Coronary computed tomography angiography and its increasing application in day to day cardiology practice.

Coronary artery disease (CAD) is the leading single cause of death in Australia affecting around 1.4 million people. Coronary computed tomography angiography has an established role in the assessment of patients with low to intermediate pretest probability for CAD who have chest pain and is typically used with the aim to rule out significant coronary artery stenosis. Use was initially limited because of concerns over radiation exposure, a Medicare rebate restricted to specialist referrals and an absence of data supporting its use as an alternative to functional testing in patients with chest pain. Recent advances in scanner technology and image sequencing, along with data from randomised control trials, have addressed these issues and indicate that coronary computed tomography angiography will play a greater role in the assessment of CAD in the coming years.

Outcomes of transcatheter aortic valve implantation in high surgical risk and inoperable patients with aortic stenosis: a single Australian Centre experience.

BACKGROUND: Degenerative aortic stenosis is the most common valvular heart disease in the elderly, and many patients are not suitable for aortic valve replacement surgery. Transcatheter aortic valve implantation (TAVI) is a new therapeutic option for selected patients at high risk for surgery. AIM: To evaluate the safety and efficacy of TAVI in Australian patients. METHODS: This is a prospective study of patients undergoing TAVI for severe symptomatic aortic stenosis at The Prince Charles Hospital, Brisbane, Australia between August 2008 and July 2013. Patients were at high risk of surgical aortic valve replacement, or inoperable, as deemed by a multidisciplinary 'heart team'. Outcomes include procedural success and complications, 30-day and 1-year mortality and stroke, combined end-points as outlined by the Valve Academic Research Consortium 2 consensus document. RESULTS: Two hundred and nine patients underwent TAVI during the study period. The mean age was 83.7 ± 6.7 years, and 101 (48%) were men. The valve systems utilised were as follows: Edwards-SAPIEN valve in 104 (49.5%), Medtronic CoreValve in 86 (41.2%) and Boston Scientific Lotus valve in 19 (9.3%) patients. Thirty-day and 1-year mortality rates were 5.7% and 11.5% respectively. Thirty-day and 1-year stroke rates were 4.3% and 6.2% respectively. The composite end-points of device success, early safety and clinical efficacy occurred in 80.4%, 27.3% and 68.4%. CONCLUSIONS: TAVI with various valve systems, delivered through several approaches, is feasible in high surgical risk and inoperable patients with severe aortic stenosis, with acceptable outcomes at short-term and intermediate-term follow up.

Takotsubo cardiomyopathy: an Australian single centre experience with medium term follow up.

BACKGROUND: Takotsubo cardiomyopathy (TC) is increasingly recognised in patients presenting with features of acute coronary syndrome. We present a single centre experience of TC with medium term follow up. METHODS: Fifty-two consecutive patients presenting with a diagnosis of TC were included. The clinical presentation, complications, baseline and follow-up echocardiograms and cardiac magnetic resonance imaging were analysed. RESULTS: Fifty-one patients were female. A stressful event preceded presentation in 37 (71%) patients. Chest pain was the most common symptom (83%). Two patients presented with an out-of-hospital cardiac arrest. ST segment elevation (40%) and global T wave inversion (44%) were the most frequent electrocardiogram changes. Left ventricular assessment demonstrated typical apical ballooning in 41 patients and 11 patients demonstrated the mid-wall variant. In-hospital complications occurred in 11 patients (21%) and included acute pulmonary oedema (n = 2), cardiogenic shock (n = 5); two of whom had a significant left ventricular outflow gradient, atrial fibrillation (n = 1), left ventricular thrombus (n = 2) and a cerebrovascular event (n = 2). Left ventricular function at presentation and follow up was compared in 40 patients. The mean ejection fraction in this group at presentation was 47% (20-70%) compared with that at follow up of 63% (44-76%). There were no significant complications or recurrences at follow up. CONCLUSIONS: While TC is a reversible condition with low rates of complications and recurrence at follow up it is, as demonstrated in our cohort, associated with significant in-hospital morbidity in a proportion of patients.

Percutaneous ASD closure in a large Australian series: short- and long-term outcomes.

AIM: To assess the clinical and echocardiographic outcomes in patients referred for device closure of atrial septal defects in a tertiary referral hospital in Australia. METHODS: A prospective follow-up study was performed on all patients who had device closure of a secundum atrial septal defect (ASD) from June 1999 to December 2007. Clinical and echocardiographic data at the time of implantation and follow-up is presented. RESULTS: 176 patients were referred for shunt closure of ASD. All patients had a significant shunt defined as a shunt with right heart dilatation and/or a shunt ratio of at least 1.5:1. The majority were female (67%) and the average age was 36.5 ± 22.7 years; age range 3-84. The average hospital admission time was 2.5 ± 1.7 days. The average follow-up occurred at 3.7 ± 3.6 months for the first follow-up and 26.3 ± 18.2 months (range 3 months-7.8 years) for the long-term follow-up. Baseline echocardiogram findings showed the majority had a normal left ventricular ejection fraction (99%); average LVEF=63.2 ± 7.2% while the right ventricle was dilated in 61% of patients. Procedure information: The average procedure time was 94.8 ± 36.4 min. Procedural imaging was performed using Transoesophageal echocardiography (TOE) in 107 cases (61%); Intracardiac Echocardiography (ICE) in 69 (39%). Device use was as follows: Amplatzer=156 cases, Helex=18, and Starflex=2. Postprocedure shunt assessment by transthoracic echocardiography showed successful closure (no shunt or trivial shunt) in 99% cases. Two patients were referred for inpatient surgery due to a significant residual shunt in one case and an unstable device in another. One patient who had an unstable device had their device repositioned successfully. Atrial arrhythmia was the most common complication occurring in the peri-implantation period in 12 cases (6%) with four further cases at final up. The high prevalence of right ventricular dilatation in 65% patients at baseline had improved significantly at the first and long term follow-up to 2% (p=0.0001). CONCLUSION: Device closure of secundum atrial septal defects in this large Australian cohort demonstrates a high procedural success rate with a low incidence of complications in the short and long term.

High-dose tirofiban with enoxaparin and inflammatory markers in high-risk percutaneous intervention.

AIM: The study assessed the benefit of high bolus dose tirofiban (HD-tirofiban) with enoxaparin compared with HD-tirofiban with unfractionated heparin (UFH). The study examined markers of platelet activation, thrombin generation and inflammation. MATERIALS AND METHODS: The study is a prospective single centre open-label trial of patients with high-risk acute coronary syndrome treated with percutaneous intervention (PCI) who were randomized to anticoagulation with UFH or enoxaparin with HD-tirofiban (25 microg kg(-1) bolus). This study measured a panel of platelet activation markers, inflammatory biomarkers and thrombus generation between the two groups. RESULT: Sixty patients undergoing high-risk PCI were enroled in the study. Platelet inhibition as assessed by whole blood aggregometry following HD-tirofiban infusion was similar in both the UFH and enoxaparin groups. CD40 ligand expression on platelets was significantly reduced following PCI with HD-tirofiban and either UFH or enoxaparin. Following PCI, there were significant reductions measured in other markers of platelet activation including PAC-1, P selectin, factor V/Va, platelet-monocyte aggregates and monocyte expression of Mac-1 as determined by analysis of venous blood samples using flow cytometry. Prothrombin fragment 1+2, D-dimer, von Willebrand factor and high sensitive C-reactive protein levels were significantly less post PCI in the enoxaparin group compared with those patients receiving UFH. CONCLUSION: The combination of HD tirofiban with enoxaparin resulted in an attenuated inflammatory response when compared with that of the combination of HD tirofiban with UFH.

Improvement after angioplasty and stenting of pulmonary arteries due to sarcoid mediastinal fibrosis.

We describe a series of cases referred to our institution with working diagnoses of chronic thrombo-embolic pulmonary hypertension (CTEPH) for consideration of surgical pulmonary thrombo-endarterectomy (PTE). Investigations in two cases revealed extrinsic compression of the pulmonary arteries from massive mediastinal lymphadenopathy (mediastinal fibrosis) due to underlying sarcoidosis. Angioplasty and stenting of the pulmonary arteries were performed in all cases with sustained haemodynamic and functional improvement. This highlights the value of new imaging modalities in delineating causes of pulmonary hypertension, and demonstrates an interventional approach for selected cases.

Treatment options and strategies for acute severe pulmonary embolism.

Pulmonary thromboembolism (PE) is the third most frequent cause of cardiovascular death after ischaemic heart disease and stroke. In fatal PE, 2/3 of patients die within first hour of presentation. There is a clinical impetus to rapidly recognize, risk-stratify and appropriately treat patients with acute severe PE. Current recommendations present conflicting classification systems, and there is often some confusion in the clinical evaluation and management of patients with acute severe PE. This review presents a series of real clinical cases, which illustrate the available treatment options, ranging from conservative therapy to thrombolysis through to percutaneous catheter fragmentation and open surgical embolectomy. We evaluate the evidence for the various strategies and propose an algorithm for clinicians with a focus on early risk stratification and timely referral. This is particularly relevant to regional and remote centres, as well as secondary and tertiary institutions.

Platelet-monocyte aggregates predict troponin rise after percutaneous coronary intervention and are inhibited by Abciximab.

BACKGROUND: Platelet-monocyte aggregates and other markers of platelet activation were investigated before and after percutaneous coronary intervention (PCI) with abciximab therapy. The study sought to assess the relationship between the level of platelet-monocyte aggregation and increases in cardiac troponin I post coronary intervention. METHODS: Blood samples were collected from 40 patients before PCI and 10 min after abciximab administration. These were tested for platelet activation markers by flow cytometry. Cardiac troponin I levels were assayed at baseline and at 24 h post PCI. RESULTS: Compared to healthy controls, patients with coronary artery disease had elevated markers of platelet activation including platelet-monocyte aggregates, P-selectin and PAC-1 (a marker specific for activated glycoprotein IIb/IIIa) prior to PCI. Increased levels of platelet-monocyte aggregates before PCI were associated with increased expression of P-selectin on the platelet surface. Abciximab therapy reduced platelet-monocyte aggregate levels but had no effect on P-selectin expression. The high levels of expression of activated glycoprotein IIb/IIIa (PAC-1) on platelets prior to PCI was reduced with abciximab therapy. Patients with higher levels of platelet-monocyte aggregates prior to PCI were more likely to develop an elevation of cardiac troponin I during the 24 h after PCI. CONCLUSIONS: Increased levels of platelet-monocyte aggregates may predict patients at risk for troponin elevation following PCI and identify those most likely to benefit from abciximab.

Next generation TAVI with the Lotus Valve System: a repositionable and fully retrievable transcatheter aortic valve prosthesis.

Transcatheter aortic valve implantation (TAVI) is the new standard of care for selected patients with severe symptomatic aortic stenosis who are at high risk for surgical aortic valve replacement (AVR), or are inoperable. Multicentre randomised controlled trials have demonstrated equivalent or superior clinical outcomes for TAVI compared to AVR in carefully selected patient cohorts. A number of important limitations were observed with early generation TAVI valves and their delivery systems, and rapid evolution of the technology continues. The Lotus Valve System aims to address a number of these limitations - it is repositionable and retrievable, and has an adaptive seal to prevent paravalvular aortic regurgitation. Early clinical outcomes for the Lotus Valve System have recently been published with promising results in terms of paravalvular regurgitation and repositionability.

Analysis of various nucleosides in plasma using solid phase extraction and high-performance liquid chromatography with UV detection.

The National Cancer Institute (NCI) has screened many nucleosides for antiviral activity to the HIV-1 virus. Drugs demonstrating antiviral activity are tested in animal models to evaluate their toxicity and pharmacokinetic characteristics. These drugs are subsequently evaluated for efficacy in human clinical trials. Sensitive analytical methodology is needed to quantify nucleosides in plasma and other biological matrices in support of these studies. Battelle has modified and validated a reversed phase high-performance liquid chromatography (HPLC) method for several of these nucleosides that could be easily adapted for similar compounds. Methods have been validated for 6-chloro-2',3'-dideoxyguanosine (6ClddG), 6-chloro-2',3'-dideoxyinosine (6ClddI) and their primary metabolites 2',3'-dideoxyguanosine (ddG) and 2',3'-dideoxyinosine (ddI) in both rat and dog plasma containing EDTA. The method has also been validated for 2'-fluoro-2',3'-dideoxyara-adenosine (betaFlddA) and its primary metabolite 2'-beta-fluorodideoxyinosine (betaFddI) in rat plasma containing heparin. Calibration plasma standards were prepared over ranges of 0.1-10 microg ml(-1) for betaFlddA and betaFddI, 0.1-50 microg ml(-1) for 6ClddG and ddG, and 0.25-50 microg ml(-1) for 6ClddI and ddI in plasma containing 4 microg ml(-1) pentostatin. The addition of pentostatin to the plasma samples inhibits in-vitro deamination of the drug after collection. Quality control (QC) standards were prepared containing the appropriate anticoagulant and 4 microg ml(-1) pentostatin at concentrations within each of the bracketed calibration ranges in plasma. These methods have been successfully applied to plasma samples generated during various animal studies.

Influence of exogenous steroids, nutrition and calf removal on reproductive performance of anestrous beef cows.

Methods for inducing a fertile estrus in anestrous beef cows suckling calves were explored in three studies. Trial 1 . Eighty-two primiparous and pluriparous Brahman-Hereford crossbred and Angus cows suckling calves were divided into four groups: 1) good body condition, high level of nutrition (GH); 2) good body condition, low level of nutrition (GL); 3) poor body condition, high level of nutrition (PH); 4) poor body condition, low level of nutrition (PL). All cows received the Shang Treatment (S). Following treatment, more cows (P<0.05) ovulated in the GH group (95%) than either the GL (61%), PH (58%), or PL (53%) group. Pregnancy rates were low and were not different between groups following the insemination taking place 54 hours after implant removal or after cows had been bred for 21 days. Trial 2 . One hundred fourteen two-year-old Santa Gertrudis-Hereford crossbred cows in poor body condition were divided into four groups. Forty-nine cows received S treatment and 65 cows served as controls (C) with approximately half of each group fed a high (H) or a medium (M) level of nutrition (SH, SM, CH, CM). One cow in the SH group ovulated and was pregnant 21 days after breeding. The remaining cows failed to exhibit estrus, ovulate or become pregnant. Trial 3 . Cows used in this trial were those from Trial 2 which did not exhibit estrus nor had a palpable corpus luteum present 21 days after implant removal. Cows were divided into 1) control (C), 2) wean (W), 3) wean + Syncro-Mate-B (W+SMB) and 4) Syncro-Mate-B + wean (SMB+W). The percentage of cows ovulating by 2 and 40 days after the start of breeding was similar (P>0.05) in the W, W+SMB, and SMB+W groups but all were greater (P<0.05) than the percentage of cows ovulating in the C groups. Pregnancy rates of cows in the W+SMB and SMB+W groups were higher (P<0.05) than pregnancy rates of cows in the W and C groups by two days after the start of breeding. Pregnancy rates 40 days after the start of breeding were higher (P<0.05) for cows in the W, W+SMB) and SMB+W groups than for cows in the C group.

Initial experience with the balloon expandable Edwards-SAPIEN Transcatheter Heart Valve in Australia and New Zealand: the SOURCE ANZ registry: outcomes at 30 days and one year.

BACKGROUND: We report the findings of the SOURCE-ANZ registry of the clinical outcomes of the Edwards SAPIEN™ Transcatheter Heart Valve (THV) in the Australian and New Zealand (ANZ) clinical environment. METHODS: This single arm registry of select patients treated in eight centres, represent the initial experience within ANZ with the balloon expandable Edwards SAPIEN THV delivered by transfemoral (TF) and transapical (TA) access. RESULTS: The total enrolment for the study was 132 patients, 63 patients treated by TF, 56 by TA, and 2 patients were withdrawn from the study. The mean ages: 83.7 (TF) and 81.7 (TA), female: 34.3% (TF) and 61.3% (TA), logistic EuroSCORE: 26.8% (TF) and 28.8% (TA), and with procedural success (successful implant without conversion to surgery or death): 92.4% (TF) and 87.1% (TA) (p=0.32). Outcomes were not significantly different between TF and TA implants. These included one year mortality of 13.6% (TF) and 21.7% (TA) (p=0.24), MACCE: 16.7% (TF) and 28.3% (TA) (p=0.12), pacemaker: 4.6% (TF) and 8.3% (TA) (p=0.39), and VARC major vascular complication of 4.6% (TF) and 5.0% (TA) (p=0.91). CONCLUSION: TAVI in the ANZ clinical environment has demonstrated excellent outcomes for both the TA and TF approaches in highly selected patients. These results are consistent with those demonstrated in European, Canadian registries and the pivotal US clinical trials. ACTRN12611001026910.

Pre-hospital fibrinolysis in the management of patients with ST elevation acute coronary syndrome: review of the evidence, implementation and future directions.

Time to reperfusion is among the strongest predictors of clinical outcome in patients who present with ST elevation acute myocardial infarction. When time to access is equivalent, primary percutaneous coronary intervention has demonstrated superior outcomes to fibrinolysis. However, where significant delays exist in accessing percutaneous intervention, fibrinolysis has an important role. The potential for fibrinolysis delivery in the pre-hospital setting means that delays to primary percutaneous intervention need to be considered from the time that the patient becomes eligible for fibrinolysis in the field. This can be particularly challenging in patients with symptom duration ofless than two hours, as some evidence suggests fibrinolysis may be particularly beneficial in this early phase. Additionally, access to primary percutaneous intervention provided by an experienced operator, in a timely manner at any time of the day or night, is not an available option in many healthcare settings. This review focuses on the current evidence and practice of pre-hospital fibrinolysis and assesses potential roles for this therapy in the future.

Anti-Platelet Therapy for Acute Coronary Syndrome: A Review of Currently Available Agents and What the Future Holds.

Dual anti-platelet therapy remains a cornerstone in the management of patients suffering from acute coronary syndromes (ACS). The combination of aspirin and clopidogrel has been shown to result in significant reductions in cardiovascular end points including recurrent infarction and death in several randomised control trial of patients with ACS. However, many patients still experience ischaemic events on the combination of aspirin and clopidogrel. Aspirin is a relatively weak anti platelet agent. Clopidogrel is a pro drug that required activation by hepatic metabolism and hence its onset of action is delayed; there is genetic variation in the clinical response to the drug, the platelet inhibition is irreversible and no intravenous form is available. Consequently new anti-platelet agents have been developed to address the short falls of this combination therapy. This paper discusses existing anti-platelet regimes and focuses on novel antiplatelet agents that are currently under clinical evaluation.

Trends in intra-aortic balloon counterpulsation: comparison of a 669 record Australian dataset with the multinational Benchmark Counterpulsation Outcomes Registry.

The aim of this study was to review and describe indications for intraaortic balloon counterpulsation (IABP) use and identify the impact these have on outcomes at an Australian cardiothoracic tertiary referral hospital. A secondary aim was comparison of the Australian practice with a large multinational IABP data registry. Patient demographics, IABP indication, IABP complication rate and mortality in 662 patients treated with IABP at The Prince Charles Hospital (TPCH), Brisbane, between January 1994 and December 2004 inclusive were compared with The Benchmark Counterpulsation Outcomes Registry. Data were collected between 1994 and 2000 by retrospective patient record review and prospectively using the Benchmark database from 2001 to 2004. Statistical analysis was undertaken using SAS (v8.2) software. The mean age of patients managed with IABP at TPCH (71.6% male) was 63.4 years (SD 12.4). In-hospital mortality rate was 22% and the complication rate was 10.3%. TPCH indications for IABP were: weaning from cardiopulmonary bypass (34.2%); cardiogenic shock (24.4%); preoperative support (13%); catheter laboratory support (10.6%); refractory ventricular failure (7.3%); ischaemia related to intractable ventricular arrhythmias (4.5%); unstable refractory angina (4%); mechanical complications due to acute myocardial infarction (1.2%) and other (0.4%) (0.4% not reported). In comparison to Benchmark, IABP at TPCH demonstrated a prejudice toward intraoperative use (34.2% versus 16.6%; P < or = 0.0001) and an aversion to catheter laboratory support (10.6% versus 19%; P < or = 0.0001). TPCH and Benchmark IABP outcomes demonstrated comparable mortality (22% versus 20.8%; P = ns) but increased TPCH complications (10.3% vs. 6.2%; P < or = 0.0001) owing to a 2% difference in observed insertion site bleeding.

Measurements of optical turbulence with higher-order structure functions.

Higher-order structure functions have been used to extract atmospheric optical C(n)(2) profiles from a vertical sequence of temperature data collected by a single probe carried by a meteorological balloon. This technique circumvents trends and fluctuations in the atmospheric mean temperature and simplifies the equipment and complexity of measurement collection compared with traditional, horizontal differential-probe pair systems.