Takotsubo cardiomyopathy - differentiation from acute coronary syndrome by electrocardiography and biochemistry

Takotsubo cardiomyopathy (TTC) is an acute cardiac condition resembling in symptoms acute coronary syndrome (ACS), but without obstructive coronary artery disease. TTC develops almost solely in post-menopausal women and usually after preceding stress. Of all patients with ACS symptoms, TTC incidence is 2%. Due to similar symptoms and findings, differential diagnosis requires coronary angiography (CAG). The pathophysiology of TTC is unknown. Even though the accumulated evidence suggests a causative role for a catecholamine surge, other theories exist. Aborted myocardial infarction (MI) produces similar electrocardiography (ECG) and biochemical findings as in TTC. In such cases, because of non-stenotic coronary artery plaques, a dissolved coronary thrombus might show no any signs in the CAG, which could lead to an assumption of non-atherothrombotic etiology for the heart attack. In ACS, altered levels of proteolytic enzyme called matrix metalloproteinase 8 (MMP-8), and its inhibitor, the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), associate to plaque rupture. Their direct comparison between ACS and TTC remains unknown. The purpose of this thesis is to test whether either of two non-invasive methods: the ECG (I) or MMP-8 and TIMP-1 (III), could differentiate TTC from ACS. We also set out to find whether, after all, what is responsible for the TTC is transient thrombosis in the coronary circulation (II). Both our prospective and retrospective collection of patients resulted in 92 TTC cases. The demographics of our material were similar to those of other TTC reports worldwide. In the ECG study (I), a review and comparison of 57 TTC and ACS acute ECGs resulted in criteria differentiating the two with 63% sensitivity and 93% specificity. In cases of suspected ST-elevation myocardial infarction, such accuracy is insufficient for a decision against coronary intervention. Blood samples from 45 TTC patients and matching numbers of ACS patients and controls were analyzed for coagulation markers. Despite the similar acute-phase reaction in TTC and ACS patients, the TTC d-dimer levels matched those of controls, and were lower and less frequently above reference level than with those in ACS. The blood samples were further analyzed for MMP-8 and TIMP-1 levels showing, on admission, better differentiation between TTC and ACS by TIMP-1 than by troponin T (TnT). In TTC, low ejection fraction (EF) correlated with low MMP-8/TIMP-1 ratio. In conclusion, ECG lacked the ability to differentiate TTC from ACS that would have allowed avoidance of invasive diagnostics. Secondly, the coagulation results supported catecholamine and argued against the thrombosis theory. Finally, TIMP-1 emerged as a potential future biomarker in differentiation between ACS and TTC. Furthermore, in some TTC patients MMP-8 and TIMP-1 levels may explain more severe left-ventricle (LV) impairment.