Twenty Nine

Question 1

What is PVR like compared to SVR? What happens in hypoxia?

Answer 1

 In keeping with these low pressures,

 the walls of the pulmonary artery and its branches are

remarkably thin

 contain relatively little smooth muscle

 Lungs accept whole cardiac output as PVR

resistance is only one-tenth that of the systemic

circulation in normal conditions

 PVR increases with alveolar hypoxia because of

constriction of small pulmonary arteries

Question 2

How is pulmonary hypertension clinically defined? What are the 5 different groups?

Answer 2

 Mean pulmonary-artery pressure of more than 25
mm Hg at rest

 Group I

Pulmonary arterial hypertension (PAH)

 Group II

Pulmonary venous hypertension due to left heart disease

 Group III

Pulmonary hypertension owing to lung diseases and/or

hypoxia

 Group IV

Chronic thromboembolic Pulmonary hypertension (CTEPH)

 Group V

Pulmonary hypertension with unclear multifactorial

mechanisms

Question 3

How is group I hemodynamically defined?

Answer 3

 Mean pulmonary artery pressure(mPAP) > 25 mm Hg

 Pulmonary Artery Wedge Pressure (PCWP) ≤ 15 mm Hg

 Pulmonary Vascular Resistance (PVR) > 3 Wood units

Question 4

What are the pathological changes in PAH?

Answer 4

Medial hypertrophy Intimal thickening

Plexiform lesions

Arteriolar occlusion

Question 5

What is a genetic mutation associated with PAH? How does the genetic association work?

Answer 5

 Mutations in bone morphogenetic protein type II
receptor (BMPR2) or activin receptor-like kinase-1
(ALK-1 are emerging as determinants of severity of
PAH.

 Mutations in BMPR2 have been reported in

more than 70% of subjects with 1 or more

affected relatives (heritable PAH)

Without any genetic component, even initiators of pulmonary hypertension won’t do much, but with the mutation, an individual will be much more reactive to the initiators.

Question 6

What are various vascular mediators of PAH? Why are these significant?

Answer 6

decreased NO, decreased PGI2, Increased endothelin

They are what the drugs target.

Question 7

What are some presenting symptoms of PAH? How is the diagnosis of IPAH made? What will be seen on Xray? What is the best tool for screening for PAH? What is the gold standard for diagnosing PAH?

Answer 7

 Diagnosis
 IPAH is by exclusion

 Presenting Symptoms
 Dyspnea (60%) 
 Syncope 
 Fatigability
 Angina 
 Edema

Enlarged pulmonary arteries

Screening with echocardiogram/doppler is the best tool for screening
 Estimates the RA-RV pressure gradient
- measures the tricuspid systolic peak velocity (TR)
Using a modified Bernoulli equation

Right heart catheterization (RHC) is the gold standard.

Question 8

What are the 4 functional classes of PAH?

Answer 8

I=no physical limitations
II=Feel symptoms in ordinary physical activities
III=feel symptoms in less than ordinary phys. activities
IV=Signs of RV damage, feel symptoms at rest.

Question 9

What recommendations are there in PAH concerning diuretics? Cardiac glycosides? Pregnancy?

Answer 9

 Diuretics
 symptomatic and clinical benefits in the treatment of
right heart failure
 In recent RCTs with new treatments, approximately
50% to 70% of patients were treated with diuretics

 Cardiac glycosides
 Digoxin incr. CO in IPAH
 Efficacy not known

Should be avoided, or termination recommended. Level of Evidence: Good; Net Benefit: Substantial; Grade of
recommendation: A.

We will need larger series before the general recommendation to avoid pregnancy in all patients with PAH is reconsidered

Question 10

When is anticoag recommended in PAH? Explain?

Answer 10

 Recommended in patients with
 Idiopathic PAH,
 Heritable PAH
 PAH due to anorexigens

 Explanation-
 In situ microscopic thrombosis
 RV failure  venous stasis  at increased risk for PE
 Improved survival with oral anticoagulation in IPAH

Question 11

When are calcium channel blockers recommended? Explain?

Answer 11

 IPAH

Useful in the following situations –

1. Absence of R heart failure
2. Demonstration of acute vasoreactivity

Explanation
 Smooth muscle hypertrophy
 Vasoconstriction

Contribute to the pathogenesis

Question 12

Should oxygen be given in PAH? Explain.

Answer 12

 Supplemental oxygen should be used as

necessary to maintain oxygen saturations

at > 90% at all times

 If hypoxemia is severe investigate for Right to Left shunt due to the reopening of a PFO

Explanation

Hypoxemia

 worsens pulmonary hypertension by vasoconstriction

 Contributes to the development and/or progression of PAH

Question 13

What medications target the NO pathway in treating PAH?

Answer 13

 Phosphodiesterase type 5 inhibitors (PDE5) inhibitors
Sildenafil -oral
 Tadalafil –oral
 Vardenafil- oral

 Soluble guanylate cyclase stimulators( sGC
stimulators)
 Riociguat – oral

Question 14

What medications target the PGI2 pathway in treating PAH?

Answer 14

 Prostacyclin Analogues

 Epoprostenol - IV

 Trepoprostinil – IV, subcutaneous, inhaled and oral

 Iloprost – inhaled

 Beraprost- oral . Approved in Japan.

Question 15

What medications target the endothelin pathway in treating PAH?

Answer 15

 Endothelin Receptor Antagonists

 Dual antagonists:
 Bosentan –oral
 Macitentan –oral

 Selective Antagonists
 Ambrisentan –oral

Question 16

When is lung transplantation recommended for PAH? How is it done?

Answer 16

 Lung Transplantation

 The advent of disease targeted therapy for severe PAH

has reduced and delayed patients referral for lung

transplant programs

 Important option for those who fail medical therapy

and remain in WHO-FC III or IV

SINGLE LUNG TRANSPLANTATION

Question 17

What is BAS? When should it be performed? What does it accomplish? How should it be performed?

Answer 17

 Balloon Atrial Septostomy (BAS)

 The creation of an interatrial right-to-left shunt can

decompress the right heart chambers, and increase left

ventricle pre-load and cardiac output

 BAS should be regarded as a palliative or bridging

procedure

 To be performed only by centers with experience in the

method

Question 18

What medication should be used in class IV? Class III? Aside from PAH, what can Riociguat be used to treat?

Answer 18

Epoprostenol

Class III-Any really.

Riociguat can also be used to treat Recurrent Pulm. thromboembolism pulmonary hypertension that can’t be treated by surgery.