Session 25-Pharmacotherapy of Heart Failure

PST 06106
Basic Pharmacotherapy
Session 25: Pharmacotherapy of Heart Failure
Learning Objectives
By the end of this session students are expected to be able to:
• Define heart failure
• Explain pathophysiology of heart failure
• Explain the clinical presentation of heart failure
• Outline diagnosis of heart failure
• Describe pharmacological treatment of heart failure
• Describe the monitoring of heart failure therapy
Activity: Buzzing
 What is Heart Failure?
Definition of Heart Failure
• Heart failure is a progressive clinical syndrome that can result from any abnormality in
cardiac structure or function that impairs the ability of the ventricle to fill with or eject
blood, thus rendering the heart unable to pump blood at a rate sufficient to meet the
metabolic demands of the body.
• It is the final common pathway for numerous cardiac disorders, including those
affecting the pericardium, heart valves, and myocardium.
• Diseases that adversely affect ventricular diastole (filling), ventricular
systol(Contraction), or both can lead to heart failure
• Heart Failure is characterized by typical symptoms (e.g. breathlessness, ankle swelling
and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure,
pulmonary crackles and peripheral oedema) caused by a structural and/or functional
cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac
pressures at rest or during stress
Definition of Heart Failure Cont…
• Heart Failure is characterized by typical symptoms (e.g. breathlessness,
ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated
jugular venous pressure, pulmonary crackles and peripheral oedema) caused
by a structural and/or functional cardiac abnormality, resulting in a reduced
cardiac output and/or elevated intracardiac pressures at rest or during stress
• Heart failure can result from any disorder that affects the ability of the
heart to contract (systolic function) and/or relax (diastolic dysfunction)
• Therefore, Heart Failure can be;
• Systolic Heart Failure or/and
• Diastolic Heart Failure
Definition of Heart Failure Cont…
• Heart failure with impaired systolic function (i.e., reduced LVEF) is
the classic, more familiar form of the disorder
• LVEF (Left ventricular ejection fraction
Common Cause Of Heart Failure
Pathophysiology of Heart Failure
• Key components of the pathophysiology of cardiac remodeling are.
• Myocardial injury (e.g., myocardial infarction) results in the activation
of a number of hemodynamic and neurohormonal compensatory
responses in an attempt to maintain circulatory homeostasis.
• Chronic activation of the neurohormonal systems results in a cascade of
events that affect the myocardium at the molecular and cellular levels.
• These events lead to the changes in ventricular size, shape, structure,
and function known as ventricular remodeling.
• The alterations in ventricular function result in further deterioration in
cardiac systolic and diastolic function, which further promotes the
remodeling process. (LV left ventricular)
Pathophysiology of Heart Failure Cont….
Clinical presentation and diagnosis of HF
General
• Patient presentation may range from asymptomatic to cardiogenic shock.
Symptoms
• Dyspnea, (Shortness of breath)
• Orthopnea (Discomfort when breathed)
• Paroxysmal nocturnal dyspnea (an attack of severe shortness of breath
and coughing that generally occur at night)
• Exercise intolerance
• Tachypnea (Fast breathing)
Cont.....
Symptoms…..
• Cough
• Fatigue (feeling overtired)
• Nocturia (Frequent urination)
• Hemoptysis (Coughing up blood)
• Abdominal pain
• Anorexia
• Nausea
• Bloating (Build up of gas in the stomach and intestine)
• Poor appetite, early satiety
• Ascites (Abnominal swelling)
• Mental status changes
Cont.....
Signs
• Pulmonary rales (Abnormal lung sound)
• Pulmonary edema
• Cool extremities
• Pleural effusion (build up of fluids between the tissue that line the
lungs and the chest)
• Tachycardia (Fast heart rate)
• Narrow pulse pressure
Cont.....
Signs…….
• Cardiomegaly
• Peripheral edema
• Hepatojugular reflux (test for measuring jugular venous pressure
through the distention of the internal jugular vein)
• Hepatomegaly
Cont.....
Laboratory Tests
• Electrocardiogram may be normal, or it could show numerous
abnormalities, including acute ST-T wave changes from myocardial
ischemia, atrial fibrillation, bradycardia, and left ventricular
hypertrophy.
• Serum creatinine may be increased due to hypo perfusion.
• Preexisting renal dysfunction can contribute to volume overload.
• Complete blood count (CBC) can be useful in determining if heart
failure is due to a reduced oxygen-carrying capacity.
Cont.....
Laboratory Tests…
• Chest x-ray: useful for detecting cardiac enlargement, pulmonary
edema, and pleural effusions
• Echocardiogram: used to assess the size of the left ventricle, valve
function, pericardial effusion, wall motion abnormalities, and ejection
fraction
• Hyponatremia: serum sodium <130 mEq/L is associated with reduced
survival and may indicate worsening volume overload and/or disease
progression
Activity: Small Group Discussion
• What is the treatment of Heart Failure??
Pharmacological Treatment of Heart Failure
• Treatment of Heart Failure of depends on the stage of the Disease
• There are four identified stages of heart failure, and their treatment
recommendations
• Unless contraindicated, all patients with HF-REF(reduced ejection
fraction) should be started on an ACE inhibitor and a beta blocker (and a
diuretic, in most cases).
• No patient should receive three drugs which block the renin-angiotensin-
aldosterone system as hyperkalaemia and renal dysfunction will be
common.
• The safety and efficacy of combining an ACE inhibitor, an ARB and
MRA is uncertain and the use of these three drugs together is not
recommended
Functional Classification of Heart Failure
Treatment allogarism of Heart failure according to functional stage of Heart Failure
Cont….
Beta Blockers
• A meta-analysis confirms that beta blockers also reduce mortality in
patients with diabetes and HF
• All patients with heart failure with reduced ejection fraction,class II-
IV, should be started on beta blocker therapy as soon as their condition
is stable.
• Bisoprolol, carvedilol or nebivolol should be the first choice of beta
blocker for the treatment of patients with heart failure with reduced
ejection fraction.
• If beta blockers are contraindicated consider using ivabradine
Pharmacological Treatment of Heart Failure Cont….
Angiotensin-Converting Enzyme Inhibitors

• Patients with heart failure with reduced ejection fraction of all NYHA
functional classes, should be given angiotensin-converting enzyme
inhibitors.
• Important adverse effects are cough, hypotension, renal impairment and
hyperkalaemia.
• A key but rare adverse effect, which can be life threatening (due to
laryngeal involvement), is angioedema.
• Any patient who experiences angioedema should have the ACE inhibitor
withdrawn immediately and be prescribed an alternative agent.
Cont.….
Angiotensin Receptor Blockers
• Angiotensin II type 1 receptor blockers (ARBs) block the biological effect of
angiotensin II.
• Unlike ACE inhibitors they do not produce cough as a side effect and should
be used in patients who cannot tolerate an ACE inhibitor due to cough.
• Patients with heart failure with reduced ejection fraction, NYHA class II-IV,
who are intolerant of angiotensin-converting enzyme inhibitors should be
given an angiotensin receptor blocker.
• An angiotensin receptor blocker in addition to an angiotensin-converting
enzyme inhibitor should be considered in patients with heart failure with
reduced ejection fraction NYHA class II-IV, who are unable to tolerate a
mineralocorticoid receptor antagonist.
Cont.….
Mineralocorticoid Receptor Antagonists
• Patients with heart failure with reduced ejection fraction who
have ongoing symptoms of heart failure, NYHA class II-IV, LVEF
≤35%, despite optimal treatment, should be given mineralocorticoid
receptor anatgonists unless contraindicated by the presence of renal
impairment (chronic kidney disease stage ≥4–5) and/or elevated serum
potassium concentration (K+ >5.0 mmol/l).
• Eplerenone can be substituted for spironolactone in patients who
develop gynaecomastia.
Cont.….
Angiotensin Receptor/Neprilysin Inhibitors
• Patients with heart failure with reduced ejection fraction who have ongoing
symptoms of heart failure, NYHA class II-III, LVEF ≤40% despite optimal
treatment should be given sacubitril/valsartan instead of their ACE inhibitor
or ARB, unless contraindicated.
• It may be considered in patients with NYHA class IV symptoms.
• If the patient is already on an ACE inhibitor, the ACE inhibitor should be
stopped for 36 hours before initiating sacubitril/valsartan to minimise the risk
of angioedema.
• Patients should be seen by a heart failure specialist with access to a
multidisciplinary heart failure team before starting treatment with
sacubitril/valsartan
Cont.….
Diuretics/ Loop Diuretics
• In the majority of patients with heart failure fluid retention occurs,
causing ankle oedema, pulmonary oedema or both, contributing to the
symptom of dyspnoea.
• Diuretic treatment relieves oedema and dyspnoea.
• Patients with heart failure and clinical signs or symptoms of fluid
overload or congestion should be considered for diuretic therapy.
• The tendency of loop diuretics to cause hypokalaemia is offset by
ACE inhibitors, ARBs and spironolactone.
Cont.….
Diuretics/ Loop Diuretics …
• Care should be taken to select the dose of the loop diuretic on an
individual basis, so that the dose chosen or reached should eliminate
ankle or pulmonary oedema without dehydrating the patient and placing
them at risk of renal dysfunction or hypotension.
• Serum potassium should be monitored to maintain its concentration in
the range 4–5 mmol/l and adjustments in therapy should be made to
prevent both hypokalaemia and hyperkalaemia.
• The dose of diuretic should be individualised to reduce fluid retention
without overtreating which may cause dehydration or renal dysfunction.
Cont.….
Digoxin
• Digoxin is usually only reserved for patients with severe HF who have
not responded to other treatment
• In patients with HF and sinus rhythm, digoxin may reduce symptoms
and hospital admission
• Digoxin should be considered as an add-on therapy for patients with
heart failure in sinus rhythm who are still symptomatic after optimum
therapy.
• If excessive bradycardia occurs with concurrent beta blockade and
digoxin therapy, digoxin should be stopped.
Cont.….
Hydralazine and Isosorbide Dinitrate
• The combination of hydralazine and isosorbide dinitrate (H-ISDN) was
shown to reduce mortality in patients with HF before ACE inhibitors
were introduced
• Patients who are intolerant of an angiotensin-converting enzyme inhibitor
and an angiotensin II receptor blocker due to renal dysfunction or
hyperkalaemia should be considered for treatment with a combination of
hydralazine and isosorbide dinitrate.
• Patients with heart failure with reduced ejection fraction, NYHA class III
or IV, should be given hydralazine and isosorbide dinitrate in addition to
standard therapy
Monitoring of Heart failure Therapy
• Monitoring parameters for patients with Heart Failure focuses on three
general areas:
• evaluation of functional capacity,
• evaluation of volume status, and
• Laboratory evaluation.
• Assessment of volume status is a vital component of the ongoing care
of patients with heart failure.
• This evaluation provides the clinician important information about the
adequacy of diuretic therapy.
Monitoring of Heart failure Therapy Cont...
• Because the cardinal signs and symptoms of heart failure are caused
by excess fluid retention, the efficacy of diuretic treatment is readily
evaluated by the disappearance of these signs and symptoms.
• The physical examination is the primary method for the evaluation of
fluid retention, and specific attention should be focused on;
• the patient’s body weight,
• extent of jugular vein distention (JVD),
• presence and severity of pulmonary congestion and,
• Peripheral edema.
• Specifically, in a patient with pulmonary congestion, monitoring is
indicated for resolution of; rales and pulmonary edema and improvement
or resolution of dyspnea on exertion, orthopnea, and Paroxysmal
Nocturnal Dyspnea (PND).
• Other therapeutic outcomes include an improvement in exercise tolerance
and fatigue and a decrease in nocturia and heart rate.
• It should be noted that, particularly with β -blocker therapy, symptoms
may worsen initially and that it may take weeks to months of treatment
before patients notice improvement in symptoms.
• Routine monitoring of serum electrolytes and renal function is required in
patients with heart failure.
• Assessment of serum potassium is especially important because
hypokalemia is a common adverse effect of diuretic therapy and is
associated with an increased risk of arrhythmias and digoxin toxicity.
• Serum potassium monitoring is also required because of the risk of
hyperkalemia associated with ACE inhibitors, ARBs, and aldosterone
antagonists.
• A serum potassium ≥4 mEq/L should be maintained, with some
evidence suggesting it should be ≥4.5 mEq/L.
• Assessment of renal function (BUN and serum creatinine) is also an
important end point for monitoring diuretic and ACE inhibitor therapy
Key Points
• Heart Failure is characterized by typical symptoms (e.g. breathlessness, ankle
swelling and fatigue)
• Other signs of Heat Failure include elevated jugular venous pressure,
pulmonary crackles and peripheral oedema which are caused by a structural
and/or functional cardiac abnormality, resulting in a reduced cardiac output
and/or elevated intracardiac pressures at rest or during stress
• Treatment of Heart Failure of depends on the stage of the Disease
• Monitoring parameters for patients with Heart Failure focuses on three general
areas which are evaluation of functional capacity, evaluation of volume status,
and Laboratory evaluation
Evaluation
• What is Heart Failure?

• What is the pathophysiology of Heart Failure?
• What are the signs and symptoms of Heart Failure?
• How is the treatment of Heart Failure
References
• Wells BG, DiPiro J, Schwinghammer T (2013), Pharmacotherapy Handbook (6th
Ed). New York, NY: McGraw-Hill.
• DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach (7th ed): New York, NY: McGraw-
Hill.
• Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011) Principles
& Practice Study Guide: A Case-Based Care Plan Approach: New York, NY:
McGraw-Hill.
• Schwinghammer TL, Koehler JM (2009) Pharmacotherapy Casebook: A Patient-
Focused Approach (7th ed): New York, NY: McGraw-Hill.

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PST 06106

Angiotensin-Converting Enzyme Inhibitors

• What is Heart Failure?

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