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Interact CardioVasc Thorac Surg 2008;7:1039-1042. doi:10.1510/icvts.2008.181099 © 2008 European Association of Cardio-Thoracic Surgery
Incidence of atrial fibrillation after extrapleural pneumonectomy vs. pleurectomy in patients with malignant pleural mesothelioma
a Department of Surgery, St Vincent Medical Center, New York Medical College, School of Medicine, 170 West 12th Street, New York, NY 10011, USA Received 2 April 2008; received in revised form 28 May 2008; accepted 29 May 2008
Corresponding author: Tel.: +212-604-7000.
Extrapleural pneumonectomy (EPP) and pleurectomy are the surgical procedures for the treatment of pleural mesothelioma. However, EPP increases the risk for postoperative atrial fibrillation (AF). We conducted a retrospective chart review of 130 patients who underwent EPP or pleurectomy. Seventy patients (excluding three patients with a prior history of AF) underwent EPP and 57 patients underwent pleurectomy. The mean ages were 60±11 and 63±13 years, and the male to female ratios were 50/20 and 44/13, respectively. Postoperative AF was observed in 45 patients with 36 (51%) of these cases occurring after EPP and 9 (17%) after pleurectomy (P<0.0001). There were no significant differences between the two treatment groups for gender, age, side of affected lung, preoperative heart rate, history of beta-blocker use, coronary heart disease, and chronic obstructive pulmonary disease. Through logistic regression, EPP (OR=7.1, 95% CI: 2.9, 17.8) and age over 65 years (OR=2.9, 95% CI: 1.2, 6.8) were found to be risk factors for AF. We conclude that EPP vs. pleurectomy and age over 65 years are risk factors for postoperative AF. The increased odds of having AF after EPP could be due to right heart stress caused by pneumonectomy.
Key Words: Right heart stress; Extrapleural pneumonectomy; Pleurectomy; Atrial fibrillation
Thoracic surgery remains a high-risk procedure for many patients, and atrial fibrillation (AF) is the most frequent complication with the highest morbidity rates in this patient population [1, 2]. The etiology and risk factors for AF following thoracotomy have not been completely identified. It has a multifactorial etiology including change in hemodynamics of the right heart, violation of chest cavity, operative stress, pain leading to increased sympathetic activity, and irritation of the epicardium following violation of the pericardium and patch repair after extrapleural pneumonectomy. Other risk factors include myocardial infarction, presence of coronary artery disease, and postoperative lung embolism [1].
Out of the 130 patients identified, three were excluded due to a prior history of AF. Patients were considered eligible for the study if they experienced AF within the first three days following surgery, and the remaining patients served as controls. Inclusion criteria:
Exclusion criteria:
All patients following extrapleural pneumonectomy and pleurectomy are monitored on surgical intensive care unit (SICU) and step down units with cardiac telemetry at Brigham and Women's Hospital on the Thoracic Floors. Once the arrhythmias were noticed on the monitor, they were documented with a 12 lead ECG. Atrial fibrillation was defined as irregularly irregular heart rate. With 55% of our population sample having received EPP, we could detect an odds ratio of 5.5 with a power of 81% at a significance level of 0.05 (NCSS/PASS). An additional post hoc model with fewer patients was created in order to evaluate the role of structural and functional abnormalities of the heart in AF. Collinearity was assessed by tolerance and variance inflation factors, and the fit of the models was evaluated using Hosmer and Lemeshow goodness-of-fit tests. Calculations were preformed using SAS version 9.1.
Seventy-three patients underwent EPP, and 57 patients had pleurectomy and decortication. Three patients from the EPP group were excluded due to a prior history of AF. A total of 45 patients experienced AF within the first three days of surgery. Thirty-six of these cases occurred in the EPP group, and nine occurred in the pleurectomy group (Table 1). Univariate analyses were conducted in order to compare differences between the two treatment groups for postoperative AF and previously identified risk factors including: age, gender, affected lung, preoperative heart rate, history of coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), and previous beta-blocker therapy (Table 1). Different histological types are associated with better or worse prognosis. Only postoperative AF (P<0.0001) and cell type (P=0.03) were significantly different between the two groups. The EPP group had a significantly larger proportion of patients with postoperative AF and epithelial-type cancer compared to the pleurectomy group. The majority of patients with epithelial histology received EPP, which potentially has significantly prolonged survival compared to pleurectomy [3, 4]. Pleurectomy is considered a purely palliative approach. An additional univariate analysis was conducted in order to evaluate correlations between individual risk factors and AF within three days of surgery (Table 2). COPD was not included in further analyses due to the small sample size, and cell-type was also withheld since the histology of mesothelioma is not a direct risk factor for AF. Preoperative heart rate and age were dichotomized since the small sample size of our study would not permit an accurate analysis of these risk factors as continuous variables. Only EPP was found to be significantly correlated with AF in this analysis (5.8, 95% CI: 2.5, 13.9).
In order to further evaluate the presence of confounders, a full logistic model was created with all the risk factor variables (Table 3). In this model, the odds ratio (OR) for EPP increases to 7.2 (2.8, 18.5) and the OR for age 2.8 (1.1, 7.2) becomes significant (P=0.03). The reduced model (Table 4) demonstrates that the change in the OR for EPP can be explained by placing only age in the model. None of the other risk factors were shown to improve the model based on the use of maximum likelihood ratios (data not shown), and the fit model was determined to be satisfactory based on the non-significant Homser–Lemeshow goodness-of-fit test. Therefore, age is an additional risk factor for AF in our analysis, and patients who are older than 65 years have 2.9 (1.2, 6.8) times the odds of experiencing AF as compared to patients who are 65-year-old and younger.
A subgroup of 56 patients, who received postoperative echocardiogram, 16 of 38 EPP and 3 of 18 pleurectomy patients had at least one structural or functional abnormality (diagnosed in echocardiogram) that predisposed the patient to AF (Table 5). Twenty-one of the 38 EPP patients and six of the 18 pleurectomy patients experienced AF. In a univariate analysis the presence of an abnormality was significantly correlated with the occurrence of AF (OR: 2.9, CI 95%: 0.9, 9.6). In addition, we adjusted the correlation between EPP and AF for the presence/absence of a structural abnormality in a logistic model with 56 patients, who had echocardiogram. When only EPP and age were added to the model, the OR for EPP was 7.982 (1.546, 41.217). The OR decreased to 6.4 (1.2, 35.3) when the presence/absence of an abnormality was added to the model (Table 6) implying that these abnormalities may prove to be significant confounders in a better powered model. Therefore, EPP is most likely an independent risk factor for postoperative AF. Although the charts under review did not extensively comment on pulmonary pressures, seven patients in our dataset had a record of increased pulmonary arterial pressures (Table 7). Five of these patients experienced postoperative AF. It is likely that increased right-heart stress contributes to, but is not sufficient to cause postoperative AF.
The major limitations in our study were the retrospective nature of the study, lack of randomization, and small sample size. However, our results shed light into new aspects in the etiology of postoperative AF. In addition to preexisting cardiac conditions, another significant factor that may contribute to postoperative AF is pneumonectomy. In our series, EPP significantly correlated with AF (5.8, 95% CI: 2.5, 13.9). The increased pulmonary pressure and right atrial stress after complete removal of one lung causes right heart distention in the early postoperative phase, which could increase the risk of arrhythmias. The atrial stretch and dilatation favors the development of atrial ectopy and AF. The role of the left atrial dilation and myocardial stretch has been well studied; however, there is limited literature about the role of the right heart stress in the development of AF. Xiao et al. [5] evaluated the dilation of the right and left atria in 56 consecutive patients with AF. Right atrial dilatation was found in 34, left atrial dilatation in 36, and bi-atrial dilatation in 31 patients. Other authors reported the role of right heart stress in postoperative atrial fibrillation [6, 7]. Some studies have identified right-sided EPP as a risk factor for AF, in addition to other complications [8, 9]. A patch reconstruction of pericardium after pericardial resection with right-sided EPP to prevent herniation of the heart might cause irritation of the epicardium, contributing to arrhythmias. Pericardial patch reconstruction is necessary after right-sided EPP procedures only [8–10]. We were not able to compare right- and left-sided EPP directly in our model since we are primarily comparing pleurectomy to EPP. However, we conducted a univariate analysis of our data to evaluate the relationship between AF and the affected side in EPP patients alone, and we did not observe a significant correlation (Table 2, OR 0.9, P=0.7). Structural heart disease including CAD and valve dysfunction increases the risk of postoperative dysrhythmias [1]. In patients with postoperative AF following EPP (n=16), the echocardiogram demonstrated right ventricular dilation in 12 of 16 patients (75%) and one additional patient had AF and right ventricular hypertrophy after EPP; considering the hypertrophy of right ventricle in this patient, we assume that the patient had longstanding pulmonary hypertension. Structural abnormality of the heart significantly correlated with the occurrence of AF (OR: 2.9, CI 95%; 0.9, 9.6). In addition, we adjusted the correlation between EPP and AF for the presence/absence of a structural abnormality in a logistic model with 56 patients. Using EPP and age in the model showed an OR of 7.982 (1.546, 41.217), which decreased to 6.4 (1.2, 35.3) when the structural abnormalities were added to the model. When the presence/absence of an abnormality alone was used in the model, the OR was 2.3 (P=0.2, Table 6) implying that these abnormalities may be significant confounders. However, in this current model, the addition of this variable did not improve the model according to maximum likelihood ratios. EPP remains most likely an independent risk factor for postoperative AF (Table 6, OR 6.4, P=0.03) in our series. Age has been reported to be a significant risk factor for postoperative AF [11]. Our data demonstrate that patients receiving EPP and who are older than 65 years have greater odds of experiencing postoperative AF as compared to patients receiving EPP and younger than 65 years. The univariate analysis in our series showed that age is not a risk factor (Table 2, OR 1.6, P=0.2); however, a multivariate analysis in a full model (Table 3) demonstrated the age to be a risk factor for postoperative AF (OR 2.8, P=0.03). A multivariate analysis in a Parsimonious model confirmed the role of age as a significant risk factor for AF (Table 4, OR 2.9, P=0.02). From a multivariate analysis in a model that controlled for structural and functional abnormalities and the role of age >65 years, age was found to have a significant impact on postoperative AF (Table 6, OR 13.9, P=0.002). The univariate (Table 2) and multivariate analysis (Table 3) demonstrated that gender, the affected side, preoperative heart rate, presence of coronary artery disease, and preoperative use of beta-blockers were not significant risk factors for postoperative AF in this cohort.
In a series of 856 patients, Passman et al. [11] reported that 17.2% of patients had AF following major, non-cardiac thoracic surgery. The authors reported that male gender, advanced age, and preoperative heart rate
Our study is limited by the smaller sample size and by additional biases that are associated with retrospective studies. We were limited to the information provided in the charts. The EPP group had a significantly larger proportion of epithelial-type cancer as compared to the pleurectomy group.
This cohort highlights the impact of pneumonectomy on hemodynamics change leading to postoperative arrythmias, most likely secondary to right heart stress. Our data demonstrated a significant increase of arrhythmias after extrapleural pneumonectomy compared to pleurectomy. We recommend that any prophylactic measure should address the right heart stress as a significant risk factor for postoperative atrial fibrillation.
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Abstract
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