PAH Flashcards
5 groups PAH list-
1- Idiopathic PAH 2- Left heart disease 3. Pulmonary disease and sleep disordered breathing 4. Thromboembolic disease 5. Mixed aetiology
Tell more about group 1 PAH-
Idiopathic PAH- sporadic with no FH and no risk factors
Heritable -6% eg major assoc is BMPR2
Drugs and toxins- SSRIs!!!
CT disease espec scleroderma and SLE
HIV- related to duration of infection NOT CD4 count
Portal hypertension
Schistosomiasis
Chronic haemolytic anaemia
Congenital heart disease
Persistent pulm hypertension of the newborn
What’s in group 5?
Haem disorders eg splenectomy and MPD
Systemic- LAM, vasculitis, neurofibromatosis, sarcoid
Metabolic eg thyroid
CKD on dialysis
ECG findings in PAH?
RV strain pattern (ST dep/TWI in inferior leads and V1-4)
RAD
R atrial enlargement (2.5mm in inferior leads)
RVH (R/S >1 in V1,
Increase or decrease in: thromboxane nitric oxide prostacyclin endothelin
Thromboxane and endothelin increase
NO and prostacyclin decrease
What should initial therapy be?
Treat underlying cause
anti coagulate target INR 1.5-2 if group 1 or 4
supp oxygen if resting or exercise induced hypoxaemia
Pulmonary rehab
Pneumococal and flu vax
Avoid pregnancy and strenuous activity (supervised exercise training ok)
Assess need for diuretics for management of fluid overload
bosentan MOA
endothelin receptor antagonist- receptors A and B
endothelin blocking prevents vasoconstriction and proliferation
macitentan MOA
Also two side effects
endothelin receptor antagonist- A and B receptors
Causes nasopharyngitis and anaemia Improves SURVIVAL as well as functional class and 6MWT
ambrisentan MOA
endothelin receptor antagonist- receptor A only
teratogenic
sildenafil MOA
oral phosphodiesterase 5 inhib
tadalafil MOA
oral phosphodiesterase 5 inhin
riociguat
oral guanylate cyclase activator –>increases sensitivity of sGC to endogenous NO AND directly stimulates the NO receptor
Also benefit in class 4!
Epoprostenol MOA
PGI2 prostacyclin
Produces vasodilation and antiproliferation
THE ONLY THERAPY SHOWN TO PROLONG SURVIVAL
iloprost MOA
PGI2 prostacyclin analogue
teprostinil
PGI2 prostacyclin analogue
Who do you actually treat with advanced therapy in terms of WHO functional classification?
I- onserve
II, III-(meaning SOB on activity but not rest) endothelin receptor antagonist, oral phosphodiesterase 5 inhibitor, oral guanylate cyclase activator
IV- IV (means evidence of RHF and may have SOB at rest) epoprostenol over alternative agents- improves survival and exercise capacity
What are the poor prognostic factors in PAH?
underlying scleroderma Increase BNP Increase RA pressure RHF signs 6 min walk test poor high WHO status RV dysfunction Men Older people
usually if any of these then straight to parenteral therapy rather than trying phosphodiesterase 5 inhib or endothelin receptor antagonist first
What monitoring whilst on Bosentan?
LFT monthly
Need barrier contraception
Mechanism of action phosphodiesterase 5 inhibitors?
NO–>activate guanylate cyclase–>increase cyclic GMP production–>vasorelaxation.
Phosphodiesterase usually breaks down cGMP.
So inhibitors increase concentration of cGMP and cAMP
Indications for surgical intervention for MR-
LVEF under 60%
LVESP over 40 mmHg
SEVERE Pulmonary hypertension at rest (over 50) or during exercise (over 60)
New onset AF
How does BMPR work?
inhibits SM proliferation and induces apoptosis
If abnormal–>vascular remodelling
Only 1/4 patients develop
Mutations found in 75% of familial cases and 40% of sporadic
Where are the endothelin A and B receptors
On vascular smooth muscle –.vasoconstriction
ET-B also on endothelium–>NO release and vasodilation
levels correlate with disease activity and mortality
Which advanced therapy can you give for group 4?
Riociguat
Which ones are those where advanced therapies may be life threatening?
Class 2 PAH- those with increase PCWP
Which Ca ch bl do you avoid in vasoreactive patients?
Not verapamil- neg inotrope
use nifedipine or diltiazem
NO EVIDENCE IN CTD ASSOCIATED PULMONARY HYPERTENSION
Improves survival IF you are a responder.
When do you NOT use warfarin in PAH?
COPD
systemic sclerosis as there is increased risk of bleeding
Used in IPAH, familial, chronic thromboembolic
Prostacyclin/Epoprostenol MOA
- Potent IV vasodilator- increases intracellular cAMP
- Inhibits platelet aggregation
Improves exercise tolerance, survival and haemodynamics
Side effects of prostacyclin/epoprostenol
Jaw pain
Diarrhoea
Arthralgia
CVC related
What is the problem with treprostinil?
Painful subcut infusion
What’s the problem with inhaled illoprost?
Short half life so have to use 6-12 times a day
Improves QOL, dyspnoea, 6mwt but not yet evidence mortality
What is selexipag?
The only orally available selective prostacycline receptor agonist
Add on therapy- trials ongoing
What is the limiting factor with Bosentan use?
hepatotoxicity
What do you risk if you transplant one of these patients?
Higher incidence of bronchiolitis obliterans.
Scleroderma- what evidence for what agents?
If vasoractive positive- ca ch bl can achieve prolonged survival, sustained functional improvement, and haemodynamic improvement
Epoprostenol - improves haemodynamics, functional capacity, and survival
Trepostinil- improve haemodynamics, symptoms, exercise capacity, possibly survival
Bosentan-mproved symptoms, the six-minute walking distance, and the WHO functional class
Sildenafil- significant improvement in hemodynamics and six-minute walk distances
Riociguat- increase time to clinical worsening, increase 6mwt
Survival scleroderma PAH?
Worse than idiopathic but better than SSc-associated ILD-PH
