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

2. Signs and Symptoms 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 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 months18 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 Causes of ReadmissionFrequency (%) Arrythmias8-28 Infections16-23 Poor compliance15-32 Angina14-33 Iatrogenic factors10 Inadequate drug therapy17 Inadequate discharge/follow up35 Failed social support system21 Erhardt and Cline 1998 (Lancet) Over 50% preventable

9. Signs and Symptoms SymptomsSignsInvestigations SOATachycardiaChest X-ray SOBOEIncreased JVPEchocardiogram FatigueOedemaAmbulatory ECG OrthopnoeaRalesExercise treadmill PND (Paroxysmal nocturnal dyspnoea) HepatomegalyCardiac catheter NocturiaAscites AnorexiaCardiomegaly Weight loss

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

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

13. cardiac output cardiac workload Renal blood flow RAS angiotensin aldosterone Na + and H 2 O retention preloadafterload arterio- constriction remodelling veno- constriction Neurohormonal model of Heart Failure – renin-angiotensin-aldosterone Remember Starlings Law

14. cardiac output cardiac workload Renal blood flow RAS angiotensin naturetic peptides aldosterone Na + and H 2 O retention preloadafterload arterio- constriction nor- epinephrine aortic blood flow SNS veno- constriction B-blockers ACE-I NEP-I spironolactone diuretics nitrates hydralazine digoxin Treatment of Heart Failure Remember Survival = drug treatment

15. loops most effective symptomatic relief Na + retention H 2 O loss preload ( ventricle filling pressure) afterload (arterial dilatation) Side effects dehydration hypotension hypokalaemia hypomagnesaemia hypouricaemia and gout non-compliance issues Role of Diuretics

16. Role of ACE-inhibitors 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%)

17. Circulating Renin-Angiotensin System angiotensinogen renin Ang I Ang II ACEACE AT 1 /AT 2 receptors

18. ACEACE Ang (1-5) angiotensinogen renin Ang I Ang II ACE AT 1 AT 2 AT x Ang (1-7) NEPNEP Potential Role of Angiotensin (1-7) pressor trophic antinatriuretic depressor antitrophic natriuretic depressor antitrophic natriuretic

19. angiotensinogen renin Ang I Ang II ACE AT 1 AT 2 AT x Ang (1-7) NEPNEP ACEACE Ang (1-5) + – pressor trophic antinatriuretic depressor antitrophic natriuretic depressor antitrophic natriuretic ACE inhibitor ACE inhibitor Potential Role of Angiotensin (1-7)

20. icatibant bradykinin Ang II Renin-Angiotensin/Kallikrein-Kinin Systems kininogen kallikrein inactive peptides kininase II angiotensinogen renin Ang I ACE B 2 AT 1 AT 2 pressor trophic antinatriuretic depressor antitrophic natriuretic depressor antitrophic cardioprotective NO + – ACE inhibitor B 2 receptor knock-out

21. Landmark trials with ACE inhibitors in HF

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

23. Role of Beta blockers 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

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

25. Role of Digoxin 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

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

27. Adjunct Therapy Digoxin in SRDigoxin 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 AnticoagulationAnticoagulation – 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 hydralazine Benefit vs. placebo; inferior to enalapril (mortality) Davies et al. BMJ 2000;320:428-431 Gibbs et al. BMJ 2000;320:495-498 However: 4-year mortality remains ~ 40% 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 failure Pharmaceutical 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??