Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

ПРОТЕЗИРОВАНИЕ АОРТАЛЬНОГО КЛАПАНА АУТОПЕРИКАРДОМ БЕЗ ИСПОЛЬЗОВАНИЯ ШАБЛОНОВ: НЕПОСРЕДСТВЕННЫЕ И СРЕДНЕОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ

HighlightsWe have described the outcomes of aortic valve replacement using autologous pericardium without special templates. Although S. Ozaki is considered by many to be the founder of neocuspidization technique, the methods for sizing of the neocusps were proposed long before him. The method of the Japanese professor involves using special templates. This article presents a mathematical formula to calculate neocusps` size, which significantly simplifies the procedure, and makes it possible to perform it in centers that do not possess Ozaki templates. Abstract Aim: To describe an original technique of aortic valve replacement using autologous pericardium without templates. The calculation of the neocusps` size is based on the diameter of aortic annulus, which can be estimated both intraoperatively and preoperatively, helps to reduce the duration of surgery, CPB time and myocardial ischemia, and lower the rates of late complications.Methods: The prospective study included 34 patients with aortic valve disease admitted to the Cardiac Surgical Department of the University Clinical Hospital No.1 of the First Moscow State Medical University named after I.M. Sechenov, Ministry of Health of Russia in the period from January 2020 to March 2023. The mean age of the patients was 51±17 years (from 19 to 78 years). Gender distribution in the total group was as follows: male 50% (n = 17), female 50% (n = 17). All patients underwent aortic valve replacement using autologous pericardium without templates (by calculating the neocusps` size). Isolated aortic valve replacement was performed in 17 patients (50%), ascending aorta replacement in 11 patients (32.3%), mitral valve intervention in 5 (14.7%), coronary artery bypass grafting in 3 (8.8%) cases. 11 patients (32.3%) had aortic valve stenosis, 4 patients (11.7%) had insufficiency, and 19 patients (55.8%) had both stenosis and insufficiency. Bicuspid aortic valve was detected in 18 patients (52.9%). All patients were divided into two groups: Komarov (aortic valve replacement only) and Komarov Plus (aortic valve replacement and treatment for concomitant cardiac pathology).Results: There were no cases of conversion to traditional aortic valve replacement using prosthetic valves. There were 2 cases of in-hospital mortality; according to medical records, death in both cases was due to complications provoked by double pneumonia caused by SARS-CoV-2. 1 patient required reoperation 4 months after the intervention due endocarditis caused by Streptococcus viridans. In the midterm follow-up period, hemodynamic parameters such as peak gradient, mean gradient, and peak velocity were 11.96±4.70 mm Hg, 5.88±2.07 mm Hg, 168.19±30.56 mm Hg.Conclusions: The obtained valve prosthesis is anatomically analogous to the native valve and provides reliable peak pressure reduction, no postoperative regurgitation, and increased effective orifice area. The proposed method is safe and can serve as an alternative to the Ozaki procedure, in which the neocusps are outlined using special templates.Основные положения Продемонстрированы результаты протезирования аортального клапана аутоперикардом без использования шаблонов. Родоначальником неокуспидизации принято считать S. Ozaki, однако методы расчета неостворки из перикарда предложены задолго до него. Методика японского профессора заключается в использовании специальных шаблонов. В данной статье представлен математический расчет створки, выполненный хирургами Сеченовского Университета, позволяющий не только существенно упростить процедуру, но и выполнять ее в тех центрах, где шаблонов Ozaki нет. Резюме Цель: Описана оригинальная методика полной реконструкции аортального клапана аутоперикардом. Расчет формы неостворок осуществлен на основании данных о диаметре фиброзного кольца, которые могут быть получены как во время, так и до операции, что позволяет сократить время вмешательства, искусственного кровообращения и ишемии миокарда, а в конечном итоге добиться снижения ишемии головного мозга и снизить вероятность поздних осложнений.Материалы и методы: Проведено проспективное исследование 34 пациентов, оперированных по поводу порока аортального клапана в кардиохирургическом отделении Университетской клинической больницы № 1 ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет) в период с января 2020 г. по март 2023 г. Средний период наблюдения для всей когорты составил 14,1±7,7 мес. Средний возраст больных – 51±17 лет (19–78 лет). Гендерное распределение в общей группе: мужской пол – 50% (n = 17), женский – 50% (n = 17). Всем пациентам выполнено протезирование аортального клапана аутоперикардом без использования шаблонов (расчетным способом). 17 (50%) больным проведена изолированная коррекция порока аортального клапана, 11 (32,3%) – протезирование восходящей аорты, 5 (14,7%) – вмешательство на митральном клапане, в 3 (8,8%) случаях выполнено коронарное шунтирование. Стеноз аортального клапана отмечен у 11 (32,3%) пациентов, недостаточность – у 4 (11,7%), стеноз и недостаточность – у 19 (55,8%). Двустворчатый аортальный клапан выявлен у 18 (52,9%) больных. Все пациенты разделены на две группы: Komarov (изолированная коррекция порока аортального клапана) и Komarov Plus (коррекция порока аортального клапана с сопутствующей кардиальной патологией).Результаты: Не зарегистрировано случаев конверсии в стандартное протезирование аортального клапана. Зафиксировано два случая госпитальной летальности; по данным патологоанатомического заключения, смерть в обоих случаях наступила из-за осложнений, спровоцированных двусторонней полисегментарной пневмонией, вызванной SARS-CoV-2. Одному пациенту через 4 мес. после вмешательства потребовалась повторная операция вследствие развившегося эндокардита, возбудитель Streptococcus viridans. В среднеотдаленном периоде гемодинамические показатели, такие как пиковый градиент, средний градиент и пиковая скорость, составили 11,96±4,70, 5,88±2,07 мм рт. ст. и 168,19±30,56 см/с.Заключение: Конечный вид протеза служит анатомическим аналогом нативного клапана и обеспечивает достоверное снижение пикового давления, отсутствие регургитации на клапане после операции и увеличение площади эффективного отверстия. Данный метод можно рассматривать как безопасную альтернативу процедуре Ozaki, при которой створки выкраивают с помощью специальных шаблонов

Intermittent hypoxic preconditioning reduces the risk of peri- and postoperative complications during on-pump cardiac surgery

Aim. To assess the effect of intermittent hypoxic-hyperoxic exposures (IHHE) on the outcomes of on-pump cardiac surgery.Material and methods. This prospective, single-center, randomized, controlled study was conducted in 110 patients with heart valve defects and/or aortic pathology from the cardiac surgery clinic of the I. M. Sechenov First Moscow State Medical University. The total sample was randomly divided into a group of patients who underwent IHHE (n=66) and a control group of patients who underwent placebo procedures with ambient air (n=44). The frequency and structure of intra-and postoperative complications were analyzed within 30 days after surgery. The presence of cognitive impairment, as well as serum troponin I and lactate concentrations were analyzed before and after surgery.Results. Peri- and early postoperative complications such as cardiac death, non-fatal infarction and acute heart failure occurred significantly less frequently in patients treated with IHHE compared with placebo group (1,6% vs 16,7%, p=0,009; 1,6% vs 16,7%, p=0,009; 6,3% vs 33,3%, p<0,001, respectively). The median troponin I values 24 hours after surgery were 1,068 ng/ml (0,388-1,397 ng/ml) in the IHHE group and were significantly lower compared to the control group (1,980 ng/ml (1,068-3,239 ng/ml)). The serum lactate level after surgery was 1,8±0,7 mmol/l in the IHHE group and was significantly lower compared to the control group — 2,4±1,2 (p=0,05). Cognitive function, assessed by MOCA and MMSE tests, turned out to be significantly higher in patients who underwent a preoperative IHHE. No significant complications or serious adverse events were observed during the IHHE procedures.Conclusion. The use of individually adapted hypoxic preconditioning procedures reduces the incidence of peri- and postoperative complications, which is accompanied by a lower ischemia-reperfusion myocardial injury during artificial circulation with preservation of cognitive functions. IHHE procedures ramp up prehabilitation of patients referred for on-pump surgery of heart defects and aortic pathology

Возможности портативного регистратора электрокардиограммы и пульсовой волны в выявлении систолической дисфункции левого желудочка

Highlights. The article presents a novel and unique method for assessment of left ventricular systolic disfunction using electrocardiography and photoplethysmography data. This method will improve and simplify the detection of cardiovascular diseases.Aim. To evaluate left ventricular (LV) systolic function using electrocardiogram (ECG) and photoplethysmogram (PPG) signals recorded by a single-channel ECG and PPG-based monitor.Methods. The prospective study included 489 patients over 18 years old with various cardiovascular diseases. All participants underwent echocardiography to determine the main indicators of LV systolic function: LV ejection fraction (EF), LV outflow tract velocity time integral (LVOT VTI), and global longitudinal strain (GLS). Moreover, all patients underwent 1-lead ECG and PPG recording using a single-channel ECG and PPG-based monitor (CardioQvark). The obtained data were analyzed, and ROC curve analysis was performed.Results. We have identified ECG and PPG parameters associated with a decrease in LV contractile function. During the analysis, the ECG, T-wave amplitude (TA) and RonsF parameters showed the highest diagnostic accuracy. With EF below 55%, the area under the ROC curve (AUC) was 0.822, sensitivity (Se) 80%, specificity (Sp) 69% in EF below 55% in TA; in RonsF AUC was 0.743, Se 81%, Sp 77%. With EF below 40%, AUC was 0.915, Se 85%, Sp 83% in TA, and in RonsF AUC was 0.844, Se 82%, Sp 82%. Diagnostic accuracy of ECG signals in case of LVOT VTI lower than 16 cm was measured: TA (AUC 0.755, Se 82%, Sp 70%), RonsF (AUC 0.620, Se 77%, Sp 72%). PPG signals were not significantly associated with reduced EF; however, the pulse wave parameters were associated with lower LVOT VTI: in DP-B0 AUC was 0.687, Se 71%, Sp 74%. The combination of ECG and PPG signals was significantly associated with EF below 40% (RonsF * DP-SEP (AUC 0.877, Se 86%, Sp 85%). ECG and PPG signals were not associated with LV GLS.Conclusion. Assessment of LV systolic function can be performed by analyzing ECG and PPG signals recorded using a portable single-channel CardioQvark monitor.Основные положения. Описана возможность диагностики снижения систолической функции левого желудочка по данным электро- и фотоплетизмограммы. Разработка метода оценки систолической функции левого желудочка на основе электро- и фотоплетизмограммы позволит улучшить и упростить выявление сердечно-сосудистых заболеваний. Метод оценки систолической функции сердца, изложенный в исследовании, представлен впервые и является уникальным.Цель. Оценка систолической функции левого желудочка (ЛЖ) на основе параметров электро- (ЭКГ) и фотоплетизмограммы (ФПГ), зарегистрированных одноканальным монитором ЭКГ с функцией фотоплетизмографии.Материалы и методы. В проспективное исследование включено 489 пациентов в возрасте старше 18 лет, имеющих заболевания сердечно-сосудистой системы. Всем участникам исследования выполнена эхокардиография с определением основных показателей систолической функции ЛЖ: фракции выброса (ФВ) ЛЖ, интеграла линейной скорости кровотока в выносящем тракте ЛЖ (VTI в ВТЛЖ), глобальной деформации ЛЖ (GLS). Также всем больным проведена регистрация ЭКГ в I отведении и ФПГ с использованием монитора ЭКГ с функцией фотоплетизмографии (CardioQVARK). Проведены расчет всех полученных параметров, затем ROC-анализ данных.Результаты. Выявлены параметры ЭКГ и ФПГ, ассоциированные со снижением сократительной функции ЛЖ. При анализе ЭКГ параметры TA (амплитуда T-волны) и RonsF (частота максимальной энергии переднего фронта R-волны) имели наибольшую диагностическую точность. При ФВ менее 55% для TA площадь под ROC-кривой (AUC) составила 0,822, чувствительность (Se) 80%, специфичность (Sp) 69%, а для параметра RonsF – AUC 0,743, Se 81%, Sp 77%. При ФВ менее 40%: AUC для TA составила 0,915, Se 85%, Sp 83%, для RonsF – AUC 0,844, Se 82%, Sp 82%. Диагностическая точность параметров ЭКГ при снижении VTI в ВТЛЖ менее 16 см: TA (AUC 0,755, Se 82%, Sp 70%), RonsF (AUC 0,620, Se 77%, Sp 72%). При оценке параметров ФПГ достоверной взаимосвязи со снижением ФВ не выявлено, однако параметры пульсовой волны ассоциированы с уменьшением VTI в ВТЛЖ: для DP-B0 AUC 0,687, Se 71%, Sp 74%. Комбинации параметров ЭКГ и ФПГ достоверно взаимосвязаны со значением ФВ менее 40% (RonsF*DP-SEP (AUC 0,877, Se 86%, Sp 85%)). Взаимосвязи параметров ЭКГ и ФПГ со значением GLS ЛЖ не обнаружено.Заключение. Определение систолической функции ЛЖ возможно при анализе параметров ЭКГ и ФПГ, зарегистрированных с помощью портативного одноканального монитора CardioQVARK

Determination of left ventricular diastolic dysfunction using machine learning methods

Abstract Introduction Nowadays, more than 50% of new cases of heart failure (HF) are due to heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction of left ventricular underlies the development of HFpEF. Determination of diastolic function can be determinated using echocardiographic examination but not as a method of screening. Purpose Create a Machine Learning model to determinate severe (2nd or 3rd degrees) left ventricular diastolic dysfunction (LV DD) using single channel ECG. Methods The study prospectively included 375 patients aged between 18 and 88 years. Each of them underwent an assessment of left ventricular diastolic function using echocardiography based on ASE/EACVI guidelines and standard 2016. ECG was registered in I standard lead for 3 minutes. Then a spectral analysis of the ECG was performed using a wavelet transform based on the Fourier transform. Prediction of LV DD was implemented based on different machine learning methods. Results Based on the time intervals between the waves, the energy of the ECG signal in the target zones of the complexes, the amplitude at different points of the ECG complexes and the asymmetry indicators, different mathematical models were created to determine the severe (2nd or 3rd degree) LV DD. Lasso regression predicted the presence of severe LV DD with sensitivity 90% and specificity 80,6% (AUC- 0.856). The most significant for this method were the following variables: TA, SDNN, RonsF, ASEPMAX, B1, TpTe, ADP, SEPMAX, Sbeta, SEPF, RR, SRP-B0, Pan.1, QT/TQ, PpeakN, SA, SRP-B1. Random Forest also showed high sensitivity 80% and specificity 89, 3% (AUC- 0.860). For Random Forest model the most dignificant were: TpTe, VAT, QTc, QT/TQ, J80A, TA, Tenergy, Tpenergy, Beta, QRS11energy, Pan, Pan.1, RA, Pfi, QRSst, QRSfi, PpeakP, PpeakN, Rpeak, Speak, RonsF, B0-B1, SEP, SEP-B1, SEP-B0, SRP, SRP-B1, SRP-B0, ASEP. LV DD 1 degree did not have markers in our study. Conclusion Several machine learning methods have shown high sensitivity and specificity in identifying severe LV DD. Potentially ECG can be used as a screening method for determination of the LV DD. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This work was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare” No. 075-15-2020-926 </jats:sec

Evaluation of the effects of interval hypoxic-hyperoxic training in patients with metabolic syndrome

Abstract Introduction Metabolic syndrome (MS) as a “cluster” of interrelated disorders, including insulin resistance, visceral obesity, dyslipidemia, and hypertension, is an serious clinical problem that is a high risk factor for the development of type 2 diabetes, acceleration of the development and progression of cardiovascular diseases, and such increasingly common liver damage like non-alcoholic fatty liver disease. According to a number of authors, metabolic syndrome is a reversible condition, and with early diagnosis and treatment, a reduction in the severity of manifestations of this syndrome can be achieved. A significant role in the treatment of MS and obesity is played by non-drug methods – dosed physical activity, diet, various physiotherapeutic procedures, as well as interval hypoxic-hyperoxic training (IHHT). Objective Evaluation of the effect of interval hypoxic-hyperoxic training (IHHT) on the components of metabolic syndrome, and the possibility of their reversal recovery. Materials and methods The study included 65 patients (33 men) with metabolic syndrome, aged 29–66 years. The patients were divided into 2 groups: study and control (the groups were matched by sex, age, presence of MS components and number of comorbidities). Initially, anthropometric, laboratory and instrumental studies were carried out. The patients of the main group underwent a course of IHHT for 3 weeks, 5 days a week (15 workouts). Patients in the control group underwent a course of training simulating IHHT (placebo), which also consisted of 15 trainings. The duration of one procedure was 40 minutes. Next day after the end of the training course, the changes in all initial parameters were assessed. Results The statistical significance of changes after the IGGT course was assessed using the Wilcoxon test as p&amp;lt;0.05 and was detected in the main group according to the following parameters: reduction in arterial stiffness, measured using CAVI (Cardio-Ankle Vascular Index, on the Fukuda Denshi ap.), a decrease in the stage of liver fibrosis and stiffness of liver tissue (was realized by a non-invasive method, a liver elastometry, on the FibroScan ap. Echosense), a decrease in high-sensitivity C-reactive protein, heat shot protein-70, a decrease in total cholesterol, low density lipoproteins, triglycerides levels. According to nitric oxide, transforming growth factor beta-1, heart-type fatty acid binding protein, there was no significant dynamics after the IHHT course in both groups. There was also a tendency towards a decrease in the indices of the abdominal/hip circumference, weight, and in blood pressure, but this results was not statistically significant, due to the insufficient power of the study (a small number of patients). Conclusions IHHT is a safe, well-tolerated procedure and is recommended in the therapeutic and prophylactic plan for patients with metabolic syndrome, and is effective in correcting and minimizing the components of this syndrome. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare” </jats:sec

Possibilities of a portable electrocardiogram and pulse wave recorder in detecting left ventricular systolic dysfunction

Highlights. The article presents a novel and unique method for assessment of left ventricular systolic disfunction using electrocardiography and photoplethysmography data. This method will improve and simplify the detection of cardiovascular diseases.Aim. To evaluate left ventricular (LV) systolic function using electrocardiogram (ECG) and photoplethysmogram (PPG) signals recorded by a single-channel ECG and PPG-based monitor.Methods. The prospective study included 489 patients over 18 years old with various cardiovascular diseases. All participants underwent echocardiography to determine the main indicators of LV systolic function: LV ejection fraction (EF), LV outflow tract velocity time integral (LVOT VTI), and global longitudinal strain (GLS). Moreover, all patients underwent 1-lead ECG and PPG recording using a single-channel ECG and PPG-based monitor (CardioQvark). The obtained data were analyzed, and ROC curve analysis was performed.Results. We have identified ECG and PPG parameters associated with a decrease in LV contractile function. During the analysis, the ECG, T-wave amplitude (TA) and RonsF parameters showed the highest diagnostic accuracy. With EF below 55%, the area under the ROC curve (AUC) was 0.822, sensitivity (Se) 80%, specificity (Sp) 69% in EF below 55% in TA; in RonsF AUC was 0.743, Se 81%, Sp 77%. With EF below 40%, AUC was 0.915, Se 85%, Sp 83% in TA, and in RonsF AUC was 0.844, Se 82%, Sp 82%. Diagnostic accuracy of ECG signals in case of LVOT VTI lower than 16 cm was measured: TA (AUC 0.755, Se 82%, Sp 70%), RonsF (AUC 0.620, Se 77%, Sp 72%). PPG signals were not significantly associated with reduced EF; however, the pulse wave parameters were associated with lower LVOT VTI: in DP-B0 AUC was 0.687, Se 71%, Sp 74%. The combination of ECG and PPG signals was significantly associated with EF below 40% (RonsF * DP-SEP (AUC 0.877, Se 86%, Sp 85%). ECG and PPG signals were not associated with LV GLS.Conclusion. Assessment of LV systolic function can be performed by analyzing ECG and PPG signals recorded using a portable single-channel CardioQvark monitor.</jats:p