Come e quando è nato BRAVEHEART
L’idea di formare un gruppo di lavoro che si interessasse del “cuore impavido” degli anziani e, specificamente del ruolo dei betabloccanti nella terapia dell’insufficienza cardiaca è nata nel corso di un incontro tra ricercatori nell’ambito di un Congresso Nazionale di Cardiologia nel Maggio 2002.
Il presupposto fondamentale era la carenza di dati attendibili sull’efficacia e sulla sicurezza dei farmaci betabloccanti in soggetti di età avanzata, anche a causa della esclusione degli stessi (in particolare se donne) dai grandi studi clinici randomizzati. L’idea di base è stata la progettazione e la conduzione di rigorosi studi osservazionali finalizzati a produrre evidenze dai e per i pazienti del “mondo reale” della pratica clinica quotidiana.
Un ruolo non secondario è stato svolto anche dalla comune percezione della necessità di dare una risposta efficace ai crescenti bisogni di salute della popolazione anziana affetta da malattie cardiovascolari.
Infine, questo gruppo di studio nasce dall’aggregazione spontanea dei suoi componenti e compie le sue ricerche in assoluta indipendenza di programmi da altri organismi privati o pubblici.
Da chi è composto il gruppo di studio?
Il nucleo di ricerca di BRAVEHEART è composto da:
– Giovanni Cioffi, Casa di Cura Villa Bianca, Trento
– Cristina Opasich, Fondazione Salvatore Maugeri, Pavia
– Stefania De Feo, Fondazione Salvatore Maugeri, Pavia
– Luigi Tarantini, Ospedale S.Martino, Belluno
– Donatella Del Sindaco, IRCCS INRCA, Roma
– Giovanni Pulignano, Ospedale S.Camillo, Roma
– Andrea Di Lenarda, Ospedali Riuniti, Trieste.
Produzione scientifica
Pubblicazioni In Riviste INDEXED peer-reviewed
- Tarantini L, Cioffi G, Pulignano G, Del Sindaco D, Aspromontes N, Valle R, Di Tano G, Misuraca G, Clemenza F, Di Lenarda A.
Heart failure in primary care in Italy: analysis of management and needs by general practitioners
G Ital Cardiol (Rome). 2010 Sep;11(9):680-7 >Abstract disponibile< - Del Sindaco D, Tinti MD, Monzo L, Pulignano G.
Clinical and economic aspects of the use of nebivolol in the treatment of elderly patients with heart failure.
Clin Interv Aging. 2010 Dec 3;5:381-93 >Abstract disponibile< - Cioffi G, Gerdts E, Cramariuc D, Tarantini L, Di Lenarda A, Pulignano G, Sindaco DD, Stefenelli C, de Simone G.
Left atrial size and force in patients with systolic chronic heart failure: Comparison with healthy controls and different cardiac diseases.
Exp Clin Cardiol. 2010 Fall;15(3):e45-51. >Abstract disponibile< - Del Sindaco D, Pulignano G, Cioffi G, Tarantini L, Di Lenarda A, De Feo S, Opasich C, Minardi G, Giovannini E, Leggio F.
Safety and efficacy of carvedilol in very elderly diabetic patients with heart failure.
J Cardiovasc Med (Hagerstown). 2007 Sep;8(9):675-82. >Abstract disponibile< - Cioffi G, Tarantini L, Pulignano G, Del Sindaco D, De Feo S, Opasich C, Dilenarda A, Stefenelli C, Furlanello F. Prevalence, predictors and prognostic value of acute impairment in renal function during intensive unloading therapy in a community population hospitalized for decompensated heart failure. J Cardiovasc Med (Hagerstown). 2007 Jun;8(6):419-27. >Abstract disponibile<
- Del Sindaco D, Pulignano G, Minardi G, Apostoli A, Guerrieri L, Rotoloni M, Petri G, Fabrizi L, Caroselli A, Venusti R, Chiantera A, Giulivi A, Giovannini E, Leggio F.
Two-year outcome of a prospective, controlled study of a disease management programme for elderly patients with heart failure.
J Cardiovasc Med (Hagerstown). 2007 May;8(5):324-9. >Abstract disponibile< - G. Pulignano, D. Del Sindaco, A. Di Lenarda, G. Sinagra.
The evolving care for elderly with heart failure: from the “high tech” to the “high touch” approach.
J Cardiovasc Med (Hagerstown). 2006 Dec;7(12):841-6. No abstract available. >Abstract disponibile< - G.Cioffi, S.De Feo, G.Pulignano, D.Del Sindaco, L.Tarantini, C.Stefenelli, C.Opasich.
Does atrial fibrillation in very elderly patients with chronic systolic heart failure limit the use of carvedilol?
Int J Cardiol. 2006 Feb 15; 107(2):220-4. >Abstract disponibile< - G.Cioffi, L.Tarantini, S.De Feo, G.Pulignano, D.Del Sindaco, C.Stefenelli, C.Opasich.
Pharmacological left ventricular reverse remodeling in elderly patients receiving optimal therapy for chronic heart failure.
Eur Heart J Fail. 2005 Oct; 7(6):1040-8. >Abstract disponibile< - G.Cioffi, L.Tarantini, S.De Feo, G.Pulignano, D.Del Sindaco, C.Stefenelli, A.Di Lenarda, C.Opasich.
Functional mitral regurgitation predicts 1-year mortality in elderly patients with systolic chronic heart failure.
Eur Heart J Fail. 2005 Dec; 7(7):1112-7. >Abstract disponibile< - C.Opasich, S.De Feo, G.Cioffi, G.Pulignano, D.Del Sindaco, L.Tarantini, A.Gualco, A.Patrignani.
Does atrial fibrillation in elderly patients with chronic heart failure limit the efficacy of carvedilol? Suggestions from an observational study.
Ital Heart J. 2005 Apr; 6(4):323-7. >Abstract disponibile< - G.Cioffi, L.Tarantini, S.De Feo, G.Pulignano, D.Del Sindaco, C.Stefenelli, C.Opasich.
Pharmacological Left Ventricular Reverse Remodeling in Elderly Patients with Chronic Heart Failure.
Eur J Heart Failure 2004 - G.Cioffi, L.Tarantini, S.De Feo, G.Pulignano, D.Del Sindaco, C.Stefenelli, C.Opasich.
Dilated vs Non-dilated Cardiomyopathy in Elderly.Population Treated with Guideline-Based Medical Therapy for Systolic Chronic Heart Failure.
Journal of Cardiac failure 2004: 10: 481-48. - L.Tarantini, G.Cioffi, C.Opasich, A.Di Lenarda, G.Pulignano, D.Del Sindaco, S.De Feo, C.Stefenelli, P.Russo, G.Catania.
Pre-discharge Initiation of Beta-Blocker Therapy in Elderly Patients hospitalized for Acute Decompensation of Chronic Heart Failure: An Effective Strategy to Implement Beta-blockade in Heart Failure.
Italian Heart Journal 2004: 5.
Abstracts a congressi nazionali
- G.Cioffi, L.Tarantini, G.Pulignano, D.Del Sindaco, S.De Feo, C.Stefenelli, A.Di Lenarda, C.Opasich.
Prognostic value of mitral regurgitation in the elderly patients with systolic chronic heart failure.
Ital Heart J 2004; 5: suppl 5:149S. - G.Pulignano, D.Del Sindaco, R.Valle, N.Aspromonte, G.Misuraca, L.Tarantini, G.Cioffi, A.Di Lenarda.
La pratica del beta-blocco nello scompenso cardiaco dalla prospettiva dei medici di base: osservazioni su un campione multicentrico.
Ital Heart J 2004; 5: suppl 5:132S. - L.Tarantini, G.Misuraca, G.Pulignano, N.Aspromonte, D.Del Sindaco, R.Valle, G.Cioffi, A.Di Lenarda.
Come formulano la diagnosi di scompenso cardiaco i medici di medicina generale?
Ital Heart J 2004; 5: suppl 5:132S. - G.Cioffi, S.De Feo, G.Pulignano, D.Del Sindaco, L.Tarantini, C.Stefenelli, C.Opasich.
Does atrial fibrillation in elderly patients with chronic heart failure limit the use of carvedilol?
Ital Heart J 2004; 5 (abstr Supplement): in press. - G.Cioffi, L.Tarantini, S.De Feo, G.Pulignano, D.Del Sindaco, C.Stefanelli, C.Opasich.
Mitral regurgitation in Elderly Population with systolic chronic heart failure predicts 1-year mortality, not hospitalization for clinical decompensation .
Ital Heart J 2004; 5 (abstr Supplement): in press.
Pre-discharge initiation of beta-blocker therapy in elderly patients hospitalized for acute decompensation of chronic heart failure: an effective strategy for the implementation of beta-blockade in heart failure.
Tarantini L, Cioffi G, Opasich C, Di Lenarda A, Pulignano G, Del Sindaco D, De Feo S, Stefenelli C, Russo P, Catania G.
Ital Heart J. 2004 Jun;5(6):441-9.
BACKGROUND: Current guidelines recommend beta-blockers in patients with heart failure and left ventricular systolic dysfunction. These agents, however, are largely underused in elderly patients because of the perception of up-titration complexity and the fear of side effects.
METHODS: We prospectively assessed the feasibility, safety, tolerability, and 1-year outcome of the in-hospital initiation of carvedilol in elderly patients admitted for worsening heart failure.
RESULTS: Among 164 eligible subjects (age > 70 years, left ventricular ejection fraction < 40% and no sign of congestion), 120 (73%) received carvedilol, on average 4.5 days after admission. The drug was permanently withdrawn in 10 out of 116 survivors (9%) at 60 days: 5 did not tolerate the starting dose because of worsening heart failure (n = 1), bradycardia (n = 1), and bronchospasm (n = 3). Two discontinued carvedilol during the in-hospital dose titration phase because of increasing premature ventricular beats and transient second degree atrioventricular block. The remaining 3 dropouts (fatigue in 2 and symptomatic bradycardia in 1 case) occurred after discharge. During the period between 60 days and 12 months, carvedilol was discontinued in 2 patients because of a depressive syndrome and symptomatic bradycardia. In no case these adverse events lead to death or were life-threatening, required hospitalization or resulted in any disability. The 1-year tolerability was 89%, the mortality was 17.5%, the frequency of hospitalization for worsening heart failure was 21%.
CONCLUSIONS: Thus, our results show that the in-hospital initiation of carvedilol is feasible and well-tolerated in elderly patients with recent worsening heart failure, and allows rapid identification of the most intolerant patients. The proportion of subjects taking carvedilol after 1 year from discharge was very high. This unconventional approach could significantly modify the use of beta-blockers in clinical practice.
Pharmacological left ventricular reverse remodeling in elderly patients receiving optimal therapy for chronic heart failure.
Cioffi G, Tarantini L, De Feo S, Pulignano G, Del Sindaco D, Stefenelli C, Opasich C.
Eur J Heart Fail. 2005 Oct;7(6):1040-8.
BACKGROUND AND AIMS: In recent years, reversal of established left ventricular (LV) dilatation has been increasingly recognized in middle-aged patients with dilated cardiomyopathy receiving angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers. We performed this prospective study to evaluate whether optimized therapy for heart failure also induces LV reverse remodeling in older patients.
METHODS: One hundred and twenty-four patients aged >70 years with LV ejection fraction <40% underwent clinical and echocardiographic evaluation at baseline and after 1 year. During the early stage of follow-up, pharmacological therapy was optimized. LV reverse remodeling was defined as a reduction in LV end-diastolic volume >25% from baseline to final evaluation.
RESULTS: LV reverse remodeling was recognized in 32 patients (26%). Compared to the subjects who did not improve LV geometry, those with reverse remodeling had, at baseline, higher arterial blood pressure, lower serum creatinine levels, shorter duration of symptoms of heart failure, more frequently received beta-blocker therapy and had predominantly nonischemic aetiology. The variables associated with the development of reverse remodeling in the multivariate analysis were shorter duration of symptoms of heart failure (Odds ratio: 7.7; CI: 2.5-23.3, p=0.0001) and beta-blocker therapy (Odds ratio: 6.0; CI: 1.6-23.3, p=0.01).
CONCLUSIONS: LV reverse remodeling takes place in elderly as well as in younger heart failure patients. A significant proportion of elderly patients undergoes this favourable process which occurs prevalently in patients receiving beta-blocker therapy with a short history of cardiac disease.
Dilated versus nondilated cardiomyopathy in the elderly population treated with guideline-based medical therapy for systolic chronic heart failure.
Cioffi G, Tarantini L, De Feo S, Pulignano G, Del Sindaco D, Stefenelli C, Opasich C.
J Card Fail. 2004 Dec;10(6):481-9.
BACKGROUND: Although the process by which the left ventricular (LV) remodels in response to an injury generally leads to dilatation, in patients with heart failure (HF) the recognition of a small or mildly dilated left ventricle is not uncommon. We investigated the prevalence and the characteristics of elderly patients with traditional dilated and nondilated cardiomyopathy (CMP). We also assessed the response to the guideline-based medical therapy and the prognosis based on LV dilatation in this population.
METHODS AND RESULTS: We selected 243 patients >70 years of age with HF and LV ejection fraction <40% who underwent clinical and echocardiographic evaluations at baseline and after 12 months. They were subdivided into 2 groups according to baseline LV end-diastolic volume (LVEDV) (values < or =78 mL/m(2) identified nondilated CMP). Nondilated CMP was recognized in 64 patients (26%) who showed at baseline better clinical status, less severe mitral regurgitation, and higher LV ejection fraction than those with dilated CMP. At the final evaluation, favorable changes in clinical and echocardiographic parameters could be detected in both groups. The magnitude of these variations did not differ between the groups. The risk of hospitalization for worsening HF was 2.4-fold higher in patients with nondilated than dilated CMP. Mortality was 11% and 20%, respectively (P = .06). Statistical analysis revealed a direct, approximately linear relationship between LVEDV and outcomes in this population.
CONCLUSIONS: A total of 1 of 4 elderly patients with systolic HF had a nondilated left ventricle. These patients had a better clinical presentation than did counterparts with dilated left ventricles. After HF therapy is optimized, the likelihood of improvement is independent of LV size in this population, whereas the risk of death or worsening HF linearly increases with LV dilatation.
Functional mitral regurgitation predicts 1-year mortality in elderly patients with systolic chronic heart failure.
Cioffi G, Tarantini L, De Feo S, Pulignano G, Del Sindaco D, Stefenelli C, Di Lenarda A, Opasich C.
Eur J Heart Fail. 2005 Dec;7(7):1112-7.
BACKGROUND AND AIM: Mitral regurgitation (MR) has been demonstrated to be a powerful predictor of adverse outcome in middle-aged patients with chronic heart failure (CHF). In this study, we sought to define the prognostic impact of functional mitral regurgitation in a population of elderly patients with systolic CHF.
METHODS: One hundred seventy-five outpatients aged >70 years with validated CHF and left ventricular ejection fraction <40% underwent clinical and echocardiographic evaluations at baseline. Mitral regurgitation was diagnosed by Color Doppler and quantified in 5 categorical values using a 0-4+ grading system. Outcome measures included 1-year mortality and hospitalization for worsening CHF.
RESULTS: The distribution of patients according to the 5 different degrees of MR detected at baseline was: absent=11%, 1+=31%, 2+=38%, 3+=16%, 4+=4%. The relationship between MR and mortality was direct and approximately linear (r=0.39, p=0.00001). The prevalence of death in the 5 subgroups was 0%, 7%, 15%, 45%, 57%, respectively. Multivariate logistic regression analysis showed that MR was the strongest predictor of death (OR 4.47, 95% CI 1.50-13.0), independently of the presence of diabetes mellitus, older age and larger left ventricular end-diastolic volume. No association was found between MR and hospitalization for worsening CHF (r=0.08, p=0.41).
CONCLUSIONS: This study establishes the direct and independent relationship between MR severity and one-year mortality among elders with systolic CHF. Conversely, MR does not provide useful information regarding the risk of subsequent hospitalization for worsening CHF.
Does atrial fibrillation in elderly patients with chronic heart failure limit the efficacy of carvedilol? Suggestions from an observational study.
Opasich C, De Feo S, Cioffi G, Pulignano G, Del Sindaco D, Tarantini L, Gualco A, Patrignani A.
Ital Heart J. 2005 Apr;6(4):323-7.
BACKGROUND: No clinical investigation provided any information about a possible influence of atrial fibrillation on the response to beta-blocker therapy in elderly patients with chronic heart failure (CHF). The aim of this study was to observe carvedilol effects in a cohort of patients > 70 years of age with CHF due to left ventricular dysfunction and with chronic atrial fibrillation.
METHODS: An observational, 12-month prospective clinical and echocardiographic study was carried out on 240 patients > 70 years of age with heart failure due to systolic dysfunction, 64 of whom with atrial fibrillation.
RESULTS: After 1 year of beta-blocker treatment, patients with atrial fibrillation and those in sinus rhythm showed similar benefits, in terms of symptomatic improvement (deltaNYHA -0.44 if atrial fibrillation vs -0.57 if sinus rhythm, p = NS), reduction of events (death + hospitalizations -38 vs -15%), recovery of cardiac function (left ventricular ejection fraction delta +8.8 vs +9.4%, p = NS; left ventricular end-diastolic volume delta -17.2 vs -12.5 ml, p = NS), and reduction in mitral regurgitation (delta -042 vs -0.57, p = NS). No difference was found between the two study groups regarding left ventricular end-diastolic volume reduction (12% in atrial fibrillation patients and 18% in sinus rhythm patients, p = NS) and prevalence of the “reverse remodeling” phenomenon (22 and 21%, respectively, p = NS).
CONCLUSIONS: In CHF patients > 70 years of age, beta-adrenergic blockade was shown to be equally effective in improving symptoms and left ventricular geometry and function in patients with atrial fibrillation or in sinus rhythm, without any adjunctive sign of long-term clinical deterioration.
Does atrial fibrillation in very elderly patients with chronic systolic heart failure limit the use of carvedilol?
Cioffi G, De Feo S, Pulignano G, Del Sindaco D, Tarantini L, Stefenelli C, Opasich C.
Int J Cardiol. 2006 Feb 15;107(2):220-4.
BACKGROUND AND AIMS: It is well known that beta-blockers are useful in patients with chronic heart failure (CHF). These favourable effects have recently been observed even in elderly CHF patients. Objectives of the present study were to evaluate the feasibility, tolerability and safety of carvedilol therapy in a cohort of patients > 70 years of age with CHF and left ventricular ejection fraction < 40% with chronic atrial fibrillation. For this purpose, we designed an observational, 12-month prospective study.
RESULTS: Among 240 patients who were referred to our centers and met inclusion criteria, 64 had chronic atrial fibrillation (27%). Thirty-nine out of these 64 subjects (61%) were treated with carvedilol, while 25 patients (39%) had contraindications to such treatment. In the cohort of 176 patients with stable sinus rhythm (control group), carvedilol could be administered in 121 patients (69%), while it was not given in 55 (31%, p=ns). Airways disease was the main reason for exclusion from carvedilol in this setting of patients. No difference in 1-year tolerability of study drug was observed among patients with chronic atrial fibrillation (29 of 33 patients=87.9%) and stable sinus rhythm (95 of 102=93.1%). Adverse events leading to the discontinuation of carvedilol in these two populations were rare and never resulted in any disability, death or were life-threatening.
CONCLUSION: In over-70 patients with systolic CHF, chronic atrial fibrillation does not limit the possibility of testing beta-blocker therapy. Carvedilol was equally tolerated and safe in patients with atrial fibrillation and sinus rhythm.
Safety and efficacy of carvedilol in very elderly diabetic patients with heart failure.
Del Sindaco D, Pulignano G, Cioffi G, Tarantini L, Di Lenarda A, De Feo S, Opasich C, Minardi G, Giovannini E, Leggio F.
J Cardiovasc Med (Hagerstown). 2007 Sep;8(9):675-82.
OBJECTIVE: Beta-blockers are often cautiously prescribed to older heart failure diabetics because of the paucity of published data and their perceived unfavourable effects on glucose metabolism, in spite of the evidence of their effectiveness and safety in middle-aged diabetic patients. The aim of this study was to compare the safety, tolerability and efficacy of long-term administration of carvedilol in a group of elderly patients with chronic heart failure, with and without concomitant diabetes.
METHODS: Two hundred and fifty-two patients aged > or =70 years with heart failure and left ventricular ejection fraction < or =40% were followed in specialised heart failure clinics. Diabetes was present in 29.7%. Carvedilol was associated with conventional optimised treatment in 64% of diabetics and 65% of non-diabetics (P = NS).
RESULTS: At baseline, diabetics presented with a longer duration of symptoms, higher Charlson comorbidity index, more frequent renal dysfunction and smaller left ventricular volumes than non-diabetics. New York Heart Association functional class and ejection fraction were similar in the two groups. At 1-year follow-up, tolerability (93.7 vs. 92.2%) and mean daily dose (24 +/- 17 vs. 23 +/- 14 mg/day) of carvedilol were similar in diabetics and non-diabetics. No worsening of fasting glucose, glycosylated haemoglobin and creatinine levels as well as the incidence of deaths and hospitalisations was observed in diabetics treated with carvedilol. Similar improvements in New York Heart Association class and mitral regurgitation severity were observed in diabetic and non-diabetic patients taking carvedilol. Ejection fraction showed a significant improvement, more pronounced in non-diabetics than in diabetics (+10 vs. +7 points; improvement of at least 10 points: 15 vs. 36%, P = 0.03).
CONCLUSIONS: Similarly to younger ones, also in older patients, diabetes does not negatively influence the safety, tolerability and efficacy of carvedilol. However, diabetes remains a strong prognostic factor limiting the reversibility of left ventricular systolic dysfunction and the effect of treatment on subsequent outcome. PMID: 17700396 [PubMed – indexed for MEDLINE]
Abstracts a congressi internazionali
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