|Year : 2021 | Volume
| Issue : 2 | Page : 40-44
Impact of registry implementation on the management and survival of patients with pulmonary embolism
Omid Shafe1, Jamal Moosavi1, Azin Alizadehasl2, Hamid Reza Pouraliakbar3, Batoul Naghavi3, Sepehr Jamalkhani3, Saied Rezaei3, Kiara Rezaei-Kalantari3, Melody Farrashi2, Mona Naghshbandi2, Parham Rabiei3, Majid Maleki1, Hamed Talakoob3, Maryam Mohseni Salehi3, Mahfam Malakouti3, Parham Sadeghipour1
1 Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
2 Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
3 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
|Date of Submission||25-Jan-2021|
|Date of Decision||06-May-2021|
|Date of Acceptance||12-May-2021|
|Date of Web Publication||29-Jul-2021|
Dr. Parham Sadeghipour
Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Vali-Asr Ave, Tehran 1995614331
Source of Support: None, Conflict of Interest: None
Background: Pulmonary embolism (PE) is a major public health concern, with a considerable mortality rate. In the present study, we have evaluated the impact of registry implementation on PE management. Methods: In the present single-center study, composed of two distinct cohorts, we have evaluated the impact of registry implementation (prospective arm-September 2015 to August 2018) on patient management and survival, and compared it with the same duration when no registry was implied (retrospective arm-September 2012 to August 2015). Results: One hundred and seventy and 182 patients were recruited in the prospective and retrospective arms, respectively. Guideline-recommended risk stratification was significantly overlooked before the introduction of PE registry (100% vs. 45.6% prospective and retrospective arms, respectively [P < 0.001]). A trend toward higher administration of thrombolytic therapy was noted in patients admitted during the registry time (20 [64.5%] vs. 3 [37.5%], P = 0.166). The registry had also significant impact on length of hospital stay (6.72 ± 4.39 days versus 9.35 ± 5.55, P = 0.001, in prospective and retrospective arms, respectively). No significant difference was detected on the 6-month all-cause mortality. However, re-venous thromboembolism was significantly reduced during registry time (2 [1.2%) vs. 22 [12.2%], P < 0.001). Finally, significantly more patients underwent guideline-recommended follow-up during the registry time (107 [72.3%] vs. 30 [16.5%], P < 0.001). Conclusion: Our study showed the implementation of registry had significant effect on PE-related outcome and might have direct impact on burden of pulmonary emboli on the healthcare system.
Keywords: Clinical registry, pulmonary embolism, risk stratification, thrombolytic therapy
|How to cite this article:|
Shafe O, Moosavi J, Alizadehasl A, Pouraliakbar HR, Naghavi B, Jamalkhani S, Rezaei S, Rezaei-Kalantari K, Farrashi M, Naghshbandi M, Rabiei P, Maleki M, Talakoob H, Salehi MM, Malakouti M, Sadeghipour P. Impact of registry implementation on the management and survival of patients with pulmonary embolism. Res Cardiovasc Med 2021;10:40-4
|How to cite this URL:|
Shafe O, Moosavi J, Alizadehasl A, Pouraliakbar HR, Naghavi B, Jamalkhani S, Rezaei S, Rezaei-Kalantari K, Farrashi M, Naghshbandi M, Rabiei P, Maleki M, Talakoob H, Salehi MM, Malakouti M, Sadeghipour P. Impact of registry implementation on the management and survival of patients with pulmonary embolism. Res Cardiovasc Med [serial online] 2021 [cited 2021 Dec 4];10:40-4. Available from: https://www.rcvmonline.com/text.asp?2021/10/2/40/322584
| Introduction|| |
Pulmonary embolism (PE) is considered one of the leading causes of cardiovascular mortality and morbidity. Despite the recent advancements in the management of PE, we still suffer from global poor applicability of the proven standard of care. As shown in the initial report from EMPEROR (Emergency Medicine Pulmonary Embolism in the Real World Registry) registry, echocardiography and cardiac biomarkers measurement-serum troponin and brain natriuretic peptide (BNP) or NT-proBNP were performed in 23%, 68%, and 35%, respectively. Importantly, only three of the twenty patients who died of high-risk PE, had received systemic thrombolytic therapy.
Clinical registries were first introduced as a meticulous and structural way to recruit patient data for research purposes. Besides, by offering a rigorous patient monitoring, registries are intended to improve patient care and survival which eventually lead to reduced healthcare cost and can ameliorate the burden of diseases. However, few studies have truly evaluated the impact of registries as a tool for improving health care. Furthermore, since registry establishments are costly, it is essential to demonstrate their benefits.
In early 2015, the global experience regarding the activation of the pulmonary emboli response team (PERT) and also the introduction of catheter-directed thrombolysis (CDT) in patients with PE as an emerging therapy, prompted us to incorporate the mentioned discipline in our own hospital. After treating thirty patients through CDT, we realized that some preliminary steps needed to be taken before incorporating PERT in our system. The list of the necessary measures included the compilation of local protocols based on the latest guideline recommendations regarding the diagnosis, risk stratification, treatment, and follow-up of patients with PE, along with a strong electronic datastorage system. We hypothesized that the establishment of a PE registry would act as a tool to ameliorate our data collection, enhance the administration of the protocols by local practitioners, and consequently improve the quality of care and provide the necessary backgrounds and infrastructures for implementing PERT or advanced treatment modalities such as CDT.
| Methods|| |
In the present study, consisted of two distinct cohorts, we have evaluated the impact of registry implementation (prospective arm: September 2015 to August 2018) on patients' management and survival rates and compared it with a similar duration preceding the launch of the registry (retrospective arm: September 2012 to August 2015). The population of both the prospective and retrospective arms consisted of all consecutive patients with a confirmed diagnosis of PE admitted in the Rajaie Cardiovascular Medical and Research Center (RHC) (Tehran, Iran) during each of the mentioned time periods. The diagnosis of PE was made primarily based on pulmonary computed tomography angiography results. Lung perfusion scan was used for PE confirmation in patients with chronic kidney disease or allergy to iodine contrast. The study has been approved by RHC ethical committee. All prospectively recruited patients signed a written informed consent form before participation. For the retrospective arm, relevant data were collected from medical records. Six-month follow-up data on each group was used for comparison. For the retrospective arm, apart from relying on available data on patients' medical records and outpatient visits, patients were contacted by phone call in order to improved assessment of the 6-month follow-up outcomes.
Patients admitted with PE were categorized as low-, intermediate-low, intermediate-high, and high-risk according to the guidelines of the European Society of Cardiology. A detailed guideline-recommended risk stratification (GRS) model was applied early after admission and PE confirmation, consisting of the levels of biomarkers (N-terminal pro-B-type natriuretic peptide and troponin), transthoracic echocardiography (TTE), and the calculation of the Pulmonary embolism severity index score. The right ventricle/left ventricle ratio and the presence of right heart thrombi were especially noted in the initial TTE.
An advanced therapeutic strategy was selected according to the latest recommendations and clinical judgment. Our main thrombolytic strategy was CDT, and systemic thrombolytic therapy was reserved for patients whose transfer to the cath laboratory was judged too risky. Those with fresh right heart thrombi were also candidated for advanced therapy. When clots in transit from the foramen ovale were ruled out, thrombolytic therapy was considered to be the primary therapy.
Apart from the TTE performed on early admission, each patient underwent a second detailed TTE, in which guideline-recommended and investigational echocardiographic indices were measured.
A structured 6-month follow-up program was designed. Each participant was invited for the follow-up sessions through phone calls. The follow-up sessions were comprised a detailed TTE examination, a 6-min walk test, and the filling out of the 36-Item Short Form Survey and pulmonary embolism Quality of Life questionnaires. During the visits, medication adherence was actively evaluated and relevant recommendations were applied. In addition, a brief update of the patients' condition and future directions were explained to them and their companions.
In the descriptive analysis of the patients' baseline characteristics and study outcomes, percentages were used for the categorical variables. All the numeric data are expressed as the mean ± the standard deviation for the parametric variables, while the parameters without normal distributions are expressed as the median with the interquartile range.
Qualitative data were compared using the Chi-squared test. The Mann–Whitney test was used to analyze the data without normal distributions, whereas the normally distributed data were analyzed using the student t-test with a 95% confidence interval for their differences.
Univariate linear regression was utilized to evaluate the relationship between complete recovery at 6 months and different parameters at baseline.
P < 0.05 was considered statistically significant. All the analyses were conducted using SPSS 18 (SPSS Inc., Chicago, IL, USA).
| Results|| |
The prospective and retrospective arms contained 170 and 182 patients, respectively. The demographic and clinical characteristics of both arms are summarized in [Table 1] and [Figure 1]. GRS was overlooked significantly before the introduction of the PE registry (100% vs. 45.6% in the prospective and retrospective arms, correspondingly; P < 0.001). Interestingly, before the registry implementation, the levels of N-terminal pro-B-type natriuretic peptide and troponin were checked only in 83 (45.6%) and 24 (13.2%) patients, respectively, in the acute setting. Consequently, owing to inaccurate GRS in our retrospective analysis, only high-risk patients who were defined based on hemodynamic instability were identifiable and it was not possible to determine the exact percentages of the patients which would be allocated to the low-risk and intermediate-risk categories. Of note, a significantly larger percentage of the patients were stratified as high-risk (massive) PE after the registry implementation (31 [18.2%] vs. 8 [4.4%]; P < 0.001). A trend toward a more frequent administration of thrombolytic therapy (consisted of both systemic intravenous thrombolytics and CDT) was noted in the patients admitted during the registry time (20 of 31 [64.5%] vs. 3 of 8 [37.5%]; P = 0.166). In-hospital major bleeding in the prospective arm was limited to one patient. (The patient underwent CDT and subsequently fully recovered.) Unfortunately, our inability to collect reliable information regarding thrombolytic-related major bleeding in our retrospective analysis rendered a comparison impossible. The registry also had a significant impact on hospital stay reduction (6.72 ± 4.39 days in the prospective arm vs. 9.35 ± 5.55 days in the retrospective arm; P = 0.001). Anticoagulation regimens during the two different timelines are presented in [Table 2]. Of note, 45 (51.7%) of the patients with intermediate-high and high-risk PE were treated with novel oral anticoagulation. Inferior vena cava filter was used for only one patient during the registry time, compared with seven patients in the preceding period (P = 0.040). No significant difference was detected concerning 6-month all-cause mortality before and after the registry implementation (18 [9.9%] vs. 12 [7.1%]; P = 0.342). However, the recurrence of venous thromboembolism (Re-VTE), defined as any reoccurrence of PE or DVT proven by imaging, was significantly reduced during the registry time (2 [1.2%] vs. 22 [12.2%]; P < 0.001). Finally, significantly more patients underwent guideline-recommended follow-up in the form of echocardiography at 3–6 months during the registry time (123 [72.3%] vs. 30 [16.5%]; P < 0.001). Importantly, the 6-min walk test was performed for 104 patients, of whom 32 (30.7%) had a score of <330 meters.
|Figure 1: Impact of pulmonary emboli registry implementation. *Statistically significant difference, 1, guideline-recommended risk stratification; 2, thrombolytic therapy; 3, length of hospital stay; 4, re-venous thromboembolism; 5, guideline-recommended follow-up; 6, 6-month all-cause mortality|
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|Table 1: Demographic and clinical characteristics of studied population before and after registry implementation|
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|Table 2: In-hospital management of studied population before and during the registry implementation|
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| Discussion|| |
In the present report, we have shown that the implementation of a PE registry had a significant impact on multiple PE-related outcomes that might have a direct bearing on the burden of the disease, and can be recognized as a tool for quality improvement. Clinical registries are generally deemed a practical tool for improving medical care and its cost-effectiveness. There is, nonetheless, a dearth of research into the impact of registries. Indeed, investigators and sites that have significantly invested in the establishment of registries have thus far been disinclined to formally evaluate their impact through rigorous trial designs because of the considerable financial resources required for the infrastructure and viability of registries. Consequently, this quality assessment in each specific clinical scenario is of utmost importance. Various ranges of presentation, different clinical scenarios, and unresolved therapeutic dilemmas have made the diagnosis and treatment of PE essentially challenging. Notwithstanding the essential role of clinical guidelines in categorizing the best available evidence and delineating the standard of care, their applicability in the medical community is heterogeneous. Recent data from a large multicenter registry showed that the management of patients with PE was still inadequately standardized and that the proven evidence-based therapies were still underutilized (i.e., only 9% administration of systemic thrombolytics in high-risk PE). Our retrospective analysis confirmed this finding and revealed a poor application of GRS (46.5%) in early admission and also the underutilization of thrombolytic therapy in high-risk patients (37.5%). Standard risk stratification may be considered an evident truth in the management of PE, but it has been clearly underutilized, even in the four pivotal studies on the role of novel oral anticoagulation in patients with VTE. The Hokusai-VTE study is the only trial incorporating both N-terminal pro-B-type natriuretic peptide levels and imaging as criteria for right ventricular function. Interestingly, our observation showed that the application of both GRS and thrombolytic therapy was increased with the implementation of the PE registry. Furthermore, apart from improving the standard of care, the registry was successful in reducing unnecessary procedures (i.e., deployment of the inferior vena cava filter). The present report is certainly not powered to delineate the exact causality of the observed benefits. Constant data monitoring and supervised data transparency offered by the registries might be a plausible explanation for the presumed observation., Furthermore, the new interest in venous diseases during recent years, might also influence the increased use of reperfusion therapy. The introduction of new modalities such as CDT and new thrombolytic regimen such as half dose options has created an enthusiasm for physicians to treat PE beyond anticoagulation.
Registries may also help to outline future directions. For instance, as much as the 68% application rate of thrombolytic therapy in the present study might be regarded as a success, there is still room for improvement. A review of the characteristics of the patients who did not receive thrombolytic therapy might help draw possible justifications needed to fill the therapeutic gaps. By way of example, Todoran et al. showed that while physicians generally approved of the criteria for right ventricular dysfunction and biomarkers, they did not consider all types of hypotension to be similarly severe, which might result in the underutilization of thrombolytic therapy in high-risk populations. Clinical registries have an important role in the areas of clinical uncertainties to which randomized controlled trials are hard to apply. Our institutional approach was concentrated on surgical management for concomitant right heart thrombosis [Table 2]; nevertheless, the successful application of thrombolytic therapy in the right heart thrombi that were not in transit (as demonstrated by our PE registry) has tempered some initial strong arguments.
In recent years, the pulmonary embolism response team (PERT) has been introduced as a multidisciplinary platform to assist physicians in providing better care for patients with PE. Our experience suggests that a clinical registry might be considered as a prerequisite of the PERT program to provide the necessary background for PERT implication., although authentic and novel, needs sustained funding for infrastructure and clinicians' time and thus, such as clinical registries, its impact on the quality of care and cost-effectiveness should be tested. Since no randomized controlled trials have yet elaborated on the matter, a structuralized registry with realistic outcomes appears to be the best method for this quality assessment. In addition, granted that PERT underscores the importance of follow-up in patients with PE, still, its main effort is concentrated on implementing new treatment modalities, especially in high-risk and/or complicated patients –in the index event. Our PE registry has successfully Importantly, our PE registry has influenced the quality of the follow-up, which is usually overlooked in PERT. After implication of the registry, we managed to increase the 6-month follow-up rate by 72.3%, which can be translated to an earlier detection of patients at risk for chronic consequences of PE and especially chronic thromboembolic pulmonary hypertension, Recent studies have shown that because the PE-induced functional limitation involves nearly half of the affected population and not just high-risk patients, it creates broad socioeconomic consequences. The registry offers a structural program for evaluating the right ventricular function, exercise capacity, and quality of life with a view to depicting a clear picture of the patient's current situation for both patient and physician. We believe that this realistic picture plays an important role in further management measures such as the evaluation of chronic thromboembolic pulmonary hypertension and the continuation/discontinuation of anticoagulation. Finally, we have also reported an important decrease in the rate of the VTE recurrence during the registry time. Vis-à-vis this finding, the possible role of the following factors should be taken into account: the value of novel oral anticoagulation in the real-world setting, the value of follow-up programs in medication adherence (which actually has been shown to diminish over time), and family awareness during follow-up sessions.
First and foremost among the limitations of the present study is its observational nature, followed by its limited sample size, which might have influenced the results. Another salient drawback is that our study lacks a cost-benefit analysis, although it demonstrates a reduction in the length of hospital stay and the rate of VTE recurrence with their potential cost impacts. Furthermore, we have collected retrospectively the 6-month related outcomes before the registry implementation, which again might impact our comparison between the two time periods. Finally, the current study is underpowered to evaluate the role of other contributors than registry implantation in the improvement of the management of PE. Various factors such as the introduction of new treatment modalities, especially novel oral anticoagulation and the increase social awareness regarding PE have certainly positive role in decreasing the burden of pulmonary emboli.
| Conclusion|| |
Our study showed the implementation of registry in our hospital had significant effect on PE-related outcome specially GRS and invasive management of PE. More patients were followed. Th potential impact of mentioned improved outcomes should be tested in large trials.
The study has been approved by Rajaie Cardiovascular Medical and Research Center ethical committee. The Ethical approval number is RHC-95082 approved on September 2015.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al.
2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020;41:543-603.
Pollack CV, Schreiber D, Goldhaber SZ, Slattery D, Fanikos J, O'Neil BJ, et al.
Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: Initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol 2011;57:700-6.
Hoque DM, Kumari V, Ruseckaite R, Romero L, Evans SM. Impact of clinical registries on quality of patient care and health outcomes: protocol for a systematic review. BMJ Open 2016;6:e010654.
Rosovsky R, Zhao K, Sista A, Rivera-Lebron B, Kabrhel C. Pulmonary embolism response teams: Purpose, evidence for efficacy, and future research directions. Res Pract Thromb Haemost 2019;3:315-30.
Hoque DME, Kumari V, Hoque M, Ruseckaite R, Romero L, Evans SM. Impact of clinical registries on quality of patient care and clinical outcomes: A systematic review. PLoS One 2017;12:e0183667.
Rivera-Lebron B, McDaniel M, Ahrar K, Alrifai A, Dudzinski DM, Fanola C, et al.
Diagnosis, treatment and follow up of acute pulmonary embolism: Consensus practice from the PERT consortium. Clin Appl Thromb Hemost 2019;25:1076029619853037.
Cohn DM, Nelis EA, Busweiler LA, Kaptein AA, Middeldorp S. Quality of life after pulmonary embolism: The development of the PEmb-QoL questionnaire. J Thromb Haemost 2009;7:1044-6.
Brekelmans MP, Ageno W, Beenen LF, Brenner B, Buller HR, Chen CZ, et al.
Recurrent venous thromboembolism in patients with pulmonary embolism and right ventricular dysfunction: A post-hoc analysis of the Hokusai-VTE study. Lancet Haematol 2016;3:e437-45.
Bikdeli B, Jimenez D, Hawkins M, Ortiz S, Prandoni P, Brenner B, et al.
Rationale, design and methodology of the computerized registry of patients with venous thromboembolism (RIETE). Thromb Haemost 2018;118:214-24.
Todoran TM, Giri J, Barnes GD, Rosovsky RP, Chang Y, Jaff MR, et al.
Treatment of submassive and massive pulmonary embolism: A clinical practice survey from the second annual meeting of the Pulmonary Embolism Response Team Consortium. J Thromb Thrombolysis 2018;46:39-49.
Moosavi J, Shafe O, Alizadehasl A, Parsaee M, Sadeghpour A, Khesali F, et al.
Half-dose thrombolytic therapy in patients with right heart thrombi. J Int Med Res 2019;47:3400-7.
Kahn SR, Hirsch AM, Akaberi A, Hernandez P, Anderson DR, Wells PS, et al.
Functional and exercise limitations after a first episode of pulmonary embolism: Results of the ELOPE prospective cohort study. Chest 2017;151:1058-68.
[Table 1], [Table 2]