Diuretic Resistance In Heart Failure Research Articles

Combinational Diuretics in Heart Failure.

Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a consequence of nephron remodelling, and the combination of diuretics will be necessary to improve diuretic response and achieve decongestion. This review integrates data from recent research and offers a practical approach to current pharmacologic therapies to manage congestion in HF with a focus on combinational therapy. Until recently, combined diuretic treatment was based on observational studies and expert opinion. Recent evidence from clinical trials has shown that combined diuretic treatment can be started earlier without escalating the doses of loop diuretics with an adequate safety profile. Diuretic combination is a promising strategy for overcoming diuretic resistance in HF. Further studies aiming to get more insights into the pathophysiology of diuretic resistance and large clinical trials confirming the safety and efficacy over standard diuretics regimens are warranted.

The Role of Sodium-Glucose Co-Transporter-2 Inhibitors on Diuretic Resistance in Heart Failure.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Recently, significant advances have been made in its treatment; however, diuretics remain the cornerstone in managing congestion in HF. Although diuretic resistance poses a significant challenge in the management of HF and is associated with poor outcomes, only limited alternative pharmaceutical options are available in clinical practice. The objective of this narrative review is to provide a comprehensive analysis of the current evidence on the effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on diuretic resistance in HF patients. The primary emphasis is placed on clinical data that assess the impact of SGLT-2 inhibitors on fluid balance, symptom improvement, and clinical outcomes and secondarily on safety profile and potential adverse effects associated with SGLT-2 inhibitor use in acute decompensated HF. The current evidence on the efficacy of SGLT-2 on diuretic resistance remains controversial. Findings from observational and randomized studies are quite heterogenous; however, they converge on the notion that although SGLT-2 inhibitors show promise for mitigating diuretic resistance in HF, their diuretic effect may not be potent enough to be widely used to relieve objective signs of congestion in patients with HF. Importantly, the introduction of SGLT-2 inhibitors in HF treatment appears to be generally well tolerated, with manageable adverse effects. Further research is needed to investigate the underlying mechanisms and the possible beneficial impact of SGLT-2 inhibitors on diuretic resistance in HF.

Cutting the Gordian Knot of Diuretic Resistance in Heart Failure; Combination of Continuous Ultrafiltration with Diuretic Therapy

Cutting the Gordian Knot of Diuretic Resistance in Heart Failure; Combination of Continuous Ultrafiltration with Diuretic Therapy

The Importance of the Nephrologist in the Treatment of the Diuretic-Resistant Heart Failure.

Heart failure is not only a global problem but also significantly limits the life prospects of these patients. The epidemiology and presentation of heart failure are intensively researched topics in cardiology. The risk factors leading to heart failure are well known; however, the real challenge is to provide effective treatments. A vicious cycle develops in heart failure of all etiologies, sooner or later compromising both cardiac and kidney functions simultaneously. This can explain the repeated hospital admissions due to decompensation and the significantly reduced quality of life. Moreover, diuretic-refractory heart failure represents a distinct challenge due to repeated hospital admissions and increased mortality. In our narrative review, we wanted to draw attention to nephrology treatment options for severe diuretic-resistant heart failure. The incremental value of peritoneal dialysis in severe heart failure and the feasibility of percutaneous peritoneal dialysis catheter insertion have been well known for many years. In contrast, the science and narrative of acute peritoneal dialysis in diuretic-resistant heart failure remains underrepresented. We believe that nephrologists are uniquely positioned to help these patients by providing acute peritoneal dialysis to reduce hospitalization dependency and increase their quality of life.

A second-generation artificial intelligence-based therapeutic regimen improves diuretic resistance in heart failure: Results of a feasibility open-labeled clinical trial

IntroductionDiuretics are a mainstay therapy for congestive heart failure (CHF); however, over one-third of patients develop diuretic resistance. Second-generation artificial intelligence (AI) systems introduce variability into treatment regimens to overcome the compensatory mechanisms underlying the loss of effectiveness of diuretics. This open-labeled, proof-of-concept clinical trial sought to investigate the ability to improve diuretic resistance by implementing algorithm-controlled therapeutic regimens. MethodsTen CHF patients with diuretic resistance were enrolled in an open-labeled trial where the Altus Care™ app managed diuretics' dosage and administration times. The app provides a personalized therapeutic regimen creating variability in dosages and administration times within pre-defined ranges. Response to therapy was measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-minute walk test (SMW), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and renal function. ResultsThe second-generation, AI-based, personalized regimen alleviated diuretic resistance. All evaluable patients demonstrated clinical improvement within ten weeks of intervention. A dose reduction (based on a three-week average before and last three weeks of intervention) was achieved in 7/10 patients (70 %, p = 0.042). The KCCQ score improved in 9/10 (90 %, p = 0.002), the SMW improved in 9/9 (100 %, p = 0.006), NT-proBNP was decreased in 7/10 (70 %, p = 0.02), and serum creatinine was decreased in 6/10 (60 %, p = 0.05). The intervention was associated with reduced number of emergency room visits and the number of CHF-associated hospitalizations. SummaryThe results support that the randomization of diuretic regimens guided by a second-generation personalized AI algorithm improves the response to diuretic therapy. Prospective controlled studies are needed to confirm these findings.

Effectiveness of Zhuling decoction on diuretic resistance in patients with heart failure: a randomized, controlled trial.

To test the effects of Zhuling decoction on patients with diuretic resistance in heart failure compared with a group of patients undergoing conventional treatment alone. This research was a prospective, randomized, controlled study. From July 2018 to August 2020, 96 diuretic resistance patients from the Cardiovascular Research Center of Taicang Hospital affiliated with Nanjing University of Traditional Chinese Medicine (Grade III Hospital of Traditional Chinese Medicine) were enrolled in the study. The subjects were randomly divided into an observation group (48 cases) and a control group (48 cases). Patients in both groups received conventional treatment. In addition, observation group patients received Traditional Chinese Medicine Zhuling decoction. The primary endpoint was the urine output mean difference between Day 1 and Day 7 after treatment. Secondary endpoints were the changes over time in the N-terminal pro-B type natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) functional classification, and Minnesota Living with Heart Failure Questionnaire (MLHFQ). The safety and tolerability of the drug were comprehensively evaluated based on adverse drug reactions, as well as laboratory-assisted tests for liver and kidney function and electrolytes. Significant improvements were demonstrated for urine output in the two groups at Day 7, with a 1325 1045 mL difference in favor of the observation group ( = 0.018). The observation group also had greater improvements in NT-proBNP and NYHA functional classification changes than the control group. At the 30th day of follow-up, a significant reduction in negative findings on the MLHFQ from baseline was observed in both groups, but the observation group demonstrated a significantly greater reduction than the control group ( <0.001). Zhuling decoction could be used in combination therapy for patients with diuretic resistance in heart failure in addition to standard treatment.

Is peritoneal dialysis an effective treatment for cardiorenal syndrome with decompensated heart failure? A single center experience

Introduction and Objectives: ultrafiltration techniques have shown promise in the treatment of diuretic-resistant heart failure (HF). The aim of this study was to describe a center experience in treating refractory HF with peritoneal dialysis (PD). Methods: we performed a retrospective study of 14 patients presenting symptoms and signs of refractory congestive HF despite optimal pharmacological therapy, all excluded as candidates for heart transplantation. Baseline characteristics, laboratory data, Charlson score, and transthoracic doppler-echocardiogram results were collected. PD adequacy was evaluated through peritoneal equilibrium test results. Results: 12 patients were males and 2 females, with a median age of 72.13 years. The mean following time was 52.5 months. Symptoms of HF improved in 5 patients, with an upgrade of New York Heart Association (NYHA) Functional Classification and improvement in ejection fraction. NHYA remained the same in 6 PD treated individuals, despite and improvement of absolute ejection fraction. At the beginning of PD, the mean Charlson Score value was 5.7 ± 2.3, which reduced to 5.3 ± 2.6 by the end of observation time (p&lt;0.01; r=0.984). Six patients presented one episode of decompensated heart failure needing hospitalization, with a median length of stay of 2 days. During the observation period 2 patients died, 1 from an acute hemorrhagic stroke and the other with a septic shock. Discussion: PD treatment in refractory HF seems to be effective since it improves quality of life and functional class.

Hypertonic Saline For The Treatment of Diuretic Resistance In Advanced Heart Failure: A Retrospective Analysis From The Cleveland Clinic

Background Recent studies demonstrated that intravenous hypertonic saline solution (HSS) in combination with high-dose furosemide for the management of diuretic resistance in heart failure can lead to improved diuresis, reduction in length of hospitalization and mortality. Objective The objective of this study was to analyze real world use and safety of HSS administration in advanced heart failure patients in the Cleveland Clinic and identify factors for improvement for the development of an institutional protocol. Methods A retrospective chart analysis was performed in all advanced heart failure patients in whom HSS was administer and who were admitted to the intensive heart failure care unit from 2008 to 2019. Results In our study cohort of 34 patients who received HSS (median age 64 [IQR 53,68] years, 56% male, median LVEF 23 [IQR 15,39]%, median Cr 1.4 [IQR 1.1,2.1]mg/dL, median Na 121 [IQR 116,125]mg/dL), all subjects except one received 3% sodium chloride as HSS regimen. There was large variability in amount of NaCl administered (median 5,5 [IQR 3.4,18]g), infusion speed (median 50 [25,71]ml/min) and concurrent intravenous administration of loop diuretics (75%) and their dosages (furosemide median dose 240 [100-490]mg). The change in serum sodium serum sodium (3 [IQR 1, 5] mmol/L) after HSS was significant (p Conclusion Hypertonic saline solution administered has largely restricted to a relatively small cohort of end-stage heart failure patients with significant hyponatremia, and demonstrated increase in serum sodium without detrimental effects on renal function or complications related to sodium repletion or volume overload. However, the lack of a standardized precluded meaningful assessment of safety and efficacy of such interventions.

Aquapheresis: An Institutional Experience.

Aquapheresis (AQ) consists of the extracorporeal extraction of plasma water from the vascular space across a semipermeable membrane in response to a transmembrane pressure gradient. The primary utilization of AQ has been in the management of patients with diuretic resistant heart failure with a treatment goal directed to quickly eliminate the excess fluid and optimize volume status. This modality is similar to isolated ultrafiltration performed on those patients requiring dialysis, but utilizes a machine that is smaller and easier to initiate and operate compared with traditional dialysis equipment. A retrospective study that describes the indications in which AQ was utilized at Lenox Hill Hospital. The patient list was generated by searching for the keyword "Aquaph" in our electronic health record (EHR) orders. Patients were categorized based on hospital location and indication of AQ therapy. Additional information includes duration of treatment (days), changes in creatinine (start of AQ to stop of AQ), and total volume removed. The search generated 28 patients; five were excluded as AQ was not initiated. In the remaining 23 patients, the mean aquapheretic volume per day was 1954 mls, with no significant change in creatinine. Indications for AQ broke out into five main categories: cardiogenic shock including post cardiothoracic procedure (10 pts); anasarca (5 pts); ATN with volume overload (4 pts); ESKD with bridge ultrafiltration between hemodialysis treatments (2 pts); and post-op volume overload (2 pts). We found that aquapheresis can be utilized in situations other than diuretic resistant heart failure. Also to consider, is the ease in which this less complicated aquapheresis equipment can be operated compared to the more complex hemodialysis equipment.

The use of peritoneal dialysis in heart failure: A systematic review.

Heart failure (HF) is a major cause of morbidity and mortality. Extracorporeal (EC) therapy, including ultrafiltration (UF) and haemodialysis (HD), peritoneal dialysis (PD) and peritoneal ultrafiltration (PUF) are potential therapeutic options in diuretic-resistant states. This systematic review assessed outcomes of PD and compared the effects of PD to EC. A comprehensive search of major databases from 1966 to 2017 for studies utilising PD (or PUF) in diuretic-resistant HF was conducted, excluding studies involving patients with end-stage kidney disease. Data were extracted and combined using a random-effects model, expressed as odds ratio (OR). Thirty-one studies (n = 902) were identified from 3195 citations. None were randomised trials. Survival was variable (0-100%) with a wide follow-up duration (36 h-10 years). With follow-up > 1 year, the overall mortality was 48.3%. Only four studies compared PD with EC. Survival was 42.1% with PD and 45.0% with EC; the pooled effect did not favour either (OR 0.80; 95% confidence interval (CI): 0.24-2.69; p = 0.710). Studies on PD in patients with HF reported several benefits. Left ventricular ejection fraction (LVEF) improved after PD (OR 3.76, 95%CI: 2.24-5.27; p < 0.001). Seven of nine studies saw LVEF increase by > 10%. Twenty-one studies reported the New York Heart Association status and 40-100% of the patients improved by ≥ 1 grade. Nine of 10 studies reported reductions in hospitalisation frequency and/or duration. When treated with PD, HF patients had fewer symptoms, lower hospital admissions and duration compared to diuretic therapy. However, there is inadequate evidence comparing PD versus UF or HD. Further studies comparing these modalities in diuretic-resistant HF should be conducted.

Current approach to diuretic resistance in heart failure

Current approach to diuretic resistance in heart failure

Current Approach to Diuretic Resistance in Heart Failure

Current Approach to Diuretic Resistance in Heart Failure

Kidney Support in Children using an Ultrafiltration Device: A Multicenter, Retrospective Study.

Provision of kidney replacement therapy (KRT) to manage kidney injury and volume overload in critically ill neonates and small children is technically challenging. The use of machines designed for adult-sized patients, necessitates large catheters, a high extracorporeal volume relative to patient size, and need for blood priming. The Aquadex FlexFlow System (CHF Solutions Inc., Eden Prairie, MN) is an ultrafiltration device designed for fluid removal in adults with diuretic resistant heart failure. It has an extracorporeal volume of 33 ml, which can potentially mitigate some complications seen at onset of KRT in smaller infants. In this multicenter, retrospective case series of children who received KRT with an ultrafiltration device (n=119 admissions, 884 circuits), we report demographics, circuit characteristics, complications, and short- and long-term outcomes. Patients were grouped according to weight (<10, 10-20, and >20 kg), and received one of three modalities: slow continuous ultrafiltration, continuous venovenous hemofiltration (CVVH), or prolonged intermittent KRT. Our primary outcome was survival to end of KRT. Treatment patterns and outcomes varied between the groups. In patients who weighed <10 kg, the primary indication was AKI in 40%, volume overload in 46%, and ESKD in 14%. These patients primarily received CVVH (66%, n=48) and prolonged intermittent KRT (21%, n=15). In the group weighing >20 kg, volume overload was the primary indication in 91% and slow continuous ultrafiltration was the most common modality. Patients <10 kg had lower KRT survival than those >20 kg (60% versus 97%), more volume overload at onset, and received KRT for a longer duration. Cardiovascular complications at initiation were seen in 3% of treatments and none were severe. Complications during therapy were seen in 15% treatments and most were vascular access-related. We report the first pediatric experience using an ultrafiltration device to provide a range of therapies, including CVVH, prolonged intermittent KRT, and slow continuous ultrafiltration. We were able to initiate KRT with minimal complications, particularly in critically ill neonates. There is an unmet need for devices specifically designed for younger patients. Having size-appropriate machines will improve the care of smaller children who require kidney support.

Prevalence and outcome of diuretic resistance in heart failure.

Diuretic resistance (DR) is common in patients with decompensated heart failure (HF), and is associated with adverse outcomes. To determine the prevalence of DR and its impact on survival among patients with decompensated HF, we prospectively evaluated the prevalence and influence on prognosis of DR (defined as persistent congestion despite ≥ 80mg of furosemide per day) in a cohort of elderly patients from the Spanish HF registry (RICA) admitted for an acute decompensation of HF. Patients with new-onset HF were excluded. From the global cohort of 2067 patients, 435 (21%; 95% CI 19.3%-22.7%) patients met criteria for DR. Patients with DR had more comorbidities (hypercholesterolemia, diabetes mellitus, valvular disease, chronic kidney disease, and cancer) and a worse functional status compared to patients without DR. In addition, patients with DR had a higher proportion of ischemic etiology, more advanced functional class and lower left ventricular ejection fraction values. After 1year of follow-up, all-cause mortality was higher in patients with DR with an adjusted hazard ratio of 1.37 (95% CI 1.06-1.79; p = 0.018). The prevalence of DR in a cohort of elderly patients admitted for acute HF decompensation is 21%. DR is an independent predictor of 1-year mortality.

The Basic Metabolic Profile in Heart Failure-Marker and Modifier.

The physiologic determinants of each of the components of the basic metabolic profile in patients with heart failure will be explored. Additionally, the review will discuss the prognostic value of alterations in the basic metabolic profile as well as their effects on management. Abnormalities in the basic metabolic profile have significant correlation with clinical outcomes and can modify treatment in heart failure. Hypochloremia has recently received increased attention for these reasons. Elevated creatinine, increased blood urea nitrogen, hyponatremia, and hypochloremia correlate with worse mortality and diuretic resistance in heart failure. Hypokalemia, even when mild, has proven to be a worse clinical indicator than modest elevations in serum potassium. Hypochloremia is mechanistically linked to hyponatremia and metabolic alkalosis, but recent compelling data suggests that it can provide more discriminating prognostic information. Knowledge of the physiologic basis for each of these alterations informs their management.

030 - Potential Role for Plasmin Mediated Proteolytic Activation of ENaC in Diuretic Resistance in Heart Failure

Background: The amiloride sensitive Epithelial Na + channel (ENaC) plays a major role in regulation of sodium transport in the collecting duct of the kidney. Recent studies have shown that proteolytic cleavage of α and γ subunits by urinary proteases like plasmin play a major role in ENaC activation. Activation of ENaC in collecting tubules is thought to be an important mechanism driving renal Na + retention in several edematous disease states. Our aim was to probe if plasmin mediated ENaC activation is a potential mechanism of diuretic resistance in heart failure. Hypothesis: Increased urinary levels of plasminogen/plasmin will predict poor diuretic response in HF patients receiving loop diuretics. Methods: Heart failure outpatients in the Yale Transition Care Center treated with loop diuretics were prospectively studied (N = 131). Blood and urine chemistries were collected at baseline and at 1 to 1.5 hours post diuretic administration. Diuretic efficiency (DE) was defined as total sodium excreted per doubling of the diuretic dose. Total plasminogen was measured using the ELISA kit from Molecular Innovations (Novi, MI, USA). This assay kit measures both plasminogen and plasmin in biological fluids. Plasmin/plasminogen was indexed to urinary creatinine to correct for changes in urinary dilution. Results: The median dose of diuretic administered was 160 mg (40–280 mg) of furosemide equivalents, which resulted in an average of 987 ± 575 ml of urine and 97.4 ± 71.4 mmol of sodium output. There was good correlation between urinary plasminogen levels prior to and after administration of the loop diuretic (r = 0.74, P < .001), but interestingly plasmin levels increased by 190% ± 307% (P < .0001) with diuretic administration. Higher urinary plasminogen (indexed to urinary creatinine) levels at baseline were correlated with lower DE (r = −0.32, P = .001), as was the increase following administration of diuretics (r = −0.30, P = .004). In line with activation of ENaC, the fractional excretion of potassium at baseline (r = 0.26, P = .014) and post diuretic (r = 0.24, P = .012) was correlated with the corresponding urinary plasminogen concentration. Furthermore, the change in plasminogen was correlated with the post diuretic potassium to sodium ratio (a marker of distal tubular sodium/potassium exchange activity, r = 0.31, P = .002). Conclusion: In patients with heart failure receiving loop diuretics, urinary levels of plasmin/plasminogen were correlated with the degree of diuretic responsiveness and metrics of distal tubular potassium wasting. These hypothesis generating results suggest that ENaC activation via luminal plasmin may be a relevant and therapeutically modifiable target in HF. Additional research is warranted.

Management of Congestion and Diuretic Resistance in Heart Failure

We present the case of a patient with heart failure and severe congestion who was responding poorly to diuretic therapy. We discuss the key problems concerning the pathophysiology and bedside therapeutic approach to congestion and fluid overload in this clinical setting, and we give practical suggestions to overcome congestion, especially in the setting of diuretic resistance and worsening renal function. We conclude that the application of key pharmacokinetic and pharmacodynamic principles of diuretic therapy, along with in-depth knowledge of the pathophysiology of heart failure, still represent the cornerstones for a correct approach to decongestive therapy in these patients.

L'ultrafiltrazione Peritoneale Nello Scompenso Cardiaco: Dall'icodestrina Alla Classe NYHA

Abstract non disponibile (Cardionephrology)

Peritoneal Ultrafiltration and Heart Failure: from Icodextrin to NYHA Class

Is peritoneal ultrafiltration a useful therapeutic alternative in diuretic resistant heart failure, even in patients with preserved glomerular filtration rate?Some recent clinical trials, here briefly analysed, reported the positive effects of peritoneal ultrafiltration on NYHA class, hospitalization rates and quality of life of decompensated patients.Why this technique has so little fortune among Nephrologists?

Renal Dysfunction Has Limited Role in the Genesis of Diuretic Resistance in Heart Failure

Renal Dysfunction Has Limited Role in the Genesis of Diuretic Resistance in Heart Failure