Takotsubo Syndrome Using the InterTAK Criteria: Insights from Inter- TAK-Defined Patients (A Systematic Review)

INTRODUCTION: To synthesize contemporary evidence on epidemiology, triggers and risk factors, pathophysiology, clinical presentation, diagnosis, management patterns, and outcomes in Takotsubo Syndrome (TTS) restricted to studies using the International Takotsubo (InterTAK) Diagnostic Criteria. METHODS: A PRISMA‑guided systematic review of major bibliographic databases was performed, limited to studies published between 2019 and October 2024. Pre‑specified criteria were: Inter- TAK diagnosis, English language, and minimum sample size ≥ 30. No meta‑analysis was initially planned due to heterogeneity; however, to report more precisely on in-hospital mortality, we focused on a minimal meta-analysis based on high-quality publications. RESULTS: Across studies, approximately 78% of participants were female, with reported mean ages ranging from 54 to 79 years. Physical triggers were most frequent and associated with higher rates of cardiogenic shock and mortality. Emotional triggers had the most favourable short-term outcomes, while unknown-trigger cases more often presented with arrhythmia. T-wave inversion and ST-segment changes were the most common Electrocardiogram (ECG) findings. Several noninvasive diagnostic tools showed high accuracy in differentiating TTS from ACS. Management was largely supportive and heart-failure/ACS-oriented. In-hospital mortality ranged from 5% in general cardiology series to > 60% in ICU cohorts. Early ventricular arrhythmias occurred predominantly within 48 hours and were predicted by QTc. Long-term follow-up revealed variable mortality rates but frequent persistent subclinical dysfunction despite recovery of Left Ventricular Ejection Fraction (LVEF). Persistent Left Ventricular Global Longitudinal Strain (LV-GLS) impairment at 3-6 months was associated with adverse long-term outcomes. DISCUSSION: This review exclusively focused on studies applying the InterTAK Diagnostic Criteria. A major strength of this review is its diagnostic consistency. The epidemiological profile of TTS in the included studies closely aligns with prior large-scale registry data, particularly the InterTAK Registry (2), which demonstrated a predominance among postmenopausal women and a mean presentation age in the late sixties. This diversity in presentation underscores the importance of early, structured assessment whenever TTS is suspected. Bedside clinical scores may improve early triage of suspected TTS, particularly when angiography is delayed or inconclusive. CONCLUSION: TTS is a heterogeneous condition with diverse presentations, evolving diagnostic tools, and important prognostic implications. Large, prospective studies are needed to refine diagnosis, validate prognostic tools, and develop effective targeted therapies to improve outcomes.