Heart Failure

Pathogenesis Diagnosis and

Management
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
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
Enlarged heart
Systolic dysfunction
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

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
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
• arteries
R I SS
D S
M
S
K G

• coronary arteries
R L
G H
G
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
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 Long-Term Effects
Response Effects

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

Assessing Heart Failure

• Patient History

• Physical Examination

• Laboratory and Diagnostic Tests

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
Diagnostic Evaluation of
New Onset Heart Failure

LV
RV

Septum

LV cavity

LA
LV Wall
RA

M-Mode Echo 2D Echo

The Vicious Cycle of
Heart Failure Management

Chronic HF
SOB
Diurese &
Home  Weight

Hospitalization MD’s Office

IV Lasix
or Admit PO Lasix

Emergency
Room
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-blockers 1
• 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
Proven Outcomes for HF Therapies
• Improve Survival
– ACE inhibitor • Reduce Hospitalization
– ARB – ACE inhibitor

– Beta blocker – ARB

– Aldosterone receptor – Beta blocker

antagonist – Aldosterone receptor
– Hydralazine/long-acting antagonist
nitrates – Hydralazine/long-acting
nitrates
– Digoxin
Cardiac Resynchronization Therapy

Increase the donkey’s (heart) efficiency

Cardiac Resynchronization Therapy

Patient Indications
CRT device:
– Moderate to severe HF (NYHA Class III/IV) patients
– Symptomatic despite optimal, medical therapy
– QRS  130 msec
– LVEF  35%

CRT plus ICD:

– Same as above with ICD indication
 Cardiac Resynchronization Therapy:
Creating Realistic Patient Expectations

• Approximately two-third of patients should

experience improvement (responders vs.
non-responders)1
– Some patients may not experience immediate
improvement

Note: CRT is adjunctive and is not intended to replace medical therapy.

Patients will continue to be followed by HF Specialist and Physician
managing implantable devices.

1 Abraham, WT, et. Al. Cardiac Resynchronization in Chronic Heart Failure. N Engl J Med 2002;346:1845-53
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