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BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that may emerge from overlapping systemic processes associated with comorbidities. We assessed whether unique clusters of circulating proteins are associated with specific clinical characteristics and functional status at baseline and follow-up in a well-phenotyped cohort of patients with HFpEF. METHODS: We evaluated 368 proteins associated with cardiovascular disease and inflammation in prerandomization blood samples from 763 VITALITY-HFpEF (Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With HFpEF) participants who had a left ventricular ejection fraction ≥45% and a heart failure decompensation event within 6 months. Proteins were clustered, and their associations with clinical characteristics, baseline, and 24-week functional outcomes (Kansas City Cardiomyopathy Questionnaire Physical Limitation Score, 6-minute walk distance [6MWD], and Fried frailty phenotype) were estimated with linear regression. Elastic net regression was used to derive a proteomic summary composite to predict changes in 24-week functional outcomes. RESULTS: Four unique protein clusters were identified, containing 24, 66, 197, and 81 proteins. At baseline, 2 protein clusters with the hub proteins caspase-3 and Dickkopf-related protein 1 were associated with increased frailty, whereas the cluster with tumor necrosis factor receptor 1 as a hub protein was associated with lower Kansas City Cardiomyopathy Questionnaire Physical Limitation Score and shorter 6MWD. By contrast, the cluster with protein C as a hub protein was associated with less frailty and longer a 6MWD. The 24-week increase in 6MWD was negatively correlated with the protein cluster with caspase-3; the protein C cluster was correlated with less frailty at 24 weeks. The baseline proteomic summary composite predicted observed changes in Kansas City Cardiomyopathy Questionnaire Physical Limitation Score and 6MWD at 24 weeks (r=0.42 and 0.30; P<0.001 for both). CONCLUSIONS: Proteomics differentiate specific baseline functional traits associated with HFpEF and may facilitate phenotyping in a heterogeneous disease. These proteins also provide insights into the diverse pathophysiology of HFpEF and which patients may improve functional status during follow-up. [ABSTRACT FROM AUTHOR]

BACKGROUND: Selecting high-risk patients with heart failure with potentially modifiable cardiovascular events is a priority. Our objective was to evaluate NT-proBNP (N-terminal pro-B-type natriuretic peptide) changes during a 30-day screening to establish (1) the frequency and direction of changes; (2) whether a relationship exists between changes in NT-proBNP and the primary composite outcome of cardiovascular death and heart failure hospitalization; and (3) whether changes in NTproBNP relate to vericiguat's clinical benefit. METHODS: VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) randomized 5050 patients with heart failure with reduced ejection fraction and a recent worsening heart failure event. We studied 3821 patients who had NT-proBNP measured during screening and at randomization. RESULTS: Sixteen hundred exhibited a >20% reduction, 1412 had =20% change, and 809 showed a >20% rise in NT-proBNP levels. As compared with the primary composite outcome of 28.4/100 patient-years (497 events; 31.1%) in patients with a >20% decline in NT-proBNP, those with >20% during screening had worse outcomes; 48.8/100 patient-years (359 events; 44.4%); adjusted hazard ratio, 1.61 (95% CI, 1.39-1.85). Those patients with a =20% change in NT-proBNP had intermediate outcomes; 39.2/100 patient-years (564 events; 39.9%); adjusted hazard ratio, 1.33 (95% CI, 1.17-1.51). No relationship existed between NT-proBNP changes during screening and vericiguat's effect on cardiovascular death and heart failure hospitalization. CONCLUSIONS: Substantial differences occurred in the rates of cardiovascular death and heart failure hospitalization, especially in patients with a >20% change in NT-proBNP levels during screening interval. Sequential NT-proBNP levels add important prognostic information meriting consideration in future heart failure trials. [ABSTRACT FROM AUTHOR]

BACKGROUND: We examined whether the primary composite outcome (cardiovascular death or heart failure hospitalization) was related to differences in background use and dosing of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), a randomized trial of vericiguat versus placebo. METHODS: We evaluated the adherence to guideline use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. We assessed basic adherence; indication-corrected adherence accounting for guideline indications and contraindications; and dosecorrected adherence (indication-corrected adherence+=50% of drug dose target). Associations between study treatment and the primary composite outcome according to the adherence to guidelines were assessed using multivariable adjustment; adjusted hazard ratios with 95% CIs and Pinteraction are reported. RESULTS: Of 5050 patients, 5040 (99.8%) had medication data at baseline. For angiotensin-converting enzyme inhibitor, angiotensin-receptor blockers, and angiotensin receptor-neprilysin inhibitors, basic adherence to guidelines was 87.4%, indication-corrected was 95.7%, and dose-corrected was 50.9%. For beta-blockers, basic adherence was 93.1%, indicationcorrected was 96.2%, and dose-corrected was 45.4%. For mineralocorticoid receptor antagonists, basic adherence was 70.3%, indication-corrected was 87.1%, and dose-corrected was 82.2%. For triple therapy (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or angiotensin receptor-neprilysin inhibitors+beta-blocker+mineralocorticoid receptor antagonist), basic adherence was 59.7%, indication-corrected was 83.3%, and dose-corrected was 25.5%. Using basic or dose-corrected adherence, the treatment effect of vericiguat was consistent across adherence to guidelines groups, with or without multivariable adjustment with no treatment heterogeneity. CONCLUSIONS: Patients in VICTORIA were well treated with heart failure with reduced ejection fraction medications. The efficacy of vericiguat was consistent across background therapy with very high adherence to guidelines accounting for patient-level indications, contraindications, and tolerance. [ABSTRACT FROM AUTHOR]

• 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]

BACKGROUND: Randomized controlled trials (RCTs) often target enrollment of patients with demographics and outcomes less representative of the broader population of interest. To provide context for the VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction), we designed a registry of hospitalized patients with worsening heart failure to characterize their clinical profile, outcomes, and reasons for their nonparticipation in a RCT. METHODS: Fifty-one RCT sites in Canada and the United States participated. Eligible patients included those with chronic heart failure, hospitalized for heart failure, and an ejection fraction <45%; no other exclusions were applied. Sites identified patients between 2017 and 2019 during the RCT enrollment period. RCT eligibility criteria were applied, and non-mutually exclusive reasons for nonenrollment were captured. Mortality at 1 year was estimated via the Meta-Analysis Global Group in Chronic Heart Failure risk score or as observed in the RCT. RESULTS: Overall, 2056 patients were enrolled in the registry; 61% (n=1256) were ineligible for the RCT, 37% (n=766) were eligible but not enrolled, and 2% (n=34) were also enrolled in the RCT. Registry participants had a median age of 70, 33% were women, and 63% were White. The median risk score predicted a 20.9% 1-year mortality, higher than in the RCT (predicted 14.7% and observed 11.5%). Major reasons for ineligibility in the RCT included the use of nitrates (23%), systolic blood pressure <100 mm Hg (12%), and substance use (11%) with other exclusion criteria <10%. For eligible patients, reasons for nonparticipation in the RCT included lack of interest in participating (28%), poor compliance (25%), inability to complete follow-up (23%), too sick (20%), unable to provide consent (17%), and distance from site (15%). CONCLUSIONS: Patients with worsening heart failure in routine clinical practice exhibit high-risk features, and approximately one-third were eligible for an RCT but excluded. The majority of these nonparticipating patients had modifiable reasons. [ABSTRACT FROM AUTHOR]

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]

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]

The article discusses the health condition known as acute heart failure. It explores the nature of the condition by characterizing its clinical features, practice patterns as well as in-hospital results of acute heart failure patients. According to the authors, in-hospital mortality was higher compared with patients who usually participate in randomized clinical trials.

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]

Background: 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. Method: TIMI flow grade of the infarct-related artery was assessed before and after PCI by visual estimation of local investigators (LI) and by an independent core laboratory (CL). We evaluated agreement between the CL and LI and the relationship between post-PCI TIMI flow grade and 90-day outcomes (mortality; death/congestive heart failure/shock). Results: Of 922 patients with independent CL estimation of TIMI flow grade, there was moderate agreement in the pre-PCI assessment (κ = 0.56) and poor agreement post-PCI (κ = 0.36); moreover, these disparities were directionally different before versus after PCI. Disagreement between LI and CL occurred in 167 patients pre-PCI (19%) and in 123 (14%) patients post-PCI. LI TIMI grades consistently underestimated flow pre-PCI in 63% and overestimated flow post-PCI in 78% of patients relative to the CL. Core laboratory estimation of post-PCI TIMI flow grade provided better prediction of 90-day mortality and death/congestive heart failure/shock than that of LI. Conclusion: Significant quantitative and directional variation existed in TIMI flow grades assessed by LI versus a CL in nearly a fifth of the patients. Core laboratory interpretation post-PCI provides better prediction of clinical outcomes. These data deserve consideration when interpreting angiographic data from STEMI patients without CL estimation. [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: 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. Methods: All patients with ACS in Alberta, Canada, between April 1, 1999, and March 31, 2001, were included. Prodromes reported during all physician visits in the 90 days before ACS presentation consisted of (1) pain (chest, arm, shoulder, neck, jaw, throat, or leg); (2) anxiety/fatigue; (3) gastrointestinal disturbances; (4) head-related conditions (dizziness, headache, visual disturbances); and (5) other (sweating, shortness of breath, heart racing, cough, numbness). Results: Of 14,230 patients with ACS, 2,268 (15.9%, 45.6% women) sought medical attention for at least one prodrome, with pain and anxiety/fatigue most common. Prodromes were associated with increased cardiac investigations before ACS in both sexes. After adjustment for baseline characteristics, a significant interaction between sex and prodromes was found (P [interaction] = .011). Prodromes were associated with improved 1-year survival in women (adjusted hazard ratio [HR] 0.74, 95% CI 0.58-0.95, P = .016, risk-adjusted mortality 8.7% vs 11.1% [without prodromes], P < .001) but not in men (adjusted hazard ratio 0.92, 95% CI 0.76-1.12, P = .422, 9.9% [with prodromes] vs 9.1% [without prodromes], P = .358). Conclusions: A small proportion of patients with ACS seek medical attention for prodromal symptoms in the 90 days before ACS. Seeking help for these symptoms is associated with improved survival in women but not in men. [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]