The Cardiac Story


The Common Vein Copyright 2008

Daniela Budiu MD


The purpose of this article is to review dyspnea of cardiac etiology and the pathophysiology of acute cardiogenic pulmonary edema which is the  major mechanism of cardiac dyspnea. We are also going to review pulmonary embolism, pleural and pericardial effusion as other important causes of cardiac dypnea. Ischemia and tachyarrythmia can lead to development of  dyspnea and  pulmonary edema but they are not the purpose of this review.


Definition and terminology

Dyspnea represents a cardinal symptom in patients with cardiopulmonary disease. It can be defined as difficult, labored and unpleasant breathing or uncomfortable awareness of breathing or need to breath that is out of proportion to the patient’s level of physical activity. (Roland H. Ingram Jr). It can be provoked by excessive activation of respiratory centers in the brainstem by stimuli from mechanoreceptors in the lung, respiratory muscles, airways, chemoreceptors in the brain and vascular receptors.

Under normal circumstances, a resting person is not aware of the act of breathing. Temporary during exercise we may become conscious of our breathing but no discomfort should be experienced. Even if there is unpleasant sensation of breathing with a strenuous exercise, the sensation is transitory and seems appropriate for the level of exercise. Central and peripheral mechanisms that control breathing are involved in adjusting the ventilation to the increased demand metabolic as seen with physical activity or other conditions as fear, anxiety, etc.

Patients use different words to describe the sensation of dyspnea such as “cannot get enough air”, “hard to breath”, “air doesn’t go all the way down”, “choking sensation”, “tightness in the chest”. The verbal descriptors may correlate with the degree of dyspnea but they are not always helpful with differentiating between the cardiac and pulmonary causes of dyspnea.

Multiple studies were done to determine the differences between the terms used by chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) patients to report dyspnea. Patients with COPD reported dyspnea as “ hard to breath” , “ scary feeling”, “shortness of breath”, “cannot get enough air” or “my breath doesn’t go out all the way”. Patients with CHF used terms as “shortness of breath”, “gasping” and “ cannot get enough air”. In conclusion, COPD and CHF patients share common words to express their breathing discomfort and once it is established that a patient has dyspnea, it is of crucial importance to determine the cause, the circumstances in which occur and to assess the associated symptoms.

Dyspnea can occur with physical exertion and also at rest. Exertional dyspnea can be quantified based on the amount of physical activity required to produce the sensation. In assessing the severity of dyspnea it is important to know the overall functional status of the patient. In an active and physically trained person development of dyspnea after running a certain distance could be as significant as occurrence of dyspnea on a sedentary patient upon walking a much smaller distance. The usual questions to assess the degree of dyspnea on exertion (DOE) are “how much can you walk on a ground level without experiencing shortness of breath?”  or “ how many flights of stairs can you climb without feeling short of breath or need to stop?” Dyspnea is a subjective perception and there is interindividual variation in perception and reporting of dyspnea. Some patients with severe disease may only report mild dyspnea and on the other hand patients with mild disease may experience severe shortness of breath. Patients with very limited physical activity due to different comorbidities (severe arthritis, peripheral vascular disease etc) may not even report exertional dyspnea at all as they are mostly bedbound.

Dyspnea at rest can occur with certain conditions as pulmonary embolism, spontaneous pneumotorax, acute ischemic event, anxiety etc. A good history taking with attention paid to associated symptoms, comorbidities, age of the patient, circumstances of the dyspnea and physical exam along with other diagnostic tools will lead to the correct identification of the cause of dyspnea in most of the cases and proper treatment.

Dyspnea can be the manifestation of an acute event with a sudden onset in a patient without any chronic baseline dyspnea (pulmonary emboli, pneumotorax, angioedema, aspiration of a foreign body or food, acute cardiac ischemia etc)orit can represent a decompensation of a chronic disease with an otherwise less symptomatic or more compensated clinical course (acute exacerbation in a patient with known COPD or asthma, acute decompensation in a patient with known compensated heart failure, worsening of pleural or pericardial effusions etc).

The most used classification of dyspnea is based on its etiology with the major distinction being between cardiac and pulmonary dyspnea.

Dyspnea of a pulmonary etiology can be secondary to diseases that affect any of the following lung structures: airways, lung parenchyma, pulmonary vessels, chest wall ad respiratory muscles. Acute obstruction of the extrathoracic upper airways can be seen with food or foreign body aspiration or an allergic reaction with angioedema .More chronic upper airway obstruction can be due to a tumor or fibrotic stenosis after a prolonged intubation. Tracheomalacia, a congenital or acquired condition, is caused by increased softening of the tracheal cartilages and leads to dyspnea due to inspiratory collapse of trachea. Obstructive disease of the intrathoracic airways as chronic bronchitis, asthma, bronchiectasis also cause dyspnea.

Any process that affects lung parenchyma can cause dyspnea. This pathology ranges from an acute pneumonia to more chronic processes as sarcoidosis, emphysema, interstitial lung disease etc.

In pulmonary vascular occlusive disease there is obstruction of the pulmonary blood vessels by emboli which interfere with the capillary alveolar gas exchange and cause the perception of dyspnea. This process can be acute when a big blood clot occludes a main pulmonary artery or a more chronic process when multiple small emboli obstructs more peripheral blood vessels.

Diseases of chest wall and respiratory muscle represent another important category of diseases that cause dyspnea. Weakness and paralysis of respiratory muscle due to congenital or acquired neurological and muscular disorders frequently leads to dyspnea and respiratory failure. Also chest wall deformities as seen with severe kyphoscoliosis, pectus excavatum etc interfere with normal ventilation and cause dyspnea.

The pathophysiological mechanisms of pulmonary causes of dyspnea are subject of a different review (see pulmonary causes of dyspnea).

Cardiac Dyspnea

Dyspnea and angina represent two major symptoms of cardiac disease. Dyspnea may serve as an anginal equivalent and a marker of underlying cardiovascular disease even in the absence of chest pain.(Marwick 2005)

Dyspnea can be a symptom in both acute and chronic cardiac disease. Acute dyspnea of cardiac etiology can occur with myocardial infarction, cardiac tamponade, acute failure of left ventricle, acute valvular disease (acute mitral regurgitation or aortic regurgitation), disturbances of the heart rhythm or an embolus  (a clump of tissue, fat or gas) that is blocking the  pulmonary circulation.All the conditions enumerated above can lead to development of acute pulmonary edema which represents the pathophysiological substrate of acute cardiac dyspnea. The underlying mechanism of acute pulmonary edema will be reviewed below.

Dyspnea can also be a more chronic symptom of different cardiac diseases as seen with ischemia without myocardial infarction, systolic and diastolic heart failure, chronic valvular disease (mitral regurgitation, mitral stenosis, aortic stenosis) or pericardial effusion without tamponade. These conditions are associated with variable degree of dyspnea on their compensated states, however they can evolve into acute dyspnea and acute pulmonary edema under different circumstances.

Cardiac dyspnea has a wide spectrum of clinical manifestations, ranging from dyspnea on exertion (DOE), orthopnea to paroxysmal nocturnal dyspnea and acute pulmonary edema.

Orthopnea is the term used to describe dyspnea that occurs in the supine position, in other words, patient cannot lye flat due to difficulty breathing. It is quantified by the number of pillows that the patient uses to sleep on to keep a more upright position and to improve breathing. It is mainly a characteristic of congestive heart failure but can also occur is some patients with asthma and chronic obstruction of airways and in patients with bilateral diaphragmatic paralysis.  Patients with severe left ventricular failure report having episodes of paroxysmal nocturnal dyspnea (PND) also known as cardiac asthmaThis condition ischaracterized byattacks of severe shortness of breath  during sleep that leads to awakening of the patient “gasping for air”. Platypnea is the opposite term of orthopnea and defines dyspnea that occurs only in upright position. It is mostly seen in patients with an interatrial communication (atrial septal defect, patent foramen ovale) and  shunt of the blood from right to left upon assuming an upright position.

Trepopnea refers to the dyspnea that occurs in a lateral decubitus position and is most often seen in patients with heart failure.

Mechanisms of cardiac dyspnea(Ware and Matthay 2005)

The major mechanism of dyspnea in patients with heart disease is elevation of pulmonary capillary pressure which leads to transudation of fluid initially into the interstitial space followed by transudation into the alveolar space. The pulmonary interstitium extends from the space adjacent to blood capillaries and alveoli (perimicrovascular interstitium) to the loose connective tissue around bronchi and large blood vessels (peribronchovascular interstitium).In the normal lung fluid moves continuously from the capillary bed to the pulmonary interstitial space. The fluid leakage occurs trough small gaps between capillary endothelial cells. Once the filtered fluid enters the interstitial space, most of it is removed by the lymphatics and returns back to systemic circulation. Normally the fluid filtered into the interstitial space doesn’t enter the alveoli as the alveolar epithelium has very tight junctions.  According to Starling equation filtration of a fluid across a membrane depends on the permeability of the respective membrane and the equilibrium between the hydrostatic and osmotic pressure on both sides of the membrane. The hydrostatic pressure pushes the fluid trough the membrane and the osmotic pressure tries to offset the hydrostatic pressure holding the fluid in that compartment. If we apply the Starling equation to the lung, the flow of fluid between the capillary bed and the interstitial space depends on the permeability of the capillary membrane, hydrostatic and protein osmotic capillary pressure as well as hydrostatic and protein osmotic interstitial pressure. When the hydrostatic pressure in the pulmonary capillary exceeds the interstitial hydrostatic pressure the rate and amount of fluid that traverses the capillary endothelium into the interstitial space increases. With further increase in the hydrostatic pulmonary microcirculation pressure the filtered fluid will break through the alveolar epithelium flooding the alveoli causing the cardiogenic pulmonary edema. Similarly, when the interstitial pressure in the lungs exceeds the pleural interstitial pressure the fluid will move into the pleural space causing pleural effusions. Since the permeability of the capillary endothelium is normal, the filtered fluid has a low protein content (transudate). Transudation of the fluid into the interstitial space stiffens the lungs and reduces their compliance. It also stimulates juxtacapillary receptors in the alveolar interstitial space. Chronically elevated pulmonary venous and capillary pressure causes thickening of the walls of the small pulmonary vessels and increase in perivascular cells and fibrous tissue with further reduction in compliance. Presence of interstitial fluid will compromise the lumen of the small airways as the interstitial space becomes more crowded. The combination of decrease lung compliance and increase airways resistance due to luminal narrowing will augment the effort of breathing causing the subjective experience of dyspnea.

Orthopnea i.e. dyspnea when lying flat is due to alteration of gravitational forces when this position is assumed with subsequent elevation of pulmonary venous and capillary pressure. It is due to increased blood volume in the supine position as the gravitational pooling of blood in the lower extremities seen with standing position is no longer into effect. A diseased left ventricle is not able to accommodate this increased blood volume leading to increasing filling pressures. Paroxysmal nocturnal dyspnea (PND) occurs usually in patients with already elevated pulmonary pressures. Is it triggered by an increase in the total blood volume at night due to reabsorption of edema from dependent portions of the body. During sleep a person can tolerate relatively higher pressure of pulmonary capillary bed and they will wake up with a feeling of suffocation and wheezing when pulmonary edema and bronchospasm have already developed. The PND is also called “cardiac asthma” and must be differentiated from a true asthma attack and chronic bronchitis.

Removal of the fluid from the air spaces of the lungs depends on active transport of sodium and chloride across the alveolar membrane. The extent of alveolar flooding depends on the degree of the interstitial edema, the integrity of alveolar epithelium and its ability to actively remove the alveolar edema fluid. The resolution of cardiogenic pulmonary edema is usually rapid with decreasing the hydrostatic pressure as the integrity of microvascular membrane is intact.

In conclusion the hallmark of cardiogenic pulmonary edema or so called volume overload edema is an acute rise in the hydrostatic capillary pressure leading to interstitial and alveolar fluid accumulation. The increase in pulmonary capillary pressure is mainly caused by left ventricular dysfunction, systolic or diastolic, or valvular disease. With left ventricular systolic failure the pump function of the left ventricle is affected whereas with diastolic dysfunction there is abnormal filling of the left ventricle during diastole. Both systolic and diastolic dysfunctions lead to elevated left ventricular pressure during end diastole. This leads in turn to elevated left atrial pressure due to higher resistance encountered by atria during their emptying into the ventricles. Higher atrial pressure will reflect into higher pulmonary veins pressure with subsequent higher pulmonary capillary bed pressure. Mild elevation of the left atrial pressure to 18-25 mm Hg causes edema in the perimicrovascular and peribronchovascular interstitial space. With further increase of the left atrial pressure above 25 mm Hg the filtered fluid will flood the alveoli. Common causes of cardiogenic pulmonary edema are ischemia with or without myocardial infarction, aortic or mitral valve disease and exacerbation of systolic of diastolic dysfunction.

The entity known as non cardiogenic pulmonary edema is also being characterized by alveolar flooding however it has a different mechanism. Direct or indirect lung injury causes increase in the permeability of the microvascular  endothelial membrane with major leakage of fluid and protein in the alveoli. The epithelial alveolar membrane is also injured.  Noncardiogenic pulmonary edema has a high protein content due the injured endothelial membrane which is more permeable to larger molecules such as plasma proteins. The resolution of noncardiogenic pulmonary edema is more delayed as the injured alveolar epithelium has a decrease capacity to remove the alveolar fluid. Non cardiogenic pulmonary edema is associated with sepsis, pneumonia, severe pancreatitis, aspiration of gastric content and blood transfusion.

Clinical evaluation of a patient with pulmonary edema

Patients with cardiogenic pulmonary edema mainly complain of dyspnea. Also they can present with cough with expectoration of frotty edema fluid due to alveolar flooding. A classic history of PND or orthopnea suggest cardiac etiology as cause of dyspnea dyspnea.

Keep in mind that cardiogenic and noncardiogenic pulmonary edema may present similarly and the main focus of the initial clinical evaluation should be identifiying the underlying condition that lead to pulmonary edema. Dyspnea associated with chest pain may prompt ischemia and an acute coronary event as the cause of pulmonary edema. However, lack of chest pain doesn’t exclude ischemia as the cause of pulmonary edema as diabetic patients can experience silent myocardial infarction leading to acute pulmonary edema.

In contrast, acute dyspnea in the setting of sepsis, pneumonia, trauma, blood transfusions, vomiting with gastric content aspiration can serve as clinical clues for non cadiogenic pulmonary edema. Unfortunately in some clinical circumstances it is impossible to distinguish cardiogenic from noncardiogenic pulmonary edema by history only. For example, in a patient with cardiac arrest or syncope due to massive myocardial infarction, development of pulmonary edema can be secondary to the initial cardiac event   (cardiogenic pulmonary edema) and possible aspiration of gastric content due to loss of consciousness ( noncardiogenic pulmonary edema).  Similarly, in patients with massive trauma, the initial noncardiogenic pulmonary edema can be complicated by a component of cardiogenic pulmonary edema in the setting of aggressive fluid resuscitations and massive fluid overload.

On the physical exam patient with pulmonary edema are tachypneic (i. e increased respiratory rate) and hypoxemic (decreased oxygen saturation on pulse oxymetry). The heart rate can  be tachycardic ( above 100 beats  per minute) of severely bradycardic ( 30 beats per minute).The blood pressure is usually low once the patient are in a shock state (systolic blood pressure < 90 mm Hg).The cardiac examination is abnormal in a patient with cardiogenic pulmonary edema. Presence of a S3 gallop (an extrasound during early diastole after the second cardiac sound) is relative specific for cardiogenic pulmonary edema. A systolic or diastolic murmur should also raise suspicion for cardiogenic pulmonary edema due to a severely stenotic or leaky valve. Engorged neck vein, enlarged liver and swelling of the lower extremities are signs of elevated central venous pressure due to heart failure. They are not specific for heart failure only as they can be seen in fluid overload due to hepatic or kidney failure.

Lung auscultation in a patient with pulmonary edema will reveal inspiratory crackles, sometimes wheezing and rhonchi. This is the least specific for the etiology of the pulmonary edema since the auscultatory findings reflect the alveolar flooding which is common in both cardiogenic and noncardiogenic edema. The remaining of physical examination is very important in a patient with a patient with acute dyspnea and possible pulmonary edema and sometimes can help with distinction between cardiac and noncardiac etiology. A`distended, tender abdomen without any bowel sounds in a patient  with acute dyspnea can suggest a perforated viscus  that lead to  acute lung injury and noncardiogenic pulmonary edema. The extremities in a patient with noncardiogenic pulmonary edema are usually warmer whereas in cardiogenic edema they are cold and cyanotic reflecting poor cardiac output.

Laboratory testing

An EKG should be done within five minutes from the initial presentation of a patient with acute dyspnea and it may reveal myocardial ischemia or infarction. Elevated cardiac enzymes including troponins suggest cardiac damage but some leak of cardiac enzymes can also occur is septic patients or in patients with pulmonary embolism. Plasma level of brain natriuretic peptide (BNP) is elevated in patients with cardiogenic pulmonary edema. BNP is produced by the cardyomyocites in the left ventricle in response to  elevated intracardiac pressures and increased wall stretch. A level below 100 pg/ml excludes heart failure as the etiology of the pulmonary edema and  a level above 500 pg/ml makes the heart failure more likely etiology of dyspnea. An intermediate BNP level between 100 and 500 pg/ml doesn’t distinguish reliably cardiogenic from noncardiognic pulmonary edema. BNP is also elevated in patients with kidney failure and a level of 200 pg/ml has been suggested as a cutoff value to rule out heart failure as the etiology of pulmonary edema. BNP is also secreted by cardyomyocites of the right ventricle when the right ventricle pressure is elevated as seen with acute pulmonary embolism, pulmonary hypertension and cor pulmonale.

In a patient with mental status change and signs of pulmonary edema a toxic serum screen should be done as intoxications can also cause acute lung injury and noncardiogenic pulmonary edema. Elevated pancreatic enzymes in patient with abdominal pain and dyspnea may suggest acute pancreatitis as the etiology of the noncardiogenic pulmonary edema. Lactic acid level is not really helpful in differentiating the two entities of pulmonary edema. Lactic acid level is an indicator of anaerobic tissue metabolism. It can be elevated in cardiogenic pulmonary edema due to low cardiac output and poor tissue perfusion, in a septic patient due to problems with oxygen delivery and extraction at the tissue level due to cytokine release and in a patient with acute abdomen and viscus perforation secondary to ischemia.

Chest radiography

The radiographic findings on chest radiography are different in cardiogenic and noncardiogenic pulmonary edema.

Following are radiographic signs suggestive of cardiogenic pulmonary edema: enlargement of pulmonary vasculature (proeminent hillum) with redistribution of the pulmonary blood flow to the upper lobes, proeminent septal lines ( Kerley B lines), acinar areas of increased opacity that coalesce into frank consolidation and relative sparing of the periphery of the lungs. Also the heart size may be enlarged in patients with longstanding history of heart disease but it can be normal in size with an acute valvular dysfunction leading to pulmonary edema. Cardiogenic pulmonary edema is often associated with pleural effusions on the chest radiography. Conversely, the noncardiogenic pulmonary edema is being characterized by patchy diffuse alveolar infiltrates with air bronchograms, involvement of the lung periphery, relative sparing of the upper lobes and lack of vascular engorgement and pulmonary blood flow redistribution.


Bedside transthoracic echocardiography should be the next diagnostic tool to assess the left ventricular and the valvular function in a critically ill patient with signs of pulmonary edema in whom the history, physical examination, laboratory testing and the CXR did not establish the cause of pulmonary edema. The echocardiography is sensitive in identifying  left ventricular systolic dysfunction and valvular abnormalities but may lack sensitivity to for the left ventricular diastolic dysfunction.

Invasive tools to assess the etiology of pulmonary edema

Pulmonary artery catheterization is the gold standard to determine the cause of the pulmonary edema. An elevated pulmonary capillary pressure above 18 mm Hg is diagnostic of cardiogenic pulmonary edema or edema due to volume overload.  Pulmonary artery catheterization can calculate cardiac output and systemic vascular resistance and monitor the response to therapy. Cardiac output is usually low in cardiogenic pulmonary edema due to left ventricular pump failure. Systemic vascular resistance is high as the cardiogenic shock is associated with severe peripheral vasoconstriction as an adaptive body mechanism to protect the perfusion of vital organs in the setting of decrease cardiac output. Complications of pulmonary artery catheterization are hematoma at the puncture site, bleeding, arrhythmia and infections. In a small study done in critically ill patients with hypotension and unclear etiology of pulmonary edema data obtained from a pulmonary artery catheter and two dimensions echocardiography correlated well in 86% of cases.

In summary, the approach of a patient with acute dyspnea and suspected pulmonary edema should be done in a stepwise fashion: first history, physical examination and routine laboratory testing including EKG, cardiac enzymes, BNP. Next step is chest radiography. If diagnostic is still uncertain, bedside echo should be done. If etiology still unclear, the invasive approach with pulmonary artery catheterization would be the final diagnostic tool.

Management of pulmonary edema

The management of pulmonary edema depends largely on the etiology. The mainstay of therapy in cardiogenic pulmonary edema or fluid overload edema is diuretic therapy. Venodilators (nitroglycerin, morphine) play an important role in an effort to decrease the pulmonary capillary pressure and relieve the vascular congestion. Morphine will also cause central inhibition of the respiratory center with improvement of the respiratory rate and some symptomatic relief. Venodilators should be used with caution as they can further drop the blood pressure and the cardiac output in a patient already hypotensive. Often time patients with pulmonary edema will need temporary ventilatory support via mechanical intubation.

The treatment of non cardiogenic pulmonary edema should address the underlying cause, ie antibiotics if the cause of pulmonary edema is sepsis. Until the cause of pulmonary edema is being treated, if the patient requires mechanical ventilation, a lung protective strategy of ventilation should be used with low tidal volume to avoid barotrauma.


Marwick, T. H. (2005). “Dyspnea and risk in suspected coronary disease.” N Engl J Med 353(18): 1963-5.


Roland H. Ingram Jr, E. B. “Dyspnea and Pulmonary Edema.”  Harrison’s principles of Internal Medicine, 16th edition.


Ware, L. B. and M. A. Matthay (2005). “Clinical practice. Acute pulmonary edema.” N Engl J Med353(26): 2788-96.