2-Heart Failure

Definition
• Heart failure (HF) is a condition caused by the inability of the heart to pump
sufficient blood to meet the metabolic needs of the body (1).

Classification
With systolic failure(problem in contraction): there is a decreased ejection of
blood from the heart during systole. With diastolic failure (problem in the filling
of ventricles), filling of the ventricles during diastole is reduced (2).

Etiology:
The common underlying etiologies in patients with heart failure are coronary artery
disease and hypertension (3).

Clinical Manifestations
A-Left-sided failure. If blood cannot be adequately pumped from the left ventricle
to the peripheral circulation, the blood will backs up into the pulmonary alveoli.
The result is the development of pulmonary congestion and edema (4).
Patients can experience a variety of symptoms [Dyspnea (difficult breathing), or
shortness of breath (SOB)], related to buildup of fluid in the lungs (5).
1-Exertional dyspnea occurs when patients describe breathlessness induced
by physical activity (5).
2-Orthopnea : Orthopnea is present if a patient is unable to breathe while
lying flat on a bed (i.e., in the recumbent position)(5).
3-Paroxysmal nocturnal dyspnea (PND)occurs when patients awaken
suddenly with a feeling of breathlessness and suffocation (5).

B-Right -sided failure.

When blood is not pumped from the right ventricle, the blood backs up throughout
the body producing systemic congestion and edema (4). Edema is especially
noticeable in the legs (ankles edema)because gravity pulls the fluid into the
lower half of the body (6).

Heart Failure Symptoms'

Classification
(table1)(7).

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Investigations
1-Echocardiogram: Used to assess LV size, and ejection fraction (EF) (the
fraction of the blood pushed during systole from the volume of blood that present
at the end of diastole : normally it is more than 50 %) (5).
2-Chest x-ray: Useful for detection of cardiac enlargement, pulmonary edema,
and pleural effusions (4).
3-ECG: To assesses the presence of any other cardiac problems, such as
arrhythmias (5, 8).

Treatment

Nonpharmacologic Interventions
Nonpharmacologic treatment involves:
1-Dietary modifications in HF consist of sodium restriction and sometimes fluid
restriction (5). Patients should routinely practice moderate salt restriction (2–2.5 g
sodium or 5–6 g salt per day) (9). Patients should be educated to avoid cooking with
salt and to limit intake of foods with high salt content (5). . Fluid restriction may not
be necessary in many patients. When applicable, a general recommendation is to
limit fluid intake from all sources to less than 2 liters per day (5).
2-Exercise, while discouraged when the patient is acutely decompensated (Acute
heart failure), is recommended when patients are stable. Regular low intensity,
aerobic exercise that includes walking, swimming, or riding a bike is encouraged,
while heavy weight training is discouraged (5). .
3-Modification of classic risk factors, such as tobacco and alcohol consumption,
is important to minimize the potential for further aggravation of heart function (5).

Pharmacologic Treatment
A-Systolic Heart Failure
Agents with proven benefits in improving symptoms, slowing disease
progression, and improving survival (reduce mortality) in chronic HF include:
ACE inhibitors, ARBs, β-adrenergic blockers (1), aldosterone antagonists (in
select patients) (1, 5) and most recently the combination of angiotensin-
receptor/neprilysin inhibitor (ARNI) [(sacubitril/valsartan (Entresto®)] (10).

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A-Neprilysin inhibitors (10).
1-Neprilysin is an enzyme that involved in degradation of many peptides including
natriuretic peptides, bradykinin and adrenomedullin. Inhibition of neprilysin
increased the availability of these peptides which exert favorable effects in heart
failure (e.g. vasodilatation and natriuretic actions).

2-Because neprilysin also degrades angiotensin II, a neprilysin inhibitor must

be combined with agent that blocks rennin-angiotensin system. Since ACE and
neprilysin each breakdown bradykinin, inhibiting both enzyme lead to significant
increase in the risk of angioedema. For that reason the neprilysin inhibitor-ARB
(Sacubitril/Valsartan) combination was developed.

3-The updated American College of Cardiology/American Heart Association

(ACC/AHA)guideline in 2016 recommend using an ACE inhibitor, ARB, or ARNI
in combination with background therapy, including beta-blockers and aldosterone
antagonists, to reduce morbidity and mortality.

4-For patients with chronic symptomatic class II or III HF with reduced ejection
fraction who tolerate an ACE inhibitor or ARB, the guidelines recommend
replacing the existing ACE inhibitor or ARB with an ARNI to reduce
morbidity and mortality.

B-Angiotensin-Converting Enzyme (ACE) Inhibitors:

1-The updated (ACC/AHA)guideline in 2016 recommend using an ACE inhibitor
(like captopril, lisinopril, enalapril,…..), ARB, or ARNI in combination with
background therapy, including beta-blockers and aldosterone antagonists, to reduce
morbidity and mortality (10).

2-ACE inhibitors should be initiated at low doses, followed by increments in dose

if lower doses have been well tolerated (9).

C-β-Blockers:
1-The ACC/AHA guidelines state that β-blockers should be prescribed to all
patients with stable systolic HF unless they have a C/I. Extended-release
metoprolol succinate, carvedilol, and bisoprolol are FDA approved for use in HF.
Metoprolol and bisoprolol are both partially selective β1-lockers, and carvedilol is
a mixed α1- and nonselective β-blocking agent (1).

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2- β-Blockers should be initiated in stable patients who have no or minimal
evidence of fluid overload. Because of their negative inotropic effects, β-blockers
should be started in very low doses with slow upward dose titration (1)(in a ‘start
low, go slow’ fashion) (11) to avoid symptomatic worsening (1).

D-Angiotensin II Receptor Blockers (ARBs):

Although some data suggest that ARBs produce equivalent mortality benefits when
compared with ACE inhibitors, the ACC/AHA guidelines recommend use of
ARBs only in patients who are intolerant of ACE inhibitors (1).

E-Aldosterone Antagonists:
There is evidence that aldosterone mediates some of the major effects of RAAS
activation, such as myocardial remodeling and fibrosis, as well as sodium
retention and potassium loss at the distal tubules (9).
Currently low-dose aldosterone antagonists (e.g. 25 mg/day spironolactone) should
be added for:
(1) Patients with symptoms of moderate to severe heart failure (NYHA class II-
IV) who are receiving standard therapy; and
(2) Those with LV dysfunction early after MI (where heart failure occurs in the
first 4 weeks after an acute myocardial infarction (1, 11)).
(3)in patients with a left ventricular ejection fraction ≤ 35%.(12).

F-Diuretics:
1-Loop and thiazide diuretics have not been shown to improve survival in
heart failure (11). Consequently, diuretic therapy (in addition to sodium
restriction) is recommended in all patients with clinical evidence of fluid
retention (peripheral and pulmonary edema) (1, 13). Patients who do not have fluid
retention would not require diuretic therapy (1).

2-Loop diuretics (furosemide, bumetanide, and torsemide) are the most

widely used diuretics in HF (5).

J-Nitrates and Hydralazine:

1-Nitrates (e.g., ISDN) and Hydralazine are combined in the treatment of HF
because of their complementary hemodynamic actions (1). Hydralazine is a potent
arterial dilating agent that decrease afterload. Nitrates have venous dilating
properties that decrease preload (14).

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2-The combination may be reasonable for patients with persistent symptoms
despite optimized therapy with an ACE inhibitor (or ARB) and β-blocker. The
combination also appropriate as first-line therapy in patients unable to tolerate
ACE inhibitors or ARBs (1).

H-Digoxin
1-Digoxin does not improve survival in patients with HF but does provide
symptomatic Benefits only (1) .

2-Current recommendations are for the addition of digoxin for patients who
remain symptomatic despite an optimal HF regimen consisting of an ACE
inhibitor or ARB, β-blocker, and diuretic (5).

3-Digoxin is also prescribed routinely in patients with HF and concurrent

atrial Fibrillation (AF) (14) to slow ventricular rate regardless of HF symptoms (2).

Ivabradine is approved by FDA for symptomatic chronic heart failure with left
ventricular ejection fraction ≤35%, with sinus rhythm and a heart rate of greater
than or equal to 70 bpm at rest to reduce the risk of hospitalization for worsening
HF in adults. (14).

B-Heart Failure Caused by Diastolic Dysfunction

Diastolic dysfunction, an inadequacy of ventricular relaxation and impaired LV
filling. Diastolic dysfunction is characterized by a normal or near-normal LVEF
(15)
(40% to 60%)(5). For symptomatic patients, diuretics in conjunction with salt
restriction are indicated initially to relieve congestive symptoms. Thereafter, β-
adrenergic blockers, calcium channel blockers (e.g., verapamil), or ACE
inhibitors, and ARBs, may be beneficial (15).

Note :
1-Unlike in systolic HF, nondihydropyridine calcium channel blockers (diltiazem
and verapamil) may be useful in heart failure caused by diastolic dysfunction (5).

2-A recent study did not find favorable effects with digoxin in patients with mild to
moderate diastolic HF. Therefore, the role of digoxin for symptom management
and HR control in these patients is not well established (5).

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Pulmonary edema(16).
Immediate treatment for acute pulmonary edema:
- Patient should be placed in the semisitting position to decrease venous return.
-Supplemental oxygen should be administered, mechanical ventilation is
indicated if oxygenation is inadequate or hypercapnia occurs.
-Morphine sulfate reduces anxiety and dilates pulmonary and systemic veins; 2-4
mg can be given intravenously over several minutes and can be repeated every 10-
25 minutes until an effect is seen.
-Furosemide is a venodilator that decreases pulmonary congestion within minutes
of IV administration, well before its diuretic action begins. An initial dose of 20-
80 -mg IV should be given over several minutes and can be increased based on
response.
- IV nitroglycerin or nitroprusside can be used if systolic BP is > I 00.
- inotropic drugs like dopamine or dobutamine in patients with concomitant
hypotension or shock. ( if systolic BP< 90).

References
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5- Marie A. Chisholm-Burns .Pharmacotherapy Principles & Practice. 4 rd edition. 2016. .
6-Campion Quinn.100 question and answers about congestive heart failure. Copyright © 2006
7- Angela R. Thomason. A Pharmacist’s Guide for Systolic Heart Failure. US Pharm. 2006;7:58-68.
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9-Maxine A.Papadakis ,Stephen J.Mcphee. Current Medical Diagnosis and Treatment . 58 th ed. 2019
10- Michael R. Updated Heart Failure Guidelines Highlight Role of Entresto, pharmacy times. 2016.
11- Abdallah Al-Mohammad, Jonathan Mant. The diagnosis and management of chronic heart failure: review
following the publication of the NICE guidelines. Heart 2011;97:411-416.
12-Lee Goldman,Andrew I. Schafer.Goldman- Cecil Medicine .25th Edition.
13 - Paul G. Schmitz and Kevin J. Martinl. Internal medicine just the facts. Copyright © 2008 .
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15- David J Quan, Richard A Helms. Textbook of Therapeutics: Drug and Disease Management. 8th edition.
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of Medical Therapeutics, The, 35 th Edition 2016.

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