Cor Pulmonale

Overview

• Also known as pulmonary heart disease
• Characterized by structural alteration and dysfunction of the right ventricle (RV) caused by primary lung disease
• Can be acute or chronic:
  • Acute cor pulmonale is most commonly caused by massive pulmonary embolism. 
  • Chronic cor pulmonale has a slow and progressive course resulting from worsening lung disease.
• Chronic lung disease with cor pulmonale indicates a poor prognosis.

Etiology and Epidemiology

Etiology

• Cor pulmonale develops from increased right-sided filling pressures from long-term pulmonary hypertension (PH) associated with lung disease.
• Pulmonary hypertension is defined as:
  • Increased blood pressure in pulmonary arteries
  • Mean pulmonary arterial pressure of > 20 mm Hg (at rest, measured by right heart catheterization; normal = 14–20 mm Hg)
  • For pre-capillary PH (disease confined to pulmonary arterial bed), criteria include pulmonary vascular resistance (PVR) of ≥ 3 Wood units).
• PH Classification (based on the 6th World Symposium of Pulmonary Hypertension proceedings):
  • Group 1: Pulmonary arterial hypertension
  • Group 2: PH due to left heart disease
  • Group 3: PH due to lung disease and/or hypoxia
    • Obstructive lung disease
    • Restrictive lung disease
    • Mixed obstructive/restrictive pattern
    • Hypoxia (without lung disease)
    • Developmental lung disorders
  • Group 4: PH due to pulmonary artery obstructions
  • Group 5: PH with unclear and/or multifactorial mechanisms
• RV dysfunction resulting from left-sided heart disease and congenital heart disease (group 2 PH) is not cor pulmonale.

Epidemiology

• Prevalence: limited data; right heart catheterization is not regularly performed for patients at risk
• Cor pulmonale: 6%–7% of all types of adult heart disease in the United States
• Half of the cases in North America are due to chronic obstructive pulmonary disease (COPD).

Pathophysiology

• Hypoxic pulmonary vasoconstriction
  • To limit blood flow to hypoxic alveoli, low oxygen leads to pulmonary vasoconstriction, diverting blood to the better-ventilated alveoli.
  • Changes in vascular mediators: 
    • ↑ Endothelin-1 (vasoconstrictor, smooth muscle proliferation)
    • ↓ Endothelial nitric oxide synthase production: ↓ nitric oxide (vasodilator)
    • ↓ Prostacyclin (vasodilator)
  • Changes in ion channels:
    • Chronic hypoxia reduces expression of potassium channels, increases intracellular calcium ⇒ pulmonary artery muscle contraction
• Pulmonary vascular remodeling
  • Vascular alterations occur: neomuscularization of arterioles, intimal thickening, medial hypertrophy
  • Inflammation and effects of cigarette smoking are potential mechanisms, as COPD-afflicted patients without hypoxemia have also been found to have endothelial dysfunction in pulmonary arteries. 
• Above factors lead to increased pulmonary vascular resistance. 
  • As resistance increases, as does pulmonary artery pressure and, eventually, RV afterload.
  • RV adapts to slowly increasing pulmonary artery pressure initially by dilation; leads to hypertrophy.
  • Consequent effect is RV dysfunction and failure.
• RV hypertrophy does not occur with acute cor pulmonale.

Clinical Presentation

Symptoms

• Dyspnea: caused by the underlying pulmonary disease and resulting cor pulmonale
• Chest pain: from increased oxygen demand and increased stress on the RV
• Syncope: inability to increase cardiac output with exertion or exercise
• Peripheral edema and increased abdominal girth: from right-sided heart failure and hepatic congestion
• Anorexia, nausea/vomiting, right upper quadrant pain: from hepatic congestion

Signs

Inspection

• Signs of high right-sided filling pressures:
  • RV heave
  • Elevated jugular venous pressure
  • Prominent V waves due to tricuspid regurgitation (jugular vein exam)
• Signs of hepatic congestion from right-sided heart failure:
  • Hepatomegaly and/or pulsatile liver
  • Ascites
  • Lower-extremity edema
• Signs of hypoxemia:
  • Increased respiratory rate
  • Cyanosis
  • Clubbing

Chest auscultation

• Lungs: depends on underlying pulmonary disease
• Heart: accentuated P2, blowing holosystolic murmur at the left lower sternal border (tricuspid regurgitation murmur), and S3 gallop

Diagnosis

Right heart catheterization

• Gold standard to confirm pulmonary hypertension, but not required in all patients
• Indications affected by:
  • Severity of PH
  • Potential for PH–specific treatment
  • Life expectancy of patient
  • Possibility of lung transplantation
• Results: mean pulmonary arterial pressure (mPAP) ≥ 20 mm Hg

Doppler echocardiography

• Initial test of choice 
• RV enlargement (dilation and/or hypertrophy)
• Paradoxical movement of interventricular septum 
  • The septum is shifted toward the left ventricle, resulting in flattening of the ventricular septum during systole.
• Increased pulmonary artery systolic pressure 
• Tricuspid regurgitation with a high-velocity regurgitant jet by Doppler
• Rules out left-sided heart failure

Laboratory studies

• Arterial blood gases: possible hypoxia ± hypercarbia and acidosis depending on degree of lung disease
• Elevated B-type natriuretic peptide (BNP) and N-terminal BNP
• CBC may show ↑ hemoglobin, ↑ hematocrit (from secondary erythrocytosis caused by hypoxia)

Electrocardiogram

• P pulmonale
• Right axis deviation, right ventricular hypertrophy

Chest X-ray

• Central pulmonary artery and hilar enlargement
• Cardiomegaly (from RV enlargement)
• Changes consistent with underlying pulmonary disease

Pulmonary function test

• Shows obstructive and/or restrictive defects depending on underlying lung diseases

Chest computed tomography (CT) scan

• High-resolution: signs of interstitial lung disease or emphysema
• Angiogram: acute pulmonary embolism in the case of acute cor pulmonale; enlarged pulmonary artery

Ventilation-perfusion scan

• Preferred initial test for chronic thromboembolism
• Greater sensitivity for chronic pulmonary thromboembolism than CT angiogram

Cardiac magnetic resonance imaging (MRI)

• Not routinely used but shows increased RV size

Management

Management is first focused on the underlying cause of cor pulmonale.

• Smoking cessation
• Oxygen therapy:
  • Only treatment that slows down progression of PH in COPD
  • Relieves pulmonary vasoconstriction, thereby improving cardiac output and tissue perfusion
  • Indications:
    • PaO₂ ≤ 55 mm Hg or oxygen saturation < 88% in general
    • PaO₂ ≤ 59 mm Hg or oxygen saturation ≤ 89% for patients with cor pulmonale, right heart failure, or hematocrit > 55% 
• Pharmacotherapy:
  • For chronic right heart failure or elevated RV filling pressures: diuretics (but monitor for volume depletion)
  • For primary pulmonary arterial hypertension or group 1 PH: 
    • Calcium channel blockers (leads to pulmonary artery vasodilation), prostaglandin analogs, endothelin-receptor antagonists, phosphodiesterase-5 (PDE-5) inhibitors
    • These medications have limited benefit in group 3 PH and in some cases may be harmful.
  • Treatment of venous thromboembolism: anticoagulants
• Surgical management:
  • COPD patients with hematocrit ≥ 65%: phlebotomy
  • Surgical embolectomy in massive pulmonary embolism with acute cor pulmonale (if thrombolysis fails or is contraindicated)
  • Lung ± heart transplantation: for patients who failed therapy