Post-Procedural Myocardial Injury or Infarction

Transcription

1 Post-Procedural Myocardial Injury or Infarction Hugo A Katus MD & Evangelos Giannitsis MD Abteilung Innere Medizin III Kardiologie, Angiologie, Pulmologie Universitätsklinikum Heidelberg Conflict of Interest: Prof. Katus has invented the troponin T assay and holds a patent jointly with Roche

2 Universal Definition of Myocardial Infarction: Sub-Classification of AMI Type 1 Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as plaque erosion or rupture, fissuring or dissection Type 2 Type 3 Myocardial infarction secondary to ischemia due to imbalance between oxygen demand and supply e.g. coronary spasm, anemia, or hypotension Sudden cardiac death with symptoms of ischemia, accompanied by new ST elevation or LBBB, or verified coronary thrombus by angiography or autopsy, but death occurring before blood samples could be obtained Type 4a Myocardial infarction associated with PCI Type 4b Myocardial infarction associated with verified stent thrombosis Type 5 Myocardial infarction associated with CABG

3 Joint ESC/ACCF/AHA/WHF Task Force: Universal Definition of MI Type 4a In the setting of percutaneous coronary artery interventions, small infarcts may, and should, be detected by serial blood sampling and analysis before and after the procedure (6 to 8 h and 24 h, respectively). The peak level of the myocardial biomarkers may be pronounced and of relatively greater magnitude because of the reperfusion associated with the procedure. Thygesen K, et al. Eur Heart J 2007

4 Discriminator Values for Rule-In of AMI Sub-Types: Universal Definition

5 Peri-Interventional Myocardial Infarction: Type 4a MI 1.) The Universal Definition 2.) Prevalence and Diagnostic Tools

6 Incidence of Peri-Procedural MI in Elective PCI (in %): Troponin versus CKMB Author Source >3xURL TnI or T >3xURL CKMB >1xURL TnI or T >1URL CKMB Prasad CCVI 2008 TnT 32.0% 6.5% TnT 43.0% 21.0% Brignon JACC 2009 TnI 29.1% 15.8% TnI 52.6% 37.0% Locco JACC 2010 TnI 47.0% 11.0% TnI 58.0% 29.0%

7 Peak CK-MB, Troponin I and LGE for diagnosis of Type 4a MI Lim CS, et al. JACC 2011

8 N=32 CMR reference ctni ultra for most pts (0.06 ug/l) Immulite CKMB (4.8 ug/l) G1: No injury- no elevation G2: URL-Univ. Def. G3: Univ. Definition 5 of 26 G3 with new LGE: PPV 19% 3 of 5 G3 with new LGE: PPV 60% ROC of new LGE: TnI>2.4; CKMB>9.5 (ug/l)

9 Comparison of Site- and Core Laboratory-Reported CK-MB Values (Multiples of ULN) in the SYNERGY Trial Linefsky et al., AJC 2009, 1330

10 Analytical Characteristics of Cardiac Troponins and CKMB Mass Assays as Claimed by Each Manufacturer CKMB data shown do not apply for CKMB determinations by electrophoresis (CKMB bands) or by immuno inhibition assays (CKMB activity) Apple F, et al. Clin Chem 2003

11 LGE After Coronary Microembolization: Poor Sensitivity of MRI for Detection of Small MIs In Vivo LGE IR-FLASH sequence Resolution: 1.3 x 1.7 x 5 mm 3 HR Ex Vivo LGE IR-FLASH sequence Resolution: 0.5 x 0.5 x 2 mm 3 Breuckman F, et al. JACC imaging 2010

12 MRI After Coronary Microembolization: Close Correlation of TnI in Blood with Ex-vivo LGE Breuckman F, et al. JACC imaging 2010

13 Peri-Interventional Myocardial Infarction: Type 4a MI 1.) The Universal Definition 2.) Prevalence and Diagnostic Tools 3.) Pathophysiology of Type 4a MI

14 Angiographic Predictors of Troponin I Elevations after elective PCI Clinical Predictor HR 95% CI p Value Thrombus present Abrupt closure No-reflow Perforation Sidebranch occlusion <0.001 HR = hazard ratio CI = confidence interval B. K. Nallamothu; Am J Cardiol; 2003

15 Coronary Plaque Morphology (Fibrous Cap Thickness) and ctnt post PCI Lee et al., Circ CVI 2011, 378

16 Microembolic count during PCI and ctni after PCI for stable angina r=0.565, P<0.001) Bahrmann P,et al. Circulation 2007

17 Peri-Interventional Myocardial Infarction: Type 4a MI 1.) The Universal Definition 2.) Prevalence and Diagnostic Tools 3.) Pathophysiology of Type 4a MI 4.) Outcome of Type 4a MI in elective PCI

18 Prognostic Role of ctn Elevation post Elective PCI: A Meta-Analysis N=22, trials Outcome: Death PMI-Prevalence: +ctni 34.3% +ctnt 25.9% Feldman DN, et al. Cath Cardvasc Int 2011

19 Individual and summary ORs for the risk of single end points All-cause Death Non-fatal MI Repeat PCI CABG Testa L et al. QJM 2009;102:

20 Incidence and Prognostic Role of Type 4a MI: Universal Definition versus any Tn-Elevation 2359 patients, 4 studies A: 3x99th percentile PCI-related MI: 14.5%. B: <3x99th percentile PCI related elevation of troponin : 28.7% Testa L et al. QJM 2009;102:

21 Troponin I Levels and Outcome in PCI associated MI Cumulative Survival (%) Tn- I > 8x normal Tn- I 5-8x normal Tn- I 3-5x normal Tn- I 1-3x normal TnI > 8x; HR: 2.4 ( ) Tn- I normal n = 2796 Days B. K. Nallamothu; Am J Cardiol; 2003

22 Peri-Interventional Myocardial Infarction: Type 4a MI 1.) The Universal Definition 2.) Prevalence and Diagnostic Tools 3.) Pathophysiology of Type 4a MI 4.) Outcome of Type 4a MI in Elective PCI 5.) The Issue in Pts. with NSTE- ACS

23 30-Day Mortality According to Periprocedural ctnt Levels: The Role of Evolving MI Mortality (%) 2.5 P<0.001 Kaplan-Meier Estimates Pre % /13 events non cardiac Pre <0.01, post > % Pre <0.01, post < % Days from PCI Prasad, Jaffe et al: Circ Cardiovasc Intervent 1:10, 2008

24 Pre-Procedural ctn Elevations in Stable Angina PCI: EVENT Registry Jeremias et al., Circ. 2008,632

25 Joint ESC/ACCF/AHA/WHF Task Force Universal Definition of MI: Type 4a Type 4a MI If cardiac troponin is elevated before the procedure and not stable for at least two samples 6 h apart, there are insufficient data to recommend biomarker criteria for the diagnosis of peri-procedural myocardial infarction. Thygesen K, et al. Eur Heart J 2007

26 CV Mortality According to the Occurrence of Procedure-Related MI in Revascularized NSTE-ACS Patients (FRISCII, ICTUS, RITA3) Damman et al., Circ 2012, 574

27 Time to Event for ctn negative NSTE-ACS Patients on Baseline by Planned Invasive/Non-invasive Treatment Approach in PLATO MI (incl silent) CV death 12 Planned invasive Planned non-invasive 12 Planned invasive Planned non-invasive Cumulative Incidence(%) Cumulative Incidence(%) Time after randomization (months) Time after randomization (months) No at Risk Invasive 901 Non-inv No at Risk Invasive 901 Non-inv Giannitsis E, Wallentin L et al, submitted

28 Joint ESC/ACCF/AHA/WHF Task Force Universal Definition of MI: Type IVa MI Elevations of biomarkers above the 99th percentile URL after PCI, assuming a normal baseline troponin value, are indicative of postprocedural myocardial necrosis. There is currently no solid scientific basis for defining a biomarker threshold for the diagnosis of peri-procedural myocardial infarction. Pending further data, and by arbitrary convention, it is suggested to designate increases more than three times the 99th percentile URL as PCI-related myocardial infarction (type 4a). Thygesen K, et al. Eur Heart J 2007

29 Joint ESC/ACCF/AHA/WHF Task Force Universal MI Definition: Type 4a There appears to be a positive relationship between mass of PCI associated myocardial injury and outcome in elective PCI of stable CAD patients. However the optimal discriminator value for risk assessment is as yet undefined. The use of CKMB instead of a more cardio-specific and sensitive troponin- to restrict the diagnosis to more extensive injury- ignores the imprecission of CKMB assays and their variation in upper reference limits. LGE on MRI lacks sensitivity for diagnosis of PCI related injury. It`s role for risk assessment in Type 4a needs to be studied in larger cohorts.

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31 Back Up Slides

32 High Sensitivity Assays: Is there a Type 4a AMI in Diagnostic Coronary Angiography?

33 Relationship of Troponins versus CKMB for Detection of PMI Synergy / Early ACS ctnt 60x ULN CKMB 3x ULN EVENT ctn 35x ULN CKMB 5x ULN MICASA ctn 40x ULN CKMB 3x ULN Vranckx CKMB < 3 ULN ctn > 3 ULN = 19% ctn vs CK Rate PMI > 3 ctn vs CKMB Rate PMI > 2

34 Correlations Between SPECT-MPI Infarct Size and Troponin Arruda-Olson AM, et al. JACC imaging 2011

35 Performance of Troponin Testing in Infarct Subtypes Giannitsis E, et al. JACC 2008

36 What about highly sensitive ctn assays?

37 Distribution of new or recurrent MIs (n=1218) by the universal definition of MI clinical classification Morrow, D. A. et al. Circulation 2009;119:

38 Timing of Peak Elevations After elective PCI 25 83% % 5 0% 4% 0 2h 4h 8h 12-20h 24 of 57 pts (46%) ctn positive Monitoring for elevations in ctnt and CK-MB at 6 to 8 h following elective catheter-based coronary artery interventions will not detect peak elevations in the majority of patients. Miller WL, et al.chest 2004

39 LGE After Coronary Microembolization: Poor Sensitivity of MRI for Small MIs In Vivo LGE High-Resolution Ex Vivo LGE Breuckman F, et al. JACC imaging 2010

40 Kaplan-Meier survival estimates for those with and without TnT post PCI 1,949 patients from the Mayo Clinic registry All had normal CK-MB after the procedure 383 (19.6%) patients with elevated ctnt Prasad, A. et al. J Am Coll Cardiol 2006;48:

41 Mortality (%) Long-Term Mortality According to Periprocedural ctnt Levels P<0.001 Pre 0.01 Pre <0.01, post >0.01 Pre <0.01, post < Months from PCI Prasad, Jaffe et al: Circ Cardiovasc Intervent 1:10, 2008