Faculty Bibliography

Primary tumors of the aorta are rare entities. We report the unusual manifestation of an aortic intimal sarcoma that presented as a brain metastasis in a 56-year-old, otherwise healthy woman. After the brain mass had been resected, multiple imaging methods revealed pseudocoarctation and the primary tumor in the aortic arch. To our knowledge, this is the first report of the diagnosis of an aortic intimal sarcoma with use of real-time, 3-dimensional transesophageal echocardiography.

Aortocava fistula is a rare condition ranging from 0.22% to 6% of all ruptured aortic aneurysms. Recognition and diagnosis of this entity can often be difficult and requires heightened clinical suspicion to ensure that prompt surgical management leads to a favorable outcome. We herein describe the diagnosis and the technical points of successful endovascular management of aortocaval fistula in the setting of a ruptured abdominal aortic aneurysm.

Primary cardiac synovial sarcoma is a rare malignancy, comprising approximately 5% of cardiac sarcomas and fewer than 0.1% of all primary cardiac tumors. Synovial sarcoma is typically characterized by a t(X;18)(p11.2;q11.2) translocation resulting in fusion of the SS18 (aka SYT) gene on chromosome 18 with the SSX1, 2, or 4 genes on the X chromosome.We report a case of primary pericardial synovial sarcoma in a 42-year-old man with dyspnea. Imaging studies showed an 8.0 x 4.8 cm enhancing pericardial mass compressing the left atrium and a large pericardial effusion with compression effect consistent with tamponade. The patient underwent partial surgical resection of the mass. Histologic examination revealed an invasive malignant neoplasm with fascicles and sheets of uniform spindle cells with pleomorphic nuclei and many mitoses (7 per 10 HPF). This monophasic pattern raises a differential diagnosis including synovial sarcoma, fibrosarcoma, epithelial sarcoma, and leiomyosarcoma. The diagnosis of synovial sarcoma was confirmed by interphase FISH on FFPE tissue with an SS18 break-apart probe that was positive for an SS18 rearrangement. The patient underwent adjuvant chemotherapy and radiotherapy. He survives at 9 months after diagnosis with residual tumor growing rapidly. A review of the literature reveals 40 case reports of primary synovial sarcoma of the heart. The mean age is 36 years with a M/F ratio of 2.25. The most common locations are pericardium (13 cases) and right atria (12). Seventeen cases are monophasic type, of which 11 have confirmed t(X;18) translocations by cytogenetics, FISH, and/or RT-PCR. The prognosis is poor; 11 patients died during the first year after diagnosis. FISH provides a valuable tool for the diagnosis of synovial sarcoma, especially for challenging cases in uncommon locations (eg, heart). Identification of patients with the SS18 translocation is important for future targeted therapies

CONTEXT: Data regarding effects of lower-dose GH on cardiopulmonary function in GH-deficient (GHD) adults are limited. OBJECTIVES: The objective was to assess effects of lower-dose GH on exercise capacity and echocardiographic parameters in GHD adults. DESIGN: The study was a 6-month double-blind, placebo-controlled randomized trial. SETTING: The study was conducted at the General Clinical Research Center. PARTICIPANTS: Thirty hypopituitary adults with GHD were studied. INTERVENTION: Subjects were randomized to recombinant human GH or placebo for 6 months, followed by open-label recombinant human GH for 12 months. MAIN OUTCOME MEASURES: Primary endpoints were exercise duration, maximal oxygen consumption, and left ventricular ejection fraction. Secondary endpoints were echocardiographic indices of systolic and diastolic function, left ventricular mass, lipids, and body composition. RESULTS: In the 6-month double-blind phase, mean GH dose was 0.64 mg/d. Mean IGF-I sd score increased from -4.5 to -1.0. Exercise duration, maximal oxygen consumption, left ventricular ejection fraction, and other echocardiographic parameters were normal at baseline and did not change. GH decreased total and low-density lipoprotein cholesterol by 7.5% (P = 0.016) and 14.7% (P = 0.002) (P = 0.04 vs. placebo). Mean lean body mass increased by 2.2 kg (P = 0.004), fat mass decreased by 1.7 kg (P = 0.21), and percent body fat decreased by 2.5% (P = 0.018), although between-group changes were not significant. CONCLUSIONS: Human GH did not improve exercise performance or echocardiographic parameters or decrease fat mass but significantly decreased total and low-density lipoprotein cholesterol, increased IGF-I, and increased lean body mass. These results indicate that responses to human GH are variable and should be assessed at baseline and during treatment

BACKGROUND: Darinaparsin is a novel organic arsenic that reaches higher intracellular concentration with decreased toxicity compared to inorganic arsenic. We conducted a multi-center phase II study with darinaparsin in patients with advanced HCC. METHODS: Eligibility criteria included unresectable or metastatic measurable HCC, up to two prior systemic treatments, ECOG performance status < or = 2, Child Pugh Class A or B and adequate organ functions. Darinaparsin was administered at 420 mg/m(2) intravenously, twice weekly at least 72 h apart for 3 weeks in a 4-week cycle. The primary end point was response rate. A Simon two-stage design was used. RESULTS: Among 15 patients in the first stage, no objective responses were observed. Two patients had stable disease. The median number of cycles on study per patient was 2 (1-6). The median progression free survival and overall survival were 55 days (95% confidence interval: 50-59) and 190 days (95% confidence interval: 93-227), respectively. No treatment related hospitalizations or deaths occurred. Treatment related grade 1-2 toxicities included nausea, vomiting (26.7% each), fatigue (20%), anorexia and diarrhea (13.3% each). Grade 3 anorexia, wheezing, agitation, abdominal pain and SGPT were observed in 1 patient each (6.7%). One patient experienced grade 4 hypoglycemia (6.7%). CONCLUSIONS: Darinaparsin could be safely administered with tolerable toxicity profiles, and no QTc prolongation in patients with advanced HCC. However, at this dose and schedule, it has shown no objective responses in HCC and this trial was terminated as planned after the first stage of efficacy analysis

BACKGROUND: Coronary artery disease (CAD) is the most common cause of left ventricular systolic dysfunction (LVSD). Patients with ischemia as the cause of LVSD may warrant revascularization. Angiography is the most accurate method of CAD diagnosis but is invasive, expensive, and associated with some risk. Noninvasive imaging for CAD often involves expensive equipment, radiation exposure, medication, and/or contrast administration. Carotid ultrasound with measurement of intima-media thickness (IMT) is safe and inexpensive. Carotid IMT is well correlated with the presence of CAD. We assessed the accuracy of carotid ultrasound for identification of CAD as a potential etiology of LVSD. METHODS: Patients with LVSD (ejection fraction < or =40%) of uncertain etiology referred for angiography underwent carotid ultrasound. Patients with history of myocardial infarction were excluded. Two experienced cardiologists blinded to CAD status determined common carotid artery (CCA) IMT and plaque. Significant CAD was defined as > or =50% stenosis of any major artery. Ischemic LVSD was defined as (1) left main and/or proximal left anterior descending coronary artery > or =75% or (2) > or =2 major arteries with > or =75% stenosis. RESULTS: Mean ejection fraction was 27% +/- 10% in 150 patients. Significant CAD was found in 64 (42.7%) and ischemic LVSD in 40 (26.7%). Carotid plaque was seen in 95 (63.3%). Mean CCA IMT was > or =0.9 mm in 69 (46.0%). The combination of mean CCA IMT <0.9 mm and no plaque had negative predictive value for ischemic LVSD of 98%. CONCLUSIONS: Carotid ultrasound with IMT measurement is a valuable screening tool for excluding an ischemic etiology of LVSD when CAD is suspected

An unusual case of total anomalous pulmonary venous connection surviving to adulthood without surgical correction is presented. Transthoracic echocardiography first led to this diagnosis and magnetic resonance imaging refined the anatomic diagnosis leading to successful surgical correction

OBJECTIVE: The inflammatory process of aortic stenosis involves the differentiation of aortic valve myofibroblasts into osteoblasts. Osteopontin, a proinflammatory glycoprotein, both stimulates differentiation of myofibroblasts and regulates the deposition of calcium by osteoblasts. Osteopontin levels are increased in patients with such conditions as end-stage renal disease, ectopic calcification, and autoimmune disease. We hypothesized that increased plasma osteopontin levels might be associated with the presence of aortic valve calcification and stenosis. METHODS: Venous blood from volunteers older than 65 years undergoing routine echocardiographic analysis or aortic valve surgery for aortic stenosis was collected. Plasma osteopontin levels were measured by means of enzyme-linked immunosorbent assay. The presence of aortic stenosis was defined as an aortic valve area of less than 2.0 cm(2). Aortic valve calcification was assessed by using a validated echocardiographic grading system (1, none; 2, mild; 3, moderate; 4, severe). Comparisons were performed with nonpaired t tests. RESULTS: Aortic stenosis was present in 23 patients (mean age, 78 years) and was absent in 7 patients (mean age, 72 years). Aortic valve calcification scores were 3.5 +/- 0.6 and 1.3 +/- 0.5 in patients with and without aortic stenosis, respectively (P < .001). Patients with no or mild aortic valve calcification had lower osteopontin levels compared with patients with moderate or severe aortic valve calcification (406.1 +/- 165.8 vs 629.5 +/- 227.5 ng/mL, P = .01). Similarly, patients with aortic stenosis had higher osteopontin levels compared with patients without aortic stenosis (652.2 +/- 218.7 vs 379.7 +/- 159.9 ng/mL, P < .01). CONCLUSION: Increased levels of plasma osteopontin are associated with the presence of aortic valve calcification and stenosis. These findings suggest that osteopontin might play a functional role in the pathogenesis of calcific aortic stenosis