Clinical characteristics and outcome of emotional trigger subtypes in takotsubo syndrome

Background takotsubo syndrome (TTS) is an acute heart failure phenotype frequently preceded by a stressful trigger and associated with abnormal activation of cerebral areas including the amygdala. Though emotional triggers have been robustly associated with favourable outcomes in TTS, little is known regarding these triggers subtypes. Purpose to evaluate clinical characteristics and outcome of emotionally triggered TTS patients according to the event subtype. Methods a retrospective analysis on a multicenter TTS registry was conducted. After excluding patients without an emotional trigger nor clear description of the triggering event, n=169 patients were included in the analysis. Based on previous studies in the literature [1], emotional triggers were categorized into three groups: A) Grief or Loss (n=28); B) Fear or Anxiety (n=68); C) Rage or Conflict (n=73). Echocardiography was performed on admission. Cardiac magnetic resonance (CMR) imaging was performed during in-hospital stay in a subset of n=54 patients. Univariable and multivariable logistic regression was conducted to identify factors independently associated with emotional trigger subtypes. Kaplan-Meier curves were used to assess long-term outcomes. Results mean age of the study cohort was 72±10 years, 6% male, apical contraction pattern in 79%. Age was similar between groups. Male sex prevalence was 0%, 3% and 11% in group A, B and C respectively (p=0.024). Some comorbidities were more frequent in group B (cancer: 7%, 19%, 7% respectively, p=0.005; autoimmune disease: 4%; 12%; 2% respectively, p=0.207). Focal contraction patterns were uncommon (n=5) but all concentrated in group B. No significant differences between groups were noted regarding other echocardiographic and CMR characteristics as well as in-hospital outcomes. Multivariable logistic regression analysis identified cancer [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.06-8.21] and angina [OR 0.2, 95% CI 0.11-0.49, p<0.001] as independent factors associated with group B, and male sex [OR 6.6, 95% CI 1.21-35.9; p=0.025] and angina [OR 3.8, 95% CI 1.64-9.16; p=0.002] with group C. With a median follow-up of 670 days, Kaplan-Meier curves showed similar prognosis across groups (log-rank p= 0.568). Conclusion Contrary to common belief, grief or loss is not the main emotional trigger in TTS. Clinical characteristics differ between trigger subtypes cohorts including factors that may hinder a timely diagnosis. Sex differences in emotional trigger subtypes suggest potential cultural or biological variations in the brain-heart axis activation in TTS, warranting further prospective and multidisciplinary investigation. Although emotional trigger subtype does not appear to impact the severity of myocardial involvement nor in-hospital or long-term outcomes, our findings highlight critical elements for future research into the brain-heart axis in TTS patients.