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Porcari et al. Vessel Plus 2022;6:33 https://dx.doi.org/10.20517/2574-1209.2021.134 Page 7 of 14

challenging because agents for rate and rhythm control may be poorly tolerated, and many patients have
atrial thrombi precluding the adoption of rhythm control strategies such as direct-current cardioversion
[32]
(DCCV) [Table 1] .

The management of AF in patients with CA can be clinically challenging requiring major decisions such as:
(1) rate vs. rhythm control strategy; (2) pharmacological vs. electrical therapy (DCCV or AF ablation); and
(3) anticoagulant therapy and estimation of the thromboembolic and bleeding risk.

Rate control
[26]
The rate control strategy represents the most common indication to start BBs in patients with CA . Safety
and tolerability are acceptable when BBs are prescribed at low doses for lenient control of the heart rate (<
[27]
110 bpm) . In addition, they might be indicated for concomitant conditions, such as coronary artery
disease. In the latest guidelines from the European Society of Cardiology , digoxin is recommended for
[33]
rate control of AF in patients with LVEF ≥ 40% (Class I, LOE B). However, digoxin use in CA has been
traditionally discouraged following in vitro studies reporting a tendency to bind to amyloid fibrils, thus
[34]
increasing the local drug concentrations and potentially resulting in toxic effects . As a consequence, CA is
considered an absolute contraindication to digoxin use due to the possibility of increased risk of toxicity
even with “therapeutic digoxin levels” . Nevertheless, the clinical significance of these findings is unclear
[35]
and digoxin in low doses, adjusted according to serum trough levels, has been used with acceptable
tolerability . A recent retrospective analysis of 107 AL patients treated with digoxin observed a relatively
[36]
low incidence of arrhythmias (11% of cases), almost exclusively in newly diagnosed patients . Ongoing
[35]
studies to shed light upon digoxin use in CA, whether clinicians decide to use this drug, drug
concentrations, and renal function should be closely monitored. Similar to digoxin, non-dihydropyridine
Ca blockers (i.e., verapamil) and nifedipine bind amyloid fibrils and should be avoided as they can
precipitate or worsen HF, even HFpEF, potentially resulting in advanced AV blocks and cardiogenic
shock [21,37,38] . Amiodarone is fairly well tolerated, particularly if administered orally, and is effective in
achieving rate control.

Rhythm control
Currently, there is not sufficient evidence to recommend pursuing the rhythm rather than rate control
strategy in CA. Biatrial dilatation is common in patients with CA and atrial function can be impaired in the
presence of advanced cardiac infiltration resulting in a modest end-diastolic contribution to ventricular
filling also in sinus rhythm. This makes rhythm control (i.e., DCCV) a less attractive option due to an
increased risk of arrhythmias relapse during follow up. In clinical practice, rhythm control options are
mainly considered in patients experiencing deleterious effects from drugs for rate control and in those with
significant symptom burden in the presence of AF [30,31] . However, a strategy including transesophageal
echocardiography before proceeding with pharmacological or electrical cardioversion could be reasonable
due to the increased frequency of atrial thrombosis observed even in patients under anticoagulant therapy
(up to 28% in recent series) .
[39]
Amiodarone is the agent of choice in most cases, but other antiarrhythmic drugs are also useful such as
dofetilide and propafenone . For most of them, close monitoring of the QT interval and renal function is
[21]
needed.

Non-pharmacological options include DCCV, AF ablation, and AV node ablation
Success rates of DCCV are similar in patients with and without CA (approaching 90%-95%) [31,40] . However,
CA patients require higher mean energy and multiple attempts to restore sinus rhythm and experience
more procedural complications (up to a seven-fold increase) compared to non-CA patients, including