Atrial fibrillation (AF), with a prevalence rate of 0.95% in the adult population, is the most common arrhythmia of clinical significance.1–3 AF adversely impacts the quality of life and increases mortality.3–6 Radiofrequency catheter ablation offers the benefits of maintaining sinus rhythm while without the adverse effects of antiarrhythmia drugs (AADs). However, the success rate is still unsatisfactory.7
Studies using the health-related quality of life instruments have suggested that patients diagnosed with AF experience more psychological distress, which in the form of anxiety and depression is related to increased mortality, morbidity, and consumption of healthcare, than do healthy controls.8–10 The study performed by Lange and Herrmann-Lingen11 indicates that depression is a major risk factor for recurrence of AF after electrical cardioversion. The effect of circumferential pulmonary vein ablation (CPVA) on anxiety and depression in patients with persistent AF and the effect of anxiety and depression on the recurrence of persistent AF after CPVA are not clear. This study aims to investigate the influence of CPVA on anxiety and depression of persistent AF and whether the anxiety or depression symptoms can increase the recurrence risk of persistent AF after CPVA.
Between October 2006 and October 2009, 164 patients with a diagnosis of persistent AF consecutively admitted to the Department of Cardiology, Renmin Hospital of Wuhan University. Persistent AF was defined as AF episodes lasting more than seven days or cannot self-terminated which need cardioversion. Forty-three patients who underwent CPVA (CPVA group) and 121 accepted AADs only (medicine group) were enrolled in the present study. All patients were educated and none of them had troubles on communication. All the procedures were approved by the Reviewer Institutional Committee on Human Research of the Renmim Hospital that conforms to the Declaration of Wuhan University. Patients were excluded if they had a history of myocardial infarction in the last 12 months, cardiac surgery or congenital heart disease, pericardial disease, a history of cancer, tuberculosis, hyperthyroidism or hypothyroidism, rheumatism, decompensate liver cirrhosis or serum creatinine level >2 mg/dl. All patients underwent a clinical evaluation, which included a complete medical history, physical examination, electrocardiography, chest radiography, echocardio-graphy, and the laboratory tests. Anxiety symptoms (Zung Self-Rating Anxiety Scale (SAS)) and depression symptoms (Zung Self-Rating Depression Scale (SDS)) were assessed in the hospital before and 12 months after treatment in all patients.
The decision to undergo catheter ablation or medical treatment was left to the patient's own preferences or to the judgment of the electrophysiologist involved in each case. The study was approved by the hospital's ethics committee, and all patients gave their written informed consent.
Treatment of AF
The ablation technique details have been published previously.12 Briefly, three-dimensional left atrial maps and pulmonary vein profiles were reconstructed through a transseptal route using a nonfluoroscopic electrogeometric mapping system (CARTO, Biosense-Webster, Inc., USA). After characterizing pulmonary vein ostia, radiofrequency energy was delivered by the distal electrode of the navigation catheter to create circular lines of conduction block around each vein ostium. Both antiarrhythmics and anticoagulation were discontinued in the first three months after CPVA in the absence of recurrences. AADs were performed to control sinus rhythm.
SAS and SDS
The SAS was designed by Zung13 to quantify the level of anxiety for patients experiencing anxiety related symptoms. The self-administered test has 20 questions. Each question is scored on a scale of 1–4 based on these replies: none or a little of the time, some of the time, good part of the time, most of the time. There are fifteen questions worded toward increasing anxiety levels and five questions worded toward decreasing anxiety levels. The normal score equals the total score multiplied by 1.25. The score ranges from 20 to 80 and the normal range is 20–44, mild to moderate anxiety levels 45–59, marked to severe anxiety levels 60–74, and an extreme anxiety level is 75–80.13 The reliability and the validity of SAS have been examined in several studies.14–16
The SDS is a short self-administered survey to quantify the depression status of a patient designed by Zung. There are 20 items on the scale that rate the four common characteristics of depression: the pervasive effect, the physiological equivalents, other disturbances, and psychomotor activities. There are ten positively worded and ten negatively worded questions. Each question is scored on a scale of 1–4 based on these replies: none or a little of the time, some of the time, good part of the time, or most of the time. The normal score equals the total score multiplied by 1.25. The score on the test ranges from 20 to 80. The normal range is 20–49, mildly depressed 50–59, moderately depressed 60–69, and severely depressed 70 and above.17 The reliability and validity of SDS have been evaluated in several studies.18–20
All patients were discharged on oral anticoagulation with a target international normalized ratio between 2 and 3. Warfarin was continued for a minimum of 3 months after the ablation procedure and maintained afterwards according to the prevalent rhythm and the CHADS2 score of the patients. AADs were stopped after a blanking period of 3 months for patients accepted CPVA. For patients performed AADs only, AADs were maintained through the study. All enrolled patients were followed up for 12 months. Patients were asked to return to the outpatient clinic or to their referring physician for electrocardiographic documentation. The 12-lead and 24-hour ambulatory ECG was measured after 3, 6, 9 and 12 months or as soon as they felt recurrent palpitations, whichever event occurred earlier. Ambulatory electrocardiographic recorders were used to correlate symptoms with arrhythmia recurrence. The AF recurrence was defined as the first documented AF recurrence >30 seconds. During follow-up, no patient withdraw in CPVA group and 103 patients in medicine group finished study. According to the results of follow-up, patients in CPVA group were divided into recurrent group and non-recurrent group.
Continuous variables were reported as mean ± standard deviation (SD). Discrete variables were reported as n (%). The χ2 and t statistic methods were used to compare the baseline characteristics, SAS and SDS of the CPVA and medicine groups, recurrent and non-recurrent groups at baseline, SAS and SDS of CPVA group, medicine group, recurrent and non-recurrent groups at baseline and 12 months. Univariate and multivariate Logistic regression methods were used to determinate the risk factors of AF recurrence after CPVA. All statistical tests were evaluated with the use of two-tailed 95% confidence levels, and tests with P <0.05 were considered significant. Data analyses were performed with the use of SPSS for Windows, release 15, 2006 (SPSS Inc., Chicago, III, USA).
General characteristics of patients
Clinical characteristics of patients are listed in Table 1. There was no significant difference between the two groups. Over 12 months follow-up, 17 patients had recurrent AF and 26 patients maintained sinus rhythm. The general characteristics of patients in the recurrent and non-recurrent groups are summarized in Table 2. The results showed that there were no significant differences in age, gender distribution, left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), 24-hour average heart rate, history of AF, hypertension, coronary heart disease, diabetes mellitus, and aortic regurgitation between the recurrent and non-recurrent groups. However, patients in the recurrent group suffered larger left atrial diameter (LAD) ((37.46±5.27) mm vs. (34.24±3.23) mm, P=0.02) and longer AF history ((3.56±0.51) years vs. (3.14±0.40) years, P <0.01) than the non-recurrent group.
Effect of CPVA on anxiety and depression
In the CPVA group, the normal scores of SAS (40.33±7.90 vs. 49.76±9.52, P <0.01) and SDS (42.33±8.73 vs. 48.17±8.77, P <0.01) declined significantly after CPVA (Table 3). While in medicine group, there were no differences on SAS or SDS between enrollment and 12 months later (Table 3).
Risk factors of 12 month AF recurrence after CPVA
The results of this study indicated that the normal scores on the SAS and SDS in the recurrent group were higher than in the non-recurrent group before follow-up (Table 4).
The independent risk factors of AF recurrence after CPVA were identified using a multivariate Logistic regression model through a stepwise procedure while controlling the effects of other variables. The LAD, normal score of SAS and normal score of SDS were entered into the multivariate regression analysis. Finally, LAD, AF history, normal score of SAS and normal score of SDS were determinate to be the independent risk factors of AF recurrence for persistent AF after CPVA (Table 5).
AF is the most common arrhythmia seen in clinical practice, accounting for approximately one-third of hospitalizations for cardiac rhythm disturbances. AF is associated with an increased long-term risk of stroke, heart failure and all-cause mortality.21 The mortality rate of patients with AF is about double that of patients with normal sinus rhythm and linked to the severity of underlying heart disease.22,23 CPVA, as an alternate method for AF therapy, affords a promising approach to control AF. However, the success rates free of AADs and the overall success rates are still unsatisfactory.7 Currently, the mechanism of AF recurrence after CPVA is not elucidated. Although relapse of PV conduction is the major cause of AF recurrence,24 it cannot fully explain why patients without re-connecting of PV-LA suffered AF recurrence after CPVA. Furthermore, other factors may affect the onset or sustain AF which may include anxiety or depression. Previous studies have shown that both anxiety and depression are widespread among cardiac patients.25–27 And the independence of anxiety and depression as predictors of cardiovascular disease outcome is supported by multiple studies.28–30 In the Framingham Offspring study, Eaker et al31,32 explored the association between psychological variables and supraventricular arrhythmias and identified anger and hostility, as well as anxiety, as significant risk factors in men for the development of AF in later life. Another study performed by Helmut indicated that depression is a major risk factor for recurrence of AF after electrical cardioversion.11 While the relationships between anxiety, depression and AF recurrence after CPVA is unclear.
A noteworthy finding from our study is that higher normal scores of SAS and SDS increase the 12-month recurrence risk of AF for paroxysmal AF patients after CPVA. Furthermore, we found the state of anxiety and symptoms of depression were significantly alleviated in patients in the CPVA group after follow-up. These results imply that anxiety and depression have a close relationship with AF recurrence. It is known that AF is initiated when an ectopic excitation encounters a fibrillation-prone substrate. Typical triggers for AF are abnormal activity of the autonomic nervous system, stretch, or rapidly firing ectopic foci located in the pulmonary veins. Studies have suggested that inflammation leads to atrial myocarditis resulting in initiation and maintenance of AF. The mechanism of psychosocial variables that increase the incidence and recurrence of AF may result from heightened adrenergic tone as evidenced by decreased HRV33 and a pro-inflammatory state such as C-reactive protein and inflammatory cytokines activated.34 The symptoms of anxiety and depression may reduce parasympathetic and increase sympathetic nervous system activity which can lower the threshold for AF.
There are several limitations in the present study. First, this study was performed in a single-center and has a relatively small sample size. The results need to be confirmed in a larger population and with multiple center trials. Furthermore, the decision to undergo catheter ablation or medical treatment was left to both the patient's own preferences or to the judgment of the electrophysiologist involved in each case, which may partly depend on the patient's economic statue, and are not random. Finally, we cannot exclude the fact that depression and anxiety that affect AF recurrence may be mediated by other factors, such as alcohol abuse, sleep disturbance, etc, which are more prevalent in those patients.
In conclusion, anxiety and depression increase the recurrence risk of patients with persistent AF after CPAV. CPVA can ameliorate the anxiety and depression statue.
1. Kasliwal RR, Mukesh S, Manohar G, Aggarwal N, Bhatia A. Pharmacotherapy of atrial fibrillation. Asian Cardiovasc Thorac Ann 2003; 11: 364-374.
2. Murgatroyd FD, Camm AJ. Atrial arrhythmias. Lancet 1993; 341: 1317-1322.
3. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285: 2370-2375.
4. Hohnloser SH, Kuck KH. Randomized trial of rhythm or rate control in atrial fibrillation: the Pharmacological Intervention in Atrial Fibrillation trial (PIAF). Eur Heart J 2001; 22: 801-802.
5. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, 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.
6. Narasimhan C, Blanck Z, Akhtar M. Atrioventricular nodal modification and atrioventricular junctional ablation for control of ventricular rate in atrial fibrillation. J Cardiovasc Electrophysiol 1998; 9 (8 Suppl): S146-S150.
7. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythmn Electrophysiol 2010; 3: 32-38.
8. McCabe PJ. Psychological distress in patients diagnosed with atrial fibrillation: the state of the science. J Cardiovasc Nurs 2010; 25: 40-51.
9. Nicholson A, Kuper H, Hemingway H. Depression as an etiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146538 participants in 54 observational studies. Eur Heart J 2006; 27: 2763-2774.
10. Rutledge T, Reis VA, Linke SE, Greenberg BH, Mills PJ. Depression in heart failure: a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes. J Am Coll Cardiol 2006; 48: 1527-1537.
11. Lange HW, Herrmann-Lingen C. Depressive symptoms predict recurrence
of atrial fibrillation after cardioversion. J Psychosom Res 2007; 63: 509-513.
12. Pappone C, Rosanio S, Oreto G, Tocchi M, Gugliotta F, Vicedomini G, et al. Circumferential radiofrequency ablation of pulmonary vein ostia: a new anatomic approach for curing atrial fibrillation. Circulation 2000; 102: 2619-2628.
13. Zung WW. A rating instrument for anxiety disorders. Psychosomatics 1971; 12: 371-379.
14. Jegede RO. Psychometric attributes of the self-rating anxiety scale. Psychol Rep 1977; 40: 303-306.
15. Olatunji BO, Deacon BJ, Abramowitz JS, Tolin DF. Dimensionality of somatic complaints: factor structure and psychometric properties of the self-rating anxiety scale. J Anxiety Disord 2006; 20: 543-561.
16. Michelson L, Mavissakalian M. Temporal stability of self-report measures in agoraphobia research. Behav Res Ther 1983; 21: 695-698.
17. Zung WW. A self-rating depression scale. Arch Gen Psychiatry 1965; 12: 63-70.
18. Zung WW. A cross-cultural survey of depressive symptomatology in normal adults. J Cross-Cult Psychol 1972; 3: 177-183.
19. Fountoulakis KN, Lacovides A, Samolis S, Kleanthous S, Kaprinis SG, St Kaprinis G, et al. Reliability, validity and psychometric properties of the Greek translation of the Zung Depression Rating Scale. BMC Psychiatry 2001; 1: 6.
20. Barefoot JC, Brummett BH, Helms MJ, Mark DB, Siegler IC, Williams RB. Depressive symptoms and survival of patients with coronary artery disease. Psychosom Med 2000; 62: 790-795.
21. Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. Am J Med 2002; 113: 359-364.
22. Flegel KM, Shipley MJ, Rose G. Risk of stroke in non-rheumatic atrial fibrillation. Lancet 1987; 1: 526-529.
23. Kannel WB, Abbott RD, Savage DD, McNamara PM. Coronary heart disease and atrial fibrillation: the Framingham Study. Am Heart J 1983; 106: 389-396.
24. Chen H, Yang B, Ju W, Zhang F, Hou X, Chen C, et al. Long-term clinical implication of the occurrence of dissociated pulmonary vein activities after circumferential left atrial ablation in patients with paroxysmal atrial fibrillation. Circ J 2010; 75: 73-79.
25. Roy-Byrne PP, Davidson KW, Kessler RC, Asmundson GJ, Goodwin RD, Kubzansky L, et al. Anxiety disorders and comorbid medical illness. Gen Hosp Psychiatry 2008; 30: 208-225.
26. Fan AZ, Strine TW, Jiles R, Mokdad AH. Depression and anxiety associated with cardiovascular disease among persons aged 45 years and older in 38 states of the United States. Prev Med 2008; 46: 445-450.
27. Herbst S, Pietrzak RH, Wagner J, White WB, Petry NM. Lifetime major depression is associated with coronary heart disease in older adults: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychosom Med 2007; 69: 729-734.
28. Shen BJ, Avivi YE, Todaro JF, Spiro A 3rd, Laurenceau JP, Ward KD, et al. Anxiety characteristics independently and prospectively predict myocardial infarction in men: the unique contribution of anxiety among psychological factors. J Am Coll Cardiol 2008; 51: 113-119.
29. Shibeshi WA, Young-Xu Y, Blatt CM. Anxiety worsens prognosis in patients with coronary artery disease. J Am Coll Cardiol 2007; 49: 2021-2027.
30. Albert CM, Chae CU, Rexrode KM, Manson JE, Kawachi I. Phobic anxiety and risk of coronary heart disease and sudden cardiac death among women. Circulation 2005; 111: 480-487.
31. Eaker ED, Sullivan LM, Kelly-Hayes M, D'Agostino RB, Benjamin EJ. Anger and hostility predict the development of atrial fibrillation in men in the Framingham Offspring Study. Circulation 2004; 109: 1267-1271.
32. Eaker ED, Sullivan LM, Kelly-Hayes M, D'Agostino RB, Benjamin EJ. Tension and anxiety and the prediction of the 10-year incidence of coronary heart disease, atrial fibrillation, and total mortality: the Framingham Offspring Study. Psychosom Med 2005; 67: 692-696.
33. Carney RM, Freedland KE, Veith RC. Depression, the autonomic nervous system, and coronary heart disease. Psychosom Med 2005; 67 (Suppl 1): S29-S33.
34. Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA, et al. Inflammation as a risk factor for atrial fibrillation. Circulation 2003; 108: 3006-3010.