The Treatment of Advanced Heart Failure

Shiva Roy FRACP POWH Nov 2000

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 Failure

Definition

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

Chronic CCF: Evolution of stages

Normal

1

Asymptomatic LV dysfunction

2

Symptoms on exercise

3

Symptoms with minor exertion •

LV dysfunction = CCF

•

Symptoms may not be proportional to extent of LV dysfunction

4

Symptoms at rest

Assessment of Heart Failure

 Diagnosis » » » symptoms often more useful than signs CXR, ECG helpful echocardiography is essential  Exclusion of treatable causes » » » » » » ischaemia valvular lesions uncontrolled HT thyrotoxicosis arrhythmias anaemia

Determinants of Cardiac Output

CONTRACTILITY PRELOAD AFTERLOAD STROKE VOLUME •Synergy of LV contraction •Valvular competence HEART RATE

CARDIAC OUTPUT

Pharmacological Therapy

Drug Class ACE-I NYHA 1 - 4 Diuretics Digoxin ß-blockers 2 - 4 2 - 4 2 - 3 Spironolactone Amlodipine 3 - 4 2 - 4 A2 receptor blockers 2 - 4

(if ACE-Inhibitor cough)

Mortality Symptoms ?

( ) ?

ACE Inhibitors

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

   Morbidity and mortality data from large trials in spectrum of LVF make ACE inhibitors mandatory (SAVE, SOLVD, CONCENSUS, AIRE…) ? High dose – ATLAS study HOPE – reduced Cardiac death, CVA, & non fatal MI in ramipril treated pts with documented vascular disease but no heart failure

Aldosterone antagonists

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

 RALES demonstrated 30% reduction in all cause mortality, and in hospitalisation in spironolactone (md 26mg) treated pts with NYHA III & IV heart failure  Well tolerated with conventional therapy.

Angiotensin receptor antagonists

 High levels of Angiotensin II predict poor outcome, and ACE inhibition of bradykinin metabolism may induce cough.  Unexpected benefit of Losartan in ELITE, not confirmed in ELITE II  Adverse outcome with Candesartan v Enalapril in RESOLVD  Val- HeFT (class II and III)standard triple Rx v combination Rx, and VALIANT – valsartan v Captopril V combination post MI  Current role of AII R blockers is in ACE I intolerant pts and as adjunct to conventional therapy.

Sympathetic activation in CCF

  B Blockers ? Contraindicated Down regulation of B1 AR’s due to high catechol levels with failing myocardium.

    US Carvedilol heart failure study 65% decrease mortality, ANZHF 24% NS reduction in mortality.

COPERNICUS – favourable carvedilol effect in severe HF.

B1 selective blockers Metoprolol (CR) – MERIT-HF 3991 pts, FC II-IV, 34% decrease in CV mortality, 41% decrease in SCD with similar results for Bisoprolol – CIBIS II.

COMET – Carvedilol or Metoprolol European Trial…

Therapy of Heart Failure

Comprehensive

care is essential

» » » 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

Diastolic Heart Failure

 Stiffening of the ventricle » » » Poor filling, need for higher than normal filling pressures Small fluid shifts often poorly tolerated Difficult balance between pulmonary congestion and systemic hypotension  Often accompanies systolic heart failure  Isolated diastolic failure: Common causes Uncommon causes Hypertension Ischaemia Hypertrophic cardiomyopathy Infiltration

Isolated Diastolic Heart Failure

Management is difficult!

 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 Pacing

 DCM with IVCD is associated with significant interventricular dyssynchrony  BV pacing may promote a coordinated ventricular pattern of contraction.

 Symptomatic benefit demonstrated to date.

Surgery for Heart Failure

Conventional revascularisation valve replacement or repair transplantation mechanical ‘bridge’ to transplant cardiomyoplasty LV reduction surgery permanent mechanical heart xenotransplantation Investigational

Heart 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 - 1999

Actuarial Survival

Years post Heart Transplant

ISHLTx Reg 2000

Heart Transplantation

Australian Transplants

120 100 80 60 40 20 0 '84 '85 '86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99

Year Disadvantages:  Donor shortage  Long waiting times  10-20% mortality on waiting list  Risks of immuno suppression  Risk of rejection: acute & chronic

Evolution in VAD Support

Thoratec in Intensive Care Thoratec on the ward Novacor out of hospital

Case 1

 40 yr old female lawyer, N Coast  30 cigarettes daily, Hypertension  Severe chest pain, nausea, diaphoresis  Refused thrombolysis  Medical therapy

Case 2

 77 yr old female  Independent with medical therapy for ischemic cardiomyopathy and hypertension  Known moderate LV impairment (EF ~40%)  Sudden onset of increasing breathlessness  No chest pain

Case 3

 19 yr old indigenous Australian  22 wks pregnant  Intermittent palpitations  Increasing dyspnoea and peripheral oedema

Case 4

 70 yr old surgeon  Sudden dyspnoea after driving off 1 st tee  Previously well with no CV history  Loud apical PSM on auscultation with pulmonary oedema

Case 5

 24 yr old Chinese basketballer  ?Deteriorating physical fitness

Case 6

 43 yr old radio presenter  ESRF secondary to wegeners granulomatosus, x3/wk HD  Hypertensive  Inceasingly dyspnoeic

Heart Failure 2000: Therapeutic Options

CPAP

Medical Therapy

ß-blockers ACE-Inhibitors Spironolactone Angio-II blockers diuretics Exercise digoxin Bi-ventricular pacing?

Myoplasty?

Surgical Therapy

High risk conventional surgery

LVADs

Transplantation Left Ventricular reduction surgery?

Tolerance?

Xenografts?

Total artificial heart?