Seminar presentation on

HEART FAILURE

By Ayantu Hassen
Beteley Abebe
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 Outline
• Introduction
• Epidemiology
• Etiology
• Pathophysiology
• Classification
• Clinical presentation/lab investigation
• Management
• Reference

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 Introduction

• Heart Failure: is a complex clinical syndrome caused by any

structural or functional cardiac disorder that impairs the ability of
the ventricle to fill with or eject blood.
• Heart failure is clinical state in which an abnormality of the heart
is responsible for its inability to fill with or eject blood at a rate
proportional to the requirements of the metabolizing tissues.

• Congestive Heart Failure(CHF): is a clinical syndrome

characterized by a history of specific signs and symptoms related
to congestion and hypoperfusion

• HF is frequently, caused by a defect in myocardial contraction, and

then the term myocardial failure is appropriate. 3
Epidemiology
• Prevalence:
Affects 5.1 million Americans
Prevalence in developed nations ~ 2%.
Increase with age: affects 6–10% of people over the
age of 65

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Forms of Heart Failure

Low-output Vs High-output Heart Failure

• Low-output HF: occurs secondary to ischemic heart
disease, hypertension, dilated cardiomyopathy, and
valvular and pericardial disease
• High-output HF: occurs in patients with reduced
systemic vascular resistance, i.e., hyperthyroidism,
anemia, pregnancy, arteriovenous fistulas, beriberi,
and Paget’s disease

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Forms of Heart Failure
Acute Versus Chronic Heart Failure
• In acute HF the sudden reduction in cardiac output
often results in systemic hypotension without
peripheral edema.
• Chronic HF is typically observed in patients with
dilated cardiomyopathy or multivalvular heart disease
and develops or progresses slowly.

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 Forms of Heart Failure

Right-sided Vs Left-sided Heart Failure

• Left-sided HF: in patients in whom the left ventricle is
hemodynamically overloaded (e.g., aortic regurgitation) or
weakened due to myocyte loss (e.g., post MI)
 Develop dyspnea and orthopnea as a result of pulmonary
congestion
• Right-sided HF: When the underlying abnormality affects the
right ventricle primarily (e.g., primary pulmonary hypertension
secondary to chronic pulmonary thromboembolism)
 Develop edema, congestive hepatomegaly, and systemic
venous distention
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Forms of Heart Failure

Heart failure with reduced EF (HFrEF)

• Defined as a clinical diagnosis of HF and an LVEF of 40%
or less
• Systolic dysfunction
• Dilated ventricle
• Two thirds of cases are attributable to chronic heart
disease (CHD).
• One third of cases are attributable to nonischemic
cardiomyopathy.

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Forms of Heart Failure
Heart Failure with Preserved EF (HFpEF)
• Diastolic dysfunction
• Defined as an LVEF of 50% or greater; borderline
HFpEF is LVEF 41%–49%
• Impaired ventricular relaxation and filling
• Normal wall motion
• Most common cause is HTN (60%–89%)

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Etiology

• UNDERLYING CAUSES
Ischemic heart disease is responsible for about
three-quarters of all cases.
Cardiomyopathies are second in frequency,
HTN remains an important cause
Congenital and valvular are less common
causes.

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 Etiology….
• Systolic Dysfunction (Decreased Contractility)
Reduction in muscle mass (e.g., myocardial infarction)

Dilated cardiomyopathies

Ventricular hypertrophy

Pressure overload (e.g., systemic or pulmonary

hypertension, aortic or pulmonic valve stenosis)

Volume overload (e.g., valvular regurgitation, shunts, high-

output states)

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 Cont…
• Diastolic Dysfunction (Restriction in Ventricular Filling)
Increased ventricular stiffness
Ventricular hypertrophy (e.g., hypertrophic cardiomyopathy,
pressure and/or volume overload)
Infiltrative myocardial diseases (eg, amyloidosis,
sarcoidosis,
endomyocardial fibrosis)
Myocardial ischemia and infarction
Mitral or tricuspid valve stenosis
Pericardial disease (eg, pericarditis, pericardial tamponade)

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 Cont…
• Non-Ischemic Etiologies
Hypertension
Viral illness
Thyroid disease
Excessive alcohol use
Illicit drug use
Pregnancy-related heart disease
Familial congenital disease
Valvular disorders such as mitral or tricuspid valve
regurgitation or stenosis

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14
 Cont…

Precipitating Causes
1. Infection: The resulting fever, tachycardia, hypoxemia, and
the increased metabolic demands may place a further burden
on an overloaded, but compensated, myocardium of a patient
with chronic heart disease.
2. Arrhythmias:
a) Tachy arrhythmias reduce the time available for
ventricular filling, contributing especially to diastolic HF;
cause ischemic myocardial dysfunction in patients with IHD
b) Slowing of the heart rate associated with complete AV
block or other severe bradyarrhythmias reduces cardiac
output

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 Cont…

Precipitating Causes…
3. Physical, Dietary, Fluid, Environmental, and
Emotional Excesses: The sudden sodium intake as
with a large holiday meal, the inappropriate d/c of drugs
or other therapy for HF, blood transfusions, physical
overexertion, excessive environmental heat or humidity,
and emotional crises all may precipitate HF in patients
who were previously compensated.
4. Myocardial Infarction: a new infarct may further impair
ventricular function and precipitate HF
5. Pulmonary Embolism: Pulmonary emboli may result in
further elevation of pulmonary arterial pressure, which in
turn may produce or intensify ventricular failure 16
 Cont…

Precipitating Causes…
6. Anemia: In the presence of anemia, the oxygen needs of
the metabolizing tissues can be met only by an increase
in the cardiac output
 However, a diseased, overloaded, but otherwise
compensated heart may be unable to augment sufficiently
the volume of blood that it delivers to the periphery.
7. Thyrotoxicosis and Pregnancy: Similar to anemia and
fever, thyrotoxicosis and pregnancy are also high cardiac
output states.
 The development or intensification of HF in a patient with
previously compensated heart disease may actually be one
of the first clinical manifestations of hyperthyroidism
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 Cont…
Precipitating Causes …
8. Aggravation of Hypertension
9. Rheumatic, Viral, and Other Forms of
Myocarditis:
 Acute rheumatic fever and a variety of other
inflammatory or infectious processes affecting the
myocardium may precipitate HF in patients with or
without preexisting heart disease
10.Infective Endocarditis: The additional valvular
damage, anemia, fever, and myocarditis that often
occur as a consequence of infective endocarditis
may, singly or in combination, precipitate HF 18
Cont…
• Drugs Precipitate or Exacerbate Heart Failure
1) Agents Causing Negative Inotropic Effect
Antiarrhythmics (eg, disopyramide, flecainide, and others)
β-blockers (eg, propranolol, metoprolol, atenolol, and
others)
Nondihydropyridine calcium channel blockers (eg,
verapamil)
Itraconazole
Terbinafine

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Cont…
2) Cardiotoxic Agents
 Doxorubicin
 Daunomycin
 Cyclophosphamide
3) Agents Causing Sodium and Water Retention
 Nonsteroidal anti-inflammatory drugs
 COX-2 inhibitors
 Glucocorticoids
 Androgens
 Estrogens
 Salicylates (high dose)
 Sodium-containing drugs (eg, carbenicillin disodium, ticarcillin
disodium)
 Thiazolidinediones (eg, pioglitazone) 20
 PATHOPHYSIOLOGY
Normal Cardiac Function
• CO is defined as the volume of blood ejected per
unit time (L/min) and is the product of heart rate (HR)
and stroke volume (SV):
• CO = HR × SV
• The r/ship between CO and MAP is: MAP = CO ×
systemic vascular resistance (SVR)
• Stroke volume, CO, or both are low in both systolic
and diastolic left ventricular dysfunction, resulting in
decreased tissue perfusion.
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 PATHOPHYSIOLOGY

• Heart failure is a progressive disorder initiated by an

event that impairs the ability of the heart to contract
and/or relax
• The decrease in the heart’s pumping capacity results
in the heart having to rely on compensatory responses
to maintain an adequate cardiac output
• These compensatory responses include
a) Tachycardia and increased contractility through
sympathetic nervous system (SNS) activation
b) An in preload results in an increase in stroke
volume
c) Vasoconstriction and
d) Ventricular hypertrophy and remodeling.
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 PATHOPHYSIOLOGY

a) Increased preload (through Na+ and water

retention)
Renal perfusion in heart failure is reduced
because of depressed cardiac output and
redistribution of blood away from non vital organs.
The kidney interprets the reduced perfusion as an
ineffective blood volume, resulting in activation of
the RAAS in an attempt to maintain blood pressure
and increase renal sodium and water retention.
Optimize stroke volume
Pulmonary and systemic congestion and edema
formation
Increased myocardial oxygen demand 23
 PATHOPHYSIOLOGY

b) Vasoconstriction and increased afterload

• To redistribute blood flow away from nonessential organs to
coronary and cerebral circulations to support blood
pressure, which may be reduced secondary to a decrease
in cardiac output
(mean arterial pressure = CO × SVR)
• A number of neurohormones contribute to the
vasoconstriction including NE, angiotensin II, endothelin-
1, and arginine vasopressin (AVP)
 Maintain BP in face of reduced CO
 Shunt blood from nonessential organs to brain and heart
 Increased myocardial oxygen demand
Increased afterload decreases stroke volume and further24
activates the compensatory responses
 PATHOPHYSIOLOGY

c) Tachycardia and increased contractility (because of

SNS activation)
• The change in heart rate and contractility that rapidly
occurs in response to a drop in cardiac output is
primarily a result of release of norepinephrine (NE) from
adrenergic nerve terminals,
 Helps maintain CO
 Increased myocardial oxygen demand
 Shortened diastolic filling time
 Precipitation of ventricular arrhythmias

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 PATHOPHYSIOLOGY

d) Ventricular hypertrophy and remodeling

• Ventricular hypertrophy is a term used to describe an
increase in ventricular muscle mass.
• Cardiac or ventricular remodeling is a broader term
describing changes in both myocardial cells and
extracellular matrix that result in changes in the size,
shape, structure, and function of the heart
• Angiotensin II, NE, endothelin, aldosterone, vasopressin
and cytokines, that are activated both systemically and
locally in the heart play an important role in initiating the
signal–transduction cascade responsible for ventricular
remodeling

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Clinical Features; Symptoms

• Respiratory:
Exertional dyspnea
Orthopnea
Paroxysmal nocturnal dyspnea
Night cough
• Others:
Fatigue
Edema: from feet upwards
Anorexia and weight loss
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Clinical Features; Signs

• Pulmonary rales, pleural effusion

• Neck vein distension and raised JVP
• Displaced apical impulse
• Gallop rhythm
• Tender hepatomegally
• Cachexia
• Extremity edema

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INVESTIGATIONS
• Diagnostic:
CXR: Useful for detection of cardiac enlargement,
pulmonary edema, and pleural effusions.
 ECG: To assess HR, rhythm, LVH, conduction, previous
MI
Echocardiography: ventricular performance, cardiac
structure.
Other tests:
Blood chemistry: Electrolytes, RFT, FPG, Lipid profile,
CBC: Hgb/HCT, WBC,
U/A

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 Laboratory Tests
 BNP(B-type natriuretic peptide) >100 pg/mL (>29 pmol/L)
 Electrocardiogram may be normal or it could show
numerous abnormalities including acute ST- wave changes
from myocardial ischemia, atrial fibrillation, bradycardia, left
ventricular hypertrophy
 Serum creatinine: it may be increased due to
hypoperfusion.
 Complete blood count useful to determine if heart failure
due to reduced oxygen-carrying capacity.
 Chest x-ray: useful for detection of cardiac enlargement,
pulmonary edema, and pleural effusions
 Hyponatremia: serum sodium <130 mEq/L (<130 mmol/L)

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 DX: Framingham criteria
• Major criteria • Minor criteria
 PND  Extremity edema
 Neck vein distension  Night cough
 +ve HJR  Exertional dyspnea
 Bibasal rales  Hepatomegaly
 Cardiomegally  Pleural effusion
 S3 gallop  Tachycardia(≥100)
 Raised JVP

2 major or 1 major + 2 minor criteria establish clinical DX of

HF

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 Heart Failure Classification
• There are two common systems for categorizing
patients with HF.
1. The New York Heart Association (NYHA) Functional
Classification (FC) system is based on the patient’s
activity level and exercise tolerance.
• It divides patients into one of four classes
• reflects a subjective assessment by a health care provider
and can change frequently over short periods of time.
• Functional class correlates poorly with EF; however, EF is
one of the strongest predictors of prognosis.
• In general, anticipated survival declines in conjunction
with a decline in functional ability. 32
NYHA Functional Classification
Functional Class
I Pts with cardiac disease but without limitation of physical activity.
Ordinary physical activity does not cause undue fatigue, dyspnea, or
palpitation
II Patients with cardiac disease that results in slight limitations of physical
activity. Ordinary physical activity results in fatigue, palpitation,
dyspnea, or angina.

III Patients with cardiac disease that results in marked limitation of

physical activity. Although patients are comfortable at rest, less-than-
ordinary activity will lead to symptoms.

IV Patients with cardiac disease that results in an inability to carry or

physical activity without discomfort. Symptoms of congestive heart
failure are present even at rest. With any physical activity, increased
discomfort is experienced.

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Heart failure classification
2. The American College of Cardiology/American Heart
Association (ACC/AHA)
• based on the development and progression of the disease.
• placed patient into stages A through D

• Draw back: patients can move between NYHA

functional classes as symptoms improve with
treatment, whereas HF staging does not allow for
patients to move to a lower stage (e.g., patients
cannot be categorized as stage C and move to
stage B after treatment

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The American College of Cardiology/American Heart
Association (ACC/AHA)

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 Management
Goals of therapy
Modify or control risk factors (HTN, obesity, DM)
Manage structural heart disease
Reduce morbidity and mortality
Prevent or minimize Na and water retention
Eliminate or minimize HF symptoms
Slow progression of worsening cardiac function

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 TREATMENT OF CHRONIC HEART FAILURE

Desired Therapeutic Outcomes

• There is no cure for HF.

• The general management goals for chronic HF include

 preventing the onset of clinical symptoms or

 reducing symptoms, preventing or reducing hospitalizations,

 slowing progression of the disease

 Improving quality of life, and prolonging survival.

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Treatment algorithm for chronic heart failure.

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Nonpharmacologic Interventions
• Nonpharmacologic treatment involves

dietary modifications such as sodium and fluid

restriction
risk factor reduction including smoking cessation,

 timely immunizations, and

Supervised regular physical activity.

Mechanical, Surgical, and Device Therapies

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 Pharmacologic Therapy: Diuretics
• The primary rationale for the use of diuretic therapy is to
maintain euvolemia in symptomatic or stages C and D heart
failure
• However, do not prolong survival and alter disease progression,
and therefore not considered as mandatory therapy.
• In milder HF, diuretics may be used on an as-needed basis.
• However, once the development of edema is persistent,
regularly scheduled doses will be required.
• Diuretic therapy is usually initiated in low doses in the outpatient
setting, with dosage adjustments based on symptom
assessment and daily body weight.
• diuretics are relatively contraindicated in persons who are
volume depleted or have compromised renal blood flow.
• The concept of ceiling doses for loop diuretics should be
understood. 40
 Diuretics and Recommended Dosing
 Equivalent doses: furosemide 40 mg = bumetanide 1 mg =
torsemide 10–20 mg = ethacrynic acid 50 mg

Oral BA Initial Maximal Daily Duration of

Agent
(%) Daily Dose Dose (mg) Action (hr)

Loop Diuretics (inhibit 20%–25% of sodium reabsorption)

20–40 mg
Furosemide 10–67 daily 600 6–8
or BID
0.5–1 mg
Bumetanide 80–100 daily 10 4–6
or BID
10–20 mg
Torsemide 80–100 200 12–16
daily
25–50 mg
Ethacrynic acid 100 daily 200 6–8
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or BID
 ACEIs
 Cornerstone of pharmacotherapy for patients with SHF
 Deleterious effects of angiotensin II and aldosterone blocked
 Improve survival by 20% to 30% compared with placebo.
 Prevent the development of HF and reduce cardiovascular risk
 ACE inhibitors improve symptoms, slow disease progression,
and decrease mortality in patients with HF and reduced LVEF
(Stage C) is unequivocal
 The benefits of ACE inhibitor therapy are independent of the
etiology of HF (ischemic vs. non-ischemic) and are observed in
patients with mild, moderate, or severe symptoms.
 ACE inhibitors administered after MI improve overall survival,
decrease development of severe HF, and reduce reinfarction
and HF hospitalization rates.
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 ACEIs
 ACE inhibitors should be prescribed to all patients with HF due
to left ventricular systolic dysfunction (LVEF) unless they have
a contradiction to their use or have been shown to be unable
to tolerate treatment with these drugs
 ACE inhibitors should be initiated using low doses and titrated
up to target doses over several weeks depending on
tolerability (adverse effects and blood pressure)
 Higher doses of ACEI may reduce the risk of hospitalization,
but not mortality, compared with lower doses.
 However, clinicians should attempt to use ACE inhibitor doses
proven beneficial in clinical trials.

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Dosing and Monitoring for Neurohormonal Blocking
Agents

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 Hydralazine and Isosorbide Dinitrate
• Complementary hemodynamic actions originally led to the
combination of nitrates with hydralazine.
Nitrates reduce preload by causing primarily venous vasodilation
through activating guanylate cyclase and a subsequent increase
in cyclic guanosine monophosphate (cGMP) in vascular smooth
muscle.
Hydralazine reduces afterload through direct arterial smooth
muscle relaxation via an unknown mechanism.
• The beneficial effect of an external nitric oxide source may be
more apparent in the African-American population, which
appears to be predisposed to having an imbalance in nitric oxide
production
• In addition, hydralazine may reduce the development of nitrate
tolerance when nitrates are given chronically
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 Beta-Adrenergic Antagonists
• They reduce morbidity and mortality in patients with SHF__
carvedilol, metoprolol succinate (CR/XL), and bisoprolol.
• should be used in all stable patients with HF and a reduced
left ventricular EF in the absence of contraindications or a clear
history of β-blocker intolerance
• Patients should receive a β-blocker even if their symptoms are
mild or well controlled with diuretic and ACE inhibitor therapy.
• Importantly, it is not essential that ACE inhibitor doses be
optimized before a β-blocker is started because the addition of
a β-blocker is likely to be of greater benefit than an increase in
ACE inhibitor dose.
• β-blocker therapy is expected to positively influence disease
progression and survival even if there is little to no
symptomatic improvement.
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 Beta-Adrenergic Antagonists
 In addition to improving survival, β-blockers have been shown to
improve:
all-cause hospitalization
reductions in hospitalizations for worsening HF
increases in LVEF of 5 to 10 units
• β-Blockers have also been shown to decrease ventricular mass,
improve the sphericity of the ventricle, and reduce systolic and
diastolic volumes (left ventricular end-systolic volume and
LVEDV)___ Reverse remodelling.
• In the absence of more compelling evidence, ACE inhibitors
should be started first in most patients.

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 Beta-Adrenergic Antagonists
 Initiating a β-blocker first may be advantageous for patients with:
evidence of excessive SNS activity (e.g., tachycardia) and
renal function or potassium concentrations preclude starting
an ACE inhibitor (or ARB) at that time.
Anti-arrhythmic effects, attenuating or reversing ventricular
remodeling.
• β-Blockers should be initiated in stable patients who have no or
minimal evidence of fluid overload.
• To minimize the likelihood for acute decompensation, β-blockers
should be started in very low doses with slow upward dose
titration.
• β-Blocker doses should be doubled no more often than every 2
weeks

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 Beta-Adrenergic Antagonists
• In patients with HFpEF, β-blockers may help to lower and
maintain low pulmonary venous pressures by decreasing HR
and increasing the duration of diastole
• Tachycardia is poorly tolerated in patients with HFpEF for
several reasons.
rapid HRs cause an increase in myocardial oxygen demand
and a decrease in coronary perfusion time.
incomplete relaxation between cardiac cycles may result in
an increase in diastolic pressure relative to volume.
rapid rate reduces diastolic filling time and ventricular filling

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Dosing and Monitoring for Neurohormonal Blocking Agents

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 Aldosterone Antagonists
• Currently, the aldosterone antagonists available are spironolactone
and eplerenone.

• Both agents are inhibitors of aldosterone that produce weak

diuretic effects while sparing potassium concentrations.

• Eplerenone is selective for the mineralocorticoid receptor and

hence does not exhibit the endocrine adverse-effect profile
commonly seen with spironolactone.

• The initial rationale for specifically targeting aldosterone for

treatment of HF was based on the knowledge that ACE inhibitors
do not suppress the chronic production and release of aldosterone.
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 Aldosterone Antagonists
• The major risk related to aldosterone antagonists is
• hyperkalemia

• Renal failure

• Gynecomastia ( spironolactone)

• Eplerenone is a CYP3A4 substrate and should not be

used concomitantly with strong inhibitors of 3A4

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 Digoxin
• Digoxin exerts positive inotropic effects through binding to
sodium- and potassium activated adenosine triphosphatase
(ATP) pumps, leading to increased intracellular sodium
concentrations and subsequently more available intracellular
calcium during systole.
• Neurohormonal effects( restore baroreceptor sensitivity)
• Digoxin was shown to decrease HF-related hospitalizations but
did not decrease HF progression or improve survival

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Clinical Pharmacokinetics of Digoxin

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 Other medication therapies
• Anticoagulation
Recommended for HF with permanent, persistent, or
paroxysmal AF
Not recommended in the absence of AF, prior stroke, or a
cardioembolic source
• Antiarrhythmics:
Given the neutral effects on mortality, the preferred
antiarrhythmics in patients with HFrEF are dofetilide
(AF/atrial flutter) and amiodarone.

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 Reference
1. Dipiro JT, Talbert RL, Yee GC, et.al. Pharmacotherapy, A
Pathophysiologic Approach. 12th edition.
2. Koda - Kimble MA, Young LY , Kradjan WA, et.al. Applied Therapeutics,
The Clinical Use of Drugs. 11th edition.

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