Worse Renal Function Research Articles

Relationship between clinical congestion and worsening renal function after intravenous initiation of furosemide in patients with acute heart failure.

To investigate if worsening renal function (WRF) appearing in some patients with acute heart failure (AHF) after intravenous furosemide initiation is influenced by severity of congestion. We conducted a retrospective secondary analysis of consecutive patients diagnosed with AHF and prospectively included in 10 Spanish emergency departments (EDs) for whom serum creatinine at ED arrival and after 2-7days of intravenous furosemide initiation were available. Congestion was clinically evaluated by identification of 7 signs/symptoms and by chest X-ray. The outcome was WRF, defined as a delta-creatinine ≥ 0.3mg/dL. Risk of WRF according to congestion was estimated in models adjusted by patient baseline characteristics and vitals at ED arrival, and interaction was also investigated. We included 3027 patients (median age 82years, 56% women), and 657 (21.7%) presented WRF after intravenous furosemide initiation. When signs/symptoms were individually considered, only lower limbs edema was associated with decreased risk of WRF (20.1% vs. 24.8%; OR = 0.76, 95%CI = 0.64-0.91). After adjustment, lower limbs edema persisted inversely associated with WRF (aOR = 0.78, 95%CI = 0.65-0.94), with significant lower risk for patients ≤ 80years and without chronic kidney disease, functional limitation, and hypoxemia (p for interaction 0.01, 0.04, 0.02 and 0.03, respectively). Neither degree of clinical congestion (number of signs/symptoms of congestion) nor radiological congestion in chest X-ray were related to WRF. Worsening renal function was associated with a higher 1-year all-cause mortality (40.1% vs 34.6%; HR = 1.27, 1.10-1.46; aHR = 1.331, 1.151-1.540). In patients with WRF, liver cirrhosis, chronic treatment with loop diuretics and renin-angiotensin system inhibitors, age (> 80years), dementia, heart valve disease and NYHA class III-IV were associated with higher mortality. Intravenous furosemide initiation in patients with AHF without lower limbs edema must be cautious, as they are at increasing risk of developing WRF during the next following days, which in turn is associated with a higher 1-year mortality.

Validation of existing risk scores for worsening renal function in patients with newly diagnosed heart failure: a longitudinal population cohort study

Abstract Background Worsening renal function (WRF) is one of the strongest predictors of outcome in patients with heart failure (HF). The presence of WRF often influences the decision to start, up-titrate, or discontinue disease-modifying HF therapies and is one of the key determinants of suboptimal guideline-directed medical therapy. However, there are now potential cardiovascular pharmacotherapies that have favourable cardiorenal outcomes and reduce the risk of renal decline. It is therefore important to identify patients with HF early in their disease trajectory who are at risk of developing WRF. Purpose The aim of this study was to evaluate two existing WRF risk scores (the Forman risk score and the Basel risk score) in a population-based longitudinal cohort diagnosed with incident HF. Methods Data for individuals with incident HF between 2016 to 2021 were extracted and analysed from the NELSON study conducted in Tayside, Scotland. WRF was defined as a composite event of (i) having two consecutive eGFRs declined by 40% or greater; (ii) having an eGFR < 15mL/min/1.73m2; (iii) initiation of sustained dialysis; (iv) development of end-stage kidney disease; or (v) receiving kidney transplantation. The primary outcome was the occurrence of WRF within 180 days of diagnosis of HF. Among patients hospitalised with HF, in-hospital WRF was also assessed. The area under the curve (AUC) was used to assess the discrimination performance of the two risk scores in individuals with incident HF diagnosed as either in-patients or out-patients. Results 4076 individuals (mean age 72.8 ± 13.2; 58% male; 1081 HFrEF, 646 HFmrEF, 1348 HFpEF, and 1001 HF with unknown ejection fraction (EF)) who were WRF-free at incident HF diagnosis were identified. Of these, 2095 (51.4%) were diagnosed as in-patients, and 1981 (48.6%) were diagnosed as out-patients. 285 (7%) patients developed WRF within 180 days post HF diagnosis. Among the 2,095 HF in-patients, 75 (3.6%) developed WRF before discharge. The Forman risk score had an AUC of 0.618 (95% CI: 0.585 – 0.651) in predicting 180-day WRF, and an AUC of 0.650 (0.587 – 0.713) for in-hospital WRF. The Basel risk score showed similar discriminating performance with an AUC of 0.618 (0.585 – 0.651) for 180-day WRF, and 0.656 (0.593 – 0.719) for in hospital WRF. Conclusions In a contemporary population, conventional risk scores such as the Forman or Basel risk scores have limited discrimination in predicting WRF in incident HF. New models with better discrimination for WRF prediction are therefore needed.

Development and validation of a risk prediction model for worsening renal function in patients with incident heart failure

Abstract Background Worsening renal function (WRF) is one of the strongest predictors of outcome in patients with heart failure (HF). The presence of WRF often influences the decision to start, up-titrate, or discontinue disease modifying HF therapies and is one of the key determinants of suboptimal guideline-directed medical therapy. Existing WRF risk scores were developed in hospitalised HF patients to predict in-hospital WRF. Their performance among incident HF is far from ideal. It is therefore important to develop a new WRF risk prediction model in people with newly diagnosed HF. Purpose This study was to develop and validate a clinical risk prediction model for 180-day WRF post diagnosis of incident HF using data from a population-based longitudinal cohort. Methods We developed and validated a multivariable logistic regression model for WRF in the 180 days post diagnosis of incident HF. Data for individuals with incident HF between 2016 to 2021 were extracted from the NELSON study conducted in Tayside, Scotland. WRF was defined as a composite event of (i) having two consecutive eGFRs declined by 40% or greater; (ii) having an eGFR < 15mL/min/1.73m2; (iii) initiation of sustained dialysis; (iv) development of end-stage kidney disease; (v) receiving kidney transplantation; or (vi) kidney related death. Four candidate models included one model using literature knowledge; one multivariable fractional polynomial (MFP) model; and two stepwise selected models based on either Akaike or Bayesian information criterion (AIC or BIC). Calibration and discrimination were assessed, and performance stability were evaluated using optimism corrected performance via 1000 times bootstrapping. Results 4076 individuals (mean age 72.8 ± 13.2; 58% male; 1081 HF with reduced ejection fraction (HFrEF), 646 with HF with mildly reduced ejection fraction (HFmrEF), 1348 HF with preserved ejection fraction (HFpEF), and 1001 HF with unknown ejection fraction (EF)) who were WRF-free when diagnosed with HF were identified. Of these, 2095 (51.4%) were in-patients, and 1981 (48.6%) were out-patients. 285 (7%) patients developed WRF within 180 days post HF diagnosis. The selected MFP model (comprising 12 predictors, Table 1) showed good calibration (slope = 1.00 [0.86, 1.14]; intercept = 0.0 [-0.13, 0.13]) discrimination (C-statistic = 0.69 [95% CI: 0.65, 0.72]), and stability (optimism corrected: calibration slope = 0.94 [0.80, 1.07]; calibration intercept = -0.14 [-0.50, 0.20]; C-statistic = 0.67 [0.64, 0.71]). Discrimination of the developed model significantly outperformed two existing risk scores (Forman and Basel, both with a C-statistic = 0.62 [0.59 – 0.65]). Conclusions We have shown that the developed model performed better in predicting WRF in individuals with newly diagnosed HF. This could have utility in identifying at risk patients with HF early in the disease trajectory for therapies that can reduce renal decline.Calibration of predicted riskModel estimates for predicting 180d WRF

Randomized trial assessing worsening renal function with dapagliflozin addition in acute decompensated heart failure: ROAD-ADHF trial

Abstract Background Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 inhibitor, has shown to reduce cardiovascular mortality in patients with chronic heart failure.1) In addition, DAPA can enhance diuresis in patients with acute decompensated heart failure (ADHF).2) However, there is little known how early initiation of DAPA might impact the worsening renal function (WRF) when combined with standard decongestive therapy for ADHF. Purpose We aimed to evaluate the impact of initiating DAPA within 24 hours after ADHF admission on WRF, compared to standard decongestive therapy with loop diuretics alone. Methods We enrolled consecutive ADHF patients with a left ventricular ejection fraction (LVEF) less than 50%. The patients were prospectively randomized to either the DAPA group who received DAPA at a dose of 10 mg once daily within 24 hours of admission or the conventional therapy group (CON group) who received loop diuretics alone. Furosemide, loop diuretic, dosage was adjusted by increase or decrease of 10 mg to maintain urine output between a 1-2 mL/kg/hour.3) The primary endpoint was the incidence of WRF, which was defined as an increase in the serum creatinine of ≥ 0.3 mg/dL from baseline within 7 days of admission.4) Additionally, right heart catheterization (RHC) was performed before discharge if the consent was obtained. Results From May 2021 to May 2023, we analyzed a total of 114 patients (56 in the DAPA group and 58 in the CON group). The mean age was 73 years, 35% were female, and the mean LVEF was 32.5%. There was no significant difference in the incidence of WRF between two groups (16.1% in the DAPA group vs. 12.1% in the CON group, P=0.54, Figure 1). The cumulative loop diuretics dose over 7 days was lower in the DAPA group than CON group (184 ± 9.64 mg vs. 214 ± 9.81 mg, P=0.03, Figure 2). RHC before discharge was performed in 54 patients (96.4%) in the DAPA group and in 54 (93.1%) in the CON group. There were no significant differences in the pulmonary artery wedge pressure, pulmonary artery pressure, right atrial pressure, and cardiac index by the thermodilution method or the Fick method between two groups. Conclusion This randomized prospective trial revealed the early initiation of DAPA within 24 hours of admission for ADHF reduced loop diuretic demand without inducing WRF compared to standard decongestive therapy.Figure 1Figure 2

Ventricular assist devices as bridge to heart transplantation: minimally invasive approach with axial pumps vs sternotomy approach with centrifugal pumps: short term results

Abstract Introduction Microaxial flow ventricular assist devices (VADs) with hybrid approach could provide an advantage over centrifugal flow VADs with surgical implantation via median sternotomy as bridge to heart transplantation. Purpose We aimed to compare short-term results in intensive cardiac care unit between both groups. Methods Single-center retrospective registry comparing patients supported with microaxial flow VADs with hybrid approach (Impella 5.0 or 5.5) and surgical centrifugal flow VADs (biventricular or left univentricular CentriMag) as bridge to heart transplantation. Results Including 12 patients (January 2020-March 2022), 7 patients in hybrid approach group (2 patients with Impella 5.0-16,7% and 5 patients with Impella 5.5-41,7%) and 5 pacientes in sternotomy approach group (33.3% biventricular support and 8.3% left ventricular support). In first 48 hours after VAD implantation, worsening of renal function was greater in sternotomy approach group (Cr 2.23±0.88, 1.07±0.58;p=0.021) and there was a trend toward lower hemoglobin values (7.72±0.19, 8.9±1.35;p =0.059), with no differences in other analyzed variables (Table). A trend toward earlier respiratory weaning was observed in hybrid approach group (median 12 vs 48 hours,p=0.067). Sternotomy approach group required more frequent use of continuous renal replacement therapy (60% vs 0%,p=0.045). There were statistically non-significant differences in need for blood products or surgical reinterventions, although percentage of red blood cells transfused in first 48 hours after VAD implantation were lower in hybrid approach group than sternotomy approach group (median 4 (1.5-8) versus 8(2.5-13.5) in sternotomy approach group, p=0.309). The most common complication in sternotomy approach group was tamponade (80%- 4 patients versus 0 patients in hybrid approach) and in hybrid approach group access-related infections (28.57%, 2 patients). Ten patients received a transplant, one died for non-cardiovascular cause, and another underwent the implantation of long term VAD as bridge to transplantation. There were no differences in time from assistance implantation to heart transplantation. The most common complication after heart transplantation was primary graft failure in both groups (40%,2 patients) with no differences in mortality. Conclusions Microxial flow VADs with hybrid approach provide adequate support, with less need for continuous renal replacement therapy and shorter duration of mechanical ventilation after VAD implantation to admission in intensive cardiac care unit, a trend towards lower rates of reintervention due to bleeding was observed. The advantages of minimally invasive approach could increase its use as bridge to heart transplantation compared to VADs with sternotomy approach although small sample size may negatively influence the failure to reach statistical significance, and more studies are necessary to validate our preliminary experience.Variables analyzed 48 hours of admission

Diuretic therapy strategies in decompensated acute heart failure: a systematic review and network metanalysis

Abstract Background Congestion in acute heart failure (AHF) is treated with furosemide, mainly in continuous infusion (furosemide continuous, FC) or iv boluses, and combination of different diuretics. Randomized controlled trials (RCTs) only compared the efficacy and safety of some diuretic strategies with discordant results. Purpose To provide a comprehensive synthesis of the effects of diuretic regimens in AHF. Methods The PubMed, EMBASE, SCOPUS and Cochrane databases were searched for phase III RCTs until July 31st, 2023, evaluating diuretics without any other intervention in patients admitted for AHF, with randomization within 48 hours, no run-in period and/or need of clinical stabilization. The arms assigned to iv boluses or undefined schemas of furosemide/loop diuretic (LD) were grouped together as "furosemide bolus" (FB). The endpoints were weight loss over 24 hours (WL), worsening renal function (WRF), total urine output (tUO) and net urine output (nUO) over 24 hours, hypokalemia (hypoK), and hyponatremia (hypoNa). Heterogeneity was estimated by Thompsons’ I2 statistics, and odds ratios (OR) with 95% confidence intervals were calculated by means of a random-effects model with inverse variance weighting. A leave-one-out analysis, an analysis limited to studies with specified mode of furosemide/LD administration, and an analysis of measures of congestion/decongestion were also carried out. Results Twenty-five RCTs were selected, for a total of 7,095 patients with mean age 69.2±11.1 years and mean LVEF 38.1±12.7%. In subjects treated with furosemide/LD, the mean furosemide equivalent dose was 154.7±53.0 mg/24 hours. Heterogeneity was moderate-to-high (37.3%-66.0% across the study endpoints). FC, FB plus tolvaptan, FB plus sodium-glucose cotransporter inhibitor (SGLT2i), and FB plus thiazide were associated with greater WL than FB (Figure 1A). The combination of FB and thiazide or SGLT2i also portended higher odds of WRF than FB alone, as did the combination of FB and acetazolamide (Figure 1B). tUO was greater with FC (OR 2.77 [1.98-3.88]), FB plus tolvaptan (OR 1.69 [1.22-2.35]), and FB plus SGLT2i (OR 1.95 [1.16-3.28]) than with FB, and nUO was greater with FC (OR 1.50 [1.06-2.13]) and FB plus tolvaptan (OR 1.76 [1.06-2.92]) than with FB. Compared with FB, hypoK was more frequent with FB and thiazide (OR 1.68 [1.29-2.19]), while there was a trend for less hypoK events with FB plus tolvaptan (OR 0.86 [0.69-1.08]). No differences in hypoNa rates were found. Sensitivity analyses were consistent with the main one. Thirteen (52%) and 14 (56%) studies had published information about symptoms and signs of congestion, respectively, and 6 (24%) adopted pre-specified scoring systems. Conclusions FC and most combination diuretic regimens have greater efficacy than FB in promoting WL and diuresis, but at the cost of WRF and hyoK, especially when thiazide is used. Congestion has inconsistently been evaluated in RCTs of diuretic therapy in AHF.

Extracranial systemic embolic events in patients with atrial fibrillation: an individual patient-level meta-analysis of 71 683 patients randomized to NOAC vs warfarin from the COMBINE-AF study

Abstract Background Atrial Fibrillation (AF) poses a significant risk for both ischemic stroke and systemic embolic events (SEE). While the effectiveness of NOAC in preventing ischemic stroke is well-established, there is a lack of detailed analyses specifically characterizing SEE, which constitutes 5- 10% of all embolic events. Purpose To study the clinical characteristics, procedural management, and outcomes by randomized treatment (NOAC vs warfarin) of patients with SEE. Methods Using the COMBINE AF dataset, we conducted an individual patient level meta-analysis of 4 global RCTs (RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48) of warfarin vs. NOAC in AF to assess risks of SEE. Outcomes were analyzed as time-to-first-event using a Cox proportional hazards model. Two authors independently reviewed deaths within 30 days after SEE to identify fatal SEE. Moreover, we independently assessed post SEE procedures to determined relatedness to SEE. Results There were 188 total SEEs, 9 patients (5%) had SEE then developed ischemic stroke; 16 patients (9%) had ischemic stroke then developed SEE; 1 patient had SEE and ischemic stroke simultaneously. Among the 171 patients with SEEs as first event, the median (IQR) age was 75 (68-80) years, 49.7% were female, median (IQR) of BMI was 27.5 (23.5-30.7) kg/m2, mean (SD) of CHADS2-VASC score was 4.7 (1.5). As compared with ischemic stroke (n=1789), SEE patients were more likely to have, PAD (16.5% vs. 5.4%, p <0.001), prior MI (24% vs. 17%, p = 0.02), be Vitamin K Antagonist experienced (57% vs 46%; p=0.007), have worse renal function (median CrCl mL/min; 58 vs 62, p = 0.02) and less likely to have paroxysmal AF (14% vs. 20%, p = 0.05). Of the total of 188 SEEs, 33 (18%) were fatal, 62 (31%) patients underwent surgical or percutaneous intervention (Fig). Standard dose (SD) NOAC significantly reduced the risk of SEE by 29% (95% CI 1-49%, p=0.04) compared with warfarin, However, no significant difference in the risk of SEE was observed between low dose (LD) NOAC and warfarin (Fig). Conclusion Standard dose NOAC was superior to warfarin in preventing SEE in AF patients. This benefit trends to be more pronounced for fatal cases. While SEE were about 1/10th as frequent as ischemic stroke in patients with AF, they were associated with significant morbidity and mortality and often required surgical or percutaneous intervention to restore blood flow.

Clinical outcomes of edoxaban treatment in atrial fibrillation patients with high bleeding risk: insights from the ETNA-AF-China 1-year follow-up

Abstract Background In China and many other countries, anticoagulated atrial fibrillation (AF) patients with high bleeding risk often raises clinical concern; the optimal dose of direct oral anticoagulants (DOACs) preventing stroke/systemic embolic events (SEE) in those population remains unclear. Purpose To assess the effectiveness and safety of edoxaban treatment in Chinese AF patients with high bleeding risk, and to compare 60 mg vs 30 mg dose in this real-world registry. Methods ETNA-AF-China is a prospective, observational study conducted in 89 centres across Chinese Mainland enrolling AF patients receiving edoxaban. This subgroup analysis was based on 1-year follow-up data. Patients were categorized to high bleeding risk group who had a DOAC score ≥6 (age, creatinine clearance, underweight, history of stroke/TIA/SEE, diabetes, hypertension, antiplatelet use, NSAIDs use, history of major/critical bleeding, liver disease) at baseline, or moderate-to-low bleeding risk group meeting criteria of DOAC score <6. The safety, effectiveness, and composite outcomes were reported by comparison between patient subgroups using Cox proportional hazards models. Results Of 4883 patients with 1-year follow-up, 1534 (31.4%, 60 mg: n=518, 30 mg: n=1016) were identified as high bleeding risk and 3349 (68.6%) as moderate-to-low bleeding risk. As expected, patients with high bleeding risk were more often elderly (48.2% ≥80 years), had lower body weight, worse renal function, higher CHA2DS2-VASc score than those with moderate-to-low risk (Figure 1). In both high risk and moderate-to-low risk subgroups, patients receiving 60 mg edoxaban were younger, with better renal function, lower CHA2DS2-VASc score compared with 30 mg. Annualised event rates of major bleeding (HR 2.95, 95%CI 1.62–5.36), all cause death (3.42, 2.29–5.09), CV death (3.27, 1.52–7.04), major adverse cardiac events (MACE, 2.61, 1.69–4.02) and all NCOs were significant higher in patients with high bleeding risk compared with moderate-to-low risk (Figure 2). After multivariable adjustment, edoxaban dose of 60 mg other than 30 mg were associated with significantly lower rates of all cause death (adjusted HR 0.41, 0.18–0.90) and lower trend of NCO3 (0.51, 0.28–0.92) and NCO4 (0.51, 0.30–0.88) by composite of stroke/SEE, major bleeding and death events in high risk subgroup; no significant difference between edoxaban doses and stroke or bleeding outcomes with cumulative low event rates were observed. Conclusion In routine clinical care, AF patients at high bleeding risk faces worse outcomes of death events, MACE, as well as the composite outcomes over moderate-to-low risk patients. Among patients with high bleeding risk, edoxaban use showed effectiveness and safety with overall low incidence, and potential better survival, composite endpoint benefit could be associated with 60mg. Further investigation is ongoing.

Different impact of chronic kidney disease in older patients with heart failure according to frailty

Abstract Introduction Chronic kidney disease (CKD) and frailty are often present in older patients with heart failure (HF). Our aim was to evaluate the impact of CKD and frailty in one-year mortality in a cohort of older (≥75 years) outpatients with HF. Methods Our data come from the FRAGIC study ("Study of the impact of frailty and other geriatric syndromes on the clinical management and prognosis of older outpatients with heart failure"), a multicenter prospective registry conducted in 16 cardiology services in Spain which included ≥75 years outpatients with HF. Results We included 499 patients, mean age 81.4 ± 4.3 years, 38% women. Mean estimated glomerular filtration rate (eGFR) was 52.1±17.5 ml/min/1.72 m2. Patients were classified in three groups: eGFR ≥60 ml/min/1.72m2 (normal: 182 patients, 36%), eGFR 30-59 ml/min/1.72m2 (moderately impaired: 261 patients, 52.7%), and eGFR < 30 ml/min/1.72m2 (severely impaired: 56 patients, 11.3%). Patients with severe renal dysfunction were older, more often female, and presented a worse clinical profile, with higher comorbidity burden and frailty. Baseline variables according to eGFR group are depicted in Table 1. After a median follow up of 371 days, 58 patients (11.6%) died. One year mortality was higher in patients with worse renal function (8.8%, 11% and 21% according to normal, moderate and severe renal dysfunction respectively, p=0.036) and in frail patients (Figure 1). In multivariate analysis, frailty, but not severe renal dysfunction, was associated with one year mortality (frailty HR 2.05 95%CI 1.11-3.78 p 0.021, eGFR < 30 and 30-60 ml/min/1.72m2 HR 1.39 95%CI 0.62-3.09 p0.424 and 1.09 95%CI 0.58-2.09 p0.793 respectively). Conclusions Most HF patients ≥75 years have renal dysfunction. The association between renal function and clinical outcomes is different according to frailty status. CKD is related to worse prognosis only in non-frail patientsCumulative incidence of 1-year mortalityTable 1.Baseline characteristics

Clinical outcomes in >10,000 Asian vs >61,000 Non-Asian race patients with AF randomized to Warfarin vs DOACs: a patient-level meta-analyses from COMBINE AF

Abstract Background Randomized data comparing clinical outcomes of atrial fibrillation (AF) patients with Asian vs non-Asian races are limited. Methods Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48), we performed an individual patient-level meta-analysis to investigate and compare clinical outcomes of AF patients with self-defined Asian and non-Asian races adjusted for baseline characteristics. Standard-dose direct oral anticoagulants (SD DOAC) were defined as dabigatran 150mg bid; rivaroxaban 20mg (15mg) QD, apixaban 5 mg (2.5 mg) bid, or edoxaban 60 mg (30 mg) QD. Low-dose DOACs (DOACs [LD]) were defined as dabigatran 110 mg bid or edoxaban 30 mg (15mg) QD. Results There were 10,212 pts of Asian race and 61,471 non-Asian races in the COMBINE AF database. Compared with non-Asians, Asians were on average 3.2 yrs younger, 20 kg lighter, had worse renal function (mean CrCl 64.9 vs. 77.3 mL/min), and higher rates of prior stroke/transient ischemic attack (37.2% vs 26.6%), P<0.001 for each. The median value of time in therapeutic range of patients randomized to warfarin was lower in Asians than non-Asians (57.7% vs. 66.2%, P<0.001). In the warfarin arm, Asians had a higher adjusted risk of stroke/systemic embolic events (SEE), major bleeding (MB), ICH, GI bleeding (GIB), and net clinical outcome (NCO: stroke/SEE, MB, or death)(Figure; Upper panel). Compared to warfarin, SD DOACs significantly reduced the risks of stroke/SEE, MB, and NCO to a greater degree in Asians than non-Asians (HR stroke/SEE: Asians 0.65 vs Non-Asians 0.86; HR MB: Asians 0.62 vs Non-Asians 0.91; HR NCO: Asians 0.76 vs non-Asians 0.94; Pint <0.02 for each), while SD DOACs increased GIB only in non-Asians (Asian HR 0.92 [0.69-1.23] vs Non-Asians HR 1.41 [1.25-1.58], Pint 0.009; Figure Lower panel). Conclusions The adjusted risks of stroke/SEE and major bleeding with warfarin were higher in Asians compared to non-Asians. The benefits of DOACs over warfarin in preventing stroke/SEE, MB, and net clinical outcomes were significantly greater in Asians than non-Asians.

Venous Excess Ultrasound Score Is Associated with Worsening Renal Function and Reduced Natriuretic Response in Patients with Acute Heart Failure.

Background: The venous excess ultrasound score (VExUS) is used to objectify systemic venous congestion. The aim of the paper was to determine the association between VExUS grades and worsening renal function (WRF), reduced natriuretic response, diuretics resistance, and mortality in patients with acute heart failure (AHF). Methods: One hundred patients were included, and Doppler ultrasound of hepatic, portal, and renal veins was performed. Severity of congestion was graded using the VExUS score (grade 0, 1, 2, or 3). Sodium concentration in a spot urine sample was assessed in 2 h after the first loop diuretic administration and was adjusted for the prescribed dose of furosemide (31 mmol/40 mg). Diuretics resistance was defined as the need to double the starting dose of intravenous furosemide in 6 h. Results: Patients with VExUS grade 3 showed a higher incidence of WRF (OR: 11.17; 95% CI: 3.86-32.29; p < 0.001) and a decreased natriuretic response: a spot urine sodium content of <50 mmol/L (OR: 21.53; 95% CI: 5.32-87.06; p < 0.001) and an adjusted spot urine sodium content of <31 mmol/40 mg (OR: 9.05; 95% CI: 3.15-25.96; p < 0.001). The risk of diuretic resistance (OR: 15.31; 95% CI: 5.05-46.43; p < 0.001), as well as the need for inotropic and/or vasopressor support (OR: 11.82; 95% CI: 3.59-38.92; p < 0.001), was higher in patients with severe congestion. The hospital mortality rate increased in patients with VExUS grade 3 compared to in patients with other grades (OR: 26.4; 95% CI: 5.29-131.55; p < 0.001). Conclusions: Patients with AHF and VExUS grade 3 showed a higher risk of developing WRF, a decreased diuretic and natriuretic response, a need for inotropic and/or vasopressor support, and a poor prognosis during their hospital stay.

Absence of Kidney Tubular Injury in Patients With Acute Heart Failure With Acute Kidney Injury.

Worsening renal function (WRF) is common in hospitalized patients being treated for acute heart failure. However, discriminating clinically significant WRF remains challenging. In patients hospitalized with acute heart failure, we evaluated if blood and urine biomarkers of cardiac and kidney dysfunction were associated with adverse outcomes. We identified 175 of 927 participants in the AKINESIS study (Acute Kidney Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) who met criteria for stage 1 or 2 Kidney Disease: Improvement Global Outcomes acute kidney injury during the first 3 days of hospitalization. We measured 24 blood and urine biomarkers from specimens collected within 24 hours of meeting acute kidney injury criteria. The primary composite outcome consisted of worsening WRF (higher acute kidney injury stage), need for dialysis, or death at 30 days. Biomarkers' association with the composite outcome was assessed with logistic regression by tertiles and area under the curve (AUC). Of the 175 participants, 32 (18%) developed the primary composite outcome. Only history of chronic kidney disease was significantly different between those with and without the composite outcome. The highest tertile of plasma Gal-3 (galectin-3) and urine epidermal growth factor were associated with increased odds of the composite outcome compared with the lowest tertile in unadjusted analyses. After adjusting for serum creatinine, systolic blood pressure, and blood urea nitrogen, only the highest tertile of Gal-3 was associated with greater odds of the composite outcome (odds ratio, 4.6 [95% CI, 1.4-16.0). Gal-3 had the highest AUC (0.70 [95% CI, 0.58-0.82]), while epidermal growth factor had a lower AUC (0.63 [95% CI, 0.53-0.74]). Notably, urine biomarkers of kidney tubule injury were not associated with the composite outcome. Tubular injury does not occur in most patients with acute heart failure experiencing WRF, consistent with the functional mechanisms of WRF in this patient population. URL: https://www.clinicaltrials.gov/study/NCT01291836?term=NCT01291836&rank=1; Unique identifier: NCT01291836.

One-month DAPT after biodegradable-polymer everolimus-eluting stent implantation in women at high-bleeding risk: Insights from the POEM trial.

We conducted a prespecified subanalysis of the POEM trial to assess the association between sex and clinical outcomes following a short 1-month dual-antiplatelet-therapy (DAPT) period after percutaneous coronary intervention (PCI) with bioresorbable polymer everolimus-eluting stent (BP-EES) among patients at high bleeding risk (HBR). Shortening the DAPT period after PCI is an effective bleeding avoidance strategy with contemporary drug-eluting stents. Whether sex affects the risk of adverse events following PCI is still debated. Patients at HBR undergoing PCI with BP-EES were enrolled and treated with 1-month DAPT. If anticoagulation was needed, study participants received an oral anticoagulant (OAC) in addition to a P2Y12 inhibitor for 1 month, followed by OAC only thereafter. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. We report sex-based outcomes of patients included in the POEM study. We enrolled 129 (29.1%) women and 314 (70.9%) men. Women were older, with lower hemoglobin levels, and worse renal function. Accordingly, they had a trend for a greater number of HBR criteria fulfilled and a higher PARIS bleeding score. However, they were not at a significantly higher risk for the primary endpoint (men vs. women: 5.17% vs. 3.94%; HR 1.30; 95% CI: 0.48-3.54, p = 0.61), or any of the hemorrhagic and ischemic secondary endpoints. This prespecified subanalysis of the POEM trial suggests that 1-month DAPT following PCI with BP-EES may be a safe and effective therapeutic strategy for women at HBR.

Impacto de la natriuresis en el empeoramiento de la función renal durante un episodio de insuficiencia cardiaca aguda

Introduction and objectives: Worsening renal function (WRF) is a frequent complication in acute heart failure (AHF) with a controversial prognostic value. We aimed to study the usefulness of natriuresis to evaluate WRF.Methods: We conducted an observational, prospective, multicenter study of patients with AHF who underwent a furosemide stress test. The patients were classified according to whether WRF was present or absent and according to the median natriuretic response. The main endpoint was the combination of mortality, rehospitalization due to HF, and heart transplant at 6 months of follow-up.Results: One hundred and fifty-six patients were enrolled, and WRF occurred in 60 (38,5%). The patients were divided into 4 groups: a) 47 (30,1%) no WRF/low UNa (UNa ≤ 109 mEq/L); b) 49 (31,4%) no WRF/high UNa (UNa > 109 mEq/L); c) 31 (19,9%) WRF/low UNa and d) 29 (18,6%) WRF/high UNa. The parameters of the WRF/low UNa group showed higher clinical severity and worse diuretic and decongestive response. The development of WRF was associated with a higher risk of the combined event (HR, 1.88; 95%CI, 1.01-3.50; P = 0,046). When stratified by natriuretic response, WRF was associated with an increased risk of adverse events in patients with low natriuresis (HR, 2.28; 95%CI, 1.15-4.53; P = 0,019), but not in those with high natriuresis (HR, 1.18; 95%CI, 0.26-5.29; P = 0,826).Conclusions: Natriuresis could be a useful biomarker for interpreting and prognosticating WRF in AHF. WRF is associated with a higher risk of adverse events only in the context of low natriuresis.

P195 CARDIOVASCULAR OUTCOMES IN PATIENTS WITH AORTIC STENOSIS AND HYPERTENSION UNDERGOING AORTIC VALVE REPLACEMENT

Background and Objective: Aortic valve stenosis (AS) is most common valvular heart disease and in its severe form requires aortic valve replacement (AVR). The prevalence of both AS and arterial hypertension (HTN) increases with age and the conditions therefore often co-exist. Co-existence of AS and HTN is associated with higher global left ventricular (LV) pressure overload, more abnormal LV geometry and function, and more adverse cardiovascular outcome. Management of HTN in AS has historically been associated with prudence and concerns, mainly related to drug-induced potential adverse consequences. We evaluated the cardiovascular outcomes of patients with AS and HTN undergoing to AVR Methods: A retrospective cohort study where all the patients who underwent AVR between 2019- 2024, in a 4-level center in Bogotá, Colombia. A descriptive analysis was performed. Continuous variables were expressed as mean or median with their respective measure of dispersion, standard deviation or interquartile range (ICR), the categorical variables were expressed in proportions and absolute numbers. Results: We analyzed 1043 Patients with moderate/severe AS undergoing AVR, 64.3% (671 with HTN), median age for all of 69.8 years ICR (61.7-77.4) Hypertensive patient being older (72 years p&lt;0.0001). In the HTN group 57.8% were men, and more frequently they had diabetes and dyslipidemia comorbidities (p&lt;0.001) as well as greater baseline renal involvement (p&lt;0.001) comparatively with NO-HTN. In addition, hypertensive patient had better LVEF and were treated with ARA II/IECA (55,6% vs 19.4% p&lt;0.001), beta blockers (60.4% vs 47.3% p&lt; 0.001) and anti-calcium medication (13,1% vs 19,5% p&lt;0.001).Table 1. Cardiovascular outcomes showed greater tendency towards worsening of renal function. There were no statistically significant differences in mortality. Conclusions: AVR is presented as a safe procedure in patients with AS and HTN in developing countries. The institutional results show a safe technique, associated with low mortality rates. Hypertensive patients had more acute kidney injury in the post-surgical period, which leads us to propose kidney protection strategies in this group.

Diabetes mellitus in stable chronic heart failure and the combination with humoral activation, their association, and prediction of 2-year adverse outcomes. Data from the FAR NHL registry.

The study aims to describe the role of diabetes in patients with heart failure. In all, 1052 chronic heart failure patients were included in the FARmacology and NeuroHumoral Activation (FAR NHL) multicenter prospective registry. They had ejection fraction below 50% and were on stable medication for at least 1 month. More than one-third (38.9%) of the patients had diabetes mellitus (DM). Diabetic patients (N = 409) were older (median 67 vs. 64, p < 0.001), had higher body mass index (BMI) (30 vs. 28 kg/m2, p < 0.001), much more frequently had ischemic heart disease (71 vs. 47%, p < 0.001), hypertension (80 vs. 67%, p < 0.001), dyslipidemia (89 vs. 69%, p < 0.001), worse renal function (estimated glomerular filtration rate [eGFR] median 63 vs. 73 mL/min/1.73 m2, p < 0.001), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) (median 681 vs. 463 pg/mL, p = 0.003). All-cause death, left ventricle assist device implantation, and orthotopic heart transplantation were set as the combined primary end point, which was present in 15.5% (163 patients) within the 2-year follow-up. In the 2-year follow-up, 81.0% of patients with diabetes survived without a primary end point, while 85.4% of the patients without diabetes survived, the difference being on the verge of statistical significance (p = 0.089). DM is a statistically significant predictor of NT-proBNP value in univariate analysis, but it is not an independent predictor in a multivariate analysis. When the NT-proBNP level was high, the presence of DM did not influence the prognosis. The combination of diabetes and NT-proBNP levels may better stratify the prognosis of patients with chronic heart failure.

P098 CARDIAC REMODELING IN MICE TREATED WITH SODIUM OXALATE AND AORTIC STENOSIS

Background: Cardiovascular Diseases are one of the main global public health problems, with increasing mortality due to population aging and Hypertension (HTN). HTN is a risk factor for other diseases, such as aortic stenosis, renal dysfunction, and cardiac hypertrophy (CH). The hemodynamic overload caused by HTN affects the heart and kidneys, but the exact mechanisms of these alterations are not fully understood. Experimental models help study these mechanisms; however, a well-established model of CH with cardiorenal dysfunction does not yet exist. Objective: to evaluate whether the combination of cardiac hypertrophy, induced by transverse aortic constriction (TAC), and renal injury, induced by soluble sodium oxalate (OXA), can be a new model of CH with cardiorenal dysfunction. Methods: Male C57BL mice were randomized as follows: SHAM, receiving saline or OXA solution, and TAC, receiving saline or OXA solution. Echocardiography, direct blood pressure (BP) recording, metabolic cage, histology were performed to evaluate cardiac and renal function, hemodynamics, autonomic modulation, and baroreflex. Results: The TAC+OXA group showed the highest systolic BP(SBP) (SBP: SHAM: 122±5.24 vs. TAC+OXA: 160±5.24 mmHg, p&lt;0.01), increased double product (DP) (DP: SHAM: 64.65±4.76 mmHg/bpm vs. TAC: 89.53±5.85 mmHg/bpm, p=0.02), significant reduction in autonomic modulation (RMSSD: OXA: 12.5±1.8 vs. TAC+OXA: 2.8±0.2 ms, p&lt;0.01) and reflex tachycardia, eccentric hypertrophy, and worse renal function. The TAC group showed eccentric hypertrophy, increased BP variability (SD-SBP: SHAM: 2.97±0.07 mmHg vs. TAC: 5.63±0.57 mmHg, p≤0.01), diastolic dysfunction, and dilated left ventricle in diastole. The OXA group showed increased autonomic modulation and heart rate variability, renal damage characterized by inflammation, proximal tubule damage, and interstitial fibrosis when associated with TAC. All treated groups showed a significant reduction in reflex tachycardia. Conclusion: Transverse aortic constriction combined with OXA gavage is a model of CH with renal dysfunction, as the combination caused more significant renal damage, systemic hypertension, decreased autonomic modulation and baroreflex sensitivity, and eccentric hypertrophy with subsequent LV diastolic dysfunction.

SS-31 protects diabetic nephropathy progression: A systematic review of in vivo and in vitro studies

Context: Diabetic nephropathy is the leading cause of end-stage renal disease and also death in the world. Administration of Szeto-Schiller-31 (SS-31) as a potential therapeutic candidate that can decrease the renal function damage progressivity in diabetes needs to be comprehensively analyzed. Aims: To assess the protective effects of SS31 against the progressivity of diabetic nephropathy. Methods: This systematic review follows PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines 2020. Searches of databases (Pubmed, Science Direct, Scopus, ProQuest, and Springer) were done on 17 September 2023 in order to find articles related to the animal diabetic model and SS-31 treatment. Manual searches from medRxiv were also conducted to obtain additional evidence. Renal function, histopathology analysis, reactive oxygen species in vivo, and in vitro analysis were described. Results: There were six in vivo studies, each of which discussed the renal function, histopathology, and reactive oxygen species (ROS), and four in vitro studies that discussed ROS. The available data suggested that SS-31 improves kidney function by lowering urinary albumin excretion, proteinuria, serum creatinine, creatinine clearance, and BUN, supported by histopathological improvements. In addition, SS-31 also has the effect of lowering 8-hydroxy-2-deoxyguanosine (8-OHdG) level, malondialdehyde (MDA) level, and nicotinamide adenine dinucleotide phosphate (NADPH) expression. Conclusions: SS31 had a renoprotective effect that could prevent the worsening of renal function in diabetic mice. In addition, the results of histopathology and ROS analysis also support the positive results of SS-31 treatment. Further studies are required to confirm its findings.

Rationale and Design of PURE: A Randomized Controlled Trial to Evaluate Peritoneal Ultrafiltration with PolyCore™ in Refractory Congestive Heart Failure

Introduction: Peritoneal ultrafiltration (PUF) has been proposed as an additional therapeutic option for refractory congestive heart failure (RCHF) patients. Despite promising observational studies and/or case report results, limited clinical trial data exist, and so far, PUF solutions remain only indicated for chronic kidney diseases. In this article, we described a multicenter, randomized, controlled, unblinded, adaptive design clinical trial, about to start, investigating the effects of PolyCore™, an innovative PUF solution, in the treatment of RCHF patients. Methods: The Peritoneal Ultrafiltration in Cardiorenal Syndrome (PURE) study is a phase II, multicenter, randomized, controlled, unblinded, adaptive design clinical trial that aims to evaluate the safety and efficacy of PUF, using PolyCore™ as the investigational solution, in the treatment of RCHF patients who present with prominent right ventricular failure due to afterload mismatch, functional tricuspid regurgitation and enlarged cava vein consequent to intravascular fluid overload. Approximately 84 patients will be randomized 1:1 either to continue with their prescribed guideline-directed medical therapy or to add the PUF treatment on top of it. The primary objective is to evaluate if PUF treatment has an impact on the composite endpoint of the patient’s mortality or worsening of the patient’s condition such as hospitalization for cardiovascular causes, increasing the initial daily dose of loop diuretic or worsening of renal function. Statistical analysis for the primary endpoint will be standard survival analysis to estimate the failure rate at month 7 for each group via Kaplan-Meier curves. Sensitivity analysis and various secondary analyses, including a multiple events analysis, will be conducted to evaluate the robustness of the primary endpoint results. Safety will be evaluated for up to 12 months. Conclusion: The PURE study was designed to evaluate the safety and efficacy of peritoneal ultrafiltration with PolyCore™ on top of guideline-directed medical therapy in patients with RCHF, assuming a combined clinical endpoint of mortality or worsening patients’ condition. If successful, the treatment should allow for an improvement of the RCHF symptoms, decreasing hospitalization rate of patients.

Thiazide diuretics versus loop diuretics in stage 3-5 CKD: impact on cardiorenal outcomes

ABSTRACT Objectives The association between diuretic use and cardiorenal outcomes remains limited in patients with stage 3–5 chronic kidney disease (CKD) and hypertension. To address this gap, we aim to investigate the long-term clinical impact of diuretic use with its pharmacological classification in Taiwanese patients with stage 3–5 CKD and hypertension who were concurrently received angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). Methods Using data from the National Health Insurance Research Database (January 2008 to December 2019), we focused on individuals with stage 3–5 CKD receiving ACEIs/ARBs between 2010 and 2018. We categorized the cohort into non-diuretic, loop diuretic (furosemide), thiazide diuretic, and combination diuretic groups. We used a Cox proportional hazards regression model with propensity score matching to analyze the influence of diuretics on all-cause mortality, cardiovascular (CV) death, and cardiorenal adverse outcomes. Results The study included 59,719 patients, with 17,585 in the non-diuretic group and 42,134 in the diuretic group. Diuretics including furosemide use was significantly associated the risks of hospitalization for decompensated congestive heart failure (CHF), acute renal failure (ARF), end-stage renal disease (ESRD) requiring dialysis, CV mortality, and all-cause mortality (p-value <0.001). Thiazide diuretics showed no such adverse outcomes associations. The group receiving both thiazide and furosemide was more associated with all-cause mortality than the nondiuretic, thiazide, and furosemide monotherapy groups (all p-value <0.001). Conclusion Among stage 3–5 CKD patients on ACEIs/ARBs, loop diuretics exposure was associated with increased mortality and hospitalization for cardiorenal events, while thiazide diuretics exposure in isolation had no such associations. In the present data, we cannot evaluate the relationship between furosemide-associated adverse outcomes and worse renal function. These findings highlight the need for randomized controlled trials to assess the safety of loop diuretics in this population, urging caution in their prescription without a clear clinical indication.