Publications by authors named "Philip Aagaard"

26 Publications

  • Page 1 of 1

Early repolarization pattern in an ethnically diverse population: Increased risk in Hispanics.

Pacing Clin Electrophysiol 2020 01 22;43(1):30-36. Epub 2019 Dec 22.

Division of Cardiology, Department of Medicine, Montefiore Medical Center, Bronx, New York.

Background: Early repolarization (ER) pattern on ECG is associated with an increased mortality in Caucasians. This study analyzed the association between ER pattern and all-cause mortality in a population of multiple ethnicities.

Methods: A total of 20 000 individuals were randomly selected and their ECGs were analyzed for ER pattern using the 2015 consensus: end-QRS notching or slurring with a J-point (Jp) ≥0.1 mV in contiguous inferior or lateral leads. Exclusion criteria were age <18, QRS duration of ≥120 ms, and acute myocardial infarction. Kaplan-Meier survival curves were used to assess crude survival, and multivariable logistic regression models were used to determine predictors of all-cause mortality.

Results: A total of 17 901 patients with a mean age of 53 met inclusion criteria. Individuals were 62% female, 14% White, 37% Black, 40% Hispanic, and 9% other. Median follow-up time was 6.4 years. ER pattern was noted in 995 (5.6%) patients. Jp ≥2 mm was noted in 282 (1.6%) patients. In those with ER pattern and Jp ≥1 mm, there was no difference in mortality when compared to individuals without Jp elevation (odds ratio [OR]: 0.962, 95% confidence of interval [CI]: 0.819-1.131). Patients with Jp ≥2 mm had a significantly increased all-cause mortality (OR: 1.333, 95% CI: 1.009-1.742). This increased mortality was also significant in Hispanic patients with Jp ≥2 mm (OR: 1.584, 95% CI: 1.003-2.502).

Conclusion: ER pattern with Jp ≥2 mm is associated with increased mortality in a multiethnic population, apparently driven by an increased risk in Hispanics.
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http://dx.doi.org/10.1111/pace.13827DOI Listing
January 2020

Cardiac devices in patients with transthyretin amyloidosis: Impact on functional class, left ventricular function, mitral regurgitation, and mortality.

J Cardiovasc Electrophysiol 2019 11 25;30(11):2427-2432. Epub 2019 Sep 25.

Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.

Background: The aim of our study was to investigate outcomes of patients with ATTR (amyloidosis and transthyretin) CA (cardiac amyloidosis) and implantable devices with respect to left ventricular ejection fraction (LVEF), mitral regurgitation (MR), New York Heart Association (NYHA) functional class, and mortality.

Methods: This was a retrospective observational cohort study of 78 patients with ATTR CA and implantable devices. During a mean follow-up of 42 months we investigated the impact of right ventricular (RV) pacing burden and biventricular (BiV) pacing on LVEF, MR severity, NYHA functional class, and mortality.

Results: Worsening MR occurred in 11% of patients with a RV pacing % <40% compared to 62% of those with a RV pacing burden >40% (P = .002). Similarly, worsening LVEF occurred in 26% of patients who were RV paced <40% and 89% of those who were RV paced >40% of the time (P < .0001) and worsening in NYHA functional class occurred in 22% and 89%, respectively (P < .0001). Improvement in LVEF, NYHA functional class, and MR severity occurred in 78%, 67%, and 67%, respectively, in those with BiV devices. Death occurred in 67% of patients in the cardiac resynchronization therapy group compared to 68% of those with a RV pacing burden <40% and 92% of those with a RV pacing burden >40%.

Conclusion: A higher RV pacing burden is associated with deleterious remodeling and congestive heart failure in patients with ATTR CA, whereas BiV pacing is associated with improvements in LVEF, NYHA class, and degree of MR. BiV pacing should be considered in patients with ATTR CA and an indication for pacing. However, further larger prospective studies will need to be performed.
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http://dx.doi.org/10.1111/jce.14180DOI Listing
November 2019

Association Between Pre-Ablation Glycemic Control and Outcomes Among Patients With Diabetes Undergoing Atrial Fibrillation Ablation.

JACC Clin Electrophysiol 2019 08 31;5(8):897-903. Epub 2019 Jul 31.

Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Objectives: The aim of this study was to investigate the impact of improved glycemic control on atrial fibrillation (AF) recurrence rates after ablation.

Background: Diabetes is associated with increased rates of AF. The impact of improved pre-ablation glycemic control remains unknown.

Methods: The 12-month pre-ablation trends in glycemic control were studied in 298 patients with diabetes undergoing AF ablation. Recurrence data were obtained during a mean follow-up period of 25.92 ± 20.26 months post-ablation.

Results: Higher glycated hemoglobin (HbA) at the time of ablation was associated with higher post-ablation recurrence rates. More than two-thirds (68.75%) of patients with HbA >9% at the time of ablation developed recurrent AF, compared with 32.4% of those with HbA <7% (p < 0.0001). On multivariate analysis, only the 12-month trend in HbA was significantly associated with AF recurrence. Although 91.1% of patients with a worsening trend in HbA during the 12 months prior to ablation developed recurrent AF, only 2% of patients with improvements in HbA of 10% or more experienced AF recurrence (p < 0.0001).

Conclusions: The trend in glycemic control prior to ablation predicts arrhythmia recurrence after ablation. A multidisciplinary approach to reduce HbA is imperative in patients with diabetes with AF to reduce recurrence rates after ablation.
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http://dx.doi.org/10.1016/j.jacep.2019.05.018DOI Listing
August 2019

Arrhythmias and Adaptations of the Cardiac Conduction System in Former National Football League Players.

J Am Heart Assoc 2019 08 24;8(15):e010401. Epub 2019 Jul 24.

Department of Cardiovascular Medicine, Heart and Vascular Institute Cleveland Clinic Foundation Cleveland OH.

Background Habitual high-intensity endurance exercise is associated with increased atrial fibrillation (AF) risk and impaired cardiac conduction. It is unknown whether these observations extend to prior strength-type sports exposure. The primary aim of this study was to compare AF prevalence in former National Football League (NFL) athletes to population-based controls. The secondary aim was to characterize other conduction system parameters. Methods and Results This cross-sectional study compared former NFL athletes (n=460, age 56±12 years, black 47%) with population-based controls of similar age and racial composition from the cardiovascular cohort Dallas Heart Study-2 (n=925, age 54±9 years, black 53%). AF was present in 28 individuals (n=23 [5%] in the NFL group; n=5 [0.5%] in the control group). After controlling for other cardiovascular risk factors in multivariable regression analysis, former NFL participation remained associated with a 5.7 (95% CI: 2.1-15.9, P<0.001) higher odds ratio of AF. Older age, higher body mass index, and nonblack race were also independently associated with higher odds ratio of AF, while hypertension and diabetes mellitus were not. AF was previously undiagnosed in 15/23 of the former NFL players. Previously undiagnosed NFL players were rate controlled and asymptomatic, but 80% had a CHADS-VASc score ≥1. Former NFL players also had an 8-fold higher prevalence of paced cardiac rhythms (2.0% versus 0.25%, P<0.01), compared with controls. Furthermore, former athletes had lower resting heart rates (62±11 versus 66±11 beats per minute, P<0.001), and a higher prevalence of first-degree atrioventricular block (18% versus 9%, P<0.001). Conclusions Former NFL participation was associated with an increased AF prevalence and slowed cardiac conduction when compared with a population-based control group. Former NFL athletes who screened positive for AF were generally rate controlled and asymptomatic, but 80% should have been considered for anticoagulation based on their stroke risk.
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http://dx.doi.org/10.1161/JAHA.118.010401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761649PMC
August 2019

Association between pre-ablation bariatric surgery and atrial fibrillation recurrence in morbidly obese patients undergoing atrial fibrillation ablation.

Europace 2019 Oct;21(10):1476-1483

Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave J2-2, Cleveland, OH, USA.

Aims: Obesity decreases arrhythmia-free survival after atrial fibrillation (AF) ablation by mechanisms that are not fully understood. We investigated the impact of pre-ablation bariatric surgery (BS) on AF recurrence after ablation.

Methods And Results: In this retrospective observational cohort study, 239 consecutive morbidly obese patients (body mass index ≥40 kg/m2 or ≥35 kg/m2 with obesity-related complications) were followed for a mean of 22 months prior to ablation. Of these patients, 51 had BS prior to ablation, and our primary outcome was whether BS was associated with a lower rate of AF recurrence during follow-up. Adjustment for confounding was performed with multivariable Cox proportional hazard models and propensity-score based analyses. During a mean follow-up of 36 months after ablation, 10/51 patients (20%) in the BS group had recurrent AF compared with 114/188 (61%) in the non-BS group (P < 0.0001). In the BS group, 6 patients (12%) underwent repeat ablation compared with 77 patients (41%) in the non-BS group, (P < 0.0001). On multivariable analysis, the association between BS and lower AF recurrence remained significant. Similarly, after weighting and adjusting for the inverse probability of the propensity score, BS was still associated with a lower hazard of AF recurrence (hazard ratio 0.14, 95% confidence interval 0.05-0.39; P = 0.002).

Conclusion: Bariatric surgery is associated with a lower AF recurrence after ablation. Morbidly obese patients should be considered for BS prior to AF ablation, though prospective multicentre studies should be performed to confirm our novel finding.
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http://dx.doi.org/10.1093/europace/euz183DOI Listing
October 2019

Ascending Aortic Dimensions in Former National Football League Athletes.

Circ Cardiovasc Imaging 2017 Nov;10(11)

From the Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic Foundation, OH (J.L.G., P.A., R.H., M.Y.D., E.E.R., D.M.P.); Division of Cardiology, UT Southwestern Medical Center, Dallas, TX (D.C., P.H.J., C.D.M., C.R.A., J.A.d.L.); Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD (P.H.J.); and MedStar Sports Medicine Research Center, Baltimore, MD (R.E.D., K.A., A.E.L., A.M.T.).

Background: Ascending aortic dimensions are slightly larger in young competitive athletes compared with sedentary controls, but rarely >40 mm. Whether this finding translates to aortic enlargement in older, former athletes is unknown.

Methods And Results: This cross-sectional study involved a sample of 206 former National Football League (NFL) athletes compared with 759 male subjects from the DHS-2 (Dallas Heart Study-2; mean age of 57.1 and 53.6 years, respectively, <0.0001; body surface area of 2.4 and 2.1 m, respectively, <0.0001). Midascending aortic dimensions were obtained from computed tomographic scans performed as part of a NFL screening protocol or as part of the DHS. Compared with a population-based control group, former NFL athletes had significantly larger ascending aortic diameters (38±5 versus 34±4 mm; <0.0001). A significantly higher proportion of former NFL athletes had an aorta of >40 mm (29.6% versus 8.6%; <0.0001). After adjusting for age, race, body surface area, systolic blood pressure, history of hypertension, current smoking, diabetes mellitus, and lipid profile, the former NFL athletes still had significantly larger ascending aortas (<0.0001). Former NFL athletes were twice as likely to have an aorta >40 mm after adjusting for the same parameters.

Conclusions: Ascending aortic dimensions were significantly larger in a sample of former NFL athletes after adjusting for their size, age, race, and cardiac risk factors. Whether this translates to an increased risk is unknown and requires further evaluation.
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http://dx.doi.org/10.1161/CIRCIMAGING.117.006852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728154PMC
November 2017

Socioeconomic status and the development of atrial fibrillation in Hispanics, African Americans and non-Hispanic whites.

Clin Cardiol 2017 Sep 9;40(9):770-776. Epub 2017 Jun 9.

Division of Cardiology, Department of Medicine, Montefiore Medical Center, New York.

Background: Atrial fibrillation (AF) is the most common arrhythmia and is associated with significant morbidity and mortality. Despite having a higher burden of traditional AF risk factors, African American and Hispanic minorities have a lower incidence of AF when compared to non-Hispanic whites, referred to as the "racial paradox."

Hypothesis: Lower SES among Hispanics and African Americans may help to explain the lower incidence rates of AF compared to non-Hispanic whites.

Methods: An electrocardiogram/electronic medical records database in New York State was interrogated for individuals free of AF for development of subsequent AF from 2000 to 2013. SES was assessed per zip code via a composite of 6 measures Z-scored to the New York State average. SES was reclassified into decile groups. Cox regression analysis controlling for all baseline differences was used to estimate the independent predictive ability of SES for AF.

Results: We identified 48 631 persons (43% Hispanic, 37% African Americans, and 20% non-Hispanic white; mean age 59 years; mean follow-up of 3.2 years) of which 4556 AF cases occurred. Hispanics and African Americans had lower AF risk than whites in all SES deciles (P < 0.001 by log-rank test). Higher SES was borderline associated with lower AF risk (hazard ratio: 0.990, 95% confidence interval: 0.980-1.001, P = 0.061). P trend analysis was not significant by any race/ethnic group by SES deciles for AF.

Conclusions: Our study suggests that non-Hispanic whites were at higher risk for AF compared to nonwhites, and this was independent of SES.
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http://dx.doi.org/10.1002/clc.22732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490556PMC
September 2017

Socioeconomic Status as a Predictor of Mortality in Patients Admitted With Atrial Fibrillation.

Am J Cardiol 2017 05 16;119(9):1378-1381. Epub 2017 Mar 16.

Division of Cardiology, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Electronic address:

Lower socioeconomic status (SES) is associated with a higher risk of cardiovascular disease. However, the association between SES and mortality in patients with atrial fibrillation (AF) is not clear. We examined whether SES predicts all-cause mortality in patients hospitalized with AF. This is a retrospective study of patients aged >18 years, admitted with a primary diagnosis of AF to Montefiore Medical Center between 2000 and 2010. Multivariable logistic regression models were used to determine predictors of survival adjusted for age, gender, heart failure, diabetes mellitus, chronic kidney disease, previous myocardial infraction, chronic obstructive pulmonary disease, hypertension, peripheral vascular disease, and SES. SES was determined using the New York City Department of Health Standardized Score (a log composite score of household income, value of housing units, net rental income, household occupations, and educational level). The cohort was divided into quartiles based on SES score, with Q4 the highest and Q1 the lowest SES score. There were 4,503 patients identified with a mean follow up of 4.5 years in the following SES quartiles: Q1 (n = 1,132), Q2 (n = 1,119), Q3 (n = 1,126), and Q4 (n = 1,126). The unadjusted mortality varied across quartiles (Q1 to Q4), 54%, 58%, 56%, and 59%, respectively (p = 0.004). After controlling for other variables in the multivariable analysis, patients with the lowest SES (Q1) had a significantly higher mortality than patients in the quartile with the highest (Q4) SES (odds ratio 1.3, CI 1.1 to 1.5). In conclusion, patients admitted to the hospital with AF have varying mortality based on their SES. After controlling for co-morbidities, patients with AF and lower SES scores had higher mortality. Further research studies are warranted to study this risk of increased mortality in AF population.
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http://dx.doi.org/10.1016/j.amjcard.2017.01.041DOI Listing
May 2017

State Requirements for Automated External Defibrillators in American Schools: Framing the Debate About Legislative Action.

J Am Coll Cardiol 2017 Apr;69(13):1735-1743

Mailman School of Public Health, Columbia University, New York, New York.

Installation of automated external defibrillators (AEDs) in schools has been associated with increased survival after sudden cardiac arrest. An authoritative academic research database was interrogated to identify all current state statutes pertaining to AEDs in schools. As of February 2016, 17 of 50 U.S. states (34%) require AED installation in at least some of their schools; the remaining states have no legislation. However, requirements are far from comprehensive in these 17 states. Only 5 states offer unequivocal funding to schools for purchasing AEDs. A minority of U.S. states have legislation requiring AED placement in schools, and even fewer provide funding. State legislatures that have not yet enacted legislation requiring AEDs in schools may look to neighboring states for examples of child and adult lifesaving law. Placement of an AED in schools should be implemented with an emergency response plan that trains staff in the recognition and response to cardiac arrest.
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http://dx.doi.org/10.1016/j.jacc.2017.01.033DOI Listing
April 2017

Atrial Fibrillation Ablation and Stroke.

Cardiol Clin 2016 May;34(2):307-16

Department of Cardiology, Texas Cardiac Arrhythmia Institute, St David's Medical Center, Austin, TX, USA; Department of Cardiology, University of Foggia, Foggia, Italy; Department of Biomedical Engineering, University of Texas, Austin, TX, USA. Electronic address:

Catheter ablation has become a widely available and accepted treatment to restore sinus rhythm in atrial fibrillation patients who fail antiarrhythmic drug therapy. Although generally safe, the procedure carries a non-negligible risk of complications, including periprocedural cerebral insults. Uninterrupted anticoagulation, maintenance of an adequate ACT during the procedure, and measures to avoid and detect thrombus build-up on sheaths and atheters during the procedure, appears useful to reduce the risk of embolic events. This is a review of the incidence, mechanisms, impact, and methods to reduce catheter ablation related cerebral insults.
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http://dx.doi.org/10.1016/j.ccl.2015.12.012DOI Listing
May 2016

Remote Magnetic Navigation: A Focus on Catheter Ablation of Ventricular Arrhythmias.

J Cardiovasc Electrophysiol 2016 Mar;27 Suppl 1:S38-44

Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.

VT ablation is based on percutaneous catheter insertion under fluoroscopic guidance to selectively destroy (i.e., ablate) myocardial tissue regions responsible for the initiation or propagation of ventricular arrhythmias. Although the last decade has witnessed a rapid evolution of ablation equipment and techniques, the control over catheter movement during manual ablation has remained largely unchanged. Moreover, the procedures are long, and require ergonomically unfavorable positions, which can lead to operator fatigue. In an attempt to overcome these constraints, several technical advancements, including remote magnetic navigation (RMN), have been developed. RMN utilizes a magnetic field to remotely manipulate specially designed soft-tip ablation catheters anywhere in the x, y, or z plane inside the patient's chest. RMN also facilitates titration of the contact force between the catheter and the myocardial tissue, which may reduce the risk of complications while ensuring adequate lesion formation. There are several non-randomized studies showing that RMN has similar efficacy to manual ablation, while complication rates and total radiation exposure appears to be lower. Although these data are promising, larger randomized studies are needed to prove that RMN is superior to manual ablation of VT.
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http://dx.doi.org/10.1111/jce.12938DOI Listing
March 2016

Early Repolarization in Athletes: A Review.

Circ Arrhythm Electrophysiol 2016 Mar;9(3):e003577

From the Department of Cardiovascular Medicine, Cleveland Clinic Foundation, OH.

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http://dx.doi.org/10.1161/CIRCEP.115.003577DOI Listing
March 2016

Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

Am J Cardiol 2016 Jan 19;117(1):76-83. Epub 2015 Oct 19.

Division of Cardiology, Department of Medicine, Montefiore Medical Center, Bronx, New York. Electronic address:

A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts.
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http://dx.doi.org/10.1016/j.amjcard.2015.10.009DOI Listing
January 2016

[Early repolarization in ECG. Definition, prevalence and prognostic significance].

Lakartidningen 2015 Oct 20;112. Epub 2015 Oct 20.

Hjärtkliniken, Karolinska Universitetssjukhuset - Stockholm, Sweden - .

Early repolarization defined as antero-lateral ST-segment elevation exists in 1-2 % of the general population and has been considered a benign ECG finding for decades. However, early repolarization, defined as infero-lateral J-waves, has in recent studies been associated with an increased - albeit low - risk of sudden and cardiovascular death. This ECG pattern is present in 3-13% of the general population. However, exercise training can induce all types of early repolarization, and the prevalence in the athletic population rises to 20-90%. There is large variability between sports (higher in endurance athletes) and also throughout the season (higher during times of peak fitness). In athletes, early repolarization, regardless of type, is considered benign. In asymptomatic non-athletes, the absolute risk is too low to use this ECG finding in clinical practice. In individuals with J-wave syndrome, on the other hand, ICD implantation should be strongly considered to prevent sudden cardiac death.
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October 2015

The Prognostic Value of Early Repolarization with ST-Segment Elevation by Age and Gender in the Hispanic Population.

Pacing Clin Electrophysiol 2015 Dec 6;38(12):1396-404. Epub 2015 Sep 6.

 Division of Cardiology, Department of Medicine, Montefiore Medical Center, Bronx, New York.

Background: Early repolarization (ER), once thought to be a benign finding on electrocardiograph (ECG), has recently been associated with an increased risk of sudden cardiac death. As there are limited data in the Hispanic population, we investigated possible associations between automated ECG ER readings and overall mortality, using the classic definition involving J-point elevation with ST segment elevation.

Methods: An ECG and electronic medical record (EMR) database from a regional medical center was interrogated. Inclusion criteria included Hispanic ethnicity and age over 18 from 2000 to 2011. A Cox model assessed the outcome of death. Varying morphological characteristics of ER were analyzed for high-risk features.

Results: There were n = 33,944 Hispanics of who n = 532 (1.6%) had ER with a mean follow-up period of 5.29 years. After adjustment for demographic, clinical, lifestyle, and laboratory variables, ER was not significantly related to all-cause mortality (hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 0.90-1.54, P = 0.23). However, mortality risk of ER varied by gender and age (P interaction = 0.007). The risk of ER for mortality was highest for females (HR: 2.01, CI: 1.39-3.10, P = 0.001), with the highest overall risk for women over the age of 75 (HR: 2.09, CI: 1.12-3.92, P = 0.021) compared to women under age 75 (HR: 1.72, CI: 0.95-3.11, P = 0.075).

Conclusions: ER is not associated with an increased risk of death in the overall Hispanic population. However, our analysis suggests a higher risk of overall mortality in the elderly Hispanic female population with ER.
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http://dx.doi.org/10.1111/pace.12730DOI Listing
December 2015

Left Atrial Appendage Occlusion Device and Novel Oral Anticoagulants Versus Warfarin for Stroke Prevention in Nonvalvular Atrial Fibrillation: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Circ Arrhythm Electrophysiol 2015 Oct 30;8(5):1057-64. Epub 2015 Jul 30.

From the Department of Medicine, Division of Cardiology, Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY (D.F.B., P.V., N.C., D.M., E.B., E.M., P.A., K.F., J.G., S.G.K., A.K., E.P., N.G., J.R., J.F., M.G., L.D.B.); Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin (A.N., L.D.B.); Department of Biomedical Engineering, University of Texas, Austin (A.N., L.D.B.); Division of Cardiology, Stanford University, Palo Alto, CA (A.N.); Division of Cardiovascular Medicine, Case Western Reserve University, Cleveland, OH (A.N.); Interventional Electrophysiology, Scripps Clinic, San Diego, CA (A.N.); Dell Medical School, Austin, TX (A.N.); California Pacific Medical Center, San Francisco (A.N.); and Department of Cardiology, University of Foggia, Foggia, Italy (L.D.B.).

Background: Nonvalvular atrial fibrillation is the most common arrhythmia. Patients with nonvalvular atrial fibrillation are at increased risk of stroke; therefore, we evaluated the efficacy and safety of different approaches to prevent this major complication.

Methods And Results: We conducted electronic database searches of phase III randomized controlled trials. The groups were novel oral anticoagulants, Watchman left atrial appendage occlusion device (DEVICE), and warfarin. Efficacy outcomes were stroke or systemic embolism, and all-cause mortality. Safety outcome was major bleeding and procedure-related complications. A subgroup analysis of the elderly population was done. We used random-effects model to compare pooled outcomes and tested for heterogeneity. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for each outcome. Seven randomized controlled trials (n=73,978) were included. There was a significant difference favoring novel oral anticoagulants for systemic embolism (OR, 0.84; 95% CI, 0.72-0.97; P=0.01), all-cause mortality (OR, 0.89; 95% CI, 0.84-0.94; P<0.001), and safety outcomes (OR, 0.79; 95% CI, 0.65-0.97; P=0.026) compared with warfarin. No difference was seen between DEVICE and warfarin for efficacy end points; however, DEVICE had more complications (OR, 1.85; 95% CI, 1.14-3.01; P=0.012). In the elderly (6 randomized controlled trials, n=30,699), systemic embolism was favored with novel oral anticoagulants over warfarin (OR, 0.77; 95% CI, 0.68-0.87; P≤0.001). No evidence of significant publication bias was found.

Conclusions: Novel oral anticoagulants is superior to warfarin for stroke prevention in nonvalvular atrial fibrillation. This benefit was also observed in the elderly population. DEVICE is a reasonable noninferior alternative to warfarin for stroke prevention, but cautious use is essential given safety concerns.
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http://dx.doi.org/10.1161/CIRCEP.115.002993DOI Listing
October 2015

Robotic navigation for catheter ablation: benefits and challenges.

Expert Rev Med Devices 2015 Jul;12(4):457-69

Albert Einstein College of Medicine at Montefiore Hospital, Bronx, NY, USA.

Manual radio frequency (RF) ablation to restore a normal cardiac rhythm requires significant skill, manual dexterity and experience. In response to this, ablation methods and technologies have evolved rapidly in the past decade, including the development of remote navigation technologies. Today, two principal methods of remote navigation are available. One utilizes magnetic field vectors to navigate proprietary catheters, the other maneuvers standard catheters robotically. The main advantages of remote navigation include improved catheter stability, reduced fluoroscopy times and decreased total radiation exposure to both the patient and the operator. The main limitations include cost and longer procedure times. Remote magnetic navigation appears to have the best safety profile; however, its efficacy in creating lesions may be lower, which has been attributed to the soft-tip catheter used. Remote robotic navigation on the other hand, which uses regular catheter tips, is associated with a slightly higher overall complication rate, but higher efficacy. This article reviews the pros and cons of remote navigation for ablation of both atrial and ventricular substrates. Finally, it attempts to predict the direction of this field in the coming years.
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http://dx.doi.org/10.1586/17434440.2015.1052406DOI Listing
July 2015

Validation of PR interval length as a criterion for development of atrial fibrillation in non-Hispanic whites, African Americans and Hispanics.

J Electrocardiol 2015 Jul-Aug;48(4):703-9. Epub 2015 May 7.

Division of Cardiology, Department of Medicine, Montefiore Medical Center, Bronx, NY. Electronic address:

Background: PR interval prolongation on electrocardiogram (ECG) increases the risk of atrial fibrillation (AF). Non-Hispanic Whites are at higher risk of AF compared to African Americans and Hispanics. However, it remains unknown if prolongation of the PR interval for the development of AF varies by race/ethnicity. Therefore, we determined whether race affects the PR interval length's ability to predict AF and if the commonly used criterion of 200 ms in AF prediction models can continue to be used for non-White cohorts.

Methods: This is a retrospective epidemiological study of consecutive inpatient and outpatients. An ECG database was initially interrogated. Patients were included if their initial ECG demonstrated sinus rhythm and had two or more electrocardiograms and declared a race and/or ethnicity as non-Hispanic White, African American or Hispanic. Development of AF was stratified by race/ethnicity along varying PR intervals. Cox models controlled for age, gender, race/ethnicity, systolic blood pressure, BMI, QRS, QTc, heart rate, murmur, treatment for hypertension, heart failure and use of AV nodal blocking agents to assess PR interval's predictive ability for development of AF.

Results: 50,870 patients met inclusion criteria of which 5,199 developed AF over 3.72 mean years of follow-up. When the PR interval was separated by quantile, prolongation of the PR interval to predict AF first became significant in Hispanic and African Americans at the 92.5th quantile of 196-201 ms (HR: 1.42, 95% CI: 1.09-1.86, p=0.01; HR: 1.32, 95% CI: 1.07-1.64, p=0.01, respectively) then in non-Hispanic Whites at the 95th quantile at 203-212 ms (HR: 1.24, 95% CI: 1.24-1.53, p=0.04). For those with a PR interval above 200 ms, African Americans had a lower risk than non-Hispanic Whites to develop AF (HR: 0.80, 95% CI: 0.64-0.95, p=0.012), however, no significant difference was demonstrated in Hispanics.

Conclusions: This is the first study to validate a PR interval value of 200 ms as a criterion in African Americans and Hispanics for the development of AF. However, a value of 200 ms may be less sensitive as a predictive measure for the development of AF in African Americans compared to non-Hispanic Whites.
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http://dx.doi.org/10.1016/j.jelectrocard.2015.04.015DOI Listing
March 2016

Ablation of atrial arrhythmias in heart failure.

Heart Fail Clin 2015 Apr 26;11(2):305-17. Epub 2015 Feb 26.

Texas Cardiac Arrhythmia Institute, St David's Medical Center, 3000 North I-35, Austin, TX 78705, USA; Department of Biomedical Engineering, University of Texas, Austin, TX, USA; Division of Cardiology, Stanford University, Stanford, CA, USA; Case Western Reserve University, Cleveland, OH, USA; EP Services, California Pacific Medical Center, San Francisco, CA, USA; Interventional Electrophysiology, Scripps Clinic, San Diego, CA, USA. Electronic address:

HF and AF are on the rise and often coexist. Pharmacologic rhythm control has not been shown to improve outcomes compared with pharmacologic rate control. It is possible that the benefits of maintaining SR are offset by the adverse effects of AADs. Catheter ablation of AF offers an opportunity to achieve SR without the downside of AADs. Several studies have shown that AF ablation improves prognostic markers, including ventricular function, exercise tolerance, and perceived quality of life in HF patients. Studies addressing the impact of this treatment strategy on cardiovascular outcomes and cost-effectiveness are ongoing.
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http://dx.doi.org/10.1016/j.hfc.2014.12.008DOI Listing
April 2015

Prognostic value of automatically detected early repolarization.

Am J Cardiol 2014 Nov 13;114(9):1431-6. Epub 2014 Aug 13.

Division of Cardiology, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Electronic address:

Early repolarization associated with sudden cardiac death is based on the presence of >1-mm J-point elevations in inferior and/or lateral leads with horizontal and/or downsloping ST segments. Automated electrocardiographic readings of early repolarization (AER) obtained in clinical practice, in contrast, are defined by ST-segment elevation in addition to J-point elevation. Nonetheless, such automated readings may cause alarm. We therefore assessed the prevalence and prognostic significance of AER in 211,920 patients aged 18 to 75 years. The study was performed at a tertiary medical center serving a racially diverse urban population with a large proportion of Hispanics (43%). The first recorded electrocardiogram of each individual from 2000 to 2012 was included. Patients with ventricular paced rhythm or acute coronary syndrome at the time of acquisition were excluded from the analysis. All automated electrocardiographic interpretations were reviewed for accuracy by a board-certified cardiologist. The primary end point was death during a median follow-up of 8.0 ± 2.6 years. AER was present in 3,450 subjects (1.6%). The prevalence varied significantly with race (African-Americans 2.2%, Hispanics 1.5%, and non-Hispanic whites 0.9%, p <0.01) and gender (male 2.4% vs female 0.6%, p <0.001). In a Cox proportional hazards model controlling for age, smoking status, heart rate, QTc, systolic blood pressure, low-density lipoprotein cholesterol, body mass index, and coronary artery disease, there was no significant difference in mortality regardless of race or gender (relative risk 0.98, 95% confidence interval 0.89 to 1.07). This was true even if J waves were present. In conclusion, AER was not associated with an increased risk of death, regardless of race or gender, and should not trigger additional diagnostic testing.
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http://dx.doi.org/10.1016/j.amjcard.2014.07.077DOI Listing
November 2014

Heart rate and its variability in response to running-associations with troponin.

Med Sci Sports Exerc 2014 Aug;46(8):1624-30

1Department of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, SWEDEN; 2Department of Medicine, Montefiore Medical Center, The University Hospital of Albert Einstein School of Medicine, Bronx, NY; and 3Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, SWEDEN.

Purpose: The objective of this study is to investigate the time course of autonomic tone changes after a first-time endurance running race participation and associations with postexertional high-sensitivity troponin (hsTnT) levels in middle-aged males.

Methods: Male (n = 42) first-time long-distance running race (Lidingöloppet 30 km) participants ≥45 yr (50.5 ± 5) were examined. HR and HR variability (HRV) in the time domain (SDANN) was measured continuously from 2 d before to 4 d after the race using a wireless cardiovascular monitor that also recorded arrhythmia episodes. In addition, subjects were assessed pre- and postrace by medical history and physical examination, 12-lead ECG, blood tests including hsTnT, and echocardiography.

Results: Compared with corresponding prerace values, nighttime (2:00-4:00 a.m.) HR was significantly elevated (63.6 ± 9.4 vs 53.9 ± 8.3 bpm, P < 0.001) on the first night postrace, whereas HRV remained reduced for a median of 64 h (interquartile range, 51-102 h). A prolonged HR recovery period (r = 0.48, P = 0.005) and a larger reduction in postrace HRV (r = -0.49, P = 0.003) correlated with higher postrace hsTnT levels. The association between reduced HRV and higher hsTnT remained significant after multivariate analysis (β = -0.48, P = 0.01). No sustained ventricular arrhythmias were recorded, but atrial fibrillation occurred in two subjects.

Conclusion: Endurance running race participation caused a prolonged alteration of autonomic tone. More marked and prolonged changes were associated with higher levels of hsTnT, suggesting that the magnitude of troponin increase after strenuous exercise may reflect the magnitude of exercise-induced cardiovascular stress.
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http://dx.doi.org/10.1249/MSS.0000000000000270DOI Listing
August 2014

Early repolarization in middle-age runners: cardiovascular characteristics.

Med Sci Sports Exerc 2014 Jul;46(7):1285-92

1Department of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, SWEDEN; 2Department of Medicine, Montefiore Medical Center, University Hospital of Albert Einstein School of Medicine, Bronx, NY; and 3Department of Molecular and Clinical Medicine/Cardiology, Sahlgrenska Academy, University of Gothenburg, SWEDEN.

Purpose: This study aimed to assess the prevalence and patterns of early repolarization (ER) in middle-age long-distance runners, its relation to cardiac structure and function, and its response to strenuous physical activity.

Methods: Male first-time cross-country race participants >45 yr were assessed pre- and postrace by medical history and physical examination, 12-lead ECG, vectorcardiography, blood tests, and echocardiography. ER was defined either as ST elevation or J wave and categorized according to localization and morphology.

Results: One hundred and fifty-one subjects (50 ± 5 yr) were evaluated before the race, and 47 subjects were evaluated after the race. Altogether, 67 subjects (44%) had ER. Subjects with versus without ER had a lower resting HR (56 ± 8 vs 69 ± 9 bpm, P = 0.02), lower body mass index (24 ± 2 vs 25 ± 3 kg·m(-2), P < 0.001), higher training volume (3.0 ± 2.6 vs 2.1 ± 2.7 h·wk(-1), P = 0.03), and faster 30-km running times (194 ± 28 vs 208 ± 31 min, P = 0.01). Vectorcardiography parameters in subjects with ER showed more repolarization heterogeneity: vector gradient (QRS-T(area)) (120 ± 25 vs 92 ± 29 μVs, P < 0.001), T(area) (105 ± 18 vs 73 ± 23 μVs, P < 0.001), and T(amplitude) (0.63 ± 0.13 vs 0.53 ± 0.16 mm, P < 0.001); these parameters were inversely related to HR (r = -0.37 to -0.48, P < 0.001). ER disappeared in 15 (75%) of 20 subjects after the race.

Conclusions: ER is a common finding in middle-age male runners. This ECG pattern, regardless of morphology and localization, is associated with normal cardiac examinations including noninvasive electrophysiology, features of better physical conditioning, and disappears after strenuous exercise in most cases. These findings support that ER should be regarded as a common and training-related finding also in middle-age physically active men.
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http://dx.doi.org/10.1249/MSS.0000000000000251DOI Listing
July 2014

Preparticipation evaluation of novice, middle-age, long-distance runners.

Med Sci Sports Exerc 2013 Jan;45(1):130-7

Department of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Purpose: The purpose of this study was to assess the cardiovascular health and risk profile in middle-age men making an entry to participate for their first time in a long-distance race.

Methods: Male first-time participants, 45 yr and older, in the world's largest cross-country running race, the Lidingöloppet, were evaluated with a medical history and physical examination, European systematic coronary risk evaluation (SCORE), 12-lead ECG, echocardiography, and blood tests. Further diagnostic workup was performed when clinically indicated.

Results: Of 265 eligible runners, 153 (58%, age 51 ± 5 yr) completed the study. Although the 10-yr fatal cardiovascular event risk was low (SCORE, 1%; interquartile range, 0%-1%), mild abnormalities were common, for example, elevated blood pressure (19%), left ventricular hypertrophy (6%), and elevated LDL cholesterol (5%). ECG changes compatible with the "athlete's heart" were present in 82%, for example, sinus bradycardia (61%) and/or early repolarization (32%). ECG changes considered training unrelated were found in 24%, for example, prolonged QTc-interval (13%), left axis deviation (5.3%), and left atrial enlargement (4%). In 14 runners (9%), additional diagnostic workup was clinically motivated, and 4 runners (2%) were ultimately discouraged from vigorous exercise because of QTc intervals >500 ms (n = 2), symptomatic atrioventricular block (n = 1), and cardiac tumor (n = 1). The physician examination and the ECG identified 12 of the 14 participants requiring further evaluation.

Conclusions: Cardiovascular evaluation of middle-age men, including a physician examination and a 12-lead ECG, appears useful to identify individuals requiring further testing before vigorous exercise. The additional yield of routine echocardiography was small.
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http://dx.doi.org/10.1249/MSS.0b013e31826c5552DOI Listing
January 2013

Altered ventriculo-arterial coupling during exercise in athletes releasing biomarkers after endurance running.

Eur J Appl Physiol 2012 Dec 4;112(12):4069-79. Epub 2012 Apr 4.

Department of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Exercise can lead to release of biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), a poorly understood phenomenon proposed to especially occur with high-intensity exercise in less trained subjects. We hypothesised that haemodynamic perturbations during exercise are larger in athletes with cTnT release, and studied athletes with detectable cTnT levels after an endurance event (HIGH; n = 16; 46 ± 9 years) against matched controls whose levels were undetectable (LOW; n = 11; 44 ± 7 years). Echocardiography was performed at rest and at peak supine bicycle exercise stress. Left ventricular (LV) end-systolic elastance (E (LV) a load-independent measure of LV contractility), effective arterial elastance (E (A) a lumped index of arterial load) and end-systolic meridional wall stress were calculated from cardiac dimensions and brachial blood pressure. Efficiency of cardiac work was judged from the ventriculo-arterial coupling ratio (E (A)/E (LV): optimal range 0.5-1.0). While subgroups had similar values at rest, we found ventriculo-arterial mismatch during exercise in HIGH subjects [0.47 (0.39-0.58) vs. LOW: 0.73 (0.62-0.83); p < 0.01] due to unopposed increase in E (LV) (p < 0.05). In LOW subjects, a greater increase occurred in E (A) during exercise (+81 ± 67 % vs. HIGH: +39 ± 32 %; p = 0.02) which contributed to a maintained coupling ratio. Subjects with higher baseline NT-proBNP had greater systolic wall stress during exercise (R (2) = 0.39; p < 0.01) despite no correlation at rest (p = ns). In conclusion, athletes with exercise-induced biomarker release exhibit ventriculo-arterial mismatch during exercise, suggesting non-optimal cardiac work may contribute to this phenomenon.
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http://dx.doi.org/10.1007/s00421-012-2396-7DOI Listing
December 2012

Performance trends and cardiac biomarkers in a 30-km cross-country race, 1993-2007.

Med Sci Sports Exerc 2012 May;44(5):894-9

Karolinska Institutet, Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

Purpose: Long-distance running events enjoy increasing popularity in all ages. Whereas the health benefits of regular moderate exercise are undisputed, the net health effects of single or repeated participation in endurance events of marathon type remain to be determined. We wanted to investigate performance trends over time and the relationship between race performance and cardiac biomarker levels among participants in a large annual 30-km cross-country race.

Methods: We analyzed a database containing age, gender, run times, and previous race participation of 124,608 runners finishing the Lidingöloppet (30 km) between 1993 and 2007. In 249 male runners age ≥ 45 yr, we also performed a thorough cardiovascular examination, including measuring the cardiac biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin.

Results: Total participation increased 56% with the largest gains in younger female and older male runners. Mean run times rose from 164 ± 27 min in 1993 to 184 ± 33 min in 2007 (P < 0.001) in men and from 179 ± 26 to 203 ± 32 in women (P < 0.001) after a strong linear relationship (men, r = 0.98; women, r = 0.93). Increased run times were seen in the mean, top, and bottom quartiles as well as in the top and bottom 5% of all age and gender groups. In the substudy among 249 older male runners, not only higher body mass index, older age, and fewer previous race participations but also higher baseline NT-proBNP was independently associated with increased run time.

Conclusions: Whereas participation in the Lidingöloppet increased, fitness deteriorated over time in both genders and in all ages. In a subset of older male athletes, longer run times were associated with higher levels of NT-proBNP. The present findings may support the usefulness of preparticipation evaluation to ensure appropriate fitness and cardiovascular health in long-distance race participants.
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http://dx.doi.org/10.1249/MSS.0b013e31823cd051DOI Listing
May 2012

Effects of prolonged exercise on left ventricular mechanical synchrony in long-distance runners: importance of previous exposure to endurance races.

J Am Soc Echocardiogr 2010 Sep 5;23(9):977-84. Epub 2010 Aug 5.

Karolinska Institutet, Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

Background: Prolonged exercise has been shown to lead to elevated levels of cardiac troponin and altered cardiac function on echocardiography. It is not known if cardiac synchrony is altered by prolonged exercise. The aims of this study were to assess changes in intra-left ventricular mechanical synchrony and circulating levels of cardiac troponin following prolonged exercise and to evaluate the importance of prior exposure to endurance racing.

Methods: Forty-three male participants in a 30-km cross-country race (20 new participants at this event [median, 3 previous endurance races] age matched against 23 repeat participants [median, 31 previous endurance events]) were assessed prospectively 1 to 2 days before and 24 hours after the race using troponin T and Doppler tissue imaging analyzing the standard deviation of time to peak myocardial systolic velocity (T(s)-SD) in a six-basal, six-midventricular segment model measuring myocardial synchrony. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene was also analyzed, as I allele carriers reportedly have superior endurance performance, while the D allele predisposes to renin-angiotensin system-induced cardiac remodeling.

Results: Prerace troponin T was undetectable in all runners, and postrace levels were higher in new runners (median, 0.03 microg/L; interquartile range [IQR], 0.01-0.04 microg/L) than in repeat runners (median, 0.01 microg/L; IQR, 0.01-0.02 microg/L) (P = .03). Although new and repeat runners had similar T(s)-SD at baseline (32 msec [IQR, 22-43 msec] vs 34 msec [IQR, 29-45 msec], P = .13), dyssynchrony increased only in new runners (40 msec [IQR, 31-47 msec], P < .001; in repeat runners, median, 38 msec [IQR, 29-43 msec], P = .30; median relative difference, +13% vs +5%, P = .02). ACE genotype distribution was similar in both groups. Multivariate analysis showed that (1) a lack of prior endurance exposure; (2) more copies of the ACE D allele; and (3) lower peak systolic velocity were independent predictors of postrace dyssynchrony (P < .05 for all).

Conclusion: Prolonged exertion increased ventricular mechanical dyssynchrony in new endurance participants and in ACE D allele carriers. The long-term impact of such changes warrants future study.
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http://dx.doi.org/10.1016/j.echo.2010.06.030DOI Listing
September 2010
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