Circulation 2010年9月14日Vol. 122, No. 11增刊1 （摘要，全文免费）---续

http://circ.ahajournals.org/content/vol122/11_suppl_1

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Abstract 20 of 34 (Circulation. 2010;122:S216-S223.)
© 2010 American Heart Association, Inc.

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Surgery for Congenital Heart Disease

Major Adverse Cardiac and Cerebrovascular Events After the Ross Procedure
A Report From the German-Dutch Ross Registry
Hans-H. Sievers, MD; Ulrich Stierle, MD; Efstratios I. Charitos, MD; Thorsten Hanke, MD; Martin Misfeld, MD, PhD; J.F. Matthias Bechtel, MD; Armin Gorski, MD; Ulrich F.W. Franke, MD; Bernhard Graf, MD; Derek R. Robinson, MA, MSc, DPhil, CStat; Ad J.J.C. Bogers, MD; Ali Dodge-Khatami, MD; Juergen O. Boehm, MD; Joachim G. Rein, MD; Cornelius A. Botha, MD; Ruediger Lange, MD; Juergen Hoerer, MD; Anton Moritz, MD; Thorsten Wahlers, MD, PhD; Martin Breuer, MD; Katharina Ferrari-Kuehne, MD; Roland Hetzer, MD, PhD; Michael Huebler, MD; Gerhard Ziemer, MD; Johanna J.M. Takkenberg, MD, PhD; Wolfgang Hemmer, MD, on behalf of the German-Dutch Ross Registry
From University of Luebeck (H.H.S., U.S., E.I.C., T.H., M.M., J.F.M.B., A.G.), Department of Cardiac and Thoracic Vascular Surgery, Luebeck, Germany (Registry Site); Sana Herzchirurgische Klinik (J.O.B., J.G.R., W.H.), Stuttgart, Germany; Robert-Bosch-Hospital (U.F.W.F.), Stuttgart, Germany; Helios Kliniken Schwerin (B.G.), Schwerin, Germany; Department of Mathematics (D.R.R.), School of Mathematical and Physical Sciences, University of Sussex, Brighton, United Kingdom; Department of Cardio-Thoracic Surgery (A.J.J.C.B., J.J.M.T.), Erasmus University Medical Center, Rotterdam, The Netherlands; University Heart Center Hamburg (A.D.-K.), Hamburg, Germany; Herzzentrum Bodensee (C.A.B.), Konstanz, Germany, German Heart Center (R.L., J.H.), Munich, Germany; Johann-Wolfgang-Goethe University (A.M.), Frankfurt/Main, Germany; University of Cologne (T.W.), Cologne, Germany; Friedrich-Schiller University (M.B., K.F.-K.), Jena, Germany; German Heart Center (R.H., M.H.), Berlin, Germany; Eberhard-Karls-University (G.Z.), Tuebingen, Germany.

Correspondence to Efstratios I. Charitos, MD, University of Luebeck, Department of Cardiac and Thoracic Vascular Surgery, Ratzeburger Allee 160, 23538 Luebeck, Germany. E-mail efstratios.charitos@gmail.com

Background—The purpose of the study is to report major cardiac and cerebrovascular events after the Ross procedure in the large adult and pediatric population of the German-Dutch Ross registry. These data could provide an additional basis for discussions among physicians and a source of information for patients.

Methods and Results—One thousand six hundred twenty patients (1420 adults; 1211 male; mean age, 39.2±16.2 years) underwent a Ross procedure between 1988 and 2008. Follow-up was performed on an annual basis (median, 6.2 years; 10 747 patient-years). Early and late mortality were 1.2% (n=19) and 3.6% (n=58; 0.54%/patient-year), respectively. Ninety-three patients underwent 99 reinterventions on the autograft (0.92%/patient-year); 78 reinterventions in 63 patients on the pulmonary conduit were performed (0.73%/patient-year). Freedom from autograft or pulmonary conduit reoperation was 98.2%, 95.1%, and 89% at 1, 5, and 10 years, respectively. Preoperative aortic regurgitation and the root replacement technique without surgical autograft reinforcement were associated with a greater hazard for autograft reoperation. Major internal or external bleeding occurred in 17 (0.15%/patient-year), and a total of 38 patients had composite end point of thrombosis, embolism, or bleeding (0.35%/patient-year). Late endocarditis with medical (n=16) or surgical treatment (n=29) was observed in 38 patients (0.38%/patient-year). Freedom from any valve-related event was 94.9% at 1 year, 90.7% at 5 years, and 82.5% at 10 years.

Conclusions—Although longer follow-up of patients who undergo Ross operation is needed, the present series confirms that the autograft procedure is a valid option to treat aortic valve disease in selected patients. The nonreinforced full root technique and preoperative aortic regurgitation are predictors for autograft failure and warrant further consideration.

Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00708409.

Key Words: registries • surgery • valves

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Abstract 21 of 34 (Circulation. 2010;122:S224-S233.)
© 2010 American Heart Association, Inc.

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Surgery for Congenital Heart Disease

Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC)
A Multicenter Placebo-Controlled Randomized Trial: Age Analysis
Michael A. Portman, MD; April Slee, MS; Aaron K. Olson, MD; Gordon Cohen, MD, PhD; Tom Karl, MD; Elizabeth Tong, PhD; Laura Hastings, MD; Hitendra Patel, MD; Olaf Reinhartz, MD; Antonio R. Mott, MD; Richard Mainwaring, MD; Justin Linam, MA; Sara Danzi, PhD, for the TRICC Investigators
From Seattle Children’s Hospital and University of Washington (M.A.P., A.K.O., G.C.), Seattle, Wash; University of California San Francisco (T.K.), San Francisco, Calif; Children’s Hospital of Los Angeles (L.H.), Los Angeles, Calif; Children’s Hospital and Research Center Oakland (H.P., O.R.), Oakland, Calif; Baylor College of Medicine (A.R.M.), Houston, Tex; Sutter Medical Center (R.M), Sacramento, Calif; Axio Research (A.S.), Seattle, Wash; North Shore University Health Systems (S.D.), Manhasset, NY. *Other TRICC Investigators are listed in Acknowledgments.

Correspondence to Michael A. Portman, Seattle Children’s Research Institute, 1900 9th Ave, Seattle, WA 98101. E-mail Michael.portman@seattlechildrens.org

Background—Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome.

Methods and Results—The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7–22) for placebo and 20 hours (CI, 16–45) for Triostat and (hazard ratio, 0.60; P=0.0220).

Conclusions—T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months.

Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417.

Key Words: cardiopulmonary bypass • congenital heart surgery • thyroid hormone

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Abstract 22 of 34 (Circulation. 2010;122:S234-S240.)
© 2010 American Heart Association, Inc.

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Surgery for Congenital Heart Disease

Sex Differences in Mortality in Children Undergoing Congenital Heart Disease Surgery
A United States Population–Based Study
Ariane Marelli, MD; Kimberlee Gauvreau, ScD; Mike Landzberg, MD; Kathy Jenkins, MD, MPH
From the McGill Adult Unit for Congenital Heart Disease (MAUDE Unit) (A.M.), Montreal, Canada; and Children’s Hospital Boston (K.G., M.L., K.J.), Mass.

Correspondence to Dr Ariane J. Marelli, Director, McGill Adult Unit for Congenital Heart Disease, McGill University Health Centre, 687 Pine Ave West, Room H4-33, Montreal, Quebec, Canada, H3A 1A1. E-mail ariane.marelli@mcgill.ca

Background—The changing demographics of the adult congenital heart disease (CHD) population requires an understanding of the factors that impact patient survival to adulthood. We sought to investigate sex differences in CHD surgical mortality in children.

Methods and Results—Children <18 years old hospitalized for CHD surgery were identified using the Kids’ Inpatient Database in 2000, 2003, and 2006. Demographic, diagnostic, and procedural variables were grouped according to RACHS-1 (Risk Adjustment for Congenital Heart Surgery) method. Logistic regression was used to determine the odds ratio of death in females versus males adjusting for RACHS-1 risk category, age, prematurity, major noncardiac anomalies, and multiple procedures. Analyses were stratified by RACHS-1 risk categories and age. Of 33 848 hospitalizations for CHD surgery, 54.7% were in males. Males were more likely than females to have CHD surgery in infancy, high-risk CHD surgery, and multiple CHD procedures. Females had more major noncardiac structural anomalies and more low-risk procedures. However, the adjusted risk of in-hospital death was higher in females (odds ratio, 1.21; 95% confidence interval, 1.08 to 1.36) on account of the subgroup with high-risk surgeries who were <1 year of age (odds ratio, 1.39; 95% confidence interval, 1.16 to 1.67).

Conclusions—In this large US population study, more male children underwent CHD surgery and had high-risk procedures. Female infants who had high-risk procedures were at higher risk for death, but this accounted for a small proportion of females and is therefore unlikely to have a major impact on the changing demographics in adults in CHD.

Key Words: heart defects • congenital • mortality • sex differences

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Abstract 23 of 34 (Circulation. 2010;122:S241-S248.)
© 2010 American Heart Association, Inc.

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Surgery for Congenital Heart Disease

Rapid-Response Extracorporeal Membrane Oxygenation to Support Cardiopulmonary Resuscitation in Children With Cardiac Disease
David A. Kane, MD; Ravi R. Thiagarajan, MBBS, MPH; David Wypij, PhD; Mark A. Scheurer, MD; Francis Fynn-Thompson, MD; Sitaram Emani, MD; Pedro J. del Nido, MD; Peter Betit, RRT; Peter C. Laussen, MBBS
From Department of Cardiology (D.A.K., R.R.T., D.W., M.A.S., P.B., P.C.L.), Children’s Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, Mass; Department of Biostatistics (D.W.), Harvard School of Public Health, Boston, Mass; Department of Cardiac Surgery (F.F.-T., S.E., P.J.d.N.), Children’s Hospital Boston, Boston, Mass and Department of Surgery, Harvard Medical School, Boston, Mass.

Correspondence to David Kane, MD, Children’s Hospital Boston, Department of Cardiology, 300 Longwood Avenue, Boston, MA 02115. E-mail david.kane@cardio.chboston.org

Background—Survival of children with in-hospital cardiac arrest that does not respond to conventional cardiopulmonary resuscitation (CPR) is poor. We report on survival and early neurological outcomes of children with heart disease supported with rapid-response extracorporeal membrane oxygenation (ECMO) to aid cardiopulmonary resuscitation (ECPR).

Methods and Results—Children with heart disease supported with ECPR were identified from our ECMO database. Demographic, CPR, and ECMO details associated with mortality were evaluated using multivariable logistic regression. Pediatric overall performance category and pediatric cerebral performance category scores were assigned to ECPR survivors to assess neurological outcomes. There were 180 ECPR runs in 172 patients. Eighty-eight patients (51%) survived to discharge. Survival in patients who underwent ECPR after cardiac surgery (54%) did not differ from nonsurgical patients (46%). Survival did not vary by cardiac diagnosis and CPR duration did not differ between survivors and nonsurvivors. Factors associated with mortality included noncardiac structural or chromosomal abnormalities (OR, 3.2; 95% CI, 1.3–7.9), use of blood-primed ECMO circuit (OR, 7.1; 95% CI, 1.4–36), and arterial pH <7.00 after ECMO deployment (OR, 6.0; 95% CI, 2.1–17.4). Development of end-organ injury on ECMO and longer ECMO duration were associated with increased mortality. Of pediatric overall performance category/pediatric cerebral performance category scores assigned to survivors, 75% had scores 2, indicating no to mild neurological injury.

Conclusions—ECPR may promote survival in children with cardiac disease experiencing cardiac arrest unresponsive to conventional CPR with favorable early neurological outcomes. CPR duration was not associated with mortality, whereas patients with metabolic acidosis and noncardiac structural or chromosomal anomalies had higher mortality.

Key Words: cardiopulmonary resuscitation • congenital heart defects • extracorporeal circulation • pediatrics

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Abstract 24 of 34 (Circulation. 2010;122:S48-S52.)
© 2010 American Heart Association, Inc.

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Surgery for Coronary Artery Disease

Five-Year Follow-Up of a Randomized Comparison Between Off-Pump and On-Pump Stable Multivessel Coronary Artery Bypass Grafting. The MASS III Trial
Whady Hueb, MD, PhD; Neuza H. Lopes, MD, PhD; Alexandre C. Pereira, MD, PhD; Alexandre C. Hueb, MD, PhD; Paulo Rogério Soares, MD, PhD; Desidério Favarato, MD, PhD; Ricardo D'Oliveira Vieira, MD; Eduardo Gomes Lima, MD; Cibele Larrosa Garzillo, MD, PhD; Felipe da Silva Paulitch, MD; Luiz A.M. César, MD, PhD; Bernard J. Gersh, MB, ChB, DPhil; José A.F. Ramires, MD, PhD
From the Heart Institute of the University of São Paulo, São Paulo, Brazil (W.H., H.N.L., A.C.P., A.C.H., P.R.S., D.F., R.D.V., E.G.L., C.L.G., F.d.S.P., L.A.M.C., J.A.F.R.); Mayo Clinic, Rochester, MN (B.J.G.).

Correspondence to Whady Hueb, MD, PhD, Ave Dr Enéas de Carvalho Aguiar 44, AB 114 Cerqueira César, São Paulo 05403-000, Brazil. E-mail whady.hueb@incor.usp.br or mass@incor.usp.br

Background—Coronary artery bypass graft surgery with cardiopulmonary bypass is a safe, routine procedure. Nevertheless, significant morbidity remains, mostly because of the body’s response to the nonphysiological nature of cardiopulmonary bypass. Few data are available on the effects of off-pump coronary artery bypass graft surgery (OPCAB) on cardiac events and long-term clinical outcomes.

Methods and Results—In a single-center randomized trial, 308 patients undergoing coronary artery bypass graft surgery were randomly assigned: 155 to OPCAB and 153 to on-pump CAB (ONCAB). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. After 5-year follow-up, the primary composite end point was not different between groups (hazard ratio 0.71, 95% CI 0.41 to 1.22; P=0.21). A statistical difference was found between OPCAB and ONCAB groups in the duration of surgery (240±65 versus 300±87.5 minutes; P<0.001), in the length of ICU stay (19.5±17.8 versus 43±17.0 hours; P<0.001), time to extubation (4.6±6.8 versus 9.3±5.7 hours; P<0.001), hospital stay (6±2 versus 9±2 days; P<0.001), higher incidence of atrial fibrillation (35 versus 4% of patients; P<0.001), and blood requirements (31 versus 61% of patients; P<0.001), respectively. The number of grafts per patient was higher in the ONCAB than the OPCAB group (2.97 versus 2.49 grafts/patient; P<0.001).

Conclusions—No difference was found between groups in the primary composite end point at 5-years follow-up. Although OPCAB surgery was related to a lower number of grafts and higher episodes of atrial fibrillation, it had no significant implications related to long-term outcomes.

Clinical Trial Registration—URL: http://www.controlled-trials.com. Unique identifier: ISRCTN66068876.

Key Words: cardiopulmonary bypass • coronary artery surgery • ischemic heart disease • coronary heart disease

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Abstract 25 of 34 (Circulation. 2010;122:S53-S59.)
© 2010 American Heart Association, Inc.

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Surgery for Coronary Artery Disease

Remote Ischemic Preconditioning in Human Coronary Artery Bypass Surgery
From Promise to Disappointment?
Ishtiaq A. Rahman, MRCS; Jorge G. Mascaro, MD, FRCS; Rick P. Steeds, MD, FRCP; Michael P. Frenneaux, MD, FRCP; Peter Nightingale, PhD; Peter Gosling, PhD, FRCPath; Peter Townsend, FRCA; John N. Townend, MD, FRCP; David Green, FRCA; Robert S. Bonser, MD, FRCP, FRCS
From the Department of Cardiothoracic Surgery (I.A.R., J.G.M., R.S.B.) and Department of Cardiology (R.P.S., J.N.T.), University Hospital Birmingham NHS Trust, Birmingham, United Kingdom; the Department of Cardiovascular Medicine (M.P.F., R.S.B.), University of Birmingham, Birmingham, United Kingdom; Wellcome Trust Clinical Research Facility (P.N.), Birmingham, United Kingdom; and the Department of Clinical Biochemistry (P.G.) and Department of Anesthetics (P.T., D.G.), University Hospital Birmingham NHS Trust, Birmingham, United Kingdom.

Correspondence to Professor Robert S. Bonser, Department of Cardiothoracic Surgery, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, B15 2TH, UK. E-mail robert.bonser@uhb.nhs.uk

Background—We assessed whether remote ischemic preconditioning (RIPC) improves myocardial, renal, and lung protection after on-pump coronary surgery.

Methods and Results—This was a single-center, prospective, randomized (1:1), placebo-controlled trial. Patients, investigators, anesthetists, surgeons, and critical care teams were blinded to group allocation. Subjects received RIPC (or placebo) stimuli (x3 upper limb (or dummy arm), 5-minute cycles of 200 mm Hg cuff inflation/deflation) before aortic clamping. Anesthesia, perfusion, cardioplegia, and surgical techniques were standardized. The primary end point was 48-hour area under the curve (AUC) troponin T (cTnT) release. Secondary end points were 6-hour and peak cTnT, ECG changes, cardiac index, inotrope and vasoconstrictor use, renal dysfunction, and lung injury. Hospital survival was 99.4%. Comparing placebo and RIPC, median (interquartile range) AUC 48-hour cTnT (ng/mL–1/48 h–1); 28 (19, 39) versus 30 (22, 38), 6-hour cTnT (ng/mL–1); 0.93(0.59, 1.35) versus 1.01(0.72, 1.43), peak cTnT (ng/mL–1); 1.02 (0.74, 1.44) versus 1.04 (0.78, 1.51), de novo left bundle-branch block (4% versus 0%) and Q waves (5.3% versus 5.5%), serial cardiac indices, intraaortic balloon pump usage (8.5% versus 7.5%), inotrope (39% versus 50%) and vasoconstrictor usage (66% versus 64%) were not different. Dialysis requirement (1.2% versus 3.8%), peak creatinine (median [interquartile range], 1.2 mg/dL–1 (1.1, 1.4) versus 1.2 (1.0, 1.4)), and AUC urinary albumin-creatinine ratios 69 (40, 112) versus 58 (32, 85) were not different. Intubation times; median (interquartile range), 937 minutes(766, 1402) versus 895(675, 1180), 6-hour; 278 (210, 338) versus 270 (218, 323) and 12-hour pO2:FiO2 ratios 255 (195, 323) versus 263 (210, 308) were similar.

Conclusions—In contrast to prior smaller studies, RIPC did not reduce troponin release, improve hemodynamics, or enhance renal or lung protection.

Clinical Trial Registration—URL: http://www.ukcrn.org.uk. Unique identifier: 4659.

Key Words: coronary disease • surgery • coronary artery bypass • preconditioning

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Abstract 26 of 34 (Circulation. 2010;122:S60-S65.)
© 2010 American Heart Association, Inc.

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Surgery for Coronary Artery Disease

Chromosome 9p21 Variant Predicts Mortality After Coronary Artery Bypass Graft Surgery
Jochen D. Muehlschlegel, MD, MMSc; Kuang-Yu Liu, PhD; Tjörvi E. Perry, MD, MMSc; Amanda A. Fox, MD; Charles D. Collard, MD; Stanton K. Shernan, MD; Simon C. Body, MBChB, MPH, for the CABG Genomics Investigators
From Department of Anesthesiology, Perioperative, and Pain Medicine (J.D.M., K.-Y.L., T.E.P., A.A.F., S.K.S., S.C.B.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Baylor College of Medicine (C.D.C.), Division of Cardiovascular Anesthesia at the Texas Heart Institute, Saint Luke’s Episcopal Hospital, Houston, Tex.

Correspondence to Jochen D. Muehlschlegel, MD, Department of Anesthesiology, Perioperative and Pain Medicine, CWN L1, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail jmuehlschlegel@partners.org

Background—Recent genome-wide association studies have identified several chromosome 9p21 single nucleotide polymorphisms associated with coronary artery disease and myocardial infarction in nonsurgical populations. We have recently demonstrated an independent association between these 9p21 variants and perioperative myocardial injury after isolated primary coronary artery bypass graft (CABG) surgery. This study investigated the association of a 9p21 variant with mortality in patients after CABG surgery and its prognostic value to improve the EuroSCORE.

Methods and Results—In a 2-center, prospective, observational study of 846 white primary CABG surgery patients, we genotyped rs10116277, the 9p21 variant with the strongest association to perioperative myocardial injury in our cohort. To estimate the utility of rs10116277 for predicting all-cause mortality within 5 years after surgery, a Cox proportional hazard model was constructed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) while adjusting for demographics and clinical covariates.

The homozygote minor allele of rs10116277 was associated with significantly increased risk of all-cause mortality even after adjusting for other clinical predictors of mortality in a Cox proportional hazards model (HR, 1.7; 95% CI, 1.1–2.7; P=0.026). Addition of rs10116277 to the logistic EuroSCORE also significantly improved model prediction for mortality (HR, 1.82; 95% CI, 1.15–2.88; P=0.01).

Conclusion—The 9p21 variant rs10116277 is independently associated with all-cause mortality after primary CABG surgery in whites and significantly improves the predictive value of the logistic EuroSCORE.

Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00281164.

Key Words: cardiopulmonary bypass • genetics • mortality

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Abstract 27 of 34 (Circulation. 2010;122:S66-S73.)
© 2010 American Heart Association, Inc.

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Surgery for Coronary Artery Disease

Preoperative Atorvastatin Treatment in CABG Patients Rapidly Improves Vein Graft Redox State by Inhibition of Rac1 and NADPH-Oxidase Activity
Charalambos Antoniades, MD; Constantinos Bakogiannis, MD; Dimitris Tousoulis, MD, PhD, FACC; Svetlana Reilly, MD, PhD; Mei-Hua Zhang, PhD; Andreas Paschalis, MD; Alexios S. Antonopoulos, MD; Michael Demosthenous, MD; Antigoni Miliou, MSc; Costas Psarros, BSc; Kyriakoula Marinou, MD; Nikolaos Sfyras, MD; George Economopoulos, MD; Barbara Casadei, MD, DPhil, FRCP; Keith M. Channon, MD, FRCP; Christodoulos Stefanadis, MD, FACC, FESC
From the Department of Cardiovascular Medicine (C.A., S.R., M.-H.Z., B.C., K.M.C.), University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; First Department of Cardiology (C.A., C.B., D.T., A.P., A.S.A., M.D., A.M., C.P., K.M., C.S.), University of Athens, Hippokration Hospital, Greece; and Department of Cardiac Surgery (A.P., N.S., G.E.), Hippokration Hospital, Athens, Greece.

Correspondence to Charalambos Antoniades, MD, PhD, Department of Cardiovascular Medicine, West Wing Level 6, University of Oxford, John Radcliffe Hospital OX3 9DU, Oxford, United Kingdom. E-mail antoniad@well.ox.ac.uk

Background—Statins improve clinical outcome of patients with atherosclerosis, but their perioperative role in patients undergoing coronary artery bypass grafting (CABG) is unclear. We hypothesized that short-term treatment with atorvastatin before CABG would improve the redox state in saphenous vein grafts (SVGs), independently of low-density lipoprotein cholesterol (LDL)-lowering.

Methods and Results—In a randomized, double-blind controlled trial, 42 statin-naïve patients undergoing elective CABG received atorvastatin 40 mg/d or placebo for 3 days before surgery. Circulating inflammatory markers and malondialdehyde (MDA) were measured before and after treatment. SVG segments were used to determine vascular superoxide (O2·–) and Rac1 activation. For ex vivo studies, SVG segments from 24 patients were incubated for 6 hours with atorvastatin 0, 5, or 50 µmol/L. Oral atorvastatin reduced vascular basal and NADPH-stimulated O2·– in SVGs (P<0.05 for all versus placebo) and reduced plasma MDA (P<0.05), independently of LDL-lowering and of changes in inflammatory markers. In SVGs exposed to atorvastatin ex vivo, without exposure to LDL, basal and NADPH-stimulated O2·– were significantly reduced (P<0.01 for both concentrations versus 0 µmol/L) in association with a striking reduction in Rac1 activation and 1 membrane-bound Rac1 and p67phox subunit. The antioxidant effects of atorvastatin were reversed by mevalonate, implying a dependence on vascular HMG-CoA reductase inhibition.

Conclusions—Short-term treatment with atorvastatin 40 mg/d before CABG improves redox state in SVGs, by inhibiting vascular Rac1-mediated activation of NADPH-oxidase. These novel findings suggest that statin therapy should be maintained or initiated in patients undergoing CABG, independently of LDL levels.

Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01013103.

Key Words: statins • malondialdehyde • oxidative stress • inflammation • CRP • NADPH-oxidase • superoxide • coronary bypass grafting • Rac1

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Abstract 28 of 34 (Circulation. 2010;122:S3-S9.)
© 2010 American Heart Association, Inc.

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Surgery for Valvular Heart Disease

Mechanism of Beneficial Effects of Restrictive Mitral Annuloplasty in Patients With Dilated Cardiomyopathy and Functional Mitral Regurgitation
Koji Takeda, MD; Kazuhiro Taniguchi, MD; Yasuhiro Shudo, MD; Satoshi Kainuma, MD; Seiki Hamada, MD; Hajime Matsue, MD; Goro Matsumiya, MD; Yoshiki Sawa, MD
From the Department of Cardiovascular Surgery (K.T., Y.S., S.K., H.M., G.M., Y.S.) and the Department of Radiology (S.H.), Osaka University Graduate School of Medicine, Osaka, Japan; and the Department of Cardiovascular Surgery (K.T.), Japan Labor Health and Welfare Organization Osaka Rosai Hospital, Sakai, Japan.

Correspondence to Yoshiki Sawa, MD, 565-0871, 2-2 Yamadaoka, Suita, Osaka, Japan. E-mail sawa@surg1.med.osaka-u.ac.jp

Background—Restrictive mitral annuloplasty (RMA) often leads to reverse left ventricular (LV) remodeling in patients with advanced cardiomyopathy and functional mitral regurgitation. However, the mechanism responsible for its favorable effects on LV ejection performance has been poorly understood. We evaluated systolic wall stress using cineangiographic multidetector computed tomography (MDCT) and our developed software system to assess stress-shortening relations before and after RMA.

Methods and Results—Twenty-four patients with dilated cardiomyopathy underwent 64-row MDCT before and 2 months after RMA. All patients underwent stringent downsizing annuloplasty with a semirigid complete ring. Reconstructed images were used to calculate LV end-diastolic index (EDVI) and end-systolic volume index (ESVI), LV ejection fraction, and regional and global end-systolic wall stress (ESS). After RMA, LVEDVI and LVESVI decreased from 151±52 to 131±53 mL/m2 (P=0.0001) and from 114±48 to 92±50 mL/m2 (P=0.0001), respectively. Global ESS decreased from 157±43 to 139±50 kdyne/cm2 (P=0.01), and LV ejection fraction improved from 27±8.0 to 33±13% (P=0.0007). There were significant correlations between change in LVEDVI and LVESVI (r=0.88, P<0.0001) and change in LVESVI and global ESS (r=0.68, P=0.0002). Moreover, the magnitude of increase in LV ejection fraction significantly correlated with the degree of reduction in global ESS (r=–0.61, P=0.002). Patients without significant reverse LV remodeling had significantly higher preoperative and postoperative global ESS than those with it.

Conclusions—Our study suggests that decrease in afterload after reduction in volume overload was responsible for postoperative reverse LV remodeling process after RMA.

Key Words: mitral valve • cardiomyopathy • annuloplasty • wall stress

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Abstract 29 of 34 (Circulation. 2010;122:S10-S16.)
© 2010 American Heart Association, Inc.

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Surgery for Valvular Heart Disease

Long-Term Clinical and Hemodynamic Performance of the Hancock II Versus the Perimount Aortic Bioprostheses
Vincent Chan, MD, MPH; Alexander Kulik, MD, MPH; Anthony Tran, BSc; Paul Hendry, MD; Roy Masters, MD; Thierry G. Mesana, MD, PhD; Marc Ruel, MD, MPH
From Division of Cardiac Surgery (V.C., A.K., A.T., P.H., R.M., T.G.M., M.R.) and Department of Epidemiology and Community Medicine (M.R.), University of Ottawa, Ottawa, Ontario, Canada.

Correspondence to Marc Ruel, University of Ottawa Heart Institute, 3403-40 Ruskin Street, Ottawa, Ontario, Canada, K1Y 4W7. E-mail mruel@ottawaheart.ca

Background—The Medtronic Hancock II and the Carpentier-Edwards Perimount are among the world’s most commonly used aortic bioprostheses. However, a direct comparison of their clinical performance is lacking. To minimize biases inherent to between-center comparisons, we examined these prostheses within a large, contemporary, single-center cohort.

Methods and Results—Between 1990 and 2007, 1659 patients (mean age, 73.1±9.3 years) underwent aortic valve replacement with either the Hancock II (N=1021) or the Perimount (N=638). Patients were prospectively followed-up with serial clinic visits and echocardiograms for up to 16 years (mean, 5.0±3.3 years). There was no significant difference in aortic root size preoperatively (P=0.7). Aortic root enlargement was more commonly performed with the Perimount (P<0.001), and the manufacturer valve size of the implanted prosthesis was larger with the Hancock II (P<0.001). Postoperatively, peak and mean transprosthesis gradients were higher for the Hancock II (32.7±0.7 and 16.0±0.3 mm Hg, respectively) than for the Perimount (24.9±0.7 and 13.4±0.4 mm Hg, respectively; P<0.001). However, no difference in left ventricular mass regression was observed at late follow-up (P=0.9). Unadjusted 10-year survival was 59.4%±2.4% for the Hancock II and 70.2%±3.8% for the Perimount (P=0.07). Multivariable predictors of survival did not include prosthesis type (P=0.2).

Conclusions—For the same manufacturer valve size, the Perimount is larger, which may warrant enlarging the aortic root more often, and it is associated with better hemodynamics than the Hancock II. These differences do not impact survival or left ventricular mass regression, and the long-term clinical performances of the Hancock II and Perimount bioprostheses are equivalent.

Key Words: echocardiography • surgery • survival • valves

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Abstract 30 of 34 (Circulation. 2010;122:S17-S22.)
© 2010 American Heart Association, Inc.

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Surgery for Valvular Heart Disease

Impact of Early Surgery on Embolic Events in Patients With Infective Endocarditis
Dae-Hee Kim, MD, PhD; Duk-Hyun Kang, MD, PhD; Myung-Zoon Lee, MD; Sung-Cheol Yun, PhD; Yong-Jin Kim, MD, PhD; Jong-Min Song, MD, PhD; Jae-Kwan Song, MD, PhD; Jae-Won Lee, MD, PhD; Dae-Won Sohn, MD, PhD
From the Division of Cardiology (D.-H. Kim, D.-H. Kang, M.-Z.L., J.-M.S., J.-K.S.), Cardiac Surgery (J.-W.L.), Biostatistics (S.-C.Y.), Asan Medical Center, College of Medicine, University of Ulsan; and Cardiovascular Center (Y.-J.K., D.-W.S.), Seoul National University Hospital, Department of Internal Medicine, Seoul National University College of Medicine, Korea.

Correspondence to Duk-Hyun Kang, MD, PhD, Professor of Medicine, Division of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, 388-1, Poongnap-dong, Songpa-ku, Seoul, Korea 138-736. E-mail dhkang@amc.seoul.kr

Background—Surgical indications to prevent systemic embolism in infective endocarditis (IE) remain controversial. We sought to compare clinical outcomes of early surgery with conventional treatment in IE patients with embolic indications only.

Methods and Results—From 1998 to 2006, we prospectively enrolled 132 consecutive patients (86 men; age, 49±17 years) with definite IE. Patients were included if they had a left-sided native valve endocarditis with vegetation. The choice of early surgery or conventional treatment was at the discretion of attending physician. Early surgery was performed on 64 patients (OP group) within 7 days of diagnosis, and conventional management was chosen for 68 patients (CONV group). The OP group had larger vegetations and a higher percentage of patients with severe valvular disease (88% versus 62%, P=0.001). During initial hospitalization, there were no embolic events and 2 in-hospital deaths in the OP group and 14 embolic events and 2 in-hospital deaths in the CONV group. During a median follow-up of 1402 days, there were 2 cardiovascular deaths, 2 embolic events, and 1 recurrence of IE in the CONV group, and 1 cardiovascular death and 2 embolic events in the OP group. The 5-year event-free survival rate was significantly higher in the OP group (93±3%) than in the CONV group (73±5%, P=0.0016). For 44 propensity score–matched pairs, the OP group had a lower event rate (hazard ratio, 0.18; P=0.007).

Conclusions—Compared with conventional treatment, an early surgery strategy is associated with improved clinical outcomes by effectively decreasing systemic embolism in patients with IE.

Key Words: infective endocarditis • vegetation • embolism • heart valve surgery

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Abstract 31 of 34 (Circulation. 2010;122:S23-S28.)
© 2010 American Heart Association, Inc.

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Surgery for Valvular Heart Disease

Regression of Myocardial Hypertrophy After Aortic Valve Replacement
Faster in Women?
George Petrov, MD; Vera Regitz-Zagrosek, MD; Elke Lehmkuhl, MD; Thomas Krabatsch, MD; Anne Dunkel, MSc; Michael Dandel, MD; Elke Dworatzek, PhD; Shokoufeh Mahmoodzadeh, PhD; Carola Schubert, PhD; Eva Becher, PhD; Hannah Hampl; Roland Hetzer, MD
From the Deutsches Herzzentrum Berlin (G.P., V.R.-Z., E.L., T.K., M.D., R.H.), Berlin, Germany; Institute of Gender in Medicine and Center for Cardiovascular Research (G.P., V.R.-Z., E.L., A.D., E.D., S.M., C.S., E.B., H.H.), Charité Universitaetsmedizin Berlin, Berlin, Germany.

Correspondence to Vera Regitz-Zagrosek, Institute of Gender in Medicine, Charité Universitaetsmedizin Berlin, Hessische Straße 3-4, D-10115 Berlin, Germany. E-mail vera.regitz-zagrosek@charite.de

Background—In patients with aortic stenosis, pressure overload induces cardiac hypertrophy and fibrosis. Female sex and estrogens influence cardiac remodeling and fibrosis in animal models and in men. Sex differences and their molecular mechanisms in hypertrophy regression after aortic valve replacement have not yet been studied.

Methods and Results—We prospectively obtained preoperative and early postoperative echocardiography in 92 patients, 53 women and 39 men, undergoing aortic valve replacement for isolated aortic stenosis. We analyzed in a subgroup of 10 patients matrix gene expression in left ventricular (LV) biopsies. In addition, we determined the effect of 17β-estradiol on collagen synthesis in isolated rat cardiac fibroblasts. Preoperatively, women and men had similar ejection fraction. Similar percentages of women and men had increased LV diameters (37% and 38%). Women more frequently exhibited LV hypertrophy than men (women: 86%; men: 56%; P<0.01). Postoperatively, increased LV diameters persisted in 34% of men but only in 12% of women (P<0.023). LV hypertrophy reversed more frequently in women than in men, leading to a similar prevalence of LV hypertrophy after surgery (women: 45%; men: 36%). In surgical biopsies, men had significantly higher collagen I and III and matrix metalloproteinase 2 gene expression than women. In isolated rat cardiac fibroblasts, 17β-estradiol significantly increased collagen I and III gene expressions in male cells but decreased it in female cells.

Conclusion—Women adapt to pressure overload differently from men. Less fibrosis before surgery may enable faster regression after surgery.

Key Words: hypertrophy • remodeling • sex • aortic valve stenosis • estrogen

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Abstract 32 of 34 (Circulation. 2010;122:S29-S36.)
© 2010 American Heart Association, Inc.

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Surgery for Valvular Heart Disease

Assessment of Changes in Mitral Valve Configuration With Multidetector Computed Tomography
Impact of Papillary Muscle Imbrication and Ring Annuloplasty
Yasuhiro Shudo, MD; Goro Matsumiya, MD, PhD; Taichi Sakaguchi, MD, PhD; Shigeru Miyagawa, MD, PhD; Yasushi Yoshikawa, MD, PhD; Takashi Yamauchi, MD, PhD; Koji Takeda, MD; Shunsuke Saito, MD; Satoshi Nakatani, MD, PhD; Kazuhiro Taniguchi, MD, PhD; Hironori Izutani, MD, PhD; Yoshiki Sawa, MD, PhD
From the Department of Cardiovascular Surgery (Y. Shudo, G.M., T.S., S.M., Y.Y., K. Takeda, S.S., Y. Sawa), Osaka University Graduate School of Medicine, Suita, Osaka, Japan; the Division of Functional Diagnostics (S.N.), Department of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; the Department of Cardiovascular Surgery (K. Taniguchi), Japan Labor Health and Welfare Organization, Osaka Rosai Hospital, Sakai, Osaka, Japan; and the Department of Organ Regenerative Surgery (H.I.), Ehime University School of Medicine, Ehime, Japan.

Correspondence to Yoshiki Sawa, MD, PhD, 2-2 Yamadaoka, Suita, Osaka, Japan, Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. E-mail sawa@surg1.med.osaka-u.ac.jp

Background—The optimal surgical procedures in functional mitral regurgitation remain controversial. We applied papillary muscle imbrication (PMI) combined with undersized mitral annuloplasty (UMAP). Multidetector computed tomography (MDCT) provides images of different phases of the cardiac cycle, allowing an assessment of the geometry. In the present study, we evaluated the mitral valve configuration and subvalvular apparatus before and after UMAP and/or PMI using MDCT imaging.

Methods and Results—We studied 26 patients with functional mitral regurgitation (3+ to 4+) with an ejection fraction 35% who underwent diagnostic MDCT examinations before and early after the operation. Of these, 15 underwent UMAP and PMI (UMAP+PMI group) and 11 underwent UMAP (UMAP group). The annular anteroposterior diameter, tenting height, tenting area, and interpapillary muscle distance at end-systole were quantified. The annular anteroposterior diameter, tenting height, and tenting area were significantly decreased after the operation in both groups. Whereas the average change in annular anteroposterior diameter, tenting area, and interpapillary muscle distance did not differ between the 2 groups, the average change in tenting height was greater in the UMAP+PMI group than in the UMAP group (5.1±1.3 versus 3.8±2.3 mm, P=0.036). There was a significant correlation between the change in interpapillary muscle distance and the change in tenting height in the UMAP+PMI group (r=0.788, P=0.0005).

Conclusions—Our results examined with MDCT indicated that UMAP combined with PMI improved leaflet tethering compared with UMAP, reflecting differences in the effects of the surgical procedures used, and suggested that concomitant PMI might be beneficial in some cases.

Key Words: mitral valve • cardiomyopathy • structure • valves • computed tomography

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Abstract 33 of 34 (Circulation. 2010;122:S37-S42.)
© 2010 American Heart Association, Inc.

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Surgery for Valvular Heart Disease

Correlates and Causes of Death in Patients With Severe Symptomatic Aortic Stenosis Who Are Not Eligible to Participate in a Clinical Trial of Transcatheter Aortic Valve Implantation
Itsik Ben-Dor, MD; Augusto D. Pichard, MD; Manuel A. Gonzalez, MD; Gaby Weissman, MD; Yanlin Li, MD; Steven A. Goldstein, MD; Petros Okubagzi, MD; Asmir I. Syed, MD; Gabriel Maluenda, MD; Sara D. Collins, MD; Cedric Delhaye, MD; Kohei Wakabayashi, MD; Michael A. Gaglia, Jr, MD; Rebecca Torguson, MPH; Zhenyi Xue, MS; Lowell F. Satler, MD; William O. Suddath, MD; Kenneth M. Kent, MD, PhD; Joseph Lindsay, MD; Ron Waksman, MD
From the Division of Cardiology, Washington Hospital Center, Washington, DC.

Correspondence to Ron Waksman, Washington Hospital Center, 110 Irving St, NW, Suite 4B-1, Washington, DC 20010. E-mail ron.waksman@medstar.net

Background—Transcatheter aortic valve implantation is currently being evaluated in patients with severe aortic stenosis who are considered high-risk surgical candidates. This study aimed to detect incidences, causes, and correlates of mortality in patients ineligible to participate in transcatheter aortic valve implantation studies.

Methods and Results—From April 2007 to July 2009, a cohort of 362 patients with severe aortic stenosis were screened and did not meet the inclusion/exclusion criteria necessary to participate in a transcatheter aortic valve implantation trial. These patients were classified into 2 groups: group 1 (medical): 274 (75.7%): 97 (35.4%) treated medically and 177 (64.6%) treated with balloon aortic valvuloplasty; and group 2 (surgical): 88 (24.3%). The medical/balloon aortic valvuloplasty group had significantly higher clinical risk compared with the surgical group, with significantly higher Society of Thoracic Surgeons score (12.8±7.0 versus 8.5±5.1; P<0.001) and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (42.4±22.8 versus 24.4±18.1; P<0.001). The medical/balloon aortic valvuloplasty group had a higher New York Heart Association functional class, incidence of renal failure, and lower ejection fraction. During median follow-up of 377.5 days, mortality in the medical/balloon aortic valvuloplasty group was 102 (37.2%), and during median follow-up of 386 days, mortality in the surgical group was 19 (21.5%). Multivariable adjustment analysis identified renal failure (hazard ratio [HR]: 5.60), New York Heart Association class IV (HR: 5.88), and aortic systolic pressure (HR: 0.99) as independent correlates for mortality in the medical group, whereas renal failure (HR: 7.45), Society of Thoracic Surgeons score (STS; HR: 1.09) and logistic EuroSCORE (HR: 1.45) were correlates of mortality in the in the surgical group.

Conclusion—Patients with severe symptomatic aortic stenosis not included in transcatheter aortic valve implantation trials do poorly and have extremely high mortality rates, especially in nonsurgical groups, and loss of quality of life in surgical groups.

Key Words: aortic stenosis • transcatheter aortic valve • outcome

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Abstract 34 of 34 (Circulation. 2010;122:S43-S47.)
© 2010 American Heart Association, Inc.

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Surgery for Valvular Heart Disease

Prognostic Implications of Mitral Regurgitation in Patients With Severe Aortic Regurgitation
Ramdas G. Pai, MD; Padmini Varadarajan, MD
From the Department of Cardiology (R.G.P., P.V.), Loma Linda University Medical Center, Loma Linda, Calif.

Correspondence to Ramdas G. Pai, MD, Division of Cardiology, 11234 Anderson St, Room 4414, Loma Linda University Medical Center, Loma Linda, CA 92354. E-mail ramdaspai@yahoo.com; rpai@llu.edu

Background—Mitral regurgitation (MR) is common in those with severe aortic regurgitation (AR) and can predispose to atrial fibrillation, heart failure, and a need for mitral valve surgery during aortic valve replacement (AVR). However, little data exist as to its clinical and prognostic implications.

Methods and Results—Search of our echocardiographic data base between 1993 and 2007 yielded 756 patients with severe AR. with comprehensive clinical data from chart review and mortality data from National Death Index. Mortality was analyzed as a function of MR severity. Effect of AVR and concomitant mitral valve repair were investigated. Patient characteristics were age, 61±17 years; female sex, 41%; and ejection fraction, 54±19%. MR grade 2+ was present in 343 (45%) patients: 2+ in 152 (20%), 3+ in 93 (12%), and 4+ in 98 (13%). There was a progressive decrease in survival with each grade of MR (P<0.0001). Performance of AVR was associated with a better survival in those with 3 or 4+ MR (P=0.02). In addition, concomitant mitral valve repair in these patients resulted in a better survival (hazard ratio, 0.29; P=0.02).

Conclusions—MR is common in patients with severe AR, with 3 or 4+ MR occurring in a quarter of these patients. It is an independent predictor of reduced survival. Performance of AVR and concomitant mitral valve repair is associated with a better survival. Development of MR should serve as an indication for AVR even in asymptomatic patients.

Key Words: aortic regurgitation • aortic valve • aortic valve replacement • left ventricular dysfunction • survival