Cor pulmonale, also known as pulmonary heart disease, is a disease in which pulmonary vascular resistance increases due to lesions of bronchial-lung tissue, thorax, or pulmonary vessels, resulting in pulmonary arterial hypertension and subsequently structural and/or functional changes of the right ventricle. According to the onset and disease duration, it can be divided into acute and chronic cor pulmonale. Acute cor pulmonale is common in acute massive pulmonary embolism.
Etiology
According to the different sites of the primary disease, it can be divided into the following categories.
In bronchial and pulmonary diseases, COPD is the most common, accounting for about 80% - 90%. Others include interstitial lung disease, bronchial asthma, bronchiectasis, and pulmonary tuberculosis.
Thoracic movement disorders are less common. Severe thoracic or spinal deformities and neuromuscular diseases can cause restricted thoracic mobility, lung compression, and bronchial distortion or deformation, resulting in impaired lung function. Inadequate airway drainage and recurrent infections of the lungs may cause emphysema or fibrosis.
In pulmonary vascular diseases, idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary arterial hypertension, and pulmonary arteritis can cause increased pulmonary vascular resistance, elevated pulmonary artery pressure, and increased load on the right ventricle, developing into chronic cor pulmonale.
Primary alveolar hypoventilation, congenital oropharyngeal deformities, and sleep apnea hypopnea syndrome can cause hypoxemia, resulting in pulmonary vascular constriction, leading to pulmonary arterial hypertension, and developing into chronic cor pulmonale.
Pathogenesis and pathophysiology
Formation of pulmonary arterial hypertension
Pulmonary vascular contraction plays a key role in the occurrence of hypoxic pulmonary arterial hypertension. Hypoxia, hypercapnia, and respiratory acidosis cause pulmonary vascular contraction and spasm, and hypoxia is the most important factor in the formation of pulmonary arterial hypertension.
When there is hypoxia, the active substances that constrict blood vessels increase. For example, leukotrienes, 5-hydroxytryptamine (5-HT), angiotensin II, and platelet activating factor (PAF) cause pulmonary vascular contraction and increase vascular resistance. The imbalance between endothelium-derived relaxing factor (EDRF) and endothelium-derived constricting factor (EDCF) also plays a certain role in hypoxic pulmonary vascular contraction. Hypoxia increases the permeability of smooth muscle cell membranes to Ca2+, increases intracellular Ca2+ content, and enhances the muscle excitation-contraction coupling effect, directly causing pulmonary vascular smooth muscle contraction.
In hypercapnia, due to excessive production of H+, the blood vessels become more sensitive to the contraction caused by hypoxia, resulting in increased pulmonary arterial pressure.
Pulmonary artery lesions in idiopathic pulmonary arterial hypertension and chronic thromboembolic obstruction in CTEPH are common causes of pulmonary vascular remodeling. Chronic hypoxia in patients with COPD or interstitial lung disease can cause pulmonary vascular contraction and increased wall tension, and various growth factors such as polypeptide growth factors are produced in the lungs during hypoxia, which can directly stimulate the smooth muscle cells of the vessel wall, intimal elastic fibers, and collagen fiber proliferation.
Long-term recurrent COPD and peribronchitis can involve adjacent pulmonary arterioles, causing vasculitis, thickening of the vessel wall, and stenosis, fibrosis, or even complete occlusion of the lumen, increasing pulmonary vascular resistance and causing pulmonary arterial hypertension.
Emphysema leads to increased pressure in the alveoli, compressing the alveolar capillaries, resulting in stenosis or occlusion of the capillary lumen. Rupture of the alveolar wall causes destruction of the capillary network. When the reduction of the alveolar capillary bed exceeds 70%, the pulmonary circulation resistance increases.
Autopsy findings show that some patients with acute exacerbation of chronic cor pulmonale have multiple in situ thrombosis of pulmonary microarteries, causing increased pulmonary vascular resistance and aggravated pulmonary arterial hypertension.
Chronic hypoxia causes secondary polycythemia and increased blood viscosity. Hypoxia can increase aldosterone, leading to water and sodium retention. Hypoxia also causes constriction of the renal arterioles, and reduced renal blood flow also aggravates water and sodium retention and increased blood volume. Increased blood viscosity and increased blood volume can lead to elevated pulmonary artery pressure.
Cardiac lesions and heart failure
Increased pulmonary circulation resistance leads to pulmonary arterial hypertension. The right heart exerts its compensatory function to overcome the increased pulmonary arterial resistance and develops right ventricular hypertrophy. In the early stage of pulmonary arterial hypertension, the right ventricle can still compensate and the end-diastolic pressure remains normal. With the progression of the disease, especially during acute exacerbation, the pulmonary arterial pressure continues to rise, exceeding the compensatory capacity of the right ventricle. The right heart decompensates, the right cardiac output decreases, the residual blood volume at the end of systole of the right ventricle increases, and the end-diastolic pressure increases, promoting the enlargement of the right ventricle and right heart failure.
Damage to other important organs
In addition to affecting the heart, hypoxia and hypercapnia also cause pathological changes in other important organs such as the brain, liver, kidney, gastrointestinal tract, endocrine system, and blood system, causing multi-organ functional damage.
Clinical manifestations
Compensatory stage of lung and heart functions
Symptoms include cough, expectoration, and tachypnea, as well as palpitations, dyspnea, malaise, and decreased labor endurance after activities, occasionally thoracodynia or hemoptysis.
There may be cyanosis and signs of the primary lung disease, such as emphysema, dry and moist crackles, P2 > A2. Systolic murmur may occur in the tricuspid area or the cardiac impulse under the xiphoid process is enhanced, suggesting right ventricular hypertrophy. In some patients, emphysema increases the pressure in the thoracic cavity and hinders the return of the vena cava; there may be jugular vein filling or even distension, or the descent of the diaphragm may cause the liver boundary to move downward.
Decompensatory stage of lung and heart functions
Respiratory failure
Dyspnea is aggravated. There are often headache, insomnia, anorexia, and daytime drowsiness. Some patients even show manifestations of pulmonary encephalopathy such as apathy, trance, and delirium.
Cyanosis is significant. Conjunctiva is congested and edematous. In severe cases, there may be manifestations of increased intracranial pressure such as retinal vascular dilation and optic disc edema. Tendon reflexes are weakened or absent, and pathological reflexes occur. Due to hypercapnia, there may be manifestations of peripheral vascular dilation, such as skin flushing and diaphoresis.
Right heart failure
There are significant tachypnea, palpitations, anorexia, abdominal distension, and nausea.
There are significant cyanosis, distended jugular vein, and increased heart rate. Arrhythmia may occur. Systolic murmur can be heard under the xiphoid process, and even diastolic murmur may occur. The liver is enlarged and tender. Hepatojugular reflux sign is positive. There is edema of the lower extremities. In severe cases, there may be ascites. Few patients may have signs of pulmonary edema and total heart failure.
Auxiliary examination
Chest x-ray
Besides the characteristics of pulmonary and thoracic underlying diseases and acute pulmonary infections, there are also signs of pulmonary arterial hypertension.
Figure 1 Schematic diagram of frontal chest x-ray in chronic cor pulmonale
The right lower pulmonary artery trunk is widened (a), the pulmonary artery segment is protruding (b), and the cardiac apex is convex upward (c).
Electrocardiogram
The positive rate of electrocardiogram for the diagnosis of chronic cor pulmonale is 60.1% - 88.2%. The diagnostic considerations include:
- Mean frontal electrical axis ≥ +90°
- V1R/S ≥ 1
- Severe clockwise rotation (V5R/S ≤ 1)
- RV1 + SV5 ≥ 1.05 mV
- R/S or R/Q ≥ 1 in aVR lead
- V1 - V3 showing QS, Qr, or qr, resembling that in myocardial infarction
- P pulmonale
If there are at least one of the diagnostic considerations, a diagnosis can be established.
Figure 2 Electrocardiogram of chronic cor pulmonale
Right axis deviation, clockwise rotation, P pulmonale, QRS complex in lead V1 showing qR, V5R/S < 1, RV1 + SV5 = 1.5 mV
Echocardiogram
The positive rate of echocardiogram for the diagnosis of cor pulmonale is 60.6% - 87.0%. The diagnostic considerations include:
- The inner diameter of the right ventricular outflow tract ≥ 30 mm
- The inner diameter of the right ventricle ≥ 20 mm
- The thickness of the anterior wall of the right ventricle ≥ 5 mm or the enhanced amplitude of the anterior wall pulsation
- The ratio of the inner diameters of the left and right ventricles < 2
- The inner diameter of the right pulmonary artery ≥ 18 mm or the main pulmonary artery ≥ 20 mm
- The ratio of the right ventricular outflow tract to the left atrium > 1.4
- Signs of pulmonary hypertension in the pulmonary valve curve (low a wave or a wave < 2 mm, or mid-systolic closure sign)
Blood gas analysis
Hypoxemia, even respiratory failure, or concurrent hypercapnia may occur.
Blood tests
Red blood cell count and hemoglobin can increase. Whole blood viscosity and plasma viscosity can increase, and the electrophoresis time of red blood cells is often prolonged. Renal or liver function abnormalities may be accompanied in case of cardiac insufficiency.
Others
Etiological examination of sputum can guide the selection of antibiotics. Pulmonary function tests can be performed in the early stage or remission stage of chronic cor pulmonale for evaluation.
Diagnosis
Based on the history of COPD, chronic bronchitis, emphysema, or other thoracic or pulmonary disease; signs of increased pulmonary artery pressure, enlarged right ventricle or right heart dysfunction, such as jugular vein distension, P2 > A2, enhanced cardiac impulse under the xiphoid process, enlarged and tender liver, positive hepatojugular reflux sign, and lower extremity edema; and signs of widened pulmonary artery and enlarged and hypertrophic right heart in electrocardiogram, chest x-ray film, and echocardiogram; a diagnosis can be established.
Differential diagnosis
Coronary atherosclerotic heart disease (coronary heart disease)
Both chronic cor pulmonale and coronary heart disease are more common in older adults. Coronary heart disease mostly has a typical history of angina pectoris, myocardial infarction, or electrocardiogram manifestations. A history of left heart failure, primary hypertension, hyperlipidemia, and diabetes is more helpful for differentiation. Physical examination, chest x-ray, electrocardiogram, and echocardiogram showing signs of left ventricular hypertrophy and coronary angiography suggesting coronary artery stenosis can be used for identification. When chronic cor pulmonale is concurrent with coronary heart disease, the differentiation is more difficult. The medical history should be asked in detail, and is in combination with physical examination and related heart and lung function tests for identification.
Rheumatic heart disease
The tricuspid valve disease of rheumatic heart disease should be differentiated from the relative tricuspid insufficiency of chronic cor pulmonale. The former often has a history of rheumatic arthritis and myocarditis；other valves such as the mitral valve and aortic valve are often diseased；and x-ray, electrocardiogram, and echocardiogram have special manifestations.
Primary cardiomyopathy
This disease is mostly manifested by whole heart enlargement. There are no history of chronic bronchial and lung diseases and no x-ray manifestations of pulmonary hypertension.
Treatment
Compensatory stage of lung and heart functions
Comprehensive treatment measures can be adopted to delay the progression of bronchial and pulmonary underlying diseases, prevent infections, and reduce or avoid acute exacerbations. Rehabilitation exercises and nutritional supplementation should be strengthened, and when necessary, long-term home oxygen therapy or home non-invasive ventilator treatment can be used to improve the quality of life.
Decompensatory stage of lung and heart functions
The treatment principle is to actively control infections, keep the respiratory tract unobstructed, improve respiratory function, correct hypoxia and/or carbon dioxide retention, control respiratory failure and heart failure, and prevent complications.
Control of infections
Respiratory system infections are common causes of acute exacerbation of chronic cor pulmonale leading to decompensation of lung and heart functions. Active control of infections is required.
Control of heart failure
In patients with chronic cor pulmonale, heart failure can be improved after actively controlling infections, improving respiratory function, and correcting hypoxia and carbon dioxide retention. The urine output increases, and edema subsides. Diuretics and positive inotropic drugs are not routinely used. However, in patients who are ineffective to the above treatments or have severe heart failure, diuretics, positive inotropic drugs, or vasodilators can be appropriately selected.
Diuretics inhibiting the reabsorption of sodium and water in the kidneys increase urine output, eliminate edema, reduce blood volume, and reduce the preload of the right heart. However, after the application of diuretics, hypokalemia, hypochloremic alkalosis, thick expectoration, and blood concentration are prone to occur, and precautions should be taken. Therefore, in principle, mild diuretics should be selected and in combination with potassium-sparing diuretics, and used in small doses and short courses. For example, hydrochlorothiazide 25mg 1 - 3 times a day in combination with spironolactone 20 - 40mg 1 - 2 times a day can be administered.
Due to chronic hypoxia and infection in patients with chronic cor pulmonale, their tolerance to digitalis drugs is low, and they are susceptible to poisoning and arrhythmias. Therefore, the application should be cautious. The indications include:
- Infection controlled, respiratory function improved, and right heart function not improved after diuretic treatment
- Right heart failure as the main manifestation with no obvious infection
- Concurrent supraventricular tachyarrhythmias, such as supraventricular tachycardia and atrial fibrillation (ventricular rate > 100 beats/min)
- Concurrent acute left heart failure
In principle, digitalis drugs with fast onset and excretion should be selected and administered intravenously in small doses (1/2 or 2/3 of the conventional dose). K-strophanthin 0.125 - 0.25mg or lanatoside C 0.2 - 0.4mg diluted with 10% glucose solution can be slowly intravenously injected. Before medication, attention should be paid to correcting hypoxia and preventing hypokalemia to avoid drug toxicity reactions. Hypoxemia and infection can increase the heart rate. Therefore, the heart rate should not be used as an indicator for the application and efficacy assessment of digitalis drugs.
Targeted drugs can be applied for cor pulmonale caused by arterial pulmonary hypertension and CTEPH to reduce pulmonary vascular resistance. However, for cor pulmonale caused by COPD or interstitial lung disease, vasodilators may aggravate ventilation-perfusion imbalance and hypoxia. And while dilating the pulmonary artery, it also dilates the systemic artery, which is prone to cause a decrease in systemic blood pressure and reflexively cause adverse reactions such as an increase in heart rate, a decrease in oxygen partial pressure, and an increase in carbon dioxide partial pressure. Thus, the clinical application of vasodilators is limited.
Prevention of complications
Neuropsychiatric disorders caused by hypoxia and carbon dioxide retention due to respiratory failure are often secondary to COPD. To diagnose pulmonary encephalopathy, cerebrovascular diseases, toxic encephalopathy, and severe electrolyte disorders must be excluded.
Chronic cor pulmonale in the decompensatory stage is often concurrent with various types of acid-base imbalances and electrolyte disorders. The treatment of respiratory acidosis mainly focuses on clearance of airway, correction of hypoxia, and elimination of carbon dioxide retention. Respiratory acidosis concurrent with metabolic acidosis usually requires alkali supplementation, especially when pH < 7.2, 100 ml of 5% sodium bicarbonate should be promptly supplemented. Respiratory acidosis concurrent with metabolic alkalosis is often concurrent with electrolyte disorders such as hyponatremia, hypokalemia, and hypochloremia, and should be supplemented according to the specific situation. Metabolic alkalosis caused by hypokalemia and hypochloremia is mostly iatrogenic and should be prevented.
Arrhythmias are mostly manifested by atrial premature contractions and paroxysmal supraventricular tachycardia, in which chaotic atrial tachycardia is most characteristic. Atrial flutter and atrial fibrillation can also occur. General arrhythmias can heal spontaneously after controlling infections and correcting hypoxia, acid-base imbalance, and electrolyte disorders. If it persists, drugs can be selected according to the type of arrhythmia.
Concurrent shock is less common. Once it occurs, the prognosis is poor. The causes include severe infection, blood loss (mostly caused by upper gastrointestinal hemorrhage), and severe heart failure or arrhythmia.
Due to infection, respiratory failure, and heart failure causing gastrointestinal congestion, and the application of glucocorticoids, chronic cor pulmonale is often concurrent with gastrointestinal hemorrhage, which requires preventive treatment.
Disseminated intravascular coagulation (DIC) should be prevented.
Deep vein thrombosis can be prevented with low-dose unfractionated heparin or low molecular weight heparin.
Prognosis
Chronic cor pulmonale often has recurrent acute exacerbations. With the impairment of lung function, the condition is gradually exacerbated. Most patients have a poor prognosis, and the mortality is about 10% - 15%. However, active treatment can prolong life and improve the quality of life of patients.
Prevention
Underlying diseases in the bronchi, lungs, and pulmonary vessels that can cause pulmonary arterial hypertension should be prevented.