Atrial Fibrillation and Heart Failure — Five More Years
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《新英格兰医药杂志》
Heart failure is often complicated by atrial fibrillation, and atrial fibrillation can exacerbate and in some cases cause heart failure. Adverse effects of atrial fibrillation include a loss of atrial contribution to ventricular filling, a nonphysiologic heart-rate response, irregular periods of ventricular filling, and an increased risk of thromboembolism. In an editorial in the Journal five years ago,1 we observed that atrial fibrillation was associated with an adverse prognosis in several studies of heart failure, but it was not clear whether it directly increased disease progression and mortality or was only a marker for the severity of heart failure. Therapy with antiarrhythmic drugs to maintain sinus rhythm was disappointing, and there was concern that drug toxicity could offset the benefits of sinus rhythm. An individualized approach was recommended, with an emphasis on rate control and anticoagulation as the mainstays of therapy for persistent atrial fibrillation.
In the past five years, the association of atrial fibrillation with an adverse prognosis remains, although therapy with antiarrhythmic drugs has not improved. Randomized trials have shown that the "rhythm control strategy," whose goal is to maintain sinus rhythm with medication, increases the rate of hospitalization, with no improvement in mortality and no or little symptomatic benefit, as compared with the "rate control strategy." However, sinus rhythm was maintained for two to three years in only 40 to 73 percent of patients in the rhythm-control groups. Patients in whom sinus rhythm was maintained had better outcomes than did those with continued fibrillation, but it is still not clear whether patients in whom sinus rhythm was not maintained simply had more severe underlying heart failure.2 A minority of patients in these trials had heart failure. Most cardiologists can recall individual patients with heart failure whose condition appeared to improve in sinus rhythm and regress when atrial fibrillation recurred. A large multicenter trial is being conducted to evaluate whether the benefits of sinus rhythm in patients with heart failure are sufficiently great to offset the risks of therapy with antiarrhythmic drugs. Better therapies are still needed, but no new drugs have reached the market.
Nonpharmacologic therapies for atrial fibrillation have advanced rapidly. Surgery to correct arrhythmia abolishes atrial fibrillation in more than 90 percent of patients in some series, presumably by interrupting paths for reentry. However, because of the morbidity associated with the procedure, it is largely reserved for patients who also require valvular or coronary-artery bypass surgery.
In 1997, Jais et al.3 showed both that paroxysmal atrial fibrillation was initiated in some patients by triggering foci in the sleeves of musculature extending along the pulmonary veins and that catheter ablation of these triggers could abolish fibrillation. Multiple triggering foci were common. Ablation was often effective for paroxysmal atrial fibrillation but usually failed in patients with chronic atrial fibrillation.
From studies in animals and in humans, a picture of disease progression has emerged. Triggering foci cause paroxysmal atrial fibrillation, but with progressive atrial disease, modification of ionic currents and structural changes, including fibrosis in the atria outside the pulmonary veins, promote reentry. Catheter-ablation procedures have evolved and have become more extensive, encircling the antra of all pulmonary veins (Figure 1) and often incorporating additional connecting lines of ablation lesions that are likely to interrupt potential reentry paths.4 Although there is controversy about the best location for placement of the lesion and the importance of preventing triggers, as compared with interrupting the substrate for reentry paths, it seems likely that current ablation procedures have an effect on both the triggering foci and the reentry substrate. Some triggers are clearly outside the veins, and some reentry paths probably involve the ostial regions of the pulmonary vein. At experienced centers, practitioners now report rates of success of 75 percent or more among patients with paroxysmal atrial fibrillation. However, among patients with chronic atrial fibrillation, atrial dilatation, or impaired ventricular function, lower success rates (60 percent or less) have been reported.
Figure 1. A Three-Dimensional Reconstruction of the Left Atrium and Pulmonary Veins Viewed from the Right Posterior Position.
The inset at the right shows the right inferior pulmonary veins as viewed from the inside of the atrium. Ablation lesions would typically be placed along the white dashed line to encircle the antrum of the veins.
In this issue of the Journal, Hsu et al.5 report the outcome of catheter ablation in a consecutive series of patients with heart failure and atrial fibrillation in whom therapy with antiarrhythmic drugs had failed. Ablation (with additional therapy with antiarrhythmic drugs in approximately 10 percent of patients) achieved sinus rhythm in 78 percent of patients during a mean follow-up period of one year. After ablation, left ventricular function convincingly improved, with the ejection fraction returning to normal in 72 percent of patients. Symptoms and exercise capacity also improved. It is interesting to note that ventricular function improved even in patients with previously good heart-rate control. That finding indicates either that the degree of heart-rate control was still overestimated, despite a 48-hour recording time, or that the irregularity of the rhythm itself contributed to depressed ventricular function in some patients.
It should be recognized that these patients may not be typical of the average patient with heart failure and atrial fibrillation. They were referred to a center that is widely known for work in ablation, perhaps at a time when referring physicians thought that atrial fibrillation in particular was contributing to the aggravation of heart failure or that rate control was especially difficult. Even so, such patients are probably common, since the effect of atrial fibrillation on heart failure and the importance of achieving rate control at rest and with exertion are often underappreciated.
These results are encouraging, but a cautious approach is warranted. Catheter ablation of atrial fibrillation is a relatively recent procedure that continues to evolve. The present study lacks a control group of patients with heart failure and confirmation of long-term maintenance of initial benefits. The findings are consonant, however, with the results of a nonrandomized cohort study by Pappone et al., which showed that 589 patients who were treated with ablation had lower rates of mortality and morbidity, including stroke and heart failure, than did a contemporaneous group of 582 patients with atrial fibrillation who were treated medically.4 Catheter ablation of atrial fibrillation is a technically challenging procedure. In the study by Hsu et al., approximately half of the patients underwent two ablation procedures because of early recurrences of arrhythmia. Although early recurrent arrhythmias can spontaneously resolve with further maturation of the ablation lesions, waiting for spontaneous resolution may be problematic in patients with heart failure. The learning curve for the procedure and the potential risks are substantial. In the present series, major complications included stroke and cardiac tamponade. A large review recently reported symptomatic pulmonary-vein stenosis in approximately 4 percent of patients.6 Fatal atrial esophageal fistulae have only recently been recognized as a potential complication. Further technical improvements are needed, and more studies of safety and efficacy will be welcome. Whether anticoagulation should be discontinued, as was done in this trial, requires further evaluation, since asymptomatic recurrences are common in some studies.
The present study provides further evidence that some patients with atrial fibrillation and heart failure stand to benefit from restoration of sinus rhythm if that goal can be achieved without adverse effects of treatment. Further improvements are needed to make ablation easier and safer before it will be available outside highly experienced centers. Five years from now, will ablation for rhythm control be a first line of therapy for atrial fibrillation? The development of antiarrhythmic drugs that act specifically on the atrial myocardium without causing ventricular proarrhythmia appears to be feasible. Catheter ablation is easier for rate control than for rhythm control. Creating heart block and implanting a permanent pacemaker provide regularization of the ventricular rate, and the use of biventricular pacemakers may prevent an adverse effect of right ventricular pacing on left ventricular function. As in all cases of cardiac disease, the best long-term hope lies with therapies that provide protection against atrial fibrillation by preventing the initial development of atrial fibrosis and remodeling.
Dr. William Stevenson reports having received consulting and lecture fees and grant support from Biosense Webster and lecture fees from CryoCath Technologies. Dr. Lynne Stevenson reports having received consulting fees and grant support from Medtronics.
Source Information
From the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston.
References
Stevenson WG, Stevenson LW. Atrial fibrillation in heart failure. N Engl J Med 1999;341:910-911.
Corley SD, Epstein AE, DiMarco JP, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation 2004;109:1509-1513.
Jais P, Haissaguerre M, Shah DC, et al. A focal source of atrial fibrillation treated by discrete radiofreqency ablation. Circulation 1997;95:572-576.
Pappone C, Rosanio S, Augello G, et al. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol 2003;42:185-197.
Hsu L-F, Ja?s P, Sanders P, et al. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004;351:2373-2383.
Saad EB, Rossillo A, Saad CP, et al. Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation: functional characterization, evolution, and influence of the ablation strategy. Circulation 2003;108:3102-3107.(William G. Stevenson, M.D)
In the past five years, the association of atrial fibrillation with an adverse prognosis remains, although therapy with antiarrhythmic drugs has not improved. Randomized trials have shown that the "rhythm control strategy," whose goal is to maintain sinus rhythm with medication, increases the rate of hospitalization, with no improvement in mortality and no or little symptomatic benefit, as compared with the "rate control strategy." However, sinus rhythm was maintained for two to three years in only 40 to 73 percent of patients in the rhythm-control groups. Patients in whom sinus rhythm was maintained had better outcomes than did those with continued fibrillation, but it is still not clear whether patients in whom sinus rhythm was not maintained simply had more severe underlying heart failure.2 A minority of patients in these trials had heart failure. Most cardiologists can recall individual patients with heart failure whose condition appeared to improve in sinus rhythm and regress when atrial fibrillation recurred. A large multicenter trial is being conducted to evaluate whether the benefits of sinus rhythm in patients with heart failure are sufficiently great to offset the risks of therapy with antiarrhythmic drugs. Better therapies are still needed, but no new drugs have reached the market.
Nonpharmacologic therapies for atrial fibrillation have advanced rapidly. Surgery to correct arrhythmia abolishes atrial fibrillation in more than 90 percent of patients in some series, presumably by interrupting paths for reentry. However, because of the morbidity associated with the procedure, it is largely reserved for patients who also require valvular or coronary-artery bypass surgery.
In 1997, Jais et al.3 showed both that paroxysmal atrial fibrillation was initiated in some patients by triggering foci in the sleeves of musculature extending along the pulmonary veins and that catheter ablation of these triggers could abolish fibrillation. Multiple triggering foci were common. Ablation was often effective for paroxysmal atrial fibrillation but usually failed in patients with chronic atrial fibrillation.
From studies in animals and in humans, a picture of disease progression has emerged. Triggering foci cause paroxysmal atrial fibrillation, but with progressive atrial disease, modification of ionic currents and structural changes, including fibrosis in the atria outside the pulmonary veins, promote reentry. Catheter-ablation procedures have evolved and have become more extensive, encircling the antra of all pulmonary veins (Figure 1) and often incorporating additional connecting lines of ablation lesions that are likely to interrupt potential reentry paths.4 Although there is controversy about the best location for placement of the lesion and the importance of preventing triggers, as compared with interrupting the substrate for reentry paths, it seems likely that current ablation procedures have an effect on both the triggering foci and the reentry substrate. Some triggers are clearly outside the veins, and some reentry paths probably involve the ostial regions of the pulmonary vein. At experienced centers, practitioners now report rates of success of 75 percent or more among patients with paroxysmal atrial fibrillation. However, among patients with chronic atrial fibrillation, atrial dilatation, or impaired ventricular function, lower success rates (60 percent or less) have been reported.
Figure 1. A Three-Dimensional Reconstruction of the Left Atrium and Pulmonary Veins Viewed from the Right Posterior Position.
The inset at the right shows the right inferior pulmonary veins as viewed from the inside of the atrium. Ablation lesions would typically be placed along the white dashed line to encircle the antrum of the veins.
In this issue of the Journal, Hsu et al.5 report the outcome of catheter ablation in a consecutive series of patients with heart failure and atrial fibrillation in whom therapy with antiarrhythmic drugs had failed. Ablation (with additional therapy with antiarrhythmic drugs in approximately 10 percent of patients) achieved sinus rhythm in 78 percent of patients during a mean follow-up period of one year. After ablation, left ventricular function convincingly improved, with the ejection fraction returning to normal in 72 percent of patients. Symptoms and exercise capacity also improved. It is interesting to note that ventricular function improved even in patients with previously good heart-rate control. That finding indicates either that the degree of heart-rate control was still overestimated, despite a 48-hour recording time, or that the irregularity of the rhythm itself contributed to depressed ventricular function in some patients.
It should be recognized that these patients may not be typical of the average patient with heart failure and atrial fibrillation. They were referred to a center that is widely known for work in ablation, perhaps at a time when referring physicians thought that atrial fibrillation in particular was contributing to the aggravation of heart failure or that rate control was especially difficult. Even so, such patients are probably common, since the effect of atrial fibrillation on heart failure and the importance of achieving rate control at rest and with exertion are often underappreciated.
These results are encouraging, but a cautious approach is warranted. Catheter ablation of atrial fibrillation is a relatively recent procedure that continues to evolve. The present study lacks a control group of patients with heart failure and confirmation of long-term maintenance of initial benefits. The findings are consonant, however, with the results of a nonrandomized cohort study by Pappone et al., which showed that 589 patients who were treated with ablation had lower rates of mortality and morbidity, including stroke and heart failure, than did a contemporaneous group of 582 patients with atrial fibrillation who were treated medically.4 Catheter ablation of atrial fibrillation is a technically challenging procedure. In the study by Hsu et al., approximately half of the patients underwent two ablation procedures because of early recurrences of arrhythmia. Although early recurrent arrhythmias can spontaneously resolve with further maturation of the ablation lesions, waiting for spontaneous resolution may be problematic in patients with heart failure. The learning curve for the procedure and the potential risks are substantial. In the present series, major complications included stroke and cardiac tamponade. A large review recently reported symptomatic pulmonary-vein stenosis in approximately 4 percent of patients.6 Fatal atrial esophageal fistulae have only recently been recognized as a potential complication. Further technical improvements are needed, and more studies of safety and efficacy will be welcome. Whether anticoagulation should be discontinued, as was done in this trial, requires further evaluation, since asymptomatic recurrences are common in some studies.
The present study provides further evidence that some patients with atrial fibrillation and heart failure stand to benefit from restoration of sinus rhythm if that goal can be achieved without adverse effects of treatment. Further improvements are needed to make ablation easier and safer before it will be available outside highly experienced centers. Five years from now, will ablation for rhythm control be a first line of therapy for atrial fibrillation? The development of antiarrhythmic drugs that act specifically on the atrial myocardium without causing ventricular proarrhythmia appears to be feasible. Catheter ablation is easier for rate control than for rhythm control. Creating heart block and implanting a permanent pacemaker provide regularization of the ventricular rate, and the use of biventricular pacemakers may prevent an adverse effect of right ventricular pacing on left ventricular function. As in all cases of cardiac disease, the best long-term hope lies with therapies that provide protection against atrial fibrillation by preventing the initial development of atrial fibrosis and remodeling.
Dr. William Stevenson reports having received consulting and lecture fees and grant support from Biosense Webster and lecture fees from CryoCath Technologies. Dr. Lynne Stevenson reports having received consulting fees and grant support from Medtronics.
Source Information
From the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston.
References
Stevenson WG, Stevenson LW. Atrial fibrillation in heart failure. N Engl J Med 1999;341:910-911.
Corley SD, Epstein AE, DiMarco JP, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation 2004;109:1509-1513.
Jais P, Haissaguerre M, Shah DC, et al. A focal source of atrial fibrillation treated by discrete radiofreqency ablation. Circulation 1997;95:572-576.
Pappone C, Rosanio S, Augello G, et al. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol 2003;42:185-197.
Hsu L-F, Ja?s P, Sanders P, et al. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004;351:2373-2383.
Saad EB, Rossillo A, Saad CP, et al. Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation: functional characterization, evolution, and influence of the ablation strategy. Circulation 2003;108:3102-3107.(William G. Stevenson, M.D)