AbstractAlthough patients with sickle cell disease (SCD) carry both significant left atrial (LA) remodeling and an increased risk for stroke, the prevalence of atrial arrhythmia (AA) has never been evaluated prospectively. This study aimed to investigate the prevalence and predictors of AA in homozygous SCD (sickle cell anemia [SCA]). From 2019 to 2022, 130 patients with SCA were referred to the physiology department to specifically analyze cardiac function and were prospectively included in the DREPACOEUR registry. They underwent 24-hour electrocardiogram monitoring (ECG-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary end point was the occurrence of AA, defined as the presence of excessive supraventricular ectopic activity during the ECG-Holter (ie, >720 premature atrial contractions [PACs] or any run with ≥20 PACs), recent history of paroxysmal atrial fibrillation (AF), or persistent AF. The mean patient age was 45 ± 12 years, and 48% were male. Overall, AA was found in 34 patients (26%). Age (52 ± 9 vs 42 ± 12 years; P = .002), LA dilation (LA volume indexed to body surface area [LAVi]; 71 ± 24 vs 52 ± 14 mL/m2; P < .001), and a history of stroke without underlying cerebral vasculopathy or other defined cause (26% vs 5%; P = .009; odds ratio, 6.6; 95% confidence interval, 1.4-30.3) were independently associated with AA. Age and LAVi correlated with PAC load per 24 hours measured during ECG-Holter (R = 0.56 and 0.33, respectively; P < .001) and an age >47 years or an LAVi >55 mL/m2 could predict AA with a positive predictive value of 33% and a negative predictive value of 92%. AAs are frequent in patients with SCA and increase with age and LA remodeling and lead to a major additional risk factor for ischemic stroke. This study provides arguments and means for early screening for AA, thereby potentially preventing cerebral complications.