Atrial fibrillation (AF) is showing up with increasing frequency in older adults with transfusion-dependent β-thalassemia, and the pattern looks different from what cardiologists are used to seeing in the general population. The FATHAL study, a retrospective analysis spanning nine Italian centers, set out to define just how common AF is in this setting and how it is being treated. As patients with transfusion-dependent β-thalassemia live longer, the cardiac picture has changed. Overt heart failure is no longer the dominant late complication. Instead, atrial arrhythmias are moving to the foreground.
The cohort included 1,389 adults in regular follow-up through the end of 2023. Among them, 188 had experienced at least one episode of AF, for an overall prevalence of 11.9%. Age made a clear difference. AF was present in nearly one-third of patients older than 66 and in about 20% of those older than 50. That contrasts sharply with population estimates, where AF generally affects 2% to 4% of adults overall and roughly 5% to 6% of those older than 65. Just as striking, the mean age at first AF episode in this thalassemia cohort was 40.3 years. In other words, arrhythmia is arriving decades earlier than expected.
Men accounted for 61% of AF cases. Splenectomy was common, reported in 73%. Most patients had β-thalassemia major, although a quarter had intermedia that later became transfusion dependent. At data cut-off, the mean age of survivors was 51.9 years. Twenty-three deaths were recorded during follow-up, and about two-thirds were attributed to cardiac causes.
Comorbid conditions were frequent and, in many cases, longstanding. One quarter of patients had a history of heart failure at the time of their first AF episode. Prior supraventricular arrhythmias had been documented in 15.6%. Diabetes and hypothyroidism were both prevalent, consistent with chronic iron-related endocrine injury. Diabetes rates exceeded those reported in the general Italian population. Hypertension increased over time, rising from 2.9% earlier in the disease course to 16.4% later on. Clinically meaningful valvular disease also became more common as the cohort aged.
Iron overload was clearly part of the story, but not the entire explanation. Nearly half of patients had documented cardiac iron overload before AF developed. At the time of the first episode, roughly one-third still showed evidence of cardiac iron, yet many had normal T2* measurements. Iron overload was more frequent in patients with thalassemia major than intermedia, but AF still occurred in patients without active cardiac iron deposition. That pattern suggests residual atrial injury or remodeling that is not fully captured by ventricular T2* imaging.
Echocardiographic data at first AF episode support that interpretation. Left atrial enlargement was present in 65.2% of patients. By contrast, only 6.6% had significant valvular disease and 6.7% had a left ventricular ejection fraction below 40%. Severe systolic dysfunction was uncommon. Chronic anemia, high-output physiology, and structural atrial changes likely form the substrate.
Clinically, AF was paroxysmal in 76.1% and symptomatic in most cases, usually with palpitations. Hemodynamic instability occurred in about 15%. Rhythm control was attempted in the majority of patients, often with amiodarone. After a median of nine years, nearly 80% were in sinus rhythm.
Catheter ablation was performed in 26.6% of patients, at a mean age younger than 44. No procedural complications were reported. One-third achieved sustained rhythm control without recurrence, and most reported symptomatic improvement. Notably, the first ablation occurred more than seven years after AF onset on average, suggesting delayed referral.
Thromboembolic events were not rare. Seventeen patients experienced arterial events, including cerebral ischemia in 7.9% and stroke in 5.5%, at a median age of 37. Although most patients received anticoagulation at some point, events still occurred during therapy. Many had low CHA₂DS₂-VASc scores at first presentation, yet thromboembolism was observed across risk categories. Nearly all patients with events had undergone splenectomy.
Taken together, the findings suggest that AF in β-TDT behaves differently from AF in the general population. Earlier onset, substantial thromboembolic risk, and the potential contribution of splenectomy and chronic iron injury raise practical questions about how best to stratify risk and intervene. Standard algorithms may not be enough for this group.