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Heart FailureJames O. Mudd, MD; Michael Field, MD; and Edward Kasper, MD

FAST FACTS

� The most common causes of heart failure (HF) in the United Statesare ischemic heart disease, hypertension, valvular heart disease, andidiopathic dilated cardiomyopathy.

� HF may result from impaired systolic function, impaired diastolicfunction, or a combination of the two.

� A patient’s hemodynamic status can be classified based on thepresence or absence of pulmonary congestion (wet or dry) and thepresence or absence of poor perfusion (cold or warm).

� Diuretic therapy is the cornerstone of treatment in both acute andchronic HF.

� Angiotensin-converting enzyme (ACE) inhibitors are indicated in allcases of left ventricular dysfunction, improving both symptoms andsurvival.

� Beta-blocker therapy improves survival and symptoms in patientswith New York Heart Association class II to IV HF.

� Digoxin therapy improves symptoms and rehospitalization rates butnot mortality in patients with HF.

� Aldosterone blockade therapy improves survival and symptoms inselected patients with HF.

� Implantable cardioverter-defibrillators (ICDs) and cardiacresynchronization therapy provide survival benefit in patients withreduced left ventricular function.

I. EPIDEMIOLOGY1. The prevalence of HF continues to grow, resulting in significant

morbidity and mortality. Current estimates suggest that more than 5million people have this syndrome, and another 400,000 to 700,000develop HF each year.1

2. HF is a syndrome in which the heart cannot meet the metabolicdemands of the body or fails to maintain adequate cardiac output in theface of rising filling pressures. Cardiomyopathy, on the other hand, is adisease of heart muscle that may or may not lead to HF. Box 11-1 liststhe major forms of cardiomyopathy.

3. HF is further subclassified into systolic and nonsystolic (diastolic) HF.Approximately 30% to 50% of patients with HF have preserved leftventricular function.2 Nonsystolic HF is defined as a clinical syndromewith signs and symptoms of HF in the setting of normal left ventricularejection fraction (more than 50%) and the absence of valvular disease.Nonsystolic HF is heterogeneous and is caused by impaired left

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ventricular relaxation, increased left ventricular stiffness, or impairedventricular-arterial coupling. Often, both systolic and nonsystolic HFcoexist. Furthermore, all patients with systolic HF have some degree ofdiastolic dysfunction.

II. CLINICAL PRESENTATION1. The most common presenting symptom of HF is dyspnea.2. Signs of HF include an accentuated S3, pulmonary rales, pleural

effusions, elevated jugular venous pressure, sustained abdominojugularreflux, lower extremity edema, Cheyne-Stokes respirations, a pulsatile

BOX 11-1CAUSES OF CARDIOMYOPATHYIschemicIdiopathic and familialHypertensive diseaseValvular diseaseTachycardia-induced cardiomyopathySleep apneaCarcinoid tumorInfiltrative disorders: amyloid, hemochromatosis, sarcoidConnective tissue disorders: systemic lupus erythematosus, polyarteritis nodosa,

rheumatoid arthritis, scleroderma, granulomatous disease, dermatomyositisEndocrine and metabolic: thyrotoxicosis, hypothyroidism, pheochromocytoma,

diabetes, myxedema, uremia, acromegaly, hypocalcemia, hypophosphatemia,porphyria, gout

Fabry’s diseaseGaucher’s diseaseGlycogen storage diseasesHematologic: polycythemia vera, sickle cell disease, leukemia, Loeffler’s diseaseInfectious and inflammatory: coxsackie B, human immunodeficiency virus,

Chagas’s disease, Lyme disease, adenovirus, cytomegalovirusMedications and toxins: alcohol, cocaine, catecholamines, anthracyclines

(doxorubicin), irradiation, cyclophosphamide, bleomycin, 5-fluorouracil, carbonmonoxide, lithium, chloroquine, arsenic, cobalt, antimony, snake venom,methysergide, lead, antidepressants, disopyramide, phosphorus poisoning, sulfadrug hypersensitivity

Muscular dystrophiesNutritional deficiencies: kwashiorkor, selenium, beriberi (thiamine), carnitine

deficiencyPericardial diseases (pseudocardiomyopathy)PeripartumRefsum’s diseaseTransplant rejectionWhipple’s disease

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liver, and ascites. Subtle signs and symptoms of fluid overload from HFinclude low-grade fevers, slight increases in abdominal girth, nausea,and anorexia.

3. Elevated jugular venous pressure and an audible S3 in patients with left ventricular dysfunction are associated with a higher risk ofhospitalizations for HF and death.3

4. Quantification of symptoms is based on the New York Heart Association(NYHA) classification scheme (Box 11-2).

5. Determining a patient’s hemodynamic profile is the most importantstep in evaluating a patient with suspected HF; the profile is based onevidence of congestion (wet vs. dry) or evidence of low perfusion (coldvs. warm). On the basis of this evaluation, patients can be placed intofour hemodynamic profiles, as shown in Table 11-1.

a. Evidence of congestion.(1) Symptoms of left-sided congestion: dyspnea at rest or early in

exertion, orthopnea, paroxysmal nocturnal dyspnea.(2) Symptoms of right-sided congestion: lower extremity edema,

abdominal fullness and bloating, and anorexia.(3) Physical signs: elevated jugular venous pressure, pulmonary rales,

loud P2, new or worsening S3, lower extremity edema, pulsatileliver. The most useful physical finding is elevation of the jugularvenous pressure both in the acute setting and longitudinally whentreating chronic HF.

b. Evidence of low perfusion.(1) Symptoms often are protean, including fatigue, somnolence, poor

concentration, and anorexia.(2) Physical signs include pallor, cool extremities, low volume pulses,

and a narrow pulse pressure.(3) A proportional pulse pressure ([systolic blood pressure (SBP) -

diastolic blood pressure (DBP)]/SBP) less than 0.25 is 91%

BOX 11-2NEW YORK HEART ASSOCIATION CLASSIFICATIONClass I: Symptoms of heart failure only at levels that would limit normal individualsClass II: Symptoms of heart failure with ordinary exertionClass III: Symptoms of heart failure on less than ordinary exertionClass IV: Symptoms of heart failure at rest

TABLE 11-1HEMODYNAMIC PROFILES IN HEART FAILURE

Congestion at Rest?No Yes

Low Perfusion at Rest? No Dry-warm Wet-warmYes Dry-cold Wet-cold

Modified from Nohria A, Lewis E, Stevenson L: JAMA 287:628, 2002.

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sensitive and 83% specific for a low output state (cardiac index of2.2 L/min/m2 or less).4

6. Evidence of systolic or diastolic dysfunction. Several features of thehistory and physical examination assist in determining whether HF iscaused primarily by systolic or diastolic dysfunction. Clinical findingscan be confirmed with the use of echocardiography.

a. Systolic HF. Evidence of cardiomegaly on chest radiograph, anterior Qwaves on electrocardiogram, left bundle branch block, diffuse softapical impulse, pulse greater than 100, and SBP less than 90.5

b. Nonsystolic HF. Hypertension during the HF episode with SBP greaterthan 160 mmHg or DBP greater than 100 mmHg. Other suggestivefeatures include an S4, female sex, history of hypertension,electrocardiographic evidence of left ventricular hypertrophy, tobaccouse, advanced age, and no prior history of myocardial infarction (MI).

c. Although the aforementioned clinical findings are suggestive, in practicesystolic and nonsystolic HF may be difficult to delineate because thereis significant overlap in their clinical presentations.6

III. DIAGNOSIS1. Laboratory evaluation should include a complete blood cell count,

comprehensive metabolic panel, coagulation studies, thyroid-stimulating hormone, creatine kinase with isozymes, and troponin.Measurement of brain natriuretic peptide is useful in addressing newonset HF and potentially in following patients with chronic HFlongitudinally, although such measurements should not be used inisolation but rather in combination with the history and physicalexamination.7,8 In patients with newly diagnosed HF of unclear origin,assays for ferritin, total iron-binding capacity, antinuclear antibody,rheumatoid factor, urinary metanephrines, human immunodeficiencyvirus antibody testing, and serum and urine protein electrophoresisshould be performed.

2. Electrocardiogram. An electrocardiogram should be obtained on allpatients with new or chronic HF to assess for signs of myocardialischemia, new conduction abnormalities, chamber enlargement,pericarditis, or right heart failure.

3. Chest radiography. Radiographic findings depend on the degree of HFand may include cardiomegaly, diffuse bilateral infiltrates extending from the hila, Kerley B lines, and pleural effusions. These findings maybe absent in patients with chronic HF with isolated right heart failure orthose who have adapted to elevated left ventricular filling pressures withenhanced pulmonary lymphatic clearance.

4. Echocardiography. All patients with a new-onset HF should undergotransthoracic echocardiography to assess systolic and diastolic function,valvular abnormalities, filling pressures, and pericardial disease.

5. Right and left heart catheterization. Coronary angiography is indicatedfor almost all patients with newly diagnosed HF to exclude ischemic

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heart disease if a readily apparent explanation does not exist. Rightheart catheterization (Swan-Ganz catheter) provides information aboutright- and left-sided filling pressures, pulmonary artery pressures,cardiac output, and systemic vascular resistance.

6. Endomyocardial biopsy. Some investigators have found right-sidedendomyocardial biopsy helpful as it may help facilitate the diagnosis in80% of patients with unexplained cardiomyopathy.9

7. Exercise testing. Exercise testing can be used to detect ischemic heartdisease and provides an estimate of functional capacity for riskstratification and prognosis in patients with known HF. Measurement of maximal oxygen uptake is an objective index of functional severityand the best index of prognosis, and it can be used to determine thenecessity and timing of cardiac transplantation in patients with chronicHF. The 6-minute walk test (distance the patient can walk in 6minutes) is a simpler test used in clinical practice that correlates withmaximal oxygen uptake.

IV. TREATMENTA. ACUTE HFA systematic search for precipitating causes must be performed in everypatient with new-onset or worsening HF (Box 11-3). Therapy should bedirected at the underlying cause (if identified and treatable) and standardHF therapy initiated on the basis of one of four clinical hemodynamicprofiles (Table 11-1).1. Treatment goals by hemodynamic profile.a. Wet and warm. This is the most common hemodynamic profile in HF.

These patients have congestion resulting from elevated filling pressuresand volume overload. Congestion can be relieved with intravenous loopdiuretics, and patients may benefit from intravenous or oral vasodilatorssuch as nitroglycerin. Positive inotropic agents often are unnecessaryand may be detrimental in patients who do not have evidence of lowperfusion.

BOX 11-3PRECIPITANTS OF ACUTE DECOMPENSATED HEART FAILUREMyocardial ischemiaHypertensionInfection (myocarditis)ArrhythmiaNoncompliance with medicationSodium and fluid indiscretion (dietary noncompliance)Excessive alcohol intakePulmonary embolismThyrotoxicosisHigh output (thyrotoxicosis, arteriovenous fistula, pregnancy, anemia)

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b. Wet and cold. Patients with congestion and critically limitedhypoperfusion often must be “warmed up” before they can be “driedout.”10 Perfusion may be improved through the use of vasodilatorsalone, although these patients may have therapy-limiting hypotensionnecessitating inotropic agents such as dopamine, milrinone, ordobutamine. In cases unresponsive to inotropic support, mechanicalcirculatory support with left ventricular assist devices or intraaorticballoon pump may be necessary as a lifesaving measure and a bridgeto heart transplantation.

c. Dry and warm. This hemodynamic profile represents compensated HF,and many patients with this form do not need inpatient management.Efforts should be aimed at maintaining stable volume status andpreventing disease progression, as outlined later in this chapter.

d. Dry and cold. This small subgroup of patients has a low cardiac output andevidence of poor perfusion but no clinical evidence of elevated fillingpressures. Patients may respond transiently to inotropes, but long-term usehas produced adverse effects. Careful management with ACE inhibitors,beta-blockers, and digoxin may lead to improvement in some patients,whereas others with unrecognized congestion may benefit from diuresis.

2. Pharmacologic agents in acute HF.a. Morphine is a m-opioid receptor agonist with both vascular and central

effects providing symptomatic relief in acute pulmonary edema throughvenodilation and a decreased perception of dyspnea. Potential sideeffects include hypotension, somnolence, and respiratory depression.

b. Diuretics.(1) Loop diuretics, such as furosemide, are the cornerstone of

therapy in acute decompensated HF. Furosemide produces acutevenodilation and increases sodium excretion, thereby reducingpreload and pulmonary vascular congestion.(a) In acute HF, patients who have been taking oral loop diuretics

should be switched to intravenous therapy because intestinalabsorption of oral agents may be limited by bowel wall edema.Patients with renal insufficiency may need higher dosages ofloop diuretics, and some may respond better to a continuousinfusion than intermittent doses.

(b) The starting intravenous dosage typically is half of the homeoral dosage. If there is not an adequate response (100 to 200 ml urine output) within 30 minutes, the dosage should bedoubled until the patient responds. Once an effective dosage isidentified, further diuresis can be accomplished by increasingthe frequency of administration.

(c) The diuretic effect of furosemide lasts 6 hours. Afterward, thekidneys are highly sodium avid, and diuretic efficacy will be lostif the patient is not maintained on a low-sodium diet as well.

(d) Markers of adequate diuresis include resolution of dyspnea,decrease in jugular venous pressure, decrease in intensity of S3,

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elevation of serum creatinine level, and attainment of dryweight. Side effects of loop diuretics include hypokalemia,hypomagnesemia, hyponatremia or hypernatremia, volumedepletion, renal failure, and reversible ototoxicity.

(2) Adding a thiazide diuretic such as chlorothiazide can potentiate theeffect of loop diuretics by preventing compensatory distal tubularreabsorption of sodium. Thiazide diuretics should be givenapproximately 30 minutes before a loop diuretic is administered.11

c. Nesiritide, or recombinant B-type natriuretic peptide, is a natriureticpeptide with potent vasodilator and natriuretic effects that reducepulmonary capillary wedge pressure, right atrial pressure, and systemicvascular resistance and increase cardiac index.12 Nesiritide is associatedwith a lower incidence of arrhythmias than that of other inotropes andmay be particularly useful in patients with decompensated HF andtachyarrhythmias. The most common adverse effect of nesiritide ishypotension.

d. Vasodilators.(1) ACE inhibitors are started at low dosages with short-acting agents

such as captopril and titrated to the maximum tolerated dosage.Blood pressure response, symptoms, and serum potassium andcreatinine levels should be monitored closely. Once short-actingagents are tolerated, patients should be transitioned to long-actingagents. About 10% to 30% of patients with advanced HF cannottolerate ACE inhibitors because of hypotension or renal dysfunction.8

(2) Organic nitrates such as nitroglycerin are vasodilators (particularlyof the systemic veins), resulting in decreased preload. Nitrates havea role in the management of acute pulmonary edema and HF inthe setting of hypertension or angina. Contraindications includeconcurrent sildenafil use and severe aortic stenosis.

(3) Hydralazine is a potent short-acting arterial vasodilator that can beused alone or in combination with nitrates for rapid afterloadreduction. It is often considered as an alternative to ACE inhibitorsand angiotensin II receptor blockers (ARBs) in patients with acuterenal failure and other conditions in which ACE inhibitors arecontraindicated.

(4) Nitroprusside is a potent intravenous arterial vasodilator that maybe warranted if further vasodilation and afterload reduction arenecessary. Adverse effects include thiocyanate toxicity, particularlyin patients with hepatic or renal dysfunction, and coronary stealphenomenon in patients with ischemic heart disease.

e. Beta-blockers should be used with caution in acute HF exacerbations.Patients naive to beta-blockade should be euvolemic and tolerating astable dosage of ACE inhibitors before beginning beta-blocker therapy.Patients already on beta-blockers may have to have their dosagetemporarily reduced, but beta-blockers should not be withdrawn unlesshypotension or cardiogenic shock is present.

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f. Inotropes may be used for the temporary treatment of diuretic-refractoryacute HF (i.e., cold and wet) and as a bridge to definitive treatmentsuch as revascularization or cardiac transplantation. Inotropes may alsobe appropriate as a palliative measure in patients with end-stage HF.The routine use of inotropes is not indicated in either acute or chronicHF.13

(1) Dopamine is an endogenous catecholamine that has distinctcardiovascular effects at escalating dosages: Low-dose dopamine (1 to 3 mg/kg/min) acts through dopaminergic receptors, leading toincreased renal blood flow and natriuresis; intermediate dosages (2 to 10 mg/kg/min) result in predominant beta-adrenergic receptorstimulation, increasing cardiac output by augmenting contractilityand heart rate; higher dosages (10 to 20 mg/kg/min) result inincreased afterload through alpha-adrenergic stimulation, whichmay be detrimental in HF. Dopamine should be used primarily tostabilize hypotensive patients. Tachycardia may be an undesirableside effect, particularly in those with ischemic heart disease ordiastolic dysfunction who depend on filling time. Low-dosedopamine in critically ill patients has not been shown to improvediuresis and does not provide renal protection in patients with renaldysfunction.14

(2) Dobutamine is a beta-adrenergic agonist with a predominanthemodynamic effect of direct inotropic stimulation with reflexarterial vasodilation, resulting in afterload reduction and increasedcardiac output. Side effects include hypotension, ventriculararrhythmias, and potentially worsening ischemic heart disease byincreasing myocardial oxygen demand.

(3) Milrinone, a phosphodiesterase inhibitor, increases contractility and produces vasodilation. As with dobutamine, hypotension andarrhythmias may occur.

3. Response to therapy. Once treatment has begun, careful attentionshould be paid to daily weights, urine output, jugular venous pressure,and pulse pressure. Use of Swan-Ganz catheters in patients with acuteHF exacerbations who do not otherwise have an indication for a Swan-Ganz catheter is safe but does not alter length of stay, rehospitalizationrates, or mortality.15

B. CHRONIC HF1. Systolic HF.Staging: HF is a continuum of stages progressing from asymptomatic toadvanced disease (Fig. 11-1).

Stage A: Patients at high risk for left ventricular dysfunction. The leading risk factor for HF is ischemic heart disease, accounting for approximately 60% of new cases.16 Other risk factors includehypertension, diabetes mellitus, familial history, and presence ofcardiotoxins such as excessive alcohol, radiation, and chemotherapy.Interventions include controlling hypertension17 and hyperlipidemia;

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Stage B:Structural heart diseaseand No HF symptoms

Stage C:Structural heart disease andPrior or current HF symptoms

Stage D:Advanced HFRefractory to maximum therapy

Patients with:HypertensionDiabetesExposure to cardiotoxinsFamily history of cardiomyopathy

Patients with:Previous MILeft ventricular hypertrophyLeft ventricular systolic dysfunctionAsymptomatic valvular disease

Patients with:Known structural heart diseaseShortness of breath and fatigue, reduced exercise tolerance due to left ventricular systolic dysfunction

Patients with:Marked symptoms at rest despite maximal medical therapy

Structural heart disease

Development of symptoms

Refractory symptoms

Stage A:At high risk for HF:No structural heart disease andNo HF symptoms

Therapy:Treat hypertensionTreat lipid disordersStop smokingAvoid alcoholACE inhibitors in patients with vascular disease, diabetes, or hypertension and cardiovascular risk factors

Therapy:Stage A measures andACE inhibitors if history of MI or reduced EFb-Blockers if history of MI or reduced EFValve surgery if indicated

Therapy:Stage A measures andDiureticsACE inhibitorsb-BlockersDigoxinSalt restrictionSpironolactone

Therapy:Stage A, B, and CmeasuresandMechanical assist devicesHeart transplantationContinuous intravenousinotropic infusionsfor palliationHospice care

FIG. 11-1

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• • • •

•

•

•

•

•

• ••

••

•

•

•

••

•

• •

• •

•

•

••

•

Stages in the evolution of heart failure and recommended therapy by stage.9 ACE,angiotensin-converting enzyme; EF, ejection fraction; HF, heart failure; MI, myocardialinfarction.

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discouraging smoking, excessive alcohol intake, and illicit drug use; andencouraging exercise and weight loss. ACE inhibitors are indicated forpatients with atherosclerotic vascular disease (MI, cerebrovascularaccident, peripheral vascular disease) or diabetes with associated riskfactors.18

Stage B: Patients with structural heart disease in whom symptomshave not yet developed. Asymptomatic patients with a prior MI, evidenceof left ventricular hypertrophy, left ventricular dysfunction, or valvulardisease are at very high risk for HF. In addition to the recommendationsfor stage A, all patients with systolic dysfunction, regardless of symptoms,should receive ACE inhibitors. ACE inhibitors and beta-blockers areindicated for patients with a history of MI regardless of the ejectionfraction. Beta-blockers may be used for patients with asymptomaticsystolic dysfunction, although the evidence is not as strong as it is forsymptomatic patients. Valvular repair or replacement should be performedaccording to published guidelines (see Chapter 12).19

Stage C: Patients with left ventricular dysfunction with current orprior symptoms. Readmission for HF occurs at a high rate (30% to 50%)in the 6 months after discharge. A number of criteria should be met before discharge, including transition to oral medications for 24 hours,achievement of dry weight, stable or improving renal function, andambulation with decreased dyspnea and without symptomatichypotension. During hospitalization patients should receive educationabout sodium and fluid restriction and recommendations for exercise.Patients should monitor their weight at home and may benefit from asliding scale outpatient diuretic regimen based on their daily weight.Vaccination for pneumococcal infection and influenza is recommended.Use of nonsteroidal antiinflammatory drugs for patients with advanced HF should be avoided because it may lead to fluid retention and renaldysfunction. Recommendations listed under stage A and B apply as well.

Stage D: Patients with refractory end-stage HF. Recommendationsinclude meticulous control of fluid retention with diuretics. ACE inhibitorsand beta-blockers are beneficial, but these patients are at particular risk of developing hypotension and renal failure with ACE inhibitors andworsening HF with beta-blockers. Cardiac transplantation should beconsidered in eligible patients. Left ventricular assist devices providehemodynamic support for patients awaiting heart transplantation and may be beneficial even for patients who are not candidates for hearttransplantation.20 Continuous intravenous inotropic infusions and hospicemay be used as palliative measures in patients with end-stage HF.2. Pharmacologic agents in chronic HF.a. ACE inhibitors are indicated for all patients with systolic dysfunction as

they improve survival, relieve symptoms, prevent hospitalization, andhalt the progression of left ventricular remodeling.21,22 They may haveadded benefit at higher dosages,23 and attempts should be made toachieve target dosages reported in major clinical trials (lisinopril 20 to

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40 mg/day, enalapril 10 mg twice a day, or captopril 50 mg threetimes a day). The benefit of ACE inhibitors in HF is independent oftheir blood pressure–lowering effect. Cough and angioedema areadverse effects most commonly associated with ACE inhibitors.Contraindications include symptomatic hypotension, acute renal failure,bilateral renal artery stenosis, hyperkalemia, and pregnancy.

b. ARBs. When patients are intolerant of ACE inhibitors, use of an ARBresults in a significant reduction in mortality and HF hospitalizations.24

As with ACE inhibitors, however, ARBs should not be used in thepresence of acute renal failure or hyperkalemia and may producesymptomatic hypotension. Studies directly comparing ARBs and ACEinhibitors have shown no greater survival with use of ARBs.25,26

Addition of an ARB to a regimen with an ACE inhibitor shows a trendtoward improvement in mortality and reduced hospitalizations.27 Giventhe greater experience with ACE inhibitors, they should be used as first-line agents, and ARBs should be reserved for patients who cannottolerate ACE inhibitors.

c. Nitrates and hydralazine. Isosorbide dinitrate (40 mg four times a day)combined with hydralazine (75 mg four times a day) has been shownto improve survival in chronic HF.28 Although inferior to ACE inhibitors,this combination should be considered for patients who cannot tolerateACE inhibitors and ARBs.29 A “nitrate-free” interval should be allowed toprevent the development of nitrate tolerance in patients on long-termtherapy. This combination may be especially useful in African Americanpatients with HF.30

d. Beta-blockers. Several beta-blockers have been shown to reducemortality in patients with symptomatic HF and systolic dysfunction,including metoprolol, carvedilol, and bisoprolol.31,32 All stable,euvolemic patients with NYHA class II to IV HF resulting from leftventricular dysfunction should receive a beta-blocker unless they cannottolerate beta-blockers or have a contraindication. Usually an ACEinhibitor is titrated first, and the beta-blocker is added sequentially inthe outpatient setting. Metoprolol extended release (metoprololsuccinate) can be initiated at 25 mg per os (PO) daily (12.5 mg POdaily in NYHA class IV) and titrated slowly (monthly) to a maximumdosage of 200 PO daily. Carvedilol is begun at 3.125 mg PO twicedaily and titrated (every 2 weeks) to a maximum dosage of 25 to 50mg PO twice daily. Bisoprolol is begun at a dosage of 1.25 PO daily and titrated to 10 mg PO daily. Carvedilol has been shown tohave a survival advantage over short-acting metoprolol33 and betterejection fraction compared with extended-release metoprolol in a meta-analysis.34 Contraindications to beta-blockade include acutedecompensated HF, symptomatic bradycardia, advanced heart block,and severe bronchospastic disease. Although many patients takeatenolol, no studies evaluating the use of atenolol in chronic HF havebeen presented.

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e. Diuretics.(1) Loop diuretics. In addition to their role in acute management of

HF, loop diuretics have a central role in long-term management toattenuate progressive volume overload caused by compensatorysodium avidity. Diuretics are indicated for patients withsymptomatic HF even after they have been rendered free of edemaand generally are necessary indefinitely. Serum electrolytes should be monitored closely given the concern for increased risk ofarrhythmic death in patients with HF taking non–potassium-sparing diuretics.35

(2) Aldosterone antagonism. Aldosterone blockade provides a diureticeffect and modulates the harmful effects of aldosterone on theheart. Spironolactone, a potassium-sparing diuretic, has beenshown to decrease both mortality and rehospitalization by one thirdin patients with primarily NYHA class III to IV HF.36 Spironolactoneis given as a once-daily dose of 25 mg to those without renalinsufficiency or hyperkalemia. Patients should have stable serumcreatinine levels less than 2.5 mg/dl and serum potassium lessthan 5 mmol/L, should undergo frequent electrolyte monitoring for hyperkalemia, and should not receive daily potassiumsupplementation.37 Gynecomastia, breast pain, menstrualirregularities, and impotence are troubling side effects in about10% of patients. Eplerenone is another alternative shown to reduceall-cause mortality in patients with reduced left ventricular ejectionfraction after an MI.38

f. Digoxin. Digoxin is a glycoside shown to improve symptoms andprevent hospitalization in patients with systolic dysfunction.39 It isindicated for patients with HF symptoms despite optimal therapy withACE inhibitors and diuretics or for patients with coexisting atrialfibrillation. Toxic effects are more likely to occur in patients with renal insufficiency, electrolyte abnormalities, advanced age, andcoadministration of other antiarrhythmic drugs (e.g., amiodarone,quinidine, verapamil, propafenone). Toxic manifestations includeconfusion, nonspecific gastrointestinal complaints, vision and colordisturbances, and arrhythmia.

g. Warfarin. Anticoagulation with warfarin is warranted for patients withconcomitant atrial fibrillation, visible thrombus on echocardiogram, or aprevious cardioembolic event.40 Although many consider anticoagulationfor patients with a very low ejection fraction (< 20%), recent data fromthe Warfarin and Antiplatelet Therapy in Heart Failure (WATCH) trialsuggest no short-term (23 months) benefit in reducing the incidence ofnonfatal stroke, death, or nonfatal MI in patients with an ejectionfraction of 35% or less randomized to aspirin, clopidogrel, orCoumadin.41

h. Exercise. A prescription for exercise may improve functional capacityand quality of life and prevent death from cardiovascular disease.42

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i. Maintenance of sinus rhythm. Patients with HF benefit from normalsinus rhythm. Achieving this goal can be difficult with antiarrhythmicdrugs in HF given potential drug interactions. Recent literature hasshown an improvement in ejection fraction, symptoms, exercisecapacity, and quality of life when patients are maintained in sinusrhythm by means of catheter ablation.43

3. Nonsystolic HF.Acute exacerbations of nonsystolic HF generally are treated in a similarfashion as acute exacerbations of systolic HF. Few large trials haveevaluated long-term treatment for nonsystolic HF. Based on thepathophysiology of diastolic dysfunction, four principles may be used toguide management.9,44

a. Control of blood pressure. Beta-blockers, ACE inhibitors, ARBs, andcalcium channel blockers may be used to control SBP and DBPaccording to published guidelines. In the largest treatment trial fornonsystolic HF, the ARB candesartan, when added to traditionalmedical therapy, was associated with fewer hospitalizations for HF.45

b. Control of tachycardia. Patients with atrial fibrillation need rate controland may benefit from an attempt at cardioversion to optimize leftventricular filling.

c. Control of pulmonary congestion and edema. Patients may have ralesand evidence of volume overload (elevated neck veins and peripheraledema). Loop diuretics such as furosemide decrease filling pressuresand relieve pulmonary congestion. Care must be taken with diuresisbecause patients with diastolic HF are sensitive to preload reduction,and hypotension or prerenal azotemia may develop.

d. Assessment and control of ischemia. Revascularization should beconsidered for patients with evidence of ischemia.

4. Device therapy for HF. Patients with HF and reduced left ventricularfunction are at a higher risk for sudden cardiac death caused byventricular arrhythmias. The Multicenter Automatic DefibrillatorImplantation Trial II (MADIT II) showed a lower all-cause mortality forthe use of ICDs as primary prevention in patients with a left ventricularejection fraction less than 30% in cardiomyopathy of ischemic origin.46

ICDs also provide a mortality benefit when used in patients withcardiomyopathy of nonischemic origin.47 Combining ICD therapy with abiventricular pacemaker, known as cardiac resynchronization therapy,has also been shown to reduce all-cause mortality and hospitalizationsin patients with ischemic or nonischemic cardiomyopathies.48 Giventhese trials, ICDs with and without cardiac resynchronization therapyhave become additional tools in the management of HF (see Chapter15).

PEARLS AND PITFALLS� Patients already on beta-blocker therapy with HF exacerbations should

remain on their current dosage (hemodynamics permitting) withoutescalation, whereas those who are naive to beta-blockers should not

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receive beta-blockade until clinically euvolemic and on a stable ACEinhibitor dosage.

� Accurate bedside determination of jugular venous pressure is crucial tosuccessful management of HF.

� Frequent outpatient evaluation in chronic HF management helps toreduce hospitalizations.

� Care should be taken with the use of nonsteroidal antiinflammatorydrugs, metformin, thiazolidinediones, sildenafil, and antiarrhythmic drugsbecause these medications may precipitate exacerbations of HF.

� Daily weight measurement at home allows patients to titrate diuretics toa goal weight.

� Atrial fibrillation can be deleterious to patients with systolic andnonsystolic HF.

� Patients who need positive inotropic support with dobutamine ordopamine may not receive the full benefit of these agents if on beta-blockers.

REFERENCES1. American Heart Association: Heart disease and stroke statistics: 2004 update,

Dallas, 2003, American Heart Association. C2. Vasan RS, Benjamin EJ, Levy D: Prevalence, clinical features and prognosis of

diastolic heart failure: an epidemiologic perspective, J Am Coll Cardiol 26:1565,1995. B

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