Due to being frequently underdiagnosed and historically experiencing shorter life expectancies, patients with CA have been overlooked or excluded from numerous clinical trials. Medications aimed at controlling heart rate are often poorly tolerated, and there is a lack of comprehensive data in the literature regarding rhythm control approaches, including anti-arrhythmic therapy and ablation. The scarcity of robust evidence and the complexities involved in managing these arrhythmias further compound the challenges in the clinical monitoring of these patients.

There is insufficient solid evidence to definitively establish the superiority of rhythm control over heart rate control in managing cardiac arrhythmias CA.

In a retrospective analysis led by Mints et al., it was concluded that there was no reduced mortality associated with rhythm control under antiarrhythmic drugs, including amiodarone, sotalol, dofetilide, or propafenone, when compared to rate control strategies. Although the evidence remains limited, expert consensus suggests that maintaining patients in sinus rhythm is advisable.⁵

Given the crucial role of atrial contraction in determining left ventricular filling among CA patients, a strategy focused on rhythm control is favored over rate control, especially for symptomatic individuals. Amiodarone stands out as an anti-arrhythmic medication due to its favorable tolerability among the CA population. While flecainide and propafenone are effective in maintaining sinus rhythm in those with paroxysmal AF, their utility in CA patients is restricted. In cases where rhythm control proves ineffective, transitioning to rate control becomes necessary despite its inherent challenges.

Patients with CA habitually exhibit significant diastolic dysfunction with restrictive features. This condition necessitates compensatory tachycardia to maintain sufficient cardiac output. Consequently, the utilization of beta-blockers, calcium-channel blockers, and digoxin warrants careful consideration in CA patients due to their potential to depress compensatory heart rate response. This depression can significantly impact cardiac output, contributing to the poor tolerance observed with these medications in CA. Beta-blockers and non-dihydropyridine calcium channel blockers (CCBs) are typically the first-line choices for rate control in AF. Nevertheless, researchers caution against the use of non-dihydropyridine CCBs due to their negative impact on cardiac contractility and rhythm, as well as their association with increased hypotension risk. While beta-blockers may not be well tolerated by some patients, employing lower doses could still serve as an effective means of achieving rate control in AF cases with a swift ventricular response. The utilization of digoxin in amyloidosis remains a contentious topic due to its heightened potential for toxicity.^5,6

Tafamidis works by binding to ATTR, which prevents the dissociation of tetramers and the formation of amyloids. This medication has been associated with reductions in overall mortality and hospitalizations due to cardiovascular issues. Additionally, it helps slow down the decline in both functional capacity and quality of life compared to a placebo. A retrospective study involving 473 patients with CA concluded that, in univariate analysis, the use of tafamidis was linked to a lower incidence of AF, with a hazard ratio of 0.43 (p = 0.003).⁷

CA has been linked to a heightened risk of intracardiac thrombus, stroke, and systemic embolism when compared to the general population. Myocardial amyloid infiltration affecting both the right and left atria has been suggested as a pathophysiological mechanism leading to decreased atrial contractility, blood stagnation, endothelial dysfunction, and a relatively hypercoagulable state, which predisposes individuals to thrombus formation. Recent studies indicate that the presence of AF in CA patients may further increase the risk of intracardiac thrombus and stroke, suggesting that anticoagulation may be necessary for all patients regardless of their CHA2DS2-VASc score. While data from randomized controlled trials regarding the potential advantages of new oral anticoagulants versus vitamin K antagonists in CA patients with AF are lacking, recent evidence suggests that direct oral anticoagulants (DOACs) can be safely and effectively used in this patientpopulation.⁸

The utilization of direct current cardioversion in individuals with AF and CA has been documented, albeit with questionable outcomes regarding success and recurrence rates. Sanchis et al. noted a relatively elevated incidence of AF recurrence within three months (55%) and one year (70%) post-direct current cardioversion. Nonetheless, it should be noted that complications such as ventricular arrhythmia, bradyarrhythmia, hypoxemia, and stroke may pose greater risks in patients with CA.⁹

Data are scarce regarding the safety and effectiveness of catheter ablation for atrial arrhythmias in patients with CA. In a study by Donnellan et al., outcomes of 72 patients with ATTR-CA and AF were reported. Among them, 24 patients underwent catheter ablation, while a matched control group received medical management. Over a mean follow-up period of 39 +/- 26 months after ablation, the recurrence rate of AF was found to be 58%. However, compared to the medically managed group, those who underwent ablation exhibited lower rates of death, as well as hospitalization due to heart failure or arrhythmia. Ullah et al. utilized global health data from 148,133 patients diagnosed with AF and heart failure who underwent AF ablation. Within this dataset, a subgroup comprising 616 patients was identified, with 293 having concomitant AF-CA and 323 without CA. At index admission, AF ablation in patients with CA was associated with significantly higher adjusted odds of net adverse clinical events (MACE) [adjusted odds ratio (aOR) 4.21, 95% CI 1.7-5.20], in-hospital mortality (aOR 9.03, 95% CI 1.12-72.70) compared with non-CA-AF. Additionally, AF ablation in patients with CA, as opposed to those without CA, demonstrated comparatively increased rates of all-cause in-hospital mortality and net adverse events at the 30-day follow-up mark. These findings underscore the importance of conducting additional studies to ascertain whether AF ablation in the context of CA represents an effective strategy for rhythm control.^10-12