What is cor pulmonale and how is it managed?

Cor Pulmonale: Definition and Management

Definition and Pathophysiology

Cor pulmonale is right ventricular hypertrophy and/or dilation caused by pulmonary hypertension (PH) resulting from diseases affecting lung structure and function, with chronic obstructive pulmonary disease (COPD) being the leading cause. 1, 2

Key Pathophysiologic Mechanisms

• Pulmonary vascular resistance increases primarily due to chronic alveolar hypoxia, which induces pulmonary vascular remodeling and vasoconstriction 2
• The right ventricle (RV) is coupled to a low-resistance, high-compliance pulmonary circulation and adapts poorly to acute pressure increases compared to volume changes 3
• RV stroke volume declines steeply with even modest increases in afterload, unlike the left ventricle which tolerates pressure increases better 3
• Chronic hypoxemia, hypercapnia, and respiratory acidosis all contribute to increased RV afterload 1

Ventricular Interdependence

• RV dilation causes leftward shift of the interventricular septum, increasing LV end-diastolic pressure while reducing LV transmural filling pressure 3
• This mechanical interaction impedes LV diastolic filling and contributes to systemic hypoperfusion 3
• Elevated right-sided filling pressures cause coronary sinus congestion, reducing coronary blood flow and potentially provoking RV ischemia 3

Diagnostic Approach

Clinical Evaluation

Physical examination has poor sensitivity for detecting moderate cor pulmonale, but key findings include: 4

• Raised jugular venous pressure
• Right ventricular heave (parasternal lift)
• Loud pulmonary second heart sound (P2)
• Tricuspid regurgitation murmur
• Peripheral edema
• Central cyanosis 4

Electrocardiography

ECG findings suggestive of cor pulmonale include: 4

• Right axis deviation for age
• Right atrial enlargement (P pulmonale)
• Right ventricular hypertrophy
• In acute cor pulmonale: S1Q3T3 pattern, S1S2S3 pattern, negative T waves in right precordial leads, transient right bundle branch block 4

Echocardiographic Criteria (Gold Standard for Screening)

The European Respiratory Society provides specific quantitative criteria for diagnosis: 4

RV Enlargement and Dysfunction

• RV/LV basal diameter ratio >1.0 indicates RV enlargement 4
• Flattening of interventricular septum (LV eccentricity index >1.1 in systole and/or diastole) suggests RV pressure overload 4
• RA area (end-systole) >18 cm² indicates right atrial enlargement 4

Pulmonary Hypertension Assessment

• Tricuspid regurgitation velocity >3.4 m/s (corresponding to PA systolic pressure >50 mmHg) indicates likely pulmonary hypertension 4
• RV outflow Doppler acceleration time <105 msec and/or midsystolic notching suggests increased PVR 4
• Early diastolic pulmonary regurgitation velocity >2.2 m/sec indicates elevated PA pressure 4
• Pulmonary artery diameter >25 mm suggests pulmonary hypertension 4
• IVC diameter >21 mm with decreased inspiratory collapse (<50% with sniff or <20% with quiet inspiration) suggests elevated RA pressure 4

Severity Grading

• No cor pulmonale: TR velocity ≤2.8 m/s, PA systolic pressure ≤36 mmHg 4
• Mild cor pulmonale: TR velocity 2.9–3.4 m/s, PA systolic pressure 37–50 mmHg 4
• Moderate to severe cor pulmonale: TR velocity >3.4 m/s, PA systolic pressure >50 mmHg 4

Right Heart Catheterization

• Remains the gold standard for confirming pulmonary hypertension with mean PAP ≥25 mmHg (traditional definition) or ≥20 mmHg (revised Nice criteria) 4, 5
• In COPD, resting PAP typically ranges 20-35 mmHg in stable disease 2
• **A minority (<5%) of COPD patients exhibit "disproportionate" severe PH** (PAP >40 mmHg), suggesting PAH-like vascular components 2, 5

Imaging Pitfalls

Echocardiographic assessment may be challenging in patients with hyperinflated lungs due to COPD, but subcostal views usually provide adequate visualization 4

Management Strategy

Treatment of Underlying Lung Disease (Primary Approach)

Treatment is primarily directed at the underlying pulmonary disorder rather than RV failure per se. 1

For COPD-Related Cor Pulmonale

Bronchodilator therapy should be optimized: 3

• β2-agonists and/or anticholinergics
• Consider combination therapy if single agents insufficient
• Theophylline can improve nocturnal oxygen desaturation 3

Inhaled corticosteroids may be considered: 3

• When FEV1 reversibility >10% predicted after bronchodilators
• Fast rate of FEV1 decline (>50 mL/year) 3
• Doses ≥1,000 μg/day should use large-volume spacer or dry-powder system 3

Oral corticosteroids only when clear functional benefit: 3

• Example: increase in post-bronchodilator FEV1 of 10% predicted AND absolute increase ≥200 mL
• Reduce to lowest effective dose due to side effects (osteoporosis, muscle weakness, diabetes) 3

Long-Term Oxygen Therapy (LTOT) - Life-Saving Intervention

LTOT is the only treatment proven to improve survival in patients with COPD and chronic respiratory failure. 3, 2

Indications for LTOT

• Respiratory failure during stable 3-4 week period despite optimal therapy 3
• PaO2 ≤7.3 kPa (55 mmHg) with or without hypercapnia 3
• Some countries use broader criteria: PaO2 7.3-7.9 kPa (55-59 mmHg) with evidence of tissue hypoxia 3

LTOT Effects

• Stabilizes or attenuates progression of PH, sometimes reverses it 2
• PAP seldom returns to normal even with LTOT 2
• Declining PAP in the setting of high PVR is an ominous clinical finding indicating decompensation 3

Acute Oxygen Therapy

During acute exacerbations: 3

• Start at low dose (24% by Venturi mask or 1-2 L/min by nasal cannulae)
• Goal: raise SaO2 to ≥90% and/or PaO2 to ≥8.0 kPa (60 mmHg) without elevating PaCO2 by >1.3 kPa or lowering pH to <7.25 3
• Monitor arterial blood gases regularly and adjust oxygen dose 3

Treatment of Cardiovascular Sequelae

Only oxygen produces specific vasodilation for pulmonary hypertension induced by hypoxic vasoconstriction. 3

Diuretics

• Can reduce edema but use carefully to avoid reducing cardiac output and renal perfusion 3
• Risk of electrolyte imbalance 3

Vasodilators

• Use of other vasodilators usually limited by systemic circulation effects 3
• Vasodilators (prostacyclin, endothelin receptor antagonists, sildenafil) could be considered in patients with severe PH (PAP >40 mmHg), but controlled studies are lacking 2
• May be effective in selected COPD patients with PAH-like vascular components 5

Medications to Avoid

• The hypoxic myocardium is especially sensitive to digoxin and aminophylline 3
• Avoid sedatives and hypnotics during exacerbations 3

Respiratory Stimulants

Respiratory stimulants are not recommended for patients with COPD on present evidence: 3

• Doxapram may have positive effect during exacerbations of respiratory failure, but noninvasive ventilation may be better alternative 3
• Oral almitrine bismesylate can improve oxygen tension but has many side effects (peripheral neuropathy) and no survival benefit 3

Mucolytics and Antioxidants

Widespread use cannot be recommended on present evidence: 3

• Acetylcysteine showed reduction in frequency of acute exacerbations in one 6-month study 3
• No evidence to support prescription during acute exacerbations 3

Supportive Measures

• Encourage sputum clearance by coughing and consider physiotherapy 3
• Nutritional interventions aimed at achieving ideal body weight; avoid high-carbohydrate diets to reduce CO2 production 3
• Psychosocial support and patient education to improve quality of life 3

Advanced Therapies

When medical therapies fail, lung or heart-lung transplantation has become a possibility for selected patients 1

Prognosis and Monitoring

• Pulmonary hypertension in COPD is slowly progressive and its presence implies poor prognosis 3
• In community surveys, 10-year survival with COPD was approximately 30% 3
• PH may worsen during exercise, sleep, and exacerbations, and these acute increases in afterload can favor development of RHF 2
• At review visits, check: dose and frequency of medications, symptom relief, inhaler technique, smoking status, FEV1, VC, exercise capacity, and respiratory muscle function 3