Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients.

Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.

Evaluation of pulmonary arterial stiffness and comparison with right ventricular functions in patients with cirrhosis preparing for liver transplantation.

OBJECTIVE: Pulmonary complications are common in patients with liver cirrhosis. Devolopment of pulmonary hypertension (PH) is associated with a poor prognosis in these patients. Pulmonary arterial stiffness (PAS) is considered an early sign of pulmonary vascular remodeling. The aim of this study is to investigate PAS and compare it with right ventricular (RV) functions in patients with cirrhosis who are scheduled for liver transplantation. METHODS: The study included 52 cirrhosis patients (mean age 51.01 ± 12.18 years, male gender 76.9%) who were prepared for liver transplantation and 59 age and sex matched (mean age 51.28 ± 13.63 years, male gender 62.7%) healthy individuals. Patients with left ventricular ejection fraction (LVEF) less than 55%, ischemic heart disease, more than mild valvular heart disease, chronic pulmonary disease, congenital heart disease, rheumatic disease, moderate to high echocardiographic PH probability, rhythm or conduction disorders on electrocardiography were excluded from the study. In addition to conventional echocardiographic parameters, PAS value, pulmonary vascular resistance (PVR) and RV ejection efficiency was calculated by the related formulas with transthoracic echocardiography (TTE). RESULTS: Demographic characteristics and cardiovascular risk factors of the groups were similar. PAS, PVR, and sPAP values were found to be significantly higher in the patient group (20.52 ± 6.52 and 13.73 ± 2.05; 1.43 ± 0.15 and 1.27 ± 0.14; 27.69 ± 3.91 and 23.37 ± 3.81 p < 0.001, respectively). RV FAC and RV Ee were significantly lower and RV MPI was significantly higher in the patient group (45.31 ± 3.85 and 49.66 ± 3.62, p < 0.001; 1.69 ± 0.35 and 1.85 ± 0.23, p = 0.005; 0.39 ± 0.07 and 0.33 ± 0.09, p = 0.001, respectively). PAS was significantly correlated with RV FAC and MPI (r = -0.423, p < 0.001; r = 0.301, p = 0.001, respectively). CONCLUSIONS: Increased PAS in cirrhosis patients may be associated with early pulmonary vascular involvement. Evaluation of RV functions is important to determine the prognosis in these patients. FAC, MPI, and RV Ee measurements instead of TAPSE or RV S' may be more useful in demonstrating subclinical dysfunction. The correlation of PAS with RV FAC and MPI may indicate that RV subclinical dysfunction is associated with early pulmonary vascular remodeling in patients with liver cirrhosis.

Thrombolysis in Myocardial Infarction Risk Index Predicts 1-Year Mortality in Patients with Heart Failure: An Analysis of the SELFIE-TR Study.

OBJECTIVE: Predicting outcomes is an essential part of evaluation of patients with heart failure (HF). While there are multiple individual laboratory and imaging variables as well as risk scores available for this purpose, they are seldom useful during the initial evaluation. In this analysis, we aimed to elucidate the predictive usefulness of Thrombolysis in Myocardial Infarction Risk Index (TIMI-RI), a simple index calculated at the bedside with three commonly available variables, using data from a multicenter HF registry. SUBJECTS AND METHODS: A total of 728 patients from 23 centers were included in this analysis. Data on hospitalizations and mortality were collected by direct interviews, phone calls, and electronic databases. TIMI-RI was calculated as heart rate × (age/10)2/systolic pressure. Patients were divided into three equal tertiles to perform analyses. RESULTS: Rehospitalization for HF was significantly higher in patients within the 3rd tertile, and 33.5% of patients within the 3rd tertile had died within 1-year follow-up as compared to 14.5% of patients within the 1st tertile and 15.6% of patients within the 2nd tertile (p < 0.001, log-rank p < 0.001 for pairwise comparisons). The association between TIMI-RI and mortality remained significant (OR: 1.74, 95% CI: 1.05-2.86, p = 0.036) after adjustment for other variables. A TIMI-RI higher than 33 had a negative predictive value of 84.8% and a positive predictive value of 33.8% for prediction of 1-year mortality. CONCLUSION: TIMI-RI is a simple index that predicts 1-year mortality in patients with HF; it could be useful for rapid evaluation and triage of HF patients at the time of initial contact.

Effects of iron deficiency on left ventricular functions in young women regardless of anemia: A speckle tracking echocardiography study.

BACKGROUND: Iron deficiency is one of the most common metabolic disorders worldwide and affects multiple organs and systems including the cardiovascular (CV) system. Iron deficiency can cause structural and functional changes in the myocardium. The aim of the study is to evaluate left ventricular (LV) functions in patients with low ferritin levels without anemia by two-dimensional "speckle tracking" echocardiography (2D STE). METHODS: We studied 90 participants (all female) that were divided into two groups according to ferritin levels (49 patients with ferritin levels <30 ng/mL, 41 age-matched controls with >30 ng/mL). Patients with anemia (hemoglobin level <12 g/dL), known CV disease, diabetes mellitus, low ejection fraction (<55%), active infection, high ferritin levels (>200 ng/mL) were excluded. All patients were evaluated by transthoracic echocardiography. In addition to conventional echocardiographic parameters and Doppler measurements, LV global longitudinal strain (GLS) and strain rate (GLSR) were obtained by 2D STE. RESULTS: Mean ferritin level was 18.96 ± 7.29 ng/mL in low ferritin group, and was 61.22 ± 26.14 ng/mL in control group. There were no significant differences according to conventional and Doppler echocardiographic parameters between the groups. LV GLS and GLSR values were significantly lower in low ferritin group comparing with control group (17.31% ± 1.56 and 18.96% ± 1.53, p < 0.001; 0.64 ± 0.13 1/s and 0.81 ± 0.13 1/s, p < 0.001, respectively). There was a significant positive correlation between ferritin levels and LV GLS and GLSR values in study group (r = 0.482, p < 0.001; r = 0.387, p < 0.001, respectively). Ferritin level was also detected as an independent risk factor for GLS value < -18% in logistic regression analysis. In ROC curve analysis, the area under the curve for predicting GLS < -18% was 0.801 (p < 0.001, 95% CI 0.70-0.89) and the threshold of ferritin value was 28.5 ng/mL (sensitivity 76.1%, specificity 77.3%). DISCUSSION: Low ferritin levels can cause subclinical LV systolic dysfunction in patients without anemia. STE provides detailed information about LV functions. With larger studies, these patients should be followed more closely and considered for iron replacement treatment before developing anemia.

Authorship: from credit to accountability. Reflections from the Editors' Network.

The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

Evaluation of serum sST2 and sCD40L values in patients with microvascular angina.

OBJECTIVES: Coronary microvascular dysfunction plays a major role in the pathogenesis of microvascular angina (MVA). Along with endothelial dysfunction, microvascular atherosclerosis and inflammation seem to contribute to the development of coronary microvascular dysfunction. Serum soluble ST2 (sST2) and serum soluble CD40 ligand (sCD40L) are two biomarkers associated with inflammation and atherosclerosis. The aim of this study was to investigate the role of these biomarkers in the pathogenesis of MVA and determine their possible association with coronary microvascular dysfunction. METHODS: A total of 152 patients were included in the study. Ninety-one patients with MVA {median age 56 years (40-79), of which 55 are women} and sixty-one controls {median age 52 (38-76), of which 29 are women} were included in the study. Serum concentration of sST2 and sCD40L were measured with a commercially available ELISA kit. RESULTS: Serum sST2 (median 13.6 ng/ml; interquartile range (IQR), 3.5-63.8 ng/ml vs median 10.6 ng/ml; IQR, 2.9-34.2 ng/ml, p < 0.0005) and sCD40L (median 5.3 ng/ml; IQR, 0.5-20.6 ng/ml vs median 2.2 ng/ml; IQR, 0.7-10.8 ng/ml, p < 0.0005) were significantly higher in patients with MVA compared to controls. Analysis of the associations between these biomarkers and potential contributors of MVA revealed that serum sST2 showed a positive correlation with LDL-cholesterol (r = 0.19, p = 0.016) and serum sCD40L concentrations correlated positively with hs-CRP (r = 0.22, p = 0.005). In logistic regression analysis, sCD40L and hs-CRP but not sST2 were found to be significantly associated with MVA. CONCLUSION: Higher serum concentrations of sST2 and sCD40L in MVA patients may be associated with inflammatory activation and coronary microvascular dysfunction. Larger studies are required for understanding their role in the pathogenesis of inflammatory and possibly fibrotic process in MVA patients.

A simple discharge risk model for predicting 1-year mortality in hospitalised acute decompansated heart failure patients with reduced ejection fraction.

OBJECTIVE: The risk stratification for prognosis in heart failure is very important for optimal disease management and decision making. The aim of this study was to establish a simple discharge 1-year mortality prediction model by integrating data obtained from demographic characteristics, clinical evaluation, laboratory biomarkers and echocardiographic evaluation of hospitalised heart failure with reduced ejection fraction (HFrEF) patients with acute decompensation. METHODS AND RESULTS: A risk score model was developed based on ß-coefficient number of variables in a multivariable logistic regression model which was created with the use of data on clinical, laboratory, imaging and therapeutic findings of 670 patients (65.4% males, 65 ± 11 years) who was hospitalised with acute decompensated HFrEF. The mean left ventricular ejection fraction (LVEF) was 26 ± 9%. Independent predictors of mortality were: age ≥75 years, sodium <130 mEq/L, hepatomegaly at admission, unable to use beta-blocker at discharge and LVEF ≤20%. The 1-year mortality rate was 7.8% in the study population. The existence of each predictor was scored as 1 point and the discharge risk score identified patients into low (0-1 points), intermediate (2-3 points) and high (4-5 points) risk individuals with 3, 15.6 and 44.4% 1-year mortality rates, respectively. The model performance evaluated by concordance index was 0.74. CONCLUSIONS: This simple discharge risk score model for hospitalised acute decompensated HFrEF patients using easily determined demographic characteristics, clinical signs, echocardiographic and laboratory data is a valuable and an easy risk assessment tool to use at point-of-care.

Effect of Oral Nitrates on All-Cause Mortality and Hospitalization in Heart Failure Patients with Reduced Ejection Fraction: A Propensity-Matched Analysis.

BACKGROUND: Hydralazine-nitrate combination is recommended for patients with heart failure with reduced ejection fraction (HFrEF)/systolic heart failure who are symptomatic despite guideline-directed medical therapy (GDMT). Use of nitrates alone for this indication is not well-established. This study aims to evaluate the effect of oral nitrates on all-cause mortality and hospitalization in HFrEF patients using GDMT. METHODS AND RESULTS: Nitrate prescription at discharge and its association with all-cause mortality and heart failure hospitalization were examined in a propensity-matched analysis of 648 HFrEF patients followed for a median of 56 months. A total of 269 (42%) patients died during that period. In Cox regression analysis, nitrate usage was associated with a slightly increased mortality risk compared with not using nitrates (hazard ratio 1.29; 95% confidence interval 1.01-1.65; P = .040), which continued modestly after the propensity-matched analysis (hazard ratio 1.26; 95% confidence interval 0.95-1.68; P = .102). In both prematch and propensity-matched analyses, nitrate use was not associated with risk of rehospitalization. No significant effect was detected on subgroups stratified by coronary artery disease, age, gender, and background medical therapy. CONCLUSIONS: In this study, oral nitrate use alone in addition to GDMT did not affect all-cause mortality and hospitalization risk in HFrEF patients during a long-term follow-up. There was even a modest tendency for increased risk of mortality.

Early Thrombosuction and Tirofiban Use in Knee and Below-Knee Arterial Thrombosis.

BACKGROUND Acute limb ischemia (ALI) is a clinical entity with a high rate of morbidity and mortality. Despite advances and variety of its management, there is still no criterion standard treatment. The goal of this study was to evaluate the effect of tirofiban use on the early and 6-month prognosis of patients with knee and below-knee arterial thrombosis who were treated with percutaneous thrombosuction (PT) within 24 h. MATERIAL AND METHODS Data of consecutive ALI patients who were diagnosed with popliteal and infra-popliteal arterial thrombosis and underwent PT procedure within 24 h between January 2010 and September 2015 were evaluated retrospectively. Patients were separated into 2 groups according to tirofiban usage. RESULTS A total of 105 patients (mean age 67±16; 53% men) were included in the study. Atrial fibrillation (n 64, 61%) and hypertension (n 60, 57%) were the most frequent comorbidities in patients with thromboembolic events. A significantly higher rate of distal embolization (6% vs. 16%; p=0.01) and slow-flow (17% vs. 30%; p<0.01) developed in patients who were not treated with tirofiban after the PT procedure. Although major and minor bleeding were more frequent in the tirofiban group, only the rate minor bleeding was statistically significant (29% vs. 9%, p=0.001). Reverse embolic event ratio was similar in both groups. Although there was a higher rate of amputation in patients not treated with tirofiban, the difference was not significant. CONCLUSIONS Adding tirofiban to PT reduces angiographic thromboembolic complications. Usage of tirofiban in patients prone to thromboembolic events may be useful for improving success of the PT procedure, with a reasonable bleeding ratio.

Predictors of Long-Term Mortality and Frequent Re-Hospitalization in Patients with Acute Decompensated Heart Failure and Kidney Dysfunction Treated with Renin-Angiotensin System Blockers.

BACKGROUND Assessment of risk for all-cause mortality and re-hospitalization is an important task during discharge of acute heart failure (AHF) patients, as they warrant different management strategies. Treatment with optimal medical therapy may change predictors for these 2 end-points in AHF patients with renal dysfunction. The aim of this study was to evaluate the predictors for long-term outcome in AHF patients with kidney dysfunction who were discharged on optimal medical therapy. MATERIAL AND METHODS The study was conducted retrospectively. The study group consisted of 225 AHF patients with moderate-to-severe kidney dysfunction, who were hospitalized at Kocaeli University Hospital Cardiology Clinic and who were prescribed beta-blockers and ACE-inhibitors or angiotensin II receptor blockers at discharge. Clinical, echocardiographic, and biochemical predictors of the composite of total mortality and frequent re-hospitalization (≥3 hospitalizations during the follow-up) were assessed using Cox regression and the predictors for each end-point were assessed by competing risk regression analysis. RESULTS Incidence of all-cause mortality was 45.3% and frequent readmissions were 49.8% in a median follow-up of 54 months. The associates of the composite end-point were age, NYHA class, respiration rate on admission, eGFR, hypoalbuminemia, mitral valve E/E' ratio, and ejection fraction. In competing risk regression analysis, right-sided HF, hypoalbuminemia, age, and uric acid appeared as independent associates of all-cause mortality, whereas NYHA class, NT-proBNP, mitral valve E/E' ratio, and uric acid were predictors for re-hospitalization. CONCLUSIONS Predictors for all-cause mortality in AHF with kidney dysfunction treated with optimal therapy are mainly related to advanced HF with right-sided dysfunction, whereas frequent re-hospitalization is associated with volume overload manifested by increased mitral E/E' ratio and NT-proBNP levels.

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors' Network.

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship- emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors' Network of the European Society of Cardiology.

Associations Between Neutrophil Gelatinase Associated Lipocalin, Neutrophil-to-Lymphocyte Ratio, Atrial Fibrillation and Renal Dysfunction in Chronic Heart Failure.

BACKGROUND Atrial fibrillation (AF) and renal dysfunction are two common comorbidities in patients with chronic heart failure with reduced ejection fraction (HFrEF). This study evaluated the effect of permanent AF on renal function in HFrEF and investigated the associations of atrial fibrillation, neutrophil gelatinase-associated lipocalin (NGAL), and neutrophil-to-lymphocyte ratio (NLR) with adverse clinical outcome. MATERIAL AND METHODS Serum NGAL levels measured by ELISA and NLR were compared between patients with sinus rhythm (HFrEF-SR, n=68), with permanent AF (HFrEF-AF, n=62), and a healthy control group (n=50). RESULTS Mean eGFR levels were significantly lower, and NLR and NGAL levels were significantly higher in the HFrEF patients than in the control patients but the difference between HFrEF-SR and HFrEF-AF was not statistically significant (NGAL: 95 ng/mL in HFrEF-SR, 113 ng/mL in HFrEF-AF and 84 ng/mL in the control group; p<0.001). Independent associates of baseline eGFR were age, hemoglobin, NLR, triiodothyronine, and pulmonary artery systolic pressure. In a mean 16 months follow-up, adverse clinical outcome defined as progression of kidney dysfunction and composite of all-cause mortality and re-hospitalization were not different between HFrEF-SR and HFrEF-AF patients. Although NGAL was associated with clinical endpoints in the univariate analysis, Cox regression analysis showed that independent predictors of increased events were the presence of signs right heart failure, C-reactive protein, NLR, triiodothyronine, and hemoglobin. In ROC analysis, a NLR >3 had a 68% sensitivity and 75% specificity to predict progression of kidney disease (AUC=0.72, 95% CI 0.58-0.85, p=0.001). CONCLUSIONS Presence of AF in patients with HFrEF was not an independent contributor of adverse clinical outcome (i.e., all-cause death, re-hospitalization) or progression of renal dysfunction. Renal dysfunction in HFrEF was associated with both NLR and NGAL levels, but systemic inflammation reflected by NLR seemed to be a more important determinant of progression of kidney dysfunction.

Association between resolution of fragmented QRS and response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been recommended for patients with symptomatic heart failure and a wide QRS. Fragmented QRS (fQRS) on a 12-lead electrocardiography (ECG) has been shown to predict cardiac events. We aimed to investigate the relationship between resolution of fQRS and response to CRT. METHODS: Sixty-seven consecutive patients (38 men, mean age 65 ± 11) with left bundle branch block and fQRS on ECG undergoing CRT were studied. The presence of fQRS was assessed using standardized criteria. Echocardiographic response to CRT was defined by a ≥15% reduction in left ventricular end-systolic volume (LVESV) and resolution of fQRS was defined as decrease in number of leads with fQRS on ECG at 6 months follow-up. RESULTS: Thirty-nine patients (58%) had response to CRT. LVESV significantly decreased from 150 ± 64 to 100 ± 48 in responders (P = 0.001). There was not any significant decrease in nonresponders (LVESV; from 157 ± 70 to 153 ± 66, P = 0.45). The number of leads with fQRS was decreased from 4.4 ± 1.8 to 1.7 ± 1.6 in responder patients (P < 0.001). The number of leads with fQRS was not significantly changed in nonresponders. (4.2 ± 2.2 vs. 5.1 ± 2.4, P = 0.06). In multivariate analysis, significant associates of response to CRT was evaluated adjusting for etiology of cardiomyopathy, baseline QRS width, left ventricular ejection fraction, number of leads with fQRS and resolution of fQRS. Resolution of fQRS was the only predictor of response to CRT (OR 0.018, 95% CI, 0.004-0.083, P < 0.001). CONCLUSIONS: After adjusting for potential confounders, resolution of fQRS, is associated with response to CRT.

Discharge risk scoring method for predicting mortality in hospitalized chronic heart failure patients with severe systolic dysfunction.

OBJECTIVE: Prognostic risk stratification in heart failure is crucial to guide clinical decision-making.The aim of our study was to develop a prognostic discharge risk score model to predict all-cause mortality for chronic heart failure patients with multiple co-morbidities and severe systolic dysfunction. METHODS AND RESULTS: A multivariable logistic regression model was developed with the use of data on clinical, laboratory, imaging and therapeutic findings of 630 patients with advanced systolic heart failure. A risk score model was developed based on multiplying the beta-coefficient number of each variable in the multivariable model. The model performance was evaluated by concordance index and internally validated by the bootstrapping method. 313 patients (49.7%) of the cohort died during a median follow-up duration of 54 months. Median age was 66 years, 37% were female, 26% had atrial fibrillation and 40% had diabetes mellitus. The mean left ventricular ejection fraction (EF) was 25 +/- 10% and 264 patients (42%) had left ventricular EF < or = 20%. Independent predictors of mortality were older than 70 years, orthopnoea, previous hospitalisations, lack of renin-angiotensin system inhibitor therapy at discharge, hyperuricaemia (>7 mg/dl) and haemoglobin level (<10 g/dL). Discharge risk score identified low-, intermediate- and high-risk individuals with 18%, 40% and 52% mortality rates, respectively. The risk score had a discrimination ability with a concordance index of 0.70. CONCLUSIONS: In a large heart failure cohort, including patients with severe systolic dysfunction and having multiple comorbidities, a simple discharge risk score with non-invasive and easy-to-obtain variables during hospital admission represents a valuable tool for risk assessment.

Major depressive disorder in chronic heart failure patients: Does silent cerebral infarction cause major depressive disorder in this patient population?

OBJECTIVE: Depression frequently occurs in patients with heart failure as similar pathophysiological mechanisms present in both these diseases. Patients with dilated cardiomyopathy (DCM) have a high incidence of clinically asymptomatic silent cerebral infarction (SCI). This study aimed to evaluate the relation between SCI and major depressive disorder (MDD), and between MDD and clinical and biochemical parameters in DCM patients. METHODS: Patients with ischemic and non-ischemic DCM who had chronic heart failure (CHF) (39 male, 10 female, age 60±10 years) were included in the study. Mean patient ejection fraction (EF) was 34±10%. Patients had no localized neurological symptoms or stroke history. The etiology of DCM was ischemic in 40 and non-ischemic in 9 patients. Twenty-five age-matched healthy volunteers served as a control group for comparison of SCI and MDD prevalence. RESULTS: Patients had mild to severe CHF symptoms. Prevalence of SCI and MDD was significantly higher in patients with DCM than in the control group; 63% vs 8%; p<0.001, and 52% vs 20%; p<0.001 respectively. Patients with SCI had a higher prevalence of MDD than patients without SCI in DCM (61% vs 27%, p=0.02). CONCLUSION: CHF patients have an increased prevalence of SCI and MDD. Patients with SCI have a higher prevalence of MDD compared to patients without SCI in CHF.

Lymphocytopenia is associated with poor NYHA functional class in chronic heart failure patients with reduced ejection fraction.

OBJECTIVE: In heart failure (HF) patients, functional capacity has been demonstrated to be a marker of poor prognosis, independent of left ventricular ejection fraction (EF). Lymphocyte count is currently recognized in certain risk stratification scores for chronic HF, and severe HF is associated with lymphocytopenia. However, no data exists on the association between lymphocyte count and functional capacity in patients with stable HF. This study aimed to assess the relationship between lymphocyte count and New York Heart Association (NYHA) functional capacity in systolic HF outpatients. METHODS: The Turkish Research Team-HF (TREAT-HF) is a network which undertakes multi-center observational studies in HF. Data on 392 HF reduced ejection fraction (HFREF) patients from 8 HF centers are presented here. The patients were divided into two groups and compared: Group 1 comprised stable HFREF patients with mild symptoms (NYHA Class I-II), while Group 2 consisted of patients with NYHA Class III-IV symptoms. RESULTS: Patient mean age was 60±14 years. Lymphocyte count was lower in patients with NYHA functional classes III and IV than in patients with NYHA functional classes I and II, (0.9 [0.6-1.5]x1000 versus 1.5 [0.7-2.2]x1000, p<0.001). In multivariate logistic regression analysis, lymphocyte count (OR: 0.602, 95% CI: 0.375-0.967, p=0.036), advanced age, male gender, presence of hypertension, EF, left atrium size, systolic pulmonary artery pressure, neutrophil and basophil counts, creatinine level, and diuretic usage were associated with poor NYHA functional class in systolic HF outpatients. CONCLUSION: The present study demonstrated that in stable HFREF outpatients, lymphocytopenia was strongly associated with poor NYHA function, independent of coronary heart disease risk factors.

What is the lowest value of left ventricular baseline ejection fraction that predicts response to cardiac resynchronization therapy?

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with refractory heart failure. However, many patients do not respond to therapy. Although it has been thought that there was no relation between response to CRT and baseline ejection fraction (EF), the response rate of patients with different baseline LVEF to CRT has not been evaluated in severe left ventricular systolic dysfunction. We aimed to investigate any difference in response to CRT between the severe heart failure patients with different baseline LVEF. MATERIAL AND METHODS: In this study, 141 consecutive patients (mean age 59±13 years; 89 men) with severe heart failure and complete LBBB were included. Patients were divided into 3 groups according to their baseline LVEF: 5-15%, Group 1; 15-25%, Group 2, and 25-35%, Group 3. NYHA functional class, LVEF, LV volumes, and diameters were assessed at baseline and after 6 months of CRT. A response to CRT was defined as a decrease in LVSVi (left ventricular end-systolic volume index) ≥10% on echocardiography at 6 months. RESULTS: After 6 months, a significant increase of EF and a significant decrease of LVESVi and LVEDVi after 6 months of CRT were observed in all groups. Although the magnitude of improvement in EF was biggest in the first group, the percentage of decrease in LVESVi and LVEDVi was similar between the groups. The improvement in NYHA functional class was similar in all EF subgroups. At 6-month follow-up, 100 (71%) patients showed a reduction of >10% in LVESVi (mean reduction: -15.5±26.1 ml/m^2) and were therefore classified as responders to CRT. Response rate to CRT was similar in all groups. It was 67%, 75%, and 70% in Group 1, 2, and 3, respectively, at 6-month follow-up (p>0.05). There was no statistically significant relation between the response rate to CRT and baseline LVEF, showing that the CRT has beneficial effects even in patients with very low LVEF. CONCLUSIONS: It seems there is no lower limit for baseline LVEF to predict non-response to CRT in eligible patients according to current guidelines.

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.

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.