TROPONINS HAVE THEY CHANGED YOUR

Transcription

1 TROPONINS HAVE THEY CHANGED YOUR PRACTICE THIS WEEK? Harvey White John Neutze Scholar Green Lane Cardiovascular Service and Cardiovascular Research Unit Auckland City Hospital, Auckland, New Zealand

2 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the healthcare related company listed below Financial Relationship Research Grants Consulting Company Sanofi Aventis; Eli Lilly; NIH; Merck Sharpe & Dohme; AstraZeneca; GSK; Daiichi Sankyo Pharma Development AstraZeneca

3 Cardiac Markers The Troponins Troponin Complex TnT Actin TnC TnI Tropomyosin

4 Elevated Troponins Any elevation, in no matter what setting, denotes a worse prognosis

5 Utility of hs troponins in ACS White HD. In: Advances in acute coronary syndromes management. Ed: White HD. Biomarkers in acute coronary syndromes. Future Medicine; p

6 Introduction of high sensitivity Troponins Implications for assessment of chest pain Earlier rule out Earlier diagnosis (rule in) Improved risk stratification Earlier and higher institution of evidence based therapy Likely reduced costs Increase in the number of MIs with a resultant decrease in the number of patients with unstable angina

7 Cardiac procedure Myocardial Injury Myocardial injury with cell death marked by cardiac troponin elevation Non-cardiac major procedure Tachy-/bradyarrhythmia Myocardial Infarction MIM Clinical evidence of acute myocardial ischemia with rise and/or fall of cardiac troponin Heart failure Renal failure Thygesen, Alpert, White. Universal Definition of Myocardial Infarction 2012

8 Biomarkers for chest pain assessment Even small concentrations of troponin in the context of ACS or in community populations predict a higher risk for CHD events Consensus statements recommend use of the 99 th percentile for a normal population as the upper reference limit for troponin assays with a CV of 10% In the absence of ACS, very low cardiac troponin values are expected and therefore it is critical that we evaluate changes in levels to distinguish acute from chronic conditions

9 What is the evidence about low troponin levels?

10 What is the evidence about low troponin levels? Evidence with very low levels of contemporary troponins Epidemiology Heart failure Coronary artery disease Atrial fibrillation Diabetes MI and unstable angina

11 Evidence with very low levels of contemporary troponins

12 (%) Troponin T: 1 o EP at 6 months Death, MI, Rehosp ACS CONS p=ns INV 24.2 * OR=0.52 (0.38,0.73) *p< Interaction p< N= TnT - TnT + TnT cut point = 0.01 ng/ml (54% of Pts TnT +)

13 High sensitivity troponins and the community

14 Dallas Heart Study, all-cause mortality de Lemos et al. JAMA 2010;304:

15 High sensitivity troponins and Heart Failure

16 Troponin T in chronic heart failure Elevated TnT (4 th generation) in 10.4% of patients in VAL-HeFT with chronic heart failure ( 0.01ug/mL) hstnt ( 0.001ug/ml) detectable in 92% of patients Patients with elevated TnT had more severe heart failure and were more likely to be older, have diabetes, AF, and higher creatinine levels Latini Circ 2007; 116: 1242

17 Mortality % VAL-HeFT : 2 year mortality according to BNP and hstnt % % 19.9% % 0 BNP <median hstnt <median BNP >median hstnt <median BNP <median hstnt >median BNP >median hstnt >median BNP (93pg/mL) hstnt (0.0124ng/mL) Latini Circ 2007; 116: 1242

18 High sensitivity troponins and coronary artery disease

19 PEACE hstnt detected (1ng/L) in 97% of 3679 patients with stable CAD 11.1% of patients had levels 14ng/L Levels were associated with diabetes and hscrp Strong and graded relationship with cardiovascular death and heart failure on follow up to 5.2 years No relationship with MI

20 % Distribution patterns of hs-tni (architect stat) and hs-tnt in stable CAD <1 [1;3] [3;5] [5;7] [7;9] [9;11] [11;13] [13;15] [15;17] [17;19] [19;21] 21 pg/ml hs-tnl hs-tnt Omland T et. al. JACC. 2013; Epub ahead of print.

21 Cardiovascular death or heart failure (%) Risk for cardiovascular death or heart 15 failure by baseline hs-tni level 10 Quartile 1 Quartile 2 Quartile 3 Quartile 4 5 p< Years Omland T et. al. JACC. 2013; Epub ahead of print.

22 Troponins in atrial fibrillation

23 Myocardial Infarction: RE-LY Troponin I was measured with the high sensitivity Beckman Access Accu assay which is not available for commercial use There were 103 myocardial infarctions The annual rates were 0.49% in the group with undetectable troponin I and 1.69% (HR 3.04; 95% CI ) in the highest troponin I group, p= The association of troponin I and myocardial infarctions remained significant after adding NT-proBNP to the model There was no significant relation between NT-proBNP levels and myocardial infarction Hijazi, Z., et al. Circulation. 2012; 125:1605

24 Troponin I and risk for stroke or systemic embolism: RE-LY Hijazi, Z., et al. Circulation. 2012; 125:1605

25 Troponin I and vascular death: RE-LY Hijazi, Z., et al. Circulation. 2012; 125:1605

26 Troponin I and stroke, systemic embolism, pulmonary embolism, myocardial infarction, vascular death: RE-LY Hijazi, Z., et al. Circulation. 2012; 125:1605

27 Troponin I in relation to major bleeding: RE-LY Biomarkers Group Total number of events, n (%/y) HR (95% CI) P value effect of biomarker level Troponin I group (µg/l) < (1.72) (2.94) 1.48 ( ) (3.25) 1.50 ( ) (4.38) 2.01 ( ) Hijazi, Z., et al. Circulation. 2012; 125:1605

28 High sensitivity troponins in diabetes

29 Percentage of subjects with elevated high sensitivty TnT by HbA1c category NZ Rubin, J., et al. JACC. 2012; 59:484

30 Chronic hyperglycaemia and subclinical myocardial injury Higher HbA1c is associated with elevated high sensitivity troponin T among patients without clinically evident CHD, suggesting that hyperglycemia contributes to myocardial injury beyond its effects on development of clinical atherosclerotic coronary disease And may be a marker of an intermediate cardiovascular phenotype on the pathway to heart failure Rubin, J., et al. JACC. 2012; 59:484

31 There is confusion as to what is a high sensitivity assay

32 Implications of having non- guideline compliant Troponins Misdiagnosis Mistreatment: lack of evidence based treatments and application inappropriately; risks of angiography, side effects of therapies Inappropriate advice about driving, returning to work, insurability etc Increased costs

33 Biomarkers for chest pain assessment Cardiologists want to rule in ED Physicians want to rule out

34 Elevations of cardiac troponin values because of myocardial injury Injury related to primary myocardial ischemia (MI type 1) Injury related to supply/demand imbalance of myocardial ischemia (MI type 2) Injury not related to myocardial ischemia Multifactorial or indeterminate myocardial injury Thygesen, Alpert, White. Universal Definition of Myocardial Infarction 2012

35 Elevations of cardiac troponin values because of myocardial injury Criteria for acute myocardial infarction Plaque rupture Intraluminal coronary artery thrombus formation Thygesen, Alpert, White. Universal Definition of Myocardial Infarction 2012

36 Elevations of cardiac troponin values because of myocardial injury Injury related to supply/demand imbalance of myocardial ischaemia Tachy-/brady-arrhythmias Aortic dissection or severe aortic valve disease Hypertrophic cardiomyopathy Cardiogenic, hypovolaemic or septic shock Severe respiratory failure Severe anaemia Hypertension with or without LVH Coronary spasm Coronary embolism or vasculitis Coronary endothelial dysfunction without significant CAD Thygesen, Alpert, White. Universal Definition of Myocardial Infarction 2012

37 Elevations of cardiac troponin values because of myocardial injury Injury not related to myocardial ischaemia Cardiac contusion, surgery, ablation, pacing or defibrillator shocks Rhabdomyolysis with cardiac involvement Myocarditis Cardiotoxic agents, e.g., anthracyclines, herceptin Thygesen, Alpert, White. Universal Definition of Myocardial Infarction 2012

38 Elevations of cardiac troponin values because of myocardial injury Multifactorial or indeterminate myocardial injury Heart failure Stress (Takotsubo) cardiomyopathy Severe pulmonary embolism or pulmonary hypertension Sepsis and critically ill patients Renal failure Severe acute neurological diseases, e.g., stroke, subarachnoid haemorrhage Infiltrative diseases, e.g., amyloidosis, sarcoidosis Strenuous exercise Thygesen, Alpert, White. Universal Definition of Myocardial Infarction 2012

39 Dealing with high sensitivity Troponin elevations in clinical practice

40 Receiver operating characteristic curves showing the diagnostic performance for the diagnosis of acute myocardial infarction provided by absolute ( ) and relative ( %) changes 1hr Reichlin; N Engl J Med 2009;361:858

41 New Zealand 2012 Guidelines for the Management of Non ST-Elevation Acute Coronary Syndromes Use of hstnt to diagnose myocardial infarction in a clinical setting consistent with myocardial ischemia Baseline 14 ng/l ng/l 50 ng/l Retest hstnt 3 hours later Change <50% Retest hstnt 3 hours later Change 50% Change <20% Retest hstnt 3 hours later Change 20% 14 ng/l rules out MI with >90% probability If 15 ng/l then proceed to middle part of algorithm Adverse prognosis Retest hstnt at 6, 12 hr Myocardial infarction Evidence based treatments

42 Survival free from death or recurrent MI in patients with suspected ACS before (validation phase) and after (implementation phase) of a sensitive troponin I assay 79% p= % Mills, N L. et al. JAMA 2011;305:

43 TROPONINS HAVE THEY CHANGED YOUR PRACTICE THIS WEEK? Harvey White John Neutze Scholar Green Lane Cardiovascular Service and Cardiovascular Research Unit Auckland City Hospital, Auckland, New Zealand

44 Chronic hyperglycaemia and subclinical myocardial injury

45 Chronic hyperglycaemia and subclinical myocardial injury Analysis of the association between baseline HbA1c and high-sensitivity troponin T in 9,661 participants free of CHD and heart failure in the ARIC (Atherosclerosis Risk in Communities) study Multivariable logistic regression models characterized the association between clinical categories of HbA1c (<5.7%, 5.7% to 6.4%, and 6.5%) and primary outcome of high sensitivity troponin T 14ng/L Rubin, J., et al. JACC. 2012; 59:484

46 Chronic hyperglycaemia and subclinical myocardial injury Higher values of HbA1c were associated in a graded fashion with elevated high sensitivity troponin T, p<0.001 After adjusting for traditional risk factors, compared to patients with HbA1c <5.7%, the odds ratios of elevated high sensitivity troponin T for persons with HbA1c 5.7% to 6.4% and 6.5% were 1.26 ( ) and 1.97 ( ) Rubin, J., et al. JACC. 2012; 59:484

47 High sensitivity troponins in renal failure

48 Use of high sensitivity troponin T to diagnose myocardial infarction Clinical setting consistent with myocardial ischemia Baseline 14 ng/l Retest hstnt 3 hours after symptom onset or if timing of symptom onset is unclear at 3 hours after presentation Change <50% 15 - <50 ng/l Retest hstnt 3 hours later Change 50% 50 ng/l Retest hstnt 3 hours later Change <20% Change 20% 14ng/L rules out MI with >90% probability If 15ng/L then proceed to middle part of algorithm. Adverse Prognosis Retest hstnt at 6,12 hr Evidence based treatments Myocardial infarction White HD; AHJ. 2010; 159: 932

49 Higher sensitivity troponins and higher use of evidence based medicine and better outcomes

50 Progression of Atherosclerosis and Troponin values Minimal or no disease: troponin detectable with hstroponins Significant structural disease troponin higher than 99 th % ACS and other acute situations - rising troponin values Superficial Erosion Ruptured Fibrous Cap Modified from Libby P., et al. Circulation. 2001; 104: 365