1. Pulmonary Hypertension: Management Update
Robert Vassallo, MD
Division of Pulmonary and Critical Care Medicine
Mayo Clinic, Rochester, MN.
KUWAIT 2014

2. Disclosures
I have nothing to disclose with respect to this presentation.

3. Key objectives of this presentation
Review WHO updated classification of pulmonary hypertension.
Review diagnostic approach and caveats with testing for pulmonary hypertension.
Outline a clinical rationale for the management of pulmonary hypertension.
Discuss situations when expert opinion and referral to specialized centers may be necessary.

4. Pulmonary Hypertension
Concept…
…progressive increase in the blood pressure in the pulmonary vascular bed
Consequence…
…right heart failure and death

5. Criteria for Pulmonary Hypertension
Mean Pulmonary Artery Pressure MPAP > 25 mmHg at rest with pulmonary capillary wedge pressure ≤15 mm Hg
4th World Symposium on Pulmonary Hypertension, Dana Point, CA 2008

6. Potential sites to induce Pulmonary Hypertension
Post-capillary
Pre-capillary

7. Updated Clinical Classification of Pulmonary Hypertension
Pulmonary arterial hypertension (PAH)
idiopathic (“primary pulmonary hypertension”)
secondary to systemic disorders
Pulmonary hypertension due to left heart disease (pulmonary venous hypertension)
Pulmonary hypertension associated with respiratory disease and/or hypoxia
COPD, Interstitial lung disease, OSA
Chronic thromboembolic/embolic pulmonary hypertension
Pulmonary hypertension from unclear mechanisms
Journal of the American College of Cardiology
Vol. 62, No. 25, Suppl D, 2013

8. Mean pulmonary artery pressure and cardiac output relationship90 60 30
Severe
Mild to moderate
Mean PA pressure
Normal
REST EXCERCISE
Cardiac Output [L/min]

9. Signs and symptoms of Pulmonary Hypertension
Symptoms and signs are usually not specific; delay in diagnosis very common.
Early – dyspnea with activity.
Late symptoms:
syncope
chest pain / chest pressure
leg edema (signs of right heart failure)
abnormal findings on chest X ray or ECG

10. Diagnostic studies: Chest radiography
Radiographic findings are subtle and often missed

11. ECG abnormalities Right heart strain (RVH and RA enlargement)
Non-specific
Right axis deviation
ST depression and T wave inversion V1-V3

12. Screening for pulmonary hypertension
There is no perfect screening tool.
Transthoracic echocardiography
Goals:
1. determine right ventricular size and systolic function
2. estimate right ventricular systolic pressure

13. Diagnostic testing: Trans-thoracic echocardiography
Echocardiography uses Doppler ultrasound to estimate the pulmonary artery systolic pressure
PASP = (4 x [TRV]2) + RAP LA RA LV RV
Echo transducer CP
DV Revised

14. Pulmonary hypertension diagnosis via right heart catheterization
From Mayo Clinic Right Heart Catheterization Training Manual – Cardiology Rotation

15. Clinical approach to suspect pulmonary hypertension
If the echocardiogram suggests the presence of pulmonary hypertension
1. perform careful evaluation for secondary causes
2. consider whether you should proceed to right heart catheterization

16. Once you have identified pulmonary hypertension, look for causes
Pulmonary arterial hypertension (PAH)
idiopathic (“primary pulmonary hypertension”)
secondary to systemic disorders
Pulmonary hypertension due to left heart disease (pulmonary venous hypertension)
Pulmonary hypertension associated with respiratory disease and/or hypoxia
COPD, Interstitial lung disease, OSA
Chronic thromboembolic/embolic pulmonary hypertension
Pulmonary hypertension from unclear mechanisms
Journal of the American College of Cardiology
Vol. 62, No. 25, Suppl D, 2013

17. Once pulmonary hypertension is detected, look for causes!
European Heart Journal (2009) 30, 2493–2537

18. Other testing as suggested by H&P
History and Exam
LFT, CBC
Autoimmune screen
Overnight oximetry
Echocardiography
Chest CT
V/Q scan
PFT
HIV serology
Other testing as suggested by H&P
European Heart Journal (2009) 30, 2493–2537

19. PAH (Group 1) Medication Options
Mild Moderate Severe
25 <MPAP< <MPAP< MPAP> 50
Ca++ Channel Blocker X
Endothelin antagonist X X
PDE-5 inhibitor X X
Prostanoids X X
Inhaled iloprost X X
SQ treprostinil X X
IV epoprostenol X X

20. Group 1: “Primary” pulmonary arterial hypertension
Remember PAH (Group 1) and PH (Groups 2-5) are different entities
PAH is a progressive disease with a 50% survival at 2.8 years
Can lead to sudden death
Often affects young adults: mean age 45 years
Rarely familial

21. Group 1: Secondary pulmonary artery hypertension
Collagen vascular disease
scleroderma
Systemic lupus erythematosus
Liver disease
Congenital heart
Drugs/toxins
HIV infection

22. Therapy Treat any underlying disease.
Treat cardiac disease (left sided).
Treat lung disease and hypoxemia.
Treat obstructive sleep apnea or any associated sleep disorder.
Treat thromboembolic disease.
Remember: Groups 2-5 are managed differently and vasodilator therapy is NOT recommended.

23. Intravenous Vasodilators
Pulmonary Arterial
Respiratory Disease
Pulmonary Venous
Increased Shunt
Pulmonary Edema

24. Adjunctive therapy Salt restriction. Diuretics as needed.
Oxygen at rest or with activity.
Flu and pneumococcal vaccination.
Digoxin ? Role if any.
Anticoagulation ?

25. Group 1 PAH therapy

26. Drug of choice? Right heart catheterization vasodilator “challenge”
20% acute drop in MPAP and PVR?
...begin with ca++ channel blocker

27. Right Heart Catheterization and Vasodilator Trial
Acute Responder
Non-Responder
NYHA II-IV
Calcium Channel Blocker
Vasodilator therapy ERA or PDE5-inh
or prostacyclin analog
Not Improved
Improved
Involve a specialist with expertise
Consider combination therapy
Transplant

28. Calcium Channel Blockers
PAH therapy is based on severity of disease as determined by right heart catheterization and responsiveness to vasoactivity testing.
Although not FDA approved for the treatment of PAH, CCBs commonly used are nifedipine, diltiazem, and amlodipine.
All agents are titrated to clinical effect.

29. Objective measures to monitor therapy…every 3-6 months
6 minute walk (goal > 300 meters)
NT-ProBNP (Brain Naturetic Peptide)
Sequential echocardiography
Other studies depending on context

30. …other therapeutic options
If chronic pulmonary emboli…
pulmonary thromboendarterectomy surgery
If all meds fail…
atrial septostomy
organ transplantation
heart-double lung
double lung

31. Riociguat (a stimulator of soluble guanylate cyclase) significantly improved exercise capacity and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension.
N Engl J Med 2013;369:

32. Final “take home” messages
New onset exertional dyspnea…think of pulmonary hypertension.
Screen by Transthoracic Doppler Echo but make sure you tell the cardiologist that you are thinking of PH!
Definitive diagnosis by right heart catheterization.
Several pharmacologic options now available: selection a function of PAH severity, expertise, cost assessment, and other factors.
Pregnancy may cause significant challenges.
PH patients are increasingly older with potential multiple ongoing diagnoses.

33. Thank you so much for the invitation.