Right ventricular enlargement predicts responsiveness to tolvaptan in congestive heart failure patients with reduced ejection fraction

Abstract

BackgroundTolvaptan is a vasopressin type 2 receptor antagonist used in heart failure (HF) with refractory diuretic resistance. However, since tolvaptan is also ineffective in some HF patients with reduced ejection fraction (HFrEF), the identification of responders is important.MethodsThe study population consisted of 51 HFrEF patients who were administered tolvaptan (EF, 28 ± 7%). We defined responders as patients with a ≥50% increase in urine volume during the 24-hours after administration of tolvaptan. All patients underwent comprehensive transthoracic echocardiography before administration of tolvaptan. Patients were followed for 120 days to ascertain secondary events (cardiac death and rehospitalization for HF).ResultsMultiple regression analysis indicated that right ventricular (RV) enlargement (defined as basal RV diameter > 41 mm and midlevel RV diameter > 35 mm, according to guidelines) remained a predictor of response after adjustment for age, sex, starting dosage of tolvaptan, and estimated glomerular filtration rate (odds ratio, 4.88; 95%-confidence interval, 1.26–18.9; P < 0.05), whereas left ventricular parameters and RV dysfunction were not. Kaplan-Meier curves indicated responsiveness to tolvaptan was associated with better prognosis among the overall population (P < 0.05); similar trends were observed among patients with RV dilatation (P = 0.056).ConclusionsThese findings suggest that RV enlargement, which represents right-sided volume overload, elevated filling pressure, and diastolic dysfunction similar to that seen in constrictive pericarditis, predicts responsiveness to tolvaptan in patients with HFrEF. Moreover, administration of tolvaptan may have the potential to improve the reportedly poor prognosis for HFrEF patients with RV dilatation.

Prognostic Relevance of Right Ventricular Remodeling after ST-Segment Elevation Myocardial Infarction in Patients Treated With Primary Percutaneous Coronary Intervention

“…This may not only alleviate symptoms but also positively affect cardiac output and systemic organ perfusion. A pilot study by Nonin et al 23 in patients with HFrEF showed a greater response to a selective vasopressin type 2 receptor antagonist in terms of 24hour urine output in patients who had undergone adverse RV remodeling. In addition, selective vasopressin type 2 receptor antagonist responders experienced a better prognosis.…”

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

“…Our study confirms that tolvaptan can augment diuresis and increase sodium levels in LVAD patients during the postoperative period. Vasopressin antagonists may have particular a benefit in patients with right ventricular dysfunction 10 . This is highly relevant for the LVAD population where right ventricular dysfunction is prevalent due to the chronic, advanced nature of heart failure in these patients.…”

“…Furthermore, patients with right ventricular dilation, suggesting elevated right‐sided filling pressures and right ventricular failure, have been shown to be associated with tolvaptan responsiveness. One subset of patients that may derive particular benefit from tolvaptan is those with right ventricular failure, due to the frequent association of right ventricular failure with hyponatremia, diuretic resistance, and improved clinical response to tolvaptan 7–10 …”

“…One subset of patients that may derive particular benefit from tolvaptan is those with right ventricular failure, due to the frequent association of right ventricular failure with hyponatremia, diuretic resistance, and improved clinical response to tolvaptan. [7][8][9][10] Left ventricular assist device (LVAD) implantation is becoming increasingly common for patients with advanced heart failure. 11 Right ventricular failure is a frequent occurrence following LVAD implantation, particularly in the early postoperative period, and requires aggressive volume management to maintain appropriate preload.…”

Predictors of Tolvaptan Response as a Therapy Optimization Strategy in Heart Failure Patients: A Narrative Review

“…Studi ini juga mengidentifikasi bahwa responder tolvaptan memiliki prognosis yang lebih baik terhadap laju kematian-kardiak dan rehospitalisasi GJ dalam 120 hari. 39 Kogure et al, 2018: Sebanyak 92 pasien congestive heart failure (CHF) dianalisis secara retrospektif. Pasien dikatakan sebagai responder ketika nilai puncak keseimbangan cairan mencapai >500 mL dalam 4 hari setelah tolvaptan diberikan.…”