Tushar Kotecha1, Ana Martinez-Naharro2, Thomas A Treibel3, Rohin Francis2, Sabrina Nordin3, Amna Abdel-Gadir3, Daniel S Knight4, Giulia Zumbo5, Stefania Rosmini6, Viviana Maestrini7, Heerajnarain Bulluck8, Roby D Rakhit9, Ashutosh D Wechalekar4, Janet Gilbertson5, Mary N Sheppard10, Peter Kellman11, Julian D Gillmore4, James C Moon6, Philip N Hawkins4, Marianna Fontana12. 1. National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom; Royal Free Hospital, London, United Kingdom. 2. National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom. 3. Institute of Cardiovascular Science, University College London, London, United Kingdom; Barts Heart Centre, London, United Kingdom. 4. National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom; Royal Free Hospital, London, United Kingdom. 5. National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom. 6. Barts Heart Centre, London, United Kingdom. 7. Barts Heart Centre, London, United Kingdom; Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology & Geriatric Sciences, "Sapienza" University of Rome, Rome, Italy. 8. Institute of Cardiovascular Science, University College London, London, United Kingdom. 9. Institute of Cardiovascular Science, University College London, London, United Kingdom; Royal Free Hospital, London, United Kingdom. 10. Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, United Kingdom. 11. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. 12. National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom; Royal Free Hospital, London, United Kingdom. Electronic address: m.fontana@ucl.ac.uk.
Abstract
BACKGROUND: Prognosis in light-chain (AL) and transthyretin (ATTR) amyloidosis is influenced by cardiac involvement. ATTR amyloidosis has better prognosis than AL amyloidosis despite more amyloid infiltration, suggesting additional mechanisms of damage in AL amyloidosis. OBJECTIVES: The aim of the study was to assess the presence and prognostic significance of myocardial edema in patients with amyloidosis. METHODS: The study recruited 286 patients: 100 with systemic AL amyloidosis, 163 with cardiac ATTR amyloidosis, 12 with suspected cardiac ATTR amyloidosis (grade 1 on 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid), 11 asymptomatic individuals with amyloidogenic TTR gene mutations, and 30 healthy volunteers. All subjects underwent cardiovascular magnetic resonance with T1 and T2 mapping and 16 underwent endomyocardial biopsy. RESULTS: Myocardial T2 was increased in amyloidosis with the degree of elevation being highest in untreated AL patients (untreated AL amyloidosis 56.6 ± 5.1 ms; treated AL amyloidosis 53.6 ± 3.9 ms; ATTR amyloidosis 54.2 ± 4.1 ms; each p < 0.01 compared with control subjects: 48.9 ± 2.0 ms). Left ventricular (LV) mass and extracellular volume fraction were higher in ATTR amyloidosis compared with AL amyloidosis while LV ejection fraction was lower (p < 0.001). Histological evidence of edema was present in 87.5% of biopsy samples ranging from 5% to 40% myocardial involvement. Using Cox regression models, myocardial T2 predicted death in AL amyloidosis (hazard ratio: 1.48; 95% confidence interval: 1.20 to 1.82) and remained significant after adjusting for extracellular volume fraction and N-terminal pro-B-type natriuretic peptide (hazard ratio: 1.32; 95% confidence interval: 1.05 to 1.67). CONCLUSIONS: Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTR amyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.
BACKGROUND: Prognosis in light-chain (AL) and transthyretin (ATTR) amyloidosis is influenced by cardiac involvement. ATTRamyloidosis has better prognosis than AL amyloidosis despite more amyloid infiltration, suggesting additional mechanisms of damage in AL amyloidosis. OBJECTIVES: The aim of the study was to assess the presence and prognostic significance of myocardial edema in patients with amyloidosis. METHODS: The study recruited 286 patients: 100 with systemic AL amyloidosis, 163 with cardiac ATTRamyloidosis, 12 with suspected cardiac ATTRamyloidosis (grade 1 on 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid), 11 asymptomatic individuals with amyloidogenic TTR gene mutations, and 30 healthy volunteers. All subjects underwent cardiovascular magnetic resonance with T1 and T2 mapping and 16 underwent endomyocardial biopsy. RESULTS: Myocardial T2 was increased in amyloidosis with the degree of elevation being highest in untreated ALpatients (untreated AL amyloidosis 56.6 ± 5.1 ms; treated AL amyloidosis 53.6 ± 3.9 ms; ATTRamyloidosis 54.2 ± 4.1 ms; each p < 0.01 compared with control subjects: 48.9 ± 2.0 ms). Left ventricular (LV) mass and extracellular volume fraction were higher in ATTRamyloidosis compared with AL amyloidosis while LV ejection fraction was lower (p < 0.001). Histological evidence of edema was present in 87.5% of biopsy samples ranging from 5% to 40% myocardial involvement. Using Cox regression models, myocardial T2 predicted death in AL amyloidosis (hazard ratio: 1.48; 95% confidence interval: 1.20 to 1.82) and remained significant after adjusting for extracellular volume fraction and N-terminal pro-B-type natriuretic peptide (hazard ratio: 1.32; 95% confidence interval: 1.05 to 1.67). CONCLUSIONS:Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTRamyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.
Authors: Sharmila Dorbala; Yukio Ando; Sabahat Bokhari; Angela Dispenzieri; Rodney H Falk; Victor A Ferrari; Marianna Fontana; Olivier Gheysens; Julian D Gillmore; Andor W J M Glaudemans; Mazen A Hanna; Bouke P C Hazenberg; Arnt V Kristen; Raymond Y Kwong; Mathew S Maurer; Giampaolo Merlini; Edward J Miller; James C Moon; Venkatesh L Murthy; C Cristina Quarta; Claudio Rapezzi; Frederick L Ruberg; Sanjiv J Shah; Riemer H J A Slart; Hein J Verberne; Jamieson M Bourque Journal: J Nucl Cardiol Date: 2019-12 Impact factor: 5.952
Authors: Srilakshmi Vallabhaneni; Kathleen W Zhang; Jose A Alvarez-Cardona; Joshua D Mitchell; Henning Steen; Pamela K Woodard; Daniel J Lenihan Journal: Int J Cardiovasc Imaging Date: 2021-05-12 Impact factor: 2.357
Authors: David N Firmin; Dudley J Pennell; Zohya Khalique; Pedro F Ferreira; Andrew D Scott; Sonia Nielles-Vallespin; Ana Martinez-Naharro; Marianna Fontana; Phillip Hawkins Journal: Circ Cardiovasc Imaging Date: 2020-05-15 Impact factor: 7.792
Authors: Kongkiat Chaikriangkrai; Muhannad Aboud Abbasi; Roberto Sarnari; Ryan Dolan; Daniel Lee; Allen S Anderson; Kambiz Ghafourian; Sadiya S Khan; Esther E Vorovich; Jonathan D Rich; Jane E Wilcox; Julie A Blaisdell; Clyde W Yancy; James Carr; Michael Markl Journal: JACC Cardiovasc Imaging Date: 2020-03-18