What is the clinical evidence from this study?

Study design: Observational. Population: Paediatric heart transplant recipients (n=44). Intervention: Cardiovascular magnetic resonance T1 mapping vs. Healthy controls / Histological validation. Primary outcome: Correlation between histological collagen volume fraction and septal native T1 time (r = 0.53, p=<0.05).

December 1, 2016Open Access

Histological validation of cardiovascular magnetic resonance T1 mapping markers of myocardial fibrosis in paediatric heart transplant recipients

Q: What are the key findings of this study?

Cardiovascular magnetic resonance-derived native T1 times and extracellular volume fraction moderately correlated with the histological degree of fibrosis on endomyocardial biopsy in pediatric heart transplant recipients.

Key Result

Cardiovascular magnetic resonance-derived native T1 times and extracellular volume fraction moderately correlated with the histological degree of fibrosis on endomyocardial biopsy in pediatric heart transplant recipients.

Study Design

Type

Observational (n=44)

Multicenter

Structured PICO

Do CMR-derived native T1 times and extracellular volume fraction correlate with histological myocardial fibrosis in pediatric heart transplant recipients?

Population

20 pediatric heart transplant (HTx) recipients (mean age 9.9 ± 6.2 years, 9 girls/11 boys) at a median of 1.3 years post-HTx, and 24 controls (mean age 13.9 ± 2.6 years, 12 girls/12 boys).

Intervention

Cardiovascular magnetic resonance (CMR) with native T1 mapping and extracellular volume fraction (ECV) measurement using a modified Look-Locker inversion recovery (MOLLI) sequence

Comparator

Histological collagen volume fraction (CVF) quantified from endomyocardial biopsy (EmBx) stained with picrosirius red, and a healthy control group for CMR parameters

Outcome

Correlation between CMR-derived native T1 times and ECV with the histological degree of collagen (CVF) on endomyocardial biopsysurrogate

CMR-derived native T1 mapping and extracellular volume fraction correlate moderately with histological fibrosis on biopsy, suggesting they can serve as non-invasive markers for myocardial fibrotic remodeling in pediatric heart transplant recipients.

Main Result

Effect estimate: r = 0.53

p-value: p=<0.05

Limitations

Modest sample size may have obscured further differences and associations.
T1 and ECV were measured on a single short axis slice, which may not be representative of the entire left ventricular myocardium.
Differences in T1 and ECV between patients and controls could potentially be amplified by lower hematocrit levels in transplant recipients.
Coronary angiography was not available in close proximity to CMR and biopsy, preventing investigation of coronary allograft vasculopathy.

Abstract

BACKGROUND: Adverse fibrotic remodeling is detrimental to myocardial health and a reliable method for monitoring the development of fibrotic remodeling may be desirable during the follow-up of patients after heart transplantation (HTx). Quantification of diffuse myocardial fibrosis with cardiovascular magnetic resonance (CMR) has been increasingly applied and validated histologically in adult patients with heart disease. However, comparisons of CMR findings with histological fibrosis burden in children are lacking. This study aimed to compare native T1 times and extracellular volume fraction (ECV) derived from CMR with the degree of collagen on endomyocardial biopsy (EmBx), and to investigate the association between myocardial fibrosis and clinical as well as functional markers in children after HTx. METHODS: EmBx and CMR were performed on the same day. All specimens were stained with picrosirius red. The collagen volume fraction (CVF) was calculated as ratio of stained collagen area to total myocardial area on EmBx. Native T1 values and ECV were measured by CMR on a mid-ventricular short axis slice, using a modified look-locker inversion recovery approach. RESULTS: Twenty patients (9.9 ± 6.2 years of age; 9 girls) after HTx were prospectively enrolled, at a median of 1.3 years (0.02-12.6 years) post HTx, and compared to 24 controls (13.9 ± 2.6 years of age; 12 girls). The mean histological CVF was 10.0 ± 3.4%. Septal native T1 times and ECV were higher in HTx patients compared to controls (1008 ± 32 ms vs 979 ± 24 ms, p < 0.005 and 0.30 ± 0.03 vs 0.22 ± 0.03, p < 0.0001, respectively). CVF showed a moderate correlation with native T1 (r = 0.53, p < 0.05) as well as ECV (r = 0.46, p < 0.05). Native T1 time, but not ECV and CVF, correlated with ischemia time (r = 0.46, p < 0.05). CONCLUSIONS: CMR-derived fibrosis markers correlate with histological degree of fibrosis on EmBx in children after HTx. Further, native T1 times are associated with longer ischemia times.

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