Estimated Annual Healthcare Costs After Acute Pulmonary Embolism: Results From a Prospective Multicentre Cohort Study.

OBJECTIVE: Patients surviving acute pulmonary embolism (PE) necessitate long-term treatment and follow-up. However, the chronic economic impact of PE on European healthcare systems remains to be determined. METHODS AND RESULTS: We calculated the direct cost of illness during the first year after discharge for the index PE, analyzing data from a multicentre prospective cohort study in Germany. Main and accompanying readmission diagnoses were used to calculate DRG-based hospital reimbursements; anticoagulation costs were estimated from the exact treatment duration and each drug's unique national identifier; and outpatient post-PE care costs from guidelines-recommended algorithms and national reimbursement catalogues. Of 1017 patients enrolled at 17 centres, 958 (94%) completed ≥ 3-month follow-up; of those, 24% were rehospitalized (0.34 [95% CI 0.30-0.39] readmissions per PE survivor). Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis of 837 patients with complete 12-month follow-up) cancer, but not recurrent PE, were independent cost predictors by hurdle gamma regression accounting for zero readmissions. Estimated rehospitalization cost was €1138 (95% CI 896-1420) per patient. Anticoagulation duration was 329 (IQR 142-365) days, with estimated average per-patient costs of €1050 (median 972; IQR 458-1197); costs of scheduled ambulatory follow-up visits amounted to €181. Total estimated direct per-patient costs during the first year after PE ranged from €2369 (primary analysis) to €2542 (sensitivity analysis). CONCLUSIONS: By estimating per-patient costs and identifying cost drivers of post-PE care, our study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved cardiovascular prevention. (Trial registration number: DRKS00005939).

Optimisation of detecting chronic thromboembolic pulmonary hypertension in acute pulmonary embolism survivors: the InShape IV study.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed late in acute pulmonary embolism (PE) survivors: more efficient testing to expedite diagnosis may considerably improve patient outcomes. The InShape II algorithm safely rules out CTEPH (failure rate 0.29%) while requiring echocardiography in only 19% of patients but may be improved by adding detailed reading of the computed tomography pulmonary angiography (CTPA) diagnosing the index PE. METHODS: Twelve new algorithms, incorporating the CTEPH prediction score, ECG reading, NT-proBNP levels and dedicated CTPA reading were evaluated in the international InShape II (n=341) and part of the German FOCUS cohort (n=171). Evaluation criteria included failure rate, defined as the incidence of confirmed CTEPH in PE patients in whom echocardiography was deemed unnecessary by the algorithm, and the overall net reclassification index (NRI) compared to the InShape II algorithm. RESULTS: The algorithm starting with CTPA reading of the index PE for 6 signs of CTEPH, followed by the ECG/NTproBNP assessment and echocardiography resulted in the most beneficial change compared to InShape II with a need for echocardiography in 20% (+5%), a failure rate of 0%, and an NRI of +3.5, reflecting improved performance over the InShape II algorithm. In the FOCUS cohort, this approach lowered echocardiography need to 24% (-6%) and missed no CTEPH cases, with an NRI of +6.0. CONCLUSION: Dedicated CTPA reading of the index PE improved the performance of the InShape II algorithm and may improve the selection of PE survivors who require echocardiography to rule out CTEPH.

Extracorporeal Membrane Oxygenation and Reperfusion Strategies in High-Risk Pulmonary Embolism Hospitalizations.

OBJECTIVES: To investigate the contemporary use of extracorporeal membrane oxygenation (ECMO) in conjunction with reperfusion strategies in high-risk pulmonary embolism (PE). DESIGN: Observational epidemiological analysis. SETTING: The U.S. Nationwide Inpatient Sample (NIS) (years 2016-2020). PATIENTS: High-risk PE hospitalizations. MEASUREMENTS AND MAIN RESULTS: Use of ECMO in conjunction with thrombolysis-based reperfusion (systemic thrombolysis or catheter-directed thrombolysis) or mechanical reperfusion (surgical embolectomy or catheter-based thrombectomy) with regards to in-hospital mortality and major bleeding. We identified high-risk PE hospitalizations in the NIS (years 2016-2020) and investigated the use of ECMO in conjunction with thrombolysis-based (systemic thrombolysis or catheter-directed thrombolysis) and mechanical (surgical embolectomy or catheter-based thrombectomy) reperfusion strategies with regards to in-hospital mortality and major bleeding. Among 122,735 hospitalizations for high-risk PE, ECMO was used in 2,805 (2.3%); stand-alone in 1.4%, thrombolysis-based reperfusion in 0.4%, and mechanical reperfusion in 0.5%. Compared with neither reperfusion nor ECMO, ECMO plus thrombolysis-based reperfusion was associated with reduced in-hospital mortality (adjusted odds ratio [aOR] 0.61; 95% CI, 0.38-0.98), whereas no difference was found with ECMO plus mechanical reperfusion (aOR 1.03; 95% CI, 0.67-1.60), and ECMO stand-alone was associated with increased in-hospital mortality (aOR 1.60; 95% CI, 1.22-2.10). In the cardiac arrest subgroup, ECMO was associated with reduced in-hospital mortality (aOR 0.71; 95% CI, 0.53-0.93). Among all patients on ECMO, thrombolysis-based reperfusion was significantly associated (aOR 0.55; 95% CI, 0.33-0.91), and mechanical reperfusion showed a trend (aOR 0.75; 95% CI, 0.47-1.19) toward reduced in-hospital mortality compared with no reperfusion, without increases in major bleeding. CONCLUSIONS: In patients with high-risk PE and refractory hemodynamic instability, ECMO may be a valuable supportive treatment in conjunction with reperfusion treatment but not as a stand-alone treatment especially for patients suffering from cardiac arrest.

Lipid lowering for prevention of venous thromboembolism: a network meta-analysis.

BACKGROUND AND AIMS: Studies have suggested that statins may be associated with reduced risk of venous thromboembolism (VTE). The aim of the current study was to assess the evidence regarding the comparative effect of all lipid-lowering therapies (LLT) in primary VTE prevention. METHODS: After a systematic search of PubMed, CENTRAL, and Web of Science up until 2 November 2022, randomized controlled trials (RCT) of statins (high- or low-/moderate-intensity), ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were selected. An additive component network meta-analysis to compare VTE risk during long-term follow-up across different combinations of LLT was performed. RESULTS: Forty-five RCTs (n = 254 933 patients) were identified, reporting a total of 2084 VTE events. Compared with placebo, the combination of PCSK9i with high-intensity statin was associated with the largest reduction in VTE risk (risk ratio [RR] 0.59; 95% confidence interval [CI] 0.43-0.80), while there was a trend towards reduction for high-intensity (0.84; 0.70-1.02) and low-/moderate-intensity (0.89; 0.79-1.00) statin monotherapy. Ezetimibe monotherapy did not affect the VTE risk (1.04; 0.83-1.30). There was a gradual increase in the summary effect of VTE reduction with increasing intensity of the LLT. When compared with low-/moderate-intensity statin monotherapy, the combination of PCSK9i and high-intensity statin was significantly more likely to reduce VTE risk (0.66; 0.49-0.89). CONCLUSIONS: The present meta-analysis of RCTs suggests that LLT may have a potential for VTE prevention, particularly in high-intensity dosing and in combination therapy.

Unmet needs and barriers in venous thromboembolism education and awareness among people living with cancer: a global survey.

BACKGROUND: Venous thromboembolism (VTE) is a major preventable cause of morbidity, disability, and mortality in subjects with cancer. A global appraisal of cancer-associated VTE education and awareness is not available. OBJECTIVES: To evaluate VTE-related education, awareness, and unmet needs from the perspective of people living with cancer using a quantitative and qualitative approach. METHODS: This cross-sectional study used data from an online-based survey covering multidimensional domains of cancer-associated VTE. Data are presented descriptively. Potential differences across participant subgroups were explored. RESULTS: Among 2262 patients with cancer from 42 countries worldwide, 55.3% received no VTE education throughout their cancer journey, and an additional 8.2% received education at the time of VTE diagnosis only, leading to 63.5% receiving no or inappropriately delayed education. When education was delivered, only 67.8% received instructions to seek medical attention in case of VTE suspicion, and 36.9% reported scarce understanding. One-third of participants (32.4%) felt psychologically distressed when becoming aware of the potential risks and implications connected with cancer-associated VTE. Most responders (78.8%) deemed VTE awareness highly relevant, but almost half expressed concerns about the quality of education received. While overall consistent, findings in selected survey domains appeared to numerically differ across age group, ethnicity, continent of residence, educational level, metastatic status, and VTE history. CONCLUSION: This study involving a large and diverse population of individuals living with cancer identifies important unmet needs in VTE-related education, awareness, and support across healthcare systems globally. These findings unveil multilevel opportunities to expedite patient-centered care in cancer-associated VTE prevention and management.

Mortality trend of ischemic heart disease (2008-2022): A retrospective analysis of epidemiological data.

BACKGROUND: Age-sex specific trend analyses of ischemic heart disease (IHD)-related mortality and prevalent risk factors can improve our understanding and approach to the disease. METHODS: We performed a 15-year retrospective epidemiological analysis of acute and chronic IHD-related mortality and prevalent cardiovascular risk factors using administrative data from Veneto, a socio-economically homogeneous Italian region. Standard mortality statistics using the underlying cause of death (UCOD) and deaths with any mention of IHD in death certificates (MCOD) from ICD-10 codes I20-I25 was performed between 2008 and 2022. RESULTS: A total of 134,327 death certificates reported IHD-related deaths, representing 18.6% of all deaths. Proportional mortality decreased from 14.6% in 2008 to 7.8% in 2022 for deaths with IHD as the UCOD and from 23.5% to 14.6% for deaths with IHD among the MCOD. A more pronounced decline of proportionate and case-specific mortality rate was seen in women. The decline in mortality over the whole study period was larger for acute (vs. chronic) IHD. The COVID-19 pandemic led to a marked increase in mortality in 2020 (+12.2%) with a subsequent further decline. IHD-related deaths displayed a typical seasonal pattern with more deaths during winter. The prevalence of cardiovascular risk factors was higher in IHD (vs. no IHD) deaths: this association appeared more pronounced in younger adults. CONCLUSIONS: We provided an analysis of epidemiological trends in IHD-related mortality and prevalence of risk factors. Our findings indicate a change in the pattern of cardiovascular deaths and may suggest a switch in death from acute to chronic conditions.

Drivers and recent trends of hospitalisation costs related to acute pulmonary embolism.

BACKGROUND AND AIMS: The socio-economic burden imposed by acute pulmonary embolism (PE) on European healthcare systems is largely unknown. We sought to determine temporal trends and identify cost drivers of hospitalisation for PE in Germany. METHODS AND RESULTS: We analysed the totality of reimbursed hospitalisation costs in Germany (G-DRG system) in the years 2016-2020. Overall, 484 884 PE hospitalisations were coded in this period. Direct hospital costs amounted to a median of 3572 (IQR, 2804 to 5869) euros, resulting in average total reimbursements of 710 million euros annually. Age, PE severity, comorbidities and in-hospital (particularly bleeding) complications were identified by multivariable logistic regression as significant cost drivers. Use of catheter-directed therapy (CDT) constantly increased (annual change in the absolute proportion of hospitalisations with CDT + 0.40% [95% CI + 0.32% to + 0.47%]; P < 0.001), and it more than doubled in the group of patients with severe PE (28% of the entire population) over time. Although CDT use was overall associated with increased hospitalisation costs, this association was no longer present (adjusted OR 1.02 [0.80-1.31]) in patients with severe PE and shock; this was related, at least in part, to a reduction in the median length of hospital stay (for 14.0 to 8.0 days). CONCLUSIONS: We identified current and emerging cost drivers of hospitalisation for PE, focusing on severe disease and intermediate/high risk of an adverse early outcome. The present study may inform reimbursement decisions by policymakers and help to guide future health economic analysis of advanced treatment options for patients with PE.

Modelling costs of interventional pulmonary embolism treatment: implications of US trends for a European healthcare system.

AIMS: Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the USA in the past decade, but the potential economic impact on European healthcare systems remains unknown. METHODS AND RESULTS: We built two statistical models for the monthly trend of proportion of CDT among patients with severe (intermediate- or high-risk) PE in the USA. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-20 and the model reflecting increasing access to advanced treatment from the PERT™ national quality assurance database registry 2018-21. By applying these models to the forecast of annual PE-related hospitalizations in Germany, we calculated the annual number of severe PE cases and the expected increase in CDT use for the period 2025-30. The NIS-based model yielded a slow increase, reaching 3.1% (95% confidence interval 3.0-3.2%) among all hospitalizations with PE in 2030; in the PERT-based model, increase would be steeper, reaching 8.7% (8.3-9.2%). Based on current reimbursement rates, we estimated an increase of annual costs for PE-related hospitalizations in Germany ranging from 15.3 to 49.8 million euros by 2030. This calculation does not account for potential cost savings, including those from reduced length of hospital stay. CONCLUSION: Our approach and results, which may be adapted to other European healthcare systems, provide a benchmark for healthcare costs expected to result from CDT. Data from ongoing trials on clinical benefits and cost savings are needed to determine cost-effectiveness and inform reimbursement decisions.

Healthcare resource utilisation and associated costs after low-risk pulmonary embolism: pre-specified analysis of the Home Treatment of Pulmonary Embolism (HoT-PE) study.

BACKGROUND: Pulmonary embolism (PE) and its sequelae impact healthcare systems globally. Low-risk PE patients can be managed with early discharge strategies leading to cost savings, but post-discharge costs are undetermined. PURPOSE: To define healthcare resource utilisation and overall costs during follow-up of low-risk PE. METHODS: We used an incidence-based, bottom-up approach and calculated direct and indirect costs over 3-month follow-up after low-risk PE, with data from the Home Treatment of Patients with Low-Risk Pulmonary Embolism (HoT-PE) cohort study. RESULTS: Average 3-month costs per patient having suffered low-risk PE were 7029.62 €; of this amount, 4872.93 € were associated with PE, accounting to 69.3% of total costs. Specifically, direct costs totalled 3019.33 €, and of those, 862.64 € (28.6%) were associated with PE. Anticoagulation (279.00 €), rehospitalisations (296.83 €), and ambulatory visits (194.95 €) comprised the majority of the 3-month direct costs. The remaining costs amounting to 4010.29 € were indirect costs due to loss of productivity. CONCLUSION: In a patient cohort with acute low-risk PE followed over 3 months, the majority of costs were indirect costs related to productivity loss, whereas direct, PE-specific post-discharge costs were low. Effective interventions are needed to reduce the burden of PE and associated costs, especially those related to productivity loss.

Functional capacity and dyspnea during follow-up after acute pulmonary embolism.

BACKGROUND: Dissecting the determinants of functional capacity during long-term follow-up after acute pulmonary embolism (PE) can help to better characterize a patient population with persisting limitation. METHODS: In a prospective cohort study, consecutive unselected survivors of acute PE underwent 3- and 12-month follow-up, including six-minute walking distance (6MWD) and dyspnea assessment with the modified Medical Research Council (mMRC) scale. We used reference equations adjusting for age, sex, and anthropometric measurements to define abnormal 6MWD. RESULTS: Overall, 323 of 363 (89.0%) patients had at least one recorded 6MWD value at one year. At 3 months, the prevalence of abnormal 6MWD was 21.9% and at 12 months it was 18.3%. At 3 and 12 months, 58.8% and 52.1% with abnormal 6MWD did not report dyspnea, respectively. On average and during follow-up, 6MWD significantly improved with time, while the mMRC dyspnea scale did not. Abnormal 6MWD was associated with younger age (odds ratio per decade, 0.91; 95% CI, 0.88-0.94), higher body mass index (1.10; 1.03-1.17), smoking (3.53; 1.34-9.31), intermediate- or high-risk PE (3.21; 1.21-8.56), and higher mMRC grading (2.28; 1.59-3.27). Abnormal 6MWD at 3 months was associated with the prospectively defined endpoint of post-PE impairment (3.72; 1.50-9.28) and with poor disease-specific and generic health-related quality of life. CONCLUSION: Three months after PE, 37% of patients reported dyspnea and 22% had abnormal 6MWD. After a year, 20% still had abnormal 6MWD. Dyspnea correlated with abnormal 6MWD, but over 50% of patients with abnormal 6MWD did not report dyspnea. Abnormal 6MWD predicted subsequent post-pulmonary embolism impairment and worse long-term quality of life. CLINICAL TRIAL REGISTRATION: German Clinical Trials Register Identifier DRKS00005939.

A nationwide analysis of reperfusion therapies for pulmonary embolism in older patients with frailty.

BACKGROUND: Reperfusion therapy is challenging in the elderly. Catheter-directed therapies are an alternative for higher-risk pulmonary embolism (PE) patients if systemic thrombolysis (ST) is contraindicated or has failed. Their safety has not been evaluated in specific vulnerable populations. AIMS: We aimed to assess the safety of reperfusion therapies in elderly and frail patients in the real world. METHODS: In the US Nationwide Inpatient Sample from 2016 to 2020, we identified hospitalisations of patients ≥65 years with PE and defined a frailty subgroup using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. We investigated reperfusion therapies (ST, catheter-directed thrombolysis [CDT], catheter-based thrombectomy [CBT], surgical embolectomy [SE]) and their associated safety outcomes (overall and major bleeding). RESULTS: Among 980,245 hospitalisations of patients ≥65 years with PE (28.0% frail), reperfusion therapies were used in 4.9% (17.6% among high-risk PE). ST utilisation remained stable, while the use of catheter-directed therapies increased from 1.7% in 2016 to 3.2% in 2020. Among all hospitalisations with reperfusion, CDT, compared to ST, was associated with reduced major bleeding (5.8% vs 12.2%, odds ratio [OR] 0.58, 95% confidence interval [CI]: 0.49-0.70); these results also applied to frail patients. CBT, compared to SE, was also associated with reduced major bleeding (11.0% vs 22.4%, OR 0.63, 95% CI: 0.43-0.91), but not among frail patients. These differences were particularly significant in patients with non-high-risk PE. Differences persisted for overall bleeding as well. CONCLUSIONS: Catheter-directed therapies may be a safer alternative to classical reperfusion therapies for elderly and frail patients with PE requiring reperfusion treatment.

Common laboratory tests and their correlation with the clinical presentation and prognosis of Lemierre syndrome.

INTRODUCTION: Lemierre syndrome is a thromboembolic complication following an acute bacterial infection of the head/neck area, often due to anaerobes. Data on the prognostic role of laboratory parameters is lacking. METHODS: We analyzed individual-patient level data from a multinational cohort of patients with Lemierre-syndrome. Patients had an infection in the head/neck area, and contiguous vein thrombosis or septic embolism, irrespective of the causal pathogen. We studied the patterns of white blood cell count, platelet count, and C-reactive protein concentration investigating their association with baseline characteristics and in-hospital clinical outcomes (septic embolism, major bleeding, all-cause death). RESULTS: A total of 447 (63%) patients had complete data for analysis. White blood cells were elevated across all subgroups (median 17 × 103/µL; Q1-Q3:12-21). Median platelet count was 61 × 103/µL (Q1-Q3:30-108) with decreasing levels with increasing age. Males, patients with renal failure or cardiopulmonary impairment, and those with typical Lemierre syndrome (tonsillitis, septic thromboembolism, positivity for Fusobacterium spp.) had the lowest platelet count. Median C-reactive protein was 122 (Q1-Q3:27-248) mg/L with higher values in patients who also had more severe thrombocytopenia. The overall risk of complications was similar across subgroups of patients stratified according to white blood cell and C-reactive protein levels. Patients in the lowest third of platelet count (<42 × 103/µL) had the highest rate of complications (26%), as opposed to those in the highest third (11%), notably septic embolic events. CONCLUSIONS: Common laboratory tests correlate with the clinical presentation of Lemierre syndrome. However, extreme values did not appear to be prognostically relevant for in-hospital complications and potentially able to improve clinical management.

Social determinants of health in pulmonary embolism management and outcome in hospitals: Insights from the United States nationwide inpatient sample.

Background: The role of social determinants in the treatment and course of acute pulmonary embolism (PE) is understudied. Objective: To investigate the association between social determinants of health with in-hospital management and early clinical outcomes following acute PE. Methods: We identified hospitalizations of adults with acute PE discharge diagnosis from the nationwide inpatient sample (2016-2018). Multivariable regression was used to investigate the association between race/ethnicity, type of expected primary payer, and income with the use of advanced PE therapies (thrombolysis, catheter-directed treatment, surgical embolectomy, extracorporeal membrane oxygenation), length of stay, hospitalization charges, and in-hospital death. Results: A total of 1,124,204 hospitalizations with a PE diagnosis were estimated from the 2016-2018 nationwide inpatient sample, corresponding to a hospitalization rate of 14.9/10,000 adult persons-year. The use of advanced therapies was lower in Black and Asian/Pacific Islander (vs. White patients: adjusted odds ratio [ORadjusted], 0.87; 95% confidence interval [CI], 0.81-0.92 and ORadjusted 0.76; 95% CI, 0.59-0.98) and in Medicare- or Medicaid-insured (vs. privately-insured; ORadjusted, 0.73; 95% CI, 0.69-0.77 and ORadjusted, 0.68; 95% CI, 0.63-0.74), although they had the greatest length of stay and hospitalization charges. In-hospital mortality was higher in the lowest income quartile (vs. highest quartile; ORadjusted, 1.09; 95% CI, 1.02-1.17). Among high-risk PE, patients of other than the White race had the highest in-hospital mortality. Conclusion: We observed inequalities in advanced therapies used for acute PE and higher in-hospital mortality in races other than White. Low socioeconomic status was also associated with lesser use of advanced treatment modalities and greater in-hospital mortality. Future studies should further explore and consider the long-term impact of social inequities in PE management.

Impact of venous thromboembolism on incidence of arterial thromboembolism - An analysis of German outpatient claims data.

BACKGROUND: Venous thromboembolism (VTE) and arterial thromboembolism (ATE) are considered as two separate disease-entities. In recent years, studies have reported clear associations between VTE and atherosclerosis. We aimed to evaluate the long-term risk of ATE in VTE patients in comparison to controls without VTE. METHODS: Nationwide outpatient claims data of all inhabitants with statutory health insurance in Germany were used for secondary data analysis between the years 2011 and 2020. Patients treated in 2013 were stratified by VTE event, and groups were 1:2-matched by age and sex. The hazard for an ATE event in a 5-year follow-up period between patients with and without VTE was calculated with multivariable Cox regression adjusted for age, sex, cardiovascular risk factors, and comorbidities. RESULTS: Of 69,699,277 individuals treated in the year 2013 by German physicians in outpatient care, in total 686,382 individuals (age 59.8 ± 17.5 years, 65.4 % females) were included comprising 228,794 patients with VTE and 457,588 controls without VTE. VTE patients more often had cardiovascular risk factors (81.6 % vs. 62.2 %) and traditional VTE risk factors. The occurrence of ATE events during follow-up was 1.8 %-points higher in VTE patients in comparison to the controls (9.7 % vs. 7.9 %). VTE events were independently associated with increased occurrence of ATE events within follow-up (HRadjusted 1.19 [99%CI 1.16-1.23], p < 0.0001). CONCLUSIONS: Patients with a VTE event have an increased long-term risk for subsequent arterial cardiovascular events. Large prospective cohorts are needed to identify patient subgroups with a very high ATE risk after VTE.

Cardiopulmonary exercise testing during follow-up after acute pulmonary embolism.

BACKGROUND: Cardiopulmonary exercise testing (CPET) may provide prognostically valuable information during follow-up after pulmonary embolism (PE). Our objective was to investigate the association of patterns and degree of exercise limitation, as assessed by CPET, with clinical, echocardiographic and laboratory abnormalities and quality of life (QoL) after PE. METHODS: In a prospective cohort study of unselected consecutive all-comers with PE, survivors of the index acute event underwent 3- and 12-month follow-ups, including CPET. We defined cardiopulmonary limitation as ventilatory inefficiency or insufficient cardiocirculatory reserve. Deconditioning was defined as peak O2 uptake (V'O2 ) <80% with no other abnormality. RESULTS: Overall, 396 patients were included. At 3 months, prevalence of cardiopulmonary limitation and deconditioning was 50.1% (34.7% mild/moderate; 15.4% severe) and 12.1%, respectively; at 12 months, it was 44.8% (29.1% mild/moderate; 15.7% severe) and 14.9%, respectively. Cardiopulmonary limitation and its severity were associated with age (OR per decade 2.05, 95% CI 1.65-2.55), history of chronic lung disease (OR 2.72, 95% CI 1.06-6.97), smoking (OR 5.87, 95% CI 2.44-14.15) and intermediate- or high-risk acute PE (OR 4.36, 95% CI 1.92-9.94). Severe cardiopulmonary limitation at 3 months was associated with the prospectively defined, combined clinical-haemodynamic end-point of "post-PE impairment" (OR 6.40, 95% CI 2.35-18.45) and with poor disease-specific and generic health-related QoL. CONCLUSIONS: Abnormal exercise capacity of cardiopulmonary origin is frequent after PE, being associated with clinical and haemodynamic impairment as well as long-term QoL reduction. CPET can be considered for selected patients with persisting symptoms after acute PE to identify candidates for closer follow-up and possible therapeutic interventions.

Predisposing factors for admission to intensive care units of patients with COVID-19 infection-Results of the German nationwide inpatient sample.

Background: Intensive care units (ICU) capacities are one of the most critical determinants in health-care management of the COVID-19 pandemic. Therefore, we aimed to analyze the ICU-admission and case-fatality rate as well as characteristics and outcomes of patient admitted to ICU in order to identify predictors and associated conditions for worsening and case-fatality in this critical ill patient-group. Methods: We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19 diagnosis in Germany between January and December 2020. All hospitalized patients with confirmed COVID-19 infection during the year 2020 were included in the present study and were stratified according ICU-admission. Results: Overall, 176,137 hospitalizations of patients with COVID-19-infection (52.3% males; 53.6% aged ≥70 years) were reported in Germany during 2020. Among them, 27,053 (15.4%) were treated in ICU. COVID-19-patients treated on ICU were younger [70.0 (interquartile range (IQR) 59.0-79.0) vs. 72.0 (IQR 55.0-82.0) years, P < 0.001], more often males (66.3 vs. 48.8%, P < 0.001), had more frequently cardiovascular diseases (CVD) and cardiovascular risk-factors with increased in-hospital case-fatality (38.4 vs. 14.2%, P < 0.001). ICU-admission was independently associated with in-hospital death [OR 5.49 (95% CI 5.30-5.68), P < 0.001]. Male sex [OR 1.96 (95% CI 1.90-2.01), P < 0.001], obesity [OR 2.20 (95% CI 2.10-2.31), P < 0.001], diabetes mellitus [OR 1.48 (95% CI 1.44-1.53), P < 0.001], atrial fibrillation/flutter [OR 1.57 (95% CI 1.51-1.62), P < 0.001], and heart failure [OR 1.72 (95% CI 1.66-1.78), P < 0.001] were independently associated with ICU-admission. Conclusion: During 2020, 15.4% of the hospitalized COVID-19-patients were treated on ICUs with high case-fatality. Male sex, CVD and cardiovascular risk-factors were independent risk-factors for ICU admission.

Mortality rate related to peripheral arterial disease: A retrospective analysis of epidemiological data (years 2008-2019).

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is one of the most prevalent cardiovascular diseases with more than 230 million people being affected worldwide. As highlighted by the recent European Society of Cardiology guidelines, data on the epidemiology of PAD is urgently needed. METHODS AND RESULTS: We accessed the vital registration data of the Veneto region (Northern Italy, approximately five millions inhabitants) covering the period 2008-2019. We computed annual age-standardized rates for PAD reported as the underlying cause of death (UCOD) or as one of multiple causes of death (MCOD). Age-adjusted odds ratios (OR) served to study the association between PAD and cardiovascular comorbidities. The age-standardized mortality rate for PAD as MCOD slightly declined from 19.6 to 17.8 in men and from 10.8 to 9.1 deaths per 100,000 population-years in women. The age-standardized PAD-specific mortality rate (UCOD) remained stable: 3.1 to 3.7 per 100,000 person-years in women (Average Annual Percent Change 1.3, 95% CI -0.8; 3.4%) and 4.4 to 4.3 per 100,000 person-years (Average Annual Percent Change -0.2, 95% CI -3.6; 3.4%) in men. PAD contributed to 1.6% of all deaths recorded in the region. Ischemic heart disease, diabetes mellitus and neoplasms were the most prevalent UCOD among PAD patients. PAD was associated with diabetes mellitus (OR 3.79, 95%CI 3.55-4.06) and chronic kidney diseases (OR 2.73, 95%CI 2.51-2.97) in men, and with atrial fibrillation (OR 2.26, 95%CI 2.10-2.44) in women. CONCLUSION: PAD remains a substantial cause of death in the general population of this high-income region of Western Europe with marked sex-specific differences.

Preexisting Chronic Thromboembolic Pulmonary Hypertension in Acute Pulmonary Embolism.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is considered a complication of pulmonary embolism (PE). However, signs of CTEPH may exist in patients with a first symptomatic PE. RESEARCH QUESTION: Which radiologic findings on CT pulmonary angiography (CTPA) at the time of acute PE could indicate the presence of preexisting CTEPH? STUDY DESIGN AND METHODS: This study included unselected patients with acute PE who were prospectively followed up for 2 years with a structured visit schedule. Two expert radiologists independently assessed patients' baseline CTPAs for preexisting CTEPH; in case of disagreement, a decision was reached by a 2:1 majority with a third expert radiologist. In addition, the radiologists checked for predefined individual parameters suggesting chronic PE and pulmonary hypertension. RESULTS: Signs of chronic PE or CTEPH at baseline were identified in 46 of 303 included patients (15%). Intravascular webs, arterial narrowing or retraction, dilated bronchial arteries, and right ventricular hypertrophy were the main drivers of the assessment. Five (1.7%) patients were diagnosed with CTEPH during follow-up. All four patients diagnosed with CTEPH early (83-108 days following acute PE) were found in enriched subgroups based on the experts' overall assessment or fulfilling a minimum number of the predefined radiologic criteria at baseline. The specificity of preexisting CTEPH diagnosis and the level of radiologists' agreement improved as the number of required criteria increased. INTERPRETATION: Searching for predefined radiologic parameters suggesting preexisting CTEPH at the time of acute PE diagnosis may allow for targeted follow-up strategies and risk-adapted CTEPH screening, thus facilitating earlier CTEPH diagnosis.

Risk of venous thromboembolic events after COVID-19 infection: a systematic review and meta-analysis.

Data regarding the occurrence of venous thromboembolic events (VTE), including acute pulmonary embolism (PE) and deep vein thrombosis (DVT) in recovered COVID-19 patients are scant. We performed a systematic review and meta-analysis to assess the risk of acute PE and DVT in COVID-19 recovered subject. Following the PRIMSA guidelines, we searched Medline and Scopus to locate all articles published up to September 1st, 2022, reporting the risk of acute PE and/or DVT in patients recovered from COVID-19 infection compared to non-infected patients who developed VTE over the same follow-up period. PE and DVT risk were evaluated using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins I2 statistic. Overall, 29.078.950 patients (mean age 50.2 years, 63.9% males), of which 2.060.496 had COVID-19 infection, were included. Over a mean follow-up of 8.5 months, the cumulative incidence of PE and DVT in COVID-19 recovered patients were 1.2% (95% CI:0.9-1.4, I2: 99.8%) and 2.3% (95% CI:1.7-3.0, I2: 99.7%), respectively. Recovered COVID-19 patients presented a higher risk of incident PE (HR: 3.16, 95% CI: 2.63-3.79, I2 = 90.1%) and DVT (HR: 2.55, 95% CI: 2.09-3.11, I2: 92.6%) compared to non-infected patients from the general population over the same follow-up period. Meta-regression showed a higher risk of PE and DVT with age and with female gender, and lower risk with longer follow-up. Recovered COVID-19 patients have a higher risk of VTE events, which increase with aging and among females.