Principally, tolvaptan therapy is indicated for patients with heart failure who have reduced renal function and in whom conventional diuretics are ineffective.1 Recently, combination therapy using loop diuretics and tolvaptan has been suggested to decrease volume and stabilize hemodynamics with reduced side effects.2 In addition, it has been reported that after cardiovascular surgery, the usual dose of tolvaptan (7.5 mg/day) decreased postoperative atrial fibrillation (POAF) and worsened renal failure (WRF).3,4 In short, postoperative patients would require appropriate fluid management and prevention of complications (mainly POAF and WRF).
The main aim of our study was to determine whether low-dose tolvaptan (3.75 mg/day) is effective. We selected hemodynamically stable patients who did not undergo dialysis and were at low risk for safety, such as those who had a glomerular filtration rate ≥30 mL/min/1.73 m2 and left ventricular ejection fraction ≥40%.5 The administration of tolvaptan was initiated on postoperative Day (POD) 2; this was because patients are hemodynamically unstable after cardiovascular surgery. However, the earlier initiation of tolvaptan may be clinically beneficial in fluid management, because the low-risk group was hemodynamically stable. Specifically, it may be more effective to initiate tolvaptan on POD1 and to increase the usual dose of tolvaptan in the case of patients who do not respond to low-dose tolvaptan. As a result, although urine volume increased significantly in our study, there was no significant difference in the primary endpoint of achieving preoperative body weight by POD6. In addition, there was no significant difference in the occurrence of complications (POAF and WRF). This may be due to less loop diuretic use in our study, compared with total doses of >100 mg furosemide reported in previous studies.4 We surmise that decreasing the use of loop diuretics and increasing the use of tolvaptan may reduce the occurrence of POAF and WRF.
Moreover, in a subanalysis, we investigated several variables (osmolality, urinary electrolytes, B-type natriuretic peptide) to determine whether they are associated with a response to tolvaptan. Finally, although there were no significant changes in plasma arginine vasopressin concentrations until POD3 in our study, the ratio of urine aquaporin-2 relative to plasma arginine vasopressin may be a predictor of the response to tolvaptan.6
In future, if possible, we would like to conduct a comparative study in a group of patients with poor renal function. However there is a high possibility that this group of patients will be treated with a combination of multiple drugs, such as other diuretics and carperitide, and it will therefore be difficult to evaluate the effects of tolvaptan alone.
Sources of Funding
This study received no funding or grants from any agency or institution.
Disclosures
The authors have no conflicts of interest to disclose.
IRB Information
The trial protocol (n180801) was approved by the Ethics Committee of Kobe City Medical Center General Hospital on August 25, 2018. The study was registered with University Hospital Medical Information Network (UMIN) Clinical Trials Registry (ID: UMIN000033992).
Yasuhiro Matsuda, MD
Department of Cardiovascular Surgery, Kindai University, Osakasayama, Japan
Tadaaki Koyama, PhD
Department of Cardiovascular Surgery, Kobe City Medical Center General Hospital, Kobe, Japan
References
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