Multidisciplinary Approach to Chronic Thromboembolic Pulmonary Hypertension: Role of Radiologists.

Management of chronic thromboembolic pulmonary hypertension (CTEPH) should be determined by a multidisciplinary team, ideally at a specialized CTEPH referral center. Radiologists contribute to this multidisciplinary process by helping to confirm the diagnosis of CTEPH and delineating the extent of disease, both of which help determine a treatment decision. Preoperative assessment of CTEPH usually employs multiple imaging modalities, including ventilation-perfusion (V/Q) scanning, echocardiography, CT pulmonary angiography (CTPA), and right heart catheterization with pulmonary angiography. Accurate diagnosis or exclusion of CTEPH at imaging is imperative, as this remains the only form of pulmonary hypertension that is curative with surgery. Unfortunately, CTEPH is often misdiagnosed at CTPA, which can be due to technical factors, patient-related factors, radiologist-related factors, as well as a host of disease mimics including acute pulmonary embolism, in situ thrombus, vasculitis, pulmonary artery sarcoma, and fibrosing mediastinitis. Although V/Q scanning is thought to be substantially more sensitive for CTEPH compared with CTPA, this is likely due to lack of recognition of CTEPH findings rather than a modality limitation. Preoperative evaluation for pulmonary thromboendarterectomy (PTE) includes assessment of technical operability and surgical risk stratification. While the definitive therapy for CTEPH is PTE, other minimally invasive or noninvasive therapies also lead to clinical improvements including greater survival. Complications of PTE that can be identified at postoperative imaging include infection, reperfusion edema or injury, pulmonary hemorrhage, pericardial effusion or hemopericardium, and rethrombosis. ©RSNA, 2022 Online supplemental material is available for this article.

Airway-Occluding Mucus Plugs and Mortality in Patients With Chronic Obstructive Pulmonary Disease.

Importance: Airway mucus plugs are common in patients with chronic obstructive pulmonary disease (COPD); however, the association of airway mucus plugging and mortality in patients with COPD is unknown. Objective: To determine whether airway mucus plugs identified on chest computed tomography (CT) were associated with increased all-cause mortality. Design, Setting, and Participants: Observational retrospective analysis of prospectively collected data of patients with a diagnosis of COPD in the Genetic Epidemiology of COPD cohort. Participants were non-Hispanic Black or White individuals, aged 45 to 80 years, who smoked at least 10 pack-years. Participants were enrolled at 21 centers across the US between November 2007 and April 2011 and were followed up through August 31, 2022. Exposures: Mucus plugs that completely occluded airways on chest CT scans, identified in medium- to large-sized airways (ie, approximately 2- to 10-mm lumen diameter) and categorized as affecting 0, 1 to 2, or 3 or more lung segments. Main Outcomes and Measures: The primary outcome was all-cause mortality, assessed with proportional hazard regression analysis. Models were adjusted for age, sex, race and ethnicity, body mass index, pack-years smoked, current smoking status, forced expiratory volume in the first second of expiration, and CT measures of emphysema and airway disease. Results: Among the 4483 participants with COPD, 4363 were included in the primary analysis (median age, 63 years [IQR, 57-70 years]; 44% were women). A total of 2585 (59.3%), 953 (21.8%), and 825 (18.9%) participants had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. During a median 9.5-year follow-up, 1769 participants (40.6%) died. The mortality rates were 34.0% (95% CI, 32.2%-35.8%), 46.7% (95% CI, 43.5%-49.9%), and 54.1% (95% CI, 50.7%-57.4%) in participants who had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively. The presence of mucus plugs in 1 to 2 vs 0 and 3 or more vs 0 lung segments was associated with an adjusted hazard ratio of death of 1.15 (95% CI, 1.02-1.29) and 1.24 (95% CI, 1.10-1.41), respectively. Conclusions and Relevance: In participants with COPD, the presence of mucus plugs that obstructed medium- to large-sized airways was associated with higher all-cause mortality compared with patients without mucus plugging on chest CT scans.

Three-Dimensional Pressure Profile of the Lower Esophageal Sphincter and Crural Diaphragm in Patients with Achalasia Esophagus.

BACKGROUND & AIMS: Smooth muscles of the lower esophageal sphincter (LES) and skeletal muscle of the crural diaphragm (esophagus hiatus) provide the sphincter mechanisms at the esophagogastric junction (EGJ). We investigated differences in the 3-dimensional (3D) pressure profile of the LES and hiatal contraction between healthy subjects and patients with achalasia esophagus. METHODS: We performed a prospective study of 10 healthy subjects (controls; 7 male; mean age, 60 ± 15 years; mean body mass index, 25 ± 2) and 12 patients with a diagnosis of achalasia (7 male; mean age, 63 ± 13 years; mean body mass index, 26 ± 1), enrolled at a gastroenterology clinic. Participants underwent 3D high-resolution manometry (3DHRM) with a catheter equipped with 96 transducers (for the EGJ pressure recording). A 0.5-mm metal ball was taped close to the transducer number 1 of the 3DHRM catheter. EGJ pressure was recorded at end-expiration (LES pressure) and at the peak of forced inspiration (hiatal contraction). Computed tomography (CT) scans were performed to localize the circumferential location of the metal ball on the catheter. Esophagus, LES, stomach, right and left crus of the diaphragm, and spine were segmented in each CT scan slice images to construct the 3D morphology of the region. RESULTS: The metal ball was located at the 7 o'clock position in all controls. The circumferential orientation of metal ball was displaced 45 to 90 degrees in patients with achalasia compared with controls. The 3D-pressure profile of the EGJ at end-expiration and forced inspiration revealed marked differences between the groups. The LES turns to the left as it entered from the chest into the abdomen, forming an angle between the spine and LES. The spine-LES angle was smaller in patients with achalasia (104°) compared with controls (124°). Five of the 10 subjects with achalasia had physical breaks in the left crus of the diaphragm CONCLUSIONS: Besides LES, the 3D pressure profile of the EGJ can indicate anatomic and functional abnormalities of the crural diaphragm muscle in patients with achalasia esophagus. Further studies are needed to define the nature of hiatal and crural diaphragm dysfunction in patients with achalasia of the esophagus.

Intimal Sarcoma of the Great Vessels.

Intimal sarcomas of the pulmonary artery and aorta are rare entities with a poor prognosis. In many instances, pulmonary artery sarcomas are misinterpreted as acute or chronic pulmonary thromboembolism, whereas aortic intimal sarcomas are often misdiagnosed as protuberant atherosclerotic disease or intimal thrombus. Discernment of intimal sarcomas from these and other common benign entities is essential for the timely initiation of aggressive therapy. The most useful imaging modalities for assessment of a suspected intimal sarcoma include CT angiography, fluorine 18-fluorodeoxyglucose PET, and MRI. The authors discuss the clinical features, current treatment options, characteristic imaging findings, and underlying pathologic features of intimal sarcomas. The authors emphasize imaging discernment of intimal sarcomas and how their differential diagnosis is informed by knowledge of radiologic-pathologic correlation. The most reliable distinguishing imaging features are also emphasized to improve accurate and timely diagnosis. Online supplemental material is available for this article. ©RSNA, 2021.

Ischemic Heart Disease: Noninvasive Imaging Techniques and Findings.

Ischemic heart disease is a leading cause of death worldwide and comprises a large proportion of annual health care expenditure. Management of ischemic heart disease is now best guided by the physiologic significance of coronary artery stenosis. Invasive coronary angiography is the standard for diagnosing coronary artery stenosis. However, it is expensive and has risks including vascular access site complications and contrast material-induced nephropathy. Invasive coronary angiography requires fractional flow reserve (FFR) measurement to determine the physiologic significance of a coronary artery stenosis. Multiple noninvasive cardiac imaging modalities can also anatomically delineate or functionally assess for significant coronary artery stenosis, as well as detect the presence of myocardial infarction (MI). While coronary CT angiography can help assess the degree of anatomic stenosis, its inability to assess the physiologic significance of lesions limits its specificity. Physiologic significance of coronary artery stenosis can be determined by cardiac MR vasodilator or dobutamine stress imaging, CT stress perfusion imaging, FFR CT, PET myocardial perfusion imaging (MPI), SPECT MPI, and stress echocardiography. Clinically unrecognized MI, another clear indicator of physiologically significant coronary artery disease, is relatively common and is best evaluated with cardiac MRI. The authors illustrate the spectrum of imaging findings of ischemic heart disease (coronary artery disease, myocardial ischemia, and MI); highlight the advantages and disadvantages of the various noninvasive imaging methods used to assess ischemic heart disease, as illustrated by recent clinical trials; and summarize current indications and contraindications for noninvasive imaging techniques for detection of ischemic heart disease. Online supplemental material is available for this article. Published under a CC BY 4.0 license.

Use of a Dual Artificial Intelligence Platform to Detect Unreported Lung Nodules.

OBJECTIVE: To investigate the performance of Dual-AI Deep Learning Platform in detecting unreported pulmonary nodules that are 6 mm or greater, comprising computer-vision (CV) algorithm to detect pulmonary nodules, with positive results filtered by natural language processing (NLP) analysis of the dictated report. METHODS: Retrospective analysis of 5047 chest CT scans and corresponding reports. Cases which were both CV algorithm positive (nodule ≥ 6 mm) and NLP negative (nodule not reported), were outputted for review by 2 chest radiologists. RESULTS: The CV algorithm detected nodules that are 6 mm or greater in 1830 (36.3%) of 5047 cases. Three hundred fifty-five (19.4%) were unreported by the radiologist, as per NLP algorithm. Expert review determined that 139 (39.2%) of 355 cases were true positives (2.8% of all cases). One hundred thirty (36.7%) of 355 cases were unnecessary alerts-vague language in the report confounded the NLP algorithm. Eighty-six (24.2%) of 355 cases were false positives. CONCLUSIONS: Dual-AI platform detected actionable unreported nodules in 2.8% of chest CT scans, yet minimized intrusion to radiologist's workflow by avoiding alerts for most already-reported nodules.

Imaging Findings of Vaping-Associated Lung Injury.

To listen to the podcast associated with this article, please select one of the following: iTunes or Google Play. OBJECTIVE. E-cigarettes are devices that aerosolize nicotine- or cannabis-based concentrates mixed with other solvents and have been marketed as an alternative to cigarettes. E-cigarette use, or vaping, is increasingly popular but has not been proven to be an innocuous substitute for traditional smoking. Several patterns of vaping-associated inhalational lung injuries have been reported in the past few years. This article reviews many of the imaging patterns that have been encountered in association with e-cigarette use. CONCLUSION. E-cigarette use is associated with a range of lung injury patterns that have only recently been recognized as use of these products continues to rise. When the radiologist sees one of these patterns of lung injury, it is important to raise the possibility of vaping-induced lung injury because cessation of vaping is an important step in treatment.

Chest CT and Coronavirus Disease (COVID-19): A Critical Review of the Literature to Date.

OBJECTIVE. Coronavirus disease (COVID-19) is a global pandemic. Studies in the radiology literature have suggested that CT might be sufficiently sensitive and specific in diagnosing COVID-19 when used in lieu of a reverse transcription-polymerase chain reaction test; however, this suggestion runs counter to current society guidelines. The purpose of this article is to critically review some of the most frequently cited studies on the use of CT for detecting COVID-19. CONCLUSION. To date, the radiology literature on COVID-19 has consisted of limited retrospective studies that do not substantiate the use of CT as a diagnostic test for COVID-19.

Spectrum of Coronary Artery Aneurysms: From the Radiologic Pathology Archives.

Advances in medical diagnosis reveal that coronary artery aneurysms (CAAs) may develop in several clinical scenarios and manifest variable symptoms, imaging appearances, and outcomes. Aneurysms are pathologically classified into three groups: atherosclerotic, inflammatory, and noninflammatory. The last category is associated with congenital, inherited, and connective tissue disorders. Overlap exists among the groups, because secondary atherosclerotic change may be present in an aneurysm of any cause. Atherosclerosis is the most common cause of CAAs in adults, and inflammation is considered the underlying mechanism. In children, Kawasaki disease is the most likely cause of CAAs. In both conditions, the aneurysms are usually multiple and affect more than one coronary artery. Mycotic (infectious), iatrogenic, and cocaine-induced CAAs are also well documented. Most CAAs are discovered incidentally, but potential cardiovascular complications include thrombosis, occlusion, fistula formation, rupture, myocardial infarction, and cardiac tamponade. Imaging modalities to evaluate a suspected CAA include transthoracic echocardiography, angiographic cardiac catheterization, electrocardiographically gated computed tomographic angiography, cardiac magnetic resonance (MR) imaging, and MR angiography. Management is usually individualized, and options include surveillance, anticoagulant therapy, percutaneous stent or coil placement, surgical resection, and coronary artery bypass grafting.

Noncontrast-enhanced peripheral venography using velocity-selective magnetization preparation and transient balanced SSFP.

PURPOSE: To develop a three-dimensional (3D) noncontrast-enhanced (NCE) peripheral magnetic resonance venography (MRV) method and demonstrate its feasibility in vivo. METHODS: The proposed MRV pulse sequence consisted of a velocity-selective (VS) inversion preparation module, inversion delay time (TI), fat inversion pulse, and 3D balanced steady-state free precession (bSSFP) dummy excitations and readout. The VS preparation module inverted arterial blood, which recovered close to zero magnetization during TI. The TI and the number of dummy excitations (Nnum ) were numerically optimized for maximizing vein-to-background contrast and tested in a healthy subject. The proposed MRV of the entire peripheral system, using four-station acquisition, was performed in six healthy subjects and three peripheral artery patients. RESULTS: The numerical optimization yielded TI = 350 ms and Ndum = 40, which was supported by the largest vein contrast among the parameters chosen around the optima on in vivo venograms. Four-station peripheral MRV using the optimized parameters well visualized all major deep veins with high vein-to-background contrast. The relative vein contrast ratios were 0.80 ± 0.08, 0.75 ± 0.07, and 0.84 ± 0.06 against the arteries, muscle, and fat, respectively. CONCLUSION: The proposed NCE MRV using VS preparation and transient bSSFP can generate high-contrast peripheral venograms directly with a single acquisition.

Castleman Disease of the Thorax: Clinical, Radiologic, and Pathologic Correlation: From the Radiologic Pathology Archives.

Castleman disease is a complex lymphoproliferative disease pathologically divided into two subtypes, the hyaline vascular variant (HVV) and the plasma cell variant (PCV). The HVV is the most common, is thought to represent a benign neoplasm of lymph node stromal cells, and is treated with surgical resection. It is most commonly found in the mediastinum, where it classically appears as a unicentric, avidly enhancing mass at computed tomography (CT) and magnetic resonance imaging. This appearance can mimic other avidly enhancing mediastinal masses, and location, clinical history, laboratory data, and nuclear medicine single photon emission CT (SPECT) and positron emission tomography (PET) studies can help narrow the differential diagnosis. Multicentric Castleman disease (MCD), which in the majority of cases is composed of the PCV, is an aggressive lymphoproliferative disorder associated with human herpesvirus infection, interleukin 6 dysregulation, and other systemic disorders. While it can be difficult to differentiate MCD from lymphoma, the presence of avidly enhancing lymph nodes can suggest the diagnosis. The purpose of this article is to review the clinical, immunologic, and pathologic findings associated with both unicentric Castleman disease and MCD and discuss how the imaging findings correlate with the pathophysiology of the disease.

Mosaic Attenuation: Etiology, Methods of Differentiation, and Pitfalls.

Mosaic attenuation is a commonly encountered pattern on computed tomography that is defined as heterogeneous areas of differing lung attenuation. This heterogeneous pattern of attenuation is the result of diverse causes that include diseases of the small airways, pulmonary vasculature, alveoli, and interstitium, alone or in combination. Small airways disease can be a primary disorder, such as respiratory bronchiolitis or constrictive bronchiolitis, or be part of parenchymal lung disease, such as hypersensitivity pneumonitis, or large airways disease, such as bronchiectasis and asthma. Vascular causes resulting in mosaic attenuation are typically chronic thromboembolic pulmonary hypertension, which is characterized by organizing thrombi in the elastic pulmonary arteries, or pulmonary arterial hypertension, a heterogeneous group of diseases affecting the distal pulmonary arterioles. Diffuse ground-glass opacity can result in a mosaic pattern related to a number of processes in acute (eg, infection, pulmonary edema), subacute (eg, organizing pneumonia), or chronic (eg, fibrotic diseases) settings. Imaging clues that can assist the radiologist in pinpointing a diagnosis include evidence of large airway involvement, cardiovascular abnormalities, septal thickening, signs of fibrosis, and demonstration of airtrapping at expiratory imaging.

Aortic arch dissection: a controversy of classification.

Aortic dissections originating in the ascending aorta and descending aorta have been classified as type A and type B dissections, respectively. However, dissections with intimal flap extension into the aortic arch between the innominate and left subclavian arteries are not accounted for adequately in the widely used Stanford classification. This gap has been the subject of controversy in the medical and surgical literature, and there is a tendency among many radiologists to categorize such arch dissections as type A lesions, thus making them an indication for surgery. However, the radiologic perspective is not supported by either standard dissection classification or current clinical management. In this special report, the origin of dissection classification and its evolution into current radiologic interpretation and surgical practice are reviewed. The cause for the widespread misconception about classification and treatment algorithms is identified. Institutional review board approval and waiver of informed consent were obtained as part of this HIPAA-compliant retrospective study to assess all aortic dissection studies performed at the University of Maryland Medical Center, Baltimore between 2010 and 2012 to determine the prevalence of arch dissections. Finally, a unified classification system that reconciles imaging interpretation and management implementation is proposed.

Missed pulmonary embolism on abdominal CT.

OBJECTIVE: The purpose of this study is to evaluate a series of missed pulmonary emboli (PE) identified on abdominal CT and to describe their characteristics and the clinical scenario. MATERIALS AND METHODS: All reports of chest CT scans performed during a 12-month period were searched for keywords indicative of PE. Among patients with PE, patients who also underwent an enhanced abdominal CT within 3 months were assessed for missed PE. Three radiologists reviewed the abdominal CT to confirm the presence of a missed PE. Missed PEs were classified as unknown or known. Each study was assessed for characteristics of the missed PE and the image quality of the PE study. The electronic medical record was used to document the clinical context in which the PE occurred. RESULTS: Eighteen patients (12 men and six women; average age, 58.8 years) were identified as having missed PE on abdominal CT. In seven patients (38.9%), the PE had not been previously diagnosed. Most of the missed PEs were segmental, but three missed PEs occurred in lobar vessels. In a slight majority of the cases, the reviewing radiologists judged the contrast bolus as good. The abdominal CT on which PE was overlooked was obtained for a variety of reasons, most commonly because of abdominal pain or to follow up a preexisting condition. CONCLUSION: This study shows that missed PE can occur on abdominal CT. It is recommended that interpretation include a careful search of the lower pulmonary arterial vasculature on contrast-enhanced abdominal CT scans.

Missed pulmonary emboli on CT angiography: assessment with pulmonary embolism-computer-aided detection.

OBJECTIVE: The purpose of this study is to assess the use of a pulmonary embolism (PE)- computer-aided detection (CADx) program in the detection of PE missed in clinical practice. MATERIALS AND METHODS: Pulmonary CT angiography (CTA) studies (n = 6769) performed between January 2009 and July 2012 were retrospectively assessed by a thoracic radiologist. In studies that were positive for PE, all prior contrast-enhanced pulmonary CTA studies were reviewed. Missed PE was deemed to have occurred if PE was not described in the final interpretation. The presence, proximal extent, and number of PEs were agreed on by three thoracic radiologists. Studies with missed acute PE and available slice thickness of 2 mm or less were assessed with a prototype PE-CADx program. False-positive PE-CADx marks were analyzed. Outcomes of missed acute PEs were assessed in patients with both follow-up imaging and clinical data. RESULTS: Fifty-three studies with overlooked acute PE met our inclusion criteria for PE-CADx assessment. The PE-CADx program identified at least one PE in 77.4% of instances (41/53). PE-CADx correctly marked at least one PE in 23 of 23 cases (100%) with multiple PEs and 18 of 30 (60%) cases with a solitary PE (p < 0.001). PE-CADx per-study sensitivity was significantly higher for segmental (65.5%) than for subsegmental (91.7%) PEs (p = 0.002). PE-CADx averaged 3.8 false-positive marks per case (range, 0-23 marks). Fourteen patients with missed PE who were not receiving anticoagulation therapy developed new PEs, including nine with an isolated subsegmental PE on the initial CT scan. CONCLUSION: PE-CADx correctly identified 77.4% of cases of acute PE that were previously missed in clinical practice.

From the radiologic pathology archives: organization and fibrosis as a response to lung injury in diffuse alveolar damage, organizing pneumonia, and acute fibrinous and organizing pneumonia.

Organization, characterized by fibroblast proliferation, is a common and nearly universal response to lung injury whether it is focal or diffuse. Despite the vast range of injurious agents, the lung's response to injury is quite limited, with a similar pattern of reaction seen radiologically and histologically regardless of the underlying cause. Although there is a tendency to divide organization into distinct entities, the underlying injury to the alveolar epithelial basement membrane is a uniting factor in these processes. This pattern of lung injury is seen in the organizing phase of diffuse alveolar damage, organizing pneumonia (OP), acute fibrinous and organizing pneumonia, and certain types of fibrotic lung disease. In addition, although organization can heal without significant injury, in some instances it progresses to fibrosis, which can be severe. When fibrosis due to organization is present, other histologic and imaging patterns, such as those seen in nonspecific interstitial pneumonia, can develop, reflecting that fibrosis can be a sequela of organization. This article reviews the histologic and radiologic findings of organization in lung injury due to diffuse alveolar damage, OP, and acute fibrinous and organizing pneumonia and helps radiologists understand that the histologic and radiologic findings depend on the degree of injury and the subsequent healing response.

Excipient Lung Disease in a Patient with Preexisting Chronic Thromboembolic Disease.

Excipient lung disease is an uncommon condition that occurs when crushed oral tablets are injected intravenously and cause pulmonary hypertension. Diagnosis requires a high degree of clinical suspicion and recognition of characteristic imaging findings. The authors present a previously unreported combination of findings in a patient with excipient lung disease and preexisting chronic thromboembolic disease. A pattern of diffuse centrilobular nodules with sparing of lung segments with chronically occluded pulmonary arteries was highly suggestive of the diagnosis and indicated a vascular cause. Pathologic specimen obtained at the time of pulmonary thromboendarterectomy helped confirm the clinically suspected entity. Keywords: Pulmonary Arteries, Embolism/Thrombosis, Foreign Bodies, Lung Supplemental material is available for this article. © RSNA, 2023.

Silent Airway Mucus Plugs in COPD and Clinical Implications.

BACKGROUND: Airway mucus plugs are frequently identified on CT scans of patients with COPD with a smoking history without mucus-related symptoms (ie, cough, phlegm [silent mucus plugs]). RESEARCH QUESTION: In patients with COPD, what are the risk and protective factors associated with silent airway mucus plugs? Are silent mucus plugs associated with functional, structural, and clinical measures of disease? STUDY DESIGN AND METHODS: We identified mucus plugs on chest CT scans of participants with COPD from the COPDGene study. The mucus plug score was defined as the number of pulmonary segments with mucus plugs, ranging from 0 to 18, and categorized into three groups (0, 1-2, and ≥ 3). We determined risk and protective factors for silent mucus plugs and the associations of silent mucus plugs with measures of disease severity using multivariable linear and logistic regression models. RESULTS: Of 4,363 participants with COPD, 1,739 had no cough or phlegm. Among the 1,739 participants, 627 (36%) had airway mucus plugs identified on CT scan. Risk factors of silent mucus plugs (compared with symptomatic mucus plugs) were older age (OR, 1.02), female sex (OR, 1.40), and Black race (OR, 1.93) (all P values < .01). Among those without cough or phlegm, silent mucus plugs (vs absence of mucus plugs) were associated with worse 6-min walk distance, worse resting arterial oxygen saturation, worse FEV1 % predicted, greater emphysema, thicker airway walls, and higher odds of severe exacerbation in the past year in adjusted models. INTERPRETATION: Mucus plugs are common in patients with COPD without mucus-related symptoms. Silent mucus plugs are associated with worse functional, structural, and clinical measures of disease. CT scan-identified mucus plugs can complement the evaluation of patients with COPD.

Intramyocardial cell-based therapy with Lomecel-B during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome: the ELPIS phase I trial.

Aims: Hypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction of the right ventricle (RV) to provide systemic circulation. This substantially increases the RV load, wall stress, maladaptive remodelling, and dysfunction, which in turn increases the risk of death or transplantation. Methods and results: We conducted a phase 1 open-label multicentre trial to assess the safety and feasibility of Lomecel-B as an adjunct to second-stage HLHS surgical palliation. Lomecel-B, an investigational cell therapy consisting of allogeneic medicinal signalling cells (MSCs), was delivered via intramyocardial injections. The primary endpoint was safety, and measures of RV function for potential efficacy were obtained. Ten patients were treated. None experienced major adverse cardiac events. All were alive and transplant-free at 1-year post-treatment, and experienced growth comparable to healthy historical data. Cardiac magnetic resonance imaging (CMR) suggested improved tricuspid regurgitant fraction (TR RF) via qualitative rater assessment, and via significant quantitative improvements from baseline at 6 and 12 months post-treatment (P < 0.05). Global longitudinal strain (GLS) and RV ejection fraction (EF) showed no declines. To understand potential mechanisms of action, circulating exosomes from intramyocardially transplanted MSCs were examined. Computational modelling identified 54 MSC-specific exosome ribonucleic acids (RNAs) corresponding to changes in TR RF, including miR-215-3p, miR-374b-3p, and RNAs related to cell metabolism and MAPK signalling. Conclusion: Intramyocardially delivered Lomecel-B appears safe in HLHS patients and may favourably affect RV performance. Circulating exosomes of transplanted MSC-specific provide novel insight into bioactivity. Conduct of a controlled phase trial is warranted and is underway.Trial registration number NCT03525418.