Socio-economic factors determine maternal and neonatal outcomes in women with peripartum cardiomyopathy: A study of the ESC EORP PPCM registry.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a global disease with substantial morbidity and mortality. The aim of this study was to analyze to what extent socioeconomic factors were associated with maternal and neonatal outcomes. METHODS: In 2011, >100 national and affiliated member cardiac societies of the European Society of Cardiology (ESC) were contacted to contribute to a global PPCM registry, under the auspices of the ESC EORP Programme. We investigated the characteristics and outcomes of women with PPCM and their babies according to individual and country-level sociodemographic factors (Gini index coefficient [GINI index], health expenditure [HE] and human developmental index [HDI]). RESULTS: 739 women from 49 countries (Europe [33%], Africa [29%], Asia-Pacific [15%], Middle East [22%]) were enrolled. Low HDI was associated with greater left ventricular (LV) dilatation at time of diagnosis. However, baseline LV ejection fraction did not differ according to sociodemographic factors. Countries with low HE prescribed guideline-directed heart failure therapy less frequently. Six-month mortality was higher in countries with low HE; and LV non-recovery in those with low HDI, low HE and lower levels of education. Maternal outcome (death, re-hospitalization, or persistent LV dysfunction) was independently associated with income. Neonatal death was significantly more common in countries with low HE and low HDI, but was not influenced by maternal income or education attainment. CONCLUSIONS: Maternal and neonatal outcomes depend on country-specific socioeconomic characteristics. Attempts should therefore be made to allocate adequate resources to health and education, to improve maternal and fetal outcomes in PPCM.

EURObservational Research Programme: a bibliometric assessment of its scientific output.

AIMS: Given the lack of reliable observational data, a network of volunteer centres, and standardized methodological procedures, the European Society of Cardiology EURObservational Research Programme (EORP) was set up to provide a better understanding of real-world cardiovascular care and outcomes. We aimed to evaluate the scientific impact of EORP using a bibliometric approach. METHODS AND RESULTS: We collected data for each individual publication and for each individual journal with at least one EORP publication. Bibliometric indicators evaluating research performance were categorized into those evaluating EORP publications (publication-based indicators) and those assessing the journals where those papers were published (journal-based indicators). During the first ∼11 years since its inception, we found that EORP produced 189 publications, with most published in journals in the first quartile (60.9%) or the second quartile (33.5%) of the Web of Science Journal Citation Report. The total number of citations to EORP publications was 9630 (average citation per publication of 51, h-index of 54, and 29 EORP publications with ≥100 citations). Of EORP publications, 20 had an Altmetric Attention Score >50 and 9 had a score >100. A total of 52 EORP papers have been cited 65 times in ESC Clinical Practice Guidelines between 2013 and 2021. CONCLUSION: EORP registries have contributed to impactful scientific knowledge. The high-quality metrics highlight the relevance of the EORP international cardiovascular registries to the academic community. Efforts are needed to support this, and other programmes aimed at delivering real-world evidence from independent patient data of cardiovascular care and outcomes across multiple geographies.

[ANMCO Position paper: Reorganization of cardiology in the era of the COVID-19 pandemic]. / Position paper ANMCO: Riorganizzazione della cardiologia in epoca di pandemia COVID-19.

The COVID-19 pandemic represents an unprecedented event that has brought deep changes in hospital facilities with reshaping of the health system organization, revealing inadequacies of current hospital and local health systems. When the COVID-19 emergency will end, further evaluation of the national health system, new organization of acute wards, and a further evolution of the entire health system will be needed to improve care during the chronic phase of disease. Therefore, new standards for healthcare personnel, more efficient organization of hospital facilities for patients with acute illnesses, improvement of technological approaches, and better integration between hospital and territorial services should be pursued. With experience derived from the COVID-19 pandemic, new models, paradigms, interventional approaches, values and priorities should be suggested and implemented.

Physicians' guideline adherence is associated with long-term heart failure mortality in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry.

BACKGROUND: Physicians' adherence to guideline-recommended therapy is associated with short-term clinical outcomes in heart failure (HF) with reduced ejection fraction (HFrEF). However, its impact on longer-term outcomes is poorly documented. Here, we present results from the 18-month follow-up of the QUALIFY registry. METHODS AND RESULTS: Data at 18 months were available for 6118 ambulatory HFrEF patients from this international prospective observational survey. Adherence was measured as a continuous variable, ranging from 0 to 1, and was assessed for five classes of recommended HF medications and dosages. Most deaths were cardiovascular (CV) (228/394) and HF-related (191/394) and the same was true for unplanned hospitalizations (1175 CV and 861 HF-related hospitalizations, out of a total of 1541). According to univariable analysis, CV and HF deaths were significantly associated with physician adherence to guidelines. In multivariable analysis, HF death was associated with adherence level [subdistribution hazard ratio (SHR) 0.93, 95% confidence interval (CI) 0.87-0.99 per 0.1 unit adherence level increase; P = 0.034] as was composite of HF hospitalization or CV death (SHR 0.97, 95% CI 0.94-0.99 per 0.1 unit adherence level increase; P = 0.043), whereas unplanned all-cause, CV or HF hospitalizations were not (all-cause: SHR 0.99, 95% CI 0.9-1.02; CV: SHR 0.98, 95% CI 0.96-1.01; and HF: SHR 0.99, 95% CI 0.96-1.02 per 0.1 unit change in adherence score; P = 0.52, P = 0.2, and P = 0.4, respectively). CONCLUSION: These results suggest that physicians' adherence to guideline-recommended HF therapies is associated with improved outcomes in HFrEF. Practical strategies should be established to improve physicians' adherence to guidelines.

Clinical characteristics of patients from the worldwide registry on peripartum cardiomyopathy (PPCM): EURObservational Research Programme in conjunction with the Heart Failure Association of the European Society of Cardiology Study Group on PPCM.

AIMS: The purpose of this study is to describe disease presentation, co-morbidities, diagnosis and initial therapeutic management of patients with peripartum cardiomyopathy (PPCM) living in countries belonging to the European Society of Cardiology (ESC) vs. non-ESC countries. METHODS AND RESULTS: Out of 500 patients with PPCM entered by 31 March 2016, we report on data of the first 411 patients with completed case record forms (from 43 countries) entered into this ongoing registry. There were marked differences in socio-demographic parameters such as Human Development Index, GINI index on inequality, and Health Expenditure in PPCM patients from ESC vs. non-ESC countries (P < 0.001 each). Ethnicity was Caucasian (34%), Black African (25.8%), Asian (21.8%), and Middle Eastern backgrounds (16.4%). Despite the huge disparities in socio-demographic factors and ethnic backgrounds, baseline characteristics are remarkably similar. Drug therapy initiated post-partum included ACE inhibitors/ARBs and mineralocorticoid receptor antagonists with identical frequencies in ESC vs. non-ESC countries. However, in non-ESC countries, there was significantly less use of beta-blockers (70.3% vs. 91.9%) and ivabradine (1.4% vs. 17.1%), but more use of diuretics (91.3% vs. 68.8%), digoxin (37.0% vs. 18.0%), and bromocriptine (32.6% vs. 7.1%) (P < 0.001). More patients in non-ESC vs. ESC countries continued to have symptomatic heart failure after 1 month (92.3% vs. 81.3%, P < 0.001). Venous thrombo-embolic events, arterial embolizations, and cerebrovascular accidents were documented in 28 of 411 patients (6.8%). Neonatal death rate was 3.1%. CONCLUSION: PPCM occurs in women from different ethnic backgrounds globally. Despite marked differences in socio-economic background, mode of presentation was largely similar. Embolic events and persistent heart failure were common within 1 month post-diagnosis and required intensive, multidisciplinary management.

Financial impact of ivabradine on reducing heart failure penalties under the Hospital Readmission Reduction Program.

OBJECTIVE: The introduction of the Hospital Readmission Reduction Program (HRRP) has led to renewed interest in developing strategies to reduce 30 day readmissions among patients with heart failure (HF). In this study, a model was developed to investigate whether the addition of ivabradine to a standard-of-care (SoC) treatment regimen for patients with HF would reduce HRRP penalties incurred by a hypothetical hospital with excess 30 day readmissions. RESEARCH DESIGN: A model using a Monte Carlo simulation framework was developed. Model inputs included national hospital characteristics, hospital-specific characteristics, and the ivabradine treatment effect as quantified by a post hoc analysis of the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT). RESULTS: The model computed an 83% reduction in HF readmission penalty payments in a hypothetical hospital with a readmission rate of 22.95% (excess readmission ratio = 1.056 over the national average readmission rate of 21.73%), translating into net savings of $44,016. A sensitivity analysis indicated that the readmission penalty is affected by the specific characteristics of the hospital, including the readmission rate, size of the ivabradine-eligible population, and ivabradine utilization. CONCLUSIONS: The results of this study indicate that the addition of ivabradine to an SoC treatment regimen for patients with HF may lead to a reduction in the penalties incurred by hospitals under the HRRP. This highlights the role ivabradine can play as part of a wider effort to optimize the care of patients with HF.

Budget Impact of Adding Ivabradine to Standard of Care in Patients with Chronic Systolic Heart Failure in the United States.

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80% of which is directly attributable to hospitalizations. The SHIFT clinical study demonstrated that ivabradine plus standard of care (SoC) reduced HF-related and all-cause hospitalizations compared with SoC alone. OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related = $37,507; non-HF CV = $28,951; and non-CV = $17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2%, increasing 2% per year. RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of $0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine's reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was $0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers. DISCLOSURES: This study was funded by Amgen. Patel is employed by Amgen; Kielhorn was employed by Amgen at the time of the study but is no longer affiliated with Amgen. Borer, Böhm, Ford, and Komajda have received scientific support, consultative fees, and/or speakers honoraria from Servier and Amgen in connection with SHIFT, the trial underlying this analysis. Borer also has received consultative fees from Celladon, Pfizer, ARMGO, Cardiorentis, Novartis, and Takeda USA. Kansal, Dorman, Krotneva, and Zheng are employees of Evidera, which was hired to assist with this study. Tavazzi has received research grants and consultation fees from Servier in connection with this study and has had advisory board memberships with Boston Scientific, Servier, Cardiorentis, Medtronic, St. Jude Medical, and CVie Therapeutics. Study concept and design were contributed by Dorman and Keilhorn, along with the other authors. Tavazzi, Komajda, Ford, BÖhm, and Borer oversaw collection of the data. Tavazzi, Komajda, Ford, BÖhm, and Borer (along with Karl Swedberg) formed the Executive Committee of SHIFT, the trial underlying this analysis. The manuscript was written by Kansal, along with the other authors, and revised by Borer and Patel, with assistance from the other authors.

[The root of the deep and fast ongoing evolution of both structure and methodology of clinical research]. / Le radici della rapida e profonda evoluzione in corso della struttura e della metodologia della ricerca clinica.

The growing scientific knowledge and technology development are leading to radical changes in biological and medical research. The prevalent lines of development deal with a pragmatic evolution of controlled clinical trials, a massive diffusion of observational research, which is progressively incorporated in clinical practice, new models and designs of clinical research, the systematic use of information technology to build up vast networks of medical centers producing huge amounts of shared data to be managed through the big data methodology, personalized as well as precision medicine, a reshaped physician-patient relationship based on a co-working principle. All this is leading to profound changes in public health governance, a renewal of clinical epidemiology and prevention, a modified structure of several specific sectors of medical care, hopefully guided by scientific evidences. A few aspects of such an evolving picture are discussed in this article.

Appropriateness of Prescriptions of Recommended Treatments in Organisation for Economic Co-operation and Development Health Systems: Findings Based on the Long-Term Registry of the European Society of Cardiology on Heart Failure.

OBJECTIVE: This observational study aimed to identify clinical variables and health system characteristics associated with incomplete guideline application in drug treatment of patients with chronic heart failure (HF) across 15 countries. METHODS: Three data sets were used: European Society of Cardiology Heart Failure Registry, Organisation for Economic Co-operation and Development's Health System Characteristics Survey, and Organisation for Economic Co-operation and Development Health Statistics 2013. Patient and country variables were examined by multilevel, multiple logistic regression. The study population consisted of ambulatory patients with chronic HF and reduced ejection fraction. Inappropriateness of prescription of pharmacological treatments was defined as patients not prescribed at least one of the two recommended treatments (angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers and beta-blockers) or treated with both medications but at suboptimal dosage and in absence of documented contraindication/intolerance. RESULTS: Of 4605 patients, 1097 (23.8%) received inappropriate drug prescriptions with a large variation within and across countries, with 18.5% of the total variability accounted for by between-country health structure characteristics. Patient-level characteristics such as having mitral regurgitation (odds ratio 1.4; 95% confidence interval 1.1-1.7) was significantly associated with inappropriate prescription of recommended drugs, whereas chronic obstructive pulmonary disease (odds ratio 0.7; 95% confidence interval 0.5-0.9) was associated with more appropriate prescriptions. Among the country-level variables, incentives or obligation to comply with guidelines increased the probability of prescription appropriateness. CONCLUSIONS: Combining clinical variables with health system characteristics is a promising exercise to explain the appropriateness of recommended drug prescriptions. Such an understanding can help decision makers to design more effective policies to improve adherence to guidelines, improve health care outcomes, and potentially reduce costs.

[Remarks on polyparametric assessment of sudden death risk for primary prevention ICD implantation in patients with left ventricular dysfunction of ischemic and non ischemic etiology. Italian Association of Hospital Cardiologists (ANMCO) Experts Position Paper]. / Considerazioni su una valutazione poliparametrica nella stratificazione del rischio di morte improvvisa per l'indicazione all'impianto di cardioverter-defibrillatore in prevenzione primaria, nella disfunzione ventricolare sinistra di origine ischemica e non ischemica. Position paper dell'Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO).

It is generally recognized that current guidelines, based on ejection fraction criteria, do not allow appropriate selection of patients for implantable cardioverter-defibrillator (ICD) therapy in the primary prevention of sudden death, thus hindering the optimal use of ICD in patients with left ventricular dysfunction of ischemic and nonischemic etiology. Ejection fraction alone has limitations in both sensitivity and specificity. Assessment of the risk for sudden death using a combination of multiple tests (ejection fraction associated with one or more different arrhythmic risk markers) could partially compensate for these limitations. In this position paper, the potential usefulness of a polyparametric assessment using some of the most investigated risk markers of sudden death is discussed, including late gadolinium enhancement cardiac magnetic resonance, programmed ventricular stimulation, T-wave alternans, autonomic tone, biomarkers, and genetic testing.

Italian Survey on Prevalence and Disease Management of Chronic Heart Failure and Chronic Obstructive Pulmonary Disease comorbidity in ambulatory patients. SUSPIRIUM study rationale and design.

BACKGROUND: Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality worldwide. Through shared risk factors and pathophysiological mechanisms, CHF and COPD frequently coexist. The concurrent disease has important therapeutic implications and independently predicts worsened mortality, impaired functional status, and health service use. However, assessment of the comorbidity varies widely according to the population studied, diagnostic criteria and measurement tools applied. Both syndromes have been studied extensively but largely separately, mostly in the domain of the pulmonologist for COPD and in the domain of the cardiologist for CHF. STUDY OBJECTIVES AND DESIGN: The aim of the study is to evaluate in an Italian outpatients setting (10 cardiology and 10 pulmonology centers from the same institution) the prevalence, clinical profile and the routine diagnostic, functional and therapeutic work-up applied by cardiologists and pulmonologists in the presence/suspicion of concurrent disease in patients in a stable phase of their disease. For this purpose, CHF and COPU outpatients will be enrolled in a multicenter, nationwide, prospective observational study. Risk estimation of comorbidity will be based on suspected, documented or patient-reported diagnosis of COPD/CHF. In the absence of documented concurrent diagnosis, each specialist will describe the diagnostic, functional and therapeutic work-up applied. CONCLUSION: The design of the study focused on the diagnostic validation of the CHF-COPD comorbidity aims to provide relevant new information on the assessment of the coexistent condition in the cardiac and pulmonary outpatients setting and on specialty-related different diagnostic and therapeutic strategies of comorbidity utilized in real life clinical practice. The symptomatic and prognostic benefits resulting from a combined approach to CHF/COPD could outweigh those attainable by treating either condition alone.

The importance of patient-reported outcomes: a call for their comprehensive integration in cardiovascular clinical trials.

Patient-reported outcomes (PROs), such as symptoms, health-related quality of life (HRQOL), or patient perceived health status, are reported directly by the patient and are powerful tools to inform patients, clinicians, and policy-makers about morbidity and 'patient suffering', especially in chronic diseases. Patient-reported outcomes provide information on the patient experience and can be the target of therapeutic intervention. Patient-reported outcomes can improve the quality of patient care by creating a holistic approach to clinical decision-making; however, PROs are not routinely used as key outcome measures in major cardiovascular clinical trials. Thus, limited information is available on the impact of cardiovascular therapeutics on PROs to guide patient-level clinical decision-making or policy-level decision-making. Cardiovascular clinical research should shift its focus to include PROs when evaluating the efficacy of therapeutic interventions, and PRO assessments should be scientifically rigorous. The European Society of Cardiology and other professional societies can take action to influence the uptake of PRO data in the research and clinical communities. This process of integrating PRO data into comprehensive efficacy evaluations will ultimately improve the quality of care for patients across the spectrum of cardiovascular disease.

New devices in heart failure: an European Heart Rhythm Association report: developed by the European Heart Rhythm Association; endorsed by the Heart Failure Association.

Several new devices for the treatment of heart failure (HF) patients have been introduced and are increasingly used in clinical practice or are under clinical evaluation in either observational and/or randomized clinical trials. These devices include cardiac contractility modulation, spinal cord stimulation, carotid sinus nerve stimulation, cervical vagal stimulation, intracardiac atrioventricular nodal vagal stimulation, and implantable hemodynamic monitoring devices. This task force believes that an overview on these technologies is important. Special focus is given to patients with HF New York Heart Association Classes III and IV and narrow QRS complex, who represent the largest group in HF compared with patients with wide QRS complex. An overview on potential device options in addition to optimal medical therapy will be helpful for all physicians treating HF patients.

Cost-effectiveness of highly purified omega-3 polyunsaturated fatty acid ethyl esters in the treatment of chronic heart failure: results of Markov modelling in a UK setting.

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 RESULTS: Results 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. CONCLUSIONS: By 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.

Adherence to guidelines is a predictor of outcome in chronic heart failure: the MAHLER survey.

AIMS: The impact on outcome of the implementation of European guidelines for the treatment of chronic heart failure (CHF) has not been evaluated. We investigated the consequences of adherence to care by cardiologists on the rate of CHF and cardiovascular (CV) hospitalizations and time to CV hospitalization. METHODS AND RESULTS: We constructed class adherence indicators for angiotensin-converting enzyme (ACE)-inhibitors, beta-blockers, spironolactone, diuretics, and cardiac glycosides and GAIs (GAI3 adherence to first three classes of heart failure medication, GAI5 adherence to five classes). In the study, 1410 evaluable patients (mean age 69, 69% males, New York Heart Association (NYHA) II: 64%, III: 34%, IV: 2%) were enrolled and followed up for 6 months by 150 randomly selected cardiologists/cardiology departments from six European countries (France, Germany, Italy, The Netherlands, Spain, and UK). Overall, adherence to treatment guidelines was 60 (GAI3) and 63% (GAI5) and was better for ACE-I (88%) or diuretics (82%) than for cardiac glycosides (52%), beta-blockers (58%), and spironolactone (36%). In the three tertiles of the population defined by a decreasing mean adherence score value, CHF and CV hospitalization rates were, respectively, 6.7, 9.7, and 14.7% and 11.2, 15.9, and 20.6% (P<0.002 and P<0.001, respectively). Global adherence indicator GAI3 was an independent predictor of time to CV hospitalization in a multi-variable model together with NYHA Class, history of CHF hospitalization, ischaemic aetiology, diabetes mellitus, and hypertension. CONCLUSION: We demonstrate that adherence of physicians to treatment guidelines is a strong predictor of fewer CV hospitalizations in actual practice. There is a need to develop further quality improvement programmes in this condition.

[Economic impact of cardiac resynchronization therapy in patients with heart failure. Available evidence and evaluation of the CRT-Eucomed model for analysis of cost-effectiveness]. / L'impatto economico della terapia di resincronizzazione in pazienti con scompenso cardiaco. Evidenze disponibili e valutazione del modello CRT-Eucomed per l'analisi del rapporto costo-efficacia.

Several clinical trials show that cardiac resynchronization therapy (CRT) in patients with moderate-severe heart failure increases survival, improves quality of life and reduces hospital admissions. The high cost of this new technology, incurred by health organizations at the moment of the implant, requires to assess whether its use is economically rational for the Italian Health Service. The paper summarizes evidences of the impact of CRT on the use of hospital resources and on quality of life, and presents a model to calculate incremental costs per quality adjusted life years (QALYs) gained in patients with moderate-severe heart failure treated with optimal medical therapy. The model is based on efficacy data drawn from clinical trials and on other information concerning the Italian context collected and validated by a team of experts from Assobiomedica and the Italian Federation of Cardiology. The model estimates that the incremental cost per QALY gained attributable to CRT is Euro 63,225 if all effects (years of life gained, increased quality of life and reduction of hospital costs) are censored at the end of the first year after the implant and Euro 21,720 if all effects are censored at the end of the third year. Cost-effectiveness of CRT is thus strongly dependent upon the duration of its effects: longer benefits of the therapy compensate initial costs and thus make the technology more cost-effective. In order to get better estimates of the economic profile of CRT it is required to collect more precise data from routine practice on survival, quality of life and hospital resources. The model presented can be easily adapted to take into account new evidence and to calculate cost per QALY gained in regional and local contexts.

Participation versus education: the GISSI story and beyond.

Approximately 20 years ago, the Italian cardiology community realized the scientific importance and the potential impact on clinical practice of the new concept of evidence-based medicine and launched (without funds) a national megatrial, the Gruppo Italiano por lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) study. In the following 20 years, 4 GISSI trials have been carried out, and a fifth is underway. The conceptual process that followed this experience shaped the role of the medico-scientific society that sponsored these trials as an active player in research, with the public health as the common target. This process of getting together was founded on the basic principle that active participation can be much more effective and rewarding than education (a passive process). Accordingly, further studies were undertaken dealing with clinical epidemiology, observational outcome research introduced complementarily to develop lines of clinical investigation along 2 mainstreams: ischemic heart disease and heart failure. The original decision to directly sponsor countrywide research projects in critical and relevant areas of care had broader implications not only for the role of scientific societies, but more generally for the nurture of independent research, which is today widely recognized to be at risk. The articulation among experimental, observational, and evaluative protocols in which all caring physicians are allowed to be producers and authors and not simply users of knowledge can favor a cultural continuity that minimizes the risk of parallelisms and gaps between research and care.