Shvartz, Vladimir A

Kruchinova S., Gendugova M., Namitokov A., Sokolskaya M., Gilevich I., Tatarintseva Z., Karibova M., Danilov V., Simakin N., Shvartz E., Kosmacheva E., Shvartz V.

Background: Despite the vast evidence of the beneficial effect of vagus nerve stimulation on the course of myocardial infarction confirmed in studies using animal models, the introduction of this method into actual clinical practice remains uncommon. Objective: The objective of our study was to evaluate the effect of transcutaneous vagus nerve stimulation (tVNS) on in-hospital and long-term outcomes for patients with ST-elevation myocardial infarction. Materials and Methods: A blind, randomized, placebo-controlled clinical trial was conducted. The participants were randomly split into two groups. The Active tVNS group was subjected to stimulation of the tragus containing the auricular branch of the vagus nerve. The Sham tVNS group underwent stimulation of the lobule. Stimulation was performed immediately on admission before the start of the percutaneous coronary intervention (PCI). Then, tVNS continued throughout the entire PCI procedure and 30 min after its completion. The primary endpoints were hospital mortality and 12-month mortality. The secondary endpoints were in-hospital and remote non-lethal cardiovascular events. The combined endpoint consisted of major adverse cardiovascular events (MACEs)—recurrent myocardial infarction, stroke/TIA, and overall mortality. Results: A total of 110 patients were randomized into the Active tVNS group (n = 55) and the Sham tVNS group (n = 55). The incidences of hospital mortality, cardiogenic shock, and AV block 3 were statistically less common in the Active tVNS group than in the Sham tVNS group (p = 0.024*, p = 0.044*, and p = 0.013*, respectively). In the long-term period, no statistical differences were found in the studied outcomes obtained following the construction of Kaplan–Meyer survival curves. When comparing groups by total mortality, taking into account hospital mortality, we observed a tendency for the survival curves to diverge (Logrank test, p = 0.066). Statistical significance was revealed by the composite endpoint, taking into account hospital events (Logrank test, p = 0.0016*). Conclusions: tVNS significantly reduced hospital mortality (p = 0.024*), the level of markers of myocardial damage, and the frequency of severe cardiac arrhythmias in patients with acute myocardial infarction. In the long term, the prognostic value of tVNS was revealed by the composite endpoint major adverse cardiovascular events. Further studies with an expanded sample are needed for a more detailed verification of the data obtained to confirm the effectiveness of tVNS and allow an in-depth analysis of the safety and feasibility of its use in routine clinical practice. This clinical trial is registered with ClinicalTrials database under a unique identifier: NCT05992259.

Karibova M.V., Kruchinova S.V., Shvartz V.A., Gendugova M.N., Kosmacheva E.D.

Background: Heart failure is the outcome of most cardiovascular diseases. Its prevalence continues to increase annually, which emphasizes the importance of developing therapeutic strategies to prevent adverse outcomes. This article reviews current data on the effect of vagus nerve stimulation on the course of chronic heart failure.Objective: To summarize available literature data on the effect of vagus nerve stimulation on the course of chronic heart failure.Materials and methods: We searched PubMed and eLIBRARY for the relevant information over the last 20 years using the following keywords: vagus nerve, heart failure, stimulation, ejection fraction. The search was performed by titles, abstracts, and keywords.Results: This review revealed that vagus nerve stimulation has favorable effects in patients with heart failure and warrants further careful investigation.

Kiselev A.R., Posnenkova O.M., Karavaev A.S., Shvartz V.A., Novikov M.Y., Gridnev V.I.

Objective—Heart rate variability (HRV) and photoplethysmographic waveform variability (PPGV) are available approaches for assessing the state of cardiovascular autonomic regulation. The goal of our study was to compare the frequency-domain features and low-frequency (LF) synchronization of the PPGV and HRV with increasing severity of cardiovascular diseases. Methods—Our study included 998 electrocardiogram (ECG) and finger photoplethysmogram (PPG) recordings from subjects, classified into five categories: 53 recordings from healthy subjects, aged 28.1 ± 6.2 years, 536 recordings from patients with hypertension (HTN), 49.0 ± 8.8 years old, 185 recordings from individuals with stable coronary artery disease (CAD) (63.9 ± 9.3 years old), 104 recordings from patients with myocardial infarction (MI) that occurred three months prior to the recordings (PMI) (65.1 ± 11.0 years old), and 120 recordings from study subjects with acute myocardial infarction (AMI) (64.7 ± 11.5 years old). Spectral analyses of the HRV and PPGV were carried out, along with an assessment of the synchronization strength between LF oscillations of the HRV and of PPGV (synchronization index). Results—Changes in all frequency-domain indices and the synchronization index were observed along the following gradient: healthy subjects → patients with HTN → patients with CAD → patients with PMI → patients with AMI. Similar frequency-domain indices of the PPGV and HRV show little relationship with each other. Conclusions—The frequency-domain indices of the PPGV are highly sensitive to the development of any cardiovascular disease and, therefore, are superior to the HRV indices in this regard. The S index is an independent parameter from the frequency-domain indices.

Shvarts V.A., Talibova S.M., Sokolskaya M.A., Ispiryan A.Y., Shvarts E.N., Petrosyan A.D., Merzlyakov V.Y., Skopin A.I., Donakanyan S.A.

Aim. To compare the levels of novel biomarkers of systemic inflammation in pati­ents with and without atherosclerosis, as well as between groups of patients with atherosclerosis of different severity.Material and methods. Patients with suspected coronary artery disease after selective coronary angiography were included. The analysis included 901 patients with mean age of 61±10 years (men, 60% (n=549)). The patients were divided into two following groups: with and without atherosclerosis. The Propensity Score Matching method was used to adjust for baseline clinical differences.Results. In the group with atherosclerosis, the values of the systemic inflam­mation response index (SIRI), systemic immune-inflammation index (SII) and ag­gregate index of systemic inflammation (AISI) were significantly higher than in patients without atherosclerosis: 0,906 (0,632; 1,36) vs 0,745 (0,519; 1,02), p<0,001; 457 (350; 641) vs 425 (313; 547), p=0,005 and 233 (148; 346) vs 179 (121; 263), p<0,001, respectively. ROC analysis showed the following threshold values of the studied parameters: for SIRI >1,05, area under the curve (AUC) confidence interval (CI) — 0,615 (0,571-0,658), p<0,001, sensitivity — 42,6%, specificity — 77,3%; for SII >368, AUC CI — 0,572 (0,528-0,616), p=0,004, sensitivity — 72,1%, specificity — 43,4%; for AISI >248, AUC CI — 0,604 (0,560-0,647), p<0,001, sensitivity 47,4%, specificity 71,1%. SIRI had the highest AUC. When comparing 6 groups according to the Coronary Artery Surgery Study (CASS) classification, significant differences were found in SIRI and AISI, p<0,001 and p=0,0016, respectively. However, these differences did not have a logical pattern.Conclusion. Novel markers of systemic inflammation (SIRI, SII and AISI) were significantly higher in patients with confirmed atherosclerosis than in patients without it. There are following threshold levels associated with atherosclerosis: for SIRI >1,05, for SII >368, for AISI >248.

Boyadzhyan G.A., Donakanyan S.A., Shvartz V.A., Petrosyan A.D., Koasari A.K., Sanakoev M.K., Ispiryan A.Y., Aygumov R.N., Bockeria L.A.

Objective: to evaluate the hospital results of coronary artery bypass grafting using autoarterial and au-tovenous conduits. Material and methods. A randomized clinical trial was conducted. The internal thoracic artery on the left was used in both groups (for shunting the anterior interventricular branch), the remaining conduits, depending on the distribution into groups, were either only the radial artery or the radial artery and the large subcutaneous vein (the study group) or only the large subcutaneous vein (the control group). The outcomes studied were: hospital mortality, myocardial infarction (type 5), cerebrovascular events, respiratory failure, bleeding, cardiac arrhythmias, acute kidney injury, etc. Results. 27 patients were randomized: 12 of whom were included in the study group, and 15 were included in the control group. According to operational and early postoperative data, there were no statistically significant differences between the groups, except for the duration of stay on a ventilator in the ICU: in the study group, the duration of a ventilator was longer than in the control group: 14 (12; 18) hours versus 9.3 (5.8; 13) hours, p=0.034. The most frequent complications were cardiac arrhythmias, as well as AKI. There were no statistically significant differences between the groups according to the outcomes studied. The bed-day after surgery also did not differ statistically significantly between the groups. Conclusion. According to the data obtained, it can be concluded that the first days after surgery, the use of the radial artery does not provide significant advantages compared to the use of a large saphenous vein.

Olga N. D., Rogozhkina E.A., Shvartz V.A., Shvartz E.N., Kiselev A.R., Drapkina O.M.

Objective –– to compare heart rate variability (HRV) in patients aged 30-60 years without chronic noncommunicable diseases (CNCDs) with and without obesity. Methods –– The groups of obese (n=43) and nonobese (n=28) patients without CNCDs ranged 30 through 60 years of age. We assessed the conventional HRV indices according to the clinical guidelines, as well as the synchronization index (S) for low-frequency (LF) oscillations evaluated from HRV and photoplethysmogram (PPG). Results –– No statistically significant differences in HRV indices and S index were detected between the study groups. Conclusion –– HRV indices and synchronization of LF oscillations detected from HRV and PPG were not significantly associated with obesity in patients aged 30-60 years without CNCDs.

Krylova A., Svobodov A., Tumanyan M., Levchenko E., Kotov S., Butrim Y., Shvartz V.

Introduction: Surgical treatment of aortic coarctation in low-birth-weight (LBW) neonates is associated with risks of higher hospital mortality rates and recoarctation development in the long-term. The goal of our study was to compare the results of surgical treatment of aortic coarctation in LBW neonates and normal-weight patients, to identify predictors of recoarctation in the long-term among LBW patients. Materials and methods: A retrospective study was performed to analyse the patients who had undergone resection of isolated aortic coarctation between 2005 and 2022. Overall analysis included 521 patients under the age of 30 days, 89 LBW patients and 432 patients with normal body weight. Propensity score matching (PSM) was performed at a ratio of 1:1 for the statistical adjustment of original patients’ data in both groups. Results: All patients underwent standard resection of aortic coarctation with extended end-to-end anastomosis. Hospital mortality among LBW patients was 8% and in patients with normal weight the mortality amounted to 1% (p = 0.030). LBW patients were transferred to other hospitals more often than normal-weight patients who were more often discharged (p < 0.001). In the long-term, period mortality was not statistically significantly different (p = 0.801). The freedom from reoperation in the group of normal-weight children was 87%, whereas in the LBW patients the rate was 63% (log rank test, p = 0.104). In the multivariate regression model, the most significant risk factors for reoperation were as follows: preoperative inotropes administration (OR (95% CI) 4.369 (1.316–14.51)) and pressure gradient across aortic arch before discharge (OR (95% CI) 1.081 (1.014–1.153)). Conclusions: Hospital mortality was higher among LBW patients (p = 0.030). There was a statistical trend of differences in reoperation rates: in the long-term among LBW patients, a higher reintervention probability remains. Moreover, the LBW group initially had more severe clinical condition in terms of cardiac failure and impaired renal function. Factors associated with the risk of recoarctation were preoperative inotropes infusion and pressure gradient across aortic before discharge.

Shvartz V., Sokolskaya M., Ispiryan A., Basieva M., Kazanova P., Shvartz E., Talibova S., Petrosyan A., Kanametov T., Donakanyan S., Bockeria L., Golukhova E.

Introduction. The pathogenesis of aortic stenosis includes the processes of chronic inflammation, calcification, lipid metabolism disorders, and congenital structural changes. The goal of our study was to determine the predictive value of novel biomarkers of systemic inflammation and some hematological indices based on the numbers of leukocytes and their subtypes in the development of early hospital medical conditions after mechanical aortic valve replacement in patients with aortic stenosis. Materials and methods. This was a cohort study involving 363 patients who underwent surgical intervention for aortic valve pathology between 2014 and 2020. The following markers of systemic inflammation and hematological indices were studied: SIRI (Systemic Inflammation Response Index), SII (Systemic Inflammation Index), AISI (Aggregate Index of Systemic Inflammation), NLR (Neutrophil/Lymphocyte Ratio), PLR (Platelet/Lymphocyte Ratio), and MLR (Monocyte/Lymphocyte Ratio). Associations of the levels of these biomarkers and indices with the development of in-hospital death, acute kidney injury, postoperative atrial fibrillation, stroke/acute cerebrovascular accident, and bleeding were calculated. Results. According to an ROC analysis, an SIRI > 1.5 (p < 0.001), an SII > 718 (p = 0.002), an AISI > 593 (p < 0.001), an NLR > 2.48 (p < 0.001), a PLR > 132 (p = 0.004), and an MLR > 0.332 (p < 0.001) were statistically significantly associated with in-hospital death. Additionally, an SIRI > 1.5 (p < 0.001), an NLR > 2.8 (p < 0.001), and an MLR > 0.392 (p < 0.001) were associated with bleeding in the postoperative period. In a univariate logistic regression, SIRI, SII, AISI, and NLR were statistically significant independent factors associated with in-hospital death. In a multivariate logistic regression model, SIRI was the most powerful marker of systemic inflammation. Conclusion. SIRI, SII, AISI, and NLR as novel biomarkers of systemic inflammation were associated with in-hospital mortality. Of all markers and indices of systemic inflammation in our study, SIRI was the strongest predictor of a poor outcome in the multivariate regression model.

Shvartz V., Sizhazhev E., Sokolskaya M., Koroleva S., Enginoev S., Kruchinova S., Shvartz E., Golukhova E.

Many previous studies have demonstrated that transcutaneous vagus nerve stimulation (VNS) has the potential to exhibit therapeutic effects similar to its invasive counterpart. An objective assessment of VNS requires a reliable biomarker of successful vagal activation. Although many potential biomarkers have been proposed, most studies have focused on heart rate variability (HRV). Despite the physiological rationale for HRV as a biomarker for assessing vagal stimulation, data on its effects on HRV are equivocal. To further advance this field, future studies investigating VNS should contain adequate methodological specifics that make it possible to compare the results between studies, to replicate studies, and to enhance the safety of study participants. This article describes the design and methodology of a randomized study evaluating the effect of short-term noninvasive stimulation of the auricular branch of the vagus nerve on parameters of HRV. Primary records of rhythmograms of all the subjects, as well as a dataset with clinical, instrumental, and laboratory data of all the current study subjects are in the public domain for possible secondary analysis to all interested researchers. The physiological interpretation of the obtained data is not considered in the article.

Kruchinova S., Shvartz V., Namitokov A., Gendugova M., Karibova M., Kosmacheva E.

(1) Background. One of the causes of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is thrombus formation in situ followed by lysis, resulting in a morphologically normal angiogram but with an underlying prothrombotic state that is potentially predisposed to recurrence. Recent studies have shown that a subset of MINOCA patients may have thrombophilic conditions at screening. Objective: To compare the prothrombotic trend in MINOCA patients with that of subjects with MI and obstructive coronary arteries (MIOCA) by testing for known congenital thrombophilias and markers of coagulation activation. (2) Materials and methods. Screening included congenital thrombophilias (factor V Leiden; assessment of protein C, protein S, and antithrombin III) and eight genes. Of these, four genes represented the folate pathway enzymes: MTHFR 677 C>T (rs1801133), MTHFR 1298 A>C (rs1801131), MTR 2756 A>G (rs1805087), and MTRR 66 A>G (rs1801394). The other four genes represented the blood coagulation system: F13 (163 G>T) rs5985, F1 (−455 G>A) rs1800790, GP IIb–IIIa (1565 T>C) rs5918, and PAI-I (−675 5G>4G) rs1799889. Additionally, we examined the levels of homocysteine and lipoprotein (LP) (a). (3) Results. Our study included 269 patients: 114 MINOCA patients and 155 MIOCA patients with lesions of one coronary artery. The frequencies of polymorphisms in the genes of the blood coagulation system and the folate pathway did not differ between the groups. The following genes were associated with in-hospital mortality in the MINOCA group: MTHFR 1298 A>C rs1801131 (OR 8.5; 95% CI 1.67–43.1) and F1 (−455 G>A) rs1800790 (OR 5.8; 95% CI 1.1–27.8). In the MIOCA group, the following genes were associated with in-hospital mortality: MTHFR 1298 A>C rs1801131 (OR 9.1; 95% CI 2.8–28.9), F1 (−455 G>A) rs1800790 (OR 11.4; 95% CI 3.6–35.9), GP IIb–IIIa (1565 T>C) rs5918 (OR 10.5; 95% CI 3.5–30.8), and PAI-I (−675 5G>4G) rs1799889 (OR 12.9; 95% CI 4.2–39.7). We evaluated long-term outcomes (case fatality rate, recurrent MI, and stroke) over a period of 12 months in both groups. The variables associated with these outcomes were laboratory parameters, such as protein C deficiency, hyperhomocysteinemia, and a content of LP (a) > 30 mg/dL. However, we did not reveal the prognostic value of polymorphisms of the studied genes representing the blood coagulation system and the folate pathway. (4) Conclusion. We established no statistically significant differences between the MINOCA and MIOCA groups in the prevalence of congenital thrombophilias and the prevalence of folate pathway enzyme genes and blood coagulation system genes. The MTHFR 1298 A>C (rs1801131) and F1 (−455 G>A) rs1800790 genes were associated with in-hospital mortality in both groups. More significant prognostic factors in both groups during the one-year period were protein C deficiency, hyperhomocysteinemia, and LP (a) > 30 mg/dL.

Shvartz V., Le T., Enginoev S., Sokolskaya M., Ispiryan A., Shvartz E., Nudel D., Araslanova N., Petrosyan A., Donakanyan S., Chernov I., Bockeria L., Golukhova E.

Background. In patients who underwent cardiac surgery, first-time postoperative atrial fibrillation (POAF) is associated with increased incidence of hospital-acquired complications and mortality. Systemic inflammation is one of confirmed triggers of its development. The anti-inflammatory properties of colchicine can be effective for the POAF prevention. However, the results of several studies were questionable and required further investigation. Hence, we aimed to evaluate the effectiveness of low-dose short-term colchicine administration for POAF prevention in patients after the open-heart surgery. This double-blind randomized placebo-controlled trial included 267 patients, but 27 of them dropped out in the course of the study. Study subjects received the test drug on the day before the surgery and on postoperative days 2, 3, 4 and 5. The rhythm control was conducted immediately after the operation and until the discharge from the hospital. The final analysis included 240 study subjects: 113 in the colchicine group and 127 in the placebo group. POAF was observed in 21 (18.6%) patients of the colchicine group vs. 39 (30.7%) control patients (OR 0.515; 95% Cl 0.281–0.943; p = 0.029). We observed no statistically significant differences between the patient groups in the secondary endpoints of the study (hospital mortality, respiratory failure, stroke, bleeding, etc.). For other parameters characterizing the severity of inflammation (pericardial effusion, pleural effusion, WBC count, neutrophil count), there were statistically significant differences between the groups in the early postoperative period (days 3 and 5). Also, statistically significant differences between the groups in the frequency of adverse events were revealed: the incidence of diarrhea in the colchicine group was 25.7% vs. 11.8% in the placebo group (OR 2.578; 95% Cl 1.300–5.111; p = 0.005); for abdominal pain, incidence values were 7% vs. 1.6%, correspondingly (OR 4.762; 95% Cl 1.010–22.91; p = 0.028). Thus, there were statistically significant differences between groups in the primary endpoint, thereby confirming the effectiveness of short-term colchicine use for the POAF prevention after coronary artery bypass grafting and/or aortic valve replacement. Also, we detected statistically significant differences between groups in the frequency of side effects to colchicine: diarrhea and abdominal pain were more common in the colchicine group. This clinical trial is registered with ClinicalTrials database under a unique identifier: NCT04224545.

M. A. S., V.A. S., A. S. K., V.V S.

Introduction — A well-known method for assessing the autonomic status of patients in clinical practice is the use of spectral estimates of finger's photoplethysmographic waveform variability (PPGV). However, these estimates have not been studied in patients with aortic stenosis. Therefore, this study aimed to identify in the PPGV spectrum the markers of autonomic dysfunction specific for patients with aortic stenosis. Methods — The study included 34 patients with aortic stenosis at the age of 54 (43, 67) years and 30 healthy subjects at the age of 34 (31, 36) years (data presented as median with lower and upper quartiles). The following spectral estimates of PPGV were evaluated: LF% (low-frequency band, 0.04–0.15 Hz, in the percentage of total spectral power, 0–0.4 Hz), HF% (high-frequency band, 0.15–0.4 Hz, in the percentage of total spectral power, 0–0.4 Hz), and LF/HF ratio. Results — The study revealed the statistically significant (p<0.05) differences in HF% and LF% values in patients with aortic valve disease compared with healthy people. LF% was increased by 2-4 times in group of patients with aortic stenosis, while HF% was increased by 1.2-7 times. The difference between the groups at LF/HF ratio was statistically insignificant. Conclusion — Patients with aortic stenosis are characterized by higher LF% and HF% values, relative to healthy people of comparable age.

Shvartz V., Khugaeva E., Kryukov Y., Sokolskaya M., Ispiryan A., Shvartz E., Petrosyan A., Dorokhina E., Bockeria L., Bockeria O.

Background: Acute kidney injury (AKI) is among the expected complications of cardiac surgery. Statins with pleiotropic anti-inflammatory and antioxidant effects may be effective in the prevention of AKI. However, the results of studies on the efficacy and safety of statins are varied and require further study. Methods: We conducted a retrospective cohort study to evaluate long-term preoperative intake of atorvastatin and rosuvastatin on the incidence of AKI, based on the “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria in the early postoperative period after coronary artery bypass graft surgery (CABG). We performed propensity score matching to compare the findings in our study groups. The incidence of AKI was assessed on day 2 and day 4 after the surgery. Results: The analysis included 958 patients after CABG. After 1:1 individual matching, based on propensity score, the incidence of AKI was comparable both on day 2 after the surgery (7.4%) between the atorvastatin group and rosuvastatin group (6.5%) (OR: 1.182; 95%Cl 0.411–3.397; p = 0.794), and on postoperative day 4 between the atorvastatin group (3.7%) and the rosuvastatin group (4.6%) (OR: 0.723, 95%Cl 0.187–2.792; p = 0.739). Additionally, there were no statistically significant differences in terms of incidence of AKI after 1:1 individual matching, based on propensity score, between the rosuvastatin group and the control group both on postoperative day 2 (OR: 0.692; 95%Cl 0.252–1.899; p = 0.611) and day 4 (OR: 1.245; 95%Cl 0.525–2.953; p = 0.619); as well as between the atorvastatin group and the control group both on postoperative day 2 (OR: 0.549; 95%Cl 0.208–1.453; p = 0.240) and day 4 (OR: 0.580; 95%Cl 0.135–2.501; p = 0.497). Conclusion: Long-term statin use before CABG did not increase the incidence of postoperative AKI. Further, we revealed no difference in the incidence of post-CABG AKI between the atorvastatin and rosuvastatin groups.

Shvartz V., Sokolskaya M.

Shvartz V., Sokolskaya M., Petrosyan A., Ispiryan A., Donakanyan S., Bockeria L., Bockeria O.

Background: Understanding of the risk factors for the development of adverse outcomes after aortic valve replacement is necessary to develop timely preventive measures and to improve the results of surgical treatment. Methods: We analyzed patients with aortic stenosis (n = 742) who underwent surgical treatment in the period 2014–2020. The average age was 63 (57;69) years—men 58%, women 42%. Results: The hospital mortality rate was 3% (22 patients). The following statistically significant threshold values (cut-off points) were obtained in the ROC analysis: aortic cross-clamp time > 93 min AUC (CI) 0.676 (0.640–0.710), p = 0.010; cardiopulmonary bypass time > 144 min AUC (CI) 0.809 (0.778–0.837), p < 0.0001, hemoglobin before op <120 g/L. AUC (CI) 0.762 (0.728–0.793), p < 0.0001, hematocrit before op <39% AUC (CI) 0.755 (0.721–0.786), p < 0.001, end-diastolic dimension index >2.39 AUC (CI) 0.647 (0.607–0.686), p = 0.014, end-systolic dimension index > 1.68 AUC (CI) 0.657 (0.617–0.695), p = 0.009. Statistically significant independent predictors of hospital mortality were identified: BMI > 30 kg/m2 (OR 2.84; CI 1.15–7.01), ischemic heart disease (OR 3.65; CI 1.01–13.2), diabetes (OR 3.88; CI 1.38–10.9), frequent ventricular ectopy before operation (OR 9.78; CI 1.91–50.2), mitral valve repair (OR 4.47; CI 1.76–11.3), tricuspid valve repair (OR 3.06; CI 1.09–8.58), 3 and more procedures (OR 4.44; CI 1.67–11.8). Conclusions: The hospital mortality rate was 3%. The main indicators associated with the risk of death were: diabetes, overweight (body mass index more than 30 kg/m2), frequent ventricular ectopy before surgery, hemoglobin level below 120 g/L, hematocrit level below 39%, longer cardiopulmonary bypass time and aortic cross-clamp time, additional mitral and tricuspid valve interventions.

Komarov R.N., Tsaregorodtsev A.V., Nuzhdin M.D.

The authors analyzed evolution of surgical and bioengineering approach to implantation and preparation of frameless human mitral valve for atrioventricular heart valve replacement. World and domestic experience in solving these problems is reflected. The authors analyze advanced methods in preparation of homografts that have the potential for the highest biocompatibility and rapid repopulation by own tissues.

Shvartz V., Danilov V., Koroleva S., Shvartz E., Donakanyan S., Permyakov V., Erastova N., Golukhova E., Radikovna B.A., Viktorovich K.V., Andreevna F.A., Vitalievich M.V., Kazbekovna P.Z., Nikolaevich S.V., Andreevich Y.A., et. al.

To obtain reference ranges for heart rate variability (HRV) parameters in healthy children, taking into account their gender and age. The study included the results of testing 22,468 children ranging 5.5–12.5 years of age. The data were grouped by age and gender. The analysis of HRV parameters was carried out according to the standards described in existing guidelines. It was based on a 5-min rhythmogram obtained from a standard 12-lead electrocardiogram (ECG). The following characteristics of the temporal and spectral analyses of HRV were studied: standard deviation of NN intervals (SDNN), power in the low-frequency band of the HRV spectrum (LF), low-frequency power as mean percentage of total power (TP) of HRV spectrum (LF%), power in the high-frequency band of the HRV spectrum (HF), high-frequency power as mean percentage of TP of HRV spectrum (HF%), power in the very-low-frequency band of HRV (VLF), and LF/HF ratio. The values of SDNN, LF, HF, HF% and TP increased with age, reaching a peak at 8 and 9 years of age. It is notable that the values of SDNN, LF and TP were significantly lower in girls in each age group. The values of LF% and LF/HF decreased with age, with a peak decrease at 8 and 9 years of age, followed by a moderate increase or stabilization. The values of LF% and LF/HF did not differ statistically significantly between boys and girls. The VLF parameter exhibited a clear trend of growth with age and had higher values in boys of each age group. The correlation between HRV and heart rate (HR) was statistically significant. The correlation graphs had similar curves in both gender groups and both age groups. The parameters of the total HRV, as well as the activity of the parasympathetic nervous system (PNS), exhibited similar growth trends with age, with a peak increase in their values at 8 and 9 years of age. HR, as well as the activity of the sympathetic nervous system (SNS), decreased with age. Gender differences also followed a consistent pattern: parameters characterizing the activity of the peripheral nervous system were significantly higher in boys than in girls across all age groups.

Higgs M., McDonagh J., Sim J.

This scoping review was undertaken to understand the degree of variation in clinical practices associated with postoperative atrial fibrillation (POAF), following coronary revascularization surgery by collating and synthesising key concepts from current published literature.

Kiselev A.R., Zhuravlev M.O., Runnova A.E.

This brief review discusses the potential and prospects of using the electrocardiogram (ECG) signal directly for frequency analysis to study the processes of cardiac regulation. The advantage of the ECG signal over the generally accepted frequency analysis of the RR series is its higher sampling rate: 1000 samples per second (sps) for ECG signal vs. 4 sps for RR series. This may be important, first of all, when analyzing the interaction of cardiac regulation processes with other periodic processes in the body, such as the activity of neural circuits in the brain.

Alkhawajah H.A., Alshami A.M., Albarrati A.M.

Background: The role of autonomic nervous system (ANS) modulation in chronic neck pain remains elusive. Transcutaneous vagus nerve stimulation (t-VNS) provides a novel, non-invasive means of potentially mitigating chronic neck pain. This study aimed to assess the effects of ANS modulation on heart rate variability (HRV), pain perception, and neck disability. Methods: In this double-blind randomized clinical trial, 102 participants with chronic neck pain were randomly allocated to one of three groups: t-VNS plus standard-care physiotherapy (SC-PT), heart rate variability biofeedback (HRV-BF) with SC-PT, or SC-PT alone. Interventions were administered three times weekly for 6 weeks. The following outcome measures were assessed at baseline and after 6 weeks: HRV, the visual analog scale (VAS), the pressure pain threshold (PPT), and the neck disability index (NDI). Results: The t-VNS group exhibited significant improvements compared to the HRV-BF and SC-PT groups. Specifically, t-VNS increased the RR interval (mean difference [MD] = 35.0 ms; p = 0.037) and decreased the average heart rate (MD = −5.4 bpm; p = 0.039). Additionally, t-VNS reduced the VAS scores (versus HRV-BF: MD = −0.8 cm, p = 0.044; SC-PT: MD = −0.9 cm, p = 0.018), increased the PPT (versus HRV-BF: MD = 94.4 kPa, p < 0.001; SC-PT (MD = 56.2 kPa, p = 0.001)), and lowered the NDI scores (versus HRV-BF: MD = −4.0, p = 0.015; SC-PT: MD = −5.9, p < 0.001). Conclusions: t-VNS demonstrated superior effectiveness compared to HRV-BF and SC-PT in regulating HRV, alleviating pain, and enhancing functional capabilities in individuals with chronic neck pain.

Zhu S., Pan W., Yao Y., Shi K.

Shekhar S., Kumar A., Sharma A.

For developing preordain capability in health care, it is important to understand the healthcare system. To achieve this demeanour, it is important to model the system mathematically and define the automata of the system. It is serendipitous that quantitative analysis of the major healthcare system can be done using the mathematical model of the healthcare system. This review paper discusses a few of the mathematical models. The paper is categorized into five sections. Section 1 discusses the pioneer work on the mathematical modelling of the heart which laid the foundation stone for the remaining works including model- and automata-based analysis of the heart and pacemaker. The second section discusses the parameters associated with the modelling of the heart and further extends onto the mathematical modelling which is followed by the aberrant heart conditions and use of pacemaker to control the conditions. The section further discusses one of the major concerns of health, i.e., increasing rate of cancer globally. Referring to the report of Global Cancer Observatory (GCO), an International Cancer Research Agency (WHO), there are 36 types of cancer reported from 185 countries worldwide, in 2020 which has also been published in American Cancer Society Journal. The proliferating rate of cancer needs to be correlated with the population. The third section discusses the model of change of population with the augmentation of the cancer cases. It also discusses the prediction of cancer cases in future for prescient vision and analysis and for initiating adaptive measures to control cancer.

Pintea C., Vlad R., Antonoaea P., Rédai E.M., Bîrsan M., Barabás E., Manea A., Pușcaș I.A., Ciurba A.

Background/Objectives: The search for novel ways of providing treatment also targets the development of formulations used in drug delivery. Among the important characteristics of pharmaceutical gels are their ability to penetrate membranes, their capability to offer rapid response, and their capacity to avoid the hepatic metabolization route followed by many drugs. Bigels combine the advantages of both hydrogels and oleogels, creating a biphasic system that might improve the solubility of amiodarone in water, which is otherwise poorly soluble. This study aimed to succeed in formulating stable amiodarone hydrochloride bigels (coded from ABG1-ABG6) destined for atrial application and evaluating them from a pharmacotechnical perspective. Methods: Three of the six initial formulations presented stability and underwent studies of spreadability, rheology, drug content, textural properties, and microbiological activity. A statistical analysis was performed on penetrometry and drug assay data. Results: The spreadability varied from 1734.07 mm2 (ABG1) to 2163.85 mm2 (ABG6), while the drug concentration ranged between 1.35 and 1.49% (w/w). The textural profile analysis highlighted superior hardness, cohesiveness, and resilience for ABG6 and higher adhesion for ABG2. Both presented pseudoplastic thixotropic behavior, while a plastic thixotropic flow was registered in the case of ABG1. Conclusions: All three bigels are suitable for amiodarone incorporation; however, the influence of the type of ingredients chosen on the texture and properties of the formulations was reflected in the data gathered upon evaluation.

Xu Y., Yu Y., Guo Z.

Cardiovascular disease remains the leading cause of global mortality. Current stem cell therapy and heart transplant therapy have limited long-term stability in cardiac function. Cardiac tissue engineering may be one of the key methods for regenerating damaged myocardial tissue. As an ideal scaffold material, hydrogel has become a viable tissue engineering therapy for the heart. Hydrogel can not only provide mechanical support for infarcted myocardium but also serve as a carrier for various drugs, bioactive factors, and cells to increase myocardial contractility and improve the cell microenvironment in the infarcted area, thereby improving cardiac function. This paper reviews the applications of hydrogels and biomedical mechanisms in cardiac tissue engineering and discusses the challenge of clinical transformation of hydrogel in cardiac tissue engineering, providing new strategies for treating cardiovascular diseases.

Kuzmichkina M.A., Kaveshnikov V.S.

The increasing volume of coronary artery bypass grafting inevitably contributes to a growing number of postoperative complications. Atrial fibrillation (AF) develops in every second or third patient. This complication prolongs inpatient stays and increases costs of the healthcare system. The review presents data on the risk factors for postoperative AF, as well as the proposed methods of prevention and treatment. The research results indicate the role of type 2 diabetes mellitus, obesity, arterial hypertension; among laboratory parameters, mean platelet volume, red blood cell distribution width, C-reactive protein, erythrocyte sedimentation rate, monocyte/high-density lipoprotein cholesterol ratio are of prognostic value. Drug and non-drug methods of prevention and treatment of postoperative AF are discussed. The methods indicated in the presented works showed effectiveness, but had a number of limitations.

Nasonov E.L., Drapkina O.M.

The main indications for colchicine treatment until recently were gout, pericarditis, familial Mediterranean fever and some other auto-inflammatory diseases. The expansion of indications (repositioning) for the use of colchicine in the direction of prevention of cardiovascular complications should be considered as one of the major events in medicine of the XXI century. Deciphering the role of inflammation as the most important mechanism for the development of atherosclerosis has created prerequisites for the development of the concept of anti-inflammatory therapy of atherosclerosis, in which low-dose colchicine therapy can take an important place, complementing the effects of aspirin, statins and antihypertensive therapy. The analysis of materials from randomized placebo-controlled studies of colchicine indicates a decrease in the frequency of cardiovascular complications in patients with coronary heart disease (by 31%) and in patients who have recently suffered a myocardial infarction (by 23%), as well as myocardial infarction (by 33%), stroke, the need for myocardial revascularization and cardiovascular mortality. The use of colchicine in a low dose (0.5 mg/day) is approved by the U.S. Food and Drug Administration for the prevention of cardiovascular complications in patients with coronary heart disease. It can be assumed that in the future colchicine will take an important place in the prevention and treatment of cardiovascular pathology associated with atherosclerotic vascular disease.

Rödel A., Fernandes Y., Brisolara J., De Carvalho J., Moresco R.

ABSTRACTIntroductionEstimating patient risk before heart surgery (HS) is crucial. Perioperative inflammation is associated with several complications and mortality. This study investigated blood cell count inflammatory indices (BCCII) to predict risks, including neutrophil‐to‐lymphocyte ratio (NLR), derivate NLR (DNLR), neutrophil‐to‐platelet‐lymphocyte ratio (NLPR), lymphocyte‐to‐monocyte ratio, platelet‐to‐lymphocyte ratio (PLR), Systemic Inflammatory Index (SII), Systemic Inflammatory Reaction Index (SIRI), and Aggregate Index of Systemic Inflammation (AISI).MethodsData from a cohort of patients undergoing on‐pump HS at a single center in Brazil were retrospectively analyzed. Data were obtained from medical records and a laboratory analyzer, and SPSS version 20.0 was used for index calculations and statistical analyses.ResultsIn total, 444 surgeries were performed, and 40 in‐hospital deaths occurred. Except for PLR, all other indexes were independent predictors of death after multivariate adjustment (all p < 0.05). Discrimination performance was absent for PLR and AISI, and NLR, NLPR, and DNLR demonstrated the best area under the receiver operating characteristic curve (AUC > 0.7; all p < 0.0001). For survivors (n = 404), all indexes exhibited a correlation with the length of hospital stay (all p < 0.03), and NLR, NLPR, and DNLR were predictors (p < 0.026) of poor operative outcomes (acute myocardial infarction, cerebrovascular attack, cardiac arrest, low cardiac output, prolonged mechanical ventilation, renal failure, and sepsis).ConclusionsAll BCCII scores were associated with length of hospital stay. Apart from PLR, all indexes were independent predictors of in‐hospital mortality. Accuracy was highest for NLR, NLPR, and DNLR; for survivors, these three factors were good predictors of poor operative outcomes.

Avdeev S.N., Barbarash O.L., Valieva Z.S., Volkov A.V., Veselova T.N., Galyavich A.S., Goncharova N.S., Gorbachevsky S.V., Gramovich V.V., Danilov N.M., Klimenko A.A., Martynyuk T.V., Moiseeva O.M., Ryzhkova D.V., Simakova M.A., et. al.

The Russian Society of Cardiology (RSC)With the participation of: the Russian Association of Cardiovascular Surgeons, Eurasian Association of Cardiology (EAC), The Russian Medical Society on Arterial Hypertension (RMSAH), Russian Respiratory Society (RRS), the Association of Anesthesiologists and Intensive Care Specialists, the Russian Society of Radiologists and Radiologists (RSRR), the Association of Rheumatologists of Russia.Endorsed by the Research and Practical Council of the Ministry of Health of the Russian Federation (12.09.2024).

Drăgan A., Drăgan A.Ş., Ştiru O.

Objectives: The role of inflammation in the pathophysiology of atherosclerosis is extensive. Our study aims to assess the predictive role of inflammatory indexes regarding in-hospital mortality in major vascular surgery of Leriche syndrome as a convenient, low-cost, and noninvasive prognostic marker to optimize the patient’s perioperative course. Methods: Our retrospective single-center study enrolled consecutive patients diagnosed with aortoiliac occlusive disease, Leriche syndrome, who underwent elective major vascular surgery between 2017 and 2023 in a tertiary cardiovascular center. Preoperative, postoperative, and day-one after-surgery data, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio, and monocyte–lymphocyte ratio, were studied to the endpoint, in-hospital death. We also tested the delta values of the indexes to the endpoint. The indexes were compared to the Revised Cardiac Risk Index (RCRI) and Vascular Surgery Group Cardiac Risk Index (VSG-CRI) for outcome prediction. Results: The tested inflammatory indexes significantly increased from the preoperative to postoperative and, further, to the day-one settings. Preoperative AISI (p = 0.040) emerged as the only independent risk factor regarding in-hospital death occurrence in Leriche patients who underwent major revascularization surgery. While RCRI did not significantly predict the endpoint (AUC = 0.698, p = 0.057), VSG-CRI (AUC = 0.864, p = 0.001) presented the best result in ROC analysis. Postoperative NLR (AUC = 0.758, p = 0.006) was next, followed by NLR postoperative–preoperative (_Preop-_Postop) delta value (AUC = 0.725, p = 0.004), postoperative SIRI (AUC = 0.716, p = 0.016), SIRI_Preop-_Postop delta value (AUC = 0.712, p = 0.016), postoperative SII (AUC = 0.692, p = 0.032), and SII_Preop-_Postop delta value (AUC = 0.631, p = 0.030). Conclusions: Inflammatory indexes are valuable tools for assessing perioperative risk in major vascular surgery, enhancing the value of the already validated risk scores.

Yan Q., Liu G., Wang R., Li D., Chen X., Cong J., Wang D.

Giannino G., Nocera L., Andolfatto M., Braia V., Giacobbe F., Bruno F., Saglietto A., Angelini F., De Filippo O., D’Ascenzo F., De Ferrari G.M., Dusi V.

AbstractThe identification of acute cardioprotective strategies against myocardial ischemia/reperfusion (I/R) injury that can be applied in the catheterization room is currently an unmet clinical need and several interventions evaluated in the past at the pre-clinical level have failed in translation. Autonomic imbalance, sustained by an abnormal afferent signalling, is a key component of I/R injury. Accordingly, there is a strong rationale for neuromodulation strategies, aimed at reducing sympathetic activity and/or increasing vagal tone, in this setting. In this review we focus on cervical vagal nerve stimulation (cVNS) and on transcutaneous auricular vagus nerve stimulation (taVNS); the latest has the potential to overcome several of the issues of invasive cVNS, including the possibility of being used in an acute setting, while retaining its beneficial effects. First, we discuss the pathophysiology of I/R injury, that is mostly a consequence of the overproduction of reactive oxygen species. Second, we describe the functional anatomy of the parasympathetic branch of the autonomic nervous system and the most relevant principles of bioelectronic medicine applied to electrical vagal modulation, with a particular focus on taVNS. Then, we provide a detailed and comprehensive summary of the most relevant pre-clinical studies of invasive and non-invasive VNS that support its strong cardioprotective effect whenever there is an acute or chronic cardiac injury and specifically in the setting of myocardial I/R injury. The potential benefit in the emerging field of post cardiac arrest syndrome (PCAS) is also mentioned. Indeed, electrical cVNS has a strong anti-adrenergic, anti-inflammatory, antioxidants, anti-apoptotic and pro-angiogenic effect; most of the involved molecular pathways were already directly confirmed to take place at the cardiac level for taVNS. Pre-clinical data clearly show that the sooner VNS is applied, the better the outcome, with the possibility of a marked infarct size reduction and almost complete left ventricular reverse remodelling when VNS is applied immediately before and during reperfusion. Finally, we describe in detail the limited but very promising clinical experience of taVNS in I/R injury available so far.

Yalçin F., Abraham M.R., Garcia M.J.

Myocardial remodeling is developed by increased stress in acute or chronic pathophysiologies. Stressed heart morphology (SHM) is a new description representing basal septal hypertrophy (BSH) caused by emotional stress and chronic stress due to increased afterload in hypertension. Acute stress cardiomyopathy (ASC) and hypertension could be together in clinical practice. Therefore, there are some geometric and functional aspects regarding this specific location, septal base under acute and chronic stress stimuli. The findings by our and the other research groups support that hypertension-mediated myocardial involvement could be pre-existed in ASC cases. Beyond a frequently seen predominant base, hyperkinetic tissue response is detected in both hypertension and ASC. Furthermore, hypertension is the responsible factor in recurrent ASC. The most supportive prospective finding is BSH in which a hypercontractile base takes a longer time to exist morphologically than an acutely developed syndrome under both physiologic exercise and pressure overload by transaortic binding in small animals using microimaging. However, cardiac decompensation with apical ballooning could mask the possible underlying hypertensive disease. In fact, enough time for the assessment of previous hypertension history or segmental analysis could not be provided in an emergency unit, since ASC is accepted as an acute coronary syndrome during an acute episode. Additional supportive findings for SHM are increased stress scores in hypertensive BSH and the existence of similar tissue aspects in excessive sympathetic overdrive like pheochromocytoma which could result in both hypertensive disease and ASC. Exercise hypertension as the typical form of blood pressure variability is the sum of physiologic exercise and pathologic increased blood pressure and results in increased mortality. Hypertension is not rare in patients with a high stress score and leads to repetitive attacks in ASC supporting the important role of an emotional component as well as the potential danger due to multiple stressors at the same time. In the current review, the impact of multiple stressors on segmental or global myocardial remodeling and the hazardous potential of multiple stressors at the same time are discussed. As a result, incidentally determined segmental remodeling could be recalled in patients with multiple stressors and contribute to the early and combined management of both hypertension and chronic stress in the prevention of global remodeling and heart failure.

Dusi V., Angelini F., De Ferrari G.M.

Hadaya J., Dajani A., Cha S., Hanna P., Challita R., Hoover D.B., Ajijola O.A., Shivkumar K., Ardell J.L.

This study sought to evaluate the impact of chronic vagal nerve stimulation (cVNS) on cardiac and extracardiac neural structure/function after myocardial infarction (MI). Groups were control, MI, and MI + cVNS; cVNS was started 2 days post-MI. Terminal experiments were performed 6 weeks post-MI. MI impaired left ventricular mechanical function, evoked anisotropic electrical conduction, increased susceptibility to ventricular tachycardia and fibrillation, and altered neuronal and glial phenotypes in the stellate and dorsal root ganglia, including glial activation. cVNS improved cardiac mechanical function and reduced ventricular tachycardia/ventricular fibrillation post-MI, partly by stabilizing activation/repolarization in the border zone. MI-associated extracardiac neural remodeling, particularly glial activation, was mitigated with cVNS.

Wu Z., Liao J., Liu Q., Zhou S., Chen M.

Autonomic imbalance between the sympathetic and parasympathetic nervous systems contributes to the progression of chronic heart failure (HF). Preclinical studies have demonstrated that various neuromodulation strategies may exert beneficial cardioprotective effects in preclinical models of HF. Based on these encouraging experimental data, vagus nerve stimulation (VNS) has been assessed in patients with HF with a reduced ejection fraction. Nevertheless, the main trials conducted thus far have yielded conflicting findings, questioning the clinical efficacy of VNS in this context. This review will therefore focus on the role of the autonomic nervous system in HF pathophysiology and VNS therapy, highlighting the potential reasons behind the discrepancy between preclinical and clinical studies.

Fetisova V.I., Namitokov A.M., Gilevich I.V., Kosmacheva E.D.

Many prognostic tools have been developed over the past decades, however, the identification of biomarkers that can predict the risk of acute coronary disease and its associated complications, especially heart failure, remains a promising direction, the study of which will provide understanding of the pathophysiology of this disease and identify new targets for therapy. One such potential biomarker is soluble suppression of tumorigenicity 2, which is able not only to predict left ventricular remodeling and poor clinical outcome among patients with acute coronary syndrome, but also to complement other well-established cardiac biomarkers such as natriuretic peptides and cardiac troponins. At the same time, if a number of separate but often converging pathways are involved in the pathogenesis of acute coronary disease, then multimarker approaches with various combinations of new cardiac biomarkers and their continuous assessment are likely to improve the prediction of cardiac risk and long-term outcomes.

Ezhov M.V., Kukharchuk V.V., Sergienko I.V., Alieva A.S., Antsiferov M.B., Ansheles A.A., Arabidze G.G., Aronov D.M., Arutyunov G.P., Akhmedzhanov N.M., Balakhonova T.V., Barbarash O.L., Boytsov S.A., Bubnova M.G., Voevoda M.I., et. al.

The Russian Society of Cardiology (RKO)With the participation of: The National Society for the Study of Atherosclerosis (NOA), the Russian Association of Endocrinologists (RAE), the Russian Society of Cardiosomatic Rehabilitation and Secondary Prevention (RosOKR), the Russian Scientific Medical Society of Therapists (RNMOT), the Eurasian Association of Cardiologists, the Eurasian Association of Therapists (EAT), the Russian Association of Gerontologists and Geriatricians

Zhao Z., Pan Z., Wu C., Tian J., Qin J., Zhang Y., Jin X.

BackgroundCoarctation of the aorta (CoA), is a congenital malformation, often combined with several cardiac abnormalities. At present, the operation effect is satisfactory, but postoperative restenosis is still a matter. Identification of risk factors for restenosis and prompt therapy adjustments may improve patient outcomes.Materials and methodsA retrospective clinical study of patients under 12 who had CoA repair in 2012–2021, with a randomized cohort population of 475 patients.ResultsA total of 51 patients (M/F: 30/21) with a mean age of 5.33 (2.00–15.00) months and a median weight of 5.60 (4.20–10.00) kg. The mean follow-up was 8.93 (3.77–19.37) months. Patients were divided into 2 groups: no-restenosis (n-reCoA) (G1, 38 patients) and restenosis (reCoA) (G2, 13 patients). ReCoA was defined as a restenosis requiring interventional or surgery or a pressure gradient &gt;20 mmHg at the repair site as reported by B-ultrasound with the presence of an upper and lower limb blood pressure gradient or growing dysplasia. The overall reCoA incidence was 25% (13/51). In multivariate COX regression, smaller preoperative z-score of the ascending aorta (P = 0.009, HR = 0.68) and transverse aortic arch (P = 0.015, HR = 0.66), arm-leg systolic pressure gradient ≥12.5 mmHg at discharge (P = 0.003, HR = 1.09) were independent risk factors for reCoA.ConclusionThe overall outcome of CoA surgery is successful. Smaller preoperative z-score of the ascending aorta and transverse aortic arch, and an arm-leg systolic pressure gradient ≥12.5 mmHg at discharge increase reCoA risk, and closer follow-up for such patients are required especially within 1 postoperative year.

Simon T., Kirk J., Dolezalova N., Guyot M., Panzolini C., Bondue A., Lavergne J., Hugues S., Hypolite N., Saeb-Parsy K., Perkins J., Macia E., Sridhar A., Vervoordeldonk M.J., Glaichenhaus N., et. al.

The magnitude of innate inflammatory immune responses is dependent on interactions between peripheral neural and immune cells. In particular, a cholinergic anti-inflammatory pathway (CAP) has been identified in the spleen whereby noradrenaline (NA) released by splenic nerves binds to ß2-adrenergic receptors (β2-AR) on CD4+ T cells which, in turn, release acetylcholine (ACh). The binding of ACh to α7 acetylcholine receptors (α7-AChR) expressed by splenic macrophages inhibits the production of inflammatory cytokines, including tumor necrosis factor (TNF). However, the role of ACh-secreting CD4+ T-cells in the CAP is still controversial and largely based on the absence of this anti-inflammatory pathway in mice lacking T-cells (nude, FoxN1−/−). Using four conscious, non-lymphopenic transgenic mouse models, we found that, rather than acting on CD4+ T-cells, NA released by splenic nerve terminals acts directly onto β2-AR on splenic myeloid cells to exert this anti-inflammatory effect. We also show that, while larger doses of LPS are needed to trigger CAP in nude mouse strain compared to other strains, TNF production can be inhibited in these animals lacking CD4+ T-cell by stimulating either the vagus or the splenic nerve. We demonstrate that CD4+ T-cells are dispensable for the CAP after antibody-mediated CD4+ T-cell depletion in wild type mice. Furthermore, we found that NA-mediated inhibition of in vitro LPS-induced TNF secretion by human or porcine splenocytes does not require α7-AChR signaling. Altogether our data demonstrate that activation of the CAP by stimulation of vagus or splenic nerves in mice is mainly mediated by direct binding of NA to β2-AR on splenic macrophages, and suggest that the same mechanism is at play in larger species.

Dimagli A., Soletti G., Harik L., Perezgrovas Olaria R., Cancelli G., An K.R., Alzghari T., Mack C., Gaudino M.

Coronary artery bypass grafting is the most commonly performed cardiac surgical procedure. Conduit selection is crucial to achieving early optimal outcomes, with graft patency being likely the main driver to long-term survival. We present a review of current evidence on the patency of arterial and venous bypass conduits and of differences in angiographic outcomes.

Joshi A., Bhambhani A., Barure R., Gonuguntla S., Sarathi V., Attia A.M., Shrestha A.B., Jaiswal V.

Xia Y., Xia C., Wu L., Li Z., Li H., Zhang J.

Background and aim: Chronic low-grade inflammation is associated with various health outcomes, including cardiovascular diseases (CVDs) and cancers. Systemic immune inflammation index (SII) and system inflammation response index (SIRI) have lately been explored as novel prognostic markers for all-cause mortality and cardiovascular mortality. However, studies on prediction value in nationwide representative population are scarce, which limit their generalization. To bridge the knowledge gap, this study aims to prospectively assess the association of SII, SIRI with all-cause mortality and cardiovascular mortality in the National Health and Nutrition Examination Survey (NHANES). Methods: From 1999 to 2018, 42,875 adults who were free of pregnancy, CVDs (stroke, acute coronary syndrome), cancers, and had follow-up records and participated in the NHANES were included in this study. SII and SIRI were quantified by calculating the composite inflammation indicators from the blood routine. To explore the characteristics of the population in different SII or SIRI levels, we divided them according to the quartile of SII or SIRI. The associations between SII, SIRI, and all-cause mortality and cardiovascular mortality events were examined using a Cox regression model. To investigate whether there was a reliable relationship between these two indices and mortalities, we performed subgroup analysis based on sex and age. Results: A total of 42,875 eligible individuals were enrolled, with a mean age of 44 ± 18 years old. During the follow-up period of up to 20 years, 4250 deaths occurred, including 998 deaths from CVDs. Cox proportional hazards modeling showed that adults with SII levels of >655.56 had higher all-cause mortality (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.18–1.41) and cardiovascular mortality (HR, 1.33; 95% CI, 1.11–1.59) than those with SII levels of <335.36. Adults with SIRI levels of >1.43 had higher risk of all-cause (HR, 1.39; 95% CI, 1.26–1.52) and cardiovascular death (HR, 1.39; 95% CI, 1.14–1.68) than those with SIRI levels of <0.68. In general population older than 60 years, the elevation of SII or SIRI was associated with the risk of all-cause death. Conclusion: Two novel inflammatory composite indices, SII and SIRI, were closely associated with cardiovascular death and all-cause death, and more attention should be paid to systemic inflammation to provide better preventive strategies.

Drapkina O.M., Dzhioeva O.N., Rogozhkina E.A., Shvarts E.N., Kiselev A.R.

The article provides an overview of key studies on vagus nerve stimulation. The vagus nerve stimulation method affects the nerve fibers of the internal and external nerve plexuses, enhancing the parasympathetic effect. The positive therapeutic effect has been achieved in various experimental and clinical studies on the treatment of neurological and cardiac diseases, metabolic syndrome, and obesity. It has been shown that vagus nerve stimulation reduces epileptic seizures frequency, cardiac arrhythmias, and is prognostically favorable for the treatment of ischemia and reperfusion injury of the myocardium. Recent studies have examined the inflammatory reflex involved in the pathogenesis of obesity. The role of bioelectronic vagus nerve stimulation is being actively investigated for the treatment of obesity and metabolic syndrome.

Jemielity M., Gładki M., Olasińska-Wiśniewska A., Urbanowicz T.

The inflammatory background of coronary artery disease is gaining more attention in recent times.Off pump surgery is minimally invasive type of surgical revascularization with relatively low number of applications in cardiac surgery centers worldwide that allows for perioperative inflammatory reactions minimalization.The simple inflammatory markers (neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelets to lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), aggregate index of systemic inflammation (AISI)) possess a clinically significant impact on patients' prognosis and may help to improve patients' long-term results.The review presents the current knowledge regarding their utility in clinical practice.Assessment of inflammatory indices obtained from whole blood count analysis allows to indicate those patients who need scrupulous follow-up due to predicted worse long-term survival.Perioperative measurement and analysis of simple whole blood counts is inexpensive and easily available and may improve the results of surgical revascularization by better identification of patients at higher risk of worse outcomes.

Kiselev A.R., Schwartz E.N., Dzhioeva O.N., Drapkina O.M.

Пандемия ожирения становится все более актуальной проблемой современной медицины, обусловливая необходимость развития новых подходов к коррекции избыточной массы тела. К таковым относится электрическая стимуляция блуждающего нерва, возможности клинического применения которой активно изучают во всем мире. В обзоре обсуждаются современные представления о физиологических основах коррекции избыточной массы тела с использованием чрескожной стимуляции блуждающего нерва.