Deviation Of Normal RR Intervals Research Articles

325-OR: Early Parallel Progression of Peripheral and Cardiac Autonomic Nerve Dysfunction in Recent-Onset Type 1 Diabetes Patients

We previously demonstrated an early parallel involvement of small and large fibers in recent-onset type 2 diabetes. Here we hypothesized that this pattern may also be pertinent to type 1 diabetes (T1D). Therefore, motor and sensory nerve conduction velocity (MNCV, SNCV), vibration perception thresholds (VPT), thermal detection thresholds (TDT), intraepidermal nerve fiber density (IENFD), and heart rate variability (HRV) were assessed in participants with T1D from the German Diabetes Study (GDS) at baseline (diabetes duration ≤1 year) and in glucose-tolerant controls: CON/T1D-B: n=96/360; age [median (1st; 3rd quartile)]: 34.5 (26.0; 46.8)/34.6 (26.5; 45.3) years; male: 72/58%; BMI: 25.0 (22.9; 28.3)/24.0 (22.0 (22.0; 27.0) kg/m²; diabetes duration: -/173 (114; 173) days; HbA1c: 5.1 (5.0; 5.3)/6.4 (5.9; 7.2)%; M-value (hyperinsulinemic-euglycemic clamp): 11.6 (9.1; 13.6)/8.2 (6.5; 10.4) mg*kg-1*min-1. T1D-B showed lower peroneal MNCV ([mean±SEM]: 45.8±0.2 vs. 47.0±0.3 m/s), median MNCV (55.1±0.2 vs. 56.0±0.7 m/s), and IENFD (10.0±0.5 vs. 11.2±0.5 fibers/mm) than CON (P<0.05). In T1D, a deterioration from baseline to 5 years (n=151) was noted for ulnar and median MNCVs and SNCVs (e.g., ulnar MNCV: 57.4±0.4 vs. 56.3±0.3 m/s), malleolar VPT (0.76±0.07 vs. 1.12±0.12 µm), and HRV indices (e.g., standard deviation of normal RR intervals (SDNN): 69.3±2.4 vs. 62.0±2.1 ms; root mean square of successive differences (RMSSD): 42.8±2.3 vs. 34.7±2.0 ms) (all P<0.05). Peroneal MNCV, sural SNCV, and TDT remained unchanged. The decline in MNCV was associated with an increase in HbA1c (e.g., median nerve: β=-0.316, P=0.004) and the deterioration in HRV with decreasing M-value (e.g., SDNN: β=0.246, P=0.041). In conclusion, within the first 5-6 years of type 1 diabetes despite good glycemic control, the deterioration in median and ulnar MNCV was related to worsening HbA1c levels, while cardiac autonomic dysfunction progressed in relation to increasing insulin resistance. Disclosure G.J. Bönhof: None. A. Strom: None. O.P. Zaharia: None. J. Szendroedi: None. K. Muessig: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc. D. Ziegler: Advisory Panel; Self; Allergan, TrigoCare. Consultant; Self; Mitsubishi Tanabe Pharma Corporation, Mylan, Novartis Pharmaceuticals Corporation, Wörwag. Speaker's Bureau; Self; Berlin-Chemie AG. Funding German Ministry of Culture and Science of the State of North Rhine-Westphalia; German Federal Ministry of Health; German Federal Ministry of Education and Research

TREINAMENTO COMBINADO DE SPRINTS E AGACHAMENTO MELHORA A MODULAÇÃO AUTONÔMICA CARDÍACA DE JOVENS SAUDÁVEIS

Studies demonstrate beneficial effects of physical training on cardiac autonomic modulation. Combined training, characterized by different stimulus in the same session, has been widely used because of its performance benefits. The aim of the study was to evaluate the cardiac autonomic modulation through heart rate variability (HRV) of young men after a combined training. 38 healthy young men performed six weeks of combined training of sprints and squats. HRV was measured during rest at the beginning and the end of the full training. The indexes RMSSD (root-mean square of successive differences) and SDNN (standard deviation of normal RR intervals) showed significant increase after the training (p=0.016; ES=0.410; p≤0.001; ES=0.647, respectively). Therefore, it is concluded that the combined training during six weeks was effective to improve cardiac autonomic modulation, evaluated through HRV.

The association between heart rhythm complexity and the severity of abdominal aorta calcification in peritoneal dialysis patients

Abdominal aorta calcification (AAC) has been associated with clinical outcomes in peritoneal dialysis (PD) patients. Heart rhythm complexity analysis has been shown to be a promising tool to predict outcomes in patients with cardiovascular disease. In this study, we aimed to analyze the association between heart rhythm complexity and AAC in PD patients. We prospectively analyzed 133 PD patients. Heart rhythm complexity including detrended fluctuation analysis and multiscale entropy was performed. In linear analysis, the patients in the higher AAC group (AAC ≥15%) had a significantly lower standard deviation of normal RR intervals, very low frequency, low frequency, high frequency and low/high frequency ratio. In non-linear analysis, DFAα1, slope 1–5, scale 5 and area 6–20 were significantly lower in the patients with higher AAC. Receiver operating characteristic curve analysis showed that DFAα1 had the greatest discriminatory power to differentiate these two groups. Multivariate logistic regression analysis showed that DFAα1 and HbA1c were significantly associated with higher AAC ratio. Adding DFAα1 significantly improved the discriminatory power of the linear parameters in both net reclassification improvement and integrated discrimination improvement models. In conclusion, DFAα1 is highly associated with AAC and a potential cardiovascular marker in PD patients.

Cardiovascular Autonomic Neuropathy and Uric Acid in Subjects with Type 1 Diabetes—Preventing Early Renal Loss (PERL) in Type 1 Diabetes Trial

Elevated serum uric acid (SUA), an established risk factor for diabetic nephropathy (DN) may also be a risk factor for cardiovascular autonomic neuropathy (CAN). We evaluated the cross-sectional association between CAN and SUA levels in subjects with type 1 diabetes (T1D), mild to moderate chronic kidney disease (CKD) and a SUA ≥4.5 mg/dl enrolled in the ongoing PERL trial that is evaluating the effect of SUA lowering by allopurinol on kidney function decline, specifically iohexol plasma disappearance glomerular filtration rate (iGFR). Also measured are estimated GFR (eGFR) and albumin excretion rates (AER). Measures of baseline CAN included resting heart rate, standard deviation of normal RR interval (SDNN), and QTi (Bazzett formula) derived from resting ECG recordings (RR interval extracted from digital ECG images by ECGSCAN software). Four hundred ninety seven PERL participants had valid baseline CAN and renal function data (age 51 ± 11 years, 68% male, T1D duration 35 ± 12 years, HbA1c 8±1%). Subjects in the highest tertile of serum UA levels had worse measures of renal function (iGFR 60 ± 16 vs. 74 ± 60 ml/min/1.73 m2, eGFR 65.7 ± 18.1 vs. 82.7 ± 17.2 ml/min/1.73 m2, AER 370 ± 783 vs. 1181 ± 475 mcg/mg creatinine) compared to those in the lowest tertile. SDNN correlated negatively with SUA levels (r = -0.11, P = 0.0093). In a multiple linear regression model, lower SDNN was associated with higher SUA levels independent of age, gender, BMI, blood pressure, and HbA1c (β = -0.061, SE= 0.021, P = 0.0049), but this association was no longer significant when adjusted for iGFR (β = -0.0184, SE= 0.024, P = 0.46). In summary, elevated SUA was significantly associated with CAN in subjects with T1D independent of some traditional cardiovascular risk factors. This relationship operated, at least in part, through the inverse association of SUA levels with renal function. Disclosure M. Jaiswal: None. A. Doria: Research Support; Self; Sanofi-Aventis. M. Mauer: None. R. Pop-Busui: Research Support; Self; AstraZeneca.

Heart rate variability analysis in patients with multiple sclerosis

BackgroundMultiple sclerosis can cause cardiovascular autonomic dysfunction. It is assumed that is caused by multiple demyelinating plaques localized in the brain stem and spinal cord. Previous studies have determined this using tilt table test, heart rate responses to Valsalva maneuver and deep breathing and heart rate variability analysis with 24 h Holter monitoring. However there is not a consensus regarding the presence of the relationship between autonomic dysfunction and severity of multiple sclerosis, type of multiple sclerosis and expanded disability status scale.The aim of the study is comparison of heart rate variability between recently diagnosed patients with relapsing-remitting multiple sclerosis and healthy controls by using 24 h Holter monitoring. Also we intended to investigate relationship between Expanded Disability Status Scale score, Multiple Sclerosis Functional Composite scores and cranial and spinal magnetic resonance imaging findings and hearth rate variability. MethodFifty-one patients with newly diagnosed relapsing-remitting multiple sclerosis and 44 age- and sex-matched healthy controls were compared in this study. Patients with multiple sclerosis, who were already under immunomodulatory or immunosuppressive treatment, were excluded from the study. Echocardiography and hearth rate variability analysis using 24 h period Holter monitoring were performed in all of the subjects. Echocardiography was used to detect the presence of cardiac pathology. One multiple sclerosis patient with right ventricular dilatation and mobile intratrial septum was excluded from the study. All the patients underwent cranial and cervical spinal magnetic resonance imaging to determine the relationship between autonomic abnormalities and magnetic resonance imaging. ResultsOur results showed that hearth rate variability values were significantly lower in patients with multiple sclerosis when compared with healthy controls: SDNN index (the mean of all the 5 min standard deviations of normal RR intervals during the 24 h period) (59.80 ± 17.33 vs. 67.20 ± 21.28, p = 0,044), the root-mean-square successive difference (rMSSD) (34.40 ± 17.50 vs. 38.25 ± 12.95, p = 0,042), spectral hearth rat variability total power (3738.84 ± 2085.51 vs. 4427.44 ± 1965.71, p = 0,037), spectral hearth rate variability low frequency (852.03 ± 450.54 vs. 1011.75 ± 370.06, p = 0,018). Ten patients (20%) had brainstem lesion, 25 patients (50%) had cervical lesions and 10 patients (20%) had thoracic spinal lesions on magnetic resonance imaging. There was no significant relationship between location of the lesions and heart rate variability analyses. Also there was no significant relationship between hearth rate variability values and Expanded Disability Status Scale score, Multiple Sclerosis Functional Composite scores or number of multiple sclerosis attack (p > 0,05). ConclusionThese findings reveals that our study population with multiple sclerosis had decreased heart rate variability compared to healthy controls. This was reflected by dysfunction of both parasympathetic and sympathetic parameters of hearth rate variability analysis. However, there is no significant relationship between hearth rate variability analysis and the findings on cranial, cervical, thoracic spinal magnetic resonance imaging findings, number of attack, Expanded Disability Status Scale score or Multiple Sclerosis Functional Composite scores in patients with multiple sclerosis.

Combinatorial effect of nicotine and black tea on heart rate variability: Useful or harmful?

The effect of nicotine on heart rate variability (HRV) is controversial. Autonomic nervous system is the main regulator of heart rhythm, and heart rate variability is an appropriate index to assessment of the effects of the autonomic system on heart. In this study, the combination effect of nicotine and black tea consumption on sympatho-vagal balance and heart rate variability was investigated in rats. Male Wistar rats were randomized into four groups as control, tea (2.5g/100cc, daily), nicotine (2mg/kg/d) and tea plus nicotine groups which treated for 28days, and in the 29th day, their electrocardiograms (lead II) were recorded. The mean of high-frequency power (HF) in tea, nicotine and tea plus nicotine groups was significantly more than control group (P<.05), and low-frequency power/high-frequency power (LF/HF) ratio in the nicotine and tea+nicotine groups was significantly less than control group (P<.05). LF values did not differ significantly among groups. Mean of standard deviation of normal RR intervals (SDNN) and square root of the mean squared differences of successive RR intervals (RMSSD) increased significantly in tea, nicotine and tea+nicotine groups in comparison with control group (P<.05) Overall, 4-week administration of black tea, nicotine or their combination with dosages used in this study can increase the heart rate variability and improve the sympatho-vagal balance in rat.

Heart rhythm complexity impairment in patients undergoing peritoneal dialysis.

Cardiovascular disease is one of the leading causes of death in patients with advanced renal disease. The objective of this study was to investigate impairments in heart rhythm complexity in patients with end-stage renal disease. We prospectively analyzed 65 patients undergoing peritoneal dialysis (PD) without prior cardiovascular disease and 72 individuals with normal renal function as the control group. Heart rhythm analysis including complexity analysis by including detrended fractal analysis (DFA) and multiscale entropy (MSE) were performed. In linear analysis, the PD patients had a significantly lower standard deviation of normal RR intervals (SDRR) and percentage of absolute differences in normal RR intervals greater than 20 ms (pNN20). Of the nonlinear analysis indicators, scale 5, area under the MSE curve for scale 1 to 5 (area 1–5) and 6 to 20 (area 6–20) were significantly lower than those in the control group. In DFA anaylsis, both DFA α1 and DFA α2 were comparable in both groups. In receiver operating characteristic curve analysis, scale 5 had the greatest discriminatory power for two groups. In both net reclassification improvement model and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of SDRR, pNN20, and pNN50. In conclusion, PD patients had worse cardiac complexity parameters. MSE parameters are useful to discriminate PD patients from patients with normal renal function.

Activation of N-methyl-d-aspartate receptors reduces heart rate variability and facilitates atrial fibrillation in rats.

The goal of this study was to assess the effects of N-methyl-d-aspartate (NMDA) receptors activation on heart rate variability (HRV) and susceptibility to atrial fibrillation (AF). Rats were randomized for treatment with saline, NMDA (agonist of NMDA receptors), or NMDA plus MK-801 (antagonist of NMDA receptors) for 2 weeks. Heart rate variability was evaluated by using implantable electrocardiogram telemeters. Atrial fibrillation susceptibility was assessed with programmed stimulation in isolated hearts. Compared with the controls, the NMDA-treated rats displayed a decrease in the standard deviation of normal RR intervals, the standard deviation of the average RR intervals, the mean of the 5-min standard deviations of RR intervals, the root mean square of successive differences, and high frequency (HF); and an increase in low frequency (LF) and LF/HF (all P< 0.01). Additionally, the NMDA-treated rats showed prolonged activation latency and reduced effective refractory period (all P< 0.01). Importantly, AF was induced in all NMDA-treated rats. While atrial fibrosis developed, connexin40 downgraded and metalloproteinase 9 upgraded in the NMDA-treated rats (all P< 0.01). Most of the above alterations were mitigated by co-administering with MK-801. These results indicate that NMDA receptors activation reduces HRV and enhances AF inducibility, with cardiac autonomic imbalance, atrial fibrosis, and degradation of gap junction protein identified as potential mechanistic contributors.

Heart rate variability during carbachol-induced REM sleep and cataplexy

The nucleus pontis oralis (NPO) exerts an executive control over REM sleep. Cholinergic input to the NPO is critical for REM sleep generation. In the cat, a single microinjection of carbachol (a cholinergic agonist) into the NPO produces either REM sleep (REMc) or wakefulness with muscle atonia (cataplexy, CA).In order to study the central control of the heart rate variability (HRV) during sleep, we conducted polysomnographic and electrocardiogram recordings from chronically prepared cats during REMc, CA as well as during sleep and wakefulness. Subsequently, we performed statistical and spectral analyses of the HRV.The heart rate was greater during CA compared to REMc, NREM or REM sleep. Spectral analysis revealed that the low frequency band (LF) power was significantly higher during REM sleep in comparison to REMc and CA. Furthermore, we found that during CA there was a decrease in coupling between the RR intervals plot (tachogram) and respiratory activity. In contrast, compared to natural behavioral states, during REMc and CA there were no significant differences in the HRV based upon the standard deviation of normal RR intervals (SDNN) and the mean squared difference of successive intervals (rMSSD).In conclusion, there were differences in the HRV during naturally-occurring REM sleep compared to REMc. In addition, in spite of the same muscle atonia, the HRV was different during REMc and CA. Therefore, the neuronal network that controls the HRV during REM sleep can be dissociated from the one that generates the muscle atonia during this state.

Heart rate variability, but not heart rate, is associated with handgrip strength and mortality in older Africans at very low cardiovascular risk: A population-based study

A high heart rate and a low heart rate variability at rest are established predictors of various forms of functional impairment, morbidity, and mortality [1–6]. Two explanations can be given for these associations. On one hand, a high heart rate and a low heart rate variability are thought to reflect dysfunction of the flexible autonomic regulation of the heart rate in particular and of the body's functioning in general that arises during ageing [3–5]. On the other hand, a high heart rate and a low heart rate variability are brought about by cardiovascular risk factors, such as obesity, hyperlipidaemia, diabetes, hypertension, and physical inactivity [2,3,7–9]. Since research on heart rate and heart rate variability has almost exclusively been conducted in western populations with an affluent sedentary lifestyle and high prevalences of these risk factors, it has been difficult to determine whether or not heart rate and heart rate variability are associated with functional impairment, morbidity, and mortality independently of cardiovascular risk factors.

Left ventricular diastolic function in diabetes mellitus type 2 patients: correlation with heart rate and its variability.

To assess the prevalence of left ventricular diastolic dysfunction in a population of patients with type 2 diabetes mellitus; to determine correlation of diastolic dysfunction with heart rate and its variability. The study included 202 patients with type 2 diabetes mellitus. Echocardiography was performed with special reference to diastolic function, and heart rate variability was analysed using standard deviation of normal RR intervals, root mean square of successive differences and percentage of successive R-R intervals greater than 50ms (pNN 50%) in a 24-h electrocardiogram recording. Diastolic dysfunction is present in 79% of type 2 diabetes mellitus patients: grade 1 in 52%, grade 2 in 26% and grade 3 in 1% of patients. The subjects with grade 1 diastolic dysfunction had a statistically significantly higher heart rate variability compared with those with grade 2 diastolic dysfunction (LSD, post hoc test, p=0.001). In the group with diastolic dysfunction, grade 2 reduced heart rate variability was recorded in 83% of patients (37 and 7% for grade 1 and normal diastolic function). An increase in the severity of diastolic dysfunction was associated with decreased heart rate variability and increased heart rate. Progression of diastolic dysfunction is associated with a significantly greater prevalence of reduced heart rate variability, which is accompanied by increased heart rate.

Effect of ghrelin on autonomic activity in healthy volunteers

Ghrelin is a novel growth hormone (GH)-releasing peptide originally isolated from the stomach. Recently, we have shown that ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction. In the present study, we evaluated the effect of ghrelin on autonomic nerve activity in healthy human subjects. An intravenous bolus of human synthetic ghrelin (10μg/kg) was administered to 10 healthy men (mean age, 33 years). Holter monitoring assessment was performed before and during 2h after the ghrelin therapy. The standard deviation of normal RR intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent RR intervals (rMSSD), high-frequency power (HF), and low-frequency power (LF) were analyzed. Blood samples were also obtained before and after the therapy. A single administration of ghrelin decreased both heart rate and blood pressure. Interestingly, ghrelin significantly decreased the LF and LF/HF ratio of heart rate variability and increased the SDNN, rMSSD, and HF. Ghrelin also elicited a marked increase in circulating GH, but not insulin-like growth factor-1. These data suggest that ghrelin might suppress cardiac sympathetic nerve activity and stimulate cardiac parasympathetic nerve activity.

Effect of set configuration on hemodynamics and cardiac autonomic modulation after high-intensity squat exercise.

The aim of this study was to compare the effect of two different high-intensity resistance exercise (RE) set configurations on the following: systolic blood pressure (SBP), rate pressure product (RPP), heart rate (HR) variability (HRV), and HR complexity (HRC). Ten well-trained males performed three parallel squat sets until failure (traditional training; TT) with the four repetitions maximum load (4RM), and a rest of 3min between sets. Thereafter, participants performed a cluster training session (CT) of equated load but with resting time distributed between each repetition. Dependent variables were recorded before, during, and after RE. Mean SBP (25·7 versus 10·9% percentage increase; P=0·016) and RPP (112·5 versus 69·9%; P=0·01) were significantly higher in TT. The decrease in HRV after exercise and the drop of HRC during exercise were similar in CT and TT. Change of standard deviation of normal RR intervals after TT correlated with change in SBP (r=0·803; P=0·009) while the change of Sample Entropy during exercise correlated with the increment of RPP during CT (ρ=-0·667; P=0·05). This study suggests that set configuration influences acute cardiovascular responses during RE. When intensity, volume and work-to-rest ratio are equated, CT is less demanding in terms of SBP and RPP. A greater hemodynamic response during exercise would be associated with a faster parasympathetic recovery.

Abstract P105: Sleep Disordered Breathing and Cardiac Autonomic Modulation in Adolescents - Penn State Child Cohort (PSCC) Study

Objectives: To investigate the relationship between sleep disordered breathing (SDB) and cardiac autonomic modulation (CAM) in a population-based sample of adolescents. Methods: We used available data from 400 adolescents who completed the follow up examinations in the population-based PSCC study. 1-night polysomnography was used to assess apnea hypopnea index (AHI). AHI was used to define no-SDB (AHI&lt;1), mild SDB (1≤AHI&lt;5), and moderate SDB (AHI≥5). CAM was assessed by heart rate variability (HRV) analysis of beat-to-beat normal R-R intervals from a 39-hour high resolution Holter ECG. The HRV indices in frequency domain [high frequency power (HF), low frequency power (LF), and LF/HF ratio] and time domain [standard deviation of normal RR intervals (SDNN), and the square root of the mean squared difference of successive normal RR intervals (RMSSD), and heart rate (HR)] were calculated on a 30-minute basis (78 repeated measures). Mixed-effects models were used to assess the SDB and HRV relationship. Results: The mean age was 16.9 yrs (SD=2.19), with 54% male and 77% white. The mean (SD) AHI were 0.52 (0.26), 2.38 (1.03), and 12.27 (14.54) for no-, mild-, and moderate-SDB participants. The age, race, sex, and BMI percentile adjusted mean (SE) HRV indices across three SDB groups are presented in Table 1. In summary, sleep disordered breathing was associated with lower HRV and higher HR in this population-based adolescent sample, with a significant dose-response relationship. Conclusion: moderate SDB in adolescents is already associated with lower HRV, indicative of sympathetic activation and lower parasympathetic modulation, which has been associated with cardiac events in adults.

Statistical, spectral and non-linear analysis of the heart rate variability during wakefulness and sleep

As a first step in a program designed to study the central control of the heart rate variability (HRV) during sleep, we conducted polysomnographic and electrocardiogram recordings on chronically-prepared cats during semi- restricted conditions. We found that the tachogram, i.e. the pattern of heart beat intervals (RR intervals) was deeply modified on passing from alert wakefulness through quiet wakefulness (QW) to sleep. While the tachogram showed a rhythmical pattern coupled with respiratory activity during non-REM sleep (NREM), it turned chaotic during REM sleep. Statistical analyses of the RR intervals showed that the mean duration increased during sleep. HRV measured by the standard deviation of normal RR intervals (SDNN) and by the square root of the mean squared difference of successive intervals (rMSSD) were larger during REM and NREM sleep than during QW. SD-1 (a marker of short- term variability) and SD-2 (a marker of long-term variability) measured by means of Poincaré plots increased during both REM and NREM sleep compared to QW. Furthermore, in the spectral analysis of RR intervals, the band of high frequency (HF) was larger in NREM and REM sleep in comparison to QW, whereas the band of low frequency (LF) was larger only during REM sleep in comparison to QW. The LF/HF ratio was larger during QW compared either with REM or NREM sleep. Finally, sample entropy analysis used as a measure of complexity, was higher during NREM in comparison to REM sleep. In conclusion, HRV parameters, including complexity, are deeply modified across behavioral states.

Utility of a novel risk score for prediction of ventricular tachycardia and cardiac death in chronic Chagas disease - the SEARCH-RIO study

The SEARCH-RIO study prospectively investigated electrocardiogram (ECG)-derived variables in chronic Chagas disease (CCD) as predictors of cardiac death and new onset ventricular tachycardia (VT). Cardiac arrhythmia is a major cause of death in CCD, and electrical markers may play a significant role in risk stratification. One hundred clinically stable outpatients with CCD were enrolled in this study. They initially underwent a 12-lead resting ECG, signal-averaged ECG, and 24-h ambulatory ECG. Abnormal Q-waves, filtered QRS duration, intraventricular electrical transients (IVET), 24-h standard deviation of normal RR intervals (SDNN), and VT were assessed. Echocardiograms assessed left ventricular ejection fraction. Predictors of cardiac death and new onset VT were identified in a Cox proportional hazard model. During a mean follow-up of 95.3 months, 36 patients had adverse events: 22 new onset VT (mean±SD, 18.4±4‰/year) and 20 deaths (26.4±1.8‰/year). In multivariate analysis, only Q-wave (hazard ratio, HR=6.7; P<0.001), VT (HR=5.3; P<0.001), SDNN<100 ms (HR=4.0; P=0.006), and IVET+ (HR=3.0; P=0.04) were independent predictors of the composite endpoint of cardiac death and new onset VT. A prognostic score was developed by weighting points proportional to beta coefficients and summing-up: Q-wave=2; VT=2; SDNN<100 ms=1; IVET+=1. Receiver operating characteristic curve analysis optimized the cutoff value at >1. In 10,000 bootstraps, the C-statistic of this novel score was non-inferior to a previously validated (Rassi) score (0.89±0.03 and 0.80±0.05, respectively; test for non-inferiority: P<0.001). In CCD, surface ECG-derived variables are predictors of cardiac death and new onset VT.

Comparison of particulate matter dose and acute heart rate variability response in cyclists, pedestrians, bus and train passengers

Exposure to airborne particulate matter (PM) has been linked to cardiovascular morbidity and mortality. Heart rate variability (HRV) is a measure of the change in cardiac autonomic function, and consistent links between PM exposure and decreased HRV have been documented in studies. This study quantitatively assesses the acute relative variation of HRV with predicted PM dose in the lungs of commuters. Personal PM exposure, HR and HRV were monitored in 32 young healthy cyclists, pedestrians, bus and train passengers. Inhaled and lung deposited PM doses were determined using a numerical model of the human respiratory tract which accounted for varying ventilation rates between subjects and during commutes. Linear mixed models were used to examine air pollution dose and HRV response relationships in 122 commutes sampled. Elevated PM2.5 and PM10 inhaled and lung deposited doses were significantly (p<0.05) associated with decreased HRV indices. Percent declines in SDNN (standard deviation of normal RR intervals) relative to resting, due to an inter-quartile range increase in PM10 lung deposited dose were stronger in cyclists (−6.4%, 95% CI: −11.7, −1.3) and pedestrians (−5.8%, 95% CI: −11.3, −0.5), in comparison to bus (−3.2%, 95% CI: −6.4, −0.1) and train (−1.8%, −7.5, 3.8) passengers. A similar trend was observed in the case of PM2.5 lung deposited dose and results for rMSSD (the square root of the squared differences of successive normal RR intervals) followed similar trends to SDNN. Inhaled and lung deposited doses accounting for varying ventilation rates between modes, individuals and during commutes have been neglected in other studies relating PM to HRV. The findings here indicate that exercise whilst commuting has an influence on inhaled PM and PM lung deposited dose, and these were significantly associated with acute declines in HRV, especially in pedestrians and cyclists.

Beta blockers or combination of beta blocker with ivabradine better alters the course of heart failure with reduced ejection fraction when the target heart rate is achieved

β-blockers (BB) and ivabradine (I) has been shown to be beneficial in heart failure with reduced EF (HFREF). The main benefit of I derives from heart rate reduction (HRR), whereas BB have broader spectrum of action. We conducted this study to evaluate whether HRR plays a major role in the treatment of HFREF in pts on standard therapy. Methods: 180 pts (55 female) 62±9 years with postinfarction HFREF (EF≤35%) on standard therapy with ACEI/ARB, spironolacton, loop diuretics and in sinus rhythm were randomized to two groups to receive nebivolol (N) titrated up to the achievement of the target HRR (THRR) <70 BPM or I titrated to 10mg BID in order to achieve THRR. THRR were achieved in 43 N tolerated pts, and 56 pts on I and the rest received the combination of N and I on order to reach THRR. All pts on N alone and the same number of pts on I or N+I were selected for the study and comprised 3 groups. EchoCG indexes of LV EDV, ESV and LAV, septal E/Em, mean longitudinal LV strain rate (LSR), Tei index (TI) as IVCT+IVRT/ET, as well as the total ischemic burden (TIB) as a total time of ST segment depressions ≥ 1 mm and ≥1 min duration and HRV as a standard deviation of normal RR intervals (SDNN) were measured by 24-hour ECG monitoring at baseline, 90 and 180 days follow up. Results: After 90 days follow up all parameters were similar between groups but significantly improved at the same degree within each group compared with baseline (p < 0.05). After 180 days follow up LV remodeling was better altered, contractility, SDNN parameters significantly improved at the same degree in N and N+I groups compared with I without differences between N and N+I, TIB did not differ between groups (ESVI: N 59.7±7.4 ml/m2 vs N+I 60.5±7.6 ml/m2 vs I 69.8±7.9* ml/m2, *p<0.05; EDVI: N 95.8±9.4 ml/m2 vs N+I 93.4±9.2 ml/m2 vs I 109.4±9.8* ml/m2, *p<0.05; TI: N 0.76±0.24 vs N+I 0.73±0.22 vs I 0.89±0.28*, *p < 0.05; E/Em: N 11.4±4.1 vs N+I 11.1±4.5 vs I 14.8±5.2*, *p < 0.05; TIB: N 35±13 min vs N+I 34±10 min vs I 33±9 min, p=NS; SDNN: N 103.04±15 ms vs N+I 104.06±16 ms vs I 126±18*ms, *p<0.05; LSR: N 1.59±0.16 vs N+I 1.54±0.14, 1.30±0.12*, *p < 0.05). Both N and I were well tolerated by pts throughout follow up. Conclusion: BB or in case of intolerance their combination with I to further reduce HR are more beneficial than reduction of HR at the same degree solely with I. Additional properties of BB are of importance and neurohormonal modulation with HR reduction better alters the course of HF.

Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist on Cardiac Autonomic Functions of Rats During Acute and Chronic Inhibition of Nitric Oxide Synthesis

We studied the effect of losartan on baroreflex sensitivity (BRS) and heart rate variability (HRV) of adult Wistar rats during acute and chronic inhibition of nitric oxide synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME). Chronic L-NAME administration (50 mg/kg per day for 7 days, orally through gavage) increased mean arterial pressure (MAP), heart rate but significantly decreased BRS. In addition, a significant fall of standard deviation of normal RR intervals, total spectral power, high frequency spectral power and a rise of low frequency to high frequency (LF: HF) ratio was seen. Acute L-NAME administration (30 mg/kg, i.v. bolus dose) also raised MAP and impaired HRV but it was associated with augmented BRS for bradycardia reflex. Losartan treatment (10 mg/kg, i.v.) in both acute and chronic L-NAME treated rats, decreased MAP but the difference was not significant. On the other hand, losartan administration normalized depressed BRS for bradycardia reflex and significantly reduced LF to HF ratio in chronic L-NAME treated rats. But this improvement was not observed in acute L-NAME group. These results indicate importance of mechanisms other than renin-angiotensin system in the pressor response of both acute as well as chronic L-NAME. However, autonomic dysregulation especially following chronic L-NAME appears to be partly angiotensin dependent.

Abstract P203: Association of Sleep Characteristics with Heart Rate Variability: Chicago Area Sleep Study

Introduction: Autonomic nervous system (ANS) dysfunction may contribute to the elevated incidence of hypertension, diabetes and coronary heart disease (CHD) among persons with shortened sleep duration. However, prior studies were conducted in adults who had obstructive sleep apnea (OSA), a correlate of short sleep, or using experimental designs that restricted sleep. To explore whether sleep duration is associated with ANS function in adults free from OSA, we tested whether sleep duration was associated with heart rate variability (HRV) indices that represent autonomic modulation of heart rate. Methods: The Chicago Area Sleep Study (CASS) identified men and women ages 35-64 via commercially available telephone listings. Data from 406 participants who had an apnea/hypopnea index&lt;15 based on 1 night of in-home apnea detection (ApneaLink TM ) were studied. Participants wore wrist actigraphs for 7 days (Actiwatch TM ) to determine average sleep duration, sleep percentage (% of time during overnight sleep interval spent sleeping) and minutes of wake after sleep onset (WASO). A validated questionnaire, the Epworth Sleepiness Scale (ESS), was used to determine daytime sleepiness. Electrocardiograms were continuously recorded from participants for 10 minutes s from supine participants; time and frequency domain HRV indices were calculated from the RR interval to estimate overall autonomic modulation of heart rate (standard deviation of normal RR intervals [SDNN]) and parasympathetic modulation heart rate (high frequency power [HF], square root of the mean squared difference of successive R-R intervals [rMSSD]). Height and weight were measured and hypertension and diabetes were determined according to JNC-VII and American Diabetes Association 2010 criteria, respectively. Results: Participants’ mean age was 47.5 years, and 56% were female. Average sleep duration was 7.03 hours (SD=1.15), sleep percentage was 83% (SD=20.1), WASO was 41.4 min (SD=21) and the ESS score was 6.75 (SD=4.1). Following adjustment for age, race, sex, BMI, hypertension, diabetes, physical activity and smoking, sleep duration (per 1 hr) was significantly (p&lt;0.01) inversely associated with SDNN (β=−2.5, SE=1.12), rMSSD (β=−2.6, SE=1.1) and log-transformed HF (β=−0.11, SE=0.05). Findings were similar in the subset of 285 participants with AHI&lt;5. Conclusions: In contrast to prior studies, shorter sleep duration was associated with more favorable parasympathetic modulation of HR. These unexpected findings may suggest that ANS dysfunction associated with OSA may be attributed to hypoxemia rather than the direct effects of shortened sleep duration.