Light Chain and Transthyretin Amyloidosis and Extracellular Volume Fraction by CT

Among patients with amyloidosis, extracellular volume fraction measured by computed tomography is correlated with adverse myocardial remodeling parameters.

Among patients with light chain (AL) and transthyretin (ATTR) amyloidosis, extracellular volume fraction by computed tomography (ECVCT) is correlated with adverse myocardial remodeling parameters and is independently associated with all-cause mortality in the ATTR subtype, researchers reported in JACC: Cardiovascular Imaging.

Study participants received 12-lead electrocardiography, echocardiography, assays of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT), and the 6-minute walk test from January 2013 to February 2016. Patients with ATTR also received technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy, and those with AL also received serum amyloid protein component scintigraphy.

A total of 72 patients with a confirmed diagnosis of AL (n=35) or ATTR (n=37) amyloidosis were included. Participants’ overall median age was 67 (IQR, 59-76) years, 70.8% were men, and the mean septal ECV was 49±14%. Patients with ATTR amyloidosis had significantly increased septal ECV percentages vs those with the AL subtype (56%±11% vs 43%±13%, respectively; P <.001).

Septal ECV was significantly correlated with left ventricular mass index (r=0.426; P <.001), left ventricular ejection fraction (r=0.460; P <.001), and biomarkers of myocardial injury (NT-proBNP [r=0.563; P <.001] and hsTnT [r=0.546; P <.001]).

ECV quantified by cardiac CT has the potential to improve recognition of cardiac amyloidosis.

ECV percentages were correlated with increased cardiac involvement in patients with AL amyloidosis (Mayo stage; rs=0.575; P =.003) and ATTR amyloid (Perugini grade; rs=0.483; P =.002).

Overall, after a mean follow-up of 5.3±2.4 years, 40 patients died.

Within the ATTR group, 70.3% of participants died after a mean follow-up of 5.1±2.4 years. Septal ECVCT was independently associated with mortality in the patients with ATTR according to multivariate Cox regression analysis adjusted for age and septal wall thickness (hazard ratio [HR], 1.046 [95% CI, 1.003-1.090]; P =.037). Global ECVCT was not associated with mortality in univariate analysis (HR, 1.037 [95% CI, 0.942-1.141]; P =.451).

Among the AL group, 40.0% of patients died after a mean follow-up of 5.5±2.4 years. The participants who died had significantly higher levels of NT-proBNP and average global ECV at baseline. Also, global ECV at baseline was a significant predictor of all-cause mortality in Cox regression univariate analysis (HR, 1.090 [95% CI, 1.016-1.169]; P =.016), compared with septal ECV (HR, 0.989 [95% CI, 0.941-1.040]; P =.667).

In addition, 57.0% of patients had cardiac magnetic resonance (CMR) at enrollment. ECVCT was significantly correlated with the results attained with CMR (r=0.8; P <.001), although it failed to predict the outcome in patients with AL (P =.545). ECVCMR was significantly associated with the outcome among patients in the ATTR group (HR, 1.018 [95% CI, 1.001-1.082]; P =.042), with a similar receiver operating characteristic curve as ECVCT (C-index, 0.680 vs 0.720; P =.957).

Study limitations include the population size, all participants are recruited from a national referral center, and the only outcome variable is all-cause mortality. Also, only half of the sample have simultaneous global ECVCT and/or ECVCMR measurements, which restricted comparison between acquisitions.

“ECV quantified by cardiac CT has the potential to improve recognition of cardiac amyloidosis,” the investigators wrote. “ECVCT replicates previous findings of CMR but is faster to acquire, is less claustrophobic, has widespread availability, and is significantly cheaper. ECVCT may address the need for better identification and risk stratification of amyloid patients, using a widely available imaging modality.”

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Gama F, Rosmini S, Bandula S, et al. Extracellular volume fraction by computed tomography predicts long-term prognosis among patients with cardiac amyloidosis. JACC Cardiovasc Imaging. Published online October 19, 2022. doi: 10.1016/j.jcmg.2022.08.006