Atrial arrhythmias may cause significant clinical deterioration in patients with cardiac amyloidosis (CA). A small retrospective study of 58 patients with CA found a high incidence of left atrial appendage thrombus (LAAT) by transesophageal echocardiogram (TEE) performed before direct current cardioversion (DCCV),1 and based on these findings, a recent expert consensus document recommended routine pre-DCCV TEE in CA patients regardless of preprocedural anticoagulation duration.2 This approach is different from standard DCCV guidelines for preprocedural TEE in the general population, which limit recommendations for TEE to patients with inadequate preprocedure anticoagulation. Because our practice in CA patients is to follow standard guidelines for pre-DCCV TEE for the restoration of sinus rhythm, we assessed our experience in a considerably larger population than the previously published study, focusing on the safety of this approach.
We conducted a retrospective analysis of patients undergoing DCCV for atrial arrhythmia between 2012 and 2022 in 2 teaching hospitals within the Mass General Brigham health care system (1 of which had an active amyloidosis program). All scheduled DCCV procedures were recorded, including those canceled because LAAT was detected by TEE (which were performed at the discretion of the treating physician). Each DCCV procedure was considered an independent case. The prevalence of postprocedural clinical stroke (cerebrovascular accidents or transient ischemic attacks) within 48 hours was assessed, and arrhythmia recurrence by 12 months postprocedure was evaluated using Cox proportional hazards model incorporating Fine and Gray’s methodology. The study protocol was approved by the Massachusetts General Brigham Institutional Review Board.
A total of 192 DCCV procedures were scheduled in 108 patients, with 156 (81%) procedures performed in 86 transthyretin CA patients and 36 (19%) procedures in 22 light-chain CA patients. The median age of the group was 79 years (Q1-Q3: 73–82 years) with male predominance (82%). Prior stroke or thromboembolic events had occurred in 9%, and the median CHA2DS2-VASc score was 3.0. Preprocedure therapy with a diuretic agent was required in 72% (n = 113), and 73% of procedures (n = 140) involved a non-vitamin K antagonist oral anticoagulant.
TEE was performed in 31% (n = 60) of scheduled DCCV procedures representing 47 individuals. Twenty-five (42%) TEE studies were performed without documented formal indication. Pre-DCCV TEE was more frequently performed among cardiologists not affiliated vs affiliated with the amyloidosis program (45% [37 of 82] vs 21% [23 of 110], respectively; P < 0.001), although the prevalence of inadequate anticoagulation as the underlying indication of preprocedural TEE was similar among both patient groups (P = 0.286). Among patients undergoing TEE, 12 (26%) had evidence of LAAT resulting in DCCV cancellation.
The breakdown of DCCV procedures and outcomes is presented in Figure 1. A total of 187 DCCV procedures were performed in 103 patients, with successful restoration of sinus rhythm in 99% (n = 185). There were no postprocedural clinical strokes and no procedural complications.
FIGURE 1. Breakdown of Outcomes in Scheduled DCCV Procedures.
The outcomes of 192 scheduled DCCV procedures as well as the findings of 60 TEE studies that were performed before DCCV. CA = cardiac amyloidosis; DCCV = direct current cardioversion; LAAT = left atrial appendage thrombus; TEE = transesophageal echocardiography.
The 1-year documented recurrence of atrial fibrillation (AF) following successful DCCV was 47% at a median of 35 weeks (Q1-Q3: 7–52 weeks) following the index cardioversion. Patients treated with an oral anti-arrhythmic drug following the index DCCV (n = 67; 63%) had a lower 1-year rate of AF recurrence (37% vs 60%; HR: 0.501; 95% CI: 0.29–0.87; P = 0.014). Statistically significant differences were not observed between the characteristics and outcomes of DCCV procedures in light-chain CA vs transthyretin CA patients, with comparable 1-year rates of AF recurrence.
These retrospective data suggest that DCCV can be safely performed in patients with CA without preprocedure TEE, provided adequate anticoagulation has been administered, and that DCCV in patients with CA has a high success rate with similar long-term sinus rhythm maintenance with the use of antiarrhythmic drugs as in nonamyloid patients.3 Although TEE was performed more frequently by nonamyloid program cardiologists, often without a standard indication, a more restrictive TEE approach was not associated with any thromboembolic events, despite the likely presence of LAAT in some of these patients. Our findings are consistent with the concept that post-DCCV thromboembolism is not a function of preformed thrombus dislodgement but, rather, the result of fresh thrombus formation/propagation associated with post-DCCV atrial stunning in inadequately anticoagulated patients.
We believe that our results challenge the current specialized recommendation for performing routine pre-DCCV TEE in CA patients, and we would argue that the high prevalence of LAAT does not translate to increased stroke risk in the presence of adequate anticoagulation. Moreover, routine TEE may lead to DCCV cancellation, condemning some patients to ongoing or persistent arrhythmia-associated clinical deterioration. We thus suggest that until a randomized controlled study of DCCV with and without routine TEE is performed in patients with CA, pre-DCCV TEE in this population should be limited to a subgroup of inadequately anticoagulated patients, similar to current guidelines for nonamyloid patients.
What is the clinical question being addressed?
What is the prevalence of post-DCCV stroke in cardiac amyloidosis patients while following standard guidelines for preprocedure TEE?
What is the main finding?
Although the rate of left atrial appendage thrombus was high, there were no strokes in adequately anticoagulated cardiac amyloidosis patients undergoing DCCV.
Acknowledgments
Dr Itzhaki Ben Zadok has received speaker fees from and served on Advisory Boards for Pfizer. Dr Cuddy has received speaker fees from Pfizer and Ionis; has served on Advisory Boards for BridgeBio, AstraZeneca, and Novo Nordisk; and has received research support from the National Institutes of Health (1K23HL166686-01) and American Heart Association (23CDA857664). Dr Clerc has received a research fellowship from the International Society of Amyloidosis and Pfizer. Dr Vijayakumar has received research support from National Heart, Lung, and Blood Institute T32 postdoctoral training grant T32HL094201 and from the Amyloidosis Foundation. Dr Dorbala has received research grants from Pfizer, Attralus, Siemens, and Philips; and has received consultant fees from Pfizer, Novo Nordisk, and AstraZeneca/Alexion. Dr Falk has received consultant fees from Alexion, Alnylam, Novo Nordisk, and Pfizer; and has received speaker fees from Alexion and Pfizer. Dr Gaggin has reported that she has no relationships relevant to the contents of this paper to disclose.
Footnotes
Review and acceptance occurred under Dr Valentin Fuster’s term as Editor-in-Chief.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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