Biomarkers and Outcomes in Patients Undergoing Surgical AVR

Study Questions:

Is a combination of elevated biomarkers of cardiovascular risk associated with worse outcomes in patients with severe aortic stenosis?

Methods:

High-sensitivity troponin T, human epididymis protein 4, cancer antigen 125, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide were measured in 665 patients with severe aortic stenosis who underwent surgical aortic valve replacement (AVR) and enrolled in a biobank registry. Outcomes including all-cause death, cardiovascular death, and rehospitalization were examined over a median follow-up time of 10.7 years. Survival analysis was performed for each biomarker separately, then with the number of elevated biomarkers using the median across the cohort as the cutoff.

Results:

Overall, the cohort consisted of 44% women, with a median age of 70 years, and a mean left ventricular ejection fraction of 60%, with 46% of patients having New York Heart Association class III or IV symptoms. Elevated levels of each individual biomarker were associated with increased risk of death, with the highest hazards for mortality seen with higher levels of high-sensitivity troponin T, human epididymis protein 4, and growth differentiation factor 15. When combined, for each biomarker elevated, there was an approximate 20% increase in mortality across subgroups. The authors note that 42% of patients with ≥4 biomarkers and subsequently worse outcomes had minimal symptoms.

Conclusions:

An increasing number of elevated biomarkers of cardiovascular stress are associated with mortality and rehospitalization.

Perspective:

This study, like several others done in various populations, highlights the fact that circulating biomarkers can be used to risk stratify patients. While the authors state that the objective of the study was to identify a “biomarker trigger” for AVR—a worthwhile endeavor for the clinical implementation of biomarkers—neither the study design nor analysis allows for that, as the study was performed in patients who already had an indication for AVR. Whether biomarkers can be used to identify patients who do not meet current guideline criteria for AVR but may benefit remains to be seen.

Keywords: Aortic Valve Stenosis, Biomarkers, Cardiac Surgical Procedures, Growth Differentiation Factor 15, Heart Failure, Heart Valve Diseases, Heart Valve Prosthesis, Natriuretic Peptide, Brain, Neoplasms, Peptide Fragments, Risk Factors, Survival Analysis, Transcatheter Aortic Valve Replacement, Troponin T


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