BackgroundHost factors and complications have been associated with higher mortality in infective endocarditis (IE). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE.Methods and ResultsUsing a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ICE]–Prospective Cohort Study [PCS], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry (ICE‐PLUS, 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE‐PCS cohort and 342 of 1197 (28.6%) in the ICE‐PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE, causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables.ConclusionsSix‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE.

Background-We investigated the feasibility and efficacy of polyethylenimine (PEI) based human vascular endothelial growth factor-165 (hVEGF 165 ) gene transfer into human skeletal myoblasts (HSM) for cell based delivery to the infarcted myocardium. Methods and Results-Based on optimized transfection procedure using enhanced green fluorescent protein (pEGFP), HSM were transfected with plasmid-hVEGF 165 (phVEGF 165 ) carried by PEI (PEI-phVEGF 165 ) nanoparticles. The transfected HSM were characterized for transfection and expression of hVEGF 165 in vitro and transplanted into rat heart model of acute myocardial infarction (AMI): group-1ϭDMEM injection, group-2ϭ HSM transplantation, group-3ϭ PEI-phVEGF 165 -transfected HSM (PEI-phVEGF 165 myoblast) transplantation. A total of 48 rats received cyclosporine injection from 3 days before and until 4 weeks after cell transplantation. Echocardiography was performed to assess the heart function. Animals were sacrificed for molecular and histological studies on the heart tissue at 4 weeks after treatment. Based on optimized transfection conditions, transfected HSM expressed hVEGF 165 for 18 days with Ͼ90% cell viability in vitro. Apoptotic index was reduced in group-2 and group-3 as compared with group-1. Blood vessel density (ϫ400) by immunostaining for PECAM-1 in group-3 was significantly higher (Pϭ0.043 for both) as compared with group-1 and group-2 at 4 weeks. Regional blood flow (ml/min/g) in the left ventricular anterior wall was higher in group-3 (Pϭ0.043 for both) as compared with group-1 and group-2. Improved ejection fraction was achieved in group-3 (58.44Ϯ4.92%) as compared with group-1 (Pϭ0.004). Conclusion-PEI

In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Tan RS, Kassab G. Right ventricular regional wall curvedness and area strain in patients with repaired tetralogy of Fallot. Am J Physiol Heart Circ Physiol 302: H1306 -H1316, 2012. First published December 30, 2011 doi:10.1152/ajpheart.00679.2011.-A quantitative understanding of right ventricular (RV) remodeling in repaired tetralogy of Fallot (rTOF) is crucial for patient management. The objective of this study is to quantify the regional curvatures and area strain based on three-dimensional (3-D) reconstructions of the RV using cardiac magnetic resonance imaging (MRI). Fourteen (14) rTOF patients and nine (9) normal subjects underwent cardiac MRI scan. 3-D RV endocardial surface models were reconstructed from manually delineated contours and correspondence between end-diastole (ED) and end systole (ES) was determined. Regional curvedness (C) and surface area at ED and ES were calculated as well as the area strain. The RV shape and deformation in rTOF patients differed from normal subjects in several respects. Firstly, the curvedness at ED (mean for 13 segments, 0.030 Ϯ 0.0076 vs. 0.029 Ϯ 0.0065 mm Ϫ1 ; P Ͻ 0.05) and ES (mean for 13 segments, 0.040 Ϯ 0.012 vs. 0.034 Ϯ 0.0072 mm Ϫ1 ; P Ͻ 0.001) was decreased by chronic pulmonary regurgitation. Secondly, the surface area increased significantly at ED (mean for 13 segments, 982 Ϯ 192 vs. 1,397 Ϯ 387 mm 2 ; P Ͻ 0.001) and ES (mean for 13 segments, 576 Ϯ 130 vs. 1,012 Ϯ 302 mm 2 ; P Ͻ 0.001). In particular, rTOF patients had significantly larger surface area than that in normal subjects in the free wall but not for the septal wall. Thirdly, area strain was significantly decreased (mean for 13 segments, 56 Ϯ 6 vs. 34 Ϯ 7%; P Ͻ 0.0001) in rTOF patients. Fourthly, there were increases in surface area at ED (5,726 Ϯ 969 vs. 6,605 Ϯ 1,122 mm 2 ; P Ͻ 0.05) and ES (4,280 Ϯ 758 vs. 5,569 Ϯ 1,112 mm 2 ; P Ͻ 0.01) and decrease in area strain (29 Ϯ 8 vs. 18 Ϯ 8%; P Ͻ 0.001) for RV outflow tract. These findings suggest significant geometric and strain differences between rTOF and normal subjects that may help guide therapeutic treatment. magnetic resonance imaging; curvature; right ventricular remodeling; deformation; three-dimensional reconstruction TETRALOGY OF FALLOT (TOF) is the most common cyanotic congenital heart disease (19). The main features include ventricular septum defect, subpulmonary stenosis, and overriding aorta and right ventricular (RV) hypertrophy. Surgical repair is usually performed in early infancy to widen the passage from the RV to the pulmonary artery and close the ventricular septal defect. This ensures separation of oxygen-rich and oxygenpoor blood flows to the proper chambers. Surgical repair of TOF often involves disruption of pulmonary valve integrity that leads to pulmonary regurgitation (PR; Refs. 8, 37). This in turn causes RV dilation (9, 23) and RV outflow tract (RVOT) aneurysm (2-3, 13, 28 -29). The RV dilation is usually tolerated with little or no symptoms during the first two to three decades of age. If left untreated, however, continued...

Ischemic heart disease (IHD) is the leading cause of disability and mortality worldwide. Reactive oxygen species (ROS) have been shown to play key roles in the progression of diabetes, hypertension, and hypercholesterolemia, which are independent risk factors that lead to atherosclerosis and the development of IHD. Engineered biomaterial‐based nanomedicines are under extensive investigation and exploration, serving as smart and multifunctional nanocarriers for synergistic therapeutic effect. Capitalizing on cell/molecule‐targeting drug delivery, nanomedicines present enhanced specificity and safety with favorable pharmacokinetics and pharmacodynamics. Herein, the roles of ROS in both IHD and its risk factors are discussed, highlighting cardiovascular medications that have antioxidant properties, and summarizing the advantages, properties, and recent achievements of nanomedicines that have ROS scavenging capacity for the treatment of diabetes, hypertension, hypercholesterolemia, atherosclerosis, ischemia/reperfusion, and myocardial infarction. Finally, the current challenges of nanomedicines for ROS‐scavenging treatment of IHD and possible future directions are discussed from a clinical perspective.