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Obstructive sleep apnea (OSA) increases the risk of cardiovascular disease (CVD) in both morbidity and mortality. We used the risk chart of Systemic Coronary Risk Evaluation (SCORE) from European Society of Cardiology (ESC) to determine the 10-year risk of cardiovascular death, and adherence to cardiovascular risk factor management in Danish patients investigated for obstructive sleep apnea. In a prospective cohort study, 303 patients with mild, moderate and severe OSA were investigated for cardiovascular risk factors before initiating CPAP therapy. Primary outcome was estimates of 10-year risk of cardiovascular death assessed from the ESC risk chart SCORE based on sex, age, smoking status, systolic blood pressure and s-total cholesterol. Furthermore we analyzed treatment indication with statins in patients with mild (apnea-hypopnea index, AHI <15), moderate (AHI 15–29.9) and severe OSA (AHI ≥30). Patients with mild OSA predominately had low or moderate 10-year risk of CVD (low risk 55.4%, moderate risk 30.8%) while patients with moderate and severe OSA were more likely to have high or very high risk of 10-year CVD (p = 0.001). The large majority of included OSA patients had dyslipidemia, 235 (77.6%) and of those, only 27.4% were treated with cholesterol lowering drugs while additional 27.7% were eligible for oral statin supplement as risk-estimated by the ESC SCORE. In multiple regression analysis among statin naive patients, AHI was positively associated with statin eligibility when adjusted for age and sex. Patients with moderate and severe OSA had an elevated 10-year risk of fatal CVD and were undertreated with CVD risk lowering agents such as statins. • Obstructive sleep apnea (OSA) increases the risk of cardiovascular disease (CVD) in both morbidity and mortality. • The 10-year risk of fatal CVD increase along with cardiovascular risk factors with severity of OSA. • More than 1 in 4 at risk and statin naïve OSA patients were eligible for cholesterol-lowering therapy yet untreated. • This study warrant greater attention to CVD and risk factor management in OSA patients. [ABSTRACT FROM AUTHOR]

Objective: Patients with silent and undiagnosed atrial fibrillation (AF) have increased risk of ischemic stroke. Patients with obstructive sleep apnea (OSA) have an increased risk of both AF and ischemic stroke. Our aim was to investigate the prevalence of silent AF and associated risk factors in patients investigated for OSA or with known OSA.Methods: This prospective observational study was performed in two sites; one outpatient sleep-clinic at Zealand University Hospital and one private Ear-Nose- and Throat clinic. Patients were investigated with a type-3 portable sleep-monitoring device, while heart rhythm was home-monitored for 7 days with an event-triggered loop recorder. Patients were stratified in groups of mild, moderate and severe OSA based on Apnea-Hypopnea-Index (AHI).Results: In a cohort of 303 patients, 238 (78.5%) were diagnosed with moderate/or severe OSA and 65 (21.5%) with no/mild OSA who constituted the control group. In 238 patients with moderate and severe OSA, AF was detected in 21 patients (8.8%) vs. 1 patient (1.5%,[p=0.045]) with mild OSA. Candidates for anticoagulation therapy were referred for further cardiovascular treatment. The majority of patients had known hypertension (n = 200,66%) and dyslipidemia (n = 235,[77.6%]) In patients with moderate/or severe OSA (AHI≥15), hypertension was more dysregulated (p=0.005) and more patients suffered from unknown prediabetes (n = 36, 3.1% vs. 14.3%[p<0.001]).Conclusion: Undiagnosed AF and undertreated cardiovascular modifiable risk factors are common in a cohort of patients with OSA. With this study we propose that long-period home-monitoring in these patients is useful for identifying candidates for preventive anticoagulation, cardiovascular treatment and possibly prevent future ischemic stroke. [ABSTRACT FROM AUTHOR]

Background Primary percutaneous coronary intervention (pPCI) is recommended in patients presenting with ST-elevation myocardial infarction (STEMI) within <12 h of symptom onset. However, patients-reported symptom duration is not always reliable. Cardiac specific troponin T (cTnT) and the endogenous stress marker copeptin have different temporal release patterns for myocardial infarction MI. We hypothesized that copeptin/troponin-ratio is associated to the duration of coronary occlusion and therefore inversely proportional to myocardial salvage. Method Patients older than 18 years with first time STEMI referred to pPCI were eligible. cTnT and copeptin values were measured at admission. A cardiac magnetic resonance scanning (CMR) was done during the index admission for assessment of area at risk (AAR), and later 3 months to assess final infarct size (FIS). Myocardial salvage index (MSI) was calculated based on these measurements. Results A total of 468 patients were included. The median time from patient-reported onset of symptoms to pPCI was 192 min (IQR 150 min - 290 min). At presentation 416 (89%) patients had hs-cTnT values above the 99th percentile, median hs-cTnT was 53 ng/l (IQR 24 ng/l-146 ng/l) and 318 (68%) patients had copeptin values above the 99th percentile (18.9 pmol/l), median copeptin was 50 pmol/l (IQR 14 pmol/l-131 pmol/l). Symptom duration showed a weak but significant association with AAR (R 2  = 0.02, p  = .04), FIS (R 2  = 0.03, p  < .01) and MSI (R 2  = 0.04, p < .01). Copeptin/troponin-ratio was significantly associated with symptom duration (R 2  = 0.19, p < .01), but not AAR (R 2  = 0.02, p  = .19), FIS (R 2  = 0.02, p  = .12), or MSI (R 2  = 0.01, p  = .25). Conclusion Copeptin/troponin-ratio is associated with patient-reported symptom duration, but there was no association with area at risk, final infarct size or myocardial salvage index. [ABSTRACT FROM AUTHOR]

Objectives: Iron deficiency (ID) might augment chronic pulmonary hypertension in chronic obstructive pulmonary disease (COPD). This observational study investigates the association between ID and systolic pulmonary artery pressure estimated by echocardiography in non-anaemic COPD outpatients.Methods: Non-anaemic COPD patients (GOLD II-IV) with no history of cardiovascular disease were recruited from outpatient clinics. Iron deficiency was defined as ferritin<100μg/L. Pulmonary artery pressure was estimated from the tricuspid regurgitation maximum velocity (TR Vmax). Tricuspid regurgitation Vmax indicative of pulmonary hypertension was considered present for values ≥ 2.9 m/s.Results: In a total of 75 included patients, 31 (41%) had ID. These patients had a significantly higher TR Vmax (3.02 vs. 2.77 m/s, p=0.01) and lower diffusion capacity of carbon monoxide (40% vs. 50% of predicted, p<0.01), though similar in age, sex, pack years, FEV1 and high-sensitive CRP (p>0.05). Ferritin inversely correlated with TR Vmax in ID patients (-0.37 (p=0.04)). The prevalence of TR Vmax ≥ 2.9 m/s was twice as high in patients with ID (58% vs. 29%) and odds ratio of pulmonary hypertension in ID (compared to no ID) was 3.3 (95% CI 1.3-8.6, p=0.015).Conclusion: Iron deficiency in non-anaemic COPD patients was associated with a modest increase in systolic pulmonary artery pressure and limitation of diffusion capacity. [ABSTRACT FROM AUTHOR]

An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether HbA1c levels are associated with high platelet reactivity (HPR) in patients loaded with clopidogrel and aspirin, thereby constituting an argument for intensified antiplatelet therapy in patients with poor glycemic control. In the prospective, multicenter Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c <6.5% (n = 551, 48.12%), 6.5% to 8.5% (n = 423, 36.9%), and >8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208 and aspirin reaction units >550, respectively. HPR on clopidogrel was frequent (48.3%), whereas HPR on aspirin was not (3.9%). Patients with HbA1c >8.5% were younger, more likely non-Caucasian, had a greater body mass index, and more insulin-treated diabetes and acute coronary syndromes. Proportions of PRU >208 (42.5%, 50.2%, and 62.3%, p <0.001) and rates of definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models that included PRU, high HbA1c levels (>8.5) remained associated with ST (hazard ratio 3.92, 95% CI 1.29 to 12.66, p = 0.02) and cardiac death (hazard ratio 4.24, 95% CI 1.41 to 12.70) but not bleeding at 2-year follow-up. There was no association between aspirin reaction units >550 and HbA1c levels. In conclusion, in this large-scale study, HbA1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control, which predicted ST and cardiac death after PCI regardless of PRU levels, warranting efforts to improve glycemic control after DES implantation in patients with diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: The European Society of Cardiology (ESC) guideline on non-ST-elevation acute coronary syndrome (N-STE ACS) proposed a new ACS rule-out protocol.Objectives: To evaluate this new tool, which uses diagnostic levels of high-sensitivity troponin T (hs-TnT; > 14 ng/L) in a slightly modified version and compare this to a recently proposed approach using undetectable levels of hs-TnT to rule out patients.Methods: There were 534 consecutive patients with suspected ACS included. Protocol 1: symptom duration, hs-TnT at 0 and 6-9 h, Global Registry of Acute Coronary Events (GRACE) score, and symptom status at 6-9 h. Protocol 2: a single blood sample of hs-TnT. The primary endpoint was a discharge diagnosis of ACS by blinded adjudication. Secondary endpoints were ACS re-admission < 30 days and 1-year mortality.Results: Protocol 1 classified 434/534 (81%) patients, with 27.9% being ruled out. All myocardial infarctions were correctly ruled in, but 15 cases of unstable angina were missed, resulting in a sensitivity and negative predictive value of 87.3% (79.6-92.5%) and 87.6% (80.4-92.9%), respectively. Protocol 2 ruled out 17.5% of the population, yielding a sensitivity and negative predictive value of 94.1% (88.2-97.6%) and 90.8% (81.9-96.2%), respectively. Both protocols correctly ruled in 2/3 patients with ACS re-admission < 30 days and 55/56 1-year fatalities.Conclusion: The present study confirms the diagnostic value of a modified version of the ESC rule-out protocol (Protocol 1) in N-STE ACS patients, but also suggests that a simpler protocol using undetectable levels of hs-TnT (Protocol 2) could provide a similar or even superior sensitivity. [ABSTRACT FROM AUTHOR]

Adequate health care is increasingly dependent on prehospital systems and cardiovascular (CV) disease remains the most common cause for hospital admission. However the prevalence of CV dispatches of emergency medical services (EMS) is not well reported and survival data described in clinical trials and registries are subject to selection biases. We aimed to describe the prevalence and prognosis of acute CV disease and the effect of invasive treatment, in an unselected and consecutive prehospital cohort of 3,410 patients calling the national emergency telephone number from 2005 to 2008 with follow-up in 2013. Individual-level data from national registries were linked to the dedicated EMS database of primary ambulance dispatches supported by physician-manned emergency units. Outcome data were obtained from the Central Population Registry, the National Patient Registry, and the National Registry of Causes of Death. In patients calling the national emergency telephone number, a CV related ambulance alarm code was given in 2,541 patients of 3,410 patients (74.5%) resulting in 2,056 of 3,410 primary CV discharge diagnoses (60.3%) with a 30-day and 5-year all-cause mortality of 24.5% and 46.4%, respectively. Stroke, acute heart failure, and ST-segment elevation myocardial infarction (STEMI) carried a 25- to 50-fold adjusted mortality hazard during the first 4 days. In patients with suspected STEMI, 90.5% had an acute angiography performed. Nontransferred, nonreperfused patients with STEMI (9.1%) carried 80% short-term mortality. Noninvasive management of non-ST-segment elevation myocardial infarction was common (37.9%) and associated with an increased adjusted long-term mortality hazard (hazard ratio 4.17 [2.51 to 8.08], p <0.001). Survival in 447 out-of-hospital cardiac arrest patients (13.1%) was 11.6% at 30 days. In conclusion, patients with a CV ambulance alarm call code and a final CV discharge diagnosis constitute most patients handled by EMS with an extremely elevated short-term mortality hazard and a poor long-term prognosis. Although co-morbidities and frailty may influence triage, this study emphasizes the need for an efficient prehospital phase with focus on CV disease and proper triage of patients suitable for invasive evaluation if the outcomes of acute heart disease are to be improved further in the current international context of hospitals merging into highly specialized entities resulting in longer patient transfers. [ABSTRACT FROM AUTHOR]

Objectives: We hypothesized that prehopsital ECG scores can identify ST-segment elevation myocardial infarction (STEMI) patients in whom time delay is particularly important for myocardial salvage. Methods: We evaluated the Anderson-Wilkins (AW) score (which designates the acuteness of ischemia) and grade 3 ischemia (GI3) (which identifies severe ischemia) in the prehospital ECG and compared them to the myocardial salvage index (MSI) assessed by cardiac magnetic resonance. Results: In 150 patients, system delay (alarm to balloon inflation) (β = -0.304, p < 0.001) and AW score (β = 0.364, p < 0.001) correlated with MSI. AW scores ≥3 (p < 0.001) and GI3 (p = 0.002) predicted the MSI. We formed 4 subgroups combining AW scores (<3 or ≥3) and grades of ischemia (

Abstract: Background: Lectin complement pathway (LP) activation is an important mechanism in myocardial ischemia reperfusion injury (IRI). LP is activated via the recognition molecules mannose-binding lectin (MBL), ficolins-2 and-3 and is regulated by MBL/Ficolin-associated Protein-1 (MAP-1). Also, C-reactive protein (CRP) and ficolin-2 interact in vitro, but the role of the ficolins in IRI is unknown. Methods and results: In 55 patients with ST segment elevation myocardial infarction, we investigated the association of LP components and CRP in plasma samples with left ventricular (LV) end systolic and diastolic volumes (ESV and EDV) and infarct size, assessed by cardiac magnetic resonance early at 1–3 days after primary percutaneous coronary intervention and at 6 months follow-up. Opposed to MBL, ficolin-3 and MAP-1, ficolin-2 levels were low at baseline. At baseline, ficolin-2>median was associated with ESV and EDV increases by 7.83ml/m2 (p =0.004) and 14.04ml/m2 (p <0.001). MBL and MAP-1 were not associated with LV dilatation, yet ficolin-2 and MBL worked synergistically and the combination of their levels>median was associated with ESV (11.21ml/m2; p =0.017) and EDV increases (14.72ml/m2; p =0.006). MAP-1median had the greatest LV dilatation (17.61ml/m2). The ficolin-2×CRP interaction variable was positively associated with infarct size and inversely associated with EDV change over 6 months (p =0.006). There was no interaction between CRP and the other LP molecules. Conclusion: The LP initiator molecule ficolin-2 and combinations of ficolin-2, MBL and MAP-1 are associated with LV dilatation after myocardial infarction. Interaction of ficolin-2 and CRP was associated with infarct size and LV remodeling, indicating a potential role for LP and LP-pentraxin cross-activation in IRI and LV remodeling. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Objective. Pregnancy-associated plasma protein A (PAPP-A) is expressed in eroded and ruptured atheromatous plaques, and circulating levels are elevated in acute coronary syndromes (ACS). Our objective was to investigate release patterns of PAPP-A in ACS and whether they differ among different types of ACS. Methods. In 40 patients, PAPP-A concentrations were measured in serially collected samples assessed by a novel ELISA technique. The patients were grouped according to type of ACS. Results. Release patterns for ST elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI) showed a single substantial PAPP-A increase shortly after pPCI, followed by an abrupt return to normal levels without secondary peaks. STEMI, high-risk and low-risk non-ST elevation myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients without pPCI showed highly variable patterns with primary peaks followed by secondary PAPP-A increases. All patients with elevated PAPP-A levels reached the upper reference level within 24 h. There was a significant difference in median peak levels between STEMI (23.2 mIU/L) and low-risk ACS patients (6.35 mIU/L) (p = 0.004) and between high-risk (median = 15.3 mIU/L) and low-risk ACS patients (p = 0.01). Among high-risk ACS patients, NSTEMI patients had significantly higher peak levels than UAP patients (p = 0.003). Conclusion. PAPP-A serum levels increase above normal values within 24 h after onset of symptoms in ACS. There are significant differences in PAPP-A peak levels and release patterns across the spectrum of ACS patients. [ABSTRACT FROM AUTHOR]

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

To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47–36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07–50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27–47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83–328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization. • Irreversible damage to the myocardium after STEMI can be predicted in 47% of the patients. • ICD implantation can be considered in these patients with irreversible damage to the myocardium. • Cardiac MRI during admission for STEMI can help directing the future treatment in selected patients. • 77% of STEMI patients with LVEF <35% will experience increase in their LVEF to >35% within three months. [ABSTRACT FROM AUTHOR]

Background Terminal QRS distortion on the electrocardiogram (ECG) is a sign of severe ischemia in patients with STEMI and can be quantified by the Sclarovsky-Birnbaum Severity of Ischemia. Due to score complexity, it has not been applied in clinical practice. Automatic scoring of digitally recorded ECGs could facilitate clinical application. We aimed to develop an automatic algorithm for the severity of ischemia. Methods Development set: 50 STEMI ECGs were manually (Manual-score) and automatically (Auto-score) scored by our designed algorithm. The agreement between Manual- and Auto-score was assessed by kappa statistics. Test set: ECGs from 199 STEMI patients were assigned a severity grade (severe or non-severe ischemia) by the Auto-score. Infarct size estimated by median peak Troponin T (TnT) and Creatinine Kinase Myocardial Band (CKMB) was tested between the groups. Results The agreement between Manual- and Auto-score was 0.83 ((95% CI 0.55–1.00), p < 0.0001), sensitivity 75% and specificity 100%, PPV 100% and NPV 94.6%. In the test set 152 (76%) patients were male, mean age 61 ± 12 years. The Auto-score designated severe ischemia in 42 (21%) and non-severe ischemia in 157 (79%) patients. Patients with ECG signs of severe vs. non-severe ischemia had significantly higher levels of biomarkers of infarct size. In multiple linear regression, ECG sign of severe ischemia was an independent predictor for higher TnT and CKMB levels. Conclusion The automatic ECG algorithm for severity of ischemia in STEMI performs adequately for clinical use. Severe ischemia obtained by the Auto-score was associated with biomarker estimated larger infarct size. [ABSTRACT FROM AUTHOR]

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

Patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) are at elevated risk for bleeding and thromboembolic ischemic events. Currently, guidelines on antithrombotic treatment for these patients are based on weak consensus. We describe patterns and determinants of antithrombotic prescriptions in this population. The Antithrombotic Strategy Variability in Atrial Fibrillation and Obstructive Coronary Disease Revascularized with PCI Registry was an international observational study of 859 consecutive patients with AF who underwent PCI from 2009 to 2011. Patients were stratified by treatment at discharge with either dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) or triple therapy (TT; warfarin plus DAPT). Bleeding and thromboembolism risks were assessed by the HAS-BLED and CHADS2 scores, respectively, and predictors of TT prescription at discharge were identified. Major adverse cardiovascular events and clinically relevant bleeding (Bleeding Academic Research Consortium score ≥2) at 1-year follow-up were compared across antithrombotic regimens. Compared with patients on DAPT (n = 488; 57%), those given TT (n = 371; 43%) were older, with higher CHADS2 scores, lower left ventricular ejection fraction, and more often had permanent AF, single-vessel coronary artery disease, and bare-metal stents. In multivariate analysis, increasing thromboembolic risk (CHADS2) was associated with a higher rate of TT prescription at discharge (intermediate vs low CHADS2: odds ratio 2.2, 95% confidence interval [CI] 2.0 to 3.3, p <0.01; high vs low CHADS2: odds ratio 1.6, 95% CI 2.6 to 4.3, p <0.01 for TT). However, there was no significant association between bleeding risk and TT prescription in the overall cohort or within each CHADS2 risk stratum. The rates of major adverse cardiovascular events were similar for patients discharged on TT or DAPT (20% vs 17%, adjusted hazard ratio 0.8, 95% CI 0.5 to 1.1, p = 0.19), whereas the rate of Bleeding Academic Research Consortium ≥2 bleeding was higher in patients discharged on TT (11.5% vs 6.4%, adjusted hazard ratio 1.8, 95% CI 1.1 to 2.9, p = 0.02). In conclusion, the choice of the intensity of antithrombotic therapy correlated more closely with the risk of ischemic rather than bleeding events in this cohort of patients with AF who underwent PCI. [ABSTRACT FROM AUTHOR]

BACKGROUND Although recent studies suggest that measuring coronary artery calcification (CAC) may be superior to indirect atherosclerotic markers in predicting cardiac risk, there are limited data evaluating imaging-based biomarkers that directly quantify atherosclerosis in different vascular beds performed in a single cohort. OBJECTIVES The Biolmage Study (A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population) sought to identify imaging biomarkers that predict near-term (3-year) atherothrombotic events. METHODS The Biolmage Study enrolled 5,808 asymptomatic U.S. adults (mean age: 69 years, 56.5% female) in a prospective cohort evaluating the role of vascular imaging on cardiovascular risk prediction. All patients were evaluated by CAC and novel 3-dimensional carotid ultrasound. Plaque areas from both carotid arteries were summed as the carotid plaque burden (cPB). The primary endpoint was the composite of major adverse cardiac events (MACE) (cardiovascular death, myocardial infarction, and ischemic stroke). A broader secondary MACE endpoint also included all-cause death, unstable angina, and coronary revascularization. RESULTS Over a median follow-up of 2.7 years, MACE occurred in 216 patients (4.2%), of which 82 (1.5%) were primary events. After adjustment for risk factors, and compared with individuals without any cPB, hazard ratios for MACE were 0.78 (95% confidence interval [Cl]: 0.31 to 1.91), 1.45 (95% Cl: 0.67 to 3.14), and 2.36 (95% Cl: 1.13 to 4.92) with increasing cPB tertile, with similar results for CAC. Net reclassification significantly improved with either cPB (0.23) or CAC (0.25). MACE rates increased simultaneously with higher levels of both cPB and CAC. CONCLUSIONS Detection of subclinical carotid or coronary atherosclerosis improves risk predictions and reclassification compared with conventional risk factors, with comparable results for either modality. Cost-effective analyses are warranted to define the optimal roles of these complementary techniques. (Biolmage Study: A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population; NCT00738725) (J Am Coll Cardiol 2015;65:1065-74) [ABSTRACT FROM AUTHOR]

Background: Although recent studies suggest that measuring coronary artery calcification (CAC) may be superior to indirect atherosclerotic markers in predicting cardiac risk, there are limited data evaluating imaging-based biomarkers that directly quantify atherosclerosis in different vascular beds performed in a single cohort.Objectives: The BioImage Study (A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population) sought to identify imaging biomarkers that predict near-term (3-year) atherothrombotic events.Methods: The BioImage Study enrolled 5,808 asymptomatic U.S. adults (mean age: 69 years, 56.5% female) in a prospective cohort evaluating the role of vascular imaging on cardiovascular risk prediction. All patients were evaluated by CAC and novel 3-dimensional carotid ultrasound. Plaque areas from both carotid arteries were summed as the carotid plaque burden (cPB). The primary endpoint was the composite of major adverse cardiac events (MACE) (cardiovascular death, myocardial infarction, and ischemic stroke). A broader secondary MACE endpoint also included all-cause death, unstable angina, and coronary revascularization.Results: Over a median follow-up of 2.7 years, MACE occurred in 216 patients (4.2%), of which 82 (1.5%) were primary events. After adjustment for risk factors, and compared with individuals without any cPB, hazard ratios for MACE were 0.78 (95% confidence interval [CI]: 0.31 to 1.91), 1.45 (95% CI: 0.67 to 3.14), and 2.36 (95% CI: 1.13 to 4.92) with increasing cPB tertile, with similar results for CAC. Net reclassification significantly improved with either cPB (0.23) or CAC (0.25). MACE rates increased simultaneously with higher levels of both cPB and CAC.Conclusions: Detection of subclinical carotid or coronary atherosclerosis improves risk predictions and reclassification compared with conventional risk factors, with comparable results for either modality. Cost-effective analyses are warranted to define the optimal roles of these complementary techniques. (BioImage Study: A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population; NCT00738725). [ABSTRACT FROM AUTHOR]

Background: The prospective, randomized FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial found coronary artery bypass graft surgery (CABG) was associated with better clinical outcomes than percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease, managed with or without insulin.Objectives: In this subgroup analysis of the FREEDOM trial, we examined the association of long-term clinical outcomes after revascularization in patients with insulin-treated diabetes mellitus (ITDM) compared with patients not treated with insulin.Methods: A total of 1,850 FREEDOM subjects had an index revascularization procedure performed: 956 underwent PCI with drug-eluting stents (DES), and 894 underwent CABG. A total of 602 patients (32.5%) had ITDM (PCI/DES n = 325, 34%; CABG n = 277, 31%). Subjects were classified according to ITDM versus non-ITDM, with comparison of PCI/DES versus CABG for each group. Interaction analyses were performed for treatment by diabetes mellitus (DM) status alone and for treatment by DM status by coronary lesion complexity. Analyses were performed for the primary outcome composite of death/stroke/myocardial infarction (MI) using all available follow-up data.Results: The overall 5-year event rate of death/stroke/MI was significantly higher in ITDM versus non-ITDM patients (28.7% vs. 19.5%, p < 0.001), which persisted even after adjustment for multiple baseline factors, angiographic complexity, and revascularization treatment group (death/stroke/MI hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.06 to 1.73, p = 0.014). With respect to the primary composite endpoint, CABG was superior to PCI/DES in both DM types and the magnitude of treatment effect was similar (interaction p = 0.40) for ITDM (PCI vs.Cabg Hr: 1.21; 95% CI: 0.87 to 1.69) and non-ITDM patients (PCI vs.Cabg Hr: 1.46; 95% CI 1.10 to 1.94), even after adjusting for the angiographic SYNTAX score level. Based on 5-year event rates, the number needed to treat with CABG versus PCI to prevent 1 event is 12.7 in ITDM and 13.2 in non-ITDM.Conclusions: In patients with diabetes and multivessel coronary artery disease, the rate of major adverse cardiovascular events (death, MI, or stroke) is higher in patients treated with insulin than in those not treated with insulin. Furthermore, we did not detect a significant difference in the magnitude of PCI versus CABG treatment effect for patients treated with insulin and those not treated with insulin. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450). [ABSTRACT FROM AUTHOR]

Background The prospective, randomized FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial found coronary artery bypass graft surgery (CABG) was associated with better clinical outcomes than percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease, managed with or without insulin. Objectives In this subgroup analysis of the FREEDOM trial, we examined the association of long-term clinical outcomes after revascularization in patients with insulin-treated diabetes mellitus (ITDM) compared with patients not treated with insulin. Methods A total of 1,850 FREEDOM subjects had an index revascularization procedure performed: 956 underwent PCI with drug-eluting stents (DES), and 894 underwent CABG. A total of 602 patients (32.5%) had ITDM (PCI/DES n = 325, 34%; CABG n = 277, 31%). Subjects were classified according to ITDM versus non-ITDM, with comparison of PCI/DES versus CABG for each group. Interaction analyses were performed for treatment by diabetes mellitus (DM) status alone and for treatment by DM status by coronary lesion complexity. Analyses were performed for the primary outcome composite of death/stroke/myocardial infarction (MI) using all available follow-up data. Results The overall 5-year event rate of death/stroke/MI was significantly higher in ITDM versus non-ITDM patients (28.7% vs. 19.5%, p < 0.001), which persisted even after adjustment for multiple baseline factors, angiographic complexity, and revascularization treatment group (death/stroke/MI hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.06 to 1.73, p = 0.014). With respect to the primary composite endpoint, CABG was superior to PCI/DES in both DM types and the magnitude of treatment effect was similar (interaction p = 0.40) for ITDM (PCI vs. CABG HR: 1.21; 95% CI: 0.87 to 1.69) and non-ITDM patients (PCI vs. CABG HR: 1.46; 95% CI 1.10 to 1.94), even after adjusting for the angiographic SYNTAX score level. Based on 5-year event rates, the number needed to treat with CABG versus PCI to prevent 1 event is 12.7 in ITDM and 13.2 in non-ITDM. Conclusions In patients with diabetes and multivessel coronary artery disease, the rate of major adverse cardiovascular events (death, MI, or stroke) is higher in patients treated with insulin than in those not treated with insulin. Furthermore, we did not detect a significant difference in the magnitude of PCI versus CABG treatment effect for patients treated with insulin and those not treated with insulin. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450 ). [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To examine if pregnancy-associated plasma protein-A (PAPP-A) in patients with chest pain, could identify patients at risk for death or myocardial infarction. Design and methods: Patients admitted with chest pain and both normal ECG and normal biomarkers were evaluated by serial measurement of PAPP-A. Main outcome measures were mortality and non-fatal myocardial infarction. Results: Median age of patients included (415) was 67years and 43% were women. The risk of death or non-fatal myocardial infarction after 3 months was 15% in the highest quartile of circulating PAPP-A compared with 3% in the lowest quartile (relative risk 3.7, p <0.01). Corresponding numbers after 1 year were 24% and 10% (relative risk 2.4, p =0.01). Conclusion: In patients admitted with chest pain and both normal ECG and normal biomarkers PAPP-A seems to be valuable for predicting patients at high risk of death or non-fatal myocardial infarction. [Copyright &y& Elsevier]

To investigate whether pregnancy-associated plasma protein-A (PAPP-A) is a prognostic marker in patients admitted with high-risk acute coronary syndrome. In patients admitted with high-risk non–ST-segment elevation acute coronary syndrome (NSTE-ACS) and ST-segment elevation myocardial infarction (STEMI), risk stratification is primarily determined by the markers of myocardial necrosis and known demographic risk profiles. However, it has recently been proposed that the presence and extent of vulnerable plaques might influence the prognosis significantly. A marker for the vulnerable plaque could identify patients at high risk who would potentially benefit from intensive treatment and surveillance. Two populations of consecutive patients admitted with high-risk NSTE-ACS (n = 123) and STEMI (n = 314) were evaluated with serial measurements of PAPP-A. The incidence of mortality and nonfatal myocardial infarction was prospectively registered for 2.66 to 3.47 years. In the patients with high-risk NSTE-ACS, PAPP-A was related to the risk of nonfatal myocardial infarction (p = 0.02) and death (p = 0.03). This result was consistent on multivariate analysis of the combination of mortality or nonfatal myocardial infarction (odds ratio 2.65, 95% confidence interval 1.40 to 5.03) but not for mortality alone (p = NS). In patients with STEMI, PAPP-A was related to the risk of death (p = 0.01) but not the composite outcome of myocardial infarction and death. This was also true after adjustment for other univariate predictors of death (odds ratio 2.19, 95% confidence interval 1.16 to 4.16). In conclusion, PAPP-A seems to be valuable in predicting the outcomes of patients admitted with high-risk NSTE-ACS or STEMI. [Copyright &y& Elsevier]

Objective: Patients with silent and undiagnosed paroxysmal atrial fibrillation and flutter (AF) have increased risk of ischemic stroke. Patients with diabetes have a higher risk of both AF and ischemic stroke compared to patients without diabetes. Our aim was to investigate the prevalence of silent AF in patients with diabetes in an outpatient cohort and to identify the possible risk factors associated with AF.Research Design and Methods: This prospective observational study was performed in the outpatient diabetes clinic at a single University Hospital. We included 217 patients with type 1 or type 2 diabetes with at least one additional risk factor from the CHA2DS2VASc Score for Stroke Risk Assessment in Atrial Fibrillation. The primary outcome was prevalence of AF, with a duration of at least 30 s, recorded by a seven-day home-monitor, external loop recorder (ELR) in comparison to a standard resting ECG. Seventeen patients were excluded due to premature removal of the device.Results: In the final cohort of 200 patients the majority were male (58.5%) with a mean age of 66 ± 0.7 years. The mean BMI was 29 ± 6 and patients had a mean diabetes history of 23 ± 14 years with the majority diagnosed with type 2 diabetes (59%). Comorbidity was common with hypertension in 86%, and dyslipidemia in 80%. The total prevalence of silent AF [n = 20 (10%)] or flutter [n = 1 (0.5%)] was 10.5% using the ELR compared to a 0.0% detection-rate in the standard ECG method (p < 0.001). Higher age, male gender, albuminuria, and elevated systolic blood pressure were associated with AF in univariate analyses, but only age [OR 1.14 (95% CI = 1.00-2.04) (p = 0.048)], male gender [OR 4.9 (95% CI = 1.30-18.65) (p = 0.019)] and albuminuria [OR 2.7 (95% CI =1.08-6.98) (p = 0.034) were independently associated with AF. Mean CHA2DS2VASc Score was ≥2 (4.1, SD ± 1.6), and patients with AF were referred to further cardiac evaluation.Conclusion: Undiagnosed, silent AF is common in high-risk cohort with a long history of diabetes followed in a University Hospital outpatient clinic. Non-invasive monitoring with ELR enhances detection of AF and identifies candidates for early anticoagulation treatment with the possible effect of stroke prevention. [ABSTRACT FROM AUTHOR]