Pericardial Diseases: International Position Statement on New Concepts and Advances in Multimodality Cardiac Imaging.

Pericardial diseases have gained renewed clinical interest, leading to a renaissance in the field. There have been many recent advances in pericardial diseases in both multimodality cardiac imaging of diagnoses, such as recurrent, transient constrictive and effusive-constrictive pericarditis, and targeted therapeutics, especially anti-interleukin (IL)-1 agents that affect the inflammasome as part of autoinflammatory pathophysiology. There remains a large educational gap for clinicians, leading to variability in evaluation and management of these patients. The latest pericardial imaging (American Society of Echocardiography, European Association of Cardiovascular Imaging) and clinical guidelines (European Society of Cardiology) are >8-10 years of age and may not reflect current practice. Recent clinical trials involving anti-IL-1 agents in recurrent pericarditis, including anakinra (AIRTRIP), rilonacept (RHAPSODY), and goflikicept have demonstrated their efficacy. The present document represents an international position statement from world leaders in the pericardial field, focusing on novel concepts and emphasizing the role of multimodality cardiac imaging as well as new therapeutics in pericardial diseases.

Arrhythmogenic Left Ventricular Mass as the Initial Presentation of Cardiac Sarcoidosis.

Cardiac tumors of the left ventricle are rare, and cardiac magnetic resonance is the preferred imaging tool for evaluation given superior tissue characterization. We present a case of a patient with arrhythmia and left ventricular mass that was ultimately diagnosed with cardiac sarcoidosis, reminding us that tissue is the issue.

Consensus statement on the processing, interpretation and reporting of temporal artery biopsy for arteritis.

Giant cell arteritis (GCA) is the most common systemic vasculitis in adults in Europe and North America, typically involving the extra-cranial branches of the carotid arteries and the thoracic aorta. Despite advances in noninvasive imaging, temporal artery biopsy (TAB) remains the gold standard for establishing a GCA diagnosis. The processing of TAB depends largely on individual institutional protocol, and the interpretation and reporting practices vary among pathologists. To address this lack of uniformity, the Society for Cardiovascular Pathology formed a committee tasked with establishing consensus guidelines for the processing, interpretation, and reporting of TAB specimens, based on the existing literature. This consensus statement includes a discussion of the differential diagnoses including other forms of arteritis and noninflammatory changes of the temporal artery.

Thoracic Aortic Aneurysm and Dissection: Review and Recommendations for Evaluation.

ABSTRACT: Aortic dissection and rupture (collectively termed "sudden aortic death") are commonly encountered by forensic pathologists, with an estimated incidence at autopsy between 0.6% and 7.7%. Despite this, there is no standard of practice for the evaluation of sudden aortic death at autopsy.Recent studies have shown 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have an identifiable genetic syndrome, and 19% will have an affected first-degree relative. The past 2 decades have seen identification of new culprit genes and syndromes, which can have subtle or nonexistent external phenotypes. A high index of suspicion is warranted to identify possible hereditary TAAD (H-TAAD), allowing family members to obtain screening to avoid catastrophic vascular events. Forensic pathologists need broad knowledge of the spectrum of H-TAAD and awareness of the relative significance of hypertension, pregnancy, substance use, and microscopic changes of aortic architecture.This article reviews the common subtypes of H-TAAD, including Marfan syndrome, vascular Ehlers-Danlos, Loeys-Dietz, and familial thoracic aortic aneurysm and dissection. Recommendations for the evaluation of sudden aortic death at autopsy are presented, including (1) performance of a complete autopsy, (2) documentation of aortic circumference and valve morphology, (3) notifying family of the need for screening, and (4) preservation of a sample for potential genetic testing.

Histologic and Immunohistochemical Features of Antemortem Thrombus Compared to Postmortem Clot: Updating the Definition of Lines of Zahn.

CONTEXT.­: Distinguishing true antemortem thrombus (AMT) from artifactual postmortem clot (PMC) can occasionally be challenging at autopsy. Lines of Zahn are cited as pathognomonic of AMT, but review of literature reveals heterogeneous definitions of the term. Neutrophil karyorrhexis and CD61 immunohistochemistry can also be used to define AMT, but there has been no systematic study determining the specificity of these features. OBJECTIVE.­: To identify features that distinguish AMT from PMC, and to clarify the definition of lines of Zahn. DESIGN.­: PMC from the heart was collected in 50 hospital autopsies. Fifty arterial and 50 venous surgical thrombectomy specimens were reviewed for comparison. The microscopic features with hematoxylin-eosin staining, phosphotungstic acid-hematoxylin (PTAH) staining, and CD61 immunohistochemistry were documented. RESULTS.­: Thin curvilinear strands of fibrin and clumps of fibrin were frequently observed in both AMT and PMC. Thick bands of nested platelets wrapped in fibrin were nearly exclusive to AMT. Neutrophil karyorrhexis was readily apparent on low power in AMT but was seen in 40 of 50 PMCs (80%) only sparsely on high-power examination. Bone marrow elements were identified in 38 of 50 PMCs (76%). CD61 staining showed a geographic pattern in AMT and a speckled pattern in PMC. PTAH staining confirmed features seen with hematoxylin-eosin. CONCLUSIONS.­: Thin curvilinear strands of fibrin are found in both AMT and PMC and can be misinterpreted as lines of Zahn. We define lines of Zahn as thick bands formed by nested platelets wrapped in fibrin. Diffuse neutrophil karyorrhexis is common in AMT; in contrast, bone marrow elements are often seen in PMC.

Sudden cardiac death in the young: A consensus statement on recommended practices for cardiac examination by pathologists from the Society for Cardiovascular Pathology.

Sudden cardiac death is, by definition, an unexpected, untimely death caused by a cardiac condition in a person with known or unknown heart disease. This major international public health problem accounts for approximately 15-20% of all deaths. Typically more common in older adults with acquired heart disease, SCD also can occur in the young where the cause is more likely to be a genetically transmitted process. As these inherited disease processes can affect multiple family members, it is critical that these deaths are appropriately and thoroughly investigated. Across the United States, SCD cases in those less than 40 years of age will often fall under medical examiner/coroner jurisdiction resulting in scene investigation, review of available medical records and a complete autopsy including toxicological and histological studies. To date, there have not been consistent or uniform guidelines for cardiac examination in these cases. In addition, many medical examiner/coroner offices are understaffed and/or underfunded, both of which may hamper specialized examinations or studies (e.g., molecular testing). Use of such guidelines by pathologists in cases of SCD in decedents aged 1-39 years of age could result in life-saving medical intervention for other family members. These recommendations also may provide support for underfunded offices to argue for the significance of this specialized testing. As cardiac examinations in the setting of SCD in the young fall under ME/C jurisdiction, this consensus paper has been developed with members of the Society of Cardiovascular Pathology working with cardiovascular pathology-trained, practicing forensic pathologists.

Differences in Aortic Histopathology in Patients Undergoing Valve Reimplantation Surgery for Various Clinical Syndromes.

OBJECTIVES: The study aims to investigate aortic histopathologic differences among patients undergoing aortic valve reimplantation, suggest different mechanisms of aortic root aneurysm pathogenesis, and identify factors associated with long-term success of reimplantation. METHODS: From 2006 to 2017, 568 adults who underwent reimplantation for repair of aortic root aneurysm, including patients with tricuspid aortic valves with no connective tissue disease (TAV/NoCTD, n = 314/568; 55.3%), bicuspid aortic valves (BAVs, n = 86/568; 15.1%), or connective tissue disease (CTD, n = 177/568; 31.2%), were compiled into three comparison groups. Patients with both BAV and CTD (n = 9/568; 1.6%) were omitted to increase study power. Patient records were analyzed retrospectively, focusing on pathology reports, which were available for 98.42% of patients, and were classified based on their descriptions of aortic tissue samples, primarily from the noncoronary sinus. Mean follow-up time available for patients was 2.97 years. RESULTS: Aortitis, medial fibrosis, and smooth muscle loss were more common histopathologic findings in patients with TAV/NoCTD than in patients with BAV and CTD (p < 0.05). Cystic medial degeneration was most often found in patients with CTD, then TAV/NoCTD, and least in BAV (p < 0.01). Increases in mucopolysaccharides were found more often in the BAV group than in the TAV/NoCTD and CTD groups (p < 0.01). There were no differences in the frequency of elastic laminae fragmentation/loss across these three groups. Among all patients, 1.97% (n = 11/559) had an unplanned reintervention on the aortic valve after reimplantation, but no significant demographic or histopathologic differences were identified. CONCLUSION: Despite some common histopathologic features among patients undergoing aortic valve reimplantation, there were enough distinguishing features among aortic tissue samples of TAV/NoCTD, BAV, and CTD patients to suggest that these groups develop root aneurysms by different mechanisms. No histopathologic features were able to predict the need for late reintervention on the aortic valve.

Mitral annular calcification and valvular dysfunction: multimodality imaging evaluation, grading, and management.

Mitral annular calcification (MAC) refers to calcium deposition in the fibrous skeleton of the mitral valve. It has many cardiovascular associations, including mitral valve dysfunction, elevated cardiovascular risk, arrhythmias, and endocarditis. Echocardiography conventionally is the first-line imaging modality for anatomic assessment, and evaluation of mitral valve function. Cardiac computed tomography (CT) has demonstrated importance as an imaging modality for the evaluation and planning of related procedures. It also holds promise in quantitative grading of MAC. Currently, there is no universally accepted definition or classification system of MAC severity. We review the multimodality imaging evaluation of MAC and associated valvular dysfunction and propose a novel classification system based on qualitative and quantitative measurements derived from echocardiography and cardiac CT.

Invasive Aortic Valve Endocarditis: Clinical and Tissue Findings From a Prospective Investigation.

BACKGROUND: Advanced aortic valve infective endocarditis (IE) with progression and destruction beyond the valve cusps-invasive IE-is incompletely characterized. This study aimed to characterize further the invasive disease extent, location, and stage and correlate macroscopic operative findings with microscopic disease patterns and progression. METHODS: A total of 43 patients with invasive aortic valve IE were prospectively enrolled from August 2017 to July 2018. Of these patients, 23 (53%) had prosthetic valve IE, 2 (5%) had allograft IE, and 18 (42%) had native aortic valve IE. Surgical findings and intraoperative photography were analyzed for invasion location, extent, and stage. Surgical samples were formalin fixed and analyzed histologically. The time course of disease and management were evaluated. RESULTS: Pathogens included Staphylococcus aureus in 17 patients (40%). Invasion predominantly affected the non-left coronary commissure (76%) and was circumferential in 15 patients (35%) (14 had prosthetic valves). Extraaortic cellulitis was present in 29 patients (67%), abscess in 13 (30%), abscess cavity in 29 (67%), and pseudoaneurysm in 8 (19%); 7 (16%) had fistulas. Histopathologic examination revealed acute inflammation, abscess formation, and lysis of connective tissue but not of myocardium or elastic tissue. Median time from onset of symptoms to antibiotics was 5 days, invasion confirmation 15 days, and surgery 37 days. Patients with S aureus had a 21-day shorter time course than patients non-S aureus. New or worsening heart block developed in 8 patients. CONCLUSIONS: Advanced invasive aortic valve IE demonstrates consistent gross patterns and stages correlating with histopathologic findings. Invasion results from a confluence of factors, including pathogen, time, and host immune response, and primarily affects the fibrous skeleton of the heart and expands to low-pressure regions.

A Clinico-Pathologic Approach to the Differential Diagnosis of Pericardial Tumors.

PURPOSE OF REVIEW: Tumors of the pericardium are rare, but a wide variety of congenital, infectious, inflammatory, and neoplastic processes have been reported. Pericardial tumors can be categorized as non-neoplastic or neoplastic. Neoplastic lesions can be further divided into benign or malignant, with malignancies being either primary or secondary (metastatic). Clinical, radiographic, and pathologic features of the most common entities are discussed. RECENT FINDINGS: Metastatic neoplasms involving the heart and pericardium are far more common than primary pericardial neoplasms. Of primary pericardial malignancies, mesothelioma is the most common; notably, cytology of effusion fluid is relatively insensitive to the diagnosis. The prognosis for most malignancies of the pericardium, primary or secondary, is poor. Increasingly, clinically recognized diseases that involve the pericardium include Erdheim-Chester and IgG4-related disease. This article provides a comprehensive review of the most recent literature to develop a structured framework to the differential diagnosis of pericardial tumors.

Case report of isolated cardiac sarcoidosis presenting as hypertrophic obstructive cardiomyopathy-a clinical picture printed on lenticular paper.

BACKGROUND: Cardiac sarcoidosis (CS) is an inflammatory granulomatous process of the myocardium that can be asymptomatic or have several different clinical phenotypes. One of its rarely described presentations consists of hypertrophy of the septal myocardium, similar to hypertrophic cardiomyopathy (HCM). Isolated cardiac sarcoidosis that haemodynamically mimics hypertrophic obstructive cardiomyopathy (HOCM) has been rarely described in the literature. CASE SUMMARY: A 64-year-old Caucasian female previously diagnosed with non-critical aortic stenosis presented with pre-syncope, and echocardiography showed significant obstruction based on left ventricular outflow tract gradients, confirmed by cardiac magnetic resonance (CMR), concerning for a phenocopy of HCM. Septal myectomy was performed and pathology specimen revealed non-caseating granulomata consistent with cardiac sarcoidosis. She was started on oral corticosteroids and initial cardiac fluorodeoxyglucose positron emission tomography (FDG-PET) done after 1 month of treatment was negative. Repeat FDG-PET 15 months later, in the setting of haemodynamic decompensation, demonstrated diffuse FDG uptake in the myocardium without extra-cardiac involvement. DISCUSSION: Our case brings together two entities: isolated cardiac sarcoidosis and its presentation mimicking HOCM, which has been very rarely described in the literature. And it also shows the scenario of surgical pathology diagnosis of sarcoidosis that was not suspected by initial CMR or FDG-PET, despite adequate preparation, only appearing on repeat FDG-PET done 15 months later. Isolated cardiac sarcoidosis should remain a differential diagnosis for any non-ischaemic cardiomyopathy without a clear cause, despite imaging evidence of HCM.

Development of sacral/buttock retiform purpura as an ominous presenting sign of COVID-19 and clinical and histopathologic evolution during severe disease course.

Retiform purpura has been described as a relatively frequent cutaneous finding in patients with coronavirus disease 2019 (COVID-19). The etiology is hypothesized to be related to thrombotic vasculopathy based on lesional biopsy specimen findings, but the pathogenesis of the vasculopathy is not completely understood. Here, we present a case of a retiform purpuric patch on the sacrum/buttocks in a hospitalized patient prior to subsequent diagnosis of COVID-19 and an eventual fatal disease course. Two lesional biopsy specimens at different time points in the disease course revealed thrombotic vasculopathy, despite therapeutic anticoagulation. Detailed histopathologic evaluation using immunohistochemical markers suggest the etiology of the vasculopathy involves both persistent complement activation and platelet aggregation, which possibly promote ongoing thrombus formation. This case highlights that sacral/buttock retiform purpuric patches may be a presenting sign of infection with SARS-CoV-2 virus and may represent an ominous sign supporting a future severe disease course. In addition, biopsy specimen findings at separate time points demonstrate that cutaneous vasculopathy may persist despite adequate systemic anticoagulation, possibly due to the combination of persistent complement and platelet activation. Finally, occlusive thrombi in sacral/buttock retiform purpuric patches may contribute to future ulceration and significant cutaneous morbidity in patients who survive COVID-19.

Pulmonary Pathology of COVID-19 Following 8 Weeks to 4 Months of Severe Disease: A Report of Three Cases, Including One With Bilateral Lung Transplantation.

OBJECTIVES: Current knowledge of the pulmonary pathology of coronavirus disease 2019 (COVID-19) is based largely on postmortem studies. In most, the interval between disease onset and death is relatively short (<1 month). Information regarding lung pathology in patients who survive for longer periods is scant. We describe the pathology in three patients with severe COVID-19 who underwent antemortem examination of lung tissue at least 8 weeks after initial diagnosis. METHODS: We conducted a retrospective case series. RESULTS: The first patient developed acute respiratory failure and was started on extracorporeal membrane oxygenation (ECMO) on day 21, with subsequent hemothorax. Debridement (day 38) showed extensive lung infarction with diffuse alveolar damage and Candida overgrowth. The second patient developed acute respiratory failure requiring mechanical ventilation that did not improve despite ECMO. Surgical lung biopsy on day 74 showed diffuse interstitial fibrosis with focal microscopic honeycomb change. The third patient also required ECMO and underwent bilateral lung transplantation on day 126. The explanted lungs showed diffuse interstitial fibrosis with focal microscopic honeycomb change. CONCLUSIONS: This series provides histologic confirmation that complications of COVID-19 after 8 weeks to 4 months of severe disease include lung infarction and diffuse interstitial fibrosis.

Proteomics identifies a convergent innate response to infective endocarditis and extensive proteolysis in vegetation components.

Infective endocarditis is a life-threatening infection of heart valves and adjacent structures characterized by vegetations on valves and other endocardial surfaces, with tissue destruction and risk of embolization. We used high-resolution mass spectrometry to define the proteome of staphylococcal and non-staphylococcal vegetations and Terminal Amine Isotopic Labeling of Substrates (TAILS) to define their proteolytic landscapes. These approaches identified over 2000 human proteins in staphylococcal and non-staphylococcal vegetations. Individual vegetation proteomes demonstrated comparable profiles of quantitatively major constituents that overlapped with serum, platelet, and neutrophil proteomes. Staphylococcal vegetation proteomes resembled one another more than the proteomes of non-staphylococcal vegetations. TAILS demonstrated extensive proteolysis within vegetations, with numerous previously undescribed cleavages. Several proteases and pathogen-specific proteins, including virulence factors, were identified in most vegetations. Proteolytic peptides in fibronectin and complement C3 were identified as potential infective endocarditis biomarkers. Overlap of staphylococcal and non-staphylococcal vegetation proteomes suggests a convergent thrombotic and immune response to endocardial infection by diverse pathogens. However, the differences between staphylococcal and non-staphylococcal vegetations and internal variance within the non-staphylococcal group indicate that additional pathogen- or patient-specific effects exist. Pervasive proteolysis of vegetation components may arise from vegetation-intrinsic proteases and destabilize vegetations, contributing to embolism.

Imaging-Guided Therapies for Pericardial Diseases.

Frequently, multimodality imaging is indispensable in the care of patients with pericardial disease. With cardiac magnetic resonance imaging, pericardial inflammation can be characterized as acute, subacute, or chronic. This spectrum of inflammation is variably associated with reduced compliance of the pericardium, which may result in constrictive pathophysiology, typically well-defined with echocardiography. This interplay between inflammation and hemodynamics is often optimally characterized with multimodality imaging and has redefined the approach of pericardiologists to diagnose, prognosticate, and tailor individual therapies.