circulation2010-12-14
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Abstract 1 of 8
Arrhythmia/Electrophysiology
Marked Variability in Susceptibility to Ventricular Fibrillation in an Experimental Commotio Cordis Model
Alawi A. Alsheikh-Ali, MD, MS; Christopher Madias, MD; Stacey Supran, MA; Mark S. Link, MD
From the Cardiac Arrhythmia Center, Division of Cardiology (C.M., M.S.L.), and Clinical Care Research Division (S.S.), Tufts Medical Center, Boston, Mass; and Institute of Cardiac Sciences, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates (A.A.A.-A.).
Correspondence to Mark S. Link, MD, Cardiac Arrhythmia Center, Division of Cardiology, Tufts Medical Center, 800 Washington St, Box 197, Boston, MA 02111. E-mail mlink@tuftsmedicalcenter.org
Background— Precordial blows in sports and daily activities can trigger ventricular fibrillation (VF) (commotio cordis). Whereas chest wall blows are common, commotio cordis is rare. Although factors such as timing, location, orientation, and energy of impact are critically important, we also hypothesize that there is individual susceptibility to commotio cordis. Using our model of commotio cordis, we evaluated individual animal susceptibility to VF induction and assessed animal characteristics that might be involved.
Methods and Results— This retrospective analysis included 139 juvenile swine (weight, 8 to 54 kg) that were anesthetized and placed prone in a sling to receive chest wall strikes with a ball propelled at 30 to 40 mph. Each animal received a minimum of 4 impacts directly over the cardiac silhouette, all timed to a narrow vulnerable window during cardiac repolarization. Of 1274 total impacts, 360 impacts (28%) resulted in VF. There was wide variability in individual animal susceptibility to VF. In 38 animals, none of the impacts resulted in VF (range, 4 to 18 impacts per animal). The majority of animals (91; 65%) were induced into VF with <30% of the strikes. In fact, only 19 animals (14%) had >50% occurrence of VF with chest wall impacts, and only 7 (5%) had >80% occurrence of chest impacts that induced VF. In the animal-based analysis, individual correlates of VF included animal weight, mean impact velocity, mean left ventricular pressure generated by the blow, mean QRS duration, mean QTc, and QTc variability. In multivariable analysis, mean left ventricular pressure generated by the blow, mean QRS duration, and QTc variability remained significant correlates of risk, and number of impacts gained statistical significance such that animals with more impacts were less susceptible to VF.
Conclusions— Swine display a wide range of individual vulnerability to VF triggered by chest wall impact, with a distinct minority being uniquely susceptible. Mild abnormalities in cardiac depolarization and repolarization might underlie this susceptibility. Such individual susceptibility may also be present in humans and contribute to the rarity of commotio cordis.
Abstract 2 of 8
Coronary Heart Disease
High Levels of Systemic Myeloperoxidase Are Associated With Coronary Plaque Erosion in Patients With Acute Coronary Syndromes
A Clinicopathological Study
Giuseppe Ferrante, MD, PhD; Masataka Nakano, MD; Francesco Prati, MD; Giampaolo Niccoli, MD, PhD; Maria T. Mallus, MD, PhD; Vito Ramazzotti, MD; Rocco A. Montone, MD; Frank D. Kolodgie, PhD; Renu Virmani, MD; Filippo Crea, MD, PhD
From the Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (G.F., G.N., R.A.M., F.C.); Cardiovascular Pathology Institute, Gaithersburg, Md (M.N., F.D.K., R.V.); Interventional Cardiology, San Giovanni Hospital, Rome, Italy (F.P., M.T.M., V.R.); and CLI Foundation, Rome, Italy (F.P.).
Correspondence to Filippo Crea, MD, PhD, Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy. E-mail filippo.crea@rm.unicatt.it
Background— Systemic levels of myeloperoxidase predict prognosis in patients with acute coronary syndromes and are considered a marker of plaque vulnerability. It is not known whether myeloperoxidase is associated with different coronary morphologies (ie, rupture or erosion of the culprit lesion) in patients with acute coronary syndrome.
Methods and Results— Twenty-five consecutive patients (aged 67±11 years; 15 men [60%]; 13 [52%] with non–ST-segment elevation acute coronary syndrome and 12 [48%] with acute ST-segment elevation myocardial infarction) were enrolled. Optical coherence tomography classified the culprit lesion as ruptured in 18 (72%) or eroded in 7 patients (28%) and detected intraluminal thrombus in 89% of ruptured plaques and 100% of eroded plaques. Baseline systemic levels of serum myeloperoxidase were significantly higher in patients with an eroded plaque than in those with a ruptured plaque (median, 2500 ng/mL; 25th to 75th percentile, 1415 to 2920 versus median, 707 ng/mL; 25th to 75th percentile, 312 to 943; P=0.001), whereas C-reactive protein levels did not differ significantly (median, 11.3 mg/L; 25th to 75th percentile, 1.3 to 28.5 versus median, 3.9 mg/L; 25th to 75th percentile, 1.3 to 17.8; P=0.76, respectively). In addition, the density of myeloperoxidase-positive cells within thrombi overlying plaques in postmortem coronary specimens retrieved from sudden coronary death victims was significantly higher in lesions with erosion (n=11) than ruptures (n=11) (median, 1584; 25th to 75th percentile, 1088 to 2135 cells/mm2 versus median, 579; 25th to 75th percentile, 442 to 760 cells/mm2; P=0.0012).
Conclusions— Systemic myeloperoxidase levels are significantly elevated in patients with acute coronary syndrome presenting with eroded culprit plaque compared with patients presenting with ruptured culprit plaque. Consistently, in postmortem coronary specimens, luminal thrombi superimposed on eroded plaques contain a higher density of myeloperoxidase-positive cells than thrombi superimposed on ruptured plaques. This study supports the concept that elevations in selective inflammatory biomarkers reflect specific acute complications of coronary atherosclerosis.
Abstract 3 of 8
Epidemiology and Prevention
Influence of Age on Associations Between Childhood Risk Factors and Carotid Intima-Media Thickness in Adulthood
The Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium
Markus Juonala, MD,, PhD*; Costan G. Magnussen, PhD*; Alison Venn, PhD; Terence Dwyer, MD,, MPH; Trudy L. Burns, MPH,, PhD; Patricia H. Davis, MD; Wei Chen, MD,, PhD; Sathanur R. Srinivasan, PhD; Stephen R. Daniels, MD,, PhD; Mika Khnen, MD,, PhD; Tomi Laitinen, MD,, PhD; Leena Taittonen, MD,, PhD; Gerald S. Berenson, MD; Jorma S.A. Viikari, MD,, PhD; Olli T. Raitakari, MD,, PhD
From the Research Centre of Applied and Preventive Cardiovascular Medicine (M.J., C.G.M., O.T.R.) and the Departments of Clinical Physiology (O.T.R.) and Medicine (M.J., J.S.A.V.), University of Turku and Turku University Hospital, Turku, Finland; Menzies Research Institute (C.G.M., A.V.), University of Tasmania, Hobart, Australia; Murdoch Children's Research Institute (C.G.M., T.D.), Melbourne, Australia; Department of Epidemiology, College of Public Health, and Department of Neurology, Carver College of Medicine, University of Iowa (T.L.B., P.H.D.), Iowa City, Iowa; Department of Epidemiology, Tulane Center for Cardiovascular Health (W.C., S.R.S., G.S.B.), Tulane University School of Public Health and Tropical Medicine, New Orleans, La; Department of Pediatrics, University of Colorado Denver and Health Science Center (S.R.D.), Aurora, Colo; Department of Clinical Physiology, Tampere University Hospital and University of Tampere (M.K.), Tampere, Finland; Department of Clinical Physiology, Kuopio University Hospital (T.L.), Kuopio, Finland; and Department of Pediatrics, Vaasa Central Hospital, Vaasa, Finland and Department of Pediatrics, University of Oulu (L.T.), Oulu, Finland.
Correspondence to Markus Juonala, Department of Medicine, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland. E-mail mataju@utu.fi
Background— Atherosclerosis has its roots in childhood. Therefore, defining the age when childhood risk exposure begins to relate to adult atherosclerosis may have implications for pediatric cardiovascular disease prevention and provide insights about the early determinants of atherosclerosis development. The aim of this study was to investigate the influence of age on the associations between childhood risk factors and carotid artery intima-media thickness, a marker of subclinical atherosclerosis.
Methods and Results— We used data for 4380 members of 4 prospective cohorts—Cardiovascular Risk in Young Finns Study (Finland), Childhood Determinants of Adult Health study (Australia), Bogalusa Heart Study (United States), and Muscatine Study (United States)—that have collected cardiovascular risk factor data from childhood (age 3 to 18 years) and performed intima-media thickness measurements in adulthood (age 20 to 45 years). The number of childhood risk factors (high [highest quintile] total cholesterol, triglycerides, blood pressure, and body mass index) was predictive of elevated intima-media thickness (highest decile) on the basis of risk factors measured at age 9 years (odds ratio [95% confidence interval] 1.37 [1.16 to 1.61], P=0.0003), 12 years (1.48 [1.28 to 1.72], P<0.0001), 15 years (1.56 [1.36 to 1.78], P<0.0001), and 18 years (1.57 [1.31 to 1.87], P<0.0001). The associations with risk factors measured at age 3 years (1.17 [0.80 to 1.71], P=0.42) and 6 years (1.20 [0.96 to 1.51], P=0.13) were weaker and nonsignificant.
Conclusions— Our analyses from 4 longitudinal cohorts showed that the strength of the associations between childhood risk factors and carotid intima-media thickness is dependent on childhood age. On the basis of these data, risk factor measurements obtained at or after 9 years of age are predictive of subclinical atherosclerosis in adulthood.
Abstract 4 of 8
Epidemiology and Prevention
Lifetime Fruit and Vegetable Consumption and Arterial Pulse Wave Velocity in Adulthood
The Cardiovascular Risk in Young Finns Study
Heikki Aatola, MD; Teemu Koivistoinen, MD, MSc; Nina Hutri-K?h?nen, MD, PhD; Markus Juonala, MD, PhD; Vera Mikkil?, PhD; Terho Lehtim?ki, MD, PhD; Jorma S.A. Viikari, MD, PhD; Olli T. Raitakari, MD, PhD; Mika K?h?nen, MD, PhD
From the Departments of Clinical Physiology (H.A., T.K., M.K.), Pediatrics (N.H.-K.), and Clinical Chemistry (T.L.), University of Tampere and Tampere University Hospital, Tampere, Finland; Departments of Medicine (M.J., J.S.A.V.) and Clinical Physiology (O.T.R.) and Research Centre of Applied and Preventive Cardiovascular Medicine (M.J., O.T.R.), University of Turku and Turku University Hospital, Turku, Finland; and Division of Nutrition, University of Helsinki, Helsinki, Finland (V.M.).
Correspondence to Mika K?h?nen, MD, PhD, Department of Clinical Physiology, Tampere University Hospital, PO Box 2000, FI-33521 Tampere, Finland. E-mail mika.kahonen@uta.fi
Background— The relationships between childhood lifestyle risk factors and adulthood pulse wave velocity (PWV) have not been reported. We studied whether childhood and adulthood lifestyle risk factors are associated with PWV assessed in adulthood.
Methods and Results— The study cohort comprised 1622 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (1980; aged 3 to 18 years) with lifestyle risk factor data available since childhood. Arterial PWV was measured in 2007 by whole-body impedance cardiography device. Vegetable consumption in childhood was inversely associated with adulthood PWV (β=–0.06, P=0.02), and this association remained significant (β=–0.07, P=0.004) when adjusted for traditional risk factors (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, body mass index, and smoking). Vegetable consumption was also an independent predictor of PWV in adulthood when adjusted for lifestyle or traditional risk factors (β=–0.08, P=0.002 and β=–0.07, P=0.0007, respectively). Persistently high consumption of both fruits and vegetables from childhood to adulthood was associated with lower PWV compared with persistently low consumption (P=0.03 for both). The number of lifestyle risk factors (the lowest quintile for vegetable consumption, fruit consumption, physical activity, and smoking) in childhood was directly associated with PWV in adulthood (P=0.001). This association remained significant when adjusted for the number of lifestyle risk factors in adulthood (P=0.003).
Conclusions— These findings suggest that lifetime lifestyle risk factors, with low consumption of fruits and vegetables in particular, are related to arterial stiffness in young adulthood.
Abstract 5 of 8
Hypertension
Inhibition and Genetic Ablation of the B7/CD28 T-Cell Costimulation Axis Prevents Experimental Hypertension
Antony Vinh, PhD; Wei Chen, PhD; Yelena Blinder, MD; Daiana Weiss, PhD; W. Robert Taylor, MD, PhD; J?rg J. Goronzy, MD, PhD; Cornelia M. Weyand, MD, PhD; David G. Harrison, MD, PhD; Tomasz J. Guzik, MD, PhD
From the Division of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta Veteran Administration Hospital (A.V., W.C., Y.B., D.W., W.R.T., D.G.H.), Atlanta, Ga; Division of Rheumatology and Immunology (J.G., C.W.), Department of Medicine, Stanford University School of Medicine, Stanford, Calif; and Department of Medicine (T.J.G.), Jagiellonian University School of Medicine, Cracow, Poland.
Correspondence to David G. Harrison, Cardiology Division, Emory University School of Medicine, 1639 Pierce Dr, Atlanta, GA 30322. E-mail dharr02@emory.edu
Background— The pathogenesis of hypertension remains poorly understood, and treatment is often unsuccessful. Recent evidence suggests that the adaptive immune response plays an important role in this disease. Various hypertensive stimuli cause T-cell activation and infiltration into target organs such as the vessel and the kidney, which promotes vascular dysfunction and blood pressure elevation. Classically, T-cell activation requires T-cell receptor ligation and costimulation. The latter often involves interaction between B7 ligands (CD80 and CD86) on antigen-presenting cells with the T-cell coreceptor CD28. This study was therefore performed to examine the role of this pathway in hypertension.
Methods and Results— Angiotensin II–induced hypertension increased the presence of activated (CD86+) dendritic cells in secondary lymphatic tissues. Blockade of B7-dependent costimulation with CTLA4-Ig reduced both angiotensin II– and deoxycorticosterone acetate (DOCA)–salt–induced hypertension. Activation of circulating T cells, T-cell cytokine production, and vascular T-cell accumulation caused by these hypertensive stimuli were abrogated by CTLA4-Ig. Furthermore, in mice lacking B7 ligands, angiotensin II caused minimal blood pressure elevation and vascular inflammation, and these effects were restored by transplantation with wild-type bone marrow.
Conclusions— T-cell costimulation via B7 ligands is essential for development of experimental hypertension, and inhibition of this process could have therapeutic benefit in the treatment of this disease.
Abstract 6 of 8
Imaging
Myocardial Steatosis and Biventricular Strain and Strain Rate Imaging in Patients With Type 2 Diabetes Mellitus
Arnold C.T. Ng, MBBS; Victoria Delgado, MD, PhD; Matteo Bertini, MD, PhD; Rutger W. van der Meer, MD, PhD; Luuk J. Rijzewijk, MD; See Hooi Ewe, MBBS; Hans-Marc Siebelink, MD, PhD; Johannes W.A. Smit, MD, PhD; Michaela Diamant, MD, PhD; Johannes A. Romijn, MD, PhD; Albert de Roos, MD, PhD; Dominic Y. Leung, MBBS, PhD; Hildo J. Lamb, MD, PhD; Jeroen J. Bax, MD, PhD
From the Departments of Cardiology (A.C.T.N., V.D., MB., S.H.E., H.-M.S., J.J.B.), Radiology (R.W.v.d.M., A.d.R., H.J.L.), and Endocrinology (J.W.A.S., J.A.R.) Leiden University Medical Center, Leiden, the Netherlands; Department of Endocrinology, VU University Medical Center, Amsterdam, the Netherlands (L.J.R., M.D.); and Department of Cardiology, Liverpool Hospital, Sydney, New South Wales, Australia (D.Y.L.).
Correspondence to Jeroen J. Bax, MD, PhD, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. E-mail j.j.bax@lumc.nl
Background— Magnetic resonance spectroscopy can quantify myocardial triglyceride content in type 2 diabetic patients. Its relation to alterations in left (LV) and right (RV) ventricular myocardial functions is unknown.
Methods and Results— A total of 42 men with type 2 diabetes mellitus were recruited. Exclusion criteria included hemoglobin A1c >8.5, known cardiovascular disease, diabetes-related complications, or blood pressure >150/85 mm Hg. Myocardial ischemia was excluded by a negative dobutamine stress test. LV and RV volumes and ejection fraction were quantified by magnetic resonance imaging. LV global longitudinal and RV free wall longitudinal strain, systolic strain rate, and diastolic strain rate were quantified by echocardiographic speckle tracking analyses. Myocardial triglyceride content was quantified by magnetic resonance spectroscopy and dichotomized on the basis of the median value of 0.76. The median age was 59 years (25th and 75th percentiles, 54 and 62 years). Median diabetes diagnosis duration was 4 years, and median glycohemoglobin level was 6.2 (25th and 75th percentiles, 5.9 and 6.8). There were no differences in LV and RV end-diastolic and end-systolic volume indexes and ejection fraction between patients with high ( 0.76) and those with low (<0.76) myocardial triglyceride content. However, patients with high myocardial triglyceride content had greater impairment of LV and RV myocardial strain and strain rate. The myocardial triglyceride content was an independent correlate of LV and RV longitudinal strain, systolic strain rate, and diastolic strain rate.
Conclusions— High myocardial triglyceride content is associated with more pronounced impairment of LV and RV functions in men with uncomplicated type 2 diabetes mellitus.
Abstract 7 of 8
Interventional Cardiology
Economic Evaluation of Fractional Flow Reserve–Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease
William F. Fearon, MD; Bernhard Bornschein, MD, MPH; Pim A.L. Tonino, MD, PhD; Raffaella M. Gothe, BS; Bernard De Bruyne, MD, PhD; Nico H.J. Pijls, MD, PhD; Uwe Siebert, MD, MPH, MSc, ScD, for the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) Study Investigators
From the Stanford University Medical Center, Stanford, Calif (W.F.F.); University of Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria (B.B., R.M.G., U.S.); Catharina Hospital, Eindhoven, the Netherlands (P.A.L.T., N.H.J.P.); Cardiovascular Center Aalst, Aalst, Belgium (B.D.B.); and Massachusetts General Hospital, Harvard Medical School, Boston (U.S.).
Correspondence to William F. Fearon, MD, Division of Cardiovascular Medicine, Stanford University Medical Center, 300 Pasteur Dr, H2103, Stanford, CA 94305. E-mail wfearon@stanford.edu
Background— The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study demonstrated significantly improved health outcomes at 1 year in patients randomized to multivessel percutaneous coronary intervention guided by fractional flow reserve (FFR) compared with percutaneous coronary intervention guided by angiography alone. The economic impact of routine measurement of FFR in this setting is not known.
Methods and Results— In this study, 1005 patients were randomly assigned to FFR-guided or angiography-guided percutaneous coronary intervention and followed up for 1 year. A prospective cost-utility analysis comparing costs and quality-adjusted life-years was performed with a time horizon of 1 year. Quality-adjusted life-years were calculated with the use of utilities determined by the EuroQuol 5 dimension health survey with US weights. Direct medical costs included those of the index procedure and hospitalization and costs for major adverse cardiac events during follow-up. Confidence intervals for both quality-adjusted life-years and costs were estimated by the bootstrap percentile method. Major adverse cardiac events at 1 year occurred in 13.2% of those in the FFR-guided arm and 18.3% of those in the angiography-guided arm (P=0.02). Quality-adjusted life-years were slightly greater in the FFR-guided arm (0.853 versus 0.838; P=0.2). Mean overall costs at 1 year were significantly less in the FFR-guided arm ($14 315 versus $16 700; P<0.001). Bootstrap simulation indicated that the FFR-guided strategy was cost-saving in 90.74% and cost-effective at a threshold of US $50 000 per quality-adjusted life-years in 99.96%. Sensitivity analyses demonstrated robust results.
Conclusion— Economic evaluation of the FAME study reveals that FFR-guided percutaneous coronary intervention in patients with multivessel coronary disease is one of those rare situations in which a new technology not only improves outcomes but also saves resources.
Abstract 8 of 8
Stroke
Migraine and Functional Outcome From Ischemic Cerebral Events in Women
Pamela M. Rist, MSc; Julie E. Buring, ScD; Carlos S. Kase, MD; Markus Schürks, MD, MSc; Tobias Kurth, MD, ScD
From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (P.M.R., J.E.B., M.S., T.K.); Department of Epidemiology, Harvard School of Public Health, Boston, Mass (P.M.R., J.E.B., T.K.); Department of Neurology, Boston University School of Medicine, Boston, Mass (C.S.K); and INSERM Unit 708–Neuroepidemiology and University Pierre et Marie Curie, Paris, France (T.K.).
Correspondence to Tobias Kurth, MD, ScD, INSERM Unit 708–Neuroepidemiology, H?pital de la Pitié-Salpêtrière, 47 boulevard de l'H?pital, 75651 Paris Cedex 13, France. E-mail tkurth@rics.bwh.harvard.edu
Background— Studies have linked migraine with aura to an increased risk of ischemic stroke, particularly among women. Data on the relationship of migraine and functional outcome from ischemic cerebral events are sparse.
Methods and Results— This was a prospective cohort study among 27 852 women enrolled in the Women's Health Study for whom we had information on migraine and measured cholesterol values and who had no prior stroke or transient ischemic attack (TIA) at baseline. Migraine was classified into no history of migraine, active migraine with aura, active migraine without aura, and past history of migraine. Possible functional outcomes were no stroke or TIA, TIA, and stroke with modified Rankin Scale (mRS) score 0 to 1, mRS 2 to 3, and mRS 4 to 6. We used multinomial logistic regression to evaluate the relationship of migraine with functional outcomes after ischemic stroke. During a mean of 13.5 years of follow-up, 398 TIAs and 345 ischemic strokes occurred. Compared with women without history of migraine and who did not experience a TIA or stroke, women who reported migraine with aura had adjusted relative risk (95% confidence interval) of 1.56 (1.03 to 2.36) for TIA, 2.33 (1.37 to 3.97) for stroke with mRS 0 to 1, 0.82 (0.30 to 2.24) for mRS 2 to 3, and 1.18 (0.28 to 4.97) for mRS 4 to 6. The risk of any outcome was not significantly elevated for women who experienced migraine without aura or who had a past history of migraine.
Conclusions— Results of this large prospective cohort suggest that women with migraine with aura are at increased risk of experiencing TIA or ischemic stroke with good functional outcome.
Arrhythmia/Electrophysiology
Marked Variability in Susceptibility to Ventricular Fibrillation in an Experimental Commotio Cordis Model
Alawi A. Alsheikh-Ali, MD, MS; Christopher Madias, MD; Stacey Supran, MA; Mark S. Link, MD
From the Cardiac Arrhythmia Center, Division of Cardiology (C.M., M.S.L.), and Clinical Care Research Division (S.S.), Tufts Medical Center, Boston, Mass; and Institute of Cardiac Sciences, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates (A.A.A.-A.).
Correspondence to Mark S. Link, MD, Cardiac Arrhythmia Center, Division of Cardiology, Tufts Medical Center, 800 Washington St, Box 197, Boston, MA 02111. E-mail mlink@tuftsmedicalcenter.org
Background— Precordial blows in sports and daily activities can trigger ventricular fibrillation (VF) (commotio cordis). Whereas chest wall blows are common, commotio cordis is rare. Although factors such as timing, location, orientation, and energy of impact are critically important, we also hypothesize that there is individual susceptibility to commotio cordis. Using our model of commotio cordis, we evaluated individual animal susceptibility to VF induction and assessed animal characteristics that might be involved.
Methods and Results— This retrospective analysis included 139 juvenile swine (weight, 8 to 54 kg) that were anesthetized and placed prone in a sling to receive chest wall strikes with a ball propelled at 30 to 40 mph. Each animal received a minimum of 4 impacts directly over the cardiac silhouette, all timed to a narrow vulnerable window during cardiac repolarization. Of 1274 total impacts, 360 impacts (28%) resulted in VF. There was wide variability in individual animal susceptibility to VF. In 38 animals, none of the impacts resulted in VF (range, 4 to 18 impacts per animal). The majority of animals (91; 65%) were induced into VF with <30% of the strikes. In fact, only 19 animals (14%) had >50% occurrence of VF with chest wall impacts, and only 7 (5%) had >80% occurrence of chest impacts that induced VF. In the animal-based analysis, individual correlates of VF included animal weight, mean impact velocity, mean left ventricular pressure generated by the blow, mean QRS duration, mean QTc, and QTc variability. In multivariable analysis, mean left ventricular pressure generated by the blow, mean QRS duration, and QTc variability remained significant correlates of risk, and number of impacts gained statistical significance such that animals with more impacts were less susceptible to VF.
Conclusions— Swine display a wide range of individual vulnerability to VF triggered by chest wall impact, with a distinct minority being uniquely susceptible. Mild abnormalities in cardiac depolarization and repolarization might underlie this susceptibility. Such individual susceptibility may also be present in humans and contribute to the rarity of commotio cordis.
Abstract 2 of 8
Coronary Heart Disease
High Levels of Systemic Myeloperoxidase Are Associated With Coronary Plaque Erosion in Patients With Acute Coronary Syndromes
A Clinicopathological Study
Giuseppe Ferrante, MD, PhD; Masataka Nakano, MD; Francesco Prati, MD; Giampaolo Niccoli, MD, PhD; Maria T. Mallus, MD, PhD; Vito Ramazzotti, MD; Rocco A. Montone, MD; Frank D. Kolodgie, PhD; Renu Virmani, MD; Filippo Crea, MD, PhD
From the Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (G.F., G.N., R.A.M., F.C.); Cardiovascular Pathology Institute, Gaithersburg, Md (M.N., F.D.K., R.V.); Interventional Cardiology, San Giovanni Hospital, Rome, Italy (F.P., M.T.M., V.R.); and CLI Foundation, Rome, Italy (F.P.).
Correspondence to Filippo Crea, MD, PhD, Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy. E-mail filippo.crea@rm.unicatt.it
Background— Systemic levels of myeloperoxidase predict prognosis in patients with acute coronary syndromes and are considered a marker of plaque vulnerability. It is not known whether myeloperoxidase is associated with different coronary morphologies (ie, rupture or erosion of the culprit lesion) in patients with acute coronary syndrome.
Methods and Results— Twenty-five consecutive patients (aged 67±11 years; 15 men [60%]; 13 [52%] with non–ST-segment elevation acute coronary syndrome and 12 [48%] with acute ST-segment elevation myocardial infarction) were enrolled. Optical coherence tomography classified the culprit lesion as ruptured in 18 (72%) or eroded in 7 patients (28%) and detected intraluminal thrombus in 89% of ruptured plaques and 100% of eroded plaques. Baseline systemic levels of serum myeloperoxidase were significantly higher in patients with an eroded plaque than in those with a ruptured plaque (median, 2500 ng/mL; 25th to 75th percentile, 1415 to 2920 versus median, 707 ng/mL; 25th to 75th percentile, 312 to 943; P=0.001), whereas C-reactive protein levels did not differ significantly (median, 11.3 mg/L; 25th to 75th percentile, 1.3 to 28.5 versus median, 3.9 mg/L; 25th to 75th percentile, 1.3 to 17.8; P=0.76, respectively). In addition, the density of myeloperoxidase-positive cells within thrombi overlying plaques in postmortem coronary specimens retrieved from sudden coronary death victims was significantly higher in lesions with erosion (n=11) than ruptures (n=11) (median, 1584; 25th to 75th percentile, 1088 to 2135 cells/mm2 versus median, 579; 25th to 75th percentile, 442 to 760 cells/mm2; P=0.0012).
Conclusions— Systemic myeloperoxidase levels are significantly elevated in patients with acute coronary syndrome presenting with eroded culprit plaque compared with patients presenting with ruptured culprit plaque. Consistently, in postmortem coronary specimens, luminal thrombi superimposed on eroded plaques contain a higher density of myeloperoxidase-positive cells than thrombi superimposed on ruptured plaques. This study supports the concept that elevations in selective inflammatory biomarkers reflect specific acute complications of coronary atherosclerosis.
Abstract 3 of 8
Epidemiology and Prevention
Influence of Age on Associations Between Childhood Risk Factors and Carotid Intima-Media Thickness in Adulthood
The Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium
Markus Juonala, MD,, PhD*; Costan G. Magnussen, PhD*; Alison Venn, PhD; Terence Dwyer, MD,, MPH; Trudy L. Burns, MPH,, PhD; Patricia H. Davis, MD; Wei Chen, MD,, PhD; Sathanur R. Srinivasan, PhD; Stephen R. Daniels, MD,, PhD; Mika Khnen, MD,, PhD; Tomi Laitinen, MD,, PhD; Leena Taittonen, MD,, PhD; Gerald S. Berenson, MD; Jorma S.A. Viikari, MD,, PhD; Olli T. Raitakari, MD,, PhD
From the Research Centre of Applied and Preventive Cardiovascular Medicine (M.J., C.G.M., O.T.R.) and the Departments of Clinical Physiology (O.T.R.) and Medicine (M.J., J.S.A.V.), University of Turku and Turku University Hospital, Turku, Finland; Menzies Research Institute (C.G.M., A.V.), University of Tasmania, Hobart, Australia; Murdoch Children's Research Institute (C.G.M., T.D.), Melbourne, Australia; Department of Epidemiology, College of Public Health, and Department of Neurology, Carver College of Medicine, University of Iowa (T.L.B., P.H.D.), Iowa City, Iowa; Department of Epidemiology, Tulane Center for Cardiovascular Health (W.C., S.R.S., G.S.B.), Tulane University School of Public Health and Tropical Medicine, New Orleans, La; Department of Pediatrics, University of Colorado Denver and Health Science Center (S.R.D.), Aurora, Colo; Department of Clinical Physiology, Tampere University Hospital and University of Tampere (M.K.), Tampere, Finland; Department of Clinical Physiology, Kuopio University Hospital (T.L.), Kuopio, Finland; and Department of Pediatrics, Vaasa Central Hospital, Vaasa, Finland and Department of Pediatrics, University of Oulu (L.T.), Oulu, Finland.
Correspondence to Markus Juonala, Department of Medicine, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland. E-mail mataju@utu.fi
Background— Atherosclerosis has its roots in childhood. Therefore, defining the age when childhood risk exposure begins to relate to adult atherosclerosis may have implications for pediatric cardiovascular disease prevention and provide insights about the early determinants of atherosclerosis development. The aim of this study was to investigate the influence of age on the associations between childhood risk factors and carotid artery intima-media thickness, a marker of subclinical atherosclerosis.
Methods and Results— We used data for 4380 members of 4 prospective cohorts—Cardiovascular Risk in Young Finns Study (Finland), Childhood Determinants of Adult Health study (Australia), Bogalusa Heart Study (United States), and Muscatine Study (United States)—that have collected cardiovascular risk factor data from childhood (age 3 to 18 years) and performed intima-media thickness measurements in adulthood (age 20 to 45 years). The number of childhood risk factors (high [highest quintile] total cholesterol, triglycerides, blood pressure, and body mass index) was predictive of elevated intima-media thickness (highest decile) on the basis of risk factors measured at age 9 years (odds ratio [95% confidence interval] 1.37 [1.16 to 1.61], P=0.0003), 12 years (1.48 [1.28 to 1.72], P<0.0001), 15 years (1.56 [1.36 to 1.78], P<0.0001), and 18 years (1.57 [1.31 to 1.87], P<0.0001). The associations with risk factors measured at age 3 years (1.17 [0.80 to 1.71], P=0.42) and 6 years (1.20 [0.96 to 1.51], P=0.13) were weaker and nonsignificant.
Conclusions— Our analyses from 4 longitudinal cohorts showed that the strength of the associations between childhood risk factors and carotid intima-media thickness is dependent on childhood age. On the basis of these data, risk factor measurements obtained at or after 9 years of age are predictive of subclinical atherosclerosis in adulthood.
Abstract 4 of 8
Epidemiology and Prevention
Lifetime Fruit and Vegetable Consumption and Arterial Pulse Wave Velocity in Adulthood
The Cardiovascular Risk in Young Finns Study
Heikki Aatola, MD; Teemu Koivistoinen, MD, MSc; Nina Hutri-K?h?nen, MD, PhD; Markus Juonala, MD, PhD; Vera Mikkil?, PhD; Terho Lehtim?ki, MD, PhD; Jorma S.A. Viikari, MD, PhD; Olli T. Raitakari, MD, PhD; Mika K?h?nen, MD, PhD
From the Departments of Clinical Physiology (H.A., T.K., M.K.), Pediatrics (N.H.-K.), and Clinical Chemistry (T.L.), University of Tampere and Tampere University Hospital, Tampere, Finland; Departments of Medicine (M.J., J.S.A.V.) and Clinical Physiology (O.T.R.) and Research Centre of Applied and Preventive Cardiovascular Medicine (M.J., O.T.R.), University of Turku and Turku University Hospital, Turku, Finland; and Division of Nutrition, University of Helsinki, Helsinki, Finland (V.M.).
Correspondence to Mika K?h?nen, MD, PhD, Department of Clinical Physiology, Tampere University Hospital, PO Box 2000, FI-33521 Tampere, Finland. E-mail mika.kahonen@uta.fi
Background— The relationships between childhood lifestyle risk factors and adulthood pulse wave velocity (PWV) have not been reported. We studied whether childhood and adulthood lifestyle risk factors are associated with PWV assessed in adulthood.
Methods and Results— The study cohort comprised 1622 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (1980; aged 3 to 18 years) with lifestyle risk factor data available since childhood. Arterial PWV was measured in 2007 by whole-body impedance cardiography device. Vegetable consumption in childhood was inversely associated with adulthood PWV (β=–0.06, P=0.02), and this association remained significant (β=–0.07, P=0.004) when adjusted for traditional risk factors (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, body mass index, and smoking). Vegetable consumption was also an independent predictor of PWV in adulthood when adjusted for lifestyle or traditional risk factors (β=–0.08, P=0.002 and β=–0.07, P=0.0007, respectively). Persistently high consumption of both fruits and vegetables from childhood to adulthood was associated with lower PWV compared with persistently low consumption (P=0.03 for both). The number of lifestyle risk factors (the lowest quintile for vegetable consumption, fruit consumption, physical activity, and smoking) in childhood was directly associated with PWV in adulthood (P=0.001). This association remained significant when adjusted for the number of lifestyle risk factors in adulthood (P=0.003).
Conclusions— These findings suggest that lifetime lifestyle risk factors, with low consumption of fruits and vegetables in particular, are related to arterial stiffness in young adulthood.
Abstract 5 of 8
Hypertension
Inhibition and Genetic Ablation of the B7/CD28 T-Cell Costimulation Axis Prevents Experimental Hypertension
Antony Vinh, PhD; Wei Chen, PhD; Yelena Blinder, MD; Daiana Weiss, PhD; W. Robert Taylor, MD, PhD; J?rg J. Goronzy, MD, PhD; Cornelia M. Weyand, MD, PhD; David G. Harrison, MD, PhD; Tomasz J. Guzik, MD, PhD
From the Division of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta Veteran Administration Hospital (A.V., W.C., Y.B., D.W., W.R.T., D.G.H.), Atlanta, Ga; Division of Rheumatology and Immunology (J.G., C.W.), Department of Medicine, Stanford University School of Medicine, Stanford, Calif; and Department of Medicine (T.J.G.), Jagiellonian University School of Medicine, Cracow, Poland.
Correspondence to David G. Harrison, Cardiology Division, Emory University School of Medicine, 1639 Pierce Dr, Atlanta, GA 30322. E-mail dharr02@emory.edu
Background— The pathogenesis of hypertension remains poorly understood, and treatment is often unsuccessful. Recent evidence suggests that the adaptive immune response plays an important role in this disease. Various hypertensive stimuli cause T-cell activation and infiltration into target organs such as the vessel and the kidney, which promotes vascular dysfunction and blood pressure elevation. Classically, T-cell activation requires T-cell receptor ligation and costimulation. The latter often involves interaction between B7 ligands (CD80 and CD86) on antigen-presenting cells with the T-cell coreceptor CD28. This study was therefore performed to examine the role of this pathway in hypertension.
Methods and Results— Angiotensin II–induced hypertension increased the presence of activated (CD86+) dendritic cells in secondary lymphatic tissues. Blockade of B7-dependent costimulation with CTLA4-Ig reduced both angiotensin II– and deoxycorticosterone acetate (DOCA)–salt–induced hypertension. Activation of circulating T cells, T-cell cytokine production, and vascular T-cell accumulation caused by these hypertensive stimuli were abrogated by CTLA4-Ig. Furthermore, in mice lacking B7 ligands, angiotensin II caused minimal blood pressure elevation and vascular inflammation, and these effects were restored by transplantation with wild-type bone marrow.
Conclusions— T-cell costimulation via B7 ligands is essential for development of experimental hypertension, and inhibition of this process could have therapeutic benefit in the treatment of this disease.
Abstract 6 of 8
Imaging
Myocardial Steatosis and Biventricular Strain and Strain Rate Imaging in Patients With Type 2 Diabetes Mellitus
Arnold C.T. Ng, MBBS; Victoria Delgado, MD, PhD; Matteo Bertini, MD, PhD; Rutger W. van der Meer, MD, PhD; Luuk J. Rijzewijk, MD; See Hooi Ewe, MBBS; Hans-Marc Siebelink, MD, PhD; Johannes W.A. Smit, MD, PhD; Michaela Diamant, MD, PhD; Johannes A. Romijn, MD, PhD; Albert de Roos, MD, PhD; Dominic Y. Leung, MBBS, PhD; Hildo J. Lamb, MD, PhD; Jeroen J. Bax, MD, PhD
From the Departments of Cardiology (A.C.T.N., V.D., MB., S.H.E., H.-M.S., J.J.B.), Radiology (R.W.v.d.M., A.d.R., H.J.L.), and Endocrinology (J.W.A.S., J.A.R.) Leiden University Medical Center, Leiden, the Netherlands; Department of Endocrinology, VU University Medical Center, Amsterdam, the Netherlands (L.J.R., M.D.); and Department of Cardiology, Liverpool Hospital, Sydney, New South Wales, Australia (D.Y.L.).
Correspondence to Jeroen J. Bax, MD, PhD, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. E-mail j.j.bax@lumc.nl
Background— Magnetic resonance spectroscopy can quantify myocardial triglyceride content in type 2 diabetic patients. Its relation to alterations in left (LV) and right (RV) ventricular myocardial functions is unknown.
Methods and Results— A total of 42 men with type 2 diabetes mellitus were recruited. Exclusion criteria included hemoglobin A1c >8.5, known cardiovascular disease, diabetes-related complications, or blood pressure >150/85 mm Hg. Myocardial ischemia was excluded by a negative dobutamine stress test. LV and RV volumes and ejection fraction were quantified by magnetic resonance imaging. LV global longitudinal and RV free wall longitudinal strain, systolic strain rate, and diastolic strain rate were quantified by echocardiographic speckle tracking analyses. Myocardial triglyceride content was quantified by magnetic resonance spectroscopy and dichotomized on the basis of the median value of 0.76. The median age was 59 years (25th and 75th percentiles, 54 and 62 years). Median diabetes diagnosis duration was 4 years, and median glycohemoglobin level was 6.2 (25th and 75th percentiles, 5.9 and 6.8). There were no differences in LV and RV end-diastolic and end-systolic volume indexes and ejection fraction between patients with high ( 0.76) and those with low (<0.76) myocardial triglyceride content. However, patients with high myocardial triglyceride content had greater impairment of LV and RV myocardial strain and strain rate. The myocardial triglyceride content was an independent correlate of LV and RV longitudinal strain, systolic strain rate, and diastolic strain rate.
Conclusions— High myocardial triglyceride content is associated with more pronounced impairment of LV and RV functions in men with uncomplicated type 2 diabetes mellitus.
Abstract 7 of 8
Interventional Cardiology
Economic Evaluation of Fractional Flow Reserve–Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease
William F. Fearon, MD; Bernhard Bornschein, MD, MPH; Pim A.L. Tonino, MD, PhD; Raffaella M. Gothe, BS; Bernard De Bruyne, MD, PhD; Nico H.J. Pijls, MD, PhD; Uwe Siebert, MD, MPH, MSc, ScD, for the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) Study Investigators
From the Stanford University Medical Center, Stanford, Calif (W.F.F.); University of Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria (B.B., R.M.G., U.S.); Catharina Hospital, Eindhoven, the Netherlands (P.A.L.T., N.H.J.P.); Cardiovascular Center Aalst, Aalst, Belgium (B.D.B.); and Massachusetts General Hospital, Harvard Medical School, Boston (U.S.).
Correspondence to William F. Fearon, MD, Division of Cardiovascular Medicine, Stanford University Medical Center, 300 Pasteur Dr, H2103, Stanford, CA 94305. E-mail wfearon@stanford.edu
Background— The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study demonstrated significantly improved health outcomes at 1 year in patients randomized to multivessel percutaneous coronary intervention guided by fractional flow reserve (FFR) compared with percutaneous coronary intervention guided by angiography alone. The economic impact of routine measurement of FFR in this setting is not known.
Methods and Results— In this study, 1005 patients were randomly assigned to FFR-guided or angiography-guided percutaneous coronary intervention and followed up for 1 year. A prospective cost-utility analysis comparing costs and quality-adjusted life-years was performed with a time horizon of 1 year. Quality-adjusted life-years were calculated with the use of utilities determined by the EuroQuol 5 dimension health survey with US weights. Direct medical costs included those of the index procedure and hospitalization and costs for major adverse cardiac events during follow-up. Confidence intervals for both quality-adjusted life-years and costs were estimated by the bootstrap percentile method. Major adverse cardiac events at 1 year occurred in 13.2% of those in the FFR-guided arm and 18.3% of those in the angiography-guided arm (P=0.02). Quality-adjusted life-years were slightly greater in the FFR-guided arm (0.853 versus 0.838; P=0.2). Mean overall costs at 1 year were significantly less in the FFR-guided arm ($14 315 versus $16 700; P<0.001). Bootstrap simulation indicated that the FFR-guided strategy was cost-saving in 90.74% and cost-effective at a threshold of US $50 000 per quality-adjusted life-years in 99.96%. Sensitivity analyses demonstrated robust results.
Conclusion— Economic evaluation of the FAME study reveals that FFR-guided percutaneous coronary intervention in patients with multivessel coronary disease is one of those rare situations in which a new technology not only improves outcomes but also saves resources.
Abstract 8 of 8
Stroke
Migraine and Functional Outcome From Ischemic Cerebral Events in Women
Pamela M. Rist, MSc; Julie E. Buring, ScD; Carlos S. Kase, MD; Markus Schürks, MD, MSc; Tobias Kurth, MD, ScD
From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (P.M.R., J.E.B., M.S., T.K.); Department of Epidemiology, Harvard School of Public Health, Boston, Mass (P.M.R., J.E.B., T.K.); Department of Neurology, Boston University School of Medicine, Boston, Mass (C.S.K); and INSERM Unit 708–Neuroepidemiology and University Pierre et Marie Curie, Paris, France (T.K.).
Correspondence to Tobias Kurth, MD, ScD, INSERM Unit 708–Neuroepidemiology, H?pital de la Pitié-Salpêtrière, 47 boulevard de l'H?pital, 75651 Paris Cedex 13, France. E-mail tkurth@rics.bwh.harvard.edu
Background— Studies have linked migraine with aura to an increased risk of ischemic stroke, particularly among women. Data on the relationship of migraine and functional outcome from ischemic cerebral events are sparse.
Methods and Results— This was a prospective cohort study among 27 852 women enrolled in the Women's Health Study for whom we had information on migraine and measured cholesterol values and who had no prior stroke or transient ischemic attack (TIA) at baseline. Migraine was classified into no history of migraine, active migraine with aura, active migraine without aura, and past history of migraine. Possible functional outcomes were no stroke or TIA, TIA, and stroke with modified Rankin Scale (mRS) score 0 to 1, mRS 2 to 3, and mRS 4 to 6. We used multinomial logistic regression to evaluate the relationship of migraine with functional outcomes after ischemic stroke. During a mean of 13.5 years of follow-up, 398 TIAs and 345 ischemic strokes occurred. Compared with women without history of migraine and who did not experience a TIA or stroke, women who reported migraine with aura had adjusted relative risk (95% confidence interval) of 1.56 (1.03 to 2.36) for TIA, 2.33 (1.37 to 3.97) for stroke with mRS 0 to 1, 0.82 (0.30 to 2.24) for mRS 2 to 3, and 1.18 (0.28 to 4.97) for mRS 4 to 6. The risk of any outcome was not significantly elevated for women who experienced migraine without aura or who had a past history of migraine.
Conclusions— Results of this large prospective cohort suggest that women with migraine with aura are at increased risk of experiencing TIA or ischemic stroke with good functional outcome.
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