Process and outcome evaluation of a regional pulmonary embolism response team

Abstract

AbstractSection Background

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Most pulmonary embolism response team (PERT) reports are limited to single hospitals. We evaluated whether process and clinical outcomes differed for patients presenting to pulmonary embolism (PE) referral versus non-referral centers within a regional PERT program. We also compared outcomes among the three PE referral centers.

AbstractSection Methods

We retrospectively analyzed registry data from adult patients treated by a PERT with centralized consultation and transfer protocols across 20 emergency departments (EDs) in North Carolina (2017–2024). Process and clinical outcomes were compared between centers using chi-square tests and t-tests. We identified temporal trends in the aggregate data.

AbstractSection Results

Of 2119 patients, 1173 and 946 had ED PERT activations at referral centers and non-referral centers, respectively. Of non-referral center activations, 534 (56.4%) were transferred to a referral center. Times were longer for patients who presented to referral centers vs. non-referral centers for some process outcomes (e.g., time to first heparin), but shorter for others (e.g., time to catheter-directed thrombolysis [CDT]). We found no significant differences between referral and non-referral centers in advanced intervention use (22.1% vs. 21.9%, p = 0.92), clinical deterioration (14.6% vs. 14.6%, p = 1.00), or major bleeding (9.1% vs. 7.0%, p = 0.08). However, PE severity and clinical deterioration (CD) varied significantly between referral centers (15.0% vs. 17.8% vs. 10.5%, p = 0.008), while advanced intervention use (22.0% vs. 21.2% vs. 23.2%, p = 0.76) and major bleeding (9.8% vs. 10.3% vs. 7.3%, p = 0.28) did not. CD and major bleeding changed significantly over time (p < 0.008); CDT and mechanical thrombectomy (MT) increased nonlinearly (p < 0.001); and systemic thrombolysis (ST) remained stable. Times to MT and ST decreased over time (p < 0.02). There was no change in timing for heparin or CDT (p > 0.3).

AbstractSection Conclusions

In our regional PERT with centralized consultation and transfer protocols, process and clinical outcomes were similar between referral and non-referral centers. There were significant differences in PE severity and CD between referral centers, but advanced intervention use and major bleeding were similar. We identified temporal trends, reflecting expanded availability of interventional therapies and our PERT evolution.

Background

Pulmonary embolism (PE) is a complex cardiovascular emergency that can be difficult to diagnose and manage. Patients with PE and right ventricular dysfunction (RVD) are at increased risk of clinical deterioration. While many improve with anticoagulation alone, some require advanced interventions. Multidisciplinary pulmonary embolism response teams (PERTs) were established to prevent deterioration through rapid assessment and coordinated care [1,2,3]. Their goal is to improve outcomes by streamlining decision-making, transfers, and timely interventions [2,3,4].

Published evaluations of PERTs are limited. Most studies compare treatments and outcomes within a few years pre- and post-PERT implementation at single hospitals [2, 5,6,7,8,9]. Few multi-center studies exist, and generalizability is limited by differences in hospital practices, physician preferences, and available resources. Even within the same health system, care may differ based on the hospital of initial presentation. Some hospitals serve as PE referral centers, with multidisciplinary staffing and advanced intervention options not available at other sites.

Evaluation of PERT performance is also hindered by a lack of standardized process measures. While benchmarks exist for acute conditions like stroke or myocardial infarction, PE lacks similar metrics. As a result, the effects of PERTs on clinical decision-making, efficiency, and outcomes across hospitals remain unclear.

Our primary objective was to compare process outcomes and clinical outcomes between patients presenting to PE referral vs. non-referral centers within a regional PERT program. Secondarily, we evaluated differences among the three referral centers. As an exploratory objective, we assessed trends in process outcomes and clinical outcomes over the eight years since program launch. Throughout this manuscript, we refer to our system’s PERT as “CODE PE team.”

Methods

Study design and setting

We conducted a retrospective analysis of eight years of data from the Clinical Outcomes in Pulmonary Embolism Research Registry (COPERR), an observational registry of adult patients treated by the CODE PE team across 20 emergency departments (EDs) within the Atrium Health system in North Carolina, USA. The registry and related reports were approved by the local institutional review board. We examined patient characteristics, process outcomes, and clinical outcomes. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines [10]. The only use of large language models (i.e., ChatGPT, Microsoft 365 Copilot) was to paraphrase our original content to provide more succinct explanations of a few concepts or to organize tables.

Three Atrium Health hospitals (Hospitals A, B, and C) serve as PE referral centers based on their 24/7 availability of catheter-directed intervention (CDI), dedicated CODE PE teams, in-house critical care services equipped to manage high-acuity cases, and ability to accept transfers at any time. All three can initiate extracorporeal membrane oxygenation (ECMO) cannulation, but ongoing ECMO management requires transfer to Hospital B, the academic center. Non-referral centers are Atrium Health EDs not located within Hospital A, B or C. One non-referral center (Atrium Health University City) had partial CDI support from vascular surgery and interventional radiology between 2017 and March 2023. After that, patients with massive or severe submassive PE were redirected to the referral centers for advanced care.

Study population

We included all adults (> 18 years) with confirmed PE for whom CODE PE was activated in the ED between January 2017 and August 2024. All had evidence of right ventricular (RV) strain, defined by an RV to left ventricle ratio (RV: LV) ≥ 1.0 on computed tomography pulmonary angiography (CTPA) or signs of RVD on echocardiography (point-of-care or formal). We defined PE severity by a hybrid of classifications used by the PERT Consortium, American Heart Association, and the European Society of Cardiology [11,12,13,14]. Patients with RVD and sustained hypotension (systolic blood pressure < 90 mmHg for 15 or more minutes), vasopressor use, or cardiac arrest were classified as massive PE. Those with RVD but without criteria for massive PE classification were classified as submassive PE, and we segmented this group into severe submassive PE and non-severe submassive PE as follows: 1) Those with RVD and episodic hypotension (systolic blood pressure < 90 mmHg for less than 15 min), shock index > 1.0, respiratory distress, syncope/presyncope, or clot-in-transit were classified as severe submassive PE. Patients without massive or severe submassive features were considered non-severe submassive PE. Our CODE PE program has distinguished subgroups of submassive PE since March 2020. For CODE PE activations with submassive PE prior to March 2020, we retrospectively assigned the appropriate subgroup (severe submassive vs. non-severe submassive PE). In March 2023, an internal retrospective review of COPERR data by a multidisciplinary committee found patients who met the severe submassive PE definition above were more likely to deteriorate from submassive to massive PE or need rescue intervention. This classification has since informed real-time triage within our system [15, 16]. We excluded patients diagnosed with PE during hospitalization as these cases are not entered into COPERR.

CODE PE team composition

Our multidisciplinary CODE PE team includes the ED physician and an interventional specialist—either from interventional cardiology, interventional radiology, or vascular surgery—depending on available resources at each site. In more complex cases, cardiothoracic surgeons and ECMO specialists may also be involved. Vascular medicine physicians contribute to post-acute care, including follow-up planning and long-term anticoagulation management. At non-referral centers, the team is supported by a virtual critical care physician (VCC), a board-certified intensivist available 24/7 from a centralized location. The VCC verifies PE severity status and determines if the patient needs to be transferred to a referral center and, if so, with what level of urgency. Initial decisions on CODE PE activations are made jointly by the VCC and the initiating ED physician, with additional specialists consulted in real time as needed.

Atrium Health ED physicians and CODE PE team members receive CODE PE committee-led education, which is supported by CODE PE risk stratification algorithm posters, standardized order sets and power plans within the electronic medical record (EMR), rigorous data capture, and regular quality improvement reporting to the CODE PE committee.

CODE PE activation

As illustrated in Fig. 1, CODE PE activation requires confirmation of PE on CTPA along with evidence of RVD, defined as either elevated troponin or an RV size greater than the LV on imaging (CTPA, comprehensive transthoracic echocardiography [TTE], or point-of-care ultrasound). [Trained ED physicians performed point-of-care echocardiographic visual assessments for RVD [17, 18]. Sonographers performed comprehensive echocardiographic assessments and measurements.] Elevated troponin was defined using i-STAT cardiac troponin I or T > 0.07 ng/mL or high-sensitivity troponin levels exceeding 12 ng/L for females or 20 ng/L for males. TTE reporting included focused assessments of RV dimensions, systolic function, pressure, and cardiac output. Other CODE PE guidelines were internally decided. For example, when restarting heparin after systemic thrombolysis administration, we used a cut-off of 110 s to signal approach into the therapeutic range (60–100 s) and restart of heparin.

Fig. 1

CODE PE pathway in use March 2023 to present

When an ED provider in a referral center activates CODE PE, a secure in-house chat system simultaneously notifies all relevant CODE PE team members. When an ED provider in a non-referral center activates CODE PE, in-house multidisciplinary expertise is not immediately available, so the secure chat only notifies the VCC. The VCC then coordinates rapid triage, verifies PE severity, consults with specialists, and facilitates transfers for patients needing advanced care.

As shown in Fig. 2, CODE PE activations between January 2017 and March 2023 included patients with massive, severe submassive, and non-severe submassive PE. In March 2023, the activation criteria were revised as part of a quality improvement initiative to exclude non-severe submassive PE since these patients rarely required escalation or intervention and were effectively managed by primary teams. This change, described previously, improved clarity and consistency across the health system.

Fig. 2

CODE PE pathway in use January 2017 to March 2023

Data collection

Trained data extractors reviewed each patient’s EMR for demographics, PE risk factors, comorbidities (including the Charlson Comorbidity Index [19]), clinical presentation, process outcomes, and clinical outcomes (in-hospital and 30-day post-diagnosis). For time-based measures, time-stamps were abstracted from the EMR for radiologist signature on computed tomography interpretation, medications, and procedures. All data were entered into the COPERR database using Research Electronic Data Capture (REDCap) hosted at Atrium Health [20].

Outcome measures

Process outcomes

We evaluated process-related aspects of CODE PE activations, focusing on time intervals, use of advanced PE interventions, and interhospital transfers. We measured times from PE diagnosis (when radiologist signed computed tomography interpretation) to CODE PE activation and from CODE PE activation to initiation of first heparin dose (unfractionated or low molecular weight). For advanced PE intervention, we reported usage of each type of advanced intervention as well as the time from CODE PE activation to intervention. Advanced PE interventions were defined as systemic thrombolysis (including alteplase 100 mg or 50 mg over 2 h or off-label use of tenecteplase 40–50 mg bolus) and CDI (including ultrasound-assisted catheter-directed thrombolysis [CDT], large and small bore catheter-based embolectomy, and mechanical thrombectomy using devices like AngioVac (AngioDynamics, Latham, NY), Indigo (Penumbra, Alameda, CA), or FlowTriever (Inari Medical, Irvine, CA). We also reported usage of ECMO and surgical embolectomy. Other process outcomes included presence or absence of interhospital transfer, intensive care unit (ICU) admission, ICU length of stay (LOS), and total hospital LOS. For transferred patients, we recorded time from CODE PE activation to discharge from the referring hospital, and time to arrival and admission at the receiving center.

Clinical outcomes

Clinical outcomes included PE-related clinical deterioration and major bleeding during the index hospitalization. Clinical deterioration was defined as cardiac arrest, use of inotropes or vasopressors for symptomatic hypotension (e.g., dobutamine, norepinephrine, dopamine, vasopressin, epinephrine), emergent respiratory interventions, or PE-related death. Respiratory interventions included mechanical ventilation, positive pressure ventilation, or escalation to high-flow oxygen, excluding routine or chronic ventilatory support. Cause of death was based on physician documentation when available; if no alternative cause was listed, death was considered PE-related. For patients presenting with massive PE, continued hemodynamic instability into or during admission was also classified as clinical deterioration. Major bleeding was defined according to the International Society on Thrombosis and Hemostasis criteria [21].

Statistical analysis

Sample size was based on all patients in the COPERR database with complete data. We calculated counts, percentages, means, and standard deviations for descriptive statistics and reported missing data per variable. Statistical comparisons were made using bivariate analyses: Student’s t tests for continuous variables, and chi-square or Fisher’s exact tests for categorical variables, grouped by whether patients presented to a PE referral or non-referral center (primary dependent variable). For comparisons among the three referral centers (secondary dependent variable), we used ANOVA for continuous and chi-square or Fisher’s exact tests for categorical variables. Analyses were conducted in R and RStudio [22, 23]. A two-tailed p value < 0.05 was considered significant.

For the primary objective, patients were stratified by whether they presented and were diagnosed with PE at a referral center ED or a non-referral center ED. We conducted a subgroup analysis of CODE PE activations at non-referral centers, comparing outcomes between patients who were transferred to a PE referral center vs. those who were not. For the secondary objective, only patients who presented to and were diagnosed at one of the referral centers (Hospitals A, B, or C) were included.

For the exploratory objective, we grouped patients by the date of CODE PE activation into 6-month intervals over the 8-year study period and assessed temporal trends in key variables.

We used a combination of descriptive statistics, visualizations, and inferential models to identify temporal trends. This comprehensive analytic approach was designed to provide insights into how variables changed over time and to identify significant shifts in our data. The descriptive and exploratory analysis involved displaying continuous measurements (e.g., times to treatment) and categorical proportions (e.g., PE severity, advanced intervention use, clinical deterioration, major bleeding) over time.

We used regression to account for the randomness/variability in our raw data to smooth or average out trends and displayed both sets of data. A generalized additive model with normally distributed residuals and a penalized spline was used to model trends over 6-month intervals for each outcome [23]. Predictions were generated on the logit scale and converted to probabilities with 95% confidence intervals using the delta method. Model fit was summarized using estimated degrees of freedom (representing the complexity of the smoothed trend line) and chi-square tests and p-values (representing significant change over time). Degrees of freedom at or close to 1.0 represent linearity. P values less than 0.05 represent significant changes over time. Predicted probability and mean time curves with 95% confidence intervals were plotted to visualize smoothed or averaged changes over time.

Results

Primary objective

Patient characteristics

As shown in Table 1, the mean age of the cohort was 62.2 years (SD 16.8); 51.2% were female, 61.3% White, and 34.5% Black. Of 2119 PE patients with ED-initiated CODE PE activations, 1173 (55.2%) presented to referral centers and 946 (44.8%) to non-referral centers (Fig. 3). Demographics were similar between groups, except for age: patients at referral centers were older (63.1 vs. 61.2 years; p = 0.009). PE severity (massive vs. submassive) was similar across sites, but high bleeding risk was more common at referral centers (17.1% vs. 11.1%; p < 0.001).

Table 1 Characteristics of patients for whom CODE PE was activated at PE referral centers vs. non-referral centers

Fig. 3

Study flow diagram

Process outcomes

Table 2 shows the mean time from PE diagnosis to CODE PE activation was shorter at referral centers (0.6 vs. 3.0 h), but not statistically significant (p = 0.25). However, time from activation to first heparin was longer at referral centers (1.9 vs. 0.9 h; p < 0.001). Mean times from CODE PE activation to the start of systemic thrombolysis were similar at referral and non-referral centers (11.1 vs. 13.8 h; p = 0.20). Times to CDT and mechanical thrombectomy were slightly shorter (not statistically significant) at referral centers than non-referral centers.

For first heparin administration, Table 2 shows unfractionated heparin was used more often than low molecular weight heparin at all centers, with PE referral centers using unfractionated heparin slightly more than non-referral centers (65.3% and 60.8%, respectively). The difference in choice of first heparin (unfractionated vs. low molecular weight heparin) between referral and non-referral centers had borderline significance (p = 0.05). Use of advanced interventions did not vary significantly between referral and non-referral centers. Most CDIs performed were CDT and mechanical thrombectomy.

While patients were rarely transferred (2.6%) from referral centers, 56.4% of CODE PE activations at non-referral centers were transferred to a referral center. ICU admission was more frequent at non-referral centers than referral centers (58.5% vs. 49.4%; p < 0.001), but ICU LOS was similar (2.4 days). Mean hospital LOS was not significantly different (6.2 vs. 5.3 days; p = 0.08).

Table 2 Process outcomes for CODE PE activations at PE referral vs. non-referral centers

Clinical outcomes

No significant differences were found in PE-related clinical deterioration or major bleeding between referral and non-referral centers (Table 3). Thirty-day outcomes were also similar.

Table 3 shows 125 patients experienced cardiac arrest either during ED presentation or during index PE hospitalization (this includes the 74 patients shown in Tables 1 and 33 of whom survived to hospital discharge [data not shown]). Seventy patients had cardiac arrest both at ED presentation and during index PE hospitalization; 55 patients without cardiac arrest at ED presentation had subsequent cardiac arrest during hospitalization. Of the 55, 10 were transferred to one of the PE referral centers, none of whom experienced cardiac arrest en route to the referral center.

Table 3 Clinical outcomes for CODE PE activations at PE referral vs. non-referral centers

Subgroup analysis results

Table 4 shows significantly more patients were transferred from non-referral centers with severe submassive PE (272 [50.9%] vs. 175 [42.5%]) and massive PE (47 [8.8%] vs. 21 [5.1%]) compared with those not transferred (p < 0.001). A smaller proportion of Black patients were transferred compared to White patients. Transferred patients were discharged from non-referral centers 5.5 h after CODE PE activation, arrived at a referral center within 1.1 h, and were admitted 6.6 h after initial CODE PE activation. Times from diagnosis to CODE PE activation and to first anticoagulation did not differ by transfer status. Times to advanced interventions, which were used more frequently among transferred patients compared with non-transfers (30.3% and 13.8%, respectively; p < 0.001), were longer for those transferred than those not transferred as shown in Table 4 for systemic thrombolysis (16.2 vs. 7.0 h, p = 0.008) and CDT (25.8 vs. 9.2 h, p = 0.003). A small proportion (6.6%) of non-transferred patients received CDT, all at the one non-referral site that provided CDT prior to March 2023 (Atrium Health University City), with a mean time from CODE PE activation to CDT of 9.2 h. Transferred patients had higher ICU admission rates (67.2% vs. 47.1%; p < 0.001), but no significant differences in clinical outcomes (in-hospital or 30-day).

Table 4 Comparison of patients who were and were not transferred to a PE referral center from non-referral centers*

Secondary objective

Patient characteristics

As shown in Table 5, significant differences were observed between referral centers. Hospital B (academic) had a higher proportion of Black patients, while patients at Hospital A were older. Hospital B also treated more patients with massive PE (11.3%) compared to Hospitals A (8.4%) and C (5.4%) (p = 0.03).

Table 5 Comparison of patient characteristics, process outcomes, and clinical outcomes between three PE referral centers*

Process outcomes

Time from PE diagnosis to CODE PE activation was similar across referral centers (0.8, 0.7, and 0.5 h, respectively; p = 0.44), as was time to first heparin. Time to systemic thrombolysis did not differ between referral centers, but time to CDT did (9.8, 33.3, and 18.2 h, respectively; p = 0.007). Times to other CDIs were similar. Use of advanced interventions was comparable (21–23%; p = 0.76), but systemic thrombolysis was used more frequently at Hospital B (13.8%) than at Hospitals A and C (7.0% and 6.6%, respectively; p < 0.001). Conversely, CDIs were performed more often at Hospitals A and C than at Hospital B (12.5% and 13.7%, respectively, vs. 3.4%; p < 0.001). Surgical embolectomy was only performed at Hospital B.

ICU admission was lower at Hospital A (39.7%) than at Hospitals B and C (53.7% and 51.3%, respectively; p < 0.001). ICU LOS was shortest at Hospital C (1.9 vs. 2.8 and 2.6 days; p < 0.001). Hospital C also had the shortest overall LOS (4.6 vs. 7.8 and 6.5 days, respectively; p = 0.008).

Clinical outcomes

Table 5 shows clinical deterioration differed significantly between referral centers (Hospital B highest at 17.8%, including 9.4% mortality; p = 0.008). Cardiac arrest and vasopressor use were also highest at Hospital B. No significant differences were seen in in-hospital major bleeding or 30-day outcomes.

Exploratory objective

Figure 4 illustrates trends in PE severity over 6-month intervals from 2017 to 2024. A sharp decline in non-severe submassive PE activations occurred in early 2023 following the revision in our CODE PE activation criteria.

Fig. 4

Predicted probability of each PE severity class over time

Table 6 shows the number of CODE PE activations in each 6-month interval. Both Table 6; Fig. 5 show average times between CODE PE activation and start of first heparin and advanced interventions. Over the 8-year period, time to first heparin administration remained relatively prompt and stable, typically occurring within 1 to 2 h of CODE PE activation. In contrast, times to start of advanced interventions were more variable. Time to mechanical thrombectomy was often prolonged before 2020, with average times exceeding 70 h in some 6-month periods; however, much shorter times were observed starting in late 2021. Average time to CDT fluctuated, ranging from 14 to 44 h, with the highest delays observed in early 2023 (43.7 h). More recent intervals suggest modest improvements. Systemic thrombolysis, in contrast, demonstrated a clear trend toward faster administration over time. Mean times decreased from approximately 15–17 h in the earlier years to less than 5 h in 2024, with the shortest interval recorded in late 2023 (2.5 hours).

Table 6 Average times between CODE PE activation and start of advanced intervention over time

Fig. 5

Average time to start of treatment over time*. * CDT denotes catheter-directed thrombolysis

Figure 6 shows the smoothed trend lines. The EDFs for average times from CODE PE activation to start of intervention shown in Table 7 were all close to 1.0 indicating linearity. The p-values, however, show mechanical thrombectomy and systemic thrombolysis had significant change over time (p = 0.024 and p = 0.014, respectively). In contrast, time to first heparin (p = 0.51) and CDT (p = 0.32) demonstrated no significant changes in timing and remained linearly stable over the study period.

Fig. 6

Predicted time to start of treatment over time*. *CDT denotes catheter-directed thrombolysis

Table 7 Temporal trends for times to start of treatment

Table 8 and Fig. 7 show the raw proportions of patients who received an advanced intervention (reported in aggregate and by type of intervention), experienced clinical deterioration, and had major bleeding for each 6-month interval. The proportion of CODE PE activations with advanced intervention use increased significantly over time. Between 2017 and 2022, proportions with advanced interventions ranged from 12.7 to 27.9%. However, this proportion escalated in late 2023 (55.3%) and ranged from 32.4 to 54.6% in 2024. This rise coincided with increased use of CDI, particularly mechanical thrombectomy, which rose from negligible use before 2023 to nearly one-third of patients (31.8%) in the second half of 2024. Clinical deterioration increased over the study period, with the highest proportions observed in 2024 (27.3–27.9%), compared to an average of 10–18% in prior years. The proportion with major bleeding was highest (21.6%) when the CODE PE program started in 2017, with a variable range over the 8-year study period of 3.1–21.6%.

Table 8 Proportions with advanced intervention use, clinical deterioration, and major bleeding over time

Fig. 7

Figure 7: Proportions of CODE PE activations with advanced intervention use, clinical. deterioration, and major bleeding over time.

Table 9 Shows most outcomes demonstrated statistically significant and nonlinear trends over time. Use of advanced interventions, including CDI (EDF = 5.12, p < 0.001), CDT (EDF = 7.19, p < 0.001), and mechanical thrombectomy (EDF = 8.16, p < 0.001), all demonstrated significant and highly nonlinear Temporal patterns. In contrast, systemic thrombolysis did not show a significant Temporal trend and followed a linear trajectory (EDF = 1.00, p = 0.43). Clinical deterioration exhibited a moderately nonlinear and statistically significant trend (EDF = 1.84, p = 0.008). Major bleeding (EDF 7.28, p < 0.001) fluctuated significantly over time . Visual depictions of these predicted proportions with trends are provided in Fig. 8.

Table 9 Temporal trends for process outcomes and clinical outcomes

Fig. 8

Predicted probabilities of outcomes over time

Discussion

In this regional PERT program, we observed no significant aggregate differences in clinical outcomes between patients who initially presented to PE referral centers versus non-referral centers. CODE PE activations at non-referral centers (N = 946) were triaged by centralized critical care consultants who coordinated the transfer of 534 patients (56.4%) to a PE referral center. Although transferred patients had higher PE severity and were more likely to receive advanced interventions, their rates of clinical deterioration (15.9% vs. 12.9%, p = 0.20) and major bleeding (7.5% vs. 6.3%, p = 0.52) were similar to CODE PE patients who were not transferred from non-referral centers. These findings suggest the triage and transfer process effectively identified patients with more severe PE who could benefit from advanced therapy. Despite timely transfers, transferred patients experienced longer times to start some advanced interventions (Table 4), so opportunities remain to streamline the transfer process. Hospital LOS did not differ significantly between groups, suggesting the interhospital transfer did not prolong overall hospitalization.

When comparing referral centers, key variations were noted in both patient characteristics and treatment practices. The academic center (Hospital B) treated a higher proportion of patients with massive PE and used systemic thrombolysis more frequently than the other two referral centers. Higher use of systemic thrombolysis likely reflects greater comfort with administering tissue plasminogen activator medications, with support of academic center resources (e.g., neurosurgical back-up) in case of complications. CDIs, on the other hand, were performed at Hospitals A and C more often than at the academic center. This likely reflects institutional or provider practice patterns and fewer resources for managing major bleeding complications like intracranial hemorrhage associated with systemic thrombolysis, leading to greater reliance on catheter-based therapies. Despite treatment differences, overall advanced intervention rates were similar across the three centers, suggesting that institutional resources and comfort levels influenced intervention preferences without affecting access to escalation of care. Significant differences in clinical deterioration, though, were observed across the referral centers, with the academic center (Hospital B) having the highest rate. This likely reflects the academic center’s role as a tertiary hub receiving the most critically ill patients, including those requiring ECMO for refractory cardiogenic shock. PE-related death followed a similar trend, with Hospital B having the highest rate among the referral centers.

Our temporal analysis of the entire database (all eight years of the multi-center regional PERT program) revealed three key trends: (1) prompt treatment times for anticoagulation and systemic thrombolysis over time, (2) CDI usage increased and time to CDI decreased, and (3) clinical deterioration increased slightly after early 2023. While times to start of initial anticoagulation remained consistently prompt, times to start of advanced interventions were more variable, especially in the earlier years when therapies, such as CDT and mechanical thrombectomy, were less commonly employed. However, in recent years, a notable trend toward faster initiation of these procedures was observed, reflecting growing institutional familiarity and improved procedural readiness. Over the study period, we observed a gradual increase in clinical deterioration, which may be explained by the increase in PE severity after our CODE PE activation criteria were changed in March 2023 to exclude patients with non-severe submassive PE. This change coincided with increased use of advanced interventions starting in 2023, particularly CDT and mechanical thrombectomy. This trend likely reflects evolving practice patterns and increased use of endovascular techniques, and aligns with emerging evidence at the national level about use of CDT and mechanical thrombectomy in PE [14, 26,27,28,29].

Our study fills gaps in the literature regarding PERT implementation and evaluation. Unlike prior single-center studies that included low-risk PE patients and evaluated a limited set of outcomes over short periods of time post-PERT implementation, we studied eight years’ of ED data from large, multi-center PERT program with consistent inclusion of patients with RVD criteria [1, 24,25,26,27]. Our previous research revealed variability in PE severity, treatment, and outcomes across institutions in our regional PERT [15, 28]. Building on those findings, this study adds insight and granularity into operational efficiencies, such as intervention timing, decision-making, and care transitions between non-referral and referral centers.

Another strength of our study is the temporal trend analysis of both process outcomes and clinical outcomes within an evolving, multi-center, regional PERT. This approach enabled us to report with granularity on any fluctuating or sustained improvements or deterioration in outcomes over a span of eight years. Only a few others have published temporal changes in outcomes associated with PERT. Thomas et al. used two databases to report monthly temporal trends in PE diagnoses (in two hospitals over three years) and PERT activations (in one hospital over three years); however, they did not assess process outcomes or clinical outcomes [26]. Chopard et al. reported temporal trends in their single-center post-PERT implementation study that included 425 patients over 5 years (2015–2019). They found a gradual increase in PE severity, increased use of unfractionated over low molecular weight heparin, greater use of systemic thrombolysis, and reductions in mortality (not clinical deterioration), major bleeding, and hospital readmission [25].

A next step might be to explore the differences we found in clinical deterioration across the three PE referral centers to determine contributing factors (e.g., local practices, resource availability). We recommend future research on PERTs include post-discharge outcomes, such as anticoagulation adherence, cardiopulmonary function, and quality of life. Future PERT evaluations could cumulatively result in outcome benchmarks for a national designation for centers of excellence in PE care or regional PE referral centers.

Limitations

This study had several limitations. First, we did not objectively assess provider rationale for transferring patients or using advanced interventions, nor did we capture the sequence of events (i.e., we did not know if patients received advanced interventions due to PE severity or if advanced interventions were needed because the patient experienced clinical deterioration). During data extraction, we noted the absence of a standardized PERT consultation checklist. Ideally, such a checklist would document PE severity, bleeding risk assessment, considerations for each type of advanced intervention based on individual patient profile, and a synopsis of initial therapies administered in the ED. Although our centralized VCC verifies PE severity using institutional CODE PE severity criteria and facilitates multidisciplinary consultation and transfers for patients who present to non-referral centers, a standardized PERT consultation checklist would improve documentation for quality improvement and evaluation purposes. Capturing more granular PERT decision data could also enable assessment of provider concordance and patient-centered outcomes. Second, as an observational study, confounding factors such as provider experience, local protocols, and timing of transfer decisions may have influenced results. Third, race, ethnicity, and sex data were extracted from the EMR rather than self-reported, which may reduce accuracy [29, 30]. Fourth, while we captured important short-term and longer-term (30-day) clinical outcomes, other post-discharge complications (e.g., quality of life, cardiopulmonary fitness) were not assessed. Fifth, our data capture for major bleeding used an International Society on Thrombosis and Hemostasis definition, which did not account for complications that may be associated with catheter-directed procedures [21]. Sixth, although we reported temporal trends in outcomes for all centers within the regional PERT, we did not report on site-specific trends to determine if changes were uniform or center dependent.

Our findings may not generalize to other health systems with newer, less mature PERT programs, those lacking robust transfer pathways, or PERT programs with different activation criteria. Our modified PE risk stratification, which splits submassive PE into severe submassive and non-severe submassive PE classifications, was based on local experience and informed decisions on how our CODE PE algorithm was operationalized. The shift in some results that coincided with our exclusion of non-severe submassive PE is useful information to share with other PERT programs. Finally, our regional PERT uses centralized oversight rather than a traditional 24/7 on-call, on-site PERT, which may limit comparability.

Conclusions

In our regional PERT with a centralized triage and transfer process, we found no significant aggregate differences in process outcomes or clinical outcomes between patients presenting to referral versus non-referral centers. There were significant differences in PE severity and clinical deterioration across referral centers. While advanced intervention use was consistent across referral centers, the selected type of advanced intervention varied. There were temporal changes in both the selection of and times to start of advanced interventions, with some interventions being more rapidly deployed or used variably over time. Temporal analysis showed our PERT’s shift to focus only on higher acuity PE coincided with increased CDI use, whereas systemic thrombolysis rates and timely start of first heparin were sustained. Aggregate and temporal reporting of process outcomes and clinical outcomes from other PERT programs would highlight evolution in PERTs and improve PERT evaluation, with the aim of continually improving PERTs’ operational efficiency and effectiveness.