Nocturnal hypoxemic burden and micro- and macrovascular disease in patients with type 2 diabetes.

BACKGROUND: Micro- and macrovascular diseases are common in patients with type 2 diabetes mellitus (T2D) and may be partly caused by nocturnal hypoxemia. The study aimed to characterize the composition of nocturnal hypoxemic burden and to assess its association with micro- and macrovascular disease in patients with T2D. METHODS: This cross-sectional analysis includes overnight oximetry from 1247 patients with T2D enrolled in the DIACORE (DIAbetes COhoRtE) study. Night-time spent below a peripheral oxygen saturation of 90% (T90) as well as T90 associated with non-specific drifts in oxygen saturation (T90non - specific), T90 associated with acute oxygen desaturation (T90desaturation) and desaturation depths were assessed. Binary logistic regression analyses adjusted for known risk factors (age, sex, smoking status, waist-hip ratio, duration of T2D, HbA1c, pulse pressure, low-density lipoprotein, use of statins, and use of renin-angiotensin-aldosterone system inhibitors) were used to assess the associations of such parameters of hypoxemic burden with chronic kidney disease (CKD) as a manifestation of microvascular disease and a composite of cardiovascular diseases (CVD) reflecting macrovascular disease. RESULTS: Patients with long T90 were significantly more often affected by CKD and CVD than patients with a lower hypoxemic burden (CKD 38% vs. 28%, p < 0.001; CVD 30% vs. 21%, p < 0.001). Continuous T90desaturation and desaturation depth were associated with CKD (adjusted OR 1.01 per unit, 95% CI [1.00; 1.01], p = 0.008 and OR 1.30, 95% CI [1.06; 1.61], p = 0.013, respectively) independently of other known risk factors for CKD. For CVD there was a thresholdeffect, and only severly and very severly increased T90non-specific was associated with CVD ([Q3;Q4] versus [Q1;Q2], adjusted OR 1.51, 95% CI [1.12; 2.05], p = 0.008) independently of other known risk factors for CVD. CONCLUSION: While hypoxemic burden due to oxygen desaturations and the magnitude of desaturation depth were significantly associated with CKD, only severe hypoxemic burden due to non-specific drifts was associated with CVD. Specific types of hypoxemic burden may be related to micro- and macrovascular disease.

A perspective on automated rapid eye movement sleep assessment.

Rapid eye movement sleep is associated with distinct changes in various biomedical signals that can be easily captured during sleep, lending themselves to automated sleep staging using machine learning systems. Here, we provide a perspective on the critical characteristics of biomedical signals associated with rapid eye movement sleep and how they can be exploited for automated sleep assessment. We summarise key historical developments in automated sleep staging systems, having now achieved classification accuracy on par with human expert scorers and their role in the clinical setting. We also discuss rapid eye movement sleep assessment with consumer sleep trackers and its potential for unprecedented sleep assessment on a global scale. We conclude by providing a future outlook of computerised rapid eye movement sleep assessment and the role AI systems may play.

Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d = -0.31), increase in N3 sleep (d = 0.23), and a small-to-moderate decrease in REM sleep (d = -0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d = -0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

Heart Rate Variability for Evaluating Psychological Stress Changes in Healthy Adults: A Scoping Review.

The utility of heart rate variability (HRV) for characterizing psychological stress is primarily impacted by methodological considerations such as study populations, experienced versus induced stress, and method of stress assessment. Here, we review studies on the associations between HRV and psychological stress, examining the nature of stress, ways stress was assessed, and HRV metrics used. The review was performed according to the PRISMA guidelines on select databases. Studies that examined the HRV-stress relationship via repeated measurements and validated psychometric instruments were included (n = 15). Participant numbers and ages ranged between 10 and 403 subjects and 18 and 60 years, respectively. Both experimental (n = 9) and real-life stress (n = 6) have been explored. While RMSSD was the most reported HRV metric (n = 10) significantly associated with stress, other metrics, including LF/HF (n = 7) and HF power (n = 6) were also reported. Various linear and nonlinear HRV metrics have been utilized, with nonlinear metrics used less often. The most frequently used psychometric instrument was the State-Trait Anxiety Inventory (n = 10), though various other instruments have been reported. In conclusion, HRV is a valid measure of the psychological stress response. Standard stress induction and assessment protocols combined with validated HRV measures in different domains will improve the validity of findings.

Utilisation of machine learning to predict surgical candidates for the treatment of childhood upper airway obstruction.

OBJECTIVE: To investigate the effect of adenotonsillectomy on OSAS symptoms based on a data-driven approach and thereby identify criteria that may help avoid unnecessary surgery in children with OSAS. METHODS: In 323 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either early adenotonsillectomy (eAT; N = 165) or a strategy of watchful waiting with supportive care (WWSC; N = 158), the apnea-hypopnea index, heart period pattern dynamics, and thoraco-abdominal asynchrony measurements from overnight polysomnography (PSG) were measured. Using machine learning, all children were classified into one of two different clusters based on those features. The cluster transitions between follow-up and baseline PSG were investigated for each to predict those children who recovered spontaneously, following surgery and those who did not benefit from surgery. RESULTS: The two clusters showed significant differences in OSAS symptoms, where children assigned in cluster A had fewer physiological and neurophysiological symptoms than cluster B. Whilst the majority of children were assigned to cluster A, those children who underwent surgery were more likely to stay in cluster A after seven months. Those children who were in cluster B at baseline PSG were more likely to have their symptoms reversed via surgery. Children who were assigned to cluster B at both baseline and 7 months after surgery had significantly higher end-tidal carbon dioxide at baseline. Children who spontaneously changed from cluster B to A presented highly problematic ratings in behaviour and emotional regulation at baseline. CONCLUSIONS: Data-driven analysis demonstrated that AT helps to reverse and to prevent the worsening of the pathophysiological symptoms in children with OSAS. Multiple pathophysiological markers used with machine learning can capture more comprehensive information on childhood OSAS. Children with mild physiological and neurophysiological symptoms could avoid AT, and children who have UAO symptoms post AT may have sleep-related hypoventilation disease which requires further investigation. Furthermore, the findings may help surgeons more accurately predict children on whom they should perform AT.

Sleep arousal burden is associated with long-term all-cause and cardiovascular mortality in 8001 community-dwelling older men and women.

AIMS: To quantify the arousal burden (AB) across large cohort studies and determine its association with long-term cardiovascular (CV) and overall mortality in men and women. METHODS AND RESULTS: We measured the AB on overnight polysomnograms of 2782 men in the Osteoporotic Fractures in Men Study (MrOS) Sleep study, 424 women in the Study of Osteoporotic Fractures (SOF) and 2221 men and 2574 women in the Sleep Heart Health Study (SHHS). During 11.2 ± 2.1 years of follow-up in MrOS, 665 men died, including 236 CV deaths. During 6.4 ± 1.6 years of follow-up in SOF, 105 women died, including 47 CV deaths. During 10.7 ± 3.1 years of follow-up in SHHS, 987 participants died, including 344 CV deaths. In women, multivariable Cox proportional hazard analysis adjusted for common confounders demonstrated that AB is associated with all-cause mortality [SOF: hazard ratio (HR) 1.58 (1.01-2.42), P = 0.038; SHHS-women: HR 1.21 (1.06-1.42), P = 0.012] and CV mortality [SOF: HR 2.17 (1.04-4.50), P = 0.037; SHHS-women: HR 1.60 (1.12-2.28), P = 0.009]. In men, the association between AB and all-cause mortality [MrOS: HR 1.11 (0.94-1.32), P = 0.261; SHHS-men: HR 1.31 (1.06-1.62), P = 0.011] and CV mortality [MrOS: HR 1.35 (1.02-1.79), P = 0.034; SHHS-men: HR 1.24 (0.86-1.79), P = 0.271] was less clear. CONCLUSIONS: Nocturnal AB is associated with long-term CV and all-cause mortality in women and to a lesser extent in men.

Causality of cortical and cardiovascular activity during cyclic alternating pattern in non-rapid eye movement sleep.

The dynamic interplay between central and autonomic nervous system activities plays a pivotal role in orchestrating sleep. Macrostructural changes such as sleep-stage transitions or phasic, brief cortical events elicit fluctuations in neural outflow to the cardiovascular system, but the causal relationships between cortical and cardiovascular activities underpinning the microstructure of sleep are largely unknown. Here, we investigate cortical-cardiovascular interactions during the cyclic alternating pattern (CAP) of non-rapid eye movement sleep in a diverse set of overnight polysomnograms. We determine the Granger causality in both 507 CAP and 507 matched non-CAP sequences to assess the causal relationships between electroencephalography (EEG) frequency bands and respiratory and cardiovascular variables (heart period, respiratory period, pulse arrival time and pulse wave amplitude) during CAP. We observe a significantly stronger influence of delta activity on vascular variables during CAP sequences where slow, low-amplitude EEG activation phases (A1) dominate than during non-CAP sequences. We also show that rapid, high-amplitude EEG activation phases (A3) provoke a more pronounced change in autonomic activity than A1 and A2 phases. Our analysis provides the first evidence on the causal interplay between cortical and cardiovascular activities during CAP. Granger causality analysis may also be useful for probing the level of decoupling in sleep disorders. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Composition of nocturnal hypoxaemic burden and its prognostic value for cardiovascular mortality in older community-dwelling men.

AIMS: To investigate the composition of nocturnal hypoxaemic burden and its prognostic value for cardiovascular (CV) mortality in community-dwelling older men. METHODS AND RESULTS: We analysed overnight oximetry data from polysomnograms obtained in 2840 men from the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study (ClinicalTrials.gov Identifier: NCT00070681) to determine the number of acute episodic desaturations per hour (oxygen desaturation index, ODI) and time spent below 90% oxygen saturation (T90) attributed to acute desaturations (T90desaturation) and to non-specific drifts in oxygen saturation (T90non-specific), respectively, and their relationship with CV mortality. After 8.8 ± 2.7 years follow-up, 185 men (6.5%) died from CV disease. T90 [hazard ratio (HR) 1.21, P < 0.001], but not ODI (HR 1.13, P = 0.06), was significantly associated with CV death in univariate analysis. T90 remained significant when adjusting for potential confounders (HR 1.16, P = 0.004). Men with T90 > 12 min were at an elevated risk of CV mortality (HR 1.59; P = 0.006). Approximately 20.7 (5.7-48.5) percent of the variation in T90 could be attributed to non-specific drifts in oxygen saturation. T90desaturation and T90non-specific were individually associated with CV death but combining both variables did not improve the prediction. CONCLUSION: In community-dwelling older men, T90 is an independent predictor of CV mortality. T90 is not only a consequence of frank desaturations, but also reflects non-specific drifts in oxygen saturation, both contributing towards the association with CV death. Whether T90 can be used as a risk marker in the clinical setting and whether its reduction may constitute a treatment target warrants further study.

Nocturnal ventricular repolarization lability predicts cardiovascular mortality in the Sleep Heart Health Study.

The objective of the present study was to quantify repolarization lability and its association with sex, sleep stage, and cardiovascular mortality. We analyzed polysomnographic recordings of 2,263 participants enrolled in the Sleep Heart Health Study (SHHS-2). Beat-to-beat QT interval variability (QTV) was quantified for consecutive epochs of 5 min according to the dominant sleep stage [wakefulness, nonrapid eye movement stage 2 (NREM2), nonrapid eye movement stage 3 (NREM3), and rapid eye movement (REM)]. To explore the effect of sleep stage and apnea-hypopnea index (AHI) on QT interval parameters, we used a general linear mixed model and mixed ANOVA. The Cox proportional hazards model was used for cardiovascular disease (CVD) death prediction. Sex-related differences in T wave amplitude ( P < 0.001) resulted in artificial QTV differences. Hence, we corrected QTV parameters by T wave amplitude for further analysis. Sleep stages showed a significant effect ( P < 0.001) on QTV. QTV was decreased in deep sleep compared with wakefulness, was higher in REM than in NREM, and showed a distinct relation to AHI in all sleep stages. The T wave amplitude-corrected QTV index (cQTVi) in REM sleep was predictive of CVD death (hazard ratio: 2.067, 95% confidence interval: 1.105-3.867, P < 0.05) in a proportional hazards model. We demonstrated a significant impact of sleep stages on ventricular repolarization variability. Sex differences in QTV are due to differences in T wave amplitude, which should be corrected for. Independent characteristics of QTV measures to sleep stages and AHI showed different behaviors of heart rate variability and QTV expressed as cQTVi. cQTVi during REM sleep predicts CVD death. NEW & NOTEWORTHY We demonstrate here, for the first time, a significant impact of sleep stages on ventricular repolarization variability, quantified as QT interval variability (QTV). We showed that QTV is increased in rapid eye movement sleep, reflective of high sympathetic drive, and predicts death from cardiovascular disease. Sex-related differences in QTV are shown to be owing to differences in T wave amplitude, which should be corrected for.

Mean nocturnal respiratory rate predicts cardiovascular and all-cause mortality in community-dwelling older men and women.

Respiratory frequency (f R) predicts in-hospital and short-term mortality in patients with a variety of pathophysiological conditions, but its predictive value for long-term cardiovascular and all-cause mortality in the general population is unknown. Here, we investigated the relationship between mean nocturnal f R and mortality in community-dwelling older men and women.We measured mean nocturnal f R during sleep from overnight polysomnography in 2686 men participating in the Osteoporotic Fractures in Men Study (MrOS) Sleep study and 406 women participating in the Study of Osteoporotic Fractures (SOF) to investigate the relationship between mean nocturnal f R and long-term cardiovascular and all-cause mortality.166 (6.1%) men in the MrOS cohort (8.9±2.6 years' follow-up) and 46 (11.2%) women in the SOF cohort (6.4±1.6 years' follow-up) died from cardiovascular disease. All-cause mortality was 51.2% and 26.1% during 13.7±3.7 and 6.4±1.6 years' follow-up in the MrOS Sleep study and the SOF cohorts, respectively. Multivariable Cox regression analysis adjusted for significant covariates demonstrated that f R dichotomised at 16 breaths·min-1 was independently associated with cardiovascular mortality (MrOS: hazard ratio (HR) 1.57, 95% CI 1.14-2.15; p=0.005; SOF: HR 2.58, 95% CI 1.41-4.76; p=0.002) and all-cause mortality (MrOS: HR 1.18, 95% CI 1.04-1.32; p=0.007; SOF: HR 1.50, 95% CI 1.02-2.20; p=0.04).In community-dwelling older men and women, polysomnography-derived mean nocturnal f R ≥16 breaths·min-1 is an independent predictor of long-term cardiovascular and all-cause mortality. Whether nocturnal mean f R can be used as a risk marker warrants further prospective studies.

Role of respiration in the cardiovascular response to orthostatic and mental stress.

The objective of this study was to determine the response of heart rate and blood pressure variability (respiratory sinus arrhythmia, baroreflex sensitivity) to orthostatic and mental stress, focusing on causality and the mediating effect of respiration. Seventy-seven healthy young volunteers (46 women, 31 men) aged 18.4 ± 2.7 yr underwent an experimental protocol comprising supine rest, 45° head-up tilt, recovery, and a mental arithmetic task. Heart rate variability and blood pressure variability were analyzed in the time and frequency domain and modeled as a multivariate autoregressive process where the respiratory volume signal acted as an external driver. During head-up tilt, tidal volume increased while respiratory rate decreased. During mental stress, breathing rate increased and tidal volume was elevated slightly. Respiratory sinus arrhythmia decreased during both interventions. Baroreflex function was preserved during orthostasis but was decreased during mental stress. While sex differences were not observed during baseline conditions, cardiovascular response to orthostatic stress and respiratory response to mental stress was more prominent in men compared with women. The respiratory response to the mental arithmetic tasks was more prominent in men despite a significantly higher subjectively perceived stress level in women. In conclusion, respiration shows a distinct response to orthostatic versus mental stress, mediating cardiovascular variability; it needs to be considered for correct interpretation of heart rate and blood pressure phenomena.

Ascending aortic blood flow velocity is increased in children with primary snoring/mild sleep-disordered breathing and associated with an increase in CD8 + T cells expressing TNFα and IFNγ.

Sleep-disordered breathing (SDB) is associated with cardiovascular disease and systemic inflammation in adults but this remains to be explored in children, especially in children with the most common form of SDB, i.e. primary snoring/mild SDB. This pilot study investigated the relationship between the cardiovascular function and inflammation in children with mild SDB. Nineteen participants aged 5-14 years underwent overnight polysomnography, cardiac magnetic resonance imaging (aortic blood flow velocity and left and right ventricular systolic function) and assessment for inflammatory markers (intracellular cytokine analysis of T cells by flow cytometry). Parents also completed the Sleep Disturbances Scale for Children (SDSC). Children with mild SDB exhibited increased ascending aortic peak systolic velocity compared to controls (SDB 119.95 m/s vs. control 101.49 m/s, p < 0.05). No significant group differences were observed for left and right ventricular ejection fraction or mean aortic blood flow velocity from either the ascending aorta or pulmonary artery. Children with mild SDB had increased inflammatory markers as demonstrated by elevated T cell interferon gamma (IFNγ) (SDB 52 ± 4% vs. control 25 ± 3% positive cells, p < 0.005) and tumour necrosis factor alpha (TNFα) (SDB 39 ± 4% vs. control 20 ± 2% positive cells, p < 0.005) expression from CD8+ cells. A strong positive correlation was observed between ascending aorta peak blood flow velocity and both TNFα and IFNγ (TNFα, r = 0.54, p < 0.03; IFNγ, r = 0.63, p < 0.005, respectively). Polysomnography revealed that oxygen saturation (SaO2) nadir was significantly lower in children with mild SDB compared to controls (SDB 92.3 ± 2.7% vs. control 94.4 ± 1.6%, p < 0.05). A lower SaO2 nadir was associated with an increased ascending aorta peak systolic velocity (r = - 0.48, p < 0.05). As well, both a lower SaO2 nadir and an increased ascending aorta peak systolic velocity were associated with higher SDSC Sleep-Disordered Breathing and Disorder of Initiating and Maintaining Sleep subscale scores but not the polysomnographic-derived Obstructive Apnea-Hypopnea Index. The finding of elevated ascending aortic peak systolic blood flow velocity and its association with increased inflammatory markers suggests that the profile of cardiovascular changes noted in adult SDB may also occur in children with mild SDB.

Adenotonsillectomy for childhood obstructive sleep apnoea reduces thoraco-abdominal asynchrony but spontaneous apnoea-hypopnoea index normalisation does not.

The efficacy of adenotonsillectomy for treating obstructive sleep apnoea syndrome (OSAS) in children has been established, but its precise effects on inspiratory effort are not well documented.In 353 children enrolled in the Childhood Adenotonsillectomy Trial, randomised to undergo either early adenotonsillectomy (n=182) or a strategy of watchful waiting with supportive care (WWSC) (n=171), thoraco-abdominal asynchrony (TAA) was analysed during quiet, non-apnoeic and non-hypopnoeic breathing during sleep at baseline and at 7 months using overnight polysomnography.Children who underwent early adenotonsillectomy demonstrated a reduction in TAA post-surgery while the WWSC arm showed no change. On assessing TAA with regard to normalisation of clinical polysomnography findings at follow-up, TAA was reduced in children who had surgical resolution of OSAS (based on apnoea-hypopnoea index), but not in children who displayed spontaneous normalisation of apnoea-hypopnoea index. In the latter group, TAA was inversely correlated with quality of life.We conclude that adenotonsillectomy reduces TAA during quiet sleep. Monitoring of instantaneous TAA may yield additional insight in the dynamic changes of inspiratory effort. In combination with traditional indices of obstruction, TAA may more accurately characterise the degree of sleep-disordered breathing in children.

An evaluation of multiple algorithms for the measurement of the heart rate corrected JTpeak interval.

Interest in the effects of drugs on the heart rate-corrected JTpeak (JTpc) interval from the body-surface ECG has spawned an increasing number of scientific investigations in the field of regulatory sciences, and more specifically in the context of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. We conducted a novel initiative to evaluate the role of automatic JTpc measurement technologies by comparing their ability to distinguish multi- from single-channel blocking drugs. A set of 5232 ECGs was shared by the FDA (through the Telemetric and Holter ECG Warehouse) with 3 ECG device companies (AMPS, Mortara, and Philips). We evaluated the differences in drug-concentration effects on these measurements between the commercial and the FDA technologies. We provide a description of the drug-induced placebo-corrected changes from baseline for dofetilide, quinidine, ranolazine, and verapamil, and discuss the various differences across all technologies. The results revealed only small differences between measurement technologies evaluated in this study. It also confirms that, in this dataset, the JTpc interval distinguishes between multi- and single-channel (hERG) blocking drugs when evaluating the effects of dofetilide, quinidine, ranolazine, and verapamil. However, in the case of quinidine and dofetilide, we noticed a poor consistency across technologies because of the lack of standard definitions for the location of the peak of the T-wave (T-apex) when the T-wave morphology is abnormal.

Calibrated variability of muscle sympathetic nerve activity during graded head-up tilt in humans and its link with noradrenaline data and cardiovascular rhythms.

Muscle sympathetic nerve activity (MSNA) variability is traditionally computed through a low-pass filtering procedure that requires normalization. We proposed a new beat-to-beat MSNA variability computation that preserves dimensionality typical of an integrated neural discharge (i.e., bursts per unit of time). The calibrated MSNA (cMSNA) variability technique is contrasted with the traditional uncalibrated MSNA (ucMSNA) version. The powers of cMSNA and ucMSNA variabilities in the low-frequency (LF, from 0.04 to 0.15 Hz) band were computed with those of the heart period (HP) of systolic and diastolic arterial pressure (SAP and DAP, respectively) in seven healthy subjects (age, 20-28 years; median, 22 years; 5 women) during a graded head-up tilt. Subjects were sequentially tilted at 0°, 20°, 30°, 40°, and 60° table inclinations. The LF powers of ucMSNA and HP variabilities were expressed in normalized units (LFnu), whereas all remaining spectral markers were expressed in absolute units. We found that 1) the LF power of cMSNA variability was positively correlated with tilt angle, whereas the LFnu power of the ucMSNA series was uncorrelated; 2) the LF power of cMSNA variability was correlated with LF powers of SAP and DAP, LFnu power of HP and noradrenaline concentration, whereas the relationship of the LFnu power of ucMSNA variability to LF powers of SAP and DAP was weaker and that to LFnu power of HP was absent; and 3) the stronger relationship of cMSNA variability to SAP and DAP spectral markers compared with the ucMSNA series was confirmed individually. The cMSNA variability appears to be more suitable in describing sympathetic control in humans than traditional ucMSNA variability.

QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology.

This consensus guideline discusses the electrocardiographic phenomenon of beat-to-beat QT interval variability (QTV) on surface electrocardiograms. The text covers measurement principles, physiological basis, and clinical value of QTV. Technical considerations include QT interval measurement and the relation between QTV and heart rate variability. Research frontiers of QTV include understanding of QTV physiology, systematic evaluation of the link between QTV and direct measures of neural activity, modelling of the QTV dependence on the variability of other physiological variables, distinction between QTV and general T wave shape variability, and assessing of the QTV utility for guiding therapy. Increased QTV appears to be a risk marker of arrhythmic and cardiovascular death. It remains to be established whether it can guide therapy alone or in combination with other risk factors. QT interval variability has a possible role in non-invasive assessment of tonic sympathetic activity.

Slowed atrial and atrioventricular conduction and depressed HRV in a murine model of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common heritable cardiac disorder with diverse clinical outcomes including sudden death, heart failure, and stroke. Depressed heart rate variability (HRV), a measure of cardiac autonomic regulation, has been shown to predict mortality in patients with cardiovascular disease. Cardiac autonomic remodelling in animal models of HCM are not well characterised. This study analysed Gly203Ser cardiac troponin-I transgenic (TG) male mice previously demonstrated to develop hallmarks of HCM by age 21 weeks. 33 mice aged 30 and 50 weeks underwent continuous electrocardiogram (ECG) recording for 30 min under anaesthesia. TG mice demonstrated prolonged P-wave duration (P < 0.001) and PR intervals (P < 0.001) compared to controls. Additionally, TG mice demonstrated depressed standard deviation of RR intervals (SDRR; P < 0.01), coefficient of variation of RR intervals (CVRR; P < 0.001) and standard deviation of heart rate (SDHR; P < 0.001) compared to controls. Additionally, total power was significantly reduced in TG mice (P < 0.05). No significant age-related difference in either strain was observed in ECG or HRV parameters. Mice with HCM developed slowed atrial and atrioventricular conduction and depressed HRV. These changes were conserved with increasing age. This finding may be indicative of atrial and ventricular hypertrophy or dysfunction, and perhaps an indication of worse clinical outcome in heart failure progression in HCM patients.

Measurement of T wave variability in body surface ECG.

Lability in the ventricular repolarization process has been associated with an increased risk of experiencing ventricular tachycardia or fibrillation. A number of risk predictors have been devised that quantify beat-to-beat variability in the T wave morphology of body surface ECG. Initial studies have suggested that measurement of T wave variability may yield important prognostics markers of cardiac mortality, but approaches and experimental designs vary. The aim of this contribution is to provide an overview of existing techniques as well as discuss some of the methodical considerations.