ECV per unit of myocardial thickness as a potential sign of transthyretin cardiac amyloidosis on CMR

Background/Introduction CMR is often employed to assess patients with unexplained left ventricular hypertrophy (LVH), which may be caused by transthyretin cardiac amyloidosis (TTR-CA). Expansion of extracellular volume (ECV) is hallmark of CA. As ECV equalizes or becomes greater than hematocrit level, a specific pattern of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is seen. However, it is a sign of late-stage disease and early identification of TTR-CA by CMR is challenging. Purpose To identify early signs of TTR amyloid cardiomyopathy by CMR. Methods We retrospectively analyzed a cohort of patients with confirmed wild-type transthyretin CA (TTR-CA) with available CMR scans (Siemens MAGNETOM Skyra, 3T) to identify patients who did not present with classical CMR LGE pattern – early TTR-CA group. A comparison of LV ejection fraction (LVEF), right ventricular EF (RVEF), LV myocardial mass index (MMI), ECV and ECV per millimeter of LV thickness (average of basal and mid-ventricular ECV divided by average of basal and mid-ventricular wall thickness) was made between early and classical TTR-CA groups, as well as with cohort with different forms of LVH: gene-positive hypertrophic cardiomyopathy (HCM) and severe aortic stenosis (AS). Results Out of 28 patients with TTR-CA (68% males, median age 73 [68-78]), 5 patients (80% females, median age 75) presented without classical signs of CA on LGE CMR (early CA group). Comparison between early CA and classical CA groups revealed significant differences in LVEF (60.6±5.5% vs 50.7±8.1%, p=0.01), RVEF (67.8±2.3% vs 57.6±12%, p=0.01), LV MMI (68±18.8 g/m2 vs 106±22 g/m2, p=0.01), and ECV (32.0±2.3% vs 47.68±9.9%, p<0.001), while ECV/mm was similar between the groups (3.84±0.39 %/mm vs 4.19±0.9 %/mm, p=0.41). Early CA group in comparison with LVH cohort (18 patients (9 HCM and 9 AOS), median age 64.5 (62-71)) had similar LVEF and RVEF (60.6±5.5% vs 59.6±8.1% and 67.8±2.3% vs 70.1±7.6%, p=0.804 and 0.504, respectively), lower LV MMI (67.7±18 g/m2 and 99±25 g/m2, p=0.015), higher ECV (32.0±2.3% vs 25.2±2.6, p=0.001) and ECV/mm (3.84±0.39 %/mm vs 2.11±0.4 %/mm, p<0.001). Conclusions Early stage TTR-CA can be similar to other forms of LVH on LGE imaging. However, there is a rise of ECV/mm values in this group of patients. Both early and late stages of TTR-CA demonstrated comparable ECV/mm values, despite significant difference in ECV.