Download Multicenter Prospective Observational Study on Acute and Chronic

Original Article
Multicenter Prospective Observational Study on Acute and
Chronic Heart Failure
One-Year Follow-up Results of IN-HF (Italian Network on Heart Failure)
Outcome Registry
Luigi Tavazzi, MD; Michele Senni, MD; Marco Metra, MD; Marco Gorini, MS;
Giuseppe Cacciatore, MD; Alessandra Chinaglia, MD; Andrea Di Lenarda, MD;
Andrea Mortara, MD; Fabrizio Oliva, MD; Aldo P. Maggioni, MD; on the behalf of IN-HF
(Italian Network on Heart Failure) Outcome Investigators*
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Background—Clinical observational studies on heart failure (HF) deal mostly with hospitalized patients, few with chronic
outpatients, all with no or limited longitudinal observation.
Methods and Results—This is a multicenter, nationwide, prospective observational trial on a population of 5610 patients,
1855 hospitalized for acute HF (AHF) and 3755 outpatients with chronic HF (CHF), followed up for 1 year. The cumulative
total mortality rate at 1 year was 24% in AHF (19.2% in 797 patients with de novo HF and 27.7% in 1058 with worsening
HF) and 5.9% in CHF. Cardiovascular deaths accounted for 73.1% and 65.3% and HF deaths for 42.4% and 40.5% of
total deaths in AHF and CHF patients, respectively. One-year hospitalization rates were 30.7% in AHF and 22.7% in
CHF patients. Among the independent predictors of 1-year all-cause death, age, low systolic blood pressure, anemia, and
renal dysfunction were identified in both acute and chronic patients. A few additional variables were significant only in
AHF (signs of cerebral hypoperfusion, low serum sodium, chronic obstructive pulmonary disease, and acute pulmonary
edema), whereas others were observed only in CHF patients (lower body mass index, higher heart rate, New York Heart
Association class, large QRS, and severe mitral regurgitation).
Conclusions—In this contemporary data set, patients with CHF had a relatively low mortality rate compared with those with
AHF. Rates of adverse outcomes in patients admitted for AHF remain very high either in-hospital or after discharge. Most
deaths were cardiovascular in origin and ≈40% of deaths were directly related to HF. (Circ Heart Fail. 2013;6:473-481.)
Key Words: epidemiology
■
D
heart failure
■
prognosis
studies had a transversal design with no or limited longitudinal observation, and no previous registry included cohorts
of patients with AHF and chronic HF (CHF) enrolled in the
same setting.
In Italy, through the series of the large cooperative GISSI
(Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto
Miocardico) randomized trials and nationwide observational
studies, a vast experience on pragmatic clinical research
has been achieved by cardiology centers, and an expert trial
coordinating center has been developed. In consideration of
the numerous limitations of available surveys and registries
on HF mentioned above and the availability of an expert
national clinical research structure, a nationwide registry
was performed with the following main characteristics and
uring the last decades, the interest in observational
research by medical societies, health authorities, and
drug or device companies has been rising for several reasons,
including monitoring the incorporation of new diagnostic–
therapeutic processes, and guidelines’ recommendations, need
of awareness of met and unmet clinical needs, and use of the
observational data as platform for continuous medical education and health authorities’ policy and strategy.
Clinical Perspective on p 481
Several studies have been conducted in patients with heart
failure (HF), particularly in those with acute HF (AHF), with
rather inconsistent results.1–14 For instance, the in-hospital
mortality rate ranged from <3%1 to >20%.5 Moreover, most
Received July 16, 2012; accepted February 25, 2013.
From the GVM Hospitals of Care and Research, Ettore Sansavini Health Science Foundation, Cotignola, Italy (L.T.); USC Cardiovascular Medicine,
Papa Giovanni XXIII Hospital, Bergamo, Italy (M.S.); Department of Cardiology, University and Spedali Civili, Brescia, Italy (M.M.); ANMCO Research
Center, Florence, Italy (M.G., A.P.M.); Department of Cardiology, San Giovanni—Addolorata Hospital, Rome, Italy (G.C.); Cardiology Department,
Maria Vittoria Hospital, Torino, Italy (A.C.); Cardiovascular Center, Azienda Servizi Sanitari n. 1 Triestina, Trieste, Italy (A.D.L.); Department of Clinical
Cardiology and Heart Failure, Policlinico di Monza, Monza, Italy (A.M.); and Cardiologia 2-Heart Failure and Heart Transplant Program, “A. De Gasperis”
Cardiovascular Department, Niguarda Hospital, Milan, Italy (F.O.).
*A list of participating centers and investigators is given in the Appendix.
Correspondence to Aldo P. Maggioni, MD, IN-HF Outcome Coordinating Center, ANMCO Research Center, Via La Marmora, 34 50121 Florence, Italy.
E-mail [email protected]
© 2013 American Heart Association, Inc.
Circ Heart Fail is available at http://circheartfailure.ahajournals.org
473
DOI: 10.1161/CIRCHEARTFAILURE.112.000161
474 Circ Heart Fail May 2013
goals: (1) representativeness of the current HF population
by implementing a network of enrolling centers of different
complexity balanced with respect to the Italian hospital
national network; (2) inclusion of both AHF and CHF
patients in sizable samples, enrolled in the same centers;
(3) systematic 1-year follow-up with a local monitoring to
limit the number of lost to follow-up; and (4) investigation
of clinical profiles, contemporary treatment, outcome rates,
and their predictors in both AHF and CHF cohorts. Baseline
characteristics and in-hospital findings of patients with AHF
have been reported elsewhere.15 In the present study we have
shown, and compared, the baseline characteristics and the
1-year outcomes of the AHF and CHF patients.
Methods
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This is a prospective, observational, nationwide study that involved
61 cardiology centers. The geographical distribution of hospitals
across the country and the overall profile of the participating cardiology institutions were representative of the national setting of cardiovascular care in Italy. Enrollment could occur during a routine
ambulatory visit (CHF patients) or at the time of admission to a cardiology ward (AHF patients). Patients’ enrollment lasted 2 years with a
minimal follow-up of 1 year. Outpatient visits were performed at 3, 6,
and 12 months after enrollment. Consecutiveness of enrollment was
recommended but not checked with an admission log. There were no
specific exclusion criteria, with the exception of age <18 years and
patient unwillingness to participate. AHF patients were enrolled only
if treated with intravenous therapy (diuretics, vasodilators, or inotropes). HF was classified as de novo HF in the absence of a history of
HF and worsening HF if a previous diagnosis or hospitalization for
HF was documented and a recent symptoms’ worsening was reported
by the patient and confirmed by the physician. If not documented, a
prior hospitalization was accepted as patient-reported. The patients
were also classified according to the clinical categories suggested by
the European Society of Cardiology guidelines.14
Patients were asked to sign an informed consent. Local Institutional
Review Boards were informed of the study according to Italian national rules. Being the study observational, no specific protocols or
recommendations for HF management were imposed. Current guidelines of HF,14 including the diagnostic criteria, were diffused and discussed during investigator meetings performed at the beginning of the
study before starting patients’ enrollment. Participating doctors were
invited to be adherent to them. Data were collected using a web-based
system and stored in a central database.
Statistical Analysis
Categorical variables are presented as percentages, whereas continuous variables are presented as mean and SD if normally distributed, or
as median and interquartile range, if not. Categorical variables were
compared by the χ2 test and continuous variables by the t test or the
Mann–Whitney U test. Plots of the Kaplan–Meier curves for time to
all-cause death, time to admission to hospital for HF, and time to allcause death or HF hospitalization were performed. All the variables
at entry which were statistically significant at univariate analysis and
variables predefined as of relevant clinical interest were included in
the multivariable model (Cox model) to identify the independent
predictors of all-cause death from study entry to 1-year follow-up,
separately for AHF and CHF. Age, systolic blood pressure (BP), heart
rate, and body mass index were considered as continuous variables,
whereas laboratory measures, not being available for all patients,
were considered as categorical, using clinical cutoffs and defining a
dummy variable for missing values. We considered as start point for
the survival analyses the date of enrollment in the study. A P value of
<0.05 was considered statistically significant. All tests were 2-sided.
Analyses were performed with SAS system software, version 9.2.
Figure 1. Patient disposition. AHF indicates acute heart failure;
CHF, chronic heart failure; and pts, patients.
Results
From November 2007 to December 2009, 5610 patients were
enrolled, 3755 were ambulatory patients with CHF and 1855
were patients admitted for AHF (797 with de novo HF and
1058 with worsening HF). One-year survival and hospitalizations’ data were available for 97.3% and 97.8% of patients
with CHF and for 96.2% and 93.8% of patients with AHF,
respectively (Figure 1). Seventy-nine percent of CHF patients
and 78% of AHF patients had a 12-month follow-up clinical
visit. In these patients data on therapy were recorded. Data on
patients who died during the whole study period were not considered in these analyses. The clinical status at 12 months was
ascertained by a telephone interview for patients not attending
a clinical visit.
Chronic Versus Acute (De Novo and Worsening)
HF: Clinical Profiles at Enrollment
Table 1 reports the characteristics of the study population.
Patients with HF associated with an acute myocardial infarction were 239 (12.9%). AHF patients were older and more
likely women than those with CHF. Mean values of systolic
BP and heart rate as well as of body mass index were significantly higher in patients with AHF. The left ventricular
ejection fraction was measured in 3804 patients, the mean
value was identical in the 2 groups (38%) with a similar rate
of patients with ejection fraction ≥40% (40.3% in CHF and
41.6% in AHF patients; P=0.44). Patients with AHF had a
higher rate of comorbidities than CHF patients. Notably, these
differences between acute and chronic patients were amplified when the subgroups with de novo and worsening HF
were considered separately. The latter group showed a higher
prevalence of comorbidities with more severe abnormalities
of some biomarkers (hyponatremia, anemia, higher levels
of blood urea nitrogen, and creatinine), whereas the former
showed higher values of glycemia, heart rate, and systolic BP
(Table 1).
One-Year Outcomes
Mortality and hospitalization rates in AHF and CHF during
the follow-up are reported in Table 2 and Figure 2.
Tavazzi et al Outcomes of Acute and Chronic Heart Failure 475
Table 1. Baseline Characteristics
Chronic HF (n=3755)
Age, y (mean±SD)
Age ≥70 y, %
Acute HF (n=1855)
P Value*
WHF (n=1058)
DN-HF (n=797)
P Value†
69±12
72±12
<0.0001
72±11
72±13
0.14
56
64
<0.0001
66
63
0.16
Women, %
24
40
<0.0001
37
43
0.01
Ischemic pathogenesis, %
46
42
0.02
45
38
0.003
27±4
28±5
<0.0001
28±6
28±5
0.32
22
29
<0.0001
29
29
0.78
126±19
134±33
<0.0001
129±30
141±34
<0.0001
14
20
<0.0001
24
15
<0.0001
70 [60–78]
90 [73–110]
<0.0001
82 [70–100]
95 [80–116]
<0.0001
38±11
38±14
0.87
37±14
39±14
0.007
Treated hypertension, %
43
58
<0.0001
56
61
0.03
Diabetes mellitus, %
30
40
<0.0001
43
37
0.008
BMI, kg/m2 (mean±SD)
BMI ≥30 kg/m2, %
SBP, mm Hg (mean±SD)
SBP <110 mm Hg, %
Heart rate, beats per minute (median [IQR])
LVEF, % (mean±SD)
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COPD, %
21
30
<0.0001
33
27
0.003
Renal dysfunction, %
21
32
<0.0001
39
24
<0.0001
History of atrial fibrillation, %
30
38
<0.0001
43
30
<0.0001
5
5
0.91
5
5
0.89
Peripheral artery disease, %
13
20
<0.0001
22
18
0.01
ICD, %
19
9
<0.0001
15
2
<0.0001
Previous stroke, %
CRT-D, %
7
4
<0.0001
6
1
<0.0001
CRT, %
2
2
0.60
2
1
0.005
Time from HF diagnosis >48 mo, %
54
52‡
0.31
52
NA
…
Hospital admission for HF in the previous year, %
57
46‡
<0.0001
46
NA
…
Pulmonary congestion, %
NA
78
…
76
81
0.004
Peripheral congestion, %
NA
56
…
61
49
<0.0001
Pulmonary or peripheral congestion, %
NA
88
…
88
89
0.40
Peripheral hypoperfusion, %
NA
12
…
12
11
0.53
Cold, %
NA
11
…
11
10
0.66
Somnolent, or confused, or sedated, %
NA
12
…
10
14
0.003
13.3±1.7
12.5±2.1
<0.0001
12.3±2.0
12.9±2.1
<0.0001
20
39
<0.0001
44
32
<0.0001
Hemoglobin, g/dL (mean±SD)
Hemoglobin <12 g/dL, %
1.2 [1.0–1.5]
1.2 [1.0–1.6]
0.11
1.3 [1.0–1.7]
1.1 [0.9–1.4]
<0.0001
Creatinine >1.5 mg/dL, %
Creatinine, mg/dL (median [IQR])
22
29
<0.0001
34
22
<0.0001
eGFR <60 mL/min per 1.73 m2, %
48
55
<0.0001
61
46
<0.0001
eGFR <30 mL/min per 1.73 m2, %
6
13
<0.0001
15
10
0.001
Glycemia >126 mg/dL, %
27
57
<0.0001
53
61
0.001
Sodium <136 mEq/L, %
9
19
<0.0001
23
13
<0.0001
<0.0001
BUN >50 mg/dL, %
NT-proBNP, pg/mL (median [IQR])
53
58
0.03
65
48
1041 [475–2027]
5168 [2518–11583]
<0.0001
4496 [2461–9492]
5964 [2680–13359]
0.14
BNP, pg/mL (median [IQR])
372 [149–803]
1112 [542–2225]
<0.0001
1200 [568–2314]
925 [540–2070]
0.37
hs-CRP, mg/L (median [IQR])
2.6 [0.7–5.0]
7.0 [2.2–19.0]
<0.0001
6.0 [1.5–14.9]
9.0 [3.3–23.1]
0.007
AHF indicates acute heart failure; BMI, body mass index; BNP, brain natriuretic peptide (available for 284 AHF patients and 59 CHF patients); BUN, blood urea
nitrogen (available for 1411 AHF patients and 1341 CHF patients); CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; creatinine available for
1823 AHF patients and 2303 CHF patients; CRT, cardiac resynchronization therapy; CRT-D, cardiac resynchronization therapy defibrillator; DN-HF, de-novo heart failure;
eGFR, estimaned glomerular filtration rate (available for 1823 AHF patients and 2303 CHF patients); glycemia available for 1733 AHF patients and 1452 CHF patients;
hemoglobin available for 1828 AHF patients and 2235 CHF patients; HF, heart failure; hs-CRP, C reactive protein (available for 389 AHF patients and 81 CHF patients);
ICD, implantable cardioverter defibrillator; IQR, interquartile range; LVEF, left ventricular ejection fraction (available for 1669 AHF patients and 2135 CHF patients);
NA, not available; NT-proBNP, N-terminal proBNP (available for 274 AHF patients and 174 CHF patients); SBP, systolic blood pressure; sodium available for 1763 AHF
patients and 1982 CHF patients; and WHF, worsening heart failure.
*Comparison between CHF and AHF.
†Comparison between WHF and DN-HF.
‡Evaluated on WHF patients.
476 Circ Heart Fail May 2013
Table 2. One-Year Outcomes
Death
All-cause death, %
Chronic HF (n=3755)
Acute HF (n=1855)
P Value*
<0.0001
5.9
24.0
Cause of death
n=222
n=446
Unknown, %
18.5
11.0
Non-CV death, %
16.2
15.9
CV death, %
65.3
73.1
Heart failure, %
40.5
42.4
Myocardial infarction, %
3.6
Arrhythmias, %
9.9
Other CV causes, %
0.02
DN-HF (n=797)
WHF (n=1058)
P Value†
<0.0001
19.2
27.7
n=153
n=293
6.5
13.3
18.3
14.7
75.2
72.0
37.3
45.1
10.5
15.0
8.2
6.7
7.8
6.1
0.02
0.08
0.09
11.3
13.5
15.0
12.6
Chronic HF (n=3755)
Acute HF (n=1737‡)
DN-HF (n=742‡)
WHF (n=995‡)
Patients admitted, %
22.7
30.7
<0.0001
22.1
37.1
<0.0001
Patients admitted for a CV reason, %
17.2
23.8
<0.0001
16.3
29.5
<0.0001
8.8
15.8
<0.0001
8.2
21.4
<0.0001
Hospitalization
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Patients admitted for HF, %
CV indicates cardiovascular; DN-HF, de novo heart failure; HF, heart failure; and WHF, worsening heart failure.
*Comparison between chronic HF and acute HF.
†Comparison between WHF and DN-HF.
‡Patients discharged alive.
Patients With AHF
Although all-cause mortality during hospital admission
was similar in patients with de novo and worsening HF
(6.9% vs 6.0%; P=0.41), the total mortality rate at 1 year
was 24.0% overall, being, respectively, 19.2% and 27.7%
(P<0.0001) in the 2 groups with AHF (Table 2; Figure 2A).
Notably, among patients with de novo and worsening HF
the postdischarge mortality rate constantly increased by 1%
and 2% per month, respectively, up to 1 year. Cardiovascular
deaths accounted for 73.1% of total deaths (whose 58%
HF-related), noncardiovascular deaths for 15.9%, whereas
an unknown cause was reported in 11.0% of AHF cases
(Table 2).
Among patients with AHF, the highest cumulative mortality
rate was observed in patients with cardiogenic shock (38.1%
at 1 year; mostly in-hospital, 23.8%), whereas the lowest mortality was observed in patients with an elevated systolic BP
at the time of admission to hospital (15.8% at 1 year; mostly
after discharge, 12.6%). Patients with AHF and concomitant
acute coronary syndrome showed a high mortality rate, both
in-hospital (13%) and after discharge (19.2%; Figure 3).
All-cause rehospitalizations occurred in 30.7% of patients
with AHF during the 1-year follow-up: for cardiovascular
causes in 23.8% of patients (two third of them for HF), for
noncardiovascular causes in 8.3%. Patients with worsening
HF showed a higher readmission rate for HF (21.4%) than
those with de novo HF (8.2%; Table 2; Figure 2B).
The great majority of patients with AHF presented signs
of peripheral or pulmonary congestion at the time of admission, whereas the rate of patients still showing some signs of
congestion at discharge was 8.2%. During the follow-up, this
turned out to be an ominous sign. The 1-year all-cause mortality of patients still congested at discharge was 37.1% versus
17.4% of those without congestion at discharge (P<0.0001).
All-cause rehospitalization rate seemed to be less affected by
this sign, being 37% versus 30%, respectively (P=0.08).
Pharmacological treatments reported at discharge and at
1-year follow-up are presented in Figure 4A. Overall, the neurohormonal modulators’ prescriptions at discharge from hospital were maintained or improved afterward.
The independent predictors of all-cause death at 1 year are
reported in Table 3. Older age, high serum creatinine, high
blood urea nitrogen, low serum sodium, chronic obstructive
pulmonary disease, acute pulmonary edema, anemia, and
symptoms of cerebral hypoperfusion were independently
associated with a higher annual mortality rate. Higher systolic BP was an independent protective factor. Both heart
rate, much higher in patients with worsening HF than in CHF
patients (P<0.0001), and left ventricular ejection fraction did
not emerge as independent predictors of events in the multivariable analysis. Biomarkers, such as brain natriuretic peptide and troponin, were measured at entry in a small number
of patients and they could not be, therefore, included in the
multivariable analyses.
Ambulatory Patients With CHF
The 1-year all-cause mortality of CHF patients was 5.9%
(Figure 2A; Table 2), much higher in patients in New York
Heart Association classes III and IV than in those in classes
I and II (14.5% vs 4.1%; P<0.0001). Death rate was higher,
but not significantly, in patients with an ischemic pathogenesis
than in those with a nonischemic pathogenesis (6.5% vs 5.4%;
P=0.17). Among the 222 patients with CHF who died at 1
year, 65.3% of deaths were because of cardiovascular reasons,
and, among them, HF was the most frequent cause (62.1%)
followed by arrhythmic deaths (15.2%). The 1-year admission
rate was 22.7%, only one-third (8.8%) were because of HF.
The proportion of HF hospitalizations was higher in patients
with severe HF, whereas in patients with ischemic pathogenesis the prevalent cause of hospitalization was cardiovascular
but not because of worsening HF.
The rate of the use of pharmacological treatments was high at
entry visit and did not change during the follow-up (Figure 4B).
Tavazzi et al Outcomes of Acute and Chronic Heart Failure 477
Figure 3. Acute heart failure (HF) cohort. All-cause mortality by
clinical profile at admission. ACS indicates acute coronary syndrome; CS, cardiogenic shock; PE, pulmonary edema; and RV,
right ventricular.
Discussion
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We have compared the clinical characteristics and outcomes
of 2 cohorts of patients, 1 of chronic stable HF outpatients
and 1 of hospitalized HF patients with de novo or worsening
HF. All patients of the 2 cohorts were enrolled in the same
hospitals by the same investigators. Both cohorts have been
followed up for 1 year being the survival status known at the
end of follow-up in 97.3% and 96.2% of chronic and acute
patients, respectively.
AHF Patients
Figure 2. Kaplan–Meier curves for all-cause death (A), admission
to hospital for HF (B), and all-cause death or admission to hospital for HF (C). HF indicates heart failure.
The variables independently associated with all-cause death
at 1 year are shown in Table 4. Older age, higher heart rate,
New York Heart Association class, anemia, larger QRS, high
creatinine level, and the presence of severe mitral regurgitation
were independently associated with a worse outcome, whereas
higher systolic BP and higher body mass index resulted as
independently associated with a lower mortality rate. As
expected, the use of β-blockers was associated with a lower
mortality, whereas the use of digitalis was with a higher one.
This study confirms our previous findings11 of a significant
difference between patients with de novo and worsening HF.
Most comorbidities, including diabetes mellitus, chronic
obstructive pulmonary disease, renal dysfunction, peripheral
artery disease, atrial fibrillation, and anemia were much more
frequent in the worsening HF group. Only renal dysfunction,
chronic obstructive pulmonary disease, and anemia emerged
as independent predictors of 1-year death at the multivariable
analysis, but presumably the global burden of comorbidities
influenced the event rates. For some of them, such as diabetes
mellitus, 1-year follow-up may have been too short to assess
their prognostic impact. Patients with de novo HF showed a
high event rate during the first weeks after admission. Afterward, their clinical course was more stable with the all-cause
death and HF hospitalization Kaplan–Meier curves showing
an approximately parallel course as compared with that of
CHF patients (Figure 2C) and the curve of HF hospitalization
rate overlapping that of CHF (Figure 2B).
Differently from patients with de novo HF, those hospitalized for worsening HF had much higher hospitalization and
mortality rates during the year after discharge. This pattern
is more impressive considering that both duration of HF (>48
months in 54% of patients with stable CHF and 52% of those
with worsening AHF; P=0.31) and HF hospitalization rate
in the previous year (57% and 46%, respectively; P<0.0001)
were similar in both groups, showing the crucial role of abrupt
worsening of symptoms in the natural history of HF.16
Among the variables analyzed as prognostic determinants
at admission, those related to acute decompensation, such as
water overload and neuro-hormonal activation (hyponatriemia and anemia), renal and circulatory dysfunction (high
creatinine and blood urea nitrogen, cerebral hypoperfusion,
478 Circ Heart Fail May 2013
Figure 4. Pharmacological treatments at
hospital discharge and 1 year of patients
with acute heart failure (A), and at study
entry and at the end of follow-up of
patients with chronic heart failure (B). The
analyses were performed only on patients
with information on prescriptions available at baseline and at 1-year follow-up.
ACE-I indicates angiotensin-converting
enzyme-inhibitor; AldoB, aldosterone
blockers; ARB, angiotensin II receptor
blocker; and βB, beta blockers.
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and acute pulmonary congestion),16 remained the most significant over the long term. Ejection fraction, available at hospital
entry, did not result as a significant predictor of 1-year mortality even at univariate analysis. Persistence of congestion at the
time of discharge affected a minority of patients (8%), probably because of the long duration of the hospitalization in Italy
(median 10 days).15 However, it was strongly related to the
1-year outcome, with a 2-fold increase in the mortality rate. It
is noteworthy that in these patients most late events were represented by death rather than by rehospitalization. These data
are in agreement with recent analyses showing the predictive
Table 3. Acute Heart Failure
value of worsening signs of HF during the initial hospitalization in patients with AHF.17–19
Other observational studies investigated the outcome predictors in patients with AHF.6 However, most of them included
observation periods limited to the hospital phase1,3,4,9,10,20 or
ranging from 1 to 6 months after discharge.5–8,10 Most studies, including follow-up lasting 1-year or longer, were single center studies2,12 or multicenter studies focusing on very
severe HF patients enrolled in general intensive care units.5
Table 4. Chronic Heart Failure
Hazard
Ratio
95% Confidence
Interval
P Value
NYHA III–IV vs I–II
2.52
1.86–3.41
<0.0001
Hemoglobin <12 vs ≥12, g/dL
2.79
1.89–4.12
<0.0001
Age (per 5-year increase)
1.18
1.09–1.28
<0.0001
Hazard Ratio
95% Confidence
Interval
P Value
Age (per 5-year increase)
1.20
1.14–1.27
<0.0001
HR (per 5-beats per minute increase)
1.09
1.04–1.15
0.0007
SBP (per 10-mm Hg increase)
0.90
0.86–0.93
<0.0001
Severe mitral regurgitation
2.03
1.31–3.15
0.002
Somnolent, confused, and
sedated
2.03
1.58–2.62
<0.0001
β-Blockers
0.64
0.47–0.86
0.004
Sodium <136 vs ≥136, mEq/L
1.68
1.35–2.09
<0.0001
SBP (per 10-mm Hg increase)
0.90
0.83–0.98
0.012
Creatinine >1.5 vs ≤1.5, mg/dL
1.67
1.31–2.12
<0.0001
BMI (per 1-kg/m2 increase)
0.96
0.92–0.99
0.015
BUN >50 vs ≤50, mg/dL
1.84
1.37–2.46
<0.0001
QRS ≥120 vs <120, ms
1.47
1.08–2.02
0.015
Hemoglobin <12 vs ≥12, g/dL
1.49
1.21–1.83
0.0002
Digitalis
1.43
1.05–1.93
0.022
APE vs NYHA III–IV
1.32
1.05–1.66
0.017
Creatinine >1.5 vs ≤1.5, mg/dL
1.57
1.06–2.34
COPD
1.25
1.02–1.53
0.034
Independent predictors of all-cause 1-year mortality (ordered by χ2 value).
The following variables were inserted in the Cox model: age, sex, SBP,
heart rate, pathogenesis, COPD, history of renal dysfunction, previous stroke/
TIA, peripheral artery disease, clinical presentation, worsening or de novo,
prior pace-maker, history of atrial fibrillation or atrial fibrillation at ECG,
peripheral congestion, cognitive status, ejection fraction in the previous 6
mo, QRS duration, creatinine, sodium, hemoglobin, and BUN. APE indicates
acute pulmonary edema; BUN, blood urea nitrogen; COPD, chronic obstructive
pulmonary disease; HF, heart failure; NHYA, New York Heart Association; SBP,
systolic blood pressure; and TIA, transient ischemic attack.
0.026
Independent predictors of all-cause 1-year mortality (ordered by χ value)
The following variables were inserted in the Cox model (backward selection):
age, sex, BMI, SBP, heart rate, duration of HF, HF hospitalization in the
previous year, pathogenesis, diabetes mellitus, history of AF or AF at ECG,
previous stroke/TIA, peripheral artery disease, chronic obstructive pulmonary
disease, prior pace-maker, NYHA class, rales, sound 3, peripheral congestion,
hemoglobin, creatinine, blood urea nitrogen, sodium, QRS, ejection fraction,
severe mitral regurgitation, angiotensin-converting enzyme-inhibitor or
angiotensin II receptor blocker, β-blockers, digitalis, aldosterone blockers. AF
indicates atrial fibrillation; BMI, body mass index; HF, heart failure; HR, heart
rate; NHYA, New York Heart Association; SBP, systolic blood pressure; and TIA,
TIA, transient ischemic attack.
2
Tavazzi et al Outcomes of Acute and Chronic Heart Failure 479
The comprehensive and robust risk stratification models for
in-hospital mortality from the Acute Decompensated Heart
Failure National Registry (ADHERE) and Organized Program
to Initiate Lifesaving Treatment in Hospitalized Patients with
Heart Failure (OPTIMIZE-HF) data bases3,6 did not include
a long-term follow-up. One study published recently, dealing with AHF patients,20 included 1-year follow-up and gives
similar results compared with those of the present study. This
survey was conducted in 30 European countries and its main
drawbacks are the limited representativeness of the participating countries and a rate of 13% patients lost to follow-up. In
contrast, the main limitation of the present study is that of
being a single country registry, with the advantages of a better
compliance to follow-up and a good representativeness of the
country’s cardiology network. At the end, the similarity of the
findings of both studies reinforces each other.
Downloaded from http://circheartfailure.ahajournals.org/ by guest on May 3, 2017
CHF Patients
Differently from the AHF domain, crowded by observational
studies but poor of successful randomized controlled trials, in
CHF domain large randomized controlled trials, mostly successful, have been performed,20–22 while few systematic observational studies have been reported. The present study shows
3 important findings. First, the recommended pharmacological treatments were incorporated into clinical practice and
maintained over time. Second, the progressive nature of CHF
looks relatively controlled with an annual mortality rate <6%
(two third for cardiovascular causes). Third, several independent predictors of poor medium-term outcome have been
identified. Among them, low systolic BP and low body weight
are confirmed as alarming signals, together with severe mitral
regurgitation, anemia, renal dysfunction, and a large QRS.
High heart rate also emerged as an important marker of risk
with a 2% increase in the probability of death within 1 year
per 1 incremental heart beat. However, it is noteworthy that
in our population, as in other studies,23,24 only 41% of deaths
occurring during the follow-up were because of HF. Accordingly, in CHF, with advancing age, the concept of risk should
be extended to a variety of comorbid conditions in a holistic
view of the patients.
The findings of the decreased risk associated with β-blocker
treatment and the increased risk of digitalis therapy should be
considered with great caution. In the daily practice, β-blockers
are prescribed more frequently in patients with less severe
HF,25 whereas digitalis is mostly given to patients resistant to
other recommended therapy or in atrial fibrillation.
Limitations
Some important limitations of our survey must be acknowledged. First, although criteria for HF diagnosis were thoroughly
discussed during the investigator meetings and the guidelines
for HF diagnosis and treatment were commented on and distributed to all investigators, the diagnosis of HF remained at the
discretion of the investigators based on their clinical judgment
and without a central validation. Second, patients lost to follow-up were ≈3% for their vital status and ≈5% for their hospitalizations. This performance is suboptimal for a controlled
study but in our view is acceptable for an observational study.
Third, all enrolling centers were monitored with periodic visits
by trained professionals of the coordinating center of the study,
but a log of out- and inpatients admitted to the wards and clinics of the enrolling hospitals was not available. Accordingly,
we cannot prove the consecutiveness of patients’ enrollment.
Fourth, patients were enrolled in cardiology wards and clinics,
not including those presenting at the emergency department, or
admitted to other hospital facilities. Accordingly, the population reported in this article does not represent the universe of
HF patients. Fifth, the ascertainment of cause of death was not
adjudicated by a formal committee.
Conclusions
Although death rate of patients with CHF seems to slowly
improve over time,26–28 outcomes’ rates of patients admitted
for AHF are still very high in-hospital, and for several months
after discharge. The in-hospital therapeutic approach to these
patients has practically remained unchanged during the last
decades and it is poorly effective. The therapeutic maintenance after discharge, able to control the disease progression
in chronic phase, does not seem to work enough in the postacute phase. The outcomes’ predictors in both AHF and CHF
in a representative Western country population have been
defined.
Appendix
Steering Committee
L. Tavazzi (Chairman), G. Cacciatore, A. Chinaglia, A. Di Lenarda,
A.P. Maggioni, A. Mortara, M. Metra, F. Oliva, and M. Senni.
Coordinating Center
ANMCO (Italian Association of Hospital Cardiologists) Research
Center (A.P. Maggioni, M. Gorini, I. Cangioli, L. Gonzini, D. Lucci,
and L. Sarti).
Participating Centers and Investigators
Acerra (L. Ferrara); Albano Laziale (P. Midi, A. Felici, G. Pajes);
Ancona (D. Gabrielli, A. Moraca); Aosta (G. Begliuomini, M.
Sicuro); Ascoli Piceno (L. Moretti, G. Gregori); Benevento (D.
Raucci, M. Scherillo); Bergamo, Ospedali Riuniti, U.C. Medicina
Cardiovascolare (M. Gori, A. Fontana, M. Senni); Bergamo, Ospedali
Riuniti, USC. Di Cardiologia (A. Grosu, A. Gavazzi); Brescia (R.
Danesi); Bussolengo (A.M. Anselmi); Casarano (S. Ciricugno, C.
Perrone, G. Piccinni); Castellammare Di Stabia (R. Longobardi);
Catania (G. Arcidiacono, S. Felis); Conegliano (C. Marcon, P.
Delise); Cosenza (G. Misuraca,F. Fascetti); Empoli (F. Venturi, A.
Brandinelli Geri, A. Zipoli); Firenze, AOU Careggi (S. Valente, C.
Giglioli, G. Gensini); Firenze, San Giovanni Di Dio (C. Minneci,
G. Santoro); Garbagnate Milanese (F. Locati, S. Pardea); Legnano
(C. Inserra, S. De Servi); Lumezzane (E. Zanelli, A. Giordano);
Manduria (V. Russo); Merate (G. Lecchi, B. Riva, S. Maggiolini);
Milano, Ospedale Niguarda, Cardiologia 2 (A. Verde, C. Vittori);
Milano, Ospedale Niguarda, UO Attivita’ Ambulatorio Villa Marelli
(E. Giagnoni, A. Sachero, A. Alberti); Milazzo (C. Coppolino, L.
Vasquez); Montescano (G. Guazzotti, O. Febo); Monza, San Gerardo
(A. Ciro’, A. Vincenzi, A. Grieco); Monza, Policlinico di Monza (A.
Mortara, E. D’Elia); Napoli, AO Monaldi, Cardiologia Riabilitativa (D.
Miceli); Napoli, AO Monaldi, UOC Cardiologia (S. Padula); Napoli,
Incurabili (S. Luca’, N. Armogida); Orbassano (L. Montagna, G.
Bonfiglio, R. Pozzi); Palermo, AOR Villa Sofia-Cervello PO Cervello
(G. Celona, A. Floresta, A. Canonico); Palermo, AOR Villa SofiaCervello PO Villa Sofia (V. Cirrincione, F. Ingrilli’, N. Sanfilippo);
Palmanova (R. Gortan, M. Baldin); Passirana-Rho (A. Frisinghelli,
M. Veniani); Pavia (L. Scelsi, L. Oltrona Visconti); Pescia (G. Italiani,
480 Circ Heart Fail May 2013
W. Vergoni); Piedimonte Matese (L. De Risi, R. Battista); Poggibonsi
(M. Romei); Pordenone (R. Piazza); Ravenna (G. Bellanti, G. Ricci
Lucchi, M. Margheri); Reggio Calabria (G. Pulitano’, A. Ruggeri);
Roma, AO San Giovanni Addolorata (G. Cacciatore, N. Pagnoni, A.
Boccanelli); Roma, INRCA (D. Del Sindaco, M. Cangelosi); Roma,
San Camillo (G. Pulignano, M. Pulcini, M. Fera); San Bonifacio (E.
Carbonieri, M. Tinto, M. Anselmi); San Pietro Vernotico (A. Renna);
Sarzana - Loc. S. Caterina (D. Bertoli, R. Petacchi); Sassari (F. Uras);
Scorrano (O. De Donno, E. De Lorenzi); Siracusa (C. Rubera, E.
Mossuti); Soriano Calabro (L. Anastasio); Teramo (L. Piccioni, C.
Napoletano); Terni (M. Bernardinangeli, G. Proietti); Trieste (M.
Merlo, M. Moretti, G. Sinagra); Vasto (G. Levantesi); Verbania (S.
Randazzo); Veruno (A. Mezzani); and Vibo Valentia (L. Anastasio).
Sources of Funding
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The sponsor of the study was the Heart Care Foundation (Fondazione
Italiana per la Lotta alle Malattie Cardiovascolari), a nonprofit independent institution which is also the owner of the database. Database
management, quality control of the data, and data analyses were under
the responsibility of the Research Center of the Italian Association of
Hospital Cardiologists (ANMCO). The study was partially supported
by an unrestricted grant by Novartis, Abbott, and Medtronic, Italy.
No fees were provided to either cardiology centers or investigators. No compensation was provided to the members of the Steering
Committee. 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.
Disclosures
Dr Tavazzi has received research grants from Boston Scientific and
Vifor Pharma, has participated in speaker bureaus and advisory
boards for Servier. Dr Metra has participated in speaker bureaus for
Novartis and Servier, advisory boards for Novartis, Bayer and honoraria from Abbott Vascular, Bayer, Corthera, Novartis, and Servier.
Marco Gorini is an employee of Heart Care Foundation, which conducted the study with an unresctricted grant of research from Novartis,
Abbott, and Medtronic. Dr Maggioni is an employee of Heart Care
Foundation, which conducted the study with an unresctricted grant
from Novartis, Abbott, and Medtronic and has been a consultant for
Novartis, Amgen, and Bayer. The other authors have no conflicts to
report.
References
1. O’Connor CM, Stough WG, Gallup DS, Hasselblad V, Gheorghiade M.
Demographics, clinical characteristics, and outcomes of patients hospitalized for decompensated heart failure: observations from the IMPACTHF registry. J Card Fail. 2005;11:200–205.
2.Rudiger A, Harjola VP, Müller A, Mattila E, Säila P, Nieminen M,
Follath F. Acute heart failure: clinical presentation, one-year mortality
and prognostic factors. Eur J Heart Fail. 2005;7:662–670.
3. Adams KF Jr, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR,
Abraham WT, Berkowitz RL, Galvao M, Horton DP; ADHERE Scientific
Advisory Committee and Investigators. Characteristics and outcomes of
patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100 000 cases in the
Acute Decompensated Heart Failure National Registry (ADHERE). Am
Heart J. 2005;149:209–216.
4. Lee DS, Austin PC, Rouleau JL, Liu PP, Naimark D, Tu JV. Predicting
mortality among patients hospitalized for heart failure: derivation and
validation of a clinical model. JAMA. 2003;290:2581–2587.
5. Zannad F, Mebazaa A, Juillière Y, Cohen-Solal A, Guize L, Alla F, Rougé
P, Blin P, Barlet MH, Paolozzi L, Vincent C, Desnos M, Samii K; EFICA
Investigators. Clinical profile, contemporary management and one-year
mortality in patients with severe acute heart failure syndromes: The
EFICA Study. Eur J Heart Fail. 2006;8:697–705.
6.Abraham WT, Fonarow GC, Albert NM, Stough WG, Gheorghiade
M, Greenberg BH, O’Connor CM, Sun JL, Yancy CW, Young JB;
OPTIMIZE-HF Investigators and Coordinators. Predictors of in-hospital mortality in patients hospitalized for heart failure: insights from the
Organized Program to Initiate Lifesaving Treatment in Hospitalized
Patients with Heart Failure (OPTIMIZE-HF). J Am Coll Cardiol.
2008;52:347–356.
7. Cleland JG, Swedberg K, Follath F, Komajda M, Cohen-Solal A, Aguilar
JC, Dietz R, Gavazzi A, Hobbs R, Korewicki J, Madeira HC, Moiseyev
VS, Preda I, van Gilst WH, Widimsky J, Freemantle N, Eastaugh J,
Mason J; Study Group on Diagnosis of the Working Group on Heart
Failure of the European Society of Cardiology. The EuroHeart Failure
survey programme: a survey on the quality of care among patients with
heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur
Heart J. 2003;24:442–463.
8. Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-Solal
A, Dietz R, Gavazzi A, Van Gilst WH, Hobbs R, Korewicki J, Madeira
HC, Moiseyev VS, Preda I, Widimsky J, Freemantle N, Eastaugh J,
Mason J; Study Group on Diagnosis of the Working Group on Heart
Failure of the European Society of Cardiology. The EuroHeart Failure
Survey programme: a survey on the quality of care among patients with
heart failure in Europe. Part 2: treatment. Eur Heart J. 2003;24:464–474.
9. Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola
VP, Hochadel M, Komajda M, Lassus J, Lopez-Sendon JL, Ponikowski
P, Tavazzi L; EuroHeart Survey Investigators; Heart Failure Association,
European Society of Cardiology. EuroHeart Failure Survey II (EHFS II):
a survey on hospitalized acute heart failure patients: description of population. Eur Heart J. 2006;27:2725–2736.
10. Krantz MJ, Ambardekar AV, Kaltenbach L, Hernandez AF, Heidenreich
PA, Fonarow GC; Get With the Guidelines Steering Committee and
Hospitals. Patterns and predictors of evidence-based medication continuation among hospitalized heart failure patients (from Get With the
Guidelines-Heart Failure). Am J Cardiol. 2011;107:1818–1823.
11. Tavazzi L, Maggioni AP, Lucci D, Cacciatore G, Ansalone G, Oliva F,
Porcu M; Italian survey on Acute Heart Failure Investigators. Nationwide
survey on acute heart failure in cardiology ward services in Italy. Eur
Heart J. 2006;27:1207–1215.
12.Siirila-Waris K, Lassus J, Melin J, Peuhkurinen K, Nieminem MS,
Harjola VP. FINN-AKVA Study Group. Characteristics, outcomes, and
predictors of 1-year mortality in patients hospitalized for acute heart failure. JAMA. 2006;296:2217–2226.
13. Harjola VP, Follath F, Nieminen MS, Brutsaert D, Dickstein K, Drexler
H, Hochadel M, Komajda M, Lopez-Sendon JL, Ponikowski P, Tavazzi
L. Characteristics, outcomes, and predictors of mortality at 3 months and
1 year in patients hospitalized for acute heart failure. Eur J Heart Fail.
2010;12:239–248.
14. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski
P, Poole-Wilson PA, Strömberg A, van Veldhuisen DJ, Atar D, Hoes
AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K; ESC
Committee for Practice Guidelines (CPG). ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task
Force for the diagnosis and treatment of acute and chronic heart failure
2008 of the European Society of Cardiology. Developed in collaboration
with the Heart Failure Association of the ESC (HFA) and endorsed by
the European Society of Intensive Care Medicine (ESICM). Eur J Heart
Fail. 2008;10:933–989.
15. Oliva F, Mortara A, Cacciatore G, Chinaglia A, Di Lenarda A, Gorini
M, Metra M, Senni M, Maggioni AP, Tavazzi L; IN-HF Outcome
Investigators. Acute heart failure patient profiles, management and
in-hospital outcome: results of the Italian Registry on Heart Failure
Outcome. Eur J Heart Fail. 2012;14:1208–1217.
16. Abrahamsson P, Dobson J, Granger CB, McMurray JJ, Michelson EL,
Pfeffer M, Pocock S, Solomon SD, Yusuf S, Swedberg K; CHARM
Investigators. Impact of hospitalization for acute coronary events on
subsequent mortality in patients with chronic heart failure. Eur Heart J.
2009;30:338–345.
17.Cotter G, Metra M, Weatherley BD, Dittrich HC, Massie BM,
Ponikowski P, Bloomfield DM, O’Connor CM. Physician-determined
worsening heart failure: a novel definition for early worsening heart
failure in patients hospitalized for acute heart failure–association with
signs and symptoms, hospitalization duration, and 60-day outcomes.
Cardiology. 2010;115:29–36.
18.Metra M, Teerlink JR, Felker GM, Greenberg BH, Filippatos G,
Ponikowski P, Teichman SL, Unemori E, Voors AA, Weatherley BD,
Cotter G. Dyspnoea and worsening heart failure in patients with acute
heart failure: results from the Pre-RELAX-AHF study. Eur J Heart Fail.
2010;12:1130–1139.
19. O’Connor CM, Mentz RJ, Cotter G, Metra M, Cleland JG, Davison BA,
Givertz MM, Mansoor GA, Ponikowski P, Teerlink JR, Voors AA, Fiuzat
M, Wojdyla D, Chiswell K, Massie BM. The PROTECT in-hospital risk
Tavazzi et al Outcomes of Acute and Chronic Heart Failure 481
model: 7-day outcome in patients hospitalized with acute heart failure
and renal dysfunction. Eur J Heart Fail. 2012;14:605–612.
20. Maggioni AP, Dahlström U, Filippatos G, Chioncel O, Leiro MC, Drozdz
J, Fruhwald F, Gullestad L, Logeart D, Metra M, Parissis J, Persson H,
Ponikowski P, Rauchhaus M, Voors A, Nielsen OW, Zannad F, Tavazzi L;
Heart Failure Association of ESC (HFA). EURObservational Research
Programme: the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart
Fail. 2010;12:1076–1084.
21.Fonarow GC, Albert NM, Curtis AB, Stough WG, Gheorghiade M,
Heywood JT, McBride ML, Inge PJ, Mehra MR, O’Connor CM,
Reynolds D, Walsh MN, Yancy CW. Improving evidence-based care
for heart failure in outpatient cardiology practices: primary results
of the Registry to Improve the Use of Evidence-Based Heart Failure
Therapies in the Outpatient Setting (IMPROVE HF). Circulation.
2010;122:585–596.
22. Chan PS, Oetgen WJ, Buchanan D, Mitchell K, Fiocchi FF, Tang F, Jones
PG, Breeding T, Thrutchley D, Rumsfeld JS, Spertus JA. Cardiac performance measure compliance in outpatients: the American College of
Cardiology and National Cardiovascular Data Registry’s PINNACLE
(Practice Innovation And Clinical Excellence) program. J Am Coll
Cardiol. 2010;56:8–14.
23. Dunlay SM, Redfield MM, Weston SA, Therneau TM, Hall Long K,
Shah ND, Roger VL. Hospitalizations after heart failure diagnosis a community perspective. J Am Coll Cardiol. 2009;54:1695–1702.
24. Henkel DM, Redfield MM, Weston SA, Gerber Y, Roger VL. Death in
heart failure: a community perspective. Circ Heart Fail. 2008;1:91–97.
25. Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A,
Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes
in chronic heart failure (SHIFT): a randomised placebo-controlled study.
Lancet. 2010;376:875–885.
26. Jhund PS, Macintyre K, Simpson CR, Lewsey JD, Stewart S, Redpath A,
Chalmers JW, Capewell S, McMurray JJ. Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003:
a population study of 5.1 million people. Circulation. 2009;119:515–523.
27. Schaufelberger M, Swedberg K, Köster M, Rosén M, Rosengren A.
Decreasing one-year mortality and hospitalization rates for heart failure
in Sweden; Data from the Swedish Hospital Discharge Registry 1988 to
2000. Eur Heart J. 2004;25:300–307.
28. Senni M, De Maria R, Gregori D, Gonzini L, Gorini M, Cacciatore G,
Gavazzi A, Pulignano G, Porcu M, Maggioni AP. Temporal trends in
survival and hospitalizations in outpatients with chronic systolic heart
failure in 1995 and 1999. J Card Fail. 2005;11:270–278.
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CLINICAL PERSPECTIVE
In consideration of the limitations of available surveys and registries of heart failure (HF) patients, a nationwide registry was
performed with the aim to include both acute and chronic heart failure patients, representative of the current HF population
complexity balanced with respect to the Italian hospital population samples. From November 2007 to December 2009, 5610
HF patients were enrolled, 3755 were ambulatory patients with chronic heart failure and 1855 were patients admitted for
acute heart failure (797 with de novo HF and 1058 with worsening HF). Although the death rate of patients with chronic
heart failure slowly diminished over time, the adverse outcome rates of patients admitted for acute heart failure were still
very high in-hospital, and also for several months after discharge. The in-hospital therapeutic approach to these patients has
remained essentially unchanged during the last decades, in contrast to the advances for those with chronic heart failure. The
still unacceptably high rate of death of patients hospitalized for acute heart failure clearly calls for therapeutic progress in
that area. The therapeutic maintenance or optimization of evidence-based treatments after discharge, effective in controlling
disease progression and favorably impacting the outcome of patients with chronic heart failure, does not seem to be as effective in the postacute heart failure phase.
Downloaded from http://circheartfailure.ahajournals.org/ by guest on May 3, 2017
Multicenter Prospective Observational Study on Acute and Chronic Heart Failure:
One-Year Follow-up Results of IN-HF (Italian Network on Heart Failure) Outcome
Registry
Luigi Tavazzi, Michele Senni, Marco Metra, Marco Gorini, Giuseppe Cacciatore, Alessandra
Chinaglia, Andrea Di Lenarda, Andrea Mortara, Fabrizio Oliva and Aldo P. Maggioni
Circ Heart Fail. 2013;6:473-481; originally published online March 8, 2013;
doi: 10.1161/CIRCHEARTFAILURE.112.000161
Circulation: Heart Failure is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX
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