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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. 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. 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. 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. • Prasugrel and ticagrelor were associated with superior effectiveness compared with clopidogrel in all-comers with STEMI • No increase in bleedings leading to hospitalization were demonstrated for prasugrel and ticagrelor compared with clopidogrel • No differences in comparative effectiveness or safety were found between ticagrelor and prasugrel • This study questions the merits of prasugrel over ticagrelor in all-comers with STEMI despite its observational design [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Aims: To investigate seasonality and association of increased enterovirus and influenza activity in the community with ventricular fibrillation (VF) risk during first ST-elevation myocardial infarction (STEMI). Methods: This study comprised all consecutive patients with first STEMI (n = 4,659; aged 18–80 years) admitted to the invasive catheterization laboratory between 2010–2016, at Copenhagen University Hospital, Rigshospitalet, covering eastern Denmark (2.6 million inhabitants, 45% of the Danish population). Hospital admission, prescription, and vital status data were assessed using Danish nationwide registries. We utilized monthly/weekly surveillance data for enterovirus and influenza from the Danish National Microbiology Database (2010–2016) that receives copies of laboratory tests from all Danish departments of clinical microbiology. Results: Of the 4,659 consecutively enrolled STEMI patients, 581 (12%) had VF before primary percutaneous coronary intervention. In a subset (n = 807), we found that VF patients experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with the patients without VF (OR 3.39, 95% CI 1.76–6.54). During the study period, 2,704 individuals were diagnosed with enterovirus and 19,742 with influenza. No significant association between enterovirus and VF (OR 1.00, 95% CI 0.99–1.02), influenza and VF (OR 1.00, 95% CI 1.00–1.00), or week number and VF (p-value 0.94 for enterovirus and 0.89 for influenza) was found. Conclusion: We found no clear seasonality of VF during first STEMI. Even though VF patients had experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with patients without VF, no relationship was found between enterovirus or influenza exposure and occurrence of VF. [ABSTRACT FROM AUTHOR]

BACKGROUND The benefit of fractional flow reserve (FFR)--guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P=0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.) [ABSTRACT FROM AUTHOR]

The article focuses on trial of patients presenting with acute STsegment elevation myocardial infarction (STEMI), multivessel coronary artery disease. It mentions intermediate- sized trials have shown that complete revascularization is safe and reduces the risk of repeat revascularization and suggested that complete revascularization should be based on fractional flow reserve (FFR) measurements.

Background: Although some studies found improved coronary flow and myocardial salvage when stent implantation was deferred, the DANAMI-3-DEFER (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) did not show any improvement in clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) and deferred stenting.Objectives: This study sought to evaluate the effect of deferred stent implantation on infarct size, myocardial salvage, and microvascular obstruction (MVO) in patients with STEMI.Methods: In the present DANAMI-3 substudy, a total of 510 patients with STEMI were randomized to PCI with deferred versus immediate stent implantation. The patients underwent a cardiac magnetic resonance examination before discharge after the index procedure and again 3 months later. The primary endpoint was final infarct size.Results: Deferred stenting did not reduce final infarct size (9% left ventricle [LV]; interquartile range [IQR]: 3% to 18% vs. 10% LV; IQR: 3% to 18%; p = 0.67). Similarly, deferred stenting was not associated with myocardial salvage index (66%; IQR: 50% to 89% vs. 67%; IQR: 49% to 88%; p = 0.80) or presence of MVO (43% vs. 42%; p = 0.78). In a post hoc analysis, stent length was the only subgroup of 7 that had an effect on outcome. In patients with a stent length ≥24 mm, deferred stenting reduced the final infarct size (6% LV; IQR: 2% to 18% vs. 13% LV; IQR: 7% to 23%; p = 0.006; and p for interaction = 0.005).Conclusions: In the DANAMI-3-DEFER cardiac magnetic resonance substudy, routine deferred stenting did not reduce infarct size or MVO and did not increase myocardial salvage. These results do not support the use of routine deferred stenting in STEMI patients treated with primary PCI. (DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408). [ABSTRACT FROM AUTHOR]

Background Multislice computed tomography (MSCT) is a non-invasive, less expensive, low-radiation alternative to coronary angiography (CAG) prior to valvular heart surgery. MSCT has a high negative predictive value for coronary artery disease (CAD) but previous studies of patients with valvular disease have shown that MSCT, as the primary evaluation technique, lead to re-evaluation with CAG in about a third of cases and it is therefore not recommended. If a subgroup of patients with low- to intermediate risk of CAD could be identified and examined with MSCT, it could be cost-effective, reduce radiation and the risk of complications associated with CAG. Methods The study cohort was derived from a national registry of patients undergoing CAG prior to valvular heart surgery. Using logistic regression, we identified significant risk factors for CAD and developed a risk score (CT-valve score). The score was validated on a similar cohort of patients from another registry. Results The study cohort consisted of 2221 patients, 521 (23.5%) had CAD. The validation cohort consisted of 2575 patients, 771 (29.9%) had CAD. The identified risk factors were male sex, age, smoking, hyperlipidemia, hypertension, aortic valve disease, extracardiac arteriopathy, ejection fraction < 30% and diabetes mellitus. CT-valve score could identify a third of the population with a risk about 10%. Conclusion A score based on risk factors of CAD can identify patients that might benefit from using MSCT as a gatekeeper to CAG prior to heart valve surgery. [ABSTRACT FROM AUTHOR]

Background: Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only.Methods: We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularization of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933.Findings: From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularization guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0∙56, 95% CI 0∙38–0∙83; p=0∙004).Interpretation: In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints.Funding: Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research. [ABSTRACT FROM AUTHOR]

Background Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. Methods We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularisation of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933. Findings From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularisation guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0·56, 95% CI 0·38–0·83; p=0·004). Interpretation In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularisation should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. INSET: Research in context.. [ABSTRACT FROM AUTHOR]

Abstract: Background: Coronary CT angiography (CCTA) has become an important modality to evaluate the presence of coronary artery disease. Coronary artery stenosis of intermediate severity remains a therapeutic dilemma. Measurement of fractional flow reserve (FFR) during coronary angiography is the most established technique to determine the hemodynamic severity of a coronary artery lesion. The aim of this study was to compare CCTA with FFR. Methods: In 56 coronary artery stenoses (42 patients) we performed CCTA, quantitative coronary angiography and FFR. CCTA measurements included diameter stenosis (DS, %), area stenosis (AS, %), minimal lumen diameter (MLD, mm), minimal lumen area (MLA, mm2), lesion length (LL, mm), plaque volume (mm3) and burden (%). Results: FFR averaged 0.81±0.14, and 10 lesions had an abnormal FFR (<0.75). We found significant correlations between FFR and DS (r =−0.67, p <0.001), AS (r =−0.68, p <0.001), MLD (r =0.58, p <0.001), MLA (r =0.53, p <0.001), LL (r =−0.36, p =0.02), plaque volume (r =−0.36, p =0.02) and plaque burden (r =−0.59, p <0.001). By multivariate regression analysis AS and LL were the strongest determinants of an abnormal FFR. The optimal cut-off value for AS was >73% (sensitivity 90%, specificity 80%, negative predictive value 97%, and positive predictive value 50%) and for LL >10 mm (sensitivity 60% and specificity 49%). Conclusion: This study demonstrates that quantitative CCTA is correlated to FFR. Using our CCTA criteria of abnormality, significant coronary artery stenoses can be ruled out with a high negative predictive value. [ABSTRACT FROM AUTHOR]

Abstract: Glucagon-Like Peptide-1 (GLP-1) is an incretin peptide secreted from intestinal L-cells, whose potent plasma glucose-lowering action has prompted intense efforts to develop GLP-1 receptor-targeting drugs for treatment of diabetic hyperglycemia. More recently, GLP-1 and its analogues have been shown to exert cardiovascular effects in a number of experimental models. Here we tested exendin-4 (Exe-4), a peptide agonist at GLP-1 receptors, and GLP-1(9–36) amide, the primary endogenous metabolite of GLP-1 (both in the concentration range 0.03–3.0 nM), for their protective effects against ischemia–reperfusion injury (IRI) in an isolated rat heart preparation. When administered, the agents were only present for the first 15 min of a 120 min reperfusion period (postconditioning protocol). Exe-4, but not GLP-1(9–36) amide, showed a strong infarct-limiting action (from 33.2% ±2.7% to 14.5% ±2.2% of the ischemic area, p <0.05). This infarct size-limiting effect of Exe-4 was abolished by exendin(9–39) (Exe(9–39)), a GLP-1 receptor antagonist. In contrast, both Exe-4 and GLP-1(9–36) amide were able to augment left ventricular performance (left ventricular developed pressure and rate-pressure product) during the last 60 min of reperfusion. These effects were only partially antagonized by Exe(9–39). We suggest that Exe-4, in addition to being currently exploited in treatment of diabetes, may present a suitable candidate for postconditioning trials in clinical settings of IRI. The divergent agonist effects of Exe-4 and GLP-1(9–36), along with correspondingly divergent antagonistic efficacy of Exe(9–39), seem consistent with the presence of more than one type of GLP-1 receptor in this system. [Copyright &y& Elsevier]

Third-degree atrioventricular block after acute myocardial infarction is considered to have prognostic importance. However, its importance in conjunction with thrombolytic therapy and its relation to left ventricular function remains uncertain. This report also outlines an important distinction between atrioventricular block in the setting of anterior and inferior wall acute myocardial infarction, with profound clinical and prognostic implications. [Copyright &y& Elsevier]

Introduction: Elderly patients with acute coronary syndrome (ACS) have a higher risk of adverse cardiovascular events and may be frail but are underrepresented in clinical trials. Previous studies have proposed that frailty assessment is a better tool than chronological age, in assessing older patients' biological age, and may exceed conventional risk scores in predicting the prognosis. Therefore, we wanted to investigate the prevalence and impact on 12-month outcomes of frailty in patients ≥70 years with ACS referred for coronary angiography (CAG). Methods: Patients ≥70 years with ACS referred for CAG underwent frailty scoring with the clinical frailty scale (CFS). Patients were divided into three groups depending on their CFS: robust (1–3), vulnerable (4), and frail (5–9) and followed for 12 months. Results: Of 455 patients, 69 (15%) patients were frail, 79 (17%) were vulnerable, and 307 (68%) were robust. Frail patients were older (frail: 80.9 ± 5.7 years, vulnerable: 78.5 ± 5.5 years, and robust: 76.6 ± 4.9 years, p < 0.001) and less often treated with percutaneous coronary intervention (frail: 56.5%, vulnerable: 53.2%, and robust: 68.6%, p = 0.014). 12-month mortality was higher among frail patients (frail: 24.6%, vulnerable: 21.8%, and robust: 6.2%, p < 0.001). Frailty was associated with a higher mortality after adjustment for age, sex, comorbidities, the Global Registry of Acute Coronary Events (GRACE) score, and revascularisation (HR 2.67, 95% CI 1.30–5.50, p = 0.008). There was no difference between GRACE and CFS in predicting 12-month mortality (p = 0.893). Conclusions: Fifteen percent of patients ≥70 years old with ACS referred for CAG are frail. Frail patients have significantly higher 12-month mortality. GRACE and CFS are similar in predicting 12-month mortality. [ABSTRACT FROM AUTHOR]

Background: Inflammation in ST-segment elevation myocardial infarction (STEMI) is an important contributor to both acute myocardial ischemia and reperfusion injury after primary percutaneous coronary intervention (PCI). Methylprednisolone is a glucocorticoid with potent anti-inflammatory properties with an acute effect and is used as an effective and safe treatment of a wide range of acute diseases. The trial aims to investigate the cardioprotective effects of pulse-dose methylprednisolone administered in the pre-hospital setting in patients with STEMI transferred for primary PCI. Methods: This trial is a randomized, blinded, placebo-controlled prospective clinical phase II trial. Inclusion will continue until 378 patients with STEMI have been evaluated for the primary endpoint. Patients will be randomized 1:1 to a bolus of 250 mg methylprednisolone intravenous or matching placebo over a period of 5 min in the pre-hospital setting. All patients with STEMI transferred for primary PCI at Rigshospitalet, Copenhagen University Hospital, Denmark, will be screened for eligibility. The main eligibility criteria are age ≥ 18 years, acute onset of chest pain with < 12 h duration, STEMI on electrocardiogram, no known allergy to glucocorticoids or no previous coronary artery bypass grafting, previous acute myocardial infarction in assumed culprit, or a history with previous maniac/psychotic episodes. Primary outcome is final infarct size measured by late gadolinium enhancement on cardiac magnetic resonance (CMR) 3 months after STEMI. Secondary outcomes comprise key CMR efficacy parameters, clinical endpoints at 3 months, the peak of cardiac biomarkers, and safety. Discussion: We hypothesize that pulse-dose methylprednisolone administrated in the pre-hospital setting decreases inflammation and thus reduces final infarct size in patients with STEMI treated with primary PCI. Trial registration: EU-CT number: 2022–500762-10–00; Submitted May 5, 2022. ClinicalTrials.gov Identifier: NCT05462730; Submitted July 7, 2022, first posted July 18, 2022. [ABSTRACT FROM AUTHOR]

Influenza vaccination reduces the risk of adverse cardiovascular events. The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. The cumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion, there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccination but regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Introduction: Prediction of recurrent ventricular arrhythmia (VA) in survivors of an out‐of‐hospital cardiac arrest (OHCA) is important, but currently difficult. Risk of recurrence may be related to presence of myocardial scarring assessed with late gadolinium enhancement cardiac magnetic resonance (LGE‐CMR). Our study aims to characterize myocardial scarring as defined by LGE‐CMR in survivors of a VA‐OHCA and investigate its potential role in the risk of new VA events. Methods: Between 2015 and 2022, a total of 230 VA‐OHCA patients without ST‐segment elevation myocardial infarction had CMR before implantable cardioverter‐defibrillator implantation for secondary prevention at Copenhagen University Hospital, Rigshospitalet, and Hospital Clínic, University of Barcelona, of which n = 170 patients had a conventional (no LGE protocol) CMR and n = 60 patients had LGE‐CMR (including LGE protocol). Scar tissue including core, border zone (BZ) and BZ channels were automatically detected by specialized investigational software in patients with LGE‐CMR. The primary endpoint was recurrent VA. Results: After exclusion, n = 52 VA‐OHCA patients with LGE‐CMR and a mean left ventricular ejection fraction of 49 ± 16% were included, of which 18 (32%) patients reached the primary endpoint of VA. Patients with recurrent VA in exhibited greater scar mass, core mass, BZ mass, and presence of BZ channels compared with patients without recurrent VA. The presence of BZ channels identified patients with recurrent VA with 67% sensitivity and 85% specificity (area under the ROC curve (AUC) 0.76; 95% CI: 0.63–0.89; p <.001) and was the strongest predictor of the primary endpoint. Conclusions: The presence of BZ channels was the strongest predictor of recurrent VA in patients with an out of‐hospital cardiac arrest and LGE‐CMR. [ABSTRACT FROM AUTHOR]

The frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. This study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. Overall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: −27.1 mg/dL; 95% CI: −37.7 to −16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). Triple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844) [Display omitted] [ABSTRACT FROM AUTHOR]

BACKGROUND: The impact of disease severity on the outcome after complete revascularization in patients with ST-segment--elevation myocardial infarction and multivessel disease is uncertain. The objective of this post hoc study was to evaluate the impact of number of diseased vessel, lesion location, and severity of the noninfarct-related stenosis on the effect of fractional flow reserve--guided complete revascularization. METHODS AND RESULTS: In the DANAMI-3-PRIMULTI study (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization), we randomized 627 ST-segment--elevation myocardial infarction patients to fractional flow reserve--guided complete revascularization or infarct-related percutaneous coronary intervention only. In patients with 3-vessel disease, fractional flow reserve--guided complete revascularization reduced the primary end point (all-cause mortality, reinfarction, and ischemia-driven revascularization; hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.17--0.64; P=0.001), with no significant effect in patients with 2-vessel disease (HR, 0.77; 95% CI, 0.47--1.26; P=0.29; P for interaction =0.046). A similar effect was observed in patients with diameter stenosis ≥90% of noninfarct-related arteries (HR, 0.32; 95% CI, 0.18-- 0.62; P=0.001), but not in patients with less severe lesions (HR, 0.72; 95% CI, 0.44--1.19; P=0.21; P for interaction =0.06). The effect was most pronounced in patients with 3-vessel disease and noninfarct-related stenoses ≥90%, and in this subgroup, there was a nonsignificant reduction in the end point of mortality and reinfarction (HR, 0.32; 95% CI, 0.08--1.32; P=0.09). Proximal versus distal location did not influence the benefit from complete revascularization. CONCLUSIONS: The benefit from fractional flow reserve--guided complete revascularization in ST-segment--elevation myocardial infarction patients with multivessel disease was dependent on the presence of 3-vessel disease and noninfarct diameter stenosis ≥90% and was particularly pronounced in patients with both of these angiographic characteristics. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01960933. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content. Methods: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion–related MACEs and high-risk plaque characteristics. Results: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14–3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12–12.77)]) and nonculprit lesion–related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25–6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P =0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P =0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P =0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P =0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21–5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86–1.69]). Conclusions: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02171065. [ABSTRACT FROM AUTHOR]

Background Vascular access complications after coronary angiography (CAG) and percutaneous coronary intervention (PCI) are known to increase morbidity, prolong hospitalization and raise hospital costs. Therefore, risk factor identification and improvement of safety strategies for vascular management are important. We aimed to assess the incidence of major vascular complications related to femoral access, and to identify potential risk factors. Methods Over a period of six years, 23,870 index procedures (CAG) were performed in two centres, prospectively entered in the database and retrospectively analysed. Data was obtained from the Eastern Danish Heart Registry and cross-matched with data from the Danish Vascular Registry. Index procedures were defined as the first trans-femoral procedure. Demographic, procedural and mortality data, as well as information on access complications requiring surgery within 30 days were collected. Mortality data were collected for minimum 12 months. Results We identified 130 (0.54%) access complications requiring surgery; 65 pseudoaneurysms (0.28%), 46 arterial occlusions (0.19%), 15 hematomas (nine groin and six retroperitoneal hematomas) (0.06%), and 4 arterial dissections (0.02%). Risk factors for complications were left sided femoral access (OR 4.11 [2.29–7.37] p < 0.001), peripheral arterial disease (PAD) (OR 2.42 [1.48–3.94] p < 0.0001) and female sex (OR 2.22 [1.51–3.24] p < 0.0001). Conclusion Vascular complications related to femoral access in coronary diagnostic and interventional procedures are low (0.54%). Risk factors were left sided access, PAD, and female sex. [ABSTRACT FROM AUTHOR]

To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF. Using Danish nationwide registry data (1978–2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. We identified 55,110 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.59 (95%CI 2.29–2.93). The estimate was higher among siblings (SIR 6.67 [95%CI 4.69–9.48]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 7.23 [95%CI 5.40–9.68]) and having >1 proband (SIR of 5.28 [95%CI 2.75–10.14]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (13.17 [95%CI 8.90–19.49]. A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. The relative rate was increased when the proband was diagnosed at a young age. These data suggest that screening families of unexplained HF with onset below 50 years is indicated. • A family history of unexplained HF was associated with a 2 fold increased rate of unexplained HF among first-degree relatives. • These data suggest that screening families of unexplained HF with onset <50 years is indicated. [ABSTRACT FROM AUTHOR]

The effects of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on endothelial function as assessed by flow-mediated dilation (FMD) in patients with acute myocardial infarction (AMI) are unknown. Therefore, we aimed to investigate the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD, and its association with coronary atherosclerosis in non-infarct related arteries using intracoronary intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT). This was a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial, which compared the effects of biweekly alirocumab 150 mg vs. placebo added to rosuvastatin. Brachial artery FMD was measured at 4 and 52 weeks, and intracoronary imaging at baseline and 52 weeks. 139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = −0.21%, 95% CI −0.77 to 0.35, p = 0.47). FMD improved throughout 52 weeks in both groups similarly (p < 0.001). There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = −1.00, p = 0.006), but not with lipid pool (NIRS) (n = 139, slope = −7.36, p = 0.32), or fibrous cap thickness (OCT) (n = 81, slope = −1.57, p = 0.62). Among patients with AMI, the addition of alirocumab did not result in further improvement of FMD as compared to 52 weeks secondary preventative medical therapy including high-intensity statin therapy. FMD was significantly associated with coronary plaque burden at baseline, but not with lipid pool or fibrous cap thickness. [Display omitted] • This randomized trial assessed the effect of alirocumab/statin vs. placebo/statin on flow mediated dilation (FMD) in acute myocardial infarction (AMI). • FMD improved throughout 1 year after AMI with medical therapy similarly in alirocumab/statin vs. placebo/statin treated patients. • FMD at baseline was significantly inversely associated with coronary plaque burden on intravascular ultrasound. [ABSTRACT FROM AUTHOR]

Abstract: Aim: GLP-1(7–36)amide (GLP-1) is an intestinal hormone with effects on glucose metabolism and feeding behavior, including insulinotropic, insulinomimetic, glucagonostatic and anorectic actions. In experimental settings, GLP-1 has also been shown to diminish infarct size following heart ischemia-reperfusion. GLP-1 analogs with extended half-lives are continuously being developed against type 2 diabetes mellitus. Of these, only exendin-4 (exenatide, registered as Byetta) has been shown to mimic the infarct size-limiting effect of GLP-1 in a clinically relevant application as a postconditioning agent. The aim of this work was to test, in a postconditioning mode, a novel, proteolysis-resistant GLP-1 analog N-Ac-GLP-1(7–34)amide, herein termed curaglutide, for its cardioprotective ability. Method: Global ischemia (35min)-reperfusion (120min) was applied in isolated, retrogradely perfused rat hearts. Peptides were present for 15min at the onset of reperfusion. Cardiac function parameters (beats per minute, left ventricle developed and diastolic pressures, rate-pressure product) were measured. Infarct size was determined by 2,3,5-tripehyltetrazolium chloride staining and planimetry. Results: Curaglutide did not affect any of the functional heart parameters when administered without preceding ischemia. Curaglutide 0.3nM diminished significantly the postischemic hypercontracture, with no significant effect on the left ventricle developed pressure or rate-pressure product. Infarct size was reduced by curaglutide postconditioning from 24.8% (SEM 2.8, N=14) to 11.4% (SEM 3.2, N=8; P<0.05). These effects of curaglutide on postischemic hypercontracture and infarct size were similar in magnitude to corresponding effects of GLP-1 receptor agonist exendin-4. The cardioprotective effects of both agents were abolished in the presence of a GLP-1 receptor antagonist exendin(9–39). Conclusion: Curaglutide is a new, proteolysis-resistant GLP-1 analog with a beneficial effect on reperfusion-injury in an isolated rat heart. Curaglutide was here shown to act through GLP-1 receptors. Based on the present results, more extensive experimental studies in vivo, comparing dose–response characteristics and efficacy of curaglutide and exendin-4 appear warranted. [Copyright &y& Elsevier]

Recent experimental data suggest glucagon-like peptide 1 (GLP-1) and its analogs to have direct effects on the cardiovascular system, in addition to their classic glucoregulatory actions. These direct effects may be cardioprotective, contractility augmenting, and vasorelaxant. A few preliminary clinical trials appear to support a mechanical function improvement after GLP-1 administration to patients with a weakened left ventricle. Based on animal studies, diminished lethal injury to the postischemic reperfused myocardium appears to be a particularly promising prospect, awaiting to be tested in clinical settings. [Copyright &y& Elsevier]

Abstract: GLP-1 and its metabolite GLP-1(9–36)a have been shown to exert cardiotropic effects, and were demonstrated to be cardioprotective agents in isolated, postischemic rat or mouse hearts. An agent''s total effect on myocardial performance in a postconditioning paradigm is a sum of its myocyte-preserving (cardioprotective) and contractility-affecting (negative or positive inotropic) action components. These components may not always be explicitly separated by the experimental protocol. We propose an analytical approach to identify and quantify the cardioprotective and inotropic components in a postconditioning protocol, as exemplified by use of GLP-1 and GLP-1(9–36)a following a global ischemia in isolated rat hearts. Peptides were administered during the first 15min of 120min reperfusion. GLP-1 0.3nM reduced infarct size from 23.2±2.4% to 14.1±2.3% of area-at-risk (n =15, P =0.0223), an effect abolished by the GLP-1 receptor antagonist, exendin(9–39) 5nM. GLP-1 showed only a small, non-significant tendency to increase mechanical performance (increase of LVDP by 26.7%, P =0.1621; RPP 33.5%, P =0.0858; dP/dt max 28.5%, P =0.1609). This could be accounted for by the cardioprotective component of GLP-1 action, rather than any true inotropic effect. In contrast, GLP-1(9–36)a did not reduce infarct size significantly, but acted as a strong negative inotrope in postischemic hearts, causing a contractility deficit (LVDP 58.8%, P =0.0004; RPP 58.2%, P =0.0007; dP/dt max =58.2%, P =0.0012), quantifiable by an analysis of infarct size-mechanical performance plots. These results help resolve certain apparent discrepancies between some of the published effects of GLP-1 and GLP-1(9–36)a. [Copyright &y& Elsevier]

The selective thrombin inhibitor bivalirudin with a provisional glycoprotein IIb/IIIa inhibitor (GPI) has been shown to be comparable to heparin plus GPI in the rates of ischemic events but to significantly reduce the risk of bleeding complications in patients with acute coronary syndromes. The aim of this preliminary study was to describe the feasibility and safety of a switch from prehospital administration of unfractionated heparin to bivalirudin in ST-elevation acute myocardial infarction (STEMI) patients referred for primary percutaneous coronary intervention. Patients with STEMI treated with a 1-mg/kg bivalirudin bolus in the ambulance followed by infusion during angiography/primary percutaneous coronary intervention were compared with a STEMI control group (from the preceding year) treated with 10,000 U unfractionated heparin in the ambulance followed by in-hospital treatment with a GPI. A total of 102 patients (59%) receiving bivalirudin and 72 receiving heparin were followed during hospitalization. The baseline characteristics and prehospital treatment times were comparable between the 2 groups. The thrombolysis in myocardial infarction flow before and after primary percutaneous coronary intervention was similar. Stents were used significantly more often in the heparin-treated patients (90% versus 76%; p = 0.04), with bailout GPI for those receiving bivalirudin occurring in 30% compared with 83% of those receiving heparin (p <0.001). Significant bleeding complications were seen in <10% of all patients undergoing angiography with no difference between groups. Bivalirudin was easy to administer in the prehospital setting and did not affect the prehospital run times. In conclusion, the results suggest that prehospital bivalirudin administration is as safe and effective as heparin in the treatment of patients with STEMI. Prehospital administration seemed to reduce the need for GPI. [Copyright &y& Elsevier]

The effect of limb remote ischaemic conditioning (RIC) on myocardial infarct (MI) size and left ventricular ejection fraction (LVEF) was investigated in a pre-planned cardiovascular magnetic resonance (CMR) substudy of the CONDI-2/ERIC-PPCI trial. This single-blind multi-centre trial (7 sites in UK and Denmark) included 169 ST-segment elevation myocardial infarction (STEMI) patients who were already randomised to either control (n = 89) or limb RIC (n = 80) (4 × 5 min cycles of arm cuff inflations/deflations) prior to primary percutaneous coronary intervention. CMR was performed acutely and at 6 months. The primary endpoint was MI size on the 6 month CMR scan, expressed as median and interquartile range. In 110 patients with 6-month CMR data, limb RIC did not reduce MI size [RIC: 13.0 (5.1-17.1)% of LV mass; control: 11.1 (7.0-17.8)% of LV mass, P = 0.39], or LVEF, when compared to control. In 162 patients with acute CMR data, limb RIC had no effect on acute MI size, microvascular obstruction and LVEF when compared to control. In a subgroup of anterior STEMI patients, RIC was associated with lower incidence of microvascular obstruction and higher LVEF on the acute scan when compared with control, but this was not associated with an improvement in LVEF at 6 months. In summary, in this pre-planned CMR substudy of the CONDI-2/ERIC-PPCI trial, there was no evidence that limb RIC reduced MI size or improved LVEF at 6 months by CMR, findings which are consistent with the neutral effects of limb RIC on clinical outcomes reported in the main CONDI-2/ERIC-PPCI trial. [ABSTRACT FROM AUTHOR]

As part of normal ageing, conductance arteries lose their cushion function, left ventricle (LV) filling and also left atrial emptying are impaired. The relation between conductance artery stiffness and LV diastolic function is normally explained by arterial hypertension and LV hypertrophy as needed intermediaries. We examined whether age-related aortic stiffening may influence LV diastolic function in normal healthy subjects. Aortic distensibility and pulse wave velocity (PWV) were related to LV emptying and filling parameters and left atrial emptying parameters as determined by magnetic resonance imaging in 36 healthy young (< 35 years) and 16 healthy middle-aged and elderly (> 35 years) with normal arterial blood pressure and myocardial mass. In the overall cohort, total aorta PWV correlated to a decrease in LV peak-emptying volume (r = 0.43), LV peak-filling (r = 0.47), passive atrial emptying volume (r = 0.66), and an increase in active atrial emptying volume (r = 0.47) (all p < 0.001). PWV was correlated to passive atrial emptying volume even if only the > 35-year-old were considered (r = 0.53; p < 0.001). Total peripheral resistance demonstrated similar correlations as PWV, but in a regression analysis only the total aorta PWV was related to left atrial (LA) passive emptying volume. Via impaired ventriculo-arterial coupling, the increased aortic PWV seen with normal ageing hence affects atrio-ventricular coupling, before increased aortic PWV is associated with significantly increased arterial blood pressure or LV hypertrophic remodelling. Our findings reinforce the existence of atrio-ventriculo-arterial coupling and suggest aortic distensibility should be considered an early therapeutic target to avoid diastolic dysfunction of the LV. [ABSTRACT FROM AUTHOR]

Aims: Insulin resistance associates with development of metabolic syndrome and risk of cardiovascular disease. The link between insulin resistance and cardiovascular disease is complex and multifactorial. Confirming the genetic link between insulin resistance, type 2 diabetes, and coronary artery disease, as well as the extent of coronary artery disease, is important and may provide better risk stratification for patients at risk. We investigated whether a genetic risk score of 53 single nucleotide polymorphisms known to be associated with insulin resistance phenotypes was associated with diabetes and burden of coronary artery disease. Methods and results: We genotyped patients with a coronary angiography performed in the capital region of Denmark from 2010–2014 and constructed a genetic risk score of the 53 single nucleotide polymorphisms. Logistic regression using quartiles of the genetic risk score was performed to determine associations with diabetes and coronary artery disease. Associations with the extent of coronary artery disease, defined as one-, two- or three-vessel coronary artery disease, was determined by multinomial logistic regression. We identified 4,963 patients, of which 17% had diabetes and 55% had significant coronary artery disease. Of the latter, 27%, 14% and 14% had one, two or three-vessel coronary artery disease, respectively. No significant increased risk of diabetes was identified comparing the highest genetic risk score quartile with the lowest. An increased risk of coronary artery disease was found for patients with the highest genetic risk score quartile in both unadjusted and adjusted analyses, OR 1.21 (95% CI: 1.03, 1.42, p = 0.02) and 1.25 (95% CI 1.06, 1.48, p<0.01), respectively. In the adjusted multinomial logistic regression, patients in the highest genetic risk score quartile were more likely to develop three-vessel coronary artery disease compared with patients in the lowest genetic risk score quartile, OR 1.41 (95% CI: 1.10, 1.82, p<0.01). Conclusions: Among patients referred for coronary angiography, only a strong genetic predisposition to insulin resistance was associated with risk of coronary artery disease and with a greater disease burden. [ABSTRACT FROM AUTHOR]

Introduction: The predictors of stent treatment failure and their importance 10 years after treatment with drug-eluting stents (DESs) have not been reported in detail. Methods: Data were retrieved from the SORT-OUT II database encompassing 2,849 non-left main coronary lesions in 2,073 unselected all-comer patients treated with first-generation DES and followed clinically for 10 years. Stent treatment failure (STF) was defined as definite or probable stent thrombosis, target lesion revascularization (TLR), or >70% restenosis left untreated. Target lesion failure (TLF) was defined as cardiac death, target vessel myocardial infarction, or TLR. Characteristics predicting higher hazard ratios (HRs) were identified by the multivariate Cox regression analysis. Results: A stent diameter ≤2.5 versus ≥3.5 mm had STF 23.3 versus 11.8% and TLF 27.9 versus 18.8%. Stent length <20 versus >40 mm had STF 13.0 versus 29.0% and TLF 18.7 versus 34.6%. In multivariate analysis, decreasing stent diameter (HR: 1.24 [3.0 mm] to 2.12 [2.25 mm], reference ≥3.5 mm) and increasing stent length (HR: 1.15 [20–30 mm] to 2.07 [>40 mm], reference <20 mm) predicted STF together with diabetes (HR: 1.31), previous revascularization (HR: 1.31), restenotic (HR: 2.25), bifurcation (HR: 1.45), and chronically occluded lesions (HR: 1.54). A predictive score (PS) was calculated for each lesion from the HRs for the predictors present. The 10-year rates of STF were 10% in lesions with a PS ≤ 1.5 and 37% in those with PS ≥ 3.5. Conclusions: Ten-year outcomes show large variations depending on the stent size and a few patient and lesion characteristics. The calculation of a PS from these unambiguous variables may be used to improve the risk estimate in individual lesions and patients. [ABSTRACT FROM AUTHOR]

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%, 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).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.Funding: Abbott Vascular, Infraredx, and The Medicines Company. [ABSTRACT FROM AUTHOR]

Background: Noninvasive screening for cardiac allograft vasculopathy (CAV) instead of invasive coronary angiography (ICA) within the first 3 to 5 years after heart transplantation (HTx) is controversial. We evaluated a strategy of intravascular ultrasound (IVUS)–guided conversion to early noninvasive screening post‐HTx. Methods: A single‐center study of 103 consecutive HTx recipients from 2008 to 2018 undergoing ICA at 1 year post‐HTx. Of 88 patients with normal 1‐year ICA, sixty‐six patients underwent IVUS examination for risk stratification by maximal intimal thickness (MIT) into (i) low‐risk group (MIT < 0.5 mm) (n = 41, 62%) followed noninvasively versus (ii) high‐risk group (MIT ≥ 0.5 mm) (n = 25, 38%) followed with yearly ICA. Both groups underwent ICA at year 5 post‐HTx. We evaluated a combined endpoint of angiographic CAV and death at 5‐year follow‐up post‐HTx. Results: Median (IQR) age was 51 (33–60) years, and 62% were male. Follow‐up was 1443 (1125–1456) days. Survival free from angiographic CAV (Kaplan‐Meier) differed significantly between groups (log‐rank p <.0001). A subgroup of 27 patients completed ICA at year 5, and the proportion of angiographic CAV was significantly lower in low‐risk patients (p <.0001). Conclusion: IVUS‐guided selection for early noninvasive CAV screening appears to be safe and holds promise as a novel strategy for early risk stratification and CAV surveillance post‐HTx. [ABSTRACT FROM AUTHOR]

Background: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild.Objectives: This study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non-flow-limiting vulnerable plaques.Methods: Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically nonobstructive stenosis not intended for PCI but with IVUS plaque burden of ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) versus GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (nonpowered) safety endpoint was randomized target lesion failure (cardiac death, target vessel-related MI, or clinically driven target lesion revascularization) at 24 months. The secondary (nonpowered) clinical effectiveness endpoint was randomized lesion-related major adverse cardiac events (cardiac death, MI, unstable angina, or progressive angina) at latest follow-up.Results: A total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by near-infrared spectroscopy-IVUS, the median plaque burden was 73.7%, the median MLA was 2.9 mm2, and the median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and the median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9 ± 2.6 mm2 compared with 3.0 ± 1.0 mm2 in GDMT alone-treated lesions (least square means difference: 3.9 mm2; 95% confidence interval: 3.3 to 4.5; p < 0.0001). Target lesion failure at 24 months occurred in similar rates of BVS-treated and GDMT alone-treated patients (4.3% vs. 4.5%; p = 0.96). Randomized lesion-related major adverse cardiac events occurred in 4.3% of BVS-treated patients versus 10.7% of GDMT alone-treated patients (odds ratio: 0.38; 95% confidence interval: 0.11 to 1.28; p = 0.12).Conclusions: PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA, and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial. (PROSPECT ABSORB [Providing Regional Observations to Study Predictors of Events in the Coronary Tree II Combined with a Randomized, Controlled, Intervention Trial]; NCT02171065). [ABSTRACT FROM AUTHOR]

Abstract: Transcatheter aortic valve implantation is a new and rapidly evolving treatment option for high-risk surgical patients with degenerative aortic valve stenosis. Long-term results with these new valve prostheses are lacking, and potential valve dysfunction and failure would require valve replacement. We report the first case of surgical valve replacement in a patient with a dysfunctional transcatheter-implanted aortic valve prosthesis 4 months after implantation. [Copyright &y& Elsevier]

Treatment with newer direct-acting anti-platelet drugs (Ticagrelor and Prasugrel) prior to primary percutaneous coronary intervention (PCI) is associated with improved outcome in patients with ST-segment elevation myocardial infarction (STEMI) when compared with Clopidogrel. We compared infarct size following treatment with Ticagrelor/Prasugrel versus Clopidogrel in the DANish trial in Acute Myocardial Infarction (DANAMI-3) population of STEMI patients treated with primary PCI. Patients were loaded with Clopidogrel, Ticagrelor or Prasugrel in the ambulance before primary PCI. Infarct size and myocardial salvage index were calculated using cardiac magnetic resonance (CMR) during index admission and at three-month follow-up. Six-hundred-and-ninety-three patients were included in this analysis. Clopidogrel was given to 351 patients and Ticagrelor/Prasugrel to 342 patients. The groups were generally comparable in terms of baseline and procedural characteristics. Median infarct size at three-month follow-up was 12.9% vs 10.0%, in patients treated with Clopidogrel and Ticagrelor/ Prasugrel respectively (p < 0.001), and myocardial salvage index was 66% vs 71% (p < 0.001). Results remained significant in a multiple regression model (p < 0.001). Pre-hospital loading with Ticagrelor or Prasugrel compared to Clopidogrel, was associated with smaller infarct size and larger myocardial salvage index at three-month follow-up in patients with STEMI treated with primary PCI. • Newer P2Y 12 antagonists are superior to Clopidogrel in terms of clinical outcomes in patients with acute coronary syndromes. • The mechanism of action mediating this difference is unclear. • A plausible mechanistic explanation could involve a decrease in final infarct size. [ABSTRACT FROM AUTHOR]

Objective: We aimed to relate the amount of jeopardized myocardium to mortality in shocked patients presenting to the catheterization laboratory with ST-elevation myocardial infarction (STEMI) and cardiogenic shock.Background: In contrast with historical data and previous professional guidance, contemporary randomized data suggest that multi-vessel revascularization in such patients does not improve survival; mechanistic insight is incomplete.Methods: Clinical databases identified cases of STEMI and shock triaged for primary percutaneous coronary intervention (PPCI) in Eastern Denmark from June 2011 to December 2014 (n = 128). British Cardiovascular Intervention Society (BCIS)-1 jeopardy scores were calculated from angiography. The study endpoint was 30-day mortality.Results: Median lactate values were 6.0 [2.9-10.7] mmol/L. 30-day mortality was 53.9%. 68% of patients had multi-vessel coronary disease. Median pre-PCI BCIS-1 myocardial jeopardy scores were 8 [6-10]. After multiple logistic regression increasing age (p = 0.008; odds ratio [OR] 1.06), lactate values (p = 0.017; OR 1.02), mechanical ventilation (p = 0.011; OR 1.25) and a systolic blood pressure ≤ 90 mmHg at end-case (p = 0.005; OR 1.26) were predictive of 30-day mortality. Post-PPCI culprit vessel TIMI 3 flow was associated with reduced mortality (p < 0.001; OR 0.66). There was no association between pre-PCI jeopardy scores and the primary endpoint.Conclusions: In patients with STEMI and shock, myocardial jeopardy scores do not relate to patient outcomes. Jeopardy scores may be applied to existing datasets in order to understand why multi-vessel revascularization does not lead to the anticipated clinical benefits in cardiogenic shock. [ABSTRACT FROM AUTHOR]

• SuPAR was a strong prognostic biomarker of non-cardiac mortality after STEMI. • The suPAR level was independent of sampling time < 12 h after revascularization. • SuPAR may identify patients in risk of non-cardiac mortality prior to discharge. 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. 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. Patients were followed for a median of 3.0 years (interquartile range 2.5– 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. 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. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD.Methods: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale.Results: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type.Conclusions: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women.Trial Registration: Clinicaltrials.gov, NCT02400229. [ABSTRACT FROM AUTHOR]

Objective: To implement detailed EU cardiac computed tomography angiography (CCTA) quality criteria in the multicentre DISCHARGE trial (FP72007-2013, EC-GA 603266), we reviewed image quality and adherence to CCTA protocol and to the recommendations of invasive coronary angiography (ICA) in a pilot study.Materials and Methods: From every clinical centre, imaging datasets of three patients per arm were assessed for adherence to the inclusion/exclusion criteria of the pilot study, predefined standards for the CCTA protocol and ICA recommendations, image quality and non-diagnostic (NDX) rate. These parameters were compared via multinomial regression and ANOVA. If a site did not reach the minimum quality level, additional datasets had to be sent before entering into the final accepted database (FADB).Results: We analysed 226 cases (150 CCTA/76 ICA). The inclusion/exclusion criteria were not met by 6 of the 226 (2.7%) datasets. The predefined standard was not met by 13 of 76 ICA datasets (17.1%). This percentage decreased between the initial CCTA database and the FADB (multinomial regression, 53 of 70 vs 17 of 75 [76%] vs [23%]). The signal-to-noise ratio and contrast-to-noise ratio of the FADB did not improve significantly (ANOVA, p = 0.20; p = 0.09). The CTA NDX rate was reduced, but not significantly (initial CCTA database 15 of 70 [21.4%]) and FADB 9 of 75 [12%]; p = 0.13).Conclusion: We were able to increase conformity to the inclusion/exclusion criteria and CCTA protocol, improve image quality and decrease the CCTA NDX rate by implementing EU CCTA quality criteria and ICA recommendations.Key Points: • Failure to meet protocol adherence in cardiac CTA was high in the pilot study (77.6%). • Image quality varies between sites and can be improved by feedback given by the core lab. • Conformance with new EU cardiac CT quality criteria might render cardiac CTA findings more consistent and comparable. [ABSTRACT FROM AUTHOR]

Background: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI.Methods: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI.Results: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710).Conclusions: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: For patients with severe aortic stenosis and coronary artery disease, the completely percutaneous approach to aortic valve replacement and revascularization has not been compared with the standard surgical approach. Methods: The prospective SURTAVI trial (Safety and Efficiency Study of the Medtronic CoreValve System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement) enrolled intermediate-risk patients with severe aortic stenosis from 87 centers in the United States, Canada, and Europe between June 2012 and June 2016. Complex coronary artery disease with SYNTAX score (Synergy Between PCI with Taxus and Cardiac Surgery Trial) >22 was an exclusion criterion. Patients were stratified according to the need for revascularization and then randomly assigned to treatment with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). Patients assigned to revascularization in the TAVR group underwent percutaneous coronary intervention, whereas those in the SAVR group had coronary artery bypass grafting. The primary end point was the rate of all-cause mortality or disabling stroke at 2 years. Results: Of 1660 subjects with attempted aortic valve implants, 332 (20%) were assigned to revascularization. They had a higher Society of Thoracic Surgeons risk score for mortality (4.8±1.7% versus 4.4±1.5%; P <0.01) and were more likely to be male (65.1% versus 54.2%; P <0.01) than the 1328 patients not assigned to revascularization. After randomization to treatment, there were 169 patients undergoing TAVR and percutaneous coronary intervention, 163 patients undergoing SAVR and coronary artery bypass grafting, 695 patients undergoing TAVR, and 633 patients undergoing SAVR. No significant difference in the rate of the primary end point was found between TAVR and percutaneous coronary intervention and SAVR and coronary artery bypass grafting (16.0%; 95% CI, 11.1–22.9 versus 14.0%; 95% CI, 9.2–21.1; P =0.62), or between TAVR and SAVR (11.9%; 95% CI, 9.5–14.7 versus 12.3%; 95% CI, 9.8–15.4; P =0.76). Conclusions: For patients at intermediate surgical risk with severe aortic stenosis and noncomplex coronary artery disease (SYNTAX score ≤22), a complete percutaneous approach of TAVR and percutaneous coronary intervention is a reasonable alternative to SAVR and coronary artery bypass grafting. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01586910. [ABSTRACT FROM AUTHOR]

In the Ethics subsection of the Methods, there is an error in the paragraph. Reference 1 Lukács Krogager M, Skals RK, Appel EVR, Schnurr TM, Engelbrechtsen L, Have CT, et al. (2018) Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography. [Extracted from the article]