Influence of intensive lipid-lowering on CT derived fractional flow reserve in patients with stable chest pain: Rationale and design of the FLOWPROMOTE study.

INTRODUCTION: Coronary CT angiography (CTA) derived fractional flow reserve (FFRCT ) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated. AIM: To test whether lipid lowering therapy is associated with significant improvement in FFRCT , and whether there is a dose-response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery. METHODS: Investigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first-line CTA, and FFRCT ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFRCT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18-month difference in FFRCT using (1) the FFRCT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study. CONCLUSION: The results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease.

Nationwide Trends in Cardiac Risk and Mortality in Patients With Incident Type 2 Diabetes: A Danish Cohort Study.

OBJECTIVE: Trends in cardiac risk and death have not been examined in patients with incident type 2 diabetes and no prior cardiovascular disease. Therefore, we aimed to examine trends in cardiac risk and death in relation to the use of prophylactic cardiovascular medications in patients with incident type 2 diabetes without prior cardiovascular disease. RESEARCH DESIGN AND METHODS: In this population-based cohort study, we included patients with incident type 2 diabetes between 1996 and 2011 through national health registries. Each patient was matched by age and sex with up to five individuals without diabetes from the general population. All individuals were followed for 7 years. RESULTS: We identified 209,311 patients with incident diabetes. From 1996-1999 to 2008-2011, the 7-year risk of myocardial infarction decreased from 6.9 to 2.8% (adjusted hazard ratio [aHR] 0.39 [95% CI 0.37-0.42]), cardiac death from 7.1 to 1.6% (aHR 0.23 [95% CI 0.21-0.24]), and all-cause death from 28.9 to 16.8% (aHR 0.68 [95% CI 0.66-0.69]). Compared with the general population, 7-year risk differences decreased from 3.3 to 0.8% for myocardial infarction, from 2.7 to 0.5% for cardiac death, and from 10.6 to 6.0% for all-cause death. Use of cardiovascular medications within ±1 year of diabetes diagnosis, especially statins (5% of users in 1996-1999 vs. 60% in 2008-2011), increased during the study period. CONCLUSIONS: From 1996 to 2011, Danish patients with incident type 2 diabetes and no prior cardiovascular disease experienced major reductions in cardiac risk and mortality. The risk reductions coincided with increased use of prophylactic cardiovascular medications.

Reduction of Myocardial Infarction and All-Cause Mortality Associated to Statins in Patients Without Obstructive CAD.

OBJECTIVES: The aim of this work was to evaluate the prognostic impact of statin therapy in symptomatic patients without obstructive CAD. BACKGROUND: Information on the prognostic impact of post-coronary computed tomographic angiography (CTA) statin use in patients with no or nonobstructive coronary artery disease (CAD) is sparse. METHODS: Patients undergoing CTA with suspected CAD in western Denmark from 2008 to 2017 with <50% coronary stenoses were identified. Information on post-CTA use of statin therapy and cardiovascular events were obtained from national registries. RESULTS: The study included 33,552 patients, median aged 56 years, 58% female, with no (n = 19,669) or nonobstructive (n = 13,883) CAD and a median follow-up of 3.5 years. The absolute risk of the combined end point of myocardial infarction (MI) or all-cause mortality was directly associated with the CAD burden with an event rate/1,000 patient-years of 4.13 (95% CI: 3.69-4.61) in no, 7.74 (95% CI: 6.88-8.71) in mild (coronary artery calcium score [CACS] 0-99), 13.72 (95% CI: 11.61-16.23) in moderate (CACS 100-399), and 32.47 (95% CI: 26.25-40.16) in severe (CACS ≥400) nonobstructive CAD. Statin therapy was associated with a multivariable adjusted HR for MI and death of 0.52 (95% CI: 0.36-0.75) in no, 0.44 (95% CI: 0.32-0.62) in mild, 0.51 (95% CI: 0.34-0.75) in moderate, and 0.52 (95% CI: 0.32-0.86) in severe nonobstructive CAD. The estimated numbers needed to treat to prevent the primary end point were 92 (95% CI: 61-182) in no, 36 (95% CI: 26-58) in mild, 24 (95% CI: 15-61) in moderate, and 13 (95% CI: 7-86) in severe nonobstructive CAD. Residual confounding may persist, but not to an extent explaining all of the observed risk reduction associated with statin treatment. CONCLUSIONS: The risk of MI and all-cause mortality in patients without obstructive CAD is directly associated with the CAD burden. Statin therapy is associated with a reduction of MI and all-cause death across the spectrum of CAD, however, the absolute benefit of treatment is directionally proportional with the CAD burden.

Improving translational research in sex-specific effects of comorbidities and risk factors in ischaemic heart disease and cardioprotection: position paper and recommendations of the ESC Working Group on Cellular Biology of the Heart.

Ischaemic heart disease (IHD) is a complex disorder and a leading cause of death and morbidity in both men and women. Sex, however, affects several aspects of IHD, including pathophysiology, incidence, clinical presentation, diagnosis as well as treatment and outcome. Several diseases or risk factors frequently associated with IHD can modify cellular signalling cascades, thus affecting ischaemia/reperfusion injury as well as responses to cardioprotective interventions. Importantly, the prevalence and impact of risk factors and several comorbidities differ between males and females, and their effects on IHD development and prognosis might differ according to sex. The cellular and molecular mechanisms underlying these differences are still poorly understood, and their identification might have important translational implications in the prediction or prevention of risk of IHD in men and women. Despite this, most experimental studies on IHD are still undertaken in animal models in the absence of risk factors and comorbidities, and assessment of potential sex-specific differences are largely missing. This ESC WG Position Paper will discuss: (i) the importance of sex as a biological variable in cardiovascular research, (ii) major biological mechanisms underlying sex-related differences relevant to IHD risk factors and comorbidities, (iii) prospects and pitfalls of preclinical models to investigate these associations, and finally (iv) will provide recommendations to guide future research. Although gender differences also affect IHD risk in the clinical setting, they will not be discussed in detail here.

Association of Neighborhood Disadvantage With Cardiovascular Risk Factors and Events Among Refugees in Denmark.

Importance: Refugees are among the most disadvantaged individuals in society, and they often have elevated risks of cardiovascular risk factors and events. Evidence is limited regarding factors that may worsen cardiovascular health among this vulnerable group. Objective: To test the hypothesis that refugee placement in socioeconomically disadvantaged neighborhoods is associated with increased cardiovascular risk. Design, Setting, and Participants: The study population of this quasi-experimental, registry-based cohort study included 49 305 adults 18 years and older who came to Denmark as refugees from other countries during the years of Denmark's refugee dispersal policy from 1986 to 1998. Refugees were dispersed to neighborhoods with varying degrees of socioeconomic disadvantage in an arbitrary manner conditional on observed characteristics. The association of neighborhood disadvantage on arrival with several cardiovascular outcomes in subsequent decades was evaluated using regression models that adjusted for individual, family, and municipal characteristics. Health outcomes were abstracted from the inpatient register, outpatient specialty clinic register, and prescription drug register through 2016. Data analysis was conducted from May 2018 to July 2019. Exposures: A composite index of neighborhood disadvantage was constructed using 8 neighborhood-level socioeconomic characteristics derived from Danish population register data. Main Outcomes and Measures: Primary study outcomes included hypertension, hyperlipidemia, type 2 diabetes, myocardial infarction, and stroke. Before data analysis commenced, it was hypothesized that higher levels of neighborhood disadvantage were associated with an increased risk of cardiovascular risk factors and events. Results: A total of 49 305 participants were included (median [interquartile range] age, 30.5 [24.9-39.8] years; 43.3% women). Participant region of origin included 6318 from Africa (12.8%), 7253 from Asia (14.7%), 3446 from Eastern Europe (7.0%), 5416 from Iraq (11.0%), 6206 from Iran (12.6%), 5558 from Palestine (via Lebanon, Israel, Occupied Palestinian Territories; 11.3%), and 15 108 from Yugoslavia (30.6%). Adjusted models revealed an association between placement in disadvantaged neighborhoods and increased risk of hypertension (0.71 [95% CI, 0.30-1.13] percentage points per unit of disadvantage index; P < .01), hyperlipidemia (0.44 [95% CI, 0.06-0.83] percentage points; P = .01), diabetes (0.45 [95% CI, 0.09-0.81] percentage points; P = .01), and myocardial infarction (0.14 [95% CI, 0.03-0.25] percentage points; P = .01). No association was found for stroke. Individuals who arrived in Denmark before age 35 years had an increased risk of hyperlipidemia (1.16 [95% CI, 0.41-1.92] percentage points; P < .01), and there were no differences by sex. Conclusions and Relevance: In this quasi-experimental cohort study, neighborhood disadvantage was associated with increased cardiovascular risk in a relatively young population of refugees. Neighborhood characteristics may be an important consideration when refugees are placed by resettlement agencies and host countries. Future work should examine additional health outcomes as well as potential mediating pathways to target future interventions (eg, neighborhood ease of walking, employment opportunities).

Diabetes is not a risk factor for myocardial infarction in patients without coronary artery disease: A study from the Western Denmark Heart Registry.

BACKGROUND: Diabetes is considered a risk factor for myocardial infarction. However, we have previously found that diabetes was not a short-term risk factor for myocardial infarction in the absence of obstructive coronary artery disease. METHODS: We conducted a cohort study of patients undergoing coronary angiography from 2003 to 2012 and followed them by cross-linking Danish health registries. Patients were stratified according to coronary artery disease and diabetes. Endpoints included myocardial infarction, cardiac death, all-cause death and coronary revascularization. RESULTS: 86,202 patients were included in total (diabetes: n = 12,652). Median follow-up was 8.8 years. Using patients with neither coronary artery disease nor diabetes as reference (cumulative myocardial infarction incidence 2.6%), the risk of myocardial infarction was low and not substantially increased for patients with diabetes alone (3.2%; hazard ratio 1.202, 95% confidence interval 0.996-1.451), was increased for patients with coronary artery disease alone (9.3%; hazard ratio 2.75, 95% confidence interval 2.52-3.01) and was highest for patients with both coronary artery disease and diabetes (12.3%; hazard ratio 3.79, 95% confidence interval 3.43-4.20). Similar associations were observed for cardiac death and coronary revascularization. CONCLUSION: Diabetes patients without coronary artery disease by coronary angiography have a low risk of myocardial infarction, not substantially increased compared to patients with neither coronary artery disease nor diabetes. In the presence of coronary artery disease, however, diabetes increases the risk of myocardial infarction.

Remote ischemic conditioning in active ulcerative colitis: An explorative randomized clinical trial.

Remote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury. The protection is partly through down-regulation of the inflammatory response. Our aim was to investigate the clinical and anti-inflammatory effects of RIC in patients with active ulcerative colitis (UC). We included 22 patients with active UC in this explorative, randomized, sham-controlled clinical trial. The patients were randomly assigned 1:1 to RIC (induced in the arm through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff) or sham (incomplete inflation of the blood-pressure cuff) once daily for 10 days. Outcome variables were measured at baseline and on day 11. When compared with sham, RIC did not affect inflammation in the UC patients measured by fecal calprotectin, plasma C-reactive protein, Mayo Score, Mayo Endoscopic Subscore, Nancy Histological Index or inflammatory cytokines involved in UC and RIC. The mRNA and miRNA expression profiles in the UC patients were measured by RNA sequencing and multiplexed hybridization, respectively, but were not significantly affected by RIC. We used the Langendorff heart model to assess activation of the organ protective mechanism induced by RIC, but could not confirm activation of the organ protective mechanism in the UC patients.

Aortic Calcification Affects Noninvasive Estimates of Central Blood Pressure in Patients with Severe Chronic Kidney Disease.

BACKGROUND: Central blood pressure (BP) assessed noninvasively considerably underestimates true invasively measured aortic BP in chronic kidney disease (CKD) patients. The difference between the estimated and the true aortic BP increases with decreasing estimated glomerular filtration rates (eGFR). The present study investigated whether aortic calcification affects noninvasive estimates of central BP. METHODS: Twenty-four patients with CKD stage 4-5 undergoing coronary angiography and an aortic computed tomography scan were included (63% males, age [mean ± SD ] 53 ± 11 years, and eGFR 9 ± 5 mL/min/1.73 m2). Invasive aortic BP was measured through the angiography catheter, while non-invasive central BP was obtained using radial artery tonometry with a SphygmoCor® device. The Agatston calcium score (CS) in the aorta was quantified on CT scans using the CS on CT scans. RESULTS: The invasive aortic systolic BP (SBP) was 152 ± 23 mm Hg, while the estimated central SBP was 133 ± 20 mm Hg. Ten patients had a CS of 0 in the aorta, while 14 patients had a CS >0 in the aorta. The estimated central SBP was lower than the invasive aortic SBP in patients with aortic calcification compared to patients without (mean difference 8 mm Hg, 95% CI 0.3-16; p = 0.04). The brachial SBP was lower than the aortic SBP in patients with aortic calcification compared to patients without (mean difference 10 mm Hg, 95% CI 2-19; p = 0.02). CONCLUSION: In patients with advanced CKD the presence of aortic calcification is associated with a higher difference between invasively measured central aortic BP and non-invasive estimates of central BP as compared to patients without calcifications.

Predictive value of routine point-of-care cardiac troponin T measurement for prehospital diagnosis and risk-stratification in patients with suspected acute myocardial infarction.

OBJECTIVE: The purpose of this study was to determine the predictive value of routine prehospital point-of-care cardiac troponin T measurement for diagnosis and risk stratification of patients with suspected acute myocardial infarction. METHODS AND RESULTS: All prehospital emergency medical service vehicles in the Central Denmark Region were equipped with a point-of-care cardiac troponin T device (Roche Cobas h232) for routine use in all patients with a suspected acute myocardial infarction. During the study period, 1 June 2012-30 November 2015, prehospital point-of-care cardiac troponin T measurements were performed in a total of 19,615 cases seen by the emergency medical service and 18,712 point-of-care cardiac troponin T measurements in 15,781 individuals were matched with an admission. A final diagnosis of acute myocardial infarction was confirmed in 2187 cases and a total of 2150 point-of-care cardiac troponin T measurements (11.0%) had a value ≥50 ng/l, including 966 with acute myocardial infarction (sensitivity: 44.2%, specificity: 92.8%). Patients presenting with a prehospital point-of-care cardiac troponin T value ≥50 ng/l had a one-year mortality of 24% compared with 4.8% in those with values <50 ng/l, log-rank: p<0.001. The following variables showed the strongest association with mortality in multivariable analysis: point-of-care cardiac troponin T≥50 ng/l (hazard ratio 2.10, 95% confidence interval: 1.90-2.33), congestive heart failure (hazard ratio 1.93, 95% confidence interval: 1.74-2.14), diabetes mellitus (hazard ratio 1.42, 95% confidence interval: 1.27-1.59) and age, one-year increase (hazard ratio 1.08, 95% confidence interval: 1.08-1.09). CONCLUSIONS: Patients with suspected acute myocardial infarction and a prehospital point-of-care cardiac troponin T ≥50 ng/l have a poor prognosis irrespective of the final diagnosis. Routine troponin measurement in the prehospital setting has a high predictive value and can be used to identify high-risk patients even before hospital arrival so that they may be re-routed directly for advanced care at an invasive centre.

Enhancing and Extending Biological Performance and Resilience.

Human performance, endurance, and resilience have biological limits that are genetically and epigenetically predetermined but perhaps not yet optimized. There are few systematic, rigorous studies on how to raise these limits and reach the true maxima. Achieving this goal might accelerate translation of the theoretical concepts of conditioning, hormesis, and stress adaptation into technological advancements. In 2017, an Air Force-sponsored conference was held at the University of Massachusetts for discipline experts to display data showing that the amplitude and duration of biological performance might be magnified and to discuss whether there might be harmful consequences of exceeding typical maxima. The charge of the workshop was "to examine and discuss and, if possible, recommend approaches to control and exploit endogenous defense mechanisms to enhance the structure and function of biological tissues." The goal of this white paper is to fulfill and extend this workshop charge. First, a few of the established methods to exploit endogenous defense mechanisms are described, based on workshop presentations. Next, the white paper accomplishes the following goals to provide: (1) synthesis and critical analysis of concepts across some of the published work on endogenous defenses, (2) generation of new ideas on augmenting biological performance and resilience, and (3) specific recommendations for researchers to not only examine a wider range of stimulus doses but to also systematically modify the temporal dimension in stimulus inputs (timing, number, frequency, and duration of exposures) and in measurement outputs (interval until assay end point, and lifespan). Thus, a path forward is proposed for researchers hoping to optimize protocols that support human health and longevity, whether in civilians, soldiers, athletes, or the elderly patients. The long-term goal of these specific recommendations is to accelerate the discovery of practical methods to conquer what were once considered intractable constraints on performance maxima.

CT-based total vessel plaque analyses improves prediction of hemodynamic significance lesions as assessed by fractional flow reserve in patients with stable angina pectoris.

BACKGROUND: Coronary stenosis and plaque evaluation by coronary computed tomography angiography (CTA) may contribute to identify hemodynamically relevant lesions. We evaluated the most stenotic lesion including plaques proximal to it versus a total vessel analyses combined with stenosis for ischemia. METHODS: Patients scheduled for clinically indicated invasive coronary angiography (ICA) for suspected coronary artery disease underwent coronary CTA and ICA including fractional flow reserve (FFR) as part of the NXT trial (clinicaltrials.govNCT01757678). Stenoses were visually graded ≤50%, 51-70%, and >70% on coronary CTA. Semi-automated plaque analyses were performed using a proximal to the FFR pressure sensor location (including the most severe lesion to the coronary ostium) versus a total vessel (vessel diameter ≥2 mm) approach. Coronary stenosis and plaque parameters were evaluated for discrimination of ischemia by logistic regressions and combined models analyzed using receiver operating characteristics (ROC) with invasive FFR≤ 0.80 as reference standard. RESULTS: In 254 patients, mean (±SD) age 64 (±10) years, 64% male, a coronary CTA stenosis >50% was present in 239 (49%) vessels. Invasive FFR was ≤0.80 in 100 (21%) vessels. Coronary stenosis severity and low-density non-calcified plaque (LD-NCP) volume were independent predictors of ischemia in the "proximal" and "total-vessel" analyses. Stenosis severity + total vessel LD-NCP assessment performed better than stenosis severity + proximal LD-NCP evaluation (Area under curve [AUC] (95%CI): 0.83 (0.78-0.87) vs 0.81 (0.76-0.86), p-value = 0.009), whereas stenosis severity + proximal LD-NCP performed better than stenosis alone (AUC (95%CI): 0.81 (0.76-0.86) vs 0.78 (0.73-0.83), p-value = 0.019). CONCLUSION: Adding total vessel high-risk plaque volume to stenosis severity improves discrimination of ischemia in coronary CTA performed in patients with stable angina pectoris.

Randomized clinical comparison of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent with the sirolimus-eluting Orsiro stent in patients treated with percutaneous coronary intervention: Rationale and study design of the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X trial.

BACKGROUND: The Combo stent (OrbusNeich, Hoevelaken, the Netherlands) combining an abluminal, bioabsorbable polymer eluting sirolimus with a luminal CD34+ antibody to capture endothelial progenitor cells has been developed to further improve safety and efficacy of coronary interventions. We have designed a large-scale registry-based randomized clinical trial to compare the Combo stent to the Orsiro stent (Biotronik, Bülach, Switzerland) in patients undergoing percutaneous coronary intervention. METHODS: The SORT OUT X study will randomly assign 3,140 patients to treatment with Combo or Orsiro stents at 3 sites in Western Denmark. Patients are eligible if they are ≥18 years old, have chronic stable coronary artery disease or acute coronary syndromes, and have ≥1 coronary lesion with >50% diameter stenosis requiring treatment with a drug-eluting stent. 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 will be derived from validated Danish registries. An event rate of 4.2% is assumed in each stent group. With a sample size of 1,570 patients in each treatment arm, a 2-group large-sample normal approximation test of proportions with a 1-sided 5% significance level will have 90% power to detect noninferiority of the Combo stent compared with the Orsiro stent with a predetermined noninferiority margin of 2.1%. CONCLUSION: The SORT OUT X trial will determine whether the dual-therapy Combo stent is noninferior to the Orsiro stent with respect to clinically driven events (ClinicalTrials.govNCT03216733).

Effects of renal denervation on coronary flow reserve and forearm dilation capacity in patients with treatment-resistant hypertension. A randomized, double-blinded, sham-controlled clinical trial.

BACKGROUND: Microvascular impairment is well documented in hypertension. We investigated the effect of renal sympathetic denervation (RDN) on cardiac and peripheral microvasculature in patients with treatment-resistant essential hypertension (TRH). METHODS: A randomized, single centre, double-blinded, sham-controlled clinical trial. Fifty-eight patients with TRH (ambulatory systolic BP (ASBP) ≥ 145mmHg) despite stable treatment were randomized to RDN or SHAM. RDN was performed with the unipolar Medtronic Flex catheter. Coronary flow reserve (CFR) and coronary- and forearm minimum vascular resistance (C-Rmin and F-Rmin) were determined using transthoracic Doppler echocardiography and F-Rmin with venous occlusion plethysmography at baseline and at six-months follow-up. RESULTS: RDN was performed with 5.3±0.2 lesions in the right renal artery and 5.4±0.2 lesions in the left. Baseline ASBP was 152±2mmHg (RDN, n=29) and 154±2mmHg (SHAM, n=29). Similar reductions in MAP were seen at follow up (-3.5±2.0 vs. -3.2±1.8, P=0.92). Baseline CFR was 2.9±0.1 (RDN) and 2.4±0.1 (SHAM), with no significant change at follow-up (0.2±0.2 vs. -0.1±0.2, P=0.57). C-Rmin was 1.9±0.3 (RDN) and 2.7±0.6 (SHAM) (mmHgmin/ml pr. 100g) and did not change significantly (0.3±0.5 vs. -0.4±0.8, P=0.48). F-Rmin was 3.6±0.2 (RDN) and 3.6±0.3 (SHAM) (mmHgmin/ml pr. 100ml tissue) and unchanged at follow-up (4.2±0.4 vs. 3.8±0.2, P=0.17). Left ventricular mass index was unchanged following RDN (-4±7 (RDN) vs. 3±5 (SHAM) (g/m2) P=0.38). CONCLUSION: The current study does not support positive effects of RDN on microvascular impairment in TRH.

Final five-year outcomes after implantation of biodegradable polymer-coated biolimus-eluting stents versus durable polymer-coated sirolimus-eluting stents.

AIMS: Our aim was to report the long-term safety and efficacy of the biodegradable polymer-coated biolimus- eluting Nobori stent compared to the durable polymer-coated sirolimus-eluting CYPHER stent. METHODS AND RESULTS: SORT OUT V randomised 2,468 patients 1:1 to the Nobori (n=1,229) versus the CYPHER stent (n=1,239). Clinically driven event detection based on Danish registries was used. The primary endpoint was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularisation). Individual components of the primary endpoint comprise the secondary endpoints. At five-year follow-up, the composite endpoint rate was found to be similar in patients treated with the two study stents (Nobori 182/1,229 [14.8%] vs. CYPHER 197/1,239 [15.8%]; odds ratio [OR] 0.93, 95% CI: 0.75-1.16; p=0.53). The rates of definite stent thrombosis were also found to be similar in patients treated with the two study stents (Nobori 23/1,229 [1.9%] vs. CYPHER 18/1,239 [1.5%]; OR 1.31, 95% CI: 0.70-2.47; p=0.40), as were the other secondary endpoints. CONCLUSIONS: At five-year follow-up, the Nobori stent with a biodegradable polymer coating provided a similar safety and efficacy profile when compared to the durable polymer first-generation CYPHER stent.

Patients With Diabetes Without Significant Angiographic Coronary Artery Disease Have the Same Risk of Myocardial Infarction as Patients Without Diabetes in a Real-World Population Receiving Appropriate Prophylactic Treatment.

OBJECTIVE: The risk of myocardial infarction (MI) in patients with diabetes is greater than for patients without diabetes. Consequently, prophylactic treatment is recommended for patients with diabetes and risk factors for ischemic heart disease. We aimed to estimate the risk of adverse cardiac events in patients with and without diabetes with and without coronary artery disease (CAD) after coronary angiography (CAG). RESEARCH DESIGN AND METHODS: A population-based cohort of patients registered in the Western Denmark Heart Registry who underwent CAG between 1 January 2003 and 31 December 2012 was stratified according to the presence or absence of obstructive CAD and diabetes. End points were death, cardiac death, and MI. Unadjusted and adjusted rate ratios (RRs) were calculated by using patients without diabetes and without CAD as the reference group. RESULTS: We included 93,866 patients of whom 12,544 (13.4%) had diabetes at the time of CAG. Median follow-up was 4.1 years. Patients with and without diabetes without obstructive CAD had the same adjusted risk of death (RR 1.03 [95% CI 0.92-1.15]), cardiac death (RR 1.21 [95% CI 0.90-1.64]), and MI (RR 0.88 [95% CI 0.65-1.17]). Patients with diabetes without CAD were more often treated with statins (75.3% vs. 46.0%) and aspirin (65.7% vs. 52.7%) than patients without diabetes and CAD. CONCLUSIONS: In a real-world population, patients with diabetes with high rates of statin and aspirin treatment had the same risk of cardiovascular events as patients without diabetes in the absence of angiographically significant CAD.

Effect of Ischemic Postconditioning During Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial.

Importance: Ischemic postconditioning of the heart during primary percutaneous coronary intervention (PCI) induced by repetitive interruptions of blood flow to the ischemic myocardial region immediately after reopening of the infarct-related artery may limit myocardial damage. Objective: To determine whether ischemic postconditioning can improve the clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, And Participants: In this multicenter, randomized clinical trial, patients with onset of symptoms within 12 hours, STEMI, and thrombolysis in myocardial infarction (TIMI) grade 0-1 flow in the infarct-related artery at arrival were randomized to conventional PCI or postconditioning. Inclusion began on March 21, 2011, through February 2, 2014, and follow-up was completed on February 2, 2016. Analysis was based on intention to treat. Interventions: Patients were randomly allocated 1:1 to conventional primary PCI, including stent implantation, or postconditioning performed as 4 repeated 30-second balloon occlusions followed by 30 seconds of reperfusion immediately after opening of the infarct-related artery and before stent implantation. Main Outcome and Measures: A combination of all-cause death and hospitalization for heart failure. Results: During the inclusion period, 1234 patients (975 men [79.0%] and 259 women [21.0%]; mean [SD] age, 62 [11] years) underwent randomization in the trial. Median follow-up was 38 months (interquartile range, 24-58 months). The primary outcome occurred in 69 patients (11.2%) who underwent conventional primary PCI and in 65 (10.5%) who underwent postconditioning (hazard ratio, 0.93; 95% CI, 0.66-1.30; P = .66). The hazard ratios were 0.75 (95% CI, 0.49-1.14; P = .18) for all-cause death and 0.99 (95% CI, 0.60-1.64; P = .96) for heart failure. Conclusions and Relevance: Routine ischemic postconditioning during primary PCI failed to reduce the composite outcome of death from any cause and hospitalization for heart failure in patients with STEMI and TIMI grade 0-1 flow at arrival. Trial Registration: clinicaltrials.gov Identifier: NCT01435408.

Editor's Choice-Acute versus subacute angiography in patients with non-ST-elevation myocardial infarction - the NONSTEMI trial phase I.

BACKGROUND: The 2015 European Society of Cardiology non-ST-elevation myocardial infarction (NSTEMI) guidelines recommend angiography within 24 h in high-risk patients with NSTEMI. An organized STEMI-like approach with pre-hospital or immediate in-hospital triage for acute coronary angiography (CAG) may be of therapeutic benefit but it remains unknown whether the patients can be properly diagnosed in the pre-hospital setting. We aim to evaluate whether it is feasible to diagnose patients with NSTEMI in the pre-hospital phase or immediately upon admission. METHODS AND RESULTS: We randomized 250 patients to either acute or subacute CAG (i.e. <72 h of admission). Pre-hospital electrocardiogram acquisition and point-of-care troponin-T measurement ensured that 148 (59%) patients were identified already in the ambulance, whereas the remaining 102 (41%) patients were identified immediately after hospital admission. An acute coronary syndrome was verified in 215 (86%) and NSTEMI in 159 (64%) patients. The CAG rate was significantly higher in the acute CAG group (98% vs. 87%, p<0.001). A culprit lesion was identified in 74% and 64% of the patients underwent coronary revascularization: acute CAG group: 53% percutaneous coronary intervention, 5% hybrid, 7% coronary artery bypass grafting; conventional treatment: 48% percutaneous coronary intervention, 2% hybrid, 14% coronary artery bypass grafting, p=0.32. In patients randomized to acute CAG, time from randomization to CAG was 1.1 h; in patients randomized to subacute CAG it was two days. Time from randomization to initial revascularization was 1.3 h versus 2.4 days, and the median hospital stay was 4.0 days versus 4.5 days. Among patients randomized to subacute CAG, 17% crossed over to acute CAG and 5% developed STEMI before catheterization. CONCLUSION: Diagnosing NSTEMI patients in the pre-hospital phase or immediately upon hospital admission is feasible. Acute CAG may impact the mode of revascularization and is associated with earlier revascularization and shorter hospital stay. The clinical benefit of acute CAG in NSTEMI patients remains to be clarified.

Quality indicators for acute myocardial infarction: A position paper of the Acute Cardiovascular Care Association.

Evaluation of quality of care is an integral part of modern healthcare, and has become an indispensable tool for health authorities, the public, the press and patients. However, measuring quality of care is difficult, because it is a multifactorial and multidimensional concept that cannot be estimated solely on the basis of patients' clinical outcomes. Thus, measuring the process of care through quality indicators (QIs) has become a widely used practice in this context. Other professional societies have published QIs for the evaluation of quality of care in the context of acute myocardial infarction (AMI), but no such indicators exist in Europe. In this context, the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) has reflected on the measurement of quality of care in the context of AMI (ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI)) and created a set of QIs, with a view to developing programmes to improve quality of care for the management of AMI across Europe. We present here the list of QIs defined by the ACCA, with explanations of the methodology used, scientific justification and reasons for the choice for each measure.

Risk Associated With Surgery Within 12 Months After Coronary Drug-Eluting Stent Implantation.

BACKGROUND: Guidelines recommend postponing surgery for at least 6 months after treatment with a drug-eluting stent by percutaneous coronary intervention (DES-PCI). OBJECTIVES: The goal of this study was to evaluate the surgical risk associated with DES-PCI compared with that in nonstented patients without ischemic heart disease (IHD). METHODS: Between 2005 and 2012, a total of 22,590 patients underwent DES-PCI in western Denmark. By record-linking the Western Denmark Heart Registry and the Danish National Patient Register, we evaluated 4,303 DES-PCI-treated patients with a surgical procedure and compared them with a control group of patients without previous IHD undergoing similar surgical procedures (n = 20,232). Events of interest were myocardial infarction (MI), cardiac death, and all-cause mortality within 30 days after surgery. RESULTS: Surgery in DES-PCI-treated patients was associated with an increased risk of MI (1.6% vs. 0.2%; odds ratio [OR]: 4.82; 95% confidence interval [CI]: 3.25 to 7.16) and cardiac death (1.0% vs. 0.2%; OR: 5.87; 95% CI: 3.60 to 9.58) but not all-cause mortality (3.1% vs. 2.7%; OR: 1.12; 95% CI: 0.91 to 1.38). When stratified for time from PCI to surgery, only surgery within the first month was associated with a significant increased risk of events. CONCLUSIONS: Patients requiring surgery within 12 months after DES-PCI had an increased risk of MI and cardiac death compared with patients without IHD. The increased risk was only present within the first month after DES-PCI, suggesting that surgery might be undertaken earlier than currently recommended.

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on "New frontiers in cardiovascular research".

In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients' cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia-reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients' outcome.