Elsevier

American Heart Journal

Volume 137, Issue 6, June 1999, Pages 1179-1184
American Heart Journal

Methodologic drift in the assessment of TIMI grade 3 flow and its implications with respect to the reporting of angiographic trial results,☆☆

https://doi.org/10.1016/S0002-8703(99)70380-7Get rights and content

Abstract

Background The Thrombolysis In Myocardial Infarction (TIMI) Study Group originally defined TIMI grade 3 flow (complete perfusion) as antegrade flow into the bed distal to the obstruction that occurs as promptly as antegrade flow into the bed proximal to the obstruction. Recently, several groups have defined TIMI grade 3 flow as opacification of the coronary artery within 3 cardiac cycles. Methods and Results On the basis of heart rate data at the time of the cardiac catheterization and the time for dye to go down the artery (TIMI frame count/30 = seconds), we estimated the number of patients who would meet the 3 cardiac cycle criterion and compared this with the number of patients with TIMI grade 3 flow by using the original definition in 1157 patients from 3 recent TIMI trials (10 A, 10B, and 14). In 74 patients without acute myocardial infarction and normal coronary arteries, the fraction of a cardiac cycle required for dye to traverse the artery was a mean of 0.93 ± 0.34 cardiac cycles (n = 74) (median 0.80, minimum 0.44, maximum 2.1, none >3.0 cycles). The mean heart rate at 90 minutes after thrombolysis in the TIMI 14 trial was 79.6 ± 16.8 beats/min (n = 194), and the duration of 3 cardiac cycles was a mean of 2.36 seconds, or a TIMI frame count of 70.8 frames. In all trials, the rate of TIMI grade 3 flow was 57.3% (n = 663/1157) with the original definition and 66.8% (n = 743/1113) with the <3 cardiac cycle definition (P < .001). Conclusions A duration of 3 cardiac cycles for dye to traverse the artery lies approximately 6 SD above that observed in normal coronary arteries. A 3 cardiac cycle definition of TIMI grade 3 flow results in rates of normal perfusion that are approximately 10% higher than if the original definition of TIMI grade 3 flow is applied. Application of this simple correction factor may help place data reported with the 3 cardiac cycle definition of TIMI grade 3 flow in context. (Am Heart J 1999;137:1179-5.)

Section snippets

Methods

The data are drawn from 3 recent TIMI trials: TIMI 10A, 10B, and 14. TIMI 10A was a nonrandomized, open-label, dose escalation study of 8 ascending doses of TNK (5, 7.5, 10, 15, 20, 30, 40, and 50 mg given intravenously over 5 to 10 seconds) in 113 patients.4 TIMI 10B was a randomized trial of 30-, 40-, and 50-mg doses of TNK versus front-loaded recombinant tissue plasminogen activator (r-TPA) in 853 patients.5 TIMI 14 is a trial of abciximab alone versus abciximab in combination with low-dose

Results

To place the rate of TIMI grade 3 flow reported by the TIMI angiographic core laboratory in context, a pooled analysis involving 1492 patients from angiographic trials of front-loaded TPA reported to date reveals an overall 90-minute patency rate of 82% (60% rate of TIMI 3 flow and 22% rate of TIMI 2 flow),6, 10, 11, 12, 13, 14, 15, 16 as shown in Figure 1.

. Rate of TIMI grade 3 flow varies significantly for same drug (front-loaded TPA) across trials. Pooled analysis involving 1492 patients from

Discussion

We have shown that even when the same definition is applied by angiographers, there is a substantial interobserver variability in the classification of the TIMI flow grades.7 The rate of agreement between an angiographic core laboratory and clinical centers is good in determining whether a culprit artery is either open or closed (κ = 0.84).7 In contrast, the rate of agreement is only moderate when assessing TIMI grade 3 flow (κ = 0.55) and is actually poor in the assessment of TIMI grade 2 flow

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    Reprint requests: C. Michael Gibson, MS, MD, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212.

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