Heart Failure

Heart failure is a clinical syndrome that represents a final common pathway of severe and progressive cardiac insufficiency. Heart failure is present when cardiac output is inadequate despite adequate diastolic filling pressures or when adequate cardiac output can only be maintained at the expense of elevated diastolic filling pressures. Heart failure results from the combined effects of acute or chronic cardiac insufficiency and compensatory neuroendocrine mechanisms. Heart failure manifests as either multiple organ dysfunction secondary to low cardiac output (termed low output heart failure or forward heart failure) or congestion of organs behind the heart (termed congestive heart failure or backward heart failure), or both. Congestion can occur behind the left heart, resulting in pulmonary edema or pleural effusion; or behind the right heart, resulting in ascites, peripheral edema, or pleural effusion; or both, resulting in any combination of these.

Importance of the Frank-Starling Relationship

Cardiac output (ml/min) is the total effective flow coming from the heart and is the product of stroke volume and heart rate. Stroke volume is a function of the degree of myocardial fiber shortening in the ventricle. The stretch or load on myocardial fibers just prior to contraction profoundly influences the degree of myocardial fiber shortening. This load or stretch prior to contraction is termed preload. Within limits, an increase in preload increases myocardial fiber shortening and stroke volume. Diastolic filling pressures in the heart reflect the amount of stretch or preload on the ventricle prior to contraction and, in turn, are an important determinant of cardiac output. The Frank-Starling curve describes the direct relationship between cardiac output and diastolic filling pressures (i.e., preload) in the heart (Fig. 20.1).

Figure 20.1. The Frank-Starling curve describes the direct relationship between cardiac output and diastolic filling pressures in the heart. When cardiac function is normal (upper curve), cardiac output will be adequate at normal diastolic pressures. The patient will remain "warm" and "dry" over a wide range of cardiac outputs. When cardiac insufficiency is present (lower curve), then cardiac output may be inadequate at normal diastolic pressures or cardiac output will only be adequate when diastolic filling pressures are high. In the former case, the patient is in low output heart failure or "cold". In the latter case, the patient is in congestive heart failure or "wet".

Cardiac output and diastolic filling pressures are not only functionally related, but are the physiologic parameters directly responsible for the two adverse manifestations of heart failure: namely, inadequate perfusion and congestion. The absolute amount of cardiac output is less important than the adequacy of tissue perfusion (i.e., how well cardiac output is meeting the metabolic needs of the patient). Initially, low cardiac output narrows the cardiac reserve, i.e., the ability to increase cardiac output during activity or exercise. The clinical manifestation is exercise or activity intolerance. Eventually, cardiac output can become low enough that it fails to meet the metabolic needs of organ systems and tissues even at rest. At this point, the patient is in low output heart failure. Multiple organ and tissue dysfunction are apparent. The patient is "cold" rather than "warm." While diastolic filling pressure exerts a positive influence on cardiac output, it also is the effective downstream pressure that resists venous return to the heart. Congestion occurs when diastolic filling pressure elevates capillary hydrostatic pressure to the point where a net efflux of water from capillaries to the interstitial space occurs. The result is edema of the organs and tissues behind the failing heart. The patient is "wet" rather than "dry."

Causes of Cardiac Insufficiency

Most causes of cardiac insufficiency in small animals are chronic and insidiously progressive. Cardiac insufficiency is caused by one or a combination of four basic mechanisms: primary myocardial failure, hemodynamic overload, diastolic dysfunction, or cardiac arrhythmias. From a physiologic standpoint, primary myocardial failure is a loss of systolic function associated with a decrease in cardiac contractility or an inotropic state. The most common example of primary myocardial failure in dogs is heritable dilated cardiomyopathy. Myocardial infarction is a rare cause of primary myocardial failure in animals. Hemodynamic overload results when structural defects in the heart cause it to have to do excessive work. Excess cardiac work results from the heart having to pump a high volume of blood (i.e., ) or against a high systolic pressure (i.e., pressure overload) in order to maintain an adequate cardiac output. Causes of volume overload include valve insufficiency (mitral regurgitation, tricuspid regurgitation, aortic insufficiency) and congenital left-to-right shunts (patent ductus arteriosus, ventricular septal defect, atrial septal defect). Causes of pressure overload include semilunar valve stenosis (subvalvular aortic stenosis, pulmonic stenosis) or hypertension (e.g., pulmonary hypertension). Diastolic dysfunction results from myocardial or pericardial disorders that decrease ventricular diastolic compliance (i.e., change in the pressure-volume relationship of the ventricle during diastole). Causes of diastolic dysfunction include hypertrophic cardiomyopathy, restrictive cardiomyopathy, pericardial effusion, and constrictive pericarditis. Cardiac arrhythmias can cause or contribute to heart failure by impairing cardiac output by either tachycardia or bradycardia. Tachyarrhythmias that cause or contribute to heart failure include chronic atrial fibrillation, atrial flutter, and sustained supraventricular tachycardias. Bradyarrhythmias that can cause or contribute to heart failure include third-degree atrioventricular block and persistent atrial standstill.

Response to Cardiac Insufficiency

Progression of heart disease can be arbitrarily divided into three phases. The first phase of heart disease occurs when an initiating cardiac injury or insufficiency is present. If the initiating cardiac insufficiency is acute and overwhelming, then low output heart failure may immediately ensue. More often in veterinary patients, the cardiac insufficiency is not initially overwhelming or lethal, but rather slowly progressive. The presence of heart disease may be signaled only by the presence of physical findings such as abnormal heart sounds or murmurs and not associated with overt symptoms of heart failure other than possible activity or exercise intolerance.

The second phase of heart disease is hallmarked by activation of the neuroendocrine response to cardiac insufficiency (Table 20.1). This neuroendocrine response ensures that blood pressure and cardiac output are maintained principally through the retention of vascular blood volume and the constriction of arteries and veins. Cardiac hypertrophy generally begins during this phase, particularly when the initiating cardiac insufficiency results from hemodynamic overload. The type of cardiac hypertrophy depends on the nature of the cardiac insufficiency (Fig. 20.2). During this phase, clinical evidence of cardiac insufficiency in the form of cardiomegaly occurs, although overt signs of heart failure are still not present. Symptoms would still be associated mostly with reduced activity or exercise capacity.

Figure 20.2. Cardiac hypertrophy is initially an adaptive response to hemodynamic overload in the heart. Pressure overload initiates a hypertrophic response that consists primarily of parallel replication of sarcomeres resulting in wall thickening. This pattern, termed concentric hypertrophy, normalizes afterload and thereby reduces the effect of pressure overload on the ventricle. Volume overload initiates a hypertrophic response that consists of both parallel and series replication of sarcomeres resulting in chamber dilation and wall thickening. This pattern, termed eccentric hypertrophy, increases the stroke volume capacity of the ventricle without increasing afterload. In advanced states of cardiac insufficiency, cardiac hypertrophy consists primarily of chamber dilation without wall thickening. This response, termed globoid ventricular dilation, is maladaptive because it places the ventricle at a mechanical disadvantage from the standpoint of afterload.

Although the neuroendocrine response is initially adaptive, ultimately this response becomes maladaptive. This is the third phase of heart failure. During this phase, the neuroendocrine response "overcompensates," producing high diastolic filling pressures and congestion in the form of tissue and organ edema. Inappropriate arterioconstriction is also present during this phase and may actually contribute to poor tissue perfusion. This state is termed congestive heart failure. It is possible in advanced cases of cardiac insufficiency for both congestive heart failure and low output heart failure to be present.

Neuroendocrine Theory of Heart Failure Progression

It has long been recognized that, regardless of the initiating cause of cardiac insufficiency, deleterious changes in the myocardium in the form of progressive systolic dysfunction will eventually contribute to the progression of heart failure. According to the neuroendocrine hypothesis, endogenous neuroendocrine systems activated by cardiac insufficiency are not only responsible for the deleterious hemodynamic derangements of heart failure, but also directly mediate progressive myocardial deterioration [1-3]. This myocardial deterioration takes the form of intrinsic loss of myocardial fiber contractility and, for many causes of heart failure, globoid ventricular chamber dilation. Several changes at the cellular and molecular level have been implicated in the loss of myocardial contractility, including down-regulation of beta-receptors, reversion of the cardiomyocyte to a less contractile fetal phenotype, and cardiomyocyte apoptosis. While some degree of ventricular dilation can be adaptive by increasing stroke volume capacity, particularly for volume overload, excessive ventricular chamber dilation places the ventricle at a substantial mechanical disadvantage from the standpoint of afterload, particularly when it is accompanied by thinning of the ventricular walls. In this regard, severe globoid dilation of the heart is considered a maladaptive response that contributes to heart failure progression. Evidence strongly implicates endocrine, paracrine, and autocrine mediators such as angiotensin II, aldosterone, catecholamines, endothelin, inflammatory cytokines, and peptide growth factors as mediators of or contributors to these deleterious myocardial effects. This understanding forms the current rationale for "cardioprotective" therapeutic strategies intended to slow progression toward heart failure. Drugs demonstrated to have a cardioprotective effect include angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists [2].