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STEMI, Acute Coronary
Syndrome, CHF
Which one of the following statements about acute
management of ST-segment elevation myocardial
infarction (STEMI) is correct?
A. From the time of contact with the patient, the goal
is for reperfusion to begin within 12 hours.
B. Once symptoms of STEMI are recognized,
patients should immediately chew aspirin (162 to
325 mg), unless there is an absolute contraindication.
C. Patients should take one dose of nitroglycerin
sublingually at the onset of symptoms and seek
medical attention if they do not improve within 30
minutes.
D. Intravenous beta blocker therapy is the standard
of care in patients with STEMI; these agents should
be administered daily to hemodynamically stable
patients starting within 24 hours.
Answer
• B. Once symptoms of STEMI are
recognized, patients should immediately
chew aspirin (162 to 325 mg), unless there
is an absolute contraindication.
Which one of the following
conditions is a contraindication
for intravenous beta blocker
therapy in patients with STEMI?
A. First-degree heart block.
B. Systolic blood pressure greater
than 140 mm Hg.
C. Age 70 years or younger.
D. Evidence of low cardiac
output state.
Answer
• D. Evidence of low cardiac output state.
A 52-year-old man with a body mass index of 31 kg
per m2 who has hypertension and diabetes underwent
percutaneous coronary intervention without stent
placement after STEMI. Which of the following
management strategies is/are appropriate?
A. Drug therapy should be initiated to lower lowdensity lipoprotein cholesterol levels to less than 100
mg per dL (2.60 mmol per L).
B. Angiotensin-converting enzyme inhibitor therapy
should be initiated.
C. Treatment with aspirin should continue
indefinitely in combination with clopidogrel (Plavix)
for at least 14 days after the event.
D. The initial goal of weight loss should be to reduce
body weight by approximately 5 percent from
Answer
• A. Drug therapy should be initiated to lower
low-density lipoprotein cholesterol levels to
less than 100 mg per dL (2.60 mmol per L).
B. Angiotensin-converting enzyme inhibitor
therapy should be initiated.
C. Treatment with aspirin should continue
indefinitely in combination with clopidogrel
(Plavix) for at least 14 days after the event.
Which of the following statements about the
treatment guidelines for STEMI is/are correct?
A. Patients who previously took nonsteroidal antiinflammatory drugs should continue taking these
agents after STEMI.
B. The most important point in STEMI management
is minimizing the time from symptom onset to
initiation of reperfusion therapy with fibrinolysis or
percutaneous coronary intervention.
C. Oral beta blocker therapy should be initiated
within the first 24 hours, in the absence of
contraindications.
D. The addition of 75 mg of clopidogrel to daily
aspirin therapy should be considered even if the
patient did not undergo reperfusion.
Answer
• B. The most important point in STEMI
management is minimizing the time from
symptom onset to initiation of reperfusion therapy
with fibrinolysis or percutaneous coronary
intervention.
C. Oral beta blocker therapy should be initiated
within the first 24 hours, in the absence of
contraindications.
D. The addition of 75 mg of clopidogrel to daily
aspirin therapy should be considered even if the
patient did not undergo reperfusion.
ST-segment elevation
myocardial infarction
•
The American College of Cardiology and American Heart Association, in
collaboration with the Canadian Cardiovascular Society, have issued an
update of the 2004 guideline for the management of patients with STsegment elevation myocardial infarction.
• The American Academy of Family Physicians endorses and accepts this
guideline as its policy.
• Early recognition and prompt initiation of reperfusion therapy remains the
cornerstone of management of ST-segment elevation myocardial
infarction.
• Aspirin should be given to symptomatic patients.
• Beta blockers should be used cautiously in the acute setting because they
may increase the risk of cardiogenic shock and death.
• The combination of clopidogrel and aspirin is indicated in patients who
have had ST-segment elevation myocardial infarction.
• A stepped care approach to analgesia for musculoskeletal pain in patients
with coronary heart disease is provided.
• Cyclooxygenase inhibitors and nonsteroidal anti-inflammatory drugs
increase mortality risk and should be avoided.
• Primary prevention is important to reduce the burden of heart disease.
Secondary prevention interventions are critically important to prevent
recurrent events in patients who survive.
STEMI
•
•
•
•
•
Patients with STEMI who present within 12 hours of symptom onset and who do not have
contraindications should receive immediate reperfusion therapy with fibrinolysis or PCI.
•
Class I, LOE A
•
A
•
Patients with STEMI should immediately chew 162 to 325 mg of aspirin on recognition of
symptoms, unless there is an absolute contraindication.
•
Class I, LOE A
•
A
Intravenous beta blockers should not be given to patients with STEMI. They may be considered for
treatment of hypertension if there are no contraindications (see Table 1).
•
Class III, LOE A
•
A
Oral clopidogrel (Plavix) at a dosage of 75 mg daily should be added to aspirin therapy in patients
with STEMI, whether or not they undergo reperfusion therapy.
•
Class I, LOE A
•
A
•
Oral beta blocker therapy should be initiated within 24 hours of STEMI in patients with no
contraindications.
•
Class I, LOE B
•
B
Patients undergoing reperfusion with PCI or stenting should begin clopidogrel therapy. Duration of
therapy varies, depending on the type of stent used (no stent, 14 days; bare-metal stent, at least
one month but ideally one year unless patient is at increased risk of bleeding; drug-eluting stent,
one year).
•
Class I, LOE B
•
B
Patients who routinely took nonsteroidal anti-inflammatory drugs (except for aspirin) before STEMI
should discontinue these agents because of increased risks of mortality, reinfarction, hypertension,
heart failure, and myocardial rupture.
STEMI
•
•
•
•
•
•
If patients with STEMI have cardiogenic shock, they should be transported to a facility capable of
cardiac catheterization and rapid revascularization (PCI and coronary artery bypass graft surgery).
Patients with contraindications to fibrinolysis should be immediately transported to such a facility,
or transferred within 30 minutes.
•
It is also reasonable to consider an invasive strategy in patients with severe congestive heart
failure (CHF).
•
The strategy for facilitated PCI that was proposed in the 2004 guideline, in which higher-risk
patients with low bleeding risk receive full-dose fibrinolysis and subsequent PCI, may be harmful
and is no longer recommended.
More study is required before clear recommendations can be made on other facilitated strategies
(i.e., half-dose fibrinolysis, a glycoprotein IIb/IIIa inhibitor, or both).
These strategies may be considered when patients are at high risk and PCI is not available within
90 minutes, provided bleeding risk is low (i.e., in younger patients and those with normal body
weight, and in the absence of poorly controlled hypertension).
Rescue PCI after failed thrombolysis is still appropriate and should be performed in patients who
fail fibrinolysis, as evidenced by shock, severe CHF or pulmonary edema (Killip class III or greater),
or hemodynamically compromising ventricular arrhythmias.
•
Rescue PCI is reasonable in patients who have less than 50 percent resolution of ST-segment
elevation 90 minutes after initiation of fibrinolytic therapy and a moderately large area of
myocardium at risk.
•
The routine use of intravenous beta blocker therapy in the acute phase of STEMI is not
recommended because of the increased risk of cardiogenic shock, based on findings from the
COMMIT/CCS-2 study (Clopidogrel and Metoprolol in Myocardial Infarction Trial/Second Chinese
Cardiac Study).4
However, it is reasonable to use intravenous beta blocker therapy in the acute setting to manage
hypertension in patients with STEMI who have none of the contraindications listed in Table 1.5
•
Daily oral beta blocker therapy should be initiated within 24 hours to hemodynamically stable
patients who have no contraindications; these agents are also important in secondary prevention.
Changes in Post-STEMI
Management
•
Patients who receive pharmacologic reperfusion therapy should receive subsequent
anticoagulation therapy for a minimum of 48 hours.
•
There is no evidence of benefit for unfractionated heparin beyond 48 hours unless
there are ongoing indications for anticoagulation.
•
Low-molecular-weight heparin may be used instead for the duration of the
hospitalization, up to eight days, if the patient has no significant renal dysfunction.
•
The update lists effective anticoagulation regimens.1
•
The 2004 guideline contained no specific recommendation for dual antiplatelet
therapy with clopidogrel (Plavix) plus low-dose aspirin in patients at high risk of
atherothrombotic events.
•
The update recommends that 75 mg of oral clopidogrel be added to daily aspirin,
whether or not the patient underwent reperfusion; this change is summarized in Table
2.1
•
Treatment with clopidogrel should continue for at least 14 days.
•
Long-term maintenance therapy (e.g., one year) may be useful in these patients.
•
It is reasonable to start clopidogrel therapy with a 300-mg oral loading dose in
patients younger than 75 years; no data are available for older patients.
•
In patients with bare-metal stents, clopidogrel should be continued for at least one
month; it should be continued for several months in patients with drug-eluting stents
(at least three months for sirolimus [Rapamune], six months for paclitaxel [Taxol])
and 12 months in patients who are not at high risk of bleeding.
•
The guideline update does not address whether longer-term clopidogrel therapy is
needed in patients with drug-eluting stents.
Secondary Prevention for
Patients with STEMI
•
Intervention
Recommendation and ACC/AHA level of evidence*
•
Smoking cessation
•
Ask about tobacco use at every visit I(B)
•
Advise every patient who uses tobacco to quit I(B)
•
Assess the patient's willingness to quit I(B)
•
Assist by counseling and developing a plan for quitting I(B)
•
Arrange follow-up, referral to special programs, or pharmacotherapy (including nicotine replacement therapy) I(B)
•
Urge avoidance of exposure to environmental tobacco smoke at work and at home I(B)
Blood pressure control (less than 140/90 mm Hg, or less than 130/80 mm Hg in patients with diabetes or chronic kidney disease)
Initiate or maintain lifestyle modification in all patients (weight control; increased physical activity; alcohol moderation; sodium
reduction; increased consumption of fresh fruits, vegetables, and low-fat dairy products) I(B)
If blood pressure is 140/90 mm Hg or greater (or 130/80 mm Hg or greater in patients with diabetes or chronic kidney disease), start
beta blockers and/or ACE inhibitors, then add thiazides or other agents as needed I(A)
Lipid management (LDL-C level substantially less than 100 mg per dL [2.60 mmol per L]; non-HDL-C level† less than 130 mg per dL
[3.35 mmol per L] in patients with triglyceride levels 200 mg
per dL [2.26 mmol per L] or greater)
Start dietary therapy in all patients. Reduce intake of trans-fatty acids, saturated fat (to less than 7 percent of total calories), and
cholesterol (to less than 200 mg per day) I(B)
•
Reasonable to add plant stanols or sterols (2 g per day) and viscous fiber (more than 10 g per day) to lower
LDL-C level IIa(A)
•
Promote daily physical activity and weight management I(B)
•
Reasonable to encourage increased consumption of omega-3 fatty acids in the form of fish‡ or in capsule form
(1 g per day) for risk reduction. For treatment of elevated triglyceride levels, higher dosages are usually necessary for risk reduction
IIb(B)
Assess fasting lipid levels in all patients, and within 24 hours of hospitalization for STEMI. For hospitalized patients, initiate lipidlowering therapy before discharge according to the following schedule: I(A)
•
• LDL-C level should be substantially less than 100 mg per dL I(A)
•
• Further reduction of LDL-C level to less than 70 mg per dL (1.80 mmol per L) is reasonable IIa(A)
•
• If baseline LDL-C level is 100 mg per dL or greater, initiate LDL-lowering drug therapy§ I(A)
• If therapy lowers LDL-C level to 100 mg per dL or greater, intensify therapy (may require LDL-C-lowering drug combination)|| I(A)
•
• If baseline LDL-C level is 70 to 100 mg per dL, it is reasonable to treat to less than 70 mg per dL IIa(B)
• If triglyceride level is 150 mg per dL (1.70 mmol per L) or greater, or if HDL-C level is less than 40 mg per dL (1.05 mmol per L),
weight management, physical activity, and smoking cessation should be emphasized I(B)
• If triglyceride level is 200 to 499 mg per dL (2.26 to 5.64 mmol per L), non-HDL-C level should be less than 130 mg per dL IIa(B)
•
• Further reduction of non-HDL-C level to less than 100 mg per dL is reasonable IIa(B)
Therapeutic options to reduce non-HDL-C level include more intense LDL-C-lowering therapy I(B), niacin therapy¶ (after LDL-Clowering therapy) IIa(B), or fibrate therapy¶ (after LDL-C-lowering therapy) IIa(B)
If triglyceride level is 500 mg per dL (5.66 mmol per L),** therapeutic options to prevent pancreatitis include fibrate¶ or niacin¶ before
LDL-C-lowering therapy; treat LDL-C to goal after triglyceride-lowering therapy. Achieve non-HDL-C level of less than 130 mg per dL
•
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•
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•
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•
•
Secondary Prevention for Patients with STEMI
•
Physical activity
(30 minutes at least five days per week)
•
Assess risk with a physical activity history or an exercise test to guide prescription I(B)
•
Encourage 30 to 60 minutes of moderate-intensity aerobic activity on most (and preferably all) days of the week, supplemented by an increase in
daily lifestyle activities (e.g., walking breaks at work, gardening, household work) I(B)
•
Reasonable to encourage resistance training two days per week IIb(C)
•
Advise medically supervised programs for high-risk patients (e.g., those with recent acute coronary syndromes or revascularization) I(B)
•
Weight management (BMI 18.5 to 24.9 kg per m2; waist circumference less than 40 inches in men, less than 35 inches in women)
•
Assess BMI and waist circumference at each visit and encourage weight maintenance or reduction through an appropriate balance of physical
activity, caloric intake, and behavioral programs when indicated I(B)
•
If waist circumference (measured horizontally at the iliac crest) is 35 inches or more in women and 40 inches or more in men, initiate lifestyle
changes and consider treatment strategies for metabolic syndrome as indicated I(B)
•
The initial goal of weight loss therapy should be to reduce body weight by approximately 10 percent from baseline. Further weight loss can be
attempted if indicated I(B)
•
Diabetes manage-ment (A1C less than 7 percent)
•
Initiate lifestyle modification and pharmacotherapy to achieve near-normal A1C level I(B)
•
Begin vigorous modification of other risk factors (e.g., physical activity, weight management, blood pressure control, lipid management) I(B)
•
Antiplatelet and anticoagulant therapy
•
Aspirin
•
Start aspirin at a dosage of 75 to 162 mg daily and continue indefinitely in all patients unless contraindicated I(A)
•
Increase dosage to 162 to 325 mg daily in patients with bare metal stent (one-month course) and in those with drug-eluting stents (three-month
course for sirolimus [Rapamune]; six-month course for paclitaxel [Taxol]). After high-dose course, continue indefinitely at a dosage of 75 to 162 mg
per day I(B)
•
If bleeding is a concern, a lower dosage after stenting is reasonable IIa(C)
•
Clopidogrel (Plavix)
•
Start and continue clopidogrel at a dosage of 75 mg daily after PCI with stent placement (minimum of one month and up to 12 months for bare-metal
stent [two weeks if patient is at increased risk of bleeding], at least 12 months for drug-eluting stent if patient is not at increased risk of bleeding) I(B)
•
Long-term daily maintenance therapy (one year) with 75 mg of clopidogrel is reasonable in patients with STEMI, regardless of whether they
underwent reperfusion with fibrinolytic therapy IIa(C)
•
Continue clopidogrel for at least 14 days after PCI without stent placement I(B)
•
Warfarin (Coumadin)
•
Manage warfarin therapy to achieve an INR of 2.0 to 3.0 in patients after STEMI when clinically indicated
(e.g., atrial fibrillation, left ventricular thrombus) I(A)
•
Monitor patients closely, because the use of warfarin in conjunction with aspirin or clopidogrel is associated with an increased risk of bleeding I(B)
•
In patients who require warfarin, clopidogrel, and aspirin therapy, an INR of 2.0 to 2.5 is recommended, with low-dose aspirin (75 to 81 mg) and
clopidogrel (75 mg) I(C)
•
Renin-angiotensin-aldosterone system blocker therapy
•
ACE inhibitors
•
Start ACE inhibitors in patients with an LVEF of 40 percent or less, and in those with hypertension, diabetes,
or chronic renal disease, unless contraindicated I(A)
•
Consider ACE inhibitor therapy in all other patients I(B)
•
Angiotensin receptor blockers
•
Start angiotensin receptor blockers in patients who are intolerant of ACE inhibitors and in those with clinical
or radiologic signs of HF or an LVEF of 40 percent or less I(A)
•
Aldosterone blockers
•
Start aldosterone blockers in patients without significant renal dysfunction†† or hyperkalemia‡‡ who are already receiving therapeutic doses of an
ACE inhibitor and beta blocker, and who have an LVEF of 40 percent or less and have diabetes or HF I(A)
•
Beta blocker therapy
•
Start and continue indefinitely in all patients unless contraindicated I(A)
•
Influenza vaccination
Recommendations
•
‡-Pregnant and lactating women should limit their intake of fish to minimize exposure
to methylmercury.
•
§-When LDL-lowering medications are used, a 30 to 40 percent reduction in LDL-C
levels should be obtained. If an LDL-C level of less than 70 mg per dL is desired,
consider drug titration to minimize side effects and cost. When an LDL-C level of less
than 70 mg per dL is not achievable because of high baseline LDL-C levels, it may be
possible to achieve LDL-C reductions of greater than 50 percent by using statins or
LDL-C-lowering drug combinations.
•
||-Standard dose of statin with ezetimibe (Zetia), bile acid sequestrant, or niacin.
(note: This guideline update was published before the controversy over ezetimibe.)
•
¶-The combination of high-dose statin plus fibrate can increase the risk of severe
myopathy. Statin doses should be kept relatively low with this combination.
Supplemental dietary niacin must not be used as a substitute for prescription niacin,
and over-the-counter niacin should be used only if approved and monitored by a
physician.
•
**-Patients with very high triglyceride levels should not consume alcohol. The use of
bile acid sequestrants is relatively contraindicated when triglyceride levels are
greater than 200 mg per dL.
•
††-Creatinine levels should be less than 2.5 mg per dL (220 µmol per L) in men and
less than 2.0 mg per dL (180 µmol per L) in women.
•
‡‡-Potassium levels should be less than 5.0 mEq per L (5.0 mmol per L).
•
Adapted from Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the
management of patients with ST-elevation myocardial infarction: a report of the
American College of Cardiology/American Heart Association Task Force on Practice
Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients
with Acute Myocardial Infarction) [published corrections appear in Circulation.
2005;111(15):2013-2014, and Circulation. 2007;115(15):e411]. Circulation.
2004;110(9):e213-e214.
acute coronary syndrome
• The diagnosis of acute coronary ischemia
depends upon the characteristics of the
chest pain, and specific associated
symptoms, abnormalities on
electrocardiogram (ECG), and levels of
serum markers of cardiac injury. A patient
with a possible acute coronary syndrome
(ACS) should be treated rapidly. Thus,
initial management steps must be
undertaken before or during the time the
diagnosis is being established.
IMMEDIATE ED MANAGEMENT
• — In the emergency department (ED), patients presenting
with chest pain should be rapidly evaluated to determine if
the symptoms are suggestive of acute ischemia, or Caution
should be employed in evaluating possible acute coronary
syndrome (ACS) in women, diabetics, and the elderly, who
are more likely to present with "atypical" symptoms even
in the presence of acute coronary ischmic pain protocol
should be implemented if the history or symptoms are
suggestive of acute ischemia. The time for initial
assessment, including ECG, and preliminary management
of a patient with possible acute coronary ischemia is
ideally 10 minutes from presentation (show algorithm 1)
[6]. Data from a national registry have shown that ECG
acquisition is frequently delayed, and that women are
significantly less likely to have ECGs performed within the
recommended 10-minute period
• During the initial assessment phase, the
following steps should be accomplished for any
patient with significant risk of ACS:
• Airway, breathing, and circulation assessed
• 12-lead ECG obtained
• Resuscitation equipment brought nearby
• Cardiac monitor attached
• Oxygen given
• IV access and blood work obtained
• Aspirin 162 to 325 mg given
• Nitrates and morphine given (unless
contraindicated)
• Twelve-lead ECG - A 12-lead ECG should be
obtained in all patients with possible coronary
ischemia. (See "ECG-based management" below).
The 12-lead ECG provides the basis for initial
diagnosis and management and should
immediately be shown to an experienced
emergency clinician for interpretation.
• The initial ECG is often NOT diagnostic in
patients with ACS. The ECG should be repeated at
5 to 10 minute intervals if the initial ECG is not
diagnostic but the patient remains symptomatic
and there is a high clinical suspicion for MI [6].
(See "ECG-based management" below, section on
Serial ECGs).
• Pain that responds to sublingual nitroglycerin is
frequently thought to have a cardiac etiology or to
be due to esophageal spasm. However, pain relief
with nitroglycerin in an acute care setting is not
helpful in distinguishing cardiac from noncardiac
chest pain [9]. In a study of 459 patients who
presented to an emergency department with chest
pain and were admitted to the hospital, the
percentage of patients who had relief of chest pain
with nitroglycerin was similar among the 141
patients with active CHD and the 275 patients
without active CHD (35 versus 41 percent
experienced relief)
• Morphine - Intravenous morphine sulfate at
an initial dose of 2 to 4 mg, with increments
of 2 to 8 mg, repeated at 5 to 15 minute
intervals, should be given for the relief of
chest pain and anxiety [6]. Morphine can
reduce sympathetic stimulation caused by
pain and anxiety, thereby decreasing cardiac
workload and risks associated with excess
catecholamines.
• LBBB or pacing - Both LBBB, which is present in
approximately 7 percent of patients with an acute
MI, and pacing can interfere with the
electrocardiographic diagnosis of coronary
ischemia. Another problem is that approximately
one-half of patients with LBBB and an acute MI
do not have chest pain as a symptom of their
ischemia [17]. As a result, patients with LBBB are
much less likely to receive aspirin, beta blockers,
and reperfusion therapy [18], particularly if they
present without chest pain [17]. Similar
observations have been made in patients with a
paced rhythm [19].
• However, primary PCI is not available at all institutions,
there are often delays in implementation, and local
expertise is an important determinant of outcome. As a
result, the ACC/AHA task force gave a class I
recommendation to the use of thrombolytic therapy for any
patient with an acute STEMI without contraindications for
thrombolysis (show table 2), who presents to a facility
without the capability for expert, prompt intervention with
primary PCI within 90 minutes of first medical contact [6].
Thrombolytic therapy was also recommended if the
relative delay necessary to perform primary PCI (the
expected door-to-balloon time minus the expected door-toneedle time) is greater than one hour. The delay from
patient arrival to administration of thrombolytics should be
less than 30 minutes [6]
• Aspirin - Aspirin is the preferred antiplatelet agent
and should be given in a dose of 162 to 325 mg to
chew and swallow as soon as possible to any
patient with STEMI.
•
- Clopidogrel - The 2004 ACC/AHA and
ACCP guidelines both gave a class I
recommendation to the use of clopidogrel in all
patients treated with primary PCI and stenting
[6,21]. We recommend a 600 mg loading dose in
these patients because studies have shown that six
hours is needed to demonstrate a reduction in
thrombotic complications if 300 mg is used, and
primary PCI should be done within 90 minutes.
Limited trial data suggest that 600 mg works
within two to three hours and that outcomes may
•
•
•
•
•
Beta blockers - The 2004 ACC/AHA task force on the management of ST
elevation MI recommended that beta blocker therapy be administered
universally to all patients without contraindications, irrespective of
concomitant fibrinolytic therapy or performance of primary PCI [6]. The major
complication of beta blocker therapy in the setting of ST elevation MI is
cardiogenic shock. Care should be taken to assure that cardiac output is
adequate for beta blocker therapy.
Although no specific dosing regimen was written in the guidelines, most
experts recommend early intravenous beta blockade using a cardioselective
agent such as metoprolol or atenolol:
- Intravenous metoprolol can be given in 5 mg increments by slow
intravenous administration (5 mg over one to two minutes), repeated every
five minutes for a total initial dose of 15 mg. Patients who tolerate this
regimen should then receive oral therapy beginning 15 minutes after the last
intravenous dose (25 to 50 mg every six hours for 48 hours) followed by a
maintenance dose of 100 mg twice daily.
- Intravenous atenolol can be given in a 5 mg dose followed by another 5
mg five minutes later. Patients who tolerate this regimen should then receive
oral therapy beginning one to two hours after the last intravenous dose (50 to
100 mg/day).
- Esmolol (50 mcg/kg per min increasing to a maximum of 200 to 300
mcg/kg per min) can be used if an ultrashort acting beta blocker is required.
(See "Beta blockers in the management of acute coronary syndrome").
CHF Systolic Dysfunction
•
Class I - There is evidence and/or general agreement that the following approaches are effective
in the management of patients with current or prior symptoms of HF and a reduced
LVEF Diuretics and salt restriction for fluid retention. Angiotensin converting enzyme (ACE)
inhibitors in all patients, unless contraindicated. Beta blockers in all stable patients, unless
contraindicated. One of the three beta blockers proven to reduce mortality should be used (bisoprolol,
carvedilol, and sustained release metoprolol succinate. Angiotensin II receptor blockers (ARBs) in
patients who do not tolerate ACE inhibitors. Drugs that can adversely affect the patient's clinical
status should be avoided or withdrawn, if possible. These include nonsteroidal antiinflammatory
drugs, most antiarrhythmic drugs, and most calcium channel blockers. Exercise training as an
adjunctive approach to improve clinical status in ambulatory patients. An implantable cardioverterdefibrillator (ICD) for secondary prevention to prolong survival in patients with a history of cardiac
arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia. An ICD for
primary prevention to reduce total mortality by preventing sudden cardiac death (SCD) in patients
with non-ischemic or ischemic heart disease who meet the following criteria: at least 40 days postmyocardial infarction, an LVEF 35 percent, New York Heart Association functional class II or III
symptoms despite optimal chronic medical therapy, and a reasonable expectation of survival with a
good functional status for more than one year. Cardiac resynchronization therapy (CRT), with or
without an ICD, unless contraindicated, in patients who meet the following criteria: cardiac
dyssynchrony as defined by a QRS duration >120 msec, LVEF 35 percent, sinus rhythm, and New
York Heart Association functional class III or ambulatory class IV symptoms despite optimal
medical therapy. Addition of an aldosterone antagonist is recommended in selected patients with
moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for
preserved renal function and normal potassium concentration. Creatinine should be 2.5 mg per dl in
men or 2.0 mg per dl in women and potassium should be <5.0 mEq per liter. Under circumstances in
which monitoring for hyperkalemia and renal dysfunction is not anticipated to be feasible, the risks
may outweigh the benefits of aldosterone antagonists. The combination of hydralazine and nitrates is
recommended to improve outcomes for patients self-described as African-Americans, with moderatesevere symptoms on optimal therapy with ACE inhibitors, beta blockers, and diuretics..
CHF Systolic Dysfunction
•
Class IIa - The weight of evidence and/or opinion is in favor of the
following approaches being effective in the management of patients with
current or prior symptoms of HF and a reduced LVEF It is reasonable to
treat patients with atrial fibrillation and HF with a strategy to maintain sinus
rhythm or with a strategy to control ventricular rate alone. Maximal exercise
testing with or without measurement of respiratory gas exchange is reasonable
to facilitate prescription of an appropriate exercise program for patients
presenting with HF. ARBs as an alternative to ACE inhibitors as first-line
therapy in patients with mild to moderate HF, particularly those already taking
an ARB for other indications. Digitalis in patients with current or prior
symptoms of HF to reduce hospitalization for HF. The addition of the
combination of hydralazine and a nitrate in patients with persistent symptoms
who are already taking an ACE inhibitor and beta blocker. CRT with or
without an ICD is reasonable in patients with an LVEF of 35 percent, a
QRS 0.12 seconds, and atrial fibrillation who have New York Heart
Association functional class III or ambulatory class IV symptoms symptoms
despite optimal chronic medical therapy. CRT is reasonable in patients with an
LVEF of 35 percent who have New York Heart Association functional class
III or ambulatory class IV symptoms despite optimal medical therapy and who
have frequent dependence of ventricular pacing.
CHF Systolic Dysfunction
• Class IIb - The weight of evidence and/or
opinion is less well established for the following
approaches in the management of patients with
current or prior symptoms of HF and a
reduced LVEF The combination of hydralazine
and a nitrate in patients who cannot be given an
ACE inhibitor or ARB because of drug
intolerance, hypotension, or renal
insufficiency. Addition of an ARB in patients with
persistent symptoms who are already being treated
with an ACE inhibitor, beta blocker, and diuretics
CHF Systolic Dysfunction
• Class III - There is evidence and/or general agreement
that the following approaches are not effective and may
be harmful in the management of patients with current
or prior symptoms of HF and a reduced LVEF Routine
use of triple therapy with an ACE inhibitor, an ARB, and
an aldosterone receptor antagonist is not
recommended. Routine administration of calcium channel
blockers are not indicated. Long-term infusion of a positive
inotropic drug may be harmful and is not recommended,
except as palliation for end-stage disease that cannot be
stabilized with standard medical therapy. Nutritional
supplements are not indicated. Hormonal therapies may be
harmful and are not recommended unless given to replete
hormone deficiencies.
Recommended following sequence of drugs
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Recommended following sequence of drugs in the typical patient, with allowance for variations
depending upon clinical response:
Loop diuretics are introduced first for fluid control in patients in overt HF. The goal is relief of signs
or symptoms of volume overload, such as dyspnea and peripheral edema.
ACE inhibitors, or if not tolerated, angiotensin II receptor blockers (ARBs) are typically initiated
during or after the optimization of diuretic therapy. These drugs are usually started at low doses and
then titrated to goals based upon trial data. (See "ACE inhibitors" belowSee "ACE inhibitors"
below).
Beta blockers are initiated after the patient is stable on ACE inhibitors, again beginning at low doses
with titration to trial goals as tolerated. (See "Beta blockers" belowSee "Beta blockers" below).
The following drugs should be given to selected patients in the absence of a contraindication:
The addition of the combination of hydralazine and a nitrate for patients (particularly blacks) with a
reduced LVEF who have persistent symptoms despite therapy with an ACE inhibitor and beta
blocker. (See "Hydralazine plus nitrates" below).
The addition of an aldosterone antagonist (spironolactone or, if not tolerated, eplerenone) to improve
survival in patients with New York Heart Association (NYHA) class III/IV symptoms (show table 4)
and a reduced left ventricular ejection fraction who can be monitored for preserved renal function and
a normal plasma potassium concentration. Aldosterone antagonists also may be used to assist in the
management of diuretic-induced hypokalemia (plasma potassium ≤3.8 meq/L) in patients with mildto-moderate HF. (See "Aldosterone antagonists" below).
Angiotensin II receptor blockers (ARBs) as an alternative to ACE inhibitors in patients who cannot
tolerate these drugs; the addition of an ARB to an ACE inhibitor may be considered in patients who
are persistently symptomatic and have a reduced left ventricular ejection fraction despite being
treated with conventional therapy. (See "Angiotensin II receptor blockers" below).
Digoxin to reduce hospitalization for HF or for patients with concomitant atrial fibrillation, for rate
control .
ACE inhibitors or beta blockers first
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The administration of ACE inhibitors before beta blockers is largely based upon clinical trials with
ACE inhibitors being performed before trials of beta blockers. Subsequent randomized trials (eg,
CIBIS III) suggest that the outcomes may be similar if beta blockers are given first [16-18].
The approach we recommend is based upon the differences in time to benefit and the importance of
attaining target dose between these two drug classes:
ACE inhibitors provide rapid hemodynamic benefit and will not exacerbate heart failure in the short
run [1]. (See "ACE inhibitors in heart failure due to systolic dysfunction: Therapeutic use", section
on Effect of dose).
The hemodynamic benefits of beta blockers are delayed (and there may be a transient worsening in
cardiac function when therapy is initiated), but the long-term improvements in left ventricular
ejection fraction (LVEF) and survival are dose-dependent in patients who can tolerate the target dose
(show figure 1) [19]. However, patients who cannot tolerate the target dose may derive similar
benefit as those who can, if they attain the same degree of beta blockade, as assessed from the
reduction in heart rate [20]. These observations suggest that some patients have higher sensitivity to
beta blockers.
Given these considerations, we start with a low dose of an ACE inhibitor (eg, lisinopril 5 mg/day),
increase to a moderate dose (eg, lisinopril 15 to 20 mg/day) at one to two week intervals, and then
begin a beta blocker, gradually increasing toward the target dose or, if this cannot be achieved, the
highest tolerated dose. When the beta blocker titration is completed, the ACE inhibitor titration is
completed. In patients with low risk of adverse response to ACE inhibitors (good blood pressure, no
hyponatremia, hyperkalemia or risk of intravascular depletion), higher doses of the ACE inhibitor can
be started and the titration can be quicker.
Complications that develop during dose titration should be treated. For example, increasing the
diuretic dose for fluid overload [1]. Hypotension rarely limits metoprolol titration, but may occur
with carvedilol due to its additional vasodilator activity. If hypotension limits carvedilol titration, one
should consider a change to metoprolol.
Since many patients with HF have low blood pressures, we generally alter the regimen only for
symptoms or signs of underperfusion. A cardiologist should be consulted in patients who have
difficulty attaining target doses.
ACE inhibitors
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ACE inhibitors improve survival in patients with all severities of myocardial disease,
ranging from asymptomatic left ventricular dysfunction [21] to moderate or severe HF
(show figure 2A-2C) [22-25]. However, there is some concern about their effectiveness
in blacks (show figure 3) [26-28]. (See "ACE inhibitors in heart failure due to systolic
dysfunction: Therapeutic use" and see "Influence of race" below).
All patients with asymptomatic or symptomatic left ventricular dysfunction should be
started on an ACE inhibitor. Beginning therapy with low doses (eg, 2.5 mg
of enalapril twice daily, 6.25 mg of captoprilthree times daily, or 5 mg of lisinopril once
daily) will reduce the likelihood of hypotension and azotemia [29]. If initial therapy is
tolerated, the dose is then gradually increased at one to two week intervals to, if
tolerated, a target dose of 20 mg twice daily of enalapril, 50 mg three times daily of
captopril, or up to 40 mg/day of lisinopril orquinapril. Blood should be obtained in all
patients one to two weeks after starting or changing a dose and periodically thereafter to
assess the plasma potassium concentration and renal function.
These relatively high doses are recommended because they were used in the successful
trials [1]. Although there is uncertainty if these doses are much more beneficial than
lower doses, maximum dose therapy, if tolerated, is still recommended [1,30,31]. If the
target doses cannot be administered or are poorly tolerated, lower doses should be used
with the expectation that there are likely to be only small differences in efficacy
between low and high doses [1,30]. (See "ACE inhibitors in heart failure due to systolic
dysfunction: Therapeutic use", section on Effect of dose).
Angiotensin II receptor blockers
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ARBs for the treatment of HF appear to be as or possibly slightly less effective than ACE inhibitors when compared
directly [32,33]. The CHARM-Alternative trial demonstrated benefit from candesartan in patients with class II or III
HF who could not tolerate ACE inhibitors, primarily because of cough [34].
The 2005 ACC/AHA task force recommended an ARB in patients who cannot tolerate ACE inhibitors for this use and
a class IIa recommendation for the use of an ARB as an alternative to ACE inhibitors, particularly in patients already
taking an ARB for another indication (show table 2) [1]. ARBs are more expensive than ACE inhibitors. (See
"Angiotensin II receptor blockers in heart failure due to systolic dysfunction: Therapeutic use").
A separate issue, the value of adding an ARB to appropriate doses of an ACE inhibitor, was confirmed in the
CHARM-Added trial [35]. The benefit of combination therapy was also seen in a variety of subgroups including
patients also treated with a beta blocker. This is an important observation since adding an ARB to an ACE inhibitor in
patients treated with a beta blocker appeared to be associated with increased mortality in a post hoc subgroup analysis
from the Val-HeFT trial (show figure 4) [36].
We regard the CHARM-Added data as more definitive for several reasons:
The benefits of ARBs in CHARM-Added were seen in the primary end point analysis, rather than in a post hoc
analysis as in the Val-HeFT
The duration of follow-up was longer in CHARM-Added (41 months versus 2 years)
A greater proportion of patients in CHARM-Added were treated with a beta blocker
In addition, significant benefit was also seen in the subset of 529 patients who met the United States Food and Drug
Administration (FDA) criteria for being on maximum doses of an ACE inhibitor at baseline, suggesting that similar
effects could not have been achieved by increasing the dose of the ACE inhibitor [37].
The 2005 ACC/AHA guidelines concluded that the weight of evidence was less well established (class IIb) (show
table 2) and the 2008 European Society of Cardiology guidelines concluded that evidence and/or general agreement
supported effectiveness (class Ia) for the addition of an ARB in persistently symptomatic patients with a reduced
LVEF who are already being treated with conventional therapy [1,3].
We suggest the addition of an ARB, if tolerated, to HF therapy in patients who are still symptomatic on ACE
inhibitors and beta blockers or are hypertensive. In patients with renal dysfunction or hyperkalemia, the addition of an
ARB must be done with caution.
However, based upon the VALIANT trial, which found no increase in efficacy with the combination of valsartan and
an ACE inhibitor, with or without a beta blocker in patients with HF who had had an acute MI within the preceding
10 days [38], an ARB should NOT be added to an ACE inhibitor in the immediate post-MI setting. (See "Angiotensin
converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Clinical trials").
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Beta blockers
At least certain beta blockers, particularly carvedilol,metoprolol succinate,
and bisoprolol, improve overall and event-free survival in patients with New York Heart
Association (NYHA) class II to III HF (show table 4) [39-41] and probably in class IV
HF [42,43]. Beta blockers with intrinsic sympathomimetic activity (such
as pindolol andacebutolol) should be avoided [39]. (See "Rationale for and clinical trials
of beta blockers in heart failure due to systolic dysfunction").
The beta blocker trials in HF were carried out in patients receiving therapy with an ACE
inhibitor; thus, the improvement in survival is additive to that induced by ACE
inhibitors (show figure 5) [44,45].
The magnitude of benefit was illustrated in a meta-analysis that included 22 trials
involving more than 10,000 patients [39]. Compared to placebo, beta blockers
significantly reduced mortality at one year (odds ratio 0.65) and two years (odds ratio
0.72). During the first year, it was estimated that beta blocker therapy saved 3.8 lives per
100 patients treated and was associated with four fewer hospitalizations per 100 patients
treated.
The controlled trials, which evaluated the role of beta blockers in HF, excluded patients
with relative contraindications to beta blocker therapy. Relative contraindications in
patients with HF include:
- Heart rate <60 bpm
- Symptomatic hypotension
- Greater than minimal evidence of fluid retention
- Signs of peripheral hypoperfusion
- PR interval >0.24 sec
- Second- or third-degree atrioventricular block
- History of asthma or reactive airways
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Choice of agent
We recommend use of carvedilol, bisoprolol or extended release metoprolol succinate since these
beta blockers have been shown to reduce all-cause mortality and decrease hospitalization in patients
with HF and left ventricular systolic dysfunction (LVEF ≤ 35-40 percent) in randomized controlled
trials.
Limited data are available on the comparative efficacy of these three beta blockers. Indirect evidence
suggests that carvedilol may produce greater improvement in LVEF than metoprolol. Patients with
low blood pressure may be less likely to tolerate carvedilol because of its vasodilatory activity.
Conversely, carvedilol may be preferred in patients with higher blood pressure. (See "Rationale for
and clinical trials of beta blockers in heart failure due to systolic dysfunction"section on Comparison
with other beta blockers.)
Retrospective data suggest that some beta blockers other than those with proven benefit in
randomized trials (eg, atenolol but not short-acting metoprolol tartrate) may be beneficial in HF.
However these observations are not sufficient to support a recommendation for use of beta blockers
without benefit established by randomized studies.
Patients with low blood pressure may tolerate metoprolol better thancarvedilol. Conversely, those
with high blood pressure may have a greater lowering of blood pressure with carvedilol. In MERITHF, metoprolol succinate resulted in a higher blood pressure than placebo, presumably because of
improved cardiac function.
Guidelines and recommendation — The ACC/AHA guidelines recommend use of one of the beta
blockers proven to reduce mortality (carvedilol, extended release metoprolol succinate,
and bisoprolol) in all stable patients with current or prior symptoms of HF and reduced LVEF, unless
contraindicated (show table 2) [1]. The 2006 HFSA guidelines included a similar recommendation
for patients with HF and LVEF ≤40 percent [7]. (See "Use of beta blockers in heart failure due to
systolic dysfunction").
In the absence of a contraindication, our recommendation is to offercarvedilol, metoprolol succinate,
or bisoprolol to patients with NYHA class II, III, or stable class IV HF with left ventricular ejection
fraction less than 40 percent.
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Initiation of therapy
Because of the need for careful attention to initial dosing and the risk of transient worsening of symptoms, it is
recommended that beta blocker therapy be initiated under the consultative guidance of an experienced HF center.
Among inpatients, initiation of therapy prior to hospital discharge improves beta blocker use without an increase in
side effects or drug discontinuation [46]. Prior to initiation of therapy, the patient should have no or minimal evidence
of fluid retention and should not have required recent intravenous inotropic therapy.
The patient should be informed that beta blockers may lead to an increase in symptoms for 4 to 10 weeks before any
improvement is noted. Therapy should be begun at very low doses and the dose doubled every two weeks until the
target dose is reached or symptoms become limiting [47]. Initial and target doses are:
For carvedilol, 3.125 mg twice daily initially and 25 to 50 mg twice daily ultimately (the higher dose being used in
subjects over 85 kg)
For extended-release metoprolol (metoprolol succinate), 12.5 mg daily in patients with NYHA class III or IV or 25
mg daily in patients with NYHA II, and ultimately 200 mg/day. If patients receive short acting metoprolol for cost
reasons, dosing is not well established, but we recommend 6.25 mg twice daily initially and 50 to 100 mg twice daily
ultimately.
For bisoprolol, 1.25 mg once daily initially and 5 to 10 mg once daily ultimately.
Even lower starting doses should be given to patients with recent decompensation or a systolic pressure below 85
mmHg.
Every effort should be made to achieve the target dose since the improvement appears to be dose-dependent. The
proportion of patients who reach the target dose is higher in clinical trials than in the general population in which the
patients are older and have more comorbid disease. However, although not optimal, even low doses appear to be of
benefit and should be used when higher doses are not tolerated [20].
What may be most important is the degree of beta blockade [20]. However, aiming for a particular resting heart rate
or a particular reduction in heart rate is not of proven value [48].
The patient should weigh himself or herself daily and call the physician if there has been a 1 to 1.5 kg weight gain.
Weight gain alone may be treated with diuretics, but resistant edema or more severe decompensation may require
dose reduction or cessation (possibly transient) of the beta blocker. (See "Use of beta blockers in heart failure due to
systolic dysfunction").
Although data about the duration of beta blocker therapy in HF are lacking, it has been suggested that patients who
are doing well should not have the beta blocker withdrawn, since clinical deterioration and sudden death or death
from progressive HF has been observed.
Digoxin —
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Digoxin is given to patients with HF and systolic dysfunction to control symptoms (such as fatigue,
dyspnea, and exercise intolerance) and, in patients with atrial fibrillation, to control the ventricular
rate. As demonstrated in the DIG trial, digoxin therapy was associated with a significant reduction in
hospitalization for HF but no benefit in terms of overall mortality [55].
However, subsequent subgroup analyses suggest that digoxin may have an effect on survival that
varies with the serum digoxin concentration (SDC). Compared to placebo, survival was significantly
improved when the SDC was between 0.5 and 0.8 ng/mL in men and significantly worsened when
the SDC was ≥1.2 ng/mL (show figure 7) [56]. A similar relationship was seen in women with a
nonsignificant trend toward improved survival when the SDC was between 0.5 and 0.9 ng/mL and
significantly worse survival when the SDC was ≥1.2 ng/mL [57]. (See "Use of digoxin in heart
failure due to systolic dysfunction", section on Optimal digoxin level).
The use of digoxin for the treatment of symptoms in patients with left ventricular dysfunction was
given a class I recommendation by 2005 ACC/AHA guidelines (show table 2) [1]. We recommend
starting digoxin in patients with left ventricular systolic dysfunction (left ventricular ejection fraction
[LVEF] <40 percent) who continue to have NYHA functional class II, III, and IV symptoms (show
table 4) despite appropriate therapy including an ACE inhibitor, beta blocker, and, if necessary for
fluid control, a diuretic. The usual daily dose is 0.125 mg or less, based upon renal function. Based
upon the data from the DIG trial mentioned above correlating serum digoxin concentration and
survival, we recommend maintaining the SDC between 0.5 and 0.8 ng/mL (show figure 7) [56].
Digoxin is NOT indicated as primary therapy for the stabilization of patients with acutely
decompensated HF. Such patients should first receive appropriate treatment for HF, usually with
intravenous medications. Digoxin may be initiated at the same time as part of a long-term treatment
strategy.
Diuretics
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Sodium and water retention lead to the common congestive symptoms of pulmonary and peripheral edema. Fluid
overload can typically be controlled and symptoms improved by diuretic therapy. Improvement in symptoms can
occur within hours to days. In comparison, the clinical effects of digoxin, ACE inhibitors, and beta blockers may
require weeks or months to become fully apparent.
Appropriate diuretic usage can also affect the success of other drugs given for the treatment of HF. Inappropriately
low doses will result in fluid retention, which can diminish the response to ACE inhibitors and ARBs and increase the
risk of decompensation with the use of beta blockers. Conversely, excessive diuresis will lead to volume contraction,
which can increase the risk of hypotension and renal insufficiency with ACE inhibitors, ARBs, and beta blockers.
A loop diuretic should be given to control pulmonary and/or peripheral edema. The most commonly used loop
diuretic for the treatment of HF is furosemide, but some patients respond better to bumetanide ortorsemide because of
superior and more predictable absorption. (See "Use of diuretics in heart failure").
The usual starting dose in outpatients with HF is 20 to 40 mg offurosemide or its equivalent. Subsequent dosing is
determined by the diuretic response. In patients who are volume overloaded, a reasonable goal is weight reduction of
1.0 kg/day. If a patient does not respond, the diuretic dose should initially be increased to find the single effective
dose, rather than giving the same dose twice a day.
Intravenous diuretics (either as a bolus or a continuous infusion) are more potent than their equivalent oral doses, and
may be required for unstable or severe disease. Thiazide diuretics can be added for a synergistic effect. (See "Use of
diuretics in heart failure").
The fall in intracardiac filling pressure that results from diuretic-induced fluid removal may lower the cardiac output
via the Frank-Starling relationship. This effect is usually minor and does not interfere with therapy. However, an
otherwise unexplained rise in BUN and serum creatinine should be viewed as a sign of a potentially important
reduction in tissue perfusion. Further diuresis should be performed only with careful monitoring for signs and
symptoms attributable to hypoperfusion. (See "Use of diuretics in heart failure").
Over the long term, diuretic therapy should be maintained to prevent recurrent edema. In many cases, this adjustment
can be facilitated by having the patient record his or her weight each day and allowing him or her to make changes in
dose if the weight increases or decreases beyond a specified range.
Aldosterone antagonists
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Spironolactone and eplerenone, which compete with aldosterone for the mineralocorticoid receptor, prolong survival in selected patients with HF. The
endocrine side effects of spironolactone result from nonselective binding to androgen andprogesterone receptors; eplerenone has greater specificity for the
mineralocorticoid receptor and therefore has a lower incidence of endocrine side effects (1 versus 10 percent in the respective trials cited below). (See "Use of
diuretics in heart failure", section on Improved survival with aldosterone antagonism).
The 2005 ACC/AHA guidelines concluded that the weight of evidence is in favor of efficacy of an aldosterone antagonist (class IIa) in selected patients with
moderate to severe HF and reduced LVEF who can be carefully monitored for preserved renal function and a normal plasma potassium concentration (show
table 2) [1].
The role of aldosterone blockade in mild-to-moderate HF has not been defined and its use was not recommended in such patients [1]. One exception would be
in patients with mild-to-moderate HF who have diuretic-induced hypokalemia (plasma potassium ≤3.8 meq/L) that cannot be controlled with potassium
replacement.
The efficacy of an aldosterone antagonist in patients treated with both an ACE inhibitor and an ARB, as in CHARM-Added, is uncertain [35]. The 2005
ACC/AHA guidelines on chronic heart failure concluded that an aldosterone antagonist should not be used in such patients (show table 2) [1].
Despite these recommendations, spironolactone appears to be used more broadly, without regard to NYHA class, without optimization of background therapy
with an ACE inhibitor and beta blocker, and without appropriate follow-up [58]. Such use has been associated with an increased rate of complications.
Although eplerenone is associated with fewer endocrine side effects than spironolactone (1 versus 10 percent in the respective trials), this advantage must be
weighed against the marked difference in cost between the two drugs. It may be reasonable to begin with spironolactone (25 to 50 mg/day), and switch to
eplerenone (25 and after four weeks 50 mg/day) if endocrine side effects occur. To the degree that blockade of a deleterious effect of aldosterone on the heart
is important, a similar benefit would not be expected with other potassium-sparing diuretics (such as amiloride).
It is essential that serum potassium and creatinine be checked one to two weeks after starting spironolactone or eplerenone and periodically thereafter.
Patients with poor renal function are particularly at risk for hyperkalemia.
Life-threatening hyperkalemia can also occur in the setting of other risk factors. These include:
Increasing age
More severe HF
Diabetes mellitus
Underlying renal dysfunction
Volume depletion
Higher baseline plasma potassium concentration
Spironolactone dose ≥50 mg/day
Higher ACE inhibitor or angiotensin II receptor blocker dose
Combined use of ACE inhibitors and angiotensin II receptor blockers
Concomitant beta blocker use
Use of potassium supplements or potassium-containing saltsubstitutes
Use of nonsteroidal antiinflammatory drugs
Renal dysfunction, which is an important risk factor for hyperkalemia in this setting, may be underestimated by the serum creatinine concentration, especially
in elderly patients and other patients with reduced lean body mass in whom creatinine production is reduced. Formulas are available to estimate glomerular
filtration rate from a stable serum creatinine that take into account age and body mass. (See "Assessment of kidney function: Serum creatinine; BUN; and
GFR", section on Estimation equations).
The treatment of HF due
to diastolic dysfunction
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TREATMENT — The treatment of HF due to diastolic dysfunction remains empiric, since trial data are limited.
General principles — Guidelines for treatment of patients with DHF were published in 2005 by the ACC/AHA task force on
chronic HF (show table 2) [13]. It was concluded that the weight of evidence supported only four modalities:
Control of systolic and diastolic hypertension
Control of ventricular rate in patients with atrial fibrillation
Control of pulmonary congestion and peripheral edema with diuretics
Coronary revascularization in patients with CHD in whom ischemia is judged to have an adverse effect on diastolic function
A clinical practice review concurred with the ACC/AHA guidelines and provided specific examples of clinical therapies
appropriate to achieving these goals (show table 3A-3B) [2].
Choice of medications — The choice of medications in patients with diastolic dysfunction is determined by two factors:
Treatment of specific underlying processes such as hypertension or symptomatic CHD. Combined therapy may be warranted
since hypertrophied hearts are more sensitive to the deleterious effects of ischemia on LV relaxation than nonhypertrophied hearts
[14]. (See "Pathophysiology of diastolic heart failure").
The possibly beneficial effect of the drug on the pathophysiology of DHF.
The guidelines concluded that efficacy was less well established for the administration of specific drugs, such as beta blockers,
angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and calcium channel blockers [13].
An important caveat is that the patient who has LV diastolic dysfunction with a small, stiff left ventricular chamber is particularly
susceptible to excessive preload reduction, which can lead sequentially to underfilling of the LV, a fall in cardiac output, and
hypotension. In patients with severe left ventricular hypertrophy (LVH) due to hypertension or hypertrophic cardiomyopathy,
excessive preload reduction can also create subaortic outflow obstruction.
For these reasons, the administration of diuretics or venodilators such as nitrates, dihydropyridine calcium channel blockers, and
ACE inhibitors must be performed with caution. Careful attention is required for symptoms of ventricular underfilling such as
weakness, dizziness, near syncope, and syncope.
Digoxin is generally NOT used in patients with DHF because contractility is intact. The DIG ancillary trial, a parallel study to the
DIG trial, evaluated the role of digoxin in patients with HF and an LVEF >45 percent [15,16]. At a mean follow-up of 37 months,
digoxin had no effect on all-cause or cause-specific mortality, or all-cause or cardiovascular hospitalization [15]. (See "Use of
digoxin in heart failure due to systolic dysfunction").
For long-term therapy, the most
effective control of heart rate in
atrial fibrillation, both at rest and
with exercise, occurs with which
one of the following?
A. Digitalis
B. Beta-adrenergic blockers
C. Calcium channel blockers
D. Class 1A antiarrhythmics
Answer
• B. Beta-adrenergic blockers
Explanation: For long-term therapy, betaadrenergic antagonist drugs provide the most
effective control of heart rate in atrial fibrillation,
both at rest and during exercise. Although calcium
channel blockers also lower heart rate both at rest
and with exercise, they are not as effective as betablockers. Digitalis is primarily effective in
controlling the heart rate at rest, and often does not
adequately control heart rate with exercise. The
Class 1 antiarrhythmics are most useful in
maintaining sinus rhythm and, in fact, may
paradoxically increase heart rate. Ref: Lampert R,
Ezekowitz MD: Management of arrhythmias. Clin
Geriatr Med 2000;16(3):593-618.