Heart Failure

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Chapter 19 Heart Failure

Heart failure is a clinical syndrome that occurs as the end result of any structural or functional cardiac disorder that impairs the ability of the ventricles to fill with or eject blood. In Western countries coronary artery disease and hypertension are its most common causes. In the United States heart failure affects more than 5 million people and results in significant impairment of quality of life, frequent hospitalizations, and poor long-term survival rates (Fig. 19-1).¹ The number of deaths from heart failure is increasing despite advances in diagnosis and treatment. This increase is due in part to an aging population and to improved survival after acute myocardial infarction.²

Figure 19.1 Trends in age-adjusted survival after the onset of heart failure in men (top panel) and women (bottom panel).

(From Levy D, Kenchaiah S, Larson MG, et al: Long-term trends in the incidence of and survival with heart failure. N Engl J Med 347:1397-1402, 2002, with permission. Copyright © 2005 Massachusetts Medical Society.)

ACUTE HEART FAILURE

Acute heart failure encompasses a heterogeneous group of patients, clinical syndromes, and pathophysiologic processes and has no widely accepted system of classification or nomenclature. Acute heart failure includes both de novo heart failure and decompensated chronic heart failure. The emphasis here is on severe acute heart failure that requires admission to the intensive care unit (ICU)—that is, patients with pulmonary edema and cardiogenic shock. Acute heart failure of this severity usually occurs as a consequence of ST-segment-elevation myocardial infarction (STEMI).

Pathophysiology

Impaired left ventricular function leads to increased left ventricular end-diastolic pressure (LVEDP) and reduced stroke volume. Increased LVEDP causes increased pulmonary capillary hydrostatic pressure, which results in the increased filtration of protein-poor fluid into the pulmonary interstitium (Equation 1-12). Moderately increased left atrial pressure (18 to 25 mmHg) results in interstitial edema, which is defined as fluid accumulation in the peribronchovascular spaces; severely increased left atrial pressure (>25 mmHg) results in alveolar edema, which is defined as fluid accumulation in the alveoli.³ Interstitial edema reduces lung compliance and leads to increased work of breathing. Alveolar edema causes increased work of breathing and intrapulmonary shunting, leading to hypoxemia. Acute pulmonary edema can occur in the absence of increased circulating volume or pathologic fluid retention.

Hypotension and low cardiac output lead to activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and to increased secretion of natriuretic peptides and endothelins. Activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system causes tachycardia, arteriolar and venous vasoconstriction, and sodium and water retention by the kidneys. Vasoconstriction is exacerbated by the production of endothelins but is partly ameliorated by the actions of atrial (A-type) and brain (B-type) natriuretic peptides (ANP, BNP) which are secreted by the atria and ventricles, respectively, and cause vasodilatation and natriuresis. Blood flow is directed away from the skin, skeletal muscle, gut, liver, and kidneys and is preferentially directed to the heart and the brain. Myocardial oxygen consumption is increased, which may exacerbate ischemia.

Systemic hypoperfusion leads to lactic acidosis and oliguric renal failure. Severe acidemia aggravates myocardial dysfunction, whereas renal dysfunction exacerbates fluid retention. Over a period of days fluid retention leads to elevated systemic venous pressure and dependent edema, even in the absence of right ventricular dysfunction. Catecholamines and other substances that evolve during cardiogenic shock have important effects on intermediary metabolism (see Chapter 2) that result in hyperglycemia, lipolysis, and increased protein catabolism.

Following myocardial infarction, contractile dysfunction occurs not only within the region of myocyte necrosis but also in the border zone around the infarction and in other parts of the heart. This process is called myocardial stunning. Stunned myocardium may be recruited to contract by inotropic drugs and typically, it recovers its function spontaneously over a period of several days. Stunning is thought to be due to localized (i.e., cardiac) and systemic inflammation.

Systemic inflammation also occurs with heart failure, cardiogenic shock, and cardiac arrest. Patients with severe heart failure have increased levels of inducible nitric oxide synthetase and various inflammatory cytokines, such as tumor necrosis factor-α and interleukins 1 and 6.⁴ The inducible form of nitric oxide synthetase is involved in the regulation of vascular tone in various disease states and, along with tumor necrosis factor-α, it mediates myocardial depression. In patients resuscitated from cardiac arrest, systemic inflammation may produce a hemodynamic state that resembles septic shock, with pathologic vasodilation and capillary leak.⁵ In addition, there is commonly fever, leukocytosis, and elevations in acute-phase reactants.

Based on a simple pump-failure model of cardiogenic shock, patients would be expected to have profoundly depressed ventricular function (i.e., ejection fraction <20%) and elevated systemic vascular resistance. However, many of the patients with cardiogenic shock in the SHOCK trial registry (see later discussion) did not have elevated systemic vascular resistance, and their average ejection fraction was 30%—that is, only moderate to severely depressed.⁶ These findings may be explained as being a severe systemic inflammatory response to myocardial infarction, shock, and cardiac arrest.

Classification and Clinical Presentation

Acute heart failure may be classified on the basis of the presenting clinical syndrome, the hemodynamic profile, and the severity of symptoms. The European Society of Cardiology system recognizes clinical syndromes ⁷: (1) mild acute decompensated heart failure characterized by fluid overload with or without hypoperfusion; (2) hypertensive acute heart failure in which there is hypertension, preserved left ventricular systolic function, and acute pulmonary edema; (3) acute heart failure with pulmonary edema; (4) cardiogenic shock; (5) high output failure; (6) right heart failure. Acute heart failure may also be classified on the basis of hemodynamic profile. Patients are categorized as “warm” or “cold” on the basis of their systemic perfusion and as “wet” or “dry” on the basis of the presence of congestion (either systemic or pulmonary). Class I is warm and dry, Class II is warm and wet, Class III is cold and dry, and Class IV is cold and wet. After myocardial infarction, the Killip classification is widely used for grading heart failure (Table 19-1).⁸

Table 19-1 Killip Classification of Heart Failure Following Myocardial Infarction

Class I	No signs of heart failure
Class II	Crackles, S₃ gallop, elevated jugular venous pressure
Class III	Pulmonary edema
Class IV	Cardiogenic shock

From Killip T 3rd, Kimball JT: Treatment of myocardial infarction in a coronary care unit: a two-year experience with 250 patients. Am J Cardiol 20:457-464, 1967.

Pulmonary Edema

Pulmonary edema may be cardiogenic or noncardiogenic. A pulmonary artery wedge pressure (PAWP) greater than 18 mmHg defines cardiogenic pulmonary edema. Pulmonary edema that occurs following a myocardial infarction is typically due to left ventricular systolic dysfunction. It may or may not be associated with systemic hypoperfusion. In contrast, “flash” pulmonary edema is commonly associated with preserved systolic function,^9,¹⁰ and the trigger for decompensation is often diastolic dysfunction secondary to a hypertensive crisis.⁹ Other causes of cardiogenic pulmonary edema include acute aortic and mitral valve disease, arrhythmias, atrial myxoma, and high-output states, such as anemia and thyrotoxicosis.

Symptoms and signs of pulmonary congestion include dyspnea, cough, orthopnea, paroxysmal nocturnal dyspnea, respiratory distress (tachypnea, use of accessory muscles), central cyanosis, an S3 gallop, and crackles and wheezes on chest auscultation. Jugular venous pressure may or may not be elevated. Patients with alveolar edema typically have marked respiratory distress and hypoxemia and may produce copious frothy sputum. Patients typically hyperventilate, resulting in hypocarbia and respiratory alkalemia. Hypercarbia and respiratory acidemia occur late and indicate imminent cardiorespiratory arrest.

Cardiogenic Shock

Cardiogenic shock is hypotension (systolic blood pressure below 90 mmHg for more than 30 minutes or systolic blood pressure above 90 mmHg with vasoactive support) in association with tissue hypoperfusion or, if a pulmonary artery catheter (PAC) is in situ, a cardiac output of less than 2.2 l/min/m².¹¹

The main cause of cardiogenic shock is left ventricular systolic dysfunction secondary to acute STEMI. Cardiogenic shock occurs in about 4% of patients following STEMI.¹² Risk factors for cardiogenic shock include extensive infarction, anterior infarction, previous myocardial infarction, low ejection fraction, and multivessel coronary artery disease. Shock is more common in myocardial infarctions that occur in the elderly, in diabetics, and in patients who have histories of cerebral or peripheral vascular disease. Only very rarely does cardiogenic shock develop following non-ST-segment elevation myocardial infarction. Most patients who develop cardiogenic shock do so within 24 hours of the myocardial infarction. In the trial known as should we emergently revascularize Occluded Coronaries in cardiogenic shock (the SHOCK trial; see subsequent discussion), 11% of patients had shock at the time of hospital admission and 75% had developed shock by 24 hours.¹¹

Shock that occurs beyond 24 hours should raise the possibility of a mechanical complication of myocardial infarction, such as papillary muscle rupture, ventricular septal rupture, or ventricular free wall rupture. Another cause of shock following myocardial infarction is right ventricular failure. Approximately 25% of patients with inferior myocardial infarction have right ventricular infarction,¹³ and a proportion of these patients develop right ventricular failure. Cardiogenic shock can also occur for reasons unrelated to myocardial infarction, such as pericardial tamponade, fulminant myocarditis, or acute valvular dysfunction.

Clinical signs of tissue hypoperfusion include cool clammy skin, peripheral cyanosis, oliguria, tachycardia, confusion, and drowsiness. Patients with right ventricular failure may have distended neck veins with visible pulsations (V waves; see Figure 8-11) that are indicative of tricuspid regurgitation. Biochemical abnormalities include hyperglycemia, lactic acidosis, increased blood urea nitrogen and creatinine, and elevations in hepatic transaminases.

Cardiac arrest, typically ventricular fibrillation, occurs in about 3% of patients with STEMI ¹² and may be the presenting feature. At least 25% of patients who subsequently develop cardiogenic shock will have had a cardiac arrest, usually at presentation.¹¹ Following cardiac arrest, patients may suffer hypoxic ischemic encephalopathy (HIE; see Chapter 37). Cardiogenic shock is the leading cause of death after acute myocardial infarction and is an important cause of multiple organ dysfunction syndrome (MODS).

Diagnosis

The diagnosis of acute heart failure rests on clinical assessment, electrocardiography, chest radiography, echocardiography, and laboratory tests. Diagnostic assessment should be directed at confirming the diagnosis of heart failure and identifying the cause. The differential diagnoses of pulmonary edema and cardiogenic shock are listed in Table 19-2.

Table 19-2 Differential Diagnosis of Noncardiogenic Pulmonary Edema and Cardiogenic Shock

Pulmonary Edema Without Shock

ARDS

Transfusion-related acute lung injury

Neurogenic pulmonary edema

Cardiogenic Shock

Massive pulmonary embolism

Occult hypovolemic shock

Septic-shock-induced severe myocardial depression

Anaphylaxis

Aortic dissection with tamponade and/or acute aortic regurgitation

Pericardial tamponade (e.g., due to malignant effusion)

Mechanical complication of myocardial infarction:

Acute mitral regurgitation

Ventricular septal rupture

Ventricular free wall rupture

ARDS, acute respiratory distress syndrome.

Clinical Assessment

Symptoms are generally nondiscriminatory. An exception is a history of paroxysmal nocturnal dyspnea, which implies a cardiac cause for shortness of breath. Risk factors for and a previous history of coronary artery disease should be sought. Chest pain may be suggestive of myocardial infarction or point to another diagnosis (see Table 18-4). Systemic conditions that are associated with heart failure, such as collagen vascular diseases, pregnancy, and thyrotoxicosis, may be identified. Features suggestive of acute cardiomyopathy are outlined subsequently.

On physical examination, the finding of an S3 gallop is a specific, but insensitive, sign of heart failure.¹⁴ Both S3 gallop and an elevated jugular venous pressure are independently associated with adverse outcome.¹⁵ Crackles and wheezes are common but nondiscriminatory. A murmur may indicate valvular dysfunction or a mechanical complication of myocardial infarction.

Electrocardiogram and Chest Radiograph

An electrocardiogram (ECG) may show evidence of cardiac disease, such as STEMI, left ventricular hypertrophy, or an arrhythmia, but it cannot be used to confirm the diagnosis of heart failure.

On the chest radiograph, useful information is obtained from the cardiac silhouette and the pulmonary vasculature. With de novo heart failure, cardiac size is not enlarged. Thus, an enlarged cardiac silhouette indicates a chronic process or a pericardial collection. The shape of the cardiac contour may be useful in differentiating a pericardial fluid collection from left or right ventricular dilatation. Features suggestive of a specific valve abnormality, such as mitral stenosis, may be apparent. The chest radiograph may demonstrate interstitial or alveolar edema (see Chapter 6). Features suggestive of a cardiogenic cause may also be apparent (see Table 27-5). Radiographic signs of pulmonary edema may develop very rapidly but their resolution lags behind clinical recovery, often by several days.

Echocardiography

Echocardiography is the single most useful test in the evaluation of patients with heart failure.² Two-dimensional and Doppler imaging allows for the evaluation of global and regional left ventricular systolic function, left ventricular diastolic function, right ventricular function, and valvular function. Uncommon conditions such as constrictive pericarditis, pericardial tamponade, congenital heart disease, and restrictive or obstructive cardiomyopathy may be identified. In most circumstances, transthoracic echocardiography (TTE) is adequate, although transesophageal echocardiography may be required in patients who are mechanically ventilated because image quality is often poor with TTE.¹⁶

Laboratory Tests

The plasma level of BNP is elevated in patients with raised LVEDP and may be used to help determine the cause of acute dyspnea. Heart failure is “very improbable” when the plasma BNP concentration is below 100 pg/ml and “very probable” when it is above 500 pg/ml; when accompanied by a history of heart failure or strong clinical suspicion, heart failure is “very probable” when the BNP concentration is between 100 and 500 pg/ml.¹⁷ However, BNP levels must be interpreted with caution because they also are elevated in a range of other conditions encountered in the ICU, such as aortic stenosis,¹⁸ pulmonary embolus,¹⁹ cardiac surgery sequelae,²⁰ septic shock,²¹^–²³ and acute respiratory distress syndrome.²⁴ BNP levels are commonly elevated above 500 pg/ml in patients who are critically unwell, independent of any cardiac dysfunction.²³ BNP levels are also increased in renal failure, and a cutoff value of 200 pg/ml to exclude heart failure is recommended when the glomerular filtration rate is less than 60 ml/min.¹⁷ Conversely, BNP levels may be normal at the time of admission in patients with flash pulmonary edema.

As an alternative to BNP, the plasma concentration of N-BNP, the N-terminus of pro-BNP, may be used, in which case the recommended lower cutoff value to exclude heart failure is 125 pg/ml in patients younger than 75 years of age and 450 pg/ml in patients older than 75 years.¹⁷ An elevated troponin level supports a diagnosis of myocardial infarction but, as with BNP, elevated troponin levels can occur in a range of conditions (see Table 18-7) other than acute coronary syndromes.

Features Suggestive of Acute Cardiomyopathy

Severe acute heart failure is occasionally caused by cardiomyopathy. The diagnosis is suggested by the abrupt onset of severe biventricular failure in a young patient in association with ventricular arrhythmias and widespread repolarization (ST segment) abnormalities on the ECG. A history of recent viral illness or drug ingestion (e.g., alcohol, cocaine, antiretroviral drugs, doxorubicin) suggests the diagnosis. The main differential diagnosis is myocardial ischemia and infarction. Biventricular involvement and a normal coronary angiogram are strongly suggestive of acute cardiomyopathy. The diagnosis may be confirmed by right ventricular endomyocardial biopsy.

Management of Acute Heart Failure

The management of acute severe heart failure involves:

(1) supportive care of the heart, lungs, and other organs;

(2) treating the cause of the heart failure.

Immediate Resuscitation

Patients may be critically unwell, with respiratory distress, hypoxemia, impaired mentation, hypotension, and severe metabolic disturbance. Treatment and diagnosis must occur simultaneously. Initial management consists of the administration of high-flow oxygen through a face mask, insertion of an intravenous cannula, and application of standard monitors (ECG, pulse oximeter, and blood pressure cuff). Blood samples should be obtained for arterial blood gases, blood chemistry, glucose, BNP, renal and hepatic function, troponin, and complete blood count. A chest radiograph and an echocardiogram should be obtained as soon as practical. An intraarterial catheter and a urinary catheter should be inserted in patients who are acutely unwell.

Patients with severe respiratory failure, reduced levels of consciousness, or severe hypotension (systolic blood pressure below 60 mmHg) should be intubated and ventilated. With acute myocardial infarction, urgent coronary angiography is indicated and takes precedence over all but immediately life-preserving resuscitation.

Treatment of Acute Pulmonary Edema

Pharmacotherapy

Pharmacotherapy ²⁵ for acute pulmonary edema consists of diuretics, morphine, and vasodilators. Intravenous furosemide is the most commonly used initial therapy for acute heart failure,²⁶ and it provides relief from pulmonary congestion. Furosemide must be used with caution because it can cause hypokalemia, hypomagnesemia, hypovolemia, and renal dysfunction. Morphine reduces the sensation of dyspnea and acts as a weak vasodilator, thereby reducing preload and afterload. Morphine must be used cautiously in patients with low cardiac output or reduced level of consciousness. Small intravenous boluses (1 to 3 mg) should be titrated to effect.

Venodilatation decreases systemic venous return and therefore reduces left ventricular preload, whereas arteriolar dilatation reduces left ventricular afterload. Both effects reduce left atrial pressure. Intravenous nitroglycerin dilates both veins and arterioles and is useful for treating cardiogenic pulmonary edema. Higher doses (>1 μg/kg/min) than are required to treat angina may be needed. Nitroprusside, a potent arteriolar dilator, is also effective in reducing left atrial pressure but can cause marked hypotension, even at low doses. It is particularly useful in patients with acute pulmonary edema secondary to hypertensive crisis. It should be administered only to patients with invasive blood pressure monitoring. Nesiritide, an analogue of BNP, is a mixed vein and arteriole vasodilator that has a mild diuretic effect.²⁷ In patients with acute heart failure, nesiritide is more effective than nitroglycerin in improving symptoms and reducing left atrial pressure.^28,²⁹ Vasodilators should be avoided in patients with cardiogenic shock.

Ventilatory Support

Patients with persistent hypoxemia (S_aO₂ <90%) or marked respiratory distress despite high-flow face-mask oxygen should be given continuous positive airways pressure (CPAP), which is administered by using a tight-fitting face mask. CPAP increases functional residual capacity, reduces work of breathing, improves oxygenation, and reduces left ventricular afterload. Initial CPAP settings of 10 cm H₂O with 100% oxygen are appropriate. The inspired oxygen concentration should be titrated to achieve an S_aO₂ above 90% with a stable arterial carbon dioxide tension and pH. Patients should be closely monitored for deteriorating hemodynamics, worsening gas exchange, and exhaustion. Criteria for endotracheal intubation are outlined in Table 27-3.

If endotracheal intubation is required, it may be fraught with problems for two reasons. First, copious quantities of frothy edema fluid may fill the pharynx, making laryngoscopy extremely difficult. If this occurs, an assistant can place the tip of a suction catheter directly into the laryngeal inlet during laryngoscopy to allow visualization of the vocal cords. Second, the loss of sympathetic tone associated with general anesthesia may precipitate severe hypotension. Vasopressors should be drawn up in preparation for this state. Invasive ventilation for patients with acute pulmonary edema is described in Chapter 29.

Treatment of Hypoperfusion and Shock

Monitoring and Investigations

In addition to the monitors listed earlier, a central venous catheter should be placed in patients with cardiogenic shock to measure central venous pressure and superior vena caval oxygen saturation (S_SVCO₂; see Chapter 20) and to administer vasoactive drugs. Note, however, that central venous pressure may be a very misleading measure of preload in patients with acute heart failure (see Chapter 8). A PAC is not indicated routinely but should be considered in patients who do not respond in predictable ways to standard treatment.⁷ In the absence of a central venous catheter, inodilator therapy (e.g., dobutamine, milrinone) may be administered via a peripheral intravenous cannula.

Arterial blood gases, lactate, glucose, electrolytes, S_VO₂, (or S_SVCO₂) should be measured every few hours during the acute period of illness. Urine output should be measured hourly. Initially, troponin measurement and a 12-lead ECG should be repeated every 6 hours. Other laboratory tests and chest radiography may be repeated daily. The initial echocardiogram should be repeated if there is a major change in the patient’s clinical state (e.g., recurrence of pulmonary edema) and again following recovery from acute illness.

Support of Other Organ Systems

Brain

Patients who suffer an out-of-hospital cardiac arrest should undergo therapeutic cooling to 32° to 34°C for 12 to 24 hours followed by passive rewarming to 36°C to protect against HIE.³⁵ There may also be a role for therapeutic hypothermia in patients who suffer a prolonged in-hospital cardiac arrest. This is discussed in greater detail in Chapter 37.

Because the severity of HIE cannot be predicted with any certainty at the time of presentation, patients should receive aggressive cardiac support until the neurologic status becomes apparent.

Kidneys

Acute renal failure is to be expected with cardiogenic shock, and it can exacerbate pulmonary and systemic congestion, metabolic acidemia, and hyperkalemia. Oliguria and azotemia are normal responses to hypoperfusion and shock (see Chapter 1) and are not in themselves an indication for diuretic or renal replacement therapy. Diuretics may be used initially in patients with pulmonary congestion but if they are ineffective, early institution of renal replacement therapy, usually with continuous hemofiltration, is appropriate.

Gut, Pancreas, and Liver

The intense sympathetic stimulation that accompanies cardiogenic shock leads to marked vasoconstriction within the splanchnic circulation, with the potential for ischemic damage. Hepatic ischemia is manifested as elevations in hepatic transaminases (aspartate and alanine aminotransferase) and is most marked when systemic venous pressure is also increased—that is, with right ventricular dysfunction. Changes in hepatic transaminases take up to 24 hours to reach their maximum values and persist for several days after resolution of shock. With hepatic ischemia there is reduced metabolism of lactate to bicarbonate by the liver, which contributes to metabolic acidemia due to shock. Severe hepatic ischemia may also cause coagulopathy and encephalopathy. Pancreatic amylase may also be increased.

Gut dysfunction is usually manifested as impaired tolerance of enteral nutrition and ileus, but occasionally, mesenteric infarction occurs. The role of early feeding in patients with cardiogenic shock has not been specifically investigated. However, after 24 hours it is reasonable to commence enteral nutrition via a nasogastric tube at a low volume (e.g., 10 to 20 ml/hr) and slowly increase it to the goal rate. If enteral nutrition has not been fully established within 2 to 4 days, postpyloric feeding via a nasojejunal tube should be commenced.

Adjuvant Treatments

Anticoagulation

Myocardial infarction may be treated with antiplatelet, antithrombotic, and thrombolytic drugs. In patients not already receiving heparin, low molecular weight heparin should be considered as prophylaxis against deep venous thrombosis.

Glucose Control

As described earlier, hyperglycemia is common in patients with acute heart failure. In medical patients who require prolonged ICU stay, there is some evidence of improved outcome—but some increase in morbidity—with tight glucose control.^36,³⁷ As a minimum, hyperglycemia (glucose <180 mg/dl or 10 mmol/l) should be avoided. This may require high doses of insulin because shock is associated with marked insulin resistance.

Corticosteroids

Patients resuscitated from cardiac arrest have an inadequate stress release of cortisol.³⁸ Furthermore, a subgroup of patients with shock due to sepsis benefit from corticosteroid administration (see Chapter 36).³⁹ Although there is no direct evidence of improved outcome from cardiogenic shock, in patients who are critically unwell and are receiving high-dose inotropic support, the administration of corticosteroids in a replacement dose (e.g., hydrocortisone 50 mg 6 hourly) may be beneficial.

Acid Prophylaxis

Routine prophylaxis against gastrointestinal hemorrhage by a proton pump inhibitor (e.g., pantoprazole 40 mg intravenously daily) is indicated in all patients with cardiogenic shock, particularly if they are receiving antiplatelet or antithrombotic medications.

Statins

In addition to their role in the treatment of dyslipidemia, statins have antiinflammatory effects, and their use has been linked to improved outcome after acute myocardial infarction ⁴⁰ and septic shock.⁴¹ In the absence of hepatic ischemia, it is reasonable to administer a statin to all patients with postmyocardial infarction cardiogenic shock.

Treating the Causes

Myocardial Infarction

Patients with cardiogenic shock secondary to STEMI should receive urgent catheter-based or surgical revascularization.^7,⁴² This recommendation is based primarily on the results of the SHOCK trial¹¹ and subsequent follow-up studies.⁴³ In the SHOCK trial, patients with cardiogenic shock were randomized to medical treatment, including thrombolysis and IABP, or coronary revascularization, either by percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). The 6-month¹¹ and 1-year⁴³ survival rates were better in patients treated with PCI or CABG. The benefits of revascularization extended to 12 to 18 hours after the onset of shock, even if shock presented up to 36 hours following myocardial infarction. Although no survival benefit was observed in patients over 75 years of age, that finding may have been the result of a higher baseline risk and a small sample size in this group. Thus, urgent PCI or CABG may still be indicated in selected patients over 75.⁴⁴ The choice between PCI and CABG depends on the findings at angiography (see Table 9-1). Patients with respiratory distress or hemodynamic instability should be intubated and ventilated prior to angiography. If not already in situ, a central venous catheter and IABP may be inserted in the angiography suite at the completion of the procedure.

Patients who present within 12 hours of a myocardial infarction to a hospital without facilities for urgent coronary angiography should undergo thrombolysis (see Chapter 18). Despite this recommendation, there is scant evidence that thrombolysis improves outcomes after cardiogenic shock. For patients who suffer a mechanical complication of myocardial infarction, urgent surgical repair may be lifesaving. However, even with appropriate treatment, mortality rates are very high (see Chapter 9).

Valvular Dysfunction

Patients with acute valvular dysfunction—for instance, dysfunction secondary to infective endocarditis or rupture of mitral chordae—should undergo urgent surgical repair.

Acute Myocarditis

Patients with myocarditis have been treated with a range of immunosuppressant regimens. Therapies that have been used include high-dose methylprednisolone, azathioprine, cyclosporine, intravenous immunoglobulin, and plasmapheresis. To date, none of these therapies has been shown to improve survival rates.^45,⁴⁶

Weaning Acute Support

After a period of stability, patients should be weaned from cardiac and respiratory support. First, inotropic support should be gradually reduced to a low level (e.g., epinephrine 0.1 μg/kg/min or the equivalent), and then the IABP should be removed. In cases of isolated pulmonary edema, usually only a short period of ventilatory support is required—often less than 24 hours. In cardiogenic shock, ventilatory support may be required for several days, in which case a tracheotomy should be considered. Low-dose inodilator therapy should be continued during the period of ventilatory weaning. If pulmonary edema develops during weaning, a repeat echocardiogram should be performed. Rapid and contemporaneous discontinuation of IABP, mechanical ventilation, and inodilator therapy—all of which reduce left ventricular afterload—can precipitate acute pulmonary edema, low cardiac output, and hypotension.

Once renal function has stabilized, an angiotensin-converting enzyme (ACE) inhibitor may be substituted for the intravenous inodilator. This may occur during the late phase of ventilatory weaning. The ACE inhibitor should be started at a low dose (e.g., enalapril 2.5 mg daily) and slowly increased over several days. Patients must be carefully monitored for hypotension, hyperkalemia, and renal dysfunction. β Blockers have no place in the early recovery phase after acute severe heart failure. Regular treatment with a loop diuretic should be commenced once renal replacement therapy is no longer required, with the dose tapered to a low dose once the patient has returned to his or her “dry” weight.

Myocardial stunning and systemic inflammation usually have resolved after a week. If at this time echocardiography demonstrates severely impaired ventricular function and the patient’s clinical condition remains very poor—that is, the patient is inotrope- and ventilator-dependent, is intolerant of weaning, and has MODS—it may be helpful to perform a limited bedside dobutamine stress echocardiogram to assess myocardial viability. The absence of viability suggests that further improvement in cardiac function will be limited or nonexistent. This information can then be used to guide further management: either referral for transplantation or a VAD or compassionate end-of-life care.

Outcome

Acute heart failure carries a poor prognosis. In one large series, 13.5% of patients hospitalized with acute heart failure died between admission and 12-week follow-up.⁴⁷ The presence of hypotension (systolic blood pressure <115 mmHg) and elevated blood urea nitrogen (>43 mg/dl or 15.3 mmol/l) and creatinine (>2.75 mg/dl or 243 μmol/l) are predictors of death.⁴⁸ Patients with all three risk factors on admission have an in-hospital mortality rate of about 20%.⁴⁸ The mortality rate after severe cardiogenic shock associated with myocardial infarction is about 50%.¹¹ The mode of death is unsupportable cardiac failure, MODS, or HIE. However, of survivors, many make a good recovery and are in New York Heart Association (NYHA) functional class I or II.⁶

CHRONIC HEART FAILURE

Patients with chronic heart failure are admitted to the ICU for the management of acute decompensation (the causes are listed in Table 19-3) and for various cardiac operations, such as CABG surgery, ventricular remodeling surgery, mitral valve surgery, insertion of a mechanical device, and heart transplantation. Heart failure is a complicating factor in about 30% of general ICU admissions.⁴⁹

Table 19-3 Causes of Acute Exacerbations of Chronic Heart Failure

Progression of chronic heart failure

Acute coronary syndrome

Accelerated hypertension or poorly controlled hypertension

Acute valve dysfunction or chronic progression of existing severe valve lesion

Arrhythmia

Infections, particularly pneumonia or septicemia

Major surgery

Renal dysfunction

Severe brain injury

Exacerbation of COPD

Aortic dissection

Drugs (e.g., nonsteroidal antiinflammatory drugs, alcohol)

Poor compliance with medical therapy

Excess fluid or salt intake

High output syndromes (e.g., anemia, thyrotoxicosis, shunts)

COPD, chronic obstructive pulmonary disease.

Modified from Nieminen MS, Bohm M, Cowie MR, et al: Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J 26:384-416, 2005.

Pathophysiology

The neurohumoral processes described for acute heart failure are applicable to chronic heart failure. Neurohumoral activation, along with abnormal myocyte stretch, leads to ventricular remodeling, which is the hallmark pathophysiologic feature of chronic heart failure. Remodeling involves myocyte hypertrophy, myocyte slippage, and interstitial fibrosis. The left ventricle dilates and loses its cylindrical shape, adopting a more spherical conformation. This change in shape reduces pumping efficiency, increases wall stress, leads to functional mitral regurgitation, and impairs right ventricular function.

Ventricular remodeling occurs with a variety of cardiac pathologies, including chronic pressure overload, chronic volume overload, and after myocardial infarction. Severe pressure overload leads primarily to concentric ventricular hypertrophy and diastolic dysfunction, whereas severe volume overload leads to eccentric hypertrophy and systolic dysfunction. Remodeling that occurs following myocardial infarction is a global phenomenon that results in ventricular dilatation and a generalized reduction in contractility. If appropriate treatment is introduced early enough, remodeling may be ameliorated or reversed.

A further cause of left ventricular systolic and diastolic dysfunction in patients with coronary artery disease is hibernating myocardium, which is a state of chronic ischemic dysfunction. Contractile dysfunction secondary to hibernating myocardium may recover following revascularization.

Classification and Clinical Presentation

Chronic heart failure may be classified on the basis of cause, structural abnormality, clinical syndrome, symptom severity, and disease progression. With respect to cause, the majority of heart failure is due to coronary artery disease, hypertension, valvular dysfunction, and cardiomyopathy. Structurally, heart failure may be classified as left ventricular, right ventricular, or biventricular. Left ventricular dysfunction may be systolic or diastolic. Clinically, patients with heart failure present with: (1) a syndrome of reduced exercise tolerance; (2) a syndrome of fluid retention; (3) no symptoms or symptoms relating to another condition (e.g., myocardial infarction or stroke).² Systemic congestion can be difficult to diagnose clinically in patients with chronic heart failure: in one study, physical findings of congestion were detected in only half the patients found to be hypervolemic by using iodine ¹³¹-tagged albumin.⁵⁰ Anemia is a useful marker of chronic volume overload.

The severity of symptoms may be categorized according to the NYHA functional classification (Table 19-4). This classification is widely used and is helpful prognostically, but it has a number of limitations. First, the severity of symptoms does not always correlate with the severity of the underlying cardiac dysfunction. Second, even though chronic heart failure is a progressive condition, symptoms do not usually follow an inexorable pattern of decline but fluctuate, even in the absence of obvious precipitating factors or changes in medication. Thus, it is common for patients to be assigned to more than one NYHA class or to be reassigned from one class to another. NYHA functional class does not determine an evidenced-based approach to therapy.

Table 19-4 New York Heart Association Functional Classification

Class I	Symptoms on levels of exertion that limit normal individuals
Class II	Symptoms on ordinary exertion
Class III	Symptoms at less than ordinary exertion
Class IV	Symptoms at rest

The American College of Cardiology and American Heart Association have classified chronic heart failure as a progressive disorder based on the underlying cardiac disease (see Table 19-5).² This classification system takes into account risk factors for heart failure and the presence of structural heart disease and provides a rational basis for medical intervention.

Table 19-5 Stages in the Development of Heart Failure and Therapeutic Recommendations by Stage

Diastolic Heart Failure

Heart failure is often thought of as being synonymous with impaired left ventricular systolic function and is graded by the severity of the reduction in ejection fraction. However, between 20% and 60% of patients with signs and symptoms of heart failure have normal or near-normal ejection fraction.² The primary abnormality in many of these patients is thought to be reduced ventricular compliance (i.e., diastolic dysfunction) resulting in increased diastolic ventricular pressure. In many cases there is pathologic fluid retention. This syndrome occurs more commonly in the elderly, in women, and in patients with hypertension.⁵¹^–⁵³ Patients typically present with exercise-related dyspnea and may experience episodes of acute decompensation that manifests as flash pulmonary edema. Diagnosis is based on the finding of normal or near-normal ejection fraction and the absence of valvular pathology in a patient with symptoms and signs of pulmonary congestion. There may be echocardiographic evidence of raised left atrial pressure and abnormal diastolic function, either prolonged relaxation or reduced left ventricular compliance (see Chapter 7). Underlying coronary artery disease is very common,¹⁰ and patients may subsequently develop impaired systolic function.

Treatment of Chronic Heart Failure

Treatment of chronic heart failure is directed primarily at limiting or reversing ventricular remodeling. Thus, appropriate treatment depends on the underlying cause of the heart failure. For hypertensive heart disease, treatment involves effective control of blood pressure as evidenced by resolution of left ventricular hypertrophy. For severe valvular heart disease, valve repair or replacement may be indicated. In the case of heart failure secondary to myocardial infarction, pharmacotherapy is directed at antagonizing the effects of neurohumoral activation. In certain situations, surgical or device-based treatment is indicated.

Medical Treatment of Chronic Heart Failure

The evidenced-based treatment of chronic heart failure is summarized in Tables 19-5 and 19-6.²

Table 19-6 Evidence-Based Medical Therapy for Chronic Heart Failure

Diuretics

Diuretics remain an important component of therapy for chronic heart failure. However, diuretic use has been linked with an increased incidence of fatal arrhythmias in patients with reduced ejection fraction ⁵⁴ and has been associated with increased mortality rates in patients with acute heart failure.⁵⁵ Thus, diuretics should not be used as monotherapy, and the dosage should be titrated to the minimum level required to control the symptoms of congestion.

Inhibition of the Renin-Angiotensin-Aldosterone System

ACE Inhibitors and Angiotensin Receptor Blockers.

In patients with chronic heart failure, treatment with ACE inhibitors leads to improvement in symptoms, increased exercise capacity, inhibition of ventricular remodeling, and decreased mortality rates.^56,⁵⁷ ACE inhibitors are indicated for all stages of heart failure, from patients with asymptomatic left ventricular dysfunction to those with severe NYHA class IV symptoms. The effects of ACE inhibitors are a class effect, and no specific agent is recommended. Generally, higher dosages should be aimed for (see Table 3-4). The combination of an ACE inhibitor and an angiotensin-receptor blocker (ARB) results in a lower incidence of death and hospital admission but in a higher risk for developing hypotension and renal impairment than is found when patients are treated with an ACE inhibitor alone.⁵⁸ ARBs may also be used as an alternative to ACE inhibitors in patients who are intolerant of ACE inhibitors⁵⁹ and for treating heart failure with preserved left ventricular systolic function (see subsequent material).

Aldosterone Antagonists: Spironolactone and Eplerenone.

Aldosterone levels remain elevated in patients with heart failure despite ACE inhibitor therapy, and those levels contribute to the progression of the disease process. Treatment with spironolactone improves survival rates in patients with chronic heart failure,⁶⁰ whereas treatment with eplerenone improves survival rates in patients with left ventricular dysfunction following myocardial infarction.⁶¹

The aim when using aldosterone antagonists is to alter the natural history of the heart failure rather than to provide short-term benefit in terms of diuresis. Low-dose spironolactone (e.g., 25 mg/day) is indicated in addition to ACE inhibitor and loop diuretic therapy in patients with severe heart failure secondary to left ventricular systolic dysfunction. Contraindications and precautions are listed in Chapter 3.

Inhibition of the Sympathetic Nervous System

Traditionally, β blockers were contraindicated in patients with heart failure, and this remains true in acute heart failure, when activation of the sympathetic nervous system is needed to maintain blood flow to essential organs. However, in chronic heart failure, activation of the sympathetic nervous system continues despite ACE inhibitor and diuretic therapy and contributes to the disease’s progression. Antagonism of the sympathetic nervous system with β blockers leads to a reduction in hospitalizations and improved survival rates in patients with chronic heart failure.⁶²^–⁶⁴ However, β blockers do not improve—and may worsen—symptoms in the short term.

β Blockers should be started in patients who have been established on ACE inhibitors and loop diuretics and who are relatively stable and without overt clinical congestion. Carvedilol can be initiated early after an episode of decompensated heart failure (e.g., prior to hospital discharge) but patients should still be at or close to their dry weight and should not have recently required therapy with an inotrope. The starting dosage should be low (3.125 mg/day) and should be increased every 2 weeks.

Risks of Combined Neurohumoral Antagonists

Patients with heart failure associated with low left ventricular ejection fraction should be considered for treatment with a loop diuretic, an ACE inhibitor, a β blocker, spironolactone, and an ARB. All these agents may lower blood pressure, and although some patients may tolerate full doses of all these medications, others may not, particularly those with low blood pressure and those with significant renal dysfunction. Therapy should be individualized.

With the clear benefits of the therapies outlined, the use of digoxin has decreased. Its use should be restricted to patients with coexisting atrial fibrillation and to those with severe heart failure that is resistant to all other therapies.

Titration of Heart Failure Treatment

Titration of pharmacotherapy for chronic heart failure is based primarily on the clinical assessment of signs and symptoms and on functional capacity. Recently, BNP levels have been proposed as a method of guiding therapy, and in one small study this approach resulted in a reduction in adverse cardiovascular events.⁶⁵ However, targeting a specific BNP level in an individual is problematic because some patients maintain high BNP levels despite optimal therapy and minimal symptoms, whereas others have BNP levels within the normal range despite advanced heart failure.^2,¹⁷ Measurement of ejection fraction is useful following a major change in a patient’s clinical status, but it is not indicated as routine.²

Treatment of Diastolic Heart Failure

The evidence-based recommendations for the treatment of chronic heart failure pertain largely to patients with impaired left ventricular systolic function. Therapy for heart failure with preserved ejection fraction is largely empiric and involves treatment of hypertension, rate control of atrial fibrillation, diuretics for congestion, and revascularization for coronary artery disease. Recently, treatment with the ARB candesartan has been shown to reduce hospital admissions for worsening heart failure in patients with preserved left ventricular ejection fraction.⁶⁶

Ejection fraction is a relatively crude measure of left ventricular systolic function, and it is likely that many patients with so-called diastolic heart failure actually have impaired systolic function. Thus, other agents, including ACE inhibitors and β blockers, are often used, albeit empirically, in these patients.

Surgical and Device Therapy for Chronic Heart Failure

Despite appropriate pharmacotherapy, the prognosis for patients with heart failure remains poor (see Figure 19-1). For certain patients, surgical or device-based therapy is an alternative.

Heart Failure Surgery

As outlined in Chapter 9, patients with depressed left ventricular function secondary to hibernating myocardium—as identified by a viability study—benefit from myocardial revascularization. Many such patients have extensive three-vessel coronary artery disease, and CABG surgery, rather than PCI, is the preferred method of revascularization. For patients with severe ventricular dilatation (end-diastolic volume index >60 ml/m²) and an anteroseptal scar, surgery to remodel the left ventricle should be considered at the time of CABG surgery (see Chapter 9). If appropriate, mitral valve surgery for mitral regurgitation or resection of endocardium and cryotherapy for arrhythmias may also be performed at that time.

Cardiac Resynchronization

Approximately one third of patients with cardiomyopathy have intraventricular conduction delay, such as left or right bundle branch block.⁶⁷ Abnormal intraventricular conduction with or without delayed atrioventricular conduction is associated with a lack of functional synergy between the left and right ventricles. Echocardiographic findings include paradoxic ventricular septal motion, presystolic mitral regurgitation, and shortened diastolic filling time.⁶⁷ Biventricular pacing improves ventricular function in patients with advanced heart failure and intraventricular conduction delay. Pacing wires are inserted into the right atrium and right ventricle and—via the coronary sinus and cardiac vein—the lateral left ventricular wall. The pacemaker is programmed to provide the appropriate atrioventricular delay and coordinated contraction between the right and left ventricles; hence the term cardiac resynchronization. In appropriate patients, biventricular pacing reverses ventricular remodeling, improves symptoms, and enhances survival rates.^68,⁶⁹ Patients should be considered for biventricular pacing if they fulfill the following criteria: (1) left ventricular ejection fraction less than or equal to 35%; (2) NYHA class III or IV symptoms despite optimal medical therapy; (3) sinus rhythm; (4) QRS duration of greater than 0.12 sec.²