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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.Which radiologic findings on computed tomography pulmonary angiography (CTPA) at the time of acute PE could indicate the presence of a pre-existing CTEPH?We included unselected patients with acute PE who were prospectively followed for 2 years with a structured visit schedule. Two expert radiologists independently assessed patients' baseline CTPAs for pre-existing CTEPH; in case of disagreement, a decision was reached by 2:1 majority with a third expert. In addition, the radiologists checked for predefined individual parameters suggesting chronic PE and pulmonary hypertension. Signs of chronic PE or CTEPH at baseline were identified in 46 (15%) of 303 included patients. 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 after acute PE) could be 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 pre-existing CTEPH diagnosis and the level of radiologists' agreement improved as the number of required criteria increased.Searching for predefined radiologic parameters suggesting pre-existing 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.

Introduction The occurrence of obstructive sleep apnea (OSA) is strongly associated with obesity. Behavioral, pharmacological, and surgical interventions that promote weight reduction can reduce OSA severity and improve other common obesity related complications and quality of life. While the relationship between weight reduction and apnea-hypopnea index (AHI) improvement has been documented, it does not seem to have been quantified adequately. The objective of this analysis was to quantify the association between percent change in body weight and percent change in AHI using results from the literature. Methods A literature search identified 13 studies with AHI and weight measurements before and after weight intervention in people living with obesity and OSA; 6 studies from bariatric surgery, 4 studies from diet and exercise intervention, and 3 studies from anti-obesity medications (including 2 placebo-controlled randomized clinical trials). A polynomial and a linear meta regression model as well as 95% prediction intervals were used to assess the relationship between % weight change from baseline and % change in AHI from baseline. Results Both the polynomial and linear models show, on average, weight reduction in patients living with obesity and OSA has a clinical benefit in reducing AHI. The linear meta-regression model that we developed suggests a mean AHI decrease of 2.6% per 1% weight reduction. As the prediction intervals are relatively wide, a precise relationship could not be established. For example, based on the linear model for a patient with 20% weight reduction we expect to see a mean 52.8% reduction in AHI with a 95% prediction interval (89.8%, 15.8%) AHI reduction. Conclusion Evidence shows that intentional weight reduction in people living with obesity and OSA results in improvements in OSA severity, and this was confirmed by our meta-analysis and modeling. The model shows that the degree of AHI improvement is dependent on the magnitude of weight reduction. However, establishing a precise relationship between percent change in AHI and percent weight reduction is challenging given the sparsity of data, variability in populations studied, and variability in AHI change following weight reduction. Support (if any) Eli Lilly and Company

Introduction Weight reduction is a standard recommended component of OSA treatment in people with obesity or overweight; however, the challenge to achieve and maintain weight reduction has limited its clinical application outside of the benefit established after bariatric surgery. Currently no FDA-approved anti-obesity medication (AOM) has demonstrated clinically meaningful improvement in OSA severity and symptomology. Methods Tirzepatide is a single molecule GIP and GLP-1 receptor agonist. In SURMOUNT-1, a 72-week phase 3 clinical trial in participants with obesity or overweight, tirzepatide 15mg provided average reductions in body weight of 22.5% which occurred with beneficial effects on blood pressure, lipids, and physical functioning. In a linear meta regression model, we estimated that tirzepatide treatment would provide clinically meaningful apnea-hypopnea index decrease compared to placebo-treated participants with obesity and OSA. SURMOUNT-OSA, a placebo controlled 52-week, phase 3 trial, will investigate efficacy and safety of tirzepatide for the treatment of moderate to severe OSA (defined as AHI ≥15) in participants with obesity. SURMOUNT-OSA utilizes an umbrella master protocol and 2 Intervention-Specific Appendices (ISAs): ISA 1 includes participants with no current OSA treatment and ISA 2 includes participants using positive airway pressure therapy. Approximately 412 participants will be randomly assigned to placebo or tirzepatide across the entire master protocol, with approximately 206 participants in each ISA. While participants will receive tirzepatide or placebo based on a 1:1 randomization ratio, all participants will receive background lifestyle intervention for weight reduction. Results The primary endpoint for the individual ISAs is the difference in AHI response measured by polysomnography between tirzepatide and placebo arms at week 52. Secondary endpoints include hypoxic burden, functional outcomes and cardiometabolic biomarkers. The trial is utilizing a unique hierarchical functional outcomes endpoint based on Functional Outcomes of Sleep Questionnaire methodology. The trial employs wearables, such as home sleep testing and accelerometry to capture time to improvement as exploratory outcomes. Conclusion SURMOUNT-OSA aims to explore whether tirzepatide provides clinically meaningful improvement in obesity-related OSA by targeting an underlying etiology. Support (if any) Eli Lilly

Dilated cardiomyopathy (DCM), an incurable disease of the cardiomyocyte terminating in systolic heart failure (HFrEF), is prevalent, causes hospitalization and is associated with increased mortality. Despite evidence of immune activation in DCM, anti-inflammatory interventions so far did not prove to alter the course of this disease. Here we show that myeloperoxidase (MPO), the principal heme peroxidase expressed by polymorphonuclear neutrophils (PMN) and monocytes, critically contributes to HFrEF in DCM.Muscle LIM protein (MLP) deficient mice, which spontaneously develop DCM, display increased circulating PMN counts and augmented levels of vessel-immobilized MPO. Genetic ablation and pharmacological inhibition of MPO resulted in enhanced nitric oxide (NO) bioavailability of systemic conductance and resistance vessels, and subsequently restoration of systolic left ventricular (LV) function, whereas infusion of MPO worsened systolic LV function. When patients diagnosed for DCM were treated with an orally available MPO inhibitor, systolic LV function increased, natriuretic peptides declined, and functional status improved.Impairment of endothelial NO bioavailability by release of leukocyte-derived MPO evolves as a disease-aggravating mechanism in DCM. MPO inhibition profoundly improved ventricular function by lowering systemic vascular resistance and thus holds promise as a novel and complementary treatment strategy for patients with DCM.

Background/Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be a late complication of acute pulmonary embolism (PE). However, up to one third of CTEPH patients do not report prior symptomatic venous thromboembolism (VTE). Furthermore, a substantial proportion of patients presenting with an acute PE event may exhibit radiological signs of chronicity at baseline computed tomography pulmonary angiography (CTPA). Purpose To determine the prevalence of baseline radiological parameters indicating chronic thrombosis or pulmonary hypertension, and ultimately pre-existing CTEPH, among patients with acute PE enrolled in the prospective multicentre Follow-Up after Acute Pulmonary Embolism (FOCUS) cohort study. Methods Patients with acute symptomatic PE and absence of a known history of CTEPH, enrolled at two large FOCUS centres, were included. The assessment of index CTPA scans was conducted by two independent expert radiologists who were unaware of the clinical characteristics and the follow-up data of the patients. CTPA parameters indicating chronicity were prespecified on the basis of recently proposed criteria in the literature. A third independent expert radiologist provided an assessment in case of disagreement between the first two. Baseline radiological data were prospectively validated with the aid of two-year prospective clinical follow-up data focusing on CTEPH and the post-PE syndrome (co-primary outcomes of the FOCUS study). Results A total of 303 patients (median age: 63 years, 44.6% women) were included. In >95% of the patients, the expert radiologists could confirm signs of acute PE at baseline CTPA. Radiological signs of chronic thrombi or pulmonary hypertension at baseline were detected in 46 (15.2%) patients. In 8 patients, the expert radiologists agreed on the presence of pre-existing CTEPH based on their interpretation of the overall radiological pattern. During follow-up, five (1.7%; 95% CI 0.7–3.8%) of 303 patients were diagnosed with CTEPH, over a median time of 95 days after baseline. Four of them were among the 8 patients in whom the radiological experts suspected pre-existing CTEPH at baseline, and among the 46 patients in whom CTPA findings suggesting chronic thrombi or chronic pulmonary hypertension were present at baseline. The use of the predefined individual parameters of chronicity from the literature also helped identifying patients with chronic disease, and could be used as a tool for screening acute PE patients for pre-existing CTEPH. Conclusion A substantial proportion of patients who are diagnosed with CTEPH during follow-up after acute PE may already have pre-existing CTEPH at the time of the index event. An intensified follow-up programme and focussed screening for CTEPH should be considered in patients with signs of chronicity at baseline CTPA. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Health Care

Obesity is a growing global concern compounded by limited availability of effective treatment options. The SURMOUNT development program aims to evaluate the efficacy and safety of tirzepatide as an adjunct to lifestyle intervention compared with placebo on chronic weight management in adults with BMI ≥ 27 kg/mThe SURMOUNT program includes four global phase 3 trials NCT04184622 (SURMOUNT-1), NCT04657003 (SURMOUNT-2), NCT04657016 (SURMOUNT-3), and NCT04660643 (SURMOUNT-4). Participants are randomized to once-weekly subcutaneous tirzepatide versus placebo in a double-blind manner. The primary end point in all trials is the percentage change in body weight from randomization to end of treatment. Results for the primary end point for SURMOUNT-1 were published recently and results for the other trials are expected in 2023.Across trials, participants have a mean age of 44.9 to 54.2 years, are mostly female (50.7% to 69.7%), and have a mean BMI of 36.1 to 38.9.The extensive assessment of once-weekly tirzepatide in the global SURMOUNT program will detail the clinical effects of this first-in-class glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist in chronic weight management.

Objective: Obesity and prediabetes are widespread in the U.S., with an estimated 42% of adults living with obesity and 35% living with prediabetes. This research examines the prevalence of comorbidities among people with obesity with or without prediabetes over a 5-year period. Methods: This observational study uses Optum® Market Clarity deidentified data from 2007-2020. For adults with obesity and prediabetes, the index date was defined as the first date where the person was identified with both obesity (BMI ≥ 30 kg/m2) and prediabetes (5.7% ≤ A1c < 6.5%) while for adults with obesity without prediabetes (obesity only) , the index date was defined as the first date with BMI ≥ 30 kg/m2. All patients were required to be continuously insured from 1 year prior through 5 years post index date. For both cohorts, patients were excluded if there was any prior evidence of diabetes and in the obesity only cohort individuals were excluded if identified with prediabetes in the pre-period. Prevalence rates and 95% CIs were calculated for comorbidities for each 365-day period post index date and over the entire 5-year post-period. Results: There were 22,423 individuals with obesity and prediabetes (mean age = 58.5 years; 42.2% male) and 902,975 individuals with obesity only (mean age = 51.7 years; 46.1% male) . The mortality rate after 5 years was 16.7% for adults with obesity and prediabetes and 9.9% for adults with obesity only (p Conclusion: Findings indicate that the presence of prediabetes contributes to the development of additional morbidity and mortality in adults with obesity over time. Disclosure J.Ford: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M.J.Lage: Consultant; Eli Lilly and Company. K.Boye: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.P.Bae: None. K.A.Terrell: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M.C.Bunck: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Purpose: The purpose of the study was to evaluate the midterm and long-term outcomes of patients who underwent thoracic endovascular aortic repair (TEVAR) procedure to treat an uncomplicated acute and subacute type B aortic dissection (uATBAD) with high risk for subsequent aortic complications compared with the group of patients who received a conservative treatment protocol during the same period. Materials and Methods: Between 2008 and 2019, 35 patients who had TEVAR due to uATBAD and those with conservative procedure (n=18) were included in a retrospective analysis and follow-up study. The primary endpoints were false lumen thrombosis/perfusion, true lumen diameter, and aortic dilatation. The aortic-related mortality, reintervention, and long-term survival were the secondary endpoints. Results: In the study period, 53 patients (22 females) with a mean age of 61.1±13 years were included. No 30-day and in-hospital mortality was recorded. Permanent neurological deficits occurred in 2 patients (5.7%). In the TEVAR group (n=35) and in a median follow-up period of 34 months, a significant reduction of maximum aortic and false lumen diameter as well as a significant increase of true lumen diameter were detected (pConclusions: Thoracic endovascular aortic repair in patients at high risk of subsequent aortic complications in uncomplicated acute and subacute type B aortic dissection is safe and is associated with favorable midterm outcomes regarding aortic remodeling. Clinical Impact In a retrospective, single center analysis of prospectively collected data with follow-up, we compared 35 patients with high-risk features who recieved TEVAR in acute and sub-acute uncomplicated type B aortic dissection to a control-group (n=18). The TEVAR group showed a significant positive remoduling (reduction of max. aortic and false lumen diameter and increase of true lumen diameter (p