BackgroundPersistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the... Show moreBackgroundPersistent 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 QuestionDoes an exercise-based rehabilitation program improve exercise capacity in PE survivors with persistent dyspnea?Study Design and MethodsThis 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).ResultsA 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.InterpretationIn 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. Show less
Gleditsch, J.; Jervan, O.; Klok, F.; Holst, R.; Hopp, E.; Tavoly, M.; Ghanima, W. 2023
BackgroundRapid 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... Show moreBackgroundRapid 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.PurposeTo explore the ability of the Mean Bilateral Proximal Extension of the Clot (MBPEC) score to predict mortality and adverse outcome.MethodsThis 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.ResultsWe 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).ConclusionWe 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. Show less
Jervan, O.; Dhayyat, A.; Gleditsch, J.; Haukeland-Parker, S.; Tavoly, M.; Klok, F.A.; ... ; Steine, K. 2023
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... Show moreBackground: 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. Show less
Gleditsch, J.; Jervan, O.; Haukeland-Parker, S.; Tavoly, M.; Geier, O.; Holst, R.; ... ; Hopp, E. 2022
Background: Persistent dyspnea and reduced exercise capacity is common in pulmonary embolism (PE) survivors. Although improved right ventricular function after pulmonary rehabilitation has been... Show moreBackground: 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. Show less
Gleditsch, J.; Jervan, O.; Tavoly, M.; Geier, O.; Holst, R.; Klok, F.A.; ... ; Hopp, E. 2022
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... Show moreBackground: 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. Show less
Jervan, O.; Gleditsch, J.; Tavoly, M.; Klok, F.A.; Rashid, D.; Holst, R.; ... ; Ghanima, W. 2021
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... Show moreIntroduction: 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. Show less
BackgroundRecently, 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... Show moreBackgroundRecently, 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.MethodsA two-center randomized controlled trial (RCT) is being performed at Ostfold 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 (1h) for 8weeks 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, 12weeks, and 36weeks 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.DiscussionResults 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 registrationClinical 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). Show less
Tavoly, M.; Wik, H.S.; Sirnes, P.A.; Jelsness-Jorgensen, L.P.; Ghanima, J.P.; Klok, F.A.; ... ; Ghanima, W. 2018
