Heart Failure Disorders Research Articles

P164 SOLUBLE GUANYLATE CYCLASE STIMULATORS: AN EMERGING OPTION IN THE TREATMENT OF PRESSURE AND VOLUME OVERLOAD INDUCED CHRONIC HEART FAILURE

Pressure and volume overload-induced chronic heart failure (HF) is associated with characteristic cardiac remodeling and ventricular myocardial proteomic alterations, that can lead to the formation of a substrate for arrhythmias. Antiarrhythmic drug therapy is still suboptimal and current therapies are not efficacious enough. The purpose of the current study was therefore to examine the efficiency of nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) stimulator. We used as an experimental model male hypertensive Ren-2 transgenic rats (TGR) (n = 16), normotensive Hannover Sprague–Dawley rats (HSD, n = 17), and a volume-overload HF rat model induced by creating the aortocaval fistula (ACF) in rats of both strains (n = 27). Rats were after the induction of ACF treated by sGC stimulator BAY41-8543 (3 mg/kg/day for 30 weeks) alone or combined with angiotensin-converting enzyme inhibitor (ACEi) Trandolapril (0.25 mg/kg/day for 30 weeks). The age of the animals at the end of the experiment was 40 weeks. Left ventricle tissue and plasma samples were used for further analyses. Blood pressure (BP) was measured by telemetry. Combined treatment with sGC stimulator and ACEi was the most potent in lowering BP. Moreover, supplementation by sGC stimulator alone significantly decreased mortality and increased levels of the antioxidant enzyme superoxide dismutase 1, matrix metalloproteinase 2, total and phosphorylated connexin 43 as well as protein kinase C epsilon, implicated in remodeling of extracellular matrix and intercellular communication, in the left ventricle of TGR rats. Application of the sGC stimulator also slightly normalized elevated collagen deposition and hydroxyproline content in the left ventricular tissue of TGR rats. Unfortunately, we did not observe any effect of the sGC stimulator in the TGR ACF group. These results support the hypothesis that sGC stimulators might represent a class of drugs suitable for the prevention and treatment of related disorders in HF. This work was supported by APVV-21-0410, VEGA 2/0006/23, and EXCELES LX22NPO5104. Supported by APVV-21-0410, VEGA 2/0006/23, and EXCELES LX22NPO5104.

Autoimmune Disorders in Heart Failure With Preserved Ejection Fraction

BackgroundInflammation plays a fundamental role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of an underlying systemic inflammatory disease such as rheumatoid arthritis or systemic lupus erythematosus. ObjectivesThis study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and autoimmune or primary inflammatory disorders. MethodsOf 982 consecutively evaluated patients with HFpEF diagnosed, 79 (8.0%) had autoimmune disorders. HFpEF was defined by invasive cardiopulmonary hemodynamic exercise testing. ResultsFemale sex, higher heart rate, lower hemoglobin, absence of atrial fibrillation, and absence of coronary artery disease were independently associated with autoimmune disorders. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with autoimmune disorders, reflected by lower arterial-venous oxygen content difference at rest (4.2 ± 0.7 mL/dL vs 4.6 ± 1.0 mL/dL; P < 0.001) and during exercise (9.3 ± 2.2 mL/dL vs 10.4 ± 2.2 mL/dL; P < 0.001), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCo2 slope, regression slope relating minute ventilation to carbon dioxide output) was also more impaired (38.0 ± 7.9 vs 36.2 ± 7.3; P = 0.043). Patients with autoimmune disorders had a higher risk of death or heart failure (HF) hospitalization compared with those without in adjusted analyses (HR: 1.95 [95% CI: 1.17-3.27]; P = 0.011) over a median follow-up of 3.0 years, which was primarily attributable to higher risk of HF hospitalization (HR: 2.87 [95% CI: 1.09-7.57]; P = 0.033). ConclusionsPatients with HFpEF and autoimmune disorders have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared with those without.

Bioinformatics identifies key genes and potential drugs for energy metabolism disorders in heart failure with dilated cardiomyopathy.

Background: Dysfunction in myocardial energy metabolism plays a vital role in the pathological process of Dilated Cardiomyopathy (DCM). However, the precise mechanisms remain unclear. This study aims to investigate the key molecular mechanisms of energy metabolism and potential therapeutic agents in the progression of dilated cardiomyopathy with heart failure. Methods: Gene expression profiles and clinical data for patients with dilated cardiomyopathy complicated by heart failure, as well as healthy controls, were sourced from the Gene Expression Omnibus (GEO) database. Gene sets associated with energy metabolism were downloaded from the Molecular Signatures Database (MSigDB) for subsequent analysis. Weighted Gene Co-expression Network Analysis (WGCNA) and differential expression analysis were employed to identify key modules and genes related to heart failure. Potential biological mechanisms were investigated through Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the construction of a competing endogenous RNA (ceRNA) network. Molecular docking simulations were then conducted to explore the binding affinity and conformation of potential therapeutic drugs with hub genes. Results: Analysis of the left ventricular tissue expression profiles revealed that, compared to healthy controls, patients with dilated cardiomyopathy exhibited 234 differentially expressed genes and 2 genes related to myocardial energy metabolism. Additionally, Benzoylaconine may serve as a potential therapeutic agent for the treatment of dilated cardiomyopathy. Conclusion: The study findings highlight the crucial role of myocardial energy metabolism in the progression of Dilated Cardiomyopathy. Notably, Benzoylaconine emerges as a potential candidate for treating Dilated Cardiomyopathy, potentially exerting its therapeutic effects by targeted modulation of myocardial energy metabolism through NRK and NT5.

Central apneas and cardiovascular diseases

Central apneas (CA) and periodic breathing (PB) are the most common related breathing disorders in heart failure, being observed in up to 50% of patients. Once considered only a sleep-related phenomenon, actually CA/PB occur across the whole 24 h period and their presence in the awake patient even in the upright position and during physical effort has been associated with a worse clinical profile and a greater mortality. Chemoreflex activation, circulatory time delay and altered plant gain are the pathophysiological determinants. While the use of guideline-recommended medical and device treatment represents the first step in the management of CA in heart failure patients, no specific therapy has been demonstrated to reduce CA-related impact on mortality. In particular, the use of non-invasive ventilation has yielded contradictory results in the context of large-scale randomized clinical trials. The design and testing of therapies targeting the pathophysiological triggers of CA, such as chemoreflex sensitivity, may prove valuable in the next future.

ANALYSIS OF THE INFLUENCE OF CARDIOLOGICAL ANAMYST ON THE RESULTS OF SURGICAL TREATMENT OF POST-TRAUMATIC PERICARDITIS

Abstract. Introduction. Post-traumatic pericarditis is the most common and most discussed disease of the pericardium. Today there are no studies aimed at identifying the causes and mechanisms of occurrence of certain forms of pericarditis and specific recommendations for their diagnosis and treatment. The lack of unified tactics in the treatment of post-traumatic pericarditis determines the need for different approaches and attitudes in medical institutions, in particular, monitoring the treatment of the wounded and injured, taking into account diseases of the circulatory system, as well as injuries and diseases of the myocardium.&#x0D; The Aim is to identify the patterns of development and to establish the features of hemodynamic disorders in heart failure in victims with post-traumatic pericarditis.&#x0D; Materials and methods. 62 cases of post-traumatic pericarditis have been investigated. They have been divided into 2 groups. The patients of group 1 (n = 29) had no cardiac anamnesis at the time of injury, their average age was (58.7±9.4) years (M±σ). The patients of group 2 (n = 33) had an anamnesis of chronic coronary heart disease (CCHD), their average age was 60.0±9.6 years (between groups p = 0.6). All patients underwent thoracoscopic pericardotomy, sanation and drainage of the pericardial and pleural cavities. The level of troponin I (TnI) as an indicator of myocardial damage, the level of NT-proBNP as an indicator of the degree of heart failure, as well as indicators of cardio and central hemodynamics and their energy component have been studied: stroke index (SI), ejection fraction (EF), cardiac index (CI), specific peripheral vascular resistance (SPVR), systemic perfusion pressure (SPP), which is equal to the difference between average arterial and central venous pressure, blood flow power (BFP), oxygen reserve (OR) and circulatory reserve (CR). Stages of research: 1) admission; 2) 3rd day; 3) 7th day.&#x0D; Results and discussion. Myocardial injury affected the state of the myocardium much more significantly than previous CCHD. The use of energy indicators of blood circulation allows to evaluate more accurately its condition. Surgical intervention improves the condition of the circulatory system, but the previous heart failure on the background of the CCHD reduces the results of treatment.

Anxiety in heart failure patients and its association with socio-demographic and clinical characteristics: a cross-sectional study.

Background:Anxiety is one of the most frequent psychiatric disorders in heart failure (HF) patients. However, it is often neglected in clinical practice and studies about the particular relationship with the New York Heart Association (NYHA) classes for HF are scarce. In this context, this study aims to analyze the presence of anxiety symptoms in HF outpatients and also its association with sociodemographic and clinical characteristics of these patients.Methods:This cross-sectional study is part of the longitudinal Deus Ex-Machina project (NORTE-01-0145-FEDER-000026). HF patients were recruited at an outpatient clinic at a University Hospital. Patients with inability to communicate, severe visual/hearing impairment, or NYHA class IV were excluded. Sociodemographic data and NYHA class were registered. Anxiety was assessed with the 7-item Generalized Anxiety Disorders Scale (with a score ≥10 clinically relevant anxiety). Patients with and without anxiety were compared regarding socio-demographic and clinical variables.Results:The sample (n = 136) had a median age of 59years (Q1: 49; Q3: 68), 66.2% were male and 31.6% presented clinically relevant anxiety. A higher percentage of HF patients with anxiety had psychiatric disorders (58.1% vs 26.9%; P = .001), psychotropic medication (62.8% vs 30.1%; P = .001), and depression (60.5% vs 9.7%; P< .001). No significant differences were found regarding the remaining variables, including NYHA classes.Conclusions:A substantial proportion of HF patients present clinically relevant anxiety, particularly those with psychiatric history, depressive symptoms, or under psychotropic medication. Therefore, integrating routine screening and treatment of this comorbidity in clinical practice is of utmost importance. Further studies are needed to clarify the association of anxiety with HF.

Anti‐depressant lithium compounds reliefs cardiorespiratory disturbances and improves cardiac function in experimental non‐ischemic heart failure

Non‐ischemic heart failure (HF) is a complex medical problem with a high incidence among the older population. While several efforts have been made to improve HF outcomes there is an urgent need for new strategies to reduce mortality rates. Sympathoexcitation and disordered breathing are both considered hallmarks of HF and are closely related to disease progression. Lithium salts has been largely used as anti‐depressants; however, lithium compounds also showed several pleiotropic effects some of them linked to the origin of cardiorespiratory disorders in HF (i.e. oxidative stress). Accordingly, using drug repurposing strategy we aimed to define whether lithium treatment improve cardiorespiratory function in experimental HF. Male Sprague‐Dawley rats underwent volume overload to induce non‐ischemic HF. Four weeks after HF induction, an osmotic minipump containing lithium chloride (Li+, 2 meq/Kg/day) was subcutaneously implanted for drug delivery. Cardiac autonomic and baroreflex function, ventilatory chemoreflex drive and disordered breathing were evaluated after 4 weeks of Li+ treatment in freely moving rats. In addition, cardiac function was determine using PV‐loops. Compared to Sham rats, HF animals displayed autonomic imbalance, reduced baroreflex sensitivity, higher incidence of cardiac arrhythmias, enhanced central chemoreflex and breathing disorders. Cardiac diastolic dysfunction was evident in HF animals compared to Sham animals. HF rats that underwent Li+ treatment showed significant (p&lt;0.05) improvements in cardiac autonomic function as evidenced by reduced low‐to‐high frequency ratio of heart rate variability (LF/HF: 2.8 ± 0.3 vs. 0.9 ± 0.4; HF+Veh vs. HF+Li+), baroreflex sensitivity (BRS: 2.0 ± 0.5 vs. 5.8 ± 1.0 ms/mmHg; HF+Veh vs. HF+Li+) and reduced cardiac arrhythmogenesis (PVC: 220 ± 50 vs. 30 ± 10 events/h; HF+Veh vs. HF+Li+). Furthermore, Li+ treatment in HF completely normalized central chemoreflex drive. Indeed, hypercapnic ventilatory responses obtained in HF+Li+ rats were undistinguishable from the ones obtained in Sham rats (HCVR: 1.7 ± 0.4 vs. 2.0 ± 0.4 DVe/FiCO2; HF+Veh vs. HF+Li+). Also, breathing disorders (i.e. apneas/hypopneas) were markedly reduced by Li+ treatment in HF (AHI: 8.5 ± 1.0 vs. 3.7 ± 0.8; HF+Veh vs. HF+Li+). Lastly, HF+Li+ treated rats displayed marked improvements in cardiac diastolic function (~2.5‐fold reduction in EDPVR) compared to HF+Veh treated rats. We found that the beneficial effects of Li+were partially associated with upregulation of the Nrf2 pathway and related antioxidant genes (i.e. SOD2), reductions in tissue oxidative stress and decreases in the expression of pro‐inflammatory cytokines (i.e. TNF‐a) in HF rats. Our results support the notion that lithium compounds may offer new avenues for the treatment of cardiorespiratory disorders and cardiac diastolic dysfunction in non‐ischemic HF.

Reduced expression of SOD2 in the Retrotrapezoid nucleus is associated with enhanced ventilatory chemoreception: implications for breathing disorders in heart failure

Enhanced chemoreflex drive and irregular breathing patterns are both hallmarks in heart failure (HF). The Retrotrapezoid nucleus (RTN), a main area for central chemoreception, contribute to maintain both heightened chemoreflex drive and irregular breathing in experimental HF. Recently, we found that high levels of reactive oxygen species (ROS) within the RTN of HF rats were closely linked to the enhanced central chemoreflex and the generation of breathing disorders. Despite this evidence, the effects of ROS on RTN‐mediated chemoreception and the precise mechanism(s) associated with ROS generation in the RTN has not been previously studied. However, pro/anti‐oxidant enzymes gene screening in RTN from HF rats revealed reduce expression of super oxide dismutase 2 (SOD2). Therefore, in the present study we aimed to determine whether reductions in SOD2 expression in healthy subjects resembles i) high RTN ROS levels, ii) heightened chemoreflex drive, and iii) generation of breathings disorders observed in HF animals. Accordingly, breathing function and central chemoreflex drive were assessed in freely moving heterozygous SOD2+/‐ mice by unrestrained whole‐body plethysmography. ROS levels were determined in brainstem sections containing the RTN using dihydroethidium staining. SOD2 protein expression and tissue localization were determined by immunoblot and immunofluorescence, respectively. SOD2+/‐ mice displayed reduced SOD2 protein expression (65.6 ± 3.2 vs. 100.0 ± 5.8 %; SOD2+/‐ vs. WT, respectively) and high ROS levels at the RTN compared to WT littermates (2.50 ± 0.46 vs. 1.00 ± 0.05 a.u.; SOD2+/‐ vs. WT, respectively). In addition, SOD2+/‐mice displayed an exacerbated ventilatory response to hypercapnia compared to WT mice (3.5 ± 0.2 vs. 1.9 ± 0.2 ml/min/10g; SOD2+/‐ vs. WT, respectively). Importantly, the latter was closely linked to RTN ROS production since a positive correlation (p&lt;0.05) between ROS levels and the hypercapnic ventilatory response was found only in SOD2+/‐animals. Furthermore, SOD2+/‐ mice showed overt signs of disordered breathing while resting at eupneic conditions compared to WT mice as evidenced by large increases in ventilatory instability and apneas/hypoapneas incidence (AHI: 7.7 ± 0.9 vs. 3.4 ± 0.6 events/hr; SOD2+/‐ vs. WT, respectively). Lastly, we found that SOD2 expression is preferentially confined to RTN neurons rather than to medullary astrocytes. Our results shows that reductions in the SOD2 gene expression in healthy rodents mimic the respiratory phenotype observed in experimental HF and suggests that reduced expression of SOD2 within the RTN of HF animals may account for the local increases in ROS production, the enhanced central chemoreflex drive and the generation/maintenance of irregular breathing patterns.

Chapter 15 - Sleep and breathing disorders in heart failure

Sleep disorders are prevalent in heart failure and include insomnia, poor sleep architecture, periodic limb movements and periodic breathing, and encompass both obstructive (OSA) and central sleep apnea (CSA). Polysomnographic studies show excess light sleep and poor sleep efficiency particularly in those with heart failure. Multiple studies of consecutive patients with heart failure show that about 50% of patients suffer from either OSA or CSA. While asleep, acute pathological consequences of apneas and hypopneas include altered blood gases, sleep fragmentation, and large negative swings in intrathoracic pressure. These pathological consequences are qualitatively similar in both types of sleep apnea, though worse in OSA than CSA. Sleep apnea results in oxidative stress, inflammation, and endothelial dysfunction, best documented in OSA. Multiple studies show that both OSA and CSA are associated with excess hospital readmissions and premature mortality. However, no randomized controlled trial (RCT) has been reported for OSA, but sensitivity analysis of two randomized controlled trials has concluded that use of positive airway pressure devices is associated with excess mortality in patients with heart failure and CSA. Phrenic nerve stimulation has shown improvement in sleep apnea events and daytime sleepiness; however, no randomized controlled trials have demonstrated improvement in survival in patients with heart failure. The correct identification and treatment of heart failure patients with sleep and breathing disorders could affect the long-term outcomes of these patients.

Neuroinflammation and Microglial Activation in The Central Amygdala in Rats with Heart Failure

Cardiovascular diseases (CVDs), such as heart failure (HF) are the most common cause of death globally. Moreover, clinical studies support a high degree of comorbidity between CVDs cognitive impairment, and emotional distress, with 20–40% of all HF patients displaying depression and anxiety levels significantly higher than the healthy population. Still, the precise underlying mechanisms causing those cognitive and emotional impairments remain elusive. The paraventricular nucleus of the hypothalamus (PVN) is a key brain structure involved in emotional control and directly communicates with the central lateral part of the amygdala (CeA), which actively participates in the regulation of emotion and fear memories. While markers of neuroinflammation (NI) have been previously described in the PVN of HF rats, it is at present unknown whether the CeA is also affected. To address this question, we used an ischemic HF rat model (ejection fraction &lt;35%). We developed a comprehensive quantitative microglial profiler using the IMARIS software along with immunohistochemical staining with the microglial marker IBA‐1 to assess changes in various microglial parameters indicative of different microglia activity stages. At early stages of the established HF (8wks post‐surgery), we found elevated indexes of microglial activation in the PVN compared to sham controls (15.4% decrease in surface area, 29.9% decrease in cell volume, 15.5% decrease in filament length and 35.1% increase in IBA‐1 immunoreactivity intensity, p&lt;0.001 in all cases). These changes became more pronounced at later (14wks) stages of the disease. While no changes were observed in the CeA at the early stage, significant changes were observed at 14wks after HF compared to sham controls (21.2% increase in cell volume, 9.7% decrease in filament length and 12.3% increase in IBA‐1 immunoreactivity intensity, p&lt;0.05 in all cases). These morphometric changes are indicative of de‐ramification and somatic swelling of microglial cells. These findings were corroborated by elevated mRNA levels of IBA‐1, TNF‐a, IL‐1β and IL‐6 measured via qPCR in PVN and CeA punches from HF rats. Importantly, no microglial changes were observed in cortical areas suggesting that HF‐induced NI was not a diffuse phenomenon affecting the entire brain. To the best of our knowledge, our results highlight for the first time that in addition to the PVN, HF also results in a robust microglial cell activation in the CeA, a critical forebrain region involved in emotion and cognition. NI‐related changes in the CeA occurred at a later stage of the disease, and could potentially contribute to cognitive impairment and mood disorders in HF patients.Support or Funding InformationNational Institutes of Health grants R01NS094640 and R01HL090948 to JES

Neurocognitive Disorders in Heart Failure: Novel Pathophysiological Mechanisms Underpinning Memory Loss and Learning Impairment.

Heart failure (HF) is a major public health issue affecting more than 26 million people worldwide. HF is the most common cardiovascular disease in elder population; and it is associated with neurocognitive function decline, which represent underlying brain pathology diminishing learning and memory faculties. Both HF and neurocognitive impairment are associated with recurrent hospitalization episodes and increased mortality rate in older people, but particularly when they occur simultaneously. Overall, the published studies seem to confirm that HF patients display functional impairments relating to attention, memory, concentration, learning, and executive functioning compared with age-matched controls. However, little is known about the molecular mechanisms underpinning neurocognitive decline in HF. The present review round step recent evidence related to the possible molecular mechanism involved in the establishment of neurocognitive disorders during HF. We will make a special focus on cerebral ischemia, neuroinflammation and oxidative stress, Wnt signaling, and mitochondrial DNA alterations as possible mechanisms associated with cognitive decline in HF. Also, we provide an integrative mechanism linking pathophysiological hallmarks of altered cardiorespiratory control and the development of cognitive dysfunction in HF patients. Graphical Abstract Main molecular mechanisms involved in the establishment of cognitive impairment during heart failure. Heart failure is characterized by chronic activation of brain areas responsible for increasing cardiac sympathetic load. In addition, HF patients also show neurocognitive impairment, suggesting that the overall mechanisms that underpin cardiac sympathoexcitation may be related to the development of cognitive disorders in HF. In low cardiac output, HF cerebral infarction due to cardiac mural emboli and cerebral ischemia due to chronic or intermittent cerebral hypoperfusion has been described as a major mechanism related to the development of CI. In addition, while acute norepinephrine (NE) release may be relevant to induce neural plasticity in the hippocampus, chronic or tonic release of NE may exert the opposite effects due to desensitization of the adrenergic signaling pathway due to receptor internalization. Enhanced chemoreflex drive is a major source of sympathoexcitation in HF, and this phenomenon elevates brain ROS levels and induces neuroinflammation through breathing instability. Importantly, both oxidative stress and neuroinflammation can induce mitochondrial dysfunction and vice versa. Then, this ROS inflammatory pathway may propagate within the brain and potentially contribute to the development of cognitive impairment in HF through the activation/inhibition of key molecular pathways involved in neurocognitive decline such as the Wnt signaling pathway.

Metabolic disorders in heart failure and cancer.

In an aging population, the number of patients affected by heart failure and cancer is constantly increasing and together these two conditions account for more than 50% of all deaths worldwide. Both diseases share similar risk factors including smoking, obesity, and hypertension. Presenting symptoms may also be similar, with patients frequently complaining of dyspnea, fatigue, and anorexia. Many affected patients, especially those with more advanced heart failure or cancer, suffer also from metabolic disorders. These can lead eventually to muscle wasting, sarcopenia, and cachexia. These complications are associated with increased morbidity, a poorer quality of life, a worse prognosis and indeed they represent an independent risk factor for the advancement of the underlying disease itself. Very few therapeutic options have been established to treat these co‐morbidities. For sarcopenia the only validated treatment is resistance training. Moreover, there is currently no guideline recommended therapy for the treatment of cachexia. New treatment strategies are urgently needed to prevent and treat muscle and wasting disorders in patients with chronic diseases such as cancer and chronic heart failure.

Depression, Anxiety, and Cognitive Impairment : Comorbid Mental Health Disorders in Heart Failure.

Depression, anxiety, and cognitive impairment constitute established risk markers for incident cardiovascular disease (CVD) and are associated with impaired life expectancy and quality of life and high hospitalization rates and healthcare expenditure. This review summarizes current knowledge about mental health disorders in patients with CVD and heart failure (HF). Emerging evidence suggests various shared pathophysiological mechanisms between psychological comorbidities and CVD (e.g., systemic inflammation and autonomic dysfunction). Bi-directional interactions involving the central nervous and cardiovascular systems may help explain the rising prevalence of comorbid mood disorders with increasing CVD severity and support the concept of alternative pathophysiological mechanisms in the presence of severe somatic illness, making symptoms less responsive or unresponsive to psychotropic pharmacotherapy. Considering high prevalence and negative impact of psychological comorbidities in CVD and HF, routine care should integrate screening for these conditions. Multidisciplinary treatment approaches with active patient participation in disease management were shown to improve outcomes. However, better understanding of factors mediating the adverse prognostic effects of mood disorders is needed. This might enable more targeted treatment and possibly also facilitate better understanding of the pathophysiological mechanisms driving CVD.

Depression and Anxiety in Heart Failure: A Review.

After participating in this activity, learners should be better able to:• Identify the relationships between depression, anxiety, and heart failure (HF).• Assess methods for accurately diagnosing depression and anxiety disorders in patients with HF.• Evaluate current evidence for treatment of anxiety and depression in patients with HF. In patients with heart failure (HF), depression and anxiety disorders are common and associated with adverse outcomes such as reduced adherence to treatment, poor function, increased hospitalizations, and elevated mortality. Despite the adverse impact of these disorders, anxiety and depression remain underdiagnosed and undertreated in HF patients. We performed a targeted literature review to (1) identify associations between depression, anxiety, and HF, (2) examine mechanisms mediating relationships between these conditions and medical outcomes, (3) identify methods for accurately diagnosing depression and anxiety disorders in HF, and (4) review current evidence for treatments of these conditions in this population. Both depression and anxiety disorders are associated with the development and progression of HF, including increased rates of mortality, likely mediated through both physiologic and behavioral mechanisms. Given the overlap between cardiac and psychiatric symptoms, accurately diagnosing depression or anxiety disorders in HF patients can be challenging. Adherence to formal diagnostic criteria and utilization of a clinical interview are the best courses of action in the evaluation process. There is limited evidence for the efficacy of pharmacologic and psychotherapy in patients with HF. However, cognitive-behavioral therapy has been shown to improve mental health outcomes in patients with HF, and selective serotonin reuptake inhibitors appear safe in this cohort. Depression and anxiety disorders in HF patients are common, underrecognized, and linked to adverse outcomes. Further research to improve detection and develop effective treatments for these disorders in HF patients is badly needed.

Positive Airway Pressure for Sleep-Related Breathing Disorders in Heart Failure—Overview and Discussion of Potential Mechanisms of Harm

The impact of positive airway pressure (PAP) therapies on cardiovascular outcome in obstructive sleep apnea (OSA) and central sleep apnea (CSA) is currently under debate. The goal of this review is to critically analyze the current findings and discuss hypotheses on benefits or even harm in patients with heart failure (HF). While PAP sufficiently improves OSA, symptoms and cardiac parameters, the SAVE trial failed to show survival benefits. However, it was limited due to low adherence, non-sleepy population and maximal cardiac pre-treatment. SERVE-HF showed increased mortality in secondary analysis in patients with severe systolic HF with predominant CSA under adaptive servo-ventilation (ASV). Criticism of the trial emanated from high crossover, low compliance, use of older devices, and contradictory beneficial results in other studies. As sudden cardiac deaths was the reported main cause of mortality, influences of pre-medication and methods of pressure support on cardiac instability may have contributed to the pathogenesis. OSA and CSA are main risk factors for poor outcome in cardiovascular disease. However, the effect of CPAP and ASV on cardiovascular comorbidities and prognosis requires further evaluation. Further insights from ongoing trials are urgently needed to clarify benefits and risk.

Acuracy and Concordance of Anthropometric Indicators and Body Composition in Heart Failure

Abstract Background: Anabolic/catabolic disorder in heart failure (HF) favors cardiac cachexia, implying a reduction in HF survival. Objectives: To assess the accuracy and concordance of the diagnosis of protein malnutrition and excess fat among the anthropometric and body composition methods in individuals with HF. Method: A study of accuracy that included 60 individuals with HF. Body mass index (BMI), arm circumference (AC), triceps skinfold thickness (TST), adductor pollicis muscle thickness (APMT), arm muscle circumference (AMC) and corrected arm muscle area (cAMA). Fat free mass index (FFMI) and body fat percentage (BF%), obtained by electrical bioimpedance (EBI), were used to compare the diagnosis of protein malnutrition and excess fat. Accuracy was assessed by calculating sensitivity, specificity, positive and negative predictive value. The concordance of the EBI diagnosis and other methods was performed by the chi-square test and kappa (k) statistic, where p<0.05 was considered significant. Results: Higher frequencies of protein malnutrition were identified by cAMA and AMC, and excess fat by BF%. BMI presented low sensitivity (43%) and accuracy (38.5%), with moderate concordance (0.50). AMC sensitivity was 86%, accuracy 66.4%, and acceptable concordance (0.36) compared to FFMI. Similar percentages of moderate sensitivity and low accuracy were observed for TST and BMI. Conclusion: AMC may be useful to identify protein malnutrition and TST has not been adequate to diagnose adiposity. BMI was not sensitive to assess muscle and adipose reserve. EBI was more accurate.

Obstructive Ventilatory Disorder in Heart Failure-Caused by the Heart or the Lung?

Heart failure (HF) is a clinical syndrome frequently associated with airway obstruction, either as a respiratory comorbidity or as a direct consequence of HF pathophysiology. Recognizing the relative contribution of an underlying airway disease as opposed to airway obstruction due to volume overload and left atrial pressure elevation is of importance for the appropriate management of patients affected by HF. This review focuses on "les liaisons dangereuses" between the heart and the lungs, outlying recent advances linking in a vicious circle of chronic obstructive lung disease (COPD) and obstructive sleep apnea (OSA) on one side and HF on the other side. It also discusses the role of pivotal diagnostic tools such as pulmonary function tests and cardiopulmonary exercise test to determine the contribution of HF and COPD to symptoms and clinical status. Treatment implications are discussed as well.

Frequent Periodic Leg Movements during Sleep Is an Unrecognized Sleep Disorder in Heart Failure: A Case Report

Frequent Periodic Leg Movements during Sleep Is an Unrecognized Sleep Disorder in Heart Failure: A Case Report

RATIONALE FOR APPLICATION, AND BENEFITS OF TRIMETAZIDINE IN HEART FAILURE BY ITS INFLUENCE OF MYOCARDIUM METABOLISM

Heart failure (HF) is systemic and multiple organ syndrome, with metabolic insufficiency as one of its main causes. Heart metabolism disorders in HF activate other processes that futher worsens progression of the disease. Recent data shows that correction of energy metabolism in the heart by suppression of fatty acids (FA) oxydation and/or increase of glucose oxydation is one of promising approaches in HF patient’s treatment. Clinical studies showed that addition of trimetazidine to standard medication therapy improves sympthoms, cardiac function and prognosis in HF patients, not influencing negatively hemodynamics. The review is focused on rationale for and clinical benefits of trimetazidine application according to its influence on myocardial metabolism in HF. Also a very high level of preparedness of the drug to inclusion into main guidelines on HF is pointed on.

Regulating PPARδ signaling as a potential therapeutic strategy for skeletal muscle disorders in heart failure

despite remarkable improvements in cardiac mortality rates during the past decades ([4][1]), poor quality of life remains a major concern for patients with heart failure. One of the determinants of quality of life is exercise tolerance ([6][2]). Limited exercise capacity can result from multiple