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Background Implantable cardioverter defibrillator (ICD) is recommended in patients (pts) with non-ischaemic heart failure with left ventricular systolic dysfunction who receive optimal medical therapy (OMT) in order to prevent sudden cardiac death (SCD). However, the results of the DANISH study have recently shown the limits of these recommendations. It is therefore mandatory to reconsider the risk stratification of SCD in this population. Purpose The purpose of our study is to determine independent predictors of severe arrhythmic events (AE in pts with non-ischemic systolic heart failure. Methods Between January 1998 and December 2014, all consecutive outpatients with non-ischemic systolic heart failure, receiving OMT and without a history of significant arrhythmic events, were included. We performed to all the pts a clinical and biological evaluation, an echocardiography, a cardiopulmonary exercise test, a radionuclide angiography and a Holter-ECG. Follow-up was performed either by direct examination, by contact with the general practitioner or the cardiologist and by remote monitoring if available. The composite primary endpoint was the occurrence of SCD, recovered cardiac arrest, sustained ventricular tachycardia, or appropriate therapy by the ICD. Results We included 910 pts with a mean age of 53±12 years, 244 (27%) were women, LVEF was 36±10%. Most of the pts received renin-angiotensin blockers (97%) and betablockers (84%), 77% received diuretics and 41% spironolactone. During a median follow-up period of 6.33 [3.29–10.18] years, 160 (17.6%) pts presented the composite primary endpoint. The median time between the assessment and the occurrence of AE was 4.05 [1.68–7.85] years. The most powerful independent predictor of AE was non-sustained ventricular tachycardia (≥3 ectopic beats) (HR: 2.8 [1.66–4.72], p Conclusion LVEF is not the most powerful predictor of severe arrhythmic events in outpatients with non-ischemic systolic heart failure receiving optimal medical therapy. New risk scores are required. We found that in addition to LVEF, gender, QRS duration, sinus rhythm, left atrial diameter and more particularly non-sustained ventricular tachycardia were independent predictors of AE. This score needs to be validated in an independent population. Acknowledgement/Funding None

Aims Following myocardial infarction (MI), both age and left ventricular (LV) remodelling are associated with an increased risk of adverse events. We tested the hypothesis that the increased incidence of heart failure following MI in elderly patients is associated with a greater propensity for LV remodelling. Methods and results We monitored 266 patients with anterior MI. Echocardiographic studies were performed at hospital discharge, at 3 months, and at 1 year following hospitalization for MI. A clinical follow-up examination was performed after 3 years. Left ventricular remodelling was documented by an increase in LV end-diastolic volume after 1 year. Left ventricular end-diastolic and end-systolic volumes did not differ with age for all time points studied. Left ventricular remodelling was observed in 31, 26, 34, and 34% of patients 71 years of age, respectively. The 3 year heart-failure hospitalization rates were 1.9, 1.5, 11.0, and 20.3% for patients 71 years of age, respectively. Hospitalization for heart failure was more frequent in older patients. Conclusion We found that age was a major determinant of subsequent re-hospitalization for heart failure. However, we found no significant association between age and the LV remodelling process.

To determine the potential adjunct of high-sensitivity (hs) C-reactive protein for risk stratification in patients with stable congestive heart failure (CHF).We studied 546 consecutive patients clinically stable with an ejection fraction45% who were referred to our centre for evaluation of left ventricular dysfunction. hs C-reactive protein levels were determined on blood samples obtained on entry into the study. Clinical follow-up (median 972 days) was obtained for 545 patients. Cardiovascular mortality was significantly increased (P=0.001) in patients with hs C-reactive protein3 mg/L. By multivariable analysis, including clinical, biological, and echocardiographic variables, hs C-reactive protein3 mg/L was an independent predictor of cardiovascular mortality [HR=1.78 (1.17-2.72); P=0.008]; the strongest predictive parameter in this model was B-type natriuretic peptide (BNP) (P=0.005). When peak VO(2) was included into the model, hs C-reactive protein3 mg/L remained an independent predictor of cardiovascular mortality [HR=1.55 (1.02-2.38); P=0.04]; the strongest predictive parameter in this model was peak VO(2) (P0.0001). In patients with ischaemic CHF, cardiovascular mortality was significantly increased in patients with hs C-reactive protein3 mg/L (P=0.001), whereas in patients with non-ischaemic CHF, hs C-reactive protein3 mg/L was not associated with cardiovascular mortality (P=0.098). By multivariable analysis, hs C-reactive protein3 mg/L was an independent predictor of cardiovascular mortality in ischaemic patients [HR=2.16 (1.23-3.78)] but not in non-ischaemic patients [HR=1.05 (0.52-2.11)].Cardiovascular mortality is increased in CHF patients with hs C-reactive protein3 mg/L. The impact of hs C-reactive protein is independent of usual prognostic parameters, in particular BNP and peak VO(2). The interest of hs C-reactive protein determination appears to be especially marked in patients with ischaemic cardiomyopathy.

Aims To test the hypothesis that diabetic status may be used as a prognostic indicator in heart failure (HF) patients. Methods and results We studied 1246 consecutive patients with left ventricular dysfunction. All patients had a cardiopulmonary exercise test and an echocardiogram. Cardiac catheterisation was systematically performed to define HF aetiology. Twenty-two percent of the patients were diabetic (hypoglycaemic drugs or fasting blood glucose \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(>\) \end{document}126 mg/dL); in diabetic patients, HF aetiology was ischaemic in 58% vs. 40% in non-diabetic patients (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p{

Aims Previous studies have demonstrated that the radionuclide right ventricular (RV) ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE), and tissue Doppler peak systolic tricuspid annular velocity (STr) were independent predictors of cardiac survival in stable patients with left ventricular systolic dysfunction (LVSD). No study has compared the prognostic value of these three RV parameters. The aim of this study was to compare the prognostic value of RVEF, TAPSE, and STr in a large group of patients with LVSD. Methods and results We analysed 527 consecutive patients who underwent an extensive prognostic evaluation (clinical data, biological data, radionuclide angiography, echoDopplercardiography, cardiopulmonary exercise test). Tricuspid annular plane systolic excursion and STr were weakly correlated with RVEF (r = 0.20). During a follow-up period of 1268 days (802-1830), there were 121 cardiovascular deaths. Best cut-off values were 37%, 9.7 cm/s, and 18.5 mm for RVEF, STr, and TAPSE, respectively. Right ventricular ejection fraction was a powerful independent predictor of cardiac survival [relative risk (RR): 2.05 (1.29-3.26), P = 0.002]. Peak systolic tricuspid annular velocity added a modest prognostic information [RR: 1.56 (1.02-2.39), P = 0.04]. However, the combination of STr with RVEF was the most powerful predictor of cardiovascular death. Tricuspid annular plane systolic excursion was not an independent predictor of cardiac survival. Conclusions Right ventricular systolic function remains a powerful independent predictor of the clinical outcome. Even in the context of a complete echocardiographic assessment, radionuclide RVEF continues to be the most powerful RV systolic parameter for cardiac survival prediction. However, the determination of STr, in addition to RVEF, could improve risk stratification.

Aims Chronic heart failure following myocardial infarction (MI) is characterized by progressive left ventricular remodelling (LVR). Despite significant improvements in MI management, LVR remains a frequent complication. Although several risk factors have been identified, such as infarct size, LVR is difficult to predict in clinical practice. Methods and results Using a rat model of MI and phosphoproteomic technology, we discovered that remodelling is associated with decreased levels of myocardial and plasma serine208-phosphorylated troponin T (TnT). To confirm the association in human plasma, we developed new specific polyclonal antibodies against human/rat serine207/208-phosphorylated TnT and tested plasma obtained in the first week after MI from patients with low, intermediate, and high remodelling a year later. We observed a significant decrease of serine207-phosphorylated TnT and of the serine207-phosphorylated TnT/total TnT ratio in those with intermediate or high LVR. These differences remained statistically significant when adjusted for other determinants of LVR. In contrast, baseline B-type natriuretic peptide levels were not associated with LVR. Conclusion The level of circulating phosphorylated TnT could be a new biomarker of LVR.

Stress hyperglycaemia (SH) is associated with adverse outcome in patients with acute myocardial infarction (MI) but the mechanisms underlying this association are unknown. Our hypothesis was that SH on admission for acute MI may be associated with left ventricular (LV) remodelling.We analysed LV remodelling in 162 non-diabetic patients with anterior MI. SH was defined as a glycaemia on admissionor=7 mmol/L. Systematic echocardiographic follow-up was performed at 3 months and 1 year after MI. The changes in end-diastolic volume (EDV) and end-systolic volume (ESV) from baseline to 1 year were 11.4 +/- 16.5 and 6.4 +/- 12.4 ml/m(2), respectively, in patients with SH vs. 1.9 +/- 11.1 and 0.2 +/- 8.5 ml/m(2), respectively, in patients without SH (both P0.0001). When LV remodelling was defined as a20% increase in EDV, it was observed in 46% patients in the SH group vs. 19% patients in the no SH group (P = 0.0008). By multivariable analysis, baseline wall motion score index (P = 0.001) and SH (P = 0.009) were independently associated with changes in EDV. SH was an independent predictor of LV remodelling [adjusted OR: 3.22 (1.31-7.94)].SH is a major and independent predictor of LV remodelling after anterior MI in non-diabetic patients.

Aims Functional mitral regurgitation (MR) and myocardial asynchronism occur commonly in patients with dilated cardiomyopathy and affect adversely their prognosis and symptoms. The aim of this study was to evaluate the mechanisms of changes in MR severity during dynamic exercise in patients with chronic heart failure (CHF). Methods and results Seventy patients with CHF due to left ventricular (LV) systolic dysfunction [LV ejection fraction (EF)

Aims To assess the possible effect of functional polymorphisms in matrix metalloproteinase (MMP) gene promoters on the clinical outcome of patients with heart failure. Methods and results We studied 444 consecutive patients who were referred to our centre for evaluation of left ventricular dysfunction. We extracted genomic DNA from white blood cells and determined the −1306 C\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(>\) \end{document}T MMP-2, −1171 5A\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(>\) \end{document}6A MMP-3, and −1562 C\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(>\) \end{document}T MMP-9 polymorphisms. Clinical follow-up (median 717 days) was obtained for 443 patients. The MMP-3 polymorphism had a different impact on cardiac survival in HF patients with ischaemic and non-ischaemic cardiomyopathy (interaction \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p{