Short-term effects of low-dose tolvaptan on hemodynamic parameters in patients with chronic heart failure

Watanabe, Kiyotaka; Dohi, Kaoru; Sugimoto, Tadafumi; Yamada, Tomomi; Sato, Yuichi; Ichikawa, Kazuhide; Sugiura, Emiyo; Kumagai, Naoto; Nakamori, Shiro; Nakajima, Hiroshi; Hoshino, Kozo; Makino, Hírofumi; Okamoto, Shinya; Onishi, Katsuya; Nakamura, Mashio; Nobori, Tsutomu; M, Ito

doi:10.1016/j.jjcc.2012.09.002

Cited by 53 publications

(44 citation statements)

References 25 publications

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“…Our calculation, therefore, might not be accurate in terms of absolute values, although the trend of sodium excretion should still be valid. 5. We did not demonstrate direct involvement of ENaC or data on aldosterone concentration in the present study, although several previous reports demonstrated a signifi cant relationship between TLV and ENaC in sodium excretion in urine.…”

Section: Discussioncontrasting

confidence: 90%

“…[3][4][5][6][7] We also reported the effi cacy and safety of TLV in (1) amelioration of congestion even in stage D HF patients and (2) improvement of renal function by converting ongoing diuretics to TLV. 8,9) With respect to serum sodium concentration (S-Na), various studies in Europe and the United States have demonstrated the effi cacy of TLV to improve hyponatremia with little chance of hypernatremia, ie, S-Na > 145 mEq/L (eg, 1.7% of hypernatremia in the EVEREST study and 0% in the QUEST study).…”

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confidence: 83%

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Urine Sodium Excretion After Tolvaptan Administration Is Dependent Upon Baseline Serum Sodium Levels

et al. 2014

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SummarySeveral studies have demonstrated that tolvaptan (TLV) can improve hyponatremia in advanced heart failure (HF) patients with rare chance of hypernatremia. However, changes in serum sodium concentrations (S-Na) in patients with or without hyponatremia during TLV treatment have not been analyzed.Ninety-seven in-hospital patients with decompensated HF who had received TLV at 3.75-15 mg/day for 1 week were enrolled. Among 68 "responders", who had achieved any increases in urine volume (UV) during the fi rst day, urinary sodium excretion during 24 hours (U-NaEx 24 ) increased signifi cantly during one week of TLV treatment along with higher baseline S-Na (P < 0.05 and r = 0.325). Considering a cut-off value (S-Na, 132 mEq/L; AUC, 0.711) for any increases in U-NaEx 24 , we defi ned "hyponatremia" as S-Na < 132 mEq/L. In hyponatremic responders (n = 25), S-Na increased signifi cantly, although 1 week was not suffi cient for normalization (125.8 ± 5.0 versus 128.9 ± 4.3 mEq/L, P < 0.05), along with unchanged U-NaEx 24 (2767 ± 2703 versus 2972 ± 2950 mg/day, NS). In contrast, in normonatremic responders (n = 43), S-Na remained unchanged (136.6 ± 3.1 versus 137.4 ± 2.9 mEq/L, NS) along with increased UNaEx 24 (2201 ± 1644 versus 4198 ± 3550 mg/day, P < 0.05).TLV increased S-Na only in hyponatremic responders by way of pure aquaresis, but increased U-NaEx 24 only in normonatremic responders, which explains the scarcity of hypernatremia. Epithelial Na-channels in the distal nephrons, whose repression by TLV increases urinary sodium excretion, may be attenuated by reduced ATP-supply in worse hemodynamics under hyponatremia. (Int Heart J 2014; 55: 131-137) Key words: Heart failure, Vasopressin, Urine osmolality T he orally active vasopressin antagonists vaptans provide potential effects to treat chronic water-retaining disorders. 1) Among them, the vasopressin type 2 (V2) receptor antagonist tolvaptan (TLV) has been available for patients with heart failure (HF) with symptomatic congestion or hyponatremia.2) TLV has been demonstrated to ameliorate congestion, stabilize hemodynamics, and improve renal function without any signifi cant adverse effects.3-7) We also reported the effi cacy and safety of TLV in (1) amelioration of congestion even in stage D HF patients and (2) improvement of renal function by converting ongoing diuretics to TLV. 8,9) With respect to serum sodium concentration (S-Na), various studies in Europe and the United States have demonstrated the effi cacy of TLV to improve hyponatremia with little chance of hypernatremia, ie, S-Na > 145 mEq/L (eg, 1.7% of hypernatremia in the EVEREST study and 0% in the QUEST study). 2,6,[10][11][12] In Japan, we can administer TLV to HF patients to treat their congestion regardless of baseline S-Na as long as hypernatremia or rapid increases in S-Na do not develop. However, no studies have examined the effi cacy and safety of TLV in patients with normonatremia thus far. Therefore, we have analyzed and compared the effect of TLV on S-Na between patients with and witho...

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Section: Discussioncontrasting

confidence: 90%

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confidence: 83%

Urine Sodium Excretion After Tolvaptan Administration Is Dependent Upon Baseline Serum Sodium Levels

et al. 2014

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“…4 One explanation may be that only excretion of free water, and not sodium, is enhanced; particularly in patients with hyponatremia and/or decreased serum osmolality, achieving fluid shift from the interstitial to the intravascular space is difficult. 5,6 The results of long-term treatment with vaptan-class drugs have already been reported in a study using satavaptan, which found no marked improvement in vital prognosis. 7 Those results suggest that blockage of V2 receptors may not lead to improvement of diminished systemic vascular resistance -which is the cause of hyponatremia -and that excessive diuresis may exacerbate the underfilling that underlies cirrhosis.…”

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confidence: 98%

Cirrhosis‐related hyponatremia and the role of tolvaptan

Iwasa¹,

Ishihara

Hasegawa³

et al. 2015

Hepatology Research

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“…[10][11][12][13][14][15][16][17] TLV has a specific feature of excreting only water without increasing electrolyte excretion because it functions as an antagonist to the vasopressin V2 receptor in renal collecting tubules. 18) In addition, it has been shown that TLV treatment resulted in favorable but modest changes in filling pressures (ie, pulmonary capillary wedge pressure, right atrial pressure, and pulmonary artery pressure) associated with a significant increase in urine output.…”

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confidence: 99%

Successful Treatment of Congestive Heart Failure Due to Severe Aortic Valve Stenosis With Low Dose Tolvaptan in Elderly Patients

et al. 2017

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SummaryMedical therapy for severe aortic valve stenosis (AS) is necessary for inoperable patients due to comorbid conditions. Tolvaptan (TLV), unlike other diuretics, resulted in modest changes in filling pressures associated with an increase in urine output, suggesting that TLV improves congestive heart failure (CHF) due to severe AS without hemodynamic instability.We retrospectively investigated 14 consecutive patients ≥ 80 years of age admitted due to decompensated CHF with severe AS at Juntendo University Hospital from April 2014 to November 2015. Seven of the 14 patients were treated with TLV. We examined the safety and efficacy of TLV treatment for severe AS.Mean age was 90.0 ± 6.3 years and mean aortic valve area was 0.57 ± 0.22 cm 2. Urine volume at day 1 of TLV treatment was increased and urine osmolality significantly decreased at day 1 of TLV treatment (all P < 0.05). New York Heart Association classification and brain natriuretic peptide levels significantly improved 1 week after treatment and at discharge (all P < 0.05) whereas brain natriuretic peptide levels did not improve in the patients without TLV. Severe adverse events did not occur during TLV treatment. During the first 3 days, blood pressure and heart rate were relatively stable. TLV treatment did not affect serum creatinine, blood urea nitrogen, or the estimated glomerular filtration rate.In elderly patients with severe AS, TLV treatment improved CHF without hemodynamic instability. Further prospective studies are needed to assess the safety and efficacy of TLV in decompensated heart failure due to severe AS. (Int Heart J 2017; 58: 378-384)

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Short-term effects of low-dose tolvaptan on hemodynamic parameters in patients with chronic heart failure

Abstract: Short-term treatment with low-dose tolvaptan improved hemodynamic parameters and correlated with significant fluid removal in patients with chronic HF.

Cited by 53 publications

References 25 publications

Urine Sodium Excretion After Tolvaptan Administration Is Dependent Upon Baseline Serum Sodium Levels

Urine Sodium Excretion After Tolvaptan Administration Is Dependent Upon Baseline Serum Sodium Levels

Cirrhosis‐related hyponatremia and the role of tolvaptan

Successful Treatment of Congestive Heart Failure Due to Severe Aortic Valve Stenosis With Low Dose Tolvaptan in Elderly Patients

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