Heart Failure Update. Michael Fu. Professor, Överläkare

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1 Heart Failure Update Michael Fu Professor, Överläkare

2 Update in Diagnosis Update in Pharmacological Treatment Update in Device Therapy Heart Failure in the Elderly Put Guidelines into Clinical Practice

3 Update in Diagnosis

4 The very essence of cardiovascular medicine is the recognition of early heart failure Sir Thomas Lewis 1933

5 Definition of heart failure Symptom typical of HF + Signs typical of HF + Objective evidence of a structural or functional abnormalty of the heart at rest (cardiomegaly, 3rd heart sound, murmurs, abnormalty on echo, raised natriuretic peptide)

6 BNP Brain Natriuretic Peptide B type Natriuretic Peptide

7

8 BNP/NTpro BNP Ett fönster för hjärtas hemodynamik

9 Skillnad mellan BNP och NTpro BNP BNP NT-proBNP Aminosyror MV Biologiskt aktiv ja nej Halveringstid (min) Analysmetod Bedside Ja Ja Central-Lab Nej Ja Känslighet Ngt mer vid lindrig hjärtsvikt Eliminering Neutral peptidase Njur

10 Så länge BNP resp NTpro BNP analyseras korrekt! BNP Likvärdig NTpro-BNP

11 Evidence

12

13 Dokainish et al: Circulation 2004, 109(20): 2432-

14 Systolisk svikt Diastolisk svikt LVEF BNP NTpro BNP

15 ESC guideline 2008 Clinical examination, ECG, Chest X-ray Natriuretic peptides BNP <100 NTpro BNP <400 BNP NTpro BNP BNP >400 NTpro BNP >2000 CHF unlikely CHF uncertain CHF likely

16 Update in Pharmacological Treatment

17 ESC guideline 2008 Objectives of treatment of chronic heart failure Prognosis Life quality Morbidity Prevention

18 Farmaka vid hjärtsvikt Βeta-adrenerga receptor blokerare (Beta-blokerare) ACE hämmare Aldosteron receptor antagonist Angiotensin receptor blokerare (AT1 blokerare) Digitalis Diuretika Antikoagulation Vasodilaterare Antiarytmika Inotropa Kalcium kanal blokerare Statin ASA

19 Evidence based step by step medications Class II Class III Class IV ß blocker ACE inhibitor ß blocker ACE inhibitor ARB ß blocker ACE inhibitor ARB Spironolacton

20 Symptomatic CHF ACEI+BB Yes Persisting symptoms & sign NO ARB or Aldosterone antagonist Persisting symptoms Yes NO LVEF<35% Yes QRS>120 ms CRT/CRT-D Yes ICD

21 Symptomatic CHF ACEI+BB ACEI intolerance ARB VILKA?

22 Mortality Survival Event-free Survival CV Death or HF Hosp 1.0 Val-HeFT.5 CHARM-Alternative Placebo Valsartan 320mg Placebo Candesartan 32 mg.6.3 Cohn et al: NEJM 2001 VALIANT Valsartan 320 mg 27 mos Captopril 150 mg Granger et al: Lancet 2003 ELITE-2 Losartan 50 mg 42 mos Captopril 150 mg 0 Pfeffer et al. NEJM 2003 Pitt B et al: Lancet mos 23 mos

23 Comparison of Low-Dose Versus High-Dose Losartan Treatment on Morbidity and Mortality in Angiotensin-Converting-Enzyme-Inhibitor- Intolerant Patients with Heart Failure and Reduced Left Ventricular Ejection Fraction: Results of the HEAAL* Study Marvin A. Konstam, James D. Neaton, Kenneth Dickstein, Helmut Drexler, Michel Komajda, Felipe A. Martinez, Gunter A.J. Riegger, Ronald D. Smith, William Malbecq, Soneil Guptha, Philip A. Poole- Wilson for the HEAAL investigators Lancet 2009; 374:

24 % of Patients with First Event Percentage of patients with first event Death or Hospitalization for HF 50 Losartan 50 mg Losartan 150 mg HR 0.90 (0.82, 0.99) Hazard ratio: 0.90, p=0.027 P=0.027 Note! Losartan 150 mg 10 0 Losartan 50 mg Number of patients at risk Losartan 150 mg Years Konstam MA et al, Lancet 2009; 374:

25 ARB Indication no. 1 Vid ACE inhibitor intolerance Candesartan (Atacand) Valsartan (Diovan) Losartan * endast 150 mg

26 Symptomatic CHF ACEI+BB Yes Persisting symptoms & sign NO ARB or Aldosterone antagonist VILKEN?

27 As add-on ARB or Aldosteron antagonist?

28 ARB Indication no. 2 Add-on treatment (on top of ACEI)

29 Behandling med ARB Kandesartan Valsartan Startdos (mg) 4-8 x 1 20 x 2 Måldos (mg) 32 x x 2 Måldos eftersträvas. Dosdubblering varje till varannan vecka. Kontroll av s-kreatinin och s-kalium. 51

30 CHARM Programme

31 CHARM-Added Primary outcome, CV death or CHF hospitalisation % Placebo 538 (42.3%) 483 (37.9%) 30 Candesartan Number at risk 0 HR 0.85 (95% CI ), p=0.011 Adjusted HR 0.85, p= years Candesartan Placebo McMurray et al, Lancet 2003

32 Aldosteron antagonist

33 Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms EMPHASIS-HF* Faiez Zannad, M.D., Ph.D., John J.V. McMurray, M.D., Henry Krum, M.B., PhD., Dirk J. van Veldhuisen, M.D.,Ph.D., Karl Swedberg, M.D., Ph.D, Harry Shi, M.S., John Vincent, M.B., PhD., Stuart J Pocock, Ph.D. and Bertram Pitt, M.D. for the EMPHASIS-HF Study Group ClinicalTrials.gov, NCT * Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure

34 Mineralocorticoid Receptor Antagonists (MRAs) in Heart Failure Survival 30% RR, P < Spironolactone Months HYPOTHESIS: Total Mortality 15% RR, P=0.008 Placebo Months Eplerenone Eplerenone, added to evidence-based therapy, is 10 associated with improved clinical outcomes in patients Placebo with systolic heart failure and mild symptoms RALES (LVSD, CHF severe symptoms) Pitt B, Zannad F, Remme WJ, et al. N Engl J Med EPHESUS (LVSD + HF after MI) Pitt B, Remme W, Zannad F, et al. N Engl J Med. 2003

35 Study Design and Sample Size 25 mg Eplerenone 50 mg qd 25 mg Placebo 50 mg qd Screen Randomization 1 Month 3 Months Follow-up Primary endpoint: CV death or hospitalization for HF Zannad et al N Engl Med 2011;364:11-21

36 Primary Endpoint: Cumulative K-M Rate (%) Primary Endpoint Cardiovascular Death or Hospitalization for HF HR [95% CI] = 0.63 [0.54, 0.74] P < Placebo 356 (25.9) Eplerenone 249 (18.3) RRR; 37% ARR; 7,6% No. at Risk Years from Randomization Placebo Eplerenone *Unadjusted HR 0.66; 0.56, 0.78; p< Zannad et al N Engl Med 2011;364:11

37 All-Cause Mortality: Cumulative K-M Rate (%) Mortality From Any Cause HR [95% CI] = 0.76 [0.62, 0.93] P = Placebo 213 (15.5) Eplerenone 171 (12.5) RRR;24% ARR; 3% No. at Risk Years from Randomization Placebo Eplerenone *Unadjusted HR, 0.78; 0.64, 0.95; p=0.01 Zannad et al N Engl Med 2011;364:11

38 As add-on ARB or Spironolakton? Spironolakton

39 Evidence based step by step medications Class II Class III Class IV ß blocker ACE inhibitor Spironolacton ß blocker ACE inhibitor ARB Spironolacton ß blocker ACE inhibitor ARB Spironolacton

40 Ivabradine

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