The heart and gut relationship: a systematic review of the evaluation of the microbiome and trimethylamine-N-oxide (TMAO) in heart failure.

There is an expanding body of research on the bidirectional relationship of the human gut microbiome and cardiovascular disease, including heart failure (HF). Researchers are examining the microbiome and gut metabolites, primarily trimethylamine-N-oxide (TMAO), to understand clinically observed outcomes. This systematic review explored the current state of the science on the evaluation and testing of the gut biome in persons with HF. Using electronic search methods of Medline, Embase, CINAHL, and Web of Science, until December 2021, we identified 511 HF biome investigations between 2014 and 2021. Of the 30 studies included in the review, six were 16S rRNA and nineteen TMAO, and three both TMAO and 16S rRNA, and two bacterial cultures. A limited range of study designs were represented, the majority involving single cohorts (n = 10) and comparing individuals with HF to controls (n = 15). Patients with HF had less biodiversity in fecal samples compared to controls. TMAO is associated with age, BNP, eGFR, HF severity, and poor outcomes including hospitalizations and mortality. Inconsistent across studies was the ability of TMAO to predict HF development, the independent prognostic value of TMAO when controlling for renal indices, and the relationship of TMAO to LVEF and CRP. Gut microbiome dysbiosis is associated with HF diagnosis, disease severity, and prognostication related to hospitalizations and mortality. Gut microbiome research in patients with HF is developing. Further longitudinal and multi-centered studies are required to inform interventions to promote clinical decision-making and improved patient outcomes.

The Contribution of Thoracic Radiation Dose Volumes to Subsequent Development of Cardiovascular Disease in Cancer Survivors.

BACKGROUND: Although radiation therapy (RT) has been recognized for contributing to cardiovascular disease (CVD), it is unknown whether specific doses received by cardiovascular tissues influence development. OBJECTIVE: In this pilot study, we examined the contribution of RT dose distribution on the development of CVD events in patients with cancer within 5 years of RT. METHODS: A retrospective case-controlled design was used matching 28 cases receiving thoracic RT who subsequently developed an adverse CVD event with 28 controls based upon age, gender, and cancer type. Dose volume histograms of nongated computed tomography scans received during RT characterized the dose delivered to the heart. Heart chambers were segmented using an atlas approach, and radiomics features for the segmentation as well as planning dose in each chamber were tabulated for analysis. RESULT: No significant differences were observed in the RT dose statistics between groups, preexisting CVD, nor significant differences of RT doses delivered to distinct chambers of the heart. Cases were found to have greater CVD risk factors at the time of cancer diagnosis. Morphological significant differences for perimeter on border ( P = .043), equivalent spherical radius ( P = .050), and elongation ( P = .038) were observed, with preexisting CVD having the highest values (ie, larger hearts). CONCLUSION: Traditional CVD risk factors were more prevalent in the cases who developed CVD. No differences were observed in doses of RT. Of note, we observed significant differences in heart morphology and mass in known diseased hearts on the pretreatment scans. These new metrics may have implications for the measurement and quantification of CVD.

Subclinical Cardiovascular Disease in Lymphoma Survivors by Sex.

OBJECTIVE: To describe the prevalence of cardiovascular disease in lymphoma survivors by sex. DESIGN: Cross-sectional, correlation. SETTING: Large cancer institute in Southeastern United States. PARTICIPANTS: Participants (N = 31) had a mean age ± standard deviation of 47.6 ± 11.4 years; 55% were male and 84% were White. Participants averaged 5 years since lymphoma treatment. METHODS: During one research visit, routine laboratory tests and fasting lipid levels, coronary artery calcification computed tomography, echocardiography, comprehensive questionnaires, survivorship clinic, and cardiology consultation were measured. Analysis consisted of nonparametric Mann Whitney, t, chi-square, and Fisher's exact tests. MAIN OUTCOMES MEASURES: Comparison of the presence of subclinical cardiovascular disease, calculated cardiovascular disease risk, cardiovascular health knowledge, lifestyle behaviors, symptomatology, and health related quality of life between men and women. RESULTS: Subclinical disease and/or significant cardiovascular disease risk were found in 42%. Women tended to be slightly older (p = .07), had slightly lower but nonsignificant 10-year calculated risk, and slightly higher vascular age. Subclinical disease was detected in 35% of our sample; 28.6% of the women had diastolic dysfunction. Women scored less than men in health-related quality of life based on results of the Short Form Health Survey Physical Functioning (p = .03) and the EQ-5D Index (p = .04). Women had more symptoms (bloating and diarrhea; p < .05). Those with subclinical disease reported other pain (p < .01), numbness in hands or feet (p < .05), and shortness of breath (p < .05). CONCLUSION: Compared with men, more women than expected had subclinical disease, specifically diastolic dysfunction; less reported functioning and health-related quality of life, and greater symptoms. Of clinical relevance is the need for assessment of symptoms that could herald subclinical disease with timely referral.

Single subject design: Use of time series analyses in a small cohort to understand adherence with a prescribed fluid restriction.

PURPOSE: This paper presents a secondary in-depth analysis of five persons with heart failure randomized to receive an education and behavioral intervention on fluid restriction as part of a larger study. METHODS: Using a single subject analysis design, time series analyses models were constructed for each of the five patients for a period of 180 days to determine correlations between daily measures of patient reported fluid intake, thoracic impedance, and weights, and relationships between patient reported outcomes of symptom burden and health related quality of life over time. RESULTS: Negative relationships were observed between fluid intake and thoracic impedance, and between impedance and weight, while positive correlations were observed between daily fluid intake and weight. CONCLUSIONS: By constructing time series analyses of daily measures of fluid congestion, trends and patterns of fluid congestion emerged which could be used to guide individualized patient care or future research endeavors. Employment of such a specialized analysis technique allows for the elucidation of clinically relevant findings potentially disguised when only evaluating aggregate outcomes of larger studies.

An economic evaluation of a self-care intervention in persons with heart failure and diabetes.

BACKGROUND: Persons with concomitant heart failure (HF) and diabetes mellitus constitute a growing population whose quality of life is encumbered with worse clinical outcomes as well as high health resource use (HRU) and costs. METHODS AND RESULTS: Extensive data on HRU and costs were collected as part of a prospective cost-effectiveness analysis of a self-care intervention to improve outcomes in persons with both HF and diabetes. HRU costs were assigned from a Medicare reimbursement perspective. Patients (n = 134) randomized to the self-care intervention and those receiving usual care/attention control were followed for 6 months, revealing significant differences in the number of hospitalization days and associated costs between groups. The mean number of inpatient days was 3 with bootstrapped bias-corrected (BCa) confidence intervals (CIs) of 1.8-4.4 d for the intervention group and 7.3 d (BCa CI 4.1-10.9 d) in the control group: P = .044. Total direct HRU costs per participant were an estimated $9,065 (BCa CI $6,496-$11,936) in the intervention and $16,712 (BCa CI 8,200-$26,621) in the control group, for a mean difference of -$7,647 (BCa CI -$17,588 to $809; P = .21) in favor of the intervention, including intervention costs estimated to be $130.67 per patient. CONCLUSIONS: The self-care intervention demonstrated dominance in lowering costs without sacrificing quality-adjusted life-years.

Isolating the benefits of fluid restriction in patients with heart failure: A pilot study.

BACKGROUND: Fluid restriction (FR) in persons with heart failure (HF) is often prescribed, yet self-regulation and the troublesome symptom of thirst are difficult for patients to manage. AIMS: The purpose of this pilot study was to test an educational and behavioral intervention (EBI) on adherence with prescribed FR and outcome measures of fluid congestion, symptom distress, and health related quality of life (HRQL). Secondary aims were to describe the relationships between self-reported and objectively measured determinants of fluid status and symptoms, and assess the psychometric properties of piloted instruments, and intervention effect sizes. METHODS: NYHA Class II-IV (n=25, 44-83 years, 56% male, 20% minority, mean EF 23.0+11.7%) participants were randomized to the EBI or attention control (AC) and evaluated at baseline, 3 and 6 months. RESULTS: EBI patients trended toward decreasing fluid ingestion (p=0.08), experienced less HF symptom frequency (p=0.13) and severity (p=0.06), and increased symptoms of thirst (p<0.01) across time. Whereas HRQL remained stable in the EBI group, it improved in the AC group over time (p=0.01). There were no significant differences in clinical measures of fluid congestion between groups. CONCLUSIONS: These outcomes suggest that patients receiving the EBI drank slightly less fluid, experienced less typical HF symptoms, greater thirst distress and stable HRQOL. Moderate to large effect sizes for the measures used were observed, and outcomes suggest that a randomized trial of various levels of FR would not potentiate fluid congestion but should specifically address preservation of HRQOL and thirst symptoms.

Recommended patient-reported core set of symptoms to measure in adult cancer treatment trials.

BACKGROUND: The National Cancer Institute's Symptom Management and Health-Related Quality of Life Steering Committee held a clinical trials planning meeting (September 2011) to identify a core symptom set to be assessed across oncology trials for the purposes of better understanding treatment efficacy and toxicity and to facilitate cross-study comparisons. We report the results of an evidence-synthesis and consensus-building effort that culminated in recommendations for core symptoms to be measured in adult cancer clinical trials that include a patient-reported outcome (PRO). METHODS: We used a data-driven, consensus-building process. A panel of experts, including patient representatives, conducted a systematic review of the literature (2001-2011) and analyzed six large datasets. Results were reviewed at a multistakeholder meeting, and a final set was derived emphasizing symptom prevalence across diverse cancer populations, impact on health outcomes and quality of life, and attribution to either disease or anticancer treatment. RESULTS: We recommend that a core set of 12 symptoms--specifically fatigue, insomnia, pain, anorexia (appetite loss), dyspnea, cognitive problems, anxiety (includes worry), nausea, depression (includes sadness), sensory neuropathy, constipation, and diarrhea--be considered for inclusion in clinical trials where a PRO is measured. Inclusion of symptoms and other patient-reported endpoints should be well justified, hypothesis driven, and meaningful to patients. CONCLUSIONS: This core set will promote consistent assessment of common and clinically relevant disease- and treatment-related symptoms across cancer trials. As such, it provides a foundation to support data harmonization and continued efforts to enhance measurement of patient-centered outcomes in cancer clinical trials and observational studies.

A literature synthesis of symptom prevalence and severity in persons receiving active cancer treatment.

PURPOSE: Patients with cancer experience acute and chronic symptoms caused by their underlying disease or by the treatment. While numerous studies have examined the impact of various treatments on symptoms experienced by cancer patients, there are inconsistencies regarding the symptoms measured and reported in treatment trials. This article presents a systematic review of the research literature of the prevalence and severity of symptoms in patients undergoing cancer treatment. METHODS: A systematic search for studies of persons receiving active cancer treatment was performed with the search terms of "multiple symptoms" and "cancer" for studies involving patients over the age of 18 years and published in English during the years 2001 to 2011. Search outputs were reviewed independently by seven authors, resulting in the synthesis of 21 studies meeting criteria for generation of an Evidence Table reporting symptom prevalence and severity ratings. RESULTS: Data were extracted from 21 multi-national studies to develop a pooled sample of 4,067 cancer patients in whom the prevalence and severity of individual symptoms was reported. In total, the pooled sample across the 21 studies was comprised of 62% female, with a mean age of 58 years (range 18 to 97 years). A majority (62%) of these studies assessed symptoms in homogeneous samples with respect to tumor site (predominantly breast and lung cancer), while 38% of the included studies utilized samples with mixed diagnoses and treatment regimens. Eighteen instruments and structured interviews were including those measuring single symptoms, multi-symptom inventories, and single symptom items drawn from HRQOL or health status measures. The MD Anderson Symptom Inventory was the most commonly used instrument in the studies analyzed (n = 9 studies; 43%), while the Functional Assessment of Cancer Therapy, Hospital Anxiety and Depression Subscale, Medical Outcomes Survey Short Form-36, and Symptom Distress Scale were each employed in two studies. Forty-seven symptoms were identified across the 21 studies which were then categorized into 17 logical groupings. Symptom prevalence and severity were calculated across the entire cohort and also based upon sample sizes in which the symptoms were measured providing the ability to rank symptoms. CONCLUSIONS: Symptoms are prevalent and severe among patients with cancer. Therefore, any clinical study seeking to evaluate the impact of treatment on patients should consider including measurement of symptoms. This study demonstrates that a discrete set of symptoms is common across cancer types. This set may serve as the basis for defining a "core" set of symptoms to be recommended for elicitation across cancer clinical trials, particularly among patients with advanced disease.

Educational needs for improving self-care in heart failure patients with diabetes.

PURPOSE: To explore the need for self-monitoring and self-care education in heart failure patients with diabetes (HF- DM patients) by describing cognitive and affective factors to provide guidance in developing effective self-management education. METHODS: A cross-sectional correlation design was employed using baseline patient data from a study testing a 12-week patient and family dyad intervention to improve dietary and medication-taking self-management behaviors in HF patients. Data from 116 participants recruited from metropolitan Atlanta area were used. Demographic and comorbidities, physical function, psychological distress, relationship with health care provider, self-efficacy (medication taking and low sodium diet), and behavioral outcomes (medications, dietary habits) were assessed. Descriptive statistics and a series of chi-square tests, t tests, or Mann-Whitney tests were performed to compare HF patients with and without DM. RESULTS: HF-DM patients were older and heavier, had more comorbidities, and took more daily medications than HF patients. High self-efficacy on medication and low-sodium diet was reported in both groups with no significant difference. Although HF-DM patients took more daily medications than HF, both groups exhibited high HF medication-taking behaviors. The HF-DM patients consumed significantly lower total sugar than HF patients but clinically higher levels of sodium. CONCLUSIONS: Diabetes educators need to be aware of potential conflicts of treatment regimens to manage 2 chronic diseases. Special and integrated diabetes self-management education programs that incorporate principles of HF self-management should be developed to improve self-management behavior in HF-DM patients.

Development, psychometric testing, and revision of the Atlanta Heart Failure Knowledge Test.

BACKGROUND AND RESEARCH OBJECTIVE: Several heart failure (HF) knowledge tools have been developed and tested over the past decade; however, they vary in content, format, psychometric properties, and availability. This article details the development, psychometric testing, and revision of the Atlanta Heart Failure Knowledge Test (A-HFKT) as a standardized instrument for both the research and clinical settings. PARTICIPANTS AND METHODS: Development and psychometric testing of the A-HFKT were undertaken with 116 New York Heart Association (NYHA) class II and III community-dwelling HF patients and their family members (FMs) participating in a family intervention study. Internal consistency, reliability, and content validity were examined. Construct validity was assessed by correlating education level, literacy, dietary sodium ingestion, medication adherence, and healthcare utilization with knowledge. RESULTS: Content validity ratings on relevance and clarity ranged from 0.55 to 1.0, with 81% of the items rated from 0.88 to 1.0. Cronbach alpha values were .84 for patients, .75 for FMs, and .73 for combined results. Construct validity testing revealed a small but significant correlation between higher patient and FM knowledge on sodium restriction questions and lower ingested sodium, r = -0.17, P = .05 and r = -0.19, P = .04, respectively, and between patient knowledge and number of days that medications were taken correctly (diuretics: r = 0.173, P < .05, and angiotensin-converting enzyme: r = 0.223, P = .01). Finally, patients seeking emergency care or requiring hospitalization in the 4 months before study entry were found to have significantly lower FM knowledge using both t test and logistic regression modeling. CONCLUSIONS: The A-HFKT was revised using the content and construct validity data and is available for use with HF patients and FMs. The construct validity testing indicates that patient knowledge has a significant relationship to aspects of self-care. Furthermore, family knowledge may influence patient adherence with sodium restriction and healthcare utilization behavior.