A Guide to the Etiology, Pathophysiology, Diagnosis, and Treatment of Heart Failure

1
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

2

• This presentation is provided for educational
  purposes only and should not be considered the
  only source for this type of information. At all
  times, it is the professional decision of the
  practitioner to exercise independent judgment in
  a particular situation.

3
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

4
Part I Etiology and Pathophysiology of Heart
Failure
5
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.

6
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.
7
Prevalence of HF by Age and Gender

• United States 1988-94

Source NHANES III (1988-94), CDC/NCHS and the
American Heart Association
8
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

9
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
10
Severity of Heart FailureModes of Death
NYHA II
NYHA III
CHF
CHF
12
Other
26
Other
59
Sudden
24
Sudden
Death
64
15
Death
n 103
n 103
NYHA IV
CHF
Other
33
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. 19993532001-07.
11
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

12
The Donkey Analogy

• Ventricular dysfunction limits a patient's
  ability to perform the routine activities of
  daily living

13
Left Ventricular Dysfunction

• Systolic Impaired contractility/ejection
• Approximately two-thirds of heart failure
  patients have systolic dysfunction1
• Diastolic Impaired filling/relaxation

30
(EF gt 40 )
(EF lt 40)
70
Diastolic Dysfunction
Systolic Dysfunction
1 Lilly, L. Pathophysiology of Heart Disease.
Second Edition p 200
14
Cardiac Output

• Cardiac output is the amount of blood that the
  ventricle ejects per minute

Cardiac Output HR x SV
15
Determinants of Ventricular Function
Contractility
Preload
Afterload
Stroke Volume

• Synergistic LV Contraction
• Wall Integrity
• Valvular Competence

Heart Rate
Cardiac Output
16
Left Ventricular Dysfunction
Volume Overload
Pressure Overload
Loss of Myocardium
Impaired Contractility
LV Dysfunction EF lt 40
? End Systolic Volume
? Cardiac Output
? End Diastolic Volume
Hypoperfusion
Pulmonary Congestion
17
Hemodynamic Basis for Heart Failure Symptoms
18
Hemodynamic Basis forHeart Failure Symptoms

• LVEDP ?
• Left Atrial Pressure ?
• Pulmonary Capillary Pressure ?
• Pulmonary Congestion

19
Left Ventricular DysfunctionSystolic and
Diastolic

• Symptoms
• Dyspnea on Exertion
• Paroxysmal Nocturnal Dyspnea
• Tachycardia
• Cough
• Hemoptysis

• Physical Signs
• Basilar Rales
• Pulmonary Edema
• S3 Gallop
• Pleural Effusion
• Cheyne-Stokes Respiration

20
Right Ventricular FailureSystolic and Diastolic

• Symptoms
• Abdominal Pain
• Anorexia
• Nausea
• Bloating
• Swelling

• Physical Signs
• Peripheral Edema
• Jugular Venous Distention
• Abdominal-Jugular Reflux
• Hepatomegaly

21
Consequences of DecreasedMean Arterial Pressure

• ? Mean Arterial Pressure (BP)
• ? Cardiac Output
• x
• Total Peripheral Resistance

22
Compensatory Mechanisms

• Frank-Starling Mechanism
• Neurohormonal Activation
• Ventricular Remodeling

23
Compensatory Mechanisms

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

24
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)

25
Compensatory Mechanisms Sympathetic Nervous
System
Decreased MAP
Sympathetic Nervous System
? Contractility
Tachycardia
Vasoconstriction
?MAP (?SV x ?HR) x ?TPR
26
Sympathetic Activation in Heart Failure
? CNS sympathetic outflow
Disease progression
Packer. Progr Cardiovasc Dis. 199839(suppl
I)39-52.
27
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
28
Compensatory Mechanisms
Renin-Angiotensin-Aldosterone (RAAS)
Renin-Angiotensin-Aldosterone (? renal perfusion)
Salt-water retention Thirst
Sympathetic augmentation
Vasoconstriction
?MAP (?SV x ?HR) x ?TPR
29
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
Release of vasopressin by pituitary gland
Vasoconstriction
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Compensatory Neurohormonal Stimulation Summary
Decreased Cardiac Output
Sympatheticnervous system
Renin-angiotensinsystem
Antidiuretic hormone(vasopressin)
Contractility
Vasoconstriction
Circulating volume
Heartrate
Anteriolar
Venous
Maintainbloodpressure
Venous return to heart( preload)
Cardiacoutput
-

Peripheral edemaand pulmonarycongestion

Strokevolume
31
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
4101(1)E2.
32
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

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Pharmacological Actions of hBNP
Hemodynamic (balanced vasodilation) veins
arteries coronary arteries Neurohormonal al
dosterone norepinephrine Renal diuresis
natriuresis


Abraham WT and Schrier RW, 1994
34
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

35
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

36
Vicious Cycle of Heart Failure
LV Dysfunction
Decreased cardiac output and Decreased blood
pressure
Increased cardiac workload (increased preload and
afterload)
Frank-Starling Mechanism Remodeling Neurohormonal
activation
Increased cardiac output (via increased contractil
ity and heart rate) Increased blood pressure (via
vasoconstriction and increased blood volume)
37
Neurohormonal Responses to ImpairedCardiac
Performance
Initially Adaptive, Deleterious if Sustained
Jaski, B, MD Basics of Heart Failure A
Problem Solving Approach
38
Part IIAssessing Heart Failure
39
Assessing Heart Failure

• Patient History
• Physical Examination
• Laboratory and Diagnostic Tests

40
Diagnostic Evaluation of New Onset Heart Failure

• Determine the type of cardiac dysfunction
  (systolic vs. diastolic)
• Determine Etiology
• Define prognosis
• Guide therapy

41
Diagnostic Evaluation of New Onset Heart Failure

• Initial Work-up
• ECG
• Chest x-ray
• Blood work
• Echocardiography

42
Diagnostic Evaluation of New Onset Heart Failure
LV
RV
Septum
LV cavity
LA
LV Wall
RA
2D Echo
M-Mode Echo
43
Part III Current Treatment of Heart Failure
44
The Vicious Cycle of Heart Failure Management
Chronic HF
SOB ? Weight
Diurese Home
Hospitalization
MDs Office
IV Lasix or Admit
PO Lasix
Emergency Room
45
General Measures

• Lifestyle Modifications
• Weight reduction
• Discontinue smoking
• Avoid alcohol and other cardiotoxic substances
• Exercise

• Medical Considerations
• Treat HTN, hyperlipidemia, diabetes, arrhythmias
• Coronary revascularization
• Anticoagulation
• Immunization
• Sodium restriction
• Daily weights
• Close outpatient monitoring

46
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

47
Digitalis Compounds

• Like the carrot placed in front of the donkey

48
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

49
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

50
Diuretics, ACE Inhibitors

• Reduce the number of sacks on the wagon

51
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.
52
ß-Blockers

• Limit the donkeys speed, thus saving energy

53
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

54
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

55
Angiotensin II Receptors
AT1 receptor
AT2 receptor

• Vasoconstriction
• Growth Promotion
• Anti-apoptotic
• Pro-fibrotic
• Pro-thrombotic
• Pro-oxidant

• Vasodilation
• Growth inhibition
• Pro-apoptotic
• ? Fibrosis
• ? Thrombosis
• ? redox

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Part IVAssessment and Treatment of the Heart
Failure Patient
57
Treatment Approach for the Patient with Heart
Failure
Stage A At high risk, no structural disease
Stage B Structural heart disease, asymptomatic
Stage D Refractory HF requiring specialized
interventions
Stage C Structural heart disease with
prior/current symptoms of HF

• 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

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

• Therapy
• All measures under stages A,B, and C
• Mechanical assist devices
• Heart transplantation
• Continuous (not intermittent) IV 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
58
Cardiac Resynchronization Therapy

• Increase the donkeys (heart) efficiency

59
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

60
Cardiac Resynchronization Therapy

• Follow-up Care
• Standard medical management of HF by primary
  physician as defined by practice guidelines
• Device follow-up may be performed by physician
  specializing in implantable devices

61
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 20023461845-53
62
Cardiac Resynchronization Therapy Creating
Realistic Patient Expectations

• Have patients set their own goals of what they
  would like to do following CRT
• Grocery shopping
• Decreasing Lasix dose
• Walking to the mailbox without stopping
• Lying flat to sleep
• Encourage them to be part of the group that
  responds to their therapy

63
First Medical Follow-up Visit

• 7-10 Days Post-implant
• Follow daily weights closely
• Check wound site
• Physical Exam
• Assess volume status
• Patients typically over-diurese following CRT
• Ascertain quality of life
• Subtle improvements?
• Check electrolytes including BUN/Cr
• Give patients encouragement!

This is not a complete list for many
practitioners and is presented here only as a
guideline.
64
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

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Brief Statement for Cardiac Resynchronization
System (InSync 8040 Generator / InSync ICD 7272
/ Attain Models 2187, 2188, 4193 Leads /
9790/2090 Programmer )

• Indications
• -          The Medtronic InSync device is
  indicated for the reduction of the symptoms of
  moderate to severe heart failure (NYHA Functional
  Class III or IV) in those patients who remain
  symptomatic despite stable, optimal medical
  therapy, and have a left ventricular ejection
  fraction less than or equal to 35 and a QRS
  duration greater than or equal to 130ms. The
  InSync ICD system is, also, intended to provide
  ventricular antitachycardia pacing and
  ventricular defibrillation for automated
  treatment of life threatening ventricular
  arrhythmia.
• -          The Medtronic Models 9790 and 2090
  Programmers are portable, microprocessor-based
  instruments used to program Medtronic implantable
  devices.
• -          The Attain Left heart leads have
  application as part of a Medtronic biventricular
  pacing system.
•  
• Contraindications
• -          Asynchronous pacing is contraindicated
  in the presence (or likelihood) of competitive or
  intrinsic rhythms.
• -          Unipolar pacing is contraindicated in
  patients with an implanted defibrillator or
  cardioverter-defibrillator (ICD) because it may
  cause unwanted delivery or inhibition of
  defibrillator or ICD therapy.
•           The InSync ICD is contraindicated in
  patients whose ventricular tachyarrhythmias may
  have transient or reversible causes, or for
  patients with incessant VT or VF.
•           The Attain Models 2187, 2188, and 4193
  leads are contraindicated for patients with
  coronary venous vasculature that is inadequate
  for lead placement, as indicated by venogram.
• -          Do not use steroid eluting leads in
  patients for whom a single dose of 1.0 mg
  dexamethasone sodium phosphate may be
  contraindicated.
•  
• Warnings and Precautions
• -          Patients should avoid sources of
  magnetic resonance imaging, diathermy, high
  sources of radiation, electrosurgical cautery,
  external defibrillation, lithotripsy, and
  radiofrequency ablation. These may result in
  underdetection of VT/VF, inappropriate therapy
  delivery, and/or electrical reset of the device.
• -          Certain programming and device
  operations may not provide cardiac
  resynchronization.
• -          The InSync Elective Replacement
  Indicator (ERI) results in the device switching
  to VVI pacing at 65 ppm. For this reason, the
  device should be replaced prior to ERI being set.
• -          An implantable defibrillator may be
  implanted concomitantly with an InSync system,
  provided implant protocols are followed.
• -          Leads, stylets and guide wires should
  be handled with great care, their use may cause
  trauma to the heart. When using a Model 4193
  lead, only use compatible stylets (stylets with
  downsized knobs and are 3 cm shorter than the
  lead length).
• -          Chronic repositioning or removal of
  leads may be difficult because of fibrotic tissue
  development.