1. Monica Colvin-Adams, MD Assistant Professor of Medicine Advanced Heart Failure and Transplantation University of Minnesota Compassionate Allowances Outreach Hearing on Cardiovascular Diseases and Multi-organ Transplantation

2.  5.8 million people in US in 2006  23 million worldwide  One year mortality up to 50% in advanced heart failure  At 40 years old, life-time risk is 1/5  Aging population  Improved treatment of cardiovascular disease Lloyd-Jones, D, Adams, RJ, Brown, TM, et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 2010; Clinical epidemiology of heart failure: public and private health burden.AUMcMurray JJ; Petrie MC; Murdoch DR; Davie APSOEur Heart J. 1998 Dec

6.  When symptoms become excessive despite optimal medical therapy  Class III/IV heart failure  Symptoms with minimal activity or at rest  Frequent hospitalizations  Hemodynamic instability  Low cardiac output  Fluid retention  Arrhythmias  Intractable angina

9.  Chronic Functional Impairment  Angina  Co-morbid conditions  Cachexia  Frequent/prolonged hospitalizations  Mechanical circulatory support

10.  Persistent functional impairment related to longstanding heart failure, prior surgeries, steroids  Multiple clinic visits  Delayed healing due to multiple sternotomies, medications  Infection  Rejection

11.  At least 14 clinic visits  12-14 biopsies  Cardiac rehabilitation  Early morbidity  Rejection 30% (ISHLT)  Infection 60% (CTRD)  Re-hospitalizations

12. ISHLT 2009

13.  Analyzes gene expression data  Identifies gene expression patterns in peripheral blood assoc. with acute cellular rejection  Translates complex signals into a score  2 months post-transplant

14. Mild Severe Cardiac biopsy is used to monitor for rejection and guide usage of immunosuppressive drugs Most US centers do 12-14 biopsies in year 1, 2-4 in years 2-5

15. Most Common Causes of Late Death Malignancy Graft failure Cardiac allograft vasculopathy (coronary artery disease) Morbidity 1 year (2000-2003) 10 years (1994-2008) Hypertension7698% Diabetes2737% Renal Dysfunction 2714% Chronic Dialysis ----5% Kidney Transplant ----1% Abnormal Lipids 7493% Cardiac Allograft Vasculopathy 52% ISHLT 2009 Post Transplant Morbidity

16. ISHLT 2009

17.  Reduced and does not return to “normal” after transplant  57% of patients still at NYHA class II-IV  Altered physiologic response of denervated heart to exercise  Glucocorticoids (steroids)  Deconditioning prior to transplant  Effect of heart failure on skeletal muscle Niset G, Hermans L, Depelcin P. Exercise and Heart Transplantation: a review. Sports Med 1991;12:359-379

18.  Arbitrary  Depends on type of job  Exposure  Functional limitations/Cardiac rehabilitation  Ability to maintain coverage  Economic and social stability

19. ISHLT 2009

20.  Advanced heart failure is associated with severe functional and even cognitive limitations  Heart transplantation is a “cure” for heart failure which offers a significant improvement in functional status and return to near-normal levels of functioning in most people  Heart transplantation represents a new medical condition  Due to associated co-morbidities, baseline functional impairment, and complications of transplant, transient and chronic disabilities can ensue at any time during transplant

21.  Modulation of donor/recipient interaction  Improved therapy for rejection  Earlier detection of rejection and coronary disease  Earlier implantation of LVADs/smaller devices  Less reliance on transplantation Mechanical Circulatory Support