Furosemide Equivalent Dose Research Articles

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.

Congestion as a crucial factor determining albuminuria in patients with cardiorenal disease.

Albuminuria could potentially emerge as a novel marker of congestion in acute heart failure. However, the current evidence linking albuminuria and congestion in patients with congestive heart failure (CHF) remains somewhat scarce. This study aimed to evaluate the prevalence of albuminuria in a cohort of patients with CHF, identify the independent factors associated with albuminuria and analyse the correlation with different congestion parameters. This is a subanalysis of the Spanish Cardiorenal Registry, in which we enrolled 864 outpatients with heart failure and a value of urinary albumin:creatinine ratio (UACR) at the first visit. The median age was 74years, 549 (63.5%) were male and 438 (50.7%) had a reduced left ventricular ejection fraction. A total of 350 patients (40.5%) had albuminuria. Among these patients, 386 (33.1%) had a UACR of 30-300mg/g and 64 (7.4%) had a UACR >300mg/g. In order of importance, the independent variables associated with higher UACR were estimated glomerular filtration rate determined by the Chronic Kidney Disease Epidemiology Collaboration equation (R2=57.6%), systolic blood pressure (R2=21.1%), previous furosemide equivalent dose (FED; R2=7.5%), antigen carbohydrate 125 (CA125; R2=6.1%), diabetes mellitus (R2=5.6%) and oedema (R2=1.9%). The combined influence of oedema, elevated CA125 levels and the FED accounted for 15.5% of the model's variability. In patients with chronic stable heart failure, the prevalence of albuminuria is high. The risk factors of albuminuria in this population are chronic kidney disease and hypertension. Congestion parameters are also associated with increased albuminuria.

Loop diuretic down-titration at discharge in patients hospitalized for acute heart failure.

The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P=0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission.

Short-term outcomes after sodium-glucose cotransporter-2 inhibitor initiation in a cohort of heart failure patients.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) decrease mortality and risk of hospitalization in patients with heart failure with reduced ejection fraction (HFrEF). SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate rates of acute kidney injury (AKI) and therapy discontinuation with SGLT2i initiation in a real-world cohort of HFrEF patients. We abstracted data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting at the University of Michigan (between 1 July 2016 and 2 July 2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. A total of 200 patients were included. The majority of patients were male (64%) with a mean left ventricular ejection fraction (LVEF) of 27%. One hundred and four (52%) patients had diabetes mellitus. Most patients exhibited New York Heart Association class II (51.5%) or III (33.5%) symptoms. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3mg. AKI occurred in 22 patients and 18 patients discontinued their SGLT2i. Yeast infection (n=6), hypotension (n=5), and AKI (n=4) were the most common reasons for discontinuation. Using receiver operating characteristic curve analysis, the strongest models for AKI were A1C [area underneath its curve (AUC)=75.8, empirical confidence interval (ECI) 66.5-83.5]; baseline serum creatinine (SCr) (AUC=72.0, ECI 65.7-78.7); LVEF (AUC=67.6, ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC=66.0, ECI 57.5-74.6). Similarly, the strongest positive models for SGLT2i discontinuation were A1C (AUC=81.1, ECI 74.8-87.2); baseline SCr (AUC=67.4, ECI 58.7-75.5); LVEF (AUC=68.7, ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC=67.2, ECI 58.2-76.0). A1C was the strongest model of AKI, and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. Patients with higher baseline SCr on higher doses of loop diuretics may be at greater risk of these outcomes. Future prospective studies will be needed to further evaluate these findings and other models of AKI and SGLT2i discontinuation to guide clinical use of SGLT2 inhibitors.

Sacubitril/Valsartan Does Not Change the Use and Dose of Loop Diuretics in Patients With Heart Failure With Reduced Ejection Fraction

Background: There is no standard approach for managing the use or dose of loop diuretics after initiating sacubitril/valsartan. Objective: To investigate longitudinal trends in loop diuretic therapy use and doses during the initial 6 months following sacubitril/valsartan initiation. Methods: This retrospective cohort study included adult patients who were initiated on sacubitril/valsartan in cardiology clinics. Inclusion criteria were patients diagnosed with heart failure with reduced ejection fraction (ejection fraction ≤40%) and initiated on sacubitril/valsartan in an outpatient setting. We investigated longitudinal trends in the prevalence of loop diuretic use and furosemide equivalent dose at baseline, 2 weeks, 1 month, 3 month and 6 months following sacubitril/valsartan initiation. Results: A total of 427 patients were included in the final cohort. Compared to the baseline loop diuretic use and dose, there were no significant longitudinal changes in the prevalence of loop diuretic use or the furosemide equivalent dose over the 6 months following sacubitril/valsartan initiation. The use of sacubitril/valsartan was not significantly associated with reductions in the use or dose of loop diuretics over a 6-month follow-up period. Conclusion: The use of sacubitril/valsartan did not significantly change the use or dose of loop diuretics over 6-month follow-up period. Initiation of sacubitril/valsartan may not need a pre-emptive loop diuretic dose reduction.

Effect of eplerenone on clinical stability of Japanese patients with acute heart failure

BackgroundIn the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF) hospitalizations or all-cause mortality in 300 patients admitted for acute HF (AHF). However, the trial might have been underpowered for these endpoints, and a comprehensive overview of the effect of eplerenone on diuretic doses and patients' clinical stability is warranted. MethodsThe EARLIER trial included Japanese patients hospitalized for AHF randomly assigned to eplerenone or placebo over 6 months. Cox proportional hazards and mixed-effects models were used for analyses. ResultsThree hundred patients were included (mean age, 67 ± 13 years; 73% males). The median furosemide equivalent dose was 40 (20–62) mg at randomization. Patients with higher furosemide-equivalent doses had more severe signs and symptoms of congestion and a higher risk of all-cause mortality or HF hospitalization during 6-month follow-up (adjusted-hazard ratio per 10 mg/day increase = 1.25, 95% confidence interval: 1.05–1.49). Eplerenone significantly decreased furosemide-equivalent diuretic doses and b-type natriuretic levels throughout the follow-up (overall-joint-p < 0.05 for both) and reduced E/e' and inferior vena cava diameter at 4 weeks (both p < 0.05). Additionally, eplerenone significantly reduced left ventricular (LV) end-diastolic diameter at 24 weeks (p < 0.05). ConclusionsEplerenone treatment improved the clinical stability particularly during short period following hospitalization for AHF, translated by lower diuretic doses, natriuretic peptide levels, indirect markers of filling pressure and venous congestion, and a smaller LV volume.

115 DIURETIC DOSE TRAJECTORIES IN DILATED CARDIOMYOPATHY: PROGNOSTIC IMPLICATIONS

Abstract Background For patients with heart failure, prescription of loop diuretics (LD) and higher doses are associated with adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM). Methods Associations between outcomes and both furosemide equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were divided in i) dose↑ (FED increase by ≥50% or newly initiated); ii) dose↓ (FED decrease by ≥50%); iii) stable dose (change in FED by &amp;lt;50%); iv) never-users. Primary outcome was all-cause-death/heart transplantation/ventricular-assist-device/heart failure hospitalization. Secondary outcome was all-cause-death/heart transplantation/ventricular-assist-device. Results Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20mg increase: 1.12 [95% CI 1.04-1.22, p=0.003]. Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% dose↓; 26% stable dose and 14% dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of primary outcome (HR 2.42 [95% CI: 1.19-4.93], p=0.015), while dose↑ had the worst prognosis (HR 2.76 [95% C.I. 1.27-6.03], p=0.011). The results were consistent for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with improved outcome (HR 0.43 [95% C.I. 0.28-0.65], p&amp;lt;0.001). Conclusions In a large cohort of patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never require LD have an excellent prognosis.

CHAnges in Diuretic Medication Prescribing and Surrogate Laboratory Parameters After Initiating EmpagliflOziN in Veterans (CHAMPION Cohort Study).

Sodium-glucose cotransporter type 2 inhibitors have evolved into a novel drug class utilized for reductions in cardiovascular risk and heart failure hospitalization. We aimed to describe the impact of sodium-glucose cotransporter type 2 inhibitors on diuretic prescribing patterns and intermediate laboratory outcomes in patients with and without diuretic use. This retrospective cohort study included patients taking empagliflozin as of 1 July, 2021. Patients were assigned to the intervention group if prescribed a diuretic concomitantly or a control group otherwise. The primary outcome was the impact of empagliflozin on diuretic prescribing (i.e., no change, discontinuation, decrease, increase). Secondary outcomes were change in weight, hemoglobin A1c, estimated glomerular filtration rate, hemoglobin, hematocrit, blood pressure, and electrolytes at 90 and 180 days. Mean differences were compared using the t-test between groups or the paired t-test within groups. Patients without diuretic use were matched 1:1 to patients taking diuretics using propensity scores. This study included 1189 patients: 750 in the control group and 439 in the intervention group. After propensity score matching, baseline characteristics were well balanced. Of the 439 patients in the intervention group, 118 had changes in the diuretic regimen. There were 131 changes: 109 (83.2%) discontinuations, 13 (9.92%) decreases, and nine (6.87%) increases. The mean furosemide equivalent loop dose was reduced after empagliflozin initiation (50.62 mg vs 43.13 mg; p < 0.001). Among all patients, there was a decrease in weight (p = 0.01), estimated glomerular filtration rate (p < 0.001), and hemoglobin A1c (p < 0.001). There was an increase in hemoglobin (p < 0.001), hematocrit (p < 0.001), and magnesium (p < 0.001). In the propensity score-matched cohort, there was a significant reduction from baseline in mean weight in the intervention group compared with the control group (p < 0.001). This hypothesis-generating study suggests that sodium-glucose cotransporter type 2 inhibitors may lower diuretic requirements, further supported by a reduction in weight in the intervention cohort.

Diuretic dose trajectories in dilated cardiomyopathy: prognostic implications

BackgroundFor patients with heart failure, prescription of loop diuretics (LD) and of higher doses are associated with an adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM).MethodsAssociations between outcomes and both furosemide-equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were classified as (i) dose↑ (FED increase by ≥ 50% or newly initiated); (ii) dose↓ (FED decrease by ≥ 50%); (iii) stable dose (change in FED by < 50%); and (iv) never-users. The primary outcome was all-cause-death/heart transplantation/ventricular-assist-device/heart failure hospitalization. The secondary outcome was all-cause-death/heart transplantation/ventricular-assist-device.ResultsOf 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22], p = 0.003).Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% were dose↓; 26% were stable dose and 14% were dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of the primary outcome (HR 2.42 [95% CI 1.19–4.93], p = 0.015), while dose↑ had the worst prognosis (HR 2.76 [95% CI 1.27–6.03], p = 0.011). Results were similar for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with an improved outcome (HR 0.43 [95% CI 0.28–0.65], p < 0.001).ConclusionsIn patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never receive LD have an excellent prognosis.Graphical abstractAmong 1131 DCM patients 65% received loop diuretics at enrolment (upper left side). The bar chart on the upper right side shows the categorization in never-users/ dose↓/stable dose/ dose↑ over 24 months of follow-up. At the bottom is reported on the left side of each panel (observation period) the trajectory of LD dose in the four groups (left panel) and in patients who have their LD suspended vs those who continue LD (right panel) in the first two years. On the right side of each panel is shown the incidence of primary outcomes during the subsequent follow-up in the subgroups (outcome assessment)

Abstract 13593: Rates of Acute Kidney Injury or Discontinuation After SGLT2 Inhibitor Initiation in a Real-World Cohort of Patients With Heart Failure With Reduced Ejection Fraction

Background: SGLT2 inhibitors (SGLT2i) decrease mortality and risk of hospitalizations in patients with HFrEF. SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate real-world rates of acute kidney injury (AKI) in our clinical setting that includes patients concurrently receiving high doses of loop diuretics. Methods: We abstracted patient level data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting in the University of Michigan (1/7/2016 - 2/7/2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. Secondary end points consisted of diuretic dose reduction, change in potassium, change in serum creatinine (SCr), and other side effects not requiring discontinuation. Results: The majority of patients were male (64%) with a mean LVEF of 27%. A total of 104 (52%) patients had diabetes mellitus. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3 mg. Twenty-two (11%) patients had AKI and 18 patients (9%) discontinued their SGLT2i. Yeast infection (3%), hypotension (2.5%), and AKI (2%) were the most common reasons for discontinuation. Using ROC curve analysis, the strongest predictors for AKI were A1C (AUC = 75.8, empirical confidence interval [ECI] 66.5-83.5); baseline SCr (AUC = 72.0 ECI 65.7-78.7); LVEF (AUC = 67.6 ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC = 66.0 ECI 57.5-74.6). Similarly, the strongest positive predictors for SGLT2i discontinuation were A1C (AUC = 81.1 ECI 74.8-87.2); baseline Scr (AUC = 67.4 ECI 58.7-75.5); LVEF (AUC = 68.7 ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC = 67.2 ECI 58.2-76.0). Conclusions: A1C was the strongest predictor of AKI and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. SCr, LVEF, and furosemide equivalents also predicted these outcomes.

Evaluating The Concomitant Therapy Of Sacubitril/ Valsartan And Loop Diuretics In Heart Failure With Reduced Ejection Fraction

<h3>Introduction</h3> The landmark trial for sacubitril/valsartan also showed that about 80% of patients with heart failure receiving sacubitril/ valsartan are on loop diuretic therapy. However, both sacubitril and loop diuretic have diuretic effects and the concomitant therapy of sacubitril/valsartan and loop diuretic therapy may cause over-diuresis which in turn, may cause an increased event rate of hypotension or acute kidney injury. However, no guideline addresses how to manage loop diuretic therapies/doses after initiating sacubitril/ valsartan because of the very limited data available. The primary objective was to investigate the longitudinal trend in loop diuretic therapy use and doses over the initial 6 months after sacubitril/valsartan initiation. The secondary objective was to quantify the effect of loop diuretic dose reduction on the event rate of over-diuresis over 6 months. <h3>Methods</h3> The retrospective cohort study included outpatients who are initiated on sacubitril/valsartan from January 1, 2015 to February 28, 2020. Inclusion criteria were patients aged greater than 18 years old receiving bumetanide, furosemide or torsemide, diagnosed as heart failure with reduced ejection fraction (ejection fraction ≤ 40%), and initiated on sacubitril/ valsartan in outpatient setting at any WVU system institution. For the primary objective, authors investigated the longitudinal trend in the prevalence of loop diuretic use and furosemide equivalent dose at baseline, 2 weeks, 1 month, 3 month and 6 months after sacubitril/ valsartan initiation. For the secondary objective, the primary outcome was the composite event rate of acute kidney injury or hypotension. The secondary outcomes include an individual outcome of acute kidney injury or hypotension. <h3>Results</h3> A total of 427 patients were included for the primary objective. Compared to the baseline loop diuretic use and dose, there was no significant change in longitudinal trend in the prevalence of loop diuretic use and furosemide equivalent dose at baseline, 2 weeks, 1 month, 3 month and 6 months after sacubitril/ valsartan initiation. For the secondary objective, there was no significant difference in hypotension (9.85 vs. 13.04%, p=0.523), AKI (10.95 vs. 17.39%, p=0.233) and the composite of hypotension or AKI (20.44 vs. 28.26%, p=0.245) between the loop diuretic home dose continuation (n=274) and dose reduction groups (n=46). Multivariate logistic regression analysis showed no significant differences in hypotension (OR 0.879, 95% CI 0.168, 4.594), AKI (OR 1.488, 95% CI 0.462, 4.797), and the composite of hypotension or AKI (OR 1.427, 95% CI 0.504, 4.041). <h3>Conclusions</h3> The use of sacubitril/valsartan was not associated with reduced use or dose of loop diuretic therapy over 6 months. The loop diuretic dose reduction approach was not associated with a reduced event rate of over-diuresis compared to the home dose continuation approach.

85 Diuretics trajectories in dilated cardiomyopathy

Abstract Aims Diuretics in heart failure (HF) are commended to relieve symptoms at lowest dosage effective. Dilated cardiomyopathy (DCM) is a particular HF setting with several variables that may influence disease trajectory. We aimed to assess the long-term use of diuretics in DCM, the possibility of withdrawal and to explore the prognostic correlations. Methods and results All consecutive DCM patients enrolled from 1990 to 2018 were considered eligible. All the patients had available the information about the furosemide-equivalent dose at baseline and at follow-up evaluation within 24 months. Patients were categorized in stable (diuretic dose variation &amp;lt;50%), increasers (diuretics dose increase ≥50% or initiation of diuretic therapy), and decreasers (diuretics dose decrease ≥50% or never prescribed diuretics in the 24-months observation period). The prognostic role of the diuretics trajectory group was assessed with Kaplan Meier analysis and with a time-dependent multivariable model. The outcome measure was a composite of all-cause death/heart transplantation/HF hospitalization (ACD/HTx/HFH). 908 patients were included [mean age 50 ± 16, 70% male sex, 24% NYHA class III or IV, mean left ventricular ejection fraction (LVEF) 31 ± 9%, 66% treated with diuretics at baseline]. The furosemide-equivalent dose at enrolment had a linear association with the risk of outcome. Compared to other groups, decreaser patients were younger, had less HF symptoms, higher LVEF and more dilated left atrium. Decreasers had a lower prescription rate of diuretics and less frequent indication to renin-angiotensin inhibitors and mineralocorticoid receptors antagonists. Over a median follow-up of 122 (62–195) months decreasers had the lowest incidence of outcome, followed by stable, while increasers had the worst outcome (P &amp;lt; 0.001). After adjustment for other prognosticators, compared to stable patients, decreasers had a reduced risk of ACD/HTx/HFH [HR: 0.497 (95% CI: 0.337–0.731)] while increasers had the highest risk of adverse outcome [HR: 2.027 (95% CI: 1.254–3.276)]. Similarly, amongst patients taking diuretics at baseline, the diuretics withdrawal was in independent outcome predictor. The only multivariable predictors of diuretics withdrawal were younger age and lower furosemide-equivalent dose at enrolment. Conclusions In DCM patients the diuretics dose at baseline is a strong prognosticator. Diuretics dose reduction or its withdrawal provides a prognostic benefit on hard outcome. Diuretics tapering in selected patients should be considered in the short-term follow-up to improve DCM prognosis.

Abstract 11860: Long Term Outcomes and Risk Stratification in Patients With Heart Failure With Recovered Ejection Fraction

Introduction: Data are lacking on the natural history of heart failure with recovered ejection fraction (HFrecEF) with no available risk model for future heart failure events. This study aimed to understand the long-term outcomes of patients with HFrecEF, identify predictors of adverse events, and develop a risk stratification model. Methods: From an academic healthcare system we retrospectively identified patients who had an improvement in left ventricular ejection fraction (LVEF) from &lt;40% to ≥53%. Significant predictors of all-cause mortality, hospitalization and recurrent reduction in LVEF were identified via Cox regression analysis. A Cox proportional hazard risk model was developed for all-cause mortality. Results: 133 patients were included (median age 67, 39% female, 30% ischemic etiology). Kaplan-Meier survival was 70% at 5 years. Freedom from hospitalization was 58% at 1 year, and the risk of recurrent LVEF reduction to &lt;40% was 28% at 3 years. Diuretic dose and BNP at the time of LVEF recovery were the strongest predictors of mortality and hospitalization in multivariate adjusted analysis (BNP HR per 100pg/mL increase 1.13 [p&lt;0.01]; furosemide equivalent dose HR per 40mg increase 1.19 [p=0.02]). An all-cause mortality risk model incorporating NYHA functional class, BNP and diuretic dose at the time of recovery showed excellent risk discrimination (c-statistic 0.79) and calibration. Conclusions: Patients with HFrecEF have significant heterogeneity in clinical outcomes ranging from persistent recovery to requiring advanced heart failure therapies or death. A risk model utilizing NYHA functional class, BNP and diuretic dose can accurately stratify mortality risk.

Association Between Adaptive Servo-Ventilation Therapy and Renal Function.

Cardio-renal syndrome is a challenging clinical entity to manage, and is often associated with increased morbidity and mortality. We hypothesized that adaptive servo-ventilation (ASV), non-invasive positive pressure ventilation that ameliorates systemic/pulmonary congestion, may improve renal function in patients with symptomatic heart failure complicated by the cardio-renal syndrome. Patients with symptomatic congestive heart failure who underwent ASV therapy for over 1 month were included in this retrospective study. The trajectory of the estimated glomerular filtration ratio (eGFR) between the pre-1 month period and the post-one-month period (on ASV) were compared. A total of 81 patients (median 65 years old, 65 men) were included. eGFR decreased during the pre-1 month period from 52.7 (41.7, 64.6) down to 49.9 (37.3, 63.5) mL/minute/1.73 m2 (P < 0.001) whereas we observed an increase following one-month of ASV therapy up to 53.4 (38.6, 68.6) mL/minute/1.73 m2 (P = 0.022). A reduction in furosemide equivalent dose following the initiation of ASV therapy was independently associated with increases in eGFR with an adjusted odds ratio of 13.72 (95% confidence interval 3.40-55.3, P < 0.001). In conclusion, short-term ASV therapy was associated with the preservation of renal function, particularly when the dose of loop diuretics was concomitantly reduced.

Diuretic therapy as prognostic enrichment factor for clinical trials in patients with heart failure with reduced ejection fraction.

Loop diuretics are the mainstay of congestion treatment in patients with heart failure (HF). We assessed the association between baseline loop diuretic use and outcome. We also compared the increment in risk related to diuretic dose with conventional prognostic enrichment criteria used in the EMPHASIS-HF trial, which included patients with systolic HF and mild symptoms, such as prior hospitalization and elevated natriuretic peptides. Individual analyses were performed according to baseline loop diuretic usage (furosemide-equivalent dose > 40mg, 1-40mg, and no furosemide), and according to enrichment criteria adopted in the trial [i.e. recent hospitalization (< 30days or 30 to 180days prior to randomization) due to HF or other cardiovascular cause, or elevated natriuretic peptides]. The primary endpoint was a composite of cardiovascular death or HF hospitalization. Loop diuretic usage at baseline (HR for > 40mg furosemide-equivalent dose = 3.16, 95% CI 2.43-4.11; HR for 1-40mg = 2.06, 95% CI 1.60-2.65) was significantly associated with a higher risk for the primary endpoint in a stepwise manner when compared to no baseline loop diuretic usage. In contrast, the differences in outcome rates were more modest when using history of hospitalization and/or BNP: all HR ranged from 1 (reference, non-HF related CV hospitalization > 30days) to 2.04 (HF hospitalization < 30days). The effect of eplerenone on the primary endpoint was consistent across subgroups in both analyses (P for interaction ≥ 0.2 for all). Loop diuretic usage (especially at doses > 40mg) identified patients at higher risk than history of HF hospitalization and/or high BNP blood concentrations.

Validation of Natriuretic Response Prediction Equation in Patients with Acute Decompensated Heart Failure

Introduction The majority of acute decompensated heart failure (ADHF) admissions are driven by congestion. Sodium is the primary pathophysiologic driver of volume retention, with water passively following. However, monitoring sodium output in routine clinical practice is challenging. We previously created a model, the natriuretic response prediction equation (NRPE), to predict total sodium excretion following an IV dose of loop diuretic. The NRPE requires only a spot urine sodium and creatinine obtained 2 hours following diuretic administration (Figure 1). The objective of this study was to externally validate the NRPE. Hypothesis NRPE will accurately predict 6 hour post loop diuretic sodium output. Methods A total of 638 urine collections from 409 patients hospitalized with ADHF undergoing intravenous loop diuretic therapy were included. Intensively supervised urine collections were performed, and urine spot samples were taken at 2 hours after loop diuretic administration. A poor natriuretic response was defined as a sodium output of 150 mmol within this 6-hour period. Results The median IV furosemide equivalent dose was 80 mg (40-160), resulting in a cumulative 6-hour sodium output of 85 mmol (50-143) and urine output of 960 mL (640-1410). Poor natriuretic response was observed in 25% of the urine collections, averaging a cumulative sodium output of 29±13 mmol. Suboptimal and excellent responses were seen in 57% and 21% of the visits. The NRPE accurately predicted poor, suboptimal, and excellent natriuretic response, with an AUC of 0.92, 0.90, and 0.90, respectively (p Conclusions The NRPE, using only a 2 hour post diuretic spot urine sample, is a rapid and highly accurate method to monitor natriuretic response in ADHF patients.

Baseline and incident hypochloremia in chronic heart failure outpatients: Clinical correlates and prognostic role

BackgroundElectrolyte serum disorders are associated with poor outcome in chronic heart failure. The aim of this study sought to identify the main driver of incident hypochloremia in chronic HF (CHF) outpatients and to determine the prognostic value of baseline and incident hypochloremia. MethodsConsecutive CHF outpatients were enrolled and clinical, laboratoristic and echocardiographic evaluations were performed at baseline and repeated yearly in a subgroup of patients. Baseline and incident hypochloremia were evaluated. During an up to 5-year follow-up, all-cause mortality was the primary end-point for outcome. ResultsAmong 506 patients enrolled, 120 patients died during follow-up. At baseline, hypochloremia was present in 10% of patients and it was associated with mortality at univariate (HR: 3.25; 95%CI: 2.04–5.18; p<0.001) and at multivariate analysis (HR 2.14; 95%CI: 1.23–3.63; p: 0.005) after correction for well-established CHF prognostic markers. Among patients with repeated evaluations and without baseline hypochloremia, in 13% of these, incident hypochloremia occurred during follow-up and furosemide equivalent daily dose was its first determinant (HR for 1 mg/die: 1.008; 95%CI: 1.004–1.013; p<0.001) at forward stepwise logistic regression analysis. Finally, incident hypochloremia was associated with mortality at univariate (HR: 4.69; 95%CI: 2.69–8.19; p<0.001) as well as at multivariate analysis (HR: 2.97; 95%CI: 1.48–5.94; p: 0.002). ConclusionsIn CHF outpatients baseline and incident hypochloremia are independently associated with all-cause mortality, thus highlighting the prognostic role of serum chloride levels which are generally unconsidered. Future studies should evaluate if the strict monitoring and correction of hypochloremia could exert a beneficial effect on prognosis.

Reduced Diuretic Dose in Patients Treated With Eplerenone: Data From the EPHESUS Trial.

Loop diuretics are used for congestion relief, and dose adaptations are usually a consequence of the clinicians' clinical judgement about the congestive status of the patient. In EPHESUS (Eplerenone in Patients With Systolic Dysfunction After Myocardial Infarction), many patients required diuretics for congestion relief. We thus hypothesized that blinded allocation to eplerenone would lead clinicians to reduce loop diuretics, as a consequence of the improvement in patients' status. Cox and mixed-effects models were used over a median follow-up of 1.3 years in 6632 patients. A total of 6632 patients were included; at baseline, 3352 (50.5%) did not have diuretics, 2195 (33.1%) had diuretic doses between 1 and 40 mg/day, and 1085 (16.4%) had diuretic doses >40 mg/day. Patients with higher furosemide equivalent doses had a worse clinical status. Both baseline and follow-up incremental loop diuretic doses were associated with worse prognosis. Eplerenone treatment was associated with lower prescribed loop diuretic doses throughout the follow-up; lower doses were observed at 90 days and decreased further at 180 days and beyond. Eplerenone treatment led to a mean furosemide equivalent dose reduction of -2.2 mg/day (-2.9 to -1.6) throughout the follow-up. Eplerenone was effective in reducing morbidity and mortality regardless of the baseline loop diuretic dose used: hazard ratio for the outcome of cardiovascular death or heart failure hospitalization was 0.83 ([95% CI, 0.75-0.92]; P for interaction, 0.54). Eplerenone treatment led to a loop diuretic dose reduction during follow-up without evidence of treatment effect modification by loop diuretics. These findings suggest that eplerenone reduces congestive signs and symptoms, which enables clinicians to reduce loop diuretic doses.

Angiotensin Receptor Neprilysin Inhibition in Patients with Left Ventricular Assist Devices

Angiotensin receptor neprilysin inhibitors (ARNI) are now an established therapy for HF pts. While LVADs are a life-prolonging treatment for advanced HF, optimal management of hypertension and HF in this population is not known. We sought to evaluate the safety and efficacy of ARNI therapy in LVAD pts. We retrospectively reviewed all LVAD pts implanted between 8/2010 and 5/2019 who were subsequently treated with ARNI for at least 3 months. The primary outcome was change in NT-proBNP between the time of ARNI initiation (t0) and at 3- and 6-mo follow up. Safety endpoints included changes in mean arterial blood pressure (MAP), serum creatinine and potassium pre- and post-ARNI therapy. Data on concomitant drug therapy including diuretic dosing equivalents were also gathered. The above mentioned variables were log-transformed prior to analysis with repeated measures ANOVA. Pairwise comparisons were performed with Bonferroni's post hoc test. 30 pts met our inclusion criteria (age 54.7 ± 15.5 y; 90% M; HM3 17[57%], HMII 12[40%], HVAD 1 [3%]). ARNI was initiated at a median of 250 [67 - 601] days after LVAD implant. Prior to ARNI initiation, 47% were on ACE inhibitor, 13% on ARB, 40% on neither and 60% were treated with diuretics, with an average oral furosemide equivalent dose of 34 mg/day. At t0, 73% were started on 24/26 mg, and at 6 mos, 27% were on 49/51 mg and 32% on 97/103 mg of ARNI (Table). There was no statistically significant change in median MAP, serum creatinine or potassium (Table). A significant decrease in NT-proBNP was noted from t0 to follow-up (t0 = 1082 pg/mL, 3 mos = 724 pg/mL, 6 mos = 651 pg/mL) (Figure). The use of ARNI therapy was well tolerated among LVAD pts. There was a significant decrease in NT-proBNP levels, an effect previously reported in HF pts without LVADs in the PARADIGM-HF and PIONEER-HF trials. Randomized studies to determine the role of ARNI on the clinical course of LVAD patients are warranted.

CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction

BackgroundThe optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. MethodsThis multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. ResultsThe mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). ConclusionA CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction.