Hf etiology-dx-rx

A Guide to the Etiology, A Guide to the Etiology, Pathophysiology, Diagnosis, Pathophysiology, Diagnosis,

and Treatment of Heart Failureand Treatment of Heart Failure

Created in association with Created in association with Dr. Philip B. Adamson, DirectorDr. Philip B. Adamson, Director

Congestive Heart Failure Treatment ProgramCongestive Heart Failure Treatment ProgramUniversity of OklahomaUniversity of Oklahoma

Oklahoma City, OklahomaOklahoma City, Oklahoma

This presentation is provided for educational purposes This presentation is provided for educational purposes only and should not be considered the only source only and should not be considered the only source

for this type of information. At all times, it is the for this type of information. At all times, it is the professional decision of the practitioner to exercise professional decision of the practitioner to exercise

independent judgment in a particular situation.independent judgment in a particular situation.

Objectives:Objectives:

Upon completing the session, the participant will be Upon completing the session, the participant will be able to:able to:• Describe the incidence and prevalence of heart failureDescribe the incidence and prevalence of heart failure

• List the common etiologies of heart failureList the common etiologies of heart failure

• Define the compensatory mechanisms that occur due to Define the compensatory mechanisms that occur due to heart failureheart failure

• Identify current assessment and treatment modalities for Identify current assessment and treatment modalities for heart failure patientsheart failure patients

• Describe Cardiac Resynchronization Therapy (CRT) and Describe Cardiac Resynchronization Therapy (CRT) and the patient population indicated for CRT devicesthe patient population indicated for CRT devices

Part I: Part I: Etiology and Pathophysiology of Etiology and Pathophysiology of

Heart FailureHeart Failure

Heart Failure (HF) DefinitionHeart Failure (HF) Definition

A complex clinical syndrome in which the heart is A complex clinical syndrome in which the heart is incapable of maintaining a cardiac output adequate incapable of maintaining a cardiac output adequate to accommodate metabolic requirements and the to accommodate metabolic requirements and the venous return.venous return.

1 World Health Statistics, World Health Organization, 1995.1 World Health Statistics, World Health Organization, 1995.

2 American Heart Association, 2002 Heart and Stroke Statistical Update.2 American Heart Association, 2002 Heart and Stroke Statistical Update.

HF Incidence and PrevalenceHF Incidence and Prevalence

• Prevalence Prevalence – Worldwide, 22 millionWorldwide, 22 million11

– United States, 5 millionUnited States, 5 million22

• Incidence Incidence – Worldwide, 2 million new cases annuallyWorldwide, 2 million new cases annually11

– United States, 500,000 new cases annuallyUnited States, 500,000 new cases annually22

• HF afflicts 10 out of every 1,000 over age 65 in HF afflicts 10 out of every 1,000 over age 65 in the U.S.the U.S.22

Prevalence of HF by Age and GenderPrevalence of HF by Age and Gender

United States: 1988-94United States: 1988-94

0

2

4

6

8

10

Percent of Population

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

New York Heart Association New York Heart Association Functional ClassificationFunctional Classification

Class I:Class I: No symptoms with ordinary activityNo symptoms with ordinary activity

Class II:Class II: Slight limitation of physical activity. Comfortable at rest, Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, but ordinary physical activity results in fatigue, palpitation, dyspnea, or anginapalpitation, dyspnea, or angina

Class III:Class III: Marked limitation of physical activity. Comfortable at Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in rest, but less than ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal painfatigue, palpitation, dyspnea, or anginal pain

Class IV:Class IV: Unable to carry out any physical activity without Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency may be discomfort. Symptoms of cardiac insufficiency may be present even at restpresent even at rest

HF Classification: Evolution and HF Classification: Evolution and Disease ProgressionDisease Progression

• Four Stages of HF (ACC/AHA Guidelines):Four Stages of HF (ACC/AHA Guidelines):

Stage A: Patient at high risk for developing HF with no Stage A: Patient at high risk for developing HF with no structural disorder of the heartstructural disorder of the heart

Stage B: Patient with structural disorder without symptoms Stage B: Patient with structural disorder without symptoms of HFof HF

Stage C: Patient with past or current symptoms of HF Stage C: Patient with past or current symptoms of HF associated with underlying structural heart diseaseassociated with underlying structural heart disease

Stage D: Patient with end-stage disease who requires Stage D: Patient with end-stage disease who requires specialized treatment strategiesspecialized treatment strategies

Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001Chronic Heart Failure in the Adult, 2001

MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized 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). intervention trial in congestive heart failure (MERIT-HF). LANCET. LANCET. 1999;353:2001-07.1999;353:2001-07.

Severity of Heart FailureSeverity of Heart FailureModes of DeathModes of Death

12%12%

24%24%

64%64%

CHFCHF

OtherOther

SuddenSuddenDeathDeath

n = 103n = 103

NYHA IINYHA II

26%26%

15%15%

59%59%

CHFCHF

OtherOther


n = 103n = 103

NYHA IIINYHA III

56%56%

11%11%

33%33%

CHFCHF

OtherOther


n = 27n = 27

NYHA IVNYHA IV

Etiology of Heart FailureEtiology of Heart Failure

What causes heart failure?What causes heart failure?• The loss of a critical quantity of functioning The loss of a critical quantity of functioning

myocardial cells after injury to the heart due to:myocardial cells after injury to the heart due to:– Ischemic Heart Disease Ischemic Heart Disease – Hypertension Hypertension – Idiopathic CardiomyopathyIdiopathic Cardiomyopathy– Infections (e.g., viral myocarditis, Chagas’ disease)Infections (e.g., viral myocarditis, Chagas’ disease)– Toxins (e.g., alcohol or cytotoxic drugs) Toxins (e.g., alcohol or cytotoxic drugs) – Valvular Disease Valvular Disease – Prolonged ArrhythmiasProlonged Arrhythmias

The Donkey Analogy The Donkey Analogy

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

30%30%

70%70%

Diastolic DysfunctionDiastolic DysfunctionSystolic DysfunctionSystolic Dysfunction

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

Left Ventricular DysfunctionLeft Ventricular Dysfunction

• Systolic:Systolic: Impaired contractility/ejection Impaired contractility/ejection– Approximately two-thirds of heart failure patients have systolic Approximately two-thirds of heart failure patients have systolic

dysfunctiondysfunction11

• Diastolic:Diastolic: Impaired filling/relaxation Impaired filling/relaxation

1 Lilly, L. 1 Lilly, L. Pathophysiology of Heart DiseasePathophysiology of Heart Disease. Second Edition p 200. Second Edition p 200

Cardiac OutputCardiac Output

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

Cardiac Output = HR x SVCardiac Output = HR x SV

StrokeStrokeVolumeVolume

PreloadPreload AfterloadAfterload

ContractilityContractility


Heart RateHeart Rate• Synergistic LV ContractionSynergistic LV Contraction• Wall IntegrityWall Integrity• Valvular CompetenceValvular Competence

Determinants of Ventricular FunctionDeterminants of Ventricular Function

Volume Volume OverloadOverload

Pressure Pressure OverloadOverload

Loss of Loss of MyocardiumMyocardium

Impaired Impaired ContractilityContractility

LV DysfunctionLV DysfunctionEF < 40%EF < 40%

Cardiac Cardiac OutputOutput

Hypoperfusion Hypoperfusion

End Systolic Volume End Systolic Volume

End Diastolic Volume End Diastolic Volume

Pulmonary Congestion Pulmonary Congestion

Left Ventricular DysfunctionLeft Ventricular Dysfunction

Hemodynamic Basis for Hemodynamic Basis for Heart Failure SymptomsHeart Failure Symptoms

Hemodynamic Basis forHemodynamic Basis forHeart Failure SymptomsHeart Failure Symptoms

LVEDP LVEDP

Left Atrial Pressure Left Atrial Pressure

Pulmonary Capillary Pressure Pulmonary Capillary Pressure

Pulmonary CongestionPulmonary Congestion

Left Ventricular DysfunctionLeft Ventricular DysfunctionSystolic and DiastolicSystolic and Diastolic

• SymptomsSymptoms

– Dyspnea on ExertionDyspnea on Exertion

– Paroxysmal Nocturnal Paroxysmal Nocturnal DyspneaDyspnea

– TachycardiaTachycardia

– CoughCough

– HemoptysisHemoptysis

• Physical SignsPhysical Signs

– Basilar RalesBasilar Rales

– Pulmonary EdemaPulmonary Edema

– S3 GallopS3 Gallop

– Pleural EffusionPleural Effusion

– Cheyne-Stokes RespirationCheyne-Stokes Respiration

Right Ventricular FailureRight Ventricular FailureSystolic and DiastolicSystolic and Diastolic

• SymptomsSymptoms

– Abdominal PainAbdominal Pain

– AnorexiaAnorexia

– NauseaNausea

– BloatingBloating

– SwellingSwelling

• Physical SignsPhysical Signs

– Peripheral EdemaPeripheral Edema

– Jugular Venous DistentionJugular Venous Distention

– Abdominal-Jugular RefluxAbdominal-Jugular Reflux

– HepatomegalyHepatomegaly

Consequences of DecreasedConsequences of DecreasedMean Arterial PressureMean Arterial Pressure

Mean Arterial Pressure (BP)Mean Arterial Pressure (BP)

==


xx

Total Peripheral ResistanceTotal Peripheral Resistance

Compensatory MechanismsCompensatory Mechanisms

• Frank-Starling MechanismFrank-Starling Mechanism

• Neurohormonal ActivationNeurohormonal Activation

• Ventricular RemodelingVentricular Remodeling


Frank-Starling MechanismFrank-Starling Mechanism

a.a. At rest, no HFAt rest, no HF

b.b. HF due to LV systolic dysfunctionHF due to LV systolic dysfunction

c.c. Advanced HFAdvanced HF

Compensatory Mechanisms Compensatory Mechanisms

Neurohormonal ActivationNeurohormonal Activation

Many different hormone systems are involved in Many different hormone systems are involved in maintaining normal cardiovascular homeostasis, maintaining normal cardiovascular homeostasis, including:including:

• Sympathetic nervous system (SNS)Sympathetic nervous system (SNS)

• Renin-angiotensin-aldosterone system (RAAS)Renin-angiotensin-aldosterone system (RAAS)

• Vasopressin (a.k.a. antidiuretic hormone, ADH)Vasopressin (a.k.a. antidiuretic hormone, ADH)

MAP = (MAP = (SV x SV x HR) x HR) x TPRTPR

Sympathetic Nervous SystemSympathetic Nervous System

ContractilityContractility TachycardiaTachycardia VasoconstrictionVasoconstriction

Compensatory Mechanisms: Compensatory Mechanisms: Sympathetic Nervous SystemSympathetic Nervous System

Decreased MAPDecreased MAP

Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52.

CNS sympathetic outflowCNS sympathetic outflow

Disease progressionDisease progression

Cardiac sympatheticCardiac sympatheticactivityactivity

11--

receptorsreceptors22--

receptorsreceptors11--

receptorsreceptors

VasoconstrictionVasoconstrictionSodium retentionSodium retention

Myocardial toxicityMyocardial toxicityIncreased arrhythmiasIncreased arrhythmias

SympatheticSympatheticactivity to kidneysactivity to kidneys

+ peripheral vasculature+ peripheral vasculature

ActivationActivationof RASof RAS

11-- 11--

Sympathetic Activation in Heart FailureSympathetic Activation in Heart Failure

VasoconstrictionVasoconstriction

Oxidative StressOxidative Stress

Cell GrowthCell Growth ProteinuriaProteinuria

LV remodelingLV remodeling

Vascular remodelingVascular remodeling

AngiotensinogenAngiotensinogen

Angiotensin IAngiotensin I

Angiotensin IIAngiotensin II

AT I receptorAT I receptor

ReninRenin

AngiotensinAngiotensinConvertingConverting

EnzymeEnzyme

Compensatory Mechanisms: Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS)Renin-Angiotensin-Aldosterone (RAAS)

MAP = (MAP = (SV x SV x HR) x HR) x TPRTPR

Renin-Angiotensin-AldosteroneRenin-Angiotensin-Aldosterone(( renal perfusion) renal perfusion)

Salt-water retentionSalt-water retentionThirstThirst

SympatheticSympatheticaugmentationaugmentation VasoconstrictionVasoconstriction

Compensatory Mechanisms: Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS)Renin-Angiotensin-Aldosterone (RAAS)

Decreased systemic blood pressureDecreased systemic blood pressure

Central baroreceptorsCentral baroreceptors

Stimulation of hypothalamus, which producesStimulation of hypothalamus, which producesvasopressin for release by pituitary glandvasopressin for release by pituitary gland

Release of vasopressin by pituitary glandRelease of vasopressin by pituitary glandVasoconstrictionVasoconstriction

Increased systemic blood pressureIncreased systemic blood pressure

--

Compensatory Mechanisms: Compensatory Mechanisms: Neurohormonal Activation – VasopressinNeurohormonal Activation – Vasopressin

Compensatory Neurohormonal Stimulation: Compensatory Neurohormonal Stimulation: Summary Summary

Decreased Cardiac OutputDecreased Cardiac Output

SympatheticSympatheticnervous systemnervous system

Renin-angiotensinRenin-angiotensinsystemsystem

Antidiuretic hormoneAntidiuretic hormone(vasopressin)(vasopressin)

HeartHeartraterate

ContractilityContractility VasoconstrictionVasoconstriction Circulating volumeCirculating volume

AnteriolarAnteriolar

MaintainMaintainbloodblood

pressurepressure

CardiacCardiacoutputoutput

StrokeStrokevolumevolume

++

--++

VenousVenous

Venous return Venous return to heartto heart

(( preload)preload)

Peripheral edemaPeripheral edemaand pulmonaryand pulmonary

congestioncongestion

Curry CW, et al. Mechanical dyssynchrony in dilated cardiomyopathy with intraventricular conduction 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. delay as depicted by 3D tagged magnetic resonance imaging. Circulation 2000 Jan 4;101(1):E2.


Ventricular RemodelingVentricular Remodeling

Alterations in the heart’s size, shape, structure, and function brought about Alterations in the heart’s size, shape, structure, and function brought about by the chronic hemodynamic stresses experienced by the failing heart.by the chronic hemodynamic stresses experienced by the failing heart.

Other NeurohormonesOther Neurohormones

• Natriuretic Peptides: Three known typesNatriuretic Peptides: Three known types

– Atrial Natriuretic Peptide (ANP)Atrial Natriuretic Peptide (ANP)

• Predominantly found in the atriaPredominantly found in the atria

• Diuretic and vasodilatory propertiesDiuretic and vasodilatory properties

– Brain Natriuretic Peptide (hBNP) Brain Natriuretic Peptide (hBNP)

• Predominantly found in the cardiac ventricles Predominantly found in the cardiac ventricles

• Diuretic and vasodilatory propertiesDiuretic and vasodilatory properties

– C-type Natriuretic Peptide (CNP)C-type Natriuretic Peptide (CNP)

• Predominantly found in the central nervous systemPredominantly found in the central nervous system

• Limited natriuretic and vasodilatory propertiesLimited natriuretic and vasodilatory properties

Hemodynamic Hemodynamic (balanced vasodilation)(balanced vasodilation)

•• veinsveins

•• arteriesarteries

•• coronary arteriescoronary arteries

NeurohormonalNeurohormonal

aldosteronealdosterone

norepinephrinenorepinephrine

RenalRenal

diuresis & natriuresisdiuresis & natriuresis

DR I

M

K

RG

S SS

SG

L

GF

CC

S S

GSGQVM

K V LR

RH

KPS

Pharmacological Actions of hBNPPharmacological Actions of hBNP

Abraham WT and Schrier RW, 1994Abraham WT and Schrier RW, 1994

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

Endothelium-derived relaxing factors (EDRF) – Vasodilators:Endothelium-derived relaxing factors (EDRF) – Vasodilators:

• Nitric Oxide (NO)Nitric Oxide (NO)

• BradykininBradykinin

• ProstacyclinProstacyclin

Endothelium-derived constricting factors (EDCF) – Endothelium-derived constricting factors (EDCF) – Vasoconstrictors:Vasoconstrictors:

• Endothelin IEndothelin I

Endothelium-Derived Vasoactive SubstancesEndothelium-Derived Vasoactive Substances

Mediators of Heart FailureMediators of Heart Failure

CytokinesCytokines

• Small protein molecules produced by a variety of tissues Small protein molecules produced by a variety of tissues and cellsand cells

• Negative inotropesNegative inotropes

• Elevated levels associated with worse clinical outcomesElevated levels associated with worse clinical outcomes

• Examples:Examples:– Tumor necrosis factor (TNF)-alphaTumor necrosis factor (TNF)-alpha– Interleukin 1-alphaInterleukin 1-alpha– Interleukin-2Interleukin-2– Interleukin-6Interleukin-6– Interferon-alphaInterferon-alpha

LV DysfunctionLV Dysfunction

Decreased cardiac outputDecreased cardiac outputand and

Decreased blood pressureDecreased blood pressure

Frank-Starling MechanismFrank-Starling MechanismRemodelingRemodeling

Neurohormonal activationNeurohormonal activation

Increased cardiac output (via increasedIncreased cardiac output (via increasedcontractility and heart rate)contractility and heart rate)

Increased blood pressure (via vasoconstrictionIncreased blood pressure (via vasoconstriction and increased blood volume) and increased blood volume)

Increased cardiac workloadIncreased cardiac workload(increased preload and afterload)(increased preload and afterload)

Vicious Cycle of Heart FailureVicious Cycle of Heart Failure

Initially Adaptive, Deleterious if SustainedInitially Adaptive, Deleterious if Sustained

ResponseResponseShort-Term Short-Term EffectsEffects

Long-Term EffectsLong-Term Effects

Salt and Water RetentionSalt and Water Retention Augments PreloadAugments Preload Pulmonary Congestion, Pulmonary Congestion, AnasarcaAnasarca

VasoconstrictionVasoconstriction Maintains BP for perfusion Maintains BP for perfusion of vital organsof vital organs

Exacerbates pump Exacerbates pump dysfunction (excessive dysfunction (excessive afterload), increases afterload), increases cardiac energy cardiac energy expenditureexpenditure

Sympathetic StimulationSympathetic Stimulation Increases HR and ejectionIncreases HR and ejection Increases energy Increases energy expenditureexpenditure

Neurohormonal Responses to ImpairedNeurohormonal Responses to ImpairedCardiac PerformanceCardiac Performance

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

Part II:Part II:Assessing Heart FailureAssessing Heart Failure

Assessing Heart FailureAssessing Heart Failure

• Patient HistoryPatient History

• Physical ExaminationPhysical Examination

• Laboratory and Diagnostic TestsLaboratory and Diagnostic Tests

Diagnostic Evaluation of Diagnostic Evaluation of New Onset Heart FailureNew Onset Heart Failure

• Determine the type of cardiac dysfunction Determine the type of cardiac dysfunction (systolic vs. diastolic)(systolic vs. diastolic)

• Determine EtiologyDetermine Etiology

• Define prognosisDefine prognosis

• Guide therapyGuide therapy


Initial Work-up:Initial Work-up:

• ECGECG

• Chest x-rayChest x-ray

• Blood workBlood work

• Echocardiography Echocardiography

M-Mode EchoM-Mode Echo 2D Echo2D Echo

RARA

LALA

RVRVLVLV

SeptumSeptum

LV cavityLV cavity

LV WallLV Wall


Part III: Part III: Current Treatment Current Treatment

of Heart Failureof Heart Failure

The Vicious Cycle of The Vicious Cycle of Heart Failure ManagementHeart Failure Management

Chronic HFChronic HF

MD’s OfficeMD’s Office

Emergency Emergency RoomRoom

HospitalizationHospitalization

SOBSOB

WeightWeight

PO LasixPO LasixIV Lasix IV Lasix or Admitor Admit

Diurese & Diurese & HomeHome

General MeasuresGeneral Measures

Lifestyle Modifications:Lifestyle Modifications:

• Weight reductionWeight reduction

• Discontinue smokingDiscontinue smoking

• Avoid alcohol and other Avoid alcohol and other cardiotoxic substancescardiotoxic substances

• ExerciseExercise

Medical Considerations:Medical Considerations:

• Treat HTN, hyperlipidemia, Treat HTN, hyperlipidemia, diabetes, arrhythmiasdiabetes, arrhythmias

• Coronary revascularizationCoronary revascularization

• AnticoagulationAnticoagulation

• ImmunizationImmunization

• Sodium restrictionSodium restriction

• Daily weightsDaily weights

• Close outpatient monitoringClose outpatient monitoring

Pharmacologic ManagementPharmacologic Management

DigoxinDigoxin

• Enhances inotropy of cardiac muscleEnhances inotropy of cardiac muscle

• Reduces activation of SNS and RAASReduces activation of SNS and RAAS

• Controlled trials have shown long-term digoxin therapy:Controlled trials have shown long-term digoxin therapy:– Reduces symptomsReduces symptoms

– Increases exercise toleranceIncreases exercise tolerance

– Improves hemodynamicsImproves hemodynamics

– Decreases risk of HF progressionDecreases risk of HF progression

– Reduces hospitalization rates for decompensated HFReduces hospitalization rates for decompensated HF

– Does not improve survivalDoes not improve survival

Digitalis CompoundsDigitalis Compounds

Like the carrot placed in front of the donkeyLike the carrot placed in front of the donkey


DiureticsDiuretics

• Used to relieve fluid retentionUsed to relieve fluid retention

• Improve exercise toleranceImprove exercise tolerance

• Facilitate the use of other drugs indicated for heart failure Facilitate the use of other drugs indicated for heart failure

• Patients can be taught to adjust their diuretic dose based Patients can be taught to adjust their diuretic dose based on changes in body weighton changes in body weight

• Electrolyte depletion a frequent complicationElectrolyte depletion a frequent complication

• Should never be used alone to treat heart failureShould never be used alone to treat heart failure

• Higher doses of diuretics are associated with increased Higher doses of diuretics are associated with increased mortalitymortality


ACE Inhibitors ACE Inhibitors

• Blocks the conversion of angiotensin I to angiotensin II; Blocks the conversion of angiotensin I to angiotensin II; prevents functional deteriorationprevents functional deterioration

• Recommended for all heart failure patientsRecommended for all heart failure patients

• Relieves symptoms and improves exercise toleranceRelieves symptoms and improves exercise tolerance

• Reduces risk of death and decreases disease Reduces risk of death and decreases disease progressionprogression

• Benefits may not be apparent for 1-2 months after Benefits may not be apparent for 1-2 months after initiationinitiation

Diuretics, ACE InhibitorsDiuretics, ACE Inhibitors

Reduce the number of sacks on the wagonReduce the number of sacks on the wagon


Beta-BlockersBeta-Blockers

• Cardioprotective effects due to blockade of excessive SNS Cardioprotective effects due to blockade of excessive SNS stimulation stimulation

• In the short-term, beta blocker decreases myocardial In the short-term, beta blocker decreases myocardial contractility; increase in EF after 1-3 months of usecontractility; increase in EF after 1-3 months of use

• Long-term, placebo-controlled trials have shown Long-term, placebo-controlled trials have shown symptomatic improvement in patients treated with certain symptomatic improvement in patients treated with certain beta-blockersbeta-blockers11

• When combined with conventional HF therapy, beta-When combined with conventional HF therapy, beta-blockers reduce the combined risk of morbidity and blockers reduce the combined risk of morbidity and mortality, or disease progressionmortality, or disease progression11

1 Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management 1 Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001 p. 20.of Chronic Heart Failure in the Adult, 2001 p. 20.

ß-Blockersß-Blockers

Limit the donkey’s speed, thus saving energyLimit the donkey’s speed, thus saving energy


Aldosterone AntagonistsAldosterone Antagonists

• Generally well-toleratedGenerally well-tolerated

• Shown to reduce heart failure-related morbidity and Shown to reduce heart failure-related morbidity and mortality mortality

• Generally reserved for patients with NYHA Class III-IV HFGenerally reserved for patients with NYHA Class III-IV HF

• Side effects include hyperkalemia and gynecomastia. Side effects include hyperkalemia and gynecomastia. Potassium and creatinine levels should be closely Potassium and creatinine levels should be closely monitoredmonitored


Angiotensin Receptor Blockers (ARBs)Angiotensin Receptor Blockers (ARBs)

• Block ATBlock AT11 receptors, which bind circulating angiotensin II receptors, which bind circulating angiotensin II

• Examples: valsartan, candesartan, losartanExamples: valsartan, candesartan, losartan

• Should not be considered equivalent or superior to ACE Should not be considered equivalent or superior to ACE inhibitorsinhibitors

• In clinical practice, ARBs should be used to treat patients In clinical practice, ARBs should be used to treat patients who are ACE intolerant due to intractable cough or who who are ACE intolerant due to intractable cough or who develop angioedemadevelop angioedema

ATAT11 receptor receptor ATAT22 receptor receptor

• VasoconstrictionVasoconstriction

• Growth PromotionGrowth Promotion

• Anti-apoptoticAnti-apoptotic

• Pro-fibroticPro-fibrotic

• Pro-thromboticPro-thrombotic

• Pro-oxidantPro-oxidant

• VasodilationVasodilation

• Growth inhibitionGrowth inhibition

• Pro-apoptoticPro-apoptotic

• ? Fibrosis? Fibrosis

• ? Thrombosis? Thrombosis

• ? redox? redox

Angiotensin II ReceptorsAngiotensin II Receptors

Part IV:Part IV:Assessment and Treatment of Assessment and Treatment of

the Heart Failure Patientthe Heart Failure Patient

Treatment Approach for the Patient Treatment Approach for the Patient with Heart Failurewith Heart Failure

Stage AStage A

At high risk, no At high risk, no structural diseasestructural disease

Stage BStage B

Structural heart Structural heart disease, disease,

asymptomaticasymptomatic

Stage DStage D

Refractory HF Refractory HF requiring requiring

specialized specialized interventionsinterventions

TherapyTherapy

• Treat HypertensionTreat Hypertension

• Treat lipid Treat lipid disordersdisorders

• Encourage regular Encourage regular exerciseexercise

• Discourage alcohol Discourage alcohol intakeintake

• ACE inhibitionACE inhibition

TherapyTherapy

• All measures All measures under stage Aunder stage A

• ACE inhibitors in ACE inhibitors in appropriate appropriate patientspatients

• Beta-blockers in Beta-blockers in appropriate appropriate patientspatients

TherapyTherapy

• All measures All measures under stage Aunder stage A

Drugs:Drugs:

• DiureticsDiuretics

• ACE inhibitorsACE inhibitors

• Beta-blockersBeta-blockers

• DigitalisDigitalis

• Dietary salt Dietary salt restrictionrestriction

TherapyTherapy

• All measures All measures under stages A,B, under stages A,B, and Cand C

• Mechanical assist Mechanical assist devicesdevices

• Heart Heart transplantationtransplantation

• Continuous (not Continuous (not intermittent) IV intermittent) IV inotropic infusions inotropic infusions for palliationfor palliation

• Hospice careHospice care

Stage CStage C

Structural heart Structural heart disease with disease with prior/current prior/current

symptoms of HFsymptoms of HF

Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001Chronic Heart Failure in the Adult, 2001

Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

Increase the donkeyIncrease the donkey’s’s (heart) efficiency (heart) efficiency

Patient IndicationsPatient Indications

CRT device:CRT device:

– Moderate to severe HF (NYHA Class III/IV) patients Moderate to severe HF (NYHA Class III/IV) patients

– Symptomatic despite optimal, medical therapySymptomatic despite optimal, medical therapy

– QRS QRS 130 msec 130 msec

– LVEF LVEF 35% 35%

CRT plus ICD:CRT plus ICD:

– Same as above with ICD indicationSame as above with ICD indication


Follow-up CareFollow-up Care

• Standard medical management of HF by primary Standard medical management of HF by primary physician as defined by practice guidelinesphysician as defined by practice guidelines

• Device follow-up may be performed by physician Device follow-up may be performed by physician specializing in implantable devicesspecializing in implantable devices


Cardiac Resynchronization Therapy: Cardiac Resynchronization Therapy: Creating Realistic Patient ExpectationsCreating Realistic Patient Expectations

• Approximately two-third of patients should Approximately two-third of patients should experience improvement (responders vs. experience improvement (responders vs. non-responders)non-responders)11

– Some patients may not experience immediate Some patients may not experience immediate improvementimprovement

Note: CRT is adjunctive and is not intended to replace medical therapy. Note: CRT is adjunctive and is not intended to replace medical therapy. Patients will continue to be followed by HF Specialist and Physician Patients will continue to be followed by HF Specialist and Physician managing implantable devices.managing implantable devices.

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

• Have patients set their own goals of what they would Have patients set their own goals of what they would like to do following CRT:like to do following CRT:– Grocery shoppingGrocery shopping

– Decreasing Lasix dose Decreasing Lasix dose

– Walking to the mailbox without stoppingWalking to the mailbox without stopping

– Lying flat to sleepLying flat to sleep

• Encourage them to be part of the group that responds Encourage them to be part of the group that responds to their therapyto their therapy

Cardiac Resynchronization Therapy: Cardiac Resynchronization Therapy: Creating Realistic Patient ExpectationsCreating Realistic Patient Expectations

First Medical Follow-up VisitFirst Medical Follow-up Visit

7-10 Days Post-implant7-10 Days Post-implant**

• Follow daily weights closelyFollow daily weights closely

• Check wound siteCheck wound site

• Physical ExamPhysical Exam

– Assess volume status Assess volume status

• Patients typically over-diurese following CRTPatients typically over-diurese following CRT

• Ascertain quality of lifeAscertain quality of life

– Subtle improvements?Subtle improvements?

• Check electrolytes including BUN/CrCheck electrolytes including BUN/Cr

• Give patients encouragement!Give patients encouragement!

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

SummarySummary

• Heart failure is a chronic, progressive disease that is Heart failure is a chronic, progressive disease that is generally not curable, but treatablegenerally not curable, but treatable

• Most recent guidelines promote lifestyle modifications and Most recent guidelines promote lifestyle modifications and medical management with ACE inhibitors, beta blockers, medical management with ACE inhibitors, beta blockers, digoxin, and diuretics digoxin, and diuretics

• It is estimated 15% of all heart failure patients may be It is estimated 15% of all heart failure patients may be candidates for cardiac resynchronization therapy (see later candidates for cardiac resynchronization therapy (see later section for details)section for details)

• Close follow-up of the heart failure patient is essential, with Close follow-up of the heart failure patient is essential, with necessary adjustments in medical managementnecessary adjustments in medical management

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

IndicationsIndications-- 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 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 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 130ms. The InSync ICD system is, also, intended to provide ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life threatening ventricular arrhythmia.arrhythmia.-- The Medtronic Models 9790 and 2090 Programmers are portable, microprocessor-based instruments used to program Medtronic implantable devices.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.The Attain Left heart leads have application as part of a Medtronic biventricular pacing system. ContraindicationsContraindications-- Asynchronous pacing is contraindicated in the presence (or likelihood) of competitive or intrinsic rhythms.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 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.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 The InSync ICD is contraindicated in patients whose ventricular tachyarrhythmias may have transient or reversible causes, or for patients with incessant VT or VF.VF. The Attain Models 2187, 2188, and 4193 leads are contraindicated for patients with coronary venous vasculature that is inadequate for lead placement, as 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.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.- 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 PrecautionsWarnings and Precautions-- Patients should avoid sources of magnetic resonance imaging, diathermy, high sources of radiation, electrosurgical cautery, external defibrillation, lithotripsy, 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 and radiofrequency ablation. These may result in underdetection of VT/VF, inappropriate therapy delivery, and/or electrical reset of the device.underdetection of VT/VF, inappropriate therapy delivery, and/or electrical reset of the device.-- Certain programming and device operations may not provide cardiac resynchronization.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 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.to ERI being set.-- An implantable defibrillator may be implanted concomitantly with an InSync system, provided implant protocols are followed.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 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).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.Chronic repositioning or removal of leads may be difficult because of fibrotic tissue development.-- Previously implanted pulse generators, implantable cardioverter-defibrillators, and leads should generally be explanted.Previously implanted pulse generators, implantable cardioverter-defibrillators, and leads should generally be explanted.-- Back-up pacing should be readily available during implant. Use of leads may cause heart block.Back-up pacing should be readily available during implant. Use of leads may cause heart block. See the appropriate technical manuals for detailed information regarding instructions for use, indications, contraindications, warnings and precautions, and potential adverse See the appropriate technical manuals for detailed information regarding instructions for use, indications, contraindications, warnings and precautions, and potential adverse events.events. Caution: Caution: Federal law (USA) restricts these devices to sale by or on the order of a physician.Federal law (USA) restricts these devices to sale by or on the order of a physician.

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