Predictors of clinical efficacy of 'Ablate and Pace' therapy in patients with permanent atrial fibrillation.

OBJECTIVE: To evaluate the 2-year clinical improvement after 'Ablate and Pace' therapy and to identify the variables able to influence the efficacy of this therapy in patients with permanent atrial fibrillation (AF). Design Prospective multicentre observational study. Setting Cardiology departments of 19 general hospitals in Italy, Spain and Greece. PATIENTS: 171 patients with drug-refractory severely symptomatic permanent AF considered for AV junction ablation. Interventions Patients underwent AV junction ablation, received a right ventricular (RV) pacing or echo-guided cardiac resynchronisation (CRT) pacing and were followed-up to 24 months. Main outcome measures Non-responders to Ablate and Pace therapy were defined those patients who, during the follow-up period had clinical failure (defined as death or hospitalisation due to heart failure, or worsening heart failure) or showed no improvement in their clinical condition. RESULTS: Responders were 63% of RV-paced patients and 83% of CRT-paced patients. Another 27% showed no clinical improvement (7%) or worsened (20%) (non-responders group). On multivariable Cox regression analysis, CRT mode and echo-optimised CRT were the only independent protective factors against non-response (HR=0.24, 95% CI 0.10-0.58, p=0.001 and HR=0.22, 95% CI 0.07-0.77, p=0.018 respectively). On comparing freedom from non-response, a trend in favour of echo-optimised CRT versus simultaneous biventricular pacing (p=0.077) was seen. CONCLUSIONS: In patients affected by severely symptomatic permanent AF, Ablate and Pace therapy yielded a clinical benefit in 63% of RV-paced patients and 83% of CRT-paced patients. CRT pacing and echo-optimised CRT were the only independent predictor of clinical benefit.

Left ventricular myocardial mass determination by contrast enhanced colour Doppler compared with magnetic resonance imaging.

OBJECTIVE: To assess the feasibility of using contrast enhanced colour Doppler echocardiography to determine left ventricular (LV) mass and to compare its accuracy with LV mass obtained by magnetic resonance imaging (MRI). METHODS: Images were acquired in the short axis plane of the heart, derived from coronal and sagittal scout views and double oblique angulation. The LV mass was calculated by two methods: Simpson's rule and the area-length method. Levovist (Schering AG, Berlin, Germany) 2.5 g was given by slow intravenous bolus or infusion over about 45 seconds for contrast imaging. LV images were captured in the apical two chamber, four chamber, and three chamber views. Each contrast harmonic colour Doppler image was converted to a cavity-only image by simple image mathematics. RESULTS: 27 (77.1%) of the patients (mean (SD) age 66.2 (8.9) years) were men. There was a mean (SD) interval of 6.6 (8.6) days (range 0-27 days) between echocardiography and MRI. The mean (SD) LV mass determined by MRI Simpson's rule method was 171.0 (52.4) g (range 105.1-318.7 g). The mean LV mass (SD) determined by the echocardiographic Simpson's rule method was 178.2 (47.0) g (range 112.6-307.6 g). The mean (SD) MRI area-length LV mass was 187.3 (64.5) g (range 109.0-393.6 g). The linear regression correlation between LV mass determined by MRI Simpson's and echocardiographic Simpson's methods was excellent (y = 1.022x, R2 = 0.986) with a mean (SD) difference of 7.20 (20.9) g. The linear regression correlation between the MRI area-length LV mass and MRI Simpson's LV mass was excellent (y = 1.101x, R2 = 0.989) with a mean (SD) difference of 16.3 (22.3) g. CONCLUSIONS: LV mass may be obtained reliably by contrast enhanced colour Doppler and two dimensional echocardiography. The contrast Doppler method accurately determines LV mass with excellent agreement with the MRI technique.

Blunted coronary flow reserve in systemic sclerosis.

OBJECTIVES: We investigated whether the non-invasive determination of coronary flow reserve (CFR), as evaluated by transthoracic Doppler echocardiography, might be a potential method to detect early dysfunction of cardiovascular system in patients affected by systemic sclerosis (SSc) without clinical signs or symptoms of cardiac impairment. The possible correlations between the CFR values and the duration of the disease, specific autoantibodies and cutaneous involvement subsets were investigated. METHODS: Forty-four consecutive patients affected by SSc were analysed. The CFR was detected in the distal left anterior descending coronary artery by contrast-enhanced transthoracic second harmonic Doppler in all SSc patients and in 16 healthy controls. CFR was assessed at rest and during hyperaemia induced by administration of adenosine at 0.14 mg/kg/min over 5 min. The CFR was calculated as the ratio between hyperaemic (peak adenosine infusion) and resting peak diastolic velocity (PdvCFR) and resting velocity time integral (VtiCFR). Past medical history was carefully investigated. RESULTS: Both PdvCFR and VtiCFR were significantly reduced in SSc patients when compared with controls (P<0.0001). In particular, both PdvCFR and VtiCFR were significantly lower in patients with dSSc when compared with patients affected by lSSc (P<0.02 and P<0.04 respectively). No statistically significant correlation was found between CFR values and history of smoking, serum levels of cholesterol or triglycerides, blood pressure, age of patients, duration of SSc and serum autoantibody positivity for ANA, ACA and Scl70. CONCLUSIONS: CFR is often reduced in SSc patients. CFR was lower in patients with dSSc than in those affected by lSSc. A reduced CFR value should be considered an indirect sign of heart involvement in scleroderma, but its clinical and prognostic implications need to be clarified.

Fatty acid synthase expression in melanoma.

BACKGROUND: Fatty acid synthase (FAS), the key enzyme responsible for the synthesis of fatty acids, is weakly expressed in some normal human tissues. Recently, FAS has been demonstrated to be overexpressed in many non-neoplastic highly proliferative lesions and in aggressive carcinomas with poor outcome, including colon, breast and ovary carcinomas. METHODS: In order to evaluate the prognostic significance of FAS in human melanoma, we analysed by means of immunohistochemistry, using a monoclonal anti-FAS antibody, 77 primary melanomas and 30 nodal and cutaneous metastasis. Thirty nevi (15 dermal and 15 junctional nevi) were used as controls. All patients were followed-up for 5 years. RESULTS: Thirty-four melanomas expressed strong FAS immunostaining; the remaining 43 cases showed weak expression or were negative. All cutaneous and nodal metastasis were strongly positive. All patients with metastases deceased during the follow up period. Control specimens expressed weak staining. None of these patients developed recurrence. Statistical analysis revealed significant association of FAS expression with Breslow thickness (p = 0.012). The intensity of FAS immunostaining was also predictive of prognosis (p = 0.049). CONCLUSIONS: FAS is a reliable prognostic marker in human melanomas. FAS predictive strength is increased when associated with Breslow thickness. The observation of FAS in human melanomas may stratify patients for stricter follow-ups and suggest different therapeutic approaches.

Immunohistochemical expression of human erythrocyte glucose transporter and fatty acid synthase in infiltrating breast carcinomas and adjacent typical/atypical hyperplastic or normal breast tissue.

To evaluate the immunohistochemical expression of GLUT1, human erythrocyte glucose transporter 1, and fatty acid synthase (FAS), 66 human breast carcinomas and adjacent peritumoral tissue were studied. GLUT1 and FAS were expressed in 53 and 61 carcinomas, in 17 and 14 typical/atypical hyperplastic tissues, and in 16 and 13 tissues adjacent to tumor normal breast tissue, respectively. Statistical analysis revealed association between invasive carcinomas, invasive carcinomas with in situ component and GLUT1 immunostaining. GLUT1 staining was associated with tumor grade, FAS with tumor stage, and GLUT1 and FAS coexpression with tumor grade. Controls expressed no immunostaining. GLUT1 and FAS are new markers involved in the biologic activities of cancer cells. GLUT1 and FAS coexpression may indicate increased use of energy by the neoplastic cells correlated with poorly differentiated features and aggressive behavior. The innovative finding that GLUT1 and FAS are observed in mammary carcinoma adjacent nonneoplastic tissues may suggest a role in detecting initial phases of breast carcinogenesis.

[Malignant phyllode tumor of the breast with features of intraductal carcinoma]. / Tumore filloide maligno della mammella con aspetti di carcinoma intraduttale.

Malignant phyllode tumor is a rare biphasic breast tumor consisting of a malignant mesenchymal component and an epithelial component that is usually benign. We report an unusual case of a malignant phyllode tumor of the breast with neoplastic features of both the epithelial and stromal components. The patient was a 39-year-old woman with family history for breast carcinoma. Grossly, the excised tumor was a 9 x 7 x 5.5 cm gray lobulated mass with infiltrative margins and necrotic-hemorrhagic areas. Histologically the tumor consisted mainly of neoplastic mesenchyme with non invasive comedo, cribriform and micropapillary features of the ducts. Three months after the excision of the neoplastic mass, the patient developed an infiltrating ductal carcinoma of the opposite breast. Hereditary and bilateral tumors are commonly associated with germline mutations. Tissue from both neoplasms however did not express either BRCA1 or BRCA2 mutations.

Immunohistochemical study of fatty acid synthase in ovarian neoplasms.

In order to evaluate the prognostic significance of fatty acid synthase (FAS), the key enzyme in fatty acid biosynthesis, in ovarian benign and malignant tumors 98 patients with ovarian masses were immunohistochemically evaluated. Histologic features of the lesions and expression for FAS were statistically associated with clinical data and disease-free survival over a 5-year follow-up period. The mean age of patients was 65 years. TNM surgical stages were I in 31.8%, II in 28.2% and III in 40% of cases. The 5-year disease-free survival of the 85 malignant common epithelial ovarian tumors was 47.1% while 35.3 of patients died with active disease. Seventy-eight (79.6%) out of 98 cases expressed FAS in the neoplastic epithelial cells and 42 (42.9%) in the non-neoplastic stromal cells. Statistical analysis revealed FAS expression and stage of the disease to be significantly correlated to recurrence and survival rates only in the malignant common epithelial tumors. Moreover, multivariate analysis showed FAS expression (p=0.05) and tumor stage (p=0.03) to be independent prognostic predictors. FAS is a reliable predictor of recurrence and disease-free survival in common epithelial ovarian tumors along with neoplastic stage. Clinical data, other histologic subtypes and grading were not statistically significant.