TIMI flow grade
The TIMI flow grades were recorded as values between 0 and 3 (Chapter 1, Table 1.1).26
TIMI thrombus grade
TIMI thrombus grade was measured using the grading system originally developed by the TIMI study group (Chapter 1, Table 1.3).94 To measure thrombus burden, I used the cinerun that displayed the first time-point at which dye flows distal to the occlusion. This view ensured the thrombus was fully visualised because the flow of contrast was able to outline the full mass before the thrombus was likely to be dislodged from the vessel wall.
Displacement of the thrombus normally occurs after initial wire insertion or balloon dilatation of the culprit vessel. If initial wiring or ballooning did not allow blood flow distal to the thrombus, and the vessel remained totally occluded, then the thrombus burden was graded 5: total occlusion. If thrombus aspiration was performed, the thrombus burden was graded in the cinerun before thrombus aspiration. The thrombus burden was graded using a measuring tool within the angiogram viewing software (Figure 2.1). The size of the thrombus was measured relative to the vessel diameter, allowing calculation of the ratio of thrombus length to vessel diameter and an assessment of thrombus burden (Figure 2.2). A change in the angiographic projection angle can make a linear mass appear shorted. This can be a source of error. For consistency, measurements of thrombus were made from the view where the thrombus appeared to have the longest length.
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Figure 2.1: The measuring tool within the angiogram viewing software, Xcelera, used to measure the length of thrombus burden in the culprit artery
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Figure 2.2: Using the measuring tool in Xcelera to compare the length of thrombus with the diameter of the culprit vessel to grade the thrombus burden
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Figure 2.3: A: Frame -1, before dye injection B: Frame 0, dye has reached both sides of the vessel but there is no evidence of antegrade flow. C: Frame 1, there is clear demarcation
of the vessel walls and evidence of antegrade flow. This is the initial frame. Corrected TIMI Frame Count (cTFC)
Corrected TIMI frame count (cTFC) was calculated using the method described in the TIMI 4 trial.99 The cTFC estimates the speed of contrast moving down the coronary artery by counting the number of cineframes required for contrast to reach standardised distal coronary landmarks.
Selecting the initial frame for cTFC
The first frame used to calculate cTFC was the frame in which dye first fully enters the culprit artery after injection of contrast. This was defined when three criteria were met (Figure 2.3):
• A column of nearly full or fully concentrated dye must extend across the entire width of the origin of the artery.
• Dye must touch both borders of the origin of the artery. • There must be antegrade motion to the dye
If the location of the vessel walls was not clear, then the frame where the width of dye across the vessel is at a maximum was used.
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If the LAD was subselectively engaged and the circumflex was being assessed, the first frame was counted from when the dye first touches both borders of the Cx.
Selecting the final frame for cTFC
The last frame was counted when dye first entered the distal landmark branch. Full opacification of the branch was not required; the initial opacification of the branch was counted as the final frame.
The distal landmark branches used for analysis:
• LAD: the distal bifurcation (i.e. the “pitchfork” or “whale’s tail”) (Figure 2.4 – image reproduced with permission – see Appendix 2).
• Circumflex: distal bifurcation of the segment with the longest total distance. If the circumflex was the culprit artery, then the longest distance that includes the culprit lesion was used (Figure 2.4).
• Right coronary artery: the first branch arising from the posterior lateral extension of the RCA after the origin of the posterior descending artery
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Figure 2.4: Anatomical landmarks used for TIMI frame counting in LAD and Cx vessels
For the final frame, the branch used must be present for more than one consecutive frame. This ensures that it is not a branch from another vessel (overlapping the region of interest) or artefact. To identify the final frame in all vessels except the RCA (and branches arising from the RCA), I used the branch that appears most distally along the vessel or on the vessel closest to the apex in the LAD. If a proximal branch fills after the most distal branch, then we used the proximal branch. This is because I was trying to measure the speed of blood flow and extent of myocardial perfusion, therefore the last vessel to fill should be the
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final frame as this will give an approximation of the time taken to fill the smaller vessels and microvasculature.
Optimum angiographic views for assessing cTFC
When choosing the correct angiographic image to use for assessing the cTFC, circumflex vessels were best assessed in the right or left anterior oblique views with caudal angulation whereas the LAD was best assessed with cranial or lateral angulation. The RCA was best assessed in the left anterior oblique projection with steep cranial angulation.
Correcting for vessel length when assessing cTFC in the LAD.
The frame count does not differ significantly between the RCA and circumflex. However, the frame count in the LAD was significantly increased because the LAD is longer in length than the RCA or circumflex. Therefore, the frame count measured for the LAD was divided by 1.7 to calculate the final cTFC.
cTFC in wraparound LADs
A proportion of LAD arteries wrapped around the apex of the heart. When measuring the TFC in such vessels the aim was to measure the final frame at the frame contrast enters the branch that occurs closest to the apex. This vessel is best chosen by drawing a straight line from the ostium of the LAD to the apex and choosing the vessel closest to the line (Figure 2.5).
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Figure 2.5: Selecting the branch closest to the apex for establishing the final frame for cTFC assessment of the LAD
Estimating cTFC when the full length of a vessel is not visualised
Some angiograms did not visualise the full length of the culprit vessel. In these cases, the vessel length was estimated based on looking at the length of the vessel in other runs and the cTFC was measured based on the visible fraction of the vessel on the angiogram. The cTFC was then estimated for total length of the vessel giving the “estimated cTFC.”
Intermediate and diagonal culprit arteries
CTFC in intermediate and diagonal arteries was measured using the same method as in the circumflex artery: I counted the number of frames until contrast reached the most distal
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bifurcation. If the culprit was the diagonal artery, the initial frame was counted from the ostium of the LAD.
Posterior left ventricular artery culprit
If the culprit lesion was the posterior left ventricular (PLV) artery, I recorded the final frame as the frame where the first branch of the PLV after the culprit lesion first appeared. The original method of measuring cTFC in the RCA specifies counting cTFC to the first branch after the origin of the PDA. If the culprit is the PDA or interventricular branch, then the branch immediately distal to the culprit branch was used.
Frame speed
The cTFC is designed for angiograms acquired at 30 frames per second. Some angiograms during PPCI were acquired at 15 frames per second. To ensure the correct value for TFC was recorded, the number of frames counted was corrected for the frame rate, using 30 frames per second as the standard.
cTFC in an occluded culprit
If the culprit vessel was occluded, then the cTFC could not be calculated and the corresponding database field was left blank.
Use of nitrates
In HEAT-PPCI, the use of nitrates was not recorded, therefore cTFC was not corrected for nitrate use, as suggested in the original method.
65 Myocardial Blush Grade (MBG)
The MBG was calculated by examining the flow of contrast into the myocardium perfused by the culprit artery (either right or left), using the method developed by van’t Hof et al.104 Figure 2.6 illustrates an example of normal myocardial blush in the RCA.
Figure 2.6: Normal grade 3 myocardial blush is demonstrated in the RCA. The region of myocardial blush is ringed in red in the right-hand image
Myocardial blush was graded as normal (grade 3) if the density of contrast appearing in the myocardium perfused by the culprit was equal to the density observed in the non-culprit side. If the density was less in the culprit side than the non-culprit side, MBG was graded as 1 or 2, according to the definitions in Chapter 1, Table 1.4. If no contrast appeared in the culprit side, MBG was graded 0. The run with the best projection was chosen to assess the myocardial region of the infarct-related coronary artery. Angiographic runs had to be sustained for long enough to allow some filling of the venous system. Backflow of contrast into the aorta should be present to be sure of adequate contrast filling into the epicardial coronary artery. If these criteria were not met, the MBG could not be calculated and the
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corresponding database field was left blank. If myocardial blush is present before the injection of contrast, also known as “staining”, this was noted in the study database.
The method developed by van’t Hof et al. to assess the MBG involved all patients receiving the same dose of intracoronary nitroglycerin. In HEAT-PPCI there was no standardization of administration of IC nitroglycerin which may have affected the MBG grade.
Limitations
In the initial testing phase, I attempted to measure the grading systems as they were described in the literature. I found the original methods lacked detail to allow analysis of all angiograms in the HEAT-PPCI trial. I addressed these issues at the core lab and adopted their specific and proven methods of angiographic assessment. However, because the core labs do not publish their own methods of angiogram analysis there is likely to be variability between core labs as well as between research teams using these grading systems. A comprehensive method of assessing the grading systems should be published by the core labs to ensure the grades are comparable when used in different studies.
The accuracy of measurements is likely to differ across angiograms of varying quality. Our data was collected retrospectively, and the angiograms used were not obtained for the purpose of assessing the selected grading systems. In some cases, I was unable to assess a grading system because of poor angiographic quality. PPCI angiograms tend to be of poorer quality than those used in stable disease and this may impact the reproducibility of our methods between observers in the PPCI setting. I address the interobserver variability of the angiographic grading systems in Chapter 6.
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