Multiscale analysis of heart rate variability in non-stationary environments

Abstract:

Heart rate variability (HRV) is highly non-stationary, even if no perturbing influences can be identified during the recording of the data. The non-stationarity becomes more profound when HRV data are measured in intrinsically non-stationary environments, such as social stress. In general, HRV data measured in such situations are more difficult to analyze than those measured in constant environments.

In this paper, we analyze HRV data measured during a social stress test using two multiscale approaches, the adaptive fractal analysis (AFA) and scale-dependent Lyapunov exponent (SDLE), for the purpose of uncovering differences in HRV between chronic fatigue syndrome (CFS) patients and their matched-controls.

CFS is a debilitating, heterogeneous illness with no known biomarker. HRV has shown some promise recently as a non-invasive measure of subtle physiological disturbances and trauma that are otherwise difficult to assess. If the HRV in persons with CFS are significantly different from their healthy controls, then certain cardiac irregularities may constitute good candidate biomarkers for CFS.

Our multiscale analyses show that there are notable differences in HRV between CFS and their matched controls before a social stress test, but these differences seem to diminish during the test. These analyses illustrate that the two employed multiscale approaches could be useful for the analysis of HRV measured in various environments, both stationary and non-stationary.

 

Source: Gao J, Gurbaxani BM, Hu J, Heilman KJ, Emanuele Ii VA, Lewis GF, Davila M, Unger ER, Lin JM. Multiscale analysis of heart rate variability in non-stationary environments. Front Physiol. 2013 May 30;4:119. doi: 10.3389/fphys.2013.00119. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667239/ (Full article)

 

Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome

Abstract:

BACKGROUND: Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS.

METHODS: Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between-group differences in autonomic reactivity and associations with cognitive performance were analysed.

RESULTS: Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes.

CONCLUSIONS: These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.

 

Source: Beaumont A, Burton AR, Lemon J, Bennett BK, Lloyd A, Vollmer-Conna U. Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome. PLoS One. 2012;7(11):e49518. doi: 10.1371/journal.pone.0049518. Epub 2012 Nov 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498107/ (Full article)

 

Responses to exercise differ for chronic fatigue syndrome patients with fibromyalgia

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are chronic multisymptom illnesses with substantial clinical and diagnostic overlap. We have previously shown that, when controlling for aerobic fitness and accounting for comorbid FM, CFS patients do not exhibit abnormal cardiorespiratory responses during maximal aerobic exercise compared with healthy controls, despite differences in pain and exertion.

PURPOSE: The purpose of the present study was to examine cardiac and perceptual responses to steady-state submaximal exercise in CFS patients and healthy controls.

METHODS: Twenty-one CFS patients (13 CFS with comorbid FM (CFS + FM)) and 14 controls completed 20 min of submaximal cycling exercise. Impedance cardiography was used to determine cardiac responses during exercise. Systolic blood pressure (SBP), RPE, and leg muscle pain were also measured. Data were analyzed using a doubly multivariate, repeated-measures MANOVA to model the exercise response.

RESULTS: There was a significant multivariate time-by-group interaction (P < 0.05). The CFS + FM group exhibited an exercise response characterized by higher stroke index, ventilatory equivalents for oxygen and carbon dioxide and RPE, lower SBP, and similar HR responses compared to controls.

CONCLUSIONS: The present results extend on our previous work with maximal exercise and show that CFS and CFS + FM differ in their responses to steady-state exercise. These results highlight the importance of accounting for comorbid conditions when conducting CFS research, particularly when examining psychophysiological responses to exercise.

 

Source: Cook DB, Stegner AJ, Nagelkirk PR, Meyer JD, Togo F, Natelson BH. Responses to exercise differ for chronic fatigue syndrome patients with fibromyalgia. Med Sci Sports Exerc. 2012 Jun;44(6):1186-93. doi: 10.1249/MSS.0b013e3182417b9a. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319493/ (Full article)

 

Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: The etiology of chronic fatigue syndrome (CFS) is unknown. Orthostatic intolerance (OI) is common in CFS patients. Recently, small heart with low cardiac output has been postulated to be related to the genesis of both CFS and OI.

HYPOTHESIS: Small heart is associated with OI in patients with CFS.

METHODS: Study CFS patients were divided into groups of 26 (57%) CFSOI(+) and 20 (43%) CFSOI(-) according to the presence or absence of OI. In addition, 11 OI patients and 27 age- and sex-matched control subjects were studied. Left ventricular (LV) dimensions and function were determined echocardiographically.

RESULTS: The mean values of cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic dimension, LV end-systolic dimension, stroke volume index, cardiac index, and LV mass index were all significantly smaller in CFSOI(+) patients than in CFSOI(-) patients and healthy controls, and also in OI patients than in controls. A smaller LV end-diastolic dimension (<40 mm) was significantly (P<0.05) more prevalently noted in CFSOI(+) (54%) and OI (45%) than in CFSOI(-) (5%) and controls (4%). A lower cardiac index (<2 L/min/mm(2)) was more prevalent in CFSOI(+) (65%) than in CFSOI(-) (5%, P<0.01), OI (27%), and controls (11%, P<0.01).

CONCLUSIONS: A small size of LV with low cardiac output was noted in OI, and its degree was more pronounced in CFSOI(+). A small heart appears to be related to the genesis of OI and CFS via both cerebral and systemic hypoperfusion. CFSOI(+) seems to constitute a well-defined and predominant subgroup of CFS.

© 2011 Wiley Periodicals, Inc.

 

Source: Miwa K, Fujita M. Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome. Clin Cardiol. 2011 Dec;34(12):782-6. doi: 10.1002/clc.20962. Epub 2011 Nov 28. http://onlinelibrary.wiley.com/doi/10.1002/clc.20962/full (Full article)

 

Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging

Abstract:

OBJECTIVES: Impaired cardiac function has been confirmed in patients with chronic fatigue syndrome (CFS). Magnetic resonance cardiac tagging is a novel technique that assesses myocardial wall function in vivo. We hypothesized that patients with CFS may have impaired development and release of myocardial torsion and strain.

METHODS: Cardiac morphology and function were assessed using magnetic resonance imaging and cardiac tagging methodology in 12 CFS patients (Fukuda) and 10 matched controls.

RESULTS: Compared to controls, the CFS group had substantially reduced left ventricular mass (reduced by 23%), end-diastolic volume (30%), stroke volume (29%) and cardiac output (25%). Residual torsion at 150% of the end-systolic time was found to be significantly higher in the patients with CFS (5.3 ± 1.6°) compared to the control group (1.7 ± 0.7°, P = 0.0001). End-diastolic volume index correlated negatively with both torsion-to-endocardial-strain ratio (TSR) (r = -0.65, P = 0.02) and the residual torsion at 150% end-systolic time (r = -0.76, P = 0.004), so decreased end-diastolic volume is associated with raised TSR and torsion persisting longer into diastole. Reduced end-diastolic volume index also correlated significantly with increased radial thickening (r = -0.65, P = 0.03) and impaired diastolic function represented by the ratio of early to late ventricular filling velocity (E/A ratio, r = 0.71, P = 0.009) and early filling percentage (r = 0.73, P = 0.008).

CONCLUSION: Patients with CFS have markedly reduced cardiac mass and blood pool volumes, particularly end-diastolic volume: this results in significant impairments in stroke volume and cardiac output compared to controls. The CFS group appeared to have a delay in the release of torsion.

© 2011 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Hollingsworth KG, Hodgson T, Macgowan GA, Blamire AM, Newton JL. Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging. J Intern Med. 2012 Mar;271(3):264-70. doi: 10.1111/j.1365-2796.2011.02429.x. Epub 2011 Aug 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627316/ (Full article)

 

Autonomic hyper-vigilance in post-infective fatigue syndrome

Abstract:

This study examined whether post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges.

We studied 23 patients with PIFS and 25 healthy matched control subjects. A heartbeat discrimination task and a pressure pain threshold test were used to assess interoceptive sensitivity. Cardiac response was assessed over a 4-min Stroop task. PIFS was associated with higher accuracy in heartbeat discrimination and a lower pressure pain threshold. Increased interoceptive sensitivity correlated strongly with current symptoms and potentiated differences in the cardiac response to the Stroop task, which in PIFS was characterized by insensitivity to task difficulty and lack of habituation.

Our results provide the first evidence of heightened interoceptive sensitivity in PIFS. Together with the distinct pattern in cardiac responsivity these findings present a picture of physiological hyper-vigilance and response inflexibility.

Copyright (c) 2010 Elsevier B.V. All rights reserved.

 

Source: Kadota Y, Cooper G, Burton AR, Lemon J, Schall U, Lloyd A, Vollmer-Conna U/ Autonomic hyper-vigilance in post-infective fatigue syndrome. Biol Psychol. 2010 Sep;85(1):97-103. doi: 10.1016/j.biopsycho.2010.05.009. Epub 2010 Jun 2. https://www.ncbi.nlm.nih.gov/pubmed/20678991

 

Impaired cardiovascular response to standing in chronic fatigue syndrome

Abstract:

BACKGROUND: Impaired skeletal muscle metabolism is recognized in chronic fatigue syndrome (CFS). This study examined the relationship between skeletal and cardiac muscle function and symptoms on standing in CFS using magnetic resonance spectroscopy (MRS) and impedance cardiography.

MATERIALS AND METHODS: Phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio by cardiac MRS, PCr/ADP and proton efflux by muscle MRS were performed in 12 CFS (Fukuda) and 8 controls. Head up tilt (HUT) and cardiac contractility (left ventricular work index, LVWI) (n = 64 CFS and matched controls) were found. Fatigue impact was accessed by Fatigue Impact Scale and orthostatic symptoms by Orthostatic Grading Scale (OGS).

RESULTS: Cardiac PCr/ATP correlated with measures of muscle bioenergetic function (half-time PCr recovery [kappa = -0.71, P = 0.005] and half-time ADP recovery [kappa = -0.60, P = 0.02]) suggesting that the muscle and cardiac bioenergetic function correlate in CFS. Four of 12 (33.3%) CFS patients had PCr/ATP values consistent with significant cardiac impairment. Those with impaired cardiac energy metabolism had significantly reduced maximal and initial proton efflux rates (P < 0.05). Cardiac PCr/ATP ratio correlated with myocardial contractility (LVWI) in response to standing (P = 0.03). On HUT, LVWI on standing was significantly higher in CFS (P = 0.05) with symptoms on standing (OGS) occurring in 61/64 (95%) (vs. 25/64 [39%] controls; P < 0.0001). OGS scores were significantly higher in those with abnormal LVWI responses to standing (P = 0.04), with the LVWI on standing correlating with OGS scores (r(2) = 0.1; P = 0.03). HUT was positive in 19 (32%).

CONCLUSIONS: Skeletal muscle and cardiac bioenergetic abnormalities associate in CFS. Cardiac bioenergetic metabolism associates with increase in cardiac contractility on standing. Haemodynamic assessment in CFS is well tolerated and safe with a high diagnostic yield comparable with unexplained syncope.

 

Source: Hollingsworth KG, Jones DE, Taylor R, Blamire AM, Newton JL. Impaired cardiovascular response to standing in chronic fatigue syndrome. Eur J Clin Invest. 2010 Jul;40(7):608-15. doi: 10.1111/j.1365-2362.2010.02310.x. Epub 2010 May 23. https://www.ncbi.nlm.nih.gov/pubmed/20497461

 

Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS

Abstract:

There is evidence that disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways and a lowered antioxidant status are important pathophysiological mechanisms underpinning myalgic encephalomyelitis / chronic fatigue syndrome(ME/CFS). Important precipitating and perpetuating factors for ME/CFS are (amongst others) bacterial and viral infections; bacterial translocation due to an increased gut permeability; and psychological stress.

Recently, Jason et al (2006) reported that the mean age of patients with myalgic encephalomyelitis/chronic fatigue syndrome dying from heart failure, i.e. 58.7 years, is significantly lower than the age of those dying from heart failure in the general US population, i.e. 83.1 years. These findings implicate that ME/CFS is a risk factor to cardio-vascular disorder.

This review demonstrates that disorders in various IO&NS pathways provide explanations for the earlier mortality due to cardiovascular disorders in ME/CFS. These pathways are: a) chronic low grade inflammation with extended production of nuclear factor kappa B and COX-2 and increased levels of tumour necrosis factor alpha; b) increased O&NS with increased peroxide levels, and phospholipid oxidation including oxidative damage to phosphatidylinositol; c) decreased levels of specific antioxidants, i.e. coenzyme Q10, zinc and dehydroepiandrosterone-sulphate; d) bacterial translocation as a result of leaky gut; e) decreased omega-3 polyunsatutared fatty acids (PUFAs), and increased omega-6 PUFA and saturated fatty acid levels; and f) the presence of viral and bacterial infections and psychological stressors. The mechanisms whereby each of these factors may contribute towards cardio-vascular disorder in ME/CFS are discussed.

ME/CFS is a multisystemic metabolic-inflammatory disorder. The aberrations in IO&NS pathways may increase the risk for cardiovascular disorders.

 

Source: Maes M, Twisk FN. Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS. Neuro Endocrinol Lett. 2009;30(6):677-93. https://www.ncbi.nlm.nih.gov/pubmed/20038921

 

Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder

Abstract:

INTRODUCTION: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medical illness characterized by disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways.

METHODS: This paper examines the role of Coenzyme Q10 (CoQ10), a mitochondrial nutrient which acts as an essential cofactor for the production of ATP in mitochondria and which displays significant antioxidant activities. Plasma CoQ10 has been assayed in 58 patients with ME/CFS and in 22 normal controls; the relationships between CoQ10 and the severity of ME/CFS as measured by means of the FibroFatigue (FF) scale were measured.

RESULTS: Plasma CoQ10 was significantly (p=0.00001) lower in ME/CFS patients than in normal controls. Up to 44.8% of patients with ME/CFS had values beneath the lowest plasma CoQ10 value detected in the normal controls, i.e. 490 microg/L. In ME/CFS, there were significant and inverse relationships between CoQ10 and the total score on the FF scale, fatigue and autonomic symptoms. Patients with very low CoQ10 (<390 microg/L) suffered significantly more from concentration and memory disturbances.

DISCUSSION: The results show that lowered levels of CoQ10 play a role in the pathophysiology of ME/CFS and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by CoQ10 depletion. Our results suggest that patients with ME/CFS would benefit from CoQ10 supplementation in order to normalize the low CoQ10 syndrome and the IO&NS disorders. The findings that lower CoQ10 is an independent predictor of chronic heart failure (CHF) and mortality due to CHF may explain previous reports that the mean age of ME/CFS patients dying from CHF is 25 years younger than the age of those dying from CHF in the general population. Since statins significantly decrease plasma CoQ10, ME/CFS should be regarded as a relative contraindication for treatment with statins without CoQ10 supplementation.

 

Source: Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett. 2009;30(4):470-6. https://www.ncbi.nlm.nih.gov/pubmed/20010505

 

Cardiovascular dysfunction with low cardiac output due to a small heart in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: Little attention has been paid to possible cardiovascular involvement in patients with chronic fatigue syndrome (CFS), although many of their symptoms and signs suggest cardiovascular dysfunction. Possible cardiovascular symptoms and cardiac function were investigated in CFS patients.

METHODS: Cardiovascular symptoms were intensively investigated and cardiac function was evaluated echocardiographically.

PATIENTS: Fifty-three patients (23 men and 30 women, mean age: 31+/-7 years) with CFS under 50 years were studied.

RESULTS: Slender build (body mass index <20 kg/m(2)) was common (47%). Possible cardiovascular symptoms including shortness of breath (32%), dyspnea on effort (28%), rapid heartbeat (38%), chest pain (43%), fainting (43%), orthostatic dizziness (45%) and coldness of feet (42%), were all frequent complaints. Hypotension (28%) was occasionally noted. Electrocardiograms frequently revealed right axis deviation (21%) and severe sinus arrhythmia (34%) suggesting accentuated parasympathetic nervous activity. Small heart shadow (cardiothoracic ratio <or=42%) was noted on the chest roentgenogram in 32 patients (60%). Echocardiographic examination demonstrated low cardiac indexes (<2 L/min/m(2)) with low stroke volume indexes (<30 mL/m(2)) due to a small left ventricular chamber in 19 (36%, p<0.05 vs. 8% in 36 controls). None had reduced left ventricular ejection fraction.

CONCLUSION: Cardiovascular symptoms are common in CFS patients. Cardiac dysfunction with low cardiac output due to small left ventricular chamber may contribute to the development of chronic fatigue as a constitutional factor in a considerable number of CFS patients.

 

Source: Miwa K, Fujita M. Cardiovascular dysfunction with low cardiac output due to a small heart in patients with chronic fatigue syndrome. Intern Med. 2009;48(21):1849-54. Epub 2009 Nov 2. https://www.ncbi.nlm.nih.gov/pubmed/19881233