PAH

Question 1

PAH

Answer 1

Progressive disease involving endothelial dysfunction–> elevated arterial pressure and pulmonary vascular disease

Question 2

WHO Classification

Answer 2

Group 1: PAH

Causes: unknown, genetic, drug and toxin exposure, disease associated with PAH: CHD, HIV, connective tissue disorders

Treatment: meds specifically for PAH, CCB, Lung transplantation

Question 3

PAH Epidemiology

Answer 3

Rare: 2-7.6 cases per million adults/year

Variable age at diagnosis: mean 50 +/- 14 years, 4 x more common in women

Underrecognized: median 1.1 years to diagnostic right heart catheterization, 1 in 5 symptomatic > 2 years before diagnosis

Question 4

PAH Epidemiology Group 1

Answer 4

prognosis is poor but improving

approx 15% mortality within 1 year

median survival 6 years

negative predictors: poor exercise capacity, high right atrial pressure, right ventricular dysfunction, low cardiac output

Question 5

Diagnosis

Answer 5

Echocardiogram

Right heart catheterization

Question 6

Effects of PAH

Answer 6

Right side of heart has difficulty pumping against high pulmonary pressures

Leads to right heart ventricular failure

Question 7

PAH disease progression

Answer 7

Vascular injury:
Endothelial dysfunction
Decrease NO synthase
Decrease prostacyclin production
Increase thromboxane production
Increase endothelin 1 production

Question 8

Goals of therapy

Answer 8

alleviate symptoms

improve quality of life

prevent or delay disease progression

reduce hospitalization

improve survival

Question 9

AVT

Answer 9

Acute vasoreactivity testing=positive responder=CCB

Acute vasoreactivity testing=negative responder, RV failure, or CCB contraindication= Do not use CCB

Question 10

Acute vasoreactivity test

Answer 10

agents used include: inhaled NO, IV epoprostenol

positive test= drop in mPAP > 10 mmHg with PAP less than 40 mmHg with stable-improved cardiac output

Question 11

WHO FC 1

Answer 11

Treatment naive PAH patients with WHO FC 1= continued monitoring for disease progression=determine when to start therapy

consider CCB if responder

monitor closely and consider initiation of worsening symptoms

Question 12

WHO FC 2

Answer 12

Treatment naive PAH WITH WHO FC 2= Tolerate combo therapy?= Yes, ambrisentan + tadalafil

Cannot tolerate combo then ERA, RIOCIGUAT, PDE-5 INHIBITOR

Question 13

WHO FC 3

Answer 13

Treatment naive PAH with WHO FC 3 W/O rapid disease progression or poor prognosis= Tolerate combo?= Ambrisentan + tadalafil

No: monotherapy= ERA, riociguat, or PDE-5 inhibtor

Question 14

Nitric oxide pathway

Answer 14

PDE-5 inhibitors: sildenafil, tadalafil
Soluble guanylate cyclase stimulator: riociguat

Question 15

Endothelin pathway

Answer 15

Endothelin Receptor Antagonists: bosentan, ambrisentan, macitentan

Question 16

Prostacyclin Pathway

Answer 16

epoprostenol (IV)
iloprost (inhalation)
treprostinil (IV, SQ, inh, oral)

IP prostacyclin receptor agonist: selexipag

Question 17

Phosphodiesterase Inhibitors

Answer 17

decreases conversion of cGMP to GMP
Increased levels of cGMP=pulmonary vasodilation

may used as monotherapy or in combo with other classes

considered first line in FC 2 OR 3 without rapid progression

Question 18

Endothelin Receptor Antagonists

Answer 18

ET receptors on vascular smooth muscle mediate vasoconstriction

Overexpression f ET-1 in PH patients, correlates with remodeling

Blocking ET–> vasodilation

Options in class 2-4

Tadalafil + ambrisentan combo first line for class 2 and class 3 without rapid progression

Improve in 6MWD, pro-BNO, delay time to clinical worsening, optimize hemodynamics

Question 19

ERA adverse events

Answer 19

peripheral edema

LFT abnormalities

Anemia

BBW: embryo-fetal toxicity

REMS: reproductive harm and hepatotoxicity (bosentan)

Question 20

Clinical effects

Answer 20

improvement not likely seen for 8-10 weeks

hemodynamic parameters

exercise capacity

time to clinical worsening

Question 21

Soluble guanylate cyclase stimulator

Answer 21

Riociguat

May be used as alternative to PDE-5i

cannot be used in combo with tadalafil or sildenafil due to risk of hypotension

improves exercise capacity, WHO FC, and time to clinical worsening

Question 22

AMBITION

Answer 22

reason the guidelines changed

Question 23

TRITON

Answer 23

triple therapy vs. dual therapy in naive PAH group 1 patients

triple therapy and dual therapy showed no difference

Question 24

WHO FC 3 WITH RAPID PROGRESSION OR POOR PROGNOSIS or WHO FC 4

Answer 24

Candidate for parenteral prostanoids? Yes= SC treprostinil, IV treprostinil, IV epoprostenol

Not a candidate for parenteral= inhaled or oral prostanoid in combo with ERA + PDE-5i

Question 25

Prostacyclins

Answer 25

inhibit platelet aggregation

Question 26

Prostacyclin ADR

Answer 26

headache, jaw pain, limb pain, flushing/skin rash, diarrhea , N/V, thrombocytopenia

IV: line infections, erthemia

Question 27

Treprostinil IV/SQ

Answer 27

IV infusion requires stable access, do not co-infuse with anything else

SQ is preferred as it avoids risk of central lines

Question 28

Adjunct therapy

Answer 28

Anticoagulation may consider depending on cardiac function

warfarin: INR goal 1.5-2.5

ASA: 81 mg daily