1. Chelsea Henderson, PharmD PGY-1 Pharmacy Practice Resident
A hole-in-one: Mastering acute right-heart failure in patients with a patent foramen ovale (PFO)
Chelsea Henderson, PharmD
PGY-1 Pharmacy Practice Resident
VA Boston Healthcare System

2. disclosures
I have nothing to disclose

3. Objectives
- Identify existing evidence for the off-label use of inhaled prostacyclin analogs and phosphodiesterase inhibitor therapy in patients with acute right-heart failure and a PFO
- Describe appropriate treatment strategies to two real patient cases to manage acute-right heart failure due to a PFO and the associated complications

4. Patient case: “Mr. s” Patient case: “Mr. A”
An 80 y/o male with a history of COPD with frequent exacerbations requiring prednisone and antibiotics and a significant cardiac history admitted due to hypoxia and increased dyspnea
Patient appears fine by frequently desaturates without explanation
77 y/o male with shortness of breath and nausea, suspected to be a heart failure exacerbation (ejection fraction = 35%).
Further workup shows evidence of RV strain, acute femoral deep vein thrombosis (DVT) and progressive and profound hypoxia.

5. Patient case: “Mr. s” Patient case: “Mr. A”
2015 right heart catheterization: hypertrophy and pulmonary hypertension, suspected to be Group III, possible regurgitation
 Transthoracic echocardiogram (TTE) and agitated saline study (“Bubble study”) yields a diagnosis of PFO, shows right-to-left shunting of blood
Patient goes into mixed cardiogenic-hypovolemic shock, bilateral pulmonary emboli discovered
After shock is stabilized, TTE and agitated saline study (“Bubble study”) shows PFO

6. Patent Foramen Ovale (PFO)
Congenital cardiac lesion found in up to 25% of the adult population undergoing a transthoracic echocardiogram
Many patients remain asymptomatic
PFO can cause shunting of the cardiac blood flow leading to hypoxemia, paradoxical emboli, and cryptogenic stroke
Can be diagnosed with agitated saline contrast (“Bubble Study”) of the right heart
Torbey E, Thompson PD. Patent foramen ovale: thromboembolic structure or incidental finding? Conn Med Feb;75(2):97-105 
Horton SC, Bunch TJ. Patent foramen ovale and stroke. Mayo Clin Proc Jan;79(1):79-88
Homma S, Sacco RL, Di Tullio MR, et al. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Crytogenic Stroke Study

7. Epoprostenol, Treprostinil and Iloprost
Prostacyclin (PGI2) with strong vasodilatory effects throughout the vasculature, approved for pulmonary arterial hypertension(PAH) Group I
De Wet CJ, Affleck DG, Jacobsohn E, Avidan MS, Tymkew H, Hill LL, Zanaboni PB, Moazami N, Smith JR. Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg Apr;127(4):
Mehmood M, Frank TA. Treatment of right heart failure: is there a solution to the problem? European Journal of Cardiology Practice. 14 (33) Dec

8. Epoprostenol, Treprostinil and Iloprost
Off-label uses
Acute vasodilator testing in patients with PAH
Intraoperative pulmonary hypertension during cardiac surgery with cardiopulmonary bypass
Acute respiratory distress syndrome (ARDS)
Acute right-heart failure, refractory hypoxemia due to ventricular dysfunction
De Wet CJ, Affleck DG, Jacobsohn E, Avidan MS, Tymkew H, Hill LL, Zanaboni PB, Moazami N, Smith JR. Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg Apr;127(4):
Mehmood M, Frank TA. Treatment of right heart failure: is there a solution to the problem? European Journal of Cardiology Practice. 14 (33) Dec

9. FDA-approved for PAH Group I for combination therapy
sildenafil
Phosphodiesterase (PDE5) inhibitor that prolong vasodilatory effects of nitric oxide, other vasodilatory agents
FDA-approved for PAH Group I for combination therapy
Added to epoprostenol to improve oxygenation, exercise capacity, delay clinical worsening
Mehmood M, Frank TA. Treatment of right heart failure: is there a solution to the problem? European Journal of Cardiology Practice. 14 (33) Dec
Product Information: REVATIO oral tablets, suspension, intravenous injection, sildenafil oral tablets, suspension, intravenous injection. Pfizer (per manufacturer), New York, NY, 2015.

10. Evidence for PGI2 and PDE5 use in right-heart failure with a PFO
Pitsiou GG, Chavouzis N, Nakou C, et al
40 y/o woman with idiopathic pulmonary arterial hypertension (iPAH), severe dyspnea and hypoxia
TTE: right ventricular hypertrophy with severe enlargement of the right ventricle, right atrium
Agitated saline injections revealed severe right-to-left shunt through a PFO 
Sildenafil 25 mg orally three times daily and inhaled iloprost 20 mcg aerolized six times daily initiated concomitantly  hemodynamic stability five days later
Pitsiou GG, Chavouzis N, Nakou C, et al. Successful up-front combination therapy in a patient with idiopathic pulmonary hypertentions and patent foramen ovale: an alternative to epoprostenol therapy? J Heart Lung Transplant Jun;28(6):651-3

11. Evidence for PGI2 and PDE5 use in right-heart failure with a PFO
Elias S, Sviri S, Orenbush-Harroch E, et al.
67 y/o women with severe pulmonary hypertension, dependent on inhaled nitric oxide and mechanical ventilation (unable to wean)
TEE: severe enlargement of the right ventricle with severe dysfunction, pulmonary hypertension, mitral regurgitation
Agitated saline injections revealed severe right-to-left shunt due to a PFO
Sildenafil 20 mg orally three times daily up to 60 mg three times daily x 5 days allowed full weaning after 25 days of mechanical ventilation and nitric oxide therapy
Elias S, Sviri S, Orenbush-Harroch E, et al. Sildenafil to facilitate weaning from inhaled nitric oxide and mechanical ventilation in a patient with severe secondary pulmonary hypertension and a patent foramen ovale. Respir Care Oct;56(10):1611-3

12. Patient case: “Mr. s”
Patient case: “Mr. A”
Inhaled epoprostenol started at ng/kg/min (IBW)
Weaned down from 50 ng/kg/min by increments of 10 ng/kg/min in intervals of 2 to 4 hours as tolerated
Inhaled epoprostenol started at ng/kg/min (IBW)
Weaned down from 50 ng/kg/min by increments of 10 ng/kg/min in intervals of 2 to 4 hours as tolerated

13. Patient case: “Mr. s”
Patient case: “Mr. A”
Maintained on sildenafil 25 mg three times daily and epoprostenol for three days, then epoprostenol discontinued
Despite his hemodynamic instability, bilateral PE and acute right-heart failure due to PFO, Mr. A fully recovered and is maintained on oral sildenafil 25mg three times daily
Inhaled treprostinil started when epoprostenol dose weaned to 10 ng/kg/min x 2 doses of treprostinil, then epoprostenol discontinued
Patient discharged to home and maintained outpatient on inhaled treprostinil four times daily and oral sildenafil 25 mg three times daily

14. summary
Utilizing off-label inhaled prostacyclin and phosphodiesterase inhibitor therapy in patients with acute right-heart failure and a PFO may improve ventricular function and oxygenation

15. A hole-in-one: Mastering acute right-heart failure in patients with a patent foramen ovale (PFO)
Questions?
Chelsea Henderson, PharmD
PGY-1 Pharmacy Practice Resident
VA Boston Healthcare System

16. Acknowledgements Lauren Finlay, PharmD
Clinical Pharmacy Specialist, VABHS
Bryan Wood, PharmD
PGY-1 Residency Director

17. Assessment question #1
A patent foramen ovale (PFO) may result in which of the following… a. Acute left-heart failure b. Decreased systolic ejection fraction c. Cryptogenic stroke d. Prolonged PT/INR

18. Assessment question #1
A patent foramen ovale (PFO) may result in which of the following… a. Acute left-heart failure b. Decreased systolic ejection fraction c. Cryptogenic stroke d. Prolonged PT/INR

19. Assessment question #2
Which of the following medications has NOT been used for off-label treatment of acute right-heart failure?
Furosemide
Epoprostenol
Sildenafil
Iloprost

20. Assessment question #2
Which of the following medications has NOT been used for off-label treatment of acute right-heart failure?
Furosemide
Epoprostenol
Sildenafil
Iloprost

21. References
Torbey E, Thompson PD. Patent foramen ovale: thromboembolic structure or incidental finding? Conn Med Feb;75(2):97-105 
Horton SC, Bunch TJ. Patent foramen ovale and stroke. Mayo Clin Proc Jan;79(1):79-88
Homma S, Sacco RL, Di Tullio MR, et al. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Crytogenic Stroke Study
De Wet CJ, Affleck DG, Jacobsohn E, Avidan MS, Tymkew H, Hill LL, Zanaboni PB, Moazami N, Smith JR. Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg Apr;127(4):
Mehmood M, Frank TA. Treatment of right heart failure: is there a solution to the problem? European Journal of Cardiology Practice. 14 (33) Dec
Product Information: REVATIO oral tablets, suspension, intravenous injection, sildenafil oral tablets, suspension, intravenous injection. Pfizer (per manufacturer), New York, NY, 2015.
Pitsiou GG, Chavouzis N, Nakou C, et al. Successful up-front combination therapy in a patient with idiopathic pulmonary hypertentions and patent foramen ovale: an alternative to epoprostenol therapy? J Heart Lung Transplant Jun;28(6):651-3
Elias S, Sviri S, Orenbush-Harroch E, et al. Sildenafil to facilitate weaning from inhaled nitric oxide and
mechanical ventilation in a patient with severe secondary pulmonary hypertension and a patent
foramen ovale. Respir Care Oct;56(10):1611-3