1. J Am Coll Cardiol 2008;51:2230–8 Relation Between the Assessment of Microvascular Injury by Cardiovascular Magnetic Resonance and Coronary Doppler Flow Velocity Measurements in Patients With Acute Anterior Wall Myocardial Infarction Alexander Hirsch, Robin Nijveldt, Joost D. E. Haeck, Aernout M. Beek, Karel T. Koch, José P. S. Henriques, Rene J. van der Schaaf, Marije M. Vis, Jan Baan, JR, Robbert J. de Winter, Jan G. P. Tijssen, Albert C. van Rossum, Jan J. Piek, Amsterdam and Utrecht, the Netherlands

2. Introduction “no-reflow” phenomenon Structural disruption or obstruction of the microvasculature Microvascular obstruction common phenomenon Associated with increased infarct size reduced myocardial function left ventricular (LV) remodeling worse clinical outcome prognostic significance in patients after acute MI

3. Earlier studies to assess and quantify microvascular injury in acute MI Heart 2006;92:1113– 8. J Am Coll Cardiol 1998;32:1756–64. Characteristics of coronary blood flow velocity patterns Early systolic retrograde flow (SRF), Rapid deceleration of diastolic flow Reduced coronary flow velocity reserve (CFVR)

4. Aim of the present study determine whether the presence and severity of microvascular injury determined by gadolinium-enhanced CMR was related to intracoronary Doppler flow measurements for assessment of myocardial reperfusion

5. Methods Patients and study protocol 27 consecutive patients presenting with a first acute anterior ST- segment elevation MI treated by successful primary PCI Inclusion criteria PCI within 12 h after onset of symptoms > 10-fold increase in serum CK-MB levels wall motion abnormalities in ≥ 3 segments observed on resting echocardiogram Exclusion criteria previous MI 3-vessel disease cardiogenic shock (relative) contraindications for CMR significant comorbidities

6. Methods CMR protocol, data analysis and definitions. ECG gating, phased array cardiac receiver coil 1.5-T clinical scanner (Sonata, Siemens, Erlangen, Germany) late gadolinium-enhanced images - determine infarct size and microvascular obstruction size and extent. analyzed on a separate workstation using dedicated software LV volumes, ejection fraction, Segmental LV function, Systolic wall thickening Infarct size and regions of microvascular obstruction standardized and pre-defined definition of hyperenhancement extent of transmural necrosis sum of segments with > 75% transmural hyperenhancement as a percentage of the total number of segments scored Microvascular obstruction hypoenhanced regions within the hyperenhanced infarcted area

7. Methods Cardiac catheterization bolus of 0.1-mg nitroglycerin before flow measurements 0.014-inch Doppler-tipped guidewire (FloWire, Volcano Corporation, Rancho Cordova, California) distal to the previously implanted stent Velocity recordings at rest and after induction of maximal hyperemia with an intracoronary bolus of 20 to 40 ug adenosine. Reference : LCX, RCA Analysis of Doppler flow measurements. baseline average and maximum peak flow velocity diastolic and systolic average peak flow velocity diastolic–systolic flow velocity ratio diastolic deceleration time diastolic deceleration rate early systolic retrograde flow retrograde peak velocity ≥10 cm/s and duration of > 60 ms coronary flow velocity reserve the ratio of hyperemic to baseline average peak flow velocity

8. Figure 1 Examples of Coronary Flow Velocity Recordings and Corresponding LGE Images of Patients Without and With the Presence of Microvascular Injury

9. Table 1 Clinical, Angiographic, and CMR Data of Patients With or Without Early Systolic Retrograde Flow on Coronary Flow Velocity Pattern < <

10. Table 2 Clinical, Angiographic, and CMR Data According to the Presence and Extent of MO Measured by CMR <<

11. Table 3 Coronary Flow Velocity Data and Hemodynamics According to the Presence and Extent of MO Measured by CMR << >> >> << > >

12. Figure 2 Relationship Between DDR and the Extent of Microvascular Obstruction as Measured by CMR

13. Extent of microvascular obstruction Diastolic–systolic flow velocity ratio (r = 0.44; p = 0.02) Diastolic deceleration time (r = 0.61; p = 0.001) Diastolic deceleration ratio (r = 0.75; p <0.0001) Coronary flow velocity reserve of the infarct-related artery (r = 0.44; p = 0.02) Size of microvascular obstruction Diastolic–systolic flow velocity ratio (r = 0.46; p = 0.01) Diastolic deceleration time (r = - 0.53; p = 0.004) Diastolic deceleration ratio (r = 0.56; p = 0.002) Coronary flow velocity reserve of the infarct-related artery (r = -0.36; p = 0.07) Early systolic retrograde flow Diastolic deceleration ratio Coronary flow velocity reserve Early systolic retrograde flow Coronary flow velocity reserve

14. Table 4 Uni- and Multivariate Logistic Regression Analysis for the Relation Between CMR Parameters and the Presence of Early Systolic Retrograde Flow Table 5 Uni- and Multivariate Linear Regression Analysis for the Relation Between CMR Parameters and the Diastolic Deceleration Rate

15. Discussion Microvascular abnormalities present in myocardium exposed to prolonged ischemia tissue edema, platelet plugging, neutrophil adhesion, myonecrosis, and intracapillary red blood cell stasis enhanced by reperfusion injury within the early stages after reperfusion therapy Timing of perform CMR and recatheterization > 48 h but within 8 days after primary PCI Experimental studies infarct size and the area of MO increase in the first 48 h after reperfusion and stabilize between 2 and 9 days better predictive accuracy for LV recovery and remodeling

16. Early systolic retrograde flow inability to squeeze blood forward into the venous circulation during systole, and consequently blood will be pushed back into the epicardial coronary artery rapid decline of diastolic velocity (short diastolic DT) reduced intramyocardial blood pool, which fills rapidly during diastole Coronary flow velocity reserve functional status of the distal microvascular bed Myocardial resistance, metabolic demands, neurohormonal activation, filling pressures, and vascular resistance of small and large coronary arteries

17. Regions of microvascular obstruction in LGE CMR Hypoenhanced regions within the hyperenhanced infarcted area Delayed contrast penetration reduced functional capillary density capillary compression and obstruction hemorrhage Slowly hyperenhanced over time -> timing ? influences the incidence and extent of MO 12 to 15 min after contrast injection Optimal timing ?

18. Clinical implications Evaluation of MO identifying high-risk patients with an acute MI after successful PCI Facilitate decision making regarding the necessity of additional interventions, such as cell therapy Study limitations Selected population of patients with anterior MI The number of patients Microvascular obstruction was assessed 12 to 15 min after contrast administration rather than during the first 3 min as in previous studies

19. Conclusions The extent and size of MO as assessed by LGE CMR correlated well with coronary blood flow velocity characteristics of microvascular injury, such as the presence of SRF, rapid deceleration of diastolic flow, and a reduced CFVR This relation was independent of the size and transmural extent of the infarcted myocardium