Pulmonary Disease Research Articles

A new computational framework for simulating airway resistance, fraction of exhaled nitric oxide, and diffusing capacity for nitric oxide.

In this paper, we present a new computational framework for the simulation of airway resistance, the fraction of exhaled nitric oxide, and the diffusion capacity for nitric oxide in healthy and unhealthy lungs. Our approach is firstly based on a realistic representation of the geometry of healthy lungs as a function of body mass, which compares well with data from the literature, particularly in terms of lung volume and alveolar surface area. The original way in which this geometry is created, including an individual definition of the airways in the first seven generations of the lungs, makes it possible to consider the heterogeneous nature of the lungs in terms of perfusion and ventilation. In addition, a geometry can be easily modified to simulate various abnormalities, local or global (constriction, inflammation, perfusion defect). The natural variability of the lungs at constant body mass is also considered. The computational framework includes the possibility to simulate, on a given (possibly modified) geometry, a test to measure the flow resistance of the lungs (including its component due to the not fully developed flow in the first generations of lungs), a test to measure the concentration of nitric oxide in the exhaled air, and a test to measure the diffusion capacity for nitric oxide. This is implemented in the framework by solving different transport equations (momentum and convection/diffusion) describing these tests. Through numerous simulations, we demonstrate the ability of our model to reproduce results from the literature, both for healthy lungs and lungs of patients with asthma or chronic obstructive pulmonary disease. Such a computational framework, through the possibilities of numerous and rapid tests that it allows, sheds new light on experimental data by providing information on the phenomena that take place in the distal generations of the lungs, which are difficult to access with imaging.

Diagnosis: Pulmonary Hypertension. Next Steps.

Pulmonary hypertension (PH) is a disease that is generally first encountered by primary care physicians. Usually, patients present with dyspnea on exertion and a loss of exercise tolerance, although they can have symptoms of chest discomfort, syncope, or edema. Most patients are diagnosed with 2 dimensional doppler echocardiography although echo is not 100% sensitive nor specific in making this diagnosis. Note that the diagnostic criteria for this disease have changed recently. Most patients develop pulmonary hypertension secondary to left heart failure, or to pulmonary disease with or without hypoxemia. Ultimately, many patients require right heart catheterization for diagnosis and for proper treatment. This is best performed by those that specialize in management of this disease. It is important to diagnose patients who have pulmonary hypertension due to pulmonary artery hypertension and patients with chronic thromboembolic pulmonary hypertension as these patients require specialized treatment that is most effective if started early in the disease course. This review discusses issues related to diagnosis and appropriate referral of patients with pulmonary hypertension.

Coping With Chronic Obstructive Pulmonary Disease Together: A Dyadic Study of Self-Care and Quality of Life in Patients and Their Caregivers.

To investigate the relationship between self-care and quality of life (QOL) in patients with chronic obstructive pulmonary disease (COPD) and their caregivers. A multicentre, cross-sectional study. COPD patients and their caregivers were recruited from four tertiary hospitals in Jinan, Shandong Province, China from March to November 2022. Data collection included demographic and clinical characteristics, patients' self-care, caregivers' contribution to patient self-care, and QOL. Statistical analysis included descriptive statistics, paired t-tests, Pearson correlations and Actor-Partner Interdependence Model (APIM) analyses. A total of 275 valid questionnaires were collected (patients: 67.6% male, mean age 70.5; caregivers: 58.5% female, mean age 54.2). APIM analyses revealed actor effects of self-care on QOL for both patients and caregivers, as well as partner effects indicating the influence of one's self-care on the partner's QOL. This study elucidates the dyadic relationship between self-care and QOL in COPD patients and caregivers. Higher levels of self-care maintenance by both patients and caregivers were associated with improved physical and mental QOL. Conversely, increased self-care monitoring was correlated with reduced QOL for both patients and caregivers. No significant relationship was found between self-care management and QOL. For healthcare professionals specialising in geriatric care, our research provides more valuable guidance for the nursing of COPD patients. While maintaining vigilance is essential for both COPD patients and caregivers, our study suggests that excessive monitoring may have adverse effects on QOL, though this impact may vary depending on the underlying need for monitoring. This underscores the importance of tailored interventions that balance necessary vigilance with the potential risks of over-monitoring. By carefully considering the motivations behind monitoring, professionals can better support both patients and caregivers, ultimately enhancing self-care, improving QOL and contributing to healthy ageing. The STROBE checklist was used to report the present study. During the research design phase, we conducted interviews with patients and caregivers to capture pertinent issues related to their daily self-care routines. This initial step allowed us to gain an understanding of the potential differences between patients' self-care levels and caregivers' contributions to patients' self-care, while also exploring the potential impact on their health. Prior to data collection, we conducted a pilot study to identify any shortcomings in the research design and made corresponding adjustments. The phrasing of questions in the questionnaire was refined based on the feedback from patients and caregivers. During the interpretation phase, we solicited feedback from a subset of patients and caregivers to further validate our findings, thereby enhancing the clarity and relevance of our results for the target audience.

Speckle tracking echocardiography has an additive value to differentiate pulmonary hypertension associated with left heart or lung diseases in patients presenting with dyspnoea

Abstract Background The diagnostic pathway of pulmonary hypertension (PH) is complex and requires several parameters. Differential diagnosis between left heart disease (group 2) and pulmonary disease (group 3) as PH etiology is also challenging. The latest European guidelines recommend a comprehensive echocardiographic evaluation for suspected PH, and the use of several basic echocardiographic indices to assess cardiac etiology of PH. Speckle tracking echocardiography (STE) has emerged as a more sensitive technique to evaluate myocardial performance in different clinical settings and is recommended for the diagnosis of HFpEF. Purpose Our ai was to assess the potential value of STE to predict left heart disease in patients presenting with dyspnoea and PH. Methods Consecutive outpatients with dyspnoea with efforts and subsequent diagnosis of PH were retrospectively enrolled. Inclusion criteria were New York heart association (NYHA) class≥II, LV ejection fraction≥50%, echocardiographic evidence of systolic pulmonary artery pressure≥35 mmHg and tricuspid regurgitant velocity≥2.8 ms, known diagnosis of PH with relative etiology (heart failure with preserved ejection fraction, HFpEF or lung diseases i.e. sarcoidosis, idiopathic pulmonary fibrosis, chronic obstructive lung disease). Patients underwent clinical, biohumoral and echocardiographic evaluation, STE was performed offline. Primary endpoint was the prediction of HFpEF. Results Overall, 145 patients were enrolled (80 with HFpEF, 65 with lung disease). Mean age was 75±12 years, 53% were female. Patients with HFpEF were older (77±10 vs. 68±14 years, p<0.0001) and had higher LA volume (93±37 vs. 64±31 ml, p<0.0001), E/E’ by tissue Doppler imaging (TDI) (15±5 vs. 9±3, p<0.0001), mitral regurgitation (MR) grading (p=0.002), lower tricuspid regurgitation (TR) grading (p=0.004). Regarding STE, patients with HFpEF had lower peak atrial longitudinal strain (PALS) (15 ± 8 vs. 24 ± 11%, p<0.0001) and LV global longitudinal strain (-13 ± 9 vs. -17 ± 6%, p=0.009). LA stiffness, calculated as the ratio between E/E’ and PALS, an index of LA dysfunction and fibrosis, was higher in patients with HFpEF (median LA stiffness = 1.09 [CI = 0.64-1.73] 0. Vs.0.35 [CI = 0.20-0.59], p<0.0001). With ROC curves, both E/E’ and global PALS provided a good prediction for HFpEF (AUC 0.73 and 0.79 respectively), but LA stiffness significantly enhanced the predictive power (AUC = 0.83) with an optimal cutoff value ≥0.53. With multivariate analysis including age, LA volume, LV GLS, LA stiffness, mitral and tricuspid regurgitation grade, LA stiffness≥0.53 (RR = 19.14, CI 5.86-62.55) was the only independent predictor of HFpEF in our cohort of patients with PH (Fig.1). Conclusions STE may aid differential diagnosis of etiology between left heart disease and pulmonary disease in patients with PH. The combination of TDI E/E’ and PALS to calculate LA stiffness offers the most accurate prediction of PH with cardiac etiology.

Dyspnoea and atypical angina: two sides of the same coin?

Abstract Introduction the latest guidelines from the European Society of Cardiology introduce dyspnoea into the risk stratification for patients with suspected coronary artery disease, equating it with atypical angina in terms of pre-test probability. Traditionally, dyspnoea has been considered an angina equivalent in certain patients, although its origin is often due to non-cardiological pathologies. Furthermore, the percentage of patients presenting with dyspnoea without chest pain and with ischaemia on stress tests varies widely across studies. Objectives the aims of our study were to determine the profile of patients referred to our Cardiac Imaging Unit for coronary artery disease screening whose symptom were dyspnoea or atypical angina, to assess the percentage of studies with induced ischaemia in this population, and to compare this percentage between the two groups of patients. Methods retrospective analysis including 626 consecutive patients who presented to our centre for stress echocardiography to screen for unknown coronary artery disease and whose referral symptons were atypical angina or dyspnoea without chest pain. To compare the probability of presenting ischaemia between the two groups, a 1:1 propensity score matching analysis was performed, incorporating traditional risk factors, as well as age, sex, body mass index (BMI), peripheral arterial vascular disease, pulmonary disease, obstructive sleep apnoea, anxiety-depressive syndrome, beta-blocker or contrast agents use, and baseline wall motion or electrocardiogram abnormalities. Results of the 626 patients, 149 (24%) were referred for dyspnoea without chest pain. Compared to patients presenting with atypical angina, those with dyspnoea were older (69.9 years vs 64.8 years, p<0.01), had a higher BMI (29.7kg/m² vs 28.8kg/m², p=0.05), and a higher prevalence of hypertension (71% vs 58%, p=0.006), diabetes mellitus (40% vs 28%, p=0.006), dyslipidaemia (68% vs 56%, p=0.009), and pulmonary disease (24% vs 12%, p<0.001). Patients referred for dyspnoea underwent pharmacological stress echocardiography more frequently (35% vs 20%, p<0.001) and contrast agents were used more often (30% vs 21%, p=0.020), with basal wall motion abnormalities observed more frequently (14% vs 5%, p<0.001). The percentage of studies with induced ischaemia in the dyspnoea group was slightly higher (6% vs 4%), but this difference was not statistically significant (p=0.349). Propensity matching score analysis did not reveal a higher odds of ischaemia in the dyspnoea group (OR 1.00, p=0.921, 95% CI 0.94-1.06). Conclusions the percentage of positive studies in patients referred for dyspnoea or atypical angina was low in both groups. Despite the higher prevalence of risk factors in the dyspnoea referral group, the likelihood of ischaemia on stress echocardiography is very similar between the two groups. Clinical and stress characteristics Balance plot between groups

P-1812. Artificial Intelligence Modeling and Implementation in Antimicrobial Stewardship Program at a Tertiary Medical Center in Taiwan

Abstract Background Antimicrobial stewardship program (ASP) aim to promote appropriate antibiotic use and preventing antimicrobial resistance. Personalized tools using artificial intelligence (AI) to provide tailored antibiotic recommendations to healthcare providers may transform the way we approach antibiotic stewardship.Figure 1Rate of Multidrug-Resistant Organisms by Department Methods The study included all patients (age > 12) admitted to Chang Gung Memorial Hospital from January 1, 2005, through January 31, 2022, who had been prescribed antibiotics after admission and had microbiological evidence within the hospitalization. We conducted a linear regression equation to explore the relationship between antibiotic heterogeneity index (AHI) and multidrug-resistant organisms (MDROs) ratio in different units of hospital. We used a variety of machine learning algorithms to evaluate the incremental value of various variable groups of patients, and developed an AI model for predicting MDRO infections and antimicrobial de-escalation during hospitalization.Figure 2Value of Antibiotic Heterogeneity Index by DepartmentAHI: antimicrobial heterogenecity index Results There were 789,259 individuals fulfilled the including criteria. Figure 1 shows the incidence rates of MDROs across 19 departments, ranging from 3.2% in oncology to 10.7% in thoracic medicine. AHI for each department was ranging from 0.42 in neurosurgery to 0.74 in thoracic medicine (figure 2). Linear regression for the relationship between AHIs and MDRO incidence rates, represented a regression coefficient β of 0.179 (p-value: 0.02), indicating a statistically significant difference, with an R-squared of 0.47. Variables considered in modeling analysis of MDRO infection and antimicrobial de-escalation were shown in table 3. Random Forests with model 3 variables had the best (97%) positive predictive value (PPV) among five machine learning model in predicting MDRO infection, and the performance is much better than traditional linear regression (Figure 4). However, the best predicting model for antimicrobial de-escalation had only 43% PPV in Random Forests with model 5 variables.Table 3Variables Considered in Modeling Analyses of Multidrug-Resistant Organisms and Antibiotic De-escalation Tiered on Feasibility of Measurement Conclusion High AHI had positive correlation with high MDRO incidence. AI modeling had a great performance in predicting MDRO infection. Early predicted high risk group can be an important special population for ASP implementation.Figure 4Model Performance of Classification for Multidrug-Resistant Organisms by Input Variable Feasibility Tier Model 1 included tier 1 factors as predictor variables to predict interested outcome; model 2 included both tier1 and tier2 as predictor variables; model 3 use tier1 to tier3 as predictor variables; model 4 included tier1 to tier3 variables and plus tier 4 factors which contains continuous laboratory variables as predictor variables and model 5 included tier1 to tier3 variables and plus tier 5 factors which contains categorical laboratory variables as predictor variables. Disclosures All Authors: No reported disclosures

P-1920. The influence of comorbidity, age, sex, and immunosuppression on COVID-19 mortality throughout the course of the SARS-CoV-2 pandemic in Europe: Data from the LEOSS study

Abstract Background Population immunity against SARS-CoV-2 has increased, resulting in a decline of COVID-19 mortality. The aim of the study was to analyse the COVID-19-related mortality over the pandemic, stratified by a model of groups at risk of severe COVID-19. Predicted probability of COVID-19-related death in dependence of age and SARS-CoV-2 variant. Methods COVID-19-related patients were included from January 2020 to November 2022 using the international multicentric cohort study Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS). Predicted probability of COVID-19-related death was calculated using a multivariate logistic regression model adjusted to age, gender and vaccination status.Figure 2:Predicted probability of COVID-19-related death in dependence of gender and SARS-CoV-2 variant. Results In total, 12,096 patients were included. The overall mortality was 13% (n=1546), decreasing from 14% during the wildtype (wt) period (01/2020-12/2020), to 13%, 10%, and 6% in the alpha (α) (01/2021-06/2021), delta (δ) (07/2021-12/2021), and omicron (Ω) (01/2022-11/2022) periods, respectively. Patients aged 66-75, 76-85, and >85 years (y) had a 13.3-, 22.5-, and 40.4-fold higher odds of mortality compared to 26-35y old patients (p< 0.001 in all listed comparisons). This increase in mortality between younger (age: 26-35y, mortality: wt 2%, Ω 1%) and older patients (age: >85y, mortality: wt 41%, Ω 23%) decreased with the shift from wt (increase of 39 percentage points) to Ω (increase of 22 percentage points) (Fig. 1). The overall mortality in males (m) (15%) was higher than in females (f) (10%), but this gender-specific difference leveled off with the shift from wt (m: 19%, f: 10%) to Ω (m: 9%, f: 9%) (Fig. 2). Referring to the difference in mortality between patients with zero and four comorbidities, the predicted increase in mortality during the periods wt, α, δ, and Ω was 14, 14, 1, and 0 percentage points, respectively (Fig. 3). Concerning severely immunosuppressed patients, mortality significantly decreased throughout the pandemic (wt: 15%, Ω: 4%, p=0.031) (Fig. 4).Figure 3:Predicted probability of COVID-19-related death in dependence of number of comorbidities and SARS-CoV-2 variant.Comorbidities include cardiovascular diseases, renal diseases, diabetes, pulmonary diseases, liver diseases, rheumatic diseases, haemato-oncological diseases, neurological diseases, autoimmune diseases and HIV/AIDS. Conclusion Overall mortality decreased during the pandemic. This change was observed even among severely immunosuppressed patients. Age, gender, and the number of comorbidities were identified as relevant mortality risk factors, with decreasing importance as the pandemic progressed.Figure 4:Subgroup analysis for severely immunosuppressed patients.Severely immunosuppressed group, including: stem cell transplant, organ transplant, b-cell depletion, autoimmune disease, immunosuppressive therapy (corticosteroids, methotrexate, azathioprine, ciclosporin, calcineurin-inhibitors, mTOR-inhibitors). Disclosures Jochen Schneider, n/a, AbbVie: Grant/Research Support|AbbVie: Honoraria|AbbVie: non-financial support|Central Innovation Program for small and medium-sized enterprises: Grant/Research Support|Central Innovation Program for small and medium-sized enterprises: Honoraria|Central Innovation Program for small and medium-sized enterprises: Central Innovation Program for small and medium-sized enterprises|Deutsche Forschungsgemeinschaft: Grant/Research Support|Deutsche Forschungsgemeinschaft: Honoraria|Deutsche Forschungsgemeinschaft: non-financial support|Diasorin: Grant/Research Support|Diasorin: Honoraria|Diasorin: non-financial support|Dr. Falk Pharma GmbH: Grant/Research Support|Dr. Falk Pharma GmbH: Honoraria|Dr. Falk Pharma GmbH: non-financial support|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Gilead Sciences: non-financial support|GSK/ViiV Healthcare: Grant/Research Support|GSK/ViiV Healthcare: Honoraria|GSK/ViiV Healthcare: non-financial support|Janssen-Cilag: Grant/Research Support|Janssen-Cilag: Honoraria|Janssen-Cilag: non-financial support|MSD: Grant/Research Support|MSD: Honoraria|MSD: non-financial support|Takeda Pharmaceutical: Grant/Research Support|Takeda Pharmaceutical: Honoraria|Takeda Pharmaceutical: non-financial support Christoph Spinner, MD, AbbVie: Honoraria|Apeiron: Honoraria|AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|BBraun Melsungen: Honoraria|BBraun Melsungen: non-financial support|BioNTech: Honoraria|Cepheid: Grant/Research Support|Eli Lilly: Honoraria|Formycon: Honoraria|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Gilead Sciences: non-financial support|GSK: Honoraria|Janssen-Cilag: Grant/Research Support|Janssen-Cilag: Honoraria|Molecular partners: Honoraria|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Honoraria|Roche: Honoraria|Shionogi: Honoraria|SOBI: Honoraria|Synairgen: Honoraria|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Maria JGT Vehreschild, Prof. Dr. med., 3M: Honoraria|Ärztekammer Niedersachsen: Honoraria|ADKA: Honoraria|Akademie für Infektionsmedizin: Honoraria|Astellas: Honoraria|Berliner Dialy Seminar: Honoraria|Biontech: Grant/Research Support|CED Service: Honoraria|DiaLog Service: Honoraria|EUMEDICA: Advisor/Consultant|EUMEDICA: Honoraria|Falk Foundation: Honoraria|Ferring: Honoraria|Forum für medizinische Fortbildung Gmbh: Honoraria|GILEAD: Honoraria|Heel: Grant/Research Support|Helios Kliniken: Honoraria|Institute Merieux: Honoraria|Janssen: Honoraria|Kit Kongress: Honoraria|Klinikum Essen: Honoraria|Klinikum Leverkusen: Honoraria|Lahn-Dill-Kliniken: Honoraria|Landesärztekammer Hessen: Honoraria|Limbach Gruppe SE: Honoraria|MaaT: Advisor/Consultant|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Honoraria|Roche: Advisor/Consultant|Roche: Grant/Research Support|SD Biosensor: Grant/Research Support|St. Johannes Hospital: Honoraria|St. Josef Hospital: Honoraria|SUMIT OXFORD Ltd.: Honoraria|Tillotts: Advisor/Consultant|Tillotts: Honoraria|Uniklinik Frankfurt: Honoraria|Uniklinik Köln: Honoraria|Uniklinik Karlsruhe: Honoraria|Universitätsklinikum Freiburg: Honoraria|Universitätsklinikum Heidelberg: Honoraria Floran Voit, MD, Gilead Sciences: Honoraria|Gilead Sciences: non-financial support|MSD: Grant/Research Support|Pfizer: non-financial support|ViiV Healthcare: non-financial support Johanna Erber, Dr. med., Gilead Sciences: non-financial support|Pfizer: non-financial support|Tillotts Pharma AG: non-financial support|ViiV Healthcare: non-financial support

Natural Compounds Regulate Macrophage Polarization and Alleviate Inflammation Against ALI/ARDS

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a pulmonary disease with high mortality associated with inflammation. During the development of ALI/ARDS, macrophages usually polarize toward M1 pro-inflammatory macrophages, promoting the inflammatory response in ALI/ARDS and aggravating lung tissue damage. Natural compounds with anti-inflammatory activity have achieved excellent results in the treatment of ALI/ARDS through different regulatory modes, including macrophage polarization. Of note, flavonoid, brevilin A, and tetrahydropalmatine play an important role in the treatment of ALI/ARDS by modulating the phenotypic polarization of macrophages and their pro-inflammatory cytokine expression in innate immune cells of the lung. Flavonoids are a kind of naturally occurring polyphenol compound, which has antioxidant and anti-inflammatory activities. Studies have found that some flavonoids can alleviate ALI/ARDS through inhibiting the expression of inflammatory cytokines in macrophages. Among them, 5-methoxyflavone, acacetin, grape seed proanthocyanidins, and luteolin can also regulate macrophage polarization. Therefore, the in-depth exploration of the regulatory mechanism of macrophages can lay the foundation for the application of flavonoids in alleviating inflammation-related lung injury. This review focuses on the macrophage polarization effects of different natural compounds and their potential anti-inflammatory mechanisms in the treatment of ALI/ARDS.

Risk Factors for Clostridium difficile Infection in Inpatients: A Four-Year (2017–2020) Retrospective Study

Background: Clostridium difficile infection (CDI) impact on healthcare systems is concerning due to high treatment cost and increased hospitalization time. We found that the incidence rate of CDI increased annually at Taipei Medical University Hospital (TMUH). The study aimed to establish monitoring indicators for hospitalized patients receiving antibiotics to prevent CDI occurrences. Methods: A case–control study was conducted to identify the risk factors of CDI among patients who were admitted to TMUH and tested for C. difficile. Patient demographics, patient history, and laboratory data were collected and analyzed. Results: Nutrition Risk Screening 2002 score (NRS 2002) in CDI patients was significantly lower than in non-CDI patients (3.1 ± 1.7 vs. 3.5 ± 1.6). The percentage of tube feeding in CDI patients was significantly lower than in non-CDI patients (23.0% vs. 36.7%), whereas parenteral nutrition was higher (8.8% vs. 3.8%). Age (OR = 1.03, p = 0.00), NRS 2002 score (OR =0.86, p = 0.05), comorbidity with cardiovascular disease (OR = 1.73, p = 0.03) or pulmonary disease (OR = 3.72, p = 0.00), patients with tube feeding (OR = 2.02, p = 0.01), and the number of medications (OR = 1.15, p < 0.01) were significant predictors of CDI. Conclusion: This study revealed that nutritional factors, including NRS 2002 scores and feeding routes, were associated with CDI, emphasizing the importance of nutritional factors as key predictors in managing and preventing CDI.

NHERF2 as a Novel Biomarker for Distinguishing MAC Pulmonary Disease from Tuberculosis Based on Proteome Analysis of Serum Extracellular Vesicles

Nontuberculous mycobacterial pulmonary disease (NTM-PD), mainly caused by Mycobacterium avium complex (MAC), and pulmonary tuberculosis (TB) are emerging health problems worldwide. However, because their clinical features are often similar, it remains difficult to differentiate NTM-PD from TB when the diagnosis cannot be made by sputum culture. To investigate potential serum biomarkers, we conducted non-targeted proteome analysis on serum extracellular vesicles (EVs) collected from 10 patients with MAC pulmonary disease (MAC-PD), 7 patients with TB, and 10 healthy controls. A total of 2614 proteins were identified in the discovery cohort. The EV protein signature from patients with NTM-PD and TB reflected infectious diseases and inflammatory response pathways. Among the identified proteins, the expression of Na+/H+ exchanger regulatory factor 2 (NHERF2) was significantly elevated in patients with MAC-PD compared with healthy controls and patients with TB. Moreover, upregulation of NHERF2 was confirmed by immunoblotting of serum EVs and immunohistochemistry of lungs with mycobacterial infection. Our findings highlight that NHERF2 in serum EVs might be a potential biomarker for distinguishing MAC-PD from TB, possibly reflecting the pathogenesis of MAC-PD.

P-793. Long-term Outcomes of Mycobacterium avim complex Pulmonary Disease in Kyushu, Japan: A Retrospective Multicenter Study

Abstract Background Recently, the number of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has increased worldwide. The most common causative organism in Japan is the Mycobacterium avium complex (MAC). The incidence of MAC pulmonary disease (MAC-PD) is higher than that in other countries, and deaths from MAC-PD are increasing. Complex cases involving radiological fibrocavitary patterns and pulmonary aspergillosis have been reported as poor prognostic factors; however, available evidence is limited. To address this gap, we initiated a retrospective, multicenter study in Kyushu, Japan, focusing on the long-term prognosis of patients five years after the diagnosis of MAC-PD. The primary objective of this study was to investigate the factors that influence the outcomes of these patients by employing data accessible at the time of their initial diagnosis. Methods This was a retrospective cohort study of patients aged ≥ 18 years with newly diagnosed NTM-PD who visited 18 medical centers in Kyushu, Japan, between 2010 and 2017. Patient data were collected from medical records by respiratory experts and recorded using the EDC. Results The study enrolled 1317 patients with NTM-PD, of whom 1214 had MAC-PD. Patients with insufficient information were excluded, and 856 patients were analyzed: 546 (63.8%) with a non-cavitary nodular bronchiectatic (NB) pattern and 194 (22.7%) with a cavitary NB or fibrocavitary pattern. 107 (12.5%) died from all-cause by 5 years after diagnosis and 137 (16.0%) by 10 years; in the group that died after 5 years, the following were detected as risk factors in multivariate analysis: male sex (OR = 2.90, 95% confidential interval 1.84-4.56), age ≥ 70 (OR = 2.20, 95%CI 1.33-3.63), lobes with cavities ≥ 2 lobes (OR = 2.16, 95%CI 1.07-4.36), albumin < 3.5 g/dL (OR = 3.68, 95%CI 2.29-5.91), and oral corticosteroids (OR 1.97, 95%CI 1.04-3.73). Conclusion Male sex and fibrocavitary patterns have been reported to be poor prognostic factors for MAC-PD. In our study, we found that cavitary formation in more than two lobes, lower albumin levels, and oral corticosteroids were newly considered poor prognostic factors. We believe that our findings may help determine treatment induction and predict the prognosis of MAC-PD. Disclosures Hiroshi Mukae, M.D., Ph.D., AstraZeneca: Lecture fees|Gilead Sciences: Lecture fees|GSK: Lecture fees|MSD: Advisor/Consultant|MSD: Lecture fees|Pfizer: Lecture fees|Shionogi & Co., Ltd.: Advisor/Consultant|Shionogi & Co., Ltd.: Grant/Research Support|Shionogi & Co., Ltd.: Lecture fees

Is dyspnea the new angina?

Abstract Introduction The exercise stress echocardiogram is a highly valuable tool for evaluating patients with dyspnea as the main symptom (without angina) and suspected coronary artery disease (CAD). This involves a large volume of patients in daily practice, and etiological orientation is often difficult, especially in patients with high cardiovascular risk. Objective This study aims to define the likelihood of inducible ischemia in this population concerning their pretest probability described in the literature, as well as to compare the exercise workload achieved during the test with the predicted workload. Methods We performed a retrospective analysis of 116 consecutive diagnostic exercise stress echocardiograms (2021-2023) conducted on patients with dyspnea as the main symptom (14.55% of the total exercise stress echocardiograms). Results The average age was 67.93 years (standard deviation [SD] 9.99), and the average body mass index (BMI) was 28.87 (SD 4.37). Baseline characteristics included hypertension (79 patients, 68.1%), diabetes (39 patients, 33.6%), dyslipidemia (76 patients, 65.5%), smoking (46 patients, 39.7%), and known pulmonary disease (21 patients, 18.1%). Among the patients, 104 (89.7%) had an intermediate pretest probability of CAD. The main reason for test termination was dyspnea in 78 patients (67.2%). The average maximum workload achieved was 7.28 METs (SD 2.34), compared to a predicted maximum workload of 6.58 METs (SD 1.78), resulting in an actual/predicted METs ratio of 1.14. The stress echocardiogram was positive for inducible ischemia in 8 cases (6.9%), with no significant differences between diabetic and non-diabetic patients (6.49% positive in non-diabetics, 7.89% positive in diabetics, p = 0.781). Conclusions Patients referred for dyspnea as the main symptom demonstrated greater functional capacity than predicted, suggesting both a challenging assessment of functional class in clinical consultations and a possible underestimation of age-predicted functional capacity formulas in the current population. Additionally, the positivity rate for ischemia was lower than described in the literature for a population with predominantly intermediate pretest probability of CAD. Salgo le characteristics

P-782. Nontuberculous Mycobacterial Infections among Lung Transplant Recipients: A Nine-Year Cohort Study

Abstract Background The epidemiology, microbiology, and clinical course of nontuberculous mycobacterial (NTM) infection among lung transplant recipients vary considerably by geographic location. Their data is still scarce. Methods This single-center retrospective study was conducted at one of the major transplant centers in Japan. Medical records and microbiological test results of all the lung transplant recipients who underwent lung transplants between 2015 to 2023 were reviewed through December 31, 2023. Per institutional protocol, tracheal aspirates or sputum have been sent for mycobacterial cultures at the time of transplant and when clinically indicated thereafter. The definition of pulmonary NTM disease was based on the ATS/ERS/ESCMID/IDSA guidelines. Results In total, 175 lung transplants were performed during the study period (Table 1). Before transplant, 7 recipients had NTM isolation from the sputum and 5 of these 7 recipients had received bilateral lung transplants. While only 2 of these 7 recipients met the diagnosis of NTM pulmonary disease, 6 recipients received antimycobacterial treatment for a median duration of 25 months before transplant and only one case had NTM isolation after transplant (Figure 1). At the time of lung transplant, 169/175 (97%) recipient’s sputum were collected. Six species of NTM were isolated in 18 patients (10%, 18/175) at various times; at the time of transplant, between 0-1 month, 1-6 months, 6-12 months, and after 12 months in 2, 7, 3, 2, and 5 recipients, respectively (Figure 1, 2). Twenty-two isolates were recovered at the time of and after transplant, slowly growing mycobacteria accounted for 86% (19/22), including M. avium complex (N = 12) and M. gordonae (N = 4), whereas rapidly growing mycobacteria, M. fortuitum (N = 2) and M. chelonae (N = 1), accounted for the rest. Although 2 of 18 recipients with NTM isolation died, one recipient died directly from NTM infection complicated by Aspergillus coinfection. Conclusion NTM were isolated in 10% of recipients at the time of and after lung transplant. NTM, isolated before and at the time of transplant, rarely required treatment after transplant. Disclosures All Authors: No reported disclosures

P-342. Outcomes of Human Metapneumovirus in Nursing Home Residents: A Matched Analysis

Abstract Background Identified in 2001, human Metapneumovirus (hMPV) is a Paramyxoviridae with bimodal age distribution - affecting children and older people. In older people, clinically severe hMPV may be associated with respiratory symptoms resulting in hospitalization and/or death. The purpose of this study was to compare hospitalization and death in older nursing home residents with hMPV or influenza. Methods Using the electronic medical records of VA Community Living Centers (CLC) during the epidemiology years of Sept 1, 2017 to August 31, 2023, we identified CLC residents who tested positive for hMPV or influenza. We collected information on demographics and comorbidities, as well as clinical testing. We developed a propensity matched cohort of hMPV and influenza positive CLC residents and used proportional hazards models to determine the hazard ratio (HR) for hospitalization, death or either during the 90 days after positive test among hMPV- and influenza-positive residents. Results During the study period, we identified 135 hMPV infections and 1170 influenza. Most hMPV included influenza testing and there were no co-infections. Both populations were older (hMPV 76.1 (10.6) vs. influenza 74.2 (10.9) years, SMD=0.18) and predominantly male (hMPV 96.7% vs. influenza 96.3%, SMD=0.02). The hMPV cohort had more pulmonary disease (42.2% vs 30.9%, SMD=0.25) and dementia (55.6% vs. 42.3%, SMD=0.26) compared to influenza cohort. The propensity matching identified 130 hMPV and 601 influenza residents that were well matched. proportional hazard model on the propensity matched cohort found equivocal hazard for hospitalization (adjusted HR 0.91 (0.55, 1.50)), death (adjusted HR 1.03 (0.61, 1.75)), and the combined outcome (adjusted HR 0.92 (0.61, 1.33)). Conclusion When hMPV develops in nursing home residents, the outcomes of hospitalization and death are comparable to influenza. Increased awareness of hMPV and appropriate point of care testing are needed to accurately detect hMPV and implement infection control measures. Additional studies are needed to better understand epidemiology, prevention, and treatment of hMPV in especially high-risk nursing home residents. Funded by Icosavax, a member of the AstraZeneca Group Disclosures Yasin Abul, MD, Moderna: Grant/Research Support|Moderna, Abt, CDC: Grant/Research Support Kevin McConeghy, Pharm.D., Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Stefan Gravenstein, MD, MPH, CDC: Advisor/Consultant|CDC: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|Genentech: Honoraria|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Honoraria|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Advisor/Consultant James L. Rudolph, MD, Icosavax / AstraZeneca: Grant/Research Support

P-1815. Estimation of the cases with suspected community-acquired pneumonia where antibiotic intervention could occur after 48 hours: Application of an electronic algorithm for real-time screening

Abstract Background Timely identification of unnecessary antibiotics (abx) started for suspected community-acquired pneumonia (CAP) is vital for antibiotic stewardship programs (ASPs). We estimated potential opportunities for ASP intervention among patients flagged as potentially having CAP by an electronic algorithm using electronic health record data that allows for real-time case detection. Methods We screened all adult patients admitted to Johns Hopkins Hospital (1,150 beds) between 12/2023-2/2024 using the algorithm which is based on the following variables: i) abx targeting CAP ≥48h, ii) respiration rate ≥24/min, iii) white blood cell (WBC) >12,000/mm3, and iv) natural language processing (NLP)-derived radiology results compatible with pneumonia. Patients admitted to oncology or with sickle cell disease were excluded. Manual chart review was performed to adjudicate true CAP, defined as the presence of signs/symptoms of pneumonia with corresponding radiographic findings, while excluding alternative diagnoses, based on the clinical course observed within 48 h. We characterized factors associated with patients without CAP, particularly radiological interpretation, and the proportion eligible for ASP intervention at 48 h of admission. Results 122 of the 152 cases (80.3%) identified by the electronic algorithm were adjudicated as non-CAP based on clinical criteria. Compared to CAP cases, non-CAP cases were less likely to have fever (40.0% vs. 9.8%, P < 0.001) and cough/sputum (76.7% vs. 42.6%, P = 0.001). Common diagnoses for non-CAP cases were volume overload (19.7%), other pulmonary disorders (18.9%), chronic lung disease exacerbation (14.8%), and viral pneumonia (12.3%). Most unnecessary abx were initiated in the emergency room (85.2%, 104/122); 60.6% (63/104) were continued for >24 hours after admission, and 48.4% (59/122) could have been intervened upon at 48 hours of admission. 63.1% of non-CAP cases had radiographic interpretations suggesting CAP, with poor correlation between radiological interpretation and clinical diagnosis of true CAP (kappa 0.221). Conclusion ASP interventions to stop abx within 48 h of admission were indicated in ∼50% of non-CAP cases identified by the electronic algorithm. Disclosures All Authors: No reported disclosures

Branch pulmonary artery flows calculated using velocity time integral correlate with MRI in pediatric pulmonary vein stenosis

Abstract Background/Introduction In pulmonary vein stenosis (PVS), serial echocardiograms are the mainstay in assessment of pulmonary vein disease. Development of gradients in stenotic pulmonary veins indicate progression of disease and influences timing of intervention. However, pulmonary vein gradients should be interpreted in the context of relative branch pulmonary artery (PA) flows to avoid misinterpretation of worsening PVS. To date, the comparison of branch PA flows derived from echocardiography compared to gold-standard from MRI has not been described. Purpose To determine if branch PA flows calculated using velocity time integral (VTI) correlate with MRI. Methods Single-center retrospective assessment of cardiac MRIs and echocardiograms in pediatric patients with pulmonary vein stenosis between February 2019 to May 2022. Cardiac MRIs and echocardiograms obtained within a 6-month period were compared. All causes and severity of PVS were included. Patients were excluded if echocardiographic assessment did not adequately visualize either branch PA or pulse wave Dopplers in the PAs were not performed. 20 patients with a mean age of 7.72 ± 5.93 years were included. Branch PA flows were derived using PA diameter in systole from the high parasternal view from which cross-sectional area (CSA) was calculated using CSA = pi(radius)^2. Using pulse wave Doppler in the branch PAs, VTI was measured as an averaged area under the curves over 3 beats. Relative branch PA flows were calculated using a product of CSA and VTI. We present branch PA flows indexed to body surface area. Results Mean RPA flows by VTI and MRI were 2.18 ± 1.36L/min/m2 and 2.34 ± 1.29L/min/m2, respectively. Mean LPA flows by VTI and MRI were 1.64±0.77L/min/m2 and 1.94±1.13L/min/m2, respectively. There were statistically significant correlations in branch PA flows comparing VTI to MRI (RPA correlation coefficient 0.549, p=0.02, LPA correlation coefficient 0.621, p=0.01). Conclusion Relative branch PA flows calculated using VTI correlate significantly with gold-standard from MRI. Lower correlation in the RPA may be due to Doppler angle. This is a feasible, complementary tool easily integrated as part of the standard echocardiographic assessment of PVS, that allows early detection of disease progression while decreasing the frequency of general anesthesia required for MRIs in young children. Expansion to a larger cohort is necessary to strengthen demonstrated correlations. Future work includes integration of branch PA flows in addition to pulmonary vein gradients to develop a PVS severity score in pediatrics to guide management.

Right ventricular volumes and function indices by automated 3D speckle tracking echocardiography with artificial intelligence software

Abstract Introduction Normal values of three dimensional right ventricular (RV) volumes, ejection fraction (EF) and systolic function indices by three - dimensional speckle tracking echcardiography (3D - STE) are not well established. All measurements relied on older 3D RV software analysis and most of these are operator - depended with a wide variability in measured values. The gold standard method for evaluation of RV volumes and EF remains the Magnetic Resonance Imaging (MRI)despite the rapid improvement in echocardiography softwares for RV evaluation. Purpose Aim of the study was to assess the feasibility of modern advanced technology echocardiographic software based on 3D imaging powered by Artificial Intelligence (AI) in measurement of RV volumes, RV EF and systolic function indices by 3D - STE in normal subjects. Methods Healthy subjects without any cardiovascular, pulmonary and renal disease, underwent complete echocardiographic evaluation including the 3D datasets from each of the parasternal, apical and subcostal views. 3D RV datasets were obtained and analyzed using RV software powered by AI, to measure Global RV Volumes, End - Diastolic volume (EDV), End - Systolic volume (ESV), RV EF and Tricuspid Annular Plane Systolic Excursion (TAPSE). Additionally 3D Free Wall Longitudinal Strain (FWLS) and 3D Global Strain (3D GS) were obtained. Three or more datasets obtained from the apical view were available for comprehensive analysis in each subject. Results Of the 54 healthy subjects, 40 (50% male and 50% female, mean age 51 +/- 15 years old) had adequate image quality for measurements. Mean indexed 3D EDV, ESV and RV EF were measured at 48.5 +/- 10.3 mL/m2, 16.7 +/- 5.8 mL/m2, 56,1 +/- 5.9 % respectively. in addition 3D FWLS and 3D GS were measured at - 27.9 +/- 4.5 % and - 24.7 +/- 3.6 % respectively. TAPSE was measured at 22.4 +/- 5.1 mm. Conclusions Modern softwares based on AI are a new era in Cardiology and Echocardiography. A rapid increase of AI contribution in cardiovascular imaging techiniques is expected in the near future. 3D RV acquisition is feasible in the majority of subjects, although the quality of imaging and appropriate echocardiographic views remains operator - depended. Reference values of 3D RV volumes and 3D - STE systolic function indices were obtained by advanced technology AI software. Larger studies are required to establish normal values for the above indices.

P-1050. A Decade of Pneumocystis jirovecii Pneumonia: a Single-Center Retrospective Analysis in Both HIV and Non-HIV Populations

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic disease, commonly occurring in individuals with human immunodeficiency virus (HIV) or immunodepression. This study analyzes PJP cases in our local setting, detailing the epidemiological and clinical characteristics, as well as prognosis, and underlying diseases. Methods Retrospective analysis of adult inpatient PJP cases (2014-2023). Diagnosis was presumptive (epidemiological, clinical, and imaging findings), or confirmed microbiologically. Statistical analysis utilized the chi-square test. Results Forty-two patients were identified: 66% male, median age of 47.5 years [25-83]. Seventy-four percent were HIV positive, with a median CD4+ count of 35 [1-347]. All had detectable HIV viral load, except one (suppressed for years, but with a new diagnosis of neoplasm). Non-HIV patients (26%) underlying diseases included hematological (n=6) or solid-organ malignancies (n=1), autoimmune diseases under corticosteroid therapy (n=2), pulmonary interstitial disease (n=1), and granulomatous systemic disease under investigation (n=1). Eighty-six percent had peripheral lymphopenia at diagnosis, and only one patient was receiving regular prophylaxis. The incidence of non-HIV patients significantly increased in the latter 5 years (5.5% vs 42%, p=0.008). Diagnosis was confirmed by positive direct antibody fluorescence staining in half of the patients. No molecular biology techniques or B-D-glucan assays were available. Seventeen (40%) patients required admission to level II or III units, of which 23% required invasive mechanical ventilation and 35% high-flow oxygen. Treatment included cotrimoxazole (n=40) and atovaquone (n=2). One-third of patients had cytomegalovirus reactivation, requiring antiviral therapy. Non-HIV patient mortality was significantly higher than HIV patients (45% vs 13%, p=0.023). Fifteen percent of survivors were readmitted within 30 days. Conclusion The epidemiology of PJP is evolving, with a noticeable increase in non-HIV cases, which are associated with significantly higher mortality despite appropriate treatment. Authors emphasize the importance of identifying new risk groups for chemoprophylaxis to improve prognosis. Disclosures All Authors: No reported disclosures

P-596. Immunobridging Demonstrating Effectiveness of the Bivalent Respiratory Syncytial Virus (RSV) Prefusion F Subunit Vaccine in Adults 18-59 Years of Age at High Risk of Severe RSV Disease in a Phase 3 Trial: The C3671023 MONeT Study Results

Abstract Background C3671023 Substudy A (NCT05842967) is a phase 3, randomized, double-blinded, placebo-controlled study to assess the safety and immunogenicity of Pfizer’s RSVpreF in adults 18-59 years of age at high risk of severe RSV disease due to chronic medical conditions, including pulmonary, cardiovascular, hepatic, renal, and metabolic (including diabetes mellitus) disorders. Primary objectives were to assess safety and to demonstrate a non-inferior immune response in adults 18-59 years of age at high risk of severe RSV disease compared to adults age ≥ 60 from the pivotal phase 3 C3671013 study which demonstrated efficacy against RSV Lower Respiratory Tract Illness (LRTI).Table 1:Number of Participants Reporting at Least 1 Adverse Event (Excluding Prespecified Events) for Each Analysis Interval After Vaccination with RSVpreF Methods Participants were randomized 2:1 to receive 1 dose of RSVpreF or placebo (453 RSVpreF: 225 placebo). Sera collected before and at 1 month after vaccination were tested concurrently with sera collected from ∼400 RSVpreF recipients from the C3671013 study. Reactogenicity events were collected for 7 days following vaccination. Adverse events (AEs) were collected through 1 month following vaccination; adverse events of special interest (AESIs), newly diagnosed chronic medical conditions (NDCMCs), and serious AEs were collected throughout the study. Non-inferiority (NI) would be declared if the lower bounds of the 95% confidence interval (CI) of adjusted Geometric Mean Ratio (GMR) of neutralizing titers (NTs) were > 0.667 and lower bounds of the 95% CI of seroresponse rate differences were > -10% for RSV A and RSV B.Table 2:Comparison of Model-Adjusted RSV Neutralizing - GMTs at 1 Month After Vaccination with RSVpreF- 18 Through 59 Years at High Risk (C3671023) versus 60 Years and Older (C3671013) Results Proportions of participants with local reactions were higher in the RSVpreF group; systemic events were generally similar in both groups (Figure 1). Proportions of participants reporting any AEs were similar between RSVpreF and placebo through 1 month following vaccination and throughout the study (Table 1). RSV A and RSV B NTs 1 month after RSVpreF vaccination in adults 18-59 years of age at high risk were non-inferior to adults ≥ 60 years of age (Table 2). NI was met for seroresponse rates (Table 3).Table 3:Comparison of RSV Neutralizing Titer Seroresponse Rates 1 Month After Vaccination with RSVpreF- 18 Through 59 Years at High Risk (C3671023) versus 60 Years and Older (C3671013) Conclusion RSVpreF was well-tolerated with no safety concerns and demonstrated immunobridging to efficacy in adults 18-59 years of age at high risk of severe RSV disease compared to adults age ≥ 60. Results support the use of RSVpreF among adults 18-59 years of age with high-risk conditions to prevent RSV LRTI.Figure 1:Local Reactions and Systemic Events Reported, By Maximum Severity, Within 7 Days After Vaccination with RSVpreF Disclosures William Towner, MD, GSK: Grant/Research Support|Janssen: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Elliot N. DeHaan, MD, Pfizer, Inc.: Salaried employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Qin Jiang, PhD, Pfizer: Salary|Pfizer: Stocks/Bonds (Public Company) Wen Li, PhD, Pfizer: stipend for my employment|Pfizer: Stocks/Bonds (Public Company) Farah Rahman, DO, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Michael Patton, B.Sc., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Hayley Wyper, BBiomedSc, Pfizer: Stocks/Bonds (Public Company) Maria Maddalena Lino, PhD, Pfizer: Stocks/Bonds (Private Company) Uzma N. Sarwar, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Elena Kalinina, PhD, Pfizer, Inc.: Salary|Pfizer, Inc.: Stocks/Bonds (Public Company) David Cooper, PhD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Kena A. Swanson, Ph.D., Pfizer: Employee of Pfizer|Pfizer: Stocks/Bonds (Public Company) Annaliesa S. Anderson, PhD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Alejandra C. Gurtman, M.D., Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Iona Munjal, MD, Pfizer: Salaried employee|Pfizer: Stocks/Bonds (Public Company)

Additive value of simultaneous exercise echocardiography to cardiopulmonary exercise testing in unexplained dyspnea

Abstract Background/Introduction Exertional dyspnea is a nonspecific symptom and frequently serves as the initial sign of numerous cardiac and non-cardiac illnesses. Cardiopulmonary exercise testing (CPET) is often used in the workup of dyspnea, but specific markers for cardiac and peripheral causes of dyspnea are lacking. Combining CPET with exercise echocardiography (CPETecho) can non-invasively identify all pathophysiological mechanisms limiting exercise capacity, including cardiac, pulmonary, and peripheral disorders. Purpose To evaluate the use of CPETecho in patients with unexplained exertional dyspnea compared to CPET alone. Methods In this retrospective observational study, we evaluated patients with unexplained dyspnea (normal resting echocardiography and normal lung function) who underwent CPETecho at two university hospitals between July 2021 and November 2023. CPETecho was conducted on a semi-supine bicycle ergometer. At rest, submaximal exercise (heart rate ±100 bpm) and peak exercise echocardiography was performed. Respiratory gases, heart rate, and electrocardiogram were recorded continuously. We evaluated limitations to exercise according to cutoffs in published literature and compared them to diagnoses obtained via CPET alone, with exercise echo values being blinded. CPET reports were interpreted by 3 independent reviewers with expertise in cardiac rehabilitation and consensus was obtained. Results We enrolled 123 patients (63% women, mean age 67 ± 12 years). CPETecho identified a cause for dyspnea in 101 patients (81%), compared to 87 patients (71%) with CPET alone. However, only 36 patients (29%) had a ‘certain and complete’ diagnosis using CPET alone. CPET alone missed a diagnosis in 48% of patients, most commonly missing heart failure with preserved ejection fraction (HFpEF 27%), exercise pulmonary hypertension (20%) and LV or RV systolic dysfunction (20 and 20% respectively). Twenty eight patients were deemed to have a normal test by CPET, however CPETecho identified a cause for dyspnea in 89% of these patients, mainly cardiac disorders. Conclusion In summary, our study emphasizes the value of CPETecho in assessing patients with exertional dyspnea. CPETecho offers superior diagnostic accuracy compared to CPET alone, specifically aiding in the identification of cardiac disorders.