Cor Pulmonale

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Chapter 23 Cor Pulmonale

Luca M. Bigatello, MD , Kay B. Leissner, MD, PhD

1 What is cor pulmonale?

The term cor pulmonale was coined by Paul Dudley White in 1931 to indicate heart failure coexistent with a primary pathologic condition of the lung. Subsequent definitions have described pathologic aspects of the right ventricle, such as hypertrophy and dilatation. Recent literature has focused on pathophysiology, diagnosis, and therapy of the continuum of pulmonary hypertension and right ventricular failure. Currently, we can define cor pulmonale as acute or chronic pressure overload of the right ventricle in response to pulmonary artery (PA) hypertension of various causes.

2 What are the subtypes of cor pulmonale?

Cor pulmonale can be acute or chronic.

image In acute cor pulmonale the afterload to the right ventricle can rise in a matter of minutes (e.g., massive pulmonary embolism) giving very little room for compensation. The result will be acute right ventricular dilatation and failure, its severity depending primarily on the degree of acute PA hypertension.

image In chronic cor pulmonale, an increase of right ventricular afterload in the face of slowly developing PA hypertension (e.g., hypoxemia in chronic obstructive pulmonary disease [COPD]) generates a compensatory response of the right ventricle (see later) that will preserve the stroke volume until either the afterload increases excessively or the myocardium fails because of ischemia or other pathologic condition.

3 What is the pathophysiology of right ventricular failure?

Under normal conditions, the pulmonary circulation is a low-resistance circuit, and the right ventricle generates the same stroke volume as the left ventricle with end-systolic pressures that are just 20% to 25% of those in the left ventricle. The low pressure within the thin free wall of the right ventricle also allows myocardial perfusion to occur both in systole and in diastole. Because of its structure, similar to that of veins rather than arteries, the right ventricle accommodates well additional volume but not higher pressure. When pressure overload occurs acutely, the right ventricle can only dilate and, if the pressure is sufficiently elevated, fail. Chronically, in response to increased systolic workload the free wall of the right ventricle hypertrophies and becomes similar to the left ventricle. Laplace’s law helps explaining the evolution from hypertrophy to dilatation and failure (Fig. 23-1): In a thin-wall chamber, an increase in intraluminal pressure increases wall stress unless thickness increases or the internal radius decreases. As the right ventricle hypertrophies, myocardial perfusion becomes limited to diastole, making its myocardium more susceptible to ischemia, and thus leading to dilatation and failure.

image

Figure 23-1 Diagrammatic cross-section of the right (RV) and left ventricular (LV) cavities. Left, Normal state. The right ventricle has a thin free wall and a characteristic crescentlike shape. Right, Right ventricular hypertrophy from pressure overload. The right ventricle assumes a spherical shape, thickened free wall, and an overall greater area than the left ventricle, which is normally the larger of the two ventricles.

(From Voelkel NF, Quaife RA, Leinwand LA, et al. Right ventricular function and failure. Report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 114:1883-1891, 2006. Copyright 2006 American Heart Association.)

4 What are the causes of cor pulmonale?

Any process that results in pulmonary hypertension can cause cor pulmonale. Pulmonary hypertension is defined as mean PA pressures > 20 mm Hg at rest or > 30 mm Hg with exercise. The most frequent cause of pulmonary hypertension and cor pulmonale is COPD, due to chronic hypoxemia. In COPD the degree of hypertension is generally moderate, and oxygen supplementation may be effective in relieving some of the pressure load to the right ventricle and delaying failure. Additional causes of cor pulmonale include chronic pulmonary thromboembolic disease, left-sided cardiac abnormalities, untreated obstructive sleep apnea (OSA), interstitial lung diseases, and primary pulmonary hypertension. A comprehensive classification of the diseases of the lung associated with PA hypertension and cor pulmonale is shown in Table 23-1.

Table 23-1 Classification of cor pulmonale according to causative factor

Category Example
Diseases affecting the air passages of the lung and alveoli COPD
Cystic fibrosis
Infiltrative or granulomatous defects
Idiopathic pulmonary fibrosis
Sarcoidosis
Pneumoconiosis
Scleroderma
Mixed connective tissue disease
Systemic lupus erythematosus
Rheumatoid arthritis
Polymyositis
Eosinophilic granulomatosis
Radiation
Malignant infiltration
Diseases affecting thoracic cage movement Kyphoscoliosis
Thoracoplasty
Neuromuscular weakness
Sleep apnea syndrome
Idiopathic hypoventilation
Diseases affecting the pulmonary vasculature Primary disease of the arterial wall
Primary pulmonary hypertension
Pulmonary arteritis
Toxin-induced pulmonary hypertension
Chronic liver disease
Peripheral pulmonary stenosis
Thrombotic disorders Sickle cell diseases
Pulmonary microthrombi
Embolic disorders Thromboembolism
Tumor embolism
Other embolic processes (amniotic fluid, air, fat)
Schistosomiasis and other parasitic infections
Pressure on PAs Mediastinal tumors
Aneurysms
Granulomata
Fibrosis

Modified from Rubin LJ, ed: Pulmonary Heart Disease. Boston, 1984, Martinus Nijhoff, p 4.

5 What is the pathophysiology of PA hypertension?

Hypoxemia and vascular occlusion are the major causes of pulmonary hypertension; both result in an increase in pulmonary vascular resistance and reduction of pulmonary blood flow. Hypoxemia causes local vasoconstriction (hypoxic pulmonary vasoconstriction), which in part corrects ventilation-perfusion match and improves gas exchange. However, chronic vasoconstriction also produces smooth muscle proliferation in the small arteries, leading to increased resistance and increased PA pressure. These architectural changes may promote platelet aggregation leading to thrombus formation that further increases pulmonary artery pressure and pulmonary vascular resistance.

6 Discuss the epidemiology of cor pulmonale, with particular reference to COPD

Cor pulmonale may account for approximately 10% of all admissions for congestive heart failure. COPD is the most frequent cause of cor pulmonale, but the actual incidence is unknown. Pulmonary hypertension in COPD has been reported to occur in 30% to 70% of the cases, a wide range that underlines the lack of large epidemiologic studies of patients with mild to moderate COPD. Severe pulmonary hypertension (mean pressure over 40 mm Hg) is uncommon and does not seem to be closely related to the degree of airflow limitation. Hence, when severe pulmonary hypertension is found in patients with COPD, further causes should be sought, such as chronic embolism, left-sided heart disease, and primary pulmonary hypertension. Regardless, the presence of pulmonary hypertension in COPD is associated with a reduced lifespan.

7 What are the signs and symptoms of cor pulmonale?

Signs and symptoms of cor pulmonale develop slowly over time, as the right ventricle compensates for the increased pressure load, and become more evident as failure sets in.

Symptoms of cor pulmonale include the following:

image Fatigability

image Dyspnea

image Light-headedness

image Chest pain

image Palpitations

image Abdominal fullness, right upper quadrant pain

Signs of cor pulmonale include the following:

image Jugular veins distention

image Prominent A and V waves in the jugular venous pulse trace

image Accentuated pulmonic component of the second heart sound

image Right-sided S4

image Murmurs of tricuspid and pulmonic insufficiency

image Dependent peripheral edema and hepatomegaly

8 What is the mortality associated with cor pulmonale?

Patients with COPD have a 62% 5-year survival rate, whereas patients with COPD and mean PA pressures in excess of 25 mm Hg have a 5-year survival of only 36% and of 30% if peripheral edema is present. It is unclear whether PA hypertension is the cause of death or whether it is a marker of increased mortality.

9 What are the electrocardiographic (ECG) findings associated with right ventricular hypertrophy?

ECG criteria for right ventricular hypertrophy are neither highly specific nor highly sensitive, and in current practice the diagnosis is better made by echocardiography. However, recognizing ECG abnormalities that may be associated with right ventricular hypertrophy remains an important diagnostic tool in the preoperative anesthetic evaluation. ECG findings commonly associated with right ventricular hypertrophy include the following:

image Right axis deviation: QRS negative in lead I, positive in aVR

image Tall R waves in the right precordial leads, deep S waves in the left precordial leads

image Right atrial enlargement: P pulmonale, large P wave, in II and V1

image ST-segment changes in the opposite direction of the QRS (i.e., wide QRS-ST angle)

image Right bundle branch block: wide QRS (> 1.12 seconds); RSR′ in V1 and V2

10 How is the diagnosis of cor pulmonale made?

Once the suspicion of cor pulmonale is raised on clinical grounds (see earlier for signs and symptoms), a number of diagnostic tests are available.

11 What tests can help determine the diagnosis of cor pulmonale?

Laboratory investigations to detect the underlying cause of cor pulmonale may include the following:

image Arterial blood gas analysis with acid-base status.

image Hematocrit to detect polycythemia.

image Coagulation studies to diagnose hypercoagulability, including serum levels of proteins S and C, antithrombin III, factor V Leyden, homocysteine, anticardiolipin antibodies.

image Antinuclear antibody level for connective tissue diseases, such as scleroderma.

image Brain natriuretic peptide may be elevated to compensate right-sided heart failure by diuresis, natriuresis, and vasodilation.

Radiographic findings include the following:

image Chest radiograph

image Enlargement of the central PAs (right PA > 16 mm, left PA > 18 mm) with oligemic peripheral lung fields (Westermark sign)
image Enlargement of the right ventricle, presenting as an increased width of the cardiac silhouette in the posteroanterior view and increased retrosternal space in the lateral view
image Distention of central veins including the azygous vein
image General signs related to the primary lung condition

image Computed tomography and computed tomographic angiography

image Dilation of the main PA diameter (≥ 29 mm has a reported sensitivity of 84% and a specificity of 75% for diagnosing pulmonary hypertension).
image Cardiac dimensions may be evaluated.
image Scans may help in diagnosing the underlying etiology of cor pulmonale, such as pulmonary embolism.

image Ultrafast, ECG-gated computed tomography (CT)

image Ultrafast, ECG-gated CT has been evaluated to study right ventricular function: it may estimate ejection fraction and wall mass with high accuracy.

image Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA)

image MRI can provide highly accurate information about right-sided heart mass, interventricular septal flattening, and biventricular function.
image MRA has been used for the diagnosis of chronic thromboembolic pulmonary disease.

image Nuclear imaging

image Radionuclide ventriculography and radionuclide angiography (gated blood pool scan) may determine ejection fraction of each ventricle noninvasively.

Echocardiographic findings include the following:

image Transthoracic and transesophageal two-dimensional echocardiography (TTE and TEE, respectively) can be used to evaluate ventricular size and function, valvular dysfunction, and pulmonary hypertension.

image Right ventricular myocardial thickness and dilation.
image Paradoxical leftward motion and flattening of the interventricular septum during both systole and diastole.
image In severe cases, the interventricular septum may bulge into the left ventricle during the entire cardiac cycle, resulting in reduced left ventricular filling and output.

image Doppler echocardiography is used to estimate PA pressure noninvasively.

image The pressure difference between the right ventricle and right atrium can be calculated from the tricuspid valve regurgitant jet usually present in pulmonary hypertension.
image The right atrial pressure needs to be estimated by the size and respiratory variation of flow in the inferior or superior vena cava. The PA pressure is then calculated by the modified Bernoulli equation:

image

image Other findings associated with cor pulmonale are midsystolic closure of the pulmonic valve and pulmonic insufficiency.

Right-sided heart catheterization remains the gold standard for evaluation and diagnosis of pulmonary hypertension and cor pulmonale. Right-sided heart catheterization allows for precise measurement of pulmonary hemodynamics, including PA and right ventricle pressure, as well as the left ventricular end-diastolic pressure (PA “occlusion” pressure, or wedge pressure). It also allows for the initial assessment of response to treatments.

MRI yields accurate dimensions of the right ventricle, although at this time it does not add a proved benefit to echocardiography.

12 What are the indications for use of echocardiography in the evaluation of cor pulmonale?

Indications for TEE and diagnosis of pulmonary hypertension include the following:

Class I: Conditions for which evidence and/or general agreement of an effective treatment exist

1. Suspected pulmonary hypertension
2. To distinguish cardiac versus noncardiac cause of dyspnea in patients in whom clinical and laboratory clues are ambiguous*
3. To follow the response to treatment of pulmonary hypertension
4. Lung disease with clinical suspicion of cardiac involvement (suspected cor pulmonale)

Class II: Conditions for which conflicting evidence and/or a divergence of opinion exist about the usefulness or efficacy of a procedure or treatment

Class IIa: Evidence or opinion is in favor of efficacy.
Class IIb: Efficacy is less established.
1. Pulmonary emboli and suspected clots in right atrium, ventricle, or large PA branches*
2. Measurement of exercise PA pressure
3. Evaluation of candidates for lung transplantation or other surgical procedure for advanced lung disease*

Class III: Conditions for which evidence and/or general agreement exist that the treatment is not effective and in some cases may be harmful

1. Lung disease without any clinical suspicion of cardiac involvement
2. Reevaluation studies of right ventricular function in patients with chronic obstructive lung disease without a change in clinical status

13 Discuss nonpharmacologic treatment options for patients with cor pulmonale

image Lifestyle modifications. Although data are not available, it seems sensible that promoting a healthy lifestyle that includes moderate aerobic exercise and weight reduction should be beneficial. Strenuous activity should be avoided, and supplemental oxygen may be beneficial during even graded exercise, such as walking.

image Oxygen therapy is considered a mainstay of treatment for patients with COPD. Large controlled trials demonstrate that long-term administration of oxygen improves survival in patients with hypoxemia and COPD. Oxygen therapy decreases pulmonary vascular resistance by diminishing pulmonary vasoconstriction and improves right ventricular stroke volume and cardiac output.

image Phlebotomy may provide symptomatic relief of dyspnea to patients with pronounced polycythemia (hematocrit > 60%). Although less frequently used than in the past, phlebotomy can be considered in patients with polycythemia with acute decompensation.

image Noninvasive ventilation (NIV) is the first line of ventilatory support during exacerbation of COPD, and it is standard therapy for advanced OSA. It is reasonable to infer that by correcting hypoxemia and acidosis, NIV will also decrease PA pressure, ease the forward flow of the right ventricle, and improve stroke volume and cardiac output when right ventricle failure is present. However, no data exist on the outcome benefit of NIV in acute cor pulmonale.

14 What are the pharmacologic therapies for patients with cor pulmonale?

image Diuretics are indicated to manage right ventricle failure and volume overload. No evidence exists of benefit of long-term diuretic therapy in compensated cor pulmonale.

image Vasodilators are a mainstay of pharmacologic therapy of pulmonary hypertension. Vasodilators improve cardiac output by decreasing the afterload to the right ventricle, and their efficacy in cor pulmonale depends on their relative selectivity for the pulmonary circulation. Systemic hypotension, syncope, and myocardial infarction are all possible complications of vasodilator therapy. They are discussed in detail later.

image Anticoagulation with warfarin (Coumadin) is indicated for those patients with cor pulmonale resulting from thromboocclusive pulmonary disease. In addition, and in the absence of the customary contraindications, it has been recommended for pulmonary hypertension associated with a variety of other diseases, such as collagen diseases, human immunodeficiency virus, and congenital left-to-right shunts.

Additional therapies are specifically related to the primary lung disease, including surgical interventions, such as repair of intracardiac defects and lung transplantation.

15 Discuss the different classes of vasodilators used in the treatment of cor pulmonale

Long-term treatment of cor pulmonale includes the following:

image Calcium channel blockers (nifedipine, diltiazem, amlodipine) have been used both in the short term as a test of pulmonary vascular responsiveness and in the long term as therapy.

image Prostacyclins improve hemodynamics, symptoms, and outcome of patients with pulmonary hypertension of diverse etiology. Epoprostenol is administered as a continuous intravenous infusion through indwelling central venous access, and its use is limited to centers with the experience and structure to safely provide this treatment. Iloprost is a prostacyclin analogue that can be administered by inhalation. However, it requires a special nebulizer and six to nine administrations per day. Data on the long-term effect of iloprost therapy are still scarce.

image Endothelin-receptor antagonists such as bosentan have shown significant improvements in symptoms and short-term composite outcomes. One advantage of bosentan is its oral administration. Disadvantages come from its common side effects, including headache, flushing, elevation of liver enzyme levels, dependent edema, and anemia, which may lead to discontinuation of treatment.

image Phosphodiesterase inhibitors such as sildenafil improve exercise capacity but do not prevent clinical worsening over time. In many cases, the starting dose of sildenafil is 20 mg 3 times a day, but in many cases, a dose of 80 mg 3 times a day is needed, with significant systemic side effects.

Vasodilators for acute cor pulmonale include the following:

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator available for a number of indications (often off-label) characterized by acute pulmonary hypertension and hypoxemia. Low doses of inhaled NO rapidly and reproducibly induce PA vasodilation and an increase in PaO2 without systemic hypotension. However, its effect on pulmonary pressure and resistance in adults is modest and short-lived. Hence, the indications for inhaled NO are limited to the following:

image Bridge treatment while other options are worked out and

image Test of reactivity of the pulmonary circulation for chronic vasodilator therapy with other drugs.

Inotropes with vasodilatory properties include the following:

image Dobutamine is the prototype of these agents. Dobutamine is a catecholamine with β1 and β2 adrenergic vascular effects. Dobutamine enhances myocardial contractility and decreases vascular resistance, thus increasing stroke volume and decreasing pulmonary and systemic pressure. The balance of these actions determines the effectiveness of the drug in each individual patient. Ideally, it will decrease PA pressure and increase cardiac output enough to maintain an adequate systemic blood pressure. Its effect is limited by systemic hypotension and tachycardia. An advantage of this drug is that, like all catecholamines, it has a short half-life, and its effect regresses rapidly on discontinuation.

image Milrinone is a phosphodiesterase inhibitor (different class from sildenafil) with hemodynamic actions similar to dobutamine, but longer-lived and possibly more effective (i.e., more inotropy and less arrhythmia). Given its different mechanism of action, milrinone can be added in the short term to catecholamines, such as dobutamine or norepinephrine, and further potentiate their inotropic effect.

16 Is the function of the left ventricle affected in cor pulmonale?

Left ventricular dysfunction can occur as a mechanical consequence of the right ventricle pressure and volume overload. As the right ventricle adapts to a higher afterload, its end-diastolic volume increases, and the cross-sectional shape of the right ventricle changes from a crescent to a sphere, affecting the position and function of the interventricular septum. As the septum impinges onto the left ventricle, the diastolic volume of the left ventricle decreases, and the intracavitary pressure increases. Thus filling of the left ventricle is impaired, stroke volume decreases, and left-sided filling pressure increases, in a fashion similar to the mechanics that are seen in left ventricular hypertrophy of, for example, hypertensive cardiomyopathy or aortic stenosis.

17 Discuss the considerations for ventilator management of patients with cor pulmonale

Goals of mechanical ventilation in patients with pulmonary hypertension and cor pulmonale include the following:

image Maintain adequate PaO2 and PaCO2 to optimize PA vasodilation.

image Avoid excessive intrathoracic pressures, which may decrease venous return and increase afterload to the right ventricle, and consequent decreased filling and output of the left ventricle.

image Limit intrathoracic pressure by controlling the level of mean airway pressure, which can be increased by increasing end-inspiratory pressure, end-expiratory pressure (PEEP, auto-PEEP), and inspiratory time. Careful administration of PEEP in patients with acute respiratory failure may be beneficial when it results in alveolar recruitment and consequent relief of hypoxemia.

Key Points Cor Pulmonaleimage

1. Any process that results in pulmonary hypertension can cause cor pulmonale.

2. COPD and untreated OSA are common causes of cor pulmonale.

3. The presence of cor pulmonale in advanced COPD has a poor 5-year survival rate.

Bibliography

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16 Vizza C.D., Lynch J.P., Ochoa L.L., et al. Right and left ventricular dysfunction in patients with severe pulmonary disease. Chest. 1998;113:576–583.

* TEE is typically indicated when TTE studies are not diagnostic.

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