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

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

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)

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

Lysosomal storage disease JACC 2010;55:1769-79 HCM Amyloid HTN & renal failure Lysosomal storage disease Cardiac Oxalosis Frederich’s Ataxia

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

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

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?

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: 2420-2426.)

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

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

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.

Left atrial appendage thrombi prevalence on TEE 1st TEE 2nd TEE

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

Left atrial appendage thrombi prevalence on TEE

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).

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

DC cardioversion in amyloid heart disease

DC cardioversion in amyloid heart disease

DC cardioversion in amyloid heart disease Reasons for canceling DC cardioversion

DC cardioversion in amyloid heart disease

DC cardioversion in amyloid heart disease

Conclusions Diagnosis of Cardiac amyloid (TTR) is on the rise given better non-invasive diagnostic tools. Risk of intracardiac thrombi is 2.5-3 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

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.

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