oc~LuL.auvu of excess fluid behind the failing ventricle may no
`exist. For example, patients with long-standing aortic valve
`or systemic hypertension may have ankle edema, congestive
`, and systemic venous distention late in the course of
`even though the abnormal hemodynamic burden initially
`on the left ventricle. This occurs in part because of the
`pulmonary hypertension and resultant right-sided heart fail(cid:173)
`also because of the retention of salt and water characteristic
`of heart failure (Chap. 37). The muscle bundles composing
`~enul~·"'"~ are continuous, and both ventricles share a common
`mten•enm(;UI:w: septum. Also, biochemical changes that occur
`failure and that may be involved in the impairment of myocar(cid:173)
`(Chap. 232), such as norepinephrine depletion and alter-
`the activity of myosin ATPase, occur in the myocardium of
`regardless of the specific chamber on which the abnor(cid:173)
`"'""m~m"· .. burden is placed initially.
`ARD VERSUS FORWARD HEART FAILURE For
`a controversy has revolved around the question of the
`of the clinical manifestations resulting from heart failure.
`of backward heart failure contends that in heart failure,
`other ventricle fails to discharge its contents or fails to fill
`As a consequence, the pressures in the atrium and venous
`the failing ventricle rise, and retention of sodium and
`as a consequence of the elevation of systemic venous
`pressures and the resultant transudation of fluid into the
`space (Chap. 37). In contrast, the proponents of the forward
`hypothesis maintain that the clinical manifestations of
`result directly from an inadequate discharge of blood into
`system. According to this concept, salt and water retention
`'""""',"''" of diminished renal perfusion and excessive proximal
`sodium reabsorption and of excessive distal tubular reabsorp(cid:173)
`activation of the renin-angiotensin-aldosterone system.
`distinction between backward and forward heart failure
`distinction between right and left heart failure) is artificial,
`mechanisms appear to operate to varying extents in most
`with heart failure. However, the rate of onset of heart failure
`nttue11Ce~s the clinical manifestations. For example, when a large
`of.the left ventricle is suddenly destroyed, as in myocardial
`although stroke volume and blood pressure are suddenly
`(both manifestations of forward failure), the patient may sue(cid:173)
`acute pulmonary edema, a manifestation of backward failure.
`survives the acute insult, clinical manifestations resulting
`depressed cardiac output, including the abnormal
`of fluid within the systemic vascular bed, may develop.
`in the case of massive pulmonary embolism, the right ventri(cid:173)
`and the systemic venous pressure may rise to high
`:ba1:k~vard failure), or the patient may develop shock secondary
`output (forward failure), but this low-output state may
`be maintained for some days before sodium and water retention
`to produce peripheral edema occurs.
`OF CARDIAC OUTPUT The redistri-
`
`so that the delivery of oxygen to vital organs, such as
`and myocardium, is maintained at normal or near-normal
`flow to less critical areas, such as the cutaneous and
`beds and viscera, is reduced. Vasoconstriction mediated by
`nervous system is largely responsible for this redistribu(cid:173)
`in turn may be responsible for many of the clinical manifes(cid:173)
`eart failure, such as fluid accumulation (reduction of renal
`fever (reduction of cutaneous flow), and fatigue (re(cid:173)
`muscle flow).
`
`WATER RETENTION (See also Chap. 37)
`. volume of blood pumped by the left ventricle into the
`Vascular bed is reduced, a complex sequence of adjustments
`
`CHAPTER 233
`Heart Failure
`
`1289
`
`occurs that ultimately results in the abnormal accumulation of fluid.
`On the one hand, many of the troubling clinical manifestations of
`heart failure are secondary to this excessive retention of fluid; on the
`other, this abnormal fluid accumulation and the expansion of blood
`volume that accompanies it also constitute an important compensatory
`mechanism that tends to maintain cardiac output and therefore perfu(cid:173)
`sion of the vital organs. Except in the terminal stages of heart failure,
`the ventricle operates on an ascending, albeit depressed and flattened,
`function curve (Fig. 232-6), and the augmented ventricular end-dia(cid:173)
`stolic volume and pressure characteristic of heart failure must be
`regarded as helping to maintain the reduced cardiac output, despite
`causing pulmonary and/or systemic venous congestion.
`Congestive heart failure is also characterized by a complex series
`of neurohumoral adjustments. The activation of the adrenergic nervous
`system is discussed on p. 1285; there is also activation of the renin(cid:173)
`angiotensin-aldosterone system and increased release of antidiuretic
`hormone. These influences elevate systemic vascular resistance and en(cid:173)
`hance sodium and water retention and potassium excretion. These ac(cid:173)
`tions are, to a minor extent, opposed by the release of atrial natriuretic
`peptide, which also occurs in congestive heart failure. Patients with se(cid:173)
`vere heart failure may exhibit a reduced capacity to excrete a water load,
`which may result in dilutional hyponatremia. In the presence of heart
`failure, effective filling of the systemic arterial bed is reduced, a condi(cid:173)
`tion that initiates the renal and hormonal changes mentioned above.
`The elevation of systemic venous pressure and the alterations of
`renal and adrenal function characteristic of heart failure vary in their
`relative importance in the production of edema in different patients
`with heart failure. The renin-angiotensin-aldosterone axis is activated
`most intensely by acute heart failure, and its activity tends to decline
`as heart failure becomes chronic. In patients with tricuspid valve
`disease or constrictive pericarditis, the elevated venous pressure and
`the transudation of fluid from systemic capillaries appear to play the
`dominant role in edema formation. On the other hand, severe edema
`may be present in patients with ischemic or hypertensive heart disease,
`in whom systemic venous pressure is within normal limits or is only
`minimally elevated. In such patients, the retention of salt and water
`is probably due primarily to a redistribution of cardiac output and a
`concomitant reduction in renal perfusion, as well as activation of
`the renin-angiotensin-aldosterone axis. Regardless of the mechanisms
`involved in fluid retention, untreated patients with chronic congestive
`heart failure have elevations of total blood volume, interstitial fluid
`volume, and body sodium. These abnormalities diminish after clinical
`compensation has been achieved by treatment.
`
`CLINICAL MANIFESTATIONS OF
`HEART FAILURE
`Dyspnea Respiratory distress that occurs as the result of in(cid:173)
`creased effort in breathing is the most common symptom of heart
`failure (Chap. 32). In early heart failure, dyspnea is observed only
`during activity, when it may simply represent an aggravation of tile
`breathlessness that occurs normally under these circumstances. As
`heart failure advances, however, dyspnea appears with progressively
`less strenuous activity. Ultimately, breathlessness is present even when
`the patient is at rest. The principal difference between exertional
`dyspnea in normal persons and in patients with heart failure is the
`degree of activity necessary to induce the symptom. Cardiac dyspnea
`is observed most frequently in patients with elevations of pulmonary
`venous and capillary pressures. Such patients usually have engorged
`pulmonary vessels and interstitial pulmonary edema, which may be
`evident on radiologic examination. This reduces the compliance of
`the lungs and thereby increases the work of the respiratory muscles
`required to inflate the lungs. The activation of receptors in the lungs
`results in the rapid, shallow breathing characteristic of cardiac dyspnea.
`The oxygen cost of breathing is increased by the excessive work of
`the respiratory muscles. This is coupled with the diminished delivery
`
`Ex. 2007-0426
`
`

`
`1290
`
`PART EIGHT
`Disorders of the Cardiovascular System
`
`of oxygen to these muscles, which occurs as a consequence of the
`reduced cardiac output and which may contribute to fatigue of the
`respiratory muscles and the sensation of shortness of breath.
`Orthopnea Dyspnea in the recumbent position is usually a later
`manifestation of heart failure than exertional dyspnea. Orthopnea oc(cid:173)
`curs because of the redistribution of fluid from the abdomen and
`lower extremities into the chest causing an increase in the pulmonary
`capillary hydrostatic pressure, as well as elevation of the diaphragm
`accompanying supine posture. Patients with orthopnea must elevate
`their heads on several pillows at night and frequently awaken short
`of breath or coughing (the so-called nocturnal cough) if their heads
`slip off the pillows. The sensation of breathlessness usually is relieved
`by sitting upright, since this position reduces venous return and pulmo(cid:173)
`nary capillary pressure, and many patients report that they find relief
`from sitting in front of an open window. In far-advanced heart failure,
`orthopnea may become so severe that patients cannot lie down at all
`and must spend the entire night in a sitting position. On the other hand,
`in other patients with long-standing, severe left ventricular failure,
`symptoms of pulmonary congestion may actually diminish with time
`as the function of the right ventricle becomes impaired.
`Paroxysmal (Nocturnal) Dyspnea This term refers to attacks
`of severe shortness of breath and coughing that generally occur at night,
`usually awaken the patient from sleep, and may be quite frightening.
`Though simple orthopnea may be relieved by sitting upright at the
`side of the bed with legs dependent, in the patient with paroxysmal
`nocturnal dyspnea, coughing and wheezing often persist even in this
`position. The depression of the respiratory center during sleep may
`reduce ventilation sufficiently to lower arterial oxygen tension, particu(cid:173)
`larly in patients with interstitial lung edema and reduced pulmonary
`compliance. Also, ventricular function may be further impaired at night
`because of reduced adrenergic stimulation of myocardial function.
`Cardiac asthma is closely related to paroxysmal nocturnal dyspnea
`and nocturnal cough and is characterized by wheezing secondary to
`bronchospasm-most prominent at night. Acute pulmonary edema
`(Chap. 32) is a severe form of cardiac asthma due to marked elevation
`of pulmonary capillary pressure leading to alveolar edema, associated
`with extreme shortness of breath, rales over the lung fields, and the
`transudation and expectoration of blood-tinged fluid. If not treated
`promptly, acute pulmonary edema may be fatal.
`Cheyne-Stokes Respiration Also known· as periodic or cyclic
`respiration, Cheyne-Stokes respiration is characterized by diminished
`sensitivity of the respiratory center to arterial Pc02• There is an apneic
`phase, during which the arterial P02 falls and the arterial Pc02 rises.
`These changes in the arterial blood stimulate the depressed respiratory
`center, resulting in hyperventilation and hypocapnia, followed in tum
`by recurrence of apnea. Cheyne-Stokes respiration occurs most often
`in patients with cerebral atherosclerosis and other cerebral lesions, but
`the prolongation of the circulation time from the lung to the brain that
`occurs in heart failure, particularly in patients with hypertension and
`coronary artery disease and associated cerebral vascular disease, also
`appears to precipitate this form of breathing.
`Fatigue, Weakness, and Abdominal Symptoms These nonspe(cid:173)
`cific but common symptoms of heart failure are related to the reduction
`of perfusion of skeletal muscle. Exercise capacity is reduced by the
`limited ability of the failing heart to increase its output and deliver
`oxygen to the exercising muscle. Anorexia and nausea associated with
`abdominal pain and fullness are frequent complaints and may be related
`to the congested liver and portal venous system.
`Cerebral Symptoms
`In severe heart failure, particularly in el(cid:173)
`derly patients with accompanying cerebral arteriosclerosis, reduced
`cerebral perfusion, and arterial hypoxemia, there may be alterations in
`the mental state characterized by confusion, difficulty in concentration,
`impairment of memory, headache, insomnia, and anxiety. Nocturia is
`common in heart failute and may contribute to insomnia.
`PHYSICAL FINDINGS (See Chap. 227)
`In moderate heart
`failure, the patient appears to be in no distress at rest except that he
`
`or she may be uncomfortable when lying flat for more than a
`minutes. In more severe heart failure, the pulse pressure
`diminished, reflecting a reduction in stroke volume, and oc(:aston~
`the diastolic arterial pressure is elevated as a consequence of
`ized vasoconstriction. In acute heart failure, hypotension may
`inent. There may be cyanosis of the lips and nail beds and
`tachycardia, and the patient may insist on sitting upright
`venous pressure is often abnormally elevated in heart failure
`be recognized by observing the extent of distention of
`veins. In the early stages of heart failure, the venous pressure
`be normal at rest but may become abnormally elevated
`immediately after exertion as well as with sustained pressure
`abdomen (positive abdominojugular reflux).
`Third and fourth heart sounds are often audible but are not
`for heart failure, and pulsus altemans, i.e., a regular rhythm in
`there is alternation of strong and weak cardiac contractions and
`fore alternation in the strength of the peripheral pulses, may be
`Pulsus alternans, a sign of severe heart failure, may be
`sphygmomanometry and in more severe instances by
`frequently follows an extrasystole and is observed most COinrrtonl
`patients with cardiomyopathy or hypertensive or ischemic
`disease.
`Pulmonary Rales Moist, inspiratory, crepitant rales and
`to percussion over the lung bases are common in patients with
`failure and elevated pulmonary venous and capillary pressure8:
`patients with pulmonary edema, rales may be heard widely over
`lung fields; they are frequently coarse and sibilant and may be
`panied by expiratory wheezing. Rales may, however, be
`many conditions other than left ventricular failure. Some
`with long-standing heart failure have no rales because of
`lymphatic drainage of alveolar fluid.
`Cardiac Edema (See Chap. 37) This is usually aep•endlent.,:CQ
`curring in the legs symmetrically, particularly in the pretibial
`and ankles in ambulatory patients, in whom it is most pnnnime11t
`the evening, and in the sacral region of individuals at bed rest.
`edema of the arms and face occurs rarely and then only late in
`course of heart failure.
`Hydrothorax and Ascites Pleural effusion in congestive
`failure results from the elevation of pleural capillary pressure.
`transudation of fluid into the pleural cavities. Since the pleural
`drain into both the systemic and pulmonary veins, hydrothorax
`most commonly with marked elevation of pressure in both
`systems but also may be seen with marked elevation of pressure
`either venous bed. It is more frequent in the right pleural cavity
`in the left. Ascites also occurs as a consequence of transudation
`results from increased pressure in the hepatic veins and the
`draining the peritoneum (Chap. 46). Marked ascites occurs ·
`frequently in patients with tricuspid valve disease and rnr1otrtctrve
`pericarditis.
`Congestive Hepatomegaly An enlarged, tender, pulsating
`also accompanies systemic venous hypertension and is observed
`only in the same conditions in which ascites occurs but also in
`forms of heart failure from any cause. With prolonged, severe hepat(}l(cid:173)
`megaly, as in patients with tricuspid valve disease or chronic constric•
`tive pericarditis, enlargement of the spleen, i.e., congestive splenomeg(cid:173)
`·
`aly, also may occur.
`Jaundice This is a late finding in congestive heart failure arid
`is associated with elevations of both the direct- and indirect-reacting
`bilirubin; it results from impairment of hepatic function secondary. to
`hepatic congestion and the hepatocellular hypoxia associated with
`central lobular atrophy. Serum transaminase concentrations are fte;.
`quently elevated. If hepatic congestion occurs acutely, the jaundice
`may be severe and the enzymes strikingly elevated.
`.
`Cardiac Cachexia With severe chronic heart failure there may
`be serious weight loss and cachexia because of (1) elevation of circulat(cid:173)
`ing concentrations of tumor necrosis factor; (2) elevation of the meta(cid:173)
`bolic rate, which results in part from the extra work performed by the
`respiratory muscles, the increased oxygen needs of the hypertrophied
`heart, and/or the discomfort associated with severe heart failure; (~}
`
`Ex. 2007-0427
`
`

`
`nausea, and vorrutmg due to central causes, to digitalis
`or to congestive hepatomegaly and abdominal fullness;
`of intestinal absorption due to congestion of the intesti-
`and (5) rarely, in patients with particularly severe failure
`side of the heart, protein-losing enteropathy.
`:Manifestations With reduction of blood flow, the extrem(cid:173)
`be cold, pale, and diaphoretic. Urine flow is depressed, and
`contains albumin and has a high specific gravity and a
`:enuauvu of sodium. In addition, prerenal azotemia may be
`·patients with long-standing severe heart failure, impotence
`are common.
`
`In addition to the en(cid:173)
`FINDINGS
`particular chambers characteristic of the lesion respon(cid:173)
`failure, distention of pulmonary veins and redistribution
`is common in patients with heart failure and elevated
`vascular pressures. Also, pleural effusions may be evident
`with interlobar effusions.
`DIAGNOSIS The diagnosis of conge!)tive
`failure may be established by observing some combination of
`manifestations of heart failure described above, together
`findings characteristic of one of the etiologic forms of heart
`Table 233-1 shows the Framingham criteria, which are useful
`diagnosis of heart failure. Since chronic heart failure is often
`with cardiac enlargement, the diagnosis should be ques(cid:173)
`but is by no means excluded, when all chambers are normal
`Two-dimensional echocardiography is particularly useful in
`the dimensions of each cardiac chamber. Heart failure may
`to distinguish from pulmonary disease, and the differential
`is discussed in Chap. 32. Pulmonary embolism also presents
`of the manifestations of heart failure, but hemoptysis, pleuritic
`pain, a right ventricular lift, and the characteristic mismatch
`ventilation and perfusion on lung scan should point to this
`(see Chap. 261).
`edema may be due to varicose veins, cyclic edema, or
`v•u•uvnru effects (Chap. 37), but in these patients there is no jugular
`hypertension at rest or with pressure over the abdomen. Edema
`to renal disease can usually be recognized by appropriate
`function tests and urinalysis and is rarely associated with eleva(cid:173)
`of venous pressure. Enlargement of the liver and ascites occur in
`with hepatic cirrhosis and also may be distinguished from
`failure by normal jugular venous pressure and absence of a
`abdominojugular reflux.
`
`CHAPTER 233
`Heart Failure
`
`1291
`
`f3c: TREATMENT
`The treatment of heart failure may be divided logically into three
`components: (1) removal of the precipitating cause, (2) correction
`of the underlying cause, and (3) control of the congestive heart
`failure state. The first two are discussed in other chapters together
`with each specific disease entity or complication. An example is
`the treatment of pneumococcal pneumonia and acute heart failure
`(removal of the precipitating cause) followed by mitral valvotomy
`(correction of the underlying cause) in a patient with mitral stenosis.
`In many instances, surgical treatment will correct or at least alleviate
`the underlying cause. The third component of the treatment of heart
`failure, i.e., control of the congestive heart failure state, may, in
`tum, be divided into three categories: (l) reduction of cardiac work
`load, including both the preload and the afterload; (2) control of
`excessive retention of salt and water; and (3) enhancement of myo(cid:173)
`cardial contractility. The vigor with which each of these measures
`is pursued in any individual patient should depend on the severity
`of heart failure. Following effective treatment, recurrence of the
`clinical manifestations of heart failure can often be prevented by
`continuing those meas.ures that were originally effective.
`While a simple rule for the treatment of all patients with heart
`failure cannot be formulated because of the varied etiologies, hemo(cid:173)
`dynamic features, clinical manifestations, and severity of heart fail(cid:173)
`ure, insofar as the treatment of chronic congestive failure is con(cid:173)
`cerned, the administration of an angiotensin-converting enzyme
`inhibitor (e.g., lisinopril 10 mg q.d.) has been shown to retard the
`development of heart failure and should be begun early in patients
`with cardiac dilatation and/or hypertrophy, even if they are asymp(cid:173)
`tomatic. Then, as symptoms develop, simple measures such as mod(cid:173)
`erate restriction of activity and sodium intake should be tried (Fig.
`233-1 ). If these and the ACE inhibitor are insufficient, therapy with
`a combination of a diuretic, a vasodilator, and usually a digitalis
`glycoside is then begun. The next step is more rigorous restriction
`of salt intake and higher doses of loop diuretics, sometimes accom(cid:173)
`panied by other diuretics. If heart failure persists, hospitalization
`with rigid salt restriction, bed rest, intravenous vasodilators, and
`positive inotropic agents comes next. In some patients, the order in
`which these measures are applied may be altered.
`
`Criteria for Diagnosis of Congestive Heart Failnre*
`
`New York Heart Association functional class
`I
`II
`Ill
`IV
`
`Restricted Na• intake
`
`Restricted physical activity
`
`Digoxin
`
`Diuretics
`
`reduced by one-third from normal
`acny~cardlia (""' 120 bpm)
`
`IV inotropic agents
`(sympathomimetic drugs)
`and vasodilators
`Special measures
`(intra-aortic balloon pump, -L---.1..-------'-----'----'--'-....-J
`cardiac transplant)
`
`a clinical diagnosis of congestive heart failure by these criteria, at least
`major and two minor criteria are required.
`KKL Ho et al, Circulation 88:107, 1993.
`
`FIGURE 233-1 Overview of the treatment of heart failure. [From RA Kelly,
`TW Smith: Treatment of stable heart failure: Digitalis and diuretics, in Heart
`Failure: Cardiac Function and Dysfunction, in WS Colucci ( ed), Atlas of Heart
`Diseases, vol4, EBraunwald(seriesed), Philadelphia, Current Medicine, 1995.]
`
`Ex. 2007-0428
`
`

`
`1360
`
`PART EIGHT
`Disorders of the Cardiovascular System
`
`COMPLICATIONS OF MYOCARDIAL
`INFARCTION AND THEIR TREATMENT
`
`VENTRICULAR DYSFUNCTION Following myocardial in(cid:173)
`farction, the left ventricle undergoes a series of changes in shape, size,
`and thickness in both the infarcted and noninfarcted segments. This
`process is referred to as ventricular remodeling and generally precedes
`the development of clinically evident congestive heart failure in the
`months to years after infarction. Soon after myocardial infarction, the
`left ventricle begins to dilate. Acutely, this results from expansion of
`the infarct (i.e., slippage of muscle bundles, disruption of normal
`myocardial cells, and tissue loss within the necrotic zone, resulting
`in disproportionate thinning and elongation of the infarct zone). Later,
`lengthening of the noninfarcted segments occurs as well. The overall
`chamber enlargement that occurs is related to the size and location of
`the infarct, with greater dilation following infarction of the apex of
`the left ventricle and causing more marked hemodynamic impairment,
`more frequent heart failure, and a poorer prognosis. Progressive dila(cid:173)
`tion and its clinical consequences may be ameliorated by therapy with
`ACE inhibitors and other vasodilators (e.g., nitrates) (Fig. 243-2).
`Thus, in patients with a lowered ejection fraction (less than 40 percent),
`regardless of whether or not heart failure is present, ACE inhibitors
`should be prescribed.
`HEMODYNAMIC ASSESSMENT Pump failure is now the
`primary cause of in-hospital death from acute myocardial infarction.
`The extent of ischemic necrosis correlates well with the degree of pump
`failure and with mortality, both early (within 10 days of infarction) and
`later. The most common clinical signs are pulmonary rales and S3 and
`S4 gallop rhythms. Pulmonary congestion is also frequently seen on
`the chest roentgenogram. Elevation of left ventricular filling pressure
`and pulmonary artery pressure are the characteristic hemodynamic
`findings, but it should be appreciated that these findings may result
`from a reduction of ventricular compliance (diastolic failure) and/or
`a reduction of stroke volume with secondary cardiac dilation (systolic
`failure) (Chap. 232).
`A classification originally proposed by Killip divides patients into
`four groups: class I, no signs of pulmonary or venous congestion;
`class II, moderate heart failure as evidenced by rales at the lung bases,
`S3 gallop, tachypnea, or signs of failure of the right side of the heart,
`including venous and hepatic congestion; class III, severe heart failure,
`pulmonary edema; and class IV, shock with systolic pressure less than
`90 mmHg and evidence of peripheral vasoconstriction, peripheral
`cyanosis, mental confusion, and oliguria. The expected hospital mortal(cid:173)
`ity rate of patients in these clinical classes when this classification
`was established in 1967 was as follows: class I, 0 to 5 percent;
`class II, 10 to 20 percent; class III, 35 to 45 percent; and class
`IV, 85 to 95 percent. With advances in management, the mortality
`rate has fallen, perhaps by as much as one-third to one-half, in each
`class.
`Hemodynamic evidence of abnormal left ventricular function ap(cid:173)
`pears when contraction is seriously impaired in 20 to 25 percent of
`the left ventricle. Infarction of 40 percent or more of the left ventricle
`usually results in cardiogenic shock (see below). Positioning of a
`balloon flotation catheter in the pulmonary artery permits monitoring
`of left ventricular filling pressure; this technique is useful in patients
`who exhibit hypotension and/or clinical evidence of heart failure.
`Cardiac output can also be determined with a pulmonary artery cathe(cid:173)
`ter. With the addition of intraarterial pressure monitoring, systemic
`vascular resistance can be calculated as a guide to adjusting vasopressor
`and vasodilator therapy. Some patients with acute myocardial in(cid:173)
`farction have markedly elevated left ventricular filling pressures (>22
`mmHg) and normal cardiac indexes [>2.6 and >3.6 Ll(minlm2)],
`while others have relatively low filling pressures ( < 15 mmHg) and
`reduced cardiac indexes. The former patients usually benefit from
`diuresis, while the latter may respond to volume expansion by means
`of intravenous administration of colloid-containing solutions.
`
`Hypovolemia This is an easily corrected condition that may
`contribute to the hypotension and vascular collapse associated with
`myocardial infarction in some patients. Hypovolemia may be second(cid:173)
`ary to previous diuretic use, to reduced fluid intake during the early
`stages of the illness, and/or to vomiting associated with pain or medica(cid:173)
`tions. Consequently, hypovolemia should be identified and corrected
`in patients with acute myocardial infarction and hypotension before
`more vigorous forms of therapy are embarked on. Central venous
`pressure reflects right rather than left ventricular filling pressure and
`is an inadequate guide for adjustment of blood volume, since left
`ventricular function is almost always affected much more adversely
`than right ventricular function in acute myocardial infarction. The
`optimal left ventricular filling or pulmonary artery wedge pressure
`may vary considerably among patients. Each patient's ideal level
`(generally approximately 20 mmHg) is reached by cautious fluid
`administration during careful monitoring of oxygenation and cardiao
`output. Eventually, the cardiac output plateaus and further increases
`in left ventricular filling pressure only increase congestive symp.
`toms and decrease systemic oxygenation without raising
`·
`pressure.
`lk TREATMENT
`The management of heart failure in association with
`infarction is similar to that of acute heart failure secondary to
`forms of heart disease (avoidance of hypoxemia, diuresis,
`reduction, inotropic support) (Chap. 233), except that the
`of digitalis administration in acute myocardial infarction are
`pressive. On the other hand, diuretic agents are extremely aHoot: .. _,,
`as they diminish pulmonary congestion in the presence of
`and/or diastolic heart failure. A fall in left ventricular filling
`and an improvement in orthopnea and dyspnea follow the ·
`administration of furosemide. This drug should be used with
`however, as it can result in a massive diuresis with associated
`crease in plasma volume, cardiac output, systemic blood
`and hence coronary perfusion. Nitrates in various forms may.
`used to decrease preload and congestive symptoms. Oral ·
`dinitrate, topical nitroglycerin ointment, or intravenous
`··
`' · .._'
`all have the advantage over a diuretic of lowering preload
`venodilation without decreasing the total plasma volume. In
`nitrates may improve ventricular compliance if ischemia is
`as ischemia causes an elevation of left ventricular filling
`The patient with pulmonary edema is treated as described in
`233, but vasodilators must be used with caution to prevent
`hypotension. As noted earlier, ACE inhibitors are an ideal clas
`drugs for management of ventricular dysfunction following
`dial infarction, especially for the long term.
`
`CARDIOGENIC SHOCK
`In recent years, efforts to
`infarct size and prompt treatment of ongoing ischemia and other
`plications of myocardial infarction appear to have reduced the
`dence of cardiogenic shock from 20 percent to about 7 percent.
`10 percent of patients with this condition present with it on
`while 90 percent develop it during hospitalization. Typically,
`who develop cardiogenic shock have severe multivessel coronary
`tery disease with evidence of "piecemeal" necrosis extending
`from the original infarct zone.
`It is useful to consider cardiogenic shock as a form of
`left ventricular failure. This syndrome is characterized by
`hypotension with systolic arterial pressure of <80 mmHg and a
`reduction of cardiac index [ < 1.8 Ll(minlm2
`)] in the face of an
`left ventricular filling (pulmonary capillary wedge) pressure
`mmHg). Hypotension alone is not a basis for the diagnosis of
`genic shock, because many patients who make an uneventful
`will have serious hypotension (systolic pressure of <80
`several hours. Such patients often have low left
`pressures, and their hypotension usually resolves with the
`tion of intravenous fluids. In contrast to hypovolemic '-···~nt,on'
`cardiogenic shock is generally associated with a mortality rat
`>70 percent; however, recent efforts to restore perfusion by
`
`Ex. 2007-0429
`
`

`
`AMERICAN ACADEMY OF PEDIATRICS
`Committee on Fetus and Newborn
`
`Use of Inhaled Nitric Oxide
`
`ABSTRACT. Approval of inhaled nitric oxide by the
`US Food and Drug Administration for hypoxic respira(cid:173)
`tory failure of the term and near-term newborn provides
`an important new therapy for this serious condition. This
`statement addresses the conditions under which inhaled
`nitric oxide should be administered to the neonate with
`hypoxic respiratory failure.
`
`ABBREVIATIONS. ECMO, extracorporeal membrane oxygenation;
`iNO, inhaled nitric oxide; FDA, US Food and Drug Administration.
`
`H ypoxic respiratory failure in neonates born at
`
`or near term may be caused by such condi(cid:173)
`tions as primary persistent pulmonary hy(cid:173)
`pertension, respiratory distress syndrome, aspiration
`syndromes, pneumonia or sepsis, and congenital di(cid:173)
`aphragmatic hernia. Conventional therapies, which
`have not been validated by randomized controlled
`trials, include administration of high concentrations
`of oxygen, hyperventilation, high-frequency ventila(cid:173)
`tion, the induction of alkalosis, neuromuscular block(cid:173)
`ade, and sedation.1 Despite aggressive conventional
`therapy, neonatal respiratory failure was associated
`with a high rate of mortality b