Detection and evaluation of myocardial fibrosis in Eisenmenger syndrome using cardiovascular magnetic resonance late gadolinium enhancement and T1 mapping

Abstract

Background: Myocardial fibrosis is a common pathophysiological process involved in many cardiovascular diseases. However, limited prior studies suggested no association between focal myocardial fibrosis detected by cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) and disease severity in Eisenmenger syndrome (ES). This study aimed to explore potential associations between myocardial fibrosis evaluated by the CMR LGE and T1 mapping and risk stratification profiles including exercise tolerance, serum biomarkers, hemodynamics, and right ventricular (RV) function in these patients.

Methods: Forty-five adults with ES and 30 healthy subjects were included. All subjects underwent a contrast-enhanced 3T CMR. Focal replacement fibrosis was visualized on LGE images. The locations of LGE were recorded. After excluding LGE in ventricular insertion point (VIP), ES patients were divided into myocardial LGE-positive (LGE⁺) and LGE-negative (LGE^-) subgroups. Regions of interest in the septal myocardium were manually contoured in the T1 mapping images to determine the diffuse myocardial fibrosis. The relationships between myocardial fibrosis and 6-min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), hematocrit, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), RV/left ventricular end-systolic volume (RV/LV ESV), RV ejection fraction (RVEF), and risk stratification were analyzed.

Results: Myocardial LGE (excluding VIP) was common in ES (16/45, 35.6%), and often located in the septum (12/45, 26.7%). The clinical characteristics, hemodynamics, CMR morphology and function, and extracellular volume fraction (ECV) were similar in the LGE⁺ and LGE^- groups (all P > 0.05). ECV was significantly higher in ES patients (28.6 ± 5.9% vs. 25.6 ± 2.2%, P < 0.05) and those with LGE^- ES (28.3 ± 5.9% vs. 25.6 ± 2.2%, P < 0.05) than healthy controls. We found significant correlations between ECV and log NT-pro BNP, hematocrit, mPAP, PVRI, RV/LV ESV, and RVEF (all P < 0.05), and correlations trends between ECV and 6MWT (P = 0.06) in ES patients. An ECV threshold of 29.0% performed well in differentiating patients with high-risk ES from those with intermediate or low risk (area under curve 0.857, P < 0.001).

Conclusions: Myocardial fibrosis is a common feature of ES. ECV may serve as an important imaging marker for ES disease severity.

Keywords: Cardiovascular magnetic resonance; Eisenmenger syndrome; Extracellular volume; Myocardial fibrosis; T1 mapping.

Fig. 1

Representative ROI contours on native T1 and extracellular volume fraction (ECV) mapping images of a normal control (a native T1 mapping; c ECV mapping) and a patient with Eisenmenger syndrome (ES) (b native T1 mapping; d ECV mapping). The orange solid contour line represents the septum. The red dotted contour represents the blood pool. ROI region of interest, ECV extracellular volume, ES Eisenmenger syndrome

Fig. 2

Representative examples of late gadolinium enhancement (LGE) images. a Inferior ventricular insertion points (VIP), white arrow) and right ventricular (RV) myocardium (white chevron); b Anterior/inferior VIP (white arrow), septum (orange arrow) and left ventricular (LV) myocardium (white chevron); c Anterior/inferior VIP (white arrow), LV papillary (orange chevron), and RV trabeculae (orange chevron). LGE late gadolinium enhancement, VIP ventricular insertion point, LV left ventricular, RV right ventricular

Fig. 3

Native T1 and ECV box plots for the LGE-positive, LGE-negative, and normal control groups. ECV extracellular volume, LGE late gadolinium enhancement

Fig. 4

Correlations of myocardial native T1 with biomarkers, RV afterload, and RV remodeling. NT-pro BNP N-terminal pro-brain natriuretic peptide, PAP pulmonary artery pressure, PVR pulmonary vascular resistance, RV right ventricular, LV left ventricular, ESV end-systolic volume

Fig. 5

Correlation of myocardial ECV with biomarkers, RV afterload, and RV remodeling. ECV extracellular volume, NT-pro BNP N-terminal pro-brain natriuretic peptide, PAP pulmonary artery pressure, PVR pulmonary vascular resistance, RV right ventricular, LV left ventricular, ESV end-systolic volume

Fig. 6

Native T1 and ECV in ES patients with various risk profiles. ECV extracellular volume, ES Eisenmenger syndrome

Fig. 7

Receiver operating characteristic curves for discriminating ES patients with a high-risk profile from those with low- and intermediate-risk profiles. ECV extracellular volume, ES Eisenmenger syndrome