Optimal Patient Selection and Treatment Timing for Tolvaptan Therapy Following Cardiovascular Surgery

To the Editor:

Matsuda et al demonstrated that post-surgical low-dose tolvaptan therapy did not shorten the time to achieving preoperative body weight compared with conventional diuretic therapy.¹

Optimal patient selection is key to successful tolvaptan therapy. In general, tolvaptan is indicated for patients refractory to conventional diuretics.² Patients should be sufficiently sick to enjoy the benefit of tolvaptan. In the study of Matsuda et al, most patients had preserved renal function and the response to loop diuretics in the control group was acceptable.¹ Patients with left ventricular ejection fraction <40% and those with a glomerular filtration ratio <30 mL/min/1.73 m² were excluded from the study. These patients may be rather good candidates for tolvaptan therapy.

However, not all patients are good candidates for tolvaptan therapy. For example, our team proposed a novel index to identify responders to tolvaptan, namely the ratio of urine aquaporin-2 relative to plasma arginine vasopressin, which represents the residual function of the renal collecting duct.³ It may be of great interest to investigate other predictors that are associated with the achievement of the primary endpoint in the study of Matsuda et al.

The optimal timing to initiate tolvaptan is another concern. Matsuda et al initiated tolvaptan on postoperative Day 2. Earlier initiation of tolvaptan orally or intravenously may have more clinical benefit by increasing urine volume and maintaining renal function.⁴

Disclosures

None.

• Kotaro Horie
• Teruhiko Imamura, MD, PhD
• Second Department of Internal Medicine, University of Toyama, Toyama, Japan

References

• 1.   Matsuda Y, Koyama T, Yoshida K, Koizumi S, Nakamura K, Ishigami M, et al. Effects of low-dose tolvaptan for fluid management after cardiovascular surgery. Circ Rep 2022; 4: 563–570.
• 2.   Imamura T, Kinugawa K. Update of acute and long-term tolvaptan therapy. J Cardiol 2019; 73: 102–107.
• 3.   Imamura T, Kinugawa K, Fujino T, Inaba T, Maki H, Hatano M, et al. Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure. Circ J 2014; 78: 2240–2249.
• 4.   Yokoyama S, Imamura T, Yamashita S, Doi T, Fukahara K, Yoshimura N, et al. Peak lag between plasma vasopressin and urine aquaporin-2 following cardiac surgery. Int Heart J 2021; 62: 1057–1061.