Atrial
fibrillation complicating congestive heart failure: Electrophysiological
aspects and its deleterious effect on cardiac resynchronization therapy
Quick View
Credits: Osmar Antonio Centurión, MD, PhD, FACC.
Division of Electrophysiology and Arrhythmias. Cardiovascular Institute. Sanatorio Migone-Battilana. Asunción, Paraguay, Departamento de Cardiología. Primera Cátedra de Clínica Médica. Hospital de Clínicas. Universidad Nacional de Asunción.
Running title:Atrial fibrillation and cardiac resynchronization
therapy.
Address for correspondence:Prof. Dr. Osmar Antonio Centurión, MD, PhD, FACC. Associate Professor of Medicine. Asunción National University. Chief, Division of Electrophysiology and Arrhythmias. Cardiovascular
Institute, Sanatorio Migone-Battilana, Eligio Ayala 1293, Asunción, Paraguay.
More successful
recognition and treatment of cardiovascular risk factors and diseases continues
to decrease mortality and increase the proportion of elderly population.
Therefore, there are more people with increased risk of developing heart
failure and atrial fibrillation in the course of their lives. Atrial
fibrillation (AF) can complicate the course of congestive heart failure (HF)
leading to acute pulmonary edema. The prevalence of AF, in patients with heart
failure, increases with the severity of the disease, reaching up to 40% in
advanced cases. In these HF patients, AF is an independent predictor of
morbidity and mortality increasing the risk of death and hospitalization.
Despite the excellent results obtained with different drugs, the optimal
medical treatment can fail in the intention to improve symptoms and quality of
life of patients with severe HF. Thus, the necessity to use cardiac devices
emerges facing the failure of optimal medical treatment in order to achieve
hemodynamic improvement and correction of the physiopathological alterations. Cardiac
resynchronization therapy (CRT) can reduce the interventricular and
intraventricular mechanical dissynchrony in HF patients. It has been shown that
CRT increases the left ventricular filling time, decreases septal dissynchrony,
mitral regurgitation, and left ventricular volumes allowing a hemodynamic
improvement. However, the development of AF in this setting can avoid the
beneficial effects of CRT. Therefore, this manuscript will review the available
data on this topic, the electrophysiological aspects of AF, to determine what
can be done in the event of an AF complicating congestive HF in CRT patients.
Key words:
Atrial fibrillation. Congestive heart failure. Cardiac resynchronization
therapy. AV node radiofrequency ablation.
Patients with heart failure are at increased risk of developing atrial
fibrillation (AF), despite medical improvements made in recent years. AF can
complicate the course of heart failure (HF) leading to worsen of HF symptoms
and acute pulmonary edema [1-6]. There are
several changes that predispose aging patients to develop AF. There is an increasing
prevalence of left ventricular wall hypertrophy in aging population [7]. The resulting left ventricular diastolic dysfunction with
aging may increase the size of the left atrium through an increase in filling
pressures predisposing elderly patients to develop AF. There are also
additional changes in the atria which facilitate the development of AF. Some
investigators have observed that normal histological changes in the atrial
muscle occur with advancing age which may set the milieu for AF to develop in
elderly patients [8-14].
Despite the excellent results obtained with different drugs, the optimal
medical treatment can fail in the intention to improve symptoms and quality of
life of patients with severe HF. Thus, the necessity to use cardiac devices
emerges facing the failure of optimal medical treatment in order to achieve
hemodynamic improvement and correction of the physiopathological alterations.
Cardiac resynchronization therapy (CRT) can reduce the interventricular and
intraventricular mechanical dissynchrony in HF patients with left bundle branch
block. It has been shown that CRT increases the left ventricular filling time,
decreases septal dissynchrony, mitral regurgitation, and left ventricular
volumes allowing a hemodynamic improvement. However, AF can avoid these
beneficial effects of CRT through the loss of synchronization between fibrillating
atria and ventricular contraction, the irregularity of the ventricular rhythm
and the frequently rapid ventricular response rate [1-3]. Therefore, this manuscript will review the available data on
this topic, the electrophysiological aspects of AF, to determine what can be
done in the event of an AF complicating congestive HF in CRT patients.
The prevalence of AF, in patients with HF, increases
with the severity of the disease, reaching up to 40% in advanced cases. In
these HF patients, AF is an independent predictor of morbidity and mortality
increasing the risk of death and hospitalization in 76% [4-6]. More successful recognition and treatment of cardiovascular
risk factors and diseases continues to decrease mortality and increase the
proportion of elderly population. Therefore, there are more people with
increased risk of developing HF and AF in the course of their lives.
There are only few studies on the electrophysiological
aspects of AF in congestive HF patients. Despite the clinical implications of
AF in HF, the reasons for its high prevalence are not clearly understood. Atrial
enlargement is recognized to play an important role in the development of AF in
HF patients. However, the atrial electrophysiological characteristics that
predispose to AF in patients with chronic HF have been scantly determined.
Studies of atrial electrical remodeling, that is observed as a result of sustained
AF, have provided some insights into the changes in atrial electrophysiology
that maintain the arrhythmia [15, 16],
however, it does not explain the nature of the underlying substrate that leads
to AF in chronic HF. Animal studies of atrial electrical remodeling in chronic HF
have demonstrated discrete regions of slow conduction associated with the
development of interstitial fibrosis but without apparent change in atrial effective
refractory periods [17]. Sanders et al [18]
demonstrated by electrophysiological and electroanatomic mapping in patients
with congestive HF that they have significant atrial remodelling characterized
by anatomic and structural changes. These changes included atrial enlargement,
regions of low voltage, and scarring; abnormalities of conduction, including
widespread conduction slowing and anatomically determined conduction delay and
block. They also observed increased refractoriness; and sinus node dysfunction.
These abnormalities encountered in their study were associated with an
increased inducibility and sustainability of AF and may be responsible in part
for the increased incidence of atrial arrhythmias in patients with congestive HF
[18].
AF is a common arrhythmia, and its prevalence in
patients with HF increases with aging and the severity of the disease. The process of aging and its effect on the
histological appearance of the conduction system of the heart have been scantly
described. It was reported that AF in some aged patients was associated with
loss of muscle fibers in the sinoatrial node and its approaches without any
clear pathological cause [8], while others have shown
degenerative changes in the conduction system with age [19].
The increase in prevalence of AF in older persons has
been reported to be associated with degeneration of the atrial muscle in
pathological studies. It was demonstrated in well designed studies, that there
is clear evidence in the human atrial muscle of age-related electrical
uncoupling of the side-to-side connections between bundles, related to the
proliferation of extensive collagenous tissue septa in intracellular spaces [20, 21].
Electrophysiological aspects of atrial fibrillation: Structural and anatomic abnormalities of the atria were
observed in patients with congestive HF and a strong predisposition to develop
AF. There is interesting information regarding the electrophysiological and
electroanatomic remodeling of the atria in patients with chronic HF [18]. It was demonstrated that patients with chronic HF and no
prior atrial arrhythmias have significant atrial remodelling characterized by
anatomic and structural changes, abnormalities of conduction, including
widespread conduction slowing and anatomically determined conduction delay and
block [18]. Despite the fact that the HF patients had no
prior atrial arrhythmias in that study, the electrophysiological abnormalities
were associated with an increased inducibility and sustainability of AF [18]. Pathological studies of the atria in chronic HF have shown
that structural abnormalities such as interstitial fibrosis, cellular
hypertrophy, and degeneration are present [17, 22,
23]. Atrial fibrosis has been demonstrated in the atria of
patients with chronic HF due to prior myocardial infarction and also from those
with idiopathic chronic HF [23]. Atrial arrhythmias
themselves may result in structural changes [24]. The
substrate for AF in patients with chronic HF may be due to structural
abnormalities and conduction delay rather than changes in refractoriness as occurs
in remodelling due to rapid atrial rates.
The electrophysiological mechanism of AF is considered to be either a
spiral wave with a continuously changing activation wavefront pattern, random
multiple independent reentrant wavelets wandering in the atria around arcs of
refractory tissue, or accentuation of focal activity originating mainly from
the pulmonary veins, superior vena cava, ligament of Marshall, or other sites
of the atrium. On the other hand, experimental studies clearly suggest, that
overload in ionized calcium in the senescent human atrial myocardial cells may
play an important role in arrhythmogenesis [25, 26]. The atrial myocardial cells in the elderly appear to be
more susceptible to arrhythmias when calcium homeostasis is disturbed and especially
under certain conditions that enhance calcium loading. Strong evidence of
abnormalities of the conduction system in an apparently healthy elderly
population has been demonstrated. Prolongation of the PR interval, high
prevalence of atrioventricular nodal and His-Purkinje disease, and unexplained
sinus node abnormalities were consistently found in older apparently healthy
individuals [27-30]. Muscle loss with
advancing age was found to be accompanied by an increase in fibrous tissue in
both the sinoatrial node and the internodal tracts [9-11]. It was strongly suggested that muscle loss and increase of
fibrosis in the atria is a slow but continuous process starting around 60 years
of age [8]. It was shown that aging has a profound effect on
structural changes and electrophysiological properties of the atrium. Fractionated
and abnormally prolonged atrial endocardial electrograms were recorded during
sinus rhythm in aging patients with paroxysmal AF. These abnormal atrial
electrograms may reflect nonsynchronised, delayed local electrical activity through
a diseased atrial muscle, which predispose patients to develop AF [12, 31-33]. Indeed, aging
has a profound impact on the histological and thus, electrophysiological
changes in the human atrial myocardium which contribute to the higher
prevalence of AF in the elderly. With a computer model of atrial fibrillation,
Moe et al [34] showed that an atrial disease characterized
by short and non-homogeneous atrial refractory periods, associated to
intra-atrial conduction disturbances, is considered an important factor in the
appearance and maintenance of AF. Non-homogeneity of refractory periods of
contiguous cells causes a slower conduction velocity of the stimulus that
propagates through partially repolarized cells, allowing the genesis of unidirectional
blocks and the appearance of multiple reentries [34]. These
findings were later corroborated by other investigators [35, 36]. Clinical electrophysiology has identified several atrial
features that may lead to the appearance of AF, sometimes with conflicting
results. The atrial refractory period and the extent of its dispersion can be
determined through the use of programmed atrial stimulation. This method also
allows eliciting several abnormal responses of the atrial muscle, such as
repetitive atrial firing, fragmented atrial activity, and intra-atrial
conduction delay [37-39]. These abnormal
responses are considered to indicate the presence of atrial vulnerability and
have been found to be related to the initiation and maintenance of AF [40-42]. Therefore, shorter atrial effective
refractory periods, greater dispersion of atrial refractoriness, and atrial
conduction delays, are of electrophysiological significance in the genesis of
AF. The precise electrophysiological and patho-physiological bases for AF
initiation and maintenance have not been resolved yet. As newer and more sophisticated
technology become available, controversies about AF genesis have reemerged,
which tells us that there is still a lot to learn about this arrhythmia. New
advances may be relevant to the ultimate understanding of the mechanisms of AF
initiation by the interaction of the propagating wavefronts with anatomic or
functional obstacles in their paths.
Pharmacological
measures in atrial fibrillation: Considering the high prevalence of AF in
the elderly and its deleterious effect on HF patients, it is very important to
maintain sinus rhythm in these already compromised patients. It has been shown
by several studies that pharmacological agents are effective in the treatment
of AF complicating HF. The angiotensine converting enzyme (ACE) inhibitors
produce a decrease in atrial pressure and in left ventricular end diastolic
pressure in patients with HF [43]. Therefore, it is possible
that these agents could decrease the susceptibility to develop AF simply by
decreasing atrial pressure and atrial wall stress and consequently by
attenuation of atrial enlargement. However, a decrease in atrial fibrosis was
also demonstrated experimentally only with ACE inhibitors despite similar
decrease in atrial pressure obtained with hidralazine [43].
Among other potentially beneficial mechanisms of ACE inhibition, a direct
antiarrhythmic effect can not be excluded. Even in the absence of HF, it seems
that angiotensine II directly contributes to atrial electrical remodelling. The
shortening of the atrial refractoriness during rapid atrial pacing is more
pronounced in the presence of angiotensine II. However, this electrical change
was prevented with a previous treatment with candesartan or captopril [44]. There was a beneficial effect on AF recurrence with
irbesartan in patients with persistant AF who underwent electrical
cardioversion [45]. When the drug was administered 3 weeks
before cardioversion combined with amiodarone, there was a significant decrease
in recurrent episodes of AF. The greater benefit of blocking angiotensine II
type I receptors occurred during the first 2 months after electrical
cardioversion, suggesting an important role of irbesartan in atrial electrical
remodelling after cardioversion. It is very interesting to note that the ACE
inhibitor is apparently more effective in patients with lesser symptoms [46]. This is probably due to potentially reversible milder
structural changes in patients with lesser symptoms. Therefore, irbesartan
demonstrated an additional positive effect to amiodarone, which is a class III,
multichannel ion blocker that significantly prolongs the atrial effective
refractory period.
The safety and efficacy of amiodarone was tested in HF patients in the
CHF-STAT trial and SCD-HeFT trial [47, 48].
The first trial demonstrated the safety profile of amiodarone in HF patients,
with a trend to better survival in non-ischemic cardiomyopathy [47].
The latter trial also showed that amiodarone did not influence significantly
overall mortality, however, a subgroup analysis showed an increased mortality
in NYHA class III HF patients [48]. Amiodarone is a potent
atrial antifibrillatory agent, that together with sotalol, quinidine, and verapamil
[47-54] were individually found to
significantly maintain sinus rhythm compared to placebo, reduce the incidence
of the first AF recurrence, and significantly reduce the ventricular rate. However,
amiodarone was found to be more effective than sotalol in prolonging time to
the first recurrence after DC cardioversion in patients with persistent AF [47]. Although amiodarone was not directly compared to
dronedarone yet, relatively similar findings were observed with dronedarone in
maintaining sinus rhythm and in reducing ventricular rate during arrhythmia
recurrence [55]. Dronedarone, a benzofuran derivative with
electro-pharmacologic profile closely resembling that of amiodarone but without
its adverse effects is a new, promising class III drug for the treatment of AF [55]. The SAFE-T investigators have demonstrated that amiodarone
is superior to sotalol for maintaining sinus rhythm. However, both drugs have
similar efficacy in patients with ischemic heart disease [49].
These class III antiarrhythmic drugs seem to exert their beneficial
anti-fibrillatory action by active blocking of potassium channels in patients
with structural heart disease. Dofetilide and azimilide, newer class III
antiarrhythmic drugs, were also tested to convert atrial fibrillation and
maintain sinus rhythm [56-60]. Although
the anti-arrhythmic efficacy of azimilide was superior to placebo, it was
significantly inferior to sotalol in patients with persistent AF and structural
heart disease. This modest antiarrhythmic efficacy, in addition to, the high
rate of torsade des pointes and marked QTc prolongation, limit azimilide
utilization for the therapeutic management of AF [56]. Class IA and IC drugs may cause lethal ventricular arrhythmias, and especially the latter
drugs are generally precluded in ischemic and structural heart disease.
Wachtell et al [61] demostrated that losartan, an angiotensine
receptor blocker (ARB), reduced the incidence of new-onset AF in 33% compared
to atenolol despite a similar blood pressure control in both treated groups. In
addition, the clinical relevance of preventing new onset AF was clearly
demonstrated, since AF was associated with a 2 to 5 fold greater cardiovascular
morbidity and mortality, cerebrovascular accidents and hospitalization due to
HF. New onset AF was reduced 45% with trandolapril in the TRACE study [62]. A sub-analysis of the SOLVD study showed a 78% reduction
of new onset AF with enalapril [46]. It is important to note
that both were placebo controlled studies, therefore, it is probable that the
antihypertensive effect of the ACE inhibitor contributed to the less incidence
of AF decreasing atrial pressure and left ventricular end diastolic pressure.
In this regard, the LIFE study showed that high systolic pressure is an
independent predictor of the development of new onset AF [61].
The LIFE study showed that patients with AF history had a reduction of 42% in
combined end point and cardiovascular morbidity and mortality, with a 45%
reduction in the risk of cerebrovascular accidents [63]. A
probable explanation of the benefit obtained with losartan, could be the
regression of atrial hypertrophy. Ventricular hypertrophy is an important
predictor of the development of new onset AF. Patients with left ventricular
hypertrophy have atrial enlargement, which is associated with an increased risk
of cerebrovascular accidents [64-67].
The pharmacological treatment of AF still remains a clinical challenge. The
ACE inhibitors and ARB agents have demonstrated a significant efficacy in
reducing the incidence of AF in HF and hypertensive patients. The relative
efficacy and safety of antiarrhythmic drugs over long periods of time limits
their usefulness in patients with congestive HF. Advance HF patients with AF
may be treated with amiodarone or dofetilide, but most other antiarrhythmic
drugs are unsuitable. The class III multichannel blockers appear to exert a
better performance in AF patients than other antiarrhythmic classes, and
dronedarone seems promising. The relatively high incidence of ventricular
arrhythmias and marked QT interval prolongation with some “pure” class III
antiarrhythmic agents limit their utilization for the therapeutic management of
AF. Therefore, the pharmacological treatment of AF still remains uncertain, and
requires careful and detailed evaluation from a safety perspective.
Despite the good results obtained with different drugs in the treatment
of HF, the optimal medical treatment can fail in the intention to improve symptoms
and quality of life of patients with severe HF. Thus, the necessity to use
cardiac devices emerges facing the failure of optimal medical treatment in
order to achieve hemodynamic improvement and correction of the physio-pathological
alterations. Patients with HF and complete left bundle branch block (LBBB)
commonly have an abnormal movement of the interventricular septum that is
related with interventricular dissynchrony and the resultant abnormal pressure
gradient between the two ventricles [68-70].
Due to this abnormal septal movement, there is an increase in the end systolic
diameter of the left ventricle and a decrease in regional septal ejection
fraction. Patients with LBBB with or without cardiac disease may show a
decrease global left ventricular ejection fraction, a decrease in cardiac
output, and dP/dt [70, 71]. In addition,
in cases of ventricular dissynchrony, the closure of the mitral valve may be
incomplete because atrial contraction is not followed by a time-adecuate
ventricular systole. If this delay is sufficiently long, a ventriculo-atrial
pressure gradient is generated which promotes mitral regurgitation in the early
phase of diastole. It is easy to imagine that ventricular dissynchrony in HF
patients puts the failing heart in additional mechanical disadvantage. By
placing pacing electrodes in the coronary sinus, the right ventricular apex,
and in the right atrial appendage (Figure 1), CRT can deliver simultaneous
electrical stimulation of both ventricles which results in a significant
hemodynamic improvement restoring a more homogeneous contraction pattern. Furthermore
CRT can adjust bi-ventricular stimulation (simultaneous, anticipated, or delayed)
to better synchronization. CRT can reduce the interventricular and
intraventricular mechanical dissynchrony produced by LBBB. It has been shown
that CRT increases the left ventricular filling time (Figure 2), decreases
septal dissynchrony and mitral regurgitation (Figure 3), allowing a hemodynamic
improvement [72-74]. These beneficial
hemodynamic changes are already seen in a few days and are followed by chronic
adaptations that allow long term benefits. Several longitudinal clinical
studies demonstrated beneficial effects of CRT in left ventricular remodeling [75-78]. There was a structural and
functional ventricular improvement during CRT. At 3 months, there was a
significant improvement in left ventricular ejection fraction, and a
significant decrease in end systolic and end diastolic volumes [75-78]. These beneficial effects are, apparently dependent on
continuous bi-ventricular stimulation since interruption of electric
stimulation produce a progressive but not immediate loss of effect. Therefore,
CRT reverts the ventricular reverse remodeling produced by chronic heart
failure, and it is suggested that improvement in mechanical synchrony is the predominant
mechanism. There are significant hemodynamic beneficial changes produced by CRT
that are clearly seen at the clinical level and outcome.
Figure 1: Catheter electrodes position during CRT. By placing pacing electrodes in the coronary sinus, the right ventricular apex, and in the right atrial appendage, CRT can deliver simultaneous electrical stimulation of both ventricles which results in a significant hemodynamic improvement restoring a more homogeneous contraction pattern.
|
Figure 2: Transmitral Pulse Wave Doppler Echocardiography. With the CRT device on, there is an increase and improvement in the left ventricular filling time.
|
Figure 3: Transmitral Color Doppler Echocardiography. With the CRT device on, there is a decrease in mitral regurgitation.
|
Various
studies have shown that CRT is beneficial to patients with HF in sinus rhythm [79-81]. However, CRT is interrupted in over
one-third after successful implantation of a CRT device, and the most common
reasons for interruption of CRT are the development of AF (18%) and loss of
left ventricular capture (10%) [82]. However, CRT can be
re-instituted in a high proportion of patients so that only 5% of patients who
successfully undergo implantation of a CRT device permanently lose adequate CRT.
About one third of patients do not respond to CRT for varying reasons, these
are the so called “non-responders”. Some have a complex coronary sinus anatomy
that does not allow adequate positioning of the electrode catheter. Others have
myocardial scars that do not respond to stimulation. Some other reasons are
related to the device itself [82-85].
Recent studies have also focused on the benefit of CRT to HF patients
with chronic AF, since these patients have substantially increased morbidity
and mortality [83]. These studies showed that patients with
AF may benefit from CRT as well [79-81, 84]. In this regard, Leon et al [84]
reported improved clinical parameters in 20 patients with chronic AF. In
particular the NYHA functional class improved by 29%, the quality of life by
33%, and the LV ejection fraction by 44%. Leclercq et al [81]
reported a 10% improvement in six minute walk distance in a substudy of the
MUSTIC trial, which is a randomized trial evaluating patients with AF. Kíes et
al [85] obtained similar results by showing significant
improvements in NYHA class, quality of life score, and six minute walk test after
six months of CRT. However, on an individual basis, 22% of their patients did
not respond to CRT, in line with studies of patients with sinus rhythm [85]. A significantly greater benefit was observed among
patients who had an AV node ablation. This may be explained by the fact that AV
node ablation ensures 100% ventricular capture, whereas 100% capture and rate
control are difficult to achieve with medical treatment [84,
86]. Even with optimized rate control in the non-ablated
patients, an average of only 81% ventricular pacing during CRT was obtained,
which is not good enough to deliver optimal CRT.
Almost one fifth of patients who undergo successful implantation of a
defibrillator capable of delivering CRT experience an AF with a rapid
ventricular response, which at least temporarily results in the inability to
deliver adequate CRT. Predictors of interruption of CRT as the result of the
development of AF in the HF population include a previous history of AF, a
relatively slow resting heart rate, and the absence of therapy with both beta-blockers
and ACE inhibitors [83]. These findings are consistent with
a recent analysis of the SOLVD study which found that treatment with enalapril
markedly reduces the risk of development of AF in patients with left
ventricular dysfunction [78]. Therefore, although it is not
clear whether the use of both beta-blockers and ACE inhibitors directly
influence the effectiveness of CRT, their use appears to improve the ability to
deliver CRT.
Implantable
atrial pacemakers and defibrillators can significantly decrease the incidence
of AF and also improve quality of life. These implantable devices have an
important role in the treatment of AF, particularly in association with other
treatments [87]. It is clear to see that prevention of AF
will improve the ability to deliver CRT, and these implantable devices play an
important role to achieve this goal. In this regard, it is useful the atrial
fibrillation suppression algorhythm (AFSA) in dual-chamber permanent pacemakers
[88]. It was stated that the AFSA is a stimulation parameter
designed specifically to suppress AF. It eliminates the unnecessary rapid
stimulation produced by the pacemaker associated to the fixed overdrive
stimulation when the patient is at rest. AFSA even performs the overdrive
stimulation when the intrinsic atrial rate of the patient increases in response
to physical activity (Table 1). It is a valuable tool to apply to paroxysmal
and persistent AF in selected patients that need a permanent pacemaker [88].
Table 1: The benefits of the atrial fibrillation suppression algorithm
|
Patients in AF do not have AV synchrony, thus it is
not possible to perform a synchronized pacing with adequately programmed AV
intervals [88-91]. Therefore, the
efficacy of CRT is compromised since adequate capture of biventricular pacing
can not be guaranteed. In addition, since AF patients usually have a consistent
or intermittent rapid ventricular rate, they require higher pacing rates.
Higher pacing rates are not constantly effective because of fused or
pseudo-fused ventricular complexes making the percentage of capture inexact,
which leads to overestimation of effective CRT capture. It is required an
almost maximal and complete biventricular capture to assure an optimal CRT
response [81]. The exact treatment of patients with AF
undergoing CRT is unclear; concomitant AV node ablation has been proposed to
avoid non-capture of pacing during AF. AV node ablation in this setting may be
an interesting way of controlling the cardiac rate and reliably delivering CRT
(Table 2). On the other hand, it has been suggested that patients may return to
sinus rhythm after a certain period of time with CRT, making AV node ablation
unnecessary. However, it is unclear whether patients with chronic AF will
revert to sinus rhythm after CRT. In this regard, Kíes et al [85]
found in patients with severe HF and chronic AF that CRT improved symptoms,
exercise capacity, systolic LV function, and LV reverse remodeling. In
addition, left atrial reverse remodeling was observed in this patient
population. However, these beneficial atrial changes did not restore sinus
rhythm in patients with HF with concomitant AF. These findings suggest that AV
node ablation should be considered for patients with chronic AF undergoing CRT.
There should be a strong effort to prevent AF, since it would significantly
improve the ability to deliver CRT in patients with HF. Because patients with
slower heart rates are more likely to develop AF, a dual-chamber rate-modulated
pacing mode (DDDR) may reduce interruptions of CRT. On the other hand, the
search for better pharmacological maneuvers to maintain sinus rhythm should
continue to provide the help needed to cardiac devices. The incorporation of
the AF suppression algorhythm to CRT devices may be very useful in eliminating
AF, allowing a better performance of the CRT device without interruption [86].
Table 2: Benefits of AV nodal ablation in CRT for HF and atrial fibrillation
|
The MUSTIC AF trial [81],
the OPSITE trial [92], and the PAVE trial [93]
are the only randomized CRT trials that permitted enrollment of AF patients who
underwent AV nodal ablation. The MUSTIC AF trial enrolled patients with
persistent AF of at least 3 months duration with spontaneous or induced slow
ventricular rate [81]. Most of the patients had slow
ventricular rates induced by AV node ablation. These AF patients with slow
ventricular rate have a higher grade of ventricular capture and CRT efficacy. The
“intention-to-treat” analysis did not find a significant difference in the
primary end point: 6 min walking test. This is probably due to the small sample
size, and to the fact that only 39 out of 64 patients completed the cross over
phase. Nevertheless, this trial demonstrated a positive trend in the secondary
end points, namely, NYHA functional class, quality of life, hospitalization for
worsening HF, and oxygen consumption. However, this positive trend became
statistical significant when only patients with 85% or more biventricular
stimulation percentage was included. These patients had significantly left
ventricular reverse remodeling. The OPSITE trial [92] had a
heterogeneous population, and was also strongly limited by a high percentage of
drop-out (32%). Therefore, it only showed a modest effect on quality of life and
exercise capacity in patients with CRT and AV node ablation. The PAVE trial
demonstrated at 6 months of follow-up that patients with CRT and AV node
ablation had significantly increased exercise capacity, quality of life, and
left ventricular ejection fraction [93]. A recent observational
study [94] with 673 consecutive patients treated with CRT
enrolled 114 AF patients. Only 42% of these AF patients had an adequate
biventricular capture despite optimal medical treatment and optimal pacing
programming. Therefore, these patients underwent AV node ablation. The final
results showed that only the patients with AV node ablation had evidence of
reverse remodeling, increased ejection fraction, decreased left ventricular
volumes, and improved clinical functional status. In an extension of this study,
a much larger multi-center, observational study [95], Gasparini
et al demonstrated in HF patients with permanent AF, that AV node ablation, in
addition to CRT, improves long-term overall mortality primarily by reducing HF
deaths. Although promising and inspiring, this result comes from a
non-randomized study, therefore, well designed and controlled prospective
randomized trials are necessary to further confirm these findings.
The results of several randomized trials demonstrated
that CRT devices improve HF symptoms and decrease mortality when the optimal
medical treatment fails in severe HF patients. It was demonstrated in patients
with permanent AF and CRT that AV node ablation permitted an effective biventricular
capture allowing the beneficial effect of CRT. The AV node ablation turns the
patient pacemaker-dependent, and allows a complete and consistent CRT without
fusion or pseudo-fusion, with a regular cardiac rhythm. AV node ablation, in
addition to CRT, improves long-term overall mortality primarily by reducing HF
deaths in patients with severe congestive HF and chronic AF. Although promising
and inspiring, this result comes from a non-randomized study, therefore, well
designed and controlled prospective randomized trials are necessary to further
confirm these findings. In the meanwhile, detailed individual evaluation of our
HF patients based on scientific evidence will provide us with the best
therapeutic decision making for each particular case.
-
Carson PE, Johnson GR, Dunkman WB, et al. The influence of atrial fibrillation on prognosis
in mild to moderate heart failure: The V-HeFT studies. Circulation 1993;87:
102VI-110VI.
-
Middlekauff HR, Stevenson WG, Stevenson LW. Prognostic significance of atrial fibrillation
in advance heart failure: A study of 390 patients. Circulation 1991;84:40-48.
-
Pozzoli M, Cioffi G, Traversi E, et al. Predictors of primary atrial fibrillation and
concomitant clinical and hemodynamic changes in patients with chronic heart failure: A
prospective study in 344 patients with baseline sinus rhythm. J Am Coll Cardiol
1998;32:197-204.
CrossRef
PubMed
-
Dries DL, Exner DV, Gersh BJ, et al. Atrial fibrillation is associated with an increased
risk for mortality and heart failure progression in patients with asymptomatic and
symptomatic left ventricular systolic dysfunction: A retrospective analysis of the SOLVD
trials. J Am Coll Cardiol 1998;32:695-703.
CrossRef
PubMed
-
Bourassa MG, Gurné O, Bangdiwala SI, et al. Natural history and patterns of current practice
in heart failure. J Am Coll Cardiol 1993;22:14A-19A.
-
Mathew J, Hunsberger S, Fleg J, et al. Incidence, predictive factors, and prognostic
significance of supraventricular tachyarrhythmias in congestive heart failure. CHEST
2000;118:914-922.
CrossRef
PubMed
-
Kannek WB, Abbot RD, Savage DD, et al. Epidemiologic features of chronic atrial
fibrillation: The Framingham study. N Engl J Med 1982;306:1018-1022.
-
Davies M.J., Pomerance A. Pathology of atrial fibrillation in man. Br Heart J 1972;
34:520-25.
CrossRef
-
Lev M. Aging changes in the human sinoatrial node. J Geront 1954; 9:1.
-
Davies M.J., Pomerance A. Quantitative study of aging changes in the human sinoatrial node
and internodal tracts. Br Heart J 1972; 34:150-152.
CrossRef
-
Hudson REB. The human pacemarker and its pathology. Br Heart J 1960; 22: 153.
CrossRef
-
Centurion O.A., Fukatani M., Konoe A., Tanigawa M., Shimizu A., Isomoto S., Kaibara M.,
Hashiba K. Different distribution of abnormal endocardial electrograms within the right
atrium in patients with sick sinus syndrome. Br Heart J 1992; 68: 596-600.
CrossRef
-
Rensma PL, Allessie MA, Lammers WJ, Bonke FI, Schalij MJ. Length of excitation wave and
susceptibility to reentrant atrial arrhythmias in normal conscious dogs. Circ Res
1988;62:395-410.
-
Wiener N, Rosenblueth A. The mathematical formation of the problem of conduction of impluses
in a network of connected excitable elements, specifically in cardiac muscle. Arch Inst
Cardiol Mex 1946;16:205-265.
-
Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation:
a study in awake chronically instrumented goats. Circulation 1995;92:1954 –1968.
-
Gaspo R, Bosch RF, Talajic M, et al. Functional mechanisms underlying tachycardia-induced
sustained atrial fibrillation in a chronic dog model. Circulation 1997;96:4027– 4035.
-
Li D, Fareh S, Leung TK, et al. Promotion of atrial fibrillation by heart failure in dogs:
atrial remodeling of a different sort. Circulation 1999;100:87–95.
-
Sanders P, Morton JB, Davidson NC, et al. Electrical remodeling of the atria in congestive
heart failure: Electrophysiological and electroanatomic mapping in humans. Circulation
2003;108:1461-1468.
CrossRef
PubMed
-
Erickson E.E., Lev M. Aging changes in the human AV node, bundle and bundle branches. J
Gerontol 1952; 7: 1.
-
Spach M. S., Dober P. C. Anderson P. A. W. Multiple regional differences in cellular
properties that regulate repolarization and contraction in the right atrium of adult and
newborn dogs. Circ Res 1989; 65: 1594-1611.
-
Spach M. S., Dober P. C. Relating extracellular potentials and their derivatives to
anisotropic propagation at microscopic level in human cardiac muscle. Evidence for
electrical uncoupling of side-to-side fiber connections with increasing age. Circ Res 1986;
58: 356-371.
-
Escande D, Coulombe A, Faibre JF, et al. Two types of transient outward currents in adult
human atrial cells. Am J Physiol 1987;252:142H-148H.
-
Ohtani K, Yutani C, Nagata S, et al. High prevalence of atrial fibrosis in patients with
dilated cardiomyopathy. J Am Coll Cardiol 1995;25:1162–1169.
CrossRef
PubMed
-
Ausma J, Wijffels M, Thone F, et al. Structural changes of atrial myocardium due to
sustained atrial fibrillation in the goat. Circulation 1997;96:3157–3163.
-
Van wagoner DR, Pond AL, McCarthy PM, et al. Outward K+ current densities and Kv 1.5
expression are reduced in chronic human atrial fibrillation. Circ Res 1997;80:772-781.
-
Fleg JL, Dhirenda ND, Lakatta EG. Right bundle branch block: Long term prognosis in
apparently healthy men. J Am Coll Cardiol 1983;1:887-892.
-
Fleg JL, Kennedy HL. Cardiac arrhythmias in a healthy elderly population. CHEST
1982;81:302-307.
CrossRef
PubMed
-
Tresh DD, Fleg JL. Unexplained sinus bradycardia: Clinical significance and long-term
prognosis in apparently healthy persons older than 40 years. Am J Cardiol 1986;58:1009-1013.
CrossRef
PubMed
-
Maurer MS, Shefrin EA, Fleg JL. Prevalence and prognostic significance of exercise induced
supraventricular tachycardia in apparently healthy volunteers. Am J Cardiol 1995;75:788-792.
CrossRef
PubMed
-
Centurion OA, Isomoto S, Shimizu A, Konoe A, Kaibara M, Hirata T, Hano O, Sakamoto R, Hayano
M, Yano K. The effects of aging on atrial endocardial electrograms in patients with
paroxysmal atrial fibrillation. Clin Cardiol 2003;26:435-438.
CrossRef
PubMed
-
Centurión OA, Shimizu A, Isomoto S, et al. Influence of advancing age on fractionated right
atrial endocardial electrograms. Am J Cardiol 2005; 96:239-242.
CrossRef
PubMed
-
Shimizu A, Centurión OA. Electrophysiological properties of the human atrium in atrial
fibrillation. Cardiovasc Res 2002;54:302-314.
CrossRef
PubMed
-
Centurión OA, Shimizu A, Isomoto S, Konoe A. Mechanisms for the genesis of paroxysmal atrial
fibrillation in the Wolff-Parkinson-White syndrome: Intrinsic atrial muscle vulnerability
vs. electrophysiological properties of the accessory pathway. Europace 2008;10:294-302.
CrossRef
PubMed
-
Moe GK, Rheinbolt WC, Abildskov IA. A computer model of atrial fibrillation. Am Heart J
1964;67:200-220.
CrossRef
PubMed
-
Alessie MA, Lammers WJEP, Bonke FIM. Experimental evaluation of Moe’s multiple wavelet
hypothesis of atrial fibrillation. In DP Zipes, J Jalife (eds): Cardiac electrophysiology
and arrythmias. Orlando, FL, Grune & Stratton, 1985, pp 265-275.
-
Tsuji H, Fujiki A, Tani M, et al. Quantitative relationship between atrial refractoriness
and the dispersion of refractoriness in atrial vulnerability. PACE 1992;15:403-410.
CrossRef
PubMed
-
Hashiba K, Centurión OA, Shimizu A: Electrophysiologic Properties of the human atrial muscle
in paroxysmal atrial fibrillation. Am Heart J 1996;131:778-789.
CrossRef
PubMed
-
Centurión OA, Isomoto S, Fukatani M, Shimizu A, Hirata T, Hano O, Konoe A, Tanigawa M,
Kaibara M, Sakamoto R, Yano K: Relationship between atrial conduction defects and
fractionated atrial endocardial electrograms in patients with sick sinus syndrome. PACE
1993; 16:2022-2033.
CrossRef
PubMed
-
Centurión OA, Shimizu A, Isomoto S, Konoe A, Hirata T, Kaibara M, Yano K: Repetitive atrial
firing and fragmented atrial activity elicited by extrastimuli in the sick sinus syndrome
with and without abnormal atrial electrograms. Am J Med Sciences 1994; 307(4):247-254.
-
Centurión OA, Isomoto S, Shimizu A, Konoe A, Hirata T, Kaibara M, Hano O, Yano K:
Supernormal atrial conduction and its relation to atrial vulnerability and atrial
fibrillation in patients with sick sinus syndrome and paroxysmal atrial fibrillation. Am
Heart J 1994; 128:88-95.
CrossRef
PubMed
-
Centurión OA, Shimizu A, Isomoto S, Konoe A. Mechanisms for the genesis of paroxysmal atrial
fibrillation in the Wolff-Parkinson-White syndrome: Intrinsic atrial muscle vulnerability
vs. electrophysiological properties of the accessory pathway. Europace 2008;10:294-302.
CrossRef
PubMed
-
Centurión OA, Konoe A, Isomoto S, Hayano M, Yano K: Possible role of Supernormal atrial
conduction in the genesis of atrial fibrillation in patients with idiopathic paroxysmal
atrial fibrillation. CHEST 1994; 106:842-847.
CrossRef
PubMed
-
Li D, Shinagawa K, Pang L, et al. Effects of angiotensin converting enzime inhibition on the
development of the atrial fibrillation substrate in dogs with ventricular
tachypacing-induced congestive heart failure. Circulation 2001;104:2608-2614.
CrossRef
PubMed
-
Nakashima H, Kumagai K, Urata H, et al. Angiotensin II antagonist prevents electrical
remodeling in atrial fibrillation. Circulation 2000;101:2612-17.
-
Madrid AH, Bueno MG, Rebollo MG, et al. Use of irbesartan to maintain sinus rhythm in
patients with long-lasting persistent atrial fibrillation. Circulation 2002;106:331-336.
CrossRef
PubMed
-
Goette A, Arndt M, Rocken C, et al. Regulation of angiotensin II receptor subtypes during
atrial fibrillation in humans. Circulation 2000;101:2678-2681.
-
Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, Massie BM, Colling C,
Lazzeri D. Amiodarone in patients with congestive heart failure and asymptomatic ventricular
arrhythmia. Survival trial of antiarrhythmic therapy in congestive heart failure. N Engl J
Med 1995; 333: 77-82.
CrossRef
PubMed
-
Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson
J, Johnson G, McNulty SE, Clapp-Channing N, Davidson- Ray LD, Fraulo ES, Fishbein DP, Luceri
RM, Ip JH, Sudden Cardiac Death in Heart Failure Trial (SCDHeFT) Investigators. Amiodarone
or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med
2005; 352: 225-237.
CrossRef
PubMed
-
Singh BN, Singh SN, Reda DJ, Tang XC, Lopez B, Harris CL, Fletcher RD, Sharma SC, Atwood JE,
Jacobson AK, Lewis HD Jr, Raisch DW, Ezekowitz MD; Sotalol Amiodarone Atrial Fibrillation
Eficacy Trial (SAFE-T) Investigators. Amiodarone versus sotalol for atrial fibrillation. N
Engl J Med 2005;352:1861–1872.
CrossRef
PubMed
-
Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, KusT, Lambert J, Dubuc M,
Gagne P, Nattel S, Thibault B, for the Canadian Trial of Atrial Fibrillation Investigators.
Amiodarone to prevent recurrence of atrial fibrillation. N Engl J Med 2000;342:913–920.
CrossRef
PubMed
-
Zehender M, Hohnloser S, Mu¨ller B, Meinertz T, Just H. Effects of amiodarone versus
quinidine and verapamil in patients with chronic atrial fibrillation: results of a
comparative study and a 2-year follow-up. J Am Coll Cardiol 1992;19:1054–1059.
-
Juul-Moller S, Edvardsson N, Rehnqvist-Ahlberg N. Sotalol versus quinidine for the
maintenance of sinus rhythm after direct current conversion of atrial fibrillation.
Circulation 1990;82:1932–1939.
-
Benditt DG, Williams JH, Jin J, Deering TF, Zucker R, Browne K, Chang-Sing P, Singh BN, for
the D,L-Sotalol Atrial Fibrillation/Flutter Study Group. Maintenance of sinus rhythm with
oral D,L-sotalol therapy in patients with symptomatic atrial fibrillation and/or atrial
flutter. Am J Cardiol 1999;84:270–277.
CrossRef
PubMed
-
Singh S, Saini RK, DiMarco JP, Kluger J, Gold R, Chen YW. Efficacy and safety of sotalol in
digitalized patients with chronic atrial fibrillation. The Sotalol Study Group. Am J Cardiol
1991;68:1227–30.
CrossRef
PubMed
-
Singh BN, Connolly SJ, Crijns HJM, Roy D, Kowey PR, Capucci A, Radzik D, Aliot, EM Hohnloser
SH, for the EURIDIS and ADONIS Investigators. Dronedarone for Maintenance of Sinus Rhythm in
Atrial Fibrillation or Flutter. N Engl J Med 2007;357:987-99.
CrossRef
PubMed
-
Lombardi F, Borggrefe M, Ruzyllo W, and Lu¨deritz B for the A-COMET-II Investigators
Azimilide vs. placebo and sotalol for persistent atrial fibrillation: the A-COMET-II
(Azimilide-Cardioversion Maintenance Trial-II) trial. Eur Heart J 2006;27:2224–2231.
CrossRef
PubMed
-
Torp-Pedersen C, Moller M, Bloch-Thomsen PE, Kober L, Sandoe E, Egstrup K, Agner E, Carlsen
J, Videbae J, Marchant B, Camm AJ. Dofetilide in patients with congestive heart failure and
left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on
Dofetilide Study Group. N Engl J Med 1999;341:857–865.
CrossRef
PubMed
-
Singh S, Zoble RG, Yellen L, Brodsky MA, Feld GK, Berk M, Billing CB Jr. Eficacy and safety
of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic
atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative
research on dofetilide (SAFIRE-D) study. Circulation 2000;102:2385–2390.
-
Camm AJ, Pratt CM, Schwartz PJ, Al-Khalidi HR, Spyt MJ, Holroyde MJ, Karam R, Sonnenblick
EH, Brum JM; Azimilide post infarct survival evaluation (ALIVE) Investigators. Mortality in
patients after a recent myocardial infarction: a randomized, placebo-controlled trial of
azimilide using heart rate variability for risk stratification. Circulation
2004;109:990–996.
CrossRef
PubMed
-
Singer I, Al-Khalidi H, Niazi I, Tchou P, Simmons T, Henthorn R, Holroyde M, Brum J.
Azimilide decreases recurrent ventricular tachyarrhythmias in patients with implantable
cardioverter defibrillators. J Am Coll Cardiol 2004;43:39–42.
CrossRef
PubMed
-
Wachtell K, Lehto M, Gerdts E, et al. Angiotensin II receptor blockade reduces new-onset
atrial fibrillation and subsequent stroke compared to atenolol: The losartan intervention
for end point reduction in hypertension (LIFE) study. J Am Coll Cardiol 2005;45:712-719.
CrossRef
PubMed
-
Pedersen OD, Bagger H, Kober L, et al. Trandolapril reduces the incidence of atrial
fibrillation after acute myocardial infarction in patients with left ventricular
dysfunction. Circulation 1999;100:376-80.
-
Wachtell K, Hornestam B, Lehto M, et al. Cardiovascular morbidity and mortality in
hypertensive patients with a history of atrial fibrillation: The losartan intervention for
end point reduction in hypertension (LIFE) study. J Am Coll Cardiol 2005;45:705-711.
CrossRef
PubMed
-
Gerdts E, Oikarinen L, Palmieri V, et al. Correlates of left atrial size in hypertensive
patients with left ventricular hypertrophy: The losartan intervention for end point
reduction in hypertension (LIFE) study. Hypertension 2002;39:739-43.
CrossRef
PubMed
-
Fuster V, Ryden LE, Asinger RW, et al. ACA/AHA/ESC guidelines for the management of patients
with atrial fibrillation. J Am Coll Cardiol 2001;38:1231-66.
CrossRef
PubMed
-
Benjamin EJ, D’Agostino RB, Belanger AJ, et al. Left atrial size and the risk of stroke and
death. The framingham heart study. Circulation 1995;92:835-41.
-
Gottdiener JS, Reda DJ, Williams DW, et al. Effect od single-drug therapy on reduction of
left atrial size in mild to moderate hypertension: Comparison of six antihypertensive
agents. Circulation 1998;98:140-8.
-
Grines CL, Bashore TM, Boudoulas H, et al. Functional abnormalities in isolated left bundle
branch block. The effect of interventricular asyncrony. Circulation 1999;79:845-853.
-
Wyndham CR, Smith T, Meeran MK, et al. Epicardial activation in patients with left bundle
branch block. Circulation 1980;61:696-703.
-
Takeshita A, Basta LL, Kioschos JM. Effect of intermittent left bundle branch block on left
ventricular performance. Am J Med 1974;56:251-255.
CrossRef
PubMed
-
Bramlet DA, Morris KG, Coleman RE, et al. Effect of rate-dependent left bundle branch block
on global and regional left ventricular function. Circulation 1983;67:1059-1065.
-
Kass DA, Chen CH, Curry C, et al. Improved left ventricular mechanics from acute VDD pacing
in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation
1999;99:1567-73.
-
Auricchio A, Stellbrink C, Block M, et al. Effect of pacing chamber and atrioventricular
delay on acute systolic function of paced patients with congestive heart failure. The Pacing
Therapies for Congestive Heart Failure Study Group. The Guidant Congestive Heart Failure
Research Group. Circulation 1999;99:2993-3001.
-
Francis GS, Cohn JN, Johnson G, et al. Plasma norepinefrine, plasma renine activity, and
congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II. The
V-HeFT VA Cooperative Studies Group. Circulation 1993;87(6):VI40-VI48.
-
Adamson PB, Kleckner K, Van Hout WL, et al. Cardiac resynchronization therapy improves heart
rate variability in patients with symptomatic heart failure. J Am Coll Cardiol
2003;108:266-269.
-
Yu CM, Chau E, Sanderseon JE, et al. Tissue Doppler echocardiographic evidence of reverse
remodeling and improved synchronicity by simultaneously delaying regional contraction after
biventricular pacing therapy in heart failure. Circulation 2002;105:438-445.
CrossRef
PubMed
-
Knight BP, Desai A, Coman J, et al. Long-term retention of cardiac resynchronization
therapy. J Am Coll Cardiol 2004;44:72-77.
CrossRef
PubMed
-
Vermes E, Tardif JC, Bourassa MG, et al. Enalapril decreases the incidence of atrial
fibrillation in patients with left ventricular dysfunction. Insight from the SOLVD study.
Circulation 2003;107:2926-31.
CrossRef
PubMed
-
Molhoek SG, Bax JJ, Bleeker GB, et al. Comparison of response to cardiac resynchronization
therapy in patients with sinus rhythm versus chronic atrial fibrillation. Am J Cardiol
2004;94:1506–9.
CrossRef
PubMed
-
Linde C, Leclercq C, Rex S, et al. Long-term benefits of biventricular pacing in congestive
heart failure: results from the multisite stimulation in cardiomyopathy (MUSTIC) study. J Am
Coll Cardiol 2002;40:111–118.
CrossRef
PubMed
-
Leclercq C, Walker S, Linde C, et al. Comparative effects of permanent biventricular and
right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur
Heart J 2002;23:1780–1787.
CrossRef
PubMed
-
Rivero-Ayerza M, Scholte op Reimer W, Lenzen M, Theuns DAMJ, Jordaens L, Komajda M, Follath
F, Swedberg K, Cleland JGJ. New-onset atrial fibrillation is an independent predictor of
in-hospital mortality in hospitalizad heart failure patients: results of the EuroHeart
Failure Survey. Eur Heart J 2008;29:1618–1624.
CrossRef
PubMed
-
Dries DL, Exner DV, Gersh BJ, et al. Atrial fibrillation is associated with an increased
risk for mortality and heart failure progression in patients with asymptomatic and
symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD
trials. Studies of left ventricular dysfunction. J Am Coll Cardiol 1998;32:695–703.
CrossRef
PubMed
-
Leon AR, Greenberg JM, Kanuru N, et al. Cardiac resynchronization in patients with
congestive heart failure and chronic atrial fibrillation: effect of upgrading to
biventricular pacing after chronic right ventricular pacing. J Am Coll Cardiol
2002;39:1258–63.
CrossRef
PubMed
-
Kiès P, Leclercq C, Bleeker GB, Crocq C, Molhoek SG, CPoulain C, van Erven L, Bootsma M,
Zeppenfeld K, van der Wall EE, J-C, Daubert JC, MJ, Schalij MJ and Bax JJ. Cardiac
resynchronisation therapy in chronic atrial fibrillation: impact on left atrial size and
reversal to sinus rhythm. Heart 2006;92;490-494.
-
Van Gelder MB, Meijer A, Bracke FA. Stimulation rate and the optimal interventricular
interval during cardiac resynchronization therapy in patients with chronic atrial
fibrillation. PACE 2008;31:569–574.
CrossRef
PubMed
-
Cooper JM, Katcher MS, Orlov MV. Implantable devices for the treatment of atrial
fibrillation. N Engl J Med 2002;346:2062-2068.
CrossRef
PubMed
-
Gauch P. Atrial fibrillation suppression algorithm in dual-chamber permanent pacemakers. Rev
Soc Parag Cardiol 2005;3:141-145.
-
Bradley DJ, Shen WK. Atrioventricular junction ablation combined with either right
ventricular pacing or cardiac resynchronization therapy for atrial fibrillation: The need
for large-scale randomized trials. Heart Rhythm 2007;4:224–232.
CrossRef
PubMed
-
Herweg B, Ilercil A, Madramootoo C, Ali R, Barold SS. AV Junctional Ablation Allowing More
Effective Delivery of Cardiac Resynchronization Therapy in Patients with Intra- and
Interatrial Conduction Delay. PACE 2008;31:685–690.
CrossRef
PubMed
-
Leclercq C, Mabo P. Cardiac resynchronization therapy and atrial fibrillation. Do we have a
final answer? Eur Heart J 2008;29:1597–1599.
CrossRef
PubMed
-
Brignole M, Gammage M, Paggioni E, et al. Comparative assessment of right, left, and
biventricular pacing in patients with permanent atrial fibrillation Eur Heart J
2005;26:712-722.
CrossRef
PubMed
-
Doshi RN, Daoud EG, Fellows C, et al. Left ventricular-based cardiac stimulation post AV
nodal ablation evaluation (The PAVE study). J Cardiovasc Electrophysiol 2005;16:1160-1165.
CrossRef
PubMed
-
Gasparini M, Auricchio A, Regoli F, et al. Four-year efficacy of cardiac resynchronization
therapy on exercise tolerance and disease progression: The importance of performing
atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol
2006;48:734-743.
CrossRef
PubMed
-
Gasparini M, Auricchio A, Metra M, Regoli FO, Fantoni C, Lamp B, Curnis A, Vogt J, Klersy C,
The MILOS group. Long-term survival in patients undergoing cardiac resynchronization
therapy: the importance of performing atrio-ventricular junction ablation in patients with
permanent atrial fibrillation. Eur Heart J 2008;29:1644–1652.
CrossRef
PubMed