Causes of Delay and Associated Mortality in Patients Transferred With

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Timothy D. Henry

Handran, David M. Larson, Steven Mulder, Yale L. Wang, Daniel L. Lips and

Michael D. Miedema, Marc C. Newell, Sue Duval, Ross F. Garberich, Chauncy B.

Elevation Myocardial Infarction

−

ST-Segment

Causes of Delay and Associated Mortality in Patients Transferred With

ISSN: 1524-4539

Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX

doi: 10.1161/CIRCULATIONAHA.111.033118

2011, 124:1636-1644: originally published online September 19, 2011

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Causes of Delay and Associated Mortality in Patients

Transferred With ST-Segment–Elevation Myocardial Infarction

Michael D. Miedema, MD; Marc C. Newell, MD; Sue Duval, PhD; Ross F. Garberich, MS;

Chauncy B. Handran, BS; David M. Larson, MD; Steven Mulder, MD; Yale L. Wang, MD;

Daniel L. Lips, MD; Timothy D. Henry, MD

Background—Regional ST-segment– elevation myocardial infarction systems are being developed to improve timely access to primary percutaneous coronary intervention (PCI). System delays may diminish the mortality benefit achieved with primary PCI in ST-segment– elevation myocardial infarction patients, but the specific reasons for and clinical impact of delays in patients transferred for PCI are unknown.

Methods and Results—This was a prospective, observational study of 2034 patients transferred for primary PCI at a single center as part of a regional ST-segment– elevation myocardial infarction system from March 2003 to December 2009. Despite long-distance transfers, 30.4% of patients (n⫽613) were treated in ⱕ90 minutes and 65.7% (n⫽1324) were treated inⱕ120 minutes. Delays occurred most frequently at the referral hospital (64.0%, n⫽1298), followed by the PCI center (15.7%, n⫽317) and transport (12.6%, n⫽255). For the referral hospital, the most common reasons for delay were awaiting transport (26.4%, n⫽535) and emergency department delays (14.3%, n⫽289). Diagnostic dilemmas (median, 95.5 minutes; 25th and 75th percentiles, 72–127 minutes) and nondiagnostic initial ECGs (81 minutes; 64 –110.5 minutes) led to delays of the greatest magnitude. Delays caused by cardiac arrest and/or cardiogenic shock had the highest in-hospital mortality (30.6%), in contrast with nondiagnostic initial ECGs, which, despite long treatment delays, did not affect mortality (0%). Significant variation in both the magnitude and clinical impact of delays also occurred during the transport and PCI center segments.

Conclusions—Treatment delays occur even in efficient systems for ST-segment– elevation myocardial infarction care. The clinical impact of specific delays in interhospital transfer for PCI varies according to the cause of the delay. (Circulation. 2011;124:1636-1644.)

Key Words:delays _䡲 delivery of health care _䡲 myocardial infarction _䡲 angioplasty, balloon, coronary

T

imely reperfusion is the cornerstone of treatment in patients with ST-segment– elevation myocardial infarction (STEMI). Improving door-to-needle time for fibrinolytic therapy and door-to-balloon time for primary percutaneous coronary intervention (PCI) has been shown to decrease mortality in a linear fashion.1–3_{PCI is the preferred method of reperfusion if it}

can be performed in a timely manner at high-volume centers.4 –7

Yet, only 25% of US hospitals have PCI capability. Both the American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) guidelines currently recommend a door-to-balloon time ofⱕ90 minutes for primary PCI, although the ECS guidelines extend this to⬍120 minutes for transferred patients.5,6

Clinical Perspective on p 1644

The mortality benefit achieved with primary PCI in STEMI patients is diminished by treatment delays.8,9 _{It is therefore}

imperative to develop strategies that both increase access to primary PCI and improve door-to-balloon times.10 –13 _The

ACC launched the D2B Alliance14 _{to improve time to}

treatment in PCI hospitals, and the AHA established Mission: Lifeline15 _{to develop STEMI systems of care that will}

improve timely access to PCI. The Joint Commission in-cludes door-to-balloon times as a core quality assurance measure.16_{Although transfer patients are currently excluded}

from this metric, the ACC/AHA 2008 performance measures recommend that they be included.17

Although randomized trials comparing patients transferred for PCI with onsite fibrinolysis favor PCI, transport and reperfusion times were shorter than what are often achieved in routine practice.18,19_{A recent matched cohort suggests that}

the mortality benefit of PCI over fibrinolysis diminishes as the door-to-balloon time increases and is negated once the

Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. Received November 9, 2009; accepted August 10, 2011.

From the Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN (M.D.M., M.C.N., S.D., R.F.G., C.B.H., D.M.L., S.M., Y.L.W., D.L.L., T.D.H.); University of Minnesota Cardiovascular Disease Division, Minneapolis (M.D.M., T.D.H.); Division of Epidemiology and Community Health, University of Minnesota, Minneapolis (S.D.); and Ridgeview Medical Center, Waconia, MN (D.M.L.).

Correspondence to Timothy D. Henry, MD, Minneapolis Heart Institute Foundation, 920 E 28th St, Ste 100, Minneapolis, MN 55407. E-mail [email protected]

Circulationis available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.111.033118

1636

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door-to-balloon exceeds the door-to-needle time by ⱖ107 minutes.20 _{Regional STEMI treatment systems using}

stan-dardized transfer protocols have been shown to improve treatment times.21–24_{Despite these recent initiatives,}

dispari-ties between guidelines and clinical performance persist. Door-to-balloon times have improved at PCI centers, but fewer than half of STEMI patients undergo PCI within the recommended 90-minute time frame.25_{Time to treatment in}

patients who require interhospital transfer for PCI remains an even greater challenge, with⬍10% of patients treated within 90 minutes and only 15% to 35% treated within 120 minutes.26,27

Despite the increased focus on delays in STEMI care, no published data exist on the reason for delays in an established regional STEMI system. The purpose of this study was to determine the frequency, magnitude, and clinical impact of specific delays in a standardized regional system designed for the rapid transfer of STEMI patients for primary PCI in a real-world population.

Methods

The Minneapolis Heart Institute level 1 MI program is a regional transfer system using a standardized protocol designed to improve time to treatment and clinical outcomes in patients with STEMI presenting to community hospitals without PCI capability. The system design and initial results have previously been published.22,28 Briefly, the diagnosis of STEMI was made by the emergency department physician at the referral hospital, and a single phone call activated the system. Thirty-one hospitals without onsite cardiology consultation participated, including 11 hospitals within 60 miles of the PCI center (designated zone 1) and 20 hospitals (zone 2) between 60 and 210 miles away. Standardized protocols and a predetermined transfer plan (ambulance or helicopter on the basis of locations and availability) were implemented for each site. Transferred patients bypass the PCI center emergency department and proceed directly to the catheterization laboratory.

Patients were enrolled in a comprehensive, prospective database and followed up for 5 years. Inclusion criterion for the prospective registry was STEMI or new left bundle-branch block in patients with chest pain of⬍24 hours’ duration. There were no exclusions; thus, the registry includes patients with out-of-hospital cardiac arrest, cardiogenic shock, elderly patients, and patients with an initially nondiagnostic 12-lead ECG. Each patient’s total door-to-balloon time (arrival at referral hospital to balloon at PCI center) was divided into 3 segments: referral hospital door-in to door-out time, transport time, and PCI center door-to-balloon time.

A 30-30-30 goal was initially established for hospitals in zone 1, setting a target time of 30 minutes at the referral hospital, 30 minutes for transport, and 30 minutes at the PCI center, for a total door-to-balloon time of 90 minutes. It became evident early in the evaluation period that a 30-minute goal was not realistic for the majority of patients at the referral hospitals. This was due largely to delays in time required for ground transport or in waiting for air transport, with an average of a 20-to 25-minute period from contacting air transport 20-to the arrival of the helicopter. Given these unavoidable delays and the ESC guidelines, a 45-45-30 goal was established, with a targeted total door-to-balloon time of 120 minutes for both zones 1 and 2. Detailed time data were recorded for each individual patient. Each patient’s case was independently reviewed with a reason for delay recorded for each segment. If multiple sources of delay occurred within a single segment, the delay of the greatest magnitude was recorded.

Referral hospital door-in to door-out delays (⬎45 minutes) were categorized into 1 of 6 categories: nondiagnostic ECG, diagnostic dilemma, emergency department delay, cardiogenic shock and/or cardiac arrest, awaiting transport, and other. A delay resulting from nondiagnostic ECG was documented if the patient’s initial ECG was nondiagnostic, with a subsequent ECG revealing a STEMI. A delay

resulting from a diagnostic dilemma was coded for a patient with symptoms atypical for STEMI or if the emergency department physician investigated diagnoses other than STEMI, eg, a patient with back pain and ST-segment elevation who required a computed tomography scan to rule out aortic dissection before starting antico-agulation. An emergency department delay was documented if an EKG was not obtained, interpreted, and a call placed to activate the system within 15 minutes of the patient’s arrival without other cause for delay. Delays caused by cardiac arrest and cardiogenic shock were placed in a single category because they frequently coexisted and represented similar high-risk patients. Cardiogenic shock was defined on the basis of definitions in the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial.29_{For both cardiogenic shock and cardiac arrest, the} location of onset was determined (prehospital, referral hospital, transport, PCI center). Delays awaiting transport were documented if

⬎30 minutes elapsed from the time of the call to transport to the patient’s departure from the referral hospital. The other category included patients with delays that did not fit into these definitions.

Transport delays (⬎45 minutes) were divided into 4 categories: weather, distance, traffic, and other. Distance delays were docu-mented if the distance to be covered during transport was too great for the mode of transportation available (⬎40 miles for ground transport and⬎125 miles for air transport).

PCI center door-to-balloon delays (⬎30 minutes) were separated into 5 categories: catheterization laboratory team delay, complex procedure, cardiogenic shock/cardiac arrest in the catheterization laboratory, diagnostic dilemma, and other. A catheterization labora-tory team delay was considered if the PCI procedure did not begin within 15 minutes of the patient’s arrival to the PCI hospital. A complex procedure was identified by reviewing the procedure note and laboratory log and identifying factors such as difficulty achiev-ing vascular access or addressachiev-ing the culprit lesion. Diagnostic dilemma was coded if the cardiologist felt that additional workup was warranted before proceeding with the procedure. For example, this category was selected if a patient with chest pain and subtle ST-elevation but no cardiac risk factors and recent unilateral leg swelling was sent for a computed tomography angiogram to rule out pulmonary emboli before angiography.

Descriptive statistics are displayed as means and SDs for continuous variables; number and percentage with characteristic are given for categorical variables. When continuous variables had skewed distribu-tions (delay times), data are summarized with medians and 25th and 75th percentiles. We used ␹2 or Fisher exact tests to compare in-hospital, 30-day, and 1-year mortality in those with balloon timesⱕ120 minutes and those with times⬎120 minutes. A value ofP⬍0.05 was considered significant, and 95% confidence intervals (CIs) were gener-ated. All statistical calculations and plots were done with Stata 11.1 (College Station, TX). Institutional Review Board approval was ob-tained for data collection, follow-up, and data analysis.

Results

From March 2003 to December 2009, 2034 patients were transferred for PCI, including 1195 patients in zone 1 and 839 patients in zone 2 (Figure 1). At the referring hospital, 6 patients were excluded from the analyses: 5 patients who had unverifiable times and 1 patient who died in the emergency department. Seven patients were excluded from the transport analyses: 6 patients who had unverifiable times and 1 patient who died before transport. In the PCI center analysis, 21 patients were excluded: 3 who had unverifiable delays, 12 who died before the procedure, and 6 who did not undergo angiography. The distributions of total door-to-balloon times are shown in Figure 2A (zone 1) and 2B (zone 2) using the goal of⬍120 minutes as recommended by ESC guidelines. In zone 1, 43% of patients had total door-to-balloon times of ⱕ90 minutes, and 79% were treated in ⱕ120 minutes. In Miedema et al Delays in Patients Transferred for PCI 1637

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zone 2, 12% and 47% were treated inⱕ90 andⱕ120 minutes, respectively. Overall in-hospital, 30-day, and 1-year mortality rates for all patients were 5.4%, 6.1%, and 9.9%, respectively. Compared with patients treated in⬍120 minutes, patients whose total door-to-balloon time was ⬎120 minutes had increased in-hospital mortality (6.4% [95% CI, 4.5– 8.2] versus 4.1% [95% CI, 3.0 –5.1];P⫽0.023) but only a trend at day 30 (6.8% [95% CI, 4.9 – 8.7] versus 4.9% [95% CI 3.7– 6.1];P⫽0.078) and no statistically significant differ-ence at 1 year (10.2%; [95% CI, 7.9 –12.5] versus 8.8% [95% CI 7.2–10.3]; P⫽0.29). The clinical characteristics of the patients treated in ⱕ120 minutes compared with ⬎120 minutes are shown in Table 1. Older patients, diabetics, nonsmokers, and patients with cardiogenic shock were more likely to have delays. A summary of the median times for each delay at the 3 treatment segments is shown in Figure 3.

Referral Hospital Door-in to Door-out Delays The distributions of door-in to door-out treatment times at the referral hospital are shown in Figure 4. The median door-in to door-out time was 54 minutes (25th and 75th percentiles,

40 –74 minutes) and was shorter in zone 1 (48 minutes; 36 – 66 minutes) compared with zone 2 (61 minutes; 48 – 83 minutes). Of the 2028 patients analyzed, 1298 (64.0%) had a delay (door-in to door-out ⬎45 minutes). The frequency, magnitude, in-hospital mortality, and peak creatine kinase-MB for each specific type of delay are shown in Table 2. The most common reasons for delay at the referral hospital were awaiting transport (n⫽535, 26.4% of total patients; 41.2% of delays) and emergency department delay (n⫽289, 14.3% of total patients; 22.3% of delays). The longest delays occurred among patients with diagnostic dilemma (95.5 minutes; 72–127 minutes) and nondiagnostic initial ECG (81 minutes; 64 –110.5 minutes). In-hospital mortality associated with individual delays was highest in patients with cardio-genic shock and/or cardiac arrest (34 of 111, 30.6%) and lowest in patients with initially nondiagnostic ECGs (0 of 181, 0%). Of the 34 patients who died with a delay from cardiogenic shock and/or cardiac arrest, 33 (97.1%) devel-oped the cardiac complication before or within 30 minutes of their arrival to the referral hospital. One of the 2 patients categorized as other suffered from a fear of flying and had to

Figure 1.Flow chart of the number of

patients in the study. PCI indicates percu-taneous coronary intervention; ED, emer-gency department.

Figure 2.Distribution of total door-to-balloon times in zones 1 (A) and 2 (B). Goal door-to-balloon time was 120 minutes (dashed line).

Median balloon time was 94 minutes in zone 1 (solid line) and 123 minutes in zone 2 (solid line). Eighteen patients had

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be reassigned to ground transport; the other patient initially refused transport but later agreed to being transferred. Transport Delays

The distributions of transfer times for patients during the transport segment are shown in Figure 5A and 5B. Overall, 255 patients (12.6%) experienced a delay; 33 patients (2.8%) in zone 1 and 222 patients (26.6%) in zone 2 had transport times ⬎45 minutes. The frequency, magnitude, in-hospital mortality, and peak creatine kinase-MB for each specific type of delay are shown in Table 3. The most common reason for delay in Zone 1 was weather (n⫽23, 1.9% of zone 1 patients; 69.7% of zone 1 transport delays). The longest zone 1 delays

were due to distance (54 minutes; 52–58 minutes). The most common reason for delay in zone 2 was distance (n⫽175, 21.0% of zone 2 patients; 78.8% of zone 2 transport delays). The longest zone 2 delays were due to weather (77 minutes; 63–110 minutes). There were no traffic delays in zone 1 or 2. Mortality for patients with transport delays was similar to that for patients without delays. Delays categorized as other were due to the helicopter being unavailable and helicopter breakdown.

PCI Center Door-to-Balloon Delays

The distribution of door-to-balloon times at the PCI center is shown in Figure 6. Door-to-balloon delays ⬎30 minutes occurred in only 317 patients (15.7%). The frequency, mag-nitude, in-hospital mortality, and peak creatine kinase-MB for each specific type of delay are shown in Table 4. The most common reason for delay included catheterization laboratory team delay (n⫽143, 7.1% of PCI center patients; 45.1% of PCI center delays) and complex procedure (n⫽117, 5.8% of PCI center patients; 36.9% of PCI center delays). The longest delay occurred in patients with diagnostic dilemmas (92.5 minutes; 59 –131 minutes). The highest mortality was seen in patients with cardiogenic shock and/or cardiac arrest (19 of 43, 44.2%). Of the 19 patients who died with a delay resulting from cardiogenic shock and/or cardiac arrest, 13 (68.4%) developed the complication before or within 30 minutes of arrival to the referral hospital, and 3 (15.8%) developed the complication during transport (within 90 minutes from arrival at the referral hospital).

Discussion

This is the first description of the frequency and magnitude of treatment delays in a regional STEMI system of transfer for primary PCI. An understanding of the specific reasons for delay is essential to continued improvement treatment times among transfer patients.

Prolonged door-to-balloon times in STEMI patients under-going PCI are associated with increased mortality,3_especially

in high-risk groups.29_{Data from observational registries have}

Table 1. Baseline Characteristics in Patients With Delays <120 and>120 Minutes Delay ⱕ120 min (n⫽1324) Delay ⬎120 min (n⫽691) P Age, mean (SD), y 61.3 (14.1) 64.0 (14.4) ⬍0.001 Male, % 73.9 70.6 0.12 Hypertension, % 55.1 58.5 0.15 Diabetes mellitus, % 14.4 18.4 0.019 Dyslipidemia, % 54.9 53.9 0.66 Current smoker, % 42.2 36.7 0.018 Family history of coronary artery

disease, %

48.3 47.5 0.72 Prior myocardial infarction, % 18.4 20.0 0.40 Prior percutaneous coronary

intervention, %

19.2 19.1 0.95 Prior coronary artery bypass graft, % 6.0 7.4 0.22 Left bundle-branch block, % 3.4 3.8 0.67 Out-of-hospital cardiac arrest, % 9.2 8.8 0.77 Cardiogenic shock, % 9.6 12.9 0.036

Before PCI 7.3 10.7

After PCI 2.3 2.2

PCI indicates percutaneous coronary intervention.

Figure 3.Median times for individual delays at

each of the 3 treatment segments. PCI indicates percutaneous coronary intervention; ED, emer-gency department.

Miedema et al Delays in Patients Transferred for PCI 1639

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shown that it has been difficult to achieve recommended door-to-balloon times of ⬍90 minutes.25 _{This is especially}

true for STEMI patients who are transferred for PCI. For example, Nallamothu et al26 _{reported times to treatment in}

transferred STEMI patients from the National Registry of Myocardial Infarction and found the national average to be 180 minutes, with more than one quarter of the patients treated in⬎240 minutes. The ACC National Cardiovascular Data Registry data from 2005 and 2006 indicate that only 36.3% of patients were treated in⬍120 minutes.27_{In contrast,}

our results demonstrated that two thirds of patients were treated in⬍120 minutes, and that only 165 patients (8.2%) exceeded total door-to-balloon times of 180 minutes. Al-though these treatment times represent an improvement compared with previously published national averages, de-lays still occurred frequently. Recently published data from Denmark, a small country with an organized transfer system, indicate that 65% of transferred patients still had a system delay (time from emergency medical services contact to primary PCI) of⬎120 minutes.30

The most frequent source of delays occurred at the referral hospital, where just over one quarter of the patients had a delay awaiting transport. The majority of these delays were of low magnitude (median, 14 minutes above goal), and were

associated with a relatively low in-hospital mortality (3.9%). Standardizing transfer protocols, increasing the availability of transport vehicles, and implementing prehospital notification at referral hospitals may lead to earlier dispatching of transport services and improvements in treatment times. Emergency department delays were the second-most-common cause for delay at the referral hospital, and may be improved with continued clinical systems improvement and feedback/quality improvement. Patients with an initially non-diagnostic ECG had the second-longest delays. This delay is best addressed by serial ECGs. Although labeled as having a delay, many of these patients actually had an appropriate time from the diagnostic ECG to balloon inflation. In addition, the lower peak creatine kinase-MB seen in this group suggests that they represent a low-risk patient population in which prolonged treatment times may be less important. In fact, of the 182 patients with delay resulting from an initially nondi-agnostic ECG, there were no in-hospital deaths.

The importance of door-in to door-out time at referral hospitals was recently demonstrated in an analysis of the Acute Coronary Treatment and Intervention Outcomes Net-work (ACTION) Registry–Get With the Guidelines.31 _The

study included ⬎14 000 STEMI patients transferred for primary PCI from 2007 to 2010 and revealed only 11% of

Figure 4.Distribution of door-in to door-out times

at the referral hospital. Goal door-in to door-out time was 45 minutes (dashed line) and median time was 54 minutes (solid line). Twenty-two

patients had door-in to door-out times⬎240

minutes.

Table 2. Frequency, Magnitude, and Mortality Associations of Specific Delays at the Referral Hospital: Referring Hospital Door-in to Door-out Delays

Patients, n (%)

Magnitude (min), Median (25th–75th Percentile) In-Hospital Mortality, % 1-Year Mortality, % Peak CK, Median (25th–75th Percentile), U/L No delay (⬍45 min) 730 (36.0) 35 (28 – 41) 4.0 8.1 846.5 (297–1882) Awaiting transport 535 (26.4) 59 (51–72) 3.9 7.3 710.5 (250–1593.5) ED delay 289 (14.3) 65.5 (56–83.5) 3.8 6.9 853 (274–1559) Nondiagnostic ECG 184 (9.1) 81 (64–110.5) 0 3.3 275 (128–837) Diagnostic dilemma 177 (8.7) 95.5 (72–127) 7.3 12.4 420 (163–934) Cardiac arrest/shock 111 (5.5) 68 (56–86) 30.6 38.7 1381.5 (660–3960) Other 2 (0.1) 60.5 (58–63) Total 2028

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patients in the United States had a door-in to door-out time of ⱕ30 minutes. Patients with a door-in to door-out time of⬎30 minutes had increased mortality compared with those treated inⱕ30 minutes. The median door-in to door-out time in this registry was 68 minutes (43–120 minutes). In comparison, our median door-in to door-out time was shorter (54 minutes; 40 –74 minutes), especially in zone 1 (48 minutes; 36 – 66 minutes), where patients receive primary PCI similar to those studied in the ACTION registry. Our data indicate that not only the delay but also the specific reason for delay and the magnitude affect mortality. Finally, with a median transport time of ⬇25 minutes and a median PCI center time of 20 minutes, the majority of our patients with short referral hospital (door-in to door out) delays were still treated in ⬍120 minutes. This reflects the benefit of a regional STEMI system using standardized protocols and transfer processes.

The transport segment was the least common source of delays. Distance from the PCI center was the most frequent cause of delay, which, for air transfer, will be difficult to improve. The ideal way to improve these times may be to develop a national system of regional STEMI care centers of excellence to limit transfer distances.11,12,32_{Delays resulting}

from distance in patients transferred by ground could poten-tially be improved with greater use of helicopter transport. However, switching to air ambulance transfer for hospitals

within close range of the PCI center should be considered cautiously, especially if ground transport is on site or in close proximity to the referral hospital. Although transfer times may be shortened with air transport, they may be at least partially offset by an extended time at the referring hospital awaiting arrival of air transport, and the cost-effectiveness of ground versus air transport needs to be considered.33 _The

optimal mode of transport for each referral center should be predetermined on the basis of availability of ground and air transport, distance from PCI center, weather, and traffic patterns.

At the PCI center, the majority of patients were treated within the 30-minute goal, reflecting preactivation of the catheterization laboratory team before the patient’s arrival. Catheterization laboratory team delays and complex proce-dures were the most common reasons for delay at the PCI center and were both infrequent and of relatively short magnitude.

The data presented are observational, so drawing conclu-sions about the clinical outcomes associated with individual delays should be done cautiously. However, as would be expected, delay resulting from cardiogenic shock/cardiac arrest was associated with the highest mortality. Current guidelines recommend PCI as the reperfusion method of choice in patients with cardiogenic shock.5,6,34_{In the majority}

Figure 5.Distribution of treatment times during transport in zones 1 (A) and 2 (B). Goal transport time was 45 minutes in zone 1

(dashed line) and in zone 2 (dashed line). Median transport time was 22 minutes in zone 1 (solid line) and 35 minutes in zone 2 (solid line).

Table 3. Frequency, Magnitude, and Mortality Associations of Specific Delays During Transport

Zone 1 Zone 2 Patients, n (%) Magnitude (min), Median (25th–75th Percentile) In-Hospital Mortality, % 1-Year Mortality, % Peak CK, Median (25th–75th Percentile), U/L Patients, n (%) Magnitude (min), Median (25th–75th Percentile) In-Hospital Mortality, % 1-Year Mortality, % Peak CK, Median (25th–75th Percentile), U/L No delay (_⬍45 min) 1160 (97.2) 22 (16 –31) 4.7 8.5 758 (258 –1732) 612 (73.4) 29 (25–37) 6.9 12.1 733 (241–1559) Weather 23 (1.9) 52.5 (50–61) 8.7 13.0 689 (238–3364) 45 (5.4) 77 (63–110) 4.4 8.9 483 (147–1368) Distance 10 (0.8) 54 (52–58) 10.0 10.0 859 (531–1148) 175 (21.0) 55.5 (51–63) 4.0 5.1 578 (223–1650) Traffic . . . . Other . . . 2 (0.2) 61 (53–69) Total 1193 834

CK indicates creatine kinase.

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of these patients, the critical nature of the patients’ condition at presentation led to the delay—intubation, cardiopulmonary resuscitation, multiple shocks, and stabilization. Of the 53 patients in this study who died with a delay caused by cardiogenic shock or cardiac arrest, 46 patients (86.8%) developed the complication before or within 30 minutes of presentation, suggesting that only 7 patients potentially suf-fered the complication as a result of the delay itself.

Only one quarter of the hospitals in the United States have PCI capability; therefore, the development of regional STEMI systems that include the transfer of patients from non-PCI centers is a key strategy to improve timely access to PCI.24_{Although prehospital triage to PCI centers is another}

approach to increase timely access to PCI, only 50% of patients use emergency medical service; therefore, even in metropolitan areas, predetermined arrangements for transfer to a PCI center are important. The Joint Commission uses a door-to-balloon time of 90 minutes as a core measure, but currently transferred patients are excluded. Recently, the ACC/AHA Task Force on Performance Resources recom-mended that door-in/door-out times and first-door-to-PCI times be included.16,17_{The ACC/AHA Task Force}

acknowl-edged that a total door-to-balloon time of 90 minutes for transferred STEMI patients may be difficult to achieve consistently. Although fibrinolytic therapy could be consid-ered for patients who may not achieve targeted treatment

times, many of these patients (including those with cardio-genic shock and cardiac arrest) may have contraindications to fibrinolytics. Healthcare systems may be hesitant to imple-ment transfer for primary PCI in STEMI patients for fear of noncompliance with guidelines and future ramifications in terms of pay for performance.

The ESC guidelines have recently adopted a goal for total door-to-balloon time of 120 minutes for transferred STEMI patients.6_{Our results would support this change and suggest}

that the cause of the delay may be more important than the actual length of delay. More than one third of the deaths from the entire cohort occurred in patients who developed cardio-genic shock and/or cardiac arrest before PCI. The vast majority of patients developed this complication before or shortly after their arrival to the referral hospital, indicating that the cardiac complication led to the delay rather than the delay contributing to the complication. The most recent update of the ACC/AHA guidelines for care of STEMI patients has acknowledged the inability to avoid delays in certain patients, stating “some patients have clinically rele-vant non–system-based delays that do not represent quality-of-care issues.”5

Study Limitations

The study occurred within a single region with an established regional STEMI system and use of a pharmaco-invasive

Figure 6.Distribution of treatment times at the

percutaneous coronary intervention (PCI) center. Goal door-to-balloon time was 30 minutes (dashed line) and median door-to-balloon time was 20 min-utes (solid line). ED indicates emergency

department.

Table 4. Frequency, Magnitude, and Mortality Associations of Specific Delays at the Percutaneous Coronary Intervention Center: Door-to-Balloon Delays

Patients, n (%)

Magnitude (min), Median (25th–75th Percentile) In-Hospital Mortality, % 1 Year Mortality, % Peak CK, Median (25th–75th Percentile), U/L No delay (⬍30 min) 1696 (84.3) 19 (15–23) 3.5 7.3 687.5 (230 –1579) Catheterization laboratory team delay 143 (7.1) 38 (34–50) 5.6 9.1 986 (371–2252) Complex procedure 117 (5.8) 38 (34–45) 8.6 14.5 919 (453–1857) Cardiac arrest/shock 43 (2.1) 41 (35–46) 44.2 55.8 1555 (900–3967) Diagnostic dilemma 14 (0.7) 92.5 (59–131) 7.1 7.1 319 (179–506) Total 2013

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approach for patients transferred long distances (zone 2) and therefore may not be generally applicable to all regions. Although the individual segment delays recorded were arbi-trary, they were based on an attempt to meet current treatment guidelines at the time of the program’s initiation. Finally, the data presented are observational and nonrandomized. Assum-ing a direct cause-and-effect relationship for outcomes and each specific delay should be done cautiously. However, data from prospective registries have distinct advantages, includ-ing analysis of a higher-risk, real-world patient population not included in randomized trials.35,36

Conclusion

The development of a regional STEMI system that includes transfer of patients from non-PCI centers is an important strategy to improve timely access to primary PCI. Our data indicate that clinical outcomes vary significantly according to the reason for the delay, and that not all delays are STEMI system dependent. These results have important implications for the design of regional STEMI systems, the inclusion of transferred STEMI patients in core measures, and potentially the current AHA/ACC guidelines.

Sources of Funding

This research was supported by the Minneapolis Heart Institute Foundation.

Disclosures

None.

References

1. Goldberg RJ, Mooradd M, Gurwitz JH, Rogers WJ, French WJ, Barron HV, Gore JM. Impact of time to treatment with tissue plasminogen activator on morbidity and mortality follow acute myocardial infarction (the Second National Registry of Myocardial Infarction). Am J Cardiol. 1998;82:259 –264.

2. Cannon CP, Gibson CM, Lambrew CT, Shoultz DA, Levy D, French WJ, Gore JM, Weaver WD, Rogers WJ, Tiefenbrunn AJ. Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction.

JAMA. 2000;283:2941–2947.

3. McNamara RL, Wang Y, Herrin J, Curtis JP, Bradley EH, Magid DJ, Peterson ED, Blaney M, Frederick PD, Krumholz HM; NRMI Investi-gators. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction.J Am Coll Cardiol. 2006; 47:2180 –2186.

4. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomized trials.Lancet. 2003;361:13–20.

5. Kushner FG, Hand M, Smith SC Jr, King SB 3rd, Anderson JL, Antman EM, Bailey SR, Bates ER, Blankenship JC, Casey DE Jr, Green LA, Hochman JS, Jacobs AK, Krumholz HM, Morrison DA, Ornato JP, Pearle DL, Peterson ED, Sloan MA, Whitlow PL, Williams DO; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2009 Focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myo-cardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.Circulation. 2009;120:2271–2306.

6. Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M; ESC Committee for Practice Guidelines (CPG), Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Silber S, Aguirre FV, Al-Attar N, Alegria E, Andreotti F, Benzer W, Breithardt O, Danchin N, Di Mario C, Dudek D, Gulba D,

Halvorsen S, Kaufmann P, Kornowski R, Lip GY, Rutten F. Management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology.Eur Heart J. 2008;29: 2909 –2945.

7. Weaver WD, Simes RJ, Betriu A, Grines CL, Zijlstra F, Garcia E, Grinfeld L, Gibbons RJ, Ribeiro EE, DeWood MA, Ribichini F. Com-parison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA. 1997;278:2093–2098.

8. Nallamothu B, Fox KA, Kennelly BM, Van de Werf F, Gore JM, Steg PG, Granger CB, Dabbous OH, Kline-Rogers E, Eagle KA; GRACE Investigators. Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention: the Global Registry of Acute Coronary Events. Heart. 2007;93: 1552–1555.

9. Pinto DS, Kirtane AJ, Nallamothu BK, Murphy SA, Cohen DJ, Laham RJ, Cutlip DE, Bates ER, Frederick PD, Miller DP, Carrozza JP Jr, Antman EM, Cannon CP, Gibson CM. Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reper-fusion strategy.Circulation. 2006;114:2019 –2025.

10. Bradley EH, Herrin J, Wang Y, Barton BA, Webster TR, Mattera JA, Roumanis SA, Curtis JP, Nallamothu BK, Magid DJ, McNamara RL, Parkosewich J, Loeb JM, Krumholz HM. Strategies for reducing the door-to-balloon time in acute myocardial infarction. N Engl J Med. 2006;355:2308 –2320.

11. Jacobs AK, Antman EM, Ellrodt G, Faxon DP, Gregory T, Mensah GA, Moyer P, Ornato J, Peterson ED, Sadwin L, Smith SC; American Heart Association’s Acute Myocardial Infarction Advisory Working Group. Recommendation to develop strategies to increase the number of ST-segment-elevation myocardial infarction patients with timely access to primary percutaneous coronary intervention.Circulation. 2006;113: 2152–2163.

12. Henry TD, Atkins JM, Cunningham MS, Francis GS, Groh WJ, Hong RA, Kern KB, Larson DM, Ohman EM, Ornato JP, Peberdy MA, Rosenberg MJ, Weaver WD. ST-segment elevation myocardial infarc-tion: recommendations on triage of patients to heart attack centers: is it time for a national policy for the treatment of ST-segment elevation myocardial infarction?J Am Coll Cardiol. 2006;47:1339 –1345. 13. Bradley EH, Herrin J, Wang Y, McNamara RL, Radford MJ, Magid DJ,

Canto JG, Blaney M, Krumholz HM. Door-to-drug and door-to-balloon times: where can we improve? Time to reperfusion therapy in patients with ST-segment elevation myocardial infarction (STEMI).Am Heart J. 2006;151:1281–1287.

14. Krumholz HM, Bradley EH, Nallamothu BK, Ting HH, Batchelor WB, Kline-Rogers E, Stern AF, Byrd JR, Brush JE Jr. A campaign to improve the timeliness of primary percutaneous coronary intervention.JACC Cardiovasc Interv. 2008;1:97–104.

15. Mission: Lifeline: a new plan to decrease deaths from major heart blockage. http://www.americanheart.org/presenter.jhtml?identifier⫽ 3048034. Accessed August 1, 2011.

16. Current specification manual for national hospital quality measures. http://www.jointcommission.org/PerformanceMeasurement/Performance Measurement/Current⫹NHQM⫹Manual.htm. Accessed August 1, 2011. 17. Krumholz HM, Anderson JL, Bachelder BL, Fesmire FM, Fihn SD, Foody JM, Ho PM, Kosiborod MN, Masoudi FA, Nallamothu BK; American College of Cardiology/American Heart Association Task Force on Performance Measures; American Academy of Family Physicians; American College of Emergency Physicians; American Association of Cardiovascular and Pulmonary Rehabilitation; Society for Cardiovascular Angiography and Interventions; Society of Hospital Medicine. ACC/AHA 2008 performance measures for adults with ST-elevation and non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Performance Measures for ST-Elevation and Non-ST-Elevation Myocardial Infarction): developed in collaboration with the American Academy of Family Physicians and the American College of Emergency Physicians: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, Society for Cardiovascular Angiography and Interventions, and Society of Hospital Medicine.Circulation. 2008;118:2596 –2648.

18. Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, Abildgaard U, Pedersen F, Madsen JK, Grande P, Villadsen AB, Krusell LR, Haghfelt T, Lomholt P, Husted SE, Vigholt E, Kjaergard HK, Mortensen LS; DANAMI-2 Investigators. A comparison of coronary

(10)

angioplasty with fibrinolytic therapy in acute myocardial infarction.

N Engl J Med. 2003;349:733–742.

19. Widimsky´ P, Budesıńsky´ T, Vorać D, Groch L, Zelı´zko M, Aschermann M, Branny M, St’a´sek J, Formańek P; PRAGUE Study Group Investi-gators. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction: final results of the ran-domized national multicentre trial: PRAGUE-2.Eur Heart J. 2003;24: 94 –104.

20. Pinto DS, Kirtane AJ, Frederick PD, Dejam A, Miller DP, Henry TD, Gibson CM. The benefit of transferring STEMI patients for PCI compared with administration of onsite fibrinolytic declines as delays increase.Circulation.2010;122:A13146.

21. Jollis JG, Roettig ML, Aluko AO, Anstrom KJ, Applegate RJ, Babb JD, Berger PB, Bohle DJ, Fletcher SM, Garvey JL, Hathaway WR, Hoekstra JW, Kelly RV, Maddox WT Jr, Shiber JR, Valeri FS, Watling BA, Wilson BH, Granger CB; Reperfusion of Acute Myocardial Infarction in North Carolina Emergency Departments (RACE) Investigators. Imple-mentation of a statewide system for coronary reperfusion for ST-elevation myocardial infarction.JAMA. 2007;298:2371–2380.

22. Henry TD, Sharkey SW, Burke MN, Chavez IJ, Graham KJ, Henry CR, Lips DL, Madison JD, Menssen KM, Mooney MR, Newell MC, Pedersen WR, Poulose AK, Traverse JH, Unger BT, Wang YL, Larson DM. A regional system to provide timely access to percutaneous coronary inter-vention for ST-elevation myocardial infarction. Circulation. 2007;116: 721–728.

23. Aguirre FV, Varghese JJ, Kelley MP, Lam W, Lucore CL, Gill JB, Page L, Turner L, Davis C, Mikell FL; Stat Heart Investigators. Rural interhospital transfer of ST-elevation myocardial infarction patients for percutaneous coronary revascularization: the Stat Heart Program.

Circulation. 2008;177:1145–1152.

24. Henry TD, Gibson CM, Pinto DS. Moving toward improved care for the patient with ST-elevation myocardial infarction: a mandate for systems of care.Circ Cardiovasc Qual Outcomes. 2010;3:441– 443.

25. Eagle KA, Nallamothu BK, Mehta RH, Granger CB, Steg PG, Van de Werf F, Lo´pez-Sendo´ n J, Goodman SG, Quill A, Fox KA; Global Registry of Acute Coronary Events (GRACE) Investigators. Trends in acute reperfusion therapy for ST-segment elevation myocardial infarction from 1999 to 2006: we are getting better but we have got a long way to go.Eur Heart J. 2008;29:609 – 617.

26. Nallamothu BK, Bates ER, Herrin J, Wang Y, Bradley EH, Krumholz HM; NRMI Investigators. Times to treatment in transfer patients undergoing primary percutaneous coronary intervention in the United States: National Registry of Myocardial Infarction (NRMI)-3/4 analysis.

Circulation. 2005;111:761–767.

27. Chakrabarti A, Krumholz HM, Wang Y, Rumsfeld JS, Nallamothu BK; National Cardiovascular Data Registry. Time-to-reperfusion in patients undergoing interhospital transfer for primary percutaneous coronary intervention in the U.S: an analysis of 2005 and 2006 data from the National Cardiovascular Data Registry. J Am Coll Cardiol. 2008;51: 2442–2443.

28. Henry TD, Unger BT, Sharkey SW, Lips DL, Pedersen WR, Madison JD, Mooney MR, Flygenring BP, Larson DM. Design of a standardized system for transfer of patients with ST-elevation myocardial infarction for percutaneous coronary intervention.Am Heart J. 2005;150:373–384. 29. Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley JD,

Buller CE, Jacobs AK, Slater JN, Col J, McKinlay SM, LeJemtel TH. Early revascularization in acute myocardial infarction complicated by cardiogenic shock: SHOCK Investigators: Should We Emergently Revas-cularize Occluded Coronaries for Cardiogenic Shock.N Engl J Med. 1999;341:625– 634.

30. Turkelson CJ, Sorenson JT, Maeng M, Jenson LO, Tilsted HH, Trautner S, Vach W, Johnsen SP, Thuesen L, Lassen JF. System delay and mortality among patients with STEMI treated with primary percutaneous coronary intervention.JAMA. 2010;304:763–761.

31. Wang TY, Nallamothu BK, Krumholz HM, Li S, Roe MT, Jollis JG, Jacobs AK, Holmes DR, Peterson ED, Ting HH. Association of door-in to door-out time with reperfusion delays and outcomes among patients transferred for primary percutaneous coronary intervention.JAMA. 2011; 305:2540 –2547.

32. Granger CB, Henry TD, Bates WE, Cercek B, Weaver WD, Williams DO. Development of systems of care for ST-elevation myocardial infarction patients: the primary percutaneous coronary intervention (ST-elevation myocardial infarction-receiving) hospital perspective.

Circulation. 2007;116:e55– e59.

33. McMullan JT, Hinckley W, Bentley J, Davis T, Fermann GJ, Gunderman M, Hart KW, Knight WA, Lindsell CJ, Shackleford A, Gibler WB. Reperfusion is delayed beyond guideline recommendations in patients requiring interhospital helicopter transfer for treatment of ST-segment elevation myocardial infarction.Ann Emerg Med. 2011;57:213–220. 34. Brodie BR, Stone GW, Cox DA, Stuckey TD, Turco M, Tcheng JE,

Berger P, Mehran R, McLaughlin M, Costantini C, Lansky AJ, Grines CL. Impact of treatment delays on outcomes of primary percutaneous coronary intervention for acute myocardial infarction: analysis from the CADILLAC trial.Am Heart J. 2006;151:1231–1238.

35. Steg PG, Lo´pez-Sendo´ n J, Lopez de Sa E, Goodman SG, Gore JM, Anderson FA Jr, Himbert D, Allegrone J, Van de Werf F; GRACE Investigators. External validity of clinical trials in acute myocardial infarction.Arch Intern Med. 2007;167:68 –73.

36. Bhatt DL. Advancing the care of cardiac patients using registry data: going where randomized clinical trials dare not.JAMA. 2010;303:2188 –2189.

CLINICAL PERSPECTIVE

Regional ST-segment– elevation myocardial infarction systems are being developed to improve timely access to primary percutaneous coronary intervention (PCI). System delays may diminish the mortality benefit achieved with primary PCI in ST-segment– elevation myocardial infarction patients, but the specific reasons for and clinical impact of delays in patients transferred for PCI are unknown. We report the frequency, magnitude, and clinical impact of specific delays that occur at the referral hospital, during transport, and at the PCI hospital for 2034 patients transferred for PCI in a regional ST-segment– elevation myocardial infarction system. Despite the use of evidence-based strategies to improve treatment times, delays still occurred frequently within the ST-segment– elevation myocardial infarction system. Delays occurred most frequently at the referral hospital, and were most often due to awaiting transport and emergency department delays. Delays occurred less frequently during transport or at the PCI center. Diagnostic dilemmas and nondiagnostic initial ECGs led to delays of the greatest magnitude but had limited or no impact on mortality. Delays caused by out-of-hospital cardiac arrest and/or cardiogenic shock had the highest impact on in-hospital mortality. In these high-risk patients, the delay rarely led to the cardiac arrest or cardiogenic shock; instead, the critical nature of the patient’s illness resulted in the delay. These results have implications for the design of regional ST-segment– elevation myocardial infarction systems and may affect the current American College of Cardiology/American Heart Association guidelines for time to treatment in transferred patients.