American Journal of Emergency Medicine (2012) 30, 1118-1124

Original Contribution

Superior outcome with direct catheter laboratory access vs ED-activated primary percutaneous coronary intervention^?,??

Bikash Majumder ^a,?, Chrysostomos Mavroudis ^b, Colette Smith PhD ^c, John G. Coghlan MD ^b, ManFai Shiu MD ^b, Roby D. Rakhit MD ^b

^aDepartment of Cardiology, University Hospital Wales, Cardiff, CF14 4XW, UK

^bDepartment of Cardiology, Royal Free Hospital, London NW3 2QG, UK

^cResearch Department of Infection and population health, University College London Medical School, Royal Free Hospital, London, NW3 2QG, UK

Received 14 May 2011; revised 28 June 2011; accepted 15 July 2011

Abstract

Aims: Admitting patients directly to a heart attack center (HAC) catheter laboratory for Primary percutaneous coronary intervention bypassing the emergency department (ED) might be beneficial in delivering treatment of ST-elevation myocardial infarction with superior outcome.

Methods: In this analysis, the clinical outcome of service redesign of the PPCI pathway from ED triggered to a direct catheter laboratory HAC access was assessed in 361 consecutive patients with ST-elevation myocardial infarction treated with a PPCI.

Results: A total of 200 patients were admitted via the ED, and 161 were admitted directly to the HAC. Door-to-balloon times and call-to-balloon times were significantly better in the HAC group (median [interquartile range] door-to-balloon times and call-to-balloon times were 39 [26, 53] and 106 [91, 132]

minutes, respectively) in comparison with the ED group (82 [49,120; P b .0001] and 130 [103, 164] minutes, respectively [P = .0005]). A nonsignificant trend to a lower 30-day (5% in the HAC group and 6% in the ED group) and 17-month (8% in HAC group and 11% in ED group) mortality was seen in the HAC group (P = .63). Composite end point analysis of left ventricular ejection fraction less than 50%, thrombolysis in myocardial infarction grades 0 and 1, and myocardial blush scores 0 and 1 showed that a significantly higher number of patients in the ED group experienced at least 1 of the composite events in comparison with the patients in the HAC group (P = .01).

Conclusion: A direct-access catheter laboratory (HAC) model of PPCI bypassing the ED should be the favored approach to service delivery with superior outcome.

(C) 2012

^? Place of study: Department of Cardiology, Royal Free Hospital, Pond Street, NW3 2QG London, UK.

^?? Competing interest statement: The authors have no competing

interest to declare.

* Corresponding author. Tel.: +44 0 7823886632; fax: +44 0 2920743147.

E-mail address: [email protected] (B. Majumder).

Introduction

Primary percutaneous coronary intervention (PPCI) is considered to be superior to thrombolysis in the treatment of ST-elevation myocardial infarction by reducing the

0735-6757/$ - see front matter (C) 2012 doi:10.1016/j.ajem.2011.07.016

combined end point of death and recurrent myocardial infarction [1,2]. Many [3-6] but not all [7,8] studies have shown a higher mortality associated with the delay in reperfusion. The CADILLAC trial has shown that early reperfusion (b3 hours) with PPCI for STEMI is associated with superior outcome, with lower mortality at both 30 days and 1 year [9]. Early reperfusion-enhanced microvascular reperfusion, evidenced by a higher frequency of grade 2 to 3 myocardial blush, was associated with a higher frequency of complete ST-segment resolution and better recovery of left ventricular function. Delay in reperfusion impacts on mortality in high-risk patients (such as those with Killip class 2-3, anterior infarct, age N70 years, or Renal impairment). Very early reperfusion improves survival by enhancing myocardial salvage. Myocardial salvage and recovery of left ventricular function is greatest when reperfusion is achieved within 2 hours of symptom onset [3,10]. There is a suggestion that delays in door-to-balloon time may be associated with poorer outcomes. Registry data from Mcnamara et al [11] noted a strong relationship between door-to-balloon time and in-hospital mortality among 29 222 patients with STEMI. Adjusting for differ- ences in patient characteristics, they showed that patients with door-to-balloon time greater than 90 minutes had increased mortality compared with those who had a door-to- balloon time of 90 minutes or less.

Because delay in reperfusion adversely affects outcome, a coordinated approach is necessary so that patients can access a Cardiac intervention center as quickly as possible [12]. Data suggest that in-hospital mortality is very low and reperfusion is rapid and effective in a strategy where paramedics independently diagnose and refer patients with STEMI in a designated center for PPCI [13]. The emergency department (ED) remains the traditional access route into an acute hospital where initial assessment is performed before PPCI. However, this route normally involves noncardiologists and may lead to delay. Steg et al

[14] in USIC 2000 registry demonstrated that bypassing the ED reduced the delay and mortality regardless of type of Reperfusion strategy used. Similarly, Bang et al [15] have demonstrated short-term and longer-term Mortality benefit with direct admission to coronary care unit com- pared with the ED admission, as the reperfusion was quicker in the coronary care unit group.

Background

Primary percutaneous coronary intervention replaced thrombolysis as the reperfusion strategy for STEMI in our institution (Royal Free Hospital NHS Trust) in 2005. As a large teaching hospital with an ED, the PPCI pathway was initially activated via the ED, with all patients with confirmed STEMI being delivered by paramedic crews to the ED with subsequent mobilization of the catheter

Fig. 1 Primary percutaneous coronary intervention pathways.

laboratory team. However, in 2007, we redesigned the service to accept patients directly to our catheter laboratory bypassing the traditional admission route via the ED. Patients with confirmed STEMI, diagnosed by trained ambulance paramedics at home, are brought 24 hours a day 7 days a week directly to a dedicated “Heart Attack Centre” (HAC) entrance adjacent to the catheter laboratory. Similarly, if patients with STEMI within 12 hours of symptom onset present to the ED of an adjoining district general hospital without a percutaneous coronary interven- tion (PCI) facility, the ED physician activates the PPCI call and arranges immediate Ambulance transfer to our HAC. The aim of this study was to compare the efficacy and outcome of PPCI activated via the ED with direct catheter laboratory access (Fig. 1).

Methods

In this retrospective study, 361 consecutive patients from North Central London area who underwent Primary percutaneous intervention for STEMI between the period of January 2006 and September 2008 were reviewed. Patients were divided broadly into 2 groups: group 1, patients who were admitted directly to the catheterization laboratory via the HAC entrance, and group 2, patients who were first admitted via the ED of our hospital. Each of these groups was further subdivided to include the Interhospital transfer patients from the adjoining district general hospitals. The median follow-up period was 17 months.

Prehospital care

According to the standard protocol, all patients had a 12- lead electrocardiogram by paramedic crew. After diagnosis, patients with acute myocardial infarction received 300 mg of

aspirin in the ambulance. Paramedics also obtained intrave- nous access, administered Intravenous morphine and meto- clopropamide, and administered oxygen. All the patients were loaded with 300 mg of clopidogrel on arrival at the hospital before PPCI. Patients also received weight-adjusted unfractionated heparin just before the commencement of PPCI procedure.

Primary end points

The primary end point was to assess any difference in door-to-balloon and call-to-balloon times between these 2 groups. The door-to-balloon and call-to-balloon times were recorded according to Myocardial Ischaemia National Audit Project criteria, incorporating London Ambulance electronic records [16].

Secondary end points

Secondary end points included 30-day mortality, medi- um-term mortality, Thrombolysis in Myocardial Infarction flow, myocardial blush score, left ventricular ejection fraction (LVEF), and 12-hour Creatinine kinase and troponin T levels. Mortality data were collected via the National Strategic Tracing Service database.

All coronary angiograms were reviewed to assess postprocedural TIMI flow and myocardial blush score. Angiogram reviewers were blinded to the groups. Myocar- dial blush score [17] and TIMI flow [18,19] were assessed as previously described. Left ventricular ejection fraction was obtained from echocardiography reports.

Statistical analysis

For comparisons of categorical variables between groups,

P values were calculated using the ?2 test or the Fisher exact

test when the expected number in any cell was less than 5. For continuous variables, P values were calculated using unpaired t tests and analysis of variance for normally distributed data and using Mann-Whitney U test and Kruskal-Wallis tests for nonnormally distributed data. A log-rank test using a survival analysis approach was used to assess Survival benefit between the 2 groups. The relation- ship between call-to-balloon and door-to-balloon times with 30-day mortality was summarized using an odds ratio. All P values are 2 sided and were calculated using SAS, version

9.0 (SAS Institute Inc, Cary, NC).

Results

Fig. 2 describes the source of patients with PPCI and admission route. All patients in the HAC and ED groups were taken to the hospital by the London Ambulance Service.

Baseline characteristics

Baseline characteristics of the patients are described in Table 1. In the ED group, a significantly higher number of patients had a culprit lesion in the left anterior descending artery, and patients in this group had a longer follow-up. This was expected, as in general, patients admitted via the ED were treated in earlier calendar years.

Door-to-balloon time, call-to-balloon time, length of stay

In the HAC group, the median (interquartile range, or IQR) door-to-balloon and call-to-balloon times were signif- icantly better than those of the ED group (P b .0001 and P =

.0005, respectively; Table 2). Excluding the interhospital transfer patients from both the groups, 100 (100%) of the HAC patients achieved a call-to-balloon time less than 3

Fig. 2 Patient distribution according to admission route.

HAC		ED	Total	P
No.	161 (100.0%)	200 (100.0%)	361 (100%)
Age (y), median (95% CI)	62 (60-64)	64 (63-66)	63 (62-65)	.10
Sex (male)	135 (83.8%)	152 (76.0%)	287	.07
History of hypertension	59/114 (51.8)	88/141 (62.4)	147/255 (57.6%)	.09
History of hypercholesterolemia	55/108 (50.9%)	87/131 (66.4%)	142/239 (59.4%)	.02
History of smoking	70/100 (70.0%)	76/131 (58.0%)	146/231 (63.2%)	.06
History of diabetes	23/109 (21.1%)	36/158 (22.8%)	59/267 (22.1%)	.74
Follow-up (mo), median (IQR)	10 (7, 14)	24 (18, 27)	17 (10, 25)	b.0001
Right coronary artery	76 (47.2%)	70 (35%)	146 (40.4%)	.02
left circumflex artery	23 (14%)	24 (12%)	47 (13.01%)	.52
left anterior descending artery	59 (36.6%)	106 (53%)	165 (45.7%)	.002
Not available	3 (1.8%)	0	3 (0.8%)	.09

hours compared with 135 (86.5%) of the ED group. There was no significant difference in the median (IQR) length of hospital stay in these 2 groups. However, a higher number of patients in the ED admission group spent more than 5 days in the hospital (Table 2).

Table 1 Baseline characteristics of the patients in ED and HAC

Outcome data

In the entire study group, 20 (5.6%) of the 361 patients died within 30 days, and 35 (9.6%) patients died during the entire follow-up period. There was no significant difference in 30-day mortality between the 2 groups (Table 3). A log- rank test using a survival analysis approach showed a trend of better survival in the HAC group, but the difference was not statistically significant (P = .63; Fig. 3). A total of 13 (8%) patients in the HAC group and 22 (11%) patients in the ED group died during the follow-up period. There were no significant differences in TIMI flow, myocardial blush score, and LVEF between these 2 groups (Table 3).

To understand the effect of time delay on mortality, the relationship between call-to-balloon time, door-to-balloon

Table 2 Comparison of outcome data

time, and 30-day mortality was summarized using an odds ratio. Every 1-hour delay in call-to-balloon time was associated with an odds ratio of 30-day mortality of 1.04 (95% confidence interval [CI], 0.62-1.74; P = .90), and every 1-hour delay in door-to-balloon time was associated with an odds ratio of 30-day mortality of 1.13 (95% CI, 0.69- 1.86; P = .62). Thus, the odds of death within 30 days increased by 4% for every 1-hour delay in call-to-balloon time and 13% for every 1-hour delay in door-to-balloon time, although these results did not meet statistical significance and the confidence intervals were imprecise.

Composite end point analysis

A total of 109 patients experienced at least 1 of a composite end point of 30-day mortality, LVEF less than 50%, TIMI grades 0 and 1, blush scores 0 and 1. A significantly higher number of patients (66 patients) in the ED group experienced at least 1 of the events included in the composite end points in comparison with the HAC group patients (43 patients; P = .01). In the group of patients who

HAC		ED	Total	P
Call-to-balloon time b3 h, yes	145 (90.1%)	171 (85.5%)	316 (87.5%)	.19
Call-to-balloon time (min), median (IQR)	106 (91, 132), n = 117	130 (103, 164), n = 145	121 (95, 156), n = 262	.0005
Door-to-balloon time (min)
<=30	42/132 (31.8%)	12/165 (7.3%)	54/297 (18.2%)	b.0001
31-60	65/132 (49.2%)	47/165 (28.5%)	112/297 (37.7%)
61-90	18/132 (13.6%)	31/165 (18.8%)	49/297 (16.5%)
N90	7/132 (5.3%)	75/165 (45.5%)	82/297 (27.6%)
Door-to-balloon time (min), median (IQR)	39 (26, 53)	82 (49, 120)	53 (36, 98)	.0005
Time spent in hospital (d)
1	43/160 (26.9%)	51/197 (25.9%)	94/357 (26.3%)	.52
2	56/160 (35.0%)	56/197 (28.4%)	112/357 (31.4%)
3	28/160 (17.5%)	35/197 (17.8%)	63/357 (17.6%)
4 or 5	17/160 (10.6%)	27/197 (13.7%)	44/357 (12.3%)
N5	16/160 (10.0%)	28/197 (14.2%)	44/357 (12.3%)
Time spent in hospital (d), median (IQR)	2 (1, 3), n = 160	2 (1, 4), n = 197	2 (1, 3), n = 357	.10

HAC		ED	Total	P
Myocardial blush grade
0	3/113 (2.7%)	0/70 (0.0%)	3/183 (1.6%)	.41
1	12/113 (1.6%)	4/70 (5.7%)	16/183 (8.7%)
2	26/113 (23.0%)	18/70 (25.7%)	44/183 (24.0%)
3	72/113 (63.7%)	48/70 (68.6%)	120/183 (65.6%)
TIMI flow grade
0	1/124 (0.8%)	0/84 (0.0%)	1/208 (0.5%)	.78
1	4/124 (3.2%)	1/84 (1.2%)	5/208 (2.4%)
2	19/124 (15.3%)	15/84 (17.9%)	34/208 (16.3%)
3	100/124 (80.7%)	68/84 (81.0%)	168/208 (80.8%)
Dead within 30 d: yes	8/161 (5.0%)	12/200 (6.0%)	20/361 (5.6%)	.82
LVEF, median (IQR)	55 (45, 60), n = 82	50 (40, 55), n = 122	50 (45, 55), n = 204	.09

experienced the composite end point, the median (IQR) door-to-balloon time was significantly higher, that is, 60 (39, 93) minutes, in comparison with the group who did not experience the composite end point, that is, 39 (28, 80) minutes (P = .04), whereas there was no significant difference in call-to-balloon time between these 2 groups.

Table 3 Comparison of clinical outcome

Discussion

In a Pooled analysis of 1199 patients from 4 contemporary PPCI trials, infarct size was smallest when symptom-to- balloon time was less than 2 hours, intermediate with 2- to 3- hour delay, and largest with 3-hour delay or more [20]. Therefore, a prerequisite for a contemporary PPCI service is one that offers early paramedic-led diagnosis of myocardial infarction and immediate transfer directly to a catheter laboratory, thus avoiding the inherent delay associated with preliminary assessment in the ED.

This retrospective study has clearly showed a significant benefit in the call-to-balloon and door-to-balloon times by implementing this strategy. Only 5.3% of the patients who were admitted directly to the catheter laboratory had a door-to- balloon time more than 90 minutes compared with 45.5% of the patients admitted via the ED route. This suggests that

Fig. 3 Log-rank analysis showing better survival in the HAC group.

patients who are not received directly in the catheter laboratory can experience a significant delay. Sixty-one patients in the HAC admission group initially presented to the adjoining district general hospital, and despite the delay associated with their transfer to the catheter laboratory, the median call-to- balloon time was 106 minutes. This was only possible because of a service model that allows the ED physician in the district general hospital to activate the PPCI call without the need for further discussion with the local cardiology or medical teams, minimizing unnecessary delay. This integrated approach has resulted in low mortality associated with PPCI. Thirty-day mortality was 5% in the HAC group and 6% in the ED group, giving the overall mortality of 5.6%, which is comparable with other published data [21,22]. There was no significant difference in TIMI flow and myocardial blush score between the 2 groups despite the fact that there was a significant delay in door-to-balloon and call-to-balloon times in the patients admitted via the ED. These results are consistent with the findings in the CADILLAC trial, where door-to-balloon time had no significant effect on the frequency of achieving TIMI 3 flow or grade 2 to 3 myocardial blush post-PCI [9]. Brodie et al

[3] demonstrated that an incremental time delay in treating patients with PPCI had a major effect in 30-day mortality in the early hours after the onset of acute myocardial infarction (<=3 hours) but less effect in the later hours (N3 hours). There was little difference in mortality on whether reperfusion was achieved at 3 to 6 hours or more than 6 hours. This nonlinearity is in sharp contrast with thrombolytic therapy probably because after thrombolysis, TIMI 3 flow rate decreases with increasing time to treatment, whereas after PPCI, TIMI 3 flow rate is much higher regardless of time of treatment [8]. In our study, though, 87.5% of the patients had a call-to-balloon time less than 3 hours; we found that the odds of death within 30 days increased by 4% for every 1-hour delay in call-to-balloon time and by 13% for every 1-hour delay in door-to-balloon time. Although no significant difference in mortality at 30 days and medium-term follow-up (median follow-up, 17 months) was seen between the ED admission group and the HAC group, a significant number of patients in the ED group had experienced at least 1 of the composite end points in

comparison with the HAC group. Patients who experienced a composite end point had a significantly higher door-to-balloon time in comparison with the patients who did not experience any of the composite end points. This illustrates the importance of reducing the delay within the hospital to treat the acute STEMI effectively. The nonsignificant difference in mortality could be explained by the fact that patients from both groups achieved similar rate of TIMI 3 flow, and mortality was too low to achieve any statistical significance.

Conclusion

Direct cardiac catheter laboratory (HAC) access is a preferred model for a contemporary PPCI service. Admitting patients first to the ED before PPCI causes delay and may be associated with worse outcomes. Service redesign within our institution has allowed us to admit patients directly to the cardiac catheterization laboratory bypassing the traditional ED admission approach. This has significantly improved door-to- balloon time and call-to-balloon time performance and streamlined the treatment pathway for patients with acute STEMI. A nonsignificant difference is seen in mortality in favor of a HAC approach. A composite end point including 30-day mortality, LVEF less than 50%, TIMI grades 0 and 1, and blush score 0 and 1 occurred more frequently in the ED admission group compared with the HAC group, with an associated higher median door-to-balloon time in the group that experienced at least 1 of the composite end points. It reemphasizes the importance of adopting an integrated approach in the treatment of acute myocardial infarction with PPCI by accepting the patients directly to the HAC from the community, to avoid unnecessary delay both outside and within the hospital.

Study limitations

This is a retrospective analysis and with quite a small sample size. This may explain why a significant difference in performance as measured by door-to-balloon and call-to- balloon times did not directly correlate with clear differences in individual outcome data.

Acknowledgment

The authors acknowledge the contribution of Ms Katie Worrall and Dr Ramadan Abdelgawad in collecting data.

References

1. Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA 1997;278:2093-8.
2. Keeley EC, Boura JA, Grines CL. primary angioplasty versus intravenous thrombolysis therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13-20.
3. Brodie BR, Stuckey TD, Wall TC, et al. Importance of time to reperfusion for 30 day and late survival and recovery of left ventricular function after primary angioplasty for acute myocardial infarction. J Am Coll Cardiol 1998;32:1312-9.
4. Cannon CP, Gibson CM, Lambrew CT, et al. Relationship of symptom onset- to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA 2000;283:2941-7.
5. Antoniucci D, Valenti R, Migliorini A, et al. Relation of time to treatment and mortality in patients with myocardial infarction undergoing primary coronary angioplasty. Am J Cardiol 2002;89:1248-52.
6. De Luca G, Suryapranata H, Zijlstra F, et al. Symptom-onset-to- balloon time and mortality in patients with acute myocardial infarction in patients with acute myocardial infarction treated by primary angioplasty. J Am Coll Cardiol 2003;42:991-7.
7. Berger PB, Ellis SG, Holmes DR, et al. Relationship between delay in performing direct coronary angioplasty and early clinical outcomes in patients with acute myocardial infarction: results from GUSTO-IIb trial. Circulation 1999;100:14-20.
8. Brudie BR, Stone GW, Morice MC, et al. Importance of time to reperfusion on outcomes with primary coronary angioplasty for acute myocardial infarction: results from the stent primary angioplasty in myocardial infarction trial. Am J Cardiol 2001;88:1085-90.
9. Brodie BR, Stone GW, Cox DA, et al. Impact of treatment delays on outcome of primary percutaneous coronary intervention for acute myocardial infarction: analysis from the CADILAC trial. Am Heart J 2006;151:1231-8.
10. Milavetz JJ, Giebel DW, Christian TF, et al. Time to therapy and salvage in myocardial infarction. J Am Coll Cardiol 1998;31:1246-51.
11. Mcnamara RL, Wang Y, Herrin J, et al. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2006;47:2180-6.
12. De Luca G, Suryapranata H, Ottervanger JP, et al. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation 2004;109: 1223-5.
13. Le May MR, Davies RF, Dionne R, et al. Comparison of early mortality of paramedic-diagnosed ST-segment elevation myocardial infarction with immediate transport to a designated primary percuta- neous coronary intervention centre to that of similar patients transported to the nearest hospital. Am J Cardiol 2006;98:1329-33.
14. Steg PG, Cambou JP, Goldstein P, et al. Bypassing the emergency room reduces delays and mortality in ST elevation myocardial infarction: the USIC 2000 registry. Heart 2006;92:1378-83.
15. Bang A, Grip L, Herlitz J, et al. Lower mortality after Prehospital recognition and treatment followed by fast tracking to coronary care compared with admittance via emergency department in patients with ST-elevation myocardial infarction. Int J Cardiol 2008;129: 325-32.
16. Herrett E, Smeeth L, Walker L, et al. On behalf of the MINAP Academic Group. The Myocardial Ischaemia National Audit Project (MINAP). Heart 2010;96:1264-7.
17. Van’t Hof AWJ, Liem A, Suryapranata H, et al. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction. Myocardial blush grade. Circulation 1998;97:2302-6.
18. Chesebro JH, Knatteurd G, Roberts R, et al. Thrombolysis In Myocardial Infarction trial, Phase 1: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation 1987;76:142-54.
19. De Boer MJ, Rieber JHC, Suryapranata H, et al. angiographic findings and catheterisation laboratory events in patients with primary coronary angioplasty or streptokinase therapy for acute myocardial infarction. Eur Heart J 1995;16:1347-56.
20. Stone GW, Dixon SR, Grines CL, et al. Predictors of infarct size after primary coronary angioplasty in acute myocardial infarction from pooled analysis from four contemporary trials. Am J Cardiol 2007; 100:1370-5.
21. Boersma E, and the Primary Coronary Angioplasty vs Thrombolysis (PCAT)-2 Trialists’ Collaborative Group. Does time matter? A pooled analysis of randomized clinical trials comparing primary percutaneous

intervention and in-hospital fibrinolysis in Acute myocardial infarction patients. Eur Heart J 2006;27:779-88.

1. Zijlstra F, Patel A, Jones M, et al. Clinical characteristics and outcome of patients with early (b2 h), intermediate (2-4 h) and late (N4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction. Eur Heart J 2002;23:550-7.