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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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    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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    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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    Thrombolysis in myocardial infarction risk index predicts one-year mortality in patients with heart failure: an analysis of the SELFIE-TR study
    (KARGER, 2022) Güvenç, Rengin Çetin; Güvenç, Tolga Sinan; Ural, Dilek; Cavusoglu, Yuksel; Yilmaz, Mehmet Birhan
    Objective: Predicting outcomes is an essential part of evaluation in 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 understand predictive usefulness of Thrombosis in Myocardial Infarction Risk Index (TIMI-RI), a simple index that is calculated at bedside using three commonly available variables, using data from a multicenter HF registry. Subjects and Methods: A total of 728 patients from 23 centers were included to this analysis. Data on hospitalizations and mortality were collected by direct interviews, phone calls and electronic databases. TIMI-RI was calculated as defined before. 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 were dead within one-year follow up as compared to 14.5% of patients within the 1st tertile and 15.6% patients within the 2nd tertile (p<0.001, log-rank p<0.001 for pairwise comparisons on survival analysis). 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 one-year mortality. This predictive usefulness was independent of other demographic, examination and clinical variables (OR:1.74, 95%CI:1.05-2.86, p=0.036). Conclusion: TIMI-RI is a simple index that predicts one-year mortality in patients with HF, and it could be useful for rapid evaluation and triage of HF patients at the time of initial contact.
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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.