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 8 Percent of Population 6 4 2 0 20-24 25-34 35-44 45-54 55-64 65-74 75+ Males Females

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

New York Heart Association Functional Classification

Class I: Class II: No symptoms with ordinary activity Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, dyspnea, or angina Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency may be present even at rest

Class III:

Class IV:

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
12% CHF Other Sudden Death
n = 103

NYHA III
CHF 26% Other Sudden Death
n = 103

24%
64%

59%
15%

NYHA IV CHF 33% 56% 11% Sudden Death

n = 27

Other

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 Overload Pressure Overload Loss of Myocardium Impaired 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
Dyspnea on Exertion

Physical Signs
Basilar Rales

Paroxysmal Nocturnal Dyspnea

Tachycardia

Pulmonary Edema
S3 Gallop Pleural Effusion

Cough
Hemoptysis

Cheyne-Stokes Respiration

Right Ventricular Failure Systolic and Diastolic

Symptoms
Abdominal Pain

Physical Signs
Peripheral Edema

Anorexia
Nausea Bloating

Jugular Venous Distention

Abdominal-Jugular Reflux 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 activity
1receptors 2receptors 1receptors

Sympathetic activity to kidneys + peripheral vasculature

11Activation of RAS

Myocardial toxicity Increased arrhythmias

Vasoconstriction 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 Oxidative Stress Vascular remodeling LV remodeling

Cell Growth

Proteinuria

Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS)

Renin-Angiotensin-Aldosterone ( renal perfusion)

Salt-water retention Thirst
Sympathetic augmentation

Vasoconstriction

MAP = (SV x HR) x TPR

Compensatory Mechanisms: Neurohormonal Activation Vasopressin

Decreased systemic blood pressure

Central baroreceptors Stimulation of hypothalamus, which produces vasopressin for release by pituitary gland

Increased systemic blood pressure

Vasoconstriction

Release of vasopressin by pituitary gland

Compensatory Neurohormonal Stimulation: Summary

Decreased Cardiac Output Sympathetic nervous system Renin-angiotensin system Antidiuretic hormone (vasopressin)

Contractility

Heart rate

Vasoconstriction

Circulating volume

Anteriolar
Maintain blood pressure

Venous

Venous return to heart ( preload)

Cardiac output

+
Stroke volume

Peripheral edema and pulmonary congestion

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)
D M K R G F S P K M V Q G S C S S G R I SS S S G L H G R C R K V L

veins arteries coronary arteries 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

Increased cardiac workload (increased preload and afterload)

Decreased cardiac output and Decreased blood pressure

Increased cardiac output (via increased contractility and heart rate) Increased blood pressure (via vasoconstriction and increased blood volume)

Frank-Starling Mechanism Remodeling Neurohormonal activation

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 Increases HR and ejection Increases energy expenditure

Sympathetic Stimulation

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 Paroksimal noktunal dispnea Distensi vena leher Ronki paru Kardiomegali Edema paru akut Gallop S3 Peninggian tekanan vena jugularis Refluks hepatojugular

Kriteria Minor Edema ekstremitas Batuk malam hari Dispnea deffort Hepatomegali Efusi pleura Penurunan kapasitas vital 1/3 dari normal Takikardia (>120/menit.

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: Weight reduction Medical Considerations: Treat HTN, hyperlipidemia, diabetes, arrhythmias

Discontinue smoking
Avoid alcohol and other cardiotoxic substances

Coronary revascularization
Anticoagulation Immunization Sodium restriction Daily weights Close outpatient monitoring

Exercise

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, betablockers 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
Vasoconstriction

AT2 receptor
Vasodilation

Growth Promotion
Anti-apoptotic Pro-fibrotic

Growth inhibition
Pro-apoptotic ? Fibrosis

Pro-thrombotic
Pro-oxidant

? Thrombosis
? 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 disease

Structural heart disease, asymptomatic

Structural heart disease with prior/current symptoms of HF

Therapy All measures under stage A Drugs: Diuretics ACE inhibitors Beta-blockers Digitalis Dietary salt restriction

Refractory HF requiring specialized interventions

Therapy All measures under stages A,B, and C Mechanical assist devices Heart transplantation Continuous (not intermittent) IV inotropic infusions for palliation Hospice care

Therapy Treat Hypertension Treat lipid disorders Encourage regular exercise Discourage alcohol intake ACE inhibition

Therapy All measures under stage A ACE inhibitors in appropriate patients Beta-blockers in appropriate patients

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