Troponisms, necrosettes, enzyme leaks, enzyme bumps, infarctlets, minor myocardial damage

1. Troponisms, necrosettes, enzyme leaks, enzyme bumps, infarctlets, minor myocardial damage What’s behind this new lexicon and what does it add? D.R. Holmes jr; P.B. Berger Circulation 2001; 104:627

2. Why a new definition of MI? • To search for a common way of referring a diagnosis • Changes in the enviroment (PCI, mega trials, insurance) require a more precise definition of MI • Changes in technology (biomarkers, imaging) need reevaluation of established definitions of MI • Any amount of myocardial damage, as detected by cardiac troponins, implies an impaired clinical outcome for the patient

3. THE NEW DEFINITION OF MI • Anyone of the following criteria satisfies the • diagnosis of acute, evolving, or recent MI • Typical rise (troponin) or rise and fall (CKMB) of biomarker of myocardial necrosis with at least 1 of the following • Ischemic symptoms • Pathological Q waves on the ECG • ST elevation or depression on the ECG • Coronary artery intervention

4. The new definition of MI: the impact on: • Cardiologist • Pathologist • Biochemist • Epidemiologist • Trialist • Public policy

5. THE CONSENSUS DOCUMENT ON MI REDIFINITION: CLINICAL ISSUES I • Increases of cardiac Tn are indicative of myocardial injury but are not synonymous with MI or an ischemic mechanisms of injury. Therefore, increases in Tn does not mandate a diagnosis of MI • Increases in cardiac Tn likely reflect irreversible rather than reversible injury • The degree of increase of cardiac Tn in ischemia- induced injury is related to the patient’s prognosis

6. INTERPRETATION OF INCREASED BIOMARKERS OF MYOCARDIAL INJURY THE NEW PARADIGM The powerful prognostic impact of modest and sustained increases of Troponins in blood implies that they are more sensitive markers of myocardial necrosis AN ALTERNATIVE INTERPRETATION Persistent, modest elevations of Troponins may reflect important pathogenetic processes (recurrent ischemic episodes with stunning, inflammation...) contributing to an adverse prognosis in patients with CAD that constitute attractive targets for therapeutic intervention

7. Interpretation of true mild elevations of troponin and absent elevations of CK THE NEW PARADIGM AN ALTERNATIVE INTERPRETATION Plaque disruption Extent and instability of CAD Embolization Inflammatory response Microvascular obstruction Proteolyisis Myocardial damage Elevation of Tn Elevation of Tn

8. THE CONSENSUS DOCUMENT ON MI REDIFINITION: CLINICAL ISSUES II • The new criteria require only a maximum concentration of Troponin T or I exceeding the decision limit (99th percentile of the values for a reference control group) on at least one occasion during the first 24 hrs after the index clinical event (Table 2 Consensus Document) • There are circumstances in which is not possible to show infarct-related rises and falls in troponin or CK-MB • For abnormal troponin or CK-MB to be an absolute requirement for the diagnosis of nonfatal acute MI seems inappropriate. The reliability of diagnosis based on evaluation of classic ECG changes alone is high

9. THE CONSENSUS DOCUMENT ON MI REDIFINITION: CLINICAL ISSUES III • A congrous number of patients, formerly diagnosed as having unstable angina, are now redifined as having an acute myocardial infarction. • However, the management of such patients differs from that of those with a completed infarction • The new criteria may also select for a clinically less complicated patient population with MI

10. THE CONSENSUS DOCUMENT ON MI REDIFINITION: CLINICAL ISSUES IV • Patients who undergo PCI are likely to have increased cardiac troponin as a consequence of the procedure. It is indicative of ischemic cell death and should be labeled as MI • Interventional cardiologists and cardiac surgeons will not be pleased to have to tell postoperative patients with a trivial rise in troponins that they had a myocardial infarction • Although it seems obvious that no biomarkers elevation can possibly be good for patients, it is not at all clear that all such elevations are measurably bad for patients either. • Whether small degrees of cardiac enzyme and biomarker elevations after otherwise uncomplicated procedures have any impact on survival requires huge number of patients and long-term follow-up

11. Our hospital are plagued by troponin mildly elevated while CK is within mormal values Bruce Graham

12. CAUSES OF TROPONINOSIS • Analytic and and clinical performance characteristics of the various commercial assays available Up to a 20-fold variation in serum cardiac Tn I concentration may be observed for a given patient sample with different analytic methods (Wu AHB et al. Clin Chem 1998; 44: 1198) • Cross-reactivity with other components in the blood • Antibody interference

13. Troponin elevation independently of myocardial ischemia • Increased preload • Chronic heart failure • Chronic renal insufficiency • Pulmonary embolism • Hypertension, myocardial hypertrophy • Arrhythmias • Sepsis • Myocarditis • Chemiotherapy

14. Preload-induced Troponin I Elevation Independently of Myocardial Ischemia Increased Preload Mechanical strains Myocyte calcium entry Activation of -calpains TnI proteolyisis Feng J et al. Circulation 2001; 103:2035

15. MITIGATING TROPONINOSIS • Standardization and calibration of Tn assays • Reference values must be determined in each lab • True elevations of Tn I are often accompanied by proportional elevation in CK-MB and ECG changes • True elevations of Tn I at the lower end of analytic sensitivity without CK-MB elevations (minor myoc. damage) are characterized by continued or rising elevations of Tn I • Look at the appropriate clinical setting • Use in diagnosis further qualifications and descriptors