Download HEART FAILURE WITH PRESERVED

16-1
HEART FAILURE WITH
PRESERVED EJECTION
FRACTION
1.b. What signs, symptoms, and other information indicate the
presence and severity of the patient’s HF?
• Signs: Peripheral edema, jugular venous distension, hepatojugular reflux, crackles in the right lung base, pulmonary effusion,
pulmonary edema, and cardiomegaly on CXR.
Joel C. Marrs, PharmD, FCCP, FASHP, FNLA,
BCPS-AQ Cardiology, BCACP, CLS
• Refer to corresponding textbook chapter for other signs and
symptoms of congestive heart failure (CHF).
Joseph P. Vande Griend, PharmD, FCCP, BCPS, CGP
• B-type natriuretic peptide (BNP) is a cardiac neurohormone
specifically secreted from the ventricles in response to volume
expansion and pressure overload. BNP levels are elevated in
patients with left ventricular (LV) dysfunction and have been
demonstrated to correlate with the New York Heart Association (NYHA) classification, as well as prognosis. They assist
clinicians in distinguishing CHF from other causes of dyspnea
such as COPD, asthma, or pneumonia. The symptoms may be
nonspecific, and physical findings are not sensitive enough to
use as a basis for an accurate diagnosis. In this particular case,
the elevated BNP levels suggest that the patient’s dyspnea is
possibly related to volume overload and LV dysfunction (BNP
>400 pg/mL indicates HF exacerbation 95% of the time).1
Multiple studies have shown that BNP measurements are a
sensitive and specific test to diagnose CHF in the emergency
department or urgent care setting.1
CASE SUMMARY
A 62-year-old man with a number of medical problems is hospitalized because of increasing dyspnea, weight gain, and pitting peripheral edema. A chest x-ray (CXR) shows evidence of heart failure
with preserved ejection fraction (HFpEF) with an echocardiogram
noting diastolic dysfunction and an EF of 53%. Patient management
requires up titration of diuretic therapy and optimization of the
patient’s current antihypertensive regimen. The patient is diuresed
with IV furosemide to reduce central venous pressure and an aldosterone antagonist is initiated with spironolactone. β-Adrenergic
blocker therapy with carvedilol and angiotensin converting enzyme
(ACE) inhibitor therapy with lisinopril are maintained to potentially reduce exacerbations of HF and to improve survivability
despite limited trial data to support their morbidity and mortality benefit in patients with HFpEF. With a history of myocardial
infarction, the patient warrants continuation of his β-blocker and
ACE inhibitor therapy. Isosorbide mononitrate was discontinued,
as it may not be as beneficial in the setting of HFpEF. Appropriate
patient education on the potential benefits and adverse effects of
this complex medical regimen is an important aspect of this case.
QUESTIONS
Problem Identification
1.a. Create a list of this patient’s drug-related problems.
• Symptomatic HFpEF: Not optimally managed with current
medications (including diuretic therapy, which is not yet optimized to maintain euvolemia). Regimen includes medications
that could potentially worsen or have no benefit in the diastolic
HF population (eg, isosorbide mononitrate).
• Hypertension: Inadequately treated to achieve/maintain
desired blood pressure (BP) goal.
• Type 2 diabetes mellitus (DM): A1C slightly above goal and
possible increased risk of lactic acidosis associated with continued use of metformin during acute exacerbation of HF.
• Coronary artery disease (CAD) with history of ST-segment
elevation myocardial infarction (STEMI): Secondary prevention currently includes treatment with a β-adrenergic blocker,
an ACE inhibitor, antiplatelet therapy, and a statin, but an
aldosterone antagonist is lacking from this regimen.
• Chronic obstructive pulmonary disease (COPD): Pharmacotherapy is not optimized with only as-needed medications. In
addition, the patient is receiving a nonselective β-adrenergic
blocker (carvedilol) that could potentially worsen the patient’s
• Cardiac troponin I (TnI) is a contractile protein present exclusively in cardiac muscle. In acute myocardial infarction (AMI),
TnI levels exhibit a rise and fall pattern similar to CK-MB. TnI
is more abundant in the myocardium than CK-MB and does
not normally circulate in the blood. TnI levels are detectable
3–6 hours after the onset of chest pain and peak 12–16 hours
later. They can remain elevated for 4–9 days post-AMI. This
patient’s TnI levels were obtained to determine if his shortness of breath (ie, CHF) could be related to an acute cardiac
event. The level reported does not suggest that his symptoms
are a result of an AMI, but serial enzymes would be needed to
completely rule this out.
1.c. What are the classification and staging of HF for this patient
on presentation?
• Stage C HF (current or prior symptoms of HF associated
with underlying structural heart disease).2,3 The same staging
criteria are used whether a patient has HFpEF or heart failure
with reduced ejection fraction (HFrEF). The echocardiogram
demonstrates a preserved EF and Grade II, or moderate diastolic dysfunction.
✓HFpEF is often referred to as diastolic HF, or diastolic dysfunction. The diagnosis of HFpEF is challenging, but the
most recent guidelines define HFpEF as having an EF >50%
in the absence of noncardiac causes of symptoms suggestive
of HF.2
✓Echocardiographically, there are four basic grading patterns
of diastolic HF (graded I–IV). Grade I diastolic dysfunction
is the mildest form and is associated with an abnormal relaxation pattern. Grade II diastolic dysfunction demonstrates
pseudonormal filling dynamics, is associated with elevated
left atrial filling pressures, and is considered moderate
diastolic dysfunction. Patients with Grade II diastolic dysfunction more commonly have symptoms of HF and may
demonstrate left atrial enlargement secondary to the elevated
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Heart Failure with Preserved Ejection Fraction
A Balancing Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Level II
• Symptoms: Increasing dyspnea on exertion, dyspnea at rest,
15-lb weight gain since last primary care physician (PCP)
appointment, exercise intolerance, and tachypnea.
CHAPTER 16
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COPD and, therefore, should be monitored especially during
dose titration.
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SECTION 2
pressures in the left heart. Grades III and IV diastolic dysfunction are restrictive filling patterns and are severe forms of
diastolic dysfunction. These patients tend to have advanced
HF symptoms. Grade III diastolic dysfunction patients
demonstrate reversibility of diastolic abnormalities on echocardiogram. In comparison, Grade IV diastolic dysfunction
patients do not have reversibility of these echocardiogram
abnormalities. Prognostically, the presence of Grade III or IV
diastolic dysfunction is associated with a significantly worse
prognosis. Patients with Grade III or IV diastolic dysfunction
will have left atrial enlargement, and a significant proportion
will have a reduced LV ejection fraction (LVEF), indicating a
combination of both systolic and diastolic dysfunction.
Cardiovascular Disorders
Grade
Hallmark Echocardiographic
Features
I
Abnormal relaxation pattern
II
Grade I with elevated left
atrial filling pressures; may
demonstrate left atrial
enlargement secondary to
the elevated pressures
Grade II with atrial enlargement; demonstrates
reversibility of diastolic
abnormalities
Grade II with atrial enlargement; demonstrates no
reversibility of diastolic
abnormalities
III
IV
Severity
Mild
severity
Moderate
severity
Notes
Commonly have
symptoms of
heart failure
COPD management is warranted to prevent confusion when
the patient has trouble breathing in determining whether it
is related to his COPD or his HF. Any breathing problems
need to be monitored during titration of his carvedilol, since
it is a nonselective β-blocker and can have negative respiratory consequences.
• CAD risk reduction pharmacotherapy is not optimized.
✓The patient is on a β-blocker, an ACE inhibitor, aspirin, and
a statin for secondary prevention, but his therapy could be
optimized with the addition of an aldosterone antagonist. In
addition, titration of his β-blocker is warranted in light of
both his CAD and his HFpEF, and this medication should
be titrated to achieve an optimal heart rate (HR).
• Refer to the corresponding textbook chapter for a list of drugs
that may precipitate HF.
Desired Outcome
2.a. What are the goals for the pharmacologic management of
HFpEF in this patient?
• Improve or resolve the patient’s symptoms.
Most severe
form
Most severe
form
May coexist with
HFrEF
May coexist with
HFrEF
• NYHA functional class IV.2,3
• Refer to the corresponding textbook chapter for a discussion of
the hemodynamic subsets of acute HF.
1.d.Could any of this patient’s problems have been caused by
drug therapy or lack of optimal drug therapy?
• HFpEF is not optimally managed.
✓ This patient has signs of fluid overload and needs his diuretic
therapy increased. There is no evidence to support the role of
nitrates (eg, isosorbide mononitrate) to manage HFpEF, but
they can be useful in patients with chronic angina (although,
this patient is not reporting symptoms of angina at this
time).
• The patient’s BP is not at goal.
✓In the setting of HFpEF, uncontrolled hypertension can
impair myocardial relaxation and promote cardiac hypertrophy. Thus, controlling this patient’s BP is essential. An additional BP-lowering agent (eg, an aldosterone antagonist),
as well as titration of the patient’s existing antihypertensive
medications, may be warranted.
• The patient’s A1C is not at the recommended goal of
<7% as per the American Diabetes Association guideline
recommendations.
✓Dose titration of the patient’s metformin to an optimal dose
of 1000 mg twice daily could be considered; however, at this
time, while the patient is experiencing an acute exacerbation
of HF, his metformin should be temporarily withheld.
• The patient is only on an as-needed therapy for his COPD and
should be placed on a chronic daily medication.
✓The patient’s COPD control can have a direct impact on
his HF status, specifically his respiratory function. Optimal
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
• Improve his exercise tolerance.
• Reduce the potential for morbidity and mortality.
• Avoid iatrogenic complications and maximize his quality of
life.
• Control hypertension (hypertension impairs myocardial relaxation and promotes cardiac hypertrophy).
• Reduce preload, but not too aggressively (reducing preload too
much may precipitate hypotension).
• Treat any underlying myocardial ischemia.
2.b.Considering this patient’s other medical problems, what
other treatment goals should be established?
• Establish BP control (goal BP of <140/90 mm Hg).3
• Maintain glycemic control to prevent end-organ damage
(ideally, A1C <7%).
• Assess the patient’s fasting lipid panel to establish whether
the patient has been adherent/responsive to his high intensity
statin therapy based on his established atherosclerotic cardiovascular disease (ASCVD).4
Therapeutic Alternatives
3.What medications are indicated in the long-term management
of this patient’s HFpEF based on his stage of HF?
• In comparison to the treatment of HFrEF, few clinical trials are
available to guide the management of patients with HFpEF. In
general, controlled studies have been performed with digitalis,
ACE inhibitors, angiotensin II receptor blockers, β-blockers,
calcium channel blockers, and aldosterone antagonists in
patients with HFpEF.5–10 However, these trials have been small
or have produced inconclusive results. When treating HFpEF,
attaining BP goals, controlling HR, and managing volume
overload are critical.2–4
• β-Blockers are useful in reducing BP, preventing ischemia,
promoting regression of ventricular hypertrophy, and slowing HR. There are extensive data in the HF with reduced
ejection fraction population showing improved mortality
and morbidity with the use of β-blockers. Findings from the
Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) revealed
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• Calcium channel blockers, particularly the nondihydropyridines (eg, verapamil and diltiazem), have some potential
beneficial effects on diastolic dysfunction in patients with left
ventricular hypertrophy (LVH) and hypertrophic cardiomyopathy, but their role in HFpEF is less clear.6 These agents
reduce BP and myocardial ischemia. In addition, they do promote regression of LVH and reduction in HR.
•
•
• Digoxin’s role in the management of patients with diastolic HF
has not been clearly defined. It may improve diastolic filling
in patients with HF and atrial fibrillation by slowing the ventricular rate, but its action on sodium–potassium ATPase may
lead to increased intracellular calcium and cause worsening of
ventricular relaxation.
• Aldosterone antagonist’s role in the management of patients
with HFpEF has been partially clarified, but there remains a
question of mortality impact. The Aldosterone Antagonist
Therapy for Adults with Heart Failure and Preserved Systolic
Function (TOPCAT) study evaluated the impact of spironolactone versus placebo on cardiovascular morbidity and mortality
over a 2-year study period in patients >50 years of age with
an ejection fraction >45%.10 No difference in the primary end
point (composite of CV death, aborted cardiac arrest, and hospitalization for HF) between the spironolactone and placebo
treatment arms was seen with an HR 0.89 (95% CI 0.77–1.04;
P = 0.14). The secondary end point of hospitalization for HF
resulted in a significant reduction with spironolactone versus
placebo with an HR 0.83 (95% CI 0.69–0.99; P = 0.04). There
has also been a sub-analysis of the TOPCAT study evaluating
differences in patients enrolled in the Americas compared
to Russia/Georgia relative to the primary and secondary end
points. When compared to those treated with placebo, patients
enrolled from North or South America had a significant reduction with spironolactone treatment in the primary end point
(HR 0.82 (95% CI 0.69–0.98) and all secondary end points.11
Based on these findings there is promise for the role of spironolactone as a treatment option to reduce hospitalizations
from HF and potentially CV death in patients with HFpEF.
Optimal Plan
4.What drugs, doses, schedules, and duration are best suited for
the management of this patient?
• IV diuretics (eg, IV furosemide, 80 mg) should be the initial
intervention to maintain adequate urine output and resolve
pulmonary congestion and its associated symptoms. The
ACCF/AHA 2013 Guidelines state that “hospitalized patients
with significant fluid overload should be treated with IV loop
•
•
Outcome Evaluation
5.What clinical and laboratory parameters are needed to evaluate the therapy for achievement of the desired therapeutic
outcome and to detect and prevent adverse events?
Efficacy parameters:
• BP should be monitored with the goal of normalizing systolic
and diastolic pressures.
• Fluid intake and urine output should be monitored daily during the acute initial stages of diuresis.
• The patient should be assessed for improvement in his exercise
tolerance.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Heart Failure with Preserved Ejection Fraction
• ACE inhibitors and angiotensin receptor blockers (ARBs) reduce
cardiac preload and afterload and improve myocardial relaxation and compliance. Improvements in LV filling and reduction in BP are associated with improved exercise tolerance and
quality of life.6 Data demonstrating beneficial effects of these
agents on mortality are limited. A retrospective trial involving ACE inhibitor therapy demonstrated improvements in
mortality,7 and data from one arm of the Candesartan in Heart
Failure Assessment of Reduction in Morbidity and Mortality
(CHARM) trial did not show a mortality benefit, but treatment with candesartan did reduce hospitalization rates.6 The
I-Preserve trial evaluated irbesartan versus placebo in HFpEF
patients and showed no significant reduction in morbidity or
mortality at a little over 4 years.6
diuretics. The initial dose should equal or exceed the patient’s
chronic oral daily dose.”2 Using the same dose of IV furosemide as the patient’s oral dose is essentially doubling the
dose (oral furosemide has an average bioavailability of 50%).
Doses can be doubled every 30–60 minutes until an adequate
response has been achieved. After resolution of pulmonary
congestion, switch the patient to chronic oral therapy, titrating
to slowly reestablish baseline weight and resolution of peripheral edema. Dose conversions from IV furosemide back to oral
furosemide need to be considered since the IV dose is twice as
potent as the oral dose. (eg, a 40-mg IV dose of furosemide is
equivalent to an 80-mg dose of oral furosemide.)
An ACE inhibitor is already on board and has been titrated
to a maximal tolerated dose without symptoms of hypotension or signs of hypoperfusion (eg, increased serum creatinine
[SCr] or reduced urine output). This treatment is necessary to
reduce the patient’s CV risk, not only secondary to his HF but
especially in light of his significant CAD history.
A β-blocker is already on board and should be titrated up
over many weeks to optimize the dose. There is no need to
acutely stop the β-blocker during this acute fluid overload
episode, because the episode was not related to a titration
of the β-blocker nor is the patient needing acute inotropic
therapy. The β-blocker should be titrated to maintain an
HR goal of 60 since tachycardia can contribute to HFpEF
secondary to decreased filling times and impairment of diastolic relaxation. The patient should be monitored for any
breathing problems occurring during dose titration since he
is on a nonselective β-blocker and has concurrent COPD. If
the patient experiences respiratory problems with carvedilol,
metoprolol is a potential alternative since it is a β1-selective
β-blocker. (It should be noted, however, that metoprolol may
lose its β1-selectivity at higher [optimal] HF doses. Further, the
impact of β-selectivity related to β-blocker use in patients with
COPD and HFrEF was recently evaluated in the OPTIMIZEHF study. The results of this retrospective analysis showed no
evidence that β-selectivity was associated with a difference in
outcomes among HF patients with and without COPD.12)
An aldosterone antagonist was initiated during the hospital
stay, but should be titrated to a target dose over the next
month. Assessment of the patient’s serum creatinine (SCr)
and serum potassium should be made prior to dose titration
and within 7 days of discharge. This treatment is necessary to
reduce the patient’s CV risk (eg, decrease in HF hospitalizations) with his HFpEF.
Isosorbide mononitrate should be discontinued, because there
are no data to support its role in the management of HFpEF.
The patient has not reported any angina-related chest pain.
However, if he does experience angina symptoms, a nitrate is a
reasonable agent to add to his β-blocker.
CHAPTER 16
significant mortality and morbidity reductions in the HFrEF
population but not in the HFpEF.8
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SECTION 2
• Body weight should be evaluated daily initially to assess the
efficacy of diuresis; the long-term goal is to return to his baseline body weight.
• The patient’s quality of life can be assessed using standard
scales.
Toxicity parameters:
• Monitor HR for bradycardia.
• Symptoms of hypotension (eg, light-headedness).
Cardiovascular Disorders
• Signs of hypotension (eg, rising blood urea nitrogen [BUN]/
SCr, decreasing urine output, tachycardia).
• Symptoms of hypovolemia (eg, light-headedness).
• Signs of hypovolemia (eg, hypotension and tachycardia); vital
signs should be measured frequently during the initial stages
of diuresis.
• Renal function tests (eg, BUN and SCr) should be assessed
daily initially to monitor for prerenal azotemia resulting from
over diuresis.
• Serum electrolytes, especially potassium and sodium, should
be monitored daily initially and then periodically thereafter
(within 7 days of dose initiation and following dose titration).
• Fasting lipid profiles, glucose, and A1C should be monitored
periodically.
• Monitor for worsening HF or worsening COPD with β-blocker
titration.
Patient Education
6.What information should be provided to the patient about the
medications used to treat his HFpEF?
General information:
• It is important for you to take each medication daily exactly
as prescribed and let your physician know if you are unable to
pick up any medications when discharged from the hospital.
• If you miss a dose, take it as soon as you remember, unless it is
almost time for your next dose.
• This medicine sometimes causes dizziness and lightheadedness, especially when getting up from the lying or sitting position.
• Contact your physician if you experience dry mouth and/or
increased thirst associated with decreased urine output, skin
rash, tingling or loss of hearing, irregular heartbeat, fever or
chills associated with sore throat, nausea and vomiting, or
mood changes.
• This medicine will need to be adjusted to maintain your fluid
balance and these adjustments will be based on the daily
weights you record.
Carvedilol:
• Carvedilol is in a class of drugs called β-blocking agents, or
β-blockers.
• Carvedilol is used to control BP, slow your HR, and reduce the
workload of the heart.
• This medication is to be taken twice daily.
• If you forget to take a dose, take it as soon as you remember. If
it is almost time for your next dose, skip the missed dose and
return to your regular schedule.
• This medicine may raise or lower your blood sugar, or it may
cover up symptoms of very low blood sugar (hypoglycemia).
Report any changes in your blood sugar to your physician.
• This medicine may make you dizzy or drowsy, but this effect
usually gets better over time. Avoid driving, using machines, or
doing anything else that could be dangerous if you are not alert.
Spironolactone:
• Spironolactone is in a class of drugs called aldosterone
antagonists. They are used to control BP and reduce symptoms
associated with diastolic HF.
• This medication can be taken by mouth once daily.
• Contact your physician if you notice any sudden changes in
your weight, exercise tolerance, shortness of breath, urine output, and overall sense of well-being.
• If you forget to take a dose, take it as soon as you remember. If
it is almost time for your next dose, skip the missed dose and
return to your regular schedule.
• It is advisable to weigh yourself daily and record these readings in a log.
• This medicine may cause dizziness, light-headedness, or fainting, especially during hot weather. Notify your physician if you
notice difficulty breathing or skin rash or itching.
• Check with your physician or pharmacist before starting any
new medications, including nonprescription remedies.
• Be sure to keep all follow-up appointments with your physician.
Lisinopril:
• Lisinopril is in a class of drugs called ACE inhibitors. They are
used to control BP and reduce the workload of the heart.
• This medication can be taken by mouth once daily.
• If you forget to take a dose, take it as soon as you remember. If
it is almost time for your next dose, skip the missed dose and
return to your regular schedule.
• This medicine may cause dizziness, light-headedness, or fainting,
especially during hot weather. Notify your physician if you notice
difficulty breathing; reduced urine output; swelling of the face,
lips, or tongue; a dry, persistent cough; or skin rash or itching.
Furosemide:
• This medicine has the potential to increase your potassium; so,
we will monitor your potassium level closely.
■■ FOLLOW-UP QUESTIONS
1.Outline a plan for maximizing the patient’s current medication regimen for HFpEF.
• Lisinopril should be maintained at current dosage if the
patient’s BP and renal function allow.
• Carvedilol dosage can be titrated if the patient’s HR and BP
are not at goal; since the patient weighs >85 kg, the maximum
dose would be 50 mg twice daily. During titration symptoms of
worsening HF and COPD should be monitored. If symptoms
of worsening HF or COPD occur, the dose should be reduced
or maintained at the current dose, and titrated only once the
patient is stable from an HF and COPD standpoint.
• Furosemide is a diuretic that is used to maintain appropriate
fluid balance in patients with HF.
• Furosemide dosage can be adjusted to manage the fluid balance
of the patient.
• You will notice an increase in the amount of urine or in your
frequency of urination.
• Spironolactone should be continued and titrated to 25 mg
daily in 2 weeks if the patient is able to tolerate the medication
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
16-5
2.Would you consider titrating up his carvedilol to a higher
dose? If so, why? Is switching the patient to a long-acting,
once-daily carvedilol product indicated?
• If the patient’s HR is still not at a target HR of 60 bpm,
carvedilol titration should occur at every 2-week interval
(doubling dose) until the patient reaches a dose of 50 mg twice
daily (as this dose has been tolerated in HF patients >85 kg).
REFERENCES
1. Tang WH, Francis GS, Morrow DA, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical
utilization of cardiac biomarker testing in heart failure. Circulation
2007;116:e99–e109.
2. Yancy C, Jessup M, Bozkurt B, et al. 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. Circulation 2013;128:e240–e327.
3.Lindenfeld J, Albert NM, Boehmer JP, et al. Executive summary:
HFSA 2010 comprehensive heart failure practice guideline. J Card Fail
2010;16:475–539.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Heart Failure with Preserved Ejection Fraction
• If nonadherence is an issue for the patient, then a once-daily
extended-release carvedilol may be an option, but this product
has not been studied in the HF population. This issue should
be addressed with all his medications by calling his pharmacy
and making sure he is picking up all his medications (especially his diuretic therapy since being fluid overloaded caused
his hospitalization).
4. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline
on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S1–S45.
5.The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med
1997;336:525–533.
6. Basaraba JE, Barry AR. Pharmacotherapy of heart failure with preserved ejection fraction. Pharmacotherapy 2015;35:351–360.
7. Nanaykkara S, Kaye DM. Management of heart failure with preserved
ejection fraction: a review. Clin Ther 2015;37:2186–2198.
8. Hernandez AF, Hammill BG, O’Connor CM, Schulman KA, Curtis
LH, Fonarow GC. Clinical effectiveness of beta-blockers in heart failure: findings from the OPTIMIZE-HF (organized program to initiate
lifesaving treatment in hospitalized patients with heart failure) registry.
J Am Coll Cardiol 2009;53:184–192.
9. Nichols GA, Reynolds K, Kimes TM, Rosales AG, Chan WW. Comparison of risk of re-hospitalization, all-cause mortality, and medical
care resource utilization in patyients with heart failure and preserved
versus reduced ejection fraction. Am J Cardiol 2015;116:1088–1092.
10. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure
with preserved ejection fraction. N Eng J Med 2014;370:1383–1392.
11.Pfeffer MA, Claggett B, Assmann SF, et al. Regional variation in
patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial.
Circulation 2015;131:34–42.
12. Mentz RJ, Wojdyla D, Fiuzat M, et al. Association of beta-blocker use
and selectivity with outcomes in patients with heart failure and chronic
obstructive pulmonary disease (from OPTIMIZE-HF). Am J Cardiol
2013;111:582–587.
CHAPTER 16
without hypotension, continues to have a serum potassium
<5.0 mEq/L, and maintains stable kidney function.