Inhaled Pulmonary Vasodilator Therapy for Management of Right Ventricular Dysfunction after Left Ventricular Assist Device Placement and Cardiac Transplantation

Abstract

Right ventricular failure (RVF) after cardiac transplant (CTX) or implantation of a continuous-flow left ventricular assist device (CF-LVAD) is associated with significant postoperative morbidity and mortality. A variety of modalities have been used to treat postoperative RVF, including management of volume status, intravenous inotropes and vasodilators, and right-sided mechanical support. Inhaled vasodilator agents are a unique treatment option aimed at minimizing systemic absorption by delivering therapy directly to the pulmonary vasculature. Current LVAD and CTX guidelines endorse inhaled vasodilators for managing postoperative RVF; however, no guidance is offered regarding agent selection, dosing, or administration. A review of the current literature confirms that inhaled pulmonary vasodilator agents have been shown to decrease pulmonary artery pressure when used in the perioperative period of CF-LVAD implant or CTX. However, the literature regarding the potential impact on clinical outcomes (e.g., survival or risk of developing RVF) is lacking with these medications. Based on our assessment of the literature, we suggest that when RVF occurs in the setting of a normal pulmonary vascular resistance (PVR), traditional inotropic therapy (e.g., dobutamine) should be used. Conversely, if the PVR is elevated (> 250 dynes/sec/cm 5 or 3 Wood units), or the patient has other evidence of a high right ventricular afterload (i.e., a transpulmonary gradient > 12 mm Hg), then an inhaled pulmonary vasodilator would be the preferred initial pharmacologic agent. Drug selection depends largely on the institution's capacity to safely prepare and administer the medication, along with formulary considerations, such as the high costs associated with inhaled iloprost and inhaled nitric oxide. KEY WORDS heart transplantation, left ventricular assist device, right heart failure, pulmonary arterial hypertension, inhaled pulmonary vasodilators. (Pharmacotherapy 2017;37(8):944-955)

Inhaled Pulmonary Vasodilators and Thoracic Organ Transplantation: Does Evidence Support Its Use and Cost Benefit?

“…[4][5][6] PGD in heart transplantation is characterized by left, right, or biventricular dysfunction within 24 hours after transplant surgery and has no identifiable secondary cause. [7][8][9] In thoracic organ transplantation, PGD or its severe form, primary graft failure (PGF), has been reported to affect perioperative morbidity and mortality and thus its pathogenesis has been investigated for possible treatment options. 4,5,7,8 Pulmonary arterial hypertension (PAH) has been reported to be associated with PGD in both heart and lung transplantation.…”

“…[7][8][9] In thoracic organ transplantation, PGD or its severe form, primary graft failure (PGF), has been reported to affect perioperative morbidity and mortality and thus its pathogenesis has been investigated for possible treatment options. 4,5,7,8 Pulmonary arterial hypertension (PAH) has been reported to be associated with PGD in both heart and lung transplantation. [5][6][7]9,10 In general, PAH can easily depress right ventricular (RV) function because the right ventricle ejects blood to the pulmonary circulation, which is normally a less pressurized circuit than systemic circulation.…”

“…[12][13][14] Thus, a key intervention to break this vicious cycle and prevent or treat PGD is to decrease RV afterload by decreasing pulmonary vascular resistance (PVR) while optimizing RV performance. 7,8,10,11,14 Pulmonary vasodilators have been investigated and used clinically to address these issues, with inhaled delivery preferred over intravenous delivery because of fewer systemic side effects, such as coagulopathy or hypotension that lead to decreased coronary perfusion and LV contraction. 2,7,8,[11][12][13][14][15][16][17] Animal studies postulate that inhaled nitric oxide (iNO), one of the inhaled pulmonary vasodilators, might be useful for attenuating ischemia-reperfusion injury-related organ damage at the molecular level.…”

“…7,8,10,11,14 Pulmonary vasodilators have been investigated and used clinically to address these issues, with inhaled delivery preferred over intravenous delivery because of fewer systemic side effects, such as coagulopathy or hypotension that lead to decreased coronary perfusion and LV contraction. 2,7,8,[11][12][13][14][15][16][17] Animal studies postulate that inhaled nitric oxide (iNO), one of the inhaled pulmonary vasodilators, might be useful for attenuating ischemia-reperfusion injury-related organ damage at the molecular level. 7,[17][18][19][20] However, there has been no consensus for medication selection, timing, or dosing, and evidence is lacking on clinical outcomes.…”

“…7,[17][18][19][20] However, there has been no consensus for medication selection, timing, or dosing, and evidence is lacking on clinical outcomes. 7,8 This review summarizes the characteristics of pulmonary vasodilators and assesses evidence of iNO in thoracic organ transplantation in comparison with other pulmonary vasodilators, particularly in relation to their costs because of increased economic pressures on pharmacy and health care delivery.…”