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Background: Although some studies have investigated sex-related outcomes up to 5 years after percutaneous coronary intervention (PCI), analyses at longer follow-up (ie, to 10 years) in large cohorts treated exclusively with drug-eluting stent (DES) platforms are lacking. Therefore, this study aimed to define whether sex-related differences in long-term outcomes after PCI persist both in the DES era and at longer-term follow-up. Methods: Individual data of patients treated with DES in 5 randomized controlled trials with 10-year follow-up were pooled. Patients were divided into 2 groups by sex. The analysis of individual participant data was performed using a 1-stage approach by entering a clustering effect by parent study in all univariable and multivariable models focusing on sex. The main outcomes of interest for this analysis included cardiovascular death, myocardial infarction, repeat revascularization, and definite stent thrombosis to 10 years after PCI. Survival was analyzed by the Kaplan-Meier method to estimate the time to first event, and differences between the 2 groups were tested with the log-rank test. Hazard ratios (HRs) and 95% CIs were calculated with a Cox proportional hazards model. Conventional multivariable analyses with adjustment for relevant variables were performed. Results: Among 9700 patients undergoing PCI with DES implantation included in the present analysis, 2296 were women and 7404 were men. Through to 10 years, cardiovascular death occurred in 407 of the 2296 female patients and 1012 of the 7404 male patients (adjusted HR [HR adj ], 0.94 [95% CI, 0.80–1.11]). Female sex was associated with a lower risk of repeat revascularization of the target lesion (HR adj , 0.80 [95% CI, 0.74–0.87]), target vessel (HR adj , 0.81 [95% CI, 0.76–0.87]), and nontarget vessels (HR adj , 0.69 [95% CI, 0.62–0.77]). Compared with male patients, female patients displayed an increased risk of myocardial infarction in the first 30 days after PCI with DES (HR adj , 1.65 [95% CI, 1.24–2.19]) but a comparable risk of myocardial infarction thereafter. The risk of definite stent thrombosis was not significantly different between female and male patients (HR adj , 1.14 [95% CI, 0.89–1.47]). Conclusions: Through to 10-year follow-up after PCI with DES, female patients are at increased risk of early myocardial infarction, receive fewer repeat revascularizations, and have no difference in cardiovascular mortality compared with male patients.

Many patients with coronary artery disease (CAD) have reduced the effect of aspirin, which may partly be explained by immature platelets. We aimed to investigate whether immature platelet markers can predict cardiovascular events in a large cohort of stable CAD patients. A total of 900 stable CAD patients were included and followed for a median of 3 years. We measured markers of immature platelets (platelet count, immature platelet count, immature platelet fraction, mean platelet volume, platelet distribution width, platelet mass, and thrombopoietin) using automated flow cytometry and studied their relation to cardiovascular events. Our primary endpoint was a composite of acute myocardial infarction (MI), ischemic stroke, and cardiovascular death. A composite of MI, ischemic stroke, stent thrombosis and all-cause mortality was analyzed as a secondary endpoint. We found no difference in immature platelet markers between CAD patients with or without cardiovascular events. Regression analysis using hazards rates showed that markers of immature platelets did not have any predictive value for endpoints (p-values >.05). Markers of immature platelets did not predict future cardiovascular events during a 3-year follow-up period in CAD patients. This suggests that immature platelets measured in a stable phase does not have a major role in predicting future cardiovascular events.

Aims To assess differences in long-term outcome and functional status of patients with cardiogenic shock (CS) treated by percutaneous mechanical circulatory support (pMCS) and intra-aortic balloon pump (IABP). Methods and results Long-term follow-up of the multicentre, randomized IMPRESS in Severe Shock trial (NTR3450) was performed 5-year after initial randomization. Between 2012 and 2015, a total of 48 patients with severe CS from acute myocardial infarction (AMI) with ST-segment elevation undergoing immediate revascularization were randomized to pMCS by Impella CP (n = 24) or IABP (n = 24). For the 5-year assessment, all-cause mortality, functional status, and occurrence of major adverse cardiac and cerebrovascular event (MACCE) were assessed. MACCE consisted of death, myocardial re-infarction, repeat percutaneous coronary intervention, coronary artery bypass grafting, and stroke. Five-year mortality was 50% (n = 12/24) in pMCS patients and 63% (n = 15/24) in IABP patients (relative risk 0.87, 95% confidence interval 0.47–1.59, P = 0.65). MACCE occurred in 12/24 (50%) of the pMCS patients vs. 19/24 (79%) of the IABP patients (P = 0.07). All survivors except for one were in New York Heart Association Class I/II [pMCS n = 10 (91%) and IABP n = 7 (100%), P = 1.00] and none of the patients had residual angina. There were no differences in left ventricular ejection fraction between the groups (pMCS 52 ± 11% vs. IABP 48 ± 10%, P = 0.53). Conclusions In this explorative randomized trial of patients with severe CS after AMI, there was no difference in long-term 5-year mortality between pMCS and IABP-treated patients, supporting previously published short-term data and in accordance with other long-term CS trials., Graphical Abstract

BACKGROUND: Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI.METHODS: A total of 2,571 participants were prospectively enrolled in the Influenza vaccination after myocardial infarction (IAMI) trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in eight countries from October 1, 2016 to March 1, 2020. Here we report vaccine effectiveness in the 2,467 participants with ST-segment elevation MI (STEMI, n = 1,348) or non-ST-segment elevation MI (NSTEMI, n = 1,119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification.RESULTS: Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P = .237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at one year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P = .028).CONCLUSIONS: The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI.

ImportancePatients with stroke due to nontraumatic (spontaneous) intracerebral hemorrhage (ICH) often harbor vascular risk factors and comorbidities, but it is unclear which major adverse cardiovascular events (MACEs) occur more frequently among patients with a prior ICH than the general population.ObjectiveTo evaluate the risk of a MACE for patients with a prior ICH compared with the general population.Design, Setting, and ParticipantsThis cohort study identified 8991 patients with a first ICH in the Danish Stroke Registry from January 1, 2005, to June 30, 2018, who were aged 45 years or older and survived more than 30 days after an ICH. Patients in this ICH cohort were matched 1:40 on age, sex, and ICH-onset date with a comparison cohort of 359 185 individuals from the general population without a prior ICH. Both cohorts were followed up for 6 months or more until December 31, 2018, for outcomes using registry data. Data were analyzed from October 1, 2021, to July 19, 2022.ExposuresIntracerebral hemorrhage identified by a nationwide clinical database.Main Outcomes and MeasuresThe main outcomes were ICH, ischemic stroke, myocardial infarction, and a composite of MACEs. For each outcome, a case-control study nested within the cohorts was also performed, adjusting for time-varying exposures and potential confounders. Crude absolute event rates per 100 person-years, adjusted hazard ratios (aHRs) and 95% CIs and, in the nested case-control analyses, crude and adjusted odds ratios and 95% CIs were calculated.ResultsThe ICH cohort (n = 8991; 4814 men [53.5%]; mean [SD] age, 70.7 [11.5] years) had higher event rates than the comparison cohort (n = 359 185; 192 256 men [53.5%]; mean [SD] age, 70.7 [11.5] years) for MACEs (4.16 [95% CI, 3.96-4.37] per 100 person-years vs 1.35 [95% CI, 1.33-1.36] per 100 person-years; aHR, 3.13 [95% CI, 2.97-3.30]), ischemic stroke (1.52 [95% CI, 1.40-1.65] per 100 person-years vs 0.56 [95% CI, 0.55-0.57] per 100 person-years; aHR, 2.64 [95% CI, 2.43-2.88]), and ICH (1.44 [95% CI, 1.32-1.56] per 100 person-years vs 0.06 [95% CI, 0.06-0.07] per 100 person-years; aHR, 23.49 [95% CI, 21.12-26.13]) but not myocardial infarction (0.52 [95% CI, 0.45-0.60] per 100 person-years vs 0.48 [95% CI, 0.47-0.49] per 100 person-years; aHR, 1.12 [95% CI, 0.97-1.29]). Nested case-control analyses returned risk estimates of similar magnitude as the cohort analyses.Conclusions and RelevanceThe findings of this cohort study suggest that Danish patients with a prior ICH had statistically significantly higher rates of MACEs than the general population, indicating a need for attention to optimal secondary prevention with blood pressure lowering and antithrombotic and statin therapies after an ICH in clinical research and practice.

INTRODUCTION: Despite advances in treatment of patients with cardiogenic shock following acute myocardial infarction (AMICS) in-hospital mortality remains around 50%. Outcome varies among patient subsets and the elderly often have a poor a priori prognosis. We sought to investigate outcome among elderly AMICS patients referred to evaluation and treatment at a tertiary university hospital. METHODS: Current analysis was based on the RETROSHOCK registry comprising consecutive AMICS patients admitted to tertiary care. Patients in the registry were individually identified and validated. RESULTS: Of 1,716 admitted patients, 496 (28.9%) patients were ≥75 years old. Older patients were less likely to be admitted directly to a tertiary centre (59.4% vs. 69.9%, P = 0.003), receive mechanical support devices (i.e., Impella® (8.9% vs. 15.0%, P = 0.003), and undergo revascularization attempt (76.8% vs. 90.2%, P

Aims The post-discharge outcomes of patients with cancer who undergo PCI are not well understood. This study evaluates the rates of readmissions within 90 days for acute myocardial infarction (AMI) and bleeding among patients with cancer who undergo percutaneous coronary intervention (PCI). Methods and results Patients treated with PCI in the years from 2010 to 2014 in the US Nationwide Readmission Database were evaluated for the influence of cancer on 90-day readmissions for AMI and bleeding. A total of 1 933 324 patients were included in the analysis (2.7% active cancer, 6.8% previous history of cancer). The 90-day readmission for AMI after PCI was higher in patients with active cancer (12.1% in lung, 10.8% in colon, 7.5% in breast, 7.0% in prostate, and 9.1% for all cancers) compared to 5.6% among patients with no cancer. The 90-day readmission for bleeding after PCI was higher in patients with active cancer (4.2% in colon, 1.5% in lung, 1.4% in prostate, 0.6% in breast, and 1.6% in all cancer) compared to 0.6% among patients with no cancer. The average time to AMI readmission ranged from 26.7 days for lung cancer to 30.5 days in colon cancer, while the average time to bleeding readmission had a higher range from 38.2 days in colon cancer to 42.7 days in breast cancer. Conclusions Following PCI, patients with cancer have increased risk for readmissions for AMI or bleeding, with the magnitude of risk depending on both cancer type and the presence of metastasis.

Aim Activated blood platelet products facilitate myocardial intracellular Ca2+ overload, thereby provoking afterdepolarizations and increasing susceptibility of ischemic myocardium to ventricular fibrillation (VF). These effects are counteracted in vitro by acetylsalicylic acid (ASA), but no prior study investigated whether ASA is associated with decreased out-of-hospital cardiac arrest (OHCA) risk on a population level. Therefore, we studied whether ASA and other antiplatelet drugs (carbasalate calcium, clopidogrel) are associated with decreased risk of OHCA. Methods We conducted a population-based case-control study among individuals (772 OHCA-cases with documented VT/VF, 2444 non-OHCA-controls) who had used antiplatelet drugs in the year before index-date (OHCA-date), and studied the association between current antiplatelet drug use and OHCA-risk with multivariable logistic regression analysis. Results ASA use was associated with reduced OHCA-risk (adjusted odds ratio (ORadj) 0.6 [0.5–0.8]), and more so in women (ORadj 0.3 [0.2–0.6]) than in men (ORadj 0.7 [0.5–0.95], Pinteraction 0.021). Carbasalate calcium was associated with decreased OHCA-risk in women (ORadj 0.5 [0.3–0.9]), but not in men (ORadj 1.3 [0.96–1.7], Pinteraction 0.005). Clopidogrel was not associated with reduction in OHCA-risk. Risk reduction associated with ASA in patients with OHCA was similar in the presence of acute myocardial infarction (AMI) (ORadj 0.6 [0.4–0.9]) and in the absence of AMI (ORadj 0.7 [0.4–1.2]). Conclusion ASA use was associated with reduced OHCA-risk in both sexes, and more so in women, while carbasalate calcium only protected women. Clopidogrel was not associated with reduced OHCA-risk.

Background Physical and mental well-being after critical illness may be objectified by the ability to work. We examined return to work among patients with myocardial infarction (MI) by cardiogenic shock (CS) status. Methods Danish nationwide registries were used to identify patients with first-time MI by CS status between 2005 and 2015, aged 18–63 years, working before hospitalization and discharged alive. Multiple logistic regression models were used to compare groups. Results We identified 19 799 patients with MI of whom 653 had CS (3%). The median age was similar for patients with and without CS (53 years, interquartile range 47–58). One-year outcomes in patients with and without CS were as follows: 52% vs. 83% returned to work, 41% vs. 16% did not and 6% vs. 1% died. The adjusted odds ratio (OR) of returning to work was 0.53 [95% confidence limit (CI): 0.42–0.66]. In patients with CS, males and patients surviving OHCA were more likely to return to work (OR: 1.83, 95% CI: 1.15–2.92 and 1.55, 95% CI: 1.00–2.40, respectively), whereas prolonged hospitalization (OR: 0.38, 95% CI: 0.22–0.65) and anoxic brain damage (OR: 0.36, 95% CI: 0.18–0.72) were associated with lower likelihood of returning to work. Conclusion In patients with MI discharged alive, approximately 80% of those without CS returned to work at 1-year follow-up in contrast to 50% of those with CS. Among patients with CS, male sex and OHCA survivors were markers positively related to return to work, whereas prolonged hospitalization and anoxic brain damage were negatively related markers.

Background Hyperoxia and oxidative stress may be associated with increased risk of myocardial injury. The authors hypothesized that a perioperative inspiratory oxygen fraction of 0.80 versus 0.30 would increase the degree of myocardial injury within the first 3 days of surgery, and that an antioxidant intervention would reduce degree of myocardial injury versus placebo. Methods A 2 × 2 factorial, randomized, blinded, multicenter trial enrolled patients older than 45 yr who had cardiovascular risk factors undergoing major noncardiac surgery. Factorial randomization allocated patients to one of two oxygen interventions from intubation and at 2 h after surgery, as well as antioxidant intervention or matching placebo. Antioxidants were 3 g IV vitamin C and 100 mg/kg N-acetylcysteine. The primary outcome was the degree of myocardial injury assessed by the area under the curve for high-sensitive troponin within the first 3 postoperative days. Results The authors randomized 600 participants from April 2018 to January 2020 and analyzed 576 patients for the primary outcome. Baseline and intraoperative characteristics did not differ between groups. The primary outcome was 35 ng · day/l (19 to 58) in the 80% oxygen group; 35 ng · day/l (17 to 56) in the 30% oxygen group; 35 ng · day/l (19 to 54) in the antioxidants group; and 33 ng · day/l (18 to 57) in the placebo group. The median difference between oxygen groups was 1.5 ng · day/l (95% CI, −2.5 to 5.3; P = 0.202) and −0.5 ng · day/l (95% CI, −4.5 to 3.0; P = 0.228) between antioxidant groups. Mortality at 30 days occurred in 9 of 576 patients (1.6%; odds ratio, 2.01 [95% CI, 0.50 to 8.1]; P = 0.329 for the 80% vs. 30% oxygen groups; and odds ratio, 0.79 [95% CI, 0.214 to 2.99]; P = 0.732 for the antioxidants vs. placebo groups). Conclusions Perioperative interventions with high inspiratory oxygen fraction and antioxidants did not change the degree of myocardial injury within the first 3 days of surgery. This implies safety with 80% oxygen and no cardiovascular benefits of vitamin C and N-acetylcysteine in major noncardiac surgery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background: Cardiogenic shock (CS) is a critical complication to acute myocardial infarction (AMI), with short-term mortality rates exceeding 40%. However, no international consensus of a CS definition exists. This may compromise interstudy comparability. Aims: The aim of the current study was to review differences and similarities of CS enrolment criteria in AMI-related CS randomized clinical trials (RCT). Methods: From the electronic databases MEDLINE and EMBASE we identified all AMI-related CS trials. Results: A total of 19 trials comprising a total of 2674 unique patients with CS were identified. Seven trials investigated left ventricular assist devices, eight investigated medical treatments, three percutaneous coronary intervention (PCI), and one trial investigated targeted temperature management. The inclusion criteria, baseline hemodynamics, endpoints, and mortality varied markedly between trials. Hypotension was the most frequent overall inclusion criterion (17 [90%] trials), and a systolic blood pressure

BACKGROUND: Many patients with heart failure (HF) are treated with warfarin or non-vitamin K oral anticoagulants (NOACs). Randomized outcome-driven comparisons of different anticoagulant strategies in HF are lacking. Data from international, government-mandated registries may be useful in understanding the real-life use of various anticoagulants and how they are linked to outcomes.STUDY QUESTION: To assess 2015 annual all-cause mortality, myocardial infarction, and stroke rates co-reported for warfarin and NOACs in subjects with and without HF in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.STUDY DESIGN: We extracted and examined outcome cases in subjects with HF and on warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban and stratified these according to anticoagulants.MEASURES AND OUTCOMES: Annual all-cause mortality, myocardial infarction, and stroke in FAERS.ANALYSIS METHOD: Odds ratio (OR) and χ(Equation is included in full-text article.)for oral anticoagulants from FAERS with and without HF among complete primary reports issued in 2015.RESULTS: FAERS reported 137,026 HF cases, with death co-reported in 42,942 (31.3%). In total, 11,278 (8.2%) HF patients were treated with anticoagulants, with more prescribed warfarin (n = 8260) than all NOACs combined (n = 3018). Very few reports for edoxaban were available. Warfarin consistently displayed a signal for excess adverse events compared to NOACs: OR (95% confidence interval) for the composite of mortality, myocardial infarction, and stroke were 1.91 (1.76-2.07) versus apixaban, 1.92 (1.81-2.03) versus dabigatran, 4.09 (3.38-4.37) versus rivaroxaban, and 2.64 (2.53-2.76) versus all NOACs combined (all P < 0.001). Warfarin, compared to all NOACs combined, demonstrated higher rates of all-cause mortality [OR = 2.69 (95% confidence interval, 2.49-2.90)], myocardial infarction [5.30 (4.17-6.74)], stroke [OR = 8.85 (6.61-11.84)], and ischemic stroke [OR = 12.73 (8.87-18.27); all P < 0.001].CONCLUSIONS: Annual 2015 FAERS profiles in HF patients reveal that warfarin was numerically dominant. Warfarin was associated with higher risk of death, myocardial infarction, and stroke compared to NOACs. These observational data provide real-world insight into a potential safety benefit of NOACs over warfarin in the setting of HF.

Background Concomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP). Objective To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP. Methods CS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 μg/kg/min), epinephrine (0.10 μg/kg/min), or dopamine (10 μg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 μg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO2), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression. Results All catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 103 (mmHg × mL)/min [95% CI (174.1, 509.5), p 2 significantly improved during all catecholamines. Phenylephrine, a vasoconstrictor, caused a significant increase in cardiac work by 437.8 × 103 (mmHg × mL)/min [95% CI (297.9, 577.6), p p = 0.001), but no significant change in LV stroke work. Also, phenylephrine tended to decrease SvO2 (p = 0.063) and increased arterial lactate levels (p = 0.002). Conclusion Catecholamines increased end-organ perfusion at the expense of increased cardiac work, most by dopamine. However, phenylephrine increased cardiac work with no increase in end-organ perfusion.

The multinational, observational CVD-REAL study recently showed that initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with significantly lower rates of death and heart failure vs other glucose-lowering drugs (oGLDs). This sub-analysis of the CVD-REAL study sought to determine the association between initiation of SGLT-2i vs oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the USA, Sweden, Norway and Denmark were used to identify patients with T2D who newly initiated treatment with SGLT-2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs. A non-parsimonious propensity score was developed within each country to predict initiation of SGLT-2i, and patients were matched 1:1 in the treatment groups. Pooled hazard ratios (HRs) and 95% CIs were generated using Cox regression models. Overall, 205 160 patients were included. In the intent-to-treat analysis, over 188 551 and 188 678 person-years of follow-up (MI and stroke, respectively), there were 1077 MI and 968 stroke events. Initiation of SGLT-2i vs oGLD was associated with a modestly lower risk of MI and stroke (MI: HR, 0.85; 95%CI, 0.72-1.00; P =.05; Stroke: HR, 0.83; 95% CI, 0.71-0.97; P =.02). These findings complement the results of the cardiovascular outcomes trials, and offer additional reassurance with regard to the cardiovascular effects of SGLT-2i, specifically as it relates to ischaemic events.

Introduction Mechanical complications after myocardial infarction (MI) have become uncommon since the introduction of primary angioplasty. They can lead to a rapid clinical deterioration and a fatal outcome, with patient’s survival being depen­dent on their prompt recognition and intervention. We describe a case of two rare mechanical complications: a partial papillary muscle rupture after MI, followed by an early severe obstructive thrombosis of the implanted bioprosthetic valve. […] Partial Papillary Muscle Rupture after Myocardial Infarction and Early Severe Obstructive Bioprosthetic [...]

Introducao O pseudoaneurisma (PA) do ventriculo esquerdo (VE) constitui uma complicacao mecânica rara do infarto agudo do miocardio (IAM). Resulta de ruptura miocardica, em que o processo hemorragico e contido pelo pericardio aderente. Ocorre mais comumente na parede ventricular inferior e posterior, uma vez que a ruptura da parede anterior do ventriculo conduz habitualmente ao tamponamento cardiaco e morte imediata, enquanto que a face infero-posterior do coracao se apoia sobre o diafragma, facilitando a contencao da cavidade ventricular pelo pericardio. [...]

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden. The ERIC-PPCI trial was funded by a British Heart Foundation clinical study grant (grant number CS/14/3/31002) and a University College London Hospitals/University College London Biomedical Research Centre clinical research grant. The CONDI-2 trial was funded by Danish Innovation Foundation grants (grant numbers 11-108354 and 11-115818), Novo Nordisk Foundation (grant number NNF13OC0007447), and TrygFonden (grant number 109624). DJH was supported by the British Heart Foundation (grant number FS/10/039/28270), the National Institute for Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the Duke-National University Singapore Medical School, the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (grant number NMRC/CSA-SI/0011/2017) and its Collaborative Centre Grant scheme (grant number NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (grant number MOE2016-T2-2-021). HEB was supported by the Novo Nordisk Foundation (grant numbers NNF14OC0013337, NNF15OC0016674). RKK is supported by the Oxford NIHR Biomedical Centre. The research was also supported by the NIHR infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health. This article is based on the work of COST Action EU-CARDIOPROTECTION (CA16225) and supported by COST (European Cooperation in Science and Technology). We thank all study personnel for their invaluable assistance. Sí

Backgrund: New-onset atrial fibrillation complicating acute myocardial infarction represents an important challenge, with prognostic significance. Objective: To study the incidence, impact on therapy and mortality, and to identify predictors of development of new-onset atrial fibrillation during hospital stay for ST-segment elevation myocardial infarction. Methods: We studied all patients with ST-elevation myocardial infarction included consecutively, between 2010 and 2017, in a Portuguese national registry and compared two groups: 1 - no atrial fibrillation and 2 - new-onset atrial fibrillation. We adjusted a logistic regression model data analysis to assess the impact of new-onset atrial fibrillation on in-hospital mortality and to identify independent predictors of its development. A p value < 0.05 was considered significant. Results: We studied 6325 patients, and new-onset atrial fibrillation was found in 365 (5.8%). Reperfusion was successfully accomplished in both groups with no difference regarding type of reperfusion. In group 2, therapy with beta-blockers and angiotensin-conversion enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) was less frequent, 20.6% received anticoagulation at discharge and 16.1% were on triple therapy. New-onset atrial fibrillation was associated with more in-hospital complications and mortality. However, it was not found as an independent predictor of in-hospital mortality. We identified age, prior stroke, inferior myocardial infarction and complete atrioventricular block as independent predictors of new-onset atrial fibrillation. Conclusion: New-onset atrial fibrillation remains a frequent complication of myocardial infarction and is associated with higher rate of complications and in-hospital mortality. Age, prior stroke, inferior myocardial infarction and complete atrioventricular block were independent predictors of new onset atrial fibrillation. Only 36.7% of the patients received anticoagulation at discharge. Resumo Fundamento: A fibrilação auricular de novo no contexto de infarto agudo do miocárdio representa um importante desafio com potencial impacto prognóstico. Objetivo: Determinar a incidência, impacto na terapêutica e mortalidade, e identificar possíveis preditores do aparecimento de fibrilação auricular de novo durante o internamento por infarto agudo do miocárdio com supradesnivelamento do segmento ST. Métodos: Estudamos todos os pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST inseridos consecutivamente de 2010 a 2017 num registro nacional português e comparamos dois grupos: 1 - sem fibrilação auricular; 2- com fibrilação auricular de novo. Efetuamos análise com modelo de regressão logística para avaliar o impacto de fibrilação auricular de novo na mortalidade intra-hospitalar e identificar preditores independentes para o seu aparecimento. Para teste de hipóteses, considerou-se significativo p < 0,05. Resultados: Estudamos 6325 pacientes, dos quais 365 (5.8%) apresentaram fibrilação auricular de novo. Não houve diferença no número de pacientes reperfundidos nem na estratégia de reperfusão. No grupo 2, terapêutica com betabloqueadores e IECA/ARA foi menos frequente, 20.6% tiveram alta sob anticoagulação oral e 16.1% sob terapêutica tripla. A fibrilação auricular de novo associou-se a maior incidência de complicações e mortalidade intra-hospitalar, mas não foi preditor independente de mortalidade intra-hospitalar. Identificamos idade, acidente vascular cerebral prévio, infarto inferior e bloqueio auriculoventricular completo como preditores independentes de fibrilação auricular de novo. Conclusões: A fibrilação auricular de novo continua sendo uma complicação frequente do infarto agudo do miocárdio, estando associada a aumento das complicações e mortalidade intra-hospitalar. Apenas 36.7% desses pacientes teve alta sob anticoagulação.

Aims: Mortality in cardiogenic shock patients remains high. Short-term mechanical circulatory support with Impella can be used to support the circulation in these patients, but data from randomised controlled studies and ‘real-world’ data are sparse. The aim is to describe real-life data on outcomes and complications of our 12 years of clinical experience with Impella in patients with cardiogenic shock after acute myocardial infarction and to identify predictors of 6-month mortality. Methods: We describe a single-centre registry from October 2004 to December 2016 including all patients treated with Impella for cardiogenic shock after acute myocardial infarction. We report outcomes and complications and identify predictors of 6-month mortality. Results: Our overall clinical experience consists of 250 patients treated with Impella 2.5, Impella CP or Impella 5.0. A total of 172 patients received Impella therapy for cardiogenic shock, of which 112 patients had cardiogenic shock after acute myocardial infarction. The mean age was 60.1±10.6 years, mean arterial pressure was 67 (56–77) mmHg, lactate was 6.2 (3.6–9.7) mmol/L, 87.5% were mechanically ventilated and 59.6% had a cardiac arrest before Impella placement. Overall 30-day mortality was 56.2% and 6-month mortality was 60.7%. Complications consisted of device-related vascular complications (17.0%), non-device-related bleeding (12.5%), haemolysis (7.1%) and stroke (3.6%). In a multivariate analysis, pH before Impella placement is a predictor of 6-month mortality. Conclusions: Our registry shows that Impella treatment in cardiogenic shock after acute myocardial infarction is feasible, although mortality rates remain high and complications occur.

Background Chemotherapy-related coronary artery disease (CAD) is becoming an emerging issue in clinic. However, the underlying mechanism of chemotherapy-related CAD remains unclear. Objective The study investigated the association between chemotherapy and atherosclerotic anatomical abnormalities of coronary arteries among lung cancer patients. Methods Patients undergoing coronary angiography (CAG) between 2010 and 2017, who previously had lung cancer, were examined. Risk factors associated with CAD and information about lung cancer were evaluated. We assessed coronary-artery abnormalities by SYNTAX score (SXscore) based on CAG. In logistic-regression analysis, we defined high SXscore (SXhigh) grade as positive if ≥22. Data were analyzed through descriptive statistics and regression analysis. Results A total of 94 patients were included in the study. The SXscore was higher in the chemotherapy group than in the non-chemotherapy group (25.25, IQR [4.50-30.00] vs. 16.50, IQR [ 5.00-22.00], p = 0.0195). The SXhigh rate was greater in the chemotherapy group than in the non-chemotherapy group (58.33% vs. 25.86; p = 0.0016). Both univariate (OR:4.013; 95% CI:1.655-9.731) and multivariate (OR:5.868; 95% CI:1.778-19.367) logistic-regression analysis revealed that chemotherapy increased the risk of greater SXhigh rates. Multivariate stepwise logistic-regression analysis showed the risk of more severe anatomical CAD is increased by chemotherapy as a whole by 5.323 times (95% CI: 2.002-14.152), and by platinum-based regimens by 5.850 times (95% CI: 2.027-16.879). Conclusions Chemotherapy is associated with anatomical complexity and severity of CAD, which might partly account for the higher risk of chemotherapy-related CAD among lung cancer patients. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Aims Myocardial infarction (MI) leads to an enhanced release of endocannabinoids and a massive accumulation of neutrophils and monocytes within the ischaemic myocardium. These myeloid cells originate from haematopoietic precursors in the bone marrow and are rapidly mobilized in response to MI. We aimed to determine whether endocannabinoid signalling is involved in myeloid cell mobilization and cardiac recruitment after ischaemia onset. Methods and results Intravenous administration of endocannabinoid 2-arachidonoylglycerol (2-AG) into wild type (WT) C57BL6 mice induced a rapid increase of blood neutrophil and monocyte counts as measured by flow cytometry. This effect was blunted when using cannabinoid receptor 2 knockout mice. In response to MI induced in WT mice, the lipidomic analysis revealed significantly elevated plasma and cardiac levels of the endocannabinoid 2-AG 24 h after infarction, but no changes in anandamide, palmitoylethanolamide, and oleoylethanolamide. This was a consequence of an increased expression of 2-AG synthesizing enzyme diacylglycerol lipase and a decrease of metabolizing enzyme monoacylglycerol lipase (MAGL) in infarcted hearts, as determined by quantitative RT-PCR analysis. The opposite mRNA expression pattern was observed in bone marrow. Pharmacological blockade of MAGL with JZL184 and thus increased systemic 2-AG levels in WT mice subjected to MI resulted in elevated cardiac CXCL1, CXCL2, and MMP9 protein levels as well as higher cardiac neutrophil and monocyte counts 24 h after infarction compared with vehicle-treated mice. Increased post-MI inflammation in these mice led to an increased infarct size, an impaired ventricular scar formation assessed by histology and a worsened cardiac function in echocardiography evaluations up to 21 days. Likewise, JZL184-administration in a myocardial ischaemia-reperfusion model increased cardiac myeloid cell recruitment and resulted in a larger fibrotic scar size. Conclusion These findings suggest that changes in endocannabinoid gradients due to altered tissue levels contribute to myeloid cell recruitment from the bone marrow to the infarcted heart, with crucial consequences on cardiac healing and function., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Backgrund New-onset atrial fibrillation complicating acute myocardial infarction represents an important challenge, with prognostic significance. Objective To study the incidence, impact on therapy and mortality, and to identify predictors of development of new-onset atrial fibrillation during hospital stay for ST-segment elevation myocardial infarction. Methods We studied all patients with ST-elevation myocardial infarction included consecutively, between 2010 and 2017, in a Portuguese national registry and compared two groups: 1 - no atrial fibrillation and 2 - new-onset atrial fibrillation. We adjusted a logistic regression model data analysis to assess the impact of new-onset atrial fibrillation on in-hospital mortality and to identify independent predictors of its development. A p value < 0.05 was considered significant. Results We studied 6325 patients, and new-onset atrial fibrillation was found in 365 (5.8%). Reperfusion was successfully accomplished in both groups with no difference regarding type of reperfusion. In group 2, therapy with beta-blockers and angiotensin-conversion enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) was less frequent, 20.6% received anticoagulation at discharge and 16.1% were on triple therapy. New-onset atrial fibrillation was associated with more in-hospital complications and mortality. However, it was not found as an independent predictor of in-hospital mortality. We identified age, prior stroke, inferior myocardial infarction and complete atrioventricular block as independent predictors of new-onset atrial fibrillation. Conclusion New-onset atrial fibrillation remains a frequent complication of myocardial infarction and is associated with higher rate of complications and in-hospital mortality. Age, prior stroke, inferior myocardial infarction and complete atrioventricular block were independent predictors of new onset atrial fibrillation. Only 36.7% of the patients received anticoagulation at discharge.

Rationale: Short-term mechanical circulatory support is increasingly used in the management of cardiogenic shock, but data from controlled studies are sparse. Thus, real-life data on complication rates and predictors of adverse outcome are important. Objective: The objective of this study was to analyse the experience with Impella devices in the management of profound cardiogenic shock. Methods and results: A retrospective study of 109 consecutive patients with severe shock after myocardial infarction, acute heart failure, or cardiac surgery. Possible device-related complications were registered and predictors of death while on Impella support and within 180 days were identified. In 79 patients (72%) cardiogenic shock was caused by myocardial infarction, acute heart failure in 16 (15%) and post-cardiotomy shock in 14 patients (13%). Thirty-five patients (32%) were comatose after cardiac arrest and in seven, the Impella was placed during chest compression. Mean age was 62±12 years, mean arterial pressure was 57±13 mmHg, pH 7.19±0.17 and lactate 7.5±5.7 mmol/l (range 1.8–30.0 mmol/l) at placement. During Impella therapy, 26 patients (28%) died among patients with myocardial infarction or acute heart failure. Of data available prior to placement lactate (hazard ratio 1.14, 95% confidence interval 1.04–1.25, P=0.004) was the only predictor of death on support. During support, five patients (5%) developed leg ischaemia requiring intervention. Bleeding from the Impella insertion site was seen in 14 patients (13%). Conclusion: Impella treatment is feasible in profound cardiogenic shock at an acceptable rate of complications. Despite an aggressive approach to restore cardiac output, mortality was high. Besides the severity of lactic acidosis there were no strong predictors of early death.

BACKGROUND: Patients with atrial fibrillation (AF) have increased risk of thromboembolic events such as stroke and myocardial infarction (MI). Although it has been established that the efficacy of anticoagulation is superior to that of antiplatelet agents for stroke prophylaxis in AF, the optimal antithrombotic treatment remains uncertain for primary protection against MI.OBJECTIVES: The authors investigated the incidence of first-time MI in patients with AF according to antithrombotic treatment and estimated the risk of stroke and bleeding.METHODS: Subjects with first-time AF diagnosed from 1997 to 2012 without history of coronary artery disease were identified using Danish nationwide administrative registries. Subjects were divided into time varying exposure groups according to antithrombotic treatment. The relative risks of outcomes were estimated by Poisson regression models.RESULTS: A total of 71,959 patients (median 75 years of age; females: 47%). At baseline, 37,539 patients (52%) were treated with vitamin K antagonist (VKA) monotherapy, 25,458 (35%) with acetylsalicylic acid (ASA) monotherapy and 8,962 (13%) with dual-therapy (VKA + ASA). The incidence of MI was 3% (n = 2,275). Relative to the VKA-treated group, the associated risk of MI was significantly higher for ASA (incidence rate ratio [IRR]: 1.54; 95% confidence interval [CI]: 1.40 to 1.68) and dual-therapy (IRR: 1.22; 95% CI: 1.06 to 1.40). The bleeding risk was significantly higher for dual-therapy (IRR: 1.93; 95% CI: 1.81 to 2.07). The risk of stroke relative to that of VKA therapy was significantly higher for both ASA (IRR: 2.00; 95% CI: 1.88 to 2.12) and dual-therapy (IRR: 1.30; 95% CI: 1.18 to 1.43).CONCLUSIONS: VKA monotherapy in patients with AF was associated with a lower risk of first-time MI and stroke than ASA monotherapy. Combination of ASA and VKA therapy was not associated with a lower risk of MI but was associated with increased bleeding risk.