Pulmonary Hypertension

See Also

Epidemiology

Prevalence increases with age
1. Prevalence estimated at 10% in age >65 years

Definitions

Pulmonary Hypertension
1. Pulmonary artery systolic pressure >30 mmHg
2. Pulmonary artery mean pressure >20 mmHg at rest (by cardiac catheterization)
Pulmonary Arterial Hypertension (Previously known as Primary Pulmonary Hypertension)
1. Idiopathic Pulmonary Hypertension (rare, high mortality)
Secondary Pulmonary Hypertension
1. Secondary to one of Pulmonary Hypertension Causes
Cor Pulmonale
1. Right Ventricular Failure
2. Secondary to respiratory cause of Pulmonary Hypertension

Pathophysiology

Pulmonary vascular bed pressures (25/10) are typically much lower than systemic pressures (120/80)
1. Low pressures are adequate to perfuse thin walled gas exchange capillaries with little resistance
2. Thin-walled right ventricle has adequate output to perfuse a normal, low pressure system
Right-sided pressures increase with primary or secondary disease
1. See Pulmonary Hypertension Causes
2. Idiopathic Pulmonary Arterial Hypertension (PAH)
3. Secondary to cardiopulmonary disease, autoimmune or metabolic disorders or thromboembolic disease
Pulmonary vasculature changes in response to increased pressure
1. Pulmonary artery medial hypertrophy
2. Intimal fibrosis
3. Fibrinoid necrosis
4. Intravascular thrombus formation
Right Ventricular Strain results from increased pulmonary circuit pressures
1. Progressive Right Heart Failure develops

Types
Acute Pulmonary Hypertension

Acute increase in main pulmonary artery pressures
May result from many acute insults (e.g. Hypoxia, hypercapnia, acidosis, Left Heart Failure)

Types
Chronic Pulmonary Hypertension (replaces old system of primary versus secondary Pulmonary Hypertension)

Pulmonary artery Hypertension (WHO Group 1)
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
Pulmonary Hypertension associated with left heart disease (WHO Group 2)
1. Most common cause of Pulmonary Hypertension
2. Mechanism
  1. Increased left atrial pressures increases pulmonary pressures
  2. Pulmonary venous congestion with Vasoconstriction and venous remodeling
3. Causes
  1. Left-sided valvular heart disease
  2. Left-sided atrial or ventricular heart disease
  3. Left Heart Failure (Up to 72-83% have Pulmonary Hypertension)
Pulmonary Hypertension associated with lung disease, Hypoxemia or both (WHO Group 3)
1. Second most common cause of Pulmonary Hypertension (esp. COPD)
2. Mechanism
  1. Increased pulmonary vascular resistance
    1. Alveolar capillary bed destruction
    2. Vasoconstriction of pulmonary arterioles secondary to chronic Hypoxia
3. Causes
  1. Chronic Obstructive Lung Disease
    1. Pulmonary Hypertension is found in 5% of COPD patients
    2. 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
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)
Miscellaneous Pulmonary Hypertension (WHO Group 5)
1. See Pulmonary Hypertension Causes
2. Sarcoidosis
3. Pulmonary vessel compression

Causes

See Pulmonary Hypertension Causes

Associated Conditions

Chronic Hemolytic Anemia
Congenital Heart Disease
Connective Tissue Disease
Human Immunodeficiency Virus (HIV Infection)
Portal Hypertension
Persistent Pulmonary Hypertension of the Newborn
Sickle Cell Disease
Stimulant Abuse (Cocaine, Methamphetamine)
First degree relative with Pulmonary Hypertension (Family History)

Symptoms

Common
1. Progressive Dyspnea on mild exertion or Exercise intolerance (60%)
2. Fatigue or generalized weakness (19%)
3. Syncope or Presyncope, especially with exertion (13%)
Less Common
1. Hoarseness (Oertner Syndrome)
  1. Pulmonary artery compress left recurrent laryngeal
2. Angina-type exertional Chest Pain
Rare
1. Cough
2. Hemoptysis (advanced disease)
3. Raynaud's Phenomenon (2%)

Signs

Findings are primarily of developing Right-Sided Heart Failure
Heart sounds
1. Fixed Split S2 Heart Sound
  1. Accentuated second pulmonic valve component (P2)
    1. P2 is louder than the aortic second sound (A2)
  2. A2 remains louder as stethoscope moved to apex
2. Right atrial Fourth Heart Sound (S4 Heart Sound)
3. Right ventricular Third Heart Sound (S3 Heart Sound)
  1. Indicates advanced disease
  2. Associated with poor prognosis
Murmurs
1. Pulmonic ejection Systolic Murmur
2. Pulmonic early Diastolic Murmur (graham steel murmur)
  1. Diastolic decrescendo murmur
3. Tricuspid insufficiency pansystolic murmur
  1. More prominent as right ventricle dilates
Other findings
1. Jugular Vein distention
2. Prominent right ventricular impulse
3. Hepatomegaly
4. Peripheral Edema
5. Ascites
6. Weight gain
7. Prolonged Capillary Refill
8. Decreased Oxygen Saturation

Diagnosis

See Pulmonary Hypertension Diagnosis
Challenging diagnosis
1. Diagnosis is often delayed 2-4 years after symptom onset
  1. Despite multiple primary care and specialist visits
  2. Have a high index of suspicion in patients with comorbid Associated Conditions (see above)
2. More significant cases may present with Right Heart Failure
  1. Lower Extremity Edema
  2. Jugular Venous Distention
Mean Pulmonary Artery Pressure (PAP)
1. Normal: <15 mmHg
2. Pulmonary Hypertension
  1. Rest: 25 mmHg or higher
  2. Exercise: 30 mmHg or higher
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)

Labs
Initial Dyspnea Evaluation

Complete Blood Count (CBC)
1. Evaluate for Anemia (high output Heart Failure)
Comprehensive Metabolic Panel (Electrolytes, Renal Function tests, Liver Function Tests)
B-Type Natriuretic Peptide (BNP)
Serum Troponin
Thyroid Stimulating Hormone (TSH)
1. Evaluate for Hyperthyroidism (high output Heart Failure)
Other tests to consider at initial presentation
1. HIV Test
2. Oximetry (6 Minute Walk Test)

Imaging

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)
CT Chest
1. Consider CT Pulmonary Embolism
2. Consider High Resolution CT in suspected Restrictive Lung Disease

Diagnostics

See Pulmonary Hypertension Diagnosis
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
Echocardiogram
1. First-line testing for suspected cases
2. Refer patients for positive results (even when incidental on echo performed for other reasons)
3. Peak tricuspid regurgitation velocity >2.8 m/s
  1. High probability if associated with other suggestive echo findings, or peak velocity >3.4 m/s
4. Estimated pulmonary pressure >35 to 40 mmHg is consistent with Pulmonary Hypertension
5. Also evaluates right ventricular function
6. 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)
Pulmonary Function Tests
1. Evaluate for other Dyspnea Causes (COPD, Asthma or Restrictive Lung Disease)
Six minute walk test (with oximetry)
1. Evaluates WHO functional class status
2. Predicts mortality in all Pulmonary Hypertension types
Right Heart Catheterization
1. Indicated Pulmonary Hypertension classification
2. Further evaluation of Pulmonary Arterial Hypertension and chronic thromboembolic Pulmonary Hypertension
3. Optional when Pulmonary Hypertension has a clear cardiopulmonary cause (e.g. lung disease, left sided heart disease)
4. Measures pulmonary artery wedge pressure (left atrial pressure)
  1. Normal in precapillary pulmonary vascular bed causes (e.g. Pulmonary Arterial Hypertension)
  2. Wedge pressure is increased in postcapillary causes (e.g. left-sided Heart Failure)
5. Measures pulmonary vascular resistance (PVR)
  1. Calculate PVR as the difference between mean pulmonary artery pressure and left atrial pressure
  2. PVR is increased in Pulmonary Arterial Hypertension (normal in Heart Failure)

Evaluation
Screening of high risk groups

Protocol
1. Annual Echocardiogram
2. Reflex to right heart catheterization if positve Echocardiogram for pulmonary artery Hypertension
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

Differential Diagnosis

See Causes of Dyspnea with Clear Lung Sounds
Common Causes in the Differential of Dyspnea on Exertion
1. Congestive Heart Failure
2. Coronary Artery Disease
3. Valvular Heart Disease
4. Obstructive Lung Disease (COPD, Asthma)
5. Restrictive Lung Disease (e.g. Pulmonary Fibrosis)
6. Pulmonary Embolism
7. Anemia

Management

See Pulmonary Hypertension Management
Specific management for Pulmonary Arterial Hypertension (WHO 1) and chronic Thromboembolism (WHO 4)
1. Other Pulmonary Hypertension Management is directed at the underlying condition

Complications

Increased mortality
1. Five year mortality: 33 to 36%
2. Six minute walk test (with oximetry) functional status
  1. Predicts mortality across all Pulmonary Hypertension classes
  2. Gall (2017) J Heart Lung Transplant 36(9): 957-67 [PubMed]
3. Factors that increase mortality
  1. Higher mortality when Pulmonary Hypertension is secondary to lung disease
  2. Lower mortality in chronic thromboembolic Pulmonary Hypertension
  3. Delayed diagnosis >2 years increases mortality 11%
    1. Khou (2020) Respirology 25(8): 863-71 [PubMed]
4. In comorbid conditions (e.g. COPD), Pulmonary Hypertension is among greatest risks for increased mortality
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
Pregnancy-Related Complications
1. Maternal mortality 12%
2. Pregnancy loss 23%
3. jha (2020) Eur J Obstet Gynecol Reprod Biol 253: 108-16 [PubMed]

Resources

Pulmonary Hypertension Association
1. https://www.phassociation.org/

References

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