Yastremska I. Clinical features and treatment optimization in acute myocardial infarction with ST segment elevation in patients with comorbid metabolic syndrome

The thesis work is devoted to optimization of treatment program and reducing the rates of life-threatening complications at an early stage of myocardial infarction which has developed in the setting of metabolic syndrome through correction of metabolic, hemodynamic and endothelial disorders by the use of L-arginine/L-carnitine and SGLT2 inhibitor dapagliflozin. The pathogenetic mechanisms underlying the mutually aggravating course of myocardial infarction combined with MS have been identified; the study has demonstrated the role of insulin resistance in impaired activity of free-radical lipid oxidation, endothelial dysfunction and excessive activation of systemic inflammatory response, which have been associated with clinical, structural and functional, and laboratory clinical features of acute coronary syndrome (myocardial infarction) in the setting of metabolic syndrome. The study has clarified that the distinctive feature in the course of STEMI combined with MS was the significantly higher proportion of subjects with atypical clinical manifestations of MI (the absence or atypical localization/irradiation of pain, the predominance of signs of acute heart failure such as dyspnoea/shortness of breath), which could impede timely diagnosis and delay treatment. Such comorbid patients were noted to have significantly more frequent multi-vascular and hemodynamically significant lesions of coronary arteries, which was accompanied by significantly more frequent development of such life-threatening complications as acute class ІІІ-ІV heart failure, critical cardiac rhythm and conduction disorders, acute LV aneurysm, early post-infarction angina and epistenocarditic pericarditis. It has been established that, compared to patients with isolated ACS, patients with ACS (STEMI) combined with MS and insulin resistance had significantly greater increases in LV myocardial mass index and LV volume due to LV hypertrophy and remodeling. As a consequence of these processes, there is a significant impairment of systolic and diastolic cardiac function, and a significantly more frequent (twofold difference) development of Killip class III-IV AHF. The identified robust and direct correlation between the AHF class and cardiohemodynamic parameters (r=0.383–0.764) supports the rationale for prescribing cardiocytoprotective therapy. This study is to demonstrate that the high insulin resistance index (> 2.7) in patients with MS + STEMI is associated with more pronounced manifestations of such metabolic disorders as atherogenic dyslipidemia (the atherogenicity coefficient increases to 4.0), predominance of lipid peroxidation over the protective capacity of antioxidant enzyme systems, endothelial dysfunction and activation of systemic inflammatory response. As an ultimate result, this leads to enhanced abnormal processes in the heart and its functional impairment. This study is to demonstrate that enhancement of the treatment program for patients with ACS (STEMI) combined with MS and insulin resistance with the SGLT2 inhibitor dapagliflozin and L-arginine/L-carnitine combination ensured an improvement of clinical course of concomitant disease and a significant reduction in the frequency of life-threatening complications of ACS through reducing insulin resistance, compensation of carbohydrate metabolism and the cardioprotective effects of drugs. This was associated with restored endothelial function of blood vessels, improved cardiac contractility, reduced manifestations of systemic inflammatory response and improved functional capacity of antioxidant defense systems of the body.