Light Chain and Transthyretin Amyloidosis and Extracellular Volume Fraction by CT

Among patients with light chain (AL) and transthyretin (ATTR) amyloidosis, extracellular volume fraction by computed tomography (ECV_CT) 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 percentages were correlated with increased cardiac involvement in patients with AL amyloidosis (Mayo stage; r_s=0.575; P =.003) and ATTR amyloid (Perugini grade; r_s=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 ECV_CT 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 ECV_CT 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. ECV_CT 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). ECV_CMR 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 ECV_CT (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 ECV_CT and/or ECV_CMR measurements, which restricted comparison between acquisitions.

“ECV quantified by cardiac CT has the potential to improve recognition of cardiac amyloidosis,” the investigators wrote. “ECV_CT replicates previous findings of CMR but is faster to acquire, is less claustrophobic, has widespread availability, and is significantly cheaper. ECV_CT 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.