Lecture 19: Pulmonary Hypertension

Question 1

Ppa equation

Answer 1

(CO x PVR) + Pla (Pla = pressure of LA)

Question 2

Psa equation

Answer 2

(CO x SVR) + Pra (Pra = pressure of RA)

Question 3

What is the definition of pulmonary hypertension

Answer 3

Ppa great than 25 mm Hg

Question 4

Three causes of pulmonary hypertension

Answer 4

Increased CO, increased Pla, increased PVR

Question 5

Three reasons for increased PVR

Answer 5

Destruction of pulmonary vascular bed (ILD, emphysema, PE), hypoxic vasoconstriction (COPD, high altitude), small pulmonary artery/arteriole vasculopathy (PAH)

Question 6

What is PAH? Describe/define

Answer 6

Pulmonary arteriole hypertension –> fibrotic/proliferative lesions in muscular arteries

Question 7

Progression of PAH histologically (4)

Answer 7

Medial hypertrophy –> intimal thickening –> in situ thrombosis and plexiform lesion

Question 8

Pathogenesis of PAH (3 pathways)

Answer 8

Upregulated endothelin pathway; downregulated NO pathway, decreased prostacyclin pathway

Question 9

Four causes of PAH

Answer 9

1. Idiopathic (~50%); 2. Heritable (BMPR2 mutation w/ 20% penetrance); 3. Drug and toxin induced; 4. Associated PAH (~50%)

Question 10

Five Associated PAH diseases

Answer 10

Connective tissue disorders (~50%), congenital heart disease (high pressure/flow –> endothelial dysfunction), portal hypertension, HIV, schisotomiasis

Question 11

Is PAH common?

Answer 11

Nope! 5-15 cases per 1 million

Question 12

Median survival of untreated PAH

Answer 12

2.8 years

Question 13

What happens to the RV if you “clamp” the pulmonary artery? What does this mean?

Answer 13

It fails quickly (decrease in SV) –> cannot handle increases in pressure

Question 14

Does the RV have isovolmic contraction/relaxation? How can we create this?

Answer 14

No (more efficient: ejects blood while contraction and fills while relaxing); pulmonic stenosis makes RV behave like LV

Question 15

Three consequences of increased RV afterload and their consequences. Ultimate consequence?

Answer 15

Increased RV wall stress (–> RV ischema); decreased RV output (–> decrased LV output); increased RV dilation (increased leftward septal shift and regurge); cardiogenic shock

Question 16

Symptoms of PAH (2 main classes)

Answer 16

Low perfusion: dyspnea, fatigue, chest pain, palpitations, lightheadedness, syncope; Congestion: abdominal pain and fullness, peripheral edema

Question 17

Physical exam of PAH (5), including heart findings (6)

Answer 17

Hypoxemia, tachycardia, hypotension, JVD, symptoms of RV failure; Heart findings: RV heave, split S2, systolic TR murmur, diastolic PR murmur, RV S3, RV S4

Question 18

What is a RV heave a sign of?

Answer 18

RV dilatation

Question 19

A split S2 will have a loud A2 or P2 in PAH

Answer 19

P2

Question 20

Is PAH associated with pulmonary edema? Why?

Answer 20

NO: no significant rales because resistance is PRIOR to capillaries in pulmonary vasculature, so capillary pressures are low

Question 21

ECG in PAH (3)

Answer 21

RV hypertrophy/strain, incomplete/complete right bundle branch block, right atrial enlargement

Question 22

What procedure can confirm the presence of pulmonary hypertension?

Answer 22

Right heart catheterization

Question 23

If you wedge pressure is high (greater than 15 mm Hg), what is this consistent with?

Answer 23

Left sided disease

Question 24

If you wedge pressure is low (less than 15 mm Hg), what is this consistent with?

Answer 24

Precapillary disease

Question 25

Natural history of pulmonary hypertension

Answer 25

Over time with elevated pulmonary pressure, CO begins to drop because of RV heart failure; PVR will continue to rise and CO continues to fall (low perfusion sx); overtime, Pap will fall but Rap will rise (congestion sx)

Question 26

Tx for PAH (5 meds/classes)

Answer 26

Ca2+ channel blockers; prostanoids; endothelial receptor antagonists; PDE-5 inhibitors; riociguat

Question 27

When are Ca2+ channel blockers helpful for PAH? % patients?

Answer 27

If positive vasoreactivity test = able to vasodilate w/ administered vasodilator because this suggests a MUSCULAR problem; 13%

Question 28

Prostanoids: mechanism and drugs

Answer 28

Stimulates adenylate cyclase --> increased cAMP --> vasodilation, antiproliferation, platelet aggregation inhibition; epoprostenol (IV), treprostinil (SC, IV, PO inhalation), iloprost (inhalation)

Question 29

What is the only PAH medication with a proven survival benefit? What's an important note about this medication?

Answer 29

Epoprostenol; require continuous IV administration

Question 30

Effects of prostanoids

Answer 30

Improve hemodynamics, functional capacity and survival

Question 31

Which has the longer half life, epoprostenol or trepostinil?

Answer 31

Trepostinil

Question 32

Endothelin receptor antagonists: mechanism

Answer 32

Activation of ETA and ETB receptors --> sustained vasoconstriction and proliferation of vascular smooth muscle cells; ETB receptors also mediate pulmonary ET clearance and induce endothelial cell production of local mediators of vascular tone (NO, prostacyclin); SO you want to block A not B

Question 33

Endothelin receptor antagonists: medicatons

Answer 33

Bosentan (PO), ambrisentan (PO), macitentan (PO)

Question 34

Phosphodiesterase-5 inhibitors: mechanism

Answer 34

Inhibition of cGMP-specific phosphodiesterase; | vasodilation, antiproliferation, platelet aggregation inhibition --> improve hemodynamics and functional capacity

Question 35

PDE-5: medications (2)

Answer 35

Sildenafil (PO, IV), tadalafil (PO)

Question 36

Riociguat: mechanism

Answer 36

Stimulates soluble guanylate cyclase (sGC) --> sGC converts GTP to cGMP; vasodilation, antiproliferation, platelet aggregation inhibition --> improves hemodynamics and functional capacity

Question 37

Cautions for use of pulmonary vasodilators

Answer 37

Decrease SVR --> system hypotension; abrupt medication withdrawal --> rebound pulmonary hypertension; worsen V/Q matching --> hypoxemia; increase pulmonary capillary pressure --> pulmonary edema

Question 38

Why do you get worse V/Q matching with pulmonary vasodilators? Who is this important for? What is a fix?

Answer 38

Pulmonary vasodilator will dilate areas of the lung that might be poorly ventilated; those with lung disease; give medication via inhalation

Question 39

Who do you avoid pulmonary vasodilators with? Why?

Answer 39

Those with elevated left atrial pressures; at risk for pulmonary edema because if you decrease the pre-capillary constriction, you increase the pressure in the avleoli which cannot be tolerated by the high pressure LA

Question 40

SEs of pulmonary vasodilators

Answer 40

Vasodilation: headache, dizziness, flushing, nasal congestion; ERAs: teratogenic, peripheral edema, anemia; bosentan: liver toxicity; prostanoids: jaw pain, delivery system problems (subcutaneous and intravenous)

Question 41

PAH: general treatment measures (4)

Answer 41

Supplemental O2, anticoagulation, digoxin (improved contractility), cardiopulmonary rehab (improve fxnl capacity)

Question 42

PAH: surgical therapies (3)

Answer 42

Atrial septostomy (unloads RV, but hypoexmia results); pulmonary thromboendarectomy (patients with CTEPH); lung transplant

Question 43

Pulmonary HTN: WHO Classificiations

Answer 43

1: PAH; 2: Left heart; 3: Lung disease; 4: Chronic thromboembolic pulmonary HTN; 5: Misc