4. Heart failure
- Definition and background. During the past two decades, new fundamental knowledge and a number of new therapies have become available that have changed the way congestive heart failure (CHF) is approached. For example, a number of multicenter trials have shown that the addition of vasodilator therapy to digoxin and diuretics significantly improves 1-year survival in patients with CHF. Despite these new modalities, mortality from CHF remains high. Moreover, CHF is often a disease of older individuals who represent the most rapidly growing segment of the American population. Consequently, CHF has become one of the most common admission diagnoses for acute care hospitals.
On the most fundamental level, heart failure represents the failure of the heart to supply adequate blood flow and, hence, nutrients and oxygen to metabolizing tissues. The underlying reasons for heart failure are often complex, and the physiologic basis is incompletely understood; however, all forms of heart failure can ultimately be traced to the relative or absolute failure of the heart as a pump. This inadequate cardiac function sets off a series of compensatory actions that eventually do more harm than good; that is, they "overcompensate" by causing the body to retain salt and water, thereby leading to edema formation. The abnormally active compensatory actions involve the sympathetic nervous system, the renin-angiotensin system, and antidiuretic hormone released from the pituitary gland. Decreased cardiac output combined with pulmonary and peripheral edema results in effort intolerance. As heart failure progresses, various cytokines are activated. Tumor necrosis factor appears to play an important role in the fatigue, skeletal muscle atrophy, and eventual cachexia that affects patients with severe CHF.
A patient with heart failure usually has one or more symptoms (e.g., fatigue, dyspnea, orthopnea, paroxysmal nocturnal dyspnea [PND]) and a variety of physical signs (e.g., pulmonary rales, gallop rhythms, peripheral edema). The problems faced by the clinician in the diagnosis of heart failure are threefold: (i) differentiating heart failure from other conditions that may mimic it, (ii) identifying underlying cardiac disease, and (iii) determining any precipitating cause. True cardiac failure always implies some form of underlying heart disease. Although almost any type of cardiac disease can lead to cardiac failure, the most common cardiac etiologies are listed in Table 4-1. The diagnostic problem is complicated by the fact that many forms of cardiac disease present as cardiac failure without prior symptoms.
Major precipitating causes of cardiac failure are shown in Table 4-2. A careful and systematic search for these precipitants should be undertaken in all patients presenting with cardiac failure. The search for precipitating causes assumes particular importance in patients whose initial presentation is one of cardiac failure, in patients with known cardiac disease who suffer acute deterioration, and in patients who fail to respond to conventional therapies.
- Types of heart failure. Various terms have been used to describe subsets of patients with heart failure. Many of these terms are either self-explanatory (acute heart failure vs. CHF) or disputed (forward vs. backward heart failure). Two frameworks for categorizing heart failure, however, should be noted:
- High-output versus low-output heart failure. Although the range of "normal" cardiac output is large, certain types of heart failure tend to involve higher output states, whereas others display low cardiac outputs. High output is associated with arteriovenous fistula, Paget's disease, anemia, and hyperthyroidism. Although the term high output is often used to describe these conditions, a more correct term should be high, but not high enough, cardiac output. This latter statement emphasizes the fact that the cardiac output may be surprisingly normal in patients with arteriovenous fistula, Paget's disease, anemia, or hyperthyroidism, but it is not sufficient to supply the peripheral demand for blood flow given the marked decrease in peripheral vascular resistance and/or increased metabolic demand of the peripheral tissues.
Typical low-output states include hypertension, coronary artery disease, and the cardiomyopathies.
- Right-sided versus left-sided heart failure. The clinical presentation of heart failure may vary depending on which ventricle is more affected. Pressure increases behind the more affected chamber result in transudation of fluid. In right-sided failure, hepatic congestion and its attendant symptoms occur; when left-sided failure predominates, pulmonary congestion and its attendant symptoms assume more prominence. In long-standing or severe heart failure, both ventricles are dysfunctional, and these distinctions become blurred.
- Pathophysiology. The underlying pathophysiology of heart failure remains the object of intense research. It appears that abnormal release and reuptake of intracellular calcium from the sarcoplasmic reticulum is one of the central pathophysiologic mechanisms operating in CHF. For the clinician, one aspect of the pathophysiology of heart failure remains foremost: Is the observed episode of CHF based on a primary failure of the contractile function of the heart muscle itself (e.g., ischemia or infarction), or is it the result of the myocardium's inability to respond to an altered external condition (such as valve rupture or acute hypertensive crisis)? This fundamental distinction dramatically alters the therapy that is selected.
- History. Significant items in the history of patients with heart failure are presented in Table 4-3. The most commonly quoted symptoms in patients with heart failure are the triad of respiratory complaints: dyspnea, orthopnea, and PND.
- Dyspnea. Dyspnea represents the most prevalent and often the earliest symptom of heart failure. The sense of shortness of breath arises from the increased effort of breathing that accompanies heart failure. It is particularly common when left ventricular failure predominates: Left atrial and ultimately pulmonary venous pressures rise, and fluid transudes into the pulmonary interstitium, thereby reducing pulmonary compliance. A history of the activities that provoke dyspnea is important. Typically, dyspnea occurs with progressively smaller amounts of exercise and finally develops at rest as CHF worsens. Patients often unconsciously restrict their activity to avoid this unpleasant sensation, and they should be questioned closely concerning effort intolerance.
- Orthopnea. Orthopnea is said to be present when the patient breathes more comfortably with the upper part of the body elevated rather than in recumbent position. In severe heart failure, patients may spend the entire night sleeping in a chair to maintain this elevation.
- PND. PND refers to episodes of severe shortness of breath, often occurring at night and, in contrast to orthopnea, frequently not relieved by sitting upright. PND is one of the most specific symptoms of left-sided heart failure.
Other respiratory symptoms that can accompany heart failure include cardiac asthma and Cheyne-Stokes respiration. Wheezing from cardiac asthma results, at least in part, from bronchial edema caused by transudated fluid. Patients who have bronchospasm for other reasons appear more susceptible to cardiac asthma. The symptoms of cardiac asthma are sometimes difficult to distinguish from those arising secondary to bronchial asthma or bronchitis. Cheyne-Stokes respiration (also called cyclic respiration) is recognized as periods of hyperpnea followed by periods of apnea. This abnormal pattern of breathing often occurs in patients with cerebral atherosclerosis and low cardiac output. Other items to emphasize in the history of the present illness deal directly with possible acute precipitating events. The ten most common precipitating events that lead to heart failure are listed in Table 4-2. These events should be considered in any patient with heart failure of unknown etiology. All patients who present with heart failure should have a complete cardiac history to uncover possible underlying cardiac disease. Current medications and diet should also be discussed. Patients frequently are confused concerning medication schedules and dietary restrictions, and compliance with medication regimens and/or dietary restrictions (e.g., salt) is often a problem.
- Physical examination. Physical findings of heart failure are listed in Table 4-4. The overall condition of a patient in heart failure varies according to the degree of cardiac dysfunction present. Physical findings may be divided into two large categories: (i) findings within the cardiovascular system itself and (ii) findings in other organ systems resulting from heart failure.
- Cardiovascular findings in heart failure. Gallop sounds are common in heart failure. A ventricular gallop (S3), which may be normal in some populations (children and young adults), is the result of a marked compliance change in the left ventricle. Left ventricular gallops are best heard at the apex with the bell of the stethoscope; right ventricular gallops are best heard in the subxiphoid region or over the right ventricle. Atrial gallops (S4) may also be heard in heart failure, although this finding is much less specific. A sustained left ventricular lift or evidence of cardiac enlargement (dilatation) may be discovered by palpation. A brisk but unsustained left ventricular lift is characteristic of patients with high-output failure (e.g., hyperthyroidism anemia). A more sustained lift is associated with hypertensive heart disease and aortic stenosis. Both systolic and diastolic murmurs can be heard in specific conditions. Neck veins should be examined for evidence of elevated central venous pressure. The presence of hepatojugular reflux should be ascertained because this finding has excellent correlation with elevation of the pulmonary capillary wedge (PCW) pressure.
- Findings caused by the effect of heart failure on other organ systems. Pulmonary rales may be found at varying levels in both lung fields. Bronchial wheezing may be present on the basis of heart failure alone. Liver engorgement from right-sided heart failure may lead to tender hepatomegaly. Resultant liver dysfunction can eventually lead to jaundice and ascites. Transudation of fluid into the extracellular space may produce peripheral edema (particularly in dependent extremities) or pleural effusions. A patient who has been bedridden should be checked for sacral edema.
- Laboratory tests. The diagnosis of heart failure is usually based on clinical criteria. Recently, elevated levels of brain natruretic peptide (BNP) have been observed in patients with CHF. The degree of elevation of plasma BNP levels correlates well with the severity of CHF. Because of these observations, some authorities have argued that a diagnosis of CHF should not be made unless the patient has an elevated plasma BNP level. Much work remains to be done in this arena, and consequently, most cardiologists are not ready to accept BNP determination as the gold standard for the diagnosis of CHF. Certain basic laboratory work should be performed in all patients with heart failure; other laboratory studies are made when specific diagnoses are suspected. All patients should have the following blood tests: complete blood cell count, electrolytes, blood urea nitrogen (BUN), creatinine, and urinalysis. Liver function tests may be added when hepatomegaly is present on examination, although the pattern of abnormality is likely to be nonspecific in hepatic congestion.
- ECG. No ECG findings are specific for heart failure. An ECG should be obtained, however, to look for both signs of possible underlying cardiac disease (signs of ischemia, left ventricular hypertrophy, right ventricular hypertrophy, rhythm disturbances) and signs of acute precipitating events (QRS evidence of myocardial infarction; S1,Q3,T3 of pulmonary embolism). An initial ECG also provides baseline data for comparison with future ECGs.
- Chest x-ray examination. Radiologic signs of heart failure are important, often subtle, and, in the early stages of CHF, frequently missed. The earliest radiographic sign of heart failure may be pulmonary venous hypertension caused by elevated left-sided filling pressures (pulmonary vascular redistribution, dilatation of the pulmonary artery). As pulmonary vascular pressure continues to rise, interstitial edema develops with thickening of interlobar fissures (in the lower lung fields, these are called Kerley B lines; similar longer lines in the upper and mid lung fields are termed Kerley A lines). Subpleural fluid and free pleural fluid also may accumulate at this stage. Any or all of these findings may precede the classic x-ray finding of the "butterfly" pattern of alveolar pulmonary edema.
- Echocardiography. An echocardiographic study does make the diagnosis of CHF, despite the fact that ventricular dysfunction is observed. Clinical signs and symptoms must be present to make the clinical diagnosis of CHF. However, echocardiographic studies are extremely useful in patients with CHF because these studies help to establish the diagnosis of any underlying form of heart disease. Thus, echocardiography is helpful if valvular, congenital, or ischemic heart disease is thought to underlie heart failure. In addition, echocardiographic evaluation of left ventricular function may be determined serially to assess the effect of therapy.
- Radionuclide studies. Radionuclide studies are often useful for detecting congenital defects, left ventricular wall motion abnormalities, and ventricular aneurysms, all of which may underlie heart failure (see Chapter 2).
- Catheterization and angiography. Cardiac catheterization can aid in the diagnosis of heart failure. Hemodynamic measurements reveal elevated left and/or right ventricular filling pressures in patients with CHF. Angiography helps in defining heart disease that may be the cause of CHF, for example, critical coronary artery disease. Catheterization may also be used to help assess the therapeutic efficacy of various pharmacological agents used in patients with severe forms of heart failure.
- Protocol for the diagnosis of heart failure
- Confirmatory tests needed to make the diagnosis. The diagnosis is suggested by observation of a combination of the symptoms and signs previously discussed. Further support for the diagnosis of heart failure is derived from the demonstration of an underlying cardiac disease (Table 4-1). The protocol for establishing the diagnosis in each of the underlying cardiac diseases is outlined in appropriate chapters in this book. A general protocol for establishing the diagnosis of heart failure is outlined in Table 4-5.
- Differential diagnosis. Other diseases that present with signs or symptoms mimicking those of heart failure are listed in Table 4-6.
- Pulmonary disease. In some situations, the distinction between underlying cardiac or pulmonary disease in a dyspneic patient may be difficult to make. Diagnostic problems are further complicated when the diseases coexist. In general, dyspnea secondary to pulmonary disease develops more gradually than does dyspnea based on cardiac dysfunction. An important exception occurs when a patient with underlying pulmonary disease develops an acute pulmonary infection in which onset of dyspnea may be extremely rapid. Quantity and characteristics of sputum production must be assessed. Other signs of infection (fever, elevated white blood cell count, and left-shifted differential) should be sought. Patients with long-standing asthma or chronic bronchitis are more susceptible to wheezing and bronchoconstriction if left ventricular failure occurs (so-called cardiac asthma) compared with patients without pulmonary disease. Cardiac asthma generally produces more diaphoresis and cyanosis than does a primary asthmatic attacks; however, the distinction is often hard to draw. After resolution of the acute process, pulmonary function studies may help define the extent of underlying lung dysfunction.
- Noncardiac causes of peripheral edema. Occasionally, confusion arises over the etiology of ankle edema. Although cyclic edema and peripheral venous disease may cause ankle swelling, dyspnea and increased systemic venous pressure will be absent. Careful chest and neck vein examination should resolve any question. It is important to check for peripheral edema bilaterally to rule out unilateral edema from venous blockage or trauma.
- Other noncardiac causes of edema. The possibility of renal dysfunction as the cause of underlying edema may be suggested by a history of renal disease.
Initial blood studies (BUN, creatinine, calcium, phosphate, and total protein) and urinalysis (proteinuria, hematuria, casts) will help confirm or exclude renal disease. Edema from cirrhosis may be suggested by history (alcoholism), physical examination (jaundice, spider angiomas, other peripheral stigmata of liver disease), and laboratory studies (total and direct bilirubin, serum glutamic oxaloacetic transaminase, lactic acid dehydrogenase, alkaline phosphatase levels).
- Therapy. There are three major aspects of the treatment of heart failure: (i) management of the acute or chronic condition, (ii) treatment of any underlying cardiac disease, and (iii) treatment of any precipitating factor. The treatment of cardiac diseases that can cause heart failure (Table 4-1) is discussed in chapters on each disease. Precipitating causes of heart failure (Table 4-2) should be corrected. For example, patients with hematocrits less than 30% should receive blood transfusions of packed red blood cells and diuretics; individuals with pneumonia should receive appropriate antibiotics, etc.
- Medical therapy. Medical modalities for the treatment of heart failure seek to improve overall cardiac function while removing excess salt and water that has accumulated. The classic view of ventricular function is summarized in the Frank-Starling relationship between cardiac muscle fiber length and strength of contraction (Fig. 4.1).
Fig. 4-1. Schematic Frank-Starling curves for patients with heart failure indicating the effect of therapy.
The hearts of patients with heart failure operate on depressed ventricular function curves or from a disadvantageous position on a normal function curve. A number of interventions can improve ventricular function.
Inotropic agents augment myocardial contractility and establish a more favorable function curve. Sympathomimetic agents such as dopamine and dobutamine may act through both inotropic augmentation and afterload reduction. Arterial vasodilators allow the dysfunctioning heart to operate on a more normal Starling curve. Diuretics and venodilators (e.g., nitrates) act by reducing central blood volume and hence cardiac dilatation, thus achieving a more favorable position on the same ventricular function curve. Three basic types of pharmacologic therapy are available to improve ventricular function in heart failure: (i) agents that decrease excessive retention of fluid (move to the left on the Frank-Starling curve), (ii) agents that augment myocardial contraction (establishment of new Starling curve), and (iii) agents that decrease cardiac work load.
- Decrease of excessive fluid retention. Diuretics are the main treatment for fluid retention. In general, these agents should be used in conjunction with vasodilators and, at times, digitalis along with modifications in dietary salt intake and activity.
The choice of diuretic or combination of diuretics used in heart failure depends largely on the severity of the clinical situation. If fluid retention is mild, no treatment or an oral diuretic is used. When used alone, potassium-sparing diuretics (spironolactone and triamterene) generally are less effective than are thiazides; however, these two agents potentiate other diuretics (furosemide and ethacrynic acid) and are thus effective when used in combination with other agents. Spironolactone is particularly advantageous in this regard because it has been shown to reduce mortality in patients with CHF. The loop diuretics (furosemide and ethacrynic acid) are the agents of choice in severe heart failure. A general approach to the use of diuretics in heart failure is outlined in Table 4-7. Dietary and activity recommendations are discussed in later sections.
- Spironolactone (Aldactone). The addition of spironolactone to thiazide or loop diuretics has been a long-standing recommendation for patients with severe CHF. In recent years, multicenter trials have demonstrated decreased morbidity and mortality when spironolactone is used in patients with CHF. Consequently, 25 to 50 mg of spironolactone once or twice per day is now commonly prescribed for patients with moderate or severe CHF. Careful monitoring of renal function and electrolytes is required since these patients are commonly also treated with angiotensin-converting enzyme (ACE) inhibition or angiotensin receptor blockade. The combination of blockade of the renin angiotensin system together with spironolactone can result in renal insufficiency and/or life-threatening hyperkalemia.
- Decrease of cardiac workload. Vasodilators reduce the impedance (resistance) against which the heart must pump. Although diuretics reduce the preload of the heart and digitalis augments contractility, vasodilators reduce afterload by direct action on the peripheral vascular bed. These agents have been demonstrated to reduce mortality and morbidity in a variety of acute heart failure and CHF states. Specific drugs, dosages, side effects, and contraindications are given in Table 4-8. Vasodilator therapy can be lifesaving in patients with severe, acute heart failure and pulmonary edema secondary to cardiomyopathy or ischemic heart disease. Improvement in cardiac output and relief of congestion may ameliorate dyspnea and cause significant diuresis. Careful monitoring to avoid hypotension is essential in these fragile patients.
Beta-blockers (see below) also decrease cardiac work and can lead to remarkable clinical improvement. Patients with CHF who are treated with long-term beta-blockade often demonstrate remarkable improvement in measured left ventricular function. A number of multicenter trials have demonstrated decreased mortality and morbidity in patients with CHF who are treated with beta-blockers.
- Vasodilator therapy in chronic heart failure. In many patients with CHF, a diagnostic workup including cardiac catheterization demonstrates underlying or precipitating conditions that are not remediable by either specific medical or surgical intervention. These patients can often derive substantial benefit (reduced mortality and morbidity) from therapy that includes vasodilatation with ACE inhibitors or angiotensin receptor blockers, as well as weight loss, sodium-restricted diets, diuretics, beta-blockers, and, at times, digitalis. The combination of nitrates and hydralazine is also effective in this setting, but it is not as efficacious as ACE inhibition or angiotensin receptor blockade (Table 4-8).
- Vasodilator therapy in acute heart failure. A variety of vasodilators have been shown to have beneficial effects in patients with acute heart failure. Both arterial and venous vasodilators are effective. Intravenous vasodilatation with nitroprusside is particularly beneficial in patients with volume overload states, for example, mitral and/or aortic regurgitation. Intravenous forms of ACE inhibitors are also available for this indication. Nitroglycerin and other nitrates fall into the general class of drugs that dilate small venules and thereby increase venous capacitance (venodilators). This reduces central blood volume and cardiac dilatation and results in a reduction in preload and a fall in PCW pressure and left ventricular end diastolic pressure. This is, in effect, an anatomic "diuresis," that allows the ventricle to function on a more favorable point on the Starling curve. Because nitrates also dilate coronary collateral blood vessels, they are particularly useful in patients with acute heart failure secondary to ischemic heart disease. Intravenous nitroglycerin is frequently used in this setting.
- Beta-blockade. Beta-blockers have been shown to reduce mortality and morbidity in patients with CHF. Even patients with severe CHF can benefit from these agents. Patients treated with long-term beta-blockade demonstrate improvement in left ventricular ejection fraction after a number of months of therapy. It is essential that beta-blocker therapy commence with very small doses, for example, 12.5 mg of metoprolol twice a day or 3.25 mg of carvedilol twice a day. Dosage is slowly advanced as tolerated over a number of weeks, aiming for 50 mg of metoprolol bid or 25 mg of carvedilol twice a day. During this up-titration, it may be necessary to increase the dose of diuretics because some patients experience increased fluid retention at this time.
- Augmentation of myocardial contraction. Three types of medication are available to augment myocardial contraction: digitalis preparations, other inotropic agents (amrinone, milrinone), and certain sympathomimetic agents (dopamine, dobutamine). Although amrinone, milrinone, and the sympathomimetic agents also have some vasodilating properties, their primary role is to augment myocardial contraction, and they will be discussed in this section.
- Digitalis. Digitalis increases the contractility of the failing heart (establishes a more advantageous Frank-Starling curve) and increases cardiac output. The multicenter DIG trial (The Digitalis Investigation Group; see Suggested Reading) found that digoxin therapy did not increase or decrease mortality during long-term follow-up in patients with CHF. Hospitalization for heart failure was reduced by digoxin therapy. Digoxin is not as efficacious as vasodilators and diuretics, and hence, it has become a third-line drug for the management of CHF.
The following precautions should be observed before digitalis is administered to a patient: (i) a detailed history should be sought. In addition to the history of cardiac disease and possible precipitating events already discussed, a history of previous use of digitalis is important. Any adverse reaction to previous administration should be carefully explored. History of any renal, pulmonary, hepatic, or thyroid disease also should be ascertained. Knowledge of other current medications is essential, because many medicines interfere with gastrointestinal absorption of digitalis (e.g., antacids, cholestyramine). Concomitant administration of amiodarone or verapamil and digitalis results in higher serum levels (and increased evidence of toxicity) of digitalis than when glycoside is administered alone. (ii) Certain laboratory procedures should be undertaken. Serum electrolytes, creatinine, and BUN should be drawn before digitalis is administered, and electrolyte abnormalities should be corrected. A 12-lead control ECG is essential, because once digitalis has been administered, ischemic changes may be impossible to distinguish from digitalis effects. Serum digitalis levels may be helpful; low levels suggest poor compliance or inadequate gastrointestinal absorption.
- Protocol for administration of digitalis. Various methods have been developed for determining the proper initial dose of digitalis and the appropriate ongoing maintenance dosage. The following general considerations apply: (i) modern physicians only use one digitalis preparation, digoxin. (ii) When rapid digitalization is desired, in an average-sized patient with no body stores of digitalis and normal renal function, 1 mg of oral digoxin over 24 hours in divided doses is recommended. Maintenance dosage for this patient would be 0.125 mg per day by mouth. (iii) When it is not essential to achieve rapid digitalization, the process can be accomplished by a daily maintenance dose without a loading dose. In average-sized patients with normal renal function, 0.125 mg of digoxin per day will allow digitalization within 1 week. (iv) In patients with impaired renal function, the amount of digitalis administered must be appropriately reduced. Calculating creatinine clearance in addition to obtaining serum creatinine may be helpful in this situation.
It is important to remember that other medications may influence the pharmacokinetics of digitalis preparations. Cholestyramine, neomycin, nonabsorbable antacids, and Kaopectate may all decrease absorption of oral digoxin. Quinidine has been shown to decrease both renal and nonrenal elimination of digoxin and to decrease its apparent volume of distribution. When conventional dosages of quinidine are administered, serum digoxin concentrations average a two-fold increase. Thus, digoxin dosage must be reduced appropriately if quinidine is added. Amiodarone, flecainide, and verapamil administration can also raise serum digoxin levels. Thus, when any of these antiarrhythmic agents is introduced, digoxin levels must be closely monitored and dosages adjusted accordingly.
Numerous ECG changes can occur during therapy with digitalis: lengthening of the P–R interval, shortening of the Q–T interval, depression or "scooping" of the S–T segment (or both), and flattening or inversion of T waves.
- Digitalis intoxication. Both noncardiac and cardiac signs of digitalis toxicity may occur. Early noncardiac symptoms include visual changes (yellow vision, blurred vision, diplopia), gastrointestinal complaints (anorexia, nausea, vomiting), and neurologic manifestations (headache, lethargy).
Cardiac evidence of digitalis toxicity may precede noncardiac symptoms. The chief cardiac manifestation is arrhythmia. Almost every cardiac arrhythmia may be provoked by digitalis intoxication except for atrial flutter. Digitalis levels, when available, may assist in the diagnosis of digitalis toxicity. The diagnosis, however, remains clinical and electrocardiographic.
To treat digitalis-induced arrhythmias one should (i) stop digitalis, (ii) measure serum electrolyte levels and correct any abnormalities (particularly hypokalemia), and (iii) if the arrhythmias associated with an episode of digitalis toxicity are serious, administer specific antiarrhythmic drug therapy, for example, intravenous (IV) lidocaine or beta-blockers for malignant ventricular arrhythmias (see Chapter 3 on arrhythmias). When large doses of digoxin are ingested during a suicide attempt, severe digitalis toxicity and life-threatening hyperkalemia often develops. The appropriate therapy in this situation is IV monoclonal antidigitalis antibodies (e.g., Digibind). Clinical information on digoxin is found in Table 4-9.
- Other inotropic agents. IV amrinone and milrinone are positive inotropes and peripheral vasodilators. They cause dose-dependent reductions in both left- and right-heart filling pressures and increases in cardiac output. Systemic and pulmonary vascular resistance are decreased. Amrinone's hemodynamic effects are similar to a combination of dobutamine and nitroprusside. The drug acts synergistically with digoxin and sympathomimetics. Amrinone is useful in patients with heart failure that has been refractory to digoxin, diuretics, and vasodilators. Amrinone is administered with an initial IV bolus of 0.75 mg/kg followed by a continuous infusion of 5 to 10 mcg/kg per minute. Hypotension may be a limiting factor in patients already on a vasodilator. Amrinone is particularly effective in patients with reversible myocardial depression after cardiac surgery and after acute myocardial infarction. Tolerance, a potential problem with combination therapy with dobutamine and nitroprusside, does not appear to occur with amrinone.
- Sympathomimetic amines. A variety of investigations has assessed the utility of sympathomimetic amines and catecholamines in the treatment of heart failure. Investigations using isoproterenol, epinephrine, and norepinephrine have largely failed because of adverse hemodynamic consequences associated with these medicines, such as tachycardia and peripheral vasodilatation or vasoconstriction. Two other sympathomimetic aminesdopamine and dobutaminehave fewer undesirable hemodynamic side effects and are useful in the management of heart failure.
- Dopamine (Intropin). Dopamine is an endogenous catecholamine that is the precursor of norepinephrine. It has beta1 (cardiac stimulatory) activity, alpha activity (peripheral vasoconstricting), and an independent vasodilatory effect (at low dosages) on the renal and mesenteric vascular beds. At low dosages (less than 5 mcg/kg per minute) the beta1 and renal vasodilatory effects predominate. At dosages between 5 and 10 mcg/kg per minute, both alpha and beta stimulation occur. At dosages greater than 10 mcg/kg per minute, alpha peripheral constriction predominates. In decompensated or acute heart failure, dopamine in low dosages (less than 5 mcg/kg per minute) may exert favorable hemodynamic actions by increasing both cardiac output and renal blood flow, thereby promoting a diuresis.
- Dobutamine (Dobutrex). Dobutamine is a synthetic sympathomimetic amine with beta1 (cardiac stimulatory), beta2 (peripheral vasodilatory), and minimal alpha1 (vasoconstricting) effects.
In decompensated heart failure, dobutamine in IV dosages up to 10 mcg/kg per minute exerts favorable hemodynamic effects by improving cardiac output and decreasing PCW pressure and congestive symptoms. Dobutamine is particularly valuable in patients with severe heart failure and an elevated PCW and normal systemic blood pressure.
- Dobutamine versus dopamine. A number of trials have compared dopamine and dobutamine in severe or acutely decompensated heart failure. Both medications will successfully improve cardiac output; however, dobutamine appears more effective in lowering filling pressures and in reducing congestive symptoms. Dopamine may be more effective when the patient is hypotensive or when its independent renal effects are desired. The choice between these two medications ultimately will hinge on the clinical situation in each patient. These medications have been successfully used together with vasodilators for refractory heart failure.
- Combination sympathomimetic amine and vasodilator therapy for refractory heart failure. Refractory heart failure is said to be present when deterioration in the patient's condition occurs despite intensive therapy (see Section III.C.3.d.).
Some individuals with such severe heart failure will benefit from hospitalization in the intensive or coronary care unit and from therapy with a combination of a sympathomimetic amine and a vasodilator. A typical combination is IV dobutamine and nitroprusside, although the combination of dopamine and nitroprusside has been used as well.
- Long-term pharmacologic treatment of severe heart failure. As noted earlier, patients with heart failure should receive ACE inhibitors and beta-blockers if tolerated. Other vasodilators such as angiotensin receptor blockers or hydralazine/nitrate combinations can be used if the patient does not tolerate ACE inhibitors, for example, because of chronic cough.
A number of large trials have demonstrated that daily aspirin decreases long-term morbidity and mortality in patients with CHF. The exact dose of aspirin has not been well studied, but most investigators use 160 to 325 mg per day.
- Activity. Appropriate restriction of physical activity remains a central therapeutic tool in heart failure. For the patient with mild heart failure, slight reduction in cardiac work load (such as resting on weekends, taking a nap in the middle of the day, or slightly reducing the work week) may allow continued gainful employment. In the patient with severe heart failure, periods of bed rest and an overall diminution in activity are essential to lessen cardiac work. In the acute setting of symptomatic heart failure, 1 to 2 weeks of significantly reduced activity is often necessary.
Note that bed rest, particularly in elderly patients, increases the risk of venous thrombosis and pulmonary embolism. Patients are allowed up two or three times daily and are encouraged to remain ambulatory. Once medical therapy has stabilized the patient with CHF, a gentle and progressive exercise program can be beneficial. Such exercise programs are most successful when careful supervision (i.e., a formal cardiac rehabilitation program) is available.
- Diet. Dietary therapy has two aims in the treatment of heart failure. First, any patient who is overweight should be encouraged to lose weight and is given specific advice and guidance on caloric restriction. Weight reduction lowers the demand on the heart and often results in significant symptomatic relief. Second, sodium restriction remains an important component of therapy in heart failure. For the patient with severe heart failure, rigid sodium restriction is essential.
The average daily American diet in the absence of sodium restriction contains 8 to 15 g of salt (1 level teaspoon contains 6 g of salt). A reduction to 4 to 7 g per day can be accomplished by removing the salt shaker from the table. A further reduction to 3 to 4 g can be achieved by restricting salt addition during cooking. Reduction in sodium intake is further accomplished by eliminating high-salt–containing foods from the diet. Foods to be avoided include canned vegetables and soups, as well as processed cheeses, breads, and cereals. Allowable foods include fresh produce, specially processed bread, low-sodium milk, and salt substitutes. Because it is difficult to make a severely sodium-restricted diet palatable, compliance with these regimens is frequently a problem.
- Environment and psychological support. Emotional rest is as important as reduced physical activity for the heart failure patient. Both lessen cardiac work load. Efforts should be made to lower the patient's level of anxiety. In the setting of acute heart failure, mild sedation with a benzodiazepine may be helpful in addition to calm reassurance. The use of morphine in acute pulmonary edema is important not only as a pulmonary vasodilator but also as a sedative to relieve anxiety (see Chapter 5). Long-term psychological support is essential to the patient with heart failure who must face the issues of reduced activity, chronic medication, and a restricted, often unpalatable, diet.
- Surgical treatment. The treatment of CHF can often be managed with medicines, diet, and limitation of activity. In certain situations, however, surgical intervention and/or device implantation is the treatment of choice.
- Cardiac transplantation. The technical capability to perform cardiac transplantation has been available since the late 1960s. High mortality caused by rejection of grafted hearts caused this option to fall into disfavor in the 1970s.
Major advances in the immunologic management of the cardiac transplantation patient has made this a very viable option for some patients with intractable heart failure. At Stanford University after its first 250 heart transplantations, a 1-year survival rate of 82% was reported. Over half the patients operated on at Stanford had myocardial dysfunction based on coronary artery disease; most of the rest had cardiomyopathy from other causes. At the University of Arizona, 1-year survival rates of 90% have been observed. The most important pharmacologic agent for suppressing rejection in transplant patients appears to be cyclosporin A. The transplanted heart lacks normal autonomic innervation; however, it will respond to circulating catecholamines that allow cardiac output to rise during exercise. A small percentage of patients develop reinnervation of the heart with time. These individuals will have a normal increase in heart rate during exercise. Functional rehabilitation is possible in more than 90% of patients successfully transplanted. Currently, cardiac transplantation is performed in many United States centers with considerable success.
- Circulatory assist devices. The intraaortic balloon pump is the most commonly used mechanical circulatory assist device. The intraaortic balloon pump is often successful in stabilizing patients with acute CHF while appropriate medical and/or surgical therapy is instituted. In addition, both temporary and permanent left and/or right ventricular assist devices are being implanted in many cardiac surgical centers in the United States. The power source for these pumps is external to the patient, requiring a chronic transthoracic connection. These indwelling power connections can be a site for serious infections. Some technical problems remain, for example, embolized thrombus from the pump itself, but advances continue in this area. Completely self-sustaining, implantable devices are available, and early clinical work with these high technology instruments has been encouraging.
- Other indications for surgical intervention in heart failure. Pulmonary embolism can be treated by means of embolectomy and/or inferior vena caval interruption or filtration (see Chapter 22). Surgical treatment may be lifesaving when heart failure is precipitated by acute dysfunction of a cardiac valve (ruptured chordae tendineae or acute bacterial endocarditis).
When coronary artery disease with acute ischemic myocardial dysfunction underlies heart failure, coronary bypass surgery is beneficial. Surgical correction is also the treatment of choice in most forms of congenital heart disease complicated by CHF. When left ventricular aneurysm causes heart failure, aneurysmectomy may be necessary. Finally, for patients with chronic CHF caused by an underlying cardiomyopathy, cardiac transplantation should be considered (see above).
- Biventricular pacing. Patient with severe heart failure and left bundle branch block or intraventricular conduction delay with a very wide QRS complex (greater than 0.12 second) should be considered for biventricular pacing therapy. These patients have dis-coordinated ventricular contraction as a result of the marked conduction disturbance. A pacing catheter is placed in the distal coronary sinus. Pacing from this site captures the left ventricle. A second pacing catheter is placed at the apex of the right ventricle. A special biventricular pacemaker induces a more coordinated contraction of the left and right ventricles. This has been shown to increase cardiac output and decrease symptoms in patients with severe CHF.
- Protocols for treatment of heart failure
- Medical management of mild heart failure
- Perform initial history, physical examination, and screening laboratory tests with particular emphasis on the cardiovascular system. Look for possible underlying cardiac disease or precipitating causes of heart failure (Tables 4-1 and 4-2).
- Perform additional laboratory investigations to establish the diagnosis of a specific underlying or precipitating cause of heart failure, for example, echocardiography and/or coronary angiography.
- While the diagnostic workup is in progress, begin symptomatic treatment:
- Diuresis. Initiate a gentle diuresis with oral diuretics at modest dosages, for example, furosemide 20 mg every day in the morning. Monitor electrolytes and renal function.
- ACE inhibitors. Place the patient on modest to moderate doses of an ACE inhibitor if tolerated (Table 4-8). If side effects are a problem with ACE inhibition, for example, chronic cough, try modest to moderate doses of an angiotensin receptor blocker (Table 4-8).
- Beta-blockers. Consider starting the patient on beta-blockade, using small doses initially.
- Diet. Remove salt from table and eliminate foods with high sodium content from diet. Advise weight reduction if obesity is present.
- Activity. Establish a plan with the patient for appropriate temporary reduction in activity. Suggest that the patient purchase a scale and record daily weights and that the patient inform you of sudden weight gain of 3 lbs or more.
- At follow-up appointment in 2 to 4 weeks, check blood pressure, signs of CHF, renal function, and electrolyte levels; obtain an ECG if ischemic heart disease was the underlying cause for CHF.
- Medical management of moderate heart failure
- History, physical examination, initial screening, and additional laboratory investigations looking for underlying and precipitating causes of heart failure; similar to evaluation for mild CHF.
- Treat symptoms of heart failure while diagnostic workup is in progress.
- Vasodilators. Place patient on an ACE inhibitor. Gradually increase the dose; monitor blood pressure, electrolytes, and renal function. If the patient cannot tolerate ACE inhibition, try an angiotensin receptor blocker, for example, losartan 50 mg every day. Place the patient on aspirin, 325 mg per day (Table 4-8).
- Diuresis. Administer full dose furosemide orally (40 mg every day in the morning). A single IV dose may be given to the patient in the office setting to initiate therapy. Daily oral potassium supplementation is often required; however, care must be taken if ACE inhibitors or spironolactone are also prescribed since hyperkalemia may result if excess potassium supplementation is given in the face of ACE inhibition/spironolactone.
- Beta-blockers. Initiate beta-blockade with small doses. Increase the dose slowly. Increased diuresis may be required when beta-blockade is initiated.
- Digitalis. If the patient remains symptomatic, add 0.125 mg PO of digoxin per day.
- Aldactone. If the patient remains symptomatic, add spironolactone 25 once or twice per day. Follow renal function and electrolytes carefully, particularly if ACE inhibitors and/or potassium supplementation have already been prescribed.
- Diet. Specify no table salt, no highsodium-content foods, and no salt in cooking. Advise weight reduction if obesity is present.
- Activity. Make clear that definite activity reduction is needed, with periodic time for rest. Control work stress and avoid strenuous lifting or other forms of isometric exercise. Suggest that the patient purchase a scale and record daily weights. Inform the physician of any sudden weight gain of 3 lbs or more.
- At return appointment in 2 weeks, check blood pressure, electrolytes, BUN, and creatinine levels and examine the patient for signs of CHF. Obtain an ECG if ischemic left ventricular dysfunction was the cause of CHF. If no symptomatic improvement is found, consider increase of ACE inhibitor and diuretic doses. Monitor renal function and electrolytes following the increase in therapy. Beware of hyperkalemia and renal insufficiency that may result from the combination of ACE inhibitors, potassium supplements, and spironolactone. Slowly increase the dose of beta-blocker over many weeks.
- Medical management of severe heart failure
- Acute heart failure
- Institute investigative efforts to determine precipitating cause.
- Treat symptomatically while diagnostic workup is in progress. Symptomatic treatment must be based on the best available evidence of the precipitating cause of acute heart failure: (i) diuretic, IV furosemide (Table 4-7); (ii) vasodilator therapy (e.g., IV nitroprusside, Table 4-8 for details; administration of IV vasodilators may require admission to the intensive care unit for arterial blood pressure monitoring); and (iii) sympathomimetic amines (dopamine or dobutamine). Consider addition of amrinone if the combination of diuretic, positive inotrope (dobutamine or dopamine), and vasodilator does not achieve the desired result.
- Diet. Nothing by mouth during acute episode.
- Activity. Bed rest with head of bed elevated.
- Acute pulmonary edema. See Chapter 5 on pulmonary edema.
- Chronic severe heart failure. Search for underlying etiology as in mild and moderate CHF protocol. Institute symptomatic treatment with IV furosemide and oral ACE inhibition, beta-blockade, and spironolactone. Monitor renal function and electrolytes frequently. Add oral digoxin 0.125 mg every day if the patient remains symptomatic.
- Diuretics. If the patient remains symptomatic despite therapy with IV furosemide, add a daily dose of a thiazide diuretic to the already prescribed dose of furosemide. Increase furosemide dosage to 80 or more mg once or even twice per day as needed to control symptoms and weight gain. (Table 4-7; monitor electrolyte levels closely.) Add spironolactone 25 mg once or twice a day if not already initiated. Note that monitoring of potassium is essential when this regimen is used concurrently with digitalis.
- Vasodilator therapy. Monitor blood pressure carefully while titrating upward on ACE inhibitor dosage. Unless contraindicated, place patients on one aspirin (325 mg) per day.
- Diet. Restrict sodium as severely as the patient can tolerate. Advise weight reduction as needed in obese patients.
- Activity. Call for significant reduction, with daily rest periods. Suggest a formal exercise program with supervision (e.g., a cardiac rehabilitation program). Suggest that the patient purchase a scale and record daily weights. Inform the physician of any sudden weight gain of 3 lbs or more.
- Refractory heart failure. If heart failure persists despite an intensive search for remediable underlying or precipitating cause and intensive symptomatic therapy, refractory heart failure is said to exist.
- Carefully review treatment to date. Have any possible precipitants been overlooked? Is patient complying with the therapeutic regimen?
- Repeat selected tests, for example, echocardiography and catheterization.
- Hospitalize the patient in an intensive or coronary care unit for IV therapy with nitroprusside alone or in combination with dopamine or dobutamine.
- Consider a trial of amrinone therapy if therapy with vasodilators and IV dobutamine fails.
- If combination therapy is successful, devise an outpatient regimen with maximum tolerated doses of diuretics, spironolactone, beta-blockers, and vasodilators (see Section III.A.4.d.).
- Consider biventricular pacing.
- In carefully selected patients, consider cardiac transplantation.
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Barold SS. What is cardiac resynchronization therapy? Am J Med 2001; 111: 224–232.
Biventricular pacing is effective therapy in patients with CHF.
Braunwald E. Congestive heart failure: a half century perspective. Eur Heart J 2001;22:825–836.
An extensive review of the pathophysiology, clinical manifestation, and therapy of CHF.
Brophy JM, Joseph L, Rouleau JL. Beta-blockers in congestive heart failure: a Bayesian meta-analysis. Ann Intern Med 2001;134:550–560.
Beta-blocker therapy is associated with clinically meaningful reductions in morbidity and mortality in patients with stable CHF.
Caputo R, Laham R. Acute heart failure in the intensive care setting. In: Rippe JM, Irwin RS, Fink MP, et al., eds. Intensive care medicine. Boston: Little, Brown and Company, 1995.
A comprehensive review of acute heart failure and its management in the coronary care unit.
Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 2001;344:873–880.
Atrioventricular pacing improves exercise tolerance in CHF patients with intraventricular conduction delay on the ECG.
Drazner MH, Rame JE, Stevenson LW, et al. Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure. N Engl J Med 2001;345:574–581.
In patients with CHF, both elevated jugular venous pressure and a third heart sound are associated with adverse outcomes.
The effect of digoxin on mortality and morbidity in patients with heart failure: the Digitalis Investigation Group. N Engl J Med 1997;336:525–533.
Digoxin decreases heart failure admissions to hospital but not mortality in patients with CHF.
Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS): the CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429–1435.
This study showed that the addition of an ACE inhibitor to digoxin and diuretic improved 6-month survival in patients with severe heart failure.
Feldman AM, Combes A, Wagner D, et al. The role of tumor necrosis factor in the pathophysiology of heart failure. J Am Coll Cardiol 2000;35:537–544.
A review of the role of tumor necrosis factor and other cytokines in the pathophysiologic sequence of heart failure.
Francis GS. Pathophysiology of chronic heart failure. Am J Med 2001;110(7A):37S–46S.
A concise review of current knowledge of the pathophysiology of CHF.
Gomberg-Maitland M, Baran DA, Fuster V. Treatment of congestive heart failure: guidelines for the primary care physician and the heart failure specialist. Ann Intern Med 2001;161:342–352.
A concise review of modern therapy for patients with CHF.
Krumholz HM, Chen YT, Radford MJ. Aspirin and the treatment of heart failure in the elderly. Ann Intern Med 2001;161: 577–582.
Daily aspirin decreases mortality in older patients with CHF.
Leier CV, Alvarez RJ, Binkley PF. The problem of ventricular dysrhythmias and sudden death mortality in heart failure: the impact of current therapy. Cardiology 2000;93:56–69.
Advances in the management of patients with CHF have decreased sudden death in the heart failure population.
Mosterd A, Cost B, Hoes AW, et al. The prognosis of heart failure in the general population: the Rotterdam Study. Eur Heart J 2001;22:1318–1327.
Heart failure is a disease of older individuals and carries a poor prognosis. Sudden death is markedly increased in this population.
Packer M. Current role of beta adrenergic blockers in the management of chronic heart failure. Am J Med 2001;110(7A): 81S–94S.
A review of the use of beta-blockers in the management of heart failure.
Packer M, Coats AJS, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651–1658.
The beta-blocker carvedilol decreased morbidity and mortality in patients with severe CHF.
Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure: Atlas Study Group. Circulation 1999;100:2312–2318.
Higher doses of lisinopril were better than lower doses in decreasing morbidity in patients with heart failure.
Recommendations for exercise training in chronic heart failure patients. Eur Heart J 2001;22:125–135.
Specially designed exercise training programs benefit patients with chronic CHF.
Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure: task force for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001;22:1527–1560.
Current guidelines for understanding, diagnosing, and treating patients with heart failure.
Rich MW, McSherry F, Williford, WO, et al. Effect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study. J Am Coll Cardiol 2001;38:806–813.
Increasing age is associated with progressively worse outcomes for patients with CHF; however, the benefit of digoxin was maintained despite advancing age.
A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001;344:1659–1667.
The beta-blocker bucindolol decreased morbidity but not mortality in patients with severe heart failure.