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Background: Rural patients with atherosclerotic cardiovascular disease (ASCVD) experience greater cardiovascular morbidity and mortality than their urban counterparts. Statin therapy is a key component of ASCVD treatment. The extent to which there may be regional differences in long-term adherence to statins is unknown., Objective: To assess long-term rates of adherence to statins in a high-risk ASCVD cohort, and whether regional differences exist between rural and urban patients., Methods: Follow-up was conducted in patients who underwent coronary angiography at a single tertiary center between 2009 and 2013. Adherence was defined as consumption of prescribed statin ≥6 days per week. Patients were divided into remoteness areas (RAs), classified as RA1 (major city), RA2 (inner regional), and RA3 (outer regional) based on the Australian Standard Geographical Classification., Results: Five hundred twenty-five patients (69% male, mean age 64 ± 11 years) were followed-up after a median of 5.3 years. Baseline characteristics were similar between RAs. Overall adherence was 83%; however, rural patients were significantly more adherent to their statin therapy (80% in RA1, 83% in RA2, and 93% in RA3, P = .04). Living in RA3 independently predicted greater statin adherence than living in RA1 (odds ratio: 2.75, 95% CI: 1.1-7.8, P = .03). All-cause mortality was significantly higher in RA3 than other regional areas (6% RA1, 12% RA2, and 18% RA3, P = .01)., Conclusions: Despite higher all-cause mortality, rural patients with ASCVD demonstrate significantly greater long-term adherence to statins than urban patients. Other factors, such as reduced access to health care and delayed diagnosis may explain the gap in outcomes between rural and urban patients., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

This feature article for the thematic series on congestive heart failure (CHF) readmissions aims to outline important gaps in guidelines for patients with multiple comorbidities and the elderly. Congestive heart failure diagnosis manifests as a 3-phase journey between the hospital and community, during acute, chronic stable, and end-of-life (palliative) phases. This journey requires in variable intensities a combination of multidisciplinary care within tertiary hospital or ambulatory care from hospital outpatients or primary health services, within the general community. Management goals are uniform, ie, to achieve the lowest New York Heart Association class possible, with improvement in ejection fraction, by delivering gold standard therapies within a CHF program. Comorbidities are an important common denominator that influences outcomes. Comorbidities include diabetes mellitus, chronic obstructive airways disease, chronic renal impairment, hypertension, obesity, sleep apnea, and advancing age. Geriatric care includes the latter as well as syndromes such as frailty, falls, incontinence, and confusion. Many systems still fail to comprehensively achieve all aspects of such programs. This review explores these factors., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background The relationship between mitral valve prolapse ( MVP ) and sudden cardiac death ( SCD ) remains controversial. In this systematic review, we evaluate the relationship between isolated MVP and SCD to better define a potential high-risk subtype. In addition, we determine whether premortem parameters could predict SCD in patients with MVP and the incidence of SCD in MVP . Methods and Results Electronic searches were conducted in PubMed and Embase for all English literature articles published between 1960 and 2018 regarding MVP and SCD or cardiac arrest. We also identified articles investigating predictors of ventricular arrhythmias or SCD and cohort studies reporting SCD outcomes in MVP . From 2180 citations, there were 79 articles describing 161 cases of MVP with SCD or cardiac arrest. The median age was 30 years and 69% of cases were female. Cardiac arrest occurred during situations of stress in 47% and was caused by ventricular fibrillation in 81%. Premature ventricular complexes on Holter monitoring (92%) were common. Most cases had bileaflet involvement (70%) with redundancy (99%) and nonsevere mitral regurgitation (83%). From 22 articles describing predictors for ventricular arrhythmias or SCD in MVP , leaflet redundancy was the only independent predictor of SCD . The incidence of SCD with MVP was estimated at 217 events per 100 000 person-years. Conclusions Isolated MVP and SCD predominantly affects young females with redundant bileaflet prolapse, with cardiac arrest usually occurring as a result of ventricular arrhythmias. To better understand the complex relationship between MVP and SCD , standardized reporting of clinical, electrophysiological, and cardiac imaging parameters with longitudinal follow-up is required.

Aim: Levels of plasma markers of myocardial fibrosis (galectin-3), stretch (B-type natriuretic peptide (BNP)) and injury (high-sensitivity troponin T (hs-TnT)) are affected by haemodialysis, residual renal function (RRF) and cardiac pathology. We aimed to determine the association of RRF, urine output and haemodialysis itself on cardiac biomarkers in haemodialysis patients., Methods: Adult haemodialysis patients underwent venesection pre- and post-haemodialysis then echocardiography and inter-dialytic urine collection to calculate RRF (mL/min per 1.73m 2 ) and urine output (mL/day). Galectin-3, BNP-32, NT-ProBNP and hs-TnT levels were compared across tertiles of echocardiographic parameters, RRF and urine output using the non-parametric test for trend across ordered groups., Results: Twenty-three patients (17 male) with mean age 67.7±13.8 years and median (interquartile range) dialysis duration 13.6 (9.8-19.1) months participated. Galectin-3 was substantially lower following haemodialysis: 55 ng/mL (47-70) versus 23 ng/mL (19-27, P < 0.001), but other biomarkers changed little. By increasing RRF tertile, post-dialysis galectin-3 was 32.6 ng/mL (23.7-36.6), 21.9 ng/mL (19.0-23.2) and 19.0 ng/mL (16.9-21.0, P = 0.001); NT-ProBNP was 10 192 ng/L (2303-21 504), 2037 ng/L (1224-10 795) and 1481 ng/L (172-2890, P = 0.016). Results were similar for daily urine volume, but measured echocardiographic parameters were not associated with biomarker concentrations., Conclusion: Plasma concentration of galectin-3 is reduced by the haemodialysis procedure. Lower RRF and urine volume are strongly associated with higher levels of galectin-3 and NT-Pro-BNP. These associations are important to the clinical interpretation of these biomarker levels in haemodialysis patients., (© 2017 Asian Pacific Society of Nephrology.)

Objective: Depression exacerbates the burden of heart failure and independently predicts mortality. The aim of this study was to investigate which specific symptoms of depression predict all-cause mortality in systolic heart failure patients., Methods: Consecutive outpatients with heart failure and impaired left ventricular ejection fraction (LVEF), attending an Australian metropolitan heart function clinic between 2001 and 2011, were enrolled. The Cardiac Depression Scale (CDS) was completed as a component of usual care. Baseline clinical characteristics were drawn from hospital databases. The primary end-point was all-cause mortality, obtained from the Australian National Death Index., Results: A total of 324 patients (68.5% male) were included (mean age at enrolment = 66.8 ± 14.36 years), with a median follow-up time of 6.7 years (95% CI 5.97-7.39) and a mortality rate of 50% by the census date. Mean LVEF = 31.0 ± 11.31%, with 25% having NYHA functional class of III or IV. Factor analysis of the CDS extracted six symptom dimensions: Hopelessness, Cognitive Impairment, Anhedonia/Mood, Irritability, Worry, and Sleep Disturbance. Cox regression analyses identified Hopelessness (HR 1.024, 95% CI 1.004-1.045, p = .018) and Cognitive Impairment (HR 1.048, 95% CI 1.005-1.093, p = .028) as independent risk markers of all-cause mortality, following adjustment of known prognostic clinical factors., Conclusion: Hopelessness and cognitive impairment are stronger risk markers for all-cause mortality than other symptoms of depression in systolic heart failure. These data will allow more specific risk assessment and potentially new targets for more effective treatment and management of depression in this population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The use of radial-artery grafts for coronary-artery bypass grafting (CABG) may result in better postoperative outcomes than the use of saphenous-vein grafts. However, randomized, controlled trials comparing radial-artery grafts and saphenous-vein grafts have been individually underpowered to detect differences in clinical outcomes. We performed a patient-level combined analysis of randomized, controlled trials to compare radial-artery grafts and saphenous-vein grafts for CABG., Methods: Six trials were identified. The primary outcome was a composite of death, myocardial infarction, or repeat revascularization. The secondary outcome was graft patency on follow-up angiography. Mixed-effects Cox regression models were used to estimate the treatment effect on the outcomes., Results: A total of 1036 patients were included in the analysis (534 patients with radial-artery grafts and 502 patients with saphenous-vein grafts). After a mean (±SD) follow-up time of 60±30 months, the incidence of adverse cardiac events was significantly lower in association with radial-artery grafts than with saphenous-vein grafts (hazard ratio, 0.67; 95% confidence interval [CI], 0.49 to 0.90; P=0.01). At follow-up angiography (mean follow-up, 50±30 months), the use of radial-artery grafts was also associated with a significantly lower risk of occlusion (hazard ratio, 0.44; 95% CI, 0.28 to 0.70; P<0.001). As compared with the use of saphenous-vein grafts, the use of radial-artery grafts was associated with a nominally lower incidence of myocardial infarction (hazard ratio, 0.72; 95% CI, 0.53 to 0.99; P=0.04) and a lower incidence of repeat revascularization (hazard ratio, 0.50; 95% CI, 0.40 to 0.63; P<0.001) but not a lower incidence of death from any cause (hazard ratio, 0.90; 95% CI, 0.59 to 1.41; P=0.68)., Conclusions: As compared with the use of saphenous-vein grafts, the use of radial-artery grafts for CABG resulted in a lower rate of adverse cardiac events and a higher rate of patency at 5 years of follow-up. (Funded by Weill Cornell Medicine and others.).

Background: Exercise confidence predicts exercise adherence in heart failure (HF) patients. The association between simple tests of functional capacity on exercise confidence are not known., Objectives: To evaluate the association between a single 6-min walk test (6MWT) and exercise confidence in HF patients., Methods: Observational study enrolling HF outpatients who completed the Cardiac Depression Scale and an Exercise Confidence Survey at baseline and following the 6MWT. Paired t-test was used to compare repeated-measures data, while Repeated Measures Analysis of Covariance was used for multivariate analysis., Results: 106 HF patients were enrolled in the study (males, 82%; mean age, 64 ± 12 years). Baseline Exercise Confidence was inversely associated with age (p < 0.01), NYHA class (p < 0.001), and depression (p < 0.001). The 6MWT was associated with an improvement in Exercise Confidence (F(1,92) = 5.0, p = 0.03) after adjustment for age, gender, HF duration, NYHA class and depression., Conclusions: The 6MWT is associated with improved exercise confidence in HF patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Chronic heart failure (CHF) is a common, debilitating condition associated with significant health and economic burden. CHF management is multidisciplinary, however, achieving better health relies on a collaborative effort and patient engagement in self-care. Despite the importance of self-care in CHF, many patients have poor adherence to their medical and lifestyle regimens, in particular with regards to engaging in physical exercise. The patient's confidence in their ability, otherwise known as self-efficacy, is an important determinant of CHF health outcomes, most likely due to its effect on the uptake of CHF self-care activities especially exercise initiation and maintenance. Self-efficacy is responsive to experience such as exercise training, however the critical components of exercise interventions to improve self-efficacy have yet to be determined. This narrative review provides an overview of the role of self-efficacy in exercise adherence in CHF., (Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

The symptom cluster of shortness of breath (SOB) contributes significantly to the outpatient workload of cardiology services. The workup of these patients includes blood chemistry and biomarkers, imaging and functional testing of the heart and lungs. A diagnosis of diastolic heart failure is inferred through the exclusion of systolic abnormalities, a normal pulmonary function test and normal hemoglobin, coupled with diastolic abnormalities on echocardiography. Differentiating confounders such as obesity or deconditioning in a patient with diastolic abnormalities is difficult. While the most recent guidelines provide more avenues for diagnosis, such as incorporating the left atrial size, little emphasis is given to understanding left atrial function, which contributes to at least 25% of diastolic left ventricular filling; additionally, exercise stress testing to elicit symptoms and test the dynamics of diastolic parameters, especially when access to the "gold standard" invasive tests is lacking, presents clinical translational gaps. It is thus important in diastolic heart failure work up to understand left atrial mechanics and the role of exercise testing to build a comprehensive argument for the diagnosis of diastolic heart failure in a patient presenting with SOB., Competing Interests: Conflict-of-interest statement: All co-authors have secured independent and governmental research funding. None pose a conflict of interest for this review.

Obesity, sedentary lifestyle and aging are associated with mitochondrial dysfunction and impaired insulin sensitivity. Acute exercise increases insulin sensitivity in skeletal muscle; however, whether mitochondria are involved in these processes remains unclear. The aim of this study was to investigate the effects of insulin stimulation at rest and after acute exercise on skeletal muscle mitochondrial respiratory function (JO2) and hydrogen peroxide emission (JH2O2), and the associations with insulin sensitivity in obese, sedentary men. Nine men (means ± SD: 57 ± 6 years; BMI 33 ± 5 kg.m2) underwent hyperinsulinemic-euglycemic clamps in two separate trials 1-3 weeks apart: one under resting conditions, and another 1 hour after high-intensity exercise (4x4 min cycling at 95% HRpeak). Muscle biopsies were obtained at baseline, and pre/post clamp to measure JO2 with high-resolution respirometry and JH2O2 via Amplex UltraRed from permeabilized fibers. Post-exercise, both JO2 and JH2O2 during ADP stimulated state-3/OXPHOS respiration were lower compared to baseline (P<0.05), but not after subsequent insulin stimulation. JH2O2 was lower post-exercise and after subsequent insulin stimulation compared to insulin stimulation in the rest trial during succinate supported state-4/leak respiration (P<0.05). In contrast, JH2O2 increased during complex-I supported leak respiration with insulin after exercise compared with resting conditions (P<0.05). Resting insulin sensitivity and JH2O2 during complex-I leak respiration were positively correlated (r = 0.77, P<0.05). We conclude that in obese, older and sedentary men, acute exercise modifies skeletal muscle mitochondrial respiration and H2O2 emission responses to hyperinsulinemia in a respiratory state-specific manner, which may have implications for metabolic diseases involving insulin resistance.

We have reported that calcitonin receptor (CTR) is widely expressed in biopsies from the lethal brain tumour glioblastoma by malignant glioma and brain tumour-initiating cells (glioma stem cells) using anti-human CTR antibodies. A monoclonal antibody against an epitope within the extracellular domain of CTR was raised (mAb2C4) and chemically conjugated to either plant ribosome-inactivating proteins (RIPs) dianthin-30 or gelonin, or the drug monomethyl auristatin E (MMAE), and purified. In the high-grade glioma cell line (HGG, representing glioma stem cells) SB2b, in the presence of the triterpene glycoside SO1861, the EC 50 for mAb2C4:dianthin was 10.0 pM and for mAb2C4:MMAE [antibody drug conjugate (ADC)] 2.5 nM, 250-fold less potent. With the cell line U87MG, in the presence of SO1861, the EC 50 for mAb2C4:dianthin was 20 pM, mAb2C4:gelonin, 20 pM, compared to the ADC (6.3 nM), which is >300 less potent. Several other HGG cell lines that express CTR were tested and the efficacies of mAb2C4:RIP (dianthin or gelonin) were similar. Co-administration of the enhancer SO1861 purified from plants enhances lysosomal escape. Enhancement with SO1861 increased potency of the immunotoxin (>3 log values) compared to the ADC (1 log). The uptake of antibody was demonstrated with the fluorescent conjugate mAb2C4:Alexa Fluor 568, and the release of dianthin-30:Alexa Fluor488 into the cytosol following addition of SO1861 supports our model. These data demonstrate that the immunotoxins are highly potent and that CTR is an effective target expressed by a large proportion of HGG cell lines representative of glioma stem cells and isolated from individual patients.

Background: Depression is common in patients with cardiovascular disease and is a risk marker for increased mortality. The valid and reliable detection of depression is fundamental to the appropriate management of these patients., Aim: The aim of this study was to evaluate the psychometric characteristics of the Cardiac Depression Scale Short Form 1 (DS-SF1) and the Cardiac Depression Scale Short Form 2 (DS-SF2) for screening cardiac outpatients in clinical settings., Methods: Adult cardiac outpatients attending a cardiovascular clinic completed the Cardiac Depression Scale (CDS), two versions of the DS-SF (DS-SF1 and DS-SF2) and the Physical Health Questionnaire 2 (PHQ2-Y/N) prior to their cardiac consultation., Results: Data from 326 patients (224 men; mean±SD age 66.25±14.39 years) were analysed. The DS-SF1 (mean score 16.28±5.70) had good construct validity with the CDS ( r=0.77; p<0.0001), adequate convergence with the PHQ2-Y/N ( r=0.59; p<0.0001) and good internal consistency (α=0.73). The DS-SF2 (mean score 15.80±6.80) had a better construct validity with the CDS ( r=0.84; p<0.0001) and the PHQ2-Y/N ( r=0.69; p<0.0001) and better internal consistency (α=0.82). The DS-SF2 showed strong criterion validity with the CDS with a DS-SF2 ⩾15 cut-point yielding 90% sensitivity and 73% specificity (area under the curve 0.92) for detecting depression (CDS ⩾95)., Conclusion: These findings confirm the excellent psychometric properties of the DS-SF2 as an ideal tool for screening depression in cardiac patients in clinical practice. The DS-SF2 should be regarded as the definitive version of the DS-SF.

Background: Psychological resilience is associated with an improved capacity to cope with chronic health challenges such as cardiovascular disease., Aims: The aim of this cross-sectional study was to examine the relationship between psychological resilience and symptoms of depression in a non-acute cardiac outpatient population., Methods: A total of 419 adult cardiac outpatients (288 men; mean±SD age 66.26±14.04 years) attending cardiovascular clinics completed the Sense of Coherence (SOC13) scale as a measure of psychological resilience and the Cardiac Depression Scale (CDS26) prior to their consultation., Results: The total SOC13 score (mean±SD 64.02±14.24, range 19-91) was within the moderate range. Older patients (⩾65 years) were significantly more resilient than those aged <65 ( p<0.01). Psychological resilience (SOC13) was negatively correlated with depression (CDS26) ( r=-0.79; p<0.001) and inversely associated with affective, cognitive and somatic symptoms of depression. Psychological resilience, particularly meaningfulness, accounted for more of the variance in affective features of depression than for somatic features., Conclusion: These findings show that low psychological resilience was related to depression in this cohort of cardiac outpatients, particularly affective symptoms such as anhedonia and hopelessness. The SOC13 scale offers a complementary measure of psychological status that could be used to monitor, and possibly predict, patient coping and response to treatment throughout the cardiovascular disease trajectory.

Background: Beta-blockers (BBs) are the mainstay prognostic medication for all stages of chronic heart failure (CHF). There are many classes of BBs, each of which has varying levels of evidence to support its efficacy in CHF. However, most CHF patients have one or more comorbid conditions such as diabetes, renal impairment, and/or atrial fibrillation. Patient enrollment to randomized controlled trials (RCTs) often excludes those with certain comorbidities, particularly if the symptoms are severe. Consequently, the extent to which evidence drawn from RCTs is generalizable to CHF patients has not been well described. Clinical guidelines also underrepresent this point by providing generic advice for all patients. The aim of this review is to examine the evidence to support the use of BBs in CHF patients with common comorbid conditions., Methods: We searched MEDLINE, PubMed, and the reference lists of reviews for RCTs, post hoc analyses, systematic reviews, and meta-analyses that report on use of BBs in CHF along with patient demographics and comorbidities., Results: In total, 38 studies from 28 RCTs were identified, which provided data on six BBs against placebo or head to head with another BB agent in ischemic and nonischemic cardiomyopathies. Several studies explored BBs in older patients. Female patients and non-Caucasian race were underrepresented in trials. End points were cardiovascular hospitalization and mortality. Comorbid diabetes, renal impairment, or atrial fibrillation was detailed; however, no reference to disease spectrum or management goals as a focus could be seen in any of the studies. In this sense, enrollment may have limited more severe grades of these comorbidities., Conclusions: RCTs provide authoritative information for a spectrum of CHF presentations that support guidelines. RCTs may provide inadequate information for more heterogeneous CHF patient cohorts. Greater Phase IV research may be needed to fill this gap and inform guidelines for a more global patient population., Competing Interests: Authors disclose no potential conflicts of interest. Disclosure All co-authors have won independent and governmental research funding. Several members provide counsel to pharmaceuticals. None pose a conflict of interest for this review.

Purpose: The discrepancy between patient-desired outcomes and achievable functional outcomes is a source of patient dissatisfaction. This paper reports development and validation of a questionnaire to assess this discrepancy in patients undergoing knee replacement surgery., Methods: The initial questionnaire (Knee Surgery Perception Questionnaire, KSPQ) comprised two parts. Part A, assessed patients' perception of their current level of function and pain, and Part B, assessed patients' desired outcomes of the surgery. Validation was carried out for Part A and then applied to Part B using a one-factor congeneric model and was tested in 185 patients preceding surgery. A discrepancy score between patients' expectations and desired outcome (Part B) and their perception of current function (Part A) was also calculated. Pearson correlations were used between the KSPQ total score and subscales and other knee-specific questionnaires to determine construct validity., Results: The final best set of models included four items for each subscale with a Chi-square value of 7.3 (n.s). The subscales and the total KSPQ showed significant strong to moderate correlations with knee-specific questionnaires. The discrepancy score in each subscale and the overall score showed relatively large discrepancy between patients' expectations and their perception of current function; with higher discrepancy score reported for pain and walking., Conclusion: The KSPQ is a valid questionnaire to assess patients' expected and desired outcomes of knee replacement surgery and their perception of their current abilities and function, and discrepancy between these. The KSPQ now requires further investigation at different stages of recovery following surgery., Level of Evidence: III.

Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HR peak ; 2 min recovery periods), separated by 1-3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160 Ser588 , were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation ( r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion: These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE.

Background: Undercarboxylated osteocalcin (ucOC) increases insulin sensitivity in mice. In humans, data are supportive, but the studies are mostly cross-sectional. Exercise increases whole-body insulin sensitivity, in part via ucOC, while acute glucocorticoid treatment suppresses ucOC in humans and mice., Objectives: A single dose of prednisolone reduces the rise in ucOC produced by exercise, which partly accounts for the failed increase in insulin sensitivity following exercise., Methods: Healthy young men (n=12) aged 18 to 40 years will be recruited. Initial assessments will include analysis of fasting blood, body composition, aerobic power (VO2peak), and peak heart rate. Participants will then be randomly allocated, double-blind, to a single dose of 20 mg of prednisolone or placebo. The two experimental trials will involve 30 minutes of interval exercise (90%-95% peak heart rate), followed by 3 hours of recovery and 2 hours of euglycaemic- hyperinsulinaemic clamp (insulin clamp). Seven muscle biopsies and blood samples will be obtained at rest, following exercise and post-insulin clamps., Results: The study is funded by the National Heart Foundation of Australia and Victoria University. Enrollment has already commenced and data collection will be completed in 2016., Conclusion: If the hypothesis is confirmed, the study will provide novel insights into the potential role of ucOC in insulin sensitivity in human subjects and will elucidate pathways involved in exercise-induced insulin sensitivity.

Left ventricular diastolic dysfunction (LVDD) is one of the earliest signs for abnormal cardiac function in patients with type 2 diabetes (T2DM). It is important to explore the risk factors that will assist in identifying the severity of the LVDD in this population. We examined the influences of fitness and fatness on the level of left ventricular (LV) impairment in patients with T2DM. Twenty-five patients (age: 64.0 ± 2.5 years, body mass index [BMI] = 36.0 ± 1.5 kg/m(2), mean ± standard error of measurement) with T2DM and preserved systolic function, but impaired diastolic function, mitral valve (MV) E/e', participated in the study. LV function was assessed using a stress echocardiograph, aerobic power was assessed with a sign- and symptom-limited graded exercise test, and the fatness level was assessed using Dual-energy X-ray absorptiometry and BMI. Patients in the higher 50% of BMI had higher lateral and septal MV E/e' (∼34% and ∼25%, respectively, both P < 0.001), compared to those in the lower 50% of BMI, with no difference in LV ejection fraction (LVEF) (P > 0.05). In addition, a higher BMI correlated with a higher lateral (r = 0.62, P < 0.001) and septal (r = 0.56, P < 0.01) E/e'. There was no such relationship for VO2peak. BMI and VO2peak were not correlated with LV systolic function (ejection fraction). In individuals with T2DM and diastolic dysfunction, a higher BMI was associated with worsening diastolic function independent of their aerobic capacity. The data provide a simple and practical approach for clinicians to assist in the early identification and diagnostics of functional changes in the heart diastolic function in this population.

Unlabelled: Regression of atherosclerosis is a key aspect of preventing further coronary artery disease and understanding which cell type forms smooth muscle cells in atherosclerotic fibrous caps will aid in reducing CAD. Atherogenesis is a complex interplay of cells migrating and proliferating into the vascular wall. CD34 positive hemapoetic stem cells are believed to not transform into vascular smooth muscle cells (SMC). The current study hypothesised that there would be no evidence for CD34(+)/α SMC actin(+) cells in atherosclerotic coronary arteries., Aims: To identify CD34+/α actin positive cells in the fibrous cap and wall of atherosclerotic plaques in the coronary artery., Methods: Male New Zealand White rabbits were fed a diet containing 0.5% cholesterol and 1% methionine for 4 weeks, then 9 weeks of normal diet to induce regression. Immunohistochemistry was used to detect CD34(+) haematopoietic progenitor cells and α SMC actin., Results: In the fibrous cap, the majority of cells were CD34(-)/α SMC actin(+) spindle shaped cells. However very rare populations of CD34(+)/α SMC actin(+) and CD34(+)/α SMC actin(-) cells were also present but these cells were not spindle shaped., Conclusion: Our study found that CD34(+)/α SMC actin(-) spindle shaped cells were absent from the fibrous cap. Moreover, the predominant cell population were the vascular smooth muscle cells (CD34(-)/α SMC actin(+)) but (CD34(+)/α SMC actin(+)) cells were also present. This model could be used to understand the role of each SMC population subtype to hasten atherosclerotic regression in the coronary artery., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Importance: There is increasing evidence supporting the importance of psychosocial factors in the pathophysiology of atherosclerotic disease. They have been shown to be associated with the population attributable risk for myocardial infarction., Objective: To determine if a score of favorable childhood psychosocial factors would be associated with decreased coronary artery calcification in adulthood., Design, Setting, and Participants: The analyses were performed in 2015 using data gathered in 1980 and 2008 within the longitudinal Cardiovascular Risk in Young Finns Study. The data source consisted of 311 individuals who had psychosocial factors measured at ages 12 years to 18 years and coronary artery calcification measured 28 years later in adulthood. The summary measure of psychosocial factors in childhood comprised measures of socioeconomic factors, emotional factors, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child., Main Outcomes and Measures: Coronary artery calcification at ages 40 years to 46 years., Results: Of the 311 participants, 48.2% were men. Of the participants, 55 (17.7%) had some calcium observed in their coronary arteries. A 1-SD increase in a favorable summary score of childhood psychological factors was associated with an adulthood coronary artery calcification probability of 0.85 (95% CI, 0.76-0.95) (P = .006). This inverse relationship remained significant after adjustment for age, sex, and conventional childhood risk factors (0.85; 95% CI, 0.74-0.97; P = .02) or for age, sex, adulthood conventional cardiovascular risk factors, socioeconomic status, social support, and depressive symptoms (0.83; 95% CI, 0.71-0.97; P = .02)., Conclusions and Relevance: In this longitudinal study, we observed an independent association between childhood psychosocial well-being and reduced coronary artery calcification in adulthood. A positive childhood psychosocial environment may decrease cardiovascular risk in adulthood and may represent a potentially modifiable risk determinant.

Chronic heart failure (CHF) among Aboriginal/Indigenous Australians is endemic. There are also grave concerns for outcomes once acquired. This point is compounded by a lack of prospective and objective studies to plan care. To capture the essence of the presented topic it is essential to broadly understand Indigenous health. Key words such as 'worsening', 'gaps', 'need to do more', 'poorly studied', or 'future studies should inform' occur frequently in contrast to CHF research for almost all other groups. This narrative styled opinion piece attempts to discuss future directions for CHF care for Indigenous Australians. We provide a synopsis of the problem, highlight the treatment gaps, and define the impediments that present hurdles in optimising CHF care for Indigenous Australians.

Congestive heart failure (CHF) therapeutics is generated through a well-described evidence generating process. Phases 1 - 3 of this process are required prior to approval and widespread clinical use. Phase 3 in almost all cases is a methodologically sound randomized controlled trial (RCT). After this phase it is generally accepted that the treatment has a significant, independent and prognostically beneficial effect on the pathophysiological process. A major criticism of RCTs is the population to whom the result is applicable. When this population is significantly different from the trial cohort the external validity comes into question. Should the continuation of the evidence generating process continue these problems might be identified. Post marketing surveillance through phase 4 and comparative effectiveness studies through phase 5 trials are often underperformed in comparison to the RCT. These processes can help identify remote adverse events and define new hypotheses for community level benefits. This review is aimed at exploring the post-marketing scene for CHF therapeutics from an Australian health system perspective. We explore the phases of clinical trials, the level of evidence currently available and options for ensuring greater accountability for community level CHF clinical outcomes.

Muscle atrophy is caused by an imbalance in contractile protein synthesis and degradation which can be triggered by various conditions including Type 2 Diabetes Mellitus (T2DM). Reduced muscle quality in patients with T2DM adversely affects muscle function, the capacity to perform activities of daily living, quality of life and ultimately may increase the risk of premature mortality. Systemic inflammation initiated by obesity and prolonged overnutrition not only contributes to insulin resistance typical of T2DM, but also promotes muscle atrophy via decreased muscle protein synthesis and increased ubiquitin-proteasome, lysosomal-proteasome and caspase 3- mediated protein degradation. Emerging evidence suggests that the inflammation-sensitive Nuclear Factor κ B (NF-κB) and Signal Transducer and Activator of Transcription 3 (STAT3) pathways may contribute to muscle atrophy in T2DM. In contrast, exercise appears to be an effective tool in promoting muscle hypertrophy, in part due to its effect on systemic and local (skeletal muscle) inflammation. The current review discusses the role inflammation plays in muscle atrophy in T2DM and the role of exercise training in minimising the effect of inflammatory markers on skeletal muscle. We also report original data from a cohort of obese patients with T2DM compared to age-matched controls and demonstrate that patients with T2DM have 60% higher skeletal muscle expression of the atrophy transcription factor FoxO1. This review concludes that inflammatory pathways in muscle, in particular, NF-κB, potentially contribute to T2DM-mediated muscle atrophy. Further in-vivo and longitudinal human research is required to better understand the role of inflammation in T2DM-mediated atrophy and the anti-inflammatory effect of exercise training under these conditions., (Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.)

Congestive heart failure (CHF) is a chronic and often devastating cardiovascular disorder with no cure. There has been much advancement in the last two decades that has seen improvements in morbidity and mortality. Clinicians have also noted variations in the responses to therapies. More detailed observations also point to clusters of diseases, phenotypic groupings, unusual severity and the rates at which CHF occurs. Medical genetics is playing an increasingly important role in answering some of these observations. This developing field in many respects provides more information than is currently clinically applicable. This includes making sense of the established single gene mutations or uncommon private mutations. In this thematic series which discusses the many factors that could be relevant for CHF care, once established treatments are available in the communities; this section addresses a contextual role for medical genetics.

Psychosocial factors play an important role in the development and progression of cardiovascular diseases (CVD), such as chronic heart failure (CHF). In particular, psycho-cognitive disturbance is common in CHF, which presents additional challenges to secondary prevention and management strategies. This review provides a summary of the contemporary psycho-cardiology literature, including coverage of common mood and cognitive symptoms, and explores some of the pathophysiologic evidence linking psycho-cognition to CHF, with particular emphasis on sympathetic nervous system activation and neuroendocrine functioning. Social support is identified as a strategy by which to reduce depressive symptoms, manage cognitive impairment and to, potentially, improve health outcomes through improved patient self care and adherence. Recent research outcomes suggest that the integration of family caregivers into CHF psycho-educational disease management programs, as providers and recipients of support, may achieve best outcomes. In this regard, couples-oriented strategies that promote communication, emotional attachment and support may enhance healthpromoting behaviours in patients and their partners.

The role of an atherogenic diet in causing pulmonary fibrosis has received little attention and simvastatin has been shown to reduce pulmonary fibrosis in animal models. To determine if an atherogenic diet can induce pulmonary fibrosis and whether simvastatin treatment is beneficial by up-regulating heat shock protein 70 and 90. New Zealand white rabbits (n = 15) were divided: Group 1 (control); Group 2 (MC) received a normal rabbit diet with 1% methionine plus 0.5% cholesterol (atherogenic diet). Group 3 received the same diet as the MC group plus 5 mg/kg/day simvastatin orally (MCS). After 4 weeks, the lungs were collected and analysed. Picrosirus red staining of lung interstitial collagen content showed that the atherogenic diet increased fibrosis 2.9-fold (P < 0.05), bronchiole adventitial collagen was increased 2.3-fold (P < 0.05) and bronchiole epithelium was increased 34-fold (P < 0.05), and simvastatin treatment severely reduced this effect (P < 0.05). Western blot analysis showed that the atherogenic diet significantly reduced lung Hsp70 protein by 22% (P < 0.05) and Hsp90 protein by 18% (P < 0.05) and simvastatin treatment did not affect this result. However, aortic hyper-responsiveness to vasoconstrictors (angiotensin II and phenylephrine) were markedly reduced by simvastatin treatment. We report that an atherogenic diet stimulates pulmonary fibrosis and reduces lung Hsp70/Hsp90 protein concentration. Simvastatin impairs this by mechanisms unrelated to Hsp70/Hsp90, but possibly a reduction in angiotensin II receptor or alpha adrenergic receptor pathways. These results could have implications in idiopathic pulmonary fibrosis., (© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Chronic heart failure (CHF) is a progressive and debilitating disease with a broad symptom profile, intermittently marked by periods of acute decompensation. CHF patients are encouraged to self-manage their illness, such as adhering to medical regimens and monitoring symptoms, to optimise health outcomes and quality of life. In so doing, patients are asked to collaborate with their health service providers with regard to their care. However, patients generally do not self-manage well, even with specialist support. Moreover, self-management interventions are yet to demonstrate morbidity or mortality benefits. Social network approaches to self-management consider the availability and mobilisation of all resources, beyond those of only the patient and healthcare providers. Used in conjunction with e-health platforms, social network approaches may offer a means by which to optimise self-management programmes of the future., Competing Interests: Disclosure: The authors have no conflicts of interest to declare.

Background: Depression is common after a cardiac event; however it often remains untreated. Previously, we reported the efficacy and feasibility of a 6-month tele-health programme (MoodCare), which integrates depression management into a cardiovascular disease (CVD) risk reduction programme for Acute Coronary Syndrome (ACS) patients with low mood. Here, we evaluate the long-term efficacy of the programme at 12-month follow-up., Design: A two-arm, parallel, randomized design to compare the long-term effects of 'MoodCare' (n = 61) to usual care (UC) (n = 60) at 12 months., Method: 121 ACS patients recruited from six hospitals in Victoria and Brisbane, Australia were randomized to a telephone-delivered cognitive behavioural therapy and risk-reduction programme or usual medical care. Mixed-model repeated measurements (MMRM) analysis was applied with results expressed as estimated marginal mean changes in depression and health-related quality of life (HRQOL) outcomes by group., Results: After 12 months, treatment effects were observed for those with major depressive disorder (MDD) for PHQ-9 depression (MoodCare: mean score: 6.5; 95% CI: 4.9-8.0 versus UC: 9.3; 95% CI: 7.7-10.9, p = 0.012)) and SF-12 mental health scores (MoodCare: 42.5; 95% CI: 39.8-45.2 versus UC: 36.8; 95% CI: 34.1-39.6, p = 0.005). No beneficial treatment effects were observed in those with no MDD at baseline., Conclusion: After 12 months, MoodCare was superior to UC for improving mental health outcomes for those with a clinical diagnosis of major depression. Our findings support the implementation of depression-based interventions for cardiac patients with a clinical diagnosis of depression and provide evidence of longer term efficacy to one year., (© The European Society of Cardiology 2014.)

Bone remodelling markers (BRMs) are suppressed following a glucose load and during glucose infusion. As exercise increases indices of bone health and improves glucose handling, we hypothesised that, at rest, hyperinsulinaemic-euglycaemic clamp will suppress BRMs in obese men and that exercise prior to the clamp will prevent this suppression. Eleven obese nondiabetic men (age 58.1±2.2 years, body mass index=33.1±1.4 kg m(-2) mean±s.e.m.) had a hyperinsulinaemic-euglycaemic clamp (HEC) at rest (Control) and 60 min post exercise (four bouts × 4 min cycling at 95% of hazard ratiopeak). Blood samples were analysed for serum insulin, glucose, bone formation markers, total osteocalcin (tOC) and procollagen type 1 N-terminal propeptide (P1NP), and the bone resorption marker, β-isomerised C-terminal telopeptides (β-CTx). In the control trial (no exercise), tOC, P1NP and β-CTx decreased with HEC by >10% compared with baseline (P<0.05). Fasting serum glucose, but not insulin, tended to correlate negatively with the BRMs (β range -0.57 to -0.66, p range 0.051-0.087). β-CTx, but not OC or P1NP, increased within 60 min post exercise (∼16%, P<0.01). During the post-exercise HEC, the glucose infusion rate was ∼30% higher compared with the no exercise trial. Despite this, BRMs were only suppressed to a similar extent as in the control session (10%). HEC suppressed BRMs in obese men. Exercise did not prevent this suppression of BRMs by HEC but improved glucose handling during the trial. It remains to be tested whether an exercise intervention of longer duration may be able to prevent the effect of HEC on bone remodelling.

This position paper provide guidelines on the minimum requirements of both personnel and equipment for the safe performance of clinical exercise electrocardiography, and for the adequate interpretation and assessment of results. This document was originally developed by Professor Ben Freedman and members of the Rehabilitation, Exercise and Prevention Working Group in 1996. It has been recently reviewed by a Working Group chaired by Associate Professor David Colquhoun. The resulting, revised Statement was considered by the Continuing Education and Recertification Committee and ratified at the CSANZ Board meeting held on 1st August 2014., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Congestive Heart Failure (CHF) is an ambulatory care sensitive condition, associated with significant morbidity and mortality, rarely with cure. Outpatient based pharmacological management represents the main and most important aspect of care, and is usually lifelong. This narrative styled opinion review looks at the pharmacological agents recommended in the guidelines in context of the Northern Territory (NT) of Australia. We explore the concept of validity, a term used to describe the basis of standardising a particular trial or study and the population to which it is applicable. We aim to highlight the problems of the current guidelines based approach. We also present alternatives that could utilise the core principles from major trials, while incorporating regional considerations, which could benefit clients living in the NT and remote Australia., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

The interface between eHealth technologies and disease management in chronic conditions such as chronic heart failure (CHF) has advanced beyond the research domain. The substantial morbidity, mortality, health resource utilization and costs imposed by chronic disease, accompanied by increasing prevalence, complex comorbidities and changing client and health staff demographics, have pushed the boundaries of eHealth to alleviate costs whilst maintaining services. Whilst the intentions are laudable and the technology is appealing, this nonetheless requires careful scrutiny. This review aims to describe this technology and explore the current evidence and measures to enhance its implementation.

Reduced exercise tolerance is an independent predictor of hospital readmission and mortality in patients with heart failure (HF). Exercise training for HF patients is well established as an adjunct therapy, and there is sufficient evidence to support the favorable role of exercise training programs for HF patients over and above the optimal medical therapy. Some of the documented benefits include improved functional capacity, quality of life (QoL), fatigue, and dyspnea. Major trials to assess exercise training in HF have, however, focused on heart failure with reduced ejection fraction (HFREF). At least half of the patients presenting with HF have heart failure with preserved ejection fraction (HFPEF) and experience similar symptoms of exercise intolerance, dyspnea, and early fatigue, and similar mortality risk and rehospitalization rates. The role of exercise training in the management of HFPEF remains less clear. This article provides a brief overview of pathophysiology of reduced exercise tolerance in HFREF and heart failure with preserved ejection fraction (HFPEF), and summarizes the evidence and mechanisms by which exercise training can improve symptoms and HF. Clinical and practical aspects of exercise training prescription are also discussed.

Heart failure with preserved ejection fraction (HFPEF) is common, and at least half of patients presenting with signs and symptoms of heart failure are found to have preserved left ventricular systolic function. They have high mortality and morbidity and exert a substantial impact on health care costs worldwide. A range of conditions has been shown to predispose individuals to development of diastolic dysfunction and HFPEF. Chronic hypertension is the most common cause; it has been suggested that up to 60% of patients with HFPEF are hypertensive. Coronary artery disease, obesity, and diabetes are some of the other common contributory factors. Early detection of asymptomatic patients identified as at risk of developing this syndrome has the potential to reduce the risk of subsequent heart failure; this may be of benefit to focus our attention on prevention and intervention strategies in this population.

Acute exercise improves insulin sensitivity for hours after the exercise is ceased. The skeleton contributes to glucose metabolism and insulin sensitivity via osteocalcin (OC) in its undercarboxylated (ucOC) form in mice. We tested the hypothesis that insulin sensitivity over the hours after exercise is associated with circulating levels of ucOC. Eleven middle-aged (58.1 ± 2.2 years mean ± SEM), obese (body mass index [BMI] = 33.1 ± 1.4 kg/m(2) ) nondiabetic men completed a euglycemic-hyperinsulinemic clamp at rest (rest-control) and at 60 minutes after exercise (4 × 4 minutes of cycling at 95% of HRpeak ). Insulin sensitivity was determined by glucose infusion rate relative to body mass (GIR, mL/kg/min) as well as GIR per unit of insulin (M-value). Blood samples and five muscle biopsies were obtained; two at the resting-control session, one before and one after clamping, and three in the exercise session, at rest, 60 minutes after exercise, and after the clamp. Exercise increased serum ucOC (6.4 ± 2.1%, p = 0.013) but not total OC (p > 0.05). Blood glucose was ∼6% lower and insulin sensitivity was ∼35% higher after exercise compared with control (both p < 0.05). Phosphorylated (P)-AKT (Ak thymoma) was higher after exercise and insulin compared with exercise alone (no insulin) and insulin alone (no exercise, all p < 0.05). In a multiple-linear regression including BMI, age, and aerobic fitness, ucOC was associated with whole-body insulin sensitivity at rest (β = 0.59, p = 0.023) and after exercise (β = 0.66, p = 0.005). Insulin sensitivity, after acute exercise, is associated with circulating levels of ucOC in obese men. Whether ucOC has a direct effect on skeletal muscle insulin sensitivity after exercise is yet to be determined., (© 2014 American Society for Bone and Mineral Research.)

A precise diagnosis of diastolic dysfunction is often difficult and requires invasive techniques to determine left ventricular volume, relaxation, and compliance properties. At this current point of time there is no single non-invasive index available to adequately reflect diastolic function, perhaps because of the numerous factors that can alter diastolic function. In most clinical settings, diastolic function is estimated using Doppler echocardiography. Cardiac magnetic resonance imaging (CMRI) is yet another emerging modality for diastolic function analysis. Here we present a comprehensive review of the various parameters used to assess diastolic function as part of diagnosis of clinical syndrome "Heart failure with preserved ejection fraction (HFPEF)".

Background: Depression is common after a cardiac event, yet there remain few approaches to management that are both effective and scalable., Purpose: We aimed to evaluate the 6-month efficacy and feasibility of a tele-health program (MoodCare) that integrates depression management into a cardiovascular disease risk reduction program for acute coronary syndrome patients with low mood., Methods: A two-arm, parallel, randomized design was used comprising 121 patients admitted to one of six hospitals for acute coronary syndrome., Results: Significant treatment effects were observed for Patient Health Questionnaire 9 (PHQ9) depression (mean difference [change] = -1.8; p = 0.025; effect size: d = 0.36) for the overall sample, when compared with usual medical care. Results were more pronounced effects for those with a history of depression (mean difference [change] = -2.7; p = 0.043; effect size: d = 0.65)., Conclusions: MoodCare was effective for improving depression in acute coronary syndrome patients, producing effect sizes exceeding those of some face-to-face psychotherapeutic interventions and pharmacotherapy. (, Trial Registration Number: ACTRN1260900038623.).

Background: Beta-adrenergic blockade has been shown to improve left ventricular function, reduce hospital admissions and improve survival in chronic heart failure with reduced ejection fraction (HFrEF), with mortality reduction starting early after beta-adrenergic receptor blocker initiation and being dose-related. The aim of this pilot study was to determine the effectiveness of a nurse-led titration clinic in improving the time required for patients to reach optimal doses of the beta-adrenergic receptor blocking agents., Method: We conducted a prospective pilot randomized controlled trial. Twenty eight patients with CHF were randomized to optimisation of beta-adrenergic receptor blocker therapy over six months by either a nurse-led titration (NLT) clinic, led by a nurse specialist with the support of a cardiologist in a CHF clinic, or by their primary care physician (usual care (UC)). The primary endpoint was time to maximal beta-adrenergic receptor blocker dose. The secondary end-point was the proportion of patients reaching the target dose of beta-adrenergic receptor blocker by six months., Results: The patients were predominantly men (72%), age 67 ± 16 years; New York Heart Association (NYHA) functional class I (32%), II (44%) and III (20%); baseline left ventricular ejection fraction 33 ± 10%, and a low mean Charlson co-morbidity score of 2.5 ± 1.4. The time to maximum dose was shorter in the NLT group compared to the UC group (90 ± 14 vs 166 ± 8 days, p < 0.0005). At six months, in the NLT group there were nine patients (82%) on high dose and one patient (9%) on low dose beta-adrenergic receptor blocker compared to the UC group with five (42%) patients reaching maximum dose and five (42%) patients on low dose (p = 0.04). The patients allocated to the NLT group also had significantly less worsening of depression between baseline and six months (p = 0.006)., Conclusion: A NLT clinic improves optimisation of beta-adrenergic receptor blocker therapy through increasing the proportion of patients reaching maximal dose and facilitating rapid up-titration of beta-adrenergic receptor blocker agents in patients with chronic HFrEF., Trial Registration: Australian Clinical Trials Registry (ACTRN012606000383561).

Objectives: Coronary artery disease has been viewed as a relentless, progressive disease. We sought to describe the prevalence and distribution of regression of native vessel disease in coronary artery bypass patients and characterize its relationship with bypass grafting., Methods: Among 619 patients who underwent bypass surgery in a radial artery trial, 405 had follow-up angiography available a mean of 6.2 ± 3.1 years (range, 0-14) after surgery. The percentage of diameter stenosis of each major native coronary vessel was reported by 3 cardiac specialists and classified into grades of nonflow limiting (0%-39%), moderate (40%-69%), flow limiting (70%-80%), severely stenosed (81%-99%), and occluded (100%). Native vessel disease regression was defined as decrease in 1 or more grades of stenosis between the pre- and postoperative angiograms., Results: A total of 1742 native coronary arteries had preoperative stenosis of at least 40% and were included in the present analysis, receiving 753 arterial grafts and 391 saphenous vein grafts. Overall, the prevalence of disease regression was 19.7%, and 45% of patients demonstrated regression in 1 or more vessels. The presence of an arterial graft increased the likelihood of disease regression (21.3% compared with 16% for venous bypassed vessels, P = .012) as did the location in the left circulation (22.6% compared with 13.9% for the right circulation, P < .001) and having a flow-limiting (≥70%) lesion (21.9% compared with 9.8% for moderate lesions, P < .001)., Conclusions: Native coronary artery disease regression after coronary artery bypass grafting is common and affected by conduit type, vessel location, and lesion severity. Surgeons must consider these factors when assessing the requirement for bypass grafts in a borderline lesion., (Copyright © 2014. Published by Mosby, Inc.)

Background and Objectives: B-type natriuretic peptide (BNP) concentration predicts outcome in patients undergoing dialysis. Because survival and cardiovascular risk change across the CKD continuum, serial changes in BNP were compared in patients at different CKD stages and after kidney transplantation., Design, Setting, Participants, & Measurements: Patients with CKD stages 3 and 4 (CKD 3-4), dialysis patients, and kidney transplant recipients (KTRs) from one center had two measurements of BNP taken a median of 161 days apart in 2003-2004 and were followed until July 2012. Both BNP-32 (Triage BNP; Biosite Diagnostics) and NT-BNP-76 (proBNP; Roche Diagnostics) were assayed. The interaction between change in log-transformed BNP concentration over time and patient group was tested by fitting regression models on panel data with random effects. Survival after the second measurement was compared by tertile of change in BNP., Results: Patients with CKD 3-4 (n=48), dialysis patients (n=102), and KTRs (n=73) were followed for a median of 5.7, 4.8, and 5.9 years, respectively. The interaction between patient group and BNP measurements over time was significant for NT-BNP-76 (P<0.001) and BNP-32 (P<0.01). Median NT-BNP-76 increased in dialysis patients and those with CKD 3-4 from 3850 pg/ml (interquartile range [IQR], 1776-12,323 pg/ml) to 18,830 pg/ml (IQR, 6114-61,009 pg/ml; P<0.001) and from 698 pg/ml (IQR, 283-2922 pg/ml) to 2529 pg/ml (IQR, 347-9277 pg/ml; P=0.002), respectively. Change was not significant for KTRs or comparisons made with BNP-32. Survival rate was significantly lower for patients with the highest tertile of change in NT-BNP-76 among patients with CKD 3-4 (P=0.02), but not in the dialysis or KTR groups. In 11 patients who received a kidney transplant during the study, median NT-BNP-76 decreased from 9607 pg/ml (IQR, 2292-31,282 pg/ml) to 457 pg/ml (IQR, 203-863 pg/ml) after transplant (P<0.01)., Conclusions: The temporal trajectory of BNP differs between dialysis patients and those with CKD 3-4 and KTRs. This has important implications for the development of BNP-guided management strategies in CKD., (Copyright © 2014 by the American Society of Nephrology.)

Cardiovascular disease (CVD) and depression are common. Patients with CVD have more depression than the general population. Persons with depression are more likely to eventually develop CVD and also have a higher mortality rate than the general population. Patients with CVD, who are also depressed, have a worse outcome than those patients who are not depressed. There is a graded relationship: the more severe the depression, the higher the subsequent risk of mortality and other cardiovascular events. It is possible that depression is only a marker for more severe CVD which so far cannot be detected using our currently available investigations. However, given the increased prevalence of depression in patients with CVD, a causal relationship with either CVD causing more depression or depression causing more CVD and a worse prognosis for CVD is probable. There are many possible pathogenetic mechanisms that have been described, which are plausible and that might well be important. However, whether or not there is a causal relationship, depression is the main driver of quality of life and requires prevention, detection, and management in its own right. Depression after an acute cardiac event is commonly an adjustment disorder than can improve spontaneously with comprehensive cardiac management. Additional management strategies for depressed cardiac patients include cardiac rehabilitation and exercise programmes, general support, cognitive behavioural therapy, antidepressant medication, combined approaches, and probably disease management programmes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com.)

Introduction: This study will examine the effects of combined aerobic and resistance training on left ventricular remodeling in diabetic patients with diastolic dysfunction. This is the first randomized controlled trial to look for effects of combined strength training and aerobic exercise on myocardial function as well as other clinical, functional, or psychological parameters in diabetic patients with isolated diastolic dysfunction, and will provide important insights into the potential management strategies for heart failure with preserved ejection fraction., Methods and Analysis: This is a prospective, randomized controlled investigator initiated single center trial. Diabetic patients with LV diastolic dysfunction suitable for exercise training intervention will be randomized to three months of a supervised combination of aerobic and strength training exercises, or supervised light stretching (control arm). Pre and post intervention assessment will include stress echocardiography, peak aerobic power with 12-lead ECG, dual-energy X-ray absorptiometry, muscle strength, the capacity to perform activities of daily living (ADLs), and questionnaires to assess self-perceived quality of life and symptoms of depression. The primary endpoint is to compare any change in tissue Doppler-derived LV systolic and early diastolic velocities., Ethics and Dissemination: The current trial protocol has been approved by the Human Research Ethics Committee of Austin Health and the University of Melbourne, Melbourne. The study will be performed in accordance with the Declaration of Helsinki. The investigator, regardless of the outcome, will publish the results of the study., Australian New Zealand Clinical Trials Registry: ACTRN12610000943044.

Heart failure with preserved ejection fraction (HFPEF) is common and represents a major challenge in cardiovascular medicine. Most of the current treatment of HFPEF is based on morbidity benefits and symptom reduction. Various pharmacological interventions available for heart failure with reduced ejection fraction have not been supported by clinical studies for HFPEF. Addressing the specific aetiology and aggressive risk factor modification remain the mainstay in the treatment of HFPEF. We present a brief overview of the currently recommended therapeutic options with available evidence.

Aims: 2D speckle tracking echocardiography allows for assessment of left ventricular (LV) torsional deformation as a composite function of the radial, longitudinal and circumferential fibres. We test the hypothesis that post-exercise LV torsional dynamics are more sensitive markers for myocardial dysfunction than resting measures, and better predictors for exercise capacity compared to post-exercise LV diastolic filling pressure (E/e')., Methods: We studied 88 patients referred for stress echocardiogram. Treadmill exercise was performed using Bruce protocol, and echo images were acquired using GE Vivid 7. LV rotational dynamics were analysed by speckle tracking method using the GE ECHOPAC software. Tertiles were defined according to exercise capacity measured by the achieved metabolic equivalents (METS) adjusted for age and gender. Comparison was made between LV torsional dynamics and E/e' to correlate with METS to predict exercise capacity., Results: Mean age of the study population was 58 years, 48% females. Patients with systolic dysfunction or evidence of ischaemia were excluded from the analysis. No significant correlation was found between METS and LV torsion measures at rest. There was statistically significant correlation between METS and post-exercise LV torsion (r=0.34, p=0.001), twist velocity increase (r=0.27, p=0.01), and incremental change in torsion (r=0.22, p<0.05). In addition, a correlation was also shown between post-exercise E/e' and METS (r=-0.33, p=0.002)., Conclusion: Post-exercise LV torsional dynamics correlate with exercise capacity and may be a useful tool for assessing LV myocardial function in subjects with normal LVEF.

Objectives: We evaluated the influence of lipid exposure upon conduit patency in long-term follow-up after primary CABG., Methods: From a prospectively compiled database, we identified 1207 grafts (436 SV and 771 mixed arterial grafts) among 413 CABG patients with 9.4 ± 2.4 years of follow-up (range 3-13). Surveillance angiography was performed as part of a randomized trial. All available lipid assays were collected from pathology laboratories, and from these, mean annualized lipid exposure was calculated for total cholesterol, HDL, LDL and triglycerides. Angiographical and clinical data were analysed against lipid exposure. Graft failure was defined as occlusion, string sign or >80% stenosis., Results: Six thousand and seventy-seven lipid measurements were obtained, and there were 154 failed grafts. Three hundred and eleven patients received at least one vein graft, and all 413 patients received at least one arterial graft. Overall, only HDL levels were inversely correlated with graft failure, with total cholesterol and LDL showing no associations in a mixed pool of arterial and venous grafts. To assess whether total/LDL cholesterol had no effect or were exerting competing effects in arteries and veins, separate multivariate analyses were performed. Venous graft failure was associated with increased total cholesterol/HDL (P=0.006) and LDL/HDL (P=0.032). By contrast, elevated total cholesterol was correlated with a reduced risk of arterial graft failure (OR for graft failure 0.705, P 0.023) with increasing LDL cholesterol following a similar trend (OR for graft failure 0.729, P=0.051)., Conclusion: Sub-fractions of dyslipidaemia known to be risk factors for native vessel disease appear to similarly influence vein grafts. Arterial conduits are at least more resistant to the effects of high lipid exposure, and appear to be protective. These results favour the use of arterial grafts in patients with poorly controlled dyslipidaemia.