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• COMPETENCY IN MEDICAL KNOWLEDGE: This prospectively planned secondary analysis of the VICTORIA study preselected 5 biomarkers measured at baseline and 16 weeks thought to reflect the potentially beneficial nonvasodilatory mechanisms of action of vericiguat, a sGC stimulator, in patients with heart failure with a reduced ejection fraction. • COMPETENCY IN PATIENT CARE: In this population with a high event rate, baseline hs-cTnT, GDF-15, and IL-6 were prognostic in a comprehensive adjustment model inclusive of NT-proBNP levels. • TRANSLATIONAL OUTLOOK: This study is one of the first to identify that progressively lower baseline levels of hs-cTnT could distinguish participants deriving increasing benefit from a specific heart failure treatment to decrease cardiovascular death. Circulating biomarkers may be useful in understanding prognosis and treatment efficacy in heart failure with reduced ejection fraction. In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, vericiguat, a soluble guanylate cyclase stimulator, decreased the primary outcome of cardiovascular death or heart failure hospitalization in heart failure with reduced ejection fraction. We evaluated biomarkers of cardiac injury, inflammation, and renal function for associations with outcomes and vericiguat treatment effect. High-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and cystatin C were measured at baseline and 16 weeks. Associations of biomarkers with the primary outcome and its components were estimated. Interaction with study treatment was tested. Changes in biomarkers over time were examined by study treatment. One or more biomarkers were measured in 4652 (92%) of 5050 participants at baseline and 4063 (81%) at 16 weeks. After adjustment, higher values of hs-cTnT, growth differentiation factor-15, and interleukin-6 were associated with the primary outcome, independent of N-terminal pro-B-type natriuretic peptide. Higher hs-cTnT values were associated with a hazard ratio per log standard deviation of 1.21 (95% confidence interval 1.14–1.27). A treatment interaction with vericiguat was evident with hs-cTnT and cardiovascular death (P =.04), but not HF hospitalization (P =.38). All biomarkers except cystatin C decreased over 16 weeks and no relationship between treatment assignment and changes in biomarker levels was observed. hs-cTnT, growth differentiation factor-15, and interleukin-6 levels were associated with risk of the primary outcome in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). Uniquely, lower hs-cTnT was associated with a lower rate of cardiovascular death but not HF hospitalization after treatment with vericiguat. [Display omitted] [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2010.02.028 Byline: Osama Alhadramy (a), Cynthia M. Westerhout (a), Sorin J. Brener (b), Christopher B. Granger (c), Paul W. Armstrong (a) Abstract: Accurate estimation of coronary epicardial flow in patients with ST-elevation myocardial infarction (STEMI) is crucial to evaluating the effect of therapy and predicting outcome. Whether operator bias exists in visual estimation of TIMI flow grade among patients with STEMI undergoing primary percutaneous coronary intervention (PCI) remains uncertain. Hence, we examined this issue in the angiographic substudy of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. Author Affiliation: (a) University of Alberta, Edmonton Alberta, Canada (b) New York Methodist Hospital, Brooklyn NY (c) Duke Clinical Research Institute, Durham NC Article History: Received 10 November 2009; Accepted 24 February 2010 Article Note: (footnote) RCT no. NCT00091637.

Background: Although spontaneous reperfusion (SR) prior to primary percutaneous coronary intervention (pPCI) is associated with improved outcomes, its pathophysiology remains unclear. The objective of the study was to explore associations between SR in ST-segment elevation myocardial infarction (STEMI) using a multimarker cardiovascular proteins strategy METHODS: We evaluated STEMI patients from the Assessment of Pexelizumab in Acute Myocardial Infarction trial treated with pPCI within 6 hours from symptom onset. SR was core laboratory-defined as pre-PCI Thrombolysis in Myocardial Infarction flow 2 or 3. Ninety-one cardiovascular disease-related serum biomarkers drawn prior to PCI were analyzed using a high-throughput "targeted discovery" panel. Expression levels for individual biomarkers were compared between patients with/without SR. A hierarchical clustering method of biomarkers identified clusters of biomarkers that differentiated the 2 groups. Associations between individual biomarkers and clusters with SR were further evaluated by multivariable logistic regression.Results: Of 683 patients studied, 290 had spontaneous reperfusion; those with compared to without SR were more likely noninferior STEMI and had lower clinical acuity and lower baseline levels of troponin and creatine kinase. SR was associated with a lower occurrence of 90-day composite of death, heart failure, or cardiogenic shock. Fifty-two of 91 individual biomarkers were significantly univariably associated with SR. Forty-five remained significant with adjustment for false discovery rate. Using cluster analysis, 26 biomarkers clusters were identified, explaining 72% of total covariance, and 13 biomarker clusters were significantly associated with SR after multivariable adjustment. SR was associated with higher mean expression levels of proteins in all 13 clusters. The cluster most strongly associated with SR consisted of novel proteins across various distinct, yet interlinked, pathobiological processes (kallikrein-6, matrix extracellular phosphoglycoprotein, matrix mettaloproteinaise-3, and elafin).Conclusions: Spontaneous reperfusion prior to pPCI in STEMI was associated with a lower risk of adverse clinical events. These exploratory data from a targeted discovery proteomics platform identifies novel proteins across diverse, yet complementary, pathobiological axes that show promise in providing mechanistic insights into spontaneous reperfusion in STEMI.Condensed Abstract: Spontaneous reperfusion has been established with improved STEMI outcomes, yet its pathobiology is unclear and appears to involve diverse physiological processes. Using a 91-biomarker high-throughput proteomics platform, we studied 683 STEMI patients in the APEX AMI trial (290 had core laboratory-adjudicated pre-PCI TIMI 2/3 flow) and identified 52 proteins that univariably associate with spontaneous reperfusion. Cluster analysis identified 26 biomarker clusters (explaining 72% of total variance), 13 of which, after multivariable adjustment, were significantly associated with spontaneous reperfusion. Four proteins (kallikrein-6, matrix extracellular phosphoglycoprotein, matrix mettaloproteinaise-3, and elafin) across diverse, yet complementary, pathways appear to be associated most strongly with spontaneous reperfusion. [ABSTRACT FROM AUTHOR]

Background: Obesity is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). Whether obesity affects outcomes among those with T2D and atherosclerotic CVD (ASCVD) remains uncertain. Our objective was to investigate the relationship between body mass index (BMI) and ASCVD outcomes among TECOS participants with T2D and ASCVD.Methods: BMI categories were defined as underweight/normal weight (BMI <25 kg/m2), overweight (25-29.9 kg/m2), obese class I (30-34.9 kg/m2), obese class II (35-39.9 kg/m2), and obese class III (≥ 40 kg/m2). Asian-specific BMI categories were applied to Asian participants. Kaplan-Meier survival analysis and Cox proportional hazards models were used to examine associations between baseline BMI and a composite CV outcome (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina).Results: For 14,534 TECOS patients with available BMI, mean age was 65.5 years; 29.3% were female, 32.0% non-White, and 23.1% insulin-treated, with median 3 years' follow-up. At baseline, 11.6% (n = 1686) were underweight/normal weight, 38.1% (n = 5532) overweight, 32.2% (n = 4683) obese class I, 12.4% (n = 1806) obese class II, and 5.7% (n = 827) obese class III. The composite CV outcome occurred in 11.4% (n = 1663) of participants; the outcome risk was lower, compared with under/normal weight, in overweight (HR 0.83, 95% CI 0.71-0.98) and obese class I (HR 0.79, 95% CI 0.67-0.93) individuals. Obesity was not associated with worse glycemic control.Conclusions: The majority of TECOS participants with ASCVD and T2D were overweight or obese, yet overweight or obese class I individuals had lower CV risk than those who were under/normal weight. These results suggest the presence of an obesity paradox, but this paradox may reflect an epidemiological artifact rather than a true negative association between normal weight and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: The effects of β-blocker therapy in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) are unclear. We sought to evaluate associations between β-blocker use in T2D with ASCVD and cardiovascular (CV) outcomes.Methods: In patients with T2D and ASCVD enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), an inverse probability of treatment-weighted Cox proportional hazards model was used to examine the association between baseline β-blocker therapy (at randomization) and the primary CV composite (defined as CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for unstable angina), including in subgroups with prior MI and heart failure (HF); other outcomes evaluated included individual components of the primary composite, hospitalization for HF, and severe hypoglycemic events.Results: Of the 14,671 patients randomized, 9322 (64%) were on a β-blocker at baseline; these patients were more likely to have prior MI or HF. Over a median 3.0 (25th, 75th percentile: 2.2, 3.6) years, the risk of the primary CV composite was significantly higher with baseline β-blocker use versus no β-blocker use (4.5 vs. 3.4 events/100-patient years, adjusted hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05-1.29); no significant interaction was noted for patients with versus without prior MI or HF. Baseline β-blocker use was not associated with risks for severe hypoglycemic events (HR 1.14, 95% CI 0.88-1.48).Conclusions: In this observational analysis of T2D and ASCVD, baseline β-blocker use was not associated with risks for severe hypoglycemia yet also was not associated with CV risk reduction over 3 years of follow-up, supporting a randomized examination of chronic β-blocker therapy in this patient population. (TECOS ClinicalTrials.gov number, NCT00790205). [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2008.07.016 Byline: Michelle M. Graham (a), Cynthia M. Westerhout (b), Padma Kaul (a)(b), Colleen M. Norris (c), Paul W. Armstrong (a)(b) Abstract: Patients with acute coronary syndromes (ACS) may experience nonspecific prodromal symptoms before their cardiac event. We used population-level data to determine the rate at which such patients seek medical attention for these symptoms, whether sex differences are present, and if an association between prodromes and 1-year mortality exists. Author Affiliation: (a) Department of Medicine, University of Alberta, Edmonton, Alberta, Canada (b) Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada (c) the Faculty of Nursing, University of Alberta, Edmonton, Alberta, Canada Article History: Received 16 April 2008; Accepted 21 July 2008 Article Note: (footnote) Analyses for this article were supported by an operating grant (MOP-62864) from the Canadian Institutes of Health Research (CIHR) (Ottawa, Ontario, Canada). Dr Kaul is supported by a CIHR New Investigator award and an Alberta Heritage Foundation for Medical Research Population Health Investigator award. Dr. Norris is supported by a CIHR New Investigator Award.

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a known clinical conundrum with limited investigation. Using a large population-based cohort, we examined the incidence, demographic profile, use of evidence-based medicines (EBM) and clinical outcomes of MINOCA patients. Methods Patients hospitalized with a primary diagnosis of MI who underwent coronary angiography between 01/04/2002 and 31/03/2014 in Alberta, Canada, were included in the study. Comparisons were made between patients with MINOCA versus obstructive coronary disease (OCD). The primary composite endpoint was 1-year all-cause death or re-MI. Results Of 35,928 patients hospitalized with MI, 2092 (5.8%) had MINOCA. In-hospital mortality rate was 0.8% among MINOCA, and 2.7% among patients with OCD ( p  < 0.0001). At 6 months, cardiovascular EBM rates were significantly lower among MINOCA patients compared to OCD patients. One-year death/re-MI rate was 5.3% in MINOCA and 8.9% in patients with OCD (adjusted hazard ratio (AHR) 0.75, 95% confidence interval (CI) 0.62–0.92, p  < 0.0001). Five-year mortality rates were 10.9% in MINOCA and 16.0% in patients with OCD. Upon further stratification, 770 (36.8%) of MINOCA patients had no angiographic evidence of CAD (i.e. normal angiograms). EBM rates were even lower among these patients. One-year death/re-MI rate among these patients was 3.9% as compared to 6.1% among MINOCA patients with stenosis <50% (AHR 0.68, 95% CI 0.44–1.07, p  = 0.028). Conclusions The population-level incidence of MINOCA is approximately 5%. Despite their apparently benign anatomic findings, efforts must be made to improve secondary prevention strategies to reduce the burden of long-term adverse outcomes in this population. [ABSTRACT FROM AUTHOR]

Background: Most patients with acute heart failure (AHF) admitted to critical care units (CCUs) are low acuity and do not require CCU-specific therapies, suggesting that they could be managed in a lower-cost ward environment. This study identified the predictors of clinical events and the need for CCU-specific therapies in patients with AHF.Methods: Model derivation was performed using data from patients in the ASCEND-HF trial cohort (n=7,141), and the Acute Heart Failure Emergency Management community-based registry (n=666) was used to externally validate the model and to test the incremental prognostic utility of 4 variables (heart failure etiology, troponin, B-type natriuretic peptide [BNP], ejection fraction) using net reclassification index and integrated discrimination improvement. The primary outcome was an in-hospital composite of the requirement for CCU-specific therapies or clinical events.Results: The primary composite outcome occurred in 545 (11.4%) derivation cohort participants (n=4,767) and 7 variables were predictors of the primary composite outcome: body mass index, chronic respiratory disease, respiratory rate, resting dyspnea, hemoglobin, sodium, and blood urea nitrogen (c index=0.633, Hosmer-Lemeshow P=.823). In the validation cohort (n=666), 87 (13.1%) events occurred (c index=0.629, Hosmer-Lemeshow P=.386) and adding ischemic heart failure, troponin, and B-type natriuretic peptide improved model performance (net reclassification index 0.79, 95% CI 0.046-0.512; integrated discrimination improvement 0.014, 95% CI 0.005-0.0238). The final 10-variable clinical prediction model demonstrated modest discrimination (c index=0.702) and good calibration (Hosmer-Lemeshow P=.547).Conclusions: We derived, validated, and improved upon a clinical prediction model in an international trial and a community-based cohort of AHF. The model has modest discrimination; however, these findings deserve further exploration because they may provide a more accurate means of triaging level of care for patients with AHF who need admission. [ABSTRACT FROM AUTHOR]

Objectives This study investigated the relationship between time to invasive assessment and outcomes among ST-segment elevation myocardial infarction patients randomized to early angiography after fibrinolysis. Background The optimal timing of coronary angiography after fibrinolysis and the association with clinical outcomes is uncertain. Methods Patient-level data from 6 randomized trials, with a median time to angiography <12 h after fibrinolysis, were pooled. The primary endpoint was 30-day death or reinfarction. The key secondary endpoint was in-hospital major bleeding. The relationship between fibrinolysis to angiography time and symptom onset to angiography time with outcomes was studied using 2- and 4-h intervals, respectively, and in multivariable models. Results Among 1,238 patients, the median fibrinolysis to angiography time was 165 min, and the median symptom onset to angiography time was 5.33 h. The primary and key secondary endpoints occurred in 5.7% and 4.7%, respectively. These main endpoints did not vary significantly with increasing fibrinolysis to angiography time. Early angiography (<2 h) after fibrinolysis was not associated with increased bleeding. Recurrent ischemia increased with increasing fibrinolysis to angiography time (3.7% to 7.9%, p for trend = 0.02). Thirty-day and 1-year death/reinfarction and 30-day recurrent ischemia increased significantly with increasing symptom onset to angiography time. Neither fibrinolysis to angiography time nor symptom onset to angiography time was an independent predictor of the primary endpoint. Only symptom onset to angiography time was an independent predictor of 1-year death/reinfarction (hazard ratio: 1.07, 95% confidence interval: 1.02 to 1.12, p = 0.01). Conclusions Very early angiography (<2 h) after fibrinolysis was not associated with an increased risk of 30-day death/reinfarction or in-hospital major bleeding, and angiography within 4 h after fibrinolysis was associated with reduced 30-day recurrent ischemia. A shorter symptom onset to angiography time (<4 h) was associated with reduced 30-day and 1-year death/reinfarction and 30-day recurrent ischemia. In the current environment of regional networks of 24/7 primary percutaneous coronary intervention (PCI) centers, the clinical implication of these findings is that patients initially treated with fibrinolysis should also be promptly transferred to the nearest PCI center for immediate angiography and PCI. (Early Percutaneous Coronary Intervention [PCI] After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction [STEMI] Patients; NCT01014182 ) [ABSTRACT FROM AUTHOR]

Background The relationship of metabolic syndrome and its individual components (obesity, hypertension, glucose intolerance, high triglycerides, and low high-density lipoprotein cholesterol) with 1-year mortality in non-ST-segment elevation acute coronary syndromes (NSTE ACS) patients is not known. Methods The association of metabolic syndrome (and its individual components) with all-cause mortality within 1 year was assessed in NSTE ACS patients enrolled in the EARLY ACS trial. Adjusted hazard ratio (HR) and 95% CIs are reported. Results Of 9,406 patients, 2,596 (27.6%) had metabolic syndrome. Compared with those without metabolic syndrome, patients with this syndrome were younger, were more often female, and had a higher prevalence of comorbid conditions and higher-risk presenting features. Metabolic syndrome was not associated with increased 1-year mortality (HR 1.20, 95% CI 0.97-1.47; P = .09). The risk of 1-year mortality varied across the individual components: high-density lipoprotein <40 mg/dL (men)/<50 mg/dL (women; or dyslipidemia) was associated with higher risk (HR 1.52, 95% CI 1.15-2.02), and triglycerides >150 mg/dL (or dyslipidemia) was associated with lower risk (HR 0.66, 95% CI 0.54-0.81), whereas the other components (ie, body mass index >30 kg/m², fasting plasma glucose >100 mg/dL or diabetes, systolic blood pressure >130 mm Hg or diastolic >85 mm Hg [or hypertension]) were associated with neutral risk of this event. Conclusions The individual components of metabolic syndrome had varying associations with 1-year mortality, and as an integrated diagnosis, metabolic syndrome was not significantly associated with 1-year mortality. Thus, patient case-mix of the studied NSTE ACS population may influence the observed relationship of metabolic syndrome with subsequent cardiovascular events. # [ABSTRACT FROM AUTHOR]

Objectives To evaluate quantitative relationships between baseline Q-wave width and 90-day outcomes in ST-segment elevation myocardial infarction (STEMI). Background Baseline Q-waves are useful in predicting clinical outcomes after MI. Methods 3589 STEMI patients were assessed from a multi-centre study. Results 1156 patients of the overall cohort had pathologic Q-waves. The 90-day mortality and the composite of mortality, congestive heart failure (CHF), or cardiogenic shock (p < 0.001 for both outcomes) rose as Q-wave width increased. After adapting a threshold ≥ 40 ms for inferior and ≥ 20 ms for lateral/apical MI in all patients (n = 3065) with any measureable Q-wave we found hazard ratios (HR) for mortality (HR: 2.44, 95% confidence interval (CI) (1.54-3.85), p < 0.001) and the composite (HR: 2.32, 95% CI (1.70-3.16), p < 0.001). This improved reclassification of patients experiencing the composite endpoint versus the conventional definition (net reclassification index (NRI): 0.23, 95% CI (0.09-0.36), p < 0.001) and universal MI definition (NRI: 0.15, 95% CI (0.02-0.29), p = 0.027). Conclusions The width of the baseline Q-wave in STEMI adds prognostic value in predicting 90-day clinical outcomes. A threshold of ≥ 40 ms in inferior and ≥ 20 ms for lateral/apical MI enhances prognostic insight beyond current criteria. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: We evaluated inter-reader agreement of the ST-segment between two electrocardiogram (ECG) core laboratories. Background: Accurate measurement of the ST-segment is key to diagnosis and management of acute coronary syndromes (ACS). Clinical trials also rely on adherence to the pre-specified ECG eligibility criteria. Methods: 150 patients (100 ST-segment elevation (STE)-ACS, 50 non-STE-ACS) were selected. An experienced ECG reader from each laboratory measured ST-segment deviation on the baseline ECGs (nearest 0.1mm). Results: ∑ST-segment deviation showed excellent inter-reader agreement (R=0.965, intraclass correlation coefficient (ICC) 0.949, 95% CI (0.930–0.963)). Similar agreement was observed when ∑ST-segment elevation (∑STE) and ∑ST-segment depression (∑STD) were assessed separately. Better agreement was evident in STE-ACS cohort (ICC (95% CI): 0.968 (0.953–0.978, 0.969 (0.954–0.979), 0.931 (0.899–0.953)) compared to NSTE-ACS patients (ICC (95% CI): 0.860 (0.768–0.917), 0.816 (0.699–0.890), 0.753 (0.605–0.851) across measurement of ∑ST-segment deviation, ∑STE, and ∑STD. Conclusions: We demonstrated excellent agreement on ST-segment measurements between two experienced readers from two ECG core laboratories. [Copyright &y& Elsevier]

Background: Female sex is an established risk factor for bleeding, which is an important safety end point in patients presenting with non–ST-segment elevation acute coronary syndromes (NSTE ACS). However, it is unknown whether the association between bleeding and mortality is modulated by sex in this patient population. Methods: We examined the interaction between sex and bleeding and 30-day mortality outcomes among 2,975 women and 6,431 men with high-risk NSTE ACS enrolled in the EARLY ACS trial. The Global Utilization of Strategies to Open Occluded Arteries (GUSTO) criteria were used to identify moderate or severe bleeds. Results: Women were older and had more comorbid disease compared with men. Bleeding rates were higher among women (8.2%) than among men (5.5%; P < .01). However, the association of bleeding and 30-day mortality was stronger among men (odds ratio 5.8, 95% CI 3.9-8.8) than among women (odds ratio 1.5, 95% CI 0.8-2.9; sex * bleeding interaction P < .01). Sex differences in the association of bleeding and mortality persisted in a landmark analysis of 120-hour survivors. Conclusions: In a contemporary high-risk NSTE ACS cohort, women had higher bleeding rates than did men. Paradoxically, the association between bleeding and mortality was worse among men than among women. [Copyright &y& Elsevier]

Background: Lead aVR ST-segment deviation has been associated with increased mortality in ST-elevation myocardial infarction patients treated with fibrinolysis. However, its prognostic value in a contemporaneous population undergoing primary percutaneous coronary intervention is unknown. Methods and Results: A core laboratory examined the 12-lead baseline electrocardiogram in 5,683 patients presenting within 6 hours of symptom onset in the APEX-AMI trial, and readers were blinded to study treatment and clinical outcomes. aVR ST-deviation was significantly associated with 90-day death when compared with patients with no aVR ST-deviation (aVR ST-depression [ST-D] 5%, aVR ST-elevation [ST-E] 10.2%, no ST-deviation [N] aVR 3.8%, P < .001). After multivariable adjustment, aVR ST-E was strongly associated with 90-day death in inferior myocardial infarction (MI) (adjusted hazard ratio [HR] 5.87, 95% CI 2.09-16.5), whereas aVR ST-D was associated with excess mortality in noninferior MI (1.53, 1.06-2.22; P [interaction] < .001). aVR ST-E was also significantly associated with the presence of left main coronary (N aVR 1.8%, aVR ST-E 7.7%, P ≤ .001) and multivessel coronary disease (N aVR 41.3%, aVR ST-E 53.3%, P ≤ .001). Conclusions: Lead aVR ST-deviation is common, occurring in one-third of all ST-elevation myocardial infarction patients and independently associated with increased 90-day death. Myocardial infarction location modulates the prognostic significance of aVR ST-deviation such that lead aVR ST-E in inferior MI and ST-D in noninferior MI represent 2 high-risk groups. There was also more frequent advanced coronary disease in patients with aVR ST-E. [Copyright &y& Elsevier]

Background: Aborted myocardial infarction (AbMI) in patients with ST-elevation MI defined by ST resolution with less than 2-fold elevation in biomarkers has been previously reported. We examined the association among AbMI, other metrics of infarct size, and left ventricular (LV) function defined by cardiac magnetic resonance (CMR). Methods: A total of 5745 patients with ST-elevation MI enrolled in the APEX-AMI trial, and 73 who were part of the CMR substudy within 3 to 5 days of randomization were evaluated. Core laboratories analyzed electrocardiograms, angiograms, and CMR images. Results: Aborted MI (peak creatine kinase/creatine kinase MB <2× upper limit of normal) with typical evolutionary electrocardiogram changes was observed in 11% (437/3938) overall and in 19% (14/73) of patients within the CMR study. Patients with AbMI were older (62 vs 60 years, P = .003) and tended to achieve complete STE-resolution post–percutaneous coronary intervention (≥70% resolution: 64% vs 32%; P = .076) compared with patients with MI. Cardiac magnetic resonance revealed that patients with AbMI had a smaller infarct size (4.7% vs 14.9% LV, P < .001), less “no reflow” (0.9% vs 1.7% LV, P = .017), enhanced LV function (ejection fraction 54.4% vs 46.5%, P = .064), smaller LV end-systolic volumes (46.5 mL vs 67.2 mL, P = .009), and less transmurality (21.4% vs 50.9% with at least 1 segment with >75% wall thickness, P = .046) when compared with patients with MI. Conclusions: Patients with AbMI had smaller subendocardial infarcts with enhanced LV size and function. Cardiac magnetic resonance provides corroborative evidence of AbMI and insights into its pathophysiology, specifically rapid successful reperfusion leading to limitation of the “wavefront” of infarct to the subendocardium. [ABSTRACT FROM AUTHOR]

Introduction: Contemporary non–ST-elevation myocardial infarction–acute coronary syndrome guidelines emphasize early-risk stratification and optimizing therapy including an invasive strategy in high-risk patients. To assess the feasibility of initiating this strategy in the prehospital environment, we examined how such patients are transported to hospital, their risk profile, and the proportion potentially eligible for such a strategy. Methods: Consecutive patients with ST-segment elevation myocardial infarction admitted in Edmonton were studied between September and November 2008 and divided according to their mode of transport to hospital: emergency medical services (EMS) versus self-presenting. Baseline characteristics, GRACE Risk Score, blinded core laboratory electrocardiogram analysis, cardiac biomarkers, in-hospital procedures, and outcomes were analyzed. Results: Thirty-five percent (93/263) of patients presented via EMS and often to percutaneous coronary intervention hospitals, that is, 64.5% versus 44.1% (P = .0016). They were older (75 vs 62 years, P < .001), more often female (43% vs 28.1%, P < .001), diabetic (34.4% vs 22.9%, P = .045), and hypertensive (72.0% vs 57.1%, P = .017) and had higher GRACE Risk Scores (median 166 vs 130, P < .001). Electrocardiogram analysis revealed more baseline Q waves (38.8% vs 25.5%, P = .031) and ST depression ≥2 mm (P = .027) in EMS-transported patients. Fewer EMS patients underwent cardiac catheterization (60.2% vs 88.2%, P < .001), and a paradoxical relationship existed between catheterization rates and GRACE Risk Score in the total cohort (low-risk: 93.4% vs high-risk: 59.3%, P < .001). The composite of death/re–myocardial infarction/congestive heart failure/shock was greater in EMS patients (unadjusted odds ratio 3.96, 95% CI 1.80-8.69, P = .001); these differences were attenuated after GRACE Risk Score adjustment. Conclusion: Regional strategies using risk-based triage, early medical therapy, and timely triage to percutaneous coronary intervention centers represents an unrealized opportunity to enhance ST-segment elevation myocardial infarction care. [Copyright &y& Elsevier]

Background: Traditional time-to-event analysis assigns equal weight to the first event in the composite end point. This is counterintuitive to many stakeholders. Methods: We constructed weights for components of a composite efficacy end point and a net clinical outcome by including metrics of safety and efficacy and compared the weighted with the traditional approach. Through an externally validated, clinician-investigator Delphi panel, the relative severity of individual components of a composite end point (30-day death, recurrent myocardial infarction, cardiogenic shock, and congestive heart failure) was determined. The net clinical outcome was assessed through the incorporation of risk thresholds for safety events (intracranial hemorrhage and major systemic bleeding). These weights were then applied to a modified analysis of the ASSENT-3 trial. Results: The weights for the efficacy composite were as follows: death, 1.0; shock, 0.5; congestive heart failure, 0.3; and recurrent myocardial infarction, 0.2. The traditional time-to-first-event approach demonstrated a comparable advantage for both enoxaparin (enox) and abciximab (abx) over unfractionated heparin (P = .05), whereas the weighted efficacy analysis suggested an advantage for enox and similar outcomes between unfractionated heparin and abx (P = .2). The apparent advantage of enox was attenuated when the net clinical outcome was examined; the apparent efficacy of abx combination therapy was also diminished by an elevated major systemic bleeding rate (P < .001). Conclusion: This novel approach adds an alternative dimension to treatment evaluation by more efficiently incorporating the differential value of all events in each patient. Further development and application of this approach to future trial design and analysis are warranted. [ABSTRACT FROM AUTHOR]

Background: The CAPTIM trial suggested a survival benefit of prehospital fibrinolysis (FL) compared to primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) with a presentation delay of <2 hours. We examined the relationship between reperfusion strategy and time from symptom onset on 1-year mortality in a combined analysis of 1,168 patients with STEMI. Methods: Individual patient data from CAPTIM (n = 840, 1997-2000) and the more recent WEST trial (n = 328, 2003-2005) were pooled. Results: Median age was 58 years, 81% were men, and 41% had anterior myocardial infarction; 640 patients were randomized to FL versus 528 patients to PCI. Both arms received contemporary adjunctive medical therapy. Presentation delay (ie, symptom onset to randomization) was similar in FL and PCI patients (median 105 [72-158] vs 106 [74-162] minutes, P = .712). Rescue PCI after FL occurred in 26% and 27%, and 30-day PCI, in 70% and 71% in CAPTIM and WEST, respectively. Mortality was not different between FL and PCI (4.6% vs 6.5%, P = .263); however, the interaction between presentation delay and treatment was significant (P = .043). Benefit with FL was observed with time <2 hours (2.8% [FL] vs 6.9% [PCI], P = .021, hazard ratio [HR] 0.43, 95% CI 0.20-0.91), whereas beyond 2 hours, no treatment difference was observed (6.9% [FL] vs 6.0% [PCI], P = .529, HR 1.23, 95% CI 0.61-2.46). Conclusions: A strategy of early FL demonstrated a reduction in 1-year mortality compared to primary PCI in early presenters. Time from symptom onset should be a key consideration when selecting reperfusion therapy for STEMI. [Copyright &y& Elsevier]

Background: ST-elevation myocardial infarction (STEMI) patients with a prior MI history have worse outcomes. The prognostic significance of silent MI (pathologic Q waves outside the ST-elevation territory) in STEMI is unclear. Methods: A total of 5,733 STEMI patients from 296 clinical centers in 17 countries were classified as (1) silent MI—baseline Q waves outside the infarct-related artery territory and no history of prior MI, (2) history of prior MI (HxMI), or (3) no prior MI. Results: Of 5,733 STEMI patients, 419 (7.3%) had silent MI, 693 (12.1%) had HxMI, and 4,621 (80.6%) had no prior MI. Ninety-day death and death/congestive heart failure/shock were higher in patients with HxMI (8.4% and 15.3%, respectively) and silent MI (6.7% and 13.9%, respectively) compared with patients with no prior MI (4.0% and 9.1%, respectively) (P ≤ .001 for all). After baseline adjustment, patients with HxMI were at increased risk for 90-day death (adjusted hazard ratio [HR] 1.62, 95% CI 1.18-2.21), whereas both those with HxMI and those with silent MI had increased risk of 90-day death/congestive heart failure/shock compared with those with no prior MI (adjusted HR 1.54, 95% CI 1.23-1.93 and adjusted HR 1.46, 95% CI 1.10-1.93, respectively). Conclusions: Seven percent of STEMI patients had a silent MI. They represent a novel subgroup at increased risk comparable to those with known prior MI. Hence, in future studies, acquiring baseline Q wave data outside the distribution of acute injury should broaden the prognostic insights from STEMI patients with a prior MI. [ABSTRACT FROM AUTHOR]

Abstract: Background: Atrial infarction reportedly occurs in 0.7% to 52% of ST-elevation myocardial infarctions (STEMIs), up to two thirds of whom develop atrial fibrillation and flutter (AF). Prospective validation of electrocardiographic atrial infarction patterns is lacking. Hence, in STEMI patients treated with primary percutaneous coronary intervention, we examined whether baseline atrial electrocardiographic changes or atrial infarction patterns predicted new AF or mortality. Methods: Within the Assessment of Pexelizumab in Acute Myocardial Infarction trial, a nested case-control study was conducted. Patients with new AF were matched 1:1 with controls, and baseline atrial electrocardiographic variables were examined. Results: Abnormal P wave morphology (Liu minor criterion for atrial infarction) was significantly associated with new AF (adjusted odds ratio, 1.68; 1.03-2.73). This was also independently associated with 90-day mortality in the overall case-control cohort (adjusted hazard rate, 1.90; 1.04-3.46) and among patient with new-onset AF (adjusted hazard rate, 2.43; 1.22-4.84). Conclusions: Abnormal P wave morphology significantly predicted new AF and 90-day mortality in STEMI patients. [Copyright &y& Elsevier]

Objectives: We sought to compare outcomes in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) with or without previous coronary artery bypass grafts (CABG). Background: Limited information exists regarding procedural success and clinical outcomes of STEMI patients with CABG undergoing primary PCI. Methods: The APEX-AMI (Assessment of Pexelizumab in Acute Myocardial Infarction) trial was a randomized, placebo-controlled trial of pexelizumab in STEMI patients with planned primary PCI: 128 of 5,745 (2.2%) patients had prior CABG. Clinical/procedural characteristics, culprit vessel (infarct-related artery [IRA]), and 90-day clinical outcomes were compared. Results: Patients with previous CABG were more frequently men, older, had a higher incidence of comorbidities and multivessel disease. In patients with versus without prior CABG, PCI was performed less frequently, that is, 78.9% versus 93.9%; of those with prior CABG receiving PCI, Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was also restored less often, that is, 82.5% versus 91.6% (both p < 0.001). In prior CABG, there was a nearly even designation of the IRA as a bypass graft (n = 63) versus a native vessel (n = 55): IRA post-PCI TIMI flow grade 3 was achieved in 66.7% versus 88.0%, respectively (p = 0.043). Prior CABG patients had increased 90-day death and composite 90-day death/congestive heart failure/shock. Excess death remained significant after multivariable adjustment (hazard ratio: 1.9, 95% confidence interval: 1.08 to 3.33, p = 0.025). When prior CABG patients were stratified by the type of IRA, there was further discrimination of the increased 90-day death, that is, 19% bypass graft (n = 63) versus 5.7% native vessel (n = 55, p = 0.05), respectively. Conclusions: Prior CABG patients with STEMI are less likely to undergo acute reperfusion, have worse angiographic outcomes following primary PCI, and higher 90-day mortality. These findings are especially applicable when the IRA was a bypass graft. [Copyright &y& Elsevier]

Objectives: The aim of this study was to obtain a valid estimate of the clinical effects of primary percutaneous coronary intervention (PPCI) in relation to age. Background: Treatment with PPCI is most beneficial in high-risk myocardial infarction patients. Paradoxically, elderly patients, who are at increased risk of adverse outcome, are often withheld PPCI. Methods: Individual patient data were obtained from 22 randomized trials (n = 6,763) evaluating the clinical effects of PPCI versus fibrinolysis (FL). Differences in 30-day death, repeat myocardial infarction, and stroke between patients randomized to FL and PPCI were determined in 5 age-strata: ≤50, >50 to 60, >60 to 70, >70 to 80, and >80 years. Treatment effects are reported as odds ratios (ORs) and 95% confidence intervals (CI). Multivariable logistic regression analyses, which included age × treatment interaction, were applied to examine evidence of heterogeneity in age-specific ORs. Results: Thirty-day death increased with increasing age and ranged from 1.1% (FL) and 1.8% (PPCI) in patients ≤50 years to 26.4% and 18.3% in patients >80 years of age. The point estimate of treatment effect (overall adjusted OR: 0.65; 95% CI: 0.52 to 0.79) was compatible with a mortality reduction favoring PPCI in all age-strata (except in patients ≤50 years of age), and 95% CIs were largely overlapping. There was no evidence of heterogeneity in ORs between age categories. Similar results were observed for repeat myocardial infarction and stroke. Conclusions: In this analysis of randomized trials, the reduction in clinical end points by PPCI was not influenced by age. Hence, age per se should not be considered an exclusion criterion for the application of PPCI. [Copyright &y& Elsevier]

Background: Reperfusion with primary percutaneous intervention (PCI) in ST-segment elevation myocardial infarction leads to improved clinical outcomes. The contribution angiographic vs electrocardiographic reperfusion parameters confer on prognosis is unclear. Methods: A prespecified subset of the APEX-AMI trial patients was analyzed by independent angiographic and electrocardiographic core laboratories (n = 1,018). Angiographic reperfusion after PCI and electrocardiogram 30 minutes post-PCI were assessed. Results: Of the 941 patients in the angiographic substudy, 796 (85%) attained post-PCI Thrombolysis In Myocardial Infarction (TIMI) flow 3 and 852 (91%) had TIMI Myocardial Perfusion Grade (TMPG) 2/3. There were 664 (71%) patients with residual ST elevation (ST-E) <2 mm. Ninety-day mortality and death/CHF/shock were lower in patients with TIMI flow 3 vs <3 (1.9% vs 6.2%, P = .002; 5.8% vs 10.4%, P = .044) and those with TMPG 2/3 vs 0/1 (2.0% vs 7.9%, P = .001; 6.0% vs 11.9%, P = .028). Patients with residual ST-E <2 mm had similar rates of mortality as those with ≥2 mm (2.3% vs 3.3%, P = .374) but lower rates of death/CHF/shock (5.2% vs 9.6%, P = .013). After multivariable adjustment, only post-PCI TMPG 2/3 was significantly associated with survival (P = .001), whereas residual ST-E (P = .606) and post-PCI TIMI flow grade (P = .086) were not. Conversely, residual ST-E ≥2 mm (P = .012) rather than angiographic reperfusion was associated with the composite of death/CHF/shock events. Conclusion: Angiographic and electrocardiographic estimates of reperfusion with primary PCI in ST-segment elevation myocardial infarction provide different and complementary predictions of morbidity and mortality. [Copyright &y& Elsevier]

Background: Rescue percutaneous coronary intervention (PCI) is efficacious after clinical failure of fibrinolytic therapy and is recommended for those with persistent ischemia, hemodynamic, or electrical instability. We sought to describe the frequency of fibrinolytic failure (rescue eligibility) as well as the patient characteristics associated with rescue eligibility, rescue referral, and PCI. Methods and Results: Eligibility, indication, and referral for guideline-based rescue PCI were adjudicated in 221 patients enrolled in the WEST trial. WEST treated patients at earliest medical contact and used a tenectaplase/enoxaparin regimen. Ninety patients (41%) were adjudicated with acute myocardial infarction as rescue eligible of whom 68 were referred for rescue PCI. Baseline characteristics did not predict rescue eligibility or referral. Emergency angiography before PCI performed a median of 82 minutes (interquartile range 50-99) after rescue referral showed TIMI flow grade 2 or 3 in 34 (50%). Percutaneous coronary intervention was adjudicated as successful in 58 of 60 attempts. Procedures began approximately 45 minutes sooner in patients initially admitted to PCI-capable hospitals. Compared to those with clinically successful fibrinolytic therapy, rescue eligible patients demonstrated higher median peak creatine phosphokinase (1889 [1243-3746] vs 999 [440-2048], P < .01) and 30-day median NT-proBNP levels (748 [391-1916] vs 431 [153-1016], P < .01). Conclusions: Rescue eligibility determined by guideline criteria is common after contemporary fibrinolysis and is not predicted by conventional baseline characteristics. Half of rescue-referred patients are patent at angiography: although contemporary PCI success rates are high, rescue eligibility is associated with larger infarctions. [ABSTRACT FROM AUTHOR]

Background: Although relationships between chronic Chlamydia pneumoniae (Cpn) infection and the risk of coronary events in stable coronary artery disease patients have been reported, a similar link in acute coronary syndrome (ACS) patients has not been consistently observed. Methods: In a nested case-control substudy of the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial, 295 cases (30-day death/myocardial infarction [MI]) were matched by age, sex, baseline creatine kinase–myocardial kinase, and smoking status with 295 control subjects. To test the hypothesis on 1-year mortality, another subset (n = 276) was drawn from the 590-patient cohort; 138 patients who died at 1 year plus the matching controls who survived at 1 year. We measured Cpn IgG and IgA antibody titers in baseline serum with microimmunofluorescence. Conditional logistic regression was used to quantify the prognostic relevance seropositivity (IgG ≥1:32; IgA ≥1:16) and elevated titer levels. Results: The prevalence of Cpn IgG and IgA was similar between cases and controls (30-day death/MI: IgG, 80% vs 85%, P = .126; IgA, 45% vs 37%, P = .079), and were not statistically significant predictors of 30-day death/MI after baseline adjustment. Likewise, the 1-year death cohort had comparable proportions of Cpn IgG and IgA among cases and controls (86% vs 91% [P = .265] and 49% vs 43% [P = .334], respectively), and did not add prognostic value. Conclusions: These findings are in concert with study results suggesting that chronic Cpn infection is not associated with 30-day death/MI or 1-year mortality in non-ST elevation ACS. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to develop 30-day and 1-year risk stratification models for non–ST-segment elevation acute coronary syndrome (NSTE-ACS) patients that incorporate quantitative ST-segment depression and novel biomarkers. Background: Several novel biomarkers have changed the risk profile of ACS; thus, the reassessment of traditional indicators such as ST-segment depression in this new context is warranted. Methods: Multivariable logistic regression was used to identify significant predictors of 30-day death and death/myocardial infarction (MI) and 1-year mortality in 7,800 NSTE-ACS patients enrolled in the GUSTO-IV (Global Utilization of Strategies to Open Occluded Arteries-IV ACS) trial between 1998 and 2000. Results: Among all other predictors, the degree of ST-segment depression had the highest prognostic value for 30-day death, 30-day death/MI, and 1-year death. Troponin T (TnT), creatinine clearance, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart rate, and age were also highly influential on adverse outcomes. Unlike TnT and NT-proBNP, C-reactive protein was only predictive of long-term death. In contrast to mortality, the contribution of TnT to predicting 30-day death/MI increased, whereas NT-proBNP’s role was attenuated. The discriminatory power was excellent (c-index [adjusted for over-optimism]: 0.82 [30-day death]; 0.72 [30-day death/MI]; 0.81 [1-year]). Conclusions: In this large contemporary study of NSTE-ACS patients, novel insights into risk stratification were observed—in particular, the utility of quantitative ST-segment depression and multiple biomarkers. Collection of these indicators in future NSTE-ACS populations is recommended to evaluate generalizability and clinical application of these findings. [Copyright &y& Elsevier]

Randomized controlled trials (RCT) often enroll patients with different demographics and outcomes than a broader non-RCT population. To provide context for the VICTORIA RCT, we designed a registry of patients with worsening heart failure (WHF) to characterize baseline characteristics, outcomes, and potential reasons for non-participation in a RCT. 51 VICTORIA RCT sites were selected from Canada and the US. Eligible patients for the registry included those with chronic HF, currently or recently hospitalized for HF, and EF<45%; no other exclusions were applied. Sites identified 50 patients for retrospective chart data abstraction sampled over a series of 4 time points from February 2018 to January 2019 during the VICTORIA enrollment period. VICTORIA RCT eligibility criteria were applied and non-mutually exclusive reasons for non-inclusion were captured, if available. 1-year outcomes were estimated by the MAGGIC score. 2056 patients were enrolled in the registry, of whom 61% (n = 1256) were not eligible for the RCT, 37% (n = 766) were eligible but not enrolled, and 2% (n = 34) were enrolled in the RCT. Registry patients had a median age of 70, 33% were women, 63% were white, 48% had atrial fibrillation on ECG, and 59% had CAD. Median EF was 25%, median eGFR was 50 ml/min/1.73m2 and median NT-proBNP at discharge was 4376 pg/ml. The median MAGGIC risk score was 28 (23-32) indicating a 20.9% (13.4-29.2%) predicted 1-year mortality, similar to the all-cause mortality seen in the VICTORIA RCT (21.2%). Reasons for ineligibility in the RCT included long-acting nitrate use (23%), SBP <100 mmHg (12%), and substance use (11%); other exclusion criteria <10% (Fig). For eligible patients, reasons for non-participation in the RCT included lack of interest (28%), poor compliance (25%), inability to complete follow-up (23%), too sick (19%), unable to provide consent (17%), and distance from site (15%). Patients with WHF in a contemporaneous registry exhibit high-risk features with many having modifiable reasons for exclusion from an RCT. Several reasons for non-participation in an RCT indicate opportunities for improving enrollment to ensure generalizability. [ABSTRACT FROM AUTHOR]

Background Elderly patients with ST-segment elevation myocardial infarction (STEMI) have worse outcomes and a greater risk of intracranial bleeding than nonelderly patients. Baseline characteristics, clinical outcomes, and the relationship of the tenecteplase (TNK) dose reduction to the efficacy, safety, and electrocardiographic indicators of reperfusion efficacy were evaluated in STEMI patients ≥75 years. Methods The STREAM trial evaluated early presenting STEMI patients who could not undergo primary percutaneous coronary intervention within 1 hour of first medical contact. Because of excess intracranial hemorrhage (ICH) in patients ≥75 years, the dose of TNK was reduced by 50%. Results Before dose amendment, there were 3 (7.1%) of 42 elderly patients with ICH; 2 of these were fatal, whereas no ICH occurred in the 93 elderly patients who received half-dose TNK postamendment. The median extent of ST-segment elevation resolution (≥50%) and proportion of patients with ≥2 mm in the electrocardiogram lead with greatest ST-segment elevation was comparable in elderly patients preamendment and postamendment (63.2% vs 56.0% and 43.6% vs 40.0%, respectively). Patients requiring rescue coronary intervention after TNK was also similar (42.9% vs 44.1%). The primary composite end point (30-day all-cause death, cardiogenic shock, congestive heart failure, and reinfarction) was 31.0% before versus 24.7% postamendment. Conclusions Our data, from a modest-sized population of elderly STEMI patients, indicate that half-dose TNK reduces the likelihood of ICH without compromising reperfusion efficacy. These observations are hypothesis generating and warrant further confirmation in randomized clinical trials in the elderly. [ABSTRACT FROM AUTHOR]

Background The efficacy of a routine invasive strategy early after fibrinolysis in relation to baseline risk status is unclear. We sought to characterize the interaction between patient risk and treatment with routine invasive strategy early after fibrinolysis for ST-segment elevation myocardial infarction. Methods We pooled 2,974 patients from 7 randomized trials of fibrinolysis-treated patients with ST-segment elevation myocardial infarction comparing a routine early invasive strategy with a standard approach of percutaneous coronary intervention (PCI) guided by recurrent ischemia or need for rescue. Cox proportional hazards regression was used to examine the interaction between baseline patient risk classified by Thrombolysis in Myocardial Infarction risk score (low/intermediate: ≤5 [n = 2,697] vs high: >5 [n = 277]) and treatment with routine early invasive strategy. Results Time to PCI after fibrinolysis was longer among patients randomized to standard treatment compared with routine early invasive strategy in the low/intermediate-risk strata (median 11.4 vs 3.5 hours), but was only marginally different between the 2 groups in the high-risk strata (median 4.1 vs 3.5 hours). There was a significant interaction between treatment assignment and risk status for the composite of 30-day death or reinfarction ( P = .01). Compared with standard treatment, routine early invasive strategy was associated with lower 30-day death/reinfarction in the low/intermediate-risk stratum (7.5% vs 4.0%, P < .001), but not in the high-risk stratum (14.9% vs 19.6%, P = .45). Conclusions Although clearly beneficial among the larger subgroup of patients at low/intermediate risk, the benefit of a routine early invasive strategy was not evident in the smaller subgroup of higher-risk patients in the context of an increased requirement for urgent PCI in the comparative standard treatment arm. [ABSTRACT FROM AUTHOR]

Background: Bleeding is a major limitation of antithrombotic therapy among invasively managed non-ST-segment elevation acute coronary syndromes (NSTE-ACS) patients; therefore, we examined the use of radial access and its association with outcomes among NSTE-ACS patients.Methods: Clinical characteristics and geographic variation in radial access were examined, as well as its association with bleeding, red blood cell transfusion and ischemic outcomes (96-hour death/myocardial infarction/recurrent ischemic/thrombotic bailout; 30-day death/myocardial infarction; 1-year death) in the EARLY versus delayed, provisional eptifibatide in acute coronary syndromes trial.Results: Of 9126 patients, 13.5% underwent radial-access catheterization. Female sex, age, weight, and prior revascularization were inversely associated with radial access, and its use varied widely by country (2%-97%). There were fewer GUSTO severe/moderate bleeds and red blood cell transfusions in the radial access group; however, it was attenuated after adjustment (odds ratio 0.73, 95% confidence intervals [CI] [0.50-1.06], P = .094 and 1.00 [0.71-1.40] P = .991). Ischemic outcomes did not differ by access site.Conclusions: In this post hoc analysis of a large clinical trial, there was significant international variation in use of radial access for NSTE-ACS patients undergoing invasive management, and it was preferentially used in those at lower risk for bleeding. Radial approach was not associated with a significant reduction in either bleeding or ischemic outcomes. Further study is needed to determine whether wider application of radial approach to acute coronary syndrome patients at high risk for bleeding improves overall outcomes. [ABSTRACT FROM AUTHOR]

Aims: Dynamic risk models update the risk profile of ST-elevation myocardial infarction (STEMI) patients over the acute period following the event and have implications to clinical practice and research. Methods and Results: Multivariable survival models were developed in 5,745 STEMI patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the APEX-AMI trial to predict 90-day mortality from 4 clinically relevant times: baseline, 2 hours, 24 hours, and 96 hours. Culprit coronary thrombolysis in myocardial infarction flow grade, 30-minute post-PCI worst-lead ST-elevation residual, and in-hospital clinical events were considered in the models. The 90-day mortality was 4.7%; the cumulative proportion of mortality occurring within 2, 24, and 96 hours was 8%, 22%, and 40% respectively. Relative to the baseline risk factors, age and systolic blood pressure remained highly ranked in the post-baseline models. However, the relative importance of heart rate, Killip class, and creatinine declined, whereas markers of coronary reperfusion and in-hospital events (shock, congestive heart failure) became increasingly influential. The c-index increased from 0.819 at baseline to 0.847 at 96 hours. Over the forecasting periods, the proportion of “low-risk” (<1.1% 90-day mortality) patients increased from 20% to 49%. This approach derived from an unfolding series of models reveals the shifting levels of mortality risk from baseline to 96 hours. Conclusion: This novel approach in STEMI patients undergoing primary PCI demonstrates the dynamic nature of risk over time and may prove useful in understanding risk and in clinical decision making. [Copyright &y& Elsevier]

Background: Meta-analyses of randomized trials show that primary percutaneous coronary intervention (PPCI) results in lower mortality than fibrinolytic therapy in patients with myocardial infarction. We investigated which categories of patients with myocardial infarction would benefit most from the strategy of PPCI and, thus, have lowest numbers needed to treat to prevent a death. Methods: Individual patient data were obtained from 22 (n = 6,763) randomized trials evaluating efficacy and safety of PPCI versus fibrinolysis. A risk score was developed and validated to estimate the probability of 30-day death in individuals. Patients were then divided in quartiles according to risk. Subsequent analyses were performed to evaluate if the treatment effect was modified by estimated risk. Results: Overall, 446 patients (6.6%) died within 30 days after randomization. The mortality risk score contained clinical characteristics, including the time from symptom onset to randomization. The c-index was 0.76, and the Hosmer-Lemeshow test was nonsignificant, reflecting adequate discrimination and calibration. Patients randomized to PPCI had lower mortality than did patients randomized to fibrinolysis (5.3% vs 7.9%, adjusted odds ratio 0.63, 95% CI 0.42-0.84, P < .001). The interaction between risk score and allocated treatment interaction term had no significant contribution (P = .52) to the model, indicating that the relative mortality reduction by PPCI was similar at all levels of estimated risk. In contrast, the absolute risk reduction was strongly related to estimated risk at baseline: the numbers needed to treat to prevent a death by PPCI versus fibrinolysis was 516 in the lowest quartile of estimated risk compared with only 17 in the highest quartile. Conclusion: Primary percutaneous coronary intervention is consistently associated with a strong relative reduction in 30-day mortality, irrespective of patient baseline risk, and should therefore be considered as the first choice reperfusion strategy whenever feasible. If access to percutaneous coronary intervention is >2 hours, fibrinolysis remains a legitimate option in low-risk patients because of the small absolute risk reduction by PPCI in this particular cohort. [Copyright &y& Elsevier]

Although a fibrinolytic pharmacoinvasive strategy is recommended for patients with ST elevation myocardial infarction (STEMI) unable to undergo timely primary percutaneous coronary intervention (PCI), there are limited data addressing outcomes specific to those with successful or unsuccessful pharmacologic reperfusions. Accordingly, we evaluated a contemporary pharmacoinvasive strategy for failed and successful reperfusions within the STrategic Reperfusion Early After Myocardial infarction study. Of 1,823 per-protocol-treated patients with STEMI, we examined clinical outcomes and angiographic and electrocardiographic metrics in 3 groups as follows: fibrinolysis requiring rescue (rescue, n = 348), fibrinolysis with scheduled angiography (scheduled, n = 516), and primary PCI (n = 927). Compared with pharmacoinvasive patients undergoing scheduled angiography, rescue patients were more likely to have anterior wall myocardial infarction, more baseline ST-segment elevation and deviation, as well as Q waves in the distribution of their ST elevation. Residual ST elevation ⩾2 mm 30 minutes after angiography occurred in 27.9%, 7.9%, and 24.8% of patients who underwent rescue, scheduled, and primary PCI, respectively. Thirty-day composite event rates (all-cause death, cardiogenic shock, heart failure, and reinfarction) were 18.7%, 5.5%, and 13.9%; all-cause death: 6.1%, 2.1%, and 3.9%; cardiogenic shock: 7.5%, 2.0%, and 5.4%; heart failure: 11.8%, 2.3%, and 7.6%; and reinfarction: 1.5%, 1.4%, and 2.2%, for rescue, scheduled, and primary PCI, respectively. Compared with successfully reperfused patients undergoing scheduled angiography, the adjusted relative risk of the primary outcome was 2.92 (95% confidence interval 1.92 to 4.45) in rescue patients. In conclusion, pharmacoinvasive-treated patients requiring rescue angiography had greater baseline risk with more co-morbidities and worse 30-day outcomes compared with successful fibrinolytic-treated patients. Residual ST elevation after reperfusion assists in defining prognosis. [ABSTRACT FROM AUTHOR]

Q waves have been shown to be a stronger prognostic marker than time from symptom onset to percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction. We examined whether the relative importance of these 2 measurements is modulated by patient gender. Q waves in the area of ST-segment elevation on baseline electrocardiogram were evaluated at a central core laboratory in 4,530 patients with ST-segment elevation myocardial infarction (3,468 men and 1,062 women) without previous infarction and who underwent PCI in the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. Women were older and had higher rates of diabetes, hypertension, Killip class >I, and lower creatinine clearance compared to men. Time from symptom onset to PCI >3 hours was associated with a trend toward worse 90-day mortality (adjusted hazard ratio 1.5, 95% confidence interval 0.9 to 2.2) in men but not in women (0.8, 0.5 to 1.4). In contrast, presence of Q waves on baseline electrocardiogram was associated with significantly higher 90-day mortality in men (adjusted hazard ratio 1.7, 95% confidence interval 1.0 to 2.7) and women (2.3, 1.2 to 4.2). In conclusion, in this gender-specific analysis, baseline Q wave was found be a better marker of risk of 90-day mortality than time from symptom onset to PCI, overall, and especially in women. [Copyright &y& Elsevier]

The prognostic value of myocardial infarct size estimation by QRS scoring in patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI) is unclear. The standard 32-point Selvester QRS score on the discharge electrocardiogram (each point ∼3% left ventricular mass) was calculated in 4,113 patients with STEMI who underwent primary PCI and survived to hospital discharge in the APEX-AMI trial. QRS scores were divided into tertiles, i.e., ≤3 (<10% myocardium), 4 to 7 (10% to 21% myocardium), and ≥8 (>21% myocardium). Adjusted associations between QRS score and 90-day outcomes (death and composite of death/congestive heart failure (CHF)/shock) were examined. Higher QRS scores were associated with male gender, higher heart rate, worse Killip class, noninferior infarct location, greater ST-segment deviation, and longer times to reperfusion. Higher QRS scores were also associated with impaired culprit artery flow before and after PCI and more frequent multivessel disease. Adverse outcomes occurred more often in patients with higher QRS scores (90-day death: 1.9%, QRS score 0 to 3; 3.4%, 4 to 7; 4.9%, ≥8; 90-day death/shock/CHF: 4.5%, 0–3; 7.8%, 4 to 7; 12.1%, ≥8). After multivariable adjustment, patients with higher QRS scores remained more likely to develop an adverse outcome versus those with QRS scores ≤3 (score 4 to 7, hazard ratios [HR] for death 2.08, 95% confidence interval [CI] 1.26 to 3.41; HR for death/CHF/shock 2.00, 95% CI 1.26 to 3.17; score ≥8, HR for death 2.57, 95% CI 1.56 to 4.24, HR for death/CHF/shock 2.93, 95% CI 1.84 to 4.67). In conclusion, infarct size as estimated by QRS scoring at hospital discharge is an independent and prognostically relevant metric in patients with STEMI undergoing primary PCI. [ABSTRACT FROM AUTHOR]