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      The incidence of acute pulmonary embolism following syncope in anticoagulant-naïve patients: A retrospective cohort study

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          Abstract

          Background

          A recently published, large prospective study showed unexpectedly high prevalence of acute pulmonary embolism (APE) among patients hospitalized for syncope. In such a case, a high incidence of recurrent pulmonary embolism is expected among patients who were discharged without APE workup.

          Objectives

          To determine the incidence of symptomatic APE among patients hospitalized for a first episode of syncope and discharged without APE workup or anticoagulation.

          Methods

          This retrospective cohort study included patients hospitalized at Rambam Health Care Campus between January 2006 and February 2017 with a primary admission diagnosis of syncope, who were not investigated for APE and were not taking anticoagulants. The patients were followed up for up to three years after discharge. The occurrence of venous thromboembolism (VTE) during the follow-up period was documented.

          Results

          The median follow-up duration was 33 months. 1,126 subjects completed a three-year follow-up. During this period, 38 patients (3.38%) developed VTE, 17 (1.51%) of them had APE. The cumulative incidence of VTE and APE was 1.9% (95% CI 1.3%-2.5%) and 0.9% (95% CI 0.4%-1.3%) respectively. Only seven subjects developed APE during the first year of follow-up. The median times from the event of syncope to the development of APE and VTE were 18 and 19 months respectively.

          Conclusions

          The cumulative incidence of VTE during a three-year follow-up period after an episode of syncope is low. In the absence of clinical suspicion, a routine diagnostic workup for APE in patients with syncope cannot be recommended.

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          Most cited references28

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          2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.

          Stavros V Konstantinides, Adam Torbicki, Giancarlo Agnelli … (2014)
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            Multidetector computed tomography for acute pulmonary embolism.

            Paul Stein, Sarah E. Fowler, Lawrence Goodman … (2006)
            The accuracy of multidetector computed tomographic angiography (CTA) for the diagnosis of acute pulmonary embolism has not been determined conclusively. The Prospective Investigation of Pulmonary Embolism Diagnosis II trial was a prospective, multicenter investigation of the accuracy of multidetector CTA alone and combined with venous-phase imaging (CTA-CTV) for the diagnosis of acute pulmonary embolism. We used a composite reference test to confirm or rule out the diagnosis of pulmonary embolism. Among 824 patients with a reference diagnosis and a completed CT study, CTA was inconclusive in 51 because of poor image quality. Excluding such inconclusive studies, the sensitivity of CTA was 83 percent and the specificity was 96 percent. Positive predictive values were 96 percent with a concordantly high or low probability on clinical assessment, 92 percent with an intermediate probability on clinical assessment, and nondiagnostic if clinical probability was discordant. CTA-CTV was inconclusive in 87 of 824 patients because the image quality of either CTA or CTV was poor. The sensitivity of CTA-CTV for pulmonary embolism was 90 percent, and specificity was 95 percent. CTA-CTV was also nondiagnostic with a discordant clinical probability. In patients with suspected pulmonary embolism, multidetector CTA-CTV has a higher diagnostic sensitivity than does CTA alone, with similar specificity. The predictive value of either CTA or CTA-CTV is high with a concordant clinical assessment, but additional testing is necessary when the clinical probability is inconsistent with the imaging results. Copyright 2006 Massachusetts Medical Society.
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              Natural history of venous thromboembolism.

              Clive Kearon (2003)
              Most deep vein thromboses (DVTs) start in the calf, and most probably resolve spontaneously. Thrombi that remain confined to the calf rarely cause leg symptoms or symptomatic pulmonary embolism (PE). The probability that calf DVT will extend to involve the proximal veins and subsequently cause PE increases with the severity of the initiating prothrombotic stimulus. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Proximal DVTs resolve slowly during treatment with anticoagulants, and thrombi remain detectable in half of the patients after a year. Resolution of DVT is less likely in patients with a large initial thrombus or cancer. About 10% of patients with symptomatic DVTs develop severe post-thrombotic syndrome within 5 years, and recurrent ipsilateral DVT increases this risk. About 10% of PEs are rapidly fatal, and an additional 5% cause death later, despite diagnosis and treatment. About 50% of diagnosed PEs are associated with right ventricular dysfunction, which is associated with a approximately 5-fold greater in-hospital mortality. There is approximately 50% resolution of PE after 1 month of treatment, and perfusion eventually returns to normal in two thirds of patients. About 5% of treated patients with PE develop pulmonary hypertension as a result of poor resolution. After a course of treatment, the risk of recurrent thrombosis is higher (ie, approximately 10% per patient-year) in patients without reversible risk factors, in those with cancer, and in those with prothrombotic biochemical abnormalities such as antiphospholipid antibodies and homozygous factor V Leiden.
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                Author and article information

                Contributors
                Danny Epstein:
                ORCID: http://orcid.org/0000-0001-7032-7007
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Gidon Berger: Role: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Noam Barda: Role: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Erez Marcusohn: Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Yuval Barak-Corren: Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Khitam Muhsen: Role: MethodologyRole: Writing – review & editing
                Ran D. Balicer: Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – review & editing
                Zaher S. Azzam: Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – original draft
                Stelios Loukides: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 7 March 2018
                Publication date Collection: 2018
                Volume: 13
                Issue: 3
                Electronic Location Identifier: e0193725
                Affiliations
                [1 ] Department of Internal Medicine "B", Rambam Health Care Campus, Haifa, Israel
                [2 ] Division of Pulmonary Medicine, Rambam Health Care Campus, Haifa, Israel
                [3 ] Clalit Research Institute, Chief Physician’s Office, Clalit Health Services, Tel Aviv, Israel
                [4 ] Predictive Medicine Group, Boston Children’s Hospital, Boston, United States of America
                [5 ] Shaare Tzedek Medical Center, Jerusalem, Israel
                [6 ] Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
                [7 ] Epidemiology Department, Ben Gurion University of the Negev, Be’er Sheba, Israel
                [8 ] The Rappaport's Faculty of Medicine, The Technion Institute, Haifa, Israel
                National and Kapodistrian University of Athens, GREECE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-7032-7007
                Article
                Publisher ID: PONE-D-17-43926
                DOI: 10.1371/journal.pone.0193725
                PMC ID: 5841762
                PubMed ID: 29513729
                SO-VID: 50540f26-8594-45f1-b305-07da0a3404a7
                Copyright © © 2018 Epstein et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 16 December 2017
                Date accepted : 19 February 2018
                Page count
                Figures: 2, Tables: 3, Pages: 12
                Funding
                The authors received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Signs and Symptoms
                Subject: Syncope
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Signs and Symptoms
                Subject: Syncope
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Thromboembolism
                Subject: Venous Thromboembolism
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Etiology
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Pulmonary Embolism
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Thromboembolism
                Subject: Venous Thromboembolism
                Subject: Pulmonary Embolism
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Thromboembolism
                Subject: Venous Thromboembolism
                Subject: Deep Vein Thrombosis
                Subject: Medicine and Health Sciences
                Subject: Health Care
                Subject: Health Care Facilities
                Subject: Hospitals
                Subject: Hospitalizations
                Subject: Research and Analysis Methods
                Subject: Bioassays and Physiological Analysis
                Subject: Electrophysiological Techniques
                Subject: Cardiac Electrophysiology
                Subject: Electrocardiography
                Custom metadata
                Data Availability The only information which can not be found in the manuscript or the supporting files is the demographic and clinical characteristics of each patient diagnosed with VTE during the follow up period. The reason for this restriction is the small number of patients diagnosed with VTE (n = 38). According to the decision of Institutional Review Board at CHS, providing full information regarding each patient in this small group can potentially lead to their identification and compromise their confidentiality. The statistical analysis of this information can be found in Table 2 in the main manuscript. The full information regarding majority of patients diagnosed with APE is shown in Table 3. The request for this information can be sent to Clalit Research Institute, 101 Arlozorov Street, Tel Aviv, ZIP 6209804, Israel, by Tel: +972-3-6925800, by Fax: +972-3-6925821 or via contact us link http://clalitresearch.org/contact.

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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