Pathogenesis and Management of Acute Heart Failure and Cardiogenic Shock: Role of Inotropic Therapy

Pathogenesis and Jt'anagement of Acute Heart Failure

and Carcllogenlc Shock: Role of Inotropic Therapy* A. lain McGhie, M.D.; and Richard A. Goldstein, M.D.

treatment modalities.

Patients with acute heart failure or cardiogenic shock following myocardial infarction have a high mortality. The first priority is to salvage any remaining viable myocardium, either by thrombolytic agents or, if necessary, by coronary angioplasty. A mechanical cause for the heart failure or shock needs to be excluded. Thereafter, the optimal therapeutic regimen needs to be chosen on the basis of each patient's hemodynamic pro6le. Patients can be broadly classi6ed into three groups: (1) patients with a high left ventricular filling pressure (> 18 mm Hg) and a cardiac index <2.2 UminlmS but systolic arterial pressure > 100 mm Hg, (2) patients with a systolic arterial pressure <90 mm Hg, left ventricular 611ing pressure > 18 mm Hg, and cardiac iDdex <2.2 Uminlml; and (3) patients with an elevated right ventricular 611ing pressure (> 10 mm Hg) and cardiac index <2.2 Uminlml and a systolic arterial pressure <100 mm Hg, Patients in the Brst subset usually require the use of vasodilator therapyand/or dobutamine. The choice of inotropic agent in patients in the second hemodynamic subset depends on the degree of systemic hypotension; dopamine is usually preferred initially because it increases arterial pressure in addition to improving cardiac output. Once the systemic blood pressure has been stabilized, dobutamine can be substituted for superior augmentation of cardiac output and its additional bene6cia1 effects on the left ventricular SlIing pressure. Norepinephrine may be indicated in cases of severe systemic hypotension. Patients in hemodynamic subset 3, ie, right ventricular infarction, are treated with volume ~ion and dobutamine. Use of nonpharmacologic means of circuIatory support, eg, intra-aortic balloon pump or left ventricular assist device may also be required in any of these subsets.

ETIOLOGY OF ACUTE HEART FAILURE

he medical treatment of acute heart failure and T cardiogenic shock has changed dramatically over

the last 10 to 15 years. The advent of bedside hemodynamic monitoring has improved the treatment of such patients and resulted in the greater understanding of the pathophysiologic processes involved. New inotropic agents such as dobutamine and the phosphodiesterase inhibitors, eg, amrinone and milrinone, also became available. The role ofinotropes in combination with other interventions such as vasodilator therapy and intra-aortic balloon counterpulsation have been increasingly appreciated. This article will review the basic pathophysiology of acute heart failure and cardiogenic shock, particularly in the setting of acute myocardial infarction, and discuss the role of inotropic therapy in the context of the hemodynamics and other *From the Cardiology Division, The UDiversity of Texas Medical School at Houston, Houston. 828S

I

The identification of the etiology is crucial for the correct treabnent of a patient with acute heart failure. The most common causes of acute heart failure are listed in Table 1. Acute, massive myocardial infarction as the cause of acute heart failure is usually obvious, being diagnosed by the history associated with indirect evidence of extensive infarction with widespread electrocardiographic abnormalities and considerable elevation of serum enzyme levels. However, it is important to exclude one of the several complications of myocardial infarction that can result in acute heart failure. For example, a not infrequent scenario is a patient with a recent acute myocardial infarction who suddenly has development of acute heart failure associated with the appearance of a systolic murmur. This usually indicates either acute mitral regurgitation, resulting from papillary muscle dysfunction or rupture of part of the mitral valve apparatus; or rupture of the interventricular septum resulting in a ventricular septal defect with a left-to-right shunt. Distinguishing between these two complications is difficult clinically and physical signs cannot be relied on. The use of two-dimensional and Doppler echocardiography usually provides the diagnosis. 1 The presence of a left-to-right shunt can be con6rmed and quantified by right heart catheterization. Both these complications require early operative correction. Rupture of the left ventricular free wall usually results in sudden severe chest pain, hypotension, distention of neck veins, and electromechanical dissociation, with attempts at cardiopulmonary resuscitation being unsuccessful. Occasionally, it may produce a rapidly progressive cardiac tamponade. Table I-Poaible Cauaa of Acute IletJrt Failure or Shock Massive myocardial infarction Acute mitral regurgitation Ventricular septal defect Right ventricular infarction Myocardial infarction with pre-existing left ventricular dysfunction Type 1 aortic dissection Hypovolemia Cardiac rupture or tamponade Arrhythmialheart block Drug related

Acute Heart Failureand Cardiogenic Shock (McGhie, Goldstein)

Acute, profound right ventricular dysfunction can occur in the presence of infarction of the right ventricular free wall. This is usually associated with infarction of the inferior wall of the left ventricle and produces a clinical syndrome termed "right ventricular infarction" that was first described by Cohn et al2 in 1974. The patient is commonly hypotensive and vasoconstricted. Other findings include the presence of clear lung fields on auscultation and chest radiograph combined with an elevated jugular venou,s pressure that increases on inspiration (Kussmaul s sign). Hemodynamics typically consist of elevated right atrial and ventricular diastolic pressures (> 10 mm Hg), with the ratio of right-to-left ventricular filling pressures being approximately 0.8 to 1.0.2-4 It should be remembered that massive pulmonary embolism and cardiac tamponade can produce similar hemodynamic patterns. Extension or sudden expansion of a recent myocardial infarction can result in the sudden development of acute heart failure,S as can a relatively small infarct in a patient with already compromised left ventricular function. The presence of an arrhythmia or high-grade heart block can also result in the sudden development of acute heart failure that can be readily identified from the electrocardiogram. Aortic dissection can present with symptoms similar to acute myocardial infarction and acute heart failure if the intimal tear is in the ascending aortic arch and dissects proximally to involve the aortic annulus resulting in acute aortic regurgitation. The history may give clues, eg, a history of hypertension, sudden deceleration inj~ or Marfan's syndrome; the pain often has a "ripping" quality that radiates through to the back. There may be an early diastolic, decrescendo murmur; however, in this acute scenario, the only sign may be a soft first heart sound due to premature closure of the mitral valve. In addition, the patient may be hypertensive or have unequal pulses if the dissection involves one of the branches of the aorta. Other causes of shock, such as hypovolemia, sepsis, or drug-induced, eg, barbiturates, should be considered but are usually self-evident. PATHOPHYSIOLOGIC CONSIDERATIONS

lbthophysiologic Consequences ofAcute Myocardial Infarction on Left Ventricular Function

Left ventricular dysfunction is relatively common in patients with acute myocardial infarction. The immediate result of myocardial infarction is a reduction in the forward output and the total force of the left ventricle. In addition, a decrease in myocardial compliance has been observed both experimentally and in clinical studies.v" The decrease in compliance is the major contributing factor to the increase in left ventricular end-diastolic pressure (LVEDP), although

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LV Volume FIGURE 1. Effect of compliance on the left ventricular (LV) pressure and volume curves. Point A represents a patient with a pressurevolume curve and normal ventricular compliance; B represents a with patient with an identical ventricular volume that is as~ociated higher ventricular pressure because of reduced compliance.

this may be explained in part by an increase in left ventricular volume." This increase in compliance can produce an elevation of left ventricular filling pressure and pulmonary edema even though the left ventricular end-diastolic volume and total blood volume may be normal (Fig 1). Volume is redistributed from the central circulation into the alveoli. The onset of pulmonary edema usually occurs very rapidly following an elevation of LVEDP above 18 mm Hg (Fig 2) despite the fact that left ventricular volume may not be increased. The stroke volume has the ability to increase by approximately 20 percent by increasing myocardial contractility'? However, beyond a critical infarct size, between 20 and 25 percent of the left ventricle, forward output has to be maintained by increasing myocardial fiber length. 11 The increase in end-diastolic volume can be achieved by two mechanisms, either (1) ventricular distention, ie, an increase in enddiastolic pressure, and/or (2) ventricular dilatation, te, a rightward shift of the pressure/volume curve. The former mechanism is more likely to be prominent

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LV Filling Pr••sur. FIGURE 2. Effect of a sudden elevation in left ventricular (LV) filling pressure on the water content of the lung.

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during the acute phase of myocardial infarction while the latter compensatory mechanism is more likely to be important in the chronic phase in the months following myocardial infarction. I! Cardiogenic shock usually develops in patients who have more than 40 percent of their myocardial mass irreversibly damaged. 13

coronary flow and will increase myocardial O2 requirements despite improving systemic arterial pressure (Fig 3). Similarly a drug that increases cardiac output but also increases myocardial O2 demand greater than supply may be detrimental; corresponding, a drug used to induce excessive venodilation could decrease myocardial perfusion despite lowering preload.

Myocardial Oxygen Supply and Demand

Goals of Inotropic Agents

To minimize the extent of myocardial necrosis and maximize function in noninfarcted myocardium, another important consideration in treating patients with acute myocardial infarction complicated by pump failure is the balance between myocardial oxygen supply and demand. Myocardial perfusion depends on (1) the pressure gradient between the coronary arterial system and left ventricular pressures, and (2) the duration of diastole when the majority of coronary flow occurs because of compression of epicardial vessels during systole. Therefore, myocardial perfusion, at a given heart rate, can be increased by either raising the arterial diastolic pressure or by lowering the LVEDl! At the bedside, perfusion pressure can be approximated as the difference between diastolic arterial pressure and pulmonary capillary wedge pressure. Attention to the heart rate is also important since tachycardia will adversely affect myocardial perfusion by shortening the length of diastole. Another compounding factor in patients with multivessel coronary disease is the limited coronary flow reserve to myocardium subtended by diseased vessels, which prevents increases in demand being accompanied by commensurate increases in flow: 14 Therefore, it is obvious that pharmacologic interventions aimed at improving ventricular performance have to be used judiciously For example, an intervention that nonselectively increases both diastolic arterial pressure and pulmonary capillary wedge pressure will not improve

The goals of inotropic therapy in acute heart failure and cardiogenic shock are to increase cardiac output by increasing myocardial contractility without increasing myocardial O2 demands in order to provide adequate systemic perfusion. Specific inotropic agents often have additional hemodynamic effects that may be either detrimental or beneficial depending on the individual's specific requirements at any particular point in time.

LVFP

(mm Hg)

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Clinical Evaluation

Acute heart failure results in symptoms of acute onset dyspnea and respiratory distress, often associated with expectoration of white or pink frothy sputum. The skin is cool, clammy, and diaphoretic; the heart rate and blood pressure are also elevated indicative of sympathetic hyperactivity There is often a third heart sound or summation, gallop rhythm, and basilar fine rales present. If the cardiac output is markedly decreased, then additional features indicative of shock are also present, ie, hypotension, oliguria, and obtundation are also present. However, clinical evaluation of the hemodynamic status of patients with acute heart failure is insensitive and may not provide the information necessary to treat these patients optimally In addition, clinical findings can be misleading if the physician is not aware of their limitations, for example, reliance on the presence of rales as an indirect indicator of volume status. Pulmonary edema occurs rapidly after elevation

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Dia.tollc Art.,lal Pr••sur. (mm Hg FIGURE 3. Effect of different left ventricular filling pressures (LVFP) on the relationship between coronary flow and diastolic arterial pressure; see text for further details. 828S

AsSESSMENT OF HEMODYNAMIC STATUS

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FIGURE 4. Delayed clearance of water from lungs resulting in the "phase lag" between the left ventricular &lling pressure and clinical or radiologic findings; see text for further details. Acute Heart Fa11ur8 and C8rdiogenic Shock (McGhie, Goldstein)

of LVEDP (Fig 2). However, clearance of pulmonary edema from the lungs following correction of the LVEDP may take several days. Thisdelay in resorption of fluid from the third space back into the intravascular space is often referred to as the "phase lag" (Fig 4). During this period, the presence of rales and/or radiologic evidence of pulmonary edema may not reflect the current prevailing left ventricular pressures. This could lead to inappropriate use ofdiuretics on the false assumption that the patient is volume overloaded and could result in detrimental effects on the intravascular volume and left ventricular filling pressure causing a further decrease in cardiac output. Hemodynamic EvalfUltion

The use of balloon flotation right heart catheters to monitor central hemodynamics is pivotal in the treatment of patients with acute heart failure and cardiagenic shock. It allows the measurement of right atrial, pulmonary artery, and pulmonary wedge pressure as well as measurement of the cardiac output. Measurement of the intra-arterial pressure is also strongly advised in the presence ofsevere hypotension (systolic <80 mm Hg) or cardiogenic shock or in patients receiving inotropic or vasodilating agents. Accurate characterization of the hemodynamic abnormalities allows the appropriate selection of pharmacologic agents and also the monitoring of their effects to maximize the cardiac output at the lowest optimal wedge pressure. Patients with pump failure can be broadly classified into three subsets according to their hemodynamics.w" (1) patients with a high left ventricular filling pressure (> 18 mm Hg) and low cardiac index <2.2 Umin/m2 but with a systolic arterial pressure > 100 mm Hg, (2) patients with systolic arterial pressure <90 mm Hg and an elevated left ventricular filling pressure > 18 mm Hg and reduced cardiac index <2.2 Umin/m2; and (3) patients with elevated right atrial and right ventricular diastolic pressures (> 10 mm Hg), cardiac index <2.2 Uminl m2, and systolic arterial pressure <100 mm Hg suggestive of underlying right ventricular infarction. SYMPATHOMIMETIC INOTROPIC AGENTS

The sympathomimetic inotropic class of drugs include both the naturally occurring amines, eg, dopamine, norepinephrine, and epinephrine, and the synthetic amines, eg, dobutamine and isoproterenol. They all produce their effects by specifically stimulating one or a combination of specific adrenergic receptors; the cardiac effects of inotropy and chronotropy are mediated via the PI-adrenergic receptors, while the peripheral vascular effects are produced by either stimulation of the (I.-receptors resulting in vasoconstriction, or the P2-receptors resulting in vasodilation. In addition, they .all share similar pharmacokinetics that have

characteristics that make them very suitable for use in the acute and often rapidly changing circumstances of acute heart failure or cardiogenic shock. They are all administered by a continuous intravenous infusion with an onset of action of <5 min with a peak effect after approximately 15 min. Their half-life is approximately 1.5 to 2.5 min, and excretion is by hepatic metabolism and renal excretion. These attributes allow these agents to be rapidly titrated to the individual patient's specific requirements at any particular time.

Norepinephrine Norepinephrine, a naturally occurring adrenergic neurotransmitter, stimulates the vascular ai-receptors resulting in vasoconstriction and an increase in arterial blood pressure and the cardiac PI-receptors causing positive inotropy and ehronotropy Norepinephrine is a very powerful pressor agent, with much less overall positive chronotropic effect than either dopamine or dobutamine. It has a limited role, used for its vasopressor effect in treatment of cardiogenic shock in a severely hypotensive patient «70 mm Hg) with a normal or reduced systemic vascular reststance.P Small doses of norepinephrine can be given to obtain a systemic arterial pressure without the side effects, in particular the arrhythmogenic effect, associated with pressor doses of dopamine. The usual starting dose is 1 to 4 fl-Wmin titrated to provide the optimal clinical and hemodynamic effect.

Dopamine

This is the precursor of norepinephrine and epinephrine and exerts its effects by direct stimulation of (I., P, and dopaminergic receptors; and indirectly by causing release of norepinephrine from the presynaptic sympathetic nerve terminals. 19 ,JO In low doses (2 to 5 fl-w1e,ymin), dopamine stimulates the dopaminergic receptors to dilated and splanchnic blood vessels. Glomerular filtration rate and sodium excretion are increased. Doses in the range of 5 to 10 p,g/kw'min stimulate PI-receptOrs and norepinephrine release from sympathetic nerve terminals resulting in positive inotropic and chronotropic effects. At higher doses (10 to 20 fl-w1e,ymin) (II-receptors are stimulated resulting in peripheral vasoconstriction. Adverse effects of dopamine include sinus tachycardia, tachyarrhythmias, excessive peripheral vasoconstriction, nausea, and vomiting due to stimulation of central dopaminergic receptors and local tissue necrosis (especially if extravasation occurs). Dobutamine Dobutamine is a synthetic catecholamine that increases myocardial contractility by stimulating cardiac PI-receptOrs. In addition, it causes peripheral vasodilation due to P2-receptor stimulation with minimal aCHEST I 102 I 5 I NOVEMBER, 1882 I SUppIen..a 2

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adrenergic effects at higher .doses, accounting for its lack of vasoconstrictor dfect even at high doses," Dobutamine does not cause release of endogenous catecholamines and has no direct renal effects. Dobutamine also appears to have a favorable dfect on diastolic function increasing left ventricular compliance, causing a rightward shift of the pressure-volume curve resulting in both lower myocardial Os requirements and an increase in subendocardial perfusion." In patients with acute myocardial infarction and heart failure, the net hemodynamic effects of dobutamine are as follows: (1) an increase in cardiac output; (2) a decrease in pulmonary capillary wedge pressure; and (3) a decrease in systemic vascular resistance with~t a significant increase in the heart rate. In comparison to dopamine, dobutamine produces smaller rises in heart rate, a lower incidence of arrhythmias, less peripheral vasoconstriction, and a more consistent reduction in the left ventricular 6lling pressure for a comparable rise in the cardiac output. 513,J4 The magnitude of the changes observed with dobutamine alone are similar to the combination of dopamine and nitroprusside.- This usually makes dobutamine the inotrope of choice in most situations; however, its relative lack of vasopressor effect makes its use as a sole agent in a severely hypotensive patient inappropriate. There is a theoretical basis in favor of a combination ofdopamine and dobutamine, although there are relatively few data available on the simultaneous use of the two drugs in cardiogenic shock. As with the other sympathomimetic agents, dobutamine should be started at a low dose, 2 to 5 p,gI1cgI min, increased to provide the required response under close clinical, hemodynamic and electrocardiographic monitoring. Possible adverse effects of dobutamine include an excessive increase in heart rate, development of taehyarrhythmias, and provocation ofmyocardial ischemia may be precipitated." DIGITALIS GLYCOSIDES

The digitalis g1ycosides have long been used as inotropic agents, with several substances being derived from such plants as foxglove and strophanthus, However, today their role in the treatment of acute heart failure or cardiogenic shock is limited. The inotropic action of digoxin is due to its dfects on the Na-K ATPase pump. This results in an increase in intracellular sodium which is associated with an increased calcium concentration increasing the availability of calcium for the contractile proteins. Digoxin increases cardiac output by approximately 7 to 15 percent, without a predictable effect on either systemic vascular resistance or left: ventricular filling pressure.- The onset of action of digoxiIis effects takes 90 min after an intravenous loading dose, and peak effect occurs at 2 to 6 h. The half-life ofdigoxin 36 h. Thus, the effects I30S

of digoxin are modest and unpredictable, and its

pharmacokinetics prevent the dosage from being titrated for a specific hemodynamic effect. Therefore, its principal use in acute heart failure or cardiogenic shock may be to control the ventricular response to atrial fibrillation. PHOSPHODIESTERASE INHIBITORS

All drugs in the class, eg, amrinone and milrinone, increase contractility by inhibiting the cAMP-specific (type III) phosphodiesterase activity; this indirectly increases cAMP levels which, in turn, increases contractili~ rt Amrinone is given as a loading dose of o. 75 mglkg followed by an infusion of5 to 10 Jl-g/kw'min. It cannot be mixed in dextrose, which causes it to precipitate. The drugs onset of action occurs within minutes, and its peak effect is within 10 to 15 min. It has a half-life of 3 to 6 h. In addition, it has a vasodilator action resulting in it having a similar hemodynamic dfect as dobutamine with an increase in cardiac output and a fall in the left:ventricular filling pressure and systemic vascular resistance. 1S Other potential benefits may be minimal chronotropic and arrhythmogenic effects, and this does not increase myocardial oxygen demand. 19 •30 It may be associated with thrombocytopenia (2.4 percent of patients), particularly if therapy is continued beyond 48 h. This effect reverses as the dose is lowered or discontinued. There are limited data available on its use in acute heart failure and its use in this setting is still not clear. CHOICE OF INOTROPIC AGENT

In choosing the appropriate therapeutic regimen, it is helpful to classify patients into the hemodynamic subsets described earlier, ltJtients With a High Left lintncular Filling Emsure (> 18 mm Hg) and Lsna Carditlc Index <2.2 Uminlm' but With a Systolic Arterial f\'8s8Ure >100 mm Hg These patients are best treated initially by using a vasodilator and/or dobutamine. Nitroprusside has a balanced arteriolar and venous dfect, whereas nitroglycerin is predominantly a venodilator. Dobutamine will increase stroke volume and decrease preload and afterload. It is initially started at a dose of 5 Jl-g/kw' min increasing to a maximum of 15 fJ-g/kw'min. 31 Intravenous amrinone with its vasodilating and inotropic effects has effects similar to dobutamine and can also be used in this situation.

lbtients With Systolic Arterial Pmssure <90 mm Hg Elevated uft lintncular Filling f\'8ssure >18 mm Hg and Reduced Cardiac Index <.2..2 Uminlm'and an

These patients constitute a group with only a 20 percent chance of survival. A patient with this hemodynamic profile should be seriously considered for

counterpulsation using an intra-aortic balloon pump. The choice of inotropic agent depends on the degree of hypotension. In this situation, dopamine may be preferred by virtue of the fact that it usually increases arterial pressure together with cardiac output although the increase in cardiac output is usually less than that obtained by dobutamfne.P If the patient's arterial pressure can be stabilized with dopamine, then dobutamine should be added to the regimen and the dopamine dose reduced. However, it should be remembered that with dobutamine, the net peripheral effect is mild vasodilation, which causes a reduction in peripheral resistance and diastolic arterial pressure, and therefore it is not the drug of first choice in the severely hypotensive patient.33 If the pressure is between 70 and 90 mm Hg, dopamine should be used from the beginning, starting with a dose of 5 p,WkW min increasing to 15 p,Wkwmin. Using dopamine at infusion rates >20 p,g/kw'min to increase arterial blood. pressure by its a-adrenergic effect will be associated with a major chronotropic effect and therefore norepinephrine, which has less chronotropic effect, would be preferred." However, norepinephrine can have deleterious effects on regional perfusion to the renal, mesenteric, and skeletal arterial beds and should be used only to maintain cerebral and myocardial perfusion and should be substituted for one of the other inotropic agents as soon as possible.

lbtients With an Elevated Right Atrial and Right lmtricular Diastolic Pressures (> 10 mm Hg), Cardiac Index <2.2 Umin/m2 , and Systolic Arterial ~88U~ <100 mm Hg It is important to identify these patients with right ventricular infarction because they have very sensitive volume depletion often responding to volume infusion. It is particularly important to avoid use of diuretics in these patients. There may be associated left ventricular dysfunction depending on the extent of left ventricular infarction. The right ventricular filling pressure must be increased by rapid infusion of fluid until systemic pressure is stabilized. If this is unsuccessful, inotropic support is required and best results are achieved with dobutamine." Unlike dopamine, dobutamine does not cause pulmonary vasoconstriction that results in an increase in right ventricular afterload. However, if volume replacement and inotropic support are not inadequate, then intra-aortic balloon counterpulsation should be employed. NONPHARMACOLOGIC INTERVENTION

The role of nonpharmacologic intervention should always be considered in this group of patients. As eluded to above, intraaortic balloon counterpulsation has an important role to play in treating these patients;36 the more recent development of left ventrie-

ular assist devices may also be ofuse.:t1 In addition, a marked improvement in survival, in the region of 50 percent, has been reported in patients with cardiogenic shock who underwent percutaneous transluminal coronary angioplasty (PTCA) within the first 18 h following the onset of symptoms. 38 Cardiac transplantation may also have a part to play in a patient who is left with severe irreversible ventricular'dysfunction requiring inotropic support. CONCLUSIONS

Mortality from myocardial infarction has improved in the last decade with the introduction of new therapeutic strategies, in particular the widespread use of thrombolytic agents and the increasing use of p-adrenergic blockade. However) the most common cause of in-hospital mortality still remains pump failure and cardiac rupture. Patients with acute heart failure or cardiogenic shock have a poor prognosis that has not changed in the last decade. 38 Initial treatment in these patients must be to limit the extent of myocardial infarction by reperfusion of the infarctrelated coronary artery by thrombolysis and if unsucOnce loss of contraccessful by coronary angiop1as~ tile myocardium occurs, a complex chain of events is initiated, many of which are often detrimental and result in a vicious cycle producing an inexorable decline in cardiac function. Treatment ofthese patients requires careful clinical and hemodynamic evaluation to exclude any underlying, potentially remediable cause of heart failure or cardiogenic shock. Thereafter) therapy should be guided by the patients prevailing hemodynamic status with the judicious use of inotropic agents and/or vasodilators and diuretics if required. The therapeutic regimen may have to be altered to suit a change in the patient's hemodynamic status. It is critical to understand the effects of pharmacologic agents and to have a clear idea of the goals of such therapies. One also has to be cognizant of how each of the various hemodynamic variables interacts with one another to produce an optimal hemodynamic effect. The appropriate use of inotropic agents provides the clinician with an important pharmacologic tool in the treatment of the patient with acute heart failure or cardiogenic shock following myocardial failure. REFERENCES ·1 Richards n, Hoekenga DE, Leach JIe, et ale Doppler cardiographic diagnosis of interventricular rupture. Chest 1979; 76:101-03 2 Cohn IN, Guilia NH, Broder MI, et a1. Right ventricular infarction. Am J CardioII974; 33:209-14 3 Baigrie RS, Haq A, Morgan CD, et ale The spectrum of right ventricular involvement in inferior wall myocardial infarction: a . clinical,hemodynamic and non-invasive stud~ JAm Coli Cardiol

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