Assays Pros and Cons AACB 2013 GOLD COAST QUEENSLAND AUSTRALIA

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1 Highly Sensitive Versus Sensitive Troponin Assays Pros and Cons AACB 2013 GOLD COAST QUEENSLAND AUSTRALIA Robert H. Christenson, Ph.D., DABCC, FACB 2013 AACC President Professor of Pathology Professor of Medical and Research Technology University of Maryland School of Medicine Baltimore, Maryland 1

2 Disclosures: Dr. Christenson Honoraria: Siemens, Critical Care Diagnostics, BG Medicine, Singulex Advisory: BG Medicine, Instrumentation Laboratories, Siemens, Singulex Grants: Critical Care Diagnostics, Radiometer, BG Medicine, Roche, Siemens, BRAHMS, Vital Diagnostics, Nanosphere, Becton Dickinson 2

3 When troponin is increased think heart Cardiac isoforms in blood = 3

4 Definition of Myocardial Infarction Small heart attacks are so common; they are almost a within t normal o a range. a Paul ldudley White, 1957 The Father of American Cardiology 99 03m o0 1, 1 4

5 The Next Generation Prior Gen commercial TnI Limit of detect ~ 0.1ng/ml 10% CV = 0.4 ng/ml Current commercial TnI Limit of detect ~ ng/ml 10% CV = ng/ml Next Gen Ultrasensitive Limit of detect ~ ng/ml 10% CV < ng/ml Tn (ng/ml) 5

6 Early vs. Later Generation ctni Current generation ctni Earlier generation ctni 6

7 Implementation of a Sensitive Troponin I Assay and Risk of Recurrent Myocardial Infarction and Death in Patients With Suspected Acute Coronary Syndrome Mills et al. JAMA. 2011;305(12):

8 Troponin Normal Reference Interval LoD for hstn assays LoD for sstn assays LoD for Sensitive Assays 99th 8

9 Dr. Robert Jesse, Cardiologist when troponin was a lousy assay it was a great test, but now that it's becoming a great assay, it's getting to be a lousy test. J Am Coll Cardiol 2010;55:

10 Elevated Troponin in Patients without ACS or Heart Failure Kelley et al. Clin. Chem Dec;55(12): Acute Disease Chronic Disease Cardiac and Vascular Acute Aortic dissection Cerebrovascular accident Ischemic Stroke Intracerebral lhemorrhage Subarachnoid Hemorrhage Medical ICU Patients Gastrointestinal bleeding Respiratory Acute pulmonary embolism ARDS Cardiac Inflammation Endocarditis Myocarditis Pericarditis Muscular Damage Infectious Sepsis Viral Ilness Other Acute Causes of Troponin Elevation Kawasaki kidisease Apical ballooning syndrome TTP Rhabdomyolysis Birth Complications in Infants Extreme Low Birth Weight Heart Specific Preterm Delivery Acute Complications of Inherited Disorders Neurofibromatosis Duchenne Muscular Dystrophy Klippel Feil syndrome Environmental Exposure Carbon Monoxide Hydrogen Sulfide Colchicine exposure ESRD Cardiac infiltrative disorders Amyloidosis Sarcoidosis Hemochromatosis Scleroderma Hypertension Diabetes Hypothyroidism Iatrogenic Invasive Procedures Heart Transplantation Congenital defect repair Radio Frequency Catheter Ablation Lung Resection ERCP Non Invasive Procedures Cardioversion Disease Specific Lithotripsy Pharmacologic sources Chemotherapy Other Medications Myocardial Injury Blunt Chest Injury Endurance athletes Envenomation Snake Jellyfish Spider Centipede Scorpion 10

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12 ROC Area and Time of Symptoms Onset 12

13 ctn at Presentation 13

14 Universal Definition of Myocardial Infarction Joint ESC/ACCF/AHA/WHF Task Force Circulation Nov 27;116(22):

15 Circulation 2011, 124:

16 Circulation 2011, 124:

17 Circulation 2011, 124:

18 Circulation 2011, 124: Absolute ctni Change Relative ctni Change

19 Circulation 2011, 124: Absolute hs-ctnt Change Relativee hs-ctnt Change

20 Circulation 2011, 124:

21 Circulation 2011, 124:

22 Arch Intern Med Sep 10;172(16):

23 30 day outcomes 2 year outcomes 23

24 Population Focus Community Dwelling elderly population p with no incident Heart Failure presenting with no signs, symptoms 24

25 25

26 hstnt and incident HF and Cardiovascular Death Community Dwelling Adults N= years or older Without prior HF hs TnT measurement at baseline Repeat hs TnT measurement 2 3 years later 26

27 <3.00 ng/l >12.94 ng/l Categories 1. < >

28 Summary of population p studies using troponin for risk stratification Troponin Population Outcome Prevalence of ctn Daniels ctnt Older adults + all and CV death 4% Sundstrum ctni Older adults* + HF admission Zelthelius ctni Older adults* + all and CV death NA 8.2% Blankenberg ctni General pop p + CV events Approx 1% defilippi hs ctnt Older adults + HF, + CV death 66% De Lemos hs ctnt General Pop +all-cause death 25% Saunders hs ctnt General Pop + HF, death, CV event Apple hs ctni Older adults + CV death NA Wang hs ctni General pop +HF, death, MACE 67% 28

29 <3.00 ng/l >12.94 ng/l Categories 1. < >

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32 Conclusions: In older adults without HF, baseline ctnt levels and changes in hs TnT levels l over 2 3 years were significantly associated with incident HF and cardiovascular death. 32

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34 Methods Meta analysis of epidemiological studies investigating gphysical activity and primary prevention of CHD. Included prospective cohort studies published in English since Reviewed 3194 study abstracts, included 33 studies in the meta analysis. analysis. Leisure time physical activity (LTPA). 34

35 Spline (smoothed fit) and 95% confidence intervals (CIs) of relative risks of coronary o heart disease levels e of leisure-time e e physical activity ty (LTPA). Individuals who met the basic guideline had a 14% lower risk of CHD than those who engaged in no LTPA Sattelmair J et al. Circulation 2011;124:

36 Spline (smoothed fit) and 95% confidence intervals (CIs) of relative risks of coronary o heart disease levels e of leisure-time e e physical activity ty (LTPA). Those who met advanced guideline had a 20% lower risk of CHD than those who engaged g in no LTPA Sattelmair J et al. Circulation 2011;124:

37 Generalized least squares (GLST) regression spline (smoothed fit) models with 95% confidence intervals (CIs). Sattelmair J et al. Circulation 2011;124: Copyright American Heart Association 37

38 Sattelmair J et al. Circulation 2011;124: Leisure time physical activity 150 min/wk had 14% lower CHD relative risk, 0.86; 95% confidence interval, 0.77 to 0.96, compared with no leisure time physical activity. Conclusions These findings provide quantitative data physical supporting activity had US a 20% physical lower CHD activity guidelines that relative stipulate risk, ik ; some 95% confidence physical interval, activity t i to is better than none and additional benefits occur with more relative risk physical activity. Engaging in the equivalent of 300 min/wk of moderate intensity Higher physical activity levels associated with modestly lower Physically activity at lower levels also had significantly lower CHD. There was a significant interaction by sex (P.0.03); 03); the association was stronger among women than men. 38

39 J Am Coll Cardiol 2012;60: Composite physical activity score: Summed leisure time activity quartiles (range, 1 to 4) and walking pace (range, 1 to 3) to generate a combined with a possible range of 2 to 7. 2 as low activity 3 to 6 as moderate activity 7 as high hactivity i. 39

40 Proportion of patients with a significant Biomarker Increase vs Physical Activity hstnt NTproBNP J Am Coll Cardiol 2012;60:

41 Rate of Incident HF hstnt NTproBNP 41

42 Incidence of New Abnormal Left Ventricular Ejection Fraction (LVEF <55%) in subjects with low baseline biomarker levels based on change Baseline NT-proBNP < 190 pg/ml and ctnt<13 pg/ml N=1322 (65.8%) N=266 (13.2%) N=297 (14.8%) N=123 (6.1%) J Am Coll Cardiol 2012;60:

43 These findings suggest that t moderate physical activity it has protective effects on early heart failure phenotypes, preventing cardiac injuryand neurohormonal activation. J Am Coll Cardiol 2012;60:

44 Randomized Design Hypothesis: At risk subjects with NO EVIDENCE of HF randomized to an exercise regimen will have lower ctn and Natriuretic Peptide values, and fewer adverse events compared to subjects receiving usual care. N=??? At risk subjects with no HF, having Elevated Biomarkers Enrolled Randomize Exercise Regimen Usual Care Data o0llection coo0 Data coollection Outcomes hstn, NT-proBNP Outcomes hstn, NT-proBNP 44

45 Thank You! 45

Cardiac Troponin: Current Status and Future Promise

Cardiac Troponin: Current Status and Future Promise Robert H. Christenson, Ph.D., ABCC, FACB Professor of Pathology Professor of Medical and Research Technology University of Maryland School of Medicine