16: Pulmonary Hypertension

Question 1

Pulmonary vasculature characteristics

Answer 1

• High flow, low resistance: PVR ~1/15 of SVR due to large cross-sectional area
• High capacitance: can accomodate ↑CO
• Arterioles offer very little resistance

Question 2

Physiologic causes of PHTN

Answer 2

• PHTN: mean P_PA ≥ 25 mmHg (normal = 14)
• P_PA = (CO x PVR) + P_LA
  
  • _​↑CO: congenital heart defects w/ L-R shunt, cirrhosis, anemia, AV malformations
  • ↑PLA: LVF, mitral valve dz, restrictive cardiomyopathy
  • ↑PVR: destruction/obliteration of pulmonary vascular bed (ILD, PE), hypoxic vasoconstriction (COPD, high altitude), small pulmonary artery/areteriole vasculopathy (PAH)

Question 3

Pulmonary Arterial Hypertension (PAH)

Answer 3

• Mean PAP ≥ 25mmHg + PCWP/LVEDP ≤ 15mmHg
  
  • Indicates normal pressure in L heart
• Triggering lesion is intrinsic arteriopathy
  
  • Idiopathic PAH
  • Heritable
  • Drug/toxin-induced
  • Persistent PH of newborn
  • Associated w/ CTD, HIV, portal HTN, CHD, schistosomiasis, chronic hemolytic anemia

Question 4

Classifications of PH

Answer 4

1. Pulmonary arterial hypertension
2. PH due to L heart dz
3. PH due to lung dz and/or hypoxia
4. Chronic thromboembolic PH
5. PH w/ unclear multifactorial mechanisms

Question 5

PAH vascular pathology

Answer 5

• Fibrotic and proliferative lesions in muscular arteries of less than 500 um diameter
• Medial hypertrophy
• Intimal thickening/fibrosis
• In situ thrombosis
• Plexiform lesion: focal intimal thickening followed by exuberatn endothelial cell proliferation

Question 6

Homeostatic imbalances in PAH

Answer 6

• ↑Endothelin-1
• ↓Prostacyclin
• ↓Nitric oxide

Leads to vasoconstriction, prothrombosis, cell proliferation

Question 7

Therapeutic targets for PAH

Answer 7

1. Endothelin-receptor antagonists
2. Exogenous NO
3. Phosphodiesterase type 5 inhibitor
4. Prostacyclin derivatives

Question 8

Top 5 associated causes of PAH

Answer 8

1. Connective tissue/collagen vascular dz (scleroderma)
2. Congenital heart dz
3. Portopulmonary dz (portal HTN)
4. Drugs/toxins
5. HIV

Question 9

Right ventricle in PAH

Answer 9

• Embryologically different from LV: arise from different embryological origins
• Structurally different from LV: LV concentric, RV crescent; RV LV free wall ~8-11mm, RV ~2-3mm; RV lacks circumferential constrictor fibers
• Functionally different from LV: RV more compliant, myocardial energy expenditure ~1/5th that of LV
• RV dilatation –> IV septum bulging into LV –> impaired LV filling/stroke volume

Question 10

PAH clinical presentation

Answer 10

• Dyspnea
• Fatigue
• Syncope/near syncope
• Chest pain
• Palpitations
• Leg edema

Question 11

PAH risk factors

Answer 11

• FHx
• Prematurity
• Connective tissue dz
• Congenital heart dz
• Portal HTN
• Environmental/drug factors
• HIV

Question 12

PAH PEX findings

Answer 12

• Accentuated pulmonary component of S2
• Early systolic click
• Midsystolic ejection murmur
• Left parasternal lift
• RV S4
• Increased jugular a wave

Question 13

PAH CXR findings

Answer 13

• Peripheral hypovascularity (pruning)
• RV enlargement into retrosternal clear space
• Prominent proximal pulmonary arteries

Question 14

Chronic thromboembolic pulmonary hypertension (CTEPH)

Answer 14

• Curable form of PH
• Group IV PH

Question 15

Cardiac catheterization

Answer 15

• Gold standard of PH
• Exclude CHD
• Measure wedge pressure or LVEDP
• Establish severity and prognosis
• Test vasodilator therapy
• Hemodynamics:
  
  • Pulmonary venous HTN: ↑PCWP, normal PVR
  • PAH, PH w/ respiratory dz, CTEPH: normal PCWP, ↑PVR

Question 16

Optimal treatment strategy

Answer 16

Anticoagulants + diuretics + oxygen + digoxin

Question 17

Acute vasoreactivity testing

Answer 17

• Administer short-acting vasodilator (epoprostenol, adenosine, NO)
• Acute robust responder: ↓mPAP by > 10 mmHg to absolute value of < 40 mmHg, without concurrent drop in CO
  
  • More likely to have sustained beneficial response to high dose calcium channel blockers (CCB)

Question 18

Calcium channel blockers

Answer 18

• Diltiazem & **Verapamil **
• Give to acute robust responders

Question 19

Prostanoids

Answer 19

• **epoprostenol **(IV)
• stimulate adenylate cyclase –> ↑cAMP –> vasodilation, antiproliferation, platelet aggregation inhibition
• improved hemodynamics, functional capacity and survival
• SFx: jaw pain, delivery system problems

Question 20

Phosphodiesterase-5 inhibitors

Answer 20

• **Sildenafil **(PO, IV)
• Inhibition of cGMP-specific phosphodiesterase –> vasodilation and antiproliferation
• improve hemodynamics and functional capacity

Question 21

Endothelin receptor antagonists

Answer 21

• **Bosentan **(PO)
• ETA, ETB receptors expressed on SMCs and cardiac myocytes; activation –> vasoconstriction and proliferation of vascular SMCs
• improve hemodynamics and functional capacity
• SFX: liver toxicity, teratogenic, peripheral edema, anema

Question 22

Pulmonary vasodilator considerations

Answer 22

• Decrease SVR –> systemic HoTN
• Worsen V/Q mismatch –> hypoxemia
• Abrupt med withdrawal –> rebound PH
• ↑pulmonary capillary pressure –> edema
• SFx: HA, dizziness, flushing, nasal congestion

Question 23

General treatment measures for PH

Answer 23

• Optimize preload: diuretics, salt restriction
• Supplemental O2
• Anticoagulation
• Digoxin
• Cardiopulmonary rehab: ↑functional capacity

Question 24

Surgical therapies for PH

Answer 24

• Atrial septostomy: unload RV at cost of hypoxemia
• Pulmonary thromboendarectomy: for CTEPH
• Lung transplant