Effects of sinus rhythm restoration in patients with persistent atrial fibrillation: a clinical, echocardiographic and hormonal study

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Abstract

The hemodynamic consequences of atrial fibrillation (AF) may lead to impairment of the left ventricular function and a reduction in exercise capacity. Studies on mechanical and neurohormonal remodelling in patients with AF are becoming increasingly important. The results could possibly enhance treatment strategies of these patients. The aim of this study was to assess changes in exercise capacity, echocardiographic findings and plasma atrial natriuretic peptide (ANP) concentrations in patients with non-rheumatic persistent AF, before and 30 days after successful cardioversion. Methods: We attempted cardioversion in 42 consecutive patients, aged 58±8 years, with persistent non-valvular AF of duration 7.1±7.1 months. They underwent echocardiography examination and submaximal exercise testing 24 h before and 30 days after cardioversion. Exercise capacity was determined during symptom-limited exercise testing, according to a modified Bruce protocol with peak VO2 analysis. Plasma samples of ANP were obtained at rest: before, the day after, and 30 days after cardioversion therapy, and were prepared by refrigerated centrifugation and stored until radioimmunoassay. The control study group, without AF, comprised of 11 subjects. Results: Cardioversion was successful in 35 patients. However, in six of the 35 patients, AF reappeared within 1 month. There were no statistical differences before cardioversion in exercise tolerance and ejection fraction of left ventricle between the group with successful cardioversion and the group with unsuccessful cardioversion or with recurrence of AF. On the 30th day after cardioversion we recorded a significant increase in exercise tolerance: duration of exercise 13.7±3.2 versus 9.5±3.4 min, (P<0.05); peak oxygen consumption 32.2±3.6 versus 19.85±3.5 ml/min per kg, (P<0.05); and ejection fraction of left ventricle 58.6±9.4 versus 52.7±10.2% (P<0.05); in the sinus rhythm group. There was no significant improvement observed in the AF group. The mean baseline ANP level was 58.5±15.7 pg/ml in the study group and 34.3±10.2 pg/ml in the control group (P<0.01). The successful therapy reduced significantly the pretreatment mean plasma ANP concentration from 58.5±15.7 to 31.4±15.0 pg/ml, (P<0.01); the day after cardioversion, in the group of 35 patients. It remained stable for the next 30 days (36.9±15.2 pg/ml) in the group of 29 patients who remained in sinus rhythm, and increased to 53.4±16.4 pg/ml in the group of six patients who had recurrence of AF. Plasma ANP did not change in the group of seven patients with unsuccessful cardioversion. Conclusions: The restoration of sinus rhythm in patients with persistent AF was associated with a significant improvement in cardiac performance and exercise tolerance 1 month after cardioversion. Such improvement was not observed in the group with unsuccessful cardioversion or with AF recurrence. The plasma ANP concentration in patients with AF was significantly reduced after successful cardioversion and remained stable for a period of 30 days.

Introduction

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practise. The prevalence is estimated at 0.4% of the general population and greater than 6% in patients over 80 years [1]. The overall incidence of AF is likely to rise in the next decades as the elderly population is increasing in industrialised countries. AF is an independent predictor of increased mortality and morbidity and is associated with higher risk of thromboembolic events. Loss of atrial systolic function and a fast, irregular, ventricular response result in impairment of hemodynamic function [2]. In several cases the hemodynamic effects can result in heart failure [3]. On the other hand heart failure is an important risk factor for the development of AF and associated with AF has a worse prognosis than heart failure without AF [4].

In clinical practice, AF remains the most difficult arrhythmia to treat. The criteria to select patients for the different therapeutic options are still a matter of debate. However, the symptoms of AF such as palpitations, a reduced exercise tolerance and impact on quality of life provide a clear reason to consider early restoration and maintenance of sinus rhythm.

Electrical remodelling (shortening of atrial refractoriness) develops within the first days of AF [5]. Tachycardia-induced structural and hormonal remodelling takes place over a different time period and probably correlates with the duration of AF. The electrical, mechanical and hormonal remodelling are completely reversible after successful cardioversion of short term persistent AF but after prolonged duration of AF recovery from contractile dysfunction, due to intracellular calcium overload and ‘atrial stunning’, may take several weeks to months and is not well-defined [6], [7], [8].

The purpose of our study was to assess changes in exercise capacity, echocardiographic findings and cardiac hormonal activity reflected by the evolution of atrial natriuretic peptide (ANP) level in patients with non-rheumatic persistent AF, just before and 30 days after cardioversion.

Section snippets

Methodology

We studied 42 patients who had a broad spectrum of underlying cardiac disease (Table 1) and were admitted for cardioversion of AF to normal sinus rhythm. The mean age of the study group was 58±8 years; 29% were women. The mean duration of AF was 7.1±7.1 consecutive months. The time of onset of AF was taken as the onset of symptoms or the first documentation of AF in asymptomatic patients. Twenty six (62%) out of 42 patients were in NYHA I–II classification, 16 (38%) patients were in NYHA III

Results

The mean age of study group was 58±8 years; 29% were women. The mean duration of AF was 7.1±7.1 consecutive months. Twenty six (62%) out of 42 patients were in NYHA I–II classification, 16 (38%) patients were in NYHA III classification.

Thirty days after cardioversion only two (5%) patients were in the third functional class according to the NYHA classification. Thirty-five out of the 42 patients were successfully cardioverted to sinus rhythm. Thirty days after cardioversion, 29 patients

Discussion

The major consequences of AF may be subdivided as electrophysiological, hemodynamic, hormonal and thromboembolic. The impact of AF on both exercise and cardiac resting output has been examined in a number of studies [11], [12]. The loss of atrial systolic function results in a reduction in stroke volume, leading to lower cardiac output and increased atrial stasis. The contribution of atrial systolic function (‘atrial kick’) is particularly important with increasing age, due to progressive

Conclusions and clinical implications

Our data confirm that successful cardioversion of persistent AF improves hemodynamic measures of cardiac performance, increases exercise capacity, leads to normalisation of plasma ANP levels and prevents heart cavity enlargement. Restoration of sinus rhythm should be considered in previously non-cardioverted patients, under 60, with persistent AF.

Acknowledgements

We would like to thank Fergus Mahon and Marek Strzelecki for their help.

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