Atrial Fibrillation Prevalence and Its Management in Transfusion-Dependent Thalassemias: The Fathal Study
Authors: Di Stefano Valeria , Gianesin Barbara , Bertini Matteo , Culcasi Martina , Denotti Anna Rita , Derchi Giorgio , Giuditta Marianna , Longo Filomena , Manca Maria Regina , Martinoli Maria Cristina , Orecchia Valeria , Origa Raffaella , Motta Irene 
Published: December 2023

Atrial fibrillation (AF) represents an emerging issue in the thalassemia population related to increased life expectancy. However, data on AF in these patients are limited, and the current management is based on the guidelines for the general population. Nevertheless, AF in these patients has distinctive features that could require specific management.

We conducted a multicentric retrospective study supported by the Italian Society of Thalassemia and Hemoglobinopathies (SITE) to elucidate the prevalence of AF in transfusion-dependent thalassemia (TDT) adults in Italy and to study its management, particularly the use of transcatheter ablation and anticoagulation management. Patients followed between June 1, 2003 and May 31, 2023 with a diagnosis of alpha- or beta-transfusion-dependent thalassemia with at least one episode of AF were included in the study. Clinical data of patients have been retrospectively collected with dedicated digital case report form (CRF).

So far, 3 centers (Cagliari, Ferrara, Milano) have participated in the study. Eight-hundred-sixty-one adult TDT patients are regularly followed in the participating centers. Data from 130 adult TDT with AF were included. At enrollment, 119 patients were alive (71 males, 60%), the mean age at enrollment was 51.9 years, and 71% were splenectomized. Almost all (98%) had beta-thalassemia, of which 20% had thalassemia intermedia and became transfusion dependent during their life. The mean age at the first AF episode was 39.7 yr.

Overall, AF prevalence in TDT was 13.8%, with a significant rise above the age of 50 (age 51-65: prevalence 26.4%, age&gt;65 33.3%), differently from the general population in which the prevalence is 2-4%, and patients are older. As in the general population, prevalence was higher in males (18.2% vs 10.2%).

Among the known risk factors for AF, the most frequent were diabetes (16%, n=111) and previous heart failure (22%, n=111). Regarding disease-specific factors contributing to the pathophysiology of AF, cardiac iron overload, defined as at least one between T2*&lt;20 ms and serum ferritin&gt;2500 ng/ml, was present in half of the patients (48.7%, n=76) at any time before AF and in approximately one-third (29%, n=93) at the time of the first event. Thirty-eight patients did not show cardiac iron overload before or at the time of the first AF episode. Most subjects had left atrial dilatation (58.1%), which can result from chronically increased cardiac output due to anemia.

In most patients (87%), a rhythm control strategy was chosen at any time. Amiodarone was the most widely used drug. Transcatheter ablation was performed in 29 patients (22%), with a total of 39 procedures, and 20 (77%) patients reported improvement in symptoms after the last ablation.

CHA 2DS 2-VASc score at the first AF episode detected a low risk of thromboembolism in 66 (50.8%) patients and a high risk in 19 (14.6%). However, 72 patients, including 40 low-risk subjects, initiated anticoagulation after the first episode. Four patients had a hemorrhagic event (3.1%), but only one had major bleeding during anticoagulant therapy without significant sequelae. Interestingly, management was heterogenous between different centers for both transcatheter ablation use and anticoagulation strategy.

The prevalence of stroke in TDT AF patients was 5%, rising to 7.6% when also considering transient ischemic attacks. Compared to the literature, this prevalence is at least 10-fold higher than the general TDT population. Of note, splenectomy, a well-known risk factor for thrombosis, was present in all patients with stroke at the time of the event.

In conclusion, AF represents significant morbidity in adult TDT, and its management is heterogeneous. It generally occurs at a younger age than the general population, and iron overload and atrial dilatation play a central role in its genesis. For symptomatic patients, we propose a rhythm control strategy to improve their quality of life, among which ablation could be the best option. Moreover, because stroke represents a major and frequent complication in TDT patients with AF, early detection of AF and prompt initiation of anticoagulant therapy, irrespective of CHA 2DS 2-VASc, which does not capture potential disease-specific risk factors, including splenectomy, should be considered. Further studies to support our approach are needed.