circulation2011-03-01

Abstract 1 of 7
Congenital Heart Disease
Congenital Heart Defects in Europe
Prevalence and Perinatal Mortality, 2000 to 2005
Helen Dolk, DrPh; Maria Loane, MA; Ester Garne, MD; a European Surveillance of Congenital Anomalies (EUROCAT) Working Group
From the EUROCAT Central Registry, Centre for Maternal, Fetal and Infant Research, Institute of Nursing Research, University of Ulster, UK (H.D., M.L.); and Department of Pediatrics, Hospital Lillebaelt, Kolding, Denmark (E.G.).
Correspondence to Helen Dolk, Professor of Epidemiology and Health Services Research, University of Ulster, Jordanstown Campus, Shore Rd, Co Antrim, BT370QB, Northern Ireland, UK. E-mail h.dolk@ulster.ac.uk.
Background—This study determines the prevalence of Congenital Heart Defects(CHD), diagnosed prenatally or in infancy, and fetal and perinatalmortality associated with CHD in Europe.
Methods and Results—Data were extracted from the European Surveillance of CongenitalAnomalies central database for 29 population-based congenitalanomaly registries in 16 European countries covering 3.3 millionbirths during the period 2000 to 2005. CHD cases (n=26 598)comprised live births, fetal deaths from 20 weeks gestation,and terminations of pregnancy for fetal anomaly (TOPFA). Theaverage total prevalence of CHD was 8.0 per 1000 births, andlive birth prevalence was 7.2 per 1000 births, varying betweencountries. The total prevalence of nonchromosomal CHD was 7.0per 1000 births, of which 3.6% were perinatal deaths, 20% prenatallydiagnosed, and 5.6% TOPFA. Severe nonchromosomal CHD (ie, excludingventricular septal defects, atrial septal defects, and pulmonaryvalve stenosis) occurred in 2.0 per 1000 births, of which 8.1%were perinatal deaths, 40% were prenatally diagnosed, and 14%were TOPFA (TOPFA range between countries 0% to 32%). Live-bornCHD associated with Down syndrome occurred in 0.5 per 1000 births,with >4-fold variation between countries.
Conclusion—Annually in the European Union, we estimate 36 000 childrenare live born with CHD and 3000 who are diagnosed with CHD dieas a TOFPA, late fetal death, or early neonatal death. Investingin primary prevention and pathogenetic research is essentialto reduce this burden, as well as continuing to improve cardiacservices from in utero to adulthood.
Abstract 2 of 7
Epidemiology and Prevention
Low Prevalence of "Ideal Cardiovascular Health" in a Community-Based Population
The Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) Study
Claudia Bambs, MD, MSc; Kevin E. Kip, PhD; Andrea Dinga, MEd, RD, LDN; Suresh R. Mulukutla, MD; Aryan N. Aiyer, MD; Steven E. Reis, MD
From the School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile (C.B.); College of Nursing, University of South Florida, Tampa, FL (K.E.K.); and Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA (A.D., S.R.M., A.N.A., S.E.R.).
Correspondence to Steven Reis, MD, University of Pittsburgh, 3550 Terrace St, Pittsburgh, PA 15261. E-mail sreis@pitt.edu
Background—Cardiovascular health is a new construct defined by the AmericanHeart Association (AHA) as part of its 2020 Impact Goal definition.The applicability of this construct to community-based populationsand the distributions of its components by race and sex havenot been reported.
Methods and Results—The AHA construct of cardiovascular health and the AHA idealhealth behaviors index and ideal health factors index were evaluatedamong 1933 participants (mean age 59 years; 44% blacks; 66%women) in the community-based Heart Strategies Concentratingon Risk Evaluation (Heart SCORE) study. One of 1933 participants(0.1%) met all 7 components of the AHA's definition of idealcardiovascular health. Less than 10% of participants met [img]file:///C:/DOCUME~1/ADMINI~1/LOCALS~1/Temp/msohtml1/01/clip_image001.gif[/img]5 componentsof ideal cardiovascular health in all subgroups (by race, sex,age, and income level). Thirty-nine subjects (2.0%) had all4 components of the ideal health behaviors index and 27 (1.4%)had all 3 components of the ideal health factors index. Blackshad significantly fewer ideal cardiovascular health componentsthan whites (2.0±1.2 versus 2.6±1.4; P<0.001).After adjustment by sex, age, and income level, blacks had 82%lower odds of having [img]file:///C:/DOCUME~1/ADMINI~1/LOCALS~1/Temp/msohtml1/01/clip_image001.gif[/img]5 components of ideal cardiovascular health(odds ratio 0.18, 95% confidence interval, 0.10 to 0.34; P<0.001).No interaction was found between race and sex.
Conclusion—The prevalence of ideal cardiovascular health is extremely lowin a middle-aged community-based study population. Comprehensiveindividual and population-based interventions must be developedto support the attainment of the AHA's 2020 Impact Goal forcardiovascular health.
Abstract 3 of 7
Hypertension
Hypertension, White Matter Hyperintensities, and Concurrent Impairments in Mobility, Cognition, and Mood
The Cardiovascular Health Study
Ihab Hajjar, MD, MS; Lien Quach, MPH, MS; Frances Yang, PhD; Paulo H.M. Chaves, MD, PhD; Anne B. Newman, MD, MPH; Kenneth Mukamal, MD, MPH; Will Longstreth, Jr, MD, MPH; Marco Inzitari, MD, PhD; Lewis A. Lipsitz, MD
From the Institute for Aging Research (I.H., L.Q., L.A.L., F.Y.), Hebrew SeniorLife, Harvard Medical School, Boston, MA (I.H., L.A.L., F.Y., K.M.); Division of Gerontology, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA (I.H., F.Y., K.M., L.A.L.); Center on Aging and Health, Johns Hopkins University, Baltimore, MD (P.H.M.C.); Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA (A.B.N.); Division of Neurology, University of Washington, Seattle, WA (W.L.); Pere Virgili Hospital, Institute on Aging of the Autonomous, University of Barcelona, Barcelona, Spain (M.I.); and Department of Medicine, University of Southern California, Los Angeles, CA (I.H.).
Correspondence to Ihab Hajjar, MD, MS, Assistant Professor of Medicine, Harvard Medical School, Associate Scientist, Institute for Aging Research/Hebrew SeniorLife, Division of Gerontology, Beth Israel Deaconess Medical Center, Boston MA. E-mail ihabhajjar@hrca.harvard.edu
Background—Our objective was to investigate the association between hypertensionand concurrent impairments in mobility, cognition, and mood;the role of brain white matter hyperintensities in mediatingthis association; and the impact of these impairments on disabilityand mortality in elderly hypertensive individuals.
Methods and Results——Blood pressure, gait speed, digit symbol substitutiontest, and the Center for Epidemiological Studies DepressionScale were measured yearly (1992–1999) on 4700 participantsin the Cardiovascular Health Study (age: 74.7, 58% women, 17%blacks, 68% hypertension, 3600 had brain magnetic resonanceimaging in 1992–1993, survival data 1992–2005).Using latent profile analysis at baseline, we found that 498(11%) subjects had concurrent impairments and 3086 (66%) wereintact on all 3 measures. Between 1992 and 1999, 651 (21%) becameimpaired in all 3 domains. Hypertensive individuals were morelikely to be impaired at baseline (odds ratio 1.23, 95% confidenceinterval 1.04 to 1.42, P=0.01) and become impaired during thefollow-up (hazard ratio=1.3, 95% confidence interval 1.02 to1.66, P=0.037). A greater degree of white matter hyperintensitieswas associated with impairments in the 3 domains (P=0.007) andmediated the association with hypertension (P=0.19 for hypertensionafter adjusting for white matter hyperintensities in the model,21% hazard ratio change). Impairments in the 3 domains increasedsubsequent disability with hypertension (P<0.0001). Hypertensionmortality also was increased in those impaired (compared withunimpaired hypertensive individuals: HR=1.10, 95% confidenceinterval 1.04 to 1.17, P=0.004).
Conclusions—Hypertension increases the risk of concurrent impairments inmobility, cognition, and mood, which increases disability andmortality. This association is mediated in part by microvascularbrain injury.
Abstract 4 of 7
Molecular Cardiology
Notch1 in Bone Marrow–Derived Cells Mediates Cardiac Repair After Myocardial Infarction
Yuxin Li, MD, PhD; Yukio Hiroi, MD, PhD; Soeun Ngoy, BS; Ryuji Okamoto, MD, PhD; Kensuke Noma, MD, PhD; Chao-Yung Wang, MD; Hong-Wei Wang, MD, PhD; Qian Zhou, MD; Freddy Radtke, PhD; Ronglih Liao, PhD; James K. Liao, MD
From Vascular Medicine Research (Y.L., Y.H., R.O., K.N., C.W., H.W., Q.Z., J.K.L.) and Department of Medicine (S.N., R.L.), Brigham and Women's Hospital and Harvard Medical School, and Harvard Stem Cell Institute (S.N., R.L.), Boston, MA; Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland (F.R.); and Department of Advanced Cardiovascular Imaging Analysis, Nihon University School of Medicine, Tokyo, Japan (Y.L.).
Correspondence to James K. Liao, MD, Brigham and Women's Hospital, 65 Landsdowne St, Room 275, Cambridge, MA 02139. E-mail jliao@rics.bwh.harvard.edu
Background—The signaling mechanisms that regulate the recruitment of bonemarrow (BM)–derived cells to the injured heart are notwell known. Notch receptors mediate binary cell fate determinationand may regulate the function of BM-derived cells. However,it is not known whether Notch1 signaling in BM-derived cellsmediates cardiac repair after myocardial injury.
Methods and Results—Mice with postnatal cardiac-specific deletion of Notch1 exhibitinfarct size and heart function after ischemic injury that issimilar to that of control mice. However, mice with global hemizygousdeletion of Notch1 (N1^±) developed larger infarct sizeand worsening heart function. When the BM of N1^± micewere transplanted into wild-type (WT) mice, infarct size andheart function were worsened and neovascularization in the infarctborder area was reduced compared with WT mice transplanted withWT BM. In contrast, transplantation of WT BM into N1^± mice lessened the myocardial injury observed in N1^± mice.Indeed, hemizygous deletion of Notch1 in BM-derived cells leadsto decreased recruitment, proliferation, and survival of mesenchymalstem cells (MSC). Compared with WT MSC, injection of N1^± MSC into the infarcted heart leads to increased myocardial injurywhereas injection of MSC overexpressing Notch intracellulardomain leads to decreased infarct size and improved cardiacfunction.
Conclusions—These findings indicate that Notch1 signaling in BM-derivedcells is critical for cardiac repair and suggest that strategiesthat increase Notch1 signaling in BM-derived MSC could havetherapeutic benefits in patients with ischemic heart disease.
Abstract 5 of 7
Resuscitation Science
Is Hypothermia After Cardiac Arrest Effective in Both Shockable and Nonshockable Patients?
Insights From a Large Registry
Florence Dumas, MD; David Grimaldi, MD; Benjamin Zuber, MD; Jér?me Fichet, MD; Julien Charpentier, MD; Frédéric Pène, MD, PhD; Beno?t Vivien, MD, PhD; Olivier Varenne, MD; Pierre Carli, MD, PhD; Xavier Jouven, MD, PhD; Jean-Philippe Empana, MD, PhD; Alain Cariou, MD, PhD
From INSERM U970, Paris Cardiovascular Research Centre, PARCC (F.D., O.V., X.J., J.E., A.C.) UMR-S970 (F.D., O.V., X.J., J.E., A.C.), and Medical School (O.V.), Paris Descartes University; Medical Intensive Care Unit, AP-HP, Cochin Hospital (D.G., B.Z., J.F., J.C., F.P., A.C.); Emergency Department, AP-HP, H?tel Dieu Hospital (F.D.); Department of Cardiology, AP-HP, Cochin Hospital (O.V.); and SAMU 75, AP-HP, Necker Hospital (B.V., P.C.); all in Paris, France.
Correspondence to Alain Cariou, Service de Réanimation Médicale, H?pital Cochin, 27 rue du Faubourg Saint Jacques 75679 Paris cedex 14, France. E-mail alain.cariou@cch.aphp.fr
Background—Although the level of evidence of improvement is significantin cardiac arrest patients resuscitated from a shockable rhythm(ventricular fibrillation or pulseless ventricular tachycardia[VF/VT]), the use of therapeutic mild hypothermia (TMH) is morecontroversial in nonshockable patients (pulseless electric activityor asystole [PEA/asystole]). We therefore assessed the prognosticvalue of hypothermia for neurological outcome at hospital dischargeaccording to first-recorded cardiac rhythm in a large cohort.
Methods and Results—Between January 2000 and December 2009, data from 1145 consecutiveout-of-hospital cardiac arrest patients in whom a successfulresuscitation had been achieved were prospectively collected.The association of TMH with a good neurological outcome at hospitaldischarge (cerebral performance categories level 1 or 2) wasquantified by logistic regression analysis. TMH was inducedin 457/708 patients (65%) in VF/VT and in 261/437 patients (60%)in PEA/asystole. Overall, 342/1145 patients (30%) reached afavorable outcome (cerebral performance categories level 1 or2) at hospital discharge, respectively 274/708 (39%) in VF/VTand 68/437 (16%) in PEA/asystole (P<0.001). After adjustment,in VF/VT patients, TMH was associated with increased odds ofgood neurological outcome (adjusted odds ratio, 1.90; 95% confidenceinterval, 1.18 to 3.06) whereas in PEA/asystole patients, TMHwas not significantly associated with good neurological outcome(adjusted odds ratio, 0.71; 95% confidence interval, 0.37 to1.36).
Conclusions—In this large cohort of cardiac arrest patients, hypothermiawas independently associated with an improved outcome at hospitaldischarge in patients presenting with VF/VT. By contrast, TMHwas not associated with good outcome in nonshockable patients.Further investigations are needed to clarify this lack of efficiencyin PEA/asystole.
Abstract 6 of 7
Valvular Heart Disease
Outcome of Patients With Low-Gradient "Severe" Aortic Stenosis and Preserved Ejection Fraction
Nikolaus Jander, MD^*; Jan Minners, MD, PhD^*; Ingar Holme, PhD; Eva Gerdts, MD, PhD; Kurt Boman, MD, PhD; Philippe Brudi, MD; John B. Chambers, MD; Kenneth Egstrup, MD, PhD; Y. Antero Kes?niemi, MD, PhD; William Malbecq, PhD; Christoph A. Nienaber, MD; Simon Ray, MD; Anne Rosseb?, MD; Terje R. Pedersen, MD, PhD; Terje Skj?rpe, MD, PhD; Ronnie Willenheimer, MD, PhD; Kristian Wachtell, MD, PhD; Franz-Josef Neumann, MD; Christa Gohlke-B?rwolf, MD
From the Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (N.J., J.M., F.N., C.G.-B.); Oslo University Hospital, Ullev?l Centre of Preventive Medicine, Oslo, Norway (I.H.); Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway (E.G.); Department of Medicine, Skellefte?, Institution of Public Health and Clinical Medicine, Ume? University, Ume?, Sweden (K.B.); Merck/Schering-Plough Pharmaceuticals, Inc, Whitehouse Station, NJ (P.B.); Cardiothoracic Centre, Guys-St Thomas Hospital Trust, London, UK (J.B.C.); Department of Medicine, Svendborg Hospital, Svendborg, Denmark (K.E.); Department of Internal Medicine and Biocenter Oulu, University of Oulu, Finland (Y.A.K.); MSD Europe, Inc, Brussels, Belgium (W.M.); Medizinische Klinik I, Universit?tsklinikum Rostock, Germany (C.A.N.); Department of Cardiology, University Hospitals of South Manchester, South Manchester, UK (S.R.); Division of Cardiology, Oslo University Hospital, Aker, Norway (A.R.); University of Oslo, Ullev?l, Centre of Preventive Medicine, Oslo, Norway (T.R.P.); Section of Cardiology, St Olav's Hospital, Trondheim, Norway (T.S.); Heart Health Group and Lund University, Malm?, Sweden (R.W.); and Department of Cardiology, Rigshospitalet, Copenhagen, Denmark (K.W.)
Correspondence to Nikolaus Jander, MD, Herz-Zentrum Bad Krozingen, Suedring 15, 79189 Bad Krozingen, Germany. nikolaus.jander@herzzentrum.de
Background—Retrospective studies have suggested that patients with a lowtransvalvular gradient in the presence of an aortic valve area<1.0 cm² and normal ejection fraction may represent a subgroupwith an advanced stage of aortic valve disease, reduced strokevolume, and poor prognosis requiring early surgery. We thereforeevaluated the outcome of patients with low-gradient "severe"stenosis (defined as aortic valve area <1.0 cm² and meangradient [img]file:///C:/DOCUME~1/ADMINI~1/LOCALS~1/Temp/msohtml1/01/clip_image002.gif[/img]40 mm Hg) in the prospective Simvastatin and Ezetimibein Aortic Stenosis (SEAS) study.
Methods and Results—Outcome in patients with low-gradient "severe" aortic stenosiswas compared with outcome in patients with moderate stenosis(aortic valve area 1.0 to 1.5 cm²; mean gradient 25 to 40 mmHg). The primary end point of aortic valve events included deathfrom cardiovascular causes, aortic valve replacement, and heartfailure due to aortic stenosis. Secondary end points were majorcardiovascular events and cardiovascular death. In 1525 asymptomaticpatients (mean age, 67±10 years; ejection fraction, [img]file:///C:/DOCUME~1/ADMINI~1/LOCALS~1/Temp/msohtml1/01/clip_image001.gif[/img]55%),baseline echocardiography revealed low-gradient severe stenosisin 435 patients (29%) and moderate stenosis in 184 (12%). Leftventricular mass was lower in patients with low-gradient severestenosis than in those with moderate stenosis (182±64versus 212±68 g; P<0.01). During 46 months of follow-up,aortic valve events occurred in 48.5% versus 44.6%, respectively(P=0.37; major cardiovascular events, 50.9% versus 48.5%, P=0.58;cardiovascular death, 7.8% versus 4.9%, P=0.19). Low-gradientsevere stenosis patients with reduced stroke volume index ([img]file:///C:/DOCUME~1/ADMINI~1/LOCALS~1/Temp/msohtml1/01/clip_image002.gif[/img]35mL/m²; n=223) had aortic valve events comparable to those inpatients with normal stroke volume index (46.2% versus 50.9%;P=0.53).
Conclusions—Patients with low-gradient "severe" aortic stenosis and normalejection fraction have an outcome similar to that in patientswith moderate stenosis.
Abstract 7 of 7
Valvular Heart Disease
Comparison of the Structure of the Aortic Valve and Ascending Aorta in Adults Having Aortic Valve Replacement for Aortic Stenosis Versus for Pure Aortic Regurgitation and Resection of the Ascending Aorta for Aneurysm
William Clifford Roberts, MD; Travis James Vowels; Jong Mi Ko, BA; Giovanni Filardo, PhD, MPH; Robert Frederick Hebeler, Jr, MD; Albert Carl Henry, MD; Gregory John Matter, MD; Baron Lloyd Hamman, MD
From the Baylor Heart and Vascular Institute (W.C.R., T.J.V., J.M.K.) and the Departments of Pathology (W.C.R.), Internal Medicine (Division of Cardiology) (W.C.R.), and Cardiothoracic Surgery (R.F.H., A.C.H., G.J.M., B.L.H.), and Institute for Health Care Research and Improvement (G.F.), Baylor Health Care System, Baylor University Medical Center, Dallas, TX; and the Department of Statistical Science (G.F.), Southern Methodist University, Dallas, TX.
Correspondence to William C. Roberts, MD, Baylor Heart and Vascular Institute, Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246. E-mail wc.roberts@baylorhealth.edu
Background—There is debate concerning whether an aneurysmal ascending aortashould be replaced when associated with a dysfunctioning aorticvalve that is to be replaced. To examine this issue, we dividedthe patients by type of aortic valve dysfunction—eitheraortic stenosis (AS) or pure aortic regurgitation (AR)—somethingnot previously undertaken.
Methods and Results—Of 122 patients with ascending aortic aneurysm (unassociatedwith aortitis or acute dissection), the aortic valve was congenitallymalformed (unicuspid or bicuspid) in 58 (98%) of the 59 AS patients,and in 38 (60%) of the 63 pure AR patients. Ascending aorticmedial elastic fiber loss (EFL) (graded 0 to 4+) was zero or1+ in 53 (90%) of the AS patients, in 20 (53%) of the 38 ARpatients with bicuspid valves, and in all 12 AR patients withtricuspid valves unassociated with the Marfan syndrome. An unadjustedanalysis showed that, among the 96 patients with congenitallymalformed valves, the 38 AR patients had a significantly higherlikelihood of 2+ to 4+ EFL than the 58 AS patients (crude oddsratio: 8.78; 95% confidence interval: 2.95, 28.13).
Conclusions—These data strongly suggest that the type of aortic valve dysfunction—ASversus pure AR—is very helpful in predicting loss of aorticmedial elastic fibers in patients with ascending aortic aneurysmsand aortic valve disease.