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Papers by Diễm Đinh

Research paper thumbnail of Incidence and Predictors of Unplanned Hospital Readmission after Percutaneous Coronary Intervention

Journal of Clinical Medicine, 2020

Unplanned readmissions to hospital after percutaneous coronary intervention (PCI) pose a signific... more Unplanned readmissions to hospital after percutaneous coronary intervention (PCI) pose a significant burden to the healthcare system and are potentially preventable. In this study, we sought to determine the incidence of, and risk factors for, unplanned hospital readmissions within 30 days following PCI. We prospectively collected data on 28,488 patients undergoing PCI between 2013 and 2019, who were enrolled in the state-wide multi-centre Victorian Cardiac Outcomes Registry. Patients’ data were then linked to data from the Victorian Department of Health administrative database that records statewide hospital admissions. Disease diagnosis codes were used to identify cause of readmission. Patients who had an unplanned readmission were further divided into those who had a cardiac vs. non-cardiac cause for readmission. Overall, 3059 patients (10.7%) had an unplanned hospital readmission within 30 days of PCI, of which 1848 patients (60.4%) were readmitted for primarily cardiac diagnose...

Research paper thumbnail of Bleeding Severity in Percutaneous Coronary Intervention (PCI) and its Impact on short-Term Clinical Outcomes

Heart, Lung and Circulation, 2019

Aims: To review the complications, mortality and destination therapy of patients undergoing ballo... more Aims: To review the complications, mortality and destination therapy of patients undergoing balloon aortic valvuloplasty (BAV) in the era of transcatheter aortic valve implantation (TAVI). Methods: A systematic literature search identified journal articles reporting the outcomes of adult patients undergoing BAV procedures. Cohorts of 50 or more patients undergoing BAV between January 2002 and May 2018 were included in the review. Patient baseline characteristics, surgical risk scores, complications, short-and long-term mortality and reported destination therapy were extracted and aggregated, with estimated mean and standard deviation weighted by cohort size. Results: A total of 29 papers were included, describing the outcomes of 9,602 patients. The mean age of the patient cohorts was 82.3 ± 1.3 years. 51.6% of the patients were female and the mean STS score was 12.3 ± 3.2. The rates of stroke, myocardial infarction, major vascular complications and greater than BARC 2 bleeding post-BAV were 1.2% ± 0.7, 1.2% ± 1.5, 2.4% ± 1.1 and 8.9% ± 2.2 respectively. Periprocedural and intrahospital mortality rates were 1.7% ± 2.8 and 7.0% ± 4.2. Mortality rates at 30 days and 12 months were 7.7% ± 6.0 and 34.4% ± 12.7. Reported rates of patients undergoing TAVI, surgical aortic valve replacement or medical management post-BAV were 17.2% ± 12.1, 4.9% ± 4.0 and 77.0% ± 14.0. Conclusions: Short and medium-term outcomes following BAV are similar to contemporary cohorts undergoing TAVI. The vast majority of patients do not proceed to further intervention, with BAV being their destination therapy. The clinical and economic impact of such practice in the era of TAVI requires further study.

Research paper thumbnail of Delays in primary percutaneous coronary treatment for patients with ST‐elevation myocardial infarction

Medical Journal of Australia, 2018

Research paper thumbnail of Comparison of Short-term Clinical Outcomes of Proximal Versus Non-Proximal Culprit Lesion Location in Patients Treated with Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction

Heart, Lung and Circulation, 2017

Abstracts S73 median (IQR) (66 min, 43-79 vs. 67 min, 44-96, p = 0.9), leading to shorter symptom... more Abstracts S73 median (IQR) (66 min, 43-79 vs. 67 min, 44-96, p = 0.9), leading to shorter symptom-to-balloon time, median (IQR) (184 min, 132-239 vs. 194 min, 141-291, p = 0.051). There were no significant differences between outcomes for in-hospital, 30-day, 12-months and (NDI-linked) long-term mortality between the two groups. ST was not an independent predictor of 30-day MACE on multivariate analysis (HR 0.8, CI 0.4-1.8, p = 0.75). Patients presenting with STEMI caused by definite ST had similar outcomes to those caused by de novo lesions. A shorter STDT may represent earlier recognition of symptoms in the ST group and possibly contributed to their similar outcome with the de novo group.

Research paper thumbnail of Prevalence and outcomes of trans-radial access for percutaneous coronary intervention in contemporary practise

International Journal of Cardiology, 2016

Background: Trans-radial access for percutaneous coronary intervention (PCI) has been associated ... more Background: Trans-radial access for percutaneous coronary intervention (PCI) has been associated with lower vascular complication rates and improved outcomes. We assessed the current uptake of trans-radial PCI in Victoria, Australia, and evaluated if patients were selected according to baseline bleeding risk in contemporary clinical practise, and compared selected clinical outcomes. Methods: PCI data of all patients between 1st January 2013 and 31st December 2014 were analysed using The Victorian Cardiac Outcomes Registry (VCOR). Propensity-matched analysis was performed to compare the clinical outcomes. Results: 11,711 procedures were analysed. The femoral route was the predominant access site (66%). Patients undergoing trans-radial access PCI were younger (63.9 ± 11.6 vs. 67.2 ± 11.8; p b 0.001), had a higher BMI (28.9 ± 5.5 vs. 28.5 ± 5.2; p b 0.001), more likely to be male (80.0 vs. 74.9%;p b 0.001), less likely to have presented with cardiogenic shock (0.9 vs. 2.8%; p b 0.001) or have the following comorbidities: diabetes (19.8 vs. 23.1%; p b 0.001), peripheral vascular disease (2.9 vs. 4.3%; p = 0.005) or renal impairment (13.6 vs. 22.1%; p b 0.001). The radial group had less bleeding events (3.2 vs. 4.6%; p b 0.001) and shorter hospital length of stay (3.1 ± 4.7 vs. 3.3 ± 3.9; p = 0.006). There was no significant difference in mortality (1.0 vs. 1.4%; p = 0.095). Conclusions: Trans-femoral approach remains the dominant access site for PCI in Victoria. The choice of route does not appear to be selected by consideration of bleeding risk. The radial route is associated with improved clinical outcomes of reduced bleeding and length of stay consistent with previous findings, and this supports the efficacy and safety of trans-radial PCI in real-world clinical practise.

Research paper thumbnail of Angiotensin AT4 receptors in the normal human prostate and benign prostatic hyperplasia

Molecular and Cellular Endocrinology, 2001

Research paper thumbnail of In vivo inhibition of angiotensin receptors in the rat kidney by candesartan cilexetil: a comparison with losartan

American Journal of Hypertension, 2000

The present study examined the in vivo effects of candesartan cilexetil compared with losartan on... more The present study examined the in vivo effects of candesartan cilexetil compared with losartan on angiotensin II (Ang II) receptor binding in the rat kidney after oral administration. Male Sprague-Dawley rats (250 to 300 g) were gavaged with candesartan cilexetil or losartan in doses of 0.1, 0.3, 1, 3, 10, or 30 mg/kg, or corresponding vehicle. Rats were killed at 0, 1, 2, 8, or 24 h after drug administration, trunk blood collected, and kidneys removed. The effects of candesartan cilexetil and losartan on Ang II receptor binding were determined by quantitative in vitro autoradiography using the radioligand [ 125 I]-[Sar 1 ,Ile 8 ] Ang II. Ang II receptor binding in the kidney was mainly due to AT 1 receptors with high levels of binding localized to the inner stripe of the outer medulla and glomeruli in cortical regions. Candesartan cilexetil (0.1 to 30 mg/kg) inhibited Ang II receptor binding to all anatomical sites of the kidney, in a dose-dependent manner. Losartan (0.1 to 30 mg/kg) also produced dosedependent inhibition of Ang II receptor binding but was approximately 10-to 30-fold less potent than candesartan cilexetil. Inhibition of Ang II receptor binding was near maximal about 1 h after administration of candesartan cilexetil (10 mg/kg) or losartan (10 mg/kg), with both drugs producing persistent blockade at 24 h despite plasma renin activity and plasma drug concentrations returning to near normal levels. In vitro, candesartan, losartan, and EXP3174 (1 ؋ ؋ 10 ؊ ؊10 to 1 ؋ ؋ 10 ؊ ؊5 mol/L) displaced [ 125 I]-[Sar 1 ,Ile 8 ] Ang II binding from AT 1 receptors in the kidney in a concentration-dependent manner with a rank order of potency of candesartan > > EXP3174 > > losartan. The concentration required to displace 50% of radioligand binding (IC 50 ) by candesartan, EXP3174, and losartan was 0.9 ؎ ؎ 0.1 nmol/L, 3.4 ؎ ؎ 0.4 nmol/L, and 8.9 ؎ ؎ 1.1 nmol/L, respectively. In conclusion, the findings of the present study suggest that candesartan cilexetil is more potent than losartan in antagonizing AT 1 receptors in the kidney in vivo. Nonetheless, both candesartan cilexetil and losartan produce rapid, complete, and sustained blockade of AT 1 receptors in the rat kidney. Tissue blockade of Ang II receptors in target organs, such as the kidney, may contribute to the beneficial effects of Ang II receptor antagonists as antihypertensive agents.

Research paper thumbnail of Preoperative atrial fibrillation is an independent predictor of worse early and late outcomes after isolated coronary artery bypass graft surgery

Journal of cardiology, Jan 3, 2014

To evaluate the impact of preoperative atrial fibrillation (pre-op AF) on early and late mortalit... more To evaluate the impact of preoperative atrial fibrillation (pre-op AF) on early and late mortality after isolated coronary artery bypass graft (CABG) surgery. Data obtained prospectively between June 2001 and December 2009 by the Australasian Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database Program were retrospectively analyzed. Patients who underwent concomitant atrial arrhythmia surgery/ablation were excluded. Demographic and operative data were compared between patients with and without pre-op AF. The independent association of pre-op AF on early mortality, perioperative complications, and late mortality was determined. Isolated CABG surgery was performed in 21,534 patients; 1312 (6.1%) presented with pre-op AF. Pre-op AF patients were older (mean age, 71 years vs. 65 years, p<0.001) and had more comorbidities reflected in a higher additive EuroSCORE (8.4±3.5 vs. 6.5±3.2, p=0.001). Even after accounting for confounding factors, however, pre-op AF was ...

Research paper thumbnail of Agonist-dependent internalization of the angiotensin II type one receptor (AT1): role of C-terminus phosphorylation in recruitment of β-arrestins

Regulatory Peptides, 2004

h-Arrestins play a role in AT 1 endocytosis by binding the cytoplasmic, C-terminus region T332 -S... more h-Arrestins play a role in AT 1 endocytosis by binding the cytoplasmic, C-terminus region T332 -S338, the major site of angiotensin II (Ang II)-induced phosphorylation. However, the processes responsible for recruiting h-arrestin to the activated receptor are poorly defined. In this study, we used CHO-K1 and HEK 293 cells expressing wild-type or mutant AT 1 to investigate two possibilities: activated AT 1 induces global relocation of h-arrestins to the plasma membrane or the phosphorylated C-terminus acts as bait to attract h-arrestins. Results obtained using high osmolarity and dominant-negative h-arrestin confirmed that internalization of AT 1 in both CHO-K1 and HEK 293 cells is predominately via clathrin-mediated endocytosis involving h-arrestin, and substitution of T332, S335, T336 and S338 with alanine to preclude phosphorylation markedly attenuated AT 1 internalization. Confocal microscopy revealed that wild-type AT 1 induced a timedependent translocation of GFP-tagged h-arrestins 1 and 2 to the cell surface. In contrast, the TSTS/A mutant did not traffic h-arrestin 1 at all, and only trafficked h-arrestin 2 weakly. Results of rescue-type experiments were consistent with the idea that both h-arrestins are able to interact with the non-phosphorylated receptor, albeit with much lower affinity and h-arrestin 1 less so than h-arrestin 2. In conclusion, this study shows that the high affinity binding of h-arrestins to the phosphorylated C-terminus is the predominant mechanism of agonist-induced h-arrestin recruitment to the cell surface and AT 1 receptor.

Research paper thumbnail of Helix I of β-Arrestin Is Involved in Postendocytic Trafficking but Is Not Required for Membrane Translocation, Receptor Binding, and Internalization

Molecular Pharmacology, 2004

Research paper thumbnail of Evidence for activation of the renin–angiotensin system in the human prostate: increased angiotensin II and reduced AT1 receptor expression in benign prostatic hyperplasia

The Journal of Pathology, 2002

The expression and cellular localization of angiotensin II (Ang II) and AT1 receptor proteins wer... more The expression and cellular localization of angiotensin II (Ang II) and AT1 receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT1 receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4±0.2%, n=5 vs. BPH: 22.7±1.9%, n=5, p<0.001). However, AT1 receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4±2.2%, n=4 vs. BPH: 9.4±1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT1 receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functio...

Research paper thumbnail of Major Complications Related to the Use of Transesophageal Echocardiography in Cardiac Surgery

Journal of Cardiothoracic and Vascular Anesthesia, 2009

Research paper thumbnail of Trends in Coronary Artery Bypass Graft Surgery and Combined Aortic Valve Surgery at Auckland City Hospital

Heart, Lung and Circulation, 2010

Research paper thumbnail of Complication in octogenarians after isolated CABG surgery—Analysis of data from the ASCTS database project

Heart, Lung and Circulation, 2009

Research paper thumbnail of Comparison of the Clinical Characteristics and Mortality of Patients with Cardiogenic Shock Undergoing Coronary Artery Bypass Grafting Compared with Percutaneous Coronary Intervention—Insights from Two Multi-centre Registries

Heart, Lung and Circulation, 2008

Research paper thumbnail of Does Prior Percutaneous Coronary Intervention Adversely Affect Early and Long-term Survival After Coronary Artery Surgery?

Heart, Lung and Circulation, 2009

Objectives: To determine the association between previous percutaneous coronary intervention (PCI... more Objectives: To determine the association between previous percutaneous coronary intervention (PCI) and results after coronary artery bypass graft surgery (CABG). Background: Increasing numbers of patients undergoing CABG have previously undergone PCI. Methods: We analyzed consecutive first-time isolated CABG procedures within the Australasian Society of Cardiac and Thoracic Surgeons Database from June 2001 to May 2008. Logistic regression and propensity score analyses were used to assess the risk-adjusted impact of prior PCI on in-hospital mortality and major adverse cardiac events. Cox regression model was used to assess the effect of prior PCI on mid-term survival. Results: Of 13,184 patients who underwent CABG, 11,727 had no prior PCI and 1,457 had prior PCI. Mean follow-up was 3.3 ± 2.1 years. Patients without prior PCI had a higher EuroSCORE value (4.4 ± 3.3 vs. 3.6 ± 3.0, p &lt; 0.001), were older, and more likely to have left main stem stenosis and recent myocardial infarction. There was no difference in unadjusted in-hospital mortality (1.65% vs. 1.55%, p = 0.78) or major adverse cardiac events (3.0% vs. 3.0%, p = 0.99) between patients with or without prior PCI. After adjustment, prior PCI was not a predictor of in-hospital (odds ratio: 1.22, 95% confidence interval [CI]: 0.76 to 2.0, p = 0.41) or mid-term mortality at 6-year follow-up (hazard ratio: 0.94, 95% CI: 0.75 to 1.18, p = 0.62). Conclusions: In this large registry study, prior PCI was not associated with increased short- or mid-term mortality after CABG. Good outcomes can be obtained in the group of patients undergoing CABG who have had previous PCI. © 2009 American College of Cardiology Foundation

Research paper thumbnail of The AusScore—A Validated Model for Predicting Outcome Following Isolated Coronary Bypass Graft Procedures in Australia

Heart, Lung and Circulation, 2007

Research paper thumbnail of Trends in CABG Surgery in Victoria 2001–2006—Findings from the ASCTS Database Project

Heart, Lung and Circulation, 2007

Research paper thumbnail of Progress Towards a National Cardiac Procedure Database—Development of the Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) and Melbourne Interventional Group (MIG) Registries

Heart, Lung and Circulation, 2011

Since the call for a National Cardiac Procedures Database in 2001, much work has been accomplishe... more Since the call for a National Cardiac Procedures Database in 2001, much work has been accomplished in both cardiac surgery and interventional cardiology in an attempt to establish a unified, systematic approach to data collection, defining a common minimum dataset pertinent to the Australian context, and instituting quality control measures to ensure integrity and privacy of data. In this paper we outline the aims of the Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) and the Melbourne Interventional Group (MIG) registries, and propose a comprehensive set of standardised data elements and their definitions to facilitate transparency in data collection, consistency between these and other data sets, and encourage ongoing peer-review. The aims are to improve outcomes for patients by determining key performance indicators and standards of performance for hospital units, to allow estimation of procedural risks and likelihood of outcomes for patients, and to report outcomes to relevant stake-holders and the public.

Research paper thumbnail of Predictors of 1-Year Mortality of Patients Undergoing Coronary Artery Bypass Grafting (CABG) Compared to Percutaneous Coronary Intervention (PCI)—Insights From Two Large Multi-centre Australian Registries

Heart, Lung and Circulation, 2008

Research paper thumbnail of Incidence and Predictors of Unplanned Hospital Readmission after Percutaneous Coronary Intervention

Journal of Clinical Medicine, 2020

Unplanned readmissions to hospital after percutaneous coronary intervention (PCI) pose a signific... more Unplanned readmissions to hospital after percutaneous coronary intervention (PCI) pose a significant burden to the healthcare system and are potentially preventable. In this study, we sought to determine the incidence of, and risk factors for, unplanned hospital readmissions within 30 days following PCI. We prospectively collected data on 28,488 patients undergoing PCI between 2013 and 2019, who were enrolled in the state-wide multi-centre Victorian Cardiac Outcomes Registry. Patients’ data were then linked to data from the Victorian Department of Health administrative database that records statewide hospital admissions. Disease diagnosis codes were used to identify cause of readmission. Patients who had an unplanned readmission were further divided into those who had a cardiac vs. non-cardiac cause for readmission. Overall, 3059 patients (10.7%) had an unplanned hospital readmission within 30 days of PCI, of which 1848 patients (60.4%) were readmitted for primarily cardiac diagnose...

Research paper thumbnail of Bleeding Severity in Percutaneous Coronary Intervention (PCI) and its Impact on short-Term Clinical Outcomes

Heart, Lung and Circulation, 2019

Aims: To review the complications, mortality and destination therapy of patients undergoing ballo... more Aims: To review the complications, mortality and destination therapy of patients undergoing balloon aortic valvuloplasty (BAV) in the era of transcatheter aortic valve implantation (TAVI). Methods: A systematic literature search identified journal articles reporting the outcomes of adult patients undergoing BAV procedures. Cohorts of 50 or more patients undergoing BAV between January 2002 and May 2018 were included in the review. Patient baseline characteristics, surgical risk scores, complications, short-and long-term mortality and reported destination therapy were extracted and aggregated, with estimated mean and standard deviation weighted by cohort size. Results: A total of 29 papers were included, describing the outcomes of 9,602 patients. The mean age of the patient cohorts was 82.3 ± 1.3 years. 51.6% of the patients were female and the mean STS score was 12.3 ± 3.2. The rates of stroke, myocardial infarction, major vascular complications and greater than BARC 2 bleeding post-BAV were 1.2% ± 0.7, 1.2% ± 1.5, 2.4% ± 1.1 and 8.9% ± 2.2 respectively. Periprocedural and intrahospital mortality rates were 1.7% ± 2.8 and 7.0% ± 4.2. Mortality rates at 30 days and 12 months were 7.7% ± 6.0 and 34.4% ± 12.7. Reported rates of patients undergoing TAVI, surgical aortic valve replacement or medical management post-BAV were 17.2% ± 12.1, 4.9% ± 4.0 and 77.0% ± 14.0. Conclusions: Short and medium-term outcomes following BAV are similar to contemporary cohorts undergoing TAVI. The vast majority of patients do not proceed to further intervention, with BAV being their destination therapy. The clinical and economic impact of such practice in the era of TAVI requires further study.

Research paper thumbnail of Delays in primary percutaneous coronary treatment for patients with ST‐elevation myocardial infarction

Medical Journal of Australia, 2018

Research paper thumbnail of Comparison of Short-term Clinical Outcomes of Proximal Versus Non-Proximal Culprit Lesion Location in Patients Treated with Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction

Heart, Lung and Circulation, 2017

Abstracts S73 median (IQR) (66 min, 43-79 vs. 67 min, 44-96, p = 0.9), leading to shorter symptom... more Abstracts S73 median (IQR) (66 min, 43-79 vs. 67 min, 44-96, p = 0.9), leading to shorter symptom-to-balloon time, median (IQR) (184 min, 132-239 vs. 194 min, 141-291, p = 0.051). There were no significant differences between outcomes for in-hospital, 30-day, 12-months and (NDI-linked) long-term mortality between the two groups. ST was not an independent predictor of 30-day MACE on multivariate analysis (HR 0.8, CI 0.4-1.8, p = 0.75). Patients presenting with STEMI caused by definite ST had similar outcomes to those caused by de novo lesions. A shorter STDT may represent earlier recognition of symptoms in the ST group and possibly contributed to their similar outcome with the de novo group.

Research paper thumbnail of Prevalence and outcomes of trans-radial access for percutaneous coronary intervention in contemporary practise

International Journal of Cardiology, 2016

Background: Trans-radial access for percutaneous coronary intervention (PCI) has been associated ... more Background: Trans-radial access for percutaneous coronary intervention (PCI) has been associated with lower vascular complication rates and improved outcomes. We assessed the current uptake of trans-radial PCI in Victoria, Australia, and evaluated if patients were selected according to baseline bleeding risk in contemporary clinical practise, and compared selected clinical outcomes. Methods: PCI data of all patients between 1st January 2013 and 31st December 2014 were analysed using The Victorian Cardiac Outcomes Registry (VCOR). Propensity-matched analysis was performed to compare the clinical outcomes. Results: 11,711 procedures were analysed. The femoral route was the predominant access site (66%). Patients undergoing trans-radial access PCI were younger (63.9 ± 11.6 vs. 67.2 ± 11.8; p b 0.001), had a higher BMI (28.9 ± 5.5 vs. 28.5 ± 5.2; p b 0.001), more likely to be male (80.0 vs. 74.9%;p b 0.001), less likely to have presented with cardiogenic shock (0.9 vs. 2.8%; p b 0.001) or have the following comorbidities: diabetes (19.8 vs. 23.1%; p b 0.001), peripheral vascular disease (2.9 vs. 4.3%; p = 0.005) or renal impairment (13.6 vs. 22.1%; p b 0.001). The radial group had less bleeding events (3.2 vs. 4.6%; p b 0.001) and shorter hospital length of stay (3.1 ± 4.7 vs. 3.3 ± 3.9; p = 0.006). There was no significant difference in mortality (1.0 vs. 1.4%; p = 0.095). Conclusions: Trans-femoral approach remains the dominant access site for PCI in Victoria. The choice of route does not appear to be selected by consideration of bleeding risk. The radial route is associated with improved clinical outcomes of reduced bleeding and length of stay consistent with previous findings, and this supports the efficacy and safety of trans-radial PCI in real-world clinical practise.

Research paper thumbnail of Angiotensin AT4 receptors in the normal human prostate and benign prostatic hyperplasia

Molecular and Cellular Endocrinology, 2001

Research paper thumbnail of In vivo inhibition of angiotensin receptors in the rat kidney by candesartan cilexetil: a comparison with losartan

American Journal of Hypertension, 2000

The present study examined the in vivo effects of candesartan cilexetil compared with losartan on... more The present study examined the in vivo effects of candesartan cilexetil compared with losartan on angiotensin II (Ang II) receptor binding in the rat kidney after oral administration. Male Sprague-Dawley rats (250 to 300 g) were gavaged with candesartan cilexetil or losartan in doses of 0.1, 0.3, 1, 3, 10, or 30 mg/kg, or corresponding vehicle. Rats were killed at 0, 1, 2, 8, or 24 h after drug administration, trunk blood collected, and kidneys removed. The effects of candesartan cilexetil and losartan on Ang II receptor binding were determined by quantitative in vitro autoradiography using the radioligand [ 125 I]-[Sar 1 ,Ile 8 ] Ang II. Ang II receptor binding in the kidney was mainly due to AT 1 receptors with high levels of binding localized to the inner stripe of the outer medulla and glomeruli in cortical regions. Candesartan cilexetil (0.1 to 30 mg/kg) inhibited Ang II receptor binding to all anatomical sites of the kidney, in a dose-dependent manner. Losartan (0.1 to 30 mg/kg) also produced dosedependent inhibition of Ang II receptor binding but was approximately 10-to 30-fold less potent than candesartan cilexetil. Inhibition of Ang II receptor binding was near maximal about 1 h after administration of candesartan cilexetil (10 mg/kg) or losartan (10 mg/kg), with both drugs producing persistent blockade at 24 h despite plasma renin activity and plasma drug concentrations returning to near normal levels. In vitro, candesartan, losartan, and EXP3174 (1 ؋ ؋ 10 ؊ ؊10 to 1 ؋ ؋ 10 ؊ ؊5 mol/L) displaced [ 125 I]-[Sar 1 ,Ile 8 ] Ang II binding from AT 1 receptors in the kidney in a concentration-dependent manner with a rank order of potency of candesartan > > EXP3174 > > losartan. The concentration required to displace 50% of radioligand binding (IC 50 ) by candesartan, EXP3174, and losartan was 0.9 ؎ ؎ 0.1 nmol/L, 3.4 ؎ ؎ 0.4 nmol/L, and 8.9 ؎ ؎ 1.1 nmol/L, respectively. In conclusion, the findings of the present study suggest that candesartan cilexetil is more potent than losartan in antagonizing AT 1 receptors in the kidney in vivo. Nonetheless, both candesartan cilexetil and losartan produce rapid, complete, and sustained blockade of AT 1 receptors in the rat kidney. Tissue blockade of Ang II receptors in target organs, such as the kidney, may contribute to the beneficial effects of Ang II receptor antagonists as antihypertensive agents.

Research paper thumbnail of Preoperative atrial fibrillation is an independent predictor of worse early and late outcomes after isolated coronary artery bypass graft surgery

Journal of cardiology, Jan 3, 2014

To evaluate the impact of preoperative atrial fibrillation (pre-op AF) on early and late mortalit... more To evaluate the impact of preoperative atrial fibrillation (pre-op AF) on early and late mortality after isolated coronary artery bypass graft (CABG) surgery. Data obtained prospectively between June 2001 and December 2009 by the Australasian Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database Program were retrospectively analyzed. Patients who underwent concomitant atrial arrhythmia surgery/ablation were excluded. Demographic and operative data were compared between patients with and without pre-op AF. The independent association of pre-op AF on early mortality, perioperative complications, and late mortality was determined. Isolated CABG surgery was performed in 21,534 patients; 1312 (6.1%) presented with pre-op AF. Pre-op AF patients were older (mean age, 71 years vs. 65 years, p<0.001) and had more comorbidities reflected in a higher additive EuroSCORE (8.4±3.5 vs. 6.5±3.2, p=0.001). Even after accounting for confounding factors, however, pre-op AF was ...

Research paper thumbnail of Agonist-dependent internalization of the angiotensin II type one receptor (AT1): role of C-terminus phosphorylation in recruitment of β-arrestins

Regulatory Peptides, 2004

h-Arrestins play a role in AT 1 endocytosis by binding the cytoplasmic, C-terminus region T332 -S... more h-Arrestins play a role in AT 1 endocytosis by binding the cytoplasmic, C-terminus region T332 -S338, the major site of angiotensin II (Ang II)-induced phosphorylation. However, the processes responsible for recruiting h-arrestin to the activated receptor are poorly defined. In this study, we used CHO-K1 and HEK 293 cells expressing wild-type or mutant AT 1 to investigate two possibilities: activated AT 1 induces global relocation of h-arrestins to the plasma membrane or the phosphorylated C-terminus acts as bait to attract h-arrestins. Results obtained using high osmolarity and dominant-negative h-arrestin confirmed that internalization of AT 1 in both CHO-K1 and HEK 293 cells is predominately via clathrin-mediated endocytosis involving h-arrestin, and substitution of T332, S335, T336 and S338 with alanine to preclude phosphorylation markedly attenuated AT 1 internalization. Confocal microscopy revealed that wild-type AT 1 induced a timedependent translocation of GFP-tagged h-arrestins 1 and 2 to the cell surface. In contrast, the TSTS/A mutant did not traffic h-arrestin 1 at all, and only trafficked h-arrestin 2 weakly. Results of rescue-type experiments were consistent with the idea that both h-arrestins are able to interact with the non-phosphorylated receptor, albeit with much lower affinity and h-arrestin 1 less so than h-arrestin 2. In conclusion, this study shows that the high affinity binding of h-arrestins to the phosphorylated C-terminus is the predominant mechanism of agonist-induced h-arrestin recruitment to the cell surface and AT 1 receptor.

Research paper thumbnail of Helix I of β-Arrestin Is Involved in Postendocytic Trafficking but Is Not Required for Membrane Translocation, Receptor Binding, and Internalization

Molecular Pharmacology, 2004

Research paper thumbnail of Evidence for activation of the renin–angiotensin system in the human prostate: increased angiotensin II and reduced AT1 receptor expression in benign prostatic hyperplasia

The Journal of Pathology, 2002

The expression and cellular localization of angiotensin II (Ang II) and AT1 receptor proteins wer... more The expression and cellular localization of angiotensin II (Ang II) and AT1 receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT1 receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4±0.2%, n=5 vs. BPH: 22.7±1.9%, n=5, p<0.001). However, AT1 receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4±2.2%, n=4 vs. BPH: 9.4±1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT1 receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functio...

Research paper thumbnail of Major Complications Related to the Use of Transesophageal Echocardiography in Cardiac Surgery

Journal of Cardiothoracic and Vascular Anesthesia, 2009

Research paper thumbnail of Trends in Coronary Artery Bypass Graft Surgery and Combined Aortic Valve Surgery at Auckland City Hospital

Heart, Lung and Circulation, 2010

Research paper thumbnail of Complication in octogenarians after isolated CABG surgery—Analysis of data from the ASCTS database project

Heart, Lung and Circulation, 2009

Research paper thumbnail of Comparison of the Clinical Characteristics and Mortality of Patients with Cardiogenic Shock Undergoing Coronary Artery Bypass Grafting Compared with Percutaneous Coronary Intervention—Insights from Two Multi-centre Registries

Heart, Lung and Circulation, 2008

Research paper thumbnail of Does Prior Percutaneous Coronary Intervention Adversely Affect Early and Long-term Survival After Coronary Artery Surgery?

Heart, Lung and Circulation, 2009

Objectives: To determine the association between previous percutaneous coronary intervention (PCI... more Objectives: To determine the association between previous percutaneous coronary intervention (PCI) and results after coronary artery bypass graft surgery (CABG). Background: Increasing numbers of patients undergoing CABG have previously undergone PCI. Methods: We analyzed consecutive first-time isolated CABG procedures within the Australasian Society of Cardiac and Thoracic Surgeons Database from June 2001 to May 2008. Logistic regression and propensity score analyses were used to assess the risk-adjusted impact of prior PCI on in-hospital mortality and major adverse cardiac events. Cox regression model was used to assess the effect of prior PCI on mid-term survival. Results: Of 13,184 patients who underwent CABG, 11,727 had no prior PCI and 1,457 had prior PCI. Mean follow-up was 3.3 ± 2.1 years. Patients without prior PCI had a higher EuroSCORE value (4.4 ± 3.3 vs. 3.6 ± 3.0, p &lt; 0.001), were older, and more likely to have left main stem stenosis and recent myocardial infarction. There was no difference in unadjusted in-hospital mortality (1.65% vs. 1.55%, p = 0.78) or major adverse cardiac events (3.0% vs. 3.0%, p = 0.99) between patients with or without prior PCI. After adjustment, prior PCI was not a predictor of in-hospital (odds ratio: 1.22, 95% confidence interval [CI]: 0.76 to 2.0, p = 0.41) or mid-term mortality at 6-year follow-up (hazard ratio: 0.94, 95% CI: 0.75 to 1.18, p = 0.62). Conclusions: In this large registry study, prior PCI was not associated with increased short- or mid-term mortality after CABG. Good outcomes can be obtained in the group of patients undergoing CABG who have had previous PCI. © 2009 American College of Cardiology Foundation

Research paper thumbnail of The AusScore—A Validated Model for Predicting Outcome Following Isolated Coronary Bypass Graft Procedures in Australia

Heart, Lung and Circulation, 2007

Research paper thumbnail of Trends in CABG Surgery in Victoria 2001–2006—Findings from the ASCTS Database Project

Heart, Lung and Circulation, 2007

Research paper thumbnail of Progress Towards a National Cardiac Procedure Database—Development of the Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) and Melbourne Interventional Group (MIG) Registries

Heart, Lung and Circulation, 2011

Since the call for a National Cardiac Procedures Database in 2001, much work has been accomplishe... more Since the call for a National Cardiac Procedures Database in 2001, much work has been accomplished in both cardiac surgery and interventional cardiology in an attempt to establish a unified, systematic approach to data collection, defining a common minimum dataset pertinent to the Australian context, and instituting quality control measures to ensure integrity and privacy of data. In this paper we outline the aims of the Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) and the Melbourne Interventional Group (MIG) registries, and propose a comprehensive set of standardised data elements and their definitions to facilitate transparency in data collection, consistency between these and other data sets, and encourage ongoing peer-review. The aims are to improve outcomes for patients by determining key performance indicators and standards of performance for hospital units, to allow estimation of procedural risks and likelihood of outcomes for patients, and to report outcomes to relevant stake-holders and the public.

Research paper thumbnail of Predictors of 1-Year Mortality of Patients Undergoing Coronary Artery Bypass Grafting (CABG) Compared to Percutaneous Coronary Intervention (PCI)—Insights From Two Large Multi-centre Australian Registries

Heart, Lung and Circulation, 2008