Blood Pressure Response and Symptoms During Active Standing Test Among Hospitalized and Outpatients With Heart Failure: Results From the GRAVITY-HF Prospective Observational Cohort Study.

BACKGROUND: We conducted a multicenter, prospective, observational study to describe the incidence of orthostatic hypotension (OH) and orthostatic hypertension (OHtn) and its association with symptoms at standing and outcomes in patients with heart failure (HF). METHODS AND RESULTS: 321 active standing tests were performed in 87 inpatients during admission, and 316 tests were performed in 208 outpatients during follow-up. Blood pressure (BP) was measured by an automatic device 4 times in the supine position and at 1, 3 and 5 minutes of standing. Patients were queried about symptoms of orthostatic intolerance. The incidence of OH and OHtn was similar in both groups at baseline (classical OH 11%-22%, OHtn 3%-8%, depending on definition and timing). Reproducibility of BP changes with standing was low. Up to 50% of cases with abnormal responses were asymptomatic. Symptoms were variable and occurred mainly during the first minute of standing and had a U-shaped association with BP changes. OH in outpatients with HF was associated with a higher risks of death or readmission due to HF. CONCLUSIONS: Patients with HF have variable hemodynamic responses and symptoms during repeated active standing tests. OH might identify outpatients with HF who are at risk of long-term negative outcomes.

Progression of obstructive sleep apnoea after renal denervation is not associated with hypertension exaggeration.

PURPOSE: In a cohort, observational prospective trial, we assessed the long-term dynamics of sleep-disordered breathing in patients with resistant hypertension after renal denervation and their association with blood pressure change at remote follow-up. MATERIALS AND METHODS: Twenty-eight patients with stable hypertension who were recruited for endovascular radiofrequency renal denervation in 2012-2019 and had valid both baseline and follow-up sleep study, were included in the analysis. All patients underwent physical examination, anthropometry, office and ambulatory blood pressure measurements, blood and urine tests, kidney visualization, and full polysomnography before and within 12-36 months after renal denervation. RESULTS: The average follow-up comprised 30.1 ± 8.4 months. At long-term follow-up, no significant changes in creatinine level, estimated glomerular filtration rate, body mass index were registered. There was a significant increase in sleep apnea severity indices: the mean change in apnea-hypopnea index comprised 9.0(-21.1;25.2) episodes/h, in oxygen desaturation index 6.5(-16.8;35.9) episodes/h, in the average SpO2 -1.7(-5.6;1.9)%. Over 12-month follow-up, there were no significant differences in blood pressure response in patients with and without sleep apnea. The baseline apnea-hypopnea and oxygen desaturation indices and the mean SpO2 were associated with the circadian blood pressure profile at follow-up, but did not correlate with the blood pressure response. CONCLUSIONS: Although the severity of sleep apnea worsens at > 12 months follow-up after renal denervation, this is not associated with hypertension exaggeration.

Value-based approach to blood pressure telemonitoring and remote counseling in hypertensive patients.

PURPOSE: Blood pressure telemonitoring and remote counselling (BPTM) improves blood pressure (BP) control in patients with hypertension (HTN). Studies assessing the efficacy of BPTM from a value-based perspective are lacking. We investigated whether BPTM fits all principles of the value-based approach (clinical and economic effectiveness, improvement in patient-reported outcome/experience measures (PROM/PREM)). MATERIALS AND METHODS: Two hundred and forty ambulatory patients with uncontrolled HTN were randomised in a 2: 1 manner to BPTM (n = 160, mean age 47 y.o.) and usual care (UC, n = 80; 49 y.o.) with baseline and 3-month follow-up clinic visits. BPTM employed a mobile application (for patients) and a desktop version (for clinician), which allowed communication and exchange of medical data. The main outcomes were changes in office and ambulatory systolic (S) BPs, rate of BP control. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were evaluated in economic analysis. The MOS SF-36 score was taken as a PROM, and the PEQ score was used as a PREM. RESULTS: Larger decreases in office and ambulatory SBPs (-16.8 and -8.9 mm Hg, respectively; p < .05) was achieved in BPTM group while the treatment intensity was equal (2.4 drugs). The ICER 11.1 EUR/-1 mm Hg 24-hour SBP/1 year was 75% effective as per willingness-to-pay threshold. BPTM improved PROM (+2.1 in mean MOS SF-36; p = .04), reduced long-term mortality (+0.11 life years gained), leading to +0.49 quality-adjusted life years (QALYs) gained as compared with UC. The ICUR was 4 169.4 EUR/QALY gained. Patient-reported experience was higher in the BPTM (+10 PEQ, p = .01). The UC group showed minor changes in MOS SF-36 and PEQ (+1.3; +6, respectively; p n.s.). CONCLUSIONS: Being cost-effective, BPTM incorporates both clinical benefits and patient-perceived value. Larger randomised studies are needed to confirm our findings.

Time Series Forecasting of Cardiovascular Mortality: Machine Learning Based on State Economic and Local Medical Data.

This study focuses on the complex interplay of healthcare, economic factors, and population dynamics, addressing a research gap in regional-level models that integrate diverse features within a temporal framework. Our primary objective is to develop an advanced temporal model for predicting cardiovascular mortality in Russian regions by integrating global and local healthcare features with economic and population dynamics. Utilizing a dataset from the Almazov Center's Department of Mortality Performance Monitoring, covering 94 regions and 752 records from January 1, 2015, to December 31, 2023, our analysis incorporates key parameters such as angioplasty procedures, population morbidity rates, Ischemic Heart Disease (IHD) and Cardiovascular Diseases (CVD) monitoring, and demographic data. Employing XGBoost and a regression model, our methodology ensures the model's robustness and generalizability.

Russian-language translation and cultural adaptation of the Norwegian 'Patient Experience Questionnaire'.

The availability of patient-reported experience measures (PREM) is an unmet need in Russian healthcare. Objective: To translate, adapt culturally, and validate PREM for outpatients. Methods: A core set of questions from the Patient Experience Questionnaire (PEQ, in Norwegian, available in English) was translated to Russian (forward-backward translation). Acceptability, construct validity, and reliability were assessed. Patients aged ≥18 y.o. were invited to complete the questionnaire via QR-code within 24 h after a medical encounter. Results: A questionnaire with adequate conceptual and linguistic equivalence was obtained. For four questions, a rating scale was replaced by Likert-type. A total of 308 responses were received (median age 55 y.o., 52% females). The correlation matrix was factorable. Four factors were extracted using varimax rotation: 1) outcome of this specific visit; 2) communication experiences; 3) communication competency; 4) emotions after this visit. These explained 65.4% of the total variance. Three items were excluded. The model was confirmed to be adequate. The Cronbach alpha was >0.9. Item-total correlation confirmed discriminative validity. Conclusion: These preliminary results show that the Russian version of PEQ, adapted to national features, shows good psychometric properties. External validation is needed for the broad implementation of this PREM. Innovation: This research is first attempt to use PREM in the Russian Federation. The use of quick response codes is feasible and eases survey conduction. The more PREMs are used the higher the quality of healthcare.

Prognosis and cardiovascular morbidity and mortality in prospective study of hypertensive patients with obstructive sleep apnea syndrome in St Petersburg, Russia.

BACKGROUND: To assess the impact of obstructive sleep apnea-hypopnea syndrome (OSAHS) on prognosis and cardiovascular morbidity and mortality in relation to other major cardiovascular risk factors. MATERIAL/METHODS: This prospective study recruited 234 patients from an out-patient clinic. Based on the Berlin questionnaire, 147 patients (90 males, mean age 52.1 ± 10.4 years) with highly suspected sleep breathing disorders were included in the study. Based on cardiorespiratory monitoring, patients were divided into 2 groups: 42 patients without sleep breathing disorders (SBD), and 105 patients with OSAHS. Among these, 12 patients started CPAP therapy and formed the third group. RESULTS: The mean follow-up period was 46.4 ± 14.3 months. Event-free survival was lowest in the untreated OSAHS patients (log rank test 6.732, p = 0.035). In the non-adjusted regression model, OSAHS was also associated with a higher risk of cardiovascular events (OR = 8.557, 95% CI 1.142-64.131, p = 0.037). OSAHS patients demonstrated higher rates of hospitalization compared to the control group without SBD (OR 2.750, 95%CI 1.100-6.873, p = 0.04). CONCLUSIONS: OSAHS hypertensive patients, and in particular, according to our model, patients with severe OSAHS (AHI ≥ 30/h), are at higher risk of fatal and non-fatal cardiovascular events. Moreover, untreated OSAHS patients demonstrate higher rates of hospitalization caused by the onset or deterioration of cardiovascular disease.

Survival Analysis of COVID-19 Patients in Russia Using Machine Learning.

The current pandemic can likely have several waves and will require a major effort to save lives and provide optimal treatment. The efficient clinical resource planning and efficient treatment require identification of risk groups and specific clinical features of the patients. In this study we develop analyze mortality for COVID19 patients in Russia. We identify comorbidities and risk factors for different groups of patients including cardiovascular diseases and therapy. In the study we used a Russian national COVID registry, that provides sophisticated information about all the COVID-19 patients in Russia. To analyze Features importance for the mortality we have calculated Shapley values for the "mortality" class and ANN hidden layer coefficients for patient lifetime. We calculated the distribution of days spent in hospital before death to show how many days a patient occupies a bed depending on the age and the severity of the disease to allow optimal resource planning and enable age-based risk assessment. Predictors of the days spent in hospital were calculated using Pearson correlation coefficient. Decisions trees were developed to classify the patients into the groups and reveal the lethality factors.

Modelling of COVID-19 Morbidity in Russia.

The outbreak of COVID-19 has led to a crucial change in ordinary healthcare approaches. In comparison with emergencies re-allocation of resources for a long period of time is required and the peak utilization of the resources is also hard to predict. Furthermore, the epidemic models do not provide reliable information of the development of the pandemic's development, so it creates a high load on the healthcare systems with unforeseen duration. To predict morbidity of the novel COVID-19, we used records covering the time period from 01-03-2020 to 25-05-2020 and include sophisticated information of the morbidity in Russia. Total of 45238 patients were analyzed. The predictive model was developed as a combination of Holt and Holt-Winter models with Gradient boosting Regression. As we can see from the table 2, the models demonstrated a very good performance on the test data set. The forecast is quite reliable, however, due to the many uncertainties, only a real-world data can prove the correctness of the forecast.

Identification of Diabetes Risk Factors in Chronic Cardiovascular Patients.

Specific predictive models for diabetes polyneuropathy based on screening methods, for example Nerve conduction studies (NCS, can reach up to AUC 65.8 - 84.7 % for the conditional diagnosis of DPN in primary care. Prediction methods that utilize data from personal health records deal with large non-specific datasets with different prediction methods. Li et al. utilized 30 independent variables, which allowed to implement a model with AUC = 0.8863 for a Multilayer perceptron (MLP). Linear regression (LR) based methods produced up to AUC = 0.8 %. This way, modern data mining and computational methods can be effectively adopted in clinical medicine to derive models that use patient-specific information to predict the development of diabetic polyneuropathy, however, there still is a space to improve the efficiency of the predictive models. The goal of this study is the implementation of machine learning methods for early risk identification of diabetes polyneuropathy based on structured electronic medical records. It was demonstrated that the machine learning methods allow to achieve up to 0.7982 precision, 0.8152 recall, 0.8064 f1-score, 0.8261 accuracy, and 0.8988 AUC using the neural network classifier.

Addressing Orthostatic Hypotension in Heart Failure: Pathophysiology, Clinical Implications and Perspectives.

Heart failure (HF)is a condition at high risk for orthostatic hypotension (OH)given the large proportion of patients at an advanced age and high burden of comorbidities contributing to OH, as well as a high prevalence of medications with neurovascular and volume modulating properties. Early identification of OH in HF seems to be crucial as OH can have an impact on patient symptoms, activity level and independence, be a marker of specific pathophysiological changes or be an indicator of need for personalized treatment. OH might contribute significantly to bad enough prognosis in HF, as, besides a risk of falls and cognitive decline, it was found to be associated with cardiovascular morbidity and mortality. In this review, we aimed to incentivize the routine use of orthostatic testing in HF, as well as stimulate future research in this field, which could lead to significant advances in the treatment and outcomes.

The role of selective imidazoline receptor agonists in modern hypertension management: an international real-world survey (STRAIGHT).

BACKGROUND: Multiple pharmacologic strategies are currently available to lower blood pressure (BP). Renin-angiotensin system (RAS)-inhibitors, calcium channel blockers and diuretics are widely recommended as first line therapies. Sympathetic activation is an important contributor to BP elevation but remains unopposed or is even increased by some of these drug classes. Selective imidazoline receptor agonists (SIRAs) reduce increased central sympathetic outflow and are considered as add-on therapy in most guidelines. We conducted an international survey to evaluate contemporary hypertension management strategies in countries with high prescription rates of SIRAs to better understand the rationale and practical indications for their use in a real-world setting. METHODS: Physicians from seven countries (India, Jordan, Lebanon, Russia, Saudi Arabia, South Africa, United Arab Emirates) were asked to complete a web-based questionnaire and comment on clinical case scenarios to provide information on their current practice regarding antihypertension strategies, underlying rationale for their choices, and adherence to relevant guidelines. RESULTS: 281 physicians completed the questionnaire including mainly cardiologists (35%) and general practitioners (32%). 96% reported using European (60%) or local (56%) guidelines in their daily practices. The majority of responding physicians (83%) had knowledge of SIRAs and 70% prescribed SIRAs regularly typically as a third line antihypertensive strategy (63%). The preferred combination partners for SIRAs were RAS-inhibitors (72%). CONCLUSIONS: Contemporary hypertension management varies between countries and therapeutic approaches in a real-world setting are not always in line with recommendations from available guidelines. In the countries selected for this survey prescription of SIRAs was common and appeared to be guided predominantly by considerations relating to the underlying pathophysiologic mechanism of sympathetic inhibition.

The use of single-pill combinations as first-line treatment for hypertension: translating guidelines into clinical practice.

: The 2008 European Society of Cardiology/European Society of Hypertension guidelines recommend the first-line prescription of two antihypertensive drugs in single-pill combinations (SPCs), also known as fixed-dose combinations, for the treatment of most patients with hypertension. This recommendation is based on a large amount of data, which shows that first-line treatment with SPCs supports reaching blood pressure targets rapidly and reducing cardiovascular outcome risk while keeping the therapeutic strategies as simple as possible and fostering adherence and persistence. As this approach constitutes a big shift from the stepped-care approaches that have been dominant for many years, practicing physicians have expressed concerns about using SPCs as first-line agents. In this review, we will discuss the barriers to the uptake of this recommendation. We will also offer suggestions to reduce the impact of these barriers and address specific concerns that have been raised.

Predictors of heart rhythm disturbances in hypertensive obese patients with obstructive sleep apnea.

OBJECTIVE: To assess the incidence and predictors of heart rhythm and conduction disturbances in hypertensive obese patients with and without obstructive sleep apnea (OSA). METHODS: This is an open, cohort, prospective study. Out of 493 screened patients, we selected 279 hypertensive, obese individuals without severe concomitant diseases: 75 patients without sleep-disordered breathing (non-SDB group), and 204 patients with OSA (OSA group). At baseline, all patients underwent examination, including ECG, Holter ECG monitoring, and sleep study. During follow-up (on 3, 5, 7 and 10th years; phone calls once per 6 months), information about new events, changes in therapy and life style was collected, diagnostic procedures were performed. As the endpoints, we registered significant heart rhythm and conduction disorders as following: atrial fibrillation (AF), ventricular tachycardia, atrioventricular block (AV) 2-3 degree, sinoatrial block, significant sinus pauses (> 2000 ms), and the required pacemaker implantation. RESULTS: The median follow-up was 108 (67.5-120) months. The frequency of heart rhythm disorders was higher in OSA patients (29 cases, χ2 = 5.5; Р = 0.019) compared to the non-SDB patients (three cases; OR: 3.92, 95% CI: 1.16-13.29). AF was registered in 15 patients (n = 12 in OSA group; Р = 0.77). Heart conduction disturbance developed in 16 patients, without an association with the rate of coronary artery disease onset. Regression analysis showed that only hypertension duration was an independent predictor of AF (OR: 1.10, 95% CI: 1.04-1.16; Р = 0.001). In case of heart conduction disturbances, apnea duration was the strongest predictor (Р = 0.002). CONCLUSIONS: Hypertensive obese patients with OSA demonstrate 4-fold higher incidence of heart rhythm and conduction disturbances than subjects without SDB. Hypertension duration is an independent predictor for AF development, while sleep apnea/hypopnea duration is the main factor for heart conduction disorders onset in hypertensive obese patients with OSA.

Zinc inhibits nuclear factor-kappa B activation and sensitizes prostate cancer cells to cytotoxic agents.

Prostate carcinogenesis involves transformation of zinc-accumulating normal epithelial cells to malignant cells, which do not accumulate zinc. In this study, we demonstrate by immunoblotting and immunohistochemistry that physiological levels of zinc inhibit activation of nuclear factor (NF)-kappa B transcription factor in PC-3 and DU-145 human prostate cancer cells, reduce expression of NF-kappa B-controlled antiapoptotic protein c-IAP2, and activate c-Jun NH(2)-terminal kinases. Preincubation of PC-3 cells with physiological concentrations of zinc sensitized tumor cells to tumor necrosis factor (TNF)-alpha, and paclitaxel mediated cell death as defined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. These results suggest one possible mechanism for the inhibitory effect of zinc on the development and progression of prostate malignancy and might have important consequences for the prevention and treatment of prostate cancer.

Is Mixed Apnea Associated with Non-Rapid Eye Movement Sleep a Reversible Compensatory Sign of Heart Failure?

BACKGROUND: Sleep-disordered breathing is common in heart failure (HF), and prolonged circulation time and diminished pulmonary volume are considered the main possible causes of sleep apnea in these patients. However, the impact and interrelation between sleep apnea and HF development are unclear. We report the case of a patient with complete elimination of non-rapid-eye-movement (NREM) sleep-associated mixed apnea in HF after heart transplantation. CASE REPORT: After unsuccessful 12-month conventional treatment with abrupt exacerbation of biventricular HF IV class (according to New York Heart Association Functional Classification), a 26-year-old man was admitted to the hospital. Based on a comprehensive examination including endomyocardial biopsy, dilated cardiomyopathy was diagnosed. Heart transplantation was considered the only possible treatment strategy. Polysomnography showed severe NREM sleep-associated mixed sleep apnea [apnea-hypopnea index 43/h, in rapid eye movement (REM) sleep 3.7/h, in NREM sleep 56.4/h, mean SatO2 93.9%], and periodic breathing. One-month post-transplantation polysomnography did not show sleep-disordered breathing (apnea-hypopnea index 1.0/h; in REM sleep - 2.8/h, in NREM sleep 0.5/h, mean SatO2 97.5%). The patient was discharged from the hospital in improved condition. CONCLUSIONS: NREM sleep-associated mixed apnea occurring in severe systolic HF due to dilated cardiomyopathy might be reversible in case of successful HF treatment. We suggest that mixed sleep apnea strongly associated with NREM sleep occurs in HF, when the brain centers regulating ventilation are intact, and successful HF compensation might be highly effective regarding sleep-breathing disorders without non-invasive ventilation. This is important to know, especially with regard to the recently published data of potentially unfavorable effects of adaptive servoventilation in systolic HF, and the lack of other treatment options.

New insights into the management of rhythm and conduction disorders after acute myocardial infarction.

PATIENT: Male, 53 FINAL DIAGNOSIS: Myocardial infarction Symptoms: Chest pain • tachycardia MEDICATION: - Clinical Procedure: - Specialty: Cardiology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: Comorbidities, including obesity and sleep-breathing disorders, can adversely influence outcomes in acute myocardial infarction (AMI), and should be considered in diagnosis and treatment administration. CASE REPORT: The case demonstrates the difficulties of treating a middle-aged Caucasian patient with multiple comorbidities that could be overcome by a personalized approach and evaluation of concomitant sleep-breathing disorders (by polysomnography study). Diagnosis and treatment of sleep apnea by positive airway pressure (PAP therapy) played a pivotal role in heart rate and rhythm control. CONCLUSIONS: In this case, effective PAP therapy enabled titration of antiarrhythmic drugs (to maximal doses) to achieve heart rate control and to eliminate severe ventricular tachyarrhythmias and contributed to the better recovery in a post-AMI patient with left ventricular systolic dysfunction.