Journal of Thrombosis and Thrombolysis

, Volume 38, Issue 1, pp 81–86

Preprocedural TIMI flow and infarct size in STEMI undergoing primary angioplasty

Authors

    • Division of Cardiology“Maggiore della Carità” Hospital, Eastern Piedmont University
  • Guido Parodi
    • Division of CardiologyCareggi Hospital
  • Roberto Sciagrà
    • Nuclear Medicine UnityUniversity of Florence
  • Francesco Venditti
    • Division of CardiologyCareggi Hospital
  • Benedetta Bellandi
    • Division of CardiologyCareggi Hospital
  • Ruben Vergara
    • Division of CardiologyCareggi Hospital
  • Angela Migliorini
    • Division of CardiologyCareggi Hospital
  • Renato Valenti
    • Division of CardiologyCareggi Hospital
  • David Antoniucci
    • Division of CardiologyCareggi Hospital
Article

DOI: 10.1007/s11239-013-0977-x

Cite this article as:
De Luca, G., Parodi, G., Sciagrà, R. et al. J Thromb Thrombolysis (2014) 38: 81. doi:10.1007/s11239-013-0977-x

Abstract

Despite optimal epicardial recanalization, primary angioplasty for STEMI is still associated with suboptimal reperfusion in a relatively large proportion of patients. The aim the current study was to evaluate the impact of preprocedural TIMI flow on myocardial scintigraphic infarct size among STEMI undergoing primary angioplasty. Our population is represented by 793 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi. Poor preprocedural TIMI flow (TIMI 0–1) was observed in 645 patients (81.3 %). Poor preprocedural TIMI flow was associated with more hypercholesterolemia (p = 0.012), and a trend in lower prevalence of diabetes (p = 0.081). Preprocedural TIMI flow significantly affected scintigraphic and enzymatic infarct size. Similar findings were observed in the analysis restricted to patients with postprocedural TIMI 3 flow. The impact of preprocedural TIMI flow on scintigraphic infarct size was confirmed when the analysis was performed according to the percentage of patients above the median (p < 0.001) and after adjustment for baseline confounding factors (Hypercholesterolemia and diabetes) [adjusted OR (95 % CI) for pre preprocedural TIMI 3 flow = 0.59 (0.46–0.75), p < 0.001]. This study shows that among patients with STEMI undergoing primary angioplasty, poor preprocedural TIMI flow is independently associated with larger infarct size.

Keywords

STEMIPrimary angioplastyPreprocedural recanalizationInfarct sizeSPECT

Introduction

Primary angioplasty has been shown to be superior to thrombolysis, mainly due to restoration of TIMI 3 flow in the vast majority of patients [1, 2], with further improvement with the improvement of adjunctive pharmacological and mechanical devices [36]. However, epicardial recanalization does not guarantee optimal myocardial reperfusion, that is still unsatisfactory in a large proportion of patients, mainly due to no-reflow phenomenon and distal embolization [7, 8]. Time-to-treatment has been shown to be a major determinant of impaired myocardial perfusion and survival among STEMI patients undergoing primary angioplasty [914]. Early recanalization may therefore imply a shorter ischemia time and positively affect the extent of infarct size. So far few studies have investigated this issue, with most of them based on evaluation of ST-segment resolution or enzymatic infarct size [1520], while only a minority used a refined image technique for infarct size evaluation [21]. Therefore, the aim of the current study was to investigate the impact of preprocedural TIMI flow procedural results and scintigraphic infarct size.

Methods

Our population is represented by 793 STEMI patients treated by primary angioplasty undergoing evaluation of infarct size at 30 days after the intervention. All patients were admitted within 12 h from symptom onset. All patients received aspirin (500 mg intravenously) and heparin (60 IU/Kg intravenously). The decision to provide Gp IIb-IIIa inhibitors was left at the discretion of the operator. All patients were on dual oral antiplatelet therapy (aspirin and clopidogrel or ticlopidine) for at least 4 weeks after stent implantation.

Coronary angiography and mechanical revascularization

Selective coronary angiography was performed in multiple projections before mechanical reperfusion. Immediately after diagnostic angiography, percutaneous coronary intervention with stenting of the infarct-related vessel was performed using standard material. Successful primary percutaneous coronary intervention was defined as thrombolysis in myocardial infarction (TIMI) grade 3 coronary flow in the treated vessel with a residual stenosis <20 %.

Infarct size

Gated SPECT acquisition began 60 min after 99mTc-sestamibi injection (740 MBq), using a double-head camera (Picker Irix, Philips Medical System, Andover, MA) equipped with high-resolution collimators, a 180° rotation arc, 34 projections, 60 s/projection, 8 frames/heart cycle and 64 × 64 matrices [22]. The studies were reconstructed using filtered back-projection without attenuation or scatter correction and realigned along the heart axis. Perfusion defects were quantified as percentage of LV wall, with the defect threshold set at 60 % of peak uptake [23].

Statistical analysis

Statistical analysis was performed with the SPSS 15.0 statistical package. Patients were divided in three groups according to preprocedural recanalization (TIMI 01, TIMI 2 and TIMI 3). Continuous data were expressed as median [25–72th percentile] and categorical data as percentage. The ANOVA test or Mann–Whitney test were appropriately used for continuous variables, based on normality of distribution as evaluated by the Shapiro–Wilk test. The Chi square test or the Fisher’s exact test was used for categorical variables. Bonferroni correction was applied in case of multiple comparisons. Multiple logistic regression analysis was used to evaluate the impact of preprocedural TIMI flow on infarct size after adjustment for significant (p < 0.1) confounding baseline characteristics.

Results

Poor preprocedural TIMI flow (TIMI 0–1) was observed in 645 patients (81.3 %). Patients’ characteristics are reported in Table 1. Poor preprocedural TIMI flow was associated with more hypercholesterolemia (p = 0.012), and a trend in lower prevalence of diabetes (p = 0.081). No major differences were observed in other clinical, angiographic or procedural variables between the groups.
Table 1

Patients’ demographic, clionical and procedural characteristics according to preprocedural TIMI flow

Clinical Characteristics

TIMI flow 0/1 (n = 645)

TIMI flow 2 (= 87)

TIMI flow 3 (n = 61)

p value

Age (median [25th–75th])

63 [55–72]

68 [59–75]

63 [54–71]

0.26

Age >75 years (%)

19.5

26.1

16.4

0.92

Male sex (%)

78.8

78.4

83.6

0.45

Diabetes (%)

13.1

12.3

22.4

0.081

Hypercholesterolemia (%)

36.1

23.9

25.4

0.013

Smokers (%)

49.8

38.6

44.8

0.13

Arterial hypertension (%)

43.2

40.9

50.7

0.4

Previous CABG (%)

0.9

1.1

0.0

0.58

Previous PCI (%)

3.4

2.3

7.5

0.22

Shock at presentation (%)

4.1

1.1

3.0

0.23

Anterior MI (%)

37.9

60.3

37.5

0.12

Multivessel coronary disease (%)

40.3

50

43.3

0.25

Ischemia time (median [25th–75th])

200 [150–280]

195 [138–271]

185 [140–245]

0.33

Ischemia time <3 h (%)

39.6

43.5

47

0.2

Infarct-related artery (%)

   

0.15

LAD

37.9

61.4

37.3

 

LCX

14.6

10.2

17.9

 

RCA

47.2

28.4

44.8

 

SVG

0.1

0

0

 

LM

0.1

0

0

 

Stenting (%)

98.4

100

100

0.89

DES (%)

5.5

9.8

5.4

0.64

IABP (%)

3.9

3.4

3

0.92

Abciximab (%)

89.5

87.5

95.5

0.3

Postprocedural TIMI flow 3

91.7

92

97

0.18

Infarct size (above median, %)

53.3

43.7

24.6

<0.001

CKMB peak (ng/ml; median [25th–75th])

212 [134–405]

212 [66–281]

53 [11–110]

<0.001

Complete ST resolution (%)

54.3

41.4

63.6

0.77

As shown in Fig. 1, preprocedural TIMI flow significantly affected scintigraphic infarct size. Similar impact was observed on enzymatic infarct size (p < 0.0001) (Table 1). Similar findings were observed in the analysis restricted to patients with postprocedural TIMI 3 flow (Fig. 1). The impact of preprocedural TIMI flow on scintigraphic infarct size was confirmed when the analysis was performed according to the percentage of patients above the median (Fig. 2; p < 0.001) (also when restricted to patients with postprocedural TIMI 3 flow—Fig. 2) and after adjustment for baseline confounding factors (hypercholesterolemia and diabetes) [adjusted OR (95 % CI) for preprocedural TIMI 3 flow = 0.59 (0.46–0.75), p < 0.001).
https://static-content.springer.com/image/art%3A10.1007%2Fs11239-013-0977-x/MediaObjects/11239_2013_977_Fig1_HTML.gif
Fig. 1

Impact of preprocedural TIMI flow on scintigraphic infarct size in overall population (a), confirmed when restricted to patients with postprocedural TIMI 3 flow (b). a *p < 0.001 versus TIMI 3; §p = 0.22 versus TIMI 2; #p = 0.27 versus TIMI 3 b *p < 0.001 versus TIMI 3; §p = 0.14 versus TIMI 3; #p = 0.5 versus TIMI 2

https://static-content.springer.com/image/art%3A10.1007%2Fs11239-013-0977-x/MediaObjects/11239_2013_977_Fig2_HTML.gif
Fig. 2

Bar graph shows the impact of preprocedural TIMI flow on scintigraphic infarct size (as percentage of patients above the median value) in overall population (a), confirmed when restricted to patients with postprocedural TIMI 3 flow (b). a *p < 0.001 versus TIMI 3; §p = 0.28 versus TIMI 2; #p = 0.049 versus TIMI 3 b *p < 0.001 versus TIMI 3; §p = 0.34 versus TIMI 2; #p = 0.054 versus TIMI 3

Discussion

The main finding of the present study is that among STEMI patients undergoing primary angioplasty, poor preprocedural TIMI flow was independently associated with larger scintigraphic infarct size.

The feasibility and superiority of long-distance transportation for primary angioplasty in comparison with on-site thrombolysis have been confirmed in several trials [2]. However, the potential time delay for transportation remains a major drawback to primary angioplasty [24]. Time to treatment has recently been shown to be a predictor of mortality not only for thrombolysis but also for primary angioplasty [914]. Large interest has been focused on preprocedural recanalization, that may imply shorter ischemia time and therefore may favourably impact on clinical outcome. Stone et al. [15] found preprocedural but not post-procedural TIMI 3 flow to be independent predictor of mortality. The role of preprocedural TIMI flow on outcome has been confirmed by Brodie et al. [16] who found, in a cohort of 1490 patients treated by primary angioplasty, preprocedural TIMI 2–3 to be associated with the amount of cardiac enzyme release, ejection fraction, and mortality. Similar findings have been observed by De Luca et al. [17, 18] and Dudek et al. [19] and Maioli et al. [20].

Few reports have investigated the relationship between preprocedural recanalization and infarct size as evaluated by refined imaging techniques. Ndrepepa et al. [21], showed that preprocedural TIMI flow significantly affected the extent of infarct size and myocardial salvage among 118 STEMI patients undergoing primary angioplasty.

Similar findings have been observed in our study, where preprocedural TIMI flow independently affected infarct size. The impact of preprocedural TIMI flow on infarct size was confirmed also in the analysis restricted to patients with post-procedural TIMI 3 flow and after correction for baseline confounding factors.

Several factors may explain the preprocedural TIMI flow-dependent mechanism of impaired myocardial perfusion despite optimal epicardial flow. Experimental studies have shown that long ischemic time may induce morphological alterations (swelling of endothelial and cardiac cells, with occlusion or compression of microcirculation) in the cardiac capillaries and arterioles [25]. Furthermore, recent studies have focused on the role of micro-embolization of atherosclerotic debris, blood clots, and platelet plugs in the microcirculation [26]. A delay in reperfusion may be associated with an older, organized, intracoronary thrombus, in comparison with an early reperfusion [27]. This may result in a higher incidence of distal micro-embolization and poor myocardial perfusion, despite optimal epicardial flow [28]. The importance of early reperfusion is clearly supported by the larger extension of myocardial necrosis observed with poor preprocedural TIMI flow. Previous trials have failed to show benefits from early recanalization obtained by full-dose lysis or combo-therapy at short-term follow-up. However, recent sub-analyses from the FINESSE trial [29] showed benefits in 1-year survival from combo-therapy in high-risk patients when presenting within the first 4 h from symptoms onset. Benefits in primary outcome were observed in such a patients also from early abciximab administration. Several additional reports have investigated the benefits from early Gp IIb-IIIa inhibitors in primary angioplasty. The EGYPT cooperation showed significant benefits in mortality form early abciximab administration [30, 31]. Similar findings have been observed in the EUROTRANSFER Registry [32] and in the REAL registry [33]. All these data together encourage pharmacological facilitation especially within the first hours from symptoms onset, the so called “golden hours”, when early pharmacological therapy is more effective in the recanalization of a fresh thrombus, that is especially important in high-risk patients. These recent evidences contributed to upgrade european STEMI guidelines recommendations on upstrem Gp IIb-IIIa inhibitors from class III from class IIb [34]. Recently, the STREAM trial aimed at comparing two reperfusion strategies (pharmacological vs mechanical) for STEMI patients presenting within the first 3 h from symptoms onset and not able to undergo PCI within 1 h from medical contact [35]. This study showed a trend in benefits, especially after study amendment on elderly patients. However, while examining a pharmaco-invasive approach, the study did not truly evaluate facilitated angioplasty, since most of the patients in the lythic group underwent angiography only between 6 and 24 h after lysis administration.

Limitations

We assessed the infarct size at 1 month after index infarction instead of at hospital discharge or at 2 weeks [21], as in the majority of previously published studies. On the other hand, this circumstance should be more effective in preventing interference of myocardial stunning with the extent of perfusion defects [36]. Moreover, the execution of a coronary angiographic control before gated SPECT allowed the exclusion of infarct-related vessel restenosis. The availability of myocardial salvage would have certainly improved our results. Furthermore, because we studied a patient population submitted to a very aggressive revascularisation protocol, including early direct percutaneous coronary intervention, caution should be exercised when extending our data to infarct patients submitted to other types of reperfusion therapy. Finally, the relatively small population (especially for preprocedural TIMI 2 and 3 patients), did not provide enough statistical power and therefore limited our ability to fully explore a statistical difference between each group by the use of multiple comparisons.

Conclusions

This study shows that among patients with STEMI undergoing primary angioplasty poor preprocedural TIMI flow is independently associated with larger infarct size.

Copyright information

© Springer Science+Business Media New York 2013