CONDITION OF INTRACARDIAC HEMODYNAMICS AND MICROCIRCULATION IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE AND CONCOMITANT DIFFUSE LIVER DISEASES

Introduction. It is known that patients with ischemic heart diseases have endothelial dysfunction, but there is lack of research about microcirculation in these patients with diffuse liver diseases, especially diagnosed with digital capillaroscopy. Aim. To investigate hemodynamic disorders and microcirculation in patients with chronic ischemic heart disease depending on the presence of diffuse liver diseases and its severity with the digital capillaroscopy. Materials and methods. Our prospective study included 187 patients according to the criteria of inclusion. The data of echocardiography and digital capillaroscopy were analysed. Results. In our research in patients with ejection fraction less than 40% there was revealed thickening of the wall of the left ventricle, low blood supply in arterial and venous parts of capillaries. Patients with ejection fraction less than 40% and progressive diffuse liver diseases had advanced thickening of the wall of the left ventricle. Patients with liver cirrhosis had more adverse changes in hemodynamics. Patients with ischemic heart disease and diffuse liver disease had the worst capillary blood supply. Patients with ejection fraction less than 40% and diffuse liver diseases had structural changes of capillaries such as bi-, trifurcation and bushy forms. Conclusions. So, diffuse liver diseases, especially severe, cause endothelial dysfunction in patients with ischemic heart diseases. Digital capillaroscopy is a noninvasive method for microcirculation diagnosis and patients’ monitoring. KEYWORDS

in the study according to the criteria of inclusion: presence of IHD and DLD. There was one more group with 30 healthy volunteers. The investigation was conducted according to the standards of Good Clinical Practice, Ukrainian medical law and all patients signed informed agreement. 187 patients were included in the study -34 women and 154 men from 18 to 85 years old (average age was 46,1±17,4). There were three groups in our study.
Transthoracic echocardiography (echo) was conducted on the device HDI 11XE Philips according to the general methodology [1] with measurement in 2D-regime of wall thickness of the right ventricle (Trv), posterior wall of the LV (Tlv), intraventricular septum (Tivs), short-axis size of the left atrium (LA), terminal diastolic volume (TDV) of LV by Simpson, its EF and also short-axis size of the RV in basal chamber (Drv(k)), diameter of vena cava inferior (VCI). Diastolic filling of the LV was evaluated according to the ratio of transmitral flow velocity in the period of rapid filling and in systolic phase of the LA (E/A), time of decreasing of early diastolic filling velocity (DT) and duration of the period of left ventricular isometric relaxation (IVRT). Systolic pressure of the pulmonary artery (SPpa) was evaluated by the speed of tricuspid regurgitation flow.
Digital capillaroscopy (DC) was conducted on the device ООО «Micropotic» Kyiv with the programme AngioPro. The following data of DC were measured: diameter of the arterial part of the capillary (DAC), diameter of the venous part of the capillary (DVC), length of the arterial part (LAC) and venous part (LVC) of the capillary, blood flow velocity of the arterial part (FVAC) and venous part of the capillary (FVVC). Statistical analyses was made with Statistica for Windows 7.0 (Statsoft, USA). Distribution of the values wasexpressed as median, mean and Shapiro-Wilk criterion. Comparing groups was held with Vilkokson-Mann-Witney criterion. Reliability of nonparametric data discrepancies in groups (including follow-up period) was made with Chi-square criterion. Correlation analyses was made with Pearson's correlation croterion. The discrepancies were statistically significant at р<0,05.
Results and discussion. According to the recommendations of the Ukrainian association of cardiologists of diagnosis, treatment and prevention of CHI in adults (2017) we divided our patients into two groups: group 1 with normal EF of the LV systolic function (EFlv>40%) and group 2 with reduced EF (EFlv<40%). For additional evaluation of the stage of diastolic dysfunction of LV we created subgroups with E/A more and less than 1 in every group. We evaluated the fact that Е/А>1,0 at EFlv<40% was related to the pseudonormal/restricrive type of transmitral flow and in case of EFlv>40% Е/А>1,0 better diastolic filling of LV was performed comparing the patients with Е/А<1,0 (diastolic dysfunction of the LV by relaxation disorder type). Part of the patients with concomitant DLD among the patients with EFlv> 40% was 41% and among the patients with EFlv<40% -50%.
The data of intracardiac hemodynamics of the both groups confirmed the dilatation of the ventricles and LA, thickening of the ventricles' walls, increasing of the pressure in the pulmonary artery, size of the VCI ( Table 2). Patients with EFlv<40% had elevated data of TDV, Tivs, Tlv, SPpa, VCI comparing to the patients with EFlv>40%. Patients with EFlv>40% and Е/А>1,0 had less thickening of the walls of LV and this provd the dependence of LV rigidity from the thickness of its walls. Patients with EFlv<40% and Е/А>1,0 had higher data of TDV and LA and lower data of IVRT і DT comparing to the subgroup with EFlv<40% and Е/А<1,0 which proved the increased load of the ventricles and LA at pseudonormal and restrictive types of diastolic dysfunction. Table 2. Data of echo in patients with IHD depending on the condition of systolic and diastolic functions of LV Data of EchoKG M±SD We have analysed the data of DC in patients with IHD (Table 3) and have found decrease of DAC, DVC, FVAC and FVVC which proved the reduction of capillary flow as a result of mio-and neurotone elevation, peripheral resistance venous outflow dysfunction due to CHI. In patients with EFlv<40% decreased data of FVAC and FVVC demonstrated the reduction of blood supply of microcirculation due to [4] reduced cardiac output and blood volume in capillaries and elevation of tone of vessels of middle and small calibres as a result of activated sympathetic-adrenal system (SAS), renin-angiotensin-aldosterone system and hyperproduction of vasoconstrictors [5]. Table 3. Data of DC in patients with IHD depending on the condition of systolic and diastolic functions.
Data of DC M±SD The results of echo investigation in the groups are presented in Table 4. All the patients with IHD had enlargement of cavity and thickening of the wall of LV with its contraction dysfunction and diastolic filling, enlargement of cavity and thickening of the wall of RV, enlargement of the LA and VCI, elevation of pressure in the PA. Patients with IHD had higher degree of dysfunction of structural and functional changes of different heart chambers comparing to the patients with DLD. Patients with IHD and concomitant DLD had higher data of Trv, EFlv and lower data of TDVlv. We analyzed the data of echo of our patients with IHD and concomitant DLD according to the similar data of EFlv because it was difficult to evaluate classical clinical criteria of heart insufficiency such as stuffiness, tachycardia, hepatomegaly, oedema, ascites, hydrothorax etc. (Table 5). Patients with IHD and EFlv>40% and with DLD had thickening of the walls of the ventricles at analyzing the data of echo. Patients with EFlv<40% and DLD had significantly advanced thickness of the wall, short size of the RV and diameter of VCI. The main cause of the remodeling processes of RV and LV could be changes of metabolism of vasoactive factors and liver hemodynamic dysfunction. We analysed the data of echo in patients with DLD depending on the liver damage for understanding the influence of concomitant DLD on the condition of hemodynamics in patients with IHD ( Table 6). The worst prognostic data were revealed in patients with LC. In our study the most significant changes of hemodynamics were revealed in patients with LC and included the enlargement of the walls and cavity of the ventricles, dysfunction of contraction and filling of the left ventricle, dilatation of the left atrium, pulmonary hypertension (Table 7). According to the results of DC (Table 8) in patients with IHD and without DLD there was reduction of LAC, LVC, FVAC and FVVC due to the elevation of SAS and local peripheral resistance [6]. Patients with DLD had decreased FVAC and FVVC as the result of the remodeling of capillary flow. Patients with IHD and DLD had higher stage of capillary flow disorder due to the production of inflammatory cytokines and disturbances of its utilization by the liver. We also revealed in our study that there was different pathomorphology of capillary flow changes. Patients with IHD and DLD had long forms because of elevation of peripheral resistanse, spasm of precapillary sphincters and activation of SAS. Patients with DLD had more tortuous and distorted short capillary loops which proved the dysfunction of outflow. Patients with IHD had lower DAC as the result of elevation of local peripheral resistanse and reduction of microcirculation [7]. According to the results of our analyses (Table 9) patients with EF>40%, IHD and DLD had accelerated data of DAC, lower data of FVAC as the result of decreasing of arteriole tone and dilatation of precapillary sphincters. It could be caused by the changes of liver function with elevation of vasodilatators such as nitric oxide, prostacyclin and glucagon and decreased sensitivity of arteriole to the catecholamines and angiotensin-II etc. [7]. Patients with EFlv<40% with DLD had lower data of FVAC due to the decreased tone (paresis) of precapillary sphincters and decreased FVVC as a result of stasis (disturbed venous outflow). It could be caused by hyperproduction of tumornecrotic-factorand interleukines-1,6,8, metabolism disturbances of vasoconstrictors by the damaged liver. That is why patients have structural changes of capillaries such as bi-, trifurcation and bushy forms. Patients with IHD and stages of EFlv decrease had clear signs of reduction blood supply due to the disturbances of central hemodynamics, atherosclerosis of vessels and elevation of its tone. In patients with IHD and DLD we didn't find the decreasing of DC data according to the lowering of EFlv.
Patients with IHD and DLD with EFlv>40% had tendency to the decrease of vessels' tone and microcirculation compared to the patients without DLD due to the oedema of Disse's space, reduced numbers of star-shaped cells, metabolism disorder of extracellular matrix-proteins, chemokines, cytokines, liver fibrosis. According to the results of DC data in patients with DLD of different etiology (Table 10) the worst stage of hemodynamic disorder was revealed in patients with LC. In groups with CTH and NASH the DAC was the biggest due to the disorder of liver utilization of glucagon, prostaglandins, adenosine, biliary acids and etc. In our study we revealed (Table 11) that with DLD of minimal liver damage had slighter changes of DAC, DVC, FVAC and FVVC compared to the patients with LC due to the decreased tone of precapillary sphincters and elevation of capillary blood supply. Patients with moderate syndrome of cytolysis/cholestasis had slighter disorder of venous outflow, decreasing of peripheral resistance of precapillaries according to the DAC and DVC data and capillary microcirculation according to the FVAC and FVVC compared to the patients with LC due to the hyperproduction of the proinflammatory cytokines. Elevation of liver damage was characterized by phases changes of DAC, FVVC and FVAC due to the hyperactivity of L-arginine-NO and depletion of reticulo-endothelial system of liver in heavy hepatitis and LC [8][9][10]. The highest stage of liver blood supply dysfunction was in patients with LC due to the hyperproduction and/or disorder of vasoconstrictor utilization and structural and functional changes in the liver [11][12][13][14]. Abbreviations: continuous variables were expressed as median (interquartile range). *u<0,05 comparing to the control with Vilkokson-Mann-Witney criterion. ^ u <0,05 comparing to the patients with LC. # u <0,05 comparing to the patients with DLD of moderate and minimal damage.
In our study correlation analyses demonstrated significant correlation of the data of DC and echo (Table 12) and could be the bases for further investigation of diagnostic value of DC in evaluation of intracardiac hemodynamic and capillary circulation. Conclusions. So, we revealed in our study that patients with IHD and reduction of contraction of LV and its diastolic filling had progressive microcirculatory supply disorder. There was also found that concomitant DLD in patients with IHD worsened significantly systolic and diastolic functions of LV, aggravated CHI, especially in patients with LC. In our investigation it was proved that presence of IHD and DLD caused disorder of cytomicroarchitectonics of the capillaries. We demonstrated value of DC in investigation of microcirculatory disorders to detect stages of blood supply disorders and to be noninvasive device for monitoring patients with IHD and concomitant DLD.