Heart Failure Therapies State of the Art 2017

Transcription

1 Heart Failure Therapies State of the Art 2017 Andrew J. Sauer, MD Assistant Professor Director, Center for Heart Failure Medical Director, Heart Transplantation UNOS Primary Transplant Physician

2 Disclosures Novartis: Speaker Honorarium Medtronic: Speaker/Consultant Honorarium 10/23/17 2

3 Learning Objectives Understand the heart failure epidemiology trends Review the 2017 Stage C HF Guidelines Update Identify Stage D Advanced Heart Failure Appreciate Contemporary LVAD Therapy Recognize some temporary mechanical support technologies in the critically ill patient 10/23/17 3

4 Heart Failure Burden 1. JACC HF. 2013;1: Rose EA, et al. Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med. Nov. 2001;5;345(20): Rogers, Butler, Lansman, et al. J Am Coll Cardiol. 2007;50: Hershberger, Nauman, Walker, et al. J Card Fail. 2003;22: Gorodeski, Chu, Reese, et al. Circ Heart Fail. 2009;2: Data on file. Pleasanton, Calif: Thoratec Corp.

5 Heart Failure Natural History

6 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure

7 Citation This slide set was adapted from the 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure (Journal of the American College of Cardiology). Published on April 28, 2017, available at: Yancy, et. al. ACC/AHA/HFSA 2017 Heart Failure Focused Update The full-text guidelines are also available on the following Web sites: American College of Cardiology ( American Heart Association (professional.heart.org) Heart Failure Society of America(

8 Treatment of HF Stages A Through D Stage C

9 Treatment of HFrEF Stage C and D Hydral-Nitrates green box: The combination of ISDN/HYD with ARNI has not been robustly tested. BP response should be carefully monitored. See 2013 HF guideline. Participation in investigational studies is also appropriate for stage C, NYHA class II and III HF. ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor-blocker; ARNI, angiotensin receptor-neprilysin inhibitor; BP, blood pressure; bpm, beats per minute; C/I, contraindication; COR, Class of Recommendation; CrCl, creatinine clearance; CRT-D, cardiac resynchronization therapy device; Dx, diagnosis; GDMT, guideline-directed management and therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter-defibrillator; ISDN/HYD, isosorbide dinitrate hydral-nitrates; K+, potassium; LBBB, left bundle-branch block; LVAD, left ventricular assist device; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NSR, normal sinus rhythm; and NYHA, New York Heart Association.

10 Neprilysin Inhibition (ARNI: LCZ696) sacubatril-valsartan

11 Simplified schematic of the renin angiotensin aldosterone system. von Lueder T G et al. Circ Heart Fail. 2013;6:

12 Simplified schematic of the natriuretic peptide system (NPS). von Lueder T G et al. Circ Heart Fail. 2013;6:

13 PARADIGM HF

14 Kaplan Meier Curves for Key Study Outcomes, According to Study Group. McMurray JJ et al. N Engl J Med DOI: /NEJMoa

15 Primary and Secondary Outcomes. McMurray JJ et al. N Engl J Med DOI: /NEJMoa

16 Pharmacological Treatment for Stage C HF With Reduced EF Renin-Angiotensin System Inhibition With ACE-Inhibitor or ARB or ARNI COR LOE Recommendations I ACE-I: A ARB: A ARNI: B-R The clinical strategy of inhibition of the renin-angiotensin system with ACE inhibitors (Level of Evidence: A), OR ARBs (Level of Evidence: A), OR ARNI (Level of Evidence: B-R) in conjunction with evidence-based beta blockers, and aldosterone antagonists in selected patients, is recommended for patients with chronic HFrEF to reduce morbidity and mortality. Comment/ Rationale NEW: New clinical trial data prompted clarification and important updates.

17 Pharmacological Treatment for Stage C HF With Reduced EF Renin-Angiotensin System Inhibition With ACE-Inhibitor or ARB or ARNI COR LOE Recommendations I ARNI: B-R In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality. Comment/ Rationale NEW: New clinical trial data necessitated this recommendation.

18 Pharmacological Treatment for Stage C HF With Reduced EF Renin-Angiotensin System Inhibition With ACE-Inhibitor or ARB or ARNI COR LOE Recommendations III: Harm B-R ARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor. ARNI should not be III: Harm C-EO administered to patients with a history of angioedema. Comment/ Rationale NEW: Available evidence demonstrates a potential signal of harm for a concomitant use of ACE inhibitors and ARNI. NEW: New clinical trial data.

19 Pharmacological Treatment for Stage C HF With Reduced EF Ivabradine COR LOE Recommendations IIa B-R Ivabradine can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II-III) stable chronic HFrEF (LVEF 35%) who are receiving GDEM*, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest. Comment/ Rationale NEW: New clinical trial data. *In other parts of the document, the term GDMT has been used to denote guideline-directed management and therapy. In this recommendation, however, the term GDEM has been used to denote this same concept in order to reflect the original wording of the recommendation that initially appeared in the 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.

20 HFpEF Trends in Heart Failure N Engl J Med 2006;355:251-9.

21 Trends in HF N Engl J Med 2006;355:251-9.

22 Response to treatment HFrEF vs HFpEF Barry A. Borlaug, and Margaret M. Redfield Circulation. 2011;123:

23 *Electrical and Mechanical Repolarization Heterogeneity Shah, A. M. & Pfeffer, M. A. (2012) The many faces of heart failure with preserved ejection fraction Nat. Rev. Cardiol. doi: /nrcardio

24 Pharmacological Treatment for Stage C HF With Preserved EF COR LOE Recommendations I I B C Systolic and diastolic blood pressure should be controlled in patients with HFpEF in accordance with published clinical practice guidelines to prevent morbidity Diuretics should be used for relief of symptoms due to volume overload in patients with HFpEF. Comment/ Rationale 2013 recommendatio n remains current recommendatio n remains current.

25 Pharmacological Treatment for Stage C HF With Preserved EF COR LOE Recommendations IIb IIb B-R B In appropriately selected patients with HFpEF (with EF 45%, elevated BNP levels or HF admission within 1 year, estimated glomerular filtration rate >30 ml/min, creatinine <2.5 mg/dl, potassium <5.0 meq/l), aldosterone receptor antagonists might be considered to decrease hospitalizations. The use of ARBs might be considered to decrease hospitalizations for patients with HFpEF. Comment/ Rationale NEW: Current recommendation reflects new RCT data recommendation remains current.

26 Important Comorbidities in HF Anemia

27 Anemia COR LOE Recommendations IIb B-R In patients with NYHA class II and III HF and iron deficiency (ferritin <100 ng/ml or 100 to 300 ng/ml if transferrin saturation is <20%), intravenous iron replacement might be reasonable to improve functional status and QoL. Comment/ Rationale NEW: New evidence consistent with therapeutic benefit. III: No Benefit B-R In patients with HF and anemia, erythropoietin-stimulating agents should not be used to improve morbidity and mortality. NEW: Current recommendation reflects new evidence demonstrating absence of therapeutic benefit.

28 What About Heart Failure Complicated by Shock? Who is a Stage D HF Patient?

29 Cardiogenic Shock

30 Intra-Aortic Balloon Pump: 2015

31 IABP post AMI: SHOCK-II Trial

32 Temporary Support Devices

33 We Can t Transplant Everybody 1. Current estimates of adult patients with advanced heart failure (HF) in the United States, with projected left ventricular assist device (LVAD) candidates. U.S. population estimate is derived from U.S. Census data. Estimate of HF prevalence is derived from latest American Heart Association (AHA) statistics. 2. UNOS Website: 3. O Connell. Advanced Heart Failure Therapies Forum, Atlanta

34 Ventricular Assist Device: State of the Art 2017

35 MCS vs Medical Therapy

36 MCS vs Medical Therapy

37 Evolution of Devices

38 10 Main Points on LVAD LVAD: The Big Picture 2. LVAD: Hemodynamic Optimization 3. LVAD Device Trends LVAD Trial Data Summary & New Devices 5. Adverse Event Rate Trends 6. Quality of Life 7. Cost of Device Implantation 8. Cost Effectiveness 9. LVAD and Electrophysiology 10.The Future 10/23/17 38

39 1. LVAD: THE BIG PICTURE

40 10/23/17 40

41 2. LVAD: HEMODYNAMIC OPTIMIZATION

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43 3. LVAD IMPLANT TRENDS:

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46 4. LANDMARK TRIALS & NEW TECHNOLOGY

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49 5. ADVERSE EVENT RATES

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51 6. QUALITY OF LIFE

52 Quality of Life Data: INTERMACS 10/23/17 52

53 7. COST: WHAT DRIVES COST?

54 What Drives the VAD Implant Cost? 10/23/17 54

55 Post Implant Length of Stay of Patients Discharged Alive Days Intermacs TUKH /23/17 55

56 8. COST-EFFECTIVENESS

57 DT LVAD: Costs, QALYs, ICER 10/23/17 57

58 Pulsatile to CF LVAD Transition 10/23/17 58

59 Beyond the Index Admission: Costs 10/23/17 59

60 9. LVAD & Electrophysiology

61 LVAD: EP Topics ICD Implantation Post-LVAD Tachy-therapies settings LV lead ON vs OFF Atrial fibrillation treatments VT Ablation 10/23/17 61

62 10. THE FUTURE

63 Future Developments & Challenges Driveline removal (totally internal LVAD) Minimally invasive implantation Continuous hemodynamic monitoring 10/23/17 63

64 10 Main Points on LVAD Heart failure epidemic: large and growing 2. Novel pharma and device therapies -ARNI to replace ARB/ACE-I -HCN blockers -ambulatory PA pressure monitoring devices 3. Lacking data / guidelines on HFpEF 4. System innovations are key 5. Refer early for Stage D HF patients 10/23/17 64

65 Andrew J. Sauer, MD Assistant Professor Director, Center for Heart Failure Medical Director, Heart Transplantation UNOS Primary Transplant Physician