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Background: Mediated by outcomes such as improved exercise capacity, cardiac rehabilitation (CR) reduces morbidity and mortality. For accuracy, an individual CR patient's change must be measured reliably, an issue not typically considered in practice. Drawing from psychometric theory, we calculated reliable change indices (RCIs), to measure individual CR patients’ true clinical change, apart from that from error and test practice/exposure, in exercise capacity, anxiety, and depression. Methods: Indirectly calculated exercise capacity (peak metabolic equivalents [METs]) and psychological symptoms were each measured twice, 1 week apart, by administering treadmill tests or the Hospital Anxiety and Depression Scale (HADS) to separate samples of 35 (mean age: 59.0 years; 6 women) and 96 (mean age: 64.4 years; 32 women) CR patients, respectively. Using test-retest reliability and mean difference scores from these samples to estimate error and practice/exposure effects, we calculated RCIs for a separate cohort (n = 2066; mean age: 62.0 years; 533 women) who completed 6-month CR, and compared change distributions (worsened/unchanged/improved) based on critical RCIs, mean and percent changes, cut-off scores, and standard deviations. Results: Practice/exposure effects were nonsignificant, except the mean HADS anxiety score decreased significantly (P ≤ 0.013; d = 0.17, small effect). Test-retest reliabilities were high (METs r = 0.934; HADS anxiety score r = 0.912; HADS depression score r = 0.90; P < 0.001). Among 2066 CR patients, RCI distributions differed (P < 0.001) from those of most other change criteria. Conclusions: Change ascertainment depends on criterion choice. A Canadian Cardiovascular Society CR quality indicator of increase by 0.5 MET may be too small to assess individuals’ functional capacity change. RCIs offer a pragmatic approach to benchmarking reliable change frequency, and pending further validation, could be used for feedback to individual patients. Résumé: Contexte: Grâce à des résultats tels que l'amélioration de la capacité d'exercice, la réadaptation cardiaque (RC) réduit la morbidité et la mortalité. Pour être précis, le changement de RC d'un patient doit être mesuré de manière fiable, un aspect qui n'est généralement pas pris en compte dans la pratique. En nous inspirant de la théorie psychométrique, nous avons déterminé des indices de changement fiables afin de mesurer le véritable changement clinique individuel des patients en RC en lien avec la capacité d'entraînement, l'anxiété et la dépression et indépendamment des erreurs et de la pratique du test/l'exposition au test. Méthodologie: La capacité d'entraînement calculée indirectement (l’équivalent métabolique maximum [MET]) et les symptômes psychologiques ont été mesurés deux fois, à une semaine d'intervalle, par le biais de tests sur tapis roulant ou de l’échelle de l’évaluation de l'anxiété et de la dépression en milieu hospitalier (HADS), auxquels ont respectivement été soumis des échantillons de 35 personnes en RC (âge moyen : 59,0 ans; 6 femmes) et de 96 personnes en RC (âge moyen : 64,4 ans; 32 femmes). En recourant à la fiabilité test-retest et aux écarts moyens dans les scores de ces échantillons pour faire une approximation des effets d'erreur et de pratique/exposition, nous avons déterminé des indices de changement fiables pour une cohorte distincte (n = 2 066; âge moyen : 62,0 ans; 533 femmes) qui a terminé une RC de six mois, et comparé la répartition des changements (aggravé/inchangé/amélioré) sur la base des indices de changement fiables critiques, des changements moyens et en pourcentage, des scores-seuils et des écarts types. Résultats: Les effets de la pratique/exposition étaient peu significatifs, sauf une diminution du score moyen de l'anxiété sur l’échelle HADS (p ≤ 0,013; d = 0,17, petit effet). La fiabilité test-retest était élevée (MET, r = 0,934; score de l'anxiété sur l’échelle HADS, r = 0,912; score de la dépression sur l’échelle HADS, r = 0,90; p < 0,001). Parmi les 2 066 patients en RC, la répartition des indices de changement fiables différait (p < 0,001) de celle de la plupart des autres critères de changement. Conclusions: Le constat du changement dépend du choix du critère. Une augmentation de 0,5 MET selon l'indicateur de qualité en RC de la Société canadienne de cardiologie est peut-être trop faible pour évaluer le changement de capacité fonctionnelle des individus. Les indices de changement fiables offrent une approche pragmatique pour comparer la fréquence du changement fiable et, en attendant une vérification plus poussée, ils pourraient être utilisés comme rétroaction fournie individuellement aux patients.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a group of cardiomyopathies associated with ventricular arrhythmias predominantly arising from the right ventricle, sudden cardiac death and right ventricular failure, caused largely due to inherited mutations in proteins of the desmosomal complex. Whilst long recognised as a cause of sudden cardiac death (SCD) during exercise, it has recently been recognised that intense and prolonged exercise can worsen the disease resulting in earlier and more severe phenotypic expression. Changes in cardiac structure and function as a result of exercise training also pose challenges with diagnosis as enlargement of the right ventricle is commonly seen in endurance athletes. Advice regarding restriction of exercise is an important part of patient management, not only of those with established disease, but also in individuals known to carry gene mutations associated with development of ARVC.

Despite well-established efficacy for patients with a cardiovascular diagnosis or event, exercise-based cardiac rehabilitation program participation and completion has remained alarmingly low due to both system-level barriers and patient-level factors. Patient mental health, particularly depression, is now recognized as significantly associated with reduced enrollment, participation, attendance, and completion of a cardiac rehabilitation program. More recently, anxiety sensitivity has emerged as an independent construct, related to but distinct from both depression and anxiety. Anxiety sensitivity has been reported to be adversely associated with participation in exercise and, thus, may be important for patients in cardiac rehabilitation. Accordingly, the objective of this study was to conduct a scoping review to summarize the evidence for associations between anxiety sensitivity and cardiovascular disease risk factors, exercise, and clinical outcomes in cardiac rehabilitation.A formal scoping review, following PRISMA-ScR guidelines, was undertaken. Searches of MEDLINE, Web of Science, CINAHL, PSYCINFO, and Scopus databases were conducted, supplemented by hand searches; studies published through December of 2020 were included. The initial screening was based on titles and abstracts and the second stage of screening was based on full text examination.The final search results included 28 studies. Studies reported statistically significant associations between anxiety sensitivity and exercise, cardiovascular disease, and participation in cardiac rehabilitation. Many studies, however, were conducted in non-clinical, community-based populations; there were few studies conducted in cardiovascular disease and cardiac rehabilitation clinical patient populations. Additionally, significant gaps remain in our understanding of the sex-based differences in the complex relationships between anxiety sensitivity, exercise and cardiac rehabilitation.More research is needed to understand specific associations between anxiety sensitivity and clinical outcomes among clinical cardiovascular disease patients and participants in cardiac rehabilitation programs. Treatment of anxiety sensitivity to optimize clinical outcomes in cardiac rehabilitation programs should be investigated in future studies.

Background Historical data suggesting poor survival in patients with aortic stenosis (AS) who do not undergo treatment are largely confined to patients with severe AS. Objectives This study sought to determine the prognostic impact of all levels of native valvular AS. Methods Severity of AS was characterized by convention and by statistical distribution in 122,809 male patients (mean age 61 ± 17 years) and 118,494 female patients (mean age 62 ± 19 years), with measured aortic valve (AV) mean gradient, peak velocity, and/or area. The relationship between AS severity and survival was then examined during median 1,208 days (interquartile range: 598 to 2,177 days) of follow-up. Patients with previous aortic valve intervention were excluded. Results Overall, 16,129 (6.7%), 3,315 (1.4%), and 6,383 (2.6%) patients had mild, moderate, and severe AS, respectively. On an adjusted basis (vs. no AS; 5-year mortality 19%), patients with mild to severe AS had an increasing risk of long-term mortality (adjusted hazard ratio: 1.44 to 2.09; p 50%) and cardiovascular disease was evident from a mean AV gradient >20.0 mm Hg (moderate AS) after adjusting for age, sex, left ventricular systolic or diastolic dysfunction, and aortic regurgitation. Conclusions These data confirm that when left untreated, severe AS is associated with poor long-term survival. Moreover, they also suggest poor survival rates in patients with moderate AS. (National Echocardiographic Database of Australia [NEDA]; ACTRN12617001387314)

There is increasing evidence that current thresholds for diagnosing pulmonary hypertension (PHT) underestimate the prognostic impact of PHT.The aim of this study was to determine the prognostic impact of increasing pulmonary pressures within the National Echocardiography Database of Australia cohort (n = 313,492).The distribution of estimated right ventricular systolic pressure (eRVSP) was examined in 157,842 men and women. All had data linkage to long-term survival during median follow-up of 4.2 years (interquartile range: 2.2 to 7.5 years).The cohort comprised 74,405 men and 83,437 women 65.6 ± 17.7 years of age. Overall, 17,955 (11.4%), 7,016 (4.4%), and 4,515 (2.9%) subjects had eRVSP levels indicative of mild (40 to 49 mm Hg), moderate (50 to 59 mm Hg), or severe (≥60 mm Hg) PHT, respectively, assuming a right atrial pressure of 5 mm Hg. These subjects were more likely to die during long-term follow up (for severe PHT, adjusted hazard ratio: 9.73; 95% confidence interval: 8.60 to 11.0; p 0.001). After adjustment for age, sex, and evidence of left heart disease, those subjects with eRVSP levels within the third (28.05 to 32.0 mm Hg; hazard ratio: 1.410; 95% confidence interval: 1.310 to 1.517) and fourth (32.05 to 38.83 mm Hg; hazard ratio: 1.979; 95% confidence interval: 1.853 to 2.114) quintiles had significantly higher mortality (p 0.001) than those in the lowest quintile. Accordingly, a clear and consistent threshold of increased mortality (including 1- and 5-year actuarial mortality) around an eRVSP of 30.0 mm Hg was evident.In this large and unique cohort, the prognostic impact of clinically accepted levels of PHT was confirmed. Moreover, a distinctly lower threshold for increased risk for mortality (eRVSP30.0 mm Hg) indicative of PHT was identified. (A Longitudinal Cohort Study of Echocardiograms From Public and Private Echocardiography Laboratories From Around Australia, Linked With the National Deaths Index; ACTRN12617001387314).

Background: Clinically evident primary heart involvement due to systemic sclerosis (SHI) is considered a poor prognostic factor and is a leading cause of systemic sclerosis (SSc) related death. Yet, there remains no consensus definition of SHI and poor understanding of the natural history and risk factors for the development of SHI. Methods: We performed a scoping literature review of published articles with a primary focus of SHI to capture previously used definitions of SHI and items used to measure SHI. Any factors reported to be associated with an increased risk of SHI were recorded. Results: Of the 2436 records identified in a search of MEDLINE, EMBASE and PubMed databases, 295 were included in the final scoping review. Analysis of the literature revealed studies of variable quality, generally low patient numbers and highly heterogeneous definitions of SHI within studies. There is no clear consensus from the literature as to the scope of SHI and the prognostic significance of sub-clinical investigation abnormalities commonly detected. Conclusion: The lack of a standardised definition of SHI remains a significant unmet need in SSc. The results of this review will assist in the development of consensus classification criteria to enable more accurate quantification of the burden of SHI, identification of factors associated with increased risk of developing SHI, and evaluation of the efficacy of any novel therapeutic strategies.

The National Echocardiography Database Australia (NEDA) is a new echocardiography database collecting digital measurements on both a retrospective and prospective basis. To date, echocardiographic data from 435,133 individuals (aged 61.6 ± 17.9 years) with linkage to 59,725 all-cause deaths during a median of 40 months follow-up have been collected. These data will inform a number of initial analyses focusing on pulmonary hypertension, aortic stenosis and the role of artificial intelligence to facilitate accurate diagnoses of cardiac abnormalities.

Graphical abstract, Highlights • DSS is generally an acquired and progressive condition. • Subaortic stenosis often takes the form of a discrete crescentic fibromuscular ridge in the LVOT. • DSS should be considered when an elevated aortic Doppler gradient is seen in the presence of normal aortic leaflet mobility. • Surgery is considered when the peak instantaneous gradient is >50 to 60 mm Hg. • DSS has a high rate of recurrence following surgical intervention.

Background Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity and associated metabolic complications. Obesity and type 2 diabetes are associated with increased oxidative stress. Previous studies have examined changes in plasma oxidative stress after laparoscopic Roux-en-Y gastric bypass, but there is limited evidence of the effects of LSG. Objectives To examine the effects of LSG on plasma thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAOS) at 1 and 6 months after LSG in patients with obesity and impaired glucose regulation. Setting University hospital, United Kingdom. Methods Twenty-two participants with impaired glucose homeostasis undergoing LSG (body mass index 50.1 kg/m 2 , glycated hemoglobin 53 mmol/mol) were studied. Measurements of fasting and 120-minute TBARS and TAOS were performed during an oral glucose tolerance test preoperatively and postoperatively. Results Compared with preoperative levels, significant decreases were seen 6 months postoperatively in fasting TBARS (61.0±17.9 versus 39.4±13.8 ng/mL, P = .04) and 120-minute TBARS (76.0±29.5 versus 46.5±16.3 ng/mL, P = .02). No significant changes were observed in plasma TAOS. No significant association was observed between changes in TBARS and other clinical or biochemical measures. Conclusion We observed a significant reduction in TBARS, a global measure of lipid peroxidation 6 months after LSG in participants with obesity and impaired glucose regulation.

There are limited data to describe the relationship between the transvalvular gradient and mortality among patients who undergo aortic valve replacement.Using the National Echo Database Australia, valvular hemodynamics were characterized in 3,943 men (mean age, 62 ± 18 years) and 2,107 women (mean age, 62 ± 19 years) who underwent aortic valve replacement (median follow-up duration, 770 days; interquartile range, 381-1,584 days). The degree of impaired valvular hemodynamics (IVH) was categorized as mild (mean gradient 10.0-19.9 mm Hg, peak velocity 2.0-2.9 m/sec), moderate (mean gradient 20.0-39.9 mm Hg, peak velocity 3.0-3.9 m/sec), or severe (mean gradient ≥ 40.0 mm Hg, peak velocity ≥ 4 m/sec or effective orifice area0.8 cmOverall, 2,175 (36.0%), 2,598 (42.9%), 698 (11.5%), and 579 (9.6%) patients had no, mild, moderate, and severe IVH, respectively. Those with residual moderate or severe IVH had 5-year mortality of 45.5% and 57.3%, respectively, and higher adjusted long-term all-cause mortality (adjusted hazard ratios, 1.44 and 2.02; P .001) compared with "no IVH." Patients with mild IVH had similar mortality rates to those without IVH. A mortality threshold was evident above a mean transvalvular gradient22.5 mm Hg after adjusting for age, sex, stroke volume index, aortic regurgitation, and effective orifice area.After aortic valve replacement, most patients displayed an acceptable aortic valve hemodynamic profile. Moderate to severe IVH, however, was associated with poor long-term survival, with a threshold for increased mortality similar to that of native valvular aortic stenosis evident.

Background Bariatric surgery is an effective treatment for morbid obesity and metabolic dysfunction. Objectives The aim of this work was to examine the early temporal effects of laparoscopic sleeve gastrectomy (LSG) on adipokines (adiponectin, leptin), inflammatory cytokines (interleukin-6, C-reactive protein, interleukin-10), and global plasma measures of oxidative stress (thiobarbituric acid reactive substances and total antioxidant status) in a sample of 55 participants preoperatively, and 1 and 6 months postoperatively. The focus was on a sample of patients with impaired glucose tolerance and type 2 diabetes, which is associated with increased low-grade systemic inflammation and oxidative stress. Setting University hospital, United Kingdom. Methods This was a prospective study comprising 55 participants with impaired glucose homeostasis and type 2 diabetes undergoing LSG (mean body mass index 50.4 kg/m2, mean glycated hemoglobin 7.4%). Serial measurements of the above markers were made preoperatively, 1 and 6 months postoperatively (43 had measurable cytokines and oxidative stress at 1- and 6-mo follow-up). Results We observed a significant reduction in interleukin-6, C-reactive protein, leptin, and thiobarbituric acid reactive substances, along with an increase in adiponectin 6 months postoperatively. Conclusions To our knowledge the effects of LSG on inflammatory cytokines and plasma markers of oxidative stress have not been examined temporally in a sizeable sample of participants who have undergone LSG. This present study supports the role of LSG for the treatment of the proinflammatory and pro-oxidant status associated with obesity-related glucose dysregulation.

Present recommendations by the US Food and Drug Administration advise that patients with prolactinoma treated with cabergoline should have an annual echocardiogram to screen for valvular heart disease. Here, we present new clinical data and a systematic review of the scientific literature showing that the prevalence of cabergoline-associated valvulopathy is very low. We prospectively assessed 40 patients with prolactinoma taking cabergoline. Cardiovascular examination before echocardiography detected an audible systolic murmur in 10% of cases (all were functional murmurs), and no clinically significant valvular lesion was shown on echocardiogram in the 90% of patients without a murmur. Our systematic review identified 21 studies that assessed the presence of valvular abnormalities in patients with prolactinoma treated with cabergoline. Including our new clinical data, only two (0·11%) of 1811 patients were confirmed to have cabergoline-associated valvulopathy (three [0·17%] if possible cases were included). The probability of clinically significant valvular heart disease is low in the absence of a murmur. On the basis of these findings, we challenge the present recommendations to do routine echocardiography in all patients taking cabergoline for prolactinoma every 12 months. We propose that such patients should be screened by a clinical cardiovascular examination and that echocardiogram should be reserved for those patients with an audible murmur, those treated for more than 5 years at a dose of more than 3 mg per week, or those who maintain cabergoline treatment after the age of 50 years.

Described herein is a first-in-man attempt to both genetically modify T cells with an imagable suicide gene and track these transduced donor T cells in allogeneic stem cell transplantation recipients using noninvasive positron emission tomography/computerized tomography (PET/CT) imaging. A suicide gene encoding a human CD34-Herpes Simplex Virus-1-thymidine kinase (CD34-TK75) fusion enabled enrichment of retrovirally transduced T cells (TdT), control of graft-versus-host disease and imaging of TdT migration and expansion in vivo in mice and man. Analysis confirmed that CD34-TK75-enriched TdT contained no replication competent γ-retrovirus, were sensitive to ganciclovir, and displayed characteristic retroviral insertion sites (by targeted sequencing). Affinity-purified CD34-TK75(+)-selected donor T cells (1.0-13 × 10(5))/kg were infused into eight patients who relapsed after allogeneic stem cell transplantation. Six patients also were administered 9-[4-((18)F)fluoro-3-hydroxymethyl-butyl]guanine ([(18)F]FHBG) to specifically track the genetically modified donor T cells by PET/CT at several time points after infusion. All patients were assessed for graft-versus-host disease, response to ganciclovir, circulating TdT cells (using both quantitative polymerase chain reaction and [(18)F]FHBG PET/CT imaging), TdT cell clonal expansion, and immune response to the TdT. This phase 1 trial demonstrated that genetically modified T cells and [(18)F]FHBG can be safely infused in patients with relapsed hematologic malignancies after allogeneic stem cell transplantation.

Background Athlete ECG screening has been recommended by several international sporting bodies; however, a number of controversies remain regarding the accuracy of ECG screening. An important component that has not been assessed is the reproducibility of ECG interpretation. Objective The purpose of this study was to assess the variability of ECG interpretation among experienced physicians when screening a large number of athletes. Methods A sports cardiologist, a sports medicine physician, and an electrophysiologist analyzed 440 consecutive screening ECGs from asymptomatic athletes and were asked to classify the ECGs according to the 2010 European Society of Cardiology criteria as normal (or demonstrating training related ECG changes) or abnormal. When an abnormal ECG was identified, they were asked to outline what follow-up investigations they would recommend. Results The reported prevalence of abnormal ECGs ranged from 13.4% to 17.5%. Agreement on which ECGs were abnormal ranged from poor (κ = 0.297) to moderate (κ = 0.543) between observers. Suggested follow-up investigations were varied, and follow-up costs ranged from an additional A$30–A$129 per screening episode. Neither of the 2 subjects (0.45%) in the cohort with significant pathology diagnosed as a result of screening were identified correctly by all 3 physicians. Conclusion Even when experienced physicians interpret athletes' ECGs according to current standards, there is significant interobserver variability that results in false-positive and false-negative results, thus reducing the effectiveness and increasing the social and economic cost of screening.

Background Bariatric surgery is an effective treatment for morbid obesity. Obesity and type 2 diabetes are associated with chronic inflammation. There is lack of data examining the effects of sleeve gastrectomy (SG) on inflammatory biomarkers. Our aim was to study the effects of SG on specific cytokines associated with obesity including interleukin-6 (IL-6), interleukin-10 (IL-10), leptin, adiponectin, and C-reactive protein (CRP) preoperatively, 1 and 6 months after surgery. Methods A nonrandomized prospective study comprising of 22 participants with impaired glucose homeostasis and type 2 diabetes undergoing SG (body mass index 50.1 kg/m 2 , glycated hemoglobin [HbA1c] 53 mmol/mol). Serial measurements of IL-6, IL-10, leptin, adiponectin, and CRP were performed during oral glucose tolerance testing preoperatively, 1 and 6 months postoperatively. Results We observed significant improvements at 1 and 6 months in leptin ( P ≤.001) and CRP ( P = .003) after SG. We also observed a significant reduction in IL-6 at 6 months ( P = .001). No statistically significant differences were observed for adiponectin and IL-10. Conclusion This study is the first to examine the detailed changes in the inflammatory cytokines after SG. Our study shows significant improvements in the inflammatory biomarkers after SG in patients with impaired glucose homeostasis and type 2 diabetes.

Most data assessing the accuracy of electrocardiographic (ECG) screening in identifying cardiac pathology in athletes are derived from relatively unselected cohorts of subjects involved in competitive sports. We hypothesized that the prevalence of ECG abnormalities may be greater in athletes performing the greatest combination of exercise intensity and duration, namely professional endurance athletes. A total of 1,007 male and 254 female elite adult athletes underwent cardiovascular screening inclusive of an electrocardiogram, interpreted using the 2010 European Society of Cardiology guidelines. Training-related ECG changes (group 1) were more common in endurance athletes (EAs) than nonendurance athletes (NEAs; 90.8% vs 86.0%, p = 0.04), as were multiple (≥2) training-related changes (78.9% vs 53.5%, p

Aims To assess the incidence and progression of diabetic retinopathy (DR) 12months post bariatric surgery in persons with morbid obesity and type 2 diabetes. Methods A retrospective pilot analysis of electronic hospital records between 1998 and 2012. Results 40 of 148 subjects had pre- and post-surgery DR screening. Of those without DR pre-surgery 1.5% (n=26) progressed to minimum background DR (BDR) post surgery. Those with minimum BDR (n=9) pre-surgery revealed no progression, with 55.6% (n=5) showing evidence of regression. One person with moderately severe BDR and two with pre-proliferative DR (PPDR) prior to surgery experienced progression. Two persons with PPDR prior to surgery remained under the hospital eye services and were therefore not eligible to be re-assessed by the screening service. Conclusions There was a low incidence of new DR and progression of DR in those either without evidence of retinopathy or with minimal BDR prior to surgery with some subjects showing evidence of regression. There was however a risk of progression of DR in those with moderate BDR or worse, and should therefore be monitored closely post-surgery.

Current surgical management of restrictive ischaemic mitral regurgitation (IMR) includes mitral valve annuloplasty (MVA) using an undersized ring when the mechanism is secondary to leaflet restriction. In our experience, MVA alone is inadequate to eliminate mitral incompetence in these patients. We report the 'Down-Under Repair' as an adjunctive concept for the treatment of a subset of patients with restrictive IMR and associated inferobasal left ventricular aneurysm. The 'Down-Under Repair' reduces mitral leaflet restriction by approximating the origin of the posterior papillary muscle towards the mitral annulus. Midterm results demonstrated sustained valvular competence and symptomatic improvement.

We assessed left ventricular dysfunction in a population at high risk for heart failure (HF), and explored associations between ventricular function, HF risk factors and NT-proB natriuretic peptide (NT-proBNP).3550 subjects at high risk for incident HF (≥60 years plus ≥1 HF risk factor), but without pre-existing HF or left ventricular dysfunction, were recruited. Anthropomorphic data, medical history and blood for NT-proBNP were collected. Participants at highest risk (n = 664) (NT-proBNP highest quintile;30.0 pmol/L) and a sample (n = 51) from the lowest NT-proBNP quintile underwent echocardiography. Participants in the highest NT-proBNP quintile, compared to the lowest, were older (74 years vs. 67 years; p0.001) and more likely to have coronary artery disease, stroke or renal impairment. In the top NT-proBNP quintile (n = 664), left ventricular systolic impairment was observed in 6.6% (95% CI: 4 to 8%) of participants and was associated with male gender, coronary artery disease, hypertension and NT-proBNP. At least moderate diastolic dysfunction was observed in 24% (95% CI 20 to 27%) of participants and was associated with diabetes and NT-proBNP. In this high risk population, NT-proBNP was associated with left ventricular systolic impairment (p0.001) and moderate to severe diastolic dysfunction (p0.001) after adjustment for age, gender, coronary artery disease, diabetes, hypertension and obesity.A high burden of ventricular dysfunction was observed in this high risk group. Combining NT-proBNP and HF risk factors may identify those with ventricular dysfunction. This would allow resources to be focused on those at greatest risk of progression to overt HF.

Sudden cardiac death in young athletes is rare but tragic. The cardiology community is faced with the challenge of providing a sensible strategy for the prevention of SCD while simultaneously reaffirming that the benefits of regular exercise far outweigh potential risks. At present, there is a broad range of screening recommendations dependent upon country, sporting discipline, and competition level. While much recent debate has focused on the efficacy of screening with electrocardiography, a number of sporting bodies also mandate the inclusion of exercise testing and echocardiography in screening protocols. Cardiac magnetic resonance imaging, coronary calcium scoring and computed tomography coronary angiography have also been promoted as potentially valuable screening tools for competitive athletes. This review will examine the controversial topic of utilizing cardiac imaging for athlete pre-participation screening. Specifically, the limitations of screening for relatively rare disorders using imaging tools with uncertain or imperfect accuracy will be addressed. Current evidence suggests that the accuracy of all cardiac imaging modalities is insufficient to justify their use as primary screening modalities in athletes. Atypical findings such as marked cardiac dilation, reduced deformation, or small patches of delayed gadolinium enhancement may be commonly encountered in well-trained athletes, but, at present, the prognostic significance of such findings is unknown. Resulting uncertainty for the clinician and athlete has the potential for psychological stress, further testing, and unnecessary exclusions from competition. However, these concerns must not be confused with the extremely useful applications of cardiac imaging for the assessment of athletes with symptoms, an abnormal electrocardiogram or a positive family history. As modern imaging further enhances our understanding of the spectrum of athlete's heart, its role may expand from the assessment of athletes with suspected disease to being part of comprehensive pre-participation screening in apparently healthy athletes.

Background Myocardial microvascular dysfunction has been implicated in the pathogenesis of myocardial infarction (MI). We tested the hypothesis that patients with MI have lower microvasculature density in myocardium remote from the site of infarction than patients with similar extent of coronary artery disease (CAD) without MI and examined the relationship between myocardial capillary length density and plasma levels of angiogenesis-related biomarkers. Methods We analyzed biopsies from non-ischemic left ventricular (LV) myocardium and measured plasma levels of angiogenesis-related biomarkers in patients undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI) and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV without CAD. Results Myocardial microvascular density of NSTEMI patients was approximately half the density of no-MI patients, and similar to AS patients. Whereas the reduced microvascular density of AS patients was accounted for by their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV, and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine and low molecular weight fluorophores, higher vascular endothelial growth factor (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth factor levels than no-MI patients. Conclusions Recent MI was associated with reduced microvasculature density in myocardium remote from the site of infarction and alteration in plasma levels of angiogenesis-related biomarkers.

A 40 year-old woman presented to hospital with 12 h of progressive shortness of breath. She was 11 days postpartum, having delivered a full-term male infant. She was discharged on antibiotics for presumed pneumonia, but represented two days later with NYHA class IV symptoms and in acute decompensated heart failure confirmed on clinical examination and chest X-ray. Echocardiography showed a left ventricular ejection fraction (LVEF) of 20%. She was treated for peripartum cardiomyopathy (PPCM) with angiotensin converting enzyme inhibitors (ACEi), beta-blockers and diuretics with normalisation of her cardiac function within six months. Four years later, her son was diagnosed with Duchenne muscular dystrophy (DMD) and she tested positive as a carrier of the mutant gene. It is unclear whether the DMD carrier state alone is associated with increased susceptibility to PPCM or if this is merely the first expression of cardiomyopathy in a previously asymptomatic carrier.

Patients presenting with a syndrome of chest pain, elevated cardiac enzyme levels with or without electrocardiogram changes are a common diagnostic and management problem in cardiology. Most commonly, this is due to ischaemic myocardial infarction secondary to coronary artery disease. However, when coronary angiography does not demonstrate any obstructive coronary artery lesion, the diagnosis of myocarditis should be considered. Cardiac magnetic resonance imaging is helpful towards making this diagnosis. Here, we describe the first reported Australian cases of recurrent myocarditis presenting with ischaemic chest pain and elevated cardiac enzyme levels. These cases serve as an important reminder to clinicians that myocarditis is an important mimic of ischaemic myocardial infarction.

Surgical ventricular restoration (SVR) was conceived to improve hemodynamic and clinical outcomes in ischemic cardiomyopathy. The Surgical Treatment of Ischemic Heart Failure (STICH) trial has conclusively shown no additional benefits of SVR when routinely combined with coronary artery bypass surgery. However, the STICH study did not include a registry arm for SVR-eligible patients who were not randomized. This study describes the SVR experience in a single center when participating in the STICH study, to better understand the role of SVR in current clinical practice.All patients receiving SVR between 2002 and 2006 were prospectively followed. Patients were divided into STICH SVR (SSVR) and non-STICH SVR (NSSVR) groups. The SSVR patients received SVR as randomized in STICH. The NSSVR patients were evaluated for eligibility to participate in the STICH trial, and the reasons for not participating were analyzed. Baseline demographics, echocardiographic data, and clinical outcomes were compared.Nine NSSVR patients were compared with 12 SSVR patients. Only 1 NSSVR patient did not fulfill entry criteria into the STICH trial for randomization. The main reason for performing SVR outside of the STICH study was dominant heart failure symptom associated with enlarged left ventricle. The NSSVR group had more anterior wall asynergy (60% vs 45%, p0.001), larger preoperative heart volumes (left ventricular end-diastolic volume index 108 mL/m(2) vs 69 mL/m(2), p0.05) and larger volume reductions (34% vs 11%, p = 0.06). At 6.5-year follow-up, 83% SSVR and 89% NSSVR patients are alive.At our institution, patients eligible but not randomized into STICH, had larger preoperative heart volumes and larger volume reduction with SVR. The STICH study may not have included patients most likely to benefit from SVR.

Three priority areas in the prevention, diagnosis and management of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) were identified and discussed in detail: 1. Echocardiography and screening/diagnosis of RHD – Given the existing uncertainty it remains premature to advocate for or to incorporate echocardiographic screening for RHD into Australian clinical practice. Further research is currently being undertaken to evaluate the potential for echocardiography screening. 2. Secondary prophylaxis – Secondary prophylaxis (long acting benzathine penicillin injections) must be seen as a priority. Systems-based approaches are necessary with a focus on the development and evaluation of primary health care-based or led strategies incorporating effective health information management systems. Better/novel systems of delivery of prophylactic medications should be investigated. 3. Management of advanced RHD – National centres of excellence for the diagnosis, assessment and surgical management of RHD are required. Early referral for surgical input is necessary with multidisciplinary care and team-based decision making that includes patient, family, and local health providers. There is a need for a national RHD surgical register and research strategy for the assessment, intervention and long-term outcome of surgery and other interventions for RHD.

Glutathione peroxidase-1 (GPx-1) is an endogenous anti-oxidant enzyme. The T allele of the GPx-1 rs1050450 (C > T) gene variant is associated with reduced enzyme activity. Our aim was to examine the association between this gene variant and peripheral neuropathy in two cross-sectional samples of subjects with diabetes: (i) 773 Caucasian subjects were genotyped from the UCL Diabetes and Cardiovascular disease Study (UDACS) and (ii) 382 Caucasian subjects from the Ealing Diabetes Study (EDS). Peripheral neuropathy status (and oxidised-LDL [Ox-LDL:LDL] and plasma Total Ant-ioxidant Status [TAOS] in UDACS), were analysed in relation to genotype. We observed that: (i) In UDACS, the odds ratio (OR) for peripheral neuropathy in the T allele carriers compared to the CC genotype was 1.61 [1.10-2.28], p = 0.01. This remained significant after adjustment for other risk factors. Ox-LDL:LDL ratio was significantly elevated in T allele carriers (CC vs. CT/TT: 16.3 ± 2.4 v 18.0 ± 2.9 U/mmol LDL, p = 0.02). (ii) In EDS, the OR for peripheral neuropathy in the T allele carriers compared to the CC genotype was 1.95 [1.11-3.42], p = 0.02. This remained significant after adjustment for other risk factors. In conclusion, we observed a significant association between the T allele and peripheral neuropathy and LDL oxidation. This is the first paper to examine the rs1050450 variant in two samples of Caucasian subjects with diabetes. Prospective analysis of the gene variant is required in diabetic and healthy cohorts with measured plasma markers of oxidative stress to investigate the described association further.

Posttraumatic growth (PTG) is frequently reported after the strike of a serious medical illness. The current study sought to: 1) assess the relationship between degree of cardiac "threat" and PTG one-year post-hospitalization; and 2) to explore the association between PTG and healthcare utilization.In a cohort study, 2636 cardiac inpatients from 11 Ontario hospitals completed a sociodemographic survey; clinical data were extracted from charts. One year later, 1717 of these outpatients completed a postal survey, which assessed PTG and healthcare utilization. Morbidity data were obtained retrospectively through probabilistic linkage to administrative data. The predicted risk of recurrent events for each participant was calculated using a logistic regression model, based on participants' sociodemographic and clinical characteristics. The relationship among PTG, trauma and health service use was examined with multiple regression models.Greater PTG was significantly related to greater predicted risk of recurrent events (p0.001), but not the actual rate of recurrent events (p=0.117). Moreover, greater PTG was significantly related to more physician visits (p=0.006), and cardiac rehabilitation program enrolment (p=0.001) after accounting for predicted risk and sociodemographic variables. PTG was not related to urgent healthcare use.Greater PTG was related to greater objective risk of morbidity but not actual morbidity, suggesting that contemplation about the risk of future health problems may spur PTG. Moreover, greater PTG was associated with seeking non-urgent healthcare. Whether this translates to improved health outcomes warrants future study.

Thousands of tons of crude caffeine are produced annually in the decaffeination of coffee. Crude caffeineis further purified to obtain pure caffeine, and the non-caffeine residue is typically discarded as waste. Inthe present study, we discovered that crude caffeine possessed unexpected bioactive properties. Crudecaffeine had potent hydrophilic antioxidant activity (145 l mol Trolox equivalent (TE)/g) and lipophilicantioxidant activity (66 l mol TE/g). It also inhibited cyclooxygenase-2 with a higher potency (IC 50 ,20 l g/ml) than 2-acetoxybenzoic acid (aspirin, IC 50 , 190 l g/ml). Crude caffeine increased glucose uptake1.45-fold in cultured human skeletal muscle cells and 2.20-fold in adipocytes. In contrast, pure caffeine,which accounts for approximately 90% of the crude caffeine mass, was found to possess negligible anti-oxidant activity and did not inhibit cyclooxygenase-2, nor stimulate glucose uptake. We believe crudecaffeine has potential health benefits and may serve as a novel functional ingredient in the food industry. 2011 Elsevier Ltd. All rights reserved.

Pre-participation screening of all competitive athletes is recommended in some countries and mandated in others to prevent sudden cardiac death in predisposed athletes. Whilst the prevalence of some conditions, which are screened for such as coronary artery anomalies and long QT syndromes, are stable across different populations, the prevalence of underlying conditions such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia shows considerable geographic variability. Evidence exists that screening reduces sudden death, but the potential negative impact of exclusion from sport has not been quantified. Australia has a high rate of participation in sport and needs to consider whether screening is feasible, effective and affordable. It is difficult to make this decision currently as there is little information about the scope of the problem in Australia and whether the prevalence of underlying conditions which predispose to sudden cardiac death is similar or different to that in other countries. We review the evidence for and against screening and propose that systematic collection of Australian data is required before routine pre-participation screening can be introduced in Australia.

Adiponectin is associated with inflammation and oxidative stress. Levels are reduced in type 2 diabetes mellitus and coronary heart disease. Conversely, levels are elevated in type 1 diabetes mellitus (T1DM) and associated with microalbuminuria and diabetic nephropathy. An explanation may be that elevated adiponectin in T1DM represents a beneficial counterregulatory response to disease. Our aim was to examine adiponectin in relation to urinary albumin excretion and plasma total antioxidant status (TAOS) in subjects with long-standing T1DM. Serum adiponectin and plasma TAOS were measured in 338 samples from the Golden Years cohort. These subjects have T1DM for at least 50 years and are at low risk of complications. Subjects were divided into normoalbuminuria, microalbuminuria, and macroalbuminuria groups. Adiponectin was elevated in women (20.53 ± 5.94 vs 11.8 ± 3.6 mg/L, P < .001); therefore, the samples were sex stratified. Within men, adiponectin was higher in those with macroalbuminuria (normoalbuminuria vs microalbuminuria vs macroalbuminuria: 10.97 ± 3.26 vs 11.55 ± 3.50 vs 23.63 ± 7.07 mg/L, P = .002). In women, no difference was observed (20.48 ± 5.61 vs 20.75 ± 7.04 vs 29.62 ± 7.81 mg/L, respectively; P = .42). Plasma TAOS did not differ by groups. The correlation between adiponectin and TAOS showed a linear increase from normoalbuminuria, microalbuminuria, to macroalbuminuria in men (r = 0.33, P = .001; r = 0.48, P < .001; r = 0.59, P = .04) and women (r = 0.25, P = .01; r = 0.63, P < .001; r = 0.79, P = .08). Adiponectin was higher in women. Within men, levels were significantly higher in the presence of macroalbuminuria. In both sexes, adiponectin and TAOS were correlated, which was most marked with micro-/macroalbuminuria. The increase in adiponectin in the face of an insult may be a compensatory mechanism to reduce oxidative burden.

We hypothesized that consumption of soy protein isolate (SPI) or the soy isoflavone genistein (GEN) would modulate mRNA expression of genes underlying lipid and thyroid hormone metabolism in livers and small intestines of young adult male Sprague–Dawley rats. Early pregnant rat dams were placed on AIN-93G diets containing casein (CAS, control protein), SPI, or CAS+GEN. Litters were weaned to the same diet as their dam. SPI-fed (but not GEN-fed) male rats of 48 days of age had significant reductions in body weight, abdominal fat pad weight and hepatic content of lipid droplets and triglycerides. Hepatic peroxisome proliferator-activated receptor α ( Ppara ) transcripts were elevated with SPI but not GEN diet. Hepatic pyruvate dehydrogenase kinase-4 ( Pdk4 ) and cytochrome P450 4A10 ( Cyp4a10 ) mRNA abundance was reduced with SPI; the SPI effect on Cyp4a10 was recapitulated by GEN diet. SPI (but not GEN) suppressed Pdk4 and 3-hydroxy-3-methylglutaryl-CoA synthase 2 ( Hmgcs2 ) mRNA abundance in duodenum. Liver iodothyronine deiodinase types 1 and 2 ( Dio1 and Dio2 ) mRNA levels were increased with SPI diet; the effect on Dio2 , but not Dio1 mRNAs, also was observed with GEN. SPI and GEN increased hepatic types 1 and 2 iodothyronine deiodinase (D1 and D2) activities. Effects of SPI and GEN on the above gene expression may contribute to the observed reductions in body and adipose tissue weight and liver lipid content in this model. Identification of the regulation, by genistein and soy protein, of iodothyronine deiodinase synthesis has potential applications for treatment and prevention of fatty liver disease and obesity.

Burkholderia thailandensis is a less virulent close relative of Burkholderia pseudomallei, a CDC category B biothreat agent. We have previously shown that lipopolysaccharide (LPS) extracted from B. pseudomallei can provide protection against a lethal challenge of B. pseudomallei in a mouse model of melioidosis. Sugar analysis on LPS from B. thailandensis strain E264 confirmed that this polysaccharide has a similar structure to LPS from B. pseudomallei. Mice were immunised with LPS from B. thailandensis or B. pseudomallei and challenged with a lethal dose of B. pseudomallei strain K96243. Similar protection levels were observed when either LPS was used as the immunogen. This data suggests that B. thailandensis LPS has the potential to be used as part of a subunit based vaccine against pathogenic B. pseudomallei.