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Background—Heart failure (HF) is a chronic disease that compromises patients’ quality of life (QoL). Interventions designed to reduce distress and improve disease self-management are needed. We evaluated the efficacy of a telephone-based coping skills training (CST) intervention. Methods and Results—This randomized clinical trial involved 180 HF outpatients with reduced ejection fraction. Participants ranged in age from 29 to 87 years (mean=58 years); 27% were women, and 47% were nonwhite. Participants were randomized to either a CST intervention or heart failure education, both delivered over 16 weeks. The primary outcomes were (1) postintervention effects on QoL and HF disease biomarkers (both with α=0.01), and (2) a composite measure of time to death or first hospitalization (with α=0.03) over a median follow-up period of 3 years. CST resulted in greater improvements in QoL compared with heart failure education (P<0.01), including the Kansas City Cardiomyopathy Questionnaire (P=0.009), depressive symptoms (P=0.027), and the 6-minute walk test (P=0.012). However, it did not differentially improve HF disease biomarkers or reduce risk of all-cause hospitalizations or death (hazard ratio=0.84 [95% confidence interval, 0.59–1.12]). Interestingly, exploratory analyses showed that participants randomized to CST experienced a reduction in the composite end point of worsening HF hospitalization or death during the 3-year follow-up period (hazard ratio=0.65 [95% confidence interval, 0.44–0.98]; P=0.040). Conclusions—CST improved QoL in patients with HF. Monitoring and improving QoL is emerging as an important aspect of the clinical management of HF that can reduce disease burden and may help improve clinical outcomes in this vulnerable patient population. [ABSTRACT FROM AUTHOR]

Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction.In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-α receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: χ2=40.6; P<0.0001 and sTNFR-1: χ2=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ2=30.3) and sTNFR-1 (χ2=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ2=6.0; P=0.049) and sTNFR-1 (χ2=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index 0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement.Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers. [ABSTRACT FROM AUTHOR]

The role of the renin-angiotensin system in cognitive impairment is unclear. This work was undertaken to test our hypothesis that renin-angiotensin system may contribute to cognitive decline and brain damage caused by chronic cerebral ischemia. C57BL/6J mice were subjected to bilateral common carotid artery stenosis with microcoil to prepare mice with chronic cerebral hypoperfusion, a model of subcortical vascular dementia. The effects of aliskiren, a direct renin inhibitor, or Tempol, a superoxide scavenger, on brain damage and working memory in these mice were examined. Chronic cerebral hypoperfusion significantly increased brain renin activity and angiotensinogen expression in C57BL/6J mice, which was attributed to the increased renin in activated astrocytes and microvessels and the increased angiotensinogen in activated astrocytes in white matter. Aliskiren pretreatment significantly inhibited brain renin activity and ameliorated brain p67(phox)-related NADPH oxidase activity, oxidative stress, glial activation, white matter lesion, and spatial working memory deficits in C57BL/6J mice with bilateral common carotid artery stenosis. To elucidate the role of oxidative stress in brain protective effects of aliskiren, we also examined the effect of Tempol in the same mice with bilateral common carotid artery stenosis. Tempol pretreatment mimicked the brain protective effects of aliskiren in this mouse model. Posttreatment of mice with aliskiren or Tempol after bilateral common carotid artery stenosis also prevented cognitive decline. In conclusion, chronic cerebral hypoperfusion induced the activation of the brain renin-angiotensin system. Aliskiren ameliorated brain damage and working memory deficits in the model of chronic cerebral ischemia through the attenuation of oxidative stress. Thus, direct renin inhibition seems to be a promising therapeutic strategy for subcortical vascular dementia. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Urgent Need to Measure Effects of Direct Oral Anticoagulants" in the 2016 issue.

[Aim] Metabolic syndrome (MetS) is significantly associated with abnormal blood pressure (BP) circadian rhythms, although the underlying mechanism(s) is unclear. Using SHR/NDmcr-cp (SHRcp), manifesting with hypertension, obesity, insulin resistance and dyslipidemia, we examined the mechanisms underlying abnormal circadian rhythms of BP in MetS.[Methods] (1)We surgically implanted telemetry devices in control SHR and SHRcp to monitor BP continuously. We performed a cross-spectral analysis, using a fast Fourier transformation algorithm, of arterial pulse waves to determine autonomic function and baroreceptor reflex function. Urine samples in dark (active) phase and light (inactive) phase were collected with metabolic cages to measure factors associated with blood pressure control.(2)SHRcp were orally administered azilsartan (1mg/kg/day), an AT1 receptor blocker, once daily at the beginning of the active phase, to examine the effects of azilsartan on the above mentioned parameters.[Results] (1)SHRcp exhibited non-dipper type hypertension, although SHR exhibited dipper-type hypertension. Compared with SHR, SHRcp showed an increased low frequency (LF) power of sBP and a decreased spontaneous baroreceptor reflex gain (sBRG). Thus, SHRcp was characterized by enhanced vascular sympathetic tone and impaired baroreflex function 24 hrs a day. Urine norepinephrine(NE) and aldosterone excretion levels were greater in SHRcp over 24 hrs than in SHR.(2)Azilsartan treatment once daily normalized BP in SHRcp over 24 hrs. Azilsartan had a greater hypotensive effect in SHRcp than in SHR, thus indicating the key role of hypertension in SHRcp. Azilsartan decreased LF of sBP, increased sBRG, and reduced urinary NE excretion levels in SHRcp. Azilsartan also reduced urinary aldosterone excretion over 24 hrs and serum aldosterone concentration, thus increasing urinary sodium excretion in SHRcp.[Conclusion] SHRcp, a model of MetS,exhibit non-dipper type hypertension, and thus they are suitable models for studying abnormal BP circadian rhythms. The mechanism of abnormal BP circadian rhythm in SHRcp was attributed to an impaired autonomic nervous system and aldosterone-induced sodium retention, which were both mediated by AT1 receptor. [ABSTRACT FROM AUTHOR]

This study aimed to explore the clinical significance of breast tumor tissue stiffness based on ultrasound elastographic evaluation in clinical breast cancer. Tumor tissue stiffness is mainly regulated by interactions among tumor cells, stromal cells, and extracellular matrix and was recently regarded as a representative feature of tumor microenvironment. Basic research has already revealed that the tumor stiffness can lead to tumor progression; however, little is known about its clinical significance because thus far, no useful modality is available in the clinical setting. We investigated the tumor stiffness by strain elastography in 503 consecutive patients with invasive breast cancer. Correlations between stiffness and clinicopathological factors, including tumor size, lymph node involvement, tumor subtypes, and stromal-related genes' expressions in primary breast tumor, were statistically examined. We identified that clinical tumor stiffness significantly correlated with lymph node involvement and invasive tumor size but not with hormonal receptor expressions, human epidermal growth factor receptor type 2 status, and ki67 labeling index by analyses of both categorical and continuous variables of stiffness. On multivariate analyses, axillary lymph node metastasis was an independent factor that influenced the stiffness of primary breast tumor. In the gene expression analyses, relatively hard tumors had a significantly high gene expression of lysyl oxidase compared with soft tumors. Our study showed a close relationship between primary tumor stiffness by elastographic evaluation and lymph node involvement in clinical breast cancer. Further investigations on tumor-related tissue stiffness are required., Competing Interests: The authors have no conflicts of interest to disclose.