Long-term survival of patients undergoing off-pump coronary artery bypass grafting combined with pulmonary lobectomy

Introduction

Worldwide, coronary artery disease (CAD) and lung cancer are among the principal causes of death and disease, posing substantial challenges to public health systems. In China, CAD ranks as the second leading cause of premature death, while lung cancer is the third, underscoring the significant burden of these conditions within the population (1,2). The prevalence of both conditions continues to rise, and they share common risk factors such as smoking, hypertension, and hyperlipidemia, which contribute to the increasing number of patients diagnosed with both conditions concurrently (3).

The treatment of patients with coexisting CAD and lung cancer presents a complex clinical challenge. Traditional approaches involve either staged or simultaneous surgeries, each associated with distinct advantages and risks. Staged surgeries, where CAD is treated first followed by lung cancer resection or vice versa, can lead to prolonged hospital stays, increased exposure to anesthesia, and higher cumulative risks of complications. Moreover, the delay between surgeries could allow for tumor progression or exacerbate the risk of cardiovascular events.

In recent years, the feasibility of performing off-pump coronary artery bypass grafting (OPCABG) concurrently with lung cancer resection has been investigated as a strategy to mitigate the risks associated with staged procedures. OPCABG reduces the physiological stress associated with cardiopulmonary bypass, which is particularly beneficial for patients with compromised cardiac function or those at high risk for complications related to extracorporeal circulation. Furthermore, performing both procedures in a single session can reduce the overall burden on the patient, both physically and financially, by minimizing the need for multiple hospitalizations and recovery periods (4).

However, the safety and efficacy of this combined surgical approach remain subjects of ongoing debate. Concerns have been raised regarding the increased surgical complexity, the impact on postoperative recovery, and the long-term outcomes in terms of survival and quality of life. The interaction between the two diseases and the effects of surgical stress on tumor biology remain areas of active investigation. For example, the inflammatory response and potential immunosuppression induced by surgery could theoretically affect tumor progression and response to treatment.

Despite these concerns, preliminary studies have yielded promising results, indicating that combined OPCABG and lung cancer resection may be a viable option for selected patients (3). The criteria for patient selection are critical and typically involve a comprehensive assessment of cardiac function, tumor characteristics, and overall patient health. The aim of our study is to expand the current body of knowledge by examining the long-term clinical outcomes of patients who underwent concurrent OPCABG and pulmonary lobectomy, and to identify prognostic factors that may assist in treatment planning and decision making. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-695/rc).

Methods

Patients selection

This retrospective study included 57 consecutive patients with lung cancer and CAD who underwent concurrent OPCABG and pulmonary lobectomy at Beijing Anzhen Hospital between May 2006 and December 2019. All patients were clinically diagnosed with pulmonary malignancy and CAD through preoperative diagnostic techniques, including angiography, computerized tomography (CT), and magnetic resonance imaging (MRI), and they met the surgical indications for both procedures. Concurrent combined surgery is a difficult and low-frequency operation in the clinic. The study spans 13 years [2006–2019] and covers all eligible consecutive cases from Anzhen Hospital in Beijing, reflecting real-world accessible samples. Exclusion criteria included patients with pulmonary benign tumors (e.g., hamartoma, granuloma, adenomatous hyperplasia, or tuberculosis), other malignancies, concurrently received radiofrequency ablation or preoperative neoadjuvant (chemotherapy/immunotherapy), or those who declined participation. And excluded people who lost contact during follow-up. The surgical protocol, such as incision type and vascular graft type, was jointly designated by the cardiovascular surgery and thoracic surgery teams. The thoracic surgery department ruled out benign or other malignant tumors by imaging and pathological reports. Pathologists will make a pathological diagnosis based on the actual pathological condition of the specimen and in combination with the location of the specimen within the human body. All clinical procedures were performed in accordance with current clinical guidelines and regulations.

The combined surgical procedure

Coronary artery revascularization was performed via a median sternotomy, utilizing an Octopus system for cardiac stabilization. In the majority of procedures, the left anterior descending (LAD) artery was bypassed with the left internal thoracic artery (LITA), while saphenous vein grafts were employed to revascularize other target vessels. Subsequent pulmonary lobectomies were performed, either with or without thoracoscopic assistance. The branches of the pulmonary veins, pulmonary arteries, and bronchi were individually dissected and subsequently ligated or stapled. This was followed by a systematic dissection of the hilar and mediastinal lymph nodes. Upon completion of the procedure, pleural chest tubes and mediastinal drains were placed. It is noteworthy that in the early phase of our experience with this combined procedure, the cardiac and pulmonary operations were conducted through separate sternotomy and thoracotomy incisions. A lateral thoracotomy or muscle-sparing incision was used for standard lung resection and dissection of the lymph nodes. The patient was repositioned from supine to the lateral decubitus position following the cardiac procedure. In more recent cases, two incisions were reserved solely for complicated tumor resections. The majority of lobectomies in this series were conducted via a sternotomy, supplemented by thoracoscopic assistance. The thoracoscope and video-assisted thoracoscopic surgery (VATS) instruments were primarily employed for mediastinal lymphadenectomy, which was performed through two discrete small incisions at the fourth and seventh intercostal spaces near the midaxillary line. A single thoracotomy approach was exclusively applied to patients with single-vessel disease and an ipsilateral lung nodule; for instance, those with LAD artery disease and concomitant left lung cancer, or right coronary artery (RCA) narrowing with a concurrent right lung malignancy.

Data collection

During the initial visit, baseline characteristics such as age, sex, symptoms, medical history, and family history were recorded. Data were collected on overall survival time and the presence or absence of postoperative complications. Postoperative complications included new cardiovascular and cerebrovascular events and tumor metastasis. Data including patient medical records, electrocardiography results, biochemical test results, and pathological diagnosis outcomes were collected through Beijing Anzhen Hospital’s electronic medical record system. Follow-up data is obtained through outpatient reviews or telephone interviews.

Patient follow-up

Patients were scheduled for follow-up visits 30 days, 3 months, and 6 months postoperatively, and then every 6 months until the second postoperative year. Then the follow-up visits were performed every year.

All patients were routinely followed up in the clinic or via telephone. The first follow-up visit included electrocardiogram (ECG) and antero-posterior and lateral chest X-rays. The follow-up visits at 3 and 6 months postoperative included ECG, echocardiography. The follow-up aimed to document any adverse events, including survival status, tumor condition, chemotherapy status, re-hospitalization for heart failure, cardiovascular events. Among them, the long-term mortality rate of the patients is the primary endpoint event.

Statistical analysis

Statistical analysis was performed using R software was used to perform the necessary analysis, including normality test, t-test and Cox regression analysis of the data. Descriptive statistics are presented as frequencies and percentages for categorical variables and as mean ± standard deviation for continuous variables. Between-group comparisons were performed using the Chi-squared or Fisher’s exact test for categorical variables, as appropriate. For continuous variables, the independent samples t-test was applied for normally distributed data, whereas the Mann-Whitney U test was used for non-normally distributed data. Bilateral P<0.05 was considered statistically significant. Furthermore, X-lite was used to determine the optimal cut-off values. SPSS Statistics 25.0 was used to proceed Kaplan-Meiers survival analyses and receiver operating characteristic (ROC) curves, while Graphpad Pism 9.5 were created to make the Kaplan-Meiers survival curve. Subgroup analyses revealed that patients aged >69 years with stage III tumors had the worst prognosis (interaction P=0.01).

Ethical statement

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Ethics Committee of Beijing Anzhen Hospital (No. 2024130X) and informed consent was taken from all the patients.

Results

Baseline characteristic

The baseline characteristics of the study cohort are summarized in Table 1. A total of 57 patients were included, with a mean age of 65.07±6.13 years (range, 53–77 years). The majority of participants were male (87.80%). Nearly half of the patients (45.60%) presented with New York Heart Association (NYHA) functional class III or higher. The mean left ventricular ejection fraction was 59.00%, and the average number of diseased coronary vessels was 2.54±0.88. The distribution of CAD by vessel number was as follows: three-vessel disease was most prevalent (n=27, 47.36%), followed by two-vessel (n=15, 26.32%), one-vessel (n=9, 15.79%), and four-vessel disease (n=6, 10.53%).

Regarding preoperative comorbidities, hypertension was the most common (61.40%), followed by unstable angina (59.64%), diabetes mellitus (31.58%), and a history of either percutaneous coronary intervention (PCI) or myocardial infarction (each 14.04%). With respect to tumor location, the majority of lung tumors were situated in the right upper lobe (n=13, 22.81%), while the right middle lobe was the least common site (n=7, 12.28%). The remaining cases were distributed among other lobes (n=12, 21.05%).

Surgical outcomes

The perioperative characteristics of the patients are summarized in Table 2. There were no intraoperative deaths. One patient died during hospitalization due to postoperative low cardiac output syndrome, and another died from respiratory failure secondary to acute respiratory distress syndrome (ARDS) caused by an acute exacerbation of interstitial lung disease. The in-hospital survival rate was 98.25% (56/57). No other cases of mortality or new-onset myocardial infarction were recorded.

The mean number of coronary anastomoses was 2.52±0.90. Regarding the extent of revascularization, three-vessel coronary artery bypass grafting (CABG) was the most common (n=25, 43.86%), followed by two-vessel (n=16, 28.07%), one-vessel (n=9, 15.79%), and four-vessel bypass (n=7, 12.28%). The great saphenous vein (GSV) was used as the sole conduit in 15 patients (26.32%). A single left internal mammary artery (LIMA) was utilized in 6 patients with significant stenosis of the LAD artery, while a combination of LIMA and GSV grafts was employed in 15 patients. All patients received dual antiplatelet therapy with aspirin and clopidogrel postoperatively. The surgical approach was tailored to each patient’s specific condition. A total of 33 patients underwent both cardiac and pulmonary procedures via a median sternotomy. A hybrid approach was employed in 15 patients, combining median sternotomy for CABG with VATS for lung resection. In another 14 patients, a staged incision strategy was adopted: 7 underwent CABG via median sternotomy followed by lung resection via left thoracotomy, while the other 7 underwent CABG via median sternotomy followed by lung resection via right thoracotomy.

Postoperative complications included surgical site infections in three patients and two patients requiring tracheostomy. Other complications observed in single cases included atelectasis, multiple cerebral infarctions, and impaired wound healing. The mean intraoperative blood loss was 796.59±407.09 mL. The average operative duration was 4.73±0.83 hours. Patients spent an average of 1.76±2.34 days in the intensive care unit, with a mean hospital stay of 35.39±31.87 days. Pathological outcomes are detailed in Table 3. According to the 2021 World Health Organization (WHO) classification of lung tumors (5), stage IA was the most prevalent tumor-node-metastasis (TNM) stage (29.82%), followed by stage IIA (28.07%) and stage IIB (22.81%). Adenocarcinoma was the predominant histological type (61.80%), followed by squamous cell carcinoma (29.00%) and other types (9.00%). All patients achieved complete R0 resection.

Patients follow-up

Follow-up ended in May 2024. The mean follow-up time was 85.39±49.70 months and the mean survival time was 85.39±49.70 months. The 5-year survival rate was 78.95%. During the follow-up period, 21 patients received chemotherapy, 3 patients were treated with targeted drugs, and 14 patients experienced relapse. A total of 12 patients died, including 2 patients who died during hospitalization due to low cardiac output and respiratory failure, respectively, and 6 patients who died over a 5-year period due to tumor progression; 4 patients died of metastatic lung cancer 5 years after surgery. No new myocardial infarction or heart failure readmissions.

Prognostic analysis

In the Cox regression analysis, age [hazard ratio (HR): 1.223, 95% confidence interval (CI): 1.067–1.402, P=0.004] and tumor stage (HR: 5.384, 95% CI: 1.917–15.125, P=0.001) emerged as significant predictors of adverse event risk, indicating a strong association between these factors and unfavorable outcomes. Patients with a tumor stage of 3 or higher (HR: 7.956, 95% CI: 2.520–25.115, P<0.001) had a markedly increased risk, with the area under the curve (AUC) was 0.715. Individuals aged 69 years or older (HR: 3.376, 95% CI: 1.086–10.495, P=0.04) were classified as adverse prognostic factors, achieving an AUC of 0.657. These findings are further illustrated by survival analysis curves (Figures 1,2), which display the time-dependent changes in survival rates across different groups. The Kaplan-Meiers survival curve demonstrates a decline in overall survival rate over time. Subgroup analysis reveals that patients with age <69 years and tumor stage <III exhibit significantly longer survival times. Relevant data from cox regression analysis are presented in Table 4.

Figure 1 Kaplan-Meier survival curves for age groups.

Figure 2 Kaplan-Meier survival curves for stage groups.

Discussion

Lung cancer is currently the most prevalent and deadly malignancy in our country. In parallel, the incidence of coronary heart disease (CHD) is steadily increasing. Both conditions are associated with a higher risk of mortality, particularly among older patients. Additionally, these diseases are interrelated and share common risk factors (6). The timely management of CHD is paramount for minimizing perioperative risk in patients undergoing lung cancer surgery. Nevertheless, the treatment of patients requiring concomitant cardiac surgery and lung resection for cancer continues to pose a significant clinical challenge (4). The increasing adoption of PCI has expanded its application in managing patients with CAD who are candidates for surgery. Paradoxically, evidence indicates that lung cancer patients undergoing preoperative PCI face an elevated risk of subsequent revascularization, both in the immediate perioperative period and in the long term (7). This risk is significantly amplified when the interval between PCI and thoracic surgery is under one year. Moreover, the one-year risks of repeat revascularization and all-cause mortality following PCI are substantially higher in patients with concomitant CAD and lung cancer than in those with CAD alone (8). Consequently, stent placement should generally be deferred in patients anticipated to undergo surgery shortly after coronary intervention. In such scenarios, balloon angioplasty is often the preferred revascularization strategy, despite its recognized limitations in long-term efficacy (9). If the interval between the two procedures is prolonged, the risk of lung cancer metastasis may also increase.

Once lung cancer is diagnosed, surgical resection should be performed as soon as possible. If heart surgery is performed first, lung surgery is typically recommended 3–6 weeks after CABG to ensure adequate anticoagulation. However, this delay may lead to tumor progression. On the other hand, performing lung tumor removal first in the perioperative period can result in serious cardiovascular events, leading to fatal complications (10). The staged surgical approach imposes the cumulative burden of two separate episodes of general anesthesia, distinct thoracic incisions, and a protracted cumulative hospital stay. Furthermore, securing patient acceptance for two major procedures within a short timeframe can be clinically challenging. In contrast, a concurrent management strategy mitigates these drawbacks by obviating the need for a second operation, thereby reducing cumulative perioperative stress and morbidity, and potentially conferring economic advantages through consolidated resource utilization and shorter overall hospitalization (11).

n this series, a one-stage surgical strategy was employed, utilizing an off-pump CABG technique. The analysis revealed that off-pump CABG demonstrated non-inferiority to the conventional on-pump approach, with comparable mid-term mortality and long-term morbidity rates. However, immunosuppressive factors such as interleukin-10, which are present in the blood during cardiopulmonary bypass, may promote tumor growth and metastasis (12). The off-pump CABG technique offers a significant advantage by obviating the need for full systemic heparinization, thereby reducing the risk of bleeding during subsequent tumor resection. In the one-stage procedure, CABG is typically performed first, as it is inherently more aseptic than pulmonary surgery. This sequence also ensures a stable coronary blood supply prior to lung manipulation, which is critical for preventing intraoperative myocardial ischemia and maintaining cardiac function. When deciding to perform simultaneous cardiopulmonary surgery, the choice of surgical incision must be carefully considered. In this study, two surgical approaches were used for 17 patients, who received both a median sternotomy and lateral thoracotomy. A single surgical incision was utilized in 41 patients, with the majority (n=33) undergoing a median sternotomy and the remainder (n=8) a lateral thoracotomy. Specifically, a single left lateral thoracotomy provided access for both CABG and left lower lobectomy or pneumonectomy. In an additional 15 patients, a hybrid approach was employed, combining median sternotomy for CABG with VATS for right-sided lobectomy. At Beijing Anzhen Hospital, the choice between a single incision or a combination of median and lateral incisions depends on the specific conditions of the patient. Generally, tumor size and location are the main factors determining the surgical approach for the one-stage operation. The use of thoracoscopy significantly enhances the anatomic visualization of the mediastinum and lymph nodes during surgery. Previous investigations have consistently established that thoracoscopic lobectomy is associated with superior perioperative outcomes compared to the open approach, notably including a shorter hospitalization duration, reduced postoperative pain, superior preservation of pulmonary function, and a lower incidence of postoperative complications (13).

In this study, there was only one perioperative death in the hospital. In contrast, previously published studies have reported in-hospital mortality rates for the combined surgical procedure ranging from 0% to 5.26% (14). Postoperative recovery posed a significant challenge in a subset of patients. One individual developed a severe lung infection requiring tracheotomy. The incidence of acute renal failure was principally modulated by the combined effects of surgical insult and pre-existing renal compromise. Emerging evidence also suggests that LIMA harvesting for grafting in lung cancer patients may predispose to sternotomy wound complications, including impaired healing and dehiscence, potentially due to compromised collateral blood supply. This patient required debridement due to poor wound healing. Pulmonary embolism, commonly seen in cancer patients, is closely associated with a hypercoagulable state. In this study, all postoperative complications were promptly diagnosed and treated appropriately.

Previous studies have shown that concurrent surgery does not increase surgical trauma or prolong postoperative recovery in patients (4). In the present study, the cumulative 5-year survival rate was 47.9%, which is notably lower than the 64–67% range reported in prior literature (15). This discrepancy may be attributable to differences in patient cohort characteristics, particularly cancer staging. For context, established lung cancer survival statistics demonstrate a pronounced decline with advancing stage, from 60–80% in stage I to 40–60% in stage II and 6.7–20.8% in stage III (16). This work has notable limitations, such as its non-randomized, prospective nature and modest sample size. The establishment of a control group was impractical due to overwhelming patient preference for the one-stage strategy. However, the low complication rate and alignment with existing studies offer compelling evidence for the safety and technical feasibility of the combined surgery. This study analyzes the factors influencing patients’ long-term survival based on previous research. Previous studies have shown that concurrent CABG and lobectomy is safe and effective in elderly patients. However, the aging heart is less tolerant to stimulation, leading to a higher risk of surgery and increased likelihood of postoperative complications (17). Once a cancer diagnosis is confirmed, the more advanced the tumor stage, the poorer the surgical outcome, the higher the recurrence rate, and the greater the mortality risk. Therefore, the decision to proceed with simultaneous OPCABG and lung cancer resection should be carefully evaluated based on the patient’s age and the stage of cancer.

The results of this retrospective clinical study suggest that concurrent CABG and lung cancer resection are effective in patients with both CAD and lung cancer. However, concurrent surgery is not recommended for patients over the age of 69 years (HR: 3.376, 95% CI: 1.086–10.495, P=0.04, AUC =0.657) or for those with tumor stage III or higher (HR: 7.956, 95% CI: 2.520–25.115, P<0.001, AUC =0.715).

Although this study provides preliminary evidence for simultaneous OPCABG with lung cancer resection and suggests that this combination therapy has some efficacy in terms of long-term survival and safety, there are still many aspects that need to be further explored. First of all, considering the small sample size and retrospective design of the study, future multicenter, prospective randomized controlled trials will be able to provide more solid evidence support to verify the universality and reliability of the findings of this study. Secondly, individual differences of patients may have an impact on the choice of surgical protocol and prognosis, so future studies can further explore the potential impact of different types of CAD, lung cancer stage and other comorbidities on surgical efficacy. In addition, with the continuous advancement of technology, different surgical methods (such as the combination of total thoracoscope and open surgery) may have different effects on postoperative recovery, complication rate and long-term survival of patients. Consequently, subsequent investigations should prioritize large-scale, multi-center collaborative research. Key objectives include expanding the patient cohort and conducting comparative effectiveness studies on various surgical techniques, with the objective of generating high-level evidence to inform standardized clinical protocols for this combined modality.

Conclusions

OPCABG combined with pulmonary resection is a safe and effective approach for treating patients with both CAD and lung cancer. Age and tumor stage were significantly associated with postoperative survival, with tumor stage above III demonstrating stronger predictive value for prognosis than age. For patients aged 69 years or older who have stage III or higher tumors, surgical decisions should be carefully evaluated due to the potentially elevated risk of adverse outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-695/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-695/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-695/prf

Funding: This study was supported by a grant from the National Science Foundation of China (No. 82200302 to H.G.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-695/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by Ethics Committee of Beijing Anzhen Hospital (No. 2024130X). Written informed consent was obtained from all participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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