Abstract
Aims
Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement ...including elevated serum troponin levels and acute heart failure with reduced ejection fraction. The cardiac pathological changes in these patients with COVID-19 have yet to be well described.
Methods and results
In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists. The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry. Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement. Lymphocytic myocarditis was present in 3 (14%) of the cases. In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant. Increased interstitial macrophage infiltration was present in 18 (86%) of the cases. A mild pericarditis was present in four cases. Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases. There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified.
Conclusions
In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases. Other forms of myocardial injury are also present in these patients. The macrophage infiltration may reflect underlying diseases rather than COVID-19.
•The histologic diagnosis of myocarditis warrants revisiting in light of questions raised preceding and during the pandemic.•Interobserver variability remains high, with divergent practices in ...different regions of the world.•The diagnosis and implications of myocarditis are reviewed in conjunction with two relevant articles.
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.
The intersection of oncological and cardiovascular diseases is an increasingly recognized phenomenon. This recognition has led to the emergence of cardio-oncology as a true subspecialty. This field ...is not simply limited to primary cardiac tumors or complications of chemotherapeutic medications. Rather, it also encompasses metastatic cardiovascular complications and secondary cardiovascular effects of the underlying neoplasia. This review will broadly cover primary and metastatic cardiac neoplasms, as well as secondary cardiovascular effects of extracardiac neoplasia (e.g., amyloidosis, carcinoid valvulopathy, and chemotherapeutic cardiotoxicities).
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.
Pathology of Vaping-Associated Lung Injury Butt, Yasmeen M; Smith, Maxwell L; Tazelaar, Henry D ...
New England journal of medicine/The New England journal of medicine,
10/2019, Volume:
381, Issue:
18
Journal Article
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac ...complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection.
Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction.
Male sex was more common in the COVID-19 group (
=0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (
=0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (
=0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (
=0.69,
=1.00,
=0.46,
=0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations.
This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
The 2021 WHO Classification of Tumors of the Heart Maleszewski, Joseph J.; Basso, Cristina; Bois, Melanie C. ...
Journal of thoracic oncology,
April 2022, 2022-04-00, 20220401, Volume:
17, Issue:
4
Journal Article
XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque ...destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors.
Patients were stratified by symptoms, defined as presentation with an ipsilateral cerebral ischemic event. Carotid atherosclerotic plaques were obtained from 44 patients with symptomatic plaque and 44 patients without ischemic cerebral events. Protein expression of XO was evaluated by immunohistochemical staining and the percentage of cells expressing XO and CD68 (macrophage marker) compared between the groups. Biochemical and demographic cardiometabolic risk factors of study participants also were measured.
Carotid atherosclerotic plaques from symptomatic patients were associated with significantly higher XO expression versus asymptomatic plaque (median interquartile range: 1.24 2.09 versus 0.16 0.34; P<0.001) and with significantly higher circulating uric acid levels (mean±SD: 7.36±2.10 versus 5.37±1.79 mg/dL; P<0.001, respectively). In addition, XO expression in atherosclerotic carotid plaque was inversely associated with serum high-density lipoproteins cholesterol levels (P=0.010, r=−0.30) and directly with circulating uric acid levels (P<0.001, r=0.45). The average percentage of macrophages that expressed XO was significantly higher in symptomatic versus asymptomatic plaques (median interquartile range: 93.37% 25 versus 46.15% 21, respectively; P<0.001).
XO overexpression in macrophages is associated with increased serum uric acid and low high-density lipoproteins cholesterol levels and may potentially have a mechanistic role in carotid plaque destabilization. The current study supports a potential role for uric acid synthesis pathway as a target for management of carotid atherosclerosis in humans.
Coronary embolism is the underlying cause of 3% of acute coronary syndromes but is often not considered in the differential of acute coronary syndromes. It should be suspected in the case of high ...thrombus burden despite a relatively normal underlying vessel or recurrent coronary thrombus. Coronary embolism may be direct (from the aortic valve or left atrial appendage), paroxysmal (from the venous circulation through a patent foramen ovale), or iatrogenic (following cardiac intervention). Investigations include transesophageal echocardiography to assess the left atrial appendage and atrial septum and continuous electrocardiographic monitoring to assess for paroxysmal atrial fibrillation. The authors review the historic and contemporary published data about this important cause of acute coronary syndromes. The authors propose an investigation and management strategy for work-up and anticoagulation strategy for patients with suspected coronary embolism.
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