TIMI myocardial perfusion grade

Associate Editor-In-Chief:

Assistant Editor-In-Chief: Kristin Feeney [mailto:kfeeney@perfuse.org]

Overview
The TIMI Myocardial Perfusion Grade (TMPG) was invented by C. Michael Gibson, M.S., M.D. et. al. using a gray scale "myocardial blush" (an angiographic opacification of the myocardial microvasculature or vessels that are not visually apparent) classification. TMPG evaluates myocardial blush which has a distinctive “ground-glass” appearance.

Clinical Importance and Evaluation
Studies of myocardial constrast echocardiography (MCE) and angiography have demonstrated that restoration of epicardial flow does not necessarily lead to restoration of tissue level or microvascular perfusion. Perfusion of the myocardium can also be assessed using the angiogram. In the TMPG system, TMPG 0 represents minimal or no myocardial blush; in TMPG 1, dye stains the myocardium, and this stain persists on the next injection; in TMPG 2, dye enters the myocardium but washes out slowly so that dye is strongly persistent at the end of the injection; and in TMPG 3, there is normal entrance and exit of dye in the myocardium. Another method of assessing myocardial perfusion on the angiogram is the myocardial blush grade (MBG) developed by van’t Hof et al. A grade of 0 (no blush) and a grade of 3 (normal blush) are the same in the TMPG and MBG systems. An MBG grade 1 or 2 represents diminished intensity in the myocardium and corresponds to a value of 0.5 in the expanded TMPG grading system. A TMPG of 1 or a stain in the TIMI system is subsumed within the value of a 0 in the MBG system. Thus, normal perfusion in the myocardium carries a score of 3 in both the TMPG and MBG systems, and a closed muscle carries a score of 0 in both systems. Lepper et al. have demonstrated that angiographic and echocardiographic myocardial perfusion are closely related, and among patients undergoing primary PCI for acute MI, impaired MBG was the best multivariate predictor of nonreperfusion on myocardial contrast echocardiography.

Independent of flow in the epicardial artery and other covariates such as age, blood pressure, and pulse, the TMPG has been shown to be multivariate predictors of mortality in acute STEMI at 2 years. The TMPG permits risk stratification even within epicardial TIMI grade 3 flow. Despite achieving epicardial patency with normal TIMI grade 3 flow, those patients whose microvasculature fails to open (TMPG 0/1) have a 7-fold increase in mortality compared with those patients with both TIMI grade 3 flow in the epicardial artery. Achievement of both TIMI grade 3 flow in both the artery and the myocardium is associated with a mortality under 1%10. Likewise, in the setting of primary PCI, both van’t Hof et al. and Haager et al. have demonstrated an association between impaired myocardial perfusion and early and late mortality. These improvements in early and late mortality may be mediated by improvements in myocardial salvage. As Dibra et al. have demonstrated, restoration of TMPG 2/3 is associated with a higher salvage index (0.49±0.42 versus 0.34±0.49, P=0.01) and a smaller final infarct size (15.4±15.5% versus 22.1±16.2% of the left ventricle, P=0.001). Indeed, second only to stent placement, restoration of TMPG 2/3 was the next most powerful independent determinant of the myocardial salvage index, and was more closely associated with higher salvage indexes than the TFGs.

Grade 0
Failure of dye to enter the microvasculature, indicating a lack of tissue level perfusion.


 * Intensity Range: 0


 * 0.5 = Minimal ground glass appearance (“blush”) or opacification of the myocardium in the distribution of the artery. Minimal blush is being defined as being either very small in size and/or being less intense or bright than “normal” blush.


 * Intensity Range: 0.5


 * Note - If no blush is present, the Qualitative Blush Analysis will all be “DNA=Does Not Apply” except for “Total Frames Elapsed in which Blush is Present” which would be “0”, “Total frames in Cinerun” and the venous system assessments.

Grade 1
Dye slowly enters, but fails to exit the microvasculature. There is ground glass appearance (“blush”) or opacification of the myocardium in the distribution of the artery that fails to clear from the microvasculature, and dye staining is present on the next injection (approximately 30 seconds between injections). Dye staining does not include arterial or venular stains. The TMPG should not be given a grade of 1 solely because either of the former are present, but only if myocardial or arteriole stains are present. There are separate fields on the CRF to note the presence of arterial/venular stains.


 * Intensity Range: 0 – 3


 * Note – If a stain is present, the blush counts can all be assessed. Quantitative blush analysis is always assessed in relation to the myocardium. For example, if the myocardium itself is stained, thus giving the cinerun a TMPG of “1”, then ignore the presence of the stain when assessing both of the following fields:


 * 1. The “Frame When Blush First Appears” should be a number >0 and should be when blush first starts to enter the myocardium, not the blush that is already present because of the stain.


 * 2. The “Total Frames Elapsed in which Blush is Present” should be the first frame in which blush is no longer present (again ignoring the stain) minus the “frame when blush first appears”.

All other counts would be assessed as normal.

Grade 2
Delayed entry and exit from the microvasculature. There is the ground glass appearance (“blush”) or opacification of the myocardium in the distribution of the artery that is strongly persistent during the washout phase (i.e. dye is strongly persistent after 3 cardiac cycles and either does not or minimally diminishes in intensity during washout).

The 3 cardiac cycles are determined from the point when dye touches either none or only one of the arterial borders (TIMI Frame 0). Strongly persistent blush at its maximum intensity is as intense/bright or more intense/bright as the fully-opacified surrounding collaterals.


 * Intensity Range: 2 - 3

Grade 3
Normal entry and exit of dye from the microvasculature. There is the ground glass appearance (“blush”) or opacification of the myocardium in the distribution of the artery that clears normally and is either gone or only mildly persistent during the washout phase (i.e. dye is gone or is only mildly persistent after 3 cardiac cycles and noticeably diminishes during the washout).

The 3 cardiac cycles are determined from the point when dye touches either none or only one of the arterial borders (TIMI Frame 0). Mildly persistent blush at its maximum intensity is not as intense or bright as the fully-opacified surrounding collaterals.

Blush which is more intense than minimal blush but less than normal blush is termed a “weak 3” and is assigned a TMPG of 3 and an intensity of 0.75.


 * Intensity Range: 0.75 – 1

Grade 2.5
Blush is present, but the distinction between TMPG 2 and TMPG 3 cannot be made due to inadequate film duration (i.e. washout not filmed). A more specific alternative to “cannot assess.”


 * Intensity Range: 1 – 2

Qualitative Blush Analysis
These counts will be in relation to the frame when contrast first enters into the artery (i.e. TIMI Frame Count).

Frame When Blush First Appears: First frame at which blush is first noticed by the quantitative angiographer in the infarct region of the myocardium (distal to the lesion or occlusion). The infarct region may be supplied by collaterals arising proximal to the lesion or occlusion.

First Frame when Blush is Brightest / Most Intense: Frame at which blush is at its peak brightness throughout the duration of the cinerun. This count should be taken at end diastole in the heart cycle, and the very first brightest.

Total Frames Elapsed in which Blush is Present: The total number of frames which blush is present in the cinerun. If filming ends before blush disappears, take total frames in cinerun and subtract the frame when blush first appears from it. If blush disappears before filming ends, it is necessary to take the frame number where it disappears and subtract the frame when blush first appears.

Total Frames in Cinerun: The number of frames from “0” to the end of the cinerun.

The frame is the venous system first appear: The frame in which the coronary sinus is first viewable to the quantitative angiographer.

TIMI Transit Classification System
Use this system for grading each type of stain(s) present.

Arterial Stain
Subclassified into 3 types:

Major Epicardial: persistence of dye in the arterial lumen of the RCA, LAD, or LCx at the time of injection.

Branch Epicardial: persistence of dye in a first order arterial branch (i.e. diagonal, septal or marginal) at the time of the next injection.

Collateral: persistence of dye in a small arteriole of 200-800 μm in diameter (not a first order branch) at the time of the next injection. In all arterial stains, the total length of dye persistence is quantified as either 1/6th, 2/6th, 3/6th, 4/6th, 5/6th, or 6/6th of the total length of the main parent vessel (from ostium to distal landmark)

Myocardial/Capillary Ground Glass Stain
Patchy: heterogeneous, blush that is composed of various and dissimilar shades of dye throughout its contiguous distribution at the time of the next injection.

Diffuse: homogenous, blush that is composed of dye that is of uniform shade throughout its contiguous distribution at the time of the next injection

In all myocardial/capillary stains, the size of the blush in the least foreshortened view in its greatest dimension is quantified as 1/3rd, 2/3rd, or 3/3rd of the total length of the parent vessel (from ostium to distal landmark)

Venular stain
Subclassified into 2 types:

Branch venular: persistence of dye in a first order branch off the coronary sinus at the time of the next injection

Coronary sinus: persistence of dye in the coronary sinus at the time of the next injection. Note: if a dye puff occurs before the filming, this could result in what appears to be coronary sinus staining. If contrast is present in the coronary sinus on the very first injection of the artery, and it is consistent throughout, it is most likely due to the dye puff.