The European Society of Cardiology
Management of atrial fibrillation in cardiac resynchronization therapy
Clinical practice of CRT: how to improve the success rate
Department of Cardiology, German Heart Institute Berlin, Germany
Received 3 May 2004; accepted 24 May 2004.
* Christian Butter, Deutsches Herzzentrum Berlin, German Heart Institute Berlin, Kardiologie Augustenburger Platz 1, 13353 Berlin, Germany. Tel.: +49-30-4593-2400; fax: +49-30-4593-2500
butter{at}dhzb.de
Abstract
Background Mortality in severe congestive heart failure rises with the incidence of an inter- and intraventricular conduction delay and doubles if atrial fibrillation (AF) occurs. Electrical cardioversion (CV) is frequently regarded as less promising in these patients. Encouraged by first conversions during defibrillation threshold (DFT) testing we consecutively attempted electrical cardioversion in 30 patients selected for cardiac resynchronization therapy (CRT).
Methods After successful CV an additional atrial electrode was placed during implantation of a CRT device (ICD or pacemaker) to ensure AV sequential biventricular pacing. Regular clinical follow-up examinations up to 2 years were performed.
Results In 23 (75%) of 30 patients (onset of AF at least 6 months earlier), sinus rhythm (SR) could successfully be restored. Under antiarrhythmic medication in 21 patients SR was still present after 333±142 days. Furthermore, a significant increase of EF from 22% to 31% (
) with an accompanying significant increase of the VO2max from 12.9 to 16.1 ml/kg/min () was measured.
Conclusion In CRT candidates with supposed permanent AF more vigorous external or internal cardioversion attempts are justified. In the majority of patients SR can be established and persists for at least 1 year with a superproportional improvement in functional capacity.
Key Words: Atrial fibrillation • Cardioversion • Cardiac resynchronization therapy • Congestive heart failure • Left bundle branch block
Introduction
Atrial fibrillation is common in patients with heart failure; the prevalence is approximately 15–20% in these patients.1 The Framingham study showed that the relative risk for patients with pre-existing heart-failure to develop atrial fibrillation is 4.5 in men and 5.9 in women.2 People who developed atrial fibrillation had larger left atrial dimensions as well as larger left ventricular end-diastolic and end-systolic dimensions. The Framingham Heart Study demonstrated that atrial fibrillation is associated with an approximate doubling in mortality in subjects (male and female) with or without pre-existing cardiovascular disease.2
In the Italian Registry for congestive heart failure the importance of left bundle branch block (LBBB) and atrial fibrillation in heart failure patients became obvious. One-year mortality with atrial fibrillation and left bundle branch block was 26.5%, whereas it was 14.5% for heart failure patients with sinus rhythm and left bundle branch block, demonstrating a synergistic, unfavorable effect on prognosis.3
During early implantations of biventricular defibrillators in congestive heart failure patients with so-called permanent atrial fibrillation, we occasionally observed cardioversion into sinus rhythm during intraoperative defibrillation threshold testing by the internal shock delivered. Despite the fact that in this population with atrial enlargement, severely reduced left ventricular function and permanent atrial fibrillation (AF), electrical cardioversion (CV) is frequently regarded as less promising, we were encouraged by these initial observations and changed our clinical strategy from rate control to a more vigorous attempt to restore sinus rhythm, which allows the most physiological rate control and optimized left ventricular filling by AV-synchronous biventricular pacing. Functional improvements, such as increase of ejection fraction and peak oxygen consumption, after cardioversion have already been reported in non-CRT patients.4
This study presents the retrospective and prospective analysis of 23 patients who were supposed to be in permanent atrial fibrillation but were successfully cardioverted into sinus rhythm during the implantation of a biventricular device for resynchronization. They have been followed clinically up to more than 2 years.
Methods
Patient population and demographics
Out of 30 patients who were scheduled for resynchronization therapy at the German Heart Institute Berlin and presented with permanent atrial fibrillation, 23 were successfully cardioverted by either internal or external synchronous shock delivery.
Inclusion criteria were LV dysfunction with an ejection fraction 
35%, functional NYHA class III or IV and symptoms of chronic heart failure despite standard medical therapy. The baseline examination of these patients included history, study of previous ECGs to define the last documented sinus rhythm, physical examination, 12-lead ECG and evaluation of the functional status by echocardiography and CPX. Regular follow-up examinations including ECG, ECHO, CPX, IEGM analysis and data on the current medication were performed.
The mean age at inclusion was 63 years, except one all patients being male. The underlying disease was DCM in 18 cases and CAD in the rest. Eighteen patients received an ICD. Mean LVEDD was 73.6 mm, mean LVESD 64.3 mm and mean LA size 53 mm. Atrial fibrillation had existed for a mean time of nearly 22 months and the peak oxygen uptake was 12.3 ml/kg/min. Twenty-two patients received an ACE inhibitor, 19 a ß-blocking agent and four amiodarone (Tables 1 and 2).
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Device implantation
After the insertion of a venous and arterial access via the femoral vessels for hemodynamic monitoring and optimization, and fixation of epidermal patches for external cardioversion, a left-sided approach for subclavian vein puncture was predominantly chosen and three wires were transvenously inserted. After placement of the right ventricular lead apically the left ventricular lead was inserted via the coronary sinus at the free lateral wall of the left ventricle according to the venogram. After connection of these two leads to a temporary pacemaker an external synchronized shock (200J; 360J) was delivered under conscious sedation. In the case of restoration of sinus rhythm for at least a few beats the additional atrial lead was implanted. Finally, AV delay was invasively optimized according to pulse pressure and +dp/dt increase beginning with 60 ms up to the last capture at 20 ms AV steps.
Results
After cardioversion and implantation of a biventricular device patients were followed for a mean time of 333±142 days. Sixteen patients remained in stable sinus rhythm without further interventions; in seven atrial fibrillation reoccurred. This group is defined as having instable sinus rhythm in the following subanalysis. Five of these patients were successfully re-cardioverted (2 two times) and were in sinus rhythm during the final examination. Only in the remaining two patients did further attempts fail and rate control become the final treatment goal (Fig. 1).
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At the 10-month follow-up a significant improvement of VO2max of more than 4 ml/min/kg from 12.3 to 16.6 and a concomitant nearly significant increase of ejection fraction were demonstrated. Left ventricular end-diastolic and end-systolic diameter were reduced.
Whereas medication with ß-blockers and ACE inhibitors remained stable during the time course amiodarone had to be added in some patients to maintain sinus rhythm (Fig. 2).
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The degree of amiodarone medication is also the only difference distinguishing stable from instable patients during follow-up (Table 3 and Fig. 3). No other clinical parameters had an influence on the maintenance of sinus rhythm.
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) and unstable (
) patients. Due to the different group size differences do not reach statistical significance.These findings emphasize the importance of an adjunct antiarrhythmic therapy with amiodarone to stabilize physiological rhythm in heart failure patients treated with CRT.
Discussion
Risk of paroxysmal AF in CRT
Despite the development of new algorithms in CRT devices loss of sinus rhythm may result in a loss of resynchronization. In combination with the acute loss of physiological rate control, irregular left ventricular filling and sometimes fast ventricular response, in many patients rapid deterioration of functional capacity and left ventricular function is observed. In patients with an ICD back-up atrial fibrillation with a fast ventricular response may require a discharge despite the absence of ventricular arrhythmias because high heart rates are poorly tolerated in severely depressed left ventricular function.
Even an aggressive policy towards persistent atrial fibrillation by means of repetition of electrical cardioversion after early atrial fibrillation recurrence is useful in maintaining sinus rhythm. Therefore, recurring atrial fibrillation should not discourage the cardiologist from trying again.5
In our understanding the early detection of atrial arrhythmias by the patient or the physician should be one of the most important pieces of information transmitted by telephone, because this is the only chance to initiate an early intervention.
Strategies
There are different strategies to deal with so-called permanent atrial fibrillation. To restore physiological rate control and AV sequence, cardioversion is the best option. A study of hemodynamic changes4 showed an improvement in ejection fraction as well as increased peak oxygen consumption after cardioversion.
In patients with recurrent atrial fibrillation ventricular rate control is of importance to avoid further deterioration of left ventricular function.
Etienne et al.6 showed that both biventricular and left ventricular pacing in patients with congestive heart failure significantly improved acute hemodynamic findings to a similar degree in patient groups with sinus rhythm and atrial fibrillation, suggesting that left ventricular based pacing may be beneficial in patients with severe cardiac failure regardless of whether or not they are in sinus rhythm.
The MUSTIC study7 demonstrates a beneficial effect of biventricular pacing in patients with CHF who are in sinus rhythm as well as for those with atrial fibrillation. In the sinus rhythm group 6-min walking distance increased by 23% during biventricular pacing, the quality-of-life score improved, peak oxygen uptake increased, and hospitalizations were reduced by two-thirds. Active pacing was preferred by 85% of the patients. These results were confirmed in the 12-month follow-up. The results for patients with atrial fibrillation were less impressive; nevertheless, in this group there was also an improvement in the 6-min walk test, in NYHA group, in peak oxygen uptake and in left ventricular ejection fraction as well as a decrease in the number of hospitalizations. For further benefit, cardioversion of this subgroup of patients should be considered.
If the ventricular rate is refractory to pharmacological control in patients who did not stay in stable sinus rhythm after cardioversion, atrioventricular nodal ablation and pacemaker implantation are an alternative. This strategy has been shown to improve left ventricular ejection fraction in some studies in patients with or without heart failure as the underlying disease.8,9
Studies comparing the effects of restored sinus rhythm to rate control have mainly targeted neither a heart failure population nor patients with conductance disorders such as left bundle branch block. For instance the AFFIRM study10 showed that the rhythm control had no survival advantage over the rate control approach in a large population of patients. A total of 194 of these patients had cardiomyopathy, but no subgroup analysis was performed; thus this study gives no insight into the advantages or disadvantages of rhythm control in this subgroup. Also in the smaller RACE study11 no significant differences for prevention of death and morbidity between the rate control and the rhythm control group could be seen. In this study, 11 patients with cardiomyopathy were included, but here also no subgroup analysis was performed.
These data promote a rate control approach as the initial strategy for the vast majority of patients with persistent atrial fibrillation. For the minority who remain highly symptomatic aggressive rhythm control with consideration of invasive treatments, such as pulmonary vein ablation or improved rate control with atrioventricular nodal ablation and back-up ventricular pacing, should be considered.
Whether these strategies can be transferred to patients with severe congestive heart failure and left bundle branch block remains completely unknown at the moment. Data from the Italian heart failure registry clearly demonstrate that LBBB and AF are both associated with a significantly increased mortality and their association has a synergistic, unfavorable effect on prognosis. This cumulative effect is still evident after adjusting for clinical factors. These data support the hypothesis that ventricular resynchronization as well as restoration of sinus rhythm could improve the prognosis of CHF.10,11 Only studies with small patient populations have so far given an insight into the effect of restoring sinus rhythm in patients with congestive heart failure. Based on the simple parameters fractional shortening and NYHA class, Azpitarte et al.12 showed that patients benefit from cardioversion even if they have had adequate heart rate control before. The patients who could be cardioverted and sustained long term sinus rhythm had an increased fractional shortening from a mean of 20% before cardioversion to a mean of 31% 6 months after cardioversion. No significant changes in left ventricular fractional shortening could be seen in those patients who had recurrent atrial fibrillation sinus rhythm. Also, an improvement in NYHA class was observed in those patients who had sustained sinus rhythm.
Even though these studies are small and not controlled and their conclusions have to be interpreted with caution, they may provide some clinical support of experimental data which have already proven a better emptying of the LA at LV end-diastole, and thus removal of the restraining pericardial force, a downward shift in the end-diastolic pressure–diameter relationship and an improvement (upward shift) of the ventricular functioncurve after restoration of sinus rhythm. These favorable hemodynamic changes may account for the reported long-term stability of sinus rhythm and the improvement in exercise performance after successful cardioversion in our patients.13–15
Clinical implications
Based on these studies and our observations the following clinical strategies may be suggested. Patients with congestive heart failure who also suffer from atrial fibrillation should be examined by echocardiography to consider whether they might benefit from a resynchronization strategy. If so, cardioversion should be considered and achieving stable sinus rhythm should be the primary goal. Prior to cardioversion a left atrial thrombus has to be excluded and intravenous anticoagulation has to be initiated. Cardioversion can be attempted prior to or during the implantation of a CRT device while the intraoperative approach seems preferable, allowing temporary back-up pacing in depressed sinus node function and prolonged intrinsic AV conductance.
If the intraoperative cardioversion succeeds, an additional atrial lead has to be implanted. With permanent pacing capabilities antiarrhythmic medication can be initiated or optimized by adding or titrating ß-blocking agents and amiodarone. Even in cases of unsuccessful cardioversion attempts the implantation of an atrial lead might be considered in general because spontaneous conversions after longer periods of resynchronization have been reported,16 probably caused by reversed remodeling. Early repeated follow-up examinations are necessary for all of these patients to check for the underlying rhythm. The unrecognized onset of atrial fibrillation still has to be considered a critical hemodynamic event. Despite new algorithms implemented in CRT-devices to maintain biventricular pacing during the onset of atrial fibrillation, rapid progression of congestive heart failure usually occurs.
As soon as recurrent atrial fibrillation is noticed, immediate further internal or external cardioversions have to be initiated restoring the AV-sequential biventricular pacing mode.
Under an optimized and titrated medical therapy with ß-blocking agents and amiodarone the need for AV-node ablation or modulation is limited and is the exception. Nevertheless, permanent oral anticoagulation has to be recommended in all these patients to prevent embolic events in case of recurrent atrial fibrillation.
Conclusion
Our data demonstrate that in a patient population with severely depressed left ventricular function, left bundle branch block and permanent atrial fibrillation a more vigorous approach to restoring sinus rhythm is justified prior to implantation of a CRT device. Even of patients who are generally not considered for cardioversion attempts, 75% were successfully treated with internal or external synchronized shock. Supported by an optimized concomitant antiarrhythmic drug therapy with ß-blockers and amiodarone and repeated cardioversions, more than 90% of these were in sinus rhythm after 1 year and benefit from AV-sequential biventricular stimulation. Despite the small number of patients and the lack of a control group the functional improvement seems to be more impressive than in previously published studies with CRT and accepted atrial fibrillation. This may be due to the extensive invasive hemodynamic AV-delay optimization in each individual patient. We believe that, based on our observational data physicians, may be encouraged to be more optimistic about cardioversion in heart failure patients with LBBB and atrial fibrillation.
Whether the restoration of sinus rhythm compared to permanent atrial fibrillation can reduce mortality in CRT patients remains unclear at the moment, but should be the target of future randomized trials with a larger number of patients.
References
- Carson PE, Johnson GR, Dunkman WB et al. for the V-heFT VA Cooperative Studies Group. The influence of atrial fibrillation on prognosis in mild to moderate heart failure: the V-HeFT studies. Circulation 1993;87(Suppl VI):VI-102–10
- Benjamin EJ, Wolf PH, D'Agostino RB. Impact of atrial fibrillation on the risk of death. The Framingham heart study. Circulation. 1998;98:946–952
[Abstract/Free Full Text] - Baldasseroni S, Opasich C, Lucci D, et al. Cumulative effect of combined complete left bundle-branch block (LBBB) and atrial fibrillation (AF) on 1-year mortality in patients with congestive heart failure (CHF): data from IN-CHF registry. Eur. J. Heart Fail. 2001;3(Suppl 1):
- Van Gelder IC, Crijns HJ, Blanksma PK, et al. Time course of hemodynamic changes and improvement of exercise tolerance after cardioversion of chronic atrial fibrillation unassociated with cardiac valve disease. Am. J. Cardiol. 1993;72(7):560–566[CrossRef][Web of Science][Medline]
- Bertaglia E, D'Este D, Zerbo F, et al. Success of serial external electrical cardioversion of persistent atrial fibrillation in maintaining sinus rhythm. A randomized study. Eur. Heart J. 2002;23:1522–1528
[Abstract/Free Full Text] - Etienne Y, Mansourati J, Touiza A, et al. Evaluation of left ventricular function and mitral regurgitation during left ventricular-based pacing in patients with heart failure. Eur. J. Heart Fail. 2001;3:441–447[CrossRef][Web of Science][Medline]
- Cazeau S, Leclercq C, Lavengne T. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N. Engl. J. Med. 2001;344:873–900
[Abstract/Free Full Text] - Brignole M, Gianfranchi L, Menozzi C, et al. Assessment of atrioventricular junction ablation and DDDR mode-switching pacemaker versus pharmacological treatment in patients with severely symptomatic paroxysmal atrial fibrillation. Circulation. 1997;96:2617–2624
[Abstract/Free Full Text] - Wood MA, Brown-Mahoney C, Kay GN, et al. Clinical outcomes after ablation and pacing therapy for atrial fibrillation: a meta-analysis. Circulation. 2000;101:1138–1144
[Abstract/Free Full Text] - AFFIRM Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825–33
- Van Gelder IC, Hagens VE, Bosker HA, et al. Rate control versus electrical cardioversion for persistent atrial fibrillation (RACE) Study Group. N. Engl. J. Med. 2002;347:1834–1840
[Abstract/Free Full Text] - Azpitarte J, Baun O, Moreno E, et al. In patients with chronic atrial fibrillation and left ventricular systolic dysfunction, restoration of sinus rhythm confers substantial benefit. Chest. 2001;120(1):132–138
[Abstract/Free Full Text] - Xiong C, et al. Atrial and ventricular function after cardioversion of atrial fibrillation. Br. Heart J. 1995;74:254–260
[Abstract/Free Full Text] - Lipkin, et al. Delayed improvement in exercise capacity after cardioversion of atrial fibrillation to SR. Br. Heart J. 1988;59:572–577
[Abstract/Free Full Text] - Ueshima K, et al. The effect of cardioversion on exercise capacity in patients with atrial fibrillation. Am. Heart J. 1993;126:1021–1024[CrossRef][Web of Science][Medline]
- Malinowski K. Spontaneous conversion of permanent atrial fibrillation into stable sinus rhythm after 17 months of biventricular pacing. Pacing Clin. Electrophysiol. 2003;26(7 Pt 1):1554–1555[CrossRef][Medline]
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