Postoperative tolvaptan use in left ventricular assist device patients: The TOLVAD randomized pilot study

Abstract

Purpose Tolvaptan, a selective vasopressin type‐2 antagonist, has been shown to increase serum sodium (Na) and urine output in hyponatremic left ventricular assist device (LVAD) patients in retrospective studies. In this prospective randomized pilot study, we aimed to assess the efficacy of tolvaptan in this population. Methods We conducted a prospective, randomized, non‐blinded pilot study of LVAD recipients with post‐operative hyponatremia (Na < 135 mEq/L) (NCT05408104). Eligible participants were randomized to receive tolvaptan 15 mg daily in addition to usual care versus usual care alone. The primary outcome was a change in Na level and estimated glomerular filtration rate (eGFR), from the first post‐operative day of hyponatremia (the day of randomization) to discharge. Results A total of 33 participants were enrolled, and 28 underwent randomization (median age 55 [IQR 50–62]), 21% women, 54% Black, 32% ischemic cardiomyopathy, median baseline Na 135 (IQR 134–138). Fifteen participants were randomized to tolvaptan (TLV) and 13 were randomized to usual care alone (No‐TLV). Mean change in Na from randomization to discharge in the TLV group was 2.7 mEq/L (95%CI 0.7–4.7, p = 0.013) and 1.8 (95%CI 0.5–4.0, p = 0.11) in the No‐TLV group, though baseline and final Na levels were similar between groups. The mean change in eGFR was 2.6 ml/min/1.73 m2 (95%CI 10.1–15.3, p = 0.59) in TLV versus 7.5 ml/min/1.73 m2 (95%CI 5.2–20.2, p = 0.15) in No‐TLV. TLV participants had significantly more urine output than No‐TLV patients during their first 24 h after randomization (3294 vs 2155 ml, p = 0.043). Conclusion TLV significantly increases urine output, with nominal improvement in Na level, in hyponatremic post‐operative LVAD patients without adversely impacting renal function.

The treatment with trandolapril and losartan attenuates pressure and volume overload alternations of cardiac connexin-43 and extracellular matrix in Ren-2 transgenic rats

“…Currently, the treatment of HF is based on a combination of drugs aimed at suppressing activation of the sympathetic nervous system, the RAS and agents that positively influence sodium and glucose metabolism 22 . Undoubtedly, the better understanding of yet unravelled mechanisms and processes may promote novel and more effective therapies to improve outcomes 23 .…”

Impact of volume overload on cardiac connexin-43 and extracellular matrix of normotensive and hypertensive Ren-2 transgenic rats: Effects of treatment with Trandolapril and Losartan

“…Currently, the treatment of HF is based on a combination of drugs aimed at suppressing activation of the sympathetic nervous system, the RAS and agents that positively in uence sodium and glucose metabolism 22 . Undoubtedly, the better understanding of yet unravelled mechanisms and processes may promote novel and more effective therapies to improve outcomes 23 .…”