Measuring Quality of Life after Venous Thromboembolism: Who, When, and How?

There is a growing body of evidence revealing that many patients with a history of venous thromboembolism (VTE) suffer from long-lasting sequelae such as post-thrombotic syndrome and post-pulmonary embolism syndrome. These two syndromes are detrimental to patients as they affect their quality of life (QOL). From this perspective, monitoring QOL may play a crucial role to improve quality care in VTE patients. Many studies have explored possible temporal relations between VTE episodes and decreased functional status and/or QOL. However, studies exploring the implementation of QOL and functional status questionnaires in clinical practice are scarce. In this context, we discuss possible perspectives synthetized from available literature regarding in whom, when, and how QOL could be measured in clinical practice.

The mean bilateral proximal extension of the clot is associated with pulmonary embolism severity parameters and management-associated outcomes.

BACKGROUND: The value of the proximal extension of the clot in risk stratification of pulmonary embolism (PE) has not been established. The mean bilateral proximal extension of the clot (MBPEC) is a computed tomography (CT) radiological score, where initial evaluation showed promising results considering its ability in predicting the severity of PE. PURPOSE: To explore the possible associations between MBPEC and PE-severity parameters, short- and long-term outcomes of PE, and inter-observer agreement. MATERIAL AND METHODS: Patients diagnosed with PE at Østfold Hospital, Norway during 2003-2011 were identified. MBPEC was calculated by calculating the mean of a score in the range of 1-4 assigned for the most proximal extension of the clot in each lung: sub-segmental; segmental; lobar; and main pulmonary arteries. Medical records were reviewed to capture clinical, biochemical, and management-associated data (thrombolysis, admission to ICU). RESULTS: The mean age of 245 included patients was 55 ± 16 years; 42% were women. Patients with higher MBPEC scores had a significantly higher pulse rate and lower oxygen saturation. MBPEC score <4 predicted a negative troponin value with a negative predictive value of 90% (95% confidence interval [CI] 81-95). Patients with MBPEC 4 were 5.3 times more likely to have elevated troponin (odds ratio [OR] 5.3, 95% CI 2.0-14.3). MBPEC score of 4 was independently associated with admission to ICU (OR 3.8, 95% CI 1.8-7.9). The inter-observer agreement was excellent; weighted kappa 0.82. CONCLUSION: MBPEC is associated with PE-severity parameters and can predict short-term adverse outcomes.

Quality of life after pulmonary embolism: first cross-cultural evaluation of the pulmonary embolism quality-of-life (PEmb-QoL) questionnaire in a Norwegian cohort.

PURPOSE: The aim of the current study was to translate and test the psychometrical properties of the disease-specific pulmonary embolism quality-of-life questionnaire (PEmb-QoL). METHODS: Patients with a prior history of pulmonary embolism (PE) were identified from the thrombosis registry at Østfold Hospital Trust, Fredrikstad, Norway. All eligible patients were asked to complete the generic EuroQol 5-dimension (EQ-5D) QoL questionnaire as well as the disease-specific PEmb-QoL at baseline and after 2 weeks. Construct validity was tested using principal component factor analysis. Criterion validity was tested using Spearman's correlation coefficients (rho) between EQ-5D and PEmb-QoL. Internal consistency reliability was calculated using Cronbach's alpha coefficient, while test-retest reliability was calculated using the intra-class correlation coefficients (ICC). RESULTS: A total of 213 participants had complete datasets and were included in further analyses. Factor analysis with varimax rotation yielded six factors explaining 71% of the cumulative variance. Cronbach's alpha coefficient was found to be 0.94, indicating a very good intercorrelation of items. Of the 213 participants, 145 (68%) completed the questionnaire a second time. The ICC ranged from 0.75 to 0.86, indicating good test-retest reliability. All factors were found significant with p values <0.001. The criterion validity of the PEmb-QoL was confirmed through good correlation with other similar health-related quality-of-life constructs in the EQ-5D. CONCLUSIONS: Findings of the current study indicate that Norwegian version of the PEmb-QoL is both valid and reliable, thus representing an important supplement in subjective outcomes measurement among patients sustaining PE.

Incidence of venous thromboembolism, recurrence, and bleeding after isolated superficial vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital.

BACKGROUND: There are limited data on the long-term risk of venous thromboembolism (VTE) after high-risk isolated superficial vein thrombosis (iSVT) treated with anticoagulants. OBJECTIVES: To determine the short- and long-term risk of VTE and iSVT recurrence after cessation of anticoagulant treatment and to calculate 45-day cumulative bleeding incidence in patients with iSVT. METHODS: Between January 2014 and December 2021, 229 patients with high-risk iSVT (ie, thrombus length ≥5cm), without active cancer, with no history of VTE or iSVT, and who had received anticoagulant treatment for the iSVT were identified through the Venous Thrombosis Registry in Østfold Hospital (TROLL registry), Norway. Cumulative incidences of VTE and iSVT recurrence, as well as cumulative incidences of major and clinically relevant nonmajor bleeding events, were assessed. RESULTS: Median age was 60 years (IQR, 48-71), and 125 (55%) were women. Most patients were treated with direct oral anticoagulants (74%), and of these, 79% received a dose of rivaroxaban 10 mg daily. Low-molecular-weight heparin was given to 26% of the patients. The 1- and 5-year cumulative incidences of VTE after iSVT were 4.6% (95% CI, 2.5-8.3) and 15.9% (95% CI, 10.8-22.9), respectively. Further, the 1- and 5-year cumulative incidences of iSVT recurrence were 6.5% (95% CI, 3.9-10.7) and 15.9% (95% CI, 10.8-23.1), respectively. The overall 45-day cumulative incidence of major and clinically relevant nonmajor bleeding events was 0.4% (95% CI, 0.06-3.06) and 1.8% (95% CI, 0.7-4.6), respectively. No major bleeding events were observed in patients treated with direct oral anticoagulants. CONCLUSION: Despite anticoagulant treatment, the risk of VTE after high-risk iSVT was substantial, while bleeding complications were low.

Time Trends and Excess Mortality Compared to Population Controls after a First-Time Pulmonary Embolism or Deep Vein Thrombosis.

BACKGROUND: Recent data on temporal trends in excess mortality for patients with pulmonary embolism (PE) and deep vein thrombosis (DVT) compared with the general population are scarce. METHODS: A nationwide Swedish register study conducted from 2006 to 2018 including 68,960 PE and 70,949 DVT cases matched with population controls. Poisson regression determined relative risk (RR) for 30-day and 1-year mortality trends while Cox regression determined adjusted hazard ratios (aHRs). A significance level of 0.001 was applied. RESULTS: In PE cases, both 30-day mortality (12.5% in 2006 to 7.8% in 2018, RR: 0.95 [95% CI: 0.95-0.96], p < 0.0001) and 1-year mortality (26.5 to 22.1%, RR: 0.98 [0.97-0.98], p < 0.0001) decreased during the study period. Compared with controls, no significant change was seen in 30-day (aHR: 33.08 [95% CI: 25.12-43.55] to 24.64 [95% CI: 18.81-32.27], p = 0.0015 for interaction with calendar year) or 1-year (aHR: 5.85 [95% CI: 5.31-6.45] to 7.07 [95% CI: 6.43-7.78], p = 0.038) excess mortality. The 30-day excess mortality decreased significantly (aHR: 39.93 [95% CI: 28.47-56.00) to 24.63 [95% CI: 17.94-33.83], p = 0.0009) in patients with PE without known cancer before baseline, while the excess 1-year mortality increased (aHR: 3.55 [95% CI: 3.16-3.99] to 5.38 [95% CI: 4.85-5.98], p < 0.0001) in PE cases surviving to fill a prescription of anticoagulation. In DVT cases, 30-day and 1-year mortality declined, while excess mortality compared with controls remained stable. CONCLUSION: In general, the improved mortality following PE and DVT paralleled population trends. However, PE cases without cancer had decreasing excess 30-day mortality, whereas those surviving to fill a prescription for anticoagulant medication showed increasing excess 1-year mortality.

Physical activity following pulmonary embolism and clinical correlates in selected patients: a cross-sectional study.

Background: There is limited knowledge regarding physical activity and clinical correlates among people who have suffered a pulmonary embolism (PE). Objectives: To assess physical activity levels after PE and potential clinical correlates. Methods: One hundred forty-five individuals free of major comorbidities were recruited at a mean of 23 months (range, 6-72) after PE diagnosis. Physical activity was assessed by steps/day on the Sensewear monitor for 7 consecutive days, exercise capacity with the incremental shuttle walk test, and cardiac function with left ventricular ejection fraction (LVEF). The association between physical activity and other variables was analyzed by a mixed-effects model. Results: Participants achieved a mean of 6494 (SD, 3294; range, 1147-18.486) steps/day. The mixed-effects model showed that physical activity was significantly associated with exercise capacity (ß-coefficient, 0.04; 95% CI, 0.03-0.05) and LVEF (ß-coefficient, -0.81; 95% CI, -1.42 to -0.21). The analysis further showed that men became less physically active with increasing age (ß-coefficient, -0.14; 95% CI, -0.24 to -0.04), whereas no change with age could be detected for women. Conclusion: In selected post-PE patients, physical activity seems to be associated with exercise capacity and LVEF but not with quality of life, dyspnea, or characteristics of the initial PE. Men appear to become less physically active with increasing age.

Real-world Data on Treatment Patterns and Bleeding in Cancer-associated Thrombosis: Data from the TROLL Registry.

Background International guidelines are increasingly recommending direct oral anticoagulants (DOACs) as the first-line treatment for cancer-associated thrombosis (CAT). However, data regarding treatment patterns and adherence to guidelines in patients with CAT are scarce. Objectives This study aimed to explore anticoagulant treatment patterns in patients with CAT and to calculate the incidence rates of bleeding events. Methods Patients ≥18 years with active cancer and a first-time venous thromboembolism between 2005 and 2020 were identified through the Venous T hrombosis R egistry in Østf OL d Hospita L . Outcome measures were patterns of anticoagulant treatment during the study period and bleeding events. We calculated overall incidence rates per 100 person-years and 6- and 12-month cumulative incidence of major and clinically relevant nonmajor bleeding (CRNMB) during anticoagulant treatment. Results Median age of 842 CAT patients at the time of thrombosis was 69 years (interquartile range 61-77), and 443 (52.6%) were men. In total, 526 patients (62.5%) had pulmonary embolism and 255 (30.3%) had deep vein thrombosis. Low molecular weight heparin (LMWH) was prescribed to 713 (85.8%) patients, whereas 64 (7.7%) received DOACs and 54 (6.5%) received vitamin K antagonists as the initial anticoagulant treatment. Prescription of DOACs as initial treatment increased from 3.0% in 2013/2014 to 18.0% in 2019/2020. The incidence rate of major bleeding was 6.9 (95% confidence interval [CI] 5.2-9.2) and 10.1 (95% CI 8.0-12.9) in CRNMB. Conclusion Most patients were treated with LMWH. However, a gradual shift in treatment toward DOACs was observed. Overall, bleeding complications were rare and comparable to those reported in randomized trials.

Does the clot burden as assessed by the Mean Bilateral Proximal Extension of the Clot score reflect mortality and adverse outcome after pulmonary embolism?

Background: Rapid diagnosis and risk stratification are important to reduce the risk of adverse clinical events and mortality in acute pulmonary embolism (PE). Although clot burden has not been consistently shown to correlate with disease outcomes, proximally located PE is generally perceived as more severe. Purpose: To explore the ability of the Mean Bilateral Proximal Extension of the Clot (MBPEC) score to predict mortality and adverse outcome. Methods: This was a single center retrospective cohort study. 1743 patients with computed tomography pulmonary arteriography (CTPA) verified PE diagnosed between 2005 and 2020 were included. Patients with active malignancy were excluded. The PE clot burden was assessed with MBPEC score: The most proximal extension of PE was scored in each lung from 1 = sub-segmental to 4 = central. The MBPEC score is the score from each lung divided by two and rounded up to nearest integer. Results: We found inconsistent associations between higher and lower MBPEC scores versus mortality. The all-cause 30-day mortality of 3.9% (95% CI: 3.0-4.9). The PE-related mortality was 2.4% (95% CI: 1.7-3.3). Patients with MBPEC score 1 had higher all-cause mortality compared to patients with MBPEC score 4: Crude Hazard Ratio (cHR) was 2.02 (95% CI: 1.09-3.72). PE-related mortality was lower in patients with MBPEC score 3 compared to score 4: cHR 0.22 (95% CI: 0.05-0.93). Patients with MBPEC score 4 did more often receive systemic thrombolysis compared to patients with MBPEC score 1-3: 3.2% vs. 0.6% (p < .001). Patients with MBPEC score 4 where more often admitted to the intensive care unit: 13% vs. 4.7% (p < .001). Conclusion: We found no consistent association between the MBPEC score and mortality. Our results therefore indicate that peripheral PE does not necessarily entail a lower morality risk than proximal PE.

Incidence of bleeding and recurrence in isolated distal deep vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital.

BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is a common presentation of deep vein thrombosis. There are limited data on the long-term risk of recurrence after IDDVT. OBJECTIVES: We aimed to determine the short- and long-term incidence of venous thrombosis (VTE) recurrence after cessation of anticoagulation and the 3-month incidence of bleeding during anticoagulant treatment in patients with IDDVT. METHODS: Between January 2005 and May 2020, 475 patients with IDDVT and without active cancer were identified from the Venous Thrombosis Registry in Østfold Hospital, which is an ongoing registry of consecutive patients with VTE at Østfold Hospital, Norway. Major and clinically relevant, nonmajor bleeding as well as recurrent VTE were registered, and the cumulative incidences of these events were assessed. RESULTS: The median age of the patients was 59 years (IQR, 48-72 years), 243 (51%) patients were women, and 175 events (36.8%) were classified as unprovoked. The 1-, 5-, and 10-year cumulative incidences of recurrent VTE were 5.6% (95% CI, 3.7-8.4), 14.7% (95% CI, 11.1-19.4), and 27.2% (95% CI, 21.1-34.5), respectively. The recurrence rates were higher for unprovoked IDDVT than for provoked IDDVT. Among the recurrent events, 18 (29%) were pulmonary embolisms and 21 (33%) were proximal deep vein thromboses. The 3-month cumulative incidence of major bleeding was 1.5% (95% CI, 0.7-3.1) overall and 0.8% (95% CI, 0.2-3.1) when restricted to patients treated with direct oral anticoagulants. CONCLUSION: Despite initial treatment, the long-term risk of VTE recurrence after first-time IDDVT is high. The bleeding rates during anticoagulation, particularly with direct oral anticoagulants, were acceptably low.

Demographic, clinical, and echocardiographic factors associated with residual perfusion defects beyond six months after pulmonary embolism.

BACKGROUND: Residual perfusion defects (RPD) after pulmonary embolism (PE) are common. PRIMARY AIM: This study aimed to determine the prevalence of RPD in a cohort diagnosed with PE 6-72 months earlier, and to determine demographic, clinical, and echocardiographic variables associated with RPD. METHODS: Patients aged 18-75 years with prior PE, confirmed by computed tomography pulmonary angiography 6-72 months earlier, were included. Participants (N = 286) completed a diagnostic work-up consisting of transthoracic echocardiography and ventilation/perfusion scintigraphy. Demographic, clinical, and echocardiographic characteristics between participants with RPD and those without RPD were explored in univariate analyses using t-test or Mann-Whitney U test. Multiple logistic regression analysis was used to assess the association between selected variables and RPD. RESULTS: RPD were detected in 72/286 patients (25.2 %, 95 % CI:20.5 %-30.5 %). Greater tricuspid annular plane systolic excursion (TAPSE) (adjusted odds ratio (aOR) 1.10, 95 % CI:1.00-1.21, p = 0.048) at echocardiographic follow-up, greater thrombotic burden at diagnosis, as assessed by mean bilateral proximal extension of the clot (MBPEC) score 3-4 (aOR 2.08, 95 % CI:1.06-4.06, p = 0.032), and unprovoked PE (aOR 2.25, 95 % CI:1.13-4.48, p = 0.021) were independently associated with increased risk of RPD, whereas increased pulmonary artery acceleration time was associated with a lower risk of RPD (aOR 0.72, 95 % CI:0.62-0.83, p < 0.001, per 10 ms). Dyspnoea was not associated with RPD. CONCLUSION: RPD were common after PE. Reduced pulmonary artery acceleration time and greater TAPSE on echocardiography at follow-up, greater thrombotic burden at diagnosis, and unprovoked PE were associated with RPD.

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

BACKGROUND: Persistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the scientific evidence is limited. RESEARCH QUESTION: Does an exercise-based rehabilitation program improve exercise capacity in PE survivors with persistent dyspnea? STUDY DESIGN AND METHODS: This randomized controlled trial was conducted at two hospitals. Patients with persistent dyspnea following PE diagnosed 6 to 72 months earlier, without cardiopulmonary comorbidities, were randomized 1:1 to either the rehabilitation or the control group. The rehabilitation program consisted of two weekly sessions of physical exercise for 8 weeks and one educational session. The control group received usual care. The primary end point was the difference in Incremental Shuttle Walk Test between groups at follow-up. Secondary end points included differences in the Endurance Shuttle Walk Test (ESWT), QoL (EQ-5D and Pulmonary Embolism-QoL questionnaires) and dyspnea (Shortness of Breath questionnaire). RESULTS: A total of 211 subjects were included: 108 (51%) were randomized to the rehabilitation group and 103 (49%) to the control group. At follow-up, participants allocated to the rehabilitation group performed better on the ISWT compared with the control group (mean difference, 53.0 m; 95% CI, 17.7-88.3; P = .0035). The rehabilitation group reported better scores on the Pulmonary Embolism-QoL questionnaire (mean difference, -4%; 95% CI, -0.09 to 0.00; P = .041) at follow-up, but there were no differences in generic QoL, dyspnea scores, or the ESWT. No adverse events occurred during the intervention. INTERPRETATION: In patients with persistent dyspnea following PE, those who underwent rehabilitation had better exercise capacity at follow-up than those who received usual care. Rehabilitation should be considered in patients with persistent dyspnea following PE. Further research is needed, however, to assess the optimal patient selection, timing, mode, and duration of rehabilitation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03405480; URL: www. CLINICALTRIALS: gov.

The effect of rivaroxaban on the diagnostic value of D-dimer in patients with suspected deep vein thrombosis.

INTRODUCTION: Empiric anticoagulation therapy is often used in patients with suspected deep vein thrombosis (DVT) to avoid complications if the workup is delayed. Studies have shown the safety of administering direct oral anticoagulants (DOACs) and low molecular weight heparin in patients with suspected DVT. However, the impact of empiric DOACs on D-dimer levels in patients with suspected DVT is not well established. Therefore, this study aimed to determine the effect of empiric rivaroxaban on the diagnostic performance of D-dimer. MATERIALS AND METHODS: D-dimer was measured before and after the administration of one to two tablets of rivaroxaban in 418 patients referred with suspected DVT to the Emergency Department at Østfold Hospital, Norway. To determine whether the effect of rivaroxaban significantly impacted D-dimer results, we calculated the diagnostic performance of the test before and after patients had taken rivaroxaban. All patients with negative workup were followed up at 90 days. RESULTS: Two hundred eighty-six (68.4 %) of the 418 included patients had lower D-dimer results after taking rivaroxaban. Median D-dimer values decreased from 1.0 mg/L (IQR: 0.7-2.2) to 0.9 mg/L (IQR: 0.6-2.0). Thirty-six patients (8.9 %) with positive D-dimer (≥ 0.5 mg/L fibrinogen-equivalent units) before taking rivaroxaban had negative D-dimer values after rivaroxaban intake. Of these, two had DVT diagnosed by compression ultrasonography. The sensitivity of D-dimer decreased from 99.0 % (95 % CI: 94.6-99.8) to 97.0 % (95 % CI: 91.6-99.0). CONCLUSIONS: Rivaroxaban administered before measuring D-dimer may reduce the sensitivity and increase false negative results of the test. Based on these results, we recommend performing D-dimer before the administration of rivaroxaban.

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.

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.

Pulmonary and cardiac variables associated with persistent dyspnea after pulmonary embolism.

INTRODUCTION: Persistent dyspnea is common in follow-up after pulmonary embolism (PE), but the underlying mechanisms are poorly understood. MATERIAL AND METHODS: This cross-sectional study included subjects aged 18-75 years with confirmed PE by computed tomography pulmonary angiography (CTPA) 6-72 months earlier. A total of 180 participants underwent clinical examination, incremental shuttle walk test, laboratory tests, transthoracic echocardiography, pulmonary function tests and ventilation/perfusion scintigraphy. In further analysis, we divided participants into two groups; "dyspnea" or "no dyspnea", based on interview and questionnaires at inclusion. The association of cardiac and pulmonary variables with persistent dyspnea was assessed using multiple logistic regression analysis. RESULTS: In total, 44% (95% CI: 39%-51%) of the participants reported persistent dyspnea after PE. Age (adjusted odds ratio (aOR) 0.93 per year, 95% CI: 0.90-0.97, P = 0.001), body mass index (BMI) (aOR 1.14 per kg/m2, 95% CI: 1.04-1.25, P = 0.004), recurrent venous thromboembolism (VTE) (aOR 3.69, 95% CI: 1.45-9.38, P = 0.006) and diffusion capacity of the lung for carbon monoxide (DLCO) (aOR 0.95 per increase of 1%, 95% CI: 0.92-0.98, P = 0.001) were independently associated with persistent dyspnea. CONCLUSIONS: Persistent dyspnea was prevalent after PE. Age, BMI and recurrent VTE were independently associated with dyspnea. Apart from reduced DLCO, no other cardiac or pulmonary variables were associated with persistent dyspnea.

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.

BACKGROUND: Recently, a large group of patients with persistent dyspnea, poor physical capacity, and reduced health-related quality of life (HRQoL) following pulmonary embolism (PE) has been identified and clustered under the name "post pulmonary embolism syndrome" (PPS). These patients seem good candidates for pulmonary rehabilitation. The aim of the study is to explore whether a pulmonary rehabilitation program can improve physical capacity, dyspnea, and HRQoL in PPS patients. METHODS: A two-center randomized controlled trial (RCT) is being performed at Østfold Hospital and Akershus University Hospital in Norway. Patients with PPS are 1:1 randomized into an intervention or a control group. The intervention consists of a supervised, outpatient rehabilitation program twice weekly (1 h) for 8 weeks provided by experienced physiotherapists. The intervention involves individually adapted exercises based on existing pulmonary rehabilitation programs (relaxation, interval, and resistance training), and an educational session including topics such as normal anatomy and physiology of the respiratory and circulatory system, information on PE/PPS, breathing strategies, and benefits of exercise/physical activity. Patients randomized to the control group receive usual care without specific instructions to exercise. Participants in the intervention and control groups will be compared based on assessments conducted at baseline, 12 weeks, and 36 weeks after inclusion using the incremental shuttle walk test (primary outcome) and endurance shuttle walk test (exercise capacity), Sensewear activity monitor (daily physical activity), the modified Medical Research Council scale, the Shortness of Breath Questionnaire (dyspnea), and EQ-5D-5L and the Pulmonary Embolism Quality of Life Questionnaire (HRQoL). Recruitment of 190 patients is currently ongoing. DISCUSSION: Results from this study may provide a currently untreated group of PPS patients with an effective treatment resulting in reduced symptoms of dyspnea, improved exercise capacity, and better HRQoL following PE. TRIAL REGISTRATION: Clinical Trials NCT03405480 . Registered prospectively on September 2017. Protocol version 1 (from original protocol September 2017). The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 1).

Late consequences of venous thromboembolism: Measuring quality of life after deep vein thrombosis and pulmonary embolism.

The identification of specific post-thrombotic complications as well as an increased appreciation of the importance of patient-reported outcome measures have triggered an interest in studying health-related quality of life (HRQoL) in patients with a history of venous thromboembolism (VTE). In order to enable a comprehensive assessment of HRQoL in clinical trials it is recommended that both generic and disease-specific questionnaires be used. SF-36 and EQ-5D are the most widely used generic questionnaires in VTE studies, whereas several disease-specific questionnaires have been developed to evaluate HRQoL following deep vein thrombosis (DVT) and in chronic venous disease (CVD). The most widely used of these is the VEINES-QOL/Sym, which was developed for CVD. VT-QOL and DVTQOL are both questionnaires developed to evaluate HRQoL after DVT, while PEmb-QoL is currently the only available disease-specific questionnaire developed specifically for pulmonary embolism (PE). Although studies show inconsistent results, patients who sustain DVT seem in general to report similar HRQoL compared to the general population. However, patients who develop PTS after DVT report poorer HRQoL using both generic and disease-specific questionnaires. HRQoL appears to be impaired in patients who sustain PE compared to the general population. In these patients, persistent dyspnea after PE has been shown to be a predictor of reduced HRQoL. Further work is needed to develop practical, patient-derived, valid, reliable and responsive disease-specific HRQoL instruments covering the specific aspects of these diseases.

The impact of post-pulmonary embolism syndrome and its possible determinants.

INTRODUCTION: Recent studies suggest that up to 50% of patients surviving pulmonary embolism (PE) may suffer from post-PE syndrome, which is defined by persistent dyspnea, impaired exercise capacity and/or decreased health-related quality of life (HRQoL). The possible determinants of post-PE syndrome are however not fully established. AIMS: To describe the differences between dyspneic and non-dyspneic PE-patients and to explore determinants of dyspnea, 6-min walking test (6MWT) and HRQoL. MATERIAL AND METHODS: In this cross-sectional study, consecutive patients diagnosed with PE between 2002 and 2011 at Østfold Hospital, Norway were identified from hospital registries. Patients were scheduled for clinical examination and a 6MWT. Dyspnea was assessed by the New York Heart Association (NYHA) classification. HRQoL was assessed with PEmb-QoL questionnaire. PE severity was assessed with PESI score, mean bilateral proximal extent of the clot and right-/left ventricle-ratio (RV/LV-ratio). RESULTS: 203 patients participated in this study, of which 96 patients reported dyspnea (47%). Median time from diagnosis was 3.6 years (IQR 1.9-6.5). Patients without dyspnea performed better on 6MWT (488 m vs 413 m, p < 0.005) and had better HRQoL results (p < 0.005). None of the variables we examined, including Charlson comorbidity index, was independently associated with dyspnea. However, higher RV/LV ratio at diagnosis was significantly associated with reduced 6MWT at follow-up. Further, ongoing anticoagulation and unemployment were independently associated with impaired HRQoL. CONCLUSIONS: PE-survivors complaining of dyspnea suffer from impaired HRQoL and reduced exercise capacity. Although PE-severity factors were associated with reduced exercise capacity, none of the examined factors were found to be independent determinants of dyspnea.

Health-related quality of life after deep vein thrombosis.

BACKGROUND: Health-related quality of life (HRQoL) is known to be impaired in patients who develop post-thrombotic syndrome (PTS) following deep vein thrombosis (DVT). However, there is limited knowledge of the long-term HRQoL after DVT compared to controls without DVT. The objectives of this study were to evaluate long-term HRQoL following DVT and to compare that with age and sex matched control group and to population norms as well as to investigate possible predictors for reduced HRQoL. METHODS: HRQoL was evaluated in 254 patients with confirmed DVT using the generic EQ-5D and the diseases specific VEINES-QOL/Sym questionnaire, whereas PTS was assessed by the Villalta scale. Patients were asked to give the EQ-5D questionnaire to two friends of same age- (±5 years) and sex (buddy controls). RESULTS: Patients scored significantly lower on all dimensions of EQ-5D compared to controls. EQ-5D index value was lower in patients compared with buddy controls; mean 0.79 (SD 0.17; IQR 0.72-1.00) versus 0.9 (SD 0.12; IQR 0.80-1.00), p < 0.001. EQ-5D index value was also significantly lower than age- and sex-adjusted population norms (p < 0.001). PTS and obesity (BMI >30/m(2)) were significantly associated with impaired HRQoL assessed by EQ-5D index value (odds ratio [OR] 11.0: 95 % confidence interval [CI] 4.6-29.7; and 2.3: 95 % CI 1.1-4.8, respectively) and VEINES-QOL (OR 28.2: 95 % CI 10.6-75.0; and OR 4.1: 95 % CI 1.7-9.7, respectively). CONCLUSION: Long-term HRQoL was significantly impaired in DVT patients compared with buddy controls and population norms. PTS and obesity were independently associated with impaired HRQoL.

Health-related quality of life after pulmonary embolism: a cross-sectional study.

OBJECTIVES: The psychological effects of acute pulmonary embolism (PE) have scarcely been studied. The aims of this study were to evaluate health-related quality of life (HRQoL) in patients with a history of PE compared with that of the general population and buddy controls, and to explore factors that may predict impaired HRQoL. DESIGN: Cross-sectional. SETTING: Haematology and thrombosis unit in Fredrikstad, Norway. PARTICIPANTS: 213 consecutive patients treated for PE were identified from hospital registries. Eligible patients were scheduled for a single study visit, including a functional capacity test (6 min walking test). HRQoL was assessed using the EuroQol 5D dimensions 3-level (EQ-5D-3L) questionnaire, of which the results were compared with Danish population norms and age-matched and sex-matched buddy controls. The buddy controls were recruited by asking every patient to hand over the EQ-5D questionnaire to 2 age-matched and sex-matched friends or relatives. Multivariable regression analyses were used to examine possible determinants of reduced HRQoL. RESULTS: Mean age was 61 years (SD 15), 117 (55%) were males, and median time since diagnosis was 3.8 years (range 0.3-9.5). Mean EuroQol visual analogue scale (EQ VAS) was 67 in PE as compared with 81 in the general population (p<0.005) and corresponding EQ-5D index values were 0.80 and 0.86 (p<0.005). Patients reported more problems in all 5 EQ-5D compared with both the buddy controls and the general population, p<0.05. Shorter 6 min walking distance (ß=0.09, p<0.005) and patient-reported dyspnoea (ß=11.27, p<0.005) were independent predictors of lower EQ VAS scores. CONCLUSIONS: Our findings show that patients with a history of PE have impaired HRQoL when compared with the general population and buddy controls. Reduced functional capacity and persistent dyspnoea were the main predictors of this impairment.