Electrocardiographic abnormalities and NT-proBNP levels at long-term follow-up of patients with dyspnea after pulmonary embolism.

OBJECTIVES: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE. DESIGN: All Swedish patients diagnosed with acute PE in 2005 (n = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 (n = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration. RESULTS: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels. CONCLUSIONS: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

Pulmonary embolism in patients with chronic coronary syndrome masquerading as acute coronary syndrome: a case report and literature review.

BACKGROUND: Pulmonary embolisms (PEs) exhibit clinical features similar to those of acute coronary syndrome (ACS), including electrocardiographic abnormalities and elevated troponin levels, which frequently lead to misdiagnoses in emergency situations. CASE PRESENTATION: Here, we report a case of PE coinciding with chronic coronary syndrome in which the patient's condition was obscured by symptoms mimicking ACS. A 68-year-old female with syncope presented to the hospital. Upon admission, she was found to have elevated troponin levels and an electrocardiogram showing ST-segment changes across multiple leads, which initially led to a diagnosis of ACS. Emergency coronary arteriography revealed occlusion of the posterior branches of the left ventricle of the right coronary artery, but based on the complexity of the intervention, the occlusion was considered chronic rather than acute. On the 3rd day after admission, the patient experienced recurrent chest tightness and shortness of breath, which was confirmed as acute PE by emergency computed tomography pulmonary angiography. Following standardized anticoagulation treatment, the patient improved and was subsequently discharged. CONCLUSIONS: This case report highlights the importance of recognizing the nonspecific features of PE. Clinicians should be vigilant when identifying other clinical features that are difficult to explain accompanying the expected disease, and it is necessary to carefully identify the causes to prevent missed diagnoses or misdiagnoses.

Clinical usefulness of endothelial progenitor cells in predicting the efficacy of riociguat in chronic thromboembolic pulmonary hypertension.

Endothelial dysfunction is important in the pathology of pulmonary hypertension, and circulating endothelial progenitor cells (EPCs) have been studied to evaluate endothelial dysfunction. In patients with chronic thromboembolic pulmonary hypertension (CTEPH), riociguat reportedly increases the number of circulating EPCs. However, the relationship between EPC numbers at baseline and changes in clinical parameters after riociguat administration has not been fully elucidated. Here, we evaluated 27 treatment-naïve patients with CTEPH and analyzed the relationships between EPC number at diagnosis and clinical variables (age, hemodynamics, atrial blood gas parameters, brain natriuretic peptide, and exercise tolerance) before and after riociguat initiation. EPCs were defined as CD45dim CD34+ CD133+ cells and measured by flow cytometry. A low number of circulating EPCs at diagnosis was significantly correlated with increased reductions in mean pulmonary arterial pressure (mPAP) (correlation coefficient = 0.535, P = 0.004) and right atrial pressure (correlation coefficient = 0.618, P = 0.001) upon riociguat treatment. We then divided the study population into two groups according to the mPAP change: a weak-response group (a decrease in mPAP of 4 mmHg or less) and a strong-response group (a decrease in mPAP of more than 4 mmHg). The number of EPCs at diagnosis was significantly lower in the strong-response group than in the weak-response group (P = 0.022), but there were no significant differences in other clinical variables or in medication profiles. In conclusion, circulating EPC numbers could be a potential predictor of the therapeutic effect of riociguat in CTEPH patients.

Association between severity of pulmonary embolism and health-related quality of life.

Background: Health-related quality of life (QoL) impairment is common after pulmonary embolism (PE). Whether the severity of the initial PE has an impact on QoL is unknown. Objectives: To evaluate the association between severity of PE and QoL over time. Methods: We prospectively assessed PE-specific QoL using the Pulmonary Embolism Quality of Life (lower scores indicate better QoL) questionnaire and generic QoL using the Short Form 36 (higher scores indicate better QoL) questionnaire at baseline and 3 and 12 months in older patients with acute PE. We examined whether QoL differed by PE severity based on hemodynamic status, simplified Pulmonary Embolism Severity Index (sPESI), right ventricular function, and high-sensitivity troponin T in mixed-effects models, adjusting for known QoL predictors after PE. Results: Among 546 patients with PE (median age, 74 years), severe vs nonsevere PE based on the sPESI was associated with a worse PE-specific (adjusted mean Pulmonary Embolism Quality of Life score difference of 6.1 [95% CI, 2.4-9.8] at baseline, 7.6 [95% CI, 4.0-11.3] at 3 months, and 6.7 [95% CI, 2.9-10.4] at 12 months) and physical generic QoL (adjusted mean Short Form 36 Physical Component Summary score difference of -3.8 [95% CI, -5.5 to -2.1] at baseline, -4.8 [95% CI, -6.4 to -3.1] at 3 months, and -4.1 [95% CI, -5.8 to -2.3] at 12 months). Elevated troponin levels were also associated with lower PE-specific QoL at 3 months and lower physical generic QoL at 3 and 12 months. QoL did not differ by hemodynamic status or right ventricular function. Conclusion: Severe PE based on the sPESI was consistently associated with worse PE-specific and physical generic QoL over time as compared to nonsevere PE.

Lemierre Syndrome: Clinical Challenges And The Anticoagulation Dilemma In Adolescent Care.

Lemierre syndrome is a rare, life-threatening condition characterized by an acute otorhinolaryngologic infection with septic thrombophlebitis of the internal jugular vein and septic embolism, particularly to the lungs. We describe a case of a previously healthy 15-year-old female patient who initially presents fever and odynophagia but quickly develops neck and pleuritic chest pain. Computed tomography was performed and the radiological findings confirmed the diagnosis of a Lemierre syndrome. She was managed with antibiotics, anticoagulant for three days and symptomatic treatment, with a gradually improving condition. After 17 days of hospitalisation, due to reappearance of pleuritic pain, a new imaging assessment was performed and showed additional septic emboli in the lungs, which prompted the reintroduction of anticoagulant therapy. Awareness of the existence of this syndrome is essential to ensure a radiological evaluation with computed tomography and thus timely diagnosis and treatment.

Medication adherence, related factors and outcomes among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: a systematic review.

INTRODUCTION: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening conditions that can progress to death without treatment. Although strong medication adherence (MA) is known to enhance outcomes in chronic illnesses, its association with PAH and CTEPH was sporadically explored. This study aims to examine the MA of patients with PAH or CTEPH, identify factors associated with low adherence and explore the resulting outcomes. METHODS: A systematic review was conducted by searching multiple databases (Medline, Embase, Cochrane Central, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar) from 6 March 1998 to 6 July 2023. We included studies reporting MA as primary or secondary end-points. Study selection, data extraction and methodological quality assessment were performed in duplicate. RESULTS: 20 studies involving 22 675 patients met the inclusion criteria. Heterogeneity was observed, particularly in the methods employed. MA means ranged from 0.62 to 0.96, with the proportion of patients exhibiting high MA varying from 40% (95% CI 35-45%) to 94% (95% CI 88-97%). Factors associated with low adherence included increased treatment frequency, time since diagnosis and co-payment. High MA seems to be associated with reduced hospitalisation rates, inpatient stays, outpatient visits and healthcare costs. CONCLUSIONS: This systematic review underscores the heterogeneity of MA across studies. Nevertheless, the findings suggest that high MA could improve patients' clinical outcomes and alleviate the economic burden. Identifying factors consistently associated with poor MA could strengthen educational efforts for these patients, ultimately contributing to improved outcomes.

The prevalence, risk factors, and outcomes of acute pulmonary embolism complicating sepsis and septic shock: a national inpatient sample analysis.

The study aimed to evaluate the prevalence, risk factors, and clinical outcomes of pulmonary embolism in patients diagnosed with sepsis with and without shock. The National Inpatient Sample was used to identify adults with sepsis with and without shock between 2017 and 2019. The prevalence of acute pulmonary embolism and the association of acute pulmonary embolism with in-hospital mortality, hospital length of stay for survivors, and overall costs of hospitalization were evaluated. Multivariable logistic and linear regression analyses, adjusted for various parameters, were used to explore these associations. Of the estimated 5,019,369 sepsis hospitalizations, 1.2% of patients with sepsis without shock and 2.3% of patients with septic shock developed pulmonary embolism. The odds ratio for in-hospital mortality was 1.94 (95% confidence interval (CI) 1.85-2.03, p < 0.001). The coefficient for hospital length of stay was 3.24 (95% CI 3.03-3.45, p < 0.001). The coefficient for total costs was 46,513 (95% CI 43,079-49,947, p < 0.001). The prevalence of pulmonary embolism in patients diagnosed with sepsis with and without shock was 1.2 and 2.3%, respectively. Acute pulmonary embolism was associated with higher in-hospital mortality, longer hospital length of stay for survivors, and higher overall costs of hospitalization.

Pulmonary Embolism in Klippel-Trenaunay-Weber Syndrome With Slipped Capital Femoral Epiphysis.

CASE: A 12-year-old boy with Klippel-Trenaunay-Weber syndrome underwent surgery for unstable slipped capital femoral epiphysis who developed pulmonary embolism postoperatively. CONCLUSION: It is important to be vigilant about pulmonary embolism in children because it is rare but potentially fatal, especially in the presence of risk factors. Early diagnosis and treatment of unstable slipped capital femoral epiphysis are crucial to minimize immobility. Close monitoring of femoral head osteonecrosis is also necessary.

Isolated Calf Muscle Venous Thrombosis: A Review of Anticoagulation Strategies.

Deep vein thrombosis (DVT) of the lower extremities is divided into 2 categories according to the extent of thrombosis involvement. Thrombosis involving the popliteal vein, femoral vein, and iliac vein is classified as proximal DVT, while thrombosis involving the anterior tibial vein, posterior tibial vein, peroneal vein, and calf muscles vein is regarded as distal DVT. There are updated guidelines for the anticoagulant treatment for proximal DVT, but the best anticoagulant treatment for distal DVT is still controversial, especially for isolated calf muscular vein thrombosis (CMVT). The risk of isolated CMVT extending to the proximal deep veins and developing into pulmonary embolism is lower than with distal DVT. Some scholars believe that isolated CMVT has the risk of evolving into proximal deep vein thrombosis and pulmonary embolism, and active early anticoagulation therapy can reduce the risk and benefit patients. In addition, based on the characteristics of CMVT and the bleeding risk of anticoagulation therapy, some studies have recommended use of non-anticoagulation methods such as compression therapy. There is still a lack of multicenter, big-data, randomized, controlled trials on the benefits or risks of anticoagulation therapy. Among scholars who support anticoagulation therapy, there is still a lack of consensus on the optimal duration. This article reviews the current evidence on anticoagulant therapy for patients with isolated CMVT and how long the anticoagulation course should be if anticoagulation is required. Our research will provide a theoretical basis for subsequent research. More prospective studies with larger sample sizes are needed to provide more clinical evidence.

Cardiopulmonary Complications after Pulmonary Embolism in COVID-19.

Although pulmonary embolism (PE) is a frequent complication in COVID-19, its consequences remain unknown. We performed pulmonary function tests, echocardiography and computed tomography pulmonary angiography and identified blood biomarkers in a cohort of consecutive hospitalized COVID-19 patients with pneumonia to describe and compare medium-term outcomes according to the presence of PE, as well as to explore their potential predictors. A total of 141 patients (56 with PE) were followed up during a median of 6 months. Post-COVID-19 radiological lung abnormalities (PCRLA) and impaired diffusing capacity for carbon monoxide (DLCOc) were found in 55.2% and 67.6% cases, respectively. A total of 7.3% had PE, and 6.7% presented an intermediate-high probability of pulmonary hypertension. No significant difference was found between PE and non-PE patients. Univariate analysis showed that age > 65, some clinical severity factors, surfactant protein-D, baseline C-reactive protein, and both peak red cell distribution width and Interleukin (IL)-10 were associated with DLCOc < 80%. A score for PCRLA prediction including age > 65, minimum lymphocyte count, and IL-1ß concentration on admission was constructed with excellent overall performance. In conclusion, reduced DLCOc and PCRLA were common in COVID-19 patients after hospital discharge, but PE did not increase the risk. A PCRLA predictive score was developed, which needs further validation.

Decreased Thrombin Generation is Associated with Increased Thrombin Generation Biomarkers and Blood Cellular Indices in Pulmonary Embolism.

Pulmonary embolism (PE) is a heterogenous condition with variable clinical presentations. Thrombin generation potential (TGP) and biomarkers, and blood cellular indices can reflect the underlying pathophysiology and risk stratification of PE. This case-control study analyzed TGP in 209 PE patients from Loyola University, Pulmonary Embolism Response Team program compared to normal human plasma (NHP) controls. The present study evaluates TGP and biomarkers, and cellular indices in relation to PE severity, according to the European Society of Cardiology (ESC) guidelines. Statistical analysis including median with interquartile range (IQR), 2-tailed Wilcoxon Mann-Whitney test, Chi-square test, and Spearman Correlational analysis were performed. There were 209 patients with PE, with an almost equal distribution between sex, and a median age of 63 years. Significant downregulation in peak thrombin and endogenous thrombin potential (ETP), as well as upregulation in lag time, were observed in PE patients versus controls. Biomarker analysis revealed pronounced elevations, with D-dimer demonstrating the most significant increase. Blood cellular indices also rose in PE patients, correlating with disease severity. PE severity was associated with higher TGP and biomarker levels. Mortality rates differed significantly across risk categories and were highest in patients with elevated cellular indices. TGP and biomarkers are intricately linked to PE severity and can aid in risk stratification. Elevated cellular indices are associated with increased mortality, highlighting their potential as prognostic markers. These findings could enhance the precision of PE management strategies.

Mechanical chest compressions as a last-ditch attempt to salvage a profoundly hypoxic but normotensive patient with a massive pulmonary embolism.

Massive pulmonary embolism is a common cause of morbidity and mortality. For patients presenting with massive pulmonary embolism, severe hypoxia is usually associated with severe hypotension. These patients should be considered for thrombectomy should thrombolysis and respiratory support fail to improve their condition. Should thrombectomy not be available or suitable, consideration should be given to offering mechanical chest compressions to 'break up the clot'. We describe a case in which this seemingly led to survival and full recovery.

Multidisciplinary Approach to Pulmonary Embolism and the Role of the Pulmonary Embolism Response Team.

PURPOSE OF REVIEW: Acute pulmonary embolism (PE) is a leading cause of cardiovascular death and morbidity, and presents a major burden to healthcare systems. The field has seen rapid growth with development of innovative clot reduction technologies, as well as ongoing multicenter trials that may completely revolutionize care of PE patients. However, current paucity of robust clinical trials and guidelines often leave individual physicians managing patients with acute PE in a dilemma. RECENT FINDINGS: The pulmonary embolism response team (PERT) was developed as a platform to rapidly engage multiple specialists to deliver evidence-based, organized and efficient care and help address some of the gaps in knowledge. Several centers investigating outcomes following implementation of PERT have demonstrated shorter hospital and intensive-care unit stays, lower use of inferior vena cava filters, and in some instances improved mortality. Since the advent of PERT, early findings demonstrate promise with improved outcomes after implementation of PERT. Incorporation of artificial intelligence (AI) into PERT has also shown promise with more streamlined care and reducing response times. Further clinical trials are needed to examine the impact of PERT model on care delivery and clinical outcomes.

nnU-Net-based deep-learning for pulmonary embolism: detection, clot volume quantification, and severity correlation in the RSPECT dataset.

OBJECTIVES: CT pulmonary angiography is the gold standard for diagnosing pulmonary embolism, and DL algorithms are being developed to manage the increase in demand. The nnU-Net is a new auto-adaptive DL framework that minimizes manual tuning, making it easier to develop effective algorithms for medical imaging even without specific expertise. This study assesses the performance of a locally developed nnU-Net algorithm on the RSPECT dataset for PE detection, clot volume measurement, and correlation with right ventricle overload. MATERIALS & METHODS: User input was limited to segmentation using 3DSlicer. We worked with the RSPECT dataset and trained an algorithm from 205 PE and 340 negatives. The test dataset comprised 6573 exams. Performance was tested against PE characteristics, such as central, non-central, and RV overload. Blood clot volume (BCV) was extracted from each exam. We employed ROC curves and logistic regression for statistical validation. RESULTS: Negative studies had a median BCV of 1 µL, which increased to 345 µL in PE-positive cases and 7,378 µL in central PEs. Statistical analysis confirmed a significant BCV correlation with PE presence, central PE, and increased RV/LV ratio (p < 0.0001). The model's AUC for PE detection was 0.865, with an 83 % accuracy at a 55 µL threshold. Central PE detection AUC was 0.937 with 91 % accuracy at 850 µL. The RV overload AUC stood at 0.848 with 79 % accuracy. CONCLUSION: The nnU-Net algorithm demonstrated accurate PE detection, particularly for central PE. BCV is an accurate metric for automated severity stratification and case prioritization. CLINICAL RELEVANCE STATEMENT: The nnU-Net framework can be utilized to create a dependable DL for detecting PE. It offers a user-friendly approach to those lacking expertise in AI and rapidly extracts the Blood Clot Volume, a metric that can evaluate the PE's severity.

Identifying pulmonary embolism - high risk patients after total knee replacement: systematic review.

OBJECTIVE: To determine the incidence, onset, risk factors and mortality of pulmonary embolism in total knee replacement patients. METHODS: The systematic review was conducted in September 2022, and comprised search on PubMed, ScienceDirect, Scopus and Crossref databases for studies published from 1977 till September 7, 2022, in the English language related to the incidence of pulmonary embolism after primary total knee replacement. Cochrane Handbook for Systematic Reviews of Interventions was used to assess risk of bias, and the Newcastle-Ottawa Scale was used to assess the quality of evidence. RESULTS: Of the 3,910 studies initially identified, 66(1.68%) were analysed in detail, which together had 13,258,455 total knee replacement patients. Pulmonary embolism was reported in 76,515(0.58%) cases. The onset of pulmonary embolism ranged 2-150 days post-surgery. Patients with older age, diabetes mellitus, higher body mass index, atrial fibrillation, previous venous thromboembolism, high Charlson Comorbidity Index score, hypertension, arrhythmia and chronic heart failure were at significantly higher risk (p<0.05). The overall mortality rate of pulmonary embolism in such cases ranged 10.53-100%. CONCLUSIONS: Pulmonary embolism is a rare complication after orthopaedic surgery, but it has a very high mortality rate. By recognising the risk factors, attending physicians can optimise the use of chemoprophylaxis, thus preventing pulmonary embolism.

[Effects of pulmonary embolism response team on the quality of care and clinical outcomes in patients with acute pulmonary embolism].

Objective: To evaluate the effects of pulmonary embolism response team (PERT) on the quality of care and clinical outcomes in patients with acute pulmonary embolism. Methods: This was a single-center retrospective cohort study. Patients with acute pulmonary embolism treated in Beijing Anzhen Hospital Affiliated to Capital Medical University from July 5, 2016 to July 4, 2018 were enrolled. Patients with acute pulmonary embolism who had traditional care from July 5, 2016 to July 4, 2017 (before the implementation of PERT) were classified as PERT pre-intervention group. Patients with acute pulmonary embolism who started PERT care from July 5, 2017 to July 4, 2018 were divided into the PERT intervention group. The diagnosis and treatment information of patients was collected through the electronic medical record system, and the quality of care (time from visit to hospitalization, time from hospitalization to anticoagulation initiation, time from visit to definitive diagnosis, total hospital stay, time in intensive care unit (ICU), hospitalization cost) and clinical outcomes (in-hospital mortality and incidence of bleeding) were compared between the two groups. Results: A total of 210 patients with acute pulmonary embolism, aged (63.3±13.7) years old, with 102 (48.6%) female patients were included. There were 108 cases in PERT pre-intervention group and 102 cases in PERT intervention group. (1) Quality of diagnosis and treatment: there was a statistical significance between the two groups in the distribution of time from diagnosis to definitive diagnosis (P=0.002). Among them, the rate of completion of diagnosis within 24 hours after PERT intervention was higher than that before PERT intervention (80.4% (45/56) vs. 50.0% (34/68), P<0.001). The time from treatment to hospitalization was shorter than that before PERT intervention (180.0 (60.0, 645.0) min vs. 900.0 (298.0, 1 806.5) min, P<0.001). The total length of hospital stay was less than that before PERT intervention (12 (10, 14) d vs. 14 (11, 16) d, P=0.001). There was no statistical significance in the time from hospitalization to anticoagulant therapy, the length of ICU stay and hospitalization cost between the two groups (all P>0.05). (2) Clinical outcomes during hospitalization: There was no statistical significance in the incidence of hemorrhage and mortality between the two groups during hospitalization (both P>0.05). Conclusion: PERT has improved the efficiency of diagnosis and treatment of patients with acute pulmonary embolism and significantly shortened the total hospital stay, but its impact on clinical outcomes still needs further study.

At-admission prediction of mortality and pulmonary embolism in an international cohort of hospitalised patients with COVID-19 using statistical and machine learning methods.

By September 2022, more than 600 million cases of SARS-CoV-2 infection have been reported globally, resulting in over 6.5 million deaths. COVID-19 mortality risk estimators are often, however, developed with small unrepresentative samples and with methodological limitations. It is highly important to develop predictive tools for pulmonary embolism (PE) in COVID-19 patients as one of the most severe preventable complications of COVID-19. Early recognition can help provide life-saving targeted anti-coagulation therapy right at admission. Using a dataset of more than 800,000 COVID-19 patients from an international cohort, we propose a cost-sensitive gradient-boosted machine learning model that predicts occurrence of PE and death at admission. Logistic regression, Cox proportional hazards models, and Shapley values were used to identify key predictors for PE and death. Our prediction model had a test AUROC of 75.9% and 74.2%, and sensitivities of 67.5% and 72.7% for PE and all-cause mortality respectively on a highly diverse and held-out test set. The PE prediction model was also evaluated on patients in UK and Spain separately with test results of 74.5% AUROC, 63.5% sensitivity and 78.9% AUROC, 95.7% sensitivity. Age, sex, region of admission, comorbidities (chronic cardiac and pulmonary disease, dementia, diabetes, hypertension, cancer, obesity, smoking), and symptoms (any, confusion, chest pain, fatigue, headache, fever, muscle or joint pain, shortness of breath) were the most important clinical predictors at admission. Age, overall presence of symptoms, shortness of breath, and hypertension were found to be key predictors for PE using our extreme gradient boosted model. This analysis based on the, until now, largest global dataset for this set of problems can inform hospital prioritisation policy and guide long term clinical research and decision-making for COVID-19 patients globally. Our machine learning model developed from an international cohort can serve to better regulate hospital risk prioritisation of at-risk patients.