الرحيم الرحمن الله الرحيم بسم الرحمن الله بسمCor pulmonaleCor pulmonale

ByBy

Prof. Dr. Rasheed Abd El Prof. Dr. Rasheed Abd El KhalekKhalek

M. D.M. D.Head Of Internal Medicine & Intensive Care Head Of Internal Medicine & Intensive Care

DepartmentDepartment

DefinitionsDefinitions

Cor pulmonale is a latin word means ”pulmonary heart” .Cor pulmonale is a latin word means ”pulmonary heart” . The world Health Organizaton in 1963 adopted this The world Health Organizaton in 1963 adopted this

definition of cor pulmonale :” hypertrophy of the right definition of cor pulmonale :” hypertrophy of the right ventricle resulting from diseases affecting the function ventricle resulting from diseases affecting the function and/or structure of the lungs, except when these and/or structure of the lungs, except when these pulmonary alterations are the result of diseases that pulmonary alterations are the result of diseases that primarily affect the left side of the heart , as congenital primarily affect the left side of the heart , as congenital heart diseases”heart diseases”

Cor pulmonale is a disease of the right ventricle Cor pulmonale is a disease of the right ventricle characterized by hypertrophy and dilation that results characterized by hypertrophy and dilation that results from diseases directly affecting the lung parenchyma or from diseases directly affecting the lung parenchyma or lung vasculature. Of note ,right heart failure need not be lung vasculature. Of note ,right heart failure need not be present in cor pulmonale .present in cor pulmonale .

Subtypes Of Cor PulmonaleSubtypes Of Cor Pulmonale Cor pulmonale can be either acute or chronic in Cor pulmonale can be either acute or chronic in

development. development. Acute cor pulmonale is the result of a sudden increase in Acute cor pulmonale is the result of a sudden increase in

right ventricular pressure, as seen in massive pulmonary right ventricular pressure, as seen in massive pulmonary embolism or acute respiratory distress syndrome.embolism or acute respiratory distress syndrome.

Chronic cor pulmonale can be further characterized by Chronic cor pulmonale can be further characterized by hypoxic or vascular obliterans pathophysiology.hypoxic or vascular obliterans pathophysiology.

The most common disease process associated with hypoxic The most common disease process associated with hypoxic subtype is chronic obstructive pulmonary disease (COPD).subtype is chronic obstructive pulmonary disease (COPD).

The most common process associated with obliterans The most common process associated with obliterans subtype is pulmonary thromboembolic disease. subtype is pulmonary thromboembolic disease.

Pathophysiology Pathophysiology Under normal phsyologic conditions, the right ventricle pumps Under normal phsyologic conditions, the right ventricle pumps

against a low-resistance circuit.against a low-resistance circuit. Normal pulmonary vascular resistance is approximately one-tenth Normal pulmonary vascular resistance is approximately one-tenth

the resistance of the systemic arteries.the resistance of the systemic arteries. The right ventricle is thin walled and able to accommodate The right ventricle is thin walled and able to accommodate

considerable changes in volume without large changes in considerable changes in volume without large changes in pressure.pressure.

Increased cardiac output leads to recruitment of underperfused Increased cardiac output leads to recruitment of underperfused pulmonary vessels and distention of other pulmonary vessels.pulmonary vessels and distention of other pulmonary vessels.

The initial pathophysiologic event in the production of cor The initial pathophysiologic event in the production of cor pulmonale is elevation of the pulmonary vascular resistance.pulmonale is elevation of the pulmonary vascular resistance.

As the resistance increases, the pulmonary arterial pressure rises, As the resistance increases, the pulmonary arterial pressure rises, right ventricular work increases, right ventricular hypertrophy right ventricular work increases, right ventricular hypertrophy (i.e.,thickening, dilation, or both ).(i.e.,thickening, dilation, or both ).

Right ventricular failure occurs when compensation through Right ventricular failure occurs when compensation through dilation and hypertrophy are exhausted.dilation and hypertrophy are exhausted.

CausesCauses

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

Pulmonary hypertension is defined as Pulmonary hypertension is defined as mean pulmonary artery pressure mean pulmonary artery pressure >20 mmHg at rest>20 mmHg at rest or >30 mmHg or >30 mmHg with exercise.with exercise.

Pathophysiology of pulmonary Pathophysiology of pulmonary hypertensionhypertension

1.1. Hypoxic pulmonary vasoconstriction and Hypoxic pulmonary vasoconstriction and arterial occlusion are the major causes of arterial occlusion are the major causes of pulmonary hypertension.pulmonary hypertension.

2.2. Both produce reduced blood flow with Both produce reduced blood flow with increased vascular resistance.increased vascular resistance.

3.3. Acute hypoxic pulmonary vaso –Acute hypoxic pulmonary vaso –constriction optimizes ventilation – constriction optimizes ventilation – perfusion relationships when regional perfusion relationships when regional ventilation demands in the lung are not ventilation demands in the lung are not met. met.

4.4. However, chronic hypoxemia However, chronic hypoxemia leading to chronic vasoconstriction leading to chronic vasoconstriction produces smooth ms proliferation in produces smooth ms proliferation in small pulmonary arteries.small pulmonary arteries.

5.5. Decreased luminal cross sectional Decreased luminal cross sectional diameter leads to increased diameter leads to increased resistance and increased pulmonary resistance and increased pulmonary artery pressure.artery pressure.

6.6. These architectural changes in These architectural changes in pulmonary arteries may promote pulmonary arteries may promote platelet aggregation and activation.platelet aggregation and activation.

7.7. This leads to thrombi formation that This leads to thrombi formation that further increases pulmonary further increases pulmonary vascular resistance and pulmonary vascular resistance and pulmonary hypertension.hypertension.

8.8. Hypoxemia produces changes in Hypoxemia produces changes in vascular mediators such as Nitric vascular mediators such as Nitric Oxide, Endothelin1 (ET1) and platelet Oxide, Endothelin1 (ET1) and platelet derived growth factors (PDGf A and B).derived growth factors (PDGf A and B).

9.9. Nitric oxide is a vasodilator; Nitric oxide is a vasodilator; hypoxemia reduces endothelial cell hypoxemia reduces endothelial cell production of nitric oxide and results production of nitric oxide and results in impaired smooth ms relaxation.in impaired smooth ms relaxation.

10.10. Hypoxemia increases ET1 Hypoxemia increases ET1 production and PDGF A and B .production and PDGF A and B .

11.11. ET1 is apotent vasoconstrictor, and ET1 is apotent vasoconstrictor, and PDGF A and B results in pulmonary PDGF A and B results in pulmonary vascular remodeling.vascular remodeling.

12.12. All causes increased pulmonary All causes increased pulmonary artery resistance and causes artery resistance and causes pulmonary hypertension.pulmonary hypertension.

PresentationPresentation

The signs and symptoms of cor The signs and symptoms of cor pulmonale are often subtle unless the pulmonale are often subtle unless the disease process becomes far advanced.disease process becomes far advanced.

In addition, clinicians tend to focus on In addition, clinicians tend to focus on the disease giving rise to cor pulmonale the disease giving rise to cor pulmonale rather than on cor pulmonale itself.rather than on cor pulmonale itself.

Manifestations of cor pulmonale are Manifestations of cor pulmonale are similar to those of right side heart similar to those of right side heart failure. failure.

Symptoms of Cor Symptoms of Cor PulmonalePulmonale::

FatigabilityFatigability Dyspnea on exertionDyspnea on exertion SyncopeSyncope Chest painChest pain PalpitationPalpitation Abdominal edema or distensionAbdominal edema or distension Lower extremity edemaLower extremity edema

Clinical Signs Of Cor Clinical Signs Of Cor PulmonalePulmonale::

Accentuated A wave of the jugular Accentuated A wave of the jugular venous pulsationsvenous pulsations

Prominent jugular V wave, indicating Prominent jugular V wave, indicating the presence of tricuspid regurgitationthe presence of tricuspid regurgitation

Palpable left parasternal liftPalpable left parasternal lift Accentuated pulmonic component of Accentuated pulmonic component of

the second heart soundthe second heart sound Right sided S4 heart soundRight sided S4 heart sound

Murmurs of tricuspid and pulmonic Murmurs of tricuspid and pulmonic insufficiencyinsufficiency

Dependent prepheral edema and Dependent prepheral edema and hepatomegalyhepatomegaly

The mortality associated with The mortality associated with cor pulmonalecor pulmonale

Patients with COPD have a 60% 5-year Patients with COPD have a 60% 5-year survival rate, whereas patients with COPD survival rate, whereas patients with COPD and pulmonary artery pressure in excessof and pulmonary artery pressure in excessof 25 mmHg have a survival of only 36%.25 mmHg have a survival of only 36%.

The 5-year survival rate for patients with The 5-year survival rate for patients with COPD who develop preipheral edema is COPD who develop preipheral edema is approximately 30%.approximately 30%.

It is unclear whether pulmonary artery It is unclear whether pulmonary artery hypertension is the cause of death or hypertension is the cause of death or whether it is a marker of increased whether it is a marker of increased motality.motality.

Electrocardiography criteria of Electrocardiography criteria of right ventricular hypertrophyright ventricular hypertrophy

Right axis deviation.Right axis deviation. P pulmonale (large P wave ) in the P pulmonale (large P wave ) in the

inferior and anterior leads “ right inferior and anterior leads “ right atrial enlargement “.atrial enlargement “.

Right bundle branch block.Right bundle branch block. Right precordial T-wave inversions.Right precordial T-wave inversions. Delayed interinsicoid deflection of Delayed interinsicoid deflection of

right precordial leads. right precordial leads.

E.C.G criteria of R.V.HE.C.G criteria of R.V.H

SS11 Q Q33 T T33 pattern. pattern. QR pattern in lead VQR pattern in lead V11 or V or V33R.R. An R wave in VAn R wave in V11 or V or V33R.R. An R/S ratio >1 in VAn R/S ratio >1 in V11 or <1 in V or <1 in V55 or or

VV66..

SS11 Q Q33 T T33 Pattern Pattern

Investigations Help In Investigations Help In DiagnosisDiagnosis

Chest Radiograph:Chest Radiograph:1.1. Enlarged pulmonary artery.Enlarged pulmonary artery.2.2. Enlarged right ventricle.Enlarged right ventricle.3.3. Distended azygous or other central vein.Distended azygous or other central vein.4.4. Westermark sign “oligemia of lung lobe Westermark sign “oligemia of lung lobe

or entire lung “.or entire lung “.5.5. Hampton’s hump “wedge shaped opacityHampton’s hump “wedge shaped opacity6.6. COPD signs as anterior-posterior COPD signs as anterior-posterior

diameter , flattening of diaphragm , diameter , flattening of diaphragm , honeycombing and hyperlucency.honeycombing and hyperlucency.

Computed tomography:Computed tomography:1.1. Main pulmonary artery diameter Main pulmonary artery diameter

measurements >29 mm have a measurements >29 mm have a sensitivity of 84 % and specificity of sensitivity of 84 % and specificity of 75% for the diagnosis75% for the diagnosis of pulmonary of pulmonary hypertension.hypertension.

2.2. There are data to suggest that an There are data to suggest that an enlarged main pulmonary artery enlarged main pulmonary artery diameter and ratio of segmental diameter and ratio of segmental pulmonary artery diameter to pulmonary artery diameter to corresponding bronchus diameter > corresponding bronchus diameter > 1 increases the specificity of a 1 increases the specificity of a pulmonary hypertension diagnosis.pulmonary hypertension diagnosis.

Echocardiography :Echocardiography :1.1. An adequate examination is reported in An adequate examination is reported in

up to 65 – 80 % of patients with COPD up to 65 – 80 % of patients with COPD because of the technical difficulty because of the technical difficulty associated with hyperinflation.associated with hyperinflation.

2.2. A better examination can be obtained A better examination can be obtained with transesophageal with transesophageal echocardiography.echocardiography.

3.3. Doppler echocardiography has aided in Doppler echocardiography has aided in the assessment of pulmonary artery the assessment of pulmonary artery pressure by measuring the flow of pressure by measuring the flow of regurgitant blood across the tricuspid regurgitant blood across the tricuspid valave or by measuring right vetricular valave or by measuring right vetricular ejection flow. ejection flow.

Right heart catheterization :Right heart catheterization :

1.1. This is the gold standard for thorough This is the gold standard for thorough evaluation and diagnosis of pulmonary evaluation and diagnosis of pulmonary hypertension.hypertension.

Radionuclide angiography (gated Radionuclide angiography (gated blood pool scan ):blood pool scan ):

1.1. This test is most useful for measuring This test is most useful for measuring right and left ventricular ejection right and left ventricular ejection fraction.fraction.

Magnetic resonance imaging :Magnetic resonance imaging :

1.1. This non invasive technique yields highly This non invasive technique yields highly accurate dimensions of the right accurate dimensions of the right ventricle.ventricle.

TreatmentTreatment

Non pharmacological treatment :Non pharmacological treatment :1.1. Oxygen therapy.Oxygen therapy.2.2. Phlebotomy.Phlebotomy.3.3. Non invasive positive pressure Non invasive positive pressure

ventilation (NIPPV).ventilation (NIPPV). Pharmacological treatment :Pharmacological treatment :1.1. Diuretics .Diuretics .2.2. Anticoagulation .Anticoagulation .3.3. Vasodilators . Vasodilators .

Oxygen therapyOxygen therapy

This is considered a mainstay of treatment This is considered a mainstay of treatment for patients with COPD .for patients with COPD .

Large controlled trials demonstrate that Large controlled trials demonstrate that long term administration of oxygen long term administration of oxygen improves survival in hypoxemic patients improves survival in hypoxemic patients with COPD.with COPD.

Oxygen therapy decreases pulmonary Oxygen therapy decreases pulmonary vascular resistance by diminishing vascular resistance by diminishing pulmonary vasoconstriction and improves pulmonary vasoconstriction and improves right ventricular stroke volume and right ventricular stroke volume and cardiac output .cardiac output .

PhlebotomyPhlebotomy In patient with pronounced polycythemia In patient with pronounced polycythemia

(hematocrit >60 % ), phlebotomy may (hematocrit >60 % ), phlebotomy may provide symptomatic relief .provide symptomatic relief .

In resting patients , phlebotomy can affect a In resting patients , phlebotomy can affect a mild decrease in pulmonary artery pressure mild decrease in pulmonary artery pressure and pulmonary vascular resistance .and pulmonary vascular resistance .

In general , blood viscosity has less effect In general , blood viscosity has less effect than blood volume on pulmonary arterial than blood volume on pulmonary arterial pressure .pressure .

Phlebotomy , with a goal hematocrit of 50 Phlebotomy , with a goal hematocrit of 50 %, may improve exercise tolerance in %, may improve exercise tolerance in patients with polycythemic COPD.patients with polycythemic COPD.

Phlebotomy is not an optimal single Phlebotomy is not an optimal single therapy but can be considered in therapy but can be considered in polycythemic patients with acute polycythemic patients with acute decompensation .decompensation .

Noninvasive positive pressure Noninvasive positive pressure ventilation ( NIPPV )ventilation ( NIPPV )

For patients with acute COPD For patients with acute COPD exacerbations, NIPPV has been exacerbations, NIPPV has been shown to improve outcomes in acute shown to improve outcomes in acute hospitalization.hospitalization.

No such data exist for long-term No such data exist for long-term treatment of COPD or sleep-treatment of COPD or sleep-disordered breathing with NIPPV.disordered breathing with NIPPV.

There is evidence that oxygenation is There is evidence that oxygenation is improved in these patients, but improved in these patients, but reduction in pulmonary artery reduction in pulmonary artery pressure is only anecdotal. pressure is only anecdotal.

DiureticsDiuretics Diuretic therapy with salt restricted Diuretic therapy with salt restricted

diet may be needed in congestive diet may be needed in congestive heart failure to take care of the heart failure to take care of the excessive water that the lungs share excessive water that the lungs share and to improve alveolar ventilation and and to improve alveolar ventilation and gas exchange.gas exchange.

However, the use of diuretics may However, the use of diuretics may produce hemodynamic adverse effects, produce hemodynamic adverse effects, such as volume depletion, decrease such as volume depletion, decrease venous return to the right ventricle, venous return to the right ventricle, and decreased cardiac output.and decreased cardiac output.

Another complication is the Another complication is the production of hypokalemic metabolic production of hypokalemic metabolic alkalosis, which diminishes the Coalkalosis, which diminishes the Co22 stimulus to the respiratory center, stimulus to the respiratory center, decreasing ventilatory drive.decreasing ventilatory drive.

AnticoagulationAnticoagulation

Chronic anticoagulation with Chronic anticoagulation with Warfarin may provide benefit for Warfarin may provide benefit for those patients with Cor Pulmonale those patients with Cor Pulmonale resulting from thrombo-occlusive resulting from thrombo-occlusive pulmonary disease.pulmonary disease.

vasodilatorsvasodilators Vasodilators improve cardiac output Vasodilators improve cardiac output

in many patients with cor pulmonale.in many patients with cor pulmonale. However, treatment with vasodilators However, treatment with vasodilators

may be associated with adverse may be associated with adverse effects, including systemic effects, including systemic hypotension that coronary perfusion hypotension that coronary perfusion pressure, blunting of hypoxic pressure, blunting of hypoxic pulmonary vasoconstriction and pulmonary vasoconstriction and circulatory collapse.circulatory collapse.

Different classes of Different classes of vasodilators used in Cor vasodilators used in Cor

PulmonalePulmonale Nonspecific vasodilators:Nonspecific vasodilators:1.1. Hydralazine increases cardiac output Hydralazine increases cardiac output

in patients with COPD; however, its in patients with COPD; however, its ability to decrease pulmonary artery ability to decrease pulmonary artery pressure is unpredictable.pressure is unpredictable.

2.2. Nitroprusside may provide benefit but Nitroprusside may provide benefit but also runs the risk of systemic also runs the risk of systemic hypotension and compromise of hypotension and compromise of adequate coronary perfusion pressure. adequate coronary perfusion pressure.

3.3. Calcium channel blockers such as Calcium channel blockers such as Nifedipine reduce pulmonary Nifedipine reduce pulmonary vascular resistance and increase vascular resistance and increase cardiac output only for the short cardiac output only for the short term.term.

4.4. Verapamil and Diltiazem have not Verapamil and Diltiazem have not proved effective in dilating proved effective in dilating pulmonary vasculature.pulmonary vasculature.

Pulmonary vasodilators :Pulmonary vasodilators :

1.1. Prostaglandins decrease pulmonary Prostaglandins decrease pulmonary artery pressure and increase right artery pressure and increase right ventricular ejection fraction and ventricular ejection fraction and cardiac output.cardiac output.

2.2. Aerosolized prostacyclin causes Aerosolized prostacyclin causes pulmonary artery vasodilatation pulmonary artery vasodilatation and improves cardiac output and and improves cardiac output and arterial oxyhemoglobin saturation in arterial oxyhemoglobin saturation in patients with chronic pulmonary patients with chronic pulmonary hypertension.hypertension.

3.3. Nitric oxide provides a real clinical Nitric oxide provides a real clinical scenario. It reliably decreases scenario. It reliably decreases pulmonary vascular resistance pulmonary vascular resistance without causing systemic hypotension without causing systemic hypotension and preserves or improves optimal and preserves or improves optimal ventilation-perfusion match. Its ventilation-perfusion match. Its drawbacks are difficult drawbacks are difficult administration, high cost, and a well-administration, high cost, and a well-documented tachyphylactic effect. documented tachyphylactic effect. Multiple studies have shown that its Multiple studies have shown that its benefits are most significant for only benefits are most significant for only 1-3 days, especially in patients with 1-3 days, especially in patients with acute respiratory distress syndrome. acute respiratory distress syndrome.

Inotropes with vasodilatory Inotropes with vasodilatory properties :properties :

1.1. Dobutamine is an inotropic agent Dobutamine is an inotropic agent with vasodilatory effect which with vasodilatory effect which improves right ventricular function improves right ventricular function and cardiac output, but its effect on and cardiac output, but its effect on systemic blood pressure is systemic blood pressure is unpredictable.unpredictable.

2.2. Amrinone lowers pulmonary artery Amrinone lowers pulmonary artery pressure and rises cardiac output pressure and rises cardiac output and systemic blood pressure.and systemic blood pressure.

Endothelin receptor Endothelin receptor antagonist :antagonist :

1.1. Bosentan is an endothelin receptor Bosentan is an endothelin receptor antagonist that produces antagonist that produces pulmonary vasodilation and pulmonary vasodilation and attenuates ventricular remodeling attenuates ventricular remodeling and improve survival on chronic and improve survival on chronic use.use.

Role of digoxin in treatmentRole of digoxin in treatment

Cardiac output improves in about 10% Cardiac output improves in about 10% of patients with primary pulmonary of patients with primary pulmonary hypertension who receive digoxin.hypertension who receive digoxin.

This rate is similar to that in patient This rate is similar to that in patient with left ventricular dyfunction.with left ventricular dyfunction.

Patients who receive digoxin also show Patients who receive digoxin also show a modest increase in pulmonary a modest increase in pulmonary pressure, perhaps due to increase in pressure, perhaps due to increase in cardiac output.cardiac output.

Clinical studies show improvement in Clinical studies show improvement in right ventricular function only in right ventricular function only in those patients who have reduced left those patients who have reduced left ventricular ejection fraction.ventricular ejection fraction.

Recently, digoxin has fallen out of Recently, digoxin has fallen out of favor in the setting of left ventricular favor in the setting of left ventricular dysfunction; the trend in clinical dysfunction; the trend in clinical medicine has been its continued use medicine has been its continued use in rate control.in rate control.

KEY POINTS OF COR KEY POINTS OF COR PULMONALEPULMONALE

Right side heart failure is not necessary to Right side heart failure is not necessary to make the diagnosis of cor pulmonale.make the diagnosis of cor pulmonale.

Any process that cause pulmonary Any process that cause pulmonary hypertension can cause cor pulmonale.hypertension can cause cor pulmonale.

COPD is the most common cause of COPD is the most common cause of chronic cor pulmonale.chronic cor pulmonale.

Cor pulmonale is common in advanced Cor pulmonale is common in advanced obstructive lung disease and has a poor 5-obstructive lung disease and has a poor 5-year survival rate.year survival rate.

Ventricular interdependence can developin Ventricular interdependence can developin late stages of cor pulmonale.late stages of cor pulmonale.

PRAISE BE TO PRAISE BE TO ALLAAH ALLAAH

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