Cardiovasc Interv and Ther DOI 10.1007/s12928-014-0295-z

ORIGINAL ARTICLE

Impact of transient or persistent slow flow and adjunctive distal protection on mortality in ST-segment elevation myocardial infarction Toshiharu Fujii • Naoki Masuda • Masataka Nakano • Gaku Nakazawa • Norihiko Shinozaki • Takashi Matsukage Nobuhiko Ogata • Fuminobu Yoshimachi • Yuji Ikari



Received: 24 May 2014 / Accepted: 19 August 2014 Ó Japanese Association of Cardiovascular Intervention and Therapeutics 2014

Abstract Routine use of distal protection for ST-segment elevation myocardial infarction (STEMI) is not recommended. The purpose of this study was to analyze the impact of slow flow on mortality after STEMI, and the efficacy of adjunctive distal protection following primary thrombus aspiration. We retrospectively analyzed 414 STEMI patients who underwent primary PCI. Distal protection was used following primary thrombus aspiration only when the operator judged the patient to be at high risk of slow flow. Patients were divided into 3 groups: those receiving no thrombus aspiration (A- Group), thrombus aspiration without distal protection (A?/D- Group) or a combination of aspiration with distal protection (A?/D? Group). Slow flow/no reflow was characterized as transient or persistent. The A-, A?/D-, and A?/D? Groups consisted of 28.5 % (n = 118), 44.4 % (n = 184), and 27.1 % (n = 112) of patients, respectively. All-cause mortality at 180 days was 6.8 % without slow flow, 14.1 % with transient and 44.4 % with persistent slow flow (P \ 0.0001), but was similar whether or not distal protection was used among these groups complicated without slow flow (A-, 8.7 %; A?/D-, 6.3 %; A?/D?, 4.3 %; P = 0.5854). However, in cases complicated with transient or persistent slow flow, distal protection reduced all-cause mortality to 38.5 % (A-), 23.3 % (A?/D-), and 10.8 % (A?/D?) at 180 days (P = 0.0114). Our data confirm that routine distal protection is not to be recommended. However, it is suggested that it could reduce mortality of

T. Fujii  N. Masuda  M. Nakano  G. Nakazawa  N. Shinozaki  T. Matsukage  N. Ogata  F. Yoshimachi  Y. Ikari (&) Department of Cardiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan e-mail: [email protected]

patients with slow flow. Predicting slow flow accurately before PCI, however, remains a challenge. Keywords ST-segment elevation myocardial infarction  Percutaneous coronary intervention  Distal protection device  Thrombus aspiration  Slow flow

Introduction Primary percutaneous coronary intervention (PCI) is the optimal reperfusion modality for acute ST-segment elevation myocardial infarction (STEMI) and has contributed to improved survival. PCI frequently restores normal coronary epicardial flow, but myocardial perfusion is often suboptimal. Numerous mechanisms underlie the etiology of dysfunctional coronary microcirculation. Distal embolism of thrombus and plaque components caused by PCI is one common mechanism, which results in microvascular dysfunction with low myocardial blush grade or slow flow/ no reflow phenomena [1]. This contributes to impaired myocardial perfusion and adverse clinical outcomes [2–10]. Primary thrombus aspiration is effective in achieving better blush grade and improving survival. Some studies suggested that distal protection is effective in prevention of distal emboli or reduction of slow flow [11–27]. However, the routine use of distal protection devices is not generally recommended because this approach failed to improve clinical outcome [11, 13, 28]. During primary PCI, we have sometimes observed slow flow following the final stent implantation despite good epicardial and myocardial reperfusion using thrombus aspiration before stenting. If distal protection is used as a secondary technique after achievement of coronary

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T. Fujii et al.

reperfusion using thrombus aspiration, it could prevent deterioration of microcirculation by stenting, without delaying reperfusion time. To date, the effect of adjunctive distal protection has not been reported. The purpose of the present study was to analyze the impact of transient or persistent slow flow on mortality of STEMI, and the ability of adjunctive distal protection device use following primary thrombus aspiration to decrease mortality worsened by slow flow.

Methods To study the additional benefit of using a distal protection device for improving clinical outcome in STEMI, supplemental to thrombus aspiration and considering the impact of slow flow thereon, we retrospectively studied the medical records of 414 consecutive STEMI patients who underwent primary PCI within 24 h of symptom onset from December 2005 to March 2011 at Tokai University School of Medicine. Patients with culprit lesions due to stent thrombosis and coronary bypass grafts were excluded. Thrombus aspiration was the initial procedure for revascularization. Thereafter, when considered necessary, a filter-based distal protection device (FiltrapTM, Nipro, Japan) was used to protect patients from distal emboli during stent implantation [29]. The use of these adjunctive devices (i.e., distal protection device and/or thrombus aspiration device) was at the discretion of the operator. We assessed slow flow or no reflow in the final coronary angiography. The patients were divided into the following 3 groups according to their receipt of thrombus aspiration and use of the distal protection device: (1) no aspiration device (A- Group), (2) aspiration but no distal protection device (A?/D- Group), and (3) use of both a distal protection device and aspiration device (A?/D? Group) (Fig. 1). Patients were followed for up to 180 days after PCI. Clinical outcomes at 180 days from the onset of STEMI Fig. 1 Flowchart for assignment to one of the 3 Groups

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were assessed regarding the impact of slow flow or adjunctive devices. The patients who we could not track 180-day mortality after STEMI onset were excluded from present study. Definitions STEMI was defined as acute onset of symptoms with concurrent electrocardiographic findings such as persistent ST-segment elevation [1 mm in 2 contiguous leads, new or presumed new left bundle branch block, and coronary occlusion confirmed by emergency coronary angiography [30]. The slow flow and no reflow phenomena were treated as the event of concern in this study. These were determined based on the definition of TIMI flow grade [31]. Among slow flow or no reflow events during PCI, patients with TIMI 3 flow in the final angiogram were classified as ‘‘transient slow flow’’. On the other hand, patients with persistent slow flow-up until the final angiogram, were designated ‘‘persistent slow flow’’. The filter devicedependent slow flow was defined as the slow flow that developed after distal protection setting and improved by the removal of it. PCI procedure and devices Interventional strategies including the application of adjunctive devices or other devices for the achievement of procedural success were at the discretion of an experienced operator. FiltrapTM was exclusively used as the distal protection device. This is a 0.016 wire system with selfexpandable basket composed of 8 pieces of nickel–titanium rod and a polyurethane membrane. All patients received dual antiplatelet therapy before PCI. Bolus unfractionated heparin (100 U/kg body weight) was administered before PCI. Heparin, checked every hour, was added as necessary to maintain activated clotting time [250 s.

Adjunctive filter device after thrombectomy

Statistical analysis Numerical values with normal distribution are shown as mean ± standard deviation. Analysis of variance (ANOVA) was performed to compare the numerical parameters among the 3 groups. Pearson’s Chi square test was applied to determine the difference between categorical variables. Survival analysis is displayed according to the Kaplan–Meier method. Comparisons of survival curves were performed by the log-rank method. Backward stepwise multivariable logistic regression models were used to examine the independent predictors. For selection of variables, a backward stepwise selection procedure was adopted in stepwise regression analysis to identify factors associated with 180-day morality or development of slow flow. The variable entered in the stepwise model was the variable that had the smallest P value [0.25. The analysis was stopped when no more variables could be justifiably entered from the stepwise model. To examine the development of slow flow, gender, age, hypertension, dyslipidemia, diabetes mellitus treated with insulin, estimated glomerular filtration rate, Killip classification, shock on arrival, and experience of cardiopulmonary arrest were tested. And to examine the independent predictors of the 180-day mortality, gender, age, diabetes mellitus treated with insulin, estimated glomerular filtration rate, blush score, final TIMI score, and usage of distal protection device after thrombus aspiration were tested. The goodness of fit for multivariable analysis was tested by the Hosmer– Lemeshow test. The results of multivariate analysis were summarized by odds ratios (OR) and 95 % confidence intervals (CI). P \ 0.05 was considered statistically significant. All statistical calculations were performed using JMP version 9 (SAS Institute, Inc., Cary, NC, USA).

Results Patients’ baseline characteristics are shown in Table 1. Mean age was 66.1 ± 13.0 years and 79.0 % of the patients were male. Thrombus aspiration was performed as the initial procedure in 71.5 % of the total of 414 STEMI patients (Fig. 1). Thereafter, when there were concerns about distal embolism based on the coronary angiography after thrombus aspiration, a filter-based distal protection device was used. This was the case in 37.8 % of patients (A?/D? Group; 112/296 patients). However, when operators did not anticipate any problems with embolism according to the baseline coronary angiography, thrombus aspiration was not performed (A- Group; 28.5 % of patients). Table 2 shows patients’ clinical status on arrival and parameters measured as in-patients. The A- Group had the

Table 1 Baseline characteristics Age (years)

66.1 ± 13.0

Male (n)

327 (79.0 %)

Height (cm)

162.5 ± 8.6

Weight (kg)

63.9 ± 13.7

Current smoking (n)

268 (64.7 %)

Diabetes mellitus (n)

164 (39.6 %)

Dyslipidemia (n)

288 (69.6 %)

Hypertension (n)

339 (81.9 %)

Family history (n)

63 (15.2 %)

Old MI (n)

44 (10.6 %)

Prior PCI (n)

31 (7.5 %)

Prior CABG (n)

1 (0.2 %)

Prior stroke (n)

55 (13.3 %)

Hemodialysis (n)

10 (2.4 %)

DM Non-DM

5 (1.2 %) 5 (1.2 %)

Hemoglobin (mg/dl)

14.1 ± 2.4

Total cholesterol (mg/dl)

191.4 ± 45.6

Triglyceride (mg/dl)

119.3 ± 108.0

Serum creatinine (mg/dl)

1.2 ± 1.4

Estimated GFR (ml/min/1.73 m2)

64.1 ± 24.3

BNP (pg/dl)

250.5 ± 506.4

MI myocardial infarction, PCI percutaneous coronary intervention, CABG coronary artery bypass grafting, DM diabetes mellitus, GFR glomerular filtration rate, BNP brain natriuretic peptide

lowest use of intravascular ultrasound (IVUS), the longest hospital stay and the highest use of supportive devices (intra-aortic balloon pump or percutaneous cardiopulmonary support) despite the lowest peak creatine phosphokinase among the 3 groups. The average diameter of deployed stents was smaller in the A- Group than in the other two groups. Figure 2 shows that the rate of occurrence of transient slow flow/no reflow was proportional to the level of protection (A- Group, 11.9 %; A?/D- Group, 32.6 %; A?/ D? Group, 48.2 %). However, persistent slow flow/no reflow was similarly frequent in the 3 groups (A- Group, 10.2 %; A?/D- Group, 7.1 %; A?/D? Group, 9.8 %). Furthermore, slow flow/no reflow was observed in 22 % of the A- Group in which operators had failed to anticipate this complication. The filter device-dependent slow flow was included 11.6 % (13/112 patients) in A?/D? Group. In the study to extract the independent predictors of the development of slow flow, dyslipidemia and experience of cardiopulmonary arrest were extracted as the variables of a final model, and these were confirmed as the independent predictors of slow flow (OR 1.59; 95 % CI 1.02–2.42; P = 0.0414 and OR 2.87; 95 % CI 1.62–5.15; P = 0.0003, respectively).

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T. Fujii et al. Table 2 Clinical status on arrival and in-hospital parameters Total (n = 414)

Aspiration(n = 118)

Aspiration?

P value

Distal protection(n = 184)

Distal protection? (n = 112)

Systolic BP (mmHg)

127.6 ± 40.3

126.5 ± 50.0

128.6 ± 34.5

127.1 ± 37.4

0.8940

Shock on arrival (n)

85 (20.5 %)

31 (26.2 %)

34 (18.5 %)

20 (17.9 %)

0.1995

Killip I (n) Cardiopulmonary arrest (n)a

191 (46.1 %) 58 (14.0 %)

48 (40.7 %) 18 (15.3 %)

87 (47.3 %) 24 (13.0 %)

56 (50.0 %) 16 (14.3 %)

0.3354 0.8435

Onset to first device activation (min)

304.3 ± 212.6

337.1 ± 230.0

288.0 ± 200.2

296.7 ± 211.4

0.1328

128 (30.9 %)/36 (8.7 %)

14 (11.9 %)/12 (10.2 %)

60 (32.6 %)/13 (7.1 %)

54 (48.2 %)/11 (9.8 %)

TIMI 3 in final angiogram (n)

373 (90.1 %)

103 (87.3 %)

170 (92.4 %)

100 (89.3 %)

Success of PCI (n)

371 (89.6 %)

103 (87.3 %)

168 (91.3 %)

100 (90.2 %)

0.5719

Peak CK (IU/l) Ejection fraction (%)

4048.6 ± 4874.7 50.1 ± 13.3

3053.4 ± 3915.0 49.9 ± 15.7

4629.3 ± 5980.2 49.8 ± 12.6

4134.4 ± 3407.9 50.9 ± 11.5

0.0229 0.7693

Slow flow/no reflow (n) Transient/persistent

\0.001 0.3229

CCU stay (days)

5.9 ± 9.1

7.0 ± 11.5

5.9 ± 9.6

4.7 ± 3.6

0.1485

Length of hospitalization (days)

16.7 ± 19.6

20.1 ± 28.4

15.4 ± 14.0

15.2 ± 15.6

0.0789

Complications related to PCI (n)

68 (16.4 %)

20 (16.9 %)

31 (16.8 %)

17 (15.2 %)

0.9279

Tamponade

3 (0.7 %)

0

2 (1.1 %)

1 (0.9 %)

0.6236

VT/VF/asystole

55 (13.3 %)

17 (14.4 %)

26 (14.1 %)

12 (10.7 %)

0.6629

Hematoma/bleeding Transfusion

4 (9.7 %) 6 (1.4 %)

2 (1.7 %) 1 (0.8 %)

0 3 (1.6 %)

2 (1.8 %) 2 (1.8 %)

0.1289 0.8828

Procedural time (min)

109.3 ± 49.9

110.3 ± 58.0

106.7 ± 49.4

112.3 ± 40.9

0.6252

Contrast volume (ml)

230.7 ± 85.0

226.6 ± 94.7

227.3 ± 79.5

240.6 ± 82.9

0.3648

IVUS (n)

354 (85.5 %)

86 (72.9 %)

161 (87.5 %)

107 (95.5 %)

Supportive device (n)

103 (24.9 %)

42 (35.6 %)

44 (23.9 %)

17 (15.2 %)

IABP alone

82 (19.8 %)

32 (27.1 %)

35 (19.0 %)

15 (13.4 %)

PCPS alone

1 (0.2 %)

0

0

1 (0.9 %)

IABP ? PCPS

20 (4.8 %)

10 (8.5 %)

9 (4.9 %)

1 (0.9 %)

RCA

155 (37.4 %)

35 (29.7 %)

70 (38.0 %)

50 (44.6 %)

LAD

186 (44.9 %)

53 (44.9 %)

80 (43.5 %)

53 (47.3 %)

LCX

42 (10.1 %)

15 (12.7 %)

18 (9.8 %)

8 (7.1 %)

LMT

21 (5.1 %)

11 (9.3 %)

9 (4.9 %)

1 (0.9 %)

Others

11 (26.6 %)

4 (3.4 %)

7 (3.8 %)

0

\0.001 0.0022

Culprit lesion (n)

Deployed stent Number (n)

0.0235

1.3 ± 0.8

1.5 ± 0.9

1.3 ± 0.5

1.4 ± 0.8

Diameter (mm)

3.2 ± 0.4

3.1 ± 0.4

3.2 ± 0.4

3.4 ± 0.4

0.0115

Total length (mm)

29.2 ± 24.7

33.0 ± 3.0

27.1 ± 23.8

28.8 ± 19.5

0.1442

115/131/168

33/38/47

49/59/76

33/34/45

0.7771

\0.001

Blush grade 0 or 1/2/3

BP blood pressure, TIMI thrombolysis in myocardial infarction grade, PCI percutaneous coronary intervention, CK creatine phosphokinase, CCU coronary care unit, EF ejection fraction, VT ventricular tachycardia, VF ventricular fibrillation, IVUS intravascular ultrasound, IABP intra-aortic balloon pump, PCPS percutaneous cardiopulmonary support, RCA right coronary artery, LAD left anterior descending artery, LCX left circumflex coronary artery, LMT left main coronary trunk a

Patients who experienced cardiopulmonary arrest from onset to the end of PCI

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Adjunctive filter device after thrombectomy

Fig. 2 Proportion of patients with slow flow in the 3 Groups. The proportion of patients with persistent or transient slow flow in each group was as follows: 10.2 % (12/118) and 11.9 % (14/118), 7.1 % (13/184) and 32.6 % (60/184), and 9.8 % (11/112) and 48.2 % (54/

112), respectively. Slow flow was more frequent in the group with the use of adjunctive devices. However, the efficacy of improvement of slow flow was superior in the group with distal protection

Table 3 shows the background and clinical outcome after stratifying patients into 3 groups according to their flow status. The persistent slow flow group included more patients in shock or with cardiopulmonary arrest, left main disease and lower ejection fraction. During PCI, the persistent slow flow group frequently suffered ventricular tachycardia/ventricular fibrillation/asystole and required frequent use of supportive devices. Table 4 shows the clinical outcomes 180 days after PCI. The mortality rate was 44.4 % in the persistent slow flow group. Kaplan–Meier survival analysis revealed significant differences between groups. Thus, mortality was 6.8 % when there was no slow flow: 14.1 % in the transient slow flow group, but 44 % in the persistent slow flow group (P \ 0.001; Fig. 3a). The 180-day mortalities among 3 groups in all population were equivalent (A-, 15.3 % vs. A?/D-, 13.0 % vs. A?/D?, 8.0 %, P = 0.2307). Patients were divided into 2 groups, without or with slow flow (Fig. 3b, c). In the former, there were no differences in 180-day mortality rates, which were 8.7 % (A- Group), 6.3 % (A?/D- Group), and 4.3 % (A?/D? Group) (P = 0.5854) (Fig. 3b). However, in patients with either transient or persistent slow flow, the use of the distal protection device after thrombus aspiration (A?/D? Group) decreased mortality at 180 days in addition to the benefit conveyed by thrombus aspiration. Thus, mortality was 38.5 % (A- Group), 23.3 % (A?/D- Group), and 10.8 % (A?/D? Group) (P = 0.0114; Fig. 3c). Backward stepwise model reduction to examine the independent predictors of 180-day death resulted in a final model with the following factors: age C75, DM treated with insulin, estimated GFR, blush score C2, final TIMI 3, and distal protection after thrombus aspiration. Among them, age C75, blush score, C2, final TIMI 3, and distal

protection after thrombus aspiration were extracted as the independent predictors of 180-day death (Table 5).

Discussion This study showed that the use of filter-based distal protection following primary thrombus aspiration did not decrease 180-day mortality in STEMI patients without slow flow. However, it did have a beneficial effect in STEMI patients with transient or persistent slow flow. This beneficial effect of distal protection following thrombus aspiration may have generated synergetic effects only in cases of slow flow. Primary PCI is a standard treatment for patients with STEMI. However, mechanical stress exerted on the ruptured plaque by ballooning or stenting may lead to release of thrombi and cause capillary occlusion atheroma emboli, edema, or endothelial damage [32, 33]. A poor myocardial blush score predicts a higher rate of long-term mortality in patients with STEMI [5]. Furthermore, angiographic slow flow or no reflow is a predictor of high mortality, even if only transient [7, 9, 10, 34]. Maintaining coronary microcirculation is therefore an important factor for achieving prompt reperfusion and reducing mortality. Studies including EMERALD, DEDICATION, and PREMIAR failed to demonstrate any improvement of adverse clinical outcomes using a distal protection device [13–15, 17, 20–22, 24, 35, 36]. Furthermore, some reported that it even increased mortality. One of the main reasons for these negative results could be that applying distal protection prolongs the time to reperfusion. For example, the EMERALD trial cited an additional 21 min of delay in the distal protection group as the number one reason why

123

T. Fujii et al. Table 3 Comparison of baseline characteristics and clinical status on arrival

Slow flow(n = 250)

Transient slow flow (n = 128)

Persistent slow flow (n = 36)

P value

Age (years)

66.0 ± 12.2

65.7 ± 13.0

68.5 ± 17.5

0.5021

Male (n)

194 (77.6 %)

104 (81.3 %)

29 (80.6 %)

0.6914

Height (cm)

162.3 ± 8.4

162.5 ± 9.2

164.1 ± 8.4

0.5093

Weight (kg)

63.0 ± 0.9

64.5 ± 1.2

68.4 ± 2.3

0.0775

Current smoking (n)

163 (65.2 %)

82 (64.0 %)

23 (63.9 %)

0.8134

DM (n)

95 (38.0 %)

47 (36.7 %)

12 (33.3 %)

0.4557

Dyslipidemia (n)

184 (73.4 %)

80 (62.5 %)

24 (66.7 %)

0.0787

Hypertension (n)

208 (83.2 %)

100 (78.1 %)

31 (86.1 %)

0.0049

Hemodialysis (n)

7 (2.8 %)

3 (2.3 %)

0

0.8196

Serum creatinine (mg/dl)

1.2 ± 1.5

1.2 ± 1.3

1.1 ± 0.5

0.9378

Estimated GFR (ml/min/ 1.73 m2)

64.6 ± 24.2

65.5 ± 24.8

55.4 ± 22.4

0.0791

BNP (pg/dl)

254.4 ± 446.3

236.6 ± 601.5

272.6 ± 566.7

Systolic BP (mmHg)

134.2 ± 39.3

120.4 ± 38.2

107.6 ± 44.6

0.9221 \0.001

Shock on arrival (n)

41 (16.4 %)

29 (22.7 %)

15 (41.7 %)

0.0270

Killip I (n)

124 (49.6 %)

59 (46.1 %)

8 (22.2 %)

0.0029

Cardiopulmonary arrest (n)a

22 (8.8 %)

24 (18.8 %)

12 (33.3 %)

Onset to first device activation (min)

303.4 ± 189.1

302.3 ± 258.8

318.0 ± 189.3

Success of PCI (n)

244 (97.6 %)

127 (99.2 %)

0

\0.001

Peak CK (IU/l)

3408.0 ± 3799.1

4428.9 ± 5799.2

7233.5 ± 6528.6

\0.001 \0.001

\0.001 0.9207

Ejection fraction (%)

51.1 ± 13.0

50.7 ± 13.1

41.2 ± 13.0

CCU stay (days)

5.3 ± 6.0

6.2 ± 11.3

9.5 ± 15.4

0.0273

Length of hospitalization (days)

16.5 ± 16.4

17.0 ± 24.2

17.2 ± 22.6

0.9621

Complications related to PCI (n)

DM diabetes mellitus, GFR glomerular filtration rate, BNP brain natriuretic peptide, BP blood pressure, PCI percutaneous coronary intervention, CK creatine phosphokinase, CCU coronary care unit, EF ejection fraction, VT ventricular tachycardia, VF ventricular fibrillation, A- AGroup, A? D- A?/D- Group, A? D? A?/D? Group, IVUS intravascular ultrasound, IABP intra-aortic balloon pump, PCPS percutaneous cardiopulmonary support, RCA right coronary artery, LAD left anterior descending artery, LCX left circumflex coronary artery, LMT left main coronary trunk a

Patients who experienced cardiopulmonary arrest from onset to the end of PCI

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Tamponade

1 (0.4 %)

2 (1.6 %)

0

VT/VF/asystole

20 (8.0 %)

23 (18.0 %)

12 (33.3 %)

Hematoma/bleeding

2 (0.8 %)

2 (1.6 %)

0

Transfusion

1 (0.4 %)

4 (3.1 %)

1 (2.7 %)

Procedural time (min)

101.4 ± 47.4

115.7 ± 50.9

140.9 ± 48.9

Contrast volume (ml)

223.3 ± 84.8

238.4 ± 83.3

255.8 ± 87.5

\0.001

\0.001 0.0510

Adjunctive devices (n) A-/A? D-/A? D? IVUS (n)

92/111/47

14/60/54

12/13/11

215 (86.0 %)

112 (87.5 %)

27 (75.0 %)

\0.001

Supportive device (n) IABP alone

47 (18.8 %)

0

8 (22.2 %)

PCPS alone

21 (8.4 %)

1 (0.8 %)

5 (13.9 %)

IABP ? PCPS

14 (5.6 %)

0

7 (19.4 %)

\0.001

Culprit lesion (n) RCA

94 (37.6 %)

52 (40.6 %)

9 (25.0 %)

LAD

114 (45.6 %)

59 (46.1 %)

13 (36.1 %)

LCX

25 (10.0 %)

12 (9.4 %)

4 (11.1 %)

LMT

9 (3.6 %)

4 (3.1 %)

8 (22.2 %)

Others

8 (3.2 %)

1 (0.8 %)

2 (5.6 %)

0.0047

Deployed stent Number (n)

1.4 ± 0.7

1.4 ± 0.8

1.6 ± 0.9

0.3254

Diameter (mm)

3.2 ± 0.4

3.2 ± 0.4

3.2 ± 0.5

0.4254

Total length (mm)

29.3 ± 27.7

28.5 ± 19.3

31.0 ± 19.5

0.8707

Adjunctive filter device after thrombectomy Table 4 Clinical outcomes at 180 days Mortality (n)

Slow flow(n = 250)

Transient slow flow (n = 128)

Persistent slow flow (n = 36)

P value \0.001

51 (12.4 %)

17 (6.8 %)

18 (14.1 %)

16 (44.4 %)

Cardiogenic

40 (9.7 %)

8 (3.2 %)

17 (13.3 %)

15 (41.7 %)

Non-cardiogenic

10 (2.4 %)

9 (3.6 %)

0

1 (2.8 %)

Unknown CABG (n) Stent thrombosis (n)

0

1 (0.8 %)

0

14 (3.4 %)

1 (0.2 %)

12 (4.8 %)

0

2 (5.6 %)

0.0380

5 (1.2 %)

3 (1.2 %)

1 (0.8 %)

1 (2.8 %)

0.4587

Acute

2 (0.5 %)

1 (0.4 %)

1 (0.8 %)

0

Sub-acute

2 (0.5 %)

1 (0.4 %)

0

1 (2.8 %)

Late

1 (0.2 %)

1 (0.4 %)

0

0

11 (2.7 %)

8 (3.2 %)

3 (2.3 %)

0

Cardiogenic CI Non-cardiogenic CI

6 (1.4 %) 3 (0.7 %)

5 (2.0 %) 1 (0.4 %)

1 (0.8 %) 2 (1.6 %)

0 0

Hemorrhage

2 (0.5 %)

2 (0.8 %)

0

0

Stroke (n)

CABG coronary artery bypass grafting, CI cerebral infarction

Total (n = 414)

the study failed to show an improvement in clinical outcomes [11, 13, 28], and suggested that the time delay associated with distal protection procedures might offset any gain otherwise achieved. Because of these unexpected results the authors did not recommend the routine use of distal protection during PCI of native coronary lesions [37]. In contrast, thrombus aspiration as a first approach is well established as a method to improve clinical outcomes in STEMI. Thrombus aspiration clearly reduces thrombus burden without increasing the time to reperfusion because of the simple structure of the device and simple procedure [16, 20, 25–27, 38]. Many operators see a dramatic improvement during primary thrombus aspiration just after the wire passes the lesion, resulting in prompt recanalization. Unfortunately, however, there are significant numbers of cases experiencing slow flow despite appropriate thrombus aspiration. Because deploying a distal protection device after achieving reperfusion first by thrombus aspiration does not delay reperfusion time, it may be considered as a rational procedure to employ. However, there have been no reports about the efficacy of distal protection following thrombus aspiration. The present retrospective study showed that adjunctive application of distal protection did not worsen mortality overall, and in fact reduced mortality in STEMI patients experiencing slow flow. Slow flow/no reflow rates were linearly proportional to the level of protection but not closely so in this study, illustrating current limitations of angiographic prediction of slow flow. If there was an accurate method to predict slow flow, the use of distal protection devices following primary thrombus aspiration could be recommended for such cases. If it is possible to differentiate the cases in which adjunctive devices have the benefit, the randomization trial can be conducted to discuss the usefulness of adjunctive devices. Though it is reported

0.5839

the usefulness of imaging modalities such as IVUS or optical coherence tomography to predict the incidence of slow flow, the future challenge is to accumulate clearer evidences [39, 40]. A filter-based distal protection device has a possibility to develop the filter device-dependent slow flow. Present study showed it in 11.6 % of A?/D? Group, but no death was observed. Except patients with the filter devicedependent slow flow, the frequency of transient slow flow was equivalent between A?/D- and A?/D? Group (A?/ D-, 32.6 % vs. A?/D?, 36.6 %, P = 0.4816). Therefore a filter-based distal protection device increases a semblance of transient slow flow, but it does not contribute to the mortality. Present study shows the possibility to the efficacy of the distal protection for the improvement of the mortality in patients with slow flow. There are major limitations to the present study, first and foremost because it is a retrospective. We cannot exclude patient selection bias; however, present study showed the possibility to improve their mortality that is worsened by slow flow. In particular, it may be noted that inconsistency in the use of IVUS may play a part in prediction of slow flow because this may have influenced the decision to use the distal protection device, as well as affecting the choice of stent diameter size and length. Moreover, A- Group had more cases with left main trunk lesion demonstrating high mortality, and might have a slight impact on the comparison of the mortality among groups, while there was no significant difference among the 3 groups. The mortalities among 3 groups in all population had no significant difference; however, A- Group appears to have a high mortality despite the low frequency of slow flow. The selection bias, especially A- Group included more patients with left main trunk lesion compared with other groups, might contribute to this result. Since the cases with severe

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T. Fujii et al. Fig. 3 All-cause 180-day mortality. a Upper panel a comparison of all-cause 180-day mortality in 414 patients stratified into 3 groups. Patients with transient slow flow tended toward higher mortality, and persistent slow flow significantly increased mortality [6.8 % (without slow flow), 14.1 % (Transient slow flow), and 44.4 % (Persistent slow flow), P \ 0.001]. b Middle panel a comparison of all-cause 180-day mortality among 250 patients without either transient or persistent slow flow: 8.7 % (A- Group), 6.3 % (A?/DGroup), and 4.3 % (A?/D? Group) (P = 0.5854). c Lower panel a comparison of all-cause 180-day mortality among 164 patients with slow flow: 38.5 % (A- Group), 23.3 % (A?/DGroup), and 10.8 % (A?/D? Group) (P = 0.0114)

myocardial damage have a tendency to incidence slow flow, it might contribute to worsened mortality in slow flow. Present study has high proportion of cases with cardiopulmonary arrest that have high incidence rate of slow flow. Studying whether adjunctive devices have the benefit for these severe cases is one of future challenge. This study also included slow flow cases with transient slow flow. The filter device might itself have influenced slow flow in some cases. Because it is very difficult to differentiate the filter device-dependent slow flow from genuine slow flow, we need to be careful when we interpret the results of this study. Since the impact of the filter device-dependent slow flow on the mortality is regarded as considerably smaller, the improvement effect of adjunctive devices on the mortality might be underestimated. In slow flow cases, the operators were able to utilize some additional options to improve coronary flow, such as nitrates, as well as

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Table 5 The predictors of 180-day death Variables

OR (95 % CI)

P value

Age C75

2.89 (1.43–5.89)

0.0031

Insulin DM

2.26 (0.63–7.43)

0.2027

eGFR B40

2.01 (0.88–4.43)

0.0949

Blush score C2

0.12 (0.05–0.23)

\0.0001

Final TIMI 3

0.18 (0.08–0.43)

\0.0001

Distal protection after thrombus aspiration

0.41 (0.16–0.95)

0.0369

DM diabetes mellitus

adjunctive devices. The myocardial blush score was not evaluated. These differences might have contributed to the outcomes of this study. Furthermore, because the time interval after onset of symptoms for inclusion in this study was relatively long (up to 24 h from onset of the

Adjunctive filter device after thrombectomy

symptoms), this design might have contributed to these results. The characteristics of thrombi and ruptured vulnerable plaques change very quickly, and the frequency of slow flow or distal emboli in STEMI changes with time. In this regard, the VAMPIRE trial showed that slow flow was more frequent in STEMI patients presenting later than 6 h after the onset of symptoms than those presenting earlier, and using an aspiration device was more effective in this population [25]. In other words, the time interval from onset to intervention might influence both slow flow severity and the efficacy of adjunctive devices. In conclusion, distal protection following primary thrombus aspiration may reduce mortality of those STEMI patients with slow flow, because the combined application of distal protection offsets the disadvantage in time delay until recanalization. To benefit from the use of adjunctive distal protection devices, it is necessary to select patients with high risk of slow flow. Therefore, the future issue to be addressed is accurate prediction of those patients at high risk of slow flow.

References 1. Gibson CM, Cannon CP, Daley WL, Dodge JT Jr, Alexander B Jr, Marble SJ, et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation. 1996;93:879–88. 2. Simes RJ, Topol EJ, Holmes DR Jr, White HD, Rutsch WR, Vahanian A, et al. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. Gusto-i investigators. Circulation. 1995;91:1923–8. 3. Morishima I, Sone T, Okumura K, Tsuboi H, Kondo J, Mukawa H, et al. Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol. 2000;36:1202–9. 4. Henriques JP, Zijlstra F, Ottervanger JP, de Boer MJ, van‘t Hof AW, Hoorntje JC, et al. Incidence and clinical significance of distal embolization during primary angioplasty for acute myocardial infarction. Eur Heart J. 2002;23:1112–1117. 5. Fokkema ML, Vlaar PJ, Svilaas T, Vogelzang M, Amo D, Diercks GF, et al. Incidence and clinical consequences of distal embolization on the coronary angiogram after percutaneous coronary intervention for ST-elevation myocardial infarction. Eur Heart J. 2009;30:908–15. 6. Dong-bao L, Qi H, Zhi L, Shan W, Wei-ying J. Predictors and short-term prognosis of angiographically detected distal embolization after emergency percutaneous coronary intervention for ST-elevation acute myocardial infarction. Clin Res Cardiol. 2009;98:773–9. 7. Ndrepepa G, Tiroch K, Keta D, Fusaro M, Seyfarth M, Pache J, et al. Predictive factors and impact of no reflow after primary percutaneous coronary intervention in patients with acute myocardial infarction. Circ Cardiovasc Interv. 2010;3:27–33. 8. Ndrepepa G, Tiroch K, Fusaro M, Keta D, Seyfarth M, Byrne RA, et al. 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol. 2010;55:2383–9.

9. Dong-bao L, Qi H, Zhi L, Shan W, Wei-ying J. Predictors and long-term prognosis of angiographic slow/no-reflow phenomenon during emergency percutaneous coronary intervention for STelevated acute myocardial infarction. Clin Cardiol. 2010;33:E7–12. 10. Chan W, Stub D, Clark DJ, Ajani AE, Andrianopoulos N, Brennan AL, et al. Usefulness of transient and persistent no reflow to predict adverse clinical outcomes following percutaneous coronary intervention. Am J Cardiol. 2012;109:478–85. 11. Limbruno U, Micheli A, De Carlo M, Amoroso G, Rossini R, Palagi C, et al. Mechanical prevention of distal embolization during primary angioplasty: safety, feasibility, and impact on myocardial reperfusion. Circulation. 2003;108:171–6. 12. Yip HK, Wu CJ, Chang HW, Fang CY, Yang CH, Chen SM, et al. Effect of the percusurge guardwire device on the integrity of microvasculature and clinical outcomes during primary transradial coronary intervention in acute myocardial infarction. Am J Cardiol. 2003;92:1331–5. 13. Stone GW, Webb J, Cox DA, Brodie BR, Qureshi M, Kalynych A, et al. Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial. JAMA. 2005;293:1063–72. 14. Gick M, Jander N, Bestehorn HP, Kienzle RP, Ferenc M, Werner K, et al. Randomized evaluation of the effects of filter-based distal protection on myocardial perfusion and infarct size after primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation. Circulation. 2005;112:1462–9. 15. Bartorelli AL, Koh TH, Di Pede F, Reimers B, Thuesen L, Amann FW, et al. Distal embolic protection during percutaneous coronary intervention in patients with acute coronary syndromes: the RUBY study. Acute Card Care. 2006;8:148–54. 16. Kaltoft A, Bottcher M, Nielsen SS, Hansen HH, Terkelsen C, Maeng M, et al. Routine thrombectomy in percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction: a randomized, controlled trial. Circulation. 2006;114:40–7. 17. Cura FA, Escudero AG, Berrocal D, Mendiz O, Trivi MS, Fernandez J, et al. Protection of distal embolization in high-risk patients with acute ST-segment elevation myocardial infarction (PREMIAR). Am J Cardiol. 2007;99:357–63. 18. Zhou BQ, Tahk SJ. Effect of a distal protection device on epicardial blood flow and myocardial perfusion in primary percutaneous coronary intervention. J Zhejiang Univ Sci B. 2007;8:575–9. 19. Muramatsu T, Kozuma K, Tsukahara R, Ito Y, Fujita N, Suwa S, et al. Comparison of myocardial perfusion by distal protection before and after primary stenting for acute myocardial infarction: angiographic and clinical results of a randomized controlled trial. Catheter Cardiovasc Interv. 2007;70:677–82. 20. Bavry AA, Kumbhani DJ, Bhatt DL. Role of adjunctive thrombectomy and embolic protection devices in acute myocardial infarction: a comprehensive meta-analysis of randomized trials. Eur Heart J. 2008;29:2989–3001. 21. Mamas MA, Fraser D, Fath-Ordoubadi F. The role of thrombectomy and distal protection devices during percutaneous coronary interventions. EuroIntervention. 2008;4:115–23. 22. Kelbaek H, Terkelsen CJ, Helqvist S, Lassen JF, Clemmensen P, Klovgaard L, et al. Randomized comparison of distal protection versus conventional treatment in primary percutaneous coronary intervention: the drug elution and distal protection in st-elevation myocardial infarction (DEDICATION) trial. J Am Coll Cardiol. 2008;51:899–905. 23. Kaltoft A, Nielsen SS, Terkelsen CJ, Bottcher M, Lassen JF, Krusell LR, et al. Scintigraphic evaluation of routine filterwire distal protection in percutaneous coronary intervention for acute

123

T. Fujii et al. ST-segment elevation myocardial infarction: a randomized controlled trial. J Nucl Cardiol. 2009;16:784–91. 24. Jin B, Dong XH, Zhang C, Li Y, Shi HM. Distal protection devices in primary percutaneous coronary intervention of native coronary artery lesions: a meta-analysis of randomized controlled trials. Curr Med Res Opin. 2012;28:871–6. 25. Ikari Y, Sakurada M, Kozuma K, Kawano S, Katsuki T, Kimura K, et al. Upfront thrombus aspiration in primary coronary intervention for patients with st-segment elevation acute myocardial infarction: report of the vampire (VAcuuM asPIration thrombus REmoval) trial. JACC Cardiovasc Interv. 2008;1:424–31. 26. Lefevre T, Garcia E, Reimers B, Lang I, di Mario C, Colombo A, et al. X-sizer for thrombectomy in acute myocardial infarction improves ST-segment resolution: results of the x-sizer in ami for negligible embolization and optimal st resolution (X AMINE ST) trial. J Am Coll Cardiol. 2005;46:246–52. 27. Vlaar PJ, Svilaas T, van der Horst IC, Diercks GF, Fokkema ML, de Smet BJ, et al. Cardiac death and reinfarction after 1 year in the thrombus aspiration during percutaneous coronary intervention in acute myocardial infarction study (TAPAS): a 1-year follow-up study. Lancet. 2008;371:1915–20. 28. Srinivasan M, Rihal C, Holmes DR, Prasad A. Adjunctive thrombectomy and distal protection in primary percutaneous coronary intervention: impact on microvascular perfusion and outcomes. Circulation. 2009;119:1311–9. 29. Isshiki T, Kozuma K, Kyono H, Suzuki N, Yokoyama N, Yamamoto Y. Initial clinical experience with distal embolic protection using ‘‘filtrap’’, a novel filter device with a selfexpandable spiral basket in patients undergoing percutaneous coronary intervention. Cardiovasc Interv Ther. 2011;26:12. 30. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third universal definition of myocardial infarction. Circulation. 2012;126:2020–35. 31. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, et al. Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation. 1987;76:142–54.

123

32. Topol EJ, Yadav JS. Recognition of the importance of embolization in atherosclerotic vascular disease. Circulation. 2000;101:570–80. 33. Gorog DA, Foale RA, Malik I. Distal myocardial protection during percutaneous coronary intervention: when and where? J Am Coll Cardiol. 2005;46:1434–45. 34. Ito H. The no-reflow phenomenon associated with percutaneous coronary intervention: Its mechanisms and treatment. Cardiovasc Interv Ther. 2011;26:2. 35. Stone GW, Rogers C, Hermiller J, Feldman R, Hall P, Haber R, et al. Randomized comparison of distal protection with a filterbased catheter and a balloon occlusion and aspiration system during percutaneous intervention of diseased saphenous vein aorto-coronary bypass grafts. Circulation. 2003;108:548–53. 36. Matsuo A, Inoue N, Suzuki K, Nakamura R, Fujita H, Miki S, et al. Limitations of using a guardwire temporary occlusion and aspiration system in patients with acute myocardial infarction: multicenter investigation of coronary artery protection with a distal occlusion device in acute myocardial infarction (MICADO). J Invasive Cardiol. 2007;19:132–8. 37. Limbruno U, De Caterina R. EMERALD, AIMI, and PROMISE: is there still a potential for embolic protection in primary PCI? Eur Heart J. 2006;27:1139–45. 38. Svilaas T, Vlaar PJ, van der Horst IC, Diercks GF, de Smet BJ, van den Heuvel AF, et al. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med. 2008;358:557–67. 39. Jang IK, Tearney GJ, MacNeill B, Takano M, Moselewski F, Iftima N, et al. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation. 2005;111:1551–5. 40. Endo M, Hibi K, Shimizu T, Komura N, Kusama I, Otsuka F, et al. Impact of ultrasound attenuation and plaque rupture as detected by intravascular ultrasound on the incidence of noreflow phenomenon after percutaneous coronary intervention in ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2010;3:540–9.

Impact of transient or persistent slow flow and adjunctive distal protection on mortality in ST-segment elevation myocardial infarction.

Routine use of distal protection for ST-segment elevation myocardial infarction (STEMI) is not recommended. The purpose of this study was to analyze t...
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