1. JoAnn Lindenfeld, MD Professor of Medicine Medical Director, Cardiac Transplant Program Associate Director, Center for Women’s Health Research University of Colorado Frailty and Quality-Adjusted Survival MEDAMACS AND INTERMACS

2. What is frailty and how is it measured? Why is frailty important in LVAD patients? What do we know about frailty in LVAD patients? What about INTERMACS and MEDAMACS? Frailty and Quality-Adjusted Survival MEDAMACS AND INTERMACS

3. Frailty Decline in physiological reserve Impaired Resistance to stressors Incomplete Recovery Increased morbidity and mortality Bergman H et al. J Gerontol A Biol S ci Med Sci 2007;62:731-7

4. Frailty is not always an “eyeball” impression In fact frail patients are more likely to have a high BMI and central adiposity which masks “sarcopenia” Afilalo J et al. JACC 2010;56L1668-76. Gallagher d AJP Endo 2000;297:E366-75 Barzilay JL Arch Int MEd2007;167:635-41

5. There are a Number of Ways to Measure Frailty Frailty phenotype 1 Frailty index 2 1Fried LP et a. J Gerontol Collab Res Group 2001;56:146-5 2Rockwood K et al. CMAJ 2005; 173:489-95

6. Fried Frailty Phenotype Frailty MeasureCriteriaScoring System Validated Physical Performance Measures Fried Criteria1.Unintentional weight loss 2.Low grip strength 3.Self-reported exhaustion 4.Slow gait speed measured at usual pace over 15 feet 5.Low self-reported physical activity  0 criteria met: robust or not frail  1-2 criteria met: intermediate frail  ≥ 3 criteria met: frail Fried LP et al. J Gerontol A. Biol Sci Med 2001;56: M146-56; Banden-Roche K et al J Gerontol a Biol Sci Med Sci 2006;61:262-66;Xue Q-L et al. J Gerontol A. BiolSci Med Sci 2008; 63:984-990 A number of studies show that gait speed outperforms other criteria of frailty

7. INTERMACS and MEDAMACs 15 foot gait speed Instruct to “Walk at your comfortable pace” until a few steps past the 5-meter mark (should not start to slow down before) Begin each trial on the word “Go” Start the timer with the first footfall after the 0-meter line Stop the timer with the first footfall after the 5-meter line Frailty is defined by the time to walk 15 feet* Fifteen foot Gait Speed Test

8. Frailty Index A frailty index will be able to be constructed with a number of other “health deficits” already measured in INTERMACS and MEDACMACs These “health deficits” include co-morbidities captured in INTERMACS and may also include signs, symptoms, nutritional indices. Rockwood K Mitinski A. BMC Geriatr 2008;8:24-34

9. Cumulative deficit indexCut-points 1. Need help preparing mealsYes = 1, No = 0 2. Need help feeding yourselfYes = 1, No = 0 3. Need help dressing yourselfYes = 1, No = 0 4. Need help using the toiletYes = 1, No = 0 5. Need help with housekeepingYes = 1, No = 0 6. Need help climbing stairsYes = 1, No = 0 7. Need help bathingYes = 1, No = 0 8. Need help walkingYes = 1, No = 0 9. Need help using transportationYes = 1, No = 0 10. Need help getting in and out of bedYes = 1, No = 0 11. Need help managing medicationsYes = 1, No = 0 12. Depend on assistive devices (walker, cane, etc.) or other people to perform activities of daily life Yes = 1, No = 0 13. Dependent on a device for normal breathing Yes = 1, No = 0 14. Climb 2 flights of stairs without rest No, cannot do at all = 1; Yes, with difficulty = 0.5; Yes with no difficulty = 0 15. Myocardial infarctionYes = 1, No = 0 16. DiabetesYes = 1, No = 0 17. Peripheral vascular diseaseYes = 1, No = 0 18. Cerebrovascular diseaseYes = 1, No = 0 19. Chronic obstructive pulmonary diseaseYes = 1, No = 0 20. UlcerYes = 1, No = 0 21. HemiplegiaYes = 1, No = 0 22. Moderate/severe renal insufficiencyYes = 1, No = 0 23. History of liver diseaseYes = 1, No = 0 24. Rheumatologic diseaseYes = 1, No = 0 25. History of malignancyYes = 1, No = 0 26. History of dementiaYes = 1, No = 0 27. HypertensionYes = 1, No = 0 28. HyperlipidemiaYes = 1, No = 0 29. Body mass index Underweight or obese = 1; overweight = 0.5; normal = 0 30. DepressionYes = 1, No = 0 31. AnemiaYes = 1, No = 0 Frailty(Deficit) Index Predicts Mortality and Rehospitalizations Dunlay SM et al. J HLTx 2014;33:359-65 Mortality and Rehospitalization (0.32 = frail, 0.23 to 0.32 = intermediate frail, <0.23 = not frail ).

10. Chung CJ et al. J Card Failure 2014;20:310-15 Frailty (Handgrip) Predicts Mortality and Improves post LVAD n = 72 n = 31 n = 26

11. INTERMACS AND MEDAMACS Both Frailty Phenotype and Frailty Index are Available Frailty phenotype = Gait speed Frailty index = Can come up with multiple indices based on demographics, comorbidities, and labs

12. MEDAMACS Baseline A and Baseline B (n = 53) CharacteristicBaseline ABaseline B Gait Speed (M/sec)N=36N=31 mean1.0 (0.5)1.1(0.4) median1.0(.7-1.2)1.1(0.9-1.4) 6 minute walk Mean(SD)264.3(129)248.1(127.8) Median(IQR)280(182.9-321.3)274.9(130.1-337.7)

13. INTERMACS AND MEDAMACS Both Frailty Phenotype and Frailty Index are Available How closely does gait speed (frailty phenotype) correlate with frailty indices? Does heart failure alone cause frailty? Is frailty predictive of heart failure progression? Do either frailty phenotype or index predict irreversibility of frailty? What outcomes do the frailty phenotype and indices predict—are they different? (eg respiratory failure, recovery to home) How closely does frailty correlate with quality of life?