Lecture 3 - Pulmonary Arterial Hypertension Flashcards
What can cause pressure in the Pulmonary Artery to inc?
Changes in the blood vessel
What can cause pressure in the Pulmonary Vein to inc?
Changes in the heart
What is Pulmonary Arterial Hypertension?
High BP in lungs
MAP > 25
Often leads to right sided HF
Median survival rate after diagnosis w/o treatment is 2.8yrs
WHO-E Group I
Idiopathic = cant determine reason for PAH
Associated w/ (APAH)
- collagen vascular disease = lupus
- Portal hypertension secondary to liver failure
- HIV infection
- Drugs/toxins = stimulants, diet pills, PPA
WHO-E Group 2
Pulmonary Hypertension owing to Left Heart Failure
- Systolic Dysfunction
- Diastolic Dysfunction
- Valvular disease
- Most common cause for PAH *
WHO-E Group 3
PH Associated w/ Lung disease or Chronic Hypoxemia
COPD
ILD
ONA
Chronic exposure to high altitudes
WHO-E Group 4
Chronic Thromboembolic Pulmonary Hypertension
Chronic thromboembolic disease
Pulmonary Embolism
WHO-E Group 5
Unclear or multifactorial causes
Symptoms of PAH
- Dizziness and/or fainting
- Shortness of Breath
- Chest pain
- Feeling tired/worn out
- Swollen ankles and legs
WHO-F Functional Classes
F-1 (best) - F-4 (worse)
F-1
No SOB/fatigue present at rest or with usual physical activity
F-2
No SOB/fatigue at rest but one or both present with usual physical activity
F-3
No SOB/fatigue at rest but one or both present with simple activities of daily living
F-4
SOB/Fatigue present at rest, nearly impossible to complete activates of daily living
Gold Standard Diagnostic for PAH
Right Heart Catheterization
Measuring MAP
6 minute walk test…
measures patients functional capacity
Goals of Pharmacotherapy
- increase 6 min walk time
- Reduce WHO functional class
- Avoid drug-associated adverse effects
- Reduce mortality
Conventional Pharmacotherapy for PAH
Oxygen
Loop Diuretics
Digoxin
Anticoagulants…usually warfarin
Positive Response in Acute Vasodilator Trial
Given 5min of NO
Positive response = Decrease in mPAP > 10 mmHG AND to a value of less than 40 mmHG
If positive response, Diltiazem dose is….
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
Phosphodiesterase Inhib doses
Sildenafil, 20mg TID (Revatio)
Tadalafil, 40mg QD (Adcirca)
Sildenafil PAH info
No difference in 6MWT between doses, don’t inc doses
SE:
Headache, Flushing, Nasal congest, Blurred Vision
- Don’t admin nitrates concomitantly*
Endothelial Receptor Antagonists
Bosenten (Tracleer)
Ambrisenten (Letairas)
Bosenten (Tracleer) info
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
Ambrisenten (Letairas) info
Mechanism: Selective ET-A antagonist
Starting Dose: 2.5 mg qd
Max dose: 10 mg QD
Does Bosenten have data to benefit in WHO-E Group 2
No
Blocking Prostacyclin Synthase expression
Epoprostenol (Flolan)
Treprostinil ( Remodulin = IV, Tyvaso = Inhaled)
Epoprostenol Dosing
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
Treprostinil Dosing
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
Dose limiting effects of Epoprostenol
Neuro: Headache, muscoloskeletal pain
cardiac: Hypotension, bradycardia
GI: Diarrhea
Other: Flushing
Treprostinil vs Epoprostenol admin
Treprostinil:
SubC = no central lines
Epoprostenol:
Central line = more infections
PAH Treatment Algorithm 1
- O2 + diuretics
(Dig +/- Aldosterone Inhib în pt w/ BL CHF, nitratres în pt with IHD) - Chronic anticoagulants, usually warfarin
- Positive to Right Heart Cath/vasodilation testing = Diltiazem
- Negative to Right Heart Cath/vasodilation testing =
If don’t have Vasodilator Trial, Group 1 WHO-F Class 1 - 3 give them….
E-1 RA
go to higher dose after 1 month no improvement
If don’t have Vasodilator Trial, Group 2 WHO-F Class 1-3
PDE-5 inhibit, fixed dose
If don’t have Vasodilator Trial, Group 3/4 WHO F Class 1-3
E-1 RA
If don’t have Vasodilator Trial, Group 1,3,4 WHO F Class 2-3
add PDE-5 inhibt
If don’t have Vasodilator Trial, Group 1-4, WHO F Class 4
add Prostacyclin Analog to existing 1st & 2nd line therapy
If don’t have Vasodilator Trial, Group 2, WHO F Class 2
add E-1 RA
Pts who has rapidly worsening PAH moves up from WHO-F Class 2 - 3 in less than 2 weeks then….
Start prostacyclin analog therapy immediately
consider adding E-1 RA or PDE-5 if still symptoms or continue if already on them
How long to redo 6MWT?
~ 1 month
