Prognostic Value of Intramyocardial Hemorrhage Detected by Cardiac Magnetic Resonance Imaging in Acute Reperfused ST-Elevation Myocardial Infarction

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1 Prognostic Value of Intramyocardial Hemorrhage Detected by Cardiac Magnetic Resonance Imaging in Acute Reperfused ST-Elevation Myocardial Infarction Holger Thiele, MD; Konrad Kubusch, BSc; Steffen Desch, MD; Oliver Strohm*, MD, Georg Fuernau, MD;, Suzanne de Waha, MD; Matthias Gutberlet, MD; Gerhard Schuler, Matthias G. Friedrich*, MD and Ingo Eitel, MD University of Leipzig Heart Center, Germany *University of Calgary, Canada

2 Disclosures Prognostic Value of Intramyocardial Hemorrhage Detected by Cardiac Magnetic Resonance Imaging in Acute Reperfused ST-Elevation Myocardial Infarction Nothing to disclose for any of the authors

3 Infarct size (%) Background Effects of Reperfusion No Reperfusion Infarct size % Reperfusion Infarct size reduction by 40% Partly by reperfusion injury + hemorrhage Reperfusion plus cardio protection Infarct size 5% Adapted according to Yellon et al. NEJM 2007; 357:

4 Event-free survival (%) Event-free survival (%) Background Late MO + MACE Presence of late MO Extent of late MO p< p< no MO 20 MO Time to event (months) Tertile 1 Tertile 2 Tertile Time to event (months) De Waha et al. Eur Heart J 2010; doi: /eurheartj/ehq247

5 Background Hemorrhage in MRI Microvascular obstruction is known to be a independent powerful of adverse outcome. Recently, intramyocardial hemorrhage has been introduced as a new potential CMR parameter in STEMI patients Hemorrhage can be visualized by T2-weighted and/or T2*-weighted CMR -breakdown products of hemoglobin are paramagnetic and -influence regional magnetic tissue properties The hypointense core in T2/Hemorrhage is related to adverse remodeling. Additional prognostic value for clinical events of hemorrhage in T2-weighted images? Ganame et al. Eur Heart J 2009;30, O Regan et al. Radiology 2009;250:

6 Background Hypointense Core in T2 (Hemorrhage) Lotan et al Circulation 1992;86; Basso et al Am J Cardiol 2008;100; Ganame et al Eur Heart J 2009;30,

7 Aims To evaluate the prognostic value and determinants of a hypointense core in T2-weighted imaging in STEMI patients reperfused by primary PCI

8 Methods Hemorrhage Study 62 patients 346 STEMI patients 284 patients

9 Methods Trial Profile Eligible STEMI patients < 12 h (n=407) No inclusion (n=4): No informed consent (n=4) No CMR (n=57): Claustrophobia (n=19) Death (n=14) Technical reasons (n=7) Refusal (n=6) Patient discomfort (n=6) Obesity (n=5) CMR (n=346) Hypointense core in T2 CMR present (n=122) Hypointense core in T2 CMR absent (n=224) Lost to 6 month follow-up (n=2) Endpoint analysis (n=120) Lost to 6 month follow-up (n=9) Endpoint analysis (n=213)

10 Methods Endpoint Analysis Primary composite endpoint (MACE): Death Myocardial re-infarction New-onset CHF (requiring hospital admission) Follow-up was conducted after 6 months

11 Methods MR Image Acquisition Contrast-injection 2 mmol/kg/bw Bolus Gadobutrol i.v CH+2 CH T2 SA DE early SA Short axes 30 DE late 4CH+2CH+SA Time (min) Survey SSFP sequence (TR/TE/flip = 3.2/1.2/60 ) 3D IR GRE sequence (TR/TE/flip 2.8/1.1/15 ) Thiele et al. JACC 2010; 2010;55:

12 Methods MR Image Analysis Blinded observers: Manual drawing of Edema, endocardial, epicardial, papillary, Infarcted MO Hemorrhage contours Area at risk = Volume Edema/Volume LV mass %Infarct Size = Volume Infarct/Volume LV mass %MO = MO-Volume/Volume LV mass %Hemorrhage = T2 hypointense core/volume LV mass Myocardial salvage = Edema-Infarct Size Myocardial salvage index = Edema-Infarct Size/Edema Thiele et al. JACC 2010; 2010;55: Eitel et al. JACC 2010; 55:

13 Results Patient Characteristics Variable All patients (n=346) Hypo Core present (n=122) No Hypo Core (n=224) p-value Age (years) 64 (53-73) 62 (53-72) 65 (54-73) 0.29 Male sex; No. (%) 256 (74) 94 (77) 162 (72) 0.34 Cardiovascular risk factors; No. (%) Current Smoking Hypertension Hypercholesterolemia Diabetes mellitus 140 (41) 222 (64) 121 (35) 78 (23) 56 (46) 76 (62) 40 (33) 29 (24) 84 (38) 146 (65) 81 (36) 49 (22) Anterior myocardial infarction; No. (%) 158 (46) 65 (53) 93 (42) 0.04 Reperfusion times (minutes) Symptom-onset-to-reperfusion Door-to-balloon time 194 ( ) 28 (20-36) 190 ( ) 26 (20-35) 180 ( ) 28 (22-36) TIMI-flow grade before PPCI 1; No. (%) 244 (71) 106 (87) 138 (62) <0.001 TIMI-flow grade after PPCI < 3; No. (%) 33 (10) 18 (15) 15 (7) 0.03 Glycoprotein IIb/IIIa-inhibitor; No. (%) 322 (93) 117 (96) 205 (92) Medication at discharge; No. (%) Beta-blockers ACE-inhibitors/AT-1 antagonist Aspirin Clopidogrel Statins Aldosterone antagonist 341 (99) 342 (99) 346 (100) 346 (100) 341 (99) 11 (3) 120 (98) 121 (99) 122 (100) 122 (100) 120 (98) 6 (5) 221 (99) 221 (99) 224 (100) 224 (100) 221 (99) 4 (2)

14 Results MRI Results Variable Hypo Core present (n=122) No Hypo Core (n=224) p- value Area at risk/edema (%LV) 38.9 ( ) 32.2 ( ) <0.001 Infarct size (%LV) 27.1 ( ) 13.0 ( ) <0.001 Late MO present; No (%) 122 (100) 108 (48) <0.001 Late MO (%LV) 2.1 ( ) 0.1 ( ) <0.001 Myocardial salvage (%LV) 11.5 ( ) 15.8 ( ) <0.001 Myocardial salvage index 28.5 ( ) 58.1 ( ) <0.001 LV ejection fraction (%) 46.8 ( ) 57.0 ( ) <0.001 LV enddiastolic volume (ml) ( ) ( ) <0.001 LV endsystolic volume (ml) 77.4 ( ) 55.0 ( ) <0.001

15 Results Logistic Regression for Hypo Core Presence Predictors Univariable Stepwise Multivariable OR 95% CI p HR 95% CI p Age (years) Male sex Current smoking Hypertension Hypercholesterolemia Diabetes mellitus Anterior myocardial infarction Door-to-balloon time (min) Symptoms-reperfusion time (min) TIMI-flow grade before PCI < TIMI-flow after PCI < Area at risk (%LV) < Infarct size (%LV) < Myocardial Salvage Index < Extent late MO (%LV) < <0.001 LV ejection fraction (%) <

16 Results Endpoint Analysis Overall 35 MACE events recorded: - death: 12 patients - myocardial reinfarction: 10 patients - new congestive CHF: 13 patients MACE-rate: 10.5%

17 Cumulative event rate (%) Cumulative event rate (%) Results Hypointense Core vs. MO + Outcome 20 Hypointense core MO + 10 Hypointense core MO - 0 log-rank test p= Time (days after infarction) log-rank test p= Time (days after infarction)

18 Results Patient Examples MO Hypo Core - N=116 MO + Hypo Core + N=122 T2 DE MO + Hypo Core N=108

19 Cumulative event rate (%) Results Hypointense Core + MO and Outcome 20 MO + and hypointense core + 15 MO only MO - and hypointense core - 0 log-rank test p= Time (days after infarction)

20 Results Predictors of MACE Uni - + stepwise multivariable Cox-regression analysis Univariable Stepwise multivariable Variable Hazard Ratio (95% CI) p Hazard Ratio (95% CI) p Age 1.04 ( ) ( ) TIMI-flow after PCI < ( ) Presence late MO 4.23 ( ) ( ) 0.03 Presence hypointense core 2.59 ( ) Infarct size > median 2.39 ( ) LV-EF < median 3.01 ( ) ( ) 0.04

21 Results Predictors of MACE MO Hypo Core Uni - + stepwise multivariable Cox-regression analysis Univariable Stepwise multivariable Variable Hazard Ratio (95% CI) p Hazard Ratio (95% CI) p Age 1.04 ( ) ( ) TIMI-flow after PCI < ( ) Presence late MO only 1.19 ( ) Presence hypointense core + late MO 2.59 ( ) ( ) 0.04 Infarct size > median 2.39 ( ) LV-EF < median 3.01 ( ) ( ) 0.04

22 Prognostic relevance Prognostic Implications Prognostic relevance validated Prognostic relevance validated Prognostic relevance validated Prognostic relevance partly validated Prognostic relevance partly validated Hemorrhage Myocardial salvage LV volumes + ejection fraction Infarct size Microvascular obstruction

23 Limitations: T2* vs T2 A B A B C D C D E ROI 1: T2* = 20±1 ms EF E ROI 1: T2* = 19.9±0.8 ms F ROI 1: T2* = 32±2 ms ROI 1: T2* = 7.8±0.4 ms Cannan, Eitel et al. JACC Img. 2010;3;

24 Summary + Conclusions A hypointense core within the AAR of reperfused infarcted myocardium in T2-weighted CMR is a frequent finding (1/3 of patients) in reperfused STEMI patients. It is closely related to infarct size and MO. A hypointense core in T2-weighted images adds prognostic information on top of MO with regard to MACE. However, larger trials are warranted to further investigate the prognostic significance of hypointense infarct cores.

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