Search

Introduction: Apela has a wide range of biological effects on the cardiovascular system, but the changes and significance of endogenous Apela in patients with chronic heart failure (CHF) and acute deterioration of cardiac and renal function are unclear. Methods: A total of 69 patients with stable CHF combined with well-preserved renal function were enrolled and followed for 12 months. The effects of Apela on human renal glomerular endothelial cells (hRGEC), human glomerular mesangial cells (hMC), and human renal tubular epithelial cells (HK-2) were observed. Results: Serum Apela concentration was positively correlated with NYHA class (r = 0.711) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration (r = 0.303) but negatively correlated with left ventricular ejection fraction (LVEF) (r = −0.374) and 6-min walk distance (r = −0.860) in patients with stable CHF. Twenty-one patients experiencing deterioration of renal and cardiac function were diagnosed with cardiorenal syndrome (CRS) during the follow-up period. In addition, the serum Apela, as well as the difference in Apela between stable and worsening phases (ΔApela), was correlated with the estimated glomerular filtration rate (eGFR) and ΔeGFR in patients with CRS. Apela significantly inhibited the upregulated expression of MCP-1 and TNF-α induced by angiotensin II (AngII) in hRGEC, hMC, and HK-2 cells. Apela inhibited the adhesion of THP-1 cells to hRGEC and promoted the tubular formation of hRGEC. Moreover, Apela enhanced the expression of MMP-9 in hMC but inhibited the upregulated expression of α-SMA and vimentin in HK-2 cells by AngII. Conclusion: This study suggests that the level of Apela can be used to diagnose heart failure and assess the severity of cardiac dysfunction in patients with stable CHF, and its dynamic changes can be used to evaluate the damage to renal function in patients with CRS. Apela plays multiple protective effects on renal cells, highlighting its clinical application prospect in the prevention and treatment of CRS. [ABSTRACT FROM AUTHOR]

Aim: In this subgroup analysis of STRONG‐HF, we explored the association between changes in renal function and efficacy of rapid up‐titration of guideline‐directed medical therapy (GDMT) according to a high‐intensity care (HIC) strategy. Methods and results: In patients randomized to the HIC arm (n = 542), renal function was assessed at baseline and during follow‐up visits. We studied the association with clinical characteristics and outcomes of a decrease in estimated glomerular filtration rate (eGFR) at week 1, defined as ≥15% decrease from baseline. Patients in the usual care group (n = 536) were seen at day 90. The treatment effect of HIC versus usual care was independent of baseline eGFR (p‐interaction = 0.4809). A decrease in eGFR within 1 week occurred in 77 (15.5%) patients and was associated with more rales on examination (p = 0.004), and a higher New York Heart Association class at the corresponding visit. Following the decrease in eGFR at 1 week, lower average optimal doses of GDMT were prescribed during follow‐up (p = 0.0210) and smaller reductions in N‐terminal pro‐B‐type natriuretic peptide occurred (geometrical mean 0.81 in no eGFR decrease vs 1.12 in GFR decrease, p = 0.0003). The rate of heart failure (HF) readmission or death at 180 days was 12.3% in no eGFR decrease versus 18.5% in eGFR decrease (p = 0.2274) and HF readmissions were 7.8% versus 16.6% (p = 0.0496). Conclusions: In the STRONG‐HF study, HIC reduced 180‐day HF readmission or death regardless of baseline eGFR. An early decrease in eGFR during rapid up‐titration of GDMT was associated with more evidence of congestion, yet lower doses of GDMT during follow‐up. [ABSTRACT FROM AUTHOR]

Introduction: The risk of unfavourable outcomes after an acute heart failure (AHF) episode remains high. Effective decongestion, reflected by haemoconcentration (HC), may guide therapy. Optimal timing of HC remains unspecified. Methods: We analysed the AHF registry to evaluate the prognostic differences of various timing of HC. Subjects were divided into 3 groups by time of reaching HC. Results: The groups differed in terms of 1-year occurrence of a composite of the mortality and AHF hospitalization (26% vs. 46% vs. 40%, early vs. late vs. no HC, p = 0.016). Conclusions: Patients reaching HC earlier seem to present the best prognosis regarding the analysed composite endpoint. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is the common final pathway of several conditions and is characterized by hyperactivation of numerous neurohumoral pathways. Cardiorenal interaction plays an essential role in the progression of the disease, and the use of diuretics is a cornerstone in the treatment of hypervolemic patients, especially in acute decompensated HF (ADHF). The management of congestion is complex and, to avoid misinterpretations and errors, one must understand the interface between the heart and the kidneys in ADHF. Congestion itself may impair renal function and must be treated aggressively. Transitory elevations in serum creatinine during decongestion is not associated with worse outcomes and diuretics should be maintained in patients with clear hypervolemia. Monitoring urinary sodium after diuretic administration seems to improve the response to diuretics as it allows for adjustments in doses and a personalized approach. Adequate assessment of volemia and the introduction and titration of guideline-directed medical therapy are mandatory before discharge. An early visit after discharge is highly recommended, to assess for residual congestion and thus avoid readmissions. [ABSTRACT FROM AUTHOR]

Cardiovascular mortality is a leading cause of death in chronic kidney disease (CKD), as is IgA nephropathy (IgAN). The purpose of this study is to find different biomarkers to estimate the outcome of the disease, which is significantly influenced by the changes in vessels (characterized by arterial stiffness) and the heart. In our cross-sectional study, 90 patients with IgAN were examined. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was measured as a heart failure biomarker by an automated immonoassay method, while the carboxy-terminal telopeptide of collagen type I (CITP) as a fibrosis marker was determined using ELISA kits. Arterial stiffness was determined by measuring carotid–femoral pulse wave velocity (cfPWV). Renal function and routine echocardiography examinations were performed as well. Based on eGFR, patients were separated into two categories, CKD 1-2 and CKD 3-5. There were significantly higher NT-proBNP (p = 0.035), cfPWV (p = 0.004), and central aortic systolic pressure (p = 0.037), but not CITP, in the CKD 3-5 group. Both biomarker positivities were significantly higher in the CKD 3-5 group (p = 0.035) compared to the CKD 1-2 group. The central aortic systolic pressure was significantly higher in the diastolic dysfunction group (p = 0.034), while the systolic blood pressure was not. eGFR and hemoglobin levels showed a strong negative correlation, while left ventricular mass index (LVMI), aortic pulse pressure, central aortic systolic pressure, and cfPWV showed a positive correlation with NT-proBNP. cfPWV, aortic pulse pressure, and LVMI showed a strong positive correlation with CITP. Only eGFR was an independent predictor of NT-proBNP by linear regression analysis. NT-proBNP and CITP biomarkers may help to identify IgAN patients at high risk for subclinical heart failure and further atherosclerotic disease. [ABSTRACT FROM AUTHOR]

The role of risk scores in heart failure (HF) management has been highlighted by international guidelines. In contrast with HF, which is intrinsically a dynamic and unstable syndrome, all its prognostic studies have been based on a single evaluation. We investigated whether time-related changes of a well-recognized risk score, the MECKI score, added prognostic value. MECKI score is based on peak VO 2 , VE/VCO 2 slope, Na+, LVEF, MDRD and Hb. A multi-centre retrospective study was conducted involving 660 patients who performed MECKI re-evaluation at least 6 months apart. Based on the difference between II and I evaluation of MECKI values (MECKI II – MECKI I = ∆ MECKI) the study population was divided in 2 groups: those presenting a score reduction (∆ MECKI <0, i.e. clinical improvement), vs. patients presenting an increase (∆ MECKI >0, clinical deterioration). The prognostic value of MECKI score is confirmed also when re-assessed during follow-up. The group with improved MECKI (366 patients) showed a better prognosis compared to patients with worsened MECKI (294 patients) (p < 0.0001). At 1st evaluation, the two groups differentiated by LVEF, V E /VCO 2 slope and blood Na+ concentration, while at 2nd evaluation they differentiated in all 6 parameters considered in the score. The patients who improved MECKI score, improved in all components of the score but hemoglobin, while patients who worsened the score, worsened all parameters. This study shows that re-assessment of MECKI score identifies HF subjects at higher risk and that score improvement or deterioration regards several MECKI score generating parameters confirming the holistic background of HF. • International guidelines have highlighted the role of risk scores in heart failure (HF). • MECKI score is one of the prognostic models recommended by the European HF guidelines. • Although HF is a dynamic syndrome, prognostic studies have been based on a single evaluation. • The prognostic power of MECKI score is confirmed at a II evaluation during follow up. • Re -evaluation of MECKI score during follow up identifies HF subjects at higher risk. [ABSTRACT FROM AUTHOR]

Background: Impaired renal function is 1 of the poor prognostic factors in dogs with myxomatous mitral valve disease (MMVD). However, the value of cystatin C (Cys‐C), a marker of renal function, as a prognostic marker for MMVD in dogs has not yet been explored. Objective: This study aims to investigate the prognostic value of Cys‐C in dogs with MMVD. Animals: Fifty client‐owned small‐breed dogs with MMVD were included in this study. Methods: This is a retrospective, cross‐sectional study. The prognostic value of serum Cys‐C concentration was assessed using univariable and multivariable Cox hazard regression analyses. Kaplan‐Meier survival curves for MMVD‐specific survival in dogs stratified into high and low Cys‐C groups were generated and analyzed using the log‐rank test. Results: Serum Cys‐C concentrations were significantly associated with MMVD‐related death (P <.01) in both univariable (hazard ratio [HR], 5.086; 95% confidence interval [CI], 1.950‐13.270) and multivariable Cox hazard regression analysis (HR, 4.657; 95% CI, 1.767‐12.270). The high Cys‐C group (n = 14) had a significantly shorter MMVD‐specific survival time than the low Cys‐C group (n = 36; P <.01). In dogs with normal blood creatinine concentrations, the high Cys‐C group (n = 10) had a significantly shorter MMVD‐specific survival time than the low Cys‐C group (n = 36; P <.01). Conclusions and Clinical Importance: High serum Cys‐C concentrations were associated with a worse prognosis of MMVD. Furthermore, serum Cys‐C could be a predictor of MMVD prognosis even in dogs with normal blood creatinine concentration. [ABSTRACT FROM AUTHOR]

The cardio-renal syndrome (CRS) type 2 is defined as a progressive loss of renal function following a primary insult to the myocardium that may be either acute or chronic but is accompanied by a decline in myocardial pump performance. The treatment of patients with CRS is difficult, and the disease often progresses to end-stage renal disease that is refractory to conventional therapy. While a good deal of information is known concerning renal injury in the CRS, less is understood about how reflex control of renal sympathetic nerve activity affects this syndrome. In this review, we provide insight into the role of the renal nerves, both from the afferent or sensory side and from the efferent side, in mediating renal dysfunction in CRS. We discuss how interventions such as renal denervation and abrogation of systemic reflexes may be used to alleviate renal dysfunction in the setting of chronic heart failure. We specifically focus on a novel cardiac sensory reflex that is sensitized in heart failure and activates the sympathetic nervous system, especially outflow to the kidney. This so-called Cardiac Sympathetic Afferent Reflex (CSAR) can be ablated using the potent neurotoxin resinferitoxin due to the high expression of Transient Receptor Potential Vanilloid 1 (TRPV1) receptors. Following ablation of the CSAR, several markers of renal dysfunction are reversed in the post-myocardial infarction heart failure state. This review puts forth the novel idea of neuromodulation at the cardiac level in the treatment of CRS Type 2. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome (CRS) is a complex, heterogeneous spectrum of symptoms that has kept cardiologists awake for decades. The heart failure (HF) population being burdened with multimorbidity poses diagnostic and therapeutic challenges even for experienced clinicians. Adding deteriorated renal function to the equation, which is one of the strongest predictors of adverse outcome, we measure ourselves against possibly the biggest problem in modern cardiology. With the rapid development of new renal assessment methods, we can treat CRS more effectively than ever. The presented review focuses on explaining the pathophysiology, recent advances and current practices of monitoring renal function in patients with acute CRS. Understanding the dynamic interaction between the heart and the kidney may improve patient care and support the selection of an effective and nephroprotective treatment strategy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To dynamically analyze the effects of leosimendan combined with dopamine on renal function in patients with acute heart failure based on DID model. METHODS: A total of 225 patients with acute heart failure admitted to this hospital from Jan. 2019 to Jan. 2021 were divided into research group (112 cases) and control group (113 cases) via the random number table. The control group was given conventional therapy for cardiac failure combined with dopamine for intravenous pump [ from 1 to 5 μg / ( kg·min)]; while the research group was given leosimendan based on the control group, with the initial loading dosage (12 μg / kg) administrated intravenously for 10 min, followed by intravenous drip at the velocity of 0. 1 μg / ( kg·min) for cardiac tonic treatment. Indicators of renal function and cardiac function were compared between two groups before and after treatment, the clinical efficacy of levosimendan was evaluated by using the DID method, and the parallel trend test graphs were plotted by using the Coefplot package in Stata software. RESULTS: After 1, 2, 3 and 4 weeks of treatment, the left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac index (CI) and glomerular filtration rate (GFR) of both groups were significantly higher than those before treatment, the blood urea nitrogen (BUN), serum creatinine ( SCr) and Nterminal B-type natriuretic peptidogen (NT-proBNP) levels of both groups were significantly lower than those before treatment; after 1, 2 and 3 weeks of treatment, the LVEF, SV, CI and GFR levels of the research group were significantly higher than those of the control group, the BUN, SCr and NT-proBNP levels of research group were significantly lower than those of the control group, with statistically significant differences (P<0. 05); after 4 weeks of treatment, there were no significant difference in the above indexes between the two groups (P>0. 05). The results of DID effect analysis showed that there was a statistically significant improvement in cardiac and renal function between the treatment regimen and the AHF patients (P<0. 05). CONCLUSIONS: Levosimendan combined with dobutamine can improve early renal function, increase cardiac function and left ventricular activity in patients with acute heart failure. [ABSTRACT FROM AUTHOR]

Background: Kidney injury (KI) has been documented in dogs treated with furosemide for left‐sided congestive heart failure (CHF). Hypothesis/Objectives: Determine risk factors for development of KI in furosemide‐treated dogs and determine the effect of KI on survival. Animals: Seventy‐nine client‐owned dogs receiving parenteral furosemide for CHF. Methods: Serum creatinine (sCr) and electrolyte concentrations were determined during hospitalization and at first outpatient reevaluation to detect and stage KI (increase in sCr ≥0.3 mg/dL). Furosemide dosage administered between timepoints was calculated. Multivariable modeling was performed to identify predictors of KI and percent change in serum biochemistry results over time. Results: Kidney injury was identified in 38/79 (48%) dogs and mostly occurred during hospitalization. Kidney injury was Grade I in 25 dogs, Grade II in 9 dogs, and Grade III in 4 dogs. Higher blood pressure was associated with acute KI during hospitalization (odds ratio, 1.03; 95% confidence interval [95% CI] 1.01‐1.07; P =.03) whereas PO furosemide dosage was associated with KI after hospital discharge (odds ratio, 7.77; 95% CI, 2.05‐68.6; P =.02). Baseline sCr and use of a furosemide continuous rate infusion were not associated with increased risk of KI. Kidney injury was not associated with long‐term outcome. Of 13 dogs with Grade II‐III KI, azotemia was reversible in 9 dogs, and 6 dogs survived >1 year after KI. Conclusions and Clinical Importance: In this cohort of dogs receiving parenteral furosemide for CHF, KI was common, mostly nonazotemic (Grade I), and did not impact survival. [ABSTRACT FROM AUTHOR]

The impact of increasing temperatures on renal function in heart failure (HF) outpatients has never been specifically analyzed. We retrieved creatinine and estimated glomerular filtration rate (eGFR) values of all HF outpatients followed at a HF clinic and temperature data from 2002 to 2021. For each patient and each year we averaged values of creatinine, eGFR and monthly temperatures during summer and the rest of the year. The study cohort included 2167 HF patients undergoing 25,865 elective visits, with a median of 14 visits for each patient (interquartile range 7–23). At the first visit, patients (70% men) had an age of 67 ± 13 years, and a left ventricular ejection fraction of 35 ± 14%. Creatinine was 1.25 ± 0.51 mg/dL, and eGFR was 65 ± 25 mL/min/1.73 m2. When pooling together all average values of creatinine and eGFR measured during summer or in the rest of the year, creatinine was significantly higher in summer (difference 0.04, 95% confidence interval [CI] 0.04 to 0.05, p < 0.001), and eGFR was slightly lower (difference − 2.0, 95% CI -2.3 to −1.8, p < 0.001). Temperature rise during summer increased from 2002 to 2021. The absolute (Δ) and percent (Δ%) elevation in temperature during summer displayed independent associations with Δ and Δ% creatinine and eGFR after adjusting for age, sex, plasma creatinine, and HF therapies. The magnitude of temperature elevation during summer has increased over 20 years. This elevation correlates with the decline in renal function during summer. This might be an example of how global warming is affecting human health. Temperature elevation during summer and worsening renal function over a 20-year timespan The graph is a schematic representation of the changes in temperatures and renal function over time and not an accurate representation. eGFR, estimated glomerular filtration rate; HF, heart failure. [Display omitted] • This study cohort included 2167 HF patients undergoing 25,865 elective visits. • The magnitude of temperature elevation during summer has increased over 20 years. • This elevation correlates with the decline in renal function during summer. [ABSTRACT FROM AUTHOR]

Background: Chronic heart failure (HF) is known to increase the risk of developing Alzheimer's dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood. Methods: Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI). Results: Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = − 0.21; p = 0.013) and pTau (ρ = − 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = − 2.4 for pTau; T = − 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = − 3.1). Conclusions: pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers. [ABSTRACT FROM AUTHOR]

There are limited data about postoperative changes in hepatic and renal function in adults with congenital heart disease (CHD) undergoing isolated heart transplant. The purpose of this study was to assess postoperative changes in hepatic and renal function in this population. Retrospective cohort study of adults with CHD undergoing isolated heart transplant at Mayo Clinic (2003–2019). Global hepatic function was assessed using the model for end-stage liver disease excluding international normalized ratio [MELD-XI]) score; hepatic fibrosis was assessed using the fibrosis-4 (FIB-4) score and aspartate/platelet ratio index (APRI); and renal function was assessed using estimated glomerular filtration rate (GFR). All indices were measured preoperatively and postoperatively (at 6 months, 1 year, 2 years). Of 40 patients (age 41 ± 8 years) in the study, 35 had complete preoperative and postoperative data. There was a temporal improvement in hepatic and renal indices from preop (MELD-XI 14 ± 5, APRI 0.60 ± 0.23, FIB-4 1.44 ± 0.38, GFR 59 [44–83]) to 6 months postop (MELD-XI 12 ± 6, APRI 0.49 ± 0.17, FIB-4 1.29 ± 0.33, GFR 68 [54–96]) and 1-year postop (MELD-XI 9 ± 3, APRI 0.41 ± 0.16, FIB-4 1.12 ± 0.29, GFR 82 [69–108]), p < 0.05 for all comparisons. CHD patients undergoing isolated heart transplant had significant improvement in hepatic and renal function. These data suggests that selected CHD patients may do well with isolated heart transplant despite reduced hepatic and renal function, and hepatic fibrosis preoperatively. More rigorous prospective studies are required to determine the relative outcomes of isolated versus combined heart-liver transplant in this population. • Adults with CHD undergoing isolated heart transplant had significant improvement in hepatic and renal function. • There was a continuous improvement in hepatic and renal function for several months after normalization of cardiac hemodynamics. • Selected CHD patients with hepatic and renal dysfunction may do well with isolated heart transplant alone. [ABSTRACT FROM AUTHOR]

Blood urea nitrogen (BUN) reflects decreased glomerular filtration rate (GFR). The effect of BUN on clinical outcomes, excluding the impact of GFR, in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. We enrolled HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure (HF) from PURSUIT-HFpEF registry which was prospective, multicenter and observational study. For excluding the effect of renal function on BUN value, propensity score-matching was performed using the variables which were associated with GFR. The incidence of composite of all-cause death and HF readmission among the patients stratified by BUN and the association between BUN and echocardiographic parameters in HFpEF patients were evaluated. We finally analyzed 1029 patients. In the present study, BUN cut-off value was defined as 24.4 mg/dL, which was the median value in overall population. The high and low BUN groups consisted of 193 patients after 1:1 propensity score-matching, respectively. The median follow-up duration was 401 days and the composite endpoint occurred in 129 patients (33.4%). Kaplan-Meier analysis showed the high BUN group had a significantly greater risk of the composite endpoint than the low group in the propensity score-matched pairs (p = 0.032). BUN value significantly correlated with left atrial volume index by multiple regression analysis using echocardiographic parameters (standardized beta-coefficient = 0.139, p = 0.043). BUN was a useful marker for the composite of all-cause death and HF readmission, regardless of the baseline renal function and correlated with left atrial function in HFpEF patients. UMIN000021831 < https://uplaod.umin.ac.jp/cgi-open-bin/ctr%5fe/ctr%5fview.cgi?recptno=R00002441 4>; PURSUIT-HFpEF. • High BUN was associated with the composite of all-cause death and HF readmission in HFpEF. • BUN affects clinical outcomes, regardless of renal function. • BUN correlated with left atrial dysfunction in HFpEF. [ABSTRACT FROM AUTHOR]

Aims: Physicians are sometimes reluctant to initiate guideline-directed therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to concerns of adverse events. We explored the risk of hypotension, volume depletion, and acute kidney injury (AKI) on sodium-glucose cotransporter 2 (SGLT2) inhibitors in HFrEF populations.Methods and Results: We determined summary risk ratios (RRs) by conducting a meta-analysis on reported aforementioned adverse events on SGLT2 inhibitors from randomized controlled trials. We explored robustness of meta-analyses by computing fragility and/or reverse fragility index (FI or RFI) and its corresponding fragility quotient (FQ or RFQ) for each outcome. A total of 10 050 patients with HFrEF entered the final meta-analysis. Hypotension was reported in 4.5% (219/4836) on SGLT2 inhibitors and in 4.1% (202/4846) on placebo (RR 1.09, 95% confidence interval [CI] 0.91-1.31, p = 0.36). An RFI of 21 and RFQ of 0.002 suggest robust findings for hypotension. Volume depletion occurred in 9.4% (473/5019) on SGLT2 inhibitors and in 8.7% (438/5031) on placebo (RR 1.07, 95% CI 0.95-1.21, p = 0.25), respectively. RFI of 19 and RFQ of 0.001 suggest moderately robust findings for volume depletion. AKI was reported in fewer patients (1.9% [95/4888]) on SGLT2 inhibitors than on placebo (2.8% [140/4899]) providing lower incidence of AKI (RR 0.69, 95% CI 0.51-0.93, p = 0.02). FI of 14 and RFQ of 0.001 suggest moderately robust findings for AKI.Conclusion: Sodium-glucose cotransporter 2 inhibitor therapy is not associated with a clinically relevant risk of hypotension and volume depletion. Its use reduces the risk of AKI. This analysis supports current guideline recommendations on early use of SGLT2 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of hospitalization for heart failure (HF) or death from cardiovascular causes among patients with chronic HF. However, little is known about the specific factors associated with clinical events during SGLT2i therapy in patients hospitalized for acute decompensated heart failure (ADHF). Methods: Consecutive patients who were hospitalized for ADHF and received SGLT2i during the index hospitalization between February 2016 and April 2021 were retrospectively evaluated. We investigated the factors associated with recurrent hospitalization for HF during the SGLT2i therapy. Results: A total of 143 patients (median age 73 years, 92 men) were included. Estimated glomerular filtration rate (eGFR) was negatively associated with a primary endpoint with a hazard ratio of 0.94 (95% confidence interval 0.90–0.98, p = 0.007). Those with lower eGFR < 40.9 mL/min/1.73 m2 (n = 47) had significantly lower freedom from HF hospitalization during 1-year therapeutic period (73% versus 94%, p = 0.005). Conclusions: Among patients who initiated medical therapy incorporating SGLT2i during the hospitalization for ADHF, a lower eGFR at baseline was associated with a recurrent hospitalization for HF. Early administration of SGLT2i prior to deterioration of renal function would be highly recommended to enjoy greater benefit from SGLT2i. [ABSTRACT FROM AUTHOR]

Novel pharmacologic treatment options reduce mortality and morbidity in a cost‐effective manner in patients with heart failure (HF). Undisputedly, the effective implementation of these agents is an essential element of good clinical practice, which is endorsed by the European Society of Cardiology (ESC) guidelines on acute and chronic HF. Yet, physicians struggle to implement these therapies as they have to balance the true and/or perceived risks versus their substantial benefits in clinical practice. Any worsening of biomarkers of renal function is often perceived as being disadvantageous and is in clinical practice one of the most common reasons for ineffective drug implementation. However, even in this context, they clearly reduce mortality and morbidity in HF with reduced ejection fraction (HFrEF) patients, even in patients with poor renal function. Furthermore these agents are also beneficial in HF with mildly reduced ejection fraction (HFmrEF) and sodium–glucose cotransporter 2 (SGLT2) inhibitors more recently demonstrated a beneficial effect in HF with preserved ejection fraction (HFpEF). The emerge of several new classes (angiotensin receptor–neprilysin inhibitor [ARNI], SGLT2 inhibitors, vericiguat, omecamtiv mecarbil) and the recommendation by the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic HF of early initiation and titration of quadruple disease‐modifying therapies (ARNI/angiotensin‐converting enzyme inhibitor + beta‐blocker + mineralocorticoid receptor antagonist and SGLT2 inhibitor) in HFrEF increases the likelihood of treatment‐induced changes in renal function. This may be (incorrectly) perceived as deleterious, resulting in inertia of starting and uptitrating these lifesaving therapies. Therefore, the objective of this consensus document is to provide advice of the effect HF drugs on renal function. [ABSTRACT FROM AUTHOR]

Aims: Vericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m2. We evaluated the relationship between the efficacy of vericiguat and baseline and subsequent changes in renal function. Methods and results: In VICTORIA, core laboratory serum creatinine was measured at baseline (n = 4956) and weeks 16, 32, and 48. Worsening renal function (WRF), defined as an increase ≥0.3 mg/dL in creatinine from baseline to week 16, was assessed via a Cox model with respect to subsequent primary events. Mean age was 69 years, 24% were female, and mean baseline eGFR was 61 mL/min/1.73 m2. During 48 weeks of treatment, the trajectories in eGFR and creatinine with vericiguat were similar to placebo (P = 0.50 and 0.18). The beneficial effects of vericiguat on the primary outcome were not influenced by baseline eGFR (interaction P = 0.48). WRF occurred in 15% of patients and was associated with worse outcomes (adjusted hazard ratio 1.28, 95% confidence interval 1.11–1.47; P < 0.001), but the beneficial effects of vericiguat on the primary outcome were similar in patients with or without WRF (interaction P = 0.76). Conclusion: Renal function trajectories were similar between vericiguat‐ and placebo‐treated patients and the beneficial effects of vericiguat on the primary outcome were consistent across the full range of eGFR and irrespective of WRF. [ABSTRACT FROM AUTHOR]

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of tolvaptan (average dose, 7.8 mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784 days (3.3 and 2.1 years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, − 8.02 ± 9.35 to − 1.62 ± 5.09 mL/min/1.73m2 /year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients. [ABSTRACT FROM AUTHOR]

Aims: In acute heart failure (AHF), assessment of renal function comprises estimation of glomerular filtration rate (eGFR), which does not provide any information about renal sodium/water handling. We describe the interactions between urinary sodium concentration and eGFR to better characterize AHF patients. Methods and results: In 219 patients with AHF, spot urine sodium (UNa+) and eGFR were assessed on admission, day 1 and day 2 of hospitalization. We found no correlation between UNa+ and eGFR (calculated on each consecutive day, as an average of all three values, and as changes from baseline; all P > 0.05). The population was subsequently divided into four profiles based on eGFR (preserved vs. impaired; cutoff of 60 mL/min/1.73 m2) and UNa+ (sodium excreter vs. non‐excreter; cutoff of 60 mmol/L). At day 1, there were 70 (31.9%) patients classified as preserved eGFR/sodium excreter, 37 (16.8%) as impaired eGFR/sodium non‐excreter, 72 (32.9%) as impaired eGFR/sodium excreter, and 40 (18%) as preserved eGFR/sodium non‐excreter. Both sodium non‐excreter profiles were associated with an increased risk of in‐hospital heart failure worsening [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.3–6.4], inotrope use (OR 2.6, 95% CI 1.1–6.7) and rehospitalization due to AHF (OR 3.2, 95% CI 1.6–6.2; all P < 0.05). The preserved eGFR/sodium non‐excreter profile was associated with highest 1‐year mortality (52.5%) and remained an independent prognosticator after adjustment for other prognosticators (hazard ratio 2.9, 95% CI 1.7–5.2; P < 0.0005). Conclusions: In AHF, values of spot UNa+ and eGFR are not interrelated. Concomitant assessment of eGFR and spot UNa+ may be useful for better clinical and therapeutic profiling of patients. [ABSTRACT FROM AUTHOR]

Aims: To characterize the prevalence and clinical relevance of malnutrition in patients undergoing transcatheter tricuspid valve edge-to-edge repair (TTVR).Methods and Results: Overall, 86 consecutive patients (mean age 78 ± 7 years) with moderate-to-severe tricuspid regurgitation (TR) at prohibitive surgical risk were analysed. Mini Nutritional Assessment (MNA), quality of life assessment, 6-min walk test distance and laboratory analyses were performed before and 1 month after TTVR. A total of 43 patients (50%) underwent concomitant transcatheter mitral valve repair. According to MNA, 81 patients (94%) were malnourished or at risk of malnutrition before TTVR. Following TTVR, MNA improved in 64 patients (74%). As compared to patients without MNA improvement, patients with increased MNA score had greater reductions in TR [regurgitation volume -17.0 (interquartile range, IQR -25.0; -7.0) mL vs. -26.4 (IQR -40.3; -14.5) mL, P < 0.001] and inferior vena cava diameter. Only patients with increased MNA score displayed a decrease in N-terminal pro-brain natriuretic peptide levels [-320 (IQR -1294; 105) pg/mL vs. +708 (IQR -342; 2708) pg/mL, P = 0.009], improvements in cholinesterase levels (0.0 ± 11.9 μmoL/L vs. +10.9 ± 16.7 μmoL/L, P < 0.001) and renal function during follow-up. Beneficial effects on quality of life scores and 6-min walk test distance following TTVR were observed exclusively in patients with improvement in MNA. During a median follow-up of 6 months, patients with worsened MNA had an increased risk of death and rehospitalization for heart failure.Conclusion: Nutritional impairment is common and of prognostic importance in patients undergoing TTVR. Hepatorenal function modestly improves after successful TTVR. Further study of extracardiac implications of TR-associated right heart failure is warranted to improve care in this vulnerable patient population. [ABSTRACT FROM AUTHOR]

Background: Hyponatraemia predicts type 1 cardiorenal syndrome in acute decompensated heart failure patients, which associates with poor outcome. Recovery from hyponatraemia has been found to associate with better outcome in acute decompensated heart failure patients, but its prognostic value regarding renal function remains unknown. Methods: We performed a secondary analysis of CARRESS‐HF trial, and all patients included had worsening renal function (≥0.3 mg/dL increase in serum creatinine than the nadir). The serum sodium levels of patients were evaluated at baseline and day 4 and day 7 after randomization. Patients were grouped according to the status of hyponatraemia: recovery from hyponatraemia; no hyponatraemia; persistent hyponatraemia; and new‐onset hyponatraemia. Their associations with persistent worsening renal function (serum creatinine ≥ 0.3 mg/dL higher than the nadir at discharge) were explored. Results: A total of 118 patients suffered from persistent worsening renal function. Baseline hyponatraemia was not associated with persistent worsening renal function (odds ratio = 0.495, P =.086). Patients in the recovery from hyponatraemia group had a lowest risk of persistent worsening renal function among the study population. Further, baseline serum sodium level was not associated with the risk of persistent worsening renal function (odds ratio = 1.055, P =.233), while the increases in serum sodium level at day 4 (odds ratio = 0.858, P =.003) and at day 7 (odds ratio = 0.821, P <.001) significantly predicted a lower risk of persistent worsening renal function. Conclusions: Recovery from hyponatraemia associates with a lower risk of persistent worsening renal function, suggesting that hyponatraemia correction may improve renal outcomes in acute decompensated heart failure patients with type 1 cardiorenal syndrome. [ABSTRACT FROM AUTHOR]

• Pre-hospital renal function levels improve acute kidney injury identification. • Acute kidney injury is already present at admission in a large number of patients. • Worse clinical outcomes are associated with pre-hospital renal function. • Acute kidney injury at admission identifies patients with worse prognosis. Acute kidney injury (AKI) is a serious complication in patients hospitalized for decompensated heart failure (HF). Currently, AKI definitions consider creatinine levels at admission as reference of baseline renal function (RF). However, renal impairment may already be present at admission. We aimed to study the impact on AKI detection of considering outpatient RF as reference. In a cohort of 458 patients hospitalized for decompensated HF, we studied the occurrence of AKI using the standardized KDIGO criteria and grading (stages: 1, 2, 3), and considering two different definitions according to the RF used as reference or baseline: the latest outpatient measurement prior to admission vs. the first measurement at admission. We compared the prevalence, timing and prognostic value for both AKI definitions. The definition based on outpatient RF was associated with an increase in overall AKI detection from 20.1% to 33.8% (p < 0.001), and from 3.1% to 5.0% for advanced stages (2–3) (p < 0.001); additionally, 12.5% of patients already had criteria of AKI at admission (36.8% of AKI cases). Both definitions were associated with longer hospital stay. However, only AKI already present at admission, as based on pre-hospital creatinine, was independently associated with all-cause death, in-hospital and after discharge, and death or HF readmission in the follow-up: 1 stage (HR 2.72, 95%CI 1.83–4.06, p < 0.001) and 2–3 stage (HR 7.29, 95%CI, 3.02–17.64, p < 0.001). Evaluation of AKI in patients admitted with HF should consider pre-hospital RF, since it improves early identification of AKI and has implications for risk assessment. [ABSTRACT FROM AUTHOR]

Aims: Inhibition of sodium-glucose co-transporter 2 (SGLT2) reduces the risk of death and heart failure (HF) admissions in patients with chronic HF. However, safety and clinical efficacy of SGLT2 inhibitors in patients with acute decompensated HF are unknown.Methods and Results: In this randomized, placebo-controlled, double-blind, parallel group, multicentre pilot study, we randomized 80 acute HF patients with and without diabetes to either empagliflozin 10 mg/day or placebo for 30 days. The primary outcomes were change in visual analogue scale (VAS) dyspnoea score, diuretic response (weight change per 40 mg furosemide), change in N-terminal pro brain natriuretic peptide (NT-proBNP), and length of stay. Secondary outcomes included safety and clinical endpoints. Mean age was 76 years, 33% were female, 47% had de novo HF and median NT-proBNP was 5236 pg/mL. No difference was observed in VAS dyspnoea score, diuretic response, length of stay, or change in NT-proBNP between empagliflozin and placebo. Empagliflozin reduced a combined endpoint of in-hospital worsening HF, rehospitalization for HF or death at 60 days compared with placebo [4 (10%) vs. 13 (33%); P = 0.014]. Urinary output up until day 4 was significantly greater with empagliflozin vs. placebo [difference 3449 (95% confidence interval 578-6321) mL; P < 0.01]. Empagliflozin was safe, well tolerated, and had no adverse effects on blood pressure or renal function.Conclusions: In patients with acute HF, treatment with empagliflozin had no effect on change in VAS dyspnoea, diuretic response, NT-proBNP, and length of hospital stay, but was safe, increased urinary output and reduced a combined endpoint of worsening HF, rehospitalization for HF or death at 60 days. [ABSTRACT FROM AUTHOR]

Changes in the regulatory guidelines by the U.S. Food and Drug Administration and the European Medical Agency requiring large-scale trials that study the cardiovascular safety of new glucose-lowering drugs have improved our understanding of type 2 diabetes mellitus. Unexpectedly, these trials demonstrated that sodium-glucose cotransporter 2 inhibitors reduce adverse cardiovascular outcomes. This second part of this 2-part review summarizes the findings of recent clinical trials and their clinical implications and describes ongoing trials and future areas of research. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class approved for treatment of diabetes, have been shown to possess a favorable metabolic profile and to significantly reduce atherosclerotic events, hospitalization for heart failure, cardiovascular and total mortality, and progression of chronic kidney disease. Although initially considered to be only glucose-lowering agents, the effects of SGLT2i have expanded far beyond that, and their use is now being studied in the treatment of heart failure and chronic kidney disease, even in patients without diabetes. It is therefore critical for cardiologists, diabetologists, nephrologists, and primary care physicians to be familiar with this drug class. This first part of this 2-part review provides an overview of the current understanding of the mechanisms of the cardio-metabolic-renal benefits of SGLT2i. The second part summarizes the recent clinical trials of SGLT2i. [ABSTRACT FROM AUTHOR]

Background: In heart failure (HF) patients with renal insufficiency (RI), we hypothesize that mechanical circulatory support (MCS) with the left ventricular assist device (LVAD) will promote renal function recovery (RR). We sought to quantify RR with LVAD support over 6 months of follow-up.Methods: RR data at 30, 90, and 180 days were analyzed for all LVAD patients with RI at the time of surgery. RI was defined as either the use of hemodialysis (HD) or a glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 .Results: Between January 2008 and December 2013, 47 of 127 (37%) LVAD recipients had RI at the time of surgery. The mean preoperative GFR was 48 ± 7. We observed RR at each follow-up, with 30-, 90-, and 180-day mean GFRs of 79 ± 33, 71 ± 31, and 63 ± 21, respectively. The absolute increase in GFR at 30, 90, and 180 days was 34 ± 31, 26 ± 29, and 19 ± 20, respectively (All with P < .001). Four patients (8.5%) with RI required HD preoperatively. Of these, three recovered renal function, the fourth patient died. An additional 13 patients (30.2%) that were previously non-HD-dependent required HD postoperatively. Six of these 13 (46%) recovered renal function during the study period, four (30.7%) remain on HD and three (23%) died.Conclusions: RI improves significantly with LVAD support. Improvements in GFR are marked in the first 30 days. Among those patients requiring either pre- or post-operative HD, a majority recovered renal function. [ABSTRACT FROM AUTHOR]

Background: Self-care is assumed to benefit physiological function associated with prognosis in patients with chronic HF, but studies examining these relations are lacking. This study aims to prospectively examine the association of self-reported HF self-care with HF-associated pathophysiological markers, including renal, hematological, and immune function. Method: Patients with chronic HF (n = 460, 66.2 ± 9.6 years, 75% men) completed questionnaires and provided blood samples at baseline and 12-month follow-up. Linear mixed models examined random intercept and fixed between- and within-subjects effects of global self-care and the individual self-care behaviors on log-transformed TNF-α, IL-6, and IL-10, the glomerular filtration rate of creatinine (GFRcreat), and hemoglobin (Hb), controlling for sociodemographic and clinical covariates. Results: Self-care was independently associated with lower GFRcreat levels (β = −.14, P =.023) and improvement in self-care with a reduction in GFRcreat (β = −.03, P =.042). Individual self-care behaviors were differentially associated with renal, inflammatory, and hematological markers. Regular exercise was associated with level differences in IL-6 (P <.001), and improvement in exercise was associated with increasing GFRcreat (P =.002) and increasing Hb (P =.010). Fluid restriction was associated with lower overall GFRcreat (P =.006), and improvement in fluid restriction was associated with decreasing GFRcreat (P =.014). Low-sodium intake was associated with lower levels of Hb (P =.027), lower TNF-alpha (P =.011), and lower IL-10 (P =.029). Higher levels of medication adherence were associated with reduced pro-inflammatory activation (P <.007). Conclusion: Our findings suggest that better global self-care was associated with poorer renal function. Performing self-care behaviors such as regular exercise and medication adherence was associated with improved physiological functioning, while restriction of fluid and sodium, and the associated daily weight monitoring were associated with adverse levels of pathophysiological biomarkers. [ABSTRACT FROM AUTHOR]

Previously we have shown that increased expression of renal epithelial sodium channels (ENaC) may contribute to the renal sodium and water retention observed during chronic heart failure (CHF). The goal of this study was to examine whether renal denervation (RDN) changed the expressions of renal sodium transporters ENaC, sodium-hydrogen exchanger-3 proteins (NHE3), and water channel aquaporin 2 (AQP2) in rats with CHF. CHF was produced by left coronary artery ligation in rats. Four weeks after ligation surgery, surgical bilateral RDN was performed. The expression of ENaC, NHE3, and AQP2 in both renal cortex and medulla were measured. As a functional test for ENaC activation, diuretic and natriuretic responses to ENaC inhibitor benzamil were monitored in four groups of rats (Sham, Sham+RDN, CHF, CHF+RDN). Western blot analysis indicated that RDN (1 wk later) significantly reduced protein levels of α-ENaC, β-ENaC, γ-ENaC, and AQP2 in the renal cortex of CHF rats. RDN had no significant effects on the protein expression of kidney NHE3 in both Sham and CHF rats. Immunofluorescence studies of kidney sections confirmed the reduced signaling of ENaC and AQP2 in the CHF+RDN rats compared with the CHF rats. There were increases in diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. RDN reduced the diuretic and natriuretic responses to benzamil in CHF rats. These findings suggest a critical role for renal nerves in the enhanced expression of ENaC and AQP2 and subsequent pathophysiology of renal sodium and water retention associated with CHF. [ABSTRACT FROM AUTHOR]

Aims: Neladenoson bialanate is a partial adenosine A1 receptor agonist with demonstrated beneficial effects on cardiac function in animal models. We aimed to assess the dose-response effect of neladenoson bialanate on cardiac structure and function, clinical outcome, and safety in patients with heart failure (HF) with reduced ejection fraction (HFrEF).Methods and Results: PANTHEON was a dose-finding, phase IIb, randomized, double-blind, placebo-controlled trial conducted in 92 centres in 11 countries including 462 patients with chronic HFrEF, randomized to once daily oral dose of neladenoson bialanate (5, 10, 20, 30, and 40 mg) or placebo. The primary endpoints were change from baseline to 20 weeks in left ventricular ejection fraction (LVEF) (echocardiography) and in N-terminal pro-B-type natriuretic peptide (NT-proBNP). Mean age of the patients was 67 years, 17% were female, mean LVEF was 28%, mean NT-proBNP was 2085 ng/L. After 20 weeks of treatment, there was no dose-effect of neladenoson bialanate on changes in NT-proBNP or LVEF (primary endpoints). No effect of neladenoson bialanate was found on left ventricular volumes, high-sensitivity troponin T, or cardiovascular mortality, HF hospitalization, and urgent visits for HF (secondary endpoints). There was a dose-dependent increase in creatinine and cystatin C, and a dose-dependent decrease in estimated glomerular filtration rate and heart rate.Conclusions: In patients with chronic HFrEF, treatment with neladenoson bialanate was not associated with dose-dependent favourable effects on cardiac structure and function, cardiac risk markers, or clinical outcome but was associated with a dose-dependent decrease in renal function.Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02992288. [ABSTRACT FROM AUTHOR]

Aims: Sodium-glucose co-transporter 2 (SGLT2) inhibition reduces heart failure hospitalizations in patients with diabetes, irrespective of glycaemic control. We examined the effect of SGLT2 inhibition with empagliflozin (EMPA) on cardiac function in non-diabetic rats with left ventricular (LV) dysfunction after myocardial infarction (MI).Methods and Results: Non-diabetic male Sprague-Dawley rats underwent permanent coronary artery ligation to induce MI, or sham surgery. Rats received chow containing EMPA that resulted in an average daily intake of 30 mg/kg/day or control chow, starting before surgery (EMPA-early) or 2 weeks after surgery (EMPA-late). Cardiac function was assessed using echocardiography and histological and molecular markers of cardiac remodelling and metabolism were assessed in the left ventricle. Renal function was assessed in metabolic cages. EMPA increased urine production by two-fold without affecting creatinine clearance and serum electrolytes. EMPA did not influence MI size, but LV ejection fraction (LVEF) was significantly higher in the EMPA-early and EMPA-late treated MI groups compared to the MI group treated with vehicle (LVEF 54%, 52% and 43%, respectively, all P < 0.05). EMPA also attenuated cardiomyocyte hypertrophy, diminished interstitial fibrosis and reduced myocardial oxidative stress. EMPA treatment reduced mitochondrial DNA damage and stimulated mitochondrial biogenesis, which was associated with the normalization of myocardial uptake and oxidation of glucose and fatty acids. EMPA increased circulating ketone levels as well as myocardial expression of the ketone body transporter and two critical ketogenic enzymes, indicating that myocardial utilization of ketone bodies was increased. Together these metabolic changes were associated with an increase in cardiac ATP production.Conclusion: Empagliflozin favourably affects cardiac function and remodelling in non-diabetic rats with LV dysfunction after MI, associated with substantial improvements in cardiac metabolism and cardiac ATP production. Importantly, it did so without renal adverse effects. Our data suggest that EMPA might be of benefit in heart failure patients without diabetes. [ABSTRACT FROM AUTHOR]

• Mannose-binding lectin associated with cardiovascular disease and renal interstitial injury. • We examined associations of mannose-binding lectin with renal function and heart failure. • Mannose-binding lectin was related to both KDIGO stage G3a-G4 and heart failure. • Increased mannose-binding lectin may contribute to the pathogenesis of chronic kidney disease and heart failure. Mannose-binding lectin (MBL) has been associated with cardiovascular disease and its complications, the progression of diabetic nephropathy, and complement-mediated renal interstitial injury. However, the relationship between plasma MBL concentration with both heart failure and renal function is unclear. In this study, we examined associations of plasma MBL with both renal function and heart failure in patients with stable coronary artery disease (CAD). We enrolled 348 consecutive stable CAD patients and used ELISA to evaluate plasma concentrations of MBL. Renal function was classified into KDIGO G1, G2 and G3a-G4 groups according to the eGFR of ≥ 90, 60–89 and 15–59, ml/min/1.73 m2, respectively. Patients with a left ventricular ejection fraction (LVEF) ≤ 40 % were classified to have heart failure. A significant positive association was found between MBL with diabetes mellitus, current smoker, blood urea nitrogen, creatinine, and brain natriuretic peptide, and a significant negative association was found between MBL with eGFR and LVEF. KDIGO stage G3a-G4 and heart failure increased along with tertiles of MBL (p for trend < 0.05). Multivariate analysis showed that compared to the patients with a low MBL concentration, the odds ratios of having KDIGO stage G3a-G4 were 1.89 (1.01–3.55) times and 2.37 (1.25–4.59) times higher for those with medium and high MBL concentrations. Furthermore, compared to the patients with a low MBL concentration, the OR of having heart failure were 1.97 (1.01–3.93) times higher for those with high MBL concentrations. Moreover, multivariate analysis showed an independent association between plasma MBL concentration with both KDIGO stage G3a-G4 and heart failure (LVEF < 40 %). In addition, the effect of MBL on both LVEF and eGFR was confirmed by structural equation model analysis. There are associations between circulating MBL concentration with both heart failure and renal function in stable CAD patients, suggesting that increased plasma MBL may contribute to the pathogenesis of both chronic kidney disease and heart failure. [ABSTRACT FROM AUTHOR]

Background: Current heart failure guidelines recommend target eplerenone dose of 50 mg/day. We have examined the effect of different eplerenone doses based on pre-specified renal function stratification in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).Methods and Results: In EMPHASIS-HF, the target dose of eplerenone/placebo was stratified at randomization according to estimated glomerular filtration rate (eGFR): 50 mg/day if eGFR ≥ 50 mL/min/1.73 m2 and ≤ 25 mg/day if eGFR 30-49 mL/min/1.73 m2 . Patients remained within these dose ranges during the trial (as per stratification). The primary outcome was a composite of heart failure hospitalization or cardiovascular mortality. Eplerenone was superior to placebo within each respective eGFR stratum [eplerenone vs. placebo in the eGFR ≥ 50 mL/min/1.73 m2 stratum: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.45-0.74; and eplerenone vs. placebo in the eGFR 30-49 mL/min/1.73 m2 stratum: HR 0.62, 95% CI 0.49-0.78; Pinteraction  = 0.89]. Despite receiving lower eplerenone doses, patients in the eGFR 30-49 mL/min/1.73 m2 stratum more often had hyperkalaemia, renal failure events, and drug discontinuation.Conclusion: In EMPHASIS-HF the eplerenone dose was stratified according to renal function and the treatment effect was not influenced by renal function: 25 mg/day in patients with eGFR 30-49 mL/min/1.73 m2 was as effective as 50 mg/day in patients with eGFR > =50 mL/min/1.73 m2 . However, patients with impaired renal function experienced more adverse events, despite reveiving lower eplerenone doses. Current guidelines do not recommend tailoring the dose of eplereone according to renal function but the current data suggest they should. [ABSTRACT FROM AUTHOR]

Abstract Background In a recent individual patient data meta-analysis, high-sensitivity troponin T (hs-TnT) emerged as robust predictor of prognosis in stable chronic heart failure (HF). In the same population, we compared the relative predictive performances of hs-TnT, N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), hs-C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) for prognosis. Methods and results 9289 patients (66 ± 12 years, 77% men, 85% LVEF <40%, 60% ischemic HF) were evaluated over a 2.4-year median follow-up. Median eGFR was 58 mL/min/1.73 m2 (interquartile interval 46–70; n = 9220), hs-TnT 16 ng/L (8–20; n = 9289), NT-proBNP 1067 ng/L (433–2470; n = 8845), and hs-CRP 3.3 mg/L (1.4–7.8; n = 7083). In a model including all 3 biomarkers, only hs-TnT and NT-proBNP were independent predictors of all-cause and cardiovascular mortality and cardiovascular hospitalization. hs-TnT was a stronger predictor than NT-proBNP: for example, the risk for all-cause death increased by 54% per doubling of hs-TnT vs. 24% per doubling of NT-proBNP. eGFR showed independent prognostic value from both hs-TnT and NT-proBNP. The best hs-TnT and NT-proBNP cut-offs for the prediction of all-cause death increased progressively with declining renal function (eGFR ≥ 90: hs-TnT 13 ng/L and NT-proBNP 825 ng/L; eGFR < 30: hs-TnT 40 ng/L and NT-proBNP 4608 ng/L). Patient categorization according to these cut-offs effectively stratified patient prognosis across all eGFR classes. Conclusions hs-TnT conveys independent prognostic information from NT-proBNP, while hs-CRP does not. Concomitant assessment of eGFR may further refine risk stratification. Patient classification according to hs-TnT and NT-proBNP cut-offs specific for the eGFR classes holds prognostic significance. Highlights • High-sensitivity troponin T (hs-TnT) is an independent predictor of prognosis in chronic heart failure (HF). • There are hs-TnT and NT-proBNP cut-offs specific for each class of glomerular filtration rate. • Patient classification according to these cut-offs holds prognostic significance. [ABSTRACT FROM AUTHOR]

Background/Aims: The rate of incidence and prevalence of acute kidney injury is increasing due to an increased number of patients with heart failure. Therefore it is very pertinent to early detect the level of renal injuries and to make necessary heart failure predictions. Thus the aim of this study is to determine renal functions and prognosis stratification in chronic heart failure patients and importance of Neutrophil Gelatinase-Associated Lipocalin (NGAL), an early diagnostic marker of acute kidney injury, as well as stratification of cardiovascular risk in heart failure patients. Methods: Data including age, gender, comorbidities and medical history of outpatients and hospitalized patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry comprising three Cardiological Centers in the Czech Republic were collected between 1st October 2014 and 30th November 2015. One-year follow-up data were collected in November 2016 in such a way that all patients had at least one-year data from the time of recruitment, but up to two years to the time of follow-up. One-year data were used for the whole set of patients while data up to 24 months were used with Kaplan-Meier's survival curves to analyse the patients' survival data. Blood samples were collected from the patients and basic parameters were evaluated in order to analyse Neutrophil gelatinase-associated lipocalin (NGAL) and plasma levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) using Lipocalin-2/NGAL Human ELISA kit (Bio Vendor, Czechia) and the Cobas E411 NT-proBNP Immunoassay kit (Roche Diagnostics, Indianapolis, IN, USA) respectively. Statistical analysis was further carried out to explain the level of significance of the evaluated parameters using Spearman Correlation, Mann Whitney or Kruskal-Wallis test and log-rank test. Results: Out of 547 patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry with available data on hospitalizations, mortality, biomarkers and one-year follow-up that were recorded, there were 439 males (80.3%) with a median age of 66 years. At least one-month stable patients with left ventricle ejection fraction (LV EF) under 50% were recorded. The etiology of heart failure was ischemic heart disease in 54%, dilated cardiomyopathy in 40% and others in 6%. 69% patients were in New York Heart Association functional class II. There were 76 events (13.9%; all-cause mortality, acute heart failure hospitalization, left ventricle assist device implantation and orthotopic heart transplant) in the first 365 days of follow-up. The area under the receiver operating characteristic curve was higher for NT-proBNP (0.77) than the creatinine (0.57), NGAL (0.55) or creatinine clearance (0.54). In multivariable analyses, NT-proBNP (P= 0.001) and NGAL (P = 0.004) were significant predictors of events. Subjects with NT-proBNP and NGAL above the cut off value (NT-proBNP 1,121 pg/ml, NGAL 80 ng/ml) survived without any event in 55.7%, subjects with NT-proBNP and NGAL under the cut off value survived without any event in 90.5%, after two years (P = 0.001). Conclusion: The findings of the study showed that NGAL associated with NT-proBNP was a stronger predictor of the primary endpoint than NGAL or NT-proBNP alone. The level of NGAL was rising in hypertension, ischemia, anemia, hypoalbuminemia, diabetes or arrhythmias. [ABSTRACT FROM AUTHOR]

The mechanisms of cardiovascular and renal protection observed in clinical trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) are incompletely understood and likely multifactorial, including natriuretic, diuretic, and antihypertensive effects, glomerular pressure reduction, and lowering of plasma and interstitial fluid volume. To quantitatively evaluate the contribution of proposed SGLT2i mechanisms of action on changes in renal hemodynamics and volume status, we coupled a mathematical model of renal function and volume homeostasis with clinical data in healthy subjects administered 10 mg of dapagliflozin once daily. The minimum set of mechanisms necessary to reproduce observed clinical responses (urinary sodium and water excretion, serum creatinine and sodium) was determined, and important unobserved physiological variables (glomerular pressure, blood and interstitial fluid volume) were then simulated. We further simulated the response to SGLT2i in diabetic virtual patients with and without renal impairment. Multiple mechanisms were required to explain the observed response: 1) direct inhibition of sodium and glucose reabsorption through SGLT2, 2) SGLT2-driven inhibition of Na+/H+ exchanger 3 sodium reabsorption, and 3) osmotic diuresis coupled with peripheral sodium storage. The model also showed that the consequences of these mechanisms include lowering of glomerular pressure, reduction of blood and interstitial fluid volume, and mild blood pressure reduction, in agreement with clinical observations. The simulations suggest that these effects are more significant in diabetic patients than healthy subjects and that while glucose excretion may diminish with renal impairment, improvements in glomerular pressure and blood volume are not diminished at lower glomerular filtration rate, suggesting that cardiorenal benefits of SGLT2i may be sustained in renally impaired patients. [ABSTRACT FROM AUTHOR]

Abstract Patients with type 2 diabetes mellitus have an increased risk for the development of cardiac and other vascular events, heart failure (HF), and decline in renal function. After several large cardiovascular outcome trials with mostly neutral results, 2 studies of the sodium–glucose co-transporter 2 inhibitors (SGLT2is), empagliflozin and canagliflozin, reported favorable effects on the primary endpoint, a composite of myocardial infarction, stroke, and cardiovascular death. In addition, reductions of hospitalizations for HF were observed; in the case of empagliflozin, reductions in both cardiovascular mortality and total mortality occurred. These findings prompted several analyses to elucidate the mechanisms of action of SGLT2is and have initiated several large clinical trials in patients with HF without type 2 diabetes mellitus. This review summarizes known and possible mechanisms that contribute to these salutary effects of SGLT2is. Also discussed is the interplay between cardiac and renal function, as well as safety issues associated with this class of drugs. Central Illustration [ABSTRACT FROM AUTHOR]

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: • Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin are recommended for the prevention of HF hospitalization in patients with type 2 diabetes mellitus and established cardiovascular disease or at high cardiovascular risk. • Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalization and cardiovascular death in symptomatic patients with HF and reduced ejection fraction already receiving guideline-directed medical therapy regardless of the presence of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Tolvaptan has been gradually spread to use as a potent diuretic for congestive heart failure in the limited country. However, the response to this aquaretic drug still is unpredictable. A total of 92 patients urgently hospitalized due to congestive heart failure and treated with tolvaptan in addition to standard treatment was retrospectively analyzed. Responder of tolvaptan treatment was defined as a patient with peak negative fluid balance greater than 500 mL/day, and clinical profiles were compared between 76 responders and 16 non-responders. Responders started to increase daily urine volume (UV) from Day 1 through Day 3. In contrast, non-responders showed no significant increase in daily UV from the baseline up to Day 5. Time between admission and tolvaptan administration was shorter in responders, even without statistical significance (3.3 vs. 4.6 days, p = 0.053). Multivariate analysis revealed that blood urea nitrogen (BUN) [cutoff: 34 mg/dL, odds ratio (OR) 9.0, 95% confidence interval (CI) 1.42-57.3, p < 0.01] and plasma renin activity (PRA) (cutoff: 4.7 ng/mL/h, OR 6.1, 95% CI 1.01-36.4, p < 0.01) at baseline were independent predictors for tolvaptan responsiveness. It suggests that renal perfusion may affect tolvaptan-induced UV. Finally, durations of stay in intensive care unit and total hospitalization were significantly shorter in responders (median: 6.0 vs. 13.0 days, p = 0.022; 15.0 vs. 25.0 days, p = 0.016, respectively). Responders of tolvaptan have lower BUN and renin activity at baseline, and shorten hospitalization period.Trial RegistrationThe study was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) with the identifier UMIN000023594. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024988 [ABSTRACT FROM AUTHOR]

Patients with chronic heart failure (CHF) are often accompanied with varying degrees of renal diseases. The purpose of this study was to identify rs37369 polymorphism of AGXT2 specific to the renal function of CHF patients. A total of 1012 southern Chinese participants, including 487 CHF patients without history of renal diseases and 525 healthy volunteers, were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes of AGXT2 rs37369 polymorphism. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected to indicate the renal function of the participants. BUN level was significantly higher in CHF patients without history of renal diseases compared with healthy volunteers ( p = 0.000). And the similar result was also obtained for SCr ( p = 0.000). Besides, our results indicated that the level of BUN correlated significantly with SCr in both the CHF patients without renal diseases ( r = 0.4533, p < 0.0001) and volunteers ( r = 0.2489, p < 0.0001). Furthermore, we found that the AGXT2 rs37369 polymorphism could significantly affect the level of BUN in CHF patients without history of renal diseases ( p = 0.036, AA + AG vs GG). Patients with rs37369 GG genotype showed a significantly reduced level of BUN compared to those with the AA genotype ( p = 0.024), and the significant difference was still observed in the smokers of CHF patients without renal diseases ( p = 0.023). In conclusion, we found that CHF might induce the impairment of kidney and cause deterioration of renal function. AGXT2 rs37369 polymorphism might affect the renal function of CHF patients free from renal diseases, especially in patients with cigarette smoking. [ABSTRACT FROM AUTHOR]

In patients with congestive heart failure and renal dysfunction, high dose of diuretics are necessary to improve congestion, which may progress to renal dysfunction. We examined the efficacy of tolvaptan with reduction of loop diuretics to improve renal function in patients with congestive heart failure and renal dysfunction. We conducted a multicenter, prospective, randomized study in 44 patients with congestive heart failure and renal dysfunction (serum creatinine concentration ≥1.1 mg/dl) treated with conventional diuretics. Patients were randomly divided into two groups: tolvaptan (15 mg) with a fixed dose of diuretics or with reducing to a half-dose of diuretics for 7-14 consecutive days. We examined the change of urine volume, body weight, serum creatinine and electrolyte concentrations in each group. Both groups demonstrated significant urine volume increase (724 ± 176 ml/day in the fixed-dose group and 736 ± 114 ml/day in the half-dose group) and body weight reduction (1.6 ± 1.5 kg and 1.6 ± 1.9 kg, respectively) from baseline, with no differences between the two groups. Serum creatinine concentration was significantly increased in the fixed-dose group (from 1.60 ± 0.47 to 1.74 ± 0.66 mg/dl, p = 0.03) and decreased in the half-dose group (from 1.98 ± 0.91 to 1.91 ± 0.97 mg/dl, p = 0.10). So the mean changes in serum creatinine concentration from baseline significantly differed between the two groups (0.14 ± 0.08 mg/dl in the fixed-dose group and −0.07 ± 0.19 mg/dl in the half-dose group, p = 0.006). The administration of tolvaptan with reduction of loop diuretics was clinically effective to ameliorate congestion with improving renal function in patients with congestive heart failure and renal dysfunction. [ABSTRACT FROM AUTHOR]

Background Most heart failure with preserved ejection fraction (HFpEF) patients, at some point, present to an emergency department with typical symptoms of volume overload. Clinically, most respond well to standard diuretic therapy, sometimes at the cost of renal function. The study sought to define the prognostic significance of fluid status versus renal function in patients with HFpEF. Methods One hundred sixty-two consecutive patients with HFpEF were enrolled in our prospective registry. Twelve patients with clinically overt decompensation were excluded. Fluid status at baseline was determined by bioelectrical impedance spectroscopy. The primary outcome measure was a combined end point consisting of hospitalization for heart failure and/or death for cardiac reason. Results Mean age was 74.4 ± 8.4 years. Ninety-one (61%) patients were hypo- or normovolemic (relative fluid overload [Rel. FO] − 0.7 ± 5.7%) while 59 (39%) patients presented with fluid overload (Rel. FO 11.5 ± 2.7%). During a median follow-up of 24.3 months (interquartile range: 19.8–33.2), 34% of patients reached the combined end point. Multivariate Cox hazard analysis identified fluid overload (hazard ratio: 3.09; 95% confidence interval: 1.68–5.68; p < 0.001) as an independent predictor of adverse outcome. Patients with fluid overload and normal renal function showed a worse event-free survival compared to the subgroup with normohydration and impaired renal function (log-rank: p = 0.042). Conclusion HFpEF patients with measurable fluid overload face a dismal prognosis as compared to euvolemic patients. Our data, while preliminary, suggest that patients with fluid overload may face a better outcome under continued fluid removal irrespective of changes in eGFR . [ABSTRACT FROM AUTHOR]

The first works focused on the improvement of the care of the chronic herat failure patients were published about 30 years ago. The new Guidelines for the diagnosis and treatment of acute and chronic heart failure were published in 2016 and have brought new information about heart failure (definition of heart failure, influence of ejection fraction of left ventricle) against the Guidelines from 2012. Prevalence of heart failure is about 1-2 % in adult population in developed countries and increases according to the age (more than 10 % in age over 70 years). In chronic heart failure patients is very often polymorbidity, but they are also treated with inadequate doses of medication, poorly educated and also their compliance to the recommended treatment regimen in unsatisfactory. For future years is to be expected increase incidence and prevalence of heart failure, according to the age and also the new therapeutic options. [ABSTRACT FROM AUTHOR]

Aims The clinical implication of the inferior vena cava collapsibility index ( IVCCI) has not been well evaluated in patients with various cardiovascular diseases. Method and results The relationships between clinical characteristics and echocardiographic indicators of the systemic intravascular volume status [ IVCCI; the ratio of the early transmitral and early myocardial diastolic velocities (E/Em)] were evaluated at baseline, and the clinical status during follow-up was compared across the IVCCI levels. Among 1166 patients (mean age=63.8±13.4 years), 934, 171, and 61 had high (≥50%), intermediate (25%-50%), and low (<25%) IVCCIs, respectively. Age-, sex-, and body mass index-adjusted serum creatinine ( sCr) levels were highest in patients with low IVCCI ( P=.002) and E/Em >15 ( P<.001). During follow-up (1108±463 days), 67 patients died, and 38 of these deaths were cardiovascular related. Age, body mass index, heart failure ( HF), sCr levels, and a low IVCCI (vs high IVCCI: hazard ratio [ HR]=3.193, 95% confidence interval [ CI]=1.297-7.857, P=.012) were associated with all-cause mortality in multivariable analysis. HF, diuretic use, and a low IVCCI (vs high IVCCI: HR=4.428, 95% CI=1.406-13.104, P=.007) were significantly associated with cardiovascular mortality. Conclusion A low IVCCI was significantly associated with reduced renal function and was an independent risk factor for adverse outcomes, regardless of underlying cardiovascular disease and renal function. [ABSTRACT FROM AUTHOR]

Although intravenous diuretics have been mainstay drugs in patients with acute heart failure (AHF), they have been suggested to have some deleterious effects on prognosis. We postulated that renal function may modify their deleterious effects in AHF patients. The study population consisted of 1094 AHF patients from three hospitals. Renal dysfunction (RD) was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m on admission, and the cohort was divided into a high-dose furosemide (≥100 mg/48 h) and low-dose furosemide group according to the amount of intravenous furosemide used within 48 h from admission. In the whole cohort, in-hospital mortality rate was higher in the high-dose furosemide group than the low-dose furosemide group (12.5 vs. 6.6 %, respectively, P = 0.001). However, this difference in the in-hospital mortality rates was significant only in the RD subgroup (15.6 vs. 7.0 %, respectively, P < 0.001), and not in the non-RD subgroup (2.5 vs. 5.9 %, respectively, P = 0.384). Propensity score-matched analysis was performed to evaluate the impact of high-dose furosemide on prognosis. After propensity score matching, high-dose furosemide was not associated with in-hospital mortality (OR 1.25, 95 % CI 0.73-2.16, P = 0.408). However, there was a qualitative difference in OR for in-hospital mortality between AHF with RD (OR 1.77, 95 % CI 0.96-3.28, P = 0.068) and without RD (OR 0.23, 95 % CI 0.05-1.10, P = 0.064), and there was a significant interaction between eGFR and prognostic impact of high-dose furosemide ( P for OR interaction = 0.013). An inverse relationship was observed between eGFR and OR for in-hospital death in the group treated with high-dose furosemide (decreasing OR with better eGFR). The deleterious effect of diuretics was significantly modified with renal function in AHF. This association may be one reason for poorer prognosis of AHF patients complicated with renal impairment. [ABSTRACT FROM AUTHOR]

Background B-type natriuretic peptide (BNP) and echocardiography are potentially useful adjunct to guide management of patients with chronic heart failure (HF).Thus, the aim of this retrospective, multicenter study was to compare outcomes and renal function in outpatients with chronic HF with reduced ejection fraction (HFrEF) who underwent an echo and BNP guided or a clinically driven protocol for follow-up. Methods and results In 1137 consecutive outpatients, management was guided according to echo-Doppler signs of elevated left ventricular filling pressure and BNP levels conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group in 570 (mean EF = 30%), while management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department in 567 (mean EF = 33%). Propensity score, matching several confounding baseline variables, was used to match pairs based on treatment strategy. The median follow-up was 37.4 months. After propensity matching, a lower incidence of death (HR 0.45, 95%CI: 0.30–0.67, p < 0.0001), and death or worsening renal function (HR 0.49, 95%CI 0.36–0.67, p < 0.0001) was apparent in echo-BNP-guided group compared to clinically-guided group. Worsening of renal function (≥ 0.3 mg/dl increase in serum creatinine) was observed in 9.8% of echo-BNP-guided group and in 21.4% of clinical assessed group ( p < 0.0001). The daily dose of loop diuretics did not change in echo-BNP-guided group, while it increased in 65% of patients in clinically-guided group ( p < 0.0001). Conclusions Echo and BNP guided management may improve the outcome and reduce worsening of renal function in outpatients with chronic HFrEF. [ABSTRACT FROM AUTHOR]

Background: Renal impairment is a major risk factor for mortality in various populations. Three formulas are frequently used to assess both glomerular filtration rate (eGFR) or creatinine clearance (CrCl) and mortality prediction: body surface area adjusted-Cockcroft-Gault (CG-BSA), Modification of Diet in Renal Disease Study (MDRD4), and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The CKD-EPI is the most accurate eGFR estimator as compared to a "gold-standard"; however, which of the latter is the best formula to assess prognosis remains to be clarified. This study aimed to compare the prognostic value of these formulas in predicting the risk of cardiovascular mortality (CVM) in population-based, cardiovascular risk, heart failure (HF) and post-myocardial infarction (MI) cohorts. Methods: Two previously published cohorts of pooled patient data derived from the partners involved in the HOMAGE-consortium and from four clinical trials - CAPRICORN, EPHESUS, OPTIMAAL and VALIANT - the high risk MI initiative, were used. A total of 54,111 patients were included in the present analysis: 2644 from populationbased cohorts; 20,895 from cardiovascular risk cohorts; 1801 from heart failure cohorts; and 28,771 from postmyocardial infarction cohorts. Participants were patients enrolled in the respective cohorts and trials. The primary outcome was CVM. Results: All formulas were strongly and independently associated with CVM. Lower eGFR/CrCl was associated with increasing CVM rates for values below 60 mL/min/m2. Categorical renal function stages diverged in a more pronounced manner with the CG-BSA formula in all populations (higher χ2 values), with lower stages showing stronger associations. The discriminative improvement driven by the CG-BSA formula was superior to that of MDRD4 and CKD-EPI, but remained low overall (increase in C-index ranging from 0.5 to 2 %) while not statistically significant in population-based cohorts. The integrated discrimination improvement and net reclassification improvement were higher (P < 0.05) for the CG-BSA formula compared to MDRD4 and CKD-EPI in CV risk, HF and post-MI cohorts, but not in population-based cohorts. The CKD-EPI formula was superior overall to MDRD4. Conclusions: The CG-BSA formula was slightly more accurate in predicting CVM in CV risk, HF, and post-MI cohorts (but not in population-based cohorts). However, the CG-BSA discriminative improvement was globally low compared to MDRD4 and especially CKD-EPI, the latter offering the best compromise between renal function estimation and CVM prediction. [ABSTRACT FROM AUTHOR]

Background Heart failure (HF) is a major health problem worldwide with no proven therapy. Low-dose dopamine (LDD) has been applied to patients with HF to enhance diuresis and preserve renal function since the last century. However, the efficacy of LDD in HF has been questioned by several studies recently. The purpose of this meta-analysis is to appraise the effects of the LDD to HF. Methods Relative trials were identified in the PubMed, The Web of Science, OVID EBM Reviews and Cochrane databases, and the relevant papers were examined. Pooled mean difference (MD) and 95% confidence interval (95% CI) were estimated by random effects models. The primary endpoints in our meta-analysis were renal function, determined by blood urea, creatinine levels, eGFR and urine output. Secondary endpoints were rates of all-cause mortality and readmission after treatment. Results Six randomized controlled trials (RCTs) and one retrospective study involving 587 patients were included in this analysis. LDD enhanced eGFR (MD, 7.44; 95% CI, 1.92–12.95; P = 0.008), urine output (SMD, 0.58; 95% CI, 0.15–1.01; P = 0.008) and decrease creatinine levels (MD, − 0.36; 95% CI, − 0.64/− 0.08; P = 0.004), blood urea (MD, − 6.97; 95% CI, − 13.12/− 0.81; P = 0.03). No statistically significant differences in the rates of mortality (RR, 0.86; 95% CI, 0.62–1.20, P = 0.37) and readmission (RR: 0.86; 95% CI 0.47–1.56, P = 0.62) were noted. Conclusions LDD indeed brought benefits in terms of promoting diuresis and preserving renal function for HF patients. It did not demonstrate statistical significance in rates of readmission nor mortality. The efficacy of LDD to HF patients should be confirmed by further large, high quality clinical trials. [ABSTRACT FROM AUTHOR]

Background/objectives Cystatin-C and beta-2-microglobulin may be superior to serum creatinine, blood urea nitrogen (BUN), or estimated glomerular filtration rate (eGFR) in patients hospitalized with heart failure (HF). We compared these renal markers in ambulatory HF patients. Methods We prospectively evaluated the association of baseline renal markers and eGFR (by 4 different formulas) with (1) the composite of death or HF-related hospitalization and (2) rates of hospitalizations and emergency department (ED) visits in 166 outpatients with HF (57.3 ± 11.6 years; 57.2% white, 38.6% black, median left ventricular ejection fraction 27.5% [17.5, 40.0]). Results After a median of 3.9 years, 63 (38.0%) patients met the composite endpoint. There were 458 hospitalizations (177 [38.6%] for HF) and 209 ED visits (51 [24.4%] for HF). Cystatin-based eGFR most consistently predicted (1) the composite endpoint (highest-to-lowest tertile adjusted hazard ratio [HR] 4.92 [95% CI 2.07–11.7; P < 0.001]); and (2) hospitalization rates, including HF hospitalizations (highest-to-lowest tertile, adjusted relative rate 5.24 [95% CI 1.61–17.01; P = 0.006]). Serum creatinine alone was a strong predictor of the composite endpoint (highest-to-lowest tertile, adjusted HR 3.20 [95% CI, 1.51–6.78; P = 0.002]). Only the highest tertile of BUN was associated with rates of ED visits. Conclusions In outpatients with HF, cystatin-based eGFR provides consistent prognostication across outcomes, except ED visits. Serum creatinine is an adequate prognosticator of death or HF hospitalization. [ABSTRACT FROM AUTHOR]