Predictive values of multiple non-invasive markers for myocardial fibrosis in hypertrophic cardiomyopathy patients with preserved ejection fraction

Abstract

Myocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiac-specific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. The LGE-positive patients had significant higher serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels and lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group. The LGE% was independently associated with the Nt-proBNP levels, GCS, LV end-diastolic maximum wall thickness (MWT) and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP ≥ 108.00 pg/mL and MWT ≥ 17.30 mm had good diagnostic performance for LGE, with a specificity of 81.25% and sensitivity of 70.00%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.

Figure 1

Comparison of the mean serum hs-cTnI (a) and Nt-proBNP (b) levels between LGE-positive and LGE-negative patients. Correlations between the LGE% and the MWT (c), Nt-proBNP (d), GCS (e) and beta-blocker treatment (f) in HCM patients. hs-cTnI high-sensitivity cardiac troponin I, Nt-proBNP N-terminal pro B-type natriuretic peptide, LGE late gadolinium enhancement, MWT maximum wall thickness, GCS global circumferential strain.

Figure 2

ROC curve analysis of the serum Nt-proBNP levels (a), MWT (b) and the serum Nt-proBNP level + MWT (c) for the identification of the presence of LGE in HCM patients. AUC area under curve, ROC receiver operating characteristic curve analysis, LGE late gadolinium enhancement, HCM hypertrophic cardiomyopathy, MWT Maximum wall thickness, Nt-proBNP N-terminal pro B-type natriuretic peptide.

Figure 3

Example of left ventricular myocardium peak systolic strain analysis in a healthy volunteer. The left shows the colored tissue-tracking maps of longitudinal (a), circumferential (b), and radial (c) strain. In the middle is the 16-segment model of the longitudinal (d), circumferential (e), and radial (f) values in a cardiac cycle. On the right are the strain–time curves of the longitudinal (g), circumferential (h), and radial (i) values in a cardiac cycle.

Figure 4

Examples of hypertrophic cardiomyopathy patients with and without LGE. On the left are the short-axis cine (a) and LGE images (b) in a 46-year-old man. (c) Same image showing quantification of LGE using the 6SD thresholding method. (d) A representative 16-segment model of the LGE% in this patient. On the right are the short-axis cine (e) and LGE images (f) in a 46-year-old man without LGE. LGE late gadolinium enhancement.