Chronobiological variation in takotsubo syndrome: an updated systematic review and meta-analysis

Takotsubo syndrome (TTS) might exhibit particular chronobiological patterns in its onset, characterized by variations according to time of the day, day of the week, and month of the year. The aim of this study was to fully explore the temporal patterns (circadian, weekly and seasonal) in the onset of TTS. A systematic review and meta-analysis of literature were conducted for studies (2006-2024) reporting the temporal patterns (circadian, weekly and/or seasonal) in the onset of TTS. Among the 4257 studies retrieved, 20 (including 64,567 subjects) fulfilled all eligibility criteria. Data were aggregated used random effects model as pooled risk ratio and the attributable risk (AR). The proportion analysis (including 8 studies; n=853) showed a decreasing pattern of the pooled rates of TTS shifting from the morning to the night (pooled TTS rates: 34.0%; 32.1%; 21.7%; 12.7% in the morning, afternoon, evening and night, respectively). The same pattern was observed stratifying by type of preceding stressful factor or event, considering physical stressors (pooled rates in the morning and night: 37.6% and 9.8%, respectively), and also in case no event could be identified. The pooled rates of TTS onset peaked on Monday and Tuesday (17.3% and 18.4% respectively), then declined during the week, reaching the lowest rates on Friday and Saturday (10.6% and 10.8%, respectively), with no sex differences. TTS onset reached the highest values on summer, and the lowest in winter (27.9% versus 21.7% in summer and winter, respectively). The TTS morning peak based analyses (∼33% of all the registered events) account for a RR of 1.46 (95% CI: 1.38-1.54), the week-based for a RR of 1.26 (1.16-1.35), the season-based for a RR of 1.04 (1.04-1.05). TTS onset exhibits specific chronobiological patterns, characterized by a peak during the morning hours, and on Monday and Tuesday. Differing from other cardiovascular emergencies TTS was more frequent during summer. Further studies are needed to fully understand the underlying pathophysiological mechanisms in order to tailor relative management and preventive strategies.