Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study.

BACKGROUND: Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer's disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline. METHODS: The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months. DISCUSSION: The D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12616000546459 ), date registered, 28/04/2016.

Attitudes towards family involvement in nursing care among psychiatric nurses in Hong Kong: A cross-sectional descriptive study.

WHAT IS KNOWN ON THE SUBJECT?: Family-involved interventions can result in better outcomes than traditional mental health care for both service users and their families. Nurses' attitudes towards family involvement can affect family participation in care. Earlier studies on psychiatric nurses' attitudes towards family involvement in care report ambiguous findings. Hong Kong's unique integrated cultures may influence Hong Kong psychiatric nurses' attitudes towards family involvement in nursing care. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The majority of psychiatric nurses had positive views on family involvement in care in Hong Kong. Four variables (i.e. gender, clinical experience, nature of working unit and family nursing training) of psychiatric nurses are associated with their attitudes towards family involvement in care in Hong Kong. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Policy makers should develop strategies to increase psychiatric nurses' awareness of the importance of family involvement in patient care. Nurse educators help to design family nursing training to enhance psychiatric nurses' competence in collaborating with families of people suffering from mental disorders. ABSTRACT: INTRODUCTION: In Hong Kong, involving the family in nursing care is still optional and mainly depends on nurses' attitudes and the willingness of the family. Hong Kong psychiatric nurses' attitudes towards family involvement in nursing care may be influenced by the unique integrated Eastern and Western cultures, however earlier studies report ambiguous findings. AIMS: This study aimed to assess Hong Kong psychiatric registered nurses' attitudes towards family involvement in care and its associated factors. METHODS: This study is a cross-sectional descriptive online survey with convenience sampling based on the Families' Importance in Nursing Care-Nurses' Attitudes (FINC-NA) instrument. RESULTS: Most of the psychiatric nurses had supportive attitudes towards family involvement in care. Females with more clinical experience, working in a rehabilitation-related unit and having attended a family nursing education course were associated with positive attitudes towards family involvement in care. DISCUSSION: The supportive attitude of psychiatric nurses may be explained by the shift of mental health nursing care from hospital care to community care in recent decades. IMPLICATIONS FOR PRACTICE: Mental health nurse education and training in Hong Kong could place more emphasis on building family work skills, particularly for newly qualified nurses and those working in acute inpatient settings.

Can heart rate variability be a bio-index of hope? A pilot study.

Background: Hope can affect the thinking habits, emotional regulations, and behaviors of individuals. Hope is considered as a positive trait by clinicians, who often assess the level of hope in psychological evaluations. Previous measurements of hope were largely based on self-reported questionnaires leading to the problem of subjectivity. Heart Rate Variability (HRV) is a bio index that is an objective, quick, cost effective, and non-invasive measurement. HRV has been used in the evaluation of physical health and some psychiatric conditions. However, it has not been tested for its potential to be a bio-index of the level of hope. Method: This pilot cross-sectional observational study aimed to examine the relationships between HRV and the level of hope among adult Chinese people in Hong Kong. Convenience sampling was used and 97 healthy participants were recruited. Their level of hope was measured by the Dispositional Hope Scale-Chinese (DHS-C), and their HRV was quantified by emWave Pro Plus, a reliable sensor of HRV. Spearman's correlation coefficient analysis was performed on the HRV measurements and DHS-C. Results: The DHS-C's overall mean score was 45.49. The mean scores of the subscale DHS-C (Agency) was 22.46, and the mean scores of DHS-C (Pathway) was 23.03. It was also revealed that there were significant, weak, and negative correlations between the level of hope and four out of ten HRV metrics. One HRV metric was found to have a significant, weak, and positive correlation with the level of hope. Conclusion: This study provided initial evidence to support the use of HRV as a bio-index of hope. Implications of the current study and recommendations for future research directions are discussed.

Beta blocker use in subjects with type 2 diabetes mellitus and systolic heart failure does not worsen glycaemic control.

BACKGROUND: The prognostic benefits of beta-blockers (BB) in patients with systolic heart failure (SHF) are known but despite this, in patients with diabetes they are underutilized. The aim of this study was to assess the effect of beta-blockers (BB) on glycaemic control in patients with Type 2 Diabetes (T2DM) and systolic heart failure (SHF) stratified to beta-1 selective (Bisoprolol) vs. nonselective BB (Carvedilol). METHODS: This observational, cohort study was conducted in patients with T2DM and SHF attending an Australian tertiary teaching hospital's heart failure services. The primary endpoint was glycaemic control measured by glycosylated haemoglobin (HbA1c) at initiation and top dose of BB. Secondary endpoints included microalbuminuria, changes in lipid profile and estimated glomerular filtration rate (eGFR). RESULTS: 125 patients were assessed. Both groups were well matched for gender, NYHA class and use of guideline validated heart failure and diabetic medications. The mean treatment duration was 1.9 ± 1.1 years with carvedilol and 1.4 ± 1.0 years with bisoprolol (p = ns). The carvedilol group achieved a reduction in HbA1c (7.8 ± 0.21% to 7.3 ± 0.17%, p = 0.02) whereas the bisoprolol group showed no change in HbA1c (7.0 ± 0.20% to 6.9 ± 0.23%, p = 0.92). There was no significant difference in the change in HbA1c from baseline to peak BB dose in the carvedilol group compared to the bisoprolol group. There was a similar deterioration in eGFR, but no significant changes in lipid profile or microalbuminuria in both groups (p = ns). CONCLUSION: BB use did not worsen glycaemic control, lipid profile or albuminuria status in subjects with SHF and T2DM. Carvedilol significantly improved glycemic control in subjects with SHF and T2DM and this improvement was non significantly better than that obtained with bisoprolol. BB's should not be withheld from patients with T2DM and SHF.

The CTGF gene -945 G/C polymorphism is not associated with cardiac or kidney complications in subjects with type 2 diabetes.

BACKGROUND: Connective tissue growth factor (CTGF) has been implicated in the cardiac and kidney complications of type 2 diabetes, and the CTGF -945 G/C polymorphism is associated with susceptibility to systemic sclerosis, a disease characterised by tissue fibrosis. This study investigated the association of the CTGF -945 G/C promoter variant with cardiac complications (left ventricular (LV) hypertrophy (LVH), diastolic and systolic dysfunction) and chronic kidney disease (CKD) in type 2 diabetes. METHODS: The CTGF -945 G/C polymorphism (rs6918698) was examined in 495 Caucasian subjects with type 2 diabetes. Cardiac structure and function were assessed by transthoracic echocardiography. Kidney function was assessed using estimated glomerular filtration rate (eGFR) and albuminuria, and CKD defined as the presence of kidney damage (decreased kidney function (eGFR <60 ml/min/1.73 m2) or albuminuria). RESULTS: The mean age ± SD of the cohort was 62 ± 14 years, with a body mass index (BMI) of 31 ± 6 kg/m2 and median diabetes duration of 11 years [25th, 75th interquartile range; 5, 18]. An abnormal echocardiogram was present in 73% of subjects; of these, 8% had LVH alone, 74% had diastolic dysfunction and 18% had systolic ± diastolic dysfunction. CKD was present in 42% of subjects. There were no significant associations between the CTGF -945 G/C polymorphism and echocardiographic parameters of LV mass or cardiac function, or kidney function both before and after adjustment for covariates of age, gender, BMI, blood pressure and hypertension. CTGF -945 genotypes were not associated with the cardiac complications of LVH, diastolic or systolic dysfunction, nor with CKD. CONCLUSIONS: In Caucasians with type 2 diabetes, genetic variation in the CTGF -945 G/C polymorphism is not associated with cardiac or kidney complications.

Preprocedural imaging for patients with atrial fibrillation and heart failure.

Various electrophysiological procedures and device implantation has been shown to improve morbidity and mortality in patients with atrial fibrillation (AF) and patients with heart failure (HF). Noninvasive cardiac imaging is used extensively in the preprocedural patient selection and for procedural guidance. In this review, we will discuss the application of preprocedural cardiac imaging in patients with AF prior to pulmonary vein and left atrial ablation as well as insertion of left atrial occluder device. We also discuss the role of noninvasive cardiac imaging in the selection of appropriate HF patients for device therapy as well as their use in guiding implantation of biventricular pacemaker for cardiac resynchronization therapy by assessing left ventricular ejection fraction, coronary venous anatomy, mechanical dyssynchrony and myocardial scar. We describe new research associated with preprocedural imaging in these patient cohorts.

Validation of rapid automated tissue synchronization imaging for the assessment of cardiac dyssynchrony in sinus and non-sinus rhythm.

AIMS: Cardiac resynchronization therapy is showing benefits for an increasing number of indications but fails to predict response in up to 20-30% of subjects. Echocardiographically assessed dyssynchrony has been proposed as a potential stratifier but current methods are time-consuming and suffer poor reproducibility, thus limiting their clinical utility. This study compared the accuracy, time efficiency, and reproducibility of automated tissue synchronization imaging (Auto TSI) vs. established manual tissue velocity imaging (TVI) techniques for the assessment of intra-ventricular dyssynchrony in sinus and non-sinus rhythm. METHODS AND RESULTS: Fifty consecutive stable systolic heart failure patients on optimal guideline-based medical therapy underwent intra-ventricular dyssynchrony assessment [time to peak velocity (Ts), septal to lateral delay (SLD), and dyssynchrony index (DI)] with TVI and Auto TSI techniques, enabling the assessment of agreement, time efficiency, and reproducibility. Statistical analyses included Pearson's correlation, Bland-Altman's statistics, and coefficient of reproducibility. There was excellent agreement between Auto TSI and TVI for the measurement of Ts [r=0.92, P<0.001, limits of agreement (LOA): -27.3 to 56.5 ms], SLD (r=0.94, P<0.001, LOA: -41 to 49 ms), and DI (r=0.89, P<0.001, LOA: -12.2 to 12.6 ms) which persisted irrespective of cardiac rhythm [Ts: sinus (n=32) r=0.93, P<0.001; non-sinus (n=18) r=0.91, P<0.001]. Automated TSI was more time efficient (3±1 vs. 14±2 min, P<0.001) and demonstrated superior reproducibility: intra-observer (5.5 vs. 9.6%) and inter-observer variability (9.5 vs. 13.4%). CONCLUSION: Automated TSI enables rapid, reproducible intra-ventricular dyssynchrony assessment and overcomes some of the limitations of conventional techniques in sinus and non-sinus rhythm.

Utility of dual-source computed tomography in cardiac resynchronization therapy-DIRECT study.

BACKGROUND: Dual-source computed tomography (CT) can evaluate left ventricular (LV) dyssynchrony, myocardial scar, and coronary venous anatomy in patients undergoing cardiac resynchronization therapy (CRT). OBJECTIVE: We aimed to determine whether dual-source CT predicts clinical CRT outcomes and reduces intraprocedural time. METHODS: In this prospective study, 54 patients scheduled for CRT (mean age 63 ± 11 years; 74% men) underwent preprocedural CT to assess their venous anatomy as well as CT-derived dyssynchrony metrics and myocardial scar. Based on 1:1 randomization, the implanting physician had preimplant knowledge of the venous anatomy in half the patients. In blinded analyses, we measured time to maximal wall thickness and inward wall motion to determine (1) CT global and segmental dyssynchrony and (2) concordance of lead location to regional LV mechanical contraction. End points were 6-month CRT response measured using heart failure clinical composite score and 2-year major adverse cardiac events (MACE). RESULTS: There were 72% CRT responders and 17% with MACE. Two wall motion dyssynchrony indices-global wall motion and opposing anteroseptal-inferolateral wall motion-predicted MACE (P < .01). Lead location concordant to regions of maximal wall thickness was associated with less MACE (P < .01). No CT dyssynchrony metrics predicted 6-month CRT response (P = NS for all). Myocardial scar (43%), posterolateral wall scar (28%), and total scar burden did not predict outcomes (P = NS for all). Preknowledge of coronary venous anatomy by CT did not reduce implant or fluoroscopy time (P = NS for both). CONCLUSION: Two CT dyssynchrony metrics predicted 2-year MACE, and LV lead location concordant to regions of maximal wall thickness was associated with less MACE. Other CT factors had little utility in CRT.

Genetic Variation in Kruppel like Factor 15 Is Associated with Left Ventricular Hypertrophy in Patients with Type 2 Diabetes: Discovery and Replication Cohorts.

Left ventricular (LV) hypertrophy (LVH) is a heritable trait that is common in type 2 diabetes and is associated with the development of heart failure. The transcriptional factor Kruppel like factor 15 (KLF15) is expressed in the heart and acts as a repressor of cardiac hypertrophy in experimental models. This study investigated if KLF15 gene variants were associated with LVH in type 2 diabetes. In stage 1 of a 2-stage approach, patients with type 2 diabetes and no known cardiac disease were prospectively recruited for a transthoracic echocardiographic assessment (Melbourne Diabetes Heart Cohort) (n=318) and genotyping of two KLF15 single nucleotide polymorphisms (SNPs) (rs9838915, rs6796325). In stage 2, the association of KLF15 SNPs with LVH was investigated in the Genetics of Diabetes Audit and Research in Tayside Scotland (Go-DARTS) type 2 diabetes cohort (n=5631). The KLF15 SNP rs9838915 A allele was associated in a dominant manner with LV mass before (P=0.003) and after (P=0.001) adjustment for age, gender, body mass index (BMI) and hypertension, and with adjusted septal (P<0.0001) and posterior (P=0.004) wall thickness. LVH was present in 35% of patients. Over a median follow up of 5.6years, there were 22 (7%) first heart failure hospitalizations. The adjusted risk of heart failure hospitalization was 5.5-fold greater in those with LVH and the rs9838915 A allele compared to those without LVH and the GG genotype (hazard ratio (HR) 5.5 (1.6-18.6), P=0.006). The association of rs9838915 A allele with LVH was replicated in the Go-DARTS cohort. We have identified the KLF15 SNP rs9838915 A allele as a marker of LVH in patients with type 2 diabetes, and replicated these findings in a large independent cohort. Studies are needed to characterize the functional importance of these results, and to determine if the SNP rs9838915 A allele is associated with LVH in other high risk patient cohorts.

Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure.

BACKGROUND: Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. METHODS AND RESULTS: We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2-knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2-knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis-eQTL for LCN2 expression. CONCLUSIONS: Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure.

The Receptor for Advanced Glycation End Products (RAGE) Is Associated with Persistent Atrial Fibrillation.

OBJECTIVE: Upregulation of the receptor for advanced glycation end products (RAGE) has been proposed as a pathophysiological mechanism underlying the development of atrial fibrillation (AF). We sought to investigate if soluble RAGE levels are associated with AF in Caucasian patients. METHODS: Patients (n = 587) were prospectively recruited and serum levels of soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) measured. The patients included 527 with sinus rhythm, 32 with persistent AF (duration >7 days, n = 32) and 28 with paroxysmal AF (duration <7 days, n = 28). RESULTS: Patients with AF were older and had a greater prevalence of heart failure than patients in sinus rhythm. Circulating RAGE levels were higher in patients with persistent AF [median sRAGE 1190 (724-2041) pg/ml and median esRAGE 452 (288-932) pg/ml] compared with paroxysmal AF [sRAGE 799 (583-1033) pg/ml and esRAGE 279 (201-433) pg/ml, p ≤ 0.01] or sinus rhythm [sRAGE 782 (576-1039) pg/ml and esRAGE 289 (192-412) pg/ml, p < 0.001]. In multivariable logistic regression analysis, independent predictors of persistent AF were age, heart failure, sRAGE [odds ratio 1.1 per 100 pg/ml, 95% confidence interval (CI) 1.0-1.1, p = 0.001] and esRAGE [odds ratio 1.3 per 100 pg/ml, 95% CI 1.1-1.4, p < 0.001]. Heart failure and age were the only independent predictors of paroxysmal AF. In AF patients, sRAGE [odds ratio 1.1 per 100 pg/ml, 95% CI 1.1-1.2, p = 0.007] and esRAGE [odds ratio 1.3 per 100 pg/ml, 95% CI 1.0-1.5, p = 0.017] independently predicted persistent compared with paroxysmal AF. CONCLUSIONS: Soluble RAGE is elevated in Caucasian patients with AF, and both sRAGE and esRAGE predict the presence of persistent AF.

Incremental value of cystatin C over conventional renal metrics for predicting clinical response and outcomes in cardiac resynchronization therapy: The BIOCRT study.

BACKGROUND: Despite the benefit of CRT in select patients with heart failure (HF), there remains significant need for predicting those at risk for adverse outcomes for this effective but costly therapy. CysC, an emerging marker of renal function, is predictive of worsening symptoms and mortality in patients with HF. This study assessed the utility of baseline and serial measures of cystatin C (CysC), compared to conventional creatinine-based measures of renal function (estimated glomerular filtration rate, eGFR), in predicting clinical outcomes following cardiac resynchronization therapy (CRT). METHODS: In 133 patients, we measured peripheral venous (PV) and coronary sinus (CS) CysC concentrations and peripheral creatinine levels at the time of CRT implant. Study endpoints included clinical response to CRT at 6 months and major adverse cardiac events (MACE) at 2 years. RESULTS: While all 3 renal metrics were predictive of MACE (all adjusted p ≤ 0.02), only CysC was associated with CRT non-response at 6 months (adjusted odds ratio 3.6, p = 0.02). CysC improved prediction of CRT non-response (p ≤ 0.003) in net reclassification index analysis compared to models utilizing standard renal metrics. Serial CysC > 1mg/L was associated with 6-month CRT non-response and reduced 6-minute walk distance as well as 2-year MACE (all p ≤ 0.04). CONCLUSION: In patients undergoing CRT, CysC demonstrated incremental benefit in the prediction of CRT non-response when compared to standard metrics of renal function. Baseline and serial measures of elevated CysC were predictive of CRT non-response and functional status at 6 months as well as long-term clinical outcomes.

Myocardial scar imaging by standard single-energy and dual-energy late enhancement CT: Comparison with pathology and electroanatomic map in an experimental chronic infarct porcine model.

BACKGROUND: Myocardial scar is a substrate for ventricular tachycardia and sudden cardiac death. Late enhancement CT imaging can detect scar, but it remains unclear whether newer late enhancement dual-energy (LE-DECT) acquisition has benefit over standard single-energy late enhancement (LE-CT). OBJECTIVE: We aim to compare late enhancement CT using newer LE-DECT acquisition and single-energy LE-CT acquisitions with pathology and electroanatomic map (EAM) in an experimental chronic myocardial infarction (MI) porcine study. METHODS: In 8 pigs with chronic myocardial infarction (59 ± 5 kg), we performed dual-source CT, EAM, and pathology. For CT imaging, we performed 3 acquisitions at 10 minutes after contrast administration: LE-CT 80 kV, LE-CT 100 kV, and LE-DECT with 2 postprocessing software settings. RESULTS: Of the sequences, LE-CT 100 kV provided the best contrast-to-noise ratio (all P ≤ .03) and correlation to pathology for scar (ρ = 0.88). LE-DECT overestimated scar (both P = .02), whereas LE-CT images did not (both P = .08). On a segment basis (n = 136), all CT sequences had high specificity (87%-93%) and modest sensitivity (50%-67%), with LE-CT 100 kV having the highest specificity of 93% for scar detection compared to pathology and agreement with EAM (κ = 0.69). CONCLUSIONS: Standard single-energy LE-CT, particularly 100 kV, matched better to pathology and EAM than dual-energy LE-DECT for scar detection. Larger human trials as well as more technical studies that optimize varying different energies with newer hardware and software are warranted.

From gene to protein-experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension.

Hypertension is a major risk factor for stroke, coronary events, heart and renal failure, and the renin-angiotensin system (RAS) plays a major role in its pathogenesis. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II. An "alternate" arm of the RAS now exists in which ACE2 counterbalances the effects of the classic RAS through degradation of Ang II, and generation of the vasodilator Ang 1-7. ACE2 is highly expressed in the heart, blood vessels, and kidney. The catalytically active ectodomain of ACE2 undergoes shedding, resulting in ACE2 in the circulation. The ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats, suggesting that ACE2 may be a candidate gene for hypertension. It is hypothesized that disruption of tissue ACE/ACE2 balance results in changes in blood pressure, with increased ACE2 expression protecting against increased blood pressure, and ACE2 deficiency contributing to hypertension. Experimental hypertension studies have measured ACE2 in either the heart or kidney and/or plasma, and have reported that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, hence increasing ACE2 may be a therapeutic option for the management of high blood pressure in man. There have been relatively few studies of ACE2, either at the gene or the circulating level in patients with hypertension. Plasma ACE2 activity is low in healthy subjects, but elevated in patients with cardiovascular risk factors or cardiovascular disease. Genetic studies have investigated ACE2 gene polymorphisms with either hypertension or blood pressure, and have produced largely inconsistent findings. This review discusses the evidence regarding ACE2 in experimental hypertension models and the association between circulating ACE2 activity and ACE2 polymorphisms with blood pressure and arterial hypertension in man.

Increased arterial inflammation relates to high-risk coronary plaque morphology in HIV-infected patients.

BACKGROUND: Mechanisms predisposing HIV-infected patients to increased cardiovascular disease (CVD) risk remain unclear. OBJECTIVE: To determine the interrelationship between arterial inflammation and high-risk coronary plaque morphology in HIV-infected patients with subclinical coronary atherosclerosis. METHODS: Forty-one HIV-infected patients on stable antiretroviral therapy without known CVD but with atherosclerotic plaque on coronary CT angiography were evaluated with F-FDG-PET. Patients were stratified into 2 groups based on relative degree of arterial inflammation [aortic target-to-background ratio (TBR)]. High-risk coronary atherosclerotic plaque morphology features were compared between groups. RESULTS: HIV-infected patients with higher and lower TBRs were similar with respect to traditional CVD risk parameters. Among HIV-infected patients with higher TBR, an increased percentage of patients demonstrated at least 1 low-attenuation coronary atherosclerotic plaque (40% vs. 10%, P = 0.02) and at least 1 coronary atherosclerotic plaque with both low attenuation and positive remodeling (35% vs. 10%, P = 0.04). Moreover, in the higher TBR group, both the number of low-attenuation plaques per patient (P = 0.02) and the number of vulnerability features in the most vulnerable plaque (P = 0.02) were increased. TBR grouping remained significantly related to the number of low-attenuation plaques/subject (ß = 0.35, P = 0.004), controlling for age, gender, low-density lipoprotein, duration of HIV, and CD4. CONCLUSIONS: These data demonstrate a relationship between arterial inflammation on F-FDG-PET and high-risk coronary atherosclerotic plaque features among HIV-infected patients with subclinical coronary atherosclerosis. Further studies are needed to determine whether arterial inflammation and related high-risk coronary morphology increase the risk of clinical CVD events in the HIV population.

Prevalence, predictors and evolution of echocardiographically defined cardiac abnormalities in adults with type 1 diabetes: an observational cohort study.

AIMS/HYPOTHESIS: The aims of this observational study were to determine the prevalence and predictors of an abnormal echocardiogram in adults with type 1 diabetes, and to assess the evolution of changes in a subset of subjects. METHODS: Cardiac function and structure were prospectively investigated by comprehensive transthoracic echocardiographic techniques in asymptomatic adults with type 1 diabetes seen in the ambulatory care setting. RESULTS: We recruited 136 subjects (mean age 39 years, SD 14 years) with a median diabetes duration of 21 years [25(th), 75(th) interquartile range; 11, 29]. An abnormal echocardiogram was present in 29% of subjects; diastolic dysfunction in 69%, left ventricular hypertrophy in 38% and systolic dysfunction in 10%. The independent predictors of an abnormal echocardiogram were age, with a 9-fold increase in those ≥40 years (OR 9.40 [95% CI 2.68-33.04], P <0.0001), and increased body mass index (BMI), with a 17% increase in risk (P=0.04). A second echocardiogram was available in 65 subjects (3.8±1.7 years later). The results showed that one in five with a normal first study had developed an abnormal second study, mainly diastolic dysfunction, with age being the only independent predictor of progression (P=0.006). CONCLUSIONS/INTERPRETATION: Subclinical echocardiographic abnormalities are common in asymptomatic type 1 diabetes adults, and changes are progressive. The addition of an echocardiogram to complication surveillance programs in those with type 1 diabetes aged ≥40 years may represent a cost-effective way to screen for, and aggressively treat, occult cardiac disease.

HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque.

BACKGROUND: HIV is associated with atherosclerosis and low high-density lipoprotein (HDL). With inflammation, HDL becomes dysfunctional. We previously showed that proinflammatory HDL has high HDL redox activity (HRA). In this study, we compare HRA in HIV-infected versus non-HIV-infected subjects and relate HRA to indices of macrophage activation and cardiovascular disease risk. METHODS: 102 HIV-infected subjects and 41 matched non-HIV controls without clinical cardiovascular disease underwent coronary CT angiography (CTA) and testing for immune/inflammatory biomarkers. The effect of purified HDL from each study subject on the oxidation rate of dihydrorhodamine-123 (DOR) was normalized to the DOR of pooled HDL from healthy subjects. The normalized ratio DOR subject/DOR pooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL. RESULTS: HRA was higher in HIV-infected versus non-HIV subjects (1.4 ±0.01 versus 1.3 ±0.01, P=0.03). In multivariate modelling for HRA among all subjects, HIV status remained positively related to HRA (P=0.02), even after controlling for traditional cardiovascular risk factors, comorbid conditions and immune activation. Among HIV-infected subjects, HRA correlated inversely with HDL (rho=-0.32, P=0.002) and log adiponectin (r=-0.28, P=0.006), and correlated positively with log sCD163 (r=0.24, P=0.02) - a monocyte/macrophage activation marker - and with the percentage of non-calcified coronary atherosclerotic plaque (r=0.29, P=0.03). sCD163 remained significantly associated with HRA in multivariate modelling among HIV-infected subjects (P=0.03). CONCLUSIONS: These data demonstrate increased HRA among HIV-infected subjects versus matched non-HIV subjects with comparable HDL levels. In HIV-infected subjects, HRA relates to macrophage activation and to non-calcified coronary atherosclerotic plaque, which may be rupture-prone. Further studies are needed in HIV-infected patients to elucidate the interplay between immune activation, HDL function and CVD risk. CLINICAL TRIAL REGISTRATION NUMBER: NCT 00455793.

Coronary sinus biomarker sampling compared to peripheral venous blood for predicting outcomes in patients with severe heart failure undergoing cardiac resynchronization therapy: the BIOCRT study.

BACKGROUND: A significant minority of patients receiving cardiac resynchronization therapy (CRT) remain nonresponsive to this intervention. OBJECTIVE: This study aimed to determine whether coronary sinus (CS) or baseline peripheral venous (PV) levels of established and emerging heart failure (HF) biomarkers are predictive of CRT outcomes. METHODS: In 73 patients (aged 68 ± 12 years; 83% men; ejection fraction 27% ± 7%) with CS and PV blood samples drawn simultaneously at the time of CRT device implantation, we measured amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3 (gal-3), and soluble ST2 (sST2) levels. NT-proBNP concentrations >2000 pg/mL, gal-3 concentrations >25.9 ng/mL, and sST2 concentrations >35 ng/mL were considered positive on the basis of established PV cut points for identifying "high-risk" individuals with HF. CRT response was adjudicated by the HF Clinical Composite Score. A major adverse cardiovascular event (MACE) was defined as the composite end point of death, cardiac transplant, left ventricular assist device, and HF hospitalization at 2 years. RESULTS: NT-proBNP concentrations were 20% higher in the CS than in the periphery, while gal-3 and sST2 concentrations were 10% higher in the periphery than in the CS (all P < .001). There were 45% CRT nonresponders at 6 months and 16 (22%) patients with MACE. Triple-positive CS values yielded the highest specificity of 95% for predicting CRT nonresponse. Consistently, CS strategies identified patients at higher risk of developing MACE, with >11-fold adjusted increase for triple-positive CS patients compared to triple-negative patients (all P ≤ .04). PV strategies were not predictive of MACE. CONCLUSION: Our findings suggest that CS sampling of HF biomarkers may be better than PV sampling for predicting CRT outcomes. Larger studies are needed to confirm our findings.

Novel phase-based noise reduction strategy for quantification of left ventricular function and mass assessment by cardiac CT: comparison with cardiac magnetic resonance.

BACKGROUND: Tube current modulation in retrospective ECG gated cardiac computed tomography (CT) results in increased image noise and may reduce the accuracy of left ventricular (LV) ejection fraction (EF) and mass assessment. OBJECTIVE: To examine the effects of a novel CT phase-based noise reduction (NR) algorithm on LV EF and mass quantification as compared to cardiac magnetic resonance (CMR). METHODS: In 40 subjects, we compared the LV EF and mass between CT and CMR. In a subset of 24 subjects with tube current modulated CT, the effect of phase-based noise reduction strategies on contrast-to-noise ratio (CNR) and the assessment of LV EF and mass was compared to CMR. RESULTS: There was excellent correlation between CT and CMR for EF (r=0.94) and mass (r=0.97). As compared to CMR, the limits of agreement improved with increasing strength of NR strategy. There was a systematic underestimation of LV mass by CT compared to CMR with no NR (-10.3±10.1g) and low NR (-10.3±12.5g), but was attenuated with high NR (-0.5±8.3g). Studies without NR had lower CNR compared to low and high NR at both the ES phase and ED phase (all p<0.01). CONCLUSIONS: A high NR strategy on tube current modulated functional cardiac CT improves correlation of EF compared to CMR and reduces variability of EF and mass evaluation by increasing the CNR. In an effort to reduce radiation dose with tube current modulation, this strategy provides better image quality when LV function and mass quantification is needed.