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Context.—: Cardiac and pulmonary allograft recipients represent a unique population, frequently interacting with support groups and exhibiting intense curiosity about their pathology. Like other solid organ transplant patients, they have enduring and frequent interaction with the laboratory for routine allograft surveillance., Objective.—: To address patient requests to understand what happens to their explanted organ and to better understand their disease while simultaneously improving awareness of pathologists' role in their continuing care., Design.—: At routine follow-up appointments, transplant nurse coordinators offer each allograft recipient the opportunity to interact with a pathologist in our "On My Path" program. Organ viewing occurs in a private setting, in a specialized room. Relevant pathology is discussed, and questions are answered, with documentation in the medical record. The patient is subsequently gifted a 3-dimensional model of their explanted organ. Transplant coordinators were surveyed for their feedback on the experience., Results.—: One hundred fifty-eight interactions have been documented (2017-2022), including patients who underwent cardiac transplant (96, 61%), single or bilateral lung transplant (54, 34%), or combination lung and heart transplant (8, 5%). Transplant coordinators reported an increase in patient understanding of their disease and emotional closure related to the disease through the On My Path program., Conclusions.—: Pathologists providing direct patient care is a feasible model that addresses currently unmet desires of the transplant population to better understand their pathology. Providing a 3-dimensional model helps to empower patients and drives satisfaction. These interactions also improve awareness about pathology as a discipline and its importance in the continued care of transplant recipients., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Electron microscopy (EM) was a popular diagnostic tool in the 1970s and early 80s. With the adoption of newer, less expensive techniques, such as immunohistochemistry, the role of EM in diagnostic surgical pathology has dwindled substantially. Nowadays, even in academic centers, EM interpretation is relegated to renal pathologists and the handful of (aging) pathologists with experience using the technique. As such, EM interpretation is truly arcane-understood by few and mysterious to many. Nevertheless, there remain situations in which EM is the best or only ancillary test to ascertain a specific diagnosis. Thus, there remains a critical need for the younger generation of surgical pathologists to learn EM interpretation. Recognizing this need, cardiac EM was made the theme of the Cardiovascular Evening Specialty Conference at the 2023 United States and Canadian Academy of Pathology (USCAP) annual meeting in New Orleans, Louisiana. Each of the speakers contributed their part to this article, the purpose of which is to review EM as it pertains to myocardial tissue and provide illustrative examples of the spectrum of ultrastructural cardiac pathology seen in storage/metabolic diseases, cardiomyopathies, infiltrative disorders, and cardiotoxicities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole-slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool., Methods: Consecutive bile duct brushing WSIs from indeterminate strictures were obtained. A multidisciplinary panel reviewed all relevant information and provided a central interpretation for each WSI as being "positive," "negative," or "indeterminate." The WSIs were then uploaded to the AI application. The AI scored each WSI as positive or negative for malignancy (i.e., computer-aided diagnosis [CADx]). For each WSI, the AI prioritized cytologic tiles by the likelihood that malignant material was present in the tile. Via the AI, blinded cytologists reviewed all WSIs and provided interpretations (i.e., computer-aided detection [CADe]). The diagnostic accuracies of the WSI evaluation via CADx, CADe, and the original clinical cytologic interpretation (official cytologic interpretation [OCI]) were compared., Results: Of the 84 WSIs, 15 were positive, 42 were negative, and 27 were indeterminate after central review. The WSIs generated on average 141,950 tiles each. Cytologists using the AI evaluated 10.5 tiles per WSI before making an interpretation. Additionally, cytologists required an average of 84.1 s of total WSI evaluation. WSI interpretation accuracies for CADx (0.754; 95% CI, 0.622-0.859), CADe (0.807; 95% CI, 0.750-0.856), and OCI (0.807; 95% CI, 0.671-0.900) were similar., Conclusions: This trial demonstrates that an AI application allows cytologists to perform a triaged review of WSIs while maintaining accuracy., (© 2024 American Cancer Society.)

Heart failure with preserved ejection fraction (HFpEF) is a major, worldwide health-care problem. Few therapies for HFpEF exist because the pathophysiology of this condition is poorly defined and, increasingly, postulated to be diverse. Although perturbations in other organs contribute to the clinical profile in HFpEF, altered cardiac structure, function or both are the primary causes of this heart failure syndrome. Therefore, studying myocardial tissue is fundamental to improve pathophysiological insights and therapeutic discovery in HFpEF. Most studies of myocardial changes in HFpEF have relied on cardiac tissue from animal models without (or with limited) confirmatory studies in human cardiac tissue. Animal models of HFpEF have evolved based on theoretical HFpEF aetiologies, but these models might not reflect the complex pathophysiology of human HFpEF. The focus of this Review is the pathophysiological insights gained from studies of human HFpEF myocardium. We outline the rationale for these studies, the challenges and opportunities in obtaining myocardial tissue from patients with HFpEF and relevant comparator groups, the analytical approaches, the pathophysiological insights gained to date and the remaining knowledge gaps. Our objective is to provide a roadmap for future studies of cardiac tissue from diverse cohorts of patients with HFpEF, coupling discovery biology with measures to account for pathophysiological diversity., (© 2024. Springer Nature Limited.)

Background: Cardiac sarcoidosis (CS) is a granulomatous disease that can manifest as conduction defects, ventricular arrhythmias, and heart failure. The diagnosis of CS is inherently difficult due to variable presentations; as such, endomyocardial biopsy is often required but lacks sensitivity due to patchy myocardial involvement. Moreover, the diagnostic criteria of CS and arrhythmogenic cardiomyopathy overlap, particularly in right-side dominant or biventricular presentations, which further complicates an already challenging differential diagnosis., Case Summary: A 53-year-old man with no prior chronic medical conditions presented with ventricular tachycardia (VT) and heart failure with reduced ejection fraction. He was found to have biventricular cardiomyopathy and late gadolinium enhancement on cardiac magnetic resonance imaging, resulting in an initial diagnosis of arrhythmogenic cardiomyopathy. Implantable cardioverter-defibrillator was placed, but he was readmitted for recurrent VT 2 months later. Despite an aggressive VT therapy (combination of antiarrhythmic drugs, epicardial and endocardial ablation, and stellate ganglion block), he continued with refractory VT and developed cardiogenic shock. Extra-corporeal membrane oxygenation was initiated as a bridge to heart transplantation. Pathology of the explanted heart revealed the underlying disease to be CS., Discussion: Cardiac sarcoidosis can mimic arrhythmogenic biventricular cardiomyopathy and may be difficult to distinguish by the proposed diagnostic criteria. High clinical suspicion and thorough investigation are necessary for an earlier diagnosis and initiation of treatment., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To examine the clinicopathologic features of patients with polymyalgia rheumatica (PMR) who had thoracic aorta repair surgery. Findings were compared with those of a cohort of patients with giant cell arteritis (GCA) requiring thoracic aorta repair., Methods: All patients evaluated at Mayo Clinic in Rochester, MN, with Current Procedural Terminology (CPT) codes for thoracic aorta repair surgery between 2000- 2021 were identified. All patients were screened for prior PMR diagnosis. Patients with PMR and no signs of GCA were categorized as clinically isolated PMR. The medical records of all patients were manually reviewed, and pathologists re-examined all the aortic tissues., Results: Of the 4621 patients with at least one CPT code for thoracic aorta repair surgery, 43 patients were diagnosed with clinically isolated PMR before the surgery. Detailed histopathological examination of the aortic tissues revealed active inflammation in 30/43 (70%) patients after a median (IQR) of 10.0 (4.7- 13.3) years from the PMR diagnosis. When compared with aortic tissue from patients with a prior diagnosis of GCA, the aorta of patients with PMR had more severe inflammation (Grade 3: 15/30 [50%] vs 5/34 [15%], p= 0.002). Patients with PMR and thoracic aorta repair may experience a 40% increased risk of mortality compared with the general population, but this did not reach statistical significance (standardized mortality ratio: 1.40; 95% CI: 0.91- 2.07)., Conclusions: Some patients with PMR have subclinical aortic inflammation that is detectable many years after initial diagnosis and may contribute to the development of aortic aneurysm., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Prognostic stratification of pulmonary carcinoids into "typical" and "atypical" categories requires examination of large tissue volume. However, there is a need for tools that provide similar prognostic information on small biopsy samples. Ki-67 and OTP immunohistochemistry have shown promising prognostic value in studies of resected pulmonary carcinoids, but prognostic value when using biopsy/cytology specimens is unclear. Ki-67 immunohistochemistry was performed on small biopsy/cytology specimens from pulmonary carcinoid tumors (n=139), and labeling index was scored via automated image analysis of at least 500 cells. OTP immunohistochemistry was performed on 70 cases with sufficient tissue and scored as positive or negative (<20% tumor nuclei staining). Higher Ki-67 index was associated with worse disease-specific progression-free survival (ds-PFS), with 3% and 4% thresholds having similarly strong associations with ds-PFS ( P <0.001, hazard ratio ≥11). Three-year ds-PFS was 98% for patients with Ki-67 <3% and 89% for patients with Ki-67≥3% ( P =0.0006). The optimal Ki-67 threshold for prediction of typical versus atypical carcinoid histology on subsequent resection was 3.21 (AUC 0.68). Negative OTP staining approached significance with atypical carcinoid histology ( P =0.06) but not with ds-PFS ( P =0.24, hazard ratio=3.45), although sample size was limited. We propose that Ki-67 immunohistochemistry may contribute to risk stratification for carcinoid tumor patients based on small biopsy samples. Identification of a 3% hot-spot Ki-67 threshold as optimal for prediction of ds-PFS is notable as a 3% Ki-67 threshold is currently used for gastrointestinal neuroendocrine tumor stratification, allowing consideration of a unified classification system across organ systems., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: ANCA-associated vasculitis (AAV) is currently categorized under the small vessel vasculitides. There is limited knowledge about large vessel involvement in AAV (L-AAV), mainly described in case reports and small series. L-AAV can involve temporal arteries (TA-AAV), aorta (A-AAV), and periaortic soft tissue (PA-AAV). We sought to characterize the features of patients with L-AAV., Methods: Patients older than 18 years at diagnosis of TA-AAV, A-AAV and PA-AAV seen at the Mayo Clinic, Rochester between 1 January 2000 and 31 December 2021 were identified through a proprietary medical text search algorithm. Patients were included if diagnosed with L-AAV, fulfilled 2022 ACR/EULAR classification criteria for GPA, MPA or EGPA, had positive ANCA test results, and had more than one outpatient or inpatient visit., Results: The study cohort consists of 36 patients with L-AAV. Of those, 23 had p-ANCA and/or MPO-ANCA, and 13 had c-ANCA and/or PR3-ANCA. Mean (s.d.) age at AAV diagnosis was 63.4 (12.79) years; 20 (56%) were male. Seventeen patients had TA-AAV, 10 had A-AAV and 9 had PA-AAV. Most patients (n = 25, 69%) were diagnosed with large vessel vasculitis and AAV within a 1-year timespan. Twenty-five (69%) patients had histopathological confirmation of AAV diagnosis in a location other than temporal artery, aorta or periaortic soft tissue. Glucocorticoids (36/36), rituximab (19/36) and methotrexate (18/36) were the most frequent treatments., Conclusion: This is the largest single-centre cohort of patients with L-AAV to date. AAV can involve large arteries, albeit infrequent. AAV-targeted therapy should be considered in patients with L-AAV., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Gangliocytic paragangliomas are rare neoplasms occurring almost exclusively in the ampullary region of the gastrointestinal tract. Although these tumors are not typically considered in the differential diagnosis of primary pulmonary neoplasia, 5 cases of primary pulmonary gangliocytic paragangliomas have been previously reported. Herein we report our experience with 3 additional examples, all referred to our Anatomic Pathology Consultation service. The patients (a 32-year-old man, a 69-year-old woman and a 55-year-old man) each presented with an endobronchial (2 cases) or upper lobe lung mass, ranging from 1.5 to 2.5 cm in maximum dimension. Biopsy and endobronchial debulking specimens demonstrated the classic triphasic morphology of gangliocytic paraganglioma, with epithelial, spindled and ganglion-like cells. By immunohistochemistry, the tumors were positive for keratin, synaptophysin and chromogranin A in the epithelial component, S100 protein and glial fibrillary acidic protein (GFAP) in the Schwannian spindled cells, and synaptophysin in ganglion cells. TTF1 expression was seen in the epithelial components of 2 cases. The Ki-67 labelling index was low (<2%). Primary pulmonary gangliocytic paragangliomas should be distinguished from carcinoid tumors, given the different natural histories and risk stratification approaches for these morphologically similar tumors. Awareness that gangliocytic paraganglioma may occur in the lung and appropriate immunohistochemical studies are key to correct diagnosis., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Papillary fibroelastomas are associated with an increased risk of embolic strokes. Excision of papillary fibroelastomas may be the primary indication for surgery (primary) or performed during other cardiac operations (secondary). The present study summarizes our experience with primary and secondary fibroelastoma surgery., Methods: We analyzed the medical records of patients who underwent surgical excision of papillary fibroelastoma between January 1998 and February 2020. Patient characteristics, indications for operation, tumor size and location, and operative and long-term outcomes were evaluated., Results: Among the 294 patients (median age: 66 years, 62% female), papillary fibroelastoma was the primary indication for surgery in 136 patients (46%), and 51% of patients had a history of stroke or transient ischemic attack. When papillary fibroelastoma was a secondary indication for surgery (158 patients, 54%), the lesion was identified preoperatively in 39%. Papillary fibroelastomas were located most commonly on the aortic valve and least commonly in the right side of the heart. For valvular papillary fibroelastoma resected from a normal valve, valve shave was sufficient in 96% (196/205). Operative mortality was low in both groups (primary, 0% vs secondary, 2.5%, P = .13), and early neurologic events occurred in 1.3%. Recurrence rate was 15.8% at 10 years. The estimated survival for patients with primary papillary fibroelastoma at 10 years was 78.4%, whereas for secondary papillary fibroelastoma removal it was 53.6% (log rank, P = .003)., Conclusions: Resection of papillary fibroelastomas can be performed safely, with preservation of the native valve, and with low rates of neurologic events. Operative and long-term outcomes after fibroelastoma resection are excellent., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) is most well-known for causing pulmonary injury, a significant proportion of patients experience hepatic dysfunction. The mechanism by which SARS-CoV2 causes liver injury is not fully understood. The goal of this study was to describe the hepatic pathology in a large cohort of deceased patients with COVID-19 as compared to a control group of deceased patients without COVID-19., Methods: Consented autopsy cases at two institutions were searched for documentation of COVID-19 as a contributing cause of death. A group of consecutive consented autopsy cases during the same period, negative for SARS-CoV-2 infection, was used as a control group. The autopsy report and electronic medical records were reviewed for relevant clinicopathologic information. H&E-stained liver sections from both groups were examined for pertinent histologic features. Select cases underwent immunohistochemical staining for CD 68 and ACE2 and droplet digital polymerase chain reaction (ddPCR) assay for evaluation of SARS-CoV2 RNA., Results: 48 COVID-19 positive patients (median age 73, M:F 3:1) and 40 COVID-19 negative control patients (median age 67.5, M:F 1.4:1) were included in the study. The COVID-19 positive group was significantly older and had a lower rate of alcoholism and malignancy, but there was no difference in other comorbidities. The COVID-19 positive group was more likely to have received steroids (75.6 % vs. 36.1 %, p < 0.001). Hepatic vascular changes were seen in a minority (10.6 %) of COVID-19 positive cases. When all patients were included, there were no significant histopathologic differences between groups, but when patients with chronic alcoholism were excluded, the COVID-19 positive group was significantly more likely to have steatosis (80.9 % vs. 50.0 %, p = 0.004) and lobular inflammation (45.7 % vs. 20.7 %, p = 0.03). Testing for viral RNA by ddPCR identified 2 of the 18 (11.1 %) COVID-19 positive cases to have SARS-CoV-2 RNA detected within the liver FFPE tissue., Conclusions: The most significant findings in the liver of COVID-19 positive patients were mild lobular inflammation and steatosis. The high rate of steroid therapy in this population may be a possible source of steatosis. Hepatic vascular alterations were only identified in a minority of patients and did not appear to play a predominant role in COVID-19 mediated hepatic injury. Low incidence of SARS-CoV-2 RNA positivity in liver tissue in our cohort suggests hepatic injury in the setting of COVID-19 may be secondary in nature., Competing Interests: Declaration of competing interest None of the authors have relevant conflict of interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Acute type A aortic dissection (ATAAD) remains a highly life-threatening condition. This study investigates factors associated with fatal ATAAD prior to surgical treatment., Methods: We reviewed autopsy reports of ATAAD decedents who died before surgical intervention and underwent postmortem examination at our clinic from 1994 to 2022., Results: Among 94 eligible cases, 50 (53.2%) decedents had DeBakey type I dissection, and 44 (46.8%) had DeBakey type II dissection. Most were males, 63 (67%), and 72 (77%) had a history of hypertension. The median age was 70.5 years, and the type II group was a decade older than the type I group (P < 0.001). Decedents in the type II group predominantly died during the first hour after symptoms onset 16 (52%), while in the type I group, fatalities occurred between 1 h and 1 day, 27 (66%). The most common site of the intimal tear was the midportion of the ascending aorta, 45 (48%). The median ascending aorta size was 5 cm for the entire cohort, 5.2 cm for type I and 4.6 cm for type II (P < 0.045)., Conclusions: In this autopsy study of fatal acute aortic dissection, the median aortic size was below the current guideline threshold for elective repair. Type II acute aortic dissections were found more frequently than expected and were characterized by older age, advanced aortic atherosclerosis, smaller aortic size, a shorter interval from symptom onset to death and a higher frequency of syncope compared to type I dissection., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Lambl excrescences (LEs) were initially described in the mid-1800s during autopsies of human hearts, and their significance and biology have been debated ever since. LEs are typically found on aortic and pulmonary valve (semilunar) cusps. There is debate concerning whether LEs are a significant cause of thromboembolic events, or whether they are harmless growths. However, there have not been many reports discussing LEs, and fewer still have examined the prevalence and characteristics of LEs in healthy human hearts. Those who have examined LE prevalence have reported a very high incidence of LEs (85-90%). Herein, we examine LE prevalence and characteristics (size, location, number) in 403 healthy human hearts across all age groups. We find that the prevalence of LEs in healthy hearts is far lower than previously reported., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Giant cell arteritis (GCA) is a systemic vasculitis affecting medium and large arteries in patients aged over 50 years. Involvement of temporal arteries (TA) can lead to complications such as blindness and stroke. While the diagnostic gold standard is temporal artery biopsy (TAB), comorbidities and age-related changes can make interpretation of such specimens difficult. This study aims to establish a baseline of TA changes in subjects without GCA to facilitate the interpretation of TAB., Methods and Results: Bilateral TA specimens were collected from 100 consecutive eligible postmortem examinations. Subjects were divided into four age groups and specimens semiquantitatively evaluated for eccentric intimal fibroplasia, disruption and calcification of the internal elastic lamina (IEL), medial attenuation and degree of lymphocytic inflammation of the peri-adventitia, adventitia, media and intima. The individual scores of intimal fibroplasia, IEL disruption and medial attenuation were added to yield a 'combined score (CS)'. Seventy-eight 78 decedents were included in the final analysis following exclusion of 22 individuals for either lack of clinical information or inability to collect TA tissue. A total of 128 temporal artery specimens (50 bilateral from individual decedents, 28 unilateral) were available for examination. Intimal proliferation, IEL loss, IEL calcification and CS increased with age in a statistically significant fashion. Comparison of the oldest age group with the others showed statistically significant differences, although this was not uniformly preserved in comparison between the three youngest groups., Conclusion: Senescent arterial changes and healed GCA exhibit histological similarity and such changes increase proportionally with age. The CS demonstrates significant association with age overall and represents a potential avenue for development to 'normalise' TA biopsies from older individuals., (© 2023 John Wiley & Sons Ltd.)

Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, and aortic aneurysm. The disease is often refractory to immunosuppressive therapy and progresses over decades as smoldering aortitis. How the granulomatous infiltrates in the vessel wall are maintained and how tissue-infiltrating T cells and macrophages are replenished are unknown. Single-cell and whole-tissue transcriptomic studies of immune cell populations in vasculitic arteries identified a CD4 + T cell population with stem cell-like features. CD4 + T cells supplying the tissue-infiltrating and tissue-damaging effector T cells survived in tertiary lymphoid structures around adventitial vasa vasora, expressed the transcription factor T cell factor 1 (TCF1), had high proliferative potential, and gave rise to two effector populations, Eomesodermin (EOMES) + cytotoxic T cells and B cell lymphoma 6 (BCL6) + T follicular helper-like cells. TCF1 hi CD4 + T cells expressing the interleukin 7 receptor (IL-7R) sustained vasculitis in serial transplantation experiments. Thus, TCF1 hi CD4 + T cells function as disease stem cells and promote chronicity and autonomy of autoimmune tissue inflammation. Remission-inducing therapies will require targeting stem-like CD4 + T cells instead of only effector T cells.

Objective: To identify the key coding genes underlying the biomarkers and pathways associated with giant cell arteritis (GCA), we performed an in situ spatial profiling of molecules involved in the temporal arteries of GCA patients and controls. Furthermore, we performed pharmacogenomic network analysis to identify potential treatment targets., Methods: Using human formalin-fixed paraffin-embedded temporal artery biopsy samples (GCA, n = 9; controls, n = 7), we performed a whole transcriptome analysis using the NanoString GeoMx Digital Spatial Profiler. In total, 59 regions of interest were selected in the intima, media, adventitia, and perivascular adipose tissue (PVAT). Differentially expressed genes (DEGs) (fold-change > 2 or < -2, p-adjusted < 0.01) were compared across each layer to build a spatial and pharmacogenomic network and to explore the pathophysiological mechanisms of GCA., Results: Most of the transcriptome (12,076 genes) was upregulated in GCA arteries, compared to control arteries. Among the screened genes, 282, 227, 40, and 5 DEGs were identified in the intima, media, adventitia, and PVAT, respectively. Genes involved in the immune process and vascular remodeling were upregulated within GCA temporal arteries but differed across the arterial layers. The immune-related functions and vascular remodeling were limited to the intima and media., Conclusion: This study is the first to perform an in situ spatial profiling characterization of the molecules involved in GCA. The pharmacogenomic network analysis identified potential target genes for approved and novel immunotherapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Parreau, Molina, Dumonteil, Goulabchand, Naves, Bois, Akil, Terro, Fauchais, Liozon, Jauberteau, Weyand and Ly.)

Fenestrations in semilunar valves of human hearts have been incidentally described during autopsies since the 1800s, and were thought to be a degenerative process of the valve cusps. Due to the nature of autopsy, prior literature has primarily examined these fenestrations in pathologic hearts, and has implicated them in leading to valve insufficiency, regurgitation, and cusp rupture. More recent studies have predicted an increase in fenestration prevalence in the rapidly aging United States and have warned of a potential increase in fenestration-related valvular pathology. Herein, we analyze fenestration prevalence in 403 healthy human hearts and report findings that differ from these prior reports, and emphasize that fenestrations may not necessarily portend significant valvular dysfunction., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest or funding to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Orthotopic heart transplantation for cardiac sarcoidosis (CS) is becoming increasingly common. Historically, there have been concerns regarding disease recurrence within the allograft. Although rarely reported in the literature, cases of recurrent CS tend to be observed in patients after dose reduction of immunosuppressive therapy and cessation of corticosteroids. Here, we present 2 cases of recurrent CS after orthotopic heart transplantation, confirmed on endomyocardial biopsy. Case 1 reports a 50-year-old man with a fulminant course of giant cell myocarditis who developed allograft recurrence with granulomas 5 years after transplantation despite maintenance corticosteroid therapy. Case 2 reports a 47-year-old man with CS who developed recurrence with the presence of giant cells 2 years after transplantation, with a benign clinical course. With these cases, we demonstrate the clinical overlap between CS and giant cell myocarditis and highlight the spectrum of the disease process. We also demonstrate that CS can recur despite corticosteroid maintenance therapy., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To investigate the clinicopathologic features of patients with giant cell arteritis (GCA) who had thoracic aorta aneurysm or dissection surgery., Methods: Patients who had thoracic aorta surgery between January 1, 2000, and December 31, 2021, at the Mayo Clinic, Rochester, Minnesota, were identified with current procedural terminology (CPT) codes. The identified patients were screened for a prior diagnosis of GCA with diagnostic codes and electronic text search. The available medical records of all the patients of interest were manually reviewed. Thoracic aorta tissues obtained during surgery were re-evaluated in detail by pathologists. The clinicopathologic features of these patients were analyzed. Overall observed survival was compared with lifetable rates from the United States population., Results: Of the 4621 patients with a CPT code for thoracic aorta surgery, 49 had a previous diagnosis of GCA. Histopathologic evaluation of the aortic tissue revealed active aortitis in most patients with GCA (40/49, 82%) after a median (IQR) of 6.0 (2.6-10.3) years from GCA diagnosis. All patients were considered in clinical remission at the time of aortic surgery. The overall mortality compared to age and sex-matched general population was significantly increased with a standardized mortality ratio of 1.55 (95% CI, 1.05-2.19)., Conclusion: Histopathologic evaluation of the thoracic aorta obtained during surgery revealed active aortitis in most patients with GCA despite being considered in clinical remission several years after GCA diagnosis. Chronic, smoldering aortic inflammation likely contributes to the development of aortic aneurysm and dissection in GCA., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kenneth J Warrington reports a relationship with Eli Lilly that includes: funding grants. Kenneth J Warrington reports a relationship with GlaxoSmithKline Inc. that includes: funding grants. Kenneth J Warrington reports a relationship with Kiniksa Pharmaceuticals Ltd. that includes: funding grants. Kenneth J Warrington reports a relationship with Sanofi that includes: consulting or advisory., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Carotid intraplaque hemorrhage (IPH) is considered a marker of plaque vulnerability. Cerebral microbleeds (CMBs) are recognized on magnetic resonance imaging (MRI) in patients with cerebrovascular disease. Any connection between carotid IPH and CMBs remains scantly investigated. This study aimed to determine whether the histologic evidence of carotid IPH is related to CMBs., Methods: We retrospectively enrolled 101 consecutive patients undergoing carotid endarterectomy with symptomatic (ischemic stroke, TIA, and amaurosis fugax) or asymptomatic ipsilateral carotid artery disease. The presence and the extent (%) of IPH were identified on carotid plaques stained with Movat Pentachrome. CMBs were localized on T2*-weighted gradient-recalled echo or susceptibility-weighted imaging sequence on brain MRI before surgery. The degree of carotid stenosis was measured by neck CTA., Results: IPH was identified in 57 (56.4%) patients, and CMBs were found in 24 (23.7%) patients. CMBs were more commonly observed in patients with carotid IPH compared to those without [19 (33.3%) vs 5 (11.4%); P=0.010]. The carotid IPH extent was significantly higher in patients with CMBs than in those without [9.0 % (2.8-27.1%) vs 0.9% (0.0-13.9%); P=0.004] and was associated with the number of CMBs (P=0.004). Logistic regression analysis demonstrated an independent association between carotid IPH extent and the presence of CMBs [OR 1.051 (95% CI 1.012-1.090); P=0.009]. Additionally, patients with CMBs had a lower degree of ipsilateral carotid stenosis compared to those without [40% (35-65%) vs 70% (50-80%); P=0.049]., Conclusions: CMBs may be potential markers of the ongoing process of carotid IPH, especially in those with nonobstructive plaques., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The cardiac conduction system is formed of histologically and electrophysiologically distinct specialized tissues uniquely located in the human heart. Understanding the anatomy and pathology of the cardiac conduction system is imperative to an interventional electrophysiologist to perform safe ablation and device therapy for the management of cardiac arrhythmias and heart failure. The current review summarizes the normal and developmental anatomy of the cardiac conduction system, its variation in the normal heart and congenital anomalies, and its pathology and discusses important clinical pearls for the proceduralist., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: In evaluating malignant pleural fluid cytology, metastatic adenocarcinomas and mesotheliomas are often differential diagnoses. GATA binding protein 3 (GATA3) has historically been used to confirm metastatic breast carcinomas; however, GATA3 has low specificity if mesothelioma is included in differential diagnoses. Trichorhinophalangeal syndrome type 1 (TRPS1) protein is expressed in all types of breast carcinomas, with reported high specificity and sensitivity. We investigated the performance of TRPS1 immunohistochemistry (IHC) and compared it to GATA3 in pleural fluids diagnosed with metastatic breast carcinoma and mesothelioma., Methods: Thirty-six consecutive ThinPrep pleural fluids and 4 pleural fine needle aspirations (FNAs) with diagnoses of metastatic breast carcinoma (21) and mesothelioma (19) were retrieved, and IHC with TRPS1 and GATA3 was performed on all. Immunoreactivity scores for TRPS1 were calculated by multiplying percentage of immunoreactive cells by staining intensity. Immunoreactivity scores were negative if 0 or 1, low positive if 2, intermediate positive if 3 or 4, or high positive if 6 or 9. Nuclear immunoreactivity of ≥10% with at least moderate intensity was judged GATA3 positive., Results: GATA3 showed immunoreactivity in all metastatic breast carcinomas and 84% of mesotheliomas. TRPS1 was immunoreactive in all breast carcinoma cases (18 with a score of 9 and 3 with a score of 6). TRPS1 showed low positivity in 5% of mesothelioma cases with all other cases being negative., Conclusion: When cytomorphologic differential diagnoses of mesothelioma exist, TRPS1 is a more specific marker than GATA3 for confirmation of metastatic breast carcinoma in pleural fluid cytology., (© 2023 Wiley Periodicals LLC.)

Lymphangioleiomyomatosis (LAM) is a rare disease with variable presentations. The neoplastic cells in LAM demonstrate a unique and diagnostically important "myomelanocytic" phenotype. Cytologic reports of LAM are infrequent and have not in the past emphasized the floating island pattern in which circumscribed aggregates of lesional cells are rimmed by appliques of flattened endothelium. This case illustrates the cytology of LAM and emphasizes that the floating island cytoarchitectural pattern more classically associated with entities such as hepatocellular carcinomas may be seen in cytological preparations of LAM at unanticipated body sites., (© 2023 Wiley Periodicals LLC.)

Loss of function of inhibitory immune checkpoints, unleashing pathogenic immune responses, is a potential risk factor for autoimmune disease. Here, we report that patients with the autoimmune vasculitis giant cell arteritis (GCA) have a defective CD155-CD96 immune checkpoint. Macrophages from patients with GCA retain the checkpoint ligand CD155 in the endoplasmic reticulum (ER) and fail to bring it to the cell surface. CD155 low antigen-presenting cells induce expansion of CD4 + CD96 + T cells, which become tissue invasive, accumulate in the blood vessel wall, and release the effector cytokine interleukin-9 (IL-9). In a humanized mouse model of GCA, recombinant human IL-9 causes vessel wall destruction, whereas anti-IL-9 antibodies efficiently suppress innate and adaptive immunity in the vasculitic lesions. Thus, defective surface translocation of CD155 creates antigen-presenting cells that deviate T cell differentiation toward Th9 lineage commitment and results in the expansion of vasculitogenic effector T cells., Competing Interests: Declaration of interests K.J.W. has received clinical trial support from Eli Lilly, GSK, and Kiniksa; he received consulting fees and honoraria from Chemocentryx., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

18 F-flurodeoxyglycose (FDG)/ 13 N-ammonia positron emission tomography/computed tomography (PET/CT) is frequently utilized to evaluate cardiac sarcoidosis (CS) but findings can reflect other forms of myocardial inflammation or altered myocardial metabolic activity. Herein, we present five cases where cardiac PET findings suggested CS, but right ventricular endomyocardial biopsy samples revealed ATTR-type cardiac amyloidosis., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Competing Interests: Disclosures of conflicts of interest: C.W.K. No relevant relationships. J.C.K.C. No relevant relationships. M.C.B. No relevant relationships.

Cardiac tumors are rare conditions, typically diagnosed on autopsy, but with the advancement of imaging techniques they are now encountered more frequently in clinical practice. Echocardiography is often the initial method of investigation for cardiac masses and provides a quick and valuable springboard for their characterization. While some cardiac masses can be readily identified by echocardiography alone, several require incorporation of multiple data points to reach diagnostic certainty. Herein, we will provide an overview of the main clinical, diagnostic, and therapeutic characteristics of cardiac masses within the framework of their location., Competing Interests: The authors report no conflict of interest., (© 2023 The Authors.)

A model's ability to express its own predictive uncertainty is an essential attribute for maintaining clinical user confidence as computational biomarkers are deployed into real-world medical settings. In the domain of cancer digital histopathology, we describe a clinically-oriented approach to uncertainty quantification for whole-slide images, estimating uncertainty using dropout and calculating thresholds on training data to establish cutoffs for low- and high-confidence predictions. We train models to identify lung adenocarcinoma vs. squamous cell carcinoma and show that high-confidence predictions outperform predictions without uncertainty, in both cross-validation and testing on two large external datasets spanning multiple institutions. Our testing strategy closely approximates real-world application, with predictions generated on unsupervised, unannotated slides using predetermined thresholds. Furthermore, we show that uncertainty thresholding remains reliable in the setting of domain shift, with accurate high-confidence predictions of adenocarcinoma vs. squamous cell carcinoma for out-of-distribution, non-lung cancer cohorts., (© 2022. The Author(s).)

Cardiac fibromas are rare primary tumors that can cause significant morbidity and mortality. There has not been a large clinical case review since 1994. This study provides an updated analysis of clinical impact, thereby enhancing understanding, increasing awareness, and revealing important factors in the diagnosis and management of cardiac fibromas. A retrospective case series was conducted at a tertiary care institution by reviewing radiology, surgical and pathology archives (1964 to 2020). Cases were included if cardiac fibroma was diagnosed through imaging or pathology. Demographics, symptomatology, electrophysiologic data, radiographic findings, pathology, interventions, and outcomes were examined. A total of 26 patients with cardiac fibromas were identified, including 12 women. The median age was 20.5 years (0 days to 72 years). Symptoms included palpitations (commonly due to ventricular tachycardia, 31%), syncope (15%), angina (15%), heart failure (12%), emboli (4%), and murmur (27%). One patient had Gorlin syndrome. A total of 22 patients were diagnosed through imaging, 15 of whom were biopsy-confirmed. A total of 9 patients were initially observed. A total of 2 eventually had surgery, 1 was lost to follow-up, 3 were asymptomatic, 1 had heart failure and atrial fibrillation, and 1 had atrial fibrillation and tachy-brady syndrome, requiring ablation and pacemaker placement. A total of 19 underwent resection. A total of 4 required complex operations, 1 required a second resection, and 1 operative death occurred. In conclusion, cardiac fibromas primarily affect the pediatric population; however, this study demonstrates a significant prevalence in adults. Ventricular tachycardia is common, and multimodality imaging is diagnostically sensitive. Resection is largely successful in symptomatic patients. Surveillance may be appropriate for asymptomatic patients., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The histologic criteria for myocarditis are a focal point of scientific debate in the wake of the SARS-CoV-2 pandemic. Variable methodologies have evolved in an evaluation already plagued by high intraobserver variability and low sensitivity. In this commentary, two topical manuscripts are reviewed in the context of this unfolding discussion., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size., Objectives: The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies., Data Sources: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory., Study Eligibility Criteria: Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection., Participants: Confirmed COVID-19 patients with post-mortem cardiovascular findings., Interventions: None., Methods: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs)., Results: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%)., Conclusions: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Uric acid (UA) concentration within carotid plaque and its association with cerebrovascular events have not been detected or quantified. Systemically, serum UA is a marker of inflammation and risk factor for atherosclerosis. However, its association with carotid plaque instability and stroke pathogenesis remains unclear. In patients undergoing carotid endarterectomy, we aimed to determine whether UA is present differentially in symptomatic versus asymptomatic carotid plaques and whether serum UA is associated with cerebrovascular symptoms (stroke, transient ischemic attack, or amaurosis fugax)., Methods: Carotid atherosclerotic plaques were collected during carotid endarterectomy. The presence of UA was assessed using Gomori methenamine silver staining as well as anti-UA immunohistochemical staining and its quantity measured using an enzymatic colorimetric assay. Clinical information was obtained through a retrospective review of data., Results: UA was more commonly detected in symptomatic (n=23) compared with asymptomatic (n=9) carotid plaques by Gomori methenamine silver (20 [86.9%] versus 2 [22.2%]; P =0.001) and anti-UA immunohistochemistry (16 [69.5%] versus 1 [11.1%]; P =0.004). UA concentration was higher in symptomatic rather than asymptomatic plaques (25.1 [9.5] versus 17.9 [3.8] µg/g; P =0.021). Before carotid endarterectomy, serum UA levels were higher in symptomatic (n=341) compared with asymptomatic (n=146) patients (5.9 [interquartile range, 4.6-6.9] mg/dL versus 5.2 [interquartile range, 4.6-6.2] mg/dL; P =0.009)., Conclusions: The current study supports a potential role of UA as a potential tissue participant and a systemic biomarker in the pathogenesis of carotid atherosclerosis. UA may provide a mechanistic explanation for plaque instability and subsequent ischemic cerebrovascular events.

Context.—: Studies of lungs in patients with COVID-19 have focused on early findings., Objective.—: To systematically study histopathologic and imaging features and presence of SARS-CoV-2 RNA in lung tissue from patients in later stages of COVID-19., Design.—: Autopsies, explants, surgical lung biopsies, transbronchial biopsies, cryobiopsies, and needle biopsies from patients with COVID-19 whose onset of symptoms/confirmed diagnosis was more than 28 days before the procedure were studied. Available images were reviewed. Reverse transcription droplet digital polymerase chain reaction for SARS-CoV-2 RNA was performed on lung tissue., Results.—: Of 44 specimens (43 patients; median age, 59.3 years; 26 [60.5%] male) features of acute lung injury (ALI) were seen in 39 (88.6%), predominantly organizing pneumonia and diffuse alveolar damage, up to 298 days after onset of COVID-19. Fibrotic changes were found in 33 specimens (75%), most commonly fibrotic diffuse alveolar damage (n = 22) and cicatricial organizing pneumonia (n = 12). Time between acquiring COVID-19 and specimen was shorter in patients with diffuse ALI (median, 61.5 days) compared with patients with focal (140 days) or no ALI (130 days) (P = .009). Sixteen (of 20; 80%) SARS-CoV-2 reverse transcription droplet digital polymerase chain reaction tests were positive, up to 174 days after COVID-19 onset. Time between COVID-19 onset and most recent computed tomography in patients with consolidation on imaging was shorter (median, 43.0 days) versus in patients without consolidation (87.5 days; P = .02). Reticulations were associated with longer time to computed tomography after COVID-19 onset (median, 82 versus 23.5 days; P = .006)., Conclusions.—: ALI and SARS-CoV-2 RNA can be detected in patients with COVID-19 for many months. ALI may evolve into fibrotic interstitial lung disease.

Background: Using computed tomography angiography to differentiate between components of carotid atherosclerotic lesions remains largely elusive. This study sought to validate a semi-automated software for computed tomography angiography plaque analysis using histologic comparisons., Materials and Methods: A retrospective review was performed of consecutive patients that underwent a carotid endarterectomy, with pre-procedural computed tomography angiography imaging of the cervical arterial vasculature available for review. Images were evaluated using a commercially-available software package, which produced segmented analyses of intraplaque components (e.g. intraplaque hemorrhage, lipid-rich necrotic core, and calcifications). On imaging, each component was assessed in terms of its (1) presence or absence, and (2) both volume and proportion of the total plaque volume (if present). On histological evaluation of carotid endarterectomy specimens, each component was evaluated as an estimated proportion of total plaque volume., Results: Of 80 included patients, 30 (37.5%) were female. The average age was 69.7 years (SD = 9.1). Based on imaging, intraplaque hemorrhage was the smallest contributor to plaque composition (1.2% of volumes on average). Statistically significant linear associations were noted between the proportion of intraplaque hemorrhage, lipid-rich necrotic core, and calcifications on histology and the volume of each component on imaging ( p values ranged from 0.0008 to 0.01). Area under curve were poor for intraplaque hemorrhage and lipid-rich necrotic core (0.59 and 0.61, respectively) and acceptable for calcifications (0.73)., Conclusion: Semi-automated analyses of computed tomography angiography have limited diagnostic accuracy in the detection of intraplaque hemorrhage and lipid-rich necrotic core in carotid artery plaques. However, volumetric imaging measurements of different components corresponded with histologic analysis.

Background: Papillary fibroelastoma (PFE) is the most common primary benign cardiac tumor. Because PFEs have the potential to embolize, they often are surgically excised. Prior studies have suggested that postoperative recurrence of PFE is rare or does not occur. We aimed to determine the rate at which PFEs recurred after surgical removal and to identify any risk factors associated with recurrence., Methods: We retrospectively identified all patients from a single center with pathologically proven PFE, treated from January 1995 through December 2018. Patients were included in the study if they had an echocardiographic examination at least 1 year after surgery. We compared echocardiographic images obtained intraoperatively (after excision) and at dismissal with those of the most recent examination to assess the possibility of PFE recurrence., Results: We included 98 patients in the study. The mean duration of follow-up was 5.4 (SD 3.7) years (range, 1 to 17); the median duration of follow-up was 4.3 years (interquartile range, 1.9 to 7.7). Twelve patients (12.2%) had echocardiographically supported PFE recurrence. Three patients had the recurrent lesion surgically reexcised, and pathologic analysis showed that two were recurrent PFEs and one was a Lambl excrescence. Initial clinical presentation of stroke or transient ischemic attack was more common for the recurrence group (for the first PFE) than for the nonrecurrence group (83% vs 26%; P < .001)., Conclusions: Contrary to findings from previous studies, PFEs do recur after surgical excision. These findings emphasize the importance of postoperative follow-up with transesophageal echocardiography for identifying recurrent masses., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The CTA "rim sign" has been proposed as an imaging marker of intraplaque hemorrhage in carotid plaques. This study sought to investigate such findings using histopathologic confirmation., Materials and Methods: Included patients had CTA neck imaging <1 year before carotid endarterectomy. On imaging, luminal stenosis and the presence of adventitial (<2-mm peripheral) and "bulky" (≥2-mm) calcifications, total plaque thickness, soft-tissue plaque thickness, calcification thickness, and the presence of ulcerations were assessed. The rim sign was defined as the presence of adventitial calcifications with internal soft-tissue plaque of ≥2 mm in maximum thickness. Carotid endarterectomy specimens were assessed for both the presence and the proportional makeup of lipid material, intraplaque hemorrhage, and calcification., Results: Sixty-seven patients were included. Twenty-three (34.3%) were women; the average age was 70.4 years. Thirty-eight (57.7%) plaques had a rim sign on imaging, with strong interobserver agreement (κ = 0.85). A lipid core was present in 64 (95.5%) plaques (average, 22.2% proportion of plaque composition); intraplaque hemorrhage was present in 52 (77.6%), making up, on average, 13.7% of the plaque composition. The rim sign was not associated with the presence of intraplaque hemorrhage ( P  = .11); however, it was associated with a greater proportion of intraplaque hemorrhage in a plaque ( P  = .049). The sensitivity and specificity of the rim sign for intraplaque hemorrhage were 61.5% and 60.0%, respectively., Conclusions: The rim sign is not associated with the presence of intraplaque hemorrhage on histology. However, it is associated with a higher proportion of hemorrhage within a plaque and therefore may be a biomarker of more severe intraplaque hemorrhage, if present., (© 2022 by American Journal of Neuroradiology.)

Background: Papillary fibroelastoma (PFE) are one of the most common primary cardiac neoplasms. They are most commonly found on cardiac valves especially on the left side of the heart and have been associated with an increased risk of embolization. To date, no large studies looked at the clinical significance of right-sided PFE (R-PFE). Therefore, we sought to better characterize patients with R-PFE and its clinical sequelae., Methods: We retrospectively identified patients with pathology-proven PFEs at a single center between January 1995 and December 2018 (n = 279). Patients with R-PFE were analyzed. Medical records and echocardiograms were reviewed for clinical and PFE characteristics., Results: Twenty-nine patients with R-PFE (mean age 70 ± 11 years; 62% women) were included in the analysis. PFEs were located on the right atrial (RA) wall in 31%, tricuspid valve in 34%, right ventricular (RV) wall in 7%, RV outflow tract in 4%, and pulmonary valve in 10% of patients. The remaining patients (14%) had multifocal PFEs. Around 38% of patients had cancer diagnosed before PFE diagnosis, and 34% had associated congenital heart disease. Seventeen (59%) patients had angina or dyspnea at the time of the presentation, and 3 (10%) had embolic symptoms. One patient with PFE located on the RA with associated patent foramen ovale had a stroke at time of presentation. Two patients, one with PFE on the RA wall and another patient with PFE at the tricuspid valve, had pulmonary embolism at the time of presentation. Median maximal length for PFE varied by location, ranging from a media of 8 mm to 16 mm. Of the 12 patients with follow up echocardiogram 1 year after PFE removal; 3/12 (25%) had documented PFE recurrence., Conclusion: R-PFE can be present in patients thromboembolic events when there is a right-to-left shunt. They can be a rare cause of pulmonary embolism, and at least in those that had follow-up echocardiograms, had a significant recurrence rate., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Carotid plaque vulnerability features beyond the degree of stenosis may play a key role in the pathogenesis and recurrence of ischemic cerebrovascular events. This study sought to compare intraplaque hemorrhage (IPH) as a marker of plaque vulnerability in symptomatic patients with mild (<50%), moderate (50%-69%), and severe (≥70%) carotid artery stenosis. We included patients who experienced ischemic cerebrovascular events with no other identifiable sources and underwent carotid endarterectomy for mild (n=32), moderate (n=47), and severe (n=58) carotid artery stenosis. The degree of stenosis and imaging hallmarks were assessed by computed tomography angiography or magnetic resonance angiography. Plaque specimens were stained with hematoxylin and eosin and Movat pentachrome staining. Carotid plaques of patients with mild stenosis had a higher extent of IPH (%) on tissue analysis compared with patients with moderate (mild, 15.7% [interquartile range, 7.8%-26.7%]; moderate, 3.9% [0.0%-9.2%]; P <0.001) and severe carotid artery stenosis (mild, 15.7% [interquartile range, 7.8%-26.7%]; severe, 2.5% [interquartile range, 0.0%-11.2%]; P <0.001). When considering the degree of carotid artery stenosis as a continuous variable, a lower lumen narrowing was associated with higher extent of IPH ( P <0.001; R, -0.329). Our major finding is the association of IPH with mild carotid artery stenosis based on histological analysis. The current study may suggest that IPH potentially plays a role in the mechanism of stroke in patients with nonobstructive carotid stenosis.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is one of the most common types of cardiac amyloidosis. Amyloid cardiomyopathy more commonly affects men, elderly, and 3% to 4% of the African-American population. ATTR-CM suspicion and diagnosis is challenging; however, awareness of the disease is increasing, and best practices to identify it are being proposed. The approach to suspected cases of ATTR-CM relies on the presence of heart failure, red flag signs and symptoms, and age >65 or >70 for men and women respectively. Little is known about cases when it presents in early ages. Case: We report a 62-year-old African American male with past medical history of hyperlipidemia, prostate cancer, hypertension, bilateral carpal tunnel surgery that had debuted with a cardiac arrhythmia at age 55 and was diagnosed with heart failure several years later. Restrictive cardiomyopathy was suspected, and genetic screening was sent for ATTRm which confirmed a pathogenic trasnthyretin gene mutation. Endomyocardial biopsy was performed which confirmed cardiac amyloid deposition. Discussion: ATTR-CM is a rare disease with an increasing prevalence. Cases with out of proportion signs and symptoms of heart failure with preserved ejection fractions should raise the suspicion of ATTR-CM despite age.