The Superiority of TIMI Frame Count in Detecting Coronary Flow Changes After Coronary Stenting Compared to TIMI Flow Classificat

TIMI flow grade before balloon angioplasty, after stent implantation and at control angiography at 6 months.
 Corrected TIMI frame count (CTFC) before balloon angioplasty, after stent implantation and at control angiography at 6 months.
TIMI flow class 2 and TIMI flow class 3 and CTFC. Wide overlapping of TIMI flow grade 2 and TIMI flow grade 3 between CTFC range of 30 and 69 frames. No TIMI flow grade 2 was diagnosed when CTFC was under 30 frames.
Author(s): 

Christoph Bickel, MD, H.J. Rupprecht, MD, A. Maimaitiming, MD, I. Welk, MD, S. Blankenberg, MD, F. Krummenauer, MD, J. Meyer, MD

In 1985, the Thrombolysis in Myocardial Infarction (TIMI) Study Group introduced a grading system, the TIMI Flow Classification, that categorically describes qualitative changes in coronary flow (Table 1).1 This classification, which is easy and quick to apply, is used widely not only in heart catheterization laboratories during clinical routine, but also as an endpoint in large multicenter studies (e.g., to express the 90 minute patency rates in patients treated with thrombolytics during acute myocardial infarction). In contrast to this categorical, subjective method, Gibson described a new quantitative method for assessing coronary artery flow, the TIMI Frame Count. It is a simple continuous angiographic index, which counts the number of cineframes required for contrast material to reach standard distal coronary landmarks.2 To analyze deviations between TIMI Flow Classification and TIMI Frame Count in assessing coronary flow we retrospectively examined a group of 102 patients before and after stent implantation and at the 6-month control angiography.

Methods

A retrospective analysis of the angiographic data was performed in 102 patients with coronary artery disease and an indication to percutaneous coronary intervention (77% men, 23% women) before stent implantation, after stent implantation and at 6-month control angiography (100% follow-up). Fifty-five percent of the patients had stable angina pectoris and 45% had an acute coronary syndrome. One stent was implanted in 64% of patients, while the other patients had 2 or more stents implanted; the maximum was one patient with 4 stents. The mean age of the patients was 59 years (minimum, 30 years; maximum, 80 years). The study population is described in detail in Table 2.
We assessed the TIMI flow, TIMI frame count (TFC) and the corrected TIMI frame count (CTFC) for the coronary vessel with the culprit lesion before, immediately after stent implantation and 6 months post-intervention. Coronary angiography was performed by hand injection of contrast medium via 6 French catheters and filmed at 12.5 frames/s. The original TFC is described for a cinefilm speed of 30 frames/s. To make the results of TFC analysis comparable between different studies, an adaptation to the cinefilm speed of 30 frames/s was performed as previously described.3 Therefore, the frame counts were multiplied by 2.4 (correction factor, which was calculated by the division of the cinefilm speed of 30 frames/s through the actual cinefilm speed of 12.5 frames/s). The number of cineframes required for contrast medium to reach the first standardized distal coronary landmark in the artery with the culprit lesion was measured with the frame counter on the ARRIPRO 35 cineviewer.
The analysis of the TIMI flow grade was performed following the criteria of the TIMI Study Group introduced in 1985 (Table 1). The TFCs were determined as published by Gibson 1996.2 The TFC is defined as the number of cineframes required for the contrast material to reach a standard distal coronary landmark. The first frame used for counting was the frame in which the contrast material completely entered the artery. Therefore, three conditions have to be fulfilled: 1) a column of nearly full or fully concentrated contrast material must extend across the entire width of the origin of the artery; 2) the dye must touch both borders of the origin of the artery; and 3) there must be antegrade motion of the contrast medium. If the left anterior descending coronary artery (LAD) is subselectively engaged and the left circumflex artery (LCX) is the culprit vessel, the count of TFC begins when dye first touches both borders of the LCX. The same rule holds when the LAD is the culprit vessel. That frame is defined as the last frame, where dye enters the sidebranch for the first time, which is defined as the distal anatomic landmark, instead of where the branch is completely filled with contrast medium. For the LAD, the distal bifurcation is defined as the landmark branch (“mustache”, “pitchfork”, “whale’s tale”). If the LAD goes around the apex of the heart, the branch nearest to the apex is taken. For the LCX, the frames are counted until dye enters the distal bifurcation with the longest total distance that includes the culprit lesion. For the RCA, the first branch of the posterolateral artery is defined as the distal anatomic landmark.
Because of the larger vessel length of the LAD, the TFC for coronary arteries with normal flow is different, as proven by an analysis of patients with normal coronary artery flow and their mean TFCs: LAD, 36.2 frames; RCA, 20.4 frames; and LCX, 22.2 frames.2 To adapt those differences in vessel length and to make the results of TFC comparable for the different vessels, the corrected TFC (CTFC) was introduced. The CTFC is calculated by division of the actual measured frame counts of the LAD through a correction factor of 1.7, which was calculated by the division of the mean value of LAD frame count through the mean values for RCA and LCX in a normal collective.2 The values of the frame counts for the RCA and LCX remain uncorrected. When no CTFC could be determined because the contrast medium did not reach the distal landmark, 100 frames were imputed as the value for the CTFC, as previously described.4,5
Quantitative coronary analysis was performed after balloon angioplasty, after stent implantation and at 6-month control. Angiographic pictures were projected on an ARRIPRO 35-Projector (Arnold and Richter, Munich, Germany), digitalized with a Sparc II PC with Parallax Board (Parallax, Santa Clara, California) and transferred to the AWOS-System (Siemens, Erlangen, Germany). Minimum lumen diameter of stenosis was measured.
The statistical analysis was performed either with SAS or SPSS. Graphical presentation of the data is based on box plots (SPSS) or chart diagrams done with EXCEL. Intraindividual changes in TFCs were assessed via sign rank tests (paired Wilcoxon tests). Due to the rather descriptive nature of our analyses, the resulting p-values were not formally adjusted for multiplicity. Therefore, the p-values should be regarded as descriptive measures of intraindividual trends and a p-value <= 0.05 indicates locally significant changes in TFCs.
We then categorized the TFC changes via prespecified cutpoints to make the TFC comparable to the qualitative TIMI classification. To compare the observed rates of change in both classification schemes, Cohen’s kappa is presented with its asymptotic standard error. Substantial agreement between both ratings could be established for kappa >= 0.80, sufficient agreement for at least kappa >= 0.60.

Results

The median of minimum lumen diameter of the culprit lesion before stent implantation was 0.74 mm, which increased after stent implantation to 2.63 mm and decreased after 6 months to 1.92 mm. Focusing on the differences in minimum lumen diameter before and after stent implantation in a paired analysis, an increase in lumen diameter of 1.85 mm (1.54/2.20 = 25%/75% interquartile range; p = 0.0001 in paired Wilcoxon Test) could be found. The difference in minimum lumen diameter between preinterventional and 6-month values was 1.17 mm (0.66/1.59 = 25%/75% interquartile range; p = 0.0001 in paired Wilcoxon Test), an effective increase in lumen diameter which is still highly statistically significant.
The analysis of TIMI flow grades (Figure 1) demonstrated that 20% of the patients had a totally occluded vessel preintervention. A TIMI flow grade 1 was seen in 5%, grade 2 in 13% and grade 3 in 63%. After stent implantation, no patient had TIMI grade 0 flow and 1 patient had TIMI grade 1 flow. Postintervention, 99% of the patients had TIMI grade 2 or 3 flow. At the 6-month control angiography, 4% of the patients had TIMI grade 0 or 1 flow, while 96% of the patients had TIMI grade 2 or 3 flow.
The median of the CTFC values was 43.2 frames (26.4/100.0 = 25%/75% interquartile range) before stent implantation, 16.9 frames (14.4/31.1 = 25%/75% interquartile range) after stent implantation and 21.6 frames (16.8/32.5 = 25%/75% interquartile range) after 6 months. Increasing coronary flow after stent implantation becomes evident by the value of -19.2 frames for CTFC differences before and after stent implantation (-52.8/-8.47 = 25%/75% interquartile range; p = 0.0001 in paired Wilcoxon Test). After 6 months, a difference in CTFC compared to the preinterventional point of time of -16.8 frames (-48.0/-4.8 = 25%/75% interquartile range; p = 0.0001 in paired Wilcoxon Test) was determined. The preinterventional CTFC values showed a bimodal, not a normal distribution with a peak of values between 20 and 29 frames and a second peak over 100 frames (Figure 2). After stent implantation, an unimodal left-skewed distribution of CTFC values was observed. The maximum of CTFC values was reached earlier between 10 and 19 frames. After stent implantation, the peak of CTFC values ranged again between 10 and 19 frames, but the intracoronary flow was again reduced as expressed by higher frame counts.
A comparison of CTFC values for patients with TIMI flow grade 3 and TIMI flow grade 2 showed an overlap between 30 and 69 frames (Figure 3). No patients were found with TIMI flow grade 2 under 30 frames or with TIMI flow grade 3 over 70 frames.
We also investigated whether or not CTFC changes (> 5 frames) and TIMI flow changes were both able to detect an alteration of intracoronary flow (Tables 2 and 3). CTFC is able to find more flow changes than TIMI Flow Classification. Comparing preinterventional versus postinterventional or postinterventional versus 6 months results, CTFC detected intracoronary flow changes in 46% and 39% of the patients, which were not detected by TIMI Flow Classification. Corresponding results were obtained for rather sensitive cutpoints of > 10 and > 15 frames (data not shown).

Discussion


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