Post Operative Troponin Leak: David Smyth Christchurch New Zealand

Transcription

1 Post Operative Troponin Leak: Does It Really Matter? David Smyth Christchurch New Zealand

2 Life Was Simple Once Transmural Infarction Subendocardial Infarction

3 But the Blood Tests Were n t Perfect Creatine Kinase Heart and Skeletal Muscle Aspartate Transaminase Heart and Liver Lactate Dehydrogenase Heart, Brain, Red Cell

4 Cardiac Troponins (ctn) Structural Proteins of the Contractile Apparatus of Skeletal and Myocardial Myocytes. Three subunits: T (TnT), I (TnI), and C (TnC). Skeletal and Cardiac Myocyte Isoforms of TnI and TnT are different Allows for high specificity in the measurement of the cardiac forms (the cardiac troponins, ctn). High sensitivity Tests Have Been Introduced into Clinical Practice

5 Cardiac Troponins (ctn) as Biomarkers Biphasic Release Kinetics Following Injury Initially Myocardial Cell Damage Releases Unbound Cytosolic ctn Detectable 4-6h After Insult Peaks at 12-24h Structural Proteins Released 2-4 Days After Injury Continuing Breakdown of Myofibrillary-Bound Complex Persists for up to 14 days after Injury CK-MB Better to Diagnose Recurrent Injury (infarction) However detectable increases ctn Indicate Myocardial Injury Do Not Imply Mechanism of Injury Can Not (in isolation) be used to Diagnose Acute Myocardial Infarction

6 Release Kinetics of Myocardial Injury Markers

7 Post Operative Cardiac Mortality 1977 Goldman Risk Evaluation System (1001 Patients Undergoing Surgery) 22% rate of life-threatening cardiovascular events >50% mortality in the highest-risk group 2011 Finks et al. 2.8% National Mortality Rate for Open Abdominal Aortic Aneurysm repair Fall in Mortality is Incremental: Advances in Anaesthetic Technique Surgical Technique Perioperative Medical Treatment Could High ctn Monitoring Help Reduce it Further? Goldman et al. N Engl J Med. 1977;297: Finks et al. N Engl J Med. 2011;364:

8 Revised Definition of MI from the European Society of Cardiology/American College of Cardiology One of the following: Increase and/or decrease of biochemical markers of myocardial necrosis Troponin Creatine kinase MB isoenzyme Plus at least one of the following: Ischaemic symptoms Development of pathological Q waves on the ECG ECG changes indicative of ischaemia Acute Coronary Stenosis / Occlusion at Angiography Pathological findings of Acute MI Five Main Groups of Myocardial Infarction Type 1: infarction Spontaneous myocardial Type 2: Myocardial infarction secondary to an ischaemic imbalance Type 3: Myocardial infarction resulting in death when biomarker values are unavailable Type 4a: Myocardial infarction related to percutaneous coronary intervention (PCI) Type 4b: Myocardial infarction related to stent thrombosis Type 5: Myocardial infarction related to coronary artery bypass grafting (CABG) Alpert et al. J Am Coll Cardiol 2000; 36:

9 Why Might Surgery Cause Increased ctn? It May Already Be Raised Stress of Surgery May Rupture Plaque and Cause Acute Infarction Supply-Demand Imbalance: Transient AF / Perioperative Hypotension Something Else Pulmonary Embolism Myo-Pericarditis Multi-Organ Inflammatory State Sepsis

10 Why Might Surgery Cause Increased ctn? It May Already Be Raised Stress of Surgery May Rupture Plaque and Cause Acute Infarction Supply-Demand Imbalance: Transient AF / Perioperative Hypotension Something Else Pulmonary Embolism Myo-Pericarditis Multi-Organ Inflammatory State Sepsis

11 Dallas Heart Study: HScTnT in Healthy Individuals ctnt Measured in 3546 Individuals aged 30 to 65 years between 2000 and 2002 in Dallas County Prevalence of Detectable HScTnT (0.003ng/mL) was 25.0% de Lemos et al. JAMA. 2010;304(22):

12 Dallas Heart Study: HScTnT in Healthy Individuals ctnt Measured in 3546 Individuals aged 30 to 65 years between 2000 and 2002 in Dallas County Prevalence of Detectable HScTnT (0.003ng/mL) was 25.0% de Lemos et al. JAMA. 2010;304(22):

13 patients The Vascular Events In Non Cardiac Surgery (VISION) Study TnT levels were Measured 6-12h Post Surgery Repeated on days 1, 2, and 3 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%) Conclusion Among Patients Undergoing Non Cardiac Surgery, Peak Postoperative TnT in the First 3 days after Surgery was Significantly Associated with 30-Day Mortality VISION Study Investigators JAMA. 2012;307:

14 VISION Study Investigators JAMA. 2012;307: VISION Study: Predictors of Cardiac and Non Cardiac Risk

15 Why Might Surgery Cause Increased ctn? It May Already Be Raised Stress of Surgery May Rupture Plaque and Cause Acute Infarction Supply-Demand Imbalance: Transient AF / Perioperative Hypotension Something Else Pulmonary Embolism Myo-Pericarditis Multi-Organ Inflammatory State Sepsis

16 Will β-blockers Help?: The POISE Trial Primary End Point: Cardiac Death, MI, Stroke 8351 Patients With or at Risk of Atherosclerosis Disease Undergoing Non-Cardiac Surgery Metoprolol (n=4174) or placebo (n=4177) Started 2 4 h before surgery and continued for 30 days p= % 5 8% Devereaux et al. Lancet 2008; 371:

17 Will β-blockers Help?: The POISE Trial MI 8351 Patients With or at Risk of Atherosclerosis Disease Undergoing Non-Cardiac Surgery Metoprolol (n=4174) or placebo (n=4177) Started 2 4 h before surgery and continued for 30 days p= % 4.2% Devereaux et al. Lancet 2008; 371:

18 Will β-blockers Help?: The POISE Trial Stroke 8351 Patients With or at Risk of Atherosclerosis Disease Undergoing Non-Cardiac Surgery Metoprolol (n=4174) or placebo (n=4177) Started 2 4 h before surgery and continued for 30 days p= % 0.5% Devereaux et al. Lancet 2008; 371:

19 Will β-blockers Help?: The POISE Trial Total Death 8351 Patients With or at Risk of Atherosclerosis Disease Undergoing Non-Cardiac Surgery Metoprolol (n=4174) or placebo (n=4177) Started 2 4 h before surgery and continued for 30 days p= % 2.3% Devereaux et al. Lancet 2008; 371:

20 Criticisms of POISE Iranian Hospitals Aggressive β-blockade Metoprolol 200mg/Day HR 55 Systolic BP 100mmHg Aggrevate Effects of Post Operative Sepsis For Every 1000 Treated, Extended Release Metoprolol Resulted in an Excess of: 8 deaths 5 Patients With a Stroke 53 Clinically Significant Hypotension 42 Clinically significant bradycardia Devereaux et al. Lancet 2008; 371:

21 What About Aspirin? POISE 2 10,010 Patients Undergoing Non Cardiac surgery With Increased Risk of Vascular Complications Primary Endpoint 2x2 Randomised Trial: Aspirin+/- Clonidine+/- Placebo No PreExisting Aspirin Therapy Initiation Stratum: 5628 patients Chronic Aspirin Therapy Continuation stratum: 4382 Patients Started Immediately Pre Operatively (200mg) Continued for 30 Days (100mg) Primary Outcome Composite of Death or Nonfatal Myocardial Infarction at 30 days Devereaux et al. N Engl J Med 2014;370:

22 What About Aspirin? POISE 2 10,010 Patients Undergoing Non Cardiac surgery With Increased Risk of Vascular Complications 2x2 Randomised Trial: Aspirin+/- Clonidine+/- Placebo No PreExisting Aspirin Therapy Initiation Stratum: 5628 patients Chronic Aspirin Therapy Continuation stratum: 4382 Patients Started Immediately Pre Operatively (200mg) Continued for 30 Days (100mg) Primary Outcome Composite of Death or Nonfatal Myocardial Infarction at 30 days Devereaux et al. N Engl J Med 2014;370:

23 What About Aspirin? POISE 2 Major Bleeding 10,010 Patients Undergoing Non Cardiac surgery With Increased Risk of Vascular Complications 2x2 Randomised Trial: Aspirin+/- Clonidine+/- Placebo No PreExisting Aspirin Therapy Initiation Stratum: 5628 patients Chronic Aspirin Therapy Continuation stratum: 4382 Patients Started Immediately Pre Operatively (200mg) Continued for 30 Days (100mg) Increased Risk Of Bleeding Primary Outcome Composite of Death or Nonfatal Myocardial Infarction at 30 days Devereaux et al. N Engl J Med 2014;370:

24 Why Might Surgery Cause Increased ctn? It May Already Be Raised Stress of Surgery May Rupture Plaque and Cause Acute Infarction Supply-Demand Imbalance: Transient AF / Perioperative Hypotension Something Else Pulmonary Embolism Myo-Pericarditis Multi-Organ Inflammatory State Sepsis

25 What About Clonidine? POISE 2 10,010 Patients Undergoing Non Cardiac surgery With Increased Risk of Vascular Complications 2x2 Randomised Trial: Aspirin+/- Clonidine+/- Placebo Clonidine Started Immediately Pre Operatively (0.2mg) Continued for 72h Primary Outcome Composite of Death or Nonfatal Myocardial Infarction at 30 days Primary Endpoint Devereaux et al. N Engl J Med 2014;370:

26 What About Clonidine? POISE 2 10,010 Patients Undergoing Non Cardiac surgery With Increased Risk of Vascular Complications 2x2 Randomised Trial: Aspirin+/- Clonidine+/- Placebo Clonidine Started Immediately Pre Operatively (0.2mg) Continued for 72h Primary Outcome Composite of Death or Nonfatal Myocardial Infarction at 30 days Devereaux et al. N Engl J Med 2014;370:

27 Conundra Who Should Be Targeted? Everyone Only Those at High risk What Should We Do About It? Are There Harmful Consequences In Some?

28 VISION Study Investigators JAMA. 2012;307: VISION Study: Predictors of Cardiac and Non Cardiac Risk

29 VISION Study: Predictors of Cardiac and Non Cardiac Risk Age VISION Study Investigators JAMA. 2012;307:

30 VISION Study: Predictors of Cardiac and Non Cardiac Risk Age VISION Study Investigators JAMA. 2012;307:

31 VISION Study: Predictors of Cardiac and Non Cardiac Risk Risks VISION Study Investigators JAMA. 2012;307:

32 VISION Study: Predictors of Cardiac and Non Cardiac Risk Risks VISION Study Investigators JAMA. 2012;307:

33 VISION Study: Predictors of Cardiac and Non Cardiac Risk Surgery VISION Study Investigators JAMA. 2012;307:

34 VISION Study: Predictors of Cardiac and Non Cardiac Risk Surgery VISION Study Investigators JAMA. 2012;307:

35 VISION Study: Predictors of Cardiac and Non Cardiac Risk ctn VISION Study Investigators JAMA. 2012;307:

36 VISION Study: Predictors of Cardiac and Non Cardiac Risk ctn VISION Study Investigators JAMA. 2012;307:

37 Will Revascularisation Help? BARI 2D: Troponin Substudy 2368 Patients Who Had Both Type 2 Diabetes and Stable Ischaemic Heart Disease with Mild/No Symptoms Randomised to either Prompt Revascularisation (PCI or CABG) vs Optimal Medical Therapy Troponin T Measured at Baseline 2277 (99.6%) had detectable ( 3 ng/l) troponin T concentrations 897 (39.3%) had abnormal troponin T concentrations at baseline ( 14 ng/l) Primary Endpoint: Cardiac Death, Stroke, MI Everett et al. N Engl J Med 2015;373:610-20

38 Will Revascularisation Help? BARI 2D: Troponin Substudy 2368 Patients Who Had Both Type 2 Diabetes and Stable Ischaemic Heart Disease with Mild/No Symptoms Randomised to either Prompt Revascularisation (PCI or CABG) vs Optimal Medical Therapy Troponin T Measured at Baseline 2277 (99.6%) had detectable ( 3 ng/l) troponin T concentrations 897 (39.3%) had abnormal troponin T concentrations at baseline ( 14 ng/l) All Cause Mortality Everett et al. N Engl J Med 2015;373:610-20

39 How To Deal With an Elevated Post Operative ctn Start Early: Check Pre Surgery ctn >65 Major Surgery Neurosurgery Stratify Risk with Worst case Scenario DES Ensure Patients with High Cardiovascular Risk are on appropriate Therapy Statins Β Blockers (?) Post Op?Clinical Evidence of Acute Myocardial Infarction Symptoms (?) ECG Consider Echo Wall Motion Abnormality Overall LV Function If Abnormal: Consider Angiography and Revascularisation if Appropriate Low Dose Aspirin (?)