Bosentan in heart transplantation candidates with severe pulmonary hypertension: efficacy, safety and outcome after transplantation

Pérez‐Villa, Félix; Farrero, Marta; Cardona, M.; Castel, María Ángeles; Tatjer, I.; Penela, Diego; Vallejos, I.

doi:10.1111/j.1399-0012.2012.01689.x

Cited by 17 publications

(20 citation statements)

References 21 publications

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“…This is in agreement with previous reports on the beneficial effect of bosentan therapy on PVR and diastolic pulmonary pressure, which enabled a subset of responders to bosentan to become eligible for heart transplantation [7, 11]. After bosentan titration, PVR decreased by 60% compared with baseline values at the 12-month follow-up in heart transplant candidates with severe PH [12]. The reduction in PVR with bosentan therapy is associated with favorable outcome after transplantation and LV assist device implantation [12, 13].…”

Section: Discussionsupporting

confidence: 91%

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Effect of Bosentan on Pulmonary Hypertension Secondary to Systolic Heart Failure

Padeletti¹,

Caputo²,

Zacà³

et al. 2013

Pharmacology

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Objectives: The dual endothelin receptor antagonist bosentan improves pulmonary vascular resistance (PVR) in patients with primary pulmonary hypertension (PH). The effects of bosentan on secondary PH due to systolic heart failure (HF) are not well defined. This study evaluates the effect and tolerability of bosentan in patients with PH secondary to HF. Methods: Seventeen adult HF patients with PH and New York Heart Association class III-IV symptoms were treated with bosentan, 62.5 mg twice daily, for 1 month, which was gradually increased to 125 mg twice daily thereafter. Right heart catheterization (RHC), a clinical evaluation and echocardiographic measurements were performed at baseline and at 4 ± 3 (mean ± SD) months of follow-up. Response to bosentan was defined as an improvement in clinical, echocardiographic and RHC parameters. Results: Six patients did not complete the study (therapy was discontinued due to hypotension, elevated liver enzymes or acute decompensation of HF), 11 patients completed the follow-up; 9 patients responded to therapy. Systemic arterial pressures, pulmonary pressures, PVR and the transpulmonary gradient significantly decreased compared with baseline levels in 9 responders (p = 0.05, 0.05, 0.01 and 0.004, respectively), and 4 became eligible for heart transplantation and 3 for left ventricular assist device implantation. Conclusions: Bosentan decreased pulmonary pressures and PVR in the majority of patients with PH secondary to systolic HF, thereby allowing them to be considered candidates for heart transplantation.

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Section: Discussionsupporting

confidence: 91%

“…After bosentan titration, PVR decreased by 60% compared with baseline values at the 12-month follow-up in heart transplant candidates with severe PH [12]. The reduction in PVR with bosentan therapy is associated with favorable outcome after transplantation and LV assist device implantation [12, 13]. …”

Section: Discussionmentioning

confidence: 99%

Effect of Bosentan on Pulmonary Hypertension Secondary to Systolic Heart Failure

Padeletti¹,

Caputo²,

Zacà³

et al. 2013

Pharmacology

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“…Though modest in extent, the clinical behavior post‐OHT was dramatic and more akin to pre‐capillary PH physiology characterized by PH crisis and death. Though small studies in non‐CHD OHT recipients treated with PH‐directed therapy pre‐transplant show promising results with good survival, reversal of PH, and good functional capacity in survivors, larger studies are lacking, especially in CHD. These two patients alone exemplify the need to better understand the nature and treatment of PAH in CHD.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary arterial hypertension in adults with systemic right ventricles referred for cardiac transplantation

Kim

Awh

Acker

et al. 2019

Clinical Transplantation

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Background Systemic right ventricular (RV) failure may progress necessitating referral for orthotropic heart transplantation (OHT). Pulmonary hypertension (PH) frequently coexists in adult congenital heart disease and can complicate the assessment for OHT. Methods Single‐center case series of six patients (median age 34.9 years [IQR, 31.9‐42.4]) with systemic RV physiology with PH referred for OHT evaluation from 2008 to 2017. Results One‐third (n = 6) of 18 patients with systemic RV physiology referred for OHT evaluation had pulmonary arterial hypertension (PAH) defined as mean pulmonary artery pressure (mPAP) > 25 mm Hg and pulmonary vascular resistance (PVR) > 3 Wood Units. Two of the six patients were considered OHT‐ineligible due to PH and comorbidities. Of the remaining four, two had pre‐capillary PH and underwent heart‐lung transplant (HLTx). The other two demonstrated reversibility of PVR with vasodilator testing and underwent OHT alone, one of whom died post‐transplant from PH crisis. Conclusions Pulmonary arterial hypertension is common in systemic RV patients referred for OHT. Systemic RV dysfunction places these patients at risk for post‐capillary PH but pre‐capillary PH can exist. Despite management with selective pulmonary vasodilators and afterload reduction, criteria for listing patients for HLTx vs OHT are not known and need further elucidation.

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“…, Perez‐Villa et al . ). Hefke and colleagues reported that bosentan was an independent predictor of reduced mortality in a group of 84 patients on the waiting list for heart transplantation (Hefke et al .…”

Section: The Treatment Of Ph Due To Lhfmentioning

confidence: 97%

“…reported that 12 months of bosentan therapy reversed previously defined irreversible PVR in 19 of 26 patients, making them eligible for heart transplantation (Perez‐Villa et al . ). They also observed that one‐year survival among the 14 patients who underwent heart transplantation was similar to that in the 56 patients who did not have increased PVR prior to heart transplantation (Perez‐Villa et al .…”

Section: The Treatment Of Ph Due To Lhfmentioning

confidence: 97%

Pathophysiology and potential treatments of pulmonary hypertension due to systolic left heart failure

Lundgren

Rådegran

2014

Acta Physiologica

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Pulmonary hypertension (PH) due to left heart failure is becoming increasingly prevalent and is associated with poor outcome. The precise pathophysiological mechanisms behind PH due to left heart failure are, however, still unclear. In its early course, PH is caused by increased left ventricular filling pressures, without pulmonary vessel abnormalities. Conventional treatment for heart failure may partly reverse such passive PH by optimizing left ventricular function. However, if increased pulmonary pressures persist, endothelial damage, excessive vasoconstriction and structural changes in the pulmonary vasculature may occur. There is, at present, no recommended medical treatment for this active component of PH due to left heart failure. However, as the vascular changes in PH due to left heart failure may be similar to those in pulmonary arterial hypertension (PAH), a selected group of these patients may benefit from PAH treatment targeting the endothelin, nitric oxide or prostacyclin pathways. Such potent pulmonary vasodilators could, however, be detrimental in patients with left heart failure without pulmonary vascular pathology, as selective pulmonary vasodilatation may lead to further congestion in the pulmonary circuit, resulting in pulmonary oedema. The use of PAH therapies is therefore currently not recommended and would require the selection of suitable patients based on the underlying causes of the disease and careful monitoring of their progress. The present review focuses on the following: (i) the pathophysiology behind PH resulting from systolic left heart failure, and (ii) the current evidence for medical treatment of this condition, especially the role of PAH-targeted therapies in systolic left heart failure.

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Bosentan in heart transplantation candidates with severe pulmonary hypertension: efficacy, safety and outcome after transplantation

Abstract: In patients considered high-risk candidates for heart transplantation because of high PVR, therapy with bosentan is associated with a significant reduction in PVR and a good outcome after transplantation.

Cited by 17 publications

References 21 publications

Effect of Bosentan on Pulmonary Hypertension Secondary to Systolic Heart Failure

Effect of Bosentan on Pulmonary Hypertension Secondary to Systolic Heart Failure

Pulmonary arterial hypertension in adults with systemic right ventricles referred for cardiac transplantation

Pathophysiology and potential treatments of pulmonary hypertension due to systolic left heart failure

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