1. AMYLOID AND AF: WHAT ARE WE MISSING?
Wael A. Jaber, MD, FACC, FESC
Imaging Section
Cleveland Clinic
Cleveland, OH

2. Low Flow, prothrombotic status with
Cardiac involvement AL
TTR (Focus of the talk)
Low Flow, prothrombotic status with
Increased atrial strain
Increased LA pressures
Loss of atrial contractility even in NSR

3. Cardiac Involvement: Clinical
CHF (“right sided”)
Heart failure with preserved EF (HFpEF)
“Hypertrophic cardiomyopathy”
Low flow low gradient aortic stenosis
Atrial fibrillation / cardioembolic stroke
Pacemaker / Complete heartblock
Angina w normal cors
Orthostasis
Neuropathy
Nephrotic syndrome (AL)
Macroglossia or periorbital purpura (AL)
Bilateral carpal tunnel syndrome (TTR >> AL)
Spinal stenosis (TTR)

4. TTR Cardiac Amyloid: Characteristic findings
Normal voltage ECG (up to 50%)
Concentric LV and RV wall thickening
Biatrial dilatation
Restrictive filling pattern with low E’
Interatrial septal thickening
Preserved EF early on
Systolic dysfunction as disease progresses

5. Lysosomal storage disease
JACC 2010;55:
HCM
Amyloid
HTN & renal failure
Lysosomal storage disease
Cardiac Oxalosis
Frederich’s Ataxia

6. Diagnosis Cardiac Amyloid by MRI: confusing phenotypes
Asymmetrical septal left ventricular hypertrophy (LVH) was present in 79% of patients with ATTR.

7. Tc PYP in TTR
European Heart Journal – Cardiovascular Imaging (2014) 15, 1289–1298

8. Better recognition of disease
New treatments to prolong survival
How often do we see afib in amyloid?
Do patients with amyloid have higher incidence of LA thrombi with and without afib?

9. Amyloid and Afib: Disease Prevelance
116 autopsies or explanted hearts at Mayo Clinic
Intracardiac thrombi were identified in 45 (39%) of 116 hearts.
(Circulation. 2007;116: )

10. Thrombi in patient with and without atrial fibrillation
23 embolic events occurred in patients with amyloidosis.
19 emboli were fatal and 4 were nonfatal

11. Predictors of Embolic Events
44% of death attributed to thrombo-embolic events

12. Left atrial appendage thrombi prevalence on TEE
66 year old male with known wild type transthyretin-related cardiac amyloidosis and persistent atrial fibrillation, recently hospitalized for decompensated heart failure and atrial fibrillation.
Apixaban started
TEE was performed 8 weeks later, revealing extensive left atrial appendage thrombus. Thus, DCCV was not performed.
Apixaban was replaced with warfarin with goal INR 2-3.
Returned to clinic after 8 weeks of therapeutic anticoagulation with warfarin.
Repeat TEE revealed persistent layered left atrial thrombus with sludge.

13. Left atrial appendage thrombi prevalence on TEE
1st TEE nd TEE

14. Left atrial appendage thrombi prevalence on TEE
120 TEEs were analyzed in 93 patients (age 70 ± 11 years, 71% male, 64% transthyretin amyloidosis).
Primary rhythm, CHADS2 score, and anticoagulation status at the time of TEE were defined.
Patients were categorized by presence of high-risk left atrial appendage findings: thrombus, sludge, or spontaneous echo contrast.
Presence of right atrial thrombus was also defined.
Results were compared to published historical controls from the ACUTE I and II trials.
Vakamudi S, Jaber WA et al , JACC 2017

15. Left atrial appendage thrombi prevalence on TEE

16. The prevalence of high-risk left atrial appendage findings was 44% in the cohort.
Left atrial appendage thrombus in patients in atrial fibrillation or flutter was higher than historical controls (28% versus 13.8%).
In patients with atrial fibrillation or flutter, the prevalence of high-risk atrial findings was 71%.
The CHADS2 score was not significantly associated with high-risk left atrial findings after adjusting for atrial fibrillation/flutter, anticoagulation, and ejection fraction (p=0.789).

18. DC cardioversion in amyloid heart disease
All on anticoagulation at time of TEE, none on DOACs

19. DC cardioversion in amyloid heart disease

20. DC cardioversion in amyloid heart disease

21. DC cardioversion in amyloid heart disease
Reasons for canceling DC cardioversion

22. DC cardioversion in amyloid heart disease

23. DC cardioversion in amyloid heart disease

24. Conclusions
Diagnosis of Cardiac amyloid (TTR) is on the rise given better non-invasive diagnostic tools.
Risk of intracardiac thrombi is times higher with amyloid heart disease.
Thrombi can form even in NSR
CHADS2 and CHADS-Vasc scores may underestimate the true risk of atrial thrombi in patients with cardiac amyloidosis.
Cardiac amyloidosis is a risk factor for the formation of atrial thrombi not reflected in the CHADS2 score

25. Conclusions
Given the predisposition to thrombus formation, patients we would not recommend electively cardioverting patients without a TEE regardless of anticoagulation status, duration of Afib or CHADS-vasc score.
Select patients may be candidates for prophylactic left atrial appendage closure devices to prevent initial thrombus formation.

26. Conclusions
Success rate of Afib ablation in patients presenting with amyloid heart disease is unclear.