Heart FailureHeart Failure

Current ConceptsCurrent Concepts

Howard M. Weinberg, D.O. Howard M. Weinberg, D.O. F.A.C.CF.A.C.C..

Cardiac ArchitectureCardiac Architecture

UltrastructureUltrastructure

11. 75% total volume of the heart is made up of . 75% total volume of the heart is made up of cardiomyocytecardiomyocyte

2. Contractile proteins lie within the cardiomyocyte2. Contractile proteins lie within the cardiomyocyteA. Ventricular and atrial myocytesA. Ventricular and atrial myocytesB. Myofibrils form myocytes(contractile B. Myofibrils form myocytes(contractile

elements)elements)C. Myofibers are groups of C. Myofibers are groups of

myocytes.myocytes.

Contractile ProteinsContractile Proteins

1.1. Actin and MyosinActin and Myosin

2.2. Calcium interacts with Troponin CCalcium interacts with Troponin Crelieves the inhibition caused by relieves the inhibition caused by Troponin ITroponin I

Cardiac CycleCardiac Cycle

Three Phases:Three Phases:1) LV Contraction1) LV Contraction

2) LV Relaxation2) LV Relaxation

3) LV Filling3) LV Filling

The Cardiac CycleThe Cardiac CycleLV CONTRACTIONLV CONTRACTION

Isovolumic contraction(b)Isovolumic contraction(b) Maximal Ejection ©Maximal Ejection ©

LV RelaxationLV Relaxation

Start of relaxation andStart of relaxation and reduced ejection (d)reduced ejection (d) Isovolumic relaxation(e)Isovolumic relaxation(e) LV Filling: rapid phase (f) LV Filling: rapid phase (f) Slow LV Filling (g)Slow LV Filling (g) Atrial systole( a)Atrial systole( a)See Wiggers DiagramSee Wiggers Diagram

Frank-Starling Relationship

A.A. Preload: Load before contraction(venous Preload: Load before contraction(venous return) return)

B.B. Afterload: Load which the LV contracts Afterload: Load which the LV contracts against against

Starling CurveStarling Curve

HF DefinedHF Defined

““Heart failure is a complex clinical syndrome that Heart failure is a complex clinical syndrome that

can result from any structural can result from any structural

or functional cardiac disorder that impairs or functional cardiac disorder that impairs

the ability of the ventricle to fill with the ability of the ventricle to fill with

or eject blood with an increase in intracardiac or eject blood with an increase in intracardiac

chamber pressure”chamber pressure”

Hunt SA et al. Circulation. 2001;104:2996

Clinical Aspects of Heart FailureClinical Aspects of Heart Failure

Backward Heart FailureBackward Heart FailureLVEDP and LVEDV increaseLVEDP and LVEDV increaseLAP and LAV increase(atria contracts for LAP and LAV increase(atria contracts for

C.O.) C.O.) Venous and PCWP increaseVenous and PCWP increaseTransudation of fluid from capillary bed Transudation of fluid from capillary bed

Clinical Aspects of Heart FailureClinical Aspects of Heart Failure

Forward Heart FailureForward Heart FailureDecrease C.O.= decrease perfusion to vital Decrease C.O.= decrease perfusion to vital

organsorgans Increase Na and Water retentionIncrease Na and Water retention

Symptoms of Heart FailureSymptoms of Heart Failure

Exertional DyspneaExertional Dyspnea Orthopnea-Sx in the recumbent positionOrthopnea-Sx in the recumbent position Paroxysmal Nocturnal DyspneaParoxysmal Nocturnal Dyspnea

Theory: 1. Slow resorption of interstial Theory: 1. Slow resorption of interstial fluid fluid

2. Reduced adrenergic support 2. Reduced adrenergic support at nightat night

3. Normal nocturnal 3. Normal nocturnal depression of the respiratorydepression of the respiratory

center center

FraminghamFramingham Criteria for CHF Criteria for CHF

Cardiac vs Pulmonary DyspneaCardiac vs Pulmonary Dyspnea

Frequent coughingFrequent coughingCough productionCough productionFeverFeverDiaphoresisDiaphoresisResponse to TxResponse to Tx

Diastolic Heart FailureDiastolic Heart Failure

1.1. 1/3 of pts. have primary diastolic HF 1/3 of pts. have primary diastolic HF (normal or near normal LV function)(normal or near normal LV function)

2.2. 1/3 combined systolic and diastolic HF1/3 combined systolic and diastolic HF

3.3. Altered ventricular relaxation(inactivation Altered ventricular relaxation(inactivation of contraction)of contraction)

4.4. Alteration of ventricular fillingAlteration of ventricular filling

5.5. Some causes: myocardial ischemia, Some causes: myocardial ischemia, restrictive cardiomyopathy,pericardial restrictive cardiomyopathy,pericardial diseasedisease

Diastolic Heart FailureDiastolic Heart Failure

Impaired ability to accept blood and relax Impaired ability to accept blood and relax during diastoleduring diastole

Both types increase with age, African Both types increase with age, African AmericansAmericans

40-70% incidence more often female, 40-70% incidence more often female, obese, older HTN and less likely to have obese, older HTN and less likely to have CADCAD

Less symptomatic and lower morbidity and Less symptomatic and lower morbidity and mortalitymortality

High Output FailureHigh Output Failure

Usually occurs with some underlying heart Usually occurs with some underlying heart diseasedisease

Clinical conditions: Clinical conditions: AnemiaAnemia Systemic Ateriovenous Fistula-dialysis/traumaSystemic Ateriovenous Fistula-dialysis/trauma HyperthyroidismHyperthyroidism BeriberiBeriberi PagetsPagets Multiple myeloma/Pregnancy/Carcinoid/ renal diseaseMultiple myeloma/Pregnancy/Carcinoid/ renal disease Obesity/polycythemia veraObesity/polycythemia vera

Yancy CW, Strong M. Prim Care Spec Ed. 2002;6:15

High Risk: Hypertension, coronary artery disease, diabetes, family history of cardiomyopathy

Asymptomatic LVD: Previous MI, LV systolic dysfunction, asymptomatic valvular disease

Symptomatic HF: Known structuralheart disease, shortness of breath and

fatigue, reduced exercise tolerance

RefractoryEnd-Stage HF:

Marked symptomsat rest despite maximal

medical therapy

AA

BB

CC

DD

Disease Progression of HF: Disease Progression of HF: ACC/AHA HF StagesACC/AHA HF Stages

EpidemiologyEpidemiology

Only major Only major cardiovascular cardiovascular disorder increasing in disorder increasing in incidence and incidence and prevalenceprevalence

Leading cause of Leading cause of hospitalization in >65hospitalization in >65

1/3 hospitalized 1/3 hospitalized patients readmitted in patients readmitted in 90 days90 days

5% of all hospital 5% of all hospital admissionsadmissions

Heart Failure is a Major and Growing Public Health Problem in the U.S.

Approximately 5 million patients in this country have HF

Over 550,000 patients are diagnosed with HF for the first time each year

Primary reason for 12 to 15 million office visits and 6.5 million hospital days each year

In 2001, nearly 53,000 patients died of HF as a primary cause

Mortality/MorbidityMortality/Morbidity

Despite therapeutic Despite therapeutic advances, the 1 year advances, the 1 year mortality for NYHA mortality for NYHA class IV approaches class IV approaches 40%40%

Impaired Quality of Impaired Quality of life.life.

Psychological distressPsychological distress Reduced social Reduced social

functioningfunctioning 49% admitted after 49% admitted after

an emotional eventan emotional event

Prevalence of HF Increases Prevalence of HF Increases With AgeWith Age

US, 1988–1994AHA. Heart Disease and Stroke Statistics—2004 Update

0

2

4

6

8

10

20–24 25–34 35–44 45–54 55–64 65–74 75+

Age (yr)

Pop

ulat

ion

(%)

Males

Females

Number of Patients Number of Patients With HF IncreasingWith HF Increasing

1979–20011979–2001 Hospital discharges from HF rose 164% from Hospital discharges from HF rose 164% from

377,000 to 995,000377,000 to 995,000 Deaths increased 155%Deaths increased 155%

As US population ages, number of patients As US population ages, number of patients with HF expected to double in 30 yrwith HF expected to double in 30 yr

AHA. Heart Disease and Stroke Statistics—2004 UpdateMassie BM et al. Am Heart J. 1997;133:703

Natural History of HFNatural History of HFS

urv

iva

l (%

)

LV Dysfunction and Symptoms

Mechanism of DeathSudden death 40%Worsened HF 40%Other 20%Progression

Annual Mortality

0%

100%

Asymptomatic Mild Moderate Severe

<5% 10% 20%–30% 30%–80%

Treatment of Heart FailureTreatment of Heart Failure

Non-surgicalNon-surgicalSpecialty ClinicsSpecialty ClinicsLifestyle ModificationLifestyle ModificationPharmacologicalPharmacological

SurgicalSurgical

Contributing Factors to ADHFContributing Factors to ADHF

Cardiovascular FactorsCardiovascular Factors Superimposed ischemia or infarctionSuperimposed ischemia or infarction Uncontrolled hypertensionUncontrolled hypertension Unrecognized primary valvular diseaseUnrecognized primary valvular disease Worsening secondary mitral regurgitationWorsening secondary mitral regurgitation New onset or uncontrolled atrial fibrillationNew onset or uncontrolled atrial fibrillation Excessive tachycardia or bradycardiaExcessive tachycardia or bradycardia Pulmonary embolismPulmonary embolism

Stevenson LW et al. Am Heart J. 1998;135:293

Contributing Factors to ADHF Contributing Factors to ADHF cont'dcont'd

Systemic FactorsSystemic Factors Inappropriate medicationsInappropriate medications Superimposed infectionSuperimposed infection AnemiaAnemia Uncontrolled diabetesUncontrolled diabetes Thyroid dysfunctionThyroid dysfunction Electrolyte abnormalitiesElectrolyte abnormalities PregnancyPregnancy

Stevenson LW et al. Am Heart J. 1998;135:293

Contributing Factors to ADHF Contributing Factors to ADHF cont'dcont'd

Patient-Related FactorsPatient-Related Factors Medication nonadherenceMedication nonadherence Dietary indiscretionDietary indiscretion Alcohol consumptionAlcohol consumption Substance abuseSubstance abuse

Stevenson LW et al. Am Heart J. 1998;135:293

Proven Outcomes for HF Proven Outcomes for HF TherapiesTherapies

Improve SurvivalImprove Survival ACE inhibitorACE inhibitor ARBARB Beta blockerBeta blocker Aldosterone receptor Aldosterone receptor

antagonistantagonist Hydralazine/long-Hydralazine/long-

acting nitratesacting nitrates

Reduce HospitalizationReduce Hospitalization ACE inhibitorACE inhibitor ARBARB Beta blockerBeta blocker Aldosterone receptor Aldosterone receptor

antagonistantagonist Hydralazine/long-acting Hydralazine/long-acting

nitratesnitrates DigoxinDigoxin

Surgical/Interventional TherapySurgical/Interventional Therapy

Cardiac Resynchronization TherapyCardiac Resynchronization TherapyRevascularizationRevascularizationValue repair/replacementValue repair/replacementCardiomyoplastyCardiomyoplastyVentricular ReductionVentricular ReductionLeft Ventricular Assist DevicesLeft Ventricular Assist DevicesTransplantTransplant

Ventricular RemodelingVentricular RemodelingVentricular Remodeling After Acute Infarction

Ventricular Remodeling in Diastolic and Systolic HF

Initial infarct

Expansion of infarct(hours to days)

Global remodeling(days to months)

Normal heart

Hypertrophied heart(diastolic HF)

Dilated heart(systolic HF)

Jessup M et al. N Engl J Med. 2003;348:2007

Yancy CW, Strong M. Prim Care Spec Ed. 2002;6:15

PLUS inotropes, transplant, ventricular assist device

Treat hypertension and lipids, smoking cessation, exercise, limit alcohol, ACE inhibitors in appropriate populations

PLUS ACE inhibitors, beta blockers in appropriate populations

PLUS ACE inhibitors, beta blockers, diuretics, digoxin, aldosterone receptor antagonists, dietary salt restriction

HF TherapyHF Therapy

Approach to the Patient withApproach to the Patient withCHFCHF

A ce-In h ib ito rB e ta B ocker

D ig oxin

D iu re tict itra te to eu vo lem ia

S ig n s an d sym p om s o f flu id re ten tion

A ce-In h ib ito rB e ta B ocker

D ig oxin

N o S ig n s an d S ym p tom s o f flu id re ten tion

A ssessm en t o f V o lu m e S ta tu s

E jec tion F rac tion< 4 0 %

A ssessm en t o f L V F u n c tionE ch o , M u g a

Neurohormonal Activation Neurohormonal Activation in Heart Failurein Heart Failure

M orb id ity/M orta lityA rrh yth m ias

P u m p F a ilu re

L V R em od e lin gan d

p rog ress ive L V D ys fu n c tion

F ib ros is , ap op tos is , h yp ertrop h yce llu la r/m o lecu la r a lte ra tion s ,

m yotoxic ity

H eart F a ilu re S ym tom sD ysp n ea

F atig u e ,E d em aC h es t C on g es tion

P erip h era l vasocon s tric tionH em od yn am ic a lte ra tion s

A c tiva tion o f R A S an d S N S

L V D ys fu n c tionIn c rease w a ll s tress

M yocard ia l In ju ry(C A D ,H TN ,C M P )

Background on RemodellingBackground on RemodellingAcute infarctionAcute infarction

(hours)(hours)Infarct expansionInfarct expansion(hours to days)(hours to days)

Global remodellingGlobal remodelling(days to months)(days to months)

Improvement of LV remodelling has been Improvement of LV remodelling has been associated with improvement in mortality and associated with improvement in mortality and morbidity outcomes in CHFmorbidity outcomes in CHF

B-Adrenergic Receptor BlockersB-Adrenergic Receptor Blockers

Improve survivalImprove survival Improve ejection fractionImprove ejection fractionRemodelingRemodelingQuality of lifeQuality of lifeReduce SCDReduce SCD Inhibiting adverse effects of the Inhibiting adverse effects of the

sympathetic nervous systemsympathetic nervous systemDiminish RAAS activationDiminish RAAS activation

All-Cause Mortality: MERIT-HFAll-Cause Mortality: MERIT-HF

MERIT-HF Study Group. Lancet. 1999;353:2001

P=0.0082 (adjusted)P=0.00009 (nominal)

PlaceboMetoprolol CR/XL

0

5

10

15

20

0 3 6 9 12 15 18 21

Follow-up (mo)

Cu

mu

lati

ve M

ort

alit

y (

%)

Cumulative Mortality in Patients Cumulative Mortality in Patients With Severe HF: With Severe HF: COPERNICUSCOPERNICUS

Packer M et al. N Engl J Med. 2001;344:1651

PlaceboPlacebo 11331133 937937 703703 580580 446446 286286 183183 114114CarvedilolCarvedilol 11561156 947947 733733 620620 479479 321321 208208 142142

No. of Patients at Risk

Carvedilol(n = 1156)

Placebo(n = 1133)

0

60

80

90

100

0

Months

Su

rviv

al (

% o

f P

ati

ents

)

3 6 9 12 15 18 21

70

P=0.0014 (adjusted)P=0.00013 (unadjusted)

Angiotensin-Converting InhibitorsAngiotensin-Converting Inhibitors

Decrease conversion of angiotensin I-IIDecrease conversion of angiotensin I-II Improve survivalImprove survivalDecrease rate of hospitalizationDecrease rate of hospitalization Improve symptomsImprove symptoms Inhibit neurohormonal activationInhibit neurohormonal activationReverse remodelingReverse remodelingDecrease incidence of SCD?Decrease incidence of SCD?

Cumulative Mortality in Patients Cumulative Mortality in Patients With Symptomatic HF: SOLVD With Symptomatic HF: SOLVD

P=0.0036 for comparison between groups by log-rank testSOLVD Investigators. N Engl J Med. 1991;325:293

Enalapril(n = 1285)

(n = 1284)Placebo

P=0.0036

0

10

20

30

40

50

0 6 12 18 24 30 36 42 48

Months

Mo

rtal

ity

(%)

PlaceboPlacebo 12841284 11591159 10851085 10051005 939939 819819 669669 487487 299299EnalaprilEnalapril 12851285 11951195 11271127 10691069 10101010 891891 697697 526526 333333

No. of Patients at Risk

DIGOXIN

NEUROHORMONAL EFFECTSDIGOXIN

NEUROHORMONAL EFFECTS

Plasma Noradrenaline

Peripheral nervous system activity

RAAS activity

Vagal tone

Normalizes arterial baroreceptors

Plasma Noradrenaline

Peripheral nervous system activity

RAAS activity

Vagal tone

Normalizes arterial baroreceptors

%WORSENING

OF CHF

%WORSENING

OF CHFp = 0.001p = 0.001DIGOXIN: 0.125 - 0.5 mg /d

(0.7 - 2.0 ng/ml)EF < 35%Class I-III (digoxin+diuretic+ACEI)Also significantly decreased exercisetime and LVEF.

DIGOXIN: 0.125 - 0.5 mg /d (0.7 - 2.0 ng/ml)EF < 35%Class I-III (digoxin+diuretic+ACEI)Also significantly decreased exercisetime and LVEF.

DIGOXIN EFFECT ON CHF PROGRESSION

DIGOXIN EFFECT ON CHF PROGRESSION

RADIANCEN Engl J Med 1993;329:1RADIANCEN Engl J Med 1993;329:1

Placebo n=93DIGOXIN Withdrawal

Placebo n=93DIGOXIN Withdrawal

DIGOXIN n=85DIGOXIN n=85

3030

1010

00

2020

1001008080202000 4040 6060DaysDays

All-Cause Mortality: DigoxinAll-Cause Mortality: Digoxin

DIG Investigation Group. N Engl J Med 1997;336:525

P=0.80

Placebo

Digoxin

0

10

20

30

40

50

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Mo

rtal

ity

Fro

m A

ny

Cau

se (

%)

Months

PlaceboPlacebo 34033403 32393239 31053105 29762976 28682868 27582758 26522652 25512551 22052205 18811881 15061506 11681168 734734 339339DigoxinDigoxin 33973397 32693269 31443144 30193019 28822882 27592759 26442644 25312531 21842184 18401840 14751475 11561156 737737 335335

No. of Patients at Risk

ARB in Heart FailureARB in Heart Failure(meta-analysis(meta-analysis))

17 Trials, 12,469pts (JACC Feb 2002)17 Trials, 12,469pts (JACC Feb 2002) No superiority of ARBs in reducing all-cause No superiority of ARBs in reducing all-cause

mortality or hospitalizations for heart failuremortality or hospitalizations for heart failure Poss. benefit with combination ace inhibitionPoss. benefit with combination ace inhibition Beneficial for pts intolerant to ace inhibitionBeneficial for pts intolerant to ace inhibition

ALDOSTERONEALDOSTERONE

Retention Na+

Retention H2O

Excretion K+

Excretion Mg2+

Retention Na+

Retention H2O

Excretion K+

Excretion Mg2+

Collagen

deposition

Fibrosis - myocardium

- vessels

SpironolactoneSpironolactone

Edema Edema

Arrhythmias Arrhythmias

Competitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney)

Competitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney)

ALDOSTERONE INHIBITORSALDOSTERONE INHIBITORS

RALES: All-Cause MortalityRALES: All-Cause Mortality1.00

0.95

0.90

0.85

0.80

0.75

0.70

0.65

0.60

0.55

0.50

0.45

0 3 6 9 12 15 18 21 24 27 30 33 36

Risk Reduction 30%95% Cl (18%-40%)P<0.001

Spironolactone+ standard therapy

Standard therapy(ACE inhibitor + loopdiuretic ± digoxin)

Probability of survival

MonthsPitt B, Zannad F, Remme WJ, et al. N Engl J Med, 1999;341:709-717.

00

2020

4040

6060

8080

>4 cm/m>4 cm/m22 <4 cm/m<4 cm/m22 LV IndexLV Index

2-Y

ear

Mo

rtal

ity

(%)

2-Y

ear

Mo

rtal

ity

(%) P = 0.004P = 0.004

Lee TH et al. Am J Cardiol 1993Lee TH et al. Am J Cardiol 1993

Relation Between LV Size Relation Between LV Size and Outcome in CHFand Outcome in CHF

M-mode echocardiography was performed on 382 M-mode echocardiography was performed on 382 patients with class III or IV HF (mean LVEF=20%)patients with class III or IV HF (mean LVEF=20%)

LV End-Diastolic DimensionLV End-Diastolic Dimension

Estimated Body Surface AreaEstimated Body Surface Area==

Cardiac Resynchronization Cardiac Resynchronization TherapyTherapy

Cardiac resynchronization therapy (CRT) has Cardiac resynchronization therapy (CRT) has emerged as a promising new treatment for heart emerged as a promising new treatment for heart failure patients with intraventricular conduction failure patients with intraventricular conduction delays or ventricular dysynchronydelays or ventricular dysynchrony

Studies of CRT have demonstrated improvement Studies of CRT have demonstrated improvement in patient symptoms and exercise capacity, in patient symptoms and exercise capacity, quality of life, NYHA class(69% vs. 34% at 6 quality of life, NYHA class(69% vs. 34% at 6 mnths).mnths).

Ventricular DysynchronyVentricular Dysynchrony

Abnormal ventricular conduction resulting Abnormal ventricular conduction resulting in a mechanical delayin a mechanical delayWide QRS (IVCD); typically LBBB Wide QRS (IVCD); typically LBBB

morphologymorphology

Poor systolic functionPoor systolic function

Impaired diastolic functionImpaired diastolic function

Abraham WT, et al. MIRACLE Trial Results; ACC 2001Abraham WT, et al. MIRACLE Trial Results; ACC 2001

ConclusionsConclusions

In NYHA Class III and IV systolic heart In NYHA Class III and IV systolic heart failure patients with intraventricular failure patients with intraventricular conduction delays, CRTconduction delays, CRT is safe and well toleratedis safe and well tolerated improves Quality of Life, functional class, and improves Quality of Life, functional class, and

exercise capacityexercise capacity improves cardiac structure and functionimproves cardiac structure and function improves heart failure composite responseimproves heart failure composite response

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