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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.

ABSTRACTPericardial access, predominantly utilized for emergency treatment, has evolved as an important approach for performing cardiac interventions. Accordingly, the complex anatomy and unique physiology of the pericardium need to be well understood for procedural success. This understanding is important to not only plan and guide interventions but also to inform complications and morbidity associated with post-cardiac injury syndromes. In these circumstances, multi-modality imaging has an increasingly central role. Therefore, the aims of this review are to provide an overview of procedurally relevant pericardial anatomy and focus on important imaging assessments as they relate to the increased use of pericardial access for intervention and possible consequences in patients who develop post-cardiac injury pericarditis.

Cardiovascular disease occurs in 6.5 to 6.8 percent of patients infected with the human immunodeficiency virus (HIV). In many cases, this cardiovascular disease is the result of some opportunistic infection, which may be viral, bacterial, protozoal, or fungal. However, in some cases the cardiovascular disease seems to be the result of intrinsic changes in the heart muscle itself. Some studies have claimed to find HIV within the heart muscle cells, while other studies have failed to confirm this. The current study used the sensitive polymerase chain reaction to detect the presence of HIV in cells dissected from biopsy specimens of HIV-infected patients. Fifteen patients were enrolled in the study. Five of these patients had symptoms that suggested the presence of a heart abnormality, while the remaining 10 patients did not. Biopsies were taken from the inside of the heart and were dissected to separate the myocytes, or muscle cells, from the dendritic (nerve) cells of the heart muscle. Gene sequences indicative of the presence of HIV could be confirmed in 2 of the 5 myocyte specimens taken from patients with cardiac symptoms and in 6 of 10 patients without symptoms. Similarly, HIV could be detected in the dendritic cells of all 5 symptomatic patients and in 8 of the 10 patients without symptoms. These results suggest that the heart cells themselves are infected with HIV in many HIV-infected patients. However, infection with HIV does not seem to be correlated with heart symptoms, suggesting that some other factor in addition to HIV is necessary for the development of symptomatic heart abnormalities. (Consumer Summary produced by Reliance Medical Information, Inc.)

This study sought to determine the accuracy of the pre-transplantation clinical diagnosis of heart disease in the United Network for Organ Sharing (UNOS) database.

Background: Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. Case Report: A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Conclusion: Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis., INTRODUCTION Ephedra (Ma Huang) is a popular herbal product originating from China which contains from 0.5% to 2.5% sympathomimetic alkaloid (primarily ephedrine and pseudoephedrine). While cardiotoxicity is usually due to [...]

Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic vasculopathy that usually affects the carotid and renal arteries. We have observed FMD-like vascular changes in specimens resected for ischemia or Crohn’s disease (CD). On the basis of a systematic clinicopathologic review of these 11 cases identified between 1982 and 2014, we describe a distinct mesenteric vasculopathy that involves both arteries and veins [mesenteric arteriovenous dysplasia/vasculopathy (MAVD/V)] and is characterized by (1) concentric/eccentric smooth muscle collarette around the tunica media of both the artery and the vein in ≥2 foci, (2) varying degrees of intimal and medial hyperplasia and adventitial fibrosis, and (3) lack of inflammation or thrombi. MAVD/V cases were clinically diagnosed as CD (45%), mass/lesion (27%), ischemia (9%), obstruction (9%), or rectal prolapse (9%). Abdominal pain for >1 year was the most common symptom. Most patients were women (M:F=1:2.7; mean age, 63 y). Mucosal changes mimicking CD, such as architectural distortion (55%), multifocal ulcers (73%), and pyloric gland metaplasia (64%), were common; however, no granulomas or transmural lymphoid aggregates were identified. Ischemic pattern of injury was seen in 4 cases. Upon follow-up (mean, 31.2 mo), 8 patients were found to be asymptomatic, 2 had died of unrelated causes, and 1 was lost to follow-up. We propose the name MAVD/V for a distinct noninflammatory, nonatherosclerotic, localized form of mesenteric vasculopathy that involves both arteries and veins, distinct from FMD. Unlike FMD, surgical resection appears to be curative, with a favorable clinical outcome. Awareness of this vascular entity is important as patients may be potentially misdiagnosed as having CD and ischemic bowel disease.

Bioprosthetic valves are increasingly implanted, with generally consistent and durable results. Early bioprosthetic valve failure is uncommon, and most clinicians are unfamiliar with the spectrum of early structural complications involving bioprostheses. In this review, the authors organize causes of early bioprosthetic valve failure according to possible pathogenesis, demonstrate the correlation between echocardiographic and anatomic findings, and discuss potential treatments. First, they address early bioprosthetic valve stenosis secondary to thrombosis. Next, they discuss excessive pannus formation, a hitherto rarely described cause of early bioprosthetic valve failure. Finally, the authors address early structural valve deterioration mediated by calcification or primary tears. Illustrative examples with relevant echocardiographic and operative findings are provided.

Autosomal dominant retinocerebral vasculopathy with cerebral leukodystrophy (RVCL) is a rare neurovascular syndrome causing retinal and central nervous system vasculopathy often recognized as contrast-enhancing white matter changes or pseudotumors on imaging. Heterozygous frameshift mutations in the 3-prime repair exonuclease 1 gene have been identified in families affected by RVCL. Variable light microscopic findings and a characteristic ultrastructural appearance of the vasculature in the brain have been reported. Description of the ophthalmic histopathology is exceedingly rare. Here, we report previously undescribed bilateral eye findings in a patient diagnosed with RVCL. The ophthalmic pathology includes thickening and reduplication of the retinal capillary basal lamina demonstrated by electron microscopy. These findings expand what is known about this disease and help further delineate its phenotype.

Currently clinical antibody-mediated rejection (AMR) requires demonstration of histopathologic changes, presence of donor-specific allo-antibodies and allograft dysfunction to establish the diagnosis. Pathology practice patterns in the immunopathologic evaluation and interpretation of cardiac transplant biopsies vary. Specific recommendations for post-transplant allo-antibody monitoring are lacking. Recently, the occurrence of surveillance biopsies being positive for immunopathologic markers of AMR without concomitant graft dysfunction is increasingly recognized. This review focuses on issues of standardization in the diagnosis of AMR and the need for updated criteria.

Atherosclerosis results in a considerable medical and socioeconomic impact on society. We sought to evaluate novel magnetic resonance imaging (MRI) angiography and vessel wall sequences to visualize and quantify different morphologic stages of atherosclerosis in a Watanabe hereditary hyperlipidemic (WHHL) rabbit model.

BackgroundA 56-year-old man with normal cardiac function received treatment with interferon α-2b for malignant melanoma. Eight months after the initiation of therapy he developed fatigue and dyspnea on exertion. Two months later, he was admitted to hospital with ORTHOPNEA, worsening dyspnea and cough. Physical examination findings were consistent with congestive heart failure. Laboratory studies were notable for hypothyroidism. Echocardiography revealed severe, global left-ventricular dysfunction.

Complement is a multifunctional system of receptors and regulators as well as effector molecules. Both the pathogenic and diagnostic power of complement is based on the capacity of the complement system to amplify innate and adaptive immunity. This amplification is accomplished through two strategies: (1) enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes, platelets and parenchymal cells through specific receptors or receptor‐independent pore formation. The mechanisms by which complement mediates and modifies nonspecific inflammation, antibody‐mediated injury and T‐cell responses are of particular significance to the pathogenesis of transplant rejection. Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection.

We investigated the effects of 3-nitropropionic acid (3NPA), a previously characterized neurotoxin, in four strains of mice to better understand the molecular basis of variable host responses to this agent. Unexpectedly, we found significant cardiac toxicity that always accompanied the neurotoxicity in all strains of mice in acute and subacute/chronic toxicity testing. Caudate putamen infarction never occurred without cardiac toxicity. All mouse strains tested are sensitive to 3NPA although the C57BL/6 and BALB/c mice require more exposure than 129SVEMS and FVB/n mice. Cardiac toxicity alone was found in 50% of symptomatic mice tested and morphologically, the cardiac toxicity is characterized by diffuse swelling of cardiomyocytes and multifocal coagulative contraction band necrosis. In subacute to chronic exposure, atrial thrombosis, cardiac mineralization, cell loss, and fibrosis are combined with cardiomyocyte swelling and necrosis. Ultrastructurally, mitochondrial swelling occurs initially, followed by disruption of myofilaments. Biochemically, isolated heart mitochondria from the highly sensitive 129SVEMS mice have a significant reduction of succinate dehydrogenase activity, succinate oxygen consumption rates, and heart adenosine triphosphate after 3NPA treatment. The severity of morphological changes parallels the biochemical alterations caused by 3NPA, consistent with cardiac toxicity being a consequence of the effects of 3NPA on succinate dehydrogenase. These experiments show, for the first time, that 3NPA has important cardiotoxic effects as well as neurotoxic effects, and that cardiac toxicity possibly resulting from inhibition of the succinate dehydrogenase in heart mitochondria, contributes to the cause of death in 3NPA poisoning in acute and subacute/chronic studies in mice.

Damage to the posterolateral wall of the left ventricle was found in eight of approximately 700 sheep undergoing mitral valvular replacement as part of animal model studies of bioprosthetic valves. The damage consisted of left ventricular aneurysms in five animals, subacute rupture of the left ventricle in one, acute left ventricular laceration in one, and endocardial scarring in one. Six of the eight bioprostheses were bovine pericardial valves, including five low-profile valves and one standard valve; of the two porcine bioprostheses, one was intentionally oversized and the other was a low-profile supra-annular valve. In each of these animals the damage appeared to have been caused by contact between the most posterior strut of the bioprosthesis and the left ventricular wall.

The objective of this study was to determine the early influence of platelet inhibition on the histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. Cephalic vein grafts were interposed bilaterally in the femoral arteries of 15 stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. All animals received in combination aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Grafts were excised from five animals for analysis on each of postoperative days 3, 7, 14, 30, 60, and 90. In animals subjected to platelet inhibition, cholesterol content in the graft was 170 ± 52 μg/100 mg at 90 days, 205% of the level in ungrafted vein (p < 0.01). This change was small in comparison with the increase to 686% of ungrafted vein observed in our study of control animals. In stepwise regression analysis, cholesterol content of grafts was best predicted by prevalence of foam cells (r2= 0.82), and the proportion of intima as a fraction of total wall area was best predicted by the presence of macrophages (r2= 0.69). Platelet inhibition did not decrease the extent of intimal hyperplasia. The prevalence of adherent platelets (r = -0.72) and the amount of fibrin (r = -0.78) correlated inversely with the amount of endothelium present during the first 14 days. The strength of these correlations declined with time, despite persistent lack of endothelium in some areas. Medial fibrosis occurred to the same extent as in control grafts, as did the early appearance of platelet factor VIII and fibronectin and the lack of vasa vasorum at 3 days followed by reappearance at 7 days. These data demonstrate that platelet inhibition dramatically reduces lipid uptake by grafts in the first 90 days but has less influence over histologic or morphometric changes.

Complement activation contributes to antibody-mediated allograft rejection, but increasing evidence also implicates complement proteins produced locally within the graft, in part by infiltrating mononuclear cells, as important mediators of tissue injury. To test this concept in transplant recipients, we evaluated complement, complement regulator, and T cell/proinflammatory marker gene expression by quantitative real-time polymerase chain reaction in 71 archived heart transplant biopsies and correlated the results with the histologic grade of rejection. Significantly more transcripts encoding alternative pathway components factor B, C3 and properdin, and C3a receptor and C5a receptor were detected in grade 3 versus grade 0 or 1 biopsies. The grade 3 rejections also contained significantly higher amounts of CD3, interferon , perforin, and granzyme B genes. In addition to providing supportive evidence for a pathogenic role of graft-derived complement in human heart transplant injury, these correlations suggest that molecular profiling of complement gene expression could be useful in the diagnosis of human allograft rejection.

We report a case of syphilitic aortitis suspected by the intraoperative appearance of the aorta. Diagnosis was confirmed by postoperative serological testing. Given the recent increase in the number of cases of primary syphilis, it is important to remain aware of the clinical and pathological manifestations of tertiary syphilis.

Objective: It is increasingly recognized that cardiac amyloidosis can occur in patients with severe aortic stenosis undergoing both surgical and transcatheter valve replacements. We aimed to investigate whether unrecognized cardiac amyloidosis may also occur in patients with severe mitral valve disease undergoing surgery., Methods: The pathology department database at our center was retrospectively analyzed over a 10-year period for cases in which the mitral valve or another type of cardiac tissue removed at the time of mitral surgery demonstrated incidental amyloidosis. Clinical and echocardiographic variables were collected from the electronic medical record and the echocardiographic database., Results: Between 2007 and 2016, a total of 7,733 mitral valve surgical specimens were received. Of these, there were 15 cases in which the mitral valve, or another type of cardiac tissue removed at surgery, demonstrated incidentally detected amyloidosis. The most frequent comorbidities were hypertension (87%) and atrial fibrillation (80%); 13 patients (87%) underwent bioprosthetic mitral valve replacement, and 2 patients (13%) underwent mitral valve repair. Sites of amyloid deposition were the mitral valve (80%), left atrial appendage (33%), and subaortic tissue (7%); 14 patients (93%) had wild-type transthyretin amyloid. The mean duration of follow-up was 1,023 days (range: 29-2,811 days). There were no surgical complications in the follow-up period., Conclusions: Over a 10-year period, incidentally detected cardiac amyloidosis occurred in 0.2% of the mitral valve surgical cases. The outcomes for these patients undergoing mitral valve surgery were excellent, with no complications or deaths attributable to surgery at a mean follow-up of 1,023 days., (© 2019 S. Karger AG, Basel.)