ORCID Profile
0000-0003-0990-2548
Current Organisations
Royal Adelaide Hospital
,
Mildura Cardiology
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2019
Publisher: Wiley
Date: 14-07-2014
DOI: 10.1111/CTR.12402
Abstract: Despite improvements in survival following renal transplantation, high rates of cardiovascular morbidity and mortality remain. Persistence of arterio-venous fistulae (AVF) may contribute to maladaptive cardiovascular remodeling and poor health outcomes in this cohort. Utilizing recent advances in cardiovascular magnetic resonance imaging (CMR), we prospectively evaluated alterations in cardiac and vascular structure and function six months after elective ligation of AVF, following stable, successful renal transplantation. Eighteen subjects underwent CMR evaluation of cardiac structure and function, aortic distensibility and endothelial function prior to AVF ligation and at six months. At follow-up, while left ventricular ejection fraction was unchanged, mean cardiac output decreased by 15.6% (9.6 ± 2.9 L/min vs. 8.1 ± 2.3 L/min, p = 0.004) and left ventricular mass had regressed by 10% (166 ± 56 g vs. 149 ± 51 g, p = 0.0001). Significant improvements were also noted in right ventricular and biatrial structure and function. Aortic distensibility was unchanged at follow-up, but endothelial dependent vasodilatation had improved (2.5 ± 6.5% vs. 8.0 ± 5.9%, p = 0.04). Elective AVF ligation following successful renal transplantation is associated with improvements in left ventricular mass, right ventricular, and biatrial structure and function. Further randomized studies are warranted to determine the potential clinical improvement following AVF ligation in this cohort.
Publisher: Wiley
Date: 02-2017
DOI: 10.1111/IMJ.13325
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-03-2022
Abstract: The practice pattern and outcome of medical devices following their regulatory approval may differ by country. The aim of this study is to compare postapproval national clinical registry data on transcatheter aortic valve replacement between the United States and Japan on patient characteristics, periprocedural outcomes, and the variability of outcomes as a part of a partnership program (Harmonization‐by‐Doing) between the 2 countries. The patient‐level data were extracted from the US Society of Thoracic Surgeons /American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) and the J‐TVT (Japanese Transcatheter Valvular Therapy) registry, respectively, to analyze transcatheter aortic valve replacement outcomes between 2013 and 2019. Data entry for these registries was mandated by the federal regulators, and the majority of variable definitions were harmonized to allow direct data comparison. A total of 244 722 transcatheter aortic valve replacements from 646 institutions in the United States and 26 673 transcatheter aortic valve replacements from 171 institutions in Japan were analyzed. Median volume per site was 65 (interquartile range, 45–97) in the United States and 28 (interquartile range, 19–41) in Japan. Overall, patients in J‐TVT were older (United States: mean‐age, 80.1±8.7 versus Japan: 84.4±5.2 P .001), were more frequently women (45.9% versus 68.1% P .001), and had higher median Society of Thoracic Surgeons Predicted Risk of Mortality (5.27% versus 6.20% P .001) than patients in the United States. Japan had lower unadjusted 30‐day mortality (1.3% versus 3.2% P .001) and composite outcomes of death, stroke, and bleeding (17.5 versus 22.5% P .001) but had higher conversion to open surgery (0.94% versus 0.56% P .001). This collaborative analysis between the United States and Japan demonstrated the feasibility of international comparison using the national registries coded under mutual variable definitions. Both countries obtained excellent outcomes, although the Japanese had lower 30‐day mortality and major morbidity. Harmonization‐by‐Doing is one of the key steps needed to build global‐level learning to improve patient outcomes.
Publisher: Elsevier BV
Date: 2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-11-2019
DOI: 10.1161/CIRCULATIONAHA.119.042891
Abstract: High-sensitivity troponin assays promise earlier discrimination of myocardial infarction. Yet, the benefits and harms of this improved discriminatory performance when incorporated within rapid testing protocols, with respect to subsequent testing and clinical events, has not been evaluated in an in-practice patient-level randomized study. This multicenter study evaluated the noninferiority of a 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol in comparison with a 0/3-hour masked hs-cTnT protocol in patients with suspected acute coronary syndrome presenting to the emergency department (ED). Patients were randomly assigned to either a 0/1-hour hs-cTnT protocol (reported to the limit of detection [ ng/L]) or masked hs-cTnT reported to ≤29 ng/L evaluated at 0/3-hours (standard arm). The 30-day primary end point was all-cause death and myocardial infarction. Noninferiority was defined as an absolute margin of 0.5% determined by Poisson regression. In total, 3378 participants with an emergency presentation were randomly assigned between August 2015 and April 2019. Ninety participants were deemed ineligible or withdrew consent. The remaining participants received care guided either by the 0/1-hour hs-cTnT protocol (n=1646) or the 0/3-hour standard masked hs-cTnT protocol (n=1642) and were followed for 30 days. Median age was 59 (49–70) years, and 47% were female. Participants in the 0/1-hour arm were more likely to be discharged from the ED (0/1-hour arm: 45.1% versus standard arm: 32.3%, P .001) and median ED length of stay was shorter (0/1-hour arm: 4.6 [interquartile range, 3.4–6.4] hours versus standard arm: 5.6 (interquartile range, 4.0–7.1) hours, P .001). Those randomly assigned to the 0/1-hour protocol were less likely to undergo functional cardiac testing (0/1-hour arm: 7.5% versus standard arm: 11.0%, P .001). The 0/1-hour hs-cTnT protocol was not inferior to standard care (0/1-hour arm: 18/1646 [1.1%] versus 16/1642 [1.0%] incidence rate ratio, 1.06 [ 0.53–2.11], noninferiority P value=0.001, superiority P value=0.744), although an increase in myocardial injury was observed. Among patients discharged from ED, the 0/1-hour protocol had a negative predictive value of 99.6% (95% CI, 99.0–99.9%) for 30-day death or myocardial infarction. This in-practice evaluation of a 0/1-hour hs-cTnT protocol embedded in ED care enabled more rapid discharge of patients with suspected acute coronary syndrome. Improving short-term outcomes among patients with newly recognized troponin T elevation will require an evolution in management strategies for these patients. URL: www.anzctr.org.au . Unique identifier: ACTRN12615001379505.
Publisher: Elsevier BV
Date: 10-2016
Publisher: BMJ
Date: 10-05-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-01-2021
Abstract: Evidence‐based therapies are generally underused for cardiovascular risk reduction however, less is known about contemporary patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Pharmacy and medical claims data from within Anthem were queried for patients with established atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Using an index date of April 18, 2018, we evaluated the proportion of patients with a prescription claim for any of the 3 evidence‐based therapies on, or covering, the index date ±30 days: high‐intensity statin, angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker, and sodium glucose cotransporter‐2 inhibitor or glucagon‐like peptide‐1 receptor agonist. The potential benefit of achieving 100% adoption of all 3 evidence‐based therapies was simulated using pooled treatment estimates from clinical trials. Of the 155 958 patients in the s le, 24.7% were using a high‐intensity statin, 53.1% were using an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker, and 9.9% were using either an sodium glucose cotransporter‐2 inhibitor or glucagon‐like peptide‐1 receptor agonists. Overall, only 2.7% of the population were covered by prescriptions for all 3 evidence‐based therapies, and 37.4% were on none of them. Over a 12‐month period, 70.6% of patients saw a cardiologist, while only 18% saw an endocrinologist. Increasing the use of evidence‐based therapies to 100% over 3 years of treatment could be expected to reduce 4546 major atherosclerotic cardiovascular events (myocardial infarction, stroke, or cardiovascular death) in eligible but untreated patients. Alarming gaps exist in the contemporary use of evidence‐based therapies in this large population of insured patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. These data provide a call to action for patients, providers, industry, regulators, professional societies, and payers to close these gaps in care.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 05-2011
Publisher: Elsevier BV
Date: 05-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2016
Publisher: Elsevier BV
Date: 06-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-07-2021
DOI: 10.1161/CIRCULATIONAHA.121.053766
Abstract: Multiple sodium glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to impart significant cardiovascular and kidney benefits, but are underused in clinical practice. Both SGLT-2i and GLP-1RA were first studied as glucose-lowering drugs, which may have impeded uptake by cardiologists in the wake of proven cardiovascular efficacy. Their significant effect on cardiovascular and kidney outcomes, which are largely independent of glucose-lowering effects, must drive a broader use of these drugs. Cardiologists are 3 times more likely than endocrinologists to see patients with both type 2 diabetes and cardiovascular disease, thus they are ideally positioned to share responsibility for SGLT-2i and GLP-1RA treatment with primary care providers. In order to increase adoption, SGLT-2i and GLP-1RA must be reframed as primarily cardiovascular and kidney disease risk-reducing agents with a side effect of glucose-lowering. Coordinated and multifaceted interventions engaging clinicians, patients, payers, professional societies, and health systems must be implemented to incentivize the adoption of these medications as part of routine cardiovascular and kidney care. Greater use of SGLT-2i and GLP-1RA will improve outcomes for patients with type 2 diabetes at high risk for cardiovascular and kidney disease.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 02-2023
DOI: 10.1016/J.AHJ.2022.10.079
Abstract: Several medications that are proven to reduce cardiovascular events exist for in iduals with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease, however they are substantially underused in clinical practice. Clinician, patient, and system-level barriers all contribute to these gaps in care yet, there is a paucity of high quality, rigorous studies evaluating the role of interventions to increase utilization. The COORDINATE-Diabetes trial randomized 42 cardiology clinics across the United States to either a multifaceted, site-specific intervention focused on evidence-based care for patients with T2DM or standard of care. The multifaceted intervention comprised the development of an interdisciplinary care pathway for each clinic, audit-and-feedback tools and educational outreach, in addition to patient-facing tools. The primary outcome is the proportion of in iduals with T2DM prescribed three key classes of evidence-based medications (high-intensity statin, angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and either a sodium/glucose cotransporter-2 inhibitor (SGLT-2i) inhibitor or glucagon-like peptide 1 receptor agonist (GLP-1RA) and will be assessed at least 6 months after participant enrollment. COORDINATE-Diabetes aims to identify strategies that improve the implementation and adoption of evidence-based therapies.
Publisher: Elsevier BV
Date: 2013
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: Ovid Technologies (Wolters Kluwer Health)
Date: 2022
DOI: 10.1161/CIRCINTERVENTIONS.121.010909
Abstract: Percutaneous coronary intervention is performed by operators with differing experience, technique, and case mix. It is unknown if operator practice patterns impact patient outcomes. We sought to determine if a cluster algorithm can identify distinct profiles of percutaneous coronary intervention operators and if these profiles are associated with patient outcomes. Operators performing at least 25 annual procedures between 2014 and 2018 were clustered using an agglomerative hierarchical clustering algorithm. Risk-adjusted in-hospital mortality was compared between clusters. We identified 4 practice profiles among 7706 operators performing 2 937 419 procedures. Cluster 1 (n=3345) demonstrated case mix and practice patterns similar to the national median. Cluster 2 (n=1993) treated patients with lower clinical acuity and were less likely to use intracoronary diagnostics, atherectomy, and radial access. Cluster 3 (n=1513) had the lowest case volume, were more likely to work at rural hospitals, and cared for a higher proportion of patients with ST-segment–elevation myocardial infarction and cardiogenic shock. Cluster 4 (n=855) had the highest case volume, were most likely to treat patients with high anatomic complexity and use atherectomy, intracoronary diagnostics, and mechanical support. Compared with cluster 1, adjusted in-hospital mortality was similar for cluster 2 (estimated difference, −0.03 [95% CI, −0.10 to 0.04]), higher for cluster 3 (0.14 [0.07–0.22]), and lower for cluster 4 (−0.15 [−0.24 to −0.06]). Distinct percutaneous coronary intervention operator profiles are differentially associated with patient outcomes. A phenotypic approach to physician assessment may provide actionable feedback for quality improvement.
Publisher: Oxford University Press (OUP)
Date: 16-03-2016
Publisher: Springer Science and Business Media LLC
Date: 09-10-2014
DOI: 10.1007/S10554-014-0545-2
Abstract: Little is known of the relationship between coronary atheroma composition and corresponding endothelial dysfunction. We tested the hypothesis that segmental epicardial vasoreactivity relates to atheroma composition in patients with non-ST segment elevation myocardial infarction (NSTEMI) in vivo. In 23 NSTEMI patients referred for coronary angiography, a non-culprit vessel underwent intracoronary salbutamol (0.30 μg/min) provocation during automated IVUS pullback. A 40 MHz rotational IVUS catheter delivered radiofrequency signals at constant 67 μm intervals via a custom-built IVUS console (iMAP, iLAB, Boston Scientific). Macrovascular response [change in segmental lumen volume (SLV) at baseline and following salbutamol], percent atheroma volume (PAV) and tissue composition was evaluated in 187 contiguous non-overlapping 5 mm coronary segments. Compared with segments that dilated, constrictive segments showed similar SLV, but greater vessel volumes and PAV at baseline. The extent of necrotic and lipidic plaque was significantly greater in constrictive segments, whereas fibrotic plaque content was significantly greater in segments that dilated. Calcific plaque content did not relate to endothelium-dependent vasoreactivity. The change in SLV correlated inversely with the amount of lipidic and necrotic plaque (both r = -0.23, p = 0.002), and directly with fibrotic plaque content (r = 0.23, p = 0.002). In a multivariable model, the extent of both lipidic and necrotic plaque independently associated with segmental vasoconstriction (β = 1.2, p = 0.023 β = 0.66, p = 0.027). Following NSTEMI, both lipidic and necrotic plaque content each associate with segmental endothelial dysfunction. The link between plaque composition and vessel reactivity provides a mechanistic basis of the pathogenesis associated with vulnerable plaque in humans in vivo.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 03-2023
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: Oxford University Press (OUP)
Date: 14-07-2014
DOI: 10.1093/EHJCI/JEU133
Abstract: While the relationship between epicardial coronary vasomotor reactivity and cardiovascular events is well established, this observation has yet to be evaluated within the left main coronary artery (LMCA) in humans in vivo. Our aims were to test the endothelium-dependent vasomotor properties of the LMCA, and to compare these responses to downstream epicardial segments. Thirty patients referred for coronary angiography underwent intracoronary (IC) salbutamol provocation during intravascular ultrasound imaging within a non-critically diseased, left-sided conduit vessel. Macrovascular vasomotor response [change in average lumen area (LA) at baseline and following 5 min of 0.30 µg/min IC salbutamol] and percent atheroma volume (PAV) were evaluated in 30 LMCA, 42 proximal, 109 mid, and 132 distal epicardial coronary segments. In comparison with all other segments, the LMCA had the greatest lumen and vessel areas (P < 0.001), yet the proximal epicardial segments contained the greatest PAV (P < 0.02). The mid and distal epicardial segments displayed significant endothelium-dependent vasodilatation from baseline (P = 0.017 and <0.001, respectively) however, the proximal epicardial and LMCA segments did not (P = 0.45 and 0.16, respectively). Significant segmental vasomotor heterogeneity was noted in all 30 patients, with opposing vasomotor responses between adjacent LMCA and epicardial segments. Across all segments, baseline LA inversely correlated with the % change in LA (r = -0.16, P = 0.0005). Endothelium-dependent vasomotor reactivity is heterogenous within the conduit coronary system. Vascular dynamic responses were less prominent in the larger calibre LMCA and proximal epicardial segments. This may, in part, relate to higher shear stress in smaller, distal segments and yet also may explain the propensity for culprit plaques to cluster proximally.
Publisher: Elsevier BV
Date: 2012
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: 2013
DOI: 10.1016/J.HRTHM.2012.08.043
Abstract: Obesity is associated with atrial fibrillation (AF) however, the mechanisms by which it induces AF are unknown. To examine the effect of progressive weight gain on the substrate for AF. Thirty sheep were studied at baseline, 4 months, and 8 months, following a high-calorie diet. Ten sheep were s led at each time point for cardiac magnetic resonance imaging and hemodynamic studies. High-density multisite biatrial epicardial mapping was used to quantify effective refractory period, conduction velocity, and conduction heterogeneity index at 4 pacing cycle lengths and AF inducibility. Histology was performed for atrial fibrosis, inflammation, and intramyocardial lipidosis, and molecular analysis was performed for endothelin-A and -B receptors, endothelin-1 peptide, platelet-derived growth factor, transforming growth factor β1, and connective tissue growth factor. Increasing weight was associated with increasing left atrial volume (P = .01), fibrosis (P = .02), inflammatory infiltrates (P = .01), and lipidosis (P = .02). While there was no change in the effective refractory period (P = .2), there was a decrease in conduction velocity (P<.001), increase in conduction heterogeneity index (P<.001), and increase in inducible (P = .001) and spontaneous (P = .001) AF. There was an increase in atrial cardiomyocyte endothelin-A and -B receptors (P = .001) and endothelin-1 (P = .03) with an increase in adiposity. In association, there was a significant increase in atrial interstitial and cytoplasmic transforming growth factor β1 (P = .02) and platelet-derived growth factor (P = .02) levels. Obesity is associated with atrial electrostructural remodeling. With progressive obesity, there were changes in atrial size, conduction, histology, and expression of profibrotic mediators. These changes were associated with spontaneous and more persistent AF.
Publisher: Oxford University Press (OUP)
Date: 17-12-2018
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: MDPI AG
Date: 20-08-2022
DOI: 10.3390/IJMS23169417
Abstract: Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2020
DOI: 10.1007/S40256-019-00363-3
Abstract: Despite the widespread use of statins in the setting of high cardiovascular risk, many patients continue to experience clinical events. This highlights the need to identify additional therapeutic strategies for high-risk patients. Interest in the use of omega-3 polyunsaturated fatty acids to prevent cardiovascular disease has been high for several decades. Despite promising results from before the statin era, many clinical trials have produced disappointing findings regarding products containing conventional doses of omega-3 fatty acids. More recent clinical trials using high doses of omega-3 fatty acids in targeted populations have suggested potential benefit when targeting the risk driven by atherogenic dyslipidemia. We review the clinical implications of completed and ongoing trials.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Informa UK Limited
Date: 09-2014
DOI: 10.2147/IJNRD.S66390
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.ECL.2017.10.004
Abstract: Cardiovascular disease is the most frequent cause of morbidity and mortality among in iduals with diabetes and although there has been significant reduction in excess risk, these in iduals remain at least twice as likely to sustain atherosclerotic events. Aggressive management of traditional factors, such as dyslipidemia, remains the cornerstone of risk mitigation. Diabetes and its associated insulin resistance generate qualitative and quantitative changes in lipid profile, which complicate effective treatment. This review summaries the background to diabetic dyslipidemia and provides a précis of the available management options.
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.JACC.2010.11.045
Abstract: The aim of this study was to characterize the relationship between pericardial fat and atrial fibrillation (AF). Obesity is an important risk factor for AF. Pericardial fat has been hypothesized to exert local pathogenic effects on nearby cardiac structures above and beyond that of systemic adiposity. One hundred ten patients undergoing first-time AF ablation and 20 reference patients without AF underwent cardiac magnetic resonance imaging for the quantification of periatrial, periventricular, and total pericardial fat volumes using a previously validated technique. Together with body mass index and body surface area, these were examined in relation to the presence of AF, the severity of AF, left atrial volume, and long-term AF recurrence after ablation. Pericardial fat volumes were significantly associated with the presence of AF, AF chronicity, and AF symptom burden (all p values <0.05). Pericardial fat depots were also predictive of long-term AF recurrence after ablation (p = 0.035). Finally, pericardial fat depots were also associated with left atrial volume (total pericardial fat: r = 0.46, p < 0.001). Importantly, these associations persisted after multivariate adjustment and additional adjustment for body weight. In contrast, however, systemic measures of adiposity, such as body mass index and body surface area, were not associated with these outcomes in multivariate-adjusted models. Pericardial fat is associated with the presence of AF, the severity of AF, left atrial volumes, and poorer outcomes after AF ablation. These associations are both independent of and stronger than more systemic measures of adiposity. These findings are consistent with the hypothesis of a local pathogenic effect of pericardial fat on the arrhythmogenic substrate supporting AF.
Publisher: SAGE Publications
Date: 29-11-2016
Abstract: Barriers to climate change adaptation might not lie so much in ‘gaps’ in scientific or technical understandings but rather in the complexities of social, institutional and cultural transitions in climate change governance. Effective responses to complex environmental issues seem to require ‘co-learning for systemic governance transformations’. However, this process remains poorly understood. This article analyses the performance and orchestration of governance learning for systemic transformation in practice, drawing on ex les from the international climate change adaptation and water governance (CADWAGO) project. We show that in these ex les the interplay of ‘separating’ and ‘connecting’ is central to transforming governance in the European water management landscape. The article concludes that an orientation to boundary work and co-production of knowledge contributes to scientific narratives that can inspire meaningful connective action and move complex socioecological systems into a more sustainable trajectory.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.HRTHM.2009.06.007
Abstract: Abstract presentation at conferences provides the opportunity to rapidly communicate research findings. The outcome and impact of publications arising from cardiac electrophysiology abstracts are not known. The purpose of this study was to examine the characteristics of abstracts presented at the annual scientific sessions of Heart Rhythm Society (HRS), their publication rate, and the indexed impact of subsequent publications. Two independent database searches (MEDLINE and EMBASE) were performed by cross-referencing authors and keywords from abstracts originally presented at HRS in 2003. ISI Web of Knowledge was accessed for impact factors and citation rates. A total of 790 abstracts were presented, of which 377 (47.7%) resulted in publication of an original article. Median time to publication was 1.39 years (interquartile range [IQR] 0.88-2.30 years), and the median impact factor and citation rate of published articles was 4.14 (IQR 3.48-11.05) and 10 (IQR 4-25), respectively. Experimental research abstract category (odds ratio [OR] 2.03, P <.001), randomized study design (OR 0.53, P = .02), and positive findings (OR 0.80, P = .06) were independently predictive of publication by stepwise logistic regression. Independent predictors of higher citation rates were randomized study design (P = .03) and impact factor of the publishing journal (P <.001). Almost half of all abstracts presented at HRS resulted in publication in journals with a high impact factor. Experimental research abstracts, those with a randomized study design, and those demonstrating positive findings were predictors of subsequent publication. Randomized study design and greater impact factor of the publishing journal were found to predict higher citation rates.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.CCL.2017.12.005
Abstract: Type 2 diabetes is associated with elevated levels of triglycerides and small, dense low-density lipoprotein particles, in addition to low levels of high-density lipoprotein cholesterol. Clinical trials have demonstrated the clear cardiovascular benefit of use of statin therapy in patients with diabetes. Additional lipid-modifying agents are typically guided by the presence of additional lipid abnormalities. The optimal use of existing lipid agents and the potential for novel therapies in patients with diabetes is reviewed.
Publisher: Elsevier BV
Date: 05-2022
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.AHJ.2022.10.002
Abstract: Appropriate use criteria (AUC) have been developed to promote the rational use of percutaneous coronary intervention (PCI) among clinicians and to provide benchmarking feedback to hospitals. The original AUC were published in 2012 and subsequently updated in 2017 to reflect emerging, contemporary evidence however the degree to which the updated guidance re-classifies PCI appropriateness is unknown. Elective PCI cases from March 1, 2018 until June 30, 2021 were identified from within the NCDR CathPCI database. PCI cases were classified as 'appropriate,' 'uncertain' or 'inappropriate' under 2012 AUC and 'appropriate,' 'may be appropriate' or 'rarely appropriate' under 2017 AUC those with missing data elements were termed 'not mappable.' Groups that 'remained appropriate' (appropriate in both 2012 and 2017), 'became non-appropriate' ('appropriate' in 2012 but became either 'may be appropriate' or 'rarely appropriate in 2017) and 'became appropriate' ('appropriate' in 2017 but were 'uncertain' or 'inappropriate' in 2012) were descriptively compared. Concordance was assessed by calculation of Cohen's Kappa. A total of 245,196 patients underwent elective PCI across 1669 centers. By 2012 AUC, 44% were classified 'appropriate,' 28% were 'uncertain' and 16% were 'inappropriate' compared with 2017 AUC which considered 34% 'appropriate', 56% may be 'appropriate' and 4% 'rarely appropriate'. Overall fair agreement was observed with a Kappa statistic of 0.40 (95%CI 0.396-0.403). Compared with PCI that 'remained appropriate' under the 2017 AUC, PCI that 'became non-appropriate' in 2017 were more likely to be asymptomatic, less likely to be on anti-anginals and less likely to have complex lesions. Compared with PCI that 'became non-appropriate', PCI that 'became appropriate' had a higher proportion of atypical and non-anginal symptoms and were less likely to have had positive functional tests. Procedural related outcomes were similar across all groups. A total of 29 429 PCI (12.0%) were not mappable by 2012 AUC while 16 077 (6.6%) were not mappable by 2017 AUC. In this contemporary analysis of patients undergoing PCI in the United States, only fair agreement between the 2012 and updated 2017 AUC was observed. While some of this reflects the intention of the updated guidance, the large proportion that were considered 'maybe appropriate' or who 'became non-appropriate' reflect the difficulties of documenting and implementing contemporary AUC guidance.
Publisher: Springer Science and Business Media LLC
Date: 25-03-2012
DOI: 10.1007/S00330-012-2420-7
Abstract: Advances in the management of myocardial infarction have resulted in substantial reductions in morbidity and mortality. However, after acute treatment a number of diagnostic and prognostic questions often remain to be answered, whereby cardiac imaging plays an essential role. For ex le, some patients will sustain early mechanical complications after infarction, while others may develop significant ventricular dysfunction. Furthermore, many in iduals harbour a significant burden of residual coronary disease for which clarification of functional ischaemic status and/or viability of the suspected myocardial territory is required. Cardiac magnetic resonance (CMR) imaging is well positioned to fulfil these requirements given its unparalleled capability in evaluating cardiac function, stress ischaemia testing and myocardial tissue characterisation. This review will focus on the utility of CMR in resolving diagnostic uncertainty, evaluating early complications following myocardial infarction, assessing inducible ischaemia, myocardial viability, ventricular remodelling and the emerging role of CMR-derived measures as endpoints in clinical trials. Cardiac magnetic resonance (CMR) imaging identifies early complications after myocardial infarction. • Adenosine stress CMR can reliably assess co-existing disease in non-culprit arteries. • Assessment of infarct size and microvascular obstruction a robust prognostic indicator. • Assessment of myocardial viability is important to guide revascularisation decision-making.
Publisher: Informa UK Limited
Date: 12-2011
DOI: 10.2147/PROM.S9834
Publisher: Oxford University Press (OUP)
Date: 08-03-2018
Publisher: Oxford University Press (OUP)
Date: 15-09-2015
DOI: 10.1093/EHJCI/JEV232
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.AHJ.2017.05.004
Abstract: Protocols incorporating high-sensitivity troponin to guide decision making in the disposition of patients with suspected acute coronary syndromes (ACS) in the emergency department have received a lot of attention. Traditionally, patients with chest pain have required long periods of observation in emergency department before being deemed safe for discharge. In an era of limited health service resources, a protocol that could discharge patients safely within an hour of presentation is extremely attractive. Unfortunately, despite incorporation into some guidelines, these protocols have not been subjected to randomized comparisons evaluating safety, effectiveness, and cost-effectiveness. This study is designed to provide the evidence required to allow key decision makers to implement these protocols: specifically, to provide evidence that a decision rule based on 0- and 1-hour high-sensitivity troponin T (hs-TnT) is safe, provides noninferior outcomes in all patients with suspected ACS, and that implementation of a rapid troponin protocol leads to efficient care. This prospective pragmatic trial (n=5,400, 5 hospitals) randomly allocates patients with suspected ACS to either a 0/1-hour hs-TnT protocol as advocated in clinical guidelines, versus usual care of standard troponin reporting evaluated at 3 and 6hours. The primary effectiveness composite end points of this study are all-cause death and new/recurrent ACS within 30days. To evaluate cost-effectiveness, follow-up will determine clinical events, quality of life, and resource utilization within 12 months. Demonstrating that a 0/1-hour hs-TnT protocol improves the effectiveness and efficiency of care within a robust comparative study will fill an evidence gap that currently limits the translation of more precise hs-TnT testing into better patient and health service outcomes.
Publisher: Oxford University Press (OUP)
Date: 27-09-2011
Abstract: The interaction between coronary β(2)-adrenoreceptors and segmental plaque burden is complex and poorly understood in humans. We aimed to validate intracoronary (IC) salbutamol as a novel endothelium-dependent vasodilator utilizing intravascular ultrasound (IVUS), and thus assess relationships between coronary β(2)-adrenoreceptors, regional plaque burden and segmental endothelial function. In 29 patients with near-normal coronary angiograms, IVUS-upon-Doppler Flowire imaging protocols were performed. Protocol 1: incremental IC salbutamol (0.15, 0.30, 0.60 μg/min) infusions (15 patients, 103 segments) protocol 2: salbutamol (0.30 μg/min) infusion before and after IC administration of N(G)-monomethyl-L-arginine (L-NMMA) (10 patients, 82 segments). Vehicle infusions (IC dextrose) were performed in 4 patients (21 segments). Macrovascular response [% change segmental lumen volume (ΔSLV)] and plaque burden [per cent atheroma volume (PAV)] were studied in 5-mm coronary segments. Microvascular response [per cent change in coronary blood flow (ΔCBF)] was calculated following each infusion. Intracoronary salbutamol demonstrated significant dose-response ΔSLV and ΔCBF from baseline, respectively (0.15 μg/min: 3.5 ± 1.3%, 28 ± 14%, P = 0.04, P = NS 0.30 μg/min: 5.5 ± 1.4%, 54 ± 17%, P = 0.001, P < 0.0001 0.60 μg/min: 4.8 ± 1.6%, 66 ± 15%, P = 0.02, P < 0.0001), with ΔSLV responses further exemplified in low vs. high plaque burden groups. Salbutamol vasomotor responses were suppressed by l-NMMA, supporting nitric oxide-dependent mechanisms. Vehicle infusions resulted in no significant ΔSLV or ΔCBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a ΔSLV to IC salbutamol (coefficient -0.18, 95% CI -0.32 to -0.044, P = 0.015). Conclusions Intracoronary salbutamol is a novel endothelium-dependent epicardial and microvascular coronary vasodilator. Intravascular ultrasound-derived regional plaque burden is a major determinant of segmental coronary endothelial function.
Publisher: Physicians Postgraduate Press, Inc
Date: 05-12-2013
DOI: 10.4088/PCC.13L01557
Publisher: Elsevier BV
Date: 10-2023
Publisher: Informa UK Limited
Date: 13-09-2012
DOI: 10.3109/09537104.2011.604804
Abstract: Thrombocytopenia, both at baseline and acquired throughout admission is associated with poor clinical outcomes in patients with coronary artery disease. It is not known whether severe thrombocytopenia in patients receiving glycoprotein IIb/IIIa inhibitors (GPI) carries the same risk as thrombocytopenia from other aetiologies. We identified 50 consecutive patients referred for percutaneous coronary intervention (PCI) who developed severe thrombocytopenia (<50 × 10(9) cells/l) and followed their clinical course to 30 days. Two groups were compared: (1) severe thrombocytopenia following GPI usage and (2) severe thrombocytopenia without exposure to GPI. Baseline platelet counts were higher in GPI group (201 ± 62 vs. 112 ± 83 × 10(9) cells/l, p < 0.05). Patients in GPI group had more profound thrombocytopenia yet quicker recovery of platelet counts. The GPI group received fewer blood product transfusions (red cells: 0.1 ± 0.4 vs. 1.3 ± 2.0, p < 0.05, platelets: 0.22 ± 0.6 vs. 1.1 ± 1.7, p < 0.05) and had lower event rates for the primary end point of 30-day mortality (3.7% vs. 42.1%, p < 0.05), and for major bleeding (0% vs. 15.8%, p < 0.05). In conclusion, GPI associated severe thrombocytopenia follows a distinct clinical course when compared to severe thrombocytopenia due to other aetiologies. Our results suggest that patients who develop severe thrombocytopenia following GPI therapy may be managed conservatively with careful monitoring.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Europa Digital & Publishing
Date: 04-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2021
DOI: 10.1161/CIRCOUTCOMES.120.007187
Abstract: Health status assessment is essential for documenting the benefit of transcatheter aortic valve replacement (TAVR) or transcatheter mitral valve repair on patients’ symptoms, function, and quality of life. Health status can also be a powerful marker for subsequent clinical outcomes, but its prognostic importance around the time of both TAVR and transcatheter mitral valve repair has not been fully defined. Among 73 699 patients who underwent transfemoral TAVR or transcatheter mitral valve repair between 2011 and 2018 (mean age, 81.9±7.0 years, 53% men, 92% TAVR), we constructed sequential models examining the association of health status (as assessed with the Kansas City Cardiomyopathy Questionnaire–Overall Summary Score KCCQ-OS) at baseline, 30 days, change from baseline to 30 days, and combinations of these assessments with death and heart failure (HF) hospitalization from 30 days to 1 year. Although higher baseline KCCQ-OS and 30-day KCCQ-OS scores were each associated with lower risk of death and HF hospitalization (in in idual models and in a model including both measures), the 30-day KCCQ-OS was most predictive (death: hazard ratio, 0.89 per 5-point increase [95% CI, 0.89–0.90] HF hospitalization: hazard ratio, 0.91 [95% CI, 0.90–0.91]). The 30-day KCCQ-OS also was most predictive when included in a separate model with change in KCCQ from baseline to 30 days. Similar findings were noted for the outcomes of death and of HF hospitalization, unadjusted and adjusted for patient factors. All interaction terms between procedure type and KCCQ were not significant, suggesting that health status provided similar prognostic information in both procedures. The patient’s assessment of their health status immediately before and 30 days after TAVR and transcatheter mitral valve repair is associated with subsequent risk of death and HF hospitalization, with the 30-day assessment being most strongly associated with outcomes. Our findings support the routine use of KCCQ data as a prognostic tool.
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: Informa UK Limited
Date: 11-12-2013
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.AHJ.2015.02.008
Abstract: Obesity and pericardial adipose tissue are independent risk factors for atrial fibrillation (AF) and adverse cardiac structural remodeling. The effect of weight reduction on pericardial adipose tissue and cardiac structure remains unknown. We prospectively performed cardiac magnetic resonance imaging on 87 participants with AF undergoing either structured weight management (intervention) or general lifestyle advice (control). We measured pericardial adipose tissue, atrial and ventricular volumes, and myocardial mass at baseline and 12 months. In total, 69 participants underwent baseline and 12-month follow-up cardiac magnetic resonance imaging (intervention n = 36 and controls n = 33). From baseline to 12 months, weight loss (kg, mean [95% CI]) was greater in the intervention group from 101.5 kg (97.2-105.8 kg) to 86.5 kg (81.2-91.9 kg) as compared with controls from 102.6 kg (97.2-108.1 kg) to 98.7 kg (91.0-106.3 kg) (time-group interaction P < .001). The intervention group showed a reduction in left atrial volumes (mL) from 105.0 mL (98.9-111.1 mL) to 96.4 mL (91.6-101.1 mL), whereas the change in the control group was from 108.8 mL (99.6-117.9 mL) to 108.9 mL (99.8-118.0 mL) (time-group interaction P < .001). There was a decline in pericardial adipose tissue (cm(3)) from 140.9 cm(3) (129.3-152.4 cm(3)) to 118.8 cm(3) (108.1-129.6 cm(3)) and myocardial mass (g) from 137.6 g (128.1-147.2 g) to 123.1 g (114.5-131.7 g) in the intervention group, whereas the change in the control group was from 143.2 cm(3) (124.6-161.7 cm(3)) to 147.2 cm(3) (128.9-165.4 cm(3)) for pericardial adipose tissue and 138.3 g (124.8-151.8 g) to 140.7 g (127.4-154.1 g) for myocardial mass (both variables, time-group interaction P < .001). Weight reduction results in favorable structural remodeling and a reduction in pericardial adipose tissue burden.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-10-2021
DOI: 10.1161/CIRCULATIONAHA.121.056810
Abstract: The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial. In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months. Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59–2.79] P =0.53). PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. URL: www.clinicaltrials.gov Unique identifier: NCT02663908.
Publisher: BMJ
Date: 15-02-2016
Publisher: Wiley
Date: 07-2011
DOI: 10.1111/J.1540-8175.2011.01394.X
Abstract: Accurate calculation of left ventricular ejection fraction (LVEF) is important for diagnostic, prognostic and therapeutic reasons. Cardiac magnetic resonance (CMR) is the reference standard for LVEF calculation, followed by real time three-dimensional echocardiography (RT3DE). Limited availability of CMR and RT3DE leaves Simpson's rule as the two-dimensional echocardiography (2DE) standard by which LVEF is calculated. We investigated the accuracy of the 16-Segment Regional Wall Motion Score Index (RWMSI) as an alternative method for calculating LVEF by 2DE and compared this to Simpson's rule and CMR. The 2D echocardiograms of 110 patients were studied (LVEF range: 7-74%) 57 of these underwent CMR. A RWMS was applied, based on the consensus opinion of two experienced cardiologists, to each of 16 American Heart Association myocardial segments (RWMSI: hyperkinesis = 3 normal regional contraction = 2 mild hypokinesis = 1.25 severe hypokinesis = 0.75 akinesis = 0 dyskinesis =-1). LVEF was calculated by: LVEF(%) =Σ(16segRWMS)/16×30. LVEF was calculated by Simpson's rule and CMR using standard methods. Results were correlated against CMR. Intertechnique agreement was examined. A P value of<0.05 was considered significant. RWMSI-LVEF correlated strongly with Biplane Simpson's rule (P< 0.001, r = 0.915). RWMSI-LVEF had a strong correlation to CMR (P < 0.001, r = 0.916) Simpson's rule-LVEF had a moderate correlation to CMR (P< 0.001, r = 0.647). In patients with LV dysfunction (EF < 55%), on linear regression analysis, RWMSI-LVEF had a better correlation with CMR than Simpson's rule. Further more Simpson's rule overestimated LVEF compared to CMR (mean difference: -6.12 ± 16.44, P = 0.002) whereas RWMSI did not (mean difference: 2.58 ± 14.80, P = NS). RWMSI-LVEF correlates strongly with CMR with good intertechnique agreement. In centers where CMR and RT3DE are not readily available, the use by experienced in iduals, of the RWMSI for calculating LVEF may be a more simple, accurate, and reliable alternative to Simpson's rule.
Publisher: American Physiological Society
Date: 12-2019
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: 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: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.HLC.2014.01.005
Abstract: Clopidogrel therapy has recently been shown to reduce cardiovascular events in patients with stable vascular disease. This benefit may be due to effects not exclusively related to platelet aggregation. The aim of this study was to evaluate the effect of clopidogrel therapy on microvascular endothelial function in subjects with stable coronary artery disease (CAD). Forty subjects with stable CAD were randomised to clopidogrel therapy (75mg/day) or control. Blood and endothelial function testing occurred at baseline, one week and three months following randomisation. Microvascular endothelial function was assessed via reactive hyperaemic index (RHI). Platelet function was assessed by adenosine diphosphate (ADP)-induced whole blood aggregation and the VerifyNow™ system. Plasma markers of endothelial function (asymmetric dimethylarginine, ADMA) and oxidative stress (myeloperoxidase, MPO) were also tested. The primary endpoint was endothelial function assessment (RHI) at three months. At one week RHI increased by 20±10% in the clopidogrel group this effect was maintained at three months (21±9% increase from baseline P<0.01). A significant decrease in ADP-induced platelet aggregation and P2Y12 reaction units was observed in the clopidogrel therapy group (P<0.01). There was no correlation between endothelial function and platelet function testing in the clopidogrel therapy group. Clopidogrel therapy is associated with improved microvascular endothelial function in patients with stable CAD. This effect is independent of its effects on ADP-induced platelet reactivity.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
DOI: 10.1161/CIRCIMAGING.113.000460
Abstract: Epicardial plaque burden and endothelial function are recognized predictors of coronary events. We aimed to investigate mechanistic relationships between atheroma volume and endothelial function in patients with non–ST-segment–elevation myocardial infarction (NSTEMI) using intravascular ultrasound. In coronary vessels of patients with near-normal or minimal angiographic disease (n=23) and NSTEMI (n=24), intravascular ultrasound-derived measures (percent atheroma volume), arterial remodeling index, and segmental lumen volumes were performed in contiguous 5-mm epicardial segments. Repeat intravascular ultrasound imaging was performed after consecutive 5-minute intracoronary infusions (vehicle solution, 0.30 μg/min and 0.60 μg/min intracoronary salbutamol) to measure changes in segmental lumen volume (endothelium-dependent function). Male sex, diabetes mellitus, smoking, higher triglycerides, and lower high-density lipoprotein cholesterol were more prevalent in the NSTEMI group. Patients with NSTEMI demonstrated greater segmental percent atheroma volume (40.4±12 versus 27.5±14%, P .001), remodeling index (1.2 [1.0–1.5] versus 1.0 [0.9–1.0], P .001), and displayed less endothelium-dependent vasomotion (% change segmental lumen volume: 2.1±0.89 versus 5.1±0.89%, P=0.02) compared to patients with minimal angiographic disease. No significant difference in endothelial function between both groups was observed when controlling for plaque burden. Multivariate analysis for change in segmental lumen volume identified percent atheroma volume (β=−0.18, P=0.0004), high-sensitivity C-reactive protein mg/L (β=−3.1, P=0.03), diabetes mellitus (β=−6.9, P .0001), low-density lipoprotein cholesterol levels (β=−0.04, P=0.01), and smoking (β=–3.2, P=0.01) as independent associates. Although coronary endothelial vasoreactivity is blunted in the setting of NSTEMI, this is a reflection of the greater volume of atherosclerosis and cardiovascular risk factors. Thus, the relationship between coronary endothelium-dependent vasomotor reactivity and atheroma volume remains constant irrespective of the nature of the clinical presentation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-07-2021
DOI: 10.1161/CIRCULATIONAHA.121.055009
Abstract: High-sensitivity troponin assays are increasingly being adopted to expedite evaluation of patients with suspected acute coronary syndromes. Few direct comparisons have examined whether the enhanced performance of these assays at low concentrations leads to changes in care that improves longer-term outcomes. This study evaluated late outcomes of participants managed under an unmasked 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol compared with a 0/3-hour masked hs-cTnT protocol. We conducted a multicenter prospective patient-level randomized comparison of care informed by unmasked 0/1-hour hs-cTnT protocol (reported to ng/L) versus standard practice masked hs-cTnT testing (reported to ≤29 ng/L) assessed at 0/3 hours and followed participants for 12 months. Participants included were those presenting to metropolitan emergency departments with suspected acute coronary syndromes, without ECG evidence of coronary ischemia. The primary end point was time to all-cause death or myocardial infarction using Cox proportional hazards models adjusted for clustering within hospitals. Between August 2015 and April 2019, we randomized 3378 participants, of whom 108 withdrew, resulting in 12-month follow-up for 3270 participants (masked: 1632 unmasked: 1638). Among these, 2993 (91.5%) had an initial troponin concentration of ≤29 ng/L. Deployment of the 0/1-hour hs-cTnT protocol was associated with reductions in functional testing. Over 12-month follow-up, there was no difference in invasive coronary angiography (0/1-hour unmasked: 232/1638 [14.2%] 0/3-hour masked: 202/1632 [12.4%] P =0.13), although an increase was seen among patients with hs-cTnT levels within the masked range (0/1-hour unmasked arm: 168/1507 [11.2%] 0/3-hour masked arm: 124/1486 [8.3%] P =0.010). By 12 months, all-cause death and myocardial infarction did not differ between study arms overall (0/1-hour: 82/1638 [5.0%] versus 0/3-hour: 62/1632 [3.8%] hazard ratio, 1.32 [95% CI, 0.95–1.83] P =0.10). Among participants with initial troponin T concentrations ≤29 ng/L, unmasked hs-cTnT reporting was associated with an increase in death or myocardial infarction (0/1-hour: 55/1507 [3.7%] versus 0/3-hour: 34/1486 [2.3%] hazard ratio, 1.60 [95% CI, 1.05–2.46] P =0.030). Unmasked hs-cTnT reporting deployed within a 0/1-hour protocol did not reduce ischemic events over 12-month follow-up. Changes in practice associated with the implementation of this protocol may be associated with an increase in death and myocardial infarction among those with newly identified troponin elevations. URL: www.anzctr.org.au Unique identifier: ACTRN12615001379505.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.HLC.2016.03.013
Abstract: Transcatheter aortic valve replacement (TAVR) has become an established treatment for patients with severe aortic stenosis and high surgical risk. Ten years of technological advances in valve structure and delivery systems alongside growing operator and centre experience has opened TAVR implantation to an increasingly broad range of patients. The extension to off-label use however needs careful consideration and monitoring. Through discussion of our case involving an inoperable 24-year-old male with severe aortic regurgitation (AR), we highlight the need for an experienced and multidisciplinary team, together with early and extensive patient and family disclosure and engagement, prior to considering any off-label application of TAVR.
Publisher: American Physiological Society
Date: 10-2019
DOI: 10.1152/AJPHEART.00067.2019
Abstract: A large body of evidence demonstrates an independent association between arterial stiffness and prospective risk of cardiovascular events. A reduction in coronary perfusion is presumed to underscore this association however, studies confirming this are lacking. This study compared invasive measures of coronary blood flow (CBF) with cardiac magnetic resonance (CMR)-derived aortic distensibility (AD). Following coronary angiography, a Doppler FloWire and infusion microcatheter were advanced into the study vessel. Average peak velocity (APV) was acquired at baseline and following intracoronary adenosine to derive coronary flow velocity reserve (CFVR = hyperemic APV/resting APV) and CBF [π × (diameter) 2 × APV × 0.125]. Following angiography, patients underwent CMR to evaluate distensibility at the ascending aorta (AA), proximal descending aorta (PDA) and distal descending aorta (DDA). Fifteen participants (53 ± 13 yr) with minor epicardial disease (maximum stenosis %) were enrolled. Resting CBF was 44.1 ± 11.9 mL/min, hyperemic CBF was 143.8 ± 37.4 mL/min, and CFVR was 3.15 ± 0.48. AD was 3.89 ± 1.72·10 −3 mmHg −1 at the AA, 4.08 ± 1.80·10 −3 mmHg −1 at the PDA, and 4.42 ± 1.67·10 −3 mmHg −1 at the DDA. All levels of distensibility correlated with resting CBF ( R 2 = 0.350–0.373, P 0.05), hyperemic CBF ( R 2 = 0.453–0.464, P 0.01), and CFVR ( R 2 = 0.442–0.511, P 0.01). This study demonstrates that hyperemic and, to a lesser extent resting CBF, are significantly associated with measures of aortic stiffness in patients with only minor angiographic disease. These findings provide further in vivo support for the observed prognostic capacity of large artery function in cardiovascular event prediction. NEW & NOTEWORTHY Cardiac magnetic resonance-derived aortic distensibility is associated with invasive measures of coronary blood flow. Large artery function is more strongly correlated with hyperemic than resting blood flow. Increased stiffness may represent a potential target for novel antianginal medications.
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: 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: 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: 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: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.HLC.2019.04.014
Abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAb) have progressed from showing marked low density lipoprotein cholesterol lowering in early phase trials through to reducing cardiovascular events in large clinical outcome trials. Recently in Australia, the indication for evolocumab has been expanded to include both heterozygous and homozygous familial hypercholesterolaemia under the Pharmaceutical Benefits Scheme (PBS). With prices remaining high currently their use in non-familial hypercholesterolaemia in Australia remains by private prescription only at this stage. This manuscript summarises the major outcomes trials of the PCSK9 mAbs and the secondary analyses that have assessed their benefits in high risk patient groups, and describes the consensus of authors on which patients would most likely benefit from PCSK9 mAb therapy.
Publisher: Oxford University Press (OUP)
Date: 24-12-2016
DOI: 10.1093/EHJCI/JEW212
Abstract: We evaluated the utility of computerized tomography (CT) with respect to sizing work-up for percutaneous left atrial appendage (LAA) closure, and implications for procedural safety and outcomes. Contrast-enhanced multi-detector CT was routinely conducted to guide sizing for LAA closure in addition to transoesophageal echocardiography (TOE). Procedural safety and efficacy were prospectively assessed. Across 73 consecutive cases there were no device-related procedural complications, and no severe leaks. Systematic bias in orifice sizing by TOE vs. CT was significant on retrospective analysis (bias -3.0 mm vs. maximum diameter on CT bias -1.1 mm vs. mean diameter on CT). Importantly, this translated to an altered device size selection in more than half of all cases, and median size predicted by CT was one interval greater than that predicted by TOE (27 mm vs. 24 mm). Of particular note, gross sizing error by TOE vs. CT was observed in at least 3.4% of cases. Degree of discrepancy between TOE and CT was correlated with LAA orifice eccentricity, orifice size, and left atrial volume. Mean orifice size by CT had the greatest utility for final Watchman device-size selection. In this single-centre registry of LAA closure, routine incorporation of CT was associated with excellent outcomes for procedural safety and absence of major residual leak. Mean orifice size may be preferable to maximum orifice size. A particular value of CT may be the detection and subsequent avoidance of gross sizing error by 2D TOE that occurs in a small but important proportion of cases.
Publisher: Elsevier BV
Date: 05-2015
Publisher: Springer Science and Business Media LLC
Date: 08-2019
DOI: 10.1007/S12026-019-09091-X
Abstract: Low levels of IgM auto-antibodies have been reported in health and disease. IgM anti-neutrophil cytoplasmic antibodies (ANCA) have been reported in patients with ANCA-associated vasculitis (AAV). We sought to investigate if healthy in iduals may have IgM ANCA in their sera. The first aim of the study was to determine whether IgM ANCA was present in healthy in iduals and in patients with ANCA-associated vasculitis. The second aim was to determine what happens to IgM ANCA levels over time. The third aim was to determine whether bacterial infections affected IgM ANCA levels in non-AAV patients. Sera from healthy in iduals and patients with AAV were tested for IgM ANCA by immunofluorescence on fixed neutrophils, immunoprecipitation, Western blot and ELISA. Peripheral blood mononuclear cells were isolated and tested by ELISpot for circulating IgM ANCA B cells. To determine whether infection affected IgM ANCA levels, we studied non-AAV patients with bacterial endocarditis or Staphylococcus aureus bacteraemia and measured IgM ANCA levels over time. IgM ANCA is detectable in both healthy in iduals and patients with AAV and the titres decreased with increasing age. Circulating IgM ANCA B cells were identified by ELISpot. In the presence of infection, we could not find a significant change in IgM ANCA levels. We report the presence of low-level specific IgM ANCA in the sera of healthy in iduals and in patients with ANCA-associated vasculitis. Bacterial infection did not affect the level of IgM ANCA in this small study.
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: 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: Wiley
Date: 14-03-2014
DOI: 10.1111/NEP.12192
Abstract: Adenoviruses are common pathogens that have the potential to cause opportunistic infections with significant morbidity and mortality in immunocompromised hosts. The significance of adenoviral infection and disease is incompletely known in the setting of kidney transplantation. Reported adenovirus infections in renal transplant recipients have typically manifested as haemorrhagic cystitis and tubulointerstitial nephritis. Pneumonia, hepatitis and enteritis are often seen in other solid organ recipients. However, disseminated or severe adenovirus infections, including fatal cases, have been described in renal transplant recipients. There is uncertainty regarding monitoring and treatment of this virus. Although not supported by randomized clinical trials, cidofovir is used for the treatment of adenovirus disease not responding to reduction of immunosuppression. We present a case series of 2 patients with disseminated adenovirus infection in our centre who presented at different times from the time of transplantation.
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: BMJ
Date: 27-01-2020
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: Ovid Technologies (Wolters Kluwer Health)
Date: 26-11-2019
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.IJCARD.2012.05.051
Abstract: The high diagnostic accuracy of adenosine stress cardiac magnetic resonance (AS-CMR) for detecting coronary artery stenoses, with high sensitivity and specificity, is well documented. Prognostic data, particularly in non-low risk study populations and for greater than 12 months of follow up, is however lacking or variable in its findings. We present prognostic data, in an intermediate cardiovascular risk cohort undergoing adenosine stress perfusion CMR, over approximately 2 years of follow up. The study population comprised 362 patients referred for a clinically indicated stress CMR and included patients with proven coronary artery disease (CAD n=157) or unknown CAD status, yet an intermediate cardiovascular risk profile (n=205). Perfusion imaging was performed at stress (adenosine 140 μg/kg/min) and rest on a 1.5 T system. Patient records and state-wide hospital databases were reviewed. Major adverse cardiac events--death, myocardial infarction, revascularisation or ischaemic hospitalisation--were evaluated over a median follow up of 22 months. Of the 362 cases, 90 had a stress perfusion CMR positive for ischaemia and experienced a MACE rate of 24%. Of the 272 negative CMR scans, 225 were also negative for late gadolinium enhancement, and in this group MACE was encountered in only 6 (2.7%) patients. Accordingly a negative stress CMR afforded a freedom from MACE of 97.3%. Freedom from death/myocardial infarction was 99.6%. In patients with confirmed coronary artery disease or at intermediate risk for cardiovascular events, a negative stress perfusion CMR is associated with an excellent prognosis over nearly 2 years of follow up.
Publisher: Informa UK Limited
Date: 08-2017
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.HLC.2011.07.007
Abstract: Coronary spasm is increasingly recognised as an important aetiological mechanism causing myocardial ischaemia. Occasionally cases present with evidence of ST segment elevation myocardial infarction, usually secondary to spasm confined to a solitary coronary artery. We present the rare and life-threatening case of severe coronary spasm afflicting all three major epicardial arteries simultaneously. It describes the difficult emergency scenario and ongoing management dilemmas encountered by physicians confronted with multivessel coronary spasm. Moreover we discuss the malignant prognosis associated with this ailment and describe the potential insights provided by cardiac magnetic resonance imaging that might identify those at greatest risk after the index event.
Publisher: Springer Science and Business Media LLC
Date: 12-12-2019
DOI: 10.1007/S12265-019-09942-W
Abstract: Androgen deprivation therapy (ADT) has been the cornerstone of prostate cancer treatment. ADT delays cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these established benefits, the extended duration of therapy comes with known side effects. Furthermore, research from the past decade has generated increased awareness for more potentially lethal cardiometabolic consequences of ADT. In this review, we explore the relationship between ADT and cardiometabolic effects. Current literature on this complex relationship remains conflicting, due to a variety of factors, including study design (randomized vs. observational), treatment decision-making, and patient factors. Looking to the future, a combination of well-designed, randomized controlled trials and high-quality, real-world evidence are needed to definitely establish any ADT cardiovascular safety signal and to evaluate the efficacy of potential screening and therapeutic interventions. Furthermore, a collaborative, integrated approach among all health care professionals is critical to accurately delineate patients' potential risk/benefit treatment options.
No related grants have been discovered for Adam Nelson.