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European Journal of Echocardiography 2005 6(5):344-350; doi:10.1016/j.euje.2004.12.001
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Copyright © 2005, The European Society of Cardiology

The presence of contractile reserve has no predictive value for the evolution of left ventricular function following atrio-ventricular node ablation in patients with permanent atrial fibrillation

Tamas Szili-Torok*, Manos Bountioukos, Agnes J.Q.M. Muskens, Dominic A.M.J. Theuns, Don Poldermans, Jos R.T.C. Roelandt and Luc J. Jordaens

Department of Cardiology, Thoraxcentre, Erasmus MC, Rotterdam, The Netherlands

Received 3 April 2004; .

szilitorok{at}chello.hu

* Corresponding author. Department of Clinical Electrophysiology, Thoraxcentre, Rotterdam, Dr Molewaterplein 40, 3015 GM, Rotterdam, The Netherlands. Tel.: +31 10 4633991; fax: +31 10 4634420.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Aims

Transcatheter ablation of the atrio-ventricular (AV) node followed by ventricular pacing has been shown to improve symptoms and quality of life (QOL) of patients with permanent atrial fibrillation (AF). In a considerable number of patients, cardiac function deteriorates after AV node ablation. We aimed to determine whether the absence of contractile reserve assessed by low dose dobutamine stress echocardiography (LDDSE) could identify those patients whose left ventricular (LV) function deteriorates after AV node ablation.

Methods

All 25 patients studied had permanent AF for at least 12 months. LVEF was determined 6 days and 3 months after AV node ablation by radionuclide ventriculography (RNV), at a paced rate of 80beats/min. Deterioration in cardiac function was defined as a decrease in LVEF >5%. LDSE was performed in all patients before and after ablation. The presence of contractile reserve was defined as an improvement in regional function of ≥1 grade at low dose dobutamine in at least 4 segments. QOL measurements were taken using Minnesota, NHBP and MPWB questionnaires.

Results

LVEF showed no improvement in the overall group (52.8±11.1% vs. 51.8±9.8%, p=NS). QOL showed significant improvement in all questionnaires (Minnesota: 4.1±2.1 vs. 2.5±2, p=0.001; NHBP: 54.8±43.3 vs. 34.2±34.3, p=0.002; MPWB: 22.2±4.6 vs. 19.4±6.2, p=0.03). There was no significant difference in change of LVEF between patients with and without contractile reserve (–0.4±8.7 vs. 1.6±11.3, p=NS). However, patients with a preserved LVEF at baseline showed more frequently a reduced LVEF after AV node ablation (62.2±10.4% vs. 47.5±7.6%, p=0.001).

Conclusions

(1) The absence of contractile reserve does not predict deterioration of cardiac function after AV node ablation. (2) AV node ablation results in a significant improvement in QOL, which is not necessarily associated with improvement of LVEF. (3) Higher baseline LVEF predicts deterioration of cardiac function. These data suggest that although AV node ablation is an excellent way of controlling symptoms, it should be avoided in patients with normal LV function.

Keywords: Atrial fibrillation; AV node ablation; Cardiac function; Contractile reserve


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Atrial fibrillation (AF) is a common supraventricular arrhythmia, which leads to cardiac dilatation and dysfunction. Theoretically, ablation of the atrio-ventricular (AV) node followed by right ventricular (RV) apical pacing may result in an improvement of the patient's symptoms as well as in cardiac function because of the advantage of a regular ventricular response and adequate rate control.1–4 Controversial results were reported about the course of patients following AV junction ablation. Quality of life (QOL) and exercise tolerance improved in several studies.3 However, more recent studies indicate that left ventricular (LV) function does not improve or even may deteriorate.5–7 Contractile reserve of the myocardium as determined with echocardiography under pharmacological stress, can be used as a prognostic parameter in patients with LV dysfunction.8 The aim of the present investigation was to determine whether the absence of contractile reserve assessed by low dose dobutamine stress echocardiography (LDDSE) could identify those patients whose LV function deteriorates after AV node ablation and RV apical pacing.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Patients were eligible if they had permanent AF, were highly symptomatic and if the ventricular rate could not be adequately controlled by drug therapy. Twenty-five patients with permanent AF underwent ablation of the AV node and insertion of a VVIR pacemaker and RV apical pacing. There were 16 men and 9 women with an age ranging from 44 to 80 years (63±11.4, mean±SD) at the time of ablation. There were no major changes in medication during the 3-month follow-up period.

Study protocol
After being informed all patients gave consent for participation in the study. All patients who met the inclusion criteria had LDDSE, cardiac peptide measurements, QOL measurements and 6-min walk test before the procedure. Left ventricular ejection fraction (LVEF) was determined with radionuclide technique, 4–6 days after AV node ablation and PM implantation. At 3-month follow-up all measurements (LDDSE, QOL, cardiac peptides, 6-min walk test and LVEF) were repeated.

Ablation procedure
A temporary pacing electrode was inserted via a femoral vein into the RV before the ablation procedure. One patient had already a permanent pacemaker inserted. Third degree AV block was achieved using a conventional right-sided approach. A permanent cardiac pacemaker was inserted 30min after successful ablation. Neither major nor minor complications related to ablation and pacemaker insertion was observed. Patients were subsequently controlled at the outpatient clinic. For 15 patients either a Vitatron Clarity or St Jude Affinity pulse generator was implanted. The remaining 10 patients had a previously implanted VVIR or DDDR pacemaker. After ablation the pacemaker was programmed to 80bpm VVI mode. Permanent programming was performed after the second set of measurements was completed.

Echocardiographic measurements
M-mode and cross-sectional echocardiograms were obtained at the time of measurement of LVEF by radionuclide ventriculography. Left atrial (LA) size, left ventricular end-systolic (LVESD) and end-diastolic diameters (LVEDD) were measured according to the recommendations of the American Society of Echocardiography.

Dobutamine stress echocardiography
Two-dimensional images were acquired from three apical views (4 chamber, 2 chamber and long axis) and one parasternal view (short axis). After the acquisition of rest images, dobutamine was infused at a starting dose of 5µg/kg/min for 5min, followed by 10µg/kg/min for 5min (low dose stage). Dobutamine was then increased by 10µg/kg/min every 3min to a maximum dose of 40µg/kg/min. Atropine (up to 2mg) was added at the end of the last stage if the target heart rate had not been achieved. The baseline, low dose, peak stress and recovery images were displayed as a cineloop format. A 16-segment model for left ventricular wall function analysis was used, as recommended by the American Society of Echocardiography, and visually scored by 2 experienced reviewers. Each segment was scored as follows: 1=normal; 2=mildly hypokinetic; 3=severely hypokinetic; 4=akinetic; 5=dyskinetic. For each patient, wall motion score (WMS) was calculated at rest, at low dose dobutamine infusion and at peak heart rate. Reduction of wall thickening and new wall motion abnormalities during the stress test were considered to be hallmarks of ischemia. The transition of akinesia to dyskinesia was considered a mechanically induced phenomenon. The presence of contractile reserve was defined as an improvement in regional function of ≥1 grade at low dose dobutamine in at least 4 segments. Patients with ischemia were excluded from further analysis.

Evaluation of other parameters
LVEF was measured with radionuclide ventriculography (red blood cells, marked with Technetium99 pertechnetate, 25mCi). Imaging was performed in 45 degrees left anterior oblique (LAO) view. The R wave was used for gating, and 16–24 frames per cycle were stored until 400 000 counts per image were acquired. Measurement was made 4–6 days and 3 months after the ablation procedure. For all patients VVI 80bpm pacing mode was temporarily programmed 1h before LVEF measurements. Deterioration in cardiac function was defined as a decrease in LVEF >5%.

Cardiac peptide measurements
Before stress echocardiography a blood sample was drawn from a peripheral vein, after the patient had rested for at least 30min in a supine position. Plasma concentrations of ANP, BNP levels were measured with radio-immunoassays using standard commercial kits (Shionoria ANP and BNP kits, Shionogi, Osaka, Japan). The 6-min walk was done according to the established methods.9

Quality of life (QOL) was measured using the Dutch version of Minnesota living with heart failure, the Dutch version of Nottingham Health Profile, and the MPWB questionnaires.10,11

Statistical analysis
The measured values are expressed as mean±SD. Data showing Gaussian distribution were compared using paired (data before and after ablation) and student's t-tests (comparing data in the subgroups). Dichotomous variables were compared using chi-square test. Non-parametric data were compared using Wilcoxon test. The level of significance was set at 0.05.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Patient data
Complete heart block was achieved in all patients, except in one, who was rescheduled and only included for follow-up after a successful redo procedure (Table 1). Junctional escape rhythm was achieved in 18 patients (72%). The remaining patients had a ventricular escape rhythm. There were no complications related to the ablation and pacing procedures. The patient population was a mixed group of patients with permanent atrial fibrillation, 10 patients had an LVEF lower than 50% (ranging 35–74%). Walk test for 6-min was ranging from 193m to 545m.


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  		Table 1 Clinical characteristics and ablation data of the study patients

 
Evolution of objective and subjective parameters during the follow-up period
None of the measured objective parameters showed improvement during the follow-up period. QOL showed highly significant improvement in all the questionnaires (Table 2). The distribution of deteriorators and stable/improving patients were statistically not significant in subgroups of patients with or without contractile reserve (Table 3). A total number of 8 patients (32%) showed deterioration of LVEF >5% in the whole study population.


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  		Table 2 Evolution of objective and subjective parameters following AV node ablation in the overall group

 


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  		Table 3 Frequency of deteriorators and stable/improving patients in the groups with and without contractile reserve

 
Correlation of contractile reserve and changes over time
There was no significant difference in change of LVEF between patients with and without contractile reserve (–0.4±8.7 vs. 1.6±11.3, p=NS) (Table 4). However, patients with a preserved LVEF at baseline showed more frequently a reduced LVEF after AV node ablation (62.2±10.4% vs. 47.5±7.6%, p=0.001). There was no other statistically significant difference in baseline values including cardiac peptide serum levels, 6-min walk distances and WMS and QOL scores.


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  		Table 4 Comparison of baseline objective and subjective parameters following AV node ablation between stable or improvers and deteriorators

 
Evolution of subjective and objective parameters in subgroups of patients
In both the subgroups QOL showed improvement (Table 5). Apart from LVEF (which served as a grouping value in this comparison) no objective parameters showed change during the 3-month follow-up. LVEF decreased from 62.2±10.4 to 51.4±13% in the deteriorating group. LVEF showed substantial improvement in the improving group from 47.5±7.6 to 52±8.1%.


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  		Table 5 Evolution of objective and subjective parameters following AV node ablation in subgroups defined as stable or improvers and deteriorators

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Effect of AV node ablation and RV apical pacing on the function of the heart
Diminished LV function during pacing at the RV apex has been known for decades from numerous animal and human studies.12–14 Ventricular pacing results in an abnormal sequence of activation, associated with decreased fiber shortening, contractile work, and myocardial blood flow and oxygen consumption in regions activated early and increases in these parameters in those regions with delayed activation leading to a depressed left ventricular function.15–17 Experimental animal data have also indicated that RV apical pacing may decrease regional myocardial blood flow within the interventricular septum.18,19 These animal data have been confirmed by human studies, where ventricular pacing decreased resting coronary flow velocity in some patients.20 Furthermore, long term RV apical pacing results in a high incidence of myocardial perfusion defects associated with apical wall motion abnormalities and impaired global LV function.21 According to these data, abnormal activation of the ventricles by RV apical pacing may result in multiple abnormalities of cardiac function, which may ultimately affect clinical outcome. On the other hand, reports were showing improvement of LV function after AV node ablation and pacing. These are the patients most likely having a tachycardiomyopathy.1,2 Unfortunately, there was no available method, which was able to predict which particular patient will improve function after ablation. This can be recognised examining the course of patients with AV node ablation and RV apical pacing. Clinically it is seen, and also shown by most studies that a relatively large proportion of the patients is deteriorating while others are improving.2,6,7 To the best of our knowledge this is the first study aiming to determine which patient will deteriorate and who will improve after such a therapy. This question becomes even more important after consideration of the QOL data. Because there is a uniform improvement in QOL it seems to be important to recognise patients with a potential deterioration of cardiac function.

Rationale for measuring contractile reserve in patients undergoing AV node ablation and permanent RV pacing
After AV node ablation the chronotropic response of the sinus node is lost and hemodynamic adaptation will be more dependent on changes in contractility than by changes in the heart rate. Patients with tachycardiomyopathy usually suffer from long lasting fast heart rates and their LV function will likely improve after such intervention.1,22,23 It has been shown that in patients with idiopathic dilated cardiomyopathy and long lasting atrial fibrillation (having normal coronary arteries) the LVEF does not improve with low dose dobutamine. However, patients with a tachycardiomyopathy do improve.8 This can be the rationale for using LDDSE as a screening test before patients undergo AV node ablation and pacing. Our data did not confirm that it would be useful for these patients. There was significant difference between the duration of AF between our study patients and the previous study when LDDSE was predictive for improvement. The latter patients had persistent AF, while our patients had permanent long lasting AF regardless their LV ejection function. The fact that almost all patients had symptomatic improvement in our study can be explained by the fact, that circulating cathecolamines can no longer accelerate the heart rate, but will only affect the pump function. This will not necessarily improve the outcome of the patients with contractile reserve, but will definitely not influence the ones without contractile reserve.

Left ventricular function after AV node ablation and RV apical pacing for patients with permanent AF: discordant evolution of subjective and objective parameters
Our data confirm that the functional course of patients following AV junction ablation is unpredictable. Although noticeable improvement in QOL associated with improved LVEF has been reported in many studies, some other studies reported no improvement or sometimes a decreased LV function.1–3,6,7,22–24 An important aspect of these controversial data is that in most available large studies only data in the overall group were reported, despite the obvious fact that some patients deteriorated. Correct interpretation of these data may allow us to develop a better understanding of the natural course of these patients and the reasons for this discordance. After AV node ablation numerous factors are influencing LV function. Some of them act in the direction of improvement, but some of them may cause deterioration. Regularisation and ventricular rate control appear to be the most important factors that may have an impact on the improvement.4 On the other hand RV apical pacing results in disadvantageous cellular changes and worsened hemodynamics.5,7,13,16,25,26 It seems so far, that the net effect of interplay between the beneficial and the worsening factors is unpredictable. The almost uniform improvement in quality of life supports the idea that subjective parameters are more influenced by the beneficial factors, however, function reacts independently. In some patients, concordant with the QOL, function improves, however in others, despite the improvement in QOL, it may deteriorate. Therefore, in symptom control, regularisation and rate control are important factors, but their role in functional changes is not that clear. This variable outcome is of clinical significance as per the important question of Wood, as to whether AV node ablation is applicable to a wider spectrum of patients.2 According to our present data we can conclude that the effect of AV node ablation and RV apical pacing on cardiac function is highly dependent on the baseline LVEF. It seems that patients with preserved LV function will more likely deteriorate their LV function. Therefore, this therapy should be avoided in patients when only symptom control is the goal and when the cardiac function is normal. This is in concordance with the concept of tachycardiomyopathy. It seems, that AV node ablation and RV apical pacing is the best for patients with tachycardiomyopathy. However, this cannot be predicted with the presence of contractile reserve in these patients.

Limitations of the study
After AV node ablation drugs used for ventricular rate control are usually withdrawn from the patients. Since most of these drugs are having negative inotropic effect their influence on the evolution of LVEF cannot be excluded. Furthermore, the withdrawal of these pharmacological agents could improve quality of life, therefore might be responsible for the detected discordant evolution. Another issue is that right ventricular pacing results in an asynchronous activation of the ventricles and might influence WMS measurements.

In conclusion, in this study subjective and objective parameters as obtained at short and midterm after AV node ablation showed discordant evolution. Subjective parameters measurement by QOL questionnaires is markedly improving in most patients but parameters associated with LV performance are not improving and in a significant subset of patients these latter parameters even display deterioration. A good baseline LVEF is the best predictor of deterioration.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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