Quantification of Myocardial Extracellular Volume Fraction in Systemic AL Amyloidosis

Abstract

Background— Cardiac involvement predicts outcome in systemic AL amyloidosis and influences therapeutic options. Current methods of cardiac assessment do not quantify myocardial amyloid burden. We used equilibrium contrast cardiovascular magnetic resonance (EQ-CMR) to quantify the cardiac interstitial compartment, measured as myocardial extracellular volume (ECV) fraction, hypothesizing it would reflect amyloid burden. Methods and Results— Sixty patients with systemic AL amyloidosis (65% men, median age 65 years) underwent conventional clinical cardiovascular magnetic resonance, including late enhancement, equilibrium contrast cardiovascular magnetic resonance, and clinical cardiac evaluation, including ECG, echocardiography, assays of N-terminal pro-brain natriuretic peptide and Troponin T, and functional assessment comprising the 6-minute walk test in ambulant individuals. Cardiac involvement in the amyloidosis patients was categorized as definite, probable, or none, suspected by conventional criteria. Findings were compared with 82 healthy controls. Mean ECV was significantly greater in patients than healthy controls (0.25 versus 0.40, P <0.001) and correlated with conventional criteria for characterizing the presence of cardiac involvement, the categories of none, probable, definite corresponding to ECV of 0.276 versus 0.342 versus 0.488, respectively ( P <0.001). ECV was correlated with cardiac parameters by echocardiography (eg, Tissue Doppler Imaging [TDI] S-wave R=0.52, P<0.001) and conventional cardiovascular magnetic resonance (eg, indexed left ventricular mass R =0.56, P <0.001). There were also significant correlations with N-terminal pro-brain natriuretic peptide ( R =0.69, P <0.001) and Troponin T ( R =0.53, P =0.006). ECV was associated with smaller QRS voltages ( R =0.57, P <0.001) and correlated with poorer performance in the 6-minute walk test ( R =0.36, P =0.03). Conclusions— Myocardial ECV measurement has potential to become the first noninvasive test to quantify cardiac amyloid burden.

T1 Mapping in Characterizing Myocardial Disease

“…This is supported by histological data 45,51 on accumulation of diffuse fibrosis and the parallel relationships of T1 mapping with progressive ventricular remodeling and stiffness in DCM. 11,45,[83][84][85][86] Abnormal T1-mapping indices were also found in other common causes of DCM, including patients with cardiac amyloidosis, [87][88][89] diabetic cardiomyopathy, 34,90 and iron overload cardiomyopathies. 91 Native T1 mapping may also become of utility in patients with congenital heart disease and heart transplantation for rejection, 44,92,93 whose monitoring currently relies on repetitive invasive investigations.…”

“…T1-mapping indices are informative for the presence of myocardial infiltration, including myocardial amyloid, [87][88][89] iron or lipid deposition deciphering the subclinical myocardial involvement in iron overload, and Anderson-Fabry disease, respectively. 91,106,107 From a clinical perspective, T1 indices can support differentiation of the infiltrative hypertrophic phenocopies in suspected cardiac amyloid infiltration: normal T1 indices can virtually exclude the presence of amyloid disease.…”

Amyloid cardiomyopathy

“…In AL amyloid patients, ECV correlated directly with LV mass, TDI "S" wave, brain natriuretic peptide (BNP) and troponin levels, suggesting that ECV may represent a marker of amyloid burden in the heart 61 . Late gadolinium enhancement, T1 prolongation, and extracellular volume expansion may be observed in amyloidosis, other infiltrative diseases, inflammation, and fibrosis.…”

Nuclear Tracers for Transthyretin Cardiac Amyloidosis

“…Although cardiac magnetic resonance imaging can identify patterns that might better separate cardiac amyloidosis from other processes, substantial overlap remains in imaging characteristics between AL and ATTR. 9,10 Cardiac biopsy can clarify the diagnosis by identifying the precursor protein through histological or mass spectrometry techniques but is not feasible for all patients with suspected disease because of the risks associated with the procedure.…”