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Abstract

Objective

To compare the efficacy of electrical versus pharmacological cardioversion following prosthetic cardiac valve replacement in patients with permanent atrial fibrillation (AF).

Methods

Patients with permanent AF who had undergone prosthetic cardiac valve replacement, who had a cardiothoracic ratio ≤0.5 and a left atrial diameter ≤50 mm for ≥6 months after surgery were randomly divided to receive either electrical or pharmacological cardioversion. Patients in the electrical cardioversion group were given direct-current synchronized electrical defibrillation under general anaesthesia. Patients in the pharmacological cardioversion group were given oral combination therapy with amiodarone, captopril and simvastatin for 3 months.

Results

A total of 115 patients received either electrical cardioversion (n = 59) or pharmacological cardioversion (n = 56); reversion to sinus rhythm occurred in 98.3% and 26.8%, respectively. Recurrence rates were similar in the two groups (3.4% and 6.7% for electrical and pharmacological cardioversion, respectively). No deaths or severe complications were reported.

Conclusion

Electrical cardioversion has a favourable safety profile and appears to be a more effective method than pharmacological cardioversion for the treatment of permanent AF after cardiac valve replacement, once the heart has returned close to its normal size.

Keywords

Electrical cardioversion permanent atrial fibrillation pharmacological cardioversion prosthetic cardiac valve replacement

Introduction

Atrial fibrillation (AF) mostly presents in patients with organic heart disease; in China it is commonly associated with rheumatic valvular disease. Treatment of AF involves two main strategies: rate control, in which the rapid ventricular rate resulting from AF is targeted, and rhythm control, in which AF is converted to normal sinus rhythm. Conversion to (and maintenance of) sinus rhythm is particularly difficult in permanent AF, defined as AF with a duration >1 year.¹ Over 40% of patients who have undergone mitral surgery have permanent AF,² even when blood dynamics and symptoms show improvement postoperatively.^3,4

After valve replacement surgery, cardiac function gradually improves and the enlarged heart reduces in size, with the cardiothoracic ratio becoming closer to normal. Atrial pressure and left atrial diameter gradually reduce and it may then become possible to convert AF into sinus rhythm. Our experience is that the conversion rate for patients with permanent AF is higher when the heart has recovered close to its normal size after surgery (unpublished observations). A reversion rate of 39% has been reported for pharmacological cardioversion in patients with AF after valvular replacement.⁵

The present study compared sinus rhythm rates after pharmacological or electrical cardioversion after prosthetic cardiac valve replacement, in patients with permanent AF whose hearts had recovered close to normal size postoperatively.

Patients and methods

Patients

Patients aged >18 years with permanent AF, confirmed by two separate electrocardiographic examinations, who had undergone prosthetic mitral valve replacement in the Second Hospital of Lanzhou University, Lanzhou City, Gansu, China, between July 2006 and June 2012, with or without aortic valve replacement, with a cardiothoracic ratio ≤0.5 on cardiac anteroposterior X-radiography and a left atrial diameter ≤50 mm on Doppler ultrasound for ≥6 months postsurgery were included in the study. The mechanical valves used were from Medtronic (Minneapolis, MN, USA). All patients received standard long-term anticoagulant therapy with warfarin and/or digoxin following surgery. Patients with New York Heart Association heart failure class IV, a history of sick sinus syndrome or second- or third-degree atrioventricular block, severe hepatic and/or renal dysfunction, hyperthyroidism or contraindications to treatment with amiodarone were excluded from the study.

All patients gave written informed consent and the study protocol was approved by the Ethics Committee of the Second Hospital of Lanzhou University.

Cardioversion and follow up

Patients were divided randomly (using a random number table) to receive either electrical defibrillation or pharmacological therapy. All patients underwent 12-lead electrocardiography (ECG), cardiac anteroposterior X-ray, echocardiography, and measurement of haematological and biochemical parameters before treatment.

In the electrical cardioversion group, patients were first given 200 mg amiodarone three times a day for 4 days. Digoxin treatment was stopped and the dose of warfarin was reduced to give an international normalized ratio (INR) for blood clotting of 2–3. Electrical defibrillation was performed on the fifth day. Food and drink were prohibited for 6 h before the procedure. Patients were given a slow intravenous injection of 1 mg/kg propofol and were monitored continuously using 12-lead ECG. Once unconscious, patients received direct-current synchronized electrical cardioversion using an initial energy level of 200 J. If this did not succeed, up to two 300 J shocks were given. Electrical treatment was stopped if sinus rhythm was not restored within three shocks. After successful restoration of normal rhythm, 200 mg amiodarone was taken daily for 30 days. Patients were followed up every month for 6 months and then every 3–6 months thereafter.

In the pharmacological cardioversion group, patients were given 3 months’ combination therapy with oral amiodarone at a dose of 600 mg/day for 3 days, 400 mg/day for the following 3 days and then 200 mg/day, oral captopril at a dose of 12.5 mg twice a day 1 h before food, and oral simvastatin at a dose of 15 mg/day at night. Patients were evaluated every 2 weeks by 12-lead ECG. Blood clotting was monitored and the warfarin dose was adjusted to give an INR of 2–3. Any adverse effects were recorded. If sinus rhythm was restored, 200 mg amiodarone alone was then taken daily for 30 days. If there was no restoration of normal rhythm within 3 months, therapy was stopped. Patients were followed up every month for 6 months and then every 3–6 months thereafter.

Statistical analyses

Data were presented as mean ± SD for continuous variables and as frequencies for categorical variables. Differences between the two groups were examined for statistical significance the Student’s t-test for continuous variables and χ²-test for categorical variables. All statistical analyses were performed using SPSS® software, version 17.0 (SPSS Inc., Chicago, IL, USA). A P-value < 0.05 was considered to be statistically significant.

Results

Patient characteristics

A total of 115 patients with permanent AF were included in the study; of these, 75 had received prosthetic mitral valve replacement and the other 40 had received both mitral and aortic valve replacements. Following randomization, 59 patients underwent electrical cardioversion and 56 underwent pharmacological cardioversion. There were no statistically significant differences between the two groups in terms of age, sex, replaced valves, AF duration time, follow-up period, left atrial diameter, left ventricular ejection fraction or cardiothoracic ratio (Table 1). Patient randomization and outcomes are summarizd in Figure 1.

Figure 1.

Randomization and outcomes in patients with permanent atrial fibrillation, treated with direct-current (DC) electrical cardioversion or pharmacological cardioversion with amiodarone, captopril and simvastatin following prosthetic heart valve replacement.

Table 1.

Baseline characteristics of patients with permanent atrial fibrillation (AF) treated with direct-current (DC) electrical cardioversion or pharmacological cardioversion with amiodarone, captopril and simvastatin following prosthetic heart valve replacement.

Characteristic	DC electrical cardioversion n = 59	Pharmacological cardioversion n = 56
Age, years	52.8 ± 8.0	51.8 ± 10.9
Sex
Male	28	31
Female	31	25
Replaced valve
Mitral	40	35
Mitral and aortic	19	21
Time since surgery, months	10.3 ± 3.4	10.8 ± 2.9
Duration of AF, months	54.2 ± 25.9	53.5 ± 25.4
Left atrial diameter, mm	45.2 ± 3.5	45.2 ± 3.6
Left ventricular ejection fraction, %	58.6 ± 6.5	58.2 ± 6.2
Cardiothoracic ratio	0.48 ± 0.02	0.48 ± 0.02

Data presented as n patients or mean ± SD.

No statistically significant between-group differences (P ≥ 0.05), Student’s t-test or χ²-test.

Cardioversion

In the electrical cardioversion group (n = 59), one patient reverted to atrial flutter after 4 days’ treatment with amidarone, but no patient converted to sinus rhythm spontaneously. With electrical defibrillation, 50 patients converted to normal sinus rhythm after the first shock of 200 J, four converted after a shock of 200 J and then one of 300 J, and three required a second 300 J shock to convert. The patient with atrial flutter was converted to sinus rhythm using one shock of 50 J. Electrical cardioversion only failed in one patient, giving an overall immediate electrical cardioversion rate of 98.3% (Table 2).

Table 2.

Outcomes in patients with permanent atrial fibrillation treated with direct-current (DC) electrical cardioversion or pharmacological cardioversion with amiodarone, captopril and simvastatin following prosthetic heart valve replacement.

Parameter	DC electrical cardioversion n = 59	Pharmacological cardioversion n = 56	Statistical significance
Cardioversion rate	58 (98.3)	15 (26.8)	P < 0.01
Relapse rate	2 (3.4)	1 (6.7)	NS
Time to cardioversion, days	4.0 ± 0.0	41.2 ± 18.5	P < 0.01
Follow-up period, months	19.7 ± 9.2	21.3 ± 7.0	NS

Data presented as n (%) of patients or mean ± SD.

NS, not statistically significant (P ≥ 0.05), Student’s t-test or χ² test.

Immediately after cardioversion, six patients presented with transient frequent atrial premature beats, but these recovered spontaneously within 5 min. In addition, two patients with AF of 6–12 years’ duration developed sinus bradycardia with a heart rate of 43–52 beats/min. These patients were treated with isoprenaline 0.5 mg in 250 ml 5% glucose via intravenous infusion, with the infusion speed being modulated according to the heart rate; in both patients the heart rate was restored to >50 beats/min within 2 h.

In the pharmacological cardioversion group (n = 56), only 15 patients successfully converted to sinus rhythm within 3 months’ treatment: three patients converted during the first month, 10 during the second month and two in the third month, giving an overall conversion rate of 26.8% (Table 2). Two of these patients developed short-term atrial flutter, but this resolved within 72 h of treatment with 200 mg/day amiodarone.

During combination therapy, five patients presented with cough. Three of these patients had only slight symptoms and were able to continue with the complete pharmacological cardioversion regimen. However, in the other two patients the symptoms were severe; in these cases, captopril treatment was stopped and only amiodarone and simvastatin were given.

The difference in the sinus rhythm rates between the electrical and pharmacological cardioversion groups (98.3% versus 26.8%) was statistically significant (P < 0.01) (Table 2). Patients in the electrical cardioversion group converted successfully in 4.0 ± 0.0 days, whereas those in the pharmacological cardioversion group took 41.2 ± 18.5 days (P < 0.01).

Follow up

Follow up ranged between 3 and 34 months in the electrical cardioversion group and between 9 and 33 months in the pharmacological cardioversion group; the mean ± SD follow-up period was similar in the two groups (Table 2). AF recurred in two patients in the electrical cardioversion group due to heart failure caused by heavy manual labour and fluid loading, respectively. AF also recurred in one patient in the pharmacological cardioversion group, and was again associated with heart failure brought on by heavy manual labour. Recurrence of AF was successfully treated with amiodarone in all three patients. The overall relapse rates were 3.4% and 6.7% in the electrical and pharmacological cardioversion groups, respectively (Table 2); this difference was not statistically significant. No deaths or severe complications were reported in any of the 115 patients included in the study.

Discussion

Direct-current synchronized electrical reversion was first proposed by Lown⁶ in 1962 and has become the main treatment method for AF. However, in patients with severe valvular heart disease, it is difficult to convert permanent AF to sinus rhythm using synchronized electrical cardioversion, or even pharmacological cardioversion, because of cardiac hypertrophy and dysfunction. In the present study, the conversion rate was 26.8% for pharmacological cardioversion and 98.3% for electrical cardioversion, in patients with permanent AF who had undergone cardiac valvular replacement and whose cardiac function had improved to give a cardiothoracic ratio ≤ 0.5 and a left atrial diameter ≤ 50 mm. These results suggest that direct-current synchronized electrical reversion is more effective than pharmacological cardioversion in such patients. The conversion rate of 26.8% for pharmacological cardioversion in the present study is lower than the 39% reported by Qian et al.⁵ in patients receiving combination therapy for 12 months, but it is not known whether this lower rate is related to the particular population studied or to the shorter treatment period.

A number of surgical techniques are available for the treatment of AF. Following the demonstration of ‘micro re-entry circuits’ in AF, the maze procedure, in which atrial incisions prevent atrial re-entry, was developed.⁷ First performed in 1987, it has since evolved into the Cox maze III procedure.^7–10 This method is extremely complex and expensive, and is only performed in specialist hospitals. In 2005, Wolf et al.¹¹ reported a success rate of up to 91.3% using a mini-maze procedure involving video-assisted bilateral epicardial bipolar radiofrequency pulmonary vein isolation and left atrial appendage excision. Furthermore, pure pulmonary vein isolation ablation has been reported to have reversion rates in chronic AF of up to 80%.^12,13 Treatment of AF with radiofrequency ablation has delivered long-term sinus maintenance rates of 76–92%;^14,15 this technique can be used in most patients with AF, but has a high recurrence rate.¹⁶

The size of the heart appears to influence the cardioversion rate in AF. The size of the left atrium and the duration of AF have been reported to affect the long-term efficacy of radiofrequency ablation.^17,18 Pharmacological cardioversion of AF has also been reported to be dependent on left atrial size and left ventricular ejection fraction.^19,20 In the present study, only patients with permanent AF whose hearts had recovered close to normal size after prosthetic cardiac valve replacement were included.

In the present study, the conversion rate was higher with electrical than with pharmacological cardioversion. Electrical cardioversion is a simple procedure that is easy to perform, but it may not be applicable to all patients with permanent AF; in the present study it was only used in patients with a heart size close to normal. However, the optimum left atrial diameter for electrical reversion after cardiac valvular replacement is not yet known and further investigations are required. It may be possible to perform electrical reversion alone or with pharmacological cardioversion soon after surgery.

In conclusion, electrical cardioversion has a favourable safety profile; it appears to be a more effective method than pharmacological cardioversion for the treatment of permanent AF, after cardiac valve replacement, once the heart has returned close to normal size.

Footnotes

Declaration of conflicting interest

The authors declare that there are no conflicts of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References

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Comparison of pharmacological and electrical cardioversion in permanent atrial fibrillation after prosthetic cardiac valve replacement: A prospective randomized trial

Abstract

Objective

Methods

Results

Conclusion

Keywords

Introduction

Patients and methods

Patients

Cardioversion and follow up

Statistical analyses

Results

Patient characteristics

Cardioversion

Follow up

Discussion

Footnotes

Declaration of conflicting interest

Funding

References