Pulmonary Arterial Hypertension Flashcards
Pulmonary Hypertension (PH)
- higher than normal BP in the ___ that carry blood away from the heart into the ___
- mean pulmonary artery pressure (mPAP) greater than or equal to ___ mmHg at rest
- more common
- arteries
- lungs
- 20
Pulmonary Arterial Hypertension (PAH)
- progressive disease involving ___ dysfunction = elevated pulmonary arterial ___ and pulmonary vascular ___
- more rare
- endothelial
- pressure, resistance
PAH Causes
- unknown ( ___ )
- genetic
- ___ and ___ exposure
- disease associated with PAH: CHD, HIV, ___ tissue disorders
- idiopathic
- drug, toxin
- connective
PAH Treatment
- medications specifically for PAH
- ___ in responders
- ___ transplantation
- CCB
- lung
Hemodynamic Definitions
PH:
- mPAP > ___ mmHg
PAH:
- mPAP > ___ mmHg
- pulmonary artery wedge pressure (PAWP) < ___ mmHg
- pulmonary vascular resistance (PVR) > 2 ___
dont need to know
- 20
- 20
- 15
- wood units
Pulmonary arterial wedge pressure (PAWP) - estimates ___ atrial pressure
- normal = ___ - ___ mmHg
- elevated numbers signal ___ failure or ___ stenosis
Pulmonary vascular resistance (PVR)
- calculated using formula based on mPAP and PAWP
- left
- 4-12
- LV, mitral
PAH Epidemiology
rare
- mean age: 50 +/- ___ years
- 4x more common in ___
- median survial of ___ years
- prognosis is poor
Underrecognized
- median 1.1 years to diagnostic right heart catheterization
- 1/5 symptomatic > 2 years before diagnosis
- 14
- women
- 6
PAH Epidemiology
negative predictors
- advanced functional ___
- poor ___ capacity
- high ___ atrial pressure
- ___ ventricular dysfunction
- low ___
- class
- exercise
- right
- right
- CO
Signs and Symptoms
- ___ (27%)
- fainting or light headed (15%)
- ___ pain (22%)
- ___ (86%)
- palpitations
- __ (21%)
- fatigue
- chest
- SOB
- edema
Diagnosis
echocardiogram
- useful for evaluating potential ___ , RV function, estimating ___ and ___
right heart catheterization
- Confirms ___ and estimates ____
- assess response to pulmonary ___ before starting therapy (AVT)
exercise testing
- distance walked in 6 min
biomarkers
- ___ and NTproBNP
- causes, PAP, PVR
- diagnosis, severity
- vasodilators
- BNP
BNP = brain natriuretic peptide
Effects of PAH
- ____ side of heart has difficulty pumping against high ___ pressures
- leads to ___ ventricular failure
- right, pulmonary
- right
PAH Disease Progression
- risk factors and associated conditions
vascular injury (endothelial dysfunction)
- ___ nitric oxide synthase
- ___ prostacyclin production
- ___ thromboxane production
- ___ endothelin 1 production
disease progression
decreased
decreased
increased
increased
WHO Functional Classes
Class I
- symptom ___ when physically active or resting
Class II
- slight ___ of physical activity
- ordinary activity may cause ___
- ___ at rest
Class III
- marked ___ in physical activity
- less than ___ activity causes symptoms
- ___ at rest
Class IV
- significant symptoms with __
- symptoms at ___
- free
- limitation
- symptoms
- comfortable
- limitation
- ordinary
- comfortable
- activity
- rest
Treatment of PAH - PCOL
- CCB
- direct pulmonary vasodilators ( ___ )
- ___ inhibitors
- ___ receptor antagonists
- prostacyclins
- ___ guanylate cyclase stimulator ( ___ )
- iNO
- PDE-5
- endothelin
- soluble, riociguat
CHEST Guidelines
after diagnosis with right heart catheter
1) acute ___ testing (AVT)
2) if they respond positive, they get a ___
3) if negative, have RV failure, or CCB contrainidcation, do NOT do ___
vasoreactivity
CCB
CCB
Acute Vasoreactivity Test (AVT)
- done in cath lab during initial hemodynamic evaluation
- acute response to ___ -specific vasodilators predicts response to ___
- agents include (inhaled ___ , IV ___ )
- positive test = drop in mPAP > ___ mmHg with PAP less than ___ mmHg with stable improved ___
- pulmonary, CCBs
- NO, epoprostenol
- 10, 40, CO
CCBs
- only 5-8% of patients are responders; long term response is rare
- consider CCBs in positive responders without ___ sided failure
- do not use without ___ AVT
Recommended drugs
- long acting ___ 120-240 mg daily
- long acting ___ 240-720 mg daily
- ___ 20 mg daily
NO ___ due to negative inotropic effects
if pts do not improve to functional class ___ or ___ after CCB initiation, start additional or alternative PAH therapy
- right
- positive
- nifedipine
- diltiazem
- amlodipine
- verapamil
- I, II
WHO FC I
treatment naive PAH with WHO FC I
- continue monitoring for disease progression (dyspnea on exertion, fatigue, weakness)
- do not necesarily require immediate drug therapy; consider ___ if responder
CCB
WHO FC II
treatment naive PAH WHO FC II
Tolerate combo therapy?
- yes: combo treatment - ___ + ___
- no: monotherapy - ___ , ___ , or ___
- ambrisentan, tadalafil
- ERA, riociguat, PDE-5i
WHO FC III
Treatment naive PAH WHO FC III without rapid progression/poor prognosis
Tolerate combo?
- yes: combo therapy - ___ + ___
- no: monotherapy - ___ , ___ , or ___
ambrisentan, tadalafil
PDE-5i
- decreases conversion of ___ to GMP
- increased levels of ___ lead to ___ vasodilation
- sildenafil and tadalafil: improved ___ functional capacity
- may be used as ___ or in combination with other classes
- considered ___ in many cases (. FC ____ , FC ___ without rapid progression)
- cGMP
- cGMP, pulmonary
- 6MWD
- monotherapy
- first line, II, III
Endothelin Receptor Antagonists
ET receptors on vascular smooth muscle mediate ___
- overexpression of ET-1 in PH pts correlated with ___
- blocking ET = ___
Option in classes ___ - ___
- tadalafil + ___ combo is firstline for class ____ and ___ without rapid progression
improve ___, pro- ___, delay time to clinical worsening, and optimize ___
- vasoconstriction
- remodeling
- vasodilation
- II-IV
- ambrisentan
- II, III
- 6MWD, BNP, hemodynamics
AMBITION
- subjects were treatment naive patients with FC II or III
- tested combo therapy of ___ and ___ vs these drugs by themselves with placebo
TAKEAWAY:
- combo therapy more effective than mono
- however SE were more common ( rates of ___ were similar)
- ambrisentan, tadalafil
- hypotension
Prostacyclins
- prostacyclins stimulate the ___ pathway to increase pulmonary ___ , inhibit ___ aggregation, have cytoprotective and ___ effect
- parenteral prostacyclins = standard for severe PH with RV failure
- subQ ___ is becoming most common
- cAMP, vasodilation, platelet, antiproliferative
- treprostinil
