Keywords
INTRODUCTION
The REVERSE (REgistro sobre la cardioVERSión en España [Spanish Cardioversion Registry]) study was undertaken with the aim of recording the clinical characteristics of patients with atrial fibrillation (AF) referred for cardioversion in Spain-no sufficiently large, specific, multi-center registries exist that describe the use of cardioversion in real life in this country.
The AFFIRM1,2 and RACE3 studies concluded that the strategy of controlling the heart rhythm does not reduce mortality/morbidity more than the control of the heart rate. Knowing the characteristics of patients referred for cardioversion in Spain would be of great interest when extrapolating results of other studies to our population. The aim of the present analysis was therefore to describe the characteristics and clinical management of Spanish patients with AF referred for elective cardioversion, and to compare the findings with the results of the AFFIRM and RACE studies.
METHODS
In this study, patients with AF referred for elective cardioversion at 96 Spanish hospitals between 1 February and 30 June 2004 were prospectively and consecutively included in our registry. The requirements for inclusion demanded patients be >18 years of age, to have persistent AF (of at least seven days duration), to show no evidence of precipitating factors, and that they be considered candidates for pharmacological or electrical cardioversion (ECV). The results of an echocardiogram performed in the 6 months prior to cardioversion were requested. Patients with more than mild valve dysfunction or stenosis of any degree were considered to have valve disease. Isolated AF was defined as that seen in patients <60 years of age without high blood pressure or cardiopulmonary disease.4 The REVERSE registry requires a follow-up of one year after ECV in patients without structural heart disease.
Statistical Analysis
Qualitative variables were expressed in terms of percentages; differences were analyzed using the c2 test. Quantitative variables were expressed as means (standard deviations); differences were analyzed using the Student t test. Patient clinical and echocardiographic information was compared with published data recorded by the AFFIRM and RACE studies.1-3 Significance was set at P<.05. All calculations were made using SPSS 12.0 software.
RESULTS
The present study involved 1515 patients with persistent AF, all of whom were referred for cardioversion; Table 1 shows their clinical and echocardiographic characteristics. Some 20% had previously received ECV treatment. Some 51% had structural heart disease (including moderate or more severe left ventricular hypertrophy). Isolated AF was seen in 10% of patients.
Oral anticoagulation was the most common anticoagulation strategy used during the cardioversion period (employed in 55% of cases); this therapy was provided for at least three weeks prior to, and 1 month after, cardioversion. Some 31% of patients received chronic anticoagulation therapy. Transesophageal echocardiography (TEE) was rarely used (8%). Only 4% of patients received low molecular weight heparins, and only 2% were treated using other strategies.
A total of 752 (50%) patients received some type I or III Vaughan-Williams anti-arrhythmic drug prior to undergoing ECV; the most used was amiodarone (40%), followed by flecainide/propafenone (7%) and other drugs (3%). Among those patients who had undergone a previous ECV there was a tendency to more commonly prescribe anti-arrhythmic drugs (53% were thus treated compared to 48% of those who had undergone no prior ECV; P=.10). Some 53% received angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARA-II).
One hundred and sixty patients (21%) were pharmacologically reverted to sinus rhythm (SR); 1355 were therefore subjected to ECV. Among the latter, 87% were released with SR having been recovered. Taking into account both pharmacological and electrical cardioversions, stable SR was achieved in 88% of the present patients.
A comparison was made between the clinical and echocardiographic characteristics of the REVERSE, the AFFIRM, and the RACE study patients (Table 1). Compared to the AFFIRM study subjects, the present patients were younger (63[11] years compared to 69.7[9] years; P<.0001) and the prevalence of high blood pressure, diabetes, pulmonary disease, ischemic heart disease and previous embolisms among them was lower. In addition, conserved systolic function was more prevalent, the size of the left atrium was slightly greater, and the sample included patients with AF of longer duration. Compared to the RACE subjects, the present patients were younger (63[11] years compared to 68[8] years; P<.0001), and the prevalence of prior ischemic heart disease and embolisms among them was lower. However, high blood pressure and diabetes were somewhat more common. In addition, fewer of the REVERSE patients showed structural heart disease (51% compared to 79% in the RACE study); no statistical analysis was performed for this comparison since the criteria for reporting "heart disease" were not specified in the RACE study. The size of the left atrium was similar in both patient populations. The RACE study did not report left ventricular ejection fraction data, thus no comparisons can be made in this respect.
DISCUSSION
The present patients clearly had a less serious cardiovascular risk profile than the patients of the AFFIRM study, and an apparently less serious profile than the RACE patients. The AFFIRM study included patients with AF with a high risk of suffering embolism or death; it is therefore to be expected that their clinical profiles should be different to those of the present registry who were consecutive patients referred for cardioversion. The characteristics of the AFFIRM patients' AF were different since there was no requirement for treatment with ECV. In addition, 31% of the AFFIRM patients suffered paroxysmal AF (<48 h duration). From the point of view of clinical and AF characteristics, the former study is more comparable to the present since inclusion in the RACE study required ECV treatment and did not demand that patients were likely to suffer cardiovascular complications (the patients were therefore more representative of the cardioversion candidate population). Although the prevalence of high blood pressure and diabetes was greater among the RACE patients, given the significant differences in the prevalence of prior embolisms and their mean age (the two most important factors in embololic risk),5 the REVERSE patients appear to be at lower risk of embolisms and other cardiovascular complications, bearing in mind the differences in the prevalence of ischemic heart disease and structural heart disease. We believe that the differences in clinical characteristics are in part due to these studies having influenced clinical practice in terms of a more strict selection of patients who are candidates for cardioversion. Hence, the extrapolation of their results to patients in the Spanish clinical setting should be performed with care.
The strategy of providing anticoagulation therapy for 3-4 weeks before and for at least 4 weeks after cardioversion, is preferred by Spanish cardiologists. The scant use of TEE is justified since, although it shortens the time between clinical decision-making and ECV, it provides little clinical benefit,6 especially since nowadays anticoagulation treatment is maintained over a long period.
Half of the present patients referred for cardioversion were receiving anti-arrhythmic treatment with type I or III Vaughan-Williams drugs. This strategy can be useful for the prophylaxis of immediate recurrences and recurrences in the first days after cardioversion, and it can help in achieving SR before ECV (as seen in 21% of the present patients). The ESC/AHA/ACC7 clinical practice guidelines on AF attach a grade IIa recommendation (evidence level B) to anti-arrhythmia treatment prior to cardioversion. It may also be more justified in patients who have undergone previous ECV - a criterion that appears to be used in Spain.
The large number of patients involved in the present study, and the participation of hospitals providing different levels of assistance, suggest the REVERSE registry reliably reflects clinical practice surrounding cardioversion in Spain.
PARTICIPATING RESEARCHERS AND CENTERS
Ordered by the number of patients enrolled:
L. Pérez; H. Juan Canalejo, A Coruña.
A. Hernández-Madrid; H. Ramón y Cajal, Madrid.
X. Sabaté; H. de Bellvitge, L'Hospitalet de Llobregat, Barcelona.
A. Medina; H. Dr. Negrín, Las Palmas de Gran Canaria.
L. Mont; H. Clínic, Barcelona.
A. Berruezo; H.U. Puerta del Mar, Cádiz.
A. Moya; H.G.U. Vall d'Hebron, Barcelona.
J.L. Martínez Sande; H.C. Universitario, Santiago de Compostela, A Coruña.
A. Pastor; H.U. de Getafe, Madrid.
A. Grande; H. Severo Ochoa, Leganés, Madrid.
J. Villacastín; H.C.U. San Carlos, Madrid.
J.G. Martínez; H.G.U. de Alicante, Alicante.
L. Azocar; H. de Sant Pau, Barcelona.
E. Castellanos; H. Virgen de la Salud de Toledo, Toledo.
N. Pachón; H.U. Central de Asturias, Oviedo, Asturias.
F. Crespo; H. Xeral Calde, Lugo.
F. Freire; H. de Palamós, Girona.
J. González Ruiz; H. de Galdácano, Vizcaya. J.F. García Sacristán; H. General de Albacete.
J. Benezet; H. Nuestra Señora de Alarcos, Ciudad Real.
T. Ripio; H. Son Llatzer, Palma de Mallorca.
A. Asso; H. Miguel Servet, Zaragoza.
X. Beiras; H. Xeral Cies, Vigo, Pontevedra.
R. Barba; H.J. Ramón Jiménez, Huelva.
F. Redondo; H. Cristal Piñor, Orense.
J.R. Casariego; H. Montecelo, Pontevedra.
L. Tercedor; H. Virgen de las Nieves, Granada.
J. Delso; H. Creu Roja, Barcelona.
R. Pavón; H.U. de Valme, Sevilla.
J. Ormaetxe; H. de Basurto, Bilbao, Vizcaya.
L. García Riesco; H. del Riotinto, Huelva.
P. Gil; H. Txagorritxu, Vitoria.
V. Palanca; H. General Universitario, Valencia.
A. Pedrote; H.U. Virgen del Rocío, Sevilla.
M. González; H.U. La Paz, Madrid.
C. Expósito; H. Son Dureta, Palma de Mallorca.
C. Ledesma; H.U. de Salamanca.
E. González; H. General de Jerez, Jerez de la Frontera, Cádiz.
B. Herreros; H. Río Hortega, Valladolid.
C. Romero; H. de Sant Boi de Llobregat, Barcelona.
R. Canals; H. Comarcal de Mollet, Barcelona.
J.R. Carmona; H. de Navarra, Pamplona, Navarra.
O. Medina; H.U. Insular de Gran Canaria, Las Palmas.
J. Olagüe; H.U. La Fe, Valencia.
P. Carrillo; H.U. de San Juan de Alicante, Alicante.
I. García-Bolao; C.U. de Navarra, Pamplona, Navarra.
F. Mazuelos; H. Reina Sofía, Córdoba.
L. Guillamon; H. General de Catalunya, Sant Cugat del Vallés, Barcelona.
J. Arana; H. de Cruces, Baracaldo, Vizcaya.
I. Duran; H.U. Sant Joan de Reus, Tarragona.
J. Pelegrin; C.U. Lozano Blesa, Zaragoza.
J. Muñoz; H.U. Ciudad de Jaén, Jaén.
J. Rubio; H.U. de Valladolid.
J.M. González; H. de León.
A. Moleiro; H. General de Vic, Barcelona.
M. Anton; H. Torrecárdenas, Almería.
A. Ardiaca; H. Arnau de Vilanova, Lleida.
I. Lechuga; H. Verge de la Cinta, Tortosa, Taragona.
P. García; H. General Santa María de Rosell, Cartagena, Murcia.
A.G. Alberola; H.U. Virgen de La Arrixaca, Murcia.
A. Rodríguez; H.C.U. de Canarias, La Laguna, Tenerife.
N. Batalla; H. Sagrat Cor, Barcelona.
M. López; H.G.U. Gregorio Marañón, Madrid.
E. Sanz; H.U. Joan XXIII, Tarragona.
F. del Campo; H. Virgen de la Concha, Zamora.
I. Fernández Lozano; C. Puerta de Hierro, Madrid.
J. Sánchez; H. Rafael Méndez, Lorca, Murcia.
F. López; H. de la Ribera, Alzira, Valencia.
S. Castillo; H. Germans Trias i Pujol, Badalona, Barcelona.
J. de Miguel; H. de Terrassa, Barcelona.
J.G. Reverte; H.G.U. de Murcia.
J. Alzueta; H.C.U. Vigen de la Victoria, Málaga.
F. Ruiz; H. Costa del Sol, Marbella, Málaga.
I. Romeo; H. d'Igualada, Barcelona.
J.A. Ruiz; H.G.U. Morales Meseguer, Murcia.
G. Vázquez; H. de Sant Jaume, Calella, Barcelona.
J. Domínguez; H. General Yagüe, Burgos.
M. López; H. 12 de Octubre, Madrid.
G. Fernández; H.U. Infanta Cristina, Badajoz. M.L. Moro; H. de Mérida, Badajoz.
M. Pavón; H.U. Virgen Macarena, Sevilla.
M. Pujol; H. de Viladecans, Barcelona.
G. Vázquez; H. Comarcal de La Selva, Blanes, Girona. J.J. Cortina; H. General de Segovia.
J. Vega; H. San Pedro de Alcántara, Cáceres.
J. Vara; H. San Juan de Dios, León.
J. Castro; H.G.U. de Guadalajara.
A. Navarro; H. General de Castellón.
A. Criado; H. de Móstoles, Madrid.
F. Martínez; H. Los Arcos, San Javier, Murcia.
C.A. Berrocal, H. General Río Carrión, Palencia.
A. Descalzi; H. Comarcal Alt Penedés, Vilafranca del Penedés, Barcelona.
L. Martínez; H.U. de la Princesa, Madrid.
F. Planas; H. de Badalona, Barcelona.
E. Cabello; H. Virgen del Puerto, Plasencia, Cáceres.
J. Viñas; H. General Virgen de la Luz, Cuenca.
A full list of the researchers and hospitals involved in the REVERSE study is provided at the end of this paper.
Correspondence:
Dr. J.M. Alegret,
Sección de Cardiología, Hospital Universitari de Sant Joan de Reus, Sant Joan s/n, 43002 Reus, Tarragona, Spain
E-mail: txalegret@hotmail.com
Received 27 April, 2007.
Accepted for publication 2 November, 2007.