European Heart Journal (2002) 23, 1692–1698
doi:10.1053/euhj.2001.3157, available online at http://www.idealibrary.com on
Cumulative effect of complete left bundle-branch
block and chronic atrial fibrillation on 1-year mortality
and hospitalization in patients with congestive
heart failure
A report from the Italian network on congestive heart failure
(in-CHF database)
S. Baldasseroni1, L. De Biase2, C. Fresco3, N. Marchionni4, M. Marini1,
G. Masotti4, G. Orsini1, M. Porcu5, F. Pozzar6, M. Scherillo7 and A. P. Maggioni1 on
behalf of the Italian Network on Congestive Heart Failure (IN-CHF) Investigators
1
Italian Association of Hospital Cardiologists (ANMCO) Research Center, Florence, Italy; 2S. Andrea Hospital,
Department of Cardiology, Rome, Italy; 3S.M. Misericordia Hospital, Department of Cardiology, Udine, Italy;
4
Department of Critical Care Medicine and Surgery, Section of Gerontology and Geriatric Medicine, University of
Florence, Azienda Ospedaliera Gareggi, Florence, Italy; 5S. Michele Brotzu Hospital, Department of Cardiology,
Cagliari, Italy; 6S. Camillo Hospital, Department of Cardiology, Rome, Italy; 7Monaldi Hospital, Department of
Cardiology, Naples, Italy
Background Many clinical variables have been proposed
as prognostic factors in patients with congestive heart
failure. Among these, complete left bundle-branch block
and atrial fibrillation are known to impair significantly left
ventricular performance in patients with congestive heart
failure. However, their combined effect on mortality has
been poorly investigated. The aim of this study was to
determine whether left bundle-branch block associated with
atrial fibrillation had an independent, cumulative effect on
mortality for congestive heart failure.
Methods and Results We analysed the Italian Network
on congestive heart failure (IN-CHF) Registry that was
established by the Italian Association of Hospital Cardiologists in 1995. One-year follow-up data were available for
5517 patients. Complete left bundle-branch block and atrial
fibrillation were associated in 185 (3·3%) patients. In this
population the cause of congestive heart failure was dilated
cardiomyopathy (38·4%), ischaemic heart disease (35·1%),
hypertensive heart disease (17·3%), and other aetiologies
(9·2%). This combination of electrical defects was
associated with an increased 1-year mortality from any
cause (hazard ratio, HR: 1·88; 95% CI 1·37–2·57) and
sudden death (HR: 1·89; 95% CI 1·17–3·03) and 1-year
hospitalization rate (HR: 1·83; 95% CI 1·26–2·67).
Conclusions In patients with congestive heart failure, the
contemporary presence of left bundle-branch block and
atrial fibrillation was associated with a significant increase
in mortality. This synergistic effect remained significant
after adjusting for clinical variables usually associated with
advanced heart failure. We can conclude that this combination of electrical disturbances identifies a congestive heart
failure specific population with a high risk of mortality.
(Eur Heart J, 2002; 23: 1692–1698, doi:10.1053/euhj.2001.
3157)
2002 The European Society of Cardiology. Published by
Elsevier Science Ltd. All rights reserved.
Key Words: Congestive heart failure, atrial fibrillation,
complete left bundle branch-block, prognosis
Revision submitted 19 December 2001, and accepted 19 December 2001.
The IN-CHF Registry was supported in part by Merck Sharp & Dohme Italy.
See the Appendix for a complete list of participating centres and Investigators.
Correspondence: Aldo P. Maggioni, MD, ANMCO Research Center, Via La Marmora 34, 50121 Florence, Italy.
0195-668X/02/$35.00
2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.
Left bundle-branch block associated with atrial fibrillation in CHF patients
Introduction
In the last few years, total mortality from heart disease
has been declining in industrialized countries as a consequence of improved treatment and primary prevention[1], but the number of patients affected by congestive
heart failure is still increasing[1]. This is caused by
increasing life-expectancy and the age-associated prevalence of heart diseases in general, and of congestive heart
failure in particular[2–4].
Several clinical and pathophysiological factors have
been proposed as independent prognostic indicators in
patients with congestive heart failure[5–9].
Recently, data concerning the prognostic significance
of intraventricular conduction defects and, in particular,
of complete left bundle-branch block in congestive heart
failure, have also been evaluated[10].
The role of atrial fibrillation in heart failure is still
debated. Indeed while there is a strong consensus about
the dramatic effect of atrial fibrillation on the haemodynamic profile of patients affected by heart failure[11],
its prognostic effect is still under discussion. Data on the
prognostic value of atrial fibrillation in congestive heart
failure are somewhat conflicting[12,13].
Therefore, we analysed the IN-CHF database on
unselected outpatients with congestive heart failure of
different aetiologies, followed-up for 1 year by a large
number of cardiology centres in Italy, with the purpose
of evaluating the prevalence of the association of left
bundle-branch block with atrial fibrillation and testing
whether this association is characterized by higher
mortality and hospitalization rates independently of all
other variables.
1693
cardiologist at each participating centre, using a standardized format outlined in the database. This information was used by the computer programme to control
for the acceptability of the diagnosis of left bundlebranch block, and to distinguish between incomplete
(QRS duration 100–120 ms) and complete (QRS duration d120 ms) associated with morphological criteria
block. Patients were followed-up according to the routine clinical practice of the participating centres. In this
context, patients underwent standard chest X-ray, 24-h
Holter ECG monitoring to confirm the presence of
chronic atrial fibrillation, two-dimensional echocardiography, and blood sampling for the most common laboratory tests (e.g. creatinine, electrolytes, etc.), when the
attending cardiologists deemed them necessary. Cardiologists at the participating centres were responsible for
confirming the contemporary presence of complete left
bundle-branch block and atrial fibrillation, for defining
the aetiology of congestive heart failure and the NYHA
class, reporting that the third heart sound was audible,
and computing the cardiothoracic ratio. The left ventricular ejection fraction was calculated from the fourchamber apical echocardiographic view. Ventricular
tachycardia was defined as an episode of tachycardia
with a widened QRS that lasted longer than three beats,
with a heart rate >100 beats . min 1, as revealed by
24-h Holter ECG monitoring. Renal dysfunction was
defined as a serum creatinine >2·5 mg . dl 1. Previous
hospitalizations for congestive heart failure in the year
before entry were also recorded. After the baseline visit,
patients were followed-up for at least 1-year. In cases
of out-of-hospital death, the event was confirmed by
telephone interview with the patient’s relatives, using a
standard questionnaire aimed at determining the mode
of death (sudden vs non-sudden).
Methods
Study design, collected data and definitions
Data for the present analysis originated from the database of the IN-CHF Registry[14], a survey designed by an
ad-hoc Committee of the Italian Association of Hospital
Cardiologists (ANMCO, Florence, Italy) in 1995. Onehundred and fifty cardiology centres agreed to participate in the study. While the centres were distributed
across the whole country, they were more frequently
located in northern (46%) than in central (24%) or
southern (30%) Italy, representing the spread of cardiology centres in Italy. Training sessions were organized
to prepare clinicians to collect and enter data using an
ad-hoc designed software. Patients’ data were recorded
at each centre by trained cardiologists and were then
pooled into a single database at the ANMCO Research
Center. Entry into the database required that patients
had a diagnosis of congestive heart failure based on the
ESC guidelines[15]. Demographic, clinical, instrumental
and laboratory variables, and information on drug
therapy were collected for each patient. At baseline, a
12-lead ECG was recorded and coded by a single
Study population
Between March 1995 and January 2000 a total of 6284
consecutive patients with congestive heart failure completed the 1-year follow-up. Of these 767 (706 affected by
congestive heart failure due to primary valvular heart
disease and 61 patients underwent heart transplantation)
were excluded from the present analysis which includes
therefore 5517 patients.
Statistical analysis
Data were analysed using the SAS statistical package.
Continuous variables are presented as meanstandard
deviation. The chi-square test was used to test the
association of complete left bundle-branch block/atrial
fibrillation with several baseline characteristics and
1-year total mortality. Cox proportional hazards multivariate models with calculation of the adjusted hazard
ratio and 95% confidence intervals (95% CI) were used
to identify the independent determinants of all-cause
Eur Heart J, Vol. 23, issue 21, November 2002
1694
S. Baldasseroni et al.
Table 1 Demographic and clinical characteristics of the four groups of patients according to the presence of left
bundle-branch block (LBBB) or atrial fibrillation (AF) or both: absence of left bundle-branch block and atrial
fibrillation (group A) presence of complete left bundle-branch block (group B), presence of atrial fibrillation (group
C), presence of atrial fibrillation and complete left bundle-branch block (group D)
A
B
C
D
(no AF, no LBBB) (no AF, LBBB) (AF, no LBBB) (AF and LBBB) P value
(%)
(%)
(%)
(%)
Sex (male)
Age >70 years
NYHA III–IV
Ischaemic heart disease
Previous hospitalization for chronic heart failure
Third heart sound
Ejection fraction <30%
Systolic blood pressure <100 mmHg
Cardiothoracic ratio >55
Creatinine >2·5 mg . dl 1
Ventricular tachycardia
ACE-inhibitors
Beta-blockers
79·3
28·8
23·9
53·3
53·1
22·7
30·5
2·7
52·2
30·5
27·1
83·6
20·4
mortality and of mortality due to sudden death.
A two-tailed P<0·05 was considered statistically
significant.
Results
The study population of 5517 patients had a mean age of
6312 years (range 14–96 years), included 1295 (23·5%)
women and 1544 (28·0%) cases of NYHA class III–IV
congestive heart failure. The 767 patients with complete
1-year follow-up data who were excluded from the
present analysis were of similar age (6512 years; range
17–91 years), with a larger prevalence of women (38·6%,
P<0·01) and of NYHA class III–IV congestive heart
failure (38·8%, P<0·01).
Complete left bundle-branch block and atrial
fibrillation: prevalence and associated
clinical characteristics
Of the 5517 patients included in the present analysis,
3328 (60·3%) had neither left bundle-branch block nor
atrial fibrillation (group A), 1206 (21·9%) had an isolated complete left bundle-branch block (group B), 798
(14·5%) had an isolated chronic atrial fibrillation (group
C), and 185 (3·3%) had complete left bundle-branch
block associated with chronic atrial fibrillation (group
D). The demographic and clinical characteristics of the
four groups are reported in Table 1.
Group D patients were more frequently males and, as
a probable result of the presence of chronic atrial
fibrillation, group C and D patients were older than
those in the other two groups. Patients in group D
presented a greater reduction in functional capacity as
assessed by NYHA classification, and more significant
Eur Heart J, Vol. 23, issue 21, November 2002
69·1
27·7
30·9
33·5
54·8
30·5
49·9
3·3
62·4
49·9
28·2
79·6
13·4
75·2
43·7
36·5
33·3
59·4
20·1
29·6
2·8
67·6
29·6
37·0
87·6
17·2
81·6
44·7
44·9
35·4
67·0
31·9
44·7
7·6
67·6
44·7
30·4
86·5
9·2
0·001
0·001
0·001
0·001
0·001
0·001
0·001
0·001
0·005
0·033
ns
0·001
0·001
clinical impairment as demonstrated by the higher rate
of patients with a third heart sound, previous hospitalization for congestive heart failure, hypotension and
cardiac enlargement. Groups D and B had more severe
left ventricular dysfunction and a higher rate of renal
dysfunction. The prevalence of ventricular tachycardia
was similar across the four groups. A high proportion of
patients presented in each group had been hospitalized
for congestive heart failure in the previous year, and this
proportion was highest in group D. The prevalence
of ischaemic heart disease was significantly higher in
group A.
ECG abnormalities and prognosis
Overall, 659/5517 (11·9%) patients died over the 1-year
follow-up, with almost half the deaths (n=306) being
classified as sudden. All-cause mortality and mortality
due to sudden death was significantly higher among
patients with any of the two ECG abnormalities and was
highest when these were associated than in the other
three groups (Fig. 1). Indeed the contemporary presence
of left bundle-branch block and atrial fibrillation was
associated with 26·5% 1-year all-cause mortality (unadjusted RR 6·11, 95% CI 3·76–9·90) being 11·2% of
all deaths classified as sudden death and 15·3% as
non-sudden mortality.
Similarly, the prevalence of hospital admissions during follow-up (Fig. 2) was significantly higher in groups
B and C than in group A and highest (28·1%) in group D
(unadjusted RR 1·83, 95% CI 1·26–2·67).
Further analyses were then carried out to predict the
adjusted hazard ratio for all-cause death and sudden
death at 1 year. In these models, we entered all the
variables that in univariate analyses (data not shown)
were associated with all-cause mortality (Table 2). Age,
Left bundle-branch block associated with atrial fibrillation in CHF patients
1695
effect and, on average, it was estimated to increase the
risk of all-cause death at 1 year by 85% (Table 2, Fig. 1).
The same variables, with the exclusion of renal failure,
were significantly associated with the risk of sudden
death at 1 year (Table 3). Also in this multivariate model
the contemporary presence of left bundle-branch block
and atrial fibrillation was an independent predictor of
the risk of sudden death, that was increased by 86%
when both ECG abnormalities were present.
Discussion
Figure 1 One-year total mortality and sudden death
in patients without complete left bundle-branch block
(LBBB) and chronic atrial fibrillation (AF) (group A),
with isolated left bundle-branch block (group B), with
isolated chronic atrial fibrillation (group C) and simultaneous presence of complete left bundle-branch block and
atrial fibrillation (group D).
Relative risk of all-cause
P < 0·001
28·1
30
25
%
A
Unadjusted 1
21·9 21·7
B
C
D
1·23 1·21 1·83
(1·01– (1·03– (1·26–
1·49) 1·43) 2·67)
20·1
20 18·7
15
10
Other causes of
hospitalization
Hospitalization for HF
0
AF:
LBBB:
A
–
–
B
–
+
C
+
–
D
+
+
Total
population
5
Figure 2 One-year hospitalization for all-cause and for
heart failure (HF) in patients without complete left
bundle-branch block (LBBB) and chronic atrial fibrillation
(AF) (group A), with isolated left bundle-branch block
(group B), with isolated chronic atrial fibrillation (group
C) and simultaneous presence of complete left bundlebranch block and atrial fibrillation (group D).
heart rate and systolic blood pressure were entered as
continuous variables while all the other variables presented in the two tables were entered as dichotomous
variables.
The risk of all-cause death at 1 year was significantly
increased with advancing age and in the presence of
ischaemic heart disease, previous hospitalization for
congestive heart failure, and several indicators of disease
severity or co-morbidity such as NYHA class III–IV,
reduced systolic blood pressure, third heart sound,
ventricular tachycardia, and renal failure (Table 2).
However, even after adjusting for all these covariates,
the association of left bundle-branch block with atrial
fibrillation still retained its unfavourable prognostic
In the last few years, the prognosis of patients with
congestive heart failure was largely improved mainly
due to the widespread and increasing use of effective
therapies such as ACE-inhibitors, beta-blockers and
spironolactone[16–20].
However, morbidity and mortality still remain high,
suggesting the need to identify subgroups of patients
particularly, those at high risk, with the aim of individually tailoring pharmacological therapy or newer nonpharmacological therapeutic strategies, such as multisite
cardiac pacing[21].
In keeping with other recent studies, our analysis
demonstrated that atrial fibrillation and left bundlebranch block are useful clinical variables with which to
identify a population at higher risk of total and sudden
death in congestive heart failure[22,23]. In this study we
have demonstrated that these two electrical abnormalities have a cumulative, negative effect on the prognosis
of patients with congestive heart failure. A further
clinically relevant finding of our study was that patients
presenting with both left bundle-branch block and atrial
fibrillation have an increased risk not only of 1-year
total mortality but also of hospitalization, with the
consequent increase in the costs to the health care
system and the further deterioration of patients’ quality
of life.
The clinical and demographic profiles of patients with
atrial fibrillation and/or left bundle-branch block were
different from those of patients without these abnormalities. These patients are older and had several characteristics suggesting a higher degree of clinical and
functional impairment. It has been commonly acknowledged that older and sicker patients are often undertreated with evidence-based recommended therapies.
For example, advanced age has been shown to be an
independent predictor of a reduced prescription rate of
ACE-inhibitors or beta-blockers[24–26]. This finding,
which may only in part account for the age-associated
increase in co-morbidity, can have a dramatic effect on
prognosis[24,26].
In the last few years, multisite cardiac and in particular biventricular pacing, was tested and seemed to be
effective in treating patients with congestive heart failure
associated with a left intraventricular conduction delay.
In fact this strategy can improve cardiocirculatory functional reserve and patient’s perceived quality of life[27,28].
Eur Heart J, Vol. 23, issue 21, November 2002
1696
S. Baldasseroni et al.
Table 2 Multivariate predictors of 1-year all-cause death in patients with atrial
fibrillation or left bundle-branch block and in patients with complete left bundlebranch block associated with atrial fibrillation
Variable
HR
95% CI
P=
Age (years)#
Ischaemic heart disease (yes vs no)
Previous hospitalization for CHF (yes vs no)
NYHA (III–IV vs I–II)
Systolic blood pressure (mmHg)#
Third heart sound (yes vs no)
Ventricular tachycardia (yes vs no)
Renal failure (yes vs no)
LBBB or AF (yes vs no)
LBBB and AF (yes vs no)
ACE–inhibitors (yes vs no)
Beta–blockers (yes vs no)
1·02
1·25
1·75
1·93
0·99
1·42
1·76
1·66
1·32
1·85
0·82
0·75
1·01–1·03
1·05–1·47
1·46–2·09
1·64–2·27
0·98–0·99
1·21–1·68
1·28–2·42
1·06–2·60
1·11–1·56
1·35–2·53
0·68–0·99
0·58–0·96
0·0001
0·0103
0·0001
0·0001
0·0001
0·0001
0·0005
0·0268
0·0013
0·0001
0·0480
0·0248
HR=hazard ratio; #=introduced as continuous variables; AF=atrial fibrillation; LBBB=complete
left bundle-branch block. Variables excluded from the model (P>0·10): sex; cardiothoracic ratio;
left ventricular ejection fraction.
Table 3 Multivariate predictors of 1-year risk of sudden death in patients with atrial
fibrillation or left bundle-branch block and in patients with left bundle-branch block
associated with atrial fibrillation
Variable
HR
95% CI
P=
Age (years)#
Ischaemic heart disease (yes vs no)
Previous hospitalization for CHF (yes vs no)
NYHA (III–IV vs I–II)
Systolic blood pressure (mmHg)#
Third heart sound (yes vs no)
Ventricular tachycardia (yes vs no)
LBBB or AF (yes vs no)
LBBB and AF (yes vs no)
Beta–blockers
1·01
1·32
1·88
1·52
0·99
1·71
1·96
1·35
1·86
1·50
1·00–1·03
1·03–1·69
1·44–2·44
1·19–1·94
0·98–0·99
1·35–2·17
1·25–3·08
1·06–1·73
1·16–2·99
1·03–2·20
0·0100
0·0288
0·0001
0·0007
0·0007
0·0001
0·0034
0·0157
0·0105
0·0351
HR=hazard ratio; #=introduced as continuous variables; AF=atrial fibrillation; LBBB=complete
left bundle-branch block. Variables excluded from the model (P>0·10): sex; cardiothoracic ratio;
left ventricular ejection fraction; renal failure; ACE-inhibitors.
Recently Leclercq et al. have demonstrated that biventricular pacing stimulation was particularly effective
in patients with congestive heart failure and wide QRS
associated with atrial fibrillation[29].
Other perspectives for patients with left bundlebranch block and atrial fibrillation could derive from a
new kind of atrial stimulation. Padeletti et al. have
recently demonstrated that inter-atrial septum pacing,
after restoration sinus rhythm, reduces the incidence of
supraventricular arrhythmic episodes and in particular
the relapse of atrial fibrillation[30].
This new technique, in association with biventricular
resyncronization, could become, in the near future,
another possible method of reducing mortality in
patients presenting with both left bundle-branch block
and atrial fibrillation. However, the efficacy of this
approach in this regard needs to be confirmed by ad-hoc
clinical trials of adequate size, because its usefulness is
Eur Heart J, Vol. 23, issue 21, November 2002
only supported by preliminary results obtained in small
series of patients with ‘soft’ end-points.
Our epidemiological data might help identify, in the
large heterogeneity of congestive heart failure patients,
the small subgroup in which these new pacing techniques
might be specifically tested on relevant end-points such
as morbidity and mortality.
Another relevant finding derived from our study is
that we analysed the prognosis of patients who are often
excluded from randomized clinical trials in spite of
the fact that they represent a consistent part of the
congestive heart failure outpatient population with a
poor prognosis especially in the elderly.
In contrast to a recent study focused in the community setting[31], in our study left bundle-branch block
alone or associated with atrial fibrillation is also an
independent predictor of a poor prognosis in outpatients. This may have been the result of the strict
Left bundle-branch block associated with atrial fibrillation in CHF patients
definition of a wide QRS in our study (QRS >120 ms
associated with morphological characteristics) in respect
of the study by Farwell et al.[31]. Our study also shows
that atrial fibrillation alone is likely to be an independent predictor of all-cause deaths in patients affected by
congestive heart failure.
Some limitations of our study must be acknowledged.
Due to the original purpose of the database used for this
analysis, examination of ECG measurements of QRS
duration was performed locally, albeit by a single,
trained cardiologist at each centre with subsequent
standardized, blinded methods and quality control techniques in a single core laboratories. Twenty-four hour
Holter monitoring to assess the presence of chronic
atrial fibrillation was analysed locally by the attending
cardiologist. Finally, the multivariate model was adjusted for clinical and demographic variables. With
respect to non-cardiac co-morbidities, the model was
adjusted only for renal failure, a limitation that becomes
particularly important if we consider that older patients
present commonly with an increased burden of concomitant non-cardiac diseases that may well affect their
overall prognosis.
In spite of these limitations, we believe that our
analysis provides information useful in identifying a
well-defined subgroup of patients at higher risk of death
and who deserve specific consideration and even more
aggressive treatments to improve their poor prognosis.
In this perspective our observations can represent the
rationale for future studies aimed at evaluating whether
ventricular resynchronization and restoration of sinus
rhythm can reduce such an increased risk of mortality.
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Appendix
Participating Centers and Investigators
Piemonte Borgomanero (A. Mezzani, M. Bielli); Cuneo (U.
Milanese, G. Ugliengo); Orbassano (R. Pozzi, F. Rabajoli);
Veruno (E. Bosimini); Valle d’Aosta Aosta (G. Begliuomini);
Lombardia Belgioioso (A. Ferrari, F. Barzizza); Bergamo (M. G.
Valsecchi, F. Dadda); Brescia (P. Faggiano); Cassano D’Adda (G.
Castiglioni, G. Gibelli); Chiari (A. L. Turelli); Como (R.
Belluschi); Cremona (C. Bianchi, C. Emanuelli); Desio
(S. Gramenzi, G. Foti); Erba Medicina (D. Agnelli); Esine (G.
Mascioli); Garbagnate Milanese (E. Cazzani); Gussago (E. Zanelli,
D. Domenighini); Legnano (C. Castelli); Mariano Comense (E.
Moroni); Milano Fondazione Don Gnocchi (E. Gara); Milano
Osp. Sacco Medicina (S. Guzzetti, S. Muzzupappa, M. Turiel, E.
Cappiello, G. Sandrone); Milano Osp. Niguarda II Cardiologia (F.
Recalcati); Milano Pio Albergo Trivulzio (D. Valenti); Monza (F.
Achilli, A. Vincenzi); Passirana (F. Rusconi, M. Palvarini); Pavia
Policlinico San Matteo (S. Ghio, A. Fontana, A. Giusti, L. Scelsi,
R. Sebastiani; M. Ceresa); Pavia I.I.A.A.R.R.S. Margherita (A.
Ferrari); Saronno (D. Nassiacos, S. Meloni); Seriate (T. Nicoli);
Sondalo (P. Bandini); Tradate Fondazione Maugeri (R. Pedretti,
M. Paolucci); Tradate Osp. Di Circolo Galmarini (L. Amati, M.
Ravetta); Varese Osp. Di Circolo (F. Morandi, S. Provasoli);
Varese Osp. Di Circolo Medicina (A. Bertolini, D. Imperiale, W.
Agen); Vizzolo Predabissi (E. Planca, P. Quorso); P. A. di Trento
Rovereto (A. Ferro); Rovereto Medicina (C. Pedrolli); Veneto
Belluno (P. Russo, L. Tarantini); Castelfranco Veneto (G.
Candelpergher); Conegliano Veneto (P. P. Cannarozzo); Feltre (F.
De Cian, A. Agnoli); Montebelluna (M. G. Stefanini); Padova (L.
Cacciavillani, G. M. Boffa); Pieve Di Cadore (L. Mario); Treviso
(G. Renosto, P. Stritoni); Vicenza (L. Varotto, M. Penzo);
Villafranca (G. Perini); Friuli Venezia Giulia Gorizia (G. Giuliano);
Monfalcone (E. Barducci); San Vito al Tagliamento (R. Piazza);
Udine Osp. S. M. della Misericordia (M. C. Albanese, C. Fresco);
Udine Casa di Cura (F. Picco, P. Venturini); Liguria Arenzano (A.
Camerini, R. Griffo); Genova Osp. Galliera (G. Derchi, L.
Delfino); Genova-Sestri Ponente (L. Pizzorno); Genova Osp. S.
Martino (S. Mazzantini, F. Torre); Rapallo (S. Orlandi); Sarzana
(D. Bertoli); Sestri Levante (A. Gentile); Emilia Romagna Bologna
Poliambulatorio Tiarini (F. Naccarella, M. Gatti, M. Coluccini);
Forlı̀ (G. Morgagni); Modena Osp. Sant’Agostino (G. Alfano);
Modena Policlinico (L. Reggianini, S. Sansoni); Parma (W. Serra);
Piacenza (F. Passerini); Riccione (P. Del Corso, L. Rusconi);
Eur Heart J, Vol. 23, issue 21, November 2002
Rimini (M. Marzaloni, M. Mezzetti), Scandiano (G. P.
Gambarati); Toscana Castelnuovo Garfagnana (P. R. Mariani, C.
Volterrani); Empoli (F. Venturi); Firenze Osp. S. M. Nuova (G.
Zambaldi); Firenze Osp. Nuovo S. Giovanni di Dio (G. Casolo);
Firenze Azienda Osp. Careggi (G. Moschi); Fucecchio (A. Geri
Brandinelli); Grosseto (G. Miracapillo); Lucca (A. Boni); Pescia
(G. Italiani, W. Vergoni); Pisa Osp. Santa Chiara (A. M. Paci);
Pontedera (F. Lattanzi, B. Reisenhofer); San Giovanni Valdarno
(D. Severini, T. Taddei); Viareggio (A. Dalle Luche, A. Comella);
Umbria Foligno (U. Gasperini); Gubbio (M. Cocchieri); Perugia
Monteluce (G. Alunni, E. Bosi, R. Panciarola); Spoleto
(G. Maragoni, G. Bardelli); Marche Ancona Osp. Sestilli (P.
Testarmata); Ancona Osp. Lancisi Centro Medicina Sociale
(L. Pasetti, A. Budini); Ancona Osp. Lancisi II Cardiologia (D.
Gabrilelli); Camerino (B. Coderoni); Lazio Albano Laziale (P.
Midi); Grottaferrata (C. Romaniello); Roma INRCA (D. Del
Sindaco, F. Leggio); Roma Osp. Forlanini (A. Terranova); Roma
Osp. San Camillo II Cardiologia (G. Pulignano); Roma Osp. San
Camillo Servizio (F. Pozzar); Roma Osp S. F. Neri (G. Ansalone,
B. Magris, P. Giannantoni); Roma Osp. S. Giovanni (G.
Cacciatore, G. Bottero, G. Scaffidi); Roma Osp. Sandro Pertini (C.
Valtorta, A. Salustri); Roma Osp. Sant’Eugenio (F. Amaddeo, G.
Barbato); Roma Osp. Santo Spirito (N. Aspromonte); Roma Osp.
Cristo Re (V. Baldo, E. Baldo); Abruzzo Popoli (C. Frattaroli, A.
Mariani); Vasto (G. Di Marco, G. Levantesi); Molise Larino (A. P.
Potena), Termoli (N. Colonna, A. Montano); Campania Napoli
Osp. Monaldi Medicina (P. Sensale, V. Rullo); Napoli Osp. S.
Gennaro (A. Somelli); Nola (F. Napolitano, P. Provvisiero);
Oliveto Citra (P. Bottiglieri); Puglia Bari Policlinico (N. Ciriello);
Brindisi (E. Angelini, C. Andriulo); Casarano (F. De Santis);
Francavilla Fontana (F. Cocco); Galatina Medicina (A. Zecca);
Gallipoli (A. Pennetta, F. Mariello); Lecce Osp. Fazzi (F. Magliari,
A. De Giorgi, M. Callerame); Mesagne (V. Santoro); San Pietro
Vernotico (S. Pede, A. Renna); Scorrano (O. De Donno, E. De
Lorenzi); Taranto Osp. SS. Annunziata (G. Polimeni, V. A.
Russo); Tricase (R. Mangia); Basilicata Policoro (L. Truncellito);
Calabria Belvedere Marittimo (F. P. Cariello); Catanzaro
Policlinico Servizio (M. Affinita); Catanzaro Policlinico Divisione
(F. Perticone, C. Cloro, D. Borelli); Cetraro (M. Matta, D.
Lopresti); Cosenza Osp. Dell’Annunziata (G. Misuraca, R.
Caporale); Cosenza Osp. Dell’Annunziata Medicina (P.
Chiappetta); Reggio Calabria Osp. Morelli (E. Tripodi, F.
Tassone); Rossano (S. Salituri); Siderno (C. Errigo); Trebisacce
(G. Meringolo, L. Donnangelo); Sicilia Avola (G. Canonico);
Catania Osp. Cannizzaro (R. Coco, M. Franco); Messina Osp.
Papardo (A. Coglitore, A. Donato); Messina Osp. Piemonte (G. Di
Tano); Messina Policlinico (D. Cento, C. De Gregorio); Palermo
Casa Del Sole (M. Mongiovı̀); Palermo Osp. Buccheri La Ferla
FBF (A. M. Schillaci); Palermo Osp. Civico (U. Mirto); Palermo
Osp. Ingrassia (F. Clemenza); Palermo Villa Sofia (F. Ingrillı̀);
Piazza Armerina (A. Cavallaro, B. Aloisi); Trapani (G. Ledda, C.
Rizzo); Sardegna Cagliari Brotzu (M. Porcu, S. Salis, L. Pistis);
Cagliari Osp. SS. Trinità (G. Pili, S. Piras); Nuoro (I. Maoddi);
Sassari (F. Uras).