The Treatment of Advanced Heart Failure

1. The Treatment of Advanced Heart Failure Shiva Roy FRACP POWH Nov 2000

2. 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

3. 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

4. 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 Chronic CCF: Evolution of stages Normal NYHA Class

5. 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

6. Determinants of Cardiac Output CONTRACTILITY AFTERLOAD PRELOAD STROKE VOLUME HEART RATE • Synergy of LV contraction • Valvular competence CARDIAC OUTPUT

7. Pharmacological Therapy Drug Class NYHA Mortality Symptoms ACE-I 1 - 4 Diuretics 2 - 4 Digoxin 2 - 4 ß-blockers 2 - 3 ( ) Spironolactone 3 - 4 Amlodipine 2 - 4 A2 receptor blockers 2 - 4 ? ? (if ACE-Inhibitor cough)

8. 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

9. 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.

10. 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.

11. 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…

12. 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

13. 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 Hypertrophic cardiomyopathy Ischaemia Infiltration

14. 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

15. 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.

16. Surgery for Heart Failure Conventional revascularisation valve replacement or repair transplantation mechanical ‘bridge’ to transplant cardiomyoplasty LV reduction surgery permanent mechanical heart xenotransplantation Investigational

17. 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

18. Heart Transplantation 1982 - 1999 Actuarial Survival Years post Heart Transplant ISHLTx Reg 2000

19. Australian Transplants Number Heart Transplantation Disadvantages: • Donor shortage • Long waiting times • 10-20% mortality on waiting list • Risks of immuno-suppression • Risk of rejection: acute & chronic Year

20. Novacor out of hospital Thoratec on the ward Evolution in VAD Support Thoratec in Intensive Care

21. Case 1 • 40 yr old female lawyer, N Coast • 30 cigarettes daily, Hypertension • Severe chest pain, nausea, diaphoresis • Refused thrombolysis • Medical therapy

26. 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

30. Case 3 • 19 yr old indigenous Australian • 22 wks pregnant • Intermittent palpitations • Increasing dyspnoea and peripheral oedema

32. Case 4 • 70 yr old surgeon • Sudden dyspnoea after driving off 1st tee • Previously well with no CV history • Loud apical PSM on auscultation with pulmonary oedema

35. Case 5 • 24 yr old Chinese basketballer • ?Deteriorating physical fitness

39. Case 6 • 43 yr old radio presenter • ESRF secondary to wegeners granulomatosus, x3/wk HD • Hypertensive • Inceasingly dyspnoeic

43. ß-blockers ACE-Inhibitors Angio-II blockers digoxin Spironolactone diuretics Exercise CPAP High risk conventional surgery Bi-ventricular pacing? Myoplasty? LVADs Transplantation Left Ventricular reduction surgery? Total artificial heart? Xenografts? Tolerance? Heart Failure 2000: Therapeutic Options Medical Therapy Surgical Therapy