Pulmonary Hypertension

1. See Also
   1. Pulmonary Arterial Hypertension
   2. Pulmonary Hypertension Causes
   3. Pulmonary Hypertension Diagnosis
   4. Pulmonary Hypertension Management
   5. Cor Pulmonale
2. Epidemiology
   1. Prevalence increases with age (Prevalence may approach 10-20%)
3. Definitions
   1. Pulmonary Hypertension
      1. Pulmonary artery systolic pressure >30 mmHg
      2. Pulmonary artery mean pressure >25 mmHg (by cardiac catheterization)
   2. Pulmonary Arterial Hypertension (Previously known as Primary Pulmonary Hypertension)
      1. Idiopathic Pulmonary Hypertension
   3. Secondary Pulmonary Hypertension
      1. Secondary to one of Pulmonary Hypertension Causes
   4. Cor Pulmonale
      1. Right Ventricular Failure
      2. Secondary to respiratory cause of Pulmonary Hypertension
4. Pathophysiology
   1. Pulmonary vascular bed pressures (25/10) are typically much lower than systemic pressures (120/80)
   2. Pulmonary vasculature changes in response to increased pressure
      1. Pulmonary artery medial hypertrophy
      2. Intimal fibrosis
      3. Fibrinoid necrosis
      4. Intravascular thrombus formation
5. Types: Acute Pulmonary Hypertension
   1. Acute increase in main pulmonary artery pressures
   2. May result from many acute insults (e.g. Hypoxia, hypercapnia, acidosis, left Heart Failure)
6. Types: Chronic Pulmonary Hypertension (replaces old system of primary versus secondary Pulmonary Hypertension)
   1. Pulmonary artery Hypertension (WHO Group 1, rare)
      1. Least common Pulmonary Hypertension type, but most specific management options
      2. Mechanism
         1. Progressive distal pulmonary artery narrowing
      3. Causes
         1. Idiopathic or familial
         2. Includes Persistent Pulmonary Hypertension of the Newborn
         3. Risk factors include Collagen vascular disease including Systemic Sclerosis, as well as HIV Infection
   2. Pulmonary Hypertension associated with left heart disease (WHO Group 2, most common)
      1. Mechanism
         1. Pulmonary venous congestion with Vasoconstriction and venous remodeling
      2. Causes
         1. Left-sided valvular heart disease
         2. Left-sided atrial or ventricular heart disease
         3. Left Heart Failure (>25% have Pulmonary Hypertension)
   3. Pulmonary Hypertension associated with lung disease, Hypoxemia or both (WHO Group 3, common)
      1. Mechanism
         1. Alveolar capillary bed destruction or chronic hypoxic Vasoconstriction
      2. Causes
         1. Chronic Obstructive Lung Disease
            1. Pulmonary Hypertension in 20% of hospitalized COPD and 50% of end-stage COPD
         2. Interstitial Lung Disease
         3. Sleep Apnea
         4. Chronic high altitude exposure
   4. Pulmonary Hypertension associated with chronic thromboembolic disease (WHO Group 4)
      1. Mechanism
         1. Vasoconstriction and pulmonary arterial bed remodeling in response to large vessel obstruction
      2. Causes
         1. Thromboembolism of proximal or distal pulmonary arteries (3.8% with PH at 2 years after PE)
         2. Thromboembolism not due to thrombi (e.g. tumor, Parasites)
   5. Miscellaneous Pulmonary Hypertension (WHO Group 5)
      1. Sarcoidosis
      2. Pulmonary vessel compression
7. Causes
   1. See Pulmonary Hypertension Causes
8. Associated Conditions
   1. Chronic Hemolytic Anemia
   2. Congenital Heart Disease
   3. Connective Tissue Disease
   4. Human Immunodeficiency Virus (HIV Infection)
   5. Portal Hypertension
   6. Persistent Pulmonary Hypertension of the Newborn
9. Symptoms
   1. Common
      1. Progressive Dyspnea on exertion (Exercise intolerance)
      2. Fatigue (or generalized weakness)
      3. Syncope (especially Syncope on exertion)
   2. Less Common
      1. Hoarseness (Oertner Syndrome)
         1. Pulmonary artery compress left recurrent laryngeal
      2. Angina-type exertional Chest Pain
   3. Rare
      1. Cough
      2. Hemoptysis
      3. Raynaud's Phenomenon (2%)
10. Signs
    1. Jugular Vein distention
    2. Prominent right ventricular impulse
    3. Fixed Split S2 Heart Sound
       1. Accentuated second pulmonic valve component (P2)
          1. Louder than the aortic second sound (A2)
       2. A2 remains louder as stethoscope moved to apex
    4. Right Ventricular Fourth Heart Sound (S4 Heart Sound)
    5. Right-sided Third Heart Sound (S3 Heart Sound)
       1. Indicates advanced disease
       2. Associated with poor prognosis
    6. Tricuspid insufficiency murmur
       1. More prominent as right ventricle dilates
    7. Hepatomegaly
    8. Peripheral Edema
11. Diagnosis
    1. Challenging diagnosis
       1. Diagnosis is often delayed 2-4 years after symptom onset
          1. Despite multiple primary care and specialist visits
       2. More significant cases may present with Right Heart Failure
          1. Lower Extremity Edema
          2. Jugular Venous Distention
    2. See Pulmonary Hypertension Diagnosis
    3. Mean Pulmonary Artery Pressure (PAP)
       1. Normal: <15 mmHg
       2. Pulmonary Hypertension
          1. Rest: 25 mmHg or higher
          2. Exercise: 30 mmHg or higher
    4. Pulmonary capillary wedge pressure (PCWP)
       1. PCWP <15 mmHg: Pre-capillary Pulmonary Hypertension
          1. All Causes of Pulmonary Hypertension
          2. EXCEPT those due to left heart disease (WHO Groups 1,3,4,5)
       2. PCWP >15 mmHg: Post-capillary Pulmonary Hypertension
          1. Left heart disease related causes (WHO Group 2 Pulmonary Hypertension)
12. Labs: Initial Dyspnea Evaluation
    1. Complete Blood Count (CBC)
       1. Evaluate for Anemia (high output Heart Failure)
    2. Comprehensive Metabolic Panel (Electrolytes, Renal Function tests, Liver Function Tests)
    3. B-Type Natriuretic Peptide (BNP)
    4. Serum Troponin
    5. Thyroid Stimulating Hormone (TSH)
       1. Evaluate for Hyperthyroidism (high output Heart Failure)
    6. Other tests to consider at initial presentation
       1. HIV Test
       2. Oximetry (6 Minute Walk Test)
13. Imaging
    1. Chest XRay
       1. Cardiomegaly
       2. Right atrial enlargement
       3. Mediastinal narrowing (lateral view)
          1. Right Ventricular Hypertrophy
          2. Pulmonary vasculature pruning (vessels taper off quickly at hilum)
14. Diagnostics
    1. See Pulmonary Hypertension Diagnosis
    2. Echocardiogram
       1. First-line testing for suspected cases
       2. Estimated pulmonary pressure >35 to 40 mmHg is consistent with Pulmonary Hypertension
       3. Also evaluates right ventricular function
       4. Right Ventricular Hypertrophy
          1. Right ventricular wall thickening (suspicious if >5mm, RVH if >10mm)
          2. Right ventricle pushes into left ventricle on PSAX View (D Sign)
    3. Electrocardiogram (EKG)
       1. See Right Ventricular Strain EKG Pattern
       2. Right Ventricular Hypertrophy
       3. Right Bundle Branch Block
       4. Right strain pattern (S1-Q3-T3 pattern)
       5. T Wave Inversion V1-V4
       6. ST Elevation in aVR
       7. Sinus Tachycardia
       8. Atrial Fibrillation
          1. New onset rate control may be challenging in Pulmonary Hypertension and risk decompensation
    4. Pulmonary Function Tests
       1. Evaluate for other Dyspnea Causes
    5. Evaluate WHO functional class status
       1. Six minute walk test (with oximetry)
15. Evaluation: Screening of high risk groups
    1. Protocol
       1. Annual Echocardiogram
       2. Reflex to right heart catheterization if positve Echocardiogram for pulmonary artery Hypertension
    2. Indications
       1. BMPR2 gene positive (screen first degree relatives for gene)
       2. HIV Infection
       3. Portal Hypertension (if considering liver Transplantation)
       4. Prior appetite suppressant medication such as Fenfluramine if symptoms
       5. Sickle Cell Disease
       6. Systemic Sclerosis
       7. Congenital Heart Disease with shunt
       8. Recent Acute Pulmonary Embolism with persistent symptoms at 3 months
          1. Consider ventilation-perfusion scan with reflex to Pulmonary Angiography if positive
16. Differential Diagnosis
    1. See Causes of Dyspnea with Clear Lung Sounds
17. Management
    1. See Pulmonary Hypertension Management
18. Complications
    1. Increased mortality
       1. Five year mortality: 36%
       2. In comorbid conditions (e.g. COPD), Pulmonary Hypertension is among greatest risks for increased mortality
    2. Right Ventricular Failure
       1. Common outcome of persistently increased pulmonary artery pressures regardless of cause
          1. Thin walled right ventricle responds poorly to high pressures and leads to Right Heart Failure
       2. Secondary to persistent Pulmonary Hypertension
       3. Cor Pulmonale: Subtype of Right Ventricular Failure
          1. Second to respiratory cause of Pulmonary Hypertension
19. Resources
    1. Pulmonary Hypertension Association
       1. https://www.phassociation.org/
20. References
    1. Orman, Greenwood and Swaminathan in Herbert (2016) EM:Rap 16(10): 9-11
    2. Dunlap (2016) Am Fam Physician 94(6):463-9 [PubMed]
    3. Gaine (2000) JAMA 284:3160-8 [PubMed]
    4. Greenwold (2015) Emerg Med Clin North Am 33(3): 623-43 +PMID:26226870 [PubMed]
    5. Nauser (2001) Am Fam Physician 63(9):1789-98 [PubMed]
    6. Rubin (1997) N Engl J Med 336:111-7 [PubMed]
    7. Rubin (1993) Chest 104:236-50 [PubMed]
    8. McLaughlin (2009) Circulation 119(16): 2250-94 [PubMed]
    9. Stringham (2010) Am Fam Physician 82(4): 370-7 [PubMed]