Chronic cor pulmonale

01Definition and overview

Cor pulmonale means a right ventricle changed by lung disease: hypertrophy and dilatation, and in the end failure, caused by pulmonary hypertension that arises from disease of the lungs, the chest wall or the control of breathing. Right ventricular failure caused by disease of the left heart is excluded, however alike the two look at the bedside. Acute cor pulmonale is the sudden strain of a previously normal right ventricle, usually from a large pulmonary embolism. The chronic form develops over years and is the subject here.

The pulmonary circulation carries the whole cardiac output at a low pressure and a low resistance: the normal mean pulmonary artery pressure at rest is about 14 mmHg. Pulmonary hypertension is defined as a mean pulmonary artery pressure above 20 mmHg at rest, measured at right heart catheterisation; the older threshold was 25 mmHg. The pulmonary artery wedge pressure, which reflects the left atrial pressure, and the pulmonary vascular resistance (the pressure drop across the lungs divided by the cardiac output, in Wood units) separate the types:

In lung disease, a pulmonary vascular resistance above 5 Wood units marks severe pulmonary hypertension. Pulmonary hypertension is grouped by its cause, because the cause decides the treatment:

In the strict sense cor pulmonale could follow any group except left heart disease (group 2) and congenital heart disease. In practice the term is used for group 3, the right heart disease of chronic lung disease and hypoxia, and the other groups are named by their cause.

02Etiology and pathophysiology

Causes

How lung disease loads the right ventricle

1. 1

   Hypoxic vasoconstriction

   Small pulmonary arteries constrict when the oxygen in their alveoli falls, which normally diverts blood to well-ventilated lung. When the hypoxia is widespread and lasting, the whole bed constricts, and acidosis and hypercapnia make it worse.
2. 2

   Remodelling

   Sustained hypoxia, inflammation and, in smokers, tobacco smoke itself thicken the intima and media of the small arteries and lay muscle into arterioles that normally have none. The endothelium makes less nitric oxide and prostacyclin and more endothelin. The raised pressure becomes fixed.
3. 3

   Loss and compression of vessels

   Emphysema and fibrosis destroy the capillary bed, hyperinflated lungs compress the vessels, and secondary polycythaemia makes the blood more viscous, so the resistance rises further.
4. 4

   The right ventricle

   The thin-walled right ventricle is built for a low-pressure circuit. It first adapts with hypertrophy. When the load outruns it, it dilates, the tricuspid valve leaks, and the septum is pushed towards the left ventricle, which fills less, so the cardiac output falls.

In COPD the pulmonary hypertension is usually mild to moderate and rises slowly over years, with bigger rises during exercise, sleep and exacerbations. A minority of patients have pulmonary hypertension out of proportion to their lung disease, often with a very low gas transfer, only mild to moderate airflow limitation and no hypercapnia. This pulmonary vascular pattern behaves more like a disease of the vessels themselves and needs specialist assessment, as does any case in which another cause, such as chronic thromboembolism or left heart disease, may add to the pressure.

Fluid retention in hypercapnic COPD is not simply a failing right ventricle. Hypercapnia and hypoxaemia lower kidney blood flow and activate the renin-angiotensin-aldosterone system and vasopressin, so the kidneys keep salt and water, and oedema can appear while the right heart still pumps fairly well. It often appears first during an exacerbation.

03Clinical features

The symptoms are mostly those of the lung disease: breathlessness, cough and fatigue. Pulmonary hypertension adds breathlessness out of proportion to the lung function and falling exercise tolerance, and when severe, chest pain, light-headedness or fainting on exertion. Right heart failure brings ankle swelling, abdominal swelling, discomfort under the right ribs from a congested liver, and loss of appetite.

• Signs of the lung disease and its gases: central cyanosis, hyperinflation, plethora from polycythaemia; with hypercapnia, warm hands, a bounding pulse, a flapping tremor, and drowsiness or confusion when severe.
• Signs of pulmonary hypertension: a left parasternal heave, felt below the xiphoid in a hyperinflated chest; a loud pulmonary second sound; a right ventricular third sound; sometimes the early diastolic murmur of pulmonary regurgitation.
• Signs of right heart failure: a raised jugular venous pressure with large v waves; the pansystolic murmur of tricuspid regurgitation at the lower left sternal edge, louder on inspiration; a tender and sometimes pulsatile liver; ascites and pitting oedema.

Hyperinflation muffles the heart sounds and hides the heave, so the signs are less reliable in COPD. Oedema has other causes too, such as calcium channel blockers, a low albumin and immobility. Fainting on exertion, signs of right heart failure and a saturation that falls sharply on effort mark severe disease.

04Diagnosis and management

Tests

• ECG: P pulmonale (a P wave taller than 2.5 mm in lead II), right axis deviation, a dominant R wave in V1, right bundle branch block, and T-wave inversion in V1 to V3. In COPD the voltages are low and the ECG is insensitive, so a normal one does not exclude pulmonary hypertension.
• Chest X-ray: enlarged central pulmonary arteries with pruned peripheral vessels, a right descending pulmonary artery wider than about 16 mm, an enlarged right heart, and the lung disease itself.
• Echocardiography, the key screening test. The peak velocity of the tricuspid regurgitant jet estimates the pulmonary artery systolic pressure, and with other signs, from at least two of three groups (the ventricles, the pulmonary artery, and the inferior vena cava and right atrium), it gives the probability of pulmonary hypertension. It also shows a dilated, poorly contracting right ventricle, a flattened septum that makes the left ventricle D-shaped, a dilated inferior vena cava, and any left heart or valve disease. Hyperinflated lungs often give poor views; cardiac MRI then shows the right ventricle well.
• Blood tests: NT-proBNP, raised by right ventricular strain and used to follow it; a full blood count for polycythaemia; arterial blood gases for hypoxaemia and hypercapnia; kidney, liver and thyroid function.
• Lung function with gas transfer, and high-resolution CT of the chest, to define the lung disease and its severity. A gas transfer much lower than the spirometry would suggest points to vascular disease. On CT, a pulmonary artery wider than the aorta suggests pulmonary hypertension.
• Overnight oximetry or a sleep study, for sleep apnoea and nocturnal hypoventilation.
• A ventilation-perfusion scan in unexplained pulmonary hypertension, to look for chronic thromboembolic disease, which surgery can cure.
• Right heart catheterisation measures the pressures, wedge pressure and resistance. In lung disease it is done when the result would change treatment: suspected severe pulmonary hypertension, suspected pulmonary arterial or chronic thromboembolic hypertension, or assessment for lung transplantation or lung volume reduction.

Treating the lung disease and the hypoxaemia

The treatment is aimed at the lung disease and the low oxygen behind the pulmonary hypertension.

• The lung disease: stopping smoking, inhaled bronchodilators, pulmonary rehabilitation, early treatment of exacerbations, and vaccination against influenza, pneumococcus and COVID-19; antifibrotic drugs in progressive pulmonary fibrosis.
• Long-term oxygen therapy, by the criteria in the table, for at least 15 hours a day, through a concentrator and nasal cannulae, to keep the PaO2 above 8 kPa (a saturation of about 90 per cent or more) without a dangerous rise in carbon dioxide. Two trials in the early 1980s showed that it prolongs life in hypoxaemic COPD; it also slows the rise in pulmonary pressure. In moderate hypoxaemia it does not prolong life. Smoking near oxygen causes burns and house fires, so oxygen is not usually prescribed to people who still smoke.
• Ventilatory support: non-invasive ventilation at night for chronic hypercapnic respiratory failure, as in COPD with persistent hypercapnia after an exacerbation, obesity hypoventilation, and chest wall or neuromuscular disease; continuous positive airway pressure for obstructive sleep apnoea.

Treating the right heart

• A loop diuretic for oedema, given gently with daily weights. Too much diuresis starves the pressure-loaded right ventricle of filling and lowers the cardiac output, and the metabolic alkalosis it causes can suppress breathing and raise the CO2. Potassium, creatinine and gases are checked.
• Venesection when polycythaemia keeps the haematocrit above about 55 per cent despite oxygen.
• Digoxin only for atrial fibrillation. It does not help the right ventricle otherwise, and hypoxia and a low potassium make toxicity likelier.
• Anticoagulation only for another reason, such as atrial fibrillation, venous thromboembolism or chronic thromboembolic disease.
• Lung transplantation for selected patients with end-stage lung disease.

Acute decompensation

An exacerbation of the lung disease is the usual trigger. It is treated as such: controlled oxygen to a saturation of 88 to 92 per cent in patients at risk of hypercapnia, bronchodilators, corticosteroids and antibiotics as indicated, non-invasive ventilation for a respiratory acidosis, and diuretics for fluid overload. A failing right ventricle tolerates low blood pressure, fluid overload, hypoxia and acidosis poorly, so severe right heart failure is managed in intensive care, where the trigger is reversed, fluid is balanced and the blood pressure is supported.

05Epidemiology

Pulmonary hypertension affects about 1 per cent of people worldwide, and lung disease, chiefly COPD, is its second commonest cause after left heart disease. In COPD it becomes commoner as the disease advances: mild pulmonary hypertension is common in advanced COPD, but severe pulmonary hypertension is found in only about 1 to 5 per cent of patients with advanced COPD and chronic respiratory failure. In interstitial lung disease, pulmonary hypertension (by the older threshold of 25 mmHg) is found in about 8 to 15 per cent at diagnosis, 30 to 50 per cent in advanced disease and over 60 per cent at the end stage. Because COPD is so common, cor pulmonale is mostly a disease of older long-term smokers and, where wood and other biomass fuels are burned indoors, of people exposed to the smoke. Chronic mountain sickness, with polycythaemia and pulmonary hypertension, affects some people who live permanently at high altitude, as in the Andes and Tibet.

06Prognosis

Pulmonary hypertension in chronic lung disease predicts death independently of the lung function, and the higher the resistance, the shorter the survival; severe pulmonary hypertension carries a poor outlook. In the early oxygen trials, which enrolled patients with COPD and severe hypoxaemia, many of whom had had ankle oedema, only about 3 in 10 of those without long-term oxygen were alive at 5 years, and oxygen for 15 hours or more a day improved survival. Once the right heart has failed, the outlook depends on the lung disease and on how well the hypoxaemia and hypercapnia can be corrected. Death usually comes from respiratory failure during an exacerbation. Lung transplantation extends life in selected patients.