Author + information
- Received March 10, 2010
- Revision received September 10, 2010
- Accepted September 17, 2010
- Published online January 1, 2011.
- Marco Valgimigli, MD, PhD⁎,†,⁎ (, )
- Gianluca Campo, MD⁎,
- Patrizia Malagutti, MD⁎,
- Maurizio Anselmi, MD‡,
- Leonardo Bolognese, MD§,
- Flavio Ribichini, MD‡,
- Giacomo Boccuzzi, MD∥,
- Nicoletta de Cesare, MD#,
- Alfredo E. Rodriguez, MD, PhD§§,
- Filippo Russo, MD⁎⁎,
- Raul Moreno, MD∥∥,
- Giuseppe Biondi-Zoccai, MD¶,
- Carlo Penzo, MD††,
- José F. Díaz Fernández, MD¶¶,
- Giovanni Parrinello, PhD‡‡ and
- Roberto Ferrari, MD, PhD⁎,†
- ↵⁎Reprint requests and correspondence:
Dr. Marco Valgimigli, Cardiovascular Institute, Azienda Opedaliera Universitaria di Ferrara, and Corso Giovecca 203, 44100 Ferrara, Italy
Objectives These studies sought to investigate the impact on mortality of coronary flow after passage of the wire through the culprit vessel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical reperfusion.
Background Reduced spontaneous coronary flow before percutaneous coronary intervention influences mortality in patients with STEMI. Response to vessel wiring in patients with an occluded coronary artery before intervention might further discriminate outcomes irrespective of pre- and post-intervention coronary flow.
Methods Data from the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials were pooled: of 919 index procedures, 902 films (98%) were technically adequate for core laboratory TIMI (Thrombolysis In Myocardial Infarction) flow determination.
Results TIMI flow grade 0 was present before percutaneous coronary intervention in 59% of infarct vessels, TIMI flow grade 1 to 2 was found in 21%, whereas the remainder of infarct arteries presented with TIMI flow grade 3. In 49% of patients who showed persistent TIMI flow grade 0 after wire insertion (AWI), mortality was higher at 30 days (5.3%) and 1 year (9.4%) compared with patients in whom TIMI flow grade before percutaneous coronary intervention was either >0 (0.8%; p < 0.003 and 3.6%, p < 0.008) or improved from 0 AWI (1.5%, p < 0.04 and 3.6%, p < 0.02). After correcting for multiple imbalances, including baseline and final flow, persistent TIMI flow grade 0 AWI remained associated at 30 days to 2-fold (risk ratio [RR]: 2.1, 95% confidence interval [CI]: 1.08 to 5.00; p = 0.038) and at 1 year to almost 3-fold increases of mortality (RR: 2.7, 95% CI: 1.3 to 5.6; p = 0.008).
Conclusions STEMI patients displaying persistent no-flow AWI have a lower survival rate despite an apparently successful mechanical intervention. As an early marker for high residual mortality risk, persistent no-flow AWI may qualify STEMI patients for dedicated pharmacomechanical treatment strategies.
Coronary flow before intervention, graded semiquantitatively according to the TIMI (Thrombolysis In Myocardial Infarction) angiographic scale, has been previously shown to influence short- (30 days) and medium-term (6 months) mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) (1,2). Importantly, the independent effect of initial flow in the culprit coronary artery on survival persisted even after correction for post-procedural flow (1), which suggests that early pre-PCI reperfusion has salutary benefits independent of promoting ultimate restoration of TIMI flow grade 3 (2). Early pre-PCI reperfusion may improve survival by enhancing myocardial recovery and/or by optimizing procedural success, of which final TIMI flow grade 3 is known to be a rather insensitive surrogate marker (3–7). A prognostic indicator for high residual mortality risk despite successful mechanical intervention in STEMI patients would be desirable to tailor intensity/complexity of treatment accordingly.
We hypothesized that in patients presenting with occluded coronary artery before intervention, for whom prognosis is known to be unfavorable (1,8), response to vessel instrumentation through passage of the wire may further discriminate outcomes compared with both pre- and post-PCI coronary flow.
Data from 2 trials—STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) (9) (n = 175) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) (10) (n = 745)—were pooled in a computerized database. The major entry criteria of these trials were similar and deliberately nonrestrictive: 74% of all-comer patients who presented to the study sites with STEMI during recruitment period were included. The inclusion criteria were: 1) chest pain for >30 min with an electrocardiographic ST-segment elevation ≥1 mm in 2 or more contiguous electrocardiogram leads, or with a new left bundle-branch block; and 2) admission either within 12 h of symptom onset or between 12 and 24 h after onset with evidence of continuing ischemia. The exclusion criteria included administration of fibrinolytics in the previous 30 days, major surgery within 15 days, and active bleeding or previous stroke in the last 6 months. Moreover, for both trials, to minimize the potential for angiographic selection bias, protocols mandated inclusion of patients immediately after clinical eligibility criteria were met and before the visualization of coronary arteries through angiography (9,10). Follow-up visits were scheduled for the STRATEGY trial at 1, 6, and 12 months and at 1, 4, 8, and 12 months for the MULTISTRATEGY trial.
Study medications and intervention
At presentation, patients from both studies received aspirin (160 to 325 mg orally or 250 mg intravenously, followed by 80 to 125 mg orally indefinitely) and clopidogrel (300 mg orally and then 75 mg/day for at least 3 months). Heparin was given during transportation to the primary PCI facility or just in the catheterization laboratory at 40 to 70 U/kg, targeting an activated clotting time of at least 200 s. Before arterial sheath insertion, patients in both studies were randomly allocated with a 1:1 ratio to receive tirofiban, which was given as a bolus of 25 μg/kg, followed by an 18- to 24-h infusion at 0.15 μg/kg/min or abciximab, which was administered as a bolus of 0.25 mg/kg, followed by a 12-h infusion at 0.125 μg/kg/min. As part of a pre-specified subanalysis of both trials, the STRATEGY and MULTISTRATEGY protocols mandated acquisition of a coronary angiogram using the standard frame rate immediately after passage of the wire distal to the lesion to allow for central adjudication of TIMI flow grade after wire insertion (AWI) by an independent core laboratory. Stenting was the default strategy in patients with a reference vessel diameter ≥2.5 mm at visual estimation. Patients were randomized in both studies to sirolimus-eluting stent or any uncoated-stent type approved by the regulatory agency. The use of pre- or post-dilation and thrombus aspiration was left to the discretion of the treating physician.
Definitions and statistical analysis
Study end point definitions have been previously reported (9–11) and were consistent throughout the 2 studies. All events in each study were reviewed by an independent adjudication committee up to 1-year follow-up. Blood flows in the infarct vessel at baseline, after passage of the wire, and at the end of intervention were evaluated with the TIMI scale at a single independent core angiographic laboratory for both studies (Medical Trial Analysis, Ferrara, Italy).
In particular, TIMI flow grade 0 was defined as complete vessel occlusion with no angiographic visualization of the vessel beyond site of stenosis, whereas TIMI flow grade 3 was defined as complete filling of the distal vessel by the third cardiac cycle.
Per protocol in both studies, investigators were asked to film coronary flow before (pre-PCI flow) and immediately after wire insertion (TIMI AWI), which was defined as satisfactory positioning of the wire completely down the length of the infarct artery, and upon removal of wire after intervention (post-PCI flow).
Categorical variables were compared by chi-square analysis or Fisher exact test. Continuous variables are presented as mean ± SD and were compared by Student t test or analysis of variance (ANOVA), whereas post hoc comparisons were performed by Tukey honest significance difference test. To test for heterogeneity between the 2 included studies, 3 approaches were carried out: 1) the Q-statistic was computed for the hazard ratios for mortality in patients with persistent occluded coronary artery after the wire in the 2 studies (I2 = 0; p = 0.99); 2) the Q-statistic was computed for the hazard ratios for mortality in patients with persistent occluded coronary artery after the wire across different sites (n = 16) that participated in the MULTISTRATEGY trial (I2 = 0; p = 0.78); and 3) we compared by likelihood-ratio test 2 models originated by including or excluding the interaction treatment by study and confirmed that the 2 log-likelihoods of the regression models were not improved by adding an interaction term (p > 0.99).
After pooling of data, given the absence of heterogeneity, the incidence of events over time was studied by the Kaplan–Meier method, and log-rank tests were applied to evaluate differences between patients based on coronary flow graded semiquantitatively according to the TIMI angiographic scale. To assess the independent role of baseline TIMI flow grade on mortality, the following variables were introduced into the Cox proportional hazards model (Cox-model 1): sex, heart rate, Killip class, culprit vessel, total stent length, maximal stent size, direct stenting, time from drug bolus to first balloon inflation, TIMI flow grade at baseline (coded as 0 vs. the others) and final TIMI flow grade (coded as 3 vs. the others), cumulative ST-segment elevation at electrocardiogram, and left ventricular ejection fraction at discharge. Scaled Schoenfeld residuals were used to verify the assumption of proportionality.
To further evaluate the prognostic value of TIMI flow grade 0 after insertion of the wire, all variables included in Tables 1 and 2⇓ as well as cumulative ST-segment elevation before PCI and left ventricular ejection fraction at discharge were tested as univariate predictors of 30-day or 1-year mortality at Cox proportional hazards model (Cox-model 2). Given the limited numbers of events in relation to the number of the studied parameters, a variable selection using the Akaike information criterion was performed, followed by a bootstrapped variance estimation to avoid overfitting (12).
Two independent sensitivity analyses were carried out to assess the robustness of Cox-model 2: 1) a Cox proportional hazards model (Cox-model 3) including all variables included in Cox-model 1 plus active smoking status, creatinine clearance, total ischemic time and stent post-dilation; and 2) the random survival forest model, which has the advantage to adapt to the data and is virtually model assumption free (13).
The increased discriminative value of adding TIMI AWI was further examined with the method described by Pencina et al. (14). This method is based on the difference between 2 models in the individual estimated probability that a case subject will be categorized as a case subject. An increased probability that case subjects will be categorized as case subjects and a decreased probability that control subjects will be categorized as case subjects imply better prediction ability, whereas the opposite implies worse prediction ability.
The net reclassification improvement method requires that there exist a priori meaningful risk categories for the risk of death from cardiovascular causes, whereas the integrated discrimination improvement considers the change in the estimated prediction probabilities as a continuous variable.
All tests are 2-sided with a significance level of 0.05. All statistical analyses were performed using Stata (version 9.2, Stata Corp., College Station, Texas) and using the random forest as given in the R library (15).
Of 919 index procedures, 902 films (98%) were technically adequate for core laboratory TIMI flow grade determination. TIMI flow grade 0 was present before PCI in 58.9% of infarct vessels, suboptimal flow (TIMI flow grade 1 to 2) was found in 21.4%, whereas the remainder of infarct arteries presented with TIMI flow grade 3.
Compared with patients with TIMI flow grade >0 at baseline, patients with occluded artery before PCI had lower heart rate, were more likely to be in Killip class greater than 1, and the right coronary artery was less likely to be the infarcted vessel (Table 1). They were also more likely to undergo multiple stenting with a final greater stent length and receive shorter pre-treatment duration with glycoprotein IIb/IIIa inhibitors before angiogram (Table 2).
Among patients with baseline TIMI flow grade 0, those in whom the culprit artery remained totally occluded AWI were less frequently smokers, had lower creatinine clearance, longer durations of symptoms, and underwent stent post-dilation less often compared with patients who improved TIMI flow grade after passage of the wire (Tables 1 and 2).
Impact of baseline TIMI flow grade on final TIMI flow grade
As shown in Figure 1, final normal TIMI flow grade was reached in 96% to 97% of patients presenting with TIMI flow grade >0 and in 92% of patients with occluded artery at baseline. Interestingly, in the latter group, final TIMI flow grade 3 was successfully established in 96% of patients who improved TIMI flow grade after the wire and in only 89% of those in whom no-flow was still present after the vessel wiring. However, none of these differences reached statistical significance.
TIMI flow grade, cumulative ST-segment elevation, and left ventricular ejection fraction
Cumulative ST-segment elevation at transthoracic electrocardiogram immediately before mechanical intervention differed based upon coronary TIMI flow grade at first angiogram (p < 0.002 at ANOVA). Post-hoc analysis revealed that it was higher in both TIMI flow grade 0 (11.7 ± 8.5 mm) and TIMI flow grade 1 (13 ± 9 mm) groups compared with that observed in TIMI flow grade 3 patients (9.2 ± 7.9 mm, p < 0.002 for both) (Fig. 2A). Left ventricular ejection fraction at discharge also varied across patients stratified according to coronary flow before intervention (p < 0.0003 at ANOVA), with those presenting with either TIMI flow grade 0 (48.2 ± 10%) or flow grade 1 (46.7 ± 9%) showing lower ejection fractions than individuals with TIMI flow grade 3 (51.8 ± 10, p < 0.003 for both at post hoc analysis) (Fig. 2A). Focusing on patients with TIMI flow grade 0 before intervention, cumulative ST-segment elevation did not differ in patients with persistent no-flow compared with those who had TIMI flow grade >0 AWI (12 ± 9 vs. 11.5 ± 7.9, respectively; p = 0.46 at post hoc analysis) (Fig. 2B). However, patients presenting with TIMI flow grade 0 who improved coronary flow after passage of the wire had significantly higher left ventricular ejection fraction at discharge (50 ± 9%) compared with those in whom no flow improvement after the wire was noted (46.4 ± 10%, p = 0.004 at post hoc analysis) (Fig. 2B). Interestingly, left ventricular ejection fraction in patients with baseline TIMI flow grade 0 yet with TIMI flow grade >0 AWI did not differ compared with patients with TIMI flow grade 3 before intervention (Fig. 2B). A similar pattern has also been noted for the cumulative ST-segment elevation resolution stratified based on pre-PCI TIMI flow grade (p < 0.0001 at ANOVA) (Fig. 2C). Patients with TIMI flow grade 0 at baseline who improved coronary flow AWI reached similar ST-segment resolution after intervention compared with patients with spontaneous TIMI flow grade 3 before PCI (Fig. 2C).
Impact of baseline TIMI flow on 30-day and 1-year outcomes
Table 3 shows outcomes at 30 days and 1 year stratified according to TIMI flow grade in the culprit vessel at baseline. Mortality at 30 days was higher in patients with TIMI flow grade 0 than in remainder patients, whereas it did not differ further in patients with nonoccluded vessel at baseline. At 1 year, mortality was still twice as high as for patients with nonoccluded artery at baseline, but this difference failed to reach statistical significance at univariate analysis. After correcting for multiple clinical and angiographic imbalances, including final TIMI flow grade 3, the presence of TIMI flow grade 0 before intervention was an independent and more powerful predictor of 30-day (risk ratio [RR]: 5.2, p = 0.032) and 1-year (RR: 2.1, p = 0.031) survival than TIMI flow grade 3 after intervention (RR: 2.67, p = 0.13, and 1.5, p = 0.39, respectively).
Impact of no-flow after the wire on 30-day and 1-year survival
As shown in Table 3, the capability of TIMI flow grade 0 at baseline to predict higher mortality rate at 30 days and 1 year was almost entirely attributable to no flow pattern AWI. Thirty-day and 1-year mortality in patients with no flow at baseline, who responded to vessel wiring with an improvement of TIMI flow grade, were similar to patients with nontotally occluded artery before any intervention (Fig. 3A). At stratified analysis, persistence of no-flow AWI was still able to identify patients at increased risk of 1-year mortality after exclusion of those with suboptimal (TIMI flow grade <3) coronary flow after intervention (Fig. 3B). Multivariable analysis including both TIMI flow grade before and after intervention showed that TIMI flow grade 0 AWI remained associated with 2-fold increase of mortality at 30 days (RR: 2.1, 95% confidence interval [CI]: 1.08 to 5; p = 0.038) and almost 3-fold increase of mortality at 1-year (RR: 2.7, 95% CI: 1.3 to 5.6; p = 0.008) (Table 4). The independent value of TIMI flow grade 0 AWI on mortality was confirmed at sensitivity analyses (data not shown).
The net reclassification improvement was estimated at 0.556 (p < 0.001) after the addition of TIMI AWI, whereas the integrated discrimination improvement was estimated at 0.038 (p = 0.005).
The main findings of our analysis can be summarized as follows:
1. TIMI flow grade before the procedure in patients undergoing mechanical intervention was confirmed to be an independent predictor of poor survival even when corrected for post-procedural flow. In particular, patients with TIMI flow grade 0 at baseline were at higher risk for short- and long-term mortality independently from final achievement of TIMI flow grade 3, whereas outcomes did not further differ based on the adequacy of angiographically determined antegrade coronary flow pre-PCI.
2. Response to the passage of the wire through the culprit lesion further discriminated outcomes in patients with totally occluded artery at baseline. Patients with baseline TIMI flow grade 0 in whom coronary flow AWI improved had a fairly good prognosis, with mortality rate in the range of 1.5% and 3.5% at 30 days and 1 year, respectively, which did not differ from the patients with nonoccluded artery before intervention. On the contrary, in 49% of patients with baseline occluded coronary artery in whom passage of the wire failed to restore some antegrade coronary flow (roughly representing 30% of the original cohort of patients), mortality rate was remarkably higher, in the range of 5% at 30 days and 9% at 1 year, which was not explained by final TIMI flow grade nor by other clinical and angiographic baseline features.
Brodie et al. (2) first reported a different survival pattern in patients presenting with TIMI flow grade 2 or 3 before intervention as opposed to patients with baseline TIMI flow grade 0/1.
Subsequently, in the pooled analysis of the PAMI (Primary Angioplasty in Myocardial Infarction) trials, there appeared to be a continuum of risk at univariate analysis based on initial TIMI flow grade with mortality at 6 months being 4.4% in patients with initial TIMI flow grade 0/1, 2.8% in TIMI flow grade 2, and 0.5% in TIMI flow grade 3 patients (1). However, early reperfusion with initial TIMI flow grade 3 only emerged as independent predictor of in-hospital and medium-term mortality after adjustment for confounders (1). This landmark finding led to the convincing argument that early pharmacological strategies facilitating mechanical intervention had to increase the rate pre-procedural TIMI flow grade 3 to significantly improve outcomes, emphasizing the primacy of the “open-artery hypothesis.”
As a result, trials have been designed to test the early initiation of various antithrombotic strategies primarily aimed at increasing the rate of TIMI flow grade 3 before intervention (16).
Our findings expand on that and suggest that the presence of at least some anterograde coronary flow before intervention might be likewise beneficial in short- and long-term survival in patients ultimately undergoing emergent mechanical intervention. The reasons for our results being apparently discrepant with respect to the pooled analysis of the PAMI trials are unclear. It should be noted that by protocol, patients in our study had to receive either tirofiban or abciximab before arterial sheath insertion, whereas the use of glycoprotein IIb/IIIa inhibitors was marginal (∼3%) in the PAMI trials (1). Similarly, patients had to receive clopidogrel beyond aspirin and unfractionated heparin at first medical contact, whereas ticlopidine was given in the emergency department only in the PAMI Stent Pilot (17) and Randomized (18) trials. The more potent and contemporary antiplatelet environment in which mechanical intervention has been carried out in our study versus the PAMI trials may facilitate myocardial recovery and/or optimize myocardial microcirculation and thus make procedural success less dependent on optimal spontaneous flow before intervention. In keeping with our results are recent randomized or registry studies on facilitated PCI, where: 1) enhancing platelet inhibition with various drugs resulted in an improved outcome that was paralleled by an overall improvement of vessel recanalization (TIMI flow grade ≥1) but not necessarily by a clear increase in the rate of TIMI flow grade 3 before intervention (6,19–21); and 2) the presence of at least some pre-procedure TIMI flow grade >0 (8) or ≥2 (21) was the only/most important predictor of left ventricular function recovery after intervention.
Our study also provides evidence that response to vessel wiring, the initial mandatory step to provide mechanical intervention, may allow us to further discriminate outcome in patients who presented with occluded coronary artery, with an adjusted almost 3-fold increase in overall mortality at 1 year in patients with persistent no-flow after positioning of the wire along the infracted artery. Although the mechanisms of this finding cannot be determined with certainty by the present study, patients with no-flow AWI had similar extension of the ischemic area based on cumulative ST-segment elevation, yet they tended to have a lower rate of final TIMI flow grade 3, a suboptimal ST-segment elevation resolution after intervention, and a more depressed left ventricular ejection fraction at discharge than did patients with totally occluded artery at baseline who had improved flow AWI. Thus, an improvement of coronary flow AWI in patients with totally occluded infarcted artery before intervention may predict an improved procedural success and myocardial function recovery, which provides a mechanistic explanation for the benefits seen in this patient population.
Patients in whom passage of the wire is sufficient to improve antegrade coronary flow may have lower residual thrombus burden, less distal microvascular obstruction, or improved technical success from the advantages of initial lesion delineation and road-mapping. This hypothesis is indirectly supported by the observation that direct stenting was more frequently applied and that stent post-dilation, which may frequently trigger slow- or no-flow in the setting of heavily thrombotic environment, was less frequently performed in patients with no-flow AWI. Importantly, however, neither direct stenting nor stent post-dilation had any impact on short-term or 1-year outcomes in our multivariable model. Although the presence of thrombus did not differ in patients with or without wire-induced vessel recanalization, angiography is known to be an insensitive tool to detect and quantify coronary thrombus (22) and, importantly, does not provide information on thrombus stability to mechanical disruption. Interestingly, patients with no-flow AWI were more likely to receive intervention beyond the 3-h window. Indeed, coronary thrombus organizes over time (23) and becomes more resistant to both pharmacological and mechanical fragmentation. Thus, TIMI flow grade 0 AWI may constitute a readily available angiographic marker for partially organized, more resistant coronary thrombus, which may hamper optimal myocardial reperfusion under standard care.
Interestingly, Burzotta et al. (24) found manual thrombectomy to be particularly useful in patients with persistent occluded artery after the wire, which may support the concept that thrombus removal, more than mechanical dislodgement or pharmacological dissolution, may be especially useful in this subset of patients. Importantly, the use of thrombus aspiration devices was equally distributed among the various patterns of TIMI flow grade at baseline or AWI reported in our pooled analysis. Thus, it remains possible and worth being further explored that a more systematic use of thrombectomy in patients with TIMI flow grade 0 AWI may optimize procedural success beyond the achievement of final TIMI flow grade 3 and ultimately mitigate the impact of persistent no-flow AWI on short- and long-term mortality risk.
Alternatively, dedicated pharmacological treatment strategies able to tackle high thrombus burden (25) or target microcirculatory reperfusion on top of mechanical intervention (26) may prove beneficial in this newly identified high-risk subset of STEMI patients.
Our results are in keeping with Kurowski et al. (27), who found in 311 consecutive patients with successful primary PCI for STEMI, reperfusion after crossing the lesion with the guidewire to be associated to lower unadjusted mortality rates at 30 days (3.6% vs. 9.1%) and after a median of 16 months (3.6% vs. 13.9%, p = 0.03) compared with patients with no flow improvement AWI. After multivariable correction, however, wire-induced recanalization only trended to be associated to better outcomes at longest available follow-up (odds ratio: 0.30, 95% CI: 0.07 to 1.38; p = 0.12), likely reflecting a power issue and ultimately calling for larger datasets to reassess the association between response to vessel wiring and long-term outcomes.
Mortality for STEMI has substantially decreased over the last 10 years thanks to a widespread use of more efficient primary PCI networks along with landmark pharmacomechanical refinements (28). The early identification of a sizable (∼30%) proportion of patients at >5% and >9% mortality rate at 30 days and 1 year, respectively, may guide future trials to assess dedicated treatment strategies, ultimately leading to a further improvement of the already excellent prognosis generally present after primary PCI.
Although event rates in the 2 study groups were remarkably similar, we cannot rule out the possibility that a power issue may explain why patients with pre-PCI TIMI flow grade 3, when compared with patients with TIMI flow grade <3 but >0 before intervention, did not have an improved survival rate . Also, although baseline demographic differences were most likely adjusted for by the multivariate analyses, the effect of unknown confounders cannot be excluded. This is why confirmatory findings by other datasets are welcome.
Myocardial blush score, which is well known to carry prognostic implications in STEMI patients (29,30), was not systematically assessed in the STRATEGY and MULTISTRATEGY trials. Thus, the independent predictive value of TIMI flow grade 0 AWI beyond the blush score could not be evaluated. Whether and to what extent the prognostic role of TIMI flow grade 0 AWI is maintained even in patients not receiving treatment with glycoprotein IIb/IIIa inhibitors remains to be determined as, per protocol, all patients were so in our analysis.
Finally, despite multiple multivariable models having been employed to strengthen the results of our analysis, we cannot completely rule out the presence of overfitting due to a relatively low number of fatalities in the analysis.
Patients with STEMI in whom persistent no-flow AWI is detected during primary PCI are at greater risk for early and late mortality despite an apparently successful mechanical intervention. As an early and readily available prognostic marker, response to vessel wiring, may help stratifying mortality risk after primary PCI and may guide future studies to identify dedicated pharmacomechanical treatment strategies.
This study was supported by the University of Ferrara, Italy. Dr. Valgimigli has received honoraria for lectures/advisory board from Merck and Iroko, Eli Lilly Co., Daiichi Sankyo, Inc., The Medicines Company, Cordis, Abbott, and Medtronic; and has received a research grant from Eli Lilly and Iroko. All other authors report that they have no relationships to disclose.
- Abbreviations and Acronyms
- analysis of variance
- after wire insertion
- percutaneous coronary intervention
- ST-segment elevation myocardial infarction
- Thrombolysis In Myocardial Infarction
- Received March 10, 2010.
- Revision received September 10, 2010.
- Accepted September 17, 2010.
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