Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis

Abstract

Background: Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis.

Objectives: This study sought to investigate the association of extracellular volume fraction by computed tomography (ECV_CT), myocardial remodeling, and mortality in patients with systemic amyloidosis.

Methods: Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECV_CT was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (^99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECV_CT was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality.

Results: A total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age: 67 [IQR: 59-76] years, 70.8% male). Mean septal ECV_CT was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro-B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECV_CT increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECV_CT was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI: 1.003-1.090; P = 0.037).

Conclusions: Cardiac amyloid burden quantified by ECV_CT is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECV_CT may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.

Keywords: cardiac amyloidosis; computed tomography; extracellular matrix; myocardial extracellular volume fraction; myocardial fibrosis; myocardial tissue characterization.