Heart failure (HF) is the pathophysiologic state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the me tabolizing tissues and/or allows it to do so only from an abnormally elevated diastolic volume. HF is frequently, but not always, caused by a defect in myocardial contraction, and then the term myocardial failure is appropriate. The latter may result from a primary abnormality in heart muscle, as occurs in the cardiomyopathies, in viral myocarditis (Chap. 238), and with excessive programmed cell death (apoptosis). HF also results commonly from coronary atherosclerosis, which interferes with cardiac contraction by causing myocardial infarction and ischemia. HF may also occur in valvular and/or congenital heart disease in which the heart muscle is damaged by the long-standing excessive hemodynamic burden imposed by the valvular abnormality or cardiac malformation.

In other patients with HF, however, a similar clinical syndrome is present but without any detectable abnormality of myocardial function. In some of these patients the normal heart is suddenly presented with a mechanical load that exceeds its capacity, such as an acute hypertensive crisis, rupture of an aortic valve cusp, or massive pulmonary embolism. HF in the presence of normal myocardial function also occurs in chronic conditions in which there is impaired filling of the ventricles due to a mechanical abnormality such as tricuspid and/or mitral stenosis, constrictive pericarditis without myocardial involvement, endocardial fibrosis, and some forms of hypertrophic cardiomyopathy. In many patients with HF, particularly those with valvular or congenital heart disease, there is a combination of impaired myocardial function and hemodynamic overload.

Heart failure should be distinguished from (1) conditions in which there is circulatory congestion secondary to abnormal salt and water retention but in which there is no disturbance of cardiac function per se, as occurs in renal failure; and (2) noncardiac causes of inadequate cardiac output, such as hypovolemic shock (Chap. 38).

The ventricles respond to a chronically increased hemodynamic burden with the development of hypertrophy (Fig. 232-1). When the ventricle is called on to deliver an elevated cardiac output for prolonged periods, as in valvular regurgitation, it develops eccentric hypertrophy, i.e., cavity dilatation, with an increase in muscle mass so that the ratio between wall thickness and ventricular cavity size remains relatively constant early in the process. With chronic pressure overload, as in valvular aortic stenosis or untreated hypertension, concentric ventricular hypertrophy develops; in this condition the ratio between wall thickness and ventricular cavity size increases. In both eccentric and concentric hypertrophy, a stable hyperfunctioning state may exist for many years, but myocardial function may ultimately deteriorate, leading to HF. Often at this time, the ventricle dilates and the ratio between wall thickness and cavity size declines, leading to increased stress on each unit of myocardium, further dilatation, and a vicious circle.

Figure 232-1

Figure 232-1: Patterns of ventricular hypertrophy. Specific patterns of ventricular remodeling occur in response to the imposed augmentation in work load. A pattern of hypertrophic growth characterized as concentric, in which increased mass is out of proportion to chamber volume, is particularly effective in reducing systolic wall stress (0x0003c3) under conditions of heightened pressure load. In contrast, in volume overload conditions, in which the major stimulus is diastolic loading, a predominant finding is a great increase in the cavity size or volume. Although there can be extensive increases in mass, the relationship between mass and volume is either preserved or, in severe cases, reduced. The fundamental response is generated by cellular hypertrophy. However, the configuration of the new contractile tissue is specific and offsets the mechanical stimulus.

Heart failure represents a major public health problem in industrialized nations. It appears to be the only common cardiovascular condition that is increasing in prevalence and incidence. In the United States, HF is responsible for almost 1 million hospital admissions and 40,000 deaths annually. Since HF is more common in the elderly, its prevalence is likely to continue to increase as the population ages.

Causes of Heart Failure

In evaluating patients with HF, it is important to identify not only the underlying but also the precipitating cause. The cardiac abnormality produced by a congenital or acquired lesion such as valvular aortic stenosis may exist for many years and cause no clinical disability. Frequently, however, clinical manifestations of HF are precipitated for the first time in the course of some acute disturbance that places an additional load on a myocardium that is chronically excessively burdened (see below). Such a heart may be compensated but have little additional reserve, and the additional load imposed by a precipitating cause results in further deterioration of cardiac function. Identification of such precipitating causes is of critical importance because their prompt alleviation may be lifesaving. In the absence of underlying heart disease, these acute disturbances do not by themselves lead to HF.

Precipitating Causes

Infection. Patients with pulmonary vascular congestion due to left ventricular failure are more susceptible to pulmonary infection than are normal persons; any infection may precipitate HF. The resulting fever, tachycardia, and hypoxemia and the increased metabolic demands may place a further burden on an overloaded, but compensated, myocardium of a patient with chronic heart disease.

Anemia. In the presence of anemia, the oxygen needs of the metabolizing tissues can be met only by an increase in the cardiac output Although such an increase in cardiac output can be sustained by a normal heart, a diseased, overloaded, but otherwise compensated heart may be unable to augment sufficiently the volume of blood that it delivers to the periphery. In this manner, the combination of anemia and previously compensated heart disease can precipitate HF and lead to inadequate delivery of oxygen to the periphery.

Thyrotoxicosis and pregnancy. Similar to anemia and fever, thyrotoxicosis and pregnancy are also high cardiac output states. The development or intensification of HF in a patient with previously compensated heart disease may actually be one of the first clinical manifestations of hyperthyroidism. Similarly, HF not infrequently occurs for the first time during pregnancy in women with rheumatic valvular disease, in whom cardiac compensation may return following delivery .

Arrhythmias. In patients with compensated heart disease, arrhythmias are among the most frequent precipitating causes of HF. They exert a deleterious effect for a variety of reasons: (a) Tachyarrhythmias reduce the time period available for ventricular filling and in patients with ischemic heart disease they may also cause ischemic myocardial dysfunction. (b) The dissociation between atrial and ventricular contractions characteristic of many brady- and tachyarrhythmias results in the loss of the atrial booster pump mechanism, thereby raising atrial pressures. (c) Cardiac performance may become further impaired because of the loss of normally synchronized ventricular contraction in any arrhythmia associated with abnormal intraventricular conduction. (d) Marked bradycardia associated with complete atrioventricular block or other severe bradyarrhythmias reduces cardiac output unless stroke volume rises reciprocally; this compensatory response cannot occur with serious myocardial dysfunction, even in the absence of HF).

Rheumatic, viral, and other forms of myocarditis. Acute rheumatic fever and a variety of other inflammatory or infectious processes affecting the myocardium may precipitate HF in patients with or without preexisting heart disease

Infective endocarditis. The additional valvular damage, anemia, fever, and myocarditis that often occur as a consequence of infective endocarditis may, singly or in concert, frequently precipitate HF

Physical, dietary, fluid, environmental, and emotional excesses. The sudden augmentation of sodium intake as with a large meal, the inappropriate discontinuation of pharmaceuticals to treat HF, blood transfusions, physical overexertion, excessive environmental heat or humidity, and emotional crises all may precipitate HF in patients with heart disease who were previously compensated.

Systemic hypertension. Rapid elevation of arterial pressure, as may occur in some instances of hypertension of renal origin or upon discontinuation of antihypertensive medication in patients with essential hypertension, may result in cardiac decompensation

Myocardial infarction. In patients with chronic but compensated ischemic heart disease, a fresh infarct, sometimes otherwise silent clinically, may further impair ventricular function and precipitate HF

Pulmonary embolism. Physically inactive patients with low cardiac output are at increased risk of developing thrombi in the veins of the lower extremities or the pelvis. Pulmonary emboli may result in further elevation of pulmonary arterial pressure, which in turn may produce or intensify ventricular failure. In the presence of pulmonary vascular congestion, such emboli also may cause pulmonary infarction.

A systematic search for these precipitating causes should be made in every patient with the new development or recent intensification of HF. If properly recognized, the precipitating cause of HF usually can be treated more effectively than the underlying cause. Therefore, the prognosis in patients with HF in whom a precipitating cause can be identified, treated, and eliminated is more favorable than in patients in whom the underlying disease process has progressed to the point of producing HF without a precipitating cause.

Forms of Heart Failure

HF may be described as systolic or diastolic, high-output or low-output, acute or chronic, right-sided or left-sided, and forward or backward. These descriptors are often useful in a clinical setting, particularly early in the patient's course, but late in the course of chronic HF the differences between them often become blurred.

Systolic Versus Diastolic Failure

The distinction between these two forms of HF, described in Fig. 231-9, relates to whether the principal abnormality is the inability of the ventricle to contract normally and expel sufficient blood (systolic failure) or to relax and/or fill normally (diastolic failure). The major clinical manifestations of systolic failure relate to an inadequate cardiac output with weakness, fatigue, reduced exercise tolerance, and other symptoms of hypoperfusion, while in diastolic HF the manifestations relate principally to the elevation of filling pressures. Many patients, particularly those who have both ventricular hypertrophy and dilatation, exhibit abnormalities both of contraction and relaxation coexist.

Diastolic HF may be caused by increased resistance to ventricular inflow and reduced ventricular diastolic capacity (constrictive pericarditis and restrictive, hypertensive, and hypertrophic cardiomyopathy), impaired ventricular relaxation (acute myocardial ischemia), and myocardial fibrosis and infiltration (restrictive cardiomyopathy).

High-Output versus Low-Output Heart Failure

It is useful to classify patients with HF into those with a low cardiac output, i.e., low-output HF, and those with an elevated cardiac output, i.e., high-output HF. The former occurs secondary to ischemic heart disease, hypertension, dilated cardiomyopathy, and valvular and pericardial disease, while the latter is seen in patients with HF and hyperthyroidism, anemia, pregnancy, arteriovenous fistulas, beriberi, and Paget's disease. In clinical practice, however, low-output and high-output HF cannot always be readily distinguished. The normal range of cardiac output is wide [2.2 to 3.5 (L/min)/m2]; in many patients with so-called low-output HF, the cardiac output may actually be just within the normal range at rest (although lower than it had been previously), but it fails to rise normally during exertion. On the other hand, in patients with so-called high-output HF, the output may not exceed the upper limits of normal (although it would have been elevated had it been measured before HF supervened); rather, it may have fallen to within normal limits. Regardless of the absolute level of the cardiac output, however, cardiac failure may be said to be present when the characteristic clinical manifestations described below are accompanied by a depression of the curve relating ventricular end-diastolic volume to cardiac performance (see Fig. 231-6).

An integral physiologic component of systolic HF is the delivery of an inadequate quantity of oxygen required by the metabolizing tissues. In the absence of peripheral shunting of blood, this is reflected in an abnormal widening of the normal arterial-mixed venous oxygen difference (35 to 50 mL/L in the basal state). In mild cases, such an abnormality may not be present at rest but becomes evident only during exertion or other hypermetabolic states. In patients with high cardiac output states, such as those associated with arteriovenous fistula or thyrotoxicosis, the arterial-mixed venous oxygen difference is normal or low. The mixed venous oxygen saturation is raised by the admixture of blood that has been diverted away from the metabolizing tissues, and it may be presumed that even in these patients the delivery of oxygen to the latter is reduced despite the normal or even elevated mixed venous oxygen saturation. When HF occurs in such patients, the arterial-mixed venous oxygen difference, regardless of the absolute value, still exceeds the level that existed prior to the development of HF. Therefore, the cardiac output, though normal or even elevated, is lower than before HF supervened.

In most forms of high-output HF, the heart is called on to pump abnormally large quantities of blood in order to deliver the oxygen required by the metabolizing tissues. The hemodynamic burden placed on the myocardium by the increased flow load resembles that produced by chronic aortic regurgitation. In addition, thyrotoxicosis and beriberi may also impair myocardial metabolism directly, while very severe anemia may interfere with myocardial function by producing myocardial anoxia, especially in the subendocardium and in the presence of underlying obstructive coronary artery disease.

Acute versus Chronic Heart Failure

The prototype of acute HF is the sudden development of a large myocardial infarction or rupture of a cardiac valve in a patient who previously was entirely well. Chronic HF is typically observed in patients with dilated cardiomyopathy or multivalvular heart disease that develops or progresses slowly. Acute HF is usually predominantly systolic, and the sudden reduction in cardiac output often results in systemic hypotension without peripheral edema. In contrast, in chronic HF, arterial pressure is ordinarily well maintained until very late in the course, but there is often accumulation of edema.

Right-Sided versus Left-Sided Heart Failure

Many of the clinical manifestations of HF result from the accumulation of excess fluid behind either one or both ventricles (Chaps. 32 and 37). This fluid usually localizes upstream to (behind) the ventricle that is initially affected. For example, patients in whom the left ventricle is hemodynamically overloaded (e.g., aortic stenosis) or weakened (e.g., postmyocardial infarction) develop dyspnea and orthopnea as a result of pulmonary congestion, a condition referred to as left-sided HF. In contrast, when the underlying abnormality affects the right ventricle primarily (e.g., congenital valvular pulmonic stenosis or pulmonary hypertension secondary to pulmonary thromboembolism), symptoms resulting from pulmonary congestion are uncommon, and edema, congestive hepatomegaly, and systemic venous distention, i.e., clinical manifestations of right-sided HF, are more prominent. When HF has existed for months or years, such localization of excess fluid behind the failing ventricle may no longer exist. For example, patients with long-standing aortic valve disease or systemic hypertension may develop ankle edema, congestive hepatomegaly, and systemic venous distention late in the course of their disease, even though the abnormal hemodynamic burden initially was placed on the left ventricle. This occurs in part because of the secondary pulmonary hypertension and resultant right-sided HF but also because of the retention of salt and water characteristic of HF (Chap. 37). The muscle bundles composing both ventricles are continuous, and both ventricles share a common wall, the interventricular septum. Also, biochemical changes that occur in HF and that may be involved in the impairment of myocardial function (Chap. 231), such as norepinephrine depletion and alterations in the activity of myosin ATPase, occur in the myocardium of both ventricles, regardless of the specific chamber on which the abnormal hemodynamic burden is placed initially.

Backward versus Forward Heart Failure

For many years a controversy has revolved around the question of the mechanism of the clinical manifestations resulting from HF. The concept of backward HF contends that in HF, one or the other ventricle fails to discharge its contents or fails to fill normally. As a consequence, the pressures in the atrium and venous system behind the failing ventricle rise, and retention of sodium and water occurs as a consequence of the elevation of systemic venous and capillary pressures and the resultant transudation of fluid into the interstitial space (Chap. 37). In contrast, the proponents of the forward HF hypothesis maintain that the clinical manifestations of HF result directly from an inadequate discharge of blood into the arterial system. According to this concept, salt and water retention is a consequence of diminished renal perfusion and excessive proximal tubular sodium reabsorption and of excessive distal tubular reabsorption through activation of the renin-angiotensin-aldosterone (RAA) system.

A rigid distinction between backward and forward HF (like a rigid distinction between right and left HF) is artificial, since both mechanisms appear to operate to varying extents in most patients with HF. However, the rate of onset of HF often influences the clinical manifestations. For example, when a large portion of the left ventricle is suddenly destroyed, as in myocardial infarction, although stroke volume and blood pressure are suddenly reduced (both manifestations of forward failure), the patient may succumb to acute pulmonary edema, a manifestation of backward failure. If the patient survives the acute insult, clinical manifestations resulting from a chronically depressed cardiac output, including the abnormal retention of fluid within the systemic vascular bed, may develop. Similarly, in the case of massive pulmonary embolism, the right ventricle may dilate and the systemic venous pressure may rise to high levels (backward failure), or the patient may develop shock secondary to low cardiac output (forward failure), but this low-output state may have to be maintained for some days before sodium and water retention sufficient to produce peripheral edema occurs.

Redistribution of Cardiac Output

In HF, systemic blood flow is redistributed so that the delivery of oxygen to vital organs, such as the brain and myocardium, is maintained at normal or near-normal levels, while flow to less critical areas, such as the cutaneous and muscular beds and the viscera, is reduced. This redistribution serves as an important compensatory mechanism when cardiac output is reduced. It is most marked when a patient with HF exercises, but as HF advances, redistribution occurs even in the basal state. Vasoconstriction mediated by the adrenergic nervous system is largely responsible for redistribution, which in turn may be responsible for many of the clinical manifestations of HF, such as fluid accumulation (reduction of renal blood flow), low-grade fever (reduction of cutaneous flow), and fatigue (reduction of muscle flow).

Salt and Water Retention

When the volume of blood pumped by the left ventricle into the systemic vascular bed is reduced, a complex sequence of adjustments occurs that ultimately results in the abnormal accumulation of fluid. On the one hand, many of the troubling clinical manifestations of HF are secondary to this excessive retention of fluid; on the other, this abnormal fluid accumulation and the expansion of blood volume that accompanies it also constitute an important compensatory mechanism that tends to maintain cardiac output and therefore perfusion of the vital organs. Except in the terminal stages of HF, the ventricle operates on an ascending, albeit depressed and flattened, function curve (Fig. 231-6, p. 1313), and the augmented ventricular end-diastolic volume and pressure characteristic of HF must be regarded as helping to maintain the reduced cardiac output, despite causing pulmonary and/or systemic venous congestion.

Congestive HF is also characterized by a complex series of neurohumoral adjustments. The activation of the adrenergic nervous system is discussed on p. 1315; there is also activation of the RAA system and increased release of antidiuretic hormone and endothelin. These influences elevate systemic vascular resistance and enhance sodium and water retention and potassium excretion. These actions are, to a minor extent, opposed by the release of atrial and brain natriuretic peptide, which also occurs in congestive HF. Patients with severe HF may exhibit a reduced capacity to excrete a water load, which may result in dilutional hyponatremia. In the presence of HF, effective filling of the systemic arterial bed is reduced, a condition that initiates the renal and hormonal changes mentioned above (Fig. 37-2).

The elevation of systemic venous pressure and the alterations of renal and adrenal function characteristic of HF vary in their relative importance in the production of edema in different patients. The RAA axis is activated most intensely by acute HF, and its activity tends to decline as HF becomes chronic. In patients with tricuspid valve disease or constrictive pericarditis, the elevated venous pressure and the transudation of fluid from systemic capillaries appear to play the dominant role in edema formation. On the other hand, severe edema may be present in patients with ischemic or hypertensive heart disease, in whom systemic venous pressure is within normal limits or is only minimally elevated. In such patients, the retention of salt and water is probably due primarily to a redistribution of cardiac output and a concomitant reduction in renal perfusion, as well as activation of the RAA axis. Regardless of the mechanisms involved in fluid retention, untreated patients with chronic congestive HF have elevations of total blood volume, interstitial fluid volume, and body sodium. These abnormalities diminish after clinical compensation has been achieved by effective treatment, especially with diuretics.

Clinical Manifestations of Heart Failure


Respiratory distress that occurs as the result of increased effort in breathing is the most common symptom of HF (Chap. 32). In early HF, dyspnea is observed only during activity, when it may simply represent an aggravation of the breathlessness that occurs normally under these circumstances. As HF advances, however, dyspnea appears with progressively less strenuous activity and ultimately is present even when the patient is at rest. The principal difference between exertional dyspnea in normal persons and in patients with HF is the degree of activity necessary to induce this symptom. Cardiac dyspnea is observed most frequently in patients with elevations of pulmonary venous and capillary pressures. Such patients usually have engorged pulmonary vessels and interstitial pulmonary edema, which may be evident on radiologic examination. This interstitial pulmonary edema reduces the compliance of the lungs and thereby increases the work of the respiratory muscles required to inflate the lungs. The activation of receptors in the lungs results in the rapid, shallow breathing characteristic of cardiac dyspnea. The oxygen cost of breathing is increased by the excessive work of the respiratory muscles. This is coupled with the diminished delivery of oxygen to these muscles, which occurs as a consequence of the reduced cardiac output and which may contribute to fatigue of the respiratory muscles and the sensation of shortness of breath.


Dyspnea in the recumbent position is usually a later manifestation of HF than exertional dyspnea. Orthopnea occurs because of the redistribution of fluid from the abdomen and lower extremities into the chest during recumbency causing an increase in the pulmonary capillary hydrostatic pressure, as well as elevation of the diaphragm accompanying supine posture. Patients with orthopnea must elevate their heads on several pillows at night and frequently awaken short of breath or coughing (the so-called nocturnal cough) if their heads slip off the pillows. The sensation of breathlessness is usually relieved by sitting upright, since this position reduces venous return and pulmonary capillary pressure, and many patients report that they find relief from sitting in front of an open window. In advanced HF, orthopnea may become so severe that patients cannot lie down at all and must spend the entire night in a sitting position. On the other hand, in other patients with long-standing, severe left ventricular failure, symptoms of pulmonary congestion may actually diminish with time as the function of the right ventricle becomes impaired.

Paroxysmal (Nocturnal) Dyspnea

This term refers to attacks of severe shortness of breath and coughing that generally occur at night, usually awaken the patient from sleep, and may be quite frightening. Though simple orthopnea may be relieved by sitting upright at the side of the bed with legs dependent, in the patient with paroxysmal nocturnal dyspnea, coughing and wheezing often persist even in this position. Paroxysmal nocturnal dyspnea may be caused in part by the depression of the respiratory center during sleep, which may reduce ventilation sufficiently to lower arterial oxygen tension, particularly in patients with interstitial lung edema and reduced pulmonary compliance. Also, ventricular function may be further impaired at night because of reduced adrenergic stimulation of myocardial function. Cardiac asthma is closely related to paroxysmal nocturnal dyspnea and nocturnal cough and is characterized by wheezing secondary to bronchospasm-most prominent at night. Acute pulmonary edema (Chap. 32) is a severe form of cardiac asthma due to marked elevation of pulmonary capillary pressure leading to alveolar edema, associated with extreme shortness of breath, rales over the lung fields, and the transudation and expectoration of blood-tinged fluid. If not treated promptly, acute pulmonary edema may be fatal.

Cheyne-Stokes Respiration

Also known as periodic respiration or cyclic respiration, Cheyne-Stokes respiration is characterized by diminished sensitivity of the respiratory center to arterial PCO2. There is an apneic phase, during which the arterial PO2 falls and the arterial PCO2 rises. These changes in the arterial blood stimulate the depressed respiratory center, resulting in hyperventilation and hypocapnia, followed in turn by recurrence of apnea. Cheyne-Stokes respiration occurs most often in patients with cerebral atherosclerosis and other cerebral lesions, but the prolongation of the circulation time from the lung to the brain that occurs in HF, particularly in patients with hypertension and coronary artery disease and associated cerebral vascular disease, also appears to precipitate this form of breathing.

Fatigue and Weakness

These nonspecific but common symptoms of HF are related to the reduction of perfusion of skeletal muscle. Exercise capacity is reduced by the limited ability of the failing heart to increase its output and deliver oxygen to the exercising muscle.

Abdominal Symptoms

Anorexia and nausea associated with abdominal pain and fullness are frequent complaints and may be related to the congested liver and portal venous system.

Cerebral Symptoms

In severe HF, particularly in elderly patients with accompanying cerebral arteriosclerosis, reduced cerebral perfusion, and arterial hypoxemia, there may be alterations in the mental state characterized by confusion, difficulty in concentration, impairment of memory, headache, insomnia, and anxiety. Nocturia is common in HF and may contribute to insomnia.

Physical Findings

In moderate HF, the patient is in no distress at rest except that he or she may be uncomfortable when lying flat for more than a few minutes. In more severe HF, the pulse pressure may be diminished, reflecting a reduction in stroke volume, and the diastolic arterial pressure may be elevated as a consequence of generalized vasoconstriction. In acute HF, severe hypotension may be present. There may be cyanosis of the lips and nail beds (Chap. 36) and sinus tachycardia, and the patient may insist on sitting upright. Systemic venous pressure is often abnormally elevated in HF, and this may be reflected in distention of the jugular veins. In the early stages of HF, the venous pressure may be normal at rest but may become abnormally elevated during and immediately after exertion as well as with sustained pressure on the abdomen (positive abdominojugular reflux).

Third and fourth heart sounds are often audible but are not specific for HF, and pulsus alternans, i.e., a regular rhythm in which there is alternation of strong and weak cardiac contractions and therefore alternation in the strength of the peripheral pulses, may be present. Pulsus alternans, a sign of severe HF, may be detected by sphygmomanometry and in more severe instances by palpation; it frequently follows an extrasystole and is observed most commonly in patients with cardiomyopathy or hypertensive or ischemic heart disease.

Pulmonary Rales

Moist, inspiratory, crepitant rales and dullness to percussion over the lung bases are common in patients with HF and elevated pulmonary venous and capillary pressures. In patients with pulmonary edema, rales may be heard widely over both lung fields; they are frequently coarse and sibilant and may be accompanied by expiratory wheezing. Rales may, however, be caused by many conditions other than left ventricular failure. Some patients with long-standing HF have no rales because of increased lymphatic drainage of alveolar fluid.

Cardiac Edema

This is usually symmetric and dependent, occurring in the legs, particularly in the pretibial region and ankles in ambulatory patients, in whom it is most prominent in the evening. Cardiac edema occurs in the sacral region of patients who are bed-ridden. Pitting edema of the arms and face occurs rarely and then only late in the course of HF.

Hydrothorax and Ascites

Pleural effusion in congestive HF results from the elevation of pleural capillary pressure and transudation of fluid into the pleural cavities. Since the pleural veins drain into both the systemic and pulmonary veins, hydrothorax occurs most commonly with marked elevation of pressure in both venous systems but also may be seen with marked elevation of pressure in either venous bed. It is more frequent in the right pleural cavity than in the left. Ascites also occurs as a consequence of transudation and results from increased pressure in the hepatic veins and the veins draining the peritoneum (Chap. 46). Marked ascites occurs most frequently in patients with tricuspid valve disease and constrictive pericarditis.

Congestive Hepatomegaly

An enlarged, tender, pulsating liver also accompanies systemic venous hypertension and is observed not only in the same conditions in which ascites occurs but also in milder forms of HF from any cause. With prolonged, severe hepatomegaly, as in patients with tricuspid valve disease or chronic constrictive pericarditis, enlargement of the spleen, i.e., congestive splenomegaly, may also occur.


This is a late finding in HF and is associated with elevations of both the direct- and indirect-reacting bilirubin; it results from impairment of hepatic function secondary to hepatic congestion and the hepatocellular hypoxia associated with central lobular atrophy. Hepatic enzymes are frequently elevated. If hepatic congestion occurs acutely, the jaundice may be severe and the enzymes strikingly elevated.

Cardiac Cachexia

With severe chronic HF there may be serious weight loss and cachexia because of (1) elevation of circulating concentrations of tumor necrosis factor; (2) elevation of the metabolic rate, which results in part from the extra work performed by the respiratory muscles, the increased oxygen needs of the hypertrophied heart, and/or the discomfort associated with severe HF; (3) anorexia, nausea, and vomiting due to central causes, to digitalis intoxication, or to congestive hepatomegaly and abdominal fullness; (4) impairment of intestinal absorption due to congestion of the intestinal veins; and (5) rarely, due to protein-losing enteropathy in patients with particularly severe failure of the right side of the heart.

Other Manifestations

With reduction of blood flow, the extremities may be cold, pale, and diaphoretic. Urine flow is depressed, and the urine contains albumin and has a high specific gravity and a low concentration of sodium. In addition, prerenal azotemia may be present. In patients with long-standing severe HF, impotence and depression are common.

Roentgenographic and Echocardiographic Findings

In addition to the enlargement of the particular chambers characteristic of the lesion responsible for HF, distention of pulmonary veins and redistribution to the apices is common in patients with HF and elevated pulmonary vascular pressures. Also, pleural effusions may be evident and associated with interlobar effusions.

Differential Diagnosis

The diagnosis of congestive HF may be established by observing some combination of the clinical manifestations of HF described above, together with the findings characteristic of one of the etiologic forms of heart disease. Table 232-1 shows the Framingham criteria, which are useful in the diagnosis of HF. Since chronic HF is often associated with cardiac enlargement, the diagnosis should be questioned, but is by no means excluded, when all chambers are normal in size. Two-dimensional echocardiography (Chap. 227) is particularly useful in assessing the dimensions of each cardiac chamber. HF is sometimes difficult to distinguish from pulmonary disease, and the differential diagnosis is discussed in Chap. 32. Pulmonary embolism also presents many of the manifestations of HF, but hemoptysis, pleuritic chest pain, a right ventricular lift, and the characteristic mismatch between ventilation and perfusion on lung scan should point to this diagnosis.


Figure 232-3

Figure 232-3: Chest roentgenogram of patient with heart failure. This roentgenogram demonstrates cardiomegaly (cardiothoracic ratio 0.77), pulmonary congestion, and bilateral pleural effusions (note blunted costophrenic angles). [JB Young: Assessment of heart failure, in WS Colucci: Heart failure: Cardiac Function and Dysfunction, in E Braunwald (series ed): Atlas of Heart Diseases, vol 4. Philadelphia, Current Medicine, 1995, p 7.16.]

Table 232-1: Framingham Criteria for Diagnosis of Congestive Heart Failurea


Paroxysmal nocturnal dyspnea

Neck vein distention



Acute pulmonary edema

S3 gallop

Increased venous pressure (>16 cmH2O)

Positive hepatojugular reflux


Extremity edema

Night cough

Dyspnea on exertion


Pleural effusion

Vital capacity reduced by one-third from normal

Tachycardia (0x002265120 bpm)


Weight loss 0x0022654.5 kg over 5 days' treatment

aTo establish a clinical diagnosis of congestive heart failure by these criteria, at least one major and two minor criteria are required.

Ankle edema may be due to varicose veins, cyclic edema, or gravitational effects (Chap. 37), but in these patients there is no jugular venous hypertension at rest or with pressure over the abdomen. Edema secondary to renal disease can usually be recognized by appropriate renal function tests and urinalysis and is rarely associated with elevation of venous pressure. Enlargement of the liver and ascites occur in patients with hepatic cirrhosis and also may be distinguished from HF by normal jugular venous pressure and absence of a positive abdominojugular reflux.


(See Practice Guidelines, Table 232-4) The treatment of HF may be divided into four components: (1) removal of the precipitating cause, (2) correction of the underlying cause, (3) prevention of deterioration of cardiac function, and (4) control of the congestive HF state. The first two components are discussed in other chapters together with each specific disease entity or complication. Examples of removal of precipitating causes are the treatment of pneumococcal pneumonia or the restoration of sinus rhythm in a patient with atrial fibrillation. In many instances, surgical treatment will correct or at least alleviate the underlying cause of HF. The third component of the treatment of HF, i.e., the prevention of deterioration of cardiac function, involves the administration of angiotensin-converting enzyme (ACE) inhibitors and 0x0003b2-adrenergic blockers as well as reduction of cardiac work load. Control of the congestive heart failure state requires reduction of the excessive retention of salt and water as well as enhancement of myocardial contractility. The vigor with which each of these measures is pursued in any individual patient should depend on the severity of HF and the tempo of the disease. Following effective treatment, recurrence of the clinical manifestations of HF can often be prevented by continuing those measures that were originally effective.

Table 232-4: Practice Guidelines for Heart Failure

  1. Evaluation
    1. Assess functional status by NY Heart Association classification
    2. Assess fluid status to determine need for diuretics
    3. Assess left ventricular (LV) ejection fraction to distinguish between systolic, diastolic, or combined HF (echocardiography or radionuclide angiography)
    4. Assess invasive hemodynamics in patients unresponsive to treatment and/or transplant candidates
  2. Prevention
    1. Control coronary risk factors (Chap. 241)
    2. Institute reperfusion strategies in acute myocardial infarction (Chap. 242)
    3. Prescribe ACE inhibition and/or beta blockade in patients with LV dysfunction without HF
  3. General therapeutic measures
    1. Restrict salt intake to <3 g qd
    2. Recommend regular, moderate exercise
    3. Avoid antiarrhythmic agents for asymptomatic arrhythmias
    4. Avoid nonsteroidal anti-inflammatory agents
    5. Provide influenzal and pneumococcal immunization
  4. Diuretics
    1. Administer diuretics for all pts with HF with fluid accumulation to achieve normal jugular venous pressure and relief of edema
    2. Weigh daily to select/adjust dose
    3. Treat diuretic resistance
      1. IV administration
      2. Use 0x0022652 diuretics in combination (e.g. furosemide and metolazone)
    4. Administer short-term dopamine to enhance renal blood flow
  5. ACE inhibitors
    1. Administer to all patients with LV systolic failure and LV dysfunction without heart failure
    2. Contraindications:
      1. High-output angioedema or anuric renal failure
      2. Pregnancy
      3. Hypotension
      4. Creatinine > 265 0x0003bcmol/L (3 mg/dL)
      5. Serum K > 5.5 mmol/L
      6. Bilateral renal artery stenosis.
  6. 0x0003b2-Adrenergic blockers
    1. Administer to all NYHA class II or III pts with systolic HF, often together with ACE inhibitors and diuretics
    2. Contraindications
      1. Bronchospastic disease
      2. Symptomatic bradycardia or advanced heart block
      3. Instability
  7. Digitalis
    1. Use in pts with LV systolic HF along with diuretics, ACE inhibitors, beta blocker; especially useful in pts with atrial fibrillation
  8. Other measures
    1. Consider hydralazine-iosorbide combination in patients intolerant of ACE inhibition
    2. Use angiotensin-receptor blocker in pts who develop angioedema or cough with ACE inhibitor
    3. Consider spironolactone in patients with class IV symptoms
    4. Do not use calcium antagonists for treatment of heart failure and avoid them for treatment of angina or hypertension in pts with heart failure
  9. Antiarrhythmic therapy
    1. Antiarrhythmic drugs (Chap. 230) are not recommended for pts with asymptomatic or nonsustained ventricular arrhythmias
    2. Class I antiarrhythmics should be avoided except in acute life-threatening arrhythmias
    3. Class III antiarrhythmics, especially amiodarone, may be used to treat atrial arrhythmias but not for the prevention of sudden death.

While a simple rule for the treatment of all patients with HF cannot be formulated because of its varied etiologies, hemodynamic features, clinical manifestations, and severity of HF, insofar as the treatment of chronic congestive failure is concerned, the administration of an ACE inhibitor retards the development of HF and should be begun early in patients with left ventricular systolic dysfunction (ejection fraction < 0.40), even if they are asymptomatic. Then, as symptoms develop, simple measures such as moderate restriction of activity and sodium intake and oral diuretics should be tried. 0x0003b2-adrenergic receptor blockers and digitalis glycosides are given for patients with systolic HF. If these measures are insufficient, the next step is more rigorous restriction of salt intake and higher doses and multiple diuretics. If HF persists, hospitalization with rigid salt restriction, bed rest, intravenous vasodilators, and positive inotropic agents are tried. Assisted circulation and cardiac transplantation (Chap. 233) are considered for patients with severe, intractable HF and a poor prognosis.

Prevention of Deterioration of Myocardial Infarction

Chronic activation of the RAA axis and of the sympathetic nervous systems in HF result in a maladaptive response and cause further deterioration of cardiac function and/or potentially fatal arrhythmias (Chap. 231). Drugs that block these two systems have been found to be useful in the management of HF (Tables 232-2 and 232-3).

Table 232-2: Overview of Angiotensin-Converting Enzyme Inhibitors in Heart Failure


Odds Ratio

95% Confidence Interval

Total mortality



Mortality or hospitalization



Progressive heart failure



Sudden death



Fatal myocardial infarction



Total mortality



0x002003Class 1



0x002003Class 2



0x002003Class 3



0x002003Class 4



EF >0.25



EF 0x0022640.25



NOTE: EF, ejection fraction

Table 232-3: Clinical Trials in Heart Failure


Beta Blockade

Aldosterone Antagonist

Trial name





Bisoprolol (B1 selective)

Metoprolol (B1 selective)


Age (avg, years)








Male %




























Annual mortality, %




Mortality reduction




0x002003All cause




0x002003Sudden death




0x002003Pump failure death




Hospital admissions for HF




Angiotensin-Converting Enzyme Inhibitors

In many patients with HF, the left ventricular afterload is increased as a consequence of the several neural and humoral influences that act to constrict the peripheral vascular bed. In addition to the vasoconstriction, the ventricular end-diastolic and -systolic volumes rise in systolic HF. As a consequence of the operation of Laplace's law, which relates myocardial wall tension to the product of intraventricular pressure and radius (both of which may become elevated in HF), the aortic impedance, i.e., the force that opposes left ventricular ejection, or the ventricular afterload, rises, which reduces stroke volume (Fig. 231-10, p. 1316). In many patients with systolic HF, a modest reduction of systemic vascular resistance and afterload elevates the stroke volume and reduces the elevated ventricular filling pressure of the failing ventricle.

The pharmacologic reduction of impedance to left ventricular ejection with an ACE inhibitor represents an important component of the management of HF. This approach may be particularly helpful in (but is by no means limited to) patients with systolic HF due to myocardial infarction (Chap. 243), and in patients with valvular regurgitation (Chap. 236). ACE inhibition should not be used in hypotensive patients. In patients with both acute and chronic systolic HF who are treated with ACE inhibitors, cardiac output rises, the pulmonary wedge pressure falls, the signs and symptoms of HF are relieved, and a new steady state is achieved in which cardiac output is higher and afterload lower with no or only mild reduction of arterial pressure. The administration of ACE inhibitors has been shown to prevent or retard the development of HF in patients with left ventricular dysfunction without HF, to reduce symptoms, enhance exercise performance, and to reduce long-term mortality when they are begun in such patients shortly after acute myocardial infarction. These beneficial effects are related only in part to the salutary hemodynamic effects, i.e., the reduction of preload and afterload. Their major effect appears to be on inhibition of local (tissue) renin-angiotensin systems.

Lisinopril in doses of 20 mg qd or enalapril 10 mg bid have been shown to be useful in the management of heart failure.

Angiotensin Receptor Blockers

In patients who cannot tolerate ACE inhibitors (because of cough, angioneurotic edema, leukopenia), an angiotensin II receptor blocker (type AT1) antagonist (e.g., losartan 50 mg qid) may be used instead.

Aldosterone Antagonist

The activation of the RAA axis in HF increases not only circulating and tissue angiotensin II but also aldosterone. The latter, in addition to causing sodium retention and worsening edema (Chaps. 331 and 37), causes sympathetic activation, myocardial, vascular, and perivascular fibrosis and reduces arterial compliance. In one large multicenter trial in patients with advanced heart failure and reduced ejection fraction (RALES), spironolactone, 25 mg/d reduced total mortality, as well as sudden death and death from pump failure (Table 232-3). Since spironolactone is also a useful diuretic (see below), its widespread use in systolic heart failure should be considered.

0x0003b2-Adrenoceptor Blockers

While the abrupt administration of large doses of 0x0003b2-adrenergic receptor blockers can intensify HF, the administration of gradually escalating doses of metoprolol, carvedilol, and bisoprolol have been reported to improve the symptoms of HF, and to reduce all-cause death, cardiovascular death, sudden death, and pump failure death (Table 232-3). In patients with moderately severe HF (classes II and III), the administration of 12.5 mg metoprolol CR/XL qd, increasing over 4 weeks to a target dose of 200 mg qid, has been shown to be beneficial. 0x0003b2-Adrenoceptor blockers are not indicated in HF patients who are unstable, in New York Heart Association Class IV, in HF patients shortly after acute myocardial infarction, or in those with HF and normal ejection fraction, i.e., with diastolic HF.

Reduction of Cardiac Work Load

This consists of reducing physical activity, instituting emotional rest, and reducing afterload (see above). Modest restriction of physical activity in mild cases and rest in bed or in a chair in severe failure are useful. In acute, severe failure, meals should be small in quantity, but more frequent, and every effort should be made to diminish the patient's anxiety; sometimes drugs such as diazepam (2 to 5 mg tid) for several days are useful. Physical and emotional rest tends to lower arterial pressure and reduce the load on the myocardium by diminishing the requirements for cardiac output.

Reduced physical exertion should be continued for several days after the patient's condition has stabilized. The hazards of phlebothrombosis and pulmonary embolism which occur with bed rest may be reduced with anticoagulants, leg exercises, and elastic stockings. Absolute bed rest is rarely required or advisable, and the patient should ordinarily be encouraged to sit in a chair. Heavy sedation should be avoided. In ambulatory patients with chronic, moderately severe HF, additional periods of rest on weekends frequently allow continuation of gainful employment. Following recovery from HF, the patient's activities should be assessed, and often, professional, community, and/or family responsibilities should be curtailed. Intermittent rest during the day (e.g., a scheduled 1-h nap or rest following lunch) and the avoidance of strenuous exertion are often helpful. Regular, nonexhausting exercise such as walking or riding a stationary-bicycle ergometer as tolerated should be employed once the patient has become compensated. Weight reduction by restriction of caloric intake in obese patients with HF also diminishes cardiac work load and is an essential component of the therapeutic program.

Control of Excessive Fluid

Many of the clinical manifestations of HF result from expansion of the extracellular fluid volume. A negative sodium balance can be achieved by reducing the dietary intake and increasing the urinary excretion of this ion with the aid of diuretics. Rarely, in severe HF, mechanical removal of extracellular fluid by means of thoracentesis and paracentesis may be necessary.


In patients with mild HF, symptomatic improvement may result simply from reducing the sodium intake, particularly if accompanied by periods of physical rest. The normal diet contains approximately 6 to 10 g sodium chloride; this intake can be reduced by half simply by excluding salt-rich foods and salt added at the table. Reduction of the ordinary dietary intake to approximately one-fourth of normal may be achieved if, in addition, all salt is omitted from cooking. In patients with severe HF who have fluid accumulation despite diuretic therapy (see below), the dietary intake of sodium chloride should be reduced to between 500 and 1000 mg, and in order to achieve this, milk, cheese, bread, cereals, canned vegetables and soups, some salted cuts of meat, and some fresh vegetables (including spinach, celery, and beets) must be eliminated. A variety of fresh fruit, green vegetables, specially processed breads and milk, and salt substitutes are permissible. Late in the course of HF, dilutional hyponatremia may develop in patients who are unable to excrete a water load, sometimes because of excessive secretion of antidiuretic hormone. In such cases, water intake as well as sodium intake must be restricted.

Calories should be restricted in obese patients with HF. In patients with severe HF and cardiac cachexia, on the other hand, an attempt must be made to maintain nutritional intake and to avoid caloric and vitamin deficiencies; nutritional supplements may be in order.


Diuretics should be given to relieve fluid accumulation and thus reduce or prevent edema and jugular venous distention. A variety of diuretic agents are available (Table 246-6, p. 1422), and almost all are effective in patients with mild HF. However, in the more severe forms of HF, the selection of diuretics is more difficult, and abnormalities in serum electrolytes must be taken into account. Overtreatment must be avoided, since the resultant hypovolemia may reduce cardiac output, interfere with renal function, and produce profound weakness and lethargy.

Thiazide Diuretics

These agents are used widely and are useful by themselves in patients with mild HF and in combination with other diuretics in those with severe HF. In patients with chronic mild or moderate HF, the continued administration of a thiazide diuretic abolishes or diminishes the need for rigid dietary sodium restriction, although salty foods and table salt still should be avoided. Thiazide diuretics reduce the reabsorption of sodium and chloride in the first half of the distal convoluted tubule and a portion of the cortical ascending limb of the loop of Henle, and water follows the unreabsorbed salt. Thiazides fail to increase free water clearance and in some instances reduce it. This may result in the excretion of a hypertonic urine and may contribute to dilutional hyponatremia. As a consequence of increased delivery of sodium to the distal nephron, sodium-potassium ion exchange is enhanced, and kaliuresis results. In contrast to the loop diuretics, which enhance calcium excretion, the thiazides have the opposite effect.

Thiazide diuretics are effective and useful in the treatment of HF as long as the glomerular filtration rate exceeds approximately 50% of normal. Chlorothiazide is administered in doses of up to 500 mg every 6 h. Many derivatives of this compound are available but differ principally in dosage and duration of action. Chlorthalidone (25 to 50 mg/d) is especially useful since it may be administered once daily.

Potassium depletion and metabolic alkalosis (the latter due to increased H+ secretion as a substitute for the depleted intracellular stores of potassium) are the chief adverse metabolic effects following prolonged administration of the thiazides, of metolazone, and of the loop diuretics. Hypokalemia may seriously enhance the dangers of digitalis intoxication (see below), and induce fatigue and lethargy; these may be prevented by oral supplementation with potassium chloride or preferably by the addition of a potassium-retaining diuretic, such as a spironolactone or triamterene. Other side effects of thiazides include reduction of the excretion of uric acid, which may lead to hyperuricemia, and impaired glucose tolerance, which rarely may precipitate hyperosmolar coma in poorly regulated diabetic patients. Skin rashes, thrombocytopenia, and granulocytopenia have also been reported.


This quinethazone derivative has a site of action and potency similar to those of the thiazides but has been reported to be effective in the presence of moderate renal failure. The usual dose is 5 to 10 mg/d. Metolazone may be added to thiazide and loop diuretics in severe HF.

Furosemide, Bumetanide, Ethacrynic Acid, Piretanide, and Torsemide

These "loop" diuretics are similar physiologically but differ chemically from one another. These drugs reversibly inhibit the reabsorption of sodium, potassium, and chloride in the thick ascending limb of Henle's loop, apparently by blocking a cotransport system in the luminal membrane. They may induce renal cortical vasodilatation and can produce rates of urine formation that may be as high as one-fourth of the glomerular filtration rate. Metabolic alkalosis may be caused by a large increase in the urinary excretion of chloride, hydrogen, and potassium ions. Hypokalemia, hyperuricemia, and hyperglycemia are observed occasionally, as with thiazide diuretics. The reabsorption of free water is decreased. All five of these drugs are readily absorbed orally, are excreted in the bile and urine, and are usually effective both intravenously and by mouth. Weakness, nausea, and dizziness may complicate the administration of all loop diuretics; ethacrynic acid has been associated with transient or even permanent deafness as well as with skin rash and granulocytopenia.

These powerful diuretics are useful in all forms of HF, particularly in patients with otherwise refractory HF and pulmonary edema. They have been shown to be effective in patients with hypoalbuminemia, hyponatremia, hypochloremia, hypokalemia, and with reductions in the glomerular filtration rate and to produce a diuresis in patients in whom thiazide diuretics and aldosterone antagonists, alone and in combination, are ineffective. In patients with refractory HF, the action of loop diuretics may be potentiated by intravenous administration and by the addition of other diuretics, i.e., thiazides, metozalone, osmotic diuretics, and the potassium-sparing diuretics-spironolactone, triamterene, and amiloride.

Aldosterone Antagonists

These agents act on the cortical collecting ducts, are relatively weak, and therefore are rarely indicated as sole agents. However, their potassium-sparing properties make them particularly useful in conjunction with the more potent kaliuretic agents, i.e., the loop diuretics, thiazides, and metozalone. The potassium-sparing agents fall into two classes.

The spironolactones resemble aldosterone structurally and act by competitive inhibition of aldosterone, thereby blocking the exchange between sodium and both potassium and hydrogen in the distal tubules and collecting ducts. These agents produce a sodium diuresis, and in contrast to the thiazides, ethacrynic acid, and furosemide, they result in potassium retention. Although secondary hyperaldosteronism exists in some patients with congestive HF, the spironolactones are effective even in patients in whom the serum aldosterone concentration is within normal limits.

Spironolactone may be administered in doses of 25 mg daily to 50 mg three to four times daily by mouth. The maximal effect of this regimen is not observed for approximately 4 days. Spironolactones are most effective when administered in combination with loop and/or thiazide diuretics. The opposing action of these drugs on urine and serum potassium makes possible a sodium diuresis without either hyper- or hypokalemia when spironolactone and one of these other agents are administered in combination. Also, since spironolactone, triamterene, and amiloride act on the distal tubule, they are particularly effective when used in combination with one of these other diuretics that act more proximally. Spironolactone, triamterene, and amiloride should not be administered alone to patients with hyperkalemia, renal failure, or hyponatremia. Reported complications of Aldactone A include nausea, epigastric distress, mental confusion, drowsiness, gynecomastia, and erythematous eruptions.

As mentioned above, a lower dose of spironolactone (25 mg/d), which exerts little if any diuretic effect, has been shown to prolong life in patients with advanced HF (Table 232-3).

Triamterene and amiloride exert renal effects similar to those of the spironolactones; i.e., they block sodium reabsorption and secondarily inhibit potassium secretion in the distal tubules. However, their action does not depend on the presence of aldosterone. The effective dose of triamterene is 100 mg once or twice daily, and that of amiloride is 5 mg daily. Side effects include nausea, vomiting, diarrhea, headache, granulocytopenia, eosinophilia, and skin rash. Both triamterene and the chemically unrelated diuretic amiloride resemble Aldactone A in that their diuretic potency is not great, but they are effective in preventing the hypokalemia characteristic of loop diuretics and thiazides. A number of diuretic preparations contain a combination of a thiazide and either triamterene or amiloride in a single capsule. They may be useful in patients who develop hypokalemia with a thiazide but should not be used in patients with impaired renal function and/or hyperkalemia.

When choosing a diuretic, orally administered loop diuretics or thiazides are the agents of choice in the treatment of chronic cardiac edema of mild to moderate degree in patients without hyperglycemia, hyperuricemia, or hypokalemia. Spironolactones, triamterene, and amiloride are not potent diuretics when used alone, but they potentiate the thiazide and loop diuretics. Loop diuretics, given alone or with spironolactone or triamterene, are the agents of choice in patients with severe HF refractory to other diuretics. In very severe HF, the combination of a loop diuretic, a thiazide, and a potassium-sparing diuretic is required.


Direct vasodilators may be useful in patients with severe, acute HF who demonstrate systemic vasoconstriction despite ACE inhibitor therapy. The ideal vasodilator for the treatment of acute HF should have a rapid onset and brief duration of action when administered by intravenous infusion; sodium nitroprusside (0.1 to 3.0 0x0003bcg/kg per minute) qualifies as such a drug, but its use requires careful monitoring of the arterial pressure and, if possible, of the pulmonary artery wedge pressure. The combination of hydralazine (up to 300 mg qd orally) and isosorbide diuretics (up to 160 mg qd orally) may be useful for chronic oral administration.

Enhancement of Myocardial Contractility


The improvement of myocardial contractility by means of cardiac glycosides is useful in the control of HF. Digoxin, which has a half-life of 1.6 days, is filtered in the glomeruli and secreted by the renal tubules. Significant reductions of the glomerular filtration rate reduce the elimination of digoxin and, therefore, may prolong digoxin's effect, allowing it to accumulate to toxic levels. In patients with normal renal function, a plateau concentration in the blood and tissue is reached after 5 days of daily maintenance treatment without a loading dose (see Fig. 70-2).

Mechanism of Action

The most important effect of digitalis on cardiac muscle is to shift its force-velocity relation upward (Fig. 231-5, p. 1313). Cardiac glycosides inhibit the monovalent cation transport enzyme-coupled Na+,K+-ATPase and increase intracellular sodium content; this, in turn, increases intracellular Ca2+ through a Na+-Ca2+ exchange carrier mechanism. The increased myocardial uptake of Ca2+ augments Ca2+ released to the myofilaments during excitation and, therefore, invokes a positive inotropic response.

Cardiac glycosides also produce alterations in the electrical properties of both the contractile cells and the specialized automatic cells, leading to increased automaticity and ectopic impulse activity. They also prolong the effective refractory period of the atrioventricular node and thereby slow ventricular rate in atrial flutter and fibrillation.

Use in Heart Failure

Digitalis is particularly effective in patients with systolic HF complicated by atrial flutter and fibrillation and a rapid ventricular rate, who benefit from both slowing of the ventricular rate and the positive inotropic effect. Although digitalis does not improve survival in patients with systolic HF and sinus rhythm, it reduces the need for hospitalization. By stimulating myocardial contractility moderately, digitalis improves ventricular emptying; i.e., it increases cardiac output, augments the ejection fraction, promotes diuresis, and reduces the elevated diastolic pressure and volume and the end-systolic volume of the failing ventricle. This action reduces symptoms resulting from pulmonary vascular congestion and elevated systemic venous pressure. Digitalis is of little or no value in patients with HF, sinus rhythm, and the following conditions: hypertrophic cardiomyopathy, myocarditis, mitral stenosis, chronic constrictive pericarditis, and any form of diastolic HF.

The maintenance dose of digoxin is 0.25 mg qd for most adults; in the elderly and others with mild impairment of renal function, it is 0.125 mg qd. Loading doses, four times the maintenance dose, may be administered in acute systolic failure.

Digitalis Intoxication

This is a serious and potentially fatal complication. Advanced age, acute myocardial infarction or ischemia, hypoxemia, magnesium depletion, renal insufficiency, hypercalcemia, electrical cardioversion, and hypothyroidism all may reduce tolerance to digitalis. The most common precipitating cause of digitalis intoxication, however, is depletion of potassium stores, which often occurs in patients with HF as a result of diuretic therapy and secondary hyperaldosteronism.

Anorexia, nausea, and vomiting are among the earliest signs of digitalis intoxication. The most frequent disturbances of cardiac rhythm are ventricular premature beats, bigeminy, ventricular tachycardia, and, rarely, ventricular fibrillation. Atrioventricular block of varying degrees of severity may occur. Nonparoxysmal atrial tachycardia with variable atrioventricular block is characteristic of digitalis intoxication. Chronic digitalis intoxication may be insidious in onset and characterized by exacerbations of HF, weight loss, cachexia, neuralgias, gynecomastia, yellow vision, and delirium.

The administration of quinidine, verapamil, amiodarone, and propafenone to patients receiving digoxin raises the serum concentration of the latter by reducing both the renal and nonrenal elimination of digoxin and by reducing its volume of distribution. These drugs increase the propensity to digitalis intoxication, and the dose of digitalis should be reduced by half in patients receiving these drugs.

Treatment of Digitalis Intoxication

When tachyarrhythmias result from digitalis intoxication, withdrawal of the drug and treatment with 0x0003b2-adrenoceptor blocker or lidocaine are indicated. If hypokalemia is present, potassium should be administered cautiously and by the oral route. Fab fragments of purified, intact digitalis antibodies are a potentially lifesaving approach to the treatment of severe intoxication.

Sympathomimetic Amines

Two sympathomimetic amines that act largely on 0x0003b2-adrenergic receptors-dopamine and dobutamine-improve myocardial contractility (Table 72-1) and are effective in the management of HF; they must be administered by constant intravenous infusion for up to 1 week and are useful in patients with intractable, severe HF, particularly those with a reversible component, such as exists in patients who have undergone cardiac surgery, in patients with acute myocardial infarction and shock or pulmonary edema, and in patients with refractory HF as a "bridge" to transplantation. While these sympathomimetic amines improve the hemodynamics and symptoms in these conditions, it is not clear that they improve survival. Their administration should be accompanied by careful and continuous monitoring of the electrocardiogram, arterial pressure, and, if possible, pulmonary artery wedge pressure.

Dopamine is a naturally occurring immediate precursor of norepinephrine and has a combination of actions that makes it particularly useful in the treatment of a variety of hypotensive states of HF. At very low doses, i.e., 1 to 2 (0x0003bcg/kg)/min, it dilates renal and mesenteric blood vessels through stimulation of specific dopaminergic receptors, thereby augmenting renal and mesenteric blood flow and sodium excretion. In the range of 2 to 10 (0x0003bcg/kg)/min, dopamine stimulates myocardial 0x0003b21 receptors but induces relatively little tachycardia, while at higher doses it also stimulates 0x0003b1-adrenergic receptors and elevates arterial pressure.

Dobutamine is a synthetic catecholamine that acts on 0x0003b21, 0x0003b22, and 0x0003b1receptors. It exerts a potent inotropic action, has only a modest cardioaccelerating effect, and lowers peripheral vascular resistance, but since it simultaneously raises cardiac output, it may not lower systemic arterial pressure in patients with severe HF. Dobutamine, given in continuous infusions of 2.5 to 10 (0x0003bcg/kg)/min, is useful in the treatment of acute HF without hypotension.

A major problem with sympathomimetics is the loss of responsiveness, apparently due to "downregulation" of adrenergic receptors, which becomes evident within 8 h of continuous administration. This problem may be managed by intermittent therapy.

Phosphodiesterase Inhibitors

These bipyridines, amrinone and milrinone, are noncatecholamine, nonglycoside agents that exert both positive inotropic and vasodilator actions by inhibiting a specific phosphodiesterase. They are suitable for intravenous use only; by simultaneously stimulating cardiac contractility and dilating the systemic vascular bed they reverse the major hemodynamic abnormalities associated with intractable HF. Amrinone and milrinone may be administered for the same conditions in which sympathomimetics are useful and may be employed together with dopamine or dobutamine.

Other Measures


Patients with severe HF are at increased risk of pulmonary emboli secondary to venous thrombosis and of systemic emboli secondary to intracardiac thrombi and should be treated with warfarin. Patients with HF and atrial fibrillation, previous venous thrombosis, and pulmonary or systemic emboli are at especially high risk and should receive heparin followed by warfarin.

Diastolic Heart Failure

The major goal in the treatment of this condition is to eliminate or reduce the causes of diastolic dysfunction, such as ventricular hypertrophy, fibrosis, or ischemia. The second is to reduce pulmonary and/or systemic venous congestion, a major consequence of diastolic dysfunction.

Management of Arrhythmias

Premature ventricular contractions and episodes of asymptomatic ventricular tachycardia are common in advanced HF. Sudden death, presumably due to ventricular fibrillation, is responsible for about one-half of all deaths in this condition. (The remainder are due to failure of the cardiac pump.) The management of arrhythmias should commence with correction of electrolyte and acid-base disturbances (Chaps. 49 and 50), especially diuretic-induced hypokalemia, as well as digitalis intoxication (see above). Treatment with class I antiarrhythmics such as quinidine, procainamide, or flecainide (Chap. 230) is fraught with danger because these drugs are proarrhythmic in patients with HF. Amiodarone, a class III antiarrhythmic, on the other hand, is well tolerated and is the drug of choice for patients with heart failure and atrial fibrillation. Patients who have been resuscitated from sudden death, those with syncope or presyncope due to ventricular arrhythmias, and those with asymptomatic ventricular tachyarrhythmias in whom ventricular tachycardia can be induced during electrophysiologic testing should be considered for the implantable automatic defibrillator. This may prevent recurrence of the arrhythmia and sudden death; back-up pacing may prevent sudden death due to bradyarrhythmias.

Refractory Heart Failure

When the response to ordinary treatment is inadequate, HF is considered to be refractory. Before assuming that this condition simply reflects advanced, terminal, myocardial depression, careful consideration must be given to several possibilities: (1) an underlying and overlooked cause of the heart disease that may be amenable to specific surgical or medical therapy, such as infective endocarditis, hypertension, thyrotoxicosis, or silent aortic or mitral stenosis; (2) one or a combination of the precipitating causes of HF, such as pulmonary or urinary tract infection, recurrent pulmonary emboli, arterial hypoxemia, anemia, or arrhythmia; and (3) complications of overly vigorous therapy, such as digitalis intoxication, hypovolemia, or electrolyte imbalance. Recognition and proper treatment of the aforementioned complications are likely to restore responsiveness to therapy.

Hyponatremia is a manifestation of advanced refractory HF. It may be a complication of overaggressive diuresis leading to reduced glomerular filtration rate and decreased delivery of NaCl to the diluting sites in the distal tubule. Hyponatremia may also result from nonosmotic stimuli for the continued secretion of antidiuretic hormone. Therapy involves improvement of the cardiovascular status, if possible (sometimes requiring the administration of a sympathomimetic amine), as well as temporary cessation of diuretic therapy and restriction of oral water intake. Hypertonic saline is very rarely indicated because total-body sodium is usually elevated, not depressed, in HF.

The combination of the intravenously administered vasodilator sodium nitroprusside, a phosphodiesterase inhibitor (amrinone or milrinone), together with a sympathomimetic amine (dopamine or dobutamine) often results in additive effects, raising cardiac output and lowering filling pressure.

In hospitalized patients with refractory HF, therapy guided by hemodynamic measurements provided by a balloon flotation (Swan-Ganz) catheter may be helpful. The goal of manipulating diuretics, vasodilators, and inotropic agents is to achieve a pulmonary capillary wedge pressure of 15 to 18 mmHg, a right atrial pressure of 5 to 8 mmHg, a cardiac index > 2.2 (L/min)/m2, and a systemic vascular resistance of 800 to 1200 dyne ⋅ s/cm5. Once these values are achieved, an attempt should be made to convert the patient from intravenous to oral vasodilator therapy.

Assisted Circulation/Cardiac Transplantation

When patients with HF become unresponsive to a combination of all the aforementioned therapeutic measures, are in New York Heart Association class IV, and are deemed unlikely to survive 1 year, they should be considered for temporary assisted circulation and/or cardiac transplantation (see Chap. 233).

Treatment of Acute Pulmonary Edema

Pulmonary edema secondary to left ventricular failure or mitral stenosis is described in Chap. 32. It is life-threatening and must be considered a medical emergency. As is the case for the more chronic forms of HF, in the treatment of pulmonary edema, attention must be directed to identifying and removing any precipitating causes of decompensation, such as an arrhythmia or infection. However, because of the acute nature of the problem, a number of additional nonspecific measures are necessary. If it does not delay treatment unduly, recording pulmonary vascular pressures through a Swan-Ganz catheter and intraarterial pressure directly is advisable. The first six measures listed below are ordinarily applied simultaneously or nearly so.

1.      Morphine is administered intravenously repetitively, as needed, in doses from 2 to 5 mg. This drug reduces anxiety, reduces adrenergic vasoconstrictor stimuli to the arteriolar and venous beds, and thereby helps to break a vicious cycle. Naloxone should be available in case respiratory depression occurs.

2.      Because the alveolar edema interferes with O2 diffusion resulting in arterial hypoxemia, 100% O2 should be administered, preferably under positive pressure. The latter increases intraalveolar pressure, reduces transudation of fluid from the alveolar capillaries, and impedes venous return to the thorax, reducing pulmonary capillary pressure.

3.      The patient should be maintained in the sitting position, with the legs dangling along the side of the bed, if possible, which tends to reduce venous return.

4.      Intravenous loop diuretics, such as furosemide or ethacrynic acid (40 to 100 mg) or bumetanide (1 mg), will, by rapidly establishing a diuresis, reduce circulating blood volume and thereby hasten the relief of pulmonary edema. In addition, when given intravenously, furosemide also exerts a venodilator action, reduces venous return, and thereby improves pulmonary edema even before the diuresis commences.

5.      Afterload reduction is achieved with intravenous sodium nitroprusside at 20 to 30 0x0003bcg/min in patients whose systolic arterial pressures exceed 100 mmHg.

6.      Inotropic support should be provided by dopamine or dobutamine as described on p. 1327. Patients with systolic HF who are not receiving digitalis should receive 0.75 to 1.0 mg digoxin intravenously over 15 min.

7.      Sometimes, aminophylline (theophylline ethylenediamine), 240 to 480 mg intravenously, is effective in diminishing bronchoconstriction, increasing renal blood flow and sodium excretion, and augmenting myocardial contractility.

8.      If the above-mentioned measures are not sufficient, rotating tourniquets should be applied to the extremities.

After these emergency measures have been instituted and the precipitating factors treated, the diagnosis of the underlying cardiac disorder responsible for the pulmonary edema must be established, if it is not already known. After stabilization of the patient's condition, a long-range strategy for prevention of future episodes of pulmonary edema must be established, and this may require surgical treatment.


The prognosis in patients with HF depends primarily on the nature of the underlying heart disease and on the presence or absence of a precipitating factor that can be treated. When one of the latter can be identified and removed, the outlook for immediate survival is far better than if HF occurs without any obvious precipitating cause. In the latter situation, survival usually ranges between 6 months and 4 years depending on the severity (Fig. 232-2). The long-term prognosis is more favorable when the underlying forms of heart disease, e.g., valvular heart disease, can be treated effectively. The prognosis can be estimated by observing the response to treatment. When clinical improvement occurs with only modest dietary sodium restriction and small doses of diuretics, the outlook is far better than if, in addition to these measures, intensive diuretic therapy and vasodilators are necessary. Other factors that have been shown to be associated with a poor prognosis include a severely depressed ejection fraction (<25%), a reduced maximal O2 uptake [<10 (mL/kg)/min], the inability to walk on the level and at a normal pace for more than 3 min, reduced (<133 mEq/L) serum sodium concentration, reduced (<3 mEq/L) serum potassium concentration, elevated circulating atrial and brain natriuretic peptide and norepinephrine concentrations, as well as frequent ventricular extrasystoles. A large fraction of patients with HF die suddenly, presumably of ventricular fibrillation. Unfortunately, there is no evidence that this complication can be prevented by the administration of antiarrhythmic agents. See guideline material, Table 232-4.

Figure 232-2

Figure 232-2: The natural history of congestive heart failure (CHF). Once left ventricular systolic dysfunction is present, it usually progresses, albeit not predictably. As left ventricular dysfunction progresses and symptoms increase, mortality rate increases and the process becomes inexorable. Myocyte loss and fibrosis become irreversible. An effective preventive measure must be introduced before onset or early in the course of progressive left ventricular dysfunction.