ORCID Profile
0000-0002-3919-5269
Current Organisation
University of Newcastle Australia
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Publisher: Springer Science and Business Media LLC
Date: 09-2010
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.CARREV.2010.06.003
Abstract: 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.
Publisher: Wiley
Date: 12-2004
DOI: 10.1111/J.1445-5994.2004.00698.X
Abstract: 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.
Publisher: Springer US
Date: 07-11-2011
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.IJCARD.2009.03.098
Abstract: Effect of HMGCoA Reductase Inhibitors on Cardiac Remodelling and Mortality in Rats. Following Hyperglycemia and Myocardial Infarction. The presence of diabetes mellitus (DM) in patients with myocardial infarction (MI) increases mortality, due in part to the presence of known cardiovascular risk factors. However little is known about the impact of DM on cardiac remodelling and on clinical outcomes. We aimed to investigate whether hyperglycaemia may adversely and additionally affect LV remodelling post-MI, and whether the addition of a statin, known to reduce mortality both post MI and in humans with DM, has an effect on these outcomes. Eight week old Sprague-Dawley rats were allocated to 5 groups--control (non-DM)/sham, control-MI, DM-sham, DM-MI and DM-MI with statin gavage (DM-MI/ATV). Echocardiogram and invasive pressure volume analysis were performed prior to sacrifice for estimation of cardiac function. Tissue was analysed for total cardiac collagen, collagen I and III. Hyperglycaemia in the remodelling period significantly increased mortality (70% survival in the C-MI group vs 27% in the DM-MI group), worsened cardiac function and increased fibrosis. All of these variables were attenuated by the addition of a statin. Hyperglycaemia increased mortality in MI and exacerbated LV remodeling, and this was attenuated with statin use. This study confirms the importance of early and intensive treatment of hyperglycaemia in patients with MI and suggests that in humans with both DM and MI the addition of a statin may be beneficial.
Publisher: Wiley
Date: 26-03-2007
DOI: 10.1111/J.1540-8183.2007.00242.X
Abstract: 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. 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. 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. 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.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Springer Berlin Heidelberg
Date: 2007
DOI: 10.1007/978-3-540-68976-8_9
Abstract: 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.
Publisher: Springer Science and Business Media LLC
Date: 12-09-2011
Publisher: Springer Science and Business Media LLC
Date: 30-01-2020
DOI: 10.1007/S12265-020-09955-W
Abstract: Midkine (MK) is a heparin-binding growth factor, whose role as a biomarker of coronary artery disease, myocardial ischaemia and necrosis has not been well measured. This study quantified serial MK levels in patients undergoing coronary angiography (CA) and identified factors associated with MK. In this single-centre, parallel cohort study, forty patients undergoing CA had arterial s les collected prior, 10 and 20 min after heparin administration. Four groups were examined: 1-stable coronary artery disease (CAD) without percutaneous coronary intervention (PCI) 2-stable CAD for elective PCI 3-non-ST elevation myocardial infarction (NSTEMI) with or without PCI 4-ST elevation myocardial infarction (STEMI) with primary PCI. Groups 1, 2 and 4 were heparin naïve, allowing assessment of the effects of myocardial necrosis between baseline levels group 3 had received low-molecular-weight heparin. MK levels were analysed by ELISA. Median MK at baseline did not differ between groups, demonstrating that myocardial ischaemia or necrosis does not affect MK levels. Heparin administration had an immediate effect on median MK at 10 min, showing an average 500-fold increase that is dose-dependent (R
Publisher: Elsevier BV
Date: 2001
DOI: 10.1046/J.1444-2892.2001.00099.X
Abstract: 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-08-2010
DOI: 10.1002/LT.22152
Abstract: 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.
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.JACC.2006.06.073
Abstract: The purpose of this study was to test the hypothesis, with noninvasive multimodality imaging, that allogeneic mesenchymal stem cells (MSCs) produce and/or stimulate active cardiac regeneration in vivo after myocardial infarction (MI). Although intramyocardial injection of allogeneic MSCs improves global cardiac function after MI, the mechanism(s) underlying this phenomenon are incompletely understood. We employed magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) imaging in MSC-treated pigs (n = 10) and control subjects (n = 12) serially for a 2-month period after anterior MI. A sub-endocardial rim of tissue, demonstrated with MDCT, was assessed for regional contraction with MRI tagging. Rim thickness was also measured on gross pathological specimens, to confirm the findings of the MDCT imaging, and the size of cardiomyocytes was measured in the sub-endocardial rim and the non-infarct zone. Multi-detector computed tomography demonstrated increasing thickness of sub-endocardial viable myocardium in the infarct zone in MSC-treated animals (1.0 +/- 0.2 mm to 2.0 +/- 0.3 mm, 1 and 8 weeks after MI, respectively, p = 0.028, n = 4) and a corresponding reduction in infarct scar (5.1 +/- 0.5 mm to 3.6 +/- 0.2 mm, p = 0.044). No changes occurred in control subjects (n = 4). Tagging MRI demonstrated time-dependent recovery of active contractility paralleling new tissue appearance. This rim was composed of morphologically normal cardiomyocytes, which were smaller in MSC-treated versus control subjects (11.6 +/- 0.2 mum vs. 12.6 +/- 0.2 mum, p < 0.05). With serially obtained MRI and MDCT, we demonstrate in vivo reappearance of myocardial tissue in the MI zone accompanied by time-dependent restoration of contractile function. These data are consistent with a regenerative process, highlight the value of noninvasive multimodality imaging to assess the structural and functional basis for myocardial regenerative strategies, and have potential clinical applications.
Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.IJCARD.2005.05.024
Abstract: 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.
Publisher: Georg Thieme Verlag KG
Date: 2004
DOI: 10.1055/S-2003-45236
Abstract: 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 (cTnI) 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 cTnI 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 cTnI were undetectable post-race in 14 athletes with a level of 0.9 microg/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.
Publisher: Humana Press
Date: 2010
DOI: 10.1007/978-1-60761-705-1_5
Abstract: 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.
Publisher: Elsevier BV
Date: 12-2014
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.CARREV.2013.08.009
Abstract: 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. 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. 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). IA vasodilators increase pre-procedural RA diameter in patients undergoing cardiac catheterization via TRA. This increase in diameter has important implications for procedural planning. 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.
Publisher: Elsevier BV
Date: 02-2012
Publisher: American Physiological Society
Date: 05-2008
DOI: 10.1152/AJPHEART.00762.2007
Abstract: 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.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.AMJCARD.2008.10.037
Abstract: 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 x 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.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.HLC.2012.08.054
Abstract: Tranilast has been shown to inhibit TGFβ1-related fibrosis and organ failure in various disease models. We sought to examine the effects of tranilast on left ventricular (LV) remodelling post-MI. Following coronary artery ligation, Sprague Dawley rats were randomised to receive tranilast (300mg/kg/d, p.o.) or vehicle control over one of two treatment periods: (1) from 24h 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. Tranilast treatment of MI rats from 24h until seven days post-MI reduced myocardial collagen content, α1 (I) procollagen, TGFβ1 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 α1(I) procollagen, α1(III) procollagen, fibronectin, TGFβ1 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 TGFβ1-stimulated fibrogenesis. Tranilast inhibits myocardial TGFβ1 expression, fibrosis in rat post-MI and collagen production in cardiac fibroblasts. While tranilast intervention from 24h post-MI exacerbated infarct expansion, delaying the commencement of treatment to seven days post-MI impeded LV remodelling.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.JACC.2011.10.853
Abstract: This study assessed the comparative effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) among patients ≥85 years of age. 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). 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. 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). In contrast, the adjusted HR for myocardial infarction rehospitalization associated with DES use was 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). 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.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.JCRC.2012.04.019
Abstract: Small radial artery diameter (RAD) and vasospasm are barriers to radial artery cannulation. We performed this study to determine if topical nitroglycerin and/or nitroglycerin plus topical lidocaine increases RAD without affecting systemic blood pressure. This was a randomized, double-blind, placebo-controlled study. In the first visit, to determine the optimal dose of nitroglycerin, subjects were randomized to either 15 or 30 mg nitroglycerin on one wrist and placebo on the other. In visit 2, to assess for any effect of lidocaine on the vasodilator function of nitroglycerin, the same subjects were randomized to 20 mg lidocaine + 30 mg nitroglycerin vs 20 mg lidocaine + placebo, or 40 mg lidocaine + 30 mg nitroglycerin vs 40 mg lidocaine + placebo. In both visits, blood pressure and RAD using ultrasonography were measured for 2 hours. In visit 1, both nitroglycerin groups significantly increased RAD, with greater increases with 30 mg nitroglycerin (P < .01) and no significant increase in RAD in placebo wrists. In visit 2, increase in RAD was significantly greater with 20 mg lidocaine + 30 mg nitroglycerin vs 20 mg lidocaine + placebo (P < .001), and 40 mg lidocaine + 30 mg nitroglycerin vs 40 mg lidocaine + placebo (P < .001), indicating that lidocaine does not alter the effect of nitroglycerin. There were significant increases in RAD seen as early as 30 minutes. There were no significant change in RAD in lidocaine + placebo-treated wrists and no change in blood pressure in any group. Topical nitroglycerin and lidocaine significantly increase RAD within 30 to 60 minutes with no effect on contralateral radial artery or blood pressure, indicating a direct, local effect on the radial artery. (Clinicaltrials.gov number NCT00686231).
Publisher: Elsevier BV
Date: 07-2011
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.CARREV.2012.12.007
Abstract: 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.
Publisher: Wiley
Date: 27-11-2013
Publisher: Springer New York
Date: 2014
Publisher: Bentham Science Publishers Ltd.
Date: 09-2007
DOI: 10.2174/138161207781662984
Abstract: 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.
Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.YJMCC.2005.11.013
Abstract: 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.
Publisher: Oxford University Press (OUP)
Date: 08-06-2022
Abstract: Dietary modification is essential for the secondary prevention of cardiovascular disease. However, there are limited published evidence syntheses to guide practice in the cardiac rehabilitation (CR) setting. This systematic review's objective was to assess effectiveness and reporting of nutrition interventions to optimize dietary intake in adults attending CR. Randomized controlled trials (RCTs) of nutrition interventions within CR were eligible for inclusion and had to have measured change in dietary intake. MEDLINE, Embase, Emcare, PsycINFO, CINAHL, Scopus, and The Cochrane Library were searched from 2000 to June 2020, limited to publications in English. Evidence from included RCTs was synthesized descriptively. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool. This review is registered on PROSPERO CRD42020188723. Of 13 048 unique articles identified, 11 were eligible. Randomized controlled trials were conducted in 10 different countries, included 1542 participants, and evaluated 29 distinct dietary intake outcomes. Five studies reported statistically significant changes in diet across 13 outcomes. Most nutrition interventions were not reported in a manner that allowed replication in clinical practice or future research. There is a gap in research testing high-quality nutrition interventions in CR settings. Findings should be interpreted in the light of limitations, given the overall body of evidence was heterogenous across outcomes and study quality 6 of 11 studies were conducted more than 10 years old. Future research should investigate strategies to optimize and maintain nutrition improvements for patients attending CR. PROSPERO CRD42020188723.
Publisher: ASME International
Date: 08-2015
DOI: 10.1115/1.4030667
Abstract: 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 C0¯=0.102 kPa, and a remote myocardial contractility of Tmax¯=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.
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.CYTO.2010.06.003
Abstract: 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. 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 microg/kg at time of reperfusion, followed by SC injections of 5 microg/kg days 5-9 post-MI) or saline (control group). Inflammatory markers, bone marrow cell mobilization and LV function (echocardiography and pressure-volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI. 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). 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.
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.AMJCARD.2008.05.064
Abstract: Perfusion assessed in the cardiac catheterization laboratory predicts outcomes after myocardial infarction. The aim of this study was to investigate a novel method of assessing perfusion using digital subtraction angiography to generate a time-density curve (TDC) of myocardial blush, incorporating epicardial and myocardial perfusion. Seven pigs underwent temporary occlusion of the left anterior descending coronary artery for 60 minutes. Angiography was performed in the same projections before, during, and after occlusion. Perfusion parameters were obtained from the TDC and compared with Thrombolysis In Myocardial Infarction (TIMI) frame count and myocardial perfusion grade. In addition, safety and feasibility were tested in 8 patients after primary percutaneous coronary intervention. The contrast density differential between the proximal artery and the myocardium derived from the TDC correlated well with TIMI myocardial perfusion grade (R = 0.54, p <0.001). The arterial transit time derived from the TDC correlated with TIMI frame count (R = 0.435, p = 0.011). Using a cutoff of 2.4, the density/time ratio, a ratio of density differential to transit time, had sensitivity and specificity of 100% for coronary arterial occlusion. The positive and negative predictive values were 100%. The generation of a TDC was safe and feasible in 7 patients after acute myocardial infarctions, but the correlation between TDC-derived parameters and TIMI parameters did not reach statistical significance. In conclusion, this novel method of digital subtraction angiography with rapid, automated, quantitative assessment of myocardial perfusion in the cardiac catheterization laboratory correlates well with established angiographic measures of perfusion. Further studies to assess the prognostic value of this technique are warranted.
Publisher: Informa UK Limited
Date: 12-04-2012
DOI: 10.3109/07853890.2012.672026
Abstract: 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. 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. 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. Clinical studies should be performed to test whether whole BMC therapy translates into better outcome also after human MI.
Publisher: Wiley
Date: 20-11-2006
DOI: 10.1002/CCD.20880
Abstract: Coronary air embolism is a complication in the catheterization laboratory that can be associated with high morbidity and even mortality. A case report of air embolism and methods to prevent this complication from occurring are presented along with various management techniques.
Publisher: Bentham Science Publishers Ltd.
Date: 17-04-2012
DOI: 10.2174/1874192401206010038
Abstract: 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. 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. hBMC and hMNC extract preserve cardiac function and result in smaller scar size post-MI when compared with the control group. 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.
Publisher: Bentham Science Publishers Ltd.
Date: 2010
DOI: 10.2174/157016110790226688
Abstract: 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.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.HLC.2022.09.017
Abstract: Australia's First Nations Peoples, Aboriginal and Torres Strait Islanders, have reduced life expectancy compared to the wider community. Cardiovascular diseases, mainly driven by ischaemic heart disease, are the leading contributors to this disparity. Despite over a third of First Nations Peoples living in New South Wales, the bulk of the peer-reviewed literature is from Central Australia and Far North Queensland. Regardless of the site of publication, First Nations Peoples are significantly younger at disease onset and have higher rates of comorbidities, in turn driving adverse health events. On top of this, very few First Nations Peoples specific cardiovascular interventions or programs have been shown to improve outcomes. The traditional biomedical model of care is less efficacious and non-traditional models of communication such as clinical yarning may benefit both clinicians and patients. The key purpose of this review is to highlight the deficiencies of our knowledge of cardiovascular burden of disease for First Nations Peoples and to serve as a catalyst for more dedicated research. We need to have relationships with communities and concentrate on community improvement and partnerships. By involving First Nations Peoples researchers in collaboration with local communities in all levels of health care design and intervention will improve outcomes.
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1038/MT.2009.85
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-07-2006
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.HLC.2018.04.304
Abstract: Myocardial perfusion scanning (MPS) is commonly used to assess patients with an intermediate to high risk of coronary artery disease. Concerns have been raised about the accuracy of this test. There is little recent data regarding the specificity of the MPS in the context of current medical therapy. The primary objective of this study is to determine the specificity of MPS in diagnosing obstructive coronary artery disease. A total of 184 patients fulfilled study criteria. The overall specificity of MPS for obstructive coronary artery disease was 54%.The only demographic variable that influenced specificity was gender: males with a specificity of 66% and females with a specificity of 29% (p-value=0.001). These results suggest that the real world specificity of MPS is lower than previously indicated, particularly in the female population. The limitations proposed by the Cardiac Services Committee Report are therefore unlikely to improve patient outcomes.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.CARDFAIL.2010.03.008
Abstract: 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. 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, at 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. 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2010
DOI: 10.1161/CIRCRESAHA.110.222703
Abstract: The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow–derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes. Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire. Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow–derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit + CSCs increased 20-fold in MSC-treated animals versus controls ( P .001), there was a 6-fold increase in GATA-4 + CSCs in MSC versus control ( P .001), and mitotic myocytes increased 4-fold ( P =0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit + CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2–5 and troponin I. MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.
Publisher: Elsevier BV
Date: 07-2002
DOI: 10.1016/S0300-9572(02)00049-7
Abstract: 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.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.CARDFAIL.2010.02.008
Abstract: 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. 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). 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.
Publisher: Elsevier BV
Date: 2011
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.IJCARD.2005.01.068
Abstract: 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.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.HLC.2018.02.022
Abstract: There is conflicting information regarding the contemporary incidence of first acute myocardial infarction (AMI) in Australia. We sought to document the regional variations in first AMI incidence in a large health district. We identified all patients presenting with first AMI in the Hunter region of New South Wales from 2004 to 2013. We calculated age and gender adjusted incidence of AMI and evaluated differences between patients from regional and metropolitan areas. We assessed 30-day and 12-month outcomes, including mortality, through linkage with the NSW Registry of Births Deaths and Marriages. The incidence of first AMI in regional areas was persistently higher throughout the study compared to metropolitan areas (IRR 1.244 95% CI 1.14-1.35 p≤0.001). There were no significant differences between regional and metropolitan areas in 30-day and 12-month outcomes following presentation with first AMI. The study demonstrates persistently higher rates in regional compared to metropolitan areas, supporting the need for implementation of targeted intervention and prevention strategies.
Publisher: Rockefeller University Press
Date: 13-12-2004
DOI: 10.1084/JEM.20040221
Abstract: Human adult bone marrow–derived endothelial progenitors, or angioblasts, induce neovascularization of infarcted myocardium via mechanisms involving both cell surface urokinase-type plasminogen activator, and interactions between β integrins and tissue vitronectin. Because each of these processes is regulated by plasminogen activator inhibitor (PAI)-1, we selectively down-regulated PAI-1 mRNA in the adult heart to examine the effects on postinfarct neovascularization and myocardial function. Sequence-specific catalytic DNA enzymes inhibited rat PAI-1 mRNA and protein expression in peri-infarct endothelium within 48 h of administration, and maintained down-regulation for at least 2 wk. PAI-1 inhibition enhanced vitronectin-dependent transendothelial migration of human bone marrow–derived CD34+ cells, and resulted in a striking augmentation of angioblast-dependent neovascularization. Development of large, thin-walled vessels at the peri-infarct region was accompanied by induction of proliferation and regeneration of endogenous cardiomyocytes and functional cardiac recovery. These results identify a causal relationship between elevated PAI-1 levels and poor outcome in patients with myocardial infarction through mechanisms that directly inhibit bone marrow–dependent neovascularization. Strategies that reduce myocardial PAI-1 expression appear capable of enhancing cardiac neovascularization, regeneration, and functional recovery after ischemic insult.
Publisher: Hindawi Limited
Date: 16-05-2019
DOI: 10.1155/2019/1010243
Abstract: Background . Takotsubo syndrome is a reversible heart failure syndrome which often presents with symptoms and ECG changes that mimic an acute myocardial infarction. Obstructive coronary artery disease has traditionally been seen as exclusion criteria for the diagnosis of takotsubo however, recent reports have called this into question and suggest that the two conditions may coexist. Case Summary . We describe a case of an 83-year-old male presenting with chest pain consistent with acute myocardial infarction. The ECG demonstrated anterior ST elevation with bedside echocardiography showing apical wall motion abnormalities. Cardiac catheterisation found an occluded OM2 branch of the left circumflex artery with ventriculography confirming apical ballooning consistent with takotsubo and not in the vascular territory supplied by the occluded epicardial vessel. Repeat echocardiogram 6 weeks later confirmed resolution of the apical wall motion abnormalities consistent with a diagnosis of takotsubo. Discussion . This case demonstrates the finding of takotsubo syndrome in a male patient with acute myocardial infarction. Traditionally, this would preclude a diagnosis of takotsubo however, following previous reports of takotsubo in association with coronary artery dissection and acute myocardial infarction in female patients, new diagnostic criteria have been proposed which allow the diagnosis of takotsubo in the presence of obstructive coronary artery disease. This case adds to the growing body of literature that suggests takotsubo can coexist with acute myocardial infarction however, it remains to be elucidated if it is a consequence or cause of myocardial infarction.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.HLC.2018.01.009
Abstract: Heart failure (HF) is a common, costly condition with an increasing burden on Australian health care system resources. Knowledge of the burden of HF on patients and on the health system is important for resource allocation. This study is the first systematic review to estimate the mortality and readmission rates after hospitalisation for HF in the Australian population. We searched for studies of HF hospitalisation in Australia published between January 1990 and May 2016, using a systematic search of PubMed, Medline, Scopus, Web of Science, EMBASE and Cochrane Library databases. Studies reporting 30-day and/or 1-year outcomes for mortality or readmission following hospitalisation were eligible and included in this study. Out of 2889 articles matching the initial search criteria, a total of 13 studies representing 67,255 patients were included in the final analysis. The pooled mean age of heart failure patients was 76.3 years and 51% were male (n=34,271). The pooled estimated 30-day and 1-year all-cause mortality were 8% and 25% respectively. The pooled estimated 30-day and 1-year all-cause readmission rates were 20% and 56% respectively. There is a high prevalence of comorbidities in heart failure patients. There were limited data on readmission and mortality in rural patients and Indigenous people. Heart failure hospitalisations in Australia are followed by substantial readmission and mortality rates.
Publisher: Public Library of Science (PLoS)
Date: 17-01-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.CARPATH.2010.06.007
Abstract: Bone marrow cell treatment has been proposed as a therapy for myocardial infarction, but the optimal timing and number of injections remain unknown. 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. 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. 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.
Publisher: Elsevier BV
Date: 2003
DOI: 10.1046/J.1444-2892.2003.00165.X
Abstract: 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.
Publisher: American Physiological Society
Date: 07-2011
DOI: 10.1152/AJPLUNG.00215.2010
Abstract: 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.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.HLC.2018.03.011
Abstract: The most frequent complications from percutaneous electrophysiology procedures relate to vascular access. We sought to perform the first randomised controlled trial for femoral venous haemostasis utilising a simple and novel purse string suture (PSS) technique. We randomised 200 consecutive patients who were referred for electrophysiology procedures at two different hospitals to either 10minutes of manual pressure or a PSS over the femoral vein and determined the incidence of vascular access site complications. The mean age was 61.8±12.1years and 138 (69%) were male. Bleeding requiring addition pressure or a FemStop (Abbott Laboratories, Abbott Park, IL, USA) for complete haemostasis occurred in 17/99 (17%) patients in the PSS arm and 19/101 (19%) patients in the manual pressure arm (p=0.72). There were no cases of haematoma prolonging hospital stay, arterio-venous fistula, pseudoaneurysm or retroperitoneal bleeding. The mean duration to achieve haemostasis was 45seconds in the PSS arm and 10minutes 44seconds in the manual pressure arm (p<0.001). Pain/discomfort associated with haemostasis occurred in 15/99 (15%) patients in the PSS arm and in 29/101 (29%) patients receiving manual pressure (p=0.03). In this randomised trial we demonstrate that an easy to perform PSS is as effective at achieving haemostasis as 10minutes of manual pressure for catheter ablation procedures. The PSS is considerably faster to perform and is more comfortable for patients than manual pressure.
Publisher: Springer Science and Business Media LLC
Date: 07-02-2010
Publisher: Wiley
Date: 02-09-2011
Publisher: Oxford University Press (OUP)
Date: 29-07-2015
DOI: 10.1002/STEM.2101
Abstract: 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, PDGFRα, 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. Stem Cells 2015 :3100–3113
Publisher: MDPI AG
Date: 23-09-2013
DOI: 10.3390/JCM2030103
Publisher: Elsevier BV
Date: 06-2001
Publisher: Springer New York
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 13-10-2012
DOI: 10.1007/S00441-012-1511-8
Abstract: 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.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.JACC.2010.03.039
Abstract: 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). Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function. 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. 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. 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).
Publisher: Elsevier BV
Date: 11-2005
Publisher: Elsevier BV
Date: 08-2023
Publisher: Elsevier BV
Date: 08-2005
DOI: 10.1016/J.YJMCC.2005.03.008
Abstract: 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 underlying 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.
Publisher: Springer Science and Business Media LLC
Date: 29-12-2015
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.IJCARD.2013.03.048
Abstract: 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. 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. 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. Pre-procedural administration of topical mixture of nitroglycerin+lidocaine increases the size of the radial artery in patients undergoing transradial cardiac catheterization. NCT01155167.
Location: United States of America
No related grants have been discovered for Andrew Boyle.