JOURNAL OF WOMEN’S HEALTH Volume 24, Number 6, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/jwh.2014.5014
Gender Differences in Patients with Atrial Fibrillation Undergoing Electrical Cardioversion Josep M. Alegret, MD, PhD,1 Xavier Vin˜olas, MD, PhD,2 Antoni Martı´nez-Rubio, MD, PhD,3 Alonso Pedrote, MD,4 Xulio Beiras, MD, PhD,5 Jesu´s F. Garcı´a-Sacrista´n, MD,6 Francisco Crespo-Mancebo, MD,7 and Francisco Ruiz-Mateas, MD 8
Abstract
Background: Current recommendations on the rhythm control strategy for treatment of atrial fibrillation (AF) are more restrictive than a decade ago. Gender may play a role in decisions on the management of AF, including application of electrical cardioversion. Methods: We analyzed clinical characteristics by gender in patients participating in the observational survey about stable patients underlying cardioversion in Spain (CARDIOVERSE) study (n = 915), a survey of the practice of electrical cardioversion in 67 Spanish hospitals. We compared these data with those from a previous survey of electrical cardioversion in Spain (REVERSE study) performed 8 years previously. Results: Patients undergoing electrical cardioversion were mainly men (76%). This finding was observed in all age groups, independently of symptoms. Men were younger (62 – 10 years vs. 69 – 9 years; p < 0.001), more frequently asymptomatic and had a lower prevalence of hypertension and a lower stroke risk. Among asymptomatic patients, the predominance of men was especially evident in older age groups ( < 65 years, men 76%, women 24%; ‡ 65 years, men 92%, women 8% ( p < 0.001). Compared with the REVERSE study, we observed a decrease in the percentage of women among patients undergoing electrical cardioversion (37% REVERSE vs. 24% CARDIOVERSE; p < 0.001), mainly in older than 65 years. Conclusions: Our results support the hypothesis that gender is a determinant in decisions on the most appropriate strategy for managing AF. We observed a decrease in the percentage of women undergoing electrical cardioversion during the last decade, especially in older asymptomatic patients. Introduction
T
he atrial fibrillation follow-up investigation of rhythm management (AFFIRM) and rate versus electrical cardioversion for permanent atrial fibrillation study (RACE) trials1,2 demonstrated no differences in morbidity and mortality when comparing rate control strategies with rhythm control strategies in patients with atrial fibrillation (AF). The results of both trials have influenced guidelines3,4 and clinical practice, leading to stricter criteria for rhythm control strategies and less frequent use of electrical cardioversion.5,6 Gender differences have been observed in the management of ischemic heart disease, with more conservative management reported in women.7,8 Previous studies also revealed gender
differences in the clinical characteristics of patients with AF and in the management of AF. Thus, women with AF are older, more symptomatic, and seem to be at a higher risk of stroke.9–12 Data from the Euro Heart Survey on Atrial Fibrillation suggested less frequent use of rhythm control strategies in women.13 Patients treated with cardioversion represent persistent AF patients treated with rhythm control strategy. In the present study, we investigated the possible influence of gender in decisions on the treatment of patients with AF during the last decade. We analyzed gender-related clinical characteristics in the observational survey about stable patients underlying cardioversion in Spain (CARDIOVERSE) study, a Spanish survey of patients undergoing electrical cardioversion. We also compared the gender distribution in
1
Grup de Recerca Cardiovascular, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain. Hospital de la Sta. Creu i St. Pau, Barcelona, Spain. Hospital Universitari Parc Taulı´, Sabadell, Spain. 4 Hospital Universitario Virgen del Rocı´o, Sevilla, Spain. 5 Complejo Hospitalario Universitario de Vigo, Vigo, Spain. 6 Hospital General de Albacete, Albacete, Spain. 7 Hospital Lucus Augusti, Lugo, Spain. 8 Hospital Costa del Sol, Marbella, Spain. 2 3
466
UNDERUSE OF ELECTRICAL CARDIOVERSION IN WOMEN
the CARDIOVERSE study with that of the REVERSE study,14 a survey of electrical cardioversion in Spain performed 8 years previously. Methods
The CARDIOVERSE study was designed to monitor the clinical practice of elective electrical cardioversion in Spain
467
by prospectively recording all patients with persistent AF who underwent the procedure between February 1 and June 30, 2012, in 67 Spanish hospitals (Supplementary Appendix S1; Supplementary Data are available online at www .liebertpub.com/jwh). Nine hundred and fifteen consecutive patients were included. The inclusion criteria were age > 18 years, duration of AF > 7 days, and absence of precipitating conditions (e.g., hyperthyroidism, fever, cardiac surgery, and
Table 1. Characteristics of 915 Patient Participants in the CARDIOVERSE Study Segregated by Gender
Age, years BMI, kg/m2 BSA, m2 LA, mm Indexed LA, mm/m2 LVEF, quantitative LVEF, qualitative, n (%) Normal ( ‡ 50%) Slightly depressed (41%–49%) Moderately (31%–40%) Severely ( £ 30%) Hypertension, n (%) Diabetes mellitus, n (%) LV hypertrophy, n (%) Pulmonary disease, n (%) Valvulopathy, n (%) Congestive heart failure, n (%) NYHA, n (%) Class 1 Class 2 Class 3 Class 4 Previous electrical CV, n (%) CHADS2, n (%) Low risk (score = 0) Medium risk (score = 1) High risk (score ‡ 2) CHA2DS2VASc, n (%) Low risk (score = 0) Low-medium risk (score = 1) Medium-high risk (score ‡ 2) HAS-BLED, n (%) Low-medium risk (score < 3) High risk (score ‡ 3) Duration of AF, n (%) 8 days–1 month 1–3 months 3–12 months > 12 months Unknown Symptoms related to AF, n (%) (EHRA scale) 1. No symptoms 2. Mild (normal daily activity not affected) 3. Severe (normal daily activity affected) 4. Disabling (normal daily activity discontinued)
Men (n = 694)
Women (n = 221)
p
61.9 – 10.1 29.4 – 4.3 2.00 – 0.17 44.3 – 5.8 22.3 – 3.4 56.6 – 11.9
68.3 – 8.6 29.6 – 5.7 1.78 – 0.17 42.7 – 5.8 24.4 – 3.9 59 – 10.6
< 0.001 0.54 < 0.001 0.001 < 0.001 0.02
497 66 40 41 398 138 195 82 62 110
(77) (10) (6) (6) (57) (20) (30) (12) (30) (16)
174 14 12 6 149 37 45 7 44 47
(85) (7) (6) (3) (67) (17) (22) (3) (65) (21)
153 416 118 7 121
(22) (60) (17) (1) (17)
37 137 38 9 41
(17) (62) (17) (4) (18)
0.09
0.009 0.33 0.02 < 0.001 < 0.001 0.06 0.51
0.75
209 (30) 284 (41) 201 (29)
43 (19) 83 (38) 95 (43)
< 0.001
142 (20) 214 (31) 338 (49)
0 (0) 19 (9) 202 (91)
< 0.001
641 (92) 53 (8)
206 (93) 15 (7)
0.67
31 187 253 118 105
(5) (27) (37) (17) (19)
15 53 84 38 31
(7) (24) (38) (17) (14)
0.62
313 319 50 6
(46) (46) (7) (1)
57 130 26 6
(26) (59) (12) (3)
< 0.001
Values represent mean – standard deviation or n (%). AF, atrial fibrillation; BMI, body mass index; BSA, body surface area; CARDIOVERSE, observational survey about stable patients underlying cardioversion in Spain; CHADS2, hypertension, age ‡ 75 years, diabetes mellitus, stroke; CHA2DS2VASc, congestive heart failure, hypertension, age ‡ 75 years, diabetes mellitus, stroke, vascular disease, age 65–74 years, sex category; CV, cardioversion; EHRA, European Heart Rhythm Association; HAS-BLED, hypertension, abnormal renal, liver function, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly; LA, left atrium; LVEF, left ventricle ejection fraction; NYHA, New York Heart Association.
468
ALEGRET ET AL.
pericarditis). Patients were followed for 1 year (visits at 1, 3, 6, and 12 months after cardioversion) We analyzed the clinical characteristics of participants by gender and compared the results with those obtained in the REVERSE study, a survey on electrical cardioversion carried out in 96 Spanish hospitals by our group in between January 1 and June 30, 2004, with the same inclusion criteria.14,15 One thousand five hundred and fifteen patients were included. In that survey, the one-year follow-up was only applied to patients who did not have structural heart disease. Statistical analyses
Continuous variables are expressed as mean – standard deviation, and comparisons between groups were made using the t test for independent values. Categorical variables are expressed as percentages and were analyzed using the chisquared test. Differences were considered statistically significant if p < 0.05. The statistical analysis was performed using SPSS statistical software package (version 18). The study was approved by the institutional review boards (clinical ethics committee) of each participating hospital. Written informed consent was obtained from all the patients who participated in this study. Results
Patients were predominantly men (76%). Table 1 presents the clinical characteristics of patients segregated by gender. The predominance of men was observed in all age groups, although the percentage of women increased with age (Fig. 1). The percentage of patients who had previously undergone electrical cardioversion was similar for both men and women. Women were older and had a lower prevalence of left ventricular hypertrophy, and left ventricular dysfunction and a higher prevalence of hypertension and risk of stroke by hypertension, age ‡ 75 years, diabetes mellitus, stroke (CHADS2) and congestive heart failure, hypertension, age ‡ 75 years, diabetes mellitus, stroke, vascular disease, age 65– 74 years, sex category (CHA2DS2VASc) scores. Men were predominant in symptomatic (69%) as well asymptomatic patients (85%). The predominance of men in asymptomatic
FIG. 1. Distribution of men and women segregated depending on the age range.
FIG. 2. Comparison of the proportion of women between the survey about cardioversion in Spain (REVERSE) and observational survey about stable patients underlying cardioversion in Spain (CARDIOVERSE) studies depending on the age range. patients was especially evident in older patients ( < 65 years, men 76% vs. women 24%; ‡ 65 years, men 92% vs. women 8%; p < 0.001). With respect to the REVERSE study, we noted a decrease in the proportion of women undergoing cardioversion (CARDIOVERSE 24% vs. REVERSE 37%; p < 0.001) in all age groups. This decrease was more evident in patients > 65 years old (Fig. 2). Women participating in the REVERSE study had higher left atrial size, higher left ventricular ejection fraction and better functional class (Table 2).
Table 2. Differences in the Characteristics of Women Included in the REVERSE and CARDIOVERSE Studies REVERSE CARDIOVERSE n = 557 n = 221 Age, years Age ‡ 70 years BMI, kg/m2 BSA, m2 LA, mm Indexed LA, mm/m2 LVEF, quantitative Normal LVEF ( ‡ 50%), n (%) Hypertension, n (%) Diabetes mellitus, n (%) Pulmonary disease, n (%) NYHA ‡ II, n (%) Previous electrical CV, n (%) CHADS2 ‡ 2, n (%) Duration of AF > 12 months, n (%)
p
67.7 – 9.8 270 (49) 29.1 – 5.4 1.79 – 0.17 44.4 – 6.2 25 – 4.0 61.4 – 9.6 511 (92)
68.3 – 8.6 99 (45) 29.6 – 5.7 1.78 – 0.17 42.7 – 5.8 24.4 – 3.9 59 – 10.6 174 (85)
0.43 0.35 0.25 0.46 < 0.001 0.05 0.002 < 0.001
344 (62) 101 (18)
149 (67) 37 (17)
0.14 0.65
35 (6)
7 (3)
0.03
325 (58) 104 (19)
184 (83) 41 (18)
< 0.001 0.97
201 (36) 48 (9)
95 (43) 38 (17)
0.07 0.006
Values represent mean – standard deviation or n (%). REVERSE, survey about cardioversion in Spain.
UNDERUSE OF ELECTRICAL CARDIOVERSION IN WOMEN
We observed in both genders a similar rate of successful electrical cardioversion (men 92% vs. women 94%; p = 0.26), maintenance of sinus rhythm at one month (men 58% vs. women 57%; p = 0.91) and at one year (men 32% vs. women 29%; p = 0.48). Discussion
Fewer women than men underwent electrical cardioversion. This difference was observed in all the age groups and was independent of the presence of AF symptoms. The greatest difference was in asymptomatic patients in the oldest quartile. In the last decade, fewer women underwent electrical cardioversion, especially in the oldest age group. Our results suggest that electrical cardioversion is underused in women and that gender is taken into account when deciding on the AF strategy to be applied. Current guidelines recommend stricter criteria for the rhythm control strategy and suggest using electrical cardioversion less frequently. Patients undergoing electrical cardioversion today are more symptomatic and with a higher cardiovascular disease burden.6 We have observed similar findings in women, comparing their clinical characteristics at REVERSE and CARDIOVERSE studies. It is difficult to speculate about the reasons for variations in use of electrical cardioversion depending on gender. Differences could be due, in part, to a lower prevalence of symptomatic women in the population. However, epidemiological data on patients recently diagnosed with AF showed that women were more likely to have symptomatic AF than men.9 In addition, the percentage of men was higher in both symptomatic patients and in asymptomatic patients, and men predominated in all the age groups. The poorer prognosis of women treated with a rhythm control strategy described in the RACE study could have some influence on the decrease in the percentage of women undergoing electrical cardioversion in the last decade.16 Moreover, a higher risk of complications has been described in women undergoing AF ablation17,18 a technique also implicated in the rhythm control strategy. We cannot conclude that the lower use of electrical cardioversion in women was based solely on the cardiologist decision. In the usual discussion with the patient about the different treatment options, perhaps women are less predisposed to be treated with rhythm control strategy. Further studies are needed to explore the possible gender differences in the perceived risk of cardioversion and stroke. The main limitation of our study was that we analyzed a group of patients undergoing electrical cardioversion but not the management of patients diagnosed with AF in the population. Previous European epidemiological studies showed an increasing prevalence of AF with aging and higher AF prevalence and incidence in men than in women,9,18 although the total number of women with AF was higher due to the predominance of women in the oldest age groups. Recent data about the prevalence of AF in Spain show a similar overall prevalence in men and women,20 although this differed depending on the age group analyzed, with the percentage of women increasing steeply after 60 years. Taking into account the percentage of women in the different ranges of age analyzed in that study, our data clearly suggest a lower use of electrical cardioversion in all the range of age in women. We have observed in women undergoing electrical
469
cardioversion an increased risk of stroke risk evidenced by higher CHADS2/CHA2DS2VASc scores. This was due to a higher prevalence of hypertension and heart failure, but mainly to their older age, as seen in the increased prevalence of women when the age range increased. In treating AF, one of the ways to prevent stroke could be to prevent AF. Women are at higher risk of stroke, but perhaps are not treated as aggressively to achieve and maintain sinus rhythm, which could help to decrease stroke risk. The ongoing EAST study may clarify whether a strict rhythm control strategy can reduce the incidence of stroke.21 In conclusion, our results support the hypothesis that gender is a determinant in decisions on the most appropriate strategy for managing AF, independently of other clinical factors. We observed a decrease in the percentage of women undergoing electrical cardioversion during the last decade, especially in older asymptomatic patients. Acknowledgments
This study was funded by Bayer Health Care Spain. Author Disclosure Statement
No competing financial interests exist. References
1. Wyse DG, Waldo AL, DiMarco JP, et al.; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825–1833. 2. Van Gelder IC, Hagens VE, Bosker HA, et al. RateControl versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834–1840. 3. European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery; Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the management of atrial fibrillation: The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace 2010;12:1360–1420. 4. Wann LS, Curtis AB, January CT, et al. 2011 ACCF/AHA/ HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Heart Rhythm 2011;8:157–176. 5. Mason PK, Wood MA, Lake D, DiMarco JP. Influence of the randomized trials, AFFIRM and RACE, on the management of atrial fibrillation in two University Medical Centers. Am J Cardiol 2005;95:1248–1250. 6. Alegret JM, Vin˜olas X, Romero-Menor C, et al. Trends in the use of electrical cardioversion for atrial fibrillation: influence of major trials and guidelines on clinical practice. BMC Cardiovasc Disord 2012;12:42. 7. Ayanian JZ, Epstein AM. Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med 1991;325:221–225. 8. Vidal-Pe´rez R, Otero-Ravin˜a F, Go´mez Va´zquez J, et al.; Barbanza Investigators. Ischemic heart disease in women. Data from BARIHD study. Rev Esp Cardiol 2012;65:1056–1058.
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9. Humphries KH, Kerr CR, Connolly SJ, et al. New-onset atrial fibrillation: Sex differences in presentation, treatment, and outcome. Circulation 2001;103:2365–2370. 10. Heeringa J, Van Der Kuip DA, Hofman A, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: The Rotterdam study. Eur Heart J 2006;27:949–953. 11. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: A systematic review. Neurology 2007;69:546–554. 12. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns H. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation. Chest 2010;137:263–272. 13. Dagres N, Nieuwlaat R, Vardas PE, et al. Gender-related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe. A report from the Euro heart survey on atrial fibrillation. J Am Coll Cardiol 2007;49:572–577. 14. Alegret JM, Vin˜olas X, Sagrista´ J, et al. Clinical characteristics of patients with persistent atrial fibrillation referred for cardioversion: Spanish Cardioversion Registry (REVERSE). Rev Esp Cardiol 2008;61:630–634. 15. Alegret JM, Vin˜olas X, Sagrista´ J, et al.; REVERSE Study Investigators. Predictors of success and effect of biphasic energy on electrical cardioversion in patients with persistent atrial fibrillation. Europace 2007;9:942–946. 16. Rienstra M, Van Veldhuisen DJ, Hagens VE, et al. Genderrelated differences in rhythm control treatment in persistent atrial fibrillation: Data of the rate control versus electrical cardioversion (RACE) study. J Am Coll Cardiol 2005;46: 1298–1306.
ALEGRET ET AL.
17. Michowitz Y, Rahkovich M, Oral H, et al. Effects of sex on the incidence of cardiac tamponade after catheter ablation of atrial fibrillation: results from a worldwide survey in 34,943 atrial fibrillation ablation procedures. Circ Arrhythm Electrophysiol 2014;7:274–280. 18. Shoemaker MB, Muhammad R, Farrell M, et al. Relation of morbid obesity and female gender to risk of procedural complications in patients undergoing atrial fibrillation ablation. Am J Cardiol 2013;111:368–373. 19. Friberg J, Scharling H, Gadsbøll N, Jensen GB. Sex-specific increase in the prevalence of atrial fibrillation (The Copenhagen City Heart Study). Am J Cardiol 2003;92:1419–1423. 20. Go´mez-Doblas JJ, Mun˜iz J, Martin JJ, et al. Prevalencia de fibrilacio´n auricular en Espan˜a. Resultados del estudio OFRECE. Rev Esp Cardiol 2014;67:259–269. 21. Kirchhof P, Breithardt G, Camm AJ, et al. Improving outcomes in patients with atrial fibrillation: Rationale and design of the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial. Am Heart J 2013;166:442–448.
Address correspondence to: Josep M. Alegret, MD, PhD Grup de Recerca Cardiovascular Departament de Medicina i Cirurgia Universitat Rovira i Virgili Hospital Universitari de Sant Joan c/Dr. Josep Laporte, 1 Reus 43204 Spain E-mail: [email protected]
Gender Differences in Patients with Atrial Fibrillation Undergoing Electrical Cardioversion Josep M. Alegret, MD, PhD,1 Xavier Vin˜olas, MD, PhD,2 Antoni Martı´nez-Rubio, MD, PhD,3 Alonso Pedrote, MD,4 Xulio Beiras, MD, PhD,5 Jesu´s F. Garcı´a-Sacrista´n, MD,6 Francisco Crespo-Mancebo, MD,7 and Francisco Ruiz-Mateas, MD 8
Abstract
Background: Current recommendations on the rhythm control strategy for treatment of atrial fibrillation (AF) are more restrictive than a decade ago. Gender may play a role in decisions on the management of AF, including application of electrical cardioversion. Methods: We analyzed clinical characteristics by gender in patients participating in the observational survey about stable patients underlying cardioversion in Spain (CARDIOVERSE) study (n = 915), a survey of the practice of electrical cardioversion in 67 Spanish hospitals. We compared these data with those from a previous survey of electrical cardioversion in Spain (REVERSE study) performed 8 years previously. Results: Patients undergoing electrical cardioversion were mainly men (76%). This finding was observed in all age groups, independently of symptoms. Men were younger (62 – 10 years vs. 69 – 9 years; p < 0.001), more frequently asymptomatic and had a lower prevalence of hypertension and a lower stroke risk. Among asymptomatic patients, the predominance of men was especially evident in older age groups ( < 65 years, men 76%, women 24%; ‡ 65 years, men 92%, women 8% ( p < 0.001). Compared with the REVERSE study, we observed a decrease in the percentage of women among patients undergoing electrical cardioversion (37% REVERSE vs. 24% CARDIOVERSE; p < 0.001), mainly in older than 65 years. Conclusions: Our results support the hypothesis that gender is a determinant in decisions on the most appropriate strategy for managing AF. We observed a decrease in the percentage of women undergoing electrical cardioversion during the last decade, especially in older asymptomatic patients. Introduction
T
he atrial fibrillation follow-up investigation of rhythm management (AFFIRM) and rate versus electrical cardioversion for permanent atrial fibrillation study (RACE) trials1,2 demonstrated no differences in morbidity and mortality when comparing rate control strategies with rhythm control strategies in patients with atrial fibrillation (AF). The results of both trials have influenced guidelines3,4 and clinical practice, leading to stricter criteria for rhythm control strategies and less frequent use of electrical cardioversion.5,6 Gender differences have been observed in the management of ischemic heart disease, with more conservative management reported in women.7,8 Previous studies also revealed gender
differences in the clinical characteristics of patients with AF and in the management of AF. Thus, women with AF are older, more symptomatic, and seem to be at a higher risk of stroke.9–12 Data from the Euro Heart Survey on Atrial Fibrillation suggested less frequent use of rhythm control strategies in women.13 Patients treated with cardioversion represent persistent AF patients treated with rhythm control strategy. In the present study, we investigated the possible influence of gender in decisions on the treatment of patients with AF during the last decade. We analyzed gender-related clinical characteristics in the observational survey about stable patients underlying cardioversion in Spain (CARDIOVERSE) study, a Spanish survey of patients undergoing electrical cardioversion. We also compared the gender distribution in
1
Grup de Recerca Cardiovascular, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain. Hospital de la Sta. Creu i St. Pau, Barcelona, Spain. Hospital Universitari Parc Taulı´, Sabadell, Spain. 4 Hospital Universitario Virgen del Rocı´o, Sevilla, Spain. 5 Complejo Hospitalario Universitario de Vigo, Vigo, Spain. 6 Hospital General de Albacete, Albacete, Spain. 7 Hospital Lucus Augusti, Lugo, Spain. 8 Hospital Costa del Sol, Marbella, Spain. 2 3
466
UNDERUSE OF ELECTRICAL CARDIOVERSION IN WOMEN
the CARDIOVERSE study with that of the REVERSE study,14 a survey of electrical cardioversion in Spain performed 8 years previously. Methods
The CARDIOVERSE study was designed to monitor the clinical practice of elective electrical cardioversion in Spain
467
by prospectively recording all patients with persistent AF who underwent the procedure between February 1 and June 30, 2012, in 67 Spanish hospitals (Supplementary Appendix S1; Supplementary Data are available online at www .liebertpub.com/jwh). Nine hundred and fifteen consecutive patients were included. The inclusion criteria were age > 18 years, duration of AF > 7 days, and absence of precipitating conditions (e.g., hyperthyroidism, fever, cardiac surgery, and
Table 1. Characteristics of 915 Patient Participants in the CARDIOVERSE Study Segregated by Gender
Age, years BMI, kg/m2 BSA, m2 LA, mm Indexed LA, mm/m2 LVEF, quantitative LVEF, qualitative, n (%) Normal ( ‡ 50%) Slightly depressed (41%–49%) Moderately (31%–40%) Severely ( £ 30%) Hypertension, n (%) Diabetes mellitus, n (%) LV hypertrophy, n (%) Pulmonary disease, n (%) Valvulopathy, n (%) Congestive heart failure, n (%) NYHA, n (%) Class 1 Class 2 Class 3 Class 4 Previous electrical CV, n (%) CHADS2, n (%) Low risk (score = 0) Medium risk (score = 1) High risk (score ‡ 2) CHA2DS2VASc, n (%) Low risk (score = 0) Low-medium risk (score = 1) Medium-high risk (score ‡ 2) HAS-BLED, n (%) Low-medium risk (score < 3) High risk (score ‡ 3) Duration of AF, n (%) 8 days–1 month 1–3 months 3–12 months > 12 months Unknown Symptoms related to AF, n (%) (EHRA scale) 1. No symptoms 2. Mild (normal daily activity not affected) 3. Severe (normal daily activity affected) 4. Disabling (normal daily activity discontinued)
Men (n = 694)
Women (n = 221)
p
61.9 – 10.1 29.4 – 4.3 2.00 – 0.17 44.3 – 5.8 22.3 – 3.4 56.6 – 11.9
68.3 – 8.6 29.6 – 5.7 1.78 – 0.17 42.7 – 5.8 24.4 – 3.9 59 – 10.6
< 0.001 0.54 < 0.001 0.001 < 0.001 0.02
497 66 40 41 398 138 195 82 62 110
(77) (10) (6) (6) (57) (20) (30) (12) (30) (16)
174 14 12 6 149 37 45 7 44 47
(85) (7) (6) (3) (67) (17) (22) (3) (65) (21)
153 416 118 7 121
(22) (60) (17) (1) (17)
37 137 38 9 41
(17) (62) (17) (4) (18)
0.09
0.009 0.33 0.02 < 0.001 < 0.001 0.06 0.51
0.75
209 (30) 284 (41) 201 (29)
43 (19) 83 (38) 95 (43)
< 0.001
142 (20) 214 (31) 338 (49)
0 (0) 19 (9) 202 (91)
< 0.001
641 (92) 53 (8)
206 (93) 15 (7)
0.67
31 187 253 118 105
(5) (27) (37) (17) (19)
15 53 84 38 31
(7) (24) (38) (17) (14)
0.62
313 319 50 6
(46) (46) (7) (1)
57 130 26 6
(26) (59) (12) (3)
< 0.001
Values represent mean – standard deviation or n (%). AF, atrial fibrillation; BMI, body mass index; BSA, body surface area; CARDIOVERSE, observational survey about stable patients underlying cardioversion in Spain; CHADS2, hypertension, age ‡ 75 years, diabetes mellitus, stroke; CHA2DS2VASc, congestive heart failure, hypertension, age ‡ 75 years, diabetes mellitus, stroke, vascular disease, age 65–74 years, sex category; CV, cardioversion; EHRA, European Heart Rhythm Association; HAS-BLED, hypertension, abnormal renal, liver function, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly; LA, left atrium; LVEF, left ventricle ejection fraction; NYHA, New York Heart Association.
468
ALEGRET ET AL.
pericarditis). Patients were followed for 1 year (visits at 1, 3, 6, and 12 months after cardioversion) We analyzed the clinical characteristics of participants by gender and compared the results with those obtained in the REVERSE study, a survey on electrical cardioversion carried out in 96 Spanish hospitals by our group in between January 1 and June 30, 2004, with the same inclusion criteria.14,15 One thousand five hundred and fifteen patients were included. In that survey, the one-year follow-up was only applied to patients who did not have structural heart disease. Statistical analyses
Continuous variables are expressed as mean – standard deviation, and comparisons between groups were made using the t test for independent values. Categorical variables are expressed as percentages and were analyzed using the chisquared test. Differences were considered statistically significant if p < 0.05. The statistical analysis was performed using SPSS statistical software package (version 18). The study was approved by the institutional review boards (clinical ethics committee) of each participating hospital. Written informed consent was obtained from all the patients who participated in this study. Results
Patients were predominantly men (76%). Table 1 presents the clinical characteristics of patients segregated by gender. The predominance of men was observed in all age groups, although the percentage of women increased with age (Fig. 1). The percentage of patients who had previously undergone electrical cardioversion was similar for both men and women. Women were older and had a lower prevalence of left ventricular hypertrophy, and left ventricular dysfunction and a higher prevalence of hypertension and risk of stroke by hypertension, age ‡ 75 years, diabetes mellitus, stroke (CHADS2) and congestive heart failure, hypertension, age ‡ 75 years, diabetes mellitus, stroke, vascular disease, age 65– 74 years, sex category (CHA2DS2VASc) scores. Men were predominant in symptomatic (69%) as well asymptomatic patients (85%). The predominance of men in asymptomatic
FIG. 1. Distribution of men and women segregated depending on the age range.
FIG. 2. Comparison of the proportion of women between the survey about cardioversion in Spain (REVERSE) and observational survey about stable patients underlying cardioversion in Spain (CARDIOVERSE) studies depending on the age range. patients was especially evident in older patients ( < 65 years, men 76% vs. women 24%; ‡ 65 years, men 92% vs. women 8%; p < 0.001). With respect to the REVERSE study, we noted a decrease in the proportion of women undergoing cardioversion (CARDIOVERSE 24% vs. REVERSE 37%; p < 0.001) in all age groups. This decrease was more evident in patients > 65 years old (Fig. 2). Women participating in the REVERSE study had higher left atrial size, higher left ventricular ejection fraction and better functional class (Table 2).
Table 2. Differences in the Characteristics of Women Included in the REVERSE and CARDIOVERSE Studies REVERSE CARDIOVERSE n = 557 n = 221 Age, years Age ‡ 70 years BMI, kg/m2 BSA, m2 LA, mm Indexed LA, mm/m2 LVEF, quantitative Normal LVEF ( ‡ 50%), n (%) Hypertension, n (%) Diabetes mellitus, n (%) Pulmonary disease, n (%) NYHA ‡ II, n (%) Previous electrical CV, n (%) CHADS2 ‡ 2, n (%) Duration of AF > 12 months, n (%)
p
67.7 – 9.8 270 (49) 29.1 – 5.4 1.79 – 0.17 44.4 – 6.2 25 – 4.0 61.4 – 9.6 511 (92)
68.3 – 8.6 99 (45) 29.6 – 5.7 1.78 – 0.17 42.7 – 5.8 24.4 – 3.9 59 – 10.6 174 (85)
0.43 0.35 0.25 0.46 < 0.001 0.05 0.002 < 0.001
344 (62) 101 (18)
149 (67) 37 (17)
0.14 0.65
35 (6)
7 (3)
0.03
325 (58) 104 (19)
184 (83) 41 (18)
< 0.001 0.97
201 (36) 48 (9)
95 (43) 38 (17)
0.07 0.006
Values represent mean – standard deviation or n (%). REVERSE, survey about cardioversion in Spain.
UNDERUSE OF ELECTRICAL CARDIOVERSION IN WOMEN
We observed in both genders a similar rate of successful electrical cardioversion (men 92% vs. women 94%; p = 0.26), maintenance of sinus rhythm at one month (men 58% vs. women 57%; p = 0.91) and at one year (men 32% vs. women 29%; p = 0.48). Discussion
Fewer women than men underwent electrical cardioversion. This difference was observed in all the age groups and was independent of the presence of AF symptoms. The greatest difference was in asymptomatic patients in the oldest quartile. In the last decade, fewer women underwent electrical cardioversion, especially in the oldest age group. Our results suggest that electrical cardioversion is underused in women and that gender is taken into account when deciding on the AF strategy to be applied. Current guidelines recommend stricter criteria for the rhythm control strategy and suggest using electrical cardioversion less frequently. Patients undergoing electrical cardioversion today are more symptomatic and with a higher cardiovascular disease burden.6 We have observed similar findings in women, comparing their clinical characteristics at REVERSE and CARDIOVERSE studies. It is difficult to speculate about the reasons for variations in use of electrical cardioversion depending on gender. Differences could be due, in part, to a lower prevalence of symptomatic women in the population. However, epidemiological data on patients recently diagnosed with AF showed that women were more likely to have symptomatic AF than men.9 In addition, the percentage of men was higher in both symptomatic patients and in asymptomatic patients, and men predominated in all the age groups. The poorer prognosis of women treated with a rhythm control strategy described in the RACE study could have some influence on the decrease in the percentage of women undergoing electrical cardioversion in the last decade.16 Moreover, a higher risk of complications has been described in women undergoing AF ablation17,18 a technique also implicated in the rhythm control strategy. We cannot conclude that the lower use of electrical cardioversion in women was based solely on the cardiologist decision. In the usual discussion with the patient about the different treatment options, perhaps women are less predisposed to be treated with rhythm control strategy. Further studies are needed to explore the possible gender differences in the perceived risk of cardioversion and stroke. The main limitation of our study was that we analyzed a group of patients undergoing electrical cardioversion but not the management of patients diagnosed with AF in the population. Previous European epidemiological studies showed an increasing prevalence of AF with aging and higher AF prevalence and incidence in men than in women,9,18 although the total number of women with AF was higher due to the predominance of women in the oldest age groups. Recent data about the prevalence of AF in Spain show a similar overall prevalence in men and women,20 although this differed depending on the age group analyzed, with the percentage of women increasing steeply after 60 years. Taking into account the percentage of women in the different ranges of age analyzed in that study, our data clearly suggest a lower use of electrical cardioversion in all the range of age in women. We have observed in women undergoing electrical
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cardioversion an increased risk of stroke risk evidenced by higher CHADS2/CHA2DS2VASc scores. This was due to a higher prevalence of hypertension and heart failure, but mainly to their older age, as seen in the increased prevalence of women when the age range increased. In treating AF, one of the ways to prevent stroke could be to prevent AF. Women are at higher risk of stroke, but perhaps are not treated as aggressively to achieve and maintain sinus rhythm, which could help to decrease stroke risk. The ongoing EAST study may clarify whether a strict rhythm control strategy can reduce the incidence of stroke.21 In conclusion, our results support the hypothesis that gender is a determinant in decisions on the most appropriate strategy for managing AF, independently of other clinical factors. We observed a decrease in the percentage of women undergoing electrical cardioversion during the last decade, especially in older asymptomatic patients. Acknowledgments
This study was funded by Bayer Health Care Spain. Author Disclosure Statement
No competing financial interests exist. References
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Address correspondence to: Josep M. Alegret, MD, PhD Grup de Recerca Cardiovascular Departament de Medicina i Cirurgia Universitat Rovira i Virgili Hospital Universitari de Sant Joan c/Dr. Josep Laporte, 1 Reus 43204 Spain E-mail: [email protected]
