PAH

Question 1

How does PAH work?

Answer 1

1. pulmonary arterioles narrow
2. RV dilates
3. pulmonary edema and damage
4. thrombi and/or plexiform lesion formation

Question 2

PH vs. PAH (differences)

Answer 2

PH: MPAP > equal to 20 at rest; more common
PAH: progressive with endothelial dysfunction –> elevated pulmonary arterial pressure and pulmonary vascular resistance; rare

Question 3

what are the WHO PH classifications?

Answer 3

Group 1: PAH
Group 2: LFH
Group 3: LD
Group 4: Chronic thromboembolic pulmonary HTN
Group 5: Pulmonary HTN resulting from unclear mechanisms

Question 4

what are the signs and symptoms of PAH?

Answer 4

early –> present as non-specific resulting in a large differential diagnosis
late –> signs of right-sided HF

Question 5

what is the diagnosis of PAH?

Answer 5

1. echocardiogram
   –> evaluate potential causes, RV function, estimate PAP and PVR
2. right heart catheterization
   –> assess response to pulmonary vasodilators before starting therapy
3. exercise testing
   –> distance walked in 6 min
4. biomarkers
   –> BP & NTproBNP

Question 6

what are the hemodynamic definitions of PAH?

Answer 6

mPAP > 20
PAWP < or equal to 15
PVR > 2 wood units

Question 7

what is the PAWP?

Answer 7

1. estimates left arterial pressure
2. normal 4-12
3. elevated #s signal LV failure or mitral stenosis

Question 8

what is the PVR?

Answer 8

calculated using formula based on mPAP and PAWP

Question 9

what are the WHO functional classifications?

Answer 9

1. WHO FC1
2. WHO FC2
3. WHO FC3
4. WHO FC 4

Question 10

What is the WHO FC1 classifications?

Answer 10

1. no limit of activity
2. ordinary activity does NOT cause any chest pain, dyspnea, ect.

Question 11

What is the WHO FC2 classifications?

Answer 11

1. slight limit of activity
2. comfortable at rest but cause dyspnea, chest pain, ect

Question 12

What is the WHO FC3 classifications?

Answer 12

1. marked limitation of activity
2. comfortable at rest and less than ordinary dyspnea, chest pain, ect.

Question 13

What is the WHO FC4 classifications?

Answer 13

1. cant do anything

Question 14

what are the guidelines of treatment with PAH pts without comorbidities?

Answer 14

RISK 3
if low or interm risk
– initial ERA + PDE5i therapy
if high risk
– initial ERA + PDE5i + PCA
RISK 4
if low risk
– continue initial therapy
if interm-low risk
– add PRA OR
– switch from PDE5i to sGCs
if high or interm-high risk
– add iv or sc PCA and/or evaluate lung transplant

Question 15

what are the guidelines of treatment with PAH pts with comorbidities?

Answer 15

1. initial oral monotherapy with PDE5i or ERA

Question 16

what is a vasoreactivity test?

Answer 16

positive test = drop in mPAP > 10 w/PAP < 40 w/stable improved cardiac output

Question 17

when can you use a CCB and does it guarantee a response?

Answer 17

1. positive test does not guarantee response to CCB therapy and patents should be continually assess (symptoms and RHC) for response
2. use only when vasoreactive +

Question 18

what CCBs do you use?

Answer 18

-LA nifedipine or diltiazem
- amlodipine
- NO verapamil due to inotropic effects

Question 19

what are the adverse reactions for PDE-5 inhibitors?

Answer 19

hearing loss, sudden vision loss, hypotension

Question 20

what is important to know about a soluble guanylate cyclase stimulator?

Answer 20

RIOCIGUAT
- cannot be used with PDE5 due to risk of hypotension

Question 21

what are the ERAs?

Answer 21

bosentan (mixed)
ambrisentan (ETa selective)
macitentan (mixed)

Question 22

how long does it take ERA to work?

Answer 22

8-10 weeks

Question 23

what are the prostacyclin medications?

Answer 23

epoprostenol IV
treprostinol (all the above)
selexipag ( po agonist)

Question 24

what are the ADRs for prostacyclins?

Answer 24

thrombocytopenia and hypotension

Question 25

what are the inhaled prostacyclins?

Answer 25

treprostinol (tyvaso and tyvaso DPI)

Question 26

what is special about treprostinil?

Answer 26

dosing always based of weight when initiating the drug

Question 27

what is special and important to know about epoprostenol IV?

Answer 27

t1/2 of 3-5 minutes must ALWAYS have back up cassette prepared dosing ALWAYS based off of weight when initiating drug

Question 28

what was the conclusion of the ambition trial?

Answer 28

if patient candidate for initial combo therapy and is WHO class 2 or 3, then ERA + PDE5i as initial therapy will result in less clinical feature

Question 29

what are some cardiopulmonary comorbidities?

Answer 29

CV: obesity, HTN, diabetes, CAD Pulmonary: lung disease (fibrotic lungs)

Question 30

what is sotatercept-csrk (winrevair)? what is its action and pk note?

Answer 30

ACTION: --> activin signaling inhibitor --> fusion protein with ActR2a and human IgG Fc --> acts as ligand trap for TGF-b superfamily PK NOTE: --> given SQ q24d and require reconstitution --> avg. peak 7 day and HL of 24h

Question 31

what is sotatercept-csrk (winrevair)? what is its AEs and use?

Answer 31

USE: --> PAH to inc. excersie capacity, inc. functional class and dec. risk of clinical worsening events AEs: --> thrombocytopenia, HA, serious bleeding, emryo-fetal harm

Question 32

what are some general considerations in terms of physical activity?

Answer 32

be active within symptom limits

Question 33

what are some general considerations in terms of anticoag?

Answer 33

- no recom against - inc. risk of bleeding but could be beneficial

Question 34

what are some general considerations in terms of diuretics?

Answer 34

may be used once HF - monitor kidney and weight

Question 35

what are some general considerations in terms of O2?

Answer 35

may be used when symptomatic and desaturation on exercise

Question 36

what are some general considerations in terms of anemia and iron?

Answer 36

IV iron needed Hgb <7 and ferritin < 100 or 100-299 ferritin and transferrin sat < 20%

Question 37

what are some general considerations in terms of vaccines?

Answer 37

NO flu, strep, pneomonia, covid

Question 38

what are some special considerations for prego and birth control?

Answer 38

1. no in prego 2. safe: CCBs, PDE5, prostacyclins 3. NO: ERA, riociguat, selexipag 4. contraception safe