Corresponding Address: Dr. Calambur Narasimhan, Chief of Electrophysiology, CARE Hospital, Road No 1, Banjara Hills, Hyderabad – 500034, India.
AF is a common arrhythmia
associated with large burden of morbidity and mortality [1].
In areas with a high prevalence of rheumatic heart disease, valve disease is
the most common substrate for the occurrence of AF and this problem assumes greater importance because the resulting escalation in morbidity and mortality involves relatively younger population. As is true of the general population, the prevalence of AF in patients with rheumatic mitral valve disease (RMVD) increases with advancing age. When compared to patients with mitral valve disease without AF, those with AF are at a higher NYHA class, have more severe left ventricular dysfunction and show greater left atrial enlargement. Mitral valve is the most
commonly involved valve among patients with AF with valvular heart disease.
Mitral stenosis, Mitral regurgitation and Tricuspid regurgitation comprise 70%
of valvular heart disease related to AF. Diker et al in an Echo Doppler study
had found AF in 29% of patients with isolated mitral stenosis, in 16% with isolated
mitral regurgitation, in 52% in combined mitral stenosis and regurgitation but
in only 1% of patients with aortic valvular disease [2].
While the mechanisms of non-valvular AF have been extensively studied, the literature is sparse concerning pathophysiological
mechanisms leading to AF in patients with underlying valvular diseases. There
are apparent differences in the pathological findings in these two subsets of
patients. Occurrence of AF is known to correlate with LA size ; the incidence
of AF rises from 3% when the left atrial diameter is 40mm to 54% if the
left atrial diameter is 40 mm [3]. Mitral valve disease
is associated with large left atria, and the elevated left atrial pressure causes
myocardial stretch, which in turn results in slow conduction velocities,
increased dispersion of refractoriness and increased automaticity, all of which
create the milieu for initiating and perpetuating sustained AF.
A large postmortem study on patients with AF and associated organic heart
disease showed a spectrum of histologic abnormalities that diffusely involved
both the right and left atria. It was postulated that fibrosis and degeneration
of the atrial myocardium in valvular heart disease, especially those of
rheumatic etiology, disturb impulse propagation in the atria and lead to AF [4]. Atrial fibrosis probably contributes to persistent AF after balloon
valvuloplasty or surgical valve replacement and repair. AF also occurs more
frequently when mitral valve is calcified or is prolapsing [5].
An insight into the role of substrate in perpetuation of AF in patients
with mitral stenosis was provided in an elegant study by Fan et al [6]. The regional ERPs in the atria increased after mitral
valvuloplasty in patients with sinus rhythm and in AF; but in those with AF the
increase was heterogenous, while in those with sinus rhythm it was homogenous.
A study of a small group of patients with rheumatic AF, who had undergone
balloon mitral valvuloplasty, had revealed that there was an organized atrial activity
most often at the Os of the Coronary Venous Sinus preceding initiation of AF,
with no evidence of focal firing from the pulmonary veins [7].
Intuitively,
left atrial mapping in these patients should throw light on the substrate
perpetuating the fibrillation. However, literature is sparse in this regard. In
our small series, the electroanatomic maps showed extensive left
atrial scarring of diverse patterns. [Fig 1]. The
significance of this finding remains speculative at this point and merits
further investigation.
Figure 1: Schematic diagram showing the varied scar pattern in the 5 rheumatic AF patients
who underwent ablation. The overlap in numbers is due to patients having scar in more than one area. scars are coloured in red.
|
While the exact mechanism of development AF is yet to
be fully elucidated the impact of it on the patient, especially patients with
mitral stenosis has been studied. The impact almost entirely depends on the
ventricular rate. As the ventricular rate increases the diastole decreases,
therefore mitral flow increases. In MS increased mitral flow causes increased
left atrial and pulmonary venous pressure. The loss of atrial contraction per
se has minimal impact on the patient with significant MS. Unlike the situation
in normal patients, atrial contraction does not cause an increase in flow
across an obstructed mitral valve. This reflected as a loss of the A wave in
the M –mode in echocardiogram of MS patients who are in sinus rhythm [8].
Thrombo- Embolism and Anticoagulation
AF is a major cause of systemic thrombo-embolism and in patients over the age of 65 years, it is responsible for more than one-third of all strokes [9]. Advancing age, history of previous thromboembolic event, presence of mitral valve disease, congestive heart failure, enlarged left atrium, previous MI, hypertension and left atrial thrombus on transesophageal echocardiography predict occurrence of embolic strokes in patients with AF [10]. The presence of AF multiplies the risk of stroke 5 times in a patient with structurally normal heart, and increases by a factor of 17 in those with mitral
valvular disease. The lifetime recurrence rates for strokes in these patients
may be as high as 30%–75% [11]. The risk of recurrent
strokes appears to be similar with chronic and paroxysmal AF. Transesophageal
echocardiographic studies have shown that the presence of significant mitral
regurgitation is associated with a lower incidence of spontaneous echo contrast
in the left atrium and thus with a lower risk of thrombi and embolization as
compared to Rheumatic mitral stenosis [12]. A particular
study has demonstrated that 20% of patients with mitral stenosis and none with
mitral regurgitation show left atrial thrombi [13]. More
importantly, 28 of the 30 patients (93%) with atrial thrombi showed AF,
demonstrating the role of rhythm disturbance in the generation of left atrial
thrombus. In patients with mitral valve disease, thrombi are found not
only in the left atrial appendage but also in the body of the left atrium.
This is in contrast to nonvalvular AF in which thrombi form predominantly (90%)
in the left atrial appendage [14].
In a surgical clinicopathologic
study in patients with AF, the prevalence of left atrial clot with predominant
mitral regurgitation was 8.3% in comparison with 54% in patients with
predominant mitral stenosis (p < 0.0001) 12 In sinus rhythm, the prevalence
of left atrial clot was 0% in predominant mitral regurgitation and 14.3% in
patients with mitral stenosis (p < 0.001). None of the patients with AF and
severe mitral regurgitation had left atrial clot [12, 15].
All patients with Rheumatic AF
need to be anticoagulated in the absence of contraindications. The use and
timing of anticoagulation for patients in sinus rhythm with mitral stenosis is
still a moot point as the risk of thromboembolism is unrelated to the severity
of the disease. However, successful balloon valvuloplasty results in resolution
of echo contrast and decrease in thromboembolic risk [16].
Correction of the valvular lesion thus should be undertaken whenever
feasible. There are no dose-ranging trials to guide anticoagulant therapy in
patients with AF in valvular heart disease. Based on single-center studies in
patients with valvular disease and on the results of large multi-center studies
involving patients with AF of non-valvular etiology, however, similar
recommendations can be made.
The natural history of non-valvular AF is extremely variable. A good
number of patients with non-valvular AF have paroxysmal episodes for long
periods that become chronic or persistent in only a few. On the other hand, the
initial attacks of AF in valvular heart disease are paroxysmal, but almost
invariably progress to chronic AF. The symptoms are related to the irregular
and rapid ventricular rate, development of heart failure and thrombo-embolic
complications. These complications are related to the duration of AF and occur
more often in AF associated with valvular heart disease. While the treatment of
the underlying valvular disease is of primary importance, the management of the
arrhythmia is aimed at either control of ventricular rate without attempting to
restore sinus rhythm, or to restoration of sinus rhythm with follow-up
aggressive therapy to maintain it. As embolic complications are the major cause
of morbidity, chronic anticoagulant therapy is important in all patients with
AF and valvular heart disease.
Correction of underlying disorder
Treatment of the underlying valvular abnormality should be considered,
e.g. surgical repair or replacement of mitral or tricuspid valve in severe
regurgitant lesions, or valvuloplasty in mitral stenosis. However, in patients
with enlarged and dysfunctional atria, despite correction of the underlying
valvular lesion, AF often persists. As a general rule in all these patients
correction of reversible factors like thyrotoxicosis and alcohol intake must be
addressed.
Delayed correction of underlying disorder
would bring down the chance of maintaining these patients in sinus rhythm. This
is partly reflected in the American Heart Association practice guidelines. It
recommends mitral valve surgery in asymptomatic patients with severe MS as a
Class II b indication, if there is new onset AF. In patients with severe MR it
is a Class II a indication. However, this is based on consensus opinion and
not on substantial data [17].
Control of ventricular rate
The control of ventricular rate
is one of the main goals of the treatment of patients with all forms of AF when
sinus rhythm cannot be restored immediately. This strategy remains the mainstay
in patients with valvular heart disease as most of them have chronic AF not readily
amenable to rhythm conversion. Of the several drugs used Digitalis, which was
most often used earlier, is very often ineffective during exercise because its
electrophysiologic action is mediated largely through augmentation of vagal
tone on the AV node. Beta-blockers such as propranolol, metoprolol
and atenolol, as well as negative chronotropic calcium-channel blockers such as
verapamil and diltiazem, are effective agents for control of ventricular rate
with a low incidence of adverse effects [18]. Studies have
shown that combining digoxin and a beta-blocker that has intrinsic
sympathomimetic activity keeps ventricular rates at peak exercise low while
minimizing the effects of these drugs when heart rates are slowest, as is
usually seen during the night [18, 19].
Catheter ablation of the AV junction and implantation of a
rate-responsive ventricular permanent pacemaker should be considered in
drug-refractory patients or patients who cannot take beta-blockers and
calcium-channel blockers [20].
Rhythm Control
The clinical advantage of maintaining
patients in sinus rhythm following corrective procedures for mitral valvular
disease has been demonstrated in a few studies. Vaturi et al showed worse
functional class and increased transmitral gradients in patients with atrial
fibrillation compared to those in sinus rhythm following Mitral Replacement
Surgery [21].
In a study by Leon et al, patients with AF, BMV resulted in inferior immediate and long-term outcomes, as reflected in a smaller post-BMV mitral valve area (1.7
6 0.7 vs. 2 6 0.7 cm2; p, 0.0001) and a lower event free survival (freedom of
death, redo-PMV and mitral valve surgery) at a mean follow-up time of 60 months
(32% vs. 61%; p, 0.0001). AF by itself does not unfavorably influence the
outcome, but is a marker for clinical and morphologic features associated with
inferior results after PMV [22].
Maatouk et al compared outcomes
at ten years in a fairly large group of patients with and without AF who
underwent balloon mitral commissurotomy. They reported a lower ten year
survival and a lower ten year event free survival in the AF group. The AF group
also had higher rate of restenosis. However the cause of death were not
reported and the events described were reinterventions and mitral valve
replacements [23].
Rheumatic AF has also been shown to
increase the incidence of prosthetic valve thrombosis in a study that was primarily
looking at the results of thrombolytic therapy in patients with prosthetic valve
thrombosis [24].
In patients with valvular AF, conversion
and maintenance of sinus rhythm is difficult due to valvular abnormalities,
large left atria and the presence of unhealthy substrate. Cardioversion to
sinus rhythm may be achieved by chemical means or by electrical cardioversion.
Chemical agents are less effective as in most cases the AF is of long duration.
Antiarrhythmic agents of Vaughan Williams classes IA, IC or III are effective. Success rates in the range of 60% have been reported with flecainide,
propafenone and amiodarone [25, 26] Newer
class III agents such as intravenous ibutilide and intravenous or oral
dofetilide are most effective in atrial flutter and fibrillation of recent
onset. Short-term amiodarone with or without electrical cardioversion has
been shown to be effective in the restoration of sinus rhythm in chronic AF
after mitral valve surgery [25]. Prophylactic
use of oral amiodarone and sotalol has been shown to prevent AF immediately
following cardiac surgery [27].
The debate on preference of rate
over rhythm control that was addressed by the AFFIRM [28],
RACE [29], STAF [30] trials predominantly
involved non-valvular AF patients. These trials failed to demonstrate
superiority of rhythm control strategy. However further analysis of the
AFFIRM data showed that that the presence of AF was associated with a 47%
increased mortality compared with sinus rhythm and the use of an
antiarrhythmic medication was associated with a 49% increased mortality ,
suggesting that any mortality benefit from the maintenance of sinus rhythm was
offset by increased mortality from currently available antiarrhythmics [31]. The more recently published randomized trial
by Roy et al showed no benefit of rhythm control over rate control in patients
with LV dysfunction [32]. Non pharmacological methods,
that have evolved from the surgical to radiofrequency catheter based pulmonary
vein isolation with and without linear lesions have shown reasonable success in
maintenance of sinus rhythm [33] Trials
comparing these modalities against rate control need to be conducted for
determining the guidelines for the best modality of management.
Both pharmacological and
non pharmacological methods of conversion and maintenance of sinus rhythm which
have been studied in non- valvular AF have also been studied in
valvular/rheumatic AF albeit in smaller and less well conducted studies
Similar to non-valvular AF there is no conclusive data to determine the best
modality of management in rheumatic AF.
CRAAFT [34].
trial was a prospective study of 144 rheumatic valvular patients comparing rate
control (using Diltiazem) and Rhythm control (Amiodarone versus placebo).
Besides demonstrating a mortality benefit with rhythm control, the study showed
a improvement in NYHA class, quality of life and exercise capacity on
achievement of sinus rhythm. There was no difference in rates of
hospitalization or thromboembolism or bleeds between the two groups. In
contrast to the trials involving non- valvular AF, this study had individuals
of young age (mean age 39 yrs), and only those who sustained sinus rhythm at one
year (69%) were compared with the rate control group. The mortality observed
in the rate control arm was due to prosthetic valve thrombosis. The other major
limitation of the study was its small sample size, a dropout of 13% and a
relatively short follow up. Another study that compared both modalities in
patients undergoing balloon mitral valvuloplasty showed that the six minute
walk test improved significantly in patients in whom sinus rhythm was
maintained [35].
Maze surgery and its modifications have been successfully attempted by
many investigators to restore sinus rhythm in RVHD and atrial fibrillation patients
[36].
Patients undergoing mechanical valve replacement and concomitant AF
surgery, the incidence of stroke 5 years after surgery is lower than in those
who undergo mitral valve replacement alone [37, 38]. Although initial studies had shown insufficient rates of
sinus rhythm restoration (59%) for the Maze procedure in AF associated with
rheumatic valve disease [39], subsequent studies by other
investigators have shown comparable conversion rates with acceptable operative
risk to that of nonvalvular AF [36]. Patwardhan
et al [40] pioneered the technique of radiofrequency bipolar
maze for atrial fibrillation during valve surgery. There was 80% freedom from
atrial fibrillation at five months along with restoration of atrial transport
function. Guang et al [41] have also had similar experience
with radiofrequency maze during mitral valve surgery, with a longer follow up
of 3 years wherein 77% of patients remained in sinus rhythm. The outcome of
surgical maze for atrial fibrillation is similar in rheumatic and non-rheumatic
atrial fibrillation in terms of sinus rhythm achievement and restoration of
left-atrial function. Lee et al [42] showed that the maze
procedure is equally effective in AF of rheumatic and non rheumatic etiology in
terms of sinus conversion rate. Patwardhan’s group [43]
recently evaluated the efficacy of three different methods of ablative
procedures - biatrial lesions, left atrial lesions and pulmonary vein isolation
- and found them all comparable in a group of rheumatic patients.
It may be recommended that all patients with a history of AF undergo
concomitant AF surgery/ablation at the time of their valve procedure, if it can
be performed without adding significant morbidity to the procedure.
Multiple approaches for catheter
ablation of AF are under clinical investigation, and although preliminary
results are encouraging, indications, safety and long-term success are still
not well defined; it is particularly less well studied in rheumatic AF.
A small study among patients
with AF and rheumatic heart disease has shown that in a good number the
arrhythmia is a relatively organized rhythm with earliest atrial activity near
the os of the coronary sinus [7]. Catheter ablation in this
area was successful in restoring sinus rhythm in most of these patients. All
these patients were on amiodarone but details of long term follow up of these
patients are not available.
Furthermore
a recent study showed efficacy of Hybrid Therapy of Radiofrequency Catheter
Ablation and BMV in Patients with Atrial Fibrillation and Mitral Stenosis.Twenty consecutive patients with
drug-resistant AF and rheumatic MS underwent RFA combined with a BMV or
transthoracic direct cardioversion (DC) following a BMV. During a mean
follow-up period of 4.0 +/- 2.7 years, 8 patients (80%) in the RFA group were
maintained in SR, as compared to 1 (10%) in the DC group. However if this
efficacy translated into better clinical outcomes is not known [44].
In geographical regions where rheumatic
heart disease is prevalent AF is an important health care issue affecting
younger population. It significantly contributes to mortality and morbidity and
constitutes a burden on healthcare resources of the society.
The benefit of long term anticoagulation
is well established. Whether the rate control or rhythm control constitutes a
better strategy is not clearly determined in non-valvular AF. Compared to
patients with non-valvular AF maintenance of sinus rhythm in rheumatic AF
patients appears to be more beneficial, particularly among those undergoing
mitral valve surgery
However, the benefit of
restoring sinus rhythm are not clear in rheumatic heart disease patients who
are haemodynamically stable and do not require valvular surgery. Although small
studies have shown benefit in terms of functional class it remains to be seen
if it will significantly alter important clinical endpoints.
Pharmacological methods of
rhythm control have drawbacks and it appears prudent to compare
nonpharmacological methods of rhythm control against rate control, considering the
advancements of these modalities and their success rates in maintenance of
sinus rhythm.
Despite lack of large supportive
evidence it seems reasonable to attempt conversion to sinus rhythm in rheumatic
heart disease in patients undergoing corrective valve surgery. However the best
strategy of achieving it is not well established.
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