Lecture 3 - Pulmonary Arterial Hypertension

Question 1

What can cause pressure in the Pulmonary Artery to inc?

Answer 1

Changes in the blood vessel

Question 2

What can cause pressure in the Pulmonary Vein to inc?

Answer 2

Changes in the heart

Question 3

What is Pulmonary Arterial Hypertension?

Answer 3

High BP in lungs
MAP > 25

Often leads to right sided HF
Median survival rate after diagnosis w/o treatment is 2.8yrs

Question 4

WHO-E Group I

Answer 4

Idiopathic = cant determine reason for PAH

Associated w/ (APAH)

1. collagen vascular disease = lupus
2. Portal hypertension secondary to liver failure
3. HIV infection
4. Drugs/toxins = stimulants, diet pills, PPA

Question 5

WHO-E Group 2

Answer 5

Pulmonary Hypertension owing to Left Heart Failure

1. Systolic Dysfunction
2. Diastolic Dysfunction
3. Valvular disease

• Most common cause for PAH *

Question 6

WHO-E Group 3

Answer 6

PH Associated w/ Lung disease or Chronic Hypoxemia

COPD
ILD
ONA
Chronic exposure to high altitudes

Question 7

WHO-E Group 4

Answer 7

Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic disease
Pulmonary Embolism

Question 8

WHO-E Group 5

Answer 8

Unclear or multifactorial causes

Question 9

Symptoms of PAH

Answer 9

1. Dizziness and/or fainting
2. Shortness of Breath
3. Chest pain
4. Feeling tired/worn out
5. Swollen ankles and legs

Question 10

WHO-F Functional Classes

Answer 10

F-1 (best) - F-4 (worse)

Question 11

F-1

Answer 11

No SOB/fatigue present at rest or with usual physical activity

Question 12

F-2

Answer 12

No SOB/fatigue at rest but one or both present with usual physical activity

Question 13

F-3

Answer 13

No SOB/fatigue at rest but one or both present with simple activities of daily living

Question 14

F-4

Answer 14

SOB/Fatigue present at rest, nearly impossible to complete activates of daily living

Question 15

Gold Standard Diagnostic for PAH

Answer 15

Right Heart Catheterization

Measuring MAP

Question 16

6 minute walk test…

Answer 16

measures patients functional capacity

Question 17

Goals of Pharmacotherapy

Answer 17

1. increase 6 min walk time
2. Reduce WHO functional class
3. Avoid drug-associated adverse effects
4. Reduce mortality

Question 18

Conventional Pharmacotherapy for PAH

Answer 18

Oxygen
Loop Diuretics
Digoxin

Anticoagulants…usually warfarin

Question 19

Positive Response in Acute Vasodilator Trial

Answer 19

Given 5min of NO

Positive response = Decrease in mPAP > 10 mmHG AND to a value of less than 40 mmHG

Question 20

If positive response, Diltiazem dose is….

Answer 20

120mg/day with weekly titration by 120mg/day up to max of 480 mg/day

if SBP < 90, reduce by 120mg/day
if HR < 50, change to LA nifedipine

Question 21

Phosphodiesterase Inhib doses

Answer 21

Sildenafil, 20mg TID (Revatio)

Tadalafil, 40mg QD (Adcirca)

Question 22

Sildenafil PAH info

Answer 22

No difference in 6MWT between doses, don’t inc doses

SE:
Headache, Flushing, Nasal congest, Blurred Vision

• Don’t admin nitrates concomitantly*

Question 23

Endothelial Receptor Antagonists

Answer 23

Bosenten (Tracleer)

Ambrisenten (Letairas)

Question 24

Bosenten (Tracleer) info

Answer 24

Mechanism: Dual ET-A/ET-B antagonist

Starting dose: 62.5mg BID
Max Dose: 250mg BID

can titrate up, see benefit in 6MWT w/ inc dose

11% incidence of hepatotoxicity

Question 25

Ambrisenten (Letairas) info

Answer 25

Mechanism: Selective ET-A antagonist

Starting Dose: 2.5 mg qd
Max dose: 10 mg QD

Question 26

Does Bosenten have data to benefit in WHO-E Group 2

Answer 26

No

Question 27

Blocking Prostacyclin Synthase expression

Answer 27

Epoprostenol (Flolan)

Treprostinil ( Remodulin = IV, Tyvaso = Inhaled)

Question 28

Epoprostenol Dosing

Answer 28

1/2 life = 3 min
Starting Dose = 3ng/kg/min
Target = 30 ng/kg/min

Titrate: Every 1hr by 1ng/kg, every 15min when dec

Question 29

Treprostinil Dosing

Answer 29

1/2 life = 20 min
Starting Dose = 1.25 ng/kg/min
Target Dose = 12.5 ng/kg/min

Titrate: every 3 day, 1 day when dec

Question 30

Dose limiting effects of Epoprostenol

Answer 30

Neuro: Headache, muscoloskeletal pain
cardiac: Hypotension, bradycardia
GI: Diarrhea
Other: Flushing

Question 31

Treprostinil vs Epoprostenol admin

Answer 31

Treprostinil:
SubC = no central lines

Epoprostenol:
Central line = more infections

Question 32

PAH Treatment Algorithm 1

Answer 32

1. O2 + diuretics
   (Dig +/- Aldosterone Inhib în pt w/ BL CHF, nitratres în pt with IHD)
2. Chronic anticoagulants, usually warfarin
3. Positive to Right Heart Cath/vasodilation testing = Diltiazem
4. Negative to Right Heart Cath/vasodilation testing =

Question 33

If don’t have Vasodilator Trial, Group 1 WHO-F Class 1 - 3 give them….

Answer 33

E-1 RA

go to higher dose after 1 month no improvement

Question 34

If don’t have Vasodilator Trial, Group 2 WHO-F Class 1-3

Answer 34

PDE-5 inhibit, fixed dose

Question 35

If don’t have Vasodilator Trial, Group 3/4 WHO F Class 1-3

Answer 35

E-1 RA

Question 36

If don’t have Vasodilator Trial, Group 1,3,4 WHO F Class 2-3

Answer 36

add PDE-5 inhibt

Question 37

If don’t have Vasodilator Trial, Group 1-4, WHO F Class 4

Answer 37

add Prostacyclin Analog to existing 1st & 2nd line therapy

Question 38

If don’t have Vasodilator Trial, Group 2, WHO F Class 2

Answer 38

add E-1 RA

Question 39

Pts who has rapidly worsening PAH moves up from WHO-F Class 2 - 3 in less than 2 weeks then….

Answer 39

Start prostacyclin analog therapy immediately

consider adding E-1 RA or PDE-5 if still symptoms or continue if already on them

Question 40

How long to redo 6MWT?

Answer 40

~ 1 month