Pulmonary rehabilitation to improve physical capacity, dyspnea, and quality of life following pulmonary embolism (the PeRehab study): study protocol for a two-center randomized controlled trial

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The venous thrombosis registry in Østfold Hospital (TROLL registry) - design and cohort description

Purpose: The incidence of venous thromboembolism (VTE) is expected to increase over the next decades, further increasing its substantial impact on patients and health care resources. Registries have the benefit of reporting real-world data without excluding clinically important subgroups. Our aim was to describe a Norwegian VTE registry and to provide descriptive data on the population and management. Registry Population: The Venous Thrombosis Registry in Østfold Hospital (TROLL) is an ongoing registry of consecutive patients diagnosed with, treated, and/or followed up for VTE at Østfold Hospital, Norway, since 2005. Baseline and follow-up data, including demographics, clinical features, risk factors, diagnostic procedures, classification of VTE, and treatment were collected during hospitalization, and at scheduled outpatient visits. Findings to Date: From January 2005 to June 2021, 5037 patients were eligible for research in TROLL. Median age was 67 years (interquartile range, 55–77), and 2622 (52.1%) were male. Of these, 2736 (54.3%) had pulmonary embolism (PE), 2034 (40.4%) had deep vein thrombosis (DVT), and 265 (5.3%) had upper-extremity DVT or splanchnic or cerebral sinus vein thrombosis. In total, 2330 (46.3%) were classified as unprovoked VTE, and 1131 (22.5%) had cancer. Direct oral anticoagulants were the most frequent therapeutic agents (39.3%) followed by low-molecular-weight heparins (30.4%) and vitamin K antagonists (30.3%). Outpatient treatment for PE increased from 4% in 2005 to 23% in 2019. Future Plans: TROLL is a population-based ongoing registry that represents a valuable source of real-world data that will be used for future research on the management and outcomes of VTE

Association between myocardial fibrosis, as assessed with cardiac magnetic resonance T1 mapping, and persistent dyspnea after pulmonary embolism

Background Persistent dyspnea is a common symptom after pulmonary embolism (PE). However, the pathophysiology of persistent dyspnea is not fully clarified. This study aimed to explore possible associations between diffuse myocardial fibrosis, as assessed by cardiac magnetic resonance (CMR) T1 mapping, and persistent dyspnea in patients with a history of PE. Methods CMR with T1 mapping and extracellular volume fraction (ECV) calculations were performed after PE in 51 patients with persistent dyspnea and in 50 non-dyspneic patients. Patients with known pulmonary disease, heart disease and CTEPH were excluded. Results Native T1 was higher in the interventricular septum in dyspneic patients compared to non-dyspneic patients; difference 13 ms (95% CI: 2–23 ms). ECV was also significantly higher in patients with dyspnea; difference 0.9 percent points (95% CI: 0.04–1.8 pp). There was no difference in native T1 or ECV in the left ventricular lateral wall. Native T1 in the interventricular septum had an adjusted Odds Ratio of 1.18 per 10 ms increase (95% CI: 0.99–1.42) in predicting dyspnea, and an adjusted Odds Ratio of 1.47 per 10 ms increase (95% CI: 1.10–1.96) in predicting Incremental Shuttle Walk Test (ISWT) score < 1020 m. Conclusion Septal native T1 and ECV values were higher in patients with dyspnea after PE compared with those who were fully recovered suggesting a possible pathological role of myocardial fibrosis in the development of dyspnea after PE. Further studies are needed to validate our findings and to explore their pathophysiological role and clinical significance

Effects of pulmonary rehabilitation on cardiac magnetic resonance parameters in patients with persistent dyspnea following pulmonary embolism

Background Persistent dyspnea and reduced exercise capacity is common in pulmonary embolism (PE) survivors. Although improved right ventricular function after pulmonary rehabilitation has been demonstrated in chronic thromboembolic pulmonary hypertension, it is still unknown whether a similar effect also occurs in other patients with dyspnea after pulmonary embolism. Purpose The aim of this study was to explore potential effects of a pulmonary rehabilitation program on cardiac structure and function as assessed with cardiac magnetic resonance (CMR). Material and methods Twenty-six PE survivors with persistent dyspnea were included. Right and left ventricular assessment with CMR was performed before and after an eight-week pulmonary rehabilitation program. Results Dyspnea as measured by the Shortness of Breath Questionnaire improved significantly after rehabilitation: 15 (IQR: 7–31) versus 8 (IQR: 3–17). Absolute right ventricular global longitudinal strain by CMR was reduced from 19% to 18% (95% CI of difference: 0–3 percent points), and absolute RV lateral strain from 26% to 24% (95% CI of difference: 1–4 percent points). Right ventricular mass was reduced after rehabilitation from 49 g to 44 g (95% CI of difference: 2–8 g). Conclusion Although there was a substantial improvement in dyspnea after rehabilitation, we found only a minor reduction in absolute right ventricular longitudinal strain and right ventricular mass. No other CMR parameter changed. We therefore suggest that rehabilitation effect of in this patient group was not primarily mediated by cardiac adaptions.publishedVersio

Safety of D-dimer testing as a stand-alone test for the exclusion of deep vein thrombosis as compared with other strategies

Background: Several strategies for safely excluding deep vein thrombosis (DVT) while limiting the number of imaging tests have been explored. Objectives: To determine whether D-dimer testing could safely and efficiently exclude DVT as a stand-alone test, and evalu- ate its performance as compared with strategies that incorporate the Wells score and age-adjusted D-dimer. Patients/Methods: We included consecutive outpatients referred with suspected DVT to the Emergency Depart- ment at Østfold Hospital, Norway. STA-Liatest D-Di PLUS D-dimer was analyzed for all patients. Patients with a D-dimer level of ≥ 0.5 lgmL 1 were referred for compression ultrasonography (CUS). In patients with a D-dimer level of < 0.5 lgmL 1 , no further testing was performed and anticoagulation was withheld. Patients were followed for 3 months for venous thromboembolism (VTE). Results: Of the 913 included patients, 298 (33%) had a negative D-dimer result. One hundred and seventy- three patients (18.9%) were diagnosed with DVT at baseline. One of 298 patients had DVT despite having a negative D-dimer result, resulting in a failure rate of 0.3% (95% confidence interval [CI] 0.1–1.9%). Adding the modified Wells score would have yielded a failure rate of 0.0% (95% CI 0.0–1.8%) while necessitating 87 more CUS examinations. Age-adjusted D-dimer as a stand- alone test would have necessitated 80 fewer CUS exami- nations than fixed D-dimer as a stand-alone test, at the cost of a failure rate of 1.6% (95% CI 0.7– 3.4%). Con- clusions: This outcome study shows that a negative high-sensitivity D-dimer result safely excludes DVT in an outpatient population, and necessitates fewer CUS than if used in combination with Wells score. The safety of stand-alone age-adjusted D-dimer needs further assess- ment in prospective outcome studies

Safety of a strategy combining D-dimer testing and whole-leg ultrasonography to rule out deep vein thrombosis

Abstract Guidelines for the diagnostic workup of deep vein thrombosis (DVT) recommend assessing the clinical pretest probability before proceeding to D-dimer testing and/or compression ultrasonography (CUS) if the patient has high pretest probability or positive D-dimer. Referring only patients with positive D-dimer for whole-leg CUS irrespective of pretest probability may simplify the workup of DVT. In this prospective management outcome study, we assessed the safety of such a strategy. We included consecutive outpatients referred to the Emergency Department at Østfold Hospital, Norway, with suspected DVT between February 2015 and November 2018. STA-Liatest D-Di Plus D-dimer was analyzed for all patients, and only patients with levels ≥0.5 µg/mL were referred for CUS. All patients with negative D-dimer or negative CUS were followed for 3 months to assess the venous thromboembolic rate. One thousand three hundred ninety-seven patients were included. Median age was 64 years (interquartile range, 52-73 years), and 770 patients (55%) were female. D-dimer was negative in 415 patients (29.7%) and positive in 982 patients (70.3%). DVT was diagnosed in 277 patients (19.8%). Six patients in whom DVT was ruled out at baseline were diagnosed with DVT within 3 months of follow-up for a thromboembolic rate of 0.5% (95% confidence interval, 0.2-1.2). A simple diagnostic approach with initial stand-alone D-dimer followed by a single whole-leg CUS in patients with positive D-dimer safely ruled out DVT. We consider this strategy to be a valuable alternative to the conventional workup of DVT in outpatients. This trial was registered at www.clinicaltrials.gov as #NCT02486445

Safety and feasibility of rivaroxaban in deferred workup of patients with suspected deep vein thrombosis

Abstract Guidelines suggest using empiric low-molecular-weight heparin if the diagnostic workup of deep vein thrombosis (DVT) is expected to be delayed. The role of direct oral anticoagulants for deferred compression ultrasound imaging (CUS) in patients with suspected DVT remains unexplored. The main objective of the study was to assess the safety of deferring CUS with therapeutic doses of rivaroxaban. We prospectively included consecutive outpatients referred to the Emergency Department at Østfold Hospital, Norway, with suspected first or recurrent lower-extremity DVT between February 2015 and November 2018. Patients were discharged with rivaroxaban 15 mg twice daily while awaiting CUS within 24 hours if D-dimer level was ≥0.5 mg/L fibrinogen-equivalent units. The primary outcome was the rate of major bleeding incidents from study inclusion until DVT was confirmed and anticoagulation therapy continued, or otherwise up to 48 hours following administration of the last tablet of rivaroxaban. The secondary outcome was the rate of progressive DVT symptoms or symptoms or signs of pulmonary embolism between hospital discharge until venous thromboembolism was diagnosed. Six hundred twenty-four of 1653 patients referred with suspected DVT were included (37.7%; 95% confidence interval [CI], 35.4-40.1). DVT was diagnosed in 119 patients (19.1%; 95% CI, 16.1-22.3). There were no major bleeding incidents, yielding an observed major bleeding rate of 0% (1-sided 95% CI &amp;lt;0.4). No patients experienced major complications in the interval that CUS was deferred (0%; 95% CI, 0.0-0.6). Deferring CUS for up to 24 hours in patients with suspected DVT with therapeutic doses of rivaroxaban is a safe strategy. This trial was registered at www.clinicaltrials.gov as #NCT02486445

The Effects of Exercise Training in Patients With Persistent Dyspnea Following Pulmonary Embolism:A Randomized Controlled Trial

Bakgrunn Vedvarende dyspné, funksjonelle begrensninger og redusert livskvalitet (QoL) er vanlig etter lungeemboli (PE). Rehabilitering er et potensielt behandlingsalternativ , men den vitenskapelige dokumentasjonen er begrenset. Forskningsspørsmål Forbedrer et treningsbasert rehabiliteringsprogram treningskapasiteten hos PE-overlevere med vedvarende dyspné? Studiedesign og metoder Denne randomiserte kontrollerte studien ble utført ved to sykehus. Pasienter med vedvarende dyspné etter PE diagnostisert 6 til 72 måneder tidligere, uten kardiopulmonale komorbiditeter, ble randomisert 1:1 til enten rehabiliterings- eller kontrollgruppen. Rehabiliteringsprogrammet besto av to ukentlige økter med fysisk trening i 8 uker og en pedagogisk økt. Kontrollgruppen fikk vanlig pleie. Det primære endepunktet var forskjellen i Incremental Shuttle Walk Test mellom grupper ved oppfølging. Sekundære endepunkter inkluderte forskjeller i Endurance Shuttle Walk Test (ESWT), QoL (EQ-5D og lungeemboli-QoL spørreskjemaer) og dyspné (Shortness of Breath spørreskjema). Resultater Totalt 211 forsøkspersoner ble inkludert: 108 (51 %) ble randomisert til rehabiliteringsgruppen og 103 (49 %) til kontrollgruppen. Ved oppfølging presterte deltakerne fordelt på rehabiliteringsgruppen bedre på ISWT sammenlignet med kontrollgruppen (gjennomsnittlig forskjell, 53,0 m; 95 % KI, 17,7-88,3; P = 0,0035). Rehabiliteringsgruppen rapporterte bedre skårer på spørreskjemaet lungeemboli-kvalitet (gjennomsnittlig forskjell, –4 %; 95 % KI, –0,09 til 0,00; P = 0,041) ved oppfølging, men det var ingen forskjeller i generisk livskvalitet, dyspné. score, eller ESWT. Ingen uønskede hendelser oppsto under intervensjonen. Tolkning Hos pasienter med vedvarende dyspné etter PE hadde de som gjennomgikk rehabilitering bedre treningskapasitet ved oppfølging enn de som fikk vanlig behandling. Rehabilitering bør vurderes hos pasienter med vedvarende dyspné etter PE. Ytterligere forskning er imidlertid nødvendig for å vurdere optimal pasientvalg, tidspunkt, modus og varighet av rehabilitering.publishedVersio

Detection of upper extremity deep vein thrombosis by magnetic resonance non-contrast thrombus imaging

Background Compression ultrasonography (CUS) is the first-line imaging test for diagnosing upper extremity deep vein thrombosis (UEDVT), but often yields inconclusive test results. Contrast venography is still considered the diagnostic standard but is an invasive technique. Objectives We aimed to determine the diagnostic accuracy of magnetic resonance noncontrast thrombus imaging (MR-NCTI) for the diagnosis of UEDVT. Methods In this international multicenter diagnostic study, we prospectively included patients with clinically suspected UEDVT who were managed according to a diagnostic algorithm that included a clinical decision rule (CDR), D-dimer test, and diagnostic imaging. UEDVT was confirmed by CUS or (computed tomography [CT]) venography. UEDVT was excluded by (1) an unlikely CDR and normal D-dimer, (2) a normal serial CUS or (3) a normal (CT) venography. Within 48 h after the final diagnosis was established, patients underwent MR-NCTI. MR-NCTI images were assessed post hoc by two independent radiologists unaware of the presence or absence of UEDVT. The sensitivity, specificity, and interobserver agreement of MR-NCTI for UEDVT were determined. Results Magnetic resonance noncontrast thrombus imaging demonstrated UEDVT in 28 of 30 patients with UEDVT and was normal in all 30 patients where UEDVT was ruled out, yielding a sensitivity of 93% (95% CI 78–99) and specificity of 100% (95% CI 88–100). The interobserver agreement of MR-NCTI had a kappa value of 0.83 (95% CI 0.69–0.97). Conclusions Magnetic resonance noncontrast thrombus imaging is an accurate and reproducible method for diagnosing UEDVT. Clinical outcome studies should determine whether MR-NCTI can replace venography as the second-line imaging test in case of inconclusive CUS