Congestive Heart Failure

1. Congestive Heart Failure Dr Ian Coombes Adopted from Duncan McRobbie Principal Clinical Pharmacist (with permission)

2. fatigue exertional dyspnoea orthopnoea PND cardiomegaly pitting oedema crackles raised JVP NYHA I - no limitation of physical activity NYHA II- slight limitation NYHA III - marked limitation NYHA IV - inability to carry out physical activity Signs and Symptoms NYHA Classification

3. acute MI hypertension toxins (alcohol, cytotoxics) viruses/bacteria valve disease cardiomyopathies Causes

4. Prevalence • 1-2% population • 3-5% of those >65 years of age • 10% of those >80 years • 50% patients die within 2 years of diagnosis • 65% of patients with severe CHF die within 1 yr

5. Survival After Initial Diagnosis of HF 100% 50% 0% 3 months 18 months

6. Hospitalisations • 74,500 hospital admissions in 2000/2001 • Length of stay > 13 days (3x average LOS) • 1,000,000 in-patient days • Admission rates projected to increase by >50% over the next 25 years • Readmission rates as high as 50% over 3 months

7. Readmission - causes Over 50% preventable Erhardt and Cline 1998 (Lancet)

9. Signs and Symptoms

10. Classifying Heart Failure – the New York Heart Association method • NYHA I No symptoms with ordinary physical activity (walking and climbing stairs) • NYHA II (mild) Slight limitation of activity with dyspnoea on moderate to severe activity (climbing stairs or walking uphill) • NYHA III (moderate) Marked limitation of activity. Less than ordinary activity causes dyspnoea (restricting walking distance and limiting climbing to one flight of stairs) • NYHA IV (severe) Severe disability, dyspnoea at rest (unable to carry out physical activity without discomfort)

11. Rules of HF Remember symptoms haemodynamics symptoms survival Remember CO=SVxHR BP=TPRxCO Remember Starling’s Law: preload = force of contraction Lapace’s Law: large heart = inefficient

12. Neurohormonal model of Heart Failure – Sympathetic Response afterload cardiac workload arterio- constriction nor- epinephrine cardiac output aortic blood flow SNS Remember CO = SV x HR

13. Neurohormonal model of Heart Failure – renin-angiotensin-aldosterone afterload preload cardiac workload Na+ and H2O retention arterio- constriction Remember Starlings Law aldosterone remodelling cardiac output Renal blood flow veno- constriction RAS angiotensin

14. Treatment of Heart Failure Remember Survival = drug treatment afterload preload hydralazine cardiac workload diuretics Na+ and H2O retention arterio- constriction digoxin spironolactone nor- epinephrine aldosterone cardiac output nitrates aortic blood flow Renal blood flow veno- constriction B-blockers RAS SNS ACE-I angiotensin naturetic peptides NEP-I

15. loops most effective symptomatic relief Na+ retention H2O loss preload ( ventricle filling pressure) afterload (arterial dilatation) Side effects dehydration hypotension hypokalaemia hypomagnesaemia hypouricaemia and gout non-compliance issues Role of Diuretics

16. improves mortality (CONSENSUS) better than vasodilator therapy (VeHFT I and II) large well conducted trials preload (inhibits effect) afterload (inhibits vasoconstriction) Side effects hypotension (6%) hyperkalaemia (6%) cough (40%) dizziness (50%) raised serum creatinine (0.2%) Role of ACE-inhibitors

17. Circulating Renin-Angiotensin System angiotensinogen renin A C E Ang II Ang I AT1/AT2 receptors

18. A C E Ang (1-5) Potential Role of Angiotensin (1-7) angiotensinogen renin N E P Ang (1-7) Ang I ACE Ang II AT1 AT2 ATx pressor trophic antinatriuretic depressor antitrophic natriuretic depressor antitrophic natriuretic

19. + – Potential Role of Angiotensin (1-7) angiotensinogen ACE inhibitor renin A C E N E P Ang (1-7) Ang (1-5) Ang I ACE inhibitor ACE Ang II AT1 AT2 ATx pressor trophic antinatriuretic depressor antitrophic natriuretic depressor antitrophic natriuretic

20. Renin-Angiotensin/Kallikrein-Kinin Systems kininogen angiotensinogen kallikrein renin bradykinin + Ang I ACE inhibitor kininase II ACE – Ang II inactive peptides icatibant B2 receptor knock-out B2 AT1 AT2 depressor antitrophic cardioprotective pressor trophic antinatriuretic depressor antitrophic natriuretic NO

21. Landmark trials with ACE inhibitors in HF

22. improves mortality (ELITE I and II / CHARM) added into conventional therapy (ValHeft / CHARM) Less s/es Role of ARBs

23. improves mortality (CIBIS 2) added into conventional therapy attenuates sympathetic drive (outweighs -ve ionotropic effect) not all beta-blockers are equivalent (bisoprolol and carvedilol best supported by evidence) Side effects hypotension bradycardia peripheral vasoconstriction impotence bronchospasm Role of Beta blockers

24. preload (venodilators - nitrates) afterload (arterial dilators - prazosin) large trials show good benefit but lots of side effects Side effects hypotension headache tachycardia SLE (hydralazine) Role of vasodilator therapy

25. used in initial trials myocardial contractility lost favour because of toxicity renally cleared - dependent on age, weight & RF Side effects anorexia N,V,D abdominal pain visual disturbances drowsiness arrythmias heart block Role of Digoxin

26. improves mortality (RALES) added into conventional therapy attenuates aldosterone effect only small doses required Side effects hyperkalaemia gi disturbances impotence gynocomastia rash Role of spironolactone

27. Adjunct Therapy • Digoxin in SR • DIG trial : no mortality benefit but reduction in hospitalisations and improved symptoms • useful in symptomatic patients where other drug therapy is optimised • should not be withdrawn from pts with HF • Anticoagulation • if prolonged bed rest : prophylactic heparin • if LV dilatation / thrombus : chronic warfarin therapy

28. Mortality remains high • ACEi Risk reduction 35%(mortality and hospitalizations) •  Blockers Risk reduction 38%(mortality and hospitalizations) • Oral nitrates and hydralazineBenefit vs. placebo; inferior to enalapril (mortality) However: 4-year mortality remains ~40% Davies et al. BMJ 2000;320:428-431 Gibbs et al. BMJ 2000;320:495-498 Davies et al. BMJ 2000;320:428-431 Gibbs et al. BMJ 2000;320:495-498

29. Role of other treatments • ?? Ca++ channel antagonists - -ve ionotropic, amlodipine appears safe • ?? other antiarrythmics - • dobutamine - increases CO, but palliative • Levosimendan- severe CHF • naturetic peptide inhibitors / recombinant naturetic peptides- omapatrilat / neseritide • Biventricular pacing - severe CHF high cost • transplantation - 85% survival @ 5yrs

30. Congestive cardiac failurePharmaceutical Care Plan Need for Drug : Diagnosis of CHF Selection of Specific Drug: Symptom control - diuretics Decrease mortality; ACE, B-blockers Co-modibdity: anticoagulation Patient factors Selection of Regimen: Loading doses, maintenance dose Drug factors Provision of Drug: Timely, accurate Administration of Drug: Timing, food Monitor Effectiveness: Symptoms, pulse,cholesterol, side effects Counsel / Educate: Expected effects, side effects Risks vs benefits Evaluate Effectiveness: Beneficial effects > detrimental effects??