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Professor Andrew Boyle

Professor of Cardiovascular Medicine & Head of Discipline

School of Medicine and Public Health

Career Summary

Biography

Professor Andrew Boyle is a cardiologist who studies left ventricular remodeling, the process by which the heart weakens and becomes ineffective following heart attacks and with advancing age.  In particular, his research focuses on the molecular and cellular mechanisms of fibrosis and stem cell function in the heart.

Andrew received his medical degree from Monash University and then completed cardiology advanced training in Melbourne. It was during this time he noticed that early treatments for heart attack were very successful at keeping patients alive, but the late heart failure that ensued was difficult to treat. He became interested in the emerging research field of stem cell therapy for heart disease, with a view to regenerating the damaged heart muscle that occurred during a heart attack. He undertook a PhD at the University of Melbourne studying cardiac regeneration, and then moved to the US and continued this study as a fellow at Johns Hopkins University. He then joined the faculty at the University of California San Francisco, becoming Associate Professor of Medicine, where his laboratory focused on the effects of ageing on left ventricular remodeling, funded by the US National Institutes of Health. After 7 years there, he moved to the University of Newcastle and the Hunter Medical Research Institute (HMRI) where he now continues this research. Andrew has a research laboratory based at HMRI where he studies pre-clinical models of left ventricular remodeling, and he also performs clinical research at the John Hunter Hospital.

Research Expertise
Professor Andrew Boyle is a cardiologist who performs basic science, translational and clinical research. His basic science laboratory and translational research are based at HMRI, and clinical research at the John Hunter Hospital. The basic science program focuses on left ventricular remodelling, the structural and functional changes that occur after a heart attack and with age. Several preclinical models are used in the laboratory. In particular, the molecular and cellular changes of apoptosis, cardiac stem cell function and cardiac fibrosis are studied, with a view toward cardiac regeneration. The translational research program focuses on comparison between patients and preclinical models, and moving novel findings toward potential therapeutic application. The clinical research program focuses on cardiovascular outcomes following heart attacks, and testing novel therapies in these patients.

Teaching Expertise
Andrew teaches medical and biomedical science undergraduate students, as well as interns, residents, registrars and fellows in cardiology. He has considerable experience in supervising research higher degree students in his research laboratory. There are a number of available projects for research higher degree students.

Administrative Expertise


Collaborations
Andrew has ongoing research collaborations with the University of Melbourne, the University of California San Francisco, and with researchers at two centres in China.

Qualifications

  • PhD (Medicine Denistry & Health Sciences), University of Melbourne
  • Bachelor of Medicine, Bachelor of Surgery (Hons), Monash University
  • Registered Medical Practitioner, Australian Health Practitioner Regulation Agency

Keywords

  • cardiac fibrosis
  • cardiology
  • interventional cardiology
  • left ventricular remodeling
  • medical students
  • myocardial infarction

Languages

  • English (Fluent)

Fields of Research

Code Description Percentage
110201 Cardiology (incl. Cardiovascular Diseases) 100

Professional Experience

UON Appointment

Title Organisation / Department
Professor of Cardiovascular Medicine & Head of Discipline University of Newcastle
School of Medicine and Public Health
Australia

Academic appointment

Dates Title Organisation / Department
1/01/2010 -  Fellow - Society for Cardiac Angiography and Intervention Society for Cardiac Angiography and Intervention
United States
1/01/2009 -  Fellow - American Heart Association American Heart Association
United States
1/01/2008 -  Fellow - American College of Cardiology American College of Cardiology
United States
1/10/2006 - 1/12/2013 Associate Professor of Medicine University of California San Francisco
United States
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Chapter (6 outputs)

Year Citation Altmetrics Link
2017 Boyle A, 'Acute Myocardial Infarction', Current Diagnosis and Treatment in Cardiology, McGraw Hill, New York (2017)
2014 Shih HHJ, Boyle AJ, 'Aging-related changes in cellular and molecular mechanisms of postinfarction remodeling: Implications for heart failure therapy', Aging and Heart Failure: Mechanisms and Management 427-437 (2014)

© Springer Science+Business Media New York 2014. The normal course of aging is well known to result in decreased cardiac function; decreased capacity to tolerate insults, such as... [more]

© Springer Science+Business Media New York 2014. The normal course of aging is well known to result in decreased cardiac function; decreased capacity to tolerate insults, such as myocardial infarction (MI); and a higher prevalence of pathological remodeling post-MI. Recent progress in aging biology has allowed investigators to understand the effect of aging from the molecular, organelle, and cellular levels that ultimately result in organ dysfunction. In this chapter, we will review the natural course of cellular and molecular changes in the heart that predispose an aging heart toward adverse remodeling, the age-related differences in the postinfarction remodeling process, the clinical implications of aging and postinfarction remodeling, and future targets for heart failure therapy in the aged population.

DOI 10.1007/978-1-4939-0268-2
2014 Boyle AJ, Jaffe A, 'Acute Myocardial INfarction', Current Diagnosis and Treatment in Cardiology, McGraw Hill, New York (2014)
2012 Parasher PS, Boyle AJ, 'Vascular access: Arterial, venous, and ultrasound guidance', Handbook of Endovascular Peripheral Interventions 1-30 (2012)
DOI 10.1007/978-1-4614-0839-0_1
2011 Lao D, Boyle A, 'Antithrombotic Therapy for Non-ST-Elevation Acute Coronary Syndrome', Inpatient Anticoagulation 223-240 (2011)
DOI 10.1002/9781118067178.ch11
2010 Boyle AJ, McNiece IK, Hare JM, 'Mesenchymal stem cell therapy for cardiac repair.', 65-84 (2010) [C1]

Stem cell therapy for repair of damaged cardiac tissue is an attractive option to improve the health of the growing number of heart failure patients. Mesenchymal stem cells (MSCs)... [more]

Stem cell therapy for repair of damaged cardiac tissue is an attractive option to improve the health of the growing number of heart failure patients. Mesenchymal stem cells (MSCs) possess unique properties that may make them a better option for cardiac repair than other cell types. Unlike other adult stem cells, they appear to escape allorecognition by the immune system and they have immune-modulating properties, thus making it possible to consider them for use as an allogeneic cell therapy product. There is a large and growing body of preclinical and early clinical experience with MSC therapy that shows great promise in realizing the potential of stem cell therapy to effect repair of damaged cardiac tissue. This review discusses the mechanism of action of MSC therapy and summarizes the current literature in the field.

Citations Scopus - 49
Show 3 more chapters

Journal article (117 outputs)

Year Citation Altmetrics Link
2017 Shrestha U, Sciammarella M, Alhassen F, Yeghiazarians Y, Ellin J, Verdin E, et al., 'Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and

© 2015, American Society of Nuclear Cardiology. Background: The objective of this study was to measure myocardial blood flow (MBF) in humans using 99m Tc-tetrofosmin and dynamic ... [more]

© 2015, American Society of Nuclear Cardiology. Background: The objective of this study was to measure myocardial blood flow (MBF) in humans using 99m Tc-tetrofosmin and dynamic single-photon emission computed tomography (SPECT). Methods: Dynamic SPECT using 99m Tc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99m Tc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99m Tc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curve K1=F(1-Aexp(-BF)) for K 1 values estimated with 99m Tc-tefrofosmin using SPECT and MBF values estimated with 13 N-NH 3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13 N-NH 3 PET. The flow-dependent permeability surface-area product (PS) for 99m Tc-tefrofosmin was also estimated. Results: The estimated flow-extraction parameters for 99m Tc-tefrofosmin were found to be A¿=¿0.91¿±¿0.11, B¿=¿0.34¿±¿0.20 (R 2 ¿=¿0.49). The range of MBF in LAD, RCA, and LCX was 0.44-3.81¿mL/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r¿=¿0.71 (P¿ < ¿.001). However, the corresponding CFR correlation was moderate r¿=¿0.39 yet statistically significant (P¿=¿.037). The PS for 99m Tc-tefrofosmin was (0.019¿±¿0.10)*MBF¿+¿(0.32¿±¿0.16). Conclusions: Dynamic cardiac SPECT using 99m Tc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.

DOI 10.1007/s12350-015-0320-3
Citations Scopus - 2Web of Science - 6
2017 Wong R, Ahmad W, Davies A, Spratt N, Boyle A, Levi C, et al., 'Assessment of cerebral blood flow in adult patients with aortic coarctation', Cardiology in the Young, 27 1606-1613 (2017) [C1]

© Cambridge University Press 2017. Background Survival into adult life in patients with aortic coarctation is typical following surgical and catheter-based techniques to relieve ... [more]

© Cambridge University Press 2017. Background Survival into adult life in patients with aortic coarctation is typical following surgical and catheter-based techniques to relieve obstruction. Late sequelae are recognised, including stroke, hypertension, and intracerebral aneurysm formation, with the underlying mechanisms being unclear. We hypothesised that patients with a history of aortic coarctation may have abnormalities of cerebral blood flow compared with controls. Methods Patients with a history of aortic coarctation underwent assessment of cerebral vascular function. Vascular responsiveness of intracranial vessels to hypercapnia and degree of cerebral artery stiffness using Doppler-derived pulsatility indices were used. Response to photic stimuli was used to assess neurovascular coupling, which reflects endothelial function in response to neuronal activation. Patient results were compared with age- and sex-matched controls. Results A total of 13 adult patients (males=10; 77%) along with 13 controls underwent evaluation. The mean age was 36.1±3.7 years in the patient group. Patients with a ba ckground of aortic coarctation were noted to have increased pulse pressure on blood pressure assessment at baseline with increased intracranial artery stiffness compared with controls. Patients with a history of aortic coarctation had less reactive cerebral vasculature to hypercapnic stimuli and impaired neurovascular coupling compared with controls. Results Adult patients with aortic coarctation had increased intracranial artery stiffness compared with controls, in addition to cerebral vasculature showing less responsiveness to hypercapnic and photic stimuli. Further studies are required to assess the aetiology and consequences of these documented abnormalities in cerebral blood flow in terms of stroke risk, cerebral aneurysm formation, and cognitive dysfunction.

DOI 10.1017/S1047951117000920
Co-authors Rachel Wong, Christopher Levi, Peter Howe, Neil Spratt
2017 Zhang X, Khan AA, Haq EU, Rahim A, Hu D, Attia J, et al., 'Increasing mortality from ischaemic heart disease in China from 2004 to 2010: disproportionate rise in rural areas and elderly subjects. 438 million person-years follow-up.', European heart journal. Quality of care & clinical outcomes, 3 47-52 (2017) [C1]
DOI 10.1093/ehjqcco/qcw041
Co-authors John Attia, Christopher Oldmeadow
2017 de Waal K, Phad N, Collins N, Boyle A, 'Cardiac remodeling in preterm infants with prolonged exposure to a patent ductus arteriosus', Congenital Heart Disease, 12 364-372 (2017) [C1]

© 2017 Wiley Periodicals, Inc. Background: Sustained volume load due to a patent ductus arteriosus (PDA) leads to cardiac remodeling. Remodeling changes can become pathological a... [more]

© 2017 Wiley Periodicals, Inc. Background: Sustained volume load due to a patent ductus arteriosus (PDA) leads to cardiac remodeling. Remodeling changes can become pathological and are associated with cardiovascular disease progression. Data on remodeling changes in preterm infants is not available. Methods: Clinical and echocardiography data were collected in preterm infants < 30 weeks gestation on postnatal day 3 and then every 7¿14 days until closure of the ductus arteriosus. Images were analyzed using conventional techniques and speckle tracking. Remodeling changes of infants with prolonged ( > 14 days) exposure to a PDA were compared to control infants without a PDA. Results: Thirty out of 189 infants had prolonged exposure to a PDA. The left heart remodeled to a larger and more spherical shape and thus significantly increased in volume. Most changes occurred in the first 4 weeks, plateaued, and then returned to control values. Systolic function and estimates of filling pressure increased and effective arterial elastance reduced with a PDA, however contractility was unchanged. Wall thickness increased after 4 weeks of increased volume exposure. Conclusion: The preterm PDA induces early and significant remodeling of the left heart. A compensated cardiac physiology was seen with preserved systolic function, suggesting adaptive rather than pathological remodeling changes with prolonged exposure to a PDA.

DOI 10.1111/chd.12454
2017 Doherty JU, Kort S, Mehran R, Schoenhagen P, Soman P, Dehmer GJ, et al., 'ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease. A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Societ', Journal of the American Society of Echocardiography, (2017)

© 2017. This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, Ame... [more]

© 2017. This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities.Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines.A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario.The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will improve and standardize physician decision making. AUC publications reflect an ongoing effort by the American College of Cardiology to critically and systematically create, review, and categorize clinical situations where diagnostic tests and procedures are utilized by physicians caring for patients with cardiovascular diseases. The process is based on the current understanding of the technical capabilities of the imaging modalities examined.

DOI 10.1016/j.echo.2017.08.012
2017 Al-Omary MS, Davies AJ, Khan AA, McGee M, Bastian B, Leitch J, et al., 'Heart Failure Hospitalisations in the Hunter New England Area Over 10 years. A Changing Trend', HEART LUNG AND CIRCULATION, 26 627-630 (2017)
DOI 10.1016/j.hlc.2016.10.005
Co-authors John Attia
2017 Geng X, Ye J, Yeghiazarians Y, Shih H, Hwang J, Sievers R, et al., 'Myocardial Production and Release of Stem Cell Factor Following Myocardial Infarction', Journal of Biomaterials and Tissue Engineering, 7 77-82 (2017)
DOI 10.1166/jbt.2017.1543
2017 Davies AJ, Naudin C, Al-Omary M, Khan A, Oldmeadow C, Jones M, et al., 'Disparities in the incidence of acute myocardial infarction: long-term trends from the Hunter region', Internal Medicine Journal, 47 557-562 (2017) [C1]

© 2017 Royal Australasian College of Physicians Background: Trends in the incidence of acute myocardial infarction (AMI) provide important information for healthcare providers an... [more]

© 2017 Royal Australasian College of Physicians Background: Trends in the incidence of acute myocardial infarction (AMI) provide important information for healthcare providers and can allow for accurate planning of future health needs and targeted interventions in areas with an excess burden of cardiovascular disease. Aim: To investigate the regional variations in AMI incidence in the Hunter region. Methods: Incident cases of AMI identified between 1996 and 2013 from the Hunter New England Health Cardiac and Stroke Outcomes Unit were prospectively collected for this study. We calculated crude and age-adjusted incidence of AMI over an 18-year period and explored differences in remoteness, age, sex and indigenous status. Results: During 1996¿2013, a total of 15 480 cases of AMI were identified. There was a significantly higher incidence of AMI in patients from regional areas compared to patients from metropolitan areas. More importantly, while rates of AMI declined by 28% in metropolitan patients, they increased by 8% in regional patients. Males had higher rates of AMI throughout the study period than females, however there was trend over time towards a reduction in AMI incidence in males that was not seen in females. The age-adjusted incidence of AMI for indigenous patients increased by 48% from 2007 to 2013, compared to a 23% decrease in non-indigenous patients. Conclusion: Between 1996 and 2013 in the Hunter region, the adjusted incidence of AMI increased for regional patients compared to metropolitan patients with a trend towards a higher adjusted incidence of AMI in the indigenous population.

DOI 10.1111/imj.13399
Co-authors Christopher Oldmeadow
2017 Geng X, Hwang J, Ye J, Shih H, Coulter B, Naudin C, et al., 'Aging is protective against pressure overload cardiomyopathy via adaptive extracellular matrix remodeling', AMERICAN JOURNAL OF CARDIOVASCULAR DISEASE, 7 72-82 (2017) [C1]
2017 Khan AA, Fletcher PJ, Boyle AJ, 'Pre-hospital thrombolysis in ST-segment elevation myocardial infarction: a regional Australian experience.', The Medical journal of Australia, 206 369-370 (2017)
DOI 10.5694/mja16.01260
2016 Miles S, Ahmad W, Bailey A, Hatton R, Boyle A, Collins N, 'Sleep-Disordered Breathing in Patients with Pulmonary Valve Incompetence Complicating Congenital Heart Disease', Congenital Heart Disease, 11 678-682 (2016) [C1]

© 2016 Wiley Periodicals, Inc. Objective: Long standing pulmonary regurgitation results in deleterious effects on right heart size and function with late consequences of right he... [more]

© 2016 Wiley Periodicals, Inc. Objective: Long standing pulmonary regurgitation results in deleterious effects on right heart size and function with late consequences of right heart volume overload including ventricular dilatation, propensity to arrhythmia and right heart failure. As sleep disordered breathing may predispose to elevations in pulmonary vascular resistance and associated negative effects on right ventricular function, we sought to assess this in patients with underlying congenital heart disease. Design: We performed a pilot study to evaluate the incidence of sleep-disordered breathing in a patient population with a history of long standing pulmonary valve incompetence in patients with congenital heart disease using overnight oximetry. Patients. Patients with a background of tetralogy of Fallot repair or residual pulmonary incompetence following previous pulmonary valve intervention for congenital pulmonary stenosis were included. Results: Twenty-two patients underwent overnight oximetry. The mean age of the cohort was 34.3 ± 15.2 years with no patients observed to have severe underlying pulmonary hypertension. Abnormal overnight oximetry was seen in 13/22 patients (59.1%) with 2/22 (9.1%) patients considered to have severe abnormalities. Conclusions: An important proportion of patients with a background of pulmonary incompetence complicating congenital heart disease are prone to the development of sleep-disordered breathing as assessed by overnight oximetry. Further study into the prevalence and mechanisms of sleep-disordered breathing in a larger cohort are warranted.

DOI 10.1111/chd.12369
2016 de Waal K, Phad N, Collins N, Boyle A, 'Myocardial function during bradycardia events in preterm infants', Early Human Development, 98 17-21 (2016) [C1]

© 2016 Elsevier Ireland Ltd. Background Transient bradycardia episodes are common in preterm infants and often secondary to apnea. Decreased ventilation with resultant hypoxemia ... [more]

© 2016 Elsevier Ireland Ltd. Background Transient bradycardia episodes are common in preterm infants and often secondary to apnea. Decreased ventilation with resultant hypoxemia is believed to be the predominant mechanism. Sudden bradycardias without apnea are also reported, possibly due to vagal stimulation. Point of care ultrasound is used to diagnose and follow cardiovascular complications in preterm infants. Inadvertently, the operator would sometimes capture bradycardia events. This study reports on left ventricular function during such events. Methods We retrospectively reviewed our cardiac ultrasound database for bradycardia events. Apical four or three chamber images before, during and after a bradycardia event were analysed with speckle tracking software which provides systolic and diastolic parameters of myocardial motion, deformation and volume. Results Over a 2¿year period, 15 bradycardia events were noted in 14 patients with a median gestational age of 26¿weeks (range 23 to 29). Heart rate decreased by an average of 43% (171/min to 98/min). Myocardial velocity and longitudinal strain rate during the atrial component of diastole were reduced during bradycardia. Longitudinal strain during systole was increased and radial deformation was unchanged. Ventricular volumes and ejection fraction did not change. Most parameters returned to baseline values after the event. Longitudinal systolic strain rate remained lower and stroke volume was 12% higher compared to baseline. Conclusion Parameters of systolic contractility and stroke volume were maintained and parameters of atrial contractility were reduced during mild to moderate bradycardia in preterm infants. Bradycardia reduces total cardiac output with a compensatory increase detected following the event.

DOI 10.1016/j.earlhumdev.2016.05.002
2016 Khan AA, Williams T, Savage L, Stewart P, Ashraf A, Davies AJ, et al., 'Pre-hospital thrombolysis in ST-segment elevation myocardial infarction: A regional Australian experience', Medical Journal of Australia, 205 121-125 (2016) [C1]

© 2016 AMPCo Pty Ltd. Objective: The system of care in the Hunter New England Local Health District for patients with ST-segment elevation myocardial infarction (STEMI) foresees ... [more]

© 2016 AMPCo Pty Ltd. Objective: The system of care in the Hunter New England Local Health District for patients with ST-segment elevation myocardial infarction (STEMI) foresees pre-hospital thrombolysis (PHT) administered by paramedics to patients more than 60 minutes from the cardiac catheterisation laboratory (CCL), and primary percutaneous coronary intervention (PCI) at the CCL for others. We assessed the safety and effectiveness of the pre-hospital diagnosis strategy, which allocates pati ents to PHT or primary PCI according to travel time to the CCL. Design, setting and participants: Prospective, non-randomised, consecutive, single-centre case series of STEMI patients diagnosed on the basis of a pre-hospital electrocardiogram (ECG), from August 2008 to August 2013. All patients were treated at the tertiary referral hospital (John Hunter Hospital, Newcastle). Main outcome measures: The primary efficacy endpoint was all-cause mortality at 12 months; the primary safety endpoint was bleeding. Results: STEMI was diagnosed in 484 patients on the basis of pre-hospital ECG; 150 were administered PHT and 334 underwent primary PCI. The median time from first medical contact (FMC) to PHT was 35 minutes (IQR, 28¿43 min) and to balloon inflation 130 minutes (IQR, 100¿150 min). In the PHT group, 37 patients (27%) needed rescue PCI (median time, 4 h; IQR, 3¿5 h). The 12-month all-cause mortality rate was 7.0% (PHT, 6.7%; PCI, 7.2%). The incidence of major bleeding (TIMI criteria) in the PHT group was 1.3%; no patients in the primary PCI group experienced major bleeding. Conclusion: PHT can be delivered safely by paramedical staff in regional and rural Australia with good clinical outcomes.

DOI 10.5694/mja15.01336
Citations Scopus - 1Web of Science - 3
Co-authors Christopher Oldmeadow, John Attia
2015 Genet M, Lee LC, Ge L, Acevedo-Bolton G, Jeung N, Martin A, et al., 'A Novel Method for Quantifying Smooth Regional Variations in Myocardial Contractility Within an Infarcted Human Left Ventricle Based on Delay-Enhanced Magnetic Resonance Imaging', Journal of Biomechanical Engineering, 137 (2015) [C1]

Copyright © 2015 by ASME. Heart failure is increasing at an alarming rate, making it a worldwide epidemic. As the population ages and life expectancy increases, this trend is not... [more]

Copyright © 2015 by ASME. Heart failure is increasing at an alarming rate, making it a worldwide epidemic. As the population ages and life expectancy increases, this trend is not likely to change. Myocardial infarction (MI)-induced adverse left ventricular (LV) remodeling is responsible for nearly 70% of heart failure cases. The adverse remodeling process involves an extension of the border zone (BZ) adjacent to an MI, which is normally perfused but shows myofiber contractile dysfunction. To improve patient-specific modeling of cardiac mechanics, we sought to create a finite element model of the human LV with BZ and MI morphologies integrated directly from delayed-enhancement magnetic resonance (DE-MR) images. Instead of separating the LV into discrete regions (e.g., the MI, BZ, and remote regions) with each having a homogeneous myocardial material property, we assumed a functional relation between the DE-MR image pixel intensity and myocardial stiffness and contractility - we considered a linear variation of material properties as a function of DE-MR image pixel intensity, which is known to improve the accuracy of the model's response. The finite element model was then calibrated using measurements obtained from the same patient - namely, 3D strain measurements - using complementary spatial modulation of magnetization magnetic resonance (CSPAMM-MR) images. This led to an average circumferential strain error of 8.9% across all American Heart Association (AHA) segments. We demonstrate the utility of our method for quantifying smooth regional variations in myocardial contractility using cardiac DE-MR and CSPAMM-MR images acquired from a 78-yr-old woman who experienced an MI approximately 1 yr prior. We found a remote myocardial diastolic stiffness of C¯ < inf > 0 < /inf > = 0.102 kPa, and a remote myocardial contractility of T¯ < inf > max < /inf > = 146.9 kPa, which are both in the range of previously published normal human values. Moreover, we found a normalized pixel intensity range of 30% for the BZ, which is consistent with the literature. Based on these regional myocardial material properties, we used our finite element model to compute patient-specific diastolic and systolic LV myofiber stress distributions, which cannot be measured directly. One of the main driving forces for adverse LV remodeling is assumed to be an abnormally high level of ventricular wall stress, and many existing and new treatments for heart failure fundamentally attempt to normalize LV wall stress. Thus, our noninvasive method for estimating smooth regional variations in myocardial contractility should be valuable for optimizing new surgical or medical strategies to limit the chronic evolution from infarction to heart failure.

DOI 10.1115/1.4030667
Citations Scopus - 2
2015 Zhang Y, Sivakumaran P, Newcomb AE, Hernandez D, Harris N, Khanabdali R, et al., 'Cardiac Repair with a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart', Stem Cells, 33 3100-3113 (2015) [C1]

© 2015 AlphaMed Press. Cardiac resident stem cells (CRSCs) hold much promise to treat heart disease but this remains a controversial field. Here, we describe a novel population o... [more]

© 2015 AlphaMed Press. Cardiac resident stem cells (CRSCs) hold much promise to treat heart disease but this remains a controversial field. Here, we describe a novel population of CRSCs, which are positive for W8B2 antigen and were obtained from adult human atrial appendages. W8B2 + CRSCs exhibit a spindle-shaped morphology, are clonogenic and capable of self-renewal. W8B2 + CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2 + CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRa, ISL1, or WT1. W8B2 + CRSCs can differentiate into cardiovascular lineages and secrete a range of cytokines implicated in angiogenesis, chemotaxis, inflammation, extracellular matrix remodeling, cell growth, and survival. In vitro, conditioned medium collected from W8B2 + CRSCs displayed prosurvival, proangiogenic, and promigratory effects on endothelial cells, superior to that of other adult stem cells tested, and additionally promoted survival and proliferation of neonatal rat cardiomyocytes. Intramyocardial transplantation of human W8B2 + CRSCs into immunocompromised rats 1 week after myocardial infarction markedly improved cardiac function (~40% improvement in ejection fraction) and reduced fibrotic scar tissue 4 weeks after infarction. Hearts treated with W8B2 + CRSCs showed less adverse remodeling of the left ventricle, a greater number of proliferating cardiomyocytes (Ki67 + cTnT + cells) in the remote region, higher myocardial vascular density, and greater infiltration of CD163 + cells (a marker for M2 macrophages) into the border zone and scar regions. In summary, W8B2 + CRSCs are distinct from currently known CRSCs found in human hearts, and as such may be an ideal cell source to repair myocardial damage after infarction.

DOI 10.1002/stem.2101
Citations Scopus - 12Web of Science - 12
2014 Gupta V, Feng K, Cheruvu P, Boyer N, Yeghiazarians Y, Ports TA, et al., 'High femoral artery bifurcation predicts contralateral high bifurcation: implications for complex percutaneous cardiovascular procedures requiring large caliber and/or dual access.', J Invasive Cardiol, 26 409-412 (2014) [C1]
2014 Feng K, Gupta V, Terrazas E, Yeghiazarians Y, Ports T, Gregoratos G, et al., 'Trans-radial versus trans-femoral access in patients with end-stage liver disease undergoing cardiac catheterization', American Journal of Cardiovascular Disease, 4 133-139 (2014) [C1]
Citations Scopus - 2Web of Science - 2
2014 Yeghiazarians Y, Honbo N, Imhof I, Woods B, Aguilera V, Ye J, et al., 'IL-15: A novel prosurvival signaling pathway in cardiomyocytes', Journal of Cardiovascular Pharmacology, 63 406-411 (2014) [C1]

Cardiovascular disease is the leading cause of death in Western countries. A major limitation of current treatments is the inability to efficiently repair or replace dead myocardi... [more]

Cardiovascular disease is the leading cause of death in Western countries. A major limitation of current treatments is the inability to efficiently repair or replace dead myocardium. Recently, stem cell-based therapies have been explored as an avenue to circumvent current therapeutic limitations. Overall, these therapies seem to result in small improvements in the contractile function of the heart. The exact mechanism(s) of action that underlie these improvements remain unknown, and it is believed that paracrine effects play a significant role. Previously, we had reported that an extract derived from bone marrow cells, in the absence of any live cell, contained cardioprotective soluble factors. In this study, we identify IL-15 as a putative cardioprotectant within the bone marrow cells paracri ne profile. Using an in vitro culture system, we assessed the ability of IL-15 to protect cardiomyocytes under hypoxic conditions. For the first time, we have identified IL-15 receptors on the surface of cardiomyocytes and delineated the signaling system by which hypoxic cardiomyocytes may be protected from cellular death and rescued from oxidative stress with IL-15 treatment. Copyright © 2013 by Lippincott Williams & Wilkins.

DOI 10.1097/FJC.0000000000000061
Citations Scopus - 4
2014 Pandit J, Gupta V, Boyer N, Yeghiazarians Y, Ports TA, Boyle AJ, 'Patient and physician perspectives on outcomes weighting in revascularization. The POWR study', International Journal of Cardiology, (2014) [C3]
DOI 10.1016/j.ijcard.2014.08.096
2014 Velez E, Boyer N, Acevedo-Bolton G, Hope MD, Boyle A, 'CT-reconstructed three-dimensional printed models of the right subclavian artery and aorta define age-related changes and facilitate benchtop catheter testing', Journal of Invasive Cardiology, 26 E141-E144 (2014) [C1]

BACKGROUND: Severe tortuosity of the right subclavian artery (RSCA) encountered during transradial cardiac catheterization can lead to longer procedures, increased fluoroscopy tim... [more]

BACKGROUND: Severe tortuosity of the right subclavian artery (RSCA) encountered during transradial cardiac catheterization can lead to longer procedures, increased fluoroscopy time, inability to engage the coronary artery ostia, and potentially procedural failure. Increasing age is strongly correlated with subclavian tortuosity; however, the magnitude and direction of age-related changes in aortic and subclavian artery anatomy have not been defined. METHODS: Chest computed tomography (CT) angiograms of 14 patients (6 age < 45 years and 8 age =75 years) were evaluated for RSCA tortuosity. Measurements were taken along the midline of the vessel and compared to the straight distance traveled (index of tortuosity = straight distance/midline length). One normal and one tortuous subclavian were selected for three-dimensional printing and various catheters were benchtop tested on both models. RESULTS: The older group had longer (11.95 cm vs 9.6 cm; P < .01) and more tortuous subclavian arteries (lower index of tortuosity, 0.65 vs 0.76; P < .01) with more posterior unfolding (distance to most posterior aspect, 3.74 ± 0.77 cm vs 1.76 ± 0.58 cm; P < .001). Engagement of the coronary arteries of the normal model was significantly easier, with successful engagement of one or both coronaries with every catheter (n=7). Only 2 of 7 catheters (Radial Brachial and Extra Backup 3.0) were able to engage the coronary arteries in the tortuous model. CONCLUSION: Age is associated with elongation, tortuosity, and posterior unfolding of the RSCA. Three-dimensional printing of normal and tortuous arteries is feasible and shows potential to test differences between catheters.

Citations Scopus - 1Web of Science - 1
2014 Small RS, Whellan DJ, Boyle A, Sarkar S, Koehler J, Warman EN, Abraham WT, 'Implantable device diagnostics on day of discharge identify heart failure patients at increased risk for early readmission for heart failure', European Journal of Heart Failure, 16 419-425 (2014) [C1]

© 2014 The Authors. Aims We hypothesized that diagnostic data in implantable devices evaluated on the day of discharge from a heart failure hospitalization (HFH) can identify pat... [more]

© 2014 The Authors. Aims We hypothesized that diagnostic data in implantable devices evaluated on the day of discharge from a heart failure hospitalization (HFH) can identify patients at risk for HF readmission (HFR) within 30 days. Methods and results In this retrospective analysis of four studies enrolling patients with CRT devices, we identified patients with a HFH, device data on the day of discharge, and 30-day post-discharge clinical follow-up. Four diagnostic criteria were evaluated on the discharge day: (i) intrathoracic impedance > 8 O below reference impedance; (ii) AF burden > 6 h; (iii) CRT pacing < 90%; and (iv) night heart rate > 80 b.p.m. Patients were considered to have higher risk for HFR if =2 criteria were met, average risk if 1 criterion was met, and lower risk if no criteria were met. A Cox proportional hazards model was used to compare the groups. The data cohort consisted of a total of 265 HFHs in 175 patients, of which 36 (14%) were followed by HFR. On the discharge day, =2 criteria were met in 43 (16% of 265 HFHs), only 1 criterion was met in 92 (35%), and none of the four criteria were met in 130 HFHs (49%); HFR rates were 28, 16, and 7%, respectively. HFH with =2 criteria met was five times more likely to have HFR compared with HFH with no criteria met (adjusted hazard ratio 5.0; 95% confidence interval 1.9-13.5, P = 0.001). Conclusion Device-derived diagnostic criteria evaluated on the day of discharge identified patients at significantly higher risk of HFR.

DOI 10.1002/ejhf.48
Citations Scopus - 8
2014 Whitman IR, Boyle AJ, 'Extreme brachial loop', JACC: Cardiovascular Interventions, 7 334-335 (2014) [C3]
DOI 10.1016/j.jcin.2013.06.021
2013 Ye J, Hom D, Hwang J, Yeghiazarians Y, Lee R, Boyle A, 'Aging Impairs the Proliferative Capacity of Cardiospheres, Cardiac Progenitor Cells and Cardiac Fibroblasts: Implications for Cell Therapy', Journal of Clinical Medicine, 2 103-114 (2013) [C1]
DOI 10.3390/jcm2030103
Citations Scopus - 1
2013 Beyer AT, Ng R, Singh A, Zimmet J, Shunk K, Yeghiazarians Y, et al., 'Topical nitroglycerin and lidocaine to dilate the radial artery prior to transradial cardiac catheterization: A randomized, placebo-controlled, double-blind clinical trial: The PRE-DILATE Study', International Journal of Cardiology, 168 2575-2578 (2013) [C1]

Background/Objectives Transradial access (TRA) is being increasingly used for both diagnostic and interventional cardiac procedures. Use of TRA offers many advantages: decreased b... [more]

Background/Objectives Transradial access (TRA) is being increasingly used for both diagnostic and interventional cardiac procedures. Use of TRA offers many advantages: decreased bleeding, vascular complications, reduced length of hospital stay, and reduced cost. However, the small size of the radial artery limits the size of the equipment that can be used via this approach. We sought to determine whether pre-procedural administration of topical nitroglycerin and lidocaine increases the size of the radial artery. Methods Patients undergoing transradial cardiac catheterization were randomized in a double-blind fashion to a topical combination of nitroglycerin + lidocaine or placebo ointment. The primary endpoint was change in radial artery size. Secondary endpoints included radial artery spasm and radial artery patency. Results 86 patients were enrolled (43 allocated to treatment group and 43 to placebo group). Patients underwent ultrasound of the radial artery at baseline and before the catheterization. Complications were rare: one hematoma (placebo group) and one radial artery occlusion (placebo group). Baseline demographic and clinical characteristics were similar. The baseline radial artery cross-sectional area (CSA) was similar in both groups (4.95 ± 0.24 mm 2 in placebo group and 5.14 ± 0.34 mm 2 in the treatment group). However, the final CSA decreased to 4.66 ± 0.25 mm 2 in the placebo group and increased to 5.78 ± 0.38 mm 2 in the treatment group (p = 0.02), which corresponded to a decrease in CSA by - 5.6 ± 2.1% and an increase in CSA by 16.5 ± 4.2% (p < 0.0001), respectively. Conclusions Pre-procedural administration of topical mixture of nitroglycerin + lidocaine increases the size of the radial artery in patients undergoing transradial cardiac catheterization. ClinicalTrials.gov Identifier NCT01155167 © 2013 Elsevier Ireland Ltd. All rights reserved.

DOI 10.1016/j.ijcard.2013.03.048
Citations Scopus - 13
2013 Ye J, Boyle AJ, Shih H, Sievers RE, Wang ZE, Gormley M, Yeghiazarians Y, 'CD45-positive cells are not an essential component in cardiosphere formation', Cell and Tissue Research, 351 201-205 (2013) [C1]

The cardiosphere (CS) is composed of a heterogeneous population of cells, including CD45 + cells that are bone marrow (BM)-derived. However, whether the CD45 + cells are an esse... [more]

The cardiosphere (CS) is composed of a heterogeneous population of cells, including CD45 + cells that are bone marrow (BM)-derived. However, whether the CD45 + cells are an essential cell component in CS formation is unknown. The current study was undertaken to address this question. Cardiospheres (CSs) were harvested from 1-week post-myocardial infarction (MI) or non-MI hearts of C57BL/6 J mice. The process of CS formation was observed by timelapse photography. To analyze the role of BM-derived CD45 + cells in CS formation, CD45 + cells were depleted from populations of CS-forming cells by immunomagnetic beads. We recorded the number of CSs formed in culture from the same amount (10 5 ) of intact CS-forming cells, from CD45 + -cell-depleted CS-forming cells and from CD45 + cells alone (n=6-9/cell type). CS-forming cells selectively aggregated together to form CSs by 35 h after plating. The depletion of CD45 + cells from CS-forming cells actually increased the formation of CSs (67±10 CSs/10 5 cells) compared with non-depleted CS-forming cells (51±6 CSs/10 5 cells, P < 0.0001). Purified CD45 + cells from CS-forming cells did not form CSs in culture. Thus, BM-derived CD45 + cells including BM progenitors are neither necessary nor sufficient for CS formation. © 2012 Springer-Verlag Berlin Heidelberg.

DOI 10.1007/s00441-012-1511-8
Citations Scopus - 6
2013 Nazer B, Boyle A, 'Treatment of recurrent radial artery pseudoaneurysms by prolonged mechanical compression', Journal of Invasive Cardiology, 25 358-359 (2013) [C3]

As radial artery pseudoaneurysm (PA) is a rare complication of transradial catheterization, data on their management are sparse. Here, we report the case of a 77-year-old woman wh... [more]

As radial artery pseudoaneurysm (PA) is a rare complication of transradial catheterization, data on their management are sparse. Here, we report the case of a 77-year-old woman who underwent right transradial diagnostic cardiac catheterization, and subsequently developed a symptomatic PA. She underwent initial treatment with 20 minutes of mechanical compression with a Hemoband (Hemoband Corporation) with initial success. Three weeks later, she developed recurrence of her PA, and was treated with 24 hours of mechanical compression, wearing the Hemoband as an outpatient, with sustained resolution of the PA confirmed by ultrasound 1 month later, and no neurologic or further vascular complications. In addition to demonstrating that an initial PA as well as its recurrence can be treated with prolonged mechanical compression, we review the literature regarding radial artery PAs and their treatment.

Citations Scopus - 7
2013 Whellan DJ, Sarkar S, Koehler J, Small RS, Boyle A, Warman EN, Abraham WT, 'Development of a method to risk stratify patients with heart failure for 30-day readmission using implantable device diagnostics', American Journal of Cardiology, 111 79-84 (2013) [C1]

The aim of the present study was to evaluate whether diagnostic data collected after a heart failure (HF) hospitalization can identify patients with HF at risk of early readmissio... [more]

The aim of the present study was to evaluate whether diagnostic data collected after a heart failure (HF) hospitalization can identify patients with HF at risk of early readmission. The diagnostic data from cardiac resynchronization therapy defibrillator (CRT-D) devices can identify outpatient HF patients at risk of future HF events. In the present retrospective analysis of 4 studies, we identified patients with CRT-D devices, with a HF admission, and 30-day postdischarge follow-up data. The evaluation of the diagnostic data for impedance, atrial fibrillation, ventricular heart rate during atrial fibrillation, loss of CRT-D pacing, night heart rate, and heart rate variability was modeled to simulate a review of the first 7 days after discharge on the seventh day. Using a combined score created from the device parameters that were significant univariate predictors of 30-day HF readmission, 3 risk groups were created. A Cox proportional hazards model adjusting for age, gender, New York Heart Association class, and length of stay during the index hospitalization was used to compare the groups. The study cohort of 166 patients experienced a total of 254 HF hospitalizations, with 34 readmissions within 30 days. Daily impedance, high atrial fibrillation burden with poor rate control ( > 90 beat/min) or reduced CRT-D pacing ( < 90% pacing), and night heart rate > 80 beats/min were significant univariate predictors of 30-day HF readmission. Patients in the "high"-risk group for the combined diagnostic had a significantly greater risk (hazard ratio 25.4, 95% confidence interval 3.6 to 179.0, p = 0.001) compared to the "low"-risk group for 30-day readmission for HF. In conclusion, device-derived HF diagnostic criteria evaluated 7 days after discharge identified patients at significantly greater risk of a HF event within 30 days after discharge. © 2013 Elsevier Inc. All rights reserved.

DOI 10.1016/j.amjcard.2012.08.050
Citations Scopus - 13
2013 See F, Watanabe M, Kompa AR, Wang BH, Boyle AJ, Kelly DJ, et al., 'Early and delayed tranilast treatment reduces pathological fibrosis following myocardial infarction', Heart Lung and Circulation, 22 122-132 (2013) [C1]

Background: Tranilast has been shown to inhibit TGFß1-related fibrosis and organ failure in various disease models. We sought to examine the effects of tranilast on left ventricu... [more]

Background: Tranilast has been shown to inhibit TGFß1-related fibrosis and organ failure in various disease models. We sought to examine the effects of tranilast on left ventricular (LV) remodelling post-MI. Methods: Following coronary artery ligation, Sprague Dawley rats were randomised to receive tranilast (300. mg/kg/d, p.o.) or vehicle control over one of two treatment periods: (1) from 24. h until seven days post-MI, (2) from seven days to 28 days post-MI. Cardiac tissue was harvested for molecular, immunohistochemical and cell culture analyses. Results: Tranilast treatment of MI rats from 24. h until seven days post-MI reduced myocardial collagen content, a1 (I) procollagen, TGFß1 and CTGF mRNA transcripts, monocyte/macrophage infiltration and exacerbated infarct expansion compared with vehicle-treatment. Delaying the commencement of tranilast treatment to seven days post-MI attenuated myocardial fibrosis, gene expression of a1(I) procollagen, a1(III) procollagen, fibronectin, TGFß1 and CTGF mRNA transcripts, and monocyte/macrophage infiltration at 28d compared to vehicle-treatment, without detriment to infarct healing. Extended post-MI also preserved LV infarct size. In cultures of rat cardiac fibroblasts, tranilast attenuated TGFß1-stimulated fibrogenesis. Conclusion: Tranilast inhibits myocardial TGFß1 expression, fibrosis in rat post-MI and collagen production in cardiac fibroblasts. While tranilast intervention from 24. h post-MI exacerbated infarct expansion, delaying the commencement of treatment to seven days post-MI impeded LV remodelling. © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).

DOI 10.1016/j.hlc.2012.08.054
Citations Scopus - 9
2013 Natal-Hernandez L, Meadows J, Shunk KA, Boyle AJ, 'Percutaneous Retrograde Recanalization of a Chronic Total Coronary Artery Occlusion in a 7 Year Old', Cardiovascular Revascularization Medicine, 14 113-117 (2013) [C3]

The arterial switch operation for correction of transposition of the great arteries can be complicated by late stenosis or occlusion of the coronary arteries that are re-implanted... [more]

The arterial switch operation for correction of transposition of the great arteries can be complicated by late stenosis or occlusion of the coronary arteries that are re-implanted to the new aorta. We report the case of a young boy who underwent this operation as a neonate and was found to have an occluded anomalous left anterior descending artery (LAD) before age 3. Subsequent bypass surgery was complicated by anastomotic stricture and kinking of the left internal mammary artery graft to the LAD. At age 7, the LAD territory showed reversible ischemia on nuclear perfusion testing and he was referred for percutaneous coronary intervention. A combined approach with pediatric and adult interventional cardiologists resulted in successful retrograde PCI to recanalize the chronic total occlusion of the LAD. Important features of this technique in pediatric patients are discussed. © 2013 Elsevier Inc.

DOI 10.1016/j.carrev.2012.12.007
Citations Scopus - 2
2013 Boyer N, Beyer A, Gupta V, Dehghani H, Hindnavis V, Shunk K, et al., 'The effects of intra-arterial vasodilators on radial artery size and spasm: Implications for contemporary use of trans-radial access for coronary angiography and percutaneous coronary intervention', Cardiovascular Revascularization Medicine, 14 321-324 (2013) [C1]

Background: Transradial access (TRA) offers advantages including decreased vascular complications, reduced length of hospital stay, and reduced cost. The size of the radial artery... [more]

Background: Transradial access (TRA) offers advantages including decreased vascular complications, reduced length of hospital stay, and reduced cost. The size of the radial artery (RA) limits the equipment that can be used via TRA. Intra-arterial (IA) vasodilators prevent and treat RA spasm, yet are not uniformly used in TRA and their effect on the absolute size of the RA remains unknown. Methods and materials: 121 patients undergoing TRA for cardiac catheterization were included. 78 patients underwent RA angiography prior to administration of IA vasodilators ('no vasodilator' group), 43 patients underwent radial angiography after administration of an IA verapamil and nitroglycerin cocktail ('vasodilator' group). Quantitative angiography was used to compare the RA diameters. Results: Clinical characteristics were similar between the groups, except that patients in the 'no vasodilator' cohort were taller (1.67 ± 0.1. m vs. 1.73 ± 0.1. m, p = 0.002), and heavier (84.9 ± 18.2. kg vs. 75 ± 17.1. kg, p = 0.003). In the 'vasodilator' group the proximal RA diameter was larger (2.29 ± 0.47. mm vs. 2.09 ± 0.41. mm, p = 0.02) as was the narrowest segment (1.83 ± 0.56. mm vs 1.39 ± 0.43, p < 0.0001) compared to the 'no vasodilator' group. At the RA origin, 79.4% of those in the 'vasodilator' group were larger than a 6. Fr guide catheter, compared to 51.4% in the 'no vasodilator' group (p = 0.004). At the narrowest segment a higher percentage of RAs in the 'vasodilator' group were larger than a 5. Fr guide catheter (65.1% vs 26.9%, p < 0.001) and a 6. Fr catheter (34.9% vs 10.3%, p = 0.001). Conclusion: IA vasodilators increase pre-procedural RA diameter in patients undergoing cardiac catheterization via TRA. This increase in diameter has important implications for procedural planning. Summary for Table of Contents: Boyer et al. performed a blinded controlled clinical trial investigating the effects of intra-arterial vasodilators on radial artery size and spasm during cardiac catheterization. The study demonstrates that intra-arterial vasodilators significantly increased the radial artery size throughout the entire course of the vessel and significantly decreased the amount of radial artery spasm. The authors conclude that these findings support the use of intra-arterial vasodilators during cardiac catheterization and have important implications for emerging technologies such as larger bore sheathless radial procedures. © 2013 Elsevier Inc.

DOI 10.1016/j.carrev.2013.08.009
Citations Scopus - 8
2013 Boyle AJ, Hwang J, Ye J, Shih H, Jun K, Zhang Y, et al., 'The effects of aging on apoptosis following myocardial infarction', Cardiovascular Therapeutics, 31 (2013) [C1]
DOI 10.1111/1755-5922.12043
2012 Dehghani H, Boyle AJ, 'Percutaneous device closure of secundum atrial septal defect in older adults', American Journal of Cardiovascular Disease, 2 133-142 (2012) [D1]
2012 Angeli FS, Zhang Y, Sievers R, Jun K, Yim S, Boyle A, Yeghiazarians Y, 'Injection of human bone marrow and mononuclear cell extract into infarcted mouse hearts results in functional improvement', Open Cardiovascular Medicine Journal, 6 38-43 (2012) [C1]

Background: We have previously shown that mouse whole bone marrow cell (BMC) extract results in improvement of cardiac function and decreases scar size in a mouse model of myocard... [more]

Background: We have previously shown that mouse whole bone marrow cell (BMC) extract results in improvement of cardiac function and decreases scar size in a mouse model of myocardial infarction (MI), in the absence of intact cells. It is not clear if these results are translatable to extracts from human BMC (hBMC) or mononuclear cells (hMNC), which would have significant clinical implications. Methods: Male C57BL/6J (10-12 weeks old) mice were included in this study. MI was created by permanent ligation of the left anterior descending artery. Animals were randomized into three groups to receive ultrasound-guided myocardial injections with either hBMCs extract (n=6), hMNCs extract (n=8) or control with 0.5% bovine serum albumin (BSA) (n=7). Cardiac function was assessed by echocardiography at baseline, 2 and 28 days post-MI. Infarct size and vascularity was assessed at 28 days post-MI. Results: hBMC and hMNC extract preserve cardiac function and result in smaller scar size post-MI when compared with the control group. Conclusions: The current study for the first time reports that hBMC and hMNC extracts improve cardiac function post-MI in a mouse MI model. Further studies are necessary to fully address the potential clinical benefits of these therapies. © Angeli et al.; Licensee Bentham Open.

DOI 10.2174/1874192401206010038
Citations Scopus - 5
2012 Ye J, Boyle A, Shih H, Sievers RE, Zhang Y, Prasad M, et al., 'Sca-1 + cardiosphere-derived cells are enriched for isl1-expressing cardiac precursors and improve cardiac function after myocardial injury', PLoS ONE, 7 (2012) [C1]
DOI 10.1371/journal.pone.0030329
Citations Scopus - 47
2012 Nazer B, Hayward RM, Boyle AJ, 'Simultaneous thrombotic culprit lesions in two separate coronary arteries in a patient with ST-elevation myocardial infarction', European Heart Journal, 33 2622 (2012) [C3]
DOI 10.1093/eurheartj/ehs251
Citations Scopus - 2
2012 Wang TY, Masoudi FA, Messenger JC, Shunk KA, Boyle A, Brennan JM, et al., 'Percutaneous coronary intervention and drug-eluting stent use among patients =85 years of age in the United States', Journal of the American College of Cardiology, 59 105-112 (2012) [C1]

Objectives: This study assessed the comparative effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) among patients =85 years of age. Background: Despite an a... [more]

Objectives: This study assessed the comparative effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) among patients =85 years of age. Background: Despite an aging population, little is known about the comparative effectiveness of DES versus BMS among patients age =85 years undergoing percutaneous coronary intervention (PCI). Methods: We examined 471,006 PCI patients age =65 years at 947 hospitals in the National Cardiovascular Data Registry between 2004 and 2008 and linked to Medicare claims data. Long-term outcomes (median follow-up 640.8 ± 423.5 days) were compared between users of DES and BMS. Results: Patients age =85 years comprise an increasing proportion of PCIs performed among elderly subjects, yet rates of DES use declined the most in this age group. Compared with BMS, use of DES was associated with lower mortality: age =85 years, 29% versus 38% (adjusted hazard ratio [HR]: 0.80 [95% confidence interval (CI): 0.77 to 0.83] ); age 75 to 84 years, 17% versus 25% (HR: 0.77 [95% CI: 0.75 to 0.79]); and age 65 to 74 years, 10% versus 16% (HR: 0.73 [95% CI: 0.71 to 0.75] ). However, the adjusted mortality difference narrowed with increasing age (p interaction < 0.001). Conclusions: In contrast, the adjusted HR for myocardial infarction rehospitalization associated with DES use w as significantly lower with increasing age: age =85 years, 9% versus 12% (HR: 0.77 [95% CI: 0.71 to 0.83]); age 75 to 84 years, 7% versus 9% (HR: 0.81 [95% CI: 0.77 to 0.84] ); and age 65 to 74 years, 7% versus 8% (HR: 0.84 [95% CI: 0.80 to 0.88]) (p interaction < 0.001). Conclusions: In this national study of older patients undergoing PCI, declines in DES use were most pronounced among those aged =85 years, yet lower adverse-event rates associated with DES versus BMS use were observed. © 2012 by the American College of Cardiology Foundation.

DOI 10.1016/j.jacc.2011.10.853
Citations Scopus - 29
2012 Koskenvuo JW, Sievers RE, Zhang Y, Angeli FS, Lee B, Shih H, et al., 'Fractionation of mouse bone-marrow cells limits functional efficacy in non-reperfused mouse model of acute myocardial infarction', Annals of Medicine, 44 829-835 (2012) [C1]

Background and objectives. Clinical trials of bone-marrow (BM)-derived cells for therapy after acute myocardial infarct (MI) have been controversial. The most commonly used cells ... [more]

Background and objectives. Clinical trials of bone-marrow (BM)-derived cells for therapy after acute myocardial infarct (MI) have been controversial. The most commonly used cells for these trials have been mononuclear cells (MNC), obtained by fractionation of BM cells (BMCs) via different protocols. In this study, we performed a head-to-head comparison of: 1) whole BMC; 2) fractionated BM (fBM) using the commonly used Ficoll protocol; 3) the extract derived from the fBM (fBM extract) versus 4) saline (HBSS) control for treatment of acute MI. Methods. In total, 155 male C57BL/6J (10-12-week old) mice were included. Echocardiography was performed at baseline and 2 days after permanent ligation of the left anterior descending artery to induce MI. Echocardiography and histology were employed to measure outcome at 28 days post-MI. Results. Whole BMC therapy improved left ventricular ejection fraction (LVEF) post-MI, but fBM or fBM extract was not beneficial compared to control (change of LVEF of 4.9% ±4.6% (P = 0.02),-0.4% ±5.8% (P = 0.86),-2.0% ±6.2% (P = 0.97) versus-1.4% ±5.3%, respectively). The histological infarct size or numbers of arterioles or capillaries at infarct or border zone did not differ between the groups. Conclusions. Clinical studies should be performed to test whether whole BMC therapy translates into better outcome also after human MI. © 2012 Informa UK, Ltd.

DOI 10.3109/07853890.2012.672026
Citations Scopus - 4
2012 Majure DT, Hallaux M, Yeghiazarians Y, Boyle AJ, 'Topical nitroglycerin and lidocaine locally vasodilate the radial artery without affecting systemic blood pressure: A dose-finding phase I study', Journal of Critical Care, 27 9-13 (2012) [C1]
DOI 10.1016/j.jcrc.2012.04.019
Citations Scopus - 3
2012 Boyle A, 'Arrhythmias in patients with ventricular assist devices', Current Opinion in Cardiology, 27 13-18 (2012)

Purpose of Review: The numbers of patients with ongoing mechanical circulatory support (MCS) is expanding significantly. These patients continue to have significant risk of both a... [more]

Purpose of Review: The numbers of patients with ongoing mechanical circulatory support (MCS) is expanding significantly. These patients continue to have significant risk of both atrial and ventricular arrhythmias with few guidelines to suggest appropriate therapeutic strategies. Cardiologists need to understand the risks and therapeutic alternatives for the management of arrhythmias in this complex patient population. Recent Findings: Survival on MCS has steadily improved. Therefore, the duration of time during which the patients are at risk for both atrial and ventricular arrhythmias has increased. Drug-based and/or device-based therapeutic interventions are frequently required to mitigate these risks. Summary: MCS has become the mainstream therapy for the end-stage heart failure population. Atrial arrhythmias in this population can lead to decompensated heart failure or thromboembolism and therapeutic interventions include rate control, rhythm control, and adjusted anticoagulation regimens. Ventricular arrhythmias in this population can lead to decompensated heart failure, syncope, and sudden cardiac death. Therapeutic interventions include volume replenishment, antiarrhythmic drug therapy, defibrillators, and adjustment of left ventricular assist device (LVAD) parameters. MCS may also be indicated in selected patients with refractory ventricular arrhythmias. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

DOI 10.1097/HCO.0b013e32834d84fd
Citations Scopus - 23
2012 Yeghiazarians Y, Gaur M, Zhang Y, Sievers RE, Ritner C, Prasad M, et al., 'Myocardial improvement with human embryonic stem cell-derived cardiomyocytes enriched by p38MAPK inhibition', Cytotherapy, 14 223-231 (2012) [C1]

Background aims. We have shown previously that inhibition of the p38 mitogen-activated protein kinase (p38MAPK) directs the differentiation of human embryonic stem cell (hESC)-der... [more]

Background aims. We have shown previously that inhibition of the p38 mitogen-activated protein kinase (p38MAPK) directs the differentiation of human embryonic stem cell (hESC)-derived cardiomyocytes (hCM). We investigated the therapeutic benefits of intramyocardial injection of hCM differentiated from hESC by p38MAPK inhibition using closed-chest ultrasound-guided injection at a clinically relevant time post-myocardial infarction (MI) in a mouse model. Methods. MI was induced in mice and the animals treated at day 3 with: (a) hCM, (b) human fetal fibroblasts (hFF) as cell control, or (c) medium control (n = 10 animals/group). Left ventricular ejection fraction (LVEF) was evaluated post-MI prior to therapy, and at days 28 and 60 post-cell therapy. Hearts were analyzed at day 60 for infarct size, angiogenesis, cell fate and teratoma formation. Results. LVEF was improved in the hCM-treated animals compared with both hFF and medium control-treated animals at day 28 (39.03 ± 1.79% versus 27.89 ± 1.27%, P < 0.05, versus 32.90 ± 1.46%, P < 0.05, respectively), with sustained benefit until day 60. hCM therapy resulted in significantly smaller scar size, increased capillary bed area, increased number of arterioles, less native cardiomyocyte (CM) apoptosis, and increased CM proliferation compared with the other two groups. These benefits were achieved despite a very low retention rate of the injected cells at day 60, as assessed by immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). Therapy with hCM did not result in intramyocardial teratoma formation at day 60. Conclusions. This study demonstrates that hCM derived from p38MAPK-treated hESC have encouraging therapeutic potential. © 2012 Informa Healthcare.

DOI 10.3109/14653249.2011.623690
Citations Scopus - 23
2012 Crespo-Leiro MG, Zuckermann A, Bara C, Mohacsi P, Schulz U, Boyle A, et al., 'Concordance among pathologists in the second cardiac allograft rejection gene expression observational study (CARGO II)', Transplantation, 94 1172-1177 (2012) [C1]
DOI 10.1097/TP.0b013e31826e19e2
Citations Scopus - 22
2011 Koskenvuo JW, Mirsky R, Zhang Y, Helenius H, Angeli FS, de Marco T, et al., 'Evidence of diminished coronary flow in pulmonary hypertension - explaining angina pectoris in this patient group?', Clinical Physiology and Functional Imaging, 31 477-484 (2011) [C1]

Background: Many patients with pulmonary hypertension (PH) have symptoms of angina without evidence of occlusive coronary artery disease. For the first time, this study addresses ... [more]

Background: Many patients with pulmonary hypertension (PH) have symptoms of angina without evidence of occlusive coronary artery disease. For the first time, this study addresses the influence of progressively increasing pulmonary artery pressure (PAP) on left anterior descending artery flow in a rat model of PH. The role of pulmonary artery dilatation, septal wall motion abnormality, cardiac output or diastolic blood pressure in determining coronary blood flow (CBF) during PH was determined. Methods: Pulmonary hypertension was induced in 6-week-old female nude rats (n=44) using monocrotaline. Animals underwent right heart catheterization and echocardiography, and blood pressure measurement was taken at baseline, 21 and 35days. Results: A total of 103 echocardiographic studies were carried out at three fixed time points in rats with variable PAP. CBF decreased from 46·6±14·3 to 24·7 ± 12·3cms -1 (P < 0·001) over time. Pulmonary artery diameter increased from 2·30±0·19 to 2·83±0·30mm (P < 0·001), and left ventricular (LV) cardiac output decreased from 143±23 to 78±30mlmin -1 (P < 0·001). Using observed solution estimates of 0·00170 (P=0·0005) and -1·75 (P=0·006) for these variables, we calculated that CBF increased by 5·90cms -1 (15·6%, CI: 14·5-17·1%) or decreased by -4·86cms -1 (-12·9%, CI: -14·1-11·9%) for every standard deviation increase in LV cardiac output or pulmonary artery diameter, respectively. CBF decreased significantly with increasing PAP. Pulmonary artery diameter and LV cardiac output appear to be independent determinants of coronary flow in PH. Conclusions: Coronary flow reduction in murine PH has potential to be clinically meaningful and should therefore further studied in a clinical trial. © 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

DOI 10.1111/j.1475-097X.2011.01049.x
Citations Scopus - 1
2011 Zellner C, Yeghiazarians Y, Ports TA, Ursell P, Boyle AJ, 'Sterile radial artery granuloma after transradial cardiac catheterization', Cardiovascular Revascularization Medicine, 12 187-189 (2011) [C1]

Transradial cardiac catheterization has lower rates of arterial access site complications than transfemoral procedures. However, there are complications that are unique to the tra... [more]

Transradial cardiac catheterization has lower rates of arterial access site complications than transfemoral procedures. However, there are complications that are unique to the transradial route. We present the case of a sterile granuloma occurring at the site of radial arterial access as a reaction to the hydrophilic coating on the sheath. The clinical presentation was suggestive of an infected pseudoaneurysm. Awareness of this entity may help clinicians avoid unnecessary surgical procedures, as these granulomata are transient self-limiting reactions. © 2011 Elsevier Inc.

DOI 10.1016/j.carrev.2010.06.003
Citations Scopus - 8
2011 Boyle AJ, Yeghiazarians Y, Shih H, Hwang J, Ye J, Sievers R, et al., 'Myocardial production and release of MCP-1 and SDF-1 following myocardial infarction: Differences between mice and man', Journal of Translational Medicine, 9 (2011) [C1]
DOI 10.1186/1479-5876-9-150
Citations Scopus - 14
2011 Starling RC, Naka Y, Boyle AJ, 'Erratum: Results of the post-u.s. food and drug administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: A prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) (Journal of the American College of Cardiology (2011) 57 (1890-1898))', Journal of the American College of Cardiology, 58 2142 (2011)
DOI 10.1016/j.jacc.2011.09.023
Citations Scopus - 2
2011 John R, Kamdar F, Eckman P, Colvin-Adams M, Boyle A, Shumway S, et al., 'Lessons learned from experience with over 100 consecutive HeartMate II left ventricular assist devices', Annals of Thoracic Surgery, 92 1593-1600 (2011) [C1]
DOI 10.1016/j.athoracsur.2011.06.081
Citations Scopus - 55
2011 Boyle AJ, Shih H, Hwang J, Ye J, Lee B, Zhang Y, et al., 'Cardiomyopathy of aging in the mammalian heart is characterized by myocardial hypertrophy, fibrosis and a predisposition towards cardiomyocyte apoptosis and autophagy', Experimental Gerontology, 46 549-559 (2011) [C1]

Aging is associated with an increased incidence of heart failure, but the existence of an age-related cardiomyopathy remains controversial. Differences in strain, age and techniqu... [more]

Aging is associated with an increased incidence of heart failure, but the existence of an age-related cardiomyopathy remains controversial. Differences in strain, age and technique of measuring cardiac function differ between experiments, confounding the interpretation of these studies. Additionally, the structural and genetic profile at the onset of heart failure has not been extensively studied. We therefore performed serial echocardiography, which allows repeated assessment of left ventricular (LV) function, on a cohort of the same mice every 3. months as they aged and demonstrated that LV systolic dysfunction becomes apparent at 18. months of age. These aging animals had left ventricular hypertrophy and fibrosis, but did not have inducible ventricular tachyarrhythmias. Gene expression profiling of left ventricular tissue demonstrated 40 differentially expressed probesets and 36 differentially expressed gene ontology terms, largely related to inflammation and immunity. At this early stage of cardiac dysfunction, we observed increased cardiomyocyte expression of the pro-apoptotic activated caspase-3, but no actual increase in apoptosis. The aging hearts also have higher levels of anti-apoptotic and autophagic factors, which may have rendered protection from apoptosis. In conclusion, we describe the functional, structural and genetic changes in murine hearts as they first develop cardiomyopathy of aging. © 2011 Elsevier Inc.

DOI 10.1016/j.exger.2011.02.010
Citations Scopus - 54
2011 Crossley GH, Boyle A, Vitense H, Chang Y, Mead RH, 'The CONNECT (Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision) trial: The value of wireless remote monitoring with automatic clinician alerts', Journal of the American College of Cardiology, 57 1181-1189 (2011) [C1]
DOI 10.1016/j.jacc.2010.12.012
Citations Scopus - 234
2011 Bogaev RC, Pamboukian SV, Moore SA, Chen L, John R, Boyle AJ, et al., 'Comparison of outcomes in women versus men using a continuous-flow left ventricular assist device as a bridge to transplantation', Journal of Heart and Lung Transplantation, 30 515-522 (2011) [C1]
DOI 10.1016/j.healun.2010.12.009
Citations Scopus - 44
2011 Boyle AJ, Ascheim DD, Russo MJ, Kormos RL, John R, Naka Y, et al., 'Clinical outcomes for continuous-flow left ventricular assist device patients stratified by pre-operative INTERMACS classification', Journal of Heart and Lung Transplantation, 30 402-407 (2011) [C1]
DOI 10.1016/j.healun.2010.10.016
Citations Scopus - 129
2011 Mirsky R, Jahn S, Koskenvuo JW, Sievers RE, Yim SM, Ritner C, et al., 'Treatment of pulmonary arterial hypertension with circulating angiogenic cells', American Journal of Physiology - Lung Cellular and Molecular Physiology, 301 12-19 (2011) [C1]

Despite advances in the treatment of pulmonary arterial hypertension, a truly restorative therapy has not been achieved. Attention has been given to circulating angiogenic cells (... [more]

Despite advances in the treatment of pulmonary arterial hypertension, a truly restorative therapy has not been achieved. Attention has been given to circulating angiogenic cells (CACs, also termed early endothelial progenitor cells) because of their ability to home to sites of vascular injury and regenerate blood vessels. We studied the efficacy of human CAC therapy in the treatment of pulmonary arterial hypertension at two different stages of disease severity. Cells were isolated from peripheral blood and administered to nude rats on day 14 ("early") or day 21 ("late") after monocrotaline injection. The control group received monocrotaline but no cell treatment. Disease progression was assessed using right heart catheterization and echocardiography at multiple time points. Survival differences, right ventricular hypertrophy (RVH), and vascular hypertrophy were analyzed at the study endpoint. Quantitative PCR was performed to evaluate cell engraftment. Treatment with human CACs either at the early or late time points did not result in increased survival, and therapy did not prevent or reduce the severity of disease compared with control. Histological analysis of RVH and vascular muscularization showed no benefit with therapy compared with control. No detectable signal was seen of human transcript in transplanted lungs at 14 or 21 days after cell transplant. In conclusion, CAC therapy was not associated with increased survival and did not result in either clinical or histological benefits. Future studies should be geared toward either earlier therapeutic time points with varying doses of unmodified CACs or genetically modified cells as a means of delivery of factors to the pulmonary arterial circulation. © 2011 the American Physiological Society.

DOI 10.1152/ajplung.00215.2010
Citations Scopus - 15
2011 Zhang Y, Sievers RE, Prasad M, Mirsky R, Shih H, Wong ML, et al., 'Timing of bone marrow cell therapy is more important than repeated injections after myocardial infarction', Cardiovascular Pathology, 20 204-212 (2011) [C1]

Background: Bone marrow cell treatment has been proposed as a therapy for myocardial infarction, but the optimal timing and number of injections remain unknown. Methods: Myocardia... [more]

Background: Bone marrow cell treatment has been proposed as a therapy for myocardial infarction, but the optimal timing and number of injections remain unknown. Methods: Myocardial infarction was induced in mice followed by ultrasound-guided injection of mouse bone marrow cells at different time points post myocardial infarction (Days 3, 7, and 14) as monotherapy and at Days 3+7 as "double" therapy and at Days 3+7+14 as "triple" therapy. Controls received saline injections at Day 3 and Days 3+7+14. Left ventricular ejection fraction was evaluated post myocardial infarction prior to any therapy and at Day 28. Hearts were analyzed at Day 28 for infarct size and survival of donor cells. Results: Left ventricular ejection fraction decreased from 55.3±0.9% to 37.6±0.6% (P < .001) 2 days post myocardial infarction in all groups. Injection of bone marrow cells at Day 3 post myocardial infarction resulted in smaller infarct size (17.8±3.6% vs. 36.6±7.1%; P=.05) and improved LV function (left ventricular ejection fraction 40.3±2.0% vs. 31.1±8.3%; P < .05) compared to control. However, delayed therapy at Day 7 or 14 did not. Multiple injections of bone marrow cells, either double therapy or triple therapy, did not result in reduction in infarct size, but led to improvements in left ventricular ejection fraction at Day 28 compared to control (39.9±3.6% and 38.8±5.5% vs. 34.8±5.3%; all P < .05). The number of donor cells surviving at Day 28 did not correlate with improvement in left ventricular ejection fraction. Conclusions: Injection of bone marrow cells at Day 3 reduced infarct size and improved left ventricular function. Multiple injections of bone marrow cells had no additive effect. Delaying cell therapy post myocardial infarction resulted in no functional benefit at all. These results will help inform future clinical trials. © 2011 Elsevier Inc. All rights reserved.

DOI 10.1016/j.carpath.2010.06.007
Citations Scopus - 18
2010 Zellner C, Ports TA, Yeghiazarians Y, Boyle AJ, 'Sterile radial artery granuloma after transradial procedures: A unique and avoidable complication', Catheterization and Cardiovascular Interventions, 76 673-676 (2010) [C1]

Trans-radial cardiac catheterization has lower rates of arterial access site complications. Hydrophilic-coated sheaths designed specifically for trans-radial procedures have resul... [more]

Trans-radial cardiac catheterization has lower rates of arterial access site complications. Hydrophilic-coated sheaths designed specifically for trans-radial procedures have resulted in numerous reports of a foreign body reaction to retained material. Although this is a self-limited condition that should be managed expectantly, it is often confused with an infected pseudoaneurysm, resulting in unnecessary surgery. We searched the FDA MAUDE (Manufacturer and User Facility Device Experience) database to determine which brands of sheath have been associated with this complication. In addition, we performed a literature search for all reported cases of this complication. Only one brand of sheath has been associated with this condition. As trans-radial procedures become more common in the US, knowledge of such complications, which appear to be specific to the Cook radial hydrophilic-coated sheaths, is imperative for all radial interventionalists to prevent unnecessary surgical procedures. Copyright © 2010 Wiley-Liss, Inc.

DOI 10.1002/ccd.22730
Citations Scopus - 11
2010 Yong CM, Sharma M, Ochoa V, Abnousi F, Roberts J, Bass NM, et al., 'Multivessel coronary artery disease predicts mortality, length of stay, and pressor requirements after liver transplantation', Liver Transplantation, 16 1242-1248 (2010) [C1]

The optimal preoperative cardiac evaluation strategy for patients with end-stage liver disease (ESLD) undergoing liver transplantation remains unknown. Patients are frequently ref... [more]

The optimal preoperative cardiac evaluation strategy for patients with end-stage liver disease (ESLD) undergoing liver transplantation remains unknown. Patients are frequently referred for cardiac catheterization, but the effects of coronary artery disease (CAD) on posttransplant mortality are also unknown. We sought to determine the contribution of CAD and multivessel CAD in particular to posttransplant mortality. We performed a retrospective study of ESLD patients undergoing cardiac catheterization before liver transplant surgery between August 1, 2004 and August 1, 2007 to determine the effects of CAD on outcomes after transplantation. Among 83 patients who underwent left heart catheterization, 47 underwent liver transplantation during the follow-up period. Twenty-one of all ESLD patients who underwent liver transplantation (45%) had CAD. Fifteen of the transplant patients with CAD (71%) had multivessel disease. Among transplant patients, the presence of multivessel CAD (versus no CAD) was predictive of mortality (27% versus 4%, P = 0.046), increased length of stay (22 versus 15 days, P = 0.050), and postoperative pressor requirements (27% versus 4%, P = 0.029). Interestingly, neither the presence of any CAD nor the severity of stenosis in any single coronary artery predicted mortality. Furthermore, none of the traditional clinical predictors (age, gender, diabetes, creatinine, ejection fraction, and Model for End-Stage Liver Disease score) were predictive of mortality among transplant recipients. In conclusion, multivessel CAD is associated with higher mortality after liver transplantation when it is documented angiographically before transplantation, even in the absence of severe coronary artery stenosis. This study provides preliminary evidence showing that there may be significant prognostic value in coronary angiography as a part of the pretransplant workup. © 2010 American Association for the Study of Liver Diseases.

DOI 10.1002/lt.22152
Citations Scopus - 20
2010 Koskenvuo JW, Mirsky R, Zhang Y, Angeli FS, Jahn S, Alastalo TP, et al., 'A comparison of echocardiography to invasive measurement in the evaluation of pulmonary arterial hypertension in a rat model', International Journal of Cardiovascular Imaging, 26 509-518 (2010) [C1]

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resist... [more]

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigated the dia gnostic yield of echocardiographically derived TPVR and Doppler parameters of PAP in screening and measuring the severity of PAH in a rat model. Serial echocardiographic and invasive measurements were performed at baseline, 21 and 35 days after monocrotaline-induction of PAH. The most challenging echocardiographic derived TPVR measurement had good correlation with the invasive measurement (r = 0.92, P < 0.001) but also more simple and novel parameters of TPVR were found to be useful although the non-invasive TPVR measurement was feasible in only 29% of the studies due to lack of sufficient tricuspid valve regurgitation. However, echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT) and deceleration (PAD), were measurable in all animals, and correlated with invasive PAP (r = -0.74 and r = 0.75, P < 0.001 for both). Right ventricular thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001 for both). Observer variability of the invasive and non-invasive parameters was low except in tissue-Doppler derived isovolumetric relaxation time. These non-invasive parameters may be used to replace invasive measurements in detecting successful disease induction and to complement invasive data in the evaluation of PAH severity in a rat model. © The Author(s) 2010..

DOI 10.1007/s10554-010-9596-1
Citations Scopus - 34
2010 Yong CM, Boyle AJ, 'Factor Xa inhibitors in acute coronary syndromes and venous thromboembolism', Current Vascular Pharmacology, 8 5-11 (2010) [C1]

As an alternative to the inconvenient and labor intensive traditional anticoagulants, Factor Xa inhibitors may offer new options for the prevention and treatment of acute coronary... [more]

As an alternative to the inconvenient and labor intensive traditional anticoagulants, Factor Xa inhibitors may offer new options for the prevention and treatment of acute coronary syndromes (ACS) and venous thromboembolism (VTE). Fondaparinux, an indirect FXa inhibitor, has equivalent efficacy but decreased bleeding risk. It has been recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) as the preferred anticoagulant in ACS patients with higher bleeding risk managed with a noninvasive strategy. Based on the composite results of several clinical trials, fondaparinux is also recommended for VTE prevention in the setting of major orthopedic surgery. Rivaroxaban, a direct FXa inhibitor, appears to have at least equal efficacy and safety to established anticoagulants in the prevention of VTE. With advantages such as oral administration and a wide therapeutic window, it may provide a useful alternative to current anticoagulants. Ongoing studies are exploring its use in treatment of VTE and ACS, as well as prevention of stroke among patients with atrial fibrillation. In this review, we examine the key recent studies on efficacy and safety of FXa inhibitors in ACS and VTE management. © 2010 Bentham Science Publishers Ltd.

DOI 10.2174/157016110790226688
Citations Scopus - 10
2010 Shih H, Lee B, Lee RJ, Boyle AJ, 'The Aging Heart and Post-Infarction Left Ventricular Remodeling', JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 57 9-17 (2010) [C1]
DOI 10.1016/j.jacc.2010.08.623
Citations Scopus - 101Web of Science - 28
2010 boyle A, mcniece I, 'Mesenchymal Stem Cell Therapy for Cardiac Repair', Methods in Molecular Biology, 660 65 (2010)
Citations Scopus - 11
2010 Hatzistergos KE, Quevedo H, Oskouei BN, Hu Q, Feigenbaum GS, Margitich IS, et al., 'Bone Marrow Mesenchymal Stem Cells Stimulate Cardiac Stem Cell Proliferation and Differentiation', CIRCULATION RESEARCH, 107 913-+ (2010) [C1]
DOI 10.1161/CIRCRESAHA.110.222703
Citations Scopus - 404Web of Science - 376
2010 Martin JH, Connelly KA, Boyle A, Kompa A, Zhang Y, Kelly D, et al., 'Effect of Atorvastatin on Cardiac Remodelling and Mortality in Rats Following Hyperglycemia and Myocardial Infarction', INTERNATIONAL JOURNAL OF CARDIOLOGY, 143 353-360 (2010) [C1]
DOI 10.1016/j.ijcard.2009.03.098
Citations Scopus - 6Web of Science - 6
Co-authors Jen Martin
2010 John R, Liao K, Kamdar F, Eckman P, Boyle A, Colvin-Adams M, 'Effects on pre- and posttransplant pulmonary hemodynamics in patients with continuous-flow left ventricular assist devices', Journal of Thoracic and Cardiovascular Surgery, 140 447-452 (2010)

Objective: Pulsatile left ventricular assist devices have been shown to effectively reduce pulmonary hypertension in patients with end-stage heart failure. However, it remains to ... [more]

Objective: Pulsatile left ventricular assist devices have been shown to effectively reduce pulmonary hypertension in patients with end-stage heart failure. However, it remains to be seen whether newer continuous-flow left ventricular assist devices have a similar effect on pulmonary hypertension. The objective of this study was to determine whether the HeartMate II (Thoratec Corp, Pleasanton, Calif), a continuous-flow left ventricular assist device, is effective in improving pulmonary hemodynamics in the period after left ventricular assist device support and posttransplant. Methods: Fifty patients with end-stage heart failure underwent HeartMate II left ventricular assist device placement as a bridge to transplant. We evaluated their pulmonary hemodynamics with right-sided heart catheterization at baseline, after left ventricular assist device placement, and after heart transplant. Results: The mean age of patients was 53.7 ± 13.5 years. Ischemic etiology was present in 60% of the patients. After left ventricular assist device placement (mean duration, 135 ± 60 days), mean systolic and diastolic pulmonary artery pressures decreased significantly from a baseline of 55.2 ± 13.4 mm Hg and 27.3 ± 6.8 mm Hg, respectively, to 35.9 ± 10.8 mm Hg and 15.8 ± 6.5 mm Hg, respectively (P < .001). Similarly, mean pulmonary vascular resistance decreased significantly from a baseline of 3.6 ± 1.9 Woods units to 2.1 ± 0.8 Woods units (P < .001). Posttransplant pulmonary hemodynamics also remained within normal limits, even in patients with previously severe pulmonary hypertension. Conclusion: Continuous-flow left ventricular assist devices effectively improve pulmonary hemodynamics associated with end-stage heart failure. Moreover, pulmonary hemodynamics remain within normal limits in the posttransplant period, even in patients with severe pulmonary hypertension. Therefore, adequate left ventricular decompression achieved with newer left ventricular assist devices can reverse significant pulmonary hypertension in patients with end-stage heart failure, making them eligible for cardiac transplantation. Copyright © 2010 by The American Association for Thoracic Surgery.

DOI 10.1016/j.jtcvs.2010.03.006
Citations Scopus - 43
2010 Boyle AJ, 'Are ventricular assist devices underutilized?', Journal of Cardiac Surgery, 25 421-424 (2010)

A dramatic shift in the durability and reliability of ventricular assist device (VAD) therapy is taking hold due to the newer generations of continuous flow VADs that are either i... [more]

A dramatic shift in the durability and reliability of ventricular assist device (VAD) therapy is taking hold due to the newer generations of continuous flow VADs that are either in clinical trials or under consideration by the Food and Drug Administration (FDA) for commercial approval. To expand the pool of potential mechanical circulatory support (MCS) patients, device reliability will need to prove to be greatly enhanced over previous generations of VADs and functional capacity and quality of life will need to improve substantially over baseline. Improved patient selection should have the simultaneously beneficial effects of improving outcomes while expanding the MCS patient population. The critical factors determining the likelihood of expansion of the MCS field include, but are not limited to, improvements in technology and its reliability, training and education of all advanced heart failure caregivers, improving availability of MCS geographically, and a shift in patient selection to a population more likely to benefit from MCS therapy. © 2010 Wiley Periodicals, Inc.

DOI 10.1111/j.1540-8191.2010.00997.x
Citations Scopus - 4
2010 Lee S, Kamdar F, Madlon-Kay R, Boyle A, Colvin-Adams M, Pritzker M, John R, 'Effects of the HeartMate II continuous-flow left ventricular assist device on right ventricular function', Journal of Heart and Lung Transplantation, 29 209-215 (2010)

Background: Continuous-flow devices have become the standard of care for mechanical circulatory support for end-stage heart failure patients because of improved survival and durab... [more]

Background: Continuous-flow devices have become the standard of care for mechanical circulatory support for end-stage heart failure patients because of improved survival and durability. The effects of these devices, such as the HeartMate II (HMII) left ventricular assist device (LVAD), on right ventricular (RV) function have not been evaluated in detail. This study evaluated the incidence of RV failure, alterations in RV function, severity of tricuspid regurgitation (TR), and cardiac hemodynamics after HMII implantation. Methods: Echocardiograms (n = 22) and right heart catheterizations (n = 40) were performed before and after 4 to 6 months of HMII support in 40 bridge-to-transplant patients. Right heart failure was defined as the requirement for inotropes and/or nitric oxide requirement after LVAD implantation for > 14 days or the need for right-sided mechanical circulatory support. Results: Overall, RV failure after HMII implantation occurred in 2 of 40 patients (5%). Significant improvements occurred in cardiac index, with reductions in right atrial pressure, RV stroke work index, tricuspid annular motion, mean pulmonary artery pressure, and pulmonary vascular resistance after HMII support. There was a trend towards reduction in TR after LVAD support (p = 0.075). Conclusions: The incidence of RV failure after support with continuous-flow devices such as the HMII is low. The favorable effects of the HMII on cardiac hemodynamics result in improved RV function, improved right- and left-sided hemodynamic profiles, and a reduction in TR severity. These findings may have important implications for LVAD patients needing longer-term support. © 2010 International Society for Heart and Lung Transplantation.

DOI 10.1016/j.healun.2009.11.599
Citations Scopus - 66
2010 Heiss C, Jahn S, Taylor M, Real WM, Angeli FS, Wong ML, et al., 'Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease', Journal of the American College of Cardiology, 56 218-224 (2010) [C1]

Objectives: In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flav... [more]

Objectives: In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs). Background: Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function. Methods: In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64 ± 3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg] ) twice daily in random order over 30 days. Results: Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34 + /KDR + -CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: -4.2 ± 2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74 ± 32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34 + /KDR + -CACs. Conclusions: Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774). © 2010 American College of Cardiology Foundation.

DOI 10.1016/j.jacc.2010.03.039
Citations Scopus - 105
2010 Angeli FS, Amabile N, Shapiro M, Mirsky R, Bartlett L, Zhang Y, et al., 'Cytokine combination therapy with erythropoietin and granulocyte colony stimulating factor in a porcine model of acute myocardial infarction', Cardiovascular Drugs and Therapy, 24 409-420 (2010) [C1]

Purpose: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combi... [more]

Purpose: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model. Methods: MI was induced in pigs by a 90 min ball oon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI. Results: At week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41±1% vs. 33±1%, p < 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy. Conclusion: Our findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF. © The Author(s) 2010.

DOI 10.1007/s10557-010-6263-7
Citations Scopus - 9
2010 Angeli FS, Smith C, Amabile N, Shapiro M, Bartlett L, Virmani R, et al., 'Granulocyte colony stimulating factor in myocardial infarction with low ejection fraction', Cytokine, 51 278-285 (2010) [C1]

Background: We investigated the safety and efficacy of GCSF therapy in a porcine model of ischemia-reperfusion with left ventricle ejection fraction of &lt; 45% using a clinicall... [more]

Background: We investigated the safety and efficacy of GCSF therapy in a porcine model of ischemia-reperfusion with left ventricle ejection fraction of < 45% using a clinically relevant dosing and timing regimen. Methods: MI was induced in pigs by a 90. min balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either GCSF (IV bolus of 10 µg/kg at time of reperfusion, followed by SC injections of 5 µg/kg days 5-9 post-MI) or saline (control group). Inflammatory markers, bone marrow cell mobilization and LV function (echocardiog raphy and pressure-volume measurements) were assessed at baseline, 1 and 6. weeks post-MI. Histopathology was performed 6. weeks post-MI Results: GCSF therapy was associated with a significant increase in white blood cell counts. At week 6, GCSF therapy resulted in less deterioration of LVEF compared to control (38 ± 2% vs 33 ± 2%, p < 0.02) and improved wall motion score index (p < 0.05). Histopathology revealed increased vascular density (p < 0.05) and a trend toward increased areas of viable myocardium compared to control (p=0.058). Conclusion: GCSF therapy prevents further deterioration of LV function in a porcine model of MI with lower EF ( < 45%). These results support future clinical trials with GCSF in selected patients with larger MI. © 2010 Elsevier Ltd.

DOI 10.1016/j.cyto.2010.06.003
Citations Scopus - 9
2010 Angeli FS, Amabile N, Burjonroppa S, Shapiro M, Bartlett L, Zhang Y, et al., 'Prolonged Therapy With Erythropoietin is Safe and Prevents Deterioration of Left Ventricular Systolic Function in a Porcine Model of Myocardial Infarction', Journal of Cardiac Failure, 16 579-589 (2010) [C1]

Background: Erythropoietin (EPO) has generated interest as a novel therapy after myocardial infarction (MI), but the safety and efficacy of prolonged therapy have not been studied... [more]

Background: Erythropoietin (EPO) has generated interest as a novel therapy after myocardial infarction (MI), but the safety and efficacy of prolonged therapy have not been studied in a large animal model of reperfused MI. Methods and Results: MI was induced in pigs by a 90-minute balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either EPO or saline (control group). Inflammatory markers, bone marrow cell mobilization, and left ventricular function (by both echocardiography and pressure-volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. EPO therapy was associated with a significant increase in hemoglobin and mononuclear counts. D-dimer and C-reactive protein levels did not differ between groups. At week 6, EPO therapy prevented further deterioration of left ventricular ejection fraction (39 ± 2% vs. 33 ± 1%, P < .01) and improved wall motion score index (P < .02). Histopathology revealed increased areas of viable myocardium, vascular density, and capillary-to-myocyte ratio in the EPO therapy compared with the control (all P < .05). Conclusion: Prolonged EPO therapy after MI in a large animal model is safe and leads to an increase in viable myocardium, increased vascular density, and prevents further deterioration of left ventricular function. These results support future clinical studies in post-MI patients. © 2010 Elsevier Inc. All rights reserved.

DOI 10.1016/j.cardfail.2010.02.008
Citations Scopus - 8
2010 Yeghiazarians Y, Khan M, Angeli FS, Zhang Y, Jahn S, Prasad M, et al., 'Cytokine combination therapy with long-acting erythropoietin and granulocyte colony stimulating factor improves cardiac function but is not superior than monotherapy in a mouse model of acute myocardial infarction', Journal of Cardiac Failure, 16 669-678 (2010) [C1]

Background: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) are potential novel therapies after myocardial infarction (MI). We first established the optimal ... [more]

Background: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) are potential novel therapies after myocardial infarction (MI). We first established the optimal and clinically applicable dosages of these drugs in mobilizing hematopoietic stem cells (HSC), and then tested the efficacy of monotherapy and combination therapy post-MI. Methods and Results: Optimal doses were established in enhanced green fluorescent protein (eGFP) + chimeric mice (n = 30). Next, mice underwent MI and randomized into 4 groups (n = 18/group): 1) GCSF; 2) EPO; 3) EPO+GCSF; and 4) control. Left ventricular (LV) function was analyzed pre-MI, a t 4 hours and at 28 days post-MI. Histological assessment of infarct size, blood vessels, apoptotic cardiomyocytes, and engraftment of eGFP+ mobilized cells were analyzed at day 28. LV function in the control group continued to deteriorate, whereas all treatments showed stabilization. The treatment groups resulted in less scarring, increased numbers of mobilized cells to the infarct border zone (BZ), and a reduction in the number of apoptotic cardiomyocytes. Both EPO groups had significantly more capillaries and arterioles at the BZ. Conclusion: We have established the optimal doses for EPO and GCSF in mobilizing HSC from the bone marrow and demonstrated that therapy with these agents, either as monotherapy or combination therapy, led to improvement of cardiac function post-MI. Combination therapy does not seem to have additive benefit over monotherapy in this model. © 2010 Elsevier Inc. All rights reserved.

DOI 10.1016/j.cardfail.2010.03.008
Citations Scopus - 13
2009 Yeghiazarians Y, Zhang Y, Prasad M, Shih H, Saini SA, Takagawa J, et al., 'Injection of bone marrow cell extract into infarcted hearts results in functional improvement comparable to intact cell therapy', Molecular Therapy, 17 1250-1256 (2009) [C1]

We compared therapeutic benefits of intramyocardial injection of unfractionated bone marrow cells (BMCs) versus BMC extract as treatments for myocardial infarction (MI), using clo... [more]

We compared therapeutic benefits of intramyocardial injection of unfractionated bone marrow cells (BMCs) versus BMC extract as treatments for myocardial infarction (MI), using closed-chest ultrasound-guided injection at a clinically relevant time post-MI. MI was induced in mice and the animals treated at day 3 with either: (i) BMCs from green fluorescent protein (GFP)-expressing mice (n = 14), (ii) BMC extract (n = 14), or (iii) saline control (n = 14). Six animals per group were used for histology at day 6 and the rest followed to day 28 for functional analysis. Ejection fraction was similarly improved in the BMC and extract groups versus control (40.6 ± 3.4 and 39.1 ± 2.9% versus 33.2 ± 5.0%, P < 0.05) with smaller scar sizes. At day 6 but not day 28, both therapies led to significantly higher capillary area and number of arterioles versus control. At day 6, BMCs increased the number of cycling cardiomyocytes (CMs) versus control whereas extract therapy resulted in significant reduction in the number of apoptotic CMs at the border zone (BZ) versus control. Intracellular components within BMCs can enhance vascularity, reduce infarct size, improve cardiac function, and influence CM apoptosis and cycling early after therapy following MI. Intact cells are not necessary and death of implanted cells may be a major component of the benefit.

DOI 10.1038/mt.2009.85
Citations Scopus - 57
2009 Angeli FS, Shapiro M, Amabile N, Orcino G, Smith CS, Tacy T, et al., 'Left ventricular remodeling after myocardial infarction: Characterization of a swine model on ß-blocker therapy', Comparative Medicine, 59 272-279 (2009) [C1]

Current guidelines recommend ß blockers for patients after myocardial infarction (MI). Novel therapies for heart failure should be tested in combination with this medication befo... [more]

Current guidelines recommend ß blockers for patients after myocardial infarction (MI). Novel therapies for heart failure should be tested in combination with this medication before entering clinical trials. In this methodologic study, we sought to describe the time course of systolic and diastolic parameters of cardiac performance over a 6-wk period in closed-chest model of swine MI treated with a ß blocker. Myocardial infarction in pigs (n = 10) was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Echocardiography and pressure-volume data were collected before and at 1 and 6 wk after MI; histopathology was assessed at 6 wk. Left-ventricular (LV) volume increased significantly over 6 wk, with significant decreases in ejection fraction, wall motion index, stroke work, rate of pressure development (dP/dt max ), preload recruitable stroke work, and mechanical efficiency. Impairment of diastolic function was manifested by a significant increase in the exponential ß coefficient of the LV end-diastolic pressure-volume relation and reduction of LV pressure decay. At 6 wk, histopathologic analysis showed that the size of the infarct area was 16.3% ± 4.4%, and the LV mass and myocyte cross-sectional area in both the infarct border and remote zones were increased compared with those of noninfarcted pigs (n = 5). These findings suggest a dynamic pattern of remodeling over time in a closed-chest ischemia-reperfusion swine model of acute MI on ß-blocker therapy and may guide future studies. Copyright 2009 by the American Association for Laboratory Animal Science.

Citations Scopus - 14
2009 Sharma M, Yong C, Majure D, Zellner C, Roberts JP, Bass NM, et al., 'Safety of Cardiac Catheterization in Patients With End-Stage Liver Disease Awaiting Liver Transplantation', American Journal of Cardiology, 103 742-746 (2009) [C1]

Patients with end-stage liver disease (ESLD) are predisposed to bleeding complications due to thrombocytopenia, reduced synthesis of coagulation factors, and increased fibrinolyti... [more]

Patients with end-stage liver disease (ESLD) are predisposed to bleeding complications due to thrombocytopenia, reduced synthesis of coagulation factors, and increased fibrinolytic activity. The exact incidence of vascular access site and bleeding complications related to cardiac catheterization in this group remains unknown. Eighty-eight consecutive patients with ESLD who underwent left-sided cardiac catheterization from August 2004 to February 2007 were identified. Eighty-one patients without known liver disease matched for age, gender, and body mass index who underwent left-sided cardiac catheterization during the same period were chosen as the control group. Vascular complications were defined as hematoma > 5 cm, pseudoaneurysm, arteriovenous fistula, or retroperitoneal bleeding. Patients with ESLD had lower baseline mean hematocrit (32.3 ± 6.0% vs 39.2 ± 6.2%, p < 0.001) and mean platelet count (90.1 ± 66.3 vs 236.1 ± 77.1 × 10 9 /L, p < 0.001) compared with controls. They also had higher mean serum creatinine (1.9 ± 1.7 vs 1.2 ± 0.8 mg/dl, p = 0.002) and mean international normalized ratio (1.6 ± 0.7 vs 1.1 ± 0.2, p < 0.001). There were more complicated pseudoaneurysms in the patients with liver failure (5.7% [5 of 88]), compared with 0% in controls (p = 0.029). Patients with ESLD had lower starting hemoglobin levels and greater reductions in hemoglobin after cardiac catheterization, resulting in greater need for packed red blood cell transfusion (16% vs 4%, p = 0.008), fresh frozen plasma (51.7% vs 1.2%, p < 0.001), and platelet transfusions (48.3% vs 1.2%, p < 0.001). Major bleeding was higher in the ESLD group (14.8% vs 3.7%, p = 0.014), driven mainly by the need for blood transfusion. In conclusion, despite severe coagulopathy, left-sided cardiac catheterization may be performed safely in this patient population, with correction of coagulopathy and meticulous attention to procedural technique. © 2009 Elsevier Inc. All rights reserved.

DOI 10.1016/j.amjcard.2008.10.037
Citations Scopus - 39
2009 Crow S, John R, Boyle A, Shumway S, Liao K, Colvin-Adams M, et al., 'Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices', Journal of Thoracic and Cardiovascular Surgery, 137 208-215 (2009)

Objective: Pulsatile and nonpulsatile left ventricular assist devices are effective in managing congestive heart failure. Despite early evidence for clinical efficacy, the long-te... [more]

Objective: Pulsatile and nonpulsatile left ventricular assist devices are effective in managing congestive heart failure. Despite early evidence for clinical efficacy, the long-term impact of nonpulsatile flow on end-organ function remains to be determined. Our goal was to compare rates of gastrointestinal bleeding in nonpulsatile and pulsatile device recipients. Methods: In a retrospective review of 101 left ventricular assist device recipients (55 nonpulsatile, 46 pulsatile) from October 31, 2003, to June 1, 2007, at a single center, gastrointestinal bleeding was defined as guaiac-positive stool with hemoglobin drop requiring transfusion of at least 2 units of packed red blood cells. To assess bleeding risk outside the initial postoperative course, any patients with a device in place for 15 days or less was excluded. Results: Twelve nonpulsatile and 3 pulsatile left ventricular assist device recipients had gastrointestinal bleeding 16 days or longer after device implantation. The event rates were 63 events/100 patient-years for nonpulsatile devices and 6.8 events/100 patient-years for pulsatile devices (P = .0004). This difference persisted for bleeding occurring 31 days or longer after device implantation, with 46.5 events/100 patient-years for nonpulsatile devices versus 4.7 events/100 patient-years for pulsatile devices (P = .0028). Mortalities were similar between groups (15% nonpulsatile vs 17% pulsatile, P = .6965). Conclusion: Patients with nonpulsatile left ventricular assist devices appear to have a higher rate of gastrointestinal bleeding events than do pulsatile left ventricular assist device recipients. Further prospective evaluation is needed to determine potential etiologies and strategies for reducing gastrointestinal bleeding in this population. © 2009 The American Association for Thoracic Surgery.

DOI 10.1016/j.jtcvs.2008.07.032
Citations Scopus - 245
2009 Lietz K, Brown K, Ali SS, Colvin-Adams M, Boyle AJ, Anderson D, et al., 'The role of cerebral hyperperfusion in postoperative neurologic dysfunction after left ventricular assist device implantation for end-stage heart failure', Journal of Thoracic and Cardiovascular Surgery, 137 1012-1019 (2009)

Objective: Cerebral hyperperfusion is a life-threatening syndrome that can occur in patients with chronically hypoperfused cerebral vasculature whose normal cerebral circulation w... [more]

Objective: Cerebral hyperperfusion is a life-threatening syndrome that can occur in patients with chronically hypoperfused cerebral vasculature whose normal cerebral circulation was re-established after carotid endarterectomy or angioplasty. We sought to determine whether the abrupt restoration of perfusion to the brain after left ventricular assist device (LVAD) implantation produced similar syndromes. Methods: We studied the role of increased systemic flow after LVAD implantation on neurologic dysfunction in 69 consecutive HeartMate XVE LVAD (Thoratec, Pleasanton, Calif) recipients from October 2001 through June 2006. Neurologic dysfunction was defined as postoperative permanent or transient central change in neurologic status, including confusion, focal neurologic deficits, visual changes, seizures, or coma for more than 24 hours within 30 days after LVAD implantation. Results: We found that 19 (27.5%) patients had neurologic dysfunction, including encephalopathy (n = 11), coma (n = 3), and other complications (n = 5). The multivariate analysis showed that an increase in cardiac index from the preoperative baseline value (relative risk, 1.33 per 25% cardiac index increase; P = .01) and a previous coronary bypass operation (relative risk, 4.53; P = .02) were the only independent predictors of neurologic dysfunction. Reduction of left ventricular assist device flow in 16 of the 19 symptomatic patients led to improvement of symptoms in 14 (87%) patients. Conclusions: Our findings showed that normal flow might overwhelm cerebral autoregulation in patients with severe heart failure, suggesting that cerebral hyperperfusion is possible in recipients of mechanical circulatory support with neurologic dysfunction. © 2009 The American Association for Thoracic Surgery.

DOI 10.1016/j.jtcvs.2008.11.034
Citations Scopus - 25
2009 Kamdar F, Boyle A, Liao K, Colvin-adams M, Joyce L, John R, 'Effects of Centrifugal, Axial, and Pulsatile Left Ventricular Assist Device Support on End-Organ Function in Heart Failure Patients', Journal of Heart and Lung Transplantation, 28 352-359 (2009)

Purpose: Newer continuous-flow left ventricular assist devices (LVAD) have the advantage of smaller size and increased durability. Questions remain regarding the safety and effect... [more]

Purpose: Newer continuous-flow left ventricular assist devices (LVAD) have the advantage of smaller size and increased durability. Questions remain regarding the safety and effects of long-term nonpulsatile flow, despite some animal and human studies showing that end-organ function is well maintained with pulsatile or axial-flow devices. This study investigated whether centrifugal devices have similar effects on end-organ function. Methods: All patients who underwent LVAD implantation as bridge-to-transplant (BTT) therapy from January 2004 through May 2007 were reviewed. Excluded were patients on biventricular support, destination therapy, temporary support, and patients who died within 30 days after LVAD implantation. The centrifugal device was the VentrAssist (Ventracor Ltd, Sydney, Australia); axial, the HeartMate II; and pulsatile, the HeartMate XVE (Thoratec Corp, Pleasanton, CA). Results: During the study, 10 VentrAssist, 30 HeartMate II, and 18 HeartMate XVE devices were implanted. Among the 3 groups, age, gender, weight, duration of LVAD support, and cause of heart failure were comparable. No significant differences were found between groups with respect to baseline renal function, hepatic function, or hematologic function. At 1 and 3 months of follow-up, renal and hepatic function either improved or remained within normal limits in all groups. Conclusions: Centrifugal, axial, and pulsatile LVADs all provide adequate circulatory support to maintain appropriate end-organ function in patients with end-stage heart failure. The advantages of the newer continuous-flow devices can be safely applied to an increasing number of patients. Long-term studies ( > 1 year) are needed to assess effects on end-organ function with continuous-flow devices, which may have important implications for use as destination therapy. © 2009 International Society for Heart and Lung Transplantation.

DOI 10.1016/j.healun.2009.01.005
Citations Scopus - 105
2009 Ali SS, Olinger CC, Sobotka PA, Dahle TGA, Bunte MC, Blake D, Boyle AJ, 'Loop diuretics can cause clinical natriuretic failure: A prescription for volume expansion', Congestive Heart Failure, 15 1-4 (2009)

Ultrafiltration enhances volume removal and weight reduction vs diuretics. However, their differential impact on total body sodium, potassium, and magnesium has not been described... [more]

Ultrafiltration enhances volume removal and weight reduction vs diuretics. However, their differential impact on total body sodium, potassium, and magnesium has not been described. Fifteen patients with congestion despite diuretic therapy had urine electrolytes measured after a diuretic dose. Ultrafiltration was initiated and ultrafiltrate electrolytes were measured. The urine sodium after diuretics (60±47 mmol/L) was less than in the ultrafiltrate (134±8.0 mmol/L) (P=.000025). The urine potassium level after diuretics (41±23 mmol/L) was greater than in the ultrafiltrate (3.7±0.6 mmol/L) (P=.000017). The urine magnesium level after diuretics (5.2±3.1 mg/dL) was greater than in the ultrafiltrate (2.9±0.7 mg/dL) (P=.017). In acute decompensated heart failure patients with congestion despite diuretic therapy, diuretics are poor natriuretics and cause significant potassium and magnesium loss. Ultrafiltration extracts more sodium while sparing potassium and magnesium. The sustained clinical benefits of ultrafiltration compared with diuretics may be partly related to their disparate effects on total body sodium, potassium, and magnesium, in addition to their differential efficacy of volume removal. © 2009 Wiley Periodicals, Inc.

DOI 10.1111/j.1751-7133.2008.00037.x
Citations Scopus - 47
2009 Boyle A, 'Current status of cardiac transplantation and mechanical circulatory support', Current Heart Failure Reports, 6 28-33 (2009)

Cardiac transplantation and mechanical circulatory support are possible options for improving survival and quality of life in patients with isolated cardiac disease and end-stage ... [more]

Cardiac transplantation and mechanical circulatory support are possible options for improving survival and quality of life in patients with isolated cardiac disease and end-stage heart failure. Transplantation is limited by donor availability but has a median survival of 10 years. Post-transplant immunosuppression is often transplant center dependent, but a tacrolimus and mycophenolate mofetil-based regimen may be preferred. Sirolimus may reduce the progression rate of transplant vasculopathy. There has been a trend toward continuous-flow left ventricular assist devices because of their increased durability and reduced size. A variety of surgical and percutaneous ventricular assist devices may be used as a bridge to decision on a patient's candidacy for transplantation. Mechanical circulatory support as destination therapy has not been widely implemented because of poor device durability, but this is expected to change with newer devices. Mechanical circulatory support as a bridge to myocardial recovery has been successful only in a few patients. © Current Medicine Group, LLC 2009.

DOI 10.1007/s11897-009-0006-8
Citations Scopus - 19
2009 John R, Boyle A, Pagani F, Miller L, 'Physiologic and pathologic changes in patients with continuous-flow ventricular assist devices', Journal of Cardiovascular Translational Research, 2 154-158 (2009)

The clinical use of the newer continuous-flow pumps for mechanical circulatory support have resulted in superior outcomes including significantly reduced complication rates with i... [more]

The clinical use of the newer continuous-flow pumps for mechanical circulatory support have resulted in superior outcomes including significantly reduced complication rates with improved durability over first generation pulsatile design pumps. However, as with all new technology, the newer LVADs have introduced a different set of management issues, as well as a unique risk profile into the mechanical circulatory support arena that were previously absent or unimportant with pulsatile LVADs. These include the effects of continuous flow on the systemic circulation and end-organ function, risk of thromboembolism, and pump thrombosis related to contact bearings in the blood path, the possible increased incidence of gastrointestinal bleeding, and ventricular arrhythmias, as well as alterations in the unloading characteristics of continuous-flow devices. This manuscript overviews the physiologic and pathologic effects that are associated with continuous-flow pumps and their unique management issues and complications. © 2009 Springer Science+Business Media, LLC.

DOI 10.1007/s12265-009-9092-y
Citations Scopus - 24
2008 Zellner C, Boyle A, Yeghiazarians Y, 'Magnesium sulfate for transradial cardiac catheterization: Teaching an old dog new tricks', Journal of Invasive Cardiology, 20 543-544 (2008) [C3]
Citations Scopus - 2
2008 Sharma M, Sakhuja R, Teitel D, Boyle A, 'Percutaneous arterial closure for inadvertent cannulation of the subclavian artery - A call for caution', Journal of Invasive Cardiology, 20 (2008) [C1]
Citations Scopus - 5
2008 Schuleri KH, Boyle AJ, Centola M, Amado LC, Evers R, Zimmet JM, et al., 'The Adult Gottingen Minipig as a Model for Chronic Heart Failure After Myocardial Infarction: Focus on Cardiovascular Imaging and Regenerative Therapies', COMPARATIVE MEDICINE, 58 568-579 (2008) [C1]
Citations Scopus - 35Web of Science - 37
2008 Schuleri KH, Amado LC, Boyle AJ, Centola M, Saliaris AP, Gutman MR, et al., 'Early improvement in cardiac tissue perfusion due to mesenchymal stem cells', American Journal of Physiology - Heart and Circulatory Physiology, 294 (2008) [C1]

The underlying mechanism(s) of improved left ventricular function (LV) due to mesenchymal stem cell (MSC) administration after myocardial infarction (MI) remains highly controvers... [more]

The underlying mechanism(s) of improved left ventricular function (LV) due to mesenchymal stem cell (MSC) administration after myocardial infarction (MI) remains highly controversial. Myocardial regeneration and neovascularization, which leads to increased tissue perfusion, are proposed mechanisms. Here we demonstrate that delivery of MSCs 3 days after MI increased tissue perfusion in a manner that preceded improved LV function in a porcine model. MI was induced in pigs by 60-min occlusion of the left anterior descending coronary artery, followed by reperfusion. Pigs were assigned to receive intramyocardial injection of allogeneic MSCs (200 million, ~15 injections) (n = 10), placebo (n = 6), or no intervention (n = 8). Resting myocardial blood flow (MBF) was serially assessed by first-pass perfusion magnetic resonance imaging (MRI) over an 8-wk period. Over the first week, resting MBF in the infarct area of MSC-treated pigs increased compared with placebo-injected and untreated animals [0.17 ± 0.03, 0.09 ± 0.01, and 0.08 ± 0.01, respectively, signal intensity ratio of MI to left ventricular blood pool (LVBP); P < 0.01 vs. placebo, P < 0.01 vs. nontreated]. In contrast, the signal intensity ratios of the three groups were indistinguishable at weeks 4 and 8. However, MSC-treated animals showed larger, more mature vessels and less apoptosis in the infarct zones and improved regional and global LV function at week 8. Together these findings suggest that an early increase in tissue perfusion precedes improvements in LV function and a reduction in apoptosis in MSC-treated hearts. Cardiac MRI-based measures of blood flow may be a useful tool to predict a successful myocardial regenerative process after MSC treatment. Copyright © 2008 the American Physiological Society.

DOI 10.1152/ajpheart.00762.2007
Citations Scopus - 114
2008 Crossley G, Boyle A, Vitense H, Sherfesee L, Mead RH, 'Trial design of the clinical evaluation of remote notification to reduce time to clinical decision: The Clinical evaluation Of remote NotificatioN to rEduCe Time to clinical decision (CONNECT) study', American Heart Journal, 156 840-846 (2008)

Background: Indications for implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy defibrillators have greatly expanded in the last 5 years, encompas... [more]

Background: Indications for implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy defibrillators have greatly expanded in the last 5 years, encompassing a wider variety of patients with a multitude of comorbidities. To meet the needs of these patients, the managing clinicians need to streamline their follow-up care. New ICD/cardiac resynchronization therapy defibrillators provide enhanced device status and disease progression remote monitoring capabilities that support more comprehensive and efficient follow-ups. In addition, this monitoring between follow-ups is likely to impact health care utilization. Methods and Results: The Clinical evaluation Of remote NotificatioN to rEduCe Time to clinical decision (CONNECT) study will randomize approximately 2,000 patients implanted with an ICD with or without CRT capabilities from 150 sites in the United States to remote monitoring versus standard in-office care. This study will evaluate the time from clinical event to clinical decision in response to the event, as well as the associated impact on health care utilization and quality of life. Patients monitored remotely will be provided a home monitor for transmitting device diagnostics to the clinician's office. These devices will use wireless telemetry, allowing the automatic transmission of diagnostics to the office without the need for patient intervention. Patients receiving in-office care will be followed in the office at a fixed schedule and without remote monitoring. All patients will be followed for 15 months postimplant. Conclusion: The CONNECT study is evaluating the impact of remote monitoring and early notification using wireless telemetry on the time to clinical decisions, the allocation of health care utilization, and quality of life. Results from this study are expected mid-2009. © 2008 Mosby, Inc. All rights reserved.

DOI 10.1016/j.ahj.2008.06.028
Citations Scopus - 24
2008 John R, Kamdar F, Liao K, Colvin-Adams M, Boyle A, Joyce L, 'Improved Survival and Decreasing Incidence of Adverse Events With the HeartMate II Left Ventricular Assist Device as Bridge-to-Transplant Therapy', Annals of Thoracic Surgery, 86 1227-1235 (2008)

Background: Pulsatile left ventricular assist devices (LVADs) are effective as bridge-to-transplant therapy, but they are limited by their large size and lack of durability. Small... [more]

Background: Pulsatile left ventricular assist devices (LVADs) are effective as bridge-to-transplant therapy, but they are limited by their large size and lack of durability. Smaller, more durable, continuous flow devices such as the HeartMate II LVAD are increasingly being used. The aim of this study is to report our single-center experience with this device as bridge-to-transplant therapy. Methods: Overall, 47 patients received HeartMate II LVADs at our center from June 2005 to July 2007; 32 as bridge to transplant, 7 as destination therapy, and 8 as exchange therapy for a failed HeartMate XVE. We reviewed our experience with the device as bridge-to-transplant therapy and report on patient survival and adverse events. Results: The mean age of the bridge-to-transplant patients was 50.75 ± 13.78 years; 10 (31.3%) were female. The cause of the underlying disease was ischemic in 18 patients (56.3%), idiopathic in 11 (34.4%), myocarditis in 1 (3.1%), postpartum cardiomyopathy in 1 (3.1%), and congenital heart disease in 1 (3.1%). The mean duration of HeartMate II support was 193.2 ± 139.9 days. At 30 days after HeartMate II placement, the patient survival was 96.9% by Kaplan-Meier analysis; at 6 months (alive or transplanted), 86.9%. Major adverse events included bleeding requiring reexploration in 5 patients (15.6%), right ventricular failure requiring right ventricular assist device support in 2 (6.3%), LVAD-related infections in 4 (12.5%), neurologic or thromboembolic events in 2 (6.3%), and gastrointestinal bleeding in 5 (15.6%). We noted one serious device malfunction (3.1%) resulting in the patient's death; in addition, 2 patients experienced pump thrombosis (6.3%). Conclusions: Despite morbidity, use of the HeartMate II LVAD as bridge-to-transplant therapy is associated with excellent survival and low mortality rates. We found a marked decrease in morbidity related to right ventricular failure, to device-related infections, and to thromboembolic events. However, the requirements for anticoagulation therapy may be associated with increased mediastinal and gastrointestinal bleeding. Strategies to optimize anticoagulation therapy may further improve results for these critically ill patients. © 2008 The Society of Thoracic Surgeons.

DOI 10.1016/j.athoracsur.2008.06.030
Citations Scopus - 183
2008 John R, Kamdar F, Liao K, Colvin-Adams M, Miller L, Joyce L, Boyle A, 'Low thromboembolic risk for patients with the Heartmate II left ventricular assist device', Journal of Thoracic and Cardiovascular Surgery, 136 1318-1323 (2008)

Objective: Thromboembolic events can occur in up to 20% of patients with a left ventricular assist device. The aggressive use of anticoagulation with newer continuous-flow devices... [more]

Objective: Thromboembolic events can occur in up to 20% of patients with a left ventricular assist device. The aggressive use of anticoagulation with newer continuous-flow devices has potentially increased the risk of postoperative bleeding. The predecessor of the HeartMate II left ventricular assist device, the HeartMate XVE (Thoratec Corp, Pleasanton, Calif), was associated with an extremely low thromboembolic risk, even without anticoagulation, because of its unique textured surfaces. Even though several areas of the HeartMate II are textured, a protocol was adopted for this new axial flow pump requiring long-term anticoagulation with warfarin. In our study, we investigated whether the HeartMate II left ventricular assist device is associated with a similarly low thromboembolic risk as the HeartMate XVE. Methods: At our institution, 45 patients (mean age, 57.24 ± 14.2 years) underwent implantation of the HeartMate II; 30 underwent bridge-to-transplantation therapy, 7 underwent destination therapy, and 8 underwent left ventricular assist device exchange for a failed XVE left ventricular assist device. Total duration of HeartMate II support was 352.13 patient-months (mean duration, 7.2 ± 5.2 months). All 45 patients were treated postoperatively with warfarin and aspirin. We recorded use of these 2 medications and monthly international normalized ratios. Prospectively, we also monitored patients for any clinical thromboembolic events and for pump thrombus. Results: Of our 45 study patients, 41 had a mean international normalized ratio of less than 2.0; of those 41 patients, 21 had a mean international normalized ratio of less than 1.6. Because of recurrent gastrointestinal bleeding episodes, 7 patients discontinued warfarin for a total duration of 39.1 patient-months. During the entire period of HeartMate II support, we noted 1 thromboembolic event. In addition, another patient had a suspected left ventricular assist device pump thrombus that resolved with a high-intensity heparin anticoagulation protocol (international normalized ratio, 1.3). Conclusions: Our preliminary single-center analysis suggests that the HeartMate II is associated with an extremely low thromboembolic risk and with less stringent requirements for anticoagulation. Selected patients at high risk for bleeding can be safely followed with either no or extremely low anticoagulation requirements for prolonged periods. © 2008 The American Association for Thoracic Surgery.

DOI 10.1016/j.jtcvs.2007.12.077
Citations Scopus - 125
2008 Garcia S, Kandar F, Boyle A, Colvin-Adams M, Lliao K, Joyce L, John R, 'Effects of Pulsatile- and Continuous-flow Left Ventricular Assist Devices on Left Ventricular Unloading', Journal of Heart and Lung Transplantation, 27 261-267 (2008)

Background: In patients with end-stage heart failure, the use of left ventricular assist devices (LVADs) has improved clinical outcomes. Although newer continuous-flow devices hav... [more]

Background: In patients with end-stage heart failure, the use of left ventricular assist devices (LVADs) has improved clinical outcomes. Although newer continuous-flow devices have significant advantages, the effect of continuous flow on left ventricular unloading and hemodynamics is less well established. The aim of this investigation was to compare the effects of pulsatile- vs continuous-flow LVADs on left ventricular reverse remodeling and hemodynamic indices. Methods: Thirty-five patients undergoing implantation with a pulsatile volume displacement pump operating at fixed speed (n = 15; HeartMate XVE; Thoratec Corp., Pleasanton, CA) or a continuous-flow rotary pump with an axial design operating at a fixed rotor speed (n = 20; HeartMate II; Thoratec) were evaluated. Right heart catheterization and echocardiography were performed pre-operatively, and at 1- and 6-month follow-up intervals. Results: Thirty-five of 40 eligible patients with end-stage heart failure were included in this study. When used at fixed speed, use of both devices led to a substantial reduction in left ventricular volumes and dimensions at 1 month (p < 0.01). A marked and sustained reduction in filling pressures was also noted with both devices at 1 and 6 months (p < 0.01). The volume and pressure unloading effects of the HeartMate XVE were not superior to those with the HeartMate II (all p-values not statistically significant). Conclusions: Substantial left ventricular unloading and hemodynamic improvement is achieved with the HeartMate XVE and the HeartMate II. We conclude that continuous-flow LVADs are as effective as pulsatile-flow LVADs with regard to degree of left ventricular unloading and cardiac hemodynamics. © 2008 International Society for Heart and Lung Transplantation.

DOI 10.1016/j.healun.2007.12.001
Citations Scopus - 65
2008 Bart BA, Goldsmith SR, Boyle A, Costanzo MR, 'Renal Function and Ultrafiltration', Journal of Cardiac Failure, 14 533-534 (2008)
DOI 10.1016/j.cardfail.2008.03.005
2008 Dahle TG, Sobotka PA, Boyle AJ, 'A practical guide for ultrafiltration in acute decompensated heart failure', Congestive Heart Failure, 14 83-88 (2008)

Acute decompensated heart failure is the most common reason for inpatient hospital admission. Most patients admitted for decompensated heart failure are by definition diuretic-res... [more]

Acute decompensated heart failure is the most common reason for inpatient hospital admission. Most patients admitted for decompensated heart failure are by definition diuretic-resistant. The therapeutic objective for these patients is volume and sodium removal and restoration of diuretic sensitivity. In a significant proportion of patients, this objective is not met, subjecting patients to readmission for recurrent heart failure decompensation. Ultrafiltration therapy offers the potential of greater volume and sodium removal as compared with conventional therapies in a more expeditious manner. Ultrafiltration can be safely and effectively accomplished in a non-intensive care setting but relies on earlier discharge with reduced readmission rates to be economically feasible. This paper reviews the current data regarding ultrafiltration therapy and provides a practical guide to patient selection, implementation and management of this therapy. ©2008 Le Jacq.

DOI 10.1111/j.1751-7133.2008.07649.x
Citations Scopus - 13
2008 Boyle AJ, Schuleri KH, Lienard J, Vaillant R, Chan MY, Zimmet JM, et al., 'Quantitative Automated Assessment of Myocardial Perfusion at Cardiac Catheterization', AMERICAN JOURNAL OF CARDIOLOGY, 102 980-987 (2008) [C1]
DOI 10.1016/j.amjcard.2008.05.064
Citations Scopus - 8Web of Science - 8
2007 Boyle AJ, Chan MY, Dib J, Kapur NK, Kraft S, Vaillant R, et al., 'Assessment of a novel angiographic image stabilization system for percutaneous coronary intervention', Journal of Interventional Cardiology, 20 153-157 (2007)

Background: Optimization of coronary images for percutaneous coronary intervention (PCI) remains difficult due to cardiac motion throughout the respiratory and cardiac cycles. We ... [more]

Background: Optimization of coronary images for percutaneous coronary intervention (PCI) remains difficult due to cardiac motion throughout the respiratory and cardiac cycles. We tested a novel system to stabilize angiographic images at the region of interest in order to assist during PCI. Methods: Patients undergoing PCI to the right coronary artery (RCA) (group 1, n = 22) or complex PCI (group 2, n = 16) were prospectively enrolled and the angiographic image sequences of patients who died suddenly of confirmed or presumed stent thrombosis following PCI (group 3, n = 16) were retrospectively reviewed. All image sequences were analyzed off-line by three cardiologists before and after image stabilization for accuracy of stent placement, presence of residual edge dissection, and adequacy of procedural outcome. Results: Image stabilization was successful in 100% of cases in a mean time of 95 ± 71 seconds and was considered to be helpful in 13.6% of group 1, in 18.3% of group 2, and in 10% of group 3 cases. There was good correlation between observers with a kappa statistic of 0.85 to 1.0 for all observations. However, there was no difference in the reviewers' opinions of stent placement, presence of edge dissection, or adequacy of procedural result when comparing the standard angiographic views and the stabilized images. In particular, no previously unrecognized edge dissections were apparent in group 3 with stabilized display. Conclusion: Image stabilization centered on the region of interest was considered helpful in a small subset of patients, particularly the complex PCI patients. However, no differences in objective parameters could be demonstrated. © 2007, the Author.

DOI 10.1111/j.1540-8183.2007.00242.x
2007 Burjonroppa SC, Boyle AJ, Yeghiazarians Y, 'Is it time to burst the "balloon" for high-risk patients?', Journal of Invasive Cardiology, 19 347-348 (2007)
2007 Connelly KA, Boyle AJ, Kelly DJ, 'Angiotensin II and the cardiac complications of diabetes mellitus', Current Pharmaceutical Design, 13 2721-2729 (2007)

The prevalence of diabetes has reached epidemic proportions in the developed world and is expect to increase to 5.4% by 2025. This has resulted in an unprecedented number of patie... [more]

The prevalence of diabetes has reached epidemic proportions in the developed world and is expect to increase to 5.4% by 2025. This has resulted in an unprecedented number of patients experiencing the macro- and micro-vascular complications of diabetes, such as renal, retinal, neurological and cardiac dysfunction. Premature coronary artery disease and cardiac failure are vastly over-represented in the diabetic population, with significant morbidity and mortality. In fact, the rate of cardiac events in patients with diabetes is equivalent to non-diabetic patients with a previous myocardial infarction. Epidemiological evidence, combined with the results of large scale trials blocking the renin-angiotensin system (RAS) have provided data to support the hypothesis that angiotensin II and its interaction with the metabolic changes associated with diabetes mellitus is responsible for the pathogenesis of many of these complications. This review focuses on the role of the RAS and the development of diabetic cardiac disease. © 2007 Bentham Science Publishers Ltd.

DOI 10.2174/138161207781662984
Citations Scopus - 17
2007 John R, Liao K, Lietz K, Kamdar F, Colvin-Adams M, Boyle A, et al., 'Experience with the Levitronix CentriMag circulatory support system as a bridge to decision in patients with refractory acute cardiogenic shock and multisystem organ failure', Journal of Thoracic and Cardiovascular Surgery, 134 351-358 (2007)

Objective: Patients with refractory acute cardiogenic shock and multisystem organ failure have a poor outcome with implantation of permanent ventricular assist devices. We review ... [more]

Objective: Patients with refractory acute cardiogenic shock and multisystem organ failure have a poor outcome with implantation of permanent ventricular assist devices. We review our experience with the use of the CentriMag (Levitronix LLC, Waltham, Mass) circulatory support system in such patients whose neurologic status was uncertain. Methods: From January 2004 to June 2006, 30 patients underwent CentriMag circulatory support system placement at the University of Minnesota. Of these patients, 12 were transferred from an outside hospital with refractory acute cardiogenic shock requiring biventricular support; they are the focus of this study. Results: Of our 12 study patients, 8 underwent successful bridging to the HeartMate XVE (Thoratec Corp, Pleasanton, Calif) ventricular assist device after biventricular support (mean support time of 9.4 days, range: 5-22 days). Another 2 patients underwent successful explantation (after 8 and 9 days); the remaining 2 patients died (after 4 days). Thus, the survival on CentriMag support, to either bridge or recovery, was 83% (10/12). Of the 8 patients who subsequently underwent HeartMate implantation, 5 also underwent a heart transplant within 6.9 months (range, 4.5-10 months), another 2 are still awaiting a transplant, and 1 died of sepsis and right ventricular failure 3 days after HeartMate implantation. Thus, for our 12 study patients, long-term survival was 75% at 1 month and 62.5% at 1 year. Conclusions: Our aggressive strategy in this group of patients involved early operative intervention and implantation of biventricular support. By using this strategy, we avoided the urgent placement of expensive long-term ventricular assist devices in hemodynamically unstable patients with multisystem organ failure whose neurologic status was uncertain until end-organ recovery and excellent hemodynamic stability were achieved with the relatively inexpensive short-term CentriMag circulatory support system. The excellent midterm outcomes in this group of patients whose original prognosis was poor justify this therapeutic strategy. © 2007 The American Association for Thoracic Surgery.

DOI 10.1016/j.jtcvs.2007.01.085
Citations Scopus - 129
2007 Whitson BA, D'Cunha J, Knutsen AC, Boyle AJ, Liao KK, 'Levitronix Ventricular Assist Devices as a Bridge to Recovery After Profound Biventricular Heart Failure Associated With Pulmonary Aspergillosis', Journal of Heart and Lung Transplantation, 26 345-349 (2007)

A patient with multisystem organ failure and refractory cardiopulmonary shock stemming from Aspergillus pneumonia was treated with 2 Levitronix ventricular assist devices as a bri... [more]

A patient with multisystem organ failure and refractory cardiopulmonary shock stemming from Aspergillus pneumonia was treated with 2 Levitronix ventricular assist devices as a bridge-to-recovery. After ventricular assist device placement, the patient recovered myocardial function. The ventricular assist devices were removed on post-implant Day 7, and the patient made a full long-term recovery. Ventricular assist devices should be strongly considered, as bridges to recovery, to support patients with acute myocardial dysfunction associated with sepsis while the underlying infection is treated. © 2007 International Society for Heart and Lung Transplantation.

DOI 10.1016/j.healun.2007.01.024
Citations Scopus - 8
2007 Boyle A, Maurer MS, Sobotka PA, 'Myocellular and Interstitial Edema and Circulating Volume Expansion as a Cause of Morbidity and Mortality in Heart Failure', Journal of Cardiac Failure, 13 133-136 (2007)

Background: Total body sodium and volume overload are the hallmarks of the congested state in the heart failure patient and result in a variety of deleterious pathophysiologic out... [more]

Background: Total body sodium and volume overload are the hallmarks of the congested state in the heart failure patient and result in a variety of deleterious pathophysiologic outcomes including ventricular chamber dilation, passive congestion of both encapsulated and nonencapsulated vital organs and myocardial edema and ischemia. Methods and Results: We propose that congestion is itself a disease state irrespective of the underlying cardiac or renal dysfunction and that sodium and volume overload are directly related to poor clinical outcomes in such patients. In this model, the target of decongestion therapy should be normalization of total body sodium and volume in an expeditious manner and with a durable result. Conclusions: Additionally, novel tools to continuously measure the effectiveness and adequacy of decongestion therapy in all compartments are required if improved clinical outcomes are to be attained. © 2007 Elsevier Inc. All rights reserved.

DOI 10.1016/j.cardfail.2006.10.015
Citations Scopus - 26
2007 Schuleri KH, Boyle AJ, Hare JM, 'Mesenchymal stem cells for cardiac regenerative therapy', Handbook of Experimental Pharmacology, 180 195-218 (2007)

Until recently, the concept of treating the injured or failing heart by generating new functional myocardium was considered physiologically impossible. Major scientific strides in... [more]

Until recently, the concept of treating the injured or failing heart by generating new functional myocardium was considered physiologically impossible. Major scientific strides in the past few years have challenged the concept that the heart is a post-mitotic organ, leading to the hypothesis that cardiac regeneration could be therapeutically achieved. Bone marrow-derived adult stem cells were among the first cell populations that were used to test this hypothesis. Animal studies and early clinical experience support the concept that therapeutically delivered mesenchymal stem cells (MSCs) safely improve heart function after an acute myocardial infarction (MI). MSCs produce a variety of cardio-protective signalling molecules, and have the ability to differentiate into both myocyte and vascular lineages. Additionally, MSCs are attractive as a cellular vehicle for gene delivery, cell transplantation or for tissue engineering because they offer several practical advantages. They can be obtained in relatively large numbers through standard clinical procedures, and they are easily expanded in culture. The multi-lineage potential of MSC, in combination with their immunoprivileged status, make MSCs a promising source for cell therapy in cardiac diseases. Here we provide an overview of biological characteristics of MSCs, experimental animal studies and early clinical trials with MSCs. In addition, we discuss the routes of cell delivery, cell tracking experiments and current knowledge of the mechanistic underpinnings of their action. © 2007 Springer-Verlag Berlin Heidelberg.

DOI 10.1007/978-3-540-68976-8-9
Citations Scopus - 73
2006 Kocher AA, Schuster MD, Bonaros N, Lietz K, Xiang G, Martens TP, et al., 'Myocardial homing and neovascularization by human bone marrow angioblasts is regulated by IL-8/Gro CXC chemokines', Journal of Molecular and Cellular Cardiology, 40 455-464 (2006)

In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial p... [more]

In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial precursors. We recently isolated endothelial progenitor cells, or angioblasts, in human adult bone marrow which have selective migratory properties for ischemic tissues, including myocardium, to where they home and induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro-alpha CXC chemokine family is significantly increased after acute ischemia, and that this provides a chemoattractant gradient for bone marrow-derived endothelial progenitors, or angioblasts. This chemokine-mediated homing of bone marrow angioblasts to the ischemic heart regulates their ability to induce myocardial neovascularization, protection against cardiomyocyte apoptosis, and functional cardiac recovery. Together, our results indicate that CXC chemokines play a central role in regulating vasculogenesis in the adult, and suggest that manipulation of interactions between chemokines and their receptors on autologous human bone marrow-derived angioblasts could augment neovascularization of ischemic myocardial tissue. © 2006 Elsevier Ltd. All rights reserved.

DOI 10.1016/j.yjmcc.2005.11.013
Citations Scopus - 120
2006 Wilson AM, Ryan MC, Boyle AJ, 'The novel role of C-reactive protein in cardiovascular disease: Risk marker or pathogen', International Journal of Cardiology, 106 291-297 (2006)

C-reactive protein (CRP) is a non-specific biomarker of inflammation. Recent research has shown that inflammation is an important step in the genesis of atherosclerosis, and is in... [more]

C-reactive protein (CRP) is a non-specific biomarker of inflammation. Recent research has shown that inflammation is an important step in the genesis of atherosclerosis, and is involved in the development of unstable plaques. Measurement of serum levels of CRP using a high sensitivity assay (hsCRP) can demonstrate subclinical inflammatory states, which may reflect vascular inflammation. Clinical studies have shown that elevated hsCRP levels in healthy populations predict vascular events such as myocardial infarction (MI) and stroke as well as the development of diabetes. In patients with acute coronary syndromes, higher hsCRP levels are associated with adverse outcomes and subsequent vascular events. There is data to suggest that aspirin, angiotensin converting enzyme (ACE) inhibitors and HMG Co-A reductase inhibitors (statins), which all reduce vascular event rates, also reduce serum levels of hsCRP and therefore hsCRP levels may potentially guide therapy. As well as having a critical role in risk prediction, recent evidence has emerged implicating CRP directly in atherogenesis. CRP has been found in human atherosclerotic plaque and CRP has been shown to cause endothelial cell dysfunction, oxidant stress and intimal hypertrophy in experimental models. We review the postulated roles of CRP in atherogenesis and prediction of vascular events, as well as discussing current recommendations for CRP testing in patients. © 2005 Elsevier Ireland Ltd. All rights reserved.

DOI 10.1016/j.ijcard.2005.01.068
Citations Scopus - 132
2006 Boyle AJ, Whitbourn R, Schlicht S, Krum H, Kocher A, Nandurkar H, et al., 'Intra-coronary high-dose CD34+ stem cells in patients with chronic ischemic heart disease: A 12-month follow-up', International Journal of Cardiology, 109 21-27 (2006)

Current stem cell protocols for ischemic heart disease are limited by the small numbers of cells that can be obtained by bone marrow aspirate. To increase myocardial delivery of b... [more]

Current stem cell protocols for ischemic heart disease are limited by the small numbers of cells that can be obtained by bone marrow aspirate. To increase myocardial delivery of bone marrow stem cells in patients with chronic ischemic heart disease (CIHD), we used granulocyte colony stimulating factor (G-CSF) for bone marrow mobilization of CD34+ cells, enabling intracoronary infusion of large numbers of CD34+ stem cells. Patients with CIHD (n = 5) demonstrated significantly reduced numbers of CD34+ cells mobilized by G-CSF in comparison to age-matched controls. Sustained reduction in anginal symptoms and improvement in quality of life scores was seen in all patients following infusion of cells. Moreover, mean collateral flow grade at 12-month follow-up angiography significantly improved, indicating sustained myocardial neovascularization. No proliferative retinopathy was induced and no in-stent restenosis seen. However, in two patients with documented increase in collateral flow, complications arose, one developing an acute coronary syndrome and the other a lentigo maligna. These results demonstrate the feasibility of G-CSF mobilization, leukapheresis and intracoronary transfer of CD34+ stem cells in patients with CIHD, but longer-term studies are required to ensure that this protocol is safe and effective. © 2005 Elsevier Ireland Ltd. All rights reserved.

DOI 10.1016/j.ijcard.2005.05.024
Citations Scopus - 83
2006 Amado LC, Schuleri KH, Saliaris AP, Boyle AJ, Helm R, Oskouei B, et al., 'Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy', JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 48 2116-2124 (2006)
DOI 10.1016/j.jacc.2006.06.073
Citations Scopus - 117Web of Science - 106
2006 Dib J, Boyle AJ, Chan M, Resar JR, 'Coronary air embolism: A case report and review of the literature', CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, 68 897-900 (2006)
DOI 10.1002/ccd.20880
Citations Scopus - 16Web of Science - 14
2006 Boyle AJ, Chan M, Dib J, Resar J, 'Catheter-induced coronary artery dissection: Risk factors, prevention and management', Journal of Invasive Cardiology, 18 500-503 (2006)

Guide catheter-induced dissection of the coronary arteries is an uncommon but potentially catastrophic complication of diagnostic and interventional cardiac catheterization. Sever... [more]

Guide catheter-induced dissection of the coronary arteries is an uncommon but potentially catastrophic complication of diagnostic and interventional cardiac catheterization. Several factors placing the individual at higher risk of this complication have been identified. We discuss these risk factors and utilize them to propose methods to prevent dissections. Management options of coronary artery dissection are also discussed.

Citations Scopus - 33
2006 Boyle A, Sobotka PA, 'Redefining the Therapeutic Objective in Decompensated Heart Failure: Hemoconcentration as a Surrogate for Plasma Refill Rate', Journal of Cardiac Failure, 12 247-249 (2006)

Background: Acute decompensated heart failure is a growing epidemiologic problem about which little consensus exists on guidelines and recommendations for therapy. Methods and Res... [more]

Background: Acute decompensated heart failure is a growing epidemiologic problem about which little consensus exists on guidelines and recommendations for therapy. Methods and Results: Available databases suggest that a large percentage of patients are being inadequately decongested while hospitalized, resulting in poor clinical outcomes. This is partly from a lack of an appropriate target to define therapeutic success. The demonstration of a prerenal state by blood work does not indicate adequate decongestion but rather means that the rate of fluid removal has exceeded the plasma refill rate. Hemoconcentration, as evidenced by a rising hematocrit is an appropriate surrogate to indicate that the plasma refill rate has been exceeded by the rate of fluid removal. This surrogate of plasma refill rate can be easily and continuously measured by using an in-line hematocrit sensor during ultrafiltration therapy. Conclusion: We propose that the therapeutic objective in acute decompensated heart failure should be redefined and that the rate of volume extraction should be adjusted to approximate the plasma refill rate and that complete decongestion will have occurred only once hemoconcentration is observed at minimal rates of volume extraction. © 2006 Elsevier Inc. All rights reserved.

DOI 10.1016/j.cardfail.2006.01.011
Citations Scopus - 37
2006 Dahle TG, Blake D, Ali SS, Olinger CC, Bunte MC, Boyle AJ, 'Large Volume Ultrafiltration for Acute Decompensated Heart Failure Using Standard Peripheral Intravenous Catheters', Journal of Cardiac Failure, 12 349-352 (2006)

Background: Ultrafiltration for decompensated heart failure has recently generated significant clinical interest with the development of a portable machine that does not require a... [more]

Background: Ultrafiltration for decompensated heart failure has recently generated significant clinical interest with the development of a portable machine that does not require an intensive care or dialysis unit. This case series was designed to demonstrate the feasibility and effectiveness of performing large volume ultrafiltration via peripherally inserted standard intravenous (IV) catheters in patients with acute decompensated heart failure. Methods and Results: Nine hospitalized patients with decompensated heart failure underwent peripheral ultrafiltration (PUF) therapy with peripheral IV catheters. The mean length of time of PUF therapy was 33.3 ± 20.0 hours with a mean volume removed of 7.0 ± 4.9 L. All patients experienced a statistically significant mean weight loss of 6.2 ± 5.0 kg, P = .01. There was no statistically significant change in renal function. Conclusion: We report the first successful implementation of ultrafiltration via standard peripheral IV catheters to remove a large volume of fluid over an extended period of time reliably in a small group of patients. The ability to use PUF therapy via peripheral IV catheters will potentially allow this therapy to be implemented more easily in a variety of care settings to treat patients with resistant heart failure. © 2006 Elsevier Inc. All rights reserved.

DOI 10.1016/j.cardfail.2006.02.012
Citations Scopus - 31
2006 Boyle AJ, Schulman SP, Hare JM, 'Is stem cell therapy ready for patients? Stem cell therapy for cardiac repair - Ready for the next step', CIRCULATION, 114 339-352 (2006)
DOI 10.1161/CIRCULATIONAHA.105.590653
Citations Scopus - 141Web of Science - 111
2005 Xiang G, Seki T, Schuster MD, Witkowski P, Boyle AJ, See F, et al., 'Catalytic degradation of vitamin D up-regulated protein 1 mRNA enhances cardiomyocyte survival and prevents left ventricular remodeling after myocardial ischemia', Journal of Biological Chemistry, 280 39394-39402 (2005)

Vitamin D3 up-regulated protein 1 (VDUP1) is a key mediator of oxidative stress on various cellular processes via downstream effects on apoptosis signaling kinase 1 (ASK1) and p38... [more]

Vitamin D3 up-regulated protein 1 (VDUP1) is a key mediator of oxidative stress on various cellular processes via downstream effects on apoptosis signaling kinase 1 (ASK1) and p38 mitogen-activated protein kinase (MAPK). Here, we report that VDUP1 expression is significantly increased in rat hearts following acute myocardial ischemia, suggesting it may have important regulatory effects on cardiac physiological processes during periods of oxidative stress. Transfection of H9C2 cardiomyoblasts with a sequence-specific VDUP1 DNA enzyme to down-regulate VDUP1 mRNA expression significantly reduced apoptosis and enhanced cell survival under conditions of H 2 O 2 stress, and these effects involved inhibition of ASK1 activity. Direct intracardiac injection of the DNA enzyme at the time of acute myocardial infarction reduced myocardial VDUP1 mRNA expression and resulted in prolonged reduction in cardiomyocyte apoptosis and ASK1 activity. Moreover, down-regulation of VDUP1 was accompanied by significant reduction in cardiac expression of pro-collagen type I a2 mRNA level, as well as marked reduction in myocardial scar formation. These features were accompanied by significant improvement in cardiac function. Together, these results suggest a direct role for VDUP1 in the adverse effects of ischemia and oxidative stress on cardiomyocyte survival, left ventricular collagen deposition, and cardiac function. Strategies to inhibit VDUP1 expression and/or function during acute ischemic events may be beneficial to cardiac functional recovery and prevention of left ventricular remodeling. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI 10.1074/jbc.M502966200
Citations Scopus - 53
2005 Boyle AJ, Kelly DJ, Zhang Y, Cox AJ, Gow RM, Way K, et al., 'Inhibition of protein kinase C reduces left ventricular fibrosis and dysfunction following myocardial infarction', Journal of Molecular and Cellular Cardiology, 39 213-221 (2005)

Despite current therapies, chronic heart failure (CHF) remains a major complication of myocardial infarction (MI). The pathological changes that follow MI extend to regions remote... [more]

Despite current therapies, chronic heart failure (CHF) remains a major complication of myocardial infarction (MI). The pathological changes that follow MI extend to regions remote from the site of infarction (non-infarct zone, NIZ) where fibrosis is a prominent finding. Although the mechanisms underling this adverse remodeling are incompletely understood, activation of protein kinase C has recently been implicated in its pathogenesis. MI was induced in Sprague-Dawley rats by ligation of the left anterior descending coronary artery. One week post-MI, animals were randomized to receive the PKC-inhibitor, ruboxistaurin (LY333531) for 4 weeks, or no treatment. When compared with sham-operated animals, post-MI rats showed a 33 ± 7% reduction in fractional shortening over a 4 weeks period, that was attenuated by treatment with ruboxistaurin (6 ± 11%, P < 0.05). Increased matrix deposition was noted in the NIZ, particularly in the subendocardial region of post-MI rats, in association with elevated expression of the profibrotic growth factor, transforming growth factor-beta. These findings were also significantly reduced by ruboxistaurin. PKC-inhibition with ruboxistaurin led to attenuation in both the pathological fibrosis and impaired cardiac function that follow experimental MI, suggesting a possible role for this agent in preventing post-infarction heart failure. © 2005 Elsevier Ltd. All rights reserved.

DOI 10.1016/j.yjmcc.2005.03.008
Citations Scopus - 53
2005 Boyle AJ, Schuster M, Witkowski P, Xiang G, Seki T, Way K, Itescu S, 'Additive effects of endothelial progenitor cells combined with ACE inhibition and ß-blockade on left ventricular function following acute myocardial infarction', JRAAS - Journal of the Renin-Angiotensin-Aldosterone System, 6 33-37 (2005)

Animal studies have demonstrated the efficacy of endothelial progenitor cells (EPCs) in preventing left ventricular (LV) remodelling following myocardial infarction (MI). Prelimin... [more]

Animal studies have demonstrated the efficacy of endothelial progenitor cells (EPCs) in preventing left ventricular (LV) remodelling following myocardial infarction (MI). Preliminary human studies are underway, yet no studies have demonstrated efficacy in combination with standard medical therapy, i.e. angiotensin-converting enzyme (ACE) inhibitors and ß-blockers. Nude rats underwent left anterior descending coronary artery ligation to induce MI. Animals were randomised to receive no treatment MI, n=5), quinapril 200 mg/L + metoprolol 2 g/L (ACE/BB, n=5), two million EPCs intravenously (EPC, n=5)or both (ACE/BB + EPC [n=51), then sacrificed after two weeks treatment. ACE/BB resulted in a 75% reduction in fibrosis in the region remote from the MI (p < 0.05), but EPC therapy had little effect here. Conversely, EPC therapy induced neovascularisation at the peri-infarct rim, thereby preventing peri-infarct apoptosis by 81% (p < 0.05). Acting via different but complementary mechanisms, the combination of ACE/BB + EPCs resulted in a greater overall improvement in LV function on echocardiography than either therapy alone. Clinical triaJs using stem cell therapy in conjunction with standard medical treatment are warranted.

Citations Scopus - 18
2005 Bart BA, Boyle A, Bank AJ, Anand I, Olivari MT, Kraemer M, et al., 'Ultrafiltration versus usual care for hospitalized patients with heart failure: The relief for acutely fluid-overloaded patients with decompensated congestive heart failure (RAPID-CHF) trial', Journal of the American College of Cardiology, 46 2043-2046 (2005)

OBJECTIVES: The purpose of this research was to assess the safety and efficacy of ultrafiltration (UF) in patients admitted with decompensated congestive heart failure (CHF). BACK... [more]

OBJECTIVES: The purpose of this research was to assess the safety and efficacy of ultrafiltration (UF) in patients admitted with decompensated congestive heart failure (CHF). BACKGROUND: Ultrafiltration for CHF is usually reserved for patients with renal failure or those unresponsive to pharmacologic management. We performed a randomized trial of UF versus usual medical care using a simple UF device that does not require special monitoring or central intravenous access. METHODS: Patients admitted for CHF with evidence of volume overload were randomized to a single, 8 h UF session in addition to usual care or usual care alone. The primary end point was weight loss 24 h after the time of enrollment. RESULTS: Forty patients were enrolled (20 UF, 20 usual care). Ultrafiltration was successful in 18 of the 20 patients in the UF group. Fluid removal after 24 h was 4,650 ml and 2,838 ml in the UF and usual care groups, respectively (p = 0.001). Weight loss after 24 h, the primary end point, was 2.5 kg and 1.86 kg in the UF and usual care groups, respectively (p = 0.240). Patients tolerated UF well. CONCLUSIONS: The early application of UF for patients with CHF was feasible, well-tolerated, and resulted in significant weight loss and fluid removal. A larger trial is underway to determine the relative efficacy of UF versus standard care in acute decompensated heart failure. © 2005 by the American College of Cardiology Foundation.

DOI 10.1016/j.jacc.2005.05.098
Citations Scopus - 252
2005 Boyle A, 'Ultrafiltration for acute decompensated heart failure', Expert Review of Medical Devices, 2 689-697 (2005)

For the 13th consecutive year, acute decompensated heart failure is the most common reason for admission to American hospitals. Most patients admitted for decompensated heart fail... [more]

For the 13th consecutive year, acute decompensated heart failure is the most common reason for admission to American hospitals. Most patients admitted for decompensated heart failure are by definition, diuretic resistant. The therapeutic objective in these patients is volume and sodium removal, and the restoration of diuretic sensitivity. In a significant proportion of patients, this objective is not met, subjecting patients to readmission for recurrent (or continued) heart failure decomponsation. Ultrafiltration therapy offers the potential of greater volume and sodium removal as compared with conventional therapies in a more expeditious manner. Ultrafiltration can be accomplished safely, quickly and on a regular telemetry ward in extremely ill patients, but relies on earlier discharge with reduced readmission rates to be economically feasible. © 2005 Future Drugs Ltd.

DOI 10.1586/17434440.2.6.689
Citations Scopus - 6
2004 Xiang G, Seki T, Schuster M, Witkowski P, Boyle AJ, See F, et al., 'Down-regulation of Plasminogen Activator Inhibitor 1 Expression Promotes Myocardial Neovascularization by Bone Marrow Progenitors', J Biol Chem, 1657-1666 (2004)
DOI 10.1084/jem.20040221
Citations Scopus - 32
2004 La Gerche A, Boyle A, Wilson AM, Prior DL, 'No Evidence of Sustained Myocardial Injury Following an Ironman Distance Triathlon', International Journal of Sports Medicine, 25 45-49 (2004)

We aimed to determine whether an Ironman distance triathlon resulted in sustained myocardial injury detected by electrocardiography, biochemical markers or echocardiographic asses... [more]

We aimed to determine whether an Ironman distance triathlon resulted in sustained myocardial injury detected by electrocardiography, biochemical markers or echocardiographic assessment of left ventricular systolic and diastolic function. Electrocardiograms, blood for analysis of creatine kinase (CK) and its MB fraction, cardiac troponin I (cTn1) and echocardiograms were obtained in 15 male athletes prior to and at a mean of 4.7 days after competing in the Australian Ironman Triathlon. Regional wall motion scores, left ventricular ejection fraction (LVEF) and mitral inflow parameters were determined from the echocardiograms by a blinded investigator. Levels of cTn1 were undetectable in all athletes and total CK was mildly elevated in 7/15 athletes prior to the event. Baseline wall motion, ejection fraction and diastolic filling were normal in all athletes. CK levels were increased post-race (p < 0.05) with a mean post-race level of 451U/l. Levels of cTn1 were undetectable post-race in 14 athletes with a level of 0.9 µg/l recorded in one athlete, although all were within the laboratory's normal range for the assay. Mitral inflow parameters and LVEF did not change post-race and regional wall motion was normal in 14 of 15 athletes. Regional wall motion abnormalities detected in 1 athlete had resolved by 25 days post-race. These findings indicate that ultraendurance exercise does not result in sustained myocardial injury in this group of elite athletes.

DOI 10.1055/s-2003-45236
Citations Scopus - 26
2004 Boyle A, Colvin-Adams M, 'Recipient selection and management', Seminars in Thoracic and Cardiovascular Surgery, 16 358-363 (2004)

Cardiac transplantation remains the definitive surgical solution for Stage D heart failure. However, the lack of availability of donor organs makes patient selection crucial to ap... [more]

Cardiac transplantation remains the definitive surgical solution for Stage D heart failure. However, the lack of availability of donor organs makes patient selection crucial to appropriate resource utilization. All feasible medical and surgical alternatives should be explored before consideration of transplantation is undertaken. A cardiac transplantation evaluation should be thorough to exclude patients with preexisting serious comorbidities, with particular attention being paid to renal dysfunction, pulmonary hypertension, and panel reactive antibody levels. Once accepted for listing as a cardiac transplantation recipient, patients are assigned a priority status based on the severity of illness. Organs are allocated on the basis on status level, blood type, body size, and length of time at a given status level. © 2004 Elsevier Inc. All rights reserved.

DOI 10.1053/j.semtcvs.2004.09.007
Citations Scopus - 15
2004 Wilson AM, Boyle AJ, Fox P, 'Management of ischaemic heart disease in women of child-bearing age', Internal Medicine Journal, 34 694-697 (2004)

Ischaemic heart disease is rare in young women but is expected to increase with increasing average age of child bearing. Diagnosis of myocardial ischaemia in this group is complic... [more]

Ischaemic heart disease is rare in young women but is expected to increase with increasing average age of child bearing. Diagnosis of myocardial ischaemia in this group is complicated by limited data about maternal and fetal safety of the standard diagnostic tests routinely used in other patients. Management of these patients remains difficult, as many standard treatments, such as beta- blockers and angiotensin converting enzyme inhibitors are pregnancy category C or D, and there is little experience with many of the newer treatments such as coronary artery stenting, clopidogrel and glycoprotein IIb/IIIa inhibitors in pregnancy. An interesting case of a woman, who had an acute myocardial infarction treated with thrombolysis and coronary artery stenting, and who subsequently became pregnant, is reported here, and other published reports regarding the management of coronary artery disease, both acute and chronic, in pregnant women are explored.

Citations Scopus - 18
2003 Connelly KA, Boyle A, Wilson A, MacIsaac A, Fox P, Whitbourn R, 'Coronary artery stent thrombosis associated with exercise testing', Heart Lung and Circulation, 12 66-69 (2003)

Chest pain following coronary artery stenting is common, yet finding the cause can be difficult. Exercise testing has long been used in the assessment of chest pain, but its usefu... [more]

Chest pain following coronary artery stenting is common, yet finding the cause can be difficult. Exercise testing has long been used in the assessment of chest pain, but its usefulness in patients who have recently undergone coronary artery stenting is in doubt. A case of exercise testing appearing to precipitate acute stent thrombosis in a patient several weeks post-coronary artery stenting is reported and compared to a similar case in the literature. The role of exercise testing in the assessment of chest pain early after coronary artery stenting is then reviewed.

DOI 10.1046/j.1444-2892.2003.00165.x
Citations Scopus - 3
2002 Boyle AJ, Wilson AM, Connelly K, McGuigan L, Wilson J, Whitbourn R, 'Improvement in timing and effectiveness of external cardiac compressions with a new non-invasive device: The CPR-Ezy', Resuscitation, 54 63-67 (2002)

Prompt and effective cardiopulmonary resuscitation (CPR) is the first link in the chain of survival following cardiac arrest. We assessed a new device, the CPR-Ezy¿ (Medteq Innov... [more]

Prompt and effective cardiopulmonary resuscitation (CPR) is the first link in the chain of survival following cardiac arrest. We assessed a new device, the CPR-Ezy¿ (Medteq Innovations Pty Ltd., Brisbane, Australia), to aid timing and effectiveness of external cardiac compressions (ECC), by 32 subjects who had prior community-based training in CPR. ECC was performed on a manikin for 4 min by all subjects without and with the device. There was a statistically significant improvement in timing of ECC. Effectiveness of compressions was also improved over the whole time period, especially so in the last minute. We conclude that the CPR-Ezy can improve timing and effectiveness of ECC, and reduce the effects of resuscitator fatigue, in community-trained subjects. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI 10.1016/S0300-9572(02)00049-7
Citations Scopus - 53
2001 Boyle AJ, Jelinek MV, 'Rethinking the approach to abdominal aortic aneurysms [7]', Lancet, 357 2140 (2001)
Citations Scopus - 1
2001 Boyle AJ, Wilson AM, Maclsaac AI, Daffy J, Stanley P, 'Mural endocarditis caused by Salmonella virchow: Survival with conservative treatment', Heart Lung and Circulation, 10 161-163 (2001)

We describe a case of endocarditis caused by Salmonella enterica serotype virchow, which was treated conservatively with antibiotics alone. It is the only reported case of surviva... [more]

We describe a case of endocarditis caused by Salmonella enterica serotype virchow, which was treated conservatively with antibiotics alone. It is the only reported case of survival from salmonella endocarditis with conservative treatment, and the first reported case of endocarditis caused by Salmonella virchow. The changing prevalence, virulence patterns and importance of salmonella species in endocarditis are discussed.

DOI 10.1046/j.1444-2892.2001.00099.x
Citations Scopus - 1
Show 114 more journal articles

Conference (13 outputs)

Year Citation Altmetrics Link
2017 Murtha LA, Mabotuwana NR, Hardy SA, Boyle AJ, 'Fibulin-3 as a Potential Therapeutic Target for Cardiac Fibrosis', JOURNAL OF CARDIAC FAILURE, Dallas, TX (2017)
Co-authors Lucy Murtha
2016 Davies AJ, Boyle A, 'Trends in characteristics and outcomes of elderly patients presenting with acute myocardial infarction', EUROPEAN HEART JOURNAL, Rome, ITALY (2016)
2016 Davies AJ, Boyle A, 'Differences in age and outcomes of aboriginal and non-aboriginal Australians presenting with acute myocardial infarction', EUROPEAN HEART JOURNAL, Rome, ITALY (2016)
2016 Khan AA, Williams T, Savage L, Stewart P, Fletcher P, Boyle A, 'PRE-HOSPITAL THROMBOLYSIS VERSUS PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION IN REGIONAL AUSTRALIA: REAL WORLD LONG TERM FOLLOW UP', JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Chicago, IL (2016)
2014 Esposito M, Shah NN, Korabathina R, Pan C, Paruchuri V, Finley J, et al., 'Quantitative Assessment of Myocardial Perfusion Using Time-Density Curve Analysis After Elective Percutaneous Coronary Intervention', JOURNAL OF INVASIVE CARDIOLOGY (2014) [E3]
Citations Web of Science - 1
2011 Watanabe M, See F, Kompa AR, Boyle AJ, Gilbert RE, Connelly K, et al., 'Delayed Tranilast Treatment Reduces Pathological Fibrosis Following Myocardial Infarction And In Uremic Cardiomyopathy', CIRCULATION (2011) [C3]
2008 Schuleri KH, Amado LC, Boyle AJ, Centola M, Saliaris AP, Gutman MR, et al., 'Early improvement in cardiac tissue perfusion due to mesenchymal stem cells', AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Amelia Isl, FL (2008) [E1]
DOI 10.1152/ajpheart.00762.2007
Citations Web of Science - 101
2007 Schuleri KH, Centola M, Zimmet JM, Boyle AJ, Feigenbaum GS, Heldman AW, et al., 'Intramyocardial allogeneic mesenchymal stem cells reduce infarct size in a porcine model of chronic ischemic cardiomyopathy', JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, New Orleans, LA (2007)
2007 Schuleri KH, Amado LC, Boyle AJ, Centola M, Zimmet JM, Saliaris AP, et al., 'Early improvement in cardiac tissue perfusion due to mesenchymal stem cells', EUROPEAN HEART JOURNAL (2007) [E3]
2006 Amado LC, Schuleri KH, Saliaris AP, Helm R, Boyle A, Oskouei B, et al., 'Impact of mesenchymal stem cell therapy on scar composition and cardiac regional function', JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Atlanta, GA (2006)
2006 Schuleri KH, Boyle A, Amado LC, Saliaris AP, Oskouei BN, Young RG, et al., 'Allogeneic mesenchymal stem cells improve vessel maturation and reduce apoptosis in regions of ischemically damaged myocardium', JOURNAL OF CARDIAC FAILURE, Seattle, WA (2006)
DOI 10.1016/j.cardfail.2006.06.037
2006 Mazhari R, Schuleri KH, Zimmet JM, Saliaris AP, Amado LC, Boyle AJ, et al., 'Cell tracking following the intramyocardial injection of mesenchymal cells after myocardial infarction', JOURNAL OF CARDIAC FAILURE, Seattle, WA (2006)
DOI 10.1016/j.cardfail.2006.06.067
2006 Mazhari R, Schuleri KH, Zimmet JM, Boyle AJ, Heldman AW, Hare JM, 'Cell tracking following the intramyocardial injection of MSCs after myocardial infarction', CIRCULATION, Chicago, IL (2006)
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Grants and Funding

Summary

Number of grants 16
Total funding $2,310,926

Click on a grant title below to expand the full details for that specific grant.


20175 grants / $330,046

HNE Translational research Fellowship for Dr Arshad Khan$137,538

Funding body: Hunter New England Health LHD, NSW Health

Funding body Hunter New England Health LHD, NSW Health
Project Team

Arshad Khan, Andrew Boyle

Scheme Translational Research Fellowship
Role Investigator
Funding Start 2017
Funding Finish 2018
GNo
Type Of Funding Other Public Sector - State
Category 2OPS
UON N

A randomised clinical trial of STAtin therapy for Reducing Events in the Elderly (STAREE)$95,174

Funding body: Monash University

Funding body Monash University
Project Team Professor Andrew Boyle, Prof Sophia Zoungas
Scheme Research Grant
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1601140
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

Characterising the role of Fibulin-3 in health and disease$67,500

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Lucy Murtha, Professor Andrew Boyle
Scheme Project Grant
Role Investigator
Funding Start 2017
Funding Finish 2018
GNo G1700327
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

Injectable Polymer for Cardiac Regeneration – a Pilot Study$20,000

Funding body: John Hunter Hospital Charitable Trust

Funding body John Hunter Hospital Charitable Trust
Project Team Professor Andrew Boyle, Professor Randall Lee
Scheme Research Grant
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1700571
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

Feasibility and engagement strategies for a cardiovascular disease prevention program targeting a high need, low health literacy rural community.$9,834

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Tracy Schumacher, Doctor Leanne Brown, Professor Jennifer May, Professor Clare Collins, Professor Andrew Boyle
Scheme Linkage Pilot Research Grant
Role Investigator
Funding Start 2017
Funding Finish 2017
GNo G1701268
Type Of Funding Internal
Category INTE
UON Y

20163 grants / $303,400

Fibulin-3 and Cardiac Fibrosis$266,655

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Andrew Boyle
Scheme Project Grant
Role Lead
Funding Start 2016
Funding Finish 2018
GNo G1600019
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

Profiling Human Cardiac Stem Cells$21,745

Funding body: John Hunter Hospital Charitable Trust

Funding body John Hunter Hospital Charitable Trust
Project Team Professor Andrew Boyle, Professor Jennifer Martin
Scheme Research Grant
Role Lead
Funding Start 2016
Funding Finish 2016
GNo G1600704
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

Knockout model for heart fibrosis$15,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Andrew Boyle
Scheme Project Grant
Role Lead
Funding Start 2016
Funding Finish 2016
GNo G1600595
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

20152 grants / $45,222

MERINO2 - A randomised controlled trial comparing two different antibiotics for blood stream infections caused by the 'ESCaPM' group of antibiotic resistant Gram negative bacteria$25,222

Funding body: John Hunter Hospital Charitable Trust

Funding body John Hunter Hospital Charitable Trust
Project Team Conjoint Professor Josh Davis, Professor Andrew Boyle, Patrick Harris, David Paterson
Scheme Research Grant
Role Investigator
Funding Start 2015
Funding Finish 2015
GNo G1500781
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

Development of a novel model of cardiac scar tissue$20,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Andrew Boyle
Scheme Project Grant
Role Lead
Funding Start 2015
Funding Finish 2015
GNo G1500378
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

20142 grants / $308,258

Fibulin-3 and Cardiac Fibrosis$302,238

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Professor Andrew Boyle
Scheme Project Grant
Role Lead
Funding Start 2014
Funding Finish 2017
GNo G1400574
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

2014 International Visitor from University of California (San Francisco), USA$6,020

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Andrew Boyle, Professor Randall Lee
Scheme International Research Visiting Fellowship
Role Lead
Funding Start 2014
Funding Finish 2014
GNo G1400864
Type Of Funding Internal
Category INTE
UON Y

20121 grants / $33,000

A New Model of Diastolic Heart Failure$33,000

Funding Body: UCSF CTSI Funding Scheme: SOS Grant - Individual Investigator Description: – (Boyle PI) 7/2012 – 6/2013 $30,000

Funding body: Society for Cardiovascular Angiography and Interventions

Funding body Society for Cardiovascular Angiography and Interventions
Project Team

Andrew Boyle

Scheme Fellows Award
Role Lead
Funding Start 2012
Funding Finish 2013
GNo
Type Of Funding Not Known
Category UNKN
UON N

20082 grants / $1,200,000

The Effects of Aging on Left Ventricular Remodeling Following Myocardial Infarction$700,000

Funding Body: NIH National Institutes of Health Funding Scheme: K08 Description: Aging has detrimental effects of outcomes following heart attacks. We study the cellular and molecular mechanisms that lead to these worse outcomes.

Funding body: NIH National Institutes of Health

Funding body NIH National Institutes of Health
Project Team

Andrew Boyle

Scheme K08
Role Lead
Funding Start 2008
Funding Finish 2013
GNo
Type Of Funding Not Known
Category UNKN
UON N

The Influence of Aging on Pressure Overload Cardiomyopathy$500,000

Research Grant Description: The cellular and molecular aspects of left ventricular remodeling in response to pressure overload were studied, with emphasis on age-related changes.

Funding body: Ellison Medical Foundation

Funding body Ellison Medical Foundation
Project Team

Andrew Boyle

Scheme Research Grant
Role Lead
Funding Start 2008
Funding Finish 2012
GNo
Type Of Funding Not Known
Category UNKN
UON N

20031 grants / $91,000

Novel Therapies for the Prevention and Treatment of Left ventricular Remodelling Following Myocardial Infarction.$91,000

Study of new treatments including bone marrow derived stem cells for treatment of post-infarction heart failure

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team

Andrew Boyle

Scheme Scholarships - Medical and Dental Postgraduate Research
Role Lead
Funding Start 2003
Funding Finish 2005
GNo
Type Of Funding Not Known
Category UNKN
UON N
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Research Supervision

Number of supervisions

Completed0
Current7

Total current UON EFTSL

Masters1.5
PhD1.55

Current Supervision

Commenced Level of Study Research Title Program Supervisor Type
2017 PhD The Identification of Novel Proteins Expressed by Human Cardiac Stem and Progenitor Cells to Develop Regenerative Non-Cellular Therapies for Heart Failure PhD (Medicine), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2017 Masters The Impact of Reduction in Left Ventricular End Diastolic Pressure in Patients with ST-segment Elevation Myocardial Infarction. M Philosophy (Medicine), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2017 PhD A nursing led examination of health outcomes in a cardiac catheterisation Laboratory: An examination of contemporary complications PhD (Nursing), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2017 PhD Establishment and Application of an In Vitro 3D Model of the Human Heart to Facilitate Discovery of New Therapies for Myocardial Infarction PhD (Medicine), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2017 PhD Extracellular Matrix Protein 1 (ECM1) in the Ageing and Diseased Mammalian Heart PhD (Medicine), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2016 Masters Heart Failure Outcomes in Hunter New England Area M Philosophy (Medicine), Faculty of Health and Medicine, The University of Newcastle Principal Supervisor
2016 Masters Investigation of Vitamin D¿s Significance to Severe Cardiovascular Disease M Philosophy (Nursing), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
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Research Opportunities

Regeneration of cardiac tissue

PhD scholarship

PHD

Health

1/02/2017 - 30/04/2020

Contact

Ms Stacey Wilks
University of Newcastle
School of Medicine and Public Health
stacey.wilks@newcastle.edu.au

Investigating cardiac fibrosis

Honours

Honours

Hunter Medical Research Institute - Public Health

1/01/2018 - 31/12/2018

Contact

Ms Stacey Wilks
University of Newcastle
School of Medicine and Public Health
stacey.wilks@newcastle.edu.au

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News

PHD Scholarship: Cardiovascular research

September 25, 2017

The Priority Clinical Centre for Cardiovascular Health currently has an opportunity for a new PhD student to receive a fully funded scholarship to research cardiovascular health, under the supervision of Dr Lucy Murtha and Professor Andrew Boyle.

PhD Opportunity: Extracellular matrix protein in pressure overload-induced cardiac fibrosis

July 3, 2017

The Priority Clinical Centre for Cardiovascular Health is seeking expressions of interest for a motivated student to investigate the role of a novel extracellular matrix protein in pressure overload-induced cardiac fibrosis, under the supervision of Professor Andrew Boyle and Dr Lucy Murtha.

Masters Opportunity: Investigating a novel injectable polymer for cardiac regeneration

June 29, 2017

The Priority Clinical Centre for Cardiovascular Health is seeking expressions of interest for a highly motivated student to conduct a Research Masters project investigating novel injectable polymer for cardiac regeneration under the supervision of Professor Andrew Boyle and Dr Lucy Murtha.

Professor Andrew Boyle

Drug trial to reduce scarring after heart scare

December 1, 2015

Hunter heart attack survivors will be among the first in the world to trial a new drug designed to reduce the tissue scarring commonly associated with heart weakening and potential failure.

Professor Andrew Boyle

Position

Professor of Cardiovascular Medicine & Head of Discipline
School of Medicine and Public Health
Faculty of Health and Medicine

Contact Details

Email andrew.boyle@newcastle.edu.au
Phone (02) 4921 4205
Fax (02) 4921 4210

Office

Location HMRI

,
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