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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.

BACKGROUND: Cohort studies have revealed an increased risk for ventricular fibrillation (VF) and sudden cardiac death (SCD) in patients with atrial fibrillation (AF). In this study, we hypothesized that single nucleotide polymorphisms (SNP) previously associated with AF may be associated with the risk of VF caused by first ST-segment elevation myocardial infarction (STEMI).METHODS: We investigated association of 24 AF-associated SNPs with VF in the prospectively assembled case-control study among first STEMI-patients of Danish ancestry.RESULTS: We included 257 cases (STEMI with VF) and 537 controls (STEMI without VF). The median age at index infarction was 60 years for the cases and 61 years for the controls (p = 0.100). Compared to the control group, the case group was more likely to be male (86% vs. 75%, p = 0.001), have a history of AF (7% vs. 2%, p = 0.006) or hypercholesterolemia (39% vs. 31%, p = 0.023), and a family history of sudden death (40% vs. 25%, p CONCLUSION: In this study, we found that the 24 AF-associated SNPs may not be involved in increasing the risk of VF. Larger VF cohorts and use of new next generation sequencing and epigenetic may in future identify additional AF and VF risk loci and improve our understanding of genetic pathways behind the two arrhythmias.

Cardiac magnetic resonance (CMR) imaging is becoming a routine diagnostic and therapy planning tool for some cardiovascular diseases. It is still challenging to properly analyse the acquired data, and the currently available measures do not exploit the rich characteristics of that data. Advanced analysis and modelling techniques are increasingly used to extract additional information from the images, in order to define metrics describing disease manifestations and to quantitatively compare patients. Many techniques share a common bottleneck caused by the image processing required to segment the images and convert the segmentation to a usable computational domain for analysis/modelling. To address this, we present a comprehensive pipeline to go from CMR images to computational bi-ventricle meshes. The latter can be used for biophysical simulations or statistical shape analysis. The provided tutorial describes each step and the proposed pipeline, which makes use of tools that are available open-source. The pipeline was applied to a data-set of myocardial infarction patients, from late gadolinium enhanced CMR images, to analyse and compare structure in these patients. Examples of applications present the use of the output of the pipeline for patient-specific biophysical simulations and population-based statistical shape analysis.

Myocardial infarction results in changes in the structure and tissue deformation of the ventricles. In some cases, the development of the disease may trigger an arrhythmic event, which is a major cause of death within the first twenty four hours after the infarction. Advanced analysis methods are increasingly used in order to discover particular characteristics of the myocardial infarction development that lead to the occurrence of arrhythmias. However, such methods usually consider only a single feature or combine separate analyses from multiple features in the analytical process. In an attempt to address this, we propose to use cardiac magnetic resonance imaging to extract data on the shape of the ventricles and volume and location of the infarct zone, and to combine them within one analytical model through a multiple kernel learning framework. The proposed method was applied to a cohort of 46 myocardial infarction patients. The location, rather than the volume, of the infarct region was found to be correlated with arrhythmic events and the proposed combination of kernels yielded excellent accuracy (100%) in distinguishing between patients that did and did not present at the hospital with ventricular fibrillation.

AIMS Selective use of DES only in patients at higher risk of MACE is common practice, particularly in health care systems with a large premium payable for DES. We aimed to identify subgroups of patients in which the use of BMS in primary percutaneous coronary intervention (PPCI) for STEMI can still be justified. METHODS AND RESULTS We performed a patient-level pooled analysis of COMFORTABLE-AMI and EXAMINATION comparing contemporary DES with BMS in PPCI. A risk score was applied using three parameters: lesion length>15mm, vessel size

Changes in left ventricular (LV) function using echocardiography and cardiac magnetic resonance (CMR) imaging were assessed in a contemporary ST-segment elevation myocardial infarction (STEMI) population to assess whether repeated imaging is necessary.In a prospective study patients with first STEMI were treated with primary percutaneous coronary intervention (PCI) and examined with 2D-echocardiography and CMR at baseline (72 h) and at a three-month follow-up.A total of 138 patients were included (60±11 years). Using 2D-echocardiography at baseline preserved left ventricular ejection fraction (LVEF) (50%) was found in 48 patients (35%), mild/moderate systolic dysfunction (35-50%) in 76 patients (55%) and severe dysfunction (35%) in 14 patients (10%). Improvement in systolic function group was seen in 58 patients (64%) and 11 patients (79%) with severe systolic dysfunction at baseline were re-classified as having preserved or mild/moderate systolic dysfunction at follow-up. Irrespective of baseline LVEF, deterioration in systolic function group was noted in 14 patients (11%), but no patients declined from preserved to severe systolic dysfunction. The recovered myocardium measured with the myocardial salvage index by CMR was significantly lower with declining LVEF at baseline.The majority of patients with severely depressed LVEF immediately after STEMI significantly improved systolic function after three months. This study emphasises the importance of a repeated LV function assessment at follow-up in patients with mild/moderate or severe systolic dysfunction after STEMI, but re-assessment may not be needed in patients with preserved LVEF at baseline.

To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI). There is a wide variability in the platelet reactivity to clopidogrel and HTPR has been associated with a poor prognosis.In this observational study, 923 consecutive patients without ST-elevation myocardial infarction (STEMI) and adequately pre-treated with clopidogrel were screened for HTPR with multiple electrode aggregometry after assessment of the coronary anatomy. Patients were grouped based on their response to clopidogrel and the assigned antiplatelet strategy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or stent thrombosis.HTPR was demonstrated in 237 patients (25.7%). Of these, 114 continued on conventional clopidogrel therapy, while the remaining 123 received intensified antiplatelet therapy with either double-dose clopidogrel (150 mg daily, n = 55) or the newer P2Y12-inhibitors, prasugrel or ticagrelor (n = 68) for at least 30 days after the index procedure. The median follow-up was 571 days (interquartile range, 373-746). Intensifying antiplatelet therapy reduced the rate of the composite endpoint (p0.001). After adjustment for potential confounders, HTPR in combination with conventional clopidogrel therapy remained independently associated with an increased risk of cardiovascular events (hazard ratio (HR), 2.92; 95% CI, 1.90-4.48), whereas intensified treatment reduced the risk to a level equivalent to that of patients exhibiting normal platelet reactivity (HR, 1.08; 95% CI, 0.59-1.99).Tailored antiplatelet therapy significantly reduced the event rate in patients exhibiting HTPR prior to PCI.

OBJECTIVES: The impact of angiographically visible distal embolization (DE) and distal protection occurring during primary percutaneous coronary intervention (PCI) on long-term outcome has not been studied in a contemporary ST-segment elevation myocardial infarction (STEMI) cohort. To evaluate the association between DE and long-term outcome in STEMI patients treated with primary PCI with or without distal protection.METHODS AND RESULTS: In this post-hoc analysis of a randomized study, 591 STEMI patients were randomized to conventional primary PCI or primary PCI with distal protection and followed for 5 years. There was no statistically significant difference in MACE rate between patients treated with or wthout distal protection (19% versus 25%; p=0.10). There seemed to be interaction between distal protection and DE in major adverse cardiac events (MACE) (p=0.08), mortality (p=0.02) and reinfarction (p=0.06), but not admission for heart failure (p=0.40). DE was related to increased risk of admission for heart failure independently of distal protection (12.0% versus 5.0; p=0.015). The MACE rate for patients treated with standard PCI with DE was 31.3% compared to 24.8% for patients without DE (p=0.30), and 44.4% for patients treated with distal protection with DE compared to 17.9% for patients without DE (p=0.005). DE was not related to mortality (p=0.52) or reinfarction (p=0.52) among patients treated with standard PCI, but was related to higher rates of mortality (p=0.012) and reinfarction (p=0.008) when distal protection was used.CONCLUSION: DE occurred in 11% of STEMI patients treated with conventional primary PCI, and was associated with increased risk of development of heart failure. Distal protection did not improve the 5-years MACE rate, and might even aggravate the prognosis following DE, but this should only be considered hypothesis-generating.

The objective was to investigate the potential protective effects of two conditioning methods, on myocardial ischemic and reperfusion injury in relation to cardiac surgery.Totally 68 patients were randomly assigned to either a control group (n = 23), a remote ischemic preconditioning (RIPC) group (n = 23) or a glucagon-like peptide-1 (GLP-1) analogue group (n = 22). The RIPC protocol consisted of three cycles of upper limb ischemia. The GLP-1 analogue protocol consisted of intravenous infusion with exenatide. The primary endpoint was postoperative cardiac enzyme release. The other secondary endpoints were metabolic parameters related to myocardial ischemia, measured using microdialysis technique, as well as other operative- and postoperative data.Postoperative cardiac enzyme release indicated a possible beneficial effect of the interventions, but the difference did not reach statistical significance. RIPC showed a trend toward lower levels (p = 0.07). We managed to establish a functional myocardial microdialysis model, but we were unable to demonstrate clear protective effects.We were in this prospective randomized proof-of-concept trial, unable to show distinct protective effects of the studied conditioning methods. However, this trial can hopefully contribute to generate a productive discussion concerning limitations and future use of cardiac conditioning as well as microdialysis technique.

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 3 months 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.

Background: In-hospital mortality in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA) is ≈50%. In OHCA patients, the leading cause of death is neurological injury secondary to ischemia and reperfusion. Glucagon-like peptide-1 analogs are approved for type 2 diabetes mellitus; preclinical and clinical data have suggested their organ-protective effects in patients with ischemia and reperfusion injury. The aim of this trial was to investigate the neuroprotective effects of the glucagon-like peptide-1 analog exenatide in resuscitated OHCA patients. Methods: We randomly assigned 120 consecutive comatose patients resuscitated from OHCA in a double-blind, 2-center trial. They were administered 17.4 μg exenatide (Byetta) or placebo over a 6-hour and 15-minute infusion, in addition to standardized intensive care including targeted temperature management. The coprimary end points were feasibility, defined as initiation of the study drug in >90% patients within 240 minutes of return of spontaneous circulation, and efficacy, defined as the geometric area under the neuron-specific enolase curve from 24 to 72 hours after admission. The main secondary end points included a composite end point of death and poor neurological function, defined as a Cerebral Performance Category score of 3 to 5 assessed at 30 and 180 days. Results: The study drug was initiated within 240 minutes of return of spontaneous circulation in 96% patients. The median blood glucose 8 hours after admission in patients receiving exenatide was lower than that in patients receiving placebo (5.8 [5.2–6.7] mmol/L versus 7.3 [6.2–8.7] mmol/L, P Conclusions: Acute administration of exenatide to comatose patients in the intensive care unit after OHCA is feasible and safe. Exenatide did not reduce neuron-specific enolase levels and did not significantly improve a composite end point of death and poor neurological function after 180 days. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02442791.

Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD.

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research. DJH was funded by the British Heart Foundation (Grant Number FS/10/039/28270), the Rosetrees Trust, and is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. HEB was funded by the Danish Council for Independent Research (11-108354), the Danish Council for Strategic Research (11-115818), the Novo-Nordisk Foundation and Trygfonden. PF was funded by the Hungarian Scientific Research Fund (OTKA K 109737 and ANN 107803). HACF is funded by a Startup Grant of the ``Excellence Cluster Cardio-Pulmonary System'' (ECCPS) from the German Research Foundation (DFG, Bonn, Germany) and the ``Peter und Traudl Engelhorn-Stiftung'' (Weilheim, Germany) and in part by the Russian Government Program for competitive growth of Kazan Federal University, Kazan (Russian Federation). GH was supported by the German Research Foundation (He 1320/18-3 and SFB 1116/B8). TM was funded by the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research \#23591086, \#2646113). MRS was funded by Novo-Nordisk Foundation. DG-D is supported by the Spanish Institute of Health, Instituto de Salud Carlos III (Grants PIE 13/00027, RETICS-RIC, RD12/0042/0021, and PI14/01431). RS and PF were funded by the European Foundation for the Study of Diabetes (EFSD) New Horizons Collaborative Research Initiative from the European Association for the Study of Diabetes (EASD) and by the European Cooperation in Science and Technology (COST EU-ROS). PF was funded by the Hungarian Scientific Research Fund (OTKA K 109737 and ANN 107803). Sí

High on-treatment platelet reactivity (HTPR) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). The antiplatelet effect and safety of prasugrel was compared to that of double-dose clopidogrel in patients with stable coronary artery disease or acute coronary syndrome (ACS) exhibiting HTPR on clopidogrel and treated with PCI, using multiple electrode aggregometry (MEA) to assess platelet reactivity. Of 923 patients screened, 237 (25.7%) exhibited HTPR. Of these, 106 were eligible for participation in a randomized trial comparing two intensified antiplatelet regimen: 52 were assigned to double maintenance-dose clopidogrel and 54 to standard-dose prasugrel. At 1 month, tailoring antiplatelet therapy improved platelet inhibition to a level considered as therapeutic in 73.1% of patients. Prasugrel entailed greater platelet inhibition (p = 0.02) and a lower rate of persisting HTPR at follow-up compared to double-dose clopidogrel (HTPR persisted in 20.4% and 42% respectively, p = 0.02). Within the 30-day follow-up, no major bleeds were observed and the incidence of major adverse cardiovascular events (MACE) was similar in the two treatment arms. Prasugrel demonstrated superiority to double-dose clopidogrel in overcoming HTPR and reducing platelet activity. Intensifying antiplatelet therapy in both ACS and stable angina pectoris (SAP) patients exhibiting HTPR prior to PCI was well tolerated.

Positive-pressure ventilation (PPV) is widely used for treatment of acute cardiorespiratory failure, occasionally at the expense of compromised cardiac function and arterial blood pressure. The explanation why has largely rested on interpretation of intracardiac pressure changes. We evaluated the effect of PPV on the central circulation by studying cardiac chamber volumes with cardiac magnetic resonance imaging (CMR). We hypothesized that PPV lowers cardiac output (CO) mainly via the Frank-Starling relationship. In 18 healthy volunteers, cardiac chamber volumes and flow in aorta and the pulmonary artery were measured by CMR during PPV levels of 0, 10, and 20 cmH2O applied via a respirator and a face mask. All cardiac chamber volumes decreased in proportion to the level of PPV. Following 20-cmH2O PPV, the total diastolic and systolic cardiac volumes (±SE) decreased from 605 (±29) ml to 446 (±29) ml ( P < 0.001) and from 265 (±17) ml to 212 (±16) ml ( P < 0.001). Left ventricular stroke volume decreased by 27 (±4) ml/beat; heart rate increased by 7 (±2) beats/min; and CO decreased by 1.0 (±0.4) l/min ( P < 0.001). From 0 to 20 cmH2O, right and left ventricular peak filling rates decreased by −146 (±32) and −187 (±64) ml/s ( P < 0.05) but maximal emptying rates were unchanged. Cardiac filling and output decrease with increasing PPV in healthy volunteers. The decrease is seen even at low levels of PPV and should be taken into account when submitting patients to mechanical ventilation with positive pressures. The decrease in CO is fully explained by the Frank-Starling mechanism.

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 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.

Aims: Disturbance in the flow of an infarct-related artery due to embolisation of thrombus and plaque material occurs frequently during primary percutaneous coronary intervention (PCI) and is associated with impaired prognosis. The aim of the present study was to minimise the risk of embolisation during PCI in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results: Of 124 consecutive patients with STEMI, thrombectomy and/or balloon dilatation was performed in 110 (89%). Stent implantation was deferred in 113 (91%) patients who then comprised the study group. In 38% of the patients stent implantation was deemed unnecessary at the second examination because of

Aims Tailored heart failure treatment and risk assessment in patients following ST-segment elevation myocardial infarction (STEMI) is mainly based on the assessment of the left ventricular (LV) ejection fraction (EF). Assessment of the final infarct size in addition to the LVEF may improve the prognostic evaluation. To evaluate the prognostic importance of the final infarct size measured by cardiovascular magnetic resonance (CMR) in patients with STEMI. Methods and results In an observational study the final infarct size was measured by late gadolinium enhancement CMR 3 months after initial admission in 309 patients with STEMI. The clinical endpoint was a composite of all-cause mortality and admission for heart failure. During the follow-up period of median 807 days (IQR: 669–1117) 35 events (5 non-cardiac deaths, 3 cardiac deaths, and 27 admissions for heart failure) were recorded. Patients with a final infarct size ≥median had significantly higher event rates than patients with a final infarct size

Background— Pathological early Q waves (QW) are associated with adverse outcomes in patients with ST-segment–elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) may therefore be less beneficial in patients with QW than in patients without QW. Myocardial salvage index and microvascular obstruction (MVO) are markers for reperfusion success. Thus, to clarify the benefit from primary PCI in STEMI patients with QW, we examined the association between baseline QW and myocardial salvage index and MVO in STEMI patients treated with primary PCI. Methods and Results— The ECG was assessed before primary PCI for the presence of QW (early) in 515 STEMI patients. The patients underwent a cardiac magnetic resonance imaging scan at day 1 (interquartile range [IQR], 1–1) and again at day 92 (IQR, 89–96). Early QW was observed in 108 (21%) patients and was related to smaller final myocardial salvage index (0.59 [IQR, 0.39–0.69] versus 0.65 [IQR, 0.46–0.84]; P P P =0.03) and MVO (β=0.18; P =0.001) after adjusting for potential confounders. Conclusions— Patients presenting with their first STEMI and early QW in the ECG had smaller myocardial salvage index and more extensive MVO than non-QW despite treatment within 12 hours after symptom onset. However, final myocardial salvage index in patients with QW was substantial, and patients with QW still benefit from primary PCI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01435408.

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.

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 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.

AIMS: We aimed to assess the effect of exenatide treatment as an adjunct to primary percutaneous coronary intervention (PCI) on long-term clinical outcome.METHODS AND RESULTS: We performed a post hoc analysis in 334 patients with a first STEMI included in a previous study randomised to exenatide (n=175) or placebo (n=159) as an adjunct to primary PCI. The primary endpoint was a composite of all-cause mortality and admission for heart failure during a median follow-up of 5.2 years (interquartile range: 5.0-5.5). Secondary endpoints were all-cause mortality and admission for heart failure, individually. The primary composite endpoint occurred in 24% in the exenatide group versus 27% in the placebo group, p=0.44 (HR 0.80, p=0.35). Admission for heart failure was lower in the exenatide (11%) compared to the placebo group (20%) (HR 0.53, p=0.042). All-cause mortality occurred in 14% in the exenatide group versus 9% in the placebo group (HR 1.45, p=0.20).CONCLUSIONS: In this post hoc analysis of patients with a STEMI, treatment with exenatide at the time of primary PCI did not reduce the primary composite endpoint or the secondary endpoint of all-cause -mortality. However, exenatide treatment reduced the incidence of admission for heart failure.

Background Attenuating the neurological damage occurring after out-of-hospital cardiac arrest is an ongoing research effort. This dual-centre study investigates the neuroprotective effects of the glucagon-like-peptide-1 analogue Exenatide administered within 4 hours from the return of spontaneous circulation to comatose patients resuscitated from out-of-hospital cardiac arrest. Methods/design This pilot study will randomize a total of 120 unconscious patients with sustained return of spontaneous circulation after out-of-hospital cardiac arrest undergoing targeted temperature management in a blinded one-to-one fashion to a 6-hour and 15-minute infusion of either Exenatide or placebo. Patients are eligible for inclusion if resuscitated from cardiac arrest with randomization from 20 minutes to 240 minutes after return of spontaneous circulation. The co-primary endpoint is feasibility, defined as the initiation of treatment within the inclusion window in more than 90 % of participants, and efficacy, defined as the area under the neuron-specific enolase curve from 0 to 72 hours after admission. Secondary endpoints include all-cause mortality at 30 days and Cerebral Performance Category as well as a modified Rankin Score at 180 days. The study has been approved by the Danish National Board of Health and the local Ethics Committee and is monitored by Good Clinical Practice units. The study is currently enrolling. Discussion This paper presents the methods and planned statistical analyses used in the GLP-1 trial and aims to minimize bias and data-driven reporting of results. Trial registration 1) Danish National Board of Health, EudraCT 2013-004311-45. Registered on 25 March 2014. 2) Videnskabsetisk komité C, Region Hovedstaden, No. 45728. Registered on 29 January 2014. 3) Clinicaltrial.gov, NCT02442791. Registered on 25 of January 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1421-2) contains supplementary material, which is available to authorized users.

Acute STEMI is routinely treated by acute PCI. This treatment may itself damage the tissue (reperfusion injury). Conditioning with GLP-1 analogs has been shown to reduce reperfusion injury. Likewise, ischemic postconditioning provides cardioprotection following STEMI. We tested if combined conditioning with the GLP-1 analog liraglutide and ischemic postconditioning offered additive cardioprotective effect after reperfusion of 45 min coronary occlusion of left anterior descending artery (LAD).Fifty-eight non-diabetic female Danish Landrace pigs (60 ± 10kg) were randomly assigned to four groups. Myocardial infarction (MI) was induced by occluding the LAD for 45 min. Group 1 (n = 14) was treated with i.v. liraglutide after 15 min of ischemia. Group 2 (n = 17) received liraglutide treatment concomitant with ischemic postconditioning, after 45 min of ischemia. Group 3 (n = 15) recieved ischemic postconditioning and group 4 (n = 12) was kept as controls.No intergroup differences in relative infarct size were detected (overall mean 57 ± 3%; p = 0.68). Overall mortality was 34% (CI 25-41%) including 26% post-intervention, with no intergroup differences (p = 0.99). Occurrence of ventricular fibrillation (VF) was 59% (CI 25-80%) including 39% postintervention with no intergroup differences (p = 0.65).In our closed-chest pig-model, we were unable to detect any cardioprotective effect of liraglutide or ischemic postconditioning either alone or combined.

Ischaemic heart disease (IHD) remains the leading cause of death and disability in Europe and worldwide. A major cause of morbidity and mortality in IHD patients is an acute ST-segment elevation myocardial infarction (STEMI), which despite prompt reperfusion by primary percutaneous coronary intervention (PPCI) has significant mortality (7% death at 1 year) and morbidity (22% prolonged or new hospitalization for heart failure at 1 year) in patients with large infarcts.1 When high-risk STEMI patients presenting with cardiogenic shock are not excluded, mortality at 1 year is even higher, at 12% after 1 year.2 As such, there remains an urgent need to discover novel therapies which can be given prior to or at the time of PPCI to reduce myocardial infarct (MI) size in order to preserve left ventricular (LV) systolic function, prevent the onset of heart failure, and improve survival in reperfused STEMI patients. In patients presenting with STEMI, rapid access to the emergency medical services and timely reperfusion by PPCI minimize the total ischaemic time, a major determinant of MI size. Although myocardial reperfusion is essential to salvage myocardium following a STEMI, the process of restoring coronary blood flow to the ischaemic tissue can, in itself, induce myocardial injury and cardiomyocyte death, a phenomenon which is known as ‘myocardial reperfusion injury’.3,4 Crucially, there is currently no effective therapy for reducing myocardial reperfusion injury in STEMI patients, and therefore, it remains a valid target for cardioprotection. However, the search for an effective therapy capable of targeting myocardial reperfusion injury and reducing MI size has been quite challenging, with a large number of failures to translate novel cardioprotective therapies into the …

Determining infarct size and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) is important when assessing the efficacy of new reperfusion strategies. We investigated whether restTwelve STEMI patients were injected withSPECT, CMR, and PET were performed 2.2 ± 0.5, 34 ± 8.5, and 32 ± 24.4 h after reperfusion, respectively. Mean (± SD) area at risk were 35.2 ± 16.6%, 34.7 ± 11.3%, and 28.1 ± 16.1% of the left ventricle (LV) in SPECT, CMR, and PET, respectively, P = 0.04 for difference. Mean final infarct size estimates were 12.3 ± 15.4%, 13.7 ± 10.4%, and 11.9 ± 14.6% of the LV in SPECT, CMR, and PET imaging, respectively, P = .72. Myocardial salvage indices were 0.64 ± 0.33 (SPECT), 0.65 ± 0.20 (CMR), and 0.63 ± 0.28 (PET), (P = .78).

Aims Our aim was to investigate the strength of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) in daily practice. Methods and results For this study, 3,512 patients with stable CAD and at least one 50-89% coronary stenosis were identified; those patients thought to require PCI (n=1,716) were selected. Of these, 962 (56%) were treated based on angiography (XA) alone, whereas 754 patients (44%) had an FFR-guided treatment. In the latter group, 321 patients (43%) were reallocated to another treatment, predominantly medical treatment. After propensity score matching, the number of indicated lesions was 957 in the XA-guided group and 947 in the FFR-guided group. FFR guidance resulted in PCI deferral in 462 lesions (48.8%). In a seven-day landmark analysis, the rate of periprocedural myocardial infarction (MI) was less than half in the FFR-guided group (p>0.05). For the eight-day to four-year follow-up period, FFR guidance resulted in a significantly lower rate of the combined endpoint of death/MI (hazard ratio [HR] 0.63) and MI-driven target lesion revascularisation (HR 0.35). Conclusions This large, retrospective study shows that performing FFR has a significant impact on therapeutic strategy and demonstrates the favourable long-term outcome of FFR-guided PCI in an "all-comers" population of patients with stable CAD in daily clinical practice.

Despite its high prevalence among patients suffering myocardial infarction, the significance of left ventricle hypertrophy for infarct size is not known. We asked whether infarct size might be increased by this condition, and whether any such increase might be associated with an increased mitochondrial damage following coronary occlusion.Occlusion of the left descending artery in isolated, perfused hearts of SHR-SP (spontaneously hypertensive rat stroke-prone) (left ventricular hypertrophy) or Wistar-Kyoto (WKY) (control) rats was used, followed by reperfusion with or without exendin-4 (Exe-4), a glucagon-like peptide-1 receptor agonist. Infarct size relative to area-at-risk was determined. Separately, mitochondria were isolated after global ischemia. Activities of complexes III and IV and amounts of selected complex subunits and cytochromes a, b, c, and c1 were determined.Infarct size (ischemia 35 min and 120 min reperfusion) was 65.8% (±3.3%) and 37.1% (±3.4%) in the SHR-SP and WKY hearts, respectively (P 0.05). Exe-4 significantly decreased infarct size and hypercontracture in WKY, but not in SHR-SP, hearts. After ischemia 15 min in SHR-SP hearts, Exe-4 reduced the infarct (26.6%, ±3.8% to 9.3% ± 1.5%; P 0.05). Mitochondria from postischemic SHR-SP hearts showed a reduction of complex III (368.1 ± 37.5 to 175.8 ± 23.0 nmoles/min × mg; P 0.05) and complex IV (14.4 ± 0.22 to 5.8 ± 0.8 1/s × mg; P 0.05) activities and decreased amounts of cytochromes a, b, and c.Hearts from hypertensive (SHR-SP) rats with left ventricle hypertrophy appeared more vulnerable to ischemia-reperfusion injury, as supported by a more profound infarct development and an earlier loss of postconditioning by Exe-4. Mitochondrial complexes III and IV were identified among possible loci of this increased, hypertrophy-associated vulnerability.

There are limited data to guide the optimum approach to patients presenting with angina after coronary artery bypass grafting (CABG). Although often referred for invasive angiography, the effectiveness of this is unknown; angina may also result from diffuse distal or micro-vascular coronary disease and it is not known how often targets for intervention are identified.Retrospective review of 50,460 patients undergoing angiography in East Denmark between January 2010 and December 2014. Clinical and procedural data were prospectively stored in a regional electronic database. Follow-up data were available for all patients, by means of records linked to each Danish social security number.In patients with prior CABG and stable angina (n = 2,309), diagnostic angiography led to revascularization in 574 (24.9%) cases. Chronic kidney disease (HR 1.93 [1.08-3.44], P = 0.027), significant angina (HR 1.49 [1.18-1.88], P = 0.006 for angina class ≥ II, and HR 2.04 [1.61-2.58], P 0.001 for angina class ≥ III) and a positive pre-procedural stress test (HR 2.56 [1.42-4.60], P 0.001) were independent predictors of revascularization. Stress testing was, however, used less frequently than in patients without prior CABG (17.2% vs. 24.2%, P 0.001). The positive predictive values for subsequent revascularization were 47.8%, 51.4%, and 66.9% for exercise ECG, stress echocardiography, and myocardial perfusion scintigraphy (MPS), respectively.Invasive angiography leads to revascularization in a quarter of patients with angina and prior CABG; the threshold for referral may be too low. Non-invasive stress testing predicts the need for revascularization but appears underused and MPS, in particular, may better identify patients likely to require revascularization. © 2016 Wiley Periodicals, Inc.

PURPOSE: β2-Agonists are widely used for relief of respiratory symptoms. Studies so far have reported conflicting results regarding use of β2-agonists and risk of myocardial infarction (MI). Yet, coronary angiographical data and longitudinal outcomes data are sparse and could help explain if there is an association between use of β2-agonists and MI.METHODS: Using a novel data-linkage of the Eastern Danish Heart Registry and nationwide administrative registries we identified a cohort of patients referred for acute coronary angiography due to ST-elevation MI (STEMI). Clinical and angiographical findings were compared between β2-agonist users and non-users.RESULTS: Among 66,234 patients undergoing coronary angiography, 9857 patients had STEMI. Of these, 933 (9%) patients used β2-agonists. β2-Agonist users were more often without significant coronary stenosis (15% in β2-agonist users vs 9% in non-users; pCONCLUSION: Among patients referred to urgent coronary angiography for STEMI, use of β2-agonists was associated with a lower frequency of significant coronary stenosis and a higher mortality compared with non-users.

Pulmonary hyperinflation is used by competitive breath-hold divers and is accomplished by glossopharyngeal insufflation (GPI), which is known to compress the heart and pulmonary vessels, increasing sympathetic activity and lowering cardiac output (CO) without known consequence for organ perfusion. Myocardial, pulmonary, skeletal muscle, kidney, and liver perfusion were evaluated by magnetic resonance imaging in 10 elite breath-hold divers at rest and during moderate GPI. Cardiac chamber volumes, stroke volume, and thus CO were determined from cardiac short-axis cine images. Organ volumes were assessed from gradient echo sequences, and organ perfusion was evaluated from first-pass images after gadolinium injection. During GPI, lung volume increased by 5.2 ± 1.5 liters (mean ± SD; P < 0.001), while spleen and liver volume decreased by 46 ± 39 and 210 ± 160 ml, respectively ( P < 0.05), and inferior caval vein diameter by 4 ± 3 mm ( P < 0.05). Heart rate tended to increase (67 ± 10 to 86 ± 20 beats/min; P = 0.052) as right and left ventricular volumes were reduced ( P < 0.05). Stroke volume (107 ± 21 to 53 ± 15 ml) and CO (7.2 ± 1.6 to 4.2 ± 0.8 l/min) decreased as assessed after 1 min of GPI ( P < 0.01). Left ventricular myocardial perfusion maximum upslope and its perfusion index decreased by 1.52 ± 0.15 s−1 ( P < 0.001) and 0.02 ± 0.01 s−1 ( P < 0.05), respectively, without transmural differences. Pulmonary tissue, spleen, kidney, and pectoral-muscle perfusion also decreased ( P < 0.05), and yet liver perfusion was maintained. Thus, during pulmonary hyperinflation by GPI, CO and organ perfusion, including the myocardium, as well as perfusion of skeletal muscles, are reduced, and yet perfusion of the liver is maintained. Liver perfusion seems to be prioritized when CO decreases during GPI.

AIMS: The aim of this study was to evaluate whether a staged in-hospital complete revascularisation strategy increases the risk of serious bleeding events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease.METHODS AND RESULTS: The DANAMI-3-PRIMULTI trial investigated whether a staged in-hospital complete revascularisation strategy improved outcome in patients with STEMI and multivessel disease. In this substudy, we investigated potential bleeding complications related to a second in-hospital procedure. Bleedings were assessed using BARC and TIMI criteria. Six hundred and twenty-seven (627) patients were randomised 1:1 to either PCI of the infarct-related artery (IRA) only (n=313) or complete revascularisation during a staged procedure before discharge (n=314). We found no significant difference in TIMI major+minor bleedings related to the primary PCI. There were neither major nor minor bleedings in relation to the second procedure in the complete revascularisation arm. There were significantly more in-hospital minimal+medical attention bleedings in the group randomised to complete revascularisation (61.5% vs. 49.5% in the IRA-PCI only group, p=0.003), but no difference in admission time or one-year mortality (2.2% complete revascularisation-group vs. 2.6% IRA-PCI only group, p=0.8).CONCLUSIONS: In multivessel diseased STEMI patients, a staged complete in-hospital revascularisation strategy or any second in-hospital procedure did not result in an increase in serious bleeding events.

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).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, and180 minutes).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, and180 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).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.

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.Global ischemia (35 min)-reperfusion (120 min) was applied in isolated, retrogradely perfused rat hearts. Peptides were present for 15 min 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.Curaglutide did not affect any of the functional heart parameters when administered without preceding ischemia. Curaglutide 0.3 nM 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; P0.05). 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).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.

Background— The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize all-comers with severe native aortic valve stenosis to either transcatheter aortic valve replacement (TAVR) with the CoreValve self-expanding bioprosthesis or surgical aortic valve replacement (SAVR), including a lower-risk patient population than previous trials. This article reports 2-year clinical and echocardiographic outcomes from the NOTION trial. Methods and Results— Two-hundred eighty patients from 3 centers in Denmark and Sweden were randomized to either TAVR (n=145) or SAVR (n=135) with follow-up planned for 5 years. There was no difference in all-cause mortality at 2 years between TAVR and SAVR (8.0% versus 9.8%, respectively; P =0.54) or cardiovascular mortality (6.5% versus 9.1%; P =0.40). The composite outcome of all-cause mortality, stroke, or myocardial infarction was also similar (15.8% versus 18.8%, P =0.43). Forward-flow hemodynamics were improved following both procedures, with effective orifice area significantly more improved after TAVR than SAVR (effective orifice area, 1.7 versus 1.4 cm 2 at 3 months). Mean valve gradients were similar after TAVR and SAVR. When patients were categorized according to Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) (P =0.58) or intermediate-risk patients (21.1% versus 27.1%; P =0.59). Conclusions— Two-year results from the NOTION trial demonstrate the continuing safety and effectiveness of TAVR in lower-risk patients. Longer-term data are needed to verify the durability of this procedure in this patient population. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01057173.

Summary Background In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up. Methods The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774. Findings After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75–1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p Interpretation The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients. Funding St Jude Medical, Friends of the Heart Foundation, and Medtronic.

Background In patients with ST-segment elevation myocardial infarction (STEMI) pre-infarction angina, pre-procedural TIMI flow and collateral flow to the myocardium supplied by the infarct related artery are suggested to be cardioprotective. We evaluated the effect of these factors on myocardial salvage index (MSI) and infarct size adjusting for area at risk in patients with STEMI treated with primary percutaneous coronary intervention. Methods and Results Cardiac magnetic resonance (CMR) was used to measure myocardial area at risk within 1-7 days and final infarct size 90±21 days after the STEMI in 200 patients. MSI was calculated as (area-at-risk infarct size) / area-at-risk. Patients with pre-infarction angina had a median MSI of 0.80 (IQR 0.67 to 0.86) versus 0.72 (0.61 to 0.80) in those without pre-infarction angina, P = 0.004). In a regression analysis of the infarct size plotted against the area-at-risk there was a strong trend that the line for the pre-infarction angina group was below the one for the non-angina group ( P = 0.05). Patients with pre-procedural TIMI flow 0/1, 2 and 3 had a median MSI of (0.69 (IQR 0.59 to 0.76), 0.78 (0.68 to 0.86) and 0.85 (0.77 to 0.91), respectively ( P

It is unknown whether high-sensitivity C-reactive protein (hs-CRP) predicts outcome depending on implanted stent type. We investigated the prognostic value of hs-CRP in relation to type of stent implanted in patients with ST-segment elevation myocardial infarction (STEMI). Immediately before primary percutaneous coronary intervention (pPCI), 301 patients had blood drawn. Patients were categorized according to hs-CRP levels and combination of hs-CRP (≤2 vs >2 mg/L) and stent type (bare metal stent [BMS] vs drug-eluting stent [DES]). Hs-CRP >2 mg/L (median, hazard ratio 2.7, 95% confidence interval 1.3 to 5.6, p = 0.007) and the combined variable of hs-CRP >2 mg/L and BMS (hazard ratio 2.4, 95% confidence interval 1.2 to 4.5, p = 0.006) independently predicted the composite end point of death and MI at 36-month follow-up. There was a significant interaction (p = 0.006) for hs-CRP and stent type. Survival analysis demonstrated significant differences for occurrence of death and MI: 4.8% in BMS + CRP ≤2 mg/L, 11.9% in DES + CRP ≤2 mg/L, 17.6% in DES + CRP >2 mg/L, and 27.9% in BMS + CRP >2 mg/L. None of the 14 stent thromboses occurred in patients with BMS + CRP ≤2 mg/L. In conclusion, preprocedure hs-CRP predicts outcome after pPCI in patients with STEMI. Our hypothesis-generating data indicate that BMS implantation should be preferred when hs-CRP is ≤2 mg/L and DES when hs-CRP is >2 mg/L to decrease long-term adverse outcomes including stent thrombosis in patients with STEMI treated with pPCI. These findings need confirmation in larger randomized clinical trials.

Objectives The purpose of this study was to compare long-term clinical outcomes after implantation of drug-eluting stents (DES) and bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). Background The evidence of long-term efficacy and safety after implantation of DES in patients with complex lesions is scarce. Methods We randomly assigned 626 patients with STEMI referred within 12 h to have a DES or a BMS implanted in the infarct-related lesion with or without distal protection during primary percutaneous coronary intervention. Results At 3 years, target lesion revascularization was 6.1% in the DES group compared with 16.3% in the BMS group (p Conclusions Implantation of DES in patients with STEMI reduces the long-term rate of major adverse cardiac events compared with BMS, but patients with DES had a higher risk of cardiac death not attributed to myocardial infarction or stent thrombosis. (Drug Elution and Distal Protection During Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction [DEDICATION]; NCT00192868 )

Primary percutaneous coronary intervention is the recommended therapy for patients with ST‑elevation myocardial infarction. However, restoration of coronary blood flow may lead to reperfusion injury, which has been suggested to account for 50% of the final myocardial infarct size. As an adjuvant therapy to primary percutaneous coronary intervention, ischemic postconditioning (IPost) has been shown to be safe and to underlie cardioprotection in several clinical trials. However, there remain important issues to be settled before IPost can be used routinely in patients undergoing primary percutaneous coronary intervention: first, determining which IPost protocol is the most optimal in humans; second, determining the effect of IPost on clinical outcome; third, determining in which patients should IPost be applied; and fourth, determining the effect on left ventricular function. This article discusses these issues with a clinical perspective and looks into alternative pharmacological cardioprotection.

Objectives The purpose of this study was to investigate the 2-year outcome of percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) in patients with multivessel coronary artery disease (CAD). Background In patients with multivessel CAD undergoing PCI, coronary angiography is the standard method for guiding stent placement. The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study showed that routine FFR in addition to angiography improves outcomes of PCI at 1 year. It is unknown if these favorable results are maintained at 2 years of follow-up. Methods At 20 U.S. and European medical centers, 1,005 patients with multivessel CAD were randomly assigned to PCI with drug-eluting stents guided by angiography alone or guided by FFR measurements. Before randomization, lesions requiring PCI were identified based on their angiographic appearance. Patients randomized to angiography-guided PCI underwent stenting of all indicated lesions, whereas those randomized to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was ≤0.80. Results The number of indicated lesions was 2.7 ± 0.9 in the angiography-guided group and 2.8 ± 1.0 in the FFR-guided group (p = 0.34). The number of stents used was 2.7 ± 1.2 and 1.9 ± 1.3, respectively (p 0.80, the rate of myocardial infarction was 0.2 % and the rate of revascularization was 3.2 % after 2 years. Conclusions Routine measurement of FFR in patients with multivessel CAD undergoing PCI with drug-eluting stents significantly reduces mortality and myocardial infarction at 2 years when compared with standard angiography-guided PCI. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774 )

Objectives This retrospective multicenter registry evaluated the safety and feasibility of left ventricular (LV) support with the Impella 2.5 (Abiomed Europe GmbH, Aachen, Germany) during high-risk percutaneous coronary intervention (PCI). Background Patients with complex or high-risk coronary lesions, such as last remaining vessel or left main lesions, are increasingly being treated with PCI. Because periprocedural hemodynamic compromise and complications might occur rapidly, many of these high-risk procedures are being performed with mechanical cardiac assistance, particularly in patients with poor LV function. The Impella 2.5, a percutaneous implantable LV assist device, might be a superior alternative to the traditionally used intra-aortic balloon pump. Methods The Europella registry included 144 consecutive patients who underwent a high-risk PCI. Safety and feasibility end points included incidence of 30-day adverse events and successful device function. Results Patients were older (62% >70 years of age), 54% had an LV ejection fraction ≤30%, and the prevalence of comorbid conditions was high. Mean European System for Cardiac Operative Risk Evaluation score was 8.2 (SD 3.4), and 43% of the patients were refused for coronary artery bypass grafting. A PCI was considered high-risk due to left main disease, last remaining vessel disease, multivessel coronary artery disease, and low LV function in 53%, 17%, 81%, and 35% of the cases, respectively. Mortality at 30 days was 5.5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively. Conclusions This large multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI.

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.

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

Objectives The purpose of this study was to evaluate the use of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in native coronary vessels. Background Embolization of material from the infarct-related lesion during PCI may result in impaired myocardial perfusion and worsen the prognosis. Previous attempts to protect the microcirculation during primary PCI have had conflicting results. Methods We randomly assigned 626 patients with STEMI referred within 12 h to have PCI performed with (n = 312) or without (n = 314) distal protection. The primary end point was complete (≥70%) ST-segment resolution detected by continuous ST-segment monitoring. Blood levels of troponin-T and creatine kinase-MB were monitored before and after the procedure, and echocardiographic determination of the left ventricular wall motion index (WMI) was performed before discharge. Results Patients were well matched in terms of demographic and angiographic baseline characteristics. There was no significant difference in the occurrence of the primary end point (76% vs. 72%, p = 0.29), no difference in maximum troponin-T (4.8 μg/l and 5.0 μg/l, p = 0.87) or maximum creatine kinase-MB (185 μg/l and 184 μg/l, p = 0.99), and no difference in median WMI (1.70 vs. 1.70, p = 0.35). The rate of major adverse cardiac and cerebral events (MACCE) 1 month after PCI was 5.4% with distal protection and 3.2% with conventional treatment (p = 0.17). Conclusions The routine use of distal protection by a filterwire system during primary PCI does not seem to improve microvascular perfusion, limit infarct size, or reduce the occurrence of MACCE (Drug Elution and Distal Protection During Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction; NCT00192868).

The rationale and study design for the multicentre, randomized, controlled CONDI2/ERIC-PPCI study are discussed.

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.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.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.