Ventricular Failure and Myocardial Infarction

CHAPTER 40  VENTRICULAR FAILURE AND MYOCARDIAL INFARCTION Maggie C. Machen,

DVM  •  Meg

Sleeper,

VMD, DACVIM (Cardiology)

KEY POINTS • Left ventricular failure can lead to decreased cardiac output and pulmonary edema and in many cases will be associated with arrhythmias. • The primary aims of managing ventricular failure are to support contractility, relieve signs of congestion and suppress arrhythmias. • Myocardial infarction is a rare occurrence in canine and feline patients.

BOX 40-1 

Examples of Common Causes of Ventricular Failure

Primary

• Left ventricular failure: dilated cardiomyopathy (DCM) • Right ventricular failure: arrhythmogenic right ventricular cardiomyopathy (ARVC)

Secondary to Other Cardiac Disease

• Advanced degenerative valve disease with systolic dysfunction • Tachycardia-induced cardiomyopathy BASIC TERMINOLOGY The basic terminology of ventricular failure and myocardial infarction is summarized in the following list: Heart failure: The pathophysiologic state in which the heart is unable to pump sufficient blood to meet the metabolic demands of the tissue while maintaining normal arterial and venous pressures. Systolic heart failure: A defect in the pumping or contractile function of the heart. Diastolic heart failure: A defect in the filling or relaxation function of the heart. Congestive heart failure: The clinical syndrome that results when abnormal cardiac function causes accumulation and retention of fluid, resulting in signs of congestion and edema. Forward heart failure: Decreased cardiac output results in inadequate delivery of blood to the arterial system, leading to diminished organ and muscle perfusion. As a result of reduced renal perfusion, plasma volume and extracellular fluid accumulate, leading to congestion of organs and tissues.1 One example of a cause of forward failure is dilated cardiomyopathy. Backward heart failure: Elevated filling pressure causes increased pressure within the left atrium and the pulmonary vasculature draining into the left atrium. This results in elevated capillary hydrostatic pressure, transudation of fluid into the interstitium, and pulmonary edema. If right-sided heart disease is present and right atrial pressure is increased, the same process can lead to elevated systemic venous pressure and ultimately ascites and subcutaneous edema.1 One example of a cause of backward failure is degenerative valve disease. Circulatory failure: When the delivery of oxygenated blood is insufficient to meet the metabolic demands of the body tissue.

CAUSES OF VENTRICULAR (SYSTOLIC) FAILURE Primary Causes Ventricular failure can be primary in origin, most commonly caused by dilated cardiomyopathy (DCM) affecting the left ventricle (LV) or by arrhythmogenic right ventricular cardiomyopathy (ARVC) affecting the right ventricle (Box 40-1). Clinical presentation depends on the stage of disease, and many animals with primary ventricular 214

Extracardiac

• Sepsis • Adriamycin toxicity • Malnutrition failure may remain asymptomatic for years. DCM and ARVC are discussed at length in Chapter 42.

Secondary to Other Cardiac Disease Ventricular failure can develop as a result of other cardiac diseases, either secondary to chronic pressure or volume overload. Untreated congenital diseases such as patent ductus arteriosus or ventricular septal defects result in chronic volume overload of the left side of the heart. The resultant eccentric hypertrophy, myocardial fibrosis, and decreased cardiac perfusion over time can lead to systolic dysfunction. Volume overload caused by acquired disease such as chronic degenerative valve disease (CVD) can also lead to systolic dysfunction. This sequela occurs more commonly in large breed dogs with CVD, for reasons that are not understood, and very rarely in small breeds (in which systolic function is often preserved until very late in the disease). In cats, ventricular failure is most often seen with restrictive or unclassified cardiomyopathy. It is important to note that most cats presenting with congestive heart failure (CHF) do not have underlying systolic failure. For example, in a cat presenting with pleural effusion or pulmonary edema secondary to hypertrophic cardiomyopathy (HCM), congestive heart failure occurs because of elevated ventricular filling pressure caused by diastolic dysfunction. These cases rarely develop systolic dysfunction, and positive inotropes are actually contraindicated. In the rare feline cases of HCM that do develop systolic failure, a common cause is infarcted regions of myocardium that negatively affect regional myocardial function. For a full discussion of feline cardiomyopathy, refer to Chapter 41. Chronic sustained tachycardia can also result in LV dysfunction and congestive heart failure. Tachycardia-induced cardiomyopathy is caused by persistent supraventricular or ventricular tachyarrhythmias and is characterized by systolic dysfunction and ventricular dilation.2 In most instances, rate and rhythm control will result in improved myocardial function and associated clinical signs.

CHAPTER 40  •  Ventricular Failure and Myocardial Infarction

Extracardiac Causes Systolic dysfunction can also develop secondary to several extracardiac disease processes. Sepsis can lead to myocardial depression, for reasons not completely understood. Myocardial depression occurs in almost 40% of septic human patients.3 A circulating myocardial depressant in septic shock has long been proposed, and potential candidates include cytokines, prostanoids, and nitric oxide.4 Other factors, such as decreased preload and systemic vasodilation, may contribute as well. Certain drugs, such as anthracyclines (e.g., doxorubicin), are also known to be cardiotoxic and can result in left ventricular failure with chronic use (see Chapter 49 for a full discussion). Chronic severe nutritional deficiencies in taurine, L-carnitine, and vitamin E/selenium or vegan diets can result in systolic failure (see Chapter 42). Myocarditis, or inflammation affecting the heart, may cause ventricular dysfunction and is discussed in Chapter 49. Myocarditis may be infectious (e.g., viral, bacterial, tickborne) or secondary to cardiotoxic drugs (e.g., anthracyclines).

Myocardial Infarction Although myocardial infarction (MI) is a leading cause of cardiovascular disease and death in humans, it is a relatively rare finding in small animal patients. Infarcts more commonly result secondary to systemic diseases that cause a hypercoagulable or hypofibrinolytic state.5 The wide array of associated conditions includes neoplasia, disseminated intravascular coagulation, sepsis, hyperadrenocorticism, and glucocorticoid use.5 Readers are directed to Chapter 104 for further discussion of hypercoagulable states. As mentioned earlier, MI can also be associated with end-stage feline or canine cardiomyopathies.

PHYSICAL EXAMINATION Similar to the diagnostic tests discussed later, physical examination findings are highly dependent on the stage of disease, and animals in the occult phase of cardiac disease may have no obvious abnormalities. As left-sided occult disease progresses, subtle findings such as weak femoral pulse quality as a result of decreased cardiac output may be noted by the astute clinician. As LV dilation worsens and results in stretching of the mitral valve annulus, a soft left-apical murmur may develop because of mitral regurgitation. Ventricular ectopy with concurrent pulse deficits may also be noted with palpation of the pulses during auscultation. Once the patient has clinical signs of left-sided heart failure, there is respiratory compromise, varying from an occasional cough to tachypnea or dyspnea; in severe cases of fulminant edema, liquid or foam can be seen coming from the airway. Once in congestive heart failure, tachycardia caused by sympathetic drive can often help differentiate cardiogenic edema from other causes of respiratory distress. Some physical examination findings unique to right-sided congestion include development of jugular distention or pulsation and, possibly, signs of fluid accumulation either in the pleural space or the abdomen. All these physical examination findings should be evaluated in the greater context of the patient’s presentation and history. For instance, a patient with suspected sepsis or myocarditis would also be expected to be lethargic and febrile.

DIAGNOSTIC TESTS Although electrocardiography (ECG) is the gold standard for diagnosing arrhythmias or conduction disturbances, it provides no information regarding systolic function. Depending on the underlying cause of dysfunction and secondary compensatory changes, ECGs

can give useful information regarding cardiac chamber enlargement should it be present. With ventricular hypertrophy the QRS may be prolonged, and with left-sided heart disease leads I, II, III and aVF often have tall R waves indicative of the increased LV mass. With right ventricular hypertrophy, the QRS complex is likely to have late negative deflections in leads I, II, III, and aVF, consistent with a rightwardshifted mean electrical axis. More importantly, many animals with ventricular failure may develop arrhythmias ranging from ventricular ectopy to conduction disturbances such as atrioventricular (AV) blocks or bundle branch blocks (depending on the underlying cause), ST segment changes, and so on. In severe cases, potentially lifethreatening ventricular tachycardia may develop. Thoracic radiographs (CXR) may be useful, depending on the phase of failure and the presenting complaint. Thoracic radiographs are the diagnostic tool of choice to confirm the presence of left-sided congestive heart failure (pulmonary edema). However, if a patient is in early systolic failure, the heart size and lungs may appear normal. This information may, in itself, be useful because cardiac disease would be unlikely to manifest in clinical signs with a normal vertebral heart size (VHS) (Figure 40-1) and clear lung fields.6 This would not, of course, rule out an arrhythmia as a cause of clinical signs. Also, malignant arrhythmias may develop before the development of cardiomegaly or CHF. On the other hand, suspected dysfunction secondary to sepsis would be difficult to rule out based on normal thoracic radiographs given the acute nature of the dysfunction. (There is often insufficient time for cardiac dilation or hypertrophy, so heart size may be normal on CXR.) Whatever the cause of dysfunction, as it progresses the appearance of CXR vary depending on whether the disease primarily affects the right or left side of the heart. With left-sided ventricular failure, classic cardiac findings include an increased VHS with dorsal elevation of the trachea caused by left atrial enlargement. Before or during an episode of CHF (as pulmonary venous pressure increases), pulmonary venous enlargement will develop, and eventually edema can be seen as an alveolar or interstitial pattern in the caudodorsal or

Long axis: 5.5 vertebrae

Short axis: 4.75 vertebrae

Short axis

Long axis

VHS 5.5 (long)  4.75 (short) 10.25 FIGURE 40-1  The vertebral heart size (VHS) calculation is determined by measuring the long axis and short axis of the heart as shown. These measurements are then evaluated as vertebral lengths, starting from the cranial border of the fourth thoracic vertebrae (as shown). The sum of the long axis and short axis, measured in vertebral lengths gives the VHS. For example, the VHS of the example shown is 5.5 + 4.75 = 10.25. Normal VHS values: Dog: <10.7 (for most breeds) Cat: <8.0

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PART IV  •  CARDIAC DISORDERS

perihilar lung fields. With right-sided disease such as ARVC, rightsided heart enlargement (which radiographically appears as a reverse-D cardiac silhouette on the DV or VD projection and increased sternal contact on the lateral projection) will develop before right-sided congestive signs such as enlargement of the caudal vena cava and ascites or pleural effusion. The gold standard for diagnosis of systolic failure is echocardiography. Independent of disease stage or underlying cause, ventricular dilation and decreased systolic function (increase in ventricular endsystolic dimension) will be apparent. Decreased motion of the interventricular septum or free wall may also be seen. With concurrent congestive heart failure, atrial enlargement and dilation of the pulmonary veins would also be expected. Biochemical screening abnormalities are highly dependent on the underlying cause. In regards to cardiac specific tests, biomarkers may be of some use for diagnosis of ventricular failure. B-type natriuretic peptide (BNP) is produced by myocardial tissue in response to increased pressure and wall stress and is a marker for cardiac dysfunction and heart failure. N-terminal–proBNP (NT-proBNP) may be useful to screen dogs with suspect occult systolic dysfunction.7 Cardiac troponin (cTn) is a myofibrillar protein with two diagnostically relevant forms (cTnI and cTnT) that regulate contraction of the heart.8 Blood concentrations of cTnI rise rapidly after cardiomyocyte damage, and assay of cTnI may be valuable in clinical diseases resulting in myocardial cell damage, such as myocarditis.9

PATHOPHYSIOLOGY Once a patient develops forward heart failure with clinical signs of congestion and low cardiac output, treatment can be approached using Starling’s curve (Figure 40-2). In a normal heart, as preload increases, cardiac performance also increases. However, at a certain point performance plateaus and then declines as preload continues to increase. In ventricular failure, the overall curve shifts downward, reflecting reduced cardiac performance at any given preload, and as preload increases, cardiac performance increases less. Moreover, as the heart dilates because of increased preload or the underlying cardiac disease, wall stress increases. As described by Laplace’s law

Normal

Stroke volume

216

VF with tx

VF

Preload FIGURE 40-2  As described by the Frank-Starling mechanism, in a normal heart an increase in preload results in an increase in contractility, the result being a greater stroke volume (normal curve). However, at a certain point performance plateaus, then declines. In ventricular failure (VF), the overall curve shifts downward, reflecting reduced contractility and stroke volume at any given preload. As preload increases, output increases less (blue curve). With treatment (Tx), performance is improved, although not normalized (red curve).

(wall stress = [pressure × radius] / 2 [wall thickness]), as the ventricle dilates, the resultant end-systolic and end-diastolic volumes cause increased wall stress throughout the entire cardiac cycle. Also, at any given left ventricular size (radius), the greater the developed pressure, the greater the wall stress. Increased wall stress caused by either of these mechanisms will increase the myocardial oxygen requirement and result in more myocardial energy expenditure.10 To summarize, the body’s main compensatory mechanisms for cardiac dysfunction result in fluid retention to increase preload and sympathetic stimulation to increase heart rate and cardiac output. (See Chapter 38 for further discussion of the pathophysiology of heart failure.) Although these compensatory mechanisms are initially beneficial for increasing cardiac output, chronic sympathetic stimulation and fluid retention (increased blood volume) have deleterious results (e.g., increased myocardial energy usage, etc.). The goals of treatment in forward heart failure include supporting cardiac contractility and systemic blood pressure, relieving signs of congestion, and suppressing arrhythmias, collectively maximizing cardiac output. With treatment, cardiac performance is improved, although not normalized unless the underlying cause can be addressed directly. For all inotropic drugs discussed in the next section, specific drug information is listed in Table 40-1.

TREATMENT Supporting Contractility and Maintaining Blood Pressure Positive inotropic support is essential for ventricular (systolic) failure of any cause, and many animals that develop forward heart failure will have concurrent hypotension. In patients with hypotension but without clinical or radiographic evidence of congestion, it is crucial to rule out hypovolemia as the cause. In the absence of hypovolemia, positive inotropes such as dopamine or dobutamine can be used to raise systolic blood pressure in addition to increasing contractility.10 The most commonly used positive inotropes include dobutamine, dopamine, and pimobendan. Dobutamine is a potent nonselective β agonist (with greater effect on β1 receptors) that is administered as a constant rate infusion (CRI). Because of its nonselective β stimulation, the positive inotropic effects come with some degree of peripheral vasodilation, so blood pressure must be monitored. Dopamine (the precursor of norepinephrine), when given at low doses, has effects similar to dobutamine. However, when given at high doses, concurrent α receptor stimulation results in peripheral vasoconstriction. The combination of these effects makes dopamine and dobutamine attractive options for patients in cardiogenic shock. Careful monitoring is necessary when using these drugs with ventricular failure, because systemic hypertension and elevated afterload can cause cardiac output to plummet. Both these drugs also have positive chronotropic effects, which can result in decreased time for diastolic filling as the heart rate increases. Therefore concurrent ECG monitoring of heart rate and rhythm is necessary. Other less commonly used positive inotropic sympathomimetics include norepinephrine, epinephrine, and isoproterenol (see Table 40-1). Pimobendan, an inodilator, is classified as both a calcium sensitizer and phosphodiesterase 3 inhibitor. It is a relatively new oral option for both acute and chronic inotropic support. Given its solely oral formulation, pimobendan may not be the ideal choice for an acute, severe episode of systolic failure; however, it has relatively rapid absorption and onset of effect. Pimobendan has also become widely available and may be a good option when CRIs are not feasible. Although not widely available in the veterinary setting, levosimendan and milrinone (both also phosphodiesterase 3 inhibitors) work similarly to pimobendan and are available in injectable formulations. (See

CHAPTER 40  •  Ventricular Failure and Myocardial Infarction

Table 40-110,11  Positive Inotropes Drug

Mechanism of Action

Effect

Formulation

Suggested Dose†

Dobutamine HCl*

β-Adrenergic agonist; high dose weak α agonist β 1 > β2 > α

Positive inotropy Positive chronotropy Arteriolar vasodilation Vasoconstriction (high dose)

Injectable: 12.5 mg/ml

Dog: 2-20 mcg/kg/min Cat: 1-5 mcg/kg/min

Dopamine HCl*

Dopaminergic agonist, β-adrenergic agonist, high dose α agonist Dop > β High dose α

Positive inotropy Positive chronotropy, Peripheral vasodilation Vasoconstriction (high dose)

Injectable: 40, 80, 160 mg/ml

Dog: 2-10 mcg/kg/min Cat: 1-5 mcg/kg/min Titrate to desired effect: Low dose: inotropic support High dose: antihypertensive

Norepinephrine

β-Adrenergic agonist, α agonist β 1 > α > β2

Positive inotropy Positive chronotropy Vasoconstriction

Injectable: 1 mg/ml

0.01-3.0 mcg/kg/min

Epinephrine

β-Adrenergic agonist, α agonist β 1 = β2 >α

Positive inotropy Positive chronotropy Peripheral vasodilation Vasoconstriction HD

Injectable: 1 mg/ml, 0.1 mg/ml

0.01-0.1 mcg/kg/min

Isoproterenol

β-Adrenergic agonist β 1 > β2

Positive inotropy Positive chronotropy Peripheral vasodilation

Injectable: 0.2mg/mL

Dog: 0.04-0.09 mcg/kg/min IV

Pimobendan*

Phosphodiesterase III inhibitor, Ca sensitizer

Positive inotropy Arteriolar vasodilation

Oral: 1.25, 5 mg chewable tablets

Dog: 0.25 mg/kg PO q12h Cat: 1.25 mg/cat PO q12h

Milrinone

Phosphodiesterase III inhibitor, Ca sensitizer

Positive inotropy Arteriolar vasodilation

Injectable: 1 mg/ml

0.375-0.75 mcg/kg/min

*Commonly used for inotropic support in veterinary medicine. † Consult a pharmacology textbook for complete formulation and administration specifics.

Table 40-1 for specific drug information.) Digoxin (although historically widely used in veterinary medicine as a positive inotrope for chronic therapy) has very weak inotropic properties and has been largely supplanted by pimobendan. The exception is patients in which its negative chronotropic effect is indicated, in which case digoxin can be used in conjunction with pimobendan.

Relieving Signs of Congestion Diuretics become critical should ventricular failure progress to clinical or radiographic signs of congestion, both in the acute stage and for chronic therapy. In many instances, the first knowledge of underlying ventricular failure comes when the patient develops signs of fluid overload and is presented for tachypnea, dyspnea, orthopnea, or coughing. Patients with biventricular or primarily right-sided failure may also develop ascites and abdominal distention. Furosemide is the most commonly used first-line diuretic choice (see Chapters 43 and Chapter 160 for doses). A potent loop diuretic, it works quickly to relieve life-threatening pulmonary edema, and can be given as a bolus (subcutaneously [SC], intramuscularly [IM], or intravenously [IV]) or as a CRI. With pulmonary edema, excess diuresis with overly aggressive preload reduction and relative volume depletion must be avoided.10 If possible, baseline renal values should be obtained before diuretic therapy because patients with underlying renal insufficiency may require more conservative therapy. For animals with pleural or abdominal effusion causing respiratory distress, thoracocentesis or abdominocentesis should be performed at the time of presentation. Furosemide will decrease the rate of future fluid accumulation; however, it has very little effect on existing pleural or abdominal fluid. Secondary diuretics such as spironolactone, hydrochlorothiazide, and torsemide are important in chronic therapy for refractory failure; however, at this time they are only available in an oral formulation and have limited use in the emergency room setting. For information on chronic therapy for congestive heart failure, see Chapters 42 and 43.

Suppressing Arrhythmias Despite variable underlying etiologies, many patients with ventricular failure will develop arrhythmias. All antiarrhythmic drugs can also be proarrhythmic, so it is important to note that prophylactic antiarrhythmic therapy is contraindicated in asymptomatic patients. For example, although it is common for patients to develop intermittent ventricular ectopy, only malignant arrhythmias warrant intervention. For a full discussion of antiarrhythmic therapy, see Chapters 47 and 48.

Treating the Underlying Cause Although primary cardiac disease and myocardial infarctions are generally progressive and irreversible, some causes of heart failure can be treated primarily. For example, tachycardia-induced cardiomyopathy presents a unique situation for possible resolution. Depending on the severity and chronicity, successful rate control can often result in normal systolic function. Moreover, ventricular dysfunction secondary to some extracardiac causes (such as sepsis or nutritional deficiency) may improve or normalize with therapy. However, other causes, such as doxorubicin toxicity, are generally irreversible.

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6. Buchanan JW: Vertebral scale system to measure heart size in radiographs, Vet Clin North Am Small Anim Pract 30:379, 2000. 7. Singletary GE, Morris NA, O’Sullivan L, et al: Prospective evaluation of NT-proBNP assay to detect occult dilated cardiomyopathy and predict survival in Doberman pinschers, J Vet Intern Med 26:1330, 2012. 8. Serra M, Papakonstantinou S, Adamcova M, et al: Veterinary and toxicological applications for the detection of cardiac injury using cardiac troponin, Vet J 185:50, 2010.

9. Sleeper MM, Clifford CA, Laster LL: Cardiac troponin I in the normal dog and cat, J Vet Intern Med 501, 2001. 10. Poole-Wilson PA, Opie LH: Acute and chronic heart failure: positive inotropes, vasodilators, and digoxin. In Opie LH, Gersh BJ, editors: Drugs for the heart, ed 7, Philadelphia, 2009, Saunders. 11. Smith FW, Tilley LP, Oyama MA, et al: Common cardiovascular drugs. In Tilley LP, Smith FW, Oyama MA, et al, editors: Manual of canine and feline cardiology, ed 7, St Louis, 2008, Saunders Elsevier.