← Back to October 2017

Right Ventricular Dysfunction After Left Ventricular Assist Device Placement and Cardiac Transplantation - Take a Deep Breath

David Salerno, PharmD

Douglas L. Jennings, PharmD, FAHA, FACC

New York Presbyterian Hospital
New York, NY, USA

Right ventricular failure (RVF) after heart transplant (HT) or implantation of a continuous-flow left ventricular assist device (CF-LVAD) is associated with significant post-operative morbidity and mortality [1,2]. Estimates of RVF after CF-LVAD implantation and HF have been as high as 45% [3,4]. In addition to non-pharmacological modalities and intravenous vasodilators, inhaled pulmonary vasodilators are a unique treatment option aimed at minimizing systemic absorption by delivering therapy directly to the pulmonary vasculature. No formal guidelines endorse agent selection, dosing or administration of inhaled pulmonary vasodilators post-LVAD or HT.

Even small increases in RV afterload secondary to rising pulmonary pressures can contribute to RVF [5,6]. RV function may worsen early after CF-LVAD implantation secondary to excessive unloading of the LV by the device. After HT, ischemia and reperfusion injury associated with organ preservation, cold ischemia time as well as elevated pulmonary pressures contribute to a weaker RVF [4,7,8].

Inhaled pulmonary vasodilators are primarily administered via endotracheal tube during mechanical ventilation. Inhaled administration presents several challenges: variability introduced by administration setup, nebulizer type utilized for aerosolization, mechanical ventilator mode and dosage form. Below are a summary of the agents available:


Mechanism of Action

Common Doses


Inhaled nitric oxide

Activates intracellular guanylyl cyclase, which increases concentrations of cyclic guanosine 3'5'-monophosphate

1 to 20 parts per million via continuous inhalation

  • Very short half-life
  • Can cause methemoglobinemia
  • Expensive
  • Limited systemic exposure

Inhaled epoprostenol

Activates intracellular adenylate cyclase, which increases concentrations of cyclic adenosine monophosphate

25 to 50 nanograms/kg/min OR Fixed volume of 8 mL/hour

  • Complicated administration
  • Patient must be intubated
  • Less expensive
  • Some systemic exposure
    • Potential for platelet inhibition and bleeding
    • Potential hypotension

Inhaled iloprost

Activates intracellular adenylate cyclase, which increases concentrations of cyclic adenosine monophosphate

5 to 10 mcg inhaled 6 to 9 times daily

  • Ease of administration
  • Patient can be extubated
  • Expensive
  • Some systemic exposure
    • Potential for platelet inhibition and bleeding
    • Potential hypotension

Inhaled milrinone

Inhibits phosphodiesterase III, which increases concentrations of cyclic adenosine monophosphate

6 mg/hour continuous inhalation

  • Less evidence of clinical efficacy
  • Patient must be intubated
  • Less expensive
  • Systemic exposure
    • Potential hypotension
    • Arrhythmia

Dosing and administering inhaled pulmonary vasodilators can be cumbersome due to complicated dosing regimens or drug compatibility issues. For instance, a weight-based epoprostenol dosing strategy requires a dual infusion setup of reconstituted drug and normal saline due to lack of compatibility with epoprostenol. For this approach, one bottle of reconstituted epoprostenol (30,000 ng/mL) is infused through an IV pump, and a 500 mL bag of 0.9% normal saline is infused through a second, separate IV pump. The infusion rate of reconstituted epoprostenol is calculated based on the desired dose (10-50 ng/kg/min based on ideal body weight), and infusion rate of saline is added to attain a combined total infusion rate of 8 mL/h (the aerosol output of the nebulizer).

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 HT (see table below). However, the literature regarding the potential impact on clinical outcomes (e.g., survival or risk of developing RVF) is lacking with these medications.





Rajek et al. 2000(Randomized)

  • Intravenous PGE1
  • Inhaled NO
  • HT (n=34)
  • Immediately after weaning PVR decreased by 50% in NO group vs. 10% in IV PGE1 group
  • At 6 hours mPAP and PVR were similar between groups
  • Weaning from CPB failed in no patients in NO group vs. 6 patients in IV PGE1 group

Ardehali et al. 2001 (retrospective)

  • Inhaled NO, withdrawal for 15 minutes
  • Historical control
  • HT (n=16)
  • Discontinuation of NO for 15 minutes at 6 hours resulted in significant increase in mPAP, PVR, and RVSWI

Macdonald et al. 1998

  • Inhaled NO, with withdrawal at 24 hours
  • CF-LVAD (n=7)
  • Withdrawal at 24 hours associated with rise in transpulmonary gradient and PVR

Khan et al. 2009

  • Inhaled NO
  • Inhaled epoprostenol
  • HT and lung transplant recipients (n=25)
  • Both agents reduced mPAP, CVP, and improved mixed venous oxygen saturations
  • At 6-hr crossover, no differences in pulmonary pressures or systemic blood pressure

Theodoraki et al. 2006

  • Inhaled iloprost
  • HT (n=8)
  • Iloprost decreased transpulmonary gradient, mPAP, and PVR

Haglund et al. 2015

  • Inhaled milrinone
  • CF-LVAD (n=10)
  • mPAP decreased and cardiac index and right atrial pressures improved
  • No atrial arrhythmias or sustained hypotension observed

After review of the literature, we suggest that when RVF failure occurs in the setting of a normal pulmonary vascular resistance (PVR), first line therapy should be traditional intravenous inotropic therapy. However, if the PVR is elevated (> 250 dynes/sec/cm5 or 3 Wood units), or the patient has other evidence of a high RV afterload (i.e., a transpulmonary gradient > 12 mm Hg), then an inhaled pulmonary vasodilator is 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. ■

Disclosure Statement: The authors have no conflicts of interest to disclose.


  1. Writing Group M, Mozzaffarian D, Benjamin EJ, et al. Heart disease and stroke statistics-2016 update: a report from the American heart association. Circulation. 2016; 133; e38-360.
  2. Sabato LA, Salerno DM, Moretz JD, et al. Inhaled pulmonary vasodilator therapy for management of right-ventricular dysfunction after left ventricular assist device placement and cardiac transplantation. Pharamcotherapy. 2017; [Epub ahead of print].
  3. Lampert BC, Teuteberg JJ. Right ventricular failure after left ventricular assist devices. J Heart Lung Transplant 2015;34:1123-30.
  4. Kobashigawa J, Zuckermann A, Macdonald P, et al. Report from a consensus conference on primary graft dysfunction after cardiac transplantation. J Heart Lung Transplant 2014;33:327-40.
  5. Voelkel NF, Quaife RA, Leinwand LA, et al. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation. 2006;114:1883-91.
  6. Vonk-Noordegraaf A, Haddad F, Chin KM, et al. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol. 2013;62:D22-33.
  7. Stobierska-Dzierzek B, Awad H, Michler RE. The evolving management of acute right-sided heart failure in cardiac transplant recipients. J Am Coll Cardiol 2001;38:923-31.
  8. Chang PP, Longenecker JC, Wang NY, et al. Mild vs severe pulmonary hypertension before heart transplantation: different effects on posttransplantation pulmonary hypertension and mortality. J Heart Lung Transplant 2005;24:998-1007.

Share via:

links image    links image    links image    links image