Approach to the Patient with Chronic Congestive Heart Failure

Chronic congestive heart failure (CHF) ranks among the most prevalent and serious of cardiac problems encountered in office practice and the most common cause of hospitalization and readmission among the elderly in the United States. The annual community rate of clinically overt CHF is about 2.3 per 1,000 for men and 1.4 per 1,000 for women; the incidence is nearly twice these figures among persons older than the age of 50 years. Five-year survival rates, regardless of cause, are poor, with mortality as low as 26% in community-based study and median survival of just 2.1 years, making the condition more deadly than many malignancies. Annual direct and indirect costs exceed $40 billion.

Effective measures are now available that improve quality of life, reduce hospitalizations, and, in some instances, prolong survival. In addition, advances in the prevention and treatment of ischemic heart disease (which accounts for more than half of CHF cases) have contributed to reducing the CHF disease burden. Over the past decade, 1-year risk-adjusted mortality declined from 31.7% to 29.6%; hospitalizations fell by 29.5%. Despite this progress, CHF remains a pressing problem, especially with regard to CHF associated with diastolic dysfunction, which accounts for upward of 50% of cases.

The primary care physician’s tasks include making the initial diagnosis of CHF and differentiating it from other causes of dyspnea (see also Chapter 40), identifying its underlying
pathophysiology, and designing an appropriately matched basic treatment program, patient education, support, and monitoring. Central to success of the mission are the contributions of the medical home team, community-based caregivers, and a readily available cardiac consultation. The ability to improve outcomes has made CHF a focus of quality improvement efforts and performance-based payment initiatives.

PATHOPHYSIOLOGY, CLINICAL PRESENTATION, AND COURSE (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 and 28)

Pathophysiology

Impairment of left ventricular (LV) function, be it systolic and/or diastolic, constitutes the pathophysiologic common denominator of CHF. Almost half of heart failure cases result from classically described reduction in LV ejection fraction (EF), the so-called systolic dysfunction, designated as systolic heart failure or, more recently, heart failure with reduced ejection fraction [HFrEF]). Over the past two decades, the role of reduced LV filling and associated deficits, the so-called diastolic dysfunction, has emerged as an equally important contributor to the pathophysiology of CHF and is referred to as diastolic heart failure or heart failure with preserved ejection fraction (HFpEF). Many cases have elements of both, but usually one mechanism predominates, with consequences for diagnosis and management.

Heart Failure with Reduced Ejection Fraction: Systolic Dysfunction

The traditional hallmark of CHF—systolic dysfunction—follows a myocardial insult that impairs contractility, classically a myocardial infarction. The LV EF is significantly reduced (EF, <0.40), and LV dilatation often ensues. Although the leading cause is myocardial infarction, any insult that damages the left ventricle’s systolic pump function (e.g., myocarditis, dilated cardiomyopathy, some forms of valvular heart disease) can produce a similar pathophysiology. In community-based observational study, about 50% to 60% of CHF cases were due to systolic dysfunction, which also accounts for 60% of the mortality risk. In such cases, an element of diastolic dysfunction may accompany the systolic component, but the latter typically predominates.

Heart Failure with Preserved Ejection Fraction: Diastolic Dysfunction

As much as 50% of CHF in the community setting is attributable to diastolic dysfunction. The pathophysiologic hallmarks are described as defective diastolic myocardial relaxation (an active, energy-dependent process) and loss of myocardial distensibility, which impair LV diastolic filling. LV systolic function may also be compromised, but the LV EF remains better preserved than in systolic heart failure (EF, >45% to 50%). Other abnormalities include endothelial dysfunction, abnormal vascular reactivity, and electrical disturbances; pulmonary hypertension may ensue. Ventricular remodeling (with myocyte hypertrophy and myocardial fibrosis) is thought to contributes to the problem. LV wall thickness increases, but end-diastolic volume remains unchanged. The velocity of blood flow across the mitral valve becomes abnormal, reflecting poor diastolic relaxation and reduced ventricular distensability.

Abnormal diastolic filling reduces cardiac output, especially during exercise, and raises pulmonary venous pressures, contributing to pulmonary venous congestion, dyspnea, and peripheral edema. Compensatory left atrial contractility may increase by as much as 50% to help preserve diastolic filling, but persistent elevations in atrial pressure lead to atrial enlargement, the substrate for atrial tachyarrhythmias, which limit diastolic filling time (so important to coronary perfusion and cardiac output). Compensatory cardiac and neurohumoral responses initially help to maintain cardiac output, but ultimately they prove to be dysfunctional and exacerbate the problem, leading to LV remodeling and further reduction in LV function. The resultant LV impairment may include delayed myocardial activation and dyssynchronous contraction (dyssynchrony), leading to severe, persistent symptoms.

Compensatory Responses

Some compensatory mechanisms are specific to the underlying pathophysiology, and others result from the fall in cardiac output.

Cardiac Responses

The principal myocardial response is a remodeling of the left ventricle. At the microscopic level, there is cell dropout, presumably from accelerated programmed cell death (apoptosis), dissolution of the supporting collagenous matrix, and myocyte hypertrophy; myocyte “slippage” may ensue. If the precipitating insult produces abnormal loading conditions (as in myocardial infarction or valvular insufficiency), the left ventricle responds predominantly by dilating (some hypertrophy may also occur); over time, the LV becomes spherical. Hypertrophic responses may predominate when there is increased afterload, as in cases of diastolic heart failure. The permanently remodeled myocardium is fibrotic and dysfunctional.

Systemic Responses

The initial fall in cardiac output from the index event activates the renin-angiotensin-aldosterone system and triggers heightened sympathetic activity, resulting in sodium retention, vasoconstriction, and elevations in heart rate, preload, and afterload. In the failing heart, the result is pulmonary and systemic hypertension but no improvement in cardiac output. These cardiac and neurohormonal responses temporarily help to maintain cardiac output by way of the Frank-Starling mechanism but at the cost of inducing volume overload and stimulating progressive LV remodeling (α-adrenergic stimulation is a potent mediator of cardiac myocyte hypertrophy). The progressive decrease in cardiac output triggers further neurohumoral activity, and a vicious cycle is established. High serum levels of renin, angiotensin, and norepinephrine are associated with increased 5-year mortality rates. Similarly, vasopressin levels rise as LV function declines, increasing preload, filling pressures, and afterload. It triggers cardiac remodeling that results in myocardial hypertrophy, fibrosis, and decreased contractility.

Counterregulatory Responses

In response to volume overload, atrial and ventricular tissues release natriuretic peptide, which increases glomerular filtration and inhibits the secretion of renin and aldosterone, promoting vasodilation and the excretion of sodium and water. Sympathetic overactivity leads to down-regulation of β₁–adrenergic receptors and blunted β-receptor signaling. Prostaglandin synthesis and kinin release promote vasodilation and renal sodium excretion. Although they are helpful, these counterregulatory changes are usually insufficient to overcome the powerful maladaptive neurohumoral responses triggered by heart failure.

Risk Factors

In community-based population studies, the leading independent risk factors for CHF are hypertension, smoking, diabetes
(independent of ischemic disease), obesity, and ischemic heart disease. Elevations in systolic blood pressure and pulse pressure are important predictors, as is the presence of valvular disease (particularly aortic or mitral). A parental history of heart failure is associated with an increased prevalence of LV dysfunction and heart failure in offspring, suggesting a strong influence of familial and genetic factors. Less-well-established independent risk factors include renal dysfunction in older patients (creatinine >1.4 mg/dL), loss of diurnal variation in blood pressure, hyperinsulinism, subclinical hypothyroidism (thyrotropin >7.0 mIU/L), and excess salt intake in obese persons. High and low levels of circulating estrogens have been linked to increased mortality in CHF, and correction of iron deficiency significantly improves functional status, suggesting a contributing role for low iron levels. Commonly used drugs such as nonsteroidal antiinflammatory drugs (NSAIDs) (with their potential for adverse cardiovascular and renal effects—see Chapter 156) may precipitate or worsen heart failure and increase rate of rehospitalization and risk of death.

In diastolic heart failure, the principle risk factors are hypertension, atrial fibrillation (AF), insulin resistance, older age, female sex, and dyslipidemia; women outnumber men 2:1. In systolic heart failure, important predictors include ischemic heart disease, smoking, and diabetes.

Clinical Presentation

The classic “congestive” manifestations of established CHF— leg edema, orthopnea, paroxysmal nocturnal dyspnea, rales, and jugular venous distention—are clinical features common to both systolic and diastolic dysfunction. However, some elements of the presentation differ according to stage of the disease and whether the predominant ventricular pathophysiology is systolic or diastolic.

Presentation by Stage of Disease

The evolving appreciation for the progressive nature of CHF has led to designation by the American College of Cardiology and American Heart Association of a staging system for CHF, with the implication that, like cancer, the disease progresses in irreversible although not necessarily inexorable fashion.

Stage A patients typically have major risk factors for coronary disease or early valvular disease but no symptoms or manifestations of LV structural change. Nonetheless, they are at high risk, which can be ameliorated by tight control of the relevant CHF risk factors (e.g., see Chapters 26, 27, 33, and 102).

Stage B is characterized by the early evidence of structural and functional changes but no overt symptomatology. LV hypertrophy or dilation, reduced EF, or impaired diastolic filling may be noted on cardiac ultrasound. Here, too, timely intervention may prevent disease progression. It is estimated that nearly 50% of CHF patients are in stage B, but many of these go undetected.

Stage C represents further disease progression. Patients may initially complain of fatigability, dyspnea on exertion, or unexplained weight gain. At this early phase of stage C, there may be few overt physical signs of failure, but chest x-ray often shows pulmonary congestion (redistribution of pulmonary venous flow to the upper lung fields) and/or cardiomegaly. Fatigue becomes increasingly prominent as cardiac output falls. As pulmonary congestion increases, exertional dyspnea worsens and orthopnea is noted, and rales may become evident on auscultation of the lungs, but their absence does not rule out the presence of CHF. Mild ankle edema may be noted, but pedal edema is one of the least specific signs of CHF (see Chapter 22).

Stage D and the later phases of stage C are characterized by paroxysmal nocturnal dyspnea, worsening ankle edema, jugular venous distention, and hepatojugular reflux, all of which are indicative of markedly elevated pulmonary and systemic venous pressures (pulmonary capillary wedge pressure at least 15 mm Hg). As LV dilation progresses, functional mitral insufficiency may become evident. An S₃ (third heart sound) gallop may be heard, indicative of advanced LV failure and predictive of poor prognosis (relative risk, 1.3). Sometimes, failure-induced bronchospasm dominates the pulmonary examination. The chest film will often show interstitial pulmonary edema; right-sided or bilateral pleural effusions are common.

Acute exacerbation requiring hospital admission is usually preceded by a period of decompensation characterized by increasing dyspnea, worsening edema, and weight gain. In many instances, the cause is dietary indiscretion or noncompliance with medication. The interval between the onset of clinical worsening and the need for hospitalization is about 1 week, allowing time for the detection and treatment of reversible factors and the avoidance of admission.

Presentation by Underlying Pathophysiology

Patients with systolic dysfunction tend to be male, aged 50 to 70 years, with a history of myocardial infarction, an audible S₃, signs of LV dilation, a chest x-ray showing cardiomegaly with congestion, and an EF of less than 0.40. Onset is typically gradual.

Those with diastolic dysfunction are more likely to be older, female, obese, and with a history of diabetes and hypertension—90% of patients presenting with heart failure and preserved LV EF have hypertension, and the majority are women. In these patients, exercise intolerance is prominent, due to both shortness of breath from pulmonary venous hypertension and fatigue from poor cardiac output. Onset may be rapid, as in “flash pulmonary edema” seen with exercise or onset of rapid AF. There is often an audible fourth heart sound (S4) and an LV lift without evidence of dilation; venous congestion is prominent on chest x-ray without cardiomegaly. The EF is typically well-preserved (>40%).

Atypical Presentations

The efficacy of potent modern diuretic therapy has created an atypical but common clinical presentation sometimes referred to as “cold and dry.” In this state, cardiac output remains low (the extremities feel cool), but characteristic congestive manifestations are absent. Complaints of fatigue might dominate the clinical picture, whereas dyspnea, orthopnea, leg edema, rales, and even radiologic signs of CHF (see later discussion) may be absent.

Clinical Course, Prognosis, and Determinants of Prognosis

Untreated or inadequately treated, the clinical course tends to be progressive, determined in part by the rate and extent of LV remodeling. However, CHF is not a single disease, and, therefore, it does not have a uniform natural history. As noted, overall prognosis is poor, with 5-year survival from onset of symptoms less than 50%. Prognosis is somewhat better for those with preserved EF, but mortality and morbidity remain substantial, with rates of readmission, functional decline, and dyspnea post discharge from the hospital similar to those with reduced EF. As noted, diastolic dysfunction may occur in either the absence or presence of systolic dysfunction. Its presence worsens prognosis, especially when moderate or severe, and serves as an independent determinant of outcomes.

The clinical course and response to therapy vary considerably from person to person according to such determinants
as underlying etiology, state of the myocardium at the time of presentation, stage of illness, and the patient’s functional capacity. In addition, renal function plays a critical role in prognosis, which is significantly worsened by the onset of renal failure. Part of the variability in clinical course and response to therapy is believed due to genetic factors, which account for racial and familial differences. Genetic polymorphism (or sequence variation) in genes controlling both renin-angiotensin and adrenergic signaling has been linked to variations in disease progression and clinical responses to angiotensin-converting enzyme (ACE) inhibitors and beta-blockers.

Diastolic dysfunction contributes independently to all-cause mortality (reported hazard ratios range from 1.8 to 10). Although its annual mortality rate (reported at 8%/year to 17%/year) is only half of that of systolic dysfunction, it makes a significant contribution to adverse cardiac outcomes and accounts for about 40% of CHF morbidity and mortality. The presence of a third heart sound and hepatojugular reflux increases the risk of an adverse cardiac event by nearly 30% each.

Similarly, increases in plasma norepinephrine, BNP, NT-proBNP, and copeptin levels correlate strongly with mortality risk, representing compensatory responses to a failing heart. Anemia has been linked to outcome, with each 1% fall in hematocrit correlating with a 2% rise in 1-year mortality.

DIAGNOSIS, CLASSIFICATION, AND RISK STRATIFICATION (6,10,18,21,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 and 42)

Clinical recognition of heart failure can be difficult. Early stages of the condition produce few symptoms or signs, and CHF can be hard to differentiate from other causes of acute dyspnea. Many of the symptoms of CHF (which are often the manifestations of compensatory mechanisms) are nonspecific and at times misleading, which results in both overdiagnosis and underdiagnosis. As many as 40% of patients being treated on clinical grounds for CHF do not fulfill the basic echocardiographic criteria for the condition, whereas more than half of CHF patients go undetected. Consequently, practical laboratory aids to clinical diagnosis have been sought.

Clinical Diagnosis

As noted, most symptoms and signs are individually neither very sensitive nor specific, but taken together, they can provide a reasonable estimate of pretest probability and aid in test selection and interpretation.

Clinical Criteria

Clinical features identified in the Framingham Heart Study as having the greatest predictive value and capable of serving as major criteria for the diagnosis of CHF include the following:

Paroxysmal nocturnal dyspnea
Orthopnea
Elevated jugular venous pressure
Presence of rales (crackles) on chest exam
Third heart sound
Cardiomegaly or pulmonary edema on chest x-ray
Weight loss of 10 lb in 5 days in response to treatment for CHF

Other findings that make a lesser contribution to diagnosis (minor criteria) include peripheral edema, nocturnal cough, exertional dyspnea, hepatomegaly, pleural effusion, and tachycardia (heart rate >120 beats/min).

The earliest findings (fatigability, dyspnea on exertion, unexplained weight gain) are quite nonspecific. A story of orthopnea or paroxysmal nocturnal dyspnea is much more suggestive, as is the finding of basilar rales on pulmonary examination (although the absence of rales does not rule out CHF [negative predictive value, 35%]). The finding of S₃ is among the most specific of physical signs (the specificity for systolic dysfunction approaches 90%), but it is often difficult to elicit and may not be present in early or mild disease (sensitivity <35%); it also can occur in the absence of LV failure in elderly patients with hypertension and those with valvular mitral regurgitation. Hepatojugular reflux (sometimes referred to as abdominojugular reflux) has a specificity of almost 95% but a sensitivity of less than 25%. The presence of any three major criteria (e.g., S₃, cardiomegaly, basilar rales) constitutes reasonable presumptive evidence for the diagnosis.

The assessment of volume status can be difficult; orthostatic signs are sensitive for the detection of dehydration, but the detection of volume overload is more problematic unless it is marked. Blood pressure response to the Valsalva maneuver has been proposed as an improved means for assessing volume overload status. As volume increases, there is an exaggerated increase in the initial rise in blood pressure that occurs shortly after the onset of bearing down but a loss of the rebound increase in blood pressure that typically occurs after relaxation. This can be elicited by inflating the blood pressure cuff to 15 mm Hg above systolic pressure during normal respiration and listening for the return of Korotkoff sounds during and after the Valsalva maneuver.

Clinical Recognition of Systolic and Diastolic Dysfunction

Identifying the underlying pathophysiology can facilitate management, but making the diagnosis and distinguishing between systolic and diastolic dysfunction on clinical grounds can be difficult because the symptoms and signs can be similar in both forms of heart failure and both may coexist in the same patient. Systolic dysfunction and its associated LV dilation may be manifested by a third heart sound, laterally displaced apical impulse, and a mitral regurgitant murmur. Signs of systemic venous hypertension (jugular venous distention, leg edema) may be prominent. In diastolic heart failure with its associated LV hypertrophy, there may be a fourth heart sound and an LV lift or heave but little lateral displacement of the apical impulse. Due to resistance to diastolic filling, signs of systemic venous hypertension may become evident earlier but are usually not as prominent as in systolic dysfunction.

Laboratory Diagnosis

The absence of diagnostic clinical findings in early stages of CHF and the lack of diagnostic sensitivity and specificity for those manifestations that develop later lead to dependence on laboratory testing, especially functional cardiac imaging.

Chest X-Ray

The plain chest film remains an excellent, readily available test for the initial diagnosis of CHF. Characteristic findings include upper zone flow redistribution (“cephalization”), cardiomegaly, and signs of interstitial edema (prominent interstitial markings, Kerley “B” lines, and perihilar haziness). Patients who develop CHF only during exertion may not show characteristic interstitial edema changes on plain film, but cardiomegaly and upper zone redistribution may be present. The sensitivity of the chest film for cardiomegaly is about 80%.

Cardiac Doppler Ultrasound Study

Heart failure diagnosis and management benefit greatly from the use of cardiac ultrasound. When combined with Doppler study (for the determination of blood flow), ultrasound provides determinations of EF, chamber size, wall thickness, and diastolic filling, as well as detection of valvular and wall motion abnormalities, greatly extending the information obtained by clinical assessment and chest x-ray. It is the test of choice for the detection of diastolic dysfunction (EF >0.45, reduced diastolic filling) and can help to reveal its cause (e.g., LV hypertrophy, ischemia). It is also an effective means of diagnosing systolic dysfunction (EF <0.40, LV dilation, mitral regurgitation). The test is the procedure of choice for the assessment of suspected CHF, both systolic and diastolic; it makes possible detection of CHF in the preclinical stages of illness (when intervention may be the most efficacious) and differentiation of systolic from diastolic disease. Despite its great utility, the test is underutilized in community practice.

B-Type Natriuretic Peptide Levels

The natriuretic peptides are released by cardiac tissue and the brain in response to the vasoconstriction and sodium retention that accompany CHF; they correlate with increases in ventricular pressure and volume and with diastolic filling pressures. In the setting of acute dyspnea, they correlate strongly with the diagnosis, severity, and prognosis of CHF. Levels are greatest in systolic dysfunction, but they are also elevated in diastolic disease, although to a lesser extent. Two assays are available: B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (NT-proBNP). Test characteristics include a sensitivity of 90% and a specificity of 76%; the positive predictive value in the setting of suspected CHF is 79%, and the negative predictive value is 89%. Compared with other history, physical, and laboratory findings for CHF, natriuretic peptide elevation is among the most predictive of CHF (odds ratio, 29.6). A BNP <100 pg/mL in a dyspneic patient virtually rules out heart failure (be it systolic or diastolic). A NT-proBNP of >900 pg/mL in a person more than 50 years of age is both sensitive and specific for the diagnosis of acute heart failure.

Serum levels do not correlate with EF, but the tests’ high sensitivities can help determine who should undergo echocardiographic testing; however, economic modeling suggests that when pretest probability is high, it is more cost-effective to proceed directly to cardiac ultrasound. Measurement of natriuretic peptide has also been suggested as a means of improving prognostication (see later discussion); its use in monitoring of therapy is not established. Causes of increased BNP other than heart failure include advancing age, renal dysfunction (natriuretic peptide BNP cleared renally), pulmonary embolism, and pulmonary hypertension. Obesity reduces BNP.

Choice of Natriuretic Peptide Study.

Both BNP and NT-proBNP can be measured conveniently by rapid assay. Use of the NT-proBNP is preferred in cases of acute heart failure, especially that due to suspected HFpEF, because of a 20% false-negative rate for the BNP assay in this setting.

Electrocardiogram

The electrocardiogram (ECG) is not particularly sensitive or specific for the diagnosis of CHF, but its ready availability, low cost, and capacity to detect important cardiac findings associated with CHF and its causes (AF, prior myocardial infarction, LV hypertrophy, left-bundle-branch block, left atrial enlargement) make it a useful adjunct to workup, with likelihood ratios in the range of 2 to 4. The absence of ECG abnormalities reduces the probability of heart failure (negative likelihood ratio, 0.65).

Classification and Risk Stratification

CHF patients can be classified by functional status and stage of disease, which facilitates risk stratification. Biomarkers such as BNP are being explored as a means of enhancing assessment of prognosis.

By Functional Status

The traditional approach to classification of CHF patients has been to use the New York Heart Association (NYHA) functional classification system: Class I patients are asymptomatic, class II patients have symptoms only with marked exertion, class III patients have symptoms with more modest activity, and class IV patients have symptoms at rest. Most studies of CHF select patients by functional class. Functional class is also a determinant of prognosis. In persons with a low EF, yearly mortality is 10% to 15% for class II patients, 15% to 25% for class III patients, and 30% to 50% for class IV patients.

By Stage of Disease

As noted earlier, the recognition of the progressive nature of CHF has led to the AHA/ACC classification by stage of disease, which can be useful as an aid to management and prognosis and is referred to increasingly in the literature and in clinical guidelines:

Stage A: At high risk of developing CHF, but asymptomatic and no discernible structural or functional abnormalities
Stage B: Structural abnormality, but no symptoms or signs
Stage C: Structural abnormality and symptoms of heart failure
Stage D: Advanced structural heart disease and marked symptoms at rest despite maximal medical therapy

By Biomarkers

Biomarkers (e.g., BNP, NT-proBNP, copeptin [a C-terminal fragment of provasopressin]) are being explored not only for diagnosis but also for determination of prognosis, particularly risk of cardiovascular death. When incorporated into risk determinations that include clinical parameters and NYHA functional class, such markers can improve prognostication by as much as 10% to 20% (area under the ROC curve as high at 0.76), especially when two pathophysiologically distinct markers (e.g., NT-proBNP and copeptin) are used in combination. More validation work is needed, but biomarkers hold promise as a means of enhancing risk stratification.

PRINCIPLES OF MANAGEMENT (6,7,21,27,39,40,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104 and 105)

Overview of Strategy

The basic elements of the management strategy are attending to risk factors, underlying etiologies, and precipitating factors and treating etiologically and pathophysiologically as early and as intensively as possible. Although CHF can be progressive and inexorable, it is often preventable and sometimes reversible, especially in its early stages—underscoring the importance of prevention as well as early diagnosis and treatment.

Prevention: Screening for and Treating Risk Factors

Because the lifetime risk after age 40 of developing heart failure is about 1 in 5, screening for and treating major modifiable risk factors for CHF is a priority for primary care practice.

Screening.

Screening can be carried out by use of a scoring system derived from the community-based Framingham Heart Study. Elements of this validated instrument for estimating probability of developing CHF include age, systolic blood pressure, heart rate, LVH on ECG, evidence of coronary or valvular heart disease, diabetes, cardiomegaly on chest x-ray, and forced expiratory capacity (http://www.framinghamheartstudy.org/risk/heartfailure/htr). In persons with CHF risk factors, use of the BNP can also identify candidates for early intervention and help overcome the all-too-prevalent underutilization and delay in implementation of effective therapies for CHF prevention.

Treatment of Risk Factors.

Morbidity and mortality benefits are considerable from timely and aggressive treatment of major risk factors. Included are attention to hypertension (see Chapters 14, 19, and 26), hyperlipidemia (see Chapters 15 and 27), coronary artery disease (see Chapters 20, 30, and 31), diabetes mellitus (see Chapters 94 and 102), thyroid disease (both hyper- and hypothyroidism) (see Chapters 103 and 104), valvular heart disease (see Chapter 33), and tachycardias, especially rapid AF (see Chapter 28). Statins, ACE inhibitors, and other antihypertensive agents have been found particularly beneficial in at-risk populations.

Attention to lifestyle is also important, given the prominent contributing roles of diet, exercise, alcohol, tobacco, and substance abuse toward major underlying etiologies of heart failure. Maintaining a normal body weight, refraining from smoking, exercising regularly, consuming alcohol moderately, and taking a diet that includes breakfast cereals, fruits, and vegetables reduce lifetime risk after age 40 from 21.2% (adhering to none of these measures) to 10.1% (adhering to at least 4 of the 6). Diet alone can have an important impact. Adherence to the DASH diet (high intake of fruits, vegetables, low-fat dairy products, and whole grains) is associated with a 37% lower risk of heart failure. Similar benefits may accrue from eliminating high dietary sodium intake. Serum levels of omega-3 fatty acids from consumption of oily fish, nuts, and vegetables correlate inversely with risk of developing heart failure. Abstinence from alcohol may reverse LV dysfunction in persons who abuse alcohol; abstinence from cocaine and smoking reduces risk of ischemic injury leading to heart failure.

Correction of Precipitating Factors

Attention to precipitating factors is another priority. Both illness and medications can trigger or worsen heart failure.

Concurrent Illnesses and Stresses.

Acute ischemia (see Chapter 30), severe anemia (see Chapter 82), high fever (see Chapter 11), rapid AF and other supraventricular tachycardias (see Chapter 28), pneumonia (see Chapter 52), pulmonary embolization (see Chapter 35), inadequately controlled thyroid disease (see Chapters 103 and 104), excess salt intake, and emotional stress (see Chapter 31) may worsen or precipitate failure in patients with decreased myocardial reserve. Obstructive sleep apnea may exacerbate the neurohumoral stimuli of heart failure; continuous positive airway pressure (CPAP) can improve the EF, but its effects on CHF outcomes remain to be established. Correction of iron deficiency in anemic patients can be helpful (see later discussion). Statin therapy reduces the risk for death and hospitalization independent of the presence of underlying coronary disease. While chronic alcohol abuse is an important risk factor for cardiomyopathy and tachyarrhythmias (see Chapter 28), acute intake of alcohol has no deleterious effect on cardiac function (unless it induces a tachycardia).

Limiting Medications with Potentially Adverse Effects.

Review of medications is also essential for potentially harmful agents commonly used for other conditions by patients with heart failure. Most important are the calcium-channel blockers and NSAIDs.

Calcium-Channel Blockers.

These coronary vasodilators are widely prescribed for use in coronary disease (see Chapter 30) and hypertension (see Chapter 26); consequently, many heart failure patients may already be taking them. Most calcium-channel blocker use in patients with heart failure is associated with increased risks of worsening heart failure, life-threatening arrhythmias, myocardial infarction, and death (particularly in patients with coronary disease and a low EF). Purported mechanisms include reflex tachycardia and negative inotropic activity, but use of preparations relatively free of these effects does not necessarily lower the risk (see Chapter 30). Of the calcium-channel blockers, only amlodipine has been proven to be safe for use in anginal patients with severe chronic LV dysfunction (EF <0.30). Of the drugs in its class, it appears to have the least effect on contractility, conductivity, and neurohumoral reflexes, but precisely why it is the best tolerated of the calcium-channel blockers in CHF remains unclear. Despite its being better-tolerated, amlodipine does not improve survival and carries a 5% risk of inducing pulmonary edema; bothersome leg edema is common, especially in warm weather. Those who develop CHF while taking a calcium-channel blocker for angina or hypertension should be switched to agents whose benefits extend to CHF (e.g., ACE inhibitors, angiotensin receptor blockers [ARBs], beta-blockers). If calcium-channel-blocker therapy is deemed essential (e.g., persistent angina), one should consider amlodipine and obtain cardiac consultation.

NSAIDs.

By interfering with prostaglandin synthesis through COX inhibition, these drugs can cause sodium retention, volume overload, azotemia, and impairment of coronary vasodilation (see Chapter 156). Mortality and morbidity in persons with chronic heart failure rise with dose and degree of NSAID COX-2 inhibitory activity; hazard ratios range from 1.22 for naproxen to 1.75 for celecoxib.

Cardiotoxic Chemotherapy Agents.

Minimizing use of cardiotoxic antitumor agents in seriously ill cancer patients is obviously a difficult challenge, but close monitoring of cardiac status (including use of cardiac ultrasound) can help guide therapy, minimize damage to the myocardium, and preserve LV function (see Chapter 88).

Treating Pathophysiologically

The treatment program should reflect and address the basic underlying pathophysiology of the patient’s heart failure, be it systolic and/or diastolic dysfunction or problematic compensatory mechanisms, such as activation of the renin-angiotensin system.

Treatment of Systolic Heart Failure.

Treatment is directed at countering the adverse neurohumoral compensatory responses (volume overload, increased adrenergic activity, ventricular remodeling) that result from and worsen systolic heart failure. Patients can achieve symptomatic relief, improved functional status, reduction in hospitalizations, and extended survival with early initiation of angiotensin blockade and beta-blockade, supplemented by diuretic therapy for relief of symptoms related to volume overload. Use of an angiotensin-converting enzyme inhibitor (ACE inhibitor) or an ARB counters the heightened activity of the angiotensin-renin-aldosterone system, reducing both preload and afterload. Prior to the advent of ACE inhibitors, the combination of hydralazine and isosorbide was used to achieve this goal but did so at the cost of inducing a reflex tachycardia and hypotension, compromising its beneficial effects and relegating its use to refractory situations, particularly in African Americans (see later discussion). Beta-blockers blunt the excessive catecholamine response, slowing heart rate and reducing the stimulus to remodel. Although the use of beta-blockade may seem paradoxical in the setting of a reduced EF, its use actually improves hemodynamics and survival.

When applied in a timely fashion, such therapies have the potential to improve symptoms and outcomes across a wide range of patients. In advanced stages of heart failure, direct
aldosterone inhibition and cardiac glycoside (e.g., digoxin) therapy can help symptomatically and reduce rates of hospitalization; mechanisms of action probably extend beyond diuresis and enhanced contractility to effects on remodeling and neurohumoral responses. Survival is enhanced with aldosterone inhibition, but not with digoxin. As noted, the avoidance of calcium-channel blockers (with the exception of amlodipine) and NSAIDs is essential because these drugs can precipitate cardiac decompensation and fluid retention.

Treatment of Diastolic Heart Failure.

At the present time, no CHF treatment has emerged that definitively prolongs survival for patients with HFpEF. Unlike HFrEF, where renin-angiotensin blockade is associated with reduced all-cause mortality, treating HFpEF patients with ACE inhibitors or ARBs in randomized controlled trials has so far not achieved this important primary outcome. Critics point to shortcomings of available studies (e.g., lack of power, underrepresentation of patents with more severe heart failure) and positive results from subsequent meta-analyses and large-scale observational study to suggest that a survival benefit from use of angiotensin blockade will eventually be demonstrated. The literature should be watched for new data.

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