A contemporary case series of lupus myocarditis.

OBJECTIVES: The purpose of this study was to describe clinical phenotype and treatment outcomes in lupus myocarditis (LM), an uncommon but serious manifestation of systemic lupus erythematosus (SLE). METHODS: The study involved a 10-year retrospective case series of hospitalized patients with LM, with a search of a diagnosis database using systemic lupus erythematosus and either myocarditis, cardiomyopathy, or congestive heart failure, and of a pathology database for biopsy-proved LM. RESULTS: Twenty-four patients met the study criteria, with 79% female and 82% white (age: mean (SD), 47.6 (20.4) years; follow-up: mean (SD), 9.2 (6.1) months). The frequency of antibodies SS-A (69%) and anti-RNP (62%) was greater than in published lupus populations (25%-40%). On echocardiography, the mean initial left ventricular ejection fraction was 33.8%, improving to 49.5% after a mean of 7.2 months. All patients received immunosuppression, most with high-dose corticosteroid treatment and subsequent corticosteroid taper. One patient died of cardiogenic shock during hospitalization; two patients died within one year posthospitalization. CONCLUSIONS: A high index of suspicion is necessary in suspected LM. Higher frequency of elevated SS-A and anti-RNP antibody levels in our series than in the literature is suggestive of an LM association. Echocardiography is a useful initial investigation for LM, but patients should be referred early for cardiac magnetic resonance imaging or endomyocardial biopsy to confirm diagnosis if it is clinically indicated in difficult cases.

Ebstein's anomaly - review of a multifaceted congenital cardiac condition.

Ebstein's anomaly (EA) is a rare but fascinating congenital heart disorder accounting for <1% of all congenital heart defects. Since its description in 1866, dramatic advances in diagnosis and therapy have been made. In this review, we describe current diagnostic criteria and classification, natural history, clinical features, and prognosis, typical echocardiographic features and pathologic findings, and the spectrum of associated cardiac malformations including left heart anomalies associated with EA. Differences between Ebstein-like changes associated with congenitally corrected transposition and EA are described. The spectrum of typical ECG and conduction system changes, arrhythmias including accessory pathways and ectopic atrial tachycardias related to EA are also reviewed. Differential diagnosis of EA is discussed including tricuspid valve dysplasia and prolapse as well as arrhythmogenic right ventricular cardiomyopathy. The review describes management options in EA including catheter interventions, indication for operation and surgical options including tricuspid valve repair and replacement. Overall, EA is a complex congenital anomaly with a broad pathologic-anatomical and clinical spectrum and no two patients are alike. Therefore, precise knowledge of the different anatomic and hemodynamic variables, associated malformations and management options are essential. Management of EA patients is complex. Thus it is important that these patients are regularly seen by a cardiologist with expertise in congenital heart disease.

Unguarded mitral orifice associated with discordant atrioventricular connection, double-outlet right ventricle, and pulmonary atresia.

We report a case of unguarded mitral valve orifice in a newborn boy that was associated with mirror-image cardiac sidedness, ambiguous abdominal sidedness, discordant atrioventricular connection, double-outlet right ventricle, and pulmonary atresia.

Estrogen status correlates with the calcium content of coronary atherosclerotic plaques in women.

BACKGROUND: Coronary artery calcium, a radiographic marker for atherosclerosis and a predictor of coronary heart disease (CHD), is less extensive in women than in men of the same age. The role of estrogen in the pathogenesis of coronary artery calcification is unknown. We examined the association of estrogen status with extent of calcification and atherosclerotic plaque in coronary arteries of deceased women. METHODS: Coronary arteries were obtained at autopsy from 56 white women age 18--98 yr, 46 postmenopausal and 10 premenopausal. Exclusion criteria included patients with coronary stents, coronary artery bypass surgery, and medical-legal cases. Medical records were reviewed for demographics, CHD risk factors, menstrual status, and use of estrogen replacement therapy. Contact microradiography of coronary arteries assessed true calcium content and atherosclerotic plaque area was analyzed histologically. RESULTS: The coronary arteries from estrogen-treated postmenopausal women had lower mean coronary calcium content (P = 0.002), mean plaque area (P < 0.0001), and calcium-to-plaque area ratio (P = 0.004) than those from untreated menopausal women. Estrogen status, age, diabetes, and hypertension predicted calcium and plaque area by univariate analysis. After controlling for these CHD risk factors, estrogen status remained an independent predictor of both calcium (P = 0.014) and plaque area (P = 0.001) in all women. Mean calcium area (P < 0.05) but not plaque area (P = 0.44) was significantly greater in women treated with estrogen replacement therapy than in premenopausal women. Coronary calcium (P < 0.007) and plaque area (P < 0.03) varied significantly with age in untreated postmenopausal women, but not in the estrogen-treated or premenopausal women (P = 0.33). CONCLUSIONS: Estrogen status is associated with coronary calcium and plaque area independent of age and CHD risk factors. Estrogen may modulate the calcium content of atherosclerotic plaques, as well as plaque area and may slow the progression of atherosclerosis in women.

Fulminant hepatic failure secondary to adenovirus following fludarabine-based chemotherapy for non-Hodgkin's lymphoma.

Self-limited adenoviral infections are very common with the majority of infections resolving rapidly. Fatal complications may occur in severely immunocompromised patients. We describe a case of fulminant hepatic failure due to adenovirus in a 54-year-old man treated with fludarabine and cyclophosphamide for non-Hodgkin's lymphoma. There are no previous reports of this complication in conjunction with purine nucleoside therapy.

Surgical pathology of the parietal pericardium: a study of 344 cases (1993-1999).

Among 344 cases with surgically resected parietal pericardium, ages ranged from 1 to 87 years (mean, 55), and 64% were male. Causes of pericardial disease included neoplastic (33%), idiopathic (30%), iatrogenic (23%), and others (14%). Pericardial constriction (Group 1) represented the largest group (143 cases, 76% male). Maximal pericardial thickness was 1-17 mm (mean, 4). Fibrotic thickening occurred in 96%. Chronic lymphoplasmacytic inflammation affected 73% (mild or moderate in 97%). Calcification was uncommon (gross in 28%, microscopic in 8%), and granulomas were rare (4%, none tubercular). Constriction was idiopathic in 49% and iatrogenic (postpericardiotomy or postirradiation) in 41%. Neoplasms and cysts (Group 2) represented the second largest group (96 cases). Among 43 cases with secondary pericardial involvement, carcinomas accounted for 53% and lymphomas 21%. Forty cases (Group 3) had pericardial effusions (75% chronic), which were idiopathic in 28% and postpericardiotomy in 23%. Thirty-three cases (Group 4) had acute or recurrent pericarditis clinically, which was idiopathic in 70%. Lastly, 32 cases (Group 5) had pericardial resection for conditions unrelated to primary pericardial disease. In conclusion, pericardial constriction tended to be nontubercular (100%), nongranulomatous (96%), idiopathic or iatrogenic (90%), and noncalcific (64%), and it could occur with normal pericardial thickness (4%). Because considerable overlap in the gross and microscopic features existed among cases with noncalcific pericardial constriction (Group 1), pericardial effusions (Group 3), and pericarditis (Group 4), clinical information was necessary to provide an accurate clinicopathologic interpretation.

Anatomy of the first septal perforating artery: a study with implications for ablation therapy for hypertrophic cardiomyopathy.

OBJECTIVE: To determine the variability in the size and distribution of the first septal perforating artery (FSPA). MATERIAL AND METHODS: In this pilot study, 10 fresh autopsy hearts from patients who did not have hypertrophic cardiomyopathy (HCM) or clinical evidence of coronary artery disease were evaluated for the variability in the size of the FSPA. The size of the FSPA was also measured during coronary angiography in 8 patients with HCM who were undergoing alcohol septal ablation. RESULTS: Of the 10 autopsy hearts, 2 had a large FSPA (> or = 1.0 mm in maximal diameter) with prominent septal myocardial distribution, 2 had a medium-sized FSPA (0.5-0.9 mm), 2 had a small FSPA (0.1-0.4 mm), 3 had a tiny FSPA (< 0.1 mm), and 1 had an indiscernible ostium. In 2 patients the FSPA supplied the right ventricular free wall. In 4 patients the basal ventricular septum was incompletely supplied by the FSPA. Of the 8 patients with HCM, the FSPA was larger than 2 mm in diameter in 2 patients, 1 to 2 mm in 4, and smaller than 1 mm in 2. The distance between the left anterior descending coronary artery ostium and the origin of the FSPA ranged between 13.1 and 37.4 mm, indicating a large variation in the size and distribution of the FSPA. CONCLUSIONS: Variability in the size and distribution of the FSPA in patients without HCM was substantial. Areas of the heart other than the basal septum were supplied in some patients by the FSPA. In other patients the FSPA did not supply the entire basal septum. Similar findings were noted in patients with HCM. A detailed evaluation of the distribution of the FSPA may be necessary in all patients with HCM who are undergoing alcohol septal ablation.

Experimental hypercholesterolemia induces apoptosis in the aortic valve.

BACKGROUND AND AIM OF THE STUDY: Aortic valve disease is presently the number one indication for valve replacement in the United States, yet its molecular mechanisms remain unknown. As apoptosis (programmed cell death) occurs in degenerative disease states, it was postulated that experimental hypercholesterolemia is associated with apoptosis in rabbit aortic valves. METHODS: New Zealand White rabbits (n = 8) were fed a 1% cholesterol diet for 12 weeks; control rabbits (n = 8) were fed a normal diet. After sacrifice of the animals, the aortic valves were dissected. Apoptosis was identified in the valvular lesion by TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique, and confirmed with transmission electron microscopy. The number of apoptotic cells was measured by computed morphometry. RESULTS: Valves from hypercholesterolemic rabbits showed an increase in apoptosis. TUNEL staining was identified in the atherosclerotic layer of hypercholesterolemic valves (0.1% of cells), but not in the cells of controls (p <0.0001). CONCLUSION: Apoptosis is increased in rabbit aortic valves during experimental hypercholesterolemia. If fatal cellular degeneration occurs in hypercholesterolemic valve disease, these data suggest that apoptosis may play a role in the mechanism of valvular disease.

Aortic aneurysms in children and young adults with tuberous sclerosis: report of two cases and review of the literature.

Abdominal aortic aneurysms (AAAs) in children and young adults are rare; some have been observed in patients with tuberous sclerosis (TS). We report two cases and review the literature. A 9-year-old girl with TS was diagnosed with a 3-cm calcified AAA, and a 41-year-old man with TS was diagnosed with a 7.5-cm thoracic aortic aneurysm (TAA). Both patients underwent open repair with a tube polyester graft without complication. They are both doing well at 7 and 8 years after surgery. Pathologic evaluation revealed medial atrophy and focal medial disruption in the aortic wall in both patients. With our two cases, 15 patients with TS and aneurysms have been reported; 12 had AAA, and four had TAA (one patient had both). Three AAAs and two TAAs ruptured. Six patients died because of aneurysmal disease. There is an association between TS and aortic aneurysms. Patients should be screened for aortic aneurysms at the time TS is diagnosed and annually thereafter. Because of the high risk of rupture, early elective repair is suggested. New aortic aneurysms after repair may also develop.

Reoperation for prosthetic aortic valve obstruction in the era of echocardiography: trends in diagnostic testing and comparison with surgical findings.

OBJECTIVES: We sought to: 1) identify trends in the diagnostic testing of patients with prosthetic aortic valve (AVR) obstruction who undergo reoperation and 2) compare diagnostic test results with pathologic findings at surgery. BACKGROUND: It is unclear whether Doppler transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have reduced hemodynamic catheterization rates. METHODS: We reviewed 92 consecutive cases ofAVR reoperation at a single center from 1989 to 1998, comparing 49 cases of mechanical AVR obstruction (group A) to 43 cases of bioprosthetic obstruction (group B). Preoperative Doppler TTE was performed in all cases. RESULTS: In group A cases, there was a marginally significant trend towards lower catheterization rates for the Gorlin AVR area, from 36% in 1989 to 1990 to 10% in 1997 to 1998 (p = 0.07), but diagnostic TEE utilization (47% of cases) did not vary. The cause of mechanical AVR obstruction was pannus in 26 cases (53%), mismatch (P-PM) in 19 (39%) and thrombosis in 4 (8%). The mechanism (pannus/thrombus vs. mismatch) was identified in 10% by TTE and 49% by TEE (p < 0.001). In group B cases, hemodynamic catheterization rates (21%) and diagnostic TEE utilization (21%) did not vary with time. Obstruction was caused by structural degeneration in 37 cases (86%), thrombosis in 3 (7%), mismatch in 2 (5%) and pannus in 1 (2%). The mechanism was correctly identified in 63% by TTE and in 81% by TEE (p = 0.18). CONCLUSIONS: Doppler TTE is the primary means to diagnose AVR obstruction; hemodynamic catheterization is not routinely needed. In unselected patients with mechanical AVR obstruction, TEE differentiation of pannus or thrombus from mismatch is challenging.

Outcome of reoperation for aortic valve prosthesis-patient mismatch.

We report a single center's 10-year experience with 21 consecutive cases of repeat aortic valve replacement for prosthesis-patient mismatch (P-PM) in which there was no hospital mortality among 12 patients treated for isolated P-PM. With an overall survival of 92% at a median follow-up of 4.5 years and functional class I symptoms in most survivors (73%), we conclude that repeat surgery for isolated P-PM has a relatively low mortality and a good intermediate-term clinical outcome.

Cell proliferation in carcinoid valve disease: a mechanism for serotonin effects.

BACKGROUND AND AIM OF THE STUDY: Elevated serum serotonin is associated with carcinoid heart disease, the hallmark of which is valvular thickening. Yet, the mechanistic role of serotonin in carcinoid heart disease is poorly understood. We postulated that serotonin has a direct mitogenic effect on cardiac valvular subendocardial cells, and that this effect is mediated by serotonin receptors. METHODS: The dose-dependent proliferative effects of serotonin (10(-8) to 10(-4)M) on cultured porcine aortic valve cells via a [3H]thymidine assay were determined in vitro. Serotonin receptor antagonist studies in culture were also performed using methiotepin, a 5HT1b antagonist, and ketanserin, a 5HT2 receptor antagonist, to determine the mechanism of serotonin action. The ex-vivo proliferation level in human carcinoid (n = 26) and normal valves (n = 10) was compared using proliferating cell nuclear antigen (PCNA) staining, a marker for proliferation. Identification and localization of specific 5HT receptor was assessed by immunostaining for serotonin receptors in the valves. RESULTS: Serotonin increased valvular proliferation in vitro in a dose-dependent manner (10-fold increase) (p <0.001), and this mitogenic effect was inhibited by methiotepin but not ketanserin. In human carcinoid heart valves the level of proliferation was 35-fold higher than in normal human valves (p <0.001). 5HT1b receptors were found only in the carcinoid valves, and not in the normal valves. CONCLUSION: Serotonin is a powerful mitogen for valvular subendocardial cells. The mitogenic effect is at least partly mediated via 5HT1b receptors. Subendothelial cell proliferation is significantly elevated in human carcinoid valves in vivo. The data suggest a mechanism whereby serotonin may contribute to valvular proliferation in carcinoid heart disease.

Asymptomatic giant right atrial aneurysm.

A 5-year-old asymptomatic boy was found incidentally, on a chest radiograph, to have gross cardiomegaly; further evaluation by echocardiography showed a giant right atrial aneurysm. The patient underwent successful surgical reduction of the right atrium, closure of an atrial septal defect, and tricuspid valve repair These measures were taken to prevent thrombus formation in the right atrium, prevent paradoxical embolism, and lower the risk of atrial arrhythmias. The morphologic features of the resected atrial tissue showed paper-thin wall with a central aneurysm and focal endocardial fibrosis consistent with a diagnosis of idiopathic dilatation of the right atrium.

Surgical pathology of nonbacterial thrombotic endocarditis in 30 patients, 1985-2000.

OBJECTIVE: To describe the causes, complications, and histological appearance of nonbacterial thrombotic endocarditis (NBTE) in a surgical population compared with those in previously reported autopsy series. PATIENTS AND METHODS: Cases were identified by reviewing the surgical pathology reports for all cardiac valvular specimens removed at Mayo Clinic, Rochester, Minn., between 1985 and 2000. Archived microscopic slides and medical records were reviewed for each study patient. RESULTS: The study group consisted of 30 patients (20 female and 10 male), with a mean age of 49 years (range, 15-89 years). Of these 30 patients, 28 had single valve involvement (19 mitral, 8 aortic, and 1 tricuspid), and 2 had involvement of both their mitral and aortic valves. An underlying immune-mediated disorder was identified in 18 patients (60%), including primary antiphospholipid syndrome (in 8), rheumatic heart disease (in 6), systemic lupus erythematosus (in 2), and rheumatoid arthritis (in 2), 15 (83%) of whom were women. Of the remaining 12 patients with no autoimmune disease, only 5 (42%) were women. No patient had metastatic malignant disease or disseminated intravascular coagulopathy. Systemic embolization was documented in 10 patients (33%), 8 of whom had cerebral involvement. Valvular vegetations were visualized by echocardiography before surgery in 8 patients and were suspected but not confirmed preoperatively in 1 patient. All vegetations consisted primarily of platelets and fibrin. The site and appearance of vegetations did not vary with the underlying disease state. CONCLUSIONS: In contrast to previously reported autopsy series, NBTE in a surgical population was more commonly associated with autoimmune disorders than malignancy or disseminated intravascular coagulopathy. Women were affected twice as often as men. Systemic embolization, particularly to the brain, was prominent in both surgical and autopsy series. Vegetations had a similar appearance regardless of the specific underlying disease. An antemortem diagnosis of NBTE in a patient with no known risk factors should prompt a search not only for occult malignancy, as suggested by autopsy studies, but also for autoimmune or rheumatic diseases, particularly the antiphospholipid syndrome.

Death from inappropriate therapy for Lyme disease.

A 30-year-old woman died as a result of a large Candida parapsilosis septic thrombus located on the tip of a Groshong catheter. The catheter had been in place for 28 months for administration of a 27 month course of intravenous cefotaxime for an unsubstantiated diagnosis of chronic Lyme disease.

Antiphospholipid syndrome and perioperative hemostatic management of cardiac valvular surgery.

Hemostatic aspects of antiphospholipid syndrome (APS) present unique challenges to clinicians and laboratory personnel alike, particularly in the perioperative period. These challenges are especially evident in patients requiring cardiac valve replacement surgery. However, the literature outlining the optimal approach in such patients is limited. We present the case of a 25-year-old woman with severe aortic regurgitation as a result of APS with particular reference to the precautions necessary during perioperative care. Particularly important are the prevention of thrombotic or hemorrhagic complications, management of associated thrombocytopenia, and laboratory methods of perioperative anticoagulation monitoring in the setting of prolonged clotting times.

Right ventricular infarction associated with anteroseptal myocardial infarction: a clinicopathologic study of nine cases.

The association of right ventricular (RV) infarction with inferoseptal myocardial infarction is well established. However, a question remains about the occurrence of RV infarction in association with anteroseptal myocardial infarction. To determine the frequency and clinical correlates of this entity, we studied autopsied hearts from patients with isolated anteroseptal left ventricular (LV) infarcts. Among 3,249 autopsy specimens, 88 cases were identified. From each, sections were taken from the RV anterior, lateral, and inferior regions at basal, middle, and apical levels. All 1,584 slides were reviewed by blinded assessment. RV and LV infarcts were compared to confirm similarity in age. Patient records and cardiac investigations were reviewed for evidence of RV involvement. Of the 88 hearts with anteroseptal LV infarcts, 9 (10%) had coexistent RV infarction (6, old; 3, new). For these 9, the RV infarction involved 11% to 33% of the RV area, and the left anterior descending coronary artery was the infarct-related artery in each. All 3 patients who had an echocardiographic examination within 4 weeks of anteroseptal LV infarction had RV dysfunction. One patient, studied 15 years after infarction, had a normal right ventricle by echocardiography. In 3 patients with acute myocardial infarction, right heart catheterization during the acute phase revealed increased right-sided diastolic pressures out of proportion to left-sided diastolic pressures (right atrial pressure to pulmonary capillary wedge pressure, 60% to 95%). In conclusion, 10% of patients with an isolated anteroseptal LV infarct had evidence of RV free wall infarction. The RV infarction was associated with identifiable hemodynamic and echocardiographic features.

Symptomatic ischemic heart disease resulting from obstructive intramural coronary amyloidosis.

PURPOSE: Obstructive intramural coronary amyloidosis is an unusual complication of systemic amyloidosis. SUBJECTS AND METHODS: We review the characteristics of 11 patients seen at the Mayo Clinic (Rochester, Minnesota) from January 1, 1960, to June 1, 1999, with intramural cardiac amyloidosis diagnosed at autopsy or after examination of an explanted heart. RESULTS: Symptomatic ischemic heart disease resulting from obstructive intramural coronary amyloidosis was found in 11 patients (8 men, 3 women). The mean (+/-SD) age at the diagnosis of primary amyloidosis was 62 +/- 12 years. All patients had angina pectoris; angina was the presenting symptom of primary amyloidosis in 6 patients. Unstable coronary syndromes occurred in 7 patients and congestive heart failure in 8. New electrocardiographic abnormalities after the development of angina were common and included ischemic changes, bundle branch block, and dysrhythmias. Low voltage was seen in only 2 patients. All 7 patients who underwent coronary angiography had normal or clinically insignificant findings. Endomyocardial biopsy was performed on 4 patients; amyloid was found in 3 patients, none of whom had obstructive intramural coronary amyloidosis. The diagnosis of obstructive intramural coronary amyloidosis with associated myocardial injury was established only at autopsy or after examination of the explanted heart after cardiac transplantation. The mean time to death or cardiac transplantation after symptoms of cardiac ischemia developed was 18 +/- 20 months. CONCLUSIONS: The diagnosis of ischemic heart disease resulting from obstructive intramural coronary amyloidosis is difficult to establish before death or cardiac transplantation. Although the condition has a poor prognosis, its accurate recognition may have therapeutic implications, because some patients may benefit from treatment, including systemic chemotherapy or cardiac transplantation.

Graves' disease and low-output cardiac dysfunction: implications for autoimmune disease in endomyocardial biopsy tissue from eleven patients.

Classic high-output thyrotoxic heart disease is generally considered a direct effect of thyroid hormone. In contrast, the cause of the less common low-output heart failure is generally unknown. The aim of this study was to retrospectively evaluate available endomyocardial biopsy tissue from patients with coexistent Graves' disease and idiopathic low-output heart failure and determine whether the biopsy features were consistent with an autoimmune process. The study group consisted of 11 patients whose mean age was 47 years when they were diagnosed with hyperthyroidism and 52 years when diagnosed with cardiac dysfunction. Right ventricular endomyocardial biopsy tissue revealed severe lymphocytic myocarditis in a patient with severe ophthalmopathy and showed borderline myocarditis in a patient without ophthalmopathy. Biopsy tissues from 6 other patients showed appreciable myocyte hypertrophy and interstitial fibrosis, consistent with dilated cardiomyopathy. Two patients had nondiagnostic biopsy specimens, and 1 patient had features suggestive of arrhythmogenic right ventricular dysplasia. In conclusion, for the 11 patients with Graves' disease and unexplained systolic dysfunction, only 2 (18%) had lymphocytic infiltrates consistent with an autoimmune process. Thus, among patients with Graves' disease, most cases of low-output cardiac dysfunction appear to be due to causes other than an active autoimmune inflammatory process.