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The resorbable magnesium scaffold (RMS) is a second-generation bioresorbable scaffold (BRS) that has shown conflicting results in previous studies. These findings suggest that patient selection and implantation technique may have an impact on clinical outcomes. This study aimed to investigate the safety and long-term effectiveness of RMS in a narrowly selected population. SHERPA-MAGIC is an investigator-driven, multicenter, prospective, single-arm study that enrolled patients undergoing BRS coronary implantation in 18 Italian centers. The present analysis considered the first 543 enrolled patients treated with RMS, with a minimum follow-up of 1 year. The study protocol included strict criteria for patient selection and standardization of RMS implantation. The primary outcome was the occurrence of the vessel-oriented composite endpoints (VOCE), including cardiac death, target vessel myocardial infarction, and ischemia-driven target vessel revascularization. Overall, 635 vessels were treated. The 1-year cumulative occurrence of VOCE was 22 (3.5%, 95% CI 2.2%–5.2%), which was significantly lower than the prespecified estimation (from 5.5% to 8.5%). At the median follow-up of 3.5 [2.6–4.3] years, there were 3 (0.5%) cardiac deaths, 12 (1.9%) target vessel myocardial infarctions, and 33 (5.2%) ischemia-driven target vessel revascularizations. A total of 37 (5.8%, 95%CI 4.1%–7.9%) VOCEs were detected. Scaffold thrombosis occurred in 4 (0.6%, 95%CI 0.1%–1.6%) cases. Patient-level analysis confirmed the findings of the vessel-level analysis. These results confirm the safety and performance of RMS technology. If confirmed in randomized controlled trials, they may rekindle interest in the use of scaffolds in daily practice. Central illustration summarizing the qualifying criteria for patient and lesion selection and the standardized RMS implantation technique according to SHERPA-MAGIC protocol. In the bottom panel, the main results of the study are listed: the cumulative occurrence of VOCE at 1 year follow-up and at median follow-up; the cumulative occurrence of POCE at median follow-up; the rate of instent restenosis and Scaffold Thrombosis. [Display omitted] • Resorbable magnesium scaffold (RMS) is a second-generation bioresorbable scaffold (BRS) showing conflicting results in first studies. • The long-term clinical outcome of the first 543 patients enrolled in the SHERPA-MAGIC study expands the recent BIOSOLVE-IV findings. • Indeed, the present results confirm the safety and the good performance of the RMS technology in the treatment of mid-to-large size coronary vessels in a real-world population. • The combination of adequate patient selection and meticulous implantation technique guaranteed to maximize the safety and efficacy of RMS. [ABSTRACT FROM AUTHOR]

Aspirin is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents. This study compared P2Y 12 inhibitor monotherapy vs aspirin in patients with CAD. We conducted a patient-level meta-analysis of randomized trials comparing P2Y 12 inhibitor monotherapy vs aspirin monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis. Patient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y 12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive aspirin. Risk of the primary outcome was lower with P2Y 12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P = 0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P < 0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P = 0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P = 0.020) with P2Y 12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y 12 inhibitors. Given its superior efficacy and similar overall safety, P2Y 12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in patients with established CAD. (P2Y 12 Inhibitor or Aspirin Monotherapy as Secondary Prevention in Patients With Coronary Artery Disease: An Individual Patient Data Meta-Analysis of Randomized Trials [PANTHER collaborative initiative]; CRD42021290774) [Display omitted] [ABSTRACT FROM AUTHOR]

The term "single-sample rule-out" refers to the ability of very low concentrations of high-sensitivity cardiac troponin (hs-cTn) on presentation to exclude acute myocardial infarction with high clinical sensitivity and negative predictive value. Observational and randomized studies have confirmed this ability. Some guidelines endorse use of a concentration of hs-cTn at the assay's limit of detection, while other studies have validated the use of higher concentrations, allowing this approach to identify a greater proportion of patients at low risk. In most studies, at least 30% of patients can be triaged with this approach. The concentration of hs-cTn varies according to the assay used and sometimes how regulations permit reporting. It is clear that patients need to be at least 2 hours from the onset of symptoms being evaluated. Caution is warranted, particularly with older patients, women, and patients with underlying cardiac comorbidities. [Display omitted] • Rapid, safe, and accurate exclusion of acute myocardial infarction can facilitate triage of patients in the emergency department. • Observational and randomized studies have found that a single low assay-dependent, hs-cTn measurement taken >2 hours after symptom onset in a patient with a nonischemic electrocardiogram can effectively exclude acute MI. • Additional studies are needed to assess the utility of this approach in patients undergoing evaluation earlier after the onset of symptoms and to establish optimum blood level thresholds for women and patients with specific comorbidities. [ABSTRACT FROM AUTHOR]

Heart failure is an important cause of morbidity and mortality. More than 20 years ago, special interest was drawn to cell therapy as a means of restoring damaged hearts to working condition. But progress has not been straightforward as many of our initial assumptions turned out to be wrong. In this review, we critically examine the last 20 years of progress in cardiac cell therapy and focus on several of the popular beliefs surrounding cell therapy to illustrate the mechanisms involved in restoring heart function after cardiac injury. Are they true or false? [ABSTRACT FROM AUTHOR]

Ischaemic heart disease is the primary cause of death worldwide with myocardial infarction (MI) contributing to significant morbidity and mortality. The human heart has a limited capacity to regenerate and the significant loss of cardiomyocytes after MI can overwhelm this limited innate regenerative capability. This is in part compensated for by the creation of collagen-rich scar tissue. Therapeutic angiogenesis is an exciting prospect that can assist cardiac regeneration after MI with various approaches having been explored. This review will focus on results from clinical growth factor trials, and the lack of clinical translation. Inconsistencies in results from these may be due to heterogeneity within patient selection and an incomplete understanding of therapeutic differences between isoforms of active agents. The technology used has also evolved with recombinant protein and, subsequently, gene therapy being utilised. Innovative therapeutic designs, such as combinatorial therapies, might help to resolve these issues in the future. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide and the primary underlying risk factor for heart failure. Despite decades of research and clinical trials, there are no drugs currently available to prevent organ damage from acute ischaemic injuries of the heart. In order to address the increasing global burden of heart failure, drug, gene, and cell-based regeneration technologies are advancing into clinical testing. In this review we highlight the burden of disease associated with AMI and the therapeutic landscape based on market analyses. New studies revealing the role of acid-sensitive cardiac ion channels and other proton-gated ion channels in cardiac ischaemia are providing renewed interest in pre- and post-conditioning agents with novel mechanisms of action that may also have implications for gene- and cell-based therapeutics. Furthermore, we present guidelines that couple new cell technologies and data resources with traditional animal modelling pipelines to help de-risk drug candidates aimed at treating AMI. We propose that improved preclinical pipelines and increased investment in drug target identification for AMI is critical to stem the increasing global health burden of heart failure. [ABSTRACT FROM AUTHOR]

The association between thyroid stimulating hormone (TSH) and cardiovascular disease has mainly been determined using clinical categories of disease. We tested the hypothesis that TSH on a continuous scale is associated with risk of atrial fibrillation (AF), myocardial infarction (MI), stroke, heart failure (HF), aortic valve stenosis (AVS), and major adverse cardiovascular events (MACE) and whether these associations are likely to be causal. We first tested whether plasma TSH on a continuous scale was observationally associated with incident cardiovascular events in a prospective cohort study of 105,224 individuals from the Copenhagen General Population Study followed for a median 7 years. Next, we tested whether a genetic risk score weighted on TSH was associated with cardiovascular endpoints. Finally, using Mendelian randomization, we tested whether the observed associations were likely to be causal. Using restricted cubic splines, lower concentrations of TSH relative to the population median (=1.53 mIU/L) were associated with higher risk of AF, MI, stroke, HF, AVS, and MACE. Comparing individuals with TSH ≤5th percentile (≤0.54 mIU/L) versus >50th percentile (>1.53 mIU/L), hazard ratios (HRs) ranged from 1.12 (1.00–1.26) for stroke to 1.27 (1.11–1.46) for HF. Genetic risk estimates per standard deviation decrease in TSH were 1.28 (1.08–1.52) for AF, 1.35 (1.06–1.71) for MI, 1.06 (0.89–1.26) for stroke, 1.19 (0.94–1.52) for HF, 1.53 (1.03–2.26) for AVS, and 1.09 (0.97–1.23) for MACE. In 105,224 individuals from the general population low plasma TSH was observationally and genetically associated with increased risk of AF, MI, and AVS suggesting that these observations may reflect causal pathways. [Display omitted] • We tested the hypothesis that TSH was associated with cardiovascular disease (CVD). • 105,224 individuals from the general population were followed for a median of 7 years. • Observationally, TSH below the median was associated with increased risk of CVD. • Genetically, Mendelian randomization suggested possible causal associations. [ABSTRACT FROM AUTHOR]

Mendelian randomization confirmed multiple risk factors for primary events of coronary artery disease (CAD), but no such studies have been performed on recurrent major coronary events despite interesting insights derived from other designs. We examined the associations between genetically-influenced classical cardiovascular risk factors and the risk of recurrent major coronary events in a cohort of CAD patients. We included all first-time CAD cases (defined as angina pectoris, chronic ischemic heart disease or acute myocardial infarction) of European ancestry from the UK Biobank. Cases were followed till the end of follow-up, death or when they developed a recurrent major coronary event (chronic ischemic heart disease or acute myocardial infarction). Standardized weighted genetic risk scores were calculated for body mass index (BMI), systolic blood pressure, LDL cholesterol and triglycerides. From a total of 22,949 CAD patients (mean age at first diagnosis 59.8 (SD 7.3) years, 71.1% men), 12,539 (54.6%) reported a recurrent major coronary event within a period of maximum 17.8 years. One standard deviation higher genetically-determined LDL cholesterol was associated with a higher risk of a recurrent major coronary event (odds ratio: 1.08 [95% confidence interval: 1.05, 1.11]). No associations were observed for genetically-influenced BMI (1.00 [0.98, 1.03]), systolic blood pressure (1.01 [0.98, 1.03]) and triglycerides (1.02 [0.995, 1.05]). Despite the use risk-reducing medications following a first coronary event, this study provided genetic evidence that, of the classical risk factors, mainly high LDL cholesterol was associated with a higher risk of developing recurrent major coronary events. [Display omitted] • Most Mendelian randomization studies were performed on primary disease. • In atherosclerosis patients, LDL cholesterol associated with secondary disease. • Other classical cardiovascular disease did not associate with secondary disease. • LDL cholesterol should be mainly targeted to reduce secondary disease risk. [ABSTRACT FROM AUTHOR]

• 4S-AF scheme score is distributed normally in post-MI NOAF. • High 4S-AF scheme score is associated poor survival in patients with post-MI NOAF. • 4S-AF scheme score improves the prognostic predictive performance of GRACE score in post-MI NOAF. The 4S-AF scheme (Stroke risk [St], Symptom severity [Sy], Severity of atrial fibrillation burden [Sb], Substrate [Su]) is a novel approach for the holistic characterization of AF. We aimed to investigate the prognostic implications of the 4S-AF scheme score in acute myocardial infarction (AMI) patients with new-onset atrial fibrillation (NOAF). We included 262 patients with post-MI NOAF who had complete data for the 4S-AF scheme evaluation between February 2014 and March 2018. The 4S-AF scheme score was calculated as a sum of each domain with a maximum of 9. The primary outcome was all-cause death. Of 262 patients (66.0% males, mean age 74.5 ± 10.4 years) were analyzed. The mean 4S-AF scheme score was 5.0 ± 1.6. There were 62 (27.3%) all-cause deaths within a median follow-up of 2.6 years. According to multivariable Cox regression models, each 1-point increase in the 4S-AF scheme score was significantly associated with 39% increased all-cause mortality (HR: 1.39, 95% CI: 1.16–1.67, P <0.001), which was mainly driven by the Sb (HR: 1.43, 95%CI: 1.05–1.95, P = 0.025) and Su (HR: 1.53, 95%CI: 1.17–2.02, P = 0.002) domains. Adding the 4S-AF scheme score on top of the Global Registry of Acute Coronary Events score could significantly improve its discriminative capability (C-index from 0.713 to 0.761, P = 0.039) and reclassification performance (continuous net reclassification improvement: 41.0% [95%CI: 12.5–69.6]; integrated discrimination improvement: 5.1% [95%CI: 2.2–8.1]) for all-cause mortality. Characterization of NOAF using the 4S-AF scheme aids in the risk stratification of AMI patients with NOAF. [Display omitted] [ABSTRACT FROM AUTHOR]

ST-elevation myocardial infarction (STEMI) is typically caused by thrombotic occlusion of a coronary artery with subsequent hypoperfusion and myocardial necrosis. In approximately half of patients with STEMI, despite successful restoration of epicardial coronary patency, downstream myocardium perfusion remains impeded. Coronary microvascular injury is one of the key mechanisms behind suboptimal myocardial perfusion and it is primarily, yet not exclusively, related to distal embolization of atherothrombotic material following recanalization of the culprit artery. Routine manual thrombus-aspiration has failed to show clinical efficacy in this scenario. This could be related with limitations in technology adopted as well as patients' selection. To this end, we set out to explore the efficacy and safety of stent retriever-assisted thrombectomy based on clot-removal device routinely used in stroke intervention. The stent RETRIEVEr thrombectomy for thrombus burden reduction in patients with Acute Myocardial Infarction (RETRIEVE-AMI) study has been designed to establish whether stent retriever-based thrombectomy is safe and more efficacious in thrombus modification than the current standard of care: manual thrombus aspiration or stenting. The RETRIEVE-AMI trial will enrol 81 participants admitted for primary PCI for inferior STEMI. Participants will be 1:1:1 randomised to receive either standalone PCI, thrombus aspiration and PCI, or retriever-based thrombectomy and PCI. Change in thrombus burden will be assessed via optical coherence tomography imaging. A telephone follow-up at 6 months will be arranged. It is anticipated by the investigators that stent retriever thrombectomy will more effectively reduce the thrombotic burden compared to current standard of care whilst being clinically safe. • RETRIEVE-AMI is an investigator-initiated, single centre, randomised, proof-of-concept pilot trial. • The efficacy and safety of stent retriever will be evaluated in STEMI with high thrombus burden. • 81 participants admitted for primary PCI for inferior STEMI will be enrolled. • The primary endpoint is the degree of thrombus burden reduction assessed by OCT. • The co-primary endpoint is the safety of stent-retriever-based thrombectomy. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is an important risk factor for adverse outcomes following acute myocardial infarction (AMI), but large-scale studies investigating the differential impact of Type 1 DM (T1DM) and Type 2 DM (T2DM) on AMI outcomes are lacking. All adult discharges for AMI in the National Inpatient Sample (October 2015 to December 2018) were included and stratified into T1DM, T2DM and non-DM (NDM) groups. Outcomes of interests were all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE), major bleeding and acute ischemic stroke, as well as invasive management. Binomial hierarchical multilevel multivariable logistic regression with adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) was used to investigate the association between DM and its subtypes with the AMI outcomes. Out of 2,587,615 patients, there were 29,250 (1.1 %) T1DM and 1,032,925 (39.9 %) T2DM patients. After multivariable adjustment, patients with T1DM had increased odds of MACCE (aOR 1.20, 95 % CI 1.09–1.31), all-cause mortality (aOR 1.20, 95 % CI 1.08–1.33) and major bleeding (aOR 1.28, 95 % CI 1.13–1.44), whilst T2DM patients had increased odds of MACCE (aOR 1.03, 95 % CI 1.01–1.05) and ischemic stroke (aOR 1.09, 95 % CI 1.05–1.13), compared to NDM patients. The adjusted odds of receiving percutaneous coronary intervention were lower in both T1DM and T2DM patients (aOR 0.70, 95 % CI 0.66–0.75 and aOR 0.95, 95 % CI 0.94–0.96, respectively), but T2DM patients showed higher utilization of composite percutaneous and surgical revascularization (aOR 1.03, 95 % CI 1.03–1.04) compared to NDM patients. DM patients presenting with AMI have worse in-hospital clinical outcomes compared to NDM patients. There are important DM type-related differences with T1DM patients having overall worse outcomes and receiving less overall revascularization. [Display omitted] • Differential impact of diabetes mellitus (DM) types on acute myocardial infarction (AMI) outcomes is not well-defined. • DM patients with AMI have lower adjusted utilization of invasive management compared to patients without DM. • DM patients with AMI have worse adjusted clinical outcomes compared to patients without DM. • There are important DM type-related differences with Type 1 DM patients having overall worse outcomes. [ABSTRACT FROM AUTHOR]

Despite early and currently effective epicardial coronary recanalization, the mortality rate after mechanical complication (MC) remains high, especially in cardiogenic shock. There is an increase in the use of mechanical circulatory support in patients with cardiogenic shock and MC, however, evidence is still scarce and most studies exclude patients with mechanical complications. Using the National Inpatient Sample database from 2015 to 2018 to identify patients with AMI, we aimed to determine the predictors and outcomes of patients with MC, subtypes and the use of MCS. We identified 2,427,315 patients with AMI; 2345 (0.1 %) developed MC and of them 1320 (56.3 %) received MCS. Regarding subtypes, 960 (40.9 %) had ventricular septal rupture (VSR), 540 (23.0 %) papillary muscle rupture (PMR), 530 (22.6 %) pseudoaneurysm, and 315 (13.4 %) free wall rupture (FWR). Mortality was 12 times higher (OR: 11.663, CI: 10.582–12.855, p < 0.001) in patients with MC compared to patients without MC (49.7 % vs. 4.6 %, p < 0.001) and all subtypes of MC showed a significant increase in mortality. The use of MCS was associated with decreased mortality in PMR (46.2 % to 34.8 %, p = 0.009) and pseudoaneurysm (64.7 % to 42.1 %, p < 0.001), however, with higher mortality in VSR. The incidence of MC after an AMI is very low, nonetheless the in-hospital mortality rate remains very high. It tends to occur more in older patients and with fewer comorbidities. The subtype with the highest frequency and highest mortality was VSR. The use of mechanical circulatory support was associated with better survival in PMR and pseudoaneurysm, but not overall survival. • Currently, despite rapid and effective epicardial coronary reperfusion, mechanical complications following AMI continue to be the most devastating and frightening complications, albeit with a very low incidence of 0.1%. • Positive predictors of having a mechanical complication are older age, female sex, fewer medical comorbidities, STEMI presentation, heart failure and nonischemic heart conditions such as valve disease and atrial fibrillation. • The mortality of patients with AMI and MC is 12 times higher than that of patients without MC (49.7 % vs. 4.6 %) and all subtypes of MC showed a significant increase in mortality. • The use of mechanical circulatory support is associated with decreased mortality in papillary muscle rupture and pseudoaneurysm, with no difference in free wall rupture, however, with higher mortality in ventricular septal rupture. [ABSTRACT FROM AUTHOR]

Despite the evolution of stent technology, there is a non-negligible risk of in-stent restenosis (ISR) after Percutaneous coronary intervention (PCI). Large-scale registry data on the prevalence and clinical management of ISR is lacking. The aim was to describe the epidemiology and management of patients with ≥1 ISR lesions treated with PCI (ISR PCI). Data on characteristics, management and clinical outcomes were analyzed for patients undergoing ISR PCI in the France-PCI all-comers registry. Between January 2014 and December 2018, 31,892 lesions were treated in 22,592 patients, 7.3 % of whom underwent ISR PCI. Patients undergoing ISR PCI were older (68.5 vs 67.8; p < 0.001), and more likely to have diabetes (32.7 % vs 25.4 %, p < 0.001), chronic coronary syndrome or multivessel disease. ISR PCI concerned drug eluting stents (DES) ISR in 48.8 % of cases. Patients with ISR lesions were more frequently treated with DES than drug eluting balloon or balloon angioplasty (74.2 %, 11.6 % and 12.9 %, respectively). Intravascular imaging was rarely used. At 1 year, patients with ISR had higher target lesion revascularization rates (4.3 % vs. 1.6 %; HR 2.24 [1.64–3.06]; p < 0.001). In a large all-comers registry, ISR PCI was not infrequent and associated with worse prognosis than non-ISR PCI. Further studies and technical improvements are warranted to improve the outcomes of ISR PCI. Abbreviations: DEB: drug eluting balloon; DES: drug eluting stent; HR: hazard ratio; POBA: plain old balloon angioplasty; ISR: in-stent restenosis; TLR: target lesion revascularization. [Display omitted] • ISR PCI is performed with relevant frequency in routine clinical practice (7-8%). • Approximately 10-20% of ISR are treated with POBA. • Intravascular imaging is largely underused (< 2%). • At 1 year, patients with ISR PCI have higher TLR rates than non-ISR PCI (4.3% vs. 1.6%; HR 2.24 [1.64-3.06]; p <0.001). [ABSTRACT FROM AUTHOR]

This meta-analysis aimed to examine the association of child abuse with adult coronary heart disease risk and separately by abuse subtypes, including emotional abuse, sexual abuse, and physical abuse. Data were extracted from studies published up through December 2021 and on the basis of research from PubMed, Embase, CINAHL, and PsycINFO. Studies were selected if they included adults with or without any type of child abuse and measured the risk of any type of coronary heart disease. Statistical analyses were conducted in 2022. The random effects model was used to pool the effect estimates presented by RRs with 95% CIs. Heterogeneity was assessed using Q and I2 statistics. The pooled estimates were synthesized using 24 effect sizes from 10 studies with a sample size of 343,371 adults. Adults with child abuse were associated with a higher risk of coronary heart disease than those without (RR=1.52; 95% CI=1.29, 1.79), and the association was similar for myocardial infarction (RR=1.50; 95 % CI=1.08, 2.10) and unspecified coronary heart disease (RR=1.58; 95% CI=1.23, 2.02). Moreover, emotional (RR=1.48; 95% CI=1.29, 1.71), sexual (RR=1.47; 95% CI=1.15, 1.88), and physical (RR=1.48; 95% CI=1.22, 1.79) abuse were associated with increased risk of coronary heart disease. Child abuse was associated with an increased risk of adult coronary heart disease. Results were generally consistent across abuse subtypes and sex. This study advocates further research on biological mechanisms linking child abuse to coronary heart disease as well as improvement in coronary heart disease risk prediction and targeted prevention approaches. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify whether the association of gait speed with the incidence of cardiovascular disease depends on baseline glycemic status. This retrospective observational cohort study used the Japan Medical Data Center Claims Database between 2005 and 2021 and analyzed 3,090,048 participants without a cardiovascular disease history. The median (IQR) age was 44 (37–53) years, and 1,755,205 of the participants (56.8%) were men. Information on gait speed was obtained from self-reported questionnaires in health checkups. Study participants were categorized according to HbA1c levels (<5.7%, 5.7–6.4%, and ≥6.5%). The primary endpoint was defined as a composite cardiovascular disease outcome that consists of heart failure, myocardial infarction, angina pectoris, and stroke. During the mean follow-up period of 1,120±857 days, 116,678 composite cardiovascular disease outcomes were documented. Self-reported fast gait speed was related to a lower risk of developing cardiovascular disease; this relationship was more pronounced with increasing HbA1c levels. Compared with slow gait speed, the hazard ratio (95% CI) of self-reported fast gait speed for cardiovascular disease was 0.935 (0.921–0.949) in participants with an HbA1c <5.7%, 0.911 (0.891–0.932) in participants with an HbA1c of 5.7–6.4%, and 0.846 (0.811–0.883) in participants with HbA1c ≥6.5% (p -value for interaction<0.001). The relationship of subjective gait speed with the risk of cardiovascular disease was amplified in individuals with prediabetes or diabetes mellitus, suggesting that maintaining exercise capacity could be more important in individuals with impaired glucose tolerance for preventing cardiovascular disease. [ABSTRACT FROM AUTHOR]

Quality measures within Emergency Medicine (EM) were developed to standardize and improve care. Their development has been limited by lack of consideration of sex- and gender-based differences. Research has suggested that sex and gender can impact clinical care and treatment. Inclusion of sex and gender differences is needed to create EM quality measures that are equitable to all. The aim of the review is to provide a brief history of EM quality measures and the value of considering sex- and gender-based evidence in their development to ensure equity, using acute myocardial infarction (AMI) as an example. Current quality measures related to AMI, such as time-to-electrocardiogram and door-to-balloon time in percutaneous coronary intervention, may have important and modifiable disparities when stratified by sex. Even when presenting with signs and symptoms of AMI, women experience delayed time to diagnosis and treatment. Few studies have considered interventions to mitigate these differences. However, the data available suggest that sex-based disparities can be minimized by implementation of strategies such as a quality control checklist. Quality measures were created to deliver high-quality, evidence-based, and standardized care, but without the inclusion of sex and gender metrics, they may not advance care to an equitable level. [ABSTRACT FROM AUTHOR]

Patients with acute coronary syndromes (ACS) remain at risk of cardiovascular disease (CVD) recurrences. Peripheral artery disease (PAD) may identify a very high risk (VHR) group who may derive greater benefit from intensified secondary prevention. Among ACS-patients enrolled in the prospective multi-center Special Program University Medicine (SPUM), we assessed the impact of PAD on major cardiovascular events (MACE: composite of myocardial infarction, stroke and all-cause death) and major bleeding. Multivariate analysis tested the relation of each significant variable with MACE, as well as biomarkers of inflammation and novel markers of atherogenesis. Out of 4787 ACS patients, 6.0% (n = 285) had PAD. PAD-patients were older (p < 0.001), with established CVD and signs of increased persistent inflammation (hs-CRP; 23.6 ± 46.5 vs 10.4 ± 27.2 mg/l, p < 0.001 and sFlt-1; 1399.5 ± 1501.3 vs 1047.2 ± 1378.6 ng/l, p = 0.018). In-hospital-death (3.2% vs 1.4%, p = 0.022) and -MACE (5.6% vs 3.0%, p = 0.017) were higher in PAD-patients. MACE at 1 year (18.6% vs 7.9%,p < 0.001) remained increased even after adjustment for confounders (Adj. HR 1.53, 95% CI: 1.14–2.08, p = 0.005). Major bleeding did not differ between groups (Adj. HR 1.18; 95% CI 0.71–1.97, p = 0.512). Although PAD predicted MACE, PAD-patients were prescribed less frequently for secondary prevention at discharge. In this real-world ACS patient cohort, concomitant PAD is a marker of VHR and is associated with increased and persistent inflammation, higher risk for MACE without an increased risk of major bleeding. Therefore, a history of PAD may be useful to identify those ACS patients at VHR who require more aggressive secondary prevention. • PAD is an easy identifiable marker of residual very high risk in ACS. • PAD in ACS is associated with increased risk of MACE but not of major bleeding. • PAD patients presented persistent increased inflammation. • PAD patients are often undertreated despite a higher residual risk. [ABSTRACT FROM AUTHOR]

Wellens syndrome is a well-known clinical syndrome characterized by specific electrocardiographic (ECG) patterns that is usually suggestive of a critical proximal left anterior descending (LAD) coronary artery stenosis and requires early revascularization. There are two Wellens ECG patterns (A and B) described in the literature. It was suggested that Wellens syndrome can evolve from pattern A into pattern B, however, there is paucity of reported cases that described this phenomena. We report a case of Wellens syndrome that initially presented with very subtle ECG T wave changes suggestive of Wellens pattern A that progressed into classic pattern B with T wave inversions. A very low threshold of suspicion and serial ECGs were imperative to the early recognition of such a critical cardiovascular disease. • We report a case of Wellens syndrome that initially presented with very subtle ECG. • T wave changes suggestive of Wellens pattern A that progressed into classic pattern B with T wave inversions. • A very low threshold of suspicion and serial ECGs were imperative to the early recognition of such a critical cardiovascular disease. [ABSTRACT FROM AUTHOR]

There are multiple reported injuries associated with cardiopulmonary resuscitation, most of them caused by the force of compressions, like sternal and rib fractures, abdominal organ injuries like splenic rupture, liver lacerations, and injuries to the upper airway and skin. Injuries related to defibrillation and cardioversion are rare, mostly related to skin and muscle injuries on where the defibrillation paddles were placed. A 52-year-old man presented to the Emergency Department with crushing chest pain. The patient was suffering from a myocardial infarction, and during percutaneous coronary intervention, had to be defibrillated on the angioplasty table. This resulted in fracture–dislocations on both shoulders. The patient was transferred to our orthopedics clinic and was operated on within 5 days of angioplasty. Early diagnosis and treatment are important, and can prevent long-term morbidity. However, cardiopulmonary resuscitation and defibrillation are acts that are most commonly performed in the emergency department. Injury prevention by controlling the patient's position, in this case, positions of the shoulders, is an important factor that emergency physicians can control and effect. [ABSTRACT FROM AUTHOR]

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[Display omitted] [ABSTRACT FROM AUTHOR]

Risk of atherothrombotic events is not uniform in patients with type 2 diabetes mellitus (T2DM). Tailored risk assessment may help guide selection of pharmacotherapies for cardiovascular primary and secondary prevention. The purpose of this study was to develop a risk model for atherothrombosis in patients with T2DM. We developed and validated a risk model for myocardial infarction (MI) or ischemic stroke (IS) in a pooled cohort of 42,181 patients with T2DM from 4 TIMI (Thrombolysis In Myocardial Infarction) clinical trial cohorts. Candidate variables were assessed with multivariable Cox regression, and independent variables (P < 0.05) were retained in the final model. Discrimination and calibration were assessed. Treatment interactions with dapagliflozin (sodium-glucose cotransporter-2 inhibitor) and evolocumab (proprotein convertase subtilisin/kexin type 9 inhibitor) were explored in the DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis In Myocardial Infarction 58) and FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trials, respectively. Sixteen variables were independent predictors of MI or IS. The model identified a >8-fold gradient of MI or IS rates between the top vs bottom risk quintiles in the validation cohort (3-year Kaplan-Meier rate: 14.9% vs 1.4%; P < 0.0001). C-indexes were 0.704 and 0.706 in the derivation and validation cohorts, respectively. The model was well-calibrated in both primary and secondary prevention. Absolute reduction in the rates of MI or IS tended to be greater in patients with higher baseline predicted risk for both dapagliflozin (absolute risk reduction: 2.1% vs 0.2%) and evolocumab (absolute risk reduction: 3.2% vs 1.0%). We developed and validated a risk score for atherothrombotic events, leveraging 16 routinely assessed clinical variables in patients with T2DM. The score has the potential to improve risk assessment and inform clinical decision-making. [Display omitted] [ABSTRACT FROM AUTHOR]

Previous studies have failed to show a cardioprotective benefit of beta-blockers in patients with stable coronary artery disease (CAD). This study sought to determine the association between beta-blockers and cardiovascular events in patients with stable CAD using a new user design. All patients aged >66 years undergoing elective coronary angiography in Ontario, Canada, from 2009 to 2019 with diagnosed obstructive CAD were included. Exclusion criteria included heart failure or a recent myocardial infarction, as well as having a beta-blocker prescription claim in the previous year. Beta-blocker use was defined as having at least 1 beta-blocker prescription claim in the 90 days preceding or after the index coronary angiography. The main outcome was a composite of all-cause mortality and hospitalization for heart failure or myocardial infarction. Inverse probability of treatment weighting using the propensity score was used to account for confounding. This study included 28,039 patients (mean age: 73.0 ± 5.6 years; 66.2% male), and 12,695 of those (45.3%) were newly prescribed beta-blockers. The 5-year risks of the primary outcome were 14.3% in the beta-blocker group and 16.1% in the no beta-blocker group (absolute risk reduction: −1.8%; 95% CI: −2.8 to −0.8; HR: 0.92; 95% CI: 0.86-0.98 ; P = 0.006). This result was driven by reductions in myocardial infarction hospitalization (cause-specific HR: 0.87; 95% CI: 0.77-0.99 ; P = 0.031), whereas no differences were observed in all-cause death or heart failure hospitalization. In patients with angiographically documented stable CAD without heart failure or a recent myocardial infarction, beta-blockers were associated with a small but significant reduction in cardiovascular events at 5 years. [Display omitted] [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Outcome has improved during the last decades due to secondary prevention and widespread coronary interventions, but recent studies still show sex differences and insufficient drug adherence. We aimed to determine differences in the treatment strategies and outcomes between women and men with ST-elevation myocardial infarction (STEMI) in Germany. From the Federal Association of the Local Health Insurance Funds (Allgemeine Ortskrankenkasse), 175,187 patients were identified who were hospitalized due to STEMI in Germany between January 1, 2010 and December 31, 2017. Compared to men, women were older (median 76 vs. 64 years) and had more often diabetes, hypertension, chronic heart failure, and chronic kidney disease (all p < 0.001). Women suffered from higher rates of in-hospital complications such as bleeding (9.3 vs. 6.6%), longer hospitalizations (12.2 vs. 11.7 days) and were less likely to undergo percutaneous coronary intervention (75.5 vs. 85.2%). After adjustment for patient's risk profile, female sex was associated with decreased overall survival (HR 1.02, 95% confidence interval (CI) 1.00–1.04; p= 0.036). Notably, more men received all four guideline-recommended drugs after STEMI (women 65.7% vs. men 69.8% after 90 days; p < 0.001). With increasing number of prescribed drugs, patients benefit even more. This concerned both sexes, but was more pronounced in men (with 4 prescribed drugs: women HR 0.52, 95%CI 0.50–0.55; men HR 0.48, 95% CI 0.47–0.50, p int = 0.014). In a contemporary nationwide analysis, women with STEMI were older, had more comorbidities, underwent revascularization less often and had an increased risk for major complications as well as overall survival. Guideline-recommended drug therapy was applied less frequently in women although associated with an improved overall-survival. [Display omitted] • Compared to men, women with STEMI were older and had more comorbidities. • Women had higher rates of inpatient complications, received percutaneous coronary intervention less often, and when adjusted for the risk profile, the female sex was associated with reduced overall survival. • After STEMI, women received all four guideline-recommended drugs less often, although the prognosis improved with the increase in these drugs. [ABSTRACT FROM AUTHOR]

Depression and anxiety are risk factors for patients with myocardial infarction (MI). However, the association of a previous psychiatric diagnosis of anxiety or depression, or only such self-reported symptoms, with cardiovascular outcomes and mortality post-MI has not been previously examined in the same nationwide cohort. We linked demographic, socioeconomic and clinical data from four nationwide Swedish registries for patients enrolled in cardiac rehabilitation (CR) after first-time MI (2006–2015, N = 45,096). After multiple imputation, we applied Cox regression to estimate the post-MI outcome risk for patients with a previous psychiatric diagnosis of anxiety/depression (Diagnosis), patients with no formal diagnosis but self-reported symptoms of anxiety/depression (Symptoms), versus patients with neither Diagnosis nor Symptoms (Reference). During one-year follow-up, fully adjusted models showed that patients with Diagnosis had a higher risk (hazard ratio [95%CI]) of all-cause mortality (1.86 [1.36, 2.53]), reinfarction (1.14 [1.06, 1.22]), their composite (1.15 [1.07, 1.23]), and an extended cardiovascular composite (1.19 [1.12, 1.26]), versus Reference, even though 77% reported no symptoms at the time of MI. In patients with Symptoms, estimates were also elevated yet somewhat attenuated compared to Reference. Findings were overall robust across multiple sensitivity analyses. Both a previous diagnosis, and present self-reported symptoms of anxiety or depression are associated with an increased risk of death and recurrent cardiovascular events in adults with first-time MI. Only screening for present symptoms is inadequate for assessing this excessive risk. Assessment of both psychiatric history and self-reported symptoms seems warranted for these patients. [Display omitted] • Depression and anxiety are risk factors for patients with myocardial infarction (MI) • Different operationalisations of depression and anxiety and their association with post MI risk have not been studied in the same nationwide cohort. • We linked demographic, socioeconomic and clinical data from four nationwide Swedish registries for 45,096 SWEDEHEART patients enrolled in cardiac rehabilitation (CR) after first-time MI. • We estimated the post-MI risk of death and cardiovascular events for patients with (1) a previous psychiatric diagnosis of anxiety or depression, (2) no such diagnosis but instead present symptoms of anxiety or depression, vs (3) patients with neither diagnosis nor symptoms. • Both a previous diagnosis, and symptoms of anxiety or depression were associated with an increased risk of death and recurrent cardiovascular events in adults with first-time MI. • Only screening for present symptoms is inadequate for assessing this excessive risk in patients with first-time MI. • Assessment of both psychiatric history and self-reported symptoms seems warranted for patients with first-time MI. [ABSTRACT FROM AUTHOR]

Mortality rates following cardiogenic shock (CS) have stagnated on an unacceptably high level. Limited data regarding the prognostic value of sex in patients suffering from CS is available. Therefore, this study aims to investigate the prognostic value of sex in patients with CS. Consecutive patients with CS of any cause were included from 2019 to 2021. Prognosis of females was compared to males regarding 30-day all-cause mortality. Further risk stratification was performed according to the presence or absence of CS related to acute myocardial infarction (AMI). Kaplan-Meier and multivariable Cox proportional regression analyses were applied for statistics. From a total of 273 CS patients (AMI-CS: 49%; non-AMI-CS: 51%), 60% were males and 40% females. The risk of 30-day all-cause mortality did not differ among males and females (56% vs. 56%; log rank p = 0.775; HR = 1.046; 95% CI 0.756–1.447; p = 0.785). Even after multivariable adjustment, sex was not associated with prognosis in CS patients (HR = 1.057; 95% CI 0.713–1.564; p = 0.784). Comparable risks of short-term mortality in both sexes were observed irrespective of the presence of AMI-related CS (64.0% vs. 64.6%; log rank p = 0.642; HR = 1.103; 95% CI 0.710–1.713; p = 0.664) and non-AMI-related CS (46.2% vs. 49.2%; log rank p = 0.696; HR = 1.099; 95% CI 0.677–1.783; p = 0.704). Sex was not associated with the risk of 30-day all-cause mortality in CS patients irrespective of CS etiology. (clinicaltrials.gov identifier: NCT05575856) • The study investigates the prognostic role of sex-related outcomes in patients with cardiogenic shock (CS) • The rates of CS related to acute myocardial infarction (AMI) were higher in males. • In contrast, the risk of 30-day all-cause mortality did not differ among males and females. • Mortality was comparable irrespective of AMI-related CS or non-AMI-related CS. [ABSTRACT FROM AUTHOR]

Atherosclerotic plaque ruptures, triggered by blood flow–associated biomechanical forces, cause most myocardial infarctions and strokes. This study aims to investigate the exact location and underlying mechanisms of atherosclerotic plaque ruptures, identifying therapeutic targets against cardiovascular events. Histology, electron microscopy, bulk and spatial RNA sequencing on human carotid plaques were studied in proximal, most stenotic, and distal regions along the longitudinal blood flow direction. Genome-wide association studies were used to examine heritability enrichment and causal relationships of atherosclerosis and stroke. Associations between top differentially expressed genes (DEGs) and preoperative and postoperative cardiovascular events were examined in a validation cohort. In human carotid atherosclerotic plaques, ruptures predominantly occurred in the proximal and most stenotic regions but not in the distal region. Histologic and electron microscopic examination showed that proximal and most stenotic regions exhibited features of plaque vulnerability and thrombosis. RNA sequencing identified DEGs distinguishing the proximal and most stenotic regions from the distal region which were deemed as most relevant to atherosclerosis-associated diseases as shown by heritability enrichment analyses. The identified pathways associated with the proximal rupture-prone regions were validated by spatial transcriptomics, firstly in human atherosclerosis. Of the 3 top DEGs, matrix metallopeptidase 9 emerged particularly because Mendelian randomization suggested that its high circulating levels were causally associated with atherosclerosis risk. Our findings show plaque site–specific transcriptional signatures associated with proximal rupture-prone regions of carotid atherosclerotic plaques. This led to the geographical mapping of novel therapeutic targets, such as matrix metallopeptidase 9, against plaque rupture. [Display omitted] [ABSTRACT FROM AUTHOR]

Electrical storm (ES) reflects life-threatening cardiac electrical instability with 3 or more ventricular arrhythmia episodes within 24 hours. Identification of underlying arrhythmogenic cardiac substrate and reversible triggers is essential, as is interrogation and programming of an implantable cardioverter-defibrillator, if present. Medical management includes antiarrhythmic drugs, beta-adrenergic blockade, sedation, and hemodynamic support. The initial intensity of these interventions should be matched to the severity of ES using a stepped-care algorithm involving escalating treatments for higher-risk presentations or recurrent ventricular arrhythmias. Many patients with ES are considered for catheter ablation, which may require the use of temporary mechanical circulatory support. Outcomes after ES are poor, including frequent ES recurrences and deaths caused by progressive heart failure and other cardiac causes. A multidisciplinary collaborative approach to the management of ES is crucial, and evaluation for heart transplantation or palliative care is often appropriate, even for patients who survive the initial episode. [Display omitted] • ES is a life-threatening condition characterized by recurrent VAs. • Management of patients with ES integrates antiarrhythmic drugs, beta-blockade, sedation, and catheter ablation. • Comprehensive evidence-based treatment algorithms are needed to define best practices for managing patients with ES. [ABSTRACT FROM AUTHOR]

• Tricyclic antidepressants significantly decrease cardiac parasympathetic activity. • Selective serotonin reuptake inhibitors (SSRIs) reduce skin conductance response. • SSRIs have insignificant or inconclusive effects on heart rate variability. • Agomelatine has a beneficial effect on cardiac autonomic regulation. Changes in cardiac autonomic nervous system (ANS) regulation observed in psychiatric disorders may be mitigated by antidepressants. We meta-analyzed and systematically reviewed studies examining antidepressants' effects on ANS outcomes, including heart rate variability (HRV). We conducted a PRISMA/MOOSE-compliant search of PubMed and Scopus until March 28th, 2022. We included randomized placebo-controlled trials (RCTs) and pre-post studies, regardless of diagnosis. We pooled results in random-effects meta-analyses, pooling homogeneous study designs and outcomes. We conducted sensitivity analyses and assessed quality of included studies. Thirty studies could be meta-analyzed. Selective serotonin reuptake inhibitors (SSRIs) were significantly associated with a reduction in the square root of the mean-squared difference between successive R-R intervals (RMSSD) (SMD= -0.48) and skin conductance response (SMD= -0.55) in RCTs and with a significant increase in RMSSD in pre-post studies (SMD=0.27). In pre-post studies, tricyclic antidepressants (TCAs) were associated with a significant decrease in several HRV outcomes while agomelatine was associated with a significant increase in high frequency power (SMD= 0.14). In conclusion, SSRIs reduce skin conductance response but have no or inconclusive effects on other ANS outcomes, depending on study design. TCAs reduce markers of parasympathetic function while agomelatine might have the opposite effect. Studies are needed to investigate the impact of SSRIs on the recovery of cardiac ANS regulation after acute myocardial infarction, and the effects of newer antidepressants. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists. Patients with PCa receiving GnRH agonists or antagonists during 2013–2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACE PRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACE CVM , i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups. In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0–81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7–5.0 years), 1115 patients (45.0%) had MACE PRONOUNCE and 344 (13.9%) had MACE CVM. GnRH agonist users had lower risks of MACE PRONOUNCE (Log-rank P < 0.001) and MACE CVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACE PRONOUNCE : Log-rank P = 0.308; MACE CVM : Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACE PRONOUNCE (Log-rank P < 0.001) and MACE CVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACE PRONOUNCE : Log-rank P = 0.569; MACE CVM : Log-rank P = 0.615). GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors. • GnRH agents may differ in cardiovascular safety. • 2479 prostate cancer patients receiving GnRH agonists or antagonist were studied. • GnRH antagonist may be associated with higher long-term cardiovascular risks. • Short-term cardiovascular risks did not differ between GnRH agonists and antagonists. • Those without cardiovascular risk factors had a larger increase in long-term risks. [ABSTRACT FROM AUTHOR]

High sensitivity troponin (hs-cTn) and diagnostic algorithms are used to rapidly triage patients with symptoms of acute myocardial infarction in emergency departments (ED). However, few studies have evaluated the impact of simultaneously implementing hs-cTn and a rapid rule-out algorithm on length of stay (LOS). We assessed the impact of transitioning from contemporary cTnI to hs-cTnI in 59,232 ED encounters over three years. hs-cTnI was implemented with an orderable series that included baseline, two-, four-, and six-hour specimens collected at provider discretion and operationalized with an algorithm to calculate the change in hs-cTnI from baseline and provide interpretations of "insignificant", "significant," or "equivocal." Patient demographics, results, chief complaint, disposition, and ED LOS were captured from the electronic medical record. cTnI was ordered for 31,875 encounters prior to hs-cTnI implementation and 27,357 after. The proportion of cTnI results above the 99th percentile upper reference limit decreased from 35.0% to 27.0% for men and increased from 27.8% to 34.8% for women. Among discharged patients, the median LOS decreased by 0.6 h (0.5–0.7). LOS among discharged patients with a chief complaint of chest pain decreased by 1.0 h (0.8–1.1) and further decreased by 1.2 h (1.0–1.3) if the initial hs-cTnI was below the limit of quantitation. The rate of acute coronary syndrome upon re-presentation within 30 days did not change post-implementation (0.10% versus 0.07%). Implementation of an hs-cTnI assay with a rapid rule-out algorithm decreased ED LOS among discharged patients, particularly among those with a chief complaint of chest pain. [ABSTRACT FROM AUTHOR]

The cardiac damage biomarkers cardiac troponin T (cTnT) and troponin I (cTnI) are used to identify patients with myocardial infarction (MI). To make the correct clinical decisions it is important to identify false positive results due to troponin assay interference. Often interferences are caused by high-molecular weight immunocomplexes called macrotroponin that may result in false troponin elevations because of delayed troponin clearance, or heterophilic antibodies that crosslink troponin assay antibodies and generate troponin-independent signals. We describe and compare four methods for cTnI assay interference analysis using a protein G spin column method, gel filtration chromatography and two versions of a sucrose gradient ultracentrifugation for cTnI assay interference analysis on five patients with confirmed cTnI interference and one MI patient without cTnI interference from our troponin interference referral center. The protein G spin column method had a high between run variability but was still able to identify all five patients with cTnI interference. The sucrose gradient ultracentrifugation methods and the gel filtration method had simlar performancec and correctly identified the immunocomplexes that caused the cTnI interference. Our experience is that these methods are sufficient to safely confirm or exclude positive cTnI assay interference. [ABSTRACT FROM AUTHOR]

Clinical presentation of Takotsubo Syndrome (TS) mimics acute coronary syndrome (ACS). A score to differentiate TS from ACS would be helpful to facilitate appropriate investigation and management. We have previously developed a clinical score (NSTE-Takotsubo Score) to distinguish women with non-ST-segment elevation myocardial infarction (NSTEMI) from TS with non-ST-segment elevation (NSTE-TS). This study sought to assess the diagnostic validity of this score in an external validation cohort. The external cohort consisted of women with NSTE-TS (n=110) and NSTEMI (n=113) from two major tertiary hospitals in New Zealand. The five variables in the arithmetic score (range -6 to +5) and their relative weights are: T-wave inversion (TWI) in ≥6 leads (3 points), recent stress (2 points), diabetes mellitus (DM) (-1 point), prior cardiovascular disease (CVD) (-2 points) and presence of ST depression (-3 points). Two clinicians blinded to the diagnoses calculated the score using clinical and electrocardiogram (ECG) data on day 1 post-admission. The NSTE-Takotsubo Score discriminated well between NSTE-TS and NSTEMI. The sensitivity and specificity of a score ≥1 to distinguish NSTE-TS from NSTEMI were 78% and 85%, respectively. The area under the receiver operator curve was 0.78 (95% CI 0.72 to 0.84). In an external validation cohort, the NSTE-Takotsubo Score was easy to apply and useful to identify women likely to have NSTE-TS on day 1 post-admission. [ABSTRACT FROM AUTHOR]

Previous studies examining temporal variations in cardiovascular care have largely been limited to assessing weekend and after-hours effects. We aimed to determine whether more complex temporal variation patterns might exist in chest pain care. This was a population-based study of consecutive adult patients attended by emergency medical services (EMS) for non-traumatic chest pain without ST elevation in Victoria, Australia between 1 January 2015 and 30 June 2019. Multivariable models were used to assess whether time of day and week stratified into 168 hourly time periods was associated with care processes and outcomes. There were 196,365 EMS chest pain attendances; mean age 62.4 years (standard deviation [SD] 18.3) and 51% females. Presentations demonstrated a diurnal pattern, a Monday–Sunday gradient (Monday peak) and a reverse weekend effect (lower rates on weekends). Five temporal patterns were observed for care quality and process measures, including a diurnal pattern (longer emergency department [ED] length of stay), an after-hours pattern (lower angiography or transfer for myocardial infarction, pre-hospital aspirin administration), a weekend effect (shorter ED clinician review, shorter EMS off-load time), an afternoon/evening peak period pattern (longer ED clinician review, longer EMS off-load time) and a Monday–Sunday gradient (ED clinician review, EMS offload time). Risk of 30-day mortality was associated with weekend presentation (Odds ratio [OR] 1.15, p=0.001) and morning presentation (OR 1.17, p<0.001) while risk of 30-day EMS reattendance was associated with peak period (OR 1.16, p<0.001) and weekend presentation (OR 1.07, p<0.001). Chest pain care demonstrates complex temporal variation beyond the already established weekend and after-hours effect. Such relationships should be considered during resource allocation and quality improvement programs to improve care across all days and times of the week. [ABSTRACT FROM AUTHOR]

The pleiotropic action of ticagrelor, with effects in addition to platelet inhibition, has been shown to improve endothelial function in patients with coronary artery disease. These positive effects are possibly adenosine mediated. This study investigated the association of ticagrelor therapy and coronary artery flow reserve in survivors of myocardial infarction (MI). This was an exploratory, cross-sectional, open substudy of PROFLOW. High-risk individuals with a history of MI were identified. Coronary flow reserve (CFR) was measured non-invasively in the left anterior descending artery using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperaemia by intravenous infusion of adenosine at 140 μg/kg/min. Patients receiving ticagrelor (n=75) were compared with those not receiving ticagrelor (n=506), using simple and multiple linear regression models. Most patients in both groups were treated with aspirin (97% in the ticagrelor and 94% in the non-ticagrelor group). Adjustment for traditional risk factors was conducted. The mean age at study inclusion was 68.5±6.8 years, and most patients were male (81.8%). The simple linear regression analysis showed ticagrelor treatment to be significantly associated with increased CFR: ticagrelor 2.95±0.76 (mean±SD), non-ticagrelor 2.70±0.77, (coefficient 0.25; 95% CI 0.063–0.438; p=0.009). This association was significant in two of the three multiple linear regression models with increasing numbers of variables: Model 1 (0.28; 0.06–0.50; p=0.014), Model 2 (0.26; 0.03–0.48; p=0.025), and borderline significant in Model 3 (0.21; –0.01 to 0.43; p=0.058). Ticagrelor treatment was associated with increased CFR in this high-risk population. Increased CFR may be a clinically important therapeutic effect of ticagrelor in addition to platelet inhibition. [ABSTRACT FROM AUTHOR]

Transplanting human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) tissue sheets effectively treat ischemic cardiomyopathy. Cardiac functional recovery relies on graft survival in which angiogenesis played an important part. ONO-1301 is a synthetic prostacyclin analog with proangiogenic effects. We hypothesized that transplantation of hiPSC-CM tissue sheets with slow-release ONO-1301 scaffold could promote hostgraft angiogenesis, enhance tissue survival and therapeutic effect. We developed hiPSC-CM tissue sheets with ONO-1301 slow-release scaffold and evaluated their morphology, gene expression, and effects on angiogenesis. Three tissue sheet layers were transplanted into a rat myocardial infarction (MI) model. Left ventricular ejection fraction, gene expression in the MI border zone, and angiogenesis effects were investigated 4 weeks after transplantation. In vitro assessment confirmed the slow-release of ONO-1301, and its pro-angiogenesis effects. In addition, in vivo data demonstrated that ONO-1301 administration positively correlated with graft survival. Cardiac tissue as thick as ∼900 μm was retained in the ONO (+) treated group. Additionally, left ventricular ejection fraction of the ONO (+) group was significantly enhanced, compared to ONO (−) group. The ONO (+) group also showed significantly improved interstitial fibrosis, higher capillary density, increased number of mature blood vessels, along with an enhanced supply of oxygen, and nutrients. Slow-release ONO-1301 scaffold provided an efficient delivery method for thick hiPSC-CM tissue. ONO-1301 promotes angiogenesis between the host and graft and improves nutritional and oxygen supply, thereby enhancing the survival of transplanted cells, effectively improving ejection fraction, and therapeutic effects. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Outcome has improved during the last decades due to secondary prevention and widespread coronary interventions, but recent studies still show sex differences and insufficient drug adherence. We aimed to determine differences in the treatment strategies and outcomes between women and men with ST-elevation myocardial infarction (STEMI) in Germany. From the Federal Association of the Local Health Insurance Funds (Allgemeine Ortskrankenkasse), 175,187 patients were identified who were hospitalized due to STEMI in Germany between January 1, 2010 and December 31, 2017. Compared to men, women were older (median 76 vs. 64 years) and had more often diabetes, hypertension, chronic heart failure, and chronic kidney disease (all p < 0.001). Women suffered from higher rates of in-hospital complications such as bleeding (9.3 vs. 6.6%), longer hospitalizations (12.2 vs. 11.7 days) and were less likely to undergo percutaneous coronary intervention (75.5 vs. 85.2%). After adjustment for patient's risk profile, female sex was associated with decreased overall survival (HR 1.02, 95% confidence interval (CI) 1.00–1.04; p= 0.036). Notably, more men received all four guideline-recommended drugs after STEMI (women 65.7% vs. men 69.8% after 90 days; p < 0.001). With increasing number of prescribed drugs, patients benefit even more. This concerned both sexes, but was more pronounced in men (with 4 prescribed drugs: women HR 0.52, 95%CI 0.50–0.55; men HR 0.48, 95% CI 0.47–0.50, p int = 0.014). In a contemporary nationwide analysis, women with STEMI were older, had more comorbidities, underwent revascularization less often and had an increased risk for major complications as well as overall survival. Guideline-recommended drug therapy was applied less frequently in women although associated with an improved overall-survival. [Display omitted] • Compared to men, women with STEMI were older and had more comorbidities. • Women had higher rates of inpatient complications, received percutaneous coronary intervention less often, and when adjusted for the risk profile, the female sex was associated with reduced overall survival. • After STEMI, women received all four guideline-recommended drugs less often, although the prognosis improved with the increase in these drugs. [ABSTRACT FROM AUTHOR]

RNA transcripts are not finished products. Like proteins undergo posttranslational modifications, RNAs undergo posttranscriptional modifications. Some of these modifications affect processing, stability or turnover of RNAs, others can 'edit' nucleotides, change the RNA's function and rewrite the genetic code. The body of RNA modifications is collectively called the 'epitranscriptome'. The epitranscriptome is dynamically regulated. This is the most clear for N6-methyladenosine (m6A), where both m6A-'writers' and –'erasers' have been identified and are also already being employed in studies on the effects of broad-scale m6A modifications on human disease, including cardiovascular disease. Even though not all modifications are readily reversible like m6A, most, if not all, other modifications are actively regulated in response to stressors, such as ischemia, starvation, or incubation with for example cytokines or oxidized LDL, all important factors in vascular remodelling and cardiovascular disease. Epitranscriptome research in human disease in general and in cardiovascular research is still in its infancy and methods to reliably detect and/or manipulate most RNA modifications are still lacking. Nonetheless, the number of studies on RNA modification and on writer-, eraser-, and reader-protein in various forms of vascular remodelling has increased dramatically over the last three years. This review aimed to discuss the available literature on the most common RNA modifications in different forms of vascular remodelling. Both adaptive vascular remodelling, including postischemic angiogenesis, as well as maladaptive remodelling, like atherosclerosis and aneurysm formation, and their direct consequences, such as myocardial infarction, acute stroke, peripheral artery disease and abdominal aorta aneurysm, have been discussed. [Display omitted] • The epitranscriptome, the collective of posttranscriptional modifications of RNAs, adds a layer of regulation of gene expression and function. • Over the past three years, epitranscriptome research in the cardiovascular field has started to take flight. • m6A and A-to-I editing dominate the epitranscriptome field in CVD, but other modifications are gaining momentum too. [ABSTRACT FROM AUTHOR]

• In real-world clinical practice, the initiation and up-titration of sacubitril/valsartan prescription remain challenging in patients with AMI. • Early use or high dosage of sacubitril/valsartan is associated with an improvement in primary composite endpoints as well as the incidence of new-onset HFrEF or HFpEF. • The low dose of sacubitril/valsartan is well tolerated and may be associated with similar outcomes compared with high dose in some circumstances (LVEF>50% or HF at baseline). In real-world clinical practice, the initiation and up-titration of sacubitril/valsartan remain challenging due to symptomatic hypotension in patients with acute myocardial infarction(AMI). The purpose of this study was to investigate the efficacy of different initial timing and dosage of sacubitril/valsartan in AMI patients. This prospective and observational cohort study enrolled AMI patients treated with percutaneous coronary intervention(PCI), and were categorized according to the initial timing and average daily doses of sacubitril/valsartan prescription. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, coronary revascularization, heart failure(HF) hospitalization and ischaemic stroke. Secondary outcomes included the new-onset HF, and the composite endpoints in AMI patients complicated with HF at baseline. The study population consisted of 915 AMI patients. After a median follow-up of 38 months, early use or high dosage of sacubitril/valsartan was associated with an improvement in primary endpoint as well as the incidence of new-onset HF. Early use of sacubitril/valsartan also ameliorated the primary endpoint in AMI patients with left ventricular ejection fraction(LVEF) ≤50% as well as LVEF>50%. Besides, early use of sacubitril/valsartan improved the clinical outcomes in AMI patients complicated with HF at baseline. The low dose was well tolerated and may be associated with similar outcomes compared with high dose under some circumstances(LVEF>50% or HF at baseline). Early use or high dosage of sacubitril/valsartan medication is associated with an improvement in clinical outcome. The low dose of sacubitril/valsartan is well tolerated and may be an acceptable alternative strategy. [ABSTRACT FROM AUTHOR]

When a catheter device is delivered during percutaneous coronary intervention, its passage can be disrupted by a deployed in a coronary artery. However, the condition and details of this phenomenon, that is impeded-by-stent phenomenon (ISP), remain unclear. We designed a prospective, open-label, single-center, observational study to clarify the incidence, predictors, and clinical impact of ISP in drug-eluting stents (DESs). Two independent operators observed and judged the occurrence of ISP, which was defined as all disturbances to a device delivery by deployed DESs. We consecutively used the Ultimaster™ (Terumo, Tokyo, Japan) DES for one month (109 patients, October 2018), followed by the Synergy™ (Boston Scientific Corporation, Marlborough, MA, USA) DES the next month (119 patients, November 2018). DESs (2.5–4.0 mm in diameter) were implanted in 230 de novo coronary vessels. ISPs were observed in 17 of 239 stented segments (7.1 %). Multivariate analysis showed that bifurcation lesions (adjusted odds ratio [OR], 4.2; 95 % confidence interval [CI], 1.5–12.6; p = 0.008), predilatation balloon diameter (mm) (OR, 0.2; 95 % CI, 0.1–0.9; p = 0.03), and Ultimaster™ use (OR, 6.0; 95 % CI, 1.9–27.2; p = 0.002) were independent predictors of ISPs. During the 1.5-year follow-up period, no repeat revascularization or stent thrombosis occurred in patients with ISP. ISP itself does not trigger notable clinical outcomes, including repeat revascularization and stent thrombosis. However, caution should be considered regarding the latent risk of procedural complications. • Impeded-by-stent phenomenon (ISP), a collision between a catheter device and a deployed stent, temporarily impedes device delivery during percutaneous coronary intervention. • The use of the Ultimaster stent, small pre-dilatation balloon, and bifurcation lesion were the independent predictors. • ISP does not bring complications, stent thromboses, and repeat revascularizations. [ABSTRACT FROM AUTHOR]

The use of eptifibatide combined with heparin during percutaneous coronary intervention (PCI) in patients presenting with ST-elevation myocardial infarction (STEMI) is recommended to be followed by continuous infusion. Recently, there are some suggestions that using bolus only may be sufficient and cost-effective but randomized trials are lacking. The goal of this study was to evaluate these two approaches in a double-blinded randomized control trial. The primary PCI patients who received bolus eptifibatide were randomized to 75 mg IV eptifibatide infusion or placebo blindly. The patients were followed up for the primary outcome of vascular or bleeding complications and secondary outcome of ischemic complications. 330 patients (165 from each group) completed the study. The mean age was 57.67 ± 11.53 years and 77.3 % were male. Major bleeding was seen in 1 patient in each group. Hematoma occurred in 8.5 %. The relative risk of hematoma and ecchymosis in bolus plus infusion group to bolus only group were 0.988 (95 % CI: 0.486–2.006) and 1.032 (95 % CI: 0.729–1.459). Multivariate analysis confirmed no significant differences in the bleeding event. Furthermore, there was no significant difference in in-hospital death or any ischemic events. (Cath lab death: 1.4 % in bolus only vs zero % in the control group, p = 0.217, stent thrombosis was seen in one patient in each group). There were no differences in the risk of access site ecchymosis, hematoma or major bleeding. Ischemic events and stent thrombosis rates were also similar. Our study suggests that using eptifibatide bolus only during PCI of patients with STEMI is safe and can be cost-saving. • Eptifibatide is commonly used in conjunction with heparin during high risk PCI with a recommended dose of initial weight based Bolus and at least 24 hours infusion • The goal of this study was to evaluate Bolus only arm in a double-blinded randomized control trial. • The primary PCI patients who received bolus eptifibatide were randomized to 75mg IV eptifibatide infusion (short-term protocol = group A) or placebo (group B) blindly. • There was no differences in the risk of access site ecchymosis, hematoma or major bleeding. Ischemic events and stent thrombosis rates were also similar. • Our study suggests that using eptifibatide bolus only during PCI of patients with STEMI is safe and can be cost saving. [ABSTRACT FROM AUTHOR]

Intracoronary pressure wire is useful to guide revascularization in patients with coronary artery disease. To evaluate changes in diagnosis (coronary artery disease extent), treatment strategy and clinical results after intracoronary pressure wire study in real-life patients with intermediate coronary artery stenosis. Observational, prospective and multicenter registry of patients in whom pressure wire was performed. The extent of coronary artery disease and the treatment strategy based on clinical and angiographic criteria were recorded before and after intracoronary pressure wire guidance. 12-month incidence of MACE (cardiovascular death, non-fatal myocardial infarction or new revascularization of the target lesion) was assessed. 1414 patients with 1781 lesions were included. Complications related to the procedure were reported in 42 patients (3.0 %). The extent of coronary artery disease changed in 771 patients (54.5 %). There was a change in treatment strategy in 779 patients (55.1 %) (18.0 % if medical treatment; 68.8 % if PCI; 58.9 % if surgery (p < 0.001 for PCI vs medical treatment; p = 0.041 for PCI vs CABG; p < 0.001 for medical treatment vs CABG)). In patients with PCI as the initial strategy, the change in strategy was associated with a lower rate of MACE (4.6 % vs 8.2 %, p = 0.034). The use of intracoronary pressure wire was safe and led to the reclassification of the extent of coronary disease and change in the treatment strategy in more than half of the cases, especially in patients with PCI as initial treatment. • In a non-controlled, real-life setting, the pressure wire is safe, with an extremely low complications rate. • Following pressure wire use, we have demonstrated a very significant change in assessment of the extent of coronary disease. • Following pressure wire use, we have evidenced a very significant change not only in treatment modality (medical, PCI or CABG) but also in management strategy. • We have shown that the change in treatment modality and/or strategy has prognostic implications, particularly in those patients in which the initial intention was to perform PCI. • These results are different from those observed in previous studies conducted in populations with very limited representation of patients with ACS and in reimbursement-based healthcare systems. [ABSTRACT FROM AUTHOR]

Backgound Aims: This meta-analysis aims at summarizing the whole body of research on cell therapies for acute myocardial infarction (MI) in the mouse model to bring forward ongoing research in this field of regenerative medicine. Despite rather modest effects in clinical trials, pre-clinical studies continue to report beneficial effects of cardiac cell therapies for cardiac repair following acute ischemic injury. Results: The authors' meta-analysis of data from 166 mouse studies comprising 257 experimental groups demonstrated a significant improvement in left ventricular ejection fraction of 10.21% after cell therapy compared with control animals. Subgroup analysis indicated that second-generation cell therapies such as cardiac progenitor cells and pluripotent stem cell derivatives had the highest therapeutic potential for minimizing myocardial damage post-MI. Conclusions: Whereas the vision of functional tissue replacement has been replaced by the concept of regional scar modulation in most of the investigated studies, rather basic methods for assessing cardiac function were most frequently used. Hence, future studies will highly benefit from integrating methods for assessment of regional wall properties to evolve a deeper understanding of how to modulate cardiac healing after acute MI. The graphical abstract was created with BioRender.com. [Display omitted] [ABSTRACT FROM AUTHOR]

Cardiovascular health level according to the American Heart Association's Life's Essential 8 (LE8) in China and its effectiveness on the 10-year and lifetime risk of atherosclerotic cardiovascular diseases is unclear. This prospective study included 88,665 participants in the China-PAR cohort (data from 1998 to 2020) and 88,995 in the Kailuan cohort (data from 2006 to 2019). Analyses were conducted by November 2022. LE8 was measured according to the American Heart Association's LE8 algorithm, and a high cardiovascular health status was defined as a LE8 score ≥80 points. Participants were followed for the primary composite outcomes, including fatal and nonfatal acute myocardial infarction, ischemic stroke, and hemorrhagic stroke. The lifetime risk was estimated from the cumulative risk of atherosclerotic cardiovascular diseases through ages 20−85 years, the association of LE8 and LE8 change with atherosclerotic cardiovascular diseases was assessed with the Cox proportional-hazards model, and partial population-attributable risks evaluated the proportion of atherosclerotic cardiovascular diseases that could be averted. The mean LE8 score was 70.0 in the China-PAR cohort and 64.6 in the Kailuan cohort, with 23.3% and 8.0% of participants having a high cardiovascular health status, respectively. Participants in the highest quintile had about 60% lower 10-year and lifetime risk of atherosclerotic cardiovascular diseases in the China-PAR and Kailuan cohorts than participants with the lowest quintile LE8 score. If everyone maintained the highest quintile of LE8 score, approximately half of the atherosclerotic cardiovascular diseases could be prevented. The participant with LE8 score that increased from the lowest to the highest tertile during 2006−2012 had a 44% (hazard ratio=0.56; 95% CI=0.45, 0.69) lower observed risk and a 43% (hazard ratio=0.57; 95% CI=0.46, 0.70) lower lifetime risk of atherosclerotic cardiovascular diseases than those remaining in the lowest tertile in the Kailuan cohort. The LE8 score was below optimal levels in Chinese adults. A high baseline LE8 score and an improving LE8 score were associated with decreased 10-year and lifetime risk of atherosclerotic cardiovascular diseases. [ABSTRACT FROM AUTHOR]

We aimed to analyze the impact of timing of implantation (strategy-outcome relationship) and volume of procedures (volume-outcome relationship) on survival of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for cardiogenic shock complicating acute myocardial infarction (AMI). We conducted an observational retrospective study through two propensity score-based analyses using a nationwide database between January 2013 and December 2019. We classified patients into early implantation (VA ECMO on the day of primary percutaneous coronary intervention [PCI]) and delayed implantation (VA ECMO beyond the day of PCI) groups. We classified patients into low- or high-volume groups based on the median hospital volume. During the study period 649 VA ECMO were implanted across 20 French hospitals. Mean age was 57.1 ± 10.4 years, 80% were male. Overall, 90-day mortality was 64.3%. Patients in the early implantation group (n = 479, 73.8%) did not show a statistical difference in 90-day mortality than in the delayed group (n = 170, 26.2%) (HR: 1.18; 95% CI 0.94–1.48; p = 0.153). The mean number of VA ECMO implanted during the study period by low-volume centers was 21.3 ± 5.4 as compared to 43.6 ± 11.8 in high-volume centers. There was no significant difference in 90-day mortality between high-volume and low-volume centers (HR: 1.00; 95% CI: 0.82–1.23; p = 0.995). In this real-world nationwide study, we did not find a significant association between early VA ECMO implantation as well as high-volume centers and lower mortality in AMI-related refractory cardiogenic shock. [Display omitted] • 90-day mortality in AMI complicated by cardiogenic shock requiring VA ECMO was 64%. • Early VA ECMO implantation did not show a survival advantage in 90-day mortality. • VA ECMO implantation at high-volume centers did not show a survival advantage. [ABSTRACT FROM AUTHOR]

Approximately half of the patients presenting with ST-segment elevation myocardial infarction have also significant atherosclerotic disease affecting coronary segments other than the infarct-related artery. Optimal management of residual lesions in this clinical setting has been a topic of intense research in the last decade. On the one hand, a large body of evidence has consistently shown the benefit of complete revascularization for the reduction of adverse cardiovascular outcomes. On the other hand, some crucial aspects such as the optimal timing or the best strategy of the complete treatment approach remain a matter of controversy. In this review, we aim to provide a thorough critical appraisal of the available literature regarding this topic, by discussing areas of relative certainty, gaps in the knowledge, approach to specific clinical subsets and future research directions. • Complete revascularization of STEMI and multivessel disease is beneficial. • Best timing of complete revascularization is uncertain. • Optimal strategy for non-culprit lesions selection is controversial. [ABSTRACT FROM AUTHOR]