Pulmonary Arterial HTN Flashcards

1
Q

Normal hear anatomy

A
  1. superior vena cava
  2. inferior vena cava
  3. right atrium
  4. Tricuspid valve
  5. Right ventricle
  6. Pulmonary valve
  7. Pulmonary arteries

oxygen rich

  1. Pulmonary veins
  2. Left atrium
  3. Mitral valve
  4. Left ventricle
  5. Aortic valve
  6. Aorta
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2
Q

Pulmonary Arterial HTN (PAH) patho

A

-pulmonary arterioles narrow
-RV dilates
-pulmonary edema and damage
-thrombo and/or plexiform lesion formation

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3
Q

Pulmonary HTN (PH)

A

-higher than normal BP in arteries going from heart to lung
-mean artery pressure (MPAP) > 20mmHg at rest
-more common than PAH

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4
Q

Pulmonary Arterial HTN (PAH)

A

-progressive
-endothelial dysfunction
-elevated pulmonary arterial pressure and pulmonary vascular resistance
-rare

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5
Q

PH classifications

A
  1. PAH
  2. Left Heart Disease
  3. Lung Disease
  4. Chronic Thromboembolic PH
  5. PH from unclear mechanisms
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6
Q

Group 1: PAH causes

A

-unknown causes
-genetic/drug/toxin
-CHD, HIV, connective tissue disorders

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7
Q

Group 1: PAH tx

A

-meds fro PAH
-CCB in responders
-lung transplant

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8
Q

PAH (Grp1) Epidemiology

A

-rare
-2-7mil a year
-mean age 50 +/- 14
-underrecognized (1.1 years to heart catheter)
-1/5 asx > 2 years to diagnosis

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9
Q

PAH prognosis

A

-poor but improving
-15% mortality in 1 year
-median survival 6 years
-negative predictors: advanced functional class, poor exercise capacity, hight right atrial pressure, right ventricular dysfinction, low CO

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10
Q

Early PAH sx

A

-nonspecific = large differential diagnosis
-dizziness
-SOB
-palpitations
-fatigue
-edema

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11
Q

Late sx of PAH

A

-signs of right-sided HF
-syncope
-jugular venous distension
-SOB
-chest pain
-hepatomegaly
-swollen abdomen
-low BP

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12
Q

Diagnosis

A

-echocardiogram: eval RV function, PAP, and PVR
-Right Heart Catheterization: confirms dx, estimates severity, assess response to pulmonary vasodilators before starting therapy (AVT)
-exercise testing: distance walked in 6 min
-biomarkers: BNP and NTproBNP

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13
Q

Diagnositic imaging/procedure

A

-slide12

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14
Q

PAH labs

A

-mPAP > 20mmHg (mean pulmonary artery pressure)
-PAWP =/< 15mmHg (pulmonary artery wedge pressure)
-PVR > 2 wood units (pulm vasc resistance)

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15
Q

Pulmonary arterial wedge pressure (PAWP)

A

-estimates left atrial pressure
-normal 4-12
-PAH: 15mmHg
-elevated numbers = LV failure or mitral stenosis

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16
Q

Pulmonary vascular resistance (PVR)

A

-calc using mPAP and PAWP
-PAH: >2 wood units

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17
Q

WHO functional classifications

A

I: no limits
II: slight limit
III: marked limit
IV: inability to be active wo sx

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18
Q

Risk

A
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19
Q
A
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19
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20
Q
A
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20
Q

Pharma options for PAH

A

-CCB (if vasoreactive +)
-PDE-5 inhibitors
-sGC
-ERAs
-Prostacyclins
-Direct pulmonary vasodilator (inpatient only)

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21
Q

Vasoreactivity test

A

-done in cath lab during initial hemodynamic eval
-acute response to pulmonary-specific vasodilators predicts response to CCBs
-use inhaled NO or epoprostenol

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22
Q

Positive Vasoreactivity test

A

=drop in mPAP>10 w PAP less than 40 w stable-improved CO
-can initiate CCB

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23
CCB for PAH
-inc in calcium causes vasoconstriction and stimulates proliferation, migration, vascular remodeling -only 5% of pt respond -continually assess w vasoreactive test -goal: improve to FCI or II
24
which CCBs to use
-nifedipine 120-240mg -diltiazem 240-720mg -amlodipine 20mg -NO verapamil bc negative inotropic events
25
PAH tx that effects NO pathway
-PDE-5 inhibitors -sGCs
26
PDE-5 inhibitors mech
-dec conversion of cGMP to GMP -inc levels of cGMP = vasodilation -can be monotherapy but often combo
27
PDE-5 inhibitor drugs for PAH
-sildenafil 20mg -tadalafil 40mg -improved 6MWD, functional capacity -hearing/vision loss -hypotension -AVOID CYP3a4 subdtrates
28
Soluble Guanylate Cyclase Stimulator (sGC)
-riociguat -may use as ALT to PDE-5 (do NOT combo = hypotension) -antiproliferating and antiremodeling -improves exercise capacity, FC, and time to worsening
29
Endothelin receptor antagonist drugs
-Bosentan (mixed) -Ambrisentan (ETA) -Macitentan (ETA and ETB) -selectivity purpose unclear
30
ETA receptors
-located on pulmonary smooth muscle walls -promotes vasoconstriction, proliferation, and inflammation -targeted by bosentan and ambrisentan and macitentan
31
ETB receptors on endothelium
-vasodilation -stimulate NO and prostacyclin production
32
ETB receptors on muscle cells of vascular walls
-vasoconstriction -cell proliferation -upregulated expression in vasoconstriction
33
ERAs improve
-exercise capacity (6MWD) -FC -hemodynamic parameters -time to clinical worsening -WHO FC -improvement seen around 8-10 weeks
34
ERA STUFF
-
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Prostacyclin pathway
-prostacyclin stimulates cAMP to increase pulmonary vasodilation -parenteral prostacyclins are standard for severe PH w RV failure
43
Prostacylin drugs
-epoprostenol (IV) -Treprostinil (IV, inhaled, PO, SubQ) -selexipag (prostacyclin IP receptor agonist)
44
Prostacyclin overview
-oral for low risk class III -IV firstlin if class IV or rapidly progressing class III -improve sx, 6, hemodynamics (mortality in epoprostenol)) -can combo with ERA and PDE-5 or riociguat -NO oral, inhaled and parenteral concurrently
45
Prostacyclin mech
-induce vasodilation in all vascular beds -inhibits platelet aggregation -cytoprotective -antiproliferative effect
46
Prostacyclin ADRs
-thrombocytopenia (worse in epoprostenol) -hypotension -HA, pain, diarrhea
47
Oral prostacyclins
-option for pt who cannot use parenteral therapy -Treprostinil -Selexipag
48
Inhaled prostacyclins
-option for pt who cannot use parenteral therapy -Treprostinil (Tyvaso)
49
Tyvaso
-charged/plugged in -assemble device qd -2-3 min tx throughout the way
50
Tyvaso DPI
-no charging needed -simpler assembly -single inhalation per cartridge
51
52
Treprostinil IV/SubQ (REmodulin)
-4 hour halflife -always dose by weight at beginning -start 1-3ng/kg/min and titrate q8-12h to 10-20ng/kg/min then weekly at home by 2ng/kg/min increments up to goal (~50-80)
53
Treprostinil IV vs SQ
-IV if SQ not tolerated -SQ avoids risk of central lines (infection) -SQ more site reactions (tx w antihistamines) -SQ undiluted, IV needs diluent -SQ pumps small e and more portable
54
Prostacyclin: Epoprostenol IV
-Flolan (needs to be on ice) -Veletri (stable 48h) -3-5min t1/2 -must ALWAYS have backup cassette prepeared -abrupt d/c might precipitate PH crisis -DO NOT COADMIN W ANY OTHER FLUIDS
55
Prostacyclin med errors
-flushing of line -calc error -programming error -pump turned off -inappropriate change in weight
56
AMBITION trial
-ERA + PDE5i as initial therapy for pt WHO class II or III
57
PAH treatment guidelines
-PDE5i + ERA (low/mid risk) -add iv/sc PCA (high risk) -PDE5i OR ERA (comorbidities) -add PRA or switch PDE5i to sGC if above is not working
58
PAH CV comorbidities
-obesity -HTN -DM -CAD -lung disease
59
Sotatercept-csrk (Winrevair)
-new -activin inhibitor -mAb trap for TGF-B -restores balance between growth promoting and growth inhibiting pathways -SQq24days (reconstitiute) -avg peak onset 7 days w t1/2 24 days
60
Sotatercept-csrk (Winrevair) use
-adults w PAH to: -inc exercise capacity -inc functional class -dec risk of clinical worsening events
61
Sotatercept-csrk adverse effects
-erthrocytosis -thrombocytopenia -hemorrhage -HA, epistaxis, inj site -embryo-fetal harm -impaired fertility -AVOID in breastfeeding
62
PAH considerations
-maybe diuretics, O2, CV drugs -IV iron -flu and pneumonia vax
63
PAH tx in pregnancy
-use CCBs, PDE5, and prostacyclins -AVOID ERAs, riociguat, selexipag -us contraception
64
PAH and traveling
-supp O2 at sea level or high alt -travel w info abt disease and meds
65
Disease progression guidelines
-add ERA -add inhaled prostacyclin -consider lung transplant