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Vol. 66. Issue 6.
Pages 503-504 (June 2013)
Vol. 66. Issue 6.
Pages 503-504 (June 2013)
Scientific letter
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Efficacy of Tolvaptan in Patients Hospitalized for Heart Failure With Refractory Hyponatremia. Clinical Experience in Daily Practice
Eficacia de tolvaptán en pacientes ingresados por insuficiencia cardiaca e hiponatremia refractaria. Experiencia en la práctica clínica diaria
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Nahikari Salterain-Gonzaleza, Alberto Esteban-Fernándeza,
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athalbertus@gmail.com

Corresponding author:
, Martín García-Lópezb, Francisco J. Lavilla-Royob, Juan J. Gavira-Gómeza
a Unidad de Insuficiencia Cardiaca, Departamento de Cardiología, Clínica Universidad de Navarra, Pamplona, Navarra, Spain
b Departamento de Nefrología, Clínica Universidad de Navarra, Pamplona, Navarra, Spain
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To the Editor,

Hyponatremia (plasma sodium =135 mEq/L) is one of the most common electrolyte abnormalities in patients with acute heart failure (HF) and is considered a marker of poor prognosis.1

The latest European Society of Cardiology, Guidelines for HF included tolvaptan, a vasopressin V2-receptor blocker that inhibits free water reabsorption,2 as a valid treatment for patients with refractory hyponatremia.3

We present our experience with tolvaptan for the treatment of refractory hyponatremia in patients admitted by HF.

A retrospective study was conducted in patients treated with tolvaptan who were admitted for HF between February 2011 and August 2012 with refractory hyponatremia (sodium <135mEq/L despite “classic” treatment, mainly fluid intake restrictions and/or administration of hypertonic saline solution) and persistent symptoms of HF.

Plasma sodium, potassium, and creatinine concentrations, glomerular filtration rate (calculated by the Modification of Diet in Renal Disease equation), weight, and excretion rhythm at the start of tolvaptan therapy were assessed 24h and 48h after tolvaptan was given.

The ESTATA/SE 11.1 software package was used for the statistical analysis.

A total of 30 patients (57% women; mean age, 72±14 years) were included. The most common cause of HF (33% of all patients) was ischemic heart disease; 54% of patients presented ventricular dysfunction (mean ejection fraction, 48%±16%). All were following optimal treatment for HF and all were receiving diuretic therapy at home.

Treatment was started at a daily dose of 15mg of tolvaptan in 90% of patients and 30mg in all others. At the start of treatment, sodium was 129±3mEq/L. Natremia was significantly increased at 24h, an effect that persisted at 48h (129±3mEq/L at baseline; 134±3mEq/L at 24h; 135±3mEq/L at 48h; P<.001) (Fig. 1). No significant changes were observed in potassium concentrations after the drug was administered (4±0.5mEq/L at baseline; 4±0.4mEq/L at 24h; 4.2±0.4mEq/L at 48h; P>.05).

Figure 1.

Course of natremia after tolvaptan therapy in patients with acute heart failure and refractory hyponatremia. aP<.05 (natremia at the start of treatment vs natremia at 24h). bP<.05 (natremia at 24h vs natremia at 48h).

(0.06MB).

After treatment, diuresis was significantly increased at 24h, and the effect was maintained at 48h (80±45mL/h, 138±60mL/h, and 136±64mL/h, respectively; P<.001) (Fig. 2). Likewise, a significant decrease in patient weight was observed at 48h (67.1±17.8kg vs 64.1±15.1kg; P=.01).

Figure 2.

Course of diuresis after tolvaptan therapy in patients with acute heart failure and refractory hyponatremia. *P<.05 (diuresis at the start of treatment vs diuresis at 24h).

(0.06MB).

No statistically significant differences were observed in creatinine (1.3±0.5mg/dL at baseline; 1.4±0.4mg/dL at 24h; 1.6±1.1mg/dL at 48h; P>.05) or Modification of Diet in Renal Disease (54±20, 50±16, and 50±18mL/min/1.73m2, respectively; P>.05).

Patients who presented moderate-to-severe hyponatremia (sodium <130 mEq/L) showed a larger post-treatment increase in natremia and excretion rhythm than those who presented mild hyponatremia. These results were similar in patients with ventricular dysfunction or HF with preserved systolic function.

The only adverse event occurred in a patient with no known renal impairment who experienced acute renal failure while receiving treatment and it resolved without dialysis.

In patients with HF, a significant relationship between natremia and in-hospital mortality was observed, along with an increase in readmissions and long-term morbidity and mortality.1,2

Various mechanisms promote this hyponatremia: increased vasopressin due to low cardiac output and decreased renal blood flow, increased perception of thirst, and the use of diuretics.

In patients admitted to our hospital for HF and refractory hyponatremia, we observed a significant increase in the natremia after tolvaptan therapy. Additionally, patients with lower sodium were those who most benefited from treatment, as shown in other studies.4–6 Our study also observed a significant increase in the excretion rhythm and a decrease in weight without significant decline in kidney function or potassium levels, suggesting, that tolvaptan may be a therapeutic option that can be added to loop diuretics, which already have a hyponatremic effect of their own.

Furthermore, our results show similar effects in patients with or without ventricular dysfunction, an important fact taking into account that the prevalence of hyponatremia is similar in both groups.

Therefore, tolvaptan administration in unselected patients with decompensated HF and symptomatic refractory hyponatremia significantly increases sodium concentrations and excretion rhythm without significantly affecting kidney function.

.

References
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M. Gheorghiade, W.T. Abraham, N.M. Albert, W. Gattis Stough, B.H. Greenberg, C.M. O’Connor, et al.
Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry.
Eur Heart J, 28 (2007), pp. 980-988
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Tolvaptan, hyponatremia, and heart failure.
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ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.
Eur Heart J, 33 (2012), pp. 1787-1847
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Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial.
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Acute hemodynamic effects of tolvaptan, a vasopressin V2 receptor blocker, in patients with symptomatic heart failure and systolic dysfunction: an international, multicenter, randomized, placebo-controlled trial.
J Am Coll Cardiol, 52 (2008), pp. 1540-1545
[6]
J.E. Udelson, M. Bilsker, P.J. Hauptman, R. Sequeira, I. Thomas, T. O’Brien, et al.
A multicenter, randomized, double-blind, placebo-controlled study of tolvaptan monotherapy compared to furosemide and the combination of tolvaptan and furosemide in patients with heart failure and systolic dysfunction.
J Card Fail, 17 (2011), pp. 973-981
Copyright © 2012. Sociedad Española de Cardiología
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