Calcific Aortic Stenosis - Inflammatory Disease.

In developed countries, calcific aortic stenosis (CAS) has become the most common acquired valvular disease and cause for valve replacement. The prevalence of the disease increases with age, reaching over 5 % in adults over 75 years of age. The cases of CAS are classified as either of a previously normal (tricuspid) aortic valve (senile, syn. age - related, "sclerotic" type), or based on a congenitally malformed, usually bicuspid aortic valve. This paper is a brief summary of our 5 previous publications from the years 2007 - 2021, devoted to histopathology of CAS, namely to vascularization, inflammatory infiltrate and metaplastic ossification of the valve, and also to topography of these lesions in individual valve cusps. We conclude that calcification of the aortic valve is not a passive degenerative lesion, but an active multifactorial inflammatory process driven by cells native to the aortic valve. Pathogenesis of CAS is similar to that of atherosclerosis.

Mitral valve rheumatoid nodule complicated by infective endocarditis.

We report a case of a 73-year-old male with rheumatoid arthritis presenting with acute abdominal and back pain and rapidly developing multiorgan failure. A positive blood culture (Staphylococcus aureus, Candida species) followed by transoesophageal sonography established a diagnosis of mitral valve infective endocarditis. At the autopsy, the heart examination revealed fibrinous pericarditis and multiple small vegetations on the mitral valve. The mitral valve itself showed no significant damage. Surprisingly, the histological examination of the mitral valve showed granulomatous inflammation with central fibrinoid necrosis and peripheral palisade of histiocytes, with occasional giant cells and lymphocytic inflammatory infiltrate - findings consistent with a rheumatoid nodule. Infective vegetations were overlying the nodule. Due to its relative frequency, a possibility of cardiac involvement by rheumatoid arthritis and its potential infective complications should be considered in patients with appropriate history and clinical symptoms.

Cardiac myxoma with atypical cell population mimicking malignancy - a diagnostic pitfall.

Herein, a case of a 45-year-old woman is reported with left atrial myxoma showing unique histological findings mimicking malignancy. For 3 months before surgery, the patient suffered from a long-standing fever of unknown etiology, malaise and weight loss; she had no history of malignancy. The CT scan revealed a tumorous mass in the left atrium. Grossly, the tumor had a smooth rounded surface with areas of haemorrhage on the cut surface. Microscopic examination revealed two distinct regions. One showed classical myxoma histology, the other atypical and highly cellular population with sarcoma-like or melanoma-like features mixed with inflammatory cells and posthemorrhagic changes. Immunohistochemically, the atypical cells expressed calretinin and CD31, analogous to the neighbouring bland myxoma cells. Negative markers included SOX10, S100, Melan A, HMB45, CD34, desmin, ERG, CK, LCA, CD68 and MDM2; SMARCB1/INI1 was retained. The proliferation index Ki67 was low, in about 1 % of atypical cells. The results suggest exaggerated reactive and degenerative changes of the myxoma cells rather than true malignant transformation. Similar case reports of cardiac myxomas and diagnostic challenges are discussed.

Medial degeneration and atherosclerosis show discrete variance around the circumference of ascending aorta aneurysms.

Medial degeneration is the most common histological finding in ascending aortic aneurysms with lesser but significant involvement by atherosclerosis. The overall extent and severity can be potentially underrated because of their uneven distribution and macroscopic inconspicuousness of medial degeneration. This study aims to compare the distribution of degenerative and atherosclerotic lesions around ascending aorta circumference, also considering aortic valve cuspidity. We evaluated 88 cases of resected ascending aortae, 25 with a tricuspid aortic valve and 63 with a malformed aortic valve, oriented by a cardiac surgeon and sent for pathological examination. We applied the consensus documents from 2015 and 2016 for microscopic evaluation of aortic specimens. The medial degeneration and atherosclerosis were graded semi-quantitatively for each aortic quadrant: convexity, anterior wall, concavity, and posterior wall. Nearly all quadrants showed at least mild medial degeneration; more severe findings of medial degeneration and atherosclerosis were in the aneurysms associated with the tricuspid valve. In the aneurysms with the tricuspid aortic valve, there was more frequent and more severe atherosclerosis at the concavity than at the anterior wall (p = .046); the frequency and severity of medial degeneration did not differ significantly. The aneurysms with a malformed aortic valve showed more severe medial degeneration at the concavity compared to the convexity (p = .011); atherosclerosis was less common and did not show any significant differences. More than half of the samples also revealed at least a one-grade (mostly one-grade) difference among the quadrants in individual cases for both atherosclerosis and medial degeneration. Extreme differences were rare except for atherosclerosis in the tricuspid group. The results revealed only slight overall differences around the aortic circumference, with concavity being the most susceptible. Still, thanks to occurring inter- and intraindividual variability, the examination of all quadrants seems meaningful not to miss the most severe changes and to underscore the findings.

Is obesity a risk factor for coronary atherosclerosis?

A group of 279 adult autopsy patients (66 obese with BMI 30, versus 213 nonobese with BMI < 30) was retrospectively studied for the relation between body weight and coronary artery atherosclerosis. In the obese group, there was slightly higher grade of coronary narrowing than in the nonobese (2.31/2.5 versus 2.12/2). With increasing BMI in the obese, there was a statistically significant trend for milder coronary atherosclerosis, with least involvement in the extremely obese (BMI > 50). It seems that increased body weight by itself has little impact on coronary atherosclerosis, and extreme obesity may even by protective from it.

Calcific aortic valve stenosis - comparison of inflammatory lesions in the left, right, and non-coronary cusp.

BACKGROUND: Calcific aortic valve stenosis (CAVS) is the most frequent acquired heart valve disease in the developed world and the most common cause of heart valve replacement, particularly in older adults. It is considered a form of atherosclerosis and, like the latter, of inflammatory pathogenesis. METHODS: The incidence and severity of features of chronic inflammation (vascularization, cellular infiltration, bone metaplasia, calcification) in surgically resected semilunar cusps of a tricuspid aortic valve in 100 patients with CAVS were assessed. A novel method of placing metal clips during the operation by the surgeon to distinguish individual cusps was implemented, allowing the pathologist to associate lesions to particular cusps. The findings were evaluated statistically. RESULTS: The median age of the cohort was 73 years. There was a male predominance of 3.5:1. Almost all the patients had a medical history of risk factors - hypertension (92x), diabetes (51x), and dyslipidaemia (85x). Statistical evaluation of the pathological findings showed that the left cusp was least affected by calcification, vascularization, and chronic inflammation, compared to both the right and non-coronary cusps. On the other hand, the left cusp was the most common site of bone metaplasia. The reason for these differences is unknown. We speculate about mechanobiological effects of abnormal hemodynamics. CONCLUSIONS: Chronic inflammation plays a significant role in pathogenesis of CAVS. Distinguishing the resected aortic valve cusps by placing metal clips is a useful method to study potential differences (topography) in the pathology of individual cusps.

Ascending aorta dissection in a new classification system: Clinicopathological features of 62 cases.

Herein we present a single institution 5-year experience with ascending aorta dissection biopsies depicting the clinicopathological features of 62 cases. To detect microscopic abnormalities in the aortic wall beside the dissection itself, we applied a new histopathological classification scheme from the consensus documents issued by The Society for Cardiovascular Pathology and The Association for the European Cardiovascular Pathology in 2015 and 2016. The most common finding was medial degeneration (MD) - 61 cases (98.4%); atherosclerosis (AS) was found in 19 aortae (30.6%), and chronic aortitis- giant cell pattern described in one aorta (1.6%). The medial degeneration constituents included mucoid matrix accumulation, smooth muscle cells and elastic fibers abnormalities, and medial fibrosis. The consensus document application led to increased MD reporting compared to older studies and to our previous experience, probably due to assessing more subtle and focal changes such as intralamellar fibrosis, intralamellar mucoid matrix accumulation, and loss of smooth muscle cell nuclei- these changes being also the most common MD abnormalities we are reporting. We have compared the results in patients with bicuspid (n = 7; 11.3%) versus tricuspid (n = 55; 88.7%) aortic valve, suggesting no significant differences except for translamellar fibrosis, which appeared to be more severe in the bicuspid valve group (p = 0.0397). The results might imply similar histopathological findings regardless of the aortic valve cuspidity in aortic dissection. These findings are in contrast to ascending aorta dilation (aneurysm), where more severe medial degeneration changes have been described in patients with the tricuspid aortic valve.

Hydrophilic polymer embolization as an iatrogenic complication of endovascular interventions - a new entity.

Iatrogenic hydrophilic polymer embolization (HPE) is an underrecognised complication of endovascular procedures. In certain instances, HPE and related complications may lead to patiens death. Incidence of this phenomenon is not known. We evaluated retrospectively all autopsies of patients with a history of endovascular intervention performed by one pathology resident during a period of 8 months. There were 10 cases, which were examined histochemically and in polarized light.  We detected HPE in 2 of the 10 cases. In both cases the involved organ were lungs. Hydrophilic polymer embolization is a potential and easy-to-miss complication of endovascular procedures. It must be considered during histological examination of autoptic material.

Pathologia mutans.

The authors present results of our center retrospective study comparing autopsy findings from years 1929 (n=275) and 1989 (n=974). The male to female ratio was very similar in both cohorts (1.3:1 in 1929 and 1.4:1 in 1989). The age range in 1929 was 0-88 years with median of 50 years, whereas in 1989, the age range was 0-98 year and median was 65 years. Among lethal diseases in 1929 were namely infections and infectious complications - 61 % of all patients (out of these, 18 % were tuberculosis cases), neoplasms (12 %) and cardiovascular disorders (6.5 %). In 1989, malignant neoplasms were most frequent (31 %), followed by cardiovascular disorders (21 %) and infections (4.6 % - out of these, tuberculosis represented only 0.6 %). Our study is unique by comparing two well documented autopsy cohorts in a single center from two years being 60 years apart. The study clearly demonstrates dramatic changes in healthcare achieved during the 20th century.

Pathology of radiation induced heart disease.

The aim of this paper is dual - to review the relevant literature on pathology of radiation induced heart disease (RIHD), and to present an illustrative case of our own. Therapeutic ionizing radiation, such as that used in the treatment of Hodgkin´s lymphoma and cancers of left breast, lungs, esophagus, and thymus, can cause cardiac damage that may take several years to manifest. The spectrum of RIHD is broad and includes [1] pericarditis and pericardial effusion; [2] endocardial fibrosis and valvular dysfunction; [3] nonischemic myocardial fibrosis; [4] obstructive coronary artery disease with resultant myocardial ischemia; [5] damage to the great vessels; and [6] conduction system dysfunction. Pericardial disease, however, is the most common manifestation of mediastinal irradiation. A case is described of a typical RIHD in a 52-year-old female who died from heart failure with a history of mediastinal neuroblastoma operated and irradiated at the age of 9 years. Her autopsy heart lesions comprised chronic and acute pericarditis with constrictive features, myocardial fibrosis with features of restrictive cardiomyopathy and fibrosis with calcification of the left heart valves. As a unique lesion, there were small calcifications in the mural endocardium and in the large arterial intima. This finding seems to be diagnostic for RIHD.

Moyamoya disease associated with fibromuscular dysplasia of intrapulmonary bronchial arteries-a case report.

A case is reported of a 40-year-old woman clinically diagnosed as moyamoya disease with associated fibromuscular dysplasia of intrapulmonary bronchial arteries incidentally revealed during autoptic examination. Moyamoya disease represents an idiopathic noninflammatory and nonatherosclerotic arterio-occlusive process of intracranial arteries. Prolonged brain ischemia leads to formation of tiny and fragile collaterals. Clinically, patients with moyamoya angiopathy commonly present with severe neurological symptoms caused by brain infarction or hemorrhage. Histologically, the steno-occlusive process is based on fibrocellular thickening of intima and intimal smooth muscle cell proliferation. In the literature, extracranial arterial involvement, i.e. fibromuscular dysplasia of renal or pulmonary arteries, has been described in several cases of moyamoya disease. Our aim is to show a unique case of moyamoya disease associated with fibromuscular dysplasia affecting an uncommon site.

Czech medical personalities in Vienna during the 19th century.

During the entire 19th century, Czech lands (Bohemia and Moravia) were part of the Austrian Empire (from 1867, Austrian-Hungarian Monarchy). Obviously, there used to be quite frequent migration of Czechs of all social groups towards Austria, particularly to the capital Vienna. It is estimated that in the year 1900, from the 1.6 million inhabitants of Vienna, there were 250-300 thousand Czechs. And this tendency concerned also medicine. In this paper, the most important Czech-born medical personalities working in Vienna in the 19th century will be briefly presented-in pathology Wagner, Rokitansky, Kolletschka, and Dlauhy; in internal medicine Skoda, Oppolzer, Duchek, and Chvostek; in surgery Pitha and Albert; in physiology and ophthalmology Prohaska; in pediatrics Bednar; and in dermatology Hebra.

Right heart ventricle myocarditis induced by pulmonary thrombembolism.

Deep venous thrombosis and pulmonary thrombembolism are referred to as venous thrombembolism. Pulmonary thrombembolism affects the right ventricle. Two morphologically and clinically distinct conditions are distinguished according to change of blood pressure and speed of blood pressure increase in the pulmonary artery - acute and chronic cor pulmonale. Acute cor pulmonale develops during rapid increase (within seconds) of blood pressure in the pulmonary artery. Morphologically, the condition leads to dilatation of the right ventricle and clinically to sudden cardiac death or severe circulatory instability. Chronic cor pulmonale represents myocardial hypertrophy of the right ventricle as a response to the gradually increasing pressure in the pulmonary artery. Herein, we demonstrate a rare case report of right ventricular myocarditis in a 51-year-old woman with pulmonary thromboembolism and morphological signs of chronic pulmonary hypertension. This non-infectious myocarditis is histologically characterized by myocardial damage (myocytolysis) and dominant histiocytic and neutrophil infiltration accompanied by scanty T-lymphocytes. These inflammatory changes differ from those associated with myocardial infarction. The possible pathological mechanisms of right ventricular myocarditis induced by pulmonary thrombembolism are discussed.

Fibrin Clot Architecture in Acute Ischemic Stroke Treated With Mechanical Thrombectomy With Stent-Retrievers　- Cohort Study.

BACKGROUND: The composition of intra-arterial clots might influence the efficacy of mechanical thrombectomy (MT) in ischemic stroke (IS) due to the acute occlusions within large cerebral arteries. The aims were to assess the factors associated with blood clot structure and the impact of thromboembolus structure on MT using stent-retrievers in patients with acute large artery IS in the anterior circulation.Methods and Results:In an observational cohort study, we studied the components of intra-arterial clots retrieved from large cerebral arteries in 80 patients with acute IS treated with MT with or without i.v. thrombolysis (IVT). Histology of the clots was carried out without knowledge of the clinical findings, including the treatment methods. The components of the clots, their age, origin and semi-quantitative graded changes in the architecture of the fibrin components (e.g., "thinning") were compared via neuro-interventional, clinical and laboratory data. The most prominent changes in the architecture of the fibrin components in the thromboemboli were associated with IVT (applied in 44 patients; OR, 3.50; 95% CI: 1.21-10.10, P=0.02) and platelet count (OR, 2.94; 95% CI: 1.06-8.12, P=0.04). CONCLUSIONS: In patients with large artery IS treated with the MT using stent-retrievers, bridging therapy with IVT preceding MT and higher platelet count were associated with significant changes of the histological structure of blood clots.

Mast cells in calcific aortic stenosis.

In developed countries, calcific aortic stenosis (CAS) has become the most common acquired valvular disease and reason for aortic valve replacement. It is considered a form of atherosclerosis and, like the latter, of inflammatory origin, with presence in the calcified aortic valves of blood vessels, lymphatics, lymphocytes, plasma cells, histiocytes, and sometimes also of metaplastic bone tissue. This study is aimed at examining the presence of CD117 - positive mast cells in CAS. In 56 examined calcified aortic valves excised by cardiac surgery, mast cells were constantly present as a part of the polymorphous cellular infiltrate; in individual cases, their numbers were 1-90 (median 24). The numbers were significantly higher in the congenitally malformed/bicuspid valves (median 40) than in the tricuspid ones (median 20). In valves with presence of metaplastic bone, mast cells were significantly more numerous (median 42) than in those without metaplasia (median 20). In 12 normal aortic valves obtained at autopsies, the numbers of mast cells were 4-21 (median 11). Discussed is a possible role of mast cells in pathogenesis of CAS.

Sudden Death Due to Cystic Tumor of the Atrioventricular Node and Fibromuscular Dysplasia Involving Branches of the Coronary Arteries.

In this paper, we report the autopsy findings of a 42-year-old White male who was found deceased at his home by his brother in the early morning hours with a history of excessive alcohol consumption 1 day before his death. A medical record review revealed chronic alcohol use with alcohol dependence syndrome, hypertension, and cardiac arrhythmias by electrocardiogram 2 years prior. External examination revealed only a single bruise on the forehead. Internal examination revealed changes associated with chronic alcohol abuse and mild atherosclerosis. The lack of a cause of death at autopsy resulted in a dissection of the cardiac conduction system and the detection of a small cystic lesion at the atrioventricular node region. Microscopic examination revealed a cystic tumor of the atrioventricular node and fibromuscular dysplasia of the coronary artery branches near the sinoatrial and atrioventricular nodes. Based on the case history and autopsy findings, death was attributed to a fatal cardiac arrhythmia due to cystic tumor of the atrioventricular node with fibromuscular dysplasia of the coronary artery branches near the sinoatrial and atrioventricular nodes a possible contributing factor.

Multiple Giant Coronary Artery Aneurysms: A Rare Cause of Sudden Cardiac Death.

Multiple giant aneurysms involving the coronary arteries are uncommon and rarely reported. In the presented case, a 63-year-old man with poorly controlled hypertension died suddenly. Gross autopsy examination showed multiple giant thrombus-filled coronary artery aneurysms, atherosclerotic coronary artery disease, and cardiomegaly. Histological sections of the coronary aneurysms showed atherosclerotic changes with both organized and fresh thrombus. Giant coronary aneurysm is defined as a segmental enlargement of a coronary artery with a diameter exceeding 20 mm or more. The main etiology of this nebulous entity is attributed to atherosclerosis and inflammatory or inherited connective tissue disorders with the remainder being congenital, infectious, or idiopathic. Before its cataclysmic presentation, when ruptured or thrombosed, giant coronary aneurysm usually has a silent clinical course. Sudden death owing to giant multiple coronary aneurysms is rare and mandates careful classification of the aneurysms and prudent search for autoimmune-mediated or genetically based factors for subsequent ancillary autopsy studies.

Association of Atrial Fibrillation with Morphological and Electrophysiological Changes of the Atrial Myocardium.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. For long time it was considered as pure functional disorder, but in recent years, there were identified atrial locations, which are involved in the initiation and maintenance of this arrhythmia. These structural changes, so called remodelation, start at electric level and later they affect contractility and morphology. In this study we attempted to find a possible relation between morphological (scarring, amyloidosis, left atrial (LA) enlargement) and electrophysiological (ECG features) changes in patients with AF. We examined grossly and histologically 100 hearts of necropsy patients - 54 with a history of AF and 46 without AF. Premortem ECGs were evaluated. The patients with AF had significantly heavier heart, larger LA, more severely scarred myocardium of the LA and atrial septum, and more severe amyloidosis in both atria. Severity of amyloidosis was higher in LAs vs. right atria (RAs). Distribution of both fibrosis and amyloidosis was irregular. The most affected area was in the LA anterior wall. Patients with a history of AF and with most severe amyloidosis have more often abnormally long P waves. Finding of long P wave may contribute to diagnosis of a hitherto undisclosed atrial fibrillation.

[Morphological and electrophysiological changes of the heart atria in necropsy patients with atrial fibrillation - a pilot study]. / Morfologické a elektrofyziologické zmeny v srdecních síních zemrelých s fibrilací síní - pilotní studie.

Atrial fibrillation (AF), the most common supraventricular tachycardia, has a morphological base, so called remodelation of atrial myocardium, with its abnormal conduction pattern as a consequence. The remodelation regards electrical, contractile, and structural properties. In this pilot study we attempted to find relations between the myocardial morphological (scarring, amyloidosis, left atrial enlargement) and electrophysiological (ECG characteristics of the P-wave) changes in patients with AF. We examined 40 hearts of necropsy patients - 20 with a history of AF and 20 with no history of AF. Grossly, the heart weight and the size of the left atrium (LA) were evaluated. Histologically, 7 standard sites from the atria were examined. In each specimen, the degree of myocardial scarring and of deposition of isolated atrial amyloid (IAA) were assessed. We failed to show any significant difference in the P-wave pattern between patients with and without AF. Morphologically, however, there were several differences - the patients with AF had significantly heavier hearts, larger left atria, more severely scarred myocardium of the LA and the atrial septum, and more severe deposition of IAA in both atria in comparison to the control group of patients with sinus rhythm. The left atrial distribution of both fibrosis and amyloidosis was irregular. In patients with AF the former was most pronounced in the LA ceiling while the latter in the LA anterior wall. The entire series showed more marked amyloidosis in the left than in the right atrium. An interesting finding was the universal absence of IAA in the sinoatrial node. The knowledge of distribution of atrial myocardial structural changes could be utilized by pathologists in taking specimens for histology and also by cardiologists in targeting the radiofrequency ablation therapy.