José M. Andreu-Cayuelas

Serial Monitoring of Soluble Interleukin Family Member ST2 in Patients with Acutely Decompensated Heart Failure

Objectives: To determine whether serial measures of the interleukin receptor family member soluble ST2 (sST2) provide additional prognostic information to baseline measures for long-term risk stratification of acutely decompensated heart failure (ADHF) patients. Methods: We prospectively enrolled 72 ADHF patients. Blood samples were collected to measure sST2 concentrations at presentation and on day 4 of hospitalization. All patients were clinically followed, and vital status was registered. Results: Between presentation and day 4, sST2 concentrations decreased from 62 ng/ml (interquartile range 38–105) to 44 ng/ml (interquartile range 26–72; p < 0.001). Both sST2 concentrations at presentation [hazard ratio (HR) 1.011, 95% confidence interval (CI) 1.005–1.016; p < 0.001] and on day 4 (HR 1.015, 95% CI 1.005–1.024; p = 0.003) were independent predictors of mortality. Patients with sST2 ≤76 ng/ml at presentation and ≤46 ng/ml on day 4 had the lowest mortality rates (3%), whereas those with both sST2 values above these cutoff points had the highest mortality (50%). C index and reclassification analyses demonstrated that the use of serial sST2 measures resulted in an improvement in the accuracy of mortality prediction. Conclusions: Among ADHF patients, sST2 concentrations tend to decrease following initiation of treatment and are prognostic both at presentation and during hospitalization. Serial sampling of sST2 adds prognostic information and may provide a basis for enhanced clinical decision making.

Comparison of estimated glomerular filtration rate equations for dosing new oral anticoagulants in patients with atrial fibrillation

INTRODUCTION AND OBJECTIVES New oral anticoagulants require dosing adjustment according to renal function. We aimed to determine discordance in hypothetical recommended dosing of these drugs using different estimated glomerular filtration rate equations in patients with atrial fibrillation. METHODS Cross-sectional analysis of 910 patients with atrial fibrillation and an indication for oral anticoagulation. The glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations. For dabigatran, rivaroxaban, and apixaban we identified dose discordance when there was disagreement in the recommended dose based on different equations. RESULTS Among the overall population, relative to Cockcroft-Gault, discordance in dabigatran dosage was 11.4% for Modification of Diet in Renal Disease and 10% for Chronic Kidney Disease Epidemiology Collaboration, discordance in rivaroxaban dosage was 10% for Modification of Diet in Renal Disease and 8.5% for the Chronic Kidney Disease Epidemiology Collaboration. The lowest discordance was observed for apixaban: 1.4% for Modification of Diet in Renal Disease and 1.5% for the Chronic Kidney Disease Epidemiology Collaboration. In patients with Cockcroft-Gault<60mL/min or elderly patients, discordances in dabigatran and rivaroxaban dosages were higher, ranging from 13.2% to 30.4%. Discordance in apixaban dosage remained<5% in these patients. CONCLUSIONS Discordance in new oral anticoagulation dosages using different equations is frequent, especially among elderly patients with renal impairment. This discordance was higher in dabigatran and rivaroxaban dosages than in apixaban dosages. Further studies are needed to clarify the clinical importance of these discordances and the optimal anticoagulant dosages depending on the use of different equations to estimate renal function.

Impact of Variations in Kidney Function on Nonvitamin K Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Recent Acute Heart Failure.

INTRODUCTION AND OBJECTIVES Renal impairment and fluctuations in renal function are common in patients recently hospitalized for acute heart failure and in those with atrial fibrillation. The aim of the present study was to evaluate the hypothetical need for dosage adjustment (based on fluctuations in kidney function) of dabigatran, rivaroxaban and apixaban during the first 6 months after hospital discharge in patients with concomitant atrial fibrillation and heart failure. METHODS An observational study was conducted in 162 patients with nonvalvular atrial fibrillation after hospitalization for acute decompensated heart failure who underwent creatinine determinations during follow-up. The hypothetical recommended dosage of dabigatran, rivaroxaban and apixaban according to renal function was determined at discharge. Variations in serum creatinine and creatinine clearance and consequent changes in the recommended dosage of these drugs were identified during 6 months of follow-up. RESULTS Among the overall study population, 44% of patients would have needed dabigatran dosage adjustment during follow-up, 35% would have needed rivaroxaban adjustment, and 29% would have needed apixaban dosage adjustment. A higher proportion of patients with creatinine clearance < 60 mL/min or with advanced age (≥ 75 years) would have needed dosage adjustment during follow-up. CONCLUSIONS The need for dosage adjustment of nonvitamin K oral anticoagulants during follow-up is frequent in patients with atrial fibrillation after acute decompensated heart failure, especially among older patients and those with renal impairment. Further studies are needed to clarify the clinical importance of these needs for drug dosing adjustment and the ideal renal function monitoring regime in heart failure and other subgroups of patients with atrial fibrillation.

Methods of kidney function assessment in non-valvular atrial fibrillation in the era of new oral anticoagulants

We have readwith great interest the letter by Jolobe OM concerning the importance of kidney function assessment for new oral anticoagulant (NOAC) dosing adjustment [1]. However, we think that there is a lack of consensus on which method should be used for this purpose. Given that the use of different equations frequently result in discordances in estimated glomerular filtration rate (GFR), and consequently in NOAC recommended doses [2,3], we consider that the evaluation of methods that are used for renal function assessment before prescribing NOAC in daily practice could be of clinical interest. In this study, we performed a cross-sectional study based on a survey of Spanish physicians from 17 hospitals and 8 primary care centers. The study population consisted of 642 physicians who participated voluntarily and anonymously. Of them, 489 (76.2%) declared to have previously used NOAC. Among these subjects, there was only one (0.2%) who does not estimate renal function before prescribing NOAC. Fig. 1 shows the different methods of renal function assessment used. The Modification of Diet in Renal Disease Study (MDRD) and Cockcroft–Gault (CG) equations were the most frequently used: 46.6% (n = 228) and 39.1% (n = 191) respectively, while the 24-hour urine creatinine excretion and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) were the less used for this purpose: 3.3% (n = 16) and 1.0% (n = 5) respectively. The results of the present study show that there is a high variability in the methods used for renal function assessment before prescribing NOAC. This variability may be explained in part by the lack of consensus onwhat should be themethodused for this purpose. In fact, theU.S. FDA (Food and Drug Administration) and NKDEP (National Kidney Disease Education Program) suggest that both CG and MDRD equations could be used interchangeably for drug dosing adjustment [4,5], while the European Medicines Agency (EMA) recommends the use of CG equation because phase III clinical trials evaluating NOAC have used this equation [6–8]. Compared to randomized clinical trials setting, we found that MDRD is the most frequently method used for NOAC dosing

TWEAK and NT-proBNP levels predict exercise capacity in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate hypertrophy, myocyte disarray and increased interstitial fibrosis. The tumour necrosis factor‐like weak inducer of apoptosis (TWEAK) is a cell surface cytokine with biological activities including stimulation of cell growth, induction of inflammatory cytokines and stimulation of apoptosis. There are controversial data about the potential role of TWEAK in different cardiovascular pathologies. NT‐proBNP is an established biomarker of myocardial wall stress, associated with poor functional class in HCM. We hypothesized that effort capacity in patients with HCM could be related to serum levels of these biomarkers.

SAMe-TT2R2 Score: Useful in All Patients With Nonvalvular Atrial Fibrillation? Response

We appreciate the comments of Escobar et al regarding our article. The introduction of alternatives to vitamin K antagonists (VKA) has demonstrated the importance of the early identification of patients who are most likely to exhibit poor International Normalized Ratio (INR) control. The SAMe-TT2R2 score has been proposed as a predictor of poor anticoagulation control. Although it has been validated in a number of populations of patients with atrial fibrillation, this score could still be improved, as the C-statistic reported in these studies is low (0.550.6). Moreover, our results indicate that it is less useful in patients in unstable situations, such as recent decompensated heart failure. Factors such as a history of bleeding, multidrug therapy, and eating habits appear to show promise in terms of improving the predictive capacity of new scores that will better distinguish those patients who are less suitable to receive VKA. Other factors—such as abuse of alcohol or other drugs, chronic kidney disease, cancer, mental disorders, and even the experience of the physician adjusting the VKA dose—have also been shown to be capable of predicting an inadequate percentage of time in therapeutic range. However, although new scoring systems will probably enhance our capacity to predict poor INR control, they should not involve a degree of complexity that would limit their use in routine clinical practice, unless they offer a significant improvement.

SAMe-TT2R2 Score Does Not Predict Time in Therapeutic Range in Atrial Fibrillation Patients After Hospitalization for Acute Decompensated Heart Failure

Feasibility of the Engager aortic transcatheter valve system using a flexible overthe-wire design. Eur J Cardiothorac Surg. 2012;42:e48–52. 5. Sündermann SH, Holzhey D, Bleiziffer S, Treede H, Falk V. Medtronic Engager bioprosthesis for transapical transcatheter aortic valve implantation. EuroIntervention. 2013;9:S97–100. 6. Sundermann SH, Grünenfelder J, Corti R, Rastan AJ, Linke A, Lange R, et al. Outcome of patients treated with Engager transapical aortic valve implantation: One-year results of the feasibility study. Innovations (Phila). 2013;8: 332–6.