SD Of RR Intervals Research Articles

Heart rate variability and lifetime risk of cardiovascular disease: the Atherosclerosis Risk in Communities Study

PurposeThe purpose of this study was to estimate the heart rate variability (HRV)–related lifetime cardiovascular disease (CVD) risk. MethodsWe followed 9744 participants without baseline CVD and used a life-table approach to estimate lifetime CVD risk (coronary heart disease, heart failure, and stroke) from 45 through 85 years according to several HRV measures (the SD of RR intervals [SDNN], the root mean square of successive differences of successive RR intervals, the mean of all normal RR intervals [meanNN], low-frequency [LF] and high-frequency [HF] power, and the LF/HF ratio). ResultsDuring 192,110 person-years of follow-up, we documented 2856 CVD events. Cox regression analyses with the false discovery rate method correction showed independent associations of SDNN, meanNN, LF, and LF/HF in women with CVD. Lifetime CVD risks in the lowest compared with the highest tertile were significantly increased in men for LF/HF (51.3% [95% confidence interval, 47.3–54.7] vs. 43.9% [40.1–47.2]), and in women for SDNN (39.4% [36.0–43.0] vs. 29.9% [26.3–33.0]), meanNN (39.3% [35.7–42.7] vs. 28.9% [25.7–31.7]), LF (39.4% [35.9–43.0] vs. 30.0% [26.2–33.2]), and LF/HF (37.6% [33.9–40.9] vs. 30.0% [26.8–32.7]). ConclusionsGreater HRV was modestly associated with lower lifetime CVD risk.

Heart Rate Variability and Incident Stroke

Low heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been associated with increased all-cause and cardiovascular mortality. We examined the association between reduced HRV and incident stroke in a community-based cohort. The Atherosclerosis Risk in Communities (ARIC) study measured HRV using 2-minute ECG readings in 12 550 middle-aged adults at baseline (1987-1989). HRV indices were calculated using the SD of RR intervals (SDNN), the mean of all normal RR intervals (meanNN), the root mean square of successive differences of successive RR intervals (RMSSD), low (LF) and high (HF) frequency power, and the LF/HF ratio. All HRV measures were categorized into quintiles. Incident stroke was adjudicated through 2011. Cox regression was used to estimate hazard ratios (HRs) with the lowest HRV quintile as the reference, with and without stratification by prevalent diabetes mellitus. Over a median follow-up of 22 years, 816 (6.5%) participants experienced incident stroke. After covariate adjustment, there was no strong evidence of association between HRV and stroke risk. In stratified analyses, the lowest HRV quintile was associated with higher stroke risk compared with the highest quintile for SDNN (HR, 2.0, 95% confidence interval, 1.1-4.0), RMSSD (HR, 1.7; 95% confidence interval, 0.9-3.2), LF (HR, 1.5; 95% confidence interval, 0.8-3.0), and HF (HR, 1.7; 95% confidence interval, 0.9-3.0) only among people with diabetes mellitus. Lower HRV was associated with higher risk of incident stroke among middle-aged adults with prevalent diabetes mellitus but not among people without diabetes mellitus.

Relation of impaired interorgan communication and parasympathetic activity in chronic heart failure and multiple-organ dysfunction syndrome

BackgroundWe investigated the relationship of impaired autonomic function and severity of illness in chronic heart failure (CHF) and multiple-organ dysfunction syndrome (MODS) as an end stage of CHF. Furthermore, we assessed the link of parasympathetic modulation of the heart rate and inflammatory activation in CHF and MODS. MethodsSixty-five patients admitted for worsening of CHF were retrospectively enrolled in this study. In addition, 65 age- and sex-matched patients with pronounced MODS were assigned for comparison of autonomic function and C-reactive protein in patients with CHF or MODS, respectively. Heart rate variability (HRV) parameters of the time and frequency domain as markers of autonomic function were analyzed from 24-hour Holter electrocardiograms. ResultsThe more pronounced the severity of illness as expressed by the Acute Physiology and Chronic Health Evaluation score, the more the HRV was impaired. This effect was particularly seen for overall variability (SD of RR intervals) and HRV parameters characterizing the parasympathetic modulations of the heart rate (high, very low frequency power). C-reactive protein levels as markers of inflammation were inversely related to high and very low frequencies. ConclusionOur results allow for speculation that autonomic dysfunction in CHF indicates a beginning of uncoupled interorgan communication potentially leading to MODS as characterized by disruption of communication between the organs.

Autonomic modulation of repolarization instability in patients with heart failure prone to ventricular tachycardia

QT variability (QTV) signifies repolarization lability, and increased QTV is a risk predictor for sudden cardiac death. The aim of the present study was to investigate the role of autonomic nervous system activity on QTV. This study was performed in 29 subjects: 10 heart failure (HF) patients with spontaneous ventricular tachycardia [HFVT(+)], 10 HF patients without spontaneous VT [HFVT(-)], and 9 subjects with structurally normal hearts (HNorm). The beat-to-beat QT interval was measured on 3-min records of surface ECGs at baseline and during interventions (atrial pacing and esmolol, isoprenaline, and atropine infusion). Variability in QT intervals was expressed as the SD of all QT intervals (SDQT). The ratio of the SDQT to SD of RR intervals (SDRR) was calculated as an index of QTV normalized to heart rate variability. There was a trend toward a higher baseline SDQT-to-SDRR ratio in the HFVT(+) group compared with the HFVT(-) and HNorm groups (P = 0.09). SDQT increased significantly in the HFVT(+) and HFVT(-) groups compared with the HNorm group during fixed-rate atrial pacing (P = 0.008). Compared with baseline, isoprenaline infusion increased SDQT in HNorm subjects (P = 0.02) but not in HF patients. SDQT remained elevated in the HFVT(+) group relative to the HNorm group despite acute β-adrenoceptor blockade with esmolol (P = 0.02). In conclusion, patients with HF and spontaneous VT have larger fluctuations in beat-to-beat QT intervals. This appears to be a genuine effect that is not solely a consequence of heart rate variation. The effect of acute autonomic nervous system modulation on QTV appears to be limited in HF patients.

Relation of heart rate variability to serum levels of C-reactive protein, interleukin 6, and 10 in patients with sepsis and septic shock

Purpose The aim of the study was to investigate possible associations between different heart rate variability (HRV) indices and various biomarkers of inflammation in 45 septic patients. Materials and Methods We daily assessed HRV in the time domain (SD of RR intervals [SDNN]), frequency domain (low [LF], high frequency [HF], LF/HF as an indicator of sympathovagal balance); the 2 values of SD (SD1, SD2) from the Poincaré plot; and measured C-reactive protein, interleukin 6, and interleukin 10 serum levels in patients with sepsis and mean Sequential Organ Failure Assessment score (SOFA) 10 or lower (n = 25) and septic shock (SOFA > 10, n = 20) for 6 days. Results C-reactive protein exhibited significant negative correlations with LF ( r = −0.78), LF/HF ( r = −0.61), and SDNN ( r = −0.79) and positive correlations with HF ( r = 0.80) and SD1/SD2 ( r = 0.66), whereas interleukin 10 was positively correlated with HF ( r = 0.71) and negatively with LF ( r = −0.89) and LF/HF ( r = −0.66) in septic shock patients ( P < .05 for all comparisons). Standard deviation of RR intervals and HF proved to be independent predictors of the severity of disease ( β slope [B] = −1.091; P = .013; 95% confidence interval [CI], −1.43 to −0.74, and B = 0.78; P = .022; 95% CI, 0.21-1.35, respectively). Conclusions Our data suggest that low HRV and sympathovagal balance during septic shock are associated with both an increased hyperinflammatory and antiinflammatory response.

Time Course and Predictors of Autonomic Dysfunction After Ablation of the Slow Atrioventricular Nodal Pathway

Withdrawal of parasympathetic tone has been reported after ablation in the posteroseptal right atrium and has been attributed to injury of vagal efferent fibers. The purpose of this study was to assess the time course and predictors of autonomic dysfunction after slow pathway ablation. In 30 patients with AV nodal reentrant tachycardia, time- and frequency-domain measures of heart rate variability (HRV) were measured before, 30 minutes after, and 1 day after slow pathway ablation. There were significant reductions in mean RR interval (724 +/- 163 vs 836 +/- 164 ms, P < 0.05), SD of RR intervals (29 +/- 17 vs 40 +/- 18 ms, P < 0.05), root mean squared difference (15 +/- 8 vs 29 +/- 17 ms, P < 0.05), and high frequency power (4.1 +/- 0.4 vs 4.5 +/- 0.6 log10ms2, P < 0.05) 30 minutes after ablation. However, these parameters returned to baseline 1 day after ablation. Multivariate regression identified isoproterenol dose during the diagnostic study (P = 0.02) and radiofrequency duration (P = 0.02) as statistically significant predictors of heart rate change (R2= 0.45). These findings suggest that changes in autonomic tone after ablation in the posteroseptal right atrium are transitory and resolve within 1 day of the procedure. These short-term changes may be related to procedural variables rather than direct injury to vagal efferent fibers.

Measures of heart period variability as predictors of mortality in hospitalized patients with decompensated congestive heart failure

Depressed heart rate variability (HRV) is a powerful independent predictor of a poor outcome in patients with chronic and stable congestive heart failure (CHF). However, the prognostic value of HRV analysis in patients hospitalized for decompensated CHF is not known. The aim of this study was to investigate whether HRV parameters obtained during admission for decompensated CHF could predict survival after hospital discharge. We studied 199 patients (131 men, aged 60 ± 14 years) with a previous diagnosis of New York Heart Association class III or IV CHF who were admitted to the hospital for decompensated CHF. Twenty-four–hour Holter recordings were obtained on admission, and measures of HRV were calculated in the time and frequency domain. During a mean follow-up of 312 ± 150 days, 40 patients (21.1%) died. Kaplan-Meier analysis indicated that patients with SD of the RR intervals over a 24-hour period (p = 0.027), SD of all 5-minute mean RR intervals (p = 0.043), total power (p = 0.022), and ultra–low-frequency power (p = 0.008) in the lower tertile were at a higher risk of death. In a multivariate Cox regression model, the same indexes in the lower tertile were independent predictors of mortality: SD of the RR intervals over a 24-hour period (risk ratio [RR] 2.2, 95% confidence interval [CI] 1.05 to 4.3, p = 0.036), SD of all 5-minute mean RR intervals (RR 2.1, 95% CI 1.05 to 4.2, p = 0.04), total power (RR 2.2, 95% CI 1.08 to 4.2, p = 0.03), and ultra–low-frequency power (RR 2.6, 95% CI 1.3 to 5.3, p = 0.007). Therefore, the severity of autonomic perturbations during hospital admission for CHF decompensation, as reflected by measures of overall HRV, can predict survival after hospital discharge. Together with previous studies, our findings suggest that indexes of overall HRV provide useful prognostic information in the full spectrum of CHF severity.

Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A1 adenosine receptor.

To investigate whether altered function of adenosine receptors could contribute to sinus node or atrioventricular (AV) nodal dysfunction in conscious mammals, we studied transgenic (TG) mice with cardiac-specific overexpression of the A1 adenosine receptor (A1AR). A Holter ECG was recorded in seven freely moving littermate pairs of mice during normal activity, exercise (5 min of swimming), and 1 h after exercise. TG mice had lower maximal heart rates (HR) than wild-type (WT) mice (normal activity: 437 +/- 18 vs. 522 +/- 24 beats/min, P < 0.05; exercise: 650 +/- 13 vs. 765 +/- 28 beats/min, P < 0.05; 1 h after exercise: 588 +/- 18 vs. 720 +/- 12 beats/min, P < 0.05; all values are means +/- SE). Mean HR was lower during exercise (589 +/- 16 vs. 698 +/- 34 beats/min, P < 0.05) and after exercise (495 +/- 16 vs. 592 +/- 27 beats/min, P < 0.05). Minimal HR was not different between genotypes. HR variability (SD of RR intervals) was reduced by 30% (P < 0.05) in TG compared with WT mice. Pertussis toxin (n = 4 pairs, 150 microg/kg ip) reversed bradycardia after 48 h. TG mice showed first-degree AV nodal block (PQ interval: 42 +/- 2 vs. 37 +/- 2 ms, P < 0.05), which was diminished but not abolished by pertussis toxin. Isolated Langendorff-perfused TG hearts developed spontaneous atrial arrhythmias (3 of 6 TG mice vs. 0 of 9 WT mice, P < 0.05). In conclusion, A1AR regulate sinus nodal and AV nodal function in the mammalian heart in vivo. Enhanced expression of A1AR causes sinus nodal and AV nodal dysfunction and supraventricular arrhythmias.

Changes of autonomic cardiac profile after a 3-week integrated body weight reduction program in severely obese patients.

The autonomic control of the heart is abnormal in obese subjects due to a prevalence of sympathetic over parasympathetic limb of the autonomic balance. We evaluated the effects of a short-term (3 weeks) integrated body weight reduction program (consisting of energy restricted diet and high-intensity exercise training) on heart rate variability (HRV) in severely obese, normotensive patients. The HRV was evaluated both in the time and frequency domain over a 18-hour Holter recording period obtained before and at the end of the third week. Three-week body weight reduction program reduced BMI (from 41.4 +/- 4.6 to 39.5 +/- 4.3 kg/m2, -4.6%, p<0.0001) and heart rate (from 77.8 +/- 8.6 to 73.6 +/- 8.7 b/min, p=0.0003). Significant changes in the autonomic profile were observed both in the time and frequency domain (SD of RR interval, SDRR: +16.1%; mean squared successive difference: (MSSD) +16.7%; percentage of RR intervals differing more than 50 msec from the preceding one, pNN50: +31.8%; low frequency oscillation, LF: +17.1%; high frequency oscillation, HF: +/- 18.2%). In conclusion, this study demonstrates that a short-term, integrated body weight reduction program is able to favorably modify the autonomic profile in a population of normotensive, severely obese subjects. The reduction of heart rate and the increase in parasympathetic activity may consistently contribute to a reduction of the risk of cardiovascular morbidity and of sudden cardiac death, still high in this patients' group.

Effects of bisoprolol on heart rate variability in heart failure

Analysis of heart rate variability (HRV) provides a noninvasive index of autonomic nervous system activity. HRV has been shown to be reduced in heart failure. Preliminary data indicate that β blockers improve clinical status in patients with heart failure, but HRV improvement remains to be demonstrated. Fifty-four patients from the randomized double-blind, placebo-controlled Cardiac Insufficiency Bisoprolol Study were included in the HRV study. The bisoprolol daily dose was 5 mg once daily. We assessed HRV during 24-hour Hotter recordings before randomization and after 2 months of treatment. HRV was measured in the time domain by rootmean-square successive differences (rMSSD), the percentage of adjacent RR differences >50 ms (pNN50), and the SD of RR intervals (SDNN), and in the frequency domain by high-frequency (0.16 to 0.40 Hz) and low-frequency (0.04 to 0.15 Hz) power. Most patients were in New York Heart Association functional class III. The mean left ventricular ejection fraction was 27 ± 7%, and heart failure was idiopathic or ischemic. After 2 months, the patients receiving bisoprolol had a reduced mean heart rate compared with that in placebo patients (p = 0.0004). Bisoprolol increased 24-hour rMSSD (p = 0.04) and 24-hour pNN50 (p = 0.04), daytime SDNN (p = 0.05), and daytime high-frequency power (p = 0.03) power. Bisoprolol induced a significant increase in HRV parameters related to parasympathetic activity in heart failure. Increased vagal tone may contribute to the protective effect of β blockers and may have prognostic implications.

Comparison of different methods for assessing sympathovagal balance in chronic congestive heart failure secondary to coronary artery disease

Twenty-five patients (aged 62 ± 2 years) with stable, moderate to severe ischemic congestive heart failure (CHF) (New York Heart Association class II/III: 15/10; ejection fraction 21.6 ± 2%; and peak oxygen uptake 13.6 ± 0.7 ml/kg/min) were studied to evaluate the ability of different methods to characterize autonomic tone in chronic CHF. Sympathovagal balance was assessed by: (1) heart rate variability in the time domain, assessed by the SD of RR intervals; (2) heart rate variability in the frequency domain, assessed by low- (0.03 to 0.14 Hz) and high- (0.18 to 0.40 Hz) frequency components of heart rate variability by autoregressive power spectral analysis; (3) 24-hour, daytime and nighttime heart rate; (4) submaximal heart rate during upright bicycle exercise, with respiratory gas analysis to obtain peak oxygen uptake; and (5) radiolabeled norepinephrine spillover. These methods did not correlate, with the exception of day and nighttime heart rate (r = 0.74; p < 0.001) and the expected inverse correlation between low and high frequency (r = −0.92; p < 0.001). No method correlated significantly with peak oxygen uptake, exercise tolerance or ejection fraction. After 8 weeks of physical training at home, all methods showed improvement in autonomic balance: increases in SD of RR intervals (+21%; p < 0.02) and high frequency (+41%; p < 0.007), and decreases in low frequency (−19%; p < 0.002), low-/high-frequency ratio (−48%; p < 0.03), norepinephrine spillover (−28.9%; p < 0.03), 24-hour heart rate (−2.7%; p < 0.005) and submaximal heart rate (−10.8%; p < 0.01). However, neither the absolute values nor percent changes of the individual measures of autonomic function after training showed a significant correlation between each other. In patients with CHF, the individual parameters of autonomic control reflect different aspects of circulatory control. A comprehensive description of autonomic tone probably needs multiple methods.