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

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 ¼ 1,012), vasodilator (n ¼ 1,054), or dobutamine (n ¼ 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 ¼ 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n ¼ 428; 20%); group III, moderate B-lines (score: 5 to 9; n ¼ 209; 9.7%) and group IV, severe B-lines (score: $10; n ¼ 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 [

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.

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Background The assessment of coronary flow velocity reserve (CFVR) on left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on regional wall motion abnormalities (RWMA). Aim To assess the feasibility and functional correlates of CFVR. Methods In a prospective, observational, multicenter study, we initially screened 3,410 patients (2061, 60%, male; age 63±11 years; ejection fraction, EF=61±9%) with known or suspected coronary artery disease (CAD) and/or heart failure (HF). All patients underwent SE (exercise, n=1288; vasodilator, n=1860; dobutamine, n=262) based on RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. We also assessed B-lines (a sign of pulmonary congestion) with lung ultrasound and left ventricular contractile reserve (LVCR) based on Force (systolic blood pressure/end-systolic volume). Results The success rate for CFVR on LAD was 3,002/3,410 (feasibility=88%): 1,025/1,288 for exercise (80%), 1,766/1,860 (95%) for vasodilator (dipyridamole, n=1,841 and adenosine= 18) and 211/262 (81%) for dobutamine (p<0.001 vs vasodilator, p=NS vs exercise). Imaging time was <3 min and analysis time <1 min per patient. Reduced (≤2.0) CFVR was found in 896/3,002 (30%) patients. At multivariate logistic regression analysis, age (odds ratio, OR: 1.025, 95% Confidence intervals, CI: 1.015–1.036, p<0.001), diabetes (OR: 2.271, 95% CI: 1.218–4.235, p=0.10), RWMA (OR: 6.550, 95% CI: 4.989–8.599, p<0.01), abnormal LVCR (OR: 3.446, 95% CI: 2.774–4.281, p<0.01) and stress-rest B-lines change (OR: 1.519, 95% CI: 1.174–1.99, p=0.01) were associated with reduced CFVR. In the 1149 patients with coronary angiographic information, a reduced CFVR was present in 103/455 patients (23%) with no CAD, 119/432 (27%) with 1-, 72/167 (43%) with 2-, and 62/95 (65%) with 3-vessel disease (p<0.001 by ANOVA for trend). Figure 1 Conclusions CFVR is feasible with all SE protocols. The reduced CFVR is often accompanied by RWMA, abnormal LVCR and pulmonary congestion during stress.

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