Sarah A M Cuddy1, Paco E Bravo2, Rodney H Falk3, Samir El-Sady4, Marie Foley Kijewski4, Mi-Ae Park4, Frederick L Ruberg5, Vaishali Sanchorawala5, Heather Landau6, Andrew J Yee7, Giada Bianchi8, Marcelo F Di Carli9, Su-Chun Cheng10, Michael Jerosch-Herold11, Raymond Y Kwong11, Ronglih Liao12, Sharmila Dorbala13. 1. Department of Medicine, Division of Cardiology, Cardiac Amyloidosis Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Radiology, Division of Nuclear Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Medicine and Radiology, CV Imaging Program, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 2. Department of Radiology, Division of Nuclear Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Departments of Radiology and Medicine, Divisions of Nuclear Medicine and Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 3. Department of Medicine, Division of Cardiology, Cardiac Amyloidosis Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 4. Department of Radiology, Division of Nuclear Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 5. Section of Cardiovascular Medicine, Amyloidosis Center, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts. 6. Division of Medical Oncology, Memorial Sloan Kettering Medical Center, New York City, New York. 7. Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, Massachusetts. 8. Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 9. Department of Radiology, Division of Nuclear Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Medicine and Radiology, CV Imaging Program, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 10. Department of Data Sciences, Division of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts. 11. Department of Medicine and Radiology, CV Imaging Program, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 12. Amyloidosis Program, Stanford University, Stanford, California. 13. Department of Medicine, Division of Cardiology, Cardiac Amyloidosis Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Radiology, Division of Nuclear Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Medicine and Radiology, CV Imaging Program, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: sdorbala@bwh.harvard.edu.
Abstract
OBJECTIVES: The purpose of this study was to determine phenotypes characterizing cardiac involvement in AL amyloidosis by using direct (fluorine-18-labeled florbetapir {[18F]florbetapir} positron emission tomography [PET]/computed tomography) and indirect (echocardiography and cardiac magnetic resonance [CMR]) imaging biomarkers of AL amyloidosis. BACKGROUND: Cardiac involvement in systemic light chain amyloidosis (AL) is the main determinant of prognosis and, therefore, guides management. The hypothesis of this study was that myocardial AL deposits and expansion of extracellular volume (ECV) could be identified before increases in N-terminal pro-B-type natriuretic peptide or wall thickness. METHODS: A total of 45 subjects were prospectively enrolled in 3 groups: 25 with active AL amyloidosis with cardiac involvement (active-CA), 10 with active AL amyloidosis without cardiac involvement by conventional criteria (active-non-CA), and 10 with AL amyloidosis with cardiac involvement in remission for at least 1 year (remission-CA). All subjects underwent echocardiography, CMR, and [18F]florbetapir PET/CT to evaluate cardiac amyloid burden. RESULTS: The active-CA group demonstrated the largest myocardial AL amyloid burden, quantified by [18F]florbetapir retention index (RI) 0.110 (interquartile range [IQR]: 0.078 to 0.139) min-1, and the lowest cardiac function by global longitudinal strain (GLS), median GLS -11% (IQR: -8% to -13%). The remission-CA group had expanded extracellular volume (ECV) and [18F]florbetapir RI of 0.097 (IQR: 0.070 to 0.124 min-1), and abnormal GLS despite hematologic remission for >1 year. The active-non-CA cohort had evidence of cardiac amyloid deposition by advanced imaging metrics in 50% of the subjects; cardiac involvement was identified by late gadolinium enhancement in 20%, elevated ECV in 20%, and elevated [18F]florbetapir RI in 50%. CONCLUSIONS: Evidence of cardiac amyloid infiltration was found based on direct and indirect imaging biomarkers in subjects without CA by conventional criteria. The findings from [18F]florbetapir PET imaging provided insight into the preclinical disease process and on the basis of interpretation of expanded ECV on CMR and have important implications for future research and clinical management of AL amyloidosis. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145).
OBJECTIVES: The purpose of this study was to determine phenotypes characterizing cardiac involvement in AL amyloidosis by using direct (fluorine-18-labeled florbetapir {[18F]florbetapir} positron emission tomography [PET]/computed tomography) and indirect (echocardiography and cardiac magnetic resonance [CMR]) imaging biomarkers of AL amyloidosis. BACKGROUND: Cardiac involvement in systemic light chain amyloidosis (AL) is the main determinant of prognosis and, therefore, guides management. The hypothesis of this study was that myocardial AL deposits and expansion of extracellular volume (ECV) could be identified before increases in N-terminal pro-B-type natriuretic peptide or wall thickness. METHODS: A total of 45 subjects were prospectively enrolled in 3 groups: 25 with active AL amyloidosis with cardiac involvement (active-CA), 10 with active AL amyloidosis without cardiac involvement by conventional criteria (active-non-CA), and 10 with AL amyloidosis with cardiac involvement in remission for at least 1 year (remission-CA). All subjects underwent echocardiography, CMR, and [18F]florbetapir PET/CT to evaluate cardiac amyloid burden. RESULTS: The active-CA group demonstrated the largest myocardial AL amyloid burden, quantified by [18F]florbetapir retention index (RI) 0.110 (interquartile range [IQR]: 0.078 to 0.139) min-1, and the lowest cardiac function by global longitudinal strain (GLS), median GLS -11% (IQR: -8% to -13%). The remission-CA group had expanded extracellular volume (ECV) and [18F]florbetapir RI of 0.097 (IQR: 0.070 to 0.124 min-1), and abnormal GLS despite hematologic remission for >1 year. The active-non-CA cohort had evidence of cardiac amyloid deposition by advanced imaging metrics in 50% of the subjects; cardiac involvement was identified by late gadolinium enhancement in 20%, elevated ECV in 20%, and elevated [18F]florbetapir RI in 50%. CONCLUSIONS: Evidence of cardiac amyloid infiltration was found based on direct and indirect imaging biomarkers in subjects without CA by conventional criteria. The findings from [18F]florbetapir PET imaging provided insight into the preclinical disease process and on the basis of interpretation of expanded ECV on CMR and have important implications for future research and clinical management of AL amyloidosis. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145).
Authors: Sarah A M Cuddy; Michael Jerosch-Herold; Rodney H Falk; Marie Foley Kijewski; Vasvi Singh; Frederick L Ruberg; Vaishali Sanchorawala; Heather Landau; Matthew S Maurer; Andrew J Yee; Giada Bianchi; Marcelo F Di Carli; Ronglih Liao; Raymond Y Kwong; Sharmila Dorbala Journal: JACC Cardiovasc Imaging Date: 2021-12-15
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