Vancouver IM LMR

Thanks Dr. Brunner for this excellent teaching on pulmonary hypertension!

For your reference:

2020 CCS/CTS Pulmonary Hypertension position statement

Key takeaways:

• Pulmonary hypertension defined by a mean pulmonary artery pressure of 20 mmHg or more (changed from previous guidelines)
• Sorting these patients into groups based on underlying etiology is important, as treatment varies for these groups (only Group 1 has specific therapeutic targets). You will need to know WHO classification:
  • Group 1 (Pulmonary arterial hypertension): Idiopathic PAH, heritable PAH, drug and toxin-induced PAH, vasodilator responsive PAH, associated PAH (connective tissue diseases, HIV, portal hypertension, congenital heart disease, others), pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)
    • Approximately half of this group are idiopathic, heritable or drug-induced.
  • Group 2: PH owing to left heart disease
  • Group 3: PH owing to lung disease and/or hypoxia (eg COPD – up to >50% in advanced COPD, ILD)
  • Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH) in 0.5-2% survivors of acute PE
  • Group 5: PH with unclear multifactorial mechanisms (sarcoidosis)
• Symptoms include fatigue (73%), dyspnea (60%), angina (47%), syncope (36%), leg/abdo swelling, abdominal pain, hoarseness (Ortner’s syndrome – compression of the recurrent laryngeal nerve)
• Diagnosis of PH:
  • Algorithm begins with an echocardiogram.
  • If intermediate to high probability by the guidelines criteria, assess for left heart disease (Group 2) and lung disease (Group 3) – suggested investigations include clinical assessment, ECG, PFT with DLCO, CXR, high resolution CT, ABG.
  • If a diagnosis of Group 2 or 3 pHTN cannot be made, proceed to VQ scan to assess for CTEPH. If CTEPH possible, proceed to CT pulmonary angiography and right heart cath. If CTEPH, Group 2 or 3 pHTN unlikely then these patients will need to be seen by the PH clinic and proceed to right heart cath for assessment of possible pulmonary arterial hypertension (Group 1).
• PAH treatment (group 1 only!)
  • Three classes of PAH treatments (group 1 only!):
    • Prostacyclin pathway: Epoprostenol (IV), treprostinil (sc), selexipag (oral prostanoid receptor agonist)
      • **Reminder: Risk of blood stream infection with parenteral routes
    • Nitric oxide pathway:
      • PDE5 inhibitors sildenafil, tadalafil, inhaled nitric oxide
      • Riociguat (sGC stimulator) – risk of hypotension and syncope
    • Endothelin-1 pathway: Bosentan, ambrisentan. Watch for liver enzyme elevation with bosentan (3x ULN in 10%), as well as leg edema/anemia (class effect)
  • Treatment algorithm for PAH (note: This will be done with PH specialist involvement)
    • Start with acute vasoreactivity test (?sensitive to CCB). If non-reactive begin therapy with multiple classes (eg tadalafil + bosentan/ambrisentan)
    • If in bad heart failure, may start with IV epoprostenol with combination oral therapy on top.
    • Treatment with combination therapy shown to be more effective than monotherapy in the AMBITION trial
    • If inadequate clinical response, max out combination therapy (eg triple therapy) and if still inadequate clinical response -> consider referral to lung transplantation.
  • Treatment aimed towards: Absence of right heart failure symptoms/signs, no progression, no syncope, good 6 minute walk distance over 440 m, NT-proBNP < 300/BNP < 50 ng/L, other hemodynamic/echo/cardiopulmonary exercise testing targets
• Other interesting points:
  • Group 4 PH (CTEPH) classically thought of as a venous disease with obstruction due to clot. However, it is actually a dual pulmonary vascular disorder with arterial involvement (similar path findings to PAH). High flow in the unoccluded pulmonary vasculature in CTEPH triggers arterial remodelling. Large proximal clots can be treated by pulmonary endarterectomy (offered in Toronto) and can result in resolution of PH in 50% of cases (big surgery – midline sternotomy, done under hypothermic circulatory arrest). Other options are lifelong anticoagulation for non-operable disease and consideration of riociguat.