Systemic cobalt toxicity from total hip arthroplasties: review of a rare condition Part 1 - history, mechanism, measurements, and pathophysiology.

UNLABELLED: Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging. The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation. The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity. This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties. TAKE HOME MESSAGE: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications.

Systemic cobalt toxicity from total hip arthroplasties: review of a rare condition Part 2. measurement, risk factors, and step-wise approach to treatment.

UNLABELLED: As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 µg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity. TAKE HOME MESSAGE: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately.

Primary intimal (spindle cell) sarcoma of the heart: a case report and review of the literature.

Intimal (spindle cell) sarcomas of the left atrium are extremely rare primary cardiac tumours with three cases reported (Li et al. (2013), Cho et al. (2006), and Modi et al. (2009)). We present a 69-year-old man who first came to medical attention after experiencing abdominal discomfort. He had a 30 lb weight loss apparently due to dieting. He denied any other constitutional symptoms. His symptoms persisted despite a course of antibiotics for presumed diverticulitis. Laboratory values were within normal limits, though the haemoglobin was 131 g/L (normal: 140-180). Subsequent abdominal computed tomography (CT) scan revealed an abdominal wall mass and intracardiac lesion; the cardiac mass was further characterized by transesophageal echo (TEE), magnetic resonance imaging (MRI), and dedicated cardiac CT. TEE revealed a mass attached to the posterolateral wall of the left atrium above the mitral annulus, and the cardiac CT and MRI confirmed the TEE findings. The patient underwent extensive surgical resection and repair of the left side of the heart. Postoperatively, he developed acute renal failure requiring dialysis and reintubation for volume overload. He became acutely hypotensive, developed multiorgan failure, and succumbed to his illness. Histopathologic examination of the left atrial mass showed an intimal sarcoma.

Atrial masses post cardiac transplantation: diagnostic and treatment dilemmas.

Atrial masses postcardiac transplant are not well reported and their diagnosis and treatment can be challenging. In the asymptomatic patient, differentiating thrombus from cardiac tumor can sometimes be difficult and the use of multiple imaging modalities is recommended. Accurate diagnosis is imperative to inform a treatment plan that balances the benefits and risks of a medical versus surgical approach. We present three cases of atrial masses postcardiac transplant to illustrate this clinical dilemma.

Cardiac Pathology in Glycogen Storage Disease Type III.

PURPOSE: To investigate the distribution and clinical impact of glycogen accumulation on heart structure and function in individuals with GSD III. METHODS: We examined cardiac tissue and the clinical records of three individuals with GSD IIIa who died or underwent cardiac transplantation. Of the two patients that died, one was from infection and the other was from sudden cardiac death. The third patient required cardiac transplantation for end-stage heart failure with severe hypertrophic cardiomyopathy. RESULTS: Macro- and microscopic examination revealed cardiac fibrosis (n = 1), moderate to severe vacuolation of cardiac myocytes (n = 3), mild to severe glycogen accumulation in the atrioventricular (AV) node (n = 3), and glycogen accumulation in smooth muscle cells of intramyocardial arteries associated with smooth muscle hyperplasia and profoundly thickened vascular walls (n = 1). CONCLUSION: Our findings document diffuse though variable involvement of cardiac structures in GSD III patients. Furthermore, our results also show a potential for serious arrhythmia and symptomatic heart failure in some GSD III patients, and this should be considered when managing this patient population.

Heart transplant biopsies: interpretation and significance.

The endomyocardial biopsy (EMB) is a valuable tool that is inadequately utilised, except in monitoring orthotopic, homograft, heart grafts. Performed on a regular, programmed schedule, or on an emergent basis when needed, the EMB is the gold standard for monitoring graft function ( with regard to cellular rejection), often before clinical symptoms develop. This paper addresses these points and discusses handling of tissues and some studies for possible antibody mediated rejection when the lack of morphologic features of cellular rejection does not fit with the patients clinical presentation, days or months after the surgical procedure. In the hands of a skilled operator the EMB procedure is relatively painless and free of significant complications.

Multifocal "tapete" papillary fibroelastoma.

Papillary fibroelastomas (PFEs) are benign cardiac tumours that typically arise on diseased aortic or mitral valves. Usually solitary, PFEs are characterised by numerous frond-like branches attached to the valve surface by a single stalk, elastic tissue present within the central core, and the appearance of a sea anemone when immersed in water. PFEs have a predilection for men with a mean age of 56 years. A very rare case of a 25-year-old man with multiple lesions on the aortic and mitral valves and a large confluent "carpet-like" lesion in the left ventricular cavity is presented. Admitted with a significant left middle cerebral artery stroke and hemiplegia, investigations showed a left ventricular outflow tract lesion, with surgical excision displaying a multifocal "carpet-like" PFE. Histopathological examination showed various lesions presenting with a short stem, several fronds arising from each stem like a "tree trunk", and elastic tissue within the central core. This case is presented, along with a review of 833 reported cases of PFEs published after the year 2001. It is believed that this is the first reported instance of surgically resected and morphologically confirmed multiple PFEs seen and removed at one operation.

Drug-related cardiac pathology.

Many commonly used drugs, with each causing changes that may be potentially lethal, can adversely affect the function of the heart. In addition some drugs have synergistic effects that can also damage cardiovascular tissues. The drug-related cardiotoxic effects of antineoplastic agents, psychotropic medications, heavy metals, substances of abuse, promotility agents, antihistamines, antimicrobials and antiarrhythmic agents are discussed. Hypersensitivity myocarditis is also discussed.

SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS.

BACKGROUND: Angiotensin converting enzyme 2 (ACE2), a monocarboxylase that degrades angiotensin II to angiotensin 1-7, is also the functional receptor for severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and is highly expressed in the lungs and heart. Patients with SARS also suffered from cardiac disease including arrhythmias, sudden cardiac death, and systolic and diastolic dysfunction. MATERIALS AND METHODS: We studied mice infected with the human strain of the SARS-CoV and encephalomyocarditis virus and examined ACE2 mRNA and protein expression. Autopsy heart samples from patients who succumbed to the SARS crisis in Toronto (Canada) were used to investigate the impact of SARS on myocardial structure, inflammation and ACE2 protein expression. RESULTS: Pulmonary infection with the human SARS-CoV in mice led to an ACE2-dependent myocardial infection with a marked decrease in ACE2 expression confirming a critical role of ACE2 in mediating SARS-CoV infection in the heart. The SARS-CoV viral RNA was detected in 35% (7/20) of autopsied human heart samples obtained from patients who succumbed to the SARS crisis during the Toronto SARS outbreak. Macrophage-specific staining showed a marked increase in macrophage infiltration with evidence of myocardial damage in patients who had SARS-CoV in their hearts. The presence of SARS-CoV in the heart was also associated with marked reductions in ACE2 protein expression. CONCLUSIONS: Our data show that SARS-CoV can mediate myocardial inflammation and damage associated with down-regulation of myocardial ACE2 system, which may be responsible for the myocardial dysfunction and adverse cardiac outcomes in patients with SARS.

Mitral valve-sparing procedures and prosthetic heart valve failure: a case report.

Prosthetic heart valve dysfunction due to thrombus or pannus formation can be a life-threatening complication. The present report describes a 47-year-old woman who developed valvular cardiomyopathy after chorda-sparing mitral valve replacement, and subsequently underwent heart transplantation for progressive heart failure. The explanted mitral valve prosthesis showed significant thrombus and pannus leading to reduced leaflet mobility and valvular stenosis. The present report illustrates the role of the subvalvular apparatus and pannus in prosthesis dysfunction.

Intracranial arterial wall imaging using high-resolution 3-tesla contrast-enhanced MRI.

BACKGROUND: Conventional arterial imaging focuses on the vessel lumen but lacks specificity because different pathologies produce similar luminal defects. Wall imaging can characterize extracranial arterial pathology, but imaging intracranial walls has been limited by resolution and signal constraints. Higher-field scanners may improve visualization of these smaller vessels. METHODS: Three-tesla contrast-enhanced MRI was used to study the intracranial arteries from a consecutive series of patients at a tertiary stroke center. RESULTS: Multiplanar T2-weighted fast spin echo and multiplanar T1 fluid-attenuated inversion recovery precontrast and postcontrast images were acquired in 37 patients with focal neurologic deficits. Clinical diagnoses included atherosclerotic disease (13), CNS inflammatory disease (3), dissections (3), aneurysms (3), moyamoya syndrome (2), cavernous angioma (1), extracranial source of stroke (5), and no definitive clinical diagnosis (7). Twelve of 13 with atherosclerotic disease had focal, eccentric vessel wall enhancement, 10 of whom had enhancement only in the vessel supplying the area of ischemic injury. Two of 3 with inflammatory diseases had diffuse, concentric vessel wall enhancement. Three of 3 with dissection showed bright signal on T1, and 2 had irregular wall enhancement with a flap and dual lumen. CONCLUSIONS: Three-tesla contrast-enhanced MRI can be used to study the wall of intracranial blood vessels. T2 and precontrast and postcontrast T1 fluid-attenuated inversion recovery images at 3 tesla may be able to differentiate enhancement patterns of intracranial atherosclerotic plaques (eccentric), inflammation (concentric), and other wall pathologies. Prospective studies are required to determine the sensitivity and specificity of arterial wall imaging for distinguishing the range of pathologic conditions affecting cerebral vasculature.

Dilated cardiomyopathy: a review.

Dilated cardiomyopathy (DCM) is a common cardiac diagnosis that may result as a consequence of a variety of pathologies. The differential diagnosis remains quite broad since many pathologies can present as DCM, and as a result the approach to diagnosis may, at times, be quite difficult. This review article discusses genetic and acquired causes of DCM, pathophysiology of myocardial damage, pathology, and diagnostic criteria. An approach to management is also included, in the hope of informing physicians of a clinical entity that afflicts a substantial number of people worldwide.

Hypertrophic cardiomyopathy: current understanding and treatment objectives.

The understanding of hypertrophic cardiomyopathy (HCM) has changed dramatically over the last few decades, and it is now understood to be caused by a mutation in one of several cardiac sarcomeric genes. Due to complications such as outflow tract obstruction, diastolic dysfunction, arrhythmias, stroke, infective endocarditis and sudden cardiac death, appropriate and early identification of these patients is imperative. This review attempts to summarise the current state of knowledge on HCM, and provide insight of the appropriate investigations needed in patients with HCM. It also outlines treatment strategies for these patients. Much remains unknown about this complex and intriguing disease, and continued research in identifying the genetic basis of HCM, along with the assessment of therapeutic strategies, will help to optimise patient care.

Aortic stent grafts.

Abdominal aortic aneurysms (AAAs) occur when weakened areas of the abdominal aortic wall result in a ballooning of the blood vessel. Attributed risk factors include smoking, atherosclerosis and hypertension. Traditionally, AAAs were treated with open surgery, involving a large abdominal incision and the placement of a synthetic graft. The introduction of endovascular aneurysm repair (EVAR) however, proved to have many advantages over open repair, chief among which is a lower perioperative morbidity and mortality rate. EVAR is likely to continue to evolve and the complications associated with this procedure will likely continue to decrease. In the meantime, the benefit of the continued, detailed analyses of explanted devices is twofold: (1) for future development of new devices; and (2) cognisance of complications that arise with any new device. This review is a guide to the many FDA approved stents which are commercially available, and those likely to become available following clinical trials.

Variation in the histopathological features of patients with ascending aortic aneurysms: a study of 111 surgically excised cases.

BACKGROUND: Ascending aortic aneurysms (AA) are a common, though poorly understood medical condition. AIMS: To document the histological changes in a large series of human ascending AA, and to correlate these changes with clinical variables. METHODS: 111 ascending AA were excised at surgery over a 3 year period. Each aneurysm was received as a continuous ring of tissue. Sections were taken from the anterior, posterior, greater and lesser curvature of the aorta and graded in a semi-quantitative fashion for the degree of elastin fragmentation, elastin loss, smooth muscle cell (SMC) loss, intimal changes and inflammation. RESULTS: Mean patient age at surgery was 58.7 (15.6) years; there were 70 men and 41 women. 12 patients had Marfan syndrome, 34 (30.6%) had a bicuspid aortic valve (BAV), while 71 (64.0%) had a tricuspid aortic valve (TAV). Inflammatory cells were present in 28 cases (25.2%) and were confined to the adventitia. No particular region of the aortic circumference was more severely affected, however a BAV was associated with significantly less intimal change, and less fragmentation and loss of elastic tissue compared with patients with a TAV. Advanced age (>65 years), female gender and Marfan syndrome were all associated with more severe elastin degeneration and smooth muscle cell loss (p<0.05 for all). CONCLUSION: Results indicate a wide variation in the histological appearance in ascending AA, depending on patient characteristics. They suggest that the underlying aneurysm pathogenesis may also be highly variable; this warrants further investigation.

Implications of a congenitally abnormal valve: a study of 1025 consecutively excised aortic valves.

BACKGROUND: An increasing proportion of patients with congenitally abnormal aortic valves (AV) present for AV replacement. AIMS: To review morphological changes in a large contemporary patient population undergoing AV replacement. METHODS: A detailed review was conducted for all 1025 patients who underwent AV replacement from 2002 to 2005, including the clinical indication for surgery, the type of native AV disease, the pathological changes observed in each valve and the need for related surgery. RESULTS: Tricuspid (TAV), bicuspid (BAV) and unicuspid (UAV) aortic valves were observed in 64.5%, 31.9% and 3.0% of all patients respectively. A decreased number of cusps was associated with increasing predilection for male gender (83.9%, 73.4%, 59.2% for UAV, BAV, TAV respectively), a younger patient age at surgery (41.6 (14.3), 61.3 (12.8), 67.5 (12.9) years), and an increased occurrence of pathological changes in the cusps, including calcification of both the cusp and the base, ossification and ulceration. UAV and BAV were also associated with increasing replacement of the ascending aorta due to dilatation and aneurysm formation (54.8, 38.8%, 16.6%). The incidence of infective endocarditis and rheumatic heart disease was 3.8% and 11.2% of all excised valves respectively. CONCLUSION: UAV and BAV were increasingly likely to affect men, fail at an earlier age, and show an increasing incidence of pathological changes in the cusps and ascending aorta than TAV. These results suggest that TAV, BAV and UAV may represent a phenotypic continuum of a similar disease process.

An approach to endomyocardial biopsy interpretation.

The endomyocardial biopsy (EMB) remains the gold standard mode of investigation for diagnosing many primary and secondary cardiac conditions. Through a percutaneous and transvenous route, tissue fragments are generally procured from the right ventricular septum, with very few complications. Widespread use of EMB followed the development of heart transplantation as a means to follow allograft rejection. It has since been useful in helping to diagnose conditions affecting the heart, including cardiomyopathies, myocarditis, infiltrative lesions, arrhythmias, and drug toxicities. The procedure has also been used as a research tool to investigate the natural history of disease and the cardiotoxicity of new medications. This review presents an approach to the evaluation of the EMB, which is particularly directed towards those who may be asked to interpret such biopsies, but are not dedicated cardiovascular pathologists. Through a systematic evaluation of the endocardium, myocardium, interstitium, and intramural vessels, in the context of a complete clinical history, enough information can be deduced to diagnose or exclude specific conditions of clinical value.

Coronary artery stents: identification and evaluation.

First introduced in the 1980s, the coronary stent has been used to reduce the rate of arterial restenosis. Coronary stent implantation is currently a common procedure performed by interventional cardiologists, and the market for development and design is constantly expanding and evolving. This article was designed to assist pathologists in the accurate identification of coronary stents that are currently available, in addition to some that are no longer being implanted. The stents reviewed here were chosen based on frequency of use and/or occurrence in the literature. Some of the newer models have yet to undergo extensive clinical testing. The summaries accompanying each stent include concise physical descriptions and documented complications, intended to serve as a guide for the investigating pathologist.

Analysis of prosthetic cardiac devices: a guide for the practising pathologist.

Pathologists all over the world increasingly encounter prosthetic cardiac devices. A good evaluation of these devices is a valuable source of information, which can contribute to patient care and the appreciation and understanding of the pathobiology involved in the changes occurring between the host and the implanted prosthetic device. This article summarises the considerations underlying the analysis of prosthetic devices (particularly prosthetic heart valves), including the identification of the devices, the major morphological features of the devices, their modes of failure, and some technical details about evaluation and pitfalls.