Epidemiological considerations and extension of the problem.
Atrial fibrillation and heart failure are recognised as the new two major epidemics of cardiovascular disease in the 21st century. According to longitudinal data, the prevalence of atrial fibrillation is approximately 1% and the incidence 0.2%, annually. Similarly, manifest heart failure affects at least 1-2% of the general population with one to five new cases diagnosed every 1000 persons, yearly. Both the prevalence and incidence of atrial fibrillation and heart failure increase with age, which, owing to the progressive ageing of the population and the growing proportion of elderly individuals, greatly accounts for the projected further increase of these two conditions in the near future.
Atrial fibrillation and heart failure are closely linked. Prof G. Steinbeck, from Munich - Germany, reported that in the AF-NET German Registry, heart failure coexists in about one third of the patients with atrial fibrillation (in 24% of those with paroxysmal, 41% of those with persistent, and 45.5% of those with permanent atrial fibrillation). Moreover, according to Framingham data, new-onset heart failure develops in another one third of patients during a 10-year period. Likewise, in patients with heart failure, atrial fibrillation is frequently present in 13% to 27% of cases, and “ex novo” atrial fibrillation is observed in 5.4% of subjects each year. The more severe heart failure is, the higher is the prevalence of atrial fibrillation (from 10% in NYHA functional class I-II to almost 50% in NYHA class functional IV). Interestingly, individuals with atrial fibrillation or heart failure, who subsequently develop the other condition, often have a clinical and haemodynamic deterioration, with significantly worsening of quality of life, reduction of maximum exercise performance, increased risk of thromboembolism, and increased mortality.
Mechanisms responsible for the coexistence of atrial fibrillation and heart failure
Several mechanisms may explain the coexistence of atrial fibrillation and heart failure, Prof M. Allessie, from Maastricht - The Netherlands, said. For example, atrial fibrillation with rapid ventricular response can lead to dilated cardiomyopathy, through myocardial ischaemia, calcium regulation abnormalities, or extracellular matrix remodeling. In addition, the loss of atrial transport and the irregularity of ventricular rhythm may predispose to heart failure by causing a fall in cardiac output. Conversely, heart failure can precipitate atrial fibrillation by inducing loss of myocardial mass, atrial dilatation, fibrosis, slowing of conduction, and dispersion of refractory periods. In a study conducted in 20 patients with dilated atria and operated on for mitral valve disease, the Maastricht group found that the following changes are potential mechanisms for the propensity to atrial fibrillation in patients with heart failure: longitudinal dissociation of pectinate muscles, narrow fibrillation waves with multiple sites of epicardial breakthrough, and lateral excitation.
Management of atrial fibrillation in patients with heart failure
At present, we do not know which strategy, between rhythm control and rate control, is better in patients with heart failure who develop atrial fibrillation. Indeed, the number of patients with heart failure that have been included in the randomised controlled trial of rhythm control versus rate control is too limited and we have to wait for the results of the ongoing AF-CHF trial (1378 patients enrolled by June 2006) before drawing any definitive conclusion in this regard. In the meanwhile, according to Prof D. Roy, from Toronto – Canada, an initial attempt at maintaining sinus rhythm is justified in heart failure patients whose atrial fibrillation onset is associated with severe hemodynamic deterioration. The cornerstone of anti-arrhythmic therapy in these patients is amiodarone, or dofetilide, whereas class I anti-arrhythmic agents are contraindicated. On the contrary, when onset of atrial fibrillation is not clearly associated with symptoms worsening, a rate control strategy with AV node depressant drugs or “ablate and pace” therapy may be an appropriate option, according to AFFIRM results. As far as regards anticoagulation, warfarin, with an INR target of 2 to 3, should be prescribed to all patients with atrial fibrillation and heart failure. In particular, anticoagulation should be continued even if sinus rhythm is restored.
Role of transcatheter ablation of atrial fibrillation
When antiarrhythmic drugs are ineffective and patients remain highly symptomatic, transcatheter ablation of atrial fibrillation in the left atrium may be a valuable alternative. Prof P. Jaïs and coworkers, from Bordeaux – France, have reported promising results to this regard. They have performed radiofrequency ablation in 86 patients with heart failure, by isolating all 4 pulmonary veins and by creating linear lesions on the roof of the left atrium and at the level of the mitral isthmus. During a mean follow-up of 14 months, 81% of patients remained in sinus rhythm (73% without antiarrhythmic drugs), although 48% of them required a redo procedure to reach this goal. The LV EF increased by 21%, as average, and most patients benefited from the ablative therapy with a significant improvement in quality of life and exercise capacity. More recently, Marchlinski and colleagues have shown similar results in 67 patients with LV EF 50% and well controlled ventricular rate (< 90 bpm): increase of average LV EF from 44% at baseline to 57% after ablation.
Role of non-antiarrhythmic drugs in patients with atrial fibrillation and heart failure
In the last years, some non-antiarrhythmic drugs, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone antagonists, and statins, have shown to be effective in preventing atrial fibrillation, especially in patients with systolic, but also in patients with diastolic left ventricular dysfunction. The action of these drugs seems to be multifactorial, as outlined by Prof J. Camm, from London – UK, and due to their antifibrotic, anti-inflammatory, and antiapoptotic effects. In particular, the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers seems to be associated with a significant reduction of new-onset and recurrent atrial fibrillation (more than 20%), when compared to placebo. However, these data essentially come from retrospective and/or post-hoc analysis. Therefore, further large prospective randomised trials are needed to confirm them. Three of these trials, ACTIVE, ANTI-PAF, and GISSI-AF, are ongoing and their results are expected in the near future.
Conclusion
Atrial fibrillation and heart failure are two conditions that often coexist in clinical practice. Current therapeutic strategy based on the use of conventional antiarrhythmic drugs is scarcely effective. Transcatheter ablation of atrial fibrillation and the use of non-antiarrhythmic drugs are promising alternatives. However, in the future novel therapies aimed at preventing or reducing atrial electrical and structural remodelling, as well as the development of atrial-selective antiarrhythmic agents are highly desirable.