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Ann Thorac Surg 1999;68:1827-1831
© 1999 The Society of Thoracic Surgeons

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Original Articles

Atrial fibrillation after operation for lung cancer: clinical and prognostic significance

^a Cardiology Unit, Istituto Europeo di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, University of Milan, Milan, Italy
^b Thoracic Surgery Division, Istituto Europeo di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, University of Milan, Milan, Italy

Address reprint requests to Dr Cardinale, Cardiology Unit, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141 Milan, Italy
e-mail: dcardinale{at}ieo.cilea.it

	Abstract

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Background. Atrial fibrillation is a common complication of early postoperative period in lung cancer thoracotomy. Its clinical incidence and short- and long-term impact on overall mortality has never been definitely assessed; moreover, it is unclear whether the arrhythmia represents an independent cardiac risk factor.

Methods. We prospectively studied 233 consecutive patients undergoing operation for lung cancer (170 with non–small-cell lung cancer). Postoperative atrial fibrillation incidence was related to different clinical factors possibly involved in its occurrence and to both short- and long-term survival.

Results. Atrial fibrillation occurred in 28 patients (12%) (same percentage in non–small-cell lung cancer); a strong relationship was observed between arrhythmia and age, history of hypertension and associated lymph node resection. The mean hospitalization time was 14 ± 4 days in patients developing atrial fibrillation and 13 ± 4 days in those who did not (p = not significant). No difference was observed between the two groups with regard to short- or long-term mortality or to long-term atrial fibrillation recurrences, also when considering the entire population and only non–small-cell lung cancer, separately.

Conclusions. At our institution, early atrial fibrillation occurrence after operation for lung cancer does not show any negative impact on short- and long-term mortality or on recurrence rate.

	Introduction

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Atrial fibrillation (AF) is a frequently occurring arrhythmia after pulmonary procedures, with reported incidences ranging from 10% to 20% after lobectomy and up to 40% after pneumonectomy [1–3]. It has been suggested that AF may be generally related to a worse prognosis and a longer postoperative hospital stay [4–7]; variability in mortality rate up to 25% has been reported in patients undergoing lung operations who experienced AF in the postoperative period [4]. Accordingly, several prophylactic antiarrhythmic treatments have been proposed in the attempt to reduce AF incidence [3, 8–11], but most of the evaluated drugs either showed modest, if any, prophylactic efficacy [3, 9, 10] or were related to a high incidence of severe adverse effects [3, 11]. Moreover, a clear link between the occurrence of AF in the postoperative period and preoperative risk factors has not yet been established; therefore, a theoretical advantage for prophylactic treatment cannot be easily identified.

In addition, it is not known whether, after conversion to sinus rhythm either by pharmacologic or electrical therapy, a long-term antiarrhythmic treatment is required to prevent AF recurrences. No previous studies have investigated whether AF postoperative occurrence may represent a marker of increased atrial vulnerability and consequent higher risk for after-discharge recurrences.

The purpose of the present study was to prospectively evaluate clinical relevance, perioperative risk factors, and long-term prognostic value of AF complicating thoracic operations for lung cancer.

	Material and methods

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We prospectively evaluated 250 consecutive patients who underwent thoracic operations for lung cancer (primary, n = 187; metastatic, n = 35; mesothelioma, n = 24; lymphoma, n = 4) in our Institute from January 1995 to June 1997. Patients with chronic AF (n = 3) and those taking antiarrhythmic therapeutic drugs, ß-blockers, or digoxin (n = 14) were excluded from the study; the final study population included 233 subjects (170 men, 63 women; mean age 59.3 ± 11 years). In 170 of 233 patients, a non–small-cell lung cancer (NSCLC) was present. Thirty-seven patients (16%) underwent pneumonectomy (10 right, 27 left), 122 (52%) lobectomy, 8 (3%) bilobectomy, 24 (10%) pleural decortication, 22 (10%) atypical lung resection, and 20 (9%) explorative thoracotomy.

Clinical cardiologic evaluation, electrocardiogram (if necessary, echocardiogram), chest roentgenogram, and pulmonary function tests were part of the preoperative assessment. After operation all patients remained in the intensive care unit for at least 24 hours under continuous electrocardiographic monitoring. In the following period, patients underwent heart rate and cardiac rhythm monitoring every 6 hours, 12-lead electrocardiogram daily, and clinical cardiologic evaluation until discharge. The pharmacologic treatment routinely used after lung operation (ie, methylxantines, adrenergic ß₂-agonists, antibiotics, and H2-antagonists) was administered to all patients according to the usual protocol.

In case of AF occurrence during the hospitalization period, amiodarone was administered intravenously in a bolus of 300 mg over 30 minutes, followed by continuous infusion of 1,200 mg over 24 hours for 2 days in all patients; in addition, digoxin was administered if necessary to reduce high ventricular rate. No prophylactic antiarrhythmic treatment was started after conversion to sinus rhythm; in case of AF recurrence, the same schedule was repeated.

After discharge, patients underwent monthly follow-up for at least 6 months (mean follow up, 18 ± 8 months) and were questioned about occurrence of symptoms possibly related to AF. Survival time was calculated for each patient from discharge until patient’s death or until end of the follow-up (December 1997).

The study was approved by our Institute’s Ethical Committee and written informed consent was obtained from each patient.

Statistical analysis
Data are reported as mean ± standard deviation. Frequencies observed in patients who experienced AF and those who did not were compared by means of a ² test and Student’s t test for unpaired data. To identify which factors predicted AF, univariate and stepwise multiple logistic regression analysis were used. A p value less than 0.05 was considered as statistically significant. The Kaplan-Meier survival analysis was used to compare the time-to-event rate between patients experiencing postoperative AF and those who did not.

	Results

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Atrial fibrillation occurred in 28 (12%) of the 233 patients who underwent thoracic operation for lung cancer and was fairly well tolerated clinically in all patients (the mean ventricular rate was 143 ± 28 beats/min and the mean systemic arterial pressure was 89 ± 15 mm Hg); a similar incidence of AF (21 of 170 patients, 12%) was found when patients with NSCLC were considered separately. The total group peak incidence was on the second postoperative day (67%), with a cumulative 82% of events occurring during the first 3 postoperative days (Fig 1).

View larger version (10K): [in this window] [in a new window]   Fig 1. Daily distribution of postoperative atrial fibrillation.

All AF patients were discharged from the hospital in stable sinus rhythm without prophylactic antiarrhythmic treatment. The mean hospitalization time was not different between patients who developed AF (14 ± 4 days) and those who did not (13 ± 4 days; p = not significant).

Preoperative and perioperative parameters of patients developing AF after thoracic operation, compared with those of patients who did not, are shown in Tables 1 and 2, respectively.

The mortality rate in the perioperative period and at the long-term follow-up (mean, 18 ± 8 months) was similar in the AF and in the no-AF groups, considering the entire study population (Fig 2) and NSCLC group (Fig 3). The total 30-day mortality rate was 1.3% (3 of 233 patients), 0.6% (1 of 170 patients) in the NSCLC population, and was related to acute myocardial infarction, respiratory insufficiency, and stroke. There were no intraoperative or 30-day postoperative deaths in the AF group. At the end of the follow-up period 23 of 28 patients (82%) in the AF group and 172 of 205 (84%) in the no-AF group were alive. In the NSCLC population the survival rate was 86% both in the AF group (18 of 21 patients) and in the no-AF group (128 of 149 patients).

View larger version (13K): [in this window] [in a new window]   Fig 2. Kaplan-Meier survival curves of patients with (AF) and without (No AF) atrial fibrillation in the early postoperative period. (NS = not significant.)

View larger version (12K): [in this window] [in a new window]   Fig 3. Kaplan-Meier survival curves of patients with non–small-cell lung cancer with (AF) and without (No AF) atrial fibrillation.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
Atrial fibrillation is a frequent complication of the postoperative course in patients undergoing thoracic operation for lung cancer [1–11]. The cause remains unclear and is almost certainly multifactorial. Hypoxia, hypovolemia, sepsis, electrolyte imbalances, augmented vagal activity, and increased cardiac load after the reduction of the pulmonary vascular bed are all well-known predisposing factors that can increase atrial vulnerability to supraventricular arrhythmias after thoracic operations, as well as in other clinical settings [12, 13]. However, previous studies showed different, sometimes contradictory, results with regard to the clinical significance of each of the abovementioned factors after noncardiac thoracic procedures [2, 5, 8, 9, 14–16].

In our study AF occurred in 28 patients (12%), an incidence observed in other studies describing a similar population [1, 4, 6]. The onset of AF was seen in most patients (67%) in the second postoperative day; the arrhythmia, because it was treated promptly, was fairly well tolerated clinically in all patients and it did not cause a prolonged hospitalization time. However, as mean hospital stay was prolonged in our institution in comparison to other hospitals [2, 5, 7]; this may have masked a difference between the two groups. In 5 of 28 patients, AF recurred a few days later and was again promptly converted to sinus rhythm by amiodarone.

Previous studies reported that antiarrhythmic drugs used for prevention of postoperative AF have not yet demonstrated an efficacy superior to their potential side effects [3, 9]. In particular, prophylactic treatment with amiodarone has been related to a higher incidence of adult respiratory distress syndrome after pneumonectomy [11].

Several factors have been considered as risk factors for the development of AF. In this, as well as in previous studies [1, 14, 17]—both in univariate and in multivariate analysis—age, hypertension, and lymph node resection were significantly associated with AF occurrence. In fact, patients who developed AF were significantly older than patients who did not and hypertension was present in 50% of patients with, and in 24% without AF. In NSCLC patients with AF the incidence of hypertension was nearly the same (52%). It is well known that age and hypertension-related cardiac structural changes, such as increased fibrous and adipose tissue in the sinoatrial node, focal interstitial deposits of amyloid in the atria, and atrial dilatation may have a significant role in the genesis of the arrhythmia [18, 19].

Other risk factors described in previous studies, such as the extent of pulmonary resection, right versus left lung resection, surgical staging for lung cancer, standard pulmonary lung function test impairment, preoperative irradiation or chemotherapy, and history of atrial arrhythmias, coronary artery disease, or heart failure [1–3, 20–22] were not observed in our study. In addition, there was no correlation between AF and intra- and postoperative characteristics, such as operation time, prolonged ventilation time, impaired arterial blood gas levels, electrolyte imbalance, blood loss, fluid balance, or postoperative complication incidence.

Although the extent of pulmonary resection was not clearly related to the onset of the arrhythmia, we found a significant relationship between associated lymph node resection and AF occurrence. It is reasonable to hypothesize that operative manipulation of autonomic nerve fibers at the pulmonary hilum may play a role at least in the earlier episodes of AF.

In some studies, AF occurrence or recurrence [1] was associated with both short- and long-term increased morbidity and mortality [4–6] and with prolonged hospitalization time [5]. Up to 25% mortality rate has been reported by Krowka and colleagues [4] in patients developing AF after pneumonectomy. In contrast, other investigators did not find the same correlation [14].

We did not find differences in survival rate between patients who developed AF and those who did not, both in the early postoperative and in the long-term follow-up period. Likewise, no differences were found when NSCLC patients were analyzed independently. This is in contrast with the results of Amar and associates [6], who, in a population of 78 patients with NSCLC, reported that early supraventricular tachydysrhythmia (SVT) was associated with poor long-term survival. In comparing the patients’ characteristics in the two studies, it is noteworthy that our NSCLC population had a favorable preoperative surgical staging (UICC I-II 87%) and consequently, a better survival rate (86%) than that of Amar and colleagues [6] (UICC I-II 37%, survival rate 48%). The difference in surgical staging is more evident in both studies if only patients with postoperative arrhythmias are considered (UICC I-II 90% versus 20%). In particular, SVT developed in most (80%) of the patients in the study by Amar and colleagues [6] who had stage III or IV disease; on the other hand, in the group without SVT, only 60% of the patients had stage III or IV. In contrast, in our population, the percentage of stage III or IV was similar in the two groups (10% and 13%, respectively). It seems reasonable to hypothesize that the observed differences in survival rate between the two studies, as well as those between the SVT and the no-SVT groups in the study by Amar and colleagues [6], could be related more to the severity in lung cancer staging than in arrhythmia occurrence. This underlines the concept that AF after thoracic operation for lung cancer has no impact on prognosis.

In conclusion, frequently AF complicates the postoperative course of elderly and hypertensive patients undergoing lung cancer operations, particularly when associated with lymph node resection. However, the arrhythmia, when promptly treated, is always fairly well tolerated and not related to short- or long-term higher mortality rates or to higher recurrence rates.

The observation that long-term follow-up, particular to the present investigation, did not disclose any prognostic negative factors related to early postoperative AF, enhances the interpretation of the only transient clinical relevance of arrhythmia.

	Acknowledgments

 
We express our gratitude to Dr Patrick Maisonneuve and Dr Peter Boyle of the Istituto Europeo di Oncologia, Division of Epidemiology and Biostatistics, for assistance with the statistical analysis.

	Footnotes

 
This article has been selected for the open discussion forum on the STS Web site: http://www.sts.org/section/atsdiscussion/

	References

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