Introduction

Essentials for Diagnosis

• Left ventricular failure: Exertional dyspnea, cough, fatigue, orthopnea, paroxysmal nocturnal dyspnea, cardiac enlargement, rales, gallop rhythm, and pulmonary venous congestion.
• Right ventricular failure: Elevated venous pressure, hepatomegaly, dependent edema; usually due to left ventricular failure.
• Assessment of left ventricular function is a crucial part of diagnosis and management.

Epidemiology
Heart failure is a common syndrome that is increasing in incidence and prevalence. Approximately 5 million patients in the United States have heart failure, and there are nearly 500,000 new cases each year.

It is primarily a disease of aging, with over 75% of existing and new cases occurring in individuals over age 65 years. The prevalence of heart failure rises from < 1% in individuals below 60 years to nearly 10% in those over age 80 years.

Pathophysiology
Systolic function of the heart is governed by four major determinants: the contractile state of the myocardium, the preload of the ventricle (the end-diastolic volume and the resultant fiber length of the ventricles prior to onset of the contraction), the afterload applied to the ventricles (the impedance to left ventricular ejection), and the heart rate.

Cardiac function may be inadequate as a result of alterations in any of these determinants. In most instances, the primary derangement is depression of myocardial contractility caused either by loss of functional muscle (due to myocardial infarction, etc) or by processes diffusely affecting the myocardium. However, the heart may fail as a pump because preload is excessively elevated, such as in valvular regurgitation, or when afterload is excessive, such as in aortic stenosis or in severe hypertension. Pump function may also be inadequate when the heart rate is too slow or too rapid. Whereas the normal heart can tolerate wide variations in preload, afterload, and heart rate, the diseased heart often has limited reserve for such alterations. Finally, cardiac pump function may be supranormal but nonetheless inadequate when metabolic demands or requirements for blood flow are excessive. This situation is termed high-output heart failure and, though uncommon, tends to be specifically treatable. Causes of high output include thyrotoxicosis, severe anemia, arteriovenous shunting (including dialysis fistulas), Paget’s disease of bone, and thiamin deficiency (beriberi).

Manifestations of cardiac failure can also occur as a result of isolated or predominant diastolic dysfunction of the heart. In these cases, filling of the left or right ventricle is abnormal, either because myocardial relaxation is impaired or because the chamber is noncompliant (“stiff”) due to excessive hypertrophy or changes in composition of the myocardium. Even though contractility may be preserved, diastolic pressures are elevated and cardiac output may be reduced, potentially causing fluid retention, dyspnea, and exercise intolerance.

When the heart fails, a number of adaptations occur both in the heart and systemically. If the stroke volume of either ventricle is reduced by depressed contractility or excessive afterload, end-diastolic volume and pressure in that chamber will rise. This increases end-diastolic myocardial fiber length, resulting in a greater systolic shortening (Starling’s law of the heart). If the condition is chronic, ventricular dilation will occur. Although this may restore resting cardiac output, the resulting chronic elevation of diastolic pressures will be transmitted to the atria and to the pulmonary and systemic venous circulation. Ultimately, increased capillary pressure may lead to transudation of fluid with resulting pulmonary or systemic edema. Reduced cardiac output, particularly if associated with reduced arterial pressure or perfusion of the kidneys, will also activate several neural and humoral systems. Increased activity of the sympathetic nervous system will stimulate myocardial contractility, heart rate, and venous tone; the latter change results in a rise in the effective central blood volume, which serves to further elevate preload. Though these adaptations are designed to increase cardiac output, they may themselves be deleterious. Thus, tachycardia and increased contractility may precipitate ischemia in patients with underlying coronary artery disease, and the rise in preload may worsen pulmonary congestion. Sympathetic nervous system activation also increases peripheral vascular resistance; this adaptation is designed to maintain perfusion to vital organs, but when it is excessive it may itself reduce renal and other tissue blood flow. Peripheral vascular resistance is also a major determinant of left ventricular afterload, so that excessive sympathetic activity may further depress cardiac function.

One of the more important effects of lower cardiac output is reduction of renal blood flow and glomerular filtration rate, which leads to sodium and fluid retention. The renin-angiotensin-aldosterone system is also activated, leading to further increases in peripheral vascular resistance and left ventricular afterload as well as sodium and fluid retention. Heart failure is associated with increased circulating levels of arginine vasopressin, which also serves as a vasoconstrictor and inhibitor of water excretion. Whereas release of atrial natriuretic peptide is increased in heart failure owing to the elevated atrial pressures, there is evidence of resistance to its natriuretic and vasodilating effects.

Myocardial failure is characterized by two hemodynamic derangements, and the clinical presentation is determined by their severity. The first is reduction in cardiac reserve, ie, the ability to increase cardiac output in response to increased demands imposed by exercise or even ordinary activity. The second abnormality, elevation of ventricular diastolic pressures, is primarily a result of the compensatory processes in systolic heart failure but is the primary derangement in diastolic heart failure.

Heart failure may be right sided or left sided. Patients with left heart failure have symptoms of low cardiac output and elevated pulmonary venous pressure; dyspnea is the predominant feature. Signs of fluid retention predominate in right heart failure, with the patient exhibiting edema, hepatic congestion, and, on occasion, ascites. Most patients exhibit symptoms or signs of both right- and left-sided failure, and left ventricular dysfunction is the primary cause of right ventricular failure. Surprisingly, some individuals with severe left ventricular dysfunction will display few signs of left heart failure and appear to have isolated right heart failure. Indeed, they may be clinically indistinguishable from patients with cor pulmonale, who have right heart failure secondary to pulmonary disease.

Although this section primarily concerns cardiac failure due to systolic left ventricular dysfunction, patients with diastolic heart failure experience many of the same symptoms and may be difficult to distinguish clinically. Diastolic pressures are elevated even though diastolic volumes are normal or small. These pressures are transmitted to the pulmonary and systemic venous systems, resulting in dyspnea and edema. The most frequent cause of diastolic cardiac dysfunction is left ventricular hypertrophy, commonly resulting from hypertension, but conditions such as hypertrophic or restrictive cardiomyopathy, diabetes, and pericardial disease can produce the same clinical picture. Although diuretics are often useful in these patients, the other therapies discussed in this section (digitalis, vasodilators, inotropic agents) may be inappropriate.

Causes & Prevention of Cardiac Failure
The syndrome of cardiac failure can be produced by many diseases. In developed countries, coronary artery disease with resulting myocardial infarction and loss of functioning myocardium (ischemic cardiomyopathy) is the commonest cause. Systemic hypertension remains an important cause of congestive heart failure and, even more commonly in the United States, an exacerbating factor in patients with cardiac dysfunction due to other causes such as coronary artery disease. A number of other processes may present with dilated or congestive cardiomyopathy, which is characterized by left ventricular or biventricular dilation and generalized systolic dysfunction. These are discussed elsewhere in this section, but the most common are alcoholic cardiomyopathy, viral myocarditis (including infections by HIV), and dilated cardiomyopathies with no obvious underlying cause (idiopathic cardiomyopathy). Rare causes of dilated cardiomyopathy include infiltrative diseases (hemochromatosis, sarcoidosis, amyloidosis, etc), other infectious agents, metabolic disorders, cardiotoxins, and drug toxicity. Valvular heart diseases - particularly degenerative aortic stenosis and chronic aortic or mitral regurgitation - are not infrequent causes of heart failure.

Because many of the processes leading to heart failure are of long standing and progress gradually, heart failure is often preventable by early detection of patients at risk and early intervention. The importance of these approaches is emphasized by guidelines that have incorporated a classification of heart failure that includes four stages (Table 10-9). Stage A includes patients at risk of developing heart failure (such as patients with hypertension or coronary artery disease) without current or previous symptoms or identifiable structural abnormalities of the myocardium). In the majority of these patients, development of heart failure can be prevented with interventions such as the aggressive treatment of hypertension, modification of coronary risk factors, and reduction of excessive alcohol intake (Figure 10-1). Stage B includes patients who have structural heart disease but no current or previously recognized symptoms of heart failure. Examples include patients with previous myocardial infarction, other causes of reduced systolic function, left ventricular hypertrophy, or asymptomatic valvular disease. Both ACE inhibitors and ß-blockers prevent heart failure in the first two of these conditions, and more aggressive treatment of hypertension and early surgical intervention are effective in the latter two. Stages C and D include patients with clinical heart failure and the relatively small group of patients who have become refractory to the usual therapies, respectively. These are discussed below.

Prognosis
Once manifest, heart failure carries a poor prognosis. The 5-year survival rate is less than 50% overall. Mortality rates vary from < 5% per year in those with no or few symptoms to > 30% per year in those with severe and refractory symptoms. In general, men have a poorer prognosis than women because they are more likely to have coronary artery disease, which is associated with a higher mortality rate, and are less likely to have diastolic heart failure, which has a lower mortality rate. These figures emphasize the critical importance of early detection and intervention. The prognosis of heart failure has improved in the last two decades, probably at least in part because of the more widespread use of ACE inhibitors and ß-blockers, which markedly improve survival.

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