Download Left bundle-branch block is associated with increased 1

Left bundle-branch block is associated with
increased 1-year sudden and total mortality rate in
5517 outpatients with congestive heart failure: A
report from the Italian Network on Congestive
Heart Failure
Samuele Baldasseroni, MD,a,e Cristina Opasich, MD,b Marco Gorini, MS,a Donata Lucci, MS,a
Niccolò Marchionni, MD,c Maurizio Marini, MD,a,c Carlo Campana, MD,a Giampaolo Perini, MD,a
Antonella Deorsola, MD,a Giulio Masotti, MD,c Luigi Tavazzi, MD,d and Aldo P. Maggioni, MD,a on behalf of the
Italian Network on Congestive Heart Failure Investigators Florence and Pavia, Italy
Background A deleterious effect of complete left bundle-branch block (LBBB) on left ventricular function has been established. Nevertheless, the independent effect of a widened QRS on mortality rate in congestive heart failure (CHF) is still controversial. Therefore, we carried out this analysis to determine whether LBBB is an independent predictor of mortality in CHF.
Methods and Results We analyzed the large Italian Network on CHF Registry of unselected outpatients with
CHF of different causes. The registry was established by the Italian Association of Hospital Cardiologists in 1995. Complete
1-year follow-up data were available for 5517 patients. The main underlying cardiac diagnosis was ischemic heart disease
in 2512 patients (45.6%), dilated cardiomyopathy in 1988 patients (36.0%), and hypertensive heart disease in 714
patients (12.9%). Other causes were recorded in the remaining 303 cases (5.5%). LBBB was present in 1391 patients
(25.2%) and was associated with an increased 1-year mortality rate from any cause (hazard ratio, 1.70; 95% confidence
interval, 1.41 to 2.05) and sudden death (hazard ratio, 1.58; 95% confidence interval, 1.21 to 2.06). Multivariate analysis
showed that such an increased risk was still significant after adjusting for age, underlying cardiac disease, indicators of CHF
severity, and prescription of angiotensin-converting enzyme inhibitors and β-blockers.
Conclusion LBBB is an unfavorable prognostic marker in patients with CHF. The negative effect is independent of age,
CHF severity, and drug prescriptions. These data may support the rationale of randomized trials to verify the effects on mortality rate of ventricular resynchronization with multisite cardiac pacing in patients with CHF and LBBB. (Am Heart J
2002;143:398-405.)
Although the mortality rate from heart disease is
declining as a consequence of improved treatment and
primary prevention in industrialized countries,1 the
number of patients affected by congestive heart failure
(CHF) is still increasing. This is a consequence of
From the aItalian Association of Hospital Cardiologists Research Center, Florence,
the bDepartment of Cardiology, Salvatore Maugeri Foundation, Pavia, the cDepartment of Critical Care Medicine and Surgery, Section of Gerontology and Geriatric
Medicine, University of Florence, the dDepartment of Cardiology, San Matteo Hospital, Pavia, and the eDepartment of Internal Medicine and Cardiology, University
of Florence, Italy.
The Italian Network on Congestive Heart Failure Registry was supported in part by
Merck Sharp & Dohme spa Italy.
See the Appendix for a complete list of participating Centers and Investigators.
Submitted May 16, 2001; accepted October 25, 2001.
Reprint requests: Aldo P. Maggioni, MD, ANMCO Research Center — Via La
Marmora 34, 50121 Florence, Italy.
E-mail: [email protected]
Copyright 2002, Mosby, Inc. All rights reserved.
0002-8703/2002/$35.00 + 0 4/1/121264
doi:10.1067/mhj.2002.121264
increased longevity and of the age-associated increase in
the prevalence of heart diseases in general, and of CHF
in particular.2 The number of patients with CHF has
increased dramatically in all age groups and by almost
500% in the more than 85 year age group from 1950 to
1993.1 Projections suggest that by the year 2016 the
absolute number of patients with CHF will further
increase from 1996 by 55.9% and 52.5% in the 65 to 75
year and the more than 75 year age groups, respectively.1
Among the many clinical and pathophysiologic factors
that have been proposed as prognostic indicators in
CHF, reduced left ventricular ejection fraction,3,4 neurohormonal activation,3 and reduced exercise tolerance
expressed as peak oxygen consumption,3,5,6 or performance in the 6-minute walk test,7 have been identified as
independent predictors of mortality rate. Data concerning the prognostic significance of intraventricular conduction defects and, in particular, of complete left bun-
American Heart Journal
Volume 143, Number 3
dle-branch block (LBBB) in CHF are more conflicting.
In fact, the deleterious effect of LBBB on left ventricular
systolic and diastolic function has been established in
subjects without overt heart disease8 and in patients
with dilated cardiomyopathy,9 and whether mortality
rate is increased independently with a widening of QRS
is still controversial.10-18
Therefore, we carried out this analysis of a database
of unselected outpatients with CHF of different
causes, who were followed by a large number of cardiologic centers in Italy. The purpose was evaluation
of the prevalence of complete LBBB and testing of
whether complete LBBB is an independent predictor
of all-cause mortality and of sudden death in patients
with CHF.
Methods
Study design, collected data, and definitions
Data for this analysis were originated from the database of
the Italian Network CHF Registry,19 a survey designed in 1995
by an ad hoc committee of the Italian Association of Hospital
Cardiologists (Florence, Italy). One-hundred fifty cardiologic
centers accepted participation in the study. Centers were distributed across the national territory and were more frequently located in Northern (46%) than in Central (24%) or
Southern (30%) Italy, well representing the whole country.
Short training sessions were organized to prepare clinicians to
collect and enter data with standardized methods. With an ad
hoc designed software, patient data were recorded at each
center by trained cardiologists and then were pooled into a
single database at the Italian Association of Hospital Cardiologists Research Center. Entry into the database required that
the patient had a diagnosis of New York Heart Association
(NYHA) classification I to IV CHF on the basis of the guidelines of the European Society of Cardiology.20 Demographic,
clinical, instrumental, and laboratory variables and information on drug therapy were collected for each patient. At baseline, a 12-lead electrocardiogram was recorded and coded by a
single cardiologist at each participating center, with a standardized format outlined in the database. In particular, presence of LBBB was recorded and QRS duration was coded as
less than 120 ms, 120 to 140 ms, or more than 140 ms. This
information was used by the computer program to control for
the acceptability of the diagnosis of LBBB and to distinguish
between incomplete (QRS duration, 120 to 140 ms) and complete (QRS duration, >140 ms) block. Patients were followed
according to the routine clinical practice of the participating
centers. In this context, patients underwent standard chest xray, 24-hour Holter electrocardiogram monitoring, 2-dimensional echocardiography, and blood sampling for the most
common laboratory tests (eg, creatinine level, electrolyte
level, etc) when the attending cardiologists deemed them necessary. Cardiologists at the participating centers were responsible for defining the cause of CHF and the NYHA classification, noting whether a 3rd heart sound was audible and
computing the cardiothoracic ratio. When an echocardiographic examination was performed, calculation of left ventricular ejection fraction from 4-chamber apical echocardiographic view was also done. Ventricular tachycardia was
Baldasseroni et al 399
defined as an episode of tachycardia with widened QRS that
lasted longer than 3 beats with a heart rate of more than 100
beats/min, as revealed with 24-hour Holter electrocardiogram
monitoring. Renal dysfunction was diagnosed for serum creatinine level of more than 2.5 mg/dL. Previous hospitalizations
for CHF in the last year were also recorded. After the baseline
visit, the patients were followed. In the case of out-of-hospital
death, the event was confirmed with telephone interview of
patient’s relatives, with a standard questionnaire aimed at
determining the mode of death (sudden versus non sudden).
Study population
As of January 2000, 6593 patients had complete 1-year follow-up information. We excluded from this analysis 1076
patients for any of the following reasons: CHF as the result of
primary valvular heart disease (n = 745), inadequate quality of
electrocardiogram (n = 270), and cardiac transplantation
within the 1st year of follow-up examination (n = 61). Thus,
the study population for this analysis consisted of 5517
patients.
Statistical analysis
The data were analyzed with the SAS statistical package and
are presented as mean ± standard deviation. The univariate
association of complete LBBB with several demographic and
clinical characteristics and with 1-year mortality rate was analyzed with the χ2 test. Cox proportional hazards multivariate
models with calculation of the adjusted hazard ratio and 95%
confidence interval were used to identify the independent
determinants of all-cause mortality rate and of mortality rate as
the result of sudden death. A 2-tailed P value of less than .05
was considered statistically significant.
Results
The study population of 5517 patients had a mean
age of 63 ± 12 years (range, 14 to 96 years) and
included 1295 women (23.5%) and 1544 cases (28.0%)
that were classified in NYHA class III to IV. The 1076
patients with complete 1-year follow-up data who were
excluded from this analysis had a similar age (65 ± 12
years; range, 17 to 91 years) but a larger prevalence of
women (38.6%; P < .01) and of NYHA classification III
to IV (38.8%; P < .01).
Complete left bundle-branch block: prevalence and
associated clinical characteristics
Complete LBBB was diagnosed in 1391 of 5517
patients (25.2%), complete right bundle-branch block
was diagnosed in 336 of 5517 patients (6.1%), and
other forms of intraventricular delay were diagnosed in
339 of 5517 patients (6.1%). Demographic and clinical
characteristics of patients with LBBB are reported in
Table I. The prevalence of patients older than 70 years
was similar in the group with and without LBBB, and
female patients were significantly more represented in
the group with LBBB. Cause of CHF was different
between the 2 groups, with dilated cardiomyopathy
American Heart Journal
March 2002
400 Baldasseroni et al
Figure 1
Table I. Main demographic and clinical characteristics of
5517 patients with congestive heart failure and presence or
absence of associated complete left bundle-branch block
Complete LBBB
Variable
One-year mortality rate for all-cause death and sudden death
in study population of 5517 patients with congestive heart failure (gray bars) and in subgroups with complete left bundlebranch block (black bars) or without complete left bundlebranch block (white bars). Unadjusted hazard ratio (HR) is also
reported with 95% confidence interval.
and ischemic heart disease being the most common
diagnosis in patients with and without LBBB, respectively. Although previous hospitalizations for CHF during the last year had a similar prevalence in both
groups, there were several indicators of greater severity
of clinical status in patients with LBBB as compared
with those without LBBB. In particular, LBBB was associated with higher prevalence of NYHA classification III
to IV CHF, reduced systolic blood pressure, 3rd heart
sound, and abnormally increased cardiothoracic ratio
(>0.55), while the prevalence of a heart rate higher
than 100 beats/min was similar in the 2 groups.
Echocardiographic results were available and of adequate quality to permit a reliable measurement of left
ventricular ejection fraction in 3392 of 5517 patients
(61.5%), a proportion that was similar in patients with
and without LBBB (2523 of 4126 [61.1%] versus 869 of
1391 [62.5%]; P = not significant). Echocardiographic
results also indicated a greater disease severity in
patients with LBBB, who had a higher prevalence rate
of severely reduced left ventricular ejection fraction
(<30%). Conversely, the prevalence rate of chronic
atrial fibrillation was higher in the group without LBBB,
and ventricular tachycardia and renal failure did not differ between the 2 groups. Significantly higher proportions of patients with LBBB were undergoing treatment
with diuretics, angiotensin-converting enzyme (ACE)
inhibitors, digoxin, and amiodarone, while nitrates,
Age > 70 years
Female gender
CHF cause
Dilated cardiomyopathy
Ischemic heart disease
Hypertensive heart disease
Other causes
Previous hospitalization for CHF
NYHA classification III to IV
Heart rate ≥ 100 beats/min
Systolic blood pressure
<100 mm Hg
100 to 130 mm Hg
>130 mm Hg
3rd heart sound
CT ratio > 0.55
LVEF
<0.30
0.30 to 0.40
>0.40
Chronic AF
Ventricular tachycardia
Renal failure
Drug prescriptions
Diuretics
ACE inhibitors
Digoxin
Nitrates
Antiplatelet agents
Amiodarone
β-blockers
Ca-antagonists
Other antiarrhythmic agents
Present
Absent
P
(n = 1391) (n = 4126) value
30.0%
29.3%
31.7%
21.5%
NS
.001
49.3%
33.7%
12.7%
4.2%
56.4%
32.8%
10.9%
31.6%
49.5%
13.0%
5.9%
54.3%
26.4%
10.7%
3.9%
61.2%
34.9%
34.2%
63.2%
2.7%
54.2%
43.1%
22.2%
55.0%
49.2%
40.3%
10.5%
13.3%
28.5%
2.1%
30.4%
44.5%
25.1%
19.3%
28.8%
2.5%
.001
NS
NS
88.6%
87.4%
71.8%
38.7%
31.4%
24.7%
16.2%
9.7%
1.8%
82.0%
82.8%
62.8%
43.2%
38.5%
20.0%
19.0%
14.3%
2.2%
.001
.001
.001
.003
.001
.001
.017
.001
NS
.001
NS
.001
NS
.001
.001
.040
.001
LBBB, Left bundle-branch block; CHF, congestive heart failure; NYHA, New York
Heart Association; CT, cardiothoracic; LVEF, left ventricular ejection fraction; AF,
atrial fibrillation; ACE, angiotensin-converting enzyme; NS, not significant.
antiplatelet agents, β-blockers, and Ca-antagonists were
prescribed more frequently to patients without LBBB.
Left bundle-branch block and prognosis
Overall, 659 of 5517 patients (11.9%) died during the
1-year follow-up period, with 46.4% (n = 306) of deaths
being classified as sudden. The 1-year all-cause mortality rate for patients with LBBB was 16.1% (224 of
1391), for patients with right bundle-branch block was
11.9% (40 of 336), and for patients with other intraventricular abnormalities was 8.8% (30 of 339). All-cause
mortality and mortality rates as the result of sudden
death were significantly greater among patients with
LBBB (Fig 1). Adjusted analysis was performed to predict the adjusted hazard ratio for all-cause death and
American Heart Journal
Volume 143, Number 3
Baldasseroni et al 401
Table II. Independent predictors of 1-year risk of all-cause
death in 5517 patients with congestive heart failure
Variable
Age (years)*
Ischemic heart disease (yes vs no)
Previous hospitalization for CHF
(yes vs no)
NYHA (III to IV vs I to II)
Heart rate (beats/min)*
Systolic blood pressure (mm Hg)*
3rd heart sound (yes vs no)
Chronic AF (yes vs no)
Ventricular tachycardia (yes vs no)
Renal failure (yes vs no)
ACE inhibitors (yes vs no)
β-blockers (yes vs no)
LBBB (yes vs no)
HR
95% CI
P
value
1.023 1.015-1.031
1.247 1.054-1.474
1.749 1.463-2.092
.0001
.0100
.0001
1.931
1.008
0.986
1.421
1.316
1.758
1.664
0.821
0.747
1.360
.0001
.0019
.0001
.0001
.0046
.0005
.0260
.0464
.0244
.0004
1.639-2.276
1.003-1.013
0.982-0.990
1.203-1.678
1.088-1.590
1.278-2.419
1.063-2.604
0.676-0.997
0.579-0.963
1.148-1.610
*Introduced as continuous variables.
Variables that were not significant (P > .10): sex, cardiothoracic ratio, left ventricular
ejection fraction, and prescription of antiplatelet agents. HR, Hazard ratio; CI, confidence interval; CHF, congestive heart failure; NYHA, New York Heart Association;
AF, atrial fibrillation; ACE, angiotensin-converting enzyme; LBBB, left bundle-branch
block.
sudden death at 1 year. In these models, we entered
age, heart rate, and systolic blood pressure as continuous variables and all the other variables presented in
Table I, as dichotomous variables, with inclusion of
LBBB as a covariate. Of the variables pertaining to drug
prescription, we included only those referring to agents
with proven effects on mortality rate in randomized
clinical trials. Thus, only prescriptions of ACE
inhibitors,21,22 antiplatelet agents,23 and β-blockers24,25
were entered as further dichotomous covariates in
these models, whose results are summarized in Tables
II and III.
The risk of all-cause death at 1 year was significantly
increased with increasing age and in the presence of
ischemic heart disease, previous hospitalization for
CHF, and several indicators of greater disease severity
or comorbidity, such as NYHA classification III to IV,
increased heart rate or reduced systolic blood pressure,
3rd heart sound, chronic atrial fibrillation, sustained
ventricular tachycardia, and renal failure (Table II). Prescription of ACE inhibitors and β-blockers had significantly independent protective effects against the risk of
all-cause death, and sex, the cardiothoracic ratio, left
ventricular ejection fraction, and prescription of antiplatelet agents were not confirmed to be significant
predictors of that risk (Table II). After adjustment for all
these covariates, complete LBBB still maintained its
unfavorable prognostic effect and, on average, it was
estimated to increase the risk of all-cause death at 1
year by 36% (Table II). The same variables, with the further exclusion of heart rate, renal failure, and prescription of ACE inhibitors, were significantly associated
Table III. Independent predictors of 1-year risk of sudden
death in 5517 patients with congestive heart failure
Variable
Age (years)*
Ischemic heart disease (yes vs no)
Previous hospitalization for CHF
(yes vs no)
NYHA (III to IV vs I to II)
Systolic blood pressure (mm Hg)*
3rd heart sound (yes vs no)
Chronic AF (yes vs no)
Ventricular tachycardia (yes vs no)
β-blockers (yes vs no)
LBBB (yes vs no)
HR
95% CI
P
value
1.015 1.004-1.027 .0106
1.319 1.030-1.691 .0285
1.879 1.445-2.445 .0001
1.520
0.990
1.714
1.375
1.961
0.665
1.348
1.193-1.936
0.984-0.996
1.346-2.181
1.038-1.823
1.250-3.078
0.455-0.972
1.051-1.729
.0007
.0007
.0001
.0266
.0034
.0352
.0188
*Introduced as continuous variables.
Variables that were not significant (P > .10): sex, cardiothoracic ratio, left ventricular
ejection fraction, heart rate, renal failure, and prescription of angiotensin-converting
enzyme inhibitors and antiplatelet agents. HR, Hazard ratio; CI, confidence interval;
CHF, congestive heart failure; NYHA, New York Heart Association; AF, atrial fibrillation; LBBB, left bundle-branch block.
with the risk of sudden death at 1 year (Table III). Also
in this multivariate model, LBBB was independently
associated with the risk of sudden death, which was
increased by almost 35% in the presence of this intraventricular conduction defect.
Discussion
The association of a wide QRS with increased mortality rate in CHF has been repeatedly investigated, but
results have been conflicting. Although some studies
showed that a wide QRS has an independent, unfavorable prognostic significance and increases the mortality
rate of patients with CHF during periods of follow-up
examination extended to 5 years,11,12,14 other studies
adopting similar multivariate approaches did not confirm this finding.10,13,16 Such discrepancies may arise
from the variable cutoffs adopted to define the conduction defect, ranging from a mild widening of the QRS
complex above 120 ms12 to complete LBBB10,11,13,14,16
and from large differences in the covariates included in
multivariate analyses. A further cause of conflicting
results may be represented by the variable cause of
CHF in the different studies that, in most cases, included only patients with dilated cardiomyopathy,12-14,16
with only 2 studies including a few patients with ischemic heart disease.10,11 However, all these studies included limited numbers of patients, ranging from 6216 to
441,13 and only recently a preliminary report of a large
survey of 3654 patients confirmed a direct association of
QRS duration with 1-year mortality rate in CHF from
dilated cardiomyopathy.18
Thus, we decided to limit our analysis only to the
prognostic significance of complete LBBB, with a data-
402 Baldasseroni et al
base that was produced by an Italian epidemiologic survey of outpatients referred to cardiology centers for
evaluation and treatment of CHF. The registry was large
enough to warrant adequate numbers for analysis.19
Our results from 5517 patients showed that complete
LBBB develops in as many as 25% of patients with CHF
of any origin and is associated with a 70% increase in
the univariate risk of all-cause mortality rate at 1 year.
At univariate analysis, complete LBBB was also associated with a series of CHF-specific indicators of disease
severity, and the relevance of these findings was further
supported by the observation that drugs that are commonly used in the routine control of CHF symptoms
were prescribed more frequently to patients with LBBB
than to those without LBBB. Conversely, patients without LBBB more frequently underwent treatment with
antiischemic or antithrombotic agents, a finding consistent with the observation that ischemic heart disease
was the most frequent cause of CHF in this subgroup.
Such complex relationships needed to be accounted
for in multivariate models that included several clinical
variables together with drug prescriptions. In fact, ACE
inhibitors, which were more frequently prescribed to
patients with LBBB, are well shown to be able to
reduce mortality rate in CHF,21,22 and a similar result
also can be obtained with antiplatelet agents23 and βblockers,24,25 which were used more frequently in
patients without LBBB. In this perspective, the strength
of our results is increased by the observation that, even
after adjusting for a large number of covariates that
included the most relevant variables that describe CHF
severity and prescriptions of these pharmacologic
agents, LBBB retained its unfavorable, independent
prognostic value, consisting of a 36% adjusted increase
in all-cause mortality rate at 1 year. In the multivariate
model predicting the risk of sudden death, the presence of LBBB maintained a quantitatively similar effect,
with an increase in the risk of almost 35%. Consistent
with previous findings from large randomized, controlled trials, our observational data showed a protective effect of ACE inhibitors21,22 and β-blockers24,25
against all-cause death. Prescription of antiplatelet
agents was not associated with such a significant protective effect that, however, had been previously
proven only in a subanalysis of the Studies of Left Ventricular Dysfunction trial.23
In the largest of the previous studies that showed the
unfavorable prognostic significance of intraventricular
conduction defects in CHF, age, creatinine level, heart
rate, and left ventricular ejection fraction were the
other independent predictors of 1-year total mortality
rate,18 and in our study, left ventricular ejection fraction was not confirmed to be an independent predictor
of death after multivariate analysis. This difference
might derive from several other variables that we took
into account which might have overridden the variance
American Heart Journal
March 2002
attributable to left ventricular ejection fraction. Among
these we included NYHA classification, which, even
though in gross terms, may well reflect exercise capacity, which has been proven as an important prognostic
factor in CHF.3,5-7
Asynchrony of left ventricular contraction26 and
impairment in the systolic and diastolic left ventricular
function8,9 induced by complete LBBB have been
clearly proven. In 1990, Hochleitner et al27 showed
that optimizing the atrioventricular delay with dualchamber cardiac pacing can improve the hemodynamic
profile of patients with CHF. These results were not
confirmed by other authors,28 and, even more importantly, because only right ventricular pacing is
involved, this proposed strategy cannot be relevant to
treatment of LBBB, for which prognosis is actually
worse. Multisite stimulation with the purpose of restoring ventricular relaxation and contraction sequences to
as homogeneous as possible appears to be more
promising, particularly for patients with LBBB. Indeed,
in patients with CHF, multisite cardiac pacing can
increase the abnormally shortened left ventricular filling time while simultaneously decreasing the interventricular septal dyskinesia—thereby improving left ventricular contractility (dP/dt)—and mitral valve
regurgitation.29 Several studies have recently shown
that left29,30 and biventricular cardiac pacing31-33 of
patients with CHF and complete bundle-branch block
can improve exercise tolerance, clinical status, healthrelated quality of life, and neurohormonal profile and
can reduce the hospitalization rate. Uncertainties
remain regarding the role of QRS duration or QRS
shortening as predictors of the response34 and the population of patients more likely to receive a benefit from
resynchronization therapy.35 A recent review of the
available literature suggests that patients with QRS
duration of more than 150 ms associated with significant mitral regurgitation and P-R prolongation possibly
could receive the most relevant benefit from resynchronization strategies.30,35,36 However, it has not yet been
shown that this therapeutic approach can also improve
the survival rate of patients with CHF. Our results provide a support to warrant controlled studies, adequately powered to specifically investigate this
unsolved issue.
There are some limitations in our study that must be
acknowledged. Because of the original purpose of the
database that we used for this analysis, examination of
electrocardiogram and measurement of QRS duration
were not carried out in a single, core laboratory with
standardized, blinded methods and quality control techniques. For this reason, we decided to limit the analysis
only to the effect of a definite diagnosis of complete
LBBB that, beyond morphologic criteria, was further
confirmed with a QRS duration of more than 140 ms
and, most importantly, was made in any case by quali-
American Heart Journal
Volume 143, Number 3
fied cardiologists. Another limitation is represented by
the fact that patients with complete 1-year follow-up
data who were excluded from the analysis were more
frequently women and presented a higher prevalence
rate of NYHA classification III to IV CHF. However, this
difference reflects predominantly the higher frequency
of valvular heart disease among women,19 a cause of
CHF that was not included in this analysis because its
natural history and management are completely different from that of CHF as the result of ischemic heart disease or dilated cardiomyopathy. Another limitation,
common to all observational and randomized control
trials for CHF, was represented by the fact that cause of
CHF was diagnosed without requiring a systematic use
of coronary angiographic data determining a possible
underestimation of the rate of ischemic cause.37 However, the relative prevalence of dilated cardiomyopathy
and ischemic heart disease that we found in such a
large population was consistent with data from other
studies of patients with CHF in which coronary angiographic data were not systematically obtained.38 We
also did not make any attempt at simultaneous adjustment for significant comorbidities other than renal failure, a limitation that becomes particularly important if
we consider that CHF is becoming a sort of geriatric
epidemic1,2 and that older patients commonly have an
increased burden of concomitant diseases that may
affect their overall prognoses.35 In this sense, our registry of outpatients followed by cardiologists included a
CHF population with a mean age lower than that generally observed in surveys conducted by internal medicine physicians, general practitioners, or geriatricians.
Finally, the definition of sudden death was not standardized but, rather, was on the basis of the individual
judgment expressed by the responsible cardiologist at
each center. However, it must be pointed out that the
almost 50% prevalence rate of sudden death that we
observed in our study is in keeping with results from
previous studies of patients with CHF.39,40
In spite of these limitations, we believe that our
analysis provides important information to support the
view that complete LBBB is unequivocally associated
with greater disease severity and mortality in patients
with CHF. The cause-and-effect relationship of this association, and whether correction of left ventricular asynchrony caused by the intraventricular conduction
defect may reduce such an increased risk of mortality,
should be investigated with adequately powered and
properly designed studies.
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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);
American Heart Journal
March 2002
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); Forlì (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); 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’Euge-
American Heart Journal
Volume 143, Number 3
Baldasseroni et al 405
nio (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 Divi-
sione (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. Mongiovì); Palermo Osp Buccheri
La Ferla FBF (A.M. Schillaci); Palermo Osp Civico (U. Mirto);
Palermo Osp Ingrassia (F. Clemenza); Palermo Villa Sofia (F.
Ingrillì); 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).
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