Elucidating physiologic influences of sleep-related breathing and architectural disruption in Takotsubo syndrome.

Authors

Sepideh Khazaie, Michael D Faulx, James F Bena, Shannon L Morrison, Alex Milinovich, Megan Sheehan, Lu Wang, Reena Mehra

Published in

Heart and vessels. Jul 19, 2026. Epub Jul 19, 2026.

Abstract

Takotsubo syndrome (TS), an acute stress-induced cardiomyopathy driven by catecholamine excess, shares pathophysiological features with sleep disordered breathing (SDB), yet this relationship remains unexplored. We hypothesize that SDB and sleep disruption influences TS risk and severity.
We leveraged data from the Cleveland Clinic sleep cohort (1999-2021) including patients with proven TS and matched controls (1:5 ratio by age, sex, body mass index (BMI), and study year). Logistic regression models were used to assess odds of TS associated with SDB biomarkers, i.e., apnea-hypopnea index (AHI; evaluated at thresholds ≥ 5, ≥15, and ≥ 30), hypoxia (percentage of sleep time with SaO₂ <90%) and the arousal index, while adjusting for age, sex, BMI, comorbidities (hypertension, diabetes, and hyperlipidemia), and overall cardiovascular medication use. Spearman correlations were used to examine relationships between sleep measures and left ventricular ejection fraction (LVEF) in TS patients.
S cases (n = 84; mean age 64.1 ± 11.4 years, 86.9% female, BMI 30.9 ± 7.7 kg/m²) had higher comorbidity (e.g., 45.2% vs. 10.1% coronary artery disease, p < 0.001) and lower PAP use (17.9% vs. 43.0%, p < 0.001) compared to matched controls (n = 414). Mild OSA (AHI 5-<15) was associated with reduced odds of TS in unadjusted models (OR = 0.49, 95% CI 0.25-0.94, p = 0.032) and remained significant after adjustment for age, sex, BMI, comorbidities, and overall cardiovascular medication use (OR = 0.48, 95% CI 0.24-0.96, p = 0.037). In the subgroup analysis of patients with pre-TS sleep studies (n = 36), a stronger association was observed for overall OSA (AHI ≥ 5) (OR = 0.34, 95% CI 0.13-0.91, p = 0.031). Arousal index correlated with lower LVEF in pre-TS cases (rho = - 0.40, p = 0.024). Moderate/severe OSA and hypoxia showed no significant association with TS.
Mild OSA may be protective in TS, possibly via hypoxic preconditioning, while sleep fragmentation is associated with greater cardiac dysfunction. This first study of SDB in TS highlights a novel sleep-cardiac interplay, warranting further investigation.

PMID:
42472739
Bibliographic data and abstract were imported from PubMed on 20 Jul 2026.

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