GVM Hospitals of Care and Research

Villa Santa Maria, Italy

GVM Hospitals of Care and Research

Villa Santa Maria, Italy
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Latini R.,Instituto Of Ricerche Farmacologiche Mario Negri | Gullestad L.,University of Oslo | Masson S.,Instituto Of Ricerche Farmacologiche Mario Negri | Nymo S.H.,Rikshospitalet | And 13 more authors.
European Journal of Heart Failure | Year: 2012

Aims Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF. Methods and resultsPlasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C-reactive protein (hsCRP), and N-terminal pro brain natriuretic peptide (NT-proBNP). PTX3 concentration [median (Q1Q3) 5.34 (3.557.64) ng/mL, n 2690] was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [759 events, hazard ratio (HR) for 1 SD increase 1.20, 95 confidence interval (CI) 1.121.30, P < 0.0001], cardiovascular mortality (587 events, HR 1.27, 95 CI 1.171.38, P < 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95 CI 1.121.30, P < 0.0001), and marginally improved discrimination. Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3.ConclusionIn two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation.Trial registrationNCT00336336 (GISSI-HF), NCT00206310 (CORONA). © 2012 The Author.

Harjola V.-P.,University of Helsinki | Follath F.,University of Zürich | Nieminen M.S.,University of Helsinki | Brutsaert D.,University of Antwerp | And 8 more authors.
European Journal of Heart Failure | Year: 2010

AimsAcute heart failure (AHF) has a poor prognosis. We evaluated 3-and 12-month mortality in different clinical classes of AHF patients from 30 European countries who were included in the EuroHeart Failure Survey (EHFS) II.Methods and resultsFollow-up data were available for 2981 AHF patients, of these 62 had a history of chronic HF. One-year mortality after discharge was lower in patients with de novo AHF when compared with acutely decompensated chronic HF (ADCHF), 16.4 vs. 23.2 (P < 0.001). Cardiogenic shock conferred the highest cumulative 1-year mortality (52.9) as a result of in-hospital mortality of 39.3. Long-term prognosis in decompensated AHF was also dismal. Hypertensive HF was associated with the lowest mortality (13.7 at 1 year). Age, prior myocardial infarction, creatinine level, and low plasma sodium were independently associated with mortality during the whole follow-up period. Diabetes, anaemia, and history of chronic HF were associated with worse and hypertension with better long-term survival. History of cerebrovascular disease was associated with worse short-term outcome.ConclusionEarly and late mortality differ between de novo AHF and ADCHF and between clinical classes of AHF. EHFS II identifies clinical risk markers and demonstrates the importance of a thorough characterization of AHF populations according to history and clinical presentation.

Tavazzi L.,GVM Hospitals of Care and Research | Senni M.,Papa Giovanni XXIII Hospital | Metra M.,University of Brescia | Gorini M.,Research Center | And 6 more authors.
Circulation: Heart Failure | Year: 2013

Background.Clinical observational studies on heart failure (HF) deal mostly with hospitalized patients, few with chronic outpatients, all with no or limited longitudinal observation. Methods and Results.This is a multicenter, nationwide, prospective observational trial on a population of 5610 patients, 1855 hospitalized for acute HF (AHF) and 3755 outpatients with chronic HF (CHF), followed up for 1 year. The cumulative total mortality rate at 1 year was 24% in AHF (19.2% in 797 patients with de novo HF and 27.7% in 1058 with worsening HF) and 5.9% in CHF. Cardiovascular deaths accounted for 73.1% and 65.3% and HF deaths for 42.4% and 40.5% of total deaths in AHF and CHF patients, respectively. One-year hospitalization rates were 30.7% in AHF and 22.7% in CHF patients. Among the independent predictors of 1-year all-cause death, age, low systolic blood pressure, anemia, and renal dysfunction were identified in both acute and chronic patients. A few additional variables were significant only in AHF (signs of cerebral hypoperfusion, low serum sodium, chronic obstructive pulmonary disease, and acute pulmonary edema), whereas others were observed only in CHF patients (lower body mass index, higher heart rate, New York Heart Association class, large QRS, and severe mitral regurgitation). Conclusions.In this contemporary data set, patients with CHF had a relatively low mortality rate compared with those with AHF. Rates of adverse outcomes in patients admitted for AHF remain very high either in-hospital or after discharge. Most deaths were cardiovascular in origin and .40% of deaths were directly related to HF. © 2013 American Heart Association, Inc.

Cowie M.R.,Imperial College London | Cure S.,I3 Innovus | Bianic F.,I3 Innovus | McGuire A.,LSE Health and Social Car | And 2 more authors.
European Journal of Heart Failure | Year: 2011

Aims: A recent randomized placebo-controlled clinical trial has reported reductions in mortality and hospitalizations in patients with chronic heart failure (CHF) who were prescribed highly purified omega-3 polyunsaturated fatty acid ethyl esters (n-3 PUFA). This study aimed at evaluating the cost and benefits associated with their use in the treatment of CHF in a UK setting.Methods and resultsResults from a recent clinical trial were used to develop a Markov model to project clinical outcomes while capturing relevant costs and patient quality of life. The model captured outcomes over a lifetime horizon from a UK National Health Service perspective, with direct costs accounted in 2009 GBP (£) and discounted at 3.5 together with clinical benefits. Results are presented in terms of life expectancy, quality-adjusted life expectancy, direct costs, and incremental cost-effectiveness ratios. In addition to standard therapy, n-3 PUFA vs. placebo increased lifetime direct costs by £993 (≈€1150), with additional quality-adjusted life expectancy of 0.079 quality-adjusted life years (QALYs), and mean lifetime costs of £12 636 (≈€14 600) per QALY gained. Probabilistic sensitivity analyses suggested a 60 likelihood of n-3 PUFA being regarded as cost-effective versus placebo at a willingness-to-pay threshold of £30 000 (≈€34 600) per QALY gained.ConclusionsBy currently accepted standards of value for money in the UK; the addition of n-3 PUFA to optimal medical therapy for patients with heart failure is likely to be cost-effective. © 2011 The Author.

Ferrari R.,University of Ferrara | Beltrami C.A.,University of Udine | Tavazzi L.,GVM Hospitals of Care and Research
Cardiovascular and Hematological Disorders - Drug Targets | Year: 2010

The crucial role played by the endothelium in cardiovascular disorders has been repetitively recognised. Endothelium injury has been implicated in atherosclerosis, thrombosis, hypertension and other cardiovascular diseases. Recently, however, research has undertaken a new avenue. As mature endothelial cells posses limited regenerative capacities, the interest has been switched to the circulating endothelial progenitor cells (EPCs). Indeed, the scientific community has made progress in understanding the role of EPCs in the maintenance of endothelial integrity and function as well as post natal neovascularisation. It has been suggested that these cells are able to home in the site of heart injury / damage and that they might take part in angiogenesis, giving hope for new treatment opportunities. There is evidence that reduced availability of EPCs or impairment of their function is associated with more severe CV disease and to comorbid risk factors. Different current drug regimes are able to influence bone marrow production and release of EPCs and several growth factors are considered for possible useful new therapeutic approaches. Thus, many studies into the potential use of EPCs in the clinical setting have recently been conducted with conflicting results. The goal of this review article is to discuss current therapies to regenerate new vessels and therefore to enhance myocardial function. The article overviews the search strategy and the pathophysiological aspects behind this therapy, consider the target currently under investigation and set the stage for new ideas. © 2010 Bentham Science Publishers Ltd.

Macchia A.,Consorzio Mario Negri Sud | Marchioli R.,Consorzio Mario Negri Sud | Tognoni G.,Consorzio Mario Negri Sud | Scarano M.,Consorzio Mario Negri Sud | And 3 more authors.
American Heart Journal | Year: 2010

Background: In a previous metaanalysis on the approved treatments for pulmonary hypertension, we reported that all therapies caused small changes in 6-minute walk distance over a short period, with minimal effects on hemodynamics and no effect on survival. Since that last review, 10 new clinical trials with about 1,500 patients have been published, which has increased the statistical power of our observations. Methods: A systematic review of all clinical trials in pulmonary arterial hypertension was done. Results: The pooled effect of all treatments strategies (relative risk [95% CI], P) now shows a significant reduction of 39% (2%-62%, P = .041) in all-cause mortality. The benefits were confined only to patients with advanced disease for 16 weeks, regardless of which class of drug is used. When considering the effects within each drug family, no class of drug produced a statistically significant reduction in all-cause mortality. The improved survival bore no relationship with the change in 6-minute walk, the primary end point in most of the trials. Conclusions: The impact of vasodilators on long-term survival in pulmonary arterial hypertension remains uncertain. Future trials need to (a) adopt new trial designs that can better address clinical benefits, (b) use new end points that incorporate our best understanding of the disease rather than the ones that are easy to administer, and (c) include longer durations of study and other strategies to clarify if survival is affected. © 2010 Mosby, Inc. All rights reserved.

Masson S.,Instituto Mario Negri | Anand I.,University of Minnesota | Favero C.,Instituto Mario Negri | Barlera S.,Instituto Mario Negri | And 7 more authors.
Circulation | Year: 2012

Background - Cardiac troponins are emerging as important prognostic markers in chronic cardiovascular conditions like stable coronary artery disease or chronic heart failure (HF). Less is known about the relation between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and future events in HF. We determined the association between changes over time in hs-cTnT and outcome in patients with chronic HF. Methods and Results - We analyzed 5284 patients with chronic HF from 2 independent randomized clinical trials, the Valsartan Heart Failure Trial (Val-HeFT) (n=4053) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial (n=1231). hs-cTnT was measured at randomization and after 3 months (GISSI-HF) or 4 months of follow-up (Val-HeFT). The association between changes over time of hs-cTnT and various outcomes was tested in multivariable models. In both studies, increases in hs-cTnT levels over time were associated with age, diabetes mellitus, worsening of renal function (reduction in estimated glomerular filtration rate), and baseline and increases in N-terminal pro-brain natriuretic peptide concentrations. Increases in hs-cTnT concentrations were associated with all-cause mortality (incidence rates, 8.19 [7.51-8.88] and 6.79 [5.98-7.61] per 100 person-years in Val-HeFT and GISSI-HF, respectively, with hazard ratios [95% confidence intervals] of 1.59 [1.39-1.82] and 1.88 [1.50-2.35]) after adjustment for conventional risk factors and baseline levels of hs-cTnT and N-terminal pro-brain natriuretic peptide. Changes in hs-cTnT concentration modestly improved prognostic discrimination beyond baseline values for fatal outcomes only. Conclusions - Despite very low circulating concentrations, changes in hs-cTnT concentrations over time are robust predictors of future cardiovascular events in patients with chronic HF but add limited prognostic discrimination. © 2011 American Heart Association, Inc.

Oliva F.,Niguarda Hospital | Oliva F.,Outcome Coordinating Center | Mortara A.,Policlinico di Monza | Cacciatore G.,San Giovanni Addolorata Hospital | And 7 more authors.
European Journal of Heart Failure | Year: 2012

Aims Registries and surveys improve knowledge of the 'real world'. This paper Aims to describe baseline clinical profiles, management strategies, and the in-hospital outcome of patients admitted to hospital for an acute heart failure (AHF) episode.Methods and resultsIN-HF Outcome is a nationwide, prospective, multicentre, observational study conducted in 61 Cardiology Centres in Italy. Up to December 2009, 5610 patients had been enrolled, 1855 (33) with AHF and 3755 (67) with chronic heart failure (CHF). Baseline and in-hospital outcome data of AHF patients are presented. Mean age was 72 ± 12 years, and 39.8 were female. Hospital admission was due to new-onset heart failure (HF) in 43 of cases. Co-morbid conditions were observed more frequently in the worsening HF group, while those with de novo HF showed a higher heart rate, blood pressure, and more preserved left ventricular ejection fraction (LVEF). Electrical devices were previously implanted in 13.3 of the entire group. Inotropes were administered in 19.4 of the patients. The median duration of hospital stay was 10 days (interquartile range 7-15). All-cause in-hospital death was 6.4, similar in worsening and de novo HF. Older age, hypotension, cardiogenic shock, pulmonary oedema, symptoms of hypoperfusion, hyponatraemia, and elevated creatinine were independent predictors of all-cause death.ConclusionOur registry confirms that in-hospital mortality in AHF is still high, with a long length of stay. Pharmacological treatment seems to be practically unchanged in the last decades, and the adherence to HF guidelines concerning implantable cardioverter defibrillators/cardiac resynchronization therapy is still very low. Some AHF phenotypes are characterized by worst prognosis and need specific research projects. © 2012 The Author.

Swedberg K.,Gothenburg University | Komajda M.,University Pierre and Marie Curie | Bohm M.,Universitatskliniken des Saarlandes | Borer J.S.,New York University | And 2 more authors.
European Journal of Heart Failure | Year: 2010

Aims: Elevated heart rate is a significant marker for mortality and morbidity in cardiovascular disease including heart failure. Despite background treatment with a beta-blocker, many patients with heart failure and low ejection fraction maintain a heart rate above 70 b.p.m. Ivabradine reduces heart rate directly through inhibition of the If ionic current.MethodsSHIFT is a randomized, double-blind study designed to compare ivabradine with placebo on outcomes in patients with symptomatic chronic heart failure (NYHA class II-IV), left-ventricular ejection fraction ≤35, and a prior hospitalization for worsening heart failure within the previous 12 months. Randomized treatment is given on top of guidelines-based therapy for chronic heart failure, including a beta-blocker at optimized dose. Resting heart rate at baseline must be ≥70 b.p.m. The primary endpoint is the composite of the time to first event of cardiovascular death or hospitalization for worsening heart failure. Secondary endpoints include all-cause, cardiovascular and heart failure mortality, and hospitalization. The randomized treatment period lasts approximately 12-48 months. The study will include approximately 6500 patients and will continue until ≥1600 primary endpoints have occurred. The first patient was randomized in October 2006, and the study is expected to end in 2010.ConclusionThe SHIFT study will assess if a heart rate reduction by direct sinus node inhibition can reduce cardiovascular outcomes in patients with chronic heart failure and left-ventricular systolic dysfunction.

Mozaffarian D.,Brigham and Women's Hospital | Mozaffarian D.,Harvard University | Marchioli R.,Consorzio Mario Negri Sud | Marchioli R.,Laboratory of Clinical Epidemiology of Cardiovascular Disease | And 10 more authors.
JAMA - Journal of the American Medical Association | Year: 2012

Context: Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results. Objective: To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF. Design, Setting, and Patients: The Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Intervention: Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first. Main Outcome Measure: Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. Results: At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P=.74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P=.70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P=.73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events. Conclusion: In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF. Trial Registration: clinicaltrials.gov Identifier: NCT00970489. ©2012 American Medical Association. All rights reserved.

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