ORCID Profile
0000-0003-2539-8038
Current Organisations
The University of Newcastle
,
Hunter New England Local Health District
,
John Hunter Hospital
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Publisher: Elsevier BV
Date: 02-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2023
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2023
DOI: 10.1101/2023.02.22.23286327
Abstract: To examine the delivery of patient-centred care and identify any gaps in care perceived as essential by patients this study examined outpatients’: 1) views on what characterises essential care and 2) experiences of care received, in relation to cardiac catheterisation and subsequent cardiovascular procedures. A cross-sectional descriptive study was undertaken. Surveys were posted to outpatients who had undergone elective cardiac catheterisation in the prior six months at an Australian tertiary public hospital. Participants completed a 65-item survey to determine: a) aspects of care they perceive as essential for a healthcare team to provide to patients receiving care for a cardiac condition (Important Care Survey) or b) their actual care received (Actual Care Survey). Numbers and percentages were used to calculate the most frequently identified essential care items by patients and the experiences of care received. Items rated as either ‘Essential’ or ‘Very important’ by at least 80% of participants were determined, reflecting patient endorsement of the importance of the component of care. A gap in patient-centred care was identified as being any item that was endorsed as essential/very important by 80% or more of participants but reported as received by less than 80% of participants. Of 582 eligible patients, 264 (45%) returned a completed survey. 43/65 items were endorsed by over 80% of participants as essential/very important. Of those, for 22 items, less than 80% of respondents reported the care as received. Gaps were identified in relation to GP consultation (3 items), preparation (4 items), having the procedure (2 items), follow-up care (1 item), subsequent decision making for treatment (4 items), prognosis (6 items) and post-treatment follow-up (1 item). Areas were identified where actual care fell short of patients’ perceptions of essential care, particularly general practitioner involvement, the referral process and information on patient prognosis.
Publisher: Elsevier BV
Date: 06-2019
Publisher: MDPI AG
Date: 18-08-2020
DOI: 10.3390/JCM9082664
Abstract: Background: Bevacizumab, a vascular endothelial growth factor (VEGF) monoclonal antibody commonly used for the treatment of various cancers, is often associated with adverse cardiovascular effects such as hypertension, cardiac and cerebral ischemia, thrombosis, and bleeding events. Factors associated with increased risks of adverse cardiovascular effects with bevacizumab have not been intensively studied. In this study, we determined factors associated with hospital admissions due to cardiovascular complications in patients who received bevacizumab for cancer treatment. Methods and Results: We retrospectively collected data for all patients treated with bevacizumab between the 1st January 2016 and the 31st December 2017 at the Hunter New England Local Health District. Patients’ characteristics and their medical history were obtained from hospital electronic medical records. Outcome data were sourced from the Institutional Cardiac and Stroke Outcomes Unit database. A total of n = 230 patients (mean age 65, males n = 124 (53.9%)) were treated with bevacizumab during the study period. N = 28 patients were admitted to hospital for a major cardiovascular-related event. Higher total treatment dose (p 0.05), concomitant hypertension (p = 0.005), diabetes (p = 0.04), atrial fibrillation (p = 0.03), and lack of use of statin therapy (p = 0.03) were key contributors to hospital admission. Conclusions: Results of our study highlight the fact that patients with concomitant baseline cardiovascular disease/risk factors are at an increased risk of cardiovascular hospitalization related to bevacizumab treatment. Careful baseline cardiovascular assessment may be an essential step to minimize cardiovascular complications.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2023
DOI: 10.1161/HYPERTENSIONAHA.122.17947
Abstract: Cardiovascular disease and cancer are 2 of the leading causes of death worldwide. Although improvements in outcomes have been noted for both disease entities, the success of cancer therapies has come at the cost of at times very impactful adverse events such as cardiovascular events. Hypertension has been noted as both, a side effect as well as a risk factor for the cardiotoxicity of cancer therapies. Some of these dynamics are in keeping with the role of hypertension as a cardiovascular risk factor not only for heart failure, but also for the development of coronary and cerebrovascular disease, and kidney disease and its association with a higher morbidity and mortality overall. Other aspects such as the molecular mechanisms underlying the lification of acute and long-term cardiotoxicity risk of anthracyclines and increase in blood pressure with various cancer therapeutics remain to be elucidated. In this review, we cover the latest clinical data regarding the risk of hypertension across a spectrum of novel anticancer therapies as well as the underlying known or postulated pathophysiological mechanisms. Furthermore, we review the acute and long-term implications for the lification of the development of cardiotoxicity with drugs not commonly associated with hypertension such as anthracyclines. An outline of management strategies, including pharmacological and lifestyle interventions as well as models of care aimed to facilitate early detection and more timely management of hypertension in patients with cancer and survivors concludes this review, which overall aims to improve both cardiovascular and cancer-specific outcomes.
Publisher: Oxford University Press (OUP)
Date: 06-07-2012
Abstract: Aortic valve stenosis (AS) and its precursor, aortic valve sclerosis (ASc), occur frequently in Western populations. Investigations to retard the progression of AS using statins have been unsuccessful. Development of ASc in humans is associated with increased aortic valve backscatter (AVBS) and poor tissue nitric oxide (NO) responsiveness. In an animal model, ramipril retarded AS/ASc development. We have now set out to identify factors associated with the progression of ASc in humans. At baseline and after 4 years, 204 randomly selected subjects (age 63 ± 6 years at study entry) underwent echocardiography with the determination of AVBS values, measurements of platelet NO responsiveness, plasma asymmetric dimethylarginine concentrations, lipid profile, high-sensitivity-C-reactive protein, routine biochemistry, and 25-hydroxy-vitamin D levels. During the study period, 68% of subjects had detectable AVBS progression. On multivariate analysis, higher calcium concentrations (β = 0.22 P = 0.004), poor platelet NO responsiveness (β = 0.18 P = 0.018), and increased arterial stiffness (β = 0.15 P = 0.044) were independent predictors of disease progression. The use of angiotensin-converting enzyme-inhibitors/angiotensin II receptor blockers (ACE-I/ARB) predicted the lack of disease progression (assessed categorically) in the overall cohort and in those without ASc at baseline (n = 159) (β = 0.8 P = 0.025 and β = 1.3 P = 0.001, respectively). No conventional coronary risk factors were associated with disease progression. This study of early aortic valve disease (i) demonstrates that disease progression occurs in the majority of the normal ageing population over a 4-year period (ii) provides evidence of the importance of the NO signalling cascade in disease development and progression and (iii) provides additional data linking ACE-I/ARB use with the retardation of ASc.
Publisher: Springer Science and Business Media LLC
Date: 08-2014
DOI: 10.1007/S10557-014-6538-5
Abstract: The thioredoxin system, which consists of thioredoxin (Trx), nicotinamide adenine dinucleotide phosphate (NADPH) and thioredoxin reductase (TrxR), has emerged as a major anti-oxidant involved in the maintenance of cellular physiology and survival. Dysregulation in this system has been associated with metabolic, cardiovascular, and malignant disorders. Thioredoxin-interacting protein (TXNIP), also known as vitamin D-upregulated protein or thioredoxin-binding-protein-2, functions as a physiological inhibitor of Trx, and pathological suppression of Trx by TXNIP has been demonstrated in diabetes and cardiovascular diseases. Furthermore, TXNIP effects are partially Trx-independent these include direct activation of inflammation and inhibition of glucose uptake. Many of the effects of TXNIP are initiated by its dissociation from intra-nuclear binding with Trx or other SH-containing proteins: these effects include its migration to cytoplasm, modulating stress responses in mitochondria and endoplasmic reticulum, and also potentially activating apoptotic pathways. TXNIP also interacts with the nitric oxide (NO) signaling system, with apparent suppression of NO effect. TXNIP production is modulated by redox stress, glucose levels, hypoxia and several inflammatory activators. In recent studies, it has been shown that therapeutic agents including insulin, metformin, angiotensin converting enzyme inhibitors and calcium channel blockers reduce TXNIP expression, although it is uncertain to what extent TXNIP suppression contributes to their clinical efficacy. This review addresses the role of TXNIP in health and in cardiovascular and metabolic disorders. Finally, the potential advantages (and disadvantages) of pharmacological suppression of TXNIP in cardiovascular disease and diabetes are summarized.
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.AMJMED.2012.12.015
Abstract: The objective of this study was to compare the impact of aging on nitric oxide (NO) modulation of platelet and vascular function in healthy women and women with polycystic ovary syndrome. A case-control study of women ages 18 to 60 years, comparing women with polycystic ovarian syndrome against age-matched healthy controls, was performed. A total of 242 women, of whom 109 had polycystic ovarian syndrome (based on Rotterdam criteria), participated in the study. Women who were pregnant or on clopidogrel were excluded from the study. Inhibition of platelet aggregation by nitric oxide (primary outcome measure), vascular endothelial function, plasma concentrations of N(G), N(G)-dimethyl-L-arginine (ADMA), endothelial progenitor cell count, and high-sensitivity C-reactive protein (markers of endothelial dysfunction and inflammation) were assessed. With increasing age in control women, there was progressive attenuation of platelet responses to NO, impairment of endothelial function, and elevation of ADMA levels (P ≤.001). Irrespective of age, women with polycystic ovarian syndrome exhibited greater impairment of all these parameters (all P <.05, 2-way analysis of variance) and demonstrated these anomalies earlier in life. Normal aging in women is associated with attenuation of NO-based signaling in platelets and blood vessels. In women with polycystic ovarian syndrome, these changes are present from early adult life and may contribute to premature atherogenesis.
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.IJCARD.2010.02.024
Abstract: The presence of aortic sclerosis has been associated with increased LV mass, particularly in hypertensive subjects. However, aortic sclerosis has also been associated with endothelial dysfunction, which may provide stimuli for development of left ventricular hypertrophy independent of afterload. Thus, we have sought to determine whether aortic sclerosis is a determinant of increased left ventricular mass in a non-hypertensive cohort of aging subjects. 79 subjects, mean age 68 ± 6 years, without existing cardiovascular disease or previous antihypertensive therapy were studied. LV volumes were calculated from the short axis stack of cardiac MRI and LV mass was indexed to height(2.7). The presence of aortic sclerosis was assessed with echocardiography using backscatter from the aortic valve (AV(BS)) and visual scoring. Plasma asymmetric dimethylarginine levels and vascular responses to salbutamol were used to assess endothelial function. ANCOVA was used to test the relationship between LV mass index and afterload. Univariate and multivariate analyses were performed to find determinants of increased LV mass. 15 (19%) of subjects had aortic sclerosis on the basis of AV(BS) none had aortic valve areas <1.5 cm(2). There was no significant difference in LV mass between subjects with and without aortic sclerosis. While LV mass was directly related to systolic blood pressure, this relationship was independent of the presence/absence of aortic sclerosis. On multivariate analysis, significant correlates of increased LV mass were male gender, systolic blood pressure and increased BMI, but not presence of aortic sclerosis. In this aging normotensive population free of established cardiovascular disease, aortic sclerosis is not associated with left ventricular hypertrophy.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2010
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/8254590
Publisher: American Physiological Society
Date: 02-2019
DOI: 10.1152/AJPENDO.00227.2018
Abstract: Obesity, particularly visceral adiposity, has been linked to mitochondrial dysfunction and increased oxidative stress, which have been suggested as mechanisms of insulin resistance. The mechanism(s) behind this remains incompletely understood. In this study, we hypothesized that mitochondrial complex II dysfunction plays a role in impaired insulin sensitivity in visceral adipose tissue of subjects with obesity. We obtained subcutaneous and visceral adipose tissue biopsies from 43 subjects with obesity (body mass index ≥ 30 kg/m 2 ) during planned bariatric surgery. Compared with subcutaneous adipose tissue, visceral adipose tissue exhibited decreased complex II activity, which was restored with the reducing agent dithiothreitol (5 mM) ( P 0.01). A biotin switch assay identified that cysteine oxidative posttranslational modifications (OPTM) in complex II subunit A (succinate dehydrogenase A) were increased in visceral vs. subcutaneous fat ( P 0.05). Insulin treatment (100 nM) stimulated complex II activity in subcutaneous fat ( P 0.05). In contrast, insulin treatment of visceral fat led to a decrease in complex II activity ( P 0.01), which was restored with addition of the mitochondria-specific oxidant scavenger mito-TEMPO (10 µM). In a cohort of 10 subjects with severe obesity, surgical weight loss decreased OPTM and restored complex II activity, exclusively in the visceral depot. Mitochondrial complex II may be an unrecognized and novel mediator of insulin resistance associated with visceral adiposity. The activity of complex II is improved by weight loss, which may contribute to metabolic improvements associated with bariatric surgery.
Publisher: Wiley
Date: 16-05-2013
DOI: 10.1111/BPH.12152
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.AMJMED.2009.09.024
Abstract: Vitamin D deficiency is associated with significant increases in the incidence of cardiovascular risk factors and mortality. However, the mechanisms underlying this association remain unclear. The current study evaluated the possible relationships among vitamin D status, endothelial dysfunction, and inflammation. Plasma concentrations of 25-hydroxyvitamin D(3) were determined by radioimmunoassay in a normal population cohort (n=253) aged 51 to 77 years (mean 63.4+/-6 years). Asymmetric dimethylarginine, a marker/mediator of endothelial dysfunction, was assayed by high-performance liquid chromatography. High-sensitivity C-reactive protein levels were used as a marker of inflammatory activation. On univariate analyses, low 25-hydroxyvitamin D(3) levels were inversely correlated with asymmetric dimethylarginine concentrations, high-sensitivity C-reactive protein levels, and body mass index. Seasonal fluctuations in 25-hydroxyvitamin D(3) levels were associated with reciprocal asymmetric dimethylarginine concentration fluctuations. Hypertension and treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker also were associated with low 25-hydroxyvitamin D(3) levels. On multiple linear analysis, both asymmetric dimethylarginine (beta=-0.19, P=.003) and high-sensitivity C-reactive protein (beta=-0.14, P=.03) concentrations were inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations other significant correlates were male gender (beta=0.19, P=.003), calcium levels (beta=0.14, P=.03), and use of angiotensin-converting enzyme inhibitor (beta=-0.17, P=.007). Low 25-hydroxyvitamin D(3) levels are associated with markers of endothelial dysfunction and inflammatory activation, representing potential mechanisms for incremental coronary risk.
Publisher: Elsevier BV
Date: 11-2016
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.EJPHAR.2008.05.051
Abstract: Understanding of the pathophysiology of aortic valve stenosis (AVS) and finding potentially effective treatments are impeded by the lack of suitable AVS animal models. A previous study demonstrated the development of AVS in rabbits with vitamin D(2) and cholesterol supplementation without any hemodynamic changes in the cholesterol supplemented group alone. The current study aimed to determine whether AVS develops in an animal model with vitamin D(2) supplementation alone, and to explore pathophysiological mechanisms underlying this process. The effects of 8 weeks' treatment with vitamin D(2) alone (n=8) at 25,000 IU/4 days weekly on aortic valve structure and function were examined in male New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)), transvalvular velocity, and transvalvular pressure gradient were utilized to quantitate changes in valve structure and function. Valvular histology/immunochemistry and function were examined after 8 weeks. Changes in valves were compared with those in endothelial function and in valvular measurement of thioredoxin-interacting protein (TXNIP), a marker/mediator of reactive oxygen species-induced oxidative stress. Vitamin D(2) treated rabbits developed AVS with increased AV(BS) (17.6+/-1.4 dB vs 6.7+/-0.8 dB, P<0.0001), increased transvalvular velocity and transvalvular pressure gradient (both P<0.01 via 2-way ANOVA) compared to the control group. There was associated valve calcification, lipid deposition and macrophage infiltration. Endothelial function was markedly impaired, and intravalvular TXNIP concentration increased. In this model, vitamin D(2) induces the development of AVS with histological features similar to those of early AVS in humans and associated endothelial dysfunction/redox stress. AVS development may result from the loss of nitric oxide suppression of TXNIP expression.
Publisher: Wiley
Date: 13-02-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2013
Publisher: Elsevier BV
Date: 03-0007
DOI: 10.1016/J.PHARMTHERA.2012.04.001
Abstract: Aortic valve stenosis (AS) is the most common form of valvular heart disease in the Western world, affecting ~40% of the population over the age of 80 to date the only established treatment is valve replacement. However, AS progression occurs over many years, and is associated from its earliest stages with increased risk of coronary events. Recent insight into the pathophysiology of AS has included central roles for angiotensin II, for diminished nitric oxide effect at the level of valve endothelium and matrix, and for inflammatory activation/redox stress culminating in activation of pro-calcific stimuli. Despite the presence of atheroma within the stenotic valve, hyperlipidemia per se does not play a critic role in the development of obstructive disease. We review emerging options for pharmacotherapy of AS, including in particular retardation of disease progression. The various clinical evaluations of lipid-reducing therapy have been uniformly unsuccessful in slowing AS progression. However, recent studies in animal models and retrospective evaluations in humans suggest that ACE inhibitors and/or angiotensin receptor blockers may be effective in this regard. Furthermore, agents normally utilized to treat osteoporosis also offer promise in retarding AS. Given the considerable morbidity, mortality and health care costs associated with AS, such therapeutic developments should be expedited.
Publisher: Elsevier BV
Date: 02-2015
Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2020
DOI: 10.1200/JGO.19.00088
Publisher: Springer Science and Business Media LLC
Date: 30-01-2008
DOI: 10.1007/S11936-008-0004-2
Abstract: The main components of the metabolic syndrome (MS) are abdominal obesity, atherogenic dyslipidemia, raised blood pressure, insulin resistance with or without glucose intolerance, and proinflammatory and prothrombotic states. The clustering of these metabolic risk factors significantly increases the risk of type 2 diabetes and promotes vascular endothelial dysfunction, inflammation, and increased oxidative stress. The net result is an increase in the risk of atherosclerotic cardiovascular disease. Therefore, management of MS is of utmost importance, especially considering its rapidly increasing prevalence in a population with rising obesity rates and its significant cardiovascular implications. The primary management of this syndrome involves the correction of the underlying risk factors--obesity, physical inactivity, and an atherogenic diet--with lifestyle modifications including increased physical activity and dietary modification. Smoking cessation also should be encouraged. However, pharmacologic therapies are often required to address cardiovascular risk factors. These agents can be categorized broadly into 1) anorectic agents, 2) insulin-sensitizing agents, 3) statins, and 4) renin-angiotensin system antagonists. Emerging therapies include adipokines, endocannabinoid inhibitors, and metabolic modulators, such as perhexiline and trimetazidine. To date, these therapies have not been shown to normalize the metabolic and cardiovascular burden of MS, and there still is no single therapeutic agent for its management.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.HLC.2022.09.017
Abstract: Australia's First Nations Peoples, Aboriginal and Torres Strait Islanders, have reduced life expectancy compared to the wider community. Cardiovascular diseases, mainly driven by ischaemic heart disease, are the leading contributors to this disparity. Despite over a third of First Nations Peoples living in New South Wales, the bulk of the peer-reviewed literature is from Central Australia and Far North Queensland. Regardless of the site of publication, First Nations Peoples are significantly younger at disease onset and have higher rates of comorbidities, in turn driving adverse health events. On top of this, very few First Nations Peoples specific cardiovascular interventions or programs have been shown to improve outcomes. The traditional biomedical model of care is less efficacious and non-traditional models of communication such as clinical yarning may benefit both clinicians and patients. The key purpose of this review is to highlight the deficiencies of our knowledge of cardiovascular burden of disease for First Nations Peoples and to serve as a catalyst for more dedicated research. We need to have relationships with communities and concentrate on community improvement and partnerships. By involving First Nations Peoples researchers in collaboration with local communities in all levels of health care design and intervention will improve outcomes.
Publisher: BMJ
Date: 11-2022
DOI: 10.1136/OPENHRT-2022-002096
Abstract: Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is now the standard of care, but whether the demonstrated benefits of RM translate into improvements in heart failure (HF) management is controversial. This systematic review addresses the role of RM in patients with HF with a CIED. A systematic search of the literature for randomised clinical trials in patients with HF and a CIED assessing efficacy/effectiveness of RM was performed using MEDLINE, PubMed and Embase. Meta-analysis was performed on the effects of RM of CIEDs in patients with HF on mortality and readmissions. Effects on implantable cardiac defibrillator (ICD) therapy, healthcare costs and clinic presentations were also assessed. 607 articles were identified and refined to 10 studies with a total of 6579 patients. Implementation of RM was not uniform with substantial variation in methodology across the studies. There was no reduction in mortality or hospital readmission rates, while ICD therapy findings were inconsistent. There was a reduction in patient-associated healthcare costs and reduction in healthcare presentations. RM for patients with CIEDs and HF was not uniformly performed. As currently implemented, RM does not provide a benefit on overall mortality or the key metric of HF readmission. It does provide a reduction in healthcare costs and healthcare presentations. CRD42019129270.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.PHRS.2009.06.006
Abstract: A number of previous investigators have demonstrated that arterial augmentation index (AIx), a measure of apparent arterial stiffness, reflects in part vascular endothelial function, and that AIx is modulated by nitric oxide (NO) responses. We evaluated AIx in a population of 253 ageing subjects (mean age 63.4+/-6 (standard deviation, SD) years) and its relationship to (i) plasma levels of asymmetric dimethylarginine (ADMA), a marker and mediator of vascular endothelial dysfunction and (ii) the ratio of ADMA to its non-metabolised enantiomer symmetric dimethylarginine (SDMA), an inverse index of ADMA metabolic clearance. Evaluation was performed by univariate followed by multivariate analyses. On multivariate analyses, both ADMA (beta=0.16, p=0.01) and ADMA:SDMA (beta=0.21, p<0.001) ratio were significant direct correlates of AIx. Other significant correlates of AIx on multivariate analysis were: use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEi/ARB) (beta=-0.24, p=0.004), smoking history (beta=0.15, p=0.007), male gender (beta=-0.38, p<0.001), creatinine clearance (CrCL) (beta=-0.25, p<0.001), and history of hypertension (beta=0.17, p=0.04). We conclude that (1) endothelial dysfunction engendered by impairment of NO synthesis may represent the basis for increased arterial stiffness in ageing in iduals and (2) the fundamental biochemical anomaly may be impairment of ADMA clearance. These pathophysiological factors are likely to be relevant to optimize therapy to ameliorate disorders of arterial compliance in the ageing population.
Publisher: Mary Ann Liebert Inc
Date: 09-2019
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.NIOX.2011.04.009
Abstract: Nitric oxide (NO) is a modulator of left ventricular hypertrophy (LVH) and myocardial relaxation. The impact of NO availability on development of LVH has never been demonstrated in humans. We tested the hypotheses that elevation of asymmetric dimethylarginine (ADMA) concentrations (biochemical marker of decreased NO generation), and impairment of vascular responsiveness to NO donor GTN, would each predict the presence of LVH and associated LV diastolic dysfunction in a normal aging population. In 74 subjects aged 68±6 years, LV volumes and mass indexed to height(2.7) (LVMI) were calculated from cardiac MRI. Despite the absence of clinically-defined LVH, there was a relationship (r=0.29 p=0.01) between systolic BP and LVMI. Both elevation of ADMA levels to the highest quartile or impairment of GTN responsiveness (determined by applanation tonometry) to the lowest quartile were determinants of LVMI independent of systolic BP (p=0.01 and p=0.03, respectively). Filling pressure (E/E' ratio from echocardiography) was increased in patients with impaired vascular NO responsiveness (p<0.05) irrespective of LVMI. ADMA remained a significant determinant of LVMI on multivariate analysis. These data imply that NO bioavailability within the myocardium modulates earliest stages of LVH development and facilitates development of diastolic dysfunction at a given LV mass.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
DOI: 10.1161/HYPERTENSIONAHA.119.14330
Abstract: Pulmonary hypertension (PH) due to left heart disease (LHD) is the most common type of PH and is defined as mean pulmonary artery systolic pressure of mm Hg and pulmonary capillary wedge pressure mm Hg during right heart catheterization. LHD may lead to elevated left atrial pressure alone, which in the absence of intrinsic pulmonary vascular disease will result in PH without changes in pulmonary vascular resistance. Persistent elevation in left atrial pressure may, however, also be associated with subsequent pulmonary vascular remodeling, vasoconstriction, and an increase in pulmonary vascular resistance. Hence, there are 2 subgroups of PH due to LHD, isolated postcapillary PH and combined post- and precapillary PH, with these groups have differing clinical implications. Differentiation of pulmonary arterial hypertension and PH due to LHD is critical to guide management planning however, this may be challenging. Older patients, patients with metabolic syndrome, and patients with imaging and clinical features consistent with left ventricular dysfunction are suggestive of LHD etiology rather than pulmonary arterial hypertension. Hemodynamic measures such as diastolic pressure gradient, transpulmonary gradient, and pulmonary vascular resistance may assist to differentiate pre- from postcapillary PH and offer prognostic insights. However, these are influenced by fluid status and heart failure treatment. Pulmonary arterial hypertension therapies have been trialed in the treatment with concerning results reflecting disease heterogeneity, variation in inclusion criteria, and mixed end point criteria. The aim of this review is to provide an updated definition, discuss possible pathophysiology, clinical aspects, and the available treatment options for PH due to LHD.
Publisher: MDPI AG
Date: 22-05-2023
Abstract: Obesity is associated with significant metabolic co-morbidities, such as diabetes, hypertension, and dyslipidaemia, as well as a range of cardiovascular diseases, all of which lead to increased hospitalisations, morbidity, and mortality. Adipose tissue dysfunction caused by chronic nutrient stress can result in oxidative stress, mitochondrial dysfunction, inflammation, hypoxia, and insulin resistance. Thus, we hypothesised that reducing adipose tissue oxidative stress via adipose tissue-targeted overexpression of the antioxidant mitochondrial catalase (mCAT) may improve systemic metabolic function. We crossed mCAT (floxed) and Adipoq-Cre mice to generate mice overexpressing catalase with a mitochondrial targeting sequence predominantly in adipose tissue, designated AdipoQ-mCAT. Under normal diet conditions, the AdipoQ-mCAT transgenic mice demonstrated increased weight gain, adipocyte remodelling, and metabolic dysfunction compared to the wild-type mice. Under obesogenic dietary conditions (16 weeks of high fat/high sucrose feeding), the AdipoQ-mCAT mice did not result in incremental impairment of adipose structure and function but in fact, were protected from further metabolic impairment compared to the obese wild-type mice. While AdipoQ-mCAT overexpression was unable to improve systemic metabolic function per se, our results highlight the critical role of physiological H2O2 signalling in metabolism and adipose tissue function.
Publisher: Georg Thieme Verlag KG
Date: 31-08-2014
Abstract: The nitric oxide (NO)/soluble guanylate cyclase (sGC) system is fundamental to endothelial control of vascular tone, but also plays a major role in the negative modulation of platelet aggregation. The phenomenon of platelet NO resistance, or decreased antiaggregatory response to NO, occurs increasingly with advanced age, as well as in the context of cardiovascular disease states such as heart failure, ischemic heart disease, and aortic valve disease. The central causes of NO resistance are "scavenging" of NO and dysfunction of sGC. In the current review, we discuss the roles of several modulators of NO synthesis and of the NO/sGC cascade on changes in platelet physiology with aging, together with potential therapeutic options to reduce associated thrombotic risk.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-04-2019
Abstract: Obesity is a precursor to heart failure with preserved ejection fraction. Biomarkers that identify preclinical metabolic heart disease ( MHD ) in young obese patients would help identify high‐risk in iduals for heart failure prevention strategies. We assessed the predictive value of GAL3 (galectin–3), FSTL3 (follistatin‐like 3 peptide), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) to identify stage B MHD in young obese participants free of clinically evident cardiovascular disease. Asymptomatic obese patients (n=250) and non‐obese controls (n=21) underwent echocardiographic cardiac phenotyping. Obese patients were classified as MHD positive ( MHD ‐ POS n=94) if they had abnormal diastolic function or left ventricular hypertrophy and had estimated pulmonary artery systolic pressure ≥35 mm Hg. Obese patients without such abnormalities were classified as MHD negative (MHD‐NEG n=52). Serum biomarkers timed with echocardiography. MHD ‐ POS and MHD‐NEG in iduals were similarly obese, but MHD ‐ POS patients were older, with more diabetes mellitus and metabolic syndrome. Right ventricular coupling was worse in MHD ‐ POS patients ( P .001). GAL 3 levels were higher in MHD ‐ POS versus MHD ‐NEG patients (7.7±2.3 versus 6.3±1.9 ng/mL, respectively P .001). Both GAL 3 and FSTL 3 levels correlated with diastolic dysfunction and increased pulmonary artery systolic pressure but not with left ventricular mass. In multivariate models including all 3 biomarkers, only GAL 3 remained associated with MHD (odds ratio: 1.30 95% CI , 1.01–1.68 P =0.04). In young obese in iduals without known cardiovascular disease, GAL 3 is associated with the presence of preclinical MHD . GAL 3 may be useful in screening for preclinical MHD and identifying in iduals with increased risk of progression to obesity‐related heart failure with preserved ejection fraction.
Publisher: Wiley
Date: 28-06-2019
DOI: 10.1111/AJCO.13179
Abstract: Ibrutinib increases the risk of atrial fibrillation (AF) and is associated with bleeding tendencies. Reported rates of arrhythmia are variable in different studies. The aim of the current analysis was to evaluate the incidence of AF in a single-center cohort of patients. This analysis was conducted at Hunter New England Local Health District, Australia between April 1, 2015 and June 30, 2017. We included all consecutive patients commenced on ibrutinib for hematological malignancies. Patients with a history of paroxysmal AF were excluded. The primary end point was incidence of AF. Time to diagnosis and management were secondary outcomes of interest. A total of 24 patients (age 73 ± 9 years, males n = 16 [67%]) were commenced on ibrutinib treatment during the study period with chronic lymphocytic leukemia (n = 21, 88%) as the main indication. During a median follow-up of 12 months, four (17%) patients were diagnosed with AF with increasing age, duration of ibrutinib treatment as associations. The median time to AF diagnosis was 9 (interquartile range [IQR]: 7-18) months. All patients were managed with a rate control strategy with beta blockers as the preferred agents. Three (75%) patients were commenced on anticoagulation for stroke prevention. During a follow-up of 18 (IQR: 17-23) months following AF onset, one patient required hospitalization for AF. There were no bleeding complications reported. In conclusion, this series noted a higher incidence of AF than previously reported. Oncologists and cardiologists need to be aware of the increased risk of AF in patients receiving ibrutinib.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.JCMG.2009.03.016
Abstract: We sought to identify clinical, physiological, and biochemical correlates, including markers of endothelial dysfunction and of tissue nitric oxide (NO) responsiveness, of the presence of aortic sclerosis (ASc) in an aging population. Aortic sclerosis has been regarded predominantly as a precursor of hemodynamically significant aortic stenosis. However, ASc also represents an independent correlate of increased risk of cardiovascular morbidity and mortality the basis of this association is incompletely understood. The assumption that the pathogenesis of aortic valve disease is similar to that of atherosclerosis has not been supported by recent studies rather there has been increasing evidence of a pathogenetic role of inflammation and endothelial dysfunction. Furthermore, we have recently developed methodology for echocardiographic quantitation of early aortic valve disease. Randomly selected subjects (n = 253) ages 51 to 77 years underwent transthoracic echocardiography aortic valve ultrasonic backscatter score (AV(BS)) was used to quantitate echogenicity of the aortic valve. Conventional coronary risk factors were identified. Integrity of NO generation/response was assessed via: 1) plasma asymmetric dimethylarginine concentrations, as a marker of endothelial dysfunction 2) inhibition of platelet aggregation by the NO donor sodium nitroprusside, as a measure of tissue NO responsiveness and also a coronary prognostic marker and 3) aortic augmentation index, as a measure of arterial stiffness/wave reflection. All putative correlations with AV(BS) were examined by univariate and multiple linear regression analyses. On the basis of AV(BS) scores, ASc was present in 19.4% of subjects. The AV(BS) directly correlated with patients' age but inversely correlated with high-sensitivity C-reactive protein, creatinine clearance, and platelet NO responsiveness. On multiple linear regression, ASc was associated with impaired platelet NO responsiveness (beta = -0.16, p = 0.02), advancing age (beta = 0.21, p = 0.003), and low body mass index (beta = -0.23, p = 0.001). Aortic sclerosis is associated with platelet NO resistance rather than conventional coronary risk factors: this might explain the increased thrombotic risk in ASc.
Publisher: Springer Science and Business Media LLC
Date: 31-05-2014
DOI: 10.1007/S12350-014-9901-9
Abstract: FDG PET/CT with myocardial perfusion imaging is a useful method for evaluating cardiac sarcoidosis (CS), but interpretation is not standardized. We developed a method for quantification of cardiac FDG PET/CT and evaluated its relationship to conventional interpretation, perfusion defects, clinical events, and immunosuppressive treatment. FDG PET/CT with MPI studies performed for CS (n = 38) were retrospectively compared to negative control studies acquired for oncologic indications (n = 10). Quantitative measures of FDG volume-intensity (Cardiac Metabolic Activity, CMA) was performed using standardized uptake values (SUVs). CMA (477.7 ± 909 vs 0.55 ± 2.1 vs 0.3 ± 0.3 g glucose, P = .02) was significantly greater in visually FDG-positive studies compared to visually negative and oncologic negative studies. Among patients with CS, CMA was greater in studies with an EF < 50% (760.3 ± 1,148 vs 87.4 ± 161 g glucose, P = .03) and preceding an adverse clinical event (1,095 ± 1,253 vs 73 ± 144 g glucose, P = .006). CMA was the only independent predictor of events by multivariate analysis. In patients with repeat examinations (n = 7), CMA decreased with prednisone treatment in 5 of 6 patients. Quantification of FDG uptake in CS correlates with lower EFs, clinical events, and immunosuppression treatment.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.NIOX.2011.06.005
Abstract: Polycystic ovary syndrome (PCOS) is associated with incremental risk of atherosclerosis and possibly of cardiovascular events. Insulin resistance (IR) occurs frequently in PCOS subjects, which might be one of the mechanisms involved in engendering such risk. We sought to evaluate whether the impact of other factors potentially associated both with PCOS and with IR might differentially modulate degree of IR in women with and without PCOS. We measured body mass index (BMI), hs-CRP, plasma concentrations of asymmetric dimethylarginine (ADMA), vitamin D (25(OH)D3) levels and platelet responsiveness to nitric oxide donor sodium nitroprusside (NO responsiveness) in 47 young women (n=27 with PCOS and n=20 weight-matched controls) without metabolic syndrome, hypertension or overt cardiovascular disease. We performed univariate and multivariate regression analyses to establish correlates of the quantitative insulin-sensitivity check index (QUICKI), as a marker of IR. On univariate analysis, plasma 25(OH)D3 levels and low NO responsiveness tended to be direct correlates with QUICKI in the entire subject group. BMI, hs-CRP, and ADMA levels were significant inverse correlates of QUICKI in PCOS subjects, but not in subjects without PCOS. On multivariate analysis, NO responsiveness, and 25(OH)D3 levels, but not PCOS per se were significant correlates of QUICKI. In the entire cohort of young women, low NO responsiveness and vitamin D deficiency are associated with low QUICKI, while elevated ADMA, inflammatory activation and obesity are selectively associated with low QUICKI in PCOS subjects this may contribute to the increased cardiovascular risk associated with this syndrome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-01-2016
Abstract: Myocardial hypertrophy and dysfunction are key features of metabolic heart disease due to dietary excess. Metabolic heart disease manifests primarily as diastolic dysfunction but may progress to systolic dysfunction, although the mechanism is poorly understood. Liver kinase B1 ( LKB 1) is a key activator of AMP ‐activated protein kinase and possibly other signaling pathways that oppose myocardial hypertrophy and failure. We hypothesized that LKB 1 is essential to the heart's ability to withstand the metabolic stress of dietary excess. Mice heterozygous for cardiac LKB 1 were fed a control diet or a high‐fat, high‐sucrose diet for 4 months. On the control diet, cardiac LKB 1 hearts had normal structure and function. After 4 months of the high‐fat, high‐sucrose diet, there was left ventricular hypertrophy and diastolic dysfunction in wild‐type mice. In cardiac LKB 1 (versus wild‐type) mice, high‐fat, high‐sucrose feeding caused more hypertrophy (619 versus 553 μm 2 , P .05), the de novo appearance of systolic dysfunction (left ventricular ejection fraction 41% versus 59%, P .01) with left ventricular dilation (3.6 versus 3.2 mm, P .05), and more severe diastolic dysfunction with progression to a restrictive filling pattern (E/A ratio 5.5 versus 1.3, P =0.05). Myocardial dysfunction in hearts of cardiac LKB 1 mice fed the high‐fat, high‐sucrose diet was associated with evidence of increased apoptosis and apoptotic signaling via caspase 3 and p53/ PUMA (p53 upregulated modulator of apoptosis) and more severe mitochondrial dysfunction. Partial deficiency of cardiac LKB 1 promotes the adverse effects of a high‐fat, high‐sucrose diet on the myocardium, leading to worsening of diastolic function and the de novo appearance of systolic dysfunction. LKB 1 plays a key role in protecting the heart from the consequences of metabolic stress.
Publisher: Springer Science and Business Media LLC
Date: 07-08-2013
DOI: 10.1007/S10557-013-6481-X
Abstract: Little information is available concerning the mechanism(s) underlying Takotsubo cardiomyopathy (TTC), other than evidence of associated catecholamine secretion. Given the known effects of catecholamines on endothelial function, we tested the hypothesis that TTC might also be associated with impairment of nitric oxide (NO) signaling. We now report an evaluation of NO signaling in TTC patients (vs. aged-matched controls) in relation to (a) severity of the acute attack and (b) rate of recovery. In 56 patients with TTC, we utilized (1) platelet responsiveness to NO and (2) plasma levels of asymmetric dimethylarginine (ADMA) as indices of integrity of the cyclic guanosine monophosphate (cGMP) pathway. Additionally, endothelial progenitor cell (EPC) counts, which are partially NO-dependent, were evaluated. These parameters were measured at the time of diagnosis and 3 months thereafter, and compared with an aging female cohort (n = 81). The data suggested that both NO generation and effect were accentuated in TTC patients: ADMA concentrations were lower (p = 0.003), and responsiveness to NO substantially greater (p = 0.0001) than in controls both acutely and after 3 months. Markers of severity of TTC attacks directly correlated with NO responsiveness, while extent of recovery at 3 months varied inversely with ADMA concentrations. TTC is associated with intensification of NO signaling relative to that in normal age-matched females. Our data are consistent with this intensified signal's potential contribution to the extent of initial myocardial injury, but conversely to accelerated recovery.
Publisher: SAGE Publications
Date: 29-05-2018
Abstract: Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass graft (CABG) surgery. This arrhythmia occurs more frequently among patients who receive perioperative inotropic therapy (PINOT). Administration of nitrates with antiplatelet agents reduces the conversion rate of cyclic guanosine monophosphate to guanosine monophosphate. This process is associated with increased concentrations of free radicals, catecholamines, and blood plasma volume. We hypothesized that patients undergoing CABG surgery who receive PINOT may be more susceptible to POAF when nitrates are administered with antiplatelet agents. Clinical records were examined from a prospectively maintained cohort of 4,124 patients undergoing primary isolated CABG surgery to identify POAF-associated factors. POAF risk was increased among patients receiving PINOT, and the greatest effect was observed when nitrates were administered with antiplatelet therapy. Adjustment for comorbidities did not substantively change the study results. Administration of nitrates with certain antiplatelet agents was associated with an increased POAF risk among patients undergoing CABG surgery. Additional studies are needed to determine whether preventive strategies such as administration of antioxidants will reduce this risk.
Publisher: Elsevier BV
Date: 11-2016
Publisher: Wiley
Date: 30-01-2019
DOI: 10.1111/AJR.12456
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-08-2014
Abstract: Impaired generation and signaling of nitric oxide ( NO) contribute substantially to cardiovascular ( CV ) risk ( CVR ) associated with hypertension, hyperlipidemia, and diabetes mellitus. In our rapidly aging society, advanced age is, in itself, a consistent and independent CVR factor. Many processes involved in aging are modulated by NO . We therefore postulated that aging might be independently associated with impaired NO signaling. In a prospective cohort study of 204 subjects (mean age 63±6 at study entry), we evaluated the effects of 4 years of aging on parameters of NO generation and effect, including platelet aggregability and responsiveness to NO , and plasma concentrations of the NO synthase inhibitor, asymmetric dimethylarginine ( ADMA ). Clinical history, lipid profile, high‐sensitivity C‐reactive protein, routine biochemistry, and 25‐hydroxyvitamin D levels were obtained at study entry and after 4 years of follow‐up. Aging was associated with marked deterioration of responsiveness of platelets to NO ( P .0001) and increases in plasma ADMA concentrations ( P .0001). There was a significant correlation between changes in these parameters over time ( r =0.2 P =0.013). On multivariable analyses, the independent correlates of deterioration of responsiveness of platelets to NO were female gender (β=0.17 P =0.034) and low vitamin D concentrations (β=0.16 P =0.04), whereas increases in ADMA were associated with presence of diabetes (β=0.16 P =0.03) and impaired renal function (β=0.2 P =0.004). Aging is associated with marked impairment of determinants of NO generation and effect, to an extent which is commensurate with adverse impact on CV outcomes. This deterioration represents a potential target for therapeutic interventions.
Publisher: Informa UK Limited
Date: 02-2012
DOI: 10.1586/ERC.11.190
Abstract: Takotsubo cardiomyopathy (TTC) is a form of reversible acute cardiac dysfunction of uncertain pathogenesis, which occurs predominantly in postmenopausal women, often with antecedent severe stress. Systolic dysfunction most commonly affects the apex of the left ventricle. There is considerable uncertainty regarding the pathogenesis of TTC and the optimal diagnostic methodology. Acute catecholamine release may play a component role, but the regional hypokinesis is associated with an acute inflammatory process, with resultant early release of brain natriuretic peptide (BNP) and N-terminal pro-BNP. As the diagnosis of TTC has largely been a process of exclusion, there has been considerable underdiagnosis. The combination of demographics, preceding history, ECG appearances and N-terminal pro-BNP elevation may provide the basis for improved early diagnosis. Complete recovery takes at least several months, with a risk of recurrent episodes. Efforts to delineate pathogenesis, expedite diagnosis and evaluate residual disability may assist in the development of appropriate treatment regimens.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2008
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.IJCARD.2013.07.159
Abstract: Impaired tissue responsiveness to nitric oxide (NO) occurs in many cardiovascular diseases as well as with advanced age and is a correlate of poor outcomes. This phenomenon results from oxidative stress, with NO "scavenging" and dysfunction of soluble guanylate cyclase (sGC). Thioredoxin-interacting protein (TXNIP) is a major intracellular regulator of inflammatory activation and redox stress, but its interactions with NO/sGC are poorly understood. We have now evaluated the relationship between platelet TXNIP expression and function of the NO/sGC axis in subjects of varying age and during therapy with ramipril. Young (n=42) and aging (n=49) subjects underwent evaluation of platelet TXNIP content. Aging subjects additionally had measurements of platelet NO responsiveness and routine biochemistry. Platelet TXNIP content was greater (376±33 units) in the aging compared to younger subjects (289±13 units p<0.05). In the aging subjects there was a significant negative correlation (r=-0.50, p<0.001) between platelet TXNIP content and NO responsiveness. In a separate cohort of 15 subjects two week treatment with ramipril, which reversed platelet NO resistance and potentiated sGC activity, also decreased platelet TXNIP content by 40% (p=0.011). Platelet TXNIP content increases with aging, varies inversely with responsiveness to NO, and diminishes rapidly following treatment with ramipril. These data suggest that TXNIP-induced oxidative stress may be a critical modulator of tissue resistance to NO, a fundamental basis for cardiovascular disease. Analogously suppression of TXNIP expression can potentially be utilized as an index of restoration of cardiovascular homeostasis.
Publisher: Elsevier BV
Date: 03-2019
Publisher: BMJ
Date: 11-07-2012
DOI: 10.1136/HEARTJNL-2011-301481
Abstract: Tako-Tsubo cardiomyopathy (TTC) is associated with regional left ventricular dysfunction, independent of the presence of fixed coronary artery disease. Previous studies have used T2-weighted cardiac MRI to demonstrate the presence of periapical oedema. The authors sought to determine the distribution, resolution and correlates of oedema in TTC. 32 patients with TTC were evaluated at a median of 2 days after presentation, along with 10 age-matched female controls. Extent of oedema was quantified both regionally and globally scanning was repeated in patients with TTC after 3 months. Correlations were sought between oedema and the extent of hypokinesis, catecholamine release, release of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and markers of systemic inflammatory activation (high-sensitivity C-reactive protein and platelet response to nitric oxide). In the acute phase of TTC, T2-weighted signal intensity was greater at the apex than at the base (p<0.0001) but was nevertheless significantly elevated at the base (p<0.0001), relative to control values. Over 3 months, T2-weighted signal decreased substantially, but remained abnormally elevated (p<0.02). The regional extent of oedema correlated inversely with radial myocardial strain (except at the apex). There were also direct correlations between global T2-weighted signal and (1) plasma normetanephrine (r=0.39, p=0.04) and (2) peak NT-proBNP (r=0.39, p=0.03), but not with systemic inflammatory markers. TTC is associated with slowly resolving global myocardial oedema, the acute extent of which correlates with regional contractile disturbance and acute release of both catecholamines and NT-proBNP.
Publisher: Springer Science and Business Media LLC
Date: 04-2010
DOI: 10.1007/S10557-010-6233-0
Abstract: The A-HeFT trial demonstrated incremental survival with hydralazine/isosorbide dinitrate combination in African-American patients with chronic heart failure (CHF). It has been suggested that hydralazine might enhance nitric oxide (NO)-mediated effects of organic nitrates by decreasing superoxide (O (2) (-) ) formation, one of the factors inducing NO resistance. We evaluated whether hydralazine therapy potentiates nitrate-induced vasodilation and inhibition of platelet aggregation by ameliorating NO resistance. Patients (n = 14) with NYHA class II-III CHF were studied in a randomised, double-blind, placebo-controlled, crossover study of the effects of hydralazine therapy (25 mg b.d., for 1 week) on physiological responsiveness to glyceryl trinitrate (GTN). Vascular response to GTN was assessed via applanation tonometry, as change in augmentation index (AIx) over time. Platelet responsiveness to GTN and sodium nitroprusside (SNP) was determined, as inhibition of ADP-induced platelet aggregation. O (2) (-) release was evaluated during aggregation via lucigenin-derived chemiluminescence. Platelet responsiveness to the NO donors GTN and SNP was impaired, denoting the presence of severe NO resistance. Hydralazine therapy decreased systolic blood pressure by 6.8 +/- 10.5 (S.D.) mmHg (p = 0.02), and caused a reduction in AIx by 15 +/- 24% (p = 0.03). However, there were no significant changes in platelet aggregability and associated O (2) (-) release, or in platelet or vascular responses to NO donor. The results of the present study do not support the assumption that hydralazine could be viewed as a "NO enhancer" there is no evidence of attenuation of NO resistance by hydralazine treatment.
Publisher: Elsevier BV
Date: 02-2016
Publisher: Springer Science and Business Media LLC
Date: 10-06-2021
DOI: 10.1007/S11864-021-00868-7
Abstract: Radiation therapy is a key component of modern-day cancer therapy and can reduce the rates of recurrence and death from cancer. However, it can increase risk of cardiovascular (CV) events, and our understanding of the timeline associated with that risk is shorter than previously thought. Risk mitigation strategies, such as different positioning techniques, and breath hold acquisitions as well as baseline cardiovascular risk stratification that can be undertaken at the time of radiotherapy planning should be implemented, particularly for patients receiving chest radiation therapy. Primary and secondary prevention of cardiovascular disease (CVD), as appropriate, should be used before, during, and after radiation treatment in order to minimize the risks. Opportunistic screening for subclinical coronary disease provides an attractive possibility for primary/secondary CVD prevention and thus mitigation of long-term CV risk. More data on long-term clinical usefulness of this strategy and development of appropriate management pathways would further strengthen the evidence for the implementation of such screening. Clear guidelines in initial cardiovascular screening and cardiac aftercare following radiotherapy need to be formulated in order to integrate these measures into everyday clinical practice and policy and subsequently improve post-treatment morbidity and mortality for these patients.
Publisher: Wiley
Date: 12-01-2011
Publisher: IOP Publishing
Date: 06-12-2010
DOI: 10.1088/0953-8984/23/1/015302
Abstract: Pt-decorated Au nanostructures and bimetallic PtAu nanoparticles have been shown to act as catalysts. Consequently we investigate the formation of extended Pt decorations of an Au island edge on Au(111) as possible catalysts. The investigation is by simulation using the kinetic Monte Carlo method. The effects of varying the rate of deposition of Pt atoms and the simulation temperature on the morphology of the resulting Pt nanostructures were investigated. The thickness and roughness of the nanostructures are readily influenced, with temperature being the more important factor. A combination of both high temperature and low deposition rate was the most effective at reducing the roughness. PtAu alloying in the Au island edge was identified. This work is (to the best of our knowledge) the first kinetic Monte Carlo simulation study of the formation of Pt nanostructures on Au. We demonstrate how the morphology of the Pt nanostructures can be controlled. The nanostructures studied here, comprising an adjustable mix of Pt overlayers and novel 1D PtAu surface alloys, are expected to be of considerable interest as potential bimetallic nano-catalysts.
Publisher: Elsevier BV
Date: 08-2023
Publisher: American Society of Hematology
Date: 27-09-2022
DOI: 10.1182/BLOODADVANCES.2022007938
Abstract: Bruton’s tyrosine kinase inhibitors (BTKis) have altered the treatment landscape for chronic lymphocytic leukemia (CLL) by offering effective and well-tolerated therapeutic options. However, since the approval of ibrutinib, concern has risen regarding the risk of cardiovascular (CV) adverse events, including atrial fibrillation (AF), hypertension, and heart failure. Newer BTKis appear to have lower CV risks, but data are limited. It is important to understand the risks posed by BTKis and how those risks interact with in idual patients, and we convened a panel of physicians with expertise in CLL and CV toxicities in oncology to develop evidence-based consensus recommendations for community hematologists and oncologists. Care providers should thoroughly assess a patient’s CV risk level before treatment initiation, including established CV diseases and risk factors, and perform investigations dependent on preexisting diseases and risk factors, including an electrocardiogram (ECG). For patients with high CV risk, BTKi treatment is often appropriate in consultation with a multidisciplinary team (MDT), and more selective BTKis, including acalabrutinib and zanubrutinib, are preferred. BTKi treatment should generally be avoided in patients with a history of heart failure. Ibrutinib should be avoided in patients with a history of ventricular arrhythmias, but the risk of newer drugs is not yet known. Finally, an MDT is crucial to help manage emerging toxicities with the goal of maintaining BTKi therapy, if possible. Optimizing heart failure, arrhythmia, and hypertension control will likely improve tolerance and maintenance of BTKi therapy. However, additional studies are needed to identify the most optimal strategy for these drugs.
Publisher: MDPI AG
Date: 28-06-2023
DOI: 10.3390/JCDD10070274
Abstract: Secreted frizzled-related protein 5 (SFRP5) is a novel anti-inflammatory adipokine that may play a role in cardiovascular development and disease. However, there is yet to be a comprehensive investigation into whether circulating SFRP5 can be a biomarker for cardiac function. Plasma SFRP5 levels were measured via ELISA in 262 patients admitted to a cardiology unit. Plasma SFRP5 levels were significantly lower in patients with a history of heart failure (HF), coronary artery disease (CAD), and atrial fibrillation (AF p = 0.001). In univariate analyses, SFRP5 levels were also significantly positively correlated with left ventricular ejection fraction (LVEF) (r = 0.52, p 0.001) and negatively correlated with E/E’ (r = −0.30, p 0.001). Patients with HF, CAD, low LVEF, low triglycerides, high CRP, and high eGFR were associated with lower SFRP5 levels independent of age, BMI, or diabetes after multivariate analysis (overall model r = 0.729, SE = 0.638). Our results show that low plasma SFRP5 levels are independently associated with the presence of HF, CAD, and, importantly, impaired LV function. These results suggest a potential role of SFRP5 as a biomarker, as well as a mediator of cardiac dysfunction independent of obesity and metabolic regulation.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.NIOX.2013.08.006
Abstract: Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10μM) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10μM) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200μM) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10μM) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator.
Publisher: MDPI AG
Date: 09-04-2023
DOI: 10.3390/JCM12082790
Abstract: The role of soluble suppression of tumorigenicity (sST2) as a biomarker in predicting clinical outcomes in patients with cardiovascular diseases (CVD) has not been fully elucidated. In this study, we sought to determine the relationship between sST2 levels and any unplanned hospital readmissions due to a major adverse cardiovascular event (MACE) within 1 year of first admission. Patients (n = 250) admitted to the cardiology unit at John Hunter Hospital were recruited. Occurrences of MACE, defined as the composite of total death, myocardial infarction (MI), stroke, readmissions for heart failure (HF), or coronary revascularization, were recorded after 30, 90, 180, and 365 days of first admission. On univariate analysis, patients with atrial fibrillation (AF) and HF had significantly higher sST2 levels vs. those who did not. Increasing levels of sST2 by quartiles were significantly associated with AF, HF, older age, low hemoglobin, low eGFR, and high CRP levels. On multivariate analysis: high sST2 levels and diabetes remained as risk predictors of any MACE occurrence an sST2 level in the highest quartile (Q4: .4 ng/mL) was independently associated with older age, use of beta-blockers, and number of MACE events within a 1 year period. In this patient cohort, elevated sST2 levels are associated with unplanned hospital admission due to MACE within 1 year, independent of the nature of the index cardiovascular admission.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.AMJCARD.2011.06.047
Abstract: Takotsubo cardiomyopathy (TTC) is characterized by reversible left ventricular (LV) systolic dysfunction independent of fixed coronary disease or coronary spastic pathogenesis. A number of investigators have documented marked elevation of natriuretic peptide levels at presentation in such patients. We sought to determine the pattern, extent, and determinants of the release of N-terminal pro-B type natriuretic peptide/B type natriuretic peptide (NT-proBNP/BNP) in patients with TTC. We evaluated NT-proBNP/BNP release acutely and during the first 3 months in 56 patients with TTC (96% women, mean age 69 ± 11 years). The peak plasma NT-proBNP levels were compared to the pulmonary capillary wedge pressure and measures of regional and global LV systolic dysfunction (systolic wall stress, wall motion score index, and LV ejection fraction) as potential determinants of NT-proBNP/BNP release. In patients with TTC, the plasma concentrations of NT-proBNP (median 4,382 pg/ml, interquartile range 2,440 to 9,019) and BNP (median 617 pg/ml, interquartile range 426 to 1,026) were substantially elevated and increased significantly during the first 24 hours after the onset of symptoms (p = 0.001), with slow and incomplete resolution during the 3 months thereafter. The peak NT-proBNP levels exhibited no significant correlation with either pulmonary capillary wedge pressure or systolic wall stress. However, the peak NT-proBNP level correlated significantly with the simultaneous plasma normetanephrine concentrations (r = 0.53, p = 0.001) and the extent of impairment of LV systolic function, as measured by the wall motion score index (r = 0.37, p = 0.008) and LV ejection fraction (r = -0.39, p = 0.008). In conclusion, TTC is associated with marked and persistent elevation of NT-proBNP/BNP levels, which correlated with both the extent of catecholamine increase and the severity of LV systolic dysfunction.
Publisher: Public Library of Science (PLoS)
Date: 10-05-2017
Publisher: Aging and Disease
Date: 2019
Publisher: Wiley
Date: 19-12-2017
DOI: 10.1002/EHF2.12239
Publisher: Elsevier BV
Date: 10-2019
Publisher: Oxford University Press (OUP)
Date: 05-2015
DOI: 10.1093/EHJCI/JEV051
Location: United States of America
Start Date: 2018
End Date: 2021
Funder: National Heart Foundation of Australia
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