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We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p <0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p <0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p <0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p <0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p <0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p >0.3 respectively. Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not. [ABSTRACT FROM AUTHOR]

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Background: Coronary artery disease (CAD) frequently coexists with severe aortic valve stenosis (AS) in patients planned for transcatheter aortic valve implantation (TAVI). How to manage CAD in this patient population is still an unresolved question. In particular, it is still not known whether fractional flow reserve (FFR) guided revascularization with percutaneous coronary intervention (PCI) is superior to medical treatment for CAD in terms of clinical outcomes.Study Design: The third Nordic Aortic Valve Intervention (NOTION-3) Trial is an open-label investigator-initiated, multicenter multinational trial planned to randomize 452 patients with severe AS and significant CAD to either FFR-guided PCI or medical treatment, in addition to TAVI. Patients are eligible for the study in the presence of at least 1 significant PCI-eligible coronary stenosis. A significant stenosis is defined as either FFR ≤0.80 and/or diameter stenosis >90%. The primary end point is a composite of first occurring all-cause mortality, myocardial infarction, or urgent revascularization (PCI or coronary artery bypass graft performed during unplanned hospital admission) until the last included patient have been followed for 1 year after the TAVI.Summary: NOTION-3 is a multicenter, multinational randomized trial aiming at comparing FFR-guided revascularization vs medical treatment of CAD in patients with severe AS planned for TAVI. [ABSTRACT FROM AUTHOR]

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

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: Complete revascularization in ST elevation myocardial infarction (STEMI) patients with multivessel disease has resulted in reduction in composite clinical endpoints in medium sized trials. Only one trial showed an effect on hard clinical endpoints, but the revascularization procedure was guided by angiographic evaluation of stenosis severity. Consequently, it is not clear how Fractional Flow Reserve (FFR)-guided percutaneous coronary intervention (PCI) affects hard clinical endpoints in STEMI.Methods and Results: The Ffr-gUidance for compLete non-cuLprit REVASCularization (FULL REVASC) - is a pragmatic, multicenter, international, registry-based randomized clinical trial designed to evaluate whether a strategy of FFR-guided complete revascularization of non-culprit lesions, reduces the combined primary endpoint of total mortality, non-fatal MI and unplanned revascularization. 1,545 patients were randomized to receive FFR-guided PCI during the index hospitalization or initial conservative management of non-culprit lesions. We found that in angiographically severe non-culprit lesions of 90-99% severity, 1 in 5 of these lesions were re-classified as non-flow limiting by FFR. Considering lesions of intermediate severity (70%-89%), half were re-classified as non-flow limiting by FFR. The study is event driven for an estimated follow-up of at least 2.75 years to detect a 9.9%/year>7.425%/year difference (HR = 0.74 at 80% power (α = .05)) for the combined primary endpoint.Conclusion: This large randomized clinical trial is designed and powered to evaluate the effect of complete revascularization with FFR-guided PCI during index hospitalization on total mortality, non-fatal MI and unplanned revascularization following primary PCI in STEMI patients with multivessel disease. Enrollment completed in September 2019 and follow-up is ongoing. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the safety of selective intracoronary hypothermia during primary percutaneous coronary intervention (PPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). Selective intracoronary hypothermia is a novel treatment designed to reduce myocardial reperfusion injury and is currently being investigated in the ongoing randomized controlled EURO-ICE (European Intracoronary Cooling Evaluation in Patients With ST-Elevation Myocardial Infarction) trial (NCT03447834). Data on the safety of such a procedure during PPCI are still limited. The first 50 patients with anterior STEMI treated with selective intracoronary hypothermia during PPCI were included in this analysis and compared for safety with the first 50 patients randomized to the control group undergoing standard PPCI. In-hospital mortality, occurrence of rhythm or conduction disturbances, stent thrombosis, onset of heart failure during the procedure, and subsequent hospital admission were assessed. In-hospital mortality was 0%. One patient in both groups developed cardiogenic shock. Atrial fibrillation occurred in 0 and 3 patients (P = 0.24), and ventricular fibrillation occurred in 5 and 3 patients (P = 0.72) in the intracoronary hypothermia group and control group, respectively. Stent thrombosis occurred in 2 patients in the intracoronary hypothermia group; 1 instance was intraprocedural, and the other occurred following interruption of dual-antiplatelet therapy consequent to an intracranial hemorrhage 6 days after enrollment. No stent thrombosis was observed in the control group (P = 0.50). Selective intracoronary hypothermia during PPCI in patients with anterior STEMI can be implemented within the routine of PPCI and seems to be safe. The final safety results will be reported at the end of the trial. [Display omitted] [ABSTRACT FROM AUTHOR]

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, P<.001) and risk of bleeding leading to hospitalization (adjusted HR 1.36, 95% CI 1.00-1.85, P=.050), and non-significant increased risk of ischemic stroke (adjusted HR 1.45, 95% CI 0.96-2.19, P=.08) and re-MI (adjusted HR 1.14, 95% CI 0.86-1.52, P=.35) with a median follow-up of 5.8 years. In NEW-AF patients, 38% received OAC therapy, which was associated with reduced long-term mortality (adjusted HR 0.69, 95% CI 0.47-1.00, P=.049).Conclusions: 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. [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]

Background: 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.Methods: 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.Results: ∑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).Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: 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).Methods: 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.Results: 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).Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Pathological Q-wave (QW) in the electrocardiogram (ECG) before primary percutaneous coronary intervention (primary PCI) is a strong prognostic marker in patients with ST-segment elevation myocardial infarction (STEMI). However, current binary QW criteria are either not clinically applicable or have a lack of diagnostic performance. Accordingly, we evaluated the association between duration, depth and area of QW and markers of the effect of reperfusion (reperfusion success).Methods: A total of 516 patients with their first STEMI had obtained an ECG before primary PCI and an acute cardiac magnetic resonance imaging (CMR) at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 92 (IQR, 89-96). The largest measurable QW in ECG was used for analysis of duration, depth and area of QW (QW morphology). The QW morphology was evaluated as a continuous variable in linear regression models and as a variable divided in four equally large groups.Results: The QW morphology as four equally large groups was significantly associated with all CMR endpoints (p ≤ 0.001) and showed a linear relationship (p ≤ 0.001) with final infarct size (for QW duration, β = 0.47; QW depth, β = 0.41 and QW area, β = 0.39), final infarct transmurality (for QW duration, β = 0.36; QW depth, β = 0.26 and QW area, β = 0.23) and final myocardial salvage index (for QW duration, β = -0.34; QW depth, β = -0.26 and QW area, β = -0.24).Conclusion: Although modest, the QW morphology in STEMI patients showed significant linear association with markers of reperfusion success. Hence, it is suggested that the term pathological is not used as a dichotomous parameter in patients with STEMI but rather evaluated on the basis of extent. [ABSTRACT FROM AUTHOR]

This study investigated the incidence and long-term prognostic importance of multiple myocardial scars in cardiac magnetic resonance (CMR) in a large contemporary cohort of patients with ST-segment elevation myocardial infarction (STEMI). Patients presenting with STEMI may have multiple infarctions/scars caused by multiple culprit lesions, previous myocardial infarction (MI) or procedure-related MI due to nonculprit interventions. However, the incidence, long-term prognosis, and distribution of causes of multiple myocardial scars remain unknown. CMR was performed in 704 patients with STEMI 1 day after primary percutaneous coronary intervention (PCI) and again 3 months later. Myocardial scars were assessed by late gadolinium enhancement (LGE). T2-weighted technique was used to differentiate acute from chronic infarctions. The presence of multiple scars was defined as scars located in different coronary territories. The combined endpoints of all-cause mortality and hospitalization for heart failure were assessed at 39 months (interquartile range [IQR]: 31 to 48 months). At 3 months, 59 patients (8.4%) had multiple scars. Of these, multiple culprits in STEMI were detected in 7 patients (1%), and development of a second nonculprit scar at follow-up occurred in 10 patients (1.4%). The most frequent cause of multiple scars was a chronic scar in the nonculprit myocardium. The presence of multiple scars was independently associated with an increased risk of all-cause mortality and hospitalization for heart failure (hazard ratio: 2.7; 95% confidence interval: 1.1 to 6.8; p = 0.037). Multiple scars were present in 8.4% of patients with STEMI and were independently associated with an increased risk of long-term morbidity and mortality. The presence of multiple myocardial scars on CMR may serve as a useful tool in risk stratification of patients following STEMI. (DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408) (Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization [PRIMULTI]; NCT01960933) [ABSTRACT FROM AUTHOR]

Objective: The DanGer Shock trial test the hypothesis that left ventricular (LV) mechanical circulatory support with Impella CP transvalvular microaxial flow pump improves survival in patients with ST segment elevation acute myocardial infarction complicated by cardiogenic shock (AMICS) compared to conventional guideline-driven treatment. This paper describes the rationale and design of the randomized trial, in addition to the baseline characteristics of the population screened and enrolled so far.Methods: The DanGer Shock study is a prospective, multicenter, open-label trial in patients with AMICS randomized 1:1 to Impella CP or current guideline-driven therapy with planned enrollment of 360 patients. Patients comatose after out of hospital cardiac arrest are excluded. Eligible patients are randomized immediately following shock diagnosis. Among patients randomized to receive Impella CP, the device is placed prior to angioplasty. The primary endpoint is all-cause mortality at 180 days. Baseline characteristics of patients screened and randomized in the DanGer Shock as of June 2018 are compared with 2 contemporary AMICS studies.Results: As of end of June 2018, 314 patients were screened and 100 patients were randomized. Patients had median arterial lactate of 5.5 mmol/L (interquartile range 3.7-8.8 mmol/L), median systolic blood pressure of 76 mmHg (interquartile range 70-88 mmHg), and median LV ejection fraction of 20% (interquartile range 10%-30%).Conclusion: The DanGer Shock trial will be the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. Baseline characteristics of the first 100 randomized patients indicate a population in profound cardiogenic shock. [ABSTRACT FROM AUTHOR]

Background: In patients with increased bleeding risk during dual antiplatelet therapy, the biolimus A9-coated BioFreedom, a stainless steel drug-coated stent devoid of polymer, has shown superiority compared to a bare-metal stent. The aim of this study was to investigate whether the polymer-free biolimus A9-coated BioFreedom is noninferior to a modern thin-strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention.Methods: The multicenter SORT OUT IX trial (NCT02623140) randomly assigned all-comers patients to treatment with the BioFreedom drug-coated stent or the biodegradable polymer Orsiro stent in 4 Danish University Hospitals. The primary end point target lesion failure is a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 12 months. Clinically driven event detection based on Danish registries will be used and continue through 5 years. Assuming an event rate of 4.2% in each stent group, 1,563 patients in each treatment arm will provide 90% power to detect noninferiority of the drug-coated BioFreedom stent with a noninferiority margin of 2.1%.Results: A total of 3,150 patients have been randomized and enrolled in the study.Conclusions: The SORT OUT IX trial will determine whether the drug-coated BioFreedom stent is noninferior to a modern biodegradable polymer Orsiro stent. [ABSTRACT FROM AUTHOR]

Abstract Objectives The authors sought to perform a randomized controlled trial to evaluate the clinical efficacy of combined examination with coronary computed tomography angiography (CTA) and computed tomography perfusion imaging (CTP) compared to coronary CTA alone. Background Stress myocardial CTP may increase diagnostic specificity when added to coronary CTA in patients suspected of having ischemic heart disease. Methods Patients recently hospitalized for acute-onset chest pain, who had acute coronary syndrome had been ruled out by normal electrocardiograms, normal troponin levels, and relief of symptoms, and who had a clinical indication for outpatient noninvasive testing, were screened for inclusion in the CATCH-2 (CArdiac cT in the treatment of acute CHest pain 2) trial (NCT02014311). Patients were randomized 1:1 to examination with coronary CTA or coronary CTA+CTP. The primary endpoint was the frequency of coronary revascularization among patients referred for invasive coronary angiography (ICA) based on index computed tomography evaluation. Secondary endpoints were invasive procedural complications at index-related ICA, post-index cardiac death, hospital admittance because of recurrence of chest pain, unstable angina pectoris, or acute myocardial infarction, ICA, and revascularization. Results Among 300 patients allocated to the coronary CTA+CTP group, 41 (14%) were referred for ICA compared with 89 (30%) allocated to coronary CTA (p < 0.0001). The primary endpoint occurred in 50% of coronary CTA+CTP patients versus 48% of invasively examined patients (p = 0.85). The total number of revascularizations was significantly lower in the coronary CTA+CTP group compared to the coronary CTA group (n = 20 [7%] vs. n = 42 [14%]; p = 0.0045). At median follow-up of 1.5 years, the occurrence of secondary endpoints was similar in the 2 groups. Conclusions A post-discharge diagnostic strategy of coronary CTA+CTP safely reduces the need for invasive examination and treatment in patients suspected of having ischemic heart disease. (CArdiac cT in the treatment of acute CHest pain 2–Myocardial CT Perfusion [CATCH2]; NCT02014311) Graphical abstract [ABSTRACT FROM AUTHOR]

Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI.Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality.Results: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P < .001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P < .001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all < .001).Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population. [ABSTRACT FROM AUTHOR]

Background: Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI.Methods/design: The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new AMI, or stent thrombosis at 1 year.Implications: The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI. [ABSTRACT FROM AUTHOR]

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]

Aims: Familial hypercholesterolemia (FH) is a common genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease. The aim of this study was to examine the prevalence and prognostic significance of possible FH in patients with myocardial infarction (MI).Methods and Results: By individual-level linkage of data from the Eastern Danish Heart Registry and national administrative registries, a study population of patients referred for coronary angiography due to MI was selected. The study population was divided into "unlikely FH" and "possible FH" based on the Dutch Lipid Clinic Network criteria, which included a plasma low-density lipoprotein cholesterol (LDL-C) and age for onset of cardiac disease. A score of ≥3 points was used as the cutpoint between the 2 groups. Among the study population of 13,174 MI patients, 1,281 (9.7%) had possible FH. These patients were younger (59.1 vs 65.7 years, P ≤ .0001), had similar levels of comorbidities, and were treated more aggressively with cholesterol-lowering drugs compared with patients with unlikely FH. During a median of 3.3 years of follow-up, the unadjusted and adjusted event rates of recurrent MI were higher in patients with possible FH compared with unlikely FH (16% vs 11%, adjusted hazard ratio 1.28, 95% CI 1.09-1.51, P = .003.). Differences in adjusted all-cause mortality were not statistically significant (17% vs 23%, adjusted hazard ratio 0.89 [0.74-1.04], P = .1).Conclusion: We found that MI patients with possible FH have higher risk of recurrent MI but similar risk of mortality compared with unlikely FH patients. Further studies on secondary prevention are warranted. [ABSTRACT FROM AUTHOR]

Aims: Patients admitted with chest pain are a diagnostic challenge because the majority does not have coronary artery disease (CAD). Assessment of CAD with coronary computed tomography angiography (CCTA) is safe, cost-effective, and accurate, albeit with a modest specificity. Stress myocardial computed tomography perfusion (CTP) has been shown to increase the specificity when added to CCTA, without lowering the sensitivity. This article describes the design of a randomized controlled trial, CATCH-2, comparing a clinical diagnostic management strategy of CCTA alone against CCTA in combination with CTP.Methods: Patients with acute-onset chest pain older than 50 years and with at least one cardiovascular risk factor for CAD are being prospectively enrolled to this study from 6 different clinical sites since October 2013. A total of 600 patients will be included. Patients are randomized 1:1 to clinical management based on CCTA or on CCTA in combination with CTP, determining the need for further testing with invasive coronary angiography including measurement of the fractional flow reserve in vessels with coronary artery lesions. Patients are scanned with a 320-row multidetector computed tomography scanner. Decisions to revascularize the patients are taken by the invasive cardiologist independently of the study allocation. The primary end point is the frequency of revascularization. Secondary end points of clinical outcome are also recorded.Discussion: The CATCH-2 will determine whether CCTA in combination with CTP is diagnostically superior to CCTA alone in the management of patients with acute-onset chest pain. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention. Background Prasugrel is one of the preferred P2Y 12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients. Methods Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days. Results Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36). Conclusions This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416 ; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701 ). [ABSTRACT FROM AUTHOR]

Background In patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction, ischemic postconditioning has been shown to reduce infarct size, but the effect on clinical outcome has not been tested in a large randomized trial. In addition, deferring stent implantation in the infarct-related lesion 1 to 3 days after acute opening of the infarct-related artery could have protective effects, by reducing the risk of injury caused by distal embolization and microvascular obstruction. Finally, a considerable fraction of patients present with lesions in other coronary artery branches than the infarct-related artery. Whether a strategy of complete or partial revascularization of these patients should be preferred remains uncertain. Study design The DANAMI 3 trial program was designed to investigate 3 different randomized treatment strategies in patients with ST-segment elevation myocardial infarction: (1) ischemic postconditioning versus conventional treatment with a primary end point of death and hospitalization for heart failure; (2) deferring stent implantation in the infarct-related lesion versus conventional treatment with a primary end point of death, hospitalization for heart failure, reinfarction, and repeat revascularization; and (3) treatment of the culprit lesion only versus fractional flow reserve–guided complete revascularization in patients with multivessel disease, with a primary end point of death, reinfarction, and repeat revascularization. Summary The DANAMI 3 trial program will determine whether either of 2 approaches to reduce reperfusion injury and distal microvascular obstruction with postconditioning or deferred stent implantation will translate into improved clinical outcome and whether patients with multivessel disease undergoing primary percutaneous coronary intervention will benefit from a strategy of complete or partial revascularization. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: The reduction of left ventricular ejection fraction (LVEF) following ST-segment elevation myocardial infarction (STEMI) is a result of infarcted myocardium and may involve dysfunctional but viable myocardium. An index that may quantitatively determine whether LVEF is reduced beyond the expected value when considering only infarct size (IS) has previously been presented based on cardiac magnetic resonance (CMR). The purpose of this study was to introduce the index based on the electrocardiogram (ECG) and compare indices based on ECG and CMR. Method and Results: In 55 patients ECG and CMR were obtained 3months after STEMI treated with primary percutaneous coronary intervention. Significant, however moderate inverse relationships were found between measured LVEF and IS. Based on IS and LVEF an IS estimated LVEF was derived and an MI–LVEF mismatch index was calculated as the difference between measured LVEF and IS estimated LVEF. In 41 (74.5%) of the patients there was agreement between the ECG and CMR indices in regards to categorizing indices as >10 or≤10 and generally no significant difference was detected, mean difference of 1.26 percentage points (p=0.53). Conclusion: The study found an overall good agreement between MI–LVEF mismatch indices based on ECG and CMR. The MI–LVEF mismatch index may serve as a tool to identify patients with potentially reversible dysfunctional but viable myocardium, but future studies including both ECG and CMR are needed. [Copyright &y& Elsevier]

Objectives: This study sought to compare the long-term effects of drug-eluting stent (DES) compared with bare-metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Background: The randomized DEDICATION (Drug Elution and Distal Protection in Acute Myocardial Infarction) trial evaluated the outcome after DES compared with BMS implantation in patients with STEMI undergoing primary percutaneous coronary intervention. Methods: Patients with a high-grade stenosis/occlusion of a native coronary artery presenting with symptoms <12 h and ST-segment elevation were enrolled after giving informed consent. Patients were randomly assigned to receive a DES or a BMS in the infarct-related lesion. Patients were followed for at least 5 years, and clinical endpoints were evaluated from population registries and hospital charts. The main endpoint was the occurrence of the first major adverse cardiac event (MACE), defined as cardiac death, nonfatal recurrent myocardial infarction, and target lesion revascularization. Results: Complete clinical status was available in 623 patients (99.5%) at 5 years follow-up. The combined MACE rate was insignificantly lower in the DES group (16.9% vs. 23%), mainly driven by a lower need of repeat revascularization (p = 0.07). Whereas the number of deaths from all causes tended to be higher in the DES group (16.3% vs. 12.1%, p = 0.17), cardiac mortality was significantly higher (7.7% vs. 3.2%, p = 0.02). The 5-year stent thrombosis rates were generally low and similar between the DES and the BMS groups. No cardiac deaths occurring within 1 month could be clearly ascribed to stent thrombosis, whereas stent thrombosis was involved in 78% of later-occurring deaths. Conclusions: The 5-year MACE rate was insignificantly different, but the cardiac mortality was higher after DES versus BMS implantation in patients with STEMI. Stent thrombosis was the main cause of late cardiac deaths. [Copyright &y& Elsevier]

Abstract: Background and Purpose: One third of patients treated with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction develop a secondary increase in electrocardiographic ST segment (ST peak) during reperfusion. The purpose was to determine the clinical importance of ST peak during primary PCI. Methods: A total of 363 patients with ST-elevation myocardial infarction were stratified to no ST peak or ST peak. Final infarct size and ejection fraction (EF) were assessed by cardiovascular magnetic resonance. Results: Patients with ST peak had a larger infarct size (14% vs 10%; P = .003) and lower EF (53% vs 57%; P = .022). Rates of cardiac mortality (8% vs 3%; P = .047) and cardiac events (cardiac mortality and admission for heart failure; 19% vs 10%; P = .018) were higher among patients with ST peak, but not all-cause mortality (8% vs 5%; P = .46). In a multivariable Cox regression analysis, ST peak remained significantly associated with cardiac events (adjusted hazard ratio, 2.03 [1.08-3.82]). Conclusion: ST peak during primary PCI is related to larger final infarct size, a reduced EF, and adverse cardiac clinical outcome. [Copyright &y& Elsevier]

Background: The association between reperfusion delay and myocardial damage has previously been assessed by evaluation of the duration from symptom onset to invasive treatment, but results have been conflicting. System delay defined as the duration from first medical contact to first balloon dilatation is less prone to bias and is also modifiable. The purpose was to evaluate the impact of system delay on myocardial salvage index (MSI) and infarct size in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention (PCI). Methods: In patients with ST-elevation myocardial infarction, MSI and final infarct size were assessed using cardiovascular magnetic resonance. Myocardial area at risk was measured within 1 to 7 days, and final infarct size was measured 90 ± 21 days after intervention. Patients were grouped according to system delay (0 to 120, 121 to 180, and >180 minutes). Results: In 219 patients, shorter system delay was associated with a smaller infarct size (8% [interquartile range 4-12%], 10% [6-16%], and 13% [8-17%]; P < .001) and larger MSI (0.77 [interquartile range 0.66-0.86], 0.72 [0.59-0.80], and 0.68 [0.64-0.72]; P = .005) for a system delay of up to 120, 121 to 180, and >180 minutes, respectively. A short system delay as a continuous variable independently predicted a smaller infarct size (r = 0.30, P < .001) and larger MSI (r = −0.25, P < .001) in multivariable linear regression analyses. Finally, shorter system delay (0-120 minutes) was associated with improved function (P = .019) and volumes of left ventricle (P = .022). Conclusions: A shorter system delay resulted in smaller infarct size, larger MSI, and improved LV function in patients treated with primary PCI. Thus, this study confirms that minimizing system delay is crucial for primary PCI-related benefits. [ABSTRACT FROM AUTHOR]

Background: Left ventricular (LV), right ventricular (RV), and left atrial (LA) volumes and functions contain important prognostic information in ischemic heart disease. Because multidetector computed tomography (MDCT) has high spatial resolution, this method may be optimal to obtain this information. Objective: We evaluated automated assessment for MDCT, by comparing it with cardiac magnetic resonance (CMR). Methods: Fifty-three patients with previous myocardial infarction were scanned with 1.5 Tesla CMR and 64-slice MDCT. End-diastolic volume, end-systolic volume, stroke volume, and ejection fraction (EF) were assessed for the left and right ventricle with automatic MDCT software and manual CMR software. LV myocardial mass and cyclic changes in LA volume were derived. Results: The mean age of patients was 61 ± 10 years, 40 (75%) were men. Automated MDCT segmentation was possible in all but 2 patients. The average duration of image processing was 21 ± 4 minutes by CMR and 11 ± 4 minutes by MDCT. Bland-Altman plots showed good agreement between MDCT and CMR with only small bias. LVEF by CMR was 56% ± 10% and by MDCT 61% ± 11%, mean difference of −5% (limits of agreement, −18% to 8%), and P < 0.001. RVEF by CMR was 60% ± 5% and by MDCT 56% ± 8%, mean difference of 5% (limits of agreement, −10% to 20%), and P < 0.001. LA fractional change by CMR was 49% ± 9% and by MDCT 45% ± 9%, mean difference of 4% (limits of agreement, −12% to 20%), and P ≤ 0.001. Conclusion: LV, RV, and LA volumes and functions may be evaluated fast and reliably with the use of automated assessment and cardiac MDCT, with good agreement to CMR. Accurate assessment of cardiac chambers with MDCT appears possible in clinical practice. [Copyright &y& Elsevier]

Abstract: Background and Purpose: Recent studies have shown that the Selvester QRS score is significantly correlated with delayed enhancement-magnetic resonance imaging (DE-MRI) measured myocardial infarct (MI) size in reperfused ST elevation MI (STEMI). This study further tests the hypothesis that Selvester QRS score correlates well with MI size determined by DE-MRI in reperfused STEMI. Methods and Results: The relationship was evaluated retrospectively in 55 first-time STEMI patients 3 months after receiving primary percutaneous coronary intervention. Selvester QRS score and DE-MRI MI size were significantly correlated, r = 0.41 (P < .01). The difference between the Selvester QRS score and DE-MRI was 5.8% MI of the left ventricle (95% confidence interval, 2.9%-8.6%). Furthermore, increasing difference between Selvester QRS score and DE-MRI was observed with increasing MI size. Conclusion: Selvester QRS score correlated only moderately with DE-MRI MI size. Selvester QRS score overestimated MI size. [Copyright &y& Elsevier]

Background: Ischemic postconditioning (IPost) during primary percutaneous coronary intervention (PPCI) is suggested to reduce myocardial damage. However, the association with ST-segment resolution (STR) and clinical outcome is not determined. The primary aim of this study was to evaluate the association of IPost with STR and clinical outcome. Secondly, we sought to determine the relationship between STR and cardiac magnetic resonance (CMR) parameters in these patients. Methods: One hundred eighteen patients referred for PPCI were randomly assigned to either conventional PPCI or PPCI with IPost. In a single electrocardiographic lead, STR was determined. Treatment modalities were compared as regards STR, ST-segment elevation, and the number of patients achieving complete-STR (≥70%), incomplete-STR (30%-70%), and no-STR (<30%). Patients were evaluated for clinical outcome after 15 months. Furthermore, patients with and without complete-STR were compared as regards CMR parameters. Results: There was a tendency toward a better outcome with IPost for the number of patients achieving complete-STR (55% vs 63%; P = .09), ST-segment elevation (1.41 vs 1.12 mm; P = .07), and New York Heart Association class (P = .06). No difference in other cardiac events was observed. Furthermore, data determine that patients with complete-STR have smaller infarct size (12.9% vs 21.1%; P < .01) and a better ejection fraction (55.7% vs 47.7%; P < .01). Conclusions: Patients treated with IPost are suggested to have improved STR and New York Heart Association classification. Infarct size and the functional CMR parameters were better in the patients with complete-STR; as to this, single-lead STR remains an important predictor for successful treatment in patients treated with IPost. [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]

Background: Coronary restenosis is more common in a total coronary occlusion (TCO) than other lesion types after implantation of bare metal stents (BMS). But whereas sirolimus-eluting stents (SES) have been shown to improve the outcomes in simple coronary artery lesions, data on their efficacy in complex coronary lesions are scarce. Methods: We enrolled 127 patients with coronary artery disease and a TCO ≥ 15 mm in length to have either SES or BMS implanted after successful recanalization. Outcome measures included the minimal lumen diameter, the late lumen loss, and angiographic restenosis (>50% diameter stenosis) at 6 months follow-up and the occurrence of target vessel failure during a 7-month period. Results: The patients were well matched in demographic and angiographic baseline characteristics, and 20% had diabetes. The reference vessel was 2.92 mm in mean, and the lesion length was 25.2 mm. At follow-up, patients who received SES had a minimal lumen diameter of 2.49 mm compared with 1.46 mm in those who received BMS (P = .015), 0% versus 38% developed restenosis (P < .001), lumen loss was −0.05 versus 0.99 mm (P < .001), and the target vessel failure rate 5% with SES versus 35% with BMS (P < .001). Stent thrombosis occurred in 1 patient in the BMS group. Conclusions: Implantation of SES is safe, and it markedly reduces angiographic restenosis and the occurrence of adverse events in patients with a TCO. [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]

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]

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 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]

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]

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]