Pulmonary Hypertension Flashcards
What is pulmonary hypertension?
-Pulmonary hypertension is higher than normal blood pressure in the arteries that carry blood away from the heart into the lungs
What is the mean pulmonary artery pressure?
20 mmHg at rest
What is pulmonary arterial hypertension?
Progressive disease involving endothelial function that leads to elevated pulmonary arterial pressure and pulmonary vascular resistance
Causes of pulmonary arterial hypertension
-Genetic
-Drug and toxin exposure
-Disease associated with PAH: CHD, HIV, connective tissue disorders
Treatment for pulmonary arterial hypertension
-Medications specifically for treatment of PAH
-CCB in responders
-Lung transplantation
What is pulmonary arterial wedge pressure?
-Estimates left atrial pressure
-Normal = 4-12 mmHg
-Elevated numbers signal LV failure or mitral stenosis
How is pulmonary vascular resistance calculated?
-Using a formula based on mPAP and PAWP
Negative predictors of pulmonary arterial hypertension
-Advanced functional class
-Poor exercise capacity
-High right atrial pressure
-Right ventricular dysfunction
-Low cardiac output.
Signs and symptoms of pulmonary hypertension
-Shortness of breath
-Fatigue
-Chest pain
-Edema
-Fainting or light-headedness
-Palpitations
What can be used to diagnose pulmonary hypertension?
-Echocardiogram
-Right heart catheterization
-Exercise testing
-Biomarkers
What are the effects of PAH?
-The right side of the heart has difficulty pumping against high pulmonary pressures
-Leads to right ventricular failure
WHO functional class 1
-Symptom-free when physically active or resting
WHO functional class 2
-Slight limitation of physical activity - ordinary activity may cause symptoms
-Comfortable at rest
WHO functional class 3
-Marked limitation in physical activity - less than ordinary activity causes symptoms
-Comfortable at rest
WHO functional class 4
-Significant symptoms with activity
-Symptoms at rest
Goals of therapy for PAH
-Alleviate symptoms
-Improve quality of life
-Prevent or delay disease progression
-Reduce hospitalization
-Improve survival
Pharmacotherapy options for the treatment of PAH
-Calcium channel blockers
-Direct pulmonary vasodilator
-Phosphodiesterase 5 inhibitors
-Endothelin receptor antagonists
-Prostacyclins
-Soluble guanylate cyclase stimulator
When should an oral CCB be used to treat PAH?
After a positive test of acute vasoreactivity
How do you treat PAH patients who are treatment naive with FC 2?
-Combination therapy with tadalafil and ambrisentan
-Monotherapy with either bosentan, macitentan, ambrisentan, riociguat, sildenafil, or tadalafil
How do you treat PAH patients with FC 3 without evidence of rapid disease progression?
-Combination therapy with tadalafil and ambrisentan
-Monotherapy with either bosentan, macitentan, ambrisentan, riociguat, sildenafil, or tadalafil
How do you treat PAH patients with FC 3 with evidence of rapid disease progression?
-Continuous IV epoprostenol, IV treprostinil, or SC treprostinil
-If unable to manage parenteral treatment then give inhaled or oral prostanoid
How do you treat PAH patients with FC 4?
-Continuous IV epoprostenol, IV treprostinil, or SC treprostinil
-If unable to manage parenteral treatment then give inhaled prostanoid in combination with an oral PDE-5 inhibitor and an oral endothelin receptor antagonist
How do you treat PAH patients with FC 3 and 4 with inadequate response to maximal pharmacotherapy?
-Lung transplant
-If not a candidate for lung transplant then put on palliative care
Which drugs target the nitric oxide pathway?
-PDE-5 inhibitors: sildenafil, tadalafil
-Soluble guanylate cyclase stimulator: riociguat
Which drugs target the endothelin pathway?
Endothelin receptor antagonists: bosentan, ambrisentan, macitentan
Which drugs target the prostacyclin pathway?
-Prostacyclins: epoprostenol (IV), iloprost (inh), treprostanil (IV, SQ, inh, oral)
-IP prostacyclin receptor agonist: selexipag
What is the mechanism of action of PDE-5 inhibitors?
-Decreases conversion of cGMP to GMP
-Increased levels of cGMP leads to pulmonary vasodilation
What is the mechanism of action of endothelin receptor antagonists?
-Overexpression of ET-1 in PH patients, correlates with remodeling
-Blocking ET leads to vasodilation
What does the ETA receptor do?
-Located on pulmonary smooth muscle walls
-Promotes vasoconstriction, proliferation, and inflammation
What does the ETB receptor do?
-Receptors on endothelium: promotes vasodilation, stimulates nitric oxide and prostacyclin production
-Receptors on muscle cells of vascular walls: cause vasoconstriction and cell proliferation
Required monitoring for endothelin receptor antagonists
-Pregnancy test
-LFTs
-Hemoglobin
What do we want to see improvement in when treating someone who has pulmonary hypertension?
-Exercise capacity
-Functional capacity
-Hemodynamic parameters
-Time to clinical worsening
-WHO FC
Why can’t riociguat be used in combination with a PDE 5 inhibitor?
Increases risk of hypotension
Results of the AMBITION trial
-In the combination group, peripheral edema, headache, nasal congestion, dizziness, and anemia were more common than in either monotherapy group
-Rates of hypotension were similar
-Rate of discontinuation and serious ADRs were similar across all groups
Mechanism of action of prostacyclins
Induce vasodilation in all vascular beds, inhibits platelet aggregation, cytoprotective and antiproliferative effect
Adverse reactions to prostacyclins
-Headache
-Jaw pain
-Limb pain
-flushing/skin rash
-Diarrhea
-Nausea/vomiting
-thrombocytopenia
-hypotension
Is SC or IV preferred for prostacyclins
SC is preferred to avoid risks of central lines
Clinical pearls for epoprostenol
-Start in hospital, titrate to effect
-Requires permanent, stable IV access
-Incompatible with everything
-Inadvertent bolus can lead to CV collapse and death
-Used less often than treprostinil
Clinical pearls for treprostinil
-start in hospital and titrate up
-IV infusion requires stable access
-SQ/IV dosing is the same
Key information for PGI2 analogs
-Prostacyclin therapy requires significant education before initiation
-Expensive
-Patients should have their own pumps and supplies
-May need to call a specialty pharmacy
Pregnancy considerations for patients with PAH
Avoid pregnancy
