A Guide to the Etiology,

Pathophysiology, Diagnosis,
and Treatment of Heart Failure
Howard Weinberg, D.O., F.A.C.C.
South Jersey Heart Group
September 2007
Created in association with
Dr. Philip B. Adamson, Director
Congestive Heart Failure Treatment Program
Objectives:

Upon completing the session, the participant will be

able to:
• Describe the incidence and prevalence of heart failure
• List the common etiologies of heart failure
• Define the compensatory mechanisms that occur due to
heart failure
• Identify current assessment and treatment modalities for
heart failure patients
 Part I:
Etiology and Pathophysiology of
Heart Failure
Heart Failure (HF) Definition

A complex clinical syndrome in which the heart is

incapable of maintaining a cardiac output adequate
to accommodate metabolic requirements and the
venous return.
 HF Incidence and Prevalence
• Prevalence
– Worldwide, 22 million1
– United States, 5 million2
• Incidence
– Worldwide, 2 million new cases annually1
– United States, 500,000 new cases annually2
• HF afflicts 10 out of every 1,000 over age 65 in
the U.S.2

1 World Health Statistics, World Health Organization, 1995.

2 American Heart Association, 2002 Heart and Stroke Statistical Update.
 Prevalence of HF by Age and Gender

United States: 1988-94

10
Males
8
Females

Percent of 6
Population
4

0
20-24 25-34 35-44 45-54 55-64 65-74 75+

Source: NHANES III (1988-94), CDC/NCHS and the American Heart Association
New York Heart Association
Functional Classification

Class I: No symptoms with ordinary activity

Class II: Slight limitation of physical activity. Comfortable at rest,
but ordinary physical activity results in fatigue,
palpitation, dyspnea, or angina
Class III: Marked limitation of physical activity. Comfortable at
rest, but less than ordinary physical activity results in
fatigue, palpitation, dyspnea, or anginal pain
Class IV: Unable to carry out any physical activity without
discomfort. Symptoms of cardiac insufficiency may be
present even at rest
HF Classification: Evolution and
Disease Progression
• Four Stages of HF (ACC/AHA Guidelines):
Stage A: Patient at high risk for developing HF with no
structural disorder of the heart
Stage B: Patient with structural disorder without symptoms
of HF
Stage C: Patient with past or current symptoms of HF
associated with underlying structural heart disease
Stage D: Patient with end-stage disease who requires
specialized treatment strategies

Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of

Chronic Heart Failure in the Adult, 2001
 Severity of Heart Failure
Modes of Death

NYHA II CHF NYHA III

CHF
12% Other
26%
Other
24% Sudden 59%
Death Sudden
64% n = 103 15% Death
n = 103
NYHA IV
CHF

33% Other
56%
Sudden
Death
11%
n = 27

MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized
intervention trial in congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07.
Etiology of Heart Failure

What causes heart failure?

• The loss of a critical quantity of functioning
myocardial cells after injury to the heart due to:
– Ischemic Heart Disease
– Hypertension
– Idiopathic Cardiomyopathy
– Infections (e.g., viral myocarditis, Chagas’ disease)
– Toxins (e.g., alcohol or cytotoxic drugs)
– Valvular Disease
– Prolonged Arrhythmias
The Donkey Analogy
Ventricular dysfunction limits a patient's ability to perform the
routine activities of daily living…
Left Ventricular Dysfunction
• Systolic: Impaired contractility/ejection
– Approximately two-thirds of heart failure patients have systolic
dysfunction1
• Diastolic: Impaired filling/relaxation

30%
(EF > 40 %)
(EF < 40%)

70%

Diastolic Dysfunction
Systolic Dysfunction
1 Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200
Cardiac Output
• Cardiac output is the amount of blood that the
ventricle ejects per minute

Cardiac Output = HR x SV
Determinants of Ventricular Function

Contractility

Preload Afterload
Stroke
Volume
• Synergistic LV Contraction
• Wall Integrity
• Valvular Competence
Heart Rate

Cardiac Output
Left Ventricular Dysfunction
Volume Pressure Loss of Impaired
Overload Overload Myocardium Contractility

LV Dysfunction
EF < 40%

 End Systolic Volume

 Cardiac
Output
 End Diastolic Volume

Hypoperfusion Pulmonary Congestion

Hemodynamic Basis for
Heart Failure Symptoms
Hemodynamic Basis for
Heart Failure Symptoms

LVEDP 

Left Atrial Pressure 

Pulmonary Capillary Pressure 

Pulmonary Congestion
Left Ventricular Dysfunction
Systolic and Diastolic
• Symptoms • Physical Signs
– Dyspnea on Exertion – Basilar Rales
– Paroxysmal Nocturnal – Pulmonary Edema
Dyspnea
– S3 Gallop
– Tachycardia
– Pleural Effusion
– Cough
– Cheyne-Stokes Respiration
– Hemoptysis
Right Ventricular Failure
Systolic and Diastolic
• Symptoms • Physical Signs
– Abdominal Pain – Peripheral Edema
– Anorexia – Jugular Venous Distention
– Nausea – Abdominal-Jugular Reflux
– Bloating – Hepatomegaly
– Swelling
Consequences of Decreased
Mean Arterial Pressure

 Mean Arterial Pressure (BP)

=
 Cardiac Output
x
Total Peripheral Resistance
Compensatory Mechanisms

• Frank-Starling Mechanism

• Neurohormonal Activation

• Ventricular Remodeling
Compensatory Mechanisms

Frank-Starling Mechanism
a. At rest, no HF
b. HF due to LV systolic dysfunction
c. Advanced HF
Compensatory Mechanisms

Neurohormonal Activation
Many different hormone systems are involved in
maintaining normal cardiovascular homeostasis,
including:
• Sympathetic nervous system (SNS)
• Renin-angiotensin-aldosterone system (RAAS)
• Vasopressin (a.k.a. antidiuretic hormone, ADH)
Compensatory Mechanisms:
Sympathetic Nervous System

Decreased MAP

Sympathetic Nervous System

 Contractility Tachycardia Vasoconstriction

MAP = (SV x HR) x TPR

 Sympathetic Activation in Heart Failure
 CNS sympathetic outflow

 Cardiac sympathetic  Sympathetic

activity activity to kidneys
+ peripheral vasculature

1- 2- 1- Activation

1- b1-
receptors receptors receptors of RAS

Myocardial toxicity Vasoconstriction

Increased arrhythmias Sodium retention

Disease progression
Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.
Compensatory Mechanisms:
Renin-Angiotensin-Aldosterone (RAAS)
Angiotensinogen
Renin
Angiotensin I
Angiotensin
Converting
Enzyme Angiotensin II

AT I receptor

Vasoconstriction Vascular remodeling

Oxidative Stress LV remodeling

Cell Growth Proteinuria

Compensatory Mechanisms:
Renin-Angiotensin-Aldosterone (RAAS)

Renin-Angiotensin-Aldosterone
( renal perfusion)

Salt-water retention Sympathetic

Vasoconstriction
Thirst augmentation

MAP = (SV x HR) x TPR

Compensatory Mechanisms:
Neurohormonal Activation – Vasopressin

Decreased systemic blood pressure

Central baroreceptors
-

Increased systemic blood pressure Stimulation of hypothalamus, which produces

vasopressin for release by pituitary gland

Vasoconstriction Release of vasopressin by pituitary gland

Compensatory Neurohormonal Stimulation:
Summary
Decreased Cardiac Output

Sympathetic Renin-angiotensin Antidiuretic hormone

nervous system system (vasopressin)

Contractility Heart Vasoconstriction Circulating volume

rate
Anteriolar Venous

Maintain
blood
pressure Venous return
to heart
( preload)
Cardiac
+ output - Peripheral edema
and pulmonary
+ congestion
Stroke
volume
Compensatory Mechanisms
Ventricular Remodeling
Alterations in the heart’s size, shape, structure, and function brought about
by the chronic hemodynamic stresses experienced by the failing heart.

Curry CW, et al. Mechanical dyssynchrony in dilated cardiomyopathy with intraventricular conduction
delay as depicted by 3D tagged magnetic resonance imaging. Circulation 2000 Jan 4;101(1):E2.
Other Neurohormones
• Natriuretic Peptides: Three known types
– Atrial Natriuretic Peptide (ANP)
• Predominantly found in the atria
• Diuretic and vasodilatory properties
– Brain Natriuretic Peptide (hBNP)
• Predominantly found in the cardiac ventricles
• Diuretic and vasodilatory properties
– C-type Natriuretic Peptide (CNP)
• Predominantly found in the central nervous system
• Limited natriuretic and vasodilatory properties
Pharmacological Actions of hBNP

Hemodynamic
(balanced vasodilation)
• veins
M
D
R I SS
S
S
• arteries
K G
R
G
F
C
L
G
R
H • coronary arteries
C S S R

Neurohormonal
K V L
G
S P K M V
Q G S

aldosterone
norepinephrine
Renal
diuresis & natriuresis

Abraham WT and Schrier RW, 1994

Endothelium-Derived Vasoactive Substances

Produced by a thin lining of cells within the arteries and veins

called the endothelium
Endothelium-derived relaxing factors (EDRF) – Vasodilators:
• Nitric Oxide (NO)
• Bradykinin
• Prostacyclin
Endothelium-derived constricting factors (EDCF) –
Vasoconstrictors:
• Endothelin I
Mediators of Heart Failure

Cytokines
• Small protein molecules produced by a variety of
tissues and cells
• Negative inotropes
• Elevated levels associated with worse clinical
outcomes
• Examples:
– Tumor necrosis factor (TNF)-alpha
– Interleukin 1-alpha
– Interleukin-2
– Interleukin-6
– Interferon-alpha
Vicious Cycle of Heart Failure

LV Dysfunction

Decreased cardiac output

Increased cardiac workload and
(increased preload and afterload) Decreased blood pressure

Increased cardiac output (via increased Frank-Starling Mechanism

contractility and heart rate) Remodeling
Increased blood pressure (via vasoconstriction Neurohormonal activation
and increased blood volume)
 Neurohormonal Responses to Impaired
Cardiac Performance
Initially Adaptive, Deleterious if Sustained
Short-Term Effects Long-Term Effects
Response

Salt and Water Retention Augments Preload Pulmonary Congestion,

Anasarca

Vasoconstriction Maintains BP for perfusion Exacerbates pump

of vital organs dysfunction (excessive
afterload), increases
cardiac energy
expenditure

Sympathetic Stimulation Increases HR and ejection Increases energy

expenditure

Jaski, B, MD: Basics of Heart Failure: A Problem Solving Approach

 Part II:
Assessing Heart Failure
Assessing Heart Failure
• Patient History
• Physical Examination
• Laboratory and Diagnostic Tests
Kriteria Major Kriteria Minor
• Paroksimal • Edema ekstremitas
noktunal dispnea • Batuk malam hari
• Distensi vena leher • Dispnea d’effort
• Ronki paru • Hepatomegali
• Kardiomegali • Efusi pleura
• Edema paru akut • Penurunan
• Gallop S3 kapasitas vital 1/3
• Peninggian tekanan dari normal
vena jugularis • Takikardia
• Refluks (>120/menit.
hepatojugular
Diagnostic Evaluation of
New Onset Heart Failure
• Determine the type of cardiac dysfunction
(systolic vs. diastolic)
• Determine Etiology
• Define prognosis
• Guide therapy
Diagnostic Evaluation of
New Onset Heart Failure

Initial Work-up:
• ECG
• Chest x-ray
• Blood work
• Echocardiography
 Part III:
Current Treatment
of Heart Failure
General Measures

Lifestyle Modifications: Medical Considerations:

• Weight reduction • Treat HTN, hyperlipidemia,
diabetes, arrhythmias
• Discontinue smoking
• Coronary revascularization
• Avoid alcohol and other • Anticoagulation
cardiotoxic substances
• Immunization
• Exercise
• Sodium restriction
• Daily weights
• Close outpatient monitoring
Pharmacologic Management
Digoxin
• Enhances inotropy of cardiac muscle
• Reduces activation of SNS and RAAS
• Controlled trials have shown long-term digoxin therapy:
– Reduces symptoms
– Increases exercise tolerance
– Improves hemodynamics
– Decreases risk of HF progression
– Reduces hospitalization rates for decompensated HF
– Does not improve survival
Digitalis Compounds

Like the carrot placed in front of the donkey

Pharmacologic Management

Diuretics
• Used to relieve fluid retention
• Improve exercise tolerance
• Facilitate the use of other drugs indicated for heart failure
• Patients can be taught to adjust their diuretic dose based
on changes in body weight
• Electrolyte depletion a frequent complication
• Should never be used alone to treat heart failure
• Higher doses of diuretics are associated with increased
mortality
Pharmacologic Management

ACE Inhibitors
• Blocks the conversion of angiotensin I to angiotensin II;
prevents functional deterioration
• Recommended for all heart failure patients
• Relieves symptoms and improves exercise tolerance
• Reduces risk of death and decreases disease
progression
• Benefits may not be apparent for 1-2 months after
initiation
Diuretics, ACE Inhibitors

Reduce the number of sacks on the wagon

Pharmacologic Management

Beta-Blockers
• Cardioprotective effects due to blockade of excessive
SNS stimulation
• In the short-term, beta blocker decreases myocardial
contractility; increase in EF after 1-3 months of use
• Long-term, placebo-controlled trials have shown
symptomatic improvement in patients treated with
certain beta-blockers1
• When combined with conventional HF therapy, beta-
blockers reduce the combined risk of morbidity and
mortality, or disease progression1

1 Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management

of Chronic Heart Failure in the Adult, 2001 p. 20.
ß-Blockers

Limit the donkey’s speed, thus saving energy

Pharmacologic Management

Aldosterone Antagonists
• Generally well-tolerated
• Shown to reduce heart failure-related morbidity and
mortality
• Generally reserved for patients with NYHA Class III-IV HF
• Side effects include hyperkalemia and gynecomastia.
Potassium and creatinine levels should be closely
monitored
Pharmacologic Management

Angiotensin Receptor Blockers (ARBs)

• Block AT1 receptors, which bind circulating angiotensin II
• Examples: valsartan, candesartan, losartan
• Should not be considered equivalent or superior to ACE
inhibitors
• In clinical practice, ARBs should be used to treat patients
who are ACE intolerant due to intractable cough or who
develop angioedema
Angiotensin II Receptors

AT1 receptor AT2 receptor

• Vasoconstriction • Vasodilation
• Growth Promotion • Growth inhibition
• Anti-apoptotic • Pro-apoptotic
• Pro-fibrotic • ? Fibrosis
• Pro-thrombotic • ? Thrombosis
• Pro-oxidant • ? redox
 Part IV:
Assessment and Treatment of
the Heart Failure Patient
Treatment Approach for the Patient
with Heart Failure
Stage A Stage B Stage C Stage D
At high risk, no Structural heart Structural heart Refractory HF
structural disease disease, disease with requiring
asymptomatic prior/current specialized
symptoms of HF interventions

Therapy Therapy Therapy Therapy

• Treat Hypertension • All measures • All measures • All measures
• Treat lipid under stage A under stage A under stages A,B,
disorders • ACE inhibitors in Drugs: and C

• Encourage regular appropriate • Diuretics • Mechanical assist

patients devices
exercise • ACE inhibitors
• Discourage alcohol • Beta-blockers in • Heart
appropriate • Beta-blockers transplantation
intake
patients • Digitalis • Continuous (not
• ACE inhibition
• Dietary salt intermittent) IV
restriction inotropic infusions
for palliation
• Hospice care

Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of

Chronic Heart Failure in the Adult, 2001
Cardiac Resynchronization Therapy

Increase the donkey’s (heart) efficiency

Summary
• Heart failure is a chronic, progressive disease that is
generally not curable, but treatable
• Most recent guidelines promote lifestyle modifications and
medical management with ACE inhibitors, beta blockers,
digoxin, and diuretics
• It is estimated 15% of all heart failure patients may be
candidates for cardiac resynchronization therapy (see later
section for details)
• Close follow-up of the heart failure patient is essential, with
necessary adjustments in medical management