Pulmonary Arterial Hypertension

Aka: Pulmonary Arterial Hypertension, Primary Pulmonary Hypertension, Pulmonary Hypertensive Crisis, Idiopathic Pulmonary Arterial Hypertension, Familial Pulmonary Arterial Hypertension

1. See Also
   1. Pulmonary Arterial Hypertension Crisis
   2. Pulmonary Hypertension
   3. Pulmonary Hypertension Causes
   4. Pulmonary Hypertension Diagnosis
   5. Pulmonary Hypertension Management
2. Epidemiology
   1. Incidence: 1-2 cases per 1 million (rare)
   2. Female predominance after Puberty in ratio of 1.7 to 1
   3. Most prevalent in ages 20 to 40 years old
3. Causes
   1. See Pulmonary Arterial Hypertension Causes
   2. Idiopathic or familial
   3. Genetic associations
      1. BMPR2 gene
      2. ALK1 gene
      3. Endoglin (with or without Hereditary Hemorrhagic Telangiectasia)
4. Associated Conditions
   1. Collagen Vascular Disease (e.g.` Systemic Sclerosis)
   2. HIV Infection
   3. Includes Persistent Pulmonary Hypertension of the Newborn
   4. Predisposing medication use (see Pulmonary Arterial Hypertension Causes)
5. Pathophysiology
   1. Progressive narrowing of distal pulmonary arteries
   2. Processes
      1. Inflammation
      2. Hypercoagulability
      3. Pre-capillary pulmonary arteriole disorder
         1. Endothelial dysfunction
         2. Excess cell proliferation and dysfunctional apoptosis
         3. Vasconstriction
   3. Mediators
      1. Nitric oxide
      2. Prostacyclin
         1. Reduces platelet aggregation and causes vasodilation
         2. Reduced in PAH
      3. Cyclic guanosine monophosphate (cGMP)
         1. Vasodilator
         2. cGMP is rapidly degraded by PDE5 (Phosphodiesterase 5) which present in right ventricle of PAH patients
      4. Endothelin-1
         1. Vasoconstricor and smooth muscle mitogen
         2. Increased in PAH
   4. Pulmonary circulation obstruction results from underlying factors
      1. Increased pulmonary vascular resistance
         1. Contrast with the normal low-resistance, high compliance pulmonary circulation
      2. Right Ventricular Afterload
         1. Right ventricle gradually compensates for increasing right Ventricular Afterload increases
         2. Right ventricular increased pressure and volume force interventricular septum to bow into left ventricle
            1. Results in decreased left ventricular filling and ejection fraction
         3. Ultimately compensation fails, resulting in Right Ventricular Failure
         4. Right ventricle is unable to compensate for acute increases to Afterload resulting in PAH Crisis
6. Symptoms
   1. See Pulmonary Hypertension
   2. Dyspnea (60%)
   3. Fatigue (19%)
   4. Syncope or Presyncope (13%)
   5. Chest Pain
   6. Palpitations
7. Signs
   1. See Pulmonary Hypertension
   2. Signs of underlying cause (e.g. Portal Hypertension, Connective Tissue Disease)
   3. Signs of right ventricular Heart Failure
      1. Jugular Venous Distention
      2. Hepatomegaly
      3. Ascites
      4. Peripheral Edema
      5. Tricuspid regurgitation murmur
8. Diagnosis
   1. See Pulmonary Hypertension Diagnosis for labs, imaging and diagnostics
9. Management
   1. See Pulmonary Arterial Hypertension Management
10. Complications
    1. See Pulmonary Arterial Hypertension Crisis (PAH Crisis)
11. Prevention
    1. Avoid predisposing factors (e.g. weight loss drugs)
    2. Avoid pregnancy (mortality risk approaches 50% in some studies)
    3. Vaccinations
       1. Influenza Vaccine
       2. Pneumococcal Vaccine
    4. Advanced Directives: Severe Pulmonary Arterial Hypertension
       1. Advise Do-Not-Resuscitate (very poor outcomes for ROSC)
       2. Discuss end-of-life wishes
12. Prognosis
    1. Median survival from diagnosis
       1. Prior medications: 2.8 years
       2. New medications: may exceed 10 years
13. References
    1. Meter (2013) Crit Dec Emerg Med 27(5): 2-10
    2. Dunlap (2016) Am Fam Physician 94(6):463-9 [PubMed]
    3. Galie (2009) Eur Heart J 30(20): 2493-537 [PubMed]
    4. Simmonneau (2009) J Am Coll Cardiol 54(1 Suppl): S43-54 [PubMed]