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Background: Private healthcare providers are important to tuberculosis (TB) management globally, although internationally there are reports of suboptimal management and disparities in treatment commencement in the private sector. We compared the management of TB patients receiving private versus public healthcare in Victoria, an industrialised setting with low tuberculosis (TB) incidence., Methods: Retrospective cohort study: 2002-2015. Private healthcare provision was included as an independent variable in several multivariate logistic and Cox proportional hazard regression models that assessed a range of outcome variables, encompassing treatment commencement delays, management and treatment outcomes., Results: Of 5106 patients, 275 (5.4%) exclusively saw private providers, and 4714 (92.32%) public. Private care was associated with a shorter delay to presentation (HR 1.36, p = 0.065, 95% CI 1.02-2.00). Private patients were less likely to have genotypic testing (OR 0.66, p = 0.009, 95% CI 0.48-0.90), those with pulmonary involvement were less likely to have a sputum smear (OR 0.52, p = 0.011, 95% CI 0.31-0.86) and provided samples were less likely to be positive (OR 0.54, p = 0.070, 95% CI 0.27-1.05). Private patients with extrapulmonary TB were less likely to have a smear sample (OR 0.7, 95% CI 0.48-0.90, p = 0.009) and radiological abnormalities (OR 0.71, p = 0.070, 95% CI 0.27-1.05). Treatment commencement delays from presentation were comparable for cases with pulmonary involvement and extrapulmonary TB, although public extrapulmonary TB patients received radiological examinations slightly earlier than private patients (HR 0.79, p = 0.043, 95% CI 0.63-0.99) and public patients with pulmonary involvement from high burden settings commenced treatment following an abnormal CXR more promptly than their private counterparts (HR 0.41, p = 0.011, 95% CI 0.21-0.81). Private patients were more likely to receive <4 first-line medications (OR 2.17, p = 0.001, 95% CI 1.36-3.46), but treatment outcomes were comparable between sectors., Conclusions: The differences we identified are likely to reflect differing case-mix as well as clinician practice. Sputum smear status was an important covariable in our analysis; with its addition we found no significant disparity in the health-system delay to treatment commencement between sectors. Our study highlights the importance of TB programs engaging with private providers, enabling comprehensive data collection that is necessary for thorough and true comparison of TB management and optimisation of care.

Setting: Victoria, Australia, is an industrialised setting with low tuberculosis (TB) incidence and universal health care. Individually tailored adherence support for self-administered daily anti-tuberculosis treatment is provided. Directly observed treatment (DOT) is very rarely used., Objective: To review the rate of recurrent TB in Victoria between 2002 and 2014., Design: This was a retrospective cohort study. All recurrent episodes of TB were reviewed and 24-locus MIRU-VNTR (mycobacterial interspersed repetitive units-variable number of tandem repeats) molecular typing was used where possible to determine the likelihood of relapse or reinfection., Results: Of 4766 notifications, 32 (0.7%) were recurrent episodes. Of 20 episodes that occurred in patients who had previously completed treatment, 11 were culture-positive (0.4% of 3012 culture-positive episodes): 9 were likely relapses (distinguishable at no more than one of 24 loci) and two were likely reinfections, giving a TB relapse rate among culture-positive episodes of 52.5/100 000 person-years (mean time to study end per patient of 5.7 years). The median time until relapse was 18 months (interquartile range 12-30)., Conclusions: The low rate of relapse in our setting demonstrates that individually tailored adherence support for self-administered anti-tuberculosis treatment can achieve excellent treatment outcomes.

Heterotopic implantation of transcatheter tricuspid valve is a new treatment option for tricuspid regurgitation. Transcatheter tricuspid valves are implanted onto the cavoatrial junction in order to avoid the challenging task of anchoring the valve onto the complex tricuspid valve annulus. However, little is known about optimum extent of oversizing of the valved stent in a vena cava. In this study, we implanted valves of the same diameter onto the larger sized inferior vena cava (IVC) and a smaller sized superior vena cava (SVC). The valve in the IVC was oversized by 10.7% while the valve in the SVC was oversized by 21.6%. Finite element analysis was performed (i) to assess the strain on the nitinol stent during manufacturing and deployment; (ii) the stents were deployed in a patient-specific vena cava model and the intramural stress of the vena cava was calculated computationally. These valves were fabricated and placed in a silicone model of a patient-specific right atrium which was part of a mock circulatory system that emulated the patho-physiological flow rate and pressure of a patient with tricuspid regurgitation. Flow measurements were conducted by particle image velocimetry (PIV). It was found that the maximum crimping strain on the nitinol stent was 6.85% which was lower than the critical threshold of 10%. The maximum stress on the vena cava was located at the spot where the hooks met the wall. The maximum stress on the IVC was 0.5098 MPa while the maximum stress on the SVC was 0.7 MPa. The maximum Reynolds shear stress (mRSS) in the vena cava was found to be higher in the IVC than SVC with the highest mRSS being 1741 dynes/cm(2) found in the region of high flow during the peak flow phase. The overtly oversized valve in the SVC did not cause flow disturbances and exhibited mostly laminar flows. The mRSS at the downstream of the vena cava valve and the middle of the atrium remained at low magnitudes. However, velocity fluctuations were high in the IVC in all the time points measured. In conclusion, oversizing the valve may assist anchorage; yet, careful consideration should be taken in choosing the extent of oversizing as it may lead to adverse effects.

Myxomatous mitral valve prolapse (MMVP) and fibroelastic deficiency (FED) are two common variants of degenerative mitral valve disease (DMVD), which is a leading cause of mitral regurgitation worldwide. While pathohistological studies have revealed differences in extracellular matrix content in MMVP and FED, the molecular mechanisms underlying these two disease entities remain to be elucidated. By using surgically removed valvular specimens from MMVP and FED patients that were categorized on the basis of echocardiographic, clinical and operative findings, a cluster of microRNAs that expressed differentially were identified. The expressions of has-miR-500, -3174, -17, -1193, -646, -1273e, -4298, -203, -505, and -939 showed significant differences between MMVP and FED after applying Bonferroni correction (p < 0.002174). The possible involvement of microRNAs in the pathogenesis of DMVD were further suggested by the presences of in silico predicted target sites on a number of genes reported to be involved in extracellular matrix homeostasis and marker genes for cellular composition of mitral valves, including decorin (DCN), aggrecan (ACAN), fibromodulin (FMOD), α actin 2 (ACTA2), extracellular matrix protein 2 (ECM2), desmin (DES), endothelial cell specific molecule 1 (ESM1), and platelet/ endothelial cell adhesion molecule 1 (PECAM1), as well as inverse correlations of selected microRNA and mRNA expression in MMVP and FED groups. Our results provide evidence that distinct molecular mechanisms underlie MMVP and FED. Moreover, the microRNAs identified may be targets for the future development of diagnostic biomarkers and therapeutics.

Background: There are limited studies describing the epidemiology of childhood brain injury, especially in developing countries. This study analyses data from the Malaysian National Trauma Database (NTrD) registry to estimate the incidence of childhood brain injury among various demographic groups within the state of Selangor and Federal Territory of Kuala Lumpur., Methods: This study analysed all traumatic brain injury cases for children ages 0-19 included in the 2010 NTrD report., Results: A total of 5,836 paediatric patients were admitted to emergency departments (ED) of reporting hospitals for trauma. Of these, 742 patients (12.7 %) suffered from brain injuries. Among those with brain injuries, the mortality rate was 11.9 and 71.2 % were aged between 15 and 19. Traffic accidents were the most common mode of injury (95.4 %). Out of the total for traffic accidents, 80.2 % of brain injuries were incurred in motorcycle accidents. Severity of injury was higher among males and patients who were transferred or referred to the reporting centres from other clinics. Glasgow Coma Scale (GCS) total score and type of admission were found to be statistically significant, χ (2) (5, N = 178) = 66.53, p < 0.001, in predicting patient outcomes. According to this analysis, the overall rate of childhood brain injury for this one year period was 32 per 100,000 children while the incidence of significant (moderate to severe) brain injury was approximately 8 per 100,000 children., Conclusions: This study provides an overview of traumatic brain injury rates among children within the most populous region of Malaysia. Most brain injuries occurred among older male children, with traffic, specifically motorcycle-related, accidents being the main mode of injury. These findings point to risk factors that could be targeted for future injury prevention programs.

Objective: We compared intracranial collaterals on pretreatment and day 2 brain CT angiograms (CTA) to assess their evolution and relationship with functional outcomes in acute ischemic stroke (AIS) patients treated with IV tissue plasminogen activator (tPA)., Methods: Consecutive AIS patients who underwent pretreatment and day 2 CTA and received IV tPA during 2010-2013 were included. Collaterals were evaluated by 2 independent neuroradiologists using 3 predefined criteria: the Miteff system, the Maas system, and 20-point collateral scale by the Alberta Stroke Program Early CT Score methodology. We stratified our cohort by baseline pre-tPA state of their collaterals and by recanalization status of the primary vessel for analysis. Good outcomes at 3 months were defined by a modified Rankin Scale score of 0-1., Results: This study included 209 patients. Delayed collateral recruitment by any grading system was not associated with good outcomes. All 3 scoring systems showed that collateral recruitment on the follow-up CTA from a baseline poor collateral state was significantly associated with poor outcome and increased bleeding risk. When the primary vessel remained persistently occluded, collateral recruitment was significantly associated with worse outcomes. Interestingly, collateral recruitment was significantly associated with increased mortality in 2 of the 3 grading systems., Conclusions: Not all collateral recruitment is beneficial; delayed collateral recruitment may be different from early recruitment and can result in worse outcomes and higher mortality. Prethrombolysis collateral status and recanalization are determinants of how intracranial collateral evolution affects functional outcomes., (© 2016 American Academy of Neurology.)

Background: It is often stated that the lifetime risk of developing active TB after an index infection is 5% to 10%, one-half of which accrues in the 2 to 5 years following infection. The goal of this study was to determine whether such estimates are consistent with local programmatic data., Methods: This study included close contacts of individuals with active pulmonary TB notified in the Australian state of Victoria from January 1, 2005, to December 31, 2013, who we deemed to have been infected as a result of their exposure. Survival analysis was first performed on the assumption of complete follow-up through to the end of the study period. The analysis was then repeated with imputation of censorship for migration, death, and preventive treatment, using local mortality and migration data combined with programmatic data on the administration of preventive therapy., Results: Of 613 infected close contacts, 67 (10.9%) developed active TB during the study period. Assuming complete follow-up, the 1,650-day cumulative hazard was 11.5% (95% CI, 8.9-14.1). With imputation of censorship for death, migration, and preventive therapy, the median 1,650-day cumulative hazard over 10,000 simulations was 14.5% (95% CI, 11.1-17.9). Most risk accrued in the first 5 months after infection, and risk was greatest in the group aged < 5 years, reaching 56.0% with imputation, but it was also elevated in older children (27.6% in the group aged 5-14 years)., Conclusions: The risk of active TB following infection is several-fold higher than traditionally accepted estimates, and it is particularly high immediately following infection and in children., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the burden of and trends in paediatric tuberculosis (TB) in Australia between 2003 and 2012., Design: A retrospective analysis of TB data from the National Notifiable Diseases Surveillance System (NNDSS) on TB in children (under 15 years of age) during the 10-year period, 2003-2012., Results: TB notifications in Australia during the study period included 538 children (range, 37-66 cases per year), representing 4.6% of the total TB case load during the period (range, 3.8%-5.8% each year). Place of birth was recorded for 524 patients (97.4%); of these, 230 (43.9%) were born in Australia, 294 (56.1%) overseas. The average annual notification rate was 1.31 (95% CI, 1.20-1.43) cases per 100 000 child population. The rate was higher for overseas-born than for Australian-born children (9.57 [95% CI, 8.51-10.73] v 0.61 [95% CI, 0.53-0.69] cases per 100 000 children. The overall rate was highest among those aged 0-4 years. The annual notification rate was three times higher for Indigenous children than for non-Indigenous Australian-born children. Of 427 patients (79.4% of total) for whom the method of case detection was recorded, 37.0% were detected by contact screening, 8.7% by post-arrival immigration screening, and 54.3% by passive case detection. Pulmonary TB was the most common diagnostic classification (64.7% of patients). The most common risk factors were close contact with a TB case and recent residence in a country with a high incidence of TB. Treatment outcomes were satisfactory; 89.4% of children had completed treatment or were cured., Conclusions: The burden of paediatric TB in Australia is low but has not changed over the past decade. The highest rates are among children born overseas, emphasising the important role of immigration screening as Australia aspires to eliminate TB.

Aim: To review the programmatic use of the tuberculin skin test (TST) following tuberculosis (TB) exposure in Victoria, Australia., Methods: A retrospective review of data collected for public health surveillance was performed to identify contact demographic factors, including bacille Calmette-Guérin (BCG) status and age and outcomes of TST., Results: Contact tracing was performed for 15 094 people, of whom 13 427 (89.0%) had a TST performed. The TST was positive in 31.4% (95%CI 30.6-32.2) of all contacts, and 48.8% of contacts born outside of Australia. Amongst contacts who were TST-negative at baseline, the conversion rate following exposure was 14.8%. Conversion was most common in those aged 45-54 years, with <12% positivity in both the youngest (<5 years) and oldest (⩾65 years) age groups. Active TB developed in 1.1% of all contacts. Contacts aged <5 years had the highest risk of developing active TB following exposure (3.8%), while low risk was seen in those aged ⩾65 years (0.3%)., Conclusion: Overall, contact tracing and TST in this setting appear to yield a high proportion of people at risk for the development of active TB. The yield of testing in some groups, particularly those aged ⩾65 years, was low, and investigation of alternative strategies should be considered.

Introduction: Tuberculin skin testing (TST) has been the accepted Australian standard for investigating contacts following exposure to infectious tuberculosis (TB). In recent years, the availability of the interferon-gamma release assays (IGRA) has introduced a potential alternative test but data on its use in this context are limited., Methods: A prospective longitudinal cohort study was conducted from 2008-2013 to review the use of IGRA and subsequent TB disease following testing in a state-wide contact tracing program. Additional information on the experience and acceptability of IGRA in this context was also obtained through program staff surveys following implementation., Results: IGRA testing was performed on 643 contacts, with a mean follow-up of 3.7 years. IGRA was primarily used to supplement TST, most commonly due to borderline TST reactivity in individuals who had bacille Calmette-Guérin vaccination. Where both TST and IGRA were performed, correlation of test results was poor (kappa=0.35). The negative predictive value for later development of active TB was 99.5%., Conclusions: Our experience suggests that IGRA are able to be incorporated safely and effectively as a supplement to TST-based contact tracing., (This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the Online, Services and External Relations Branch, Department of Health, GPO Box 9848, Canberra ACT 2601, or by email to copyright@health.gov.au.)

Aim: To determine angle closure agreements between gonioscopy and anterior segment optical coherence tomography (AS-OCT), as well as gonioscopy and spectral domain OCT (SD-OCT). A secondary objective was to quantify inter-observer agreements of AS-OCT and SD-OCT assessments., Methods: Seventeen consecutive subjects (33 eyes) were recruited from the study hospital's Glaucoma clinic. Gonioscopy was performed by a glaucomatologist masked to OCT results. OCT images were read independently by 2 other glaucomatologists masked to gonioscopy findings as well as each other's analyses of OCT images., Results: Totally 84.8% and 45.5% of scleral spurs were visualized in AS-OCT and SD-OCT images respectively (P<0.01). The agreement for angle closure between AS-OCT and gonioscopy was fair at k=0.31 (95% confidence interval, CI: 0.03-0.59) and k=0.35 (95% CI: 0.07-0.63) for reader 1 and 2 respectively. The agreement for angle closure between SD-OCT and gonioscopy was fair at k=0.21 (95% CI: 0.07-0.49) and slight at k=0.17 (95% CI: 0.08-0.42) for reader 1 and 2 respectively. The inter-reader agreement for angle closure in AS-OCT images was moderate at 0.51 (95% CI: 0.13-0.88). The inter-reader agreement for angle closure in SD-OCT images was slight at 0.18 (95% CI: 0.08-0.45)., Conclusion: Significant proportion of scleral spurs were not visualised with SD-OCT imaging resulting in weaker inter-reader agreements. Identifying other angle landmarks in SD-OCT images will allow more consistent angle closure assessments. Gonioscopy and OCT imaging do not always agree in angle closure assessments but have their own advantages, and should be used together and not exclusively.

Percutaneous mitral valve repair with the MitraClip® (Abbott, Abbott Park, IL) can reduce mitral regurgitation (MR) and improve symptoms and quality of life in patients with severe mitral regurgitation. While this therapy is safe, there have been reports of single leaflet detachment where the MitraClip remains attached only to one leaflet of the mitral valve after deployment. Most of these cases occur within the first month of the procedure but there have been reports of late detachment occurring after this period. This case report describes a patient with severe functional MR who underwent an initial successful MitraClip procedure with implantation of two clips but subsequently developed late detachment of one clip. It also discusses the challenges and feasibility of performing a repeat MitraClip procedure in these patients., (© 2013 Wiley Periodicals, Inc.)

Purpose: Ischemia/reperfusion injury remains an untreated clinical problem in patients with acute myocardial infarction (AMI) despite significant advances in emergent revascularization through percutaneous coronary intervention (PCI). Pharmacological intervention for infarct size reduction is unavailable. We have identified that the medications milrinone and esmolol, when administered together at the beginning of the reperfusion, significantly decrease infarct size via reducing reperfusion injury in an experimental model. The present study tested the safety of combination therapy of milrinone and esmolol (M + E) in patients with AMI., Methods: Sixteen subjects with AMI requiring PCI were consecutively recruited. M + E was intravenously infused simultaneously for 10 min started at 5 min before anticipated angioplasty balloon inflation. Another 16 consecutively recruited AMI patients requiring PCI served as a placebo arm treated per routine clinical protocol. Blood pressure (BP) and heart rate (HR) were monitored continuously during PCI., Results: M + E combination therapy resulted in a trend of non-significant reduction in BP compared with a control group. There was a modest but significant increase in HR at the later phase of M + E infusion compared with a control group. No significant cardiac arrhythmia was induced during M + E infusion., Conclusions: The combination therapy with M + E produces a minimal change in hemodynamics and appears safe as an adjunctive therapy to PCI in AMI patients. Further studies are warranted.

Anomalous origin of the right coronary artery (ARCA) and focal nodular hyperplasia (FNH) are frequently reported in association with congenital heart abnormalities but not with each other. We propose that both conditions may share common origins in a maladative hyperplastic response to differential vascular flow due to developmental arterial malformations or aberrant Notch signalling during simultaneous gut and cardiac vasculorigenesis.

Background & Objective: During the temperate out-of-season months in Australia in late 2010 and early 2011, an unprecedented high number of influenza notifications were recorded. We aimed to assess the significance of these notifications., Methods: For Australia, we used laboratory-confirmed cases notified to the WHO FluNet surveillance tool; the percentage of these that were positive; notifications by state and influenza type and subtype; and surveillance data from Google FluTrends. For the state of Victoria, we used laboratory-confirmed notified cases and influenza-like illness (ILI) proportions. We compared virus characterisation using haemagglutination-inhibition assays and phylogenetic analysis of the haemagglutinin gene for seasonal and out-of-season notifications., Results: The increase in notifications was most marked in tropical and subtropical Australia, but the number of out-of-season notifications in temperate Victoria was more than five times higher than the average of the previous three seasons. However, ILI proportions in spring-summer were not different to previous years. All out-of-season viruses tested were antigenically and genetically similar to those tested during either the 2010 or 2011 influenza seasons. An increase in the number of laboratories testing for influenza has led to an increase in the number of tests performed and cases notified., Conclusion: An increase in influenza infections in spring-summer of 2010-11 in tropical and temperate Australia was not associated with any differences in virus characterisation compared with viruses that circulated in the preceding and following winters. This increase probably reflected a natural variation in out-of-season virus circulation, which was amplified by increased laboratory testing., (© 2012 John Wiley & Sons Ltd.)

Introduction: Health authorities find thresholds useful to gauge the start and severity of influenza seasons. We explored a method for deriving thresholds proposed in an influenza surveillance manual published by the World Health Organization (WHO)., Methods: For 2002-2011, we analysed two routine influenza-like-illness (ILI) datasets, general practice sentinel surveillance and a locum medical service sentinel surveillance, plus laboratory data and hospital admissions for influenza. For each sentinel dataset, we created two composite variables from the product of weekly ILI data and the relevant laboratory data, indicating the proportion of tested specimens that were positive. For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. From the thresholds, we compared the seasonal onset, end and intensity across all datasets from 2002-2011. Correlation between datasets was assessed using the mean correlation coefficient., Results: The median week of peak activity was week 34 for all datasets, except hospital data (week 35). Means and medians were comparable and the 90% upper CIs were similar to the 95(th) percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. The composite variables improved the agreements between the ILI and other datasets. Datasets were well correlated, with mean correlation coefficients of >0.75 for a range of combinations., Conclusions: Thresholds for influenza surveillance are easily derived from historical surveillance and laboratory data using the approach proposed by WHO. Use of composite variables is helpful for describing influenza season characteristics.

Vaccine effectiveness (VE) studies are often made for a "season" which may refer to different analysis periods in different systems. We examined whether the use of four different definitions of season would materially affect estimates of influenza VE using data from the Victorian general practice sentinel surveillance network for 2007-2012. In general, the choice of analysis period had little effect on VE estimates (≤ five percentage points) when there was a statistically significant protective effect of vaccination (2007, 2010 and 2012). In contrast, for years when the analysis period varied widely depending on the method used and when VE estimates were imprecise, the change in VE estimate was as much as 43 percentage points (2008). Studies of influenza VE should clearly define the analysis period used and, where possible, provide sensitivity analyses to align this definition with other VE studies., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: transcatheter aortic valve implantation is now an accepted therapy for patients with severe aortic valve stenosis who are deemed inoperable, and it is a reasonable alternative for patients with high surgical risk. This study assessed the clinical outcomes of this procedure and the implications of transcatheter aortic valve implantation for such patients., Methods: 14 consecutive patients with severe aortic valve stenosis, who underwent transcatheter aortic valve implantation, were assessed. Baseline clinical characteristics, procedural information, and clinical outcomes and complications were compared at baseline and at follow-up. Thirty-day mortality was also assessed., Results: the mean age of the patients was 81 ± 8 years (35% females). The mean Society of Thoracic Surgeons score was 6.8 ± 3.7. Most patients had chronic kidney disease with an estimated glomerular filtration rate of 44.5 ± 14.9 mL·kg(-1)·min(-1). The mean annulus diameter was 21.9 ± 1.7 mm, and 8 (57%) patients received 23-mm valves. After transcatheter aortic valve implantation, the mean transaortic gradient and aortic valve area improved from 42.9 ± 19.4 to 8.9 ± 3.1 mm Hg (p < 0.001) and 0.7 ± 0.1 to 1.5 ± 0.3 cm(2) (p < 0.001), respectively. The 30-day mortality for this cohort was 7%., Conclusion: transcatheter aortic valve implantation can be performed successfully in carefully selected Asian patients. The decision to undertake this procedure should be guided by the surgical team.

Background: Systemic right ventricular systolic dysfunction is common late after atrial switch surgery for transposition of the great arteries. Total isovolumic time is the time that the ventricle is neither ejecting nor filling and is calculated without relying on geometric assumptions. We assessed resting total isovolumic time in this population and its relationship to exercise capacity., Methods: A total of 40 adult patients with transposition of the great arteries after atrial switch - and 10 healthy controls - underwent transthoracic echocardiography and cardiopulmonary exercise testing from January, 2006 to January, 2009. Resting total isovolumic time was measured in seconds per minute: 60 minus total ejection time plus total filling time., Results: The mean age was 31.6 plus or minus 7.6 years, and 38.0% were men. There were 16 patients (40%) who had more than or equal to moderate systolic dysfunction of the right ventricle. Intra- and inter-observer agreement was good for total isovolumic time, which was significantly prolonged in patients compared with controls (12.0 plus or minus 3.9 seconds per minute versus 6.0 plus or minus 1.8 seconds per minute, p-value less than 0.001) and correlated significantly with peak oxygen consumption (r equals minus 0.63, p-value less than 0.001). The correlation strengthened (r equals minus 0.73, p-value less than 0.001) after excluding seven patients with exercise-induced cyanosis. No relationship was found between exercise capacity and right ventricular ejection fraction or long-axis amplitude., Conclusion: Resting isovolumic time is prolonged after atrial switch for patients with transposition of the great arteries. It is highly reproducible and relates well to exercise capacity.

Background: Atrial tachyarrhythmias are a known complication late after Fontan operation. Limited information is available on their prognostic value., Methods: All patients with previous Fontan operation followed at our institution since 1999 were identified from the electronic database and included in this study. Demographic and clinical characteristics including history of atrial tachyarrhythmias were recorded at the earliest full clinical assessment and patients were followed thereafter for all-cause mortality and hospitalization., Results: A total of 98 patients, mean age 31.5 ± 8.9 years, 43.8% male, 31.6% with a total cavopulmonary connection (TCPC) were identified. A history of atrial tachyarrhythmia was present at baseline in 60.2% of patients who were older (33.0 ± 8.3 vs 29.1 ± 9.4 years, p=0.002), less likely to have a TCPC (13.5% vs 58.9%, p<0.001), and more symptomatic in terms of NYHA class (51.9% vs 26.7%, p=0.007) compared to arrhythmia-free patients. During a median follow-up of 6.7 years 18 patients died and 64 patients were hospitalized. Even after adjustment for baseline clinical characteristics, atrial tachyarrhythmia was an independent predictor of death (propensity score adjusted HR 9.35, 95% CI: 1.10-79.18, p=0.04, c-statistic 0.88) and composite of death or hospitalization (propensity score adjusted HR 5.00, 95% CI: 2.47-10.09, p<0.0001)., Conclusions: In adult patients with a Fontan-type operation, the presence of atrial tachyarrhythmias is associated with higher morbidity and mortality at mid-term follow-up. Whether early arrhythmia targeting intervention may improve clinical outcome needs to be studied in a prospective manner., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Electrocardiogram (ECG) is a useful but imperfect investigation in the diagnosis and possible follow-up of structural heart disease such as ventricular hypertrophy. Different ECG criteria with different sensitivity and specificity are available to aid the detection of left or right ventricular hypertrophy. Subsequent echocardiography can help in the quantification of ventricular mass and identification of the aetiology.

Objectives: This study assesses if there exists a high-risk period for cerebrovascular events (CeV) after transcatheter aortic valve implantation (TAVI)., Background: Even though acute strokes after TAVI have been described, it is uncertain if stroke rates continue to remain high in the early months after TAVI. Furthermore, the optimal dose and duration of thromboprophylaxis is unclear., Methods: Patients who underwent TAVI were evaluated at baseline, at discharge, at 1 and 6 months, and yearly. Risk factors for CeV events, procedural details, and antithrombotic therapy were recorded. Outcomes assessed were CeV events and death. The timing of such events, predictors, and impact on survival were analyzed., Results: A total of 253 patients were assessed. Median age was 85 years. The median Society of Thoracic Surgeons score was 8.1% (interquartile range [IQR]: 5.5% to 12.0%). Risk factors included smoking (47%), hypertension (70%), dyslipidemia (66%), and diabetes mellitus (25%). Twenty-three percent had known cerebrovascular disease and 39% had atrial fibrillation. Median follow-up was 455 days (IQR: 160 to 912 days) at which time 23 patients experienced a CeV event. The incidence was highest in the first 24 h but remained high for 2 months. In-hospital mortality rate after a CeV event was 21%. A prior history of CeV disease was an independent predictor of an event (hazard ratio: 4.23, 95% CI: 1.60 to 11.11, p = 0.004)., Conclusions: The incidence of CeV events is highest within 24 h of TAVI, but this risk may remain elevated for up to 2 months. A prior history of cerebrovascular disease is an independent predictor. This may have implications for patient selection and antithrombotic strategies., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) is a rapidly evolving strategy for therapy of aortic stenosis. We describe the effect of the learning curve from the first 270 high-risk patients in Vancouver, Canada., Methods: Patients underwent TAVI by transfemoral (63%) or transapical (37%) routes using balloon expandable valves. The experience was divided into the first half (FH, patients 1-135) and second half (SH, patients 136-270)., Results: The mean age was 83.2 ± 8 years (FH 83 ± 12 vs. SH 81 ± 7 years, P = 0.12). The mean Society of Thoracic Surgeons Score (STS) was 9.5% ± 5.2%- FH 10.5 vs. SH 8.5% (P = 0.01). The overall procedural success rate in the FH was 92.6%, improving to 97.8% in the SH (P = 0.05). The transfemoral procedural success improved-FH 89.3% to SH 98.8% (P = 0.01). The transapical procedural success remained high-FH 98.0% to SH 96.1% (P = 0.53). The overall 30-day mortality was 9.6%, improving from FH 13.3% to SH 5.9% (P = 0.04). In the transfemoral cases, 30-day mortality decreased by 56% [10.7-4.7%, P = 0.14], and similarly in transapical cases [17.6-7.8%, P = 0.14]. In-hospital stroke occurred in 3.3% (FH 3.7% vs. SH 2.9%, P = 0.74). The overall need for a new permanent pacemaker was 5.9% (FH 5.9% vs. SH 5.9%, P = 1). The overall major vascular injury rate was 6.7% (FH 8.1% vs. SH 5.2%, P = 0.33). The overall incidence of coronary vessel occlusion was 1.1% (FH 1.5 % vs. SH 0.7%, P = 0.56). Device embolization or failure to cross the valve was rare and largely seen in the FH only. Procedural experience (>135 procedures) was an independent predictor of 30-day survival (HR: 6.7, 95% CI: 1.2-18.1, P = 0.03)., Conclusion: TAVI outcomes improve with experience and device development. While overall complication rates are low, scope remains to further reduce procedural adverse events., (Copyright © 2011 Wiley Periodicals, Inc.)

Introduction: Iron deficiency is common in cyanotic congenital heart disease (CHD) and results in reduced exercise tolerance. Currently, iron replacement is advocated with limited evidence in cyanotic CHD. We investigated the safety and efficacy of iron replacement therapy in this population., Methods: Twenty-five iron-deficient cyanotic CHD patients were prospectively studied between August 2008 and January 2009. Oral ferrous fumarate was titrated to a maximum dose of 200mg thrice-daily. The CAMPHOR QoL questionnaire, 6 minute walk test (6MWT) and cardiopulmonary exercise testing were conducted at baseline and after 3 months of treatment., Results: Mean age was 39.9 ± 10.9 years, 80% females. Fourteen had Eisenmenger syndrome, 6 complex cyanotic disease and 5 Fontan circulation. There were no adverse effects necessitating termination of treatment. After 3 months of treatment, hemoglobin (19.0 ± 2.9 g/dL to 20.4 ± 2.7 g/dL, p<0.001), ferritin (13.3 ± 4.7 μg/L to 54.1 ± 24.2 μg/L, p<0.001) and transferrin saturation (17.8 ± 9.6% to 34.8 ± 23.4%, p<0.001) significantly increased. Significant improvements were also detected in the total CAMPHOR score (20.7 ± 10.9 to 16.2 ± 10.4, p=0.001) and 6MWT distance (371.7 ± 84.7 m to 402.8.0±74.9m, p=0.001). Peak VO(2) remained unchanged (40.7 ± 9.2% to 43.8 ± 12.4% of predicted, p=0.15)., Conclusion: Three months of iron replacement therapy in iron-deficient cyanotic CHD patients was safe and resulted in significant improvement in exercise tolerance and quality of life. Identification of iron deficiency and appropriate replacement should be advocated in these patients., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with Eisenmenger syndrome (ES) have a decreased exercise capacity and poor quality of life (QoL). While patients may survive to middle adulthood, the burden of disease is disabling. Sildenafil seems to improve exercise tolerance and hemodynamics, but there is no data to date on its impact on QoL., Methods: Eisenmenger patients in New York Heart Association (NYHA) class III were recruited in a prospective study of efficacy and safety of oral sildenafil. The QoL endpoint was assessed using a disease-specific questionnaire (CAMPHOR). Exercise capacity was assessed by means of six minute walk test (6MWT). All patients underwent comprehensive assessment at baseline and after 3months of treatment., Results: Twelve patients (mean age was 34.3±10.2, 83% female) with various cardiac anatomies were recruited. No major adverse events during the follow-up or significant drop in resting oxygen saturation were recorded. After 3months of oral sildenafil therapy, all patients improved to NYHA II with a concomitant improvement in 6MWT distance (347.3±80.7 to 392.5±82.0m, p=0.002). All components of the CAMPHOR score, relating to symptoms, activity and QoL, improved significantly resulting in substantial improvement in the total CAMPHOR score (27.6±10.5 to 15.8±10.4, p=0.002)., Conclusions: Three months of sildenafil therapy in adults with ES was well tolerated and associated with significant improvement in the QoL CAMPHOR questionnaire and in NYHA class and exercise capacity. Larger studies are warranted to assess long term efficacy of oral sildenafil and potential impact on survival., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with congenitally corrected transposition of the great arteries (ccTGA) have significantly reduced exercise tolerance. Progressive right ventricular (RV) dysfunction with tricuspid regurgitation (TR) and other haemodynamic lesions are common among them. We hypothesised that interaction of these factors may result in increased systemic RV filling pressure, which in turn impact on exercise capacity., Methods: Patients with ccTGA in functional class I or II, able to perform treadmill exercise and without resting cyanosis were enrolled. All patients underwent cardiopulmonary exercise testing and transthoracic echocardiographic examination. RV filling pressure was estimated using tissue Doppler imaging (TDI) techniques by measuring early annular diastolic velocity (Ea) and the ratio of the transtricuspid inflow to the early annular diastolic velocity (E/Ea)., Results: A total of 27 patients (mean age 41 years, 48% female) were assessed, the majority (63%) asymptomatic. Many patients had coexistent haemodynamic lesions including shunts, pulmonary stenosis, TR and systemic ventricular dysfunction. Average percentage predicted peak oxygen consumption, VE/VCO(2) slope and heart rate reserve were abnormal in this population. Patients with moderately/severely impaired exercise capacity (≤ 60% predicted peak VO(2)) had significantly higher E/Ea ratios compared to those with normal/mildly impaired exercise capacity (septal E/Ea = 17.1 ± 9.7 vs 8.8 ± 1.6 and lateral E/Ea = 11.5 ± 5.8 vs 6.6 ± 1.3, p = 0.007 and 0.01 respectively)., Conclusion: Reduced exercise capacity is common in adults with ccTGA even among asymptomatic patients and relates to increased RV filling pressures assessed by TDI. This index could potentially be used to optimize therapy or prognosticate adverse events in ccTGA patients., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study aims to assess the mid- to long-term follow-up of patients after valve embolization at the time of transcatheter aortic valve implantation (TAVI)., Background: Transcatheter heart valve (THV) embolization is a rare but serious complication during TAVI. Although various techniques have been developed to manage acute complications and reduce periprocedural morbidity/mortality, long-term clinical and hemodynamic consequences after these events are unknown., Methods: Patients who developed THV embolization after TAVI were prospectively assessed. Clinical and echocardiographic characteristics were recorded at baseline and after successful TAVI/surgical aortic valve replacement. The THV migration and strut fractures/degeneration were assessed by computed tomography., Results: A total of 7 patients had THV embolization, all of which occurred immediately after valve deployment. The embolized THV was repositioned in the aortic arch proximal to the left subclavian artery (n = 2), immediately distal to the left subclavian artery (n = 2), and in the abdominal aorta (n = 3). A second THV was implanted successfully at the same sitting in 4 patients and at the time of a second procedure in 2 patients. Elective conventional aortic valve replacement was performed in 1 patient. Median follow-up was 1,085 days. One patient died during follow-up from an unrelated cause. The remaining 6 survivors were in New York Heart Association functional class I or II at final follow-up. Mid-term computed tomography follow-up (n = 4,591 to 1,548 days) showed that the leaflets of the embolized THV remain open in all phases of the cardiac cycle. There was also no strut fracture or migration of these valves., Conclusions: Clinical outcomes remain good when THV embolization is managed effectively. There are no apparent hemodynamic consequences of a second valve placed in the series. These embolized valves remain in a stable position with no evidence of strut fractures at mid-term follow-up., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to describe a method of paravalvular leak closure using a purpose-specific occlusion device., Background: Transcatheter closure of paravalvular leaks has been hampered by technical challenges, the limitations of available imaging modalities, and the lack of closure devices specifically designed for this purpose., Methods: Patients with severe symptomatic paravalvular regurgitation at high risk for repeat surgery underwent transcatheter leak closure. Both left ventricular puncture and retrograde transfemoral approaches were used with fluoroscopic and 3-dimensional transesophageal guidance. A purpose-specific occluder (Vascular Plug III, AGA Medical Corp., Plymouth, Minnesota) was used., Results: Five patients with severe prosthetic mitral and aortic paravalvular leaks underwent attempted closure. Implantation of the device was successfully accomplished in all. In 1 patient, the plug interfered with closure of a mechanical valve leaflet and was removed and replaced with an alternate device. Complications included pericardial bleeding in 2 patients with a transapical approach. There was no procedural mortality. At a median follow-up of 191 days (interquartile range [IQR] 169 to 203 days) all patients were alive. New York Heart Association functional class fell from 4 (IQR 3 to 4) to 2 (IQR 2 to 3), hemoglobin rose from 89 g/l (IQR 87 to 108 g/l) to 115 g/l (IQR 104 to 118 g/l), creatinine fell from 109 micromol/l (IQR 106 to 132 micromol/l) to 89 micromol/l (IQR 89 to 126 micromol/l). Median echocardiographic follow-up at 58 days (IQR 56 to 70 days) reported residual regurgitation to be reduced from grade 4 to grade 2 (IQR 1.5 to 2.25)., Conclusions: Closure of mitral and aortic prosthetic paravalvular leaks with the Vascular Plug III using either a transapical (mitral) or a retrograde (aortic) approach appears promising., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Antiplatelet agents, beta-blockers, statins and ACE inhibitors have been shown to reduce mortality in patients following myocardial infarction (MI). However, it is uncertain if the combination of these agents has a similar impact on mortality following MI in patients with renal dysfunction., Methods: We studied 5529 consecutive patients with confirmed MI between January 2000 and December 2003. Data on baseline demographics, co-morbidities and in-hospital management were collected prospectively. Glomerular filtration rate (GFR) was estimated using the 4-component Modification of Diet in Renal Disease equation. Based on discharge use of evidence-based medications, the patients were divided into those using 0, 1, 2, 3 or 4 medications. The impact of medication use on 1-year mortality was then assessed for patients with GFR > or =60 ml/min/1.73 m2 (group I) and GFR < 60 ml/min/1.73 m2 (group 2)., Results: Mean age was 63 +/- 13 years with 71% men.The prevalence of reduced GFR was 35% and the adjusted odds ratio for I-year mortality of patients in group 2 compared to those in group I was 1.86 (95% CI 1.54-2.25, P < 0.001). Compared with patients with no medication, the adjusted odds ratio for 1-year mortality was lower in patients with 1, 2, 3 and 4 medications in both groups. There was no significant interaction between the number of medications used and GFR., Conclusion: Increased use of combined evidence-based medications was independently associated with a lower 1-year post MI mortality. Such therapies offer similar survival benefit in patients with and without renal dysfunction.

Neurohormonal activation is prevalent in adults with congenital heart disease, but its relation to outcome remains unknown. B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were measured prospectively in 49 patients with adult congenital heart disease, who were followed up for a median of 7.9 years (interquartile range 7.7 to 8.2). Cox proportional hazards regression analysis was used to determine the relation of BNP and ANP concentrations to all-cause mortality. The mean age at baseline was 33.9 +/- 11.3 years, and 46.9% of patients were men. Most patients (77.5%) were symptomatic (20.4% had New York Heart Association class III), 10 (20.4%) were cyanotic, and 28 (57.1%) had systemic ventricular dysfunction (moderate or severe in 18.4%). The median concentration of BNP was 52.7 pg/ml (interquartile range 39.1 to 115.4) and of ANP was 47.4 pg/ml (interquartile range 19.7 to 112.8). Of the 49 patients, 11 (22.4%) died during the follow-up period. Both BNP and ANP were strong predictors of mortality (hazard ratio per 100-pg/ml increase 1.80, 95% confidence interval 1.38 to 2.34, p <0.0001; and hazard ratio per 100-pg/ml increase 1.21, 95% confidence interval 1.12 to 1.32, p <0.0001, respectively). A BNP value >78 pg/ml predicted death with a sensitivity of 100% and specificity of 76.3% (area under the curve 0.91, p = 0.0001). An ANP value of >146 pg/ml predicted death with a sensitivity of 72.7% and specificity 94.7% (area under the curve 0.89, p = 0.0001). No patients with a BNP level <78 pg/ml died during the follow-up period. In conclusion, the BNP and ANP levels strongly predicted death in symptomatic ambulatory patients with adult congenital heart disease during mid-term follow-up and could be used as a simple clinical marker for risk stratification in this population., (Copyright 2010 Elsevier Inc. All rights reserved.)

Aims: We studied the prevalence of hyponatraemia and its prognostic implications in a large population of adult patients with congenital heart disease (ACHD)., Methods and Results: A total of 1004 ACHD patients were retrospectively entered in this study (mean age 36.2 +/- 14.4 years, 48.7% male). Cox regression was used to estimate mortality associated with hyponatraemia, adjusted for potential confounders using both multivariable regression and propensity score matching. Mean sodium concentration in this ACHD cohort was 137.6 +/- 2.6 mmol/L. The overall prevalence of hyponatraemia in this cohort was 15.5% and was highest in congenitally corrected transposition (33.3%), after Fontan operation (29.6%), and in patients with Eisenmenger syndrome (22.0%). Predictors of hyponatraemia were worse functional class, cyanosis, higher serum creatinine levels, and treatment with diuretics. Patients were followed for a median of 4.1 years, during which there were 96 deaths. Hyponatraemia was a strong predictor of death, independent of age, previous surgery, functional class, systemic ventricular function, creatinine levels, and the use of diuretics (adjusted HR 2.82, 95% CI: 1.72-4.63, P < 0.0001)., Conclusion: Hyponatraemia is relatively common in ACHD. Hyponatraemia carries a three-fold higher risk of death in ACHD and is a simple, cheap but powerful marker of mortality.

Background: Primary percutaneous coronary intervention is the standard reperfusion strategy for ST-segment elevation myocardial infarction in our center. We aimed to shorten the median door-to-balloon time from over 100 minutes to 90 minutes or less., Methods: We have been using three strategies since March 2007 to shorten the door-to-balloon time: (1) the intervention team is now activated by emergency department physicians (where previously it had been activated by coronary care unit); (2) all members of the intervention team have converted from using pagers to using cell phones; and (3) as soon as the intervention team is activated, patients are transferred immediately to the cardiac catheterization laboratory (where previously they had waited in the emergency department for the intervention team to arrive). An in-house physician and a nurse would stay with the patients before arrival of the intervention team., Results: During 12 months, 285 nontransfer patients (analyzed, n = 270) underwent primary PCI. The shortest monthly median door-to-balloon time was 59 minutes; the longest monthly median door-to-balloon time was 111 minutes. The overall median door-to-balloon time for the entire 12 months was 72 minutes. On a per-month basis, the median door-to-balloon time was 90 minutes or less in 10 of 12 months. On a per-patient basis, the median door-to-balloon time was 90 minutes or less in 182 patients (67.4%). There was 1 case (0.4%) of inappropriate activation by the emergency department. While waiting for the intervention team to convene, 1 patient (0.4%) deteriorated and had to be resuscitated in the cardiac catheterization laboratory., Conclusions: Improved health care delivery can be achieved by changing simple and inexpensive operational processes.

Objective: We present our clinical experience of StarClose in patients undergoing coronary interventions, including its use in patients after repeated puncture of the same femoral access site., Background: The StarClose is a novel vascular closure device that deploys a small, flexible, circumferential nitinol clip onto the femoral artery surface., Methods: In this study, 103 consecutive patients (24% with repeated punctures) who underwent percutaneous coronary intervention and received a StarClose were followed up prospectively. The patients were assessed for vascular complications prior to hospital discharge. Device success, based on time-to-hemostasis, was divided into (1) immediate success: hemostasis achieved immediately after StarClose deployment without the need for adjunctive manual compression, (2) partial success: occurrence of minor oozing after StarClose deployment and hemostasis achieved after <3 minutes of manual compression, and (3) device failure: need for adjunctive manual compression for >3 minutes., Results: Immediate success, partial success, and device failure rates were 74% (n = 68), 16% (n = 15), and 10% (n = 9), respectively. There were no major complications attributable to the StarClose device. There were 10 (9.7%) cases of minor complications; all were recurrent wound bleeding requiring manual compression in the wards. Among these 10 cases of recurrent bleeding, 5 (50%) had initial device success (immediate success, n = 2, partial success, n = 3) in the catheterization laboratory. The risk for recurrent bleeding was 2.9% after immediate device success and 20.0% after partial device success., Conclusion: Our study found no major complications but a 10% failure rate and a 9.7% rate of minor complications. Close surveillance is important as there is a risk for recurrent bleeding, especially in patients with partial device success as defined in this report.

Antiplatelet drugs, beta-blockers, statins, and angiotensinogen-converting enzyme inhibitors reduce mortality following myocardial infarction (MI). The data on the impact of combination evidence-based medications on mortality following acute MI in elderly patients are limited. In this study, 5529 patients with MI admitted between January 2000 and December 2003 were assessed. Based on discharge use of evidence-based medications, the patients were divided into those using 0, 1, 2, 3, or 4 medications. The impact of medications on 1-year mortality was assessed for patients younger than 75 years and 75 years and older. Mean age of the patients was 63+/-13 years (71% male). The unadjusted 1-year mortality post-MI was 18.3% and 52.7% for young and elderly patients, respectively. Compared with patients with 0 medications, the adjusted odds ratio for 1-year mortality was lower in patients with 1, 2, 3, and 4 medications in both groups. Use of combination evidence-based medications was independently associated with lower 1-year post-MI mortality irrespective of age.