Neurohormonal Dysregulation Research Articles

Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various phenotypes, and obesity is one of the most common and clinically relevant phenotypes of HFpEF. Obesity contributes to HFpEF through multiple mechanisms, including sodium retention, neurohormonal dysregulation, altered energy substrate metabolism, expansion of visceral adipose tissue, and low-grade systemic inflammation. Glucagon-like peptide-1 (GLP-1) is a hormone in the incretin family. It is produced by specialized cells called neuroendocrine L cells located in the distal ileum and colon. GLP-1 reduces blood glucose levels by promoting glucose-dependent insulin secretion from pancreatic β cells, suppressing glucagon release from pancreatic α cells, and blocking hepatic gluconeogenesis. Recent evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) can significantly improve physical activity limitations and exercise capacity in obese patients with HFpEF. The possible cardioprotective mechanisms of GLP-1 RAs include reducing epicardial fat tissue thickness, preventing activation of the renin-angiotensin-aldosterone system, improving myocardial energy metabolism, reducing systemic inflammation and cardiac oxidative stress, and delaying the progression of atherosclerosis. This review examines the impact of obesity on the underlying mechanisms of HFpEF, summarizes the trial data on cardiovascular outcomes of GLP-1 RAs in patients with type 2 diabetes mellitus, and highlights the potential cardioprotective mechanisms of GLP-1 RAs to give a pathophysiological and clinical rationale for using GLP-1 RAs in obese HFpEF patients.

Heart failure related fatigue: An exploratory analysis of serum osmolality from the national health and nutrition examination survey

BackgroundFatigue is a prominent symptom of heart failure (HF). However, underlying mechanisms remain poorly understood. Fluid volume status has been suggested as a physiologic mechanism of HF-related fatigue. Serum osmolality may fluctuate with changes in volume status associated with neurohormonal dysregulation. The relationship of fatigue to serum osmolality has not been assessed in adults with HF. ObjectivesDescribe the relationship between serum osmolality and fatigue in adults with HF. MethodsWe analyzed two waves of cross-sectional data from the National Health and Nutrition Examination Survey (2015–2016 and 2017–2018). Adults who self-reported having HF without select co-morbid conditions known to contribute to fatigue were included. Data were weighted to provide US national estimates, and complex sample design used for analyses. Sequential logistic regression was used to isolate the effect of serum osmolality on the odds of having fatigue. ResultsData from the sample represented 1.4 million Americans with HF (58.5 % male; median age 68 years), of whom 1,001,589 (67.9 %) reported fatigue. Participants with fatigue had lower serum osmolality compared to those without fatigue (t = -3.04, p = .009). Higher serum osmolality was associated with 8.8 % lower odds of experiencing fatigue when controlling for sex and body mass index (OR = 0.912, p = .007, CI 0.857 - 0.972). ConclusionsHF-related fatigue is associated with lower serum osmolality. Low serum osmolality may indicate excess volume and the presence of a heightened neurohormonal response, both of which may influence fatigue. Alternatively, serum osmolality may directly affect other physiologic changes that may contribute to fatigue.

Mitochondrial Dysfunction in Heart Failure: From Pathophysiological Mechanisms to Therapeutic Opportunities.

Mitochondrial dysfunction, a feature of heart failure, leads to a progressive decline in bioenergetic reserve capacity, consisting in a shift of energy production from mitochondrial fatty acid oxidation to glycolytic pathways. This adaptive process of cardiomyocytes does not represent an effective strategy to increase the energy supply and to restore the energy homeostasis in heart failure, thus contributing to a vicious circle and to disease progression. The increased oxidative stress causes cardiomyocyte apoptosis, dysregulation of calcium homeostasis, damage of proteins and lipids, leakage of mitochondrial DNA, and inflammatory responses, finally stimulating different signaling pathways which lead to cardiac remodeling and failure. Furthermore, the parallel neurohormonal dysregulation with angiotensin II, endothelin-1, and sympatho-adrenergic overactivation, which occurs in heart failure, stimulates ventricular cardiomyocyte hypertrophy and aggravates the cellular damage. In this review, we will discuss the pathophysiological mechanisms related to mitochondrial dysfunction, which are mainly dependent on increased oxidative stress and perturbation of the dynamics of membrane potential and are associated with heart failure development and progression. We will also provide an overview of the potential implication of mitochondria as an attractive therapeutic target in the management and recovery process in heart failure.

Role of Cognitive Frailty in Older Adults With Cardiovascular Disease.

As the older adult population expands, an increasing number of patients affected by geriatric syndromes are seen by cardiovascular clinicians. One such syndrome that has been associated with poor outcomes is cognitive frailty: the simultaneous presence of cognitive impairment, without evidence of dementia, and physical frailty, which results in decreased cognitive reserve. Driven by common pathophysiologic underpinnings (eg, inflammation and neurohormonal dysregulation), cardiovascular disease, cognitive impairment, and frailty also share the following risk factors: hypertension, diabetes, obesity, sedentary behavior, and tobacco use. Cardiovascular disease has been associated with the onset and progression of cognitive frailty, which may be reversible in early stages, making it essential for clinicians to diagnose the condition in a timely manner and prescribe appropriate interventions. Additional research is required to elucidate the mechanisms underlying the development of cognitive frailty, establish preventive and therapeutic strategies to address the needs of older patients with cardiovascular disease at risk for cognitive frailty, and ultimately facilitate targeted intervention studies.

The Role of Gut Microbiota and the Potential Effects of Probiotics in Heart Failure.

Heart failure (HF) remains a significant global health challenge, affecting millions of individuals worldwide and posing a substantial burden on healthcare systems. HF is a syndrome of intricate pathophysiology, involving systemic inflammation, oxidative stress, metabolic perturbations, and maladaptive structural changes in the heart. It is influenced by complex interactions between cardiac function, systemic physiology, and environmental factors. Among these factors, the gut microbiota has emerged as a novel and intriguing player in the landscape of HF pathophysiology. The gut microbiota, beyond its role in digestion and nutrient absorption, impacts immune responses, metabolic processes, and, as suggested by evidence in the literature, the development and progression of HF. There is a bidirectional communication between the gut and the heart, often known as the gut-heart axis, through which gut microbiota-derived metabolites, immune signals, and microbial products exert profound effects on cardiovascular health. This review aims to provide a comprehensive overview of the intricate relationship between the gut microbiota and HF. Additionally, we explore the potential of using probiotics as a therapeutic strategy to modulate the gut microbiota's composition and attenuate the adverse effects observed in HF. Conventional therapeutic approaches targeting hemodynamic and neurohormonal dysregulation have substantially improved the management of HF, but emerging research is exploring the potential implications of harnessing the gut microbiota for innovative approaches in HF treatment.

Pulmonary Hypertension and Right Ventricle: A Pathophysiological Insight.

Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by elevated pulmonary vascular pressure. Long-term PH, irrespective of its etiology, leads to increased right ventricular (RV) pressure, RV hypertrophy, and ultimately, RV failure. Research indicates that RV failure secondary to hypertrophy remains the primary cause of mortality in pulmonary arterial hypertension (PAH). However, the impact of PH on RV structure and function under increased overload remains incompletely understood. Several mechanisms have been proposed, including extracellular remodeling, RV hypertrophy, metabolic disturbances, inflammation, apoptosis, autophagy, endothelial-to-mesenchymal transition, neurohormonal dysregulation, capillary rarefaction, and ischemia. Studies have demonstrated the significant role of oxidative stress in the development of RV failure. Understanding the interplay among these mechanisms is crucial for the prevention and management of RV failure in patients with PH.

Cardiomyopathy in chronic kidney disease: clinical features, biomarkers and the contribution of murine models in understanding pathophysiology.

The cardiorenal syndrome (CRS) is described as a multi-organ disease encompassing bidirectionally heart and kidney. In CRS type 4, chronic kidney disease (CKD) leads to cardiac injury. Different pathological mechanisms have been identified to contribute to the establishment of CKD-induced cardiomyopathy, including a neurohormonal dysregulation, disturbances in the mineral metabolism and an accumulation of uremic toxins, playing an important role in the development of inflammation and oxidative stress. Combined, this leads to cardiac dysfunction and cardiac pathophysiological and morphological changes, like left ventricular hypertrophy, myocardial fibrosis and cardiac electrical changes. Given that around 80% of dialysis patients suffer from uremic cardiomyopathy, the study of cardiac outcomes in CKD is clinically highly relevant. The present review summarizes clinical features and biomarkers of CKD-induced cardiomyopathy and discusses underlying pathophysiological mechanisms recently uncovered in the literature. It discloses how animal models have contributed to the understanding of pathological kidney-heart crosstalk, but also provides insights into the variability in observed effects of CKD on the heart in different CKD mouse models, covering both "single hit" as well as "multifactorial hit" models. Overall, this review aims to support research progress in the field of CKD-induced cardiomyopathy.

24-year-old obese woman with dilated cardiomyopathy: a case report of obese cardiomyopathy

Background: Dilated cardiomyopathy is a disease characterized by enlargement of the heart ventricles with impaired left ventricular or biventricular systolic function. Obesity is a risk factor for changes in the structure and function of the heart, known as obese cardiomyopathy. The purpose of writing this case report is to holistically discuss obesity as a risk factor for dilated cardiomyopathy based on a literature review. Case presentation: A 24-year-old woman complained of shortness of breath 2 months ago, appeared during activities and while she slept at night, and improved when sitting and resting. Other complaints are palpitations, swollen feet, nausea, and vomiting. Childhood history of obesity. Blood pressure 160/95 mmHg, respiratory rate 22 times/minute, and body mass index 33.8 kg/m2 (obesity II). The jugular venous pressure is increased. Auscultation revealed a systolic murmur at ICS 4 grade 3/6 and pulmonary crackles, with pitting edema in the legs. Electrocardiography revealed sinus tachycardia. Laboratory tests showed high triglycerides and total cholesterol, and other laboratories were within normal limits. Echocardiographic examination showed decreased left ventricular systolic function, severe left ventricular dilatation, and an ejection fraction of 27.9%. No significant lesions were found during the angiographic examination. A magnetic resonance imaging examination revealed non-ischemic cardiomyopathy, moderate left ventricular dysfunction, and severe right ventricular dysfunction. Patients were given heart failure therapy according to guidelines. On routine control, the patient's condition was stable. Conclusion: Obesity is believed to be a risk factor for dilated cardiomyopathy through an increased hemodynamic load, neurohormonal dysregulation, inflammation, and lipotoxicity. Modalities such as the electrocardiogram, echocardiography, and magnetic resonance imaging can support the results of examinations for diagnosing dilated cardiomyopathy due to obesity. The management of obese cardiomyopathy involves changing lifestyles and administering drugs according to the clinical manifestations of heart failure.

Natriuretic Peptides: It Is Time for Guided Therapeutic Strategies Based on Their Molecular Mechanisms.

Natriuretic peptides (NPs) are the principal expression products of the endocrine function of the heart. They exert several beneficial effects, mostly mediated through guanylate cyclase-A coupled receptors, including natriuresis, diuresis, vasorelaxation, blood volume and blood pressure reduction, and regulation of electrolyte homeostasis. As a result of their biological functions, NPs counterbalance neurohormonal dysregulation in heart failure and other cardiovascular diseases. NPs have been also validated as diagnostic and prognostic biomarkers in cardiovascular diseases such as atrial fibrillation, coronary artery disease, and valvular heart disease, as well as in the presence of left ventricular hypertrophy and severe cardiac remodeling. Serial measurements of their levels may be used to contribute to more accurate risk stratification by identifying patients who are more likely to experience death from cardiovascular causes, heart failure, and cardiac hospitalizations and to guide tailored pharmacological and non-pharmacological strategies with the aim to improve clinical outcomes. On these premises, multiple therapeutic strategies based on the biological properties of NPs have been attempted to develop new targeted cardiovascular therapies. Apart from the introduction of the class of angiotensin receptor/neprilysin inhibitors to the current management of heart failure, novel promising molecules including M-atrial natriuretic peptide (a novel atrial NP-based compound) have been tested for the treatment of human hypertension with promising results. Moreover, different therapeutic strategies based on the molecular mechanisms involved in NP regulation and function are under development for the management of heart failure, hypertension, and other cardiovascular conditions.

The Africans in America study demonstrates that subclinical cardiovascular risk differs by etiology of abnormal glucose tolerance

Abnormal-glucose tolerance (Abnl-GT) is due to an imbalance between β-cell function and insulin resistance (IR) and is a major risk factor in cardiovascular disease (CVD). In sub-Saharan Africa, β-cell failure is emerging as an important cause of Abnl-GT (Abnl-GT-β-cell-failure). Visceral adipose tissue (VAT) volume and hyperlipidemia are major contributors to CVD risk when Abnl-GT is due to IR (Abnl-GT-IR). Yet, the CVD profile associated with Abnl-GT-β-cell failure is unknown. Therefore, our goals in 450 African-born Blacks (Male: 65%; Age: 39 ± 10 years; BMI 28 ± 5 kg/m2), living in America were to: (1) determine Abnl-GT prevalence and etiology; (2) assess by Abnl-GT etiology, associations between four understudied subclinical CVD risk factors in Africans: (a) subclinical myocardial damage (high-sensitivity troponin T (hs-cTnT)); (b) neurohormonal regulation (N-terminal pro-Brain-natriuretic peptide (NT-proBNP)); (c) coagulability (fibrinogen); (d) inflammation (high-sensitivity C-reactive protein (hsCRP)), as well as HbA1c, Cholesterol/HDL ratio and VAT. Glucose tolerance status was determined by the OGTT. IR was defined by the threshold at the lowest quartile for the Matsuda Index (≤ 2.97). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell-failure was defined as Abnl-GT without IR. VAT was assessed by CT-scan. For both the Abnl-GT-β-cell-failure and Abnl-GT-IR groups, four multiple regression models were performed for hs-cTnT; NT-proBNP; fibrinogen and hsCRP, as dependent variables, with the remaining three biomarkers and HbA1c, Cholesterol/HDL and VAT as independent variables. Abnl-GT occurred in 38% (170/450). In the Abnl-GT group, β-cell failure occurred in 58% (98/170) and IR in 42% (72/170). VAT and Cholesterol/HDL were significantly lower in Abnl-GT-β-cell-failure group vs the Abnl-GT-IR group (both P < 0.001). In the Abnl-GT-β-cell-failure group: significant associations existed between hscTnT, fibrinogen, hs-CRP, and HbA1c (all P < 0.05), and none with Cholesterol/HDL or VAT. In Abnl-GT-IR: hs-cTnT, fibrinogen and hsCRP significantly associated with Cholesterol/HDL (all P < 0.05) and NT-proBNP inversely related to fibrinogen, hsCRP, HbA1c, Cholesterol/HDL, and VAT (all P < 0.05). The subclinical CVD risk profile differed between Abnl-GT-β-cell failure and Abnl-GT-IR. In Abnl-GT-β-cell failure subclinical CVD risk involved subclinical-myocardial damage, hypercoagulability and increased inflammation, but not hyperlipidemia or visceral adiposity. For Abnl-GT-IR, subclinical CVD risk related to subclinical myocardial damage, neurohormonal dysregulation, inflammation associated with hyperlipidemia and visceral adiposity.ClinicalTrials.gov Identifier: NCT00001853.

Sleep disturbances in the context of neurohormonal dysregulation in patients with bipolar disorder

BackgroundSleep dysfunction is a core symptom in bipolar disorder (BD), especially during major mood episodes. This study investigated the possible link between subjective and objective sleep disturbances in inter-episode BD, changes in melatonin and cortisol levels, and circadian melatonin alignment. The study included 21 euthymic BD patients and 24 healthy controls. Participants had to wear an actigraphy device, keep a weekly sleep diary and take salivary samples: five samples on the last evening to determine the dim light melatonin onset (DLMO) and one the following morning to measure rising cortisol. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and Regensburg Insomnia Scale (RIS), and circadian alignment by the phase angle difference (PAD).ResultsIn comparison to healthy controls, BD patients had: (1) higher PSQI (5.52 ± 3.14 vs. 3.63 ± 2.18; p = 0.022) (significant after controlling for age and gender), and higher RIS scores (8.91 ± 5.43 vs. 5.83 ± 3.76; p = 0.031); (2) subjective a longer mean TST (p = 0.024) and TIB (p = 0.002) (both significant after controlling for age and gender), longer WASO (p = 0.019), and worse SE (p = 0.036) (significant after controlling for gender); (3) actigraphically validated earlier sleep onset (p = 0.002), less variation in sleep onset time (p = 0.005) and no longer TST (p = 0.176); (4) no differing melatonin levels (4.06 ± 2.77 vs. 3.35 ± 2.23 p = 0.352), an 1.65 h earlier DLMO (20.17 ± 1.63 vs. 21.82 ± 1.50; p = 0. 001) (significant after controlling for gender), and a phase advance of melatonin (6.35 ± 1.40 vs. 7.48 ± 1.53; p = 0.017) (significant after controlling for gender); and (5) no differing cortisol awakening response (16.97 ± 10.22 vs 17.06 ± 5.37 p = 0.969).ConclusionsPatients with BD, even in euthymic phase, have a significantly worse perception of their sleep. Advanced sleep phases in BD might be worth further investigation and could help to explain the therapeutic effects of mood stabilizers such as lithium and valproate.

Neurohumoral dysregulation in vibration disease (response features of hormonal complexes to the introduction of tyroliberin)

Introduction. The leading role in the body's adaptation to the external environment is the neuroendocrine system, although homeostatic mechanisms are highly diverse and at very different levels. Special functional hormonal tests can detect such disorders since obvious clinical manifestations do not accompany many neuroendocrine diseases. The use of tyroliberin with simultaneous determination of hormones of the peripheral endocrine gland and the corresponding tropic hormone of the pituitary gland in one portion of blood makes it possible to detect excessive or reduced hormonal secretion and diagnose the level of damage to the neuroendocrine system: hypothalamic, pituitary, peripheral. It seems relevant to characterize the features of the response of the pituitary-thyroid complex to the introduction of synthetic hypothalamic tyroliberin in vibration disease (VD). The study aims to develop objective criteria for detecting neurohormonal deregulation with varying degrees of severity of clinical manifestations of VD, to establish the pathogenetic, diagnostic, and prognostic significance of the detected changes. Materials and methods. Researchers examined three groups of patients: the first - persons with separate, early signs of vibration exposure (17 patients), the second - persons with grade 1 VD (26), the third - persons with grade 2 VD (27). The control group consisted of 37 practically healthy men, of similar age and profession, with no signs of vibration exposure. Results. In patients with VD, there is a qualitative and quantitative transition of the regulation of the pituitary-thyroid system, characterized by a different than average amount of thyroid hormones per unit of thyrotropin (TTH): less triiodothyronine (T3) and more thyroxine (T4). Since the primary source of T3 in the body is its conversion from T4 on the periphery in tissues, there is reason to believe that with the progression of clinical manifestations of vibration pathology, there is a decrease in the activity of this process. An increase in the T4/T3 ratios in parallel with the severity of the disease confirms this position. Conclusion. The features of the response of hormonal complexes to the introduction of synthetic hypothalamic tyroliberin were found, which made it possible to clarify the significance and role of neurohormonal dysregulation in the pathogenesis, diagnosis, and prediction of the risk of the occurrence and development of clinical manifestations of VD.

C-Reactive Protein and Frailty in Heart Failure

Frailty commonly coexists with heart failure and although both have been associated with neurohormonal dysregulation, inflammation, catabolism, and skeletal muscle dysfunction, there are still no defined biomarkers to assess frailty, especially from the perspective of populations with cardiovascular diseases. This is a cross-sectional study with 106 outpatients with heart failure, aged ≥60years, which aimed to assess frailty through a physical (frailty phenotype) and multidimensional (Tilburg Frailty Indicator) approach and to analyze its association with inflammatory and humoral biomarkers (high sensitivity C-reactive protein [hs-CRP], interleukin 6, tumor necrosis factor-α, insulin-like growth factor-1, and total testosterone), clinical characteristics, and functional capacity. In univariate analysis, hs-CRP was associated with frailty in both phenotype and Tilburg Frailty Indicator assessment (PR=1.005, 95% confidence interval [CI] 1.001 to 1.009, p=0.027 and PR=1.015, 95% CI 1.006 to 1.024, p=0.001, respectively), which remained significant in the final multivariate model in the frailty assessment by the phenotype (PR=1.004, 95% CI 1.001 to 1.008, p=0.025). There was no statistically significant difference between the groups for other biomarkers analyzed. Frailty was also associated with worse functional capacity, nonoptimized pharmacological treatment and a greater number of drugs in use, age, female gender, and a greater number of comorbidities. In conclusion, frailty is associated with higher levels of hs-CRP, which can indicate it is a promising frailty biomarker.

Goal-directed Therapy and Postcystectomy Ileus: Comment.

We read the article by Arslan-Carlon et al.1 with great interest. The authors are to be congratulated for their research on the impact of fluid therapy on postoperative ileus. In this recent randomized, controlled trial including 283 patients, they found no difference in the incidence of postoperative ileus between patients treated with a goal-directed therapy compared with a standard procedure in a homogenous open radical cystectomy patient cohort from a high caseload center.The pathogenesis of postoperative ileus is clearly multifactorial (fluid overload, opioids, neurohormonal dysregulation, gastrointestinal stretch, inflammatory response).2,3 In the era of enhanced recovery protocols including multiple preoperative, intraoperative, and postoperative optimization steps, it is not surprising to find that intraoperative goal-directed therapy alone has no impact on the return of bowel function compared with a moderate liberal fluid standard fluid administration. Furthermore, it remains questionable whether postoperative fluid substitution should be uniformly managed in patients who received either an intraoperative goal-directed therapy or a restrictive or relatively liberal fluid administration. Indeed, in this study net fluid during the hospitalization was higher in the standard group (−1,986 ml vs. −1,296 ml) but resulted in similar maximum body weight changes (2.7 kg vs. 3.0 kg) and could be interpreted as the consequence of a more aggressive diuretic therapy in the standard group postoperatively. This is of importance because postoperative submucosal edema has been postulated as a risk factor for a delayed return of gastrointestinal function.3 Unfortunately, the authors did not give any information on the postoperative administration of diuretics.The problem of adequate terminology is another ongoing issue. We were surprised by the authors’ comment in the discussion that the term constipation was not adequately described in the article by Wuethrich et al., as both the term constipation as well as the term ileus were defined in the appendix. Constipation was defined as no passage of stool without signs of ileus by postoperative day 5 and could be considered similar to what was considered a primary postoperative ileus in the article by Arslan-Carlon et al. This definition was based on the nomenclature resulting from a well-performed case series analysis aiming to standardize complications after cystectomy from the Department of Urology at the Sloan-Kettering Cancer Center (New York, New York).5 Perhaps the authors could specify why they did not apply their own above-mentioned definition in the present study. We recognize that the publication by Shabsigh et al. is more than 10 yr old, but the goal of a good standardized reporting methodology should be its continued long-term applicability. The Clavien Dindo classification remains the best example hereof.4,6 In the context of prevention of postoperative ileus, it would also be interesting to know which opioid antagonist was administered subcutaneously perioperatively.Finally, no data are presented about the systemic administration of opioids, a known risk factor for delayed return of bowel function. We only learn that patients received an epidural analgesia with a mixture containing a very low dose of bupivacaine (0.05%) and a relatively high dosage of opioid (8 μg/ml hydromorphone).In conclusion, the saying “one size does not fit all” can also be applied to fluid therapy. This study is of importance because it shows no benefit of goal-directed therapy in terms of reducing gastrointestinal-related complication rates. A more selective and differentiated approach in fluid management is needed. In some cases, restrictive fluid therapy may be beneficial, and in other cases, a modestly liberal fluid administration resulting in a postoperative weight gain of approximately 2 to 3 kg would make no difference in outcome. Fluid management is only part of a complex battery of interventions affecting outcome after open radical cystectomy.The authors declare no competing interests.

S0478 Gastroparesis Adversely Impacts Pregnancy Outcomes

INTRODUCTION: Gastroparesis is a chronic condition characterized by delayed gastric emptying in the absence of mechanical obstruction. Pregnancy is often complicated by nausea and vomiting, possibly related to the neurohormonal dysregulation. There is a paucity of literature addressing the impact of gastroparesis on pregnancy outcomes. Hence, we sought to study the effect of gastroparesis on maternal and fetal outcomes during pregnancy. METHODS: The National Readmission Database (NRD 2016–2017) was queried to capture all pregnancies using ICD-10 codes. Of this cohort, pregnancies complicated by gastroparesis were identified using ICD-10 code (K31.84), which was internally validated in our institution. Gastroparesis related outcomes (malnutrition, need for gastrostomy tube), and pregnancy-related outcomes (preeclampsia, miscarriages, preterm labor, etc.) were compared between pregnancies with and without gastroparesis. Propensity-score matched analysis using weighted regression models were used to compare the maternal and fetal outcomes between the two groups. RESULTS: Among 1990 women with gastroparesis, there were higher frequency of hyperemesis gravidarum, anemia, malnutrition, preeclampsia/eclampsia, and intrauterine fetal death compared to those without gastroparesis on univariate analysis. Propensity weighed analysis showed that gastroparesis in pregnancy is associated with pre-eclampsia (7.87% vs 4.85%, OR: 1.67; 95% CI: [1.29–2.17]), malnutrition (2.25% vs 0.63%, OR: 2.25; 95% CI: [1.21–4.18]), higher 30-day readmission (22.75% vs 10.71%, OR: 2.46; 95% CI: [2.00–3.02]) and longer hospital stay (5.18 vs 4.43 days, Coefficient: 0.75 ; 95% CI: [0.15–1.36]), compared to non-gastroparesis group (Table 1). CONCLUSION: Gastroparesis adversely impacts maternal outcome during pregnancy, often complicated by preeclampsia, hyperemesis gravidarum, malnutrition, and anemia. Targeted management of gastroparesis, including nutritional support, glycemic control, appropriate management of the symptoms and its complications would be of paramount importance in reducing the adverse outcomes during pregnancy.Table 1.: Analysis of outcomes in the propensity weighted sample

Regional adiposity and heart failure with preserved ejection fraction.

The role of obesity in the pathogenesis of heart failure (HF), and in particular HF with preserved ejection fraction (HFpEF), has drawn significant attention in recent years. The prevalence of both obesity and HFpEF has increased worldwide over the past decades and when present concomitantly suggests an obese-HFpEF phenotype. Anthropometrics, including body mass index, waist circumference, and waist-to-hip ratio, are associated with incident HFpEF. However, the cardiovascular effects of obesity may actually be driven by the distribution of fat, which can accumulate in the epicardial, visceral, and subcutaneous compartments. Regional fat can be quantified using non-invasive imaging techniques, including computed tomography, magnetic resonance imaging, and dual-energy X-ray absorptiometry. Regional variations in fat accumulation are associated with different HFpEF risk profiles, whereby higher epicardial and visceral fat have a much stronger association with HFpEF risk compared with elevated subcutaneous fat. Thus, regional adiposity may serve a pivotal role in the pathophysiology of HFpEF contributing to decreased cardiopulmonary fitness, impaired left ventricular compliance, upregulation of local and systemic inflammation, promotion of neurohormonal dysregulation, and increased intra-abdominal pressure and vascular congestion. Strategies to reduce total and regional adiposity have shown promise, including intensive exercise, dieting, and bariatric surgery programmes, but few studies have focused on HFpEF-related outcomes among obese. Further understanding the role these variable fat depots play in the progression of HFpEF and HFpEF-related hospitalizations may provide therapeutic targets in treating the obese-HFpEF phenotype.

A multi-perspective analysis of dissemination, etiology, clinical view and therapeutic approach for binge eating disorder (BED).

Eating disorders (ED) constitute the third most common group of chronic diseases among people aged 14-19 years after asthma and obesity, and one of their forms is binge eating disorder (BED). The purpose of the present review was to summarize new research findings on BED and overview the epidemiology, characteristics, criteria, etiopathogenesis, and treatment. Etiopathogenesis of BED is still poorly understood, and the current state of knowledge leads to the conclusion that the pathomechanism of the development and persistence of the symptoms of that disorder is very complicated - factors influencing these symptoms have a genetic, neurobiological, biochemical, cognitive, and emotional background. Treatment targeted at selected pathogenetic mechanisms - i.a., disturbance in the corticostriatal circuit, neurohormonal dysregulation or incorrect regulation of emotions - may be of help for people with binge eating disorder. Often comorbid mental, e.g., mood, anxiety and personality disorders, psychoactive substance abuse, suicidal ideation and suicide attempts, and somatic problems are particularly crucial in the context of primary care physicians and psychiatrists work and should encourage the expanding knowledge about BED and the creation of interdisciplinary therapeutic teams.

Dynamics of Psychological Status and Quality of Life Indicators in Patients with Diabetes Mellitus Type 2 and Chronic Gastritis Before and After the Treatment

Depression increases the risk of diabetes mellitus type 2 development and the subsequent risks of hyperglycemia, insulin resistance, micro- and macro-vascular complications. The association between depression and diabetes mellitus type 2 may include autonomic and neurohormonal dysregulation, weight gain, inflammation, and structural changes in the hippocampus.&#x0D; Objective of the work. To evaluate the psychological status and quality of life indicators in patients with diabetes mellitus type 2 and chronic gastritis before and after the treatment with the use of medicine Magnicum-Antistress.&#x0D; Materials and methods. Based on the Endocrinology Department of the Transcarpathia Regional Clinical hospital named after A.Novak there were examined 40 patients, whose average age was to 53.7±4.1 years. All patients with diabetes mellitus type 2 and chronic gastritis were assessed for quality of life, psychological status, and stress levels using questionnaires, namely using the SF-36, “PSM-25 Psychological Stress Scale methodology”, Holmes and Rahe stress test. After the survey, all patients were treated with Magnicum-Antistress medicine on the background of pathogenetic treatment.&#x0D; Results. Thus, after the course of treatment during 1 month, the level of stress decreased, so in the male patients the high level of stress was observed in 58.3% of patients, and among female patients – 35.8%. Also, the level of stress-resistance increased, so in male patients, the low stress-resistance level was observed in 66.7% of patients, and among female patients – 25%. After the course of treatment according to the Quality of Life Assessment Scale (SF-36), patients showed a positive tendency in the indicators of the psychological and physical health components.&#x0D; Conclusions. The level of chronic stress in patients with DM type 2 and CG is mostly high (52.5%). The level of stress-resistance in the vast majority of patients with DM type 2 and CG is low (52.5%). Complex therapy with the use of the medicine Magnicum-Antistress in patients with DM type 2 and CG is pathogenetically justified, and also leads to an improvement in the quality of life and stress-resistance in these patients.

Preclinical development of a miR-132 inhibitor for heart failure treatment

Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression. We previously demonstrated that miR-132 is both necessary and sufficient to drive the pathological cardiomyocytes growth, a hallmark of adverse cardiac remodelling. Therefore, miR-132 may serve as a target for HF therapy. Here we report further mechanistic insight of the mode of action and translational evidence for an optimized, synthetic locked nucleic acid antisense oligonucleotide inhibitor (antimiR-132). We reveal the compound’s therapeutic efficacy in various models, including a clinically highly relevant pig model of HF. We demonstrate favourable pharmacokinetics, safety, tolerability, dose-dependent PK/PD relationships and high clinical potential for the antimiR-132 treatment scheme.

Obstructive Sleep Apnea, Hypertension, and Cardiovascular Risk: Epidemiology, Pathophysiology, and Management.

Given the rising prevalence of obstructive sleep apnea (OSA), we aimed to review the epidemiologic and pathophysiologic relationship of OSA, hypertension, and cardiovascular disease, and to summarize recent advances in the treatment of OSA. OSA is associated with an elevated risk of hypertension and cardiovascular disease. Several pathophysiologic factors contribute to the relationship between OSA and vascular risk, including neurohormonal dysregulation, endothelial dysfunction, and inflammation. While CPAP reduces blood pressure, it has not been demonstrated to reduce cardiovascular risk. The combination of CPAP and weight loss has a synergistic effect on blood pressure and several metabolic parameters. Adherence to CPAP is poor across studies, potentially contributing to the attenuation of perceived cardiovascular benefit from CPAP therapy. A greater emphasis on adherence to CPAP and the combination of CPAP and weight loss are central to reducing cardiovascular risk among individuals with OSA.