Head of Westport, MA, United States
Head of Westport, MA, United States

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Afilalo J.,Cardiac Ultrasound Laboratory | Flynn A.W.,Cardiac Ultrasound Laboratory | Shimony A.,Cardiac Ultrasound Laboratory | Rudski L.G.,Cardiac Ultrasound Laboratory | And 4 more authors.
Circulation | Year: 2013

BACKGROUND - Although echocardiography is commonly performed before coronary artery bypass surgery, there has yet to be a study examining the incremental prognostic value of a complete echocardiogram. METHODS AND RESULTS - Patients undergoing isolated coronary artery bypass surgery at 2 hospitals were divided into derivation and validation cohorts. A panel of quantitative echocardiographic parameters was measured. Clinical variables were extracted from the Society of Thoracic Surgeons database. The primary outcome was in-hospital mortality or major morbidity, and the secondary outcome was long-term all-cause mortality. The derivation cohort consisted of 667 patients with a mean age of 67.2±11.1 years and 22.8% females. The following echocardiographic parameters were found to be optimal predictors of mortality or major morbidity: severe diastolic dysfunction, as evidenced by restrictive filling (odds ratio, 2.96; 95% confidence interval, 1.59-5.49), right ventricular dysfunction, as evidenced by fractional area change <35% (odds ratio, 3.03; 95% confidence interval, 1.28-7.20), or myocardial performance index >0.40 (odds ratio, 1.89; 95% confidence interval, 1.13-3.15). These results were confirmed in the validation cohort of 187 patients. When added to the Society of Thoracic Surgeons risk score, the echocardiographic parameters resulted in a net improvement in model discrimination and reclassification with a change in c-statistic from 0.68 to 0.73 and an integrated discrimination improvement of 5.9% (95% confidence interval, 2.8%-8.9%). In the Cox proportional hazards model, right ventricular dysfunction and pulmonary hypertension were independently predictive of mortality over 3.2 years of follow-up. CONCLUSIONS - Preoperative echocardiography, in particular right ventricular dysfunction and restrictive left ventricular filling, provides incremental prognostic value in identifying patients at higher risk of mortality or major morbidity after coronary artery bypass surgery. © 2012 American Heart Association, Inc.

Schwartz D.R.,University of Pennsylvania | Briggs E.R.,University of Pennsylvania | Qatanani M.,University of Pennsylvania | Qatanani M.,Merck And Co. | And 5 more authors.
Endocrinology | Year: 2013

Resistin is a circulating mediator of insulin resistance mainly expressed in human monocytes and responsive to inflammatory stimuli. Recent clinical studies have connected elevated resistin levels with the development and severity of heart failure. To further our understanding of the role of human resistin in heart failure, we studied a humanized mouse model lacking murine resistin but transgenic for the human Retn gene (Hum-Retn mice), which exhibits basal and inflammationstimulated resistin levels similar to humans. Specifically, we explored whether resistin underlies acute anthracycline-induced cardiotoxicity. Remarkably, doxorubicin (25mg/kg ip) led to a 4-fold induction of serum resistin levels in Hum-Retn mice. Moreover, doxorubicin-induced cardiotoxicity was greater in the Hum-Retn mice than in littermate controls not expressing human resistin (Retn-/-). Hum-Retn mice showed increased cardiac mRNA levels of inflammatory and cell adhesion genes compared with Retn-/- mice. Macrophages, but not cardiomyocytes, from Hum-Retn mice treated with doxorubicin in vitro showed dramatic induction of hRetn (human resistin) mRNA and protein expression. We also examined resistin levels in anthracycline-treated breast cancer patients with and without cardiotoxicity. Intriguingly, serum resistin levels in women undergoing anthracyclinecontaining chemotherapy increased significantly at 3 months and remained elevated at 6 months in those with subsequent cardiotoxicity. Further, elevation in resistin correlated with decline in ejection fraction in these women. These results suggest that elevated resistin is a biomarker of anthracycline-induced cardiotoxicity and may contribute in the development of heart failure via its direct effects on macrophages. These results further implicate resistin as a link between inflammation, metabolism, and heart disease. Copyright © 2013 by The Endocrine Society.

Chu J.W.,Cardiac Ultrasound Laboratory | Picard M.H.,Cardiac Ultrasound Laboratory | Agnihotri A.K.,Harvard University | Fitzsimons M.G.,Harvard University
Echocardiography | Year: 2010

Background: This study aimed to assess the accuracy of two-dimensional echocardiography (echo) in diagnosing unicuspid aortic valve (UAV) and to determine echo features that could improve the diagnosis. Method: We reviewed transthoracic/transesophageal echoes (TTE/TEE) from our hospital database for adult patients who had aortic valve surgery with a preoperative echo diagnosis of UAV or equivocal diagnosis of bicuspid aortic valve (BAV) BAV/UAV. Morphological characteristics of AV and ascending aortic dimensions were evaluated. Results: Nineteen patients were identified, 13 (11 Male, 2 Female, mean age 47 ± 10 years) had surgically confirmed diagnosis of UAV, six had BAV. The incidence of UAV was 2.6%. For diagnosing UAV, the sensitivity and specificity of TTE was 27% and 50% and those of TEE was 75% and 86%, respectively. For TTE, positive predictive value (PPV) was 60% and negative predictive value (NPV) was 20%. By TEE, PPV was 90% and the NPV was 67%. In UAV patients, 85% had severe aortic stenosis (mean gradient 45 ± 16 mmHg, AVA: 0.9 ± 0.2 cm 2). 46% had ascending aorta aneurysm (mean aortic root, sinutubular junction, ascending aorta dimensions: 36 ± 3 mm, 31 ± 4 mm and 41 ± 8 mm). Patients with ascending aortic aneurysm were younger (41 ± 11 years vs. 52 ± 5 years, P < 0.05) All UAV were unicommissural with a posteriorly positioned commissural attachment, 69% were heavily calcified. Diagnostic accuracy was limited by quality of images, severity, and distribution of calcification. Conclusion: TEE is the diagnostic modality of choice in UAV. Identifying several echo features may improve its diagnostic accuracy. © 2010, Wiley Periodicals, Inc.

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