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Biomedical subjects

William D Edwards

Publications and source records attributed to William D Edwards.

At least 37 records · Page 2Linked to original sources
PubMed2005

Sudden unexpected death in a 31-year-old man caused by arrhythmogenic right ventricular cardiomyopathy.

A 31-year-old white man collapsed suddenly at a graduation ceremony and was pronounced dead after attempted resuscitation. He had no pertinent medical or familial history. Postmortem toxicologic studies showed negative results. A complete autopsy revealed a cardiac cause of death. Grossly, the right ventricular chamber was moderately to markedly dilated, and its free wall showed extensive myocardial adiposity. Microscopically, the right ventricular free wall consisted predominantly of adipose tissue, with only small subendocardial islands of hypertrophied myocytes and interstitial fibrosis. These features are characteristic of arrhythmogenic right ventricular cardiomyopathy. Moreover, Purkinje-like cells were observed among right ventricular myocytes and may have increased the likelihood of developing an arrhythmia. To our knowledge, this finding has not been previously emphasized. Because arrhythmogenic right ventricular cardiomyopathy accounts for 10% of cases of sudden unexpected cardiac death, recognition of this disease by pathologists is important, especially in cases of otherwise unexplained death in young persons.

Adult↗
PubMed2004

Alcohol septal ablation versus surgical septal myectomy: comparison of effects on atrioventricular conduction tissue.

OBJECTIVES: This study was designed to evaluate the effect of septal reduction therapies on the conduction system for patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Heart block is a potential complication of both catheter-based and surgical procedures to relieve left ventricular outflow tract obstruction in HCM, but it is important to understand the different effects of these treatments on the conduction system. METHODS: The electrocardiograms and postoperative course of patients who underwent percutaneous alcohol septal ablation or surgical myectomy at Mayo Clinic between 1999 and 2003 were reviewed. RESULTS: For the 58 patients who underwent alcohol septal ablation, 21 (36%) developed right bundle branch block. Six patients (12%) developed complete heart block requiring permanent pacing, three of whom had left bundle branch block before the procedure. Among the 117 patients who underwent surgical septal myectomy, 47 (40%) developed left bundle branch block. Four patients (3%) developed heart block requiring permanent pacing after the procedure, three of whom had right bundle branch block preoperatively. CONCLUSIONS: Percutaneous septal ablation selectively produces transmural infarction of the basal mid-septum and adjacent right bundle tissue, whereas surgical myectomy affects the endocardial portion of the basal anterior septum and adjacent left bundle tissue. These observations may help identify patients at risk for complete heart block after septal reduction procedures for HCM.

Atrioventricular Node↗
PubMed2004

Acute and chronic reduction of functional mitral regurgitation in experimental heart failure by percutaneous mitral annuloplasty.

OBJECTIVES: We sought to determine acute and chronic efficacy of a percutaneous mitral annuloplasty (PMA) device in experimental heart failure (HF). Further, we evaluated the potential for adverse effects on left ventricular (LV) function and coronary perfusion. BACKGROUND: Reduction of mitral annular dimension with a PMA device in the coronary sinus may reduce functional mitral regurgitation (MR) in advanced HF. METHODS: Study 1: a PMA device was placed acutely in anesthetized open-chest dogs with rapid pacing-induced HF (n = 6) instrumented for pressure volume analysis. Study 2: in 12 anesthetized dogs with HF, fluoroscopic-guided PMA was performed, and dogs were followed for four weeks with continuing rapid pacing. RESULTS: Study 1: percutaneous mitral annuloplasty reduced annular dimension and severity of MR at baseline and with phenylephrine infusion to increase afterload (MR jet/left atrial [LA] area 26 +/- 1% to 7 +/- 2%, p < 0.05). Pressure volume analysis demonstrated no acute impairment of LV function. Study 2: no device was placed in two dogs because of prototype size limitations. Attempted PMA impaired coronary flow in three dogs. Percutaneous mitral annuloplasty (n = 7) acutely reduced MR (MR jet/LA area 43 +/- 4% to 8 +/- 5%, p < 0.0001), regurgitant volume (14.7 +/- 2.1 ml to 3.1 +/- 0.5 ml, p < 0.05), effective regurgitant orifice area (0.130 +/- 0.010 cm(2) to 0.040 +/- 0.003 cm(2), p < 0.05), and angiographic MR grade (2.8 +/- 0.3 device to 1.0 +/- 0.3 device, p < 0.001). In the conscious state, MR was reduced at four weeks after PMA (MR jet/LA area 33 +/- 3% HF baseline vs. 11 +/- 4% four weeks after device, p < 0.05) CONCLUSIONS: Percutaneous mitral annuloplasty results in acute and chronic reduction of functional MR in experimental HF.

Animals↗
PubMed2004

Global remodeling of the ventricular interstitium in idiopathic myocardial fibrosis and sudden cardiac death.

OBJECTIVE: Characterization of a distinct, and as yet unexplained phenotype of sudden cardiac death (SCD). BACKGROUND: In a subgroup of patients with SCD, postmortem findings are limited to isolated idiopathic myocardial fibrosis (IMF). The absence of confounding factors may facilitate evaluation of the relationship between myocardial fibrosis and ventricular arrhythmogenesis. METHODS: Six patients with IMF were identified from a postmortem, consecutive 13-year series of 270 subjects presenting with SCD. Ventricular interstitial remodeling was assessed quantitatively and qualitatively and comparisons made with 6 age- and sex-matched control subjects who suffered noncardiac death. Myocardial collagen volume fraction and perivascular fibrosis ratio were determined and evidence for inflammatory response and apoptotic cell death was sought. The potential role of transforming growth factor beta 1 (TGF-beta(1)) in the pathogenesis of IMF was evaluated. RESULTS: Overall myocardial collagen volume fraction was 1.6-fold higher in IMF (mean age 34 +/- 4 yrs) vs. controls (mean age 34 +/- 4 yrs, .022 +/- .001 vs .013 +/- .001; P < .001). Collagen volume fraction increase was diffuse but disproportionately so in the LV inferior wall (3.4-fold increase; .035 +/- .005 vs .012 +/- .018; P < .001). Perivascular fibrosis ratio was also increased (.770 +/- .014 vs .723 +/- .010; P = .007). There was no evidence of either myocardial inflammatory response or myocyte apoptosis in cases or controls. Expression of TGF-beta(1) was significantly increased in IMF vs controls. CONCLUSION: IMF involves diffuse and heterogeneous remodeling of the ventricular interstitium, with a predilection for the LV inferior wall. TGF-beta(1) is a potential mediator of interstitial remodeling in IMF and SCD.

Adult↗
PubMed2004

Surgical pathology of infected aneurysms of the descending thoracic and abdominal aorta: clinicopathologic correlations in 29 cases (1976 to 1999).

Infected aortic aneurysms are uncommon, and only rarely have their surgical pathological features been described. Clinical and histopathologic features were evaluated in patients undergoing surgical repair of infected aneurysms of the descending thoracic or abdominal aorta over a 24-year period. Findings were compared with observations (primarily from autopsy studies) from the previous 25-year period (1950 to 1975) and other more recent reports. Of the 29 patients in our study, 79% were men, 90% had risk factors for atherosclerosis, and 72% had an identifiable risk or source of infection. Fever was present in 76%, and abdominal or back pain was seen in 66%. Among the 20 cases with an identifiable causative organism, staphylococcus accounted for 30%, streptococcus for 20%, salmonella for 20%, Escherichia coli for 15%, and other organisms for 15%. Aneurysms were saccular in 59% and infrarenal in 42%, and had a mean diameter of 5.6 cm. Microscopically, 6 patterns were recognized: acute inflammation superimposed on severe chronic atherosclerosis (55%), atherosclerosis with chronic inflammation (20%), acute inflammation without atherosclerosis (7%), chronic adventitial inflammation (7%), pseudoaneurysm formation (7%), and necrotizing granulomatous inflammation (4%). Special stains for organisms were positive in only 38% of the cases. Pathological findings of this series of surgical specimens spanning the fourth quarter of the twentieth century were not appreciably different from those described in autopsy series from the preceding years, although the causative microorganisms and agents used to treat them, preoperative diagnostic modalities, and surgical approaches have evolved.

Aged↗
PubMed2004

Fatal coronary artery disease after unrelated donor bone marrow transplantation.

Several factors are responsible for the occurrence of cardiac complications after bone marrow transplantation (BMT). These factors include the cardiotoxic effects of radiation therapy, antineoplastic and immunosuppressive drugs, abnormal immunologic reactions associated with graft-vs-host disease, and infectious agents. We report the case of a 45-year-old woman with T-cell prolymphocytic leukemia and no prior risk factors for coronary artery disease in whom sudden cardiac death occurred 2 1/2 years after allogeneic BMT from an unrelated male donor. Autopsy revealed severe 3-vessel coronary disease with grade 4/4 stenosis. This process was primarily nonatherosclerotic, with intimal hyperplasia of undetermined etiology. Furthermore, fluorescence in situ hybridization to identify the donor Y chromosome with simultaneous immunofluorescence labeling of smooth muscle actin suggested the presence of donor cells that transformed into myocytes. Coronary artery disease is an important, albeit rare, complication of BMT. Donor hematopoietic cells may contribute to its pathogenesis.

Bone Marrow Transplantation↗
PubMed2004

Heart and liver disease in 32 patients undergoing biopsy of both organs, with implications for heart or liver transplantation.

OBJECTIVE: To determine underlying conditions in patients undergoing both heart and liver biopsies. PATIENTS AND METHODS: Our study group consisted of 32 patients at the Mayo Clinic in Rochester, Minn, who underwent both endomyocardial and nonsurgical liver biopsies and who underwent at least one of these procedures between January 1,1981, and December 31,2000. Patients were categorized as having (1) heart disease affecting the liver, (2) liver disease affecting the heart, (3) the same disease affecting both organs, or (4) different diseases affecting each organ independently. RESULTS: Among 32 patients, cardiac dysfunction was present in 28 (19 systolic, 9 diastolic), and hepatic dysfunction was present in 31. In group 1, 3 of 4 patients had cardiac amyloidosis with secondary hepatic congestion. In group 2, all 3 patients had cirrhosis with cirrhotic cardiomyopathy. Group 3 included 5 patients with hemochromatosis, 3 with alcoholism, and 1 with amyloidosis. In group 4, 8 of 16 patients had idiopathic cardiomyopathy, and 8 had hepatitis. Overall, of 8 patients with hemochromatosis, 3 without cardiac iron had improved cardiac function after phlebotomy, and 1 with cardiac iron had no cardiac dysfunction. Among 7 patients with alcoholism, 3 had alcoholic liver and heart disease. Of 5 patients with cardiac amyloidosis, 1 had hepatic amyloid. Ten patients underwent transplantation (6 liver, 3 heart, and 1 heart and liver). CONCLUSIONS: In one half of the patients in the study group, heart and liver diseases had independent causes. In patients with hemochromatosis, there was little correlation between cardiac iron and systolic dysfunction. In patients with chronic alcoholism, liver and heart disorders often had nonalcoholic causes. With cardiac amyloidosis, hepatic dysfunction was generally due to congestion. Specific disease in one organ did not necessarily imply similar involvement in the other. Thus, heart or liver biopsy may be useful in patients being evaluated for liver or heart transplantation, respectively.

Adolescent↗
PubMed2004

Aspergillus infection of implantable cardioverter-defibrillator.

The use of pacemakers and implantable cardioverter-defibrillators continues to increase for the management of cardiac dysrhythmias and, more recently, heart failure. Long-term complications associated with their use include infection, lead failure, and spurious shocks. Although the risk of infection with intracardiac devices is well known, the clinical presentation of this complication can be insidious, delayed in onset, and difficult to diagnose. We report a case of Aspergillus fumigatus infection of an implantable cardioverter-defibrillator with right-sided endocarditis in a 55-year-old man. The infection presented as persistent pulmonary infiltrates (due to recurrent septic pulmonary embolism) and anemia more than 2 years after implantation of the device. Clinicians should be aware of the variable manifestations resulting from infection of intracardiac devices.

Amphotericin B↗
PubMed2003

Eosinophilic-lymphocytic myocarditis after smallpox vaccination.

Smallpox is an eradicated viral disease that has re-emerged as a potential bioterrorism threat. Smallpox vaccination was historically the most effective defence measure against wild smallpox virus. The risk of myopericarditis after vaccination might limit this option. We report a case of biopsy-proven eosinophilic-lymphocytic myocarditis diagnosed in vivo with histological evidence for eosinophil-mediated cardiac myocyte necrosis shortly after smallpox vaccination. Furthermore, we report a beneficial haemodynamic response to high-dose corticosteroids. A better understanding of the aberrant immune mechanism of myocyte injury after smallpox vaccination might improve the risk/benefit assessment for people considering smallpox vaccination and better smallpox vaccines in the future.

Adult↗
PubMed2003

Constrictive pericarditis in 26 patients with histologically normal pericardial thickness.

BACKGROUND: Traditionally, increased pericardial thickness has been considered an essential diagnostic feature of constrictive pericarditis. Although constriction with a normal-thickness pericardium has been demonstrated clinically by noninvasive imaging, the details of clinicopathological correlates have not been described. METHODS AND RESULTS: A total of 143 patients with proven constriction underwent pericardiectomy at Mayo Clinic between 1993 and 1999. Their baseline characteristics, operative data, and pathological specimens were reviewed retrospectively. The pericardium was of normal thickness (< or =2 mm) in 26 patients (18%; group 1) and was thickened (>2 mm) in 117 (82%; group 2). The most common causes of constriction in group 1 included previous cardiac surgery, chest irradiation, previous infarction, and idiopathic disease. There was little difference in symptoms and findings on physical examination between the 2 groups. Microscopically, no patient had an entirely normal pericardium. Histopathological abnormalities in group 1 were mild and focal, including fibrosis, inflammation, calcification, fibrin deposition, and focal noncaseating granulomas. Pericardiectomy was equally effective in relieving symptoms regardless of the presence or absence of increased thickness. CONCLUSIONS: Pericardial thickness was not increased in 18% of patients with surgically proven constrictive pericarditis, although the histopathological appearance was focally abnormal in all cases. When clinical, echocardiographic, or invasive hemodynamic features indicate constriction in patients with heart failure, pericardiectomy should not be denied on the basis of normal thickness as demonstrated by noninvasive imaging.

Adult↗
PubMed2003

Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation.

Atherosclerosis is the major cause of adult mortality in the developed world, and a significant contributor to atherosclerotic plaque progression involves smooth muscle cell recruitment to the intima of the vessel wall. Controversy currently exists on the exact origin of these recruited cells. Here we use sex-mismatched bone marrow transplant subjects to show that smooth muscle cells throughout the atherosclerotic vessel wall can derive from donor bone marrow. We demonstrate extensive recruitment of these cells in diseased compared with undiseased segments and exclude cell-cell fusion events as a cause for this enrichment. These data have broad implications for our understanding of the cellular components of human atherosclerotic plaque and provide a potentially novel target for future diagnostic and therapeutic strategies.

Adult↗
PubMed2003

Left atrial isomerism: clinicopathologic findings in a 14-year-old boy.

Visceral heterotaxy syndromes have been associated with complex congenital heart disease and several attempts have been made to classify these lesions. One area of controversy that remains is the existence of atrial isomerism. In this case report we provide definite anatomic evidence of the existence of left atrial isomerism, wherein both the atria have smooth walls, finger-like appendages, and absence of the pectinate muscles and sinus node.

Adolescent↗
PubMed2003

Surgical pathology of pulmonary thromboendarterectomy: a study of 54 cases from 1990 to 2001.

Thromboendarterectomy is performed to treat chronic thromboembolic pulmonary hypertension with obstruction of main, lobar, or segmental pulmonary arteries. The present study evaluated surgical specimens removed between 1990 and 2001. Medical histories and microscopic slides were reviewed in each case. Study slides were stained with hematoxylin and eosin and Verhoeff-van Gieson and evaluated for thrombus, collagen, elastin, atherosclerosis, hemosiderin, calcification, and inflammation. The study group comprised 54 patients (30 women and 24 men), ranging in age from 33 to 77 years (mean, 58 years). Clinically, 28 (52%) had a history of deep leg vein thrombosis and 42 (78%) had a history of pulmonary embolism; 24 (44%) had both events. Coagulation abnormalities were documented in 15 (28%); autoimmune or hematologic disorders, in 8 (15%). Pulmonary thromboendarterectomy was bilateral in 52 patients (96%) and right-sided in 2. Six patients also had obstructions resected from the main pulmonary arteries. Obstruction limited to segmental arteries occurred only in women. Grossly, right-sided specimens were larger than left-sided ones (P = 0.003). Microscopically, ages of thrombi were uniform in 72% and variable in 28%. Intima was thickened in all patients and consisted of collagen (100%), elastin (67%), hemosiderin (56%), inflammation (53%), atherosclerosis (32%), and calcification (15%). We determined that pulmonary thromboendarterectomy was performed most often in middle-aged and elderly patients with a history of deep venous thrombosis or pulmonary embolism. Less than 50% of the patients had an identifiable coagulation, autoimmune, or hematologic abnormality. Most patients had bilateral disease and resections. Right-sided specimens were significantly larger than left-sided specimens, and lower lobe involvement was more common than involvement elsewhere. Resected tissues most commonly exhibited old organized thrombus.

Adult↗
PubMed2003

Mechanical prosthetic valve-associated strands: Pathologic correlates to transesophageal echocardiography.

Echocardiographic detection of prosthetic valve-associated strands has previously been reported, but their clinical relevance is unclear. Limited data are available regarding the cause, composition, and natural history of these strands. This report presents the gross and histopathologic findings of an explanted mechanical prosthetic valve shown by transesophageal echocardiography to have several strands. The patient had not experienced prior neurologic symptoms. Potential causes of strand formation in various clinical settings are also discussed.

Aged↗
PubMed2002

Increased ubiquitin immunoreactivity in unstable atherosclerotic plaques associated with acute coronary syndromes.

OBJECTIVES: The current study was designed to examine whether ubiquitin expression is higher in unstable than in stable lesions of patients with acute coronary syndrome (ACS). BACKGROUND: The ubiquitin system has been identified as the nonlysosomal pathway of protein degradation; it is involved in a number of biologic processes crucial to cell and tissue integrity and therefore, might be potentially involved in the rupture of unstable coronary plaques. METHODS: We conducted an autopsy-based study of 25 consecutive patients with fatal ACS. Lesions of both infarct-related and noninfarct-related segments from the same patients were examined for the expression and localization of ubiquitin by use of immunohistochemistry and a semiquantitative grading scale. RESULTS: Ubiquitin immunoreactivity was higher in infarct-related than in noninfarct-related lesions (1.4 +/- 0.5 vs. 1.1 +/- 0.6, p = 0.03). Compared with areas adjacent to the plaque (0.6 +/- 0.7), ubiquitin immunoreactivity was higher in areas around the lipid core (2.5 +/- 0.8, p < 0.001), plaque shoulders (1.6 +/- 1.1, p < 0.001), and fibrous cap regions (1.6 +/- 1.1, p < 0.001). Within the plaque area, co-localization of ubiquitin immunoreactivity with T cells and macrophages was found. In areas adjacent to the plaque, ubiquitin immunoreactivity co-localized with neointima cells and media smooth muscle cells. CONCLUSIONS: In patients with ACS, ubiquitin immunoreactivity is enhanced in unstable, infarct-related lesions, predominantly in plaque regions of tissue degradation. Based on these findings, this study suggests a role for the ubiquitin system in the destabilization and rupture of coronary atherosclerotic plaques in humans.

Acute Disease↗
PubMed2002

Metastatic carcinoid tumor to the heart: echocardiographic-pathologic study of 11 patients.

OBJECTIVE: We sought to investigate the clinical and echocardiographic (echo) characteristics of metastatic carcinoid tumor in the heart. BACKGROUND: Right-sided valvular dysfunction is the hallmark of carcinoid heart disease. Cardiac metastases are uncommon in carcinoid syndrome. Features of patients with metastatic carcinoid tumor involving the heart (MCH) have not been well described. METHODS: From 1985 through 1999, 11 patients (8 male, 3 female), mean age +/- standard deviation, 58 +/- 6 years, were seen who had pathologically confirmed MCH. All patients had echoes, which were reviewed retrospectively. RESULTS: All patients with MCH had carcinoid syndrome. The primary carcinoid tumor was in the small bowel in 83% of patients, and all patients had hepatic metastases. On pathologic review, the 11 patients had 15 MCH tumors. All metastases were intramyocardial. The MCH involved the right ventricle in 40%, left ventricle in 53%, and ventricular septum in 7%. The average size of macroscopic tumors was 1.8 +/- 1.2 cm. Nine MCH tumors were detected by echo in 6 of the 11 patients (55%). Mean echo-detected tumor size was 2.4 cm (range, 1.2 to 4). All tumors noted by echo were well circumscribed, non-infiltrating, and homogeneous. In the 5 other patients, review of autopsy records revealed 6 macroscopic tumors, mean size 0.35 cm (range, 0.2 to 0.4), none detected by echo even retrospectively. Carcinoid valve disease was present in 8 of the 11 MCH patients. The tricuspid valve was affected in all 8 patients (73%), pulmonary valve in 7 (64%), and left sided valves in 4 (36%) All patients with MCH identified by echo had cardiac surgery, 3 primarily for carcinoid valve disease and 2 for non-carcinoid cardiac disease; in 1 patient, MCH was the primary indication for cardiac surgery. CONCLUSIONS: MCH is uncommon but can be easily identified by echo if tumor size is >/=1.0 cm. In patients without valvular dysfunction, MCH may be the only manifestation of carcinoid heart disease. A search for MCH should be an integral part of the echo exam in patients with carcinoid syndrome.

Age of Onset↗
PubMed2002

Nuclear factor-kappaB immunoreactivity is present in human coronary plaque and enhanced in patients with unstable angina pectoris.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a transcription factor which plays a coordinating role in inflammation and cellular proliferation and is thought to be involved in the pathogenesis of atherosclerosis. Its role in unstable coronary plaque in humans is unknown. METHODS AND RESULTS: Coronary atherectomy plaque was obtained via directional coronary atherectomy from 32 patients [16 with unstable angina pectoris (UAP) and 16 with stable angina pectoris (SAP)]. The predominant pathology in UAP consisted of richly cellular areas with atheromatous gruel or loose intimal proliferative tissue within a myxoid matrix (P<0.05 compared with SAP). By contrast, SAP plaques showed more dense fibrosis (P<0.01 compared with UAP). Sections were then stained with a monoclonal antibody to the activated p65 subunit of NF-kappaB and this staining was present in 31/32 specimens, localized to smooth muscle cells, macrophages and foam cells. Staining was then graded semiquantitatively by three independent observers. Immunostaining grades for activated NF-kappaB were significantly higher in UAP compared with SAP (2.60+/-0.1 vs. 1.98+/-0.18; P<0.01). CONCLUSIONS: NF-kappaB immunoreactivity is present in coronary atherosclerotic plaque and is increased among patients with unstable coronary syndromes. These data support a role for NF-kappaB in the pathogenesis of acute coronary syndromes in humans.

Adult↗