Hyponatremia In Heart Failure Research Articles

Evaluation and Management of Hyponatremia in Heart Failure.

To provide a contemporary overview of the pathophysiology, evaluation, and treatment of hyponatremia in heart failure (HF). Potassium and magnesium losses due to poor nutritional intake and treatment with diuretics cause an intracellular sodium shift in HF that may contribute to hyponatremia. Impaired renal blood flow leading to a lower glomerular filtration rate and increased proximal tubular reabsorption lead to an impaired tubular flux through diluting distal segments of the nephron, compromising electrolyte-free water excretion. Hyponatremia in HF is typically a condition of impaired water excretion by the kidneys on a background of potassium and magnesium depletion. While those cations can and should be easily repleted, further treatment should mainly focus on improving the underlying HF and hemodynamics, while addressing congestion. For decongestive treatment, proximally acting diuretics such as sodium-glucose co-transporter-2 inhibitors, acetazolamide, and loop diuretics are the preferred options.

Effectiveness of urea administration for the treatment of hyponatremia in heart failure

ObjectivesTo assess the efficacy and safety of urea in patients with hyponatremia and heart failure (HF). Methods and resultsThis is a retrospective observational analytical study of patients with HF and hyponatremia (Na+ <135 mmol/l). Forty-nine patients treated with urea and 47 patients who did not receive urea, all under standard treatment (according to usual clinical practice) for HF, were included and followed up at Álvaro Cunqueiro Hospital in Vigo between January 2013 and May 2022. The study evaluated the normalization of sodium levels (Na > 135 mmol/l). The initial natremia at the start of oral urea treatment was 127 ± 5.22 mmol/l, at 24 h the sodium level was 128 ± 2.47 (p < 0.009), and the mean on the day of normalization was 135.19 ± 4.23 mmol/l (p < 0.005). The average number of days to achieve sodium normalization was 5.03 ± 2.37 days. The initial uremia at the start of urea treatment was 73 ± 46.93 mg/dl, and the mean on the day of Na + normalization was 116.05 ± 63.64 mg/dl (p < 0.002). The average oral urea dose was 22.5 g/day. No relevant adverse effects were observed, nor were there significant changes in creatinine levels. ConclusionsOral urea treatment, when added to standard treatment for short periods of time, is safe and effective in correcting natremia in patients with hypervolemic HF with hyponatremia.

Abstract 16169: Use of Ramen in Heart Failure: Correction of Severe Hyponatremia With Salt Intake

Background Hyponatremia (Na&lt;136mmol) is the most common electrolyte imbalance in patients with heart failure (HF) and is associated with increased mortality, morbidity and rehospitalizations. The mechanisms of hyponatremia in heart failure are multifold and include an increased sympathetic tone and renin-angiotensin-aldosterone-system, salt and water retention in the proximal and distal tubules, high antidiuretic hormone coupled low glomerular filtration rate and diuretic use. We present a case highlighting the complexity of sodium balance in acute decompensated heart failure. Case Presentation A 65-year-old female with a medical history of heart failure with preserved ejection fraction (EF 60-65%), pulmonary hypertension, atrial fibrillation, and CKD presented to the Emergency Department with volume overload. We began diuresis with bumetanide on hospital day 1 (HD#), however given inadequate urine output chlorthalidone was added on HD #5 and metolazone on HD #7. On admission, her sodium was 134 and down trended to a low of 121 on HD#13. She had worsening BUN/Cr from 62/2.14 at admission to a peak 135/2.66. She developed oral intake intolerance, asterixis and encephalopathy. The management changed to halting diuretics, fluid restriction, and hypertonic saline without improvement. Urine electrolytes were used to tailor treatment, leading to cessation of hypertonic saline stopped and introducing Ramen (875 mg of Na) and salt tablets (394 mg of Na). While maintaining euvolemia, there was resolution of symptoms and improvement in Na=134, BUN 49, Cr 1.16. Discussion Treatment options for hyponatremia in HF, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. The use of high oral salt intake with close monitoring of jugular vein pressure, weight, symptoms, and urine electrolytes can help a select group of patients with hyponatremia and advance heart failure despite traditional knowledge.

Salt Is Good: Correction of Hyponatremia in Heart Failure with Dietary Sodium

Salt Is Good: Correction of Hyponatremia in Heart Failure with Dietary Sodium

Management of Hyponatremia in Heart Failure: Practical Considerations.

Hyponatremia is commonly encountered in the setting of heart failure, especially in decompensated, fluid-overloaded patients. The pathophysiology of hyponatremia in patients with heart failure is complex, including numerous mechanisms: increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system, high levels of arginine vasopressin and diuretic use. Symptoms are usually mild but hyponatremic encephalopathy can occur if there is an acute decrease in serum sodium levels. It is crucial to differentiate between dilutional hyponatremia, where free water excretion should be promoted, and depletional hyponatremia, where administration of saline is needed. An inappropriate correction of hyponatremia may lead to osmotic demyelination syndrome which can cause severe neurological symptoms. Treatment options for hyponatremia in heart failure, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. The aim of this review is to summarize the principal mechanisms involved in the occurrence of hyponatremia, to present the main guidelines for the treatment of hyponatremia, and to collect and analyze data from studies which target new treatment options, such as vaptans.

Transcriptomic and metabolic profiling of Tolvaptan treated Autosomal dominant polycystic kidney disease (ADPKD) patient

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common and life‐threatening genetic kidney disease that characterized by the aberrant renal tubule epithelial cells proliferation leads to the formation of multiple fluid‐filled cysts, and most of the ADPKD patient will leads to kidney failure by age of 50. Currently, dialysis or a transplant are the only treatments for end‐stage ADPKD patients. Tolvaptan is a is a selective vasopressin V2‐receptor antagonist which was used to treat hyponatremia in heart failure but was approved by FDA for ADPKD treatment in 2018. However, there are limitations for ADPKD patients to receive Tolvaptan treatment and significant side effects severely affect patient’s life quality. In our study, a 34‐year‐old man was diagnosed with familial ADPKD. He had cysts in kidney (Mayo class 1c) and liver and showed no symptoms other than hypertension. His baseline eGFR was 76.98 ml/min/1.732mg/dL but declined to 57.02 ml/min/1.732mg/dL two years after his first diagnosis, and there was an increase in number and size of the cysts due to the rapidly progressive ADPKD. Tolvaptan was started with the 45‐0‐15 dose and the patient was well‐tolerated. After 60 days of treatment, the renal function dramatic improved (73.02 ml/min/1.732mg/dL). With the titrate to 60‐0‐30 dose of tolvaptan, his eGFR maintains above than 60 ml/min/1.732mg/dL more than 3 months until present.MethodInformation of transcriptome and metabolome has significantly contributed to identifying potential therapeutic targets for the management of diseases. In our study, we collect his blood and urine before Tolvaptan treatment and 2 and 3 months after Tolvaptan treatment for transcriptomic and metabolic profiling. Total RNA was extracted using Trizol® Reagent (Invitrogen, USA) according to the manual. cDNA libraries were prepared by SureSelect XT HS2 mRNA Library Preparation kit (Agilent, USA) and sequenced on Nextseq. Differential expression analysis was performed using StringTie and DEseq2 with genome bias detection/correction using Welgene Biotech's in‐house pipeline. Genes with p value &lt; 0.05 and &gt; 2.0‐fold changes were considered significantly differentially expressed, and functional enrichment assay in differentially expressed genes of each experiment design was performed using clusterProfiler v3.6.ResultsOur data indicates that tight junction proteins (Log2 ratio: CRB3, 11.01; CLDN10, 10.09; MAPK10, 7.34), cytoskeleton regulating proteins (Log2 ratio: FGF17, 9.47; MYH14, 7.04) which also genes involved in the regulation of calcium and MAPK signaling and following focal adhesion proteins were significantly (p&lt;0.05) preserved after 3 months Tolvaptan treatment. Furthermore, Hypoxanthine, Creatine, L‐a‐aminobutyric acid and Trimethylamine N‐oxide were significantly decreased in our metabolomics data analysis which is also indicates the inhibition of paracellular transportation in kidney epithelial/endothelial cells.ConclusionOur data indicates a potential molecular mechanism of Tolvaptan treatment in regulating the integrity of tight junction and kidney cells, and provides novel therapeutic targets in in ADPKD.

Updates and Perspectives on Aquaporin-2 and Water Balance Disorders.

Ensuring the proper amount of water inside the body is essential for survival. One of the key factors in the maintenance of body water balance is water reabsorption in the collecting ducts of the kidney, a process that is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and impermeable to ions or other small molecules. Impairments of AQP2 result in various water balance disorders, including nephrogenic diabetes insipidus (NDI), which is a disease characterized by a massive loss of water through the kidney and consequent severe dehydration. Dysregulation of AQP2 is also a cause of water retention with hyponatremia in heart failure, hepatic cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Antidiuretic hormone vasopressin is an upstream regulator of AQP2. Its binding to the vasopressin V2 receptor promotes AQP2 targeting to the apical membrane and thus enables water reabsorption. Tolvaptan, a vasopressin V2 receptor antagonist, is effective and widely used for water retention with hyponatremia. However, there are no studies showing improvement in hard outcomes or long-term prognosis. A possible reason is that vasopressin receptors have many downstream effects other than AQP2 function. It is expected that the development of drugs that directly target AQP2 may result in increased treatment specificity and effectiveness for water balance disorders. This review summarizes recent progress in studies of AQP2 and drug development challenges for water balance disorders.

OR30. Effect of hyponatremia in heart failure patients at discharge on 30-day readmission rate: a single-centre study

Abstract Background and Aims Hyponatremia is often observed in patients with heart failure. The proposed pathophysiology of hyponatremia in heart failure is due to increase of arginine vasopressin activity that elevates renal water reabsorption, thereby diluting sodium content in plasma. Hyponatremia has been identified as a factor that worsens heart failure patients' prognosis, including cardiovascular morbidity and mortality. Thus, this study was conducted to investigate the impact of hyponatremia in heart failure patients on rehospitalisation within thirty days. Methods and Results This is a single-centre prospective cohort study. A total of 205 acute decompensated heart failure patients admitted to National Cardiovascular Center Harapan Kita from July 2018 to March 2019 were included into the study. The study population was then divided into two groups based on predischarge sodium level. In this study, hyponatremia was defined as serum sodium level less than 135 mEq/l. Among the study population, 58 patients (28.3%) had hyponatremia at discharge. The data was analyzed using chi-square test. There were 19 patients who were readmitted within 30 days and 52.9% of them had hyponatremia at discharge. The effect of hyponatremic status at discharge to 30-day readmission rate was statistically significant (p = 0.03, OR = 3.19 95%CI 1.22-8.33). Conclusion Hyponatremia in heart failure patients at discharge is associated with increased risk of 30-day readmission.

Hyponatremia in heart failure: not just 135 to 145.

One of the most frequent in-hospital electrolyte disturbances is hyponatremia. Hyponatremia in heart failure (HF) is mainly associated with hypervolemia resulting from activation of baroreceptor-mediated hormones, such as arginine vasopressin (AVP), renin-angiotensin-aldosterone system, and catecholamines. Various electrolyte imbalance can occur as heart failure progress. The goal of this review was to outline the current literature on hyponatremia in HF patients.

Think FIRST to treat Dilutional Hyponatremia in Patients With Heart Failure

Patients with heart failure (HF) are at risk of developing hyponatremia due to retention of fluids which dilutes serum sodium. Studies have demonstrated that health care professionals have inadequate knowledge of managing hyponatremia in patients with HF. We created a mnemonic that provides nurse practitioners with an evidence-based approach to managing hyponatremia in HF. The “FIRST” mnemonic features 5 different treatment options: Fluid restriction, Induced diuresis, Received no specific treatment for hyponatremia, Saline (isotonic and hypertonic), and Tolvaptan.

Arginine vasopressin modulates electrical activity and calcium homeostasis in pulmonary vein cardiomyocytes

BackgroundAtrial fibrillation (AF) frequently coexists with congestive heart failure (HF) and arginine vasopressin (AVP) V1 receptor antagonists are used to treat hyponatremia in HF. However, the role of AVP in HF-induced AF still remains unclear. Pulmonary veins (PVs) are central in the genesis of AF. The purpose of this study was to determine if AVP is directly involved in the regulation of PV electrophysiological properties and calcium (Ca2+) homeostasis as well as the identification of the underlying mechanisms.MethodsPatch clamp, confocal microscopy with Fluo-3 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, Ca2+ homeostasis, and Ca2+ regulatory proteins in isolated rabbit single PV cardiomyocytes incubated with and without AVP (1 μM), OPC 21268 (0.1 μM, AVP V1 antagonist), or OPC 41061 (10 nM, AVP V2 antagonist) for 4–6 h.ResultsAVP (0.1 and 1 μM)-treated PV cardiomyocytes had a faster beating rate (108 to 152%) than the control cells. AVP (1 μM) treated PV cardiomyocytes had higher late sodium (Na+) and Na+/Ca2+ exchanger (NCX) currents than control PV cardiomyocytes. AVP (1 μM) treated PV cardiomyocytes had smaller Ca2+i transients, and sarcoplasmic reticulum (SR) Ca2+ content as well as higher Ca2+ leak. However, combined AVP (1 μM) and OPC 21268 (0.1 μM) treated PV cardiomyocytes had a slower PV beating rate, larger Ca2+i transients and SR Ca2+ content, smaller late Na+ and NCX currents than AVP (1 μM)-treated PV cardiomyocytes. Western blot experiments showed that AVP (1 μM) treated PV cardiomyocytes had higher expression of NCX and p-CaMKII, and a higher ratio of p-CaMKII/CaMKII.ConclusionsAVP increases PV arrhythmogenesis with dysregulated Ca2+ homeostasis through vasopressin V1 signaling.

Hyponatremia in Heart Failure: Pathogenesis and Management.

Hyponatremia is a very common electrolyte abnormality, associated with poor short- and long-term outcomes in patients with heart failure (HF). Two opposite processes can result in hyponatremia in this setting: Volume overload with dilutional hypervolemic hyponatremia from congestion, and hypovolemic hyponatremia from excessive use of natriuretics. These two conditions require different therapeutic approaches. While sodium in the form of normal saline can be lifesaving in the second case, the same treatment would exacerbate hyponatremia in the first case. Hypervolemic hyponatremia in HF patients is multifactorial and occurs mainly due to the persistent release of arginine vasopressin (AVP) in the setting of ineffective renal perfusion secondary to low cardiac output. Fluid restriction and loop diuretics remain mainstay treatments for hypervolemic/dilutional hyponatremia in patients with HF. In recent years, a few strategies, such as AVP antagonists (Tolvaptan, Conivaptan, and Lixivaptan), and hypertonic saline in addition to loop diuretics, have been proposed as potentially promising treatment options for this condition. This review aimed to summarize the current literature on pathogenesis and management of hyponatremia in patients with HF.

Hypervolemic Hyponatremia in Heart Failure.

Heart failure (HF) represents the most common cause of hypervolemic hyponatremia in current clinical practice. The presence of hyponatremia has been independently associated with worse outcomes in this patient population. The pathogenesis of hyponatremia in HF involves complex neurohormonal and cardio-renal interactions, including an increase in non osmotic secretion of arginine vasopressin (AVP) and insufficient tubular flow in the diluting segments of the nephron. The treatment of hyponatremia in HF involves decongestant therapy with diuretics, neurohormonal blockade and in certain occasions the use of AVP antagonists. The aim of this chapter is to summarize the pathophysiology, current evidence, and management recommendations for hyponatremia in patients with HF, with a specific focus on AVP homeostasis.

P5670Long-term prognostic value of discharge hyponatremia in heart failure with reduced, mid-range and preserved ejection fraction

P5670Long-term prognostic value of discharge hyponatremia in heart failure with reduced, mid-range and preserved ejection fraction

Short and long-term prognostic value of hyponatremia in heart failure with preserved ejection fraction versus reduced ejection fraction: An analysis of the Korean Acute Heart Failure registry

BackgroundHyponatremia is a well-known risk factor for worse outcomes in heart failure (HF) patients. The impact of hyponatremia according to the ejection fraction (EF) is unclear. We evaluated the prognostic value of hyponatremia according to HF type. Methods and resultsThe Korea Acute Heart Failure (KorAHF) registry consecutively enrolled 5625 patients. Hyponatremia was defined as serum sodium level<135mmol/L at hospital admission. HF with preserved and reduced ejection fraction were defined as an LVEF ≥50% and LVEF ≤40%, respectively.Among 5103 patients with available EF, 2088 (60%) had HFrEF, and 1284 (25%) had HFpEF. There was no difference in serum sodium level between the groups (HFrEF: 137.4±4.7mmol/L vs. HFpEF: 137.5±5.0mmol/L, P=0.710).Hyponatremic patients had higher in-hospital mortality or urgent heart transplantation in all (11.3% vs. 4.5%, P<0.001), in HFrEF (13.1% vs. 4.9%, P<0.001), and in HFpEF (6.0% vs. 1.9%, P<0.001).After adjustment for significant covariates, hyponatremia was associated with 1.5 fold increased risk for 1-year post-discharge death in the HFrEF group (HR, 1.52; 95% CI, 1.24–1.86), but not in the HFpEF group (HR, 1.16; 95% CI, 0.84–1.61). During admission, the sodium status changed in 22% of the patients and the discharge sodium status had greater prognostic value. ConclusionsHyponatremia is independent of HF type. Hyponatremia is a significant risk factor for adverse in-hospital outcomes; however its long-term prognostic value is only limited to patients with HFrEF, but not for those with HFpEF.

Prognostic Significance of Discharge Hyponatremia in Heart Failure Patients With Normal Admission Sodium (from the ESCAPE Trial)

Hyponatremia in acute decompensated heart failure (HF) is indicative of a poor prognosis and predicts morbidity and mortality. We explored the predictive utility of hyponatremia at the time of hospital discharge among HF patients with normal admission sodium (Na). Characteristics and outcomes of HF patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial, who had normal Na on admission, were compared between those who were hyponatremic (Na <135 meq/L) or normonatremic on discharge. Three hundred six patients with normal admission Na had either hyponatremia (n= 86) or normal Na (n= 220) on discharge. Compared with patients with normal Na on discharge, hyponatremic patients were younger (p= 0.004), with lower discharge systolic (p <0.001) and diastolic (p= 0.004) blood pressure, higher discharge blood urea nitrogen (p= 0.011) despite similar creatinine (p= 0.566), lower ejection fraction (p= 0.007), and higher left ventricular end-diastolic (p= 0.028) and end-systolic (p= 0.007) dimensions. Despite comparable congestion on hospital admission, patients with discharge hyponatremia had a higher degree of decongestion throughout hospitalization evident in the significantly greater admission to discharge weight loss (p=0.044) and admission to discharge reduction in inferior vena cava diameter (p=0.014). Despite longer initial hospitalization (p= 0.004), total duration in hospital at 30 days (p= 0.004) and 6 months (p= 0.045), there were no significant differences between patients with discharge hyponatremia versus normal Na on discharge regarding rehospitalization (p= 0.386), all-cause mortality (p= 0.440), and composite of death, cardiac rehospitalization, and cardiac transplant (p= 0.799), all up to 6-month following randomization. Restricted cubic spline analysis also showed no significant relationships between discharge Na and the aforementioned 3 outcomes. Cox proportional hazards regressions showed that discharge hyponatremia did not significantly predict any of the 3 outcomes after adjustment for imbalances at baseline. Among patients with discharge hyponatremia, a poor outcome was more likely if they were also hyponatremic on admission: the composite end point occurred in 69.2% of those also hyponatremic on admission versus 51.2% of those with normal Na on admission but decreased Na on discharge (p= 0.045). Because the median discharge Na level in the discharge hyponatremia group was 132 meq/L, our findings suggest a benign nature of mild discharge hyponatremia in HF patients with normal admission Na.

Protocolo diagnóstico de las alteraciones hidroelectrolíticas en el paciente pluripatológico

Nowadays we usually face pluripathological patients, with chronic treatments. These patients show many electrolyte disorders, which can depend on their chronic disease and their treatments, anintercurrent acute condition or both. Patients with chronic renal failure are the prototype of pluripathological patient with electrolyte disorders, because it can not only cause a large number of disorders itself but also it is usually associated with other diseases. However other frequent pathologies can also present ionic disorders such as hyponatremia in heart failure or hypokalemia in patients suffering arterial hypertension and treated with furosemide or thiazides. Other pathologies can also be diagnosed because of their ionic disorder, as it happens in diabetic patients, where we find metabolic acidosis in relation to hyperglycemic conditions. Poisoning by certain substances, for example metformin or lithium, can also cause ionic disorders.

Prognostic Significance of Hyponatremia Among Ambulatory Patients With Heart Failure and Preserved and Reduced Ejection Fractions

Hyponatremia in heart failure (HF) is an established predictor of adverse outcomes in hospitalized patients with reduced ejection fraction (EF). However, there is a paucity of data in ambulatory patients with HF with preserved ejection fraction (HFpEF). We examined the prevalence, risk factors, and long-term outcomes of hyponatremia (serum sodium ≤135 mEq/L) in ambulatory HFpEF and HF with reduced EF (HFrEF) in a national cohort of 8,862 veterans treated in Veterans Affairs clinics. Multivariable logistic regression models were used to identify factors associated with hyponatremia, and multivariable Cox proportional hazard models were used for analysis of outcomes. The cohort consisted of 6,185 patients with HFrEF and 2,704 patients with HFpEF with a 2-year follow-up. Hyponatremia was present in 13.8% and 12.9% patients in HFrEF and HFpEF, respectively. Hyponatremia was independently associated with younger age, diabetes, lower systolic blood pressure, anemia, body mass index <30 kg/m(2), and spironolactone use, whereas African-American race and statins were inversely associated. In multivariate analysis, hyponatremia remained a significant predictor of all-cause mortality in both HFrEF (hazards ratio [HR] 1.26, 95% confidence interval [CI] 1.11 to 1.44, p <0.001) and HFpEF (HR 1.40, 95% CI 1.12 to 1.75, p = 0.004) and a significant predictor of all-cause hospitalization in patients with HFrEF (HR 1.18, 95% CI 1.07 to 1.31, p = 0.001) but not in HFpEF (HR 1.08, 95% CI 0.92 to 1.27, p = 0.33). In conclusion, hyponatremia is prevalent at a similar frequency of over 10% in ambulatory patients with HFpEF and HFrEF. Hyponatremia is an independent prognostic marker of mortality across the spectrum of patients with HFpEF and HFrEF. In contrast, it is an independent predictor for hospitalization in patients with HFrEF but not in patients with HFpEF.

Unpredictable Nature of Tolvaptan in Treatment of Hypervolemic Hyponatremia: Case Review on Role of Vaptans

Hyponatremia is one of the most commonly encountered electrolyte abnormalities occurring in up to 22% of hospitalized patients. Hyponatremia usually reflects excess water retention relative to sodium rather than sodium deficiency. Volume status and serum osmolality are essential to determine etiology. Treatment depends on several factors, including the cause, overall volume status of the patient, severity of hyponatremic symptoms, and duration of hyponatremia at presentation. Vasopressin antagonists like tolvaptan seem promising for the treatment of euvolemic and hypervolemic hyponatremia in heart failure. Low sodium concentrations cause cerebral edema, but the overly rapid sodium correction can also lead to iatrogenic cerebral osmotic demyelination syndrome. Demyelination may occur days after sodium correction or initial neurologic recovery from hyponatremia. The following case report analyzes the role of vasopressin antagonists in the treatment of hyponatremia and the need for daily dosing of tolvaptan and the monitoring of serum sodium levels to avoid rapid overcorrection which can result in osmotic demyelination syndrome (ODS).

Urine Sodium Excretion by Tolvaptan is Dependent upon Baseline Serum Sodium-Explanation for Improvement of Hyponatremia with less Hypernatremia

We recently defined responders by increased urine volume (UV) during the first day after tolvaptan (TLV) administration. Previous studies have demonstrated that TLV can improve hyponatremia in heart failure (HF) patients. However, changes of serum sodium concentration in responders/non-responders or patients with/without hyponatremia during TLV treatment have not been analyzed.