Cardiovascular disease and cancer are the leading causes of morbidity and mortality in high-income countries.1 These 2 conditions have a bidirectional relationship and share risk factors and underlying mechanisms.2 Continuous advances in medical care leading to higher survival rates for both diseases, together with population aging, have increased the overlap between cardiovascular disease and cancer.3,4 Traditionally, cardio-oncology has focused primarily on left ventricular systolic dysfunction; however, this perspective has recently broadened to include other cardiac toxicities such as coronary heart disease, arrhythmias, and valvular heart disease.5–7

Mitral regurgitation (MR) is the second most common form of valvular heart disease in the general population.8 Accordingly, MR may co-occur in cancer survivors as an incidental overlap given the high prevalence of both conditions. In addition, patients with a history of cancer have increased risks of degenerative MR (DMR) and functional MR (FMR) due to radiation therapy and anticancer drug exposure, respectively.9,10 Regardless of the nature of MR, the choice of the best treatment in this context is often challenging because of the relative frequency of comorbidities, frailty, poor functional status and prior surgical procedures in these patients. Mitral transcatheter edge-to-edge repair (M-TEER) is a feasible and less invasive alternative to surgery for MR, and its use in high surgical risk patients is supported by randomized clinical trials and recommended by the most recent international guidelines.8,11

In this nationwide study, we evaluated periprocedural, clinical, echocardiographic and functional outcomes in a cohort of patients with a prior cancer diagnosis who underwent M-TEER.

In this multicenter cohort of patients undergoing M-TEER in Spain, the main findings were as follows: a) the proportion of patients with a prior cancer diagnosis was noteworthy and increased over time; b) MR etiology was associated with tumor location and cardiotoxic treatment regimens, although in most patients it was not directly attributable to cancer-related therapies; c) a history of malignancy was not associated with worse clinical outcomes compared with matched controls, although patients with hematologic malignancies had a less favorable prognosis; and d) a prior cancer diagnosis did not influence echocardiographic or functional status at 1-year of follow-up.

Since the regulatory approval of M-TEER more than a decade ago, its adoption in clinical practice has expanded significantly. In parallel, the burden of comorbidities among patients undergoing this procedure has also increased.18,19 In our study, 13.3% of patients undergoing M-TEER had a history of malignancy, a prevalence that agrees with prior reports ranging from 3.4% to 22.5%.20–26 Furthermore, we observed an increasing trend in the proportion of M-TEER procedures performed in patients with a history of cancer, consistent with findings reported by Guha et al.22 Given this increasing trend and the lack of data from landmark M-TEER randomized controlled trials for this subgroup, insights from this study may help guide shared decision-making in routine practice, particularly when the risk-benefit balance of the procedure remains unclear.27,28

Our results provide further insight into the characterization of MR in patients with a history of cancer, an aspect that has been underexplored, likely due to the administrative nature of databases or the single-center design of prior investigations. Among these, only 3 single-center studies detailed the etiology of MR, with FMR being the most frequent in 2 of them, a finding consistent with our observations.24–26 To our knowledge, this is the first study to describe an association between cancer type, treatment combinations, and MR type. We found that FMR was present in 75% of leukemia/lymphoma patients, while DMR was observed in 60% of lung cancer survivors. These associations may be attributable to the high prevalence of anthracycline exposure and left-sided chest radiotherapy, respectively, which were associated with FMR and DMR, respectively.

One of the key clinical questions when evaluating MR in cancer survivors is whether its etiology is directly related to cancer therapies (eg, DMR following left-sided or mediastinal radiotherapy) or indirectly related (eg, FMR in the context of anthracycline or anti-HER2 therapy-related cardiac dysfunction), or whether it simply reflects incidental coexistence due to the high prevalence of both conditions, particularly in survivors of extrathoracic malignancies not exposed to systemic treatments (eg, localized prostate or colorectal cancer). In our cohort, approximately one third of patients had MR that appeared to be related to prior oncologic therapy, while in the majority, the coexistence of cancer and MR lacked a clear causal link.9,10,29–32 A second question is whether the consideration of M-TEER should depend on the cardiotoxic etiology of MR. We found no significant prognostic differences between these 2 subgroups, suggesting that M-TEER may be an appropriate therapeutic option for cancer survivors regardless of MR etiology. However, decisions should be individualized, considering the characteristics of MR and the overall clinical profile of each patient.

Cancer survivors are at increased risk of frailty, poor functional status, and other conditions that may shift shared decision-making for MR treatment toward a noninterventional approach.33 Despite these concerns, prior studies consistently indicate that M-TEER is a feasible and safe alternative in these patients, with periprocedural outcomes and 30-day mortality rates comparable to those of noncancer counterparts.20–24 Only a single-center study suggested a trend toward increased mortality compared with controls.26 However, this finding should be interpreted with caution due to the small sample size and potential residual confounding, as the included cancer survivors had higher EuroSCORE II values than controls (14.0 ± 11.4 10.0 ± 6.7; P = .01). Our findings concur with the prevailing consensus that patients with a history of malignancy do not present an excess 30-day mortality risk compared with those without prior cancer.20–24

With respect to longer-term clinical outcomes, prior literature is inconclusive. On the one hand, Khan et al.,23 using electronic health records from the TriNetX Platform, and Kalkan et al.,24 in a single-center study of 143 patients with history of cancer, found no difference in 1-year all-cause mortality compared with controls., On the other hand, smaller single-center studies reported increased 1-year mortality in cancer survivors.25,26 Our multicenter study appears to shift the balance toward the former, showing no significant differences in mortality or heart failure hospitalizations at 1 year. Importantly, the neutral impact of a prior cancer diagnosis on clinical endpoints was supported by secondary endpoints, which showed comparable improvements in functional class and residual MR grade between groups. However, our findings should be interpreted with caution, as they are based on a selected cohort of cancer survivors from routine clinical practice, characterized by a long median time since cancer diagnosis, a substantial proportion without exposure to anthracyclines or chest radiotherapy, and a lower average EuroSCORE II compared with other series. In addition, our multivariable analysis identified subgroups with a less favorable prognosis. In particular, survivors of hematologic malignancies had a 2-fold increased risk of the primary endpoint (adjusted HR, 2.02; 95%CI, 1.15–3.55; P=.015), consistent with findings from the CARDIOTOX registry, where these malignancies were associated with worse outcomes related to cancer therapy-induced cardiac dysfunction due to high cumulative doses of anthracyclines.34 Although the association in our study appeared independent of anthracycline exposure, it is important to note that most of these patients did receive anthracyclines, and we lacked data on cumulative dose, which may have limited our ability to detect a dose-response relationship. Lastly, patients with hematologic malignancies did not have higher EuroSCORE II values than those with solid tumors. Moreover, anthracycline-treated patients showed slightly lower EuroSCORE II values, and no significant interaction was found between EuroSCORE II and anthracycline exposure. These findings suggest that the increased risk observed in hematologic malignancies (and the lack of prognostic impact of anthracycline exposure) cannot be explained by differences in baseline surgical risk.

In this nationwide multicenter study of M-TEER patients, a prior cancer diagnosis did not negatively impact all-cause mortality or heart failure hospitalizations at midterm follow-up. Furthermore, echocardiographic and functional assessments at 1 year were comparable with those of patients without prior malignancy. However, certain subgroups, particularly survivors of hematologic malignancies and those with higher baseline surgical risk, had a less favorable prognosis.

R. González-Manzanares was awarded research contracts (CM22/00259, JR24/00064) and an international mobility grant (MV24/00106) from the Carlos III Health Institute (Madrid, Spain). Funding for open access charge: Universidad de Córdoba / CBUA.

The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Córdoba, Spain (code 5956). Owing to the observational design based on pseudonymized routinely collected data, the requirement for written informed consent was waived. Regarding potential sex/gender bias, we followed the SAGER recommendations where feasible: sex was recorded, reported in baseline characteristics, and included in propensity score models; sex-stratified analyses were not performed due to limited sample size. The current work follows the STROBE (Strengthening the Reporting of Observational studies in Epidemiology) guidelines for reporting observational studies

This work was prepared by the authors without the use of artificial intelligence.

R. González-Manzanares: conceptualization, methodology, formal analysis, visualization, writing–original draft, writing–review and editing. S. Ojeda: conceptualization, investigation, supervision, project administration, writing–review and editing. D. Mesa: conceptualization, investigation, supervision, project administration, writing–review and editing. M. Pan: conceptualization, investigation, supervision, project administration, writing–review and editing. All other authors contributed to the investigation process and reviewed and provided conceptual feedback. All authors approved the final version of the manuscript.

S. Ojeda has received consulting honoraria from Abbott and speaker honoraria from Edwards Lifesciences. F. Carrasco-Chinchilla has received proctoring honoraria from Abbott and Edwards Lifesciences for M-TEER procedural imaging. L. Nombela-Franco has received proctoring honoraria from Abbott and Edwards Lifesciences. R. Estévez-Loureiro has received consulting and speaker fees from Abbott, Edwards Lifesciences, Boston Scientific, Venus Medtech, Jenscare, and Valgen. M. del Trigo has received proctoring honoraria from Abbott for M-TEER procedures and speaker fees from Abbott and Edwards Lifesciences. X. Freixa has received proctoring and consulting honoraria from Abbott and Edwards Lifesciences. I. Cruz-González has received proctoring and consulting honoraria from Abbott and consulting honoraria from Edwards Lifesciences. C. Garrote-Coloma has received proctoring honoraria from Abbott for M-TEER procedures. P. Jiménez Quevedo has received proctoring honoraria from Abbott for M-TEER procedures. V. Moñivas has received proctoring honoraria from Abbott for M-TEER procedures and speaker fees from Abbott and Edwards Lifesciences. A. Ruberti has received a training grant from Edwards Lifesciences. M. Pan has received speaker honoraria from Abbott and Edwards Lifesciences. All other authors have no relationships to disclose. J. Sanchis is editor-in-chief of Revista Española de Cardiología and P. Avanzas is associate editor of Revista Española de Cardiología; the journal's editorial procedure to ensure impartial processing of the manuscript has been followed.