Peri-operative Troponin Measurements - Pathophysiology and Prognosis

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1 Peri-operative Troponin Measurements - Pathophysiology and Prognosis Allan S. Jaffe, MD.* Consultant - Cardiology & Laboratory Medicine Professor of Medicine Chair, CCLS Division, Department of Laboratory Medicine and Pathology Mayo Clinic and Medical School Rochester, Minnesota *Dr. Jaffe is or has been a consultant to most of the major diagnostic companies and Amgen. CP

2 Elevations of Troponins without Overt Ischemic Heart Disease Trauma (including contusion, ablation, pacing, ICD firings including atrial defibrillators, cardioversion, endomyocardial biopsy, cardiac surgery, after interventional closure of ASDs) Congestive heart failure acute and chronic Aortic valve disease and HOCM with significant LVH Hyper and hypotension, especially with arrhythmias Postoperative noncardiac surgery patients who seem to do well Renal failure Critically ill patients, with respiratory failure, gastrointestinal bleeding, sepsis, heat stroke Drug toxicity, eg adriamycin, 5 FU, herceptin, snake venoms, carbon monoxide poisoning Hypothyroidism Abnormalities in coronary vasomotion, including coronary vasospasm Apical ballooning syndrome Inflammatory diseases eg. myocarditis, eg. Parvovirus B19, Kawasaki disease, sarcoid, smallpox vaccination, or myocardial extension of BE Post PCI patients who appear to be uncomplicated Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, esp if TBSA > 30% Cardiomyopathies including Infiltrative diseases such as amyloidosis, hemachromatosis, sarcoidosis and scleroderma, non compaction syndrome Acute neurological disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy CP Vital Exhaustion

Survival Postop Survival by ctni Values 1.0 0.9 0.

5 and/or 0.03 <ctn-t 0.1 P=0.047 P=0.007 0.6 0.5 0.

3 Survival Postop Survival by ctni Values ctn-i 0.6 and ctn-t < ctn-i 1.5 and/or 0.03 <ctn-t 0.1 P=0.047 P= < ctn-i 3.1 and/ or 0.1 <ctn-t 0.2 ctn-i >3.1 and/or ctn-t >0.2 P< Years after surgery J Am Coll Cardiol 42:1551, 2003 CP CP

Survival Postop Survival by ECG Changes 1.0 0.

5 15 min < ST-dep ischemia 30 min P=0.08 P=0.08 0.4 0.

4 Survival Postop Survival by ECG Changes ST-dep ischemia 15 min min < ST-dep ischemia 30 min P=0.08 P= ST-dep ischemia 30 min J Am Coll Cardiol 42:1551, 2003 Years after surgery CP CP

Association of Longest Ischemia Duration with Biochemical Markers of MI Total No. % No.

9 8 57.1 7 50.0 7 50.0 5 35.7 MB >10% ctn-i >0.6 ng/ml 107 23.9 34 31.8 29 27.1 21 19.6 19 17.

1 ng/ml ctn-i >3.1 ng/ml 21 4.2 19 90.5 17 81.0 17 81.0 13 61.9 and or ctn-t >0.

5 Association of Longest Ischemia Duration with Biochemical Markers of MI Total No. % No. % No. % No. % No. % CK >170 IU and MB >5% CK >170 IU and MB >10% ctn-i >0.6 ng/ml and or ctn-t >0.03 ng/ml ctn-i >1.5 ng/ml and or ctn-t >0.1 ng/ml ctn-i >3.1 ng/ml and or ctn-t >0.2 ng/ml J Am Coll Cardiol 42:1549, 2003 Ischemia >15 min Ischemia >30 min Ischemia >60 min Symptoms attributable to MI CP CP

6 A 67-year-old man - abdominal aortic aneurysm repair Landesberg G et al. Circulation 2009;119: CP

7 Differentiation between MI Types according to the Condition of the Coronary Arteries Plaque rupture with clot MI Type 1 Vasospasm or endothelial dysfunction Fixed Atherosclerosis and Supply-demand imbalance MI Type 2 MI Type 2 Supply-demand imbalance alone MI Type 2 CP

changes, especially ST segment depression More transient ECG changes Out patients

8 CHARACTERISTICS OF TYPE 1 AND TYPE 2 AMIS Type 1 Type 2 Spontaneous around known triggers Higher ctn Some evidence of increased demand Lower ctn Persistent ECG changes, especially ST segment depression More transient ECG changes Out patients Procedure related often More procoagulant activity Procoagulation related inadequate perfusion CP

9 Cumulative hazard ratio Prognosis Over Time After Surgery (POISE) Asymptomatic MI Symptomatic MI Isolated cardiac biomarker or enzyme level elevation Devereaux et al: Ann Intern Med 154:523, 2011 Time after surgery (days) Pt at risk (no.) Symptomatic MI Asymptomatic MI Isolated cardiac biomarker or enzyme level elevation CP

10 Risk (%) Risk (%) Risk (%) Risk (%) Outcomes in POISE 0.08 Primary Outcome (CV Death or Nonfatal AMI or Cardiac Arrest) 0.08 AMI 0.06 Placebo Metoprolol 0.06 Placebo Metoprolol No. at risk No. at risk Placebo 4,177 3,915 3,873 3,854 Placebo 4,177 3,919 3,873 3,859 Metoprolol 4,174 3,958 3,908 3,878 Metoprolol 4,174 3,966 3,917 3, Stroke 0.03 Death Metoprolol Metoprolol Placebo Placebo No. at risk Days No. at risk Days Placebo 4,177 4,105 4,078 4,060 Placebo 4,177 4,119 4,093 4,074 Metoprolol 4,174 4,084 4,038 4,012 Metoprolol 4,174 4,112 4,066 4,039 Lancet 371:1839, 2008 CP

11 Meta-Analysis of -Blocker Trials Relative risk -blocker Control (99% CI) Total mortality Pre-POISE 33/1,080 36/1, ( ) POISE 129/4,174 97/4, ( ) Total 162/5, /5, ( ) P=0.10, I 2 =37% Nonfatal myocardial infarction Pre-POISE 25/958 42/ ( ) POISE 152/4, /4, ( ) Total 177/5, /5, ( ) P<0.0001, I 2 =31% Nonfatal stroke Pre-POISE 12/972 3/ ( ) POISE 27/4,174 14/4, ( ) Total 39/5,146 17/5, ( ) P=0.005, I 2 =0% Relative risk (99% CI) Lancet 371:1839, 2008 CP

12 Survival in Postoperative Patients With and Without Coronary Revascularization Probability of survival No. at risk Coronary artery revascularization No coronary artery revascularization P= Years after randomization Revascularization No revascularization McFalls et al: NEJM 351(27):2795, 2004 CP

13 Patient Flow in the Vision Study 23,693 Patients fulfilled VISION eligibility criteria 1,084 Not identified in time to enroll 22,609 Screened in time 6,522 Excluded 5,262 Did not consent 251 Cognitive impairment 134 Surgeon did not approve 875 Other source 16,087 Enrolled in VISION 954 Excluded from the fourth-generation Troponin T Prognostic Study 779 No troponin assay measured after surgery 29 Died before a troponin assay was measured 750 No troponin assay measured before discharge 146 Had peak troponin measurement reported as <0.04, <0.03, or <0.02 instead of the absolute value 29 Missing data 15,133 Included in the VISION fourth-generation Troponin T Prognostic Study 15,093 Completed the 30-day follow-up 40 Did not complete the 30-day follow-up and were censored at the time of last contact 15,133 Patients included in the final analyses JAMA. 2012;307(21): CP

Cumulative hazard Mortality Analysis by Peak ctnt Value (VISION) Peak troponin T (ng/ml) 0.30 0.03-0.29 0.02 0.01 Days after surgery No. at risk Peak troponin T (ng/ml) 0.

14 Cumulative hazard Mortality Analysis by Peak ctnt Value (VISION) Peak troponin T (ng/ml) Days after surgery No. at risk Peak troponin T (ng/ml) ,376 13,348 13,300 13,271 13,250 12,230 13,209 JAMA. 2012;307(21): CP

15 Relationship of -Blockers and 30-Day Mortality All surgery No. of patients No. of deaths Exposed Not exposed Exposed Not exposed All patients 37,805 37, Revised cardiac risk index predictors (no.) 0 12,250 12, ,057 16, ,795 6, ,090 2, > Favors exposure Favors nonexposure Vascular surgery No. of patients No. of deaths Exposed Not exposed Exposed Not exposed All patients 3,999 3, Revised cardiac risk index predictors (no.) ,593 1, ,033 1, > Relative risk (95% CI) Favors exposure Favors nonexposure London et al: JAMA 309(16):1704, Relative risk (95% CI) CP

16 Relationship of -Blockers and 30-Day Cardiac Morbidity All surgery No. of patients No. of deaths Exposed Not exposed Exposed Not exposed All patients 37,662 37, Revised cardiac risk index predictors (no.) 0 12,228 12, ,004 16, ,761 6, ,063 2, > Favors exposure Favors nonexposure Vascular surgery No. of patients No. of deaths Exposed Not exposed Exposed Not exposed Favors exposure All patients 3,973 3, Revised cardiac risk index predictors (no.) ,590 1, ,024 1, > London et al: JAMA 309(16):1704, Relative risk (95% CI) Favors nonexposure Relative risk (95% CI) CP

17 Survival Cumulative Survival (A= Stress testing, B = Angiography) 1.0 Group B (n=105) Group A (n=103) P=0.01 Group A n= Group B n= Years from randomization JACC 54(11):989, 2009 CP

18 Freedom from MACE Freedom from Major Adverse Cardiac Events (A= Stress testing, B = Angiography) Group B (n=105) Group A (n=103) P=0.003 Group A n= Group B n= Years from randomization JACC 54(11):989, 2009 CP

19 Frequency (%) Distribution of Preoperative hsc-tnt Values in Vision Published 99 th 14 ng/l VISION 95 th 33 ng/l VISION 99 th >72 ng/l TnT-hs (ng/l) Kavsak et al: Clin Biochem 44:1021, 2011 CP

20 Frequency (%) 50 Frequency of Elevated hsc-tnt Postoperative Values Published 99 th TnT hs VISION 95 th TnT hs VISION 99 th TnT hs >85% change in TnT hs from preop >242% change in TnT hs from preop TnT 4 th gen >0.03 g/l 0 Day 1 Day 2 Day 3 Postoperative days Kavsak et al: Clin Biochem 44:1021, 2011 CP

21 Preoperative hsctnt and Myocardial Infarction Myocardial infarction Postop Troponin I elevation >0.07 g/l % <14 ng/l >14 ng/l Preoperative hs-ctnt concentration AHJ, 2013, (in press) CP

22 All-cause mortality (%) All-Cause Mortality based on Preopeartive hsctnt >14 ng/l <14 ng/l Survival time (years) AHJ, 2013, (in press) CP

23 All-cause mortality (%) All-cause mortality (%) All-Cause Mortality based on Sex-Specific 99 th Percentiles for Preoperative hsctnt Women >10 ng/l Men >15 ng/l <10 ng/l <15 ng/l Survival time (years) Survival time (years) AHJ, 2013, (in press) CP

24 All-cause mortality (%) All-Cause Mortality Grouped by Preoperative hsctnt Quartiles Quartile (ng/l) 4 (>19.3) 3 ( ) 1 (<8.3) 2 ( ) Survival time (years) AHJ, 2013, (in press) CP

25 Mortality (%) Predictive Accuracy of Biomarkers to Presage Mortality 8 P< P= P= <300 pg/ml 300 pg/ml 14 ng/l >14 ng/l n=644 n=355 n=746 n=233 n=277 n=450 n=187 n=65 NT-proBNP hs-tnt Lee index Weber et al: Eur Heart J 34:853, 2013 CP

26 Combined endpoint (%) Combining Lee Index and hsctnt to Predict CV Events hs-tnt 14 ng/l hs-tnt >14 ng/l Lee score = 0 Lee score = 1 Lee score > 2 n=243 n=34 n=352 n=98 n=151 n=101 Weber et al: Eur Heart J 34:853, 2013 CP

27 Mortality (%) Combining Lee Index and hsctnt to Predict Mortality 10 8 hs-tnt 14 ng/l hs-tnt >14 ng/l Lee score = 0 Lee score = 1 Lee score > 2 n=243 n=34 n=352 n=98 n=151 n=101 Weber et al: Eur Heart J 34:853, 2013 CP

28 Comparative Incidence of Plaque Rupture Author Postop cases Cohen Dawood et al Combined Non-postop cases Constantanides Hori et al Quiao et al Burke et al Combined Point estimate with 95% CI 46% 36% 49% % 50% 51% 55% 64% Cohen and Aretz: Cardiovasc Pathol 8(3):133, % CP

29 Angiographic Characteristics PACS no. (%) SACS no. (%) Stable CAD no. (%) P Complex lesion 68 (56.7) 95 (79.2) 76 (31.8) <0.001 Ambrose s type II lesions 54 (45.0) 68 (56.7) 44 (16.4) <0.001 Thrombus 9 (7.5) 39 (32.5) 21 (8.8) <0.001 Ulceration 15 (12.5) 18 (15.0) 16 (6.7) 0.03 Haziness 45 (37.5) 54 (45.0) 39 (16.3) <0.001 TIMI flow <3 27 (22.5) 61 (50.8) 48 (20.1) <0.001 Gualandro DM et al: Atherosclerosis, 2012 (in press) CP

Does serial troponin measurement help identify acute ischemia/ischemic events?

Does serial troponin measurement help identify acute ischemia/ischemic events? Allan S. Jaffe, MD.* Consultant - Cardiology & Laboratory Medicine Professor of Medicine and Laboratory Medicine & Pathology