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Cardiooncology
Cardiooncology
Cardio-oncology
2057-3804
BioMed Central London

39252142
256
10.1186/s40959-024-00256-8
Research
Outcomes of patients with active cancer after transcatheter aortic valve replacement: an updated meta-analysis
Felix Nicole nicole.santos@estudante.ufcg.edu.br

1
Nogueira Alleh 2
Carvalho Pedro E. P. 3
Costa Thomaz Alexandre 4
Tramujas Lucas 5
Generoso Giuliano 6
Feldman Stephanie 7
Garot Philippe 8
de Farias Maria do Carmo Andrade Duarte 1
1 https://ror.org/00eftnx64 grid.411182.f 0000 0001 0169 5930 Division of Medicine, Federal University of Campina Grande, 795 Juvêncio Arruda Avenue, Campina Grande, Brazil
2 https://ror.org/0300yd604 grid.414171.6 0000 0004 0398 2863 Division of Medicine, Bahiana School of Medicine and Public Health, Salvador, Brazil
3 https://ror.org/03mhcky17 grid.480845.5 0000 0004 0629 5065 Center for Coronary Artery Disease, Minneapolis Heart Institute Foundation, Minneapolis, USA
4 https://ror.org/04cqn7d42 grid.499234.1 0000 0004 0433 9255 Department of Medicine, University of Colorado School of Medicine, Aurora, CO USA
5 grid.477370.0 0000 0004 0454 243X Hcor Research Institute, São Paulo, Brazil
6 https://ror.org/03r5mk904 grid.413471.4 0000 0000 9080 8521 Division of Cardiology, Hospital Sírio-Libanês, São Paulo, Brazil
7 https://ror.org/02r109517 grid.471410.7 0000 0001 2179 7643 Division of Cardiology, Department of Internal Medicine, Weill Cornell Medicine, New York, NY USA
8 https://ror.org/0453c4485 grid.418134.b Institut Cardiovasculaire Paris Sud (ICPS), Hôpital Jacques Cartier, Ramsay-Santé, Massy, France
2 9 2024
2 9 2024
2024
10 5517 3 2024
12 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

Patients with active cancer and aortic stenosis may be under-referred for valve interventions due to concerns over a prohibitive risk. However, whether active cancer impacts outcomes after transcatheter aortic valve replacement (TAVR) remains unknown.

Methods

We searched PubMed, Embase, and Cochrane Library in December 2023 for studies comparing the post-TAVR outcomes of patients with versus without active cancer. We pooled odds ratios (OR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) applying a random-effects model. Statistical analyses were performed in R version 4.3.2.

Results

We included nine observational studies analyzing 133,906 patients, of whom 9,792 (7.3%) had active cancer. Compared with patients without cancer, patients with active cancer had higher short- (OR 1.33; 95% CI 1.15–1.55; p < 0.001) and long-term mortality (OR 2.29; 95% CI 1.80–2.91; p < 0.001) rates, not driven by cardiovascular mortality (OR 1.30; 95% CI 0.70–2.40; p = 0.40), and higher major bleeding rates (OR 1.66; 95% CI 1.15–2.42; p = 0.008). The higher mortality rate was sustained in an adjusted analysis (aHR 1.77; 95% CI 1.34–2.35; p < 0.001). There was no significant difference in cardiac, renal, and cerebral complications at a follow-up ranging from 180 days to 10 years.

Conclusion

Patients with active cancer undergoing TAVR had higher non-cardiovascular mortality and bleeding rates, with comparable incidences of other complications. This highlights the need for a shared decision and appropriate patient selection considering cancer type, staging, bleeding risk, and optimal timing for intervention.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1186/s40959-024-00256-8.

Keywords

Aortic valve stenosis
Cardio-oncology
Meta-analysis
Neoplasms
Transcatheter aortic valve replacement
issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcIntroduction

Cardiovascular disease and cancer often coexist given their shared risk factors and underlying pathophysiology [1]. As cancer therapies evolve and improve life expectancy, cancer survivors may experience an excess risk of cardiovascular disease due to a longer exposure to risk factors and chronic inflammation [2]. This is especially true for aortic stenosis, the most prevalent non-rheumatic valvular heart disease, which already has a prevalence as high as 12.4% among the elderly [3, 4].

Severe aortic stenosis is a malignant disease itself, with mortality rates reaching 68% in 2 years if left untreated, comparable or even higher than cancer depending on type and stage [5, 6]. Current Interventional Cardiology and Cardio-Oncology guidelines recommend decision on surgical versus transcatheter aortic valve replacement (TAVR) considering predicted life expectancy, prognosis, and patient preferences [7, 8]. However, many patients with active cancer are under-referred for valve surgery allegedly due to a prohibitive surgical risk [6, 9], even though cancer itself is not accounted for by surgical risk calculators [10].

Moreover, the outcomes of patients with active cancer after TAVR remain unknown, since pivotal device trials excluded patients deemed to have a short life expectancy [11]. Importantly, patients with a history of cancer might have unpredictable outcomes after cardiovascular interventions [12], and their prognosis should not be extrapolated from other populations without proper assessment.

Prior meta-analyses examined the post-TAVR outcomes of patients with either active [13] or previous cancer [14–16], while another evaluated only patients with radiation-associated aortic stenosis [17]. However, their pooled populations were either small or heterogeneous in terms of cancer status, which may have impaired the statistical power and generalizability of their findings. To address this, we performed an updated meta-analysis restricted to patients with active cancer versus patients without cancer to assess their post-TAVR outcomes, aiming to determine whether active cancer significantly impacts short and long-term outcomes.

Methods

We performed this systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines [18]. As such, the protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) database under registration number CRD42024498516. There was no requirement for informed consent or Institutional Review Board approval for this meta-analysis, given that the data are publicly available and we did not have access to individual patient data.

Eligibility criteria

We restricted inclusion in this meta-analysis to the following eligibility criteria: (1) randomized and non-randomized studies, either prospective or retrospective; (2) that compared patients with versus without active cancer; (3) undergoing TAVR; and (4) reporting any of the Valve Academic Research Consortium 3 (VARC-3) proposed clinical endpoints, as reported below [19]. All patients underwent TAVR, and therefore the exposure was active cancer, and the control group was composed of patients without active malignancy.

We excluded studies that included only cancer survivors with a remote history of malignancy, studies that did not have a control group, or articles that compared TAVR versus surgical aortic valve replacement or combined procedures (e.g., percutaneous coronary intervention and TAVR). We also excluded studies with overlapping patient populations, studies published only as conference abstracts, and case reports/series.

Search strategy and data extraction

We systematically searched PubMed, Embase, and Cochrane Library from inception to December 26, 2023 using the following medical subject heading terms: transcatheter aortic valve replacement, transcatheter aortic, percutaneous aortic, TAVR, TAVI, cancer, malignancy, tumor, and neoplasms. The full search string is available in the Supplemental Material. Additionally, we performed a backward snowballing search for eligible studies in the references section of included studies and relevant literature reviews.

Three authors (N.F., A.N., and P.E.P.C.) independently extracted data following predefined search criteria and quality assessment methods. Disagreements among authors were resolved through consensus.

Endpoints and subanalyses

The analyzed outcomes may be stratified according to follow-up as short- and long-term endpoints, as well as endpoints with adjustment for confounders. The short-term outcomes included mortality (defined as either in-hospital or 30-day mortality) and other VARC-3 complications, namely: (1) need for permanent pacemaker implantation; (2) major bleeding, defined as bleeding requiring transfusion or life-threatening bleeding as per study definition; (3) stroke; (4) myocardial infarction; (5) acute kidney injury (AKI); (6) major vascular complications; (7) and post-TAVR aortic valve gradient.

Second, we examined long-term mortality at the longest follow-up available in each individual study and cardiovascular mortality. Finally, we evaluated mortality with adjustment for potential confounding, and likewise we assessed mortality among patients with advanced cancer (stage III to IV or metastasis), as available in the included studies.

Statistical analysis

We performed all analyses as per Cochrane recommendations [20]. A random-effects model was applied to account for demographical and methodological between-study heterogeneity. We pooled odds ratios (ORs) with 95% confidence intervals (CI) for binary endpoints and mean differences (MD) with 95% CI for continuous outcomes, respectively. In continuous outcomes for which studies reported only medians (interquartile ranges), we estimated corresponding means ± standard deviations by applying the method by Wan and Luo [21]. To preserve time-to-event data and adjust for potential confounders, we pooled adjusted hazard ratios (aHR) with 95% CI estimated by multivariate analyses, propensity score matching, or multivariable adjusted models. Other aHR were also pooled if available in the individual studies.

P-values inferior to 0.05 were deemed statistically significant in the overall analyses. We assessed between-study heterogeneity through Cochran’s Q test and I2 statistics; p-values less than 0.10 and I2 ≥ 25% were considered significant for heterogeneity. All statistical analyses were performed using R version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria).

Quality assessment

Two authors (T.A.C. and A.N.) assessed risk of bias in the non-randomized prognostic studies with the Quality in Prognosis Studies (QUIPS) tool, which allows labeling studies as low, moderate, or high risk of bias in six domains: study participation, study attrition, prognostic factor measurement, outcome measurement, study confounding, and statistical analysis and reporting [22]. Disagreements were resolved through consensus among authors. In addition, we assessed small study effects (potentially attributable to publication bias) through funnel plot analysis for the outcome of long-term mortality.

Results

Study selection and pooled population characteristics

As depicted in Supplementary Fig. 1, our initial search yielded 1,541 records. After removal of duplicate reports and screening based on title and/or abstract, we selected 43 studies for review in full. Ten studies met our inclusion criteria [6, 12, 23–30], but two had overlapping populations [12, 24]. Therefore, we included the one comprising the largest population and number of available outcomes [12]. Reasons for exclusion of full-texted reviewed studies are available in the Supplementary Material.

Study characteristics are displayed in Table 1. The nine studies comprised 133,906 patients, of whom 9,792 (7.3%) had active cancer. Three studies were prospective cohorts, and six were retrospective cohort studies. The longest follow-up available and analyzed ranged from 180 days to 10 years. The pooled population was mostly composed of older patients, as the average age ranged from 78.5 to 85 years. The prevalence of hypertension was high (87.6%). 47.3% were female. The mean aortic valve area ranged from 0.6 to 0.7 cm2. Of note, we used data from registries including patients at various surgical risks, with an average Society of Thoracic Surgeons score ranging from 4.4 to 7 points.

Only two studies included patients with skin cancers and did not state whether these were non-melanoma skin tumors [29, 30]. However, these accounted for only up to 7.5% of all malignancies in each study and six cases in total, with a minimal impact on a cohort of 9,792 patients with active cancer. Representativity of cancer types and definitions of active cancer in each study are displayed in Supplementary Tables 1 and 2, respectively.

Mortality

Active cancer was associated with significantly higher short-term all-cause mortality rates as compared with no cancer (pooled OR 1.33; 95% CI 1.15–1.55; p < 0.001; I2 = 1%; Fig. 1A). This was sustained at the longest follow-up available (pooled OR 2.29; 95% CI 1.80–2.91; p < 0.001; I2 = 26%; Fig. 1B). The higher all-cause mortality was apparently driven by non-cardiovascular causes, for there was no significant difference between groups in cardiovascular mortality (pooled OR 1.30; 95% CI 0.70–2.40; p = 0.405; I2 = 49%; Fig. 2).

Upon analysis using aHR as available in the included studies, patients with active cancer remained at a significantly higher risk for all-cause mortality (aHR 1.77; 95% CI 1.34–2.35; p < 0.001; I2 = 71%; Fig. 3A), with a high between-study heterogeneity. As expected, the risk was even higher among patients with active advanced stage malignancies (aHR for mortality in stage III to IV or metastasis 3.39; 95% CI 2.54–4.52; p < 0.001; I2 = 0%; Fig. 3B).

VARC-3 outcomes

Active cancer was associated with significantly higher major bleeding rates relative to no cancer (pooled OR 1.66; 95% CI 1.15–2.42; p = 0.008; Fig. 4). Of note, there was a high between-study heterogeneity in this outcome (I2 = 58%).

There was no significant difference between groups in terms of post-procedural stroke (pooled OR 0.96; 95% CI 0.58–1.59; p = 0.880; I2 = 0%; Supplementary Fig. 2A), myocardial infarction (pooled OR 1.99; 95% CI 0.98–4.01; P = 0.56; I2 = 0%; Supplementary Fig. 2B), AKI (pooled OR 1.26; 95% CI 0.97–1.63; p = 0.083; I2 = 0%; Supplementary Fig. 3A), need for permanent pacemaker implantation (pooled OR 1.17; 95% CI 0.84–1.63; p = 0.352; I2 = 0%; Supplementary Fig. 3B), major vascular complications (pooled OR 1.02; 95% CI 0.37–2.83; p = 0.966; I2 = 0%; Supplementary Fig. 3C), or aortic valve gradient (weighted MD 1.38 mmHg; 95% CI -0.34 to 3.11 mmHg; p = 0.116; I2 = 89%; Supplementary Fig. 4).

Quality assessment

We conducted a risk of bias assessment for the included prognostic studies using the QUIPS tool. All studies were categorized with an overall moderate risk of bias. The primary factor contributing to this assessment across the included studies was a moderate risk of bias associated with the domain of study confounding. The individual study appraisal of all domains is presented in Supplementary Fig. 5. Through funnel plot assessment, no evidence of a small study effect attributable to publication bias was observed, as studies with similar weights were symmetrically distributed against their standard errors (Supplementary Fig. 6).

Discussion

In this meta-analysis of nine observational studies, we compared the short and long-term outcomes of patients with versus without active cancer after TAVR for severe aortic stenosis, most of them at intermediate surgical risk. Our main findings were as follows: (1) higher short- and long-term mortality rates driven by non-cardiovascular causes in patients with active cancer, which remained consistent after adjustment for confounders; (2) mortality was even higher among those with active advanced stage malignancies (stage III or higher); (3) there was a higher incidence of post-TAVR major bleeding in patients with active cancer, not driven by major vascular complications; and (4) no significant difference between groups in terms of aortic valve gradient or procedural complications such as stroke and myocardial infarction.

Up to 37.8% of patients with a history of cancer develop aortic stenosis [31]. The coexistence of these two conditions may ultimately impair the management of both of them, considering that patients with anticipated low life expectancy are under-referred for valve interventions and those with severe valvular heart disease may be ineligible for first-line cancer therapies [32]. This raises concerns over the existence of a treatment-risk paradox [33], in which the neediest are less likely to receive guideline-directed treatment, especially because the risk-benefit balance for this population might be unclear to physicians.

Over the last twenty years, TAVR has changed how we care for patients with severe aortic stenosis across the spectrum of surgical risk [8, 34–37]. Unfortunately, patients with active cancer were largely excluded from pivotal device trials, as previously mentioned [8, 38]. Consequently, there are limited and conflicting data on the outcomes of patients with active cancer undergoing TAVR [27, 30]. To address this, previous meta-analyses assessed the safety and efficacy of TAVR in patients with versus without cancer. However, most of them included patients with either active cancer or a remote history of malignancy, increasing heterogeneity and decreasing the generalizability of findings [14–16, 39, 40].

Two meta-analyses included analysis with patients with active cancer only, and their findings differed significantly from ours [13, 14]. For instance, one prior meta-analysis [13] found comparable short-term mortality rates regardless of cancer status, whereas ours yielded a higher short-term mortality in patients with active cancer. Possible explanations for this difference include the increase in statistical power provided by our larger population (133,906 patients in the pooled analyses) and differences in cancer type and staging.

In addition, as compared with these meta-analyses [13, 14], our analysis was the first to indicate a higher incidence of major bleeding in patients with active cancer. While this appears not to be driven by major vascular complications, the occurrence of major bleeding through vascular access sites cannot be ruled out, considering that patients with active cancer often have platelet dysfunction, thrombocytopenia, or are under anticoagulation [41]. Even so, the incidence of bleeding has decreased in recent years [42], given the advances in device technology and vascular access, the learning curve in high-volume centers, and the choice for single antiplatelet therapy or direct oral anticoagulants.

Our unadjusted mortality and major bleeding outcomes exhibited significant inter-study heterogeneity (I² ≥ 25%). We hypothesize that this variability is primarily due to the inclusion of patients at varying cancer stages. This is supported by the fact that heterogeneity decreased to zero in a subanalysis restricted to patients with advanced disease, while the representation of cancer types remained consistent across the included studies.

Conversely, significant heterogeneity persisted (I²=71%) in a subanalysis utilizing adjusted data for variables accounted for surgical risk calculators, such as comorbidities. Unfortunately, we cannot rule out that our results still carry unmeasured confounders beyond the varying cancer stages. In addition, it remains uncertain how the inclusion of patients at different stages of cancer have impacted post-TAVR outcomes. To illustrate, it remains unclear whether the higher major bleeding in the cancer group was driven or not by patients with hematological or chemotherapy-treated advanced malignancies, who are more prone to hemorrhagic events. In fact, the presence of an active advanced stage malignancy (stage III or IV), but not an early stage cancer, is a major criterion for bleeding after TAVR [43]. Even so, our diverse patient cohort reflects the real-world setting, where patients with various types and stages of cancer may have a formal indication for TAVR, and whose outcomes have been unknown until now.

The higher short-term mortality rates in patients with active cancer has important implications. It places a dilemma: while the alternative to valve intervention for these patients is exclusive palliative care, the increase in peri-procedural and short-term mortality and complications risks is noteworthy. In our analysis, this increase in short-term mortality was modest, with an OR of 1.33, considering that aortic stenosis and cancer themselves have high mortality rates if left untreated. Notably, the higher mortality may be driven by the underlying malignancy and might be unrelated to the procedure itself in some cases.

In addition, TAVR is associated with a shorter recovery time than surgical aortic valve replacement and may avoid delays in starting or resuming cancer directed therapies [7, 8]. Importantly, TAVR may even be needed for patients to become eligible for cancer surgery after the resolution of severe aortic stenosis [7]. This underscores the need for a shared decision and an appropriate patient selection, considering cancer site and staging, comorbidities, bleeding risk, and main goal of treating the underlying valvular heart disease. That is, whether the symptoms are enough to warrant intervention or if the resolution of aortic stenosis is also crucial for the management of the underlying malignancy.

For reference, patients with active cancer in early stages may benefit from TAVR; nonetheless, they may receive antineoplastic therapy and undergo TAVR when remission is achieved. In contrast, patients with more progressive disease may benefit from a TAVR-first approach to become eligible for more aggressive cancer directed therapies [32]. Of note, waiting for remission to intervene may not be advisable in many cases, considering the risk of aortic stenosis progression. In addition, cancer survivors who recently underwent chemotherapy may be immunocompromised and at a higher risk for bleeding, which might affect post-TAVR outcomes negatively.

To date, the optimal timing for TAVR in this population remains unknown. More importantly, it remains uncertain whether TAVR should be performed at all for subgroups with advanced disease and borderline predicted life expectancy. Given the wide spectrum of illness severity in patients with cancer and the constant improvement of cancer therapies with consequent increased survival, no one-size-fits-all recommendation can be made at present. In this sense, there must be a shared decision among the multidisciplinary team (interventional cardiology, cardio-oncology, and oncology team) and patients for the sake of a more personalized approach [44].

Limitations

This study has limitations. First, our prognostic research question limited inclusion to observational studies, which may have introduced selection bias and confounders to our analysis. We addressed this limitation by performing sensitivity analysis adjusted for confounders for the outcome of mortality, as available in the individual studies, and found consistent results. Second, as a study-level meta-analysis, we were unable to perform subgroup or meta-regression analyses based on cancer type, and device used due to incomplete reporting and limited number of included studies. Third, two studies may have included non-melanoma skin cancers, which are indolent tumors with a less malignant behavior. Nonetheless, they accounted for only six out of 9,792 cancer cases, having a much-limited impact on the overall cohort. Finally, we included registries with data from patients across the spectrum of surgical risk, which could not be addressed in full in a study-level meta-analysis. While this might have made our results less generalizable, we performed adjusted analyses using variables considered by the standard surgical risk calculators, yielding consistent results. We believe that our findings at least reflect the real-world setting. Future studies are warranted to determine the role of and optimal timing for TAVR in this population.

Conclusion

In this meta-analysis of observational studies, patients with active cancer undergoing TAVR had higher non-cardiovascular mortality and bleeding rates, with comparable incidences of other complications. Since the higher mortality may be driven by the underlying malignancy, the procedure itself may be safe if there is an appropriate patient selection. This highlights the need for a shared decision considering cancer type, staging, bleeding risk, and optimal timing for intervention.

Fig. 1 Forest plots for mortality endpoints. Legend: Patients with active cancer had significantly higher short- (A) and long-term (B) mortality rates as compared with patients without cancer. CI: confidence interval; OR: odds ratio

Fig. 2 Forest plot for cardiovascular mortality. Legend: Patients with active cancer had cardiovascular mortality rates comparable to those without cancer after transcatheter aortic valve replacement. CI: confidence interval; OR: odds ratio

Fig. 3 Analyses with adjustment for confounding factors. Legend: (A) Patients with active cancer had a significantly higher all-cause mortality rates even after adjustment for confounders; (B) patients with advanced stage malignancies had even higher mortality rates. CI: confidence interval; HR: hazard ratio; SE: standard error

Fig. 4 Forest plot for major bleeding. Legend: Patients with active cancer had a higher incidence of major bleeding after transcatheter aortic valve replacement relative to patients without cancer. CI: confidence interval; OR: odds ratio

Table 1 Study characteristics

Characteristics	Aikawa, 2023
(N = 122,573)	Biancari, 2020
(N = 1,826) b	Kojima, 2022
(N = 1,114)	Landes, 2019
(N = 2,744)	Lind, 2020
(N = 892)	Mangner, 2017
(N = 1,570)	Tabata, 2020
(N = 1,568) b	Trimaille, 2023
(N = 1,125)	Watanabe, 2016
(N = 749)	
AC
(n = 8,013)	No AC
(n = 114,560)	Cancer
(n = 417)	No cancer
(n = 1,713)	AC
(n = 62)	No AC
(n = 1,052)	AC
(n = 222)	No AC
(n = 2,522)	AC
(n = 53)	No AC
(n = 839)	AC
(n = 99)	No AC
(n = 1,471)	Cancer
(n = 298)	No Cancer
(n = 1,270)	AC
(n = 88)	No AC
(n = 1,037)	AC
(n = 47)	No AC
(n = 702)	
Study design	Retrospective cohort	Retrospective cohort	Retrospective cohort	Retrospective cohort	Retrospective cohort	Prospective cohort	Retrospective cohort	Prospective cohort	Prospective cohort	
Country	United States of America	Finland	Japan	Multinational	Germany	Germany	Germany	France	Japan	
Study duration	2012–2019	2008–2017	2010–2019	2008–2016	2006–2018	2006–2014	2008–2018	2010–2019	2013–2015	
Follow-up duration	6 months	2.1 years d	1.6 years d	330 days d	10 years	3 years e	5 years	2 years	272 days d	
Age, years a	79.6	79.6	80.6	81.4	83.0	85.0	78.8	81.3	78.5	81.4	81.0	81.0	80.8	81.1	80.9	83.0	83.0	85.0	
Female, %	41.1	46.8	51.1	56.0	60.0	69.1	37.8	55.0	54.7	54.5	40.4	57.3	39.9	53.2	46.6	55.0	55.3	67.0	
Diabetes mellitus, %	34.9	38.4	22.8	29.8	32.3	22.7	27.9	36.0	32.0	34.6	38.4	43.6	25.0	28.7	28.4	32.1	29.8	24.9	
Hypertension, %	84.2	87.9	NA	NA	67.7	78.2	76.1	92.0	96.2	94.7	93.9	93.6	NA	NA	77.3	83.3	74.5	75.6	
CAD, %	66.7	70.0	29.5	29.8	NA	NA	NA	NA	54.7 c	63.6 c	52.0	53.1	61.3	62.4	47.7	47.7	25.5	24.2	
Atrial fibrillation, %	40.6	40.0	43.4	43.8	NA	NA	NA	NA	13.2	21.8	NA	NA	46.9	41.7	42.0	45.7	17.0	19.1	
STS score, points a	NA	NA	4.4	4.6	5.2	5.8	4.9	6.2	5.4	6.0	6.0	6.7	5.4	5.4	6.9	6.5	5.4	7.0	
EuroSCORE II, points a	NA	NA	NA	NA	3.9	4.3	4.2	5.4	NA	NA	NA	NA	6.2	6.8	4.5	6.0	3.1	3.9	
LVEF, %*	NA	NA	NA	NA	63.0	63.0	56.0	56 0.0	48.8	51.3	57.0	58.0	53.9	54.2	54.0	53.0	65.9	65.0	
mAVPG, mm Hg a	NA	NA	NA	NA	51.0	48.0	49.0	48.0	NA	NA	44.0	42.0	NA	NA	50.0	47.0	50.4	48.0	
AVA, cm² a	NA	NA	NA	NA	0.7	0.7	0.7	0.6	0.6	0.7	0.7	0.7	NA	NA	0.7	0.7	0.6	0.6	
a Mean or median. b Did not display data for the subgroup of patients with active cancer. c Recent myocardial infarction. d Average follow-up, mean or median. e The maximum follow-up was 13 years; however, we collected the data as the 10-year mortality outcome

AC: active cancer; CAD: coronary artery disease; EuroSCORE: European System for Cardiac Operative Risk Evaluation; STS: Society of Thoracic Surgeons; LVEF: left ventricular ejection fraction; mAVPG: mean aortic valve pressure gradient; AVA: aortic valve area

The STS and EuroSCORE calculators assess risk of operative morbidity and mortality after adult cardiac surgery (TAVR) accounting for the planned procedure, demographics, laboratory values, preoperative medication use, risk factors/comorbidities, and cardiovascular disease (coronary artery disease, valvular heart disease, and arrhythmia)

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Abbreviations

aHR Adjusted hazard ratio

AKI Acute kidney injury

CI Confidence interval

MD Mean difference

OR Odds ratio

PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO International Prospective Register of Systematic Reviews

QUIPS Quality in Prognosis Studies

VARC Valve Academic Research Consortium

TAVR Transcatheter aortic valve replacement

Acknowledgements

Not applicable.

Author contributions

N.F. conceived and designed the study. N.F. and A.N. independently assessed the studies for possible inclusion. N.F., A.N., and P.E.P.C. collected the data. N.F. and A.N. analyzed the data. N.F., A.N., P.E.P.C., and T.A.C. produced the first draft of the manuscript. N.F., L.T., G.G., P.G., S.F., and M.C.A.D.F. interpreted the data and contributed to the writing of the final version of the manuscript. All authors critically revised and edited the final version of the manuscript for intellectual content. All authors agreed with the results and conclusions of this article.

Funding

No funding was received for conducting this study.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Conflicts of interest

Authors report no relationships that could be construed as conflicts of interest to this manuscript. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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