Ahmed Bendary describes the findings of a meta-analysis published last month that determined outcomes for cancer patients following transcatheter aortic valve implantation (TAVI). He tells Cardiovascular News what can be done to ensure that these patients survive valvular problems.
Patients with coexisting severe aortic stenosis and active cancer are considered to be a high-risk group and are usually not offered surgical valve replacement due to concerns over a higher likelihood of postoperative complications and because cancer therapeutics would need to be withheld perioperatively. TAVI may be an attractive option that could allow them correction of their valvular problem at lower operative risk, as well as easing their access to oncological surgeries, otherwise contraindicated in uncorrected severe aortic stenosis. However, patients with cancer have been largely excluded from pivotal TAVI trials, because from an ethical point of view it is difficult to randomise them between various treatment options. This leaves little evidence to guide clinical decision-making.
In a meta-analysis published online in March in OpenHeart-BMJ, our group searched Medline, Cochrane Library, and Scopus databases (anytime up to April 2019) for studies evaluating the outcomes of TAVI in patients with or without active cancer. We assessed pooled estimates (with their 95% confidence intervals [CIs]) of the risk ratio (RR) for all-cause mortality at 30-day and 1-year follow-up, a four-point safety outcome (any bleeding, stroke, need for a pacemaker, and acute kidney injury) and a two-point efficacy outcome (device success and residual mean gradient [mean difference]). Three studies (5,162 patients) were included. Of those patients, a total of 368 (7.1%) had active cancer. The most common types of cancer were gastrointestinal (22.6%), prostate (18.4%), haematological (17.1%), and female breast (14.4%).
Stage of cancer is important
Overall, 30-day all-cause mortality did not differ significantly between patients with and without active cancer (RR 0.92, 95% CI 0.53–1.59). But all-cause mortality at one-year follow-up was 71% higher among patients with active cancer than among those without cancer (RR 1.71, 95% CI 1.26–2.33). Importantly, these findings differed by cancer stage. However, we also found that rates of all-cause mortality at both 30 days and one year were similar among patients without cancer and those with limited cancer stages. In contrast, patients with advanced cancer stages had similar all-cause mortality at 30 days (RR 1.32, 95% CI 0.67–2.59), but significantly higher rates of all-cause mortality at one year when compared to patients without cancer. All-cause mortality at one year was 2.33-fold higher in patients with advanced cancer than in patients with limited cancer. Of note, advanced cancer was defined as a stage greater than T2 for the primary tumour, and/or N1 for lymph nodes, and/or M1 for metastases, as well as any malignancy considered refractory, relapsing, or recurrent.
The rates of device success did not differ significantly between the patient groups, and there were no significant differences in 30-day rates of bleeding, stroke, or acute kidney injury. The only safety outcome that was higher in the cancer group compared with the non-cancer group was need for a pacemaker (RR 1.29, 95% CI 1.06–1.58, p=0.01).
Pacemaker implantations high
The significantly higher need for a postprocedural pacemaker in patients with cancer in the current study might be explained by the well-known arrhythmogenic impact of various antineoplastic therapies (for example, methotrexate, 5-fluorouracil and cisplatin), putting patients with cancer at a higher risk for such a complication, by making their cardiac conductive tissue more vulnerable to any mechanical injury imposed by the TAVI procedure.
Current guidelines do not recommend TAVI in patients whose life expectancy is less than one year. Here, our finding that one-year all-cause mortality seems to be dependent on cancer stage is noteworthy, but needs to be interpreted with caution considering the observational nature of the included studies (with the inherent bias introduced by confounders), and the heterogeneity of the examined population (many cancer types with variable therapies, prognoses, and so on). Moreover, predicting life expectancy in patients with cancer is usually difficult, and cancer itself is not reflected in the conventional preoperative the Society of Thoracic Surgeons (STS) risk score. At one-year follow-up, mortality in patients with cancer across the included studies were mainly non-cardiovascular. Therefore, involving a specialised oncologist who usually considers cancer stage in the decision-making might refine the risk assessment process to help exclude those patients with cancer in whom TAVI would really be futile.
The significance of this meta-analysis is two-fold. To the best of our knowledge, this is the first systematic review and meta-analysis in the literature addressing this clinical question. It reaffirms the findings of individual studies, with a higher degree of evidence and statistical power, giving clinicians a chance to make better-informed decisions. Moreover, our pooled estimates (with the little heterogeneity observed across studies) came from different ethnic groups and many different operators with different practising patterns. This implies that any findings may be extrapolatable to a broad spectrum of patients.
Cardio-oncology is applicable to anyone, anytime. Accordingly, the collaboration between cardiologists and oncologists is indispensable. Our findings that many patients with severe AS and active cancer appear to benefit from TAVI, with mortality rates, safety, and efficacy outcomes similar to those for patients without cancer, should set the stage for TAVI as an acceptable option for them. It is bitter to imagine that cancer patients might succumb to their valvular problem rather than cancer itself.
Ahmed Bendary is at the cardiology department in the Benha Faculty of Medicine at Benha University, Egypt
Bendary A, Ramzy A, Bendary M, Salem M. Transcatheter aortic valve replacement in patients with severe aortic stenosis and active cancer: a systematic review and meta-analysis. Open Heart BMJ 2020; 7: e001131.