Pulm HTN

Question 1

How does PAH affect lung function?

Answer 1

• Impairs gas exchange (dec DLCO)
  -
  Changes distribution of perfusion –> high V/Q areas which means other areas become low V/Q –> low PaO2, high A-a gradient
• Usually inc minute vent so PaCO2 remains normal
• Less active cap-alveoli interface

Question 2

6 Risk Factors

Answer 2

• Family hx
• Congenital heart disease
• Connective tissue disease
• Hx DVT/PE
• Associated w/ old appetite suppressing drug and HIV
• Hx portal HTN

Question 3

Signs and Symptoms

Answer 3

• Symptoms
  
  • Dyspnea
  • Angina (RV enlargement - less blood delivery)
  • Raynaud’s phenomenon
  • Edema
  • Syncope
• Physical Exam
  - RV dilation –> tricupsid regurg b/c annulus inc in size (holo-systolic murmur)
  - Loud S2 (pulmonic in origin) b/c greater pressure difference b/n RV and pulmonary vessels
  - RV lift
  - RV S4
  - May have pulmonic regurg (diastolic)
• May also see signs of R heart fail
  - JVD elevated w/ V wave
  - Edema, ascites, hepatomegaly

Question 4

PAH on Imaging

Answer 4

• CXR -
  
  • Prominent hilar pulmonary arteries (dilated)
  • Peripheral hypo-vascularity; construction of peripheral lung vessels (pruning)
  • May see large RV on lateral image
• CT
  
  • If give contrast - can visualize aorta and main pulm artery diameters (can meas size of pulmonary artery and see if it is larger than aorta); DILATION

Question 5

PAH Pathology

Answer 5

• THICK media w/ very small lumen or complete occlusion
• Remodeling eventually leads to formation of plexiform lesions
• If pressures high enough to destroy artery - necrotizing arteritis (pathonomonic)

Question 6

2 Main Tests / Dx

Answer 6

• Echo - can estimate RV pressure using doppler; can see RV dilation (if RV is equal or > LV)
  
  • Estimate RV systolic pressure using the velocity of tricuspid regurg
• R Heart Cath - gold std for diagnosis (but invasive so only use if high suspicion) - can meas exact pressures

Question 7

How is PAH class I defined objectively?

Answer 7

• Inc PA pressure or mPAP (>25 mmHg)
• Dec cap wedge pressure or PAWP (<15 mmHg)
• inc resistance (>3 Wood units) (PVR = mPAP - PAWP / CO)

Question 8

Cardiovascular Effects

Answer 8

• Inc RV afterload (inc JVP, peripheral edema, hepatomegaly) –> RV failure –> eventual RV remodeling (dilation)
• This can then affect LV
  
  • Dec LV preload (less pumped to L side)
  • RV dilation can reduce LV size and compliance
• LV dysfunction –> dec CO and hypotension (syncope, dizziness, fainting)

Question 9

5 Etiological Groups

Answer 9

• Group I - pulmonary arterial HTN (PAH)
  
  • Ex) Group 1 PAH Associated w/ Scleroderma
    
    • 7-12% of pts w/ scleroderma end up w/ PAH
• Group II - related to L heart disease (most common)
• Group III- associated w/ lung disease or low PO2 (COPD, sleep disordered, high alt, interstitial)
• Group IV - chronic thromboembolic pulmonary HTN (CETPH)
• Group V- miscellaneous; multi-factorial (ex - sickle cell or chronic hemolytic anemia)

Question 10

4 Functional Classes

Answer 10

• I - no limitation of normal activities
• II - Mild limitation; no discomfort at rest; normal physical activity –> dyspnea, fatigue, chest pain, pre-syncope
• III - Marked limitation; no discomfort at rest; less than normal physical activity –> dyspnea, fatigue, chest pain, pre-syncope
• IV - Unable to perform any physical activity; dyspnea, fatigue, pre-syncope at rest; evidence of RV failure; SYNCOPE
  
  • If have syncope then automatically class IV

Question 11

Overall Therapy Options (6)

Answer 11

• Oral anticoagulants
• Diuretics (balance w/ already low CO)
• Oxygen (low flow)
• Digoxin (not used as much anymore) - may inc CO
• Supervised exercise program rehab
• 3 classes of drugs (endothelin receptor antagonists, PDE5 inhibitors, PGI2)

**AMBITION TRIAL - 2 drugs (combo therapy) has better outcomes

Question 12

Bostentan

Answer 12

• Endothelin 1 - prod and released by endo cells –> binds endo cell receptor –> phospholipase C path –> smooth muscle constriction (pulm vasoconstriction)
• SO … MAO - endothelin receptor antagonists –> vasodilation
• PO
• Side Effects = hepatotoxic (monitor LFTs); use CYPs and UGTs

Question 13

Sildenafil & Tadalafil

Answer 13

• NO endogenously prod by endo cells –> smooth muscle layer –> more cGMP –> vasodilation
• PAH pt have reduced eNOS (endothelial nitric oxide synthase) in lungs
• SO… MAO - PDE5 inhibitors block degradation of cGMP –> more vasodilation
• Sildenafil (Viagra), tadalafil (longer-acting - 1/day- Cialis)
• Side Effects = headache, nasal congestion, visual disturbance (PDE6 in retina)

Question 14

Epoprostenol

Answer 14

• Prostacyclins made by endo –> inc cAMP –> relaxes smooth muscle AND inhibit platelet aggregation and dec smooth muscle proliferation
• Prostacycline synthase expression is down-regulated in PAH pt
• SO… give PGI2 which will cause relaxation
• IV so need indwelling cath
• Side Effects = dizziness, headache, jaw pain, flushing OR infection from indwelling cath of epoprostenol OR danger of abrupt withdrawal –> rebound pulm vasoconstriction –> death