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Background: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in young to middle-aged women.Objectives: We aim to define the long-term natural history of SCAD.Methods: We performed a multicenter, prospective, observational study of patients with nonatherosclerotic SCAD presenting acutely from 22 North American centers. We recorded baseline demographics, in-hospital characteristics, precipitating and predisposing conditions, angiographic features (adjudicated), in-hospital and 3-year major adverse cardiovascular events (MACE). Cox regression multivariable analysis was performed.Results: We prospectively enrolled 750 consecutive patients with SCAD from June 2014 to June 2018. Mean age was 51.7 ± 10.5 years, 88.5% were women (55.0% postmenopausal); 31.3% presented with ST-segment elevation myocardial infarction, and 68.3% with non-ST-segment elevation myocardial infarction. Precipitating emotional stressor was reported in 50.3%, and physical stressor in 28.9%. Predisposing conditions included fibromuscular dysplasia in 42.9% (56.4% in those with complete screening), peripartum state 4.5%, and genetic disorders 1.6%. Most patients were treated conservatively (84.3%); 14.1% underwent percutaneous coronary intervention (PCI), 0.7% coronary artery bypass graft. At 3.0-year median follow-up, mortality was 0.8%, recurrent MI 9.9% (extension of previous SCAD 3.5%, de novo recurrent SCAD 2.4%, iatrogenic dissection 1.9%), with overall MACE 14.0%. Presence of genetic disorders, peripartum SCAD, and extracoronary fibromuscular dysplasia were independent predictors of 3-year MACE. Patients who underwent PCI at index hospitalization had similar postdischarge MACE compared with no PCI. At 3 years, 80.0% remained on aspirin and 73.5% on beta-blockade.Conclusions: Long-term mortality and de novo recurrent SCAD was low in our contemporary large SCAD cohort that included low revascularization rate and high use of beta-blockade and aspirin. Genetic disorders, extracoronary fibromuscular dysplasia, and peripartum SCAD were independent predictors of long-term MACE. [ABSTRACT FROM AUTHOR]

Background: Shift work is associated with increased risk of acute myocardial infarction (AMI) and worsened prognosis. However, the mechanisms linking shift work and worsened prognosis in AMI remain unclear.Objectives: This study sought to investigate the impact of shift work on reperfusion injury, a major determinant of clinical outcomes in AMI.Methods: Study patient data were obtained from the database of the EARLY-MYO-CMR (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI) registry, which was a prospective, multicenter registry of patients with ST-segment elevation myocardial infarction (STEMI) undergoing cardiac magnetic resonance (CMR) imaging after reperfusion therapy. The primary endpoint was CMR-defined post-reperfusion infarct size. A secondary clinical endpoint was the composite of major adverse cardiac events (MACE) during follow-up. Potential mechanisms were explored with the use of preclinical animal AMI models.Results: Of 706 patients enrolled in the EARLY-MYO-CMR registry, 412 patients with STEMI were ultimately included. Shift work was associated with increased CMR-defined infarct size (β = 5.94%; 95% CI: 2.94-8.94; P < 0.0001). During a median follow-up of 5.0 years, shift work was associated with increased risks of MACE (adjusted HR: 1.92; 95% CI: 1.12-3.29; P = 0.017). Consistent with clinical findings, shift work simulation in mice and sheep significantly augmented reperfusion injury in AMI. Mechanism studies identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that played a crucial role in mediating the detrimental effects of shift work on myocardial injury.Conclusions: The current study provided novel findings that shift work increases myocardial infarction reperfusion injury. It identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that might play a crucial role in mediating this process. (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI [EARLY-MYO-CMR] registry; NCT03768453). [ABSTRACT FROM AUTHOR]

Background: The residual lifetime risk (RLR) of developing heart failure (HF) may have changed over time because of the increasing population burden of hypertension, obesity, and diabetes; greater survival after myocardial infarction; and a greater lifespan.Objectives: The authors assessed changes in the RLR for HF in two 25-year epochs (1965-1989 and 1990-2014).Methods: We compared the RLR of HF at age 50 years (adjusting for competing risk of death) in the 2 epochs in Framingham Study participants overall and in the following strata: sex, body mass index, blood pressure, and diabetes.Results: Mean life expectancy increased from 75.9 to 82.1 years in women and 72.5 to 78.1 years in men. We observed 624 HF events over 111,351 person-observations in epoch 1, and 875 HF events over 128,903 person-observations in epoch 2. The mean age at onset of HF increased across the epochs by 6.6 years (women) to 7.2 years (men). The RLR of HF at age 50 years increased across epochs from 18.86% to 22.55% (absolute increase 3.69; 95% CI: 0.90-6.49; P = 0.01) in women, and from 19.19% to 25.25% (absolute increase 6.06; 95% CI: 3.08-9.04; P < 0.001) in men. The increase in RLR of HF in the second epoch was consistent across strata with excess body mass index or higher blood pressure (relative increase of 28%-47%) and in participants without prior myocardial infarction (relative increase of 23%).Conclusions: The RLR of HF has increased in our community-based sample of White individuals over the last 5 decades, possibly caused by an increase in life expectancy. [ABSTRACT FROM AUTHOR]

Background: Benefits of intensive blood pressure lowering on health outcomes have been demonstrated in high-risk patients. However, little is known about such benefits in patients with left ventricular hypertrophy (LVH).Objectives: This study sought to investigate the association of on-treatment blood pressure with cardiovascular disease (CVD) risk in adults with hypertension and LVH.Methods: From a nationwide health examination database, this study identified 95,545 participants aged 40-79 years who were taking antihypertensive medication and had LVH on baseline electrocardiography. Using Cox models, HRs and 95% CIs for CVD events were calculated according to systolic blood pressure (SBP) or diastolic blood pressure (DBP).Results: Over a median follow-up of 11.5 years, 12,035 new CVD events occurred. An SBP of <130 mm Hg and DBP of <80 mm Hg were associated with the lowest risk for CVD events in cubic spline models. When the group with SBP of 120-129 mm Hg was the reference, multivariable-adjusted HRs were 1.31 (95% CI: 1.24-1.38) in the ≥140 mm Hg group, 1.08 (95% CI: 1.02-1.15) in the 130-139 mm Hg group, and 1.03 (95% CI: 0.93-1.15) in the <120 mm Hg group. Likewise, when the group with DBP of 70-79 mm Hg was the reference, multivariable-adjusted HRs were 1.30 (95% CI: 1.24-1.37) in the ≥90 mm Hg group, 1.06 (95% CI: 1.01-1.12) in the 80-89 mm Hg group, and 1.08 (95% CI: 0.96 to 1.20) in the <70 mm Hg group.Conclusions: In adults with hypertension and LVH, the risk for CVD events was the lowest at SBP <130 mm Hg and DBP <80 mm Hg. Further randomized trials are warranted to establish optimal blood pressure-lowering strategies for these patients. [ABSTRACT FROM AUTHOR]

Background: Patients with suspected acute coronary syndrome in whom myocardial infarction has been excluded are at risk of future adverse cardiac events.Objectives: This study evaluated the usefulness of high-sensitivity cardiac troponin I (hs-cTnI) to select patients for further investigation after myocardial infarction has been excluded.Methods: This is a prospective cohort study of patients presenting to the emergency department with suspected acute coronary syndrome and hs-cTnI concentrations below the sex-specific 99th percentile. Patients were recruited in a 2:1 fashion, stratified by peak hs-cTnI concentration above and below the risk stratification threshold of 5 ng/L. All patients underwent coronary computed tomography angiography (CCTA) after hospital discharge.Results: Overall, 250 patients were recruited (61.4 ± 12.2 years 31% women) in whom 62.4% (156 of 250 patients) had coronary artery disease (CAD). Patients with intermediate hs-cTnI concentrations (between 5 ng/L and the sex-specific 99th percentile) were more likely to have CAD than those with hs-cTnI concentrations <5 ng/L (71.9% [120 of 167 patients] vs 43.4% [36 of 83 patients]; odds ratio: 3.33; 95% CI: 1.92-5.78). Conversely, there was no association between anginal symptoms and CAD (63.2% [67 of 106 patients] vs 61.8% [89 of 144 patients]; odds ratio: 0.92; 95% CI: 0.48-1.76). Most patients with CAD did not have a previous diagnosis (53.2%; 83 of 156 patients) and were not on antiplatelet and statin therapies (63.5%; 99 of 156 patients) before they underwent CCTA.Conclusions: In patients who had myocardial infarction excluded, CAD was 3× more likely in those with intermediate hs-cTnI concentrations compared with low hs-cTnI concentrations. In such patients, CCTA could help to identify those with occult CAD and to target preventative treatments, thereby improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Discrimination among patients with type 1 myocardial infarction (T1MI), type 2 myocardial infarction (T2MI), and myocardial injury is difficult.Objectives: The aim of this study was to investigate the discriminative value of a 29-biomarker panel in an emergency department setting.Methods: Patients presenting with suspected myocardial infarction (MI) were recruited. The final diagnosis in all patients was adjudicated on the basis of the fourth universal definition of MI. A panel of 29 biomarkers was measured, and multivariable logistic regression analysis was used to evaluate the associations of these biomarkers with the diagnosis of MI or myocardial injury. Biomarkers were chosen using backward selection. The model was internally validated using bootstrapping.Results: Overall, 748 patients were recruited (median age 64 years), of whom 138 had MI (107 T1MI and 31 T2MI) and 221 had myocardial injury. In the multivariable model, 4 biomarkers (apolipoprotein A-II, N-terminal prohormone of brain natriuretic peptide, copeptin, and high-sensitivity cardiac troponin I) remained significant discriminators between T1MI and T2MI. Internal validation of the model showed an area under the curve of 0.82. For discrimination between MI and myocardial injury, 6 biomarkers (adiponectin, N-terminal prohormone of brain natriuretic peptide, pulmonary and activation-regulated chemokine, transthyretin, copeptin, and high-sensitivity troponin I) were selected. Internal validation showed an area under the curve of 0.84.Conclusions: Among 29 biomarkers, 7 were identified to be the most relevant discriminators between subtypes of MI or myocardial injury. Regression models based on these biomarkers allowed good discrimination. (Biomarkers in Acute Cardiac Care [BACC]; NCT02355457). [ABSTRACT FROM AUTHOR]

Background: Standardization of risk is critical in benchmarking and quality improvement efforts for percutaneous coronary interventions (PCIs). In 2018, the CathPCI Registry was updated to include additional variables to better classify higher-risk patients.Objectives: This study sought to develop a model for predicting in-hospital mortality risk following PCI incorporating these additional variables.Methods: Data from 706,263 PCIs performed between July 2018 and June 2019 at 1,608 sites were used to develop and validate a new full and pre-catheterization model to predict in-hospital mortality, and a simplified bedside risk score. The sample was randomly split into a development cohort (70%, n = 495,005) and a validation cohort (30%, n = 211,258). The authors created 1,000 bootstrapped samples of the development cohort and used stepwise selection logistic regression on each sample. The final model included variables that were selected in at least 70% of the bootstrapped samples and those identified a priori due to clinical relevance.Results: In-hospital mortality following PCI varied based on clinical presentation. Procedural urgency, cardiovascular instability, and level of consciousness after cardiac arrest were most predictive of in-hospital mortality. The full model performed well, with excellent discrimination (C-index: 0.943) in the validation cohort and good calibration across different clinical and procedural risk cohorts. The median hospital risk-standardized mortality rate was 1.9% and ranged from 1.1% to 3.3% (interquartile range: 1.7% to 2.1%).Conclusions: The risk of mortality following PCI can be predicted in contemporary practice by incorporating variables that reflect clinical acuity. This model, which includes data previously not captured, is a valid instrument for risk stratification and for quality improvement efforts. [ABSTRACT FROM AUTHOR]

Background: Patients with chest pain are often evaluated for acute myocardial infarction through troponin testing, which may prompt downstream services (cascades) of uncertain value.Objectives: This study sought to determine the association of high-sensitivity cardiac troponin (hs-cTn) assay implementation with cascade events.Methods: Using electronic health record and billing data, this study examined patient-visits to 5 emergency departments from April 1, 2017, to April 1, 2019. Difference-in-differences analysis compared patient-visits for chest pain (n = 7,564) to patient-visits for other symptoms (n = 100,415) (irrespective of troponin testing) before and after hs-cTn assay implementation. Outcomes included presence of any cascade event potentially associated with an initial hs-cTn test (primary), individual cascade events, length of stay, and spending on cardiac services.Results: Following hs-cTn implementation, patients with chest pain had a 2.8% (95% confidence interval [CI]: 0.72% to 4.9%) net increase in experiencing any cascade event. They were more likely to have multiple troponin tests (10.5%; 95% CI: 9.0% to 12.0%) and electrocardiograms (7.1 per 100 patient-visits; 95% CI: 1.8 to 12.4). However, they received net fewer computed tomography scans (-1.5 per 100 patient-visits; 95% CI: -1.8 to -1.1), stress tests (-5.9 per 100 patient-visits; 95% CI: -6.5 to -5.3), and percutaneous coronary intervention (PCI) (-0.65 per 100 patient-visits; 95% CI: -1.01 to -0.30) and were less likely to receive cardiac medications, undergo cardiology evaluation (-3.5%; 95% CI: -4.5% to 2.6%), or be hospitalized (-5.8%; 95% CI: -7.7% to -3.8%). Patients with chest pain had lower net mean length of stay (-0.24 days; 95% CI: -0.32 to -0.16) but no net change in spending.Conclusions: Hs-cTn assay implementation was associated with more net upfront tests yet fewer net stress tests, PCI, cardiology evaluations, and hospital admissions in patients with chest pain relative to patients with other symptoms. [ABSTRACT FROM AUTHOR]

Background: Among patients with acute coronary syndrome following transcatheter aortic valve replacement (TAVR), those presenting with ST-segment elevation myocardial infarction (STEMI) are at highest risk.Objectives: The goal of this study was to determine the clinical characteristics, management, and outcomes of STEMI after TAVR.Methods: This was a multicenter study including 118 patients presenting with STEMI at a median of 255 days (interquartile range: 9 to 680 days) after TAVR. Procedural features of STEMI after TAVR managed with primary percutaneous coronary intervention (PCI) were compared with all-comer STEMI: 439 non-TAVR patients who had primary PCI within the 2 weeks before and after each post-TAVR STEMI case in 5 participating centers from different countries.Results: Median door-to-balloon time was higher in TAVR patients (40 min [interquartile range: 25 to 57 min] vs. 30 min [interquartile range: 25 to 35 min]; p = 0.003). Procedural time, fluoroscopy time, dose-area product, and contrast volume were also higher in TAVR patients (p < 0.01 for all). PCI failure occurred more frequently in patients with previous TAVR (16.5% vs. 3.9%; p < 0.001), including 5 patients in whom the culprit lesion was not revascularized owing to coronary ostia cannulation failure. In-hospital and late (median of 7 months [interquartile range: 1 to 21 months]) mortality rates were 25.4% and 42.4%, respectively (20.6% and 38.2% in primary PCI patients), and estimated glomerular filtration rate <60 ml/min (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.42 to 6.43; p = 0.004), Killip class ≥2 (HR: 2.74; 95% CI: 1.37 to 5.49; p = 0.004), and PCI failure (HR: 3.23; 95% CI: 1.42 to 7.31; p = 0.005) determined an increased risk.Conclusions: STEMI after TAVR was associated with very high in-hospital and mid-term mortality. Longer door-to-balloon times and a higher PCI failure rate were observed in TAVR patients, partially due to coronary access issues specific to the TAVR population, and this was associated with poorer outcomes. [ABSTRACT FROM AUTHOR]

Background: Evidence from prospective studies has suggested that long working hours are associated with incident coronary heart disease (CHD) events. However, no previous study has examined whether long working hours are associated with an increased risk of recurrent CHD events among patients returning to work after a first myocardial infarction (MI).Objectives: The purpose of this study was to examine the effect of long working hours on the risk of recurrent CHD events.Methods: This is a prospective cohort study of 967 men and women age 35 to 59 years who returned to work after a first MI. Patients were recruited from 30 hospitals across the province of Quebec, Canada. The mean follow-up duration was 5.9 years. Long working hours were assessed on average 6 weeks after their return to work. Incident CHD events (fatal or nonfatal MI and unstable angina) occurring during follow-up were determined using patients' medical files. Hazard ratios were estimated using Cox proportional hazard regression models. Splines and fractional polynomial regressions were used for flexible exposure and time modeling.Results: Recurrent CHD events occurred among 205 patients. Participants working long hours (≥55 h/week) had a higher risk of recurrent CHD events after controlling for sociodemographics, lifestyle-related risk factors, clinical risk factors, work environment factors, and personality factors (hazard ratio vs. 35 to 40 h/week: 1.67; 95% confidence interval: 1.10 to 2.53). These results showed a linear risk increase after 40 h/week and a stronger effect after the first 4 years of follow-up and when long working hours are combined with job strain.Conclusions: Among patients returning to work after a first MI, longer working hours per week is associated with an increased risk of recurrent CHD events. Secondary prevention interventions aiming to reduce the number of working hours among these patients may lower the risk of CHD recurrence. [ABSTRACT FROM AUTHOR]

Background: Phosphodiesterase 5 inhibitor (PDE5i) treatment is associated with reduced mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI).Objectives: This study sought to investigate the association between treatment with PDE5i or alprostadil and outcomes in men with stable coronary artery disease.Methods: All Swedish men with a prior MI or revascularization who received PDE5i or alprostadil during 2006 through 2013 at >6 months after the event were included, using the Swedish Patient Register and the Swedish Prescribed Drug Register. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals for all-cause mortality, MI, heart failure, cardiovascular mortality, noncardiovascular mortality, cardiac revascularization, peripheral arterial disease, and stroke in men treated with PDE5i versus alprostadil.Results: This study included 16,548 men treated with PDE5i and 1,994 treated with alprostadil. The mean follow-up was 5.8 years, with 2,261 deaths (14%) in the PDE5i group and 521 (26%) in the alprostadil group. PDE5i compared with alprostadil treatment was associated with lower mortality (hazard ratio: 0.88; 95% confidence interval: 0.79 to 0.98) and with similar associations for MI, heart failure, cardiovascular mortality, and revascularization. When quintiles (q) of filled PDE5i prescriptions were compared using q1 as reference, patients in q3, q4, and q5 had lower all-cause mortality. Among alprostadil users, those in q5 had a lower all-cause mortality compared to q1.Conclusions: In men with stable coronary artery disease, treatment with PDE5i is associated with lower risks of death, MI, heart failure, and revascularization compared with alprostadil treatment. Although the decrease in all-cause mortality was PDE5i dose dependent, the data do not permit the inference of causality or any clinical benefits of PDE5i because of the observational study design. [ABSTRACT FROM AUTHOR]

Background: Patients with obstructive coronary artery disease (CAD) are at high risk for cardiovascular disease (CVD) events. However, it remains unclear whether the high risk is due to high atherosclerotic disease burden or if presence of stenosis has independent predictive value.Objectives: The purpose of this study was to evaluate if obstructive CAD provides predictive value beyond its association with total calcified atherosclerotic plaque burden as assessed by coronary artery calcium (CAC).Methods: Among 23,759 symptomatic patients from the Western Denmark Heart Registry who underwent diagnostic computed tomography angiography (CTA), we assessed the risk of major CVD (myocardial infarction, stroke, and all-cause death) stratified by CAC burden and number of vessels with obstructive disease.Results: During a median follow-up of 4.3 years, 1,054 patients experienced a first major CVD event. The event rate increased stepwise with both higher CAC scores and number of vessels with obstructive disease (by CAC scores: 6.2 per 1,000 person-years (PY) for CAC = 0 to 42.3 per 1,000 PY for CAC >1,000; by number of vessels with obstructive disease: 6.1 per 1,000 PY for no CAD to 34.7 per 1,000 PY for 3-vessel disease). When stratified by 5 groups of CAC scores (0, 1 to 99, 100 to 399, 400 to 1,000, and >1,000), the presence of obstructive CAD was not associated with higher risk than presence of nonobstructive CAD.Conclusions: Plaque burden, not stenosis per se, is the main predictor of risk for CVD events and death. Thus, patients with a comparable calcified atherosclerosis burden generally carry a similar risk for CVD events regardless of whether they have nonobstructive or obstructive CAD. [ABSTRACT FROM AUTHOR]

Background: Plasma apolipoprotein B (apoB) is a composite measure of all apoB-containing lipoproteins causing atherosclerotic cardiovascular disease; however, it is unclear which fraction of risk is explained by cholesterol and triglycerides, respectively, in very low-density lipoproteins (VLDLs).Objectives: The authors tested the hypothesis that VLDL cholesterol and triglycerides each explain part of the myocardial infarction risk from apoB-containing lipoproteins.Methods: Nested within 109,751 individuals from the Copenhagen General Population Study, the authors examined 25,480 subjects free of lipid-lowering therapy and myocardial infarction at study entry. All had measurements of plasma apoB (quantitating number of apoB-containing lipoproteins) and cholesterol and triglyceride content of VLDL, intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs).Results: During a median 11 years of follow-up, 1,816 were diagnosed with myocardial infarction. Per 1-mmol/l higher levels, multivariable-adjusted hazard ratios for myocardial infarction were 2.07 (95% confidence interval [CI]: 1.81 to 2.36) for VLDL cholesterol, 1.19 (95% CI: 1.14 to 1.25) for VLDL triglycerides, 5.38 (95% CI: 3.73 to 7.75) for IDL cholesterol, and 1.86 (95% CI: 1.62 to 2.14) for LDL cholesterol. Per 1-g/l higher plasma apoB, the corresponding value was 2.21 (95% CI: 1.90 to 2.58). In a step-up Cox regression, risk factors for myocardial infarction entered by importance as VLDL cholesterol, systolic blood pressure, smoking, and IDL + LDL cholesterol, whereas VLDL triglycerides did not enter the model. VLDL cholesterol explained 50% and IDL + LDL cholesterol 29% of the risk of myocardial infarction from apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk.Conclusions: VLDL cholesterol explained one-half of the myocardial infarction risk from elevated apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk. [ABSTRACT FROM AUTHOR]

Background: Varying definitions of procedural myocardial infarction (PMI) are in widespread use.Objectives: This study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) surgery in the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial.Methods: The pre-specified protocol definition of PMI (PMIProt) required a large elevation of creatine kinase-MB (CK-MB), with identical threshold for both procedures. The Third Universal Definition of MI (types 4a and 5) (PMIUD) required lesser biomarker elevations but with supporting evidence of myocardial ischemia, different after PCI and CABG. For the PMIUD, troponins were used preferentially (available in 49.5% of patients), CK-MB otherwise. The multivariable relationship between each PMI type and 5-year mortality was determined.Results: PMIProt occurred in 34 of 935 (3.6%) patients after PCI and 56 of 923 (6.1%) patients after CABG (difference -2.4%; 95% confidence interval [CI]: -4.4% to -0.5%; p = 0.015). The corresponding rates of PMIUD were 37 (4.0%) and 20 (2.2%), respectively (difference 1.8%; 95% CI: 0.2% to 3.4%; p = 0.025). Both PMIProt and PMIUD were associated with 5-year cardiovascular mortality (adjusted hazard ratio [HR]: 2.18 [95% CI: 1.13 to 4.23] and 2.87 [95% CI: 1.44 to 5.73], respectively). PMIProt was associated with a consistent hazard of cardiovascular mortality after both PCI and CABG (pinteraction = 0.86). Conversely, PMIUD was strongly associated with cardiovascular mortality after CABG (adjusted HR: 11.94; 95% CI: 4.84 to 29.47) but not after PCI (adjusted HR: 1.14; 95% CI: 0.35 to 3.67) (pinteraction = 0.004). Results were similar for all-cause mortality and with varying PMIUD biomarker definitions. Only large biomarker elevations (CK-MB ≥10× upper reference limit and troponin ≥70× upper reference limit) were associated with mortality.Conclusions: The rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMIProt was associated with similar hazard after PCI and CABG, whereas PMIUD was strongly associated with mortality after CABG but not after PCI. (EXCEL Clinical Trial [EXCEL]; NCT01205776). [ABSTRACT FROM AUTHOR]

Background: Inflammation reduction with the interleukin (IL)-1β inhibitor canakinumab significantly reduces the first major adverse cardiovascular event in patients with prior myocardial infarction (MI) and residual inflammatory risk (high-sensitivity C-reactive protein ≥ 2 mg/l). However, the effect of canakinumab on the total number of cardiovascular events, including recurrent events collected after a first event, is unknown.Objectives: This study sought to determine whether randomly allocated canakinumab would reduce the total burden of serious cardiovascular events.Methods: We randomized 10,061 patients to placebo or canakinumab 50 mg, 150 mg, or 300 mg once every 3 months and compared the rates of the composite of all serious cardiovascular events (MI, stroke, coronary revascularization, and cardiovascular death) in active versus placebo groups. We used negative binomial regression to account for correlations among repeated events in the same person and to estimate rate ratios and 95% confidence intervals.Results: During a median of 3.7 years of follow-up, 3,417 total serious cardiovascular events occurred in 2,003 individuals among the 10,061 unique patients randomized. Canakinumab reduced the rates of total serious cardiovascular events, with rates per 100 person-years in the placebo, 50 mg, 150 mg, and 300 mg canakinumab groups of 10.4, 8.4, 8.3, and 8.2, respectively. The corresponding rate ratios (95% confidence intervals) compared with placebo were 0.80 (0.69 to 0.93) for 50 mg, 0.79 (0.68 to 0.92) for 150 mg, and 0.78 (0.67 to 0.91) for 300 mg.Conclusions: Anti-inflammatory therapy with canakinumab significantly reduced the total number of cardiovascular events in patients with prior MI and evidence of residual inflammatory risk. (Cardiovascular Risk Reduction Study [Reduction in Recurrent Major CV Disease Events] (CANTOS); NCT01327846. [ABSTRACT FROM AUTHOR]

Background: Limited data are available regarding the risk for adverse clinical events with concomitant nonsteroidal anti-inflammatory drug (NSAID) treatment after myocardial infarction (MI).Objectives: The aim of this study was to investigate the risk for cardiovascular and bleeding events according to groups of antithrombotic medications and subtypes of NSAIDs in patients with MI.Methods: This was a nationwide cohort study to enroll a study population from the Health Insurance Review and Assessment Service database in Korea between 2009 and 2013. Patients were divided into groups on the basis of the prescribed antithrombotic medications. The primary and secondary outcomes were thromboembolic cardiovascular and clinically relevant bleeding events. The risk for adverse clinical events was assessed by ongoing NSAID treatment and subtypes of NSAIDs.Results: In total, 108,232 patients (mean age 64.2 ± 12.8 years, 72.1% men, mean follow-up duration 2.3 ± 1.8 years) with first diagnosed MI were enrolled. Concomitant NSAID treatment significantly increased the risk for cardiovascular events (hazard ratio [HR]: 6.96; 95% confidence interval [CI]: 6.24 to 6.77; p < 0.001) and bleeding events (HR: 4.08; 95% CI: 3.51 to 4.73; p < 0.001) compared with no NSAID treatment. Among NSAID subtypes, the risk for cardiovascular and bleeding events was lowest with the use of celecoxib (HR: 4.65; 95% CI: 3.17 to 6.82; p < 0.001, and 3.44; 95% CI: 2.20 to 5.39; p < 0.001, respectively) and meloxicam (HR: 3.03; 95% CI: 1.68 to 5.47; p < 0.001, and 2.80; 95% CI: 1.40 to 5.60; p < 0.001, respectively).Conclusions: Concomitant NSAID treatment significantly increased the risk for cardiovascular and bleeding events after MI. Although NSAID treatment should be avoided after MI, celecoxib and meloxicam could be considered as alternative options in cases in which NSAID use is unavoidable. [ABSTRACT FROM AUTHOR]

Background: Oral P2Y12 receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y12 receptor antagonist with a rapid onset and short duration of action.Objectives: This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI.Methods: Patients with AMI were randomized to a single subcutaneous dose of selatogrel of 8 or 16 mg. The primary endpoint was response to treatment (P2Y12 reaction units <100; measured by VerifyNow) at 30 min post-dose. Safety was assessed up to 48 h post-injection.Results: Forty-seven patients received selatogrel 8 mg (n = 24) or 16 mg (n = 23) followed by ticagrelor (n = 43) or clopidogrel (n = 1). The proportion of responders 30 min post-dose was 91% (one-sided 97.5% confidence interval [CI]: 80% to 100%) and 96% (97.5% CI: 87% to 100%) with 8 and 16 mg, respectively (p values for responders >85% target; p = 0.142 and p = 0.009, respectively). Response rates were independent from type of AMI presentation, age, or sex. A similar response rate was observed at 15 min (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 91% [97.5% CI: 80% to 100%]), which was sustained at 60 min post-dose (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 96% [97.5% CI: 87% to 100%]). At 15 min, median P2Y12 reaction units was 51 (range: 4 to 208) for 8 mg and 9 (range: 2 to 175) for 16 mg. Selatogrel was well tolerated, without major bleeding complications.Conclusions: Single-dose subcutaneous administration of selatogrel in patients with AMI was safe and induced a profound, rapid, and dose-related antiplatelet response. (A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Heart Attack; NCT03487445, 2018-000765-36 [EudraCT]). [ABSTRACT FROM AUTHOR]

Background: Whether a regimen of ticagrelor monotherapy attenuates bleeding complications without increasing ischemic risk in patients undergoing complex percutaneous coronary intervention (PCI) is unknown.Objectives: The purpose of this study was to evaluate the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing complex PCI from the randomized, double-blind, placebo-controlled TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial.Methods: In the TWILIGHT trial, after 3 months of ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. Complex PCI was defined as any of the following: 3 vessels treated, ≥3 lesions treated, total stent length >60 mm, bifurcation with 2 stents implanted, atherectomy device use, left main PCI, surgical bypass graft or chronic total occlusion as target lesions. Bleeding and ischemic endpoints were evaluated at 1 year after randomization.Results: Among 7,119 patients randomized in the main trial, complex PCI was performed in 2,342 patients. Compared to ticagrelor plus aspirin, ticagrelor plus placebo resulted in significantly lower rates of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (4.2% vs. 7.7%; hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.38 to 0.76). BARC type 3 or 5 bleeding was also significantly reduced (1.1% vs. 2.6%; HR: 0.41; 95% CI: 0.21 to 0.80). There were no significant between-group differences in death, myocardial infarction, or stroke (3.8% vs. 4.9%; HR: 0.77; 95% CI: 0.52 to 1.15), nor in stent thrombosis.Conclusions: Among patients undergoing complex PCI who initially completed 3 months of ticagrelor plus aspirin, continuation of ticagrelor monotherapy was associated with lower incidence of bleeding without increasing the risk of ischemic events compared to continuing ticagrelor plus aspirin. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242). [ABSTRACT FROM AUTHOR]

Background: P2Y12 inhibitor monotherapy with ticagrelor after a brief period of dual antiplatelet therapy can reduce bleeding without increasing ischemic harm after percutaneous coronary intervention (PCI). The impact of this approach among patients with diabetes mellitus (DM) remains unknown.Objectives: The purpose of this study was to examine the effect of ticagrelor monotherapy versus ticagrelor plus aspirin among patients with DM undergoing PCI.Methods: This was a pre-specified analysis of the DM cohort in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial. After 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The primary endpoint was Bleeding Academic Research Consortium 2, 3, or 5 bleeding. The composite ischemic endpoint was all-cause death, myocardial infarction, or stroke.Results: Patients with DM comprised 37% (n = 2,620) of the randomized cohort and were characterized by more frequent comorbidities and a higher prevalence of multivessel disease. The incidence of Bleeding Academic Research Consortium 2, 3, or 5 bleeding was 4.5% and 6.7% among patients with DM randomized to ticagrelor plus placebo versus ticagrelor plus aspirin (hazard ratio: 0.65; 95% confidence interval: 0.47 to 0.91; p = 0.012). Ticagrelor monotherapy was not associated with an increase in ischemic events compared with ticagrelor plus aspirin (4.6% vs. 5.9%; hazard ratio: 0.77; 95% confidence interval: 0.55 to 1.09; p = 0.14). In the overall trial population, there was no significant interaction between DM status and treatment group for the primary bleeding or ischemic endpoints.Conclusions: Compared with ticagrelor plus aspirin, the effect of ticagrelor monotherapy in reducing the risk of clinically relevant bleeding without any increase in ischemic events was consistent among patients with or without DM undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242). [ABSTRACT FROM AUTHOR]

Background: Autopsy studies suggest that implanting stents in lipid-rich plaque (LRP) may be associated with adverse outcomes.Objectives: The purpose of this study was to evaluate the association between LRP detected by near-infrared spectroscopy (NIRS) and clinical outcomes in patients with coronary artery disease treated with contemporary drug-eluting stents.Methods: In this prospective, multicenter registry, NIRS was performed in patients undergoing coronary angiography and possible percutaneous coronary intervention (PCI). Lipid core burden index (LCBI) was calculated as the fraction of pixels with the probability of LRP >0.6 within a region of interest. MaxLCBI4mm was defined as the maximum LCBI within any 4-mm-long segment. Major adverse cardiac events (MACE) included cardiac death, myocardial infarction, definite or probable stent thrombosis, or unplanned revascularization or rehospitalization for progressive angina or unstable angina. Events were subcategorized as culprit (treated) lesion-related, nonculprit (untreated) lesion-related, or indeterminate.Results: Among 1,999 patients who were enrolled in the COLOR (Chemometric Observations of Lipid Core Plaques of Interest in Native Coronary Arteries Registry), PCI was performed in 1,621 patients and MACE occurred in 18.0% of patients, of which 8.3% were culprit lesion-related, 10.7% were nonculprit lesion-related, and 3.1% were indeterminate during 2-year follow-up. Complications from NIRS imaging occurred in 9 patients (0.45%), which resulted in 1 peri-procedural myocardial infarction and 1 emergent coronary bypass. Pre-PCI NIRS imaging was obtained in 1,189 patients, and the 2-year rate of culprit lesion-related MACE was not significantly associated with maxLCBI4mm (hazard ratio of maxLCBI4mm per 100: 1.06; 95% confidence interval: 0.96 to 1.17; p = 0.28) after adjusting clinical and procedural factors.Conclusions: Following PCI with contemporary drug-eluting stents, stent implantation in NIRS-defined LRPs was not associated with increased periprocedural or late adverse outcomes compared with those without significant lipid. [ABSTRACT FROM AUTHOR]

Background: Recent emphasis on reduced duration and/or intensity of antiplatelet therapy following percutaneous coronary intervention (PCI) irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients.Objectives: The authors sought to examine the effect of more potent antiplatelet therapy on the basis of the timing and etiology of recurrent myocardial infarction (MI) or cardiovascular death following PCI for ACS.Methods: In the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38), which randomized patients to prasugrel or clopidogrel, 12,844 patients with ACS received at least 1 stent. MI and cardiovascular death were categorized as: 1) procedural (related to revascularization); 2) definite or probable stent thrombosis (ST); or 3) spontaneous (non-ST or non-procedure-related). Median follow-up was 14.5 months.Results: Among the first events occurring within 30 days, 584 (69.0%) were procedural, 126 (14.9%) ST-related, and 136 (16.1%) spontaneous. After 30 days, 22 (4.7%) were procedural, 63 (13.5%) were ST-related, and 383 (81.8%) spontaneous. Prasugrel significantly reduced the incidence of MI or cardiovascular death for ST-related (1.0% vs. 2.1%; p < 0.001) and spontaneous events (3.9% vs. 4.8%; p = 0.012), with a directionally consistent numerical reduction for procedural events (4.4% vs. 5.1%; p = 0.078). Prasugrel increased spontaneous, but not procedural, major bleeding.Conclusions: Long-term potent antithrombotic therapy reduces de novo (spontaneous) atherothrombotic events in addition to preventing complications associated with stenting of the culprit lesion following ACS. In patients undergoing PCI for ACS, spontaneous events predominate after 30 days, with the later-phase cardiovascular benefit of potent dual antiplatelet therapy driven largely by reducing de novo atherothrombotic ischemic events. (Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591). [ABSTRACT FROM AUTHOR]

Background: Until now, high-sensitivity cardiac troponin (hs-cTn) assays were mainly developed for large central laboratory platforms.Objectives: This study aimed to assess the clinical performance of a point-of-care (POC)-hs-cTnI assay in patients with suspected myocardial infarction (MI).Methods: This study enrolled patients presenting to the emergency department with symptoms suggestive of MI. Two cardiologists centrally adjudicated the final diagnosis using all clinical data including cardiac imaging. The primary objective was to directly compare diagnostic accuracy of POC-hs-cTnI-TriageTrue versus best-validated central laboratory assays. Secondary objectives included the derivation and validation of a POC-hs-cTnI-TriageTrue-specific 0/1-h algorithm.Results: MI was the adjudicated final diagnosis in 178 of 1,261 patients (14%). The area under the curve (AUC) for POC-hs-cTnI-TriageTrue at presentation was 0.95 (95% confidence interval [CI]: 0.93 to 0.96) and was at least comparable to hs-cTnT-Elecsys (AUC: 0.94; 95% CI: 0.93 to 0.96; p = 0.213) and hs-cTnI-Architect (AUC: 0.92; 95% CI: 0.90 to 0.93; p < 0.001). A single cutoff concentration <3 ng/l at presentation identified 45% of patients at low risk with a negative predictive value (NPV) of 100% (95% CI: 99.4% to 100%). A single cutoff concentration >60 ng/l identified patients at high risk with a positive predictive value (PPV) of 76.8% (95% CI: 68.9% to 83.6%). The 0/1-h algorithm ruled out 55% of patients (NPV: 100%; 95% CI: 98.8% to 100%), and ruled in 18% of patients (PPV: 76.8%; 95% CI: 67.2% to 84.7%). Ruled-out patients had cumulative event rates of 0% at 30 days and 1.6% at 2 years. This study confirmed these findings in a secondary analysis including hs-cTnI-Architect for central adjudication.Conclusions: The POC-hs-cTnI-TriageTrue assay provides high diagnostic accuracy in patients with suspected MI with a clinical performance that is at least comparable to that of best-validated central laboratory assays. (Advantageous Predictors of Acute Coronary Syndromes Evaluation Study [APACE]; NCT00470587). [ABSTRACT FROM AUTHOR]

Background: In the ACCOAST (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction) trial, the prasugrel pre-treatment strategy versus placebo was associated with excess bleeding complications and no improved ischemic outcome in non-ST-segment elevation myocardial infarction (MI). Whether patients with the longest pre-treatment duration had an ischemic benefit is unknown.Objectives: This pre-specified analysis of the ACCOAST trial aimed to assess the effect of pre-treatment duration with prasugrel (time from randomization to angiography) on outcomes.Methods: Within the 4,033 patients randomized in the ACCOAST trial, pre-treatment duration was available in 4,001 patients (99.2%). The population of the trial was divided into quartiles of pre-treatment duration (0.1 to 2.5 h, 2.5 to 3.9 h, 3.9 to 13.6 h, and >13.6 h) with an evaluation of the primary efficacy endpoint of cardiovascular death, MI, stroke, urgent revascularization or glycoprotein IIb/IIIa inhibitor bailout use. Secondary efficacy outcomes including cardiovascular death, MI, or stroke; all-cause death; stent thrombosis and safety outcomes (all coronary artery bypass graft [CABG] or non-CABG TIMI [Thrombolysis In Myocardial Infarction] major bleeding) were also evaluated at 7 days.Results: The primary efficacy outcome of cardiovascular death, MI, stroke, urgent revascularization or glycoprotein IIb/IIIa inhibitor bailout use did not differ between the quartiles of pre-treatment duration in the trial population (p = 0.17 for interaction). None of the secondary efficacy outcomes were found to be dependent on pre-treatment duration. The safety outcome of all CABG or non-CABG TIMI major bleeding did not differ between the quartiles of pre-treatment duration (p = 0.37 for interaction).Conclusions: In non-ST-segment elevation MI patients, the excess risk of bleeding and the absence of ischemic benefit were consistent across the quartiles of increasing duration of prasugrel pre-treatment. (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction [ACCOAST]; NCT01015287). [ABSTRACT FROM AUTHOR]

Background: The safety of the European Society of Cardiology (ESC) 0/1-h algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin (hs-cTn) has been questioned.Objectives: This study aimed to validate the diagnostic performance of the 0/1-h algorithm in a large multicenter study.Methods: The authors prospectively enrolled unselected patients in 6 countries presenting to the emergency department with symptoms suggestive of NSTEMI. Final diagnosis was centrally adjudicated by 2 independent cardiologists. Hs-cTnT and hs-cTnI blood concentrations were measured at presentation and after 1 h. Safety of rule-out was quantified by the negative predictive value (NPV) for NSTEMI, accuracy of rule-in by the positive predictive value (PPV), and overall efficacy by the proportion of patients triaged towards rule-out or rule-in within 1 h.Results: Prevalence of NSTEMI was 17%. Among 4,368 patients with serial hs-cTnT measurements available, safety of rule-out (NPV 99.8%, 2,488 of 2,493), accuracy of rule-in (PPV 74.5%, 572 of 768), and overall efficacy were high by assigning three-fourths of patients either to rule-out (57%, 2,493 to 4,368) or rule-in (18%, 768 to 4,368). Similarly, among 3,500 patients with serial hs-cTnI measurements, safety of rule-out (NPV 99.7%, 1,528 of 1,533), accuracy of rule-in (PPV 62.3%, 498 of 800), and overall efficacy were high by assigning more than two-thirds of patients either to rule-out (44%, 1,533 of 3,500) or rule-in (23%, 800 of 3,500). Excellent safety was confirmed in multiple subgroup analyses including patients presenting early (≤3 h) after chest pain onset.Conclusions: The ESC 0/1-h algorithm using hs-cTnT and hs-cTnI is very safe and effective in triaging patients with suspected NSTEMI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587; and Biomarkers in Acute Cardiac Care [BACC]; NCT02355457). [ABSTRACT FROM AUTHOR]

Background: When comparing effects of on- versus off-pump coronary artery bypass grafting (CABG), it is important to assess the long-term clinical outcomes. However, most research conducted thus far has concentrated on short-term outcomes and ignored the long-term clinical outcomes, especially the 5-year outcomes of the largest randomized controlled trials.Objectives: The aim of this systematic review and meta-analysis was to investigate the long-term clinical outcomes of on- versus off-pump CABG.Methods: To identify potential studies systematic searches were carried out using various databases. The search strategy included the key concepts of cardiopulmonary bypass AND off-pump AND long term OR 5-year outcomes. This was followed by a meta-analysis investigating mortality, incidence of myocardial infarction, incidence of angina, need for revascularization, and incidence of stroke.Results: Six studies totaling 8,145 participants were analyzed. In the on-pump group mortality was 12.3%, compared with 13.9% in the off-pump group. The odds ratio (OR) for this comparison was 1.16 (95% confidence interval [CI]: 1.02 to 1.32; p = 0.03; 13.9% vs. 12.3%). In contrast, there were no differences in the incidence of myocardial infarction (OR: 1.06: 95% CI: 0.91 to 1.25; p = 0.45; 8.4% vs. 7.9%), incidence of angina (OR: 1.09; 95% CI: 0.75 to 1.57; p = 0.65; 2.3% vs. 2.1%), need for revascularization (OR: 1.15; 95% CI: 0.95 to 1.40; p = 0.16; 5.9% vs. 5.1%), and the incidence of stroke (OR: 0.78; 95% CI: 0.56 to 1.10; p = 0.16; 2.2% vs. 2.8%).Conclusions: Statistically, on-pump CABG appeared to offer superior long-term survival, although the clinical significance of this may be more uncertain. [ABSTRACT FROM AUTHOR]

Background: Recent trials demonstrated a benefit of multivessel percutaneous coronary intervention (PCI) for noninfarct-related artery (non-IRA) stenosis over IRA-only PCI in patients with ST-segment elevation myocardial infarction (STEMI) multivessel disease. However, evidence is limited in patients with cardiogenic shock.Objectives: This study investigated the prognostic impact of multivessel PCI in patients with STEMI multivessel disease presenting with cardiogenic shock, using the nationwide, multicenter, prospective KAMIR-NIH (Korea Acute Myocardial Infarction-National Institutes of Health) registry.Methods: Among 13,104 consecutive patients enrolled in the KAMIR-NIH registry, we selected patients with STEMI with multivessel disease presenting with cardiogenic shock and who underwent primary PCI. Primary outcome was 1-year all-cause death, and secondary outcomes included patient-oriented composite outcome (a composite of all-cause death, any myocardial infarction, and any repeat revascularization) and its individual components.Results: A total of 659 patients were treated by multivessel PCI (n = 260) or IRA-only PCI (n = 399) strategy. The risk of all-cause death and non-IRA repeat revascularization was significantly lower in the multivessel PCI group than in the IRA-only PCI group (21.3% vs. 31.7%; hazard ratio: 0.59; 95% confidence interval: 0.43 to 0.82; p = 0.001; and 6.7% vs. 8.2%; hazard ratio: 0.39; 95% confidence interval: 0.17 to 0.90; p = 0.028, respectively). Results were consistent after multivariable regression, propensity-score matching, and inverse probability weighting to adjust for baseline differences. In a multivariable model, multivessel PCI was independently associated with reduced risk of 1-year all-cause death and patient-oriented composite outcome.Conclusions: Of patients with STEMI and multivessel disease with cardiogenic shock, multivessel PCI was associated with a significantly lower risk of all-cause death and non-IRA repeat revascularization. Our data suggest that multivessel PCI for complete revascularization is a reasonable strategy to improve outcomes in patients with STEMI with cardiogenic shock. [ABSTRACT FROM AUTHOR]

Background: Limited data are available on the relative performances between different types of drug-eluting stents (DES) for obstructive left main coronary artery disease (LMCAD).Objectives: This study sought to compare effectiveness and safety profiles of various second-generation DES for LMCAD in real-world clinical practice.Methods: Among 4,470 patients in 3, multicenter, prospective registries (IRIS-DES [Interventional Cardiology Research Incorporation Society-Drug-Eluting Stents] registry, the IRIS-MAIN [Interventional Cardiology Research Incorporation Society-Left MAIN Revascularization] registry, and the PRECOMBAT [PREmier of Randomized COMparison of Bypass Surgery versus AngioplasTy Using Drug-Eluting Stent in Patients with Left Main Coronary Artery Disease] study) treated between July 2007 and July 2015, the authors identified 2,692 patients with significant LMCAD who received second-generation DES; 1,254 with cobalt-chromium everolimus-eluting stents (CoCr-EES), 232 with biodegradable polymer biolimus-eluting stents (BP-BES), 616 with platinum-chromium EES (PtCr-EES), and 590 with Resolute zotarolimus-eluting stent (Re-ZES). The primary outcome was target-vessel failure.Results: The observed 3-year rates of target-vessel failure were not significantly different for the different types of DES (16.7% for the CoCr-EES, 13.2% for the BP-BES, 18.7% for the PtCr-EES, and 14.7% for the Re-ZES; p = 0.15). In multiple treatment propensity score analysis, the adjusted hazard ratios (HRs) for target-vessel failure were similar in between-group comparisons of the different DES, except for the PtCr-EES versus the BP-BES (reference; HR: 1.60; 95% confidence interval: 1.01 to 2.54; p = 0.046). There were no significant differences in risk of composite of all-cause death, any myocardial infarction, or any revascularization and its individual components according to the different types of DES. Although the 3-year incidence of stent thrombosis was considerably low (≤1.0%) for all types of DES, between-group differences were observed, generally favoring the EES platforms.Conclusions: In this pooled analysis of 3 prospective registries involving unrestricted use of various second-generation DES for LMCAD, we found no significant between-group differences in 3-year risk of target-vessel failure, except for a higher risk of primary outcome with PtCr-EES compared to BP-BES. (Evaluation of the First, Second, and New Drug-Eluting Stents in Routine Clinical Practice [IRIS-DES]; NCT01186133). [ABSTRACT FROM AUTHOR]

Background: Procedural technique may affect clinical outcomes after bioresorbable vascular scaffold (BVS) implantation. Prior studies suggesting such a relationship have not adjusted for baseline patient and lesion characteristics that may have influenced operator choice of technique and outcomes.Objectives: This study sought to determine whether target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) and scaffold thrombosis (ScT) rates within 3 years of BVS implantation are affected by operator technique (vessel size selection and pre- and post-dilation parameters).Methods: TLF and ScT rates were determined in 2,973 patients with 3,149 BVS-treated coronary artery lesions from 5 prospective studies (ABSORB II, ABSORB China, ABSORB Japan, ABSORB III, and ABSORB Extend). Outcomes through 3 years (and between 0 to 1 and 1 to 3 years) were assessed according to pre-specified definitions of optimal technique (pre-dilation, vessel sizing, and post-dilation). Multivariable analysis was used to adjust for differences in up to 18 patient and lesion characteristics.Results: Optimal pre-dilation (balloon to core laboratory-derived reference vessel diameter ratio ≥1:1), vessel size selection (reference vessel diameter ≥2.25 mm and ≤3.75 mm), and post-dilation (with a noncompliant balloon at ≥18 atm and larger than the nominal scaffold diameter, but not by >0.5 mm larger) in all BVS-treated lesions were performed in 59.2%, 81.6%, and 12.4% of patients, respectively. BVS implantation in properly sized vessels was an independent predictor of freedom from TLF through 1 year (hazard ratio [HR]: 0.67; p = 0.01) and through 3 years (HR: 0.72; p = 0.01), and of freedom from ScT through 1 year (HR: 0.36; p = 0.004). Aggressive pre-dilation was an independent predictor of freedom from ScT between 1 and 3 years (HR: 0.44; p = 0.03), and optimal post-dilation was an independent predictor of freedom from TLF between 1 and 3 years (HR: 0.55; p = 0.05).Conclusions: In the present large-scale analysis from the major ABSORB studies, after multivariable adjustment for baseline patient and lesion characteristics, vessel sizing and operator technique were strongly associated with BVS-related outcomes during 3-year follow-up. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281; ABSORB III Randomized Controlled Trial [RCT] [ABSORB-III]; NCT01751906; A Clinical Evaluation of Absorb Bioresorbable Vascular Scaffold [Absorb BVS] System in Chinese Population-ABSORB CHINA Randomized Controlled Trial [RCT] [ABSORB CHINA]; NCT01923740; ABSORB EXTEND Clinical Investigation [ABSORB EXTEND]; NCT01023789; AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284). [ABSTRACT FROM AUTHOR]

Background: Provisional stenting (PS) is the most common technique used to treat distal left main (LM) bifurcation lesions in patients with unprotected LM coronary artery disease undergoing percutaneous coronary intervention. The double kissing (DK) crush planned 2-stent technique has been shown to improve clinical outcomes in non-LM bifurcations compared with PS, and in LM bifurcations compared with culotte stenting, but has never been compared with PS in LM bifurcation lesions.Objectives: The authors sought to determine whether a planned DK crush 2-stent technique is superior to PS for patients with true distal LM bifurcation lesions.Methods: The authors randomized 482 patients from 26 centers in 5 countries with true distal LM bifurcation lesions (Medina 1,1,1 or 0,1,1) to PS (n = 242) or DK crush stenting (n = 240). The primary endpoint was the 1-year composite rate of target lesion failure (TLF): cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Routine 13-month angiographic follow-up was scheduled after ascertainment of the primary endpoint.Results: TLF within 1 year occurred in 26 patients (10.7%) assigned to PS, and in 12 patients (5.0%) assigned to DK crush (hazard ratio: 0.42; 95% confidence interval: 0.21 to 0.85; p = 0.02). Compared with PS, DK crush also resulted in lower rates of target vessel myocardial infarction I (2.9% vs. 0.4%; p = 0.03) and definite or probable stent thrombosis (3.3% vs. 0.4%; p = 0.02). Clinically driven target lesion revascularization (7.9% vs. 3.8%; p = 0.06) and angiographic restenosis within the LM complex (14.6% vs. 7.1%; p = 0.10) also tended to be less frequent with DK crush compared with PS. There was no significant difference in cardiac death between the groups.Conclusions: In the present multicenter randomized trial, percutaneous coronary intervention of true distal LM bifurcation lesions using a planned DK crush 2-stent strategy resulted in a lower rate of TLF at 1 year than a PS strategy. (Double Kissing and Double Crush Versus Provisional T Stenting Technique for the Treatment of Unprotected Distal Left Main True Bifurcation Lesions: A Randomized, International, Multi-Center Clinical Trial [DKCRUSH-V]; ChiCTR-TRC-11001213). [ABSTRACT FROM AUTHOR]

Background: Subjects undergoing coronary stenting with complex lesion anatomy may experience different risks and benefits with prolonged dual antiplatelet therapy.Objectives: The authors assessed the effect of 30 months versus 12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) based on the presence or absence of anatomically-complex target lesions.Methods: In the DAPT Study, combined myocardial infarction (MI) or stent thrombosis and moderate/severe bleeding were assessed in enrolled (n = 25,416) and randomized (n = 11,554) subjects. Complex lesions had any of the following characteristics: unprotected left main, >2 lesions/vessel, length ≥30 mm, bifurcation with side branch ≥2.5 mm, vein bypass graft, or thrombus-containing lesion. Events were evaluated according to increasing number of complexity characteristics and compared according to DAPT score.Results: Enrolled subjects with more complex target lesions had higher rates of MI or stent thrombosis in the first 12 months after PCI (3.9% vs. 2.4%; p < 0.001). Among those who were event-free at 12 months, rates of MI or stent thrombosis between 12 and 30 months were similar between those with versus without complex anatomy (3.5% vs. 2.9%; p = 0.07). Reduction of MI or stent thrombosis with continued thienopyridine beyond 12 months versus placebo was similar for subjects with (2.5% vs. 4.5%; hazard ratio: 0.55; 95% confidence interval: 0.38 to 0.79; p = 0.001) and without (2.0% vs. 3.8%; hazard ratio: 0.52; 95% confidence interval: 0.39 to 0.69; p < 0.001) anatomic complexity (pinteraction = 0.81), as was increase in moderate/severe bleeding (pinteraction = 0.44). Among subjects with anatomic complexity, those with DAPT scores ≥2 randomized to continued thienopyridine had greater reductions in MI or stent thrombosis (3.0% vs. 6.1%; p < 0.001) compared with subjects with scores <2 (1.7% vs. 2.3%; p = 0.42; p value comparing risk differences = 0.03).Conclusions: Complex target-lesion anatomy is associated with increased ischemic events, particularly within the first year after PCI. Among those without events in the first 12 months, the benefits of extending DAPT were similar in subjects with and without complex lesions. A high DAPT score identified those experiencing the most benefit from extended treatment among patients with and without complex anatomy. (The Dual Antiplatelet Therapy Study [DAPT Study]; NCT00977938). [ABSTRACT FROM AUTHOR]

Background: Uncertainties regarding the most appropriate definition and treatment of type 2 myocardial infarction (T2MI) due to supply-demand mismatch have contributed to inconsistent adoption in clinical practice.Objectives: This study sought a better understanding of the effect of the definition of T2MI on its incidence, treatment, and event-related mortality, thereby addressing an important unmet clinical need.Methods: The final diagnosis was adjudicated in patients presenting with symptoms suggestive of myocardial infarction by 2 independent cardiologists by 2 methods: 1 method required the presence of coronary artery disease, a common interpretation of the 2007 universal definition (T2MI2007); and 1 method did not require coronary artery disease, the 2012 universal definition (T2MI2012).Results: Overall, 4,015 consecutive patients were adjudicated. The incidence of T2MI based on the T2MI2007 definition was 2.8% (n = 112). The application of the more liberal T2MI2012 definition resulted in an increase of T2MI incidence of 6% (n = 240), a relative increase of 114% (128 reclassified patients, defined as T2MI2012reclassified). Among T2MI2007, 6.3% of patients received coronary revascularization, 22% dual-antiplatelet therapy, and 71% high-dose statin therapy versus 0.8%, 1.6%, and 31% among T2MI2012reclassified patients, respectively (all p < 0.01). Cardiovascular mortality at 90 days was 0% among T2MI2012reclassified, which was similar to patients with noncardiac causes of chest discomfort (0.2%), and lower than T2MI2007 (3.6%) and type 1 myocardial infarction (T1MI) (4.8%) (T2MI2012reclassified vs. T2MI2007 and T1MI: p = 0.03 and 0.01, respectively).Conclusions: T2MI2012reclassified has a substantially lower event-related mortality rate compared with T2MI2007 and T1MI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587). [ABSTRACT FROM AUTHOR]

Background: Severity of left atrial (LA) fibrosis is a strong predictor of atrial fibrillation (AF) ablation success and has been associated with a history of stroke, hypertension, and heart failure (HF). However, it is unclear whether more severe LA fibrosis independently increases the risk of major adverse cardiovascular and cerebrovascular events (MACCE) among those with AF.Objectives: The goal of this study was to evaluate the occurrence and frequency of MACCE by strata of LA fibrosis severity in patients with AF.Methods: This was a retrospective cohort study of 1,228 patients with AF who underwent late gadolinium enhancement (LGE)-cardiac magnetic resonance imaging to quantify LA fibrosis severity between January 2007 and June 2015. Patients were stratified according to Utah stage of LA LGE criteria, and observed for the occurrence of MACCE, which included a composite of stroke or transient ischemic attack (TIA), myocardial infarction, acute decompensated HF, or cardiovascular death. Disease risk score (DRS) stratification was used to control for between-group differences in baseline characteristics and risk.Results: During follow-up, 62 strokes or TIAs, 42 myocardial infarctions, 156 HF events, and 38 cardiovascular deaths occurred. In DRS stratified analysis, the hazard ratio comparing patients with stage IV versus stage I LA LGE was 1.67 (95% confidence interval: 1.01 to 2.76) for the composite MACCE outcome. The only individual component of the MACCE outcome to remain significantly associated with advanced LGE following DRS stratification was stroke or TIA (hazard ratio: 3.94; 95% confidence interval: 1.72 to 8.98).Conclusions: This retrospective analysis demonstrated that more severe LA LGE is associated with increased MACCE risk, driven primarily by increased risk of stroke or TIA. [ABSTRACT FROM AUTHOR]

Background: Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time.Objectives: The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization.Methods: The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3).Results: A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65).Conclusions: Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562). [ABSTRACT FROM AUTHOR]

Background: The risk of arterial thromboembolism in patients with cancer is incompletely understood.Objectives: The authors aimed to better define this epidemiological relationship, including the effects of cancer stage.Methods: Using the Surveillance Epidemiology and End Results-Medicare linked database, the authors identified patients with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, pancreatic, or gastric cancer or non-Hodgkin lymphoma from 2002 to 2011. They were individually matched by demographics and comorbidities to a Medicare enrollee without cancer, and each pair was followed through 2012. Validated diagnosis codes were used to identify arterial thromboembolism, defined as myocardial infarction or ischemic stroke. Cumulative incidence rates were calculated using competing risk survival statistics. Cox hazards analysis was used to compare rates between groups at discrete time points.Results: The authors identified 279,719 pairs of patients with cancer and matched control patients. The 6-month cumulative incidence of arterial thromboembolism was 4.7% (95% confidence interval [CI]: 4.6% to 4.8%) in patients with cancer compared with 2.2% (95% CI: 2.1% to 2.2%) in control patients (hazard ratio [HR]: 2.2; 95% CI: 2.1 to 2.3). The 6-month cumulative incidence of myocardial infarction was 2.0% (95% CI: 1.9% to 2.0%) in patients with cancer compared with 0.7% (95% CI: 0.6% to 0.7%) in control patients (HR: 2.9; 95% CI: 2.8 to 3.1). The 6-month cumulative incidence of ischemic stroke was 3.0% (95% CI: 2.9% to 3.1%) in patients with cancer compared with 1.6% (95% CI: 1.6% to 1.7%) in control patients (HR: 1.9; 95% CI: 1.8 to 2.0). Excess risk varied by cancer type (greatest for lung), correlated with cancer stage, and generally had resolved by 1 year.Conclusions: Patients with incident cancer face a substantially increased short-term risk of arterial thromboembolism. [ABSTRACT FROM AUTHOR]

Background: In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding.Objectives: The authors evaluated cost-effectiveness of ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years.Methods: The authors performed a prospective economic substudy alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162 patients to ASA alone, ticagrelor 60 mg twice daily + low-dose ASA, or ticagrelor 90 mg twice daily + low-dose ASA. Medical resource use data were collected over a median 33-month follow-up. Costs were assessed from the U.S. health care system perspective. In-trial data relating to survival, utility, and costs were combined with lifetime projections to evaluate lifetime cost-effectiveness of the Food and Drug Administration-approved lower-dose ticagrelor regimen (60 mg twice daily).Results: Hospitalization costs were similar for ticagrelor 60 mg and placebo ($2,262 vs. $2,333; 95% confidence interval for difference -$303 to $163; p = 0.54); after inclusion of a daily ticagrelor 60 mg cost of $10.52, total costs were higher for ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p < 0.001). In-trial quality-adjusted life-years (QALYs) were similar (2.28 vs. 2.27; p = 0.34). Over a lifetime horizon, ticagrelor was associated with QALY gains of 0.078 and incremental costs of $7,435, yielding an incremental cost-effectiveness ratio (ICER) of $94,917/QALY gained. Several high-risk groups had more favorable ICERs, including patients with >1 prior MI, multivessel disease, diabetes, renal dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age <75 years (ICER = $44,779/QALY gained), and patients with peripheral artery disease (ICER = $13,427/QALY gained).Conclusions: For patients with a history of MI >1 year previously, long-term treatment with ticagrelor 60 mg + low-dose ASA yields a cost-effectiveness ratio suggesting intermediate value based on current guidelines. Ticagrelor appears to provide higher value for patients in several recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562). [ABSTRACT FROM AUTHOR]

Background: Spontaneous coronary artery dissection (SCAD) is the most common cause of pregnancy-associated myocardial infarction and remains poorly characterized.Objectives: This study sought to assess presentation, clinical factors, and outcomes of pregnancy-associated spontaneous coronary artery dissection (P-SCAD) compared with spontaneous coronary artery dissection not associated with pregnancy (NP-SCAD).Methods: A Mayo Clinic registry was established in 2010 to include comprehensive retrospective and prospective SCAD data. Records were reviewed to identify women who were pregnant or ≤12 weeks postpartum at time of SCAD. Complete records were available for 323 women; 54 women met criteria for P-SCAD (4 during pregnancy) and they were compared with 269 women with NP-SCAD.Results: Most events occurred within the first month postpartum (35 of 50). Compared with NP-SCAD, P-SCAD patients more frequently presented with ST-segment elevation myocardial infarction (57% vs. 36%; p = 0.009), left main or multivessel SCAD (24% vs. 5%; p < 0.0001; and 33% vs. 14%; p = 0.0027, respectively), and left ventricular function ≤35% (26% vs. 10%; p = 0.0071). Among women with imaging of other vascular territories, P-SCAD was less likely with a diagnosis of fibromuscular dysplasia and extracoronary vascular abnormalities (42% vs. 64%; p = 0.047; and 46% vs. 77%; p = 0.0032, respectively). Compared with U.S. birth data, women with P-SCAD were more often multiparous (p = 0.0167), had a history of infertility therapies (p = 0.0004), and had pre-eclampsia (p = 0.001). On long-term follow-up (median 2.3 years) recurrent SCAD occurred in 51 patients, with no difference in the Kaplan Meier 5-year recurrence rates (10% vs. 23%; p = 0.18).Conclusions: P-SCAD patients had more acute presentations and high-risk features than women with NP-SCAD did. The highest frequency of P-SCAD occurred during the first postpartum month and P-SCAD patients less often had extracoronary vascular abnormalities. Hormonal, hemodynamic variations, and yet-undefined mechanisms might be significant contributors to P-SCAD. (The "Virtual" Multicenter Spontaneous Coronary Artery Dissection [SCAD] Registry [SCAD]; NCT01429727; Genetic Investigations in Spontaneous Coronary Artery Dissection [SCAD]; NCT01427179). [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) have increased risk of thromboembolic events such as stroke and myocardial infarction (MI). Although it has been established that the efficacy of anticoagulation is superior to that of antiplatelet agents for stroke prophylaxis in AF, the optimal antithrombotic treatment remains uncertain for primary protection against MI.Objectives: The authors investigated the incidence of first-time MI in patients with AF according to antithrombotic treatment and estimated the risk of stroke and bleeding.Methods: Subjects with first-time AF diagnosed from 1997 to 2012 without history of coronary artery disease were identified using Danish nationwide administrative registries. Subjects were divided into time varying exposure groups according to antithrombotic treatment. The relative risks of outcomes were estimated by Poisson regression models.Results: A total of 71,959 patients (median 75 years of age; females: 47%). At baseline, 37,539 patients (52%) were treated with vitamin K antagonist (VKA) monotherapy, 25,458 (35%) with acetylsalicylic acid (ASA) monotherapy and 8,962 (13%) with dual-therapy (VKA + ASA). The incidence of MI was 3% (n = 2,275). Relative to the VKA-treated group, the associated risk of MI was significantly higher for ASA (incidence rate ratio [IRR]: 1.54; 95% confidence interval [CI]: 1.40 to 1.68) and dual-therapy (IRR: 1.22; 95% CI: 1.06 to 1.40). The bleeding risk was significantly higher for dual-therapy (IRR: 1.93; 95% CI: 1.81 to 2.07). The risk of stroke relative to that of VKA therapy was significantly higher for both ASA (IRR: 2.00; 95% CI: 1.88 to 2.12) and dual-therapy (IRR: 1.30; 95% CI: 1.18 to 1.43).Conclusions: VKA monotherapy in patients with AF was associated with a lower risk of first-time MI and stroke than ASA monotherapy. Combination of ASA and VKA therapy was not associated with a lower risk of MI but was associated with increased bleeding risk. [ABSTRACT FROM AUTHOR]

Background: For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality.Objectives: The goal of this study was to determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD).Methods: This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality.Results: Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non-ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: -0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: -0.98 to 1.58; p = 0.637) and non-ST-segment elevation myocardial infarction (ATE coefficient: -0.07; 95% CI: -0.68 to 0.54; p = 0.819).Conclusions: Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654). [ABSTRACT FROM AUTHOR]

Background: Lipid-rich plaque (LRP) is thought to be a precursor to cardiac events. However, its clinical significance in coronary arteries has never been systematically investigated.Objectives: This study investigated the prevalence and clinical significance of LRP in the nonculprit region of the target vessel in patients undergoing percutaneous coronary intervention (PCI).Methods: The study included 1,474 patients from 20 sites across 6 countries undergoing PCI, who had optical coherence tomography (OCT) imaging of the target vessel. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, acute myocardial infarction, and ischemia-driven revascularization. Patients were followed for up to 4 years (median of 2 years).Results: Lipid-rich plaque was detected in nonculprit regions of the target vessel in 33.6% of patients. The cumulative rate of nonculprit lesion-related MACE (NC-MACE) over 48 months in patients with LRP was higher than in those without LRP (7.2% vs. 2.6%, respectively; p = 0.033). Acute coronary syndrome at index presentation (risk ratio: 2.538; 95% confidence interval [CI]: 1.246 to 5.173; p = 0.010), interruption of statin use ≥1 year (risk ratio: 4.517; 95% CI: 1.923 to 10.610; p = 0.001), and LRP in nonculprit regions (risk ratio: 2.061; 95% CI: 1.050 to 4.044; p = 0.036) were independently associated with increased NC-MACE. Optical coherence tomography findings revealed that LRP in patients with NC-MACE had longer lipid lengths (p < 0.001), wider maximal lipid arcs (p = 0.023), and smaller minimal lumen areas (p = 0.003) than LRPs in patients without MACE.Conclusions: Presence of LRP in the nonculprit regions of the target vessel by OCT predicts increased risk for future NC-MACE, which is primarily driven by revascularization for recurrent ischemia. Lipid-rich plaque with longer lipid length, wider lipid arc, and higher degree of stenosis identified patients at higher risk of future cardiac events. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538). [ABSTRACT FROM AUTHOR]

Background: The ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes) trial compared early invasive strategy with a selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and an elevated cardiac troponin T. No long-term benefit of an early invasive strategy was found at 1 and 5 years.Objectives: The aim of this study was to determine the 10-year clinical outcomes of an early invasive strategy versus a selective invasive strategy in patients with NSTE-ACS and an elevated cardiac troponin T.Methods: The ICTUS trial was a multicenter, randomized controlled clinical trial that included 1,200 patients with NSTE-ACS and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003. We collected 10-year follow-up of death, myocardial infarction (MI), and revascularization through the Dutch population registry, patient phone calls, general practitioners, and hospital records. The primary outcome was the 10-year composite of death or spontaneous MI. Additional outcomes included the composite of death or MI, death, MI (spontaneous and procedure-related), and revascularization.Results: Ten-year death or spontaneous MI was not statistically different between the 2 groups (33.8% vs. 29.0%, hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.97 to 1.46; p = 0.11). Revascularization occurred in 82.6% of the early invasive group and 60.5% in the selective invasive group. There were no differences in additional outcomes, except for a higher rate of death or MI in the early invasive group compared with the rates for the selective invasive group (37.6% vs. 30.5%; HR: 1.30; 95% CI: 1.07 to 1.58; p = 0.009), driven by a higher rate of procedure-related MI in the early invasive group (6.5% vs. 2.4%; HR: 2.82; 95% CI: 1.53 to 5.20; p = 0.001).Conclusions: In patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive strategy has no benefit over a selective invasive strategy in reducing the 10-year composite outcome of death or spontaneous MI, and a selective invasive strategy may be a viable option in selected patients. [ABSTRACT FROM AUTHOR]

Background: First-generation drug-eluting coronary stents (DES) were introduced in 2003 to 2004, and their use resulted in a considerable reduction in the development of in-stent restenosis at the cost of an increased risk of late stent thromboses.Objectives: This study followed clinical outcomes of patients included in a large randomized trial for 10 years to enable detection of late changes in annual event rates that could necessitate medical attention.Methods: A total of 2,098 unselected all-comer patients (50% with acute coronary syndrome) were randomly assigned to have a first-generation DES implanted. This study recorded the occurrence of a major adverse cardiac event (MACE) assessed as the composite of cardiac death, myocardial infarction, and target vessel revascularization. Stent thromboses were also assessed.Results: Of the 2,098 unselected patients, 73.1% were still alive after 10 years. During the follow-up period, MACE occurred in 346 (32.5%) in the group receiving a sirolimus-eluting stent and in 342 (33.1%) in the group receiving a paclitaxel-eluting stent (hazard ratio: 0.96; 95% confidence interval: 0.83 to 1.11; p = 0.60), with a steady annual rate of 2.6% after the first year. Definite, probable, and possible stent thrombosis appeared in 279 patients (13.3%), with no difference between stent types and with a steady annual rate of 1.3% after the first year.Conclusions: Among the surviving patients, the long-term annual MACE rate and the stent thrombosis rate appeared constant for both stent types, with no apparent late changes. Although there is no need for extraordinary medical attention for these patients, the absence of declines in annual event rates calls for continuous surveillance. (Danish Organization on Randomized Trials With Clinical Outcome II [SORT OUT II]; NCT00388934). [ABSTRACT FROM AUTHOR]

Background: A 1-year follow-up, polymer-free metallic stent coated with biolimus-A9 followed by 1-month dual antiplatelet therapy is safer and more effective than a bare-metal stent (BMS) for patients with high risk of bleeding.Objectives: This study analyzed 2-year outcomes to determine whether these benefits are maintained.Methods: In a prospective, multicenter, double-blind trial, we randomized 2,466 high bleeding risk patients to receive a drug-coated stent (DCS) or a BMS followed by 1-month dual antiplatelet therapy. The primary safety endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy endpoint was clinically driven target lesion revascularization.Results: At 2 years, the primary safety endpoint had occurred in 147 DCS and 180 BMS patients (15.3%) (hazard ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.039). Clinically driven target lesion revascularization occurred for 77 DCS and 136 BMS patients (12.0%) (hazard ratio: 0.54; 95% confidence interval: 0.41 to 0.72; p < 0.0001). Major bleeding occurred in 8.9% of DCS and 9.2% of BMS patients (p = 0.95), and a coronary thrombotic event (myocardial infarction and/or stent thrombosis) occurred in 8.2% of DCS and 10.6% of BMS patients (p = 0.045). One-year mortality was 27.1% for a major bleed and 26.3% for a thrombotic event. At 2 years, multivariate correlates of major bleeding were age >75 years, anemia, raised plasma creatinine, and planned long-term anticoagulation. Correlates of the primary safety endpoint were age, anemia, congestive heart failure, multivessel disease, number of stents implanted, and use of a BMS rather than a DCS.Conclusions: Safety and efficacy benefits of DCS over BMS were maintained for 2 years in high bleeding risk patients. Rates of major bleeding and coronary thrombotic events were no different and were associated with a substantial and comparable mortality risk. (A Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug Coated Stent Versus the Gazelle Bare Metal Stent in Patients With High Risk of Bleeding [LEADERS FREE]; NCT01623180). [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines recommend post-operative dual antiplatelet therapy (DAPT) in patients who undergo coronary artery bypass grafting (CABG) following acute coronary syndromes (ACS).Objectives: The authors have evaluated DAPT utilization rates and associated outcomes among post-CABG patients with diabetes.Methods: In a post hoc, nonrandomized analysis from the FREEDOM (Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease) trial, we compared patients receiving DAPT (aspirin plus thienopyridine) and aspirin monotherapy at 30 days post-operatively. The primary outcome was the risk adjusted 5-year FREEDOM composite of all-cause mortality, nonfatal myocardial infarction, or stroke. Safety outcomes included major bleeding, blood transfusion, and hospitalization for bleeding.Results: At 30 days post-CABG, 544 (68.4%) patients received DAPT and 251 (31.6%) patients received aspirin alone. The median (25th, 75th percentile) duration of clopidogrel therapy was 0.98 (0.23 to 1.91) years. There was no significant difference in the 5-year primary composite outcome between DAPT- and aspirin-treated patients (12.6% vs. 16.0%; adjusted hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.54 to 1.27; p = 0.39). The 5-year primary composite outcomes were similar for patients receiving DAPT versus aspirin monotherapy respectively, in subgroups with pre-CABG ACSs (15.2% vs. 16.5%; HR: 1.06; 95% CI: 0.53 to 2.10; p = 0.88) and those with stable angina (11.6% vs. 15.8%; HR: 0.82; 95% CI: 0.50 to 1.343; p = 0.42). The composite outcomes of both treatment groups were also similar by SYNTAX score, duration of DAPT therapy, completeness of revascularization, and in off-pump CABG. No treatment-related differences in major bleeding (5.6% vs. 5.7%; HR: 1.00; 95% CI: 0.50 to 1.99; p = 0.99), blood transfusions (4.8% vs. 4.5%; HR: 1.09; 95% CI: 0.51 to 2.34; p = 0.82), or hospitalization for bleeding (2.6% vs. 3.3%; HR: 0.85; 95% CI: 0.34 to 2.17; p = 0.74) were observed between aspirin- and DAPT-treated patients, respectively.Conclusions: The use of DAPT in patients with diabetes post-CABG in our cohort was high. Compared with aspirin monotherapy, no associated differences were observed in cardiovascular or bleeding outcomes, suggesting that routine use of DAPT may not be clinically warranted. (Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease [FREEDOM]; NCT00086450). [ABSTRACT FROM AUTHOR]

Background: Understanding the relationship between alcohol abuse, a common and theoretically modifiable condition, and the most common cause of death in the world, cardiovascular disease, may inform potential prevention strategies.Objectives: The study sought to investigate the associations among alcohol abuse and atrial fibrillation (AF), myocardial infarction (MI), and congestive heart failure (CHF).Methods: Using the Healthcare Cost and Utilization Project database, we performed a longitudinal analysis of California residents ≥21 years of age who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2009. We determined the risk of an alcohol abuse diagnosis on incident AF, MI, and CHF. Patient characteristics modifying the associations and population-attributable risks were determined.Results: Among 14,727,591 patients, 268,084 (1.8%) had alcohol abuse. After multivariable adjustment, alcohol abuse was associated with an increased risk of incident AF (hazard ratio [HR]: 2.14; 95% confidence interval [CI]: 2.08 to 2.19; p < 0.0001), MI (HR: 1.45; 95% CI: 1.40 to 1.51; p < 0.0001), and CHF (HR: 2.34; 95% CI: 2.29 to 2.39; p < 0.0001). In interaction analyses, individuals without conventional risk factors for cardiovascular disease exhibited a disproportionately enhanced risk of each outcome. The population-attributable risk of alcohol abuse on each outcome was of similar magnitude to other well-recognized modifiable risk factors.Conclusions: Alcohol abuse increased the risk of AF, MI, and CHF to a similar degree as other well-established risk factors. Those without traditional cardiovascular risk factors are disproportionately prone to these cardiac diseases in the setting of alcohol abuse. Thus, efforts to mitigate alcohol abuse might result in meaningful reductions of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend primary prevention with statins for individuals with ≥7.5% 10-year risk for atherosclerotic cardiovascular disease (ASCVD). Everyone living long enough will become eligible for risk-based statin therapy due to age alone.Objectives: This study sought to personalize ACC/AHA risk-based statin eligibility using noninvasive assessment of subclinical atherosclerosis.Methods: In 5,805 BioImage participants without known ASCVD at baseline, those with ≥7.5% 10-year ASCVD risk were down-classified from statin eligible to ineligible if imaging revealed no coronary artery calcium (CAC) or carotid plaque burden (cPB). Intermediate-risk individuals were up-classified from optional to clear statin eligibility if CAC was ≥100 (or equivalent cPB).Results: At a median follow-up of 2.7 years, 91 patients had coronary heart disease and 138 had experienced a cardiovascular disease event. Mean age of the participants was 69 years, and 86% qualified for ACC/AHA risk-based statin therapy, with high sensitivity (96%) but low specificity (15%). CAC or cPB scores of 0 were common (32% and 23%, respectively) and were associated with low event rates. With CAC-guided reclassification, specificity for coronary heart disease events improved 22% (p < 0.0001) without any significant loss in sensitivity, yielding a binary net reclassification index (NRI) of 0.20 (p < 0.0001). With cPB-guided reclassification, specificity improved 16% (p < 0.0001) with a minor loss in sensitivity (7%), yielding an NRI of 0.09 (p = 0.001). For cardiovascular disease events, the NRI was 0.14 (CAC-guided) and 0.06 (cPB-guided). The positive NRIs were driven primarily by down-classifying the large subpopulation with CAC = 0 or cPB = 0.Conclusions: Withholding statins in individuals without CAC or carotid plaque could spare a significant proportion of elderly people from taking a pill that would benefit only a few. This individualized disease-guided approach is simple and easy to implement in routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: Although guideline-recommended therapies reduce major adverse cardiovascular events (MACE) in patients after myocardial infarction (MI) or those with atherosclerotic disease (ATH), adherence is poor.Objectives: The goal of this study was to determine the association between medication adherence levels and long-term MACE in these patients.Methods: We queried the claims database of a large health insurer for patients hospitalized for MI or with ATH. The primary outcome measure was a composite of all-cause death, MI, stroke, or coronary revascularization. Using proportion of days covered for statins and angiotensin-converting enzyme inhibitors, patients were stratified as fully adherent (≥80%), partially adherent (≥40% to ≤79%), or nonadherent (<40%). Per-patient annual direct medical (ADM) costs were estimated by using unit costs from 2 national files.Results: Data were analyzed for 4,015 post-MI patients and 12,976 patients with ATH. In the post-MI cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (18.9% vs. 26.3%; hazard ratio [HR]: 0.73; p = 0.0004) and partially adherent (18.9% vs. 24.7%; HR: 0.81; p = 0.02) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $369 and $440 compared with the partially adherent and nonadherent groups, respectively. In the ATH cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (8.42% vs. 17.17%; HR: 0.56; p < 0.0001) and the partially adherent (8.42% vs. 12.18%; HR: 0.76; p < 0.0001) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $371 and $907 compared with the partially adherent and nonadherent groups.Conclusions: Full adherence to guideline-recommended therapies was associated with a lower rate of MACE and cost savings, with a threshold effect at >80% adherence in the post-MI population; at least a 40% level of long-term adherence needs to be maintained to continue to accrue benefit. Novel approaches to improve adherence may significantly reduce cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Bioabsorbable cardiac matrix (BCM) is a novel device that attenuates adverse left ventricular (LV) remodeling after large myocardial infarctions in experimental models.Objectives: This study aimed to analyze whether BCM, compared with saline control, would result in less LV dilation and fewer adverse clinical events between baseline and 6 months.Methods: In an international, randomized, double-blind, controlled trial, 303 subjects with large areas of infarction despite successful primary percutaneous coronary intervention (PCI) of ST-segment elevation myocardial infarction (STEMI) were randomized 2:1 to BCM or saline injected into the infarct-related artery 2 to 5 days after primary PCI. The primary outcome was mean change from baseline in LV end-diastolic volume index (LVEDVI) at 6 months. Secondary outcomes included change in Kansas City Cardiomyopathy Questionnaire score, 6-minute walk time, and New York Heart Association functional class at 6 months. The primary safety endpoint was a composite of cardiovascular death, recurrent MI, target-vessel revascularization, stent thrombosis, significant arrhythmia requiring therapy, or myocardial rupture through 6 months.Results: In total, 201 subjects were assigned to BCM and 102 to saline control. There was no significant difference in change in LVEDVI from baseline to 6 months between the groups (mean change ± SD: BCM 14.1 ± 28.9 ml/m(2) vs. saline 11.7 ± 26.9 ml/m(2); p = 0.49). There was also no significant difference in the secondary endpoints. The rates of the primary safety outcome were similar between the 2 groups (BCM 11.6% vs. saline 9.1%; p = 0.37).Conclusions: Intracoronary deployment of BCM 2 to 5 days after successful reperfusion in subjects with large myocardial infarction did not reduce adverse LV remodeling or cardiac clinical events at 6 months. (IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction [PRESERVATION I]; NCT01226563). [ABSTRACT FROM AUTHOR]

Background: Diabetic patients are at increased risk for future cardiovascular events after ST-segment elevation myocardial infarction (STEMI). Administration of an intracoronary abciximab bolus during primary percutaneous coronary intervention (PCI) may be beneficial in this high-risk subgroup.Objectives: This study sought to report the 1-year clinical outcomes and cardiac magnetic resonance (CMR) findings in STEMI patients with and without diabetes randomized to intracoronary or intravenous abciximab bolus at the time of primary PCI.Methods: Patient-level data from 3 randomized trials were pooled. The primary endpoint was the composite of death or reinfarction. Comprehensive CMR imaging was performed in 1 study.Results: Of 2,470 patients, 473 (19%) had diabetes and 1,997 (81%) did not. At 1 year, the primary endpoint was significantly reduced in diabetic patients randomized to intracoronary abciximab compared with those randomized to intravenous bolus (9.2% vs. 17.6%; hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.83; p = 0.009). The intracoronary abciximab bolus did not reduce the primary endpoint in patients without diabetes (7.4% vs. 7.5%; HR: 0.95; 95% CI: 0.68 to 1.33; p = 0.77), resulting in a significant interaction (p = 0.034). Among diabetic patients, intracoronary versus intravenous abciximab bolus was associated with a significantly reduced risk of death (5.8% vs. 11.2%; HR: 0.51; 95% CI: 0.26 to 0.98; p = 0.043) and definite/probable stent thrombosis (1.3% vs. 4.8%; HR: 0.27; 95% CI: 0.08 to 0.98; p = 0.046). At CMR (n = 792), the myocardial salvage index was significantly increased only in diabetic patients randomized to intracoronary compared with intravenous abciximab (54.4; interquartile range: 35.1 to 78.2 vs. 39.0, interquartile range: 24.7 to 61.7; p = 0.011; p for interaction vs. no diabetes = 0.016).Conclusions: In diabetic patients with STEMI, the administration of intracoronary abciximab improved the effectiveness of primary PCI compared with the intravenous bolus. [ABSTRACT FROM AUTHOR]