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    Digoxin is Not Related to Mortality in Patients with Heart Failure: Results from the SELFIE-TR Registry
    (Adis Int Ltd, 2024) Guvenc, Rengin cetin; Guvenc, Tolga Sinan; Caglar, Mert Efe; Al Arfaj, Abdullah Ayar; Behrad, Ailin; Yilmaz, Mehmet Birhan
    AimsDigoxin 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.MethodsA 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.ResultsCrude 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).ConclusionsIn this nationwide cohort, we did not find any evidence for an increased 1-year mortality in heart failure patients on digoxin.
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    The effect of urgent blood pressure reduction on left atrial strain in patients with hypertensive attack Blood pressure lowering affects LA strain
    (Springer, 2023) Asarcikli, Lale Dinc; Can, Fatma; Guvenc, Tolga Sinan; Sert, Sena; Osken, Altug; Dayi, Sennur Unal
    Background: Left atrial (LA) strain is a robust measure of LA function and is a useful parameter to assess left ventricular filling pressure. While initially considered as a load-independent parameter of LA function, later studies have found that acute changes in LA preload may affect LA reservoir and contractile strains. Acute alterations in blood pressure (BP) induces a change in left ventricular (LV) filling pressure without imposing a volume load, thus providing an opportunity to assess the effects of the change in LA afterload on LA mechanics. This study aims to understand the effect of acute BP changes on LA strain. Methods: A total of 40 patients admitted to the emergency department with hypertensive urgency were included. All patients underwent a comprehensive echocardiographic examination including measurement of LA reservoir, conduit and contractile strains. A repeat set of measurements were obtained after BP lowering. Results: Average drop in mean BP following intervention was 18.1 +/- 5.4%. LV end-systolic and end-diastolic volumes, as well as maximum and minimum LA volumes were decreased significantly after BP reduction. The absolute increases in reservoir and contractile strains were 2.3 +/- 4.7% (7.9% +/- 13.8% relative to baseline) and 2.5 +/- 3.3% (13.5 +/- 19.0% relative to baseline), respectively, with both changes being statistically significant (p = 0.003 for reservoir and p < 0.001 for contractile strains). There were no significant changes in conduit strain after BP intervention (p = 0.79). The change in both LA reservoir and contractile strains were more evident in those with a previous diagnosis of hypertension and those with a smaller degree of change in mean BP after intervention. Conclusion: In patients with an acute hypertension, lowering BP leads to an acute improvement in LA reservoir and contractile strains. Thus, acute changes in systemic BP should be considered when LA mechanics are evaluated.
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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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    How to Use Natriuretic Peptides in Patients with Heart Failure with Non-Reduced Ejection Fraction? A Position Paper from the Heart Failure Working Group of Turkish Society of Cardiology
    (Kare Publ, 2023) Celik, Ahmet; Kilicaslan, Baris; Temizhan, Ahmet; Guvenc, Tolga Sinan; Altay, Hakan; Cavusoglu, Yuksel; Yilmaz, Mehmet Birhan
    Natriuretic peptides are widely used in all types of heart failure. Previously, we defined heart failure with non-reduced ejection fraction as patients with heart failure symptoms and/or signs and who have left ventricular ejection fraction > 40%.(1) For the diagnosis of heart failure with preserved ejection fraction, the presence of raised natriuretic peptides is one of the major components of the diagnosis, and raised natriuretic peptides make the diagnosis more likely in patients with heart failure with mildly reduced ejection fraction.(2) The majority of the existing studies have described the utility of natriuretic peptides in patients with heart failure with reduced ejection fraction, but there is not enough data on natriuretic peptides in heart failure patients with heart failure with non-reduced ejection fraction. Despite the insufficient information regarding the usage of natriuretic peptides in heart failure with non-reduced ejection fraction, it is obvious that there is an unmet need to guide how to use natriuretic peptides in these patients. The main goal of this article is to discuss the role of natriuretic peptides in diagnosis, prognosis, and guidance of heart failure treatment in patients with heart failure with non-reduced ejection fraction. The present review discusses the role of natriuretic peptides in heart failure with non-reduced ejection fraction focusing on: the characteristics of natriuretic peptides, primary prevention of heart failure, diagnosis of heart failure with non-reduced ejection fraction in different patient characteristics and comorbidities, prognosis of heart failure, monitoring of heart failure treatment and, how to use in worsening heart failure.
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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.