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Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer?
HLC 2441 1–7
ORIGINAL ARTICLE
Heart, Lung and Circulation (2017) xx, 1–7 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2017.06.729
Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer?
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Q2 Ege University, School of Medicine, Department of Thoracic Surgery, Izmir, Turkey Received 15 April 2017; received in revised form 28 May 2017; accepted 23 June 2017; online published-ahead-of-print xxx
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Onder Kavurmaci, MD, Tevfik Ilker Akcam, MD *, Ayse Gul Ergonul, MD, Kutsal Turhan, MD, Alpaslan Cakan, MD, Ufuk Cagirici, MD
Background
Atrial fibrillation (AF) is a type of cardiac arrhythmia which is commonly seen following lung resection. There is currently no algorithm which can predict which patients will develop postoperative AF (PAF). The present study aims to identify the risk factors for the development of PAF and high-risk patients with PAF along with multiple risk factors.
Materials and Methods
A total of 887 patients, who underwent lung resection due to primary lung malignancy at our clinic between January 2000 and December 2016, were retrospectively analysed. Group 1 (n = 44) consisted of the patients who developed PAF and Group 2 (n = 843) consisted of the patients without PAF. Age and sex of the patients, comorbidities, previous diagnosis of malignancy, and surgery-related variables were evaluated using statistical methods for their effects on the development of AF. A score was assigned to each identified risk factor and scores of the patients were calculated. The risk of developing PAF was evaluated based on this scoring system.
Results
We found that 60 years of age and the diagnosis of chronic obstructive pulmonary disease (COPD) were significant risk factors for the development of PAF (p < 0.05). The risk of developing PAF was not associated with male sex, previous history of malignancy, presence of comorbidities, and the type of surgery applied. There was an increased risk of AF with increasing scores in the risk calculation system.
Conclusion
Advanced age and the presence of COPD were found to be associated with an increased risk of developing PAF. In addition we found a significant increase in the risk of developing PAF in the presence of multiple factors, although they did not reach statistical significance alone.
Keywords
Lung cancer surgery Postoperative atrial fibrillation Risk calculation system
Introduction Q5
Atrial fibrillation (AF) is a frequent cardiac complication following pulmonary resection [1]. Although previous studies have shown varying prevalence rates, the rate of AF has
been reported to be 12.3% following non-cardiac thoracic surgery [2] and to range from 10 to 25% following anatomic lung resection [2–9]. Although AF is thought to be a selflimiting condition caused by the propagation of an abnormal electrical impulse, it causes a significant increase in
Q3 *Corresponding author [2_TD$IF]at: Ege[23_TD$IF] University, Faculty of Medicine, Department of Thoracic Surgery, Izmir, Turkey. Phone number: +905386062581, Q4 Fax number: +902323904681. Email: [email protected] © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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morbidity and mortality, when left untreated [10,11]. The main risk factors identified for postoperative atrial fibrillation (PAF) include age above 60 years, male sex, Caucasion race, Stage II lung cancer, history of congestive heart failure, presence of preoperative cardiac arrhythmia, preoperative increased heart rate, previous peripheral vascular disease, chronic obstructive lung disease (COPD), bilobectomy and/or pneumonectomy, intra-pericardiac pneumonectomy, previous right-sided procedures, and intraoperative transfusion [4,5,6,7,12,13,14]. Prophylactic treatment options for PAF have been investigated and there is ongoing research on this subject to overcome this serious complication. In the present study, we aimed to investigate possible risk factors for the development of PAF using a risk score system for each identified risk factor and to identify high-risk patients with PAF along with multiple risk factors.
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Materials and Methods
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A total of 887 patients, who underwent lung resection due to primary lung malignancy at our clinic between January 2000 and December 2016, were retrospectively analysed. Patients who underwent biopsy or no additional surgical interventions other than exploratory thoracotomy, those who underwent revision surgery for reasons such as massive air drainage-haemorrhage, those with a known history of arrhythmia before surgery, and patients with a cardiac pacemaker were excluded. Patients who died in the perioperative and early postoperative period due to surgical reasons were also excluded. Demographic features of the patients, comorbidities, previous history of malignancy, surgical procedures applied, the results of histopathological examinations, complications, and length of hospital stays were recorded. Upon detection of AF, all patients underwent routine biochemical testing and chest X-ray. Cardiology consultation was also performed for all patients. Treatment of AF was provided by the cardiology clinic. The treatment involved amiodarone and addition of beta blockers in patients with rapid ventricular responses. All patients received standard lowmolecular-weight heparin (LMWH) therapy. In patients with PAF, the day of diagnosis, possible aetiologies, treatment protocols, echocardiographic findings, and cessation time of AF were recorded. The patients were divided into two groups: Group 1 (n = 44; 4.96%) consisted of the patients who developed PAF and Group 2 (n = 843; 95.04%) consisted of the patients without PAF. Comorbidities were classified under five categories: cardiac diseases, endocrinological diseases, chronic obstructive pulmonary disease (COPD), rheumatic diseases, and others which were previously diagnosed and for which the patients received ongoing treatment. A previous history of malignancy was also recorded. Operations were divided into three groups as sublobar resection, lobectomy, and pneumonectomy. No separate group was defined for the patients who underwent chest wall resection along with lung
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resection and for patients who underwent mediastinoscopy and lung resection in a single session. Initially, we investigated as to whether risk factors identified for the development of PAF in the literature were applicable to our patients in developing PAF. While scoring the risk factors, one point was assigned to male sex, two points to age over 60 years, one point to chronic heart disease, two points to COPD, one point to comorbidities, one point to previous history of malignancy, one point to anatomic lung resection (other than pneumonectomy), and two points to pneumonectomy. The total scores of all patients in Group 1 and Group 2 were calculated. A written informed consent was obtained from each patient. The study was conducted in accordance with the principles of the Declaration of Helsinki.
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[24_TD$IF]Statistical Analysis
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Statistical analysis was performed using SPSS version 21.0 software (IBM Corp., Armonk, NY, USA). Initially, all risk factors including male sex, age 60 years or over, presence of comorbidities, presence of a known additional malignancy, and anatomic resection were analysed using the Pearson’s chi-square test. In the next step, a score was assigned to each risk factor and all patients were re-analysed; the rate of PAF was calculated in patients with multiple risk factors (i.e., advanced age, history of additional malignancy, and pneumonectomy). Although the variables did not appear as a risk factor for PAF when evaluated individually, this step of the study attempted to evaluate whether coexistence of multiple risk factors in an individual patient induced the development of PAF. A p value of less than 0.05 was considered statistically significant.
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[25_TD$IF]Results Of 887 patients who underwent surgery due to primary lung cancer, 44 (4.96%) with PAF constituted Group 1 and 843 (95.0%) without PAF constituted Group 2. Thirty-eight patients (86.4%) were males and six (13.6%) were females in Group 1, while eight patients (18.2%) were aged <60 years and 36 patients (81.8%) were aged 60 years. The mean age was 64.29 5.81 (range: 50 to 73) years in Group 1. In the assessment of comorbidities, 22 patients (50%) had chronic heart disease, 11 (25%) had endocrinological diseases, 21 (47.7%) had COPD, one (2.3%) had rheumatic disease, and 13 (30%) had other comorbidities. Ten patients (27.7%) had a history of additional malignancy for which the patients received or were on therapy. Of patients in Group 1, 34 (77.2%) underwent lobectomy (12 right upper lobectomy (RUL), 10 right lower lobectomy (RLL), five left upper lobectomy (LUL), four left lower lobectomy (LLL), two middle lobectomy (RML), one right upper bilobectomy (RSBL), three patients (6.8%) underwent pneumonectomy (one right pneumonectomy and two left pneumonectomy), and seven patients (15.9%) underwent sublobar resection. Histopathological examination revealed an adenocarcinoma in
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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19 patients (43.2%), squamous-cell carcinoma in 20 patients (45.5%), small cell lung cancer in one patient (2.3%), and other types of a primary lung carcinoma in the remaining four patients (9.1%). Postoperative complications included prolonged air drainage in 11 (25%), replacement of blood or blood products in three (6.8%), cardiac complications other than atrial fibrillation in four (9.1%), atelectasis requiring bronchoscopy in two (4.5%), wound site infection in the early postoperative period in one (2.3%), and other complications in three patients (6.8%). The mean length of hospital stay in the postoperative period was 10.84 4.57 (range: 5 to 26) days in Group 1 (Table 1). In Group 1, PAF was detected within 24 hours in 32 (72.72%), on Day 1 in five (11.36%), on Day 2 in three (6.81%), and on Day 4 in four patients (9.09%). Further investigations to find out the aetiology of AF revealed haemorrhage requiring replacement in three, electrolyte imbalance in two, morphine toxicity in one, and retention of
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secretions in two patients. The aetiology of PAF was unable to be identified in the remaining 36 patients (81.81%). In addition, of patients who were evaluated by a cardiologist, 32 (72.72%) underwent bedside echocardiography, 22 had partial left ventricular diastolic dysfunction, six had firstdegree valvular insufficiency, and three patients had second-degree valvular insufficiency. Sinus rhythm was achieved with treatment within the first 24 hours in 37 patients (84.1%), on Day 2 in two patients (4.5%), on Day 3 in two patients (4.5%), and at on Day 4 in one patient (2.3%). Sinus rhythm was unable to be achieved in two patients (4.5%), suggesting paroxysmal AF. All patients were evaluated by a cardiologist before discharge and maintenance treatment was arranged individually. No other complication secondary to AF during hospitalisation developed in any of the patients. Statistical analysis showed a p value of 0.934 for male sex, 0.023 for age 60 years and over, 0.894 for presence of a
Table 1 Demographic data of the patients. [2_TD$IF]Group 1 Sex [3_TD$IF]Age
[4_TD$IF]Comorbidities
[5_TD$IF]Previous diagnosis of malignancy [7_TD$IF]Type of operation
[8_TD$IF]Result of pathological examination
%
Group 2
%
Total
Male
38
86.36
687
81.5
Female
6
13.63
156
18.5
725 162
Number of patients aged <60 years
8
18.18
384
45.6
392
81.81
459
54.4
495
Number of patients aged 60 years
36
Mean age
64.29
Cardiac
22
50
323
38.3
345
Endocrinological COPD
11 21
25 47.72
187 118
22.2 14
198 139
Rheumatic
1
2.27
13
1.5
14
Other
13
29.6
208
24.7
221
[6_TD$IF]Yes
10
27.72
154
18.2
164
No
34
77.2
689
81.8
723
Right upper lobectomy
12
27.27
187
22.2
199
Right middle lobectomy
2
4.54
28
3.32
30
Right lower lobectomy Right upper bilobectomy
10 1
22.72 2.27
116 19
13.8 2.25
126 20
Right lower bilobectomy
0
0
16
1.9
16
Left upper lobectomy
5
11.36
112
13.2
117
60.65
60.83
Left lower lobectomy
4
9.1
94
11.2
98
Right pneumonectomy
1
2.27
14
1.7
15
Left pneumonectomy
2
4.54
31
3.7
33
Total lobectomy
34
77.3
572
67.9
606
Total pneumonectomy Sublobar resection
3 7
6.81 15.9
45 226
5.33 26.8
48 233
[9_TD$IF]Adenocarcinoma
19
43.2
409
48.6
428
Squamous-cell carcinoma
20
45.5
251
29.9
271
Carcinoid tumour
0
0
38
4.5
38
Small-cell carcinoma
1
2.27
25
3
26
Other
4
9.1
120
14.2
[10_TD$IF]Mean length of hospital stay
[1_TD$IF]10.84/days
8.55/days
124 8.66/days
Abbreviations: COPD, chronic obstructive pulmonary disease.
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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Table 2 P values calculated according to the risk factors. [12_TD$IF]Group 1 Sex
Group 2
p
Male
Female
Male
Female
38
6
687
156
0.934
[3_TD$IF]Age
60 years
<60 years
60 years
<60 years
0.013
[13_TD$IF]Comorbid cardiac disease
36 [14_TD$IF]Yes
8 No
459 Yes
384 No
0.894
22
22
323
520
[13_TD$IF]Comorbid endocrinological disease
[14_TD$IF]Yes
No
Yes
No
11
33
187
656
[14_TD$IF]Yes
No
Yes
No
1
43
13
830
[15_TD$IF]COPD
Yes
No
Yes
No
0.00
[13_TD$IF]Comorbid other disease
21 [14_TD$IF]Yes
23 No
118 Yes
725 No
0.676
13
31
208
635
[13_TD$IF]Comorbid rheumatic disease
[16_TD$IF]History of additional malignancy
0.985 0.957
[6_TD$IF]Yes
No
Yes
No
10
34
154
689
Yes
No
Yes
No
7
37
226
617
[18_TD$IF]Lobectomy
Yes
No
Yes
No
0.075
[19_TD$IF]Pneumonectomy
34 Yes
10 No
572 Yes
271 No
0.199
3
41
45
798
[17_TD$IF]Sublobar resection
0.423 0.183
Abbreviations: COPD, chronic obstructive pulmonary disease.
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cardiologic disease, 0.985 for presence of an endocrinological disease, 0.957 for the presence rheumatic disease, less than 0.05 for the presence of COPD, 0.676 for the presence of other comorbid conditions, 0.423 for previous history of malignancy, 0.183 for sublobar resection, 0.075 for lobectomy, and 0.199 for pneumonectomy. Only age 60 years and over and COPD were found to be statistically significant risk factors (p < 0.05) (Table 2). As only two factors were identified as significant risk factors when all factors were analysed individually, a scoring system was developed with the assumption that coexistence of more than two factors might increase the risk of developing PAF (Table 3). The patients were, then, re-evaluated with the lowest score being ‘‘0” points and highest score being ‘‘10” points. Using this scoring system, six patients achieved 0 points, 52 patients achieved one point, and none of these patients developed PAF. Postoperative AF was observed in one of 168 patients who achieved two points (0.6%), two of 142 patients who achieved three points (1.4%), five of 174 patients who achieved four points (2.9%), 10 of 139 patients who achieved five points (7.2%), 12 of 128 patients who achieved six points, eight of 54 patients who achieved seven points (14.9%), four of 16 patients who achieved eight points (25%), and two of eight patients who achieved nine points (25%). No patient achieved 10 points (Figure 1).
Only 44 of 887 patients (4.96%) developed PAF, while 36 of 345 patients who achieved five points or higher developed PAF (10.4%), and the rate of PAF increased with increasing risk scores. Finally, 36 of 45 patients (81.8%) who developed PAF were those who achieved five points or higher using this scoring system (Figure 1).
Table 3 Risk factors and ‘‘scorecard”. Risk factors
Score
Patient’s score
Male sex
1
x
Comorbid cardiac disease Comorbid other disease
1 1
x x
Additional malignancy
1
x
Age 60 years and over
2
x
COPD
2
x
Lobectomy [20_TD$IF]– Pneumonectomy
12
x
Available max score
10
x
Total patients score
7
8
PAF possibility
<%15
%25
Abbreviations: COPD, chronic obstructive pulmonary disease; PAF, postoperative atrial fibrillation.
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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[1_TD$IF]Figure 1 Score distribution and score-PAF relationship.
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Discussion
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Several studies in the literature have reported variable rates of AF following lung resection [1,3,6,9,15]. In the present study, the rate of PAF was 4.96%. Strict exclusion criteria employed in this study might have also contributed to this outcome. Many studies in the literature have also emphasised the role of COPD and advanced age, which were also found to increase the incidence of PAF in the present study [2,5,6,7,11,16]. Garner et al. [15] reported advanced age and postoperative infections as the only factors affecting the development of PAF, and they reported no association with male sex, ischaemic heart disease, degree of resection (lobectomy-pneumonectomy), or surgical approach (thoracotomy-videothoracoscopy). Although many studies have reported an increase in the risk of developing PAF, there is a discrepancy in the reported age range. Onaitis et al. [6] reported an increased risk with every 10-year increment in the age; however no cut-off value for age has been identified. Mansour et al. [17] evaluated 323 patients that underwent pneumonectomy procedure and they showed an increased risk of PAF in association with age 70 years and over in univariate analysis. Supporting the findings of this study, Vaporciyan et al. [10] reported an association between age 70 years and increased risk of developing PAF. Amar et al. [5] evaluated a series of 527 patients that underwent thoracic surgery and they found a significant relationship between the risk of PAF and being 60 years or older. In the present study, which included 44 patients with PAF, the mean age was 64.29 5.81 years (50–73 years) and 60.65 10.08 years (22–84 years) in Group 2. Although there was a four-year difference in the mean values of the two groups, age 60 years or over was significantly associated with the development of AF. The presence of COPD was found to be another factor increasing the risk of developing PAF. The results are
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consistent with those of Sekine et al. [7] who reported on 244 patients that underwent surgery due to non-small cell lung cancer. In their study, 76 patients developed supraventricular tachycardia and of these patients, 58 were found to have PAF. Their statistical analysis revealed that presence of COPD was the most important risk factor triggering the development of PAF. The present study found no statistically significant relationship between the extensiveness of resection and development of PAF. This finding contradicts most studies in the literature. Onaitis et al. [6] reported that the risk of developing PAF increased with increasing extensiveness of surgery. Two different studies reported in 2001 by Rena et al. [14] and Skine et al. [7] have also reported similar findings. Lack of a significant relationship in the present study can be explained by a higher number of patients that underwent sublobar resection in view of a lower number of patients that underwent pneumonectomy. The study by Park et al. [4] published in 2007, which compared patients undergoing lung resection using thoracotomy-videothoracoscopic approach, reported no significant difference between the two groups. Time to onset of PAF was also different than those reported in the literature. The onset of PAF was most commonly at Day 2 in the studies by Rena et al. [14] and Amar et al. [11], while Marco et al. [1] reported that PAF occurred a mean 3.7 1.8 days after surgery and this duration was reported to be 3.55 days in the study by Garner et al. [15]. Onaitis et al. [6] reported that PAF most commonly occurred at 69 hours (94 84 hours) after surgery. In the present study, PAF occurred within the first 24 hours in 72.72% of the patients. The risk of developing PAF seems to have decreased with increasing time after surgery. It seems reasonable to suggest that AF mostly occurs in the early postoperative period when the patients are exposed to highest level of surgical stress. Sinus rhythm was achieved within 24 hours in 37 of 44 patients (84.1%) who received therapy after detection of PAF. Only two patients (4.5%) failed to achieve sinus rhythm
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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during the hospitalisation period and these were later discharged assuming that these patients had paroxysmal AF. Sinus rhythm was established in the remaining 42 patients. The mean postoperative length of hospital stay was 2.29 days longer in patients with AF. This finding is also consistent with the literature data. Vaporciyan et al. [2] reported longer hospital stay, higher mortality rates and higher hospitalisation costs in patients who developed AF. Similarly, there are studies reporting an increased length of hospital stay to a variable extent and higher mortality rates in patients developing PAF [7,8,9,16]. Another interesting finding in the present study is the low rate of PAF, although no prophylactic therapy was provided in any patients. The studies in the literature suggest that various therapies have been attempted with variable degrees of success in PAF prophylaxis. Many studies have been conducted on the use of drugs such as dexamethasone, amiodarone, metoprolol, and landiolol. Prophylactic therapy with metoprolol or losartan administered immediately after lung cancer surgery in patients with high n-terminal prohormone of brain natriuretic peptide (NT-proBNP) has been shown to reduce development of postoperative atrial fibrillation dramatically [6]. Similarly, amiodarone therapy initiated in the perioperative period and continued in the postoperative period was found to reduce the incidence of PAF considerably [18]. However, preoperative dexamethasone administration and perioperative landiolol infusion did not change the outcomes [8,19,20]. In a study published in 2016, Aoyama et al. [20] compared perioperative landiolol infusion with saline infusion in the control group and reported no significant difference between the two groups with respect to the development of PAF. In 2017, Zhao et al. [21] published the analysis of a pooled data of 22 studies and they concluded that the use of b-blocker, angiotensin converting enzyme inhibitor, amiodarone, magnesium or calcium channel blocker provided effective prophylactic therapy against PAF and b-blockers has emerged as the most potent agent. In a prospective and randomised clinical study by Cardinale et al. [18] published in 2016, prophylaxis therapy with metoprolol and losartan was administered to patients with elevated NT-proBNP levels in the preoperative and early postoperative period before lung cancer surgery and they reported a significant reduction in the incidence of PAF. Riber et al. [19] reported a 23% decrease in the incidence of PAF in patients who received intravenous amiodarone 300 mg for the duration of 20 minutes before surgery and continued amiodarone 600 mg peroral twice daily in the postoperative period. Prophylactic therapy was not administered to the current study patients. We suggest that the proposed scoring system may enable early detection of patients at high risk of developing PAF and prophylactic therapy can be given in appropriate patients. This study confirms that advanced age and presence of COPD increase the risk of developing PAF in patients undergoing lung resection due to primary lung cancer. Therefore, we concluded that, although factors may not show a significant relationship when evaluated
individually, co-existence of the same risk factors in a particular patient results in an increased risk of developing PAF. The rate of PAF showed a significant increase with increasing total score in this scale. The rate of PAF was 0.6% in patients achieving one point, while the rate of developing PAF was 7.2% in patients scoring five and 14.9% in patients scoring seven points in the scale. There was a significant increase in PAF detection rate among patients with a score of five or higher and the rate has reached to 25% in patients achieving a score of eight or nine points. Although there are studies in the literature that attempted to predict the risk of stroke in patients with AF, there is no scoring system to calculate the risk of developing PAF following lung surgery. We also consider that further analysis on a larger scale can establish an algorithm detecting the risk of developing PAF in patients undergoing surgery due to lung cancer. In addition to sex, age, and previous history of malignancy that were evaluated in the present study, this putative algorithm might also include other factors such as echocardiography data, increased NT-proBNP levels, and preoperative history of arrhythmia that were associated wtih increased risk in other studies. In this study, we aimed to create a scoring system that predicts the risk of developing atrial fibrillation in patients undergoing lung cancer surgery. While creating this system, we used literature information about atrial fibrillation, our clinical experience and the analysis of the data in this study group. As a result, we tried to develop a scoring system that would allow PAF development to be predicted. The variables we use are the major factors in the development of PAF, but it is possible to increase the number of these variables. We believe that this study is a pioneering work, because there are restrictive factors such as the single centred execution of the study, low number of patients and retrospective management of the study. We think that our scoring system can be supported by prospective studies and can be modified with additional parameters to make it more accurate. In conclusion, based on our study findings, we believe that this scoring system would provide guidance in selecting patients to prophylactic therapy and pave the way for the development of a new algorithm.
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Declaration of Conflicting Interests
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The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
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Funding
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The authors received no financial support for the research and/or authorship of this article. The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.
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Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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[1] Marco A, Valbona T, Daniele D, Tiziano G, Susanna S, Erino AR, et al. Left atrial size predicts the onset of atrial fibrillation after major pulmonary resections. Eur J Cardiothorac Surg 2012;41:1094–7. [2] Vaporciyan AA, Correa AM, Rice DC, Roth JA, Smythe WR, Swisher SG, et al. Risk factors associated with atrial fibrillation after non cardiac surgery: analysis of 2588 patients. J Thorac Cardiovasc Surg 2004;127: 779–86. [3] Mark FB, Thomas AA, Mark WO. Use of Amiodarone after Major Lung Resection. Ann Thorac Surg 2014;98:1199–206. [4] Park BJ, Zhang H, Rusch VW, Amar D. Video-assisted thoracic surgery does not reduce the incidence of postoperative atrial fibrillation after pulmonary lobectomy. J Thorac Cardiovasc Surg 2007;133:775–9. [5] Amar D, Zhang H, Leung DH, Roistacher N, Kadish AH. Older age is the strongest predictor of postoperative atrial fibrillation. Anesthesiology 2002;96:352–6. [6] Onaitis M, D’Amico T, Zhao Y, O’Brien S, Harpole D. Risk factors for atrial fibrillation after lung cancer surgery: analysis of the Society of Thoracic Surgeons general thoracic surgery database. Ann Thorac Surg 2010;90:368–74. [7] Sekine Y, Kesler K, Behnia M, Brooks-Brunn J, Sekine E, Brown JW. COPD may increase the incidence of refractory supraventricular arrhythmias following pulmonary resection for non-small lung cancer. Chest 2001;120:1783–90. [8] Rozencwajg S, Desthieux C, Ynineb Y, Fulgencio JP, Bonnet F. The risk of atrial fibrillation after pneumonectomy is not impaired by preoperative administration of dexamethasone. A cohort study. Anaesth Crit Care Pain Med 2017. http://dx.doi.org/10.1016/j.accpm.2016.04.005. [9] Berry MF, D’Amico TA, Onaitis MW. Use of amiodarone after major lung resection. Ann Thorac Surg 2014;98:1199–206. [10] Polanczyk CA, Goldman L, Marcantonio ER, Orav EJ, Lee TH. Supraventricular arrhythmia in patients having noncardiac surgery: clinical correlates and effect on length stay. Ann Intern Med 1998;129:279–85.
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[11] Taylor GJ, Malik SA, Colliver JA, Dove JT, Moses HW, Mikell FL, et al. 411 Usefulness of atrial fibrillation as a predictor of stroke after isolated 412 coronary artery bypass grafting. Am J Cardiol 1987;60:905–7. 413 [12] Brathwaite D, Weissman C. The new onset of atrial arrhythmias follow414 ing major noncardiothoracic surgery is associated with increased mor415 tality. Chest 1998;114:462–8. 416 [13] Passman RS, Gingold DS, Amar D, et al. Prediction rule for atrial fibril- Q10 417 lation after major noncardiac thoracic surgery. Ann Thorac Surg 2005; 418 79:1698–703. 419 [14] Rena O, Papalia E, Oliaro A, et al. Supraventricular arrhythmias after 420 resection surgery of the lung. Eur J Cardiothorac Surg 2001;20:688–93. 421 [15] Garner M, Routledge T, King JE, Pilling JE, Veres L, Harrison-Phipps K, 422 et al. New-onset atrial fibrillation after anatomic lung resection:predic423 tive factors, treatment and follow-up in a UK thoracic centre. Interact 424 Cardiovasc Thorac Surg 2017;24:260–4. 425 [16] Onaitis M, D’Amico T, Zhao Y, O’Brien S, Harpole D. Risk factors for 426 atrial fibrillation after lung cancer surgery: analysis of the Society of 427 Thoracic Surgeons general thoracic surgery database. Ann Thorac Surg 428 2010;90:368–74. 429 [17] Mansour Z, Kochetkova EA, Santelmo N, Meyer P, Wihlm JM, Quoix E, 430 et al. Risk factors for early mortality and mobidity after pneumonectomy: 431 a reappraisal. Ann Thorac Surg 2009;88:1737–43. 432 [18] Cardinale D, Sandri MT, Colombo A, Salvatici M, Tedeschi I, Bacchiani G, 433 et al. Prevention of Atrial Fibrillation in High-risk Patients Undergoing 434 Lung Cancer Surgery: The PRESAGE Trial. Ann Surg 2016;264:244–51. 435 [19] Riber LP, Christensen TD, Jensen HK, Hoesjsgaard A, Pilegaard HK. 436 Amiodarone significantly desreases atrial fibrillation in patients under437 going surgery for lung cancer. Ann Thoracic Surg 2012;94:339–44. 438 [20] Aoyama H, Otsuka Y, Aoyama Y. Landiolol infusion during general 439 anesthesia does not prevent postoperative atrial fibrillation in patients 440 undergoing lung resection. Gen Thorac Cardiovasc Surg 2016;64:735–41. 441 [21] Zhao BC, Huang TY, Deng QW, Liu WF, Liu J, Deng WT, et al. Prophy442 laxis Against Atrial Fibrillation After General Thoracic Surgery: Trial 443 Sequential Analysis and Network Meta-Analysis. Chest 2017;151:149–59. 444
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ORIGINAL ARTICLE
Heart, Lung and Circulation (2017) xx, 1–7 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2017.06.729
Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer?
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Q2 Ege University, School of Medicine, Department of Thoracic Surgery, Izmir, Turkey Received 15 April 2017; received in revised form 28 May 2017; accepted 23 June 2017; online published-ahead-of-print xxx
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Onder Kavurmaci, MD, Tevfik Ilker Akcam, MD *, Ayse Gul Ergonul, MD, Kutsal Turhan, MD, Alpaslan Cakan, MD, Ufuk Cagirici, MD
Background
Atrial fibrillation (AF) is a type of cardiac arrhythmia which is commonly seen following lung resection. There is currently no algorithm which can predict which patients will develop postoperative AF (PAF). The present study aims to identify the risk factors for the development of PAF and high-risk patients with PAF along with multiple risk factors.
Materials and Methods
A total of 887 patients, who underwent lung resection due to primary lung malignancy at our clinic between January 2000 and December 2016, were retrospectively analysed. Group 1 (n = 44) consisted of the patients who developed PAF and Group 2 (n = 843) consisted of the patients without PAF. Age and sex of the patients, comorbidities, previous diagnosis of malignancy, and surgery-related variables were evaluated using statistical methods for their effects on the development of AF. A score was assigned to each identified risk factor and scores of the patients were calculated. The risk of developing PAF was evaluated based on this scoring system.
Results
We found that 60 years of age and the diagnosis of chronic obstructive pulmonary disease (COPD) were significant risk factors for the development of PAF (p < 0.05). The risk of developing PAF was not associated with male sex, previous history of malignancy, presence of comorbidities, and the type of surgery applied. There was an increased risk of AF with increasing scores in the risk calculation system.
Conclusion
Advanced age and the presence of COPD were found to be associated with an increased risk of developing PAF. In addition we found a significant increase in the risk of developing PAF in the presence of multiple factors, although they did not reach statistical significance alone.
Keywords
Lung cancer surgery Postoperative atrial fibrillation Risk calculation system
Introduction Q5
Atrial fibrillation (AF) is a frequent cardiac complication following pulmonary resection [1]. Although previous studies have shown varying prevalence rates, the rate of AF has
been reported to be 12.3% following non-cardiac thoracic surgery [2] and to range from 10 to 25% following anatomic lung resection [2–9]. Although AF is thought to be a selflimiting condition caused by the propagation of an abnormal electrical impulse, it causes a significant increase in
Q3 *Corresponding author [2_TD$IF]at: Ege[23_TD$IF] University, Faculty of Medicine, Department of Thoracic Surgery, Izmir, Turkey. Phone number: +905386062581, Q4 Fax number: +902323904681. Email: [email protected] © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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HLC 2441 1–7
2
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O. Kavurmaci et al.
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morbidity and mortality, when left untreated [10,11]. The main risk factors identified for postoperative atrial fibrillation (PAF) include age above 60 years, male sex, Caucasion race, Stage II lung cancer, history of congestive heart failure, presence of preoperative cardiac arrhythmia, preoperative increased heart rate, previous peripheral vascular disease, chronic obstructive lung disease (COPD), bilobectomy and/or pneumonectomy, intra-pericardiac pneumonectomy, previous right-sided procedures, and intraoperative transfusion [4,5,6,7,12,13,14]. Prophylactic treatment options for PAF have been investigated and there is ongoing research on this subject to overcome this serious complication. In the present study, we aimed to investigate possible risk factors for the development of PAF using a risk score system for each identified risk factor and to identify high-risk patients with PAF along with multiple risk factors.
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Materials and Methods
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A total of 887 patients, who underwent lung resection due to primary lung malignancy at our clinic between January 2000 and December 2016, were retrospectively analysed. Patients who underwent biopsy or no additional surgical interventions other than exploratory thoracotomy, those who underwent revision surgery for reasons such as massive air drainage-haemorrhage, those with a known history of arrhythmia before surgery, and patients with a cardiac pacemaker were excluded. Patients who died in the perioperative and early postoperative period due to surgical reasons were also excluded. Demographic features of the patients, comorbidities, previous history of malignancy, surgical procedures applied, the results of histopathological examinations, complications, and length of hospital stays were recorded. Upon detection of AF, all patients underwent routine biochemical testing and chest X-ray. Cardiology consultation was also performed for all patients. Treatment of AF was provided by the cardiology clinic. The treatment involved amiodarone and addition of beta blockers in patients with rapid ventricular responses. All patients received standard lowmolecular-weight heparin (LMWH) therapy. In patients with PAF, the day of diagnosis, possible aetiologies, treatment protocols, echocardiographic findings, and cessation time of AF were recorded. The patients were divided into two groups: Group 1 (n = 44; 4.96%) consisted of the patients who developed PAF and Group 2 (n = 843; 95.04%) consisted of the patients without PAF. Comorbidities were classified under five categories: cardiac diseases, endocrinological diseases, chronic obstructive pulmonary disease (COPD), rheumatic diseases, and others which were previously diagnosed and for which the patients received ongoing treatment. A previous history of malignancy was also recorded. Operations were divided into three groups as sublobar resection, lobectomy, and pneumonectomy. No separate group was defined for the patients who underwent chest wall resection along with lung
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resection and for patients who underwent mediastinoscopy and lung resection in a single session. Initially, we investigated as to whether risk factors identified for the development of PAF in the literature were applicable to our patients in developing PAF. While scoring the risk factors, one point was assigned to male sex, two points to age over 60 years, one point to chronic heart disease, two points to COPD, one point to comorbidities, one point to previous history of malignancy, one point to anatomic lung resection (other than pneumonectomy), and two points to pneumonectomy. The total scores of all patients in Group 1 and Group 2 were calculated. A written informed consent was obtained from each patient. The study was conducted in accordance with the principles of the Declaration of Helsinki.
77 78 79 80 81 82 83 84 85 86 87 88 89
[24_TD$IF]Statistical Analysis
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Statistical analysis was performed using SPSS version 21.0 software (IBM Corp., Armonk, NY, USA). Initially, all risk factors including male sex, age 60 years or over, presence of comorbidities, presence of a known additional malignancy, and anatomic resection were analysed using the Pearson’s chi-square test. In the next step, a score was assigned to each risk factor and all patients were re-analysed; the rate of PAF was calculated in patients with multiple risk factors (i.e., advanced age, history of additional malignancy, and pneumonectomy). Although the variables did not appear as a risk factor for PAF when evaluated individually, this step of the study attempted to evaluate whether coexistence of multiple risk factors in an individual patient induced the development of PAF. A p value of less than 0.05 was considered statistically significant.
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[25_TD$IF]Results Of 887 patients who underwent surgery due to primary lung cancer, 44 (4.96%) with PAF constituted Group 1 and 843 (95.0%) without PAF constituted Group 2. Thirty-eight patients (86.4%) were males and six (13.6%) were females in Group 1, while eight patients (18.2%) were aged <60 years and 36 patients (81.8%) were aged 60 years. The mean age was 64.29 5.81 (range: 50 to 73) years in Group 1. In the assessment of comorbidities, 22 patients (50%) had chronic heart disease, 11 (25%) had endocrinological diseases, 21 (47.7%) had COPD, one (2.3%) had rheumatic disease, and 13 (30%) had other comorbidities. Ten patients (27.7%) had a history of additional malignancy for which the patients received or were on therapy. Of patients in Group 1, 34 (77.2%) underwent lobectomy (12 right upper lobectomy (RUL), 10 right lower lobectomy (RLL), five left upper lobectomy (LUL), four left lower lobectomy (LLL), two middle lobectomy (RML), one right upper bilobectomy (RSBL), three patients (6.8%) underwent pneumonectomy (one right pneumonectomy and two left pneumonectomy), and seven patients (15.9%) underwent sublobar resection. Histopathological examination revealed an adenocarcinoma in
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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HLC 2441 1–7
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19 patients (43.2%), squamous-cell carcinoma in 20 patients (45.5%), small cell lung cancer in one patient (2.3%), and other types of a primary lung carcinoma in the remaining four patients (9.1%). Postoperative complications included prolonged air drainage in 11 (25%), replacement of blood or blood products in three (6.8%), cardiac complications other than atrial fibrillation in four (9.1%), atelectasis requiring bronchoscopy in two (4.5%), wound site infection in the early postoperative period in one (2.3%), and other complications in three patients (6.8%). The mean length of hospital stay in the postoperative period was 10.84 4.57 (range: 5 to 26) days in Group 1 (Table 1). In Group 1, PAF was detected within 24 hours in 32 (72.72%), on Day 1 in five (11.36%), on Day 2 in three (6.81%), and on Day 4 in four patients (9.09%). Further investigations to find out the aetiology of AF revealed haemorrhage requiring replacement in three, electrolyte imbalance in two, morphine toxicity in one, and retention of
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secretions in two patients. The aetiology of PAF was unable to be identified in the remaining 36 patients (81.81%). In addition, of patients who were evaluated by a cardiologist, 32 (72.72%) underwent bedside echocardiography, 22 had partial left ventricular diastolic dysfunction, six had firstdegree valvular insufficiency, and three patients had second-degree valvular insufficiency. Sinus rhythm was achieved with treatment within the first 24 hours in 37 patients (84.1%), on Day 2 in two patients (4.5%), on Day 3 in two patients (4.5%), and at on Day 4 in one patient (2.3%). Sinus rhythm was unable to be achieved in two patients (4.5%), suggesting paroxysmal AF. All patients were evaluated by a cardiologist before discharge and maintenance treatment was arranged individually. No other complication secondary to AF during hospitalisation developed in any of the patients. Statistical analysis showed a p value of 0.934 for male sex, 0.023 for age 60 years and over, 0.894 for presence of a
Table 1 Demographic data of the patients. [2_TD$IF]Group 1 Sex [3_TD$IF]Age
[4_TD$IF]Comorbidities
[5_TD$IF]Previous diagnosis of malignancy [7_TD$IF]Type of operation
[8_TD$IF]Result of pathological examination
%
Group 2
%
Total
Male
38
86.36
687
81.5
Female
6
13.63
156
18.5
725 162
Number of patients aged <60 years
8
18.18
384
45.6
392
81.81
459
54.4
495
Number of patients aged 60 years
36
Mean age
64.29
Cardiac
22
50
323
38.3
345
Endocrinological COPD
11 21
25 47.72
187 118
22.2 14
198 139
Rheumatic
1
2.27
13
1.5
14
Other
13
29.6
208
24.7
221
[6_TD$IF]Yes
10
27.72
154
18.2
164
No
34
77.2
689
81.8
723
Right upper lobectomy
12
27.27
187
22.2
199
Right middle lobectomy
2
4.54
28
3.32
30
Right lower lobectomy Right upper bilobectomy
10 1
22.72 2.27
116 19
13.8 2.25
126 20
Right lower bilobectomy
0
0
16
1.9
16
Left upper lobectomy
5
11.36
112
13.2
117
60.65
60.83
Left lower lobectomy
4
9.1
94
11.2
98
Right pneumonectomy
1
2.27
14
1.7
15
Left pneumonectomy
2
4.54
31
3.7
33
Total lobectomy
34
77.3
572
67.9
606
Total pneumonectomy Sublobar resection
3 7
6.81 15.9
45 226
5.33 26.8
48 233
[9_TD$IF]Adenocarcinoma
19
43.2
409
48.6
428
Squamous-cell carcinoma
20
45.5
251
29.9
271
Carcinoid tumour
0
0
38
4.5
38
Small-cell carcinoma
1
2.27
25
3
26
Other
4
9.1
120
14.2
[10_TD$IF]Mean length of hospital stay
[1_TD$IF]10.84/days
8.55/days
124 8.66/days
Abbreviations: COPD, chronic obstructive pulmonary disease.
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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Table 2 P values calculated according to the risk factors. [12_TD$IF]Group 1 Sex
Group 2
p
Male
Female
Male
Female
38
6
687
156
0.934
[3_TD$IF]Age
60 years
<60 years
60 years
<60 years
0.013
[13_TD$IF]Comorbid cardiac disease
36 [14_TD$IF]Yes
8 No
459 Yes
384 No
0.894
22
22
323
520
[13_TD$IF]Comorbid endocrinological disease
[14_TD$IF]Yes
No
Yes
No
11
33
187
656
[14_TD$IF]Yes
No
Yes
No
1
43
13
830
[15_TD$IF]COPD
Yes
No
Yes
No
0.00
[13_TD$IF]Comorbid other disease
21 [14_TD$IF]Yes
23 No
118 Yes
725 No
0.676
13
31
208
635
[13_TD$IF]Comorbid rheumatic disease
[16_TD$IF]History of additional malignancy
0.985 0.957
[6_TD$IF]Yes
No
Yes
No
10
34
154
689
Yes
No
Yes
No
7
37
226
617
[18_TD$IF]Lobectomy
Yes
No
Yes
No
0.075
[19_TD$IF]Pneumonectomy
34 Yes
10 No
572 Yes
271 No
0.199
3
41
45
798
[17_TD$IF]Sublobar resection
0.423 0.183
Abbreviations: COPD, chronic obstructive pulmonary disease.
164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 Q8 182 183 184 185 186 187 188 189
cardiologic disease, 0.985 for presence of an endocrinological disease, 0.957 for the presence rheumatic disease, less than 0.05 for the presence of COPD, 0.676 for the presence of other comorbid conditions, 0.423 for previous history of malignancy, 0.183 for sublobar resection, 0.075 for lobectomy, and 0.199 for pneumonectomy. Only age 60 years and over and COPD were found to be statistically significant risk factors (p < 0.05) (Table 2). As only two factors were identified as significant risk factors when all factors were analysed individually, a scoring system was developed with the assumption that coexistence of more than two factors might increase the risk of developing PAF (Table 3). The patients were, then, re-evaluated with the lowest score being ‘‘0” points and highest score being ‘‘10” points. Using this scoring system, six patients achieved 0 points, 52 patients achieved one point, and none of these patients developed PAF. Postoperative AF was observed in one of 168 patients who achieved two points (0.6%), two of 142 patients who achieved three points (1.4%), five of 174 patients who achieved four points (2.9%), 10 of 139 patients who achieved five points (7.2%), 12 of 128 patients who achieved six points, eight of 54 patients who achieved seven points (14.9%), four of 16 patients who achieved eight points (25%), and two of eight patients who achieved nine points (25%). No patient achieved 10 points (Figure 1).
Only 44 of 887 patients (4.96%) developed PAF, while 36 of 345 patients who achieved five points or higher developed PAF (10.4%), and the rate of PAF increased with increasing risk scores. Finally, 36 of 45 patients (81.8%) who developed PAF were those who achieved five points or higher using this scoring system (Figure 1).
Table 3 Risk factors and ‘‘scorecard”. Risk factors
Score
Patient’s score
Male sex
1
x
Comorbid cardiac disease Comorbid other disease
1 1
x x
Additional malignancy
1
x
Age 60 years and over
2
x
COPD
2
x
Lobectomy [20_TD$IF]– Pneumonectomy
12
x
Available max score
10
x
Total patients score
7
8
PAF possibility
<%15
%25
Abbreviations: COPD, chronic obstructive pulmonary disease; PAF, postoperative atrial fibrillation.
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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[1_TD$IF]Figure 1 Score distribution and score-PAF relationship.
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Discussion
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Several studies in the literature have reported variable rates of AF following lung resection [1,3,6,9,15]. In the present study, the rate of PAF was 4.96%. Strict exclusion criteria employed in this study might have also contributed to this outcome. Many studies in the literature have also emphasised the role of COPD and advanced age, which were also found to increase the incidence of PAF in the present study [2,5,6,7,11,16]. Garner et al. [15] reported advanced age and postoperative infections as the only factors affecting the development of PAF, and they reported no association with male sex, ischaemic heart disease, degree of resection (lobectomy-pneumonectomy), or surgical approach (thoracotomy-videothoracoscopy). Although many studies have reported an increase in the risk of developing PAF, there is a discrepancy in the reported age range. Onaitis et al. [6] reported an increased risk with every 10-year increment in the age; however no cut-off value for age has been identified. Mansour et al. [17] evaluated 323 patients that underwent pneumonectomy procedure and they showed an increased risk of PAF in association with age 70 years and over in univariate analysis. Supporting the findings of this study, Vaporciyan et al. [10] reported an association between age 70 years and increased risk of developing PAF. Amar et al. [5] evaluated a series of 527 patients that underwent thoracic surgery and they found a significant relationship between the risk of PAF and being 60 years or older. In the present study, which included 44 patients with PAF, the mean age was 64.29 5.81 years (50–73 years) and 60.65 10.08 years (22–84 years) in Group 2. Although there was a four-year difference in the mean values of the two groups, age 60 years or over was significantly associated with the development of AF. The presence of COPD was found to be another factor increasing the risk of developing PAF. The results are
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consistent with those of Sekine et al. [7] who reported on 244 patients that underwent surgery due to non-small cell lung cancer. In their study, 76 patients developed supraventricular tachycardia and of these patients, 58 were found to have PAF. Their statistical analysis revealed that presence of COPD was the most important risk factor triggering the development of PAF. The present study found no statistically significant relationship between the extensiveness of resection and development of PAF. This finding contradicts most studies in the literature. Onaitis et al. [6] reported that the risk of developing PAF increased with increasing extensiveness of surgery. Two different studies reported in 2001 by Rena et al. [14] and Skine et al. [7] have also reported similar findings. Lack of a significant relationship in the present study can be explained by a higher number of patients that underwent sublobar resection in view of a lower number of patients that underwent pneumonectomy. The study by Park et al. [4] published in 2007, which compared patients undergoing lung resection using thoracotomy-videothoracoscopic approach, reported no significant difference between the two groups. Time to onset of PAF was also different than those reported in the literature. The onset of PAF was most commonly at Day 2 in the studies by Rena et al. [14] and Amar et al. [11], while Marco et al. [1] reported that PAF occurred a mean 3.7 1.8 days after surgery and this duration was reported to be 3.55 days in the study by Garner et al. [15]. Onaitis et al. [6] reported that PAF most commonly occurred at 69 hours (94 84 hours) after surgery. In the present study, PAF occurred within the first 24 hours in 72.72% of the patients. The risk of developing PAF seems to have decreased with increasing time after surgery. It seems reasonable to suggest that AF mostly occurs in the early postoperative period when the patients are exposed to highest level of surgical stress. Sinus rhythm was achieved within 24 hours in 37 of 44 patients (84.1%) who received therapy after detection of PAF. Only two patients (4.5%) failed to achieve sinus rhythm
Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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during the hospitalisation period and these were later discharged assuming that these patients had paroxysmal AF. Sinus rhythm was established in the remaining 42 patients. The mean postoperative length of hospital stay was 2.29 days longer in patients with AF. This finding is also consistent with the literature data. Vaporciyan et al. [2] reported longer hospital stay, higher mortality rates and higher hospitalisation costs in patients who developed AF. Similarly, there are studies reporting an increased length of hospital stay to a variable extent and higher mortality rates in patients developing PAF [7,8,9,16]. Another interesting finding in the present study is the low rate of PAF, although no prophylactic therapy was provided in any patients. The studies in the literature suggest that various therapies have been attempted with variable degrees of success in PAF prophylaxis. Many studies have been conducted on the use of drugs such as dexamethasone, amiodarone, metoprolol, and landiolol. Prophylactic therapy with metoprolol or losartan administered immediately after lung cancer surgery in patients with high n-terminal prohormone of brain natriuretic peptide (NT-proBNP) has been shown to reduce development of postoperative atrial fibrillation dramatically [6]. Similarly, amiodarone therapy initiated in the perioperative period and continued in the postoperative period was found to reduce the incidence of PAF considerably [18]. However, preoperative dexamethasone administration and perioperative landiolol infusion did not change the outcomes [8,19,20]. In a study published in 2016, Aoyama et al. [20] compared perioperative landiolol infusion with saline infusion in the control group and reported no significant difference between the two groups with respect to the development of PAF. In 2017, Zhao et al. [21] published the analysis of a pooled data of 22 studies and they concluded that the use of b-blocker, angiotensin converting enzyme inhibitor, amiodarone, magnesium or calcium channel blocker provided effective prophylactic therapy against PAF and b-blockers has emerged as the most potent agent. In a prospective and randomised clinical study by Cardinale et al. [18] published in 2016, prophylaxis therapy with metoprolol and losartan was administered to patients with elevated NT-proBNP levels in the preoperative and early postoperative period before lung cancer surgery and they reported a significant reduction in the incidence of PAF. Riber et al. [19] reported a 23% decrease in the incidence of PAF in patients who received intravenous amiodarone 300 mg for the duration of 20 minutes before surgery and continued amiodarone 600 mg peroral twice daily in the postoperative period. Prophylactic therapy was not administered to the current study patients. We suggest that the proposed scoring system may enable early detection of patients at high risk of developing PAF and prophylactic therapy can be given in appropriate patients. This study confirms that advanced age and presence of COPD increase the risk of developing PAF in patients undergoing lung resection due to primary lung cancer. Therefore, we concluded that, although factors may not show a significant relationship when evaluated
individually, co-existence of the same risk factors in a particular patient results in an increased risk of developing PAF. The rate of PAF showed a significant increase with increasing total score in this scale. The rate of PAF was 0.6% in patients achieving one point, while the rate of developing PAF was 7.2% in patients scoring five and 14.9% in patients scoring seven points in the scale. There was a significant increase in PAF detection rate among patients with a score of five or higher and the rate has reached to 25% in patients achieving a score of eight or nine points. Although there are studies in the literature that attempted to predict the risk of stroke in patients with AF, there is no scoring system to calculate the risk of developing PAF following lung surgery. We also consider that further analysis on a larger scale can establish an algorithm detecting the risk of developing PAF in patients undergoing surgery due to lung cancer. In addition to sex, age, and previous history of malignancy that were evaluated in the present study, this putative algorithm might also include other factors such as echocardiography data, increased NT-proBNP levels, and preoperative history of arrhythmia that were associated wtih increased risk in other studies. In this study, we aimed to create a scoring system that predicts the risk of developing atrial fibrillation in patients undergoing lung cancer surgery. While creating this system, we used literature information about atrial fibrillation, our clinical experience and the analysis of the data in this study group. As a result, we tried to develop a scoring system that would allow PAF development to be predicted. The variables we use are the major factors in the development of PAF, but it is possible to increase the number of these variables. We believe that this study is a pioneering work, because there are restrictive factors such as the single centred execution of the study, low number of patients and retrospective management of the study. We think that our scoring system can be supported by prospective studies and can be modified with additional parameters to make it more accurate. In conclusion, based on our study findings, we believe that this scoring system would provide guidance in selecting patients to prophylactic therapy and pave the way for the development of a new algorithm.
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Declaration of Conflicting Interests
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The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
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Funding
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The authors received no financial support for the research and/or authorship of this article. The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.
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Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729
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References
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Please cite this article in press as: Kavurmaci O, et al. Is the Risk of Postoperative Atrial Fibrillation Predictable in Patients Undergoing Surgery Due to Primary Lung Cancer? Heart, Lung and Circulation (2017), http://dx.doi.org/10.1016/j. hlc.2017.06.729