Noninvasive Quantification of Diffuse Myocardial Fibrosis with Cardiovascular Magnetic Resonance T1 Mapping in Pediatric Primary Inherited Cardiomyopathy

Objectives: Focal myocardial fibrosis detected by late gadolinium enhancement imaging in association with adverse clinical outcome has been reported in children and adolescents with primary inherited cardiomyopathy (CM). However, little is known about the extent of diffuse myocardial fibrosis (DMF) and its clinical relevance in these patients. The aim of this study was to determine DMF reflected by extracellular volume (ECV) with cardiovascular magnetic resonance (CMR) T1 mapping and to assess its association with clinical parameters, ventricular function, exercise capacity and pro brain natriuretic peptide (proBNP) as a biomarker for heart failure in pediatric primary inherited CM.

Methods: Nineteen prospectively enrolled patients (mean age: 13.0 ± 3.9 years, 7 females) with CM (dilated CM (DCM), n = 4; hypertrophic CM (HCM), n = 6; left ventricular non-compaction CM (LVNC), n = 7; restrictive CM, n = 1; arrhythmogenic right ventricular CM, n = 1) were compared with 8 healthy controls (15.3 ± 4.7 years, 5 female). The study protocol included standardized CMR at 1.5 Tesla with modified Look-Locker Inversion recovery (MOLLI) T1 mapping, cardiopulmonary exercise testing (CPEX) and blood sampling. Circumferential and septal ECV were calculated in midventricular and basal short axis planes.

Results: Septal ECV was significantly higher in DCM than in controls (42.7 ± 4.3% vs. 26.7 ± 3.6%, p = 0.012). In the patient group, circumferential and septal ECV were associated with age at CMR (r = −0.75 and −0.82, p < 0.01, respectively) and body surface area (r = −0.76 and −0.80, p < 0.01, respectively). Strong correlations were observed between circumferential ECV and LV ejection fraction (EF), maximum oxygen consumption from CPEX and proBNP in DCM (r = −1.0, 1.0 and −1.0, p < 0.01, respectively), between circumferential ECV and LV EF and end-systolic volume in HCM (r = 0.90, p = 0.037, respectively), and between septal ECV and LV-stroke volume in LVNC (r = 0.90, p = 0.037).

Conclusion: In this study population, increased ECV was significantly related to younger age and smaller body size. Furthermore, our results point to an increase of DMF in association with indices of heart failure including reduced LV function, impaired exercise capacity and elevated levels of proBNP in young patients with DCM. Future long-term studies are necessary to analyze the potential of non-invasive ECV measurements in supporting risk stratification and guiding therapy in children and adolescents with primary inherited CM.