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    Effect of renal function on the prognostic importance of chloride in patients with heart failure
    (Sage Publications Ltd, 2023) Guvenc, Rengin Cetin; Guevenc, Tolga Sinan; Temizhan, Ahmet; Cavusuglu, Yueksel; Celik, Ahmet; Yilmaz, Mehmet Birhan
    Hypochloremia has recently gained interest as a potential marker of outcomes in patients with heart failure (HF). The exact pathophysiologic mechanism linking hypochloremia to HF is unclear but is thought to be mediated by chloride-sensitive proteins and channels located in kidneys. This analysis aimed to understand whether renal dysfunction (RD) affects the association of hypochloremia with mortality in patients with HF. Using data from a nationwide registry, 438 cases with complete data on serum chloride concentration and 1-year survival were included in the analysis. Patients with an estimated glomerular filtration rate of <60 mL/min/m(2) at baseline were accepted as having RD. Hypochloremia was defined as a chloride concentration <96 mEq/L at baseline. For HF patients without RD at baseline, patients with hypochloremia had a significantly higher 1-year all-cause mortality than those without hypochloremia (41.6% vs 13.0%, log-rank p < 0.001) and the association remained significant after multivariate adjustment (odds ratio (OR): 2.55, 95% confidence interval (CI): 1.25-5.21). The evidence supporting the association was very strong in this subgroup (Bayesian Factor (BF)(10): 48.25, log OR: 1.56, 95% CI: 0.69-2.43). For patients with RD at baseline, there was no statistically significant difference for 1-year mortality for patients with or without hypochloremia (36.3% vs 29.7, log-rank p = 0.35) and there was no evidence to support an association between hypochloremia and mortality (BF10: 1.18, log OR :0.66, 95% CI: -0.02 to 1.35). In patients with HF, the association between low chloride concentration and mortality is limited to those without RD at baseline.
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    Estimated plasma volume is not a robust indicator of the severity of congestion in patients with heart failure
    (Elsevier Science Inc, 2023) Guvenc, Rengin Cetin; Guvenc, Tolga Sinan; Akil, Mehmet Ata; Bekar, Lutfu; Vural, Mustafa Gokhan; Yilmaz, Mehmet Birhan
    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 Hatrim 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 ePV(Duarte) and rPVS were statistically higher in patients with severe congestion as compared to patients with no congestion (p<0.001 for both). Both ePV(Duarte )(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 ePV(Duarte )and 69.4% for rPVS) to predict a CS >= 3. After a median follow up of 496 days, both ePV(Duarte) (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 demo-graphic 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 ePV(Duarte) 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.
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    A Periodic Table approach to understand the pathophysiology of heart failure with preserved ejection fraction
    (Elsevier, 2024) Guvenc, Tolga Sinan; Guvenc, Rengin Cetin; Demir, Gizem; Nikzad, Mohammad Tahir; Ekmekci, Ahmet
    Heart failure with preserved ejection fraction is a complex syndrome that is characterized by symptoms and signs of heart failure without an apparent reduction in left ventricular ejection fraction. Although the main pathophysiologic pathways related to HFpEF are grossly understood, whether all or a specific number of mechanisms are related to the genesis of HFpEF for a given patient remains elusive. Moreover, it has been recently understood that HFpEF is a diverse disease with many phenotypes that have overlapping features, suggesting that a oneway-fits-all approach to understand the pathophysiology of this complex syndrome might not be appropriate. In this manuscript, we introduce a periodic table approach that incorporates both individual pathophysiologic pathways with consequent hemodynamic alterations, in which combinations of such pathophysiologic elements may explain the pathogenetic basis of HFpEF in each phenotype. This approach may held promise for understanding the basis of HFpEF syndrome and may contribute to the personalization of treatment approaches for each individual patient, but further evidence is needed to ascertain whether HFpEF patients have diverse pathogenetic mechanisms as suggested in the periodic table approach.
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    The Relationship Between Epicardial Adipose Tissue and Visceral Adiposity Indexes in Individuals Without Established Atherosclerotic Cardiovascular Disease and Diabetes Mellitus
    (Aves, 2023) Naser, Abdulrahman; Isgandarov, Khagani; Guvenc, Tolga Sinan; Demir, Ibrahim; Kirisci, Murat; Sahin, Muslum; Guvenc, Rengin Cetin
    Objective: Visceral adipose tissue performs an important role in the development of atherosclerotic cardiovascular disease. Expressing its close association with epicardial adipose tissue simplifies the understanding of visceral adipose tissue in terms of atherosclerotic cardiovascular disease risk and facilitates the implementation of necessary lifestyle changes. In this study, we aimed to explore the relationship between epicardial adipose tissue and visceral adipose tissue proxies such as visceral fat rating, visceral adiposity index, and lipid accumulation product index as well as anthropometrics and lipid profile.Methods: This cross-sectional study involved 244 participants (131 female, 113 males), aged 18-83 years without established atherosclerotic cardiovascular disease and diabetes mellitus. Epicardial adipose tissue was measured by transthoracic echocardiography. Visceral fat rating, total body fat percentage, and mass were assessed by a bioimpedance analyzer. Mathematical formulas calculated the visceral adiposity index and lipid accumulation product index. Demographic, clinical, and biochemical information of the participants was provided from the hospital's data system. Homeostasis model assessment of insulin resistance-insulin resistance was calculated using fasting insulin and glucose.Results: Epicardial adipose tissue was significantly correlated with the visceral fat rating, visceral adiposity index, lipid accumulation product index, age, body weight, body mass index, waist circumference, waist-to-height ratio, waist-to-hip ratio, total body fat percentage and mass, systolic blood pressure, diastolic blood pressure, fasting glucose, hemoglobin A1c, insulin, homeostasis model assessment of insulin resistance, total cholesterol, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, and cigarette smoking. Multivariate regression analyses revealed that age (0 = 0.036, P = .001), visceral fat rating (0 = 0.221, P < .001), systolic blood pressure (0 = 0.033, P < .001), diastolic blood pressure (0 = -0.048, P < .001), and cigarette smoking (0 = 0.042, P < .001) were independent variables related to epicardial adipose tissue.Conclusion: Epicardial adipose tissue is associated with cardiovascular disease risk factors and indices of visceral adiposity in people without established atherosclerotic cardiovascular disease and diabetes mellitus.
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    Usefulness of Age, Creatinine and Ejection Fraction- Modification of Diet in Renal Disease Score for Predicting Survival in Patients with Heart Failure
    (Arquivos Brasileiros Cardiologia, 2023) Guvenc, Rengin Cetin; Guvenc, Tolga Sinan; Cavusoglu, Yuksel; Temizhan, Ahmet; Yilmaz, Mehmet Birhan
    Background: While many risk models have been developed to predict prognosis in heart failure (HF), these models are rarely useful for the clinical practitioner as they include multiple variables that might be time-consuming to obtain, they are usually difficult to calculate, and they may suffer from statistical overfitting.Objectives: To investigate whether a simpler model, namely the ACEF-MDRD score, could be used for predicting one-year mortality in HF patients.Methods: 748 cases within the SELFIE-HF registry had complete data to calculate the ACEF-MDRD score. Patients were grouped into tertiles for analyses. For all tests, a p-value <0.05 was accepted as significant.Results: Significantly more patients within the ACEF-MDRD (high) tertile (30.0%) died within one year, as compared to other tertiles (10.8% and 16.1%, respectively, for ACEF-MDRD (low) and ACEF-MDRD (med) , p<0.001 for both comparisons). There was a stepwise decrease in one-year survival as the ACEF-MDRD score increased (log-rank p<0.001). ACEF-MDRD was an independent predictor of survival after adjusting for other variables (OR: 1.14, 95%CI:1.04 - 1.24, p=0.006). ACEF-MDRD score offered similar accuracy to the GWTG-HF score for predicting one-year mortality (p=0.14).Conclusions: ACEF-MDRD is a predictor of mortality in patients with HF, and its usefulness is comparable to similar yet more complicated models.