Meteorological impact on ventricular arrhythmias in sickle cell disease

Abstract Background: Patients with sickle cell disease (SCD) are known to have a heightened burden of ventricular ectopy, yet the contribution of environmental stressors—particularly temperature and rainfall—remains poorly understood. Given the physiological vulnerability of SCD patients to cold exposure and vascular stress, we hypothesized that meteorological conditions may contribute to arrhythmic risk through intricate environmental interactions, reflecting the complex interplay between physiology and climate. Aim: To investigate the relationship between weather patterns and ventricular arrhythmias in adults with SCD undergoing 24-hour Holter ECG monitoring. Method: Between January 2019 and December 2023, consecutive adults with homozygous SCD were prospectively enrolled in the DREPACOEUR registry, designed to characterize cardiac structure and function in SCD. All participants underwent a comprehensive cardiovascular evaluation at steady state in a day-hospital setting, including clinical examination, cardiac imaging, 24-hour rhythm monitoring, and laboratory analyses. Meteorological data corresponding to the day of Holter recording were retrieved from public datasets. Climate variables were modeled using multivariate polynomial regression, generalized additive models (GAMs), and k-means clustering. Season and semester were included as categorical variables. Group comparisons were conducted using ANOVA and Kruskal-Wallis tests, as appropriate. Results: A total of 150 adults with homozygous SCD were included (median age 32 years, IQR: 24–41; 53% female). A high burden of premature ventricular contractions (PVCs >500/24h) was observed in 21% of patients. PVC load was significantly higher during the first semester of the year (p < 0.01), particularly in winter compared to summer (p = 0.03). First-semester evaluation was independently associated with PVC burden in multivariate analysis (OR = 2.9, 95% CI [1.1–8.1], p = 0.039), whereas hemoglobin level and markers of hemolysis were not. A U-shaped association was found between ambient temperature and PVC load, with the highest arrhythmic burden in cold and dry conditions. Discriminant analysis confirmed distinct clustering of climate profiles, with clear separation of PVC phenotypes based on mean temperature and rainfall. Interestingly, rainfall appeared to attenuate the arrhythmogenic impact of both low and high temperatures, suggesting a protective behavioral or physiological response. This complex meteorological interaction was further illustrated using a bivariate predictive map, demonstrating increased PVC risk in cold dry air, which was notably mitigated when rainfall co-occurred. Conclusion: In SCD, ventricular arrhythmias appear to be modulated by environmental conditions in a complex and seasonal manner. Cold and dry weather markedly increases PVC burden, while rainfall may exert a moderating influence—possibly through behavioral adaptation or physiological buffering. These findings highlight the importance of integrating environmental awareness into arrhythmic risk prevention strategies in SCD.