Relationship Of Coronary Blood Flow To Clinical Outcomes

Several thrombolytic trials have demonstrated an important relationship between the different TFGs at 90 min after thrombolysis and clinical outcomes (50,75-78). The GUSTO angiographic substudy involving 1431 patients provided important insight into the mechanism linking TIMI 3 flow with reduced mortality (50). While the rate of TIMI grade 2 flow did not differ significantly among the thrombolytic regimens (25% with SK and subcutaneous heparin regimen, 28% with SK and intravenous [IV] heparin regimen, 27% with tPA and IV heparin regimen, 35% with tPA and SK combination regimen, p = NS), the rate of TIMI 3 flow was highest for the tPA with IV heparin regimen (54% compared to 29% for SK with subcutaneous heparin regimen, 32% for SK with IV heparin regimen, 38% for the tPA and SK combination regimen) (50).

The mortality rate of 7.4% for patients with TIMI 2 flow approximated that of TIMI 0 or 1 flow (mortality 8.9%) (50). In contrast, TIMI 3 flow was associated with nearly half this mortality (4.4%) (50). This trial also linked improved TIMI flow grades with improved LV ejection fractions (50). Thus, it appears that the survival benefit of front-loaded tPA (6.3% mortality as compared with 1% higher mortality with the other regimens in GUSTO) was due, at least in part, to the improved coronary blood flow (both higher patency and TIMI 3 flow rates) in the infarct-related artery with this regimen (50).

The results of GUSTO 1 raise important questions as to the potential mortality benefits that could be accrued by improved flow at 90 min following thrombolysis. An increase in the rate of TIMI 3 flow by 22% (from 32% with SK and IV heparin to 54% with front-loaded tPA) reduced the mortality by 1% (from 7.4% with SK and IV heparin to 6.3% with front-loaded tPA) in this trial (50). If there is a linear relationship, to improve mortality by yet another 1%, the rate of TIMI grade 3 flow in the infarct-related artery would need to improve by another 20% from the current mean value of 60% in all thrombolytic trials to approx 80%. The achievement of 80% rates of TIMI grade 3 flow appears to be a formidable challenge given the previous observation that there was only a 73% rate of TIMI grade 3 flow following primary angioplasty in GUSTO IIb (68).

To further evaluate the relationship between TFGs at 90 min after thrombolysis and clinical outcome, a pooled analysis of all angiographic thrombolytic trials performed to date, involving 5498 patients, is presented in Fig. 10. The 30- to 42-d mortality rate was lowest (3.7%) in patients with TIMI 3 flow at 90 min following thrombolysis and was significantly lower than that in patients with TIMI grade 2 flow (6.1%, p < 0.0001) or TIMI grade 0/1 flow (9.3%, p < 0.0001) flow (Fig. 10). The mortality rate difference between patients with TIMI 2 and 0/1 flows was also significant (p = 0.003) (Fig. 10). It is only with the larger sample size of this pooled data does the distinction between TIMI 0/1 and TIMI 2 flows become apparent. This pooled data analysis reconfirms the superiority of achieving complete reperfusion (i.e., TIMI 3 flow) after thrombolysis. Although TIMI grade 2 flow (partial perfusion) is not equivalent to TIMI 3 flow, it nevertheless confers a significant survival advantage compared with TIMI 0/1 flow and, therefore, should not be regarded as a failure of reperfusion, but rather as intermediate in benefit between TIMI grades 0/1 and 3 flows.

The assessment of the clinical significance of TIMI grade 2 flow has, however, been confounded by the tremendous interobserver variability in the visual assessment of coronary blood flow (2). In addition, TIMI grade 2 flow encompasses a wide spectrum of flows from markedly delayed to near normal flows (2). Finally, the analysis of the relationship between TIMI grade 2 flow to clinical outcomes is confounded by the observation that most of TIMI grade 2 flow is observed in LAD arteries (63%), and most of TIMI grade 3 flow has been observed in right coronary arteries (approx 75%). This statistical colinearity in infarct artery location and coronary blood flow could explain, at least in part, the significant differences in clinical outcomes (2).

The more objective CTFC is also related to clinical outcomes (79-83). In the TIMI 4, 10A and 10B trials, the flow in the infarct-related artery in survivors was significantly faster than in patients who died (CTFCs of49.5 ± 32.3, n = 1195 vs 69.6 ± 35.4, n = 53, respectively; p = 0.0003) (79). In this data set, mortality increases by 0.7% for every 10-frame rise in CTFC (p < 0.001) (79). Thus, the CTFC at 90 min following thrombolysis

Importance Timi Flow

Fig. 10. A pooled analysis of all angiographic thrombolytic trials performed to date involving 5498 patients. The 30- to 42-day mortality rate was lowest (3.7%) in patients with TIMI grade 3 flow at 90 min following thrombolysis, which was significantly lower than that in patients with either TIMI grade 2 flow (6.1%, p < 0.0001) or TIMI grade 0/1 flow (9.3%, p < 0.0001).

Fig. 10. A pooled analysis of all angiographic thrombolytic trials performed to date involving 5498 patients. The 30- to 42-day mortality rate was lowest (3.7%) in patients with TIMI grade 3 flow at 90 min following thrombolysis, which was significantly lower than that in patients with either TIMI grade 2 flow (6.1%, p < 0.0001) or TIMI grade 0/1 flow (9.3%, p < 0.0001).

would be required to increase from its current value of 35 frames to approx 21 frames (normal flow) to improve mortality by 1% (79). This is a formidable challenge given that flow in nonculprit arteries at 90 min is approx 30 frames and that culprit CTFCs following adjunctive PTCA are also approx 30 frames.

None of the patients in the TIMI studies who have had a CTFC < 14 (hyperemic or TIMI grade 4 flow) died by 30 d (79). Likewise, in the Randomized Efficacy Study of Tirofibon for Outcomes and Restenosis (RESTORE) trial (tirofiban plus heparin vs heparin alone in patients undergoing angioplasty for acute ischemic syndromes), the postangioplasty culprit flow in survivors was significantly faster than in those patients who died (CTFCs 20.4 ± 16.7, « = 1073 vs 33.4 ± 27.1, n = 10 respectively; p = 0.017) (80). Again, none of the 376 patients with a CTFC < 14 following angioplasty died in this trial, underscoring the fact that within the subgroup of patients with normal flow, there may be further subgroups with even better flow (80). The CTFC in this trial was also related to a lower rate of restenosis, even when post-procedure diameters were corrected for (81). Thus, not only is bigger better, but faster is better also (81).

We have also shown recently that slower flow distal and not proximal to the lesion is related to adverse outcomes following thrombolysis (79). Higher CTFCs are also related to increased myoglobin release (82). We have also shown that other more refined measures of coronary blood flow, such as the QCA velocity, are also related to clinical outcomes (83).

Was this article helpful?

0 0
Your Heart and Nutrition

Your Heart and Nutrition

Prevention is better than a cure. Learn how to cherish your heart by taking the necessary means to keep it pumping healthily and steadily through your life.

Get My Free Ebook


Post a comment