Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy

Abstract

We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.

Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy

“…However, Briguori et al 18 reported that plasma concentration of ANP in HCM was strongly associated with left atrial function, whereas BNP was strongly associated with obstruction. Only one study, including only 40 patients, has investigated MR-proANP in patients with HCM, showing that among several biomarkers, MR-proANP was the only one associated with the extent of late gadolinium enhancement on MRI 26. As previous studies, we found a significant association between NYHA and natriuretic peptides although there was a significant overlap between NYHA 2 and 3–4 (figure 1).…”

Biomarkers in patients with myocardial fibrosis

“…The specificity, positive and negative predictive value were satisfying. The results imply that MR-proANP is a potential biomarker of myocardial fibrosis in patients with HCM [63].…”

Higher copeptin levels are associated with worse outcome in patients with hypertrophic cardiomyopathy

“…A recent metaanalysis has shown that measurement of copeptin levels in addition to Tn improves the sensitivity and negative likelihood ratio for diagnosis of acute MI compared with Tn alone. 29 33 They did not find a relation between copeptin levels and degree of cardiac fibrosis in HCM. They found that LV and LA diameters and IVS thickness were higher in patients with cardiac fibrosis, but they did not classify patients as obstructive and nonobstructive HCM.…”

“…They found that copeptin levels increased significantly 30 minutes after induction of MI and peaked at 90 minutes. Elmas et al assessed the correlation of various biochemical parameters, including copeptin, with cardiac fibrosis detected by magnetic resonance imaging in 40 patients with HCM . They did not find a relation between copeptin levels and degree of cardiac fibrosis in HCM.…”