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Abstract
Objectives Cardiac failure caused by transthyretin amyloidosis (ATTR) is an underdiagnosed clinical entity which has an important overlapping clinical phenotype with hypertrophic cardiomyopathy (HCM). Native myocardial T1 mapping by CMR is useful for diagnosis in cardiac amyloidosis. Here, we investigate the diagnostic and prognostic value of T1 mapping in the largest ATTR population studied so far as well as patients with HCM. We aimed to: 1) assess the ability of native T1 to diagnose cardiac amyloidosis; 2) compare native T1 to extracellular volume (ECV), and; 3) stratify prognosis.
Methods 134 wild-type ATTR (ATTRwt) (122 males, age 76±7 years), 95 mutant-type (ATTRm) (64 males, age 66±12 years) and 12 mutation carriers (4 males, age 46±8 years) were compared to 44 HCM patients. All subjects underwent CMR with standard SSFP-cine imaging, T1 mapping and ECV measurement. ATTR patients underwent 99mTc-DPD scintigraphy, the current diagnostic imaging reference standard for ATTR, with uptake determined by semi-quantitative score.
Results Native T1 and ECV were elevated in ATTR compared to HCM (p<0.001) (mean T1: in ATTRwt 1091±52 ms, in ATTRm 1084±68 ms, in HCM 1026±64 ms; mean ECV: in ATTRwt 0.6±0.1, in ATTRm 0.58±0.2 ms, in HCM 0.38±0.1 ms). No significant difference between native T1 and ECV was found between ATTRwt and ATTRm. Native T1 and ECV diagnostic performance was similar for ATTRwt and ATTRm (vs HCM: T1 AUC 0.89; ECV AUC 0.93; p=0.11 for the significance of the difference between areas under the ROC curves). During follow-up, 63 deaths occurred: 34 ATTRwt, 29 ATTRm. Whilst native T1 was not predictive of death, ECV was (HR, 1.130; 95% confidence interval, 1.06–1.2; p<0.001) and remained independent after adjustment for age, N-terminal pro b-type natriuretic peptide, left ventricular (LV) ejection fraction, E/E’, LV mass index, global longitudinal strain and tricuspid annular plane systolic excursion.
Conclusions CMR-determined native myocardial T1 and ECV provide excellent diagnostic accuracy for identification of ATTR cardiac amyloidosis and both variables track DPD-determined amyloid burden well. In this study, whilst T1 was not a predictor of mortality, ECV was independently associated with mortality.
Diagnostic performance and prognostic capability. (A) Receiver operator characteristics curve (ROC) for the discrimination of possible or definite transthyretin (ATTR) cardiac amyloidosis by native T1 and ECV from HCM. Kaplan-Meier survival curves for (B) pre-contrast myocardial T1 and (C) extracellular volume at bolus. The median native myocardial T1 (1092ms) (B) and median extracellular volume (ECV) (0.61) (C) were used as the respective cut points for survival.
Characteristics Examples from CMR Scans. CMR end-diastolic cine (far left), shortened modified look locker inversion recovery native T1 map (middle) and late gadolinium enhancement (LGE) images (far right), in two patients with definite transthyretin amyloidosis (ATTR amyloidosis), one (top) with normal T1 map, mildly eleveted native myocardial T1 (1039ms) and very elevated ECV (0.7), the other (bottom) with abnormal T1 map, markedly elevated native myocardial T1 (1224ms) and very elevated ECV (0.7).