CASE 1 Existing SDTM Codelist Consensus Cardiac Classification

CASE 1 - Existing SDTM Codelist: Consensus Cardiac Classification System Test Code/Name • TEST = TIMI Flow: A grading system for coronary blood flow based on the classification developed by the Thrombolysis in Myocardial Infarction Group. It classifies coronary blood flow into four classes based upon the angiographic appearance of the blood vessels. • Response Codelist: TIMI Flow Responses TIMI GRADE 0 Thrombolysis in Myocardial Infarction Flow 0 No perfusion. There is no antegrade flow beyond the point of occlusion. (Chesebro JH, Knatterud GL, Roberts R, et al, Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase: Clinical findings through hospital discharge, Circulation 76, No. 1, 142 -154, 1987) TIMI GRADE 1 Thrombolysis in Myocardial Infarction Flow 1 Penetration without perfusion. Contrast material passes beyond the area of obstruction but "hangs up" and fails to opacify the entire coronary bed distal to the obstruction for the duration of the cineangiographic filming sequence. (Chesebro JH, Knatterud GL, Roberts R, et al, Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase: Clinical findings through hospital discharge, Circulation 76, No. 1, 142 -154, 1987) TIMI GRADE 2 Thrombolysis in Myocardial Infarction Flow 2 Partial perfusion. The contrast material passes across the obstruction and opacifies the coronary bed distal to the obstruction. However, the rate of entry of contrast material into the vessel distal to the obstruction or its rate of clearance from the distal bed (or both) is perceptibly slower than its entry into or clearance from comparable areas not perfused by the previously occluded vessel (e. g. , the opposite coronary artery or the coronary bed proximal to the obstruction). (Chesebro JH, Knatterud GL, Roberts R, et al, Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase: Clinical findings through hospital discharge, Circulation 76, No. 1, 142 -154, 1987) TIMI GRADE 3 Thrombolysis in Myocardial Infarction Flow 3 Complete perfusion. Antegrade flow into the bed distal to the obstruction occurs as promptly as into the bed from the involved bed and is as rapid as clearance from an uninvolved bed in the same vessel or the opposite artery. (Chesebro JH, Knatterud GL, Roberts R, et al, Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase: Clinical findings through hospital discharge, Circulation 76, No. 1, 142 -154, 1987) © CDISC 2014 1

CASE 2 – Existing SDTM Codelist: Consensus Cardiac Classification System Test Code/Name • Test = New York Heart Association Class: A finding associated with a patient based on the functional classification developed by the New York Heart Association (NYHA), for categorizing patients with defined or presumed cardiac disease. The classification system is based on the ability to engage in physical activity. The classification system comprises four classes, though NYHA Class III and Class IV are often aggregated for the purpose of outcomes analysis. • Response Codelist: New York Heart Association Classification NYHA CLASS I New York Heart Association Class I NYHA CLASS II New York Heart Association Class II NYHA CLASS III New York Heart Association Class III NYHA CLASS IV New York Heart Association Class IV © CDISC 2014 Without limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitations, or dyspnea. Slight limitation of physical activity. The patient is comfortable at rest. Ordinary physical activity results in fatigue, palpitations, or dyspnea. Marked limitation of physical activity. The patient is comfortable at rest. Less than ordinary activity causes fatigue, palpitations, or dyspnea. Inability to carry on any physical activity without discomfort. Heart failure symptoms are present even at rest or with minimal exertion. 2

CASE 3 – Existing SDTM Codelist: Consensus Cardiac Classification System Test Code/Name • Test = ACC/AHA Lesion Complexity Class: A classification system for coronary stenosis based upon characteristics that influence the difficulty of percutaneous coronary revascularization. • Response Codelist: Lesion Complexity ACC/AHA LESION COMPLEXITY SCORE A ACC/AHA LESION COMPLEXITY SCORE B Low Risk ACC/AHA LESION COMPLEXITY SCORE C High Risk © CDISC 2014 Medium Risk Discrete (less than 10 mm length) and concentric and readily accessible and non-angulated segment less than 45 degrees and smooth contour and little or no calcification and less than totally occlusive and not ostial in location and no major branch involvement and absence of thrombus. Tubular (10 -20 mm length) or eccentric or moderate tortuosity of proximal segment or moderately angulated segment, 45 -90 degrees or irregular contour or moderate to heavy calcification or ostial in location or bifurcation lesions requiring double guidewires or some thrombus present or total occlusion less than 3 months old. Diffuse (length greater than 2 cm) or excessive tortuosity of proximal segment or extremely angulated segments greater than 90 degrees or total occlusions greater than 3 months old and/or bridging collaterals or inability to protect major side branches or degenerated vein grafts with friable lesions. 3

CASE 4 – Existing SDTM Codelist: Consensus Cardiac Classification System Test Code/Name • Test = Killip Class: A finding associated with a patient based on the classification developed by Killip and Kimball, which classifies patients with myocardial infarction based on routine physical examination parameters, such as the presence or absence of rales, or a decreased systolic blood pressure. • Response Codelist: Killip Class Responses KILLIP CLASS I The absence of rales over the lung fields and absence of third heart sound (S 3). (ACC/AHA) KILLIP CLASS II The presence of rales over 50% or less of the lung fields or the presence of a third heart sound (S 3). (ACC/AHA) The presence of rales over more than 50% of the lung fields. (ACC/AHA) The presence of cardiogenic shock (systolic BP less than 90 mm Hg) for greater than 30 minutes, not responsive to fluid resuscitation alone, and felt to be secondary to cardiac dysfunction. (ACC/AHA) KILLIP CLASS III KILLIP CLASS IV © CDISC 2014 4

CASE 5 – Existing SDTM Codelist: Consensus Cardiac Classification System Test Code/Name • Test = Canadian CV Society Grading Scale: A finding associated with a patient based on the functional classification developed by the Canadian Cardiovascular Society (CCS), for categorizing patients with angina. The classification system comprises four classes, which are defined in terms of the level of physical activity associated with the subject's anginal symptoms. • Response Codelist: Canadian Cardiovascular Society Classification CCS CLASS 1 Canadian Cardiovascular Society Classification 1 Ordinary physical activity, such as walking or climbing stairs, does not cause angina. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation. CCS CLASS 2 Canadian Cardiovascular Society Classification 2 CCS CLASS 3 Canadian Cardiovascular Society Classification 3 Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly, walking uphill, walking or climbing stairs after meals, or in cold, in wind, or under emotional stress, or only during the few hours after awakening. Angina occurs on walking more than 2 blocks on the level and climbing more than 1 flight of ordinary stairs at a normal pace and in normal conditions. Marked limitations of ordinary physical activity. Angina occurs on walking 1 to 2 blocks on the level and climbing 1 flight of stairs in normal conditions and at a normal pace. CCS CLASS 4 Canadian Cardiovascular Society Classification 4 © CDISC 2014 Inability to perform any physical activity without discomfort - anginal symptoms may be present at rest. 5

CASE 6 – Existing SDTM Codelist: Subject Characteristic Test Code/Name • TEST = Skin Classification: A classification system used to categorize the sensitivity of a subject's skin to sunlight. • Response Codelist: Skin Classification TYPEI TYPE 1 Individuals who never tan and always sunburn if exposed to any appreciable amount of sunlight, primarily red headed individuals and lightly complected blondes. (Reference: Fitzpatrick TB: The validity and practicality of sun-reactive skin types I through VI. Arch. Dermatol. 1998 124: 869 -871) TYPEII TYPE 2 Individuals who frequently burn but are able to tan to a small degree after extended sun exposure. (Reference: Fitzpatrick TB: The validity and practicality of sun-reactive skin types I through VI. Arch. Dermatol. 1998 124: 869 -871) TYPEIII TYPE 3 TYPEIV TYPE 4 Individuals who burn infrequently and tan readily. (Reference: Fitzpatrick TB: The validity and practicality of sun-reactive skin types I through VI. Arch. Dermatol. 1998 124: 869 -871) Individuals who rarely burn and tan heavily with moderate sun exposures, especially individuals of Asian, American Indian, Mediterranean and Latin American descent. (Reference: Fitzpatrick TB: The validity and practicality of sun-reactive skin types I through VI. Arch. Dermatol. 1998 124: 869 -871) TYPEV TYPE 5 Individuals who have dark constitutive pigmentation but become noticeably darker with sun exposure, especially light complected black individuals, those of Indian descent. (Reference: Fitzpatrick TB: The validity and practicality of sun-reactive skin types I through VI. Arch. Dermatol. 1998 124: 869 -871) TYPEVI TYPE 6 Individuals who have the heaviest constitutive pigmentation, especially dark skinned black individuals. (Reference: Fitzpatrick TB: The validity and practicality of sun-reactive skin types I through VI. Arch. Dermatol. 1998 124: 869 -871) © CDISC 2014 6

CASE 7 – Existing SDTM Codelist: Hepatic Findings About Test Code/Name • Test = West Haven Hepatic Encephalopathy Grade: A grading system to describe the severity of hepatic encephalopathy based on the level of mental status, per the West Haven Criteria. • Response Codelist: West Haven Hepatic Encephalopathy Grade GRADE 0 Minimal - symptoms or pathological characteristics include minimal hepatic encephalopathy, lack of detectable changes in personality or behavior, minimal changes in memory, concentration and intellectual function, and absence of coordination asterixis. (Adapted from: Hepatic Encephalopathy. David C Wolf. http: //emedicine. medscape. com/article/186101 -overview) GRADE 1 Mild - symptoms or pathological characteristics include trivial lack of awareness, shortened attention span, impaired ability to perform addition or subtraction, hypersomnia, insomnia, or inversion of sleep pattern, euphoria, depression or irritability, mild confusion, slowing of ability to perform mental tasks. (Adapted from: Hepatic Encephalopathy. David C Wolf. http: //emedicine. medscape. com/article/186101 -overview. ) GRADE 2 Moderate - symptoms or pathological characteristics include lethargy or apathy, disorientation, inappropriate behavior, slurred speech, obvious asterixis, drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behavior, and intermittent disorientation, unsurely regarding time. (Adapted from: Hepatic Encephalopathy. David C Wolf. http: //emedicine. medscape. com/article/186101 -overview. ) GRADE 3 Severe - symptoms or pathological characteristics include somnolence with some arousability, inability to perform mental tasks, disorientation about time and place, marked confusion, amnesia, occasional fits of rage, present but incomprehensible speech. (Adapted from: Hepatic Encephalopathy. David C Wolf. http: //emedicine. medscape. com/article/186101 -overview. ) GRADE 4 Coma - symptoms or pathological characteristics include coma with or without response to painful stimuli. (Adapted from: Hepatic Encephalopathy. David C Wolf. http: //emedicine. medscape. com/article/186101 -overview. ) © CDISC 2014 7

CASE 8 – Existing SDTM Codelist: Cardiovascular Findings About Test Code/Name • • Test = Acute Myocardial Infarction Type: Categorization of the type of acute myocardial infarction. Response Codelist: Cardiovascular Findings About Results TYPE 1 MYOCARDIAL INFARCTION Spontaneous clinical syndrome related to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection, with resulting intraluminal thrombus, and leading to decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis. This classification requires a) detection of a rise and/or fall of cardiac biomarker values [preferably cardiac troponin (c. Tn)] with at least one value greater than 99 th percentile of the upper reference limit (URL) and b) at least one of the following: symptoms of myocardial ischemia; new or presumed new significant ST-segment-T wave (ST-T) changes or new left bundle branch block (LBBB) on the ECG; development of pathological Q waves on the ECG; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; identification of an intracoronary thrombus by angiography or autopsy. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525 -2538. ) TYPE 2 MYOCARDIAL INFARCTION Ischemic imbalance: Spontaneous clinical syndrome where a condition other than coronary artery disease contributes to an imbalance between myocardial oxygen supply and/or demand, e. g. coronary endothelial dysfunction, coronary artery spasm, coronary embolism, tachy-/brady-arrhythmias, anemia, respiratory failure, hypotension, and hypertension with or without left ventricular hypertrophy. This classification requires detection of a rise and/or fall of cardiac biomarker values [preferably cardiac troponin (c. Tn)] with at least one value greater than 99 th percentile of the upper reference limit (URL) and b) at least one of the following: symptoms of myocardial ischemia; new or presumed new significant ST-segment-T wave (ST-T) changes or new left bundle branch block (LBBB) on the ECG; development of pathological Q waves on the ECG; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525 -2538. ) Death, No Biomarkers: Death where symptoms suggestive of myocardial ischemia are present, and with (presumed) new ischemic changes or new LBBB on ECG, but where death occurs before cardiac biomarkers can be obtained, or before cardiac biomarker values could rise. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525 -2538. ) PCI Related: PCI Related Myocardial infarction associated with and occurring within 48 h of percutaneous coronary intervention, with elevation of cardiac biomarker values to greater than 5 x 99 th percentile of the upper reference limit (URL) in patients with normal baseline values (less than or equal to 99 th percentile URL), or a rise of cardiac biomarker values greater than or equal to 20% if the baseline values are elevated and are stable or falling. This classification also requires at least one of the following: symptoms of myocardial ischemia; new ischemic ECG changes or new LBBB; angiographic loss of patency of a major coronary artery or a side branch or persistent slow- or no-flow or embolization; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525 -2538. ) Stent Thrombosis: Myocardial infarction associated with stent thrombosis as detected by coronary angiography or at autopsy, where symptoms suggestive of myocardial ischemia are present, and with a rise and/or fall of cardiac biomarkers values, with at least one value greater than 99 th percentile of the upper reference limit. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525 -2538. ) TYPE 3 MYOCARDIAL INFARCTION TYPE 4 A MYOCARDIAL INFARCTION TYPE 4 B MYOCARDIAL INFARCTION TYPE 4 C MYOCARDIAL INFARCTION TYPE 5 MYOCARDIAL INFARCTION Stent Restenosis: Myocardial infarction associated with stent restenosis as detected by coronary angiography or at autopsy, occurring more than 48 h after percutaneous coronary intervention, without evidence of stent thrombosis but with symptoms suggestive of myocardial ischemia, and with elevation of cardiac biomarker values to greater than 99 th percentile of the upper reference limit (URL). This classification also requires the following: does not meet criteria for any other classification of myocardial infarction; presence of a greater than or equal to 50 percent stenosis at the site of previous successful stent PCI. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525 -2538. ) CABG Related: Myocardial infarction associated with and occurring within 48 h of coronary artery bypass graft surgery, with elevation of cardiac biomarker values to greater than 10 x 99 th percentile of the upper reference limit (URL) in patients with normal baseline cardiac biomarker values (less than or equal to 99 th percentile URL). This classification also requires at least one of the following: new pathologic Q waves or new LBBB on ECG; angiographic new graft or new native coronary artery occlusion; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525 -2538. ) © CDISC 2014 8

CASE 9 – Existing SDTM Codelist: Cardiovascular Findings About Test Code/Name • • Test = Health Care Encounter Type: Categorization of the type of healthcare encounter. Response Codelist: Cardiovascular Findings About Results HEART FAILURE HOSPITALIZATION An event where the patient is admitted to the hospital with a primary diagnosis of heart failure (HF), where the length of stay is at least 24 hours (or extends over a calendar date), where the patient exhibits new or worsening symptoms of HF on presentation, has objective evidence of new or worsening HF, and receives initiation or intensification of treatment specifically for HF. (Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, Fonarow GC, Jacobs JP, Jaff MR, Lichtman JH, Limacher MC, Mahaffey KW, Mehran, R, Nissen SE, Smith EE, Targum SL. 2014 ACC/AHA Key Data Elements and Definitions For Cardiovascular Endpoint Events In Clinical Trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular End Points Data Standards) J Am Coll Cardiol 2014; In Press) URGENT HEART FAILURE VISIT An event where the patient has an urgent, unscheduled office/practice or emergency department visit for a primary diagnosis of heart failure (HF) but is not admitted to the hospital, where the patient exhibits new or worsening symptoms of HF on presentation, has objective evidence of new or worsening HF, and receives initiation or intensification of treatment specifically for HF, with the exception that changes to oral diuretic therapy do no qualify as initiation or intensification of treatment. (Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, Fonarow GC, Jacobs JP, Jaff MR, Lichtman JH, Limacher MC, Mahaffey KW, Mehran, R, Nissen SE, Smith EE, Targum SL. 2014 ACC/AHA Key Data Elements and Definitions For Cardiovascular Endpoint Events In Clinical Trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular End Points Data Standards) J Am Coll Cardiol 2014; In Press) © CDISC 2014 9

CASE 10 – Existing SDTM Codelist: Cardiovascular Findings About Test Code/Name • • Test = Ischemic Evidence Type: Categorization of the type of objective evidence of new or worsening ischemia. Response Codelist: Cardiovascular Findings About Results CORONARY LESION ON ANGIOGRAPHY Angiographic evidence of new or worse greater than or equal to 70 percent lesion and/or thrombus in an epicardial coronary artery believed to be responsible for the myocardial ischemic symptoms/signs. (Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, Fonarow GC, Jacobs JP, Jaff MR, Lichtman JH, Limacher MC, Mahaffey KW, Mehran, R, Nissen SE, Smith EE, Targum SL. 2014 ACC/AHA Key Data Elements and Definitions For Cardiovascular Endpoint Events In Clinical Trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular End Points Data Standards) J Am Coll Cardiol 2014; In Press) CORONARY REVASCULARIZATION Need for coronary revascularization procedure (PCI or CABG) for the presumed culprit lesion(s). This criterion would be fulfilled if revascularization was undertaken during the unscheduled hospitalization, or subsequent to transfer to another institution without interceding home discharge. (Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, Fonarow GC, Jacobs JP, Jaff MR, Lichtman JH, Limacher MC, Mahaffey KW, Mehran, R, Nissen SE, Smith EE, Targum SL. 2014 ACC/AHA Key Data Elements and Definitions For Cardiovascular Endpoint Events In Clinical Trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular End Points Data Standards) J Am Coll Cardiol 2014; In Press) INDUCIBLE MYOCARDIAL ISCHEMIA Definite evidence of inducible myocardial ischemia believed to be responsible for the myocardial ischemic symptoms/signs, demonstrated by any of the following: a) an early positive exercise stress test, defined as ST elevation of greater than or equal to 2 mm ST depression prior to 5 mets, b) stress echocardiography (reversible wall motion abnormality), c) myocardial scintigraphy (reversible perfusion defect), d) MRI (myocardial perfusion deficit under pharmacologic stress). (Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, Fonarow GC, Jacobs JP, Jaff MR, Lichtman JH, Limacher MC, Mahaffey KW, Mehran, R, Nissen SE, Smith EE, Targum SL. 2014 ACC/AHA Key Data Elements and Definitions For Cardiovascular Endpoint Events In Clinical Trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular End Points Data Standards) J Am Coll Cardiol 2014; In Press) RESTING ECG CHANGES New or worsening ST or T wave changes on resting ECG (in the absence of confounders, such as LBBB or LVH), defined as either: a) Transient ST elevation (duration less than 20 minutes): new ST elevation at the J point in any two contiguous leads (other than leads V 2 -V 3) of greater than or equal to 0. 1 m. V. In leads V 2 -V 3, the following cut-points apply: greater than or equal to 0. 2 m. V in men greater than or equal to 40 years, greater than or equal to 0. 25 m. V in men less than 40 years, and greater than or equal to 0. 15 m. V in women, or b) ST depression and T-wave changes: new horizontal or down-sloping ST depression greater than or equal to 0. 05 m. V in two contiguous leads and/or new T inversion greater than or equal to 0. 3 m. V in two contiguous leads with prominent R wave or R/S ratio greater than 1. © CDISC 2014 10

CASE 11 – Existing SDTM Codelist: Cardiovascular Findings About Test Code/Name • Test = Stroke Type: Categorization of the type of stroke. • Response Codelist: Cardiovascular Findings About Results HEMORRHAGIC STROKE An acute episode of focal or global cerebral or spinal dysfunction caused by intraparenchymal, intraventricular, or subarachnoid hemorrhage. ISCHEMIC STROKE Ischemic stroke is defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of central nervous system tissue. UNDETERMINED STROKE An acute episode of focal or global neurological dysfunction caused by presumed brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction but with insufficient information to allow categorization as ischemic or hemorrhagic. © CDISC 2014 11

CASE 12 – Existing CC Codelist: Stent Thrombosis Coronary ARC Grade Test Code/Name • Test = STCG 01 -STC ARC Grade: A grading system to describe the coronary stent thrombosis per the classification schema described by the Academic Research Consortium. • Response Codelist: Stent Thrombosis, Coronary ARC Grade Responses STENT THROMBOSIS ARC GRADE DEFINITE Includes acute ischemic symptoms at rest, acute post ischemic ECG, positive biomarkers and pathological evidence. Definite stent thrombosis is considered to have occurred when there is either angiographic or pathological confirmation. Angiographic confirmation is the presence of a thrombus at coronary angiography that originates in the stent or in the segment 5 mm proximal or distal to the stent, with the presence of at least 1 of 3 clinical criteria within a 48 -hour time window: 1) acute onset of ischemic symptoms at rest; 2) new ischemic ECG changes that suggest acute ischemia; or 3) typical rise and fall in cardiac biomarkers. Pathological confirmation is evidence of recent thrombus within the stent determined at autopsy or via examination of tissue retrieved following thrombectomy. (Cutlip DE, Windecker S, Mehran R, et al. Clinical End Points in Coronary Stent Trials : A Case for Standardized Definitions. Circulation. 2007; 115: 2344 -2351) STENT THROMBOSIS ARC GRADE POSSIBLE Possible stent thrombosis is considered to have occurred with any unexplained death more than 30 days after intracoronary stenting. (Cutlip DE, Windecker S, Mehran R, et al. Clinical End Points in Coronary Stent Trials : A Case for Standardized Definitions. Circulation. 2007; 115: 2344 -2351) STENT THROMBOSIS ARC GRADE PROBABLE Includes death within 30 days and myocardial infarction of stent territory. Probable stent thrombosis is considered to have occurred after intracoronary stenting in the following situations: 1) any unexplained death within the first 30 days; or 2) irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause. (Cutlip DE, Windecker S, Mehran R, et al. Clinical End Points in Coronary Stent Trials : A Case for Standardized Definitions. Circulation. 2007; 115: 2344 -2351) © CDISC 2014 12

CASE 13 – Existing CC Codelist: Coronary Thrombus TIMI Grade Test Code/Name • Test = TIMG 01 -Coronary Thrombus TIMI Grade: Grade corresponding to thrombus development as defined in the grading system by the Thrombolysis in the Myocardial Infarction Group. • Response Codelist: Coronary Thrombus TIMI Grade Responses CORONARY THROMBUS TIMI GRADE 1 Possible thrombus present - angiography demonstrates characteristics such as reduced contrast density, haziness, irregular lesion contour or a smooth convex 'meniscus' at the site of total occlusion suggestive but not diagnostic of thrombus. (Gibson, C. M. , de Lemos, J. A. , Murphy, S. A. , Marble, S. J. , Mc. Cabe, C. H. , Cannon, C. P. , Antman, E. M. , Braunwald, E. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy Circulation. 2001; 103(21): 2550 -4. ) CORONARY THROMBUS TIMI GRADE 2 Small size definite thrombus, with greatest dimensions less than or equal to 1/2 vessel diameter. (Gibson, C. M. , de Lemos, J. A. , Murphy, S. A. , Marble, S. J. , Mc. Cabe, C. H. , Cannon, C. P. , Antman, E. M. , Braunwald, E. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy Circulation. 2001; 103(21): 2550 -4. ) CORONARY THROMBUS TIMI GRADE 3 Moderate size definite thrombus, with greatest linear dimension greater than 1/2 but less than 2 vessel diameters. (Gibson, C. M. , de Lemos, J. A. , Murphy, S. A. , Marble, S. J. , Mc. Cabe, C. H. , Cannon, C. P. , Antman, E. M. , Braunwald, E. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy Circulation. 2001; 103(21): 2550 -4. ) CORONARY THROMBUS TIMI GRADE 4 Large size definite thrombus, with the largest dimension greater than or equal to 2 vessel diameters. (Gibson, C. M. , de Lemos, J. A. , Murphy, S. A. , Marble, S. J. , Mc. Cabe, C. H. , Cannon, C. P. , Antman, E. M. , Braunwald, E. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy Circulation. 2001; 103(21): 2550 -4. ) CORONARY THROMBUS TIMI GRADE 5 Total vessel occlusion. (Gibson, C. M. , de Lemos, J. A. , Murphy, S. A. , Marble, S. J. , Mc. Cabe, C. H. , Cannon, C. P. , Antman, E. M. , Braunwald, E. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy Circulation. 2001; 103(21): 2550 -4. ) © CDISC 2014 13

CASE 14 – Existing CC Codelist: Coronary Artery Dissection NHLBI Grade Test Code/Name • Test = CADG 01 -Coronary Dissection NHLBI Grade : A grading system to describe coronary artery dissection per the NHLBI, American College of Cardiology, American Heart Association. • Response Codelist: Coronary Artery Dissection NHLBI Grade Responses CORONARY DISSECTION NHLBI GRADE A Minor radiolucencies within the lumen during contrast injection with no persistence after dye clearance. (Adapted from: Coronary artery angiographic changes after PTCA: Manual of Operations NHLBI PTCA Registry 1985 -6: 9) CORONARY DISSECTION NHLBI GRADE B Parallel tracts or double lumen separated by a radiolucent area during contrast injection with no persistence after dye clearance. (Adapted from: Coronary artery angiographic changes after PTCA: Manual of Operations NHLBI PTCA Registry 1985 -6: 9) CORONARY DISSECTION NHLBI GRADE C Extraluminal cap with persistence of contrast after dye clearance from the lumen. (Adapted from: Coronary artery angiographic changes after PTCA: Manual of Operations NHLBI PTCA Registry 1985 -6: 9) CORONARY DISSECTION NHLBI GRADE D Spiral luminal filling defect with delayed but complete distal flow. (Adapted from: Coronary artery angiographic changes after PTCA: Manual of Operations NHLBI PTCA Registry 1985 -6: 9) CORONARY DISSECTION NHLBI GRADE E New persistent filling defect with delayed antegrade flow. May represent thrombus. (Adapted from: Coronary artery angiographic changes after PTCA: Manual of Operations NHLBI PTCA Registry 1985 -6: 9) CORONARY DISSECTION NHLBI GRADE F Non-A-E types with total coronary occlusion and no distal antegrade flow. May represent thrombus. (Adapted from: Coronary artery angiographic changes after PTCA: Manual of Operations NHLBI PTCA Registry 1985 -6: 9) © CDISC 2014 14

CASE 15 – Existing CC Codelist: Stent Thrombus Coronary ARC Timing <Category> Test Code/Name • Test = STCT 01 -STC ARC Timing <Category>: Categorization of the timing of coronary stent thrombosis occurrence per the classification schema described by the Academic Research Consortium. • Response Codelist: Stent Thrombosis, Coronary, ARC Timing <Category> Responses STENT THROMBOSIS ARC ACUTE 0 to 24 hours after stent implantation. (Cutlip DE, Windecker S, Mehran R, et al. Clinical Endpoints in Coronary Stent Trials : A Case for Standardized Definitions. Circulation. 2007; 115: 2344 -2351) STENT THROMBOSIS ARC LATE Greater than 30 days to 1 year after stent implantation. (Cutlip DE, Windecker S, Mehran R, et al. Clinical Endpoints in Coronary Stent Trials : A Case for Standardized Definitions. Circulation. 2007; 115: 2344 -2351) STENT THROMBOSIS ARC SUBACUTE Greater than 24 hours to 30 days after stent implantation. (Cutlip DE, Windecker S, Mehran R, et al. Clinical Endpoints in Coronary Stent Trials : A Case for Standardized Definitions. Circulation. 2007; 115: 2344 -2351) STENT THROMBOSIS ARC VERY LATE Greater than 1 year after stent implantation. (Cutlip DE, Windecker S, Mehran R, et al. Clinical Endpoints in Coronary Stent Trials : A Case for Standardized Definitions. Circulation. 2007; 115: 2344 -2351) © CDISC 2014 15