Why the study?
Human epididymis protein 4 identifies fibrosis, but its relationship with other blood biomarkers and myocardial fibrosis by CMR in patients undergoing TAVI is not well established.
Do elevated plasma levels of HE4 and CA-125 correlate with diffuse myocardial fibrosis assessed by CMR in patients with severe aortic stenosis undergoing TAVI?
Do elevated plasma levels of HE4 and CA-125 correlate with diffuse myocardial fibrosis assessed by CMR in patients with severe aortic stenosis undergoing TAVI?
Elevated HE4 and CA-125 plasma levels are promising blood biomarkers that correlate with CMR-detected diffuse myocardial fibrosis in patients with severe aortic stenosis.
Answers are grounded in this paper and cite their sources.
May support HE4/CA-125 as fibrosis markers in severe AS; hypothesis-generating, needs prospective validation before adoption.
Introduction: Cardiovascular magnetic resonance (CMR) T1 mapping, extracellular volume (ECV) and late gadolinium enhancement (LGE) demonstrate strong agreement with endomyocardial biopsy in evaluating myocardial fibrosis. Human epididymis protein 4(HE4) has been shown as a blood biomarker to identify fibrosis, but the relationship with other blood biomarkers is not well established yet. Hypothesis: determine the correlation between different blood biomarkers and myocardial fibrosis by CMR in patients undergoing transcatheter aortic valve implantation(TAVI). Methods: Forty-three patients were included. The cohort was divided into two groups based on the threshold values of HE4(128.5 pmol/l) and/or CA-125 (19.5 U/ml), before TAVI. Native T1 mapping and ECV were measured at 1280 ms and 26%, respectively, corresponding to the median of the population studied. LGE was qualitatively measured. Results: Patients with higher HE4 plasma levels (> 128.25 pmol/l) and/or CA-125 (>19.5 U/ml) prior to TAVI had more comorbidities and had higher median native T1 mapping values, 1278 ms (1239.25-1280.25) vs 1352 ms (1303.50 -1376.00), p < 0.001, and LGE positive, 10 (55.6%) vs 10 (90.9%); p= 0.046, respectively. HE4 (r=0.34, p=0.03) and CA-125 (r=0.371, p=0.034) correlated with prolonged T1 mapping. No significant correlation was found with other biomarkers: troponin T (r = 0.14, p = 0.41), Nt-proBNP (r=0.28, p=0.089), IL-6 (r=0.189, p= 0.250), procalcitonin, (r =0.132, p =0.420). The addition of elevated plasma levels of HE4 and CA-125, provided significant C-statistics for myocardial fibrosis, AUC [95%CI]: 0.74 [0.58- 0.89], p= 0.008, regarding HE4 AUC [95%CI]: 0.69 [0.52- 0.85], p=0.039, and CA-125 AUC [95%CI]: 0.72 [0.57- 0.88], p= 0.014. On univariable analysis, high plasma levels of HE4 and/or Ca-125 were independently associated with diffuse fibrosis by native T1 mapping OR:9.37, [95% CI: 2.07 - 42.33], p = 0.004 and there was a trend toward focal fibrosis by LGE + OR: 8.00, [95% CI: 0.83 - 76.36], p = 0.071. Conclusion: Elevated HE4 and/or Ca-125 plasma levels correlated with prolonged native T1 mapping. The combination of HE4 values ≥ 128 pmol/l and CA-125 ≥ 19.5 U/ml may provide a useful screening biomarker to identify diffuse myocardial fibrosis in AS.
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Zanuttini et al. (2023) studied this question.
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