Aktuelle Therapie der Herzinsuffizienz München, 17. Oktober Christian Stumpf Medizinische Klinik 2 (Kardiologie und Angiologie)

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1 Aktuelle Therapie der Herzinsuffizienz München, 17. Oktober 2014 Christian Stumpf Medizinische Klinik 2 (Kardiologie und Angiologie)

2 Todesursachen in Deutschland

3 HERZINSUFFIZIENZ Epidemiologie Häufigste internistische Aufnahmegrund mehr als 10 Mio Menschen in Europa in Deutschland etwa 1,3 Mio Prävalenz (altersabhängig): 1% a 2-5% a 10% >75 a

4 Todesursachen in Deutschland KHK Herzinfarkt Herzinsuffizienz Schlaganfall Lungen - Ca Diabetes Dickdarm - Ca Leber - Zirrhose Mamma - Ca HIV / AIDS Todesfälle/ Einwohner Statistisches Bundesamt 2011

5 HERZINSUFFIZIENZ Ätiologie KHK Dilatative Kardiomyopathie Hypertonie Herzklappenerkrankungen sonstige

6 HERZINSUFFIZIENZ Prognose nach Diagnosestellung 100 Überleben % Malignes Melanom Urothel-CA 40 Prostata-CA Colon-CA 20 Herzinsuffizienz 0 Bronchial-CA Cowie et al., Heart 2000 Follow-up [Monate]

7 Therapie der Herzinsuffizienz

8 Herzinsuffizienz Therapie 1922 Die Krankheiten des Herzens und der Gefäße Hochhaus/Liebermeister Springer, Berlin, 1922

9 Herzinsuffizienz Therapie 1922 Die Krankheiten des Herzens und der Gefäße Hochhaus/Liebermeister Springer, Berlin, 1922

10 Herzinsuffizienz Therapie 2014

11 HERZINSUFFIZIENZ Bausteine der Therapie Ursachenbehandlung Medikamente Device Therapie

12 Diuretika bei Stauungszeichen + ACE-Hemmer (oder AT1-Antag. falls Unverträglichkeit) Betablocker immer noch NYHA II-IV? Ja Nein Aldosteronantagonist Keine weitere Therapie

13 EMPHASIS-HF

14 NYHA II, EF < 35%, n = 2737

15 Aldosteronantagonist immer noch NYHA II-IV? Ja Nein EF<35%? Ja Nein Sinusrhythmus + HF >70/min? Ja Nein Ivabradin Keine weitere Therapie

16 Lancet 2010, 376:

17 Lancet 2010, 376: Prognoseverbesserung bei Herzinsuffizienz? Patienten mit: 1. Herzinsuffizienz NYHA II - IV 2. LV-Dysfunktion 35% 3. Herzfrequenz > 70/Minute 4. KrHs wg. Verschlechterung Einfluss auf Mortalität und Morbidität?

18 Primärer kombinierter Endpunkt Ivabradin n=793 (14.5% pro Jahr) Placebo n=937 (17.7% pro Jahr) Kumulative 40 Häufigkeit (%) 30 Ivabradin Placebo HR = 0.82 p < % 20 NNT=26 (1 Jahr) Effekte nach Monate 3 Monaten sichtbar Lancet 2010; 376:

19 Ivabradin immer noch NYHA II-IV und EF <35%? Ja Nein QRS-Dauer >120 ms? Ja Nein CRT-D ICD Keine weitere Therapie

20 HERZINSUFFIZIENZ Bausteine der Therapie Ursachenbehandlung Medikamente Device Therapie

21

22 2013 ESC Guideline on cardiac pacing and cardiac resynchronization therapy Magnitude of benefit and Recommendations Clinical factors influencing the likelihood of respond to CRT Recommendations Class Level Highest (responders) Lowest (non-responders) Wider QRS, LBBB, females, nonischemic cardiomyopathy Males, ischemic cardiomyopathy Narrower QRS, non-lbbb 1) LBBB with QRS duration > 150 ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d I A 2) LBBB with QRS duration ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 3) Non-LBBB with QRS duration >150 ms. CRT should be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 4) Non-LBBB with QRS duration ms. CRT may be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III IIb B and ambulatory IV despite adequate medical treatment. d I IIa B B 5) CRT in patients with chronic HF with QRS duration <120 ms is not recommended. III B /13

23 2013 ESC Guideline on cardiac pacing and cardiac resynchronization therapy Magnitude of benefit and Recommendations Clinical factors influencing the likelihood of respond to CRT Recommendations Class Level Highest (responders) Lowest (non-responders) Wider QRS, LBBB, females, nonischemic cardiomyopathy Males, ischemic cardiomyopathy Narrower QRS, non-lbbb 1) LBBB with QRS duration > 150 ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d I A 2) LBBB with QRS duration ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 3) Non-LBBB with QRS duration >150 ms. CRT should be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 4) Non-LBBB with QRS duration ms. CRT may be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III IIb B and ambulatory IV despite adequate medical treatment. d I IIa B B 5) CRT in patients with chronic HF with QRS duration <120 ms is not recommended. III B /13

24 2013 ESC Guideline on cardiac pacing and cardiac resynchronization therapy Magnitude of benefit and Recommendations Clinical factors influencing the likelihood of respond to CRT Recommendations Class Level Highest (responders) Lowest (non-responders) Wider QRS, LBBB, females, nonischemic cardiomyopathy Males, ischemic cardiomyopathy Narrower QRS, non-lbbb 1) LBBB with QRS duration > 150 ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d I A 2) LBBB with QRS duration ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 3) Non-LBBB with QRS duration >150 ms. CRT should be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 4) Non-LBBB with QRS duration ms. CRT may be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III IIb B and ambulatory IV despite adequate medical treatment. d I IIa B B 5) CRT in patients with chronic HF with QRS duration <120 ms is not recommended. III B /13

25 2013 ESC Guideline on cardiac pacing and cardiac resynchronization therapy Magnitude of benefit and Recommendations Clinical factors influencing the likelihood of respond to CRT Recommendations Class Level Highest (responders) Lowest (non-responders) Wider QRS, LBBB, females, nonischemic cardiomyopathy Males, ischemic cardiomyopathy Narrower QRS, non-lbbb 1) LBBB with QRS duration > 150 ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d I A 2) LBBB with QRS duration ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 3) Non-LBBB with QRS duration >150 ms. CRT should be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 4) Non-LBBB with QRS duration ms. CRT may be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III IIb B and ambulatory IV despite adequate medical treatment. d I IIa B B 5) CRT in patients with chronic HF with QRS duration <120 ms is not recommended. III B /13

26 2013 ESC Guideline on cardiac pacing and cardiac resynchronization therapy Magnitude of benefit and Recommendations Clinical factors influencing the likelihood of respond to CRT Recommendations Class Level Highest (responders) Lowest (non-responders) Wider QRS, LBBB, females, nonischemic cardiomyopathy Males, ischemic cardiomyopathy Narrower QRS, non-lbbb 1) LBBB with QRS duration > 150 ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d I A 2) LBBB with QRS duration ms. CRT is recommended in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 3) Non-LBBB with QRS duration >150 ms. CRT should be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment. d 4) Non-LBBB with QRS duration ms. CRT may be considered in chronic HF patients and LVEF 35% who remain in NYHA functional class II, III IIb B and ambulatory IV despite adequate medical treatment. d I IIa B B 5) CRT in patients with chronic HF with QRS duration <120 ms is not recommended. III B /13

27 HERZINSUFFIZIENZ Weitere Therapieoptionen

28 Kardiale Kontraktilitätsmodulation CCM

29 Funktionsprinzip: Stimulation des Myokards in der Refraktärphase (nicht exzitatorische Stimulation) 2 biphasische Impulse (ca. 7V, Dauer 20 ms) Erhöhter Ca-Einstrom aus SER in Cytosol Steigerung der Kontraktilität des Myokards 29

30 Force CCM - Effekt Erhöhung der kardialen Kontraktionskraft CCM Off CCM On Time Verstärkt die Kontraktilät in der Region der Stimulation Effektiv bei gesundem und durch HI geschädigtem Myokard

31 Kardiale Kontraktilitätsmodulation CCM - Konzept CCM Impulse werden während der absoluten Refraktärphase abgegeben und normalisieren die Zellfunktion CCM Impulse sind im EKG sichtbar Normales EKG EKG CCM- Spike

32 FIX-HF 5 (USA): Randomisierte Multizenter-Studie n=428 (NYHA III und NYHA IV; LV-EF < 35%). Med. Therapie (n=215) vs. CCM (n=213) VO2 peak Erhöhung um 0,52±ml/kg/min (p=0,03). Verbesserung der Lebensqualität (MLWHFQ) um 3 Punkte (p=0,03) Verbesserung Lebensqualität, NYHA-Klasse, peak VO2.

33 Indikation symptomatische Herzinsuffizienz NYHA II/III EF < 35% Sinusrhythmus! PQ-Zeit < 400 ms

34 HERZINSUFFIZIENZ Ausblick medikamentöse Therapie

35 Paradigm HF

36 36

37 Paradigm HF - Patient disposition

38 Paradigm HF Primary endpoint Primary end point

39 Paradigm HF Cardiovascular Death

40 Paradigm HF All cause mortality

41

42 HERZINSUFFIZIENZ Bausteine der Therapie Sport? Ursachenbehandlung Medikamente Device Therapie

43 die Zeiten haben sich geändert.. Outline of Treatment of Chronic Congestive Heart Failure 1. Restriction of Physical Activity (A) Discontinue exhausting sports and heavy labor (B) Discontinue full-time work or equivalent activity, introduce rest periods during the day (C) Confine to house (D) Confine to bed-chair ( ) E. Braunwald: Heart Disease, 2nd ed. 1984

44 HERZINSUFFIZIENZ - Körperliche Aktivität

45 HERZINSUFFIZIENZ Körperliche Aktivität - Evidenzen

46 HERZINSUFFIZIENZ Körperliche Aktivität - Evidenzen Leipzig Heart Failure Trial Hambrecht et al., JAMA 2000 Aerobic Interval Training in HF, Wisloff et al., Circulation 2007 HF-Action, O Connor et al., JAMA 2009 Smartex-HF, not yet published

47 Therapie der der Herzinsuffizienz nach Leitlinie Dekompensiert Diuretika (Dosis im Verlauf anpassen) Jeder mit EF ACE-Hemmer/AT1-Antagonist Noch symptomatisch (oder KHK) Betablocker Noch symptomatisch, EF < 35% Aldosteronantagonist HF noch > 70/min (Sinusrhythmus) Ivabradine EF<35% + QRS< 120 ms ICD EF<35% + QRS > 120 ms CRT-D

48 Therapie der der Herzinsuffizienz nach Leitlinie Dekompensiert Diuretika (Dosis im Verlauf anpassen) Jeder mit EF ACE-Hemmer/AT1-Antagonist Noch symptomatisch (oder KHK) Betablocker Noch symptomatisch, EF < 35% Aldosteronantagonist HF noch > 70/min (Sinusrhythmus) Ivabradine EF<35% + QRS< 120 ms ICD EF<35% + QRS > 120 ms CRT-D

49 Vielen Dank für Ihre Aufmerksamkeit