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Chapter 1: Chronic Heart Failure

Jo E. Rodgers; Brent N. Reed

FOUNDATION OVERVIEW
Heart failure (HF) is a syndrome of reduced cardiac output (CO) resulting from impaired ventricular ejection, impaired filling, or components of both.
HF with reduced ejection fraction (HFrEF) was formerly known as systolic dysfunction, whereas HF with preserved ejection fraction (HFpEF) was
formerly known as diastolic dysfunction. Although half of HF cases are due to HFpEF, the majority of clinical studies enroll patients with HFrEF. Chronic
HFrEF management includes lifestyle modifications, medications, and implantable devices. However, there are few therapeutic approaches for HFpEF
management.

Etiology and Pathophysiology

The etiology of HF is often classified as being ischemic or nonischemic. Ischemic causes are more common and may result from a sudden event such as
a myocardial infarction (MI) or from longstanding coronary artery disease. Nonischemic etiologies include uncontrolled hypertension (HTN), viral
diseases, sarcoidosis, peripartum cardiomyopathy, uncorrected valvular heart disease, alcohol, or thyroid disease.

The pathophysiology of HFrEF is characterized by compensatory mechanisms intended to maintain systemic perfusion in response to a decline in CO
(Figure 1­1). The sympathetic nervous system (SNS) and renin angiotensin aldosterone system (RAAS) are primarily responsible for this compensatory
response (although vasopressin and nitric oxide are also involved). Norepinephrine is released from the SNS in an effort to maintain CO by increasing
contractility and heart rate (HR). Renal hypoperfusion results in RAAS activation with a resultant rise in serum angiotensin II and aldosterone
concentrations. As potent vasoconstrictors, norepinephrine and angiotensin II compromise CO by increasing afterload while aldosterone increases
preload via enhanced sodium and fluid retention. Increased preload and afterload initially improve organ perfusion but ultimately result in a decline in
CO as a consequence of ventricular remodeling and hypertrophy. This cycle is propagated as further declines in CO produce additional release of
compensatory neurohormones.

FIGURE 1­1

Pharmacotherapy of heart failure.

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The pathophysiology 2:36 Ahas
of HFpEF Your
not IP is 202.28.119.100
been well elucidated, although impaired diastolic function is thought to play a major role. Therapies aimed at
Chapter
disrupting the neurohormonal systems responsibleBrent
1: Chronic Heart Failure, Jo E. Rodgers; N. Reed
for HFrEF have not substantially improved outcomes in HFpEF, suggesting different
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pathophysiologic features are involved.
compensatory neurohormones.
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FIGURE 1­1
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Pharmacotherapy of heart failure.

The pathophysiology of HFpEF has not been well elucidated, although impaired diastolic function is thought to play a major role. Therapies aimed at
disrupting the neurohormonal systems responsible for HFrEF have not substantially improved outcomes in HFpEF, suggesting different
pathophysiologic features are involved.

Clinical Presentation

HF patients present with signs and symptoms of volume overload, low CO, or both. Patients with volume overload present with signs and symptoms of
pulmonary congestion (eg, dyspnea, orthopnea, crackles on auscultation) or peripheral congestion (eg, ascites, jugular venous distension, lower
extremity edema). Weight gain can be a helpful marker of volume status for patients to self­monitor, as it often precedes signs and symptoms. Signs
and symptoms of low CO are more challenging to identify and may be subjective. Vague symptoms such as fatigue or nausea and vomiting are
common. Worsening renal function is a common objective measure of low CO, whereas exercise intolerance and early satiety may be present with
either volume overload or low CO.

Diagnosis

HF is a clinical diagnosis and no single test establishes its presence or absence. The most frequent clinical findings in HF are related to decreased
exercise tolerance or fluid retention. Decreased exercise tolerance typically presents as dyspnea or fatigue on exertion. Fluid retention results in
orthopnea, crackles, elevated jugular venous pressure, dependent edema, and radiographic findings of cardiomegaly, pulmonary edema, and pleural
effusion.

A comprehensive patient history should be obtained to elucidate causes of HF. Both MI and HTN are common causes; thus, cardiovascular risk factors
should be addressed. Detailed medication histories should be completed to ensure dietary and medication adherence and avoidance of substance
abuse. Presence of medications known to exacerbate fluid retention (eg, nonsteroidal anti­inflammatory drugs [NSAIDs]), alter left ventricular function
(eg, certain antineoplastic agents), and those with negative inotropic effects (eg, nondihydropyridine calcium channel blockers) should also be
assessed (Table 1­1). Measurement of B­type natriuretic peptide (BNP) may be helpful in differentiating HF from other disease states associated with
similar symptoms. An echocardiogram to evaluate ventricular function should be performed to determine etiology and severity of HF. An ejection
fraction (EF) of less than 40% is considered the threshold for HFrEF classification.

TABLE 1­1
Medications That May Precipitate or Exacerbate Heart Failure

Negative Inotropic Effect

Antiarrhythmics (eg, disopyramide, dronedarone, flecainide, propafenone)

β­Blockers (eg, propranolol, metoprolol, atenolol)

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verapamil, diltiazem)
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Itraconazole
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Negative Inotropic Effect
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Antiarrhythmics (eg, disopyramide, dronedarone, flecainide, propafenone)

β­Blockers (eg, propranolol, metoprolol, atenolol)

Nondihydropyridine calcium channel blockers (eg, verapamil, diltiazem)

Itraconazole

Cardiotoxic

Doxorubicin

Daunorubicin

Epirubicin

Cyclophosphamide

Trastuzumab

Imatinib

Ethanol

Amphetamines (eg, cocaine, methamphetamine)

Sodium and Water Retention

Nonsteroidal anti­inflammatory drugs

Thiazolidinediones (eg, rosiglitazone)

Glucocorticoids

Androgens and estrogens

Salicylates (high dose)

Sodium­containing drugs (eg, piperacillin sodium)

Uncertain mechanism

Infliximab

Etanercept

Dipeptidyl peptidase­4 inhibitors (eg, sitagliptin)

Bezlotoxumab

Classification/Staging

HF severity is classified according to disease state progression (American College of Cardiology/American Heart Association [ACC/AHA]) or functional
class (New York
Downloaded Heart Association
2022­2­10 [NYHA]).
2:36 A Your IP isThe ACC/AHA system stages patients based on risk for developing HF (stage A), having asymptomatic
202.28.119.100
structural1:heart
Chapter disease
Chronic Heart(stage B), HF
Failure, Josigns and symptoms
E. Rodgers; (stage
Brent N. ReedC), or end­stage disease despite maximal medical therapy (stage D). The NYHA Page 3 / 11
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and ability to perform activities of daily living. Patients are classified as
having no symptoms limiting activity (class I), symptoms with mild or moderate physical activity (class II and III, respectively), or symptoms at rest (class
IV). A patient may shift between NYHA functional classes as HF status improves or declines, but cannot regress from an advanced ACC/AHA stage.
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Classification/Staging

HF severity is classified according to disease state progression (American College of Cardiology/American Heart Association [ACC/AHA]) or functional
class (New York Heart Association [NYHA]). The ACC/AHA system stages patients based on risk for developing HF (stage A), having asymptomatic
structural heart disease (stage B), HF signs and symptoms (stage C), or end­stage disease despite maximal medical therapy (stage D). The NYHA
functional classification system is a subjective measure of exercise tolerance and ability to perform activities of daily living. Patients are classified as
having no symptoms limiting activity (class I), symptoms with mild or moderate physical activity (class II and III, respectively), or symptoms at rest (class
IV). A patient may shift between NYHA functional classes as HF status improves or declines, but cannot regress from an advanced ACC/AHA stage.

PREVENTION
General Considerations

Patients without structural heart disease (ACC/AHA stage A) should have comorbidities managed according to established practice guidelines (eg, HTN,
dyslipidemia). Patients with asymptomatic left ventricular dysfunction (stage B) are at a high risk for developing HF and should receive an angiotensin­
converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and a β­blocker to reduce mortality and risk of HF progression. Because most
of the studies evaluating these therapies have enrolled patients with symptomatic HF, they are discussed in detail in the sections to follow.

TREATMENT
General Overview and Goals of Treatment

The goals of HF management are to maximize quality of life (QOL), minimize symptoms, prevent hospitalizations, slow disease progression, and
prolong survival. It is important to identify and treat reversible, underlying causes of HF. Patients should be educated on fluid and sodium restrictions
and encouraged to weigh themselves daily to detect changes in volume status. Drug therapy is the cornerstone of treatment and focuses on inhibiting
the neurohormonal cascade described in Table 1­2 and Figure 1­1 for mechanism, dosing, and monitoring of neurohormonal blocking agents.

TABLE 1­2
Dosing and Monitoring for Select Neurohormonal Blocking Agents

Initial Oral Target or Maximum Oral

Drug Monitoring, Adverse Effects, and Contraindications
Dose Dose

ACE Inhibitors

Captopril 6.25 mg three 50 mg three times daily Monitoring:

times daily BP

Enalapril 2.5 mg twice 10­20 mg twice daily K+, BUN, SCr at baseline, 2 weeks, and after dose titration
daily Adverse effects: Hyperkalemia, hypotension, renal dysfunction, cough,
angioedema, rash (captopril)
Fosinopril 5­10 mg once 40 mg once daily Contraindications:
daily Angioedema, pregnancy

Lisinopril 2.5­5 mg once 20­40 mg once daily

daily

Perindopril 2 mg once daily 8­16 mg once daily

Quinapril 5 mg twice 20 mg twice daily

daily

Ramipril 1.25­2.5 mg 10 mg once daily

once daily
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Chapter 1: Chronic Heart Failure,
Trandolapril Jo E.
1 mg once Rodgers;
daily Brent
4 mg once N. Reed
daily Page 4 / 11
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ARBs
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daily

Ramipril 1.25­2.5 mg 10 mg once daily

once daily

Trandolapril 1 mg once daily 4 mg once daily

ARBs

Candesartan 4­8 mg once 32 mg once daily Monitoring:

daily BP

Losartan 25­50 mg once 100­150 mg once daily K+, BUN, SCr at baseline, 2 weeks, and after dose titration
daily

Valsartan 20­40 mg twice 160 mg twice daily Adverse effects: Hyperkalemia, hypotension, renal dysfunction
daily Contraindications:
Angioedema, pregnancy

Aldosterone Antagonists

Spironolactone 12.5­25 mg 25 mg once daily Monitoring:

once daily BP

Eplerenone 25 mg once 50 mg once daily K+ and SCr at baseline, at 1 week of initiation and then monthly for first 3 mo
daily Adverse effects: Hyperkalemia, renal dysfunction, gynecomastia or breast
tenderness (primarily spironolactone), menstrual changes, hirsutism
Contraindications:
Anuria, hyperkalemia
Other: NIOSH list of hazardous medications (spironolactone)

β­Blockers

Bisoprolol 1.25 mg once 10 mg once daily Monitoring:

daily BP, HR at baseline and after each dose titration, ECG

Carvedilol 3.125 mg twice 25 mg twice daily (50 mg

daily twice daily for patients >85
kg)

Metoprolol succinate 12.5­25 mg 200 mg once daily Adverse effects:

once daily Worsening HF symptoms (edema, SOB, fatigue), depression, sexual
dysfunction, bradycardia, hypotension
Contraindications:
Cardiogenic shock, asthma with active bronchospasm, severe bradycardia,
second­ or third­degree heart block
Other: metoprolol succinate tablet is scored and may be split but not crushed
or chewed

Miscellaneous Agents

Sacubitril/valsartan 24/26 mg­ 97/103 mg twice daily Monitoring:

49/51 mg twice BP
daily K+, BUN, SCr at baseline, 2 wk, and after dose titration
Adverse effects: Hyperkalemia, hypotension, renal dysfunction, angioedema
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• Notice • Accessibility
pregnancy
Other: Do not administer within 36 h of ACE inhibitor
 Miscellaneous Agents
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Sacubitril/valsartan 24/26 mg­ 97/103 mg twice daily Monitoring: Access Provided by:

49/51 mg twice BP
daily K+, BUN, SCr at baseline, 2 wk, and after dose titration
Adverse effects: Hyperkalemia, hypotension, renal dysfunction, angioedema
Contraindications:
Angioedema, pregnancy
Other: Do not administer within 36 h of ACE inhibitor

Isosorbide 20/37.5 mg 40/75 mg three times daily Monitoring:

dinitrate/hydralazine three times BP, HR
daily Adverse effects:
Headache, flushing, hypotension, dizziness
Contraindications:
Concomitant use of PDE­5 inhibitors

Ivabradine 2.5­5 mg twice 7.5 mg twice daily Monitoring:

daily BP, HR baseline and after each dose titration, ECG
Adverse effects: Bradycardia, atrial fibrillation, visual disturbances
Contraindications:
Clinically significant bradycardia, sick sinus syndrome or atrioventricular
block, concomitant use of strong CYP3A4 inhibitors

Digoxin 125­250 mcg Target SDC of 0.5­0.9 ng/mL Monitoring:

once daily HR, ECG, SDC
Adverse effects:
Neurologic changes, visual disturbances, nausea/vomiting, arrhythmias
Contraindications:
Unstable renal function

Abbreviations: ACE, angiotensin­converting enzyme; ARBs, angiotensin receptor blockers; BP, blood pressure; BUN, blood urea nitrogen; CBC, complete blood cell
count; ECG, electrocardiogram; HF, heart failure; HR, heart rate; K+, potassium; NIOSH, National Institute for Occupational Safety and Health; PDE­5,
phosphodiesterase­5; SCr, serum creatinine; SDC, serum digoxin concentrations; SOB, shortness of breath.

Pharmacologic Therapy

Loop Diuretics

Sodium and fluid retention is common in HF, and loop diuretics are frequently used to assist in fluid elimination. Loop diuretics (furosemide,
bumetanide, torsemide, and ethacrynic acid) block sodium reabsorption in the ascending loop of Henle. Loop diuretics provide symptomatic relief of
volume overload, improve exercise tolerance, and prevent hospitalization; however, they do not confer a mortality benefit. Patients can develop
resistance to loop diuretics requiring escalation of dose or addition of thiazide diuretics. For patients who are refractory to the most commonly used
loop diuretic, furosemide at maximally tolerated doses, consider switching to bumetanide or torsemide (oral furosemide 40 mg = bumetanide 1 mg =
torsemide 20 mg) for more reliabile bioavailability, or adding a thiazide­type diuretic. Common adverse effects include hypokalemia,
hypomagnesemia, hypotension, and renal dysfunction. To avoid nocturia, twice­daily dosing with furosemide and bumetanide should be scheduled
approximately 6 hours apart in the morning and afternoon. Torsemide should only be dosed once daily. Weight should be monitored daily to prevent
overdiuresis. Signs and symptoms of overdiuresis resulting in dehydration include orthostatic hypotension and an elevated BUN/serum creatinine
(SCr) ratio.

Angiotensin­Converting Enzyme Inhibitors

ACE inhibitors prevent the conversion of angiotensin I to angiotensin II and have demonstrated reductions in mortality, HF progression,
hospitalizations, and improvement in symptoms. Unless contraindicated, ACE inhibitors are recommended for all patients with a reduced EF,
regardless of symptoms. As tolerated, ACE inhibitors should be titrated to target doses achieved in clinical trials (see Table 1­2), although this is not
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Chronic addition of β­blocker
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Jo E. Rodgers; Patients should be monitored for hypotension, hyperkalemia, renal dysfunction, cough,
N. Reed and6 / 11
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angioedema. Absolute contraindications include a history of angioedema, bilateral renal artery
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Angiotensin Receptor Blockers

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ACE inhibitors prevent the conversion of angiotensin I to angiotensin II and have demonstrated reductions in mortality, HF progression,
hospitalizations, and improvement in symptoms. Unless contraindicated, ACE inhibitors are recommended for all patients with a reduced EF,
regardless of symptoms. As tolerated, ACE inhibitors should be titrated to target doses achieved in clinical trials (see Table 1­2), although this is not
required prior to the addition of β­blocker therapy. Patients should be monitored for hypotension, hyperkalemia, renal dysfunction, cough, and
angioedema. Absolute contraindications include a history of angioedema, bilateral renal artery stenosis, and pregnancy (black box warning).

Angiotensin Receptor Blockers

ARBs competitively inhibit angiotensin II receptors. ACE inhibitors remain first­line therapy because comparable improvements with ARBs have not
been observed across all HF outcomes. ARBs may be considered in patients who are intolerant of ACE inhibitors, such as those who experience cough
and angioedema, as these adverse effects are thought to be due to reduced bradykinin metabolism. Patients who develop renal dysfunction,
hyperkalemia, or hypotension with an ACE inhibitor are likely to experience these adverse effects with an ARB. In addition, ARBs have the same
absolute contraindications as ACE inhibitors (see Table 1­2).

β­Adrenergic Blockers

Historically, β­blockers were not used to manage HF because of their negative inotropic effects. However, long­term inhibition of the SNS with β­
blocker therapy is associated with improvements in mortality, even in advanced disease. These benefits do not appear to be class­related, as only
bisoprolol, carvedilol, and metoprolol succinate (controlled­ or extended­release) have demonstrated mortality improvements in HF. β­Blockers
should be started at low doses once patients are euvolemic and titrated as tolerated to the doses achieved in clinical trials (see Table 1­2). When
adjusted under optimal conditions, symptoms may transiently worsen until a new equilibrium is established. Patients with volume overload should not
have doses increased until excess fluid is removed. Patients should be monitored for hypotension, bradycardia, fluid retention, and fatigue. Absolute
contraindications for β­blocker therapy include cardiogenic shock, asthma with active bronchospasm, symptomatic hypotension or bradycardia, and
complete heart block. Comorbidities such as diabetes mellitus, chronic obstructive pulmonary disease, asthma without bronchospasm, and peripheral
vascular disease should not be considered absolute contraindications to β­blocker therapy. A β1­selective agent (eg, metoprolol succinate or
bisoprolol) is preferred in patients with asthma.

Neprilysin Inhibitor/Angiotensin Receptor Blocker

Neprilysin degrades natriuretic peptides and other circulating mediators responsible for counteracting the compensatory neurohormonal response in
patients with HF. A combination of the neprilysin inhibitor sacubitril and the ARB valsartan demonstrated reductions in mortality, hospitalizations, and
HF symptoms compared to an ACE inhibitor. Thus, in patients who remain symptomatic despite receiving an ACE inhibitor or ARB and a β­blocker,
replacement of the ACE inhibitor or ARB with sacubitril/valsartan is recommended. Patients previously receiving an ACE inhibitor should have therapy
withdrawn for at least 36 hours prior to initiating sacubitril/valsartan due to an increased risk of angioedema with overlapping therapy. Monitoring
parameters are similar to those for ACE inhibitors (see Table 1­2). Absolute contraindications include a history of angioedema and pregnancy.

Aldosterone Receptor Antagonists

Although ACE inhibitors and ARBs reduce the amount of aldosterone release in the short­term, further suppression of aldosterone can be achieved
with the addition of an aldosterone receptor antagonist (ARA) such as spironolactone or eplerenone. Reductions in mortality and hospitalizations have
been observed with the addition of an ARA to ACE inhibitor and β­blocker therapy in patients with symptomatic HF (NYHA classes II­IV). Strict serum
potassium and creatinine monitoring is necessary and therapy should be avoided if serum potassium is more than 5 mEq/L or creatinine clearance is
less than 30 mL/min. The risk of hyperkalemia is increased in patients on concomitant ACE inhibitors, ARBs, NSAIDs, and cyclooxygenase­2 (COX­2)
inhibitors. Eplerenone is more selective for aldosterone receptors, resulting in less gynecomastia than spironolactone.

Hydralazine and Isosorbide Dinitrate

Several proposed mechanisms support the combined use of hydralazine and isosorbide dinitrate (ISDN) for HF. Hydralazine is an arterial vasodilator
and ISDN is a venous vasodilator and also increases nitric oxide. Hydralazine also possesses antioxidant properties which eliminates the need for a
nitrate­free interval with ISDN; hence, dosing around the clock or every 8 hours is warranted. Combination therapy is associated with a reduction in
mortality among African Americans who remain symptomatic despite background therapy with an ACE inhibitor and β­blocker. Importantly, ACE
inhibitor/ARB should be continued when initiating ISDN and hydralazine therapy in African American patients. In contrast, the combination may be
substituted in patients of any race who cannot tolerate an ACE inhibitor or ARB. Dizziness and headache are the most common adverse effects with
hydralazine and ISDN therapy, although intiation of low doses or temporary reduction of the dose may improve tolerability.
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Ivabradine
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Elevated HR has been associated with poor outcomes in HF, and some patients may be unable to tolerate target doses of β­blocker therapy. Ivabradine
and ISDN is a venous vasodilator and also increases nitric oxide. Hydralazine also possesses antioxidant properties which eliminates the need for a
Khona reduction
nitrate­free interval with ISDN; hence, dosing around the clock or every 8 hours is warranted. Combination therapy is associated with Kaen University
in
mortality among African Americans who remain symptomatic despite background therapy with an ACE inhibitor and β­blocker. Importantly,
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inhibitor/ARB should be continued when initiating ISDN and hydralazine therapy in African American patients. In contrast, the combination may be
substituted in patients of any race who cannot tolerate an ACE inhibitor or ARB. Dizziness and headache are the most common adverse effects with
hydralazine and ISDN therapy, although intiation of low doses or temporary reduction of the dose may improve tolerability.

Ivabradine

Elevated HR has been associated with poor outcomes in HF, and some patients may be unable to tolerate target doses of β­blocker therapy. Ivabradine
is an inhibitor of If current in the sinoatrial node, leading to reductions in HR without affecting contractility. A reduction in hospitalizations for HF was
observed with ivabradine in patients with resting HR 70 beats per minute (bpm) or more in normal sinus rhythm who remained symptomatic despite
maximally tolerated β­blocker therapy. Therapy should be adjusted to a maximum of 7.5 mg twice daily to maintain HR between 50 and 60 bpm.
Bradycardia and visual disturbances are the most common adverse effects of ivabradine. Of note, ivabradine is a CYP3A4 substrate and its use is
contraindicated with strong CYP3A4 inhibitors.

Digoxin

Digoxin may have neurohormone­modulating effects that confer benefit in patients with advanced HF. Digoxin improves symptoms and reduces
hospitalizations but does not impact mortality. Its use should be reserved for advanced disease (ie, symptomatic HF despite standard therapy). Low
doses (eg, 125­250 mcg/d) are recommended and serum digoxin concentrations should be maintained in the range of 0.5 to 0.9 ng/mL. Due to an
extended distribution phase, serum digoxin concentrations should be obtained no earlier than 6 hours, but preferably 12 to 24 hours following
administration. Dose reductions may be required in older patients, impaired renal function, or low body weight. Common adverse effects include
bradycardia, altered mental status, gastrointestinal upset, and visual disturbances (see Table 1­2).

Nonpharmacologic Therapy

There are several important lifestyle changes that all patients with HF should adopt. Patients should be counseled to eat a heart­healthy diet low in
sodium (<3 grams daily) and to weigh themselves each morning on the same scale while wearing the same amount of clothing. Patients should contact
their health care provider if they gain more than 1 pound in 1 day or 5 pounds in 1 week. Patients should also be counseled to exercise regularly and
avoid alcohol, cigarettes, and illicit substances.

Ventricular arrhythmias and sudden cardiac death are major causes of mortality in HF patients. In addition to lifestyle management, placement of an
implantable cardioverter defibrillator (ICD) is recommended to reduce mortality in patients with an EF of 35% or less despite standard HF therapy.
Ventricular dyssynchrony may compromise CO and use of a biventricular pacemaker with cardiac resynchronization therapy (CRT) is associated with a
reduction in hospitalizations and improved QOL. Patients with symptomatic HF and EF of 35% or less and a QRS interval of 150 ms or more are eligible
for CRT. An ICD and/or CRT may be considered in select patients with less severe HF and other electrocardiographic findings, but a discussion of these
indications is beyond the scope of this review.

Heart Failure with Preserved Ejection Fraction

Drug therapies associated with clinical improvement in patients with HFrEF have mostly failed to produce similar outcomes in patients with HFpEF. Use
of ARBs and aldosterone antagonists has been associated with improvements in hospitalizations whereas other therapies have had no impact on
clinical endpoints or have produced conflicting results. As a result, recommendations for the treatment of HFpEF focus on symptomatic relief and
management of common comorbidities, such as HTN and coronary artery disease. Diuretics should be considered for those with HFpEF and volume
overload while comorbidities should be managed according to established practice guidelines for each specific condition.

TAKEAWAY POINTS

TAKEAWAY POINTS

Common causes of HF are coronary artery disease and uncontrolled HTN.

HF may result from impaired ventricular ejection (HFrEF), impaired filling/HF with preserved EF (HFpEF), or both.

HF is categorized by two classification systems. The ACC/AHA staging system classifies patients according to the progression of HF as being at
risk for HF (stage A), having structural heart disease without symptoms (stage B), having HF signs and symptoms (stage C), or end­stage HF
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system categorizes patients as being asymptomatic (class I), symptomatic with mild or moderate
Chapter 1: Chronic Heart Failure, Jo E. Rodgers;orBrent
physical activity (class II or III, respectively), N. Reedat rest (class IV).
symptomatic
Page 8 / 11
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Patients with HF often present with signs and symptoms of volume overload such as dyspnea on exertion and lower extremity edema. Signs and
symptoms of low CO (eg, fatigue) are less common.
management of common comorbidities, such as HTN and coronary artery disease. Diuretics should be considered for those with HFpEF and volume
overload while comorbidities should be managed according to established practice guidelines for each specific condition. Khon Kaen University
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TAKEAWAY POINTS

TAKEAWAY POINTS

Common causes of HF are coronary artery disease and uncontrolled HTN.

HF may result from impaired ventricular ejection (HFrEF), impaired filling/HF with preserved EF (HFpEF), or both.

HF is categorized by two classification systems. The ACC/AHA staging system classifies patients according to the progression of HF as being at
risk for HF (stage A), having structural heart disease without symptoms (stage B), having HF signs and symptoms (stage C), or end­stage HF
(stage D). The NYHA functional classification system categorizes patients as being asymptomatic (class I), symptomatic with mild or moderate
physical activity (class II or III, respectively), or symptomatic at rest (class IV).

Patients with HF often present with signs and symptoms of volume overload such as dyspnea on exertion and lower extremity edema. Signs and
symptoms of low CO (eg, fatigue) are less common.

Activation of neurohormonal pathways such as the SNS and RAAS occur in HF, resulting in vasoconstriction, sodium and fluid retention, and
cardiac remodeling. Treatment strategies in HFrEF target these systems.

The goals of HF drug therapy include a reduction in mortality, prevention of disease progression, reduction in hospitalizations, and
improvement in QOL.

Lifestyle modifications such as fluid and sodium restriction are important for maintaining fluid balance, although loop diuretic therapy is often
required. Addition of a thiazide diuretic may be considered in diuretic­refractory patients.

Both ACE inhibitors and β­blockers reduce mortality in HF patients and are considered cornerstones of therapy.

An ARB should be considered in patients with intolerable cough or angioedema with an ACE inhibitor.

Substitution of sacubitril/valsartan for ACE inhibitor or ARB therapy should be considered in patients who remain symptomatic despite
receiving an ACE inhibitor or ARB and a β­blocker.

Addition of an ARA to an ACE inhibitor and β­blocker reduces mortality and hospitalizations in symptomatic HF patients. Close monitoring of
serum potassium and renal function is imperative, and ARA therapy should be avoided in the setting of hyperkalemia or renal dysfunction.

The combination of ISDN and hydralazine reduces mortality in African Americans who remain symptomatic despite standard HF therapy.
Therapy should also be considered for patients of any race who are intolerant to ACE inhibitors and ARBs.

Ivabradine may be considered for reducing the risk of hospitalization in patients with resting HR o f 70 bpm or more in normal sinus rhythm
who remain symptomatic despite maximally tolerated doses of β­blocker therapy.

Digoxin reduces hospitalizations and improves HF symptoms. It may be considered for patients symptomatic despite standard HF therapy.
Digoxin concentrations should be maintained at less than 1 ng/mL.

Implantation of an ICD significantly reduces sudden cardiac death and should be considered in eligible patients. Biventricular pacing with CRT
provides symptomatic improvement and reduces hospitalizations, but has not been shown to reduce mortality.

Few therapies have been shown to improve clinical outcomes in patients with HFpEF. Recommendations for treatment focus on symptomatic
relief and adequate control of common comorbidities, such as HTN and coronary artery disease.

BIBLIOGRAPHY

Katzung BG. Drugs used in heart failure. In: Katzung BG, Masters SB, Trevor AJ. eds. Basic & Clinical Pharmacology. 12th ed. New York, NY: McGraw­
Hill; 2012:chap 13.

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Mann DL, Chakinala 2:36 A
M. Heart Yourand
failure IP is 202.28.119.100
cor pulmonale. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's
Chapter
Principles of Internal Medicine . 18th ed. New York, Brent
1: Chronic Heart Failure, Jo E. Rodgers; N. Reed 2012;chap 234.
NY: McGraw­Hill;
Page 9 / 11
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Maron BA, Rocco TP. Pharmacotherapy of congestive heart failure. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's The
BIBLIOGRAPHY
Khon Kaen University
Access Provided by:
Katzung BG. Drugs used in heart failure. In: Katzung BG, Masters SB, Trevor AJ. eds. Basic & Clinical Pharmacology. 12th ed. New York, NY: McGraw­
Hill; 2012:chap 13.

Mann DL, Chakinala M. Heart failure and cor pulmonale. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's
Principles of Internal Medicine . 18th ed. New York, NY: McGraw­Hill; 2012;chap 234.

Maron BA, Rocco TP. Pharmacotherapy of congestive heart failure. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's The
Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw­Hill; 2011;chap 28.

Parker RB, Nappi JM, Cavallari LH. Chapter 14. Chronic Heart Failure. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. eds.
Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw­Hill; 2016.

Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A
Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of
America. Circulation. 2017;136(6):e137–e161. [PubMed: 28455343]

Yancy CW, Jessup M, Wilkoff BL, et al; for the American College of Cardiology Foundation; American Heart Association Task Force on Practice
Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart
Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147–239. [PubMed: 23747642]

KEY ABBREVIATIONS
ACE­I = angiotensin­converting enzyme­inhibitor

ACCF = American College of Cardiology Foundation

AHA = American Heart Association

ARA = aldosterone receptor antagonist

ARB = angiotensin receptor blocker

BNP = B­type natriuretic peptide

BP = blood pressure

CO = cardiac output

COPD = chronic obstructive pulmonary disease

COX­2 = cyclooxygenase­2

CRT = cardiac resynchronization therapy

EF = ejection fraction

HF = heart failure

HFpEF = heart failure with preserved ejection fraction

HFrEF = heart failure with reduced ejection fraction

HR = heart rate

HTN = hypertension

ICD = implantable cardioverter defibrillator

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ISDN = isosorbide dinitrate
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JVD = jugular vein distention

MI = myocardial infarction
 HR = heart rate Khon Kaen University
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HTN = hypertension

ICD = implantable cardioverter defibrillator

ISDN = isosorbide dinitrate

JVD = jugular vein distention

MI = myocardial infarction

NIOSH = National Institute for Occupational Safety and Health

NSAIDs = nonsteroidal anti­inflammatory drugs

NYHA = New York Heart Association

PND = paroxysmal nocturnal dyspnea

QOL = quality of life

RAAS = renin angiotensin aldosterone system

RR = respiration rate

SNS = sympathetic nervous system

SOB = shortness of breath

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