• Bladder cancer
• Distress
• Heart-rate variability
• Inflammation
• Life-satisfaction
• Moderation

• Colorectal cancer
• Complications
• Heart rate variability
• Perioperative period
• Prediction

• autonomic nervous system
• bladder cancer
• heart-rate variability
• immune–inflammatory markers
• stress

• Humans
• Male
• Female
• Urinary Bladder Neoplasms/immunology
• Urinary Bladder Neoplasms/blood
• Middle Aged
• Inflammation/blood
• Inflammation/immunology
• Aged
• Adaptive Immunity
• Heart Rate
• Sympathetic Nervous System/physiopathology
• Receptors, Immunologic/blood
• Membrane Glycoproteins/blood
• Triggering Receptor Expressed on Myeloid Cells-1/blood
• Triggering Receptor Expressed on Myeloid Cells-1/metabolism
• Vagus Nerve/physiopathology
• Biomarkers/blood

• VEGA 1/0090/22 The Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences
• APVV-22-0231 the Slovak Research and Development Agency

• Chinese medicine
• T2DM
• gut microbiome
• gut microbiota
• type 2 diabetes mellitus

• Diabetes Mellitus, Type 2/microbiology
• Diabetes Mellitus, Type 2/therapy
• Gastrointestinal Microbiome/physiology
• Humans
• Medicine, Chinese Traditional/methods
• Drugs, Chinese Herbal/therapeutic use
• Akkermansia
• Acupuncture Therapy/methods
• Bifidobacterium
• Animals

• Autonomic nervous system
• Clinical oncology
• Evaluation methodology
• Heart rate control
• Vagal nerve stimulation

• Autonomic nervous system
• body fat
• breast neoplasms
• exercise
• heart rate

• Humans
• Female
• Breast Neoplasms
• Adiposity
• Longitudinal Studies
• Cancer Survivors
• Obesity
• Exercise/physiology
• Heart Rate/physiology
• Syndactyly

• cancer
• oncology
• psycho-oncology
• psychosocial issues
• quality of life
• sarcoma
• unmet needs

• Humans
• Quality of Life/psychology
• Depression/psychology
• Sarcoma/therapy
• Mental Health
• Soft Tissue Neoplasms

• Nonpharmacological intervention
• Prevention
• Traditional Chinese medicine
• Type 2 diabetes

• FDCT 00712020/ALC Fundo para o Desenvolvimento das Ciências e da Tecnologia
• GUIKEAA22096029 Guangxi Science and Technology Major Project
• AM2022022 Macao Young Scholars Program
• CPG2023-00028-ICMS University of Macau

• cancer
• immunotherapy
• inflammation
• regenerative rehabilitation
• vagus nerve stimulation

• Humans
• Aged
• Vagus Nerve Stimulation/adverse effects
• Quality of Life
• Neoplasms/therapy
• Immunotherapy/adverse effects
• Peripheral Nervous System Diseases

• Autonomic nervous system
• Birth
• Knowledge gap
• Newborn
• Umbilical cord

• surgical oncology
• prognostic markers
• cancer
• colorectal cancer

• Humans
• Heart Rate/physiology
• Reproducibility of Results
• Inflammation
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/surgery
• Morbidity

• 25813 Cancer Research UK
• Chief Scientist Office

• autonomic nervous system
• deep-learning segmentation of vagus nerve
• image processing
• microCT
• neural network
• segmentation
• vagus nerve

• Baroreflex
• Healthy volunteers
• Heart rate variability
• Vagus nerve stimulation

• Breast cancer survivors
• Cardiotoxicity
• HIT
• Physical effects
• Psychosocial effects
• Remote and supervised exercise
• Strength training

• DIN2018- 010129 Industrial Doctorate Spanish National grant program, part of the Strategic Plan on Science and Innovation Support of the Spanish Ministry of Science, Innovation and Universities.
• Industrial Doctorate Spanish National grant program, part of the Strategic Plan on Science and Innovation Support of the Spanish Ministry of Science, Innovation and Universities.

• asystole
• autonomic nervous system
• cord clamping
• hypovolemia

• c reactive protein (CRP)
• cellular senescence
• inflammation
• prefrontal cortex-autonomic nervous system-spleen axis
• telomere length
• the neuro-immuno-senescence integrative model
• vagal neuroimmunomodulation
• vagal tone

• autonomic nervous system
• heart rate variability (HRV)
• ovarian cancer
• parasympathetic activity
• prognostic factor and survival
• vagus nerve

The vagus or “wandering” nerve is the main branch of the parasympathetic nervous system (PNS), innervating most internal organs crucial for health. Activity of the vagus nerve can be non-invasively indexed by heart-rate variability parameters (HRV). Specific HRV parameters predict less all-cause mortality, lower risk of and better prognosis after myocardial infarctions, and better survival in cancer. A non-invasive manner for self-activating the vagus is achieved by performing a slow-paced breathing technique while receiving visual feedback of one’s HRV, called HRV-biofeedback (HRV-B). This article narratively reviews the biological mechanisms underlying the role of vagal activity and vagally mediated HRV in hypertension, diabetes, coronary heart disease (CHD), cancer, pain, and dementia. After searching the literature for HRV-B intervention studies in each condition, we report the effects of HRV-B on clinical outcomes in these health conditions, while evaluating the methodological quality of these studies. Generally, the levels of evidence for the benefits of HRV-B is high in CHD, pain, and hypertension, moderate in cancer, and poor in diabetes and dementia. Limitations and future research directions are discussed.

Evidence suggests that the risk of recurrence and death in patients with early cervical cancer (ECC) undergoing minimally invasive surgery is significantly higher than that in patients undergoing open surgery. However, the mechanisms underlying such a difference remain unclear. Heart rate variability (HRV) represents autonomic nerve activity, which is related to tumorgenesis and can be used as a prognostic indicator for various cancers. The main purpose of this study was to explore the difference in the effects of laparoscopic and open surgery on HRV in ECC patients.

A total of 68 ECC (FIGO IA1 with lymphovascular space invasion -IIA2) patients undergoing radical hysterectomy for the first time (84% open group vs. 16% laparoscopic group) were included. A single-lead micro-ECG recorder was used to collect 5 min electrocardiograms 1 day before the operation and 3 days after the operation, and then HRV time domain and frequency domain indices were analyzed, including mean heart rate (MeanHR), maximum heart rate (MaxHR), minimum heart rate (MinHR), the standard deviation of all normal-to-normal intervals (SDNN), the root mean square of successive interval differences (RMSSD), very low-frequency power (VLF), low-frequency power (LF), high-frequency power (HF), total power (TP), and the ratio of LF to HF (LF/HF).

Heart rate (i.e., MeanHR, MaxHR, and MinHR) were significantly higher, and HRV (i.e., SDNN, RMSSD, LF, HF, and TP) were significantly lower after the operation than before the operation in both the laparoscopic and open groups (P < 0.05). The postoperative reduction in RMSSD and HF was significantly higher in the laparoscopic group than in the open group (P < 0.05).

These data suggest that radical hysterectomy can lead to increased heart rate and decreased HRV in patients with ECC, which can negatively affect cardiac autonomic regulation. Compared with open surgery, laparoscopic surgery has a greater negative impact on the HRV of ECC patients.

• autonomic nerve
• early cervical cancer
• heart rate variability
• laparoscopic surgery
• open surgery

• Meath Foundation

Transcutaneous auricular vagus nerve stimulation (taVNS) has shown positive effects on a variety of diseases. Considering that decreased heart rate variability (HRV) is closely associated with morbidity and mortality for a variety of diseases, it is important to investigate the effect of taVNS on HRV. In Study 1, we conducted a two-stage cross-over trial to compare the effects of taVNS and sham taVNS (staVNS) on HRV. In Study 2, we systematically tested the effects of different taVNS parameters on high frequency (HF) component of HRV. The results showed that taVNS significantly increased measurements of root mean square of the difference between successive RR intervals (RMSSD), percentage of number of pairs of adjacent RR intervals differing greater than 50ms (pRR50), standard deviation of all RR intervals (SDRR), HF. Significantly, enhancement of HF and pRR50 persisted into recovery period. In addition, higher baseline LF/HF ratio was associated with greater LF/HF ratio decrease. Findings also showed that there was no significant difference in measurements of HF between different taVNS parameters. These studies suggest that taVNS could increase HRV, it may help taVNS in the treatment of low HRV related diseases. However, taVNS may not have parameter-specific effects on HRV.

• Adult
• Cross-Over Studies
• Female
• Healthy Volunteers
• Heart/physiology
• Heart Rate
• Humans
• Male
• Transcutaneous Electric Nerve Stimulation/methods
• Vagus Nerve Stimulation/methods
• Young Adult

The aim of this prospective study was to evaluate the association between heart rate variability (HRV) and overall survival of lung cancer patients with brain metastases (LCBM).

Fifty-six LCBM patients were enrolled in this study. Five-minute electrocardiograms were collected before the time to first brain radiotherapy. HRV was analyzed quantitatively by using the time domain parameters, i.e., the standard deviation of all normal-normal intervals (SDNN) and the root mean square of successive differences (RMSSD). Survival time for LCBM patients was defined as from the date of HRV testing to the date of death or the last follow-up.

In the univariate analysis, SDNN ≤ 13 ms (P = 0.003) and RMSSD ≤ 4.8 ms (P = 0.014) significantly predicted poor survival. Multivariate analysis confirmed that RMSSD ≤ 4.8 ms (P = 0.013, hazard ratio = 3.457, 95% confidence interval = 1.303–9.171) was also an independent negative prognostic factor after adjusting for mean heart rate, Karnofsky performance status, and number of brain metastases in LCBM patients.

Decreased RMSSD is independently associated with shorter survival time in LCBM patients. HRV might be a novel predictive biomarker for LCBM prognosis.

Most cancer patients exhibit autonomic dysfunction with attenuated heart rate variability (HRV) levels compared to healthy controls. This research aimed to create and evaluate a machine learning (ML) model enabling discrimination between cancer patients and healthy controls based on 5-min-ECG recordings. We selected 12 HRV features based on previous research and compared the results between cancer patients and healthy individuals using Wilcoxon sum-rank test. Recursive Feature Elimination (RFE) identified the top five features, averaged over 5 min and employed them as input to three different ML. Next, we created an ensemble model based on a stacking method that aggregated the predictions from all three base classifiers. All HRV features were significantly different between the two groups. SDNN, RMSSD, pNN50%, HRV triangular index, and SD1 were selected by RFE and used as an input to three different ML. All three base-classifiers performed above chance level, RF being the most efficient with a testing accuracy of 83%. The ensemble model showed a classification accuracy of 86% and an AUC of 0.95. The results obtained by ML algorithms suggest HRV parameters could be a reliable input for differentiating between cancer patients and healthy controls. Results should be interpreted in light of some limitations that call for replication studies with larger sample sizes.

Outcomes and prognostic factors among patients with brain metastases (BM) have been widely studied, but seldom for the non-elderly. Heart rate variability (HRV) is a physiological phenomenon and has been shown as a survival prognostic factor in cancer patients. This study aimed to evaluate the outcomes and prognosis among non-elderly BM patients with the incorporation of HRV analysis. Forty non-elderly BM patients treated using whole brain radiotherapy (WBRT) were studied from January 2010 prospectively with 5-min electrocardiography (ECG) recordings. Individualized HRV was generated by the ECG, and the time domain HRV index SDNN was chosen for survival analysis. The median overall survival (OS) for the entire group was 6.21 months. Univariate analysis revealed that a KPS < 80 (p = 0.019) and an SDNN < 10 ms (p = 0.007) demonstrated statistical significance for OS; multivariate analysis confirmed that a KPS < 80 (p = 0.004; HR = 3.060, CI = 1.437–6.517) and an SDNN < 10 ms (p = 0.010; HR = 2.664, CI = 1.262–5.624) were independent prognostic factors. Prospective studies for risk stratification among non-elderly BM patients based on our results are warranted to validate our findings.

• age
• brain metastases
• heart rate variability
• non-elderly
• prognosis
• radiotherapy

Cardiac autonomic modulation, assessed by heart rate variability (HRV), is associated with tumor pathogenesis and development as well as invasion and metastasis. This study aimed to examine this association in breast cancer (BC) patients. A total of 133 patients (average age 49.2years) with BC or benign breast tumors were divided into three groups: benign group, early-stage group, and advanced-stage group. About 5-min resting ECG was collected for the analysis of linear and nonlinear HRV parameters. Multiple logistic regression models were performed to test the independent contribution of HRV to breast tumor stage. The advanced-stage group had significantly reduced HRV compared to the benign and early-stage groups. In particular, for each 1-SD increase in SD2, SD of normal-to-normal intervals, very-low frequency, total power, and low frequency, the odds of having advanced staging decreased by 69.3, 64.3, 58.3, 53.3, and 65.9%, respectively. These associations were independent of age, body mass index, mean heart rate (HR), and respiratory rate (RR). These findings suggest an association between HRV and breast tumor stage, and HRV parameters may help construct an effective early diagnostic and clinical prognostic model.

• autonomic modulation
• breast tumors
• heart rate variability
• nonlinear dynamics
• tumor-node-metastasis stages

Background: Cancer therapies have increased patient survival rates, but side effects such as cardiotoxicity and neurotoxicity can lead to autonomic nervous and cardiovascular system dysfunction. This would result in a decrease in parasympathetic activity and the enhancement of sympathetic activity. Heart rate variability (HRV), which reflects autonomic modulation, is a valuable physiological tool since it correlates with cancer-related fatigue, stress, depression, and mortality in patients with cancer.

Objective: This study aimed to analyze the effects of exercise programs on the autonomic modulation, measured by the HRV of patients with cancer and its survivors.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the quality of the articles was assessed with the Physiotherapy Evidence Database (PEDro) scale. The meta-analysis statistic procedure was performed by using RevMan software version 5.3.

Results: From the 252 articles found, six studies were included in the review involving 272 participants aged 30–75 years. Exercise programs had a mean length of 10.4 ± 4.6 weeks, a frequency of 3 ± 1.4 days/week, and a mean duration of 78 ± 23.9 min. In time-domain HRV measures, exercise may increase in the SD of normal-to-normal intervals [p < 0.00001, with a mean difference (MD) of 12.79 ms from 9.03 to 16.55] and a decreased root mean square of successive R–R interval differences (p = 0.002, with an MD of 13.08 ms from 4.90 to 21.27) in comparison with control groups (CG). The frequency-domain data reveal that the exercise group (EG) improve significantly more than the CGs in low frequency [absolute power: p < 0.0001, with a standardized mean difference (SMD) of 0.97 from 0.61 to 1.34; relative power: p = 0.04, with an MD = −7.70 from −15.4 to −0.36], high-frequency [absolute power: p = 0.001, with a SMD of 1.49 from 0.32 to 2.66; relative power: p = 0.04, with an MD of 8.00 normalized units (n.u.) from 0.20 to 15.80], and low-to-high frequency ratio (p = 0.007 with an MD of −0.32 from −0.55 to −0.09).

Conclusion: Exercise programs could lead to positive effects on the autonomic modulation of patients with cancer and its survivors. More beneficial changes may occur with resistance and endurance workouts. However, due to the low number of interventions performed, further research is needed to substantiate the findings and to provide additional insights regarding the exercise intensity required to increase the autonomic modulation of the patient.

• autonomic modulation
• cardiovascular dysfunction
• exercise programs
• heart rate variability
• oncology

• Autonomic function
• Chronic disease
• Heart rate variability biofeedback
• Non-pharmacological intervention
• Symptom management

• Adult
• Anxiety
• Asthma/therapy
• Biofeedback, Psychology
• Heart Rate
• Humans
• Quality of Life

The purpose of this study was to investigate the relationship between heart rate variability (HRV), a non-invasive tool for evaluating autonomic function, and routine coagulation indices (RCIs) in patients with breast cancer (BC). Forty-six BC patients were enrolled in this study. Blood biochemistry tests were performed to extract RCIs, including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). Five-minute electrocardiograms were collected for analysis of HRV parameters (SDNN, RMSSD, LF, HF, LF n.u., HF n.u., LF/HF). Multiple linear regression models examined the relationship of HRV parameters with RCIs. RMSSD, LF n.u., HF n.u., LF/HF were significantly associated with PT. Specifically, the value of PT increased by 0.192 ± 0.091 or 0.231 ± 0.088 s, respectively for each 1 standard deviation (SD) increase in RMSSD or HF n.u.; it increased by 0.230 ± 0.088 or 0.215 ± 0.088 s, respectively for each 1 − SD decrease in LF n.u. or ln (LF/HF) (all P < 0.05). RMSSD was significantly associated with APTT, i.e., the value of APTT increased by 1.032 ± 0.470 s for each 1 − SD increase in RMSSD (P < 0.05). HRV parameters were associated with RCIs in patients with BC. These observations suggest that the autonomic nervous system and coagulation indices in BC patients are linked, potentially explaining the reason that they are both associated with the prognosis.

• Autonomic
• Cancer
• Coherence
• Fatigue
• Sleep
• Survivorship

Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer.

Retrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN <20ms or RMSSD <19ms) and normal HRV (SDNN ≥20ms or RMSSD ≥19ms). Primary endpoints were overall and cancer free survival.

A total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN <20ms vs SDNN ≥20ms:24.4% vs 22.8%, adjusted HR = 0.952 (0.607–1.493), p = 0.829; RMSSD <19ms vs RMSSD ≥19ms:27.0% vs 19.5%, adjusted HR = 1.321 (0.802–2.178), p = 0.274) or cancer recurrence (SDNN <20ms vs ≥20ms:20.1% vs 18.7%, adjusted HR = 0.976 (0.599–1.592), p = 0.924; RMSSD <19ms vs ≥19ms, 21.5% vs 16.9%, adjusted HR = 1.192 (0.706–2.011), p = 0.511). There was no significant association between HRV and CEA-level at one year follow-up, or between HRV and occurrence of a post-operative complication or the severity of post-operative complications.

Heart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV.

• heart rate variability (HRV)
• low-frequency electro-acupuncture
• mid-frequency electro-acupuncture
• vagal tone (HF)

• prognostic markers
• translational research

• Aged
• Antigens, Tumor-Associated, Carbohydrate/blood
• Biomarkers, Tumor/blood
• Carcinoembryonic Antigen/blood
• Electrocardiography
• Female
• Fibrinogen/metabolism
• Heart/physiopathology
• Heart Rate
• Humans
• Male
• Middle Aged
• Nonlinear Dynamics
• Pilot Projects
• Prognosis
• Rest
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/physiopathology
• Trauma Severity Indices

• Anhui Department of Education (Department of Education of Anhui Province)
• National Natural Science Foundation of China (National Science Foundation of China)

• animal research
• auricular vagus nerve
• biophysics
• brain plasticity
• clinical studies
• inflammation
• nerve stimulation

• short-term heart rate variability
• quality of life
• brief behavioral therapy
• breast neoplasms
• multicenter study
• randomized controlled trial

• Adult
• Aged
• Antineoplastic Agents/therapeutic use
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Breast Neoplasms/psychology
• Cognitive Behavioral Therapy
• Female
• Heart Rate
• Humans
• Middle Aged
• Polysomnography
• Quality of Life
• Sleep/physiology
• Sleep Initiation and Maintenance Disorders/psychology
• Sleep Initiation and Maintenance Disorders/therapy
• Time Factors

• R01 CA181659 NCI NIH HHS
• R21 CA185678 NCI NIH HHS
• UG1 CA189961 NCI NIH HHS
• U10 CA037420 NCI NIH HHS
• K07 CA168886 NCI NIH HHS
• R01 CA172145 NCI NIH HHS

• pancreatic cancer
• vagotomy
• cholinergic signaling
• muscarinic receptor
• cancer stem cells

• Animals
• Carcinoma, Pancreatic Ductal/metabolism
• Carcinoma, Pancreatic Ductal/pathology
• Carcinoma, Pancreatic Ductal/prevention & control
• Cell Transformation, Neoplastic/drug effects
• Cell Transformation, Neoplastic/metabolism
• Cell Transformation, Neoplastic/pathology
• Cholinergic Agents/pharmacology
• Genes, ras
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Inbred NOD
• Mice, Knockout
• Mice, SCID
• Neoplastic Stem Cells/drug effects
• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/prevention & control
• Receptor, Muscarinic M1/physiology
• Signal Transduction

• R35 CA210088 NCI NIH HHS
• T32 CA203703 NCI NIH HHS

• global burden of diseases
• neuroimmunology
• neuromodulation
• prediction
• prevention
• vagal nerve

• NFkB
• cellular senescence
• cytokines
• heart rate variability
• parasympathetic activity
• reactive oxygen species
• telomere damage
• the neuro-immuno-senescence integrative model

• HRV
• malignancy
• prognosis
• tumor
• vagal nerve