Author + information
- Received April 19, 2017
- Revision received February 12, 2018
- Accepted February 15, 2018
- Published online May 6, 2019.
- Daniel S. Knight, MBBS, MD(Res)a,∗,
- Giulia Zumbo, MDa,∗,
- William Barcella, PhDb,
- Jennifer A. Steeden, M.Eng, PhDc,
- Vivek Muthurangu, MDc,
- Ana Martinez-Naharro, MDa,
- Thomas A. Treibel, MBBSd,
- Amna Abdel-Gadir, MBBSd,
- Heerajnarain Bulluck, MBBS, PhDe,
- Tushar Kotecha, MBChBa,
- Rohin Francis, MBBSa,
- Tamer Rezk, MBBSa,
- Candida C. Quarta, MD, PhDa,
- Carol J. Whelan, MDa,
- Helen J. Lachmann, MDa,
- Ashutosh D. Wechalekar, MD, PhDa,
- Julian D. Gillmore, MD, PhDa,
- James C. Moon, MDd,
- Philip N. Hawkins, PhD, FMedScia and
- Marianna Fontana, MD, PhDa,∗ ()
- aNational Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom
- bDepartment of Statistical Science, University College London, United Kingdom
- cCentre for Cardiovascular Imaging, Institute of Cardiovascular Science, University College London and Great Ormond Street Hospital for Children, London, United Kingdom
- dBarts Heart Centre, St. Bartholomew’s Hospital, London, United Kingdom
- eThe Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, United Kingdom
- ↵∗Address for correspondence:
Dr. Marianna Fontana, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine (Royal Free Campus), University College London, Rowland Hill Street, London NW3 2PF, United Kingdom.
Objectives This cross-sectional study aimed to describe the functional and structural cardiac abnormalities that occur across a spectrum of cardiac amyloidosis burden and to identify the strongest cardiac functional and structural prognostic predictors in amyloidosis using cardiac magnetic resonance (CMR) and echocardiography.
Background Cardiac involvement in light chain and transthyretin amyloidosis is the main driver of prognosis and influences treatment strategies. Numerous measures of cardiac structure and function are assessed by multiple imaging modalities in amyloidosis.
Methods A total f 322 subjects (311 systemic amyloidosis and 11 transthyretin gene mutation carriers) underwent comprehensive CMR and transthoracic echocardiography. The probabilities of 11 commonly measured structural and functional cardiac parameters being abnormal with increasing cardiac amyloidosis burden were evaluated. Cardiac amyloidosis burden was quantified using CMR-derived extracellular volume. The prognostic capacities of these parameters to predict death in amyloidosis were assessed using Cox proportional hazards models.
Results Left ventricular mass and mitral annular plane systolic excursion by CMR along with strain and E/e’ by echocardiography have high probabilities of being abnormal at low cardiac amyloid burden. Reductions in biventricular ejection fractions and elevations in biatrial areas occur at high burdens of infiltration. The probabilities of indexed stroke volume, myocardial contraction fraction, and tricuspid annular plane systolic excursion (TAPSE) being abnormal occur more gradually with increasing extracellular volume. Ninety patients (28%) died during a median follow-up of 22 months (interquartile range: 10 to 38 months). Univariable analysis showed that all imaging markers studied significantly predicted outcome. Multivariable analysis showed that TAPSE (hazard ratio: 1.46; 95% confidence interval: 1.16 to 1.85; p < 0.01) and indexed stroke volume (hazard ratio: 1.24; 95% confidence interval: 1.04 to 1.48; p < 0.05) by CMR were the only independent predictors of mortality.
Conclusions Specific functional and structural abnormalities characterize different burdens of cardiac amyloid deposition. In a multimodality imaging assessment of a large cohort of amyloidosis patients, CMR-derived TAPSE and indexed stroke volume are the strongest prognostic cardiac functional markers.
↵∗ Drs. Knight and Zumbo contributed equally to this work and are joint first authors.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 19, 2017.
- Revision received February 12, 2018.
- Accepted February 15, 2018.
- 2019 American College of Cardiology Foundation
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