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Kwong

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Kwong

  1. 1. Detecting Acute Coronary Syndrome in the Emergency Department with Cardiac Magnetic Resonance Imaging Raymond Y. Kwong MD Co-Director, Cardiac Magnetic Resonance Imaging Brigham and Women’s Hospital Cardiology Grand Round Beth Israel Deaconess Hospital April 11th , 2003
  2. 2. Acknowledgments NHLBI • Andrew E. Arai, MD • Robert S. Balaban, PhD • Anthony Aletras, PhD • Adam Schussheim, MD • Suresh Rekhraj, MD • W. Patricia Ingkanisorn, MD • Kenneth Rhoads, MD Clinical Center • Janice Davis, RN • Grace Graninger, RN Suburban Hospital • Cardiology Eugene Passamani, MD • Emergency Room Bob Rothstein, MD • Radiology Wayne Olan, MD Susan O’Flahavan, RT Paul LeBlanc, RT Gian Serafini, RT Chris Mancini, RT Sarah Pirie, RT
  3. 3. Myocardial Infarction and Chest Pain in the Emergency Room • 1,100,000 MI per year in the US About 1/3 will die from their MI * • 6,200,000 people in the United States suffer from angina • 5,000,000 patients are evaluated in ER for chest pain each year American Heart Association. 1999 Heart and Stroke Statistical Update. * Atherosclerosis Risk in Communities (ARIC) study, NHLBI
  4. 4. The Spectrum of Chest Pain in the ER Chest Pain STEMI NSTEMI Unstable Angina ACS Troponin Non-cardiac Chest Pain Stable Angina
  5. 5. Mortality of ER patients with chest pain Pope et al. NEJM 2000; 342: 1163
  6. 6. Chest Pain in Emergency Department LCE/NHLBI/NIH ST Elevation Acute MI PTCA or Thrombolytics Intermediate Likelihood CAD Cardiac Rx Non-STE MI Unstable Angina Low Likelihood CAD Cardiac Enzymes
  7. 7. Regional Wall Motion: SSFP Dobutamine Stress MRI Sensitivity 83-86% Specificity 83-86% Nagel Circ 1999; 99: 763 Hundley Circ 1999; 100: 1697
  8. 8. Interobserver Variability for Qualitative Regional Wall Thickening by MRI Versus Consensu s Observer 1 Observer 2 Observer 3 Observer 4 Correlati on 0.95 0.96 0.93 0.95 Avg Dif -0.02 -0.03 0.01 -0.02 SD of Dif 1.3 1.6 2.0 1.3 Sierra-Galan et al. JCMR in press
  9. 9. First Pass Perfusion RV LV Myo LCE/NHLBI/NIH
  10. 10. Comparison of Endocardial Microsphere Blood Flow and Endocardial MRI Contrast Enhancement Ratio 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 y = 0.04 + 0.85x r = 0.92 Endocardial Microsphere Flow (ml/min/g) MRIEndocardialCER NHLBI/NIH
  11. 11. Dipyridamole Stress MRI vs PET and QCA Schwitter et al. Circ 2001; 103:2230
  12. 12. Dipyridamole Stress MRI vs PET and QCA Schwitter et al. Circ 2001; 103:2230 MRI Vs PET Sensitivity 91% Specificity 94% MRI Vs QCA Sensitivity 87% Specificity 85%
  13. 13. Dipyridamole Stress First Pass Perfusion Myocardial Perfusion Reserve Index Al-Saadi et al Circ 2000; 101:1379 MPR + 54 7 MPR - 6 35 Sensitivity 90% Specificity 83% CAD+ CAD -
  14. 14. 0 50 100 150 200 0 5 10 15 20 Time (s) SignalIntensity Width = τ 0 Fermi Function Decay rate = κ Flow 0 500 1000 1500 2000 2500 3000 0 5 10 15 20 Time (s) SignalIntensity Fermi Function Deconvolution Estimates Absolute Myocardial Perfusion (ml/min/g) Input Function Myocardial Enhancement Mathematical Model
  15. 15. Endocardial and Epicardial Analysis R = 0.92, P< 0.0001 R = 0.95, P < 0.0001
  16. 16. Infarct Size: TTC vs MRI Kim R. et al. Circulation. 1999;100:1992-2002
  17. 17. Correlation between MRI Infarct Size and TTC Staining Kim R. et al. Circulation. 1999;100:1992-2002
  18. 18. Kim RJ et al. NEJM 2000;343:1445 Irreversible LV Dysfunction: Pre-intervention After revascularization Diastole Systole Diastole Systole Transmural Hyper
  19. 19. 0 20 40 60 80 100 0 1-25 26-50 51-75 76-100 0 20 40 60 80 100 0 1-25 26-50 51-75 76-100 Transmural Extent of Hyperenhancement Predicts Recovery of Function Transmural Extent of Hyperenhancement (%) ContractileRecovery(%) ContractileRecovery(%) Kim RJ et al. NEJM 2000;343:1445 All segments Akinetic or Dyskinetic
  20. 20. PET vs MRI Viability Klein et al. Circulation 2002; 105: 162
  21. 21. Microinfarction after PCI associated with Minor Side Branch Occlusion Ricciardi. Circulation 2001;103:2780-3 Patient 7: stent in the proximal LAD and minor side-branch occlusion Patient 2: stent in the mid-PDA and minor side-branch occlusion MI size = 0.7 to 12 g
  22. 22. Comparison of MRI and SPECT for Detecting Myocardial Infarction Wagner et al. Lancet 2003; 361: 374
  23. 23. Method: Acute Chest Pain Protocol Localize Perfusion Function Viability Time (min)0 10 20 30
  24. 24. Pilot phase • To determine safety, feasibility, and logistic issues: • 37 patients presenting with chest pain to the ER were studied. – Patients were either from the ER or within 72 hours of admission to the hospital. » Well tolerated (1 failure to acquire any image due to clasutophobia) » 13 cases of AMI with a wide range of troponins all have abnormal MRI » Can perform MRI while receiving concurrent IV meds.
  25. 25. Case 1: 60 yo male Day 2 post acute MI Troponin 2X ULN
  26. 26. Case 2: 80 yo female No prior CAD Chest pain with non-diagnostic EKG admitted 12 hours ago, small NQMI by troponin
  27. 27. Case 2: 70 yo male No prior CAD Chest pain with non-diagnostic EKG admitted 12 hours ago, small NQMI by troponin
  28. 28. Hypothesis • We hypothesized that MRI could effectively triage patients presenting with possible acute coronary syndromes in the Emergency Room
  29. 29. Entry Criteria • 30 minutes of chest pain compatible with myocardial ischemia • ECG not diagnostic of ST-elevation MI Exclusions • Pacemaker • Defibrillator • Other implanted active devices • Brain aneurysm clips
  30. 30. Method Prospective observational trial. • Enrollment from 01/10/2000 to 09/27/2001 • Inclusion criteria: • Chest pain > 30 minutes without obvious non-cardiac cause • Exclusion criteria: any of the following • ECG diagnostic of ST elevation acute myocardial infarction • Ongoing active chest pain • Hemodynamic instability • Contraindications to MRI scanning • > 12 hours since onset of last chest pain .
  31. 31. Symptoms Suggestive of ACS Noncardiac diagnosis Stable Angina Possible ACS Definite ACS ACC/AHA Practice Guidelines Unstable Angina And NSTEMI Circ 2000;102:1193 ST Elevation MI Confirmed ACS ECG Not Diagnostic Troponin (-) Serial Studies ? Image Stress Test - + + - + - + Unstable Angina ST or T and/or Troponin (+) + Non-ST Elevation MI -
  32. 32. Method: Prospectively Defined Clinical Endpoints Acute coronary syndrome (ACS): Possible or definite ACS according to ACC/AHA guidelines
  33. 33. Method: Prospectively Defined Clinical Endpoints Acute coronary syndrome (ACS): Possible or definite ACS according to ACC/AHA guidelines as indicated by chest pain > 30 minutes (an entry criteria) AND either angiographically significant CAD AND/OR significantly abnormal stress testing performed during index hospitalization or the subsequent 6- 8 week follow-up period. Non-ST elevation acute myocardial infarction (NSTEMI): Abnormal troponin-I with a temporal pattern consistent with acute MI and clinical evidence of coronary artery disease (Coronary angiography, echo, or noninvasive imaging).
  34. 34. Method: Definitions Angiographically significant CAD = 1) > 50% left main lesion or 2) > 70% epicardial coronary artery stenosis
  35. 35. Method: Prospectively Defined Abnormal MRI Abnormal defined by either: • Regional wall motion abnormality (RWMA), or • Myocardial hyperenhancement (Hyper). Reading included perfusion images: • Although independent diagnoses were not made using perfusion alone, the perfusion images helped identify abnormal regions.
  36. 36. TIMI risk score Antman et al. JAMA 2000; v284;7:835
  37. 37. Results: Study population • 193 consecutive patients • 11 refused to participate • 21 excluded: –6 hemodynamically unstable –2 metallic implants –3 large body size –10 claustrophobia • Remaining 161 formed the study cohort. • All patients underwent conventional cardiac workup as determined by the admitting cardiologists or ER physician
  38. 38. 161 enrolled •92 Male : 69 Female •Age: 59 + 15 years old •Average # of risk factors: 3.4 •History of prior MI: 25/161 •Median time since ER arrival: 2.7 hours (off hours cases excluded) 6.0 hours (off hours cases included) •Average MRI scan duration: 38 + 12 minutes Results: Study population
  39. 39. Patient Follow-up at 6 –8 weeks 161 patients • 158 (98%) were successfully contacted at 6-8 week follow-up • 3 were lost to follow-up: all troponin negative, 2 clinical low risk with normal MRI and 1 high risk with abnormal MRI
  40. 40. Results: Demographic summary ACS (n = 25) No ACS (n = 136) p value Age (yr) 68 + 13 57 + 14 p = 0.0006 Men (%) 60 57 NS CAD risk factors Advanced Age (M>45, W>55) (%) 92 68 p = 0.03 Hypertension (%) 56 43 NS Diabetes (%) 28 10 p < 0.001 Hypercholesterolemia (%) 64 47 NS CAD in family (%) 32 42 NS Hx. of smoking (%) 48 39 NS Total number of CAD risk factors 4.2 3.2 p = 0.003 Characteristics of Chest Pain Location Substernal (%) 32 31 NS Precordial (%) 24 18 NS Quality Crushing, heaviness, pressure or tightness (%) 56 54 NS Radiation to neck/arm (%) 32 31 NS Dyspnea, diaphoresis, or nausea (%) 32 40 NS Previous angina (%) 40 12 p = 0.001 Average Chest Pain Score 8.4 7.5 NS ( p= 0.06) TIMI risk score P < 0.00011.6 + 0.82.5 + 1.2
  41. 41. Table 1. Demographic Summary ACS n = 25 68 + 13 28% 40% 8.4 2.5 + 1.2 No ACS n = 136 57 + 14 10% 12% 7.5 1.6 + 0.8 p value 0.0006 0.001 0.001 0.06 0.0001 Age Diabetes HTN CP Score TIMI Risk Score Kwong et al. Circulation 2003; 107:531-7
  42. 42. 11620No ACS 421 + MRI ACS - MRI
  43. 43. Results: Qualitative MRI assessment compared with clinical evaluation ( N = 161) MRI History of MI ECG Strict ECG Initial Troponin- I Peak Troponin- I TIMI Risk Score ACS Sensitivity (%) 84 28 80 19 16 40 76 Specificity (%) 85 87 61 95 97 97 52 NonSTE MI Sensitivity (%) 100 30 70 20 44 NA 80 Specificity (%) 79 85 56 94 97 97 50 IHD Sensitivity (%) 91 51 79 14 10 24 81 Specificity (%) 98 97 67 96 97 97 58
  44. 44. Sensitivity and Specificity for ACS 0 10 20 30 40 50 60 70 80 90 100 MRI ECG ECG strict Trop Trop peak TIMI SensitivityorSpecificity(%) Sensitivity Specificity NS 0.001 0.001 0.004 NS 0.001 0.001 0.011 0.001 0.001 Sensitivity Specificity Kwong et al. Circulation 2003; 107:531-7
  45. 45. Multivariate Logistic Regression Analysis: Predict Acute Coronary Syndrome 0 20 40 60 80 100 0 20 40 60 80 100 False Positive Portion (1 - specificty, %) TruePositivePortion (Sensitivity,%) TIMI Risk Score NIH with MRI NIH without MRI Kwong et al. Circulation 2003; 107:531-7
  46. 46. Detecting CAD by presence of Regional Wall Motion Abnormality (RWMA) 1231No IHD 864IHD No RWMARWMADetect IHD Sensitivity: 89% Specificity: 99% Regional wall motion images were interpretable in 196/197 patients (99%)
  47. 47. Detecting CAD by Delayed Hyperenhancement (HYPER) 1121No IHD 2448IHD HYPERDetect IHD Sensitivity: 67% Specificity: 99% No HYPER Delayed hyperenhancement images were acquired and interpretable in 185/197 patients (94%)
  48. 48. Methods Anterior Septum Lateral wall RWMA Inferior Septum
  49. 49. D S End-systolic thickness (S) in mm End-diastolic thickness (D) in mm Absolute wall thickening in mm = S - D Systolic diastolic ratio = S/D Percent change in wall thickening (%) = (S-D)/D x 100% Methods
  50. 50. 0 20 40 60 80 100 0 20 40 60 80 100 False Positive Portion (1 – specificity, %) TruePositivePortion (Sensitivity,%) 0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100 False Positive Portion (1 – specificity, %) 0 20 40 60 80 100 False Positive Portion (1 – specificity, %) ACS Non-STE MI IHD Receiver Operator Characteristic Analysis: Quantitative Wall Thickening 3220 Kwong et al. Circulation 2003; 107:531-7
  51. 51. 84 year old female with Acute Non-ST Elevation MI -20 0 20 40 60 80 100 120 140 160 0 10 20 30 Time (image number) SignalIntensity -50 0 50 100 150 200 250 300 350 400 450 500 0 10 20 30 Time (image number) SIIntegral 33%
  52. 52. 68 year old female, with 2 hours CP, no risk factors, nonspecific ECG, and normal troponin
  53. 53. 68 year old female, with 2 hours CP, no risk factors, nonspecific ECG, and normal troponin
  54. 54. A 53 year old female with 3 days of intermittent rest chest pain
  55. 55. A 53 year old female with 3 days of intermittent rest chest pain
  56. 56. A 53 year old female with 3 days of intermittent rest chest pain
  57. 57. Adenosine Stress Rest SSFP Adenosine Perfusion Gd Hyperenhancement 67 year old female with no prior CAD + DM, FMH, Tob, HTN Troponin (-) Cath: RCA 99%, Cx 99%, LAD 75%
  58. 58. Cardiac MRI Unit The General Infirmary at Leeds Diastolic Systolic Perfusion LAD/LCX RCA Delayed image MRI conclusion: significant mid RCA lesion X-ray angiogram
  59. 59. Comprehensive Approach to Chest Pain: MRI: Does It Have Any Role? • ST Elevation MI • Post-MI risk stratification • Detection of residual ischemia • Viability • Non-ST elevation MI • Same as ST elevation MI • Also potential for more rapid diagnosis • Unstable angina • Early rest scan to detect evidence of recent ischemia • Alternatively, scan after excluding MI with a stress test
  60. 60. Conclusions • Use of cardiac MRI in the ER in assessment of patients presenting with chest pain and a non-diagnostic ECG is feasibility and safe. • Cardiac MRI has high sensitivity and specificity for detecting ACS, NSTEMI, and IHD in patients with chest pain, and could provide useful diagnostic information beyond clinical assessment. • MRI parameters could be interpreted both qualitatively and quantitatively with high accuracy in prediction of clinical endpoints • Further work is needed to differentiate acute from chronic myocardial infarction and to improve scan efficiency.
  61. 61. Conclusions • Add a slide: The additional benefit of adenosine stress testing Cost effectiveness of early patient triage translating into savings in health care cost dollars 12 months prognostic data
  62. 62. Clinical Cases
  63. 63. 50 yo male lawyer, atypical chest pain First troponin negative
  64. 64. 60 yo female presenting with an episode of prolonged chest pain 24 hours ago, then another episode for several minutes.
  65. 65. 60 yo female presenting with “good story” of unstable angina. EKG: NSST changes First troponin 3X ULN
  66. 66. Cath during index hospitalization: NS stenosis Uneventful at 6 weeks on no medications

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