1. Major Medical Decisions in Advanced Heart Failure G. Michael Felker, MD, MHS, FACC, FAHA Chief, Heart Failure Section Duke University School of Medicine

2. Disclosures Grant Support and/or Consulting –NIH/NHLBI –Novartis –Amgen –Trevena –Roche Diagnostics –Otsuka –Celladon –St Judes –Singulex

4. Allen, LA et al. Circulation, 2012

5. Advanced Heart Failure 300 million 2.6% w/ HF (7 milllion) 50% sys HF 5% NYHA IV (150- 200K) 25% NYHA III 10% NYHA IIIB (300- 350K) IIIB+IV (250-300K) [<75 yrs] Miller LW. Circulation 2011

6. Allen L A et al. Circulation 2012 Variable Clinical Course of Heart Failure

7. Defining Options  Medical decision making is not a menu where the patient choses from among all available treatment options  Clinicians are responsible for defining the range of medically appropriate options.  Presentation of options should include:  alternative approaches  range of anticipated outcomes, including QoL  “what if?” scenarios

8. Typical Medical Decisions in Advanced Heart Failure Should we place an ICD? Should we list for heart transplant? Should we place a ventricular assist device as destination therapy? Should we involve palliative care?

9. ICDs in Chronic HF HF EtiologyIschemic: 100%Ischemic:59% Non-ischemic:41% Non-ischemic: 100% Ischemic: 52% Non-ischemic:48% NYHA ClassI/II/III (35%/35%/30%) III/IV (87%/13%) I/II/III (20%/60%/20%) II/III (71%/29%) LVEF< 30%< 35% No. Pts123215204582521 Follow-Up2 months12 months24 months45 months NNT17141714 Hazard Ratio0.690.640.660.77 P=0.007 P=0.065 P=0.004 P=0.016

10. Device Therapy for Stage C HFrEF ICD therapy is recommended for primary prevention of SCD to reduce total mortality in selected patients with nonischemic DCM or ischemic heart disease at least 40 days post-MI with LVEF of 35% or less, and NYHA class II or III symptoms on chronic GDMT, who have reasonable expectation of meaningful survival for more than 1 year. ICD therapy is recommended for primary prevention of SCD to reduce total mortality in selected patients at least 40 days post- MI with LVEF less than or equal to 30%, and NYHA class I symptoms while receiving GDMT, who have reasonable expectation of meaningful survival for more than 1 year. I IIaIIbIII I IIaIIbIII

11. Device Therapy for Stage C HFrEF The usefulness of implantation of an ICD is of uncertain benefit to prolong meaningful survival in patients with a high risk of nonsudden death as predicted by frequent hospitalizations, advanced frailty, or comorbidities such as systemic malignancy or severe renal dysfunction. I IIaIIbIII *Counseling should be specific to each individual patient and should include documentation about the potential for sudden death and non-sudden death from HF or non-cardiac conditions. Information should be provided about the efficacy, safety, and potential complications of an ICD and the potential for defibrillation to be inactivated if desired in the future, notably when a patient is approaching the end of life.

12. Primary Prevention ICD in context Out of 100 patients with an ICD implanted for primary prevention and followed for 4 years: –70 will never receive a shock –Of the 30 who do receive a shock, 13 of those shocks will be inappropriate –17 will have an appropriate shock that prevents SCD –10 of those pts will go onto die of something else –7 lives will be saved by implanting an ICD 14 ICD’s will be implanted to save 1 life (NNT = 14) Extrapolated from SCD-HeFT results

13. ICD Take Home Message ICD clearly improve survival in well defined groups of patients with heart failure Data on ICD therapy in patients with more advanced HF is very limited Important limitations of ICD therapy –ICDs do not improve symptoms or QOL –ICDs may decrease QOL (frequent shocks) –ICDs are designed to identify and treat a specific type of mortal event (ventricular tachy-arrhythmias)

14. Typical Medical Decisions in Advanced Heart Failure Should we place an ICD? Should we list for heart transplant? Should we place a ventricular assist device as destination therapy? Should we involve palliative care?

17. Cardiac Transplantation Evaluation for cardiac transplantation is indicated for carefully selected patients with stage D HF despite GDMT, device, and surgical management. I IIaIIbIII

18. Cardiac Transplantation Evaluation Complete history and physical examination CBC, BMP, LFT, coags, UA Serologic testing for syphilis, HIV, hepatitis B & C, CMV,EBV, VZV, toxo Tb skin testing ABO, HLA typing, panel reactive antibody screening 12 lead ECG Echocardiogram Chest xray Cardiopulmonary exercise testing Right heart catheterization with vasodilator challenge if appropriate Age appropriate cancer screening PFTS Carotid ultrasound VQ scan Dental evaluation Psychosocial evaluation Social work evaluation Nutrition consult Financial Evaluation

19. Transplant is Epidemiologically Trivial 300 million 2.6% w/ HF (7 milllion) 50% sys HF 5% NYHA IV (150- 200K) 25% NYHA III 10% NYHA IIIB (300- 350K) IIIB+IV (250-300K) [<75 yrs] Miller LW. Circulation 2011 ~2300 transplant/year

20. Typical Medical Decisions in Advanced Heart Failure Should we place an ICD? Should we list for heart transplant? Should we place a ventricular assist device as destination therapy? Should we involve palliative care?

21. Improving Survival with Continuous Flow LVAD

22. Improvement in Functional Capacity with Mechanical Support Rogers, JG et al. JACC 2010

23. Changing Landscape of Mechanical Support Stewart and Stevenson. Circulation 2011;123:1559-68.

24. Landscape of potential VAD patients INTERMACS Profiles NYHA classifications Class IIIClass IIIb/IVClass IV AHA/ACC classification Stage CStage D 1234567 Approved Range of HM II DT Approval and CMS Coverage Less SickSick INTERMACS 4: Resting symptoms on oral therapy at home General Range of Market Adoption Not Broadly AdoptedGenerally Accepted Ambulatory Class IIIB and IV ROADMAP INTERMACS 5: Exertion intolerant INTERMACS 6: Walking Wounded

25. Limitations of of LVAD Therapy Right heart failure Pump thrombosis Stroke Recurrent GI bleeding Arrhythmias Aortic insufficiency Drive line infections

26. Mechanical Circulatory Support MCS use is beneficial in carefully selected* patients with stage D HFrEF in whom definitive management (e.g., cardiac transplantation) or cardiac recovery is anticipated or planned. Nondurable MCS, including the use of percutaneous and extracorporeal ventricular assist devices (VADs), is reasonable as a “bridge to recovery” or a “bridge to decision” for carefully selected* patients with HFrEF with acute, profound hemodynamic compromise. Durable MCS is reasonable to prolong survival for carefully selected* patients with stage D HFrEF. I IIaIIbIII I IIaIIbIII I IIaIIbIII

27. Re-hospitalizations after LVAD Smedira, N. et al. JACC-Heart Failure, 2013 Total ReadmissionsHospital Days

28. The Importance of Frailty Patient Selection for Advanced Heart Failure Therapy Flint, KM. Circ Heart Fail 2012;5:286-93

29. “…it is challenging to locate the intersection of patients who face high mortality without LVAD and yet can look forward to good outcomes with LVAD.” Stewart and Stevenson. Circulation 2011.

30. LVAD Take Home Destination LVAD therapy can provide substantial improvement in survival and functional capacity in selected patients with advanced heart failure It is also associated with a multiple major morbidities and a high risk of unplanned rehospitalization Patient selection with attention to those comorbidities likely to be improved by VAD therapy vs. those not is key

31. Other Important Considerations Even non-cardiac procedures may lead to progressive heart failure and cardiogenic shock Many ‘temporary’ forms of support may be associated with failure to wean and ‘dependence’ –Cardiopulmonary bypass –Inotropic therapy –IABP –Mechanical Ventilation Need for discussion of “what if” outcomes where feasible in advance

32. Typical Medical Decisions in Advanced Heart Failure Should we place an ICD? Should we list for heart transplant? Should we place a ventricular assist device as destination therapy? Should we involve palliative care?

33. Palliative Care is: Specialized medical care for people with serious illness Relief from symptoms, pain and stress – whatever the diagnosis Improve quality of life for both patient and family A team that provides an extra layer of support Appropriate at any age and at any stage of illness –Can be provided together with curative treatment

34. Palliative Care Models Medicare Hospice Benefit Life Prolonging Care Old Palliative Care Bereavement Hospice Care Life Prolonging Care New Diagnosis of Serious Illness End of Life

35. Shared Decision Making “The process through which clinicians and patients share information with each other and work toward decisions about treatment chosen from medically reasonable options aligned with patients’ values, goals, and preferences.”