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
6
Percent of
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 Heart Rate
Valvular Competence

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- 1-
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 hearts 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
K
D
R I SS
S
S
arteries
G

coronary arteries
R L
G G H
F R
C R
C S S K V L
S P K M V
Q G S
G
Neurohormonal
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 deffort
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.
-Blockers

Limit the donkeys 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 under All measures under All measures under
stage A stage A stages A,B, and C
Treat lipid
disorders ACE inhibitors in Drugs: Mechanical assist
appropriate devices
Encourage regular Diuretics
patients
exercise Heart
ACE inhibitors
Beta-blockers in transplantation
Discourage alcohol
appropriate Beta-blockers
intake Continuous (not
patients
Digitalis intermittent) IV
ACE inhibition
inotropic infusions
Dietary salt
for palliation
restriction
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 donkeys (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