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Congestive nephropathy is an underappreciated manifestation of cardiorenal syndrome and is characterized by a potentially reversible kidney dysfunction caused by a reduced renal venous outflow secondary to right‐sided heart failure or intra‐abdominal hypertension. To date, the histological diagnostic criteria for congestive nephropathy have not been defined. We herein report a case of acute renal dysfunction following cardiac allograft failure and present a review of the relevant literature to elucidate the current understanding of the disease. Our case demonstrated that congestion‐driven nephropathy may be histopathologically characterized by markedly dilated veins and peritubular capillaries, focally accentuated low‐grade acute tubular damage, small areas of interstitial fibrosis, and tubular atrophy on a background of normal glomeruli and predominantly normal tubular cell differentiation. [ABSTRACT FROM AUTHOR]

Aims: Fractional excretion of urea nitrogen (FEUN), used to differentiate the cause of acute kidney injury, has emerged as a useful fluid index in patients with heart failure (HF). We hypothesized that FEUN could be useful in identifying worsening renal function (WRF) associated with poor outcomes in patients with acute HF (AHF). Methods and results: Overall, 1103 patients with AHF (median age, 78 years; male proportion, 60%) were categorized into six groups according to the presence of WRF and FEUN values (low, ≤32.1%; medium, >32.1% and ≤38.0%; and high, >38.0%) at discharge. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). The cut‐off values for low, medium, and high FEUN were based on a previous study. The primary outcome of this study was HF readmission after hospital discharge. During the 1 year follow‐up, 170 HF readmissions occurred. Kaplan–Meier analysis revealed significantly higher HF readmission rates in patients with WRF than in those without WRF (log‐rank test, P < 0.001). Additionally, among patients with WRF, HF readmission rates were lowest in those with medium FEUN values, followed by those with low FEUN values and those with high FEUN values. On multivariable analysis, the presence of WRF with low or high FEUN values was independently associated with increased HF readmission, as compared with the absence of WRF with medium FEUN values. Notably, no association was noted between WRF with medium FEUN values and HF readmission. Conclusions: The prognostic impact of WRF was significantly mediated by the FEUN values and was associated with worse outcomes only when the FEUN values were either low or high. Our study suggests that FEUN can identify prognostically relevant WRF in patients with AHF. [ABSTRACT FROM AUTHOR]

Abstract Aims Fractional excretion of urea nitrogen (FEUN), used to differentiate the cause of acute kidney injury, has emerged as a useful fluid index in patients with heart failure (HF). We hypothesized that FEUN could be useful in identifying worsening renal function (WRF) associated with poor outcomes in patients with acute HF (AHF). Methods and results Overall, 1103 patients with AHF (median age, 78 years; male proportion, 60%) were categorized into six groups according to the presence of WRF and FEUN values (low, ≤32.1%; medium, >32.1% and ≤38.0%; and high, >38.0%) at discharge. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). The cut‐off values for low, medium, and high FEUN were based on a previous study. The primary outcome of this study was HF readmission after hospital discharge. During the 1 year follow‐up, 170 HF readmissions occurred. Kaplan–Meier analysis revealed significantly higher HF readmission rates in patients with WRF than in those without WRF (log‐rank test, P

Abstract Congestive nephropathy is an underappreciated manifestation of cardiorenal syndrome and is characterized by a potentially reversible kidney dysfunction caused by a reduced renal venous outflow secondary to right‐sided heart failure or intra‐abdominal hypertension. To date, the histological diagnostic criteria for congestive nephropathy have not been defined. We herein report a case of acute renal dysfunction following cardiac allograft failure and present a review of the relevant literature to elucidate the current understanding of the disease. Our case demonstrated that congestion‐driven nephropathy may be histopathologically characterized by markedly dilated veins and peritubular capillaries, focally accentuated low‐grade acute tubular damage, small areas of interstitial fibrosis, and tubular atrophy on a background of normal glomeruli and predominantly normal tubular cell differentiation.

AimsKidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF).Methods and resultsWe evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in-hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One-hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16-1.28, 95% confidence interval [CI] 1.00-1.55) and lower diastolic blood pressure (OR 0.97-0.98, 95% CI 0.96-0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0-2.2). WRF across definitions was not associated with a higher odds of adverse in-hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome.ConclusionsAdmission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in-hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events.

Abstract Aims The prognostic value of ‘high dose’ loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). Methods and results All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into ‘low dose’, ‘intermediate dose’, and ‘high dose’ loop diuretics corresponding to furosemide equivalent doses of ≤40, 40–250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N‐terminal pro‐B‐type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for ‘low dose’, ‘intermediate dose’, and ‘high dose’ patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the ‘high dose’ group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six‐fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P 0.05). Conclusions A ‘high dose’ of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre‐HT patients.

Aims: The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). Methods and results: All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40–250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N‐terminal pro‐B‐type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six‐fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P > 0.05). Conclusions: A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre‐HT patients. [ABSTRACT FROM AUTHOR]

Abstract Aims Kidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF). Methods and results We evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase–associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in‐hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One‐hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16–1.28, 95% confidence interval [CI] 1.00–1.55) and lower diastolic blood pressure (OR 0.97–0.98, 95% CI 0.96–0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0–2.2). WRF across definitions was not associated with a higher odds of adverse in‐hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome. Conclusions Admission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in‐hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events.

Abstract Aims Acute heart failure (HF) is associated with muscle mass loss, potentially leading to overestimation of kidney function using serum creatinine‐based estimated glomerular filtration rate (eGFRsCr). Cystatin C‐based eGFR (eGFRCysC) is less muscle mass dependent. Changes in the difference between eGFRCysC and eGFRsCr may reflect muscle mass loss. We investigated the difference between eGFRCysC and eGFRsCr and its association with clinical outcomes in acute HF patients. Methods and results A post hoc analysis was performed in 841 patients enrolled in three trials: Diuretic Optimization Strategy Evaluation (DOSE), Renal Optimization Strategies Evaluation (ROSE), and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS‐HF). Intra‐individual differences between eGFRs (eGFRdiff) were calculated as eGFRCysC–eGFRsCr at serial time points during HF admission. We investigated associations of (i) change in eGFRdiff between baseline and day 3 or 4 with readmission‐free survival up to day 60; (ii) index hospitalization length of stay (LOS) and readmission with eGFRdiff at day 60. eGFRCysC reclassified 40% of samples to more advanced kidney dysfunction. Median eGFRdiff was −4 [−11 to 1.5] mL/min/1.73 m2 at baseline, became more negative during admission and remained significantly different at day 60. The change in eGFRdiff between baseline and day 3 or 4 was associated with readmission‐free survival (adjusted hazard ratio per standard deviation decrease in eGFRdiff: 1.14, P = 0.035). Longer index hospitalization LOS and readmission were associated with more negative eGFRdiff at day 60 (both P ≤ 0.026 in adjusted models). Conclusions In acute HF, a marked difference between eGFRCysC and eGFRsCr is present at baseline, becomes more pronounced during hospitalization, and is sustained at 60 day follow‐up. The change in eGFRdiff during HF admission and eGFRdiff at day 60 are associated with clinical outcomes.

Abstract Aim Patients with advanced heart failure (HF) frequently suffer from renal insufficiency. The impact of durable mechanical circulatory support (MCS) and subsequent heart transplantation (HTx) on kidney function is not well described. Methods and results We studied patients with advanced HF who received durable MCS as bridge to transplantation (BTT) and underwent subsequent HTx at our centre between 1996 and 2018. Glomerular filtration rate (GFR) was measured by 51Cr‐EDTA or iohexol clearance during heart failure work‐up; 3–6 months after MCS; and 1 year after HTx. Chronic kidney disease (CKD) was classified according to KDIGO criteria based on estimated GFR. A total of 88 patients (46 ± 15 years, 84% male) were included, 63% with non‐ischaemic heart disease. The median duration of MCS‐treatment was 172 (IQR 116–311) days, and 81 subjects were alive 1 year after HTx. Measured GFR increased from 54 ± 19 during HF work‐up to 60 ± 16 mL/min/1.73 m2 after MCS (P

Abstract Aims Abnormal renal function is a common feature in patients on heart transplant waiting lists. This study aimed to identify the haemodynamic parameters associated with decreased estimated glomerular filtration rate (eGFR) in patients listed for heart transplantation (HT) and renal function improvement following HT. Methods and results A total of 176 adults (52 years old, 81% men) with available right heart catheterization (RHC) listed in our centre for HT between 2014 and 2019 were studied. Cardiac catheterization measurements were obtained at time of HT listing evaluation. Changes in renal function were assessed between RHC and 6 months after HT. Median eGFR was 63 mL/min/1.73 m2 at time of RHC. Central venous pressure > 10 mmHg was associated with a two‐fold increase in the likelihood of eGFR

Abstract Aims The impact of worsening renal function (WRF) on the prognosis of patients with acute heart failure (AHF) remains controversial. We aimed to identify phenotypically distinct subgroups among individuals with both AHF and WRF using cluster analysis. Methods and results Overall, the data of 483 patients with both AHF and WRF enrolled in the West Tokyo Heart Failure Registry were analysed. Using cluster analysis, we identified three phenotypically distinct subgroups (phenogroups 1, 2, and 3). We assessed the impact of WRF on the prognosis of each phenogroup by comparing the incidence of composite endpoints, including all‐cause death and re‐hospitalization due to heart failure, with those of a propensity score‐matched, non‐WRF control group. Participants in phenogroup 1 (N = 122) were the youngest (69.3 ± 13.7 years), had relatively preserved estimated glomerular filtration rate (eGFR, 70.0 ± 27.7 mL/min/1.73 m2), and reduced left ventricular ejection fraction (LVEF) (41.8 ± 13.7%). Conversely, participants in phenogroup 3 (N = 122) were the oldest (81.7 ± 8.5 years), had the worst eGFR (33.0 ± 20.9 mL/min/1.73 m2), and had preserved LVEF (51.7 ± 14.8%). The characteristics of the participants in phenogroup 2 (N = 239) were between those of phenogroups 1 and 3. The propensity score matching analysis showed that WRF was associated with a higher incidence of composite endpoints in phenogroup 1, whereas this association was not observed in phenogroups 2 and 3. Conclusions Using cluster analysis, we revealed three phenotypically distinct subgroups of patients with both AHF and WRF. WRF was associated with worse clinical outcomes in the subgroup of younger patients with reduced LVEF and preserved renal function.

Aims: Acute heart failure (HF) is associated with muscle mass loss, potentially leading to overestimation of kidney function using serum creatinine‐based estimated glomerular filtration rate (eGFRsCr). Cystatin C‐based eGFR (eGFRCysC) is less muscle mass dependent. Changes in the difference between eGFRCysC and eGFRsCr may reflect muscle mass loss. We investigated the difference between eGFRCysC and eGFRsCr and its association with clinical outcomes in acute HF patients. Methods and results: A post hoc analysis was performed in 841 patients enrolled in three trials: Diuretic Optimization Strategy Evaluation (DOSE), Renal Optimization Strategies Evaluation (ROSE), and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS‐HF). Intra‐individual differences between eGFRs (eGFRdiff) were calculated as eGFRCysC–eGFRsCr at serial time points during HF admission. We investigated associations of (i) change in eGFRdiff between baseline and day 3 or 4 with readmission‐free survival up to day 60; (ii) index hospitalization length of stay (LOS) and readmission with eGFRdiff at day 60. eGFRCysC reclassified 40% of samples to more advanced kidney dysfunction. Median eGFRdiff was −4 [−11 to 1.5] mL/min/1.73 m2 at baseline, became more negative during admission and remained significantly different at day 60. The change in eGFRdiff between baseline and day 3 or 4 was associated with readmission‐free survival (adjusted hazard ratio per standard deviation decrease in eGFRdiff: 1.14, P = 0.035). Longer index hospitalization LOS and readmission were associated with more negative eGFRdiff at day 60 (both P ≤ 0.026 in adjusted models). Conclusions: In acute HF, a marked difference between eGFRCysC and eGFRsCr is present at baseline, becomes more pronounced during hospitalization, and is sustained at 60 day follow‐up. The change in eGFRdiff during HF admission and eGFRdiff at day 60 are associated with clinical outcomes. [ABSTRACT FROM AUTHOR]

Aim: Patients with advanced heart failure (HF) frequently suffer from renal insufficiency. The impact of durable mechanical circulatory support (MCS) and subsequent heart transplantation (HTx) on kidney function is not well described. Methods and results: We studied patients with advanced HF who received durable MCS as bridge to transplantation (BTT) and underwent subsequent HTx at our centre between 1996 and 2018. Glomerular filtration rate (GFR) was measured by 51Cr‐EDTA or iohexol clearance during heart failure work‐up; 3–6 months after MCS; and 1 year after HTx. Chronic kidney disease (CKD) was classified according to KDIGO criteria based on estimated GFR. A total of 88 patients (46 ± 15 years, 84% male) were included, 63% with non‐ischaemic heart disease. The median duration of MCS‐treatment was 172 (IQR 116–311) days, and 81 subjects were alive 1 year after HTx. Measured GFR increased from 54 ± 19 during HF work‐up to 60 ± 16 mL/min/1.73 m2 after MCS (P < 0.001) and displayed a slight but nonsignificant decrease to 57 ± 22 mL/min/1.73 m2 1 year after HTx (P = 0.38). The trajectory of measured GFR did not differ between pulsatile and continuous flow (CF) pumps. Among patients 35–49 years and those who were treated in the most recent era (2012–2018), measured GFR increased following MCS implantation and subsequent HTx. Estimated GFR displayed a similar course as did measured GFR. Conclusions: In patients with advanced heart failure, measured GFR improved after MCS with no difference between pulsatile and CF‐pumps. The total study group showed no further increase in GFR following HTx, but in certain subgroups, including patients aged 35–54 years and those treated during the latest era (2012–2018), renal function appeared to improve after transplant. [ABSTRACT FROM AUTHOR]

Abstract Aims This study aimed to investigate the association between the ‘Shrunken pore syndrome’ (SPS) and risk of death, 30 day rehospitalization, and health‐related quality of life (QoL) in heart failure (HF) patients. SPS is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatin C/eGFRcreatinine ratio. Methods and results A total of 373 patients hospitalized for HF [mean age 74.8 (±12.1) years; 118 (31.6%) women] were retrieved from the HeARt and brain failure inVESTigation trial (HARVEST‐Malmö). Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) formulas were used for estimation of glomerular filtration rate (eGFR). Presence of SPS was defined as eGFRcystatin C ≤ 60% of eGFRcreatinine. In Cox regression multivariate models, associations between SPS, risk of death (median follow‐up time 1.8 years), and risk of 30 day rehospitalization were studied. Associations between SPS and impaired QoL were studied using multivariate logistic regressions. In multivariate models, SPS was associated with all‐cause mortality [124 events; hazard ratio (HR) 1.99; 95% confidence interval (95% CI) 1.23–3.21; P = 0.005] and with 30 day rehospitalization (70 events; HR 1.82; CI 95% 1.04–3.18; P = 0.036). Analyses of QoL, based on a Kansas City Cardiomyopathy Questionnaire overall score

Abstract Aims Cardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine–isosorbide dinitrate (H‐ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof‐of‐concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H‐ISDN compared with standard of care in CRS. Methods and results This multi‐centre, single‐blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR)

Aims: The impact of worsening renal function (WRF) on the prognosis of patients with acute heart failure (AHF) remains controversial. We aimed to identify phenotypically distinct subgroups among individuals with both AHF and WRF using cluster analysis. Methods and results: Overall, the data of 483 patients with both AHF and WRF enrolled in the West Tokyo Heart Failure Registry were analysed. Using cluster analysis, we identified three phenotypically distinct subgroups (phenogroups 1, 2, and 3). We assessed the impact of WRF on the prognosis of each phenogroup by comparing the incidence of composite endpoints, including all‐cause death and re‐hospitalization due to heart failure, with those of a propensity score‐matched, non‐WRF control group. Participants in phenogroup 1 (N = 122) were the youngest (69.3 ± 13.7 years), had relatively preserved estimated glomerular filtration rate (eGFR, 70.0 ± 27.7 mL/min/1.73 m2), and reduced left ventricular ejection fraction (LVEF) (41.8 ± 13.7%). Conversely, participants in phenogroup 3 (N = 122) were the oldest (81.7 ± 8.5 years), had the worst eGFR (33.0 ± 20.9 mL/min/1.73 m2), and had preserved LVEF (51.7 ± 14.8%). The characteristics of the participants in phenogroup 2 (N = 239) were between those of phenogroups 1 and 3. The propensity score matching analysis showed that WRF was associated with a higher incidence of composite endpoints in phenogroup 1, whereas this association was not observed in phenogroups 2 and 3. Conclusions: Using cluster analysis, we revealed three phenotypically distinct subgroups of patients with both AHF and WRF. WRF was associated with worse clinical outcomes in the subgroup of younger patients with reduced LVEF and preserved renal function. [ABSTRACT FROM AUTHOR]

Aims: Abnormal renal function is a common feature in patients on heart transplant waiting lists. This study aimed to identify the haemodynamic parameters associated with decreased estimated glomerular filtration rate (eGFR) in patients listed for heart transplantation (HT) and renal function improvement following HT. Methods and results: A total of 176 adults (52 years old, 81% men) with available right heart catheterization (RHC) listed in our centre for HT between 2014 and 2019 were studied. Cardiac catheterization measurements were obtained at time of HT listing evaluation. Changes in renal function were assessed between RHC and 6 months after HT. Median eGFR was 63 mL/min/1.73 m2 at time of RHC. Central venous pressure > 10 mmHg was associated with a two‐fold increase in the likelihood of eGFR < 60 mL/min/1.73 m2 at time of RHC (adjusted odd ratio, 2.2; 95% confidence interval, 1.1–4.7; P = 0.04). In the 134 patients (76%) who underwent HT during follow‐up, eGFR decreased by 7.9 ± 29.7 mL/min/1.73 m2 from RHC to 6 months after HT. In these patients, low cardiac index (<2.1 L/min/m2) at initial RHC was associated with a (adjusted) 6 month post‐HT eGFR improvement of 12.2 mL/min/1.73 m2 (P = 0.018). Patients with eGFR < 60 mL/min/1.73 m2 and low cardiac index at time of RHC exhibited the greatest eGFR improvement (delta eGFR = 18.3 mL/min/1.73 m2) while patients with eGFR ≥ 60 mL/min/1.73 m2 and normal cardiac index had a marked decrease in eGFR (delta eGFR = −27.7 mL/min/1.73 m2, P < 0.001). Conclusions: Central venous pressure is the main haemodynamic parameter associated with eGFR < 60 mL/min/1.73 m2 in patients listed for HT. Low cardiac index prior to HT is associated with post‐transplant renal function recovery. [ABSTRACT FROM AUTHOR]

Abstract Aims Extracellular vesicles (EVs) are small double‐membrane plasma vesicles that play key roles in cellular crosstalk and mechanisms such as inflammation. The role of EVs in combined organ failure such as cardiorenal syndrome has not been investigated. The aim of this study is to identify EV proteins that are associated with renal dysfunction, heart failure, and their combination in dyspnoeic patients. Methods and results Blood samples were prospectively collected in 404 patients presenting with breathlessness at the emergency department at National University Hospital, Singapore. Renal dysfunction was defined as estimated glomerular filtration rate

Aims This study aimed to investigate the association between the ‘Shrunken pore syndrome’ (SPS) and risk of death, 30 day rehospitalization, and health-related quality of life (QoL) in heart failure (HF) patients. SPS is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatin C/eGFRcreatinine ratio. Methods and results A total of 373 patients hospitalized for HF [mean age 74.8 (±12.1) years; 118 (31.6%) women] were retrieved from the HeARt and brain failure inVESTigation trial (HARVEST-Malmö). Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used for estimation of glomerular filtration rate (eGFR). Presence of SPS was defined as eGFRcystatin C ≤ 60% of eGFRcreatinine. In Cox regression multivariate models, associations between SPS, risk of death (median follow-up time 1.8 years), and risk of 30 day rehospitalization were studied. Associations between SPS and impaired QoL were studied using multivariate logistic regressions. In multivariate models, SPS was associated with all-cause mortality [124 events; hazard ratio (HR) 1.99; 95% confidence interval (95% CI) 1.23–3.21; P = 0.005] and with 30 day rehospitalization (70 events; HR 1.82; CI 95% 1.04–3.18; P = 0.036). Analyses of QoL, based on a Kansas City Cardiomyopathy Questionnaire overall score < 50, revealed that SPS was associated with higher risk of low health-related QoL (odds ratios 2.15; CI 95% 1.03–4.49; P = 0.042).Conclusions The results of this observational study show for the first time an association between SPS and poor prognosis in HF. Further studies are needed to confirm the results in HF cohorts and experimental settings to identify pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Aims: Cardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine–isosorbide dinitrate (H‐ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof‐of‐concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H‐ISDN compared with standard of care in CRS. Methods and results: This multi‐centre, single‐blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2]. The primary outcome was 6 min walk test (6MWT) distance measured at 6 months. Secondary outcomes included study feasibility; efficacy outcomes which included renal, cardiac, and endothelial functions, health‐related quality of life using Short Form‐36, clinical outcomes; and adverse events. Forty‐four patients [71 ± 10 years; 75% male; median (inter‐quartile range) N‐terminal prohormone brain natriuretic peptide 1346 (481–2272) pg/mL] with CRS (left ventricular ejection fraction 42 ± 12% and eGFR 46 ± 15 ml/min/1.73 m2) were randomized into two equal groups. Of these, 39 (89%) had hypertension, 27 (61%) had diabetes mellitus, and 17 (39%) had atrial fibrillation. Six (27%) discontinued H‐ISDN owing to intolerance and poor compliance. There was a trend towards improved 6MWT distance with H‐ISDN compared with standard of care at 6 months (mean difference 27 m; 95% CI, −12 to 66), with little differences in secondary efficacy outcomes. Giddiness and hypotension occurred more frequently with H‐ISDN, but HF hospitalizations and mortality were less. Conclusions: Our pilot study does not support the addition of H‐ISDN on top of standard medical therapy to improve exercise capacity in patients with CRS. [ABSTRACT FROM AUTHOR]

Aims: Extracellular vesicles (EVs) are small double‐membrane plasma vesicles that play key roles in cellular crosstalk and mechanisms such as inflammation. The role of EVs in combined organ failure such as cardiorenal syndrome has not been investigated. The aim of this study is to identify EV proteins that are associated with renal dysfunction, heart failure, and their combination in dyspnoeic patients. Methods and results: Blood samples were prospectively collected in 404 patients presenting with breathlessness at the emergency department at National University Hospital, Singapore. Renal dysfunction was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2. The presence of heart failure was independently adjudicated by two clinicians on the basis of the criteria of the European Society of Cardiology guidelines. Protein levels of SerpinG1, SerpinF2, Cystatin C, and CD14 were measured with a quantitative immune assay within three EV sub‐fractions and in plasma and were tested for their associations with renal dysfunction, heart failure, and the concurrence of both conditions using multinomial regression analysis, thereby correcting for confounders such as age, gender, ethnicity, and co‐morbidities. Renal dysfunction was found in 92 patients (23%), while heart failure was present in 141 (35%). In total, 58 patients (14%) were diagnosed with both renal dysfunction and heart failure. Regression analysis showed that Cystatin C was associated with renal dysfunction, heart failure, and their combination in all three EV sub‐fractions and in plasma. CD14 was associated with both renal dysfunction and the combined renal dysfunction and heart failure in all EV sub‐fractions, and with presence of heart failure in the high density lipoprotein sub‐fraction. SerpinG1 and SerpinF2 were associated with heart failure in, respectively, two and one out of three EV sub‐fractions and in plasma, but not with renal dysfunction. Conclusions: We provide the first data showing that Cystatin C and CD14 in circulating EVs are associated with both renal dysfunction and heart failure in patients presenting with acute dyspnoea. This suggests that EV proteins may be involved in the combined organ failure of the cardiorenal syndrome and may represent possible targets for prevention or treatment. [ABSTRACT FROM AUTHOR]

Aims: Each episode of acute decompensated heart failure (HF) incrementally adds to mortality. Peritoneal dialysis (PD) offers an alternative therapeutic option in refractory HF and reduces the incidence of decompensation episodes. The objective of this study was to determine the efficacy of PD, in terms of functional status, surrogate endpoints, rate of hospitalizations, and mortality. Methods and results: This study is based on the registry of the German Society of Nephrology, involving 159 patients receiving PD treatment due to refractory HF between January 2010 and December 2014. Body weight was reduced by PD (82.2 ± 14.9 to 78.4 ± 14.8 kg, P < 0.001), and significant improvements in New York Heart Association functional class (3.38 ± 0.55 to 2.85 ± 0.49, P < 0.001) were found already after 3 months. Left ventricular ejection fraction did not change (31.5 ± 13.8 to 34.0 ± 15.7%, P = 0.175). C‐reactive protein improved with PD treatment (33.7 ± 52.6 to 17.1 ± 26.3 mg/L, P = 0.004). Blood urea nitrogen/creatinine ratio decreased significantly (148.7 ± 68.3 to 106.7 ± 44.8 mg/dL, P < 0.001). Hospitalization rates decreased significantly (total number 2.86 ± 1.88 to 1.90 ± 1.78, P = 0.001, and 39.2 ± 30.7 to 27.1 ± 25.2 days, P = 0.004). One year mortality was 39.6% in end‐stage HF patients treated with PD. Conclusions: Peritoneal dialysis offers an additional therapeutic option in end‐stage HF and is associated with improved New York Heart Association classification and reduced hospitalization. Although PD treatment was associated with various benefits, further studies are necessary to identify which patients benefit the most from PD. [ABSTRACT FROM AUTHOR]

Aims: This study aims to evaluate the incidence and impact of cardiorenal anaemia syndrome (CRAS) on all‐cause mortality in acute heart failure (AHF) patients stratified by left ventricular ejection fraction (LVEF) status in the Middle East. Methods and results: Data were analysed from 4934 consecutive patients admitted to 47 hospitals in seven Middle Eastern countries (Saudi Arabia, Oman, Yemen, Kuwait, United Arab Emirates, Qatar, and Bahrain) with AHF from February to November 2012. CRAS was defined as AHF with estimated glomerular filtration rate of <60 mL/min and low haemoglobin (<13 g/dL for men or <12 g/dL for women). Analyses were performed using univariate and multivariate statistical techniques. The overall mean age of the cohort was 59 ± 15 years, 62% (n = 3081) were men, and 27% (n = 1319) had CRAS. Co‐morbid conditions were common including hypertension (n = 3014; 61%), coronary artery disease (n = 2971; 60%), and diabetes mellitus (n = 2449; 50%). A total of 79% (n = 3576) of the patients had AHF with reduced ejection fraction (HFrEF) (LVEF < 50%). CRAS patients were associated with major bleeding (1.29% vs. 0.6%; P = 0.017), blood transfusion (10.1% vs. 3.0%; P < 0.001), higher re‐admission rate for AHF at 3 months' follow‐up (27.6% vs. 18.8%; P < 0.001) and at 12 months' follow‐up (34.3% vs. 26.2%; P < 0.001). Multivariate logistic regression demonstrated that patients with CRAS were associated with higher odds of all‐cause mortality during hospital admission [adjusted odds ratio (aOR), 2.10; 95% confidence interval (CI): 1.34–3.31; P = 0.001], at 3 months' follow‐up (aOR, 1.48; 95% CI: 1.07–2.06; P = 0.018), and at 12 months' follow‐up (aOR, 1.45; 95% CI: 1.12–1.87; P = 0.004). Stratified analyses showed that CRAS patients with HFrEF were associated with higher odds of all‐cause mortality during hospital admission (aOR, 2.03; 95% CI: 1.20–3.45; P = 0.009) and at 12 months' follow‐up (aOR, 1.42; 95% CI: 1.06–1.89; P = 0.019) but not at 3 months' follow‐up (aOR, 1.43; 95% CI: 0.98–2.09; P = 0.063). However, in AHF patients with preserved ejection fraction (LVEF ≥ 50%), CRAS was not associated with higher odds of all‐cause mortality not only during hospital admission (aOR, 2.15; 95% CI: 0.84–5.55; P = 0.113) but also at 3 months' follow‐up (aOR, 1.87; 95% CI: 0.93–3.76; P = 0.078) and at 12 months' follow‐up (aOR, 1.59; 95% CI: 0.91–2.76; P = 0.101). Conclusions: The incidence of CRAS was 27%. CRAS was associated with higher odds of all‐cause mortality in AHF patients in the Middle East, especially in those with HFrEF. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Acute cardiorenal syndrome (CRS) with and without consideration of the volume state was assessed with regard to inflammatory parameters. Methods and results: Blood samples from patients with acute CRS (Ronco type 1 or 3, Group 1, n = 15), end‐stage renal disease (Group 2, n = 12), hypertension (Group 3, n = 15), and, in a second cohort, with acute CRS and hypervolemia (Group 4, n = 9) and hypertension (Group 5, n = 10) were analysed with regard to lipopolysaccharide‐binding protein (LBP), interleukins (ILs), and monocyte function (flow cytometry) both on admission (all groups) and on discharge (Groups 1 and 4). By discharge, one Group 1 patient died. LBP (ANOVA for Groups 1–3: P = 0.001) and IL‐6 (Kruskal–Wallis for Groups 1–3: P < 0.0001) were higher in Group 1 (LBP: 11.7 ± 2.0 μg/mL; IL‐6: 15.0 ± 6.1 pg/mL) and in Group 2 (LBP: 10.4 ± 1.4 μg/mL; IL‐6: 14.6 ± 3.8 pg/mL) than in Group 3 (LBP: 5.8 ± 0.4 μg/mL; IL‐6: 1.8 ± 0.4 pg/mL). In a direct comparison, the proportion of activated monocytes (CD14 and CD16 positive) was higher in Group 1 (6.9% ± 0.7%) vs. Group 3 (5.1% ± 0.6%; P = 0.018). Group 4 patients had higher IL‐6 plasma levels (34.2 ± 10.1 pg/mL) than Group 1 patients (15.0 ± 6.1 pg/mL; P = 0.03). All other findings obtained in CRS groups (Groups 1 and 4) were comparable. Conclusions: In acute CRS, a state of systemic inflammation was found, which is comparable with the end‐stage renal disease situation. In comparison with hypertensive controls, a monocytic activation was found in acute CRS regardless of volume state. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion. Methods and results: A retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function. Conclusions: An acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction. [ABSTRACT FROM AUTHOR]

Background: Acute heart failure (AHF) is a leading cause of death in critically ill patients and is often accompanied by significant renal dysfunction. Few data exist on the predictive value of measures of renal dysfunction in large cohorts of patients hospitalized for AHF., Methods: Six hundred and eighteen patients hospitalized for AHF (300 male, aged 73.3 ± 10.3 years, 73% New York Heart Association Class 4, mean hospital length of stay 12.9 ± 7.7 days, 97% non-ischaemic AHF) were included in a retrospective single-centre data analysis. Echocardiographic data, serum creatinine/urea levels, estimated glomerular filtration rate (eGFR), and clinical/laboratory markers were recorded. Mean follow-up time was 2.9 ± 2.1 years. All-cause mortality was recorded, and univariate/multivariate analyses were performed., Results: Normal renal function defined as eGFR > 90 mL/min/1.73 m 2 was noted in only 3% of AHF patients at baseline. A significant correlation of left ventricular ejection fraction with serum creatinine levels and eGFR (all P  < 0.002) was noted. All-cause mortality rates were 12% (90 days) and 40% (at 2 years), respectively. In a multivariate model, increased age, higher New York Heart Association class at admission, higher total cholesterol levels, and lower eGFR independently predicted death. Patients with baseline eGFR < 30 mL/min/1.73 m 2 had an exceptionally high risk of death (odds ratio 2.80, 95% confidence interval 1.52-5.15, P  = 0.001)., Conclusions: In a large cohort of patients with mostly non-ischaemic AHF, enhanced serum creatinine levels and reduced eGFR independently predict death. It appears that patients with eGFR < 30 mL/min/1.73 m 2 have poorest survival rates. Our data add to mounting data indicating that impaired renal function is an important risk factor for non-survival in patients hospitalized for AHF.