Economic evaluation of exercise-based cardiac rehabilitation in patients with a recent acute coronary syndrome.

Health care decision-making requires evidence of the cost-effectiveness of medical therapies. We evaluated the cost-effectiveness of exercise-based cardiac rehabilitation (ECR) implemented according to guidelines. All the patients (n = 204) had experienced a recent acute coronary syndrome and were randomized to a 1-year ECR (n = 109) or usual care (UC) group (n = 95). The patients' health-related quality of life was followed using the 15D instrument and health care costs were collected from electronic health registries. The cost-effectiveness of ECR was estimated based on intervention and health care costs and quality-adjusted life years (QALYs) gained. The total average cost per patient was lower in ECR than in UC. The incremental cost was divided by the baseline-adjusted incremental QALYs (0.045), yielding an incremental cost-effectiveness ratio of -€24511/QALYs. A combined endpoint of mortality, recurrent coronary event, or hospitalization for a heart failure occurred for five patients in ECR and 16 patients in UC (HR 3.9, 95% CI 1.4-10.6, P = 0.004, relative risk reduction 73%, number needed to treat eight). ECR is a dominant treatment option and decreases the occurrence of adverse cardiac events. These results are useful for decision-making when planning optimal utilization of resources in Finnish health care.

Autonomic Function Predicts Fitness Response to Short-Term High-Intensity Interval Training.

We tested the hypothesis that baseline cardiac autonomic function and its acute response to all-out interval exercise explains individual fitness responses to high-intensity interval training (HIT). Healthy middle-aged sedentary men performed HIT (n=12, 4-6×30 s of all-out cycling efforts with 4-min recovery) or aerobic training (AET, n=9, 40-60 min at 60% of peak workload in exercise test [Loadpeak]), comprising 6 sessions within 2 weeks. Low (LF) and high frequency (HF) power of R-R interval oscillation were analyzed from data recorded at supine and standing position (5+5 min) every morning during the intervention. A significant training effect (p< 0.001), without a training*group interaction, was observed in Loadpeak and peak oxygen consumption (VO2peak). Pre-training supine LF/HF ratio, an estimate of sympathovagal balance, correlated with training outcome in Loadpeak (Spearman's rho [rs]=-0.74, p=0.006) and VO2peak (rs=- 0.59, p=0.042) in the HIT but not the AET group. Also, the mean change in the standing LF/HF ratio in the morning after an acute HIT exercise during the 1(st) week of intervention correlated with training response in Loadpeak (rs=- 0.68, p=0.014) and VO2peak (rs=-0.60, p=0.039) with HIT but not with AET. In conclusion, pre-training cardiac sympathovagal balance and its initial alterations in response to acute HIT exercise were related to fitness responses to short-term HIT.

Temporal dynamics of the circadian heart rate following low and high volume exercise training in sedentary male subjects.

PURPOSE: Increased risk of arrhythmic events occurs at certain times during the circadian cycle with the highest risk being in the second and fourth quarter of the day. Exercise improves treatment outcome in individuals with cardiovascular disease. How different exercise protocols affect the circadian rhythm and the associated decrease in adverse cardiovascular risk over the circadian cycle has not been shown. METHODS: Fifty sedentary male participants were randomized into an 8-week high volume and moderate volume training and a control group. Heart rate was recorded using Polar Electronics and investigated with Cosinor analysis and by Poincaré plot derived features of SD1, SD2 and the complex correlation measure (CCM) at 1-h intervals over the 24-h period. RESULTS: Moderate exercise significantly increased vagal modulation and the temporal dynamics of the heart rate in the second quarter of the circadian cycle (p = 0.004 and p = 0.007 respectively). High volume exercise had a similar effect on vagal output (p = 0.003) and temporal dynamics (p = 0.003). Cosinor analysis confirms that the circadian heart rate displays a shift in the acrophage following moderate and high volume exercise from before waking (1st quarter) to after waking (2nd quarter of day). CONCLUSIONS: Our results suggest that exercise shifts vagal influence and increases temporal dynamics of the heart rate to the 2nd quarter of the day and suggest that this may be the underlying physiological change leading to a decrease in adverse arrhythmic events during this otherwise high-risk period.

Serum 25-hydroxyvitamin D is associated with major cardiovascular risk factors and cardiac structure and function in patients with coronary artery disease.

BACKGROUND AND AIMS: Vitamin D deficiency has been associated with increased risk for cardiovascular (CV) disease, but the possible effects of Vitamin D on cardiac structure and function are not well characterized. METHODS AND RESULTS: The correlation between 25-hydroxyvitamin D levels and metabolic and cardiac echocardiographic parameters was studied in ARTEMIS study population including 831diabetic and 659 non-diabetic patients with stable coronary artery disease (CAD). Low levels of Vitamin D were associated with high BMI (p < 0.001), high total and LDL cholesterol and triglyceride levels (p < 0.001 for all) in both diabetics and non-diabetics. Among non-diabetic patients, low Vitamin D was also associated independently with elevated systolic and diastolic blood pressure (p < 0.005). Low Vitamin D levels were independently associated with reduced left ventricular (LV) ejection fraction (p < 0.005) and increased left atrial diameter (p < 0.03) measured by cardiac ultrasound by 2-dimensional echo. In the non-diabetic group, low Vitamin D levels were associated with impaired LV filling (high E/E') (p < 0.03) and low E/A mitral flow pattern measured by Doppler echocardiography (p < 0.05). Among diabetics, low Vitamin D levels were also related to increased LV end-systolic diameter (p < 0.05) and right ventricular diameter (p < 0.005). The association between LV diastolic filling (E/E') and Vitamin D levels was significant (p < 0.01) after adjustment for the commonly recognized risk factors of diastolic dysfunction in linear regression analysis. CONCLUSIONS: Low Vitamin D is associated with several major cardiovascular risk factors and cardiac structural changes including impaired systolic and diastolic function, which together may explain the association of low Vitamin D to worse cardiovascular outcome.

Altered relationship between R-R interval and R-R interval variability in endurance athletes with overtraining syndrome.

Autonomic dysfunction decreases within-subject correlation between R-R interval length (RRi) and vagally mediated RRi variability in cardiac disease. We tested the hypothesis that overtraining syndrome (OTS) may also weaken this relationship. Nine OTS and 10 control endurance athletes underwent 24-h electrocardiogram monitoring, which was repeated in eight OTS and nine control athletes after 6 months, when two OTS athletes still had symptoms of OTS. The power of high-frequency (HF) oscillations of RRi was analyzed in 5-min epochs over the whole recording. Quadratic regression was performed between 5-min values of RRi and log-transformed (ln) HF to obtain R(2) for each recording. The relationship between RRi and HFln was higher in the OTS athletes than controls [R(2): 0.87 (90% confidence interval, CI: 0.84-0.89) vs 0.78 (90% CI: 0.72-0.84); P = 0.034; effect size = 1.22]. Large decrease in R(2) was observed in six recovered OTS athletes after 6 months follow-up [ΔR(2): -0.12 (90% CI: -0.25-0.01); P = 0.11; effect size = 1.44] with no changes in the controls. Mean values of RRi and its variability did not differ between the groups. The within-subject correlation between RRi and vagally mediated RRi variability was stronger in endurance athletes with OTS compared with controls. The present findings may improve the detection of OTS and recovery from OTS in endurance athletes.

Non-alpha-adrenergic effects on systemic vascular conductance during lower-body negative pressure, static exercise and muscle metaboreflex activation.

AIM: This study tested the hypothesis that non-α-adrenergic mechanisms contribute to systemic vascular conductance (SVC) in a reflex-specific manner during the sympathoexcitatory manoeuvres. METHODS: Twelve healthy subjects underwent lower-body negative pressure (LBNP, -40 mmHg) as well as static handgrip exercise (HG, 20% of maximal force) followed by post-exercise forearm circulatory occlusion (PECO, 5 min each) with and without α-adrenergic blockade induced by phentolamine (PHE). Aortic blood flow, finger blood pressure and superficial femoral artery blood flow were measured to calculate cardiac output, SVC and leg vascular conductance (LVC) during the last minute of each intervention. RESULTS: Mean arterial pressure (MAP) decreased more during LBNP with PHE compared with saline (-7 ± 7 vs. -2 ± 5%, P = 0.016). PHE did not alter the MAP response to HG (+20 ± 12 and +24 ± 16%, respectively, for PHE and saline) but decreased the change in MAP during PECO (+12 ± 7 vs. +21 ± 14%, P = 0.005). The decrease in SVC and LVC with LBNP did not differ between saline and PHE trials (-13 ± 10 vs. -17 ± 10%, respectively, for SVC, P = 0.379). In contrast, the SVC response to HG increased from -9 ± 12 with saline to + 5 ± 15% with PHE (P = 0.002) and from -16 ± 15 with saline to +1 ± 16% with PHE during PECO (P = 0.003). LVC responses to HG or PECO were not different from saline with PHE. CONCLUSIONS: Non-α-adrenergic vasoconstriction was present during LBNP. The systemic vasoconstriction during static exercise and isolated muscle metaboreflex activation, in the absence of leg vasoconstriction, was explained by an α-adrenergic mechanism. Therefore, non-α-adrenergic vasoconstriction is more emphasized during baroreflex, but not metaboreflex-mediated sympathetic activation.

Effect of cardiac vagal outflow on complexity and fractal correlation properties of heart rate dynamics.

1. Cardiac vagal outflow is the major factor determining the magnitude of heart rate (HR) variability analysed by traditional time and frequency domain methods. New analysis techniques, such as fractal and complexity methods, have been developed to probe non-linear features in HR behaviour that may not be detectable by traditional methods. 2. We investigated the effects of vagal blockade (glycopyrrolate i.v. 5 microg kg-1 h-1 for 2 h, n = 8 vs. unmedicated control group, n = 8) and various breathing patterns (n = 12) on two non-linear measures of HR variability--detrended fluctuation analysis (DFA) and approximate entropy (ApEn)--in healthy male volunteers. 3. Glycopyrrolate decreased the mean (+/-SD) ApEn from 1.46 +/- 0.18 to 0.85 +/- 0.24 (P = 0.001 in comparison with the control group), and increased the short-term (alpha 1) and intermediate-term (alpha 2) fractal scaling exponents of DFA, alpha 1 from 0.96 +/- 0.19 to 1.43 +/- 0.29 (P = 0.003) and alpha 2 from 1.13 +/- 0.10 to 1.34 +/- 0.14 (P < 0.001). 4. Decrease in fixed respiration rate from 15 to 6 breaths min-1 increased alpha 1 from 0.83 +/- 0.25 to 1.18 +/- 0.27 (P < 0.001), but decreased alpha 2 from 0.88 +/- 0.09 to 0.45 +/- 0.17 (P < 0.001) and ApEn from 1.26 +/- 0.12 to 1.10 +/- 0.14 (P = 0.028). Rapid breathing (24 min-1) had no influence on these non-linear measures of HR variability. Hyperventilation (15 min-1, tidal volume increased voluntarily by 0.5 l) decreased alpha 1 from 0.83 +/- 0.25 to 0.66 +/- 0.28 (P = 0.002) but did not affect alpha 2 or ApEn. 5. To conclude, vagal blockade alters the fractal scaling properties of R-R intervals (alpha 1, alpha 2) and reduces the complexity (ApEn) of HR behaviour. Both the fractal and complexity measures of HR variability can also be influenced by changes in the breathing pattern.

Effects of pharmacological adrenergic and vagal modulation on fractal heart rate dynamics.

Breakdown of short-term fractal-like behaviour of HR indicates an increased risk for adverse cardiovascular events and mortality, but the pathophysiological background for altered fractal HR dynamics is not known. Our aim was to study the effects of pharmacological modulation of autonomic function on fractal correlation properties of heart rate (HR) variability in healthy subjects. Short-term fractal scaling exponent (alpha1) along with spectral components of HR variability were analysed during the following pharmacological interventions in healthy subjects: (i) noradrenaline (NE) infusion (n=22), (ii) NE infusion after phentolamine (PHE) (n=8), (iii) combined NE + adrenaline (EPI) infusion (n=12), (iv) vagal blockade with high dose of atropine (n=10), (v) and vagal activation by low dose of atropine (n=10). Then alpha1 decreased progressively during the incremental doses of NE (from 0.85 +/- 0.250 to 0.55 +/- 0.23, P<0.0001). NE also decreased the average HR (P<0.001) and increased the high frequency spectral power (P<0.001). Vagal blockade with atropine increased the alpha1 value (from 0.82 +/- 0.22 to 1.24 +/- 0.41, P<0.05). Combined NE + EPI infusion and vagal activation with a low dose atropine did not result in any changes in alpha1, and alpha-adrenergic blockade by PHE did not completely reverse the effects of NE on alpha1. Increased levels of circulating NE result in reduction of short-term correlation properties of HR dynamics. The results suggest that coactivation of cardiac vagal outflow at the time of high levels of a circulating sympathetic transmitter explains the breakdown of fractal-like behaviour of human HR dynamics.

Time domain, geometrical and frequency domain analysis of cardiac vagal outflow: effects of various respiratory patterns.

The purpose of this study was to compare the applicability of four different measures of heart rate variability (HRV) in the assessment of cardiac vagal outflow, with special reference to the effect of breathing pattern. The anticholinergic effects of an intravenous glycopyrrolate infusion (5 microg x kg(-1) x h(-1) for 2 h) during spontaneous and controlled (15 min(-1)) breathing rate were investigated in eight volunteers, and the effects of different fixed breathing rates (6-15-24 min(-1)) and hyperventilation in 12 subjects. Cardiac vagal activity was assessed by ECG recordings in which the following measures of HRV were computed: the high-frequency (HF) spectral component, the instantaneous RR interval (RRI) variability (SD1) analysed from the Poincaré plots, the percentage of differences between successive RRIs greater than 50 ms (pNN50), and the square root of the mean squared differences of successive RRIs (RMSSD). On average, glycopyrrolate reduced the HF spectral component by 99.8%, SD1 by 91.3%, pNN50 by 100% and RMSSD by 97.0%. The change of breathing pattern from controlled to spontaneous decreased significantly the HF component and pNN50, but did not affect SD1 or RMSSD. Rapid breathing rate (24 min(-1)) decreased the HF component, but had no effects on the other measures. A controlled breathing rate is needed for a reliable assessment of cardiac vagal outflow by the spectral analysis technique. The quantitative geometrical analysis of short-term RRI variability from the Poincaré plots and the time domain measure RMSSD were not significantly affected by changes in the breathing rate, suggesting that these indices are more suitable for the measurement of cardiac vagal outflow during the 'free-running' ambulatory conditions.

Changes in cardiac autonomic regulation after prolonged maximal exercise.

Harmful cardiac events occurs frequently after exercise. However, the cardiac autonomic regulation after vigorous exercise is not well known. This study was designed to assess heart rate (HR) variability before and after a 75 km cross-country skiing race. HR variability was assessed by using standard statistical measures along with spectral and quantitative Poincarè plot analysis of HR variability in 10 healthy male subjects (age 36 +/- 11 years). The average HR was at the same level 1 day after the race as before the race, but on the second day, HR was significantly lower (P<0.001) compared with the prerace and 1 day after values. The normalized high-frequency (HF) spectral component of HR variability (nuHF) was lower (P<0.01) on the first day after the maximal exercise compared with the pre-exercise values but returned to or even exceeded the prerace level on the second day (P<0.01). The changes in short-term R-R interval variability analysed from the Poincaré plot were similar to those observed in the HF spectral component. The normalized low-frequency (LF) spectral component of HR variability (nuLF) was higher (P<0.01) on the first day after the exercise compared with the prerace levels and it also returned to the pre-exercise level or even dropped below it on the second day after the race. The mean time it took the HF spectral component to return to the pre-exercise level was 4.2 +/- 4.2 h (ranging from 0 to 12 h). This recovery time correlated inversely with the maximal oxygen consumption (VO2max) measured during the bicycle exercise test before the skiing race (r=-0.712, P<0.016). The cardiac vagal outflow is blunted for several hours after prolonged vigorous exercise. The recovery time of reduced vagal outflow depends on individual cardiorespiratory fitness and there is an accentuated rebound of altered autonomic regulation on the second day after prolonged exercise.

Effects of exercise and passive head-up tilt on fractal and complexity properties of heart rate dynamics.

tk;1Passive head-up tilt and exercise result in specific changes in the spectral characteristics of heart rate (HR) variability as a result of reduced vagal and enhanced sympathetic outflow. Recently analytic methods based on nonlinear system theory have been developed to characterize the nonlinear features in HR dynamics. This study was designed to assess the changes in the fractal and complexity measures of HR behavior during the passive head-up tilt and during exercise. Fractal exponent (alpha(1)) and approximate entropy (ApEn), measures of short-term correlation properties and overall complexity of HR, respectively, along with spectral components of HR variability were analyzed during a passive head-up tilt test (n = 10) and a low-intensity steady-state exercise (n = 20) in healthy subjects. We observed that alpha(1) increased during the tilt test (from 0.85 +/- 0.22 to 1.48 +/- 0.20; P < 0.001) and during the exercise (from 1.00 +/- 0.22 to 1.37 +/- 0. 14; P < 0.001). ApEn also increased during the exercise (from 1.04 +/- 0.11 to 1. 11 +/- 0.08; P < 0.05), but it did not change during the tilt test. The normalized high-frequency spectral component decreased and the low-frequency component increased similarly during both the exercise and the tilt test (P < 0.001 for all). Exercise and passive tilt result in an increase of short-term fractal correlation properties of HR dynamics, which is related to changes in the balance between the low- and high-frequency oscillations in controlled situations. Overall complexity of HR dynamics increases during exercise but not during passive tilt.

Differences in autonomic modulation of heart rate during arm and leg exercise.

Heart rate (HR) is higher during dynamic arm exercise than during leg exercise at equal oxygen consumption levels, but the physiological background for this difference is not completely understood. The vagally mediated beat-to-beat R-R interval fluctuation decreases until the level of approximately 50% of maximal oxygen consumption during an incremental bicycle exercise, but the vagal responses to arm exercise are not well known. Changes in autonomic modulation of HR were compared during arm and leg exercise by measuring beat-to-beat R-R interval variability from a Poincaré plot normalized for the average R-R interval (SD1n), a measure of vagal activity, in 14 healthy male subjects (age 20 +/- 4 years) who performed graded bicycle and arm cranking tests until exhaustion. Seven of the subjects also performed the dynamic arm and leg tests after beta-adrenergic blockade (propranolol 0.2 mg kg-1 i.v.). More rapid reduction occurred in SD1n during the low-intensity level of dynamic arm exercise than during dynamic leg exercise without beta-blockade (e.g. 11 +/- 6 vs. 20 +/- 10 at the oxygen consumption level of 1.2 l min-1; P < 0.001) and with beta-blockade (e.g. 13 +/- 4 vs. 25 +/- 10 at the level of 1.0 l min-1; P < 0.05), and the mean HR was significantly higher during submaximal arm work than during leg work in both cases (e.g. during beta-blockade 81 +/- 12 vs. 74 +/- 6 beats min-1 at the level of 1.0 l min-1; P < 0.05). These data show that dynamic arm exercise results in more rapid withdrawal of vagal outflow than dynamic leg exercise.

Heart rate dynamics before spontaneous onset of ventricular fibrillation in patients with healed myocardial infarcts.

The traditional methods of analyzing heart rate (HR) variability have failed to predict imminent ventricular fibrillation (VF). We sought to determine whether new methods of analyzing RR interval variability based on nonlinear dynamics and fractal analysis may help to detect subtle abnormalities in RR interval behavior before the onset of life-threatening arrhythmias. RR interval dynamics were analyzed from 24-hour Holter recordings of 15 patients who experienced VF during electrocardiographic recording. Thirty patients without spontaneous or inducible arrhythmia events served as a control group in this retrospective case control study. Conventional time- and frequency-domain measurements, the short-term fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and the slope (beta) of the power-law regression line (log power - log frequency, 10(-4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in the patients before the onset of VF than in the control patients, but the SD and the low-frequency spectral components of RR intervals did not differ between the groups. The short-term scaling exponent performed better than any other measurement of HR variability in differentiating between the patients with VF and controls. Altered fractal correlation properties of HR behavior precede the spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may help to identify abnormalities in HR behavior before VF.

Heart rate dynamics during accentuated sympathovagal interaction.

Concomitant sympathetic and vagal activation can occur in various physiological conditions, but there is limited information on heart rate (HR) behavior during the accentuated sympathovagal antagonism. Beat-to-beat HR and blood pressure were recorded during intravenous infusion of incremental doses of norepinephrine in 18 healthy male volunteers (mean age 23 +/- 5 yr). HR and blood pressure spectra and two-dimensional Poincaré plots were generated from the baseline recordings and from the recordings at different doses of norepinephrine. The mean blood pressure increased (from 90 +/- 7 to 120 +/- 9 mmHg, P < 0.001), HR decreased (from 60 +/- 9 to 48 +/- 7 beats/min, P < 0.001), and the high-frequency spectral component of HR variability increased (P < 0.001) during the norepinephrine infusion as evidence of accentuated sympathovagal interaction. Abrupt aperiodic changes in sinus intervals that were not related to respiratory cycles or changes in blood pressure occurred in 14 of 18 subjects during the norepinephrine infusions. These fluctuations in sinus intervals resulted in a complex or parabola-shaped structure of the Poincaré plots of successive R-R intervals and a widening of the high-frequency spectral peak. In four subjects, the abrupt fluctuations in sinus intervals were followed by a sudden onset of fixed R-R interval dynamics with a loss of respiratory modulation of HR, resulting in a torpedo-shaped structure of the Poincaré plots. These data show that HR behavior becomes remarkably unstable during accentuated sympathovagal interaction, resembling stochastic dynamics or deterministic chaotic behavior. These features of HR dynamics can be better identified by dynamic analysis of beat-to-beat behavior of R-R intervals than by traditional analysis techniques of HR variability.

Vagal modulation of heart rate during exercise: effects of age and physical fitness.

This study was designed to assess the effects of age and physical fitness on vagal modulation of heart rate (HR) during exercise by analyzing the instantaneous R-R interval variability from Poincaré plots (SD1) at rest and at different phases of a bicycle exercise test in a population of healthy males. SD1 normalized for the average R-R interval (SD1n), a measure of vagal activity, was compared at rest and during exercise among subjects of ages 24-34 (young, n = 25), 35-46 (middle-aged, n = 30), and 47-64 yr (old, n = 25) matched for peak O2 consumption (VO2 peak) and among subjects with VO2 peak of 28-37 (poor, n = 25), 38-45 (average, n = 36), and 46-60 ml.kg-1.min-1 (good, n = 25) matched for age. SD1n was higher at rest in the young subjects than in the middle-aged or old subjects (39 +/- 14, 27 +/- 16, and 21 +/- 8, respectively; P < 0.001), but the age-related differences in SD1n were smaller during exercise [e.g., 11 +/- 5, 9 +/- 5, and 8 +/- 4 at the level of 100 W; P = not significant (NS)]. The age-matched subjects with good, average, and poor VO2 peak showed no difference in SD1n at rest (32 +/- 17, 28 +/- 13, and 26 +/- 11, respectively; P = NS), but SD1n differed significantly among the groups from a low to a moderate exercise intensity level (e.g., 13 +/- 6, 10 +/- 5, and 6 +/- 3 for good, average, and poor fitness groups, respectively; P < 0.001, 100 W). These data show that poor physical fitness is associated with an impairment of cardiac vagal function during exercise, whereas aging itself results in more evident impairment of vagal function at rest.

Dynamic analysis of heart rate may predict subsequent ventricular tachycardia after myocardial infarction.

Dynamics analysis of RR interval behavior and traditional measures of heart rate variability were compared between postinfarction patients with and without vulnerability to ventricular tachyarrhythmias in a case-control study. Short-term fractal correlation of heart rate dynamics was better than traditional measures of heart rate variability in differentiating patients with and without life-threatening arrhythmias.

Quantitative beat-to-beat analysis of heart rate dynamics during exercise.

Beat-to-beat heart rate (HR) dynamics were studied by plotting each R-R interval as a function of the previous R-R interval (Poincaré plot) during incremental doses of atropine followed by exercise for 10 subjects and during exercise without autonomic blockade for 31 subjects. A quantitative two-dimensional vector analysis of a Poincaré plot was used by measuring separately the standard deviation of instantaneous beat-to-beat R-R interval variability (SD1) and the standard deviation of continuous long-term R-R interval variability (SD2) as well as the SD1/SD2 ratio. Quantitative Poincaré measures were compared with linear measures of HR variability (HRV) and with approximate entropy (ApEn) at rest and during exercise. A linear progressive reduction was observed in SD1 during atropine administration, and it remained almost at the zero level during exercise after a parasympathetic blockade. Atropine resulted in more variable changes in SD2 and the SD1/SD2 ratio, but during exercise after parasympathetic blockade, a progressive increase was observed in the SD1/SD2 ratio until the end of exercise. The SD1/SD2 ratio had no significant correlations with the frequency domain measures of HRV. However, the SD1/SD2 ratio had a modest correlation with ApEn at rest (r = -0.69, P < 0.001), but not during exercise (r = 0.27, P = NS). All measures of vagal modulation of HR decreased progressively until the ventilatory threshold level was reached, when sympathetic activation was reflected as changes in the SD1/SD2 ratio. These results show that quantitative two-dimensional vector analysis of a Poincaré plot can provide useful information on vagal modulation of R-R interval dynamics during exercise that are not easily detected by linear summary measures of HRV or by ApEn.