Exploring the Role of Psychological Stress in TAKOTSUBO CARDIOMYOPATHY: The 'Broken Heart' Syndrome

Takotsubo syndrome (TTS), or 'broken heart' syndrome, is an acute, reversible cardiomyopathy classically linked to emotional stress. Although physiological mechanisms have been extensively described, the psychological stress profile of patients with TTS remains incompletely synthesised. This study aimed to systematically review and meta-analyse observational studies examining psychological stress-related factors in patients with TTS compared with cardiac and non-cardiac control groups. We searched PubMed/MEDLINE, Embase, PsycINFO, Scopus, and Web of Science from 1 January 2011 to 31 March 2024 for observational studies of adults with TTS that used validated psychological assessments and included a cardiac or non-cardiac comparison group. Two reviewers independently screened studies, extracted data, and assessed risk of bias with the Newcastle-Ottawa Scale. Random-effects meta-analysis pooled odds ratios (ORs) for study-defined binary psychological endpoints, and comparator-group subgroup analyses were treated as main analyses. Sixteen studies met the inclusion criteria, comprising 1133 patients with TTS and 1396 controls, including 1061 cardiac controls and 335 non-cardiac controls. Across studies, patients with TTS showed higher rates of acute emotional triggers, lifetime mood and anxiety disorders, trauma history, maladaptive personality traits (e.g., neuroticism and Type D personality), and broader psychological distress, including posttraumatic stress symptoms, sexual distress, and reduced quality of life. The pooled OR for overall psychological morbidity/stress exposure was 6.50 (95% CI: 3.14-13.49), with substantial heterogeneity (I² = 84.1%). Comparator-category subgroup analyses showed larger effects against acute coronary syndrome/acute myocardial infarction controls than against healthy volunteers alone. TTS is strongly associated with both acute emotional stressors and chronic psychological vulnerability, supporting models that conceptualise the syndrome as an extreme stress response of the cardiovascular system. These findings reinforce the value of routine psychosocial assessment and stress-focused interventions in the care of patients with TTS.