T1 mapping of the right ventricle in heart transplant recipients: how does it correlate with endomyocardial biopsy findings?
Authors: Sade L E , Colak A , Duzgun S A , Hazirolan T , Sezgin A , Ozdemir H , Eroglu S , Pirat B , Muderrisoglu H 
Published: October 2022

Abstract

Aim
Noninvasive detection of cardiac allograft rejection is highly desirable. We sought to assess how right ventricular (RV) T1 mapping correlates with endomyocardial biopsy findings.

Methods
All patients underwent right heart catheterization with biopsy and cardiac magnetic resonance (CMR) irrespective of symptoms, as part of the institutional registry protocol dedicated to heart transplant (HTx) recipients. CMR studies were performed using a 1.5 T scanner and analyses by using a commercially available software (CMR42, Circle CVI, Calgary, Canada). Endocardial and epicardial borders were drawn on end-systolic and end-diastolic phases for ventricular function analysis. For T1 measurements, region of interests located at the RV free-wall were drawn manually on midventricular short-axis slices avoiding blood pool and epicardial fat. Extracellular volume (ECV) was calculated as ECV = (1 − hematocrit) × (ΔR1 myocardium/ΔR blood), where R1 = 1/T1. Late gadolinium enhancement (LGE) images were also obtained using a phase-sensitive inversion recovery segmented gradient echo sequence. Hyperenhancement was assessed semi-quantitatively as segmental (2–3 cm) or diffuse (&gt;3 cm). Allograft rejection was determined based on the severity of inflammatory infiltrates and myocyte damage on pathological specimens according to the standardized International Society for Heart and Lung Transplantation (ISHLT) nomenclature.

Results
In all, 61 paired studies were evaluated. None of the patients had heart failure symptoms. We defined 3 subgroups: Group I; never rejected (n=23), group II; biopsy remarkable for rejection (n=19) and group III; history of past rejection(s) (n=19). RV volumes and ejection fraction (EF) did not differ between the groups. However, rejections were nicely mirrored by T1 time and particularly by ECV. Of note, T1 time and ECV improved but not completely normalized after resolution of rejection. Overall, T1 time (cut off 1060ms) and ECV (cut off 35%) were sensitive (84%, both) and had high negative predictive values (88% and 87%, respectively) but not specific (43% and 52% respectively) for discriminating rejection related subclinical RV damage. Their specificity slightly improved to 52 and 61% respectively, if patients with previous rejection were excluded (Figure 1). LGE did not discriminate rejection.

Conclusion
RV volumes and EF are insensitive to detect allograft rejection. Native T1 time and ECV of the RV, as a means of extracellular expansion, likely reflect interstitial fibrosis, oedema, and inflammation that are typical for, but not limited to allograft rejection. Hence, these parameters can help to exclude rejection but have limited standalone value for making the nonivasive diagnosis due to their low specificity. These results cannot be extrapolated to the left ventricle.

Funding Acknowledgement
Type of funding sources: Private hospital(s). Main funding source(s): University of Baskent