Search

Background The COVID-19 pandemic has had diverse effects on population health and psychology in relation to non-COVID-19 diseases, as well as on COVID-19 infection. Fewer patients with acute myocardial infarction (AMI) sought medical attention during the first lockdown of the pandemic. Methods and results We conducted a retrospective cohort study of Clalit Health Services patients treated in multiple hospitals for AMI. We examined the numbers and characteristics of the patients and 30-day mortality during three 5-week phases of the first wave of the COVID-19 pandemic in Israel: pre-lockdown ( N = 702), lockdown (N = 584), and lockdown-lift (N = 669). We compared data for the same period in 2018 and 2019. We stratified the data by ST-elevation myocardial infarction (STEMI) and non-STEMI. AMI hospitalizations during the lockdown were 17% lower than in the pre-lockdown period (rate ratio-0.83, 95% CI 0.74–0.93), and 22% and 31% lower than in the corresponding periods in 2018 and 2019, respectively. The reduction was mainly attributed to non-STEMI hospitalizations (26% lower than the pre-lockdown period in 2020). Hospitalizations due to both STEMI and non-STEMI were moderately reduced during the post-lockdown period compared to the corresponding periods in 2018 and 2019. Thirty-day mortality rate was similar for all the periods assessed. Conclusions The number of hospitalized patients with AMI during the first COVID-19 lockdown and post-lockdown periods was significantly reduced, without significant changes in 30-day mortality rates.

Background Currently, there is a paucity of data concerning the safety and effectiveness of P2Y12 inhibitors in the acute coronary syndrome (ACS) with chronic kidney disease (CKD) population. The aim of this study is to compare the different oral P2Y12 inhibitors in terms of efficacy and safety, focusing exclusively on patients with CKD who were treated for ACS. Methods We systematically searched PubMed, CENTRAL, and Web of Science to identify studies that compared different oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) in patients with ACS with CKD. Efficacy outcomes included the major adverse cardiovascular events composite outcome and safety outcomes included major bleedings and major or minor bleedings combined. We performed a frequentist network meta-analysis. Results Twelve studies were included in the systematic review, 7 CKD subgroup analyses of RCTs (8878 patients) and 5 observational studies (20175 patients). After the exclusion of studies with conservative management, prasugrel resulted in significant primary endpoint reduction versus clopidogrel (HR 0.80 and 95% CI 0.64 - 0.99), while ticagrelor did not (HR 0.88 and 95% CI 0.73 - 1.06). Major bleedings did not differ between the interventions. Ticagrelor resulted in more major or minor bleedings than clopidogrel (HR 1.21 and 95% CI 1.06 - 1.38), whereas prasugrel did not (HR 1.12 and 95% CI 0.84 - 1.49). Conclusion In patients with ACS with underlying CKD, who are intended to receive invasive management, there may be a significant reduction of the primary efficacy outcome with prasugrel as compared to clopidogrel but not with ticagrelor as compared to clopidogrel. There probably exists no difference among interventions in the major bleedings. Dedicated RCTs are needed to confirm these results.

Mechanical stress from haemodynamic perturbations or interventional manipulation of epicardial coronary atherosclerotic plaques with inflammatory destabilization can release particulate debris, thrombotic material and soluble substances into the coronary circulation. The physical material obstructs the coronary microcirculation, whereas the soluble substances induce endothelial dysfunction and facilitate vasoconstriction. Coronary microvascular obstruction and dysfunction result in patchy microinfarcts accompanied by an inflammatory reaction, both of which contribute to progressive myocardial contractile dysfunction. In clinical studies, the benefit of protection devices to retrieve atherothrombotic debris during percutaneous coronary interventions has been modest, and the treatment of microembolization has mostly relied on antiplatelet and vasodilator agents. The past 25 years have witnessed a relative proportional increase in non-ST-segment elevation myocardial infarction in the presentation of acute coronary syndromes. An associated increase in the incidence of plaque erosion rather than rupture has also been recognized as a key mechanism in the past decade. We propose that coronary microembolization is a decisive link between plaque erosion at the culprit lesion and the manifestation of non-ST-segment elevation myocardial infarction. In this Review, we characterize the features and mechanisms of coronary microembolization and discuss the clinical trials of drugs and devices for prevention and treatment., In this Review, Kleinbongard and Heusch characterize the features and mechanisms of coronary microembolization and discuss the clinical trials of drugs and devices for the prevention and treatment of this phenomenon., Key points Coronary microembolization results from spontaneous or interventional erosion or rupture of an epicardial coronary atherosclerotic plaque.Atherothrombotic plaque debris causes physical obstruction of coronary microvessels and results in microinfarcts with an inflammatory response.The surviving myocardium around the patchy microinfarcts has reduced contractile function as a result of inflammatory signal transduction leading to myofibrillar oxidation.Atherosclerotic plaque erosion or rupture releases soluble substances that induce coronary microvascular endothelial dysfunction, vasoconstriction, platelet aggregation and coagulation.Routine use of interventional protection devices does not improve patient outcomes but these devices are indicated in cases of high atherothrombotic plaque burden.Plaque stabilization with statins and canakinumab prevents coronary microembolization, whereas platelet inhibitors, vasodilators and interleukin antagonists attenuate coronary microvascular impairment.

Limited evidence is available on apparent temperature (AT) and hospital admissions for acute cardiac events. We examined the associations of AT with admissions for acute cardiac events and acute coronary syndrome (ACS), and explored the effect difference between ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction ACS (NSTE-ACS). Poisson regression with distributed lag non-linear model was applied to examine the temperature-lag-admission associations. Stratified analyses were performed by gender and age-groups for acute cardiac events. A total of 11,657 acute cardiac events admissions were collected from hospital-based chest pain centers in Beijing, during 2017–2019. The single day effect of low AT (− 11 °C, 2.5th percentile) appeared on the 2nd day and persisted until the 11th day, with estimated relative risk (RR) ranging from 1.44 (95% CI: 1.159, 1.790) to 1.084 (95% CI: 1.022, 1.150) for acute cardiac events and from 1.034 (95% CI: 1.010, 1.059) to 1.006 (95% CI: 1.000, 1.011) for ACS. The single day effect of high AT (34 °C, 97.5th percentile) was only observed on the current day. The cold effect on acute cardiac events was more pronounced among female and older patients. The cumulative effect of high AT on STEMI admissions and low AT on NSTE-ACS reached a peak RR peak of 2.545 (95% CI: 1.016, 6.375) and 3.71 (95% CI: 1.315, 10.469) on lag 0–6 days, respectively. Both high and low ATs were associated with increased risk of acute cardiac events and ACS admissions. STEMI admissions may be more sensitive to high AT while NSTE-ACS to low AT.

Coronary heart disease (CHD) is the result of a complex metabolic disorder caused by various environmental and genetic factors, and often has anxiety as a comorbidity. Rupture of atherosclerotic plaque in CHD patients can lead to acute coronary syndrome (ACS). Anxiety is a known independent risk factor for the adverse cardiovascular events and mortality in ACS, but it remains unclear how stress-induced anxiety behavior impacts their blood plasma metabolome and contributes to worsening of CHD. The present study aimed to determine the effect of anxiety on the plasma metabolome in ACS patients. After receiving ethical approval 26 ACS patients comorbid anxiety were recruited and matched 26 ACS patients. Blood plasma samples were collected from the patients and stored at − 80 °C until metabolome profiling. Metabolome analysis was performed by liquid chromatography mass spectrometry (LC–MS), and the data were subjected to multivariate analysis. Disturbance of 39 plasma metabolites was noted in the ACS with comorbid anxiety group compared to the ACS group. These disturbed metabolites were mainly involved in tryptophan metabolism, pyrimidine metabolism, glycerophospholipid metabolism, pentose phosphate pathway, and pentose and glucuronate interconversions. The most significantly affected pathway was tryptophan metabolism including the down-regulation of tryptophan and serotonin. Glycerophospholipids metabolism, pentose and glucuronate interconversions, and pentose phosphate pathway were also greatly affected. These results suggest that anxiety can disturb three translation of material in ACS patients. Besides the above metabolism pathways pyrimidine metabolism was significantly disturbed. Based on the present findings the plasma metabolites monitoring can be recommended and may be conducive to early biomarkers detection for personalized treatment anxiety in CHD patients in future.

©The European Society of Cardiology 2020. Article reuse guidelines : sagepub.com/journals-permissions, Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and ‘modern’ cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.

The pathophysiology of acute coronary syndromes was thought to be coronary thrombosis over a plaque rupture. Autopsy studies revealed that not all cases were due to plaque rupture, even denuded endothelium or calcific nodule can beget a thrombus. Introduction of OCT made, in vivo recognition of lesion morphology clear. Plaque ruptures are most common and need primary angioplasty. Recent studies established plaque erosion is responsible for ACS in one third of the cases and majority of them present as Non ST elevation myocardial infarction and commonly found in young patients without major risk factors. Evidence from recent studies suggested that stenting can be deferred and they can be managed conservatively with good long term outcomes. More randomized trials are needed comparing plaque rupture and plaque erosion as regards conservative versus invasive management. If these studies substantiate the concept of conservative management, it will lead to a paradigm shift in their management.

Background Cardiovascular disease contributes to a massive mortality rate in the world and also in Indonesia. Assessment of the risk and level of knowledge of cardiac emergency symptoms needs to be carried out, especially in rural areas where access to cardiovascular treatment is far.Purposes This study aims to assess risk stratification and the level of knowledge. The method of measuring risk and level of knowledge was carried out on 100 Margasari Ilir respondent who were over 40 years old and carried out using the stratified random sampling method during September 2020—measuring risk using the instrument Framingham Risk Score and the level of knowledge using the ACS Response Index.Result The average age of respondents was 54.98 years, 30 men (30%) and 70 women (70%), 22 smokers (22%), seven diabetes mellitus (7%), 11 people ( 11%) had high cholesterol, 41 people (41%) had hypertension, and 33 people (33%) had low HDL levels. The number of people who have a high risk of emergency - cardiovascular emergency is seven people (7%), 24 people are at moderate risk (24%), and 69 people are at low risk (69%). The level of knowledge about cardiac emergencies is in the low category of 80 people (80%), 19 people (19%), and one high (1%).Conclusion It is necessary to increase public knowledge about cardiovascular emergencies.

Multiple new recommendations have been introduced in the 2020 ESC guidelines for the management of acute coronary syndromes with a focus on diagnosis, prognosis, and management of patients presenting without persistent ST-segment elevation. Most recommendations are supported by high-quality scientific evidence. The guidelines provide solutions to overcome obstacles presumed to complicate a convenient interpretation of troponin results such as age-, or sex-specific cutoffs, and to give practical advice to overcome delays of laboratory reporting. However, in some areas, scientific support is less well documented or even missing, and other areas are covered rather by expert opinion or subjective recommendations. We aim to provide a critical appraisal on several recommendations, mainly related to the diagnostic and prognostic assessment, highlighting the discrepancies between Guideline recommendations and the existing scientific evidence.

The risk of ischemic events carried by different clusters of type 2 diabetes mellitus (DM) in the setting of secondary prevention is not definite and the association between DM and bleeding complications is controversial. We explored these issues in the START-ANTIPLATELET, a multicenter Italian registry including acute coronary syndrome (ACS) patients. Study outcome was 1-year incidence of the net composite endpoint including major adverse cardiovascular events (MACE) or any bleeding and its individual components across different DM strata (no DM, DM with or without insulin). Out of 951 patients, 20.0% had diabetes not on insulin and 2.5% had diabetes on insulin. The rate of the net composite endpoint was highest in patients receiving insulin (39.4 per 100 person-years vs 11.7 in diabetic patients not on insulin vs 14.0 in those without DM; p = 0.007). In DM, the higher risk of MACE was regardless of insulin use (p = 0.36). Conversely, the increase in bleeding complications was limited to patients on insulin (Hazard Ratio 2.31, 95% CI 0.93-5.71 vs no DM; p = 0.0105 across DM strata). On top of aspirin, the rates of the net composite endpoint were similar with ticagrelor/prasugrel or clopidogrel irrespective of DM status (p for interaction 0.63). In conclusion, in ACS patients, type 2 DM enhances the risk of MACE regardless of the DM cluster, whereas the propensity to bleeding related to DM seems confined to insulin-treated patients.

Background. The pandemic of severe acute respiratory syndrome COVID-19 drew the attention of researchers and practitioners worldwide to severe cardiovascular injury incurred by the new SARS-CoV-2 coronavirus. Objectives . A review and structuring of recent evidence on the pathophysiological mechanisms of SARS-CoV-2 impact on cardiovascular system and its major acute complications, assessment of indirect pandemic effects on treatment and diagnosis in practical cardiology. Methods . Literature sources were mined in the PubMed database with keywords “COVID-19” and “SARS-CoV-2” and the source type “Clinical Trial”, “Meta-Analysis”, “Review”, “Systematic Review”. The search depth was unrestricted, as the vast majority of publications appeared during the past year. Results . A screening of over 12,000 sources produced 329 most relevant articles available full-text, with 65 included in the review. A key factor of the SARS-CoV-2 penetration into human cell is protein S facilitating the virus—angiotensin-converting enzyme 2 binding and final fusion. Myocardial damage in COVID-19 can occur due to excessive inflammatory response, the disbalance of myocardial oxygen demand and supply, vasculitis, atherosclerotic plaque rupture, coronary spasm, hypoxic vascular damage and endothelial dysfunction, microthrombi formation. The most critical acute cardiovascular complications of COVID-19, apart from myocarditis, are cardiac arrhythmias, acute coronary syndromes, acute heart failure, thrombosis and embolism. The COVID-19 pandemic exerts an indirect negative influence on medical aid in patients with cardiovascular diseases and complications. Conclusion . Knowledge of the pathophysiological mechanisms of SARS-CoV-2 impact on cardiovascular system and major types of its acute complications allows targeted research into the scenarios of their prevention and treatment. A rational balance is expected between the infection control and treatment for critical noncommunicable, particularly, cardiovascular diseases.

Percutaneous coronary intervention (PCI) improves anginal chest pain in most, but not all, treated patients. PCI is associated with unplanned readmission for angina and non‐specific chest pain within 30‐days of index PCI. Patients with an index hospitalization for PCI between January–November in each of the years 2010–2014 were included from the United States Nationwide Readmissions Database. Of 2 723 455 included patients, the 30‐day unplanned readmission rate was 7.2% (n = 196 581, 42.3% female). This included 9.8% (n = 19 183) with angina and 11.1% (n = 21 714) with non‐specific chest pain. The unplanned readmission group were younger (62.2 vs 65.1 years; P

Summary Background The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS. Methods Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC). Findings The PRAISE score showed an AUC of 0·82 (95% CI 0·78–0·85) in the internal validation cohort and 0·92 (0·90–0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70–0·78) in the internal validation cohort and 0·81 (0·76–0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66–0·75) in the internal validation cohort and 0·86 (0·82–0·89) in the external validation cohort for 1-year major bleeding. Interpretation A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making. Funding None.

Background: The National Chest Pain Centers Program (NCPCP) is the largest nationwide, hospital-based, multifaceted, continuous quality improvement initiative, which aims to monitor and improve the quality of care for patients with acute chest pain. The accreditation of the standardized chest pain center is central to the project. The purpose of establishing chest pain centers is to develop a mechanism for “sending acute chest pain patients to a hospital with capabilities for the best treatment in the shortest time possible.” Objectives: This study aims to evaluate the effectiveness and implementation of the chest pain center accreditation and to identify factors that may influence its implementation in local settings. Study Design and Methods: Hospitals that have been accredited between January 2016 and September 2020 will be recruited in this study. We will conduct a self-controlled retrospective cohort study by comparing the care performance before, during, and after the accreditation. Measures for care performance will be selected based on the American College of Cardiology/American Heart Association clinical practice guidelines, which will be divided into prehospital processes, in-hospital processes, and in-hospital outcomes. For the implementation of the chest pain center accreditation, we will use a modified reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework to investigate the implementation process, and the consolidated framework for implementation research will be used to identify factors that emerge within the local context and influence the implementation fidelity and feasibility. Progress to Date: As of September 2020, there were 4,621 hospitals that registered the NCPCP, of which 1,507 hospitals were accredited. A total of 5,228,973 patients with a primary diagnosis on admission were enrolled from the registered hospitals, among which 34.6% were acute coronary syndromes. Conclusions: In this study, we proposed recommendations for improving the implementation of chest pain center accreditation, which will improve the quality of care for patients with acute chest pain and promote the sustainable development of chest pain center.

Aims: To evaluate risk factors for major adverse cardiac event (MACE) after the first acute coronary syndrome (ACS) and to examine the prevalence of risk factors in post-ACS patients. Methods: We used Finnish population-based myocardial infarction register, FINAMI, data from years 1993–2011 to identify survivors of first ACS (n = 12686), who were then followed up for recurrent events and all-cause mortality for three years. Finnish FINRISK risk factor surveys were used to determine the prevalence of risk factors (smoking, hyperlipidaemia, diabetes and blood pressure) in post-ACS patients (n = 199). Results: Of the first ACS survivors, 48.4% had MACE within three years of their primary event, 17.0% were fatal. Diabetes (p = 4.4 × 10−7), heart failure (HF) during the first ACS attack hospitalization (p = 6.8 × 10−15), higher Charlson index (p = 1.56 × 10−19) and older age (p = .026) were associated with elevated risk for MACE in the three-year follow-up, and revascularization (p = .0036) was associated with reduced risk. Risk factor analyses showed that 23% of ACS survivors continued smoking and cholesterol levels were still high (>5mmol/l) in 24% although 86% of the patients were taking lipid lowering medication. Conclusion: Diabetes, higher Charlson index and HF are the most important risk factors of MACE after the first ACS. Cardiovascular risk factor levels were still high among survivors of first ACS.

This review summarizes the published literature referring to the use and validity of the biomarker soluble urokinase plasminogen activator receptor (suPAR) when used for the assessment of patients with cardiac diseases. It is measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples. In cardiology a cut-off value range of 3.5 - 4.5 ng/mL has been commonly utilized. Different cut-off values may be applied based on the measuring kit used, the patient population and the clinical setting. A PubMed/Medline search was conducted aiming to identify all publications relevant to the use of suPAR in patients with cardiac diseases. A total of 39 studies were included in this review. suPAR as a marker of inflammation has been used more extensively in recent years, alone or in combination with other biomarkers of inflammation and cardiac pathology in the assessment of patients with acute and chronic cardiac diseases. suPAR is closely related to the pathophysiology of cardiac disease, and a number of publications encourages its use as a valuable biomarker in the assessment of patients presenting to the cardiology service. It may be most valuable in the risk assessment of patients with acute coronary syndromes and congestive heart failure, as suPAR elevation may be an independent predictor of mortality in these conditions. In conclusion, among several biomarkers used for clinical entities with underlying inflammatory pathophysiology including cardiac diseases, suPAR is a novel attractive index for the prognostic risk stratification of cardiac patients. More research is warranted to confirm its diagnostic and prognostic validity, alone or combined with other cardiac and inflammatory biomarkers.

AimsCeramide (Cer) and phosphatidylcholine (PC) lipids are associated with pathophysiological processes in cardiovascular (CV) diseases. A previously derived and validated plasma Cer-PC risk score (CERT2) was associated with CV death risk in patients with stable disease, but its prognostic value has not been evaluated in patients early post-acute coronary syndrome (ACS).Methods and resultsPrespecified plasma Cer and PC species in the CERT2 risk score were measured in 4871 subjects from SOLID-TIMI 52, which enrolled patients ≤30 days after ACS (median follow-up 2.5 years). The CERT2 score (scale 0–12 points) was calculated as previously defined. The primary outcome was CV death; Coronary heart disease death, all-cause death, hospitalization for heart failure (HF), myocardial infarction (MI) and stroke were also analyzed. Poisson models included baseline characteristics and established biomarkers. Patients with higher CERT2 risk scores were more likely to be older, female, current smokers, presenting with STEMI, and to have impaired renal function and higher LDL-C. After multivariable adjustment, patients in the highest risk score category remained at a nearly two-fold higher risk of CV death (adj relative risk [RR] 1.92, 95% CI 1.01–3.66, P = 0.047). Patients in the highest risk score category were also at higher risk of all-cause death (adj RR 2.01, 95% CI 1.21–3.35, P = 0.007), whereas the relationships with HF, MI, and stroke were attenuated with multivariable adjustment.ConclusionsA plasma ceramide and phospholipid-based risk score is associated with the risk of CV death independent of established clinical risk factors and biomarkers in patients after ACS.

Ventricular pacing may interfere with the interpretation of ECG among patients with suspected acute myocardial infarction (AMI), with possible delay of reperfusion therapy. Since left bundle branch block has a similar ECG morphology to right ventricular paced rhythm, Sgarbossa and modified Sgarbossa criteria could be useful in this setting. We present four clinical cases in which a recently proposed clinical-instrumental algorithm has been adopted to manage patients with right ventricular paced rhythm and suspected AMI.

Antithrombotic drugs, which include antiplatelets and anticoagulants, are effective in prevention and treatment of many cardiovascular disorders such as acute coronary syndromes, stroke, and venous thromboembolism and are among the drugs most commonly prescribed worldwide. The advent of direct oral anticoagulants, which are safer alternatives to vitamin K antagonists and do not require laboratory monitoring, has revolutionized the treatment of nonvalvular atrial fibrillation and venous thromboembolism. The combination of oral anticoagulant and antiplatelet therapy is required in many conditions of great clinical impact such as the coexistence of atrial fibrillation and coronary artery disease, with indication to percutaneous coronary intervention. However, strategies that combine anticoagulant and antiplatelet therapies lead to a significant increase in bleeding rates and it is crucial to find the right combination in the single patient in order to optimize the ischemic and bleeding risk. The aim of this review is to explore the evidence and controversies regarding the optimal combination of anticoagulant and antiplatelet therapy through the consideration of past dogmas and new perspectives from recent clinical trials and to propose a tailored therapeutic approach, according to specific clinical scenarios and individual patient characteristics. In particular, we separately explored the clinical settings of stable and acute coronary syndromes and percutaneous revascularization in patients with atrial fibrillation.

Background An increased risk of malignancy was reported with simvastatin/ezetimibe in 1,873 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial. Objectives The purpose of this study was to clarify this unexpected finding in a larger sample size of patients stabilized after acute coronary syndrome, we conducted a prospective systematic analysis of malignancy events in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Methods Within IMPROVE-IT, 17,708 patients post–acute coronary syndrome were randomized to either ezetimibe 10 mg or matching placebo on a background of simvastatin 40 mg who took ≥1 dose of the study drug. Suspected tumors (benign and malignant) reported by investigators or identified from a review of adverse events were adjudicated by oncologists without knowledge of drug assignment. The primary malignancy endpoint included new, relapsing, or progressive malignancies (excluding nonmelanotic skin malignancies). The secondary endpoint was death due to malignancy. Results In this trial, 1,470 patients developed the primary malignancy endpoint during a median 6 years of follow-up. The most common malignancy locations were prostate (18.9%), lung (16.8%), and bladder (8.8%) with no differences by treatment group (p > 0.05 for each location). Kaplan-Meier 7-year rates of malignancies were similar with ezetimibe and placebo (10.2% vs. 10.3%; hazard ratio: 1.03; 95% confidence interval: 0.93 to 1.14; p = 0.56), as were the rates for malignancy death (3.8% vs. 3.6%; hazard ratio: 1.04; 95% confidence interval: 0.88 to 1.23; p = 0.68). Conclusions Among 17,708 patients receiving simvastatin 40 mg daily, those randomized to ezetimibe 10 mg daily had a similar incidence of malignancy and deaths due to malignancy compared with those receiving placebo during a median follow-up of 6 years (96,377 patient-years). (IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin [Ezetimibe/Simvastatin] vs Simvastatin [P04103]; NCT00202878), Central Illustration

Aims Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor on top of aspirin is the cornerstone of therapy after acute coronary syndromes (ACS). Nonetheless, the safest and most efficacious P2Y12 for older patients who are both at high ischaemic and bleeding risk remains uncertain. We aimed to examine the effect of available P2Y12 inhibitors on ischaemic and bleeding endpoints in older adults with ACS. Methods and results Randomized clinical trials that reported separately the results of adults older >70 years for at least the primary endpoint [composite of death, myocardial infarction (MI), and stroke]. Seven studies (14 485 patients-years) were included. Network meta-analysis showed that prasugrel was associated with similar occurrence of the primary endpoint and of a secondary ischaemic endpoint (composite of MI and stroke) and was most likely the best treatment [Surface Under the Cumulative Ranking curve Analysis (SUCRA) 54.5 and 59.8, respectively]. With regards to major bleedings, clopidogrel showed the highest likelihood of event reduction (SUCRA 70.1%), while ticagrelor of stent thrombosis (SUCRA 55.6%). Our meta-regression with a fixed proportion of patients managed invasively of 100% confirmed these trends with increasing SUCRA. Conclusion Among older subjects with ACS, DAPT should be balanced upon ischaemic and bleeding risks as prasugrel is associated with the highest probability of reduction of ischaemic events and clopidogrel of bleedings. Ticagrelor had highest SUCRA for stent thrombosis reduction but seems suboptimal in older adults.

Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term ‘vulnerable plaque’ was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of ‘vulnerability’ of a specific lesion to the more comprehensive goal of identifying patient ‘cardiovascular vulnerability’. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and ‘local’ diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of ‘high-risk’ plaques occurring in ‘vulnerable’ patients.

Prompt identification of acute coronary syndrome is a challenge in clinical practice. The 12-lead electrocardiogram (ECG) is readily available during initial patient evaluation, but current rule-based interpretation approaches lack sufficient accuracy. Here we report machine learning-based methods for the prediction of underlying acute myocardial ischemia in patients with chest pain. Using 554 temporal-spatial features of the 12-lead ECG, we train and test multiple classifiers on two independent prospective patient cohorts (n = 1244). While maintaining higher negative predictive value, our final fusion model achieves 52% gain in sensitivity compared to commercial interpretation software and 37% gain in sensitivity compared to experienced clinicians. Such an ultra-early, ECG-based clinical decision support tool, when combined with the judgment of trained emergency personnel, would help to improve clinical outcomes and reduce unnecessary costs in patients with chest pain., Diagnosing a heart attack requires excessive testing and prolonged observation, which frequently requires hospital admission. Here the authors report a machine learning-based system based exclusively on ECG data that can help clinicians identify 37% more heart attacks during initial screening.

Background Platelet activation plays a crucial role in the pathogenesis of coronary artery disease (CAD). Platelet P-selectin (CD62P) is a classic platelet activation indicator on the platelet surface, and soluble TREM-like transcript-1 (sTLT-1) is a new indicator. However, the relationship between these two markers and CAD, especially in acute coronary syndrome (ACS), has not been elucidated. This study aimed to investigate CD62P expression on the platelet surface and sTLT-1 expression in serum, as well as to assess their relationship with CAD. Methods We measured the levels of CD62P and sTLT-1 in 83 patients with CAD compared to 49 controls. The association of these indicators with age, blood pressure, lipid profile, body mass index, and liver injury marker level were also examined. Results CD62P concentration was higher in CAD patients than in the control group (P P P Conclusions The consistency of sTLT-1 and CD62P expression levels in CAD patients indicates that sTLT-1 level, the same as CD62P, may be a new marker of platelet activation that is positively related to CAD.

Myocardial infarction (MI) still remains a leading cause of mortality throughout the world. An adverse cardiac remodeling, such as hypertrophy and fibrosis, in non-infarcted area leads to uncompensated heart failure with cardiac dysfunction. We previously demonstrated that canstatin, a C-terminus fragment of type IV collagen α2 chain, exerted anti-remodeling effect against isoproterenol-induced cardiac hypertrophy model rats. In the present study, we examined whether a long-term administration of recombinant canstatin exhibits a cardioprotective effect against the adverse cardiac remodeling in MI model rats. Left anterior descending artery of male Wistar rats was ligated and recombinant mouse canstatin (20 μg/kg/day) was intraperitoneally injected for 28 days. Long-term administration of canstatin improved survival rate and significantly inhibited left ventricular dilatation and dysfunction after MI. Canstatin significantly inhibited scar thinning in the infarcted area and significantly suppressed cardiac hypertrophy, nuclear translocation of nuclear factor of activated T-cells, interstitial fibrosis and increase of myofibroblasts in the non-infarcted area. Canstatin significantly inhibited transforming growth factor-β1-induced differentiation of rat cardiac fibroblasts into myofibroblasts. The present study for the first time demonstrated that long-term administration of recombinant canstatin exerts cardioprotective effects against adverse cardiac remodeling in MI model rats.

Objectives Diabetes mellitus (DM) and frailty are common in older patients with acute coronary syndromes (ACS). No data exists about its prognostic impact on long-term outcomes and their possible interaction in this setting. Design Observational prospective study. Setting Multicenter registry conducted in 44 hospitals in Spain. Participants Consecutive patients with ACS aged 80≥years. Measurements A comprehensive geriatric evaluation was performed during hospitalization, including frailty assessment by the FRAIL score. The impact of DM and frailty on the incidence of mortality/readmission at 24 months was analysed by a Cox regression model. Results A total of 498 patients were included (mean age 84.3 years). Prevalence of previous DM was 199/498 (40.0%). The rate of frail patients was 135/498 (27.1%). The incidence of mortality/readmission was higher frail patients (HR 2.49) (both p

Ischaemic heart disease (IHD), in particular acute coronary syndrome (ACS), comprising ST-elevation myocardial infarction, non-ST-elevation myocardial infarction and unstable angina, is the leading cause of death worldwide. Age is a major predictor of adverse outcome following ACS. COVID-19 infection seems to escalate the risk in older patients with heart disease. Increasing odds of in-hospital death is associated with older age following COVID-19 infection. Importantly, it seems older patients with comorbidities such as cardiovascular disease (CVD), in particular IHD, diabetes and hypertension, are at the highest risk of mortality following COVID-19 infection. The evidence is sparse on the optimal care of older patients with ACS with lack of robust randomised controlled trials. In this setting, with the serious threat imposed by the COVID-19 pandemic in the context of rapidly evolving knowledge with much unknown, it is important to weigh the risks and benefits of treatment strategies offered to older patients. In cases where risks outweigh the benefits, it might not be an unreasonable option to treat such patients with a conservative or a palliative approach. Further evidence to elucidate whether invasive management is beneficial in older patients with ACS is required out-with the COVID-19 pandemic. Though it is hoped that the actual acute phase of COVID-19 infection will be short lived, it is vital that important clinical research is continued, given the long-term benefits of ongoing clinical research for patients with long-term conditions, including CVD. This review aimed to evaluate the challenges and the management strategies in the care of older patients presenting with ACS in the context of the COVID-19 pandemic.

Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.

Cardiovascular diseases are among the main causes of morbimortality in the adult population. Among them, hypertension is a leading cause for stroke, heart disease and kidney failure. Also, as a result of arterial wall weakness, hypertension can lead to the development of dissecting aortic aneurysms, a rare but often fatal condition if not readily treated. In this work, we investigated the role of DBC1 in the regulation of vascular function in an ANGII-induced hypertension mouse model. We found that WT and DBC1 KO mice developed hypertension in response to ANGII infusion. However, DBC1 KO mice showed increased susceptibility to develop aortic dissections. The effect was accompanied by upregulation of vascular remodeling factors, including MMP9 and also VEGF. Consistent with this, we found decreased collagen deposition and elastic fiber fragmentation, suggesting that increased expression of MMPs in DBC1 KO mice weakens the arterial wall, promoting the formation of aortic dissections during treatment with ANGII. Finally, DBC1 KO mice had reduced cell proliferation in the intima-media layer in response to ANGII, paralleled with an impairment to increase wall thickness in response to hypertension. Furthermore, VSMC purified from DBC1 KO mice showed impaired capacity to leave quiescence, confirming the in vivo results. Altogether, our results show for the first time that DBC1 regulates vascular response and function during hypertension and protects against vascular injury. This work also brings novel insights into the molecular mechanisms of the development of aortic dissections.

Arterial thrombosis is a result of complex interaction between blood cells, soluble coagulation factors in plasma and vessel wall. Antiplatelet drugs do not always provide the necessary antithrombotic effect of sufficient strength, because their influence does not extend to all three factors involved in this process. Low doses of direct oral inhibitors of thrombin are able to potentiate antithrombotic effect of antiplatelet therapy. The combination of rivaroxaban in a dose of 2.5 mg and standard double antiplatelet therapy turned out to be the most promising for clinical use, since studies with dabigatran and apixaban at the II and III stages of the trials were found to be unsuccessful due to the unacceptably high frequency of bleeding. Studies of the combination of rivaroxaban at a dose of 2.5 mg and standard antiplatelet therapy conducted in previous years among patients with acute myocardial infarction showed a decrease in the frequency of complications of atherothrombosis associated with their ischemic nature, while at the same time there was a slight increase in hemorrhagic complications. In the COMPASS study the combination of rivaroxaban (2.5 mg) plus aspirin reduced the risk of the primary endpoint (myocardial infarction, ischemic stroke, cardiovascular death) more significantly than aspirin alone in patients with stable ischemic heart disease and ischemic brain disease. The pathophysiological rationales for the use of low doses of rivaroxaban when added to dual antiplatelet therapy are considered, and the significance of recent studies in patients with acute coronary syndrome, stable ischemic heart disease and in the prevention of ischemic stroke is discussed.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme family of phospholipase A2 produced by the inflammatory cell in atherosclerotic plaque. It is transported in the circulation, attached mainly to low-density lipoprotein-cholesterol (LDL-C). It hydrolyzes glycerophospholipids particularly fatty acids at the sn-2 position and produces numerous bioactive lipids; and leads to endothelial dysfunction, atherosclerotic plaque inflammation, and development of the necrotic core in plaques.:There are two kinds of phospholipase A2, namely: secretory phospholipase A2 (sPLA2) and Lp- PLA2. They are deemed as evolving predictors of cardiovascular disease (CVD) risk in hospitaland population-based studies, including healthy subjects, acute coronary syndromes (ACS) and patients with CVD. Unfortunately, Lp-PLA2 inhibitor (darapladib) and s-PLA2 inhibitor (varespladib methyl) failed to prove to lower the risk of composite CVD mortality, myocardial infarction and stroke in those with stable CVD and ACS.:Herein, we describe the explanation based on the existing data why there is still a discrepancy among them. So, it highlights the opinion that phospholipase A2 is merely the inflammatory biomarkers of CVD and playing an important role in atherosclerosis. Further, there is more spacious room to prove the causation.

Background Occlusion myocardial infarctions (OMIs) of the posterolateral walls are commonly missed by ST‐segment–elevation myocardial infarction (STEMI) criteria, with >50% of patients with circumflex occlusion not receiving emergent reperfusion and experiencing increased mortality. ST‐segment depression maximal in leads V1–V4 (STDmaxV1–4) has been suggested as an indicator of posterior OMI. Methods and Results We retrospectively reviewed a high‐risk population with acute coronary syndrome. OMI was defined from prior studies as a culprit lesion with TIMI (Thrombolysis in Myocardial Infarction) 0 to 2 flow or TIMI 3 flow plus peak troponin T >1.0 ng/mL or troponin I >10 ng/mL. STEMI was defined by the Fourth Universal Definition of Myocardial Infarction. ECGs were interpreted blinded to outcomes. Among 808 patients, there were 265 OMIs, 108 (41%) meeting STEMI criteria. A total of 118 (15%) patients had “suspected ischemic” STDmaxV1–4, of whom 106 (90%) had an acute culprit lesion, 99 (84%) had OMI, and 95 (81%) underwent percutaneous coronary intervention. Suspected ischemic STDmaxV1–4 had 97% specificity and 37% sensitivity for OMI. Of the 99 OMIs detected by STDmaxV1–4, 34% had P =0.028). Conclusions Among patients with high‐risk acute coronary syndrome, the specificity of ischemic STDmaxV1–4 was 97% for OMI and 96% for OMI requiring emergent percutaneous coronary intervention. STEMI criteria missed half of OMIs detected by STDmaxV1–4. Ischemic STDmaxV1–V4 in acute coronary syndrome should be considered OMI until proven otherwise.

Fulminant myocarditis (FM) is a severe disease with a rapidly progressive and life-threatening course caused mainly by viral infection. The symptoms, laboratory findings, and presence of ECG changes resemble acute coronary syndrome. Therefore, coronary angiography is usually helpful in making the appropriate diagnosis. However, failure to obtain complete coronary artery images due to coronary artery anatomic variations poses a challenge for the diagnosis of FM. Here, we report a case of FM preliminarily diagnosed as acute coronary syndrome (ACS) due to the presence of coronary artery anomaly.

Background Discrepant data were reported about hospital admissions for ST-segment elevation myocardial infarction (STEMI) during COVID-19 pandemic. We reviewed studies reporting STEMI hospitalizations during COVID-19 pandemic, investigating whether differences in COVID-19 epidemiology or public health-related factors could explain discrepant findings in different countries. Methods Search through MedLine, Embase, Scopus, Web-of-Science, Cochrane Register of Controlled Trials, of studies comparing STEMI admissions during COVID-19 pandemic with a reference period, without language restrictions, as registered in PROSPERO International Prospective Register of Systematic Reviews. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed. Data independently extracted by multiple investigators were pooled using a random-effects model. Health-related metrics were from publicly-available sources. Results We included 79 articles (111,557 STEMI cases, from 57 countries). During peak COVID-19 pandemic, overall incidence rate-ratio (IRR) of STEMI hospitalizations over reference period decreased (0.80; 95% CI 0.76–0.84; p

The evaluation of monocyte subset distribution among acute coronary syndrome (ACS) patients according to culprit coronary plaque morphology has never been explored. We evaluated whether there were significant differences in frequency of circulating monocyte subsets isolated from ACS patients according to optical coherence tomography (OCT) investigation of plaque erosion and rupture. We enrolled 74 patients with non-ST-elevation ACS (NSTE-ACS), 21 of them underwent OCT investigation of the culprit coronary plaque and local macrophage infiltration (MØI) assessment. As control, we enrolled 30 chronic coronary syndrome (CCS) patients. We assessed the frequency of monocyte subsets in the whole study population, in reliance on their CD14 and CD16 expression (classical, CM: CD14++CD16–; intermediates, IM: CD14++CD16+; non-classical, NCM: CD14+CD16++). Then, we tested the effect of lipopolysaccharide (LPS) (a CD14 ligand) on peripheral blood mononuclear cells (PBMCs) of NSTE-ACS patients, quantifying the inflammatory cytokine levels in cell-culture supernatants. Our data proved that monocyte subsets isolated from NSTE-ACS patients represent a peculiar biological signature of the pathophysiological mechanism lying beneath atherosclerotic plaque with a ruptured fibrous cap (RFC) as compared with plaque erosion. Moreover, the magnitude of LPS-mediated effects on IL-1β, IL-6, and IL-10 cytokine release in cell-culture supernatants appeared to be greater in NSTE-ACS patients with RFC. Finally, we described a fourth monocyte population never explored before in this clinical setting (pre-classical monocytes, PCM: CD14+CD16–) that was prevalent in NSTE-ACS patients as compared with CCS and, especially, in patients with RFC and culprit plaque with MØI.

Background All of Us is a novel research program that aims to accelerate research in populations traditionally underrepresented in biomedical research. Our objective was to evaluate the burden of cardiovascular disease (CVD) in broadly defined underrepresented groups. Methods and Results We evaluated the latest data release of All of Us. We conducted a cross‐sectional analysis combining survey and electronic health record data to estimate the prevalence of CVD upon enrollment in underrepresented groups defined by race, ethnicity, age (>75 years), disability (not able to carry out everyday physical activities), sexual orientation and gender identity lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA+), income (annual household income 75 years (OR, 1.90; 95% CI, 1.81–1.99), disability (OR, 1.60; 95% CI, 1.53–1.68), and income Conclusions Among participants enrolled in All of Us, underrepresented groups defined based on race, ethnicity and other factors have a disproportionately high burden of CVD. The All of Us research program constitutes a powerful platform to accelerate research focused on individuals in underrepresented groups.

BACKGROUND: Inflammation plays a pivotal role in coronary artery disease (CAD). The anti- inflammatory drug colchicine seems to reduce ischemic events in patients with CAD. So far there is equipoise about its safety and impact on mortality METHODS AND RESULTS: To evaluate the utility of colchicine in patients with acute and chronic CAD, we performed a systematic review and meta- analysis. MEDLINE, EMBASE, Cochrane CENTRAL and conference abstracts were searched from January 1975 to October 2020. Randomized trials assessing colchicine compared with placebo/standard therapy in patients with CAD were included. Data were combined using random- effects models. The reliability of the available data was tested using trial sequential analyses. Of 3108 citations, 13 randomized trials (n=13 125) were included. Colchicine versus placebo/standard therapy in patients withCAD reduced risk of myocardial infarction (odds ratio [OR] 0.64; 95% CI, 0.46 ��� 0.90; P= 0.01; I 41%) and stroke/transient ischemic attack (OR 0.50; 95% CI, 0.31��� 0.81; P=0.005; I 0%). But treatment with colchicine compared with placebo/standard therapy had no influence on all- cause and cardiovascular mortality (OR 0.96; 95% CI, 0.65��� 1.41; P=0.83; I 24%; and OR 0.82; 95% CI, 0.55��� 1.22; P=0.45; I 0%, respectively). Colchicine increased the risk for gastrointestinal side effects (P, + ID der Publikation: unilu_54969 + Sprache: Englisch + Letzte Aktualisierung: 2021-10-27 16:06:46

Background Rigorous incidence data for acute myocardial infarction (AMI) in sub‐Saharan Africa are lacking. Consequently, modeling studies based on limited data have suggested that the burden of AMI and AMI‐associated mortality in sub‐Saharan Africa is lower than in other world regions. Methods and Results We estimated the incidence of AMI in northern Tanzania in 2019 by integrating data from a prospective surveillance study (681 participants) and a community survey of healthcare‐seeking behavior (718 participants). In the surveillance study, adults presenting to an emergency department with chest pain or shortness of breath were screened for AMI with ECG and troponin testing. AMI was defined by the Fourth Universal Definition of AMI criteria. Mortality was assessed 30 days following enrollment via in‐person or telephone interviews. In the cluster‐based community survey, adults in northern Tanzania were asked where they would present for chest pain or shortness of breath. Multipliers were applied to account for AMI cases that would have been missed by our surveillance methods. The estimated annual incidence of AMI was 172 (207 among men and 139 among women) cases per 100 000 people. The age‐standardized annual incidence was 211 (263 among men and 170 among women) per 100 000 people. The estimated annual incidence of AMI‐associated mortality was 87 deaths per 100 000 people, and the age‐standardized annual incidence was 102 deaths per 100 000 people. Conclusions The incidence of AMI and AMI‐associated mortality in northern Tanzania is much higher than previously estimated and similar to that observed in high‐income countries.

Background Although patients with a cancer history have a 2 to 3 times higher risk for acute coronary syndrome (ACS), the morphological characteristics of ACS culprit plaque in those patients and their relations with clinical outcomes remain unknown. Methods and Results This retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent optical coherence tomography‐guided emergent percutaneous coronary intervention. Patients were categorized into those without a cancer history, those with a cancer history, and those currently receiving cancer treatment. ACS culprit lesions were classified as plaque rupture, plaque erosion, or calcified nodule using optical coherence tomography. Plaque erosion frequency was significantly higher in culprit lesions of patients with current cancer and patients with cancer history than in those of patients without cancer history (56.3% versus 61.7% versus 36.5%). Calcified nodule incidence was significantly higher in patients without cancer history than in patients with current cancer and patients without cancer history (patients with current cancer: 12.4% versus patients without cancer history: 25.5% versus patients without cancer history: 12.6%, P P P =0.002). Nonplaque rupture in ACS culprit lesions was independently associated with major adverse cardiovascular events (HR, 1.60; P =0.011). Conclusions Patients with a cancer history had significantly worse clinical outcomes after ACS than those without a cancer history. Those with a cancer history had significantly higher plaque erosion and calcified nodule incidences in the ACS culprit lesions, which might partly explain their worse clinical outcomes. Registration URL: www.umin.ac.jp/ctr/index.htm . Unique Identifier: UMIN000038442.

The main causes of death in patients with chronic kidney disease (CKD) are of cardiovascular nature. The interaction between traditional cardiovascular risk factors (CVRF) and non-traditional risk factors (RF) triggers various complex pathophysiological mechanisms that will lead to accelerated atherosclerosis in the context of decreased renal function. In terms of mortality, CKD should be considered equivalent to ischemic coronary artery disease (CAD) and properly monitored. Vascular calcification, endothelial dysfunction, oxidative stress, anemia, and inflammatory syndrome represents the main uremic RF triggered by accumulation of the uremic toxins in CKD subjects. Proteinuria that appears due to kidney function decline may initiate an inflammatory status and alteration of the coagulation—fibrinolysis systems, favorizing acute coronary syndromes (ACS) occurrence. All these factors represent potential targets for future therapy that may improve CKD patient’s survival and prevention of CV events. Once installed, the CAD in CKD population is associated with negative outcome and increased mortality rate, that is the reason why discovering the complex pathophysiological connections between the two conditions and a proper control of the uremic RF are crucial and may represent the solutions for influencing the prognostic. Exclusion of CKD subjects from the important trials dealing with ACS and improper use of the therapeutical options because of the declined kidney functioned are issues that need to be surpassed. New ongoing trials with CKD subjects and platelets reactivity studies offers new perspectives for a better clinical approach and the expected results will clarify many aspects.

Aims To compare the safety and efficacy of edoxaban combined with P2Y12 inhibition following percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) presenting with an acute coronary syndrome (ACS) or chronic coronary syndrome (CCS). Methods and results In this pre-specified sub-analysis of the ENTRUST-AF PCI trial, participants were randomly assigned 1:1 to edoxaban- or vitamin K antagonist (VKA)-based strategy and randomization was stratified by ACS (edoxaban n = 388, VKA n = 389) vs. CCS (edoxaban n = 363, VKA = 366). Participants received edoxaban 60 mg once-daily plus a P2Y12 inhibitor for 12 months, or VKA combined with a P2Y12 inhibitor and aspirin 100 mg (for 1–12 months). The primary bleeding endpoint at 12 months occurred in 59 (15.2%) vs. 79 (20.3%) ACS patients [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.59–1.02, P = 0.063], and in 69 (19.0%) vs. 73 (19.9%) CCS patients (HR: 0.94, 95%CI: 0.68–1.31, P = 0.708) with edoxaban- and VKA-based therapy, respectively [P for interaction (P-int) = 0.2741]. The main secondary endpoint (composite of CV death, myocardial infarction, stroke, systemic embolic events, or definite stent thrombosis) in ACS patients was 33 (8.5%) vs. 28 (7.2%) (HR: 1.16, 95%CI: 0.70–1.92), compared with 16 (4.4%) vs. 18 (4.9%) (HR: 0.91, 95%CI: 0.47–1.78) CCS patients with edoxaban and VKA-based therapy, respectively (P-int = 0.5573). Conclusions In patients with AF who underwent PCI, the edoxaban-based regimen, as compared with VKA-based regimen, provides consistent safety and similar efficacy for ischaemic events in patients with AF regardless of their clinical presentation.

During the pandemic of coronavirus disease (COVID 19), anecdotal reports have been emerging all over the world that cases of acute cardiovascular emergencies such as ST-elevation myocardial infarction (MI) have decreased to the extent of 30%–70% at various hospitals. The number of primary percutaneous interventions has significantly decreased all over the world including developed nations. We present case reports of acute coronary syndromes (ACS) who presented to our hospital after the period of lockdown during the COVID-19 pandemic. These patients presented late to the hospital when we compare the ACS presentation before the lockdown period. Because of the late presentation, these patients developed heart failure and other complications leading to their death.

Aims To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury. Methods and results One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case–control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P < 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P < 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P 4 were associated with larger infarcts [>10% left ventricular (LV) mass]. Conclusion The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts.

Macrophage migration inhibitory factor (MIF) has been recognized as a major player in the pathogenesis of atherosclerosis. This study determined the association between polymorphisms of MIF gene and acute coronary syndrome (ACS). The polymorphism of MIF gene (rs755622, rs1007888 and rs2096525) was analyzed in 1153 healthy controls and 699 ACS cases in Chinese Han population. Plasma MIF level was also measured in part of ACS patients (139/19.9%) and healthy controls (129/11.2%) randomly. Most participants including healthy controls and ACS patients carried rs755622 GG (63.1% vs. 56.7%) and CG genotypes (33.1% vs. 38.9%) and G allele of rs755622 (79.6% vs. 76.1%, respectively), while CC genotype (3.8% vs. 4.4%) and C allele (20.4% vs. 23.9%) carriers were the lowest. Multivariate logistic regression analysis showed that carriers with rs755622 C allele had a higher risk of ACS compared to other genotypes (AOR = 1.278, 95% CI: 1.042–1.567). In addition, CC genotype carriers had the highest plasma levels of MIF than other genotype carriers. The MIF level in ACS patients with CC genotype was significantly higher than ACS patients carrying GG genotype and healthy controls carrying 3 different genotypes of MIF gene rs755622. Our findings indicate that MIF gene rs755622 variant C allele is associated with increased risk of ACS. Identification of this MIF gene polymorphism may help for predicting the risk of ACS.

Ivabradine is a heart rate-lowering agent that inhibits pacemaker funny current (If). It has been approved by the European Medicines Agency and the US Food and Drug Administration for patients with stable angina and heart failure (HF). AF is a common issue especially in ischaemic heart disease and HF patients. In contrast to experimental findings and a limited number of clinical trials that demonstrate the emerging role of ivabradine for heart rate control in AF or maintenance of sinus rhythm, there is accumulating contradictory data indicating that there is, in fact, an increased incidence of new-onset AF among people who are taking ivabradine in clinical practice. This article reviews the most recent evidence highlighting the diversity of data in relation to the use of ivabradine and the onset of AF and whether it has a legitimate role in AF treatment and the maintenance of sinus rhythm.

Ischemic heart disease is one of the most prevalent diseases with a high impact on mortality and morbidity. The main process implicated in acute coronary syndromes (ACS) including its most severe form, the ST elevation myocardial infarction (STEMI), is the development of thrombosis subsequently of plaque erodation or rupture. The thrombus is formed by aggregates of platelets that furthermore drive the process of coagulation, that in this turn stimulates platelet aderation and aggregation, causing a vicious circle. From these physiopathological mechanims derive the indication and role of antiplatelets and anticoagulation in STEMI. Antiplatelets and anticoagulants play a central role in the therapeutic management of STEMI along with the interventional therapy. Correctly conducted by all physicians involved in the management of patients with STEMI, it reduces the area of ischemia, as well as mortality and other major adverse cardiovascular events. The following article will review the antithrombotic treatment adjuvant to the interventional treatment and the evidence based indications for treatment in STEMI.

Acute coronary syndromes (ACS) are one of the main causes of morbidity and mortality in the world. It affects people in the middle and late-life, but the biggest psycho-social and financial impact is among the active young population. After the acute event they have to return to work and to their families for which they represent the principal support. Besides medication and prompt revascularization therapies, cardiac rehabilitation (CR) has an important role in regaining most of the initial physical and psychological state. Despite the proved benefit of the CR, referral and participation rate is very low, suggesting that there is more to do in this old but very underappreciated field. Key words: acute coronary syndromes, myocardial infarction, young, cardiac rehabilitation, secondary prevention

BACKGROUND: The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection. We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).METHODS AND RESULTS: In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p CONCLUSION: While the effect of IPC is reduced during hyperglycemia in rats without T2DM, endogenous cardioprotection in animals with T2DM is not influenced by hyperglycemia and the capacity for exogenous cardioprotection by IPC is preserved. MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.

Background Timely emergency medical services (EMS) response, management, and transport of patients with suspected acute coronary syndrome (ACS) significantly reduce delays to emergency treatment and improve outcomes. We evaluated EMS response, scene, and transport times and adherence to proposed time benchmarks for patients with suspected ACS in North Carolina from 2011 to 2017. Methods and Results We conducted a population‐based, retrospective study with the North Carolina Prehospital Medical Information System, a statewide electronic database of all EMS patient care reports. We analyzed 2011 to 2017 data on patient demographics, incident characteristics, EMS care, and county population density for EMS‐suspected patients with ACS, defined as a complaint of chest pain or suspected cardiac event and documentation of myocardial ischemia on prehospital ECG or prehospital activation of the cardiac care team. Descriptive statistics for each EMS time interval were computed. Multivariable logistic regression was used to quantify relationships between meeting response and scene time benchmarks (11 and 15 minutes, respectively) and prespecified covariates. Among 4667 patients meeting eligibility criteria, median response time (8 minutes) was shorter than median scene (16 minutes) and transport (17 minutes) time. While scene times were comparable by population density, patients in rural (versus urban) counties experienced longer response and transport times. Overall, 62% of EMS encounters met the 11‐minute response time benchmark and 49% met the 15‐minute scene time benchmark. In adjusted regression analyses, EMS encounters of older and female patients and obtaining a 12‐lead ECG and venous access were independently associated with lower adherence to the scene time benchmark. Conclusions Our statewide study identified urban–rural differences in response and transport times for suspected ACS as well as patient demographic and EMS care characteristics related to lower adherence to scene time benchmark. Strategies to reduce EMS scene times among patients with ACS need to be developed and evaluated.

Introduction: Takotsubo syndrome is a complex entity that, although it usually has a good prognosis, can be life threatening. While recent advances have improved the knowledge of takotsubo syndrome, many aspects of its etiology still remain uncertain. Metabolomics, a hypothesis generating approach, could provide novel pathophysiology information about this disease. Methods and Results: Serum samples were obtained from takotsubo (n = 19) and acute myocardial infarction patients (n = 8) at the cath lab and, in the case of takotsubo, again once the patient had recovered, 3 months after the main event. 1H NMR spectra of the serum were acquired at 9.4T using a CPMG pulse sequence (32 ms effective delay). Supervised and unsupervised pattern recognition approaches where applied to the data. Pattern recognition was able to differentiate between takotsubo and acute myocardial infarction during the acute phase with 95% accuracy. Myocardial infarction patients showed an increase in lipid signals, a known risk factor for the disease while takotsubo patients showed a relative increase in acetate that could suggest a reduced turnover of the Krebs cycle. When comparing acute and recovered phases, we could detect an increase in alanine and creatine once patients recovered. Conclusions: Our results demonstrate that takotsubo syndrome is metabolically different than AMI, showing limited myocardial energy production capacity during the acute phase. We achieved high classification success against AMI, however, this study should be considered as a proof of concept regarding clinical application of metabolic profiling in takotsubo cardiomyopathy.