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Abstract
Objectives The clinical outcomes of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis (AS) and concomitant active cancer remain insufficiently explored. This study aimed to assess the midterm outcomes of TAVR in patients diagnosed with AS and active cancer.
Methods Data from the OCEAN-TAVI, a prospective Japanese registry of TAVR procedures, was analysed to compare prognoses and clinical outcomes in patients with and without active cancer at the time of TAVR.
Results Of the 2336 patients who underwent TAVR from October 2013 to July 2017, 89 patients (3.8%) had active cancer, whereas 2247 did not. Among patients with active cancer, 49 had limited-stage cancer (stage 1 or 2). The prevalent cancers identified before TAVR were colon (21%), prostate (18%), lung (15%), liver (11%) and breast (9%). Although the periprocedural complications and 30-day mortality rates were comparable between the groups, the 3-year survival rate after TAVR was notably lower in patients with active cancer (64.7%) than in those without active cancer (74.7%; p=0.016). Nevertheless, the 3-year survival rate of patients with limited-stage cancer (stage 1 or 2) did not significantly differ from those without cancer (70.6% vs 74.7%, p=0.50).
Conclusions The patients with active cancer exhibited significantly reduced midterm survival rates. However, no distinct disparity existed in those with limited-stage cancer (stage 1 or 2). Although TAVR is a viable treatment in patients with AS with active cancer, the type and stage of cancer and prognosis should be carefully weighed in the decision-making process.
- aortic valve stenosis
- transcatheter aortic valve replacement
- heart valve diseases
Data availability statement
No data are available. The data in this research are deidentified participant data. The data and materials will not be available to researchers for purpose of reproducing the results or replicating the procedure.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Transcatheter aortic valve replacement (TAVR) has been established as the primary treatment modality for improving clinical outcomes in patients with aortic stenosis (AS) at all surgical risks. However, patients with active cancer have been largely excluded from pivotal TAVR trials due to concerns about their relatively short and unpredictable life expectancies. Therefore, the clinical outcomes of TAVR in patients with AS and concomitant active cancer remain insufficiently explored.
WHAT THIS STUDY ADDS
Based on a Japanese multicentre prospective registry, although patients with active cancer exhibited significantly reduced midterm survival rates, no distinct disparity exists in those with limited-stage cancer (stage 1 or 2).
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
In the decision-making process, the decision to perform TAVR in patients with active cancer should be made after careful consideration of cancer type, stage and prognosis by an integrated heart team including oncologists.
Introduction
Cancer is the leading cause of death in Japan; the number of cases is increasing annually. The prevalence of aortic stenosis (AS) and cancer increases with age, and these conditions are often comorbid. Transcatheter aortic valve replacement (TAVR) has been established as the primary treatment modality for improving clinical outcomes in patients with AS at all surgical risks.1–6 Patients with active cancer are often considered suitable candidates for TAVR due to the high burden of comorbidities. However, patients with active cancer have been largely excluded from pivotal TAVR trials due to concerns about their relatively short and unpredictable life expectancies.1 4 The current guidelines recommend valve intervention in patients with AS only if their life expectancy exceeds 12 months.7 8 In clinical settings, prognostically assessing patients with active cancer concomitant with severe AS often presents challenges for both the heart team and oncologists. Improvements in severe AS may allow for more aggressive cancer treatment and provide symptom relief. However, data on the outcomes of TAVR in patients with AS and concomitant active cancer, particularly beyond 1 year, remain limited.9 10 This study aimed to evaluate midterm outcomes of TAVR in this patient group.
Methods
Study population and design
The Optimized CathEter vAlvular iNtervention (OCEAN)-TAVI registry is an ongoing prospective, investigator-initiated, multicentre, observational registry of patients undergoing TAVR in Japan. The trial was registered with the University Hospital Medical Information Network (UMIN000020423). From October 2013 to July 2017, 2588 patients with severe AS underwent TAVR procedures at 14 institutions included in the OCEAN-TAVI registry. The selection of TAVR was based on clinical consensus among centres and consultations within the heart team. Patient selection was left to the discretion of each centre. However, patients with a prognosis at less than 1 year, severe dementia or bedridden status were excluded. After excluding 252 patients due to a lack of patient information, we enrolled 2336 patients from 11 institutions and divided them into two groups: with and without active cancer at the time of the procedure. In addition, we divided the patients with active cancer into limited-stage (stage 1 or 2) and advanced-stage (stage 3 or 4) cancer groups to assess the impact of cancer progression on survival. In this study, a balloon-expandable Edwards Sapien XT/Sapien S3 prosthesis (Edwards Lifesciences, Irvine, California, USA) or a Medtronic CoreValve/Evolut R prosthesis (Medtronic, Minneapolis, Minnesota, USA) was used. The prosthesis type, size and approach site were determined based on the procedural echocardiography and multidetector CT findings. Intraoperative and other adverse events were evaluated according to the Valve Academic Research Consortium-2 criteria.11 Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.
Definitions of active cancer and data collection
Active cancer was diagnosed by a specialised oncologist and included patients where cancer had not been cured, who were undergoing cancer-related treatment, and who had active metastatic disease or recurrence of active cancer. We prospectively obtained clinical data, including patient characteristics, operative risk, echocardiographic data, procedural data, in-hospital outcomes and long-term outcomes from the OCEAN-TAVI registry database. In addition, cancer information including type, stage and metastatic status was obtained through outpatient visits or telephone interviews with all patients.
Clinical endpoints and statistical analysis
The primary endpoint was the 3-year survival rate after TAVR. Normally distributed continuous variables are reported as mean±SD and were compared using the Student’s t-test. Categorical variables are described as frequencies and were compared using the χ2 test. Time-to-event data are presented as Kaplan-Meier estimates and were compared using the log-rank test. Differences were considered statistically significant at a two-sided p<0.05. Statistical analyses were performed using the R V.4.1.2 (R Foundation for Statistical Computing, Vienna, Austria).
Results
Study population and baseline clinical characteristics
Between October 2013 and July 2017, we enrolled 2336 patients with severe AS who underwent TAVR. The baseline characteristics are summarised in table 1. In this study, 89 (3.8%) patients had active cancer. The patients with active cancer were younger and more often male participants. Body surface area and body mass index were higher in patients with active cancer compared with those without cancer. The patients with active cancer had a high prevalence of liver diseases. Operative risk scores, including the Society of Thoracic Surgeons score and European Systems for Cardiac Risk Evaluation II, were significantly lower in patients with active cancer. Echocardiographic data showed that the patients with active cancer were more likely to have a larger aortic valve area and better left ventricular ejection fraction. Other baseline comorbidities were similar between both groups.
Study population and procedural findings
Type and stage of cancer
Figure 1 shows the types of cancer in patients with active cancer. Three patients had multiple cancers and were categorised according to the most advanced stage of their cancers. Of the patients with active cancer (89 patients), 85 had known cancer staging before TAVR, including 23, 26, 16 and 20 patients with stages 1, 2, 3 and 4, respectively.
Cancer types in patients with active cancer (n=89). The most common cancers diagnosed prior to TAVR are colon (21%), prostate (18%), lung (15%), liver (11%) and breast (9%) cancers. TAVR, transcatheter aortic valve replacement.
Procedural characteristics and outcomes
The procedural characteristics and outcomes are summarised in tables 1 and 2. There were no differences in the approach site, valve type or valve size between the two groups. The incidences of major and minor vascular complications and life-threatening or major bleeding were similar in both groups. There were no differences in the incidence of other complications, including acute kidney injury, myocardial infarction, ischaemic stroke and new pacemaker implantation. The 30-day mortality rate was 0% in patients with active cancer, with no apparent difference compared with those without cancer (1.9%).
Procedural outcomes
Overall survival following TAVR
The median follow-up duration was 716 days (IQR 384–917 days). As shown in figure 2, the 3-year survival rate after TAVR was significantly lower in patients with active cancer than in those without active cancer (p=0.016). Among the patients with active cancer (89 patients), the patients with limited-stage cancer (49 patients) (stage 1 or 2) showed no significant difference in the 3-year survival rate compared with those without cancer (p=0.50) (figure 3). Of the patients with active cancer, 43 (46.2%) died during the follow-up period. Half of the deaths were related to cancer (21 cases), whereas 16% (7 cases) were due to cardiovascular causes. One-year survival rates according to cancer type are shown in figure 4, indicating that survival rates vary by cancer type. Furthermore, some types of cancer resulted in adequate 1-year survival even with advanced-staged cancer. Table 3 lists the 13 patients who died within 1 year after TAVR. Most of these patients had advanced-stage cancer and were scheduled for postoperative cancer treatment but died within a year due to cancer progression or infection.
Kaplan-Meier survival curves in patients with and without cancer. The overall survival rate is significantly different between patients with and without cancer (log-rank test, p=0.016).
Kaplan-Meier survival curves in patients with limited-stage cancer or without cancer. The overall survival rate was not significantly different between the patients with stage 1 or 2 cancer and those without cancer (log-rank p=0.50).
One-year survival rates by cancer type.
Detailed characteristics of the patients who died within 1 year after TAVR
Discussion
The findings of the present study were: first, baseline characteristics were similar in patients with and without active cancer, and surgical risk scores were rather low in those with cancer. Second, TAVR was safe in patients with active cancer, with similar periprocedural complication rates and 30-day mortality compared with those without cancer. Third, active cancer was significantly associated with increased mortality during the midterm follow-up period. Fourth, prognosis varied by cancer type, and death within 1 year after TAVR was not uncommon in patients with active cancer. Fifth, in patients with limited-stage cancer, there was no clear difference in the 3-year survival rate compared with those without cancer.
The impact of active cancer on patient prognosis following TAVR is still debatable.9 10 12 13 In previous work, our group reported that survival rates in patients with active cancer and severe AS undergoing TAVR were similar to those without active cancer, irrespective of the cancer status.9 The current study could advance our understanding by offering a longer follow-up and a larger patient cohort. In the present study, active cancer was significantly associated with increased mortality during the midterm follow-up period despite favourable periprocedural or short-term results. This result is consistent with that of recent meta-analyses.14 15 Patients eligible for TAVR are estimated to have a life expectancy of at least 1 year after treatment.7 8 Even patients with AS and concomitant active cancer who choose to undergo TAVR are generally younger and at lower risk compared with those without cancer, which may lead to better short-term outcomes. Furthermore, TAVR may positively impact anticancer therapy by enhancing a patient’s health status and overall quality of life.3 6 However, in terms of long-term outcomes, patients with active cancer exhibited a lower long-term survival rate than did those without cancer, primarily due to ongoing cancer-related factors (progression, metastasis and recurrence). In this study, half of deaths were associated with cancer. However, for a limited number of cancers, appropriate post-TAVR cancer treatment may lead to favourable midterm outcomes. Notably, there was no significant difference in the 3-year survival rates between patients with and without cancer. Naturally, the cancer type also significantly affects patient prognosis. The 5-year relative survival rates for various cancers in Japan are as follows: 71.4% (colon), 99.1% (prostate), 35.8% (liver), 34.9% (lung) and 92.3% (breast).16 17 Even when examining the 1-year survival in this study, the survival rate varied greatly depending on the type of cancer.
The current guidelines recommend postponing or cancelling non-cardiac surgeries in patients with symptomatic severe AS. Surgical aortic valve replacement (SAVR) or TAVR is advised before non-cardiac surgeries, including cancer surgeries.7 8 TAVR can be safely performed even in patients with cancer to facilitate aggressive cancer therapy. However, there are many patients for whom planned postoperative treatment cannot be performed due to cancer progression or who experience early death due to cancer progression, even after treatment. Hence, a multidisciplinary approach involving the heart team, including oncologists, is crucial for a thorough evaluation of TAVR indications in patients with cancer. TAVR should not be recommended unless there is a reasonable probability that patients with AS and concomitant active cancer could have more than 1 year to live, as the benefits gained from TAVR may be limited.
Study limitations
We acknowledge several limitations to a thorough understanding of our results. First, we lacked data on patients with and without active cancer who underwent SAVR or received medical therapy. Particularly, patients with active cancer who undergo TAVR might represent a highly selected group. Consequently, the findings of this study cannot be generalised to all patients with AS and active cancer. Second, we did not have data on quality of life, which is a particularly critical outcome measure for patients with active cancer, as they were not available. Third, since the percentage of patients with active cancer and types of cancer varied among the institutions, the impact of differences cannot be ignored. Furthermore, the retrospective observational nature of this study carries inherent limitations.
Conclusions
This study indicated that, although the patients with active cancer exhibited significantly reduced midterm survival rates, no distinct disparity existed in those with limited-stage cancer (stage 1 or 2). Performing TAVR in patients with active cancer might necessitate a thorough deliberation of cancer prognosis by an integrated heart team including oncologists.
Data availability statement
No data are available. The data in this research are deidentified participant data. The data and materials will not be available to researchers for purpose of reproducing the results or replicating the procedure.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by the Institutional Review Board of Tokyo Bay Urayasu Ichikawa Medical Center (ID: 2016268). Written informed consent was obtained from all patients before the TAVR procedure.
Acknowledgments
The authors thank the investigators and institutions that participated in the OCEAN-TAVI registry.
References
Footnotes
Collaborators The OCEAN-TAVI investigators.
Contributors Study conception, design, analysis and interpretation, drafting of the manuscript—MN, MT and JI. Critical revision of the manuscript for important intellectual content—NK, KO, HW, FY, YW, TN, MY, FY, SS, HU, NT, MY and KH. Responsible for the overall content as the guarantor—MT.
Funding The OCEAN-TAVI registry is supported by Edwards Lifesciences, Medtronic, Boston Scientific, Abbott Medical and Daiichi-Sankyo Company.
Competing interests MT, TN and HU are clinical proctors at Edwards Lifesciences and Medtronic. MY, SS, NT, HW and KH are clinical proctors at Edwards Lifesciences, Abbott Medical and Medtronic. FY is a clinical proctor at Medtronic.
Provenance and peer review Not commissioned; externally peer reviewed.