ORCID Profile
0000-0002-5442-6985
Current Organisations
Royal Australasian College of Physicians
,
Monash University
,
University of Melbourne
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Publisher: Elsevier BV
Date: 10-2018
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.JACC.2010.07.049
Abstract: The purpose of this study was to test the safety and efficacy of direct injection of cardiosphere-derived cells (CDCs) and their 3-dimensional precursors, cardiospheres, for cellular cardiomyoplasty in a mini-pig model of heart failure after myocardial infarction. Intracoronary administration of CDCs has been demonstrated to reduce infarct size and improve hemodynamic indexes in the mini-pig model, but intramyocardial injection of CDCs or cardiospheres has not been assessed in large animals. Autologous cardiospheres or CDCs grown from endomyocardial biopsies were injected through thoracotomy 4 weeks after anteroseptal myocardial infarction. Engraftment optimization with luciferase-labeled CDCs guided the choice of cell dose (0.5 million cells/site) and target tissue (20 peri-infarct sites). Pigs were randomly allocated to placebo (n = 11), cardiospheres (n = 8), or CDCs (n = 10). Functional data were acquired before injection and again 8 weeks later, after which organs were harvested for histopathology. Beyond the immediate perioperative period, all animals survived to protocol completion. Ejection fraction was equivalent at baseline, but at 8 weeks was higher than placebo in both of the cell-treated groups (placebo vs. CDC, p = 0.01 placebo vs. cardiospheres, p = 0.01). Echocardiographic and hemodynamic indexes of efficacy improved disproportionately with cardiospheres likewise, adverse remodeling was more attenuated with cardiospheres than with CDCs. Provocative electrophysiologic testing showed no differences among groups, and no tumors were found. Dosage-optimized direct injection of cardiospheres or CDCs is safe and effective in preserving ventricular function in porcine ischemic cardiomyopathy. Although CDCs and cardiospheres have equivalent effects on left ventricular ejection fraction, cardiospheres are superior in improving hemodynamics and regional function, and in attenuating ventricular remodeling.
Publisher: American Medical Association (AMA)
Date: 10-2015
Publisher: Elsevier BV
Date: 03-2010
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.IJCARD.2007.07.066
Abstract: Apical ballooning syndrome (ABS) describes acute regional myocardial dysfunction and has a strong association with emotional stress and female sex. Whilst catecholamine excess has been described in this condition, the precise etiology remains elusive. We report the atypical case of a 61 year old male who developed ABS in the absence of a clear precipitant. His concurrent treatment with a vascular endothelial growth factor (VEGF) receptor antagonist may provide an insight into the pathogenesis of this enigmatic condition. We present a biologically plausible explanation as to why VEGF antagonism may have an important role through its modulation of nitric oxide and catecholamine effects. This hypothesis may also provide an important insight into the cardiovascular toxicities associated with this class of drug. In addition, we report the success of treatment with a beta blocker in ABS complicated by a severe left ventricular outflow tract obstruction.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.ATHEROSCLEROSIS.2009.02.025
Abstract: Inflammation and structural factors such as a thin fibrous cap, positive remodeling and large lipid pool have been established as factors associated with coronary plaque instability. This study aimed to investigate the hypothesis that the differential in coronary artery compliance between stenotic and adjacent arterial segments is another factor associated with unstable coronary disease. Forty-one patients undergoing a percutaneous coronary intervention were classified as unstable coronary syndrome (n=19) or stable angina (n=22). Intravascular ultrasound was used to assess external elastic lamina (EEL) cross-sectional area at diastole and systole. Aortic pressure was determined from the coronary guiding catheter. Coronary cross-sectional compliance (C) was calculated as the quotient of systolic-to-diastolic area differential and pulse pressure. C was measured within the stenosis and the adjacent reference segments. EEL cross-sectional area was greater in systole than in diastole in the reference segments, but did not differ within the lesion site. C was greater in the distal reference than the stenotic segments (7.7+/-13.1 vs. 0.0+/-12.3mm(2)mmHg(-1)x10(3), p=0.003). When dichotomized by clinical presentation, the distal-to-stenosis compliance difference was only significant in the unstable coronary syndrome group (stable: distal 4.1+/-13.3 vs. stenosis -0.3+/-13.2mm(2)mmHg(-1)x10(3), ANOVA p=0.48 unstable: distal 11.9+/-11.9 vs. stenosis 0.1+/-11.6mm(2)mmHg(-1)x10(3), ANOVA p=0.006, distal-to-stenosis difference p=0.001). A difference between stenotic and distal reference segment coronary compliance was evident in unstable, but not stable coronary artery disease patients. Coronary compliance differential would increase cyclical forces in the plaque shoulder region, which may contribute to plaque disruption.
Publisher: Oxford University Press (OUP)
Date: 09-06-2011
Abstract: Cardiosphere-derived cells (CDCs) are in clinical development as a regenerative cell product which can be expanded ex vivo from patient cardiac biopsies. Cardiosphere-derived cells are clonogenic, exhibit multilineage differentiation, and exert functional benefits in preclinical models of heart failure. The origin of CDCs remains unclear: are these cells endogenous to the heart, or do they arise from cells that populate the heart via blood-borne seeding? Right ventricular endomyocardial biopsies were obtained from cardiac transplant recipients (n = 10, age 57 ± 15 years), and CDCs expanded from each biopsy. Donor-recipient mismatches were used to probe the origin of CDCs in three complementary ways. First, DNA analysis of short-tandem nucleotide repeats (STRs) was performed on genomic DNA from donor and recipient, then compared with the STR pattern of CDCs. Second, in two cases where the donor was male and the recipient female, CDCs were examined for the presence of X and Y chromosomes by fluorescence in situ hybridization. Finally, in two cases, quantitative PCR (qPCR) was performed for in idual-specific polymorphisms of a major histocompatability locus to quantify the contribution of recipient cells to CDCs. In no case was recipient DNA detectable in the CDCs by STR analysis. In the two cases in which a female patient had received a male heart, all CDCs examined had an X and Y chromosome, similarly indicating exclusively donor origin. Likewise, qPCR on CDCs did not detect any recipient DNA. Cardiosphere-derived cells are of endogenous cardiac origin, with no detectable contribution from extra-cardiac seeding.
Publisher: BMJ
Date: 28-06-2018
DOI: 10.1136/HEARTJNL-2017-312779
Abstract: A 42-year-old woman presented with anterior ST elevation myocardial infarction. Urgent coronary angiography revealed tapering then occlusion of the distal left anterior descending (LAD) coronary artery with no flow in the distal LAD (figure 1A). Balloon angioplasty with a 2.0×8 mm balloon re-established flow into the distal LAD. An angiogram of the right external iliac artery was also performed (figure 1B). Figure 1 Invasive angiography of the left coronary system (A) and the right external iliac artery (B). The coronary angiogram (A) shows tapering and then occlusion (arrow) of the distal left anterior descending coronary artery. Which of the following explains the abnormal appearance of the external iliac artery (figure 1B)? Atherosclerosis. Concertina effect. Fibromuscular dysplasia. Perforation. Multiple aneurysms.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2006
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.AMJCARD.2010.06.010
Abstract: A meta-analysis of published studies was conducted to evaluate the incidence, predictors, and clinical outcomes of stent fractures. Eight studies with 108 stent fractures in 5,321 patients were analyzed using the Bayesian method. Study end points included in-stent restenosis (ISR) and target lesion revascularization (TLR). The mean incidence of stent fracture per patient was 4.0% (95% confidence interval 0.4% to 16.3%). All cases, except 1, were reported with sirolimus-eluting stents. The incidence of stent fracture was 30.4% in the left anterior descending coronary artery, 10.9% in the left circumflex coronary artery, 56.4% in the right coronary artery, < 0.01% in the left main coronary artery, and 1.7% in saphenous vein grafts. The probability of stent fracture was significantly higher in the right coronary artery than in the left anterior descending and left circumflex lesions (p < 0.01). Left main stents were less likely to fracture compared to those in all other vessels (p < 0.01). The probability of stent fracture was significantly increased in overlapping stents (7.5% vs 2.1%, p = 0.01) and long stents (46 vs 32.5 mm, p < 0.01). Lesions with stent fractures had higher rates of ISR (38% vs 8.2%, p < 0.01) and TLR (17% vs 5.6%, p < 0.01). Conversely, the probability of stent fractures was higher in patients with ISR (12.8% vs 2.1%, p < 0.01) and TLR (8.8% vs 2.7%, p < 0.01). In conclusion, although not always associated with clinical sequelae, the probability of ISR and TLR is increased with stent fracture. Conversely, the probability of stent fractures is increased in lesions with ISR or TLR, thus raising the need for surveillance and management guidelines for at-risk patients.
Publisher: Georg Thieme Verlag KG
Date: 2007
DOI: 10.1160/TH06-08-0467
Publisher: Elsevier BV
Date: 12-2017
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.AMJCARD.2010.06.010
Abstract: A meta-analysis of published studies was conducted to evaluate the incidence, predictors, and clinical outcomes of stent fractures. Eight studies with 108 stent fractures in 5,321 patients were analyzed using the Bayesian method. Study end points included in-stent restenosis (ISR) and target lesion revascularization (TLR). The mean incidence of stent fracture per patient was 4.0% (95% confidence interval 0.4% to 16.3%). All cases, except 1, were reported with sirolimus-eluting stents. The incidence of stent fracture was 30.4% in the left anterior descending coronary artery, 10.9% in the left circumflex coronary artery, 56.4% in the right coronary artery, < 0.01% in the left main coronary artery, and 1.7% in saphenous vein grafts. The probability of stent fracture was significantly higher in the right coronary artery than in the left anterior descending and left circumflex lesions (p < 0.01). Left main stents were less likely to fracture compared to those in all other vessels (p < 0.01). The probability of stent fracture was significantly increased in overlapping stents (7.5% vs 2.1%, p = 0.01) and long stents (46 vs 32.5 mm, p < 0.01). Lesions with stent fractures had higher rates of ISR (38% vs 8.2%, p < 0.01) and TLR (17% vs 5.6%, p < 0.01). Conversely, the probability of stent fractures was higher in patients with ISR (12.8% vs 2.1%, p < 0.01) and TLR (8.8% vs 2.7%, p < 0.01). In conclusion, although not always associated with clinical sequelae, the probability of ISR and TLR is increased with stent fracture. Conversely, the probability of stent fractures is increased in lesions with ISR or TLR, thus raising the need for surveillance and management guidelines for at-risk patients.
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.JCIN.2008.10.010
Abstract: Meta-analyses of intracoronary autologous bone marrow cell infusion in patients with acute myocardial infarction establish the procedure as safe. Nonetheless, the typical small increase in ejection fraction is of uncertain clinical significance, with little if any evidence of myocardial regeneration. In this paper, we describe 3 new paradigms of myocardial preservation and regeneration that provide reasonable hope that the goal of myocardial rejuvenation can be achieved. The first paradigm is that substantial preservation of myocardium is possible even during the period of coronary occlusion and immediate reperfusion, before interventions aimed at myocardial regeneration. The factors that induce myocardial preservation may also create an environment more receptive to subsequent myocardial regeneration. The second paradigm is that the local environment may regulate the behavior of cells in the ischemic/infarct region. For instance, adult cells may be induced to re-enter the cell cycle and proliferate with appropriate environmental modification. The final paradigm is that autologous cardiac stem cells or induced pluripotent stem cells can create new myocytes and myocardium. Taken together, these new ideas, each still to be proven, suggest that the goal of regenerating functioning new myocardium can still be achieved.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.AMJCARD.2010.09.029
Abstract: The American College of Cardiology/American Heart Association recently updated recommendations for percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) disease from class III to II(b) according to the results of the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial. The SYNTAX score is an angiographic tool using solely the coronary anatomy. We studied the effect of co-morbidities (Parsonnet's score) on the ability of the SYNTAX score to predict long-term outcomes in patients with ULMCA disease treated by revascularization. A total of 328 patients underwent revascularization of ULMCA from April 2003 to February 2007. Of the 328 patients, 120 underwent PCI (median follow-up 973 days) and 208 underwent coronary artery bypass grafting (CABG) (median follow-up 1,298 days). The ability of the SYNTAX score to predict outcomes was assessed using the Cox proportional hazards model. The outcomes between the PCI and CABG groups were compared by propensity analysis. The median SYNTAX score was 26 in the PCI and 28 in the CABG group (p = 0.5). In the PCI group, greater quartiles were associated with worse survival (62.1% at SYNTAX score of ≥36 vs 82.4% at SYNTAX score of <36, p = 0.03) and all-cause mortality, myocardial infarction, cerebrovascular events, and target vessel revascularization-free (MACCE) survival (47.7%, SYNTAX score ≥20 vs 76.6%, SYNTAX score <20, p = 0.02). Using the Parsonnet score as a covariate, the SYNTAX score continued to be an independent predictor of MACCE and demonstrated a trend toward predicting mortality in the PCI group. In contrast, the SYNTAX score did not predict the outcomes for the CABG group. No difference was found in mortality between the PCI and CABG groups for ULMCA disease, regardless of coronary complexity although greater SYNTAX scores were associated with increased MACCE rates with PCI compared to CABG. Both the coronary anatomy (SYNTAX score) and co-morbidities (Parsonnet's score) predicted long-term outcomes for PCI of ULMCA disease. In contrast, the SYNTAX score did not predict the outcomes after CABG. In conclusion, the ideal scoring system to guide an appropriate revascularization decision for ULMCA disease should take into account both the coronary anatomy and the co-morbidities.
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.JCIN.2008.02.007
Abstract: The purpose of this study was to compare outcomes for drug-eluting stents (DES) and coronary artery bypass graft (CABG) surgery in patients with unprotected left main coronary artery (ULMCA) stenosis. Expert guidelines recommend coronary artery bypass graft (CABG) surgery for the treatment of significant stenosis of the unprotected left main coronary artery (ULMCA) if the patient is eligible for CABG however, treatment by percutaneous coronary intervention (PCI) is common. Details of patients (n = 343, ages 69.9 +/- 11.9 years) undergoing coronary revascularization for ULMCA stenosis (April 2003 to January 2007) were recorded. A total of 223 patients were treated with CABG (mean [interquartile range]: follow-up 600 [226 to 977) days) and 120 by PCI (follow-up 362 [192 to 586) days). The hazard ratios (HRs) for death and major adverse cardiovascular and cerebrovascular events (MACCE) were calculated incorporating propensity score adjustment. Survival comparisons were conducted in propensity-matched subjects (n = 134), and in low- and high-risk subjects for CABG. Patients treated by PCI were more likely to be >or=75 years of age (49% vs. 33% p = 0.005), and of greater surgical risk (Parsonnet score 17.2 +/- 11.2 vs. 13.0 +/- 9.3 p < 0.001) than patients treated by CABG. Overall, the propensity-adjusted HR for death was not statistically different (HR 1.93, 95% confidence interval [CI] 0.89 to 4.19, p = 0.10), but MACCE was greater in the PCI group (HR 1.83, 95% CI 1.01 to 3.32, p = 0.05). In propensity-matched in iduals, neither survival nor MACCE-free survival were different. Survival was equivalent among low-risk candidates, but PCI had a tendency to inferior survival in high-risk candidates (Ellis category IV, log-rank p = 0.05). Interaction testing, however, failed to demonstrate a difference in outcomes of the 2 revascularization techniques as a function of baseline risk assessment. Overall, the propensity-adjusted risk of mortality for treatment of ULMCA disease does not differ between PCI- and CABG-treated groups. There appears to be sufficient equipoise that a randomized clinical trial to compare the techniques would not be ethically contraindicated.
Publisher: Oxford University Press (OUP)
Date: 09-2007
DOI: 10.1016/J.CARDIORES.2007.05.003
Abstract: Matrix metalloproteinases (MMPs) are plausible candidates for prediction of unstable coronary syndromes. We hypothesised that the MMP-3 polymorphism (- 1171, 5A/6A) would relate to coronary plaque characteristics and unstable clinical presentation. Forty patients with de novo presentation of coronary artery disease (CAD) were classified into unstable coronary syndrome (n=19) or stable angina pectoris (n=21). On coronary intravascular ultrasound, patients with unstable disease had a greater plaque burden, more positive (outward) coronary remodelling, and all but one were MMP-3 6A allele carriers (p=0.027 compared with stable). The relationship between the 6A allele and unstable presentation was substantiated in a validation cohort of 161 CAD patients (58 stable and 103 unstable) and in the total population of 201 CAD patients (79 stable and 122 unstable, p=0.007), and was independent of conventional risk factors. Furthermore, 6A allele carriers had a higher plasma MMP-3 concentration (15.8+/-12.5 versus 11.7+/-7.2 ng/mL, p=0.01), maximum coronary stenosis on angiography (89+/-15% versus 80+/-23%, p=0.02), plaque area (12.0+/-5.2 versus 7.5+/-3.6 mm(2), p=0.03), percentage plaque burden (82+/-7 versus 71+/-13%, p=0.003), and remodelling ratio (1.03+/-0.23 versus 0.83+/-0.12, p=0.003). The MMP-3 6A allele promotes positive coronary remodelling, greater plaque burden, and increased susceptibility to unstable coronary syndromes in humans.
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.JCIN.2009.05.020
Abstract: This study sought to understand the total weight of evidence regarding outcomes in coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in unprotected left main coronary artery (ULMCA) stenosis. Following a diagnosis of significant ULMCA stenosis in an in idual that is a candidate for surgery, CABG is recommended by the American College of Cardiology/American Heart Association guidelines, whereas PCI is not recommended (Class III). Databases were searched for clinical studies that reported outcomes after PCI and CABG for the treatment of ULMCA stenosis. Ten studies were identified that included a total of 3,773 patients. Meta-analysis showed that death, myocardial infarction, and stroke (major adverse cardiovascular or cerebrovascular events) were similar in the PCI- and CABG-treated patients at 1 year (odds ratio [OR]: 0.84 [95% confidence interval: 0.57 to 1.22]), 2 years (OR: 1.25 [95% CI: 0.81 to 1.94]), and 3 years (OR: 1.16 [95% CI: 0.68 to 1.98]). Target vessel revascularization was significantly higher in the PCI group at 1 year (OR: 4.36 [95% CI: 2.60 to 7.32]), 2 years (OR: 4.20 [95% CI: 2.21 to 7.97]), and 3 years (OR: 3.30 [95% CI: 0.96 to 11.33]). There was no difference in mortality in PCI- versus CABG-treated patients at 1 year (OR: 1.00 [95% CI: 0.70 to 1.41]), 2 years (OR: 1.27 [95% CI: 0.83 to 1.94]), and 3 years (OR: 1.11 [95% CI: 0.66 to 1.86]). Our analysis reveals no difference in mortality or major adverse cardiovascular or cerebrovascular events, for up to 3 years, between PCI and CABG for the treatment of ULMCA stenosis. However, PCI patients had a significantly higher risk of target vessel revascularization. In selected patients with ULMCA stenosis, PCI is emerging as an acceptable option.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.SCR.2014.04.016
Abstract: The study of human cardiogenesis would benefit from a detailed cell lineage fate map akin to that established for the haematopoietic lineages. Here we sought to define cell lineage relationships based on the expression of NKX2-5 and the cell surface markers VCAM1, SIRPA and CD34 during human cardiovascular development. Expression of NKX2-5(GFP) was used to identify cardiac progenitors and cardiomyocytes generated during the differentiation of NKX2-5(GFP/w) human embryonic stem cells (hESCs). Cardiovascular cell lineages sub-fractionated on the basis of SIRPA, VCAM1 and CD34 expression were assayed for differentiation potential and gene expression. The NKX2-5(pos)CD34(pos) population gave rise to endothelial cells that rapidly lost NKX2-5 expression in culture. Conversely, NKX2-5 expression was maintained in myocardial committed cells, which progressed from being NKX2-5(pos)SIRPA(pos) to NKX2-5(pos)SIRPA(pos)VCAM1(pos). Up-regulation of VCAM1 was accompanied by the expression of myofilament markers and reduced clonal capacity, implying a restriction of cell fate potential. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. These markers identify specific stages of cardiomyocyte and endothelial lineage commitment and, thus provide a scaffold for establishing a fate map of early human cardiogenesis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
Publisher: Public Library of Science (PLoS)
Date: 25-09-2009
No related grants have been discovered for Anthony White.