1. Optimizing Treatment Of Heart Failure for individual patients By Prof. Mansoor Ahmad FRCP Consultant Cardiologist

2. Introduction A clinical syndrome characterized by progressive weakening of the heart as a pump, causing complex changes in processes at systemic, organ and cellular levels, finally leading to premature myocardial cell death. This leads to salt and water retention with classical symptoms and physical signs.

3. Heart failure Prevalence of symptomatic HF 0.4-2.0%, 6-10% in people over 65 years Disease of the elderly (mean age > 70 years) Prevalence is rising Bad prognosis: 5-year survival rate < 50% Mortality (even if age adjusted) is increasing Laszlo L. Tornoci, Inst. Pathophysiology, Semmelweis University

4. Prognosis Annual mortality rate depends on patients symptoms and LV function 5% in patients with mild symptoms and mild ↓ in LV function 30% to 50% in patient with advances LV dysfunction and severe symptoms 40% – 50% of death is due to SCD

5. Causes of heart failure Underlying (true) causes Precipitating causes (which make the clinical condition worse, ‘decompensate’ the patient)

6. Underlying causes Ischemic heart disease Hypertension Valvular heart disease Cardiomyopathies Other

7. Precipitating causes 1. Increased workload Increased cardiac output –metabolic need (fever, infection, hyperthyroidism) –volume overload (renal failure, high sodium intake) Pressure overload –high BP –pulmonary embolism

8. Precipitating causes 2. Same workload, but weaker heart Cardiac ischemia Decreased efficiency (arrhythmias) Drug effect Endocarditis, myocarditis

9. Precipitating causes 3 Drugs Non Steroidal Anti Inflammatory Drugs Steroids IV fluids Hydralazine Beta blockers Angioedema

10. Summary of drug therapy drug control fluid retention alleviate symptom s prolong survival diuretic+++? ACE inhibitor ++++  -blocker *  (0)  (+) ++ digitalis+++0 * : long term effects are in parentheses

11. Heart failure Treatment is evidence based eg. CONSENSUS 1987 (ACEI) CHARM 2004 (ARB) MERIT HF and COPERNICUS (beta blocker)

12. MERIT-HF and COPERNICUS: Severe Heart Failure Number of Patients to Treat 1 Year in Order to Save One Life  MERIT-HF: 13  COPERNICUS: 15

13. COPERNICUS Inclusion Criteria Defining Heart Failure EF <0.25 within 6 months prior to randomization Symptoms of dyspnea and/or fatigue at rest or on minimal exertion for at least 2 months No pulmonary rales and no ascites at randomization No or only trace (minimal) oedema of the peripheral limbs at randomization (patients with mild oedema may be enrolled if the oedema is due to a venous disorder)

14. Heart failure? Most of the studies use highly selected patients. On an average 12 to 20% of patients are selected out of total screened. Where do the rest of the patients fit??

15. Intolerance to drugs Approximately 15% withdrawal rate for  blocker.

16. MERIT-HF Severe Heart Failure (NYHA III/IV and EF<0.25) All cause Adverse events Wosening CHF p=0.027 p=0.012 p=0.018 No. of withdraw als 86/62 66/42 34/18 Goldstein S et al, JACC 2001;38:932-8

17. MERIT-HF and COPERNICUS: Severe Heart Failure Yearly Withdrawal Rate of Study Medicine Placebo Meto Δp-value CR/XL Placebo Meto Δp-value CR/XL MERIT-HF1 21.7 % 15.5% -31%0.027 COPERNICUS18.5%14.8% -23%0.02 COPERNICUS18.5%14.8% -23%0.02 Goldstein S et al, JACC 2001;38:932-8 Packer et al, NEJM 2001;344:1651-8

18. Heart failure A variety of patients are seen in day to day practice who will not fit completely for the prescribed GUIDELINES.

19. Blood Pressure levels Patients with low Blood Pressure levels tend to tolerate ACE inhibitor, Angiotensin Receptor Blocker and  blocker less well.

20. MERIT-HF Severe Heart Failure (NYHA III/IV and EF<0.25) Baseline Blood Pressure and Heart Rate Variable Placebo Meto CR/XL n=396n=399 Systolic blood pressure 124125 Diastolic blood pressure 7777 Heart rate 8585 Goldstein S et al, JACC 2001;38:932-8

21. MERIT-HF and COPERNICUS: Severe Heart Failure Baseline Blood Pressure and Heart Rate MERIT-HF1COPERNICUS Variable Placebo Meto CR/XL Placebo Carvedilol n=396n=399 n=1133n=1156 SBP124125 123123 DBP7777 7676 HR8585 8080

22. Chronic Obstructive Airway Disease  blocker

23. Chronic kidney disease Caution with ACE inhibitor and Angiotensin Receptor Blocker. BP control

24. Hyperkalemia Hyperkalemia is the commonest reason for temporary pacing. ACE inhibitor Angiotensin Receptor Blocker Spiranolactone Possibly  blocker.

25. Heart failure Maintain symptomatic control Control fluid retension Use diuretics Serum potassium.

26. Heart failure Add ACE inhibitors/ Angiotensin Receptor blocker early Build up the dose over weeks if blood pressure is low Watch out for cough (upto 20%) Serum potassium Serum creatinine

27. Heart failure Add beta blocker after the fluid overload is controlled Build up the dose slowly Watch out for brochospasm, worsening failure??

28. Heart failure Use digoxin appropriately and cautiously Main indication is Fast Atrial Fibrillation with failure Serum potassium Toxicity

29. DIAL: Randomized Trial of Telephonic Intervention in Chronic Heart Failure

31. DIAL: primary endpoint: all-cause mortality/heart failure hospitalizations

32. DIAL: heart failure hospitalization

33. Summary Tailor treatment to individual needs of thepatients Dosage to tolerability levels Support care as much as possible Advise on possible precipitating factors eg. Flu vaccination in autumn for COAD patients

34. Summary Treat cause whenever possible eg. Revascularization, Valve replacement. Control arrythmias Close watch on patients even if they are well, as Sudden Cardiac Death is common in all CRT and ICD in appropriate cases (both clinical and financial) Transplant Artificial heart