What is the clinical evidence from this study?

Study design: Case-Control. Population: Takotsubo syndrome (n=498). Intervention: Mild obstructive sleep apnea (AHI 5-<15) vs. Matched controls. Primary outcome: Odds of Takotsubo syndrome (OR 0.48, 95% CI 0.24-0.96, p=0.037).

What does this research mean for the field?

Mild obstructive sleep apnea is associated with a reduced risk of Takotsubo syndrome, while sleep fragmentation correlates with greater cardiac dysfunction in affected patients. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

What question did this study set out to answer?

This study aims to explore the relationship between sleep disordered breathing and its influence on the risk and severity of Takotsubo syndrome.

July 21, 2026Heart and Vessels0 citationsOpen Access

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

Q: What are the key findings of this study?

Mild obstructive sleep apnea was associated with significantly reduced odds of Takotsubo syndrome (OR 0.48; 95% CI 0.24-0.96; p=0.037).

Q: What does this research mean for the field?

Mild obstructive sleep apnea is associated with a reduced risk of Takotsubo syndrome, while sleep fragmentation correlates with greater cardiac dysfunction in affected patients. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

Q: What question did this study set out to answer?

This study aims to explore the relationship between sleep disordered breathing and its influence on the risk and severity of Takotsubo syndrome.

SKSepideh KhazaieCleveland Clinic Lerner College of Medicine MFMichael FaulxCleveland Clinic JBJames F. BenaCleveland Clinic

Key Result

Mild obstructive sleep apnea was associated with significantly reduced odds of Takotsubo syndrome (OR 0.48; 95% CI 0.24-0.96; p=0.037).

Key Points

This study aims to explore the relationship between sleep disordered breathing and its influence on the risk and severity of Takotsubo syndrome.
Analyzed data from the Cleveland Clinic sleep cohort (1999–2021) with patients diagnosed with Takotsubo syndrome and matched controls.
Utilized logistic regression to assess odds of Takotsubo syndrome in relation to sleep disordered breathing biomarkers.
Examined correlations between sleep measures and left ventricular ejection fraction in Takotsubo syndrome patients.
Mild obstructive sleep apnea was associated with reduced odds of Takotsubo syndrome (OR = 0.48, 95% CI 0.24–0.96, p = 0.037).
Arousal index showed a negative correlation with left ventricular ejection fraction (rho = −0.40, p = 0.024).
No significant association found between moderate/severe obstructive sleep apnea, hypoxia, and Takotsubo syndrome.

Study Design

Type

Case-Control (n=498)

Structured PICO

Does sleep-disordered breathing influence the risk and severity of Takotsubo syndrome?

Population

498 patients (84 with Takotsubo syndrome and 414 matched controls) from a sleep cohort evaluated for the association between sleep-disordered breathing and Takotsubo syndrome.

Exposure

Sleep-disordered breathing (SDB) and sleep disruption, assessed by apnea-hypopnea index (AHI), hypoxia, and arousal index.

Comparator

Matched controls without Takotsubo syndrome (matched 1:5 by age, sex, BMI, and study year).

Outcome

Odds of Takotsubo syndrome associated with SDB biomarkers.

Mild obstructive sleep apnea may be protective against Takotsubo syndrome, potentially through hypoxic preconditioning, whereas sleep fragmentation is associated with worse cardiac dysfunction.

Main Result

Odds Ratio: 0.48 (95% CI 0.24–0.96)

p-value: p=0.037

Abstract

Abstract Background: 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. Methods: 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 SaO 2 <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. Results: S cases ( n = 84; mean age 64.1 ± 11.4 years, 86.9% female, BMI 30.9 ± 7.7 kg/m 2 ) 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. Conclusions: 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.

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