What is Cor pulmonale?

What is Cor Pulmonale

Cor pulmonale is right ventricular hypertrophy and/or dilation caused by pulmonary hypertension that results from diseases affecting lung structure or function, excluding left heart disease or congenital heart disease. 1, 2, 3

Core Definition and Pathophysiology

Cor pulmonale represents the cardiac consequences of pulmonary vascular disease, where the right ventricle (RV) must work against increased afterload from elevated pulmonary vascular resistance (PVR). 4, 5 The condition develops when mean pulmonary arterial pressure (mPAP) exceeds normal values—historically defined as >25 mmHg, though recent definitions suggest >20 mmHg may be more appropriate for early detection. 5

Key Pathophysiologic Mechanisms

The RV is anatomically designed to pump against low resistance and adapts poorly to acute pressure increases compared to the left ventricle. 1 When faced with chronically elevated PVR:

• Initial compensation: The RV hypertrophies and develops isovolumic contraction/relaxation phases, increasing systolic pressure while maintaining cardiac output 1
• Decompensation: Progressive RV dilation occurs with rising right atrial pressure, declining cardiac output, and paradoxically falling pulmonary artery pressure despite persistently elevated PVR—an ominous clinical sign 1
• Ventricular interdependence: RV dilation causes leftward septal shift, impeding left ventricular filling and reducing systemic perfusion 1

Major Etiologic Categories

Group 3 Pulmonary Hypertension (Most Common)

Chronic obstructive pulmonary disease (COPD) is by far the leading cause of cor pulmonale, accounting for the vast majority of cases. 1, 4 Other respiratory causes include:

• Interstitial lung disease 1
• Sleep-disordered breathing and obesity-hypoventilation syndrome 1
• Chronic hypoventilation syndromes 1
• Chronic exposure to high altitude 1

Mechanisms in COPD

The pathophysiology involves multiple factors beyond simple hypoxic vasoconstriction:

• Chronic alveolar hypoxia induces pulmonary vascular remodeling with intimal thickening and medial hypertrophy 1, 4
• Loss of vascular bed from emphysematous destruction 5
• Primary pulmonary arterial lesions resembling pulmonary arterial hypertension in some patients 5
• Hypercapnia and acidosis further increase PVR 3

Clinical Spectrum and Severity

Typical Presentation in COPD

Most COPD patients with cor pulmonale have mild to moderate pulmonary hypertension, with resting mPAP typically 20-35 mmHg. 4 However, pressures can increase significantly during:

• Exercise 4
• Sleep 4
• Acute exacerbations 4

"Disproportionate" Pulmonary Hypertension

A critical subset (<5% of COPD patients) develops severe or "disproportionate" PH with mPAP >40 mmHg. 1, 4 These patients exhibit:

• Mild to moderate airflow obstruction 1
• Severe hypoxemia with hypocapnia (not hypercapnia) 1
• Very low diffusing capacity for carbon monoxide 1
• Possible genetic predisposition (5-HTT polymorphism) 1

This pattern suggests a different biological mechanism—primary pulmonary vascular disease occurring in the presence of, rather than because of, lung disease. 1

Diagnostic Approach

Clinical Recognition

Physical examination has poor sensitivity for detecting moderate cor pulmonale, particularly in obese patients. 6 Key findings when present include:

• Elevated jugular venous pressure 6
• Right ventricular heave 6
• Loud pulmonary second heart sound 1, 6
• Tricuspid regurgitation murmur 6
• Peripheral edema 1, 6

Echocardiographic Criteria (Primary Screening Tool)

Transthoracic echocardiography is the primary diagnostic modality, though accuracy decreases in advanced lung disease due to hyperinflation. 6 Subcostal views often provide adequate visualization. 6

Severity stratification by tricuspid regurgitation velocity (TRV): 6

• No cor pulmonale: TRV ≤2.8 m/s (PA systolic pressure ≤36 mmHg)
• Mild cor pulmonale: TRV 2.9-3.4 m/s (PA systolic pressure 37-50 mmHg)
• Moderate-severe cor pulmonale: TRV >3.4 m/s (PA systolic pressure >50 mmHg)

Additional echocardiographic findings: 6

• RV/LV basal diameter ratio >1.0 indicates RV enlargement
• Left ventricular eccentricity index >1.1 suggests RV pressure overload
• RV outflow Doppler acceleration time <105 msec indicates increased PVR
• Inferior vena cava diameter >21 mm with decreased inspiratory collapse suggests elevated right atrial pressure

Right Heart Catheterization

Right heart catheterization remains the gold standard for confirming pulmonary hypertension (mPAP ≥25 mmHg historically, ≥20 mmHg by newer definitions). 6, 5 However, routine catheterization is not recommended because simpler measurements (FEV1, arterial blood gases) provide similar prognostic information. 7

Indications for catheterization in advanced COPD: 7

• Diagnosis or exclusion of PH in surgical candidates (lung transplantation, lung volume reduction)
• Suspected disproportionate PH requiring specific evaluation

Clinical Pitfalls

Suspect cor pulmonale when: 7

• Clinical deterioration is disproportionate to pulmonary function tests
• Markedly reduced diffusing capacity (DLCO) is present
• Symptoms exceed expectations based on FEV1

Acute vs. Chronic Cor Pulmonale

Acute Right Heart Failure

Acute RHF occurs from abruptly increased RV afterload (massive pulmonary embolism, acute hypoxia) or decreased RV contractility (RV infarction, myocarditis). 1 The RV cannot acutely adapt to pressure increases, leading to:

• Steep decline in stroke volume with minimal pressure increase 1
• Acute RV dilation with severe tricuspid regurgitation 1
• Diastolic ventricular interdependence causing LV underfilling 1

Chronic Cor Pulmonale in Children

In chronic lung disease of infancy (bronchopulmonary dysplasia), cor pulmonale develops from: 1

• Reduced alveolar and arterial number from impaired lung development
• Medial hypertrophy and abnormal peripheral muscularization of arteries
• Alveolar hypoxia-induced vasoconstriction

Peripheral chemoreceptor dysfunction may occur in severely affected infants, potentially increasing SIDS risk. 1

Management Principles

Treatment of Underlying Lung Disease

Treatment is primarily directed at the underlying pulmonary disorder rather than right ventricular failure per se. 3 This includes:

• Aggressive management of COPD exacerbations 2
• Bronchodilators (beta-agonists, anticholinergics, theophylline) 2
• Corticosteroids when indicated 2, 3
• Treatment of respiratory infections 2

Long-Term Oxygen Therapy (LTOT)

LTOT is the logical and evidence-based treatment since chronic alveolar hypoxia is the major determinant of elevated PAP and PVR. 4 LTOT stabilizes, attenuates, or sometimes reverses PH progression, though PAP rarely normalizes completely. 4

Vasodilators and PAH-Specific Therapies

There is currently no evidence supporting routine use of PAH-approved drugs in COPD patients with PH. 4, 5 However, these agents (prostacyclin, endothelin receptor antagonists, sildenafil) could be considered in the small subset with severe, disproportionate PH (mPAP >40 mmHg), though controlled studies are lacking. 4, 5

The rationale for selective use is that some COPD patients have PAH-like primary pulmonary arterial lesions that might respond to targeted therapy. 5

Adjunctive Therapies

• Diuretics: For volume overload and peripheral edema 2
• Phlebotomy: Controversial; may be considered for severe polycythemia 2
• Anticoagulation: Primarily for vascular obliterative types (chronic thromboembolic disease) 2, 3
• Digoxin: Limited role; use is controversial 2

Surgical Options

• Lung transplantation or heart-lung transplantation: For selected patients when medical therapy fails 3
• Pulmonary thromboendarterectomy: For chronic thromboembolic pulmonary hypertension 2

Important Clinical Caveats

The severity of pulmonary hypertension is usually poorly correlated with the severity of underlying lung disease, particularly in COPD. 7 This discordance should prompt evaluation for:

• Disproportionate PH requiring different management
• Coexisting conditions (left heart disease, thromboembolic disease, sleep apnea)
• Genetic susceptibility to vascular remodeling

Declining pulmonary artery pressure in the setting of persistently elevated PVR indicates RV decompensation and is an ominous finding, not improvement. 1