ORCID Profile
0000-0003-0222-5468
Current Organisations
Queen Elizabeth Hospital
,
Royal Adelaide Hospital
,
University of Adelaide
,
South Australian Health and Medical Research Institute
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JCMG.2017.04.010
Abstract: This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients with coronary artery disease who were treated with and without warfarin. Warfarin blocks the synthesis and activity of matrix Gla protein, a vitamin K-dependent inhibitor of arterial calcification. The longitudinal impact of warfarin on serial coronary artery calcification in vivo in humans is unknown. In a post hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound examinations, this study compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease who were treated with (n = 171) and without (n = 4,129) warfarin during an 18- to 24-month period. Patients (mean age 57.9 ± 9.2 years male 73% prior and concomitant 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin) use, 73% and 97%, respectively) demonstrated overall increases in PAV of 0.41 ± 0.07% (p = 0.001 compared with baseline) and in CaI (median) of 0.04 (interquartile range [IQR]: 0.00 to 0.11 p < 0.001 compared with baseline). Following propensity-weighted adjustment for clinical trial and a range of clinical, ultrasonic, and laboratory parameters, there was no significant difference in the annualized change in PAV in the presence and absence of warfarin treatment (0.33 ± 0.05% vs. 0.25 ± 0.05% p = 0.17). A significantly greater annualized increase in CaI was observed in warfarin-treated compared with non-warfarin-treated patients (median 0.03 IQR: 0.0 to 0.08 vs. median 0.02 IQR: 0.0 to 0.06 p < 0.001). In a sensitivity analysis evaluating a 1:1 matched cohort (n = 164 per group), significantly greater annualized changes in CaI were also observed in warfarin-treated compared with non-warfarin-treated patients. In a multivariate model, warfarin was independently associated with an increasing CaI (odds ratio: 1.16 95% confidence interval: 1.05 to 1.28 p = 0.003). Warfarin therapy is associated with progressive coronary atheroma calcification independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.
Publisher: SAGE Publications
Date: 2020
Abstract: Recent analyses suggest the incidence of acute coronary syndrome is declining in high- and middle-income countries. Despite this, overall rates of non-ST-elevation myocardial infarction (NSTEMI) continue to rise. Furthermore, NSTEMI is a greater contributor to mortality after hospital discharge than ST-elevation myocardial infarction (STEMI). Patients with NSTEMI are often older, comorbid and have a high likelihood of multivessel coronary artery disease (MVD), which is associated with worse clinical outcomes. Currently, optimal treatment strategies for MVD in NSTEMI are less well established than for STEMI or stable coronary artery disease. Specifically, in relation to percutaneous coronary intervention (PCI) there is a paucity of randomized, prospective data comparing multivessel and culprit lesion-only PCI. Given the heterogeneous pathological basis for NSTEMI with MVD, an approach of complete revascularization may not be appropriate or necessary in all patients. Recognizing this, this review summarizes the limited evidence base for the interventional management of non-culprit disease in NSTEMI by comparing culprit-only and multivessel PCI strategies. We then explore how a personalized, precise approach to investigation, therapy and follow up may be achieved based on patient-, disease- and lesion-specific factors.
Publisher: Wiley
Date: 02-2013
DOI: 10.1111/MICC.12022
Publisher: Elsevier BV
Date: 03-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-03-2014
DOI: 10.1161/CIRCULATIONAHA.113.006518
Abstract: The impact of changing demographics on causes of long-term death after percutaneous coronary intervention (PCI) remains incompletely defined. We evaluated trends in cause-specific long-term mortality after index PCI performed at a single center from 1991 to 2008. Deaths were ascertained by scheduled prospective surveillance. Cause was determined via telephone interviews, medical records, autopsy reports, and death certificates. Competing-risks analysis of cause-specific mortality was performed using 3 time periods of PCI (1991–1996, 1997–2002, and 2003–2008). Final follow-up was December 31, 2012. A total of 19 077 patients survived index PCI hospitalization, of whom 6988 subsequently died (37%, 4.48 per 100 person-years). Cause was determined in 6857 (98.1%). Across 3 time periods, there was a 33% decline in cardiac deaths at 5 years after PCI (incidence: 9.8%, 7.4%, and 6.6%) but a 57% increase in noncardiac deaths (7.1%, 8.5%, and 11.2%). Only 36.8% of deaths in the recent era were cardiac. Similar trends were observed regardless of age, extent of coronary disease, or PCI indication. After adjustment for baseline variables, there was a 50% temporal decline in cardiac mortality but no change in noncardiac mortality. The decline in cardiac mortality was driven by fewer deaths from myocardial infarction/sudden death ( P .001) but not heart failure ( P =0.85). The increase in noncardiac mortality was primarily attributable to cancer and chronic diseases ( P .001). This study found a marked temporal switch from predominantly cardiac to predominantly noncardiac causes of death after PCI over 2 decades. The decline in cardiac mortality was independent of changes in baseline clinical characteristics. These findings have implications for patient care and clinical trial design.
Publisher: BMJ
Date: 03-2018
DOI: 10.1136/HEARTJNL-2017-312579
Abstract: Coronary vasodilator function and atherosclerotic plaque progression have both been shown to be associated with adverse cardiovascular events. However, the relationship between these factors and the lipid burden of coronary plaque remains unknown. These experiments focus on investigating the relationship between impaired coronary vasodilator function (endothelium dependent (salbutamol) and endothelium independent (glyceryl trinitrate)) and the natural history of atheroma plaque progression and lipid burden using dual modality intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) imaging. 33 patients with stable chest pain or acute coronary syndrome underwent serial assessment of coronary vasodilator function and intracoronary plaque IVUS and NIRS imaging. Coronary segmental macrovascular response (% change segmental lumen volume (ΔSLV)), plaque burden (per cent atheroma volume (PAV)), lipid core (lipid-rich plaque (LRP) and lipid core burden index (LCBI)) were measured at baseline and after an interval of 12–18 months (n=520 segments). Lipid-negative coronary segments which develop into LRP over the study time period demonstrated impaired endothelial-dependent function (−0.24±2.96 vs 5.60±1.47%, P=0.04) and endothelial-independent function (13.91±4.45 vs 21.19±3.19%, P=0.036), at baseline. By multivariate analysis, endothelial-dependent function predicted ∆LCBI (β coefficient: −3.03, 95% CI (−5.81 to −0.25), P=0.033) whereas endothelial-independent function predicted ∆PAV (β coefficient: 0.07, 95% CI (0.04 to 0.10), P .0001). Epicardial coronary vasodilator function is a determinant of future atheroma progression and composition irrespective of the nature of clinical presentation. ACTRN12612000594820, Post-results.
Publisher: Elsevier BV
Date: 08-2017
Publisher: Wiley
Date: 29-01-2014
DOI: 10.1002/CCD.25368
Abstract: The management of refractory cardiac arrest during invasive coronary procedures has substantial logistical challenges and is typically associated with disappointing outcomes. We describe the case of a young woman with recalcitrant ventricular fibrillation due to acute anterior ST-elevation myocardial infarction caused by occlusion of her proximal left anterior descending artery. Survival without neurological deficit or organ failure was achieved following primary percutaneous reperfusion and a total of 52 min of intra-procedural chest compression support, made possible by the use of an automated chest compression device.
Publisher: Bentham Science Publishers Ltd.
Date: 15-07-2016
DOI: 10.2174/1573403X12666160606121858
Abstract: The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management.
Publisher: Wiley
Date: 03-2023
Abstract: Colchicine is a broad‐acting anti‐inflammatory agent that has attracted interest for repurposing in atherosclerotic cardiovascular disease. Here, we studied its ability at a human equivalent dose of 0.5 mg/day to modify plaque formation and composition in murine atherosclerosis and investigated its actions on macrophage responses to atherogenic stimuli in vitro. In atherosclerosis induced by high‐cholesterol diet, Apoe −/− mice treated with colchicine had 50% reduction in aortic oil Red O + plaque area compared to saline control ( p = .001) and lower oil Red O + staining of aortic sinus lesions ( p = .03). In vitro, addition of 10 nM colchicine inhibited foam cell formation from murine and human macrophages after treatment with oxidized LDL (ox‐LDL). Mechanistically, colchicine downregulated glycosylation and surface expression of the ox‐LDL uptake receptor, CD36, and reduced CD36 + staining in aortic sinus plaques. It also decreased macrophage uptake of cholesterol crystals, resulting in lower intracellular lysosomal activity, inhibition of the NLRP3 inflammasome, and reduced secretion of IL‐1β and IL‐18. Colchicine's anti‐atherosclerotic actions were accentuated in a mouse model of unstable plaque induced by carotid artery tandem stenosis surgery, where it decreased lesion size by 48% ( p = .01), reduced lipid ( p = .006) and necrotic core area ( p = .007), increased collagen content and cap‐to‐necrotic core ratio ( p = .05), and attenuated plaque neutrophil extracellular traps ( p .001). At low dose, colchicine's effects were not accompanied by the evidence of microtubule depolymerization. Together, these results show that colchicine exerts anti‐atherosclerotic and plaque‐stabilizing effects at low dose by inhibiting foam cell formation and cholesterol crystal‐induced inflammation. This provides a new framework to support its repurposing for atherosclerotic cardiovascular disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-07-2014
DOI: 10.1161/CIRCRESAHA.115.303299
Abstract: Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are erse, with evidence for local production and circulatory renewal. We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate. Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units. Aorta showed a unique predilection for generating macrophage colony-forming units. Aortic macrophage colony-forming unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially located, where they were the predominant source of proliferating cells in the aortic wall. Aortic Sca-1 + CD45 + cells were transcriptionally and phenotypically distinct from neighboring cells lacking stem cell antigen-1 or CD45 and contained a proliferative (Ki67 + ) Lin − c-Kit + CD135 − CD115 + CX 3 CR1 + Ly6C + CD11b − subpopulation, consistent with the immunophenotypic profile of macrophage progenitors. Adoptive transfer studies revealed that Sca-1 + CD45 + adventitial macrophage progenitor cells were not replenished via the circulation from bone marrow or spleen, nor was their prevalence diminished by depletion of monocytes or macrophages by liposomal clodronate treatment or genetic deficiency of macrophage colony-stimulating factor. Rather adventitial macrophage progenitor cells were upregulated in hyperlipidemic ApoE −/− and LDL-R −/− mice, with adventitial transfer experiments demonstrating their durable contribution to macrophage progeny particularly in the adventitia, and to a lesser extent the atheroma, of atherosclerotic carotid arteries. The discovery and characterization of resident vascular adventitial macrophage progenitor cells provides new insight into adventitial biology and its participation in atherosclerosis and provokes consideration of the broader existence of local macrophage progenitors in other tissues.
Publisher: Springer Science and Business Media LLC
Date: 13-05-2019
DOI: 10.1038/S41598-019-43765-8
Abstract: The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1 + CD45 + progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1 + CD45 + cells were localised to adventitia and lacked surface expression of endothelial markers ( % for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE −/− aortas. Although Sca-1 + CD45 + cells from C57BL/6 aorta did not express CD31, they formed CD31 + colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1 + CD45 + cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE −/− mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1 + CD45 + cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.
Publisher: AME Publishing Company
Date: 08-2016
Publisher: Springer Science and Business Media LLC
Date: 29-06-2011
DOI: 10.1007/S10554-010-9657-5
Abstract: Cardiac fibrosis plays an important prognostic role in nonischemic cardiomyopathy (NICM), making it a potential therapeutic target. Although electromechanical mapping has been used to identify myocardial scar and facilitate intramyocardial intervention in the setting of ischemic heart disease, its application has not been described in NICM. We assessed the detection of myocardial fibrosis by endoventricular electromechanical mapping in an experimental model of NICM. The NOGA® XP system was used to perform left ventricular mapping in twelve sheep that had undergone intracoronary doxorubicin dosing to induce NICM and in six healthy control animals. Results for endocardial voltage and mechanical shortening were evaluated against myocardial fibrosis burden, as determined by delayed-enhancement cardiac magnetic resonance and quantitative histomorphometry. Doxorubicin treatment resulted in dilated cardiomyopathy with moderate-severe impairment of left ventricular ejection fraction. Late gadolinium uptake was present in 9/12 doxorubicin animals, while histological fibrosis was approximately doubled compared to controls and was distributed multisegmentally throughout the left ventricle. Cardiomyopathy was associated with widespread reductions in unipolar and bipolar voltage litude and endocardial shortening. Each parameter showed an inverse relationship with the burden of fibrosis. Moreover, unipolar voltage and linear local shortening ratio displayed moderate accuracy for identifying myocardial segments with delayed contrast enhancement or increased fibrosis content, with optimal discriminatory thresholds of 7.5 mV and 11.5%, respectively. In this model of NICM, electromechanical mapping shows potential for delineating segmental differences in fibrosis. Pending clinical evaluation, it may therefore have applicability for directing targeted intramyocardial interventions in nonischemic heart disease.
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.HRTHM.2010.05.010
Abstract: Hypertension accounts for more atrial fibrillation (AF) than any other predisposing factor. The purpose of this study was to characterize the time course, extent, and electrostructural correlation of atrial remodeling in chronic hypertension. Thirty-two sheep were studied: 21 with induced "one-kidney, one-clip" hypertension and 11 controls. Sequential closed-chest electrophysiologic studies were performed in 12 conscious animals (6 hypertensive, 6 controls) to evaluate progressive remodeling over 15 weeks. Additional atrial structural/functional analyses were performed in 5 controls and at 5, 10, and 15 weeks of hypertension (five per time point) via histology/cardiac magnetic resonance imaging to correlate with open-chest electrophysiologic parameters. The hypertensive group developed a progressive increase in mean arterial pressure (P <.001). Mean effective refractory periods were uniformly higher at all time points (P <.001). Progressive biatrial hypertrophy (P = .003), left atrial dysfunction (P <.05) and greater AF inducibility were seen early with increased inflammation from 5 weeks of hypertension. In contrast, significant conduction slowing (P <.001) with increased heterogeneity (P <.001) along with increased interstitial fibrosis resulted in longer and more fractionated AF episodes only from 10 weeks of hypertension. Significant electrostructural correlation was seen in conduction abnormalities and AF inducibility with both atrial inflammation and fibrosis. Hypertension is associated with early and progressive changes in atrial remodeling. Atrial remodeling occurs at different time domains in chronic hypertension with significant electrostructural correlation of the remodeling cascade. Early institution of antihypertensive treatment may prevent formation of substrate capable of maintaining AF.
Publisher: Springer Science and Business Media LLC
Date: 09-11-2011
DOI: 10.1186/SCRT84
Publisher: Elsevier BV
Date: 08-2019
Publisher: Oxford University Press (OUP)
Date: 06-2023
Abstract: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. Anxiety, depression, and post-traumatic stress disorder (PTSD) are underappreciated symptoms. We aimed to systematically synthesize prevalence estimates of mood disorders and symptom severities, pre- and post-ICD insertions. Comparisons were made with control groups, as well as within ICD patients by indication (primary vs. secondary), sex, shock status, and over time. Databases (Medline, PsycINFO, PubMed, and Embase) were searched without limits from inception to 31 August 2022 4661 articles were identified, 109 (39 954 patients) of which met criteria. Random-effects meta-analyses revealed clinically relevant anxiety in 22.58% (95%CI 18.26–26.91%) of ICD patients across all timepoints following insertion and depression in 15.42% (95%CI 11.90–18.94%). Post-traumatic stress disorder was seen in 12.43% (95%CI 6.90–17.96%). Rates did not vary relative to indication group. Clinically relevant anxiety and depression were more likely in ICD patients who experienced shocks [anxiety odds ratio (OR) = 3.92 (95%CI 1.67–9.19) depression OR = 1.87 (95%CI 1.34–2.59)]. Higher symptoms of anxiety were seen in females than males post-insertion [Hedges’ g = 0.39 (95%CI 0.15–0.62)]. Depression symptoms decreased in the first 5 months post-insertion [Hedges’ g = 0.13 (95%CI 0.03–0.23)] and anxiety symptoms after 6 months [Hedges’ g = 0.07 (95%CI 0–0.14)]. Depression and anxiety are highly prevalent in ICD patients, especially in those who experience shocks. Of particular concern is the prevalence of PTSD following ICD implantation. Psychological assessment, monitoring, and therapy should be offered to ICD patients and their partners as part of routine care.
Publisher: Wiley
Date: 18-02-2016
DOI: 10.1002/CCD.25419
Abstract: Management of acute thrombotic occlusion of coronary artery aneurysms is challenging with a lack of randomized trial evidence. We report an unusual case of a 30-year-old Indian Australian male who presented with an extensive anterior STEMI because of very large thrombus burden in a dilated proximal left anterior descending artery. A relatively conservative treatment approach comprising emergency aspiration thrombectomy and ongoing infusion of glycoprotein IIb/IIIa inhibitor, guided by surveillant inpatient angiography and intravascular ultrasound, helped achieve a satisfactory outcome in a complex setting in which percutaneous coronary angioplasty and stenting were not desirable. © 2014 Wiley Periodicals, Inc.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2019
Publisher: AME Publishing Company
Date: 04-2017
Publisher: Elsevier BV
Date: 08-2019
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.STEM.2008.05.012
Abstract: In this issue of Cell Stem Cell, Belema-Bedada et al. (2008) describe a novel mechanism by which bone marrow-derived adult mesenchymal stem cells migrate to sites of damaged heart tissue. This process is dependent on the intracellular adaptor molecule FROUNT, which interacts with the chemokine receptor CCR2.
Publisher: Elsevier BV
Date: 08-2018
Publisher: Springer Science and Business Media LLC
Date: 30-11-2011
Publisher: Springer Science and Business Media LLC
Date: 19-04-2017
DOI: 10.1007/S40259-017-0220-Y
Abstract: The clinical reality of residual risk despite statin (HMG-CoA reductase inhibitor) therapy and emergence of statin intolerance support the need to develop additional lipid-lowering strategies. Proprotein convertase subtilisin kexin type 9 (PCSK9) has received considerable attention by virtue of genetic and clinical studies that have revealed its pivotal role in the regulation of cholesterol homeostasis. Monoclonal antibodies have been developed targeting PCSK9, which have been demonstrated to produce profound low-density lipoprotein cholesterol (LDL-C) lowering when provided as monotherapy or in combination with statins. With the reports that the PCSK9 inhibitor evolocumab has a favorable impact on both plaque progression and cardiovascular outcomes, these findings begin to translate the benefits of PCSK9 inhibition from lipids to the vessel wall and ultimately to clinical outcomes. The clinical implications for the use of these agents are reviewed in this article.
Publisher: Wiley
Date: 26-09-2011
Publisher: S. Karger AG
Date: 2006
DOI: 10.1159/000091415
Publisher: Springer Science and Business Media LLC
Date: 03-09-2016
DOI: 10.1007/S10554-015-0762-3
Abstract: Epicardial fat volume (EFV) has been suggested to promote atherosclerotic plaque development in coronary arteries, and has been correlated with both coronary stenosis and acute coronary events. Although associated with progression of coronary calcification burden, a relationship with progression of coronary atheroma volume has not been previously tested. We studied patients who had clinically indicated serial 320-row multi-detector computer tomography coronary angiography with a median 25-month interval. EFV was measured at baseline and follow-up. In vessels with coronary stenosis, quantitative analysis was performed to measure atherosclerotic plaque burden, volume and aggregate plaque volume at baseline and follow-up. The study comprised 64 patients (58.4 ± 12.2 years, 27 males, 192 vessels, 193 coronary segments). 79 (41 %) coronary segments had stenosis at baseline. Stenotic segments were associated with greater baseline EFV than those without coronary stenosis (117.4 ± 45.1 vs. 102.3 ± 51.6 cm(3), P = 0.046). 46 (24 %) coronary segments displayed either new plaque formation or progression of adjusted plaque burden at follow-up. These were associated with higher baseline EFV than segments without stenosis or those segments that had stenoses that did not progress (128.7 vs. 101.0 vs. 106.7 cm(3) respectively, P = 0.006). On multivariate analysis, baseline EFV was the only independent predictor of coronary atherosclerotic plaque progression or new development (P = 0.014). High baseline EFV is associated with the presence of coronary artery stenosis and plaque volume progression. Accumulation of EFV may be implicated in the evolution and progression of coronary atheroma.
Publisher: Mary Ann Liebert Inc
Date: 07-2018
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.HLC.2019.01.011
Abstract: Bifurcation percutaneous coronary intervention (PCI) remains a challenging frontier in interventional cardiology, especially in the setting of ST-elevation myocardial infarction (STEMI). We examined the procedural and clinical outcomes of this patient subset. We conducted a retrospective case-control study. Between February 2006 and March 2011, 129 patients with STEMI underwent bifurcation PCI at our institution. One hundred and twenty-nine (129) control STEMI patients with non-bifurcation PCI were selected from the institutional database, matched for age, gender, culprit vessel, and lesion location. Patients with cardiac arrest, cardiogenic shock, or who required mechanical ventilation were excluded. Twelve (12)-month follow-up data were collected by telephone calls and examination of the medical records. The average age of patients presenting with STEMI was 61.6 ± 13.1 in the bifurcation group and 61.5 + 31.1 in the non-bifurcation group. There was no difference in lesion type, use of thrombus aspiration catheters, or glycoprotein inhibitors (GPI) among them. Also, the use of drug eluting stent (DES), total cumulative length of stent used, and diameter of the post-dilation balloon were similar. Final kissing balloon post-dilation was performed in 40.3% of bifurcation PCI cases. The incidence of procedural failure (TIMI 0 flow) was 1.5% vs. 0% p = 0.478. At 12-months follow-up, the bifurcation PCI group had higher incidence of target lesion revascularisation (TLR) (10.9% vs. 3.9%, p = 0.050), mortality (10.1% vs. 2.3%, p = 0.020), and stent thrombosis (9.3% vs. 1.6% p = 0.013) comprising one acute, nine subacute, and two late vs. two subacute stent thromboses. During acute STEMI, bifurcation PCI has excellent acute procedural outcomes, but significantly increased incidence of TLR, stent thrombosis and mortality at 12 months.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2018
DOI: 10.1161/ATVBAHA.118.307026
Abstract: Considerable evidence from preclinical and population studies suggests that HDLs (high-density lipoproteins) possess atheroprotective properties. Reports from HDL infusion studies in animals and early clinical imaging trials reported evidence of plaque regression. These findings have stimulated further interest in developing new agents targeting HDL. However, the results of more recent imaging studies in the setting of high-intensity statin use have been disappointing. As the concept of plaque changes with HDL therapeutics evolves and imaging technology to evaluate these effects advances, there will become increasing opportunity to determine the effects of HDL agents on atherosclerotic plaque (Graphic Abstract).
Publisher: Elsevier BV
Date: 10-2008
Publisher: Wiley
Date: 15-01-2022
Publisher: Springer Science and Business Media LLC
Date: 23-10-2009
DOI: 10.1007/S12265-009-9138-1
Abstract: Method for delivery remains a central component of stem cell-based cardiovascular research. Comparative studies have demonstrated the advantages of administering cell therapy directly into the myocardium, as distinct from infusing cells into the systemic or coronary vasculature. Intramyocardial delivery can be achieved either transepicardially or transendocardially. The latter involves percutaneous, femoral arterial access and the retrograde passage of specially designed injection catheters into the left ventricle, making it less invasive and more relevant to wider clinical practice. Imaging-based navigation plays an important role in guiding catheter manipulation and directing endomyocardial injections. The most established strategy for three-dimensional, intracardiac navigation is currently endoventricular, electromechanical mapping, which offers superior spatial orientation compared to simple x-ray fluoroscopy. Its provision of point-by-point, electrophysiologic and motion data also allows characterization of regional myocardial viability, perfusion, and function, especially in the setting of ischemic heart disease. Integrating the mapping catheter with an injection port enables this diagnostic information to facilitate the targeting of intramyocardial stem cell delivery. This review discusses the diagnostic accuracy and expanding therapeutic application of electromechanical navigation in cell-based research and describes exciting developments which will improve the technology's sensing capabilities, image registration, and delivery precision in the near future.
Publisher: MDPI AG
Date: 21-05-2020
DOI: 10.3390/IJMS21103633
Abstract: Diabetes mellitus affects millions of people worldwide and is associated with devastating vascular complications. A number of these complications, such as impaired wound healing and poor coronary collateral circulation, are characterised by impaired ischaemia-driven angiogenesis. There is increasing evidence that high-density lipoproteins (HDL) can rescue diabetes-impaired angiogenesis through a number of mechanisms, including the modulation of endothelial cell metabolic reprogramming. Endothelial cell metabolic reprogramming in response to tissue ischaemia is a driver of angiogenesis and is dysregulated by diabetes. Specifically, diabetes impairs pathways that allow endothelial cells to upregulate glycolysis in response to hypoxia adequately and impairs suppression of mitochondrial respiration. HDL rescues the impairment of the central hypoxia signalling pathway, which regulates these metabolic changes, and this may underpin several of its known pro-angiogenic effects. This review discusses the current understanding of endothelial cell metabolism and how diabetes leads to its dysregulation whilst examining the various positive effects of HDL on endothelial cell function.
Publisher: Oxford University Press (OUP)
Date: 20-09-2019
Publisher: Springer Science and Business Media LLC
Date: 30-07-2014
DOI: 10.1007/S11886-014-0526-Z
Abstract: Well into the second decade since its conception, cell transplantation continues to undergo intensive evaluation for the treatment of myocardial infarction. At a mechanistic level, its objectives remain to replace lost cardiac cell mass with new functioning cardiomyocytes and vascular cells, thereby minimizing infarct size and scar formation, and improving clinical outcomes by preventing adverse left ventricular remodeling and recurrent ischemic events. Many different cell types, including pluripotent stem cells and various adult-derived progenitor cells, have been shown to have therapeutic potential in preclinical studies, while early phase human trial experience has provided ergent outcomes and fundamental lessons, emphasizing that there remain key issues to address and challenges to overcome before cell therapy can be applied to wider clinical practice. The purpose of this review is to provide a balanced update on recent seminal developments in this exciting field and look to the next important steps to ensure its forward progression.
Publisher: Wiley
Date: 21-02-2013
DOI: 10.1002/CCD.24733
Abstract: The purpose of this study was to evaluate the left main (LM) coronary artery anatomy using three-dimensional (3D) quantitative coronary angiography (QCA) software as compared to intravascular ultrasound (IVUS). Percutaneous intervention of the LM coronary artery is becoming more common in selected patients with LM coronary artery disease (CAD). Quantification of LM CAD by conventional angiography can be difficult. IVUS is considered the gold standard to evaluate LM anatomy and severity of CAD but entails additional steps, catheters, and expertise. Our objective was to compare a novel quantitative angiographic analysis system with IVUS for LM anatomy. Fifty five patients underwent both coronary angiography and IVUS of the LM. LM measurements were analyzed with 3D QCA (IC-PRO, Paieon, Israel) software using IVUS as the reference standard. The measurements included proximal, middle, distal minimal luminal diameter (MLD) and area. Additionally, lesion MLD, minimal luminal area were recorded by both systems. Bland-Altman plots were used to investigate agreement between the two imaging systems. Of the 55 patients in our cohort, average age was 66 ± 11 years (25% female). By Bland-Altman analysis there was very good agreement between 3D QCA and IVUS for measures of MLD and minimal lumen area (MLA). However, there was poor concordance in the estimation of plaque burden between the two methods. Our data demonstrate that 3D QCA software has fair agreement when compared with IVUS for imaging of LM MLD and MLA. These results suggest that 3D QCA could potentially be helpful to guide intervention of the LM.
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1016/J.CARDFAIL.2008.06.449
Abstract: There is a paucity of published experience investigating novel treatment strategies in preclinical and clinical studies of nonischemic cardiomyopathy. We set out to validate an ovine model of doxorubicin-induced cardiomyopathy, using cardiac magnetic resonance (CMR) to assess cardiac function. Ten Merino sheep (51 +/- 8 kg) underwent intracoronary infusions of doxorubicin (1 mg/kg dose) every 2 weeks. Cardiac magnetic resonance was performed at baseline and at 6 weeks after final doxorubicin dose, along with transthoracic echocardiography, measurement of right heart pressure, and cardiac output. After final CMR examination, heart specimens were harvested for histologic analysis. The total dose of doxorubicin administered per animal was 3.8 +/- 0.5 mg/kg. Two animals died prematurely during the study protocol, with evidence of myocarditis. In the remaining 8 sheep, left ventricular ejection fraction dropped from 46.2 +/- 4.7% to 31.3 +/- 8.5% (P < .001), accompanied by reductions in fractional shortening (31.6 +/- 1.8% baseline versus 18.2 +/- 3.9% final, P < .01), cardiac output (3.8 +/- 0.6 L/min versus 3.0 +/- 0.4 L/min, P < .05) and right ventricular ejection fraction (39.5 +/- 5.6% versus 28.9 +/- 9.6%, P < .05). However, significant end-diastolic dilatation of the left ventricle was not observed. Delayed gadolinium uptake was detected by CMR in 2 sheep, in a typical nonischemic pattern. Widespread, multifocal histologic abnormalities consisted of cardiomyocyte degeneration, vasculopathy, inflammatory infiltrates, and replacement fibrosis. Moderate-severe cardiac dysfunction was reproducibly achieved through high-dose intracoronary doxorubicin, with acceptable animal mortality. CMR provides a powerful tool for assessing myocardial function, structural remodeling, and viability in such models.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2017
Publisher: S. Karger AG
Date: 2013
DOI: 10.1159/000354236
Abstract: b i Objective: /i /b Polycystic kidney disease (PKD), a monogenic disease with an autosomal dominant or an autosomal recessive form of inheritance (ARPKD), is the most common genetic cause of renal dysfunction and end-stage renal failure. In addition to the development of cysts, the autosomal form of PKD is associated with vascular endothelial dysfunction, a marker of vascular disease. Whether vascular endothelial dysfunction is also present in ARPKD, and its relationship with renal dysfunction remain to be determined. b i Methods: /i /b ARPKD rats (PCK model) and controls were studied at 6 and 10 weeks of age, and mean arterial pressure and renal function were measured. Aortic endothelial function was assessed using organ chamber techniques. Aortic endothelial cells (ECs) were isolated, characterized and their function studied. b i Results: /i /b Compared to controls, ARPKD animals had a decrease in the vasorelaxation to endothelium-dependent vasodilators, even prior to changes in mean arterial pressure or renal function. The abnormal vasoreactivity was corrected with smlcap L /smlcap -arginine (a precursor of nitric oxide, NO), while the expression of endothelial NO synthase (eNOS) was unchanged. Furthermore, isolated ECs from 6-week-old ARPKD animals showed increased oxidative stress, with preserved eNOS expression and abnormal patterns of migration and angiogenic capacity (measured by the scratch and tube formation assays, respectively). b i Conclusion: /i /b ARPKD leads to impairments in aortic vascular function and ECs at an early stage, which can have significant functional consequences, potentially representing a novel therapeutic target in this disease.
Publisher: Springer Science and Business Media LLC
Date: 13-12-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-11-2022
DOI: 10.1161/CIRCULATIONAHA.122.060308
Abstract: Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for s le size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.
Publisher: American Society of Hematology
Date: 30-06-2023
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.HRTHM.2009.11.031
Abstract: Hypertension is frequently complicated by the development of atrial fibrillation (AF). However, the mechanisms of this link remain poorly understood. In addition, whether short-term hypertension can result in a substrate for AF is not known. The purpose of this study was to characterize the atrial substrate predisposing to AF due to short-duration hypertension. Sixteen sheep were studied: 10 had induced hypertension for 7 +/- 4 weeks via the "one-kidney, one-clip" model, and six were controls. Cardiac magnetic resonance imaging was used to assess functional changes. Open-chest electrophysiological study was performed using a custom-made 128-electrode epicardial plaque applied to both right (RA) and left atria (LA), including the Bachmann's bundle, to determine effective refractory periods (ERPs) and conduction velocity at four pacing cycle lengths from six sites. Tissue specimens were harvested for structural analysis. The hypertensive group demonstrated the following compared with controls: higher blood pressure (P <.0001), enlarged LA (P <.05), reduced LA ejection fraction (P <.05), uniformly higher mean ERP (P <.001), slower mean conduction velocity (P <.001), higher conduction heterogeneity index (P <.0001), greater AF inducibility (P = .03), and increased AF durations (P = .04). Picrosirius red staining of atrial tissues revealed increased interstitial fibrosis (P <.0001). There was also evidence of increased inflammatory cell infiltrates (P <.0001). Short-duration hypertension is associated with significant atrial remodeling characterized by atrial enlargement/dysfunction, interstitial fibrosis, inflammation, slowed/heterogeneous conduction, increased ERP, and greater propensity for AF.
Publisher: Czech Society of Cardiology
Date: 11-08-2019
Publisher: Royal College of Physicians
Date: 06-2016
Publisher: Springer Science and Business Media LLC
Date: 05-05-2009
Abstract: Pericardial adipose tissue (PAT) has been shown to be an independent predictor of coronary artery disease. To date its assessment has been restricted to the use of surrogate echocardiographic indices such as measurement of epicardial fat thickness over the right ventricular free wall, which have limitations. Cardiovascular magnetic resonance (CMR) offers the potential to non-invasively assess total PAT, however like other imaging modalities, CMR has not yet been validated for this purpose. Thus, we sought to describe a novel technique for assessing total PAT with validation in an ovine model. 11 merino sheep were studied. A standard clinical series of ventricular short axis CMR images (1.5T Siemens Sonata) were obtained during mechanical ventilation breath-holds. Beginning at the mitral annulus, consecutive end-diastolic ventricular images were used to determine the area and volume of epicardial, paracardial and pericardial adipose tissue. In addition adipose thickness was measured at the right ventricular free wall. Following euthanasia, the paracardial adipose tissue was removed from the ventricle and weighed to allow comparison with corresponding CMR measurements. There was a strong correlation between CMR-derived paracardial adipose tissue volume and ex vivo paracardial mass (R 2 = 0.89, p 0.001). In contrast, CMR measurements of corresponding RV free wall paracardial adipose thickness did not correlate with ex vivo paracardial mass (R 2 = 0.003, p = 0.878). In this ovine model, CMR-derived paracardial adipose tissue volume, but not the corresponding and conventional measure of paracardial adipose thickness over the RV free wall, accurately reflected paracardial adipose tissue mass. This study validates for the first time, the use of clinically utilised CMR sequences for the accurate and reproducible assessment of pericardial adiposity. Furthermore this non-invasive modality does not use ionising radiation and therefore is ideally suited for future studies of PAT and its role in cardiovascular risk prediction and disease in clinical practice.
Publisher: BMJ
Date: 02-2020
DOI: 10.1136/BMJOPEN-2019-034551
Abstract: Coronary artery bypass grafting (CABG) surgery is known to improve vascular function and cardiac-related mortality rates however, it is associated with high rates of postoperative cognitive decline and delirium. Previous attempts to prevent post-CABG cognitive decline using pharmacological and surgical approaches have been largely unsuccessful. Cognitive prehabilitation and rehabilitation are a viable yet untested option for CABG patients. We aim to investigate the effects of preoperative cognitive training on delirium incidence, and preoperative and postoperative cognitive training on cognitive decline at 4 months post-CABG. This study is a randomised, single-blinded, controlled trial investigating the use of computerised cognitive training (CCT) both pre-CABG and post-CABG (intervention group) compared with usual care (control group) in older adults undergoing CABG in Adelaide, South Australia. Those in the intervention group will complete 1–2 weeks of CCT preoperatively (45–60 min sessions, 3.5 sessions/week) and 12 weeks of CCT postoperatively (commencing 1 month following surgery, 45–60 min sessions, 3 sessions/week). All participants will undergo cognitive testing preoperatively, over their hospital stay including delirium, and postoperatively for up to 1 year. The primary delirium outcome variable will be delirium incidence (presence vs absence) the primary cognitive decline variable will be at 4 months (significant decline vs no significant decline/improvement from baseline). Logistic regression modelling will be used, with age and gender as covariates. Secondary outcomes include cognitive decline from baseline to discharge, and at 6 months and 1 year post-CABG. Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee (South Australia, Australia) and the University of South Australia Human Ethics Committee, with original approval obtained on 13 December 2017. It is anticipated that approximately two to four publications and multiple conference presentations (national and international) will result from this research. This clinical trial is registered with the Australian New Zealand Clinical Trials Registry and relates to the pre-results stage. Registration number: ACTRN12618000799257.
Publisher: SAGE Publications
Date: 08-07-2013
Abstract: In vivo assessment of ventricular function in rodents has largely been restricted to transthoracic echocardiography (TTE). However 1.5 T cardiac magnetic resonance (CMR) and transoesophageal echocardiography (TOE) have emerged as possible alternatives. Yet, to date, no study has systematically assessed these three imaging modalities in determining ejection fraction (EF) in rats. Twenty rats underwent imaging four weeks after surgically-induced myocardial infarction. CMR was performed on a 1.5 T scanner, TTE was conducted using a 9.2 MHz transducer and TOE was performed with a 10 MHz intracardiac echo catheter. Correlation between the three techniques for EF determination and analysis reproducibility was assessed. Moderate-strong correlation was observed between the three modalities the greatest between CMR and TOE (intraclass correlation coefficient (ICC) = 0.89), followed by TOE and TTE (ICC = 0.70) and CMR and TTE (ICC = 0.63). Intra- and inter-observer variations were excellent with CMR (ICC = 0.99 and 0.98 respectively), very good with TTE (0.90 and 0.89) and TOE (0.87 and 0.84). Each modality is a viable option for evaluating ventricular function in rats, however the high image quality and excellent reproducibility of CMR offers distinct advantages even at 1.5 T with conventional coils and software.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2012
Publisher: European Delirium Association
Date: 21-02-2023
DOI: 10.56392/001C.67976
Abstract: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45–60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45–60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke’s Cognitive Examination III and CANTAB z-scored). Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the s le size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective.
Publisher: American Medical Association (AMA)
Date: 09-2018
Publisher: SAGE Publications
Date: 09-2015
Abstract: Polycystic kidney disease (PKD) is a common cause of end-stage renal failure, for which there is no accepted treatment. Progenitor and stem cells have been shown to restore renal function in a model of renovascular disease, a disease that shares many features with PKD. The objective of this study was to examine the potential of adult stem cells to restore renal structure and function in PKD. Bone marrow-derived mesenchymal stromal cells (MSCs, 2.5 × 10 5 ) were intrarenally infused in 6-week-old PCK rats. At 10 weeks of age, PCK rats had an increase in systolic blood pressure (SBP) versus controls (126.22 ± 2.74 vs. 116.45 ± 3.53 mmHg, p 0.05) and decreased creatinine clearance (3.76 ± 0.31 vs. 6.10 ± 0.48 μl/min/g, p 0.01), which were improved in PKD animals that received MSCs (SBP: 114.67 ± 1.34 mmHg, and creatinine clearance: 4.82 ± 0.24 μl/min/g, p = 0.001 and p = 0.003 vs. PKD, respectively). MSCs preserved vascular density and glomeruli diameter, measured using microcomputed tomography. PCK animals had increased urine osmolality (843.9 ± 54.95 vs. 605.6 ± 45.34 mOsm, p 0.01 vs. control), which was improved after MSC infusion and not different from control (723.75 ± 56.6 mOsm, p = 0.13 vs. control). Furthermore, MSCs reduced fibrosis and preserved the expression of proangiogenic molecules, while cyst size and number were unaltered by MSCs. Delivery of exogenous MSCs improved vascular density and renal function in PCK animals, and the benefit was observed up to 4 weeks after a single infusion. Cell-based therapy constitutes a novel approach in PKD.
Publisher: Japan Atherosclerosis Society
Date: 2017
DOI: 10.5551/JAT.RV16009
Publisher: Springer Science and Business Media LLC
Date: 12-04-2014
DOI: 10.1007/S00330-014-3137-6
Abstract: We evaluate whether circumferential strain derived from grid-tagged CMR is a better method for assessing improvement in segmental contractile function after STEMI compared to late gadolinium enhancement (LGE). STEMI patients post primary PCI underwent baseline CMR (day 3) and follow-up (day 90). Cine, grid-tagged and LGE images were acquired. Baseline LGE infarct hyperenhancement was categorised as ≤25 %, 26-50 %, 51-75 % and >75 % hyperenhancement. The segmental baseline circumferential strain (CS) and circumferential strain rate (CSR) were calculated from grid-tagged images. Segments demonstrating an improvement in wall motion of ≥1 grade compared to baseline were regarded as having improved segmental contractile-function. Forty-five patients (aged 58 ± 12 years) and 179 infarct segments were analysed. A baseline CS cutoff of -5 % had sensitivity of 89 % and specificity of 70 % for detection of improvement in segmental-contractile-function. On receiver-operating characteristic analysis for predicting improvement in contractile function, AUC for baseline CS (0.82) compared favourably to LGE hyperenhancement (0.68), MVO (0.67) and baseline-CSR (0.74). On comparison of AUCs, baseline CS was superior to LGE hyperenhancement and MVO in predicting improvement in contractile function (P < 0.001). On multivariate-analysis, baseline CS was the independent predictor of improvement in segmental contractile function (P < 0.001). Grid-tagged CMR-derived baseline CS is a superior predictor of improvement in segmental contractile function, providing incremental value when added to LGE hyperenhancement and MVO following STEMI. Baseline CS predicts contractile function recovery better than LGE and MVO following STEMI. Baseline CS predicts contractile function recovery better than baseline CSR following STEMI. Baseline CS provides incremental value to LGE and MVO following STEMI.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.ATHEROSCLEROSIS.2018.04.022
Abstract: Wall shear stress (WSS) has an important role in the natural history of coronary atherosclerosis. The aim of this study is to investigate the relationship between WSS and the lipid content of atherosclerotic plaques as assessed by near-infrared spectroscopy (NIRS). We performed serial NIRS and intravascular ultrasound (IVUS) upon Doppler coronary flow guidewire of coronary plaques at baseline and after 12-18 months in 28 patients with <30% angiographic stenosis, who presented with coronary artery disease. Segmental WSS, plaque burden and NIRS-derived lipid rich plaque (LRP) were evaluated at both time-points in 482 consecutive 2-mm coronary segments. Segments with LRP at baseline (n = 106) had a higher average WSS (1.4 ± 0.6 N/m Coronary segments with high WSS associate with progression of lipid content over time, which may indicate transformation to a more vulnerable phenotype.
Publisher: Wiley
Date: 19-07-2011
DOI: 10.1111/J.1540-8167.2010.01851.X
Abstract: All preclinical studies of atrial remodeling in heart failure (HF) have been confined to a single model of rapid ventricular pacing. To evaluate whether the atrial changes were specific to the model or represented an end result of HF, this study aimed to characterize atrial remodeling in an ovine model of doxorubicin-induced cardiomyopathy. Fourteen sheep, 7 with cardiomyopathy induced by repeated intracoronary doxorubicin infusions and 7 controls, were studied. The development of HF was monitored by cardiac imaging and hemodynamic parameters. Open chest electrophysiological study was performed using custom-made 128-electrode epicardial plaque assessing effective refractory period (ERP) and conduction velocity. Atrial tissues were harvested for structural analysis. The HF group had demonstrable moderate global HF (left ventricular ejection fraction [LVEF]: 37.1 vs 46.4% P = 0.003) and showed the following compared to controls: left atrial dilatation (P = 0.02) and dysfunction (P = 0.005) longer P-wave duration (P < 0.05) higher ERP at all cycle lengths (P ≤ 0.002) and locations (P < 0.001) slower conduction velocity (P < 0.001) increased conduction heterogeneity index (P < 0.001) increased atrial fibrosis (right atrial [RA]: 5.9 ± 2.6 vs 2.8 ± 0.9% P < 0.0001, left atrial [LA]: 3.7 ± 2.2 vs 2.4 ± 1.1% P = 0.002), and longer induced atrial fibrillation (AF) episodes (16 ± 22 vs 2 ± 3 seconds P = 0.04). In this model of HF, there was significant atrial remodeling characterized by atrial enlargement/dysfunction, increased fibrosis, slowed/heterogeneous conduction, and increased refractoriness associated with more sustained AF. These findings appear the "same sort" to previous models of HF implicating a final common substrate leading to the development of AF in HF.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2015
DOI: 10.1161/CIRCINTERVENTIONS.114.002121
Abstract: Current risk models for predicting long-term mortality after percutaneous coronary intervention are restricted to all-cause mortality. We sought to develop novel risk models for the prediction of cardiac and noncardiac mortality after percutaneous coronary intervention. We retrospectively evaluated patients who underwent index percutaneous coronary intervention at Mayo Clinic from 2003 to 2008. Long-term deaths were ascertained through scheduled prospective surveillance. Cause of death was determined via telephone interviews, medical records, and autopsy reports. Fine and Gray extension of Cox proportional hazards models was used to model cause-specific cumulative incidence. Candidate variables and interactions were chosen a priori, without variable selection methods. Resulting models were mapped to an integer-based risk score. The study comprised 6636 patients followed up over a median of 62 months (25th, 75th percentiles: 45, 77 months). There were 1488 deaths, 518 (35%) cardiac, 938 (63%) noncardiac, and 32 (2%) unknown. The 5-year predicted cardiac mortality ranged from 0.6% to 97%, with a corrected c -statistic of 0.82. Risk factors for cardiac death included age, body mass index, ejection fraction, and history of congestive heart failure. The integer score for noncardiac death included age, medicine index, body mass index, current smoker, noncardiac Charlson index and cardiac Charlson index, and accommodated significant age-based interactions for smoking and the 2 Charlson indices. Predicted noncardiac mortality at 5 years ranged from 0.2% to 81%, with a corrected c -statistic of 0.77. We report novel risk models to predict cardiac and noncardiac long-term mortality after percutaneous coronary intervention.
Publisher: Elsevier BV
Date: 03-2016
Publisher: Informa UK Limited
Date: 2010
DOI: 10.3109/08037050903576767
Abstract: The aim of this study is to characterize cardiac remodeling in a large animal model of hypertension. 23 sheep were subjected to unilateral nephrectomy followed by cl ing of the remaining renal artery to 60% ("one kidney-one clip", 1K1C) 3 weeks later. Blood pressure (BP) was monitored invasively over 73+/-28 days. Cardiac function was assessed with magnetic resonance imaging and compared with 12 size-matched controls. Detailed atrial histopathological analysis was performed. In the 1K1C animals, BP rose from baseline to reach a plateau by 4 weeks (systolic BP: 107+/-12 to 169+/-27, diastolic BP: 71+/-10 to 118+/-29 mmHg, both p< 0.0001) cardiac hypertrophy was significant when compared with controls with increased left ventricular weight [left ventricular (LV)/body wt: 2.7+/-0.5 vs 2.1+/-0.2 g/kg, p=0.01] as well as bi-atrial enlargement (right atrial, RA: 22.9+/-4.9 vs 15.7+/-2.8g, p=0.003 left atrial, LA: 35.5+/-6.7 vs 20.9+/-4.1g, p=0.0003) cardiac magnetic imaging demonstrated significantly increased LA volumes (end-diastolic volume: 42.9+/-6.8 vs 28.7+/-6.3 ml, p< 0.0001) and reduced LA ejection fraction (24.1+/-3.6 vs 31.6+/-3.0%, p=0.001) while LV function was relatively preserved (42.3+/-4.7 vs 46.4+/-4.1%, p=0.1) degeneration and necrosis of atrial myocytes were evident with increased atrial lymphocytic infiltration and interstitial fibrosis. The ovine 1K1C model produces reliable and reproducible hypertension with demonstrable cardiac end-organ damage.
Publisher: Wiley
Date: 19-10-2021
DOI: 10.1002/MED.21736
Abstract: Nitric oxide (NO) is a ubiquitous, volatile, cellular signaling molecule that operates across a wide physiological concentration range (pM–µM) in different tissues. It is a highly diffusible messenger and intermediate in various metabolic pathways. NO plays a pivotal role in maintaining optimum cardiovascular function, particularly by regulating vascular tone and blood flow. This review highlights the need for accurate, real‐time bioimaging of NO in clinical diagnostic, therapeutic, monitoring, and theranostic applications within the cardiovascular system. We summarize electrochemical, optical, and nanoscale sensors that allow measurement and imaging of NO, both directly and indirectly via surrogate measurements. The physical properties of NO render it difficult to accurately measure in tissues using direct methods. There are also significant limitations associated with the NO metabolites used as surrogates to indirectly estimate NO levels. All these factors added to significant variability in the measurement of NO using available methodology have led to a lack of sensors and imaging techniques of clinical applicability in relevant vascular pathologies such as atherosclerosis and ischemic heart disease. Challenges in applying current methods to biomedical and clinical translational research, including the wide physiological range of NO and limitations due to the characteristics and toxicity of the sensors are discussed, as are potential targets and modifications for future studies. The development of biocompatible nanoscale sensors for use in combination with existing clinical imaging modalities provides a feasible opportunity for bioimaging NO within the cardiovascular system.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-04-2015
DOI: 10.1161/CIRCRESAHA.116.305368
Abstract: The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease.
Publisher: Elsevier BV
Date: 03-2023
Publisher: Springer Science and Business Media LLC
Date: 29-09-2017
Publisher: Public Library of Science (PLoS)
Date: 13-09-2012
Publisher: AME Publishing Company
Date: 10-2020
DOI: 10.21037/CDT-20-1
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.MAYOCP.2016.05.008
Abstract: To assess early and late outcomes, including bleeding, in patients with thrombocytopenia undergoing percutaneous coronary intervention (PCI). We performed a retrospective single-center study of patients with preprocedural thrombocytopenia (platelet count ≤100,000/μL n=204) undergoing PCI between 2003 and 2015. Inhospital and late outcomes were compared with those of a matched control group without thrombocytopenia (n=1281). The most common causes of thrombocytopenia were liver disease, immune-mediated disease, and hematologic malignant neoplasms. Inhospital bleeding events after PCI were similar in patients with thrombocytopenia and matched controls (24 of 146 [16.4%] vs 179 of 1281 [14.0%] P=.40) and were largely classified as minor using the Bleeding Academic Research Consortium (BARC) classification (89% BARC 1 or 2). There was no significant difference in inhospital death (4 of 146 [2.7%] vs 71 of 1281 [2.0%] P=.56), but patients with thrombocytopenia had higher rates of platelet and red blood cell transfusion (18 of 146 [12.3%] vs 93 of 1281 [7.2%] P=.05). During long-term follow-up, Kaplan-Meier estimated rates of bleeding events (BARC ≥2) were higher for thrombocytopenia (at 5 years, 7.9% vs 3.6% P=.03). Patients with thrombocytopenia had a similar risk of long-term cardiac mortality, but significantly higher rates of noncardiac mortality (at 5 years, 28% vs 21% P=.02). This study suggests that short-term outcomes after PCI in patients with thrombocytopenia were favorable. On long-term follow-up, thrombocytopenia was associated with a higher risk of long-term noncardiac mortality and bleeding.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-01-2012
DOI: 10.1161/CIRCULATIONAHA.111.059360
Abstract: Hematopoiesis originates from the dorsal aorta during embryogenesis. Although adult blood vessels harbor progenitor populations for endothelial and smooth muscle cells, it is not known if they contain hematopoietic progenitor or stem cells. Here, we hypothesized that the arterial wall is a source of hematopoietic progenitor and stem cells in postnatal life. Single-cell aortic disaggregates were prepared from adult chow-fed C57BL/6 and apolipoprotein E–null (ApoE −/− ) mice. In short- and long-term methylcellulose-based culture, aortic cells generated a broad spectrum of multipotent and lineage-specific hematopoietic colony-forming units, with a preponderance of macrophage colony-forming units. This clonogenicity was higher in lesion-free ApoE −/− mice and localized primarily to stem cell antigen-1–positive cells in the adventitia. Expression of stem cell antigen-1 in the aorta colocalized with canonical hematopoietic stem cell markers, as well as CD45 and mature leukocyte antigens. Adoptive transfer of labeled aortic cells from green fluorescent protein transgenic donors to irradiated C57BL/6 recipients confirmed the content of rare hematopoietic stem cells (1 per 4 000 000 cells) capable of self-renewal and durable, low-level reconstitution of leukocytes. Moreover, the predominance of long-term macrophage precursors was evident by late recovery of green fluorescent protein–positive colonies from recipient bone marrow and spleen that were exclusively macrophage colony-forming units. Although trafficking from bone marrow was shown to replenish some of the hematopoietic potential of the aorta after irradiation, the majority of macrophage precursors appeared to arise locally, suggesting long-term residence in the vessel wall. The postnatal murine aorta contains rare multipotent hematopoietic progenitor/stem cells and is selectively enriched with stem cell antigen-1–positive monocyte/macrophage precursors. These populations may represent novel, local vascular sources of inflammatory cells.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-08-2022
Abstract: A significant proportion of patients with ST‐segment–elevation myocardial infarction (MI) have no standard modifiable cardiovascular risk factors (SMuRFs) and have unexpected worse 30‐day outcomes compared with those with SMuRFs. The aim of this article is to examine outcomes of patients with non–ST‐segment–elevation MI in the absence of SMuRFs. Presenting features, management, and outcomes of patients with non–ST‐segment–elevation MI without SmuRFs (hypertension, diabetes, hypercholesterolemia, smoking) were compared with those with SmuRFs in the Swedish MI registry SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies 2005–2018). Cox proportional hazard models were used. Out of 99 718 patients with non–ST‐segment–elevation MI, 11 131 (11.2%) had no SMuRFs. Patients without SMuRFs had higher all‐cause and cardiovascular mortality at 30 days (hazard ratio [HR], 1.20 [95% CI, 1.10–1.30], P .0001 and HR, 1.25 [95% CI, 1.13–1.38]), a difference that remained after adjustment for age and sex. SMuRF‐less patients were less likely to receive secondary prevention statins (76% versus 82%) angiotensin‐converting enzyme inhibitors/angiotensin receptor blockade (54% versus 72%) or β‐blockers (81% versus 87%, P for all .0001), with lowest rates observed in women without SMuRFs. In patients who survived to 30 days, rates of all‐cause and cardiovascular death were lower in patients without SMuRFs compared with those with risk factors, over 12 years. One in 10 patients presenting with non–ST‐segment–elevation MI present without traditional risk factors. The excess 30‐day mortality rate in this group emphasizes the need for both improved population‐based strategies for prevention of MI, as well as the need for equitable evidence‐based treatment at the time of an MI.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Springer Science and Business Media LLC
Date: 21-11-2017
DOI: 10.1038/S41598-017-15772-0
Abstract: Organic fluorescent probes are widely used to detect key biomolecules however, they often lack the photostability required for extended intracellular imaging. Here we report a new hybrid nanomaterial (peroxynanosensor, PNS), consisting of an organic fluorescent probe bound to a nanodiamond, that overcomes this limitation to allow concurrent and extended cell-based imaging of the nanodiamond and ratiometric detection of hydrogen peroxide. Far-red fluorescence of the nanodiamond offers continuous monitoring without photobleaching, while the green fluorescence of the organic fluorescent probe attached to the nanodiamond surface detects hydrogen peroxide on demand. PNS detects basal production of hydrogen peroxide within M1 polarised macrophages and does not affect macrophage growth during prolonged co-incubation. This nanosensor can be used for extended bio-imaging not previously possible with an organic fluorescent probe, and is spectrally compatible with both Hoechst 33342 and MitoTracker Orange stains for hyperspectral imaging.
Publisher: Wiley
Date: 02-2017
DOI: 10.1111/IMJ.13325
Publisher: MDPI AG
Date: 13-12-2019
DOI: 10.3390/JCM8122199
Abstract: Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Atherosclerosis develops over several decades and is mediated by a complex interplay of cellular mechanisms that drive a chronic inflammatory milieu and cell-to-cell interactions between endothelial cells, smooth muscle cells and macrophages that promote plaque development and progression. While there has been significant therapeutic advancement, there remains a gap where novel therapeutic approaches can complement current therapies to provide a holistic approach for treating atherosclerosis to orchestrate the regulation of complex signalling networks across multiple cell types and different stages of disease progression. MicroRNAs (miRNAs) are emerging as important post-transcriptional regulators of a suite of molecular signalling pathways and pathophysiological cellular effects. Furthermore, circulating miRNAs have emerged as a new class of disease biomarkers to better inform clinical diagnosis and provide new avenues for personalised therapies. This review focusses on recent insights into the potential role of miRNAs both as therapeutic targets in the regulation of the most influential processes that govern atherosclerosis and as clinical biomarkers that may be reflective of disease severity, highlighting the potential theranostic (therapeutic and diagnostic) properties of miRNAs in the management of cardiovascular disease.
Publisher: SPIE
Date: 09-12-2016
DOI: 10.1117/12.2244642
Publisher: Elsevier BV
Date: 05-2023
Publisher: Springer Science and Business Media LLC
Date: 08-02-2019
DOI: 10.1038/S41598-019-39123-3
Abstract: Nitric oxide (NO) is a key regulator of endothelial cell and vascular function. The direct measurement of NO is challenging due to its short half-life, and as such surrogate measurements are typically used to approximate its relative concentrations. Here we demonstrate that ruthenium-based [Ru(bpy) 2 (dabpy)] 2+ is a potent sensor for NO in its irreversible, NO-bound active form, [Ru(bpy) 2 (T-bpy)] 2+ . Using spectrophotometry we established the sensor’s ability to detect and measure soluble NO in a concentration-dependent manner in cell-free media. Endothelial cells cultured with acetylcholine or hydrogen peroxide to induce endogenous NO production showed modest increases of 7.3 ± 7.1% and 36.3 ± 25.0% respectively in fluorescence signal from baseline state, while addition of exogenous NO increased their fluorescence by 5.2-fold. The changes in fluorescence signal were proportionate and comparable against conventional NO assays. Rabbit blood s les immediately exposed to [Ru(bpy) 2 (dabpy)] 2+ displayed 8-fold higher mean fluorescence, relative to blood without sensor. Approximately 14% of the observed signal was NO/NO adduct-specific. Optimal readings were obtained when sensor was added to freshly collected blood, remaining stable during subsequent freeze-thaw cycles. Clinical studies are now required to test the utility of [Ru(bpy) 2 (dabpy)] 2+ as a sensor to detect changes in NO from human blood s les in cardiovascular health and disease.
Publisher: Japanese Circulation Society
Date: 2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2012
DOI: 10.1161/ATVBAHA.111.243733
Abstract: Tissue factor pathway inhibitor (TFPI) is the primary regulator of the tissue factor (TF) coagulation pathway. As such, TFPI may regulate the proangiogenic effects of TF. TFPI may also affect angiogenesis independently of TF, through sequences within its polybasic carboxyl terminus (TFPI C terminus [TFPIct]). We aimed to determine the effects of TFPI on angiogenesis and the role of TFPIct. Transgenic overexpression of TFPI attenuated angiogenesis in the murine hindlimb ischemia model and an aortic sprout assay. In vitro, TFPI inhibited endothelial cell migration. Peptides within the human TFPIct inhibited endothelial cell cord formation and migration in response to vascular endothelial growth factor (VEGF) 165 but not VEGF121. Furthermore, exposure to human TFPIct inhibited the phosphorylation of VEGF receptor 2 at residue Lys951, a residue known to be critical for endothelial cell migration. Finally, systemic delivery of a murine TFPIct peptide inhibited angiogenesis in the hindlimb model. These data demonstrate an inhibitory role for TFPI in angiogenesis that is, in part, mediated through peptides within its carboxyl terminus. In addition to its known role as a TF antagonist, TFPI, via its carboxyl terminus, may regulate angiogenesis by directly blocking VEGF receptor 2 activation and attenuating the migratory capacity of endothelial cells.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.JCIN.2010.05.016
Abstract: This study set out to evaluate the safety and efficacy of allogeneic bone marrow mesenchymal precursor cells (MPC) delivered by multisegmental, transendocardial implantation in the setting of nonischemic cardiomyopathy (NICM). Prospectively isolated MPC have shown capacity to mediate cardiovascular repair in myocardial ischemia. However, their efficacy in NICM remains undetermined. Mesenchymal precursor cells were prepared from ovine bone marrow by immunoselection using the tissue nonspecific alkaline phosphatase, or STRO-3, monoclonal antibody. Fifteen sheep with anthracycline-induced NICM were assigned to catheter-based, transendocardial injections of allogeneic MPC (n = 7) or placebo (n = 8), under electromechanical mapping guidance. Follow-up was for 8 weeks, with end points assessed by cardiac magnetic resonance, echocardiography, and histology. Intramyocardial injections were distributed similarly throughout the left ventricle in both groups. Cell transplantation was associated with 1 death late in follow-up, compared with 3 early deaths among placebo animals. Left ventricular end-diastolic size increased in both cohorts, but MPC therapy attenuated end-systolic dilation and stabilized ejection fraction, with a nonsignificant increase (37.3 ± 2.8% before, 39.2 ± 1.4% after) compared with progressive deterioration after placebo (38.8 ± 4.4% before, 32.5 ± 4.9% after, p < 0.05). Histological outcomes of cell therapy included less fibrosis burden than in the placebo group and an increased density of karyokinetic cardiomyocytes and myocardial arterioles (p < 0.05 for each). These changes occurred in the presence of modest cellular engraftment after transplantation. Multisegmental, transendocardial delivery of cell therapy can be achieved effectively in NICM using electromechanical navigation. The pleiotropic properties of immunoselected MPC confer benefit to nonischemic cardiac disease, extending their therapeutic potential beyond the setting of myocardial ischemia.
Publisher: Elsevier BV
Date: 07-2017
Publisher: Elsevier BV
Date: 11-2012
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.HRTHM.2010.12.009
Abstract: It has been suggested that omega-3 polyunsaturated fatty acids (n-3 PUFAs) may prevent the development of atrial fibrillation (AF). The purpose of this study was to evaluate the impact of these agents on development of the AF substrate in heart failure (HF). In this study, HF was induced by intracoronary doxorubicin infusions. Twenty-one sheep [7 with n-3 PUFAs treated HF (HF-PUFA), 7 with olive oil-treated HF controls (HF-CTL), 7 controls (CTL)] were studied. Open chest electrophysiologic study was performed with assessment of biatrial effective refractory period (ERP) and conduction. Cardiac function was monitored by magnetic resonance imaging. Atrial n-3 PUFAs levels were quantified using chromatography. Structural analysis was also performed. Atrial n-3 PUFAs levels were twofold to threefold higher in the HF-PUFA group. n-3 PUFAs prevented the development of HF-related left atrial enlargement (P = .001) but not left ventricular/atrial dysfunction. Atrial ERP was significantly lower in the HF-PUFA group (P <.001), but ERP heterogeneity was unchanged. In addition, n-3 PUFAs suppressed atrial conduction abnormalities seen in HF of prolonged P-wave duration (P = .01) and slowed (P <.001) and heterogeneous (P <.05) conduction. The duration of induced AF episodes in HF-PUFA was shorter (P = .02), although AF inducibility was unaltered (P = NS). A 20% reduction of atrial interstitial fibrosis was seen in the HF-PUFA group (P <.05). In this ovine HF study, chronic n-3 PUFAs use protected against adverse atrial remodeling by preventing atrial enlargement, fibrosis, and conduction abnormalities leading to shorter AF episodes despite lower ERP.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2020
DOI: 10.1007/S10557-020-07106-6
Abstract: Atherosclerotic coronary artery disease has a complex pathogenesis which extends beyond cholesterol intimal infiltration. It involves chronic inflammation of the coronary artery wall driven by systemic and local activation of both the adaptive and innate immune systems, which can ultimately result in the rupture or erosion of atherosclerotic plaque, leading to thrombosis and myocardial infarction (MI). Despite current best practice care, including the widespread use of cholesterol-lowering statins, atherothrombotic cardiovascular events recur at alarming rates post-MI. To a large extent, this reflects residual inflammation that is not adequately controlled by contemporary treatment. Consequently, there has been increasing interest in the pharmacological targeting of inflammation to improve outcomes in atherosclerotic cardiovascular disease. This has comprised both novel pathway-specific agents, most notably the anti-interleukin-1 beta monoclonal antibody, canakinumab, and the repurposing of established, broad-acting drugs, such as colchicine, that are already approved for the management of other inflammatory conditions. Here we discuss the importance of inflammation in mediating atherosclerosis and its complications and provide a timely update on "new" and "old" anti-inflammatory therapies currently being investigated to target it.
Publisher: Oxford University Press (OUP)
Date: 03-04-2020
DOI: 10.1093/EURHEARTJ/EHAA173
Abstract: Intravascular ultrasound (IVUS) imaging can visualize vulnerable plaque features including attenuation (AP) and echolucency (ELP). While IVUS-derived vulnerable plaque features associate with microvascular obstruction during percutaneous coronary intervention, the relationship between these plaque features and clinical outcomes has not been established. This analysis aimed to evaluate the association of AP/ELP with cardiovascular events. Serial IVUS imaging was reviewed in 1497 patients, followed for 18–24 months, with coronary artery disease from two clinical trials. Attenuated plaque and ELP were identified to measure each characteristics (AP arc, ELP area, and lengths), which permitted calculation of an AP index (API) and ELP volume. Attenuated plaque/ELP progression was defined as patients with any increase of API or ELP volume on serial imaging. The major cardiovascular events (MACEs) were defined as death, myocardial infarction, stroke, and coronary revascularization. AP or ELP was identified in 282 patients (18.8%) at baseline and 160 (10.7%) patients demonstrated an increase in AP or ELP at follow-up. The incidence of MACE was higher in patients with baseline AP/ELP than those without (8.2% vs. 3.9%, P = 0.002). Patients with AP/ELP progression were more likely to be acute coronary syndrome (41.9 vs. 33.2%, P = 0.03) and have greater baseline percent atheroma volume (40.0% vs. 35.8%, P & 0.001) than those without. On multivariable analysis, AP/ELP progression was more strongly associated with MACE [baseline AP/ELP: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.05–2.97, AP/ELP progression: HR 2.19, 95% CI 1.24–3.86]. Attenuation/ELP progression was associated with a higher prevalence of cardiovascular events, supporting a potential role for the identification of high-risk vulnerable plaques in patients with coronary artery disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-11-2020
Abstract: Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery‐related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer‐reviewed, English publications reporting post‐CABG delirium or cognitive decline data, for at least one risk factor. Random‐effects meta‐analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety‐seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1–6 months) post‐CABG cognitive decline. This meta‐analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable. URL: www.crd.york.ac.uk rospero/ Unique identifier: CRD42020149276.
Publisher: Elsevier BV
Date: 12-2018
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.TCM.2018.04.007
Abstract: Coronary artery calcification (CAC) was once thought to be a passive, degenerative, and quiescent development of disease. However, it has now been shown to be an active process associated with atherosclerosis that is stimulated by inflammatory pathways. Calcification forms within the intimal and medial layers of the vessel wall by way of mechanisms similar to bone development. A variety of imaging modalities have been used to identify and characterize CAC, from early microcalcifications to well-developed fibroatheromas that have calcified. There are sex and race differences in prevalence and development of CAC, and medical therapies such as statin and warfarin use exhibit pro-calcific effects on the vessel wall. Effective medical treatment of CAC has yet to be established therefore a greater understanding of the factors that induce calcification is needed to develop appropriate therapeutic strategies.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.ATHEROSCLEROSIS.2017.08.016
Abstract: Little is known about the relation between serum lipid parameters and serial change in plaque composition using in vivo coronary imaging. The aim of this study was to examine the association between serum lipids and change in coronary plaque lipid burden assessed by near-infrared spectroscopy (NIRS). We performed serial NIRS-intravascular ultrasound studies in 49 patients who underwent coronary angiography for an acute coronary syndrome (ACS) or stable ischemic symptoms. Univariable and multivariable linear regression analyses were applied to evaluate the relationship between serum lipid parameters and change in lipid core burden index at the 4-mm maximal segment (max LCBI Mean patient age was 61 ± 9 y, 29% were women, 35% had an ACS clinical presentation, 78% received statin therapy at baseline, and median low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), total cholesterol and triglyceride levels were 101, 43, 174 and 133 mg/dL, respectively. During a median follow-up period of 13 months, max LCBI Change in HDL-C, but not other lipids parameters, associated with changes in coronary plaque lipid burden assessed by NIRS. These findings highlight the potential therapeutic importance of high-density lipoprotein on serial change in plaque composition.
Publisher: Portland Press Ltd.
Date: 31-07-2020
DOI: 10.1042/BCJ20200433
Abstract: The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are serine/threonine protein kinases that are activated by the ERK1/2 (extracellular regulated kinase) and p38α/β MAPK pathways. The MNKs have previously been implicated in metabolic disease and shown to mediate diet-induced obesity. In particular, knockout of MNK2 in mice protects from the weight gain induced by a high-fat diet. These and other data suggest that MNK2 regulates the expansion of adipose tissue (AT), a stable, long-term energy reserve that plays an important role in regulating whole-body energy homeostasis. Using the well-established mouse 3T3-L1 in vitro model of adipogenesis, the role of the MNKs in adipocyte differentiation and lipid storage was investigated. Inhibition of MNK activity using specific inhibitors failed to impair adipogenesis or lipid accumulation, suggesting that MNK activity is not required for adipocyte differentiation and does not regulate lipid storage. However, small-interfering RNA (siRNA) knock-down of MNK2 did reduce lipid accumulation and regulated the levels of two major lipogenic transcriptional regulators, ChREBP (carbohydrate response element-binding protein) and LPIN1 (Lipin-1). These factors are responsible for controlling the expression of genes for proteins involved in de novo lipogenesis and triglyceride synthesis. The knock-down of MNK2 also increased the expression of hormone-sensitive lipase which catalyses the breakdown of triglyceride. These findings identify MNK2 as a regulator of adipocyte metabolism, independently of its catalytic activity, and reveal some of the mechanisms by which MNK2 drives AT expansion. The development of an MNK2-targeted therapy may, therefore, be a useful intervention for reducing weight caused by excessive nutrient intake.
Publisher: AME Publishing Company
Date: 06-2019
Publisher: Elsevier BV
Date: 07-2019
Publisher: Oxford University Press (OUP)
Date: 19-07-2018
Abstract: The durable polymer (DP) of a drug-eluting stent (DES) serves no function once drug elution is complete. To ascertain the benefits of bioabsorbable polymer (BP) over DP-DESs requires a longer follow-up period, to overcome the time taken for polymer absorption. The primary aim of this meta-analysis was to compare the safety and efficacy of BP-DES with the DP-DES over mid (2 years) to long-term (3-5 years) follow-up. A thorough computer-based search was performed using Ovid MEDLINE, EMBASE, Google Scholar, and PubMed databases. We only included randomized controlled studies comparing clinical outcomes between BP-DESs and DP-DESs. Only studies where data were available for a minimum of 2 years were included. A separate analysis of 2-year outcomes and 3- to 5-year outcomes were conducted. Data from 6 and 8 studies were included in 3- to 5-year and 2-year follow-up, respectively. There were no differences between stent groups in cardiac mortality, stent thrombosis (ST), target lesion revascularization, target vessel failure, and reinfarction rates for either 2-year or 3- to 5-year follow-up. Subgroup analysis according to strut thickness ( 100 µm) of BP-DES demonstrated similar results. The analyses of ST and very late ST favoured BP-DESs but did not reach statistically significant level. There were no differences in clinical outcomes between BP-DESs and DP-DESs over mid- and long-term follow-up.
Publisher: Informa UK Limited
Date: 12-06-2008
DOI: 10.1080/10550880802122596
Abstract: There has been recent concern about the association between high dose methadone and prolongation of QTc in the electrocardiogram. QTc is the time from the beginning of the QRS complex to the end of the T have as measured on an electrocardiogram and corrected for heart rate. To date, no association has been made between methadone and buprenorphine in commonly used doses and prolonged QTc. Electrocardiograms were performed on groups of methadone (n = 35, mean daily dose +/- standard deviation, 69 +/- 29 mg) and buprenorphine (n = 19, mean daily dose 11 +/- 5 mg) subjects and a group of non-opioid dependent controls (n = 17). Mean QTc did not differ (p = 0.45) between methadone, buprenorphine, or controls. Methadone subjects were significantly (odds ratio of 7.8) more likely to have U waves than buprenorphine and controls combined. Methadone subjects with U waves were maintained on higher (p = 0.004) doses (89 +/- 29 mg/day) than methadone subjects without U waves (60 +/- 24 mg/day). Methadone subjects taking 60 mg and above had higher (p = 0.02) QTc (405 +/- 29 milliseconds) than methadone subjects taking less than 60 mg per day (381 +/- 27 milliseconds). Although an association is thought to exist between high methadone doses and elongated QTc, methadone and buprenorphine, at commonly used daily doses, remain safe agents for opioid substitution therapy.
Publisher: Springer Science and Business Media LLC
Date: 02-03-2021
DOI: 10.1007/S00125-021-05414-6
Abstract: Diabetes is a major burden on Australia's Indigenous population, with high rates of disease and vascular complications. Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. MicroRNAs (miRNAs) are key players in the regulation of angiogenesis. HDL-cholesterol (HDL-c) levels are inversely associated with the risk of developing diabetic complications and HDL can carry miRNAs. HDL-miRNA profiles differ in disease states and may present as biomarkers with the capacity to act as bioactive signalling molecules. Recent studies have demonstrated that HDL becomes dysfunctional in a diabetic environment, losing its vasculo-protective effects and becoming more pro-atherogenic. We sought to determine whether HDL-associated miRNA profiles and HDL functionality were predictive of the severity of diabetic vascular complications in Australia's Indigenous population. HDL was isolated from plasma s les from Indigenous participants without diabetes ('Healthy'), with type 2 diabetes mellitus ('T2DM') and with diabetes-associated macrovascular complications (specifically peripheral artery disease, 'T2DM+Comp'). To assess HDL angiogenic capacity, human coronary artery endothelial cells were treated with PBS, reconstituted HDL (rHDL, positive control) or isolated HDL and then exposed to high-glucose (25 mmol/l) conditions. The expression levels of two anti-angiogenic miRNAs (miR-181c-5p and miR-223-3p) and one pro-angiogenic miRNA (miR-27b-3p) were measured in the HDL fraction, plasma and treated human coronary artery endothelial cells by quantitative real-time PCR. In vitro endothelial tubule formation was assessed using the Matrigel tubulogenesis assay. Strikingly, we found that the levels of the anti-angiogenic miRNA miR-181c-5p were 14-fold higher (1454 ± 1346%) in the HDL from Aboriginal people with diabetic complications compared with both the Healthy (100 ± 121%, p < 0.05) and T2DM (82 ± 77%, p < 0.05) groups. Interestingly, we observed a positive correlation between HDL-associated miR-181c-5p levels and disease severity (p = 0.0020). Under high-glucose conditions, cells treated with rHDL, Healthy HDL and T2DM HDL had increased numbers of tubules (rHDL: 136 ± 8%, p < 0.01 Healthy HDL: 128 ± 6%, p < 0.01 T2DM HDL: 124 ± 5%, p < 0.05) and branch points (rHDL: 138 ± 8%, p < 0.001 Healthy HDL: 128 ± 6%, p < 0.01 T2DM HDL: 127 ± 5%, p < 0.01) concomitant with elevations in mRNA levels of the key hypoxia angiogenic transcription factor HIF1A (rHDL: 140 ± 10%, p < 0.01 Healthy HDL: 136 ± 8%, p < 0.01 T2DM HDL: 133 ± 9%, p < 0.05). However, this increase in angiogenic capacity was not observed in cells treated with T2DM + Comp HDL (tubule numbers: 113 ± 6%, p = 0.32 branch points: 113 ± 5%, p = 0.28 HIF1A: 117 ± 6%, p = 0.43), which could be attributed to the increase in cellular miR-181c-5p levels (T2DM + Comp HDL: 136 ± 7% vs PBS: 100 ± 9%, p < 0.05). In conclusion, HDL from Aboriginal people with diabetic complications had reduced angiogenic capacity. This impairment is associated with an increase in the expression of anti-angiogenic miR-181c-5p. These findings provide the rationale for a new way to better inform clinical diagnosis of disease severity with the potential to incorporate targeted, personalised HDL-miRNA intervention therapies to prevent further development of, or to reverse, diabetic vascular complications in Australian Aboriginal people.
Publisher: Wiley
Date: 10-2009
DOI: 10.1111/J.1445-5994.2008.01876.X
Abstract: Heart failure is a growing health issue and is associated with significant mortality risk. Device therapy is efficacious in preventing sudden death in patients with heart failure however, this evidence comes from rigorous clinical trials. It is unclear how device therapy is utilized in 'real-world' practice. The primary objective was to characterize patterns of device use in patients with heart failure at risk of sudden death and to identify barriers to guideline-driven prescription of implantable cardioverter-defibrillators. We report a cross-sectional study of patients attending general cardiology clinic over a 3-month period. Of 1003 consecutive patients attending the cardiology clinic, 176 had heart failure. Of these, 66 were potentially eligible for device therapy, but only 16 of these had actually undergone device implantation. Potentially eligible non-recipients were older (P 120 ms (P= 0.005). There was a high prevalence of underuse of evidence-based pharmacotherapies among patients with heart failure. There is substantial underuse of device therapy in patients with heart failure. Strikingly, whereas patients with symptoms of heart failure were more likely to receive a device, those being managed for ischaemic heart disease were not. There is also a high prevalence of failure to prescribe evidence-based pharmacotherapy in a tertiary hospital general cardiology clinic. This may be explained in part by the lack of a patient database to record treatment contraindications and to alert clinicians to possible gaps in patient therapy.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.HLC.2015.12.101
Abstract: Chronic total occlusions (CTOs) represent a unique set of lesions for percutaneous coronary intervention (PCI) because of the complexity of techniques required to treat them. We retrospectively reviewed the CTO-PCI experience between January 2010 and December 2012, in a multi-operator single centre, which is one of the largest volume PCI centres in Australia. Eighty-two patients (62.6±11.3 years, 85% males) who had CTO-PCIs were included. The most common site of CTO was the right coronary artery (44%), followed by the left circumflex (30%) and left anterior descending (26%) arteries. Using the Japanese CTO scoring system, 34% of lesions were classified as easy, 37% intermediate, 23% difficult and 6% very difficult. All PCIs were performed by antegrade approach. Selected procedural characteristics included: re-attempt procedure 10% multiple access sites 21% more than one guidewire 77% additional support modality 60% drug-eluting stents 97% stent number 1.6±0.8 total stent length 40.1±24.5mm fluoroscopy time 33±17min contrast volume 257.2±110.8mL. Overall CTO success rate was 60%. In-hospital adverse outcomes included 1.2% mortality, 9.8% peri-procedural myocardial infarction, 4.9% emergency bypass surgery, 3% cardiac t onade and 4.9% contrast induced nephropathy. We report modest success rates in a single Australian centre experience in a relatively conservative cohort of CTO-PCI prior to the initiation of a dedicated CTO revascularisation program.
Publisher: Informa UK Limited
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 06-01-2021
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.IJCARD.2018.06.022
Abstract: Visual assessment of diameter-stenosis on Computed Tomography Coronary Angiography (CTCA) lacks specificity to determine functional significance of coronary artery stenosis. Percent-aggregate plaque volume (%APV) and ASLA score, which incorporates Area of Stenosis, Lesion length, and area of myocardium subtended estimated by APPROACH score (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease) have been described to predict lesion specific ischaemia in focal lesions with intermediate stenosis. Included were 81 patients (mean age 64.7 ± 9 years, 62% male 94 vessels) who underwent 320- detector-row CTCA, invasive coronary angiography and fractional-flow-reserve (FFR). We examined vessels with wide range of diameter stenosis (mid to severe) and with multiple lesions. Invasive FFR of ≤0.8 was considered functionally significant. The first 54 patients (62 vessels) formed the derivation cohort. ASLA score was the best predictor of FFR ≤ 0.8 (AUC 0.83, p 50% (0.76), APPROACH score (0.79), area-stenosis (0.73), diameter-stenosis (0.74), minimum-luminal-diameter (0.74), minimal-luminal-area (0.72), and lesion-length (0.67). ASLA score and not %APV, provided incremental predictive value when added to CT > 50 [(NRI 0.71, p = 0.005) vs. (NRI 0.01, p = 0.96)]. In the validation cohort of 27 patients (32 vessels), the ASLA score (AUC 0.85) was again a better predictor of FFR ≤ 0.8 compared to %APV (0.71), CT > 50% (0.66) and other CT indices. The AUC of ASLA score was superior to CTCA>50% (p = 0.001). ASLA score is a novel predictor of functional significance of coronary stenosis and adds incremental predictive value to CT > 50 but %APV did not.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.HLC.2016.09.002
Abstract: Older in iduals can now undergo invasive cardiovascular procedures without serious concern about mortality, and the numbers and proportions of the over 65s and 85s doing so in Australia has been increasing over the last 20 years. There is overwhelming evidence linking cardiovascular conditions to late-life (65 years and over) cognitive impairment and dementia including Alzheimer's Disease, primarily due to impaired cerebrovascularisation and cascading neuropathological processes. Somewhat paradoxically, these cardiovascular interventions, carried out with the primary aim of revascularisation, are not usually associated with short- or long-term improvements in cognitive function in older adults. We discuss factors associated with cognitive outcomes post-cardiovascular surgeries in patients over 65 years of age. There are many opportunities for future research: we know almost nothing about cognitive outcomes following invasive cardiac procedures in the oldest old (85 years and over) nor how to predict the cognitive/delirium outcome using pre-surgical data, and lastly, intervention opportunities exist both pre and postoperatively that have not been tested. As our population ages with increased cardiovascular burden and rates of cardiovascular interventions and surgeries, it is critical that we understand the cognitive consequences of these procedures, who is at greatest risk, and ways to optimise cognition.
Publisher: Elsevier BV
Date: 11-2016
Publisher: Oxford University Press (OUP)
Date: 03-07-2008
DOI: 10.1634/STEMCELLS.2008-0428
Abstract: Cellular therapy for cardiovascular disease heralds an exciting frontier of research. Mesenchymal stromal cells (MSCs) are present in adult tissues, including bone marrow and adipose, from which they can be easily isolated and cultured ex vivo. Although traditional isolation of these cells by plastic adherence results in a heterogeneous composite of mature and immature cell types, MSCs do possess plasticity of differentiation and under appropriate in vitro culture conditions can be modified to adopt cardiomyocyte and vascular cell phenotypic characteristics. In vivo preclinical studies have demonstrated their capacity to facilitate both myocardial repair and neovascularization in models of cardiac injury. The mechanisms underlying these effects appear to be mediated predominantly through indirect paracrine actions, rather than direct regeneration of endogenous cells by transdifferentiation, especially because current transplantation strategies achieve only modest engraftment of cells in the host myocardium. Currently, published clinical trial experience of MSCs as cardiac therapy is limited, and the outcomes of ongoing studies are keenly anticipated. Of relevance to clinical application is the fact that MSCs are relatively immunoprivileged, potentially enabling their allogeneic therapeutic use, although this too requires further investigation. Overall, MSCs are an attractive adult-derived cell population for cardiovascular repair however, research is still required at both basic and clinical levels to resolve critical areas of uncertainty and to ensure continued development in cell culture engineering and cell transplantation technology. Disclosure of potential conflicts of interest is found at the end of this article.
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.CARDFAIL.2012.03.005
Abstract: Cumulative dose-dependent nonischemic cardiomyopathy (NICM) remains a significant risk with the use of some chemotherapeutic agents. In this context, omega-3 polyunsaturated fatty acids (PUFA) have been investigated for their cardioprotective potential in rodent and in vitro models of anthracycline toxicity, with conflicting results. This study evaluated prophylactic omega-3 PUFA supplementation in a large-animal model of anthracycline-induced NICM. Merino sheep were randomized to oral drenching with omega-3 PUFA (fish oil n = 8) or olive oil placebo (n = 9) 3 weeks before commencing repeated intracoronary infusions of doxorubicin (DOX) to induce cardiac dysfunction. Cumulative DOX dose was 3.6 mg/kg. Drenching was continued for 12 weeks after final DOX exposure. Despite significant increases in tissue omega-3 PUFA levels (P < .05 vs placebo), omega-3-treated sheep displayed greater signs of anthracycline cardiotoxicity than placebo animals, consisting of left ventricular dilatation and a greater decline in ejection fraction (P < .05), although myocardial fibrosis burden was similar in both groups. Dietary intake of omega-3 PUFA fails to prevent and may indeed exacerbate DOX-induced cardiotoxicity. Clinical use of omega-3 supplementation during chemotherapy should be deferred until more information is available regarding the mechanisms of interaction between fatty acids and the myocardium during anthracycline exposure.
Publisher: American Medical Association (AMA)
Date: 03-04-2018
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 2016
Publisher: Elsevier BV
Date: 07-2020
Publisher: SAGE Publications
Date: 2019
Abstract: Despite its commonality in routine clinical practice, the approach to a diagnosis of atherosclerotic coronary artery disease remains complex and, in part, contentious. The traditional dogma linking ischaemia to hard clinical outcomes has been questioned and reframed over the years rather than being a predictor of hard clinical outcomes, the degree of ischaemia may simply be a marker of atherosclerotic disease burden. A renewed interest in the imaging of plaque burden has spawned the contemporary role of CT imaging for not only diagnosis and prognosis, but also for dictating downstream management. As the technology develops and evidence expands, decisions on investigative modalities remain centred around patient factors, local availability, test performance and cost. This review summarizes the available methods for diagnosis in the symptomatic patient and provides an overview of the current evidence behind functional and anatomical approaches.
Publisher: SAGE Publications
Date: 2008
DOI: 10.4137/CMC.S571
Publisher: Springer Science and Business Media LLC
Date: 10-12-2009
DOI: 10.1007/S12265-008-9080-7
Abstract: Combined analysis of the electrical and mechanical function of the heart holds promise as a means of acquiring a better understanding of a variety of cardiac diseases that ultimately may lead to heart failure. The NOGA XP Cardiac Navigation System is a unique, nonfluoroscopic, catheter-based technology that achieves real-time acquisition of three-dimensional, endoventricular electromechanical maps. Through the provision of point-by-point measurements of endocardial electrical activation and voltage and mechanical shortening, electromechanical mapping has been evaluated for its ability to identify regional myocardial ischemia and characterize tissue viability. A decade of preclinical and clinical research has verified its safety and feasibility and raised the possibility of its application as a diagnostic adjunct to conventional angiography in the catheterization laboratory. However, this role has not yet been realized outside of the research setting. Instead, a more prominent niche for NOGA XP has emerged as a therapeutic tool for guiding direct myocardial interventions, most notably the targeted administration of regenerative therapies (e.g., cells, genes) to the heart. In this review, we discuss the fundamental aspects of this electromechanical mapping system and the evidence for both its diagnostic and therapeutic utility.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 06-2020
DOI: 10.1016/J.HLC.2019.06.719
Abstract: To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06±0.07, p=0.44 Bland-Altman 95% limits of agreement -2.19-2.08 mm Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.
Publisher: AME Publishing Company
Date: 02-2017
Publisher: Elsevier BV
Date: 2018
Publisher: Wiley
Date: 03-2022
Abstract: Multimodal microendoscopes enable co‐located structural and molecular measurements in vivo, thus providing useful insights into the pathological changes associated with disease. However, different optical imaging modalities often have conflicting optical requirements for optimal lens design. For ex le, a high numerical aperture (NA) lens is needed to realize high‐sensitivity fluorescence measurements. In contrast, optical coherence tomography (OCT) demands a low NA to achieve a large depth of focus. These competing requirements present a significant challenge in the design and fabrication of miniaturized imaging probes that are capable of supporting high‐quality multiple modalities simultaneously. An optical design is demonstrated which uses two‐photon 3D printing to create a miniaturized lens that is simultaneously optimized for these conflicting imaging modalities. The lens‐in‐lens design contains distinct but connected optical surfaces that separately address the needs of both fluorescence and OCT imaging within a lens of 330 µm diameter. This design shows an improvement in fluorescence sensitivity of x in contrast to more conventional fiber‐optic design approaches. This lens‐in‐lens is then integrated into an intravascular catheter probe with a diameter of 520 µm. The first simultaneous intravascular OCT and fluorescence imaging of a mouse artery in vivo is reported.
Publisher: Springer International Publishing
Date: 2021
Publisher: MDPI AG
Date: 26-07-2019
DOI: 10.3390/JCM8081109
Abstract: Atherosclerotic coronary artery disease (CAD) results from build-up of cholesterol-rich plaques in the walls of the coronary arteries and is a leading cause of death. Inflammation is central to atherosclerosis. Uncontrolled inflammation makes coronary plaques “unstable” and vulnerable to rupture or erosion, leading to thrombosis and myocardial infarction (MI). As multiple inflamed plaques often co-exist in the coronary system, patients are at risk of repeated atherothrombotic cardiovascular events after MI, with rates of 10–12% at one year and 18–20% at three years. This is largely because current therapies for CAD, such as lipid-lowering statins, do not adequately control plaque inflammation. New anti-atherosclerotic agents are therefore needed, especially those that better target inflammation. The recent positive results for the anti-interleukin-1-beta (IL-1β) monoclonal antibody, Canakinumab, in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) clinical trial has provided a major stimulant to the field. It highlights that not only is inflammation important from a pathogenic and risk prediction perspective in CAD, but that reducing inflammation can be beneficial. The challenge is now to find the best strategies to achieve this in real-world practice. This review outlines the role that inflammation plays in atherosclerosis and provides an update on anti-inflammatory therapies currently being investigated to target atherosclerosis.
Publisher: Springer International Publishing
Date: 2021
Publisher: SAGE Publications
Date: 2008
Publisher: Springer Science and Business Media LLC
Date: 28-08-2018
DOI: 10.1007/S40256-018-0298-8
Abstract: Apabetalone is a selective bromodomain and extra-terminal (BET) inhibitor which modulates lipid and inflammatory pathways implicated in atherosclerosis. The impact of apabetalone on attenuated coronary atherosclerotic plaque (AP), a measure of vulnerability, is unknown. The ApoA-1 Synthesis Stimulation and intravascular Ultrasound for coronary atheroma Regression Evaluation (ASSURE NCT01067820) study employed serial intravascular ultrasound (IVUS) measures of coronary atheroma in 281 patients treated with apabetalone or placebo for 26 weeks. AP was measured at baseline and follow-up. Factors associated with changes in AP were investigated. AP was observed in 31 patients (11%) [27 (13.0%) in the apabetalone group and four (5.5%) in the placebo group]. The apabetalone group demonstrated reductions in AP length by - 1 mm [interquartile range (IQR) - 4, 1] (p = 0.03), AP arc by - 37.0° (IQR - 59.2, 8.2) (p = 0.003) and the AP index by - 34.6 mm° (IQR - 52.6, 10.1) (p = 0.003) from baseline. The change in AP index correlated with on-treatment concentration of high-density lipoprotein (HDL) particles (r = - 0.52, p = 0.006), but not HDL cholesterol (r = - 0.11, p = 0.60) or apolipoprotein A-1 (r = - 0.16, p = 0.43). Multivariable analysis revealed that on-treatment concentrations of HDL particles (p = 0.03) and very low-density lipoprotein particles (p = 0.01) were independently associated with changes in AP index. Apabetalone favorably modulated ultrasonic measures of plaque vulnerability in the population studied, which may relate to an increase in HDL particle concentrations. The clinical implications are currently being investigated in the phase 3 major adverse cardiac event outcomes trial BETonMACE.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2016
Publisher: Springer Science and Business Media LLC
Date: 13-04-2012
DOI: 10.1007/S12015-012-9366-7
Abstract: Despite current treatment options, cardiac failure is associated with significant morbidity and mortality highlighting a compelling clinical need for novel therapeutic approaches. Based on promising pre-clinical data, stem cell therapy has been suggested as a possible therapeutic strategy. Of the candidate cell types evaluated, mesenchymal stromal/stem cells (MSCs) have been widely evaluated due to their ease of isolation and ex vivo expansion, potential allogeneic utility and capacity to promote neo-angiogenesis and endogenous cardiac repair. However, the clinical application of MSCs for mainstream cardiovascular use is currently hindered by several important limitations, including suboptimal retention and engraftment and restricted capacity for bona fide cardiomyocyte regeneration. Consequently, this has prompted intense efforts to advance the therapeutic properties of MSCs for cardiovascular disease. In this review, we consider the scope of benefit from traditional plastic adherence-isolated MSCs and the lessons learned from their conventional use in preclinical and clinical studies. Focus is then given to the evolving strategies aimed at optimizing MSC therapy, including discussion of cell-targeted techniques that encompass the preparation, pre-conditioning and manipulation of these cells ex vivo, methods to improve their delivery to the heart and innovative substrate-directed strategies to support their interaction with the host myocardium.
Publisher: Elsevier BV
Date: 07-2013
Publisher: BMJ
Date: 20-01-2016
Publisher: MDPI AG
Date: 20-08-2020
DOI: 10.3390/JCM9092694
Abstract: Timing of aortic valve intervention for chronic aortic regurgitation (AR) and/or aortic stenosis (AS) potentially affects long-term survival. The 2014 American Heart Association/American College of Cardiology (AHA/ACC) guidelines provide recommendations for the timing of intervention. Subsequent to the guidelines’ release, several studies have been published that suggest a survival benefit from earlier timing of surgery for severe AR and/or AS. The aim of this review was to determine whether patients who have chronic aortic regurgitation (AR) and/or aortic stenosis (AS) have a survival benefit from earlier timing of aortic valve surgery. Medical databases were systematically searched from January 2015 to April 2020 for randomized controlled trials (RCTs) and observational studies that examined the timing of aortic valve replacement surgery for chronic AR and/or AS. For chronic AR, four observational studies and no RCTs were identified. For chronic AS, five observational studies, one RCT and one meta-analysis were identified. One observational study examining mixed aortic valve disease (MAVD) was identified. All of these studies, for AR, AS, and MAVD, found long-term survival benefit from timing of aortic valve surgery earlier than the current guidelines. Larger prospective RCTs are required to evaluate the benefit of earlier surgical intervention.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.JCYT.2013.07.016
Abstract: Traditionally, stem cell therapy for myocardial infarction (MI) has been administered as a single treatment in the acute or subacute period after MI. These time intervals coincide with marked differences in the post-infarct myocardial environment, raising the prospect that repeat cell dosing could provide incremental benefit beyond a solitary intervention. This prospect was evaluated with the use of mesenchymal stromal cells (MSCs). Three groups of rats were studied. Single-therapy and dual-therapy groups received allogeneic, prospectively isolated MSCs (1 × 10(6) cells) by trans-epicardial injection immediately after MI, with additional dosing 1 week later in the dual-therapy cohort. Control animals received cryopreservant solution only. Left ventricular (LV) dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance immediately before MI and at 1, 2 and 4 weeks after MI. Immediate MSC treatment attenuated early myocardial damage with EF of 35.3 ± 3.1% (dual group, n = 12) and 35.2 ± 2.2% (single group, n = 15) at 1 week after MI compared with 22.1 ± 1.9% in controls (n = 17, P < 0.01). In animals receiving a second dose of MSCs, EF increased to 40.7 ± 3.1% by week 4, which was significantly higher than in the single-therapy group (EF 35.9 ± 1.8%, P < 0.05). Dual MSC treatment was also associated with greater myocardial mass and arteriolar density, with trends toward reduced myocardial fibrosis. These incremental benefits were especially observed in remote (non-infarct) segments of LV myocardium. Repeated stem cell intervention in both the acute and the sub-acute period after MI provides additional improvement in ventricular function beyond solitary cell dosing, largely owing to beneficial changes remote to the area of infarction.
Publisher: AME Publishing Company
Date: 08-2016
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.CARDFAIL.2013.03.011
Abstract: Although mesenchymal stem/stromal cells (MSC) have shown therapeutic promise after myocardial infarction (MI), the impact of cell dose and timing of intervention remains uncertain. We compared immediate and deferred administration of 2 doses of MSC in a rat model of MI. Sprague-Dawley rats were used. Allogeneic prospectively isolated MSC ("low" dose 1 × 10(6) or "high" dose 2 × 10(6) cells) were delivered by transepicardial injection immediately after MI ("early-low," "early-high"), or 1 week later ("late-low," "late-high"). Control subjects received cryopreservant solution alone. Left ventricular dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance. All 4 MSC-treatment cohorts demonstrated higher EF than control animals 4 weeks after MI (P values <.01 to <.0001), with function most preserved in the early-high group (absolute reduction in EF from baseline: control 39.1 ± 1.7%, early-low 26.5 ± 3.2%, early-high 7.9 ± 2.6%, late-low 19.6 ± 3.5%, late-high 17.9 ± 4.0%). Cell treatment also attenuated left ventricular dilatation and fibrosis and augmented left ventricular mass, systolic wall thickening (SWT), and microvascular density. Although early intervention selectively increased SWT and vascular density in the infarct territory, delayed treatment caused greater benefit in remote (noninfarct) myocardium. All outcomes demonstrated dose dependence for early MSC treatment, but not for later cell administration. The nature and magnitude of benefit from MSC after acute MI is strongly influenced by timing of cell delivery, with dose dependence most evident for early intervention. These novel insights have potential implications for cell therapy after MI in human patients.
Publisher: Wiley
Date: 08-2017
DOI: 10.1111/IMJ.13451
Abstract: Over the past quarter century, clinical trials have consistently demonstrated that lowering levels of low-density lipoprotein cholesterol (LDL-C) with statins reduces the rate of major adverse cardiovascular events. However, the findings that many patients continue to experience events or harbour inappropriately high LDL-C levels despite intensive statin therapy and the clinical reality of statin intolerance suggests that additional therapeutic strategies are required in order to achieve more effective reductions in cardiovascular risk. The emergence of inhibitory monoclonal antibodies targeted against proprotein convertase subtilisin kexin type 9 (PCSK9) provides a novel approach to reducing LDL-C levels. The current experience of PCSK9 inhibitors and implications for clinical use and cost effectiveness will be reviewed.
Publisher: Wiley
Date: 05-2007
Publisher: AME Publishing Company
Date: 08-2019
Publisher: AME Publishing Company
Date: 04-2020
Publisher: American Chemical Society (ACS)
Date: 27-09-2017
Publisher: Elsevier BV
Date: 04-2017
Publisher: Springer International Publishing
Date: 2022
Publisher: Springer International Publishing
Date: 2022
Publisher: Oxford University Press (OUP)
Date: 24-02-2021
DOI: 10.1093/EURHEARTJ/EHAB116
Abstract: Peripheral artery disease (PAD) revascularization can be performed by either endovascular or open surgical approach. Despite increasing use of endovascular revascularization, it is still uncertain which strategy yields better long-term outcomes. This retrospective cohort study evaluated patients hospitalized with PAD in Australia and New Zealand who underwent either endovascular or surgical revascularization between 2008 and 2015, and compared procedures using a propensity score-matched analysis. Hybrid interventions were excluded. The primary endpoint was mortality or major adverse limb events (MALE), defined as a composite endpoint of acute limb ischaemia, urgent surgical or endovascular reintervention, or major utation, up to 8 years post-hospitalization using time-to-event analyses 75 189 patients fulfilled eligibility (15 239 surgery and 59 950 endovascular), from whom 14 339 matched pairs (mean ± SD age 71 ± 12 years, 73% male) with good covariate balance were identified. Endovascular revascularization was associated with an increase in combined MALE or mortality [hazard ratio (HR) 1.13, 95% confidence interval (CI): 1.09–1.17, P & 0.001]. There was a similar risk of MALE (HR 1.04, 95% CI: 0.99–1.10, P = 0.15), and all-cause urgent rehospitalizations (HR 1.01, 95% CI: 0.98–1.04, P = 0.57), but higher mortality (HR 1.16, 95% CI: 1.11–1.21, P & 0.001) when endovascular repair was compared to surgery. In subgroup analysis, these findings were consistent for both claudication and chronic limb-threatening ischaemia presentations. Although the long-term risk of MALE was comparable for both approaches, enduring advantages of surgical revascularization included lower long-term mortality. This is at odds with some prior PAD studies and highlights contention in this space.
Location: Australia
No related grants have been discovered for Peter Psaltis.