Worse Renal Function Research Articles

#6682 RENAL ARTERY STENOSIS: A SINGLE CENTRE STUDY

Abstract Background and Aims Renal artery stenosis (RAS) is present from 1% to 5% in people affected by arterial hypertension and it is often associated with peripheral artery disease and coronary artery disease; as the matter of fact, it is commonly found in people undergoing cardiac catheterization (18-20%) or angiography for aorto-iliac and lower extremities diseases. The major cause of renal artery stenosis is an atherosclerotic lesion localized in the proximal segment or to the ostium. Clinical presentations are renovascular hypertension and ischemic nephropathy. The aim of the study is to define either endovascular treatment gives a significant benefit on renal function and blood pressure control, when associated to medical therapy. Method This is a retrospective study focused on patients who underwent renal artery angioplasty and stenting in the last ten years, from November 2011 to April 2021 in the Nephrology Department, at Sant'Andrea Hospital, La Spezia (Italy). The primary outcome was kidney function, while secondary outcomes were blood pressure and the number of antihypertensive drugs one year after the revascularization. Patients included in the study had uncontrolled and refractory arterial hypertension (PA ≥140/90 mmHg) and/or progressive worsening of renal function, secondary to bilateral or unilateral stenosis in one functional kidney, that was identified at the color-doppler ultrasound examination by a peak systolic velocity (PSV) >200 ml/min and an aortic-renal ratio >3,5. We found 36 patients who had these characteristics. They were all affected by chronic kidney disease (CKD) (mean±SD eGFR 25,3±15,3 ml/min/1,73 m2) equally divided into stage 3 (33%, eGFR 30-60 ml/min/1,73 m2), stage IV (31% eGFR 15-29 ml/min/1,73 m2) and stage V (36%, eGFR <15 ml/min/1,73 m2). Results Kidney function, measured as serum creatinine (SCr) (mg/dl), improved immediately after the revascularization (mean ± SD SCr after vs before 2,52 ± 1,61 vs 3,31 ± 2,47 mg/dl p<0.05), after 30 days (mean ± SD SCr after vs before creat. 2,36 ± 1,53 vs 3,19 ± 2,39 mg/dl p<0.05) and after one year (mean ± SD SCr after vs before creat. 2,04 ± 1,16 vs 2,99 ± 2,40 mg/dl p<0.05) (Fig. 1). Regarding arterial hypertension, a significant reduction of both systolic (SBP) and diastolic (DBP) blood pressure was detected in the subgroup of people under 75 years old (mean ± SD SBP after vs before, 144,62 ± 12,55 vs 168,18 ± 36,40 mmHg, p< 0,01; after one year vs before, 143,95 ± 21,10 vs 167,83 ± 38,16 mmHg, p<0.05) (mean ± SD DBP after vs before, 73,62 ± 9,62 vs 83,07 ± 21,75 mmHg, p< 0,05; after one year vs before 75,20 ± 9,02 vs 83,33 ± 23,10 mmHg, p = 0.07) (Fig. 2). The number of antihypertensive drugs dropped immediately after the angioplasty (mean ± SD tablets after vs before 2,28 ± 1,11 vs 3,21 ± 1,43, p<0.01), while after one year there was not a significant increase of therapy (mean ± SD tablets after one year vs before, 3,00 ± 1,41 vs 3,23 ± 1,42, p = 0,47), even if blood pressure was better controlled than before the procedure with the same amount of tablets (Fig. 3). Conclusion Although our population was quite small, we demonstrated the advantages of renal artery revascularization in atherosclerotic renovascular disease, as demonstrated by kidney function and blood pressure control. Our results contrast the larger studies considered, that found no relevant clinical benefit on renal function and incidence of major adverse cardiovascular and renal events by comparing patients treated with medical therapy alone or with medical therapy plus angioplasty. The different conclusions are probably due to our strict adhesion to the endovascular treatment indications, which consider the revascularization as the optimal strategy for a well-defined population.

Prevalence and Prognostic Implications of Worsening Renal Function After Acute Myocardial Infarction

We sought to investigate the relation between worsening renal function (WRF) at 1-year follow-up and clinical outcomes at 3 years after acute myocardial infarction (AMI). We analyzed data from 13,104 patients enrolled in the national AMI registry from November 2011 to December 2015. Patients with all-cause death, recurrent myocardial infarction (re-MI), and rehospitalization for heart failure at 1-year follow-up after AMI were excluded. A total of 6,235 patients were extracted and divided into WRF and non-WRF groups. WRF was defined as a ≥25% decrease in estimated glomerular filtration rate (eGFR) from baseline to 1-year follow-up. The primary outcome was 3-year major adverse cardiac events, a composite of all-cause death, re-MI, and rehospitalization for heart failure. On average, a -1.5 ml/min/1.73 m2/y rate of decrease in eGFR was exhibited, and 575 patients (9.2%) exhibited WRF at 1-year follow-up. After multiple adjustments, WRF at 1-year follow-up was independently associated with increased risks of major adverse cardiac events (adjusted hazard ratio 1.498, 95% confidence interval 1.113 to 2.016, p = 0.01), all-cause death, and re-MI at 3-year follow-up. Older age, female, diabetes mellitus, hypertension, non-ST-segment elevation AMI, anterior AMI, anemia, left ventricular ejection fraction <35%, and baseline eGFR <30 ml/min/1.73 m2 were identified as independent predictors of WRF after AMI. In conclusion, WRF at 1-year follow-up after AMI intuitively seems like a risk marker indicating multiple co-morbidities. Monitoring serum creatinine in patients at 1-year follow-up after AMI may help to identify those who are at the highest risk and guide effective long-term therapeutics.

Prediction of worsening postoperative renal function in older candidates to elective cardiac surgery: Choosing the best eGFR formula may not be enough

BackgroundThough renal impairment is highly prevalent in older patients and influence post-operative outcomes in cardiac surgery; its prognostic relevance is debated and not fully assessed by surgical risk scores. ObjectiveWe investigated the predictive role of estimated glomerular filtration rate formulas for in-hospital worsening renal function (WRF) after cardiac surgery. MethodsWe prospectively enrolled in single-center cohort study, patients aged ≥ 75 years candidate to elective cardiac surgery. Four creatinine-based equations were used to calculate estimated glomerular filtration rate (eGFR) formulas: Cockroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology, and Berlin Initiative Study 1 formulas. Each patient underwent geriatric and clinical evaluation before surgery with calculation of the Society of Thoracic Surgeons scores. In-hospital WRF was defined as a composite of an increase in SCr ≥0.5 mg/dl or the occurrence of grade III KDIGO acute kidney injury. The association between each eGFR equation, alone and in models including clinical variables, and WRF was analyzed using logistic regressions and ROC analysis. ResultsWRF occurred in 69 patients (19.8%), and the predictors of WRF were previous acute myocardial infarction, hypertension, 4-mt gait speed performance, and preoperative eGFR, irrespective of the equation used. With all equations, inclusion of these additional variables in the logistic regression models improved the prediction of WRF (AUCs 0.798–0.810). ConclusionsAn accurate assessment of renal function and of physical performance should be incorporated into cardiac surgery risk scores to improve prediction of in-hospital WRF and, hence, risk stratification in older adults undergoing elective cardiac surgery.

Risk stratification for worsening renal function and renal decline in heart failure patients with reduced ejection fraction after sacubitril/valsartan treatment

BackgroundIn the real-world setting, data regarding renal decline following sacubitril/valsartan treatment are lacking. This study aimed to develop a scoring system to predict renal outcome in sacubitril/valsartan-treated patients. MethodsBetween 2017 and 2018, a total of 1505 heart failure patients with reduced ejection fraction (HFrEF) undergoing sacubitril/valsartan treatment were consecutively enrolled from 10 hospitals to serve as the derivation cohort. Another 1620 HFrEF patients receiving sacubitril/valsartan were included as the validation cohort. Worsening renal function (WRF) was defined as a serum creatinine increase of >0.3 mg/dL and/or >25 % at 8 months of sacubitril/valsartan treatment. The derivation cohort was used to identify independent predictive factors for WRF through multivariate analysis, which were then used to develop the risk score system. ResultsAmong the 3125 HFrEF patients, 689 (22.0 %) patients had WRF at 8 months following sacubitril/valsartan treatment. In the derivation cohort, six prognostic factors (age, functional class, history of peripheral arterial disease, diabetes mellitus, gout or hyperuricemia, and serum albumin level) were independently associated with WRF, and were combined into a risk predicting score. This score showed accurate discrimination in the derivation and validation cohorts (Harrell's concordance indexes 0.74 and 0.71, 95 % confidence intervals 0.71–0.78 and 0.69–0.74, respectively). Patients with a higher risk score experienced a more rapid decline in renal function, poorer clinical outcomes, and a higher rate of discontinuation of sacubitril/valsartan treatment. ConclusionsThis study developed a score for WRF after sacubitril/valsartan treatment, which may assist clinicians with risk stratification and therapeutic decision-making.

Analysis of Oral Anticoagulant Dosing and Adherence to Therapy Among Patients With Nonvalvular Atrial Fibrillation

Although reduced doses of direct oral anticoagulants (DOACs) are approved for patients with nonvalvular atrial fibrillation (NVAF) at high risk of bleeding, little is known about dosing accuracy, particularly in patients with renal dysfunction. To determine whether underdosing of DOACs is associated with longitudinal adherence to anticoagulation. This retrospective cohort analysis used data from the Symphony Health claims data set. This national medical and prescription data set comprises 280 million patients and 1.8 million prescribers in the US. Patients included had at least 2 claims for NVAF between January 2015 and December 2017. The dates of analysis for this article were from February 2021 to July 2022. This study included patients with CHA2DS2-VASc scores of 2 or higher who were treated with a dose of DOACs who did and did not meet label-specified criteria for dose reduction. Logistic regression models examined factors associated with off-label dosing (ie, dosing not recommended by US Food and Drug Administration [FDA] labeling), the association of creatinine clearance with recommended DOAC dosing, and the association of DOAC underdosing and excess dosing with 1-year adherence. Among the 86 919 patients included (median [IQR] age, 74 [67-80] years; 43 724 men [50.3%]; 82 389 White patients [94.8%]), 7335 (8.4%) received an appropriately reduced dose, and 10 964 (12.6%) received an underdose not consistent with FDA recommendations, meaning that 59.9% (10 964 of 18 299) of those who received a reduced dose received an inappropriate dose. Patients who received off-label doses of DOACs were older (median [IQR] age, 79 [73-85] vs 73 [66-79] years) and had higher CHA2DS2-VASc scores (median [IQR], 5 [4-6] vs 4 [3-6]) compared with patients who received appropriate doses (as recommended by FDA labeling). Renal dysfunction, age, heart failure, and the prescribing clinician being in a surgical specialty were associated with dosing not recommended by FDA labeling. Almost one-third of patients (9792 patients [31.9%]) with creatinine clearance less than 60 mL per minute taking DOACs were either underdosed or excess-dosed not consistent with FDA recommendations. For every 10-unit decrease in creatinine clearance, the odds of the patient receiving an appropriately dosed DOAC was lower by 21%. Treatment with underdosed DOACs was associated with a lower likelihood of adherence (adjusted odds ratio, 0.88; 95% CI, 0.83-0.94) and higher risk of anticoagulation discontinuation (adjusted odds ratio, 1.20; 95% CI, 1.13-1.28) by 1 year. In this study of oral anticoagulant dosing, DOAC dosing that did not follow FDA label recommendations was observed in a substantial number of patients with NVAF, occurred more frequently in patients with worse renal function, and was associated with less-consistent long-term anticoagulation. These results suggest a need for efforts to improve the quality of DOAC use and dosing.

HYPERTENSION AND HYPERALDOSTERONISM

Objective: describe the importance of investigating secondary hypertension in cases of hypertension that is difficult to control through clinical signs Design and method: Case Report: Patient R.A., female, 47 years old, hypertensive for seventeen years appears in the emergency department with a report of a hypertensive peak in a periodic consultation. At the time she was asymptomatic with a blood pressure of 260 x 120 mmHg. The electrocardiogram showed sinus rhythm with reduced T wave amplitude, increased U wave amplitude, and increased QT interval. The laboratory test showed hypokalemia associated with metabolic alkalosis, and slight elevation of renal slag. Results: The investigation of arterial hypertension secondary to primary hyperaldosteronism was initiated with plasma aldosterone dosage and plasma renin activity, showing an AP/ARP ratio &gt; 100 ng/mL/h. Computed tomography of the abdomen and pelvis showed adenoma in the right adrenal, which was resected laparoscopically. One month after hospital discharge, the patient returns to the emergency room with nausea, vomiting and general malaise. Laboratory with hyperkalemia and worsening of renal function. At this moment, the patient was using a potassium-sparing diuretic, considered as a possible cause of the disorder, since other tests performed did not show any alteration. The diuretic was discontinued, with clinical and laboratory evolutionary improvement. The patient is discharged from hospital, with adequate blood pressure control and stable renal function. Conclusions: Primary hyperaldosteronism is a clinical condition determined by excessive production of aldosterone, caused by bilateral adrenal hyperplasia or unilateral adenoma. Hyperaldosteronism is suspected when we observe hypertension associated with difficult control, hypokalemia, adrenal incidentaloma. The investigation continues through serum levels of aldosterone and renin activity, as well as imaging tests, such as computed tomography. Laparoscopic surgery is indicated, with a success rate between 30-60%. It is important to emphasize that regular follow-up after the surgical procedure is essential to control blood pressure, with the aim of preventing the progression of renal hypertensive disease.

INTRARENAL RESISTANCE INDEXES AND NONALCOHOLIC FATTY LIVER DISEASE IN UNTREATED HYPERTENSIVE PATIENTS

Objective: Nonalcoholic Fatty Liver Disease (NAFLD) is reaching epidemic proportions with a prevalence in the adult population of approximately 25%. A continuum of hepatic conditions is embraced by NAFLD, from plain steatosis to liver fibrosis that can be assessed by use of surrogate clinical/biochemical scores. Recent studies have reported an association of NAFLD with chronic renal failure and its progression in the general population. Because increasing of intrarenal resistance indexes (IRI) anticipate worsening of renal function in hypertension we investigated their relationships with liver steatosis and fibrosis scores in never treated hypertensive patients. Design and method: In a cross-sectional study of 111 treatment-naïve, essential hypertensive patients we measured IRI and calculated scores of liver steatosis (LFS: liver fatty score; FLI: fatty liver index; HIS: hepatic steatosis index) and liver fibrosis (NFS: NAFLD fibrosis score; APRI: aminotransferase to platelet ratio index; FIB-4: fibrosis 4). Results: IRI were significantly and directly correlated with the LFS (r = 0.240, P = 0.025) while a borderline correlation was observed with NFS (r = 0.206, P = 0.052). No significant relationships were observed with the remaining liver steatosis and fibrosis scores. Multivariate analysis indicated an independent association of IRI and LFS (B = 0.309, P = 0.030). Conclusions: In treatment-naïve hypertensive patients IRI are independently associated with a score of liver steatosis suggesting that NAFLD might contribute to worsening of renal function in these patients.

P66: Incidence of DVT formation in patients requiring temporary mechanical circulatory support for cardiogenic shock

Background: After the 2018 UNOS organ allocation change, temporary mechanical circulatory support (tMCS) has increased in managing acute decompensated heart failure (ADHF) as a bridge to transplant, recovery, or durable VAD. However, patients supported with tMCS are more prone to complications. Deep venous thrombosis (DVT) is one of the most common complications in this patient population. DVT is associated with an increased risk of pulmonary embolism, stroke, chronic venous insufficiency, and increased length of hospital stays. We aimed to identify the incidence of DVT in ADHF patients supported with tMCS. Method: We performed a retrospective review of patients with ADHF who had undergone heart or heart/kidney transplantation between January 2021 and November 2022 at Mayo Clinic in Florida. Patient data were extracted from the electronic health record after IRB approval as exempt for retrospective chart review was obtained. Our primary outcome was DVT during the transplant, diagnosed by venous duplex ultrasonography. Results: 93 patients with ADHF were found during our review period, of which 46 (49%) developed a DVT. The median age was 60 years (53 – 67), with 65% male. All but one DVT was in the upper extremity. Within the DVT population, 75% were hypertensive (p <.001), 64% were diabetic (p =.003), 78% had hyperlipidemia (p<.001), and had elevated mean creatinine of 2.16 vs. 1.55 (p =.04). A total of 44 patients required tMCS, of these, 26 patients developed DVT (59%) which was statistically significant compared to 18 that did not develop DVT while on tMCS, p =.04. The combination of support was as follows: 27 axillary Impella 5.5 alone, 5 VA ECMO without LV vent, 1 VA ECMO with IABP vent, 4 VA ECMO with Impella 5.5 vent, and 7 intra-aortic balloon pumps only. Ischemic cardiomyopathy was not a significant risk for DVT, p =.372. The median ejection fraction was 25% (15 -55). The median LOS was 48 days (31 – 74). Patients with DVT were found to have a significantly lower BMI, 26.4 vs 29.3 (p =.002), as well as a significantly shorter cardiopulmonary bypass time of 187min vs. 296 min (p <.001). Conclusions: We found increased rates of DVT in patients utilizing all forms of tMCS with ADHF. Factors influencing the development of DVT may relate to an overall increased inflammatory state, evidenced by our data showing significant differences in rates of hypertension, diabetes, hyperlipidemia, worse renal function, and sarcopenia. Chronicity of disease, time in the hospital, and the need for more procedures may also influence DVT risk in patients awaiting transplantation or LVAD.

Outcomes of renal function and efficacy in patients with muscle invasive bladder cancer treated by tislelizumab-based immunochemotherapy.

e16608 Background: The occurrence PD-1 ICIs brings a new era of treatment for bladder cancer (BC). Although the safety and efficacy of most PD-1 ICIs have been certified progressively, whether they can be used in patients (pts) with renal impairment is always a concern for clinicians. Consequently, we intend to investigate the variation of renal function and efficacy of PD-1 ICIs based immunochemotherapy for pts with muscle invasive bladder cancer (MIBC) and renal insufficiency in short term. Methods: Our study relied on population of the TRUCE-01 trial (NCT04730219), an open-label, single-arm phase II study of tislelizumab based immunochemotherapy in pts with MIBC. Data of pts, including demographic information, imaging and pathological assessment of efficacy, and serum creatinine (SCr) level in baseline, after the first, second and third cycle (C1, C2 and C3) of treatment was collected and analyzed retrospectively. We calculated at estimated glomerular filtration rate (eGFR) according to CKD-EPI formula 2009, and divided pts into different groups according to baseline eGFR, in reference to CKD categories in the K-DIGO 2012 guidelines. Results: 74 pts have been included in our research in total. The median age was 69.5 years (IQR 61.7-75.0) and 56 (75.7%) were male. Median SCr in baseline was 77.4umol/L (IQR 67.8-96.6), while median eGFR was 84.6 (IQR 63.6-94.0) (the unit of eGFR is mL/min/1.73 m2). At baseline, 25 pts were classified as G1 (eGFR≥90), 36 as G2(eGFR &lt;90 and≥60), 12 as G3 (eGFR &lt;60 and ≥30), and 1 as G4 (eGFR &lt;30 and≥15). No significant difference was found in eGFR between pts with CKD G1-2 in comparison to baseline and after C1, C2, C3 of treatment (All p&gt;0.05). In pts with CKD G3-4, it is notable that eGFR may improve when the C1, C2 and C3 completed, in comparison to the baseline (p=0.087, p=0.046, p=0.114 in Wilcoxson test, p=0.082 in Repeated Measures ANOVA). 48 (64.9%) pts received 3 cycles of ICIs and underwent an operation. 24 of 48 (50%) pts received radical cystectomy (RC) and others were treated by maximal TURBT. All of them have conducted efficacy evaluation by both radiographic test and pathology. It is noted that no statistical difference in outcomes between Group G1-2 and G3-4 (p=0.772). Conclusions: Despite renal impairment is common in pts with MIBC, PD-1 immunotherapy is generally safe for kidney of MIBC patients with renal insufficiency and have no influence on efficacy in the short term. The potential improvement in eGFR of patients with worse renal function and its mechanism is essential to be revealed and verified. [Table: see text]

Phase Ib neoadjuvant CG0070 and nivolumab (N) for cisplatin (C)-ineligible muscle invasive bladder cancer (MIBC).

e16613 Background: CG0070 is a replication-competent oncolytic adenovirus engineered to target RB deficient tumor cells and to express GM-CSF. CG0070 has previously demonstrated safety and efficacy against BCG-exposed high risk non-muscle invasive bladder cancer through tumor lysis and anti-tumor immune activation. We tested the safety and efficacy of CG0070 in combination with N as neoadjuvant therapy for MIBC in C-ineligible patients in this study (NCT04610671). Methods: C-ineligible pts with MIBC (cT2-4a, N≤1) were enrolled. Pts received 6 weekly intravesical CG0070 (1x1012vp) and 2 doses of N at wks 2 and 6, followed by radical cystectomy (RC). The primary objective is safety of CG0070+N as measured by CTCAEv5.0. Secondary objective is to assess pathologic response (PaR) (pT0N0) and 1yr event free survival (EFS). Exploratory objectives include the assessment of correlation between PaR with baseline 1) E2F expression; 2) immune infiltration; 3) PD-L1 expression; and 4) TLS expression. Results: Between Nov 2020 and Feb 2023, 21 pts were enrolled with median age 75yrs, 81% male, 33% &gt; cT2; 1 pt refused RC but was included in the ITT population. Treatment was stopped after 1 infusion of CG0070 in 1 pt due to treatment unrelated worsening of renal function. The overall rate of &gt;grade 3 AEs was 12/20 (60%), and the vast majority were related to RC (83%). Immune related AEs were seen in 1 pt, who had grade 2 autoimmune thyroiditis. There was no delay in time to RC and no unexpected surgical complications from treatment. Overall, 1 pt was unevaluable for efficacy, 2 pts progressed prior to RC, PaR was observed in 8/15 (53%) evaluable pts, and an additional pt had negative post-treatment biopsy but refused RC. On exploratory analysis, treatment response correlated with increased maturation of tertiary lymphoid structures and immunogenicity to bespoke tumor neoantigens. Conclusions: Neoadjuvant CG0070+N is safe and effective in C-ineligible pts with MIBC. This combination was well tolerated without any delays in RC and induced an overall response rate of 50%. Clinical trial information: NCT04610671 .

Relationship between positive end-expiratory pressure levels, central venous pressure, systemic inflammation and acute renal failure in critically ill ventilated COVID-19 patients: a monocenter retrospective study in France.

The role of positive pressure ventilation, central venous pressure (CVP) and inflammation on the occurrence of acute kidney injury (AKI) have been poorly described in mechanically ventilated patient secondary to coronavirus disease 2019 (COVID-19). This was a monocenter retrospective cohort study of consecutive ventilated COVID-19 patients admitted in a French surgical intensive care unit between March 2020 and July 2020. Worsening renal function (WRF) was defined as development of a new AKI or a persistent AKI during the 5 days after mechanical ventilation initiation. We studied the association between WRF and ventilatory parameters including positive end-expiratory pressure (PEEP), CVP, and leukocytes count. Fifty-seven patients were included, 12 (21%) presented WRF. Daily PEEP, 5 days mean PEEP and daily CVP values were not associated with occurrence of WRF. 5 days mean CVP was higher in the WRF group compared to patients without WRF (median [IQR], 12 mm Hg [11-13] vs. 10 mm Hg [9-12]; P=0.03). Multivariate models with adjustment on leukocytes and Simplified Acute Physiology Score (SAPS) II confirmed the association between CVP value and risk of WRF (odd ratio, 1.97; 95% confidence interval, 1.12-4.33). Leukocytes count was also associated with occurrence of WRF in the WRF group (14 G/L [11-18]) and the no-WRF group (9 G/L [8-11]) (P=0.002). In mechanically ventilated COVID-19 patients, PEEP levels did not appear to influence occurrence of WRF. High CVP levels and leukocytes count are associated with risk of WRF.

Outpatient intravenous diuresis in a rural setting: safety, efficacy, and outcomes.

To evaluate the safety, efficacy, and outcomes of outpatient intravenous diuresis in a rural setting and compare it to urban outcomes. A single-center study was conducted on 60 patients (131 visits) at the Dartmouth-Hitchcock Medical Center (DHMC) from 1/2021-12/2022. Demographics, visit data, and outcomes were collected and compared to urban outpatient IV centers, and inpatient HF hospitalizations from DHMC FY21 and national means. Descriptive statistics, T-tests and chi-squares were used. The mean age was 70 ± 13 years, 58% were male, and 83% were NYHA III-IV. Post-diuresis, 5% had mild-moderate hypokalemia, 16% had mild worsening of renal function, and 3% had severe worsening of renal function. No hospitalizations occurred due to adverse events. The mean infusion-visit urine output was 761 ± 521 ml, and post-visit weight loss was -3.9 ± 5.0 kg. No significant differences were observed between HFpEF and HFrEF groups. 30-day readmissions were similar to urban outpatient IV centers, DHMC FY21, and the national mean (23.3% vs. 23.5% vs. 22.2% vs. 22.6%, respectively; p = 0.949). 30-day mortality was similar to urban outpatient IV centers but lower than DHMC FY21 and the national means (1.7% vs. 2.5% vs. 12.3% vs. 10.7%, respectively; p < 0.001). At 60 days, 42% of patients had ≥1 clinic revisit, 41% had ≥1 infusion revisit, 33% were readmitted to the hospital, and two deaths occurred. The clinic avoided 21 hospitalizations, resulting in estimated cost savings of $426,111. OP IV diuresis appears safe and effective for rural HF patients, potentially decreasing mortality rates and healthcare expenses while mitigating rural-urban disparities.

P239 BASELINE HIGH RENAL RESISTANCE INDEX IS ASSOCIATED WITH WORSENING OF RENAL FUNCTION IN PATIENTS UNDERGOING CARDIAC SURGERY

Abstract Renal resistance index (RRI) is a parameter which is easily evaluable by the echo Doppler technique and which has been demonstrated to predict worsening of renal function (WRF) in patients affected by chronic heart failure as well as among those undergoing coronary angiography. The aim of this study was designed to evaluate the role of the RRI in predicting WRF after cardiac surgery. Methods Thirty–one patients were enrolled. Their clinical characteristics are shown in Table 1. All patients underwent cardiac surgery. Before surgery, RRI was evaluated according to Peurcelot’s formula by renal interlobular arteries pulsed Doppler. WRF was defined as an increase in serum creatinine of &amp;gt; 0.3 mg/dl associated with a change &amp;gt; 25% or the need of renal replacement therapy due to severe acute kidney injury. Results Among the patients in 12 WRF occurred, in 10 a worsening of creatinine serum levels and in 2 a severe AKI requiring RRT were observed. As shown in Table 1, RRI and the presence of peripheral artery disease were the only parameters which were significantly different among patients with and without WRF, whereas no difference in GFR values was observed. Baseline RRI showed a significant AUC of 0.74 (95% CI, 0.55–0.93) whereas baseline GFR of 0.52 (95% CI, 0.28–0.75) was not significant. Conclusions Among patients with WRF after cardiac surgery an increased RRI but not a different baseline GFR is observed. This parameter could allow a more accurate stratification of the risk of cardiorenal syndrome worsening among patients candidated to cardiac surgery.

P481 PREDICTIVE FACTORS OF CLINICAL OUTCOME IN PATIENTS WITH AORTIC STENOSIS: DATA FROM THE VENETO REGISTER

Abstract Background Aortic valve stenosis represents the most relevant valve disease in the Western world, with a mortality rate exceeding 50%. Calcific aortic valve stenosis was once considered a passive process of the valve deposition of calcium salts, but is now considered a cell–mediated disease. The aim of the present study is to search for predictors of mortality, cardiovascular events and valve replacement in patients with aortic stenosis. Materials and Methods A subgroup of 140 patients affected by moderate–severe aortic valve stenosis from the Cardiology departments of the Treviso Hospital and the High Specialization Hospital of Motta di Livenza included in the Veneto Register. For each patient, information relating to deaths, cardiovascular events and valve staging was therefore collected over time. Results The deceased were 36% of which 22.9% without having replaced the valve. The mean follow–up was 24.99±21.72 months. In the follow–up, the deceased were characterized by an older age, a greater frequency of ischemic heart disease, atrial fibrillation and chronic kidney disease (CKD), a worse eGFR, a higher phosphate level. Among the Cox regression biohumoral data, serum phosphate was significantly associated with mortality in the univariate survey, and eGFR values were also always independently significantly associated with mortality. Kaplan Meyer curves also showed significant differences in the risk of CV events over time between groups with eGFR values greater than equal and less than 60 mL/min. Conclusions The results of the study suggest that the pathology appears to be linked to senescence processes and shares a common basis with atherosclerotic pathology, but also appears to be influenced in its evolution by further determinants such as CKD and blood phosphorus values. These considerations prompt us to reflect on the need for studies aimed at understanding the pathogenetic mechanisms of the proven relationship between cardiovascular MACE and phosphorus values, and that between worse renal function and cardiovascular mortality/morbidity. On the other hand, it seems urgent to be able to propose in the near future an internationally shared prognostic score that considers these predictive variables and can help us to better stratify the clinical evolution of aortic stenosis and influencing the surgical timing.

P332 A CASE OF METABOLIC ACIDOSIS AFTER INITIATION OF SGLT2–I THERAPY IN HEART FAILURE WITH REDUCED EJECTION FRACTION

Abstract In July 2022 C.M., a 58–year–old woman, was admitted to our Heart Failure Outpatient Clinic. Patient with permanent AF undergoing DOAC therapy, previous double mitral and tricuspid valve replacement with bioprosthesis. As comorbidities she had stage IIIb CKD, previous ischemic stroke without outcome, multifactorial anaemia, asthma, ulcerative rectocolitis non–responsive to biological therapy. Since April 2022 progressive reduction in exercise tolerance with dyspnoea for previously well–tolerated exertion, with finding of severe left ventricular systolic dysfunction (FE 25%) due to widespread hypokinesia previously unknown. In September angiographic control confirmed the absence of coronary artery disease. Amiodarone therapy was started for frequent runs of VT. Cardiac MRI confirmed FE 27% with fibrosis of the interventricular septum and lower basal wall of non–ischemic appearance. In view of the clinical–instrumental findings, a single–chamber ICD pacemaker was implanted and the therapy for heart failure with reduced FE was optimised with the introduction of Sacubitril/Valsartan (later discontinued due to hypotension), MRA and SGLT2–I (Empagliflozin). Due to the persistence of labile haemodynamic compensation, an indication was given to perform three cycles of Levosimendan infusion at our Day Hospital. The routine EGA taken during the first infusion cycle showed metabolic acidosis in the absence of significant worsening of renal function (Fig. 1) with mild hypobicarbonatemia and electrolytes in the normal range. On the assumption that the acidosis was secondary to the introduction of SGLT2–I (about two months earlier), Empagliflozin was discontinued. One week after discontinuation, the control EGA (Fig. 1) showed resolution of the acidosis, with a substantially stable glomerular filtrate, so that discontinuation of the drug was confirmed. Conclusions In the literature there are reviews and case reports of euglycaemic diabetic ketoacidosis (euDKA) in DM2 patients on SGLT2–I therapy although there are currently only hypotheses regarding the pathophysiological mechanism. The possibility of inducing acidosis with hypobicarbonatemia in the absence of worsening renal function is unclear. A ‘Fanconi–like‘ mechanism could be hypothesised with induction of type 2 tubular acidosis with bicarbonate loss due to glycosuria.

P218 WILD TYPE TRANSTHYRETIN CARDIAC AMYLOIDOSIS (WTATTR) AND HEART FAILURE WITH REDUCED EJECTION FRACTION (HFREF): CAN ANGIOTENSIN RECEPTOR/NEPRILYSIN INHIBITORS (ARNI) BE A THERAPEUTIC OPTION?

Abstract Background wtATTR is associated with high mortality rate, median survival from diagnosis is 43 months and mortality reaches 50% at 4 years. Most patients (pts) present with heart failure and preserved ejection fraction (HFpEF), fewer with HFrEF. Tafamidis is the only modifying–disease agent available in Italy and therapeutic strategy is based on diuretic titration. Beta blockers and therapies for neurohormonal antagonism have raised concerns about their efficacy and safety. The role of ARNI has not been explored. We report our experience of the use of ARNI in pts with wtATTR not eligible to Tafamidis due to advanced NYHA classes. Cases 4 male pts (median age 81 y.o.) received diagnosis of wtATTR between 2018 and 2019 when Tafamidis was not available. Median left ventricular ejection fraction (mLVEF) at the time was 51%. 2 years later they presented with acute HFrEF (Tab1–T0), NYHA classes III–IV with median systolic blood pressure 105 mmHg. Average N–terminal pro natriuretic peptide (NTproBNP) levels were 13888pg/ml and median estimated glomerular filtration rate (eGFR) was 36 mil/min/1,72m2. mLVEF was 23%. Once congestion was relieved pts started Sacubitril/Valsartan (S/V) with titration of dose. At 6 months follow–up (FU) (Tab1–T1) pts were downgraded to NYHA class II and no symptomatic hypotension was reported. Average NTproBNP levels were reduced to 7.800pg/l, only mild worsening of renal function was reported (median eGFR 31mil/minx1.73m2). Absolute increase of mLVEF (46%) was shown on echocardiography. At 12 months FU (Tab 1–T2) pts were clinically stable in NYHA class II, NTproBNP median values had mildly increased to 9700pg/ml and average eGRF was stable (30mil/minx1.73m2). Echocardiogram highlighted minimal reduction of mLVEF compared to previous result (41%). During FU only 1 of the pts required hospitalization for intravenous diuretic therapy and S/V was temporarily suspended. Conclusion The efficacy of S/V in HFrEF is well known. Our brief study proves that ARNI can be tolerated in frail pts affected by wtATTR with no other therapeutic options, guaranteeing a long hospitalization–free period with improvement in quality of life. The result may be purely due to the natriuretic effect of ARNI in patients so strictly reliant on volemic state. More complicated effects may be mediated by neprilisin on amyloid protein; further studies are warranted to establish the role of ARNI in wtATTR.

P85 REAL WORLD EXPERIENCE ON THE USE OF SGLT2–I IN ELDERLY PATIENTS WITH HFREF

Abstract SGLT2–i have been shown to improve prognosis in patients with heart failure with reduced ejection fraction (HFrEF) in randomized clinical trials (RCTs). However, at the moment, we have little data on the use of these drugs in clinical practice, both in terms of safety and efficacy profile. Objectives To describe the characteristics of HFrEF outpatients who started SGLT2–i in clinical practice; evaluate tolerability and the effect on clinical and biohumoral parameters. Methods We prospectively analyzed patients who started SGLT2–i in our Heart Failure clinic. The baseline characteristics, the variations of bio–humoral and clinical parameters were recorded, as well as the onset of adverse effects leading to drug suspension after one month. Results We evaluated 37 patients, with a mean age of 77.7± 8.5 years (65% over 75). The baseline characteristics of the population compared to that of the treatment arms of the RCTs are shown in Fig.1. Most patients were in NYHA II (62%), with ischemic etiology (65%), with reduced EF (mean 34.7± 5.1%) and nearly half of the patients received ICD or CRT–D (43.2%). At the one month follow–up, there was a significant reduction in NYHA class (Fig. 2)and furosemide dose (36.3 vs 53.2 mg, p&amp;lt;0.001), without a significant change in NTproBNP values ​​(2499 vs 2431 pg /mL, p=0.804). Furthermore, there was a reduction in systolic blood pressure (115 vs 120 mmHg, p=0.029) with no significant increase in the incidence of orthostatic hypotension (27% vs 21%, p=0.48). In line with the trials, there was a slight, non–significant worsening of renal function (CKD–EPI 52.9 vs 55.9 mL/min, p=0.10). At one month, no patients experienced any adverse effects leading to SGLT2–i discontinuation. Conclusions In this preliminary analysis, after one month of SGLT2–i therapy in elderly patients, there was a clinical and hemodynamic improvement as demonstrated by the improvement of the NYHA class and the reduction of the diuretic therapy. SGLT2–i have been shown to be relatively safe, with no adverse effects and no increased risk of orthostatic hypotension or significant worsening of renal function.

P217 SHORT–TERM EFFECTS OF DAPAGLIFLOZIN ON CARDIAC BIOMARKERS, FLUID RETENTION, RENAL AND PULMONARY FUNCTION IN HFREF PATIENTS: NOT AS GOOD AS EXPECTED

Abstract Background Sodium–glucose co–transporter–2 inhibitors (SGLT2–i) are currently a standard therapy for patients with heart failure with reduced ejection fraction (HFrEF). Still, their potential benefits on biomarkers, respiratory function parameters and fluid retention have not been extensively studied. Bioimpedance vector analysis (BIVA) has emerged as a new tool capable of assessing congestion, providing an estimate of the total body water and hydration index (HI). BIVA is more accurate than NT–proBNP in detecting peripheral congestion in chronic heart failure and can be used to evaluate the effects of the treatment. This study aims to assess the short–term effects of Dapagliflozin on spirometry, diffusing capacity of the lungs for carbon monoxide (DLCO), cardiac biomarkers, and BIVA. Methods Stable HF patients (EF &amp;lt;40%, NYHA class II or III) eligible for SGLT2–I therapy according to guidelines underwent standard spirometry, DLCO, BIVA and venous blood sampling at baseline (V0) and after 2–4 weeks of therapy (V1). Results Patients characteristics (N=32) at baseline are shown in Table 1. None of the patients interrupted the treatment and/or experienced adverse events. After 26±6 days, we observed worsening of renal function (eGFR from 73.1±28.5 mL/min/1.73m2 to 67.4±27.0 mL/min/1.73m2, p&amp;lt;0.001) and potassium levels (4.36±0.36 mEq/l vs 4.58±0.57 mEq/l, p= 0.017). There were no significant changes in NT–proBNP levels (1378 [615–2542] ng/l vs 1034 [554–2552] ng/l, p= 0.538). HI, total body water, DLCO and spirometry values did not change. On the contrary, a mild reduction in hsTnI was observed (13.88 [9.24–26.8] ng/l vs 11.58 [7.7–24.2] ng/l). Conclusions Our study did not detect short–term effects of Dapagliflozin on spirometry values, DLCO, fluid retention and NT–proBNP. As revealed in DAPA–HF trial, a mild worsening of potassium and serum creatinine levels was observed. Taken together, these results suggest that the favourable effects of Dapagliflozin could unfold over a longer period of time. A more extended follow–up and a larger population are needed to confirm these preliminary data.

Corazón univentricular sin cirugía de Fontan: el tipo de paliación importa

Introduction and objectivesThere is scarce information on patients with single ventricle physiology (SVP) and restricted pulmonary flow not undergoing Fontan circulation. This study aimed to compare survival and cardiovascular events in these patients according to the type of palliation. MethodsSVP patient data were obtained from the databases of the adult congenital heart disease units of 7 centers. Patients completing Fontan circulation or developing Eisenmenger syndrome were excluded. Three groups were created according to the source of pulmonary flow: G1 (restrictive pulmonary forward flow), G2 (cavopulmonary shunt), and G3 (aortopulmonary shunts±cavopulmonary shunt). The primary endpoint was death. ResultsWe identified 120 patients. Mean age at the first visit was 32.2 years. Mean follow-up was 7.1 years. Fifty-five patients (45.8%) were assigned to G1, 30 (25%) to G2, and 35 (29.2%) to G3. Patients in G3 had worse renal function, functional class, and ejection fraction at the first visit and a more marked ejection fraction decline during follow-up, especially when compared with G1. Twenty-four patients (20%) died, 38 (31.7%) were admitted for heart failure, and 21 (17.5%) had atrial flutter/fibrillation during follow-up. These events were more frequent in G3 and significant differences were found compared with G1 in terms of death (HR, 2.9; 95%CI, 1.14-7.37; P=.026) and atrial flutter/fibrillation (HR, 2.9; 95%CI, 1.11-7.68; P=.037). ConclusionsThe type of palliation in patients with SVP and restricted pulmonary flow not undergoing Fontan palliation identifies distinct profiles. Patients palliated with aortopulmonary shunts have an overall worse prognosis with higher morbidity and mortality.

Mechanisms Limiting Renal Tissue Protection and Repair in Glomerulonephritis.

Glomerulonephritis are renal disorders resulting from different pathogenic mechanisms (i.e., autoimmunity, complement, inflammatory activation, etc.). Clarifying details of the pathogenic cascade is basic to limit the progression from starting inflammation to degenerative stages. The balance between tissue injury, activation of protective systems and renal tissue repair determines the final outcome. Induction of an oxidative stress is part of glomerular inflammation and activation of protective antioxidant systems has a crucial role in reducing tissue effects. The generation of highly reactive oxygen species can be evaluated in vivo by tracing the inner-layer content of phosphatidyl ethanolamine and phosphatidyl serine in cell membranes. Albumin is the major antioxidant in serum and the level of oxidized albumin is another indirect sign of oxidative stress. Studies performed in Gn, specifically in FSGS, showed a high degree of oxidation in most contexts. High levels of circulating anti-SOD2 antibodies, limiting the detoxyfing activity of SOD2, have been detected in autoimmune Gn(lupus nephritis and membranous nephropathy) in association with persistence of proteinuria and worsening of renal function. In renal transplant, high levels of circulating anti-Glutathione S-transferase antibodies have been correlated with chronic antibody rejection and progressive loss of renal function. Annexins, mainly ANXA1 and ANXA2, play a general anti-inflammatory effect by inhibiting neutrophil functions. Cytosolic ANXA1 is decreased in apoptotic neutrophils of patients with glomerular polyangitis in association with delayed apoptosis that is considered the mechanism for polyangitis. High circulating levels of anti-ANXA1 and anti-ANXA2 antibodies characterize lupus nephritis implying a reduced anti-inflammatory effect. High circulating levels of antibodies targeting Macrophages (anti-FMNL1) have been detected in Gn in association with proteinuria. They potentially modify the intra-glomerular presence of protective macrophages (M2a, M2c) thus acting on the composition of renal infiltrate and on tissue repair.