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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

We aimed to evaluate the diagnostic agreement between radiofrequency (RF) intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for thin-cap fibroatheroma (TCFA) in non-infarct-related coronary arteries (non-IRA) in patients with ST-segment elevation myocardial infarction (STEMI). In the Integrated Biomarker Imaging Study (IBIS-4), 103 STEMI patients underwent OCT and RF-IVUS imaging of non-IRA after successful primary percutaneous coronary intervention and at 13-month follow-up. A coronary lesion was defined as a segment with ≥ 3 consecutive frames (≈1.2 mm) with plaque burden ≥ 40% as assessed by grayscale IVUS. RF-IVUS-derived TCFA was defined as a lesion with > 10% confluent necrotic core abutting to the lumen in > 10% of the circumference. OCT-TCFA was defined by a minimum cap thickness

Background We aimed to analyse initiation of and persistence with P2Y12 inhibitors after first-time myocardial infarction (MI). Methods and results Using Danish nationwide registries, we identified patients ≥30 years with first-time MI during 1 January 2005–30 June 2016 and subsequent prescriptions of P2Y12 inhibitors. Independent factors related to initiation of and persistence with P2Y12 inhibitors were analysed by multivariable logistic regression and a Cox proportional hazards model. Patients were stratified by revascularization strategy: percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or medical therapy alone (MTA). Overall, 79 597 MI patients were included with 39 172 undergoing PCI, 2619 CABG, and 16 640 MTA, showing initiation of P2Y12 inhibitors of 93.4%, 49.0%, and 51.5%, respectively. Congestive heart failure, cerebrovascular disease, cardiac dysrhythmias, renal failure, previous bleeding, and oral anticoagulants were associated with less initiation of P2Y12 inhibitors. Female sex was associated with less initiation of P2Y12 inhibitors following MTA. MTA, coronary angiography, cerebrovascular disease, diabetes with complications, previous bleeding, antidiabetics, and ticagrelor as P2Y12 inhibitor were associated with non-persistence, whereas female sex, advanced age, and concomitant pharmacotherapy with angiotensin-converting enzyme inhibitors, beta-blockers, statins, oral anticoagulants, and aspirin were associated with high persistence. Conclusion Initiation of P2Y12 inhibitors in PCI-treated MI patients was high in contrast to those treated with CABG or MTA and patients with certain comorbidities. Further studies on the benefit–risk ratio of P2Y12 inhibitors in CABG-treated or MTA-treated patients and patients with comorbidities after first-time MI are warranted, as is focus on persistence among patients receiving MTA, patients with comorbidities, and users of ticagrelor.

In patients with ST-elevation myocardial infarction (STEMI) the immune system is activated with an inflammatory response to follow. In STEMI patients with a severe inflammatory response, risk of development of cardiogenic shock (CS) seems increased. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a glycoprotein released from mature neutrophils and plasma concentration may increase immediately after STEMI. We therefore aimed to assess whether admission NGAL plasma concentration in patients with STEMI was associated with CS development after leaving the catheterization laboratory (late CS) and 30-day all-cause mortality. PATIENTS AND METHODS: From 1,892 consecutive patients with STEMI 1,626 (86%) had plasma NGAL concentration measured upon hospital admission before angiography throughout a 1-year period at two tertiary heart centers in Denmark. Patients were stratified according to NGAL quartiles (Q1-4). To assess late CS development, we adjusted for the Observatoire Régional Breton sur l'Infarctus risk score for late CS. For mortality assessment, we adjusted for gender, age, post-PCI culprit Thrombolysis in myocardial infarction flow, left ventricular ejection fraction (LVEF), kidney dysfunction, and being comatose after cardiac arrest. RESULTS: Increasing NGAL concentration was associated with higher age, more comorbidities, and more critical patient conditions including lower blood pressure and LVEF. When adjusted for factors associated with poor outcome, NGAL remained independently associated with both late CS development (Q4 vs. Q1-3) (OR (95% CI) 3.64 (1.79-7.41) and 30-day mortality (HR (95% CI) 3.18 (1.73-5.84)). CONCLUSION: Admission plasma concentration of NGAL in STEMI patients is independently associated with 30-day all-cause mortality and predictive of late CS development.

Aims: The obesity paradox suggests a better prognosis in overweight or obese patients with heart failure and acute myocardial infarction (AMI) than patients with normal weight. Few studies have investigated the association between BMI and mortality in patients with AMI complicated by cardiogenic shock (AMICS). The aim of this study was to evaluate the association between BMI and 30-day mortality in patients with AMICS. Methods and Results: A retrospective study of 1,716 patients with AMICS treated at 2 tertiary centers in south-eastern Denmark between 2010 and 2017. Patients undergoing revascularization and who were admitted to the intensive care unit were included (n = 1,216). BMI was available in 1,017 patients (83.6%). Patients were divided according to the WHO classification as normal weight BMI 2 (n = 453), overweight BMI 25–29.9 kg/m2 (n = 391), obese class 1 BMI 30–34.9 kg/m2 (n = 131), and obese class 2 + 3 BMI >35 kg/m2 (n = 42). Differences in baseline characteristics, in-hospital treatment, and the primary outcome of all-cause mortality at 30 days were examined. Obese patients had more comorbidities such as diabetes, hypertension, and dyslipidemia than patients with normal weight. Need for renal replacement therapy was higher among obese patients (normal weight, 19% vs. obese class 2 + 3, 35%, p = 0.02); otherwise, no difference in management was found. No difference in 30-day mortality was observed between groups (normal weight 44%, overweight 38%, obese class 1 41%, and obese class 2 + 3 45% at 30 days; ns). Conclusions: Thirty-day mortality in patients with AMICS was not associated with the BMI category. Thus, evidence of an “obesity paradox” was not observed in this contemporary cohort of patients with AMICS in Denmark.

ST-segment elevation myocardial infarction (STEMI) is clinically diagnosed by significant ST-segment elevation (STE) in the electrocardiogram (ECG). The importance of the sum of significant ST-segment elevation (∑STE) before primary percutaneous coronary intervention (PPCI) - considered an indicator of the degree of ischemia - is sparse. We evaluated the association of ∑STE before PPCI with respect to area at risk, infarct size and myocardial salvage.A total of 503 patients with STEMI and available cardiac magnetic resonance (CMR) were included. CMR was performed at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 92 (IQR, 88-96). The ECG before PPCI with the most prominent STE was used for analysis.∑STE divided into quartiles were progressive linearly associated with area at risk (p 0.001), final infarct size (p 0.001) and extent of microvascular obstruction (p 0.001) and inverse linearly associated with final myocardial salvage (p 0.001). Similar results were found for linear regression analyses. However, ∑STE was not associated with final myocardial salvage in patients with pre-PCI TIMI (thrombolysis in myocardial infarction) flow 0/1 (p = 0.24) in contrast to patients with pre-PCI TIMI flow 2/3 (p ≤ 0.001).In patients with STEMI presenting within 12 h of symptom onset, the degree of STE in the ECG before PPCI is a marker of the extent of myocardium at risk that in turn affects the infarct size in patients with pre-PCI TIMI flow 0/1, whereas the degree of STE in patients with pre-PCI TIMI flow 2/3 is a marker of the extent of the myocardium at risk as well as myocardial salvage - both affecting the myocardial damage.

Purpose: To validate the IABP-SHOCK II risk score in a Danish cohort and assess the association between the IABP-SHOCK II risk score and admission concentration of biomarkers reflecting neurohormonal–(Copeptin, Pro-atrial natriuretic peptide (proANP), Mid-regional pro-adrenomedullin (MRproADM)) and inflammatory (ST2) activation in patients with CS complicating ST segment elevation myocardial infarction (STEMI). Methods: A total of 137 consecutive patients admitted with STEMI and CS at two tertiary heart centres were stratified according to the IABP-SHOCK II risk score (0–2; 3/4; 5–9), and had blood sampled upon admission. Results: Plasma concentrations of Copeptin (median (pmol/L) score 0–2: 313; score 3/4: 682; score 5–9: 632 p < 0.0001), proANP (pmol/L) (1459; 2225; 2876 p = 0.0009) and MRproADM (nmol/L) (0.86; 1.2; 1.4 p = 0.04) were significantly associated with the risk score, whereas ST2 (ng/mL) was not (44; 60; 45 p = 0.23). The IABP-SHOCK II risk score predicted 30-day mortality (score 0–2: 22%; score 4/3: 51%; score 5–9: 72%, area under the curve (AUC): 0.73, plogrank < 0.0001), while the tested biomarkers did not (AUC: 0.51

Background As existing results are diverging, and the patient population has changed significantly, this study sought to investigate the prognostic importance of the culprit lesion location in patients with cardiogenic shock due to myocardial infarction (AMICS), in a contemporary and unselected patient population. Methods From the recruitment area of two tertiary heart centres in Denmark, covering 3.9 million citizens corresponding to two-thirds of the Danish population, all AMICS patients in the period of 2010–2017 were individually identified and validated through patient records. Results A total of 1716 patients with AMICS were identified. Immediate revascularization was performed in 1482 patients (86%). Among these, a culprit lesion in the left main coronary artery (LM) was associated with the highest 30-day mortality rate (66%), plogrank Conclusions Among AMICS patients undergoing revascularization, a LM culprit lesion was associated with the highest short-term mortality, whereas patients with a culprit lesion in the remaining coronary arteries had comparable and lower mortality rates. Multivessel disease patients had similar prognoses irrespective of percutaneous coronary intervention approach and whether partial or complete revascularization was achieved.

Background Up to 40% of patients with ST-segment elevation myocardial infarction (STEMI) present later than 12 hours after symptom onset. However, data on clinical outcomes in STEMI patients treated with primary percutaneous coronary intervention (PCI) ≥12 hours after symptom onset are non-existent. We evaluated the association between primary PCI performed later than 12 hours after symptom onset and clinical outcomes in a large all-comer contemporary STEMI cohort. Methods All STEMI patients treated with primary PCI in eastern Denmark from November 2009 to November 2016 were included and stratified by timing of the PCI. The combined clinical endpoint of all-cause mortality and hospitalisation for heart failure was identified from nationwide Danish registries. Results We included 6674 patients: 6108 (92%) were treated 0.001 for all). Late presentation was independently associated with an increased risk of an adverse clinical outcome (hazard ratio 1.42, 95% confidence interval 1.22–1.66; P < 0.001). Conclusions Increasing duration from symptom onset to primary PCI was associated with an increased risk of an adverse clinical outcome in patients with STEMI, especially when the delay exceeded 12 hours.

Clinical decision-making in patients with ST-segment elevation myocardial infarction (STEMI) presenting beyond 12 h of symptom onset (late presenters) is challenging. However, the electrocardiogram (ECG) may provide helpful information. We investigated the association between three ECG-scores and myocardial salvage and infarct size in late presenters treated with primary percutaneous coronary intervention (primary PCI).Sixty-six patients with STEMI and ongoing symptoms presenting 12-72 h after symptom onset were included. Cardiac magnetic resonance was performed at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 93 (IQR, 90-98). The pre-PCI ECG was analyzed for the presence of pathological QW (early QW) as well as Anderson-Wilkins acuteness score (AW-score), the classic Sclarovsky-Birnbaum Ischemia Grading System (classic SB-IG-score) and a modified SB-IG-score including any T-wave morphologies.Early QW was associated with a larger myocardium at risk (39 ± 12 versus 33 ± 12; p = 0.030) and final infarct size (20 ± 11 versus 14 ± 9; p = 0.021) as well as a numerical lower final myocardial salvage (0.52 ± 0.19 versus 0.61 ± 0.23; p = 0.09). The association with final infarct size disappeared after adjusting for myocardium at risk. An AW-score 3 showed a trend towards a larger final infarct size (18 ± 11 versus 11 ± 11; p = 0.08) and was not associated with salvage index (0.55 ± 0.20 versus 0.65 ± 0.30; p = 0.23). The classic and modified SB-IG-score were not associated with final infarct size (modified SB-IG-score, 17 ± 10 versus 21 ± 13; p = 0.28) or final myocardial salvage (0.53 ± 0.20 versus 0.53 ± 0.26; p = 0.96).Of three well-established ECG-scores only early QW and AW-score 3 showed association with myocardium at risk and infarct size to some extent, but the association with myocardial salvage was weak. Hence, neither of the three investigated ECG-scores are sufficient to guide clinical decision-making in patients with STEMI and ongoing symptoms presenting beyond 12 h of symptom onset.

Background: Patients with severe aortic stenosis frequently have coexisting coronary artery disease. Invasive hyperemic and nonhyperemic pressure indices are used to assess coronary artery disease severity but have not been evaluated in the context of severe aortic stenosis. Methods: We compared lesion reclassification rates of fractional flow reserve (FFR) and resting full-cycle ratio (RFR) measured before and 6 months after transcatheter aortic valve implantation using the conventional clinical cutoffs of ≤0.80 for FFR and ≤0.89 for RFR. This was a substudy of the ongoing NOTION-3 trial (Third Nordic Aortic Valve Intervention). Two-dimensional quantitative coronary analysis was used to assess changes in angiographic lesion severity. Results: Forty patients were included contributing 50 lesions in which FFR was measured. In 32 patients (36 lesions), RFR was also measured. There was no significant change in diameter stenosis from baseline to follow-up, 49.8% (42.9%–57.1%) versus 52.3% (43.2%–57.8%), P =0.50. RFR improved significantly from 0.88 (0.83%–0.93) at baseline to 0.92 (0.83–0.95) at follow-up, P =0.003, whereas FFR remained unchanged, 0.84 (0.81–0.89) versus 0.86 (0.78–0.90), P =0.72. At baseline, 11 out of 50 (22%) lesions were FFR-positive, whereas 15 out of 50 (30%) were positive at follow-up, P =0.219. Corresponding numbers for RFR were 23 out of 36 (64%) at baseline and 12 out of 36 (33%) at follow-up, P =0.003. Conclusions: In patients with severe aortic stenosis, physiological assessment of coronary lesions with FFR before transcatheter aortic valve implantation leads to lower reclassification rate at 6-month follow-up, compared with RFR.

BACKGROUND: To compare effectiveness and safety of clopidogrel, prasugrel, and ticagrelor among all-comers with ST-segment elevation myocardial infarction (STEMI) and extend the knowledge from randomized clinical trials.METHODS: All consecutive patients with STEMI admitted to Copenhagen University Hospital, Rigshospitalet, from 2009 to 2016 were identified via the Eastern Danish Heart Registry. By individual linkage to Danish nationwide registries, claimed drugs and end points were obtained. Patients alive a week post-discharge were included, stratified according to clopidogrel, prasugrel, or ticagrelor treatment, and followed for a year. The effectiveness end point (a composite of all-cause mortality, recurrent myocardial infarction, and ischemic stroke) and safety end point (a composite of bleedings leading to hospitalization) were assessed by multivariate Cox proportional-hazards models.RESULTS: In total, 5123 patients were included (clopidogrel [1245], prasugrel [1902], ticagrelor [1976]) with ≥95% treatment persistency. Concomitant use of aspirin was ≥95%. Females accounted for 24% and elderly for 17%. Compared with clopidogrel, the effectiveness end point occurred less often for ticagrelor (HR 0.50, 95% CI 0.35-0.70) and prasugrel (HR 0.48, 95% CI 0.33-0.68) without differences in bleedings leading to hospitalization. No differences in comparative effectiveness or safety were found between prasugrel and ticagrelor. Sensitivity analyses with time-dependent drug exposure and the period 2011-2015 showed similar results.CONCLUSIONS: Among all-comers with STEMI, ticagrelor and prasugrel were associated with reduced incidence of the composite end point of all-cause mortality, recurrent myocardial infarction, and ischemic stroke without an increase in bleedings leading to hospitalization compared with clopidogrel. No differences were found between prasugrel and ticagrelor.

We assessed the feasibility and the procedural and long-term safety of intracoronary (i.c) imaging for documentary purposes with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI in the setting of IBIS-4 study. IBIS4 (NCT00962416) is a prospective cohort study conducted at five European centers including 103 STEMI patients who underwent serial three-vessel coronary imaging during primary PCI and at 13 months. The feasibility parameter was successful imaging, defined as the number of pullbacks suitable for analysis. Safety parameters included the frequency of peri-procedural complications, and major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and any clinically-indicated revascularization at 2 years. Clinical outcomes were compared with the results from a cohort of 485 STEMI patients undergoing primary PCI without additional imaging. Imaging of the infarct-related artery at baseline (and follow-up) was successful in 92.2 % (96.6 %) of patients using OCT and in 93.2 % (95.5 %) using IVUS. Imaging of the non-infarct-related vessels was successful in 88.7 % (95.6 %) using OCT and in 90.5 % (93.3 %) using IVUS. Periprocedural complications occurred < 2.0 % of OCT and none during IVUS. There were no differences throughout 2 years between the imaging and control group in terms of MACE (16.7 vs. 13.3 %, adjusted HR1.40, 95 % CI 0.77-2.52, p = 0.27). Multi-modality three-vessel i.c. imaging in STEMI patients undergoing primary PCI is consistent a high degree of success and can be performed safely without impact on cardiovascular events at long-term follow-up.

Background The optimal timing of invasive examination and treatment of high‐risk patients with non–ST‐segment–elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard‐care invasive coronary angiography on the risk of all‐cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non–ST‐segment–elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48–72 hours) invasive strategy. The primary outcome of the present study was all‐cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow‐up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16–3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63–1.10]) ( P interaction =0.006). Conclusions In patients with non–ST‐segment–elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high‐risk and low‐risk patients with non–ST‐segment–elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02061891.

Background: Prognosis models based on stepwise regression methods show modest performance in patients with cardiogenic shock (CS). Automated variable selection allows data-driven risk evaluation by recognizing distinct patterns in data. We sought to evaluate an automated variable selection method (least absolute shrinkage and selection operator, LASSO) for predicting 30-day mortality in patients with acute myocardial infarction and CS (AMICS) receiving acute percutaneous coronary intervention (PCI) compared to two established scores.Methods and results: Consecutive patients with AMICS receiving acute PCI at one of two tertiary heart centres in Denmark 2010-2017. Patients were divided according to treatment with mechanical circulatory support (MCS); PCI-MCS cohort (n = 220) versus PCI cohort (n = 1180). The latter was divided into a development (2010-2014) and a temporal validation cohort (2015-2017). Cohort-specific LASSO models were based on data obtained before PCI. LASSO models outperformed IABP-SHOCK II and CardShock risk scores in discriminative ability for 30-day mortality in the PCI validation [receiver operating characteristics area under the curve (ROC AUC) 0.80 (95% CI 0.76-0.84) vs 0.73 (95% CI 0.69-0.77) and 0.70 (95% CI 0.65-0.75), respectively, P < 0.01 for both] and PCI-MCS development cohort [ROC AUC 0.77 (95% CI 0.70-0.83) vs 0.64 (95% CI 0.57-0.71) and 0.64 (95% CI 0.57-0.71), respectively, P < 0.01 for both]. Variable influence differed depending on MCS, with age being the most influential factor in the LASSO-PCI model, whereas haematocrit and estimated glomerular filtration rate were the highest-ranking factors in the LASSO-PCI-MCS model.Conclusion: Data-driven prognosis models outperformed established risk scores in patients with AMICS receiving acute PCI and exhibited good discriminative abilities. Observations indicate a potential use of machinelearning to facilitate individualized patient care and targeted interventions in the future. Background Prognosis models based on stepwise regression methods show modest performance in patients with cardiogenic shock (CS). Automated variable selection allows data-driven risk evaluation by recognizing distinct patterns in data. We sought to evaluate an automated variable selection method (least absolute shrinkage and selection operator, LASSO) for predicting 30-day mortality in patients with acute myocardial infarction and CS (AMICS) receiving acute percutaneous coronary intervention (PCI) compared to two established scores.Methods and results Consecutive patients with AMICS receiving acute PCI at one of two tertiary heart centres in Denmark 2010-2017. Patients were divided according to treatment with mechanical circulatory support (MCS); PCI-MCS cohort (n=220) versus PCI cohort (n=1180). The latter was divided into a development (2010-2014) and a temporal validation cohort (2015-2017). Cohort-specific LASSO models were based on data obtained before PCI. LASSO models outperformed IABP-SHOCK II and CardShock risk scores in discriminative ability for 30-day mortality in the PCI validation [receiver operating characteristics area under the curve (ROC AUC) 0.80 (95% CI 0.76-0.84) vs 0.73 (95% CI 0.69-0.77) and 0.70 (95% CI 0.65-0.75), respectively, PConclusion Data-driven prognosis models outperformed established risk scores in patients with AMICS receiving acute PCI and exhibited good discriminative abilities. Observations indicate a potential use of machinelearning to facilitate individualized patient care and targeted interventions in the future.[GRAPHICS]

Aims Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial. Methods and results We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10−54; CES1 G143E, P = 1.3 × 10−16; CYP2C19*17, P = 9.5 × 10−10; CYP2B6 1294 + 53 C > T, P = 3.0 × 10−4; CYP2B6 516 G > T, P = 1.0 × 10−3; CYP2C9*2, P = 1.2 × 10−3; and CYP2C9*3, P = 1.5 × 10−3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14–2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35–14.27, P = 0.01) compared to patients who carried six or fewer of these alleles. Conclusion Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.

AIMS: To assess the impact of sampling bias due to reported as well as unreported exclusion of the target population in a multi-center randomized controlled trial (RCT) of ST-elevation myocardial infarction (STEMI).METHODS AND RESULTS: We compared clinical characteristics and mortality between participants in the DANAMI-3 trial to contemporary non-participants with STEMI using unselected registries. A total of 179 DANAMI-3 participants (8%) and 617 contemporary non-participants (22%) had died (Log-Rank: P CONCLUSION: Sampling bias had occurred due to both reported and unreported exclusion of eligible patients and the difference in mortality between participants and non-participants could not be explained only by the trial exclusion criteria. Thus, screening logs may not be suited to address the risks of sampling bias.

Objectives This study assessed changes in optical coherence tomography (OCT)-defined plaque composition in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin treatment. Background OCT is a high-resolution modality capable of measuring plaque characteristics including fibrous cap thickness (FCT) and macrophage infiltration. There is limited in vivo evidence regarding the effects of statins on OCT-defined coronary atheroma composition and no evidence in the context of STEMI. Methods In the IBIS-4 (Integrated Biomarker Imaging Study-4), 103 patients underwent intravascular ultrasonography and OCT of 2 noninfarct-related coronary arteries in the acute phase of STEMI. Patients were treated with high-dose rosuvastatin for 13 months. Serial OCT imaging was available in 153 arteries from 83 patients. We measured FCT by using a semi-automated method. Co-primary endpoints consisted of the change in minimum FCT (measured in fibroatheromas) and change in macrophage line arc. Results At 13 months, median low-density lipoprotein cholesterol had decreased from 128 mg/dl to 73.6 mg/dl. Minimum FCT, measured in 31 lesions from 27 patients, increased from 64.9 ± 19.9 μm to 87.9 ± 38.1 μm (p = 0.008). Macrophage line arc decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p Conclusions In this observational study, we found significant increase in minimum FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other plaque phenotypes in nonculprit lesions of patients with STEMI treated with high-intensity statin therapy.

Aim: We sought to describe the contemporary annual incidence of cardiogenic shock (CS) following acute myocardial infarction (AMICS), the proportion of patients developing CS following ST-elevation myocardial infarction (STEMI), and other temporal changes in AMICS in Denmark between 2010 and 2017. Methods and results: Medical records of patients suspected of having AMICS during 2010–2017 were reviewed to identify consecutive patients with AMICS in a cohort corresponding to two-thirds of the Danish population. Due to changes in recruitment area over the study period, population-based incidence could only be calculated from 2012 to 2017. A total of 1716 patients with AMICS were identified and an increase in the annual incidence was observed, from a nadir 65.3 per million person-years in 2013 to 80.0 per million person-years in 2017 (P-value for trend < 0.001). This trend corresponded to an increase in patients with non-STEMI and a decrease in patients developing CS after STEMI (10.0–6.6%, P-value for trend < 0.001) Also, mean arterial blood pressure at the time of AMICS was lower (63 ± 11 mmHg to 61 ± 13 mmHg, P-value for trend = 0.001) and the frequency of patients with left ventricular ejection fraction ≤ 30% increased (61.8%–71.4%, P-value for trend = 0.004). The annual 30-day mortality during the study period remained unchanged at about 50%. Conclusion: The incidence rate of AMICS increased in the Danish population between 2012 and 2017. Fewer patients with STEMI developed CS, and haemodynamic severity of CS increased during the study period; however, survival rates remained unchanged.

Objectives The aim of this study was to describe the rates and causes of unplanned readmissions at different time periods following percutaneous coronary intervention (PCI). Background The rates and causes of readmission at different time periods after PCI remain incompletely elucidated. Methods Patients undergoing PCI between 2010 and 2014 in the U.S. Nationwide Readmission Database were evaluated for the rates, causes, predictors, and costs of unplanned readmission between 0 and 7 days, 8 and 30 days, 31 and 90 days, and 91 and 180 days after index discharge. Results This analysis included 2,412,000 patients; 2.5% were readmitted between 0 and 7 days, 7.6% between 8 and 30 days, 8.9% between 31 and 90 days, and 8.0% between 91 and 180 days (cumulative rates 2.5%, 9.9%, 18.0%, and 24.8%, respectively). The majority of readmissions during each time period were due to noncardiac causes (53.1% to 59.6%). Nonspecific chest pain was the most common identifiable noncardiac cause for readmission during each time period (14.2% to 22.7% of noncardiac readmissions). Coronary artery disease including angina was the most common cardiac cause for readmission during each time period (37.4% to 39.3% of cardiac readmissions). The second most common cardiac cause for readmission was acute myocardial infarction between 0 and 7 days (27.6% of cardiac readmissions) and heart failure during all subsequent time periods (22.2% to 23.7% of cardiac readmissions). Conclusions Approximately 25% of patients following PCI have unplanned readmissions within 6 months. Causes of readmission depend on the timing at which they are assessed, with noncardiovascular causes becoming more important at longer time points.

Objectives The aim of this study was to evaluate the effect of fractional flow reserve (FFR)–guided revascularization compared with culprit-only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) on infarct size, left ventricular (LV), function, LV remodeling, and the presence of nonculprit infarctions. Background Patients with STEMI with multivessel disease might have improved clinical outcomes after complete revascularization compared with PCI of the infarct-related artery only, but the impact on infarct size, LV function, and remodeling as well as the risk for periprocedural infarction are unknown. Methods In this substudy of the DANAMI-3 (Third Danish Trial in Acute Myocardial Infarction)–PRIMULTI (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization) randomized trial, patients with STEMI with multivessel disease were randomized to receive either complete FFR-guided revascularization or PCI of the culprit vessel only. The patients underwent cardiac magnetic resonance imaging during index admission and at 3-month follow-up. Results A total of 280 patients (136 patients with infarct-related and 144 with complete FFR-guided revascularization) were included. There were no differences in final infarct size (median 12% [interquartile range: 5% to 19%] vs. 11% [interquartile range: 4% to 18%]; p = 0.62), myocardial salvage index (median 0.71 [interquartile range: 0.54 to 0.89] vs. 0.66 [interquartile range: 0.55 to 0.87]; p = 0.49), LV ejection fraction (mean 58 ± 9% vs. 59 ± 9%; p = 0.39), and LV end-systolic volume remodeling (mean 7 ± 22 ml vs. 7 ± 19 ml; p = 0.63). New nonculprit infarction occurring after the nonculprit intervention was numerically more frequent among patients treated with complete revascularization (6 [4.5%] vs. 1 [0.8%]; p = 0.12). Conclusions Complete FFR-guided revascularization in patients with STEMI and multivessel disease did not affect final infarct size, LV function, or remodeling compared with culprit-only PCI.

The link between cardiac autonomic neuropathy and risk of cardiovascular disease is highlighted as an area in which research is needed. This study was undertaken to evaluate the association between measures of cardiac autonomic function and cardiac vascular function in type 1 diabetes using new and sensitive methods. This was a cross-sectional study in patients with type 1 diabetes, stratified by normoalbuminuria (n = 30) and macroalbuminuria (n = 30), and in healthy control subjects (n = 30). Cardiac autonomic function was evaluated using heart rate variability (HRV) indices, cardiovascular autonomic reflex tests (CARTs), and cardiac 123I-metaiodobenzylguanidine (MIBG) imaging. Cardiac vascular function was assessed as myocardial flow reserve (MFR) measured by cardiac 82Rb-positron emission tomography/computed tomography. The measures of cardiac autonomic function (except low frequency–to–high frequency ratio and the Valsalva test ratio) were positively correlated to MFR in unadjusted analysis. All the HRV indices lost significance after adjustment for age and heart rate. After further adjustment for relevant cardiovascular risk factors, the late heart-to-mediastinum ratio directly measuring the function of adrenergic receptors and sympathetic integrity (from the MIBG scintigraphy) and the 30-to-15 ratio (a CART), remained positively associated with MFR (P ≤ 0.04). Cardiac autonomic dysfunction, including loss of cardiac sympathetic integrity in type 1 diabetes, is associated with and may contribute to impaired myocardial blood flow regulation.

AIMS: The diagnosis of cardiogenic shock depends on clinical signs of poor perfusion and low blood pressure. Lactate concentration will increase with poor tissue perfusion, and it has prognostic value in cardiogenic shock patients. We sought to assess the prognostic value of lactate concentration in subjects admitted with suspected ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: In 2,094 (93%) out of 2,247 consecutive suspected STEMI-subjects, lactate concentration was measured on admission. The prognostic value of lactate concentration on 30-day mortality was assessed in addition to clinical signs of peripheral hypoperfusion, systolic blood pressure (sBP), and left ventricular ejection fraction (LVEF) in multivariable models.Lactate concentration added prognostic information beyond signs of peripheral hypoperfusion, sBP, and LVEF, and was independently associated with 30-day mortality (hazard ratio [95% confidence interval] 1.11 [1.07-1.14], P

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. Results: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1–4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78–1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67–1.01; P value for interaction=0.023). Conclusions: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Background Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. Methods This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan–Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. Results A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow–Pittsburgh Cerebral Performance Categories 1–2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow 6.8 and lactate 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52–0.76). Conclusions A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

PURPOSE OF REVIEW: Acute revascularization is with some evidence the only intervention proven to improve the prognosis in myocardial infarction-related cardiogenic shock but several interventions are continuously being investigated in order to increase survival among these patients. In this review, several aspects related to the interventional treatment of cardiogenic shock are discussed chronologically from symptom debut to leaving the cardiac catheterization laboratory. RECENT FINDINGS: In the randomized CULPRIT-SHOCK trial, a culprit-only revascularization strategy was reported superior to immediate complete revascularization among patients with multivessel disease. Recent large-scale observational data underline the marked prognostic importance of time from medical contact to revascularization in acute myocardial infarction-related cardiogenic shock. Moreover, studies suggest a potential beneficial effect of a transradial vascular access as well as early initialization of mechanical circulatory support in carefully selected patients. This, however, needs further validation. SUMMARY: Acute revascularization remains a crucial part of the initial management of acute myocardial infarction-related cardiogenic shock. Among cardiogenic shock patients presenting with multivessel disease, a culprit-only approach should be the routine strategy. Time to revascularization plays a crucial role in the setting of cardiogenic shock, why prehospital optimization and triaging may be the most important factors in order to improve prognosis in AMI-related cardiogenic shock.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Rigshospitalets Forskningsfond (Grant number: 07IO) Hjerteforeningen (Grant number A6024) Lundbeckfonden (Grant number R186-2015-2132) BACKGROUND In patients with ST-elevation myocardial infarction (STEMI) increased inflammatory response is associated with development of cardiogenic shock (CS). Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a glycoprotein released from mature neutrophils and the plasma concentration of NGAL likely increases immediately after STEMI. PURPOSE We aimed to assess whether admission NGAL plasma concentration in patients with STEMI was associated with CS development after leaving the catheterization laboratory (late CS) and 30-day all-cause mortality. MATERIALS AND METHODS From 1892 consecutive patients with STEMI 1626 (86%) had plasma NGAL concentration measured upon hospital admission before angiography throughout a 1-year period at two tertiary heart centers in Denmark. Patients were stratified according to NGAL quartiles (Q1-4). To assess late CS development, we adjusted for the Observatoire Régional Breton sur l’Infarctus (ORBI) risk score for late CS. For mortality assessment, we adjusted for gender, age, post-PCI culprit Thrombolysis in myocardial infarction (TIMI) flow, left ventricular ejection fraction (LVEF), kidney dysfunction, admission lactate concentration and being comatose after cardiac arrest. RESULTS Increasing NGAL concentration was associated with higher age, more comorbidities (hypertension, diabetes, heart failure, previous stroke, and kidney dysfunction) and more critical patient conditions at presentation including lower blood pressure and LVEF. Plasma NGAL concentration was associated with both late CS development and 30-day mortality (Figure). When adjusted for factors associated with poor outcome, NGAL remained independently associated with both late CS development (Q4 vs. Q1-3) (OR (95% CI) 2.64 (1.57-6.03)) and 30-day mortality (HR (95% CI) 3.18 (1.46-6.93)). CONCLUSION High admission plasma concentration of NGAL in patients with STEMI was independently associated late CS development and 30-day all-cause mortality. Abstract Figure. NGAL quartiles and late CS/mortality

Background: Coronary collateral circulation and conditioning from remote ischemic coronary territories may protect culprit myocardium in the elderly, and younger STEMI patients could suffer from larger infarcts. We evaluated the impact of age on myocardial salvage and long-term prognosis in a contemporary STEMI cohort. Methods: Of 1603 included STEMI patients 807 underwent cardiac magnetic resonance. To assess the impact of age on infarct size and left ventricular ejection fraction (LVEF) as well as the composite endpoint of death and re-hospitalization for heart failure we stratified the patients by an age cut-off of 60 years. Results: Younger STEMI patients had smaller final infarcts (10% vs. 12%, P = 0.012) and higher final LVEF (60% vs. 58%, P = 0.042). After adjusting for multiple potential confounders age did not remain significantly associated with infarct size and LVEF. During 4-year follow-up, the composite endpoint occurred less often in the young (3.2% vs. 17.2%; P < 0.001) with a univariate hazard ratio of 5.77 (95% CI, 3.75–8.89; p < 0.001). Event estimates of 4 subgroups (young vs. elderly and infarct size beyond vs. below median) showed a gradual increase in the occurrence of the composite endpoint depending on both age and acute infarct size (log-rank p < 0.001). Conclusion: Having a STEMI after entering the seventh decade of life more than quadrupled the risk of future death or re-hospitalization for heart failure. Risk of death and re-hospitalization depended on both advanced age and infarct size, albeit no substantial difference was found in infarct size, LVEF and salvage potential between younger and elderly patients with STEMI.

Bleeding after acute myocardial infarction (AMI) is associated with an increased morbidity and mortality. The frequency and consequences of bleeding events in patients with AMICS are not well described. The objective was to investigate incidence and outcome of bleeding complications among unselected patients with AMI complicated by cardiogenic shock (AMICS) and referred for immediate revascularization. Bleeding events were assessed by review of medical records in consecutive AMICS patients admitted between 2010 and 2017. Bleedings during admission were classified according to Bleeding Academic Research Consortium classification. Patients who did not survive to admission in the intensive care unit were excluded. Of the 1,716 patients admitted with AMICS, 1,532 patients (89%) survived to ICU admission. At 30 days, mortality was 48%. Severe bleedings classified as BARC 3/5 were seen in 87 non-coronary bypass grafting patients (6.1%). Co-morbidity did not differ among patients; however, patients who had a BARC 3/5 bleeding had significantly higher lactate and lower systolic blood pressure at admission, indicating a more severe state of shock. The use of mechanical assist devices was significantly associated with severe bleeding events. Univariable analysis showed that patients with a BARC 3/5 bleeding had a significantly higher 30-day mortality hazard compared with patients without severe bleedings. The association did not sustain after multivariable adjustment (hazard ratio 0.90, 95% confidence interval 0.64; 1.26, p = 0.52). In conclusion, severe bleeding events according to BARC classification in an all-comer population of patients with AMICS were not associated with higher mortality when adjusting for immediate management, hemodynamic, and metabolic state. This indicates that mortality in these patients is primarily related to other factors.

Background Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). Methods PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Findings Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17 women, 745 [83 men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2 951.0-15.6) of 898 patients, with 66 (8.0 95.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9[SD 15.9]). Highly lipidic lesions (851 [24 of 3500 lesions, present in 520 [59 of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22 of 3629 lesions, present in 530 [59 of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.095.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.295.4-17.6). Interpretation Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. Copyright (C) 2021 Elsevier Ltd. All rights reserved. BackgroundNear-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).MethodsPROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.FindingsBetween June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55–70] years). Median follow-up was 3·7 (IQR 3·0–4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0–15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2–10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25–4·13) and non-culprit lesion-specific MACEs (7·83, 4·12–14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0–10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4–17·6).InterpretationCombined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.FundingAbbott Vascular, Infraredx, and The Medicines Company.

Background Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non–ST-segment elevation acute coronary syndrome (NSTEACS). Objectives This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. Methods The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non–high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. Results Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non–high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). Conclusions Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891 )

BACKGROUND: New-onset atrial fibrillation (NEW-AF) following ST-segment elevation myocardial infarction (STEMI) is a common complication, but the true prognostic impact of NEW-AF is unknown. Additionally, the optimal treatment of NEW-AF among patients with STEMI is warranted.METHODS: A large cohort of consecutive patients with STEMI treated with percutaneous coronary intervention were identified using the Eastern Danish Heart Registry from 1999-2016. Medication and end points were retrieved from Danish nationwide registries. NEW-AF was defined as a diagnosis of AF within 30 days following STEMI. Patients without a history of AF and alive after 30 days after discharge were included. Incidence rates were calculated and multivariate analyses performed to determine the association between NEW-AF and long-term mortality, incidence of ischemic stroke, re-MI, and bleeding leading to hospitalization, and the comparative effectiveness of OAC therapy on these outcomes.RESULTS: Of 7944 patients with STEMI, 296 (3.7%) developed NEW-AF. NEW-AF was associated with increased long-term mortality (adjusted HR 1.48, 95% CI 1.20-1.82, PCONCLUSIONS: NEW-AF following STEMI is associated with increased long-term mortality. Treatment with OAC therapy in NEW-AF patients is associated with reduced long-term mortality.

Background Early and correct diagnosis of ST-segment elevation myocardial infarction (STEMI) is crucial for providing timely reperfusion therapy. Patients with ischemic symptoms presenting with ST-segment elevation on the electrocardiogram (ECG) are preferably transported directly to a catheterization laboratory (Cath-lab) for primary percutaneous coronary intervention (PPCI). However, the ECG often contains confounding factors making the STEMI diagnosis challenging leading to false positive Cath-lab activation. The objective of this study was to test the performance of a standard automated algorithm against an additional high specificity setting developed for reducing the false positive STEMI calls. Methods We included consecutive patients with an available digital prehospital ECG triaged directly to Cath-lab for acute coronary angiography between 2009 and 2012. An adjudicated discharge diagnosis of STEMI or no myocardial infarction (no-MI) was assigned for each patient. The new automatic algorithm contains a feature to reduce false positive STEMI interpretation. The STEMI performance with the standard setting (STD) and the high specificity setting (HiSpec) was tested against the adjudicated discharge diagnosis in a retrospective manner. Results In total, 2256 patients with an available digital prehospital ECG (mean age 63 ± 13 years, male gender 71%) were included in the analysis. The discharge diagnosis of STEMI was assigned in 1885 (84%) patients. The STD identified 165 true negative and 1457 true positive (206 false positive and 428 false negative) cases (77.3%, 44.5%, 87.6% and 17.3% for sensitivity, specificity, PPV and NPV, respectively). The HiSpec identified 191 true negative and 1316 true positive (180 false positive and 569 false negative) cases (69.8%, 51.5%, 88.0% and 25.1% for sensitivity, specificity, PPV and NPV, respectively). From STD to HiSpec, false positive cases were reduced by 26 (12,6%), but false negative results were increased by 33%. Conclusions Implementing an automated ECG algorithm with a high specificity setting was able to reduce the number of false positive STEMI cases. However, the predictive values for both positive and negative STEMI identification were moderate in this highly selected STEMI population. Finally, due the reduced sensitivity/increased false negatives, a negative AMI statement should not be solely based on the automated ECG statement.

BACKGROUND: Cardiac Rubidium-82 (82 Rb) positron emission tomography/computed tomography (PET/CT) provides a measure of the myocardial blood flow and the myocardial flow reserve, which reflects the function of both large epicardial arteries and the myocardial microcirculation. Knowledge on changes in the myocardial microvascular function over time is lacking.METHODS: In this cohort study, we recruited 60 persons with type 2 diabetes and 30 non-diabetic controls, in 2013; all free of overt cardiovascular disease. All underwent a cardiac 82 Rb PET/CT scan. In 2019, all survivors (n = 82) were invited for a repeated cardiac 82 Rb PET/CT scan using the same protocol, and 29 with type 2 diabetes and 19 controls participated.RESULTS: Median duration between visits was 6.2 years (IQR: 6.1-6.3). In the total cohort, the mean age was 66.4 years (SD: 9.3) and 33% were females. The myocardial flow reserve was lower in persons with type 2 diabetes compared to controls (p = 0.002) but there was no temporal change in the myocardial flow reserve in participants with type 2 diabetes: mean change: -0.22 (95% CI: -0.47 to 0.02) nor in controls: -0.12 (-0.49 to 0.25) or when comparing type 2 diabetes to controls: mean difference: -0.10 (95% CI: -0.52 to 0.31). The temporal reduction in stress-induced myocardial blood flow did not differ within the groups but was more pronounced in type 2 diabetes compared to controls: mean difference: -0.30 (95% CI: -0.55 to -0.04).CONCLUSION: The myocardial microvascular function was impaired in persons with type 2 diabetes compared to controls but did not change significantly in either of the groups when evaluated over 6 years.

Background Cardiogenic shock (CS) is a heterogeneous syndrome with varied presentations and outcomes. We used a machine learning approach to test the hypothesis that patients with CS have distinct phenotypes at presentation, which are associated with unique clinical profiles and in‐hospital mortality. Methods and Results We analyzed data from 1959 patients with CS from 2 international cohorts: CSWG (Cardiogenic Shock Working Group Registry) (myocardial infarction [CSWG‐MI; n=410] and acute‐on‐chronic heart failure [CSWG‐HF; n=480]) and the DRR (Danish Retroshock MI Registry) (n=1069). Clusters of patients with CS were identified in CSWG‐MI using the consensus k means algorithm and subsequently validated in CSWG‐HF and DRR. Patients in each phenotype were further categorized by their Society of Cardiovascular Angiography and Interventions staging. The machine learning algorithms revealed 3 distinct clusters in CS: "non‐congested (I)", "cardiorenal (II)," and "cardiometabolic (III)" shock. Among the 3 cohorts (CSWG‐MI versus DDR versus CSWG‐HF), in‐hospital mortality was 21% versus 28% versus 10%, 45% versus 40% versus 32%, and 55% versus 56% versus 52% for clusters I, II, and III, respectively. The "cardiometabolic shock" cluster had the highest risk of developing stage D or E shock as well as in‐hospital mortality among the phenotypes, regardless of cause. Despite baseline differences, each cluster showed reproducible demographic, metabolic, and hemodynamic profiles across the 3 cohorts. Conclusions Using machine learning, we identified and validated 3 distinct CS phenotypes, with specific and reproducible associations with mortality. These phenotypes may allow for targeted patient enrollment in clinical trials and foster development of tailored treatment strategies in subsets of patients with CS.

Aims The objective was to describe patient characteristics, interventions, and outcome in acute myocardial infarction complicated by cardiogenic shock (AMICS), due to predominantly right ventricular (RV) failure after revascularization, in comparison with patients suffering from left ventricular (LV) failure as these patients remain sparsely characterized. Methods and results From 2010 to 2017, consecutive AMICS patients admitted to either of two tertiary heart centres, covering 3.9 million citizens, corresponding to two-thirds of the Danish population, were identified and individually reviewed through patient records. A total of 1716 AMICS patients were identified, of which 1482 underwent acute revascularization and included for analysis. Hereof, 101 (7%) patients developed cardiogenic shock due to predominantly RV failure, while 1381 (93%) had significant LV involvement. Female sex was the only demographic factor associated with RV failure (35% vs. 25%, P = 0.01). Despite having a preserved LV ejection fraction, patients with predominantly RV failure were comparable to patients with LV involvement, in terms of haemodynamic and metabolic profile, here among variables commonly used in the cardiogenic shock definition including blood pressure (82 mmHg vs. 83 mmHg, P = 0.90) and lactate level (5.7 mmol/L vs. 5.4 mmol/L, P = 0.70). Patients with RV AMICS had significantly lower 30-day mortality than LV AMICS, and this result persisted after multivariable adjustment (RV vs. LV; hazard ratio 0.61, 95% confidence interval 0.41–0.92, P = 0.01). Conclusion In contemporary AMICS patients undergoing revascularization, patients with predominantly RV failure had comparable haemodynamics and metabolic derangement on admission compared to patients with LV failure but was associated with female sex and a significantly lower 30-day mortality.

Background Underlying plaque characteristics that lead to future revascularization during long-term follow-up remain poorly understood. Purpose We aimed to explore intracoronary imaging-derived measures as assessed by intravascular ultrasound (IVUS) and optical coherence tomography (OCT) associated with non-infarct related vessel revascularization (non-TVR) arising from imaged segments during long-term (up to 7 years) follow-up among patients with ST-elevated myocardial infarction (STEMI). Methods A total of 94 STEMI patients enrolled into the IBIS-4 (Integrated Biomarker Imaging Study-4) study undergoing serial (baseline and 13 months) IVUS and OCT in 2 non-infarct-related coronary arteries under high-intensity statin therapy were analyzed in the present study. Patients were divided into 2 groups according to the occurrence of non-TVR within previously imaged vessel segments (non-TVR: n=14, no non-TVR: n=80). Results Baseline characteristics including LDL level were comparable between groups. At baseline, lesions with future non-TVR were associated with greater percent atheroma volume by IVUS (55.6±5.4% vs. 49.6±6.1%, P Conclusion Greater plaque burden, smaller lumen area, and higher prevalence of OCT-detected fibroatheroma at baseline were associated with non-infarct related vessel revascularization. Lesions with non-TVR tend to have less-pronounced regression of coronary atheroma despite intensive statin therapy and achieved LDL levels. Non-TVR 7 years after index PCI Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation

Background Until 2009, aspirin and clopidogrel were recommended for most patients with acute coronary syndrome (ACS). After 2009, this recommendation was changed to aspirin combined with prasugrel or ticagrelor since randomised trials had demonstrated reduced cardiovascular mortality and ischemic events, however with a slight increase in bleeding risk. Randomised clinical trials often include selected patients and the results may not be generalisable to an all-comers population of high-risk ACS patients. Purpose To compare efficacy and safety of clopidogrel, ticagrelor, and prasugrel in all-comers patients with ST-segment elevation myocardial infarction (STEMI). Methods The Eastern Danish Heart Registry was utilised to identify all consecutive STEMI patients admitted to the capital region from 2009–2016. By individual linkage to Danish nationwide registries, claimed drug prescriptions and end points were obtained. Patients alive a week after discharge were included and stratified according to clopidogrel, ticagrelor, or prasugrel treatment, and followed for 18 months. The risk of the primary efficacy end point (a composite of all-cause mortality, recurrent myocardial infarction, and ischemic stroke) and the safety end point (bleeding events leading to hospital admission) were assessed by multivariate Cox proportional-hazard models. Results In total, 4841 STEMI patients were included (clopidogrel [n=1222], ticagrelor [n=1820], prasugrel [n=1799]). The median age was 66 (IQR 57–76) for clopidogrel, 64 (IQR 54–73) for ticagrelor, and 59 (IQR 51–67) for prasugrel, and only 19% were women of the prasugrel treated patients (29% for clopidogrel, 25% for ticagrelor). Treatment with anticoagulant therapy was 21% for clopidogrel treated patients (4% for ticagrelor, 5% for prasugrel). Number of events and incidence rates/100 years (IR) for the primary efficacy end point were 165 (IR 9.7) for clopidogrel, 134 (IR 5.1) for ticagrelor, and 107 (IR 4.1) for prasugrel, and for bleeding events 57 (IR 3.3) for clopidogrel, 60 (IR 2.3) for ticagrelor, and 55 (IR 2.1) for prasugrel treatment. Compared with clopidogrel, a reduction in the primary efficacy end point was found in patients treated with both ticagrelor (HR 0.47, 95% CI 0.36–0.63, p Conclusion Ticagrelor and prasugrel treatment in all-comers STEMI patients were associated with reduced rates of all-cause mortality and ischemic events without an increase in bleeding events when compared with clopidogrel treatment. No differences in efficacy or safety were found between prasugrel and ticagrelor treated patients. Efficacy+safety end points at 18 months Funding Acknowledgement Type of funding source: None

BACKGROUND: Identification of patients at high risk of non-cardiac mortality following ST-segment elevation myocardial infarction (STEMI) could guide clinicians to identify patients who require attention due to serious non-cardiac conditions after the acute phase of STEMI. The purpose of this study was to evaluate if the non-specific and prognostic biomarker of inflammation and comorbidity, soluble urokinase receptor (suPAR), could predict non-cardiac mortality in a cohort of STEMI patients.METHODS: SuPAR was measured in 1,190 STEMI patients who underwent primary percutaneous coronary intervention (pPCI). The primary endpoint was non-cardiac mortality, secondary endpoints were cardiac mortality, all-cause mortality, reinfarction and periprocedural acute kidney injury. Backwards elimination of potential confounders significantly associated with the respective outcome was used to adjust associations.RESULTS: Patients were followed for a median of 3.0 years (interquartile range 2.5 to 3.6 years). Multivariate cox regression revealed that a plasma suPAR level above 3.70 ng mL-1 was associated with non-cardiac and cardiac mortality at hazard ratios 3.33 (95 % confidence interval 1.67-6.63, p = 0.001, adjusted for age) and 0.99 (0.18-5.30, p = 0.98, adjusted for previous myocardial infarction and left ventricular ejection fraction), respectively.CONCLUSION: In patients with pPCI treated STEMI, suPAR was an independent prognostic biomarker of non-cardiac but not cardiac mortality and may identify patients with high risk of non-cardiac mortality.

Background Cardiogenic shock is the leading cause of death in patients with acute myocardial infarction, with short-term mortality of approximately 50%. Whether diabetes mellitus and high blood glucose levels are associated with mortality in contemporary patients with acute myocardial infarction complicated by cardiogenic shock is inadequately described. Purpose To investigate if diabetes mellitus and high admission blood glucose were associated with 30-day mortality in a large, contemporary population with acute myocardial infarction complicated by cardiogenic shock. Methods Patients with acute myocardial infarction complicated by cardiogenic shock admitted at two tertiary centres in Denmark from 2010 to 2017 were individually identified through patient charts, resulting in the inclusion of 1716 cardiogenic shock patients. Glucose level at admission to the intensive care unit was available in 1302 patients. Results There was no significant difference in 30-day mortality between diabetes mellitus types I and II (63% vs. 62%, NS). Thirty-day mortality was significantly higher in diabetes patients compared to non-diabetes patients (62% vs. 50%, P 16 mmol/L, 67%; P = 0.028) and non-diabetes patients (4–8 mmol/L, 32%; 8–12 mmol/L, 43%; 12–16 mmol/L, 57%; >16 mmol/l; 68%; P Conclusion Patients with acute myocardial infarction complicated by cardiogenic shock and concomitant diabetes mellitus type I or II had a significantly higher 30-day mortality in comparison to patients without diabetes mellitus, whereas no difference was found between diabetes mellitus types I and II. High glucose levels on admission to the intensive care unit were associated with increased 30-day mortality in diabetes mellitus and non-diabetes mellitus patients.

OBJECTIVES To ascertain the effect of age on outcomes after culprit-only and complete revascularization after Primary PCI (PPCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND The numbers of older patients being treated with PPCI are increasing. The optimal management of nonculprit stenoses in such patients is unclear. METHODS We conducted an analysis of patients aged ≥75 years randomized in the DANAMI-3-PRIMULTI study to either culprit-only or complete FFR-guided revascularization. The primary endpoint was a composite of all-cause mortality, nonfatal reinfarction, and ischaemia-driven revascularization of lesions in noninfarct-related arteries after a median of 27 months of follow-up. RESULTS One hundred and ten of six hundred and twenty seven patients in the DANAMI-3-PRIMULTI trial were aged ≥75 years. These patients were more likely female (p

Background Cardiac adipose tissue may have local paracrine effects on epicardial arteries and the underlying myocardium, promoting calcification and affecting myocardial microcirculation. We explored whether the total amount of cardiac adipose tissue was associated with coronary artery calcium score (CAC) and myocardial flow reserve in persons with type 1 or type 2 diabetes and healthy controls. Methods We studied three groups: (1) 30 controls, (2) 60 persons with type 1 diabetes and (3) 60 persons with type 2 diabetes. The three groups were matched for sex and age. The three groups derived from retrospective analysis of two clinical studies. All underwent cardiac 82Rb positron emission tomography/computed tomography (PET/CT) scanning. Cardiac adipose tissue volume (the sum of epicardial and pericardial fat), CAC, and myocardial flow reserve (ratio of pharmacological stress flow and rest flow) were evaluated using semiautomatic software. We applied linear regression to assess the association between cardiac adipose tissue, CAC and myocardial flow reserve. Results Mean (SD) cardiac adipose tissue volume was 99 (61) mL in the control group, 106 (78) mL in the type 1 diabetes group and 228 (97) mL in the type 2 diabetes group. Cardiac adipose tissue was positively associated with body mass index in all three groups (p ≤ 0.02). In the controls, cardiac adipose tissue was positively associated with CAC score (p = 0.008) and negatively associated with myocardial flow reserve (p = 0.005). However, cardiac adipose tissue was not associated with CAC or myocardial flow reserve in the groups including persons with type 1 or type 2 diabetes (p ≥ 0.50). Conclusions In contrast to what was found in healthy controls, we could not establish a relation between cardiac adipose tissue and coronary calcification or myocardial microvascular function in person with type 1 or type 2 diabetes. The role of cardiac adipose tissue in cardiovascular disease in diabetes remains unclear.

Background: Cardiogenic shock complicating ST-elevation myocardial infarction is characterised by progressive left ventricular dysfunction causing inflammation and neurohormonal activation. Often, cardiogenic shock develops after hospital admission. Whether inflammation and a neurohormonal activation precede development of clinical cardiogenic shock is unknown. Methods and results: In 93% of 2247 consecutive patients with suspected ST-elevation myocardial infarction admitted at two tertiary heart centres, admission plasma levels of pro-atrial natriuretic peptide, copeptin, mid-regional pro-adrenomedullin and stimulation-2 were measured on hospital admission. Patients were stratified according to no cardiogenic shock development and cardiogenic shock developed before (early cardiogenic shock) or after (late cardiogenic shock) leaving the catheterization laboratory. In total, 225 (10%) patients developed cardiogenic shock, amongst these patients late cardiogenic shock occurred in 64 (2.9%). All four biomarkers were independently associated with the development of late cardiogenic shock (odds ratio per two-fold increase in risk: 1.19–3.13) even when adjusted for the recently developed Observatoire Régional Breton sur l’Infarctus risk score for prediction of late cardiogenic shock development. Furthermore, pro-atrial natriuretic peptide, copeptin and mid-regional pro-adrenomedullin, but not stimulation-2, added significant predictive information, when added to the Observatoire Régional Breton sur l’Infarctus risk score (area under the receiver-operating characteristic curve, pro-atrial natriuretic peptide: 0.87, p=0.0008; copeptin: 0.86, p Conclusions: Pro-atrial natriuretic peptide, copeptin, mid-regional pro-adrenomedullin and stimulation-2 admission plasma concentration were associated with late cardiogenic shock development in patients admitted with suspected ST-elevation myocardial infarction. Pro-atrial natriuretic peptide, mid-regional pro-adrenomedullin and copeptin had independent predictive value for late cardiogenic shock development.