Clinical research
European Heart Journal (2006) 27, 1207–1215
doi:10.1093/eurheartj/ehi845
Heart failure
Nationwide survey on acute heart failure in cardiology
ward services in Italy
Luigi Tavazzi1*, Aldo P. Maggioni2, Donata Lucci2, Giuseppe Cacciatore3, Gerardo Ansalone4,
Fabrizio Oliva5, and Maurizio Porcu6 on behalf of the Italian survey on Acute Heart
Failure Investigators
1
Department of Cardiology, IRCCS Policlinico S. Matteo, Piazzale Golgi, 2-27100 Pavia, Italy; 2 ANMCO Research Center,
Florence, Italy; 3 Department of Cardiology, Ospedale S. Giovanni Addolorata, Rome, Italy; 4 Department of Cardiology,
Ospedale Madre Giuseppina Vannini, Rome, Italy; 5 Department of Cardiology, Ospedale Niguarda, Milan, Italy; and
6
Department of Cardiology, Ospedale S. Michele Brotzu, Cagliari, Italy
Received 28 March 2005; revised 23 February 2006; accepted 9 March 2006; online publish-ahead-of-print 7 April 2006
Heart failure;
Acute heart failure;
Survey;
Observational research;
Inotropes;
Nitrates
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.
Introduction
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,4–7 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);
* Corresponding author. Tel: +39 0 55 5001703; fax: +39 0 55 583400.
E-mail address: [email protected]
(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
& The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: [email protected]
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KEYWORDS
1208
L. Tavazzi et al.
Table 1 Representativeness of hospitals with an ICCU participating in the survey with respect to hospitals with an ICCU in Italy
North
Center
South
With Cath Lab
(non-interventional)
With interventional
Cath Lab/cardiac surgery
Participating
hospitals
(n ¼ 204) (%)
Italian hospitals
with an ICCU
(n ¼ 386) (%)
89 (44)
42 (20)
73 (36)
25 (12)
165 (43)
90 (23)
131 (34)
46 (12)
63 (31)
115 (30)
Figure 1
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).
Results
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
Patients outcome and data availability.
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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.
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 interquartile ranges (IQR). Other continuous variables are presented as
their means with SD. Univariate associations between baseline
characteristics, main diagnostic procedures, pharmacological/nonpharmacological treatments, and all-cause in-hospital mortality
were tested. Categorical variables were compared by the x 2 test
Nationwide survey on acute HF
1209
Table 2 Demographic, clinical history, and clinical data on admission
Total population
(n ¼ 2807)
De novo HF
(n ¼ 1235)
73 + 11
45.7
39.5
72 + 11
44.0
36.7
73 + 12
47.9
43.1
36.5
19.1
21.3
4.5
12.4
9.2
29.7
12.0
24.7
38.4
65.6
14.5
43.8
24.1
24.0
7.3
16.7
9.4
33.8
13.2
32.3
41.1
66.2
11.7
27.2
12.8
17.8
1.0
7.0
8.9
24.5
10.2
14.9
34.7
64.9
18.0
46.0
14.9
11.4
14.1
9.3
4.3
46.6
11.3
11.8
18.6
8.5
3.2
45.2
19.5
10.9
8.4
5.7
5.7
141 + 37
4.8
52.1
43.1
138 + 36
4.3
57.4
38.2
146 + 37
5.4
45.2
49.4
n ¼ 1729
97 + 22
3.1
21.2
37.7
38.0
n ¼ 798
111 + 28
2.5
13.4
24.6
59.5
n ¼ 901
96 + 21
2.7
23.1
38.5
35.7
n ¼ 449
106 + 27
3.1
16.9
26.7
53.2
n ¼ 828
98 + 22
3.6
19.2
36.7
40.5
n ¼ 349
118 + 28
1.7
8.9
21.8
67.6
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).
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
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Age (years, mean + SD)
Age .75 years (%)
Sex (female, %)
Clinical history
Previous myocardial infarction (%)
Previous revascularization (%)
Paroxysmal AF (%)
Implanted cardiac defibrillator (%)
Pacemaker (%)
Previous stroke (%)
Chronic obstructive pulmonary disease (%)
Peripheral vascular disease (%)
Renal failure (%)
Diabetes mellitus (%)
History of hypertension (%)
Active smoker (%)
Aetiology
Ischaemic (%)
Hypertensive (%)
Valvular (%)
Idiopathic (%)
Other (%)
Non-determinable/unknown (%)
SBP (mmHg)
SBP (mean + SD)
,90 (%)
90–140 (%)
.140 (%)
Heart rate (bpm)
Patients with sinus rhythm
Heart rate (mean + SD)
,60 (%)
60–80 (%)
81–100 (%)
.100 (%)
Patients with AF
Heart rate (mean + SD)
,60 (%)
60–80 (%)
81–100 (%)
.100 (%)
Worsening HF
(n ¼ 1572)
Table 3 Clinical and cardiac signs and chest X-ray picture at
admission
n (%)
Clinical findings (n ¼ 2807)
Jugular venous pressure .6 cm
Peripheral congestion
Rales
Third heart sound
Mitral regurgitation
Wheeze
Aortic stenosis
Aortic regurgitation
Chest X-ray (n ¼ 2477)
Cardiothoracic ratio 0.5
Venous congestion
Pleural effusion
1100
1654
2452
943
1609
889
243
272
(39.2)
(58.9)
(87.4)
(33.6)
(57.3)
(31.7)
(8.7)
(9.7)
1637 (66.1)
2218 (89.5)
685 (27.7)
1210
L. Tavazzi et al.
Table 4 Biohumoral data on admission
Worsening HF (n ¼ 1572)
De novo HF (n ¼ 1235)
Available for 2758
12.1 + 2.1
16.2
32.8
43.9
7.1
Available for 2768
150.3 + 88.4
53.5
33.2
13.3
Available for 2727
12.4
46.7
40.9
Available for 2755
137 + 5
12.4
32.5
55.1
Available for 2757
4.6 + 0.7
2.8
89.5
7.7
Available for 2624
81 + 53
28.7
47.8
23.5
Available for 1538 patients
11.9 + 2.0
18.3
34.0
41.6
6.1
Available for 1544 patients
1.8 + 1.0
46.9
36.9
16.2
Available for 1524 patients
15.6
52.3
32.1
Available for 1537 patients
136 + 5
16.0
32.8
51.2
Available for 1538 patients
4.6 + 0.7
3.0
88.9
8.1
Available for 1457 patients
86 + 54
24.5
48.2
27.3
Available for 1220 patients
12.3 + 2.1
13.4
31.4
47.0
8.4
Available for 1224 patients
1.6 + 1.1
61.9
28.4
9.7
Available for 1203 patients
8.3
39.7
52.0
Available for 1218 patients
137 + 4
7.8
32.3
59.9
Available for 1219 patients
4.6 + 0.6
2.5
90.2
7.3
Available for 1167 patients
74 + 51
33.9
47.2
18.9
patients
patients
patients
patients
patients
patients
eGFR, estimated glomerular filtration rate.
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 mmol/L) in 33% of the cases and severe dysfunction (.221.0 mmol/L) in 13% of the cases. Plasma
sodium concentrations were below or equal to 136 mEq/L
in 45% of the cases.
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.
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
Table 5 Pharmacological treatment and other interventions
IV treatments (%)
Total
population
(n ¼ 2807)
Worsening
HF
(n ¼ 1572)
De novo
HF
(n ¼ 1235)
Diuretics
Furosemide
Other diuretics
Nitrates
Nitroglycerin
Nitroprusside
Inotropes
Dopamine
Dobutamine
Others
95.3
95.0
8.8
51.3
49.5
2.7
24.6
18.5
12.9
2.9
95.9
95.4
10.8
47.3
45.0
3.2
28.8
21.1
15.7
3.4
94.5
94.3
6.2
56.4
55.2
2.2
19.1
15.1
9.4
2.2
5.5
1.3
1.2
3.9
1.5
0.8
7.4
1.1
1.7
Interventions
PCI/CABG
Ultrafiltration
Aortic counterpulsation
PCI, percutaneous coronary intervention; CABG, coronary artery bypass
grafting.
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%).
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Haemoglobin (g/dL)
Haemoglobin (mean + SD)
,10.0 (%)
10.0–12.0 (%)
12.1–15.0 (%)
.15.0 (%)
Creatinine (mmol/L)
Creatinine (mean + SD)
,132.6 (%)
132.6–221.0 (%)
.221.0 (%)
eGFR (mL/min/1.73 m2)
,30
30–60
.60
Sodium (mEq/L)
Sodium (mean + SD)
,132 (%)
132–136 (%)
.136 (%)
Potassium (mEq/L)
Potassium (mean + SD)
,3.6 (%)
3.6–5.5 (%)
.5.5 (%)
BUN (mg/dL)
BUN (mean + SD)
,50 (%)
50–100 (%)
.100 (%)
Total population (n ¼ 2807)
Nationwide survey on acute HF
1211
Table 6 Pharmacological treatments in patients with
worsening HF
Pharmacological
treatment
(%)
All patients
(n ¼ 1572)
Patients discharged
alive (n ¼ 1460)
Before
Before
At discharge
hospitalization hospitalization
62.5
11.7
72.5
34.4
63.0
11.9
73.1
34.5
73.3
13.7
84.2
66.3
80.9
32.0
19.5
33.6
13.8
80.9
32.6
18.9
33.0
14.1
94.2
45.1
24.9
39.4
13.0
24.2
28.9
24.7
29.3
30.8
32.9
43.2
43.4
51.5
ACE-I, angiotensin converting enzyme-inhibitors; ARBs, angiotensin
receptor blockers.
Table 7 Independent predictors of in-hospital all-cause
mortality
Variables
P
OR
95% CI
Intravenous inotropes
Elevated troponin
Prior revascularization
SBP at admission (continuous)
Age (continuous)
BUN (continuous)
Haemoglobin (continuous)
Sodium (continuous)
,0.0001
0.0071
0.0484
,0.0001
0.0004
0.0012
0.0102
0.0269
2.862
1.882
0.588
0.985
1.036
1.007
0.893
0.962
1.909–4.292
1.188–2.984
0.347–0.996
0.979–0.992
1.016–1.056
1.003–1.012
0.819–0.974
0.930–0.996
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.
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
Discussion
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.13–16
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 oedema17–19 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.15–16,18,20
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
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ACE-I
ARBs
ACE-I/ARBs
Aldosterone
blockers
Diuretics
Beta-blockers
Amiodarone
Nitrates
Calcium channel
blockers
Statins
Oral
anticoagulants
Antiplatelets
was defined as cardiovascular in 83% of the cases and as
HF in 54%.
1212
Figure 2
All-cause in-hospital mortality according to SBP at admission.
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.
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.
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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,13,17–19,21,22 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
L. Tavazzi et al.
Nationwide survey on acute HF
Conclusion
Acknowledgements
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.
Appendix
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); Mondovı̀ (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); Forlı̀ (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,
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on February 12, 2016
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.
1213
1214
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
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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);
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