What is cor pulmonale, a condition characterized by right-sided heart failure due to lung disease, often seen in patients with chronic obstructive pulmonary disease (COPD) or other respiratory issues?

Cor Pulmonale: Definition and Clinical Significance

Cor pulmonale is right ventricular enlargement (hypertrophy and/or dilation) secondary to pulmonary hypertension caused by diseases affecting lung structure or function. 1, 2

Core Pathophysiologic Definition

The condition represents a specific cardiopulmonary syndrome with three defining elements:

• Right ventricular structural changes (hypertrophy progressing to dilation) that develop in response to chronic pressure overload 1, 2
• Pulmonary hypertension as the causative mechanism, traditionally defined as mean pulmonary artery pressure >25 mmHg (revised to >20 mmHg per Nice statement) with pulmonary vascular resistance ≥3 Wood units 1, 3
• Primary lung disease as the underlying etiology, excluding left-sided heart disease (pulmonary capillary wedge pressure must be ≤15 mmHg) 1

Primary Pathophysiologic Mechanisms

The development of cor pulmonale follows a cascade of pulmonary vascular injury:

• Chronic alveolar hypoxia drives the process through hypoxic pulmonary vasoconstriction, which initially is a reversible physiologic response but leads to permanent vascular remodeling over time 4, 1
• Pulmonary vascular bed destruction occurs from emphysematous changes, mechanically reducing the cross-sectional area available for blood flow 4, 1
• Extensive arterial wall remodeling affects all layers of pulmonary vessels, characterized by intimal thickening, proliferation of poorly differentiated smooth muscle cells, and deposition of elastic and collagen fibers 4, 1
• Erythrocytosis in chronic hypoxemic states increases effective pulmonary vascular resistance, further exacerbating the pressure load 4, 1

Right Ventricular Response and Failure Progression

The right ventricle is anatomically designed to handle volume changes, not pressure loads, making it particularly vulnerable to chronic pressure overload:

• Initial compensatory phase involves right ventricular hypertrophy with development of isovolumic phases of contraction and relaxation 4
• Progressive RV dilation follows as the ventricle fails to sustain chronic pressure overload 4
• Ventricular interdependence develops as the dilated right ventricle mechanically affects left ventricular function through septal flattening and leftward shift, increasing left ventricular end-diastolic pressure and impeding diastolic filling 4
• Eventual right ventricular failure occurs with peripheral edema, abdominal distension, and ankle swelling 1

Epidemiology and Clinical Context

COPD is the leading cause of cor pulmonale, far exceeding idiopathic pulmonary fibrosis and obesity-hypoventilation syndrome:

• Prevalence increases with COPD severity, with approximately 50% of patients with severe COPD developing pulmonary hypertension 4
• Most COPD-related pulmonary hypertension is mild to moderate, with resting mean pulmonary artery pressure typically ranging between 20-35 mmHg 3
• Only 1-3% of COPD patients develop "out-of-proportion" severe pulmonary hypertension (mean PAP >40 mmHg), which carries significantly higher mortality 4, 3
• Mortality correlates directly with pulmonary artery pressure: 70% mortality when mean PAP ≥40 mmHg, increasing to 90% at ≥50 mmHg 1

Clinical Significance Beyond Definition

Cor pulmonale represents more than isolated right heart pathology:

• Limits peripheral oxygen delivery, increases dyspnea, and reduces exercise endurance 5
• Associated with higher mortality rates independent of other prognostic variables in COPD 5
• Pulmonary hypertension may worsen acutely during exercise, sleep, and disease exacerbations, with these acute afterload increases favoring development of right heart failure 3
• Heart failure is extremely common in COPD patients independent of cor pulmonale, with prevalence ranging from 20-70%, and 40% of mechanically ventilated COPD patients with hypercapnic respiratory failure showing left ventricular dysfunction 4