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Archives of cardiovascular diseases
Volume 105, n° 12
pages 639-648 (décembre 2012)
Doi : 10.1016/j.acvd.2012.07.007
Received : 24 April 2012 ;  accepted : 27 July 2012
Impact of transfer time on mortality in acute coronary syndrome with ST-segment elevation treated by angioplasty
Impact du temps de transfert sur la mortalité dans le syndrome coronaire aigu avec sus-décalage du segment ST traité par angioplastie primaire

Johanne Silvain a, Jean-Baptiste Vignalou a, Farzin Beygui a, Stephen A. O’Connor a, Olivier Barthélémy a, Franck Boccara b, Patrick Ecollan c, Jean-Philippe Collet a, Patrick Assayag d, Gilles Montalescot a,
a Institut de Cardiologie, Inserm CMR937, Pitié-Salpêtrière Hospital (AP–HP), Université Paris 6, Paris, France 
b Service de Cardiologie, Saint-Antoine Hospital (AP–HP), Université Paris 6, Paris, France 
c SMUR, Pitié-Salpêtrière Hospital (AP–HP), Université Paris 6, Paris, France 
d Service de Cardiologie, Bicêtre Hospital (AP–HP), Université Paris 11, Paris, France 

Corresponding author. Bureau 236, Institut de Cardiologie, Pitié-Salpêtrière Hospital, 47-83 boulevard de l’Hôpital, 75013 Paris.

In primary percutaneous coronary intervention (pPCI), conflicting data exist on the relative importance of patient presentation time (time from symptom onset (SO) to first medical contact [FMC]) and transfer time (time from FMC to sheath insertion).


To evaluate the impact of transfer time on mortality in an unselected ST-elevation myocardial infarction (STEMI) population treated with pPCI.


In a well-organized urban network, using mobile intensive care units (MICU) whenever possible, the impact of transfer time on inhospital mortality was evaluated in 703 unselected consecutive STEMI patients transferred for pPCI.


Our STEMI population included patients with cardiogenic shock (5.3%) and out-of-hospital cardiac arrest (3.7%). Longer transfer times were found to be associated with a stepwise increase in mortality ranging from 2.99% in the first quartile (Q1) up to 8.65% in the fourth quartile (Q4) (P =0.005). This result was noted in patients presenting early (≤2h of SO, 0.96% for Q1 vs. 9.8% for Q4, P =0.006) but not in late presenters (>2h of SO, 7.00% for Q1 vs. 7.8% for Q4, P =0.85). After adjustment for confounding variables such as the severity of patients, the relationship between mortality and transfer time was no longer apparent.


In a well-organized urban network dedicated to pPCI, including unselected STEMI patients, transfer time does not appear to be a major contributor to mortality. The relationship of transfer time to mortality seems to be dependent on presentation time and patients’ clinical severity.

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Il existe peu de données sur l’importance pronostique relative du délai de présentation du patient (début des symptômes [DS] – premier contact médical) et du temps de transfert (premier contact médical-insertion du désilet) dans le SCA ST+traité par angioplastie primaire (AP).


Évaluer l’impact indépendant du temps de transfert sur la mortalité intrahospitalière dans le SCA ST+traité par AP.

Matériel et méthodes

Dans un réseau urbain organisé utilisant le SAMU, l’impact du temps de transfert sur la mortalité intrahospitalière a été évalué chez 703 patients SCA ST+ non sélectionnés transférés pour AP.


La population de l’étude comprenait des chocs cardiogéniques (5,3 %) et des arrêts cardiaques extrahospitaliers (3,7 %). L’allongement du temps de transfert était associé à une augmentation progressive de la mortalité (2,99 % pour le premier quartile [Q1] jusqu’à 8,65 % pour le quatrième quartile [Q4]; p =0,005). Cette relation était encore plus marquée chez les patients se présentant précocement (≤2h du DS, 0,96 % pour Q1 vs 9,8 % pour Q4; p =0,006), mais non significative pour les patients se présentant tardivement (>2h du DS, 7,00 % pour Q1 vs 7,8 % pour Q4; p =0,85). En analyse multivariée, le temps de transfert n’était plus associé à la mortalité.


Dans un réseau urbain organisé dédié à l’AP, le temps de transfert ne semble pas être un déterminant majeur de la mortalité. La relation entre le temps de transfert et la mortalité précoce apparaît fortement dépendante du délai de présentation et de la sévérité clinique.

The full text of this article is available in PDF format.

Keywords : Myocardial Infarction, Angioplasty, Door-to-balloon, Transfer Time

Mots clés : Infarctus du myocarde, Angioplastie, Délai, Temps de transfert

Abbreviations : D2B, ED, FMC, IQR, MICU, PCI, pPCI, SO, STEMI, TIMI


European and American guidelines support primary percutaneous coronary intervention (pPCI) as the treatment of choice for patients with acute ST-segment elevation myocardial infarction (STEMI), especially when delivered within 12hours of symptom onset (SO) [1, 2]. Despite guidelines and quality improvement programmes, reducing time to reperfusion in STEMI patients remains important but challenging [3]. Numerous studies, including randomized trials and meta-analyses, have investigated the benefits of reducing ischaemic time in STEMI patients treated with pPCI. Most have suggested a benefit in reducing time to reperfusion to salvage the myocardium involved, subsequently lowering the risk of death [4]. Factors delaying time to reperfusion in pPCI have been identified, but vary according to countries, populations and facilities of the STEMI networks involved [5, 6]. Moreover, little is known about the importance of the relationship between patient presentation time (the time from SO to first medical contact [FMC]) and transfer time (the time from FMC to sheath insertion). Field triage appears to be a useful approach for reducing transfer time [7] and allowing fast delivery of prehospital pharmacological therapies, thus potentially improving outcomes after pPCI [8]. The French Health Care System has been using field triage with mobile intensive care units (MICUs) for a long time. An on-board physician, trained in the diagnosis of acute myocardial infarction, triages the patients and facilitates rapid transfer to a pPCI centre (direct transfer) while at the same time, administers prehospital antiplatelet therapy loading and anticoagulation. This system is predominant in Paris, with full coverage of the city area where pPCI is the exclusive mode of reperfusion for STEMI.

While it would seem logical that a reduction in the time from FMC to catheterization (transfer time) would result in improved mortality through reduced ischaemic time, the translation of this general finding in our specific urban STEMI network using MICUs routinely remains uncertain. Additionally, determinants of mortality such as presentation time are often not considered in studies of time delays for pPCI and the most severe patients are often excluded from such analyses. We therefore tested the hypothesis that transfer time for pPCI is still a major contributor to inhospital death in our specific STEMI network. For that purpose, we evaluated the independent impact of transfer time on inhospital mortality in unselected consecutive STEMI patients routinely treated with pPCI in a high-volume PCI centre.

Study design and patient population

Consecutive patients admitted for pPCI at the catheterization laboratory of the Pitié-Salpêtrière University Hospital, Paris (France) between June 2004 and February 2007 were included in the e-PARIS registry, a web-based registry used to gather data from patients referred to our institution. Patients discharged without a final diagnosis of STEMI were excluded. We identified 703 patients with a confirmed STEMI, including patients with cardiogenic shock and out-of-hospital cardiac arrest. STEMI was defined as the presence of chest discomfort or symptoms of myocardial ischaemia, associated with new or presumed new electrocardiographic abnormalities in the ST-segment (elevation at the J point of at least 0.2mV in leads V1, V2 and V3 and at least 0.1mV in at least two contiguous leads), or new left bundle branch block, associated with elevation of cardiac enzymes at least three times above the upper limit of normal. The Pitié-Salpêtrière University Hospital is part of the Paris STEMI network, which comprises seven PCI centres that are open 24hours/day, 7 days/week. Our centre and the corresponding MICU team cover the south and east part of the city, which represents approximately one-quarter of the Parisian population. We have on-site cardiac surgery available and we are the invasive hub for five non-PCI hospitals, including three emergency departments (EDs) that provide 90% of the interhospital transfer patients.

First medical contact in the urban ST-elevation myocardial infarction network

The FMC can be made through two pathways. The first pathway is MICU contact (field triage); the dispatch centre can be reached by calling the dedicated number for medical emergencies (‘15’). All the calls are operated by a medical regulator who makes the decision to send a fully equipped MICU team on-site, with an on-board emergency doctor who is trained in 18-lead ECG interpretation, decides the reperfusion strategy and administers prehospital treatment. The second pathway is ED contact, where patients are triaged for pPCI after hospital admission (‘walk-ins’), before ambulance transfer to the PCI centre.

Treatment delay definition

A total of seven key-time points were identified and systematically collected: SO or the time of occurrence of the permanent ischaemic symptoms; FMC or time of first physical medical contact with the patient or performance of the first electrocardiogram; activation call or first contact with the on-site pPCI cardiologist; catheterization laboratory door time or time of patient arrival to the catheterization laboratory; intervention time or arterial sheath insertion; time of first balloon inflation; time of thrombolysis in myocardial infarction (TIMI) 3 flow grade.

These time points were used to characterize two important time delays: presentation time (the time delay from SO to FMC); and transfer time (the time delay from FMC to sheath insertion).

Two additional time delays were collected but not used in the analysis: ischaemic time (the time delay from SO to attainment of TIMI 3 flow or the end of PCI [only in patients where TIMI 3 flow was obtained]); and abciximab time (the time delay from FMC to abciximab bolus administration [only in patients treated with abciximab]).

Primary percutaneous coronary intervention procedure

Our catheterization laboratory is open 24hours/day, 7 days/week and can be directly activated by the ED or the MICU. Primary PCI is performed by the on-call senior interventional cardiologist according to contemporary interventional guidelines in STEMI presenters. All patients received at least aspirin and anticoagulation during transfer. The use of glycoprotein IIb/IIIa inhibitors was strongly encouraged for all patients triaged to pPCI and a loading dose of clopidogrel (900mg) was given as soon as possible, according to our local protocol and based on previous studies [9, 10, 11]. Thromboaspiration was used as often as possible if angiographically indicated, followed by systematic stent implantation (unless considered inappropriate by the physician). Subsequent medical treatment included anti-ischaemic, lipid-lowering and antithrombotic drugs, according to current treatment guidelines.

Baseline and procedural data

Baseline data were prospectively collected for all patients and entered in the web-based registry e-Paris. Data regarding medication at admission and during follow-up were recorded, as well as inhospital events until discharge. Our angiographic core laboratory reviewed all angiographic films and blindly evaluated TIMI flow grade, TIMI frame count and TIMI myocardial blush grade. Special attention was given to comorbidities and a risk profile was defined for each patient according to the TIMI risk score for STEMI [12].

Study objectives

Our main objective was to evaluate the impact of transfer time on inhospital death, defined as death from any cause during the initial hospitalization period. Secondary objectives were to evaluate the impact of presentation time on mortality, defining early presenters as patients with an SO – FMC delay120minutes and late presenters as those with an SO – FMC delay>120minutes. We also evaluated the effect of field triage on the different key-time intervals.

Statistical analysis

Continuous variables are presented as means±standard deviations and were compared with Student’s t test. Categorical variables are expressed as rates or proportions and were compared by the Chi2 test or Fisher’s exact test. According to the American College of Cardiology/American Heart Association Task Force on Performance Measures [13], time intervals are expressed as means with interquartile ranges (IQRs; 25th–75th percentiles) and the non-parametric Wilcoxon rank-sum test was adopted for group comparisons (field triage group [MICU] versus non-field triage group [ED]) of time-delay. To address the impact of transfer time on inhospital death we divided the transfer time into quartiles and a multivariable logistic regression model was fit to evaluate the independent variables associated with inhospital mortality with their adjusted effect estimates on inhospital mortality. The following variables (potential confounders) that were associated with inhospital mortality in the univariate analysis were included in the multivariable model: age, creatinine, smoking status, high blood pressure, renal insufficiency, TIMI risk score>4, out-of-hospital cardiac arrest, heart rate, cardiogenic shock, troponin peak, initial TIMI 3 flow, multivessel disease, presentation time group and field triage. All tests were two-sided with a significance level fixed at 5%. We undertook all analyses with SAS software, version 9.0 (SAS Institute Inc., Cary, NC, USA). The study was approved by the local scientific ethical committee (CPP) at the Pitié-Salpêtrière University Hospital.

Patient population and baseline characteristics

Baseline characteristics, treatments and procedural data for the 703 patients included in this study are shown in Table 1, Table 2. Patients were compared according to prehospital triage, i.e. patients who were referred by the MICU (field triage, n =476; 67.7%) with direct transfer from the field to the catheterization laboratory versus those referred by the ED (non-field triage, n =227; 32.3%) with inter- or intrahospital transfer for pPCI. All-comer STEMI patients were recruited with high-risk profiles and frequent comorbidities. Clopidogrel loading dose was administered either in the ED or during transfer by MICU and was600mg in one-third of patients. Clopidogrel loading was completed in all patients to reach a final loading dose of 900mg when discharged from the catheterization laboratory [9, 11]. Abciximab was used in 73.7% of patients and enoxaparin was the most common anticoagulant used. Nine out of 10 patients (88%) underwent pPCI with radial access. MICU patients differed from ED patients with respect to clinical presentation and risk profile; for example, MICU patients displayed a much higher rate of out-of-hospital cardiac arrests (4.9% vs. 1.3%; P =0.017). Angiographic success was similar in both groups but complete ST resolution was higher in the MICU group than in the ED group (71% vs. 64.7%; P =0.027).

Impact of transfer time on inhospital mortality

The inhospital mortality rate was high in the overall study population and did not differ according to prehospital triage (6.0% for the MICU group vs. 5.4% for the ED group; P =0.7). Early presenters demonstrated a trend towards lower inhospital mortality compared with late presenters (4.5% vs. 6.5%; P =0.24). Major independent predictors of inhospital mortality are presented in Table 3 and are mainly related to the severity of both the underlying CAD and the myocardial infarction presentation. The use of enoxaparin (over unfractionated heparin) and the radial approach were independent predictors of better survival.

We performed a sensitivity analysis in the subgroup of patients presenting within 2hours after SO (370 patients), which confirmed the findings of the analysis in the global group, although the model lacked power to demonstrate significant effects of Killip class>2, multivessel disease and enoxaparin treatment.

Unadjusted analysis of the impact of transfer time on mortality showed a clear stepwise increase in inhospital mortality with respect to quartile of transfer time, ranging from 2.99% in the first quartile (Q1) up to 8.65% in the fourth quartile (Q4) (P =0.005) (Table 4). The impact of transfer time on mortality was only present in early presenters (0.96% for Q1 vs. 9.8% for Q4; P =0.006) while no significant relationship was observed in late presenters (7.00% for Q1 vs. 7.8% for Q4; P =0.85) (Figure 1). In the multivariable analysis adjusted for patients’ baseline characteristics, risk factors for mortality and time of presentation, there was no longer an association between transfer time and mortality.

Figure 1

Figure 1. 

Inhospital mortality according to quartiles of transfer time (symptom onset – angiography) (above) and divided according to the group of presentation (below). The early presenters (symptom onset – first medical contact2hours) group is on the left and the late presenters (symptom onset – first medical contact>2hours) group is on the right. ns: not significant.


Impact of field triage by mobile intensive care units on treatment delays

Medians of presentation time and transfer time were shorter in MICU versus ED patients by 55 and 59minutes, respectively (Figure 2). MICU usage was a strong predictor of reduced transfer time (t value 7.75; P <0.0001) in a dedicated multivariable analysis. The time delay from catheterization laboratory door to sheath insertion or first balloon inflation did not differ between MICU and ED patients. Field triage by MICU resulted in a significantly reduced median time to administration of abciximab (by 57minutes) in comparison with ED patients.

Figure 2

Figure 2. 

Median time delay depending on type of first medical contact: mobile intensive care unit (above); emergency department (below). PCI: percutaneous coronary intervention; TIMI: thrombolysis in myocardial infarction.


Median presentation time for the whole study population was 110minutes (IQR, 51–300) and was 57minutes (IQR, 30–90) in early presenters (FMC within 2hours of SO, n =357) versus 324minutes (IQR, 195–693) in-late presenters (FMC>2hours of SO, n =349). Conversely, median transfer time was shorter in early presenters compared with in-late presenters (95minutes [IQR, 76–129] vs. 117minutes [IQR, 85–196]; P <0.0001). The more rapid transfer in early presenters is explained by a higher rate of field triage by MICU in early presenters who seem to call MICU more frequently than late presenters who prefer to ‘walk-in’ to the ED (73.4% vs. 62.9%).


In the present work, we aimed to evaluate the independent effect of transfer time on inhospital mortality of STEMI patients treated with pPCI in a well-organized urban STEMI network using field triage with MICU routinely.

After univariate analysis, we found that a reduction in transfer time for pPCI is associated with improved outcomes, an effect that is only present in early presenters (<2hours of SO) supporting the hypothesis of a threshold effect in time delays (ischaemic time) beyond which rapid treatment does not further improve mortality [14]. However, after adjustment for baseline characteristics, including clinical presentation and time from SO to FMC, there was no longer a relationship between transfer time and hospital mortality, suggesting that individual patient risk and time to presentation are major confounding factors when analysing the impact of reperfusion delay on mortality. Our data supports the idea that factors other than transfer time are key determinants of inhospital mortality, such as the use of enoxaparin rather than unfractionated heparin as the anticoagulation regimen or the use of the radial approach, both of which are independently associated with better outcomes. Finally, we demonstrate that a regional organization based on field triage by MICU with wide coverage of the city and rapid transfer to the catheterization laboratory is very effective for diminishing transfer time in patients presenting with chest pain.

It is only recently that studies have pointed out that mechanical reperfusion strategies should recognize the importance of the presentation time delay [15]. Attention also needs to be given to patient characteristics, as demonstrated in a previous study where door-to-balloon (D2B) time did impact late survival in high-risk and early presenters but not in low-risk patients or late presenters [16]. Although better triage to improve early outcome of STEMI presenters is now established, recent guidelines pay little tribute to patient characteristics and clinical presentation in the process of decision making regarding the best reperfusion strategy [2]. Our results suggest that presentation time and patient baseline characteristics are the most relevant factors impacting early mortality. Indeed, the dramatic reduction in transfer time for pPCI by using MICU to treat earlier and triage patients in the field had no significant impact on inhospital mortality.

Our results do not refute the concept of ‘time is muscle’ but rather reflect the complexity of identifying independent determinants of mortality in STEMI presenters. Not only do they highlight the importance of patient mortality risk in the setting of pPCI, such as patient risk factors, infarct severity [17] and symptom duration [18] – key determinants of early mortality in our series – but they also draw attention to the relative importance of factors other than transfer time. Indeed, in our study, presentation time represents half of the total ischaemic time, itself a major contributor to mortality [19]. Our findings are in accordance with a recent analysis of time delay in randomized trials by Brodie et al., which demonstrated that lowering time to treatment (D2B time in this study) results in improved prognosis in early presenters only [20].

Importantly, when using MICU for field triage, we found that time to treatment could be dramatically reduced, with shorter presentation and transfer times observed. Similar reductions were seen in another recent study [21], reinforcing the need to favour this pathway that facilitates both direct transfer to a pPCI centre and fast administration of antithrombotic therapy, two strategies known to be associated with better outcomes [9, 10, 22, 23, 24]. MICU usage did not appear to impact the prognosis of our study population. These controversial findings may be explained by the fact that the MICU was more frequently the FMC for the sickest patients with a higher rate of out-of-hospital cardiac arrest and cardiogenic shock, and who were unable to ‘walk-in’ to the ED.

Since the launch of the American College of Cardiology’s D2B Alliance and the American Heart Association’s Mission: lifeline programmes, the focus is now on systems improvement of reperfusion in patients with STEMI. With an average median transfer time of 104minutes, our study shows that even in a well-organized urban STEMI network, further efforts can be made to improve transfer time. This delay is mainly driven by long interhospital transfer between ED and PCI centres, as highlighted by a two-fold reduction in transfer time with field triage and direct transfer by MICU. Our data will serve as feedback to all the participants in our STEMI network to highlight the necessity of improvement in our time delays in the setting of pPCI as an exclusive mode of reperfusion; otherwise, thrombolysis may become an option for early presenters with long transfer delays.

We acknowledge several limitations to this study. It represents the results of a single-centre registry with several selection biases, even if our organization network covers a large geographical area. We have considered transfer time (from electrocardiogram to sheath insertion) instead of the D2B time to evaluate the impact of physician-related time on mortality. The D2B time is controversial in our hub organization. Indeed, the concept of ‘hospital door’ is questionable in a prehospital system that bypasses the emergency room. Moreover, the ‘balloon’ time is also questionable as it does not correspond to effective reperfusion (definite TIMI 3 flow) and is biased by long procedures that are rare but associated with delayed reperfusion or procedures without balloon inflation (e.g. thromboaspiration only). Sheath insertion corresponds to the beginning of the angiography and is an unbiased time point. In addition, we did not use ischaemic time in our analysis because a substantial percentage of patients never achieved TIMI 3 flow in this real-life study.

Concerning the observed positive effect of the radial approach on mortality, the femoral approach is predominantly used in the most severe patients in cardiogenic shock and although we adjusted our results on the basis of a multivariable model that included patient’s severity, these results should still be considered with caution. Our data provide the experience of an urban STEMI network using MICU and a single high-volume centre dedicated to radial pPCI. Even if it might reflect current practice in other similar high-volume centres performing expedited care for STEMI patients, we acknowledge that our conclusions may not be fully extrapolated to other centres with a different practice. Nevertheless, two recent trials [25, 26] confirmed our data and demonstrated fewer vascular complications and major cardiovascular and cerebral events with the transradial approach compared with the transfemoral approach in an acute coronary syndrome population.

In conclusion, our present investigation has several major implications. First, it highlights that the association between transfer time and early mortality of STEMI patients treated with pPCI is strongly dependent on baseline characteristics and clinical presentation. Next, it demonstrates that reduction in the total ischaemic time can be achieved by field triage using MICU, allowing fast delivery of appropriate care to the sickest patients. It also emphasizes the need to focus on important prognostic factors other than just transfer time, such as the use of the radial approach – an easy-to-apply technique with a potentially high benefit in bleeding reduction [27] – and the use of enoxaparin, which showed better prognosis over unfractionated heparin in a registry [28] and was confirmed in the randomized ATOLL trial [29].

Finally, the ultimate goal should be a reduction in the overall ischaemic time, that comprises patient-related delays (time to call), presentation time (SO – FMC time) and time to treatment (transfer time or D2B). Such efforts would require a multifaceted approach, involving patient education, global communication from the public health system to the population and appropriate changes in the medical management of STEMI treated with pPCI.

Disclosure of interest

Dr. Silvain has received research grants from sanofi-aventis, Daiichi-Sankyo, Eli Lilly, Brahms, Inserm, Fédération française de cardiologie and Société française de cardiologie; consulting fees from Daiichi-Sankyo, Eli Lilly and The Medicines Company; and speaker honoraria from AstraZeneca, Daiichi Sankyo, Eli Lilly, Iroko Cardio, Servier and Stentys. Prof. Montalescot has received research grants to the institution or consulting/lecture fees from Abbott Vascular, Asante, AstraZeneca, Atrium, Bayer, Biotronik, BMS, Boehringer-Ingelheim, Boston Scientific, Choice Pharma, Brahms, CCS, CHUV, Cordis, Daiichi-Sankyo, Duke Institute, Eli Lilly, Europa, EuroRSCG, Fédération française de cardiologie, Fondation de France, GLG, GSK, HUG, Indegene, Inserm, Institut de France, Iroko, Lead-up, Medtronic, McKinsey, MSD, Nanospheres, Navigant, Novartis, Pfizer, Portola, Roche, Royal College Physicians, sanofi-aventis, Stentys, SGAM, Société française de cardiologie, Springer, Thrombosis Research Institute, The Medicines Company, TIMI group, US Zurich, WebMD and Wolters. Prof. Collet has received research grants from Bristol-Myers Squibb, sanofi-aventis, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Centocor, Fondation de France, Inserm, Fédération française de cardiologie and Société française de cardiologie; consulting fees from sanofi-aventis, Eli Lilly and Bristol-Myers Squibb; and lecture fees from Bristol-Myers Squibb, sanofi-aventis and Eli Lilly. Dr. Beygui has received lecture fees from Roche, sanofi-aventis, Pfizer and Astellas. Dr. O’Connor has received research grants from Menarini and the European Society of Cardiology.


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