Lecture 19: Pulmonary Hypertension Flashcards
Ppa equation
(CO x PVR) + Pla (Pla = pressure of LA)
Psa equation
(CO x SVR) + Pra (Pra = pressure of RA)
What is the definition of pulmonary hypertension
Ppa great than 25 mm Hg
Three causes of pulmonary hypertension
Increased CO, increased Pla, increased PVR
Three reasons for increased PVR
Destruction of pulmonary vascular bed (ILD, emphysema, PE), hypoxic vasoconstriction (COPD, high altitude), small pulmonary artery/arteriole vasculopathy (PAH)
What is PAH? Describe/define
Pulmonary arteriole hypertension –> fibrotic/proliferative lesions in muscular arteries
Progression of PAH histologically (4)
Medial hypertrophy –> intimal thickening –> in situ thrombosis and plexiform lesion
Pathogenesis of PAH (3 pathways)
Upregulated endothelin pathway; downregulated NO pathway, decreased prostacyclin pathway
Four causes of PAH
- Idiopathic (~50%); 2. Heritable (BMPR2 mutation w/ 20% penetrance); 3. Drug and toxin induced; 4. Associated PAH (~50%)
Five Associated PAH diseases
Connective tissue disorders (~50%), congenital heart disease (high pressure/flow –> endothelial dysfunction), portal hypertension, HIV, schisotomiasis
Is PAH common?
Nope! 5-15 cases per 1 million
Median survival of untreated PAH
2.8 years
What happens to the RV if you “clamp” the pulmonary artery? What does this mean?
It fails quickly (decrease in SV) –> cannot handle increases in pressure
Does the RV have isovolmic contraction/relaxation? How can we create this?
No (more efficient: ejects blood while contraction and fills while relaxing); pulmonic stenosis makes RV behave like LV
Three consequences of increased RV afterload and their consequences. Ultimate consequence?
Increased RV wall stress (–> RV ischema); decreased RV output (–> decrased LV output); increased RV dilation (increased leftward septal shift and regurge); cardiogenic shock
Symptoms of PAH (2 main classes)
Low perfusion: dyspnea, fatigue, chest pain, palpitations, lightheadedness, syncope; Congestion: abdominal pain and fullness, peripheral edema
Physical exam of PAH (5), including heart findings (6)
Hypoxemia, tachycardia, hypotension, JVD, symptoms of RV failure; Heart findings: RV heave, split S2, systolic TR murmur, diastolic PR murmur, RV S3, RV S4
What is a RV heave a sign of?
RV dilatation
A split S2 will have a loud A2 or P2 in PAH
P2
Is PAH associated with pulmonary edema? Why?
NO: no significant rales because resistance is PRIOR to capillaries in pulmonary vasculature, so capillary pressures are low
ECG in PAH (3)
RV hypertrophy/strain, incomplete/complete right bundle branch block, right atrial enlargement
What procedure can confirm the presence of pulmonary hypertension?
Right heart catheterization
If you wedge pressure is high (greater than 15 mm Hg), what is this consistent with?
Left sided disease
If you wedge pressure is low (less than 15 mm Hg), what is this consistent with?
Precapillary disease
Natural history of pulmonary hypertension
Over time with elevated pulmonary pressure, CO begins to drop because of RV heart failure; PVR will continue to rise and CO continues to fall (low perfusion sx); overtime, Pap will fall but Rap will rise (congestion sx)
Tx for PAH (5 meds/classes)
Ca2+ channel blockers; prostanoids; endothelial receptor antagonists; PDE-5 inhibitors; riociguat
When are Ca2+ channel blockers helpful for PAH? % patients?
If positive vasoreactivity test = able to vasodilate w/ administered vasodilator because this suggests a MUSCULAR problem; 13%
Prostanoids: mechanism and drugs
Stimulates adenylate cyclase –> increased cAMP –> vasodilation, antiproliferation, platelet aggregation inhibition; epoprostenol (IV), treprostinil (SC, IV, PO inhalation), iloprost (inhalation)
What is the only PAH medication with a proven survival benefit? What’s an important note about this medication?
Epoprostenol; require continuous IV administration
Effects of prostanoids
Improve hemodynamics, functional capacity and survival
Which has the longer half life, epoprostenol or trepostinil?
Trepostinil
Endothelin receptor antagonists: mechanism
Activation of ETA and ETB receptors –> sustained vasoconstriction and proliferation of vascular smooth muscle cells; ETB receptors also mediate pulmonary ET clearance and induce endothelial cell production of local mediators of vascular tone (NO, prostacyclin); SO you want to block A not B
Endothelin receptor antagonists: medicatons
Bosentan (PO), ambrisentan (PO), macitentan (PO)
Phosphodiesterase-5 inhibitors: mechanism
Inhibition of cGMP-specific phosphodiesterase;
vasodilation, antiproliferation, platelet aggregation inhibition –> improve hemodynamics and functional capacity
PDE-5: medications (2)
Sildenafil (PO, IV), tadalafil (PO)
Riociguat: mechanism
Stimulates soluble guanylate cyclase (sGC) –> sGC converts GTP to cGMP; vasodilation, antiproliferation, platelet aggregation inhibition –> improves hemodynamics and functional capacity
Cautions for use of pulmonary vasodilators
Decrease SVR –> system hypotension; abrupt medication withdrawal –> rebound pulmonary hypertension; worsen V/Q matching –> hypoxemia; increase pulmonary capillary pressure –> pulmonary edema
Why do you get worse V/Q matching with pulmonary vasodilators? Who is this important for? What is a fix?
Pulmonary vasodilator will dilate areas of the lung that might be poorly ventilated; those with lung disease; give medication via inhalation
Who do you avoid pulmonary vasodilators with? Why?
Those with elevated left atrial pressures; at risk for pulmonary edema because if you decrease the pre-capillary constriction, you increase the pressure in the avleoli which cannot be tolerated by the high pressure LA
SEs of pulmonary vasodilators
Vasodilation: headache, dizziness, flushing, nasal congestion; ERAs: teratogenic, peripheral edema, anemia; bosentan: liver toxicity; prostanoids: jaw pain, delivery system problems (subcutaneous and intravenous)
PAH: general treatment measures (4)
Supplemental O2, anticoagulation, digoxin (improved contractility), cardiopulmonary rehab (improve fxnl capacity)
PAH: surgical therapies (3)
Atrial septostomy (unloads RV, but hypoexmia results); pulmonary thromboendarectomy (patients with CTEPH); lung transplant
Pulmonary HTN: WHO Classificiations
1: PAH; 2: Left heart; 3: Lung disease; 4: Chronic thromboembolic pulmonary HTN; 5: Misc
