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.

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.

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.

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.

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.

Conditioned nutritional deficiencies in the cardiomyopathic hamster heart.

BACKGROUND: Evidence indicates that nutritional factors may be important in the maintenance of myocyte structure and energetics. The failing myocardium has been reported to exhibit a depletion of several nutrients that are important for the maintenance of intracellular calcium homeostasis and cellular energetics, and levels of oxidative stress. This nutrient depletion may contribute to the progressive deterioration in myocardial structure and function observed in heart failure. OBJECTIVE: To examine the extent to which advanced cardiomyopathy results in a depletion of nutrients and/or metabolites and antioxidants, and whether supplementation with these nutrients may influence cellular structure or function. SUBJECTS AND METHODS: Cardiomyopathic hamsters were randomly placed to one of the three following diet groups: chow; control gelled diet; or a supplemented gelled diet that provided taurine, carnitine, coenzyme Q10, selenium, vitamins E and C, creatine, thiamine and L-cysteine. After approximately three months of supplementation, one group of hamsters underwent functional testing using a modified Langendorff technique with biopsy samples taken for electron microscopy. Myocardial nutrient concentrations were determined in a second group of diseased and nondiseased hamsters of the same age. RESULTS: Cardiomyopathy resulted in a depletion of vitamin E, creatine, carnitine, taurine and coenzyme Q10. Supplementation resulted in improved cardiac ultrastructure, function and contractility compared with nonsupplemented hamsters. CONCLUSIONS: These studies suggest that heart failure results in 'condition-related nutrient deficiencies' that, once corrected, can significantly impact on heart function and structure.

The failure modes of biological prosthetic heart valves.

Bioprosthetic heart valves have been used since the 1960s, starting with the use of homograft aortic valves obtained from human cadavers. Today prosthetic heart valves are used widely, and bioprostheses account for close to 40% of all heart-valve replacements. Although most bioprosthesis are still stented porcine aortic valves, the introduction of stentless valves and the increasing use of cryopreserved homograft valves has led to an upsurge of interest in bioprosthesis. There have been significant changes in the handling and fixation of porcine aortic valves; however, their modes of failure remain virtually unchanged, although many bioprosthetic valves now last for considerably longer periods. This article reviews the modes of failure of bioprosthetic heart valves.

In-vivo assessment of a photofixed bovine pericardial valve.

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the preclinical safety of a bioprosthetic cardiac valve in a large-animal model. The experimental pericardial valve was treated with a dye-mediated photooxidation process (PhotoFix) to enhance durability, and to reduce bioreactivity and mineralization potential. METHODS: Ten experimental (Sulzer Carbomedics PhotoFix pericardial valves, 25 mm) and three control valves (Carpentier-Edwards 2700, 25 mm) were placed in the mitral position of 13 juvenile sheep. Assessment criteria included animal survival, hematological analysis, host response, valve calcification and tissue stability. RESULTS: No significant differences were seen between the two groups for hematological analysis, weight or age. Ease of surgical handling was equivalent or superior to currently available technology. The PhotoFix valves had minimal leaflet calcification (mean 0.20 +/- 0.12 microg/mg) at 150 days. Two animals implanted with control valves were sacrificed at 173 and 227 days due to poor health; the control valves had massive thrombus and extensive leaflet mineralization (mean calcium content 18.2 +/- 3.8 microg/mg). For comparison with controls, two sheep with Photofix valves were sacrificed electively at 218 and 235 days. At 235 days, the experimental valve had a surgical suture looped over one commissure, restricting the motion of two leaflets and leading to massive inflow surface thrombosis. Despite this restriction, the animal remained healthy, with no noticeable regurgitation. The mean calcium content of the 218-day experimental valve leaflets was 6.28 microg/mg. Two experimental valves remain in place for long-term evaluation. CONCLUSION: In-vivo testing in juvenile sheep showed the PhotoFix pericardial valve to have no device-related mortality, no significant tissue degeneration, and minimal mineralization. In contrast, the control valves had significant valve mineralization and device-related morbidity.

Histology and morphology of 59 internal thoracic artery grafts and their distal anastomoses.

BACKGROUND: The left internal thoracic artery (LITA) is accepted as a superior graft for the left coronary system because of its better long-term patency rate than saphenous grafts. The postsurgical histomorphometric changes at the distal anastomosis of LITA grafts are not well documented. METHODS: The cellular changes within the intima of 59 LITA grafts were analyzed by light microscopy. RESULTS: Grafts implanted 1 week or less (n = 34) showed no postsurgical tissue proliferation. Of the 7 grafts implanted 1 to 8 weeks, only the suture sites exhibited intimal thickening (6 of 7 grafts, 0.08 +/- 0.07 mm). The remaining grafts (n = 18), aged 2 months to 10 years, showed significant intimal thickening at the suture sites (0.39 +/- 0.17 mm) and on the hood (0.29 +/- 0.25 mm), with variable thickening on the floor (10 of 18 left anterior descending coronary arteries, 0.11 +/- 0.12 mm). The graft body showed insignificant intimal changes (10 of 18, 0.03 +/- 0.04 mm), with mild focal atherosclerotic lesions in 2 of 18 late LITA grafts. CONCLUSIONS: Left internal thoracic artery grafts develop fibromuscular intimal hyperplasia primarily around the anastomosis. The response on the hood appears to be a hemodynamic response, secondary to that of the suture sites.

Cardiac angiosarcoma: two cases and a review of the literature.

BACKGROUND: Primary cardiac tumours are rare, and primary malignant cardiac tumours even rarer. Of these, cardiac angiosarcomas are uncommon and, until recently, almost invariably diagnosed at the time of autopsy, primarily because the symptoms are initially nonspecific and do not become manifest until the tumour is advanced. METHODS: Two patients, who presented in quite different manners and were diagnosed at autopsy and at open surgical biopsy, are presented. The literature on cardiac angiosarcomas is reviewed critically, with emphasis on presentation and morphology. RESULTS: This review of the literature shows that, with increasing availability of newer diagnostic tools, especially noninvasive ones, diagnosis of this rare lesion can be made at an early stage and confirmed at cardiac biopsy or cardiac surgery. Unfortunately, so far, the results remain virtually uniformly poor, though occasionally survival at up to 53 months has been reported.