Pulmonary Hypertension

Snapshot

A 37-year-old woman is referred to the pulmonologist’s office from her PCP for worsening shortness of breath. She reports that she has had increasing dyspnea on exertion and fatigue for the past 3 years, but it has gotten much worse in the last 2 months. She used to walk around the neighborhood with her friends but now gets short of breath with occasional chest pain just walking around the house. Her past medical history is otherwise completely negative. On physical exam, she has a JVP of 13 cm H
2O, a loud P2, an S3, a right-sided heave, a liver palpable 3 cm below the costal margin, and bilateral leg edema. She is sent for a trans-thoracic echocardiogram which estimates a high pulmonary artery systolic pressure and shows right ventricular hypertrophy and right heart failure. The diagnosis is confirmed with a right heart catheterization and she is started on epoprostenol.

Introduction

Clinical definition
- mean pulmonary artery pressure ≥ 20 mmHg
  - normal = 8-20 mmHg
  - gold standard for measurement is right heart catheterization
Epidemiology
- incidence
  - varies by etiology; affects all ages, races, and genders
  - can be very rare (~4 cases per million for idiopathic pulmonary hypertension (IPAH))
  - or relatively common 10-40% of patients with at-risk associated diseases (below)
- demographics
  - females > males
    - up to 9:1 (for IPAH)
Etiologies

Etiologies of Pulmonary Hypertension
Primary Etiologies
Etiology	Key Points
Idiopathic pulmonary arterial hypertension (IPAH)	By definition, the cause is unknown
Hereditary pulmonary arterial hypertension (HPAH)	Mutation in the BMPR-2 geneacts normally to inhibit smooth muscle growth Mnemonic: Blocker of Muscle PRoliferationMore common in women (9:1)Poor prognosis
Secondary Etiologies
Etiology (secondary to)	Key Points
Autoimmune disease	Systemic sclerosis > SLE >> RAInflammation of vessel wall leads to scarring and stiff vessels
Drugs	Direct pulmonary vasoconstrictione.g., cocaine or methamphetamine
Infection	Schistosomiasisleading cause of pulmonary hypertension in endemic areasHIV
Left-to-right shunt	Increased flow to pulmonary systeme.g., from congenital heart defects
Left heart disease	Decreased cardiac output backs blood into pulmonary circuite.g., left heart failure or mitral valvular disease
Lung disease/hypoxia	Decreased oxygen delivery leads to hypoxemic pulmonary vasoconstrictione.g., COPD, obstructive sleep apnea, obesity hypoventilation syndrome, or high altitudes
Thromboembolic disease	Chronic, recurrent micro-emboli decrease the cross-sectional area of pulmonary vessels
Unclear/miscellaneous	e.g., carcinoid syndrome, sarcoidosis, vasculitis, or metabolic disorders

Pathogenesis
- common final pathway for all etiologies
  - luminal injury from increased pulmonary pressure
  - smooth muscle proliferation of the media and intima
  - fibrosis resulting in plexiform lesions on pathology
- fibrosis leads to stiff vessels
- increased pulmonary vascular resistance (PVR)
- right ventricle has to pump harder to overcome resistance
- right ventricular hypertrophy
- right heart failure
Associated conditions
- schistosomiasis
- systemic sclerosis
- SLE
- HIV
- persistent pulmonary hypertension of the newborn
Prognosis
- progressive and fatal if untreated
- incurable
  - treatment focuses on slowing the disease progression
- rate of progression is variable
for IPAH and HPAH, 5-year survival is approximately 50%

Presentation

Imaging

Studies

Labs
- BNP
  - non-specific
Diagnostic procedures
- right heart catheterization
  - allows measurement of pulmonary arterial pressures
  - gold standard for diagnosis
Diagnosis
- clinical diagnosis by appropriate history, physical exam, and imaging/lab findings
- very likely if echocardiogram estimates high pressures
if few or ambiguous clinical findings, may need to confirm with right heart cath (early IPAH and HPAH)

Differential

Congestive heart failure (without PH)
- clinically very similar
- distinguishing factors
  - typically, a long history of heart attacks, coronary artery disease, hypertension, and/or other risk factors for heart failure
  - can be distinguished by echo and/or cath
Coronary artery disease
- can also present with exertional chest pain, shortness of breath, and fatigue
- distinguishing factors
  - positive stress testing
  - coronary vessel occlusion and normal pulmonary pressures upon catheterization
Liver disease
- can present with lower extremity swelling and RUQ pain
- distinguishing factors
  - lack of respiratory symptoms
normal JVP

Treatment

Management approach
- as PH is incurable, management is focused on slowing disease progression and alleviating symptoms
- for PH secondary to other disease (heart, lung, etc…), treat the underlying cause
Medical
- for symptoms
  - oxygen
  - diuretics
  - exercise therapy
- PH-specific therapies
  - prostacyclin (PGI₂)
    - epoprostenol (IV) and iloprost (inhaled)
    - mechanism
      - vasodilation
    - side effects
      - jaw pain and flushing
  - endothelin receptor antagonists (bosentan)
    - endothelin-1 (ET-1) is a potent vasoconstrictor in the lungs
    - mechanism
      - blocks the ET-1 receptor to decrease vasoconstriction
    - side effects
      - hepatotoxic
  - PDE-5 inhibitors (sildenafil)
    - nitric oxide is a vasodilator
      - PDE-5 helps to break down nitric oxide
    - mechanism
      - blocks PDE-5, increasing NO, and thus vasodilation
    - side effects
headache

Complications

Cor pulmonale
- right-sided congestive heart failure secondary to pulmonary disease
Chronic hypoxemic respiratory failure