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Nationwide survey on acute heart failure in cardiology ward services in Italy

Luigi Tavazzi, Aldo P. Maggioni, Donata Lucci, Giuseppe Cacciatore, Gerardo Ansalone, Fabrizio Oliva, Maurizio Porcu
DOI: http://dx.doi.org/10.1093/eurheartj/ehi845 1207-1215 First published online: 7 April 2006


Aims Chronic heart failure (HF) is recognized as an important public health problem but little attention has been focused on acute-stage HF.

Methods and results Nationwide, prospective, observational study setting 206 cardiology centres with intensive cardiac care units. During 3 months, 2807 patients diagnosed as having de novo acute HF (44%) or worsening chronic HF (56%) were enrolled. Acute pulmonary oedema was the presenting clinical feature in 49.6% of patients, cardiogenic shock in 7.7%, and worsened NYHA functional class in 42.7% of cases. Anaemia (Hb<12 g/dL) was present in 46% of patients, renal dysfunction (creatinine ≥1.5 mg%) in 47%, and hyponatraemia (≤136 mEq/L) in 45%. An ejection fraction (EF)>40% was found in 34% of cases. Intravenous diuretics, nitrates, and inotropes were given to 95, 51, and 25% of patients, respectively. The median duration of hospital stay was 9 days. In-hospital mortality rate was 7.3%. Older age, use of inotropic drugs, elevated troponin, hyponatraemia, anaemia, and elevated blood urea nitrogen were independent predictors of all-cause death; prior revascularization procedures and elevated blood pressure were indicators of a better outcome. The rehospitalization rate within 6 months was 38.1%, all-cause mortality from discharge to 6 months was 12.8%.

Conclusion Acute HF is an ominous condition, needing more research activity and resources.

  • Heart failure
  • Acute heart failure
  • Survey
  • Observational research
  • Inotropes
  • Nitrates


Chronic heart failure (HF) has long been recognized as an important public health problem and intensive clinical research has been performed in this area during the last two decades. Conversely, with the exception of the cases of myocardial infarction, little attention has been focused on acute failure or exacerbation of chronic HF. This is surprising considering the epidemiology of this severe condition,1 which is the most frequent cause of hospitalization in subjects aged more than 65 years.2,3

Accordingly, in a tradition of co-operative nationwide clinical research in Italy and specific attention dedicated to HF through both observational and intervention studies,47 a mid-term observational study on acute HF was undertaken. The goals were:

  1. to describe the demographic, clinical, and biological characteristics of patients with acute HF admitted to cardiology departments endowed with an intensive cardiac care unit (ICCU);

  2. to describe the diagnostic and therapeutic approaches undertaken in hospital and the routine practice of cardiology centres in following the patients after discharge;

  3. to assess the in-hospital outcome of patients with either de novo acute HF or acute exacerbations of chronic HF, and the prognostic predictors of this outcome.

Methods and patients

This was a multicentre, prospective, observational, nationwide study. All 396 existing Italian departments with an ICCU were invited to participate in the study. Two hundred and six agreed to participate. These hospitals were good representatives of the geographical distribution and level of technology of the network of the Italian hospitals with an ICCU (Table 1). The enrolment period went from 1 March 2004 to 31 May 2004. Each centre was committed to enrol all consecutive patients with symptoms and signs of acute HF admitted to their cardiology wards during the abovementioned period. The diagnosis of acute HF was made according to the criteria recommended by the ESC Guidelines 2001,8 which were reported in the protocol of the study. In particular, the coexistence of both symptoms of acute de novo or worsening HF and objective evidence of cardiac dysfunction were required. The need for intravenous drug infusion was a further requirement for patient's enrolment. In the guidelines, the differential diagnosis between acute pulmonary oedema and cardiogenic shock was underlined; not so for the distinction between pulmonary congestion and alveolar oedema which was not specifically required. The only exclusion criterion was a patient's unwillingness to participate. Patients were asked to sign an informed consent to anonymous management of their individual data. Local Institutional Review Boards were informed of the study according to national rules. The study being strictly observational, follow-up visits after discharge were not specifically encouraged but left to the usual practice care of the participating centres. The assessment of the rate of patients who are routinely followed-up in clinical practice in Italy was, therefore, one of the aim of the study. The availability of the follow-up information is reported in Figure 1.

Figure 1

Patients outcome and data availability.

View this table:
Table 1

Representativeness of hospitals with an ICCU participating in the survey with respect to hospitals with an ICCU in Italy

Participating hospitals (n=204) (%)Italian hospitals with an ICCU (n=386) (%)
North89 (44)165 (43)
Center42 (20)90 (23)
South73 (36)131 (34)
With Cath Lab (non-interventional)25 (12)46 (12)
With interventional Cath Lab/cardiac surgery63 (31)115 (30)

Because of the observational nature of the study, without any treatment evaluation, a formal calculation of the study size was not applicable. On the basis of the previous studies4,5 and administrative data, the expectation was to collect information of nearly 3000 patients. Data were collected by the participating centres in a central database using a web connection.

Categorical variables are presented as percentages. The duration of in-hospital stay is presented as the median value and inter-quartile ranges (IQR). Other continuous variables are presented as their means with SD. Univariate associations between baseline characteristics, main diagnostic procedures, pharmacological/non-pharmacological treatments, and all-cause in-hospital mortality were tested. Categorical variables were compared by the χ2 test and continuous variables by the t-test or the Mann–Whitney U-test. Age, gender, presenting clinical profile, type of HF (de novo/worsening), and all the variables at entry significantly associated at the unadjusted analysis with all-cause mortality were included in a multivariable analysis (logistic model) with the aim of identifying the independent predictors of all-cause in-hospital mortality. The linearity of the continuous variables was tested using the restricted cubic spline. There were many data missing (6.5%) for the blood urea nitrogen (BUN) variable. A multiple imputation technique was therefore used to avoid the loss of the information in those subjects with some missing variables. According to this procedure, five complete datasets were obtained using the MICE package9 and five full data analyses were completed. Finally, the results were pooled using the method of Barnard and Rubin.10 A P-value <0.05 was considered statistically significant. All tests were two-sided. Analyses were performed with SAS system software (SAS Institute Inc., Cary, NC, USA) and R Development Core Team (R Foundation for Statistical Computing, Vienna).


During the 3 months of enrolment, 2807 patients were included in the database. Seventy percent of these were admitted to the cardiology wards directly from home, 24% from other wards of the same hospital (almost half of these from the emergency department), and 6% from other hospitals.

The patients' demographics, clinical history, and clinical data on admission to the cardiology wards are reported in Table 2. The mean age was 73±11 years and 46% of the patients were more than 75 years old. Comorbid conditions were frequent. Acute HF events requiring hospital admission were classified as new onset (de novo) HF in 44% of patients, and acute decompensation of chronic HF (acute-on-chronic HF) in 56%. An acute myocardial infarction was diagnosed in 20% of the cases. The HF profiles were classified by the investigators as acute pulmonary oedema in 49.6% of patients, cardiogenic shock in 7.7%, a worsened NYHA functional class (III and IV) in the remaining 42.7% of cases. The signs of congestion were reported as shown in Table 3. The large majority of patients had signs of peripheral and pulmonary congestion confirmed by chest X-ray in 90% of cases. Although the specification of the radiological evidence of alveolar oedema was not required, in patients classified as acute pulmonary oedema the radiological evidence of pulmonary congestion and pulmonary rales coexisted. Signs of mitral valve regurgitation were reported in 57% of the patients. Systolic blood pressure (SBP) was >140 mmHg in 43% of patients. Heart rate was greater than 100 bpm in 38% of patients in sinus rhythm and in 60% of the 798 patients with atrial fibrillation (AF). The QRS interval was greater than 120 ms in 29% of the cases. The most frequent aetiology of heart disease was ischaemia (46%). An ischaemic episode was considered the precipitating factor for acute destabilization of HF in 33% of cases overall (40% in patients with de novo HF).

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Table 2

Demographic, clinical history, and clinical data on admission

Total population (n=2807)Worsening HF (n=1572)De novo HF (n=1235)
Age (years, mean±SD) 73±11 72±11 73±12
Age >75 years (%) 45.7 44.0 47.9
Sex (female, %) 39.5 36.7 43.1
Clinical history
 Previous myocardial infarction (%) 36.5 43.8 27.2
 Previous revascularization (%) 19.1 24.1 12.8
 Paroxysmal AF (%) 21.3 24.0 17.8
 Implanted cardiac defibrillator (%)  4.5  7.3  1.0
 Pacemaker (%) 12.4 16.7  7.0
 Previous stroke (%)  9.2  9.4  8.9
 Chronic obstructive pulmonary disease (%) 29.7 33.8 24.5
 Peripheral vascular disease (%) 12.0 13.2 10.2
 Renal failure (%) 24.7 32.3 14.9
 Diabetes mellitus (%) 38.4 41.1 34.7
 History of hypertension (%) 65.6 66.2 64.9
 Active smoker (%) 14.5 11.7 18.0
 Ischaemic (%) 46.0 46.6 45.2
 Hypertensive (%) 14.9 11.3 19.5
 Valvular (%) 11.4 11.8 10.9
 Idiopathic (%) 14.1 18.6  8.4
 Other (%)  9.3  8.5  5.7
 Non-determinable/unknown (%)  4.3  3.2  5.7
SBP (mmHg)
 SBP (mean±SD)141±37138±36146±37
 <90 (%)  4.8  4.3  5.4
 90–140 (%) 52.1 57.4 45.2
 >140 (%) 43.1 38.2 49.4
Heart rate (bpm)
 Patients with sinus rhythmn=1729n=901n=828
 Heart rate (mean±SD) 97±22 96±21 98±22
 <60 (%)  3.1  2.7  3.6
 60–80 (%) 21.2 23.1 19.2
 81–100 (%) 37.7 38.5 36.7
 >100 (%) 38.0 35.7 40.5
Patients with AFn=798n=449n=349
 Heart rate (mean±SD)111±28106±27118±28
 <60 (%)  2.5  3.1  1.7
 60–80 (%) 13.4 16.9 8.9
 81–100 (%) 24.6 26.7 21.8
 >100 (%) 59.5 53.2 67.6
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Table 3

Clinical and cardiac signs and chest X-ray picture at admission

n (%)
Clinical findings (n=2807)
 Jugular venous pressure >6 cm1100 (39.2)
 Peripheral congestion1654 (58.9)
 Rales2452 (87.4)
 Third heart sound943 (33.6)
 Mitral regurgitation1609 (57.3)
 Wheeze889 (31.7)
 Aortic stenosis243 (8.7)
 Aortic regurgitation272 (9.7)
Chest X-ray (n=2477)
 Cardiothoracic ratio ≥0.51637 (66.1)
 Venous congestion2218 (89.5)
 Pleural effusion685 (27.7)

In 55% of cases left ventricular (LV) function had already been evaluated before the hospital admission and in 89% of these patients LV systolic function was depressed. An echocardiogram was recorded during the hospital stay in 92% of the patients. LV ejection fraction (LVEF) was <30%, between 30 and 40%, and >40% in 29%, 37%, and 34% of the patients, respectively.

The biohumoral data are reported in Table 4. Defining anaemia according to the WHO criteria, a haemoglobin (Hb) concentration <13 g/dL in men and <12 g/dL in women,11 56% of the patients were anaemic at the first assessment performed. Using more stringent criteria (Hb <12 g/dL in both sexes), 46% were anaemic and 16% were severely anaemic (Hb <10 g/dL). The level of plasma creatinine indicated moderate renal dysfunction (132.6–221.0 µmol/L) in 33% of the cases and severe dysfunction (>221.0 µmol/L) in 13% of the cases. Plasma sodium concentrations were below or equal to 136 mEq/L in 45% of the cases.

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Table 4

Biohumoral data on admission

Total population (n=2807)Worsening HF (n=1572)De novo HF (n=1235)
Haemoglobin (g/dL)Available for 2758 patientsAvailable for 1538 patientsAvailable for 1220 patients
 Haemoglobin (mean±SD)12.1±2.1 11.9±2.0 12.3±2.1
 <10.0 (%)16.2 18.3 13.4
 10.0–12.0 (%)32.8 34.0 31.4
 12.1–15.0 (%)43.9 41.6 47.0
 >15.0 (%)7.1 6.1 8.4
Creatinine (μmol/L)Available for 2768 patientsAvailable for 1544 patientsAvailable for 1224 patients
 Creatinine (mean±SD)150.3±88.4 1.8±1.0 1.6±1.1
 <132.6 (%)53.5 46.9 61.9
 132.6–221.0 (%)33.2 36.9 28.4
 >221.0 (%)13.3 16.2 9.7
eGFR (mL/min/1.73 m2)Available for 2727 patientsAvailable for 1524 patientsAvailable for 1203 patients
 <3012.4 15.6 8.3
 30–6046.7 52.3 39.7
 >6040.9 32.1 52.0
Sodium (mEq/L)Available for 2755 patientsAvailable for 1537 patientsAvailable for 1218 patients
 Sodium (mean±SD)137±5136±5137±4
 <132 (%)12.4 16.0 7.8
 132–136 (%)32.5 32.8 32.3
 >136 (%)55.1 51.2 59.9
Potassium (mEq/L)Available for 2757 patientsAvailable for 1538 patientsAvailable for 1219 patients
 Potassium (mean±SD)4.6±0.7 4.6±0.7 4.6±0.6
 <3.6 (%)2.8 3.0 2.5
 3.6–5.5 (%)89.5 88.9 90.2
 >5.5 (%)7.7 8.1 7.3
BUN (mg/dL)Available for 2624 patientsAvailable for 1457 patientsAvailable for 1167 patients
 BUN (mean±SD) 81±53 86±54 74±51
 <50 (%)28.7 24.5 33.9
 50–100 (%)47.8 48.2 47.2
 >100 (%)23.5 27.3 18.9
  • eGFR, estimated glomerular filtration rate.

Pharmacological and other therapeutic intervention rates are reported in Table 5. Besides diuretics, which were used in 95% of the cases, intravenous therapy consisted of nitrates (mostly nitroglycerin) in 51% of the patients and inotropes in 25%. The inotropes were almost exclusively adrenergic agents (dobutamine, dopamine) and were used more frequently in patients with low blood pressure. Oral drug therapies prescribed in patients with worsening HF before hospitalization and at discharge are reported in Table 6.

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Table 5

Pharmacological treatment and other interventions

IV treatments (%)Total population (n=2807)Worsening HF (n=1572)De novo HF (n=1235)
 Other diuretics8.810.86.2
 Aortic counterpulsation1.20.81.7
  • PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting.

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Table 6

Pharmacological treatments in patients with worsening HF

Pharmacological treatment (%)All patients (n=1572)Patients discharged alive (n=1460)
Before hospitalizationBefore hospitalizationAt discharge
Aldosterone blockers34.434.566.3
Calcium channel blockers13.814.113.0
Oral anticoagulants28.929.332.9
  • ACE-I, angiotensin converting enzyme-inhibitors; ARBs, angiotensin receptor blockers.

The median time spent in hospital was 9 days (IQR: 6–13); 69% of patients (65% and 74% of those with acute-on-chronic and de novo HF, respectively) were admitted to the ICCU for a median time of 4 days (IQR: 2–6). The all-cause in-hospital death rate was 7.3% (and was defined as cardiac in 90% of cases): 7.5% in patients with de novo HF and 7.1% in those with worsening HF. Patients with cardiogenic shock had the highest mortality rate (25.4%).

The results of the multivariable analysis to identify the independent predictors of in-hospital all cause mortality are reported in Table 7. Use of inotropic drugs, older age, elevated troponin, hyponatraemia, anaemia, and elevated BUN were the independent predictors of death. Prior coronary revascularization and elevated blood pressure resulted as indicators of better outcome.

View this table:
Table 7

Independent predictors of in-hospital all-cause mortality

VariablesPOR95% CI
Intravenous inotropes<0.00012.8621.909–4.292
Elevated troponin0.00711.8821.188–2.984
Prior revascularization0.04840.5880.347–0.996
SBP at admission (continuous)<0.00010.9850.979–0.992
Age (continuous)0.00041.0361.016–1.056
BUN (continuous)0.00121.0071.003–1.012
Haemoglobin (continuous)0.01020.8930.819–0.974
Sodium (continuous)0.02690.9620.930–0.996

According to the study design, the patients were followed-up after discharge as usually planned by the centre: 1406 patients (54% of those discharged alive) underwent a clinical follow-up, whereas 1196 (46%) did not. In 1771 patients (68% of the hospital survivors) the vital status from discharge to 6 months was known (Figure 1). The baseline characteristics and the type of index admission in patients for whom vital status was known and unknown were similar. All-cause mortality from discharge to 6 months was 12.8%, higher in patients with acute-on-chronic HF (16.0%) than in the group with de novo HF (8.4%). The readmission rate within 6 months was 38.1%, higher in patients with acute-on-chronic HF (41.0%) than in the group with de novo HF (34.1%). The reason for readmission was defined as cardiovascular in 83% of the cases and as HF in 54%.


With the increased prevalence of HF, there is a concomitant increase in the number of related hospitalizations and as HF progresses the risk of acute exacerbation increases. In Italy, there were nearly 185 000 hospital admissions for HF in 2001, this being the most frequent cause of hospitalization in subjects over 65 years old.2,3,12 Clinical destabilizations leading to hospitalization are associated with haemodynamic and neurohormonal alterations which can contribute to progressive ventricular dysfunction and dilation, mitral regurgitation, increased wall stress, and progressive myocyte loss as a result of apoptosis and necrosis.1316 Considering the epidemiology, pathophysiology, and outcome, acute HF requires prompt and intensive care. However, the therapeutic approach to this risky condition did not change much in the last few decades.

In the network of hospitals participating in this survey, which was a good representative of the national health system, a roughly similar occurrence of de novo and worsened chronic HF was observed among the patients admitted to the cardiology wards with a diagnosis of acute HF. Twenty percent of cases were associated with an acute myocardial infarction. Nearly 50% of patients had acute pulmonary oedema as the first manifestation of cardiac pump failure. This finding is at variance to the rates of this clinical pattern in other surveys, being much higher than the 8% rate reported in the IMPACT-HF registry17 and 13% observed in a recent two-centre survey.18 There are probably several reasons for this discrepancy: the definition of acute pulmonary oedema1719 including the accuracy in differentiating pulmonary congestion with or without evidence of alveolar oedema, which types of patients are directed to the cardiology ward, and the different process of care provided before the patient is admitted.

The biohumoral profile was markedly altered in patients with acute HF. Either anaemia or hyponatraemia were present in about half of the patients. This presumably reflects a state of circulatory overload with haemodilution, neurohormonal hyperactivation, and regional flow redistribution with a reduced renal supply, as indicated by the high rate of elevated creatinine blood level. At least one-third of patients with acute HF of non-ischaemic aetiology had increased blood levels of troponin, indicating myocardial jeopardy. This is probably an underestimation because troponin determination was not done or sequentially planned in all centres. Similar findings have been reported by others.1516,18,20

Among the patients with chronic HF in whom the left LVEF was known before the index admission, systolic ventricular function was reported as depressed in about 90%. The LVEF was evaluated in hospital in 92% of patients and appeared to be reduced in two-thirds. These data were recorded during hospital stay, not necessarily on admission, and centralized quality control was not done. However, we did not confirm a high prevalence of HF with preserved LV systolic function either before or during the hospitalization in our acute HF patients. In both the ADHERE Registry21 and the EuroHeart Survey,22 about half of the patients in whom the LVEF was determined showed a value ≥40%, whereas in both IMPACT-HF17 and Rudiger et al.18 prospective studies and a Canadian retrospective study,23 a preserved (≥50%) LVEF was found in one-fourth of patients.

As found in other studies,13,1719,21,22 the most extensively used class of drugs was diuretics. Furosemide was administered intravenously to almost all patients with acute HF, in more than half of them at a dose greater than 80 mg/die. Although congestion must be relieved urgently in order to improve symptoms and clinically stabilize the patients, it is known that large doses of diuretics may impair renal function.24 Thus, some caution should be exercised when using these drugs at high dose, and research into therapeutic alternatives is warranted. Overall, one-fourth of the patients were given beta-receptor agonists such as dobutamine or dopamine, a drug little investigated in HF.19 This therapeutic approach was adopted, in spite of a few reports of unfavourable effects attributed to these stimulating cardiovascular drugs,19,25,26 mainly in patients with low blood pressure, in whom cardiac output is assumed to be decreased the effects of cardiovascular unloading are uncertain and the need to sustain the blood pressure at a level compatible with an acceptable regional blood flow is compulsory. Levosimendan, which has shown a promising performance in clinical trials27,28 had not been yet incorporated into clinical practice in Italy at the time this survey was performed. Nitroglycerin is used in many patients with acute HF, mostly in those with presumed ongoing myocardial ischaemia and/or elevated blood pressure. In spite of being a class I recommendation in the European Guidelines,19 this is a practice-based rather than evidence-based approach. Other drugs and therapeutic procedures are seldom used. Overall, it should be acknowledged that the therapeutic portfolio available for patients with acute HF is very limited.

The in-hospital all-cause mortality rate in our survey (7.3%) was higher than in the ADHERE21 and OPTIMIZE29 Registries (4%) as well as in a retrospective survey performed in the Worcester area (5%),30 whereas it was similar to that in the EuroHeart Survey (6.9%)22 and lower than that in the study by Rudiger et al. (11%).18 A reason for the difference in mortality rates may lie in the time spent in hospital: on average 4 days in the US surveys and registries21,29,30 and 9–11 days in the European surveys.18,22 Considering the high mortality rate of patients with acute HF during the first days following the index event, doubling the time spent in hospital may almost double the deaths recorded in hospital. Indeed, the 3-month cumulative mortality rate is similar in both European18,22 and American21,29 studies (13–13.5%). This consideration does not apply to the IMPACT–HF in which the in-hospital mortality was surprisingly low (2.6%) in spite of 8 days of hospital stay.17 In contrast, the French EFICA study, which enrolled 599 elderly HF patients (82% with acute pulmonary oedema and 27% with cardiogenic shock) had an in-hospital mortality rate of 29%.31 Here the difference in outcome is related to the different characteristics of the enrolled population. Despite the adjustments for all possible confounding factors, the need of inotropes was the strongest predictor of in-hospital all-cause mortality, probably because these drugs are used in patients considered to be at the highest risk of death. Release of myocardial troponin, older age, elevated BUN, hyponatraemia, and anaemia were the most important markers of a poor in-hospital outcome. A strong inverse correlation was noted between SBP and outcome: the higher the pressure, the lower the in-hospital mortality (Figure 2). Explanations for this relation may be that hypertension can act as the major cause of decompensation and can be controlled by treatment. Conversely, a low SBP implies particularly severe ventricular pump failure. Finally, a history of revascularization procedures appeared to be predictive of a favourable outcome.

Figure 2

All-cause in-hospital mortality according to SBP at admission.

While complete in-hospital information was available for all patients, according to the observational nature of the study, follow-up visits were not specifically planned after discharge. The physicians were required to apply the routine practice of their centre. In nearly 50% of the population, a clinical follow-up was planned. Vital status at 6 months was known for about two-thirds of the patients. Both mortality and rehospitalization rates were high, but we cannot exclude that the rates of these events were even higher in those patients for whom information were not available.

Strengths and limitations

The main characteristics of this survey are that the participating centres are representative of the Italian network of cardiology centres and that it adheres to the observational spirit of research. The data reported therefore represent the real epidemiological and clinical picture of acute HF in a large European country, as well as the therapeutic decisions concerning this condition and the continuity of care after discharge from hospital.

The limitations are related to the strengths. The patients were enrolled in cardiology centres and the population, therefore, does not include patients who died in emergency wards or casualty departments of hospitals, or those admitted to wards other than cardiology ones. Hence, this survey does not depict the epidemiology of acute HF, but rather the epidemiology of acute HF as managed by cardiologists. Patients admitted in a cardiology ward were nearly 40% of the total population of patients admitted for acute HF in the Italian hospitals participating in a previous survey conducted in our country.4 Furthermore, the follow-up information represent the spontaneous process of care of patients with acute HF and these follow-up data are, therefore, only partial. However, imposing clinical controls or additional contacts by protocol would have deformed the natural evolution of events.


Overall, the high mortality rate of patients with acute HF is a clear demonstration of our impotence in the face of this condition. The burden of mortality of acute HF is similar to that of acute myocardial infarction during its acute stage, but it is much higher afterwards. This further emphasizes the striking difference in the amount of clinical research dedicated to the two conditions, acute HF has been almost ignored by both clinical researchers and industry until the very last few years. Only one drug labelled for acute HF—neseritide—has been approved in the last 15 years in the USA and, similarly, only one drug—levosimendan—has been approved for the same indication in the last 15 years in Europe. The lack of new drugs potentially useful for this indication and, consequently, the lack of resources dedicated by industry, has condemned this clinical area to a marginal role. It is time to dedicate resources and research to this orphan field.


L.T. and A.P.M. contributed to the conception and design of the study, analysis and interpretation of data, drafting of the manuscript, and procurement of funding. D.L. contributed to the acquisition, analysis and interpretation of data, critical revision of the manuscript, and the statistical analyses. G.C., G.A., F.O., and M.P. contributed to the conception and design of the study, and critical revision of the manuscript. The sponsor of the study was the Heart Care Foundation (Fondazione Italiana per la Lotta alle Malattie Cardiovascolari), a non-profit independent institution which is also the owner of the database. Database management and quality control of the data were the responsibility of the research centre of the Italian Association of Hospital Cardiologists (ANMCO). The study was partially supported by an unrestricted educational grant from Abbott, Italy. No fees were provided to either cardiology centres or investigators. No representatives of Abbott were included in any of the study committees. The Steering Committee of the study had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of interest: We declare that we have no conflict of interest.


Steering Committee: Luigi Tavazzi (Chairman), Giuseppe Cacciatore (Co-Chairman), Gerardo Ansalone, Fabrizio Oliva, Maurizio Porcu. Executive Committee: Aldo P. Maggioni (Chairman), Luigi Tavazzi, Giuseppe Cacciatore. Scientific-Logistic Secretariat: Gianna Fabbri, Lucio Gonzini, Donata Lucci, Giampietro Orsini, Laura Sarti. Participating Centres and Investigators (by geographic region): Piemonte Acqui Terme (P.L. Roncarolo, M.T. Zunico); Biella (M. Marcolongo, N. Andrighetti); Borgomanero (M. Zanetta, A. Paino); Cuneo (E. Uslenghi, F. Meinardi); Moncalieri (M.T. Spinnler, A. De Bernardi); Mondovì (C. Bruna, P.C. Martinetti); Novara (A.S. Bongo, M. Rizzotti); Pinerolo (E. Bellone, D. Sappè); Rivoli (M.R. Conte, L. Mainardi); Savigliano (B. Doronzo, L. Correndo); Torino A.O. S. Giovanni Battista (G. Trevi, S. Bergerone); Torino Ospedale Mauriziano (E. Richiardi, A. Bonzano); Torino Ospedale Maria Vittoria (R. Trinchero, A. Chinaglia); Torino Ospedale Giovanni Bosco (R. Bevilacqua, B. Bianchini); Verbania (E.M. Bianchi, S. Randazzo); Aosta (M. De Marchi, C. Gianonatti); Lombardia Bergamo Ospedali Riuniti (A. Gavazzi, U. Veritti); Bergamo Cliniche Gavazzeni (P. Sganzerla, M. Bonin); Brescia Ospedale Sant'Orsola FBF (C. Rusconi); Brescia Casa di Cura Poliambulanza (S. Riva, G. Musmeci); Casalmaggiore (C. Bonifazi, S. Arisi); Cernusco Sul Naviglio (E.M. Greco, S. Dell'Orto); Cinisello Balsamo (G. Bozzi, G. Tommasini); Codogno (A. Sgalambro, D. Covini); Como (G. Ferrari, A. Politi); Cremona (S. Pirelli, M. Carini); Erba (W. Bonini, D. Agnelli); Esine (E. Ferrara, P. Bonetti); Garbagnate Milanese (G. Rovelli, G. Lureti); Lodi (M. Orlandi, R. Osti); Manerbio (E. Renaldini, A. Masa); Mantova (R. Zanini, M.R. Ferrari); Merate (F. Achilli, G. Lecchi); Milano Ospedale Niguarda (S. Klugmann, M. Frigerio); Milano Ospedale FBF (B. Brusoni, M. Negrini); Milano Ospedale L. Sacco (M. Viecca, R. Sala); Milano Casa di Cura Santa Rita (V. Celano, M. Bianchi); Milano Ospedale San Luca-Centro Auxologico (G. Leonetti, G. Perego); Paderno Dugnano (S. Biasi, D. Massa); Pavia Ospedale Policlinico San Matteo IRCCS (P.J. Schwartz, G.M. De Ferrari); Pieve di Coriano (M.C. Brunazzi, M. Pasqualini); Ponte San Pietro (F. Doni, S. Todd); Seriate (P. Giani, T. Nicoli); Sondrio (S. Giustiniani, A. Zecca); Tradate (M. Onofri, L. Amati); Varese (J.A. Salerno Uriarte); Vigevano (M. Romanò, G. Graziano); Vizzolo Predabissi (M. Lombardo, P. Quorso); Voghera (G. Marinoni, F. Chiofalo); P.A. Bolzano (W. Pitscheider, W. Rauhe); Merano (W. Oberlechner, K. Dritan); Veneto Belluno (G. Catania, O. Palatini); Camposampiero (A. Zampiero, A. Di Marco); Castelfranco Veneto (L. Celegon, A. Desideri); Conegliano Veneto (P. Delise, C. Marcon); Este (F. Corbara, M. Formichi); Feltre (M. Guarnerio, F. De Cian); Mirano (P. Pascotto, P. Sarto); Montebelluna (G. Neri, A. Daniotti); Rovigo (P. Zonzin, M. Carraro); Thiene (B. Martini, S. Cannas); Treviso (P. Stritoni, S. Giacomelli); Verona (P. Zardini, M. Cicoira); Udine Gorizia (D. Igidbashian, R. Chiozza); Pordenone (G.L. Nicolosi, R. Piazza); Trieste (G. Sinagra, M. Millo); Udine (P. Fioretti, D. Miani); Liguria Genova-Sestri Ponente (S. Domenicucci, S. Costa); Imperia (G. Musso, A. Ranise); Pietra Ligure (F. Chiarella, A.M. Nicolino); Sanremo (F. Miccoli, G. Benza); Sarzana-Loc. S. Caterina (G. Filorizzo, R. Petacchi); Emilia Romagna Bentivoglio (G. Di Pasquale, R. Vandelli); Bologna Ospedale Maggiore C.A. Pizzardi (D. Bracchetti, P.C. Pavesi); Bologna Ospedale Policlinico S.Orsola-M.Malpighi (M. Sanguinetti, C. Lolli); Bologna Ospedale Bellaria (G. Pinelli, S. Urbinati); Carpi (S. Ricci, V. Neri); Castelnuovo Ne' Monti (U. Guiducci, G. Toni); Fidenza (P. Moruzzi, E. Buia); Forlì (F. Rusticali, D. Ferrini); Guastalla (G. Bruno, A. Mazzi); Imola (C. Antenucci, S. Negroni); Lugo (S. Della Casa, M. Gobbi); Montecchio Emilia (A. Navazio, E. Catellani); Piacenza (A. Capucci, M. Piepoli); Ravenna (A. Maresta, G. Bellanti); Riccione (L. Rusconi, P. Del Corso); Rimini (G. Piovaccari, F. Bologna); Sassuolo (F. Melandri, V. Agnoletto); Toscana Castelnuovo Garfagnana (D. Bernardi, M. Cabib); Cecina (F. Chiesa, E. Venturini); Empoli (V. Mazzoni, A. Dell'Elce); Firenze Ospedale S.M. Nuova (F. Marchi, M. Milli); Firenze AO. Careggi Servizio di Cardiologia (G.F. Gensini, S. Valente); Firenze A.O. Careggi Area Funzionale Cardiologia (G. Masotti, L. Boncinelli); Lido di Camaiore (A. Pesola, L. Robiglio); Montepulciano (G. Giappichini, A. Bianchi); Pescia (W. Vergoni, G. Italiani); Piombino (G. Micheli, S. Isidori); Pisa (S.M. De Tommasi, A.M. Paci); Poggibonsi (P. Baldini, M. Romei); Pontedera (G. Tartarini, S. Viani); Prato (R.P. Dabizzi, F. Pestelli); Siena (R. Favilli, M. Pastore); Umbria Città di Castello (M. Cocchieri, D. Severini); Gubbio (S. Mandorla, M. Buccolieri); Perugia (G. Ambrosio, G. Alunni); Terni (G. Rasetti, C. Milici); Marche Ancona (G. Perna, S. Moretti); Ascoli Piceno (L. Moretti, G. Gregori); Camerino (R. Amici, G. Patteri); Lazio Albano Laziale (G. Ruggeri, S. Petronzelli); Civitavecchia (M. Di Gennaro); Colleferro (S. Toscano, M. Mennuni); Formia (P. Tancredi, M. Costigliola); Latina (P.G. Gelfo, R. Di Rosa); Pomezia (D. Ricci, F. Vennittilli); Roma Ospedale San Camillo I U.O. Cardiologia (E. Giovannini, G. Pulignano); Roma Ospedale San Camillo II Divisione di Cardiologia con UTIC (S.F. Vajola, E. Biffani); Roma Ospedale San Giovanni (A. Boccanelli, N. Pagnoni); Roma Ospedale Santo Spirito (V. Ceci, N. Aspromonte); Roma Ospedale San Giacomo In Augusta (G. Altamura, F.C. Rossi); Roma Ospedale San Pietro FBF (F. Ferri, C. Vitucci); Roma Ospedale Madre Giuseppina Vannini (G. Ansalone); Roma Aurelia Hospital (F. Proietti, F. Gasbarri); Abruzzo Chieti (G. D'Orazio, A. Taccardi); Giulianova (P. Di Sabatino, T. Strangi); L'Aquila (G. Castellani, D. Bultrini); Lanciano (L. Leonzio, C. Tucci); Penne (A. Vacri, F. Romanazzi); Popoli (C. Frattaroli, J. Jafaritorkmani); Sulmona (L. Fagagnini); Vasto (G. De Simone, G. Levantesi); Termoli (D. Staniscia, E. Beato); Campania Acerra (P. Guarini); Ariano Irpino (G. Bellizzi, C. Lo Conte); Avellino (G. Rosato, M.R. Pagliuca); Aversa (G. De Marco, P. Iodice); Battipaglia (M. Maina, L. Tedesco); Benevento (B. Villari, Q. Ciampi); Caserta (G. Corsini, M. Catanzaro); Castellammare di Stabia (L. Caliendo, L. De Vivo); Cava dei Tirreni (L. Pagano, A. Spadera); Mercato San Severino (V. Capuano, G. Di Maso); Mercogliano (M. Agrusta, G. De Fazio); Napoli Ospedale Ascalesi (A. Imperatore, G. Ferlito); Napoli Policlinico Univ. Federico II (B. Trimarco, L. Argenziano); Napoli Clinica Mediterranea (B. Ricciardelli, B. Golia); Nocera Inferiore (U. De Martino, G. Bove); Piedimonte Matese (R. Battista, E. Proia); Pollena Trocchia (F. Napolitano); Pozzuoli (G. Sibilio, L. Cavuto); Salerno (F. Silvestri, C. Baldi); San Giuseppe Vesuviano (M. Ammirati, S. Dangelo); Sarno (V. Messina, C. D'Ambrosi); Scafati (S. Baldi, V. Iuliano); Torre Annunziata (F. Di Palma, N. Vitiello); Puglia Bari Ospedale Consorziale Policlinico (I. De Luca, E. Fino); Bari Ospedale San Paolo (G. Brindicci, A. De Giosa); Bari-Carbonara Ospedale di Venere (C. D'Agostino, G. Scalera); Barletta (M. Russo, Patruno); Casarano (G. Pettinati, F. De Santis); Cerignola (M. Cannone, R. Torraco); Copertino (G. De Rinaldis, A. Calcagnile); Gallipoli (F. Cavalieri, C. Minelli); Putignano (E. Cristallo, M.G. Campagna); Scorrano (E. De Lorenzi, O. De Donno); Taranto Ospedale SS. Annunziata (N. Baldi, A. Iervoglini); Taranto Casa Di Cura Villa Verde (V. Polini, S. Vitanza); Terlizzi (F. Bux, P. Caldarola); Potenza (F. Sisto, V. Viggiano); Venosa (S. Barbuzzi); Calabria Cetraro (G. Sollazzo, M. Matta); Cosenza Ospedale SS. Annunziata (N. Venneri, G. Misuraca); Cosenza INRCA Istituto Cardiovasculop. Senili (E. Feraco, A. Nicoletti); Lamezia Terme (A. Butera, V. Pileggi); Polistena (R.M. Polimeni, A. Amato); Reggio Calabria (G. Pulitanò, A. Ruggeri); Rossano (S. Salituri, A. Gallerano); Sicilia Augusta (G. Chiarandà, M.L. Cavarra); Caltagirone (D. Malfitano, C. Cinnirella); Castelvetrano (F. Pompeo, N. Cascio Ingurgio); Catania Ospedale Garibaldi (S. Mangiameli, G. Arcidiacono); Catania Ospedale Vittorio Emanuele II (A. Circo, R. Romano); Catania Ospedale Ferrarotto (G. Giuffrida, G. Licciardello); Cefalù (F. Clemenza); Erice (G.B. Braschi, G. Ledda); Gela (R. Di Caro, C. Sillitti); Mazara del Vallo (N. Di Giovanni, A. Pepe); Messina (R. Grassi, G. Di Tano); Milazzo (L. Vasquez, G. Pizzimenti); Palermo A.R.N.A.S. Ospedale Civico e Benfratelli (E. D'Antonio, M.G. Fiorino); Palermo Ospedale V. Cervello (A. Canonico, G. Celona); Palermo Casa di Cura Villa Maria Eleonora (M. Traina, A. Guarneri); Patti (I. Lo Cascio, A. Lo Cascio); Pedara (S. Tolaro, M. Barillà); Ragusa (V. Spadola, M.L. Guarrella); Siracusa (E. Mossuti, G. Romano); Taormina (R. Evola, A.E. Lo Schiavo); Sardegna Cagliari Ospedale San Giovanni di Dio (L. Meloni); Cagliari Presidio Ospedaliero SS. Trinità (C. Lai, G. Pili); Cagliari A.O. G. Brotzu-S. Michele (M. Porcu, G. Scorcu); Carbonia (R. Aste, S. Cherchi); Nuoro (G. Mureddu, F. Delrio); Oristano (S.M. Marchi, M.V. Demontis); Sassari (P. Terrosu, F. Uras).


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