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Aims Evaluation of predictors of silent coronary artery disease (SCAD) in high-risk asymptomatic diabetic patients and to evaluate their two-year outcome. Methods and results Four hundred diabetic patients without prior CAD but at high CAD risk underwent myocardial perfusion scintigraphy (MPS) in this prospective multicentre outcome trial. MPS were abnormal in 22% of patients. Male sex (OR 2.223, 1.152–4.290; p = 0.017), diabetes duration (OR 1.049,1.015–1.085; p = 0·005), peripheral artery disease (OR 2.134, 1·150–3.961; p = 0.016), smoking (OR 2.064, 1.109–3.839; p = 0·022), systolic blood pressure (OR 1.014, 1.00–1.03, p = 0·056), brain natriuretic peptide (OR 1.002, 1.001–1.004, p = 0·005) independently predicted an abnormal MPS: if < 2 and > 3 predictors were present, 3.2% and 47% patients had an abnormal MPS, respectively (p < 0·001). Two-year major adverse cardiac event rates increased from 2·9% to 14·6%, cardiac death rates from 0·6% to 4·1% in patients with summed stress scores ≤ 10 and > 10%, respectively (each p < 0.045). Conclusions Male sex, diabetes duration, peripheral artery disease, smoking, elevated systolic blood pressure and increased brain-natriuretic peptides independently predicted SCAD. In presence of > 3 predictors, almost 50% of patients had an abnormal MPS. They may benefit from screening by MPS since the extent of the MPS abnormality discriminated clearly between a favourable compared to a bad 2-year outcome. However, even highest risk patients without objective evidence of CAD had a benign prognosis without need for specific evaluation or therapy. Trial Registration Number: ISRCTN87953632. [ABSTRACT FROM AUTHOR]

Background Cardiac remodeling and its reversibility are key in HF outcomes. The ST2-R2 score was recently developed to predict relevant left ventricular (LV) reverse remodeling (R2) in patients with heart failure (HF). In the present study we sought to validate the ST2-R2 score for grading improvement in LV ejection fraction (EF) and LV size at one year, and to evaluate its prognostic implication up to 4 years. Methods A total of 569 patients with baseline LVEF < 40% from three international cohorts (Barcelona, TIME-CHF, and PROTECT) were included in the study. Patients were classified into four strata based on their ST2-R2 score, which took into account concentrations of the biomarker ST2, non-ischemic etiology, absence of left bundle branch block, HF duration, baseline LVEF, and β-blocker treatment. Results A significant relationship was observed between ST2-R2 scores and changes in LVEF and indexed LV sizes. LVEF recovery (from + 5.6% to + 17.3%; p < 0.001), percentage reduction in LV end-systolic volume index (from − 6.1% to − 32.1%; p < 0.001) and in LV end-systolic diameter index (from − 1.1% to − 18.6%; p < 0.001) increased over the ST2-R2 strata. A similar trend was observed with diastolic parameters. Improvement in LV function and size was inversely predictive of mortality. Hazard ratios for risk of death, using the lower ST2-R2 score strata (< 9) as a reference, were 0.49 (p < 0.001; score 9–11), 0.27 (p < 0.001; score 12–14), and 0.17 (p < 0.001; score 15–17). Conclusions The ST2-R2 score predicts reverse LV remodeling in HF patients and is useful for predicting mortality up to 4 years. [ABSTRACT FROM AUTHOR]

Aims Renal failure is a major challenge in treating heart failure ( HF) patients. HF medication may deteriorate renal function, but the impact thereof on outcome is unknown. We investigated the effects of HF medication on worsening renal function ( WRF) and the relationship to outcome. Methods and results This post-hoc analysis of TIME-CHF ( NT-proBNP-guided vs. symptom-guided management in chronic HF) included patients with LVEF ≤45% and ≥1 follow-up visit ( n = 462). WRF III was defined as a rise in serum creatinine ≥0.5 mg/ dL (i.e. 44.2 µmol/L) at any time during the first 6 months. Four classes of medication were considered: loop diuretics, beta-blockers, renin-angiotensin system ( RAS)-blockers, and spironolactone. Functional principal component analysis of daily doses was used to comprehend medication over time. All-cause mortality after 18 months was the primary outcome. Interactions between WRF, medication, and outcome were tested. Patients with WRF III received on average higher loop diuretic doses ( P = 0.0002) and more spironolactone ( P = 0.02), whereas beta-blockers ( P = 0.69) did not differ and lower doses of RAS-blockers were given ( P = 0.09). There were significant interactions between WRF III, medicationn and outcome. Thus, WRF III was associated with poor prognosis if high loop diuretic doses were given ( P = 0.001), but not with low doses ( P = 0.29). The opposite was found for spironolactone (poor prognosis in the case of WRF III with no spironolactone, P <0.0001; but not with spironolactone, P = 0.31). Beta-blockers were protective in all patients ( P <0.001), but most in those with WRF III ( P <0.05 for interaction). RAS-blockade was associated with improved outcome ( P = 0.006), irrespective of WRF III. Conclusion Based on this analysis, it may be hypothesized that high doses of loop diuretics might have detrimental effects, particularly in combination with significant WRF, whereas spironolactone and beta-blockers might be protective in patients with WRF. [ABSTRACT FROM AUTHOR]