The Treatment of Advanced The Treatment of Advanced Heart FailureHeart Failure

Shiva Roy FRACP Shiva Roy FRACP

POWH Nov 2000POWH Nov 2000

Heart Failure: where are we now?Heart Failure: where are we now?

CCF is a major health problem» 400,000 new cases / yr in USA » 300,000 Australians affected

Care is expensive» 70% of costs relate to hospitalisation» $1.1 billion/year inpatient costs in Australia » commonest hospital DRG in USA in pts > 65 yrs

High mortality & readmission rates» > 40% readmissions / year after index admission

Heart FailureHeart Failure

DefinitionDefinition

““The situation when the heart is The situation when the heart is incapable of maintaining a cardiac output incapable of maintaining a cardiac output adequate to accommodate metabolic adequate to accommodate metabolic requirements and the venous return”requirements and the venous return”

E. BraunwaldE. Braunwald

Normal

Chronic CCF: Evolution of stagesChronic CCF: Evolution of stages

NYHA Class

AsymptomaticLV dysfunction

1

Symptoms on exercise

2

Symptoms with minor exertion

3

•LV dysfunction = CCF•Symptoms may not be proportional to extent of LV dysfunction

4

Symptoms at rest

Assessment of Heart FailureAssessment of Heart Failure

DiagnosisDiagnosis» symptoms often more useful than signssymptoms often more useful than signs» CXR, ECG helpfulCXR, ECG helpful» echocardiography is essentialechocardiography is essential

Exclusion of treatable causesExclusion of treatable causes» ischaemiaischaemia» valvular lesionsvalvular lesions» uncontrolled HTuncontrolled HT» thyrotoxicosisthyrotoxicosis» arrhythmias arrhythmias » anaemiaanaemia

Determinants of Cardiac OutputDeterminants of Cardiac Output

STROKE VOLUMESTROKE VOLUME

CONTRACTILITYCONTRACTILITY

PRELOADPRELOAD

HEART RATEHEART RATE

CARDIAC OUTPUTCARDIAC OUTPUT

AFTERLOADAFTERLOAD

•Synergy of LV contractionSynergy of LV contraction•Valvular competenceValvular competence

Pharmacological TherapyPharmacological Therapy

Drug ClassDrug Class NYHA NYHA MortalityMortality SymptomsSymptomsACE-IACE-I 1 - 4 1 - 4

DiureticsDiuretics 2 - 4 2 - 4

DigoxinDigoxin 2 - 4 2 - 4

ß-blockersß-blockers 2 - 3 2 - 3 ( ) ( )

SpironolactoneSpironolactone 3 - 4 3 - 4

AmlodipineAmlodipine 2 - 4 2 - 4

A2 receptor blockers 2 - 4A2 receptor blockers 2 - 4 ? ? ? ? (if ACE-Inhibitor cough)(if ACE-Inhibitor cough)

ACE InhibitorsACE Inhibitors

Alters balance between vasoconstrictive, salt Alters balance between vasoconstrictive, salt retaining, hypertrophic properties of angiotensin II retaining, hypertrophic properties of angiotensin II and, the vasodilatory and natriuretic properties of and, the vasodilatory and natriuretic properties of bradykinin.bradykinin.

Morbidity and mortality data from large trials in Morbidity and mortality data from large trials in spectrum of LVF make ACE inhibitors mandatory spectrum of LVF make ACE inhibitors mandatory (SAVE, SOLVD, CONCENSUS, AIRE…)(SAVE, SOLVD, CONCENSUS, AIRE…)

? High dose – ATLAS study? High dose – ATLAS study HOPE – reduced Cardiac death, CVA, & non fatal MI HOPE – reduced Cardiac death, CVA, & non fatal MI

in ramipril treated pts with documented vascular in ramipril treated pts with documented vascular disease but no heart failuredisease but no heart failure

Aldosterone antagonistsAldosterone antagonists

Aldosterone causes Na retention, K/Mg loss, Aldosterone causes Na retention, K/Mg loss, myocardial fibrosis, baroreceptor dysfunction, myocardial fibrosis, baroreceptor dysfunction, catechol augmentation and ventricular catechol augmentation and ventricular arrhythmogenicity.arrhythmogenicity.

RALES demonstrated 30% reduction in all RALES demonstrated 30% reduction in all cause mortality, and in hospitalisation in cause mortality, and in hospitalisation in spironolactone (md 26mg) treated pts with spironolactone (md 26mg) treated pts with NYHA III & IV heart failureNYHA III & IV heart failure

Well tolerated with conventional therapy.Well tolerated with conventional therapy.

Angiotensin receptor antagonistsAngiotensin receptor antagonists

High levels of Angiotensin II predict poor outcome, and High levels of Angiotensin II predict poor outcome, and ACE inhibition of bradykinin metabolism may induce ACE inhibition of bradykinin metabolism may induce cough. cough.

Unexpected benefit of Losartan in ELITE, not confirmed Unexpected benefit of Losartan in ELITE, not confirmed in ELITE IIin ELITE II

Adverse outcome with Candesartan v Enalapril in Adverse outcome with Candesartan v Enalapril in RESOLVDRESOLVD

Val- HeFT (class II and III)standard triple Rx v Val- HeFT (class II and III)standard triple Rx v combination Rx, and VALIANT – valsartan v Captopril combination Rx, and VALIANT – valsartan v Captopril V combination post MIV combination post MI

Current role of AII R blockers is in ACE I intolerant pts Current role of AII R blockers is in ACE I intolerant pts and as adjunct to conventional therapy.and as adjunct to conventional therapy.

Sympathetic activation in CCFSympathetic activation in CCF

B Blockers ? Contraindicated B Blockers ? Contraindicated Down regulation of B1 AR’s due to high catechol levels Down regulation of B1 AR’s due to high catechol levels

with failing myocardium.with failing myocardium. US Carvedilol heart failure study 65% decrease US Carvedilol heart failure study 65% decrease

mortality, ANZHF 24% NS reduction in mortality.mortality, ANZHF 24% NS reduction in mortality. COPERNICUS – favourable carvedilol effect in severe COPERNICUS – favourable carvedilol effect in severe

HF.HF. B1 selective blockers Metoprolol (CR) – MERIT-HF B1 selective blockers Metoprolol (CR) – MERIT-HF

3991 pts, FC II-IV, 34% decrease in CV mortality, 41% 3991 pts, FC II-IV, 34% decrease in CV mortality, 41% decrease in SCD with similar results for Bisoprolol – decrease in SCD with similar results for Bisoprolol – CIBIS II.CIBIS II.

COMET – Carvedilol or Metoprolol European Trial…COMET – Carvedilol or Metoprolol European Trial…

Therapy of Heart FailureTherapy of Heart Failure

» pharmacological management» treatment of arrhythmias: esp AF» lifestyle: Na+ & fluid restriction, weight

loss, cessation of smoking, alcohol» exercise » management of co-morbidities:

depression, sleep apnoea» vaccination against respiratory pathogens

Comprehensive care is essential

Diastolic Heart FailureDiastolic Heart Failure

Stiffening of the ventricle Stiffening of the ventricle » Poor filling, need for higher than normal filling pressures Poor filling, need for higher than normal filling pressures » Small fluid shifts often poorly tolerated Small fluid shifts often poorly tolerated » Difficult balance between pulmonary congestion and Difficult balance between pulmonary congestion and

systemic hypotensionsystemic hypotension

Often accompanies systolic heart failureOften accompanies systolic heart failure Isolated diastolic failure:Isolated diastolic failure:

Common causes Uncommon causes

Hypertension Hypertension Hypertrophic cardiomyopathyHypertrophic cardiomyopathy

Ischaemia Ischaemia InfiltrationInfiltration

Management is difficult!

Isolated Diastolic Heart FailureIsolated Diastolic Heart Failure

treat the underlying cause lower the HR, improve relaxation:

ß-blocker or verapamil atrial fibrillation: attempt restoration of

sinus rhythm ACE-inhibitors, spironolactone: may

cause regression of hypertrophy cautious use of diuretics digoxin unhelpful

Biventricular PacingBiventricular Pacing

DCM with IVCD is associated with significant DCM with IVCD is associated with significant interventricular dyssynchronyinterventricular dyssynchrony

BV pacing may promote a coordinated BV pacing may promote a coordinated ventricular pattern of contraction.ventricular pattern of contraction.

Symptomatic benefit demonstrated to date.Symptomatic benefit demonstrated to date.

Surgery for Heart FailureSurgery for Heart Failure

ConventionalConventionalrevascularisationrevascularisationvalve replacement or repairvalve replacement or repairtransplantationtransplantationmechanical ‘bridge’ to transplantmechanical ‘bridge’ to transplantcardiomyoplastycardiomyoplastyLV reduction surgeryLV reduction surgerypermanent mechanical heartpermanent mechanical heartxenotransplantationxenotransplantation

InvestigationalInvestigational

Heart TransplantationHeart Transplantation

Indications•End stage heart failure, NYHA class 3-4, no further therapeutic options•Poor LV function alone is not an indication in the absence of significant symptoms

Contraindications•Severe systemic disease limiting survival•Active infection•Irreversible pulmonary hypertension•Adverse psycho-social factors

Heart Transplantation 1982 - 1999Heart Transplantation 1982 - 1999

Years post Heart Transplant

Actuarial SurvivalActuarial Survival

ISHLTx Reg 2000

Heart TransplantationHeart Transplantation

Disadvantages:Disadvantages: Donor shortageDonor shortage Long waiting timesLong waiting times 10-20% mortality 10-20% mortality

on waiting list on waiting list Risks of immuno-Risks of immuno-

suppressionsuppression Risk of rejection: Risk of rejection:

acute & chronicacute & chronic0

20

40

60

80

100

120

'84 '85 '86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99

Nu

mb

er

Australian Transplants

Year

Thoratec in Intensive Care

Evolution in VAD SupportEvolution in VAD Support

Novacor out ofhospital

Thoratec on the ward

Case 1Case 1

40 yr old female lawyer, N Coast40 yr old female lawyer, N Coast 30 cigarettes daily, Hypertension30 cigarettes daily, Hypertension Severe chest pain, nausea, diaphoresisSevere chest pain, nausea, diaphoresis Refused thrombolysisRefused thrombolysis Medical therapyMedical therapy

Case 2Case 2

77 yr old female77 yr old female Independent with medical therapy for Independent with medical therapy for

ischemic cardiomyopathy and hypertensionischemic cardiomyopathy and hypertension Known moderate LV impairment (EF ~40%)Known moderate LV impairment (EF ~40%) Sudden onset of increasing breathlessnessSudden onset of increasing breathlessness No chest pain No chest pain

Case 3Case 3

19 yr old indigenous Australian19 yr old indigenous Australian 22 wks pregnant22 wks pregnant Intermittent palpitationsIntermittent palpitations Increasing dyspnoea and peripheral oedemaIncreasing dyspnoea and peripheral oedema

Case 4Case 4

70 yr old surgeon70 yr old surgeon Sudden dyspnoea after driving off 1Sudden dyspnoea after driving off 1stst tee tee Previously well with no CV historyPreviously well with no CV history Loud apical PSM on auscultation with Loud apical PSM on auscultation with

pulmonary oedemapulmonary oedema

Case 5Case 5

24 yr old Chinese basketballer24 yr old Chinese basketballer ?Deteriorating physical fitness?Deteriorating physical fitness

Case 6Case 6

43 yr old radio presenter43 yr old radio presenter ESRF secondary to wegeners ESRF secondary to wegeners

granulomatosus, x3/wk HDgranulomatosus, x3/wk HD HypertensiveHypertensive Inceasingly dyspnoeicInceasingly dyspnoeic

Heart Failure 2000: Therapeutic OptionsHeart Failure 2000: Therapeutic Options

High risk conventional

surgery

TransplantationLVADs

Total artificial heart?

Xenografts?

Tolerance?

Bi-ventricular pacing?

Myoplasty?

Left Ventricular reduction surgery?

Exercise

ß-blockersACE-Inhibitors

Angio-II blockers digoxindiureticsSpironolactone

CPAP

Medical Therapy

Surgical Therapy