© 2004 by European Society of Cardiology
ORIGINAL ARTICLE
Assessment of upgrading to biventricular pacing in patients with right ventricular pacing and congestive heart failure after atrioventricular junctional ablation for chronic atrial fibrillation
Department of Cardiology, Brest University Hospital 29609 Brest Cedex, France
Manuscript submitted 15 December 2003. Accepted after revision 15 April 2004.
*Corresponding author. Tel.: +33-298-347392; fax: +33-298-347803. E-mail address: jean-jacques.blanc{at}univ-brest.fr (J.-J. Blanc).
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Abstract |
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AIMS: Effects of cardiac resynchronization therapy (CRT) in patients with right ventricular pacing and congestive heart failure (CHF) have only been reported in limited series. CRT in patients with atrial fibrillation remains controversial. Patients with AV junctional ablation offer a unique opportunity to study the effects of CRT in patients with right ventricular pacing combined with atrial fibrillation.
The aims of the present study were to evaluate the effects of upgrading to biventricular pacing patients with CHF, permanent atrial fibrillation, and prior ablation of the atrioventricular (AV) junction followed by conventional right ventricular pacing.
METHODS AND RESULTS: We studied 16 consecutive patients with permanent atrial fibrillation treated by AV junctional ablation. After a mean follow-up of 20±19 months (6 weeks to 5 years) they were successfully upgraded to biventricular pacing for severe CHF. Parameters were prospectively evaluated at baseline and at 6 months.
The 14 surviving patients at 6 months demonstrated significant improvement (P<0.02) in New York Heart Association class but the exercise test parameters remained unchanged. Cardiothoracic ratio decreased by 5% (P=0.04), end-systolic diameter by 8% (P=0.001), end-diastolic diameter by 4% (P=0.08), systolic pulmonary artery pressure by 17% (P<0.0001) and mitral regurgitation area by 40% (P<0.05). Ejection fraction increased by 17% (P=0.11) and fractional shortening by 24% (P=0.01).
CONCLUSION: CRT improves left ventricular performance and functional status in patients with permanent atrial fibrillation and prior remote right ventricular pacing.
Key Words: resynchronization, atrial fibrillation, congestive heart failure, atrioventricular junctional ablation
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Introduction |
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Atrioventricular (AV) junctional (nodal) ablation is an effective procedure to control ventricular rate in patients with chronic atrial fibrillation refractory to conventional pharmacological treatment and significantly improves their quality of life [1,
2]. In the majority of patients slowing the ventricular rate and restoring regularity is sufficient to improve palpitations and symptoms of congestive heart failure (CHF). In some patients this treatment has no or only limited effects and in others, after an asymptomatic period which may last several years, CHF has recurred, possibly favoured by the abnormal left ventricular (LV) activation sequence induced by permanent right ventricular pacing [3–5]. In such patients with pacing-induced left bundle branch block, cardiac resynchronization therapy (CRT) appears to be a logical and promising method to reverse the deleterious consequences of right ventricular pacing. However, effectiveness of CRT in patients with prior right ventricular pacing has not been clearly assessed and its effects in patients with atrial fibrillation and CHF remain a subject of debate: in some studies the results are similar to those observed in patients in sinus rhythm [6–8] while in others they are less relevant [9]. Patients with AV junctional ablation for permanent atrial fibrillation have both these conditions associated so they offer a unique opportunity to evaluate the efficacy of CRT in the presence of these two factors combined. |
Methods |
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Patient population
The study group comprised 16 consecutive patients with permanent atrial fibrillation who had successful AV junctional ablation followed by right ventricular apical rate-responsive pacing. In all these patients AV node ablation was performed after multiple pharmacological attempts to control ventricular rate. Study population comprised eight patients who did not have any symptoms of heart failure at the time of ablation but who developed overt CHF after a long asymptomatic period, and eight patients who had marked symptoms of CHF before ablation and who remained symptomatic while paced at the right ventricular apex for at least 6 weeks. Ablation improved functional status in the majority of patients. However, after a mean period of 20±19 months (range: 6 weeks to 5 years) they exhibited symptoms of severe CHF (New York Heart Association class III or IV) associated with marked systolic LV dysfunction (ejection fraction
35%) refractory to tailored standard medical treatment. In all these patients LV pacing was proposed, accepted and successfully implanted.
Follow-up
In this prospective study, patients were systematically evaluated at 1 month, 6 months, and every 6 months thereafter. In order to have homogeneous data only the results observed at the 6-month follow-up visit are reported in the present study. Following parameters were collected at baseline (within the 2 weeks preceding implantation of the biventricular pacing system) and 6-month follow-up: history, physical examination, 12-lead electrocardiogram, 6-minute walk distance, cardiothoracic ratio, when feasible (some patients were in New York Heart Association class IV) peak VO2, echocardiographic parameters including end-systolic and end-diastolic diameters, fractional shortening, mitral regurgitation area, systolic pulmonary artery pressure, LV ejection fraction evaluated by radionuclide angiography. No significant change in pharmacological treatment occurred between inclusion and the 6-month visit.
Device implantation
The protocol of implantation used in our centre has been previously described [10,11]. Attempts were made to place the left ventricular lead in a lateral coronary vein where the most delayed local electrogram relative to the QRS onset was recorded. The electrical parameters (threshold, impedance) of the previously implanted right ventricular lead were verified after implantation of the LV lead. The LV lead was connected to the atrial port of the pacemaker, and the right ventricular lead to the ventricular port of a dual-chamber rate-responsive pacemaker. The AV delay (in this case LV–RV delay) was programmed at the shortest programmable value allowed by the device (30 ms). The pacemaker was then programmed in "DDIR" mode (rate-responsiveness programmed according to the status of each patient) and the accurate and permanent (>95% of the time) functioning of the device was carefully checked before discharge and at every follow-up visit.
End points and statistical analysis
Values are expressed as mean ± standard deviation. Statistical tests are intra-patient comparisons, values obtained in each individual at 6 months were related to those obtained in the same patient at baseline. Comparison of parameters between baseline and end of follow-up were performed using the Student's t test. Changes in these parameters were considered statistically significant when P value was <0.05.
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Results |
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Clinical characteristics
The LV lead was successfully implanted in the 16 patients with an acceptable acute pacing threshold (less than 3 V). During the study period two patients died from refractory heart failure associated with intestinal haemorrhage in one case. These two patients had similar baseline characteristics compared with patients who survived. Baseline characteristics of the 14 patients who completed the 6-month follow-up visit are listed in Table 1.
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Clinical outcome
At 6 months the 14 surviving patients showed significant (P=0.02) functional improvement: New York Heart Association class fell from 3.4±0.5 to 2.6±1.1 (Table 2). In spite of this marked improvement the 6-min walk distance remained unchanged (from 418±169 to 420±113 m, P=0.9). The peak VO2 calculated in 9 patients also remained unchanged at 14.1 l/min kg. QRS duration decreased from 192±28 to 177±23 ms, (P=0.12) and cardiothoracic ratio from 0.60±0.52 to 0.57±0.57 (P=0.04). The mean LV pacing threshold was 2.9±2.2 V and the mean impedance was 652±253
. No severe adverse events due to LV pacing were observed [12].
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Echocardiographic and angiographic parameters
Most of the echocardiographic parameters improved significantly at 6 months (Table 3): end-systolic diameter by 8% (P=0.01), fractional shortening by 24% (P=0.01), systolic pulmonary artery pressure by 17% (P<0.0001) and mitral regurgitation area by 40% (P<0.05). End-diastolic diameter decreased (4%) but the difference did not reach statistical significance (P=0.08). Ejection fraction measured by nuclear angiography increased by 17% (P=0.11).
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Discussion |
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The main result of the present study is that "upgrading" right ventricular apical pacing to biventricular pacing in patients with permanent atrial fibrillation and AV junctional ablation for rate control improves functional status and LV performance.
Why do patients with AV junctional ablation have CHF?
There are only speculative answers to this important question. It seems that patients could be divided into two subgroups. The first includes patients with persistent CHF in spite of ventricular rate control: it could be hypothesized that in this subgroup correction of tachycardia and irregularity of the ventricular rate is insufficient to reverse the effects of the underlying heart disease or that its beneficial effects are counterbalanced by the deleterious effects of right apical pacing [3–5,13,14]. In the second subgroup the "ablate and pace" procedure is successful in improving quality of life [1,2] and LV function [2]. However, in some patients after a few years of well-being, symptoms of cardiac failure appear or recur [15]. In this latter subgroup in addition to the natural evolution of the underlying heart disease, the deleterious effects of permanent right ventricular apical pacing have been incriminated. Although there are no hard data to support this hypothesis many points are in favour of this explanation [3–5,13]. Furthermore, the potential harmful effects of right ventricular apical pacing on LV function are certainly maximized in these pacemaker-dependent patients [14,16].
Why does resynchronization have beneficial effects?
As stressed by Leon et al. [17] patients with permanent atrial fibrillation and complete AV block after radiofrequency ablation of the AV junction provide an excellent model to evaluate the effects of different pacing sites on LV function. In that case influence of atrial transport is excluded due to atrial fibrillation and pacing is permanent as a consequence of complete AV block.
It is no longer a subject of debate that right ventricular pacing has deleterious effects on LV performance [13,18] but its mechanisms have not been extensively studied. Some authors have reported the occurrence of severe mitral regurgitation [13], others the induction of myocardial perfusion defects [3] but very few have assessed the consequences of right apical pacing on LV activation pattern [19]. It is generally considered that the pattern of LV activation is similar during right ventricular pacing to native left bundle branch block. Although it is probably not exactly the case [19] this assumption may be globally correct. Many studies have demonstrated by multigated equilibrium blood pool scintigraphy [20,21] or tissue Doppler imaging [22,23] that left bundle branch block induces major regional desynchronization of contraction in patients with cardiomyopathy and this may be reversed at least partially by CRT. In patients with long-standing right ventricular apical pacing the situation may not be completely comparable but it may be assumed that CRT has some similar effects and may reverse the abnormal contraction pattern with beneficial consequences on LV remodeling [22,23] without any increase in myocardial oxygen consumption [26]. Furthermore, it could be hypothesized that more coordinate LV contraction reduces mitral regurgitation as observed in the present study and in others [24,25,27,28].
Comparison with other studies
Cardiac resynchronization therapy has primarily been studied in patients in sinus rhythm but additional data have been reported in atrial fibrillation patients initially during acute haemodynamic studies [6] and recently during long-term pacing [9]. Patients included in these trials underwent AV junctional ablation to guarantee permanent ventricular pacing, setting the stage for effective resynchronization, thus the inclusion criteria were different from those in the present study. AV junctional ablation was a necessity to permit CRT in the first situation while in the second CRT was an adjunct to AV junctional ablation (delayed in some). The results obtained with CRT in atrial fibrillation patients were initially less encouraging than those observed in patients in sinus rhythm [8] but finally after a longer follow-up they appear equivalent [9]. In patients with AV junctional ablation for rate control of permanent atrial fibrillation who developed, secondarily, severe CHF initial results of CRT were based on encouraging case reports [26]. The first series has been published recently [17] and the results were in accordance with those reported in our study in terms of improvement in LV function evaluated mainly by echocardiography and in our study by cardiothoracic ratio and nuclear angiography. We also observed an improvement in quality of life based on the New York Heart Association class not associated with improvement in exercise test results, parameters which were not assessed in the study of Leon et al. [17].
Limitations
The main limitation of the study is the absence of a control group including patients randomly assigned to medical treatment. We felt, based on our preliminary experience [29], that this randomization would have not been ethical in these critically ill patients and furthermore the comparison would have required a much larger population of patients than a single centre could include. The results of our study, however, yield a strong argument in favour of designing a randomized trial if considered ethically acceptable.
Another limitation was that, given the open nature of the study, a placebo effect might have biased our results. We attempted to limit this by evaluating mostly objective parameters. Furthermore, follow-up was performed by physicians who were not directly involved in the analysis of the study data.
Conclusion
We conclude that CRT is an effective treatment to improve LV performance and functional status in patients with CHF and prior AV junctional ablation for ventricular rate control of permanent atrial fibrillation. However, the functional benefits are not observed during exercise testing suggesting either dissociated or undisclosed effects due to the limited number of patients or too short follow-up duration.
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