Pulmonary HTN Flashcards
What drug is known to cause hemorrhagic cystitis?
cyclophosphamide
How is hemorrhagic cystitis prevented with cyclophosphamide?
Mesna
When does pulmonary VENOUS HTN occur?
CHF. When the LV fails, stroke volume drops and extra volume and pressure leak back to the pulmonary veins from the left heart
What is PAP in PAH?
25+ mm Hg at rest (30+ in exercise)
What PCWP (right heart cath required) and LVEDP (left heart catheterization required) is seen in PAH?
less than 15 mm Hg IN BOTH (because there is no pulmonary venous HTN)
Rules out LV dysfunction
What is LVEDP is more than 15 mm Hg?
suggests LV failure because of original pulmonary venous HTN
What causes primary PAH (iPAH)?
Unknown (absence of a demonstrable cause)
What things can cause PAH (these cause 2ndary PAH)?
- parenchymal lung disease
- chronic thromboembolic disease
- LV valve disease
- myocardial disease
- any condition that promotes hypoxic vasoconstriction
There are five groups of PAH. What are groups 1-3?
1- PAH (iPAH, PortoPulm, Heritable, BMPR2, CT tissue)
2- PAH due to heart disease
3- PAH due to lung disease
What are groups 4-5?
4-CTEPH: Chr Thromboembolic Pulm HTN
5- PAH due to multifactorial etiology
When are plexiform lesions seen?
mostly in iPAH and familial PAH
What vascular factors are upregulated in PAH?
- Endothelin-1
- TXA-2
- VEGF (overexpressed in plexiform lesions)
- serotonin (constrictor)
What exogenous mediators promote vasoconstriction of the pulmonary artery?
- anorexiants
- cocaine
What vascular factors are downregulated in PAH?
- NO
- Prostacyclin
Which collagen vascular disease is most often associated with PAH?
Systemic sclerosis
What are some other pathologies associated with PAH?
- SLE
- MCTD
- RA
- HIV
- SCD
- Thrombocytosis
can get Raynaud’s phenomenon
What percentage of patients with portal HTN show PAH?
5%
Why would PAH been seen in hemoglobinopathies like SCD?
Free iron is released and iron scavenges NO and neutralizes it
MOI of Familial PAH
AD (incomplete penetrance)
What gene is messed up in familial PAH?
PPH1 on chromosome 2
What does defective PPH1 result in?
defective function of the bone morphogenetic protein receptors type II (BMPR2)
What do carriers of PPH1 show?
abnormal pulmonary vascular response to exercise
What are the effects of NO?
vasodilation and inhibition of smooth muscle growth (nearly absent in PAH)
Where is serotonin stored?
platelets mainly
What does serotonin promote?
pulmonary vasoconstriction and proliferation of smooth muscle cells
T or F. Plasma serotonin concentrations are higher than normal in PAH
T.
How is Ca2+ mediated constriction different in PAH?
voltage-gated K+ channels that normally control the release of calcium are defective and you see an INCREASE in intracellular calcium and thus more contraction
Mean age of PAH diagnosis
36
How does PAH present?
- fatigue
- exertional dyspnea, chest pain and syncope
- edema eventually due to RV failure
Signs of PAH?
- OUTWARD (not down and out) shift of the apical impulse
- dyspnea
- widely split S2
- parasternal heave
- palpable P2
When is a helical CT with contrast indicated?
to rule out pulmonary embolism
When are High resolution CT scan indicated?
to rule out interstitial disease
What is the best initial test for PAH?
Echocardiography (good screen)
In a RHC (right heart catheterization) report, the parameter that distinguishes PAH from PVH is what?
The PCWP
T or F. Vasoreactive patients have a relatively better prognosis compared to those with vasoreactivity
T. This confirms that CCBs are safe (the majority of patients are not vasoreactive)
During RHC, what is the best agent for vaso-reactivity testing?
NO (inhaled and see immediate acting and short duration)
Inhaled while the catheter is in place
What is a positive vasoreaction defined as?
20+% reduction in PAP and PVR with increased or unchanged cardiac output and minimally reduced or unchanged systemic blood pressure and SVR
Quantified requirements for a positive vasoreactive test
10+ mm Hg drop in MPAP
and MPAP should drop to less than 40mm Hg
What would an ECG show to indicate PAH?
shows evidence of RH enlargement, tricuspid insufficiency, and paradoxical motion of the IVS
How is tricuspid insufficiency calculated?
4V (velocity) ^2 + RA pressure
What are two diseases where PaO2 will decrease with walking/exercise early on?
- pulmonary fibrosis
- PAH
What patients are prime for sleep studies?
those with BMI 35+ and look at risk for sleep apnea
How to confirm PCWP is not high?
RH catheterization (this is the confirmatory test for PAH)
What are the typical PFT findings in PAH?
Normal FEV1, FVC, TLC and REDUCED DLCO
aka ‘pulmonary vascular disease pattern’
Which agent should be selected for a patient with PAH, who is SOB at rest (WHO class IV)?
Ipoprostenol (only available IV)
What pattern on an EKG is typical of PAH?
S1Q3T3
What is a PGI2 receptor agonist?
Selexipag (brand new)
What is a drug used to increase cGMP?
Riociguat
Adjuvant therapy for PAH?
oxygen (get hypoxemia at rest sometimes) and
anticoagulation in Group I patients (PPH)
Why are patients with PPH at an increased risk of intrapulmonary thrombosis or VTE?
sluggish pulmonary blood blood, dilated right heart chambers, venous stasis, and commonly sedentary lifestyles
What is the current anticoagulant drug of choice for PAH?
Warfarin (Goal: INR of 2)
How is the prognosis of PAH?
Variable depending on the severity of hemodynamic derangement an the response to vasodilator therapy
mean survival: 3 yrs
Which groups of PAH tend to live longer?
I and II
What are some ECG findings associated with poor outcome in PAH?
- large right atrium
- presence of pericardial effusion
- large degree of septal shift during diastole
Patients with PAH are at risk for both ____ and ____.
progressive right heart failure and sudden cardiac death.
CPR after CV collapse in PAH pts is generally unsuccessful
Is edema seen in PAH?
Yes (diuretics help) and JVD is seen
When to suspect PAH?
Suspect PAH in patients with insidious onset, gradually progressive shortness of breath without wheezing
What should be done if lung function continues to deteriorate in PAH?
refer for lung transplant
Best drugs for PAH?
Epoprostenol and Bosentan
Advantage of Macitentan?
less liver toxicity
