TY - JOUR
AU - Pehrson,, Steen
AB - Abstract The mainstay of treatment for atrial fibrillation, AF, remains pharmacologic control, either by maintaining sinus rhythm or by controlling the ventricular rate and allowing AF to continue. In patients where pharmacologic therapy i not effective, not tolerated or contraindicated, nonpharmacologic treatment may be beneficial. In the last two decades the number of nonpharmacologic treatment options (catheter ablation, cardiac pacing, internal defibrillation, and dysrhythmia surgery) for AF have markedly increased and the number of patients undergoing such treatment is steadily increasing. The most important reason for these treatment strategies is the hope of reducing symptoms, preventing complications and improving quality of life, QoL. However, the impact of nonpharmacologic therapy on QoL is far from established. Following a short presentation of the basic definitions and instruments used in QoL research the present paper reviews clinical studies that have assessed QoL in patients undergoing nonpharmacologic treatment of AF. Major limitations and methodological problems are emphasized. Among these are highly selected often-heterogenous patients groups, small size, lack of control group and the use of non-validated QoL instruments. Furthermore, in most studies antiarrhythmic medication have been discontinued at the time of the intervention and it is not clear to which degree the improvement in QoL is related solely to the nonpharmacologic treatment or to the removal of drug related adverse effects. Although the currently available data from adequately designed studies are sparse and further investigations are needed, it is noteworthy that the majority of patients undergoing nonpharmacologic treatment report enhanced QoL. Atrial fibrillation, Quality of life, Nonpharmacologic therapy, Maze procedure, Cardiac pacing, Catheter ablation 1 Introduction Atrial fibrillation, AF, is the most common clinically significant cardiac rhythm disturbance and is associated with substantial complications and health care costs. The prevalence of AF is increasing with age and the reported prevalence of AF ranges from less than 0.5% in people 25 to 35 years of age, to 1.5% of people up to 60 years of age, to 9% in people older than 75 years of age.1Furthermore reports from western populations concurrently indicate a significant increase in hospital incidence of AF2,3often described as ‘the epidemic of AF’. An epidemic, which to some extent may be explained by the combination of improved diagnosis of the arrhythmia, increased awareness among referring physicians and increased longevity in the industrial societies. In contrast to life-threatening arrhythmias, AF may appear benign but may reveal its detrimental effects only after many years. In the Framingham Study AF patients had a nearly two-fold increase in all-cause mortality and a four- to five-fold risk for a stroke.4The management of AF is complex and richly faceted with anticoagulation therapy in combination with antiarrhythmic drugs as the first-line treatment strategy5and with the nonpharmacologic therapies (catheter ablation, cardiac pacing, internal defibrillation, and antiarrhytmic surgery) playing an increasingly important role.1,6As the impact of these varying therapies on morbidity and mortality is unclear, the reduction in symptoms and an improvement in quality of life, QoL, are the most important reasons for treating patients with idiopathic or hypertension related AF.7QoL have gradually been acknowledged as equally important as traditional measures of disease burden and since the early 70s there have been a nearly exponential increase in the use of quality of life end points in clinical research. Cardiovascular research is very well represented in the field of reporting quality of life coming just second to cancer research. A search of the Cochrane Controlled Trials Register showed that in studies reporting on quality of life the most commonly conditions were cancer (29%) and cardiovascular disease (26%) with other research domains occurring in less than 10% of studies.8 In the last two decades the number of nonpharmacologic treatment options for AF has markedly increased, see Table 1. These new techniques have expanded the indications for nonpharmacologic treatment and the number of patients undergoing such treatment is steadily increasing. Despite the growing popularity of nonpharmacologic strategies their impact on QoL have not been evaluated widely. The first part of this review is an introduction of basic definitions and instruments used in QoL research. The second part of this article reviews published clinical studies that have assessed QoL in patients undergoing nonpharmacologic treatment of AF. Finally the third part sum up the methodological problems involved in the assessment of QoL in nonpharmacologic treatment of AF and proposes a set of eight criteria to be fulfilled when planning QoL studies in the future. Table 1 Nonpharmacologic treatment options for atrial fibrillation Procedure . . Surgical Maze operation AV node ablationa Left atrial isolationa Corridor procedure Catheter-based AV node ablation AV node modification Linear ablation (‘Catheter maze’)b Focal ablationb Pacemaker implantation Atrial based pacing (DDD, AAI) Biatrial pacing (RAA+CS) Dual-site right atrial pacing Implantable atrial defibrillator Procedure . . Surgical Maze operation AV node ablationa Left atrial isolationa Corridor procedure Catheter-based AV node ablation AV node modification Linear ablation (‘Catheter maze’)b Focal ablationb Pacemaker implantation Atrial based pacing (DDD, AAI) Biatrial pacing (RAA+CS) Dual-site right atrial pacing Implantable atrial defibrillator a Not currently used. b Linear ablation may be combined with focal ablation. DDD, dual chamber pacing; AAI, atrial demand pacing; RAA, right atrial appendage; CS, coronary sinus. Open in new tab Table 1 Nonpharmacologic treatment options for atrial fibrillation Procedure . . Surgical Maze operation AV node ablationa Left atrial isolationa Corridor procedure Catheter-based AV node ablation AV node modification Linear ablation (‘Catheter maze’)b Focal ablationb Pacemaker implantation Atrial based pacing (DDD, AAI) Biatrial pacing (RAA+CS) Dual-site right atrial pacing Implantable atrial defibrillator Procedure . . Surgical Maze operation AV node ablationa Left atrial isolationa Corridor procedure Catheter-based AV node ablation AV node modification Linear ablation (‘Catheter maze’)b Focal ablationb Pacemaker implantation Atrial based pacing (DDD, AAI) Biatrial pacing (RAA+CS) Dual-site right atrial pacing Implantable atrial defibrillator a Not currently used. b Linear ablation may be combined with focal ablation. DDD, dual chamber pacing; AAI, atrial demand pacing; RAA, right atrial appendage; CS, coronary sinus. Open in new tab 2 Definitions and descriptions of QOL The evaluation of QoL is inherently subjective and no consensus on the definition exists. Most approaches used in medical contexts do not attempt to include more general notions such as life satisfaction or living standards9and tend rather to concentrate on a multidimensional construct based on four components: physical condition, psychological well-being, social activities and everyday activities. The lack of a clear definition of QoL is reflected in the many instruments that have been proposed to measure it.8Indeed, a state of the art review identified some 150 different measures.10However, there are two basic approaches to measure QoL: generic instruments and disease specific instruments. Generic instruments are used in the general population to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. They are usually not specific to any particular disease state or susceptible population of patients and are therefore most useful in conducting general survey research on health and making comparisons between disease states.11The generic instruments facilitate comparisons among different disease groups, however, the broad approach may reduce responsiveness to effects of health care. Currently The Medical Outcome Study Short-Form Health Survey, SF-36,12is the most widely validated generic instrument available. Disease-specific instruments focus on the domains most relevant to the disease or condition under study and on the characteristics of patients in whom the condition is most prevalent. Disease-specific instruments are most appropriate for clinical trials in which specific therapeutic interventions are being evaluated. Disease-specific instruments have several theoretical advantages. They reduce patient burden and increase acceptability by including only relevant dimensions. Disadvantages are the lack of comparability of results with those from other disease groups and the possibility of missing effects in dimensions that are not included.13The Symptom Checklist: Frequency and Severity14and The Modified Karolinska Questionnaire,KQ,15are both well-validated representatives of cardiac specific questionnaires. Apart from being generic or disease-specific the instrument should possess several important psychometric properties, which includes coverage, reliability, validity, responsiveness, sensitivity, and practicality, see text . Textbox 1 Basic requirements of quality of lifeassessments multidimensional construct: the instrument reflects several dimensions of QoL. coverage: the measurement of QoL should address each objective and subjective component (symptom, condition, or social role) that is important to members of the patient population and is susceptible to being affected, positively or negatively, by interventions. reliability: this concerns wether the measure produce the same results when repeated in the same population under the same conditions. validity: concerns wether the instrument measures what it is intended to measure, such as QoL. responsiveness: this is a measure of the association between the change in the observed score and the true value of the construct.11 sensitivity: refers to the ability of a measurement to reflect true changes or differences in QoL.12 practicality: for a measure to be useful in clinical practice it must not only be valid, appropriate, reliable, responsive and sensitive, but it must be simple, quick to complete, easy to score and provide useful clinical data.16 3 Studies of quality of life in nonpharmacologic treatment of atrial fibrillation The mainstay of treatment for AF remains pharmacologic control, either by maintaining sinus rhythm or by controlling the ventricular rate and allowing AF to continue. However, both strategies have several limitations. Drug therapy to suppress atrial fibrillation and maintain sinus rhythm is often ineffective with a recurrence rate to AF in approximately 50% at 6 months during therapy with the best available drugs.6Furthermore, both regimes are frequently poorly tolerated because of adverse effects and interactions with other drugs. A third limitation of pharmacologic therapy is the risk to the patient from the prescribed therapy. Indeed data are accumulating on increased mortality in patients receiving antiarrhythmic drug therapy.17–19It is for the portion of patients who either remains symptomatic while receiving pharmacologic therapy or who experience adverse drug effects that nonpharmacologic options until now have beenoffered. 4 Surgical therapy Operative treatment for the patient with refractory AF has been available since early 1980s. The Maze operation, designed by James L. Cox and co-workers, is clearly successful at restoring sinus rhythm, AV synchrony and atrial systole, and thereby diminish the risk of thromboembolism.20It is an open-heart operation requiring cardiopulmonary bypass, and until now, usually reserved as a therapy of last resort for patients undergoing another clinically indicated surgical procedure, such as mitral valve repair or replacement. However, in a longitudinal study by Lönnerholmet al.21the indications for the Maze procedure were expanded to a group of patients with mostly (80%) lone AF, were AF was the primary indication for surgery in all patients. QoL was the primary endpoint in this study and was assessed before operation as well as 6 and 12 months after surgery using the SF-36 questionnaire. SF-3612provides standardized scores ranging from 0–100 to measure eight health domains including role-physical domain, role-emotional domain, physical functioning, social functioning, mental health, vitality, bodily pain, and general health perceptions. Finally a physical component summery score and a mental component summery score is calculated using the scores obtained in the physical and mental domains respectively. Higher score represents better QoL. Of the 49 patients included 39 were men (80%) and 10 women (20%). QoL before surgery was significantly lower on all scales, except for bodily pain, than for the age matched general population. All patients underwent the Maze III operation and sinus rhythm was restored and maintained without antiarrhythmic medication in 90% of the 30 patients at 6 months follow-up. After surgery all scores were significantly improved except for bodily pain, which, was already normal before the operation, Table 2. Six months and 1 year after surgery QoL reached the levels of the age-matched general population. Lönnerholm et al. concluded that these results indicate that the Maze operation can be used in selected patients with drug-refractory paroxysmal or permanent AF as a primary indication for heart surgery. Table 2 QoL before and 6 months after the maze operation21 SF 36 variable . Baseline (n=30) . 6 months follow-up (n=30) . pa . Physical functioning 58.8±25.5 83.3±23.0 <0.001 Role limitation, physical 17.2±33.5 69.0±43.1 <0.001 Bodily pain 70.2±29.8 82.7±28.3 0.07 General health 56.1±15.6 76.7±21.1 0.001 Vitality 41.0±19.1 74.2±20.0 <0.001 Social functioning 58.5±24.4 87.2±21.0 <0.001 Role limitation, emotional 36.8±42.9 88.9±28.1 0.001 Mental health 64.8±18.3 78.3±20.0 0.008 SF 36 variable . Baseline (n=30) . 6 months follow-up (n=30) . pa . Physical functioning 58.8±25.5 83.3±23.0 <0.001 Role limitation, physical 17.2±33.5 69.0±43.1 <0.001 Bodily pain 70.2±29.8 82.7±28.3 0.07 General health 56.1±15.6 76.7±21.1 0.001 Vitality 41.0±19.1 74.2±20.0 <0.001 Social functioning 58.5±24.4 87.2±21.0 <0.001 Role limitation, emotional 36.8±42.9 88.9±28.1 0.001 Mental health 64.8±18.3 78.3±20.0 0.008 a SF-36 score at 6 months follow-up vs. baseline. Values are mean±SD. Open in new tab Table 2 QoL before and 6 months after the maze operation21 SF 36 variable . Baseline (n=30) . 6 months follow-up (n=30) . pa . Physical functioning 58.8±25.5 83.3±23.0 <0.001 Role limitation, physical 17.2±33.5 69.0±43.1 <0.001 Bodily pain 70.2±29.8 82.7±28.3 0.07 General health 56.1±15.6 76.7±21.1 0.001 Vitality 41.0±19.1 74.2±20.0 <0.001 Social functioning 58.5±24.4 87.2±21.0 <0.001 Role limitation, emotional 36.8±42.9 88.9±28.1 0.001 Mental health 64.8±18.3 78.3±20.0 0.008 SF 36 variable . Baseline (n=30) . 6 months follow-up (n=30) . pa . Physical functioning 58.8±25.5 83.3±23.0 <0.001 Role limitation, physical 17.2±33.5 69.0±43.1 <0.001 Bodily pain 70.2±29.8 82.7±28.3 0.07 General health 56.1±15.6 76.7±21.1 0.001 Vitality 41.0±19.1 74.2±20.0 <0.001 Social functioning 58.5±24.4 87.2±21.0 <0.001 Role limitation, emotional 36.8±42.9 88.9±28.1 0.001 Mental health 64.8±18.3 78.3±20.0 0.008 a SF-36 score at 6 months follow-up vs. baseline. Values are mean±SD. Open in new tab Although the study provides important information, there are several limitations that must be recognised. Firstly, no disease specific QoL measure was used and the study was without a control and a placebo group. As mentioned by Lönnerholm et al. a significant placebo effect of the surgical intervention is unlikely because the QoL at 1 year was essentially the same as that at 6 months. However, patients may be expected to be withdrawn from prestudy medication after surgery. It is unclear whether the marked improvements in measurement of QoL were related solely to the Maze operation. The removal of drug related adverse effects might have some effect. Secondly, the number of patients was very small with only 25 patients followed for 1-year. Thirdly, the study population was highly selected and severely impaired by their AF, which is evident from the low QoL scores before surgery. Furthermore, the included patients were heterogeneous in regard to the nature of the arrhythmia as well as to age (27 to 72 years). Finally, the fact that only 20% of the included patients were women in the present study cannot be ignored. This have become evident from other studies were QoL in AF have been assessed using the SF-36 questionnaire,22–24women have scored significantly worse than men indicating that the impact of AF on QoL is greater in women and findings obtained in a study population consisting of 80% men cannot be transferred to clinical settings with an even distribution of men and women. In a study by Jessurun et al.2541 patients with longstanding symptomatic, drug-refractory, lone paroxysmal AF underwent Maze III surgery. The primary end-point was to establish the effectiveness and safety of the Maze III operation. However, QoL was assessed before surgery and at 3 and 12 months after surgery in 18 patients using the SF-36 questionnaire.12After surgery all SF-36 scores were significantly improved except for bodily pain and role limitation. In other words the QoL results as well as the limitations in this study are almost identical to the study by Lönnerholm et al.21and indicates that the Maze operation has a positive effect on QoL in these highly selected patients groups. 5 Catheter ablation of atrial fibrillation Two catheter ablation techniques to modify the substrate of AF are currently under investigation, linear atrial ablation and focal atrial ablation. In linear atrial ablation, the so-called ‘Catheter maze’, the atria is compartmentalized to render it incapable of sustaining multiple wavefronts of electrical activity to maintain AF. In focal atrial ablation the first strategy involved mapping and ablation of the arrhythmogenic foci within the pulmonary veins. Due to a recurrence rate of at least 50% the ablation currently is targeted to the ostium of the pulmonary vein with the end-point of the procedure being to electrically isolate the pulmonary veins from the rest of the left atrium. However, the recurrence rate is still high (40–50%) and the optimal strategy still remains to be found. Hypothetically the combination of catheter maze and focal atrial ablation may be associated with a lower risk of AF recurrence.1 Pappone et al.26compared the impact of pulmonary vein ablation on QoL with medical therapy. QoL were measured in 109 patients undergoing pulmonary vein ablation and 102 patients receiving rhythm control therapy using, SF-3612at the time of admission and at 3-moth intervals up to 1 year. QoL assessed by the SF-36 summery scores (physical and mental) increased significantly after the ablation where as there were no significant changes in the rhythm control group. The authors conclude that pulmonary vein ablation improves QoL. However, there are several important limitations: the study is not randomised, the nature of the AF is not specified, it is not clear whether the patient were in sinus rhythm when completing the questionnaires, and only one QoL instrument is used. In a study by Gerstenfeld et al.2771 patients underwent attempted pulmonary vein ablation and QoL were evaluated one month before and 6 months after electrophysiologic study using a modified version of SF-3612in combination with a 19 item symptom questionnaire. The 41 patients who completed both initial and follow-up questionnaires were divided into three groups: those undergoing invasive mapping but in whom no ablation was performed (11 patients); those having undergone invasive mapping and ablation but in whom AF recurred (18 patients); and those having undergone successful ablation and remained in sinus rhythm (12 patients). Patients in the latter group reported significant improvement in QoL and reduction in all symptoms. Interestingly, the group of patients who underwent ablation but had recurrent AF also reported significant improvements in symptoms and QoL although not as large as those without recurrence of AF. These improvements were all greater than those experienced by patients undergoing intracardiac mapping without ablation, making a placebo effect unlikely. In conclusion both studies report significant improvement in QoL after pulmonary vein ablation; however with a recurrence rate at 68% and a risk of pulmonary vein stenoses at 8% in the study by Gerstenfeld et al. the method is far from being treatment of first choice. 6 Catheter based ablation or modification of the AV node Palliative ablation therapy for AF is well established for patients with disabling symptoms caused by a rapid ventricular rate who are refractory to or who do not tolerate pharmacologic therapy. The rationale for ablation of the AV conduction system with implantation of a pacemaker is that it is almost always easier to treat bradycardias than tachycardias. However, is must be emphasized that ablation of the AV node is permanent and irreversible. It renders the patient pacemaker dependent with the associated risk of pacemaker failure, lead malfunction, and need for re-implantation. Furthermore, the procedure has no impact on AF nor alter the thromboembolic risk. 6.1 AV node ablation and pacemaker implantation A number of longitudinal studies have evaluated the effect of AV node ablation and pacemaker implantation on QoL. Summaries of these studies appear in Tables 3 and 4. The studies summarised in Table 3are purely descriptive with no control groups and no randomization. Only the studies by Bubien et al.14and The Ablate and Pace trial, APT,33have used validated QoL questionnaires. Bubien et al.14used a battery of 4 QoL measures before ablation and 1 and 6 months after ablation. A generic instrument, the SF-36 questionnaire, and a disease-specific instrument The Symptom checklist:Frequency and Severity. The latter is intended to measure the patient’s perception of the frequency and severity of symptoms related to the arrhythmias. Furthermore Bubien et al. included two investigator developed non-validated instruments: Perceived Impact of the arrhythmia on Activities of Daily Living and Performance of Activities of Daily Living. A major limitation in this study is the heterogeneity of the arrhythmias included. Only 22 patients had AF and the nature of AF i.e. paroxysmatic, persistent or permanent is not specified. Table 3 Summary of QoLaaspects of studies in patients undergoing AVbnode ablation and pacemaker implantation Study . Design . Intervention . Instrument(s) . . QoL results . . Limitations . . Kay et al.,281988 Longitudinal (6 weeks) 12 patients with paroxysmal AF AV junction ablation and VVIc-R PMd McMaster Health Index Questionnaire Scores in both measures increased significantly from before ablation to 6 weeks after ablation Small sample size Physiological General Well-Being Index Short follow-up time No control group Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Rosenqvistet al.,291990 Longitudinal (41±23 months) 47 patients, 29 with AFeor atrial flutter AV junction ablation and VVI, VVI-R, or DDDfPM Interview 83% of 42 patients reported improved activity level No validated QoL instrument No control group Highly selected severely symptomatic patients Heterogeneity of arrhythmias Time of interview unknown No information on interview method Olgin and Scheinman,301993 Longitudinel (41±23 months). 103 patients, 73 with AF or atrial flutter Radiofrequency AV junction ablation and VVI-R, DDI-R, or DDD PM compared with direct current catheter ablation Interview 83% reported improved condition after ablation No validated QoL instrument No control group Highly selected severely symptomatic patients Heterogeneity of arrhythmias Time of interview unknown No information on interview method Fitzpatricket al.,311996 Retrospective, cross-sectional review of patients medical cards and telephone survey. 90 patients with paroxysmal (n=36) and established (n=54) AF. AV junction ablation and DDD PM if paroxysmal AF and VVI PM if permanent AF Semiquantitative questionnaire on QoL, symptoms and ADL Significant improved QoL and reduced consumption of health care resources after AV junction ablation No validated QoL instrument Registration of health care consumption Retrospective nature No control group Highly selected severely symptomatic patients Bubien et al.,141996 Longitudinal (6 months). 161 patients with supraventricular or ventricular arrhythmia including 22 with AF Radiofrequency catheter ablation SF-36 AF patients had poorer QoL at baseline than patients with other arrhythmias Heterogeneity of arrhythmias Symptom checklist: frequency and severity No classification or description of AF Perceived impact on ADL Catheter ablation was associated with significant improvement in QoL Small sample size Perceived effect on ADL No control group Highly symptomatic selected patients The impact of withdrawal from antiarhythmic drug therapy on QoL is unknown Natale et al.,321996 Longitudinal (12 months). 12 patients with chronic AF. AV node ablation and VVI-R PM Self-administered questionnaire on palpitations, rest dyspnea, effort dyspnea, exercise tolerance, weakness, and perception of well-being The perception of well-being increased significantly after ablation and persisted over time No randomization No control group Small sample size No validated QoL instrument Kay et al.,331998 Longitudinal (12 months), multicenter. 156 patients with paroxysmal, recurrent or chronic AF. AV junction ablation and VVI or DDI PM Health Status Questionnaire (2.0) Significant improved QoL in all three measurements No randomization Quality of Life Index, Version III No control group Symptom checklist: frequency and severity Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Study . Design . Intervention . Instrument(s) . . QoL results . . Limitations . . Kay et al.,281988 Longitudinal (6 weeks) 12 patients with paroxysmal AF AV junction ablation and VVIc-R PMd McMaster Health Index Questionnaire Scores in both measures increased significantly from before ablation to 6 weeks after ablation Small sample size Physiological General Well-Being Index Short follow-up time No control group Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Rosenqvistet al.,291990 Longitudinal (41±23 months) 47 patients, 29 with AFeor atrial flutter AV junction ablation and VVI, VVI-R, or DDDfPM Interview 83% of 42 patients reported improved activity level No validated QoL instrument No control group Highly selected severely symptomatic patients Heterogeneity of arrhythmias Time of interview unknown No information on interview method Olgin and Scheinman,301993 Longitudinel (41±23 months). 103 patients, 73 with AF or atrial flutter Radiofrequency AV junction ablation and VVI-R, DDI-R, or DDD PM compared with direct current catheter ablation Interview 83% reported improved condition after ablation No validated QoL instrument No control group Highly selected severely symptomatic patients Heterogeneity of arrhythmias Time of interview unknown No information on interview method Fitzpatricket al.,311996 Retrospective, cross-sectional review of patients medical cards and telephone survey. 90 patients with paroxysmal (n=36) and established (n=54) AF. AV junction ablation and DDD PM if paroxysmal AF and VVI PM if permanent AF Semiquantitative questionnaire on QoL, symptoms and ADL Significant improved QoL and reduced consumption of health care resources after AV junction ablation No validated QoL instrument Registration of health care consumption Retrospective nature No control group Highly selected severely symptomatic patients Bubien et al.,141996 Longitudinal (6 months). 161 patients with supraventricular or ventricular arrhythmia including 22 with AF Radiofrequency catheter ablation SF-36 AF patients had poorer QoL at baseline than patients with other arrhythmias Heterogeneity of arrhythmias Symptom checklist: frequency and severity No classification or description of AF Perceived impact on ADL Catheter ablation was associated with significant improvement in QoL Small sample size Perceived effect on ADL No control group Highly symptomatic selected patients The impact of withdrawal from antiarhythmic drug therapy on QoL is unknown Natale et al.,321996 Longitudinal (12 months). 12 patients with chronic AF. AV node ablation and VVI-R PM Self-administered questionnaire on palpitations, rest dyspnea, effort dyspnea, exercise tolerance, weakness, and perception of well-being The perception of well-being increased significantly after ablation and persisted over time No randomization No control group Small sample size No validated QoL instrument Kay et al.,331998 Longitudinal (12 months), multicenter. 156 patients with paroxysmal, recurrent or chronic AF. AV junction ablation and VVI or DDI PM Health Status Questionnaire (2.0) Significant improved QoL in all three measurements No randomization Quality of Life Index, Version III No control group Symptom checklist: frequency and severity Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown a QoL, quality of life. b AV, atrioventricular node. c VVI(-R), ventricular demand pacing. d PM, pacemaker. e AF, atrial fibrillation. f DDD, DDI(-R), dual chamber pacing. Open in new tab Table 3 Summary of QoLaaspects of studies in patients undergoing AVbnode ablation and pacemaker implantation Study . Design . Intervention . Instrument(s) . . QoL results . . Limitations . . Kay et al.,281988 Longitudinal (6 weeks) 12 patients with paroxysmal AF AV junction ablation and VVIc-R PMd McMaster Health Index Questionnaire Scores in both measures increased significantly from before ablation to 6 weeks after ablation Small sample size Physiological General Well-Being Index Short follow-up time No control group Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Rosenqvistet al.,291990 Longitudinal (41±23 months) 47 patients, 29 with AFeor atrial flutter AV junction ablation and VVI, VVI-R, or DDDfPM Interview 83% of 42 patients reported improved activity level No validated QoL instrument No control group Highly selected severely symptomatic patients Heterogeneity of arrhythmias Time of interview unknown No information on interview method Olgin and Scheinman,301993 Longitudinel (41±23 months). 103 patients, 73 with AF or atrial flutter Radiofrequency AV junction ablation and VVI-R, DDI-R, or DDD PM compared with direct current catheter ablation Interview 83% reported improved condition after ablation No validated QoL instrument No control group Highly selected severely symptomatic patients Heterogeneity of arrhythmias Time of interview unknown No information on interview method Fitzpatricket al.,311996 Retrospective, cross-sectional review of patients medical cards and telephone survey. 90 patients with paroxysmal (n=36) and established (n=54) AF. AV junction ablation and DDD PM if paroxysmal AF and VVI PM if permanent AF Semiquantitative questionnaire on QoL, symptoms and ADL Significant improved QoL and reduced consumption of health care resources after AV junction ablation No validated QoL instrument Registration of health care consumption Retrospective nature No control group Highly selected severely symptomatic patients Bubien et al.,141996 Longitudinal (6 months). 161 patients with supraventricular or ventricular arrhythmia including 22 with AF Radiofrequency catheter ablation SF-36 AF patients had poorer QoL at baseline than patients with other arrhythmias Heterogeneity of arrhythmias Symptom checklist: frequency and severity No classification or description of AF Perceived impact on ADL Catheter ablation was associated with significant improvement in QoL Small sample size Perceived effect on ADL No control group Highly symptomatic selected patients The impact of withdrawal from antiarhythmic drug therapy on QoL is unknown Natale et al.,321996 Longitudinal (12 months). 12 patients with chronic AF. AV node ablation and VVI-R PM Self-administered questionnaire on palpitations, rest dyspnea, effort dyspnea, exercise tolerance, weakness, and perception of well-being The perception of well-being increased significantly after ablation and persisted over time No randomization No control group Small sample size No validated QoL instrument Kay et al.,331998 Longitudinal (12 months), multicenter. 156 patients with paroxysmal, recurrent or chronic AF. AV junction ablation and VVI or DDI PM Health Status Questionnaire (2.0) Significant improved QoL in all three measurements No randomization Quality of Life Index, Version III No control group Symptom checklist: frequency and severity Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Study . Design . Intervention . Instrument(s) . . QoL results . . Limitations . . Kay et al.,281988 Longitudinal (6 weeks) 12 patients with paroxysmal AF AV junction ablation and VVIc-R PMd McMaster Health Index Questionnaire Scores in both measures increased significantly from before ablation to 6 weeks after ablation Small sample size Physiological General Well-Being Index Short follow-up time No control group Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Rosenqvistet al.,291990 Longitudinal (41±23 months) 47 patients, 29 with AFeor atrial flutter AV junction ablation and VVI, VVI-R, or DDDfPM Interview 83% of 42 patients reported improved activity level No validated QoL instrument No control group Highly selected severely symptomatic patients Heterogeneity of arrhythmias Time of interview unknown No information on interview method Olgin and Scheinman,301993 Longitudinel (41±23 months). 103 patients, 73 with AF or atrial flutter Radiofrequency AV junction ablation and VVI-R, DDI-R, or DDD PM compared with direct current catheter ablation Interview 83% reported improved condition after ablation No validated QoL instrument No control group Highly selected severely symptomatic patients Heterogeneity of arrhythmias Time of interview unknown No information on interview method Fitzpatricket al.,311996 Retrospective, cross-sectional review of patients medical cards and telephone survey. 90 patients with paroxysmal (n=36) and established (n=54) AF. AV junction ablation and DDD PM if paroxysmal AF and VVI PM if permanent AF Semiquantitative questionnaire on QoL, symptoms and ADL Significant improved QoL and reduced consumption of health care resources after AV junction ablation No validated QoL instrument Registration of health care consumption Retrospective nature No control group Highly selected severely symptomatic patients Bubien et al.,141996 Longitudinal (6 months). 161 patients with supraventricular or ventricular arrhythmia including 22 with AF Radiofrequency catheter ablation SF-36 AF patients had poorer QoL at baseline than patients with other arrhythmias Heterogeneity of arrhythmias Symptom checklist: frequency and severity No classification or description of AF Perceived impact on ADL Catheter ablation was associated with significant improvement in QoL Small sample size Perceived effect on ADL No control group Highly symptomatic selected patients The impact of withdrawal from antiarhythmic drug therapy on QoL is unknown Natale et al.,321996 Longitudinal (12 months). 12 patients with chronic AF. AV node ablation and VVI-R PM Self-administered questionnaire on palpitations, rest dyspnea, effort dyspnea, exercise tolerance, weakness, and perception of well-being The perception of well-being increased significantly after ablation and persisted over time No randomization No control group Small sample size No validated QoL instrument Kay et al.,331998 Longitudinal (12 months), multicenter. 156 patients with paroxysmal, recurrent or chronic AF. AV junction ablation and VVI or DDI PM Health Status Questionnaire (2.0) Significant improved QoL in all three measurements No randomization Quality of Life Index, Version III No control group Symptom checklist: frequency and severity Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown a QoL, quality of life. b AV, atrioventricular node. c VVI(-R), ventricular demand pacing. d PM, pacemaker. e AF, atrial fibrillation. f DDD, DDI(-R), dual chamber pacing. Open in new tab Table 4 Summary of QoLastudies of AVbnode ablation versus medical treatment Study . Design . Intervention . . Instrument(s) . . QoL results . . Limitations . . Brignole et al.,361994 Randomized, longitudinal. 23 patients with chronic AF or atrial flutter and moderately impaired left ventricular function (mean LVEFc46%). Two-phase study Self-administered semiquantitative questionnaire on five symptoms (palpitations, rest dyspnea, effort dyspnea, exercise intolerance and asthenia. After 15 days symptoms decreased more in patients undergoing ablation. No validated QoL instrument 1. Randomized to AV junction ablation and VVI-RdPM or VVI-R PM only. 15 days follow-up. After 3 months improvement in symptoms were associated with improvement in functional class (NYHAe, exercise duration) Small sample size 2. The remaining patients underwent AV junction ablation. 3 months follow-up. Short follow-up Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Brignole et al.,351997 Randomized, longitudinal (6 months), multicenter. 43 patients with paroxysmal AFf. Randomization to: AV junction ablation and DDDg-R PM or antiarrhytmic drug treatment Minnesota Living With Heart Failure Questionnaire41 PMhimplantation was effective and superior to drug treatment in controlling symptoms and improving QoL Highly selected severely symptomatic patients Specific Symptoms Scale Small sample size Short follow-up The impact of drug-related adverse effects on QoL is unknown Brignole et al.,371998 Randomized, longitudinal (12 months), multicenter. 60 patients with HFiand chronic AF. Moderately impaired left ventricular function (mean LVEF 43%). Randomization to: AV junction ablation and VVI-R PM or antiarrhytmic drug treatment Minnesota Living With Heart Failure Questionnaire (LHQF)41 PM implantation was effective and superior to drug treatment in controlling symptoms Highly selected severely symptomatic patients Specific Symptoms Scale No significant benefit on LHQF and NYHA Crossover from drug treatment to PM (12%) Natale et al.,391999 Longitudinal consecutive (6 months), multicenter. 75 patients with chronic AF and moderately impaired left ventricular function (mean LVEF 40%). Patients were assigned to one of three groups Quality of Life Enjoyment and Satisfaction Questionnaire Group 1: all variables assessed improved significantly Non-randomized 1. AV ablation, VVIR PM and drug withdrawal Symptom score Group 2: all variables assessed improved, some significantly The questionnaires have not been validated in the present population 2. AV ablation, VVIR PM and continued medication Performance of specific activities Group 3: No change in the assessed variables No placebo medication in group 1 3. VVIR PM and continued medication Perception of well-being Levy et al.,382001 Randomized, longitudinal (12 months) 36 patients with permanent AF and normal left ventricular function. Randomization to: His ablation and VVI-R PM or AV modifying drugs and VVI PM Karolinska questionnaire Similar QoL in the two groups. Small sample size. Nottingham health profile Significant QoL improvement in both groups after treatment No control group Highly selected severely symptomatic patients Study . Design . Intervention . . Instrument(s) . . QoL results . . Limitations . . Brignole et al.,361994 Randomized, longitudinal. 23 patients with chronic AF or atrial flutter and moderately impaired left ventricular function (mean LVEFc46%). Two-phase study Self-administered semiquantitative questionnaire on five symptoms (palpitations, rest dyspnea, effort dyspnea, exercise intolerance and asthenia. After 15 days symptoms decreased more in patients undergoing ablation. No validated QoL instrument 1. Randomized to AV junction ablation and VVI-RdPM or VVI-R PM only. 15 days follow-up. After 3 months improvement in symptoms were associated with improvement in functional class (NYHAe, exercise duration) Small sample size 2. The remaining patients underwent AV junction ablation. 3 months follow-up. Short follow-up Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Brignole et al.,351997 Randomized, longitudinal (6 months), multicenter. 43 patients with paroxysmal AFf. Randomization to: AV junction ablation and DDDg-R PM or antiarrhytmic drug treatment Minnesota Living With Heart Failure Questionnaire41 PMhimplantation was effective and superior to drug treatment in controlling symptoms and improving QoL Highly selected severely symptomatic patients Specific Symptoms Scale Small sample size Short follow-up The impact of drug-related adverse effects on QoL is unknown Brignole et al.,371998 Randomized, longitudinal (12 months), multicenter. 60 patients with HFiand chronic AF. Moderately impaired left ventricular function (mean LVEF 43%). Randomization to: AV junction ablation and VVI-R PM or antiarrhytmic drug treatment Minnesota Living With Heart Failure Questionnaire (LHQF)41 PM implantation was effective and superior to drug treatment in controlling symptoms Highly selected severely symptomatic patients Specific Symptoms Scale No significant benefit on LHQF and NYHA Crossover from drug treatment to PM (12%) Natale et al.,391999 Longitudinal consecutive (6 months), multicenter. 75 patients with chronic AF and moderately impaired left ventricular function (mean LVEF 40%). Patients were assigned to one of three groups Quality of Life Enjoyment and Satisfaction Questionnaire Group 1: all variables assessed improved significantly Non-randomized 1. AV ablation, VVIR PM and drug withdrawal Symptom score Group 2: all variables assessed improved, some significantly The questionnaires have not been validated in the present population 2. AV ablation, VVIR PM and continued medication Performance of specific activities Group 3: No change in the assessed variables No placebo medication in group 1 3. VVIR PM and continued medication Perception of well-being Levy et al.,382001 Randomized, longitudinal (12 months) 36 patients with permanent AF and normal left ventricular function. Randomization to: His ablation and VVI-R PM or AV modifying drugs and VVI PM Karolinska questionnaire Similar QoL in the two groups. Small sample size. Nottingham health profile Significant QoL improvement in both groups after treatment No control group Highly selected severely symptomatic patients a QoL, quality of life. b AV, atrioventricular node. c LVEF, left ventricular ejection fraction. d VVI(-R), ventricular demand pacing. e NYHA, New York Heart Association functional class. f AF, atrial fibrillation. g DDD, DDI(-R), dual chamber pacing. h PM, pacemaker. i HF, heart failure. Open in new tab Table 4 Summary of QoLastudies of AVbnode ablation versus medical treatment Study . Design . Intervention . . Instrument(s) . . QoL results . . Limitations . . Brignole et al.,361994 Randomized, longitudinal. 23 patients with chronic AF or atrial flutter and moderately impaired left ventricular function (mean LVEFc46%). Two-phase study Self-administered semiquantitative questionnaire on five symptoms (palpitations, rest dyspnea, effort dyspnea, exercise intolerance and asthenia. After 15 days symptoms decreased more in patients undergoing ablation. No validated QoL instrument 1. Randomized to AV junction ablation and VVI-RdPM or VVI-R PM only. 15 days follow-up. After 3 months improvement in symptoms were associated with improvement in functional class (NYHAe, exercise duration) Small sample size 2. The remaining patients underwent AV junction ablation. 3 months follow-up. Short follow-up Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Brignole et al.,351997 Randomized, longitudinal (6 months), multicenter. 43 patients with paroxysmal AFf. Randomization to: AV junction ablation and DDDg-R PM or antiarrhytmic drug treatment Minnesota Living With Heart Failure Questionnaire41 PMhimplantation was effective and superior to drug treatment in controlling symptoms and improving QoL Highly selected severely symptomatic patients Specific Symptoms Scale Small sample size Short follow-up The impact of drug-related adverse effects on QoL is unknown Brignole et al.,371998 Randomized, longitudinal (12 months), multicenter. 60 patients with HFiand chronic AF. Moderately impaired left ventricular function (mean LVEF 43%). Randomization to: AV junction ablation and VVI-R PM or antiarrhytmic drug treatment Minnesota Living With Heart Failure Questionnaire (LHQF)41 PM implantation was effective and superior to drug treatment in controlling symptoms Highly selected severely symptomatic patients Specific Symptoms Scale No significant benefit on LHQF and NYHA Crossover from drug treatment to PM (12%) Natale et al.,391999 Longitudinal consecutive (6 months), multicenter. 75 patients with chronic AF and moderately impaired left ventricular function (mean LVEF 40%). Patients were assigned to one of three groups Quality of Life Enjoyment and Satisfaction Questionnaire Group 1: all variables assessed improved significantly Non-randomized 1. AV ablation, VVIR PM and drug withdrawal Symptom score Group 2: all variables assessed improved, some significantly The questionnaires have not been validated in the present population 2. AV ablation, VVIR PM and continued medication Performance of specific activities Group 3: No change in the assessed variables No placebo medication in group 1 3. VVIR PM and continued medication Perception of well-being Levy et al.,382001 Randomized, longitudinal (12 months) 36 patients with permanent AF and normal left ventricular function. Randomization to: His ablation and VVI-R PM or AV modifying drugs and VVI PM Karolinska questionnaire Similar QoL in the two groups. Small sample size. Nottingham health profile Significant QoL improvement in both groups after treatment No control group Highly selected severely symptomatic patients Study . Design . Intervention . . Instrument(s) . . QoL results . . Limitations . . Brignole et al.,361994 Randomized, longitudinal. 23 patients with chronic AF or atrial flutter and moderately impaired left ventricular function (mean LVEFc46%). Two-phase study Self-administered semiquantitative questionnaire on five symptoms (palpitations, rest dyspnea, effort dyspnea, exercise intolerance and asthenia. After 15 days symptoms decreased more in patients undergoing ablation. No validated QoL instrument 1. Randomized to AV junction ablation and VVI-RdPM or VVI-R PM only. 15 days follow-up. After 3 months improvement in symptoms were associated with improvement in functional class (NYHAe, exercise duration) Small sample size 2. The remaining patients underwent AV junction ablation. 3 months follow-up. Short follow-up Highly selected severely symptomatic patients The impact of drug-related adverse effects on QoL is unknown Brignole et al.,351997 Randomized, longitudinal (6 months), multicenter. 43 patients with paroxysmal AFf. Randomization to: AV junction ablation and DDDg-R PM or antiarrhytmic drug treatment Minnesota Living With Heart Failure Questionnaire41 PMhimplantation was effective and superior to drug treatment in controlling symptoms and improving QoL Highly selected severely symptomatic patients Specific Symptoms Scale Small sample size Short follow-up The impact of drug-related adverse effects on QoL is unknown Brignole et al.,371998 Randomized, longitudinal (12 months), multicenter. 60 patients with HFiand chronic AF. Moderately impaired left ventricular function (mean LVEF 43%). Randomization to: AV junction ablation and VVI-R PM or antiarrhytmic drug treatment Minnesota Living With Heart Failure Questionnaire (LHQF)41 PM implantation was effective and superior to drug treatment in controlling symptoms Highly selected severely symptomatic patients Specific Symptoms Scale No significant benefit on LHQF and NYHA Crossover from drug treatment to PM (12%) Natale et al.,391999 Longitudinal consecutive (6 months), multicenter. 75 patients with chronic AF and moderately impaired left ventricular function (mean LVEF 40%). Patients were assigned to one of three groups Quality of Life Enjoyment and Satisfaction Questionnaire Group 1: all variables assessed improved significantly Non-randomized 1. AV ablation, VVIR PM and drug withdrawal Symptom score Group 2: all variables assessed improved, some significantly The questionnaires have not been validated in the present population 2. AV ablation, VVIR PM and continued medication Performance of specific activities Group 3: No change in the assessed variables No placebo medication in group 1 3. VVIR PM and continued medication Perception of well-being Levy et al.,382001 Randomized, longitudinal (12 months) 36 patients with permanent AF and normal left ventricular function. Randomization to: His ablation and VVI-R PM or AV modifying drugs and VVI PM Karolinska questionnaire Similar QoL in the two groups. Small sample size. Nottingham health profile Significant QoL improvement in both groups after treatment No control group Highly selected severely symptomatic patients a QoL, quality of life. b AV, atrioventricular node. c LVEF, left ventricular ejection fraction. d VVI(-R), ventricular demand pacing. e NYHA, New York Heart Association functional class. f AF, atrial fibrillation. g DDD, DDI(-R), dual chamber pacing. h PM, pacemaker. i HF, heart failure. Open in new tab The Ablate and Pace trial, APT (33) used tree validated self-administrered questionnaires: Health Status Questionnaire is a generic instrument, nearly identical to the, SF-36.12 Quality of Life Index, Version III34is a disease-specific instrument designed to measure QoL in a population of individuals with cardiac disorders. The Symptom Checklist: Frequency and Severity14is a disease-specific instrument intended to measure the patient’s perception of the frequency and severity of symptoms related to arrhythmias. After ablation and pacemaker implantation, significant improvements were seen in both the generic and the disease-specific QoL instruments as well as in arrhythmia related symptoms. However, the study was designed asa prospective registry rather than a controlled clinical trail. This makes it impossible to be certain that all of the changes in QoL were due to catheter ablation and pacemaker implantation. For example it is possible that some patients may have experienced improvements with continued medical treatment. In addition, patientsincluded were highly selected, severely symptomatic patients where no distinction between paroxysmatic, recurrent and chronic AF were made. It is important to remember that these study results should not be generalized to less severely compromised patients most frequently seen. 6.2 AV node ablation versus medical treatment The importance of medical ventricular rate control versus pacemaker mediated ventricular rhythm control have been evaluated in patients with persistent35and permanent36–39AF with normal35,38and moderately impaired left ventricular function.36,37,39These trials are summarised in.Table 4In a study by Brignole et al.37QoL were assessed longitudinally at the time of enrolment and at the end of the 12 month study period using the following measurements: The Minnesota Living With Heart Failure Questionnaire,40which is a well validated 21-item self-administered questionnaire that covers physical, socio-economic and psychological impairments. A score based on how each person ranks each item on a common scale is used to quantify the extent of impairment and how it is affected by therapeutic intervention. The Specific Symptom Scale is a disease-specific instrument used to measure the patient’s perception of the frequency and severity of arrhythmia related symptoms. At the end of the 12 months study, the ablation- and pacemaker-treated group had significantly better scores in the disease-specific symptoms in comparison with the drug group. However, there were no significant differences in the generic Minnesota Living with Heart Failure Questionnaire scores, with both methods demonstrating improvement over baseline. Because of the controlled design, the study demonstrates that not all the benefits were due to ablation and pacemaker treatment per se, as some improvement occurred also in the conventional treatment group. Levy et al.38assessed QoL using the following two instruments: Modified Karolinska Questionnaire, KQ, is a cardiac specific questionnaire that has been validated for pacemaker patients.15 The Nottingham health profile, NHP, is a general QoL instrument validated for cardiac patients.41It is divided into two parts. The first consists of six dimensions: physical, mobility, pain, sleep, energy, social isolation, and emotional reaction. The second part lists aspects of life that may be affected by the patients’ health. Both patient groups had significant improvement in total KQ scores and total NHP part 1 scores at all follow-ups. For inter-group comparison there was no significant difference in any baseline result or between groups in follow-up. For part 2 of the NHP there was no significant change from baseline in either group at any time or any difference between groups. Levy et al. conclude that in these patients improved rate control will lead to a significant improvement in exercise duration and QoL and that neither technique shows any significant advantage over the other. Overall the studies suggest that ablation may beadvantageous in patients with permanent AF when left ventricular function is moderately impaired. However, ablation offers no advantage in the presence of normal ventricular function if rate control can be achieved with AV blocking agents. The pragmatic clinical approach as purposed by Levy et al.38may be medical treatment first in combination with a VVI-R pacemaker as it avoids initial irreversible ablation. Ablation can eventually be performed at a later stage in non-responders. 6.3 AV node ablation versus AV node modification Partial AV node ablation, AV modification, has been tried as an alternative to AV node ablation. The objective of partial AV node ablation is to modify the conduction properties slowing the ventricular rate in AF without the need for pacemaker dependency. Unfortunately, AV node modification is technically difficult and long-term results often unpredictable. In contrast to the almost 100% success in AV node ablation, the success in AV node modification is approximately 70%.43QoL in patients undergoing AV node ablation or AV node modification have been compared in a longitudinal study44of 60 patients with medically refractory paroxysmal or chronic AF. The patients were randomly assigned to either complete AV nodal ablation with permanent VVI-R pacing or AV nodal modification. QoL was assessed before and at 1 and 6 months after ablation/modification using a QoL diary and a semiquantitative questionnaire. Both treatments were associated with a significant improvement in general QoL. Patients who received AV nodal modification remained symptomatic, perhapsbecause of their irregular ventricular rhythm of AF. In other words AV nodal ablation with permanent pacing had a significantly greater effect than AV nodal modification in decreasing the frequency of attacks and extent of symptoms of AF, and the patients who received this procedure were more satisfied with their general well-being. A major limitation in this study was the use of non-validated QoL instruments. Furthermore, no control group was incorporated and the follow-up time period was only 6 months. 7 Pacing management of atrial fibrillation Several investigators45,46have reported an increased incidence of AF with the use of ventricular pacing as compared with atrial or dual-chamber pacing. These findings have led to newer pacing techniques for the prevention of AF in selected patients. The theoretical rationale for multisite atrial pacing is that pacing from a second site can achieve a more synchronous activation of the atria thus preventing the occurrence of reentrant circuits.47Dual-site atrial pacing involves inserting one pacing lead in the right atrial appendage and the other pacing lead at the ostium of the coronary sinus.48The impact of dual site atrial pacing on QoL has been tested in two prospective randomized crossover trials,49,50Table 5. Table 5 Summary of QoLa in patients with atrial fibrillation undergoing pacemaker management Study . Design . Intervention . Instrument(s) . . QoLaresults . . Limitations . . Levy et al.,492001 Longitudinal (1 month), randomized crossover. 20 patients with paroxysmal AFb One month of dual-site atrial pacing and one month of right atrial pacing Karolinska questionnaire Improved QoL with both strategies Short crossover period Small sample size Only one QoL instrument Lau et al.,502001 Longitudinal(12 weeks) randomized crossover. 22 patients with paroxsysmal AFb Sotalol and 12 weeks of dual-site atrial pacing and 12 weeks of right site atrial pacing Medical Outcome Study Short-Form Health Survey No measurable difference in QoL between pacing and no pacing group Small sample size Symptom Checklist: Frequency and severity Single site pacing arm was not randomized Study . Design . Intervention . Instrument(s) . . QoLaresults . . Limitations . . Levy et al.,492001 Longitudinal (1 month), randomized crossover. 20 patients with paroxysmal AFb One month of dual-site atrial pacing and one month of right atrial pacing Karolinska questionnaire Improved QoL with both strategies Short crossover period Small sample size Only one QoL instrument Lau et al.,502001 Longitudinal(12 weeks) randomized crossover. 22 patients with paroxsysmal AFb Sotalol and 12 weeks of dual-site atrial pacing and 12 weeks of right site atrial pacing Medical Outcome Study Short-Form Health Survey No measurable difference in QoL between pacing and no pacing group Small sample size Symptom Checklist: Frequency and severity Single site pacing arm was not randomized a QoL, quality of life. b AF, atrial fibrillation. Open in new tab Table 5 Summary of QoLa in patients with atrial fibrillation undergoing pacemaker management Study . Design . Intervention . Instrument(s) . . QoLaresults . . Limitations . . Levy et al.,492001 Longitudinal (1 month), randomized crossover. 20 patients with paroxysmal AFb One month of dual-site atrial pacing and one month of right atrial pacing Karolinska questionnaire Improved QoL with both strategies Short crossover period Small sample size Only one QoL instrument Lau et al.,502001 Longitudinal(12 weeks) randomized crossover. 22 patients with paroxsysmal AFb Sotalol and 12 weeks of dual-site atrial pacing and 12 weeks of right site atrial pacing Medical Outcome Study Short-Form Health Survey No measurable difference in QoL between pacing and no pacing group Small sample size Symptom Checklist: Frequency and severity Single site pacing arm was not randomized Study . Design . Intervention . Instrument(s) . . QoLaresults . . Limitations . . Levy et al.,492001 Longitudinal (1 month), randomized crossover. 20 patients with paroxysmal AFb One month of dual-site atrial pacing and one month of right atrial pacing Karolinska questionnaire Improved QoL with both strategies Short crossover period Small sample size Only one QoL instrument Lau et al.,502001 Longitudinal(12 weeks) randomized crossover. 22 patients with paroxsysmal AFb Sotalol and 12 weeks of dual-site atrial pacing and 12 weeks of right site atrial pacing Medical Outcome Study Short-Form Health Survey No measurable difference in QoL between pacing and no pacing group Small sample size Symptom Checklist: Frequency and severity Single site pacing arm was not randomized a QoL, quality of life. b AF, atrial fibrillation. Open in new tab Although both studies have used well-validated QoL instruments and both studies are randomized and prospective there are important limitations. First, the small number of patients, a much larger population would have been required to demonstrate differences in QoL because of large variability of the measured parameters. Second, the short follow-up periods. However, it is noteworthy that neither of the studies demonstrated a beneficial effect of multisite atrial pacing on QoL. 8 Implantable atrial defibrillator In the currently used atrial defibrillator the shocks for AF can be activated by the patient or can be programmed to occur automatically in the early morning while the patient is asleep. Thus, this therapy provides some patient control over the treatment, which has lead to speculations concerning improved QoL.1Newman et al.51have evaluated the impact of QoL of patients implanted with atrial defibrillators. In the present study 144 patients with symptomatic AF or atrial tachycardia received an atrial defibrillator. QoL was assessed at baseline, 3 months post-implant, and 6 months post-implant using the SF-3612and The Symptom Checklist: Frequency and Severity.14 QoL assessments were available at baseline, after 3 and 6 months. Two of the subscales in the SF-36 (role-physical and vitality) improved significantly after the implantation. The other 8 SF-36 scales showed no decrease from pre-implant over time. Furthermore, symptoms decreased significantly from baseline to 3 and 6 months without a change in symptom severity. In other words the implantation of an atrial defibrillator increased some domains of QoL and decreased the frequency of symptoms in a small subgroup of patients with symptomatic, drug-refractory AF. However, other investigators have not confirmed the results and the lack of a control group is a major limitation when interpreting these findings. 9 Conclusion There is an increasing awareness that QoL is important and QoL has become a key issue in a growing number of clinical trials. However, despite the fact that AF is a very common disorder with profound impact in terms of morbidity and mortality, the currently available data from adequately designed studies are sparse. From the studies reviewed, the available data show that QoL is impaired in patients with AF and that the majority of patients after having underwent a nonpharmacologic treatment report enhanced QoL. There may be several reasons for these findings: Prior to the intervention all patients have been burdened by severe symptoms caused by AF and by side effects to antiarrhythmic drugs. Improvements in QoL are therefore more or less expected and similar improvements may not occur in less symptomatic populations. In most studies antiarrhythmic medication have been discontinued at the time of the intervention and it is not clear to which degree the improvement in QoL is related solely to the nonpharmacologic treatment or to the removal of drug related adverse effects. Participants who undergo an invasive procedure may report improvement in QoL simply as a result of being part of a treatment group.52 Underreporting of undesirable characteristics and over reporting of socially desirably characteristics might confound self-reporting methods.52 In longitudinal study designs with variables containing random errors (short-term intra-individual variations and measurement errors) the computed relation is biased by the regression towards the mean phenomenon. Consequently, the observed improvement in QoL before and after nonpharmacologic intervention is not caused by the intervention alone but reflects the effect of repeated measurements and the regression towards the mean phenomenon as well. Many of the methodological problems involved in the assessment of QoL have already been discussed in conjunction the relevant studies, however some of the major issues should be emphasized: Heterogeneity of study groups, which means that patients with different manifestations of AF as well as patients with different conduction disorders wereanalyzed together. As the impact of AF on QoL depends on the type of AF i.e. paroxysmal, persistent or permanent this heterogeneity is an important limitation when interpreting results. Many of the reviewed studies are descriptive with no control group and no blinding opening the door for possible investigator bias. The vast majority of the prospective studies have a short follow-up time and the long-term effects of any given pacemaker cannot be assessed. Short– and long-term results may very well differ which is apparent in the study by Lamas et al.53where there were no significant differences in disease-specific QoL at either three or at nine months. However, there was a significant difference favouring dual chamber pacing at the 18 months visit, and longitudinal analysis demonstrated a significant difference favouring dual-chamber pacing. In addition longer follow-up would make it possible to determine whether pacemaker patient’s QoL changed over time in association with aging and the development of comorbid states. Small sample size is a general problem limiting the statistical power in the reports. Only a few authors have accounted for sample size calculations and power levels. Some investigators seem to substitute QoL for other terms such as ‘health status’ or ‘functional status.’ The investigators often do not define what they conceptualize as QoL and they do not identify the specific domains of measurements that are supposed to denote QoL. Three randomised controlled trials have compared pharmacologic rate control therapy with pharmacologic rhythm control therapy using QoL as a secondary endpoint; The Pharmacological Intervention in Atrial Fibrillation (PIAF) study,54The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trail,55and the Rate Control versus Electrical Cardioversion (RACE) trail.56The studies show that rate control is as efficacious as rhythm control in improving QoL and challenge the concept that restoration of sinus rhythm in patients with AF is always an important goal. At first glance these results may appear contradictive to the improvements in QoL obtained in studies on nonpharmacologic treatment. A discrepancy that is readily explained looking at the patients enrolled in the trials. Patients in the AFFIRM and the PIAF are representative of the majority of patients with AF being elderly often mildly symptomatic, where as patients undergoing nonpharmacologic treatment are severely symptomatic, often younger patients referred to tertiary care. However, these results underline the need for an individualised treatment strategy with careful assessment of symptoms and underlying cardiac disease. Patients in whom AF causes symptoms despite pharmacologic therapy or who experience adverse drug effects may be candidates for nonpharmacologic treatment strategies and can expect improved QoL following such treatment. From the above reviewed studies it is apparent that the number of QoL instruments is overwhelming and that the wide variation in the instruments selected makes it difficult to compare QoL findings across studies. The following eight criteria may be useful when planning new studies as well as when evaluating the existing literature: Having a conceptual definition of QoL Identifying what dimensions of QoL are measured Specifying the rationale for the choice of measures selected Using at least one measure that is general in focus—i.e. a generic instrument At least one measure that is specific to the population of interest—i.e. a disease-specific Selecting measures with evidence of reliability and validity and reporting appropriately If appropriate, collecting data at several points in the treatment process to consider any change over time Asking patients to give an overall rating of their QoL Hopefully these criteria may act as an inspiration for investigators planning future studies thus enhancing the quality of quality of life research in nonpharmacologic treatment of AF. References 1 Bubien RS , Sanchez JE. Atrial fibrillation: treatment rationale and clinical utility of nonpharmacologic therapies. AACN Clin Issues . 2001 ; 12 : 140 –155. 2 Frost L , Engholm G, Moller H et al. Decrease in mortality in patients with a hospital diagnosis of atrial fibrillation in Denmark during the period 1980–1993. Eur Heart J . 1999 ; 20 : 1592 –1599. 3 Stewart S , MacIntyre K, MacLeod MM et al. Trends in hospital activity, morbidity and case fatality related to atrial fibrillation in Scotland, 1986–1996. Eur Heart J . 2001 ; 22 : 693 –701. 4 Wolf PA , Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke . 1991 ; 22 : 983 –988. 5 Fuster V , Ryden LE, Asinger RW et al. ACC/AHA/ESC Guidelines for the Management of Patients with atrial fibrillation: executive summary a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences. Developed in collaboration with the North American Society of Pacing and Electrophysiology. Circulation . 2001 ; 104 : 2118 –2150. 6 Plumb VJ , Windecker S, Epstein AE et al. Nonpharmacologic Therapy of Atrial Fibrillation and Atrial Flutter. Am J Geriatr Cardiol . 1998 ; 7 : 21 –26. 7 Dorian P , Jung W, Newman D et al. The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J Am Coll Cardiol . 2000 ; 36 : 1303 –1309. 8 Sanders C , Egger M, Donovan J et al. Reporting on quality of life in randomised controlled trials: bibliographic study. BMJ . 1998 ; 317 : 1191 –1194. 9 Fitzpatrick R , Fletcher A, Gore S et al. Quality of life measures in health care. I: Applications and issues in assessment. BMJ . 1992 ; 305 : 1074 –1077. 10 Gill TM , Feinstein AR. A critical appraisal of the quality of quality-of-life measurements. JAMA . 1994 ; 272 : 619 –626. 11 Testa MA , Simonson DC. Assesment of quality-of-life outcomes. N Engl J Med . 1996 ; 334 : 835 –840. 12 McHorney CA , Ware JE Jr., Lu JF et al. The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care . 1994 ; 32 : 40 –66. 13 Fletcher A , Gore S, Jones D et al. Quality of life measures in health care. II: Design, analysis, and interpretation. BMJ . 1992 ; 305 : 1145 –1148. 14 Bubien RS , Knotts-Dolson SM, Plumb VJ et al. Effect of radiofrequency catheter ablation on health-related quality of life and activities of daily living in patients with recurrent arrhythmias. Circulation . 1996 ; 94 : 1585 –1591. 15 Linde C . How to evaluate quality-of-life in pacemaker patients: problems and pitfalls. Pacing Clin. Electrophysiol . 1996 ; 19 : 391 –397. 16 Higginson IJ , Carr AJ. Measuring quality of life: Using quality of life measures in the clinical setting. BMJ . 2001 ; 322 : 1297 –1300. 17 Obias-Manno D , Friedmann E, Brooks MM et al. Adherence and arrhythmic mortality in the cardiac arrhythmia suppression trial (CAST). Ann Epidemiol . 1996 ; 6 : 93 –101. 18 Stroke prevention in atrial fibrillation study. Final results. Circulation 1991;84:527–539. 19 Califf RM , Kramer JM. What have we learned from the calcium channel blocker controversy? Circulation . 1998 ; 97 : 1529 –1531. 20 Cox JL . Atrial transport function after the maze procedure for atrial fibrillation: a 10-year clinical experience. Am Heart J . 1998 ; 136 : 934 –936. 21 Lönnerholm S , Blomstrom P, Nilsson L et al. Effects of the Maze operation on health-related quality of life in patients with atrial fibrillation. Circulation . 2000 ; 101 : 2607 –2611. 22 Jenkins LS , Eleanor S, Brodsky M et al. Quality of life in patients with atrial fibrillation: baseline data from AFFIRM. Circulation . 2000 ; 102 (Suppl II): II-512 Abstract. 23 Paquette M , Roy D, Talajic M et al. Role of gender and personality on quality-of-life impairment in intermittent atrial fibrillation. Am J Cardiol . 2000 ; 86 : 764 –768. 24 Bygrave AJ , Waktare JEP, Camm AJ. Gender differences in ‘quality of life’ in atrial fibrillation. J Am Coll Cardiol . 1999 ; 33 : 104A Abstract. 25 Jessurun ER , van Hemel NM, Defauw JAMT et al. Results of Maze surgery for lone paroxysmal atrial fibrillation. Circulation . 2000 ; 101 : 1559 –1567. 26 Pappone C , Rosanio S, Augello G et al. Quality of life after circumferential pulmonary vein ablation for atrial fibrillation. Circulation . 2002 ; 106 : 499 Abstract. 27 Gerstenfeld EP , Guerra P, Sparks PB et al. Clinical outcome after radiofrequency catheter ablation of focal atrial fibrillation triggers. J Cardiovasc Electrophysiol . 2001 ; 12 : 900 –908. 28 Kay GN , Bubien RS, Epstein AE et al. Effect of catheter ablation of the atrioventricular junction on quality of life and exercise tolerance in paroxysmal atrial fibrillation. Am J Cardiol . 1988 ; 62 : 741 –744. 29 Rosenquvist M , Lee MA, Moulinier L et al. Long-term follow-up of patients after transcatheter direct current ablation of the atrioventricular junction. J Am Coll Cardiol . 1990 ; 16 : 1467 –1474. 30 Olgin JE , Scheinman MM. Comparison of high energy direct current and radiofrequency catheter ablation of the atrioventricular junction. J Am Coll Cardiol . 1993 ; 21 : 557 –564. 31 Fitzpatrick AP , Kourouyan HD, Siu A et al. Quality of life and outcomes after radiofrequency His-bundle catheter ablation and permanent pacemaker implantation: impact of treatment in paroxysmal and established atrial fibrillation. Am Heart J . 1996 ; 131 : 499 –507. 32 Natale A , Zimerman L, Tomassoni G et al. Impact on ventricular function and quality of life of transcatheter ablation of the atrioventricular junction in chronic atrial fibrillation with a normal ventricular response. Am J Cardiol . 1996 ; 78 : 1431 –1433. 33 Kay GN , Ellenbogen KA, Giudici M et al. The Ablate and Pace Trial: a prospective study of catheter ablation of the AV conduction system and permanent pacemaker implantation for treatment of atrial fibrillation. APT Investigators. J Interv Card Electrophysiol . 1998 ; 2 : 121 –135. 34 Ferrans CE , Powers MJ. Quality of life index: development and psychometric properties. ANS Adv Nurs Sci . 1985 ; 8 : 15 –24. 35 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: a randomized controlled study. Circulation . 1997 ; 96 : 2617 –2624. 36 Brignole M , Gianfranchi L, Menozzi C et al. Influence of atrioventricular junction radiofrequency ablation in patients with chronic atrial fibrillation and flutter on quality of life and cardiac performance. Am J Cardiol . 1994 ; 74 : 242 –246. 37 Brignole M , Menozzi C, Gianfranchi L et al. Assessment of atrioventricular junction ablation and VVIR pacemaker versus pharmacological treatment in patients with heart failure and chronic atrial fibrillation: a randomized, controlled study. Circulation . 1998 ; 98 : 953 –960. 38 Levy T , Walker S, Mason M et al. Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study. Heart . 2001 ; 85 : 171 –178. 39 Natale A , Zimerman L, Tomassoni G et al. AV node ablation and pacemaker implantation after withdrawal of effective rate-control medications for chronic atrial fibrillation: effect on quality of life and exercise performance. Pacing Clin Electrophysiol . 1999 ; 22 : 1634 –1639. 40 Rector TS , Cohn JN. Assessment of patient outcome with the Minnesota Living with Heart Failure questionnaire: reliability and validity during a randomized, double-blind, placebo-controlled trial of pimobendan. Pimobendan Multicenter Research Group. Am Heart J . 1992 ; 124 : 1017 –1025. 41 Pocock SJ , Henderson RA, Seed P et al. Quality of life, employment status, and anginal symptoms after coronary angioplasty or bypass surgery. 3-year follow-up in the Randomized Intervention Treatment of Angina (RITA) Trial. Circulation . 1996 ; 94 : 135 –142. 42 Caine N , Harrison SC, Sharples LD et al. Prospective study of quality of life before and after coronary artery bypass grafting. BMJ . 1991 ; 302 : 511 –516. 43 Twidale N , McDonald T, Nave K et al. Comparison of the effects of AV nodal ablation versus AV nodal modification in patients with congestive heart failure and uncontrolled atrial fibrillation. Pacing Clin Electrophysiol . 1998 ; 21 : 641 –651. 44 Lee SH , Chen SA, Tai CT et al. Comparisons of quality of life and cardiac performance after complete atrioventricular junction ablation and atrioventricular junction modification in patients with medically refractory atrial fibrillation. J Am Coll Cardiol . 1998 ; 31 : 637 –644. 45 Connolly SJ , Kerr CR, Gent M et al. Effects of physiologic pacing versus ventricular pacing on the risk of Stroke and death due to cardiovascular causes. N Engl J Med . 2000 ; 342 : 1385 –1391. 46 Andersen HR , Nielsen JC, Thomsen PE et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet . 1997 ; 350 : 1210 –1216. 47 Gillis AM . Pacing to prevent atrial fibrillation. Cardiol Clin . 2000 ; 18 : 25 –36. 48 Friedman PA , Hill MR, Hammill SC et al. Randomized prospective pilot study of long-term dual-site atrial pacing for prevention of atrial fibrillation. Mayo Clin Proc . 1998 ; 73 : 848 –854. 49 Levy T , Walker S, Rex S et al. No incremental benefit of multisite atrial pacing compared with right atrial pacing in patients with drug refractory paroxysmal atrial fibrillation. Heart . 2001 ; 85 : 48 –52. 50 Lau CP , Tse HF, Yu CM et al. Dual-site atrial pacing for atrial fibrillation in patients without bradycardia. Am J Cardiol . 2001 ; 88 : 371 –375. 51 Newman D , Dorian P, Schwartzman D et al. Effect of an implantable atrial defibrillator on health–related quality of life in patients with atrial tachyarrhytmias. Circulation . 2000 ; 102 (Suppl II): 715 Abstract. 52 Luderitz B , Jung W. Quality of life in patients with atrial fibrillation. Arch Intern Med . 2000 ; 160 : 1749 –1757. 53 Lamas GA , Orav EJ, Stambler BS et al. Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators. N Engl J Med . 1998 ; 338 : 1097 –1104. 54 Hohnloser SH , Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation — Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet . 2000 ; 356 : 1789 –1794. 55 The Atrial Fibrillation Follow-up Investigation of Rhythm Management. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347:1825–1833. 56 Hagens VE , Ranchor AV, van Sonderen E et al. Quality of life in pesistent atrial fibrillation in the RACE study. Circulation . 2002 ; 106 (Suppl II): II-634 Abstract. The European Society of Cardiology
TI - Quality of life in nonpharmacologic treatment of atrial fibrillation
JF - European Heart Journal
DO - 10.1016/S0195-668X(03)00241-0
DA - 2003-08-01
UR - https://www.deepdyve.com/lp/oxford-university-press/quality-of-life-in-nonpharmacologic-treatment-of-atrial-fibrillation-9Okn9XJ08E
SP - 1387
EP - 1400
VL - 24
IS - 15
DP - DeepDyve
ER -