Bowel burdens: a systematic review and meta-analysis examining the relationships between bowel dysfunction and quality of life after spinal cord injury.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: Many individuals with spinal cord injury (SCI) experience autonomic dysfunction, including profound impairments to bowel and cardiovascular function. Neurogenic bowel dysfunction (NBD) is emerging as a potential determinant of quality of life (QoL) after SCI. For individuals with high-level lesions ( > T6), bowel care-related autonomic dysreflexia (B-AD; profound episodic hypertension) further complicates bowel care. We aimed to evaluate the extent of bowel dysfunction after SCI, and the impact of bowel dysfunction on QoL after SCI. METHODS: We searched five databases to identify research assessing the influence of NBD or B-AD on QoL after SCI. Metrics of bowel dysfunction (fecal incontinence [FI], constipation, time to complete, and B-AD) and QoL data were extracted and synthesised. Where possible, meta-analyses were performed. RESULTS: Our search identified 2042 titles, of which 39 met our inclusion criteria. Individuals with SCI identified problems with NBD (74.7%), FI (56.9%), and constipation (54.6%), and 49.3% of individuals with SCI > T6 experienced B-AD. Additionally, 40.3% of individuals experienced prolonged defecation ( > 30 min). Moderate/severe deterioration in QoL due to NBD was reported by 55.5% of individuals with SCI, with negative impacts on physical, emotional, and social health-related QoL associated with inflexibility of bowel routines, fear of accidents, and loss of independence. CONCLUSION: Bowel dysfunction and bowel care challenges are prevalent and disabling for individuals with SCI, with a profoundly negative impact on QoL. Improving bowel management is a key target to improve QoL for those living with SCI.

Associations between spontaneous electroencephalogram oscillations and oxygen saturation across normobaric and hypobaric hypoxia.

High-altitude indoctrination (HAI) trains individuals to recognize symptoms of hypoxia by simulating high-altitude conditions using normobaric (NH) or hypobaric (HH) hypoxia. Previous studies suggest that despite equivalent inspired oxygen levels, physiological differences could exist between these conditions. In particular, differences in neurophysiological responses to these conditions are not clear. Our study aimed to investigate correlations between oxygen saturation (SpO2 ) and neural responses in NH and HH. We recorded 5-min of resting-state eyes-open electroencephalogram (EEG) and SpO2 during control, NH, and HH conditions from 13 participants. We applied a multivariate framework to characterize correlations between SpO2 and EEG measures (spectral power and multiscale entropy [MSE]), within each participant and at the group level. Participants were desaturating during the first 150 s of NH versus steadily desaturated in HH. We considered the entire time interval, first and second half intervals, separately. All the conditions were characterized by statistically significant participant-specific patterns of EEG-SpO2 correlations. However, at the group level, the desaturation period expressed a robust pattern of these correlations across frequencies and brain locations. Specifically, the first 150 s of NH during desaturation differed significantly from the other conditions with negative absolute alpha power-SpO2 correlations and positive MSE-SpO2 correlations. Once steadily desaturated, NH and HH had no significant differences in EEG-SpO2 correlations. Our findings indicate that the desaturating phase of hypoxia is a critical period in HAI courses, which would require developing strategies for mitigating the hypoxic stimulus in a real-world situation.

Pain associated with intravascular instrumentation reduces orthostatic tolerance and predisposes to vasovagal reactions in healthy young adults without needle phobia: a randomised controlled study.

PURPOSE: Vasovagal syncope (VVS), or fainting, is frequently triggered by pain, fear, or emotional distress, especially with blood-injection-injury stimuli. We aimed to examine the impact of intravenous (IV) instrumentation on orthostatic tolerance (OT; fainting susceptibility) in healthy young adults. We hypothesized that pain associated with IV procedures would reduce OT. METHODS: In this randomised, double-blind, placebo-controlled, cross-over study, participants (N = 23; 14 women; age 24.2 ± 4.4 years) underwent head-up tilt with combined lower body negative pressure to presyncope on three separate days: (1) IV cannulation with local anaesthetic cream (EMLA) (IV + EMLA); (2) IV cannulation with placebo cream (IV + Placebo); (3) sham IV cannulation with local anaesthetic cream (Sham + EMLA). Participants rated pain associated with IV procedures on a 1-5 scale. Cardiovascular (finger plethysmography and electrocardiogram; Finometer Pro), and forearm vascular resistance (FVR; brachial Doppler) responses were recorded continuously and non-invasively. RESULTS: Compared to Sham + EMLA (27.8 ± 2.4 min), OT was reduced in IV + Placebo (23.0 ± 2.8 min; p = 0.026), but not in IV + EMLA (26.2 ± 2.2 min; p = 0.185). Pain was increased in IV + Placebo (2.8 ± 0.2) compared to IV + EMLA (2.0 ± 2.2; p = 0.002) and Sham + EMLA (1.1 ± 0.1; p < 0.001). Orthostatic heart rate responses were lower in IV + Placebo (84.4 ± 3.1 bpm) than IV + EMLA (87.3 ± 3.1 bpm; p = 0.007) and Sham + EMLA (87.7 ± 3.1 bpm; p = 0.001). Maximal FVR responses were reduced in IV + Placebo (+ 140.7 ± 19.0%) compared to IV + EMLA (+ 221.2 ± 25.9%; p < 0.001) and Sham + EMLA (+ 190.6 ± 17.0%; p = 0.017). CONCLUSIONS: Pain plays a key role in predisposing to VVS following venipuncture, and our data suggest this effect is mediated through reduced capacity to achieve maximal sympathetic activation during orthostatic stress. Topical anaesthetics, such as EMLA, may reduce the frequency and severity of VVS during procedures requiring needles and intravascular instrumentation.

Relationships between cardiovascular disease risk, neuropathic pain, mental health, and autonomic function in chronic spinal cord injury.

STUDY DESIGN: Multicentre, cross-sectional study. OBJECTIVES: To determine if clinical measures of poor mental health (MH-) and neuropathic pain (NP) are related to increased CVD risk in individuals with chronic spinal cord injury (SCI), and further elucidate the relationships between CVD risk, autonomic function, NP, and MH-. SETTING: Eight SCI rehabilitation centres in the Netherlands. METHODS: Individuals (n = 257) with a traumatic, chronic (≥10 yrs) SCI, with age at injury between 18-35 years, completed a self-report questionnaire and a one-day visit to a rehabilitation centre for testing. CVD risk was calculated using Framingham risk score. NP was inferred using The Douleur Neuropathique 4 clinical examination, and MH- was assessed using the five-item Mental Health Inventory questionnaire. Cardiovascular autonomic function was determined from peak heart rate during maximal exercise (HRpeak). RESULTS: There was a high prevalence of both NP (39%) and MH- (45%) following SCI. MH- was significantly correlated with an adverse CVD risk profile (r = 0.174; p = 0.01), increased the odds of adverse 30-year CVD risk by 2.2 (CI 0.92-2.81, p = 0.02), and is an important variable in determining CVD risk (importance=0.74, p = 0.05). Females (p = 0.05) and those with a higher HRpeak (p = 0.046) tended to be more likely to have NP. CONCLUSIONS: Clinical measures of MH-, but not NP, are important factors for increased CVD risk following SCI. NP tended to be more prevalent in those with more preserved cardiovascular autonomic function. The interrelationships between secondary consequences of SCI are complex and need further exploration.

Faintly tired: a systematic review of fatigue in patients with orthostatic syncope.

BACKGROUND: Orthostatic syncope (transient loss of conscious when standing-fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing fatigue, sometimes with "brain fog", which may further impact their quality of life, but the incidence and severity of fatigue in patients with syncope remain unclear. In this systematic review, we report evidence on the associations between fatigue and conditions of orthostatic syncope. METHODS: We performed a comprehensive literature search of four academic databases to identify articles that evaluated the association between orthostatic syncope [postural orthostatic tachycardia syndrome (POTS), vasovagal syncope (VVS), orthostatic hypotension (OH)] and fatigue. Studies were independently screened using a multi-stage approach by two researchers to maintain consistency and limit bias. RESULTS: Our initial search identified 2797 articles, of which 13 met our inclusion criteria (POTS n = 10; VVS n = 1; OH n = 1; VVS and POTS n = 1). Fatigue scores were significantly higher in patients with orthostatic syncope than healthy controls, and were particularly severe in those with POTS. Fatigue associated with orthostatic syncope disorders spanned multiple domains, with each dimension contributing equally to increased fatigue. "Brain fog" was an important symptom of POTS, negatively affecting productivity and cognition. Finally, fatigue was negatively associated with mental health in patients with POTS. CONCLUSION: In conditions of orthostatic syncope, fatigue is prevalent and debilitating, especially in patients with POTS. The consideration of fatigue in patients with orthostatic disorders is essential to improve diagnosis and management of symptoms, thus improving quality of life for affected individuals.

The effect of water temperature on orthostatic tolerance: a randomised crossover trial.

PURPOSE: Bolus water drinking, at room temperature, has been shown to improve orthostatic tolerance (OT), probably via sympathetic activation; however, it is not clear whether the temperature of the water bolus modifies the effect on OT or the cardiovascular responses to orthostatic stress. The aim of this study was to assess whether differing water temperature of the water bolus would alter time to presyncope and/or cardiovascular parameters during incremental orthostatic stress. METHODS: Fourteen participants underwent three head-up tilt (HUT) tests with graded lower body negative pressure (LBNP) continued until presyncope. Fifteen minutes prior to each HUT, participants drank a 500 mL bolus of water which was randomised, in single-blind crossover fashion, to either room temperature water (20 °C) (ROOM), ice-cold water (0-3 °C) (COLD) or warm water (45 °C) (WARM). Cardiovascular parameters were monitored continuously. RESULTS: There was no significant difference in OT in the COLD (33 ± 3 min; p = 0.3321) and WARM (32 ± 3 min; p = 0.6764) conditions in comparison to the ROOM condition (31 ± 3 min). During the HUT tests, heart rate and cardiac output were significantly reduced (p < 0.0073), with significantly increased systolic blood pressure, stroke volume, cerebral blood flow velocity and total peripheral resistance (p < 0.0054), in the COLD compared to ROOM conditions. CONCLUSIONS: In healthy controls, bolus cold water drinking results in favourable orthostatic cardiovascular responses during HUT/LBNP without significantly altering OT. Using a cold water bolus may result in additional benefits in patients with orthostatic intolerance above those conferred by bolus water at room temperature (by ameliorating orthostatic tachycardia and enhancing vascular resistance responses). Further research in patients with orthostatic intolerance is warranted.

Barriers and facilitators to changing bowel care practices after spinal cord injury: a Theoretical Domains Framework approach.

BACKGROUND: Improvement to autonomic processes such as bladder, bowel and sexual function are prioritised by individuals with spinal cord injury (SCI). Bowel care is associated with high levels of dissatisfaction and decreased quality of life. Despite dissatisfaction, 71% of individuals have not changed their bowel care routine for at least 5 years, highlighting a disconnect between dissatisfaction with bowel care and changing routines to optimise bowel care. OBJECTIVE: Using an integrated knowledge translation approach, we aimed to explore the barriers and facilitators to making changes to bowel care in individuals with SCI. METHODS: Our approach was guided by the Behaviour Change Wheel and used the Theoretical Domains Framework (TDF). Semi-structured interviews were conducted with individuals with SCI (n = 13, mean age 48.6 ± 13.1 years) and transcribed verbatim (duration 31.9 ± 7.1 min). Barriers and facilitators were extracted, deductively coded using TDF domains and inductively analysed for themes within domains. RESULTS: Changing bowel care after SCI was heavily influenced by four TDF domains: environmental context and resources (workplace flexibility, opportunity or circumstance, and access to resources); beliefs about consequences; social influences (perceived support and peer mentorship); and knowledge (knowledge of physiological processes and bowel care options). All intervention functions and policy categories were considered viable intervention options, with human (61%) and digital (33%) platforms preferred. CONCLUSIONS: Modifying bowel care is a multi-factorial behaviour. These findings will support the systematic development and implementation of future interventions to both enable individuals with SCI to change their bowel care and to facilitate the optimisation of bowel care approaches.

Forearm vascular resistance responses to the Valsalva maneuver in healthy young and older adults.

PURPOSE: Effective end-organ peripheral vascular resistance responses are critical to blood pressure control while upright, and prevention of syncope (fainting). The Valsalva maneuver (VM) induces blood pressure decreases that evoke baroreflex-mediated vasoconstriction. We characterized beat-to-beat forearm vascular resistance (FVR) responses to the VM in healthy adults, evaluated the impact of age and sex on these responses, and investigated their association with orthostatic tolerance (OT; susceptibility to syncope). We hypothesized that individuals with smaller FVR responses would be more susceptible to syncope. METHODS: Healthy young (N = 36; 19 women; age 25.4 ± 4.6 years) and older (N = 21; 12 women; age 62.4 ± 9.6 years) adults performed a supine 40 mmHg, 20 s VM. Graded 60° head-up-tilt with combined lower body negative pressure continued to presyncope was used to determine OT. Non-invasive beat-to-beat blood pressure and heart rate (finger plethysmography) were recorded continuously. FVR was calculated as mean arterial pressure (MAP) divided by brachial blood flow velocity (Doppler ultrasound) relative to baseline. RESULTS: The VM produces a distinctive FVR pattern that peaks (+137.1 ± 11.6%) in phase 2B (17.5 ± 0.3 s) as the baroreflex responds to low-pressure perturbations. This response increased with age overall (p < 0.001) and within male (p = 0.030) and female subgroups (p < 0.001). Maximum FVR during the VM was significantly correlated with maximal tilt FVR (r = 0.364; p = 0.0153) and with OT when expressed relative to the MAP decrease in phase 2A (Max FVR (%)/MAP2A-1; r = 0.337; p = 0.0206). CONCLUSION: This is the first characterization of FVR responses to the VM. The VM elicits large baroreflex-mediated increases in FVR; small FVR responses to the VM may indicate susceptibility to syncope.

Long-COVID postural tachycardia syndrome: an American Autonomic Society statement.

COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.

Diagnostic criteria for initial orthostatic hypotension: a narrative review.

Abnormalities in orthostatic blood pressure changes upon active standing are associated with morbidity, mortality, and reduced quality of life. However, over the last decade, several population-based cohort studies have reported a remarkably high prevalence (between 25 and 70%) of initial orthostatic hypotension (IOH) among elderly individuals. This has raised the question as to whether the orthostatic blood pressure patterns in these community-dwelling elderly should truly be considered as pathological. If not, redefining of the systolic cutoff values for IOH (i.e., a value ≥ 40 mmHg in systolic blood pressure in the first 15 s after standing up) might be necessary to differ between normal aging and true pathology. Therefore, in this narrative review, we provide a critical analysis of the current reference values for the changes in systolic BP in the first 60 s after standing up and discuss how these values should be applied to large population studies. We will address factors that influence the magnitude of the systolic blood pressure changes following active standing and the importance of standardization of the stand-up test, which is a prerequisite for quantitative, between-subject comparisons of the postural hemodynamic response.

Evaluation of cardiovascular disease risk in individuals with chronic spinal cord injury.

STUDY DESIGN: Multicentre, cross-sectional study. OBJECTIVES: To identify which markers of obesity, injury characteristics and autonomic function variables are related to cardiovascular disease (CVD) risk after spinal cord injury (SCI), and establish cut-points for detection and risk management. SETTING: Eight SCI rehabilitation centres in the Netherlands. METHODS: Individuals (n = 257) with a traumatic, chronic (≥10 years) SCI, with age at injury between 18 and 35 years, completed a self-report questionnaire and a one-day visit to a rehabilitation centre for testing. Three anthropometric measures were tested: body mass index (BMI); waist circumference (WC); and waist-to-height ratio (WHtR). Injury characteristics included: American Spinal Injury Association impairment scale (AIS); duration of injury (DOI); and neurological level of injury (LOI). Cardiovascular autonomic function was assessed from peak heart rate during maximal exercise (HRpeak). Systolic arterial pressure (SAP) and aerobic capacity (VO2peak) were also determined. CVD risk was calculated using the Framingham risk score (FRS). RESULTS: All anthropometric variables were associated with FRS, with WC showing the strongest correlation (r = 0.41, p < 0.001) and greatest area under the curve (0.73) for 10-year CVD risk (%). WC, DOI, SAP, HRpeak, LOI, and VO2peak (variable importance: 0.81, 1.0, 0.98, 0.98, 0.66, 0.68, respectively) were important predictive variables for 10-year CVD risk in individuals with SCI. CONCLUSIONS: We confirm that WC is a simple, practical measure of CVD risk, and along with DOI and markers of cardiovascular autonomic function, plays a role in the increased CVD risk following SCI.

The hERG channel activator, RPR260243, enhances protective IKr current early in the refractory period reducing arrhythmogenicity in zebrafish hearts.

Human ether-à-go-go related gene (hERG) K+ channels are important in cardiac repolarization, and their dysfunction causes prolongation of the ventricular action potential, long QT syndrome, and arrhythmia. As such, approaches to augment hERG channel function, such as activator compounds, have been of significant interest due to their marked therapeutic potential. Activator compounds that hinder channel inactivation abbreviate action potential duration (APD) but carry risk of overcorrection leading to short QT syndrome. Enhanced risk by overcorrection of the APD may be tempered by activator-induced increased refractoriness; however, investigation of the cumulative effect of hERG activator compounds on the balance of these effects in whole organ systems is lacking. Here, we have investigated the antiarrhythmic capability of a hERG activator, RPR260243, which primarily augments channel function by slowing deactivation kinetics in ex vivo zebrafish whole hearts. We show that RPR260243 abbreviates the ventricular APD, reduces triangulation, and steepens the slope of the electrical restitution curve. In addition, RPR260243 increases the post-repolarization refractory period. We provide evidence that this latter effect arises from RPR260243-induced enhancement of hERG channel-protective currents flowing early in the refractory period. Finally, the cumulative effect of RPR260243 on arrhythmogenicity in whole organ zebrafish hearts is demonstrated by the restoration of normal rhythm in hearts presenting dofetilide-induced arrhythmia. These findings in a whole organ model demonstrate the antiarrhythmic benefit of hERG activator compounds that modify both APD and refractoriness. Furthermore, our results demonstrate that targeted slowing of hERG channel deactivation and enhancement of protective currents may provide an effective antiarrhythmic approach.NEW & NOTEWORTHY hERG channel dysfunction causes long QT syndrome and arrhythmia. Activator compounds have been of significant interest due to their therapeutic potential. We used the whole organ zebrafish heart model to demonstrate the antiarrhythmic benefit of the hERG activator, RPR260243. The activator abbreviated APD and increased refractoriness, the combined effect of which rescued induced ventricular arrhythmia. Our findings show that the targeted slowing of hERG channel deactivation and enhancement of protective currents caused by the RPR260243 activator may provide an effective antiarrhythmic approach.

Autonomic function testing in the COVID-19 pandemic: an American Autonomic Society position statement.

COVID-19 is a global pandemic that is wreaking havoc with the health and economy of much of human civilization. In this document from the American Autonomic Society, we identify the potential risks of exposure to patients, physicians, and allied healthcare staff. We provide guidance for conducting autonomic function testing safely in this environment.

Human papillomavirus (HPV) vaccine and autonomic disorders: a position statement from the American Autonomic Society.

INTRODUCTION: Human papillomavirus (HPV) vaccination has been anecdotally connected to the development of dysautonomia, chronic fatigue, complex regional pain syndrome and postural tachycardia syndrome. OBJECTIVES: To critically evaluate a potential connection between HPV vaccination and the above-noted conditions. METHODS: We reviewed the literature containing the biology of the virus, pathophysiology of infection, epidemiology of associated cancers, indications of HPV vaccination, safety surveillance data and published reports linking HPV vaccination to autonomic disorders. RESULTS: At this time, the American Autonomic Society finds that there are no data to support a causal relationship between HPV vaccination and CRPS, chronic fatigue, and postural tachycardia syndrome to other forms of dysautonomia. CONCLUSION: Certain conditions are prevalent in the same populations that are vaccinated with the HPV vaccine (peri-pubertal males and females). This association, however, is an insufficient proof of causality.

Clinical recommendations for use of lidocaine lubricant during bowel care after spinal cord injury prolong care routines and worsen autonomic dysreflexia: results from a randomised clinical trial.

STUDY DESIGN: Clinical trial. OBJECTIVE: Spinal cord injury (SCI) impacts autonomic function and bowel management. Bowel care is a potential trigger for autonomic dysreflexia (AD; paroxysmal hypertension elicited by sensory stimuli below the level of lesion). AD can be life threatening so strategies to minimise AD are prioritised after SCI. Lidocaine lubricant is recommended during bowel care with the rationale to minimise the sensory stimulus, reducing AD. The objective of this study was to assess whether lidocaine lubricant (Xylocaine 2%) ameliorates AD during at-home bowel care compared with standard lubricant (placebo). SETTING: Community. METHOD: Participants (n = 13; age 44.0 ± 3.3 years) with high-level SCI (C3-T4) performed their normal at-home bowel care on two days, each time using a different lubricant, with continuous non-invasive cardiovascular monitoring. Injury to spinal autonomic (sympathetic) nerves was determined from low-frequency systolic arterial pressure (LF SAP) variability. RESULTS: Participants displayed reduced autonomic function (LF SAP 3.02 ± 0.84 mmHg2), suggesting impaired autonomic control. Bowel care duration was increased with lidocaine (79.1 ± 10.0 min) compared to placebo (57.7 ± 6.3 min; p = 0.018). All participants experienced AD on both days, but maximum SAP was higher with lidocaine (214.3 ± 10.5 mmHg) than placebo (196.7 ± 10.0 mmHg; p = 0.046). Overall, SAP was higher for longer with lidocaine (6.5 × 105 ± 0.9 × 105 mmHg • beat) than placebo (4.4 × 105 ± 0.6 × 105 mmHg • beat; p = 0.018) indicating a higher burden of AD. Heart rate and rhythm disturbances were increased during AD, particularly with lidocaine use. CONCLUSIONS: At-home bowel care was a potent trigger for AD. Our findings contradict recommendations for lidocaine use during bowel care, suggesting that anaesthetic lubricants impair reflex bowel emptying, resulting in longer care routines with an increased burden of AD.

Autonomic Parameter and Stress Profile Predict Secondary Ischemic Events After Transient Ischemic Attack or Minor Stroke.

Background and Purpose- Traditional risk factors for ischemic stroke are body stressors that are related to autonomic autonomic system (ANS) dysfunction. The value of ABCD2 score (age, blood pressure, clinical features, duration of symptoms, diabetes) to predict ischemic stroke after transient ischemic attack is compromised by the inclusion of a limited number of stressors. We aimed to assess whether markers of ANS function and stress could predict the occurrence of secondary ischemic events after transient ischemic attack or minor stroke. Methods- This is a prospective cohort study in which 201 patients were recruited within 48 hours after initial transient ischemic attack or minor stroke and followed for 90 days to assess the development of secondary ischemic events. ABCD2 score, heart rate variability (HRV) parameters as markers of ANS function, and psychological stress were assessed. Logistic regression and area under the curve (AUC) were used to assess the models' predictive ability. Results- Morning high frequency (HF) HRV power and changes in HF HRV from morning to afternoon (daytime HF changes) were the most useful HRV predictors for both ischemic events (AUC=0.61 and 0.70) and ischemic stroke (AUC=0.62 and 0.72). Compared with ABCD2 score, 2 HRV-based stress models showed higher predictive ability for ischemic events (AUC=0.82 versus 0.63, 0.76 versus 0.63; P<0.05) and ischemic stroke (AUC=0.87 versus 0.64, 0.82 versus 0.64; P<0.05). Conclusions- Assessing the effects of stress on the ANS may be an innovative way to stratify the risk of ischemic events after transient ischemic attack or minor stroke. New risk stratification by assessing the dynamic features of ANS dysfunction and stress may help identify high-risk sub-populations that may benefit from added management.

A Longitudinal Study of the Association of Clinical Indices of Cardiovascular Autonomic Function with Breast Cancer Treatment and Exercise Training.

BACKGROUND: Cardiovascular autonomic dysfunction is an early marker for cardiovascular disease. Anthracycline chemotherapy and left-sided radiation for breast cancer are associated with negative autonomic function changes. This study's objectives were to characterize changes in, and the association of exercise training with, clinical indices of cardiovascular autonomic function across the trajectory of breast cancer therapy. SUBJECTS, MATERIALS, AND METHODS: Seventy-three patients receiving adjuvant chemotherapy participated to varying degrees in supervised aerobic and resistance exercise during chemotherapy ± radiation and for 20 weeks after. Resting heart rate (HRrest) and blood pressure were measured weekly during chemotherapy. HRrest, exercise heart rate recovery (HRrecovery), and aerobic fitness were measured at enrollment, end of chemotherapy ± radiation, and 10 and 20 weeks after treatment. RESULTS: During chemotherapy, HRrest increased in a parabolic manner within a single treatment and with increasing treatment dose, whereas systolic and diastolic blood pressure decreased linearly across treatments. Tachycardia and hypotension were present in 32%-51% of participants. Factors associated with weekly changes during chemotherapy included receiving anthracyclines or trastuzumab, days since last treatment, hematocrit, and exercise attendance. Receipt of anthracyclines, trastuzumab, and left-sided radiation individually predicted impairments of HRrest and HRrecovery during chemotherapy ± radiation; however, aerobic fitness change and at least twice-weekly exercise attendance predicted improvement. By 10 weeks after treatment, HRrest and blood pressure were not different from prechemotherapy. CONCLUSION: In this study, chemotherapy resulted in increased HRrest and tachycardia, as well as decreased blood pressure and hypotension. Anthracyclines, trastuzumab, and left-sided radiation were associated with HRrest elevations and impairments of HRrecovery, but exercise training at least twice a week appeared to mitigate these changes. IMPLICATIONS FOR PRACTICE: This study characterized changes in clinically accessible measures with well-established prognostic value for cardiovascular disease, and investigated associations with cardiotoxic treatments and the positive influence of exercise. The chemotherapy-related incremental increase in resting heart rate, with tachycardia occurring in one third of patients, and decrease in blood pressure, with hypotension occurring in one half of the patients, is relevant to oncology practitioners for clinical examination or patient report of related symptoms (i.e., dizziness). The weekly dose of two 60-minute sessions of moderate-intensity aerobic and resistance exercise that was identified as protective of cardiovascular autonomic impairments can easily be prescribed to patients by oncologists.

Relationships between orthostatic hypotension, frailty, falling and mortality in elderly care home residents.

BACKGROUND: Orthostatic hypotension (OH; profound falls in blood pressure when upright) is a common deficit that increases in incidence with age, and may be associated with falling risk. Deficit accumulation results in frailty, regarded as enhanced vulnerability to adverse outcomes. We aimed to evaluate the relationships between OH, frailty, falling and mortality in elderly care home residents. METHODS: From the Minimum Data Set (MDS) document, a frailty index (FI-MDS) was generated from a list of 58 deficits, ranging from 0 (no deficits) to 1.0 (58 deficits). OH was evaluated from beat-to-beat blood pressure and heart rate (finger plethysmography) collected during a 15-min supine-seated orthostatic stress test. Retrospective and prospective falling rates (falls/year) were extracted from facility falls incident reports. All-cause 3-year mortality was determined. Data are reported as mean ± standard error. RESULTS: Data were obtained from 116 older adults (aged 84.2 ± 0.9 years; 44% males) living in two long term care facilities. The mean FI-MDS was 0.36 ± 0.01; FI-MDS was correlated with age (r = 0.277; p = 0.003). Those who were frail (FI ≥ 0.27) had larger Initial (- 17.8 ± 4.2 vs - 6.1 ± 3.3 mmHg, p = 0.03) and Consensus (- 22.7 ± 4.3 vs - 11.5 ± 3.3 mmHg, p = 0.04) orthostatic reductions in systolic arterial pressure. Frail individuals had higher prospective and retrospective falling rates and higher 3-year mortality. Receiver operating characteristic curves evaluated the ability of FI-MDS alone to predict prospective falls (sensitivity 72%, specificity 36%), Consensus OH (sensitivity 68%, specificity 60%) and 3-year mortality (sensitivity 77%, specificity 49%). Kaplan Meier survival analyses showed significantly higher 3-year mortality in those who were frail compared to the non-frail (p = 0.005). CONCLUSIONS: Frailty can be captured using a frailty index based on MDS data in elderly individuals living in long term care, and is related to susceptibility to orthostatic hypotension, falling risk and 3-year mortality. Use of the MDS to generate a frailty index may represent a simple and convenient risk assessment tool for older adults living in long term care. Older adults who are both frail and have impaired orthostatic blood pressure control have a particularly high risk of falling and should receive tailored management to mitigate this risk.