The MindMoves Trial: Cross-Sectional Analyses of Baseline Vascular Risk and Cognition in Older Women with Cardiovascular Disease.

Background: Vascular diseases, including atherosclerotic cardiovascular disease (ASCVD) and stroke, increase the risk of Alzheimer's disease and cognitive impairment. Serum biomarkers, such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1), may be indicators of cognitive health. Objective: We examined whether vascular risk was associated with levels of cognition and serum biomarkers in older women with cardiovascular disease (CVD). Methods: Baseline data from a lifestyle trial in older women (n = 253) with CVD (NCT04556305) were analyzed. Vascular risk scores were calculated for ASCVD (ASCVD risk estimator) and stroke (CHA2DS2-VASc) based on published criteria. Cognition-related serum biomarkers included BDNF, VEGF, and IGF-1. Cognition was based on a battery of neuropsychological tests that assessed episodic memory, semantic memory, working memory, and executive function. A series of separate linear regression models were used to evaluate associations of vascular risk scores with outcomes of cognition and serum biomarkers. All models were adjusted for age, education level, and racial and ethnic background. Results: In separate linear regression models, both ASCVD and CHA2DS2-VASc scores were inversely associated with semantic memory (ß= -0.22, p = 0.007 and ß= -0.15, p = 0.022, respectively), with no significant findings for the other cognitive domains. There were no significant associations between vascular risk scores and serum biomarkers. Conclusions: Future studies should prospectively examine associations between vascular risk and cognition in other populations and additionally consider other serum biomarkers that may be related to vascular risk and cognition.

Cognitive dysfunction prevalence and associated factors in older breast cancer survivors.

OBJECTIVES: The purpose of this study was to examine the prevalence and factors associated with objective and subjective cognitive dysfunction in older breast cancer survivors (BCS). MATERIALS AND METHODS: This cross-sectional descriptive study leveraged previously collected data from older BCS (n = 335). Separate linear regression models were used to determine relationships between demographic factors (age, education), medical factors (comorbidities), disease factors (time since diagnosis, cancer stage), cancer-related symptoms (depressive symptoms, anxiety, fatigue, sleep disturbance) and cognitive dysfunction measures, including objective learning, delayed recall, attention, executive function-working memory, verbal fluency and subjective attentional function. RESULTS: Cognitive dysfunction was prevalent with up to 18.6% of older BCS experiencing mild-moderate dysfunction (1.5 standard deviations below mean of non-cancer controls) in at least one cognitive domain. Poor to moderate subjective attentional function was reported by 26% of older BCS. More depressive symptoms were significantly related to poorer cognitive function including learning (p < .01), delayed recall (p < .05), verbal fluency (p < .001), and subjective attentional function (p < .001) but not attention and executive function-working memory. Age, education, anxiety, and fatigue were also negatively associated with cognitive function in some models (p < .05-0.001). CONCLUSION: Cognitive dysfunction is common among older BCS and depressive symptoms, anxiety, and fatigue are related factors. Importantly, depressive symptoms were not only related to self-report, but also to cognitive performance. Healthcare providers should be aware of and assess for related factors and cognitive dysfunction itself in older BCS even years after diagnosis and treatment thorough geriatric assessment. Future longitudinal research is needed to discern these relationships.

A study protocol for MindMoves: A lifestyle physical activity and cognitive training intervention to prevent cognitive impairment in older women with cardiovascular disease.

INTRODUCTION: Cognitive impairment (CI) and cardiovascular disease (CVD) disproportionately affect women compared to men, and CVD increases risk of CI. Physical activity and cognitive training can improve cognition in older adults and may have additive or synergistic effects. However, no combined intervention has targeted women with CVD or utilized a sustainable lifestyle approach. The purpose of the trial is to evaluate efficacy of MindMoves, a 24-week multimodal physical activity and cognitive training intervention, on cognition and serum biomarkers in older women with CVD. Three serum biomarkers (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor [VEGF], and insulin-like growth factor 1 [IGF-1]) were selected as a priori hypothesized indicators of the effects of physical activity and/or cognitive training on cognition. METHODS: The study design is a randomized controlled trial with a 2 × 2 factorial design, to determine independent and combined efficacies of Mind (tablet-based cognitive training) and Move (lifestyle physical activity with goal-setting and group meetings) on change in cognition (primary outcome) and serum biomarkers (secondary outcomes). We will recruit 254 women aged ≥65 years with CVD and without CI from cardiology clinics. Women will be randomized to one of four conditions: (1) Mind, (2) Move, (3) MindMoves, or (4) usual care. Data will be obtained from participants at baseline, 24, 48, and 72 weeks. DISCUSSION: This study will test efficacy of a lifestyle-focused intervention to prevent or delay cognitive impairment in older women with CVD and may identify relevant serum biomarkers that could be used as early indicators of intervention response.

Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload.

BACKGROUND: In patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments. OBJECTIVES: It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response. METHODS: In a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo. Study entry required hospitalization within the previous 36 h, active dyspnea, and any of the following: 1) estimated glomerular filtration rate <60 ml/min/1.73 m2; 2) hyponatremia; or 3) diuretic resistance (urine output ≤125 ml/h following intravenous furosemide ≥40 mg). The primary endpoint was a 7-point change in self-assessed dyspnea at 8 and 16 h, using a novel standardized approach. RESULTS: We randomized 250 patients. There was no difference in the primary endpoint of day 1 dyspnea reduction, despite significantly greater weight reduction with tolvaptan (-2.4 ± 2.1 kg vs. -0.9 ± 1.8 kg; p < 0.001). At day 3, dyspnea reduction was greater with tolvaptan (p = 0.01). There were 2 significant treatment-by-subgroup interactions: patients without elevated jugular venous pressure and those without ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared with patients with these findings. CONCLUSIONS: Despite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF who were selected for greater potential benefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvement in dyspnea. Apparent subsequent differences in dyspnea warrant further exploration of the temporal relationship between diuresis and dyspnea relief and a possible clinical role for tolvaptan. (Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management [SECRET of CHF]; NCT01584557).

Functional status and quality of life among breast cancer survivors with heart failure: results of the Medicare Health Outcomes Survey.

PURPOSE: The purpose of this population-based study was to examine health-related quality of life (HRQOL) and functional status among breast cancer survivors with heart failure. METHODS: We examined Medicare Health Outcomes Survey data from women aged 65 and older diagnosed with breast cancer in the past 5 years. Surveys were linked to Surveillance, Epidemiology, and End Results cancer registries. Each woman identified with self-reported heart failure (n = 239) was matched to controls without heart failure (n = 685) using propensity scores. The Short Form-36/Veterans Rand-12 measured eight domains of HRQOL. Functional status impairment was measured by limitations in six activities of daily living (ADLs). Linear models estimated associations between heart failure status and HRQOL. Logistic regression models estimated odds ratios for associations between heart failure and ADL impairment. We examined associations for the total study population and subgroups stratified by cancer stage. RESULTS: Among all study participants, heart failure was associated with significant deficits in every HRQOL domain and impairment in all ADLs (p < 0.01, ORs ranged from 1.74 to 2.47). After stratification by cancer stage, heart failure was associated with physical HRQOL deficits across all cancer stages (physical function, vitality, general health) and mental HRQOL deficits only in women with stage I/II cancer (role-emotional, social function). Women with early stage cancer experienced the greatest HRQOL deficits associated with heart failure. CONCLUSIONS: Heart failure in breast cancer survivors is associated with substantial HRQOL deficits and functional status impairment, particularly in early stage cancer. Tailored interventions are needed to improve physical function and mental wellbeing in this high-risk population.

Cardiotoxic heart failure in breast cancer survivors: a concept analysis.

AIM: To report an analysis of the concept of cardiotoxic heart failure in breast cancer survivors. BACKGROUND: Despite numerous studies describing cardiotoxic effects of breast cancer therapies, the literature lacks consistent terminology to describe cancer treatment-induced heart failure, defined by the authors as 'cardiotoxic heart failure'. Breast cancer survivors who develop heart failure may not fit existing conceptual models. A concept analysis of cardiotoxic heart failure in breast cancer survivors is needed to integrate previous research findings and establish the scientific foundation for future intervention research. DESIGN: Concept analysis. DATA SOURCES: An integrative review (1999-2014) was conducted to examine aetiologies and risk factors for heart failure in female breast cancer survivors. Databases searched were CINAHL, Cochrane Library, EmBase, Medline and Scopus. METHODS: Walker and Avant's method for concept analysis includes: select concept; determine purpose; identify uses; define attributes; identify model case; describe borderline, related and contrary cases; identify antecedents/consequences; define empirical referents. RESULTS: In the literature, substantial variation was noted in terminology for breast cancer treatment-induced cardiotoxicity. The authors define cardiotoxic heart failure in breast cancer survivors as chronic heart failure resulting from breast cancer treatment-induced cardiotoxicity among women without pre-existing heart failure diagnosis. No studies were found that described quality of life or tested interventions to preserve quality of life for this population. CONCLUSION: Prospective studies are needed to develop interventions for symptom management to improve quality of life in breast cancer survivors with heart failure. New conceptual paradigms may be needed to improve outcomes for this vulnerable population.

Surgery for Aortic Dilatation in Patients With Bicuspid Aortic Valves: A Statement of Clarification From the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: the "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease" (Circulation. 2010;121:e266-e369) and the "2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease" (Circulation. 2014;129:e521-e643). However, the 2 guidelines differ with regard to the recommended threshold of aortic root or ascending aortic dilatation that would justify surgical intervention in patients with bicuspid aortic valves. The ACC and AHA therefore convened a subcommittee representing members of the 2 guideline writing committees to review the evidence, reach consensus, and draft a statement of clarification for both guidelines. This statement of clarification uses the ACC/AHA revised structure for delineating the Class of Recommendation and Level of Evidence to provide recommendations that replace those contained in Section 9.2.2.1 of the thoracic aortic disease guideline and Section 5.1.3 of the valvular heart disease guideline.

Sensitivity and Specificity of a Five-Minute Cognitive Screening Test in Patients With Heart Failure.

BACKGROUND: Cognitive impairment occurs in up to 80% of patients with heart failure (HF). The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) recommend a 5-minute cognitive screening protocol that has yet to be psychometrically evaluated in HF populations. The aim of this study was to conduct a secondary analysis of the sensitivity and specificity of the NINDS-CSN brief cognitive screening protocol in HF patients. METHODS: The Montreal Cognitive Assessment (MoCA) was administered to 221 HF patients. The NINDS-CSN screen comprises 3 MoCA items, with lower scores indicating poorer cognitive function. Receiver operator characteristic (ROC) curves were constructed, determining the sensitivity, specificity and appropriate cutoff scores of the NINDS-CSN screen. RESULTS: In an HF population aged 76 ± 12 years, 136 (62%) were characterized with cognitive impairment (MoCA <26). Scores on the NINDS-CSN screen ranged from 3-11. The area under the receiver operating characteristic curve indicated good accuracy in screening for cognitive impairment (0.88; P < .01; 95% CI 0.83-0.92). A cutoff score of ≤9 provided 89% sensitivity and 71% specificity. CONCLUSIONS: The NINDS-CSN protocol offers clinicians a feasible telephone method to screen for cognitive impairment in patients with HF. Future studies should include a neuropsychologic battery to more comprehensively examine the diagnostic accuracy of brief cognitive screening protocols.

Depressive symptoms and the relationship of inflammation to physical signs and symptoms in heart failure patients.

BACKGROUND: Depressive symptoms in patients with heart failure can affect the relationship between physical signs and symptoms and inflammation. OBJECTIVE: To examine the relationship between soluble tumor necrosis factor receptor I and physical signs and symptoms and the effects of depressive symptoms on this relationship in patients with heart failure. METHODS: Data on physical signs and symptoms (Symptom Status Questionnaire-Heart Failure), depressive symptoms (Beck Depression Inventory-II), and levels of the receptor (blood samples) were collected from 145 patients with heart failure. Data on the receptor were square root transformed to achieve normality. Patients were divided into 2 groups according to their scores for depressive symptoms (nondepressed <14 and depressed ≥14). Hierarchical multiple regression was used to analyze the data. RESULTS: In the total sample, with controls for covariates, higher levels of the receptor were significantly related to more severe physical signs and symptoms (F = 7.915; P < .001). In subgroup analyses, with controls for covariates, levels of the receptor were significantly related to physical signs and symptoms only in the patients without depression (F = 3.174; P = .005). CONCLUSION: Both depressive symptoms and inflammation should be considered along with physical signs and symptoms in patients with heart failure. Further studies are needed to determine the effects of improvement in inflammation on improvement in physical signs and symptoms, with consideration given to the effects of depressive symptoms.

Depressive symptoms and inflammatory biomarkers in patients with heart failure.

BACKGROUND: Inflammation may be a link between depressive symptoms and outcomes in patients with heart failure. It is not clear whether inflammatory markers are independently related to depressive symptoms in this population. AIM: To determine which inflammatory biomarkers are independently associated with depressive symptoms in heart failure. METHODS AND RESULTS: We analyzed data from 428 outpatients enrolled in a heart failure registry (32% female, 61 ± 12 years, 48% New York Heart Association Class III/IV). Depressive symptoms were measured with the Beck Depression Inventory-II. Serum C-reactive protein (CRP), cytokines (interleukin 1 receptor antagonist, 2, 4, 6, 8, 10), tumor necrosis alpha, and soluble receptors sTNFR1 and sTNFR2 were measured with enzyme immunoassay. Multiple regressions were used to determine which biomarkers were associated with depressive symptoms controlling for demographics, heart failure severity, and clinical variables. Twenty-seven percent (n = 119) had depressive symptoms. CRP was related to depressive symptoms after controlling for age and gender, but no inflammatory biomarkers were associated with depressive symptoms after controlling for all variables in the model. CONCLUSIONS: There was no relationship between inflammatory biomarkers and depressive symptoms. Our findings, in combination with prior researchers', suggest there is not a robust relationship between depressive symptoms and individual biomarkers of inflammation in heart failure.

Generating scientific models of knowledge using arcs.

BACKGROUND: Systematic approaches are needed to review literature on nutrition in heart failure for its scientific merit, relevance, and usefulness and identify directions for future research. OBJECTIVES: To evaluate the feasibility of arcs (J.R.G., Indianapolis, Indiana), a computer program for managing data from literature and modeling knowledge, the objectives were to conduct an integrative review of 10 studies of nutrition in heart failure and generate scientific models of knowledge using arcs. METHODS: A unit of knowledge in arcs is 2 variables linked by a statistical relationship. The computer program arcs categorized variables and relationships found in the 10 explanatory observational studies. It also provided a scientific model for further empirical testing. RESULTS: The computer program arcs aggregated the following: 104 dependent and 93 independent operational variables and 60 associational, 16 predictive, 15 structural, 1 descriptive, and 85 difference relationships. A direct model produced by arcs postulated a structural relationship between cachexia and 18-month mortality, independent of age or New York Heart Association classification, which can be tested as a path theoretical model. CONCLUSION: The computer program arcs appeared to be feasible for conducting an integrative review of nutrition in heart failure. A larger, representative set of literature will enable generation of knowledge and identification of gaps and inconsistencies in findings.