Markers of myocodial fibrosis in acute myocardial infarction

Funding Acknowledgements Type of funding sources: None. One of the leading mechanisms in the healing process of acute myocardial infarction (AMI) is damage and loss of extracellular matrix, which plays a leading role in the pathogenesis of LV myocardial remodeling. Tissue inhibitor of matrix metalloprotease-1 is a protein that is a natural inhibitor of metalloproteases, forms complexes with MMP-1 and other metalloproteases (they destroy components of the extracellular matrix of the heart), irreversibly inhibiting their activity. Bayes-Genis A. et al presented histological data on the expression in ruptured and eroded plaques of plasma protein A (PAPP-A), metalloproteinase and insulin-like growth factor-1 detected during pregnancy. Myocardial formation of aldosterone and angiotensin II (as a result of activation of the renin-angiotensin-aldosterone system, including the tissue component) after acute myocardial infarction stimulates the formation of collagen and fibrous tissue in the myocardium with further changes in the structure and geometric characteristics of the left ventricle. Purpose of the study. To study the markers of interstitial myocardial fibrosis in the acute stage of myocardial infarction and assess the dynamics of these indicators in patients after 2.5-3 weeks of inpatient treatment. Methods. The study included 31 patients with myocardial infarction with ST segment elevation. The control groups consisted of 20 apparently healthy individuals. During the study, serum parameters of tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1 and aldosterone were measured on days 1-3 after AMI and after 2.5-3 weeks of inpatient treatment. Results. The level of TIMMP-1 in patients with acute MI was 418.19 ± 103.77 ng / ml and was statistically significantly higher than in practically healthy individuals - 103.44 ± 7.06 ng / ml (p <0.0001) , The level of TIMMP-1 in patients with AMI after 3 weeks, against the background of ongoing therapy, was 366.70 ± 93.34 ng / ml, and the decrease in TIMMP-1, compared with the initial value in the acute stage, had a statistical significance (p = 0.046). The level of aldosterone in acute myocardial infarction was 165.12 ± 32.67 pg / ml and was statistically significantly higher (p <0.0001) than in the control group. In patients with myocardial infarction who are hospitalized, for 2.5-3 weeks, there is a statistically significant (p = 0.003) decrease in the concentration of aldosterone in blood plasma by 15.1% from 165.12 ± 32.67 pg / ml to 140.24 ± 22.78 pg / ml. Conclusions. In the acute stage of myocardial infarction (1-3 days), there is a significant increase in the concentrations of markers of interstitial myocardial fibrosis, such as tissue inhibitor of matrix metalloproteinase-1 and aldosterone, which reflects the initiation of fibroblast activation processes and, accordingly, stimulation of collagen synthesis. Subsequently, there is a decrease in the concentration of tissue inhibitor of matrix metalloproteinase-1 and aldosterone.

Myocardial involvement in eosinophilic granulomatosis with polyangiitis evaluated with cardiopulmonary magnetic resonance

Patients with eosinophilic granulomatosis with polyangiitis (EGPA) most commonly die from cardiac causes, however, cardiac involvement remains poorly characterised and the relationship between cardiac and pulmonary disease is not known. This study aimed to characterise myocardial and pulmonary manifestations of EGPA, and their relationship. Prospective comprehensive cardiopulmonary investigation, including a novel combined cardiopulmonary magnetic resonance imaging (MRI) technology, was performed in 13 patients with stable EGPA. Comparison was made with 11 prospectively recruited matched healthy volunteers. Stable EGPA was associated with focal replacement and diffuse interstitial myocardial fibrosis (myocardial extracellular volume 26.9% vs. 24.7%; p = 0.034), which drove a borderline increase in left ventricular mass (56 ± 9 g/m2 vs. 49 ± 8 g/m2; p = 0.065). Corrected QT interval was significantly prolonged and was associated with the severity of myocardial fibrosis (r = 0.582, p = 0.037). Stable EGPA was not associated with increased myocardial capillary permeability or myocardial oedema. Pulmonary tissue perfusion and capillary permeability were normal and there was no evidence of pulmonary tissue oedema or fibrosis. Forced expiratory volume in one second showed a strong inverse relationship with myocardial fibrosis (r = −0.783, p = 0.038). In this exploratory study, stable EGPA was associated with focal replacement and diffuse interstitial myocardial fibrosis, but no evidence of myocardial or pulmonary inflammation or pulmonary fibrosis. Myocardial fibrosis was strongly associated with airway obstruction and abnormal cardiac repolarisation. Further investigation is required to determine the mechanisms underlying the association between heart and lung disease in EGPA and whether an immediate immunosuppressive strategy could prevent myocardial fibrosis formation.

Abstract 17157: The SGLT2 Inhibitor Empagliflozin Ameliorates Interstitial Myocardial Fibrosis and Aortic Stiffness in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on interstitial myocardial fibrosis (IMF) and aortic stiffness has not yet been studied Hypothesis: Empagliflozin ameliorates IMF and aortic stiffness in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial (NCT 03485222) investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). IMF was assessed by CMR using extracellular volume (ECV) by T1 mapping. Aortic stiffness was quantified by pulse wave velocity (PWV) by CMR. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in ECV (ΔECV) and PWV (ΔPWV) at 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either ECV or PWV (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p<0.001; and ΔLVEF 6±4 vs 0±4%, p<0.001 for EMPA vs placebo). EMPA-treated patients exhibited a reduction in ECV (ΔECV -1.25±1.5 vs 0.3±1.4% for EMPA vs placebo, p<0.001), which demonstrates IMF regression with SGLT2i. EMPA-treated patients exhibited a reduction in PWV (ΔECV -0.6±1 vs 0.6±1.4 m/s for EMPA vs control, p<0.001), which indicates amelioration of aortic stiffness with SGLT2i Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates IMF and aortic stiffness. This may explain the benefits of SGLT2i in HFrEF even in the absence of diabetes