Download The effects of amiodarone and early cardioversion on postoperative

The effects of amiodarone and early cardioversion on
postoperative atrial fibrillation after cardiac surgery
a
a
a
Assoc Prof. Ýlyas Atar, MD Emir Karaçaðlar, MD Süleyman Özbiçer, MD Salih Özçobanoðlu,
b
c
b
MD Assist Prof. Ayse Canan Yazici , Assoc Prof. Bahadýr Gültekin, MD , FESC, Prof Atilla Sezgin,
b
a
b
a
MD , Prof Haldun Müderrisoðlu, MD, FESC , Prof Sait Aþlamacý, MD , Prof Bülent Özin, MD
a
Department of Cardiology, Baþkent University School of Medicine, Ankara, Turkey
b
Department of Biochemistry, Baþkent University School of Medicine, Ankara, Turkey
c
Department of Biostatistics, Baskent University School of Medicine, Ankara, Turkey.
Introduction
Atrial fibrillation (AF) is the most common complication and rhythm disturbance occurring after
cardiac surgery, with its incidence in contemporary series ranging between 20% and 50% (1).
Postoperative AF is associated with an increase the risk of operative death, renal insufficiency, stroke and
prolonged hospitalization (2-4). Previously many strategies such as beta-blockers, intravenous
magnesium, sotalol, amiodarone and atrial pacing have been used to prevent AF after cardiac surgery but
still there is limited data about postoperative AF therapy after cardiac surgery when AF developed (5-7).
Current guidelines recommends ibutilide and direct current cardioversion can be use to restore sinus
rhythm in patients with postoperative AF (1).
The aim of this study was to evaluate the selective use of amiodarone and early cardioversion
postoperatively to restore normal sinus rhythm in patient with new developed AF after cardiac surgery.
Methods
Patients Population and Study Protocol
This study was a prospective, randomized, open-controlled trial. Patients with coronary artery disease
who had new onset AF longer than 30 min after cardiac surgery were considered for inclusion. Random
generated numbers table were used for randomization. Exclusion criteria were: Chronic AF, hypotension
(blood pressure lower than 90 mm Hg), and use of amiodarone prior 2 months; those in whom
amiodarone was contraindicated. The research protocol was approved by the local ethics committee of
Baþkent University. Informed consent was obtained from all patients.
Between February 2007, and October 2009, a total of 822 patients underwent cardiac surgery.
Postoperative AF longer than 30 min developed in 102 patients: 16 patients were excluded because of
prior 2 month treatment with amiodarone, 10 because of contraindications to amiodarone treatment or
cardioversion, 18 because homodynamic instability and 8 because patients or surgeons did not accept to
attend study. Thus, a total of 50 patients (mean age, 68 ± 8 years; 33 men, 17 women) fulfilling the
inclusion criteria were scheduled for the study; 26 patients were randomized to control group and 24 to
amiodarone group. Rhythm identification was obtained by 24-hour telemetry monitoring and confirmed
th
with 12-lead electrocardiography in hospital follow up. All patients questioned for AF 30 day and 12-lead
electrocardiography was obtained.
The amiodarone group received 300 mg of amiodarone bolus intravenously (IV) in 30 min and
thereafter received an IV infusion of 50 mg/hours over a 24-hour period. If NSR was established within 24
hours, then the IV infusion was discontinued and oral amiodarone therapy started. If NSR was not
established within 24 hours, then external electrical cardioversion was performed. After IV amiodarone
infusion the oral amiodarone maintained 400 mg two times a day for 5 days and 200 mg two times a day
for following 25 days.
The therapy for the control group to heart rate control included a combination of digoxine, metoprolol
or diltiazem according physician discretion and patients heart rate. If NSR was established within 24 hours,
then digoxine, beta-blockers or diltiazem was continued. If NSR was not established within 24 hours, then
external electrical cardioversion was performed. If NSR was not established after electrical cardioversion IV
amiodarone therapy was started.
th
Primer endpoints of study were NSR at 24 hours and cardioversion ratio. Secondary endpoints of
th
study were cardioversion success ratio, NSR at discharge, NSR at 30 days and crossover ratio.
Statistical Analyses
The statistical package SPSS (Statistical Package for the Social Sciences, version 11.5, SSPS Inc,
Chicago, Ill, USA) was used for statistical analyses. Continuous variables are expressed as means ±
standard deviation (median). All continuous variables checked with Kolmogorov-Smirnov normality test to
show their distributions. Continuous variables with normal distributions such as age, left ventricle
diameters, duration of intubations, levels of LDL cholesterol and potassium were compared using the
unpaired Student t test. Continuous variables with abnormal distributions such as body mass index, mean
left ventricular ejection fraction, by-pass pump time, aorta cross-clamp time, length of hospital stay,
postoperative AF beginning time, number of grafts, AF finishing time, left atrial diameter, right atrial
diameter, levels of fasting blood glucose, haemoglobin, creatinine and sodium were compared using the
Mann-Whitney U test. For categorical variables, the chi-square test was used. Values for P less than 0.05
were considered statistically significant.
Table 1. Demographic and clinical characteristics of patients
Control group
n = 26
Amiodarone
group n = 24
P value
68.6±8.2 (67)
67.4±8.5 (69)
0.601
27.9±3.6 (27.4)
27.1±4.3 26.0)
0.332
16 (61.5)
17 (70.8)
0.559
SAP, n (%)
7 (26.9)
10 (41.7)
0.373
USAP/NSTEMI, n (%)
15 (57.7)
10 (41.7)
0.396
Atypical angina, n (%)
1 (3.8)
1 (4.2)
1.0
Others, n (%)
3 (11.5)
3 (12.5)
1.0
25 (96.2)
22 (91.7)
13 (50)
Smoking, n (%)
Dyslipidemia, n (%)
Age, year
Body mass index, kg/m2
Male, n (%)
Clinics of patients previous CABG
Results
Discussion
Baseline clinical, laboratory and echocardiograhic
characteristics of both groups were similar (Table 1).
Cardiac surgery operation properties were similar in the two
groups and most of the patients undergone coronary artery
by-pass graft surgery (Table 2).
Atrial arrhythmias especially AF is the most common complication encountered after cardiac surgery. The risk
factors of postoperative AF were advanced age, previous history of AF, male gender, left ventricular systolic
dysfunction, left atrial enlargement, valvular heart surgery, chronic obstructive pulmonary disease, chronic renal
failure, diabetes mellitus, rheumatic heart disease and obesity (10). Previously beta-blockers, amiodarone, biatrial
pacing, statins, magnesium and steroid were shown to be effective prevention of AF after cardiac surgery (57,10). Conventional treatment strategies are similar other AF patients include prevention of thromboembolic
events, control of the ventricular rate response, and restoring/ maintaining sinus rhythm in patient with AF after
cardiac surgery. In one study, ibutilide was more effective than placebo for treatment of postoperative AF (8).In a
retrospective study, Samuels et al. (9) showed that amiodarone and early cardioversion was more effective than
non-amiodarone therapies with regard to restoring NSR for patients in patient with AF after elective cardiac
surgery.
Table 2. Surgical data
Control group
n = 26
Amiodarone
group n = 24
P
value
Per-operative ß-blocker, n (%)
20 (76.9)
18 (75)
1.0
0.602
Per-operative ACEI or ARB, n (%)
21 (80.8)
15 (62.5
0.211
10 (41.7)
0.584
Per-operative statin, n (%)
12 (46.2)
13 (54.2)
0.778
15 (57.7)
15 (62.5)
0.779
Operation type
19 (73.1)
17 (70.8)
1.0
24 (92.3)
19 (79.2)
0.239
History of previous MI, n (%)
13 (50)
7 (29.2)
0.159
2 (7.7)
5 (20.8)
0.239
COPD, n (%)
2 (7.7)
3 (12.5)
0.661
Number of grafts/patient
3.2±1.2 (3)
2.9±1.4 (3)
0.477
0
2 (8.3)
0.225
Bypass pump time, min
89±32 (75)
85±41 (77)
0.621
4 (15.4)
4 (16.7)
1.0
Aorta cross-clamp time, min
43±26 (39)
56±37 (45)
0.354
Monitor follow up duration, min
121±90 (98)
104±37 (96)
0.938
Length of hospital stay, day
10.3±5.4 (7.5)
8.7±2.8 (8.5)
0.739
Intubations length, hour
16.9±8.1 (15)
13.9±6.7 (12.5)
0.167
Postoperative AF beginning duration, hours
59±48 (48.5)
59±32 (48)
0.861
AF rate, beat/min
121±21 (125)
138±21 (134)
0.004
12.7±10.4 (10.5)
19.1±15.4 (15)
0.210
Hypertension, n (%)
Diabetes mellitus, n (%)
History of PAF, n (%)
History of previous PCI, n (%)
History of previous CABG, n (%)
CABG, n (%)
2 (7.7)
3 (12.5)
0.661
45.2±10.8 (43.5)
49.8±9.0 (51)
0.139
19 (73.1)
13 (54.2)
0.239
Left atrial diameter, cm
4.1±0.7 (3.9)
4.1±0.7 (4.1)
0.724
Right atrial diameter, cm
3.6±0.3 (3.6)
3.7±0.7 (3.6)
0.915
Left ventricular diameter, cm
4.8±0.7 (4.7)
5.0±0.6 (4.9)
0.349
18 (69.2)
17 (77.3)
0.746
Left ventricular ejection fraction, %
Left ventricular systolic dysfunction, n (%)
Mitral regurgitation, n (%)
CABG and valve surgery, n (%)
AF ending time, hours
Primary and secondary endpoints results were
Fasting blood glucose (mg/dL)
119±38 (111)
110±25 (105)
0.433
demonstrated Table 3. There were significantly higher NSR
Creatinine (mg/dL)
1.0±0.4 (0.9)
0.9±0.2 (0.9)
0.203
at 24th hours in amiodarone group than control group (19
LDL cholesterol (mg/dL)
117±30 (124)
114±39 (105)
0.777
patients 79.2% vs. 13 patients 50%, p=0.042).
Haemoglobin (g/dL)
12.3±2.0 (11.9)
12.4±1.8 (11.9)
0.778
Cardioversion rate were significantly higher in control group
MI: Myocardial infarction, COPD: Chronic obstructive pulmonary d isease, PAF: Paroxysmal atrial fibrillation, LDL:
than amiodarone group (p=0.019) but cardioversion
Low-Density Lipoprotein.
success rate was not different.
Cardioversion was performed to 10 patients (6 patients rhythm were converted NSR and 4 patient stayed AF) in control group and
2 patients (2 patients rhythm were converted NSR) in amiodarone group.Cardioversion was not performed 3 patients in control
group and 3 patients in amiodarone group because of the patients or surgeon discretion. Normal sinus rhythms at discharge and
30th days were similar between groups. Crossover ratio was significantly higher in control group than amiodarone group (10
patients 38.5% vs. 1 patients 4.2%, p=0.005).
All patients received amiodarone therapy according to study protocol except one patient in amiodarone group. One patient
discontinued amiodarone because of severe symptomatic bradycardia. In control group, 6 patients because of the unsuccessful
cardioversion and 4 patients because of repetitive AF attacks have to take amiodarone.
Complication rates were similar in two groups (Table 4). Two patients (7.7%) died during the study period in control group and no
patients died in amiodarone group. One of these patients died after severe stroke and the other patient died after respiratory failure
and sepsis. There were 2 (7.7%) strokes in control group and 3 (12.5%) strokes in amiodarone group. All patients with stroke were
on NSR when stroke developed and three of them on oral anticoagulant therapy.
Table 4. Complications
Table 3. Study endpoints
Control group
n = 26
Amiodarone
group n = 24
P
value
Patients with any postoperative complications, n (%)
Primary endpoints
Normal sinus rhythm at 24th hour, n (%)
Cardioversion, n (%)
Control group
n = 26
Amiodarone
group n = 24
P value
10 (38.5)
6 (26.1)
0.382
13 (50)
19 (79.2)
0.042
Death, n (%)
2 (7.7)
0
0.491
10 (38.5)
2 (8.3)
0.019
Any infection, n (%)
4 (15.4)
4 (17.4)
1.0
Renal impairment (creatinine > 2.0 mg/dL), n (%)
3 (11.5)
0
0.237
Secondary endpoints
Cardioversion success rate, n (%)
10/6 (40)
2/2 (100)
0.515
Myocardial infarction, n (%)
1 (3.8)
0
1.0
Normal sinus rhythm at discharge, n (%)
23 (88.5)
24 (100)
0.236
Stroke, n (%)
2 (7.7)
3 (12.5)
0.655
Normal sinus rhythm at 30th day, n (%)
20 (83.3)
21 (95.5)
0.349
Respiratory failure, n (%)
3 (11.5)
1 (4.3)
0.612
Crossover, n (%)
10 (38.5)
1 (4.2)
0.005
Atrio-ventricular block, n (%)
1 (3.8)
0
1.0
Study Limitations:
The sample size in the present study is relatively small, and the study is open labeled.
Conclusions
Our study is the first randomized, prospective controlled study conducted to evaluate the effect of amiodarone
and early cardioversion on postoperative AF after cardiac surgery. Amiodarone therapy seems to effective
restoring NSR at 24th hours but not at discharge and 1st month
References
1. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN,
Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S; Task Force on Practice Guidelines, American
College of Cardiology/American Heart Association; Committee for Practice Guidelines, European Society of
Cardiology; European Heart Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 guidelines for
the management of patients with atrial fibrillation-executive summary: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of
Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the
Management of Patients with Atrial Fibrillation). Eur Heart J. 2006;27:1979-2030.
2. Kalavrouziotis D, Buth KJ, Ali IS. The impact of new-onset atrial fibrillation on in-hospital mortality following
cardiac surgery. Chest 2007;131:833–9.
3. Mathew JP, Fontes ML, Tudor IC, et al. A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA
2004;291:1720 –9.
4. Villareal RP, Hariharan R, Liu BC, et al. Postoperative atrial fibrillation and mortality after coronary artery
bypass surgery. J Am Coll Cardiol 2004;43:742– 8.
5. Crystal E, Connolly SJ, Sleik K, Ginger TJ, Yusuf S. Interventions on prevention of postoperative atrial
fibrillation in patients undergoing heart surgery: a meta-analysis. Circulation. 2002;106:75-80.
6. Andrews TC, Reinmold SC, Berlin JA, Antman EM. Prevention of supraventricular arrhythmias after coronary
artery bypass surgery: a meta-analysis of randomized control trials. Circulation. 1991;84: III236-III244.
7. Burgess DC, Kilborn MJ, Keech AC. Interventions for prevention of post-operative atrial fibrillation and its
complications after cardiac surgery: a meta-analysis. Eur Heart J. 2006;27:2846-57.
8. VanderLugt JT, Mattioni T, Denker S, et al. Efficacy and safety of ibutilide fumarate for the conversion of atrial
arrhythmias after cardiac surgery. Circulation 1999;100:369 –75.
9. Samuels LE, Holmes EC, Samuels FL. Selective use of amiodarone and early cardioversion for postoperative
atrial fibrillation. Ann Thorac Surg. 2005;79:113-6.
10. Echahidi N, Pibarot P, O'Hara G, Mathieu P. Mechanisms, prevention, and treatment of atrial fibrillation after
cardiac surgery. J Am Coll Cardiol. 2008 Feb 26;51(8):793-801. Review.