Paulamy Ganguly

Introduction: The etiology of takotsubo cardiomyopathy (TCM) is poorly understood, yet the increased concentration of catecholamines is most often implicated in disease pathophysiology⁽¹⁾. Under stressful conditions, influx of catecholamines stimulates B-adrenergic receptors which leads to cardiomyocyte necrosis and toxicity⁽¹⁾. Patients with TCM present with chest pain, dyspnea or syncope, elevated B-natriuretic peptide and troponin-I, ST segment elevation and other imaging findings^(1,2). This abstract reviews current research aimed at understanding the mechanism of disease pathology and potential avenues for new therapies. Methods: Three research papers were reviewed to develop an understanding of genetic contribution, disease modeling and therapies. First, Mattsson et al (2018) attempted to establish a difference between β1-adrenergic receptor (ADRB1) in TCM and non-TCM patients (n=258 and n=407 respectively)⁽¹⁰⁾. Secondly, Madias et al (2021) highlights a new indication for insulin after observing an increase in cardiac contractility, cardiac output and glucose uptake in TCM patients⁽³⁾. Lastly, Liao et al (2022) conducted a study which utilized isoproterenol (ISO) to induce TCM-like cardiomyopathy through macrophage infiltration and cardiomyocyte dysfunction visualized by H&E staining and TUNEL staining which can effectively model TCM in vitro⁽⁶⁾. Results: Madias et al demonstrated hemodynamic changes observed in two patients treated with high doses of insulin, which showed an increase in cardiac output (CO) after an insulin bolus, and a decline following the withdrawal of insulin in consecutive instances⁽³⁾. ISO-induced TCM demonstrated fibrosis in mice cardiomyocytes and these fibrotic regions also demonstrated positive TUNEL DNA fragmentation⁽⁶⁾. Genotypic differences for ADRB1 did not differ between TCM and non-TCM groups⁽¹⁰⁾. A Chi-Square Test of Independence was performed to assess the relationship between TCM and presence of one rare homozygous allele, with no observed significance difference X² (1, N= 665)=1.57, p=.46. Conclusion: The factors influencing TCM development include age, sex, history of mood disorders and comorbidies including HTN, HLD, etc but at this time, the contribution of genetics in disease pathophysiology is not conclusive. Researchers have found ways to model and mimic the cardiomyocyte damage seen in TCM using exogenous chemicals, and also discovered new indications for currently existing drugs: insulin can be used to improve CO⁽³⁾ and oncology medications to revert cardiomyocyte damage⁽⁶⁾. However, apart from these findings, the rate of novel discoveries has stagnated over the years despite the severe consequences of TCM and a demonstrated lack of understanding of the pathophysiology and etiology of TCM.

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