Heart rate variability and its changes over 5 years in older adults.

PURPOSE: to characterise the association between age, ageing and heart rate variability (HRV) in older individuals, 585 adults age >65 years with two 24-h Holter recordings in the Cardiovascular Health Study were studied. METHODS: heart rate (HR), ventricular premature contractions (VPCs), atrial premature contractions (APCs), frequency-domain, ratio-based and non-linear HRV and heart rate turbulence (HRT) were examined cross-sectionally by 5-year age groups and prospectively over 5 years. Analyses adjusted for gender, lower versus elevated cardiovascular (CV) risk and for the change in CV risk. RESULTS: HR declined, and VPCs and APCs increased per 5-year increase in age. Frequency-domain HRV decreased more at 65-69, less at 70-74 and minimally at > or =75 years, independent of CVD risk or change in CVD risk. Ratio and non-linear HRV continued to decline to > or =75 years old. Ratio HRV and HRT slope were more strongly related to CVD risk than frequency-domain HRV. CONCLUSIONS: cardiac autonomic function, assessed by frequency-domain HRV, declines most at 65-70 and levels off at age >75. The decline is independent of CVD risk or change in CVD risk. Ratio-based and non-linear HRV and HRT slope continued to change with increasing age and were more closely related to CVD risk than frequency-domain HRV.

Ambulatory ECG-based T-wave alternans predicts sudden cardiac death in high-risk post-MI patients with left ventricular dysfunction in the EPHESUS study.

BACKGROUND: Exercise microvolt T-wave alternans (TWA) identifies sudden cardiac death (SCD) risk. TWA can be measured from ambulatory ECGs (AECGs) using modified moving average (MMA) method. Whether MMA TWA from AECGs predicts SCD in post-MI patients with left ventricular dysfunction (LVD) is unknown. METHODS: EPHESUS enrolled hospitalized post-MI patients with heart failure and/or diabetes with LVD. Before randomization to drug treatment, AECGs were obtained in 493 patients. Of them, 46 died of cardiovascular causes, including 18 of SCD. Patients alive at end of follow-up (N = 92) were matched with 46 nonsurvivors based on age, gender, and diabetes. MMA TWA was analyzed using MARSPC system (GE Healthcare, Milwaukee, WI, USA). The three highest TWA values from artifact-free periods were averaged for AECG channels corresponding to leads V(1) and V(3). SCD prediction was tested with a prespecified 47 microV cutpoint and at a cutpoint maximizing the separation between SCD patients versus survivors or non-SCD. RESULTS: TWA in either lead was higher for patients with SCD (P < or = 0.05) versus survivors or non-SCD. TWA > or = 47 microV was associated with RR = 5.2 (95%CI = 1.8-13.6, P = 0.002) in V(1) and RR = 5.5 (95% CI = 2.2-13.8, P < 0.001) in V(3) for SCD. The optimal cutpoint for TWA in V(1) was > or = 43 microV (RR = 5.9 [95%CI = 2.2-15.8, P < 0.001]). The optimal cutpoint in V(3) was > or = 47 microV. TWA greater than the optimal cutpoint in either lead was associated with RR = 7.1 (95%CI = 2.7-18.3, P < 0.001) for SCD, with 11 out of 18 patients dying of SCD. CONCLUSIONS: AECG-based TWA measured with MMA is a powerful predictor of SCD in high-risk post-MI patients with LV dysfunction.

Novel measures of heart rate variability predict cardiovascular mortality in older adults independent of traditional cardiovascular risk factors: the Cardiovascular Health Study (CHS).

UNLABELLED: Novel HRV Predicts CV Mortality in the Elderly. BACKGROUND: It is unknown whether abnormal heart rate turbulence (HRT) and abnormal fractal properties of heart rate variability identify older adults at increased risk of cardiovascular death (CVdth). METHODS: Data from 1,172 community-dwelling adults, ages 72 +/- 5 (65-93) years, who participated in the Cardiovascular Health Study (CHS), a study of risk factors for CV disease in people >or=65 years. HRT and the short-term fractal scaling exponent (DFA1) derived from 24-hour Holter recordings. HRT categorized as: normal (turbulence slope [TS] and turbulence onset [TO] normal) or abnormal (TS and/or TO abnormal). DFA1 categorized as low (1). Cox regression analyses stratified by Framingham Risk Score (FRS) strata (low = <10, mid = 10-20, and high >20) and adjusted for prevalent clinical cardiovascular disease (CVD), diabetes, and quartiles of ventricular premature beat counts (VPCs). RESULTS: CVdths (N = 172) occurred over a median follow-up of 12.3 years. Within each FRS stratum, low DFA1 + abnormal HRT predicted risk of CVdth (RR = 7.7 for low FRS; 3.6, mid FRS; 2.8, high FRS). Among high FRS stratum participants, low DFA1 alone also predicted CVdth (RR = 2.0). VPCs in the highest quartile predicted CVdth, but only in the high FRS group. Clinical CV disease predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9, high). Diabetes predicted CVdth in the highest FRS group only (RR = 2.2). CONCLUSIONS: The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth among older adults even after adjustment for conventional CVD risk measures and the presence of CVD.

Nighttime heart rate and survival in depressed patients post acute myocardial infarction.

OBJECTIVES: To determine if: 1) depressed patients with a recent acute myocardial infarction (AMI) have higher nighttime heart rate (HR) than nondepressed patients, and 2) elevated nighttime HR is associated with decreased survival post AMI. Depression is a risk factor for mortality post AMI. It is also associated with sleep disturbances and with elevated HR, which may be more pronounced at night. Resting and 24-hour HR have been found to predict mortality in patient and community samples. METHODS: Ambulatory electrocardiographic data were obtained from 333 depressed patients and 383 nondepressed patients with recent AMI. They were followed for up to 30 months (median = 24 months). RESULTS: Depressed patients had higher nighttime HR (70.7 +/- 0.7 versus 67.7 +/- 0.6 beats per minute (bpm); p = .001), and daytime HR (76.4 +/- 0.7 versus 74.2 +/- 0.6 bpm; p = .02) than nondepressed patients, even after adjusting for potential confounds. Depression (hazard ratio (Haz R) = 2.19; p = .02) and nighttime HR (Haz R = 1.03; p = .004), but not daytime HR, predicted survival after adjusting for other major predictors and for each other. The interaction between nighttime HR and depression on survival approached, but did not achieve, significance (p = .08). CONCLUSIONS: Mean day and nighttime HR values are higher in depressed patients than in nondepressed patients post AMI. Depression and elevated nighttime HR, but not daytime HR, are independent predictors of survival in these patients. Although depressed patients have a higher nighttime HR than nondepressed patients, nighttime HR predicts mortality in both depressed and nondepressed patients.

Autonomic information flow improves prognostic value of heart rate patterns after abdominal aortic surgery.

PURPOSE: Complex autonomic communication can be assessed by autonomic information flow (AIF) functions. The objective was to evaluate new complexity measures involving physiologically relevant time scales to predict the length of stay (LOS) in the hospital after abdominal aortic surgery (AAS). Our hypothesis was that AAS disrupts AIF, that restoration of AIF is necessary for recovery from major surgery, and that measures of AIF are superior to conventional heart rate variability (HRV) measures and equivalent to APACHE IV score in predicting LOS. MATERIALS AND METHODS: Twenty-four-hour Holter recordings were analyzed in 94 patients after AAS for standard time, frequency domain, and several complexity measures of different time scales derived from AIF functions. The risk of staying in the hospital for longer than 7 days as a function of HRV measures and APACHE IV score was modeled by logistic regression. The area under the curve (AUC) of receiver operating characteristic with 95% confidence interval as measure of predictive accuracy was calculated and internally cross-validated. RESULTS: The long-term decay of AIF over 100s (LD100) with cross-validated AUC = 0.67 (0.56-0.79) nearly reached the predictive accuracy of the APACHE IV score with AUC = 0.69 (0.58-0.79). None of the traditional time and frequency domain HRV measures remained in the multivariate models. The LD100 adjusted for ventilatory support with AUC = 0.70 (0.59-0.81) was equivalent to the APACHE IV score in this patient group. Although the strongest correlation between AIF measures and the APACHE IV score was found for LD100, r was only -0.37. CONCLUSIONS: Results confirm the hypothesis that AIF measures characterize pathophysiologic autonomic communication better than traditional HRV measures and may have similar predictive value to the APACHE IV score for LOS. The relative independence of the APACHE IV score and AIF measures suggests that AIF measures could add to clinical risk prediction.

Development of more erratic heart rate patterns is associated with mortality post-myocardial infarction.

Cardiac patients often have sinus arrhythmia of nonrespiratory origin (erratic sinus rhythm [ESR]). ESR was quantified using hourly Poincaré and power spectral heart rate variability plots from normal-to-normal interbeat intervals and hourly values of the short-term fractal scaling exponent and correlations of normal-to-normal intervals in n = 60 nonsurvivors and n = 66 randomly selected survivors in the Cardiac Arrhythmia Suppression Trial. Hours were coded (ABN) as normal (0), borderline (0.5), or ESR (1). t Tests compared ABN for n = 2413 paired hours at baseline and on therapy. ABN was higher in nonsurvivors (0.38 +/- 0.44 vs 0.28 +/- 0.40, baseline, and 0.51 +/- 0.45 vs 0.34 +/- 0.43, on therapy, P < .001). Increased ABN with treatment were greater in nonsurvivors. Normal hours at baseline (relative risk = 0.77; 095% confidence interval, 0.62-0.96, P = .018) and on treatment (relative risk = 0.47; 95% confidence interval, 0.39-0.58) were significantly associated with decreased mortality compared with ESR. Quantification of ESR may identify more vulnerable patients or help monitor the effects of pharmacologic treatment.

Increased ventricular premature contraction frequency during rem sleep in patients with coronary artery disease and obstructive sleep apnea.

BACKGROUND: Patients with obstructive sleep apnea are reported to have a peak of sudden cardiac death at night, in contrast to patients without apnea whose peak is in the morning. We hypothesized that ventricular premature contraction (VPC) frequency would correlate with measures of apnea and sympathetic activity. METHODS: Electrocardiograms from a sleep study of 125 patients with coronary artery disease were evaluated. Patients were categorized by apnea-hypopnea index (AHI) into Moderate (AHI <15) or Severe (AHI>15) apnea groups. Sleep stages studied were Wake, S1, S2, S34, and rapid eye movement (REM). Parameters of a potent autonomically-based risk predictor for sudden cardiac death called heart rate turbulence were calculated. RESULTS: There were 74 Moderate and 51 Severe obstructive sleep apnea patients. VPC frequency was affected significantly by sleep stage (Wake, S2 and REM, F=5.8, p<.005) and by AHI (F=8.7, p<.005). In Severe apnea patients, VPC frequency was higher in REM than in Wake (p=.011). In contrast, patients with Moderate apnea had fewer VPCs and exhibited no sleep stage dependence (p=.19). Oxygen desaturation duration per apnea episode correlated positively with AHI (r(2)=.71, p<.0001), and was longer in REM than in non-REM (p<.0001). The heart rate turbulence parameter TS correlated negatively with oxygen desaturation duration in REM (r(2)=.06, p=.014). CONCLUSIONS: Higher VPC frequency coupled with higher sympathetic activity caused by longer apnea episodes in REM sleep may be one reason for increased nocturnal death in apneic patients.

Heart rate turbulence, depression, and survival after acute myocardial infarction.

OBJECTIVE: Depression is a risk factor for mortality after acute myocardial infarction (AMI), possibly as a result of altered autonomic nervous system (ANS) modulation of heart rate (HR) and rhythm. The purposes of this study were to determine: a) whether depressed patients are more likely to have an abnormal HR response (i.e., abnormal turbulence) to premature ventricular contractions (VPCs), and b) whether abnormal HR turbulence accounts for the effect of depression on increased mortality after AMI. METHODS: Ambulatory electrocardiographic data were obtained from 666 (316 depressed, 350 nondepressed) patients with a recent AMI; 498 had VPCs with measurable HR turbulence. Of these, 260 had normal, 152 had equivocal, and 86 had abnormal HR turbulence. Patients were followed for up to 30 (median = 24) months. RESULTS: Depressed patients were more likely to have abnormal HR turbulence (risk factor adjusted odds ratio = 1.8; 95% confidence interval [CI] = 1.0-3.0; p = .03) and have worse survival (odds ratio = 2.4; 95% CI = 1.2-4.6; p = .02) than nondepressed patients. When HR turbulence was added to the model, the adjusted hazard ratio for depression decreased to 1.9 (95% CI = 0.9-3.8; p = .08), and to 1.6 (95% CI = 0.8-3.4; p = .18) when a measure of HR variability (LnVLF) was added. The hazard was found to differ over time with depression posing little risk for mortality in year 1 but greater risk in years 2 and 3 of the follow up. CONCLUSION: ANS dysregulation may partially mediate the increased risk for mortality in depressed patients with frequent VPCs after an AMI.

Diastolic dysfunction and autonomic abnormalities in patients with systolic heart failure.

BACKGROUND: Patients with systolic heart failure (SHF) often have concomitant diastolic dysfunction (DD). SHF is associated with decreased heart rate variability (HRV), but the impact of degree of DD on HRV in SHF is unclear. METHODS AND RESULTS: HRV was measured in 139 patients, aged 64+/-12 years, 74% male, LVEF 30+/-8%. Patients had stable NYHA class II-III CHF on ACE inhibitors or ATII receptor blockers, with LVEFor=200 pg/ml. Subjects underwent 2-D echocardiography with Doppler assessment and 24-h Holters. Patients were categorized as having impaired relaxation (E-deceleration time>2 SD above age-adjusted normal values (AANV), E/Aor=1; N=30), pseudonormal (E-deceleration time within 2 SD of AANV, E/A=1-2, systolic/diastolic pulmonary vein flow<1; N=25) or restrictive filling patterns (E-deceleration time>2 SD below AANV or/and E/A ratio>or=2; N=84) Differences were adjusted for clinical covariates using UNIANOVA, p<0.05. HRV was reduced and BNP higher in pseudonormal patients compared to impaired relaxation, but this difference was only significant for restrictive vs. impaired filling. Differences remained significant after adjustment for covariates. CONCLUSION: Significantly more abnormal HRV, reflecting greater cardiac autonomic dysfunction, is associated with restrictive DD compared to impaired relaxation.

Low heart rate variability and the effect of depression on post-myocardial infarction mortality.

BACKGROUND: Depression is associated with an increased risk for mortality after acute myocardial infarction (MI). The purpose of this study was to determine whether low heart rate variability (HRV) mediates the effect of depression on mortality. METHODS: Twenty-four-hour ambulatory electrocardiograms were obtained from 311 depressed patients with a recent acute MI who were enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial and from 367 nondepressed patients who met the ENRICHD medical inclusion criteria. Standard HRV indexes were extracted from the recordings. RESULTS: The log of very low-frequency (LnVLF) power, an index of HRV derived from power spectral analysis of the electrocardiogram signal (0.0033-0.04 Hz [in milliseconds squared]), was lower in the depressed than in the nondepressed patients (P<.001). There were 47 deaths (6.1%) during a 30-month follow-up. After adjusting for potential confounders, the depressed patients remained at higher risk for all-cause mortality compared with the nondepressed patients (hazard ratio, 2.8; 95% confidence interval [CI], 1.4-5.4; P<.003). When LnVLF power was entered into the model, the hazard ratio for depression dropped to 2.1 (95% CI, 1.1-4.2; P = .03). The proportion of the risk for depression attributable to LnVLF power was 0.27 (95% CI, 0.23-0.31; P<.001). CONCLUSIONS: Low HRV partially mediates the effect of depression on survival after acute MI. This finding helps to clarify the physiological mechanisms underlying depression's role as a risk factor for mortality in patients with coronary heart disease. It also raises the possibility that treatments that improve both depression and HRV might also improve survival in these patients.

Circadian and ultradian rhythms in heart rate variability.

AIM: Heart rate variability (HRV) patterns reflect the changing effect of sympathetic and parasympathetic modulation of the autonomic nervous system. While overall and circadian heart rate (HR) and HRV are well characterized by traditional measures, there is currently no method to measure ultradian cycles of HR and HRV. MATERIALS AND METHODS: HR/HRV for each 2-min interval was calculated using normal-to-normal interbeat intervals from overnight polysomnographic ECGs in 113 subjects, aged 58+/-10 years (65 male, 48 female). HR, SDNN2, high-frequency power (HF) and the LF (low-frequency power)/HF ratio were plotted. A curve-fitting algorithm, developed in MatLab, identified cyclic patterns of HR/HRV and extracted parameters to characterize them. Results were compared for older vs. younger patients, males vs. females, with vs. without severe sleep apnea, and for the upper and lower half of sleep efficiency. RESULTS: Ultradian patterns for different HR/HRV indices had variable correspondences with each other and none could be considered surrogates. Differences were seen for all comparison groups, but no one marker was consistently different across comparisons. CONCLUSION: Each HR/HRV parameter has its own rhythm, and the correspondence between these rhythms varies greatly across subjects. Quantification of ultradian patterns of HRV is feasible and could provide new insights into autonomic physiology.

Including patients with diabetes mellitus or coronary artery bypass grafting decreases the association between heart rate variability and mortality after myocardial infarction.

BACKGROUND: Decreased heart rate variability (HRV) is often assumed to be associated with mortality in all patients after myocardial infarction (MI), independent of clinical factors or time after MI. METHOD: HRV was determined from Holter tapes in the Cardiac Arrhythmia Suppression Trial (CAST). Patients were 71 +/- 120 days after MI. A total of 735 pre-therapy tapes were analyzed in patients who had ventricular premature contractions (VPCs) suppressed on the first treatment. The period of follow-up was 362 +/- 243 days (69 deaths). The association of clinical and demographic factors and 24-hour, daytime, and nighttime HRV to mortality in all patients, patients without coronary artery bypass graft (CABG) surgery between the qualifying MI and the Holter monitoring, and patients with neither CABG nor diabetes mellitus was determined with univariate Cox regression analysis. RESULTS: For the entire group and the subgroup without CABG, the strongest association was with increased daytime normalized high frequency power (NHF day). Further excluding patients with diabetes mellitus strengthened the association of HRV with mortality rate. Decreased natural logarithm (ln) 24-hour total and ultra low frequency (ULF) power were the strongest predictors of mortality. The best cutoff point for ln ULF for separating survivors and non-survivors was determined. After including a history of MI, congestive heart failure, or both as co-factors, ln ULF < or =7.85 identified patients at approximately 4-times the relative risk of mortality, but did not risk-stratify patients without prior MI or history of congestive heart failure. CONCLUSIONS: HRV predicts mortality rate in a broad range of times after MI. Excluding patients with CABG after MI or with diabetes mellitus significantly strengthens the association of HRV with mortality. HRV measures beyond the peri-infarction period, with clinical factors, can identify subgroups at an elevated risk of mortality.

Prediction of ventricular tachyarrhythmias by intracardiac repolarization variability analysis.

BACKGROUND: Arrhythmic sudden cardiac death (SCD) is generally mediated by ventricular fibrillation (VF) or fast ventricular tachycardia (FVT). We studied the predictive value of temporal QT variability detected from various sources of cardiac electric signal: surface ECG, far-field (FF), and near-field (NF) intracardiac electrograms (EGMs) in patients with implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS: Surface ECG and FF and NF intracardiac EGMs were simultaneously recorded at rest (mean heart rate, 74+/-15 bpm) for 4.5+/-1.3 minutes in 298 patients (mean age, 59+/-14; 216 male [73%]) with structural heart disease and an implanted Medtronic ICD for primary (231 patients, 78%) or secondary (67 patients, 22%) prevention of SCD. During mean follow-up of 16+/-8 months, 52 (13.1% per person-year of follow-up) patients sustained VT/VF and received appropriate ICD therapies, but only 19 (4.8% per person-year of follow-up) patients sustained FVT/VF with cycle length

Higher levels of inflammation factors and greater insulin resistance are independently associated with higher heart rate and lower heart rate variability in normoglycemic older individuals: the Cardiovascular Health Study.

OBJECTIVES: To explore the relationship between (1) insulin resistance and inflammation factors with (2) higher heart rate (HR) and lower heart rate variability (HRV) in normoglycemic older adults. DESIGN: Cross-sectional population-based study. PARTICIPANTS: Five hundred forty-five adults aged 65 and older with normoglycemia (fasting glucose <100 mg/dL) who participated in the Cardiovascular Health Study. MEASUREMENTS: Serum levels of three inflammation proteins (C-reactive protein (CRP), interleukin 6 (IL-6), and fibrinogen); insulin resistance, quantified according to the homeostasis assessment model (HOMA-IR); HR; and four representative measures of HRV (the standard deviation of normal beat to beat intervals (SDNN), the root mean square of successive differences (rMSSD), very low frequency power (VLF), and the low- to high-frequency power ratio (LF/HF)) derived from 24-hour Holter recordings. RESULTS: High CRP and IL-6 levels were associated with higher HR and lower SDNN and VLF after adjustment for multiple covariates, including HOMA-IR and clinical cardiovascular disease. High IL-6 was also associated with lower LF/HF. Significant univariate inverse relationships between HOMA-IR and HR and HRV were also found, but the strengths of these relationships were attenuated after adjustment for inflammation factors. CONCLUSION: Increased levels of inflammation markers and HOMA-IR are associated with higher HR and lower HRV. These findings suggest that inflammation may contribute to the pathogenesis of cardiovascular autonomic decline in older adults.

Circadian and ultradian rhythms in cardiac autonomic modulation.

UNLABELLED: Heart rate variability (HRV) patterns reflect the changing sympathetic and parasympathetic modulation of the autonomic nervous system. While overall and circadian heart rate (HR) and HRV are well characterized by traditional measures, ultradian cycles of HR and HRV are not. We have developed a method for capturing these rhythms during sleep and have now applied it to 24-hour recordings. METHODS: HR/HRV for each 2-min was calculated using normal-to-normal (NN) interbeat intervals from 24-hour Holter recordings in 10 healthy subjects, aged 26 +/- 2 yrs, 5M, 5F. HR, the standard deviation of NN intervals (SDNN2), high frequency power (HF) and the LF (low frequency power)/HF ratio were plotted. A curve-fitting algorithm, developed in MatLab, identified cyclic patterns of HR/HRV and extracted parameters to characterize them. Values were compared to those obtained in nighttime-only recordings in a set of 113 subjects, aged 58 +/- 10 yrs, 65M, 48F. RESULTS: Cyclic ultradian cycles were observed for each HR/HRV index. They had variable correspondences with each other and none could be considered surrogates. Although the number of cycles over 24 hours was greater, the mean cycle duration/number of cycles per hour was similar in both sets of recordings. CONCLUSIONS: Each HR/HRV parameter has its own rhythm, and the correspondence between these rhythms varies greatly across subjects. Although further studies are needed, it appears that there are intrinsic rhythms of autonomic modulation of HR on an scale of about 50 mins that persist during both the day and nighttimes. Quantification of ultradian patterns of HRV from 24-hour recordings is feasible and could provide new insights into autonomic physiology.

Sometimes higher heart rate variability is not better heart rate variability: results of graphical and nonlinear analyses.

OBJECTIVE: To determine the prevalence and effect on traditional heart rate variability (HRV) indices of abnormal HRV patterns in the elderly. METHODS: Hourly Poincaré plots and plots of spectral HRV from normal-to-normal interbeat intervals and hourly nonlinear HRV values were examined in a subset of 290 consecutive participants in the Cardiovascular Health Study. Only subjects in normal sinus rhythm with > or = 18 hours of usable data were included. Eligible subjects were 71 +/- 5 years. During 7 years of follow-up, 21.7% had died. Hours were scored as normal (0), borderline (0.5), or abnormal (1) from a combination of plot appearance and HRV. Summed scores were normalized to 100% to create an abnormality score (ABN). Short-term HRV versus each 5th percentile of ABN was plotted and a cutpoint for markedly increased HRV identified. The t-tests compared HRV for subjects above and below this cutpoint. Cox regression evaluated the association of ABN and mortality. RESULTS: Of 5,815 eligible hourly plots, 64.4% were normal, 14.5% borderline, and 21.1% abnormal. HR, SDNN, SDNNIDX, ln VLF and LF power, and power law slope did not differ by the cutpoint for increased short-term HRV, while SDANN and ln ULF power were significantly lower for those above the cutpoint. However, many HRV indices including LF/HF ratio and normalized LF and HF power were significantly different between groups (P < 0.001). Increased ABN was significantly associated with mortality (P = 0.019). Despite similar values for many HRV indices, being in the group above the cutpoint was significantly associated with mortality (P = 0.04). CONCLUSIONS: Abnormal HR patterns that elevate many HRV indices are prevalent among the elderly and associated with higher risk of mortality. Consideration of abnormal HRV may improve HRV-based risk stratification.

Traditional and nonlinear heart rate variability are each independently associated with mortality after myocardial infarction.

INTRODUCTION: Decreased heart rate variability (HRV) and abnormal nonlinear HRV shortly after myocardial infarction (MI) are risk factors for mortality. Traditional HRV predicts mortality in patients with a range of times post-MI, but the association of nonlinear HRV and outcome in this population is unknown. METHODS AND RESULTS: HRV was determined from 740 tapes recorded before antiarrhythmic therapy in Cardiac Arrhythmia Suppression Trial patients with ventricular premature contractions (VPCs) suppressed on the first randomized treatment. Patients were 70 +/- 121 days post-MI. Follow up was 362 +/- 241 days (70 deaths). The association between traditional time and frequency-domain HRV and mortality and nonlinear HRV and mortality were compared for the entire population (ALL), those without coronary artery bypass graft post-MI (no CABG), and those without CABG or diabetes (no CABG, no DIAB) using univariate and multivariate Cox regression analysis. Strength of association was compared by P values and Wald Chi-square values. Nonlinear HRV included short-term fractal scaling exponent, power law slope, and SD12 (Poincare dimension). For ALL and for no CABG, increased daytime SD12 had the strongest association with mortality (P=0.002 ALL and P <0.001 no CABG). For no CABG, no DIAB increased 24-hour SD12 hours had the strongest association (P <0.001) with mortality. Upon multivariate analysis, increased SD12, decreased ln ULF (ultra low frequency), and history of prior MI and history of congestive heart failure each remained in the model. CONCLUSION: Nonlinear HRV is associated with mortality post-MI. However, as with traditional HRV, this is diluted by CABG surgery post-MI and by diabetes. Results suggest that decreased long-term HRV and increased randomness of heart rate are each independent risk factors for mortality post-MI.

A simple method to identify sleep apnea using Holter recordings.

INTRODUCTION: Despite its severe cardiovascular and other consequences, sleep apnea syndrome frequently is undiagnosed. Because apneas result in repeated autonomic arousals associated with cyclic variations in heart rate (CVHR), we hypothesized that sleep apnea syndrome could be identified from simple HR tachograms (graphs of HR vs time) derived from ECG monitoring. METHODS AND RESULTS: HR tachograms were generated from 57 digitized ECGs (46 clinical patients undergoing diagnostic studies and 11 research subjects) obtained during overnight polysomnography. Thirty-three had significant sleep apnea syndrome (apnea-hypopnea index > or = 15). Eight patients had simultaneous Holter recordings during sleep studies (3 with digitized ECGs and 5 with paper ECGs). Duration of CVHR on tachograms was determined. CVHR patterns were characterized as high amplitude (HR changes > or = 20 beats/min per cycle) versus lower amplitude (6-19 beats/min per cycle); or regular (in frequency, amplitude, and morphology) versus irregular. Tachograms were classified as having visible HR changes versus not visible (flat). Twenty-four studies proved to be split-night, so CVHR was quantified for the first 3 hours of each study only. When subjects were dichotomized into shorter (< 20%, < 36 min) and longer (> or = 20%) durations of CVHR, longer CVHR had a positive predictive accuracy of 86% for significant sleep apnea syndrome and 100% for abnormal sleep. When flat tachograms were excluded, negative predictive accuracy for shorter CVHR was 100%. All patients (N = 13) with > 36 min high-amplitude CVHR had significant obstructive sleep apnea. All predictions from Holter-only data were concordant with clinical diagnoses. CONCLUSION: HR tachogram patterns derived from ambulatory ECGs provide a simple method for identifying sleep apnea syndrome and other sleep disturbances in patients without major autonomic dysfunction.

Autonomic nervous system responses during sedative infusions of dexmedetomidine.

BACKGROUND: The purpose of this study was to determine the effects of dexmedetomidine on systemic and cardiac autonomic reflex responses during rest and during thermal stress. METHODS: Volunteers received either placebo or low- or high-dose dexmedetomidine (target plasma concentrations 0.3 or 0.6 ng/ml, respectively) infusions in a prospectively randomized, double-blinded crossover study design. After 1 h, baroreflex sensitivity was assessed, and then core body temperature was raised to the sweating threshold and then lowered to the shivering threshold. Plasma catecholamines and blood pressure were measured, and cardiac autonomic responses were assessed by analysis of heart rate variability. RESULTS: Compared with placebo, plasma norepinephrine concentrations, blood pressure, heart rate, and some heart rate variability measures were lower after 1-h infusion of dexmedetomidine, but baroreflex responses did not differ significantly. Dexmedetomidine blunted the systemic and cardiac sympathetic effects of sweating observed during placebo infusion but had no effect on parasympathetic measures. Increases in blood pressure, and systemic catecholamines due to shivering were observed during placebo and dexmedetomidine, but these responses were less with dexmedetomidine. During shivering, dexmedetomidine infusion was associated with higher low-frequency and high-frequency heart rate variability power but lower heart rate compared with the sweating threshold and with the control period, suggesting nonreciprocal cardiac autonomic responses. CONCLUSIONS: Infusion of dexmedetomidine results in compensated reductions in systemic sympathetic tone without changes in baroreflex sensitivity. Dexmedetomidine blunts heart rate and the systemic sympathetic activation due to sweating, but it is less effective in blunting cardiac sympathetic responses to shivering. During dexmedetomidine infusion, cardiac sympathetic and parasympathetic tone may have nonreciprocal changes during shivering.