Abstract
Background/Aim: The effect of left ventricular systolic dysfunction (LVSD), a risk factor for postoperative mortality, in older adult patients with gastric cancer has not been fully elucidated. This study aimed to evaluate the impact of low preoperative left ventricular ejection fraction (EF) on short- and long-term outcomes in older adult patients with gastric cancer. Patients and Methods: This retrospective study enrolled 237 older adult patients with gastric cancer (≥75 years old) who underwent preoperative echocardiography and curative gastrectomy. LVSD was defined as an EF <50%. Postoperative complications and prognosis were compared between patients with low- and normal-EF using the Fisher’s exact or Chi-square test, log-rank test, Kaplan–Meier method, and Cox regression analysis. Results: Thirteen patients (5.4%) exhibited LVSD. The incidence of postoperative complications was not significantly different between the two groups (p=0.470), although the incidence of pneumonia was high (p=0.003) and overall survival was significantly worse in the low-EF group compared to the normal-EF group (p=0.016). Multivariate analysis revealed that decreased EF, low preoperative body mass index, and advanced pathological stage were significant prognostic factors in older adult patients with gastric cancer. Conclusion: LVSD increases the risk of postoperative pneumonia and has a negative prognostic impact on older adult patients with gastric cancer.
The number of older individuals has augmented with increased life expectancy in developed countries. In particular, older adults have become the dominant group of patients with gastric cancer with Helicobacter pylori infection, the main cause of gastric cancer, being more prevalent among the older adult population of East Asia (1). Older adult patients generally include individuals who are frail and afflicted by a broad range of physiological dysfunctions and comorbidities that are highly correlated with aging. One such major comorbidity is cardiac disease, which involves heart failure and subsequent death.
Heart failure results from insufficient cardiac output and is often associated with decreased left ventricular ejection fraction (LVEF), or left ventricular systolic dysfunction (LVSD), in addition to various symptoms. Heart failure and LVSD correlate with a shortened long-term prognosis (2), and heart failure has long been recognized as a risk factor for postoperative mortality (3, 4). Additionally, LVSD has been reported as a risk factor for postoperative mortality (5, 6). Therefore, preoperative screening for LVSD is crucial.
Nevertheless, the impact of preoperative LVSD on the short- and long-term outcomes in older adult patients with gastric cancer has not been elucidated. In the current study, we aimed to evaluate the postoperative complications and prognosis in older adult patients with gastric cancer and LVSD and compare them with those in older adult patients with gastric cancer without LVSD.
Patients and Methods
Study population. A total of 237 consecutive patients, aged ≥75 years, who underwent curative gastrectomy for gastric cancer and preoperative echocardiography between 2013 and 2017 at the Saitama Medical University International Medical Center were enrolled in this study. Prognosis and postoperative complications were compared in patients with (low-EF group) and without (normal-EF group) LVSD. Patient clinicopathological data and clinical courses were retrospectively collected from hospital records.
Study criteria. LVSD was defined as LVEF <50% as measured using echocardiography, irrespective of past cardiac diseases (5). Tumor staging was performed according to the Union for International Cancer Control/Tumour-Node-Metastasis (UICC/TNM) staging system, 8th edition (7). Preoperative comorbidities were classified using the Charlson comorbidity index (CCI) score (8). Postoperative complications were evaluated using the Clavien–Dindo (CD) classification (9), and complications with CD ≥2 within 30 days after operation were defined as postoperative complications in this study. Postoperative surveillance was conducted in accordance with the Japanese Gastric Cancer Treatment Guidelines (10). Blood tests and computed tomography (CT) were performed every 6 months and esophagogastroduodenoscopy was conducted annually. In the patients with gastric cancer, tegafur/gimeracil/oteracil monotherapy was implemented as postoperative adjuvant chemotherapy for stage II/III gastric cancer based on the patient’s consent and general condition (10). The median follow-up period was 4.9 years.
Statistical analysis. Statistical analyses were performed using JMP, version 14 (SAS Institute, Cary, NC, USA). Fisher’s exact test or the chi-square test was used to evaluate differences in proportions, and the Wilcoxon test was used to evaluate continuous variables. Survival outcomes were analyzed using the Kaplan–Meier method, and differences were assessed using log-rank test. Cox regression analysis was used to perform multivariate analyses using covariates with a significance level of p<0.05. In all analyses, a value of p<0.05 was considered statistically significant.
Ethical statements. The procedures conducted in this study adhered to the ethical standards of the Institutional Research Committee and the 1964 Declaration of Helsinki, along with its later amendments or comparable ethical standards. The study protocol was reviewed and approved by the Independent Ethics Committee of the Saitama Medical University International Medical Center (approval number: 19226). Informed consent was obtained from all the participants.
Results
Clinical characteristics in patients with or without LVSD. Among the 237 patients, 13 (5.4%) showed abnormal indexes with LVEF <50% (low-EF group), and the remaining patients had no LVSD (normal-EF group). The clinical characteristics of the two groups are summarized in Table I. The low-EF group had a greater number of smokers and patients with history of ischemic heart disease and higher CCI scores than those of the normal-EF group did. None of the patients in the low-EF group received adjuvant chemotherapy, whereas 28 patients in the normal-EF group received the treatment. A summary of postoperative complications is shown in Table II. No statistically significant difference in the incidence of postoperative complications was observed between the two groups (low-EF group, 30.7% vs. normal-EF group, 21.8%; p=0.470). However, the incidence of postoperative pneumonia was higher in the low-EF group than in the normal-EF group (low-EF group, 30.7% vs. normal-EF group, 4.4%; p=0.003). No cardiac complications were observed in either of the groups. One and four patients died within 90 days postoperatively in the low-EF and normal-EF groups, respectively.
Clinical characteristics of 237 patients included in the study.
Summary of postoperative complications (Clavien–Dindo ≥2) in older adult patients with gastric cancer.
Survival outcomes and the prognostic impact of LVSD. The 5-year overall survival (OS) curves for both the groups are shown in Figure 1; the 5-year OS of low-EF and normal-EF groups were 38.1% and 71.7%, respectively, with the low-EF group having a significantly worse prognosis (p=0.016) than the normal-EF group. The 5-year cancer-specific survival (CSS) and non-CSS curves for both the groups are shown in Figure 2a and b, respectively. Although no statistically significant difference in the 5-year CSS was observed between the two groups (low-EF group, 64.6% vs. normal-EF group, 81.1%; p=0.212), the 5-year non-CSS showed that low-EF group had a significantly worse prognosis than the normal-EF group (low-EF group, 58.9% vs. normal-EF group, 88.3%; p=0.020).
Overall survival in patients with normal-EF and those with low-EF. EF: Ejection fraction.
Cancer-specific (a) and non-cancer-specific (b) survival in patients with normal-EF and those with low-EF. EF: Ejection fraction.
Additionally, prognostic factors influencing OS were evaluated (Table III). Univariate analysis revealed that low preoperative body mass index (BMI), history of ischemic heart disease, high CCI scores, advanced pathological stage, and low LVEF were significant prognostic factors for low OS. Furthermore, multivariate analysis revealed that low preoperative BMI, advanced pathological stage, and low LVEF were independent prognostic factors for low OS [low preoperative BMI, hazard ratio (HR)=1.84, p=0.019; advanced pathological stage, HR=4.66, p<0.001; low LVEF, HR=3.23, p=0.025].
Analysis of risk factors of overall survival in older adult patients with gastric cancer.
Discussion
The present study demonstrates that the presence of preoperative LVSD was associated with an increased incidence of postoperative pneumonia, but not with other complications. However, LVSD has a negative prognostic impact and is a significant prognostic factor, similar to low BMI and advanced pathological stage (11). Given the absence of literature exploring the effect of preoperative LVSD on prognosis in older adult patients with gastric cancer, the current study is the first to demonstrate the clinical impact of LVSD on the short- and long-term outcomes in this group of patients.
Previous studies have shown that heart failure is a significant risk factor for perioperative cardiac complications in noncardiac surgery (3, 6, 12, 13). Thomas et al. identified a history of heart failure as an independent predictor of surgical complications (3). Healy et al. also reported that severely decreased LVEF is a risk factor for adverse outcomes within 30 days of noncardiac surgery (6). In this study, the incidence of postoperative pneumonia was higher in the low-EF group than in the normal-EF group, whereas no significant differences were observed in terms of other postoperative complications. One reason is the inability to cope with perioperative fluid shifts and stress, which has been identified to increase complications in patients with heart failure (14). Moreover, general anesthesia in patients with heart failure can cause intraoperative and postoperative hypotension (5), which may reduce blood perfusion to the lungs and increase the incidence of pneumonia. In addition, Testa et al. reported that heart failure increased cytokines and other inflammatory mediators (15), which may lead to the immune dysregulation and increase the incidence of pulmonary complications. Thus, careful treatment is required in patients with LVSD during the perioperative period.
In the present study, we demonstrated a significantly worse long-term prognosis in patients with gastric cancer and LVSD than in those without LVSD. Benjamin et al. observed that a low LVEF increased the postoperative 30-day, 90-day, and 1-year mortality in noncardiac surgery (5), and Healy et al. reported that LVEF is an independent risk factor for long-term mortality (6). Putative contributing factors may be explained by the fact that patients with heart failure are less likely to tolerate postoperative complications, thus reducing their long-term survival (5). Postoperative pneumonia following gastrectomy has been reported to have an adverse effect on the long-term survival in older adult patients with gastric cancer (16). In the present study, the 5-year OS in the older adult patients in the low-EF group was 0% for those with postoperative pneumonia, whereas that in patients without complications was 72.9% (p=0.083). In addition, the 5-year CSS did not differ significantly between the two groups, while the 5-year non-CSS had a significantly worse prognosis in the low-EF group than in the normal-EF group, suggesting that great emphasis should be placed on care not only for gastric cancer but also for other diseases. Therefore, preventing postoperative complications and providing adequate management for other complications may be critical in older adult patients with gastric cancer and LVSD than in those without LVSD.
Additionally, accelerated sarcopenia may result in poor prognosis in patients with LVSD. Sarcopenia is a state of decreased skeletal muscle mass, muscle strength, and physical function (17). The association between sarcopenia and any cause of death has recently been proven in large cohort studies (18, 19). Gastrectomy causes weight and skeletal muscle mass loss due to decreased oral intake and nutrient malabsorption. Heart failure also results in reduced weight and skeleton muscle mass, a condition termed “cardiac cachexia” (20). Moreover, gastric cancer itself induces cachexia, or so-called “cancer cachexia.” Thus, the vicious cycle of heart failure, gastric cancer, and gastrectomy may accelerate sarcopenia and cachexia in patients with LVSD. Post-gastrectomy nutritional therapy in patients has been reported to attenuate weight loss (21, 22), and regular aerobic exercise has been documented to have beneficial effects on cardiac function (23). In addition, because concurrent dietary and exercise therapy is effective against sarcopenia (24), perioperative nutritional and exercise therapies might improve outcomes in patients with LVSD.
In lung and breast cancer, radiation therapy is one of the main treatment modalities. Despite several techniques to avoid cardiac injury, including stereotactic ablative radiotherapy (25), radiotherapy-induced cardiac injury remains a major problem. Recently, global longitudinal strain (GLS) was reported to be useful in predicting radiation-induced heart damage in breast cancer (26). This index has been reported to be more sensitive than LVEF for predicting LVSD after myocardial infarction (27). Thus, the GLS may be as useful as LVEF in predicting postoperative complications and prognosis in older adult patients with gastric cancer.
Study limitations. First, none of the patients with LVSD received adjuvant chemotherapy, which may have affected their prognosis. However, no study has yet proven the benefit of adjuvant chemotherapy for older adult patients with gastric cancer, and no significant difference in the 5-year CSS was observed in this study. Second, patients with LVSD had higher CCI scores, were more likely to smoke, and had a history of ischemic heart disease. However, univariate and multivariate analyses revealed that these were not prognostic factors in older adult patients with gastric cancer. Therefore, the effects of such biases were considered to be relatively small. Third, this was a single-center, retrospective study. Further studies with larger prospective cohorts are required to obtain more compelling results.
Conclusion
In conclusion, the presence of preoperative LVSD did not increase postoperative complications but independently negatively affected survival outcomes in older adult patients with gastric cancer. Although curative gastrectomy can be safely performed in patients with LVSD, it requires careful postoperative management as even minor complications can aggravate their prognosis.
Footnotes
Authors’ Contributions
Study conception design by KT, SS and KY. Data acquisition by KT, RK, TT and GE. Data analysis and interpretation by all authors. Drafting the article by KT, SS and KY. Critical revision for intellectual content by all authors. All Authors approved of the final manuscript and agreed to be accountable for all aspects of work.
Conflicts of Interest
The Authors have no competing interests to declare.
- Received September 22, 2024.
- Revision received October 14, 2024.
- Accepted October 30, 2024.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
