Of Mouse and Man: Cross-Species Characterization of Hypertensive Cardiac Remodeling.

Hypertension is a major public health concern and poses a significant risk for sudden cardiac death (SCD). However, the characterisation of human tissues tends to be macroscopic, with little appreciation for the quantification of the pathological remodelling responsible for the advancement of the disease. While the components of hypertensive remodelling are well established, the timeline and comparative quantification of pathological changes in hypertension have not been shown before. Here, we sought to identify the phasing of cardiac remodelling with hypertension using post-mortem tissue from SCD patients with early and advanced hypertensive heart disease (HHD). In order to study and quantify the progression of phenotypic changes, human specimens were contrasted to a well-described angiotensin-II-mediated hypertensive mouse model. While cardiomyocyte hypertrophy is an early adaptive response in the mouse that stabilises in established hypertension and declines as the disease progresses, this finding did not translate to the human setting. In contrast, optimising fibrosis quantification methods and applying them to each setting identified perivascular fibrosis as the prevailing possible cause for overall disease progression. Indeed, assessing myocardial inflammation highlights CD45+ inflammatory cell infiltration that precedes fibrosis and is an early-phase event in response to elevated arterial pressures that may underscore perivascular remodelling. Along with aetiology insight, we highlight cross-species comparison for quantification of cardiac remodelling in human hypertension. As such, this platform could assist with the development of therapies specific to the disease phase rather than targeting global components of hypertension, such as blood pressure lowering.

The role of endocarditis in sudden cardiac death: highlighting the value of the autopsy, pathological features and cardiac complications.

OBJECTIVE: Endocarditis is increasing in incidence due to growing numbers of cardiac interventions, valve replacements and immunosuppressants. It can be difficult to diagnose clinically, has high mortality and can present as sudden cardiac death (SCD) with few/subtle preceding symptoms. True incidence of SCD related to endocarditis is unknown. METHODS: Retrospective analysis of UK national database of 6000 cases of SCD, 1994-2020, for "endocarditis" as cause of death. RESULTS: Of 30 cases (0.50%), 19(63%) were male and mean age was 36.2 ± 20.1 years. Postmortem examination showed the aortic valve was solely affected in 13 (43%), mitral in 9 (30%), tricuspid in 2(6.7%) and pulmonary in 1 (3.3%). Three cases (10%) had more than one valve affected and 2 (6.7%) were nonvalvular affecting the ascending aorta. Vegetations ranged from small easily missed irregularities to large fungating masses. Ten (33%) patients developed aortic abscesses, 2 of which had aneurysms, 13 (43%) had coronary artery septic emboli with micro-abscesses and myocardial microinfarction, and 2 (6.7%) were healed endocarditis with perforation and regurgitation with ventricular remodeling. Thirteen (43%) had an identifiable underlying valve abnormality or replacement, most common being a bicuspid aortic valve (7; 54%). CONCLUSIONS: This study highlights that although rare, endocarditis is an important cause of SCD in those with normal valves, valvular disease and valve replacement surgery. Absence of a premortem diagnosis in 70% of our cohort highlights the need for detailed analysis of the heart and cardiac valves at autopsy. Gross appearance of vegetations varies widely and can be missed. Awareness of associated cardiac complications is required for elucidation of the cause of death and will provide valuable lessons for clinicians.

Insights from examination of hearts from adults dying suddenly to the understanding of congenital cardiac malformations.

Congenital heart disease is a rare but important finding in adults who experience sudden death. Examination of the congenitally malformed heart has historically been considered esoteric and best left to those with expertise. The Cardiac Risk in the Young cardiovascular pathology laboratory based at St George's University of London has now received over 6,000 cases. Of these, 21 congenitally malformed hearts were retained for research and educational purposes. Hearts were assessed using sequential segmental analysis, and causes of death were adjudicated based on thorough macroscopic examination and histology. Congenital malformations that were encountered included atrial septal defects, ventricular septal defects, tetralogy of Fallot, and transposition of the great arteries in both its regular and congenitally corrected variants. Findings also included hearts with mirror-imaged and isomeric atrial appendages. Direct causes of death included myocardial fibrosis, pulmonary hypertension, and hemorrhage. A small but notable proportion did not reveal a substrate for arrhythmia, raising the question of whether the terminal event was due to the congenital heart disease itself, or an underlying channelopathy. Here, we demonstrate the value of simple sequential segmental analysis in describing and categorizing the cases, with the concept of the "morphological method" serving to identify the distinguishing features of the cardiac components. Clin. Anat. 33:394-404, 2020. © 2019 Wiley Periodicals, Inc.

Primary Ovarian Malignant PEComa: A Case Report.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm characterized by expression of both melanocytic and smooth muscle markers. PEComas are rarely encountered in the female genital tract. We report a case of malignant primary PEComa of the ovary, and discuss the differential diagnosis. This represents the first case of primary typical malignant PEComa of the ovary.