Novel predictors of major adverse cardiovascular events in patients with Takotsubo cardiomyopathy: a contemporary analysis

Background: Takotsubo cardiomyopathy (TCM) is considered a reversible condition; however, it can predispose patients to significant long-term morbidity and mortality. As there is a paucity of literature regarding the long-term clinical outcomes in patients with TCM, we performed a systematic review and meta-analysis to evaluate the clinical, biochemical and imaging factors that are associated with major adverse cardiovascular events (MACE) in these patients. Method: A systematic search of databases following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines was utilised to identify studies that reported MACE and mortality in patients with TCM (PROSPERO CRD42025648547). Variable data were extracted and meta-analysed using random-effect modelling. Direct parameter comparisons were conducted using odds ratios (ORs) and standardised mean differences, while a pooled hazard ratio (HR) was meta-analysed for mortality. A two-tailed P-value of <0.05 was deemed significant. Results: Of 320 studies screened, 19 met our inclusion criteria, comprising a total of 6443 patients. Predictors of MACE included a presentation with dyspnoea (OR, 1.41 (95% confidence interval (CI), 1.037–1.907), P = 0.028), Killip-Kimball classification of heart failure >1 (OR, 2.216 (95% CI, 1.673–2.936), P < 0.001) and secondary TCM (OR, 1.538 (95% CI, 1.051–2.251), P = 0.027). Right ventricular involvement (HR, 1.90 (95% CI, 1.14–3.16), P = 0.01) was identified as a predictor of mortality. Physical stressors and diabetes were predictors of both MACE and mortality (P < 0.05). Killip–Kimball class >1 was significantly stronger than dyspnoea (P 0.033 for interaction), while other novel predictors including secondary TCM, diabetes, physical stressors and right ventricular involvement demonstrated comparable effect sizes. Conclusion: This study outlines several novel risk factors for poor long-term outcomes in patients with TCM. Identification of these high-risk subpopulations early may allow for more intensive therapy and follow-up.