Chapter 22. Ventricular Dysfunction in Critical Illness

• Understanding cardiovascular dysfunction in a critically ill patient requires consideration of cardiac function and systemic vascular factors controlling venous return.
• Compression by surrounding structures (cardiac tamponade) and increased afterload must be considered as external causes or contributors to cardiac dysfunction.
• Decreased ventricular pump function may be due to decreased systolic contractility, increased diastolic stiffness, abnormal heart rate and rhythm, or valvular dysfunction.
• Management of ventricular dysfunction aims to reverse the cause by optimizing preload and afterload and correcting abnormalities in heart rhythm, valve function, and contractility.
• Acute reversible contributions to depressed contractility result from ischemia, hypoxemia, acidosis, ionized hypocalcemia and other electrolyte abnormalities, myocardial depressant factors, and hypo- and hyperthermia.
• Management of acute-on-chronic heart failure progressively includes oxygen; optimizing preload with diuretics, morphine, and nitrates or fluid infusion for hypovolemia; afterload reduction; increasing contractility using catecholamines or phosphodiesterase inhibitors; antiarrhythmic drugs and resynchronization using biventricular pacing; intraaortic balloon counterpulsation; and cardiac transplantation.

This chapter reviews the etiology and management of circulatory disturbances arising in critically ill patients whose primary cause for ventricular dysfunction is more related to complications of other multisystem organ failures without diminishing the possibility that occult ischemic heart disease (see Chap. 25) might be unmasked by the stress imposed by multisystem organ failure or its diverse treatments. I emphasize how critical illness disturbs ventricular function and the systemic factors governing venous return and refer the reader to Chap. 25 for the detailed diagnosis and management of ischemic heart disease. To avoid redundancy, I refer liberally to other chapters in this book that discuss mechanisms for ventricular dysfunction in the context of other diseases (see Chaps. 20, 21, 26, 28, and 29).

Cardiac pump function can be defined by the relation of the heart's output to its input.1 Cardiac output is the most important output of the entire heart, and right atrial pressure (Pra) is an easily measured input of the entire heart. Cardiac output is initially assessed as high, adequate, or inadequate by cardiovascular examination and by clinical evaluation of perfusion. Later, after placement of a central venous catheter to allow measurement of central venous pressure (CVP) and central venous oxygen saturation, after placement of a pulmonary artery catheter, or after echocardiography, cardiac output can be more accurately quantitated. Pra is initially evaluated by clinical examination of distention of the jugular veins and later may be more accurately measured as the CVP. Other outputs, such as stroke work, and other inputs, such as pulmonary artery occlusion (or wedge) pressure (Ppw), serve to quantitate cardiac dysfunction and to determine the specific cause of cardiac dysfunction.

Depressed cardiac function may be due to left ventricular dysfunction, right ventricular dysfunction, external compression (cardiac tamponade), or excessively elevated right or left ventricular afterload. I focus on left ventricular and right ventricular dysfunction because cardiac tamponade is discussed in Chap. 28 and pulmonary embolism in Chap. 27. Yet in every case one should consider whether the pericardium and other structures surrounding the heart or right- and left-side afterloads are affecting cardiac function. The specific causes of ventricular dysfunction, right and left, are decreased contractility (a shift down and to the right of the end-systolic pressure-volume relation), increased diastolic stiffness (a shift up and to the left of the diastolic pressure-volume relation), a change in heart rhythm and rate, and abnormal valvular function. How can one determine the presence of depressed ventricular pump function, distinguish between right and left ventricular dysfunction, and then identify the specific cause?

The Clinical Examination

Left ventricular dysfunction is characterized by high left ventricular filling pressures in relation to cardiac output. Likewise, right ventricular dysfunction is characterized by high right ventricular filling pressures in relation to cardiac output. Importantly, there is a close interaction between the left and right ventricles so that, most commonly, left and right ventricular dysfunction coexist. Initially, clinical examination attempts to identify the presence and severity of depressed cardiac pump function and to distinguish the contributions of right and left ventricular dysfunction. Evaluation of perfusion and mean blood pressure, pulse pressure, and heart rate provide a clinical estimate of whether or not cardiac output is decreased (see Table 21-1). Right ventricular filling pressure may be judged by distention of jugular veins. Evidence of dependent pulmonary crackles on physical examination due to heart failure suggests that left ventricular filling pressure is elevated, usually above 20 to 25 mm Hg. However, in chronic congestive heart failure, where pulmonary lymphatic drainage increases, crackles may not be present even at filling pressures as high as 30 mm Hg. Interstitial edema clearance lags decreases in left atrial pressure (Pla) by hours, so rapid decreases in Pla are not accurately reflected by pulmonary auscultation. An audible third heart sound suggests an elevated Pla in the presence of a dilated left ventricle.2

Central Venous and Right Heart Catheters

In severe ventricular dysfunction or in critical illness, where even mild ventricular dysfunction contributes significantly to severity of illness, more accurate measures of ventricular function than can be determined by clinical examination are required to test and titrate therapy. Important tools in the intensive care unit (ICU) are central venous catheterization, pulmonary artery catheterization, and echocardiographic evaluation (see Chap. 13). Central venous catheterization allows measurement of right ventricular filling pressure (CVP) and central venous oxygen saturation, which can be used to estimate cardiac output by using the Fick equation. Pulmonary artery catheterization, using a thermistor-tipped catheter with a distal port at the tip and a proximal port 30 cm from the tip, can accurately determine cardiac output by using the thermodilution technique. Right ventricular filling pressure (CVP) can be measured with the proximal port. Left ventricular filling pressure may be estimated as the Ppw (with important limitations discussed in Chap. 13). Therefore, the separate contributions of right ventricular and left ventricular dysfunction can be distinguished. Right ventricular afterload can be measured as pulmonary artery pressure (Ppa) by using the distal port of the pulmonary artery catheter, and left ventricular afterload is reflected by measuring systemic arterial pressure. Uncritical use of a pulmonary artery catheter may be associated with no benefit or even an increased mortality rate.3,4 Nonetheless, thoughtful use of a pulmonary artery catheter in the most severely ill may decrease mortality rate.5

Integrating Hemodynamics with Imaging Studies

The distinction between decreased contractility and increased diastolic stiffness cannot be determined by right heart catheterization alone. Accordingly, techniques that image ventricular diastolic and systolic volumes contribute substantially to the information obtained from pulmonary artery catheterization. The presence of enlarged v waves on the Pra trace or on the Ppw trace indicates tricuspid and mitral regurgitation, respectively. However, the size of the v waves depends on a number of factors, including compliance of the atria and ventricles so that accurate assessment of valvular dysfunction using a pulmonary artery catheter alone is impossible. Thus, additional imaging techniques are required to assess valvular function.

The most readily available and useful imaging technique is echocardiography, which can be used to evaluate ventricular function and valvular function (see Chap. 29). An estimated ejection fraction smaller than 0.4 is generally an excellent indicator of decreased contractility in hemodynamically stable patients. However, ejection fraction and related fractional shortening measurements are sensitive to changes in preload and afterload.6,7 In the hemodynamically unstable patient, ejection fraction must be interpreted in conjunction with hemodynamic measurements from systemic and pulmonary artery catheters. Alternatively, echocardiography can be used to estimate ventricular diastolic and systolic volumes and filling of surrounding venous structures. Two distinctions are evident: a small end-diastolic volume (EDV) when filling pressures are normal or high indicates that increased diastolic stiffness contributes to decreased ventricular pump function,8 and a large end-systolic volume (ESV) when afterload is normal or low indicates that depressed contractility contributes to decreased ventricular pump function. Therefore, end-diastolic and end-systolic diameters should be determined separately and interpreted in the light of measured pressures and flows.

Doppler echocardiographic examination allows measurement of the pressure gradient across valves, which is proportional to four times velocity squared, because blood flow across valves is turbulent. For example, it is usually possible to estimate Ppa from the tricuspid regurgitation velocity and CVP. Valvular insufficiency is also identified using Doppler and color Doppler echocardiographic imaging of blood velocities. The major limitation of conventional transthoracic echocardiographic examinations is that critically ill patients frequently are on positive-pressure mechanical ventilation and have lung disease, so lung shadows obscure echocardiographic views, thus making accurate examination difficult. Transesophageal echocardiographic examination circumvents this problem and is therefore an important tool for evaluating ventricular pump function in critically ill patients.9–11

Definition of Cardiac Function and Its Relation to Venous Return

The pump function curve of the entire heart is illustrated as the relation between cardiac output and Pra over a range of values (Fig. 22-1A). Sometimes this relation is called a Starling function curve, although this term has been applied historically to a pump function curve where stroke work is the output.12 The relation between cardiac output and Pra importantly illustrates that increasing Pra is more effective in increasing cardiac output at low values than at high values of Pra.

Most physicians are aware that increased contractility improves cardiac and ventricular pump function by shifting the pump function curve upward and to the left so that, at the same filling pressure, an increased cardiac output is generated. It is equally important to realize that abnormalities in diastolic stiffness, afterload, valve function, and heart rate can shift this relation, and these factors are often more important than changes in systolic function in modulating ventricular dysfunction encountered in the noncoronary care ICU.

Control of Ventricular Pumping Function

The ventricular pump function curve can be altered by changes in contractility, preload, afterload, heart rate and rhythm, and valvular function. Consider the pressure-volume relation of the left ventricle shown in Fig. 22-2. All end-systolic pressure-volume points lie along a line, the end-systolic pressure-volume relation (ESPVR). All ejections from different diastolic volumes end on the ESPVR.13 The ESPVR shifts to the left when contractility increases, resulting in increased ejection at any given afterload; conversely, a shift to the right of the ESPVR indicates decreased contractility. Because of these characteristics, the ESPVR is a good index of ventricular contractility independent of changes in preload and afterload; because this slope is maximal at end systole and has the units of elastance (E = ΔP/ΔV), it has been denoted Emax or Ees.13

This pressure-volume representation of ventricular function is related to the ventricular pump function curve in a straightforward manner (Fig. 22-3). If the diastolic pressure-volume relation is constant, afterload is constant and if heart rate is constant, an increase in contractility decreases ESV and results in an increased stroke volume and cardiac output at the same filling pressure. Accordingly, an increase in ventricular contractility results in a leftward and upward shift of the ventricular pump function curve. An increase in contractility from a normal steep ESPVR does not decrease ESV much and therefore does not improve the ventricular pump function much (Fig. 22-4). This explains why increased contractility is only a minor contributor to regulation of ventricular function in normal human beings. In contrast, when ventricular contractility is decreased, as indicated by a decrease in slope of the ESPVR, an increase in contractility significantly decreases ESV to improve ventricular pump function (see Fig. 22-4), thereby explaining why positive inotropic agents are useful in acute treatment of dilated cardiomyopathies.

A decrease in pressure afterload will result in a decrease in ESV, so stroke volume and cardiac output increase when contractility, the diastolic pressure-volume relation, and heart rate are constant.13 Thus, decreased afterload also improves ventricular pump function by shifting the function curve up and to the left. Analogous to the effects of changing contractility, normal hearts with steep ESPVRs do not eject substantially further with a decrease in afterload because ESV does not decrease much (Fig. 22-5). This explains the observation that decreasing afterload in normal patients does not substantially increase cardiac function and output but leads to hypotension. However, in patients with depressed contractility, as signaled by a decreased slope of the ESPVR, a small decrease in afterload causes greater ejection to a smaller ESV so that stroke volume and cardiac output are substantially increased at the same ventricular filling pressure (see Fig. 22-5). Therefore, in patients with depressed systolic contractility, afterload reduction is an effective means for improving ventricular pump function.14,15

Increased stiffness of the diastolic pressure-volume relation reduces stroke volume because EDV is decreased at the same ventricular filling pressure independent of contractile state, afterload, and heart rate (Fig. 22-6). Therefore, an increase in stiffness of the diastolic left ventricle leads to a rightward and downward shift of the ventricular pump function curve.16 This may be erroneously interpreted as decreased ventricular contractility when, in this case, depressed ventricular function is completely accounted for by increased ventricular diastolic stiffness. An increase in heart rate also may shift the ventricular pump function curve to the left and upward. However, when heart rate increases, stroke volume often decreases because there is less time for the ventricle to fill during diastole, so EDV decreases. Ultimately, when there is no other change in the factors driving venous return, heart rate increases cardiac output only slightly at heart rates slower than 100 beats/min and has essentially no effect on cardiac output at faster heart rates.17 At very fast heart rates exceeding 150 beats/min, diastolic filling becomes markedly impaired, and cardiac output decreases as heart rate quickens further. When control of heart rate is abnormal due to abnormal pacemaker function or abnormal cardiac rhythm, inappropriately slow heart rates become important and can limit cardiac output. For example, if a patient is hypotensive and critically ill to the extent that heart rate is expected to be 100 beats/min but the patient is able to generate a heart rate of only 50 beats/min, then artificially increasing heart rate will substantially improve cardiac output.

Control of Venous Return by the Systemic Vessels

Cardiac function is tightly coupled to venous return, and many patients with presumed cardiac dysfunction instead have abnormalities of the factors driving venous return.18 Pra and cardiac output define the cardiac function curve and define the venous return relation.19  Figure 22-1B shows that, as Pra is decreased, venous return increases, because the pressure driving venous return back to the heart, mean systemic pressure (Pms) minus Pra, increases. The factors that determine venous return are Pms, Pra, and resistance to venous return (RVR).

In steady state, the cardiac function curve and the venous return curve are necessarily coupled because cardiac output must equal venous return. Thus the operating point of the heart is not defined by the cardiac function curve or by the venous return curve but by the intersection of these two curves (see Fig. 22-1C). Accordingly, patients with cardiovascular dysfunction having abnormal values of heart rate, Pra, aortic pressure, and cardiac output may have cardiac dysfunction that accounts for these abnormalities or may have abnormalities of venous return. It follows that, in every patient with suspected abnormal cardiovascular function, one should consider cardiac function and venous return in attempting to understand the abnormality.18,20

In health, cardiac output is controlled by mechanical properties of the systemic vessels adjusted by neurohumoral reflexes; when output and blood pressure decrease, baroreceptor reflexes act to increase flow by raising Pms by sympathetic nervous and humoral output. The importance of factors driving venous return is evident during exercise or even during the act of standing up. Without increased venous tone (as can occur with some spinal cord injuries) or increased muscle activity aided by venous valves, cardiac output and therefore blood pressure decrease precipitously in changing from a recumbent to an upright position. As an extension of normal physiology, in critically ill patients without a previous history of cardiac dysfunction, the major factor limiting cardiac output is often limited venous return. Only in patients with marked ventricular dysfunction is cardiac output limited by decreased pump function. Knowing this avoids incorrect diagnosis and treatment. For example, positive inotropic drugs (dopamine and epinephrine) increase cardiac output even in patients with no ventricular dysfunction by increasing venous return due to increased Pms and decreased resistance to venous return (by redistributing blood flow to vascular beds with short transit times). This improvement in cardiovascular function is often attributed to improved cardiac function. Yet this interpretation is often incorrect and may delay therapy aimed at correcting factors governing venous return, such as plasma volume expansion, whereas the vasoactive drugs ineffectively flog the empty heart.

In summary, a complete evaluation of the contribution of ventricular dysfunction to cardiovascular performance in critical illness acknowledges that cardiac output and ventricular filling pressures depend as much on factors driving venous return as on cardiac function. Most critically ill patients without a history of cardiac disease have abnormalities of venous return in excess of abnormalities of cardiac function. Accordingly, cardiac output is limited by the heart only in patients with marked ventricular dysfunction, and the ventricular pump function curve is dependent not only on contractility but also on afterload, the diastolic ventricular pressure-volume relation, and heart rate.

This section addresses the diverse acute and chronic etiologies of left ventricular dysfunction and concludes with principles of management for each.

Decreased Left Ventricular Systolic Function

Chronic Causes

Dilated cardiomyopathies are the best-known chronic causes of decreased left ventricular contractility.21 Dilated cardiomyopathy is often idiopathic with evidence that genetic, viral, and immune factors contribute. Dilated cardiomyopathy may also be associated with coronary artery disease, presumably due to previous ischemic events and subsequent adverse remodeling and apoptosis of cardiomyocytes leading to a dilated, poorly functional left ventricle.22 Alcoholic cardiomyopathy is an important cause of chronic dilated ventricular dysfunction to be considered in critically ill patients.21 Particularly in younger patients, inflammatory cardiomyopathy (myocarditis), usually viral, is an important cause of acute dilated cardiomyopathy that may lead to a chronic dilated cardiomyopathy in 10% of cases. Evidence of familial occurrence of similar disease is common, suggesting a genetic contribution in up to 25% of cases.21,23 Rare causes such as the glycogen storage diseases also may be found in young patients. Multiple, less common causes may be encountered (Table 22-1).

These multiple, different etiologies of dilated cardiomyopathy lead to decreased ventricular contractility in a number of ways. Loss of myocardium with degradation of the normal collagen architecture by matrix metalloproteinases and replacement with fibrous connective tissue leads to remodeling and decreased contractility.24 Increased levels of circulating renin, angiotensin II, endothelin, and norepinephrine promote cardiomyocyte hypertrophy, apoptosis, myocardial fibrosis, and vascular cell hypertrophy. Myocardial norepinephrine stores are depleted and β-receptor density is reduced in chronic dilated cardiomyopathy.24,25 Biochemical changes that may contribute to decreased contractility include decreased efficiency of the sarcoplasmic reticulum calcium pump, decreased actin-myosin adenosine triphosphatase activity, and change in myosin isoenzyme composition.

Acute Causes

In the ICU, acute causes of decreased left ventricular contractility are important because the acute causes are potentially reversible (Table 22-2). Acute causes of depressed left ventricular contractility include ischemia, hypoxemia, respiratory acidosis, metabolic acidosis, ionized hypocalcemia, hypo- and hyperthermia, exogenous toxins such as alcohol and drugs, endogenous toxins such as circulating depressant factors of sepsis, inflammatory cytokines, and increased nitric oxide (NO) production.

Myocardial Ischemia

Transient ischemic episodes occur frequently in critically ill patients. The onset of ischemia is due to myocardial oxygen demand exceeding the ability of the myocardium to extract oxygen from the oxygen supply (coronary blood flow multiplied by arterial oxygen content). Myocardial oxygen demand is increased by increasing heart rate, contractility, afterload, preload, and the basal metabolic rate of the myocardium (which increases with increased sympathetic tone and catecholamines).26 Many of the underlying illnesses encountered in the critically ill and many of the therapies, including fluid and inotropic or vasoactive drug infusion, contribute to markedly increased oxygen demand. Because of the prevalence of coronary artery disease in older patient populations, ischemia in the ICU is frequently regional with associated wall motion abnormalities. Accordingly, a high index of suspicion and an early aggressive diagnostic approach are indicated and facilitate the early treatment of ischemic coronary artery disease, as discussed in more detail in Chap. 25.

Myocardial Hypoxia

In the absence of coronary artery disease, critically ill patients with sepsis also may manifest global heterogeneous left ventricular hypoxia with increased creatine kinase MB and troponin levels. The heart consumes less lactic acid and may produce lactic acid.27 If inadequate oxygen delivery in relation to demand is not corrected quickly, then the heart may enter a detrimental positive-feedback loop of decreasing contractility, decreasing cardiac output and coronary perfusion, and, hence, decreasing contractility leading to precipitous cardiac arrest.28 In the canine model, this vicious cycle occurred when arterial O2 saturation decreased below 75% (arterial partial pressure of O2 = 40 mm Hg) when hemoglobin concentration was 14 g/dL. Accordingly, aggressive measures to prevent this level of hypoxemia by keeping arterial O2 saturation above 85% to 90% are indicated; maintaining a reasonable hematocrit in hypoxic critically ill patients with risks for myocardial ischemia is part of this therapy.

Myocardial Acidosis

Respiratory acidosis results in myocardial intracellular acidosis, and intracellular acidosis decreases the effect of intracellular calcium on the contractile proteins so that contractility is decreased.29 In critically ill patients, respiratory acidosis may significantly contribute to depressed contractility and reduced cardiac output at partial pressure of CO2 (PCO2) levels of 60 mm Hg and certainly by PCO2 levels of 90 mm Hg.30 Whether long-term elevations in PCO2 have the same myocardial depressant effect is uncertain because intracellular pH will normalize, despite high PCO2, over time. These considerations may be particularly important in patients in whom the clinician actually seeks a high PCO2 during mechanical ventilation (permissive hypercapnia) to minimize ventilator-associated lung injury (see Chaps. 37, 38, and 40).

Metabolic acidosis also may decrease left ventricular contractility, but its effects are less marked. Arterial blood gas measurement identifies metabolic acidosis in the extracellular compartment. The intracellular compartment is affected to the extent that the metabolic acid anion permeates the cell. Common organic acids such as lactic acid and ketoacids have anions that do not easily cross into the intracellular compartment, so a severe metabolic acidosis may not be associated with significant intracellular acidosis and therefore may not depress ventricular contractility much. For example, lactic acidosis at a normal PCO2 begins to depress contractility at pH 7.1 to 7.2, but even at a pH of 7.0 the depression in contractility remains quite small.31

Ionized Hypocalcemia

During septic shock and in patients critically ill from diverse causes, serum ionized calcium levels are often low.32 Further acute reductions may result in a substantial decrease in left ventricular contractility. Decreased extracellular ionized calcium concentration results in decreased calcium flux during systole and decreased contractility.33 After transfusion of red blood cells stored in standard citrated media, serum ionized calcium levels can decrease dramatically because calcium is bound by citric acid. During shock and other conditions, lactic acid, like citric acid, also appears to bind ionized calcium.34 Bicarbonate infusion also can rapidly decrease ionized calcium levels and, as a result, may depress ventricular contractility.35 In addition to ionized hypocalcemia, other electrolyte abnormalities, including hypophosphatemia, hypomagnesemia, and hypokalemia or hyperkalemia, may contribute to decreased contractility or, more importantly, to arrhythmias.

Side Effects of Common Drugs

Exogenous toxins may result in acutely depressed myocardial contractility. Ethanol is a commonly encountered substance that acutely depresses contractility. Drugs commonly used in the ICU that significantly depress contractility include β blockers, calcium channel blockers, and antiarrhythmics such as disopyramide and procainamide.

Septic Shock and Systemic Inflammatory Responses

Many inflammatory pathways triggered by bacterial endotoxins and sepsis have been suggested to contribute to myocardial dysfunction of sepsis. A number of proinflammatory cytokines, including tumor necrosis factor α (TNF), interleukin (IL)–1, IL-2, and IL-6, decrease myocardial contractility in humans and in animal models of sepsis.36,37 Proinflammatory cytokines trigger increased NO production. NO is normally an important regulator of beat-to-beat contractility and, in the setting of enhanced NO production, becomes an important myocardial depressant factor.37 Reactive oxygen intermediates released by leukocytes and cardiomyocytes contribute directly, and by formation of peroxy nitrite radicals, to myocardial damage and dysfunction. Coronary capillary endothelial activation, damage, and dysfunction also contribute, in part due to impaired regulation of coronary microvascular blood flow, which impairs myocardial oxygen extraction.38 Thus, multiple pathways of the intramyocardial inflammatory response may contribute to myocardial dysfunction of systemic inflammation and sepsis.

During hyperdynamic sepsis, the etiology of the hypoperfusion state likely resides in the septic paralysis of arteriolar (and in part venular) smooth muscle, with a minor contribution from decreased contractility, because cardiac output is maintained or elevated. However, the late decrease in cardiac output leading to death involves significant decreases in systolic contractility and increases in diastolic stiffness.

During anaphylactic shock, histamine depresses left ventricular contractility in human beings,39 although the primary cause of hypoperfusion is hypovolemia (see Chap. 106). Hyperthermia and hypothermia may decrease myocardial contractility and contribute to depressed left ventricular function observed during sepsis and other critical illnesses associated with marked abnormalities of body temperature (see Chaps. 110 and 111).

Management of Decreased Left Ventricular Contractility in Critical Illness

Identify and Correct Acute Reversible Causes

It is important to identify the multiple, different potentially reversible causes for depressed contractility in critically ill patients because, although alone they may be insufficient to account for the left ventricular dysfunction, together they may significantly depress function. For example, if ischemia or hypoxemia is present, aggressive attempts to correct it should be instituted. In the presence of coronary artery disease, standard care including heparin, antiplatelet therapy (when indicated), β blockade, and coronary vasodilation using nitrates may be helpful. Thrombolytic therapy within 4 to 6 hours of acute coronary thrombosis or emergency angioplasty decreases the incidence of congestive heart failure and improves outcome (see Chap. 25). Correction of hypoxemia and anemia may result in substantial improvement in ventricular function. Attention should be paid to decreasing factors that increase myocardial oxygen demand. Therefore, when β blockade is not feasible, choosing the lowest level of inotropic and vasoactive drugs that produces the desired therapeutic effect will minimize their contribution to myocardial oxygen demand. Likewise, alleviating pain is important to diminish the associated tachycardia and increased sympathetic tone.

In ventilated patients with left ventricular dysfunction, the detrimental effects of acute respiratory acidosis should be considered; mixed venous and, hence, tissue PCO2 is much higher than the arterial partial pressure of CO2 when the cardiac output is low. In general, metabolic acidosis should be treated by reversing its etiology. Alkali therapy for increased anion gap metabolic acidosis is of no benefit and may be dangerous even at pH values as low as 7.0 for a number of reasons.35 Bicarbonate infusion results in an increase in PCO2 due to chemical equilibrium of HCO3− with H2O and CO2 unless compensatory hyperventilation is also instituted. Particularly during rapid bolus injection, local PCO2 may climb to extremely high values so that myocardial intracellular acidosis transiently may be severe, leading to decreased ventricular contractility.30 Bicarbonate therapy is associated with an increase in lactic acid production because bicarbonate increases the rate-limiting step of glycolysis. Bicarbonate therapy also decreases blood levels of ionized calcium.34,35

Decreased contractility due to ionized hypocalcemia can be corrected with an intravenous infusion of calcium. After approximately 6 U of transfusion, ionized hypocalcemia should be measured and corrected, if necessary. Hypophosphatemia, hypomagnesemia, hypokalemia, hyperkalemia, and other metabolic disturbances also should be corrected because they may lead directly or indirectly to altered cardiovascular function.

Treatment of myocardial depression due to circulating myocardial depressant factors has been attempted with antibodies to endotoxin and TNF, naloxone, and dialysis, but these investigational treatments have not led to improved clinical outcomes. Inhibitors of circulating inflammatory mediators appear to be beneficial in severe sepsis but are limited in less severe sepsis,40 possibly because circulating factors (endotoxin, TNF, and IL-1) are present for only limited periods early in the course of sepsis. Naloxone administered over short periods is not consistently effective, but longer-duration infusions of 1 or more days may result in improvement of hemodynamic measurements. Dialysis, hemofiltration, and plasmapheresis have not been tested adequately in human septic shock, but preclinical evidence suggests that depressed left ventricular contractility due to a myocardial depressant factor of sepsis can be reversed with these treatments.41

Managing the Depressed Heart

Having reversed the acute contributors to depressed left ventricular contractility, standard therapy of decreased left ventricular contractility includes optimizing ventricular filling pressure, decreasing afterload using angiotensin-converting enzyme inhibitors or alternatives when arterial pressure is adequate, increasing contractility using inotropic agents, resynchronization therapy using biventricular pacing,42,43 and, when appropriate, using intraaortic balloon counterpulsation followed by surgical correction of coronary artery stenosis or other surgically correctable lesions24,44 (see Chap. 23).

The ventricular pump function curve illustrates the Frank-Starling mechanism, which shows that increased ventricular filling results in increased ejection even when contractility is depressed. The limit to increased ventricular filling is generally set by the onset of pulmonary edema. Pulmonary edema fluid enters the lung interstitium according to the Starling equation. At normal protein osmotic pressures (largely due to albumin) and normal permeability of the pulmonary endothelium, pulmonary edema starts to develop at Ppw values of at least 20 to 25 mm Hg.45 In the presence of decreased oncotic pressure due to decreased albumin or in the presence of a leaky pulmonary endothelium, pulmonary edema may form at considerably lower Ppw values; in acute respiratory distress syndrome (ARDS) or pneumonia, pulmonary edema may form at very low Ppw values. With this in mind, it is appropriate to search for the Ppw that produces the highest cardiac output without resulting in substantial pulmonary edema. Most often, this search necessitates preload reduction using diuretics and vasodilating agents (Table 22-3). However, when pulmonary edema does not limit oxygenation, it is appropriate to consider increasing cardiac output by intravascular fluid expansion.

Further management of decreased ventricular contractility then proceeds with afterload reduction14 and inotropic agents.46,47 These therapies are considered in detail below (Acute on Chronic Heart Failure). When vasodilator and inotropic therapy is insufficient, temporary support using intraaortic balloon counterpulsation is appropriate when damaged myocardium is expected to recover or as supportive therapy leading to surgical correction of an anatomic abnormality.24,44 Balloon inflation during diastole improves diastolic perfusion of the coronary and systemic arterial beds. During systole, deflation of the balloon reduces afterload, allowing for increased ejection by a ventricle with markedly decreased contractility (see Chap. 25). Stem cell transplantation is a promising new approach under investigation to repair damaged myocardium.48

Increased Diastolic Stiffness

In normal hearts and in hearts with depressed ventricular function, increasing preload is an important mechanism of increasing cardiac output. For hearts with normal systolic function, left ventricular end-diastolic filling pressures are often in the range of 0 to 10 mm Hg and result in an adequate cardiac output. For hearts with depressed contractility, higher filling pressures are usually required for an adequate cardiac output. Therefore, there is no uniformly optimal filling pressure. Left ventricular function may be substantially impaired by increased diastolic stiffness of the left ventricle—a shift up and to the left of the diastolic pressure-volume relation.16,49 This is a problem whose importance is equal at least to depressed contractility in the critically ill patient.8 Depressed systolic function reduces stroke volume because ESV increases; in contrast, increased diastolic stiffness reduces stroke volume because EDV decreases. Increased diastolic stiffness is a relatively frequent problem encountered in critically ill patients. It differs from depressed ventricular contractility because it is much more difficult to treat and does not respond to conventional therapy of decreased left ventricular pump function.50 In fact, in the absence of an imaging study that demonstrates increased diastolic stiffness (small EDV in relation to the end-diastolic pressure [EDP]), the diagnosis of increased diastolic stiffness is suggested by finding depressed ventricular pump function unresponsive to fluid loading, afterload reduction, and inotropic agents. Occasionally, the diagnosis of increased diastolic stiffness is suggested by the observation that cardiac output is unusually sensitive to changes in heart rate.

Chronic Causes

Chronic diseases that increase diastolic stiffness include concentric left ventricular hypertrophy due to hypertensive cardiovascular disease, hypertrophic cardiomyopathy, and restrictive myocardial diseases. In addition, diseases of the pericardium, including constriction and effusion, and other processes that increase intrathoracic pressure result in increased diastolic stiffness, as discussed in Chap. 28. Concentric hypertrophy due to chronic hypertension is very common; although it seldom primarily accounts for severe depression in ventricular pump function, it may be an important contributor in combination with acute diseases depressing systolic function. Hypertrophic cardiomyopathy results in increased diastolic stiffness and, in the setting of hypovolemia, may also result in greatly increased afterload due to dynamic aortic outflow obstruction. Over a period of days and months, β blockers and calcium channel blockers, in particular verapamil, may reduce evidence of increased diastolic stiffness. More rapidly, these agents alleviate dynamic outflow obstruction in patients with hypertrophic cardiomyopathy due to their negative inotropic effect.51 Restrictive cardiomyopathies include amyloidosis, hemochromatosis, sarcoidosis, endomyocardial fibrosis, some glycogen storage diseases, and restriction because of surgical correction of acquired and congenital abnormalities. Amyloidosis is uncommon at age 40 but by age 90 has a prevalence of 50%.

Clinical examination may show a Kussmaul sign, rapid x and y descents in the jugular venous pressure waveform so that a and v waves are prominent, and a fourth heart sound. Hepatojugular reflux may be prominent because the increased venous return produced by this maneuver cannot be accommodated by the stiff heart. Diastolic ventricular pressure measurements may show a square root sign, which is a rapid early rise in diastolic pressure to a relatively constant plateau. Echocardiographic evaluation may demonstrate rapid early diastolic filling to a relatively fixed diastolic diameter similar to the square root sign, and increased myocardial echogenicity may be observed in amyloidosis.52,53

Acute Causes

As with diseases resulting in depressed left ventricular systolic function, it is important to consider the acute, potentially reversible causes of increased diastolic stiffness.8 Regional or global ischemia results in delayed systolic relaxation, contributing to increased diastolic stiffness. This change in diastolic stiffness usually precedes depressed contractility because the sarcoplasmic reticulum calcium pump has a lower affinity for adenosine triphosphate than do the contractile proteins. In addition, ischemia may result in increased diastolic stiffness by increasing pericardial pressure as a result of increased CVP.54 Therefore, in the setting of increased diastolic stiffness, any ischemia should be treated aggressively.55 Nitrates increase coronary blood flow and decrease tone in the venous capacitance bed, thereby reducing pericardial pressure; nitroprusside also decreases diastolic stiffness.

Increased intrathoracic or intrapericardial pressure is a common reversible cause of apparent increased diastolic stiffness in critical illness. Intrathoracic pressure is increased by positive-pressure mechanical ventilation and more so by the addition of positive end-expiratory pressure (PEEP). Positive airway pressures and PEEP are variably transmitted to the heart, depending on the distensibility of the lungs and chest wall. If the lungs are very distensible and the chest wall is relatively rigid (as with a tense abdomen), then most of an increase in airway pressure will be transmitted to the heart; to maintain the same chamber volumes, the atrial and ventricular pressures have to increase as much. This accounts for part of the reduction in venous return and cardiac output if and when Pms does not increase by a similar amount. A common misconception is that, if the lungs are very stiff, as in the early exudative phase of ARDS, then less of an increase in airway pressures will be transmitted to the heart. However, because PEEP reduces shunt by re-aerating flooded lung regions, the chest wall volume and pleural pressure increase as much or more in ARDS, so the increase in Pra with PEEP may be just as much as in patients with normal lungs. Increased intrathoracic pressure due to pneumothorax or massive pleural effusion may tamponade the heart and thereby result in apparent increased diastolic stiffness. Greatly increased intraabdominal pressure may elevate the diaphragm and similarly increase diastolic stiffness. Pericardial pressure may be increased by pericardial effusion and rarely by massive pneumopericardium. Because all these causes of increased intrathoracic or intrapericardial pressure leading to apparent increased diastolic stiffness are treatable, they must be identified or excluded early in critically ill patients.

Hypovolemic shock and septic shock may result in increased diastolic stiffness.56 The increased diastolic stiffness associated with these kinds of shock is associated with irreversibility of the shock state and increased mortality rate. In septic shock, when depressed left ventricular systolic contractility occurs, the response of surviving patients is that of decreased diastolic stiffness or increased diastolic ventricular compliance.57 This is the usual response to decreased left ventricular systolic contractility seen with other dilated cardiomyopathies.58 However, in patients with septic shock who do not survive, the diastolic left ventricles do not dilate to increase EDV and, hence, do not compensate normally for decreased systolic contractility. The diastolic ventricles of those who do not survive are therefore much stiffer than the ventricles of those who do survive.59 Infusion of catecholamines and calcium may further contribute to increased diastolic stiffness by contraction band formation.

Hypothermia with body temperature falling below 35.8°C (95.8°F) also results in increased left ventricular diastolic stiffness. This is a reversible phenomenon as temperature is increased. This is an important consideration during massive fluid resuscitation and mandates resuscitation with warmed infusions.

Management of Diastolic Dysfunction

Whereas acute diastolic stiffness due to ischemia, tamponade, and tension pneumothorax are readily treated, acute therapy to reverse diastolic stiffness in the critical care setting is limited. Therefore, searching for an optimal filling pressure that maximizes ventricular diastolic filling without resulting in substantial pulmonary edema is a critically important component of care in these patients. In addition, hypovolemia and sepsis should be treated aggressively and promptly, inotropic agents should be avoided or used at the smallest dose that results in the desired systolic or vascular effect, hypothermia should be prevented and treated, and tachycardia or atrioventricular arrhythmias should be treated early (see below). Intrathoracic pressure is minimized by appropriate ventilator management and by decompressing surrounding compartments (pericardial, pleural, and abdominal) when these cause cardiac tamponade.

Special Effects of Altered Afterload on Ventricular Function in Critical Illness

An increase in afterload decreases left ventricular pump function because stroke volume is reduced as a result of increased ESV (see Fig. 22-2). In malignant hypertension, elevated aortic pressure results in decreased cardiac output and elevated left ventricular filling pressures leading to pulmonary edema even if contractility is normal. Antihypertensive therapy results in rapid improvement. When contractility is depressed, increased afterload may worsen cardiac function even more. This is particularly important in dilated cardiomyopathies, in which increased afterload may be observed due to increased sympathetic tone, activation of the renin-angiotensin-aldosterone axis, and abnormally increased vascular smooth muscle tone.

Aortic valvular stenosis or dynamic obstruction of the aortic outflow tract also may increase afterload and contribute to decreased left ventricular pump function14 (see Chap. 29). Dynamic outflow tract obstruction is most commonly due to hypertrophic cardiomyopathy. However, patients with preexisting concentric hypertrophy due to chronic hypertension who have a decrease in intravascular volume may develop dynamic aortic outflow tract obstruction with the classic findings of systolic anterior motion of mitral valve leaflet, increased ejection velocities signifying increased gradients across the aortic outflow tract, and cavity obliteration at end systole. This appears to occur most commonly in elderly patients with previously treated hypertension. Volume infusion to reverse intravascular hypovolemia may prevent left ventricular cavity obliteration and outflow tract obstruction and thereby reduce ventricular afterload. It is important to identify outflow tract obstruction as the cause of increased afterload because this cause of increased afterload is worsened by conventional afterload reduction therapy.

When afterload is reduced dramatically, or when intravascular volumes are expanded, the resulting high cardiac output state is sometimes called high-output cardiac failure. Actually, cardiac function still lies on a normal cardiac function curve, but the greatly increased venous return associated with low afterload results in high right- and left-side filling pressures with the appearance of right- and left-side congestion. This is particularly apparent in the presence of atrioventricular valvular stenosis, which previously may have been occult. Causes of high-output failure include anemia, arteriovenous fistulas, hepatic failure, Paget disease, thyrotoxicosis, pregnancy, carcinoid syndrome, and renal cell carcinoma.

Abnormal Heart Rate and Rhythm

Normally, heart rate and contractile states are matched to venous return and afterload to maximize the efficiency of the cardiovascular system. Even though heart rate is often of lesser importance in trying to increase cardiac output, excessively fast or excessively slow heart rates may limit cardiac output. Bradycardia is an important abnormal rhythm in a critically ill patient. Primarily, it is important to determine whether hypoxemia, drugs such as acetylcholinesterase inhibitors, or other reversible insults are the cause of bradycardia. In these cases, treatment consists of rapid reversal of the cause. In other cases in which bradycardia is due to primary cardiac disease, including myocardial infarction with involvement of the conducting system, therapy is directed at increasing heart rate by other means. Acutely, bradycardia may be treated with atropine and, if necessary, by isoproterenol or epinephrine infusion titrated to heart rate response. These temporizing measures allow placement of temporary or permanent pacemakers. In addition to the well-known indications for temporary pacing after myocardial infarction, it should be recognized that symptomatic bradycardia from any cause is an indication for pacing.

Tachycardia at sufficiently high rates results in an inadequate diastolic filling time, so stroke volume is reduced because adequate diastolic filling does not occur and the contribution to ventricular diastolic filling by the atria is less efficient, particularly in atrial fibrillation. An end-diastolic gradient across the mitral valve develops at fast heart rates. Hypoxemia and acidosis encountered in critically ill patients are frequently associated with ventricular and, even more commonly, supraventricular tachyarrhythmias. Hyperkalemia and hypokalemia, hypocalcemia, and hypomagnesemia are common electrolyte disturbances associated with increased incidence of ventricular arrhythmias. Accordingly, management of atrial and ventricular tachyarrhythmias involves correcting these potential contributing abnormalities.

Cardiac resynchronization therapy using biventricular pacing appears to improve cardiac function in patients having a decreased ejection fraction, bundle branch block, and New York Heart Association class III or IV heart failure.42,43 The role for resynchronization therapy in the critical care setting has not been fully defined.

Arrhythmias including atrial fibrillation, atrial flutter, and ventricular tachycardia should be immediately cardioverted if they are contributing to a shock state. Otherwise, rapid heart rate due to atrial fibrillation is slowed using β blockers or second-line agents including calcium channel blockers. Adenosine, verapamil, and maneuvers to increase vagal tone may be useful in the diagnosis of tachyarrhythmias and in treating paroxysmal supraventricular tachycardia.60 Multifocal atrial tachycardia responds to correction of underlying pulmonary disease and to verapamil.61 Ventricular dysrhythmias contributing to altered hemodynamic function must be treated. Specific management of ventricular arrhythmias is detailed in Chap. 24.

Valvular Dysfunction

The valves regulate preload and afterload and are therefore important determinants of left ventricular pump function (see Chap. 29). In critically ill patients, the effect of preexisting valvular disease may change with altered hemodynamics, or the extent of valvular disease may change primarily. For example, aortic and mitral insufficiencies contribute to low cardiac output at high ventricular filling pressures in critical illness, and both respond quickly to afterload reduction. Moreover, mitral regurgitation may worsen acutely due to increased EDV and expansion of the mitral annulus. In contrast, mitral valve prolapse may worsen at low ventricular volumes due to hypovolemia. In high cardiac output states, previously insignificant mitral stenosis may result in a high Pla and pulmonary edema. The gradient across the stenotic aortic valve may increase in high-flow states and conversely decrease in low-flow states, so that, without considering the flow across the valve, an incorrect judgment of the functional significance of the valvular disease may be made. Dysfunction of prosthetic valves is important to identify and may be a surgical emergency.

Right ventricular pump function also depends on contractility, afterload, preload (the diastolic pressure-volume relation), heart rhythm, and valve function. However, the right ventricle differs from the left ventricle, so the relative importance of each of these components is different. The left ventricle is well designed to generate high pressures. Its thick walls and small chamber volume result in manageable levels of wall stress despite high intracavitary pressures. The helical arrangement of muscle fibers changing from endocardium to epicardium in concentric layers results in a strong wall with an efficient distribution of wall stress.62 In contrast, the right ventricle is a thin-walled pump whose surface has a large radius of curvature and it is not suited as a high-pressure generator. Instead, the right ventricle functions as an excellent flow generator at low pressures. Right ventricular contraction moves sequentially from the apex to the pulmonary outflow tract, giving it features of a peristaltic volume pump. During diastole, the right ventricle at normal diastolic pressure lies below its stressed volume, a feature that allows it to accommodate a large filling volume without an elevation in EDP. Because of these features, volume preload and, most importantly, pressure afterload become even more important determinants of right ventricular function than they are in the left ventricle.

Decreased Right Ventricular Systolic Function

Contractility of the right ventricle is decreased approximately to the same extent as in the left ventricle by the many causes listed for the left ventricle (see Tables 22-1 and 22-2). Occasionally, right ventricular contractility is disproportionately reduced as in right ventricular infarction, right ventricular dysplasia, Uhl anomaly, isolated right ventricular myopathy, and myopathy associated with uncorrected atrial septal defect. Right ventricle ischemia in the absence of coronary artery disease is very important during critical illness. When afterload is elevated, the right ventricle responds along a preload-dependent right ventricular systolic pressure-volume relation, so right ventricular ESV increases.63 Right ventricular chamber pressures are increased, the radius of curvature is increased, and, hence, the wall stress in the thin right ventricular wall increases dramatically. Therefore, right ventricular myocardial oxygen demand increases proportionately. At increased right ventricular pressures, the right ventricular intramural pressure increases, and hence, the gradient for right ventricular coronary blood flow decreases. Oxygen supplied to the right ventricular myocardium may not meet oxygen demand, so contractility decreases, further worsening right ventricular function.64

Disorders of Right Ventricular Preload, Afterload, Rhythm, and Valves

Increasing right ventricular EDV results in an increase in right ventricular stroke volume, even though right ventricular EDP may not increase much because normally EDV is below the right ventricular diastolic stressed volume. Because of this, and because Pra is heavily influenced by intraabdominal, intrathoracic, and intrapericardial pressures, Pra (CVP) is probably a poor indicator of right ventricular preload.

The afterload of the right ventricle is the Ppa (Table 22-4). This may be elevated long term by emphysematous destruction of small pulmonary vessels, chronic hypoxic pulmonary vasoconstriction due to obstructive pulmonary disease and restrictive chest wall diseases, recurrent pulmonary embolism, chronically elevated Pla due to mitral stenosis or left ventricular congestive failure, primary pulmonary hypertension, and several connective tissue and inflammatory diseases that involve the pulmonary vasculature. The acute pulmonary vasodilator response to nitroglycerin infusion is useful for predicting which patients will do well.15 Acute causes of pulmonary hypertension are also important to identify because they are more often reversible. In addition, whereas the right ventricle may hypertrophy and accommodate severe chronically increased afterload, moderate acute pulmonary hypertension may rapidly lead to right ventricular decompensation. Important causes of acute pulmonary hypertension in critically ill patients include pulmonary embolism, hypoxic pulmonary vasoconstriction, acidemic pulmonary vasoconstriction, pulmonary infection, ARDS, sepsis, and acutely elevated Pla (see Chap. 26).

As with the left ventricle, the right ventricle depends on normal rate and rhythm to attain optimal function. Right ventricular valvular disease is less common and less important than left ventricular valvular disease because right ventricular pressures are much less than left ventricular pressures, so gradients across the valves are considerably less. In critically ill patients, tricuspid valve disease with endocarditis is common as a preexisting condition such as endocarditis or as a result of instrumentation with a pulmonary artery catheter or other right heart catheters.

Ventricular Interaction

Diagnosis of Ventricular Interdependence

Combined pump dysfunction of the right and left ventricles is more common than isolated right or left ventricular pump dysfunction. Part of the explanation is that the diseases resulting in decreased pump function more commonly involve both ventricles. However, the right and left ventricles interact in important ways that, when recognized, may lead to a more effective therapeutic approach. The right and left ventricles are contained inside the same pericardial cavity within the chest wall, and the right and left ventricles share the interventricular septum. Accordingly, much of the interaction between the right and left ventricles is mediated by the parallel coupling produced by the pericardium and septal shift. The right ventricle is also connected in series with the left ventricle so that a substantial rise in Pla is transmitted back through the pulmonary vasculature and results in an increase in right ventricular afterload. In addition, the left ventricle is the pump that perfuses the right and left coronary circulations; hence, decreased systemic pressure combined with elevated right ventricular pressures may result in hypoperfusion of the right ventricle.

Detrimental ventricular interaction is generally only a problem when right heart and pulmonary circulation pressures are high. Table 22-4 lists a number of important and common causes in critically ill patients. Pulmonary embolus is a common and often missed diagnosis requiring helical computed tomography or pulmonary angiography. Right ventricular pressure and Pra rise. Elevated right ventricular pressure shifts the interventricular septum from right to left during diastole, resulting in increased left ventricular diastolic stiffness. During systole, left ventricular pressure usually is sufficiently greater than right ventricular pressure, so the septum shifts back. This change in systolic shape means that the myocardium of the left ventricular free wall must shorten even more for less of an ejected stroke volume. The rise in Pra is transmitted through the compliant right atrium to the pericardial space. The increase in pericardial pressure tamponades all other cardiac chambers. When pericardial effusion is present, these effects are magnified. When Pla is high due to mitral stenosis or decreased left ventricular pump function, Ppa values rise. In the long term, this also may result in increased pulmonary vascular resistance. The resulting right ventricular failure with right-to-left septal shift impairs left ventricular filling, which may be a critical insult in these diseases.

Treatment of Ventricular Interdependence

Management aims to decrease Ppa values and to decrease parallel coupling of the left and right ventricles. Reversible contributions to pulmonary hypertension are treated as outlined in the discussion of right ventricular afterload. Parallel coupling by elevated pericardial pressure is decreased by relieving pericardial tamponade, if present; by decreasing intrathoracic pressures by decompressing thoracic and abdominal fluid and air collections; by airway management to reduce Ppa; in select patients by surgically opening or removing the pericardium; and in patients after sternotomy, by leaving a sternal incision open and closing only the overlying skin.

Unresuscitatable cardiac arrest is a common outcome when perfusion of the right ventricle is threatened because right ventricular pressures are high relative to left ventricular pressures. This happens in massive pulmonary embolism and in cases of severe pulmonary hypertension. Thrombolytic therapy and pulmonary vasodilator therapy attempt to reverse the cause. Animal models of massive pulmonary embolism suggest that successful acute cardiovascular management attempts to raise systemic pressures more than right-side pressures.64 Therefore, norepinephrine or epinephrine, both of which have a substantial α-agonist effect, improves right ventricular perfusion and is more successful in immediate resuscitation than is isoproterenol or fluid infusion.

Heart failure affects almost 5 million Americans, with more than half a million new cases each year. Seventy-five percent of heart failure hospitalizations involve patients older than 65 years. Heart failure carries a poor prognosis, with a survival rate of less than 50% after 5 years.24 Mortality rate is often related to episodes of acute decompensation that punctuate the course of heart failure. Important precipitating causes of acute decompensation are listed in Table 22-5. A review of these causes shows why chronic heart failure is often exacerbated in the course of critical illness, so early detection and management of acute-on-chronic heart failure are essential components of critical care.65

Precipitating Factors

Poor compliance with medications and new medications are common precipitating events. Dietary indiscretions with increased sodium load and alcohol ingestion leading to a further acute depression in systolic contractility are seen frequently. Intercurrent illness such as a urinary tract infection or viral syndrome, fever, or high ambient temperatures may make greater demands on cardiac output than can be met. Onset may be slow, and patients complain of decreased exercise tolerance, dyspnea, paroxysmal nocturnal dyspnea, and swelling of ankles and abdomen worsening over days and weeks. Rapid onset suggests that ischemia or arrhythmia may be the cause. Cardiac output may be depressed, so the kidneys are hypoperfused. The response of the kidneys is to avidly retain sodium and water, which may further worsen volume overload. Volume overload leads to elevated venous pressures with subsequent pulmonary edema due to elevated Pla and peripheral edema due to elevated systemic venous pressures. There is an excessive reflex release of catecholamines leading to tachycardia and increased arterial tone, so arterial resistance rises. Increased arterial resistance as afterload may be detrimental to left ventricular pump function. Activation of the renin-angiotensin axis accounts for avid renal absorption of sodium. Vasopressin release increases water retention. Coronary artery disease is common in this population, so decompensation may have followed an acute ischemic coronary event or coronary ischemia may be precipitated by worsened congestive heart failure.

Clinical Features

Patients are often anxious, tachycardic, and tachypneic, with evidence of hypoperfused extremities and possibly cyanosis. Jugular veins are distended, and hepatojugular reflux may be demonstrable on physical examination. Typically the sternal angle is approximately 5 cm above the right atrium when the patient's torso is at a 30- to 45-degree angle. Jugular venous distention is usually no higher than 1 to 3 cm above the sternal angle in normal patients, but it is elevated during acute heart failure. An apical impulse lateral to the midclavicular line or farther than 10 cm from the midsternal line is a sensitive but not specific indicator of left ventricular enlargement, whereas an apical diameter larger than 3 cm indicates left ventricular enlargement.66 A sustained apical impulse suggests left ventricular hypertrophy or aneurysm. A third heart sound or summation gallop is often present but may be obscured by increased respiratory sounds. Pulse pressure is often reduced, so peripheral pulses are “thready.” Crackles are heard in dependent lung fields but in severe cardiac failure are heard in all zones. Wheezes and a prolonged expiratory phase may be noted, suggesting edema surrounding the airways. Hepatomegaly, which may be pulsatile particularly with tricuspid valve insufficiency, may be present, and there is evidence of dependent edema in the lower extremities and over the sacrum.

Chest radiographic findings suggesting elevated left ventricular filling pressures include upper zone redistribution of vascular markings, septal lines (Kerley B lines), loss of pulmonary vascular definition, perivascular and peribronchial cuffing, perihilar interstitial and then alveolar filling patterns, and pleural effusions. The cardiopericardial silhouette may be enlarged, suggesting enlarged cardiac chambers, and the azygos vein may be enlarged, suggesting elevated Pra.

Management

Therapy of acute-on-chronic heart failure initially aims to treat intravascular overload and improve gas exchange. Therefore, the patient is positioned with the torso elevated at least 45 degrees, and oxygen is administered. Good intravenous access, optimally central venous, is established. Furosemide (20 to 40 mg initially, followed by increasing doses as required) induces a rapid diuresis. Even before diuresis is established, furosemide reduces Pla by a venodilation effect and also reduces intrapulmonary shunt.67 Titrated morphine doses decrease venous tone and thereby decrease left ventricular filling pressures and improve pulmonary edema. In addition, morphine may make the patient less anxious, thereby decreasing whole-body oxygen demand. Nitrates are venodilators that serve to decrease left ventricular filling pressure and mild arterial vasodilators, resulting in decreased afterload. Nitrates have the additional benefit of being coronary vasodilators.

Afterload reduction is an important therapeutic intervention in patients with depressed left ventricular systolic contractility14 due to a decrease in the slope of the ESPVR. Because there is a decrease in the slope of this relation, small reductions in pressure afterload can result in improved ejection to smaller ESVs. The reduction in ESV results in increased stroke volume and in substantially decreased end-systolic wall stress because, by the Laplace relation, wall stress is proportional to the product of cavity pressure and radius. The decrease in wall stress reduces myocardial oxygen demand. Afterload reduction in some critically ill patients may result in unacceptable hypotension. For this reason, it is best to start with an easily titratable medication with a very short half-life such as nitroprusside or, in the setting of ischemia, intravenous nitroglycerin (see Chap. 25). Nitroprusside is infused at an increasing dose while the response of cardiac output and blood pressure is measured repeatedly, so that an optimal dose resulting in maximum cardiac output with adequate perfusing pressures is chosen. Nitroprusside and other nitrates are direct or indirect NO donors that cause vascular smooth muscle relaxation. Nitroprusside at larger doses can result in significant toxicity, with cyanide formation and methemoglobinemia. When circulatory stability is achieved, other, longer-acting agents are substituted; angiotensin-converting enzyme inhibitors are particularly useful,21,24 as are alternative drugs (see Table 22-3).

Inotropic or vasoactive agents are extremely useful in reversing depressed systolic contractility, but routine use of inotropes is not indicated for heart failure because inotropic use may increase mortality rate.47,68Dobutamine acts mainly on β1 receptors and results primarily in increased ventricular contractility and in mild peripheral vasodilation. Doses from 2 to 15 μg/kg per minute are infused through a central venous line. Particularly in the presence of intravascular hypovolemia, the vasodilating effect of dobutamine may exceed its effect on increasing cardiac output, so blood pressure may decrease unacceptably. Dopamine has significant adverse effects that should limit its use. Low-dose dopamine has been clearly shown not to be beneficial. Dopamine is predominantly a β agonist in doses of 5 to 10 μg/kg per minute; at doses exceeding 10 μg/kg per minute, dopamine is an α agonist and therefore increases arterial resistance. Dopamine increases Pms and, hence, venous return increases, resulting in increased left ventricular filling pressures. The increased afterload at large doses and increased filling pressures associated with dopamine are often undesirable in treating decreased contractility. Milrinone and enoximone are phosphodiesterase inhibitors that increase contractility by increasing intracellular calcium during systole. These agents also may result in afterload reduction and therefore may be particularly beneficial in short-term treatment of depressed contractility. The use of digoxin to increase contractility is not generally helpful in the acute setting.69

In general, although positive inotropic agents improve contractility, they do so at the cost of increased myocardial oxygen demand and decreased efficiency of oxygen use and therefore may precipitate ischemia, arrhythmias, and other adverse outcomes. Dobutamine and milrinone are superior to dopamine, epinephrine, and isoproterenol for minimizing this adverse effect. If acute decompensation leads to cardiogenic shock and recovery is anticipated after medical or surgical intervention, then intraaortic balloon counterpulsation should be instituted when afterload reduction and inotropic therapy are insufficient.