Deep Breathing Heart Rate Variability Research Articles

Corneal nerve and nerve conduction abnormalities in children with type 1 diabetes.

In vivo corneal confocal microscopy (CCM) is a novel, rapid, and non-invasive technique that identifies early small fiber damage and can predict the progression and development of clinical neuropathy in adults with type 1 diabetes. However, its usefulness in children is not well established. This study compared corneal confocal microscopy with neuropathic symptoms, signs, and objective measures of neuropathy for the diagnosis of diabetic neuropathy in children with type 1 diabetes. A total of 83 children with type 1 diabetes and 83 healthy participants of similar age underwent assessment of neuropathy symptoms, signs, nerve conduction studies, quantitative sensory and autonomic function testing, and in vivo CCM. Only of 3/83 (4%) children with type 1 diabetes had subclinical neuropathy. However, corneal nerve fiber density (p=0.001), branch density (p=0.006), fiber length (p=0.002), tibial motor nerve amplitude and conduction velocity, and sural sensory nerve amplitude and conduction velocity (all p < 0.004) were lower in participants with type 1 diabetes than in the controls. Vibration, cooling, and warm perception thresholds and deep breathing heart rate variability were not found to be different (all p > 0.05) between children with type 1 diabetes and healthy controls. Multivariate regression analysis identified a possible association between body mass index and decreased corneal nerves. Decreased corneal nerves and abnormal nerve conduction were found in children with type 1 diabetes. CCM may allow rapid objective detection of subclinical diabetic neuropathy in children and adolescents with type 1 diabetes.

No evidence of improvement in neuropathy after renal transplantation in patients with end stage kidney disease.

To assess the impact of renal transplantation on peripheral nerve damage in patients with chronic kidney disease (CKD). Fifteen patients with CKD (eGFR <15 mL/min/1.73 m2 ) underwent longitudinal assessment after renal transplantation (age: 56.88 ± 2.53 years, eGFR: 46.82 ± 4.86) and were compared with 15 age-matched controls (age: 58.25 ± 2.18 years, eGFR: 86.0 ± 2.0). The neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration perception threshold (VPT), cold and warm sensation threshold (CST and WST), cold and heat induced pain (CIP and HIP), deep breathing heart rate variability (DB-HRV), nerve conduction studies and corneal confocal microscopy (CCM) to quantify small nerve fibre pathology, were undertaken within 1-month of renal transplantation (baseline) and at 6, 12 and 24 months of follow up. There was no significant difference in NSP (P=.1), NDS (P=.3), VPT (P=.6), CST (P=.2), CIP (P=.08), HIP (P=.1), DB-HRV (P=.9) and sural (P=.4) and peroneal (P=.1) nerve amplitude between patients with CKD and controls at baseline. However, sural (P=.04), peroneal (P=.002) and tibial (P=.007) nerve conduction velocity and tibial nerve amplitude (P=.03) were significantly lower, WST (P=.02) was significantly higher and corneal nerve fibre density (P=.004) was significantly lower in patients with CKD compared with controls. There was no significant change in NSP, NDS, quantitative sensory testing, DB-HRV, nerve conduction or CCM parameters 24 months after renal transplantation. There is evidence of small and large fibre neuropathy in patients with CKD, but no change up to 24 months after successful renal transplantation.

Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity.

Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage. Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery. Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm2) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm2) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm2) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = -0.45, P = 0.04). Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.

Autonomic dysfunction is associated with neuropsychological impairment in Lewy body disease

This study aimed to analyze the association of autonomic dysfunction with cognition, depression, apathy, and fatigue in Lewy body disease (LBD). We included 61 patients [49 with idiopathic Parkinson's disease, 7 with dementia with Lewy bodies, and 5 E46K-SNCA mutation carriers] and 22 healthy controls. All participants underwent a comprehensive battery of neuropsychological and clinical measures, autonomic symptom assessment with the SCOPA-AUT, analysis of non-invasive hemodynamic parameters during deep breathing, the Valsalva maneuver, and a 20-min tilt test, and electrochemical skin conductance measurement at rest (Sudoscan). Student's t tests were used to assess group differences, and bivariate correlations and stepwise linear regressions to explore associations between autonomic function, cognition, depression, apathy, and fatigue. Compared to controls, patients who had significant impairment (p < 0.05) in cognition, higher depression, apathy, and fatigue, more autonomic symptoms and objective autonomic dysfunction, reduced deep breathing heart rate variability [expiratory-to-inspiratory (E/I) ratio], prolonged pressure recovery time, and lower blood pressure in Valsalva late phase II and phase IV, while 24.1% had orthostatic hypotension in the tilt test. Autonomic parameters significantly correlated with cognitive and neuropsychiatric outcomes, systolic blood pressure during the Valsalva maneuver predicting apathy and depression. The E/I ratio was the main predictor of cognitive performance (17.6% for verbal fluency to 32.8% for visual memory). Cardiovascular autonomic dysfunction is associated with cognitive and neuropsychiatric impairment in LBD, heart rate variability during deep breathing and systolic blood pressure changes during the Valsalva procedure are the main predictors of neuropsychological performance and depression/apathy symptoms, respectively.

Small fibre pathology is associated with erectile dysfunction in men with type 2 diabetes.

The aim of this study was to evaluate the contribution of small and large fibre neuropathy to erectile dysfunction (ED) in men with type 2 diabetes (T2D). Measures of small and large fibre neuropathy were evaluated in 49 participants with T2D and 20 age-matched controls. ED was present in 59% of participants with T2D. There was no difference in age, duration of diabetes, blood pressure, lipid profile, vibration perception threshold (V) (14.3 ± 7.8 vs 11.2 ± 6.6, P = .429), peroneal (41.4 ± 8.2 vs 44.8 ± 4.4, P = .10) and sural (45.4 ± 5.6 vs 47.1 ± 5.8) nerve conduction velocities (m/s), cold (25.1 ± 3.8 vs 26.2 ± 2.9, P = .815) and warm (43.2 ± 4.0 vs 41.0 ± 3.8) perception thresholds (°C), and deep breathing heart rate variability (18 ± 8 vs 18 ± 8) between participants with and without ED. However, intraepidermal nerve fibre density (no./mm2 ) (4.6 ± 2.8 vs 13.7 ± 2.7, P < .001), corneal nerve fibre density (no./mm2 ) (23.5 ± 6.8 vs 31.3 ± 8.2, P < .001), corneal nerve fibre branch density (no./mm2 ) (55.4 ± 35.3 vs 97.7 ± 46.4, P = .004), corneal nerve fibre length (mm/mm2 ) (17.6 ± 6.8 vs 27.3 ± 6.8, P < .001), and sural (7.7 ± 6.1 vs 14.6 ± 6.7, P = .003) and peroneal (2.5 ± 2.0 vs 4.7 ± 2.0, P = .003) nerve amplitudes were significantly lower in participants with ED compared with those without ED. ED affects almost 2/3 of men with T2D and is associated with small nerve fibre damage but preserved nerve conduction and cardiac autonomic function. Corneal confocal microscopy may serve as a useful non-invasive imaging method to identify small fibre damage in patients with T2D and ED.

Alteration of Inspiratory Muscle Strength is Related to Change in Deep Breathing Heart Rate Variability in Patients Submitted to Open-Heart Surgery

Aim: Despite the reduction of respiratory muscle strength and cardiac autonomic modulation after open-heart surgery has been demonstrated, the association between changes in both variables has not been investigated. This study aimed to determine the correlation between change in inspiratory muscle strength and change in deep breathing heart rate variability in patients submitted to open-heart surgery.Material and Methods: An observational cross-sectional study was conducted among 32 participants aged between 35 and 60 years who were undergoing coronary artery bypass graft and cardiac valve surgery. Inspiratory muscle strength was assessed by measuring maximal inspiratory pressure using a respiratory pressure meter (RPM 01, Micro Medical Ltd., United Kingdom). Deep breathing heart rate variability was collected using a Polar heart rate monitor (Polar Electro Ltd., Finland) during a slow and deep breathing control. Evaluations were performed on the day of admission and discharge.Results: There was statistically significant reduction in maximal inspiratory pressure and deep breathing heart rate variability indices in discharge period (p&amp;lt;0.05). The difference of expiratory/inspiratory ratio and inspiratory-expiratory differences was significantly correlated with the change in maximal inspiratory pressure in both absolute (r=-0.864, p=0.003 and r=-0.841, p=0.004, respectively) and percentages of predicted values (r=-0.868, p=0.003 and r=-0.834, p=0.005, respectively).Conclusion: Inspiratory muscle weakness was related to impair cardiac vagal modulation in patients who had undergone open-heart surgery. The present study could provide rehabilitation targets to improve inspiratory muscle strength and cardiac vagal tone.

Study of cardiac parasympathoautonomic regulation in men of different ages

Objective: Cardiovagal autonomic control is protective physiological mechanism that associates cardiorespiratory fitness. Its evaluation with noninvasive simple means has important role in clinical neurophysiology for application in medical preventive and promotive care. Cardiovagal regulatory function was evaluated among overtly healthy adult male workers of youth to elderly age, using simple noninvasive electrophysiological tests. Methods : Based on specific selection criteria 52 males in 23-67 year age were administered deep breathing induced heart rate variability (HRV) and standing induced heart rate response tests of cardiovagal function. Electrocardiography was sole technical resource with manual observations and calculations. Results: The statistically significant observations were mostly precluded due to limited size of the studied sample .However, increasing age even in studied range indicated progressive decline in cardiovagal control in both deep breathing HRV and standing 30:15 heart rate response tests Conclusion: Declines of small magnitude in cardiovagal regulation at rest in supine posture may prove costly upon exercise situation when sympathetic outflow overtakes cardiovascular function. Exercise training and measures as Yoga that boost vagal tone acquire greater significance in aging adults who may have to occasionally take up physically strenuas tasks.

Quantitative sensory testing in type 1 diabetic patients with mild to severe diabetic neuropathy

Background: Small nerve fibre damage has been shown to precede large fibre damage and represents the early stage for diabetic neuropathy (DPN). Aims: To assess small nerve fibre deficit in patients with mild to severe DPN using quantitative sensory testing (QST) and to correlate QST findings with other neuropathy assessment measures in patients with DPN. Materials and Methods: Seventy-nine diabetic patients (49 with and 30 without diabetic neuropathy) and 35 healthy volunteers underwent neuropathy assessment. The evaluation comprised neuropathy symptoms profile, modified neuropathy disability score (NDS), quantitative sensory testing (QST) in form of cold and warm thresholds, vibration pressure threshold (VPT), nerve conduction studies (NCS), deep breathing heart rate variability (DB-HRV), and Neuropad staining scores. Patients were also stratified by their NDS scores into mild, moderate and severe DPN. Measures of QST were compared among various grades of DPN severity and correlated with other clinical and neurophysiological tests. Results: Patients with DPN demonstrated higher vibration perception (P<0.001) and warm (P<0.001) thresholds and lower cold threshold (P<0.001) and these QST abnormalities related directly to the grade of DPN severity. Measures of QST also correlated with those of nerve conduction studies (r range 0.54-0.68) and autonomic function assessment(r range 0.33-0.48). Conclusion: Quantitative sensory testing can identify small nerve fibres impairment which could represent the early stage of diabetic neuropathy and hence the optimal period for intervention.

Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study

Autonomic and somatic denervation is well established in Parkinson's disease (PD). Objectives(1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. MethodsTwenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease – autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III “ON”] and cumulative Levodopa dose. ResultsPD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. ConclusionCCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD.

Automated Quantification of Neuropad Improves Its Diagnostic Ability in Patients with Diabetic Neuropathy

Neuropad is currently a categorical visual screening test that identifies diabetic patients at risk of foot ulceration. The diagnostic performance of Neuropad was compared between the categorical and continuous (image-analysis (Sudometrics)) outputs to diagnose diabetic peripheral neuropathy (DPN). 110 subjects with type 1 and 2 diabetes underwent assessment with Neuropad, Neuropathy Disability Score (NDS), peroneal motor nerve conduction velocity (PMNCV), sural nerve action potential (SNAP), Deep Breathing-Heart Rate Variability (DB-HRV), intraepidermal nerve fibre density (IENFD), and corneal confocal microscopy (CCM). 46/110 patients had DPN according to the Toronto consensus. The continuous output displayed high sensitivity and specificity for DB-HRV (91%, 83%), CNFD (88%, 78%), and SNAP (88%, 83%), whereas the categorical output showed high sensitivity but low specificity. The optimal cut-off points were 90% for the detection of autonomic dysfunction (DB-HRV) and 80% for small fibre neuropathy (CNFD). The diagnostic efficacy of the continuous Neuropad output for abnormal DB-HRV (AUC: 91%, P = 0.0003) and CNFD (AUC: 82%, P = 0.01) was better than for PMNCV (AUC: 60%). The categorical output showed no significant difference in diagnostic efficacy for these same measures. An image analysis algorithm generating a continuous output (Sudometrics) improved the diagnostic ability of Neuropad, particularly in detecting autonomic and small fibre neuropathy.

Corneal Confocal Microscopy Shows an Improvement in Small-Fiber Neuropathy in Subjects With Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Compared With Multiple Daily Injection

Improved glycemic control is the only treatment that has been shown to be effective for diabetic peripheral neuropathy in patients with type 1 diabetes (1). Continuous subcutaneous insulin infusion (CSII) is superior to multiple daily insulin injection (MDI) for reducing HbA1c and hypoglycemic events (2). Here, we have compared the benefits of CSII compared with MDI for neuropathy over 24 months. A total of 49 subjects with T1DM (18 on CSII vs. 31 on MDI) and 40 age-matched control subjects underwent assessment of vibration perception threshold (VPT), cold threshold (CT), warm threshold (WT), neurophysiology, deep breathing heart rate variability (DB-HRV), intraepidermal nerve fiber density (IENFD), and corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and after 24 months. At baseline, subjects on CSII and MDI were …

Deep Breathing Heart Rate Variability is Associated with Inspiratory Muscle Weakness in Chronic Heart Failure

There is a synchronism between the respiratory and cardiac cycles. However, the relationship of inspiratory muscle weakness in chronic heart failure (CHF) on cardiac autonomic modulation is unknown. The purpose of the present investigation was to evaluate the impact of inspiratory muscle strength on the magnitude of respiratory sinus arrhythmia. Ten CHF (62 ± 7 years--left ventricle eject fraction of 40 ± 5% and New York Heart Association class I-III) and nine matched-age healthy volunteers (64 ± 5 years) participated in this study. Heart rate variability (HRV) was obtained at rest and during deep breathing manoeuvre (DB-M) by electrocardiograph. CHF patients demonstrated impaired cardiac autonomic modulation at rest and during DB-M when compared with healthy subjects (p < 0.05). Moreover, significant and positive correlations between maximal inspiratory pressure and inspiratory-expiratory differences (r = 0.79), expiratory/inspiratory ratio (r = 0.83), root mean square of the successive differences (r = 0.77), standard deviation of NN intervals (r = 0.77), low frequency (r = 0.77), and high frequency (r = 0.70) were found during DB-M. At rest, significant correlations were found also. Patients with CHF presented impaired cardiac autonomic modulation at rest. In addition, cardiac autonomic control of heart rate was associated with inspiratory muscle weakness in CHF. Based on this evidence, recommendations for future research applications of respiratory muscle training can bring to light a potentially valuable target for rehabilitation.

Deep breathing heart rate variability is associated with respiratory muscle weakness in patients with chronic obstructive pulmonary disease

BACKGROUNDA synchronism exists between the respiratory and cardiac cycles. However, the influence of the inspiratory muscle weakness in chronic obstructive pulmonary disease (COPD) on cardiac autonomic control is unknown. The purpose of the present investigation was to evaluate the influence of respiratory muscle strength on autonomic control in these patients.METHODSTen chronic obstructive pulmonary disease patients (69±9 years; FEV1/FVC 59±12% and FEV1 41±11% predicted) and nine age-matched healthy volunteers (64±5 years) participated in this study. Heart-rate variability (HRV) was obtained at rest and during respiratory sinusal arrhythmia maneuver (RSA-M) by electrocardiograph.RESULTSChronic obstructive pulmonary disease patients demonstrated impaired cardiac autonomic modulation at rest and during RSA-M when compared with healthy subjects (p<0.05). Moreover, significant and positive correlations between maximal inspiratory pressure (MIP) and the inspiratory-expiratory difference (ΔIE) (r = 0.60, p<0.01) were found.CONCLUSIONPatients with chronic obstructive pulmonary disease presented impaired sympathetic-vagal balance at rest. In addition, cardiac autonomic control of heart rate was associated with inspiratory muscle weakness in chronic obstructive pulmonary disease. Based on this evidence, future research applications of respiratory muscle training may bring to light a potentially valuable target for rehabilitation.