detected B-lines was ≥ 2. RESULTS: LUS was feasible in all subjects. B-lines were present in 13 patients at rest and in 38 during stress (10 vs 30%, p < 0.0001). When compared to patients without stress B-lines (n = 90), patients with B-lines (n = 38) had higher resting E/e' (14 ± 6 vs. 11 ± 4, p = 0.016) and SPAP (33 ± 10 vs. 27 ± 7 mm Hg p = 0.002). At peak exercise, patients with B-lines had higher peak E/e' (17 ± 6 vs. 13 ± 5 p = 0.003) and stress SPAP (55 ± 18 vs. 40 ± 12 mm Hg p < 0.0001), reduced preload reserve (68 vs. 30%, p = 0.001) and an increase in MR (42 vs. 17%, p = 0.013) compared to patients without congestion. Among baseline parameters, the number of B-lines and SPAP were the only independent predictors of exercise pulmonary congestion. CONCLUSIONS: Two-thirds of HCM patients who develop pulmonary congestion on exercise had no evidence of B-lines at rest. Diastolic impairment and mitral regurgitation were key determinants of pulmonary congestion during ESE. These findings underscore the importance of evaluating hemodynamic stability by physiological stress in HCM, particularly in the presence of unexplained symptoms and functional limitation.

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.

The Role of Stress Echocardiography in Valvular Heart Disease.

PURPOSE OF REVIEW: Stress echocardiography is recommended in valvular heart disease when there is a mismatch between resting transthoracic echocardiography findings and symptoms during activities of daily living. We describe the current methodology and the evidence supporting these applications. RECENT FINDINGS: The comprehensive stress echo assessment includes valve function (gradients and regurgitation), left ventricular global systolic and diastolic function, left atrial volume, pulmonary congestion, pulmonary arterial pressure, and right ventricular function, integrated with blood pressure response with cuff sphygmomanometer, chronotropic reserve with heart rate, and symptoms. Recent guidelines recommend the evaluation of asymptomatic severe or symptomatic non-severe mitral regurgitation or stenosis with exercise stress and suspected low-flow, low-gradient severe aortic stenosis with reduced ejection fraction with low dose (up to 20 mcg, without atropine) dobutamine stress. Prospective, large-scale studies based on a comprehensive protocol (ABCDE +) capturing the multiplicity of clinical phenotypes are needed to support stress echo-driven treatment strategies.

Reduced coronary flow velocity reserve and blunted heart rate reserve identify a higher risk group in patients with chest pain and negative emergency department evaluation.

To estimate the prognostic value of stress echo (SE) with the assessment of coronary flow velocity reserve (CFVR) and heart rate reserve (HRR) in patients admitted for chest pain with non-diagnostic EKG, negative troponin, and without inducible regional wall motion abnormalities (RWMA). 658 patients (age 67 ± 12 years) admitted to our Emergency Department with chest pain, non-diagnostic EKG, and negative serial troponin underwent dipyridamole (0.84 mg/kg in 6') SE with simultaneous assessment of RWMA, CFVR in the left anterior descending artery, and HRR as peak/rest heart rate. The outcome measure was all-cause mortality. Of the 658 patients initially enrolled, 20 (3%) showed RWMA during SE and were referred to ischemia-driven revascularization. In the remaining 638, CFVR was abnormal (≤ 2.0) in 148 patients (23%). HRR was abnormal (≤ 1.22 in patients in sinus rhythm, or ≤ 1.17 in patients with permanent atrial fibrillation) in 196 patients (31%). During a follow-up of 7.3 ± 4.3 years, 151 (24%) patients died. Survival at 8 years was 93% in patients with normal CFVR and HRR, 76% in patients with abnormal CFVR only, 73% in patients with abnormal HRR only, and 38% in those with abnormal CFVR and HRR (p < 0.0001). At multivariable analysis, abnormal CFVR (HR 1.49, 95% CI 1.05-2.10, p = 0.02) and abnormal HRR (HR 2.01, 95% CI 1.43-2.84, p < 0.0001) were independent predictors of survival. In admitted patients with non-ischemic EKG, negative serial troponin, and without RWMA during dipyridamole SE, a reduced CFVR and blunted HRR independently identify a subset with worse survival in the long term. Upper panel: Color and pulsed-wave Doppler with the electrocardiographic lead tracing of Four different response patterns (from left to right): normal CFVR and HRR; normal CFVR, abnormal HRR; abnormal CFVR, normal HRR; abnormal CFVR and HRR. Lower panel: The annualized death rate for each of the four groups with negative SE for RWMA and stratified according to the presence of CFVR and HRR: none, one, or two abnormalities.