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Transcript
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 •LV dysfunction = CCF •Symptoms may not be proportional to extent of LV dysfunction 3 Symptoms with minor exertion 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 AFTERLOAD PRELOAD STROKE VOLUME •Synergy of LV contraction •Valvular competence HEART RATE CARDIAC OUTPUT Pharmacological Therapy Drug Class ACE-I Diuretics Digoxin ß-blockers Spironolactone Amlodipine A2 receptor blockers (if ACE-Inhibitor cough) NYHA 1-4 2-4 2-4 2-3 3-4 2-4 2-4 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 Hypertension Ischaemia Uncommon causes 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 immunosuppression 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 1st 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 Medical Therapy ACE-Inhibitors Spironolactone Angio-II blockers diuretics High risk conventional surgery Bi-ventricular pacing? Left Ventricular reduction surgery? digoxin Exercise CPAP Myoplasty? ß-blockers Surgical Therapy Transplantation Xenografts? Tolerance? LVADs Total artificial heart?