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Background: Elective percutaneous coronary intervention (PCI) is performed to relieve symptoms of angina. Identifying patients who will benefit symptomatically after PCI would be clinically advantageous but robust predictors of symptom resolution are ill-defined., Methods: Prospective indexing of baseline angina status, clinical, and procedural characteristics were collected over a 5-year period in a regional revascularization registry. At 1-year follow-up, angina resolution was assessed. We performed a stepwise selection algorithm to identify predictors of persistent angina at 1 year., Results: A total of 777 patients were included in the analysis and the median follow-up was 387 days. Mean age of the cohort was 66.6 years, 23.8% were female and 23.3% had baseline Canadian Cardiovascular Society class 3 or 4 angina. Overall, 13.1% had persistent angina. The only predictor of persistent angina was the presence of a residual chronic total occlusion after PCI with odds ratio of 3.06 (95% confidence interval, 1.81-5.17). Residual stenoses 50-69%, 70-89%, and 90-99% were not associated with residual angina after PCI., Conclusion: Most patients achieved symptom resolution with PCI and optimal medical therapy. A residual chronic total occlusion after PCI was associated with persistent angina. Other degrees of stenoses were not associated with persistent angina., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chest pain remains one of the most challenging serious complaints in the emergency department (ED). A prompt and accurate risk stratification tool for chest pain patients is paramount to help physcian effectively progrnosticate outcomes. HEART score is considered one of the best scores for chest pain risk stratification. However, most validation studies of HEART score were not performed in populations different from those included in the original one., Objective: To validate HEART score as a prognostication tool, among Tunisian ED patients with undifferentiated chest pain., Methods: Our prospective, multicenter study enrolled adult patients presenting with chest pain at chest pain units. Patients over 30 years of age with a primary complaint of chest pain were enrolled. HEART score was calculated for every patient. The primary outcome was major cardiovascular events (MACE) occurrence, including all-cause mortality, non-fatal myocardial infarction (MI), and coronary revascularisation over 30 days following the ED visit. The discriminative power of HEART score was evaluated by the area under the ROC curve. A calibration analysis of the HEART score in this population was performed using Hosmer-Lemeshow goodness of test., Results: We enrolled 3880 patients (age 56.3; 59.5% males). The application of HEART score showed that most patients were in intermediate risk category (55.3%). Within 30 days of ED visit, MACE were reported in 628 (16.2%) patients, with an incidence of 1.2% in the low risk group, 10.8% in the intermediate risk group and 62.4% in the high risk group. The area under receiver operating characteristic curve was 0.87 (95% CI 0.85-0.88). HEART score was not well calibrated (χ 2 statistic = 12.34; p = 0.03)., Conclusion: HEART score showed a good discrimination performance in predicting MACE occurrence at 30 days for Tunisian patients with undifferentiated acute chest pain. Heart score was not well calibrated in our population., (© 2021. The Author(s).)

Background: Complement activation has been associated with atherosclerosis, atherosclerotic plaque destabilization and increased risk of cardiovascular events. Complement component 7 (CC7) binds to the C5bC6 complex which is part of the terminal complement complex (TCC/C5b-9). High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of systemic inflammation and may reflect the increased inflammatory state associated with cardiovascular disease., Aim: To evaluate the associations between CC7 and total- and cardiac mortality in patients hospitalized with chest-pain of suspected coronary origin, and whether combining CC7 with hsCRP adds prognostic information., Methods: Baseline levels of CC7 were related to 60-months survival in a prospective, observational study of 982 patients hospitalized with a suspected acute coronary syndrome (ACS) at 9 hospitals in Salta, Argentina. A cox regression model, adjusting for conventional cardiovascular risk factors, was fitted with all-cause mortality, cardiac death and sudden cardiac death (SCD) as the dependent variables. A similar Norwegian population of 871 patients was applied to test the reproducibility of results in relation to total death., Results: At follow-up, 173 patients (17.7%) in the Argentinean cohort had died, of these 92 (9.4%) were classified as cardiac death and 59 (6.0%) as SCD. In the Norwegian population, a total of 254 patients (30%) died. In multivariable analysis, CC7 was significantly associated with 60-months all-cause mortality [hazard ratio (HR) 1.26 (95% confidence interval (CI), 1.07-1.47) and cardiac death [HR 1.28 (95% CI 1.02-1.60)], but not with SCD. CC7 was only weakly correlated with hsCRP (r = 0.10, p = 0.002), and there was no statistically significant interaction between the two biomarkers in relation to outcome. The significant association of CC7 with total death was reproduced in the Norwegian population., Conclusions: CC7 was significantly associated with all-cause mortality and cardiac death at 60-months follow-up in chest-pain patients with suspected ACS., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01377402, NCT00521976., (© 2021. The Author(s).)

Context: The effects of polycystic ovary syndrome (PCOS) on cardiovascular morbidity and mortality are unclear., Objective: This work aims to establish the relative risk of myocardial infarction (MI), stroke, angina, revascularization, and cardiovascular mortality for women with PCOS., Methods: Data were extracted from the Clinical Practice Research Datalink Aurum database. Patients with PCOS were matched to controls (1:1) by age, body mass index (BMI) category, and primary care practice. The primary outcome was the time to major adverse cardiovascular event (MACE); a composite end point incorporating MI, stroke, angina, revascularization and cardiovascular mortality. Secondary outcomes were the individual MACE end points., Results: Of 219 034 individuals with a diagnosis of PCOS, 174 660 (79.7%) met the eligibility criteria and were matched. Crude rates of the composite end point, MI, stroke, angina, revascularization, and cardiovascular mortality were respectively 82.7, 22.7, 27.4, 32.8, 10.5, and 6.97 per 100 000 patient-years for cases, and 64.3, 15.9, 25.7, 19.8, 7.13, and 7.75 per 100 000 patient-years for controls. In adjusted Cox proportional hazard models (CPHMs), the hazard ratios (HRs) were 1.26 (95% CI, 1.13-1.41), 1.38 (95% CI, 1.11-1.72), 1.60 (95% CI, 1.32-1.94), and 1.50 (95% CI, 1.08-2.07) for the composite outcome, MI, angina, and revascularization, respectively. In a time-dependent CPHM, weight gain (HR 1.01; 1.00-1.01), prior type 2 diabetes mellitus (T2DM) (HR 2.40; 1.76-3.30), and social deprivation (HR 1.53; 1.11-2.11) increased risk of progression to the composite end point., Conclusion: The risk of incident MI, angina, and revascularization is increased in young women with PCOS. Weight and T2DM are potentially modifiable risk factors amenable to intervention., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Elevated levels of high-sensitive cardiac troponin T (hs-cTnT) are linked to poor prognosis among emergency department (ED) patients., Objective: Examine the effect of our ED risk assessment among patients with suspected acute coronary syndrome (ACS) and elevated baseline hs-cTnT levels., Design: Observational cohort study of 16776 ED patients with chest pain or dyspnoea and a hs-cTnT sample analyzed at the time of the ED visit. Of these 1480 patients were sent home with elevated hs-cTnT levels (>14 ng/L)., Methods: Analysis of clinical and laboratory data from the local hospital and data from the National Board of Health and Welfare., Results: Admitted patients had 11% and discharged patients had 1.2% 90-day mortality indicating effective risk assessment of patients with suspected ACS. However, if the suspected ACS patient presented with hs-cTnT between 14 and 22 ng/L, the 90-day mortality was 4.1% among discharged and 6.7% among admitted patients. Among discharged patients, an hs-cTnT level above 14 ng/L was a higher independent risk factor for 90-day mortality (HR 3.3, 95% CI 2.9-3.7, p  < 0.001) than if the patient was triaged as a high-risk patient (HR 1.6, 95% CI 1.1-1.8, p  < 0.001)., Conclusions: Our ED risk assessment was less effective among patients presenting with elevated hs-cTnT levels.

The impact of pre-existing depression on mortality in individuals with established coronary artery disease (CAD) remains unclear. We evaluate the clinical implications of pre-existing depression in patients who underwent percutaneous coronary intervention (PCI). Based on National Health Insurance claims data in Korea, patients without a known history of CAD who underwent PCI between 2013 and 2017 were enrolled. The study population was divided into patients with angina (n = 50,256) or acute myocardial infarction (AMI; n = 40,049). The primary endpoint, defined as all-cause death, was compared between the non-depression and depression groups using propensity score matching analysis. After propensity score matching, there were 4262 and 2346 matched pairs of patients with angina and AMI, respectively. During the follow-up period, there was no significant difference in the incidence of all-cause death in the angina (hazard ratio [HR] of depression, 1.013; 95% confidence interval [CI] 0.893-1.151) and AMI (HR, 0.991; 95% CI 0.865-1.136) groups. However, angina patients less than 65 years of age with depression had higher all-cause mortality (HR, 1.769; 95% CI 1.240-2.525). In Korean patients undergoing PCI, pre-existing depression is not associated with poorer clinical outcomes. However, in younger patients with angina, depression is associated with higher all-cause mortality.

Abstract: Optimal medical therapy (OMT) plays a crucial role in the secondary prevention of established coronary artery disease. The renin-angiotensin system (RAS) is an important target of OMT. However, there is limited evidence on whether there is any difference in the combined effect of OMT according to the classes of RAS blockade [angiotensin-converting enzyme inhibitor (ACEI) vs. angiotensin receptor blocker (ARB)]. Based on the nationwide National Health Insurance database in South Korea, 39,096 patients who received OMT after percutaneous coronary intervention between July 2013 and June 2017 were enrolled. Patients were stratified into either acute myocardial infarction (AMI) or angina cohort and analyzed according to the class of RAS blockade included in OMT at discharge (ACEI vs. ARB). The primary end point was all-cause mortality. The study population had a median follow-up of 2.3 years (interquartile range, 1.3-3.3 years). In the propensity score-matched AMI cohort (8219 pairs), the risk for all-cause mortality was significantly lower in patients with ACEI-based OMT than in those with ARB-based OMT (hazard ratio 0.83 of ACEI, 95% confidence interval 0.73-0.94, P = 0.003). However, in the propensity score-matched angina cohort (6693 pairs), the mortality risk was comparable, regardless of the class of RAS blockade (hazard ratio 1.13, 95 confidence interval 0.99-1.29, P = 0.08). In conclusion, in this nationwide cohort study involving patients receiving OMT after percutaneous coronary intervention, ACEI-based OMT was associated with a significantly lower risk of all-cause mortality in patients with AMI in comparison with ARB, but not in those with angina., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Beta-adrenergic receptor blockers are used in patients with coronary artery disease (CAD) to reduce the harmful effects of excessive adrenergic activation on the heart. However, there is limited evidence regarding the benefit of beta-blockers in the context of contemporary management following percutaneous coronary intervention (PCI). We used the nationwide South Korea National Health Insurance database to identify 87,980 patients with a diagnosis of either acute myocardial infarction (AMI; n = 38,246) or angina pectoris (n = 49,734) who underwent PCI between 2013 and 2017, and survived to be discharged from hospital. Beta-blockers were used in a higher proportion of patients with AMI (80.6%) than those with angina (58.9%). Over a median follow-up of 2.2 years (interquartile range 1.2-3.3 years) with the propensity-score matching analysis, the mortality risk was significantly lower in patients treated with a beta-blocker in the AMI group (HR: 0.78; 95% CI 0.69-0.87; p < 0.001). However, the mortality risk was comparable regardless of beta-blocker use (HR: 1.07; 95% CI 0.98-1.16; p = 0.10) in the angina group. The survival benefit associated with beta-blocker therapy was most significant in the first year after the AMI event.

Cardiovascular randomized controlled trials (RCTs) typically set composite end points as the primary outcome to enhance statistical power. However, influence of individual component end points on overall composite outcomes remains understudied., Methods: We searched MEDLINE for RCTs published in 6 high-impact journals (The Lancet, the New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and the European Heart Journal) from 2011 to 2017. Two-armed, parallel-design cardiovascular RCTs which reported composite outcomes were included. All-cause or cardiovascular mortality, myocardial infarction, heart failure, and stroke were deemed "hard" end points, whereas hospitalization, angina, and revascularization were identified as "soft" end points. Type of outcome (primary or secondary), event rates in treatment and control groups for the composite outcome and of its components according to predefined criteria., Results: Of the 45.8% (316/689) cardiovascular RCTs which used a composite outcome, 79.4% set the composite as the primary outcome. Death was the most common component (89.8%) followed by myocardial infarction (66.1%). About 80% of the trials reported complete data for each component. One hundred forty-seven trials (46.5%) incorporated a "soft" end point as part of their composite. Death contributed the least to the estimate of effects (R 2 change = 0.005) of the composite, whereas revascularization contributed the most (R 2 change = 0.423)., Conclusions: Cardiovascular RCTs frequently use composite end points, which include "soft" end points, as components in nearly 50% of studies. Higher event rates in composite end points may create a misleading interpretation of treatment impact due to large contributions from end points with less clinical significance., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sex differences in clinical characteristics and prognosis of vasospastic angina (VA) have not been well elucidated. This study was performed to investigate sex-specific characteristics and predictors for long-term clinical outcomes in patients with VA., Methods: We analyzed 1838 patients (55 years and 62% male) who were diagnosed with definite (n = 680) or intermediate (n = 1212) VA in ergonovine provocation test from a nation-wide VA registry. The primary study end-point was composite events including cardiac death, acute coronary syndrome, ventricular tachycardia or fibrillation, and atrioventricular block during clinical follow-up., Results: Male patients were younger, and there were more smokers and alcohol drinkers in male patients than in female patients. During the median follow-up period of 760 days (interquartile range, 336-1105 days), there were 73 cases (3.97%) of composite events. There was no sex difference in the occurrence of composite events (log-rank p = 0.649). Concomitant significant (≥ 50%) organic coronary stenosis was associated with worse clinical outcomes in both male (hazard ration [HR], 1.97; 95% confidence interval [CI], 1.01-3.85; p = 0.047) and female (HR, 3.26; 95% CI, 1.07-9.89; p = 0.037) patients. Obesity (body mass index ≥ 25 kg/m 2 ) was associated with better prognosis in female VA patients (HR, 0.22; 95% CI, 0.07-0.68; p = 0.008). Even when only patients with definite diagnosis of VA were considered, there was no significant sex difference in clinical outcomes (log-rank p = 0.876)., Conclusions: In VA patients, there were several different clinical characteristics according to sex; however, long-term clinical outcome was similar between sexes. Significant organic coronary stenosis in both sexes and low body mass index (< 25 kg/m 2 ) in females were associated with worse prognosis in VA patients.

Background: The Braden Scale (BS) is a routine nursing measure used to predict pressure ulcer events; it is recommended as a frailty identification instrument., Objective: We aimed to evaluate the predictive utility of the BS in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention., Methods: We enrolled 2285 patients with AMI from the Retrospective Multicenter Study for Early Evaluation of Acute Chest Pain. The patients were divided into 3 groups (B1, B2, and B3) according to their BS score (≤12 vs 13-14 vs ≥15). The primary endpoint was all-cause death., Results: There were 264 (12.0%) all-cause deaths during the median follow-up period of 10.5 (7.9-14.2) months. In-hospital and midterm mortality and other adverse outcomes increased with decreases in the BS score. The Kaplan-Meier survival analysis showed that patients with a lower BS score had a lower cumulative survival rate (P < .001). The multivariate Cox regression analysis showed that a decreased BS score was an independent predictor for all-cause mortality (B2 vs B1: hazard ratio, 0.610; 95% confidence interval, 0.440-0.846; P = .003; B3 vs B1: hazard ratio, 0.345; 95% confidence interval, 0.241-0.493; P < .001)., Conclusions: The BS at admission may be a useful routine nursing measure to evaluate the prognosis of patients with AMI. The BS may be used to stratify risk at early stages and to identify those who may benefit from further assessment and intervention due to frailty syndrome.

Objective: To determine the impact of ivabradine on outcomes important to patients with angina pectoris caused by coronary artery disease., Methods: We conducted a systematic review. We included randomised clinical trials comparing ivabradine versus placebo or no intervention for patients with angina pectoris due to coronary artery disease published prior to June 2020. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Cochrane methodology, Trial Sequential Analysis, Grading of Recommendations Assessment, Development, and Evaluation, and our eight-step procedure. Primary outcomes were all-cause mortality, serious adverse events and quality of life., Results: We included 47 randomised clinical trials enrolling 35 797 participants. All trials and outcomes were at high risk of bias. Ivabradine compared with control did not have effects when assessing all-cause mortality (risk ratio [RR] 1.04; 95% CI 0.96 to 1.13), quality of life (standardised mean differences -0.05; 95% CI -0.11 to 0.01), cardiovascular mortality (RR 1.07; 95% CI 0.97 to 1.18) and myocardial infarction (RR 1.03; 95% CI 0.91 to 1.16). Ivabradine seemed to increase the risk of serious adverse events after removal of outliers (RR 1.07; 95% CI 1.03 to 1.11) as well as the following adverse events classified as serious: bradycardia, prolonged QT interval, photopsia, atrial fibrillation and hypertension. Ivabradine also increased the risk of non-serious adverse events (RR 1.13; 95% CI 1.11 to 1.16). Ivabradine might have a statistically significant effect when assessing angina frequency (mean difference (MD) 2.06; 95% CI 0.82 to 3.30) and stability (MD 1.48; 95% CI 0.07 to 2.89), but the effect sizes seemed minimal and possibly without any relevance to patients, and we identified several methodological limitations, questioning the validity of these results., Conclusion: Our findings do not support that ivabradine offers significant benefits on patient important outcomes, but rather seems to increase the risk of serious adverse events such as atrial fibrillation and non-serious adverse events. Based on current evidence, guidelines need reassessment and the use of ivabradine for angina pectoris should be reconsidered., Prospero Registration Number: CRD42018112082., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with refractory angina who are suboptimal candidates for further revascularization have improved exercise time, decreased angina frequency, and reduced major adverse cardiac events with intramyocardial delivery of CD34 + cells. However, the effect of CD34 + cell therapy on health care expenditures before and after treatment is unknown. We determined the effect of CD34 + cell therapy on cardiac-related hospital visits and costs during the 12 months following stem cell injection compared with the 12 months prior to injection. Cardiac-related hospital admissions and procedures were retrospectively tabulated for patients enrolled at one site in one of three double-blinded, placebo-controlled CD34 + trials in the 12 months before and after intramyocardial injections of CD34 + cells vs placebo. Fifty-six patients were randomized to CD34 + cell therapy (n = 37) vs placebo (n = 19). Patients randomized to cell therapy experienced 1.57 ± 1.39 cardiac-related hospital visits 12 months before injection, compared with 0.78 ± 1.90 hospital visits 12 months after injection, which was associated with a 62% cost reduction translating to an average savings of $5500 per cell therapy patient. Patients in the placebo group also demonstrated a reduction in cardiac-related hospital events and costs, although to a lesser degree than the CD34 + group. Through 1 January 2019, 24% of CD34 + subjects died at an average of 6.5 ± 2.4 years after enrollment, whereas 47% of placebo patients died at an average of 3.7 ± 1.9 years after enrollment. In conclusion, CD34 + cell therapy for subjects with refractory angina is associated with improved mortality and a reduction in hospital visits and expenditures for cardiac procedures in the year following treatment., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

The effect of statin therapy on reducing adverse cardiovascular events in vasospastic angina (VSA) has been inconsistent. Therefore, we investigated the association between statin therapy and adverse cardiovascular events in a large, prospective VSA cohort. The Variant Angina Korea registry consecutively enrolled 2960 patients suspected VSA. Among them, we included 1713 patients who were diagnosed with VSA based on coronary provocation test. We divided the patients into the statin (n = 744) and no-statin group (n = 914) according to the medication prescribed at discharge. The primary outcome was a composite of cardiac death, acute coronary syndrome, and new-onset life-threatening arrhythmia during a 3-year follow-up period. The primary outcome occurred in 32 patients (4.3%) in the statin and 28 patients (3.1%) in the no-statin group. In Kaplan-Meier analysis before and after propensity score matching, there was no significant difference in the cumulative incidence of primary outcomes between both groups. Multivariate Cox regression analysis demonstrated that the focal type of VSA was independent predictor of primary outcomes, but statin therapy was not. Furthermore, the lack of benefit of statin therapy for primary outcomes was consistently observed across the statin intensity and spasm characteristics. In conclusion, the present study demonstrated that statin therapy did not reduce adverse cardiovascular events in patients with VSA.

Background Despite more than 4 million cardiac noninvasive diagnostic tests (NIT) being performed annually for stable coronary artery disease in the United States, it is unclear whether they are associated with downstream improvements in outcomes when compared with no testing. We sought to determine whether NIT was associated with reduced downstream major adverse cardiovascular events when compared with not testing. Methods and Results We conducted a population-based study of ≈1.5 million patients undergoing chest pain evaluation in Ontario, Canada. Patients were categorized into NIT and no-testing groups. Cause-specific proportional hazards models were used to compare the rate of major adverse cardiovascular events (composite outcome of unstable angina, acute myocardial infarction or cardiovascular mortality and each constituent) between the 2 groups after adjusting for clinically relevant covariates. The rate of the composite outcome was ≈25% lower for patients undergoing noninvasive testing (hazard ratio [HR], 0.77; 95% CI, 0.75-0.79). The benefits of testing were consistent for all 3 constituents of the composite; unstable angina (HR, 0.87; 95% CI, 0.82-0.93 for the NIT versus the no-testing group), myocardial infarction (HR, 0.83; 95% CI, 0.79-0.86 for the NIT versus the no-testing group) and cardiovascular mortality (HR, 0.68; 95% CI, 0.65-0.72 for the NIT versus the no-testing group). Conclusions Our large population-based study reports an ≈25% reduction in major adverse cardiovascular events that was independently associated with NIT in outpatients being evaluated for stable angina. This study demonstrates the prognostic importance of NIT versus no testing on the health of contemporary populations.

Objective: We assessed the diagnostic and prognostic implications of early cardiac magnetic resonance (CMR), CMR-based deformation imaging and conventional risk factors in patients with troponin-positive acute chest pain and non-obstructed coronary arteries., Methods: In total, 255 patients presenting between 2009 and 2019 with troponin-positive acute chest pain and non-obstructed coronary arteries who underwent CMR in ≤7 days were followed for a clinical endpoint of all-cause mortality. Cine movies, T2-weighted and late gadolinium-enhanced images were evaluated to establish a diagnosis of the underlying heart disease. Further CMR analysis, including left ventricular strain, was carried out., Results: CMR (performed at a mean of 2.7 days) provided the diagnosis in 86% of patients (54% myocarditis, 22% myocardial infarction (MI) and 10% Takotsubo syndrome and myocardial contusion (n=1)). The 4-year mortality for a diagnosis of MI, myocarditis, Takotsubo and normal CMR patients was 10.2%, 1.6%, 27.3% and 0%, respectively. We found a strong association between CMR diagnosis and mortality (log-rank: 24, p<0.0001). Takotsubo and MI as the diagnosis, age, hypertension, diabetes, female sex, ejection fraction, stroke volume index and most of the investigated strain parameters were univariate predictors of mortality; however, in the multivariate analysis, only hypertension and circumferential mechanical dispersion measured by strain analysis were independent predictors of mortality., Conclusions: CMR performed in the early phase establishes the proper diagnosis in patients with troponin-positive acute chest pain and non-obstructed coronary arteries and provides additional prognostic factors. This may indicate that CMR could play an additional role in risk stratification in this patient population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The History Electrocardiogram Age Risk factor Troponin (HEART) Pathway and Emergency Department Assessment of Chest pain Score (EDACS) are validated accelerated diagnostic pathways designed to risk stratify patients presenting to the emergency department with chest pain. Data from large multisite prospective studies comparing these accelerated diagnostic pathways are limited., Methods: The HEART Pathway Implementation is a prospective three-site cohort study, which accrued adults with symptoms concerning for acute coronary syndrome. Physicians completed electronic health record HEART Pathway and EDACS risk assessments on participants. Major adverse cardiac events (death, myocardial infarction and coronary revascularisation) at 30 days were determined using electronic health record, insurance claims and death index data. Test characteristics for detection of major adverse cardiac events were calculated for both accelerated diagnostic pathways and McNemar's tests were used for comparisons., Results: 5799 patients presenting to the emergency department were accrued, of which HEART Pathway and EDACS assessments were completed on 4399. Major adverse cardiac events at 30 days occurred in 449/4399 (10.2%). The HEART Pathway identified 38.4% (95% CI 37.0% to 39.9%) of patients as low-risk compared with 58.1% (95% CI 56.6% to 59.6%) identified as low-risk by EDACS (p<0.001). Major adverse cardiac events occurred in 0.4% (95% CI 0.2% to 0.9%) of patients classified as low-risk by the HEART Pathway compared with 1.0% (95% CI 0.7% to 1.5%) of patients identified as low-risk by EDACS (p<0.001). Thus, the HEART Pathway had a negative predictive value of 99.6% (95% CI 99.1% to 99.8%) for major adverse cardiac events compared with a negative predictive value of 99.0% (95% CI 98.5% to 99.3%) for EDACS., Conclusions: EDACS identifies a larger proportion of patients as low-risk than the HEART Pathway, but has a higher missed major adverse cardiac events rate at 30 days. Physicians will need to consider their risk tolerance when deciding whether to adopt the HEART Pathway or EDACS accelerated diagnostic pathway., Trial Registration Number: NCT02056964., Competing Interests: Competing interests: SM also receives research funding/support from Abbott Point of Care, Roche Diagnostics, Siemens, PCORI and NHLBI (1 R01 HL118263-01, L30 HL120008). SM is the Chief Medical Officer for Impathiq Inc. JS receives research funding/support from Abbott Point of Care, Roche Diagnostics and and NHLBI (1 R01 HL118263-01). CM receives research funding/support from Siemens, Abbott Point of Care and 1 R01 HL118263. ACS receives research funding from NHLBI (1 R01 HL118263-01)., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Due to the low prevalence of obstructive coronary artery disease (CAD) in women, stress testing has a relatively low predictive value for this. Additionally, conventional cardiovascular risk scores underestimate risk in women. This study sought to evaluate the role of atherosclerosis assessment using carotid ultrasound (CU) in women attending for stress echocardiography (SE)., Methods: This was a prospective study in which consecutive women with recent-onset suspected angina, who were referred for clinically indicated SE, underwent CU., Results: 415 women (mean age 61±10 years, 29% diabetes mellitus, mean body mass index 28) attending for SE underwent CU. 47 women (11%) had inducible wall motion abnormalities, and carotid disease (CD) was present in 46% (carotid plaque in 41%, carotid intima-media thickness >75th percentile in 15%). Women with CD were older (65 vs 58 years, p<0.001), and more likely to have diabetes (41% vs 21%, p=0.001), hypertension (67% vs 36%, p<0.01) and a higher pretest probability of CAD (59% vs 41%, p<0.001). 40% of women classified as low Framingham risk were found to have evidence of CD.The positive predictive value of SE for flow-limiting CAD was 51%, but with the presence of carotid plaque, this was 71% (p<0.01). Carotid plaque (p=0.004) and ischaemia (p=0.01) were the only independent predictors of >70% angiographic stenosis. In women with ischaemia on SE and no carotid plaque, the negative predictive value for flow-limiting disease was 88%.During a follow-up of 1058±234 days, there were 15 events (defined as all-cause mortality, non-fatal myocardial infarction, heart failure admissions and late coronary revascularisation). Age (HR 1.07 (1.00-1.15), p=0.04), carotid plaque burden (HR 1.65 (1.36-2.00), p<0.001) and ischaemic burden (HR 1.41 (1.18-1.68), p<0.001) were associated with outcome. There was a stepwise increase in events/year from 0.3% when there were no ischaemia and atherosclerosis, 1.1% when there was atherosclerosis and no ischaemia, 2.2% when there was ischaemia and no atherosclerosis and 10% when there were both ischaemia and atherosclerosis (p<0.001)., Conclusion: CU significantly improves the accuracy of SE alone for identifying flow-limiting disease on coronary angiography, and improves risk stratification in women attending for SE, as well identifying a subset of women who may benefit from primary preventative measures., Competing Interests: Competing interests: RS has received speaker fees from Bracco (Italy), Phillips (Netherlands) and Lantheus Medical Imaging., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the association between specific heart diseases and suicide., Design: Nationwide retrospective cohort study., Participants: A total of 7 298 002 individuals (3 640 632 males and 3 657 370 females) aged ≥15 years and living in Denmark during 1980-2016., Main Outcome Measures: Incidence rate ratios (IRR) with 95% confidence intervals. In multivariate analysis, we adjust for sex, period, age group, living status, income level, Charlson Comorbidity Index, psychiatric disorders prior to heart disease and self-harm prior to heart disease., Results: Excess suicide rate ratios were found for following disorders: heart failure (IRR: 1.48; 95% CI: 1.38-1.58); cardiomyopathy (IRR: 1.41; 95% CI: 1.16-1.70); acute myocardial infarction (IRR: 1.28; 95% CI: 1.21-1.36); cardiac arrest with successful resuscitation (IRR: 4.75; 95% CI: 3.57-6.33); atrial fibrillation and flutter (IRR: 1.42; 95% CI: 1.32-1.52); angina pectoris (IRR: 1.19; 95% CI: 1.12-1.26); and ventricular tachycardia (IRR: 1.53; 95% CI: 1.20-1.94). A higher rate of suicide was noted during the first 6 months after the diagnosis of heart failure (IRR: 2.38; 95% CI: 2.04-2.79); acute myocardial infarction (IRR: 2.24; 95% CI: 1.89-2.66); atrial fibrillation and flutter (IRR: 2.70; 95% CI: 2.30-3.18); and angina pectoris (IRR: 1.83; 95% CI: 1.53-2.19) when compared to later., Conclusion: Several specific disorders were found to be associated with elevated rates of suicide. Additionally, we found temporal associations with higher suicide rates in the first time after diagnosis. Our results underscore the importance of being attentive towards psychological distress in individuals with heart disease., (© 2020 The Association for the Publication of the Journal of Internal Medicine.)

Background: The Global Registry of Acute Coronary Events (GRACE) score is recommended for stratifying chest pain. However, there are six formulas used to calculate the GRACE score for different outcomes of acute coronary syndrome (ACS), including death (Dth) or composite of death and myocardial infarction (MI), while in hospital (IH), within 6 months after discharge (OH6m) or from admission to 6 months later (IH6m). We aimed to perform the first comprehensive evaluation and comparison of six GRACE models to predict 30-day major adverse cardiac events (MACEs) in patients with acute chest pain in the emergency department (ED)., Methods: Patients with acute chest pain were consecutively recruited from August 24, 2015 to September 30, 2017 from the EDs of two public hospitals in China. The 30-day MACEs included death, acute myocardial infarction (AMI), emergency revascularization, cardiac arrest and cardiogenic shock. The correlation, calibration, discrimination, reclassification and diagnostic accuracy at certain cutoff values of six GRACE models were evaluated. Comparisons with the History, ECG, Age, Risk Factors, and Troponin (HEART) and Thrombolysis in Myocardial Infarction (TIMI) scores were conducted., Results: A total of 2886 patients were analyzed, with 590 (20.4%) patients experiencing outcomes. The GRACE (IHDthMI), GRACE (IH6mDthMI), GRACE (IHDth), GRACE (IH6mDth), GRACE (OH6mDth) and GRACE (OH6mDthMI) showed positive linear correlations with the actual MACE rates (r ≥ 0.568, P < 0.001). All these models had good calibration (Hosmer-Lemeshow test, P ≥ 0.073) except GRACE (IHDthMI) (P < 0.001). The corresponding C-statistics were 0.83(0.81,0.84), 0.82(0.81,0.83), 0.75(0.73,0.76), 0.73(0.72,0.75), 0.72(0.70,0.73) and 0.70(0.68,0.71), respectively, first two of which were comparable to HEART (0.82, 0.80-0.83) and superior to TIMI (0.71, 0.69-0.73). With a sensitivity ≥95%, GRACE (IHDthMI) ≤81 and GRACE (IH6mDthMI) ≤79 identified 868(30%) and 821(28%) patients as low risk, respectively, which were significantly better than other GRACEs and HEART ≤3(22%). With a specificity ≥95%, GRACE (IHDthMI) > 186 and GRACE (IH6mDthMI) > 161 could recognize 12% and 11% patients as high risk, which were greater than other GRACEs, HEART ≥8(9%) and TIMI ≥5(8%)., Conclusions: In this Chinese setting, certain strengths of GRACE models beyond HEART and TIMI scores were still noteworthy for stratifying chest pain patients. The validation and reasonable application of appropriate GRACE models in the evaluation of undifferentiated chest pain should be recommended.

Background: Chest pain is one of the most common complaints among patients presenting to the emergency department (ED). Causes of chest pain can be benign or life threatening, making accurate risk stratification a critical issue in the ED. In addition to the use of established clinical scores, prior studies have attempted to create predictive models with heart rate variability (HRV). In this study, we proposed heart rate n-variability (HRnV), an alternative representation of beat-to-beat variation in electrocardiogram (ECG), and investigated its association with major adverse cardiac events (MACE) in ED patients with chest pain., Methods: We conducted a retrospective analysis of data collected from the ED of a tertiary hospital in Singapore between September 2010 and July 2015. Patients > 20 years old who presented to the ED with chief complaint of chest pain were conveniently recruited. Five to six-minute single-lead ECGs, demographics, medical history, troponin, and other required variables were collected. We developed the HRnV-Calc software to calculate HRnV parameters. The primary outcome was 30-day MACE, which included all-cause death, acute myocardial infarction, and revascularization. Univariable and multivariable logistic regression analyses were conducted to investigate the association between individual risk factors and the outcome. Receiver operating characteristic (ROC) analysis was performed to compare the HRnV model (based on leave-one-out cross-validation) against other clinical scores in predicting 30-day MACE., Results: A total of 795 patients were included in the analysis, of which 247 (31%) had MACE within 30 days. The MACE group was older, with a higher proportion being male patients. Twenty-one conventional HRV and 115 HRnV parameters were calculated. In univariable analysis, eleven HRV and 48 HRnV parameters were significantly associated with 30-day MACE. The multivariable stepwise logistic regression identified 16 predictors that were strongly associated with MACE outcome; these predictors consisted of one HRV, seven HRnV parameters, troponin, ST segment changes, and several other factors. The HRnV model outperformed several clinical scores in the ROC analysis., Conclusions: The novel HRnV representation demonstrated its value of augmenting HRV and traditional risk factors in designing a robust risk stratification tool for patients with chest pain in the ED.

Background: Triage decisions for chest pain patients receiving usual care are based on a dynamic and comprehensive strategy performed in the physician's mind. It remains controversial whether simple, structured risk tools can surpass real, complex judgments., Hypothesis: The potentially used History, Electrocardiogram, Age, Risk factors, Troponin (HEART) score would help identify low-risk patients for discharge., Methods: Patients with acute, non-traumatic chest pain managed according to usual care were consecutively enrolled in a tertiary university hospital in China from August 24, 2015 to September 30, 2017. Major adverse cardiac events (MACE) included death, acute myocardial infarction, revascularization, and significant coronary stenosis (>50%) within 30 days. We compared the efficacy and safety of usual care and the potentially used HEART score in this population., Results: Of 2185 patients analyzed, 926 (42.4%) patients were directly discharged by usual care, whereas HEART≤3 would have identified 524 (24.0%) patients as low-risk (P < .001). The MACE rate in discharged patients was 2.2% (20/926) and would have been 5.2% (27/524) in those with HEART≤3 (P = .002). For discharged patients, the MACE rates in HEART≤3 vs HEART>3 groups were not significantly different (1.5% vs 2.7%, P = .225). Negative predictive value (NPV) was higher with usual care than with the HEART score (P = .003), but sensitivity was similar. For 340 patients with serial troponins, usual care was superior to the potentially used HEART score in regard to efficacy., Conclusions: At this institution, usual care identified many more patients for discharge than the HEART score would have without apparently different outcomes in discharged patients with lower vs higher HEART scores. The HEART score would not appear to provide helpful risk stratification., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Introduction and Objectives: Individuals with mild to moderately decreased estimated glomerular filtration rate (eGFR=30-59 mL/min/1.73 m 2 ) are considered at high risk of cardiovascular disease (CVD). No studies have compared this risk in eGFR=30-59, diabetes mellitus (DM), and coronary heart disease (CHD) in regions with a low incidence of CHD., Methods: We performed a retrospective cohort study of 122 443 individuals aged 60-84 years from a region with a low CHD incidence with creatinine measured between January 1, 2010 and December 31, 2011. We identified hospital admissions due to CHD (myocardial infarction, angina) or CVD (CHD, stroke, or transient ischemic attack) from electronic medical records up to December 31, 2013. We estimated incidence rates and Cox regression adjusted subdistribution hazard ratio (sHR) including competing risks in patients with eGFR=30-59, DM and CHD, or combinations, compared with individuals without these diseases., Results: The median follow-up was 38.3 [IQR, 33.8-42.7] months. Adjusted sHR for CHD in individuals with eGFR=30-59, DM, eGFR=30-59 plus DM, previous CHD, CHD plus DM, and CHD plus eGFR=30-59 plus DM, were 1.34 (95%CI, 1.04-1.74), 1.61 (95%CI, 1.36-1.90), 1.96 (95%CI, 1.42-2.70), 4.33 (95%CI, 3.58-5.25), 7.05 (5.80-8.58) and 7.72 (5.72-10.41), respectively. The corresponding sHR for CVD were 1.25 (95%CI, 1.06-1.46), 1.56 (95%CI, 1.41-1.74), 1.83 (95%CI, 1.50-2.23), 2.86 (95%CI, 2.48-3.29), 4.54 (95%CI, 3.93-5.24), and 5.33 (95%CI, 4.31-6.60)., Conclusions: In 60- to 84-year-olds with eGFR=30-59, similarly to DM, the likelihood of being admitted to hospital for CHD and CVD was about half that of individuals with established CHD. Thus, eGFR=30-59 does not appear to be a coronary-risk equivalent. Individuals with CHD and DM, or eGFR=30-59 plus DM, should be prioritized for more intensive risk management., (Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery disease., Background: Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease., Methods: A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure-facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life [EQ-5D]) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up., Results: Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p < 0.001). Quality of life (EQ-5D index) improved in the intervention group relative to the control group (mean difference 0.11 units [18%]; 95% confidence interval: 0.03 to 0.19; p = 0.010). After a median follow-up duration of 19 months (interquartile range: 16 to 22 months), major adverse cardiac events were similar between the groups, occurring in 9 subjects (12%) in the intervention group and 8 (11%) in the control group (p = 0.803)., Conclusions: Stratified medical therapy in patients with ischemia and no obstructive coronary artery disease leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography. (Coronary Microvascular Angina [CorMicA]; NCT03193294)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether sex differences exist in the triage, management and outcomes associated with non-traumatic chest pain presentations in the emergency department (ED)., Methods: All adults (≥18 years) with non-traumatic chest pain presentations to three EDs in Melbourne, Australia between 2009 and 2013 were retrospectively analysed. Data sources included routinely collected hospital databases. Triage scoring of the urgency of presentation, time to medical examination, cardiac troponin testing, admission to specialised care units, and in-ED and in-hospital mortality were each modelled using the generalised estimating equations approach., Results: Overall 54 138 patients (48.7% women) presented with chest pain, contributing to 76 216 presentations, of which 26 282 (34.5%) were cardiac. In multivariable analyses, compared with men, women were 18% less likely to be allocated an urgency of 'immediate review' or 'within 10 min review' (OR=0.82, 95% CI 0.79 to 0.85), 16% less likely to be examined within the first hour of arrival to the ED by an emergency physician (0.84, 0.81 to 0.87), 20% less likely to have a troponin test performed (0.80, 0.77 to 0.83), 36% less likely to be admitted to a specialised care unit (0.64, 0.61 to 0.68), and 35% (p=0.039) and 36% (p=0.002) more likely to die in the ED and in the hospital, respectively., Conclusions: In the ED, systemic sex bias, to the detriment of women, exists in the early management and treatment of non-traumatic chest pain. Future studies that identify the drivers explaining why women presenting with chest pain are disadvantaged in terms of care, relative to men, are warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Chest pain in patients without obstructive coronary artery disease has been realized as a frequent problem encountered in clinical practice. Invasive flow investigations have suggested that up to two-thirds of patients with nonobstructive coronary atherosclerosis may have microvascular dysfunction (MVD). Positron emission tomography myocardial perfusion imaging in conjunction with tracer-kinetic modeling enables the concurrent quantification of myocardial blood flow (MBF) in milliliters per minute per gram of tissue. This allows the assessment of hyperemic MBFs and myocardial flow reserve for the noninvasive identification and characterization of MVD as an important functional substrate for angina symptoms amenable to intensified and individualized medical intervention with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, and/or angiotensin II type 1 receptor blockers. Recent investigations suggest that cardiac magnetic resonance and computed tomography may also be suitable for the noninvasive detection of MVD. Whether intensified and individualized treatment related improvement or even normalization of hyperemic MBF and/or myocardial flow reserve may lead to a persistent reduction in angina symptoms and/or improved cardiovascular outcome as compared to standard care, deserves further testing in large-scale randomized clinical trials., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Ranolazine is an anti-angina agent with many metabolites creating the potential for off-target effects. The U.S. Food and Drug Administration (FDA) reviews sometimes contain clinically relevant data not found in other sources., Methods: We reanalyzed data in an FDA review of the placebo-controlled MERLIN trial of ranolazine to display differences in adverse event rates graphically., Results: Rates of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)-related adverse events (eg, angioedema, dry cough, renal impairment, hypotension, anemia, and serum potassium > 5.5 mmol/L) were higher in patients receiving ranolazine and an ACEI or ARB. Rates of adverse events that should be decreased by ACEI/ARBs (eg, hypokalemia, hypertension, and serum potassium < 3.5 mmol/L) were lower in patients receiving ranolazine and an ACEI or ARB compared to rates in patients receiving placebo and an ACEI or ARB., Conclusions: Ranolazine potentiates the effects of ACEIs and ARBs. Clinicians should monitor for this potentiation when initiating treatment with ranolazine and an ACEI or ARB., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives. Coronary revascularisation and intra-aortic balloon pump (IABP) has been considered the gold standard treatment of acute coronary syndrome with cardiogenic shock, recently challenged by the SHOCK II study. The aim of this non-randomised study was to investigate the long term prognosis after immediate IABP supported angiography, in patients with acute chest pain and cardiogenic shock, treated with percutaneous coronary intervention (PCI), cardiac surgery or optimal medical treatment. We assessed data from 281 consecutive patients admitted to our department from 2004 to 2010. Results. Mean (±SD) age was 63.8 ± 11.5 (range 30-84) years with a follow-up of 5.6 ± 4.4 (0-12.7) years. Acute myocardial infarction was the primary diagnosis in 93% of the patients, 4% presented with unstable angina pectoris and 3% cardiomyopathy or arrhythmias of non-ischemic aetiology. Systolic blood pressure at admittance was 85 ± 18 mmHg and diastolic 55 ± 18 mmHg. Thirty day, one- and five-year survival was 71.2%, 67.3% and 57.7%, respectively. PCI was performed immediately in 70%, surgery was done in 17%, and 13% were not eligible for any revascularisation. Independent variables predicting mortality were medical treatment vs revascularisation, out-of-hospital cardiac arrest, and advanced age. Three serious non-fatal complications occurred due to IABP treatment, i.e. 0.001 per treatment day. Conclusions. We report the use of IABP in patients with acute chest pain admitted for angiography. Long-term survival is acceptable and discriminating factors were no revascularisation, out-of-hospital cardiac arrest and age. IABP was safe and feasible and the complication rate was low.

Background: Currently, there are no clinical scores for risk stratification of low-risk patients with chest pain. We aimed to examine the association between mean platelet volume (MPV) and risk for adverse clinical outcomes in patients with chest pain discharged from internal medicine wards following acute coronary syndrome (ACS) rule-out., Patients and Methods: Included were patients who were admitted to internal medicine wards and were discharged following an ACS-rule-out during 2010-2016. The primary endpoint was the composite of all-cause mortality and hospital admission due to ACS at 30-days following hospital discharge., Results: Included in the study were12 440 patients who were divided into three groups according to MPV. The composite endpoint of 30-day all-cause mortality and hospital admission for ACS occurred more frequently among patients with high MPV. Each one-point increase in MPV was associated with an 18% increase in the risk for the composite endpoint (P = 0.02). Considering patients with MPV less than 7.8 fl as the reference group yielded adjusted hazard ratios for the composite endpoint that was significantly higher in patients in the high MPV tertile ( > 8.8 fl) (hazard ratio 1.6; 95% confidence interval = 1.1-2.5; P = 0.04). Each one-point increase in MPV was associated with an 11% increase in the risk for 1-year all-cause mortality (P = 0.01) and a 10% increase in the risk for 1-year ACS (P = 0.04)., Conclusion: We found an independent association between high MPV and the risk of death and ACS among patients with chest pain who were discharged from internal medicine wards following an ACS-rule-out. MPV may be combined in the risk stratification of patients with chest pain.

Objectives: The aim of this study was to quantify sex differences in diagnostic and revascularisation coronary procedures within 1 year of hospitalisation for acute myocardial infarction (AMI) or angina., Design: This is a prospective cohort study. Baseline questionnaire (January 2006-April 2009) data from the Sax Institute's 45 and Up Study were linked to hospitalisation and mortality data (to 30 June 2016) in a time-to-event analysis, treating death as a censoring event., Setting: This was conducted in New South Wales, Australia., Participants: The study included participants aged ≥45 years with no history of ischaemic heart disease (IHD) who were admitted to hospital with a primary diagnosis of AMI (n=4580) or a primary diagnosis of angina or chronic IHD with secondary diagnosis of angina (n=4457)., Outcome Measures: The outcome of this study was coronary angiography and coronary revascularisation with percutaneous coronary intervention or coronary artery bypass graft (PCI/CABG) within 1 year of index admission. Cox regression models compared coronary procedure rates in men and women, adjusting sequentially for age, sociodemographic variables and health characteristics., Results: Among patients with AMI, 71.6% of men (crude rate 3.45/person-year) and 64.7% of women (2.62/person-year) received angiography; 57.8% of men (1.73/person-year) and 37.4% of women (0.77/person-year) received PCI/CABG. Adjusted HRs for men versus women were 1.00 (0.92-1.08) for angiography and 1.51 (1.38-1.67) for PCI/CABG. In the angina group, 67.3% of men (crude rate 2.36/person-year) and 54.9% of women (1.32/person-year) received angiography; 44.6% of men (0.90/person-year) and 19.5% of women (0.26/person-year) received PCI/CABG. Adjusted HRs were 1.24 (1.14-1.34) and 2.44 (2.16-2.75), respectively., Conclusions: Men are more likely than women to receive coronary procedures, particularly revascularisation. This difference is most evident among people with angina, where clinical guidelines are less prescriptive than for AMI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Non-traumatic chest pain (NTCP) is a common reason for emergency department (ED) attendance in high-income countries, with the primary concern focused on life threatening cardiovascular diseases. There is general lack of data on aetiologies, diagnosis and management of NTPC in Sub Sahara African (SSA) countries. We aimed to describe evaluation, diagnosis and outcomes of adult patients presenting with NTCP to an urban ED in Tanzania., Method: This was a prospective observational cohort study of consecutive adult (≥18 years) patients presenting with non-traumatic chest pain to the Emergency Medicine Department (EMD) of Muhimbili National Hospital (MNH) in Dar es salaam from September 2017 to April 2018. Structured case report form was used to collected demographics, clinical presentation, investigations, diagnosis, and EMD disposition and in hospital mortality. We determined frequency of NTCP among our patients, aetiologies, 24-h and 7-day in-hospital mortality, and predictors for mortality., Results: We screened 29,495 adults attending EMD-MNH during the study and 389 (1.3%) presented with NTCP of these, 349 (90%) were enrolled. The median age was 45 (IQR 29-60) years and 177 (50.7%) were female. Overall, 69.1% patients received electrocardiography (ECG) in the EMD and 34.1% had a troponin test. Heart failure and pulmonary tuberculosis (PTB) were the leading hospital diagnoses (12.6% each), followed by chronic kidney disease (10%) and acute coronary syndrome (ACS) (9.6%). Total of 167 (48%) patients were admitted, and the 24-h and 7-day in-hospital mortality were 5 (3%) and 16 (9.6%) respectively. Univariate risk factors for mortality were a Glasgow Coma Scale of < 15 [RR = 3.4 (95%CI 3.2-23)], Acute Coronary Syndrome [RR = 5.7 (95% CI 1.7-11.8) and Troponin > 0.04 ng/ml [RR 2.9 (95%CI 1.2-7.3)]. Features distinguishing cardiovascular from other causes were: bradycardia [RR = 2.6 (95%CI 2.1-3.2)], heart beat awareness [RR = 2.3 (95%CI 1.7-3.2)] and history of diabetic mellitus [RR = 2.2 (95% CI 1.6-3.0)]., Conclusion: In this ED of SSA country, heart failure and pulmonary tuberculosis were the leading causes of NCTP, and ACS was present in 9.6%. NTCP in this setting carries high mortality, and ACS was the leading risk factor for death. ED providers in SSA must increasingly consider cardiovascular causes of NTCP.

Background: Coronary heart disease angina is a very common cardiovascular disease, which not only causes personal health problems, but also a serious burden on the social economy. Xuefu Zhuyu Decoction (XFZYD) has been widely adapted to clinical practice for people with coronary heart disease angina. At present, it is necessary to update the existing research, re-evaluate the effectiveness and safety of XFZYD, and provide the latest evidence for coronary heart disease angina., Methods and Analysis: The purpose of this study was to search the electronic database for XFZYD in the treatment of coronary heart disease angina. The database includes PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure database (CNKI), Wanfang database, Chinese Biomedical Literature database (CBM), Chinese Scientific Journal database (VIP). In addition, ongoing trials will be retrieved from the WHO ICTRP Search Portal, the Chinese Clinical Trial Register and The Clinical Trials Register. We will assess all the documents from the database establishment to January 31, 2019. The RevMan V.5.3 software will be used to calculate the data synthesis and perform a meta-analysis when the literature is appropriate., Results: The study will provide a high-quality synthesis of current evidence of XFZYD for coronary heart disease angina from the various comprehensive assessment, including Significantly effective, Effective, Invalid, Aggravation, which based on the "Guidelines for Clinical Research of New Chinese Medicine". Adverse events are also included., Conclusion: The systematic review will provide evidence for assessing the effectiveness and safety of XFZYD in the treatment of coronary heart disease angina., Prospero Registration Number: PROSPERO CRD42019122003.

Background: Previous studies have demonstrated that intramyocardial human CD34+ cells may relieve symptoms and improve clinical outcomes in chronic refractory angina unresponsive to optimal medical therapy or not amenable to revascularization., Methods: We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of human CD34+ cells compared with placebo in chronic refractory angina. Primary efficacy outcomes in our analysis were angina frequency and exercise time. Primary safety outcomes included major adverse cardiovascular events such as myocardial infarction (MI), stroke and death., Results: Three eligible randomized trials including 269 patients (placebo = 90, CD34+ = 179) were included. Dose of auto-CD34+ cells ranged from 5 × 10 4 to 5 × 10 5  cells/kg. Follow-up ranged from 6 to 24 months. In a pooled analysis, administration of CD34+ cells decreased the risk of all-cause mortality [OR 0.24, 95% CI (0.08-0.73), p = 0.01], reduced angina frequency [mean difference -2.91, 95% CI (-4.57 to -1.25), p = 0.0006] and improved exercise time [mean difference 58.62 s, 95% CI (21.19 to 96.06), p = 0.02] compared with control group. However, there was no significant difference in the risk of myocardial infarction (MI) and stroke between groups., Conclusion: In a meta-analysis, intra-myocardial CD34+ cell therapy was superior to placebo in improving risk of all - cause mortality, angina frequency with an increase in exercise time, without a significant increase in adverse events. This analysis supports further trials of CD34+ cell therapy for ischemic heart disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Aims: Since clinical characteristics and prognosis of patients with multi-vessel vasospastic angina (VSA) are not clear, we investigated the nature and prognosis of multi-vessel VSA in Koreans., Methods: Among 2960 patients enrolled in the VA-KOREA (Vasospastic Angina in Korea) registry, 104 definite multi-vessel VSA patients, 163 single vessel VSA patients and 737 non-VSA patients were identified using the intracoronary ergonovine provocation test., Results: Multi-vessel VSA and single vessel VSA groups showed similar baseline characteristics and medical treatment on discharge, but different from the non-VSA group. The primary composite endpoint (cardiac death, acute coronary syndrome, and symptomatic new onset arrhythmia) over a 36-month follow-up period was significantly higher in the multi-vessel VSA group than in the single vessel VSA and non-VSA groups (8.7% vs. 1.8% and 1.1%, each log-rank p < 0.05, respectively). The rate of death and acute coronary syndrome of the multi-vessel VSA group was higher than in the single vessel VSA and non-VSA groups (5.8% vs. 1.2% and 0.9%, each log-rank p < 0.05, respectively). In addition, multi-vessel VSA was an independent predictor of the primary composite endpoint at 36 months (HR 8.5, 95% CI [2.6-27.2], p < 0.0001)., Conclusions: Patients with multi-vessel VSA had worse clinical outcomes than single vessel VSA and non-VSA groups, suggesting that the existence of multi-vessel VSA itself is highly prognostic., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Object: The purpose of this study was to fully assess the role of statins in the primary prevention of coronary heart disease (CHD)., Methods: We searched six databases (PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database) to identify relevant randomized controlled trials (RCTs) from inception to 31 October 2017. Two review authors independently assessed the methodological quality and analysed the data using Rev Man 5.3 software. Risk ratios and 95% confidence intervals (95% CI) were pooled using fixed/random-effects models. Funnel plots and Begg's test were conducted to assess publication bias. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Results: Sixteen RCTs with 69159 participants were included in this review. Statins can effectively decrease the occurrence of angina (RR=0.70, 95% CI: 0.58~0.85, I 2 =0%), nonfatal myocardial infarction (MI) (RR=0.60, 95% CI: 0.51~0.69, I 2 =14%), fatal MI (RR=0.49, 95% CI: 0.24~0.98, I 2 =0%), any MI (RR=0.53, 95% CI: 0.42~0.67, I 2 =0%), any coronary heart events (RR=0.73, 95% CI: 0.68~0.78, I 2 =0%), coronary revascularization (RR=0.66, 95% CI: 0.55~0.78, I 2 = 0%), and any cardiovascular events (RR=0.77, 95% CI: 0.72~82, I 2 = 0%). However, based on the current evidence, there were no significant differences in CHD deaths (RR=0.82, 95% CI: 0.66~1.02, I 2 =0%) and all-cause mortality (RR=0.88, 95% CI: 0.76 ~1.01, I 2 =58%) between the two groups. Additionally, statins were more likely to result in diabetes (RR=1.21, 95% CI: 1.05~1.39, I 2 =0%). There was no evidence of publication biases, and the quality of the evidence was considered moderate., Conclusion: Statins seemed to be beneficial for the primary prevention of CHDs but have no effect on CHD death and all-cause mortality.

Background: To investigate the early diagnostic and prognostic value of microRNA-1 in patients with acute chest pain., Methods: This study enrolled 341 patients attacked by chest pain within 3 h, and another 100 volunteers as control group. Circulating microRNA-1 was collected and determined by real-time quantitative reverse transcription-polymerase chain reaction. The clinical follow-up period was 720 days., Results: There were 174 patients in acute myocardial infarction (AMI) group, 167 in non-AMI group. The relative expression of microRNA-1 was significantly increased within 3 h in AMI group, and it continued rising within 12 h, lower at 24 h than that 12 h in AMI group without reperfusion therapy. Otherwise, microRNA-1 concentration was markedly low at 12 h after primary percutaneous coronary intervention in AMI group. The 95% reference range of circulating microRNA-1 was 0.171-0.653. It was significantly available for microRNA-1 to early diagnose AMI with an optimal cutoff value of 2.215 and diagnostic accuracy could be improved when combined with cardiac troponin I. It was not statistically significant for microRNA-1 to forecast future AMI but might prognose mortality of 720 days in chest pain patients. In patients with chest pain, microRNA-1 concentration was high with major adverse cardiac events within 30 days, low with high overall survival within 720 days., Conclusions: Circulating microRNA-1 might diagnose early AMI and predict the prognosis of patients with chest pain.

A cohort analysis using UK Clinical Practice Research Datalink (CPRD) was performed to compare the effects of bisoprolol, other β-blockers, and drugs other than β-blockers on the long-term risk of mortality and cardiovascular events in patients with angina. Adult patients first diagnosed with angina from 2000 to 2014, with ≥365 days of registration to first angina diagnosis and initiating monotherapies of bisoprolol, other β-blockers, or drugs other than β-blockers within 6 months of angina diagnosis were included. Incidence rates for each treatment cohort were compared using adjusted hazard ratio (HR) and 95% confidence intervals (CI) obtained from Cox regression analyses. Overall, 987 patients were treated with bisoprolol, 1348 with other β-blockers and 5272 with drugs other than β-blockers. Over the total follow-up (≤14 years), the HR of bisoprolol versus other β-blockers and drugs other than β-blockers for mortality was 0.45 (95% CI: 0.34-0.61) and 0.50 (95% CI: 0.38-0.66), respectively. The HR of bisoprolol versus other β-blockers for angina was 0.58 (95% CI: 0.50-0.68) and versus drugs other than β-blockers was 0.77 (95% CI: 0.68-0.88), respectively. For myocardial infarction, the HR of bisoprolol versus drugs other than β-blockers up to 14 years was 0.34 (95% CI: 0.23-0.52) and versus other β-blockers up to 5 years was 0.45 (95% CI: 0.27-0.75). At 5 years, the HR of bisoprolol versus other β-blockers, and drugs other than β-blockers, for arrhythmia was 0.60 (95% CI: 0.35-1.0) and 0.61 (95% CI: 0.40-0.93), respectively. In conclusion, long-term significant reduction in the risk of mortality and various cardiovascular events with bisoprolol versus other β-blockers, and drugs other than β-blockers, confirm treatment guidelines recommendation that bisoprolol is particularly well suited as the first-line treatment of angina in primary care., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: A significant proportion of patients with complex, advanced coronary artery disease have refractory angina (RA) despite maximal pharmacological therapy and are deemed suboptimal candidates for revascularization. These patients are frequently termed "no-option" patients. However, despite this designation, many subsequently undergo coronary revascularization. We sought to determine the incidence, etiology and outcome of revascularization in "no-option" patients., Methods and Results: We examined a comprehensive, prospective RA database to identify 342 of 1363 (25.1%) patients who subsequently underwent revascularization after a median interval of 2.2 years from the "no-option" diagnosis. Coronary revascularization was achieved by percutaneous coronary intervention (PCI) (n = 274, 20.1%), coronary bypass graft surgery (n = 44, 3.2%) or both (n = 24, 1.8%). During a median follow-up of 5.1 years, patients who underwent revascularization had lower annual mortality (2% vs. 4.4%, P < .001). Detailed paired angiographic records were available for 181 PCI patients with a combined 302 lesions. Of these interventions, 48% were for a new lesion, 31% for an existing lesion and 21% for restenosis. The location was a native vessel in 77% and a bypass graft in 23%., Conclusions: The "no-option" or non-revascularizable designation is frequently based on angiography at a single time-point. However, coronary artery disease is a progressive and dynamic process and new lesions often develop in such patients. Given the association between revascularization and better survival, careful consideration should be given to repeat revascularization in patients with refractory angina previously classified as "no-option"., (© 2018 Wiley Periodicals, Inc.)

Background: To decrease the morbidity burden of cardiovascular disease and to avoid the development of potentially preventable complications, early assessment and treatment of acute coronary syndrome (ACS) are important. The aim of this study has therefore been to explore the possible association between patients' estimated intensity of chest pain when first seen by the ambulance crew in suspected ACS, and the subsequent outcome before and after arrival in hospital., Methods: Data was collected both prospectively and retrospectively. The inclusion criteria were chest pain raising suspicion of ACS and a reported intensity of pain ≥4 on the visual analogue scale., Results: All in all, 1603 patients were included in the study. Increased intensity of chest pain was related to: 1) more heart-related complications before hospital admission; 2) a higher proportion of heart failure, anxiety and chest pain after hospital admission; 3) a higher proportion of acute myocardial infarction and 4) a prolonged hospitalisation. However, there was no significant association with mortality neither in 30 days nor in three years. Adjustment for possible confounders including age, a history of smoking and heart failure showed similar results., Conclusion: The estimated intensity of chest pain reported by the patients on admission by the ambulance team was associated with the risk of complications prior to hospital admission, heart failure, anxiety and chest pain after hospital admission, the final diagnosis and the number of days in hospital., Trial Registration: ClinicalTrials.gov 151:2008/4564 Identifier: NCT00792181. Registred 17 November 2008 'retrospectively registered'.

Background: A fractional flow reserve (FFR) between 0.75 and 0.80 constitutes a "gray zone" for clinical decision-making in coronary artery disease. We compared long-term outcomes of percutaneous coronary intervention (PCI) using drug-eluting stents vs. medical therapy for coronary stenosis with gray zone FFR. Methods and Results: We retrospectively investigated the clinical outcomes of 263 patients with gray zone FFR: 78 patients in the PCI group and 185 patients in the medical therapy group. During a median follow-up of 3.7 years, the frequency of target vessel failure (TVF, defined as a composite of cardiac death, myocardial infarction [MI], or ischemia-driven target vessel revascularization [TVR]) was significantly lower in the PCI group compared with the medical therapy group (6% vs. 19%, hazard ratio [HR]:0.33, 95% confidence interval [CI]: 0.13-0.84, P=0.008). The frequency of a composite of cardiac death or MI was not different between the 2 groups (1% vs. 2%, HR: 0.61, 95% CI: 0.07-5.49, P=0.645). The frequency of ischemia-driven TVR was significantly lower in the PCI group compared with the medical therapy group (5% vs. 18%, HR: 0.28, 95% CI: 0.10-0.79, P=0.005)., Conclusions: In patients with gray zone FFR, compared with medical therapy, PCI decreased the frequency of TVF, which was mainly driven by a reduction in the frequency of angina or myocardial ischemia without any difference in the frequency of cardiac death or MI.

Objectives: The authors sought to perform a randomized controlled trial to evaluate the clinical efficacy of combined examination with coronary computed tomography angiography (CTA) and computed tomography perfusion imaging (CTP) compared to coronary CTA alone., Background: Stress myocardial CTP may increase diagnostic specificity when added to coronary CTA in patients suspected of having ischemic heart disease., Methods: Patients recently hospitalized for acute-onset chest pain, who had acute coronary syndrome had been ruled out by normal electrocardiograms, normal troponin levels, and relief of symptoms, and who had a clinical indication for outpatient noninvasive testing, were screened for inclusion in the CATCH-2 (CArdiac cT in the treatment of acute CHest pain 2) trial (NCT02014311). Patients were randomized 1:1 to examination with coronary CTA or coronary CTA+CTP. The primary endpoint was the frequency of coronary revascularization among patients referred for invasive coronary angiography (ICA) based on index computed tomography evaluation. Secondary endpoints were invasive procedural complications at index-related ICA, post-index cardiac death, hospital admittance because of recurrence of chest pain, unstable angina pectoris, or acute myocardial infarction, ICA, and revascularization., Results: Among 300 patients allocated to the coronary CTA+CTP group, 41 (14%) were referred for ICA compared with 89 (30%) allocated to coronary CTA (p < 0.0001). The primary endpoint occurred in 50% of coronary CTA+CTP patients versus 48% of invasively examined patients (p = 0.85). The total number of revascularizations was significantly lower in the coronary CTA+CTP group compared to the coronary CTA group (n = 20 [7%] vs. n = 42 [14%]; p = 0.0045). At median follow-up of 1.5 years, the occurrence of secondary endpoints was similar in the 2 groups., Conclusions: A post-discharge diagnostic strategy of coronary CTA+CTP safely reduces the need for invasive examination and treatment in patients suspected of having ischemic heart disease. (CArdiac cT in the treatment of acute CHest pain 2-Myocardial CT Perfusion [CATCH2]; NCT02014311)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Data from previous studies of patients with heart failure and coronary artery disease suggest that those with higher resting heart rates (HRs) have worse cardiovascular outcomes. We sought to evaluate whether HR immediately before percutaneous coronary intervention (PCI) is an independent predictor for 30-day outcome. We analyzed the outcome of 3,720 patients who had HR recorded before PCI from the Melbourne Interventional Group registry. HR and outcomes were analyzed by quintiles, and secondarily by dichotomizing into <70 or ≥70 beats/min. Patients with cardiogenic shock, intra-aortic balloon pump or inotropic support, and out-of-hospital arrest were excluded. The mean ± SD HR was 70.9 ± 14.7 beats/min. HR by quintile was 55 ± 5, 64 ± 2, 70 ± 1, 77 ± 3, and 93 ± 13 beats/min, respectively. Patients with higher HR were more likely to be women, current smokers, have higher systolic and diastolic blood pressure, atrial fibrillation, recent heart failure, lower ejection fraction, and ST-elevation myocardial infarction as the indication for the PCI (all p ≤0.002). However, rates of treated hypertension, multivessel disease, previous myocardial infarction, PCI, and coronary bypass surgery were lower (all p ≤0.004). Increased HR was associated with higher 30-day mortality (p for trend = 0.04), target vessel revascularization (p for trend = 0.003), and 30-day major adverse cardiac events (MACE) (p for trend = 0.004). In a multivariable analysis, HR was an independent predictor of 30-day MACE (OR 1.21 per quintile; 95% confidence interval (CI): 1.06 to 1.39, p = 0.004). When dichotomized into <70 or ≥70 beats/min, HR independently predicted both 30-day MACE (OR 1.59, 95% CI 1.08 to 2.36, p = 0.02) and 30-day mortality (OR 2.80, 95% CI 1.10 to 7.08, p = 0.03). In conclusion, HR immediately before PCI is an independent predictor of adverse 30-day cardiovascular outcomes., (Copyright © 2018. Published by Elsevier Inc.)

We sought to investigate the prognostic significance of prodromal angina (PA) in unselected patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and its additive predictive value to the GRACE score.We prospectively enrolled 3015 consecutive STEMI patients undergoing PPCI. Patients were divided in 2 groups according to the presence or absence of PA. Multivariable Cox regression was used to establish the relation to 2-year cardiac mortality of PA.The mean age of the study population was 68 (±14) years; 2178 patients (72%) were male. During follow-up, 395 (13%) patients died with 278 of these (9.2%) suffering from cardiac mortality. Kaplan-Meier estimates showed a survival rate of 95% and 87% for patients with PA and no PA, respectively (log rank test < 0.001). After multivariable analysis, patients with PA had still a lower risk of 2 years' cardiac mortality compared with patients without PA (adjusted hazard ratio = 0.50; 95% confidence interval [CI] 1.06-1.81, P = .001). Evaluation of net reclassification improvement showed that reclassification improved by 0.16% in case patients, whereas classification worsened in control patients by 1.08% leading to a net reclassification improvement of -0.93% (95% CI: -0.98, -0.88).In patients with STEMI undergoing PPCI the presence of PA is independently associated with a lower risk of 2-year cardiac mortality. However, the incorporation of this variable to the GRACE score slightly worsened the classification of risk. Accordingly, it seems unlikely that the evaluation of PA may be useful in clinical practice.