Globally, there are almost 26 million adults who are living with heart failure.1 Heart failure is one of the most common causes of hospitalization, hospital readmission, and death.2,3 Moreover, the economic burden of heart failure care is tremendous, with 1% to 2% of all health care expenditure in Europe and North America attributed to heart failure.4 Much of these costs are driven by unscheduled hospitalization,4,5 which is linked to poor heart failure self-care.6
Self-care is defined as an active decision-making process aimed to maintain health through treatment and advice adherence, recognition and timely management of symptoms, implementation of changes in the event of worsening symptoms, and evaluation of correct health behaviors.7,8 Because of the long-term nature and complexity of heart failure treatment regimens and the importance of intervention in the early stages of decompensation, chronic heart failure self-care requires patients to actively engage with clinicians, follow medical regimens, adhere to diet and exercise recommendations, and modify medications and health behaviors according to symptoms.8 Poor self-care is associated with high readmission rates within 30 days of discharge9 and increased mortality in heart failure.10 Thus, good self-care in heart failure is crucial in avoiding hospitalizations and improving survival.11 However, as many as two-thirds of patients with heart failure have inadequate self-care.12,13
Effective self-care requires cognitive competency/executive decision-making abilities, and cognitive impairment is associated with poor self-care.14–16 Particularly, executive decision-making abilities are necessary for cognitive control of behavior and successful monitoring of behaviors that facilitate the attainment of chosen goals.17,18 However, executive decision-making impairment is common in heart failure, with the incidence of inadequate executive decision-making ranging from 25% to 80% in adults with heart failure.16,19 Executive decision-making depends on brain structural integrity,20 and various brain sites are involved in executive function,21 including the prefrontal cortices.21,22 However, brain structural status in executive decision-making control regions (prefrontal cortices) and their relationships to self-care in heart failure have not been reported. Therefore, the specific aim of this study was to examine the relationships between heart failure self-care and brain tissue integrity of the prefrontal cortices using non-invasive brain magnetic resonance imaging (MRI)–based diffusion tensor imaging (DTI) procedures.
Study Design and Sample
A correlational research design was used for this study. Subjects with heart failure were recruited from the Ahmanson-University of California Los Angeles Cardiomyopathy Center via study flyers and postings. A total of 21 hemodynamically optimized23 subjects with heart failure were studied (age, 53.8 ± 7.9 years; 15 men; body mass index, 26.9 ± 5.0 kg/m2; left ventricular ejection fraction, 25.1% ± 6.1%; New York Heart Association [NYHA] functional class II/III). All subjects with heart failure were diagnosed based on national heart failure diagnostic criteria,24 had dilated systolic cardiomyopathy with reduced left ventricular ejection fraction (<0.35), and were classified as NYHA functional class II or III. Patients with NYHA IV were excluded for safety reasons, because these patients with heart failure cannot lay supine in the MRI scanner for the required MRI scanning period (approximately 1 hour). Additional exclusion criteria included claustrophobia, loose/nonremovable metal (such as braces, embolic coils, pacemakers/implantable cardioverter-defibrillators and stents), and weight more than 125 kg (scanner table limitations). All subjects had no history of stroke or carotid vascular disease and were treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and diuretics to maintain stable body weight for at least 6 months before study data collection. We performed brain MRI on subjects within 1 year of heart failure diagnosis to minimize variability in measures from disease onset. All subjects gave written informed consent before the study, and the study protocol was approved by the institutional review board of the University of California Los Angeles.
Data Collection Measures
Demographic, Biophysical, and Clinical Data
Demographic data were obtained from each subject via direct measurement (including height and weight) by the investigative team. Clinical data (eg, left ventricular ejection fraction) were gathered from patients' medical records.
The Montreal Cognitive Assessment (MoCA) test was used to screen cognition, including attention and concentration, executive functions, memory, language, visuo-constructional skills, conceptual thinking, calculations, and orientation. The test takes approximately 10 minutes to complete. The total possible score is 30 points, and a score of 26 or higher is considered normal and lower than 26 is associated with cognitive impairment.25
Executive function was measured by the Trail Making Test (TMT) B, which is based on timed trails and is a classic test for evaluation of executive function. This test is also used to assess visual search, mental flexibility, scanning, and speed of processing.26 The TMT B consists of 12 circled numbers and letters (A–L) spread randomly on a page, and these representations must be connected sequentially (ie, 1, A, 2, B, 3, C, etc). The score is based on time (in seconds) taken for completion of the task.
Measurement of Self-care
Self-care was measured with the Self-care of Heart Failure Inventory (SCHFI; version 6) questionnaire. The SCHFI is an ordinal, self-administered instrument that measures subjects' opinions of their ability to care for their heart failure diagnosis. It yields a performance rating score and has 3 subscales: self-care maintenance (10 items), self-care management (6 items), and self-care confidence (6 items). The validity of this instrument was established by the developers via concurrent and construct validity and reliability α reported from .553 (maintenance scale) to .827 (confidence scale)8 and is best represented by self-care maintenance and self-care management.8 Adequate self-care is indicated by a score 70 or higher on each of the subscales,8 and the instrument has been shown to be sensitive in heart failure to changes in self-care.8
Magnetic Resonance Imaging
Brain imaging studies were performed using a 3.0-Tesla MRI scanner (Siemens, Prisma, Erlangen, Germany). Foam pads were placed on both sides of the head to minimize head motion–related artifacts. High-resolution T1-weighted images were acquired using a magnetization-prepared rapid-acquisition gradient-echo pulse sequence (repetition time, 2200 milliseconds; echo time, 2.4 milliseconds; inversion time, 900 milliseconds; flip angle, 9°; matrix size, 320 × 320; field of view, 230 × 230 mm; slice thickness, 0.9 mm). Proton density and T2-weighted images were collected simultaneously in the axial plane by using a dual-echo turbo spin-echo pulse sequence (repetition time, 10 000 milliseconds; echo time, 12 124 milliseconds; flip angle, 130°; matrix size, 256 × 256; field of view, 230 × 230 mm; slice thickness, 3.5 mm). Diffusion tensor imaging was performed using a single-shot echo-planar imaging with twice-refocused spin-echo pulse sequence (repetition time, 12 200 milliseconds; echo time, 87 milliseconds; flip angle, 90°; bandwidth, 1345 Hz/pixel; matrix size, 128 × 128; field of view, 230 × 230 mm; slice thickness, 1.7 mm; no interslice gap; diffusion values, 0 and 800 s/mm2; diffusion gradient directions, 32; series, 2).
Magnetic Resonance Imaging Data Processing and Analysis
The statistical parametric mapping package SPM12 (http://www.fil.ion.ucl.ac.uk/spm/), DTI-Toolkit (v0.6.4.1),27 MRIcroN,28 and MATLAB-based (http://www.mathworks.com/) custom software were used for evaluation of images, data processing, and analyses. High-resolution T1-, proton density–, and T2-weighted images were evaluated for any visible brain pathology, including tumors, cysts, or any other mass lesions. Diffusion- and non-diffusion-weighted images were examined for head motion–related or other artifacts before mean diffusivity (MD) quantification. No subjects showed major visible brain tissue changes or head-motion or other imaging artifacts.
Calculation of Mean Diffusivity Maps
Mean diffusivity is an index, derived from DTI data, and identifies various types of pathologic changes (eg, vasogenic edema, cytotoxic edema, and cellular and axonal loss). Mean diffusivity procedures measure tissue integrity, and values are brain site specific and dependent on age. Because cortical sites are large and normal values change area to area within prefrontal cortices, there are no universally set MD value ranges for prefrontal cortices that indicate minimal versus severe injury. Higher MD values indicate tissue injury/cellular loss.29 Mean diffusivity maps were obtained from 2 separate series of DTI series, as described earlier,29 and subsequently realigned and averaged to obtain good ratio of signal to background noise (signal outside the brain parenchyma is called background noise). Mean diffusivity maps were normalized to a common space and smoothed. Because all subjects with heart failure have different head sizes and orientations during the MRI data collection, calculated MD maps were wrapped to a common space to remove variations in head sizes and orientations before region-by-region correlations across all subjects.
Demographics and Other Variables
The SPSS v 24 (IBM, Armonk, New York) software was used for descriptive statistics to examine demographic, biophysical, physiological, cognitive, and SCHFI variables. A value of P < .05 was chosen to establish statistical significance for all statistical tests.
Relationships between Regional Mean Diffusivity Values and Self-care of Heart Failure Index and Trail Making Test B Scores
The smoothed MD maps were correlated voxel by voxel with SCHFI (maintenance, management, and confidence scales) and TMT B scores in subjects with heart failure using partial correlation procedures (SPM12; covariates, age, and gender; uncorrected threshold, P < .005), and analysis was limited to prefrontal cortex areas. Brain clusters with significant correlations with SCHFI and TMT B scores were overlaid onto T1-weighted images for structural identification. Brain clusters appearing in the prefrontal cortices were extracted from all the subjects and correlated with SCHFI and TMT B scores using partial correlation procedures to examine correlation effect sizes (SPSS; covariates, age, and gender; P < .05).
Demographic and Clinical Variables
Demographic, biophysical, and clinical variables are summarized in Table 1. More than half of the sample (57.1%) had cognitive deficits (total MoCA scores <26) and 52.4% of patients with heart failure performed below average in TMT B (a score >74.55 seconds was considered abnormal).26 The mean ± SD global MoCA and TMT B scores of this sample were 24.5 ± 3.8 and 90.2 ± 73.3 (seconds), respectively. In each SCHFI subscale, more than 40% of subjects with heart failure showed inadequate self-care (SCHFI scores <70) (maintenance, 42.9%; management, 45.5%; and confidence, 42.9%). The mean ± SD SCHFI maintenance score was 70.78 ± 11.37; management, 70 ± 17.32 (for 11 subjects with symptoms); and confidence, 74.91 ± 15.76.
Correlations Between Mean Diffusivity Values and Self-care of Heart Failure Index and Trail Making Test B Scores
The mean ± SD MD values of left and right prefrontal cortices were 1.46 ± 0.16 (×10−3 mm2/s) and 1.44 ± 0.14 (×10−3 mm2/s), respectively, and showed significant negative correlations with SCHFI maintenance (left prefrontal, r = −0.64, P = .003; right prefrontal, r = −0.70, P = .001) and SCHFI management scores (left prefrontal, r = −0.93, P < .001; right prefrontal, r = −0.86, P = .003). Correlation was not significant between prefrontal MD values and SCHFI confidence scores (Table 2; Figures 1–3). Significant positive correlations also appeared between MD values and TMT B scores (left prefrontal, r = 0.71, P = .001; right prefrontal, r = 0.74, P < .001). Correlation between TMT B scores and SCHFI subscale scores were not significant (TMT B vs SCHFI maintenance, r = −0.18, P = .44; SCHFI confidence, r = 0.07, P = .76; management [n = 11], r = −0.18, P = .59).
This study showed strong relationships between heart failure self-care scores and brain tissue integrity in prefrontal cortices, sites that control key cognitive functions including executive functions such as memory, problem solving, and decision-making that are necessary for day-to-day heart failure self-care. Compromised brain structural changes in prefrontal cortices have been shown in patients with heart failure,21,22 and our findings report hindered self-care abilities in this condition. Interestingly, self-care confidence scores were not significantly correlated to prefrontal tissue integrity, suggesting that this domain may not be affected by injury in these sites or influenced by executive decision-making abilities. Although self-efficacy, defined as subject's confidence to achieve a desired outcome,30 has been shown to be independently associated with total brain and total gray matter volumes,31 specific brain regions linked to self-care confidence still need to be identified.
Current methods of improving self-care in heart failure focus on patients' education in which patients are taught to monitor their condition and to recognize when to seek medical assistance.11 Various education modalities have been used in an effort to improve self-care in patients with heart failure, including verbal instructions and/or brochures, communications software, tele-homecare programs, and others, yet often with no significant improvement on self-care over usual home care.32 Limited effects of these self-care education approaches may be a result of the lack of recognition and consideration of brain injury in cognitive control sites and failure to address brain changes in patients with heart failure. Although up to 80% of patients with subjects with heart failure show cognitive/executive decision-making deficits,16,19 patients are often assumed to have intact cognition and self-care abilities needed to process complex heart failure self-care information, make self-care decisions based on the information, and take appropriate actions/behaviors as directed by healthcare providers. As a result, patients' poor adherence has been considered the primary reason for lack of improvement after self-care education. In fact, it is more likely that information given during the patient education sessions may not have been processed or retained because of brain injury. Many patients with heart failure in this study showed deficits in cognition/executive decision-making, which was associated with brain tissue injury in prefrontal cortices. Decision-making ability (eg, deciding what to do from multiple options) and ability to apply self-care education contents to plan complex cognitive behaviors, such as heart failure symptom management and maintenance, may be compromised because of brain tissue damage in prefrontal cortices, and therefore, even if instructed, patients are unable to perform these self-care tasks (eg, monitoring and reporting symptom changes), as directed by clinicians.
Clinical implication of current study findings is consideration of brain injury in cognition/executive function regulatory sites to improve heart failure self-care (eg, neuroprotection and repair). Although mechanisms for brain injury in heart failure are multifactorial,33 compromised cerebral blood flow secondary to reduced/low cardiac output in patients with heart failure is considered to be a main contributing factor.34 Current approaches to address brain injury focus on improving cardiac performance and systemic hemodynamics which have been shown to have a positive impact on the brain.35 Other therapeutic options shown to be beneficial include angiotensin-converting enzyme inhibitors (angiotensin-converting enzyme resides in major cerebral arteries and the inhibitor medication showed increase in cerebral perfusion),36 exercise programs,37 and memory interventions.38 Although thiamine supplement can be a plausible option, because thiamine deficiency may be an important component of brain injury, conclusive data on the role of thiamine deficiency in brain changes of patients with heart failure are lacking.39 Evidence suggests that treating depression, common in patients with heart failure, may help address elevated neurohormonal and inflammatory activities on the brain and thus reduce damaging impact on brain tissue.33,40 Promoting brain protection and neural regrowth may be a promising approach to reduce brain injury in heart failure, which may eventually improve heart failure self-care.33 However, at present time it is uncertain whether neurogenesis can be induced in the prefrontal cortices or the impact of such neurogenesis on heart failure self-care.
Because it may take time to fully understand the causes and mechanisms of brain injury in heart failure, developing new therapies to treat brain injury (eg, neurogenesis and neuroprotection), establishing causal relationship between brain injury and self-care abilities (whether treating brain injury results in improved self-care), and exploring alternative and innovative ways to improve self-care may need to be considered as well as continuing with current evidence-based recommendations, such as exercise, nutrition, angiotensin-converting enzyme inhibitors, and treating depression. For example, interventions/strategies used in other patient populations with impaired cognition (eg, dementia patients and students with learning disability) could be adapted and used for the education of patients with heart failure to improve self-care. These potential interventions include memory aids, such as prompts, diagrams, and graphics/pictures, and brain training with memory apps for short-term memory deficits.41 Surrogate decision-making (such as family members and friends) and team care may provide support to patients and enhance their self-care abilities. Existing programs (eg, tele-healthcare) can incorporate novel strategies to better accommodate memory dysfunction in patients with heart failure, such as use of music, which has been shown to reduce cognitive decline especially in autobiographical and episodic memories, psychomotor speed, executive function domains, and global cognition and stimulate cognitive function.42–44 In addition, evaluation of cognition and self-care abilities in patients with heart failure in the clinical setting (so far, this has been done mainly in the research setting) should be part of routine practice to allow clinicians to identify those at greater risk of poor self-care and to help tailor self-care education to the patient's cognitive function. In fact, the 2016 European Society of Cardiology Guidelines suggested the use of the Mini-Mental State Examination and MoCA tests for the diagnosis and treatment of heart failure-induced brain injury.45
Although our findings add to the knowledge on relationships between brain tissue integrity of cognitive/executive function control areas and heart failure self-care scores, this study has several limitations. The small sample size limited our ability to consider other important variables in our analyses (such as medications). Another limitation of this study includes sample characteristics (younger age, mostly nonischemic etiology, and relative lack of co-morbidities), which do not reflect the demographics of the majority of patients with heart failure, limiting the generalization of this study's findings. However, by selecting subjects with heart failure who had these atypical characteristics, we could control for variables that can alter brain structures (such as age, brain vessel atherosclerotic-induced neural ischemia, and medical comorbidities) and thus obtain a more homogeneous sample. Consequently, the study findings more likely reflect the contribution of heart failure toward brain injury rather than age, neurovascular atherosclerosis, or other medical conditions. Because this study was cross-sectional with a correlational design, the findings cannot be interpreted as causal relationships.
The present study showed that brain tissue injury specific to cognitive/executive function control sites (prefrontal cortices) is associated with poor perception of heart failure self-care management and maintenance. The findings indicate that consideration of protection and repair of prefrontal cortices may help improve heart failure self-care and potentially improve the outcomes of this high-risk patient population.
What’s New and Important
- Brain tissue integrity in cognitive/executive function regulatory regions is associated with perception of heart failure self-care maintenance and management.
- Protection and repair of brain tissue in executive control areas may improve heart failure self-care.
- Further research is needed to identify causal relationships between brain tissue injury and heart failure self-care and to identify potential interventions.
The authors thank Ms Cristina Cabrera-Mino for assistance with data collection.
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Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved
Heart failure; Self-care; Brain; Magnetic Resonance Imaging