bluuebunny/crossref_metadata_2025 huggingface dataset:
A Critical Reappraisal of the Ross Operation
Authors: Sievers Hans H. , Hanke Thorsten , Stierle Ulrich , Bechtel Matthias F. , Graf Bernhard , Robinson Derek R. , Ross Donald N.
Published: July 2006

Background—

The autograft procedure, an option in aortic valve replacement, has undergone technical evolution. A considerable debate about the most favorable surgical technique in the Ross operation is still ongoing. Originally described as a subcoronary implant, the full root replacement technique is now the most commonly used technique to perform the Ross principle.

Methods and Results—

Between June of 1994 and June of 2005, the original subcoronary autograft technique was performed in 347 patients. Preoperative, perioperative, and follow-up data were collected and analyzed. Mean patient age at implantation was 44±13 years (range 14 to 71 years; 273 male, 74 female). Bicuspid valve morphology was present in 67%. The underlying valve disease was aortic regurgitation in 111 patients, stenosis in 46 patients, combined lesion in 188 patients, and active endocarditis in 22 patients (in 2 patients without stenosis or regurgitation). Concomitant procedures were performed in 130 patients. Clinical and echocardiographic follow-up visits were obtained annually (mean follow up 3.9±2.7 years, 1324 patient-years; completeness of follow-up 99.4%). The in-hospital mortality rate was 0.6% (n =2), and the late mortality was 1.7% (n=6), with 5 noncardiac deaths (4 cancer, 1 multiorgan failure after noncardiac surgery) and 1 cardiac death (sudden death). At last follow-up, 94% of the surviving patients were in New York Heart Association class I. Ross procedure–related valvular reoperations were necessary in 9 patients: Three received autograft explants, 5 received homograft explants, and 1 received a combined auto- and homograft explant. At last follow-up visit, autograft/homograft regurgitation grade II was present in 5/10 patients and grade III in 4/0. Maximum/mean pressure gradients were 7.4±6.2/3.7±2.1 mm Hg across the autograft and 15.3±9.4/7.6±5.0 mm Hg across the right ventricular outflow tract, respectively. Aortic root dilatation was not observed. Freedom from any valve-related intervention was 95% at 8 years (95% confidence interval 91% to 99%).

Conclusion—

Midterm follow-up of autograft procedures according to the original Ross subcoronary approach proves excellent clinical and hemodynamic results, with no considerable reoperation rates. Revival of the original subcoronary Ross operation should be taken into account when considering the best way to install the Ross principle.
High-Dose β-Blockers and Tight Heart Rate Control Reduce Myocardial Ischemia and Troponin T Release in Vascular Surgery Patients
Authors: Feringa Harm H.H. , Bax Jeroen J. , Boersma Eric , Kertai Miklos D. , Meij Simon H. , Galal Wael , Schouten Olaf , Thomson Ian R. , Klootwijk Peter , van Sambeek Marc R.H.M. , Klein Jan , Poldermans Don
Published: July 2006

Background—

Adverse perioperative cardiac events occur frequently despite the use of beta (β)-blockers. We examined whether higher doses of β-blockers and tight heart rate control were associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome.

Methods and Results—

In an observational cohort study, 272 vascular surgery patients were preoperatively screened for cardiac risk factors and β-blocker dose. Beta-blocker dose was converted to a percentage of maximum recommended therapeutic dose. Heart rate and ischemic episodes were recorded by continuous 12-lead electrocardiography, starting 1 day before to 2 days after surgery. Serial troponin T levels were measured after surgery. All-cause mortality was noted during follow-up. Myocardial ischemia was detected in 85 of 272 (31%) patients and troponin T release in 44 of 272 (16.2%). Long-term mortality occurred in 66 of 272 (24.2%) patients. In multivariate analysis, higher β-blocker doses (per 10% increase) were significantly associated with a lower incidence of myocardial ischemia (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.51 to 0.75), troponin T release (HR, 0.63; 95% CI, 0.49 to 0.80), and long-term mortality (HR, 0.86; 95% CI, 0.76 to 0.97). Higher heart rates during electrocardiographic monitoring (per 10-bpm increase) were significantly associated with an increased incidence of myocardial ischemia (HR, 2.49; 95% CI, 1.79 to 3.48), troponin T release (HR, 1.53; 95% CI, 1.16 to 2.03), and long-term mortality (HR, 1.42; 95% CI, 1.14 to 1.76).

Conclusion—

This study showed that higher doses of β-blockers and tight heart rate control are associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome in vascular surgery patients.
The Impact of the Capability of Circulating Progenitor Cell to Differentiate on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction
Authors: Numaguchi Yasushi , Sone Takahito , Okumura Kenji , Ishii Masakazu , Morita Yasuhiro , Kubota Ryuji , Yokouchi Kazuhiko , Imai Hajime , Harada Mitsunori , Osanai Hiroyuki , Kondo Takahisa , Murohara Toyoaki
Published: July 2006

Background—

Circulating endothelial progenitor cells (EPCs) are known to be involved in vasculogenesis and mobilized after acute myocardial infarction (AMI). To test the hypothesis that the angiogenic function of EPCs affects post-myocardial infarction (MI) myocardial salvage, we evaluated the number and potential differentiation of EPCs and compared these data with clinical parameters 6 months after MI.

Methods and Results—

Consecutive 51 patients (age, 61±8 years, mean±SD) with primary AMI who were successfully treated with stenting were enrolled. EPC identified as CD45
low
, CD34
+
, CD133
+
, and VEGFR2
+
was quantified by a flow cytometry. The potential of EPCs to differentiate into endothelial cells (EPC differentiation) was also confirmed by the upregulation of CD31 and VEGFR2 after 7 days of culture. According to the proportion of EPC fraction, patients were divided into 2 groups (cut-off value=median). Although no difference was seen in myocardial damage shown by mean peak CK leakage and mean area at risk between the differentiated group (n=26) and nondifferentiated group (n=25), the number of attached cell was greater in differentiated group than in the nondifferentiated group (
P
=0.023). Left ventricular function and ischemic damaged area were assessed by scintigraphic images of
123
I-BMIPP in the acute phase and
99m
Tc-tetrofosmin in the chronic phase. We found that a greater increase in myocardial salvage (
P
=0.0091), decrease in end-systolic volume (
P
=0.012), and recovery of ejection fraction (
P
=0.011) occurred in the group with differentiated EPCs than in the nondifferentiated group.

Conclusions—

In patients with primary AMI, the capability of EPCs to differentiate influences the functional improvement and infarct size reduction, indicating that manipulation of EPCs could be a novel therapeutic target to salvage ischemic damage.
Perioperative Increases in Serum Creatinine Are Predictive of Increased 90-Day Mortality After Coronary Artery Bypass Graft Surgery
Authors: Brown Jeremiah R. , Cochran Richard P. , Dacey Lawrence J. , Ross Cathy S. , Kunzelman Karyn S. , Dunton Robert F. , Braxton John H. , Charlesworth David C. , Clough Robert A. , Helm Robert E. , Leavitt Bruce J. , MacKenzie Todd A. , O’Connor Gerald T.
Published: July 2006

Background—

Impaired renal function after coronary artery bypass graft (CABG) surgery is a key risk factor for in-hospital mortality. However, perioperative increases in serum creatinine and the association with mortality has not been well-studied. We assessed the hypothesis that perioperative increases in creatinine are associated with increased 90-day mortality.

Methods and Results—

We studied 1391 patients in northern New England undergoing CABG in 2001 and evaluated preoperative and postoperative creatinine. Patients with preoperative dialysis were excluded. Data were linked to the National Death Index to assess 90-day survival. Kaplan-Meier and log-rank techniques were used. Patients were stratified by percent increase in creatinine from baseline: <25%, 25% to 49%, 50% to 99%, ≥100%. We assessed 90-day survival and calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for creatinine groups, adjusting for age and sex. Patients with the largest creatinine increases (50% to 99% or ≥100%) had significantly higher 90-day mortality compared with patients with a smaller increase (<50%;
P
<0.001). Adjusted HR and 95% CI confirmed patients in the higher 2 groups had an increased risk of mortality compared with the <25% (referent); however, the 25% to 49% group was not different from the referent: 1.80 (95% CI: 0.73 to 4.44), 6.57 (95% CI, 3.03 to 14.27), and 22.10 (95% CI, 11.25 to 43.39).

Conclusions—

Patients with large creatinine increases (≥50%) after CABG surgery have a higher 90-day mortality compared with patients with small increases. Efforts to identify patients with impaired renal function and to preserve renal function before cardiac surgery may yield benefits for patients in the future.
How Does Glucose Insulin Potassium Improve Hemodynamic Performance?
Authors: Ranasinghe Aaron M. , McCabe Christopher J. , Quinn David W. , James Sally R. , Pagano Domenico , Franklyn Jayne A. , Bonser Robert S.
Published: July 2006

Background—

Glucose insulin potassium (GIK) improves hemodynamic performance after coronary artery surgery (CABG). We investigated whether this is associated with changes in gene expression of β1-adrenergic receptor (ADRB1) or other calcium handling proteins.

Methods and Results—

During a randomized double-blind placebo-controlled trial, 48 patients undergoing on-pump CABG, allocated to receive pre-ischemic placebo (5% dextrose) or GIK (40% dextrose, K
+
100 mmol.L
−1
, insulin 70 u.L
−1
; 0.75 mL.kg
−1
.h
−1
) continued for 6 hours after the removal of the aortic cross-clamp (AXC), underwent left ventricular biopsy for analysis of specific mRNAs immediately before AXC, before release of AXC, and 10 minutes after reperfusion (placebo n=24, GIK n=24). GIK or placebo was infused for a mean of 79±21 minutes or 79±18 minutes pre-ischemia respectively. Serial hemodynamic measurements were performed. Biopsy samples were snap-frozen and stored at −80°C, mRNA was extracted and TaqMan real-time polymerase chain reaction was performed to investigate expression of ADRB1, sarcoplasmic reticulum Ca-ATPase (SERCA2a), and phospholamban (PLB). GIK significantly increased cardiac index versus placebo (
P
=0.037). TaqMan reverse-transcriptase polymerase chain reaction showed significantly greater ADRB1 mRNA expression at all time points (4.9-fold, 7.4-fold, and 15.6-fold increase, respectively;
P
<0.001), significantly greater SERCA2a mRNA expression after reperfusion (13.2-fold;
P
<0.001), and increased PLB mRNA expression at pre-ischemia and reperfusion (
P
<0.001 for both time-points) in GIK groups versus placebo.

Conclusions—

The beneficial hemodynamic effects of GIK therapy are associated with increased ADRB1 and SERCA2a mRNA expression. Further work is therefore warranted to investigate these mRNA effects at the protein level.
Indices of Apoptosis Activation After Blood Cardioplegia and Cardiopulmonary Bypass
Authors: Ramlawi Basel , Feng Jun , Mieno Shigetoshi , Szabo Csaba , Zsengeller Zsuzsanna , Clements Richard , Sodha Neel , Boodhwani Munir , Bianchi Cesario , Sellke Frank W.
Published: July 2006

Background—

Cardioplegic arrest (CA) using cold blood cardioplegia (CBC) has been reported to reduce ischemia-reperfusion (IR)-induced myocardial injury via apoptosis. We studied key apoptotic mediators via the caspase-dependent and intrinsic pathways as well as poly(ADP)-ribosylating protein (PARP) activity in myocardial and peripheral tissues after CA and cardiopulmonary bypass (CBP).

Methods and Results—

Right atrial (RA) and skeletal muscle(SM) was harvested from cardiac surgical patients with similar baseline characteristics (N =6) before and after CPB and CBC. Total and modified caspase-3, Bcl-2, Bad, apoptosis-inducing factor (AIF), and PARP were quantified by immunoblotting. Terminal caspase-3 activity was assessed and immunohistochemistry was performed for PARP and AIF. TUNEL staining was used for identification of apoptotic cells. Microarray gene expression analysis was performed using Affymetrix U95 GeneChip. In RA tissue, CA with CBC significantly increased phosphorylation of Bcl-2 (Ser
70
), Bad (Ser
112
) (2.63±0.4 and 1.77±0.3-fold respectively;
P
<0.05), and cleavage of the downstream caspase 3 (1.45±0.1-fold;
P
<0.05). There was no significant change in total protein levels. Also, there was an increase in mature AIF (57 kDa) levels (1.22±0.01-fold;
P
<0.05) and a trend toward nuclear translocation on histological staining. Caspase 3 activity was increased 1.5±0.14-fold (
P
<0.05). The number of apoptotic cells in atrial tissue increased after compared with before CPB/CA using TUNEL staining (1.55±0.66 versus 0.325±0.05%, respectively;
P
=0.03). In contrast, SM samples did not show any of the changes observed in RA tissue after CPB.

Conclusion—

Despite optimal current surgical myocardial protection, we found that CA with CBC induced both programmed cell death and survival signaling in myocardial tissue.
Low-Dose Dobutamine Tissue-Tagged Magnetic Resonance Imaging With 3-Dimensional Strain Analysis Allows Assessment of Myocardial Viability in Patients With Ischemic Cardiomyopathy
Authors: Bree Douglas , Wollmuth Jason R. , Cupps Brian P. , Krock Marc D. , Howells Analyn , Rogers Joseph , Moazami Nader , Pasque Michael K.
Published: July 2006

Background—

Tissue-tagged magnetic resonance imaging (MRI) with 3-dimensional (3D) myocardial strain analysis allows quantitative assessment of myocardial contractility. We assessed the hypothesis that 3D strain determination at rest and with low-dose dobutamine would discriminate between viable and nonviable myocardium in patients with ischemic cardiomyopathy (ICM).

Methods and Results—

MRI with radiofrequency tissue-tagging at rest and with low-dose dobutamine was performed in 16 normal volunteers and 14 patients with ICM. Three-dimensional global and regional circumferential strains (Ecc) were computed for all subjects at rest and with dobutamine. Results were compared with clinically indicated conventional viability studies. Compared with normal volunteers, global left ventricular Ecc was significantly decreased in patients with ICM at rest (−0.15±0.06 versus −0.27±0.03;
P
<0.001) and with dobutamine (−0.17±0.08 versus −0.37±0.10;
P
<0.001). Ecc was significantly decreased in nonviable regions compared with viable segments at rest (−0.08±0.06 versus −0.17±0.10;
P
<0.001) and with dobutamine (−0.07±0.06 versus −0.21±0.11;
P
<0.001). Ecc in viable segments increased significantly in response to dobutamine (
P
=0.04), whereas Ecc did not change in nonviable segments (
P
=0.50). Normal controls (96 segments) had increased Ecc at rest (−0.27±0.07) and with dobutamine (−0.37±0.15) compared with both viable and nonviable regions in ICM patients (
P
<0.001).

Conclusions—

Noninvasive dobutamine tissue-tagged MRI with calculation of 3D strain allows the identification, quantification and display of regionally varying ventricular function. The response of systolic strain to low-dose dobutamine has significant promise in discriminating between viable and nonviable myocardium.
Multislice Computed Tomography Accurately Quantifies Left Atrial Size and Function After the MAZE Procedure
Authors: Yamanaka Kazuo , Fujita Masatoshi , Doi Kazuhiko , Tsuneyoshi Hiroshi , Yamazato Ario , Ueno Katsuya , Zen Eiwa , Komeda Masashi
Published: July 2006

Background—

Although the MAZE procedure allows for the recovery of sinus rhythm and left atrial (LA) mechanical function in the great majority of patients with chronic atrial fibrillation (AF), the effects of MAZE on the precise LA geometry and wall motion remain to be elucidated. We hypothesized that LA size and mechanical function in patients with chronic AF and mitral valvular disease are well restored after MAZE.

Methods and Results—

We studied 14 patients (MAZE group: mean±SD age, 63.9±8.6 years; 8 men and 6 women) who underwent MAZE for chronic AF and mitral valve surgery and 10 patients with sinus rhythm (coronary artery bypass graft [CABG] group: age, 70.0±7.9 years; 5 men and 5 women) who underwent CABG at Takeda Hospital between February 2002 and September 2005. MAZE was conducted by the endocardial application of radiofrequency ablation with a temperature-controlled multipolar radiofrequency catheter. LA volume and booster function were quantitatively evaluated by multislice computed tomography at 17.9±10.0 months (MAZE group) and 15.3±13.6 months (CABG group) postoperatively. All patients with MAZE were free of AF and other atrial arrhythmias during the follow-up period. In the CABG group, LA maximal and minimal volumes and ejection fraction were 109±12 mL, 82±11 mL, and 26±10%, respectively. In the MAZE group, LA maximal volume was 139±17 mL (
P
=0.187 versus CABG), and LA minimal volume was 121±16 mL (
P
=0.082 versus CABG), with an ejection fraction of 15±7% (
P
=0.004 versus CABG). In both groups, all parts of the LA wall contracted toward the geometric center of the LA. The extent of wall motion was significantly worse in the MAZE group compared with the CABG group. In both groups, LA booster function was inversely correlated with LA maximal volume.

Conclusions—

MAZE with radiofrequency ablation is safe and effective for the restoration of sinus rhythm in patients with chronic AF and mitral valve disease. However, chronic AF associated with mitral valve disease deteriorates LA mechanical function diffusely throughout the LA wall. Further studies with the use of multislice computed tomography are needed to sequentially evaluate LA function after MAZE in patients with and without mitral valve surgery.
Lumen Loss in the First Year in Saphenous Vein Grafts Is Predominantly a Result of Negative Remodeling of the Whole Vessel Rather Than a Result of Changes in Wall Thickness
Authors: Lau George T. , Ridley Lloyd J. , Bannon Paul G. , Wong Louise A. , Trieu Joseph , Brieger David B. , Lowe Harry C. , Freedman Ben S. , Kritharides Leonard
Published: July 2006

Background—

The use of saphenous vein grafts (SVG) in coronary artery bypass surgery is established but little is known of SVG remodeling during the first year in vivo.

Methods and Results—

The feasibility of measuring total vessel diameter (lumen plus wall), lumen diameter, and wall thickness by a novel computed tomography (CT) method was established in phantom model tubes (
r
=0.98 for lumen diameter and
r
=0.98 for wall thickness) and in an initial clinical study of 14 patients correlating CT and intravascular ultrasound measurements of SVG (
r
=0.88 for total vessel diameter,
r
=0.85 for lumen diameter and
r
=0.89 for wall thickness). In a separate group of 42 patients (aged 66±10 years; 36 male, 6 female) undergoing coronary artery bypass grafting, SVG total vessel diameter, lumen diameter, and wall thickness were determined prospectively with multi-slice CT angiography at 1 and 12 months postoperatively. Mean total vessel diameter decreased from 5.95±0.83 mm to 5.39±0.87 mm,
P
<0.001 (range, −39% to +8% change). Twenty-six patients (62%) had a decrease of SVG vessel diameter (negative remodeling) >5%. Mean lumen diameter decreased from 3.69±0.66 mm to 3.36±0.68 mm,
P
<0.001, (range, −40 to +11% change). Surprisingly, mean wall thickness decreased from 1.14±0.27 mm to 1.01±0.21 mm (
P
<0.001; range, −48 to +33% change).

Conclusions—

Lumen loss in SVG between postoperative months 1 and 12 is predominantly caused by negative remodeling of the whole vessel rather than to changes in wall thickness. Therapies targeting negative remodeling may be required for optimal maintenance of SVG lumen in the first postoperative year.
Development of a New Method for Endovascular Aortic Repair
Authors: Kajimoto Masaki , Shimono Takatsugu , Hirano Koji , Miyake Yoichiro , Sawada Yasuhiro , Kato Noriyuki , Hirata Hitoshi , Imanaka-Yoshida Kyoko , Nishikawa Masakatsu , Yoshida Toshimichi , Shimpo Hideto , Horiuchi Takashi , Miyamoto Keiichi
Published: July 2006

Background—

Endovascular aortic repair by stent grafts (S/Gs) has been developed as a less invasive treatment for aortic aneurysms. However, some aneurysmal cavities can remain without organization, causing re-expansion. We demonstrated previously that transplantation of a cell combination (myoblasts and fibroblasts) promoted thrombus organization in a rat model. We also developed basic fibroblast growth factor (bFGF) slow-delivery S/Gs coated with elastin and impregnated with bFGF. Here, we evaluated the effects of cell transplantation combined with bFGF slow release on canine thoracic aortic aneurysmal sacs after S/Gs repair.

Methods and Results—

Thoracic aortic aneurysms were surgically created with jugular vein patches in 15 beagles. Myoblasts and fibroblasts of autologous skeletal muscle were isolated and cultured for cell transplantation. The S/Gs had 6 holes and produced endoleaks in the excluded cavities. Collagen gel (gel group, n=5) or a mixture of skeletal myoblasts and fibroblasts with collagen gel (cell group, n=5) were injected into the aneurysmal sacs excluded by the S/Gs. We also studied the effects of combined therapy of bFGF slow-release S/Gs and cell transplantation (hybrid group, n=5). After 14 days, histological analyses revealed that the excluded aneurysmal cavities of the gel group were filled with fresh thrombus, whereas the excluded cavities in the cell-transplanted groups were occupied by organized tissue. The percentages of the organized areas relative to the excluded cavities, evaluated by Masson’s trichrome staining, were 18.1±4.0%, 52.6±4.0%, and 77.1±6.9% in the gel, cell, and hybrid groups, respectively. Collagen fibers had already appeared, and increased numbers of α-smooth muscle actin-positive cells were observed in the hybrid group.

Conclusions—

Cell transplantation accelerated thrombus organization. Moreover, slow release of bFGF enhanced the effects of cell transplantation. Cell transplantation into unorganized spaces may improve the outcomes of endovascular treatments of aortic aneurysms.
Prognostic Significance of Multiple Previous Percutaneous Coronary Interventions in Patients Undergoing Elective Coronary Artery Bypass Surgery
Authors: Thielmann Matthias , Leyh Rainer , Massoudy Parwis , Neuhäuser Markus , Aleksic Ivan , Kamler Markus , Herold Ulf , Piotrowski Jarowit , Jakob Heinz
Published: July 2006

Background—

A possible relationship between increased perioperative risk during coronary artery bypass grafting (CABG) and previous percutaneous coronary intervention (PCI) is debatable. We sought to determine the impact of previous PCI on patient outcome after elective CABG.

Methods and Results—

Between January 2000 and January 2005, 2626 consecutive patients undergoing first-time isolated elective CABG as the primary revascularization procedure (group 1) were evaluated for in-hospital mortality and major adverse cardiac events (MACEs) and were compared with 360 patients after single PCI (group 2) and with 289 patients after multiple PCI sessions (group 3) before elective CABG. Unadjusted univariate and risk-adjusted multivariate logistic-regression analysis revealed previous multiple PCIs to be strongly associated with in-hospital mortality (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.52 to 3.21;
P
<0.001) and MACEs (OR, 2.28; 95% CI, 1.38 to 3.59;
P
<0.001). To control for selection bias, a computed propensity-score matching based on 13 patient characteristics and preoperative risk factors was performed separately comparing group 1 versus 2 and group 1 versus 3. After propensity matching, conditional logistic-regression analysis confirmed previous multiple PCIs to be strongly associated with in-hospital mortality (OR, 3.01; 95% CI, 1.51 to 5.98;
P
<0.0017) and MACEs (OR, 2.31; 95% CI, 1.45 to 3.67;
P
<0.0004).

Conclusions—

In patients with a history of multiple PCI sessions, perioperative risk for in-hospital mortality and MACEs during subsequent elective CABG is increased.
Inflammatory Gene Polymorphisms and Risk of Postoperative Myocardial Infarction After Cardiac Surgery
Authors: Podgoreanu M.V. , White W.D. , Morris R.W. , Mathew J.P. , Stafford-Smith M. , Welsby I.J. , Grocott H.P. , Milano C.A. , Newman M.F. , Schwinn D.A. ,   Perioperative Genetics and Safety Outcomes Study (PEGASUS) Investigative Team
Published: July 2006

Background—

The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery.

Methods and Results—

We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level ≥10× upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted
P
<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (
IL6
−572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (
ICAM1
Lys469Glu; OR, 1.88), and E-selectin (
SELE
98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703).

Conclusions—

Functional genetic variants in cytokine and leukocyte–endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.
Tumor Necrosis Factor Receptor 1 Signaling Resistance in the Female Myocardium During Ischemia
Authors: Wang Meijing , Tsai Ben M. , Crisostomo Paul R. , Meldrum Daniel R.
Published: July 2006

Background—

Tumor necrosis factor-α (TNF) is increased in myocardial tissue after ischemia and reperfusion (I/R). TNF contributes to postischemic myocardial dysfunction and induces proinflammatory signaling, which may be mediated by the 55-kDa TNF receptor (TNFR1). In humans, there is a direct correlation between functional capacity, survival, and circulating TNF levels. Although decreasing the TNF level in animals was beneficial after myocardial ischemia, simply decreasing the bioavailability of TNF in humans with heart failure was not beneficial. This led to the important appreciation that TNF may have beneficial or deleterious effects in the heart, depending on which of its receptors is activated. Females have a lower incidence of heart failure and a higher heart failure survival than males. We hypothesized that TNFR1 signaling resistance occurs in the female myocardium during ischemia.

Methods and Results—

Hearts from male and female TNFR1-knockout and wild-type (WT) mice were subjected to I/R. Female WT mice had better postischemic recovery than did male WT mice, an effect that appeared to be due to TNFR1 signaling resistance in females. Female WT mice had less myocardial depression after TNF infusion despite equivalent TNFR1 expression. Interestingly, TNFR1 ablation improved postischemic myocardial function, decreased activation of p38 mitogen-activated protein kinase, and reduced expression of interleukins-1β and -6 in males but not in females. Furthermore, WT females expressed more of the suppressor of cytokine signaling protein 3 after I/R, which may in part explain TNFR1 signaling resistance in the female myocardium.

Conclusions—

This study demonstrates that sex differences exist in myocardial TNF signaling by TNFR1 after I/R.
Long-Term Outcomes After Valve Replacement for Low-Gradient Aortic Stenosis
Authors: Kulik Alexander , Burwash Ian G. , Kapila Varun , Mesana Thierry G. , Ruel Marc
Published: July 2006

Background—

The long-term outcomes of patients with low-gradient aortic stenosis (LGAS) after aortic valve replacement (AVR) are poorly defined. The purpose of this study was to define the long-term outcomes of LGAS patients after AVR and to evaluate the potential impact of prosthesis–patient mismatch (PPM) in these patients.

Methods and Results—

A cohort of 664 patients undergoing AVR for aortic stenosis after 1990 were followed-up prospectively with annual clinical assessment and echocardiography (total follow-up 3447 patient-years; mean follow-up 5.2±3.3 years). LGAS was defined as an aortic valve area <1.2 cm
2
, a mean transvalvular pressure gradient <40 mm Hg, and a left ventricular (LV) ejection fraction <50%, and was present in 79 patients. Rates and correlates of survival, freedom from congestive heart failure (CHF), and LV mass regression after AVR were determined using multivariate regression methods. Ten-year survival and freedom from CHF after AVR were 72.7±7.5% and 68.2±9.5%, respectively, for patients with LGAS, compared with 89.6±1.8% and 84.1±4.2% for patients without LGAS (hazard ratio [HR] for death and postoperative CHF, 3.1±1.1 and 2.7±0.9, respectively;
P
<0.01). In LGAS patients, PPM, defined as an indexed effective orifice area ≤0.85 cm
2
/m
2
, was independently associated with increased rates of CHF (HR, 3.6±2.2;
P
=0.039), impaired LV mass regression (
P
=0.037), and a trend toward increased late mortality (HR, 3.0±1.9;
P
=0.084).

Conclusions—

Patients with LGAS have worse long-term outcomes after AVR compared with patients without LGAS. PPM adversely affects the long-term outcomes of LGAS patients and should be avoided in this population.
Ventricular Diastolic Stiffness Predicts Perioperative Morbidity and Duration of Pleural Effusions After the Fontan Operation
Authors: Garofalo Cara A. , Cabreriza Santos E. , Quinn T. Alexander , Weinberg Alan D. , Printz Beth F. , Hsu Daphne T. , Quaegebeur Jan M. , Mosca Ralph S. , Spotnitz Henry M.
Published: July 2006

Background—

We validated the clinical relevance of ventricular stiffness by examining surgical morbidity in children with univentricular hearts undergoing Fontan operation. We hypothesized that ventricular stiffness affects Fontan morbidity, particularly duration of pleural effusions.

Methods and Results—

Sixteen children with right ventricular (RV) (n =11) or left ventricular (LV) (n =5) dominance were studied intraoperatively at a median age of 3.3 years (1.8 to 5.1). Transesophageal long-axis echocardiograms and ventricular pressure by micromanometer provided end-diastolic pressure (P) area (A) relations during initiation and conclusion of cardiopulmonary bypass. Curve fitting to the equation P=αe
βA
defined the ventricular stiffness constant, β. Changes in β and clinical correlations were examined. Ventricular stiffness increased after bypass in patients with complete pre-bypass and post-bypass data (n =11,
P
=0.023, mixed models methodology). Pre-bypass β correlated well with duration of chest tube (CT) drainage (
r
=0.90, n =16), net perioperative fluid balance (
r
=0.71, n=14), and length of stay (LOS) (
r
=0.81, n =16). CT duration and LOS also correlated significantly with post-bypass β (
r
=0.77 for both, n=11), but insignificantly with preoperative catheterization pressures.

Conclusions—

Intraoperative β predicts duration of CT drainage, net perioperative fluid balance, and LOS after the Fontan operation. These observations could improve risk stratification and clinical management of children at high-risk undergoing the Fontan operation.
Magnetic Forces Enable Rapid Endothelialization of Synthetic Vascular Grafts
Authors: Pislaru Sorin V. , Harbuzariu Adriana , Agarwal Gautam , Witt AAS CVT LATG Tyra , Gulati Rajiv , Sandhu Nicole P. , Mueske AA Cheryl , Kalra Manju , Simari Robert D. , Sandhu Gurpreet S.
Published: July 2006

Background—

Synthetic vascular grafts cannot be used in small vessels because of graft failure caused by thrombosis and neointima formation. Rapid endothelialization may overcome this limitation. We hypothesized that a magnetic graft would be able to capture and retain endothelial cells labeled with paramagnetic particles.

Methods and Results—

Porcine blood derived endothelial cells were allowed to endocytose superparamagnetic iron oxide microspheres. Cell survival was assessed by trypan blue exclusion and demonstrated a dose-dependent cell survival of 75% to 95%. A flexible magnetic sheet was annealed to the external surface of a knitted Dacron graft. Labeled cells (10
6
/mL) were placed within the graft for 5 minutes. Confocal and electron microscopy confirmed uniform cell capture at the magnetized surface. The effect of shear forces on the adherent cells was evaluated in a flow chamber. The cells remained attached at rates up to 300 mL/min, with cell loss commencing at 400 mL/min. Prototype magnetic grafts were implanted in porcine carotid arteries. Labeled cells were placed within the graft for 10 minutes at the time of implantation. The grafts were evaluated after one day and uniform cell coverage was noted on the magnetized surface. In comparison, relatively few labeled cells were seen attached to a nonmagnetized surface.

Conclusions—

Magnetic forces can be used to rapidly cover a vascular graft with paramagnetically labeled cells. This biophysical interaction is sufficient to retain cells in the presence of blood flow. Applications of this technique may include rapid endothelialization of synthetic vascular grafts and dialysis fistulas.
Effects of Undersized Mitral Annuloplasty on Regional Transmural Left Ventricular Wall Strains and Wall Thickening Mechanisms
Authors: Cheng Allen , Nguyen Tom C. , Malinowski Marcin , Liang David , Daughters George T. , Ingels Neil B. , Miller D. Craig
Published: July 2006

Background—

Undersized mitral annuloplasty, widely used for ischemic and functional mitral regurgitation (MR), has been proposed as an “annular solution to a ventricular problem.” Beyond relief of MR, it is thought to improve global left ventricular (LV) shape, hence potentially reducing myocardial stress and promoting beneficial reverse LV remodeling. We previously observed that undersized annuloplasty inhibited systolic wall thickening at the LV base near the mitral annulus. In this study, we measured the effects of undersized annuloplasty on regional transmural LV wall fiber and sheet strains and wall thickening mechanisms.

Methods and Results—

Nine sheep had transmural radiopaque beadsets surgically inserted into anterobasal and lateral equatorial LV regions, with additional markers silhouetting the LV and mitral annulus. 4-Dimensional marker dynamics were studied with biplane videofluoroscopy before and after tightening an adjustable Paneth-type mitral annuloplasty suture. Transmural circumferential, longitudinal, and radial systolic and remodeling strains in the subepicardium (20% depth), midwall (50%), and subendocardium (80%) in both regions were computed. Fiber and sheet angles from quantitative regional histology allowed transformation of these strains into local fiber (f), sheet (s), and sheet-normal (n) coordinates. Further analysis calculated the transmural contributions of sheet extension (E
ssc
), sheet thickening (E
nnc
), and sheet shear (E
snc
) to systolic wall thickening (E
33
). In the anterobasal region, undersized annuloplasty reduced systolic wall thickening (E
33
) by &50% at all transmural depths by inhibiting: (1) subendocardial systolic fiber shortening (−0.10±0.05 versus −0.04±0.05;
P
<0.05); (2) subepicardial (0.16±0.15 versus 0.09±0.08;
P
<0.05) and subendocardial (0.45±0.40 versus 0.19±0.18;
P
<0.05) systolic sheet thickening; (3) midwall sheet extension (0.22±0.12 versus 0.11±0.06;
P
<0.05); and (4) transmural sheet shear (subepicardium, −0.14±0.07 versus −0.08±0.07; midwall, 0.21±0.12 versus 0.10±0.11; subendocardium, −0.19±0.23 versus −0.11±0.16;
P
<0.05). In the remote lateral equatorial region, fiber-sheet strains and E
33
were unchanged.

Conclusions—

In this acute animal study, undersized annuloplasty inhibited systolic wall thickening in the anterobasal region by reducing subendocardial systolic fiber shortening and laminar sheet wall thickening, but had no effects in a more distant LV region. This suggests that undersized mitral annuloplasty may have potentially deleterious effects on local myocardial mechanics.
Repair of Bicuspid Aortic Valves in Patients With Aortic Regurgitation
Authors: El Khoury Gébrine , Vanoverschelde Jean-Louis , Glineur David , Pierard Frédéric , Verhelst Robert R. , Rubay Jean , Funken Jean-Christophe , Watremez Christine , Astarci Parla , Lacroix Valérie , Poncelet Alain , Noirhomme Philippe
Published: July 2006

Background—

Bicuspid aortic valve regurgitation can be caused by a defect in the valve itself or by dysfunction of one or more components of the aortic root complex. A successful repair thus requires correction of all aspects of the problem simultaneously. We review our experience addressing both the valve and the aortic root when correcting bicuspid valve regurgitation.

Methods and Results—

Between 1996 and 2004, we treated 68 patients for aortic regurgitation. Thirty patients had isolated aortic regurgitation, and 38 had an associated ascending aortic aneurysm. All patients were treated using a standardized and integrated surgical technique, which included resection of the median raphe or leaflet plication, subcommissural annuloplasty, reinforcement of the leaflet free edge, and sinotubular junction plication. In the 38 patients with proximal aortic dilatation, reimplantation or remodeling of the aortic root was performed. Immediate postoperative echocardiography showed grade ≤1 aortic regurgitation in all patients. Three patients nonetheless needed an early re-operation because of recurrent regurgitation. No hospital mortality was observed. At a mean follow-up of 34 months after surgery, all patients were in New York Heart Association (NYHA) class 1 or 2. Two patients needed a re-operation (23 and 92 months, respectively). Echocardiographic follow-up showed no progression of the regurgitation in 58 surviving patients. Four patients progressed to grade 2 regurgitation.

Conclusion—

Our data indicate that regurgitant bicuspid aortic valves, whether alone or in association with a proximal aortic dilatation, can be repaired successfully provided that both the valve and the aortic root problems are treated simultaneously.
Transforming Growth Factor-β1 Modulates Extracellular Matrix Production, Proliferation, and Apoptosis of Endothelial Progenitor Cells in Tissue-Engineering Scaffolds
Authors: Sales Virna L. , Engelmayr George C. , Mettler Bret A. , Johnson John A. , Sacks Michael S. , Mayer John E.
Published: July 2006

Background—

Valvular endothelial cells and circulating endothelial progenitor cells (EPCs) can undergo apparent phenotypic change from endothelial to mesenchymal cell type. Here we investigated whether EPCs can promote extracellular matrix formation in tissue engineering scaffolds in response to transforming growth factor (TGF)-β1.

Method and Results—

Characterized ovine peripheral blood EPCs were seeded onto poly (glycolic acid)/poly (4-hydroxybutyrate) scaffolds for 5 days. After seeding at 2×10
6
cells/cm
2
, scaffolds were incubated for 5 days in a roller bottle, with or without the addition of TGF-β1. After seeding at 15×10
6
cells/cm
2
, scaffolds were incubated for 10 days in a roller bottle with or without the addition of TGF-β1 for the first 5 days. Using immunofluorescence and Western blotting, we demonstrated that EPCs initially exhibit an endothelial phenotype (ie, CD31
+
, von Willebrand factor
+
, and α–smooth muscle actin (SMA)
−
) and can undergo a phenotypic change toward mesenchymal transformation (ie, CD31
+
and α-SMA
+
) in response to TGF-β1. Scanning electron microscopy and histology revealed enhanced tissue formation in EPC-TGF-β1 scaffolds. In both the 10- and 15-day experiments, EPC-TGF-β1 scaffolds exhibited a trend of increased DNA content compared with unstimulated EPC scaffolds. TGF-β1–mediated endothelial to mesenchymal transformation correlated with enhanced expression of laminin and fibronectin within scaffolds evidenced by Western blotting. Strong expression of tropoelastin was observed in response to TGF-β1 equal to that in the unstimulated EPC. In the 15-day experiments, TGF-β1–stimulated scaffolds revealed dramatically enhanced collagen production (types I and III) and incorporated more 5-bromodeoxyuridine and TUNEL staining compared with unstimulated controls.

Conclusions—

Stimulation of EPC-seeded tissue engineering scaffolds with TGF-β1 in vitro resulted in a more organized cellular architecture with glycoprotein, collagen, and elastin synthesis, and thus noninvasively isolated EPCs coupled with the pleiotropic actions of TGF-β1 could offer new strategies to guide tissue formation in engineered cardiac valves.
Environmental Impacts of Products: A Detailed Review of Studies
Authors: Tukker Arnold , Jansen Bart
Published: July 2006

Environmental effects of economic activities are ultimately driven by consumption, via impacts of the production, use, and waste management phases of products and services ultimately consumed. Integrated product policy (IPP) addressing the life‐cycle impacts of products forms an innovative new generation of environmental policy. Yet this policy requires insight into the final consumption expenditures and related products that have the greatest life‐cycle environmental impacts. This review article brings together the conclusions of 11 studies that analyze the life‐cycle impacts of total societal consumption and the relative importance of different final consumption categories. This review addresses in general studies that were included in the project Environmental Impacts of Products (EIPRO) of the European Union (EU), which form the basis of this special issue. Unlike most studies done in the past 25 years on similar topics, the studies reviewed here covered a broad set of environmental impacts beyond just energy use or carbon dioxide (CO2) emissions. The studies differed greatly in basic approach (extrapolating LCA data to impacts of consumption categories versus approaches based on environmentally extended input‐output (EEIO) tables), geographical region, disaggregation of final demand, data inventory used, and method of impact assessment. Nevertheless, across all studies a limited number of priorities emerged. The three main priorities, housing, transport, and food, are responsible for 70% of the environmental impacts in most categories, although covering only 55% of the final expenditure in the 25 countries that currently make up the EU. At a more detailed level, priorities are car and most probably air travel within transport, meat and dairy within food, and building structures, heating, and (electrical) energy‐using products within housing. Expenditures on clothing, communication, health care, and education are considerably less important. Given the very different approaches followed in each of the sources reviewed, this result hence must be regarded as extremely robust. Recommendations are given to harmonize and improve the methodological approaches of such analyses, for instance, with regard to modeling of imports, inclusion of capital goods, and making an explicit distinction between household and government expenditure.
Environmental Impacts of Products:Policy Relevant Information and Data Challenges
Authors: Tukker Arnold , Eder Peter , Suh Sangwon
Published: July 2006

The research and analysis presented in this special issue shows that the same limited number of consumption categories are consistently revealed to be responsible for the largest share of environmental impact: mobility (automobile and air transport), food (meat, poultry, fish, and dairy followed by plant‐based food), and residential energy use in the house (heating, cooling, electrical appliances, and lighting). It appears that differences in impact per euro between the product groupings are relatively limited, so it is essential to reduce the life‐cycle impacts of products as such, rather than to shift expenditures to less impact‐intensive product groupings. Furthermore, the effectiveness of expenditure on material products to improve quality of life leaves much room for improvement. Environmentally extended input‐output (EEIO) tables probably form, in this field, the most appropriate information support tool for priority setting, prospective assessment of options, scenario analysis, and monitoring. A clear benefit would result from integrating the input–output (IO) tables in the report to Eurostat of the 25 individual countries that make up the European Union (EU), with other officially available information on emissions and resources use, into a 60‐sector EEIO table for the EU. This, obviously, would be the first step toward more detailed tables. Three strategies are suggested to realize the additional, desirable detail of 150 sectors or more, each achievable at an increasing time horizon and with increasing effort: (1) developing further the current CEDA EU25 table; (2) building a truly European detailed input–output table accepting the restrictions of existing data gathering procedures; and (3) as (2), but developing new, dedicated data gathering and classification procedures. In all cases, a key issue is harmonizing classification systems for industry sectors, consumer expenditure categories, and product classifications (as in import/export statistics) in such a way that data sets may adequately be linked to input–output tables.
Increasing Minority Research Participation Through Community Organization Outreach
Authors: Alvarez Roger A. , Vasquez Elias , Mayorga Carla C. , Feaster Daniel J. , Mitrani Victoria B.
Published: July 2006

Recruitment is one of the most significant challenges in conducting research with ethnic minority populations. Establishing relationships with organizations that serve ethnic minority communities can facilitate recruitment. To create a successful recruitment process, a strategic plan of action is necessary prior to implementing community outreach efforts. For this study population of women who were HIV+ and recovering from substance abuse disorder, the authors found that establishing trust with community organizations that serve these women allows for a productive referral relationship. Although the majority of women in this study are African American, the authors were particularly challenged in recruiting Hispanic women. This article presents a recruitment process model that has facilitated our recruitment efforts and has helped the authors to organize, document, and evaluate their community out-reach strategies. This model can be adopted and adapted by nurses and other health researchers to enhance engagement of minority populations.
School Design, Site Selection, and the Political Geography of Race in Postwar Philadelphia
Authors: Clapper Michael
Published: July 2006

Through a close exploration of site selection and school design, this article seeks to demonstrate the continued significance of school buildings on the landscape of Philadelphia. By assessing the decisions made by school district bureaucrats in the post–World War II era in light of race, the roots of a separate and unequal school system are revealed.