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Background Galectin-3 is a soluble ß-galactoside-binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results HF-ACTION was a randomized controlled trial of exercise training in patients with chronic heart failure due to left ventricular (LV) systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher NYHA class, lower systolic blood pressure, higher creatinine, higher NTproBNP, and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio = 1.14 per 3 ng/mL increase in galectin-3, P<0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Conclusions Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP.

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In a retrospective pooled analysis of 8 clinical trials, obstructive non-IRA disease was common among patients presenting with STEMI, and was associated with a modest statistically significant increase in 30-day mortality. These findings require confirmation in prospectively designed studies, but raise questions about the appropriateness and timing of non-IRA revascularization in patients with STEMI.

Objectives To compare the prognostic efficacy of 6MW and CPX tests in stable outpatients with chronic HF. Background Cardiopulmonary exercise (CPX) and 6 minute walk (6MW) tests are commonly applied as prognostic gauges for systolic heart failure (HF) patients, but few direct comparisons have been conducted. Methods Stable NYHA class II and III systolic HF patients (ejection fraction ≤35%) from Heart Failure: A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) were studied. 6MW distance (6MWD) and CPX indices (peak oxygen consumption [VO2] and minute ventilation-carbon dioxide production [VE/VCO2] slope) were compared as predictors of all-cause mortality/hospitalization and all-cause mortality over 2.5 years mean follow-up. Results 2,054 HF-ACTION participants underwent both CPX and 6MW tests at baseline (median age 59 years; 71% male; 64% NYHA class II and 36% NYHA class III). In unadjusted models and in models that included key clinical and demographic covariates, C-indices of 6MWD were 0.58 and 0.65 (unadjusted) and 0.62 and 0.72 (adjusted) in predicting all-cause mortality/ hospitalization and all-cause mortality, respectively. C-indices for peak VO2 were 0.61 and 0.68 (unadjusted) and 0.63 and 0.73 (adjusted). C-indices for VE/VCO2 slope were C=0.56 and 0.65 (unadjusted) and 0.61 and 0.71 (adjusted); combining peak VO2 and VE/VCO2 slope did not improve C-indices. Overlapping 95% confidence intervals and modest integrated discrimination improvement values confirmed similar prognostic discrimination by 6MWD and CPX indices within adjusted models. Conclusion In systolic HF outpatients 6MWD and CPX indices demonstrated similar utility as univariate predictors for all-cause hospitalization/mortality and all-cause mortality. However, 6MWD or CPX indices added only modest prognostic discrimination to models that included important demographic and clinical covariates.

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The available results from these three trials do not provide credible evidence of any adverse effect of ezetimibe on rates of cancer. Follow-up of longer duration will permit the balance of risks and benefits to be determined more reliably.

on behalf of the Platelet Inhibition and Patient Outcomes (PLATO) Trial InvestigatorsBackground-The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. Methods and Results-We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (nϭ6539) compared with those not on a PPI (nϭ12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04 -1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79 -1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14 -1.49). Conclusions-The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events. Clinical Trial Registration-http://www.clinicaltrials.gov. Unique identifier: NCT00391872. Key Words: acute coronary syndrome Ⅲ clopidogrel Ⅲ mortality Ⅲ myocardial infarction Ⅲ ticagrelor I n patients with both ST-segment and non-ST-segment elevation acute coronary syndromes (ACS), current clinical practice guidelines recommend the use of dual antiplatelet therapy with acetylsalicylic acid and P2Y12 inhibition. 1,2 Conflicting data exist regarding the potential adverse interaction between the effects on clinical events of the P2Y12 inhibitor clopidogrel and proton pump inhibitors (PPIs), whereas the importance of such an interaction with other P2Y12 inhibitors is less investigated. Clinical Perspective on p 986Several pharmacodynamic studies have shown that some PPIs reduce the inhibition of platelet aggregation achieved with clopidogrel treatment. [3][4][5][6][7][8][9][10] This phenomenon seems meContinuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. ). Relevant exclusions to trial participation included an increased risk of bleeding (eg, active bleeding, major surgery Յ30 days), clinically im...