Effect of 24-hour blood pressure and heart rate on the prognosis of patients with reduced and midrange LVEF.

Aim    Optimal combination therapy for chronic heart failure (CHF) currently implies the mandatory use of at least four classes of drugs: renin-angiotensin-aldosterone (RAAS) system inhibitors or angiotensin receptor blocker neprilysin inhibitors (ARNI); beta-adrenoblockers (BAB); mineralocorticoid receptor antagonists; and sodium-glucose cotransporter 2 inhibitors. Furthermore, many of these drugs are able to decrease blood pressure even to hypotension and alleviate tachycardia. This study focused on the relationship of 24-h blood pressure (BP) and heart rate (HR) with the prognosis for CHF patients with sinus rhythm and left ventricular ejection fraction (LV EF) <50 % as well as on suggesting possible variants of safe therapy for CHF depending on the combination of studied factors.Material and methods    Effects of clinical data, echocardiographic parameters, 24-h BP, and heart rhythm (data from 24-h BP and ECG monitors) on the prognosis of 155 patients with clinically pronounced CHF, LV EF <50 %, and sinus rhythm who were followed up for 5 years after discharge from the hospital.Results    The one-factor analysis showed that the prognosis of CHF patients was statistically significantly influenced by the more severe functional class (FC) III CHF compared to FC II, reduced LV EF (<35 %), a lower 24-h systolic BP (SBP) (<103 mm Hg), the absence of hypotensive episodes in daytime, a low variability of nighttime BP (<7.5 mm Hg), a higher 24-h HR (>71 bpm vs. <60 bpm), the absence of therapy with RAAS inhibitors + BAB, and a lower body weight index. The multi-factor analysis showed that more severe CHF FC, lower LV EF, and the absence of RAAS inhibitors + BAB therapy retained the influence on the prognosis. After eliminating the influencing factor of drug therapy, also a low SBP variability significantly influenced the prognosis. An additional analysis determined the following four groups of CHF patients with reduced heart systolic function according to mean 24-h HR and SBP: the largest group (38.1 % of all patients) with controlled HR (≤69 bpm), preserved SBP (>103 mm Hg), and the lowest death rate of 15.3 %; the group with increased HR (>69 bpm) but preserved SBP (30.3 % of all patients) where the death rate was 44.7 %, which was significantly higher than in the first group; the group with normal HR (≤69 bpm) but reduced SBP (≤103 mm Hg) (16.1 % of patients) where the death rate was 40 %, which was comparable with the second group and significantly worse than in the first group; and the group with both increased HR (>69 bpm) and reduced SBP (≤103 mm Hg) (15.5 % of patients), which resulted in the maximal risk of death (70.8 % of patients with CHF and LV EF <50 %), which was significantly higher than in the three other groups.Conclusion    Low SBP (including 24-h SBP with reduced variability in day- and nighttime) in combination with high HR (including by data of Holter monitoring), low LV EF, more severe clinical course of CHF, and the absence of an adequate treatment with neurohormonal modulators (RAAS inhibitors and BAB) significantly increased the risk of death. Isolating four types of FC II-III CHF with sinus rhythm and EF <50% based on the combination of HR and BP identifies patients with an unfavorable prognosis, which will help developing differentiated therapeutic approaches taking into account clinical features.

[Telomere length as a biomarker of the risk of cardiovascular complications in patients with coronary heart disease].

AIM: To study the effect of oxidative stress and telomere length in the chromosomes of blood leukocytes in patients with coronary heart disease (CHD) on the development of cardiovascular complications. MATERIALS AND METHODS: In 119 patients with CHD, the level of oxidatively modified low-density lipoproteins (ox-LDL) in blood plasma and the length of telomeres in nuclear blood cells were determined during the examination. After 5 years, a telephone survey of patients (or their relatives) was conducted to obtain data on the presence of cardiovascular complications. Telomere length was determined using quantitative real-time PCR, and the level of ox-LDL was determined by immunochemical method. RESULTS: It was found that reducing the length of telomeres in patients with CHD increases the risk of subsequent development of cardiovascular complications. A strong negative correlation was found between the level of ox-LDL and telomere length in the group of examined CHD patients who had cardiovascular complications after 5 years. CONCLUSION: CHD patients with short telomere length and high levels of ox-LDL have an increased risk of cardiovascular complications during 5 years.

[Inflammatory infiltrates, vasa vasorum, and endothelial NO synthase in the wall of thoracic aortic aneurysm]. / Vospalitel'nye infil'traty, vasa vasorum i NO-sintaza éndoteliia v stenke anevrizmy grudnogo otdela aorty.

OBJECTIVE: To elucidate whether there is a relationship between inflammation of the wall of aortic aneurysm and the number of vasa vasorum in it. MATERIAL AND METHODS: The investigation material was aortic aneurysm wall segments obtained during surgery. Among the patients, there were 20 men and 5 women. The patients' age ranged from 33 to 69 years. The investigation used monoclonal antibodies to macrophages (CD68), T cells (CD3, CD4, and CD8) and antibodies to von Willebrand factor, endothelial NO synthase, and alpha smooth muscle actin. A morphometric study was conducted. RESULTS: Calculation of the number of vasa vasorum (including newly formed vessels) in the adventitia of aortic aneurysm revealed that there was a statistically significant difference between the number of vasa vasorum in patients with an active inflammatory response (Group 1) versus Group 2 patients with a moderate inflammatory process in the aneurysm wall (p≤0.05) and a statistically significant difference between Groups 1 and 3 (without inflammatory infiltrates) (p≤0.05). Endothelial vasa vasorum heterogeneity was found in case of an immune response to NO synthase. At the same time individual vasa vasorium did not contain NO synthase, this enzyme was identified in the endothelium in a number of nearby vessels. CONCLUSION: The increase in the number of vasa vasorum in the aneurysm wall in patients with abundant inflammatory infiltrates is due to the fact that some of the inflammatory cytokines of T-cells and macrophages also contribute to angiogenesis.

[Adhesion Molecules and Subpopulation of Mononuclear Cells in Pulmonary Arteries].

Atherosclerosis is associated with increased expression of adhesion molecules by vascular endothelium. AIM: to study endothelial expression of platelet endothelial cellular adhesion molecules (PECAM) (CD31), intercellular adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1F) as well as T-cells and monocytes adhered to endothelium. METHODS: Research materials were en face specimens.

[Results of using the dosing Valsalva-Weber test to determine autonomic disorders in patients with vasovagal syncope].

AIM: To estimate the value of the dosing Valsalva-Weber test (VWT) in the diagnosis of autonomic disorders in patients with vasovagal syncope (VVS). SUBJECTS AND METHODS: The dosing VWT using a specialized Task Force Monitor unit ("CNSystem", Austria) with synchronous noninvasive ECG and blood pressure (BP) monitoring was carried out in 30 patients (mean age 32 ± 14 years) with VVS and 12 healthy individuals (31 ± 7 years). The analysis of the test results encompassed the visual assessment of BP change curves and heart rate in different test phases and the calculation of pressure indices, Valsalva coefficient, arterial baroreflex sensitivity, and other parameters (a total of 26). RESULTS: The abnormally changed form of the mean BP curve, which was characterized by that BP by the end of Phase II test failed to achieve the baseline level, was recorded in 10 (33%) patients with VVS and in none of the healthy individuals (p = 0.04). An individual analysis of the gender- and age-adjusted Valsalva coefficient revealed its reduction in 9 (30%) patients while this indicator was within the normal range in all the healthy individuals (p = 0.04). CONCLUSION: During the dosing VWT, the signs of sympathetic insufficiency (impaired adrenergic regulation of BP) are found in 33% of the patients with VVS and those of parasympathetic insufficiency (impaired vagus regulation of cardiochronotropic function) are in 30%.

[Influence of intensive hypolipidemic therapy on blood concentration of lipoprotein-associated phospholipase A2 in patients with ischemic heart disease].

AIM: To assess the impact of combined treatment with simvastatin and ezetimibe or treatment with simvastatin only on lipoprotein-associated phospholipase A2 in patients with ischemic heart disease. METHODS: One hundred patients with angiographically documented coronary atherosclerosis took part in the investigation. Lp-PLA2 mass and cholesterol fractions were determined at baseline and after 6 months of treatment. Lp-PLA2 mass was determined by enzyme immunoassay method, using two highly specific monoclonal antibodies. RESULTS: Combined treatment with ezetimibe and simvastatin led to significantly greater declines in Lp-PLA2 and cholesterol fractions compared with treatment only with simvastatin: Lp-PLA2 decreased by 46 vs 38%, total cholesterol by 35 vs 28%, LDL cholesterol by 50 vs 40%, respectively (p<0.05). Combination therapy with ezetimibe and simvastatin 20 and 40mg/day proved to be as effective as monotherapy with simvastatin 80 mg/day on the effect on Lp-PLA2 mass and cholesterol fractions (p<0.05). Lp-PLA2 correlated positively with total cholesterol (r=0.28) and LDL-C (r=0.33). CONCLUSIONS: Combined treatment led to greater reduction of total cholesterol and LDL-C, as well as significantly reduced level of Lp-PLA2 mass. The latter can be considered as target for suppression of inflammation and achievement of stabilization of atherosclerotic plaque.

[Spectral indices of heart rate variability in patients with vasovagal syncopes according to evidence of 5-min ECG].

AIM: To compare autonomic nervous system activity estimated by power spectral analysis of heart rate variability in patients with vasovagal syncopes and healthy volunteers. MATERIAL AND METHODS: Seventeen health volunteers and 25 patients with vasovagal syncope were included in the study. In 16 cases faints were induced by head-up tilt table test (HTT), in 9 cases--by bicycle exercise test (BET). Power spectral analysis of heart rate variability in 5-th min ECG records was performed in supine and upright position while breath was fixed. RESULTS: In supine position the data of low frequency (LF) and high frequency (HF) of spectral power in both groups of patients were significantly higher than in volunteers. During upright the HF of spectral power significantly decreased in patients and volunteers. In upright position LF of spectral power significantly decreased in patients with syncope induced by HTT, did not change in patients with syncope induced by BET, but significantly increased in volunteers. CONCLUSION: Patients with vasovagal syncope had abnormal autonomic nervous system activity: a high level of parasympathetic influence in supine position and poor reaction of sympathetic nervous system during upright.

[Optimization of use of beta-adrenoblockers in the treatment of chronic heart failure in the outpatient setting].

AIM: to evaluate of the effectiveness of switching from beta-adrenoblockers (BAB) non-included into the guidelines for the management of chronic heart failure (CHF) to nebivolol and bisoprolol for outpatients. SUBJECTS AND METHODS: The study included 67 patients with stable Functional Classes (FC) II and II CHF who received the standard therapy and BAB non-included into the guidelines for the management of CHF. The patients were randomized to the groups taking bisoprolol (n = 35) or nebivolol (n = 32) in doses of 1.25 to 10 mg/day. Before and 6 months after therapy, the investigators assessed the patient's clinical status and quality of life (QL), performed a six-minute walk test and echography, and determined the blood level of the N-terminal fragment of brain natriuretic peptide prohormone (NT-proBNP). RESULTS: The switching to bisoprolol and nebivolol was followed by a significant clinical improvement, a larger covered distance, and better QL. Left ventricular ejection fraction was increased along with a reduction in mean FC CHF. There were no significant changes in NT-proBNP in the total patient group, but it was significantly decreased in the subgroup of those with the baseline high level of the peptide. CONCLUSION: The switching of patients with stable CHF from therapy with BAB not included into the guidelines for the management of CHF to nebivolol or bisoprolol yields positive results and improves left ventricular systolic function (which is attended by the reduction in NT-proBNP levels) and may be recommended for treatment in the outpatient setting.

[Dynamics of ECG voltage in changing gravity].

Comparative analysis of the QRS voltage response to gravity variations was made using the data about 26 normal human subjects collected in parabolic flights (CNERS-AIRBUS A300 Zero-G, n=23; IL-76MD, n=3) and during the tilt test (head-up tilt at 70 degrees for a min and head-down tilt at-15 degrees for 5 min, n=14). Both the parabolic flights and provocative tilt tests affected R-amplitude in the Z lead. During the hypergravity episodes it was observed in 95% of cases with the mean gain of 16% and maximal--56%. On transition to the horizontal position, the Rz-amplitude showed a rise in each subject (16% on the average). In microgravity, the Rz-amplitude reduced in 95% of the observations. The voltage decline averaged 18% and reached 49% at the maximum. The head-down tilt was conducive to Rz reduction in 78% of observations averaging 2%. Analysis of the ECG records under changing gravity when blood redistribution developed within few seconds not enough for serious metabolic shifts still revealed QRS deviations associated exclusively with the physical factors, i.e., alteration in tissue conduction and distance to electrodes. Our findings can stand in good stead in evaluation of the dynamics of predictive ECG parameters during long-term experiments leading to changes as in tissue conduction, so metabolism.

[Comparative efficacy and tolerance of atenolol and midodrine in patients with vasovagal syncopes].

AIM: To compare efficacy and tolerance of atenolol and midodrine in patients with vasovagal syncopes (VVS). MATERIAL AND METHODS: The trial included 35 patients with recurrent VVS confirmed at long passive head-up tilt table test (HTTT) or maximal load bicycle exercise test (MET). These tests were also used for assessing efficacy of atenolol and midodrine in cases when syncopes occur in repeated tests. If recurrent induction of VVS was absent, efficacy of the drugs was assessed by long-term (up to 12 months) clinical observation. Long-term administration of atenolol and midodrine was continued in patients with effect by HTTT and/or MET. Eighteen patients were randomized to take atenolol in a daily dose up to 50 mg, seventeen--to take midodrine in a daily dose up to 15 mg. RESULTS: Efficacy of atenolol by HTTT and MET was 8%, midodrine--57% (p = 0.01). All the patients benefited from the drugs in their long-term regimen. Long-term administration of atenolol induced remission of VVS in 82% cases, midodrine--in 89% (insignificant). Overall efficacy of atenolol was 44%, of midodrine--70% (insignificant). In 5 of 6 patients resistant to atenolol and midodrine monotherapy, combined use of the drugs was effective. Treatment with atenolol, midodrine and their combination prevented VVS in 89% patients. Both short- and long-term courses of atenolol and midodrine were safe in terms of side effects. CONCLUSION: Atenolol and midodrine as well as their combination were highly effective and well tolerated in the treatment of VVS patients.

[Results of midodrin treatment of vasovagal syncope]. / Rezul'taty primeneniia midodrida dla lecheniia bolnykh vazovagal'nymi obmorokami.

AIM: To elicit efficacy of midodrin in patients with vasovagal syncope. MATERIAL AND METHODS: 50 patients with recurrent vasovagal syncope documented by head-up tilt tests or bicycle exercise stress tests participated in the study. These tests controlled the effects of midodrin if syncopes occurred again in repetition of the tests. In the other patients the effect of the drug was assessed clinically. All the patients received midodrin in daily dose up to 15 mg. RESULTS: Mirodrin effectively prevented syncope in 13 (72%) patients as shown by the tilt test, in 10 (59%) patients as shown by the exercise stress tests and in 14 (93%) patients as controlled clinically. Total efficacy of midodrin was 74% (37 of 50 patients). CONCLUSION: Midodrin demonstrated high efficacy in prevention of vasovagal syncope. Side effects were not serious therefore the drug is well tolerated.

[Long-term orthostatic and bicycle ergometry exercise tests in differential diagnosis of syncopal conditions of unclear origin]. / Vozmozgnosti dlitel'noi ortostaticheskoi i veloérgometricheskoi prob pri differentsial'noi diagnostike sinkopal'nykh sostoianii neiasnogo geneza.

AIM: To study efficiency of bicycle exercise test and long-term orthostatic test in differential diagnosis of syncopes. MATERIAL AND METHODS: The study included 113 patients suffering from recurrent syncopes of unclear origin. Twelve healthy volunteers were selected for assessment of the tests specificity. All the patients and controls were examined by means of long-term orthostatic test (LTOT) and bicycle exercise test (BET). RESULTS: Specificity of both tests was 100%. In LTOT syncopes were observed in 52 (46%) cases, including vasovagal syncopes (51 patients), epileptic seizure (1 patient). BET induced vasovagal syncopes in 54 (48%) patients. The results of both tests by inducing syncopes coincided in 30 (26%) cases. In 24 (21%) patients syncopes occurred only in BET while LTOT appeared uninformative. In 21 (18.6%) cases syncopes occurred only in LTOT while BET produced a negative result. 38 (34%) patients had syncopes neither in LTOT nor BET. Both tests induced syncopes in 75 (66%) patients. No complications were observed. CONCLUSION: LTOT and BET are safe and complementary methods in differential diagnosis of syncopes.

[Blood flow in affected major arteries of head in hypertensive patients]. / Sostoianie krovotoka v patologicheski izmenennykh magistral'nykh arteriiakh golovy u bol'nykh gipertonicheskoi bolezn'iu.

AIM: To assess blood flow in intracranial internal carotid and vertebral arteries in patients with essential hypertension (EH) and hemodynamically insignificant atherosclerotic lesions and deformities of major arteries of the head (MAH). MATERIALS AND METHODS: The blood flow was assessed in 55 untreated patients (mean age 53 +/- 1 years) with mild, moderate or severe hypertension. 20 healthy patients served control. Duplex scanning was performed using ACUSON unit. RESULTS: Total blood flow (Q) in hypertensive subjects appeared significantly subnormal. It was less in patients with hemodynamically insignificant atherosclerotic stenosis and flexures of the carotid and vertebral arteries than in patients with affection of the carotid arteries only. Q in MAH was lower in smokers than in non-smokers.

[The effect of diprivan on the indices of central hemodynamics and the heart conduction system]. / Vliianie diprivana na pokazateli tsentralnoi gemodinamiki i provodiashchuiu sistemu serdtsa.

Using impedance tetrapolar plethysmography and transesophageal electrical stimulation of the left ventricle, changes in central hemodynamic parameters have been assessed in 46 women during brief (up to 10 min) anesthesias with diprivanum. Bolus injection of diprivanum at a dose of 2.5 mg per 1 kg body weight was used. It has been demonstrated that diprivanum administration decreased BP, which was associated with a drop in total peripheral resistance and stroke volume that led to the absence of compensatory tachycardia to an increase in the cardiac output. The absence of compensatory tachycardia upon diprivanum administration is accounted for by a combined effect of vagotonic diprivanum action and its ability to inhibit moderately the automatic function of the sinoatrial node.

[Echocardiographic assessment of cardiac pump function using afterloading characteristics]. / Ekokardiograficheskaia otsenka nasosnoi funktsii serdtsa s pomoshch'iu postnagruzochnykh kharakteristik.

Seventy five patients and twenty healthy individuals were investigated by using cardiac ultrasound technique, followed by mathematical simulation of changes in left ventricular pressure during contraction. The findings show that the afterload characteristics based on a wealth of evidence for cardiac and left ventricular performance, unlike the conventional central hemodynamic parameters and cardiac phasic indices, enable the occult circulatory disorders to be revealed and the cardiac compliance with the arterial system to be assessed.