Download Long-term mortality predictors in patients with chronic bifascicular

CLINICAL RESEARCH
Europace (2009) 11, 1201–1207
doi:10.1093/europace/eup181
Electrophysiology and Ablation
Long-term mortality predictors in patients
with chronic bifascicular block
Julio Marti-Almor*, Merce Cladellas, Victor Bazan, Carmen Altaba,
Miguel Guijo, Joaquim Delclos, and Jordi Bruguera-Cortada
Cardiology Department, Hospital del Mar, 25-29 Passeig Maritim, Barcelona 08003, Spain
Received 15 April 2009; accepted after revision 10 June 2009; online publish-ahead-of-print 3 July 2009
To evaluate the long-term mortality rate and to determine independent mortality risk factors in patients with bifascicular block (BFB). Patients with BFB are known to have a higher mortality risk than the general population, not only
related to progression to atrio-ventricular block but also due to the presence of malignant ventricular arrhythmias.
Previous observational and epidemiological studies including a high proportion of patients with structural heart
disease have shown an important cardiac mortality rate and may not reflect the real outcome of patients with BFB.
.....................................................................................................................................................................................
Methods
From March 1998 until December 2006, we prospectively studied 259 consecutive BFB patients, 213 (82%) of whom
and results
presenting with syncope/pre-syncope, undergoing electrophysiological study. After a median follow-up of 4.5 years
(P25:2.16– P75:6.41), 53 patients (20.1%) died, 19 (7%) of whom due to cardiac aetiology. Independent total mortality
predictors were age [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01–1.09], NYHA class II (HR 2.17, 95%
CI 1.05 –4.5), atrial fibrillation (HR 2.96, 95% CI 1.1 –7.92), and renal dysfunction (HR 4.26, 95% CI 2.04–9.01). An
NYHA class of II (HR 5.45, 95% CI 2.01–14.82) and renal failure (HR 3.82, 95% CI 1.21–12.06) were independent
predictors of cardiac mortality. No independent predictors of arrhythmic death were found.
.....................................................................................................................................................................................
Conclusion
Total mortality, especially of cardiac cause, is lower than previously described in BFB patients. Advanced NYHA class
and renal failure are predictors of cardiac mortality.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Mortality † Bifascicular block † Electrophysiological study
Introduction
Chronic bifascicular block (BFB) defined as left bundle branch
block (LBBB) or right bundle branch block (RBBB) associated
either with a left anterior fascicular block (LAFB) or left posterior
fascicular block (LPFB) is a particular form of intraventricular conduction delay. The estimated prevalence in an adult non-selected
population is 1–1.5%,1 and the mortality rate ranges 2–14%.2
This mortality rate is higher than in an age- and sex-matched population without BFB in the Framingham study.3 However several epidemiological studies have shown a similar longevity for patients
with or without bundle branch block.4,5
However in observational studies, BFB patients with syncope,
especially in the setting of structural heart disease and low left ventricular ejection fraction (LVEF), showed a higher mortality rate,
ranging 29 –38%.2,6,7 In these patients, pacemaker implantation
prevents death for advanced atrio-ventricular block,8 but this
therapy does not improve survival and neither decreases the incidence of sudden cardiac death (SCD) that ranges 14–42%.7,9 – 11
These findings suggest that the poor long-term prognosis in BFB
patients may be partially related to an increased risk of malignant
ventricular arrhythmias in the setting of a severely impaired conduction system, especially in the presence of severe ventricular
dysfunction.
The discrepancy between epidemiological and observational
studies may be explained by a higher proportion of patients with
structural heart disease and low LVEF in those series reporting a
high cardiac mortality rate, including SCD,9,10,12 and also by the
fact that most of these studies were carried out in the 1980s,
when the treatment of structural heart disease was quite different
from that employed currently, and could not represent a majority
of patients with BFB nowadays.
* Corresponding author. Tel: þ34 932483489, Fax: þ34 932483489, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2009. For permissions please email: [email protected].
Downloaded from europace.oxfordjournals.org by guest on December 3, 2010
Aims
1202
The purpose of the present study is to describe the clinical
characteristics and outcome of a cohort of patients with BFB
undergoing an electrophysiological study (EPS), in order to ascertain the total, cardiac, and arrhythmic mortality rate and to identify
their independent risk factors in a long-term follow-up period.
Methods
Patient population
Electrophysiological study
The EPS was performed in the fasting and unsedated state, after withdrawal of all anti-arrhythmic medication for at least five or more
half-lives. Two tetrapolar 6 French catheters with a 5 mm interelectrode distance were inserted percutaneously under local anaesthesia
through the femoral vein and positioned in the high right atrium
(and subsequently moved to the right ventricular apex for ventricular
stimulation when considered necessary) and the His bundle region.
Our study protocol included assessment of the basal conduction intervals and refractory periods, as described elsewhere.8 Programmed ventricular stimulation was performed in all patients from the apex and the
outflow tract of the right ventricle with up to three extra stimuli;
minimal coupling interval was 200 ms, and basic drive pacing was performed at cycle lengths of 600, 500, and 430 ms. The endpoint of ventricular stimulation was induction of monomorphic ventricular
tachycardia (VT) or sustained ventricular arrhythmia requiring electrical cardioversion. Stimuli were delivered at twice the diastolic
threshold with a pulse width of 2 ms using the universal programmable
stimulator (Biotronik Inc., Berlin, Germany). The intracardiac and
surface ECG (leads V1, V6, I, and III) were recorded on a laboratory
system duo (Bard Inc., Boston, USA), at a paper speed of 100 mm/s.
The EPS was considered positive for diagnostic of conduction disturbance when the HV interval was 70 ms in symptomatic patients or
100 ms in asymptomatic patients either at baseline or after pharmacological stress-testing with ajmaline (1 mg/kg) or procainamide
(10 mg/kg) and also if infra-Hisian block was detected during rapid
atrial pacing from 500 ms to the Wenckebach cycle length. The EPS
was also considered positive if sustained ventricular arrhythmias able
to reproduce clinical symptoms were induced.
Treatment and follow-up
Symptomatic patients with a positive result on the EPS were treated
with pacemaker or an implantable cardioverter defibrillator (ICD) as
appropriate, according to the guidelines of the European Society of
Cardiology.15 All patients were followed up at the outpatient’s clinic
3, 6, 12, and 24 months after EPS. Patients with a pacemaker were followed up at least once a year for life. Patients with an ICD were controlled at least every 6 months for life. In patients with a negative EPS, a
tilt test was performed according to the Italian protocol16 and/or a
loop recorder inserted to ascertain the cause of syncope. Asymptomatic patients were followed up once a year for 2 years and then
referred to the general practitioner. In March 2007, all patients
received a telephone call in order to check for life status, syncope
recurrences, and hospitalization for any reason. If the patient was
dead, the cause was investigated by the hospital records department
or by the General Mortality Registry of Catalonia, Spain.
Statistical analysis
Continuous data with a normal distribution are presented with mean
and standard deviation. Those with a not-normal distribution are
expressed as median with 25th and 75th percentile. Categorical data
are presented as percentages.
We analysed three separated models of mortality: total, cardiac, and
arrhythmic mortality. For each model, clinical characteristics, ECG, and
EPS results were compared by using Student’s t-test or ANOVA for
Gaussian variables and by the Mann– Whitney or Kruskal– Wallis
test for non-Gaussian variables. Differences in proportions were compared by a x2 analysis or Fisher’s exact test, as appropriate.
We assessed the relationship between clinical characteristics, ECG
disturbances, and EPS results for each of the three mortality outcomes,
by using a univariate Cox proportional hazards survival model. The
multivariate Cox model included all variables that achieved at least
marginal significance (P-value ,0.1) as predictors in each model of
mortality in the univariate analysis. Those variables for which their
exclusion did not change significantly the likelihood of the model
and did not change .15% the estimates of the remainder variables
were removed of the model. First-order interactions were also
Downloaded from europace.oxfordjournals.org by guest on December 3, 2010
Between March 1998 and December 2006, 284 consecutive patients
with chronic BFB underwent EPS and were prospectively included
and analysed. The LBBB and RBBB patterns were diagnosed according
to standard definition.13 Left anterior fascicular block was defined as a
mean frontal QRS axis less than 2308 and LPFB as a mean frontal QRS
axis .908 in the absence of ECG criteria for right ventricular
hypertrophy.
The study population was divided into patients with syncope/presyncope (‘symptomatic’ group) or other symptoms/no symptoms
(‘asymptomatic’ group). Syncope was defined as complete loss of consciousness with a loss of postural tone with spontaneous and quick
recovery. Pre-syncope was defined as a near-syncope situation but
without complete loss of consciousness. Patients with advanced congestive heart failure (NYHA class IV), candidates for resynchronization
therapy, those with life expectancy under 1 year, those who did not
give the informed consent, and those with unspecific conduction
delay disturbance not accomplishing ECG criteria for either LBBB or
RBBB were excluded. Additionally, patients with an incomplete clinical
follow-up were also excluded.
The study protocol was explained in detail to each patient before
inclusion, and signed informed consent was obtained.
Before EPS was performed, all patients were carefully interviewed,
with special emphasis on the presence/absence of dyslipaemia, hypertension, diabetes, smoking history, and previous or present cardiac
disease. Ischaemic cardiomyopathy was defined as a 70% stenosis
of one or more epicardial coronary vessels as documented by angiography in patients with impaired systolic function. These variables
were confirmed when the patient received treatment for each of
them and considered potential risk factors. Smoking was considered
a risk factor when a patient was an active smoker at inclusion. The
severity of congestive heart failure was assessed by the New York
Heart Association (NYHA) classification, and class II or III was considered a potential risk factor. Careful physical examination including
carotid sinus massage (in the symptomatic group), routine laboratory
tests, and a Doppler echocardiography to characterize structural
heart disease were also performed. Renal function was evaluated by
estimation of glomerular filtration rate (eGFR) using the Modification
on Diet on Renal Disease equation14 (http://nephron.org/cgi-bin/
MDRD_GFR/cgi). Renal failure was divided into mild failure (eGFR
40 – 59 mL/min/1.73 m2) and severe failure (eGFR ,40 mL/min/
1.73 m2). Under 35% LVEF assessed by echocardiography (Simpson’s
rule) was defined as a potential risk factor. The QRS width and the
PR interval in the 12-lead ECG were also assessed.
J. Marti-Almor et al.
1203
Mortality predictors in chronic bifascicular block
tested. Results are expressed in hazard ratio (HR) and 95% confidence
interval (CI).
Kaplan– Meier survival curves with log-rank test evaluated univariate
associations between clinical events and each kind of mortality.
Results
Electrophysiological study
In 162 patients (63%), the EPS was positive either for the diagnosis
of conduction disturbances (158 patients) or for VT induction
(6 patients). Of note, VT inducibility was not associated with a
higher mortality of any kind (Table 2). An ICD was implanted in
seven patients: six inducible patients and one non-inducible
patient by fulfilling the MADIT II criteria. All inducible patients
had structural heart disease (ischaemic aetiology in five and
Table 1 Total mortality descriptive analysis
Variables
Total (n 5 259)
Alive (n 5 206)
Dead (n 5 53)
Male, n (%)
176 (68)
139 (67)
37 (69)
0.93
Age ( mean + SD)
Syncope/pre-syncope, n (%)
73 + 9
213 (82)
72 + 9
168 (82)
75 + 9
45 (83)
0.08
0.85
P-value
...............................................................................................................................................................................
NYHA .II, n (%)
60 (23)
39 (19)
21 (40)
0.002
Structural heart disease, n (%)
Hypertension, n (%)
122 (47)
172 (66)
87 (42)
134 (65)
35 (65)
38 (71)
0.004
0.46
Diabetes, n (%)
77 (30)
60 (29)
17 (32)
0.69
Dyslipaemia, n (%)
Active smoker, n (%)
77 (30)
29 (11)
64 (31)
24 (12)
13 (24)
5 (9)
0.35
0.79
LVEF,35%, n (%)
30 (12)
19 (9)
11 (20)
0.01
Renal function
eGFR 60 mL/min/1.73 m2
151 (58)
130 (63)
21 (40)
83 (32)
64 (31)
18 (34)
26 (10)
12 (6)
14 (26)
eGFR 40– 59 mL/min/1.73 m2
eGFR ,40 mL/min/1.73 m2
ECG
,0.001
Atrial fibrillation, n (%)
12 (5)
6 (3)
6 (11)
0.02
PR interval .200 ms, n (%)
QRS width, ms
128 (49)
144.6 + 15.1
101 (48)
143.9 + 14.6
27 (50)
146.1 + 17.0
0.84
0.36
LAFB þ RBBB, n (%)
LPFB þ RBBB, n (%)
131 (50)
22 (8)
101 (48)
19 (9)
30 (56)
3 (6)
LBBB, n (%)
106 (40)
86 (41)
20 (37)
0.53
158 (61)
121 (59)
37 (70)
0.36
6 (2)
4 (2)
2 (4)
0.61
Kind of BFB
EPS
HV interval .70 ms, n (%)
VT inducibility, n (%)
NYHA, New York Heart Association functional class; LVEF, left ventricular ejection fraction; BFB, bifascicular block; LBBB, left bundle branch block; RBBB, right bundle branch
block; LAFB, left anterior fascicular block; LPFB, left posterior fascicular block; eGFR, estimation of glomerular filtration rate; VT, ventricular tachycardia.
Downloaded from europace.oxfordjournals.org by guest on December 3, 2010
Twenty-five of the initial 284 patients were excluded from analysis
due to incomplete clinical information or unspecific ECG conduction delay. Of the remaining 259 patients, 213 (82%) were studied
for syncope or pre-syncope, and 46 patients were asymptomatic.
The symptomatic group included 172 patients with syncope and
41 with pre-syncope, without baseline clinical differences
between them. The asymptomatic group included 22 BFB patients
undergoing catheter ablation of supraventricular tachycardia and
an additional 24 patients with BFB undergoing EPS for preoperative risk evaluation, due to the presence of severe
conduction disturbances.
The clinical characteristics of the study population are shown in
Table 1. The predominant structural heart disease was ischaemic
and hypertensive cardiomyopathy (46 patients each), followed by
dilated cardiomyopathy (20), valvular heart disease (10), and
1 single case of obstructive hypertrophic cardiomyopathy.
Median LVEF of this subgroup was 53% (P25:39–P75:59).
The QRS duration in symptomatic patients was significantly
shorter [140 (131 –148) ms] as opposed to the asymptomatic
group [152 (148–168) ms; P ¼ 0.016]. Similarly, the PR interval
was 290 (220– 372) ms in the asymptomatic, as opposed to 215
(186 –249) ms in the symptomatic group (P ¼ 0.006).
In the whole group, the median LVEF was 63% (P25:54 –P75:66),
and in 30 patients (12%), it was ,35%. Sixty patients (23%) were
in NYHA class II or higher. Patients were under statins,
ACE-inhibitors, angiotensin receptor blockers, and beta-blockers
in 28, 41, 19, and 12%, respectively. There were no differences
in the beta-blockers intake between symptomatic (24/217) and
asymptomatic (8/46) patients.
1204
J. Marti-Almor et al.
Table 2 Hazard ratio for total and cardiac mortality during the follow-up using bivariate Cox models
Variables
Total mortality (n 5 53)
Cardiac mortality (n 5 19)
Male
1.03 (0.58–1.84)
1.04 (0.39– 2.74)
Age
Syncope/pre-syncope
1.04 (1.01–1.08)
1.08 (0.52–2.21)
1.0 (0.95–1.05)
1.86 (0.43– 8.05)
...............................................................................................................................................................................
NYHA .II
3.13 (1.79–5.51)
6.93 (2.69– 17.87)
Structural heart disease
Hypertension
2.3 (1.31– 4.04)
1.33 (0.74–2,39)
4.45 (1.47– 13.42)
2.94 (0.85– 10.13)
Diabetes
1.16 (0.64–2.08)
1.49 (0.58– 3.81)
Dyslipaemia
Active smoker
0.77 (0.41–1.47)
1.09 (0.64–1.87)
0.66 (0.22– 2.01)
1.06 (0.43– 2.62)
LVEF ,35%
2.95 (1.5– 5.78)
4.75 (1.77– 12.74)
Renal function
eGFR 60 mL/min/1.73 m2
Reference
eGFR 40–59 mL/min/1.73 m2
Atrial fibrillation
PR interval .200 ms
Kind of BFB
1.46 (0.78–2.75)
1.46 (0.49– 4.35)
5.06 (2.54–10.1)
5.82(1.93–17.52)
2.77 (1.18–6.51)
0.05 (indeterminate)
1.35 (0.75–2.42)
1.48 (0.59– 3.72)
LAFBþRBBB
Reference
LPFBþRBBB
LBBB
0.46 (0.14–1.53)
0.9 (0.51– 1.61)
0.46 (0.06– 3.6)
1.08 (0.42– 2.76)
0.95(0.53– 1.69)
2.07 (0.50–8.54)
1.06 (0.42– 2.71)
3.18 (0.42– 24.05)
EPS
HV interval .70 ms
VT inducibility
NYHA, New York Heart Association functional class; LVEF, left ventricular ejection fraction; BFB, bifascicular block; LBBB, left bundle branch block; RBBB, right bundle branch
block; LAFB, left anterior fascicular block; LPFB, left posterior fascicular block; eGFR, estimation of glomerular filtration rate; VT, ventricular tachycardia.
dilated cardiomyopathy in one) and LVEF ,35%. Six patients presented with appropriate shock ICD therapies during follow-up
(five inducible and one non-inducible). In 156 patients, a pacemaker was implanted, and in the follow-up, 102 patients used
the pacemaker for progression to atrio-ventricular block.
Total mortality
After a median follow-up period of 4.5 (P25:2.16–P75:6.41) years,
53 (20.1%) patients died. There were no differences between
syncope and pre-syncope patients. Cardiac aetiology was the
cause of death in 19 patients (7%). Of the 34 (13%) patients
with a non-cardiac death, 15 died from cancer and 19 due to a
concomitant illness such as pneumonia in 5, stroke in 4, cirrhosis
in 3, hip fracture in 3, sepsis of abdominal origin in 2, diabetic
cetoacidosis in 1, and aplastic anaemia in 1. The 2 year and
5 year cumulative survival rate was 94 and 79%, respectively
(Figure 1).
The analysis of clinical, electrocardiographic, and electrophysiological BFB patient characteristics identified the following predictors of total mortality (Table 1): An NYHA II (40% of deaths
vs. 19% of survivors; P ¼ 0.002), structural heart disease (65 vs.
42%, respectively; P ¼ 0.004), an ejection fraction ,35%
(20 vs. 9%, respectively; P ¼ 0.01), renal failure with an eGFR
Figure 1 Kaplan– Meier survival curves for total and cardiac
mortality. Total mortality was mainly due to non-cardiac aetiology. The 2 year total mortality rate was 6%.
,40 mL/min/1.73 m2 (26 vs. 6%, respectively; P , 0.001), and
atrial fibrillation (11 vs. 3%, respectively; P ¼ 0.02).
The total, cardiac, and arrhythmic mortality were not influenced
by the BFB type (Tables 1 and 2). Of note, an HV interval .70 ms
was not associated with an increased total mortality (Table 1). In
six patients, an HV interval 100 ms was observed at baseline,
Downloaded from europace.oxfordjournals.org by guest on December 3, 2010
eGFR ,40 mL/min/1.73 m2
ECG
1205
Mortality predictors in chronic bifascicular block
Table 3 Hazard ratio for total and cardiac mortality
and for the presence of ventricular arrhythmias during
the follow-up using multivariate Cox models
Variable
HR
95% IC
P-value
................................................................................
Total mortality
Age
1.04
1.01–1.09
0.02
Atrial fibrillation
eGFR ,40 mL/min/1.73 m2
2.96
4.29
1.10–7.92
2.04–9.01
0.03
,0.001
NYHA II
2.17
1.05–4.52
0.03
2.41
0.99–5.84
0.05
NYHA II
5.45
2.01–14.82
0.001
eGFR ,40 mL/min/1.73 m2
3.82
1.21–12.06
0.02
LVEF ,35%
Cardiac mortality
and in six additional patients, the administration of
infra-His-stressing drugs induced an HV interval 100 ms. No
differences in mortality were observed in this subset of patients.
Bivariate Cox regression analysis confirmed that the variables
implicated in the total mortality were atrial fibrillation, eGFR
,40 mL/min/1.73m2, NYHA II, structural heart disease, ejection
fraction ,35%, and age (Table 2).
The aforementioned univariate associations were tested in the
multivariate Cox model. This model showed that age, NYHA
II, atrial fibrillation, and eGFR ,40 mL/min/1.73 m2 were independent predictive factors for total mortality. Nevertheless,
LVEF ,35% was marginally significant (Table 3).
Cardiac mortality
In our series, 19 (7%) patients died from cardiac causes, 6 of whom
due to SCD, 11 from heart failure progression, and 2 from fatal
myocardial infarction. The descriptive analysis showed that the
variables related to cardiac mortality were the following: an
NYHA II (58% of cardiac deaths when compared with 21% in
the survivors, P , 0.001), structural heart disease (79 vs. 45%,
respectively; P ¼ 0.004), LVEF ,35% (33 vs. 10%, respectively;
P ¼ 0.01), and renal failure with eGFR ,40 mL/min/1.73 m2 (42
vs. 15%, respectively; P ¼ 0.02). Hypertension showed only marginal statistical significance.
In the bivariate Cox regression analysis, the variables that
showed an increased risk for cardiac mortality were an NYHA
II (P 0.001), an LVEF ,35% (P ¼ 0.007), structural heart
disease (P ¼ 0.01), and eGFR ,40 mL/min/1.73 m2 (P ¼ 0.01), as
shown in Table 2. Multivariate Cox regression analysis demonstrated that only advanced NYHA class and depressed eGFR
increased the risk for cardiac mortality (Table 3).
Arrhythmic mortality
Six patients (2.3%) died from SCD. In only two of them, ventricular
fibrillation was the first rhythm detected by an emergency care
unit. The rest were possibly due to arrhythmic origin but
Discussion
The main finding in our study is a lower total mortality rate (20.1%
in a median follow-up of 4.5 years) than expected in comparison
with previous studies, mainly due to lower cardiac and sudden
death mortality rates in our BFB population. Dhingra et al.17
analysed 517 patients with BFB, and a total mortality of 38% was
determined after a 7 year follow-up period, with SCD being
mainly responsible for this mortality rate. In addition, McAnulty
et al.7 established a total mortality rate among BFB patients of
29%, 42% of which due to SCD. These discrepancies could be
related to a higher percentage of patients with structural heart
disease and lower LVEF in these previous studies. Moreover,
drugs such as ACE-inhibitors, angiotensin receptor blockers, betablockers, or statins, with proven survival benefits, were less
frequently administered when these studies were published than
currently. Finally, whether a higher proportion of BFB patients
undergoing pacemaker implantation in our population may have
lowered the mortality rate is not clear.
In more recent studies, Tabrizi et al.11 analysed 100 patients with
BFB, reporting a mortality rate of 33%, half of them due to SCD. In
this study, 57% of patients had structural heart disease, with a
mean LVEF of 46%, and in 23% of them, the LVEF was ,35%. In
contrast, in our study, only 47% of patients had structural heart
disease, with median LVEF of 63% and only 12% of patients with
a severe left ventricular dysfunction (LVEF ,35%). Furthermore,
in Tabrizi et al.’s study, the proportion of patients treated with
ACE-inhibitors (27%) was much lower than in our study (41%),
with a similar rate of beta-blockers intake.
Importantly, the outcomes of our patient population are in
agreement with the B4-Study (Bradyarrhythmia Bundle Branch
Block Study).18 In this study of more than 400 patients with
chronic BFB (mainly LBBB), a similar total mortality rate of 5.7%
is described in a 18-month follow-up period (2 year total mortality
rate of 6% in our series). The clinical characteristics of the
B4-Study population, including a mean LVEF of 56 + 12% and
50% of structural heart disease, were similar to our study
(median of LVEF of 63% and structural heart disease present in
47% patients). We believe our study accurately represents the
current characteristics and clinical outcomes of patients with
BFB, especially those who are symptomatic for syncope or
pre-syncope.
Predictors of mortality in bifascicular
block patients
In the present study, an advanced NYHA functional class is associated with any kind of mortality. There is considerable evidence
supporting that patients with heart failure have a higher mortality
rate when conduction delay disorders are present. In the MADIT
II trial, which included more than half of patients with NYHA
II, a higher total and cardiac mortality rates were observed in
patients with intraventricular conduction delay, when compared
with patients with narrow QRS.19 Additional studies have
Downloaded from europace.oxfordjournals.org by guest on December 3, 2010
eGFR, estimation of glomerular filtration rate; NYHA, New York Heart
Association functional class; LVEF, left ventricular ejection fraction.
unwitnessed. No independent predictor for this kind of mortality
was found.
1206
Study limitations
In this analysis, a comparative age- and sex-matched group of
patients without BFB was not used. Nevertheless, the mortality
rate in our study is lower than previously described and is essentially related to non-cardiac death. We believe that the use of a
comparative group would have not changed our results. A relatively short-term follow-up in our series may also account for
the low mortality rate observed. However, previous series with
even shorter follow-up periods have shown higher mortality
rates than in the present study. It is unclear whether a larger
number of patients would have influenced the mortality results
in our series. The small number of patients with unspecific EGC
conduction delay (only four patients) did not allow us to establish
the long-term outcome of this subset of patients. Bifascicular block
patients with low ejection fraction and structural heart disease may
not be sufficiently represented in our study and might have
changed the results obtained.
We included 24 asymptomatic patients for surgery risk evaluation, and this subgroup, although asymptomatic, had a more
extensive conduction disorder. However, we believe that this
selection bias has not affected the final results of the study.
Conclusions
In this study, the total and especially cardiac mortality rates are
lower than previously reported. A different drug strategy including
ACE-inhibitors, angiotensin receptor blockers, beta blockers, or
statins, and the fact of including a relatively healthy population
may have changed the natural history of patients with chronic
BFB. An advanced NYHA class and the presence of renal failure
are independent predictors of total and cardiac mortality in
patients with chronic BFB.
Conflict of interest: none declared.
References
1. Scheinman MM, Peters RW, Morady F, Sauve MJ, Malone P, Modin G. Electrophysiologic studies in patients with bundle branch block. Pacing Clin Electrophysiol
1983;6:1157 –65.
2. McAnulty JH, Kauffman S, Murphy E, Kassebaum DG, Rahimtoola SH. Survival in
patients with intraventricular conduction defects. Arch Intern Med 1978;138:30 –5.
3. Schneider JF, Thomas HE Jr, Sorlie P, Kreger BE, McNamara PM, Kannel WB.
Comparative features of newly acquired left and right bundle branch block in
the general population: the Framingham study. Am J Cardiol 1981;47:931 –40.
4. Fahy GJ, Pinski SL, Miller DP, McCabe N, Pye C, Walsh MJ et al. Natural history of
isolated bundle branch block. Am J Cardiol 1996;77:1185 –90.
5. Smith S, Hayes WL. The prognosis of complete left bundle branch block. Am
Heart J 1965;70:157 –9.
6. Dhingra RC, Denes P, Wu D, Chuquimia R, Amat-y-Leon F, Wyndham C et al.
Syncope in patients with chronic bifascicular block. Significance, causative mechanisms, and clinical implications. Ann Intern Med 1974;81:302 –6.
7. McAnulty JH, Rahimtoola SH, Murphy E, DeMots H, Ritzmann L, Kanarek PE et al.
Natural history of ‘high-risk’ bundle-branch block: final report of a prospective
study. N Engl J Med 1982;307:137 –43.
8. Scheinman MM, Peters RW, Suave MJ, Desai J, Abbott JA, Cogan J et al. Value of
the H-Q interval in patients with bundle branch block and the role of prophylactic
permanent pacing. Am J Cardiol 1982;50:1316 –22.
9. McAnulty JH, Rahimtoola SH, Murphy ES, Kauffman S, Ritzmann LW, Kanarek P
et al. A prospective study of sudden death in ‘high-risk’ bundle-branch block.
N Engl J Med 1978;299:209–15.
10. Denes P, Dhingra RC, Wu D, Wyndham CR, Amat-y-Leon F, Rosen KM. Sudden
death in patients with chronic bifascicular block. Arch Intern Med 1977;137:
1005 –10.
11. Tabrizi F, Rosenqvist M, Bergfeldt L, Englund A. Long-term prognosis in patients
with bifascicular block—the predictive value of noninvasive and invasive assessment. J Intern Med 2006;260:31 –8.
Downloaded from europace.oxfordjournals.org by guest on December 3, 2010
underlined that heart failure patients with intraventricular conduction delay and/or QRS widening have an increased mortality
rate.20,21
In our study, the documentation of atrial fibrillation was associated with a higher total mortality rate. These results are in accordance with previous evidence of a higher mortality rate in patients
with atrial fibrillation, not exclusively due to a higher number of
stroke events.22 Surprisingly, in our series, atrial fibrillation
increases the total mortality but not the cardiac mortality.
Whether this incongruence accounts for the low number of
atrial fibrillation patients in our population is not clear.
It is generally accepted that an LVEF ,35% is clearly linked to a
higher mortality rate associated with SCD or progression of heart
failure.20 In our study, the survival rate of patients with low LVEF
after a 5 year follow-up was 50% in comparison with 84% in
patients with LVEF .35%, with a cardiac mortality rate of 33
and 10%, respectively, P ¼ 0.01. However, in the multivariate
Cox regression analysis for total mortality, LVEF ,35% was not
statistically significant (HR 2.4, 95% CI 0.99–5.8). This result can
be explained by the low proportion of patients with depressed
LVEF in our study.
More than half of cardiac deaths in our population were due to
heart failure. In this group (10 patients), the LVEF was not inferior
to the LVEF of patients who died from other cardiac causes (41 vs.
44%, respectively). Noteworthy, seven of these patients had
advanced atrio-ventricular block in the follow-up. Evolution to
terminal heart failure could have been facilitated by permanent
right ventricular apex stimulation in this subgroup, as supported
by previous evidence in BFB patients.21,23,24
According to previous studies,25,26 renal failure increases total
mortality and cardiac mortality in patients with BFB (39 vs. 11%
of total mortality; P , 0.001, and 42 vs. 15% of cardiac mortality;
P ¼ 0.02, compared with normal renal function patients,
respectively).
Induction of sustained monomorphic VT in the EPS is lower than
in previous studies in patients with BBF and syncope,27,28 probably
due to a relatively healthy population included in our study. Clinical
arrhythmic events during follow-up may not be predicted by inducibility either in symptomatic or in asymptomatic patients.29 In fact,
we were not able to demonstrate a relationship between VT inducibility and arrhythmic mortality, in accordance with previous evidence.30 In the MADIT II trial, among the 593 patients who
underwent EPS, no statistical differences in appropriate therapies
between inducible and non-inducible patients were found.31
Importantly, the absence of VT inducibility in our population was
associated with an excellent outcome, with no ventricular arrhythmia documentation during follow-up, except for a single patient.
It is suggested by this study that a strict control of the renal function, atrial fibrillation, and NYHA class might have an influence in
the prevention of total mortality in patients with BFB. In BFB
patients, an EPS may be indicated for the assessment of progression to advanced AV block, but not for mortality prediction,
especially in the setting of relatively healthy patients.
J. Marti-Almor et al.
Mortality predictors in chronic bifascicular block
23. Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R et al. Ventricular
pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 2002;
346:1854 –62.
24. Sweeney MO, Hellkamp AS, Lee KL, Lamas GA. Association of prolonged QRS
duration with death in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 2005;111:2418 –23.
25. Chonchol M, Goldenberg I, Moss AJ, McNitt S, Cheung AK. Risk factors for
sudden cardiac death in patients with chronic renal insufficiency and left ventricular dysfunction. Am J Nephrol 2007;27:7 –14.
26. Goldenberg I, Moss AJ, McNitt S, Zareba W, Andrews ML, Hall WJ et al. Relations
among renal function, risk of sudden cardiac death, and benefit of the implanted
cardiac defibrillator in patients with ischemic left ventricular dysfunction. Am J
Cardiol 2006;98:485 –90.
27. Click RL, Gersh BJ, Sugrue DD, Holmes DR Jr, Wood DL, Osborn MJ et al. Role
of invasive electrophysiologic testing in patients with symptomatic bundle branch
block. Am J Cardiol 1987;59:817 –23.
28. Ezri M, Lerman BB, Marchlinski FE, Buxton AE, Josephson ME. Electrophysiologic
evaluation of syncope in patients with bifascicular block. Am Heart J 1983;106:
693 –7.
29. Englund A, Bergfeldt L, Rehnqvist N, Astrom H, Rosenqvist M. Diagnostic value of
programmed ventricular stimulation in patients with bifascicular block: a prospective study of patients with and without syncope. J Am Coll Cardiol 1995;26:
1508 –15.
30. Buxton AE, Lee KL, DiCarlo L, Gold MR, Greer GS, Prystowsky EN et al. Electrophysiologic testing to identify patients with coronary artery disease who are at
risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators.
N Engl J Med 2000;342:1937 –45.
31. Daubert JP, Zareba W, Hall WJ, Schuger C, Corsello A, Leon AR et al. Predictive
value of ventricular arrhythmia inducibility for subsequent ventricular tachycardia
or ventricular fibrillation in Multicenter Automatic Defibrillator Implantation Trial
(MADIT) II patients. J Am Coll Cardiol 2006;47:98–107.
Downloaded from europace.oxfordjournals.org by guest on December 3, 2010
12. Dhingra RC, Wyndham C, Bauernfeind R, Denes P, Wu D, Swiryn S et al. Significance of chronic bifascicular block without apparent organic heart disease. Circulation 1979;60:33 –9.
13. Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. Boston: Little,
Brown; 1973. p238 – 9.
14. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S et al. Using
standardized serum creatinine values in the modification of diet in renal disease
study equation for estimating glomerular filtration rate. Ann Intern Med 2006;
145:247 –54.
15. Brignole M, Alboni P, Benditt DG, Bergfeldt L, Blanc JJ, Thomsen PE et al. Guidelines on management (diagnosis and treatment) of syncope—update 2004. Executive Summary. Eur Heart J 2004;25:2054 – 72.
16. Bartoletti A, Alboni P, Ammirati F, Brignole M, Del Rosso A, Foglia Manzillo G
et al. ‘The Italian Protocol’: a simplified head-up tilt testing potentiated with oral
nitroglycerin to assess patients with unexplained syncope. Europace 2000;2:339–42.
17. Dhingra RC, Palileo E, Strasberg B, Swiryn S, Bauernfeind RA, Wyndham CR et al.
Significance of the HV interval in 517 patients with chronic bifascicular block. Circulation 1981;64:1265 –71.
18. Moya A, Garcia-Civera R, Brugada J, Croci F, Menozzi C, Ammirati F et al. The
management of syncope in patients with bundle branch block: a multicenter prospective study. Europace 2008;10 (Suppl. 10):i 44.
19. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS et al. Prophylactic
implantation of a defibrillator in patients with myocardial infarction and reduced
ejection fraction. N Engl J Med 2002;346:877–83.
20. Rosanio S, Schwarz ER, Vitarelli A, Zarraga IG, Kunapuli S, Ware DL et al. Sudden
death prophylaxis in heart failure. Int J Cardiol 2007;119:291 – 6.
21. Sharma AD, Rizo-Patron C, Hallstrom AP, O’Neill GP, Rothbart S, Martins JB et al.
Percent right ventricular pacing predicts outcomes in the DAVID trial. Heart
Rhythm 2005;2:830 – 4.
22. Friberg L, Hammar N, Pettersson H, Rosenqvist M. Increased mortality in
paroxysmal atrial fibrillation: report from the Stockholm Cohort-Study of Atrial
Fibrillation (SCAF). Eur Heart J 2007;28:2346 –53.
1207