Defining myocardial fibrosis in haemodialysis patients with non-contrast cardiac magnetic resonance

Abstract

Background: Extent of myocardial fibrosis (MF) determined using late gadolinium enhanced (LGE) predicts outcomes, but gadolinium is contraindicated in advanced renal disease. We assessed the ability of native T1-mapping to identify and quantify MF in aortic stenosis patients (AS) as a model for use in haemodialysis patients.

Methods: We compared the ability to identify areas of replacement-MF using native T1-mapping to LGE in 25 AS patients at 3 T. We assessed agreement between extent of MF defined by LGE full-width-half-maximum (FWHM) and the LGE 3-standard-deviations (3SD) in AS patients and nine T1 thresholding-techniques, with thresholds set 2-to-9 standard-deviations above normal-range (1083 ± 33 ms). A further technique was tested that set an individual T1-threshold for each patient (T11SD). The technique that agreed most strongly with FWHM or 3SD in AS patients was used to compare extent of MF between AS (n = 25) and haemodialysis patients (n = 25).

Results: Twenty-six areas of enhancement were identified on LGE images, with 25 corresponding areas of discretely increased native T1 signal identified on T1 maps. Global T1 was higher in haemodialysis than AS patients (1279 ms ± 5.8 vs 1143 ms ± 12.49, P < 0.01). No signal-threshold technique derived from standard-deviations above normal-range associated with FWHM or 3SD. T11SD correlated with FWHM in AS patients (r = 0.55) with moderate agreement (ICC = 0.64), (but not with 3SD). Extent of MF defined by T11SD was higher in haemodialysis vs AS patients (21.92% ± 1 vs 18.24% ± 1.4, P = 0.038), as was T1 in regions-of-interest defined as scar (1390 ± 8.7 vs 1276 ms ± 20.5, P < 0.01). There was no difference in the relative difference between remote myocardium and regions defined as scar, between groups (111.4 ms ± 7.6 vs 133.2 ms ± 17.5, P = 0.26).

Conclusions: Areas of MF are identifiable on native T1 maps, but absolute thresholds to define extent of MF could not be determined. Histological studies are needed to assess the ability of native-T1 signal-thresholding techniques to define extent of MF in haemodialysis patients. Data is taken from the PRIMID-AS (NCT01658345) and CYCLE-HD studies (ISRCTN11299707).

Keywords: Aortic stenosis; Haemodialysis; LGE; Myocardial fibrosis; Native T1.

Conflict of interest statement

Ethics approval and consent to participate

Both PRIMID-AS and CYCLE-HD received ethical approval from the National Research Ethics Service Committee East Midlands (REC references 11/EM/0410 and 14/EM/1190, respectively). All participants gave written and informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

a Mid-ventricular LGE image of an AS patient with LGE scored 1 (diffuse subtle enhancement). Enhancement seen at RV inferior insertion point and septal mid-wall (arrows). b Mid-ventricular LGE image of AS patient scored 2 (strong and discrete enhancement). Discrete enhancement seen at RV inferior insertion point (arrow). c Mid-ventricular native T1 map of the same patient shown in Fig. ‘1a’. Areas of discretely increased signal visible in the same distribution as enhancing areas on LGE image (arrows) d Mid-ventricular native T1 map of the same patient shown in Fig. ‘1b’. Discrete area of increased native T1 signal clearly visible at RV insertion point (arrow)

Fig. 2

a: Native T1 map of a haemodialysis patient. Region of interested (white) defining visual area of greatest signal increase at right ventricular inferior insertion point. Black arrow shows septal mid-wall discretely increased native T1 signal b: The same Native T1 in CMR42 tissue characterization module set T1 threshold defined by the global native T1 for the patient plus the standard deviation of the region of interest circled as the area of highest signal increase (defined in Argus in 1A) (T11SD technique). c: Mid-ventricular late gadolinium enhanced image of an aortic stenosis patient analysed using full-width half-maximum in the CMR-42 tissue characterization module. d: Corresponding native T1 map of the same patient with aortic stenosis analysed with T11SD technique

Fig. 3

Flow diagram of patients included in study and numbers of patients with areas of discretely increased signal on native T1 maps

Fig. 4

Circumferential native T1 in haemodialysis patients with areas of visually increased signal, haemodialysis patients without areas of visually increased signal and aortic stenosis patients with areas of visually increased signal

Fig. 5

a: Comparison of corresponding areas of discretely increased signal on native T1 in aortic stenosis patients with LGE images scored ‘1’ and scored ‘2’. b: Native T1 signal within region of discrete signal increase in haemodialysis patients compared to native T1 signal within region of discrete signal increase in aortic stenosis patients. c: Difference in native T1 between remote myocardium and myocardium within areas of discretely increased signal between haemodialysis and aortic stenosis patients. ms, milliseconds; HD, haemodialysis,; AS, aortic stenosis; LGE, late gadolinium enhancement

Fig. 6

a: Percentage area defined as scar by T11SD on native T1 mapping compared to percentage area defined as scar by FWHM on LGE images in AS patients. b: Comparison of extent of scar defined by T11SD between aortic stenosis patients and patients on haemodialysis. AS, aortic stenosis; HD, haemodialysis