Author + information
- Ana Martinez-Naharro, MD,
- Esther Gonzalez-Lopez, MD,
- Andrej Corovic, MD,
- Jesus G. Mirelis, MD, PhD,
- A. John Baksi, PhD,
- James C. Moon, MD,
- Pablo Garcia-Pavia, MD, PhD,
- Julian D. Gillmore, MD, PhD,
- Philip N. Hawkins, PhD and
- Marianna Fontana, MD, PhD∗ (, )@UCL
- ↵∗National Amyloidosis Centre, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, United Kingdom
Cardiac amyloidosis can affect all cardiac chambers. The infiltrative process results in biventricular wall thickening, systolic and diastolic ventricular dysfunction, and low cardiac output. Amyloid infiltration in the atria leads to mechanical dysfunction and atrial enlargement, which cause blood stasis and risk of thrombus formation. High prevalence of intracardiac thrombi has been identified in patients with cardiac amyloidosis at autopsy and using transesophageal echocardiography (TEE) (1). However, the detection of intracardiac thrombi during TEE may reflect referral bias. Cardiac magnetic resonance (CMR) is a sensitive noninvasive method for detecting intracardiac thrombi, offering a comparable and equally specific alternative to TEE for evaluation of thrombus in the left atrial appendage (LAA) (2).
We assessed the prevalence of intracardiac thrombi using CMR in a consecutive cohort of patients with cardiac amyloidosis. Three hundred twenty-four consecutive subjects were prospectively recruited at the National Amyloidosis Centre, London, and at Puerta de Hierro University Hospital, Madrid. We excluded patients with contraindications to CMR, including glomerular filtration rate <30 ml/min. All participants underwent CMR on 1.5-T clinical scanners, including a standard volumetric study with early gadolinium enhancement (EGE) and late gadolinium enhancement (LGE). The gadolinium-based contrast agent used was 0.1 mmol/kg of gadoterate meglumine (Dotarem, Guerbet S.A., Lanester, France). EGE of the LAA was acquired using a 5-mm contiguous stack through the LAA and an inversion time of 440 ms to confirm the presence or absence of thrombus (3) (Figure 1). LGE was acquired using magnitude and phase-sensitive inversion recovery reconstruction. In 300 patients, T1 mapping was acquired, and the extracellular volume (ECV) was calculated (4). EGE images were reviewed blind (by A.M.N. and M.F.).
Of 324 patients with cardiac amyloidosis (256 male, 79%; 71 ± 11 years of age), 166 had amyloid transthyretin amyloidosis (ATTR), 155 had light chain amyloidosis (AL), 2 had apolipoprotein A-I, and 1 had apolipoprotein A-IV.
Two patterns of LGE were observed: subendocardial and transmural (4). Both patterns were present in AL (45.8% vs. 54.2%) and ATTR (27.1% vs. 72.9%). ECV was 0.51 in AL and 0.55 in ATTR (p < 0.01).
The prevalence of atrial fibrillation (AF) was 29%, and 1.5% had atrial flutter. The prevalence of AF was higher in ATTR than in AL (46.4% vs. 14.2%; p < 0.001). The prevalence of intracardiac thrombi was 6.2% (95% confidence interval [CI]: 3.5% to 8.8%) in the overall population, 5.2% (95% CI: 1.6% to 8.7%) in AL, and 7.2% (95% CI: 3.3% to 11.2%) in ATTR (p = 0.45). Of the patients with intracardiac thrombi (n = 20), 13 patients were in AF and 7 in sinus rhythm.
Overall, the prevalence of thrombi in patients in AF/flutter was high (13.1%), 9.1% in AL, and 14.3% in ATTR (p = 0.52). All the patients with intracardiac thrombi in AF were under long-term anticoagulation (46% with warfarin and 54% with direct oral anticoagulants). The prevalence of intracardiac thrombi in patients in sinus rhythm and AL amyloidosis was 4.5%, whereas in ATTR, it was 1.1% (p = 0.11). Most of the intracardiac thrombi (longest diameter 14.0 ± 7.7 mm) were found in the LAA (90%), however, 6 patients had thrombi in other locations (30%); 2 of them in isolation (without thrombi in the LAA), and 4 patients had thrombi in other locations as well as in the LAA (2 patients in the right atrial appendage, 1 in the left atrium, 1 patient had multiple thrombi).
The presence of intracardiac thrombi was significantly higher in patients with more severe biventricular systolic dysfunction (stroke volume p < 0.01; ejection fraction p < 0.05; mitral annular plane systolic excursion p < 0.01; tricuspid annular plane systolic excursion p < 0.01; and global longitudinal strain p < 0.01), atrial dilatation (left atrium p < 0.05; right atrium p < 0.01), and more severe degree of amyloid infiltration (ECV p < 0.01). Intracardiac thrombi was associated with higher levels of NT pro-BNP (p < 0.01) and AF (p < 0.05).
This is the first study to our knowledge to report the prevalence of intracardiac thrombi in a consecutive cohort of patients with cardiac amyloidosis. In contrast to the general anticoagulated AF population, in whom the prevalence of LAA thrombi has been reported to be <3% (5), we report a high prevalence of intracardiac thrombi in AF associated with cardiac amyloidosis despite anticoagulation (13.1%). Our results do not support the use of current recommendations for cardioversion after 3 weeks of anticoagulation in cardiac amyloidosis patients in AF, rather we suggest the need for specific imaging to exclude intracardiac thrombi before undergoing cardioversion. Intracardiac thrombi were also found in a significant number of patients in sinus rhythm, meriting further research to determine whether these patients benefit from prophylactic anticoagulation.
Please note: This work was supported by the Instituto de Salud Carlo III (ISCIII) (PI17/01941, PI18/00765 and CB 16/11/00432). Grants from ISCIII are supported by the Plan Estatal de I+D+I 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe.” Dr. Fontana is funded by the BHF grant FS/18/21/33447. Dr. Gonzalez-Lopez has received consulting and speaking fees from Pfizer. Dr. Garcia-Pavia has received consulting fees from Akcea, Alnylam, Eidos, Neuroinmmune, Pfizer, and Prothena; has received speaking fees from Akcea, Alnylam, Eidos, Pfizer, and Prothena; and has received research funding from Alnylam, Pfizer, and Prothena. Prof. Moon has received an unrestricted research grant from GlaxoSmithKline; and has also been paid a consultancy fee for trial design. Dr. Gillmore has been an advisory board member for Alnylam and Akcea. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
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