Clinical Interventions in Aging Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Improvement in Atrial Fibrillation-Related Symptoms After Cardioversion: Role of NYHA Functional Class and Maintenance of Sinus Rhythm Clinical Interventions in Aging downloaded from https://www.dovepress.com/ on 01-Apr-2023 Maria Ferre-Vallverdu 1–3 Background: The European Heart Rhythm Association (EHRA) score is a proven and Carmen Ligero 1–3 validated tool for assessing the symptoms of atrial fibrillation (AF). Little is known about the Rafael Vidal-Perez 4 variables related to this score and how it changes after cardioversion. Antoni Martinez-Rubio 5 Methods: We analyzed 744 patients undergoing elective cardioversion in whom AF-related For personal use only. symptoms were assessed at baseline and after 6 months of follow-up using the EHRA score. Xavier Vinolas 6 We assessed the association between the EHRA score and other clinical and echocardio­ Josep M Alegret 1–3 graphic variables at baseline and after 6 months of follow-up. 1 Department of Cardiology, Hospital Results: At 6 months of follow-up, we observed a reduction in the EHRA score in 50% and Universitari de Sant Joan; 2Institut d'Investigació Sanitària Pere Virgili worsening in 2.8% of patients who remained in sinus rhythm (SR) compared with 34.6% and (IISPV); 3Department of Medicine and 11.3%, respectively, of patients with AF episodes (p<0.0001). Patients who maintained SR at Surgery of the University Rovira i Virgili; 6 months were less symptomatic than those with AF (EHRA score 1.13 ± 0.35 vs 1.42 ± Reus, Spain; 4Department of Cardiology, Complejo Hospitalario Universitario de 0.59; p<0.0001). The independent predictors for reduction in the EHRA score after cardio­ A Coruña, A Coruña, Spain; 5Department version were NYHA ≥II at baseline and maintenance of SR (p<0.0001). of Cardiology, Hospital Parc Taulí, Conclusion: The greatest improvement in AF-related symptoms was in patients who Sabadell, Spain; 6Department of Cardiology, Hospital de la Sta, Creu i St remained in SR at 6 months after cardioversion and in patients with worse NYHA functional Pau, Barcelona, Spain class at baseline. Keywords: atrial fibrillation, EHRA score, cardioversion, NYHA functional class, sinus rhythm, symptoms improvement Introduction It has been widely reported that patients with atrial fibrillation (AF) have signifi­ cantly poorer quality of life (QoL) than healthy controls.1 A substantial proportion of patients with AF have associated symptoms,2,3 and the severity of these symp­ toms has been closely correlated with impaired QoL.4 The European Heart Rhythm Association (EHRA) score has been shown to be a useful tool for assessment of AF–related symptoms and has been validated for describing symptom severity.5,6 It is simple to use and is recommended by the European Society of Cardiology guidelines for management of AF.7 The EHRA score is considered one of the strongest predictors of QoL, regardless of the type of Correspondence: Josep M Alegret Department of Cardiology, Hospital AF, and is commonly used to assess improvement in symptoms after treatment Universitari de Sant Joan. Institut of AF.8 d'Investigació Sanitària Pere Virgili (IISPV). Department of Medicine and Surgery of Previous trials comparing rhythm and rate control strategies have reported neutral the University Rovira i Virgili; Reus, Spain. effects on stroke and mortality.9–11 However, very recently, the EAST-AFNET 4 trial has C/Dr Josep Laporte, 4, Reus, 43204, Spain Email josepmaria.alegret@urv.cat shown that early rhythm–control therapy was associated with a lower risk of Clinical Interventions in Aging 2021:16 739–745 739 © 2021 Ferre-Vallverdu et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/ terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Ferre-Vallverdu et al Dovepress cardiovascular outcomes.12 While both treatment strategies or class IV (disabling symptoms: normal daily activity have been associated with improvement in QoL,13–15 it is discontinued). The EHRA score was recorded before car­ still unclear which is superior.1,16 Cardioversion is recom­ dioversion and after 6 months of follow-up. The NYHA mended as part of rhythm control therapy in symptomatic symptom classification was also recorded at the beginning patients with persistent or long-standing persistent AF.7 of the study. However, changes symptoms related to AF after cardiover­ Maintenance of sinus rhythm (SR) during follow-up sion have received little attention in the literature. was defined as the absence of recurrence of AF at visit In this study, we assessed the main predictors of AF- 1, visit 3, and visit 6. related symptoms based on the EHRA score at baseline and 6 months after cardioversion. Statistical Analysis Normally distributed continuous data are presented as Methods mean ± SD. Categorical variables are presented as fre­ Study Population quencies and percentages. The CARDIOVERSE study was designed to monitor the Differences in continuous variables between categories clinical practice of elective electrical cardioversion in of patients were studied using an unpaired t-test or Spain by prospectively recording all patients with per­ ANOVA, where applicable. A paired t-test was used to sistent AF who underwent the procedure between analyze the differences in the mean EHRA score between February 1 and June 30, 2012 in 67 Spanish the initial score and at 6 months of follow-up. hospitals.17 The study population comprised 915 Differences in proportions were analyzed using the chi- patients. The inclusion criteria were age > 18 years, square test. Correlations between the NYHA classification duration of AF > 7 days, and absence of precipitating and the EHRA score were assessed using Spearman cor­ conditions (eg, hyperthyroidism, fever, cardiac surgery, relation coefficient. Univariable and multivariable regres­ and pericarditis). Pre-procedural antiarrhythmic drugs sion analysis were performed to assess predictors of being could be prescribed at the discretion of the physician. symptomatic (EHRA score ≥ II) at baseline (logistic Those patients treated with antiarrhythmic drugs who regression) and to characterize predictors of a change in reverted to SR previous to electrical cardioversion EHRA score 6 months after cardioversion (linear were considered who had a pharmacological cardiover­ regression). sion. Patients were followed for 1 year (visits at 1, 3, 6, All statistical tests were performed using IBM SPSS and 12 months after cardioversion). Statistics for Windows, Version 20.0. A 2-tailed p value < AF-related symptoms assessment according to the 0.05 was considered statistically significant. EHRA classification was planned in the design of the CARDIOVERSE study. In this report, we selected retro­ spectively 744 patients with a complete record of the Results EHRA score before cardioversion and after 6 months of Patient Characteristics follow-up. Patients who underwent pulmonary vein abla­ Cardioversion was successful in 624 of the 744 patients tion during follow–up were excluded. included (83.9%: electrical cardioversion, n=560 [75.3%]; The study was conducted according to the principles of pharmacological cardioversion, n=64, [8.6%]). the Declaration of Helsinki and was approved by the local Cardioversion failed in the remaining 120 patients (16.1%). ethic committees (Hospital Universitari Sant Joan de Reus The mean age was 63 years, and 77% were male. 11-12-22/12obs3). Written informed consent was obtained The most common comorbidity was hypertension from all the patients who participated in this study. (59.9%), and 29.8% of patients had structural heart disease. Baseline clinical characteristics according to Evaluation of Symptoms the EHRA score are presented in Table 1. The clinical The physician categorized AF-related symptoms according characteristics of the patients excluded because their to the EHRA classification as class I (no symptoms), class EHRA score was not available were similar to those of II (mild symptoms: normal daily activity not affected), the patients included in this analysis (Supplementary class III (severe symptoms: normal daily activity affected), Table 1). 740 http://doi.org/10.2147/CIA.S305619 Clinical Interventions in Aging 2021:16 DovePress Powered by TCPDF (www.tcpdf.org) Dovepress Ferre-Vallverdu et al Table 1 Baseline Characteristics According to EHRA Score N=744 EHRA I (311) EHRA II (363) EHRA III/IV (70) p Age 63 ± 10 62 ± 9 64 ± 10 65 ± 11 0.004 Female 169 (22.7%) 45 (14.5%) 100 (27.5%) 24 (34.3%) <0.0001 DM 143 (19.2%) 48 (15.4%) 77 (21.2%) 18 (25.7%) 0.06 Hypertension 446 (59.9%) 169 (54.3%) 237 (65.3%) 40 (57.1%) 0.013 COPD 77 (10.3%) 25 (8%) 44 (12.1%) 8 (11.4%) 0.212 Structural heart disease 222 (29.8%) 61 (19.6%) 125 (34.4%) 36 (51.4%) <0.0001 Prior stroke 41 (5.5%) 14 (4.5%) 25 (6.9%) 2 (2.9%) 0.237 Duration of AF Persistent AF 509 (68.4%) 185 (59.5%) 271 (74.6%) 53 (75.7%) <0.0001 Long-standing persistent AF (>1 year) 132 (17.7%) 69 (22.2%) 55 (15.2%) 8 (11.4%) Unknown 103 (13.8%) 57 (18.3%) 37 (10.2%) 9 (12.9%) CHA2DS2VASC <2 304 (40.9%) 160 (51.4%) 125 (34.4%) 19 (27.1%) <0.0001 ≥2 440 (59.1%) 151 (48.6%) 238 (65.6%) 51 (72.9%) HASBLED <2 555 (74.6%) 243 (78.1%) 265 (73%) 47 (66.1%) 0.101 ≥2 189 (25.4%) 68 (21.9%) 98 (27%) 23 (32.9%) NYHA classification I 648 (87.1%) 307 (98.7%) 297 (81.8%) 44 (62.9%) <0.0001 II, III, IV 96 (12.9%) 4 (1.3%) 66 (18.2%) 26 (37.1%) LVEF (%) 57 ± 11 59 ± 9 56 ± 12 49 ± 16 <0.0001 LA diameter 44 ± 6 44 ± 6 43 ± 6 46 ± 6 0.032 Antiarrhythmic therapy Flecainide/propafenone 77 (10.3%) 41 (13.2%) 32 (8.8%) 4 (5.7%) 0.593 Amiodarone 216 (29%) 83 (26.7%) 116 (32%) 17 (24.3%) Other 19 (2.6%) 9 (2.9%) 9 (2.5%) 1 (1.4%) Other treatment Betablockers 465 (62.5%) 181 (58.2%) 234 (64.5%) 50 (71.4%) 0.066 Calcium blockers 133 (17.9%) 56 (18%) 67 (18.5%) 10 (14.3%) 0.704 Digoxin 76 (10.2%) 23 (7.4%) 42 (11.6%) 11 (15.7%) 0.057 ACEi/ARB 390 (52.4%) 150 (48.2%) 199 (54.8%) 41 (58.6%) 0.129 Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; AF, atrial fibrillation; ARB, angiotensin receptor blocker; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; LA; left atrium; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association. Clinical Interventions in Aging 2021:16 http://doi.org/10.2147/CIA.S305619 741 DovePress Powered by TCPDF (www.tcpdf.org) Ferre-Vallverdu et al Dovepress Symptom Burden at Baseline At enrolment, 311 patients (41.8%) were classified as having no AF–related symptoms (EHRA I). The remaining patients were classified as having mild symptoms (EHRA II, 48.8%), severe symptoms (EHRA III, 8.2%), and dis­ abling symptoms (EHRA IV, 1.2%). Compared with asymptomatic patients (EHRA I), symptomatic patients (EHRA score ≥ II) were older (64 ± 10 vs 62 ± 9 years; p = 0.001) and more likely to be female (28.6% vs 14.5%; p < 0.0001). They also had a greater prevalence of struc­ tural heart disease (37.2% vs 19.6%; p < 0.0001), diabetes mellitus (21.9% vs 15.4%; p = 0.026), and hypertension (64% vs 54.3%; p = 0.008), as well as a higher NYHA Figure 1 Mean EHRA score at baseline and after 6 months of follow-up in the study population, in patients who maintained sinus rhythm, and in patients who classification (21.2% in class II–IV vs 1.3%; p < 0.0001) experienced recurrence of AF. and lower left ventricular ejection fraction (LVEF) (55 ± 13 vs 59 ± 9; p < 0.0001). The independent predictors for being symptomatic (EHRA score II-IV) at baseline were patients with SR compared with 54.1% of those whose AF female gender (OR = 2.22; 95% CI, 1.44–3.42; p < relapsed. The EHRA score increased in 2.8% of patients in 0.0001), and the strongest predictor was being in NYHA SR compared with 11.3% of those whose AF relapsed (p < class II–IV (OR = 12.5; 95% CI, 4.4–35.4; p < 0.0001). 0.0001). Figure 2. (Supplementary Table 2) In the univariable analysis, the factors associated with We observed a significant correlation when comparing a change in EHRA score at 6 months were structural heart baseline EHRA score with NYHA score (R = 0.334, p < disease, baseline NYHA classification ≥ 2, LVEF, and 0.0001). The correlation was more pronounced in patients maintenance of SR. In the multivariable linear analysis to with LVEF ≤ 40% (R = 0.506, p < 0.0001) than in patients predict change in EHRA score at 6 months after cardio­ with LVEF > 40% (R = 0.264, p < 0.0001). version, the only statistically significant variables were NYHA classification ≥ 2 (β = –0.178; p < 0.0001) and maintenance of SR (β = –0.162; p < 0.0001). (Table 2) Predictors of Improvement in AF-Related Symptoms at 6 Months During follow-up, 282 patients (37.9%) maintained SR. In Discussion the cohort that maintained SR, mean EHRA score In the present study, we identified variables related to the improved during follow-up (1.13 ± 0.35) with respect to EHRA score at baseline and to improvement in the EHRA baseline (1.67 ± 0.63), (p < 0.0001). However, in patients score after cardioversion. We highlight that maintenance who did not maintain SR, symptoms also improved during of SR at 6 months was related to an improved EHRA follow-up (1.42 ± 0.59 at 6 months vs 1.7 ± 0.7 at base­ score. We also highlight the influence of the NYHA as line; p < 0.0001). Otherwise, patients who maintained SR a predictor of improvement in the EHRA score, a higher were less symptomatic at 6 months than patients whose NYHA functional class at baseline was related to a more AF relapsed (1.13 ± 0.35 vs 1.42 ± 0.59; p < 0.0001), pronounced decrease in EHRA score at 6 months. despite having similar symptoms at baseline (1.67 ± 0.63 AF-related symptoms diminished during follow-up in vs 1.7 ± 0.7; p = 0.57). Figure 1. the group as a whole, probably indicating greater tolerance Six months after cardioversion, the EHRA score and better control of heart rate. However, we observed few decreased in 301 patients (40.4%), remained unchanged symptoms in those who remained in SR, thus indicating in 383 patients (51.5%), and worsened in 60 (8.1%). When that maintenance of SR was the strongest independent patients were stratified according to maintenance of SR, predictor of an improvement in AF–related symptoms. the EHRA score fell in 50% of those who maintained SR The role of maintaining SR in improvement in symptoms compared with 34.6% of those who did not maintain SR, remains controversial.18–20 A recent subanalysis of the while no change in EHRA score was observed in 47.2% of CABANA trial showed that higher rates of maintenance 742 http://doi.org/10.2147/CIA.S305619 Clinical Interventions in Aging 2021:16 DovePress Powered by TCPDF (www.tcpdf.org) Dovepress Ferre-Vallverdu et al Figure 2 Change in EHRA at 6 months after cardioversion in patients who maintained sinus rhythm and in patients with recurrence of AF. of SR achieved using AF ablation were related to control strategy with cardioversion followed by pulmonary a significant improvement in QoL.21 On the other hand, vein ablation. a report from the ORBIT-AF registry which compared The many variables that may influence the EHRA matched cardioverted and non-cardioverted patients, score have been reported in different registries and include showed an improvement in AF-related symptoms and female gender, coronary artery disease, heart failure, AF quality of life with both strategies.22 However, in that non- type, chronic obstructive pulmonary disease, sleep apnea, randomized study, which included all types of AF, main­ limited physical activity, and poor sleep quality.2–4,23 The tenance of SR during follow-up was not considered in the relationship between heart failure and AF has been exten­ analysis. Given our results and these observations, indivi­ sively investigated in the literature, which shows that both dualized decisions should be based on AF–related symp­ diseases are linked by similar risk factors, share a common toms, and the probable benefit of maintaining SR should pathophysiology,24,25 and frequently present with similar symptoms. The NYHA scale has been widely used to be taken into consideration. Therefore, in many cases, it assess symptoms of heart failure, although, to the best of may be necessary to consider complementing the rhythm our knowledge, the relationship between the NYHA scale classification and the EHRA score had not been previously Table 2 Univariable and Multivariable Linear Regression Analysis evaluated. In our study, we observed a direct correlation for Prediction of Change in EHRA Score between baseline NYHA functional class and the EHRA scale, suggesting that the greater the deterioration of the Univariable Multivariable functional class, the worse the tolerance to AF. This cor­ β p value β p value relation was even stronger in patients with reduced LVEF, Age (years) –0.012 0.74 – – probably owing to the well-documented heterogeneity in Female sex –0.07 0.055 –0.61 0,1 heart failure with preserved LVEF. At the same time, after Structural heart disease –0.112 0.002 –0.23 0.584 cardioversion, we observed a greater symptomatic benefit NYHA classification ≥2 –0.214 <0.0001 –0.178 <0.0001 related to AF in patients with a worse baseline NYHA LVEF –0.146 <0.0001 –0.065 0,128 Maintenance of SR –0.17 <0.0001 –0.162 <0.0001 functional class; those with a worse functional class at Antiarrhythmic treatment –0.096 0.09 – – baseline were those who had a greater opportunity to Abbreviations: LVEF, left ventricular ejection fraction; NYHA, New York Heart improve during follow–up. On the other hand, there is Association; SR, sinus rhythm. likely to be an overlap in the patient’s interpretation of Clinical Interventions in Aging 2021:16 http://doi.org/10.2147/CIA.S305619 743 DovePress Powered by TCPDF (www.tcpdf.org) Ferre-Vallverdu et al Dovepress heart failure and symptoms of AF, as dyspnea on exertion collection and analysis, decision to publish, or preparation is one of the main symptoms of AF.4 of the manuscript.”“All authors made substantial contribu­ We found that patients who were symptomatic at base­ tions to conception and design, acquisition of data, or line (EHRA II-IV) were older and more likely to be analysis and interpretation of data; took part in drafting female. Other reports point to older age as a significant the article or revising it critically for important intellectual predictor of asymptomatic AF.2 However, we previously content; agreed to submit to the current journal; gave final reported the predominance of older men undergoing car­ approval of the version to be published; and agree to be dioversion. Our results suggest a trend toward selecting accountable for all aspects of the work.” older and more symptomatic patients for cardioversion. Although current recommendations state that rhythm control therapy is indicated to improve symptoms,7 we Disclosure The authors report no conflicts of interest in this work. were surprised by the high proportion of asymptomatic patients (41.8%) who underwent cardioversion. Other stu­ dies have reported a high proportion of asymptomatic References patients undergoing AF ablation.26 This may reflect the 1. Thrall G, Lane D, Carroll D, Lip GYH. 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