Takotsubo cardiomyopathy: Advances in pathophysiology, diagnostic biomarkers, genetic insights, multisystemic involvement, treatment updates & multidisciplinary interventions

Abstract

Background: Takotsubo cardiomyopathy (TTC) is an acute, reversible cardiac syndrome triggered by physical or emotional stress, involving complex multi-system interactions, with unclear mechanisms and variable prognosis across patient subgroups.

Objectives: To synthesize current evidence on comorbidities, biomarkers, genetic predispositions, prognostic factors, and management strategies in TTC, highlighting clinical implications and research gaps for improved diagnosis, prevention, and patient outcomes.

Methods: A systematic review was conducted on studies published between January 2015 and July 2025. Search was performed across Embase, PubMed, Web of Science, Scopus and Google Scholar using predefined MeSH terms and keywords. Twenty-five studies were included in this review. Quality assessment was conducted using the Newcastle-Ottawa Scale.

Results: TTC was associated with psychiatric disorders, malignancies, endocrine and inflammatory conditions, and neurological insults. Apical ballooning morphology predicted worse outcomes. Biomarkers (NT-proBNP/TnI) and echocardiography improved diagnostic accuracy. Adrenergic receptor polymorphisms (GRK5 L41Q, α2CDel322-325) increased susceptibility in select populations, though genetic findings were inconsistent. Psychological support and beta-blockers improved recovery, while machine learning models enhanced prognostic prediction. ICU-based early echocardiographic screening identified high-risk patients. Multi-disciplinary approaches integrating cardiovascular, psychological, and genetic considerations yielded better patient outcomes. Evidence was limited by heterogeneity, small genetic cohorts, and inconsistent follow-up durations, highlighting the need for standardized diagnostic criteria and prospective, multicenter studies.

Conclusion: TTC is a multifactorial syndrome requiring integrated diagnostic, therapeutic, and preventive strategies. Early detection, comorbidity management, and personalized care improve prognosis. Standardized research is needed to refine understanding and optimize management.

Keywords: Adrenergic receptors; Biomarkers; Comorbidities; Echocardiography; Genetic predisposition; Machine learning; Prognosis; Takotsubo cardiomyopathy.