Definition
Heart failure is a clinical syndrome resulting from a structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood to meet the needs of the body. This syndrome, which is a constellation of signs and symptoms, is primarily manifested by dyspnea, fatigue, fluid retention, and decreased exercise tolerance. Heart failure may result from disorders of the pericardium, the myocardium, the endocardium, valvular structures, or the great vessels of the heart or from rhythm disturbances. It is important to emphasize that not all patients with heart failure symptoms have similar cardiac structural abnormalities. Indeed, the major thrust of an initial evaluation of a patient with heart failure is to define the cardiac abnormalities responsible for the symptoms.
Classification
Heart failure has been classified in many ways. One useful framework involves describing the underlying cardiomyopa-thy, which frequently will suggest the etiology [see Table 1 and Figure 1].1-4 Some examples of the World Health Organization (WHO) classification include ischemic cardiomyopathy, hyper-trophic or restrictive cardiomyopathy, and idiopathic dilated cardiomyopathy. In the United States, the most common cause of heart failure is ischemic cardiomyopathy from coronary artery disease (CAD).5,6
Another practical approach for classification is to divide patients with heart failure into those with primarily systolic dysfunction and those with diastolic dysfunction. For the clinician, this usually means assessing the patient’s left ventricular ejection fraction (LVEF), most commonly with echocardiography.7,8 Patients with systolic heart failure typically have a low LVEF (usually less than 40% to 45%), a dilated left ventricular cavity, and a reduced cardiac output because of diminished contractility of the myocardium. In contrast, patients with diastolic heart failure have a normal LVEF and normal contractility, but there is impaired filling of the heart secondary to a variety of patho-physiologic abnormalities.9-11
Despite an increased understanding of the etiologies and pathophysiology of heart failure and advancements in treatment, morbidity and mortality remain unacceptably high for the majority of patients stricken with this disorder.12,13 Most experts agree that earlier recognition of the syndrome or better identification of patients at risk for heart failure may be our best hope for the future reduction of heart failure’s death toll. This is analogous to the concerted efforts to screen for cancer at its earliest stages, before the disease can defy therapy. Consequently, the committee charged with revising the American College of Cardiology/ American Heart Association (ACC/AHA) Guidelines for the Evaluation and Management of Heart Failure took the bold step of developing a new classification for patients with heart failure.
The ACC/AHA classification emphasizes the evolution and progression of heart failure; it defines four stages of the disorder [see Table 2 and Figure 2]. Stage A identifies patients who are at high risk for developing heart failure but who have no apparent structural abnormality of the heart. This includes patients with hypertension, diabetes, or CAD; patients with a history of rheumatic fever, alcohol abuse, or exposure to cardiotoxic drugs; and patients with a family history of cardiomyopathy. Stage B denotes patients with a structural abnormality of the heart but in whom symptoms of heart failure have not yet developed. This includes patients found to have left ventricular hypertrophy or dilatation, a decreased LVEF, or valvular disease, as well as patients with prior myocardial infarction. Stage C refers to patients with a structural abnormality of the heart and symptoms of heart failure. This would include patients with dyspnea, fatigue, or fluid overload, as well as patients with a prior diagnosis of heart failure who are receiving treatment that has relieved their symptoms. Importantly, once patients have had symptoms of heart failure, they remain in stage C even if they subsequently experience clinical improvement. Stage D includes the patient with end-stage heart failure that is refractory to standard treatment. Typical patients include those who require frequent hospital admissions for heart failure, are awaiting a heart transplant, are being supported with intravenous agents or mechanical assist devices, or are receiving hospice care for end-stage heart failure.
The ACC/AHA classification is a departure from the traditional New York Heart Association (NYHA) classification, which characterizes patients by symptom severity.15 Patients with heart failure may progress from stage A to stage D, but never the reverse. In contrast, many patients with NYHA class IV symptoms can be restored to class II with appropriate therapy. The ACC/AHA classification highlights the importance of known risk factors and structural abnormalities in the development of heart failure. Additionally, it reinforces the concept that heart failure is a progressive disease whose onset can be prevented, or its progression halted, by early identification and intervention.
Epidemiology
Heart failure is one of the major public health problems in the United States today, both in terms of the number of patients affected and health care dollars spent. Nearly five million patients have heart failure, and almost 500,000 patients are diagnosed with the disease each year. Estimated direct and indirect costs for heart failure came to $21 billion in 2001, more than 5% of that year’s health care budget16; annual spending on drugs for heart failure treatment is about $500 million.14 Hospitaliza-tions for heart failure increased by 159% from 1979 to 1998,16 and this trend will likely continue as the United States population ages.
Heart failure is primarily a disease of the elderly.17Approxi-mately 6% to 10% of people older than 65 years have heart fail-ure,18 and roughly 80% of patients hospitalized with heart failure are older than 65 years.19 More Medicare dollars are spent on heart failure than on any other disease, and heart failure is the most common Medicare diagnosis-related group.5
Table 1 Examples of Descriptive and Etiologic Classifications of Heart Failure
|
Classification Scheme |
Disorder or Disease Process |
Comments |
|
By disorder |
Dilated cardiomyopathy |
Dilatation and impaired function of left ventricle or both ventricles; multiple etiologies: ischemia, valvular disease, infectious process, inflammatory process, toxins, familial/genetic cause, idiopathic |
|
Hypertrophic cardiomyopathy |
Hypertrophy of left ventricle or both ventricles, often asymmetrical and involving the interventricular septum; often associated with mutations in sarcoplas-mic proteins; associated with arrhythmias and sudden death |
|
|
Restrictive cardiomyopathy |
Usually associated with normal systolic function and impaired diastolic function; can be idiopathic or associated with infiltrative diseases, such as amyloi-dosis, sarcoidosis, and endomyocardial fibrosis |
|
|
Arrhythmogenic right ventricular cardiomyopathy |
Replacement of myocardium with fatty tissue; can involve left ventricle as well; associated with ventricular arrhythmias; may have a genetic component |
|
|
Ischemic heart disease |
Secondary to coronary artery disease |
|
|
Valvular disease |
Caused by primary valvular disease |
|
|
Hypertension |
Usually associated with left ventricular hypertrophy; can involve systolic and/or diastolic dysfunction |
|
|
Diabetes mellitus |
Associated with systolic and/or diastolic dysfunction and left ventricular hypertrophy, even independent of coexisting hypertension or coronary artery disease |
|
|
Inflammatory/infectious disease |
Systolic dysfunction from myocarditis; multiple infectious etiologies, both viral (e.g., coxsackievirus, echovirus, HIV) and bacterial (rheumatic fever) |
|
|
By underlying disease process |
Metabolic disorders |
Associated with endocrine abnormalities (e.g., hyperthyroidism, hypothy-roidism), electrolyte deficiencies (potassium, magnesium), nutritional deficiencies (e.g., beriberi), and glycogen storage disease (e.g., Pompe disease, Gaucher disease) |
|
General systemic disease |
Associated with connective tissue diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis) and infiltrative diseases (e.g., sarcoidosis, amyloidosis) |
|
|
Muscular dystrophies |
Includes Duchenne, Becker, and myotonic muscular dystrophies |
|
|
Neuromuscular disease |
Includes Friedreich ataxia and Noonan syndrome |
|
|
Toxins |
Associated with alcohol and cocaine abuse, treatment with cardiotoxic chemotherapeutic agents (e.g., anthracyclines), and radiation therapy |
|
|
Tachycardia |
Associated with uncontrolled tachycardias (e.g., atrial fibrillation and other supraventricular tachycardias) |
|
|
Genetic/familial disorders |
Associated with a family history of cardiomyopathy and/or sudden death; many cardiomyopathies previously designated as idiopathic may fall into this category |
|
|
Pregnancy |
Manifests in peripartum period |
It is important to recognize that heart failure has diverse causes and affects diverse populations. Until recently, this diversity was not reflected in the composition of heart failure trials in the United States, which typically enrolled middle-aged white men with ischemic cardiomyopathy. In fact, the heart failure population in the United States includes significant numbers of women, elderly persons, and members of racial mi-norities—and these patients tend to have different forms of heart failure. For example, in an estimated 20% to 50% of patients with heart failure, ventricular systolic function is preserved (i.e., the patients have diastolic heart failure), and these patients are more likely to be elderly women.20-23
Etiology
CAD is responsible for roughly two thirds of cases of heart failure in the United States.24 Coronary ischemia or infarction can lead to heart failure through a variety of mechanisms: acute coronary syndromes or infarction can cause acute heart failure in an otherwise normal heart; likewise, repeated insults of ischemia or infarction can cause a chronic cardiomyopathy. Moreover, many patients with diastolic heart failure have underlying CAD.
Ventricular dysfunction can result from a multitude of non-ischemic causes [see Table 1]. These include hypertension; diabetes; valvular disease; arrhythmias; myocardial toxins; myocarditis from a variety of infectious agents (including HIV); and hypothyroidism. Infiltrative causes of ventricular dysfunction, which are usually associated with restrictive cardiomyopathy, include amyloidosis, hemochromatosis, and sarcoidosis. My-ocardial systolic dysfunction for which there is no apparent cause is labeled idiopathic cardiomyopathy. Over the past several years, there has been increased recognition that many of these so-called idiopathic dilated cardiomyopathies are familial; a number of centers are actively focusing on the identification of the genetic irregularities responsible for the abnormal phenotypes.25
Pathophysiology
There is no single, simple model that effectively explains the syndrome of heart failure; currently, the consensus view integrates multiple pathophysiologic models to explain the complex cascade of events leading to this clinical syndrome.26 The different structural, functional, and biologic changes that culminate in heart failure have led to a variety of treatment modalities to target this array of causative factors.27, 28 For example, for many years, beta blockers were contraindicated in patients with heart failure because the disorder was thought to be primarily a result of decreased myocardial contractility that would worsen with negative inotropic therapy. However, we have come to realize the central role of pathologic sympathetic activation in heart failure—the maladaptive mechanisms that lead to vasoconstriction, arrhythmias, and ventricular remodeling (see below). This model explains the therapeutic benefits of beta blockade.
The hemodynamic model of heart failure concentrated on the role of increased load on a failing ventricle; this conceptual approach led to the successful use of vasodilators and inotropes. Later, the neurohumoral model of heart failure identified the critical importance of the renin-angiotensin-aldosterone axis and the sympathetic nervous system in the progression of cardiac dysfunction, leading to widespread use of angiotensin-con-verting enzyme (ACE) inhibitors and beta blockers.
Figure 1 The different cardiac morphologies in heart failure. The heart is viewed from the left side, with the mitral valve partially cut away; the aortic valve is visible in the upper portion of the left ventricle. (a) Normal; (b) dilated cardiomyopathy; (c) hypertrophic cardiomyopathy; (d) diastolic dysfunction.
Table 2 Stages of Heart Failure14
|
Stage |
Description |
Examples |
|
A |
Patients at high risk for heart failure because of the presence of conditions strongly associated with the development of heart failure; no identified structural or functional abnormalities of the pericardium, myocardium, or cardiac valves; no current or previous history of signs or symptoms of heart failure |
Patients with systemic hypertension, coronary artery disease, diabetes mellitus, history of cardiotoxic drug therapy or alcohol abuse, history of rheumatic fever, family history of cardiomyopathy |
|
B |
Patients with structural heart disease that is strongly associated with the development of heart failure but who have no current or previous history of signs or symptoms of heart failure |
Patients with left ventricular hypertrophy or fibrosis, left ventricular dilatation or hypocontractility, asymptomatic valvular heart disease, previous myocardial infarction |
|
C |
Patients who currently have or who in the past have had symptoms of heart failure associated with underlying structural heart disease |
Patients with dyspnea or fatigue due to left ventricular systolic dysfunction; asymptomatic patients undergoing treatment for prior symptoms of heart failure |
|
D |
Patients with advanced structural heart disease and marked symptoms of heart failure at rest despite maximal medical therapy; need for specialized interventions |
Patients who are frequently hospitalized for heart failure and cannot be safely discharged from the hospital; patients in hospital awaiting heart transplantation; patients at home receiving continuous intravenous support for symptom relief or support with a mechanical circulatory assist device; patients in a hospice setting for the management of heart failure |
The recognition that progressive ventricular dilatation serves as a marker for disease progression has focused attention on the myocyte and on the role of the cardiac interstitium. Both medical and surgical therapies have been directed at this mechanism.
Left ventricular dysfunction begins with an injury to the myocardium. The unanswered question is why ventricular systolic dysfunction continues to worsen in the absence of recurrent insults. This pathologic process, which has been termed remodeling, is the structural response to the initial injury. Mechanical, neurohormonal, and possibly genetic factors alter ventricular size, shape, and function to decrease wall stress and compensate for the initial injury. Remodeling involves hypertrophy, loss of myocytes, and increased fibrosis and is secondary to both neu-rohormonal activation and other mechanical factors.29,30 Ultimately, the changes in ventricular shape lead to a less efficient cardiac pump. Functional mitral regurgitation often occurs as the left ventricle dilates and becomes more globular, increasing volume overload. Remodeling seems to beget more remodeling.
Arrhythmias often contribute to myocardial dysfunction and are an unwelcome side effect of heart failure. Supraventric-ular arrhythmias, particularly atrial fibrillation, often unmask systolic or diastolic dysfunction in a previously asymptomatic patient.31 In addition, intraventricular conduction delays and bundle branch block are often present in patients with heart failure. Abnormal ventricular conduction, particularly left bundle branch block, has significant detrimental hemodynamic ef-fects.32-35 In addition to contributing to worsening heart failure, ventricular arrhythmias are likely a direct cause of death in many of these patients; the rate of sudden cardiac death in persons with heart failure is six to nine times that seen in the general population.36
These pathophysiologic models do not easily explain dia-stolic heart failure.37 In the 20% to 50% of patients who have heart failure despite normal systolic function, cardiac output is limited by abnormal filling and disordered relaxation of the ventricles, especially during exercise. Ventricular pressures are elevated for a given ventricular volume, leading to pulmonary congestion, dyspnea, and peripheral edema identical to that seen in patients with a dilated, poorly contracting heart.9,11,38,39 CAD or ischemia frequently compounds the impairment of ventricular performance in patients with diastolic heart failure, who typically are elderly women22 with hypertension, diabetes, and obesity.
