Estimates of 10-year risk of cardiovascular death and adherence to cardiovascular risk factor management in Danish patients investigated for obstructive sleep apnea.

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Recurring episodes of bundle branch reentry ventricular tachycardia due to aortitis preceded by SARS-CoV-2 infection: a case report.

BACKGROUND: SARS-CoV-2 may trigger both vasculitis and arrhythmias as part of a multisystem inflammatory syndrome described in children as well as in adults following COVID-19 infection with only minor respiratory symptoms. The syndrome denotes a severe dysfunction of one or more extra-pulmonary organ systems, with symptom onset approximately 2-5 weeks after the COVID-19 infection. In the present case, a seemingly intractable ventricular tachycardia preceded by SARS-CoV2 infection was only managed following the diagnosis and management of aortitis. CASE PRESENTATION: A 69-year-old woman was hospitalized due to syncope, following a mild COVID-19 infection. She presented with paroxysmal atrial fibrillation and intermittent ventricular tachycardia interpreted as a septum-triggered bundle branch reentry ventricular tachycardia, unaffected by amiodaron, lidocaine and adenosine. A CT-scan revealed inflammation of the aortic arch, extending into the aortic root. In the following days, the tachycardia progressed to ventricular storm with intermittent third-degree AV block. A temporary pacemaker was implanted, and radiofrequency ablation was performed to both sides of the ventricular septum after which the ventricular tachycardia was non-inducible. Following supplemental prednisolone treatment, cardiac symptoms and arrythmia subsided, but recurred after tapering. Long-term prednisolone treatment was therefore initiated with no relapse in the following 14 months. CONCLUSION: We present a rare case of aortitis complicated with life-threatening ventricular tachycardia presided by Covid-19 infection without major respiratory symptoms. Given a known normal AV conduction prior to the COVID-19 infection, it seems likely that the ensuing aortitis in turn affected the septal myocardium, enabling the reentry tachycardia. Generally, bundle branch reentry tachycardia is best treated with radiofrequency ablation, but if it is due to aortitis with myocardial affection, long-term anti-inflammatory treatment is mandatory to prevent relapse and assure arrhythmia control. Our case highlights importance to recognize the existence of the multisystem inflammatory syndrome in adults (MIS-A) following COVID-19 infection in patients with alarming cardiovascular symptoms. The case shows that the early use of an CT-scan was crucial for both proper diagnosis and treatment option.

Prevalence of silent atrial fibrillation and cardiovascular disease in patients with obstructive sleep apnea.

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.

Polypill Strategy in Secondary Cardiovascular Prevention.

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).

Ischemia From Nonculprit Stenoses Is Not Associated With Reduced Culprit Infarct Size in Patients with ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: In patients with ST-segment-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention, reperfusion injury accounts for a significant fraction of the final infarct size, which is directly related to patient prognosis. In animal studies, brief periods of ischemia in noninfarct-related (nonculprit) coronary arteries protect the culprit myocardium via remote ischemic preconditioning. Positive fractional flow reserve (FFR) documents functional significant coronary nonculprit stenosis, which may offer remote ischemic preconditioning of the culprit myocardium. The aim of the study was to investigate the association between functional significant, multivessel disease (MVD) and reduced culprit final infarct size or increased myocardial salvage (myocardial salvage index [MSI]) in a large contemporary cohort of STEMI patients. METHODS: Cardiac magnetic resonance was performed in 610 patients with STEMI at day 1 and 3 months after primary percutaneous coronary intervention. Patients were stratified into 3 groups according to FFR measurements in nonculprit stenosis (if any): angiographic single vessel disease (SVD), FFR nonsignificant MVD (functional SVD), or FFR-significant, functional MVD. RESULTS: A total of 431 (71%) patients had SVD, 35 (6%) had functional SVD, and 144 (23%) had functional MVD. There was no difference in final infarct size (mean infarct size [%left ventricular mass] SVD, 9±3%; functional SVD, 9±3%; and functional MVD, 9±3% [P=0.82]) or in MSI between groups (mean MSI [%left] SVD, 66±23%; functional SVD, 68±19%; and functional MVD, 69±19% [P=0.62]). In multivariable analyses, functional MVD was not associated with larger MSI (P=0.56) or smaller infarct size (P=0.55). CONCLUSIONS: Functional MVD in nonculprit myocardium was not associated with reduced culprit final infarct size or increased MSI following STEMI. This is important knowledge for future studies examining a cardioprotective treatment in patients with STEMI, as a possible confounding effect of FFR-significant, functional MVD can be discarded. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).

Silent atrial fibrillation detected by home-monitoring: Cardiovascular disease and stroke prevention in patients with diabetes.

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 ±â€¯0.7 years. The mean BMI was 29 ±â€¯6 and patients had a mean diabetes history of 23 ±â€¯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 ±â€¯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.

Impact of Multiple Myocardial Scars Detected by CMR in Patients Following STEMI.

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

Importance of elevated heart rate in the very early phase of ST-segment elevation myocardial infarction: Results from the DANAMI-3 trial.

BACKGROUND: Elevated heart rate is associated with poor clinical outcome in patients with acute myocardial infarction. However, in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention the importance of elevated heart rate in the very early phase remains unknown. We evaluated the impact of elevated heart rate in the very early pre-hospital phase of ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention on cardiovascular magnetic resonance markers of reperfusion success and clinical outcome. METHODS: In this DANAMI-3 substudy, 1560 ST-segment elevation myocardial infarction patients in sinus rhythm without cardiogenic shock were included in the analyses of clinical outcome and 796 patients underwent cardiovascular magnetic resonance to evaluate area at risk, infarct size and left ventricular ejection fraction. Heart rate was assessed on the first electrocardiogram with ST-elevation (time of diagnosis). RESULTS: Despite equal area at risk (33%±11 versus 36%±16, p=0.174) patients with a pre-hospital heart rate ⩾100 beats per minute developed larger infarcts (19% (interquartile range, 9-17) versus 11% (interquartile range, 10-28), p=0.001) and a lower left ventricular ejection fraction (54%±12 versus 58%±9, p=0.047). Pre-hospital heart rate ⩾100 beats per minute was independently associated with an increased risk of all-cause mortality and heart failure (hazard ratio 2.39 (95% confidence interval 1.58-3.62), p<0.001). CONCLUSIONS: Very early heart rate ⩾100 beats per minute in ST-segment elevation myocardial infarction was independently associated with larger infarct size, reduced left ventricular ejection fraction and an increased risk of all-cause mortality and heart failure, and thus serves as an easily obtainable and powerful tool to identify ST-segment elevation myocardial infarction patients at high risk.

MR-proADM as a Prognostic Marker in Patients With ST-Segment-Elevation Myocardial Infarction-DANAMI-3 (a Danish Study of Optimal Acute Treatment of Patients With STEMI) Substudy.

BACKGROUND: Midregional proadrenomedullin (MR-proADM) has demonstrated prognostic potential after myocardial infarction (MI). Yet, the prognostic value of MR-proADM at admission has not been examined in patients with ST-segment-elevation MI (STEMI). METHODS AND RESULTS: The aim of this substudy, DANAMI-3 (The Danish Study of Optimal Acute Treatment of Patients with ST-segment-elevation myocardial infarction), was to examine the associations of admission concentrations of MR-proADM with short- and long-term mortality and hospital admission for heart failure in patients with ST-segment-elevation myocardial infarction. Outcomes were assessed using Cox proportional hazard models and area under the curve using receiver operating characteristics. In total, 1122 patients were included. The median concentration of MR-proADM was 0.64 nmol/L (25th-75th percentiles, 0.53-0.79). Within 30 days 23 patients (2.0%) died and during a 3-year follow-up 80 (7.1%) died and 38 (3.4%) were admitted for heart failure. A doubling of MR-proADM was, in adjusted models, associated with an increased risk of 30-day mortality (hazard ratio, 2.67; 95% confidence interval, 1.01-7.11; P=0.049), long-term mortality (hazard ratio, 3.23; 95% confidence interval, 1.97-5.29; P<0.0001), and heart failure (hazard ratio, 2.71; 95% confidence interval, 1.32-5.58; P=0.007). For 30-day and 3-year mortality, the area under the curve for MR-proADM was 0.77 and 0.78, respectively. For 3-year mortality, area under the curve (0.84) of the adjusted model marginally changed (0.85; P=0.02) after addition of MR-proADM. CONCLUSIONS: Elevation of admission MR-proADM was associated with long-term mortality and heart failure, whereas the association with short-term mortality was borderline significant. MR-proADM may be a marker of prognosis after ST-segment-elevation myocardial infarction but does not seem to add substantial prognostic information to established clinical models. CLINICAL TRIAL REGISTRATION: URL: http:/www.ClinicalTrials.gov/. Unique identifiers: NCT01435408 and NCT01960933.

Iron Deficiency in COPD Associates with Increased Pulmonary Artery Pressure Estimated by Echocardiography.

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.

Gender Differences in Associations Between Intraprocedural Thrombotic Events During Percutaneous Coronary Intervention and Adverse Outcomes.

Women are frequently reported to have increased morbidity after presentation with acute coronary syndromes and myocardial infarction; however, whether a greater thrombotic tendency contributes to gender differences in clinical outcomes of urgent percutaneous coronary intervention is unknown. Intraprocedural Thrombotic Events (IPTEs) are defined as new or increasing thrombus, abrupt vessel closure, no reflow or slow reflow, or distal embolization at any time during percutaneous coronary intervention. IPTEs were evaluated in this pooled analysis of 6,591 patients with stent implantation and blinded quantitative coronary angiography (QCA) analysis, from the ACUITY and HORIZONS-AMI trials. We compared major adverse cardiac events (MACE) at in-hospital, 30-day, and 1-year follow-up and major bleeding at 30 days according to gender and the presence or absence of IPTE. IPTE was identified in 507 patients (7.7%), with 119 of 1,744 (6.8%) occurring in women and 388 of 4,847 (8.0%) in men (p = 0.12). IPTE, but not gender, was independently associated with MACE at in-hospital and 30-day follow-up. At 1-year follow-up, the adjusted hazard of MACE was higher in women and in patients with IPTE; however, the risk of MACE associated with IPTE was similar among women and men. There was no significant interaction between IPTE and gender for 1-year MACE or 30-day bleeding. IPTE predicted major bleeding only in women. In conclusion, in acute coronary syndromes, women have increased risk of adverse outcome at 1 year. IPTEs are common, occur at similar frequency, and are associated with similar degree of increased MACE in both genders at short- and long-term follow-up. Higher thrombotic propensity does not offer a mechanistic explanation for the worse outcomes noted in women.

Impact of time to treatment on the effects of bivalirudin vs. glycoprotein IIb/IIIa inhibitors and heparin in patients undergoing primary percutaneous coronary intervention: insights from the HORIZONS-AMI trial.

AIMS: In the HORIZONS-AMI trial, bivalirudin compared to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) improved net clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) at the cost of an increased rate of acute stent thrombosis. We sought to examine whether these effects are dependent on time to treatment. METHODS AND RESULTS: The interaction between anticoagulation regimen and symptom onset to first balloon inflation time (SBT) on the 30-day and three-year rates of major adverse cardiac events (MACE) was examined in 3,199 randomised patients according to SBT ≤3 hours versus >3 hours. Among patients with an SBT ≤3 hours, bivalirudin resulted in higher 30-day rates of MACE compared to UFH plus a GPI. Non-significant differences were observed in patients with an SBT >3 hours. Similar results were found for MACE at three years and stent thrombosis and reinfarction at 30 days and three years. By multivariable analysis, bivalirudin was an independent predictor of MACE at 30 days and three years in patients with an SBT ≤3 hours, but not in patients with SBT >3 hours. CONCLUSIONS: Bivalirudin compared to UFH plus a GPI is associated with an increased rate of stent thrombosis and MACE in patients with short SBTs, but not in those with longer SBTs.

Early Stent Thrombosis and Mortality After Primary Percutaneous Coronary Intervention in ST-Segment-Elevation Myocardial Infarction: A Patient-Level Analysis of 2 Randomized Trials.

BACKGROUND: Early stent thrombosis (ST) within 30 days after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction is a serious event. We sought to determine the predictors of and risk of mortality after early ST according to procedural antithrombotic therapy. METHODS AND RESULTS: In a patient-level pooled analysis from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and European Ambulance Acute Coronary Syndrome Angiography (EUROMAX) trials, we examined 30-day outcomes in 4935 patients undergoing primary percutaneous coronary intervention with stent implantation at 188 international sites, randomized to either bivalirudin or heparin±a glycoprotein IIb/IIIa inhibitor (GPI). Early ST occurred in 100 patients (2.0%), 20 of whom (20.0%) died. Bivalirudin was associated with higher rates of early ST compared with heparin±GPI (2.5% versus 1.6%, P=0.04), because of more acute (≤24 h) ST (1.5% versus 0.2%, P<0.0001), with the risk limited to the first 4 hours after percutaneous coronary intervention. The rates of subacute (1-30 days) ST were similar with bivalirudin and heparin±GPI (1.0% versus 1.4%, P=0.24). Among patients with early ST, mortality within 30 days occurred in 4 of 60 (6.7%) bivalirudin-treated patients compared with 16 of 40 (40.0%) heparin±GPI-treated patients (adjusted hazard ratio, 0.12; 95% CI, 0.04-0.39; P=0.0004 and adjusted hazard ratio, 0.122; 95% CI, 0.04-0.39; P=0. 0004). Thus, 30-day mortality attributable to early ST occurred in 4 of 2479 (0.2%) bivalirudin-treated patients versus 16 of 2456 (0.7%) heparin±GPI-treated patients (P=0.007). CONCLUSIONS: In the present large-scale pooled analysis from 2 multicenter randomized trials, early ST was more frequent in patients treated with bivalirudin compared with heparin±GPI because of increased ST within 4 hours after primary percutaneous coronary intervention. However, the mortality attributable to early ST was significantly lower after bivalirudin than after heparin±GPI. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00433966 (HORIZONS-AMI) and NCT01087723 (EUROMAX).

Impact of Hemoglobin A1c Levels on Residual Platelet Reactivity and Outcomes After Insertion of Coronary Drug-Eluting Stents (from the ADAPT-DES Study).

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.

Balancing the Risk of Bleeding and Stroke in Patients With Atrial Fibrillation After Percutaneous Coronary Intervention (from the AVIATOR Registry).

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.

Stroke after transcatheter aortic valve replacement: incidence, risk factors, prognosis, and preventive strategies.

The first transcatheter aortisc valve replacement (TAVR) was performed in 2002, and has been proven beneficial in inoperable and high-risk patients for open heart surgery. Stroke occurrence after TAVR, both periprocedure and at follow-up, has not been well described. We sought to review incidence, pathophysiology, predictors, prognosis, and current preventive strategies of cerebrovascular accidents (CVAs) after TAVR. Studies were selected from a Medline search if they contained clinical outcomes data after TAVR. Acute and subacute CVAs after TAVR have been reported in 3% to 6% of patients. Approximately 45% of CVAs occur within 2 days after TAVR; 28% between 3 and 10 days; 4% between 10 and 30 days; and 10.5% occur from 1 month to 2 years. Clinically silent cerebral embolisms have been reported, with an incidence greatly exceeding that of overt CVAs. Underlying pathophysiologic mechanisms for CVAs can be broadly categorized into embolic and nonembolic causes, as well as procedural and postprocedural (early and late). Important predictors of early CVAs are small aortic valve area, atrial fibrillation, and balloon postdilation, whereas late CVAs are mostly influenced by chronic atrial fibrillation, prior cerebrovascular disease, and transapical approach. Following stroke, patients exhibit increased morbidity and mortality. A multilevel approach for the prevention of CVAs includes improved interventional techniques, embolic protection devices, antithrombotic treatment, close monitoring, and aggressive management of modifiable risk factors. Technology advances notwithstanding stroke morbidity and mortality remains steady. The significance of silent cerebral embolism on prognosis remains uncertain, and optimal medical treatment during and after TAVR should be further investigated.

Long-term outcome of PCI versus CABG in insulin and non-insulin-treated diabetic patients: results from the FREEDOM trial.

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).

Clinical use of the combined Sclarovsky Birnbaum Severity and Anderson Wilkins Acuteness scores from the pre-hospital ECG in ST-segment elevation myocardial infarction.

This review summarizes the electrocardiographic changes during an evolving ST segment elevation myocardial infarction and discusses associated electrocardiographic scores and the potential use of these indices in clinical practice, in particular the ECG scores developed by Anderson and Wilkins estimating the acuteness of myocardial ischemia and Sclarovsky-Birnbaum's grades of ischemia evaluating the severity of ongoing ischemia.