Left Ventricular Structure and Function in Transthyretin-Related Versus Light-Chain Cardiac Amyloidosis

• Published in: Circulation (New York, N.Y.) Vol. 129; no. 18; pp. 1840 - 1849
• Main Authors: Quarta, Candida Cristina, Solomon, Scott D, Uraizee, Imran, Kruger, Jenna, Longhi, Simone, Ferlito, Marinella, Gagliardi, Christian, Milandri, Agnese, Rapezzi, Claudio, Falk, Rodney H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD by the American College of Cardiology Foundation and the American Heart Association, Inc 06.05.2014; Lippincott Williams & Wilkins
• Subjects: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial - metabolism; Amyloid Neuropathies, Familial - mortality; Amyloid Neuropathies, Familial - pathology; Amyloidosis; Amyloidosis - metabolism; Amyloidosis - mortality; Amyloidosis - pathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiomyopathies - diagnostic imaging; Cardiomyopathies - metabolism; Cardiomyopathies - mortality; Cardiovascular system; Diastole - physiology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Echocardiography; Female; Follow-Up Studies; Heart; Humans; Immunoglobulin Light Chains - metabolism; Incidence; Investigative techniques, diagnostic techniques (general aspects); Longitudinal Studies; Male; Medical sciences; Metabolic diseases; Middle Aged; Multivariate Analysis; Myocarditis. Cardiomyopathies; Other metabolic disorders; Prealbumin - metabolism; Prevalence; Prognosis; Systole - physiology; Ultrasonic investigative techniques; Ventricular Function, Left - physiology; Sonography; Heart; amyloidosis, hereditary, transthyretin-related; Echocardiography; Cardiomyopathy; transthyretin; Metabolic diseases; Cardiovascular disease; Light peptide chain; Hereditary; Enzymopathy; Myocardial disease; Protein; Genetic disease; Thyroxine binding prealbumin; Heart disease; Amyloid; Amyloidosis; Circulatory system; Cardiology; Left ventricle performance; Structure; cardiomyopathies; Comparative study; amyloid; echocardiography
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.113.006242

BACKGROUND—Immunoglobulin amyloid light-chain (AL)-related cardiac amyloidosis (CA) has a worse prognosis than either wild-type (ATTRwt) or mutant (ATTRm) transthyretin (TTR) CA. Detailed echocardiographic studies have been performed in AL amyloidosis but not in TTR amyloidosis and might give insight into this difference. We assessed cardiac structure and function and outcome in a large population of patients with CA and compared findings in TTR and AL-related disease. METHODS AND RESULTS—We analyzed 172 patients with CA (AL amyloidosis, n=80; ATTRm, n=36; ATTRwt, n=56) by standard echocardiography and 2-dimensional speckle-tracking imaging-derived left ventricular (LV) longitudinal (LS), radial, and circumferential strains. Despite a preserved LV ejection fraction (55±12%), LS was severely impaired in CA. Standard measures of LV function and speckle-tracking imaging worsened as wall thickness increased, whereas apical LS was preserved regardless of the pathogenesis of CA and the degree of wall thickening. Compared with ATTRm and AL amyloidosis, ATTRwt was characterized by greater LV wall thickness and lower ejection fraction. LS was more depressed in both ATTRwt and AL amyloidosis (−11±3% and −12±4%, respectively, P=0.54) than in ATTRm (−15±4%, P<0.01 versus AL amyloidosis and ATTRwt). TTR-related causes were favorable predictors of survival, whereas LS and advanced New York Heart Association class were negative predictors. CONCLUSIONS—In patients with CA, worsening LV function correlated with increasing wall thickness regardless of pathogenesis. Patients with ATTRwt had a statistically greater wall thickness but lesser mortality than those with AL amyloidosis, despite very similar degrees of LS impairment. This paradox suggests an additional mechanism for LV dysfunction in AL amyloidosis, such as previously demonstrated light-chain toxicity.