1. Coordinator Training Session, March 11, 2012 1  Robert Kormos, MD INTERMACS Co-Principal Investigator GO TO PAGE 58 in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

2. Coordinator Training Session, March 11, 2012 2 Device Malfunction Device malfunction denotes a failure of one or more of the components of the MCSD system which either directly causes or could potentially induce a state of inadequate circulatory support (low cardiac output state) or death. The manufacturer must confirm device failure. A failure that was iatrogenic or recipient-induced will be classified as an Iatrogenic/Recipient-Induced Failure. Device failure should be classified according to which components fails as follows: 1)Pump failure (blood contacting components of pump and any motor or other pump actuating mechanism that is housed with the blood contacting components). In the special situation of pump thrombosis, thrombus is documented to be present within the device or its conduits that result in or could potentially induce circulatory failure. 2) Non-pump failure (e.g., external pneumatic drive unit, electric power supply unit, batteries, controller, interconnect cable, compliance chamber) The Adverse Event: Device Malfunction Form is to be collected at time of event. FDA has set forth regulations regarding these events. For the purposes of submitting adverse event device malfunction information to the FDA, you must enter any device malfunction event that occurs within 72 hours of the event. Service provided by: INTERMACS INTERMACS Coordinator Training March 2012

3. Coordinator Training Session, March 11, 2012 3 Device Malfunction:  Specific for each device  Added: End of pump life for causative factor  Page 58 & 59 INTERMACS Coordinator Training March 2012

4. Coordinator Training Session, March 11, 2012 4 INTERMACS Coordinator Training March 2012

5. Coordinator Training Session, March 11, 2012 5 INTERMACS Coordinator Training March 2012

6. Coordinator Training Session, March 11, 2012 6  Lynne Stevenson, MD INTERMACS Co-Principal Investigator GO TO PAGE 60 in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

7. Coordinator Training Session, March 11, 2012 7 Major Infection A clinical infection accompanied by pain, fever, drainage and/or leukocytosis that is treated by anti-microbial agents (non- prophylactic). A positive culture from the infected site or organ should be present unless strong clinical evidence indicates the need for treatment despite negative cultures. The general categories of infection are listed below: Localized Non-Device Infection Infection localized to any organ system or region (e.g. mediastinitis) without evidence of systemic involvement (See sepsis definition), ascertained by standard clinical methods and either associated with evidence of bacterial, viral, fungal or protozoal infection, and/or requiring empirical treatment. Percutaneous Site and/or Pocket Infection A positive culture from the skin and/or tissue surrounding the drive line or from the tissue surrounding the external housing of a pump implanted within the body, coupled with the need to treat with antimicrobial therapy when there is clinical evidence of infection such as pain, fever, drainage, or leukocytosis. Internal Pump Component, Inflow or Outflow Tract Infection Infection of blood-contacting surfaces of the LVAD documented by positive site culture. (There should be a separate data field for paracorporeal pump that describes infection at the percutaneous cannula site, e.g. Thoratec PVAD). Sepsis Evidence of systemic involvement by infection, manifested by positive blood cultures and/or hypotension. INTERMACS Coordinator Training March 2012

8. Coordinator Training Session, March 11, 2012 8 Major Infection  Page 60 Causative/Contributing Factors: REMOVED INTERMACS Coordinator Training March 2012

9. Coordinator Training Session, March 11, 2012 9  Frank Pagani, MD INTERMACS Co-Principal Investigator GO TO PAGE 61 in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

10. Coordinator Training Session, March 11, 2012 10 Neurological Dysfunction Any new, temporary or permanent, focal or global neurological deficit ascertained by a standard neurological examination (administered by a neurologist or other qualified physician and documented with appropriate diagnostic tests and consultation note). The examining physician will distinguish between a transient ischemic attack (TIA), which is fully reversible within 24 hours (and without evidence of infarction), and a stroke, which lasts longer than 24 hours (or less than 24 hours if there is evidence of infarction). The NIH Stroke Scale (for patients > 5 years old) must be re-administered at 30 and 60 days following the event to document the presence and severity of neurological deficits. Each neurological event must be subcategorized as: 1)Transient Ischemic Attack (acute event that resolves completely within 24 hours with no evidence of infarction) 2)Ischemic or Hemorrhagic Cardiovascular Accident/CVA (event that persists beyond 24 hours or less than 24 hours associated with infarction on an imaging study.) INTERMACS Coordinator Training March 2012

11. Coordinator Training Session, March 11, 2012 11 Causative/Contributing Factors: REMOVED Neurological Dysfunction  Page 61 INTERMACS Coordinator Training March 2012

12. Coordinator Training Session, March 11, 2012 12 Neurological categories expanded….more choices Location of CNS event expanded….more choices Description of clinical event….REMOVED Surgical and Drug Interventions….REMOVED INTERMACS Coordinator Training March 2012

13. Coordinator Training Session, March 11, 2012 13  Robert Kormos, MD INTERMACS Co-Principal Investigator GO TO PAGE 64 in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

14. Coordinator Training Session, March 11, 2012 14 MAJOR BLEEDING AN EPISODE OF SUSPECTED INTERNAL OR EXTERNAL BLEEDING THAT RESULTS IN ONE OR MORE OF THE FOLLOWING: 1. Death, 2. Re-operation, 3. Hospitalization, 4. Transfusion of red blood cells If TRANSFUSION IS SELECTED, then apply the following rules: During first 7 days post implant:  Adults (≥ 50 kg): ≥ 4U packed red blood cells (PRBC) within any 24 hour period during first 7 days post implant. After 7 days post implant  Any transfusion of packed red blood cells (PRBC) after 7 days following implant with the investigator recording the number of units given. Note: Hemorrhagic stroke is considered a neurological event and not as a separate bleeding event. INTERMACS Coordinator Training March 2012

15. Coordinator Training Session, March 11, 2012 15 Major Bleeding “episode”  Page 64 An “episode” may span several days. “It is not the transfusion that determines bleeding, but the recognized bleeding event.”---Dr. Kormos Transfusions for ANEMIA... Hemolysis & Hemorrhagic Stroke have their own AE Form INTERMACS Coordinator Training March 2012

16. Coordinator Training Session, March 11, 2012 16 Major Bleeding  Page 64 Causative/Contributing Factors: REMOVED INTERMACS Coordinator Training March 2012

17. Coordinator Training Session, March 11, 2012 17  Lynne Stevenson, MD INTERMACS Co-Principal Investigator GO TO PAGE 86,85 in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

18. Coordinator Training Session, March 11, 2012 18 Renal Dysfunction Two categories of renal dysfunction will be identified: Acute Renal Dysfunction Abnormal kidney function requiring dialysis (including hemofiltration) in patients who did not require this procedure prior to implant, or a rise in serum creatinine of greater than 3 times baseline or greater than 5 mg/dL (in children, creatinine greater than 3 times upper limit of normal for age) sustained for over 48 hours. Chronic Renal Dysfunction An increase in serum creatinine of 2 mg/dl or greater above baseline, or requirement for hemodialysis sustained for at least 90 days. Hepatic Dysfunction An increase in any two of the following hepatic laboratory values (total bilirubin, aspartate aminotransferase/AST and alanine aminotranferease/ALT) to a level greater than three times the upper limit of normal for the hospital, beyond 14 days post-implant (or if hepatic dysfunction is the primary cause of death). INTERMACS Coordinator Training March 2012

19. Coordinator Training Session, March 11, 2012 19  Now a Triggered Event  Page 70 This AE will be ‘triggered’ based creatinine > 5 mg/dL. INTERMACS Coordinator Training March 2012

20. Coordinator Training Session, March 11, 2012 20  Now a Triggered Event  Page 69 This AE will be ‘triggered’ based on SGPT/ALT > 190 u/L, Total Bilirubin > 5 mg/dL and SGOT/AST > 123 u/L INTERMACS Coordinator Training March 2012

21. Coordinator Training Session, March 11, 2012 21  Gail Mertz, RN INTERMACS Nurse Monitor GO TO PAGE 85 in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

22. Coordinator Training Session, March 11, 2012 22 Tier 2 Events: Asked During Each Follow-up & Rehospitalization  Pages 66-68 INTERMACS Coordinator Training March 2012

23. Coordinator Training Session, March 11, 2012 23 Cardiac Arrhythmias Any documented arrhythmia that results in clinical compromise (e.g., diminished VAD flow, oliguria, pre- syncope or syncope) that requires hospitalization or occurs during a hospital stay. Cardiac arrhythmias are classified as 1 of 2 types: 1) Sustained ventricular arrhythmia requiring defibrillation or cardioversion. 2) Sustained supraventricular arrhythmia requiring drug treatment or cardioversion Pericardial Fluid Collection Accumulation of fluid or clot in the pericardial space that requires surgical intervention or percutaneous catheter drainage. This event will be subdivided into those with clinical signs of tamponade (e.g. increased central venous pressure and decreased cardiac/VAD output) and those without signs of tamponade. INTERMACS Coordinator Training March 2012

24. Coordinator Training Session, March 11, 2012 24 Myocardial Infarction Two categories of myocardial infarction will be identified: Peri-Operative Myocardial Infarction The clinical suspicion of myocardial infarction together with CK-MB or Troponin > 10 times the local hospital upper limits of normal, found within 7 days following VAD implant together with ECG findings consistent with acute myocardial infarction. (This definition uses the higher suggested limit for serum markers due to apical coring at the time of VAD placement, and does not use wall motion changes because the apical sewing ring inherently creates new wall motion abnormalities.) Non-Perioperative Myocardial Infarction The presence at > 7 days post-implant of two of the following three criteria: a) chest pain which is characteristic of myocardial ischemia, b) ECG with a pattern or changes consistent with a myocardial infarction, and c) Troponin or CK (measured by standard clinical pathology/laboratory medicine methods) greater than the normal range for the local hospital with positive MB fraction (≥ 3% total CK). This should be accompanied by a new regional LV or RV wall motion abnormality on a myocardial imaging study. INTERMACS Coordinator Training March 2012

25. Coordinator Training Session, March 11, 2012 25 Psychiatric Episode Disturbance in thinking, emotion or behavior that causes substantial impairment in functioning or marked subjective distress requiring intervention. Intervention is the addition of new psychiatric medication, hospitalization, or referral to a mental health professional for treatment. Suicide is included in this definition. Respiratory Failure Impairment of respiratory function requiring reintubation, tracheostomy or (for patients older than age 5 years) the inability to discontinue ventilatory support within six days (144 hours) post-VAD implant. This excludes intubation for re-operation or temporary intubation for diagnostic or therapeutic procedures. INTERMACS Coordinator Training March 2012

26. Coordinator Training Session, March 11, 2012 26 Venous Thromboembolism Evidence of venous thromboembolic event (e.g. deep vein thrombosis, pulmonary embolism) by standard clinical and laboratory testing. Wound Dehiscence Disruption of the apposed surfaces of a surgical incision, excluding infectious etiology, and requiring surgical repair. INTERMACS Coordinator Training March 2012

27. Coordinator Training Session, March 11, 2012 27 Arterial Non-CNS Thromboembolic Event An acute systemic arterial perfusion deficit in any non-cerebrovascular organ system due to thromboembolism confirmed by one or more of the following: 1) standard clinical and laboratory testing 2) operative findings 3) autopsy findings This definition excludes neurological events. Other SAE An event that causes clinically relevant changes in the patient’s health (e.g. cancer). INTERMACS Coordinator Training March 2012

28. Coordinator Training Session, March 11, 2012 28 Hypertension New onset blood pressure elevation greater than or equal to 140 mm Hg systolic or 90 mm Hg diastolic (pulsatile pump) or 110 mm Hg mean pressure (rotary pump). Pediatric patients: for patients under 18 years of age weighing < 50 kg, hypertension is defined as systolic, diastolic, or mean blood pressure greater than the 95 th percentile for age which requires the addition of iv or oral therapy for management.  Triggered Event  Page 69 INTERMACS Coordinator Training March 2012

29. Coordinator Training Session, March 11, 2012 29  Robert Kormos, MD  Frank Pagani, MD INTERMACS Co-Principal Investigators GO TO PAGE 71 in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

30. Coordinator Training Session, March 11, 2012 30 Right Heart Failure Symptoms and signs of persistent right ventricular dysfunction [central venous pressure (CVP) > 18 mmHg with a cardiac index <2.3 L/min/m2 in the absence of elevated left atrial/pulmonary capillary wedge pressure (greater than 18 mmhg), tamponade, ventricular arrhythmias or pneumothorax] requiring RVAD implantation; or requiring inhaled nitric oxide or inotropic therapy for a duration of more than 1 week at any time after LVAD implantation.” LEVEL OF RIGHT HEART FAILURE Severe RHF: RVAD Moderate RHF: Inotrope or intravenous or inhaled pulmonary vasodilator (e.g. prostaglandin E or inhaled nitric oxide) Mild RHF: Meets 2 of the 4 clinical criteria listed below  CVP > 18 mmHg or mean RA pressure > 18 mmHg  CI < 2.3 L/min/MW 2 (by Swan)  Ascites or evidence of moderate to worse peripheral edema  Evidence of elevated CVP by echo (dilated VC, IVS with collapse), physical exam (signs of increased jugular venous pressure) INTERMACS Coordinator Training March 2012

31. Coordinator Training Session, March 11, 2012 31  Now a Triggered Event  Page 71 INTERMACS Coordinator Training March 2012

32. Coordinator Training Session, March 11, 2012 32 After the follow up form is submitted, this screen will appear for triggered events. New Version INTERMACS Coordinator Training March 2012

33.  Kathy Grady, PhD, APN Chair of Quality of Life Committee  Darlene Schmuhl, RN Cleveland Clinic Coordinator Training Session, March 11, 2012 GO TO PAGE 72 in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

34. Mobility I have no problems in walking about  I have some problems in walking about  I am confined to bed  Self-Care I have no problems with self-care  I have some problems washing or dressing myself  I am unable to wash or dress myself  Usual Activities (e.g. work, study, housework, family or leisure activities) I have no problems with performing my usual activities  I have some problems with performing my usual activities  I am unable to perform my usual activities  Pain/Discomfort I have no pain or discomfort  I have moderate pain or discomfort  I have extreme pain or discomfort  Anxiety/Depression I am not anxious or depressed  I am moderately anxious or depressed  I am extremely anxious or depressed  EQ-5D-3L Health Questionnaire English version for the US Patient Instruments: EQ-5D-3L EuroQol Group, 1990 INTERMACS Coordinator Training March 2012

35. Additional Patient Questions (page 4, attached to the EQ-5D-3L) 2 Versions: (sample questions) PRE IMPLANT FORM Please answer questions #1-8 below, so as to provide with us with some additional information. 7. How confident are you that you can do the tasks and activities needed to manage your heart failure so as to reduce how much having heart failure affects your everyday life? 1 2 3 4 5 6 7 8 9 10 Not at all confident Totally confident 8. How satisfied are you with the outcome of your therapy for heart failure during the past 3 months? 1 2 3 4 5 6 7 8 9 10 Not satisfied Very satisfied POST IMPLANT FORM Please answer questions #1-9 below, so as to provide with us with some additional information. 7. How confident are you that you can do the tasks and activities needed to manage your ventricular assist device so as to reduce how much having a ventricular assist device affects your everyday life? 1 2 3 4 5 6 7 8 9 10 Not at all confident Totally confident 8. How satisfied are you with the outcome of your ventricular assist device surgery, during the past 3 months? 1 2 3 4 5 6 7 8 9 10 Not satisfied Very satisfied 9. If you had to do it all over again, would you decide to have a ventricular assist device know what you know now? 12345 definitely no probably no not sure probably yes definitely yes INTERMACS Coordinator Training March 2012

36. Kansas City Cardiomyopathy Questionnaire 23 items (measures health status in heart failure patients) Dimensions and 2 summary scores - symptoms (frequency & severity)- self-efficacy - physical limitations- quality of life - social limitations Clinical summary: Physical limitations and symptoms Overall summary: Clinical summary + social limitations and QOL Response Format - Likert scale (5-7 point range) Scoring - range = 0-100; higher score = fewer symptoms, better function, better QOL Psychometrics KCCQ, Spertus J, et al. 2000 - reliable and valid in HF patients KCCQ, Spertus J, et al. 2000 INTERMACS Coordinator Training March 2012

37. Schedule for Data Collection Pre implant Post Implant 3 months6 months Q 6 months thereafter QOLXXXX Administer the pre implant QOL forms as soon as possible after consent is obtained. If consent is obtained after MCS implant, administer the first post- implant forms at the next time period due (e.g., 3 months) INTERMACS Coordinator Training March 2012

38. Procedures Administer the QOL forms to adult patients (> 19 years). Patients are to complete forms via self-report and independently - If unable, the questionnaires may be read to patients by the coordinator or family members (no coaching) - Indicate if forms were self-administered or completed verbally on the forms Research coordinators will review all questionnaires for data errors (e.g., missing or unclear data) with patients at the time of forms completion. - Corrections must be made with patients at that time. Regarding non-completion of questionnaires If patients do not complete questionnaires, research coordinators will enter the reason why. Missing QOL Data Form Sample reasons: _____ Too sick _____ No time / too busy _____ Coordinator too busy or forgot INTERMACS Coordinator Training March 2012

39. What is the best way to deal with missing data? INTERMACS Coordinator Training March 2012

40. Avoiding Missing data Statistical issues regarding missing data Fewer observations → loss of power Nonrandom missing data → bias Primary prevention Although there are analytic strategies for dealing with missing data, their use is much less satisfactory than initial prevention. Some missing data, such as that due to death, is not preventable. Note: a common reason for questionnaire non-completion is staff perception that the patient is too ill to complete questionnaires. To minimize bias by selecting out these patients, all patients (within reason) should be asked to complete questionnaires. Thus, missing data should be minimized for INTERMACS. Tips to encourage questionnaire completion: Educate patients about the importance of completing QOL questionnaires. E.g., “We want to know more about the quality of life of patients as they participate in this registry and the only way to know is to ask you. It takes about ___ minutes to complete the questionnaires.” Secondary prevention INTERMACS Coordinator Training March 2012

41. Months Post Implant Proportion of Patients Pre-implant 83% 69% 50% 8% 9% 0% 19% 11% 1% 34% 15% 1% 41 Primary Continuous Flow LVADs: June 2006 – March 2010 (n=1559) Alive (device in place) Txpl Dead Recovery INTERMACS Coordinator Training March 2012

42. Status of Patients at 1 year post implant by patient profile levels, n=1559 Patient Profile Levels (Pre-Implant) 1 2 3 4 5-7 Total EQ-5D status at 1 year n= 262 n=695 n=330 n=175 n=97 n=1559 1 Year Form not addressed* 157 377 169 86 45 834 Patient not seen in clinic No 4 20 12 9 5 50 1 yr Follow-up ‘Due’ 11 9 12 3 3 38 Patient Seen in clinic 90 289 137 77 44 637 Did Pt complete EQ-5D? Yes 46 169 91 51 29 386 Unknown 3 12 2 0 3 20 No 41 108 45 26 12 232 Reasons EQ-5D incomplete Too Sick 3 4 6 3 1 17 Pt unavailable 0 3 0 3 1 7 Did not contact 7 29 12 5 1 54 Unknown 12 35 10 7 4 68 Reason missing 9 7 4 3 1 24 Other 10 30 12 5 4 61 * Patient died, transplanted, recovery, device exchange or transferred before 1 year 42 Primary Continuous Flow LVADs: June 2006 – March 2010 (n=1559) INTERMACS Coordinator Training March 2012

43. Coordinator Training Session, March 11, 2012 43  Pages 72-74  All Adult patients should complete the QOL instruments.  New Addition: KCCQ  KCCQ: Kansas City Cardiomyopathy Questionnaire  Collected: pre-implant, 3 months, 6 months & q6 months thereafter INTERMACS Coordinator Training March 2012

44. Coordinator Training Session, March 11, 2012 44  Page 74  Please Read Administrative Reason Additions INTERMACS Coordinator Training March 2012

45. Coordinator Training Session, March 11, 2012 45  Jo Ann Lindenfield, MD GO TO PAGE 43 in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

46. Why do a 15 foot walk for gait speed It provides additional data to the V02 exercise test and the 6 minute walk It can often be done when V02 and 6 minute walk are not feasible It is highly predictive ( at least in those over 60 years) of mortality, duration of hospitalization, discharge to a SNF or NH, long term disability in community elderly and those undergoing cardiac surgery INTERMACS Coordinator Training March 2012

47. Gait Speed adds Predictive Ability to the STS Risk Score Afilalo J et al. JACC 2010; 56: 1668-76 INTERMACS Coordinator Training March 2012

48. How to perform the 15 foot walk A well lit unobstructed area used for the 6 minute walk You will time the first 15 feet of the 6 minute walk and the total 6 minutes You will need two stopwatches or a double stopwatch Mark end of 15 feet from “0” line Take the time to go from 0-15 feet and time for total 6 minute walk INTERMACS Coordinator Training March 2012

49. How to perform the 15 foot walk Subjects in comfortable walking clothing May use cane or walker If require IV pole will need another person Walk at a comfortable pace—do not slow down at the marker but continue for total of 6 minutes Patient’s foot is on the “0” marker Start on the word go Stop the stopwatch with first footfall after the 15 foot line Record time in tenths of seconds, i.e. 6.3 sec INTERMACS Coordinator Training March 2012

50. Coordinator Training Session, March 11, 2012 50  Kathy Grady, PhD, APN GO TO PAGE in the SITE USERS’ GUIDE INTERMACS Coordinator Training March 2012

51. Coordinator Training Session, March 11, 2012 51  Neurocognitive function is to be measured by the Trail-Making Part B test.  Patients age 19 years and older, at the time of implant will be asked to complete this test  Administered at pre-implant,post implant (3 months, 6 months and q 6 months therafter)  After the subject completes Part B, take the test sheet and record the time in seconds.  If the patient completes the test, but the test is considered invalid, select “completed but invalid (score not entered).” Do not allow the patient to retake the test. INTERMACS Coordinator Training March 2012