Abstract
Introduction
The rationale underlying the benefits of the parenchyma-preserving nature of sublobar resection (SR) compared with lobectomy remains unclear. This study aimed to assess postoperative changes in cardiopulmonary function after lobectomy and SR using exercise stress testing.
Methods
This prospective, observational study enrolled patients scheduled for lobectomy or SR. Changes in cardiopulmonary function at 6 months postoperatively were evaluated using exercise stress echocardiography and cardiopulmonary exercise tests.
Results
Initially, 41 patients were enrolled, with 20 patients in the lobectomy group and 18 patients in the SR group (16 segmentectomies, two wedge resections) after excluding three ineligible patients. Preoperatively, all patients demonstrated well-preserved cardiopulmonary function. The systolic pulmonary artery pressure (SPAP) change at peak exercise was significantly higher for lobectomy (median 26.5%; interquartile range [IQR] 0.6–60.1) than for SR (median −8.2%; IQR −38.7–11.7; p = 0.001), despite nonsignificant differences at rest (p = 0.599). Postoperative exercise-induced pulmonary hypertension (exPH) occurred in nine patients (45%) in the lobectomy group but none in the SR group (0%, p = 0.010). Postoperative peak oxygen consumption during exercise decreased significantly in the lobectomy group (median −14.3%; IQR −24.0 to −4.2) compared with that in the SR group (median −7.8%; IQR −13.5–8.7; p = 0.024). The postoperative increase in SPAP at peak exercise (r = 0.402, p = 0.012), prevalence of postoperative exPH (r = 0.978, p = 0.004), and postoperative decrease in peak oxygen consumption (r = −0.330; p = 0.041) were correlated with the number of resected segments.
Conclusions
Lobectomy induces increased SPAP during exercise, exPH, and effort intolerance, compared with SR. This highlights the importance of preserving lung parenchyma in lung surgery.
Clinical Trial Registration
This trial is registered in the UMIN Clinical Trials Registry under the code UMIN000053694.
Keywords: Cardiopulmonary exercise test, Exercise stress echocardiography, Lobectomy, Pulmonary hypertension, Sublobar resection
Introduction
Lobectomy has traditionally been the standard surgical procedure for small-sized NSCLC, as established in a randomized controlled phase III trial from the Lung Cancer Study Group in 1995.1 However, recent pivotal prospective clinical trials have reported the efficacy of sublobar resection (SR) in patients with early-stage NSCLC.2, 3, 4 This has changed the standard of care in lung cancer surgery. Notably, the Japanese Clinical Oncology Group 0802/West Japan Oncology Group 4607 L (JCOG0802/WJOG4607L) reported the superiority of anatomical segmentectomy over lobectomy based on overall survival (OS).2 Fewer patients in the segmentectomy arm died due to cancer of other organs or nonmalignant diseases. Thus, the parenchyma-preserving nature of segmentectomy would lead to a better OS. Nevertheless, in this trial, apparent postoperative respiratory function was not an adequate indicator to assess the clinical benefits of segmentectomy; thus, the physiological basis for the superiority of segmentectomy over lobectomy remains unclear.
Pulmonary resection affects pulmonary hemodynamic and cardiac function, with high rates of cardiorespiratory complications, disabling dyspnea, and decreased functional capacity.5, 6, 7, 8 Particularly, pulmonary resection is hypothesized to increase the afterload by reducing the pulmonary vascular bed, potentially leading to pulmonary hypertension (PH) and right ventricular dysfunction.6, 7, 8, 9, 10, 11, 12, 13 Furthermore, these effects are apparent during exercise.7,8
We hypothesized that postoperative cardiopulmonary function, especially during exercise stress, would vary with the extent of pulmonary resection, such as lobectomy and SR. Understanding this variation may help validate the physiological advantages of preserving the lung parenchyma in lung surgery. Therefore, this study aimed to compare the postoperative changes in cardiopulmonary function after lobectomy and SR using exercise stress tests.
Study Design and Methods
Ethical Statement
This study was conducted in accordance with the principles of the amended Declaration of Helsinki and approved by the Institutional Review Board of Hiroshima University Hospital (approval date: March 23, 2022; approval code: E-2811). Written informed consent was obtained from each participant. This trial is registered in the UMIN Clinical Trials Registry under the code UMIN000053694.
Patient Population
This single-center, prospective, observational study included patients aged 20 to 85 years with an Eastern Cooperative Oncology Group performance score of 0 or 1 who were scheduled to undergo lobectomy and anatomical segmentectomy for clinically suspected primary NSCLC. Eligible patients had no cardiovascular disease, history of ipsilateral thoracotomy, or history of chemotherapy or radiotherapy for any malignant disease within 5 years (prior hormonal therapy was allowed). They also had sufficient organ function. Patients were preoperatively excluded from the primary registration if they met any of the following criteria: (1) active bacterial or fungal infection, (2) pregnancy or breastfeeding, (3) psychosis, (4) uncontrollable diabetes mellitus, or (5) uncontrollable hypertension. In this study, all patients in the SR group were physiologically fit for lobectomy.
The enrolled patients also had trivial or mild tricuspid regurgitation (TR), allowing us to perform a noninvasive evaluation of pulmonary artery pressure (PAP) using Doppler echocardiography. Cardiopulmonary function was evaluated using exercise stress echocardiography (ESE) and cardiopulmonary exercise test (CPET) within 1 month preoperatively (baseline) and 6 months postoperatively. Similarly, plasma biomarkers of myocardial dysfunction were assessed both preoperatively and 6 months postoperatively. The sample size was calculated to detect a 10.0 mm Hg difference in exercise systolic PAP (SPAP) (SD = 10.0, one-sided α = 0.05, 80% power), requiring 25 patients. The enrollment target was set to 30 to account for a 20% dropout rate. The final cohort was expanded to 38 patients to ensure balance in the number of resected segments between groups.
Surgical Procedure
Hybrid video- or robot-assisted thoracic surgery was performed in all patients. Hybrid video-assisted thoracic surgery is a surgical approach that uses both direct vision and television monitor visualization through a 4- to 8-cm thoracotomy. Procedure selection (lobectomy or SR) was based on tumor characteristics; SR was indicated for cases considered technically suitable based on factors including tumor location and size. In cases where no preoperative diagnosis was confirmed, intraoperative frozen section diagnosis was performed after wedge resection. If no malignancies were observed, completing the surgery with wedge resection was permitted. All operative and perioperative management was performed by five board-certified surgeons (A.K., Y.T., Y.M., T.M., N.T., and M.O.). The number of resected segments was counted in each surgical procedure. In wedge resection, the number of resected segments was counted as one segment. The number of resected segments was counted as three segments in right upper lobectomy, two segments in right middle lobectomy, four segments in left lower lobectomy, and five segments each in right lower lobectomy and left upper lobectomy.
Cardiopulmonary Exercise Test and Echocardiographic Assessment
The combined ESE-CPET protocol is found in the Supplementary Material. ESE-CPET data were not available preoperatively to the surgical team. Exercise-induced PH (exPH) was defined as a SPAP of more than 60 mm Hg at peak exercise and the absence of PH at rest.14,15
Statistical Analysis
Patient characteristics were reported as proportions, medians, and interquartile ranges (IQRs). Postoperative changes in cardiopulmonary function were compared between the lobectomy and SR groups. The postoperative rate of change for each cardiopulmonary function indicator was calculated using the following formula: 100 × (postoperative value − baseline value) / baseline value (%). Fisher’s exact test and Wilcoxon ranked sum test were used to compare the lobectomy and SR groups. To evaluate the correlation between pulmonary resection volume (number of resected segments) and changes in pulmonary hemodynamic, the association between continuous variables was assessed using the Pearson or Spearman’s rank correlation coefficients.
Statistical analysis was performed using JMP version 16 (SAS Institute, Cary, NC); statistical significance was set at p less than 0.05. All figures were generated using Prism 9 software (GraphPad Software, Inc., La Jolla, CA).
Results
Enrolled Patients
A total of 41 patients were initially enrolled as registered cohorts between April 1, 2022, and March 31, 2023. Of these, three patients were excluded because they could not undergo echocardiographic assessment due to poor image quality, arrhythmia during testing, and postoperative cerebral infarction unrelated to surgery (Supplementary Fig. 1). Finally, 38 patients were included in the study. The interval from surgery to the postoperative ESE and CPET was a median of 26 weeks for both the lobectomy and SR groups.
Comparison of Changes in Pulmonary Hemodynamics Between Patients Undergoing Lobectomy and Those Undergoing SR
Patient Characteristics
Table 1 summarizes the characteristics of patients in the lobectomy (n = 20) and SR (n = 18) groups. None of the patients had cardiovascular disease. There were more males (p = 0.014) and smokers (p = 0.059) in the lobectomy group than in the SR group. Supplementary Table 1 presents the details of the resected segments in the SR group. The median number of resected segments was four (IQR: 3–4) for the lobectomy group and 1.75 (IQR: 1–2) for the SR group (p < 0.001). The preoperative echocardiographic parameters and exercise-induced hemodynamic responses of the groups, except for tricuspid annular plane systolic excursion (TAPSE) at rest, did not significantly differ (Supplementary Table 2).
Table 1.
Patient Characteristics
| Variablesa | Lobectomy Group |
Sublobar Resection Group |
p Value |
|---|---|---|---|
| (n = 20) | (n = 18) | ||
| Age, y | 71 [65–77] | 70 [60–74] | 0.319 |
| Sex | |||
| Male | 11 (55.0) | 3 (16.7) | 0.014 |
| BMI, kg/m2 | 22.5 [20.8–25.1] | 21.9 [18.9–24.4] | 0.511 |
| Smoking history | |||
| Ever | 12 (60.0) | 5 (27.8) | 0.059 |
| Comorbidity | |||
| Diabetes mellitus | 2 (10.0) | 0 (0) | 0.488 |
| Hypertension | 8 (40.0) | 4 (22.2) | 0.307 |
| Cardiovascular disease | 0 (0) | 0 (0) | 1.0 |
| Respiratory function | |||
| FEV1, mL | 2045 [1845–2750] | 2180 [1755–2455] | 0.983 |
| FVC, mL | 3180 [2500–3910] | 2995 [2298–3428] | 0.966 |
| Tumor location | |||
| RUL/RML/RLL | 8/2/3 (40.0/10.0/15.0) | 5/0/3 (27.8/16.7) | 0.086 |
| LUL/LLL | 4/3 (20.0/15.0) | 10/0 (55.6/0) | |
| Approach | 0.468 | ||
| RATS/hVATS | 4/16 (20.0/80.0) | 6/12 (33.3/66.7) | |
| Number of resected segments | 4 [3–4] | 1.75 [1–2] | <0.001 |
| Surgical time, min | 152 [102–201] | 128 [107–149] | 0.225 |
| Bleeding, mL | 45 [15–147] | 33 [13–57] | 0.306 |
| Postoperative complication, CD grade > II | 0.600 | ||
| Liver dysfunction | 0 (0) | 1 (5.5) | |
| Arrhythmia | 2 (10.0) | 0 (0) | |
| Air leak | 2 (10.0) | 0 (0) | |
| Histology | 0.328 | ||
| Primary lung cancer | 19 (95.0) | 15 (83.3) | |
| Benign | 1 (5.0) | 3 (16.7) |
Note: 11 (55%) in the lobectomy group and 13 (72%) in the SR group had stage I lung cancer. Seven (35%) in the lobectomy group and two (11%) in the SR group had stage II lung cancer.
BMI, body mass index; CD, Clavien–Dindo classification; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; hVATS, hybrid video-assisted thoracic surgery; LLL, left lower lobe; LUL, left upper lobe; RATS, robot-assisted thoracic surgery; RLL, right lower lobe; RUL, right upper lobe.
Categorical data are revealed as number (%) and continuous data as median (interquartile range).
Changes in Pulmonary Function and Blood Biomarkers of Myocardial Function
The forced expiratory volume in 1 second (FEV1) (p = 0.152) and forced vital capacity (FVC) (p = 0.079) revealed a tendency to decrease more in the lobectomy group than in the SR group at 6 months postoperatively (Supplementary Table 3). The coefficients of variation for high-sensitivity troponin T, human atrial natriuretic peptide, N-terminal prohormone of brain natriuretic peptide, creatine kinase-MB, and fibrosis-4 did not differ significantly between the lobectomy and SR groups (Table 2).
Table 2.
Postoperative Change Rate in Cardiopulmonary Function
| Variablesa | Lobectomy Group |
Sublobar Resection Group |
p Value | |
|---|---|---|---|---|
| (n = 20) | (n = 18) | |||
| Plasma biomarkers of myocardial dysfunction | ||||
| hsTnT, % | 29.2 [−2.6–59.4] | 23.6 [0–35.7] | 0.671 | |
| HANP, % | 17.4 [−12.6–77.5] | −1.0 [−31.9–50.6] | 0.381 | |
| NT-pro BNP, % | −20.7 [−34.4–50.2] | −23.0 [−45.3–4.7] | 0.373 | |
| BNP, % | 15.1 [−36.1–52.1] | −26.6 [−45.1–42.0] | 0.169 | |
| FIB-4 index, % | 1.5 [−4.1–23.6] | 8.8 [−11.9–17.7] | 1.0 | |
| CK-MB, % | 0 [−11.1–31.3] | −5.6 [−25.9–9.3] | 0.182 | |
| Exercise stress echocardiography | ||||
| EF, % | 1.5 [0–3.3] | 0 [−3.0–7.3] | 0.837 | |
| E/e', % | Rest | –1.0 [−17.8–22.7] | 1.8 [−8.2–21.8] | 0.793 |
| Peak | −0.9 [−35.5–39.6] | −1.2 [−23.0–49.9] | 0.660 | |
| TRV, % | Rest | −8.3 [−35.0–13.3] | 0 [−21.5–18.1] | 0.516 |
| Peak | 6.6 [1.1–21.7] | −3.7 [−24.7–11.0] | 0.024 | |
| TRPG, % | Rest | −15.9 [−57.7–28.4] | 0 [−38.4–40.1] | 0.516 |
| Peak | 13.6 [2.3–48.0] | −7.3 [−43.3–23.3] | 0.024 | |
| TAPSE, % | Rest | −11.0 [−19.6–4.3] | −10.8 [−26.1–0.1] | 0.661 |
| Peak | −6.0 [−19.0–2.3] | −7.823 [−13.5–8.7] | 0.619 | |
| TVS', % | Rest | 0.9 [−20.9–9.6] | −17.6 [−21.3 to −2.1] | 0.063 |
| Peak | −10.9 [−27.3–13.8] | −7.56 [−20.5–18.5] | 0.413 | |
| RAP, % | Rest | 0 (−62.5–0) | 0 (0–0) | 0.154 |
| Peak | 0 [−35.0–146.9] | 0 (−11.7–0) | 0.539 | |
| SPAP, % | Rest | −7.4 [−51.4–12.9] | 0 [−23.0–40.0] | 0.599 |
| Peak | 26.5 [0.5–60.1] | −8.2 [−38.7–11.7] | 0.010 | |
| Cardiopulmonary exercise test | ||||
| Peak VO2, % | −14.3 [−24.0 to −4.2] | −7.8 [−13.5–8.7] | 0.024 | |
| Peak VO2/HR, % | −9.6 [−16.0 to −4.0] | −5.22 [−9.2–1.7] | 0.093 | |
Note: E/e,' ratio of early transmitral velocity (E) to mitral annular early diastolic velocity (e').
BNP, brain natriuretic peptide; CK-MB, creatine kinase-MB; EF, ejection fraction; FIB-4 index, fibrosis-4 index; RAP, right atrial pressure; HANP, human atrial natriuretic peptide; HR, heart rate; hsTnT, high-sensitivity troponin T; NT-pro BNP, N-terminal prohormone of brain natriuretic peptide; SPAP, systolic pulmonary artery pressure; TAPSE, tricuspid annular plane systolic excursion; TRPG, tricuspid regurgitant pressure gradient; TRV, tricuspid regurgitation velocity; TVS’, tricuspid annulus velocity; VO2, oxygen consumption.
Continuous data are illustrated as median (interquartile range).
Changes in Pulmonary Hemodynamics as Evaluated by ESE
The peak exercise respiratory exchange ratios of the lobectomy and SR groups before (p = 0.482) or after the surgery (p = 0.862) did not differ significantly (Supplementary Fig. 2). The postoperative rate of change in SPAP at rest did not differ significantly across groups (median change rate: −7.4% [IQR: −51.4 to −12.9] in the lobectomy group, 0% [IQR: −23.0–40.0] in the SR group; p = 0.599; Fig. 1A). SPAP at peak exercise was significantly higher in the lobectomy group (median change rate: 26.5%; IQR: 0.6–60.1) than in the SR group (median change rate: −8.2%; IQR: −38.7 to −11.7; p = 0.010; Fig. 1B) at 6 months postoperatively. When categorizing the rate of increase in SPAP into three groups (≤20%, >20% and ≤40%, >40%), there was no significant difference in SPAP at rest between the lobectomy and SR groups (p = 0.525; Fig. 1C). However, a significantly higher rate of increase in SPAP was observed in the lobectomy group than in the SR group (p = 0.024; Fig. 1D) at peak exercise. There was no significant correlation between the change in either FVC or FEV1 and the change in SPAP at peak exercise (r = −0.088, p = 0.598 and r = −0.118, p = 0.480, respectively).
Figure 1.
(A, B) Comparison of SPAP (A) at rest and (B) during peak exercise between the lobectomy and sublobar resection groups. The error bars represent interquartile ranges. (C, D) The rates of increase in the SPAP are categorized into three groups (blue: ≤20%; green: >20% and ≤40%; red: >40%) and compared between the lobectomy and sublobar resection groups (C) at rest and (D) during peak exercise.
Regarding the echocardiographic parameters, the postoperative change rates of TR velocity (p = 0.024) and tricuspid regurgitant pressure gradient (p = 0.024) were significantly higher in the lobectomy group than in the SR group (Table 2). Postoperatively, the mean PAP (MPAP)/cardiac output (CO) slope was significantly higher in the lobectomy group than in the SR group (p = 0.009), despite the nonsignificant differences preoperatively (p = 0.682; Supplementary Fig. 3). The change rates of other parameters, including E/e’, TAPSE, tricuspid annulus velocity, and right atrial pressure, were not significantly different between the lobectomy and SR groups (Table 2). Comparison of changes in pulmonary hemodynamics in only patients with stage I NSCLC is found in Supplementary Figure 4.
Exercise-Induced PH
No patients in either group had PH at rest. Preoperatively, exPH was observed in one patient in each group (Fig. 2A). At 6 months postoperatively, exPH was observed in nine patients (45%) in the lobectomy group but none in the SR group (0%, p = 0.001; Fig. 2A). Regarding sex, the prevalence of postoperative exPH was higher after lobectomy than after SR in both males (54.6% versus 0%; Fig. 2B) and females (33.3% versus 0%; Fig. 2C). Similarly, regarding age (<70/≥70 y old) and smoking history (ever/never), the prevalence of postoperative exPH was higher after lobectomy than after SR in all subgroups (Supplementary Fig. 5).
Figure 2.
(A) Comparison of pre- and postoperative exercise-induced pulmonary hypertension prevalence (%) between the lobectomy and sublobar resection groups. (B, C) Comparison of pre- and postoperative exercise-induced pulmonary hypertension prevalence (%) in (B) male and (C) female patients between the lobectomy and sublobar resection groups.
Changes in Cardiopulmonary Function Evaluated by CPET
The postoperative peak oxygen consumption (VO2) and peak VO2/heart rate (HR) were lower in the lobectomy group (median change rate of peak: VO2, −14.3%; IQR: −24.0 to −4.2; median change rate of peak: VO2/HR, −9.6%; IQR: −16.0 to −4.0) than in the SR group (median change rate of peak: VO2, −7.8%; IQR: −13.5–8.7; median change rate of peak: VO2/HR, −5.2%; IQR: −9.2–1.7; p = 0.024 and p = 0.093, respectively) (Fig. 3A, B). There was no significant correlation between the change in either FVC or FEV1 and the change in peak VO2 (r = 0.336, p = 0.039 and r = 0.230, p = 0.165, respectively).
Figure 3.
Comparison of postoperative change rates in (A) peak VO2 and (B) peak VO2/HR between the lobectomy and sublobar resection groups. Error bars represent the interquartile range. HR, heart rate; op, operation; VO2, oxygen consumption.
Correlation Between Changes in Pulmonary Hemodynamics and Pulmonary Resection Volume
No correlation was observed between the postoperative change rate of SPAP at rest and the number of resected segments (r = 0.126, p = 0.450; Fig. 4A). However, the postoperative change rate of SPAP at peak exercise (r = 0.402, p = 0.012; Fig. 4B) and prevalence of postoperative exPH (r = 0.978, p = 0.004; Fig. 4C) were positively correlated with the number of resected segments. In addition, the postoperative peak VO2 negatively correlated with the number of resected segments (r = −0.330; p = 0.041; Fig. 4D).
Figure 4.
(A, B) Postoperative change rate (%) of SPAP (A) at rest and (B) during peak exercise stratified by the number of resected segments. Error bars represent the interquartile range. (C) Postoperative exercise-induced pulmonary hypertension prevalence (%), stratified by the number of resected segments. (D) Postoperative change rates of the peak VO2, stratified by the number of resected segments. Error bars represent the interquartile range. IQR, interquartile range; SPAP, systolic pulmonary artery pressure; VO2, oxygen consumption.
Discussion
This is the first study to demonstrate differences in postoperative exercise-induced hemodynamic responses according to the extent of pulmonary resection, providing a novel perspective on the differences in postoperative changes in cardiopulmonary function based on surgical procedure. Remarkably, a positive correlation was identified between the number of resected segments and exercise-induced cardiopulmonary dysfunction, underscoring the importance of preserving the lung parenchyma to the greatest extent possible. In addition, patients who underwent lobectomy developed exPH and effort intolerance at high frequencies, although SR preserved postoperative cardiopulmonary function.
Cardiopulmonary dysfunction after pulmonary resection has recently received increasing attention.10,11 A decrease in the pulmonary vascular bed due to major lung resection increases pulmonary vascular resistance and plays a pivotal role in the development of postoperative PH and right ventricular dysfunction.6, 7, 8,11, 12, 13 However, several studies indicated that increased HR, pulmonary arterial pressure, central venous pressure, and pulmonary vascular resistance index were observed only during exercise after major lung resection.7,8 This means that changes in right ventricular function at rest compensate for the increased right ventricular volume, but adequate compensation does not occur under conditions of increased pulmonary blood flow during exercise. Specifically, in the lobectomy group, PAP did not change at rest but markedly increased during exercise.
Similar to the implications in healthy individuals during increased CO (e.g., during exercise), pulmonary vascular flow reserve reflects the ability of the pulmonary circulation to accommodate increased CO without excessive increases in PAP.10 However, with increased pulmonary blood flow during exercise, lobectomy is thought to induce a decrease in the ability of the pulmonary circulation system, leading to an inability to adapt to the acute increase in the afterload during exercise. Conversely, PAP was not elevated after SR, even during exercise; SR fully preserved hemodynamic adaptation to these conditions, with the ability of the pulmonary circulation to preserve the pulmonary vascular bed. Notably, the MPAP/CO slope, which correlates with an abnormal pulmonary vascular reserve,16 did not vary pre- or postoperatively in the SR group.
Furthermore, 45% of patients in the lobectomy group developed exPH after surgery, compared with none in the SR group. In recent years, the clinical significance of exPH as a potential cause of cardiac dysfunction has gained acceptance in recent years.14,15,17, 18, 19, 20 Previous reports hypothesized that exPH is an intermediate pathophysiological stage between normal hemodynamics and pulmonary vasculopathy, with PH at rest.19,21,22 It is independently associated with a higher risk of decreased exercise capacity, decreased life expectancy, exertional dyspnea, and poor prognosis.14,19,20 In this study, PH at rest and right ventricular dysfunction were not clearly observed, even after lobectomy. However, exPH may precede the development of future PH and right ventricular dysfunction.23 In addition to exPH, effort intolerance—objectively measured by reduced peak VO2 using the CPET—was more significant after lobectomy than after SR. These results indicate that lobectomy potentially induces cardiopulmonary dysfunction and, relative to SR, decreases the ability to perform physical exercise and tolerability during physical exertion.
The difference in cardiopulmonary dysfunction may reflect variations in the mortality risks of patients after lobectomy and SR. In the JCOG0802/WJOG4607L trial, segmentectomy was considered to be more advantageous than lobectomy because it allowed for extensive treatment of subsequent diseases after primary lung resection, such as recurrence and second primary cancer.2 Despite considerable evidence, the clinical superiority of segmentectomy remains ambiguous when assessed using static metrics, such as respiratory function. Our findings suggest that the true benefit of parenchyma-preserving surgery may not be fully captured by static pulmonary function tests at rest. Instead, the preservation of the pulmonary vascular bed, which maintains cardiopulmonary reserve during exercise and prevents the development of exPH, may be a critical factor contributing to better long-term outcomes and tolerance to subsequent life events or illnesses. The dynamic assessment of cardiopulmonary function, as performed in our study, reveals a definite advantage of SR that static metrics fail to reveal. These insights contribute significantly to the understanding of the JCOG0802/WJOG4607L findings.2 Furthermore, the results provide an important rationale for promoting the expansion of surgical indications for SR in the context of a new era of lung cancer surgery after the JCOG/WJOG and CALGB trials.24
This study used a noninvasive exercise stress test to assess cardiopulmonary function. ESE-CPET is a well-known, noninvasive, and clinically useful method for assessing hemodynamic responses during exercise.25 In addition, exercise stress testing of pulmonary circulation for the diagnosis of latent or early-stage PH is gaining acceptance. A previous study reported an agreement between echocardiographic and invasive measures (catheterization) of PAP and CO during exercise.16,25 Thus, it is possible to noninvasively and accurately assess cardiopulmonary function during exercise using ESE-CPET.
This study has several limitations. First, this was a prospective study without randomization, and the introduced systematic bias could not be overcome using inferential statistics. Second, this was a single-center study, and the sample size was small, in spite of a pre-study power calculation. The small sample size may limit the generalizability of our findings. Therefore, our results should be considered exploratory, and larger, multicenter prospective studies are needed to confirm these findings. Third, patients with undetectable TR at rest were excluded because of potential confounding effects on PAP.16 Therefore, our findings cannot be extrapolated to patients without TR. Fourth, the exclusion of three patients who were unable to complete testing may have led to a potential selection bias. Finally, the clinical significance of exPH after lung resection remains unclear, although it negatively affects patients with cardiovascular disease or chronic obstructive pulmonary disease.14,15,26 There was a lack of information regarding quality-of-life symptoms or daily activity limitations. Therefore, further research is required to elucidate the clinical relevance and outcomes in patients with exPH and effort intolerance after lung resection.
In conclusion, SR, which includes anatomical segmentectomy and wedge resection, effectively preserves postoperative cardiopulmonary function. However, lobectomy induces postoperative exPH and effort intolerance during exercise stress. This implies that SR has a lesser physiological impact than lobectomy and underscores the significance of preserving the lung parenchyma using SR.
CRediT Authorship Contribution Statement
Atsushi Kamigaichi: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing - original draft.
Yasuhiro Tsutani: Data curation, Methodology, Writing - review & editing.
Akane Tsuchiya: Data curation, Investigation, Methodology, Supervision.
Hiroto Utsunomiya: Data curation, Investigation, Methodology, Writing - review & editing.
Yoshihiro Miyata: Data curation, Writing - review & editing, Supervision.
Takahiro Mimae: Data curation, Supervision.
Norifumi Tsubokawa: Data curation, Supervision.
Yukiko Nakano: Data curation, Supervision.
Morihito Okada: Data curation, Supervision.
Disclosure
The authors declare no conflict of interest.
Acknowledgments
The authors thank all patients for participating in this study. IRB approval E-2811 (approval date: March 23, 2022). Written informed consent was obtained from each participant.
Funding
No funding support was received.
Footnotes
Previous presentation: The 33rd European Conference on General Thoracic Surgery of the European Society of Thoracic Surgeons in Budapest, Hungary on May 25 to 27, 2025.
Cite this article as: Kamigaichi A, Tsutani Y, Tsuchiya A, et al. Lobectomy induces exercise-induced pulmonary hypertension and effort intolerance compared with sublobar resection. JTO Clin Res Rep 2025;6:100903
Note: To access the supplementary material accompanying this article, visit the online version of the JTO Clinical and Research Reports at www.jtocrr.org and at https://doi.org/10.1016/j.jtocrr.2025.100903.
Supplementary Data
Supplementary Figure 1.
Supplementary Figure 2.
Supplementary Figure 3.
Supplementary Figure 4.
Supplementary Figure 5.
References
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