PAH Flashcards
PAH
Progressive disease involving endothelial dysfunction–> elevated arterial pressure and pulmonary vascular disease
WHO Classification
Group 1: PAH
Causes: unknown, genetic, drug and toxin exposure, disease associated with PAH: CHD, HIV, connective tissue disorders
Treatment: meds specifically for PAH, CCB, Lung transplantation
PAH Epidemiology
Rare: 2-7.6 cases per million adults/year
Variable age at diagnosis: mean 50 +/- 14 years, 4 x more common in women
Underrecognized: median 1.1 years to diagnostic right heart catheterization, 1 in 5 symptomatic > 2 years before diagnosis
PAH Epidemiology Group 1
prognosis is poor but improving
approx 15% mortality within 1 year
median survival 6 years
negative predictors: poor exercise capacity, high right atrial pressure, right ventricular dysfunction, low cardiac output
Diagnosis
Echocardiogram
Right heart catheterization
Effects of PAH
Right side of heart has difficulty pumping against high pulmonary pressures
Leads to right heart ventricular failure
PAH disease progression
Vascular injury:
Endothelial dysfunction
Decrease NO synthase
Decrease prostacyclin production
Increase thromboxane production
Increase endothelin 1 production
Goals of therapy
alleviate symptoms
improve quality of life
prevent or delay disease progression
reduce hospitalization
improve survival
AVT
Acute vasoreactivity testing=positive responder=CCB
Acute vasoreactivity testing=negative responder, RV failure, or CCB contraindication= Do not use CCB
Acute vasoreactivity test
agents used include: inhaled NO, IV epoprostenol
positive test= drop in mPAP > 10 mmHg with PAP less than 40 mmHg with stable-improved cardiac output
WHO FC 1
Treatment naive PAH patients with WHO FC 1= continued monitoring for disease progression=determine when to start therapy
consider CCB if responder
monitor closely and consider initiation of worsening symptoms
WHO FC 2
Treatment naive PAH WITH WHO FC 2= Tolerate combo therapy?= Yes, ambrisentan + tadalafil
Cannot tolerate combo then ERA, RIOCIGUAT, PDE-5 INHIBITOR
WHO FC 3
Treatment naive PAH with WHO FC 3 W/O rapid disease progression or poor prognosis= Tolerate combo?= Ambrisentan + tadalafil
No: monotherapy= ERA, riociguat, or PDE-5 inhibtor
Nitric oxide pathway
PDE-5 inhibitors: sildenafil, tadalafil
Soluble guanylate cyclase stimulator: riociguat
Endothelin pathway
Endothelin Receptor Antagonists: bosentan, ambrisentan, macitentan
Prostacyclin Pathway
epoprostenol (IV)
iloprost (inhalation)
treprostinil (IV, SQ, inh, oral)
IP prostacyclin receptor agonist: selexipag
Phosphodiesterase Inhibitors
decreases conversion of cGMP to GMP
Increased levels of cGMP=pulmonary vasodilation
may used as monotherapy or in combo with other classes
considered first line in FC 2 OR 3 without rapid progression
Endothelin Receptor Antagonists
ET receptors on vascular smooth muscle mediate vasoconstriction
Overexpression f ET-1 in PH patients, correlates with remodeling
Blocking ET–> vasodilation
Options in class 2-4
Tadalafil + ambrisentan combo first line for class 2 and class 3 without rapid progression
Improve in 6MWD, pro-BNO, delay time to clinical worsening, optimize hemodynamics
ERA adverse events
peripheral edema
LFT abnormalities
Anemia
BBW: embryo-fetal toxicity
REMS: reproductive harm and hepatotoxicity (bosentan)
Clinical effects
improvement not likely seen for 8-10 weeks
hemodynamic parameters
exercise capacity
time to clinical worsening
Soluble guanylate cyclase stimulator
Riociguat
May be used as alternative to PDE-5i
cannot be used in combo with tadalafil or sildenafil due to risk of hypotension
improves exercise capacity, WHO FC, and time to clinical worsening
AMBITION
reason the guidelines changed
TRITON
triple therapy vs. dual therapy in naive PAH group 1 patients
triple therapy and dual therapy showed no difference
WHO FC 3 WITH RAPID PROGRESSION OR POOR PROGNOSIS or WHO FC 4
Candidate for parenteral prostanoids? Yes= SC treprostinil, IV treprostinil, IV epoprostenol
Not a candidate for parenteral= inhaled or oral prostanoid in combo with ERA + PDE-5i
Prostacyclins
inhibit platelet aggregation
Prostacyclin ADR
headache, jaw pain, limb pain, flushing/skin rash, diarrhea , N/V, thrombocytopenia
IV: line infections, erthemia
Treprostinil IV/SQ
IV infusion requires stable access, do not co-infuse with anything else
SQ is preferred as it avoids risk of central lines
Adjunct therapy
Anticoagulation may consider depending on cardiac function
warfarin: INR goal 1.5-2.5
ASA: 81 mg daily
