Mechanisms of Diuresis for Acute Decompensated Heart Failure by Tolvaptan

Abstract

SummaryTolvaptan, a vasopressin type 2 receptor antagonist, does not affect kidney circulation or cause worsening of renal function (WRF) in patients with acute decompensated heart failure (ADHF). Bioelectrical impedance analysis (BIA) can be used to evaluate intravascular volume by calculating the ratio of extracellular water (ECW) to intracellular water (ICW). There have been no reports examining the mechanisms of tolvaptan-induced diuresis using BIA. We investigated whether tolvaptan decreases excess volume while maintaining intravascular volume in ADHF patients.Study patients included 29 ADHF patients (age 48-95, men 69%) diagnosed between April 2013 and May 2016 and who underwent BIA before and after treatment. Fifteen patients were treated with tolvaptan in addition to conventional diuresis therapy (tolvaptan group), and 14 patients were treated with conventional diuresis therapy only (control group). In the control group, the numerical value of serum creatinine (Cre) significantly increased from 0.89 ± 0.22 mg/ dL to 1.07 ± 0.29 mg/dL (P = 0.004), and the ECW/ICW significantly decreased from 0.696 ± 0.036 to 0.673 ± 0.032 (P = 0.004). These values were not significantly different from those obtained for the tolvaptan group. Furthermore, regression analysis showed a negative correlation between ΔCre and ΔECW/ICW, which are the differences between values before and after treatment (ΔCre = -0.002-5.668 × ΔECW/ICW, r 2 = 0.306, P = 0.002). Our findings suggest that WRF is caused by a reduction in intravascular volume and that tolvaptan treatment can decrease the excess volume while maintaining intravascular volume. (Int Heart J 2017; 58: 593-600)

Combined Evaluation of the Plasma Arginine Vasopressin and Noradrenaline Levels May be a Useful Predictor of the Prognosis of Patients with Acute Decompensated Heart Failure

“…24) It is noteworthy that tolvaptan, a vasopressin V2 receptor antagonist that suppresses the effect of AVP, has been reported to improve symptoms in patients with HF in the short-term. [25][26][27][28] This may be evidence supporting our results that the prognosis of patients with higher plasma AVP levels is poorer and that the suppression of AVP activity may lead to the improvement of the pathophysiological condition in patients with ADHF. More detailed analysis of the physiological activities of AVP and the pathogenesis of HF may expand the spectrum of available treatment options for ADHF.…”

Clinical implications with tolvaptan on monitored bioimpedance-defined fluid status in patients with cirrhotic ascites: an observational study

“…With BIA, Nagayama et al demonstrated different effects on fluid distribution between tolvaptan and furosemide in a patient with liver cirrhosis and chronic kidney disease [38]. Nomoto et al showed that in patients with acute decompensated heart failure, diuresis due to tolvaptan caused no significant change of ECW/ICW ratio by using BIA, while that due to conventional diuretics decreased ECW/ICW ratio [11]. This finding suggested a net reduction of ICW might characterize tolvaptan from conventional diuretics.…”

“…These factors are also common pathophysiological features of fluid control in hemodialysis patients due to chronic renal failure. Body composition and fluid status monitoring assessed by non-invasive BIA, especially intracellular water (ICW), have been shown to be of prognostic value in acute decompensated heart failure, [11] acute kidney injury under continuous hemodiafiltration, [12] and patients with chronic renal failure under hemodialysis [13,14]. Therefore, BIA has also been shown to be an applicable tool for assessment of ICW, even in patients with possible overhydration or vigorous fluid status changes.…”

<p>New therapies for the treatment of heart failure: a summary of recent accomplishments</p>

“…Increased vasopressin levels and the use of loop diuretics can cause hyponatremia 34. Loop diuretics are commonly used in HF treatment;33,36,37 however, up to 30% of patients are resistant to this type of therapy. Other side effects of loop diuretic therapy include electrolyte imbalance or hypotension 34,37,38…”

“…Urine volume is increased but there is no change in the excretion of electrolytes 33–35,39. Studies show that tolvaptan increases serum sodium levels in patients with hyponatremia34,35,37,39 and has a lower tendency for worsening renal function than standard diuretics 36,38…”