Deciphering mortality risk of diabetes medications in heart failure patients with diabetes mellitus under triple guideline-directed medical therapy.

BACKGROUND: Scientific evidence regarding the impact of different combinations of diabetes medications in heart failure patients with diabetes mellitus (HFwDM) remains limited. AIM: We aimed to investigate the effect of monotherapy and combination therapy for DM on all-cause mortality in HFwDM under triple guideline-directed medical therapy (GDMT). METHOD: This nationwide retrospective cohort study included adult HFwDM under triple GDMT between January 1, 2016 and December 31, 2022.We collected the data from the National Electronic Database of the Turkish Ministry of Health.We created various combination including different diabetes medications based on the current guidelines for DM.The primary endpoint was all-cause mortality. RESULTS: A total of 321,525 HFwDM under triple GDMT (female:49%, median age:68[61-75] years) were included. The highest rate of prescribed combination therapy was metformin and sulfonylureas (n = 55,266). In Cox regression analysis, insülin monotherapy had the highest risk for all-cause mortality (HR:2.25, 95CI%:2.06 - 2.45), whereas combination therapy including metformin, SGLT2i, and sulfonylureas provided the most beneficial effect on survival (HR:0.29, 95CI%:0.22-0.39) when compared to patients not receiving diabetes medication. Among patients taking diabetes medications, the inclusion of SGLT2i demonstrated a survival benefit (p < 0.05), despite concurrent use of volume-retaining medications such as insulin and thiazolidinediones. Conversely, combinations of diabetes medications without SGLT2i did not demonstrate any survival benefit compared to patients not taking diabetes medication (p > 0.05). CONCLUSION: This study underscored the use of SGLT2i as monotherapy or as a part of combination diabetes medications to improve survival among HFwDM, while also highlighting that combinations lacking SGLT2i did not confer any survival benefit.

Digoxin is Not Related to Mortality in Patients with Heart Failure: Results from the SELFIE-TR Registry.

AIMS: Digoxin has been used in the treatment for heart failure for centuries, but the role of this drug in the modern era is controversial. A particular concern is the recent observational findings suggesting an increase in all-cause mortality with digoxin, although such observations suffer from biased results since these studies usually do not provide adequate compensation for the severity of disease. Using a nationwide registry database, we aimed to investigate whether digoxin is associated with 1-year all-cause mortality in patients with heart failure irrespective of phenotype. METHODS: A total of 1014 out of 1054 patients in the registry, of whom 110 patients were on digoxin, were included in the study. Multivariable adjustments were done and propensity scores were calculated for various prognostic indicators, including signs and symptoms of heart failure and functional capacity. Crude mortality, mortality adjusted for covariates, mortality in the propensity score-matched cohort, and Bayesian factors (BFs) were analyzed. RESULTS: Crude 1-year mortality rate did not differ between patients on and off digoxin (17.3% vs 20.1%, log-rank p = 0.46), and digoxin was not related to mortality following multivariable adjustment (hazard ratio 0.87, 95% confidence interval 0.539-1.402, p = 0.57). Similarly, all-cause mortality was similar in 220 propensity-score adjusted patients (17.3% vs 20.0%, log-rank p = 0.55). On Bayesian analyses, there was moderate to strong evidence suggesting a lack of difference between in unmatched cohort (BF10 0.091) and weak-to-moderate evidence in the matched cohort (BF10 0.296). CONCLUSIONS: In this nationwide cohort, we did not find any evidence for an increased 1-year mortality in heart failure patients on digoxin.

The efficacy and safety of soluble guanylate cyclase modulation in patients with heart failure: a comprehensive meta-analysis of randomized controlled trials.

Soluble guanylate cyclase (sGC) modulation has been scrutinized in several disease states including heart failure (HF). Recently, it was shown that an sGC modulator improved HF-related hospitalization significantly, though, there was no benefit related to mortality. Herein, a comprehensive meta-analysis of randomized controlled trials (RCTs) for sGC modulation in HF patients was provided in agreement with the PRISMA statement. A total of 10 RCTs yielding 12 papers were included. There were 7526 patients with heart failure of each phenotype, 4253 in the sGC modulator group and 3273 in the placebo group. Use of sGC modulators in HF patients yielded no significant difference in the risk of all-cause mortality compared to placebo (RR = 0.97, 95% CI 0.88-1.08, p = 0.62). The use of sGC modulators was associated with a trend toward a considerable but non-significant increase in the incidence of SAEs (RR = 1.10, 95% CI 0.99-1.22, p = 0.07), as well as an increased incidence of hypotension and anemia. There was an overall neutral effect of sGC modulation on NT-proBNP levels, 6MWD and mortality, at a cost of slight increase in hypotension and anemia. Of note, the improvement in EQ-5D-based quality of life was significant. Hence, the benefit seems to be driven by distinctive domains of quality of life.

Association of soluble ST2 Level with 6-month Mortality and/or Recurrent Cardiovascular-Related Hospitalization in Pulmonary Embolism. / Associação do Nível de ST2 Solúvel com Mortalidade em 6 Meses e/ou Hospitalização Recorrente Relacionada a Doenças Cardiovasculares em Embolia Pulmonar.

BACKGROUND: The association of soluble suppression of tumorigenesis-2 (sST2) levels with prognosis in pulmonary embolism (PE) is unknown. OBJECTIVE: This study aimed to investigate the relationship between sST2 levels in patients with acute PE and 6-month mortality and recurrent hospitalizations. METHODS: This prospective study included 100 patients with acute PE. Patients were classified into two groups according to 6-month mortality and the presence of recurrent Cardiovascular-Related hospitalizations. Two groups were compared. A p-value of 0.05 was considered statistically significant. RESULTS: Soluble ST2 levels were significantly higher in the group with mortality and recurrent hospitalizations. (138.6 ng/mL (56.7-236.8) vs. 38 ng/mL (26.3-75.4); p<0.001) The best cut-off threshold for sST2 levels in the prediction of a composite outcome of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization was found to be >89.9 with a specificity of 90.6% and a sensitivity of 65.2%, according to the receiver operating characteristic curve (area under the curve = 0.798; 95% CI, 0.705-0.891; p <0.0001). After adjusting for confounding factors that were either statistically significant in the univariate analysis or for the variables correlated with the sST2 levels, sST2 level (OR = 1.019, 95% CI: 1.009-1.028, p 0.001) and C-reactive protein (CRP ) (OR = 1.010, 95% CI: 1.001-1.021, p = 0.046) continued to be significant predictors of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in the multiple logistic regression model via backward stepwise method. CONCLUSION: Soluble ST2 level seems to be a biomarker to predict 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in patients with acute PE.

FUNDAMENTO: A associação de supressão solúvel da tumorigênese-2 (sST2) com prognóstico em embolia pulmonar (EP) é desconhecida. OBJETIVO: Este estudo teve como objetivo investigar a relação entre os níveis de sST2 em pacientes com EP aguda e mortalidade em 6 meses e hospitalizações recorrentes. MÉTODOS: Este estudo prospectivo incluiu 100 pacientes com EP aguda. Os pacientes foram classificados em dois grupos de acordo com a mortalidade em 6 meses e a presença de hospitalizações recorrentes relacionadas a doenças cardiovasculares. Dois grupos foram comparados. Um valor de p de 0,05 foi considerado estatisticamente significativo. RESULTADOS: Os níveis de ST2 solúvel foram significativamente maiores no grupo com mortalidade e internações recorrentes. (138,6 ng/mL (56,7-236,8) vs. 38 ng/mL (26,3-75,4); p<0,001) O melhor limite de corte para níveis de sST2 na previsão de um desfecho composto de mortalidade em 6 meses e/ou a hospitalização recorrente relacionada a doenças cardiovasculares foi >89,9, com especificidade de 90,6% e sensibilidade de 65,2%, de acordo com a curva Receiver Operating Characteristic (área sob a curva = 0,798; IC 95%, 0,705­0,891; p <0,0001). Após ajuste para fatores de confusão que foram estatisticamente significativos na análise univariada ou para as variáveis correlacionadas com os níveis de sST2, nível de sST2 (OR = 1,019, IC 95%: 1,009-1,028, p 0,001) e proteína C reativa (PCR). (OR = 1,010, IC 95%: 1,001-1,021, p = 0,046) continuaram a ser preditores significativos de mortalidade em 6 meses e/ou hospitalização recorrente relacionada a doenças cardiovasculares no modelo de regressão logística múltipla através do método backward stepwise. CONCLUSÕES: O nível de ST2 solúvel parece ser um biomarcador para prever mortalidade em 6 meses e/ou hospitalização recorrente relacionada a doenças cardiovasculares em pacientes com EP aguda.

Patient Perception, Knowledge and Adaptation in The Management of Heart Failure: A Multicenter, Cross-Sectional, Observational, Questionnaire-Based Study: ADAPTATION HF.

OBJECTIVE: The aim of this study is to reveal the perception levels of heart failure (HF) patients about the disease, their adaptation to the disease process, their compliance with the treatment, and their knowledge and thoughts about the disease from the patient's perspective. METHOD: Patients with a diagnosis of HF for at least 6 months who applied to the cardiology clinics of 10 different centers were included in this cross-sectional, multicenter and questionnaire-based study. A questionnaire consisting of sections that included demographic information, evaluation of the patient's symptoms, knowledge and experience of clinical follow-up, knowledge of HF, compliance and awareness of treatment was applied to the patients. RESULTS: 504 patients with a mean age of 59.8 ± 14.9 years (M/F: 360/144, 71.4%/28.6%) were included in the study. 61.2% of the patients stated that they knew about HF disease before. Most of the patients knew that the complaints of shortness of breath, fatigue and palpitation could develop due to HF (95.4%; 92.7%; 89.7%, respectively). The patients reported that they were mostly worried about not being able to provide their own self-care without the support of another person (67.5%). While the majority of patients (37.6%) thought that the worst disease was to have a cerebrovascular disease; only 10.9% stated that HF was the worst disease. While 98.8% of the patients stated that they used HF drugs regularly, a relatively large part of the patients did not know that the drugs were effective on kidney functions (68.5%) and blood pressure (76.9%). In the daily practice of the patients, the rate of weight follow-up was 35.5%, the rate of blood pressure monitoring was 26.9%, and the rate of patients who exercised was 27%. Among the patients, 73.3% said that they pay attention to the amount of salt they take with diet, and 33.5% have a completely salt.free diet. There was no difference between the groups with low and high knowledge scores in terms of Pittsburgh Sleep Quality Index (P > 0.005). The knowledge level score was significantly higher in patients with previous myocardial infarction (P = 0.002). CONCLUSION: Most of the HF patients participating in the study are aware of the signs and symptoms of HF, follow the recommendations of their physicians, and use drugs regularly. These patients should have more information about blood pressure monitoring, weight monitoring, diet and sodium restriction, exercise, which are included in the non-pharmacological part of treatment management.

Navigating Heart Failure: Unveiling Sex Disparities in Guideline-Directed Medical Therapy Combinations.

Major heart failure (HF) trials remain insufficient in terms of assessing the differences in clinical characteristics, biomarkers, treatment efficacy, and safety because of the under-representation of women. The study aimed to present sex-related disparities in HF management, including differences in demographics, co-morbidities, cardiac biomarkers, prescribed medications, and treatment outcomes. The study utilized anonymized data from the Turkish Ministry of Health's National Electronic Database between January 1, 2016, and December 31, 2022. The cohort analysis included 2,501,231 adult patients with HF. Specific therapeutic combinations were analyzed using a Cox regression model to obtain relative risk reduction for all-cause death. The primary end point was all-cause mortality. In the cohort, 48.7% (n = 1,218,911) were male, whereas 51.3% (n = 1,282,320) were female. Female patients exhibited a higher median age (71 vs 68 years) and manifested higher prevalence of diabetes mellitus, anemia, atrial fibrillation, anxiety, and ischemic stroke. Male patients demonstrated higher rates of previous myocardial infarction, dyslipidemia, chronic obstructive pulmonary disease, and chronic kidney disease. Higher concentrations of natriuretic peptides were observed in female patients. Renin-angiotensin aldosterone inhibitor, ß blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitor (SGLT2i), and ivabradine were more commonly prescribed in male patients, whereas loop diuretics, digoxin, and ferric carboxymaltose were more frequent in female patients. Male patients had higher rates of cardiac resynchronization therapy and implantable cardioverter defibrillator implantation rates. All-cause mortality and hospitalization rates were higher in male patients. Compared with monotherapy, all combinations, including SGLT2i, showed a beneficial effect on all-cause mortality in both female and male patients with HF. In hospitalized patients with HF, the addition of digoxin to renin-angiotensin aldosterone inhibitor, mineralocorticoid receptor antagonists, and ß blockers was superior to monotherapy regarding all-cause mortality in female patients with HF compared with male patients with HF. In conclusion, this study highlights that sex-specific responses to HF medication combinations compared with monotherapy and differences in co-morbidities underscore the importance of tailored management strategies. Digoxin showed a contrasting effect on all-cause mortality between both sexes after hospitalization, whereas SGLT2i exhibited a consistent beneficial effect in both sexes when added to all combinations.

Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care.

Exploring Regional Disparities in Heart Failure Epidemiology and Outcomes: A Comprehensive Study Across Geographical Regions in Türkiye.

Background: Heart failure (HF) is a common condition that affects 1-3% of the general population. Its prevalence exhibits notable international and intranational disparities, partly explained by socioeconomic status, religion, ethnic diversity, and geographic factors. A comprehensive understanding of the epidemiological symptoms of HF in different regions of Türkiye has yet to be revealed. Aims: To examine epidemiological data from 2016 to 2022, focusing on crucial patient characteristics and geographical regions, to determine the incidence and prevalence of HF in Türkiye across seven diverse geographical regions. Study Design: A nationwide population-based retrospective cohort study. Methods: The comprehensive National Electronic Database of the Turkish Ministry of Health was used in this study to obtain data that covers the whole Turkish population from January 1, 2016, to December 31, 2022. The International Classification of Diseases-10 (ICD-10) codes were used to identify adults with HF (n = 2,701,099) and associated comorbidities. Türkiye is divided into seven geographically distinct regions. Epidemiological characteristics and survival data of these regions were analyzed separately. All-cause mortality was set as the primary outcome. Results: In , the total estimated prevalence of adult patients with HF is 2.939%, ranging from 2.442% in Southeastern Anatolia to 4.382% in the Black Sea Region. Except for the Eastern Anatolia Region, the three most often reported comorbidities were hypertension, dyslipidemia, and anxiety disorders. The rates of prescribing guideline-directed medical therapy (GDMT) for HF and other medications varied significantly. GDMT prescription rates were lowest in the Eastern Anatolia Region (82.6% for beta-blockers, 48.7% for RASi, 31.8% for mineralocorticoid receptor antagonists, and 9.4% for SGLT2i). The Mediterranean and Aegean regions had the highest median N-terminal brain natriuretic peptide (NT-proBNP) levels of 1,990,0 pg/ml (518.0-6,636,0) and 1,441,0 pg/ml (363.0-5,000,0), respectively. From 2016 to 2022, 915,897 (33.9%) of 2,701,099 patients died. The Eastern Anatolia Region had the lowest all-cause mortality rate of 26.5%, whereas the Black Sea Region had the highest all-cause mortality rate of 35.3%. Conclusion: Our real-world analysis revealed geographic disparities in HF characteristics, such as decreased mortality in socioeconomically challenged regions. Higher stress susceptibility in developed regions may increase the likelihood of adverse outcomes.

Expert Recommendations to Bridge Gaps in Heart Failure Patient Support in the Middle East and Africa Region.

Heart failure (HF) remains a serious health and socioeconomic problem in the Middle East and Africa (MEA). The age-standardized prevalence rate for HF in the MEA region is higher compared to countries in Eastern Europe, Latin America, and Southeast Asia. Also cardiovascular-related deaths remain high compared to their global counterparts. Moreover, in MEA, 66% of HF readmissions are elicited by potentially preventable factors, including delay in seeking medical attention, nonadherence to HF medication, suboptimal discharge planning, inadequate follow-up, and poor social support. Patient support in the form of activation, counseling, and caregiver education has been shown to improve outcomes in patients with HF. A multidisciplinary meeting with experts from different countries across the MEA region was convened to identify the current gaps and unmet needs for patient support for HF in the region. The panel provided insights into the real-world challenges in HF patient support and contributed strategic recommendations for optimizing HF care.

Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Right-sided heart failure and tricuspid regurgitation are common and strongly associated with poor quality of life and an increased risk of heart failure hospitalizations and death. While medical therapy for right-sided heart failure is limited, treatment options for tricuspid regurgitation include surgery and, based on recent developments, several transcatheter interventions. However, the patients who might benefit from tricuspid valve interventions are yet unknown, as is the ideal time for these treatments given the paucity of clinical evidence. In this context, it is crucial to elucidate aetiology and pathophysiological mechanisms leading to right-sided heart failure and tricuspid regurgitation in order to recognize when tricuspid regurgitation is a mere bystander and when it can cause or contribute to heart failure progression. Notably, early identification of right heart failure and tricuspid regurgitation may be crucial and optimal management requires knowledge about the different mechanisms and causes, clinical course and presentation, as well as possible treatment options. The aim of this clinical consensus statement is to summarize current knowledge about epidemiology, pathophysiology and treatment of tricuspid regurgitation in right-sided heart failure providing practical suggestions for patient identification and management.

Trends in heart failure between 2016 and 2022 in Türkiye (TRends-HF): a nationwide retrospective cohort study of 85 million individuals across entire population of all ages.

Background: Data on the burden of heart failure (HF) outside western countries are limited, but available data suggest it may present differently in other countries. The aim of this study was to examine the incidence, prevalence, and survival rates of HF in Türkiye, with a specific focus on how these rates vary according to age, sex, comorbidities, and socioeconomic status (SES). Methods: We harnessed the extensive National Electronic Database of the Turkish Ministry of Health, covering Turkey's entire population from January 1, 2016, to December 31, 2022, to identify 2,722,151 cases of HF and their associated comorbidities using ICD-10 codes. Analyzing the primary endpoint of all-cause mortality, our study utilized anonymized data to examine patient demographics, comorbidities, socioeconomic status, and survival patterns, employing statistical techniques to delve into relationships and trends. The data were segmented by gender, socioeconomic status, and age, involving cross-tabulations and statistical metrics to explore connections, odds ratios, and survival rates. Findings: The estimated prevalence of HF was 2.114% in Türkiye at the end of 2022, with an annual incidence ranging between 3.00 and 6.06 per 1000 person years. Females were older than males (69.8 ± 13.9 years vs. 66.8 ± 13.9 years, respectively). The most common comorbidities were congenital heart diseases and anemia under the age of 20, and hypertension and atherosclerotic cardiovascular disease in the adult population. Only 23.6% (643,159/2,722,151) of patients were treated with any triple guideline-directed medical therapy (GDMT) and 3.6% (96,751/2,722,151) of patients were on quadruple GDMT. The survival rates for patients with HF at 1, 5, and 7 years were 83.3% (95% CI: 83.2-83.3), 61.5% (95% CI: 61.4-61.6), and 57.7% (95% CI: 57.6-57.8) among females, and 82.1% (95% CI: 82.0-82.2), 58.2% (95% CI: 58.1-58.3), and 54.2% (95% CI: 54.0-54.3) among males. Despite a tendency for an increase from the highest to the lowest SES, the prevalence of HF and mortality were paradoxically lowest in the lowest SES region. Interpretation: The prevalence, incidence, and survival rates of HF in Türkiye were comparable to western countries, despite the notable difference of HF onset occurring 8-10 years earlier in the Turkish population. Drug usage statistics indicate there is a need for effective strategies to improve treatment with GDMT. Funding: None.

Regional expert opinion: Management of heart failure with preserved ejection fraction in the Middle East, North Africa and Turkey.

Although epidemiological data on heart failure (HF) with preserved ejection fraction (HFpEF) are scarce in the Middle East, North Africa and Turkey (MENAT) region, Lancet Global Burden of Disease estimated the prevalence of HF in the MENAT region in 2019 to be 0.78%, versus 0.71% globally. There is also a high incidence of HFpEF risk factors and co-morbidities in the region, including coronary artery disease, diabetes, obesity, hypertension, anaemia and chronic kidney disease. For instance, 14.5-16.2% of adults in the region reportedly have diabetes, versus 7.0% in Europe. Together with increasing life expectancy, this may contribute towards a higher burden of HFpEF in the region than currently reported. This paper aims to describe the epidemiology and burden of HFpEF in the MENAT region, including unique risk factors and co-morbidities. It highlights challenges with diagnosing HFpEF, such as the prioritization of HF with reduced ejection fraction (HFrEF), the specific profile of HFpEF patients in the region and barriers to effective management associated with the healthcare system. Guidance is given on the diagnosis, prevention and management of HFpEF, including the emerging role of sodium-glucose co-transporter-2 inhibitors. Given the high burden of HFpEF coupled with the fact that its prevalence is likely to be underestimated, healthcare professionals need to be alert to its signs and symptoms and to manage patients accordingly. Historically, HFpEF treatments have focused on managing co-morbidities and symptoms, but new agents are now available with proven effects on outcomes in patients with HFpEF.

Estimated plasma volume is not a robust indicator of the severity of congestion in patients with heart failure.

BACKGROUND: Congestion is the main cause of morbidity and a prime determinant of survival in patients with heart failure (HF). However, the assessment of congestion is subjective and estimation of plasma volume (ePV) has been suggested as a more objective measure of congestion. This study aimed to explore the relationships and interactions between ePV, the severity of congestion and survival using a nationwide registry. METHODS: Of the 1054 patients with HF enrolled in the registry, 769 had sufficient data to calculate ePV (using the Duarte, Kaplan, and Hakim equations) and relative plasma volume status (rPVS), and these patients were subsequently included in the present analysis. The severity of congestion was assessed using a 6-point congestion score (CS). Patients were divided into three groups according to the degree of congestion. RESULTS: Out of four equations tested, only ePVDuarte and rPVS were statistically higher in patients with severe congestion as compared to patients with no congestion (p<0.001 for both). Both ePVDuarte (r = 0.197, p<0.001) and rPVS (r = 0.153, p<0.001) showed statistically significant correlations with CS and both had a modest accuracy (70.4% for ePVDuarte and 69.4% for rPVS) to predict a CS ≥3. After a median follow up of 496 days, both ePVDuarte (OR:1.14,95%CI:1.03-1.26, p = 0.01) and rPVS (OR:1.02, 95%CI:1.00-1.03, p = 0.03) were associated with all-cause mortality after adjusting for demographic and clinical variables. However, none of the indices were associated with mortality following the introduction of CS to the models (p>0.05 for both). CONCLUSIONS: Elevated ePVDuarte and rPVS were indicators of congestion but with a limited robustness, and either parameter could be clinically useful when a comprehensive clinical evaluation of congestion is not feasible.

Heart failure and the heart-brain axis.

In heart failure (HF) strong haemodynamic and neuronal signalling feedback interactions between the heart and the central nervous system (CNS) exist that are able to mutually provoke acute or chronic functional impairment. Cerebral injury secondary to HF may include acute stroke, cognitive decline and dementia and depressive disorders. Also brain stem functions are involved in the cardiac-cerebral interaction in HF as neurohormonal control and neuronal reflex circuits are known to be impaired or imbalanced in HF. In turn, impaired cerebral functions may account for direct and indirect myocardial injury and may contribute to symptomatic severity of HF, to disease progression and to increased mortality. Despite the clinical and pathophysiologic significance of the heart-CNS interaction, this relevant field of HF comorbidity is clinically under-recognized with regard to both diagnostic workup and treatment efforts. Here, principal aspects of pathophysiologic heart-CNS interactions related to HF are discussed such as stroke, effects on cognitive function, on depressive disorder and neurovegetative control and neuronal cardiovascular reflex regulation. Aspects of (limited) treatment options for cerebral functional interactions in HF are examined.

Role of lncRNAs in Remodeling of the Coronary Artery Plaques in Patients with Atherosclerosis.

INTRODUCTION: Cardiovascular diseases (CVDs) are the leading cause of death worldwide according to World Health Organization (WHO) data. Atherosclerosis is considered as a chronic inflammatory disease that develops in response to damage to the vascular intima-media layer in most cases. In recent years, epigenetic events have emerged as important players in the development and progression of CVDs. Since noncoding RNA (ncRNAs) are important regulators in the organization of the pathophysiological processes of the cardiovascular system, they have the potential to be used as therapeutic targets, diagnostic and prognostic biomarkers. In this study long noncoding RNA (lncRNA) and mRNA gene expression were compared between coronary atherosclerotic plaques (CAP) and the internal mammary artery (IMA)  which has the same genetic makeup and is exposed to the same environmental stress conditions with CAP in the same individual. METHODS: lncRNA and mRNA gene expressions were determined using the microarray in the samples. Microarray results were validated by RT-qPCR. Differentially expressed genes (DEGs; lncRNAs and mRNAs) were determined by GeneSpring (Ver 3.0) [p values < 0.05 and fold change (FC) > 2]. DAVID bioinformatics program was used for Gene Ontology (GO) annotation and enrichment analyses of statistically significant genes between CAP and IMA tissue. RESULTS AND CONCLUSIONS: In our study, 345 DEGs were found to be statistically significant (p < 0.05; FC > 2) between CAP and IMA. Of these, 65 were lncRNA and 280 were mRNA. Thirty-three lncRNAs were upregulated, while 32 lncRNAs were downregulated. Some of the important mRNAs are SPP1, CYP4B1, CHRDL1, MYOC, and ALKAL2, while some of the lncRNAs are LOC105377123, LINC01857, DIO3OS, LOC101928134, and KCNA3 between CAP and IMA tissue. We also identified genes that correlated with statistically significant lncRNAs. The results of this study are expected to be an important source of data in the development of new genetically based drugs to prevent atherosclerotic plaque. In addition, the data obtained may contribute to the explanation of the epigenetic mechanisms that play a role in the pathological basis of the process that protects the IMA from atherosclerosis.

Acute heart failure and valvular heart disease: A scientific statement of the Heart Failure Association, the Association for Acute CardioVascular Care and the European Association of Percutaneous Cardiovascular Interventions of the European Society of Cardiology.

Acute heart failure (AHF) represents a broad spectrum of disease states, resulting from the interaction between an acute precipitant and a patient's underlying cardiac substrate and comorbidities. Valvular heart disease (VHD) is frequently associated with AHF. AHF may result from several precipitants that add an acute haemodynamic stress superimposed on a chronic valvular lesion or may occur as a consequence of a new significant valvular lesion. Regardless of the mechanism, clinical presentation may vary from acute decompensated heart failure to cardiogenic shock. Assessing the severity of VHD as well as the correlation between VHD severity and symptoms may be difficult in patients with AHF because of the rapid variation in loading conditions, concomitant destabilization of the associated comorbidities and the presence of combined valvular lesions. Evidence-based interventions targeting VHD in settings of AHF have yet to be identified, as patients with severe VHD are often excluded from randomized trials in AHF, so results from these trials do not generalize to those with VHD. Furthermore, there are not rigorously conducted randomized controlled trials in the setting of VHD and AHF, most of the data coming from observational studies. Thus, distinct to chronic settings, current guidelines are very elusive when patients with severe VHD present with AHF, and a clear-cut strategy could not be yet defined. Given the paucity of evidence in this subset of AHF patients, the aim of this scientific statement is to describe the epidemiology, pathophysiology, and overall treatment approach for patients with VHD who present with AHF.

Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology.

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice.

Effect of altitude on ticagrelor-induced dyspnea in patients with acute coronary syndrome.

OBJECTIVE: This study aimed to define the association between altitude and ticagrelor-associated dyspnea in patients with acute coronary syndrome (ACS). METHODS: We studied consecutive patients with de novo ACS who were admitted to two centers at a low altitude (18 and 25 m, n = 65) and two centers at a high altitude (1313 and 1041 m, n = 136). We managed them with ticagrelor between May 2017 and September 2017. Patients with ACS underwent an interventional procedure within <90 minutes in those with ST elevation and within <3 hours in those without ST elevation. We recorded the incidence of dyspnea in patients with ACS receiving ticagrelor therapy. RESULTS: The mean age was 59.5 ± 10 years, and the mean ejection fraction was 43% ± 18%. A total of 110 (56.7%) patients had ST elevation and 84 (43.3%) did not. There were no significant differences in cardiac risk factors, concurrent medications, or procedural variables between the two groups. Dyspnea developed during hospitalization in 53 (38%) patients from high-altitude centers and in 13 (20%) patients from low-altitude centers (66 patients represented 32% of the total ACS cohort). CONCLUSIONS: Dyspnea is a common multifactorial symptom in patients following development of ACS. Ticagrelor-induced dyspnea appears to be associated with altitude.