Download this article's Factoid (PDF & PPT for Gold Subscribers) 

Elevated baseline levels of the biomarker carbohydrate antigen 125 (CA125) appear to predict adverse outcomes in patients who undergo transcatheter aortic valve replacement (TAVR), according to a single-center observational study published in the May 2013 issue of JACC: Cardiovascular Interventions. Additionally, serial measurement of postprocedural CA125 levels may help monitor patients’ changing prognoses.

Researchers led by Christian Hengstenberg, MD, of the Deutsches Herzzentrum München (Munich, Germany), measured CA125 in blood samples of 228 patients before and after TAVR and correlated the levels with clinical outcomes.

Established Cancer Marker Linked to Heart Failure

CA125, best known as a biomarker of ovarian cancer, is released by mesothelial cells in response to serosal effusions and/or proinflammatory cytokines. Recently it has emerged as a biomarker of heart failure as well.

TAVR was successfully performed in 221 patients (97%), with device success achieved in 86%. Procedural mortality was 2% and overall 30-day mortality was 7%. During a median follow-up of 183 days, 22% of patients died. MACE were seen in 33% over a median follow-up of 144 days; events included 42 deaths, 28 admissions for acute heart failure, 4 strokes, and 1 MI.

Median preprocedural CA125 was higher in patients who died (28 U/mL vs. 12 U/mL; P = 0.001) or experienced MACE (23 U/mL vs. 14 U/mL; P = 0.003) compared with those who did not.

In patients with elevated baseline CA125 levels, there was an approximate threefold increase in rates of death (5.2 vs. 1.6 per 10 person-years) and MACE (8.3 vs. 3.3 per 10 person-years; P < 0.001 for both).

In multivariate analysis adjusting for logistic EuroScore, NYHA functional class III/IV, and device success, baseline CA125 remained independently associated with increased risk of all-cause death (HR 2.18; 95% CI 1.11-4.26; P = 0.023) and MACE (HR 1.77; 95% CI 1.05-2.98; P = 0.031).

In a sensitivity analysis in which NT-proBNP was forced into the final model, the proposed prognostic marker was not associated with either all-cause death or MACE, while the link to CA125 remained almost unaltered for both endpoints.

Longitudinal CA125 Also Predictive 

After controlling for longitudinal NT-proBNP and baseline values of the logistic EuroScore, NYHA functional class III/IV, and device success, regression analysis identified longitudinal CA125 as a powerful independent predictor of both all-cause death (HR 1.47; 95% CI 1.01-2.14; P = 0.043) and MACE (HR 2.26; 95% CI 1.28-3.98; P = 0.005).

The authors observe that identifying patients who might benefit most from closer follow-up and/or monitoring after TAVR is challenging because even with a successful procedure, patients remain at high risk due to preexisting comorbidities. In this setting, biomarkers may be an appealing tool not only for assessing preprocedural risk but also for monitoring treatment success.

According to the investigators, CA125 provides certain advantages over other potential biomarkers. For example:

• Levels correlate closely with heart failure severity as well as increased risk of death and subsequent readmission for acute heart failure
• Testing is widely available and less expensive than other markers
• Plasma levels do not seem to be influenced by age, renal function, or BMI
• Changes in CA125 over time are more likely to be due to changes in disease status than to simple biological variation

New Marker Welcome, but Needs Confirmation

“Anything that can provide an objective measurement of the prognosis of these patients is welcome, and this is a promising marker,” Josep Rodés-Cabau, MD, of Laval University (Quebec City, Canada), told TCTMD in a telephone interview. “But with the small number of patients and the large number of confounders in the study, I’m not sure we can conclude much. We need more data.”

Adding to the uncertainty, he noted, CA125 is relatively new to the heart failure field, whereas NT-proBNP has been very well studied in heart failure and has even shown potential usefulness in several TAVR papers. Whether or not CA125 is superior remains to be proven, he added.

Postprocedural hemodynamic outcomes are very important, Dr. Rodés-Cabau observed, but the authors devoted little attention to how they might have affected CA125 levels. They also failed to explore the relative association of the marker with cardiac vs. noncardiac mortality, he noted, although that may not have been feasible due to the small number of total deaths.

The authors suggest that high preprocedural CA125 levels might prompt clinicians to optimize medical treatment before TAVR, while high postprocedural levels might spur closer follow-up, Dr. Rodés-Cabau observed. But “in the future [CA125] may be most helpful in generating a [TAVR] risk score,” he said.

Ideally, this tool would integrate several biomarkers and multiple well-established clinical prognostic factors such as frailty, COPD, and renal failure into an algorithm that would predict mortality, much like a surgical risk score. That way, he added, “we would have a [cut-off] number where we would be able to say to the patient, ‘Your overall risk of dying from the procedure is simply too high. There is no advantage to it.’” 

Study Details

TAVR was performed either via the transfemoral approach (n = 137) using a balloon-expandable (Sapien XT; Edwards Lifesciences, Irvine, CA; n =79) or self-expandable (CoreValve; Medtronic, Minneapolis, MN; n = 58) device, or by the transapical approach (n = 89) using Sapien XT. In addition, 1 procedure was performed via a subclavian approach and 1 by a direct aortic approach. 

Related Stories:

• Predictors of Aortic Regurgitation After TAVR Delineated
• Frailty Index Best at Predicting Functional Decline After TAVR
• TAVR Studies Tease Out Influences on Clinical Outcome