Slower Heart Rate Recovery Research Articles

P1511Promising prognostic value of negative stress echocardiography in patients with incomplete revascularization after successful primary PCI

Abstract Background The specific role of non-invasive functional testing in a risk stratification of patients with incomplete revascularization after primary percutaneous coronary intervention (pPCI) still needs to be evaluated. The aim of our study was to assess negative prognostic value of stress echocardiography (SECHO) after successful pPCI and incomplete revascularization of non-culprit lesions. Methods Our study consisted of 202 patients (mean age 59±10 years, male 142) successfully treated with pPCI, who performed SECHO according to Bruce protocol in order to assess residual ischemia in coronary artery with non-culprit lesion. Duke treadmill score, functional capacity (Metabolic Equivalents - METs), achieved target heart rate (THR), heart rate recovery (HRR), wall motion score index (WMSI) and ejection fraction were interrogated in all patients. Slow HRR was defined as ≤18 beats/min. Median follow-up of the patients was 70 months (IQR 55–83 months) for the occurrence of cardiovascular death and non-fatal myocardial infarction. We also assessed the independent predictors for the occurrence of the adverse events. Results Out of 202 patients, 42 (20.8%) had positive SECHO test, 4 patients (1.98%) had died due to non-cardiac causes and 7 patients (3.5%) were lost to follow-up. From the remaining 149 patients with negative SECHO, 13 (8.7%) had an adverse event (7 cardiovascular deaths and 6 non-fatal MI). Negative predictive value of SECHO test was 91.3%. Univariate predictors of adverse events were slow HRR (HR 4.343 [95% CI 1.473–14.011], p=0.008), and not achieved THR (HR 0.322 [95% CI 0.105–0.985], p=0.047). By multivariate analysis, only slow HRR remained independent predictor of adverse events (HR 3.324 [95% CI 1.013–10.906], p=0.048). Conclusion SECHO test has excellent negative prognostic value in patients with incomplete revascularization of non-culprit lesions after successful pPCI. Still, particular care should be taken to the patients with slow HRR and negative SECHO due to increased risk for the occurrence of adverse events. Acknowledgement/Funding Ministry of Education and Science of the Republic of Serbia (Grant No III41022)

Reproducibility of post-exercise heart rate recovery indices: A systematic review

Heart rate recovery (HRR) has been widely used to evaluate the integrity of the autonomic nervous system with a slower HRR being associated with greater cardiovascular risk. Different HRR indices have been proposed. Some evaluate HR changes from the end of exercise to a specific recovery moment (e.g. 60s - HRR60s; 120s - HRR120s; 300s - HRR300s) and others calculate time-constant decays of HR for different recovery intervals (e.g. first 30s - T30; the entire period - HRRt). Several studies have examined the reproducibility of these commonly-used HRR indices, but reported discordant findings. Thus, this systematic review was designed to synthesize the reproducibility of HRR. We included studies that evaluated short-term (<1 year) reproducibility of HRR after dynamic exercise by employing typical measures of reliability (intraclass correlation coefficient, ICC) and agreement (coefficient of variation, CV). The electronic database PubMed/Medline was searched for relevant studies published up to July 2018. From the initial 120 records identified, 15 studies were retained for the qualitative synthesis of 24 experimental conditions. During most experimental conditions, high ICC and desirable CV were reported for HRR60s (62.5 and 76.2%, respectively), HRR120s (55.6 and 71.4%) and HRR300s (50.0 and 100.0%). While, it were reported during the minority of conditions for HRRt (37.5 and 42.9%) and in none condition for T30 (0.0 and 0.0%). In conclusion, HRR60s, HRR120s and HRR300s exhibited good reproducibility for evaluating HRR in predominantly healthy males within research and clinical settings. In contrast, caution should be taken when employing other HRR indices (T30, HRRt) due to their poorer reproducibility.

Slow Heart Rate Recovery Is Associated with Increased Exercise-induced Arterial Stiffness in Normotensive Patients without Overt Atherosclerosis.

BACKGROUNDThis study evaluated whether blunted autonomic activity as measured by heart rate recovery (HRR) was associated with increased arterial stiffness, especially increased exercise-induced arterial stiffness, in normotensive patients without overt atherosclerosis.METHODSOne hundred fifty-four normotensive patients without overt atherosclerosis who had undergone a treadmill exercise test were consecutively enrolled. HRR was measured at one minute after exercise. Brachial-ankle pulse wave velocity (baPWV) at rest was measured, and carotid arterial stiffness indices at rest (CSI at rest) and after exercise (CSI after exercise) were assessed.RESULTSPatients with slow HRR were older and tended to be male, and they had diabetes, higher resting and peak systolic blood pressures, higher resting heart rate, lower peak heart rate, lower metabolic equivalents, increased baPWV, and increased CSIs at rest and after exercise. HRR was inversely associated with baPWV and CSI after exercise when established cardiovascular risk factors were adjusted as confounding factors, and HRR was associated with CSI after exercise when resting systolic blood pressure and metabolic equivalent of tasks on cardiovascular risk factors were added as confounding factors.CONCLUSIONSSympathovagal imbalance demonstrated by slow HRR was associated with increased arterial stiffness and, above all, was closely associated with exercise-induced arterial stiffness in normotensive patients without overt atherosclerosis. This phenomenon might have been observed because blunt carotid arterial vasomotion following exercise results from autonomic dysfunction as well as vascular endothelial dysfunction.

Heart rate recovery as a sensitive indicator of physical activity changes in perimenopausal and postmenopausal women

Heart rate recovery (HRR), which is defined as the rate of heart rate decline after cessation of exercise, is an important indicator of exercise tolerance. The aim of this study was to investigate the effect of a 4-month moderate reduction in physical activity on pre-exercise and exercise heart rate (HR) as well as HRR after exercise cessation in perimenopausal and postmenopausal women. 10 physically active females, 62.5±3.0 years old, participated in this study. They performed an 8-min constant power output (~50W) cycling exercise at an intensity corresponding to about 65% of maximal heart rate. Heart rate was measured continuously starting from 1 minute before exercise, during the exercise test and 3 min after exercise cessation. Furthermore, before and after exercise, blood pressure (BP) and tympanic temperature (Tt) were measured. The exercise test was performed twice, before and after a 4-month reduction in physical activity. 4 months of the slight reduction in physical activity (by ~16%) did not cause any changes in pre-exercise and exercise HR, however, significantly higher HR during the 1st min after exercise (p=0.03), as well slower HRR (p=0.03), were reported. No effects of the reduction in physical activity were observed in resting and post-exercise BP and Tt. Even a slight reduction in physical activity is accompanied by a lower rate of HRR , which indicates a decrease in exercise tolerance. These results indicate that HRR is a sensitive indicator of physical capacity also in peri- and postmenopausal women, since the changes in HRR in response to physical activity level occur earlier than changes in pre-exercise and exercise heart rate. heart rate, heart rate recovery, physical activity in the elderly

Autonomic nervous system dysfunction and abnormal heart rate recovery

The nervous autonomic system imbalance with a shift towards a sympathetic predominance is associated with an overall increased cardiovascular risk by elevated heart pressure, tachycardia and arrhythmias. Heart rate recovery (HRR) immediately after stopping the exercise stress test is considered as a reflection of the equilibrium between sympathetic and parasympathetic tone, focusing upon vagal reactivation. The aim of this study was to evaluate HRR after ergometer exercise testing as a marker of impaired autonomic balance and the possible correlation between a slow HRR and cardiovascular risk factors (smoking, diabetes, age, hypertension). We performed a retrospective analysis on 31 patients with abnormal heart rate recovery studying the possible influence of the most important cardiovascular risk factors: smoking, diabetes, obesity and hypertension as possible determinants for autonomic imbalance. There was no association found between the presence of the major risk factors with the DHR1, which only seems to be correlated with the maximal load of the stress test. When defining sub-groups with lower cut-off values for HRR and taking into consideration only the segment of age above 75, we have obtained several correlations with smoking status, diastolic blood pressure and obesity. Age is probably the most important determinant in our analysis, the older the patient the slower he will recover from the 3rd minute: smoking patients over 75–80 will have slower HRR from minute 2 and they will be less capable to reach higher maximal loads ( Table 1 , Fig. 1 ). Even though our study group is small, our findings still raise the question if we should be more strict when considering the HRR abnormality with a possible cut-off value of 8/9 for each of the minutes of recovery.

Deterioration of Chronotropic Responses and Heart Rate Recovery Indices in Men With Erectile Dysfunction.

IntroductionErectile dysfunction (ED) and cardiovascular (CV) diseases share common risk factors and ED has been accepted as an early manifestation of CV disease. Exercise stress testing (EST) is used to evaluate CV functions in men with ED. Low exercise workload, a slower heart rate recovery (HRR) after exercise, and inability to increase heart rate during EST (chronotropic incompetence) are independent negative predictors of adverse CV outcomes.AimTo assess the association among EST parameters, ED, and testosterone levels.MethodsThe study population consisted of 41 patients with ED and 40 controls. All participants underwent treadmill EST to assess cardiac autonomic functions. HRR indices were calculated by subtracting 1st (HRR1), 2nd (HRR2), and 3rd (HRR3) minute heart rates during the recovery period from maximal heart rate. Total exercise duration, exercise capacity and chronotropic response, and plasma testosterone levels were evaluated. Erectile functions were evaluated with the Sexual Health Inventory for Men. Patients were divided into subgroups according to severity and duration of ED.Main Outcome MeasuresMean HRR1 (30.6 ± 11.9 vs 36.9 ± 9.9; P = .01), HRR2 (44.9 ± 12.4 vs 54.9 ± 7.8; P < .001), and HRR3 (50.1 ± 11.7 vs 63.0 ± 7.9; P < .001) were significantly lower in the ED than in the control group. Total exercise duration (9.4 ± 1.9 vs 10.9 ± 1.7 minutes; P < .001), exercise capacity (12.5 ± 1.9 vs 13.6 ± 1.4 metabolic equivalents; P = .004), and chronotropic response (0.88 ± 0.1 vs 1.0 ± 0.1; P < .001) were worse in the ED group. However, we found no association between severity and duration of ED and EST parameters. In addition, serum testosterone levels were significantly correlated with HRR1 (r = 0.36, P = .02) in men with ED.ConclusionOur data suggested that cardiac autonomic functions are impaired in patients with ED. A weak correlation between cardiac autonomic dysfunction and low testosterone levels in patients with ED was noted. However, further studies are needed to elucidate the prognostic significance and clinical implications of impaired autonomic functions and testosterone replacement therapy in patients with ED.Kucukdurmaz F, Agar G, Resim S. Deterioration of Chronotropic Responses and Heart Rate Recovery Indices in Men With Erectile Dysfunction. Sex Med 2018;6:8–14.

Heart Rate Recovery and Cancer Risk: Prospective Cohort Study.

This study aims to determine the association between 2-minute heart rate recovery (HRR) and cancer risk. Each participant (5379 women; 8485 men) provided HRR obtained from treadmill tests. The outcome was site-specific cancer. Over 9 years of follow-up, 630 cancer events (258 women) were accrued. Slower HRR was associated with increased thyroid cancer risk in women ( P for trend = .0121) and colorectal cancer risk in men ( P for trend = .0034). The lowest HRR (<13 bpm) had higher hazards of thyroid cancer (hazard ratio [HR] = 2.20; 95% CI = 1.28-3.77) in women and colorectal cancer (HR = 3.08; 95% CI = 1.32-7.15) in men. In women, slower HRR and lower proportions of heart rate recovery (PHRR) were associated with higher hazards of thyroid cancer in women and metabolically related cancers (liver and colorectal) in men. Slower HRR and lower PHRR were independent risk factors for thyroid cancer in women and metabolically related cancers in men.

Cardiac Autonomic Modulation and the Kinetics of Heart Rate Responses in the On- and Off-Transient during Exercise in Women with Metabolic Syndrome.

Objective: To test whether women with metabolic syndrome (MS) have impairments in the on- and off-transients during an incremental test and to study whether any of the MS components are independently associated with the observed responses.Research Design and Methods: Thirty-six women aged 35–55 years were divided into a group with MS (MSG, n = 19) and a control group (CG, n = 17). R-R intervals (RRi) and heart rate variability (HRV) were calculated on a beat-to-beat basis and the heart rate (HR) at the on- and off-transient were analyzed during an incremental cardiopulmonary exercise test (CPET).Results: MSG showed lower aerobic capacity and lower parasympathetic cardiac modulation at rest compared with CG. HR values in on-transient phase were significantly lower in MSG compared with CG. The exponential amplitudes “amp” and the parameters “τ” [speed of heart rate recovery (HRR)] were lower in MSG. MSG exhibited higher HR values in comparison to CG during the off-transient indicating a slower HRR. In MSG, there was an inverse and significant correlation between fasting plasma vs. ΔF and glucose vs. exponential “τ” of HRR dynamics.Conclusion: MS is associated with poor heart rate kinetics. The altered HR kinetics seems to be related to alterations in cardiac parasympathetic modulation, and glucose metabolism seems to be the major determinant.

Hemodynamic and autonomic responses after a single session of resistance exercise following anodal motor cortex tDCS

BACKGROUND: Transcranial direct current stimulation (tDCS) seems to modulate cardiac autonomic function and blood pressure (BP) at rest and during exercise. Therefore, it is possible that anodal tDCS could influence post-exercise hypotension. OBJECTIVE: To investigate whether anodal tDCS applied over the motor cortex would affect cardiac autonomic modulation and BP after resistance exercise. METHODS: Twelve apparently healthy young men performed two experimental sessions: anodal tDCS or sham condition followed by resistance exercise. Blood pressure (BP), heart rate (HR), rate-pressure product (RPP), and HR variability (HRV) were obtained before and during post-exercise recovery (at 20 and 60 minutes). RESULTS: Compared to pre-exercise, systolic BP decreased at 20 and at 60 minutes of post-exercise recovery only in anodal tDCS condition (p = 0.03), with no statistical differences in sham condition (p > 0.05). Diastolic and mean BP reduced after both anodal tDCS and sham conditions with no differences between them (P> 0.05). In comparison with anodal tDCS, there were slower HR recovery (tDCS vs. sham: -2 ± 14 vs. 14 ± 8 bpm) and higher RPP (tDCS vs. sham: -1083 ± 1846 vs. 1672 ± 1275 mmHg × bpm) after exercise following sham condition (P 0.05). CONCLUSION: A single session of primary motor cortex tDCS is capable of decreasing the systolic BP and HR responses, as well as the cardiac work after a resistance exercise session in young normotensive subjects regardless of any changes in cardiac autonomic modulation.

Increased interarm blood pressure difference is associated with autonomic dysfunction and atherosclerosis in patients with chest pain and no history of coronary artery disease

ObjectivesInterarm blood pressure (BP) difference has been reported to be associated with atherosclerosis and increased cardiovascular death. We were to investigate associations of interarm systolic blood pressure (SBP) difference with heart rate recovery (HRR) after exercise, an index of autonomic function, and carotid atherosclerotic markers, and to evaluate the association of interarm SBP difference with concurrent coronary artery disease (CAD). MethodsA total of 995 consecutive patients who underwent treadmill stress echocardiography with chest pain but no history of CAD were enrolled. Interarm SBP difference, carotid intima-media thickness (IMT) and plaque were measured before exercise, and HRR 2min following exercise was assessed. Suspected CAD was defined as newly developed wall motion abnormalities after treadmill exercise. ResultsPatients with an interarm SBP difference≥10mmHg had higher prevalence of hypertension, increased right and left SBP, right diastolic BP, mean arterial pressure, body mass index and carotid IMT, existent carotid plaque, lower metabolic equivalents and slower HRR. Interarm SBP difference≥10mmHg was independently associated with slower HRR and existent carotid plaque. Suspected CAD was associated with existent carotid plaque or slower HRR, but not with an interarm SBP difference≥10mmHg. ConclusionsIncreased interarm SBP difference was associated with lower autonomic modulation and carotid atherosclerosis in patients with chest pain and no history of CAD, but not with suspected CAD. Observed adverse prognosis in patients with increased interarm BP difference might result from long-term persistent autonomic dysfunction and atherosclerosis.

255 - Deterioration of chronotropic responses and heart rate recovery indices in men with erectile dysfunction

Abstract Introduction Erectile dysfunction (ED) and cardiovascular (CV) diseases share common risk factors and ED has been accepted as an early manifestation of CV disease. Exercise stress testing (EST) is used to evaluate CV functions in men with ED. Low exercise workload, a slower heart rate recovery (HRR) after exercise, and inability to increase heart rate during EST (chronotropic incompetence) are independent negative predictors of adverse CV outcomes. Aim To assess the association among EST parameters, ED, and testosterone levels. Methods The study population consisted of 41 patients with ED and 40 controls. All participants underwent treadmill EST to assess cardiac autonomic functions. HRR indices were calculated by subtracting 1st (HRR1), 2nd (HRR2), and 3rd (HRR3) minute heart rates during the recovery period from maximal heart rate. Total exercise duration, exercise capacity and chronotropic response, and plasma testosterone levels were evaluated. Erectile functions were evaluated with the Sexual Health Inventory for Men. Patients were divided into subgroups according to severity and duration of ED. Main Outcome Measures Mean HRR1 (30.6 ± 11.9 vs 36.9 ± 9.9; P = .01), HRR2 (44.9 ± 12.4 vs 54.9 ± 7.8; P P P P = .004), and chronotropic response (0.88 ± 0.1 vs 1.0 ± 0.1; P P = .02) in men with ED. Conclusion Our data suggested that cardiac autonomic functions are impaired in patients with ED. A weak correlation between cardiac autonomic dysfunction and low testosterone levels in patients with ED was noted. However, further studies are needed to elucidate the prognostic significance and clinical implications of impaired autonomic functions and testosterone replacement therapy in patients with ED. Kucukdurmaz F, Agar G, Resim S. Deterioration of Chronotropic Responses and Heart Rate Recovery Indices in Men With Erectile Dysfunction. Sex Med 2018;6:8–14.

Relation of heart rate recovery after exercise testing to coronary artery calcification

Background: We examined whether slow heart rate recovery (HRR) after exercise testing as an estimate of impaired autonomic function is related to coronary artery calcification (CAC), an emerging marker of coronary atherosclerosis.Methods: We evaluated 2088 men who participated in a health-screening program that included measures of CAC and peak or symptom-limited cardiopulmonary exercise testing. HRR was calculated as the difference between peak heart rate (HR) during exercise testing and the HR at 2 min of recovery after peak exercise. We measured CAC using multidetector computed tomography to calculate the Agatston coronary artery calcium score. Advanced CAC was defined as a mean CAC >75th percentile for each age group.Results: HRR was negatively correlated with CAC (r = −.14, p < .01). After adjusting for conventional risk factors, participants in the lowest quartile of HRR (<38 bpm) were 1.59 times (95% CI: 1.17–2.18; p < .05) more likely to have advanced CAC than their counterparts in the highest quartile of HRR (>52 bpm). Each 1 bpm decrease in HRR was associated with 1% increase in advanced CAC after adjusting for potential confounders.Conclusions: An attenuated HRR after exercise testing is associated with advanced CAC, independent of coronary risk factors and other related hemodynamic response.KEY MESSAGESSlow heart rate recovery (HRR) after maximal exercise testing, indicating decreased autonomic function, is associated with an increased risk of cardiovascular event and mortality.Slow HRR has been linked with the occurrence of malignant ventricular arrhythmias, but it remains unclear whether slow HRR is associated with an increased risk of coronary artery calcification (CAC), an emerging marker of coronary atherosclerosis.An attenuated HRR after exercise testing was associated with advanced CAC, independent of coronary risk factors and other potential hemodynamic confounder, supporting the hypothesis that slow HRR is related to the burden of atherosclerotic coronary artery disease.

Predictors of Long-Term Outcomes in Asymptomatic Patients With Severe Aortic Stenosis and Preserved Left Ventricular Systolic Function Undergoing Exercise Echocardiography.

In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess incremental prognostic utility of exercise stress echocardiography. We studied 533 such patients (age, 66±13 years; 78% men; 31% with coronary artery disease) who underwent exercise stress echocardiography between 2001 and 2012. Clinical, echocardiographic, and exercise variables (metabolic equivalents [METs], % of age-sex-predicted METs and heart rate recovery at first minute post exercise) were recorded. The end point was all-cause mortality. The Society of Thoracic Surgeons score, left ventricular ejection fraction, mean resting aortic valve (AV) gradient, indexed AV area, METs, and heart rate recovery were 2.9±3%, 58±4%, 35±11 mm Hg, 0.47±0.1 cm(2)/m(2), 7.8±3, and 26±12 bpm, respectively. Only 50% achieved >100%, whereas 26% achieved <85% age-sex-predicted METs. There were no major exercise stress echocardiography-related complications. Over 6.9±3 years, 341 (64%) underwent AV replacement (54% isolated), and there were 104 (20%) deaths. On multivariable Cox proportional hazard survival analysis, a higher Society of Thoracic Surgeons score (hazard ratio, 1.21), lower % age-sex-predicted METs (hazard ratio 1.15), and slower heart rate recovery (hazard ratio, 1.22) were associated with higher longer-term mortality, whereas AV replacement (time-dependent covariate, hazard ratio, 0.26) was associated with improved survival. The addition of % age-sex-predicted METs to the Society of Thoracic Surgeons score resulted in significant reclassification of longer-term mortality risk (integrated discrimination index, 0.07 [0.03-0.11; P<0.001). In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction undergoing exercise stress echocardiography, a lower % of age-sex-predicted METs and slower heart rate recovery were associated with longer-term mortality, whereas AV replacement was associated with improved survival.

Abstract P041: Impaired Autonomic Control of Heart Rate at Rest and Slower Post-exercise Heart Rate Kinetics in Children with Congenital Heart Defects

Introduction: A slow recovery in heart rate (HR) following exercise is due to autonomic dysfunction and is associated with increased cardiovascular event risk. Children with congenital heart defects (CHD) display autonomic dysfunction as shown by a reduction in HR variability (HRV). Whether children with CHD have impairment in post-exercise HR recovery is unknown. Hypothesis: We tested the hypothesis that children with CHD would have reduced HRV at rest and slower HR recovery kinetics following 6-minute walk testing (6MWT) compared to healthy controls. Methods: Twenty-five children with CHD (11±2 years; males=14; females=11) and 21 age- and sex-matched controls (11±3 years; males=10; females=11) were studied. CHD diagnoses included Tetralogy of Fallot (n=7), pulmonary or aortic stenosis (n=3), hypoplastic left or right heart syndrome (n=5), Ebstien’s anomaly (n=1), atrial or ventricular septal defect (n=3), transposition of the great arteries (n=1), double inlet left ventricle (n=1), tricuspid atresia (n=1), coarctation of the aorta (n=2), single ventricle (n=1), and dilated cardiomyopathy (n=1). HRV was determined following 10 min supine rest using a 5 min surface ECG recorded epoch. Post-exercise HR kinetics were determined over a 4-min period following the 6MWT using telemetry-based HR. Mono-exponential modeling was used to derive a HR recovery time constant, tau (time to reach 63% change). Analyses were completed using unpaired t -tests with P &lt; 0.05 being significant. Data are mean ± SD. Results: Children with CHD had a lower 6MWT distance (513±75 vs. 599±81 m; P &lt; 0.001) and lower average exercise HR (122±15 vs. 139±18 beats/min; P = 0.001) compared to controls. Time domain HRV parameters revealed a reduction in the standard deviation of normal R-R intervals (55.9±40.4 vs. 92.1±24.5 ms), the root mean square of successive R-R interval differences (57.4±53.0 vs. 101.1±40.0 ms), and the percentage of consecutive normal R-R intervals that differ by more than 50 ms (24.6±28.7 vs. 53.2±14.0 %) in children with CHD vs. controls, respectively (all P &lt; 0.01). Power spectral HRV analyses revealed no difference in low frequency (LF) power (30±16 vs. 25±16 %; P &gt; 0.05), but significant differences in high frequency (HF) power (34±19 vs. 49±14 %) and the LF/HF ratio (1.4±1.5 vs. 0.6±0.3 %) in children with CHD vs. controls, respectively (all P &lt; 0.05). Post-exercise HR kinetics were slower in children with CHD (tau = 34±15 s) compared to controls (tau = 24±8 s; P = 0.01), indicating a longer recovery time for HR. Conclusions: Children with CHD have autonomic dysfunction as measured by a reduction in HRV and greater LF/HF ratio. Slower HR kinetics in children with CHD may be due to a reduction in parasympathetic activation during the post-exercise recovery period. Our findings suggest that autonomic dysfunction in children with CHD functionally alters HR control during or immediately following exercise.

Genetic variation in alpha2-adrenoreceptors and heart rate recovery after exercise.

Heart rate recovery (HRR) after exercise is an independent predictor of adverse cardiovascular outcomes. HRR is mediated by both parasympathetic reactivation and sympathetic withdrawal and is highly heritable. We examined whether common genetic variants in adrenergic and cholinergic receptors and transporters affect HRR. In our study 126 healthy subjects (66 Caucasians, 56 African Americans) performed an 8 min step-wise bicycle exercise test with continuous computerized ECG recordings. We fitted an exponential curve to the postexercise R-R intervals for each subject to calculate the recovery constant (kr) as primary outcome. Secondary outcome was the root mean square residuals averaged over 1 min (RMS1min), a marker of parasympathetic tone. We used multiple linear regressions to determine the effect of functional candidate genetic variants in autonomic pathways (6 ADRA2A, 1 ADRA2B, 4 ADRA2C, 2 ADRB1, 3 ADRB2, 2 NET, 2 CHT, and 1 GRK5) on the outcomes before and after adjustment for potential confounders. Recovery constant was lower (indicating slower HRR) in ADRA2B 301-303 deletion carriers (n = 54, P = 0.01), explaining 3.6% of the interindividual variability in HRR. ADRA2A Asn251Lys, ADRA2C rs13118771, and ADRB1 Ser49Gly genotypes were associated with RMS1min. Genetic variability in adrenergic receptors may be associated with HRR after exercise. However, most of the interindividual variability in HRR remained unexplained by the variants examined. Noncandidate gene-driven approaches to study genetic contributions to HRR in larger cohorts will be of interest.

Slow Heart Rate Recovery is Associated with Increased Exercise-induced Arterial Stiffness in Normotensive Patients

Slow Heart Rate Recovery is Associated with Increased Exercise-induced Arterial Stiffness in Normotensive Patients

Relation of heart rate recovery after exercise to insulin resistance and chronic inflammation in otherwise healthy adolescents and adults: results from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.

Insulin resistance (IR) and chronic inflammation are inversely related to heart rate recovery (HRR), a marker of cardiac autonomic function. Little is known, however, about the joint effects of IR and inflammation on HRR. The study sample consisted of 2649 healthy individuals aged 12-49 years with measures of submaximal cardiopulmonary fitness testing from the National Health and Nutrition Examination Survey 1999-2004. HRR 1-min (HRR1) and 2-min (HRR2) after recovery were recorded (bpm). IR was defined if homeostasis model assessment (HOMA-IR) was ≥ 2.73. C-reactive protein (CRP) was quantified by latex-enhanced nephelometry. In the fully adjusted model, participants with IR had attenuated HRR compared to those without (mean HRR1 11.8 vs. 12.7, p = 0.011; mean HRR2 31.2 vs. 33.4, p < 0.001). Mean HRR1 for participants with CRP >0.3 mg/dL, CRP 0.1-0.3 mg/dL, and CRP <0.1 mg/dL were 11.6, 12.0, and 12.8 (p for trend 0.002), respectively. Mean HRR2 in the three corresponding groups were 33.0, 32.5, and 31.8 (p for trend 0.033), respectively. Participants with IR and CRP elevation had slower HRR than those without IR and with normal CRP. The mean HRR1 comparing participants with IR/CRP >0.3 mg/dL to those with no IR/CRP <0.1 mg/dL were 10.5 and 13.1 (p < 0.001), while the mean HRR2 for the same comparison were 29.1 and 33.8 (p < 0.001). HRR (especially HRR2) was inversely correlated with various metabolic risks. Insulin resistance and CRP levels were inversely associated with HRR in healthy adolescents and adults. Participants with IR and elevated CRP had the worst HRR. Our findings suggest a joint effect of IR and inflammation on cardiac autonomic dysfunction.

Heart rate recovery after exercise and its relation with neutrophil-to-lymphocyte ratio in patients with cardiac syndrome X

The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are measures of systemic inflammation. Heart rate recovery (HRR) after exercise is influenced by autonomic function. The aim of this study was to ascertain whether HRR and the Duke Treadmill Score (DTS) values are related to NLR and PLR in patients with cardiac syndrome X (CSX). A total of 350 participants were enrolled in the study. Complete blood counts and high-sensitivity C-reactive protein (hsCRP) were obtained. All participants underwent an exercise test. HRR and DTS were calculated after exercise. Abnormal HRR was defined as 12 beats/min or less. CSX and coronary artery disease (CAD) groups had higher NLR, PLR, and hsCRP, and lower HRR and DTS values than the control group (for all, P<0.05). In both CSX and CAD groups, HRR was positively correlated with DTS (r=0.468, P<0.001 and r=0.491, P<0.001, respectively) and negatively correlated with NLR (r=-0.519, P<0.001 and r=-0.612, P<0.001, respectively), PLR (r=-0.422, P<0.001 and r=-0.438, P<0.001, respectively), and hsCRP (r=-0.553, P<0.001 and r=-0.521, P<0.001, respectively). NLR and hsCRP were important two predictors of the presence of lower HRR in both CSX [NLR: odds ratio (OR), 0.395; 95% confidence interval (CI), 0.168-0.925; P=0.032 and hsCRP: OR, 0.748; 95% CI, 0.591-0.945; P=0.015], and CAD groups (NLR: OR, 0.115; 95% CI, 0.026-0.501; P=0.004 and hsCRP: OR, 0.637; 95% CI, 0.455-0.892; P=0.009). CSX patients have higher NLR and PLR and slower HRR and lower DTS, similar to CAD patients, suggesting that CSX patients may be at a higher risk for developing cardiovascular events in the future. NLR may predict autonomic imbalance assessed by HRR in CSX.

High flow variant postural orthostatic tachycardia syndrome amplifies the cardiac output response to exercise in adolescents

Postural orthostatic tachycardia syndrome (POTS) is characterized by chronic fatigue and dizziness and affected individuals by definition have orthostatic intolerance and tachycardia. There is considerable overlap of symptoms in patients with POTS and chronic fatigue syndrome (CFS), prompting speculation that POTS is akin to a deconditioned state. We previously showed that adolescents with postural orthostatic tachycardia syndrome (POTS) have excessive heart rate (HR) during, and slower HR recovery after, exercise – hallmarks of deconditioning. We also noted exaggerated cardiac output during exercise which led us to hypothesize that tachycardia could be a manifestation of a high output state rather than a consequence of deconditioning. We audited records of adolescents presenting with long‐standing history of any mix of fatigue, dizziness, nausea, who underwent both head‐up tilt table test and maximal exercise testing with measurement of cardiac output at rest plus 2–3 levels of exercise, and determined the cardiac output () versus oxygen uptake () relationship. Subjects with chronic fatigue were diagnosed with POTS if their HR rose ≥40 beat·min−1 with head‐up tilt. Among 107 POTS patients the distribution of slopes for the , relationship was skewed toward higher slopes but showed two peaks with a split at ~7.0 L·min−1 per L·min−1, designated as normal (5.08 ± 1.17, N = 66) and hyperkinetic (8.99 ± 1.31, N = 41) subgroups. In contrast, cardiac output rose appropriately with in 141 patients with chronic fatigue but without POTS, exhibiting a normal distribution and an average slope of 6.10 ± 2.09 L·min−1 per L·min−1. Mean arterial blood pressure and pulse pressure from rest to exercise rose similarly in both groups. We conclude that 40% of POTS adolescents demonstrate a hyperkinetic circulation during exercise. We attribute this to failure of normal regional vasoconstriction during exercise, such that patients must increase flow through an inappropriately vasodilated systemic circulation to maintain perfusion pressure.

Tapering for Marathon and Cardiac Autonomic Function

The purpose of this study was to investigate changes in post-exercise heart rate recovery (HRR) and heart rate variability (HRV) during an overload-tapering paradigm in marathon runners and examine their relationship with running performance. 9 male runners followed a training program composed of 3 weeks of overload followed by 3 weeks of tapering (-33 ± 7%). Before and after overload and during tapering they performed an exhaustive running test (T(lim)). At the end of this test, HRR variables (e.g. HRR during the first 60 s; HRR(60 s)) and vagal-related HRV indices (e.g. RMSSD(5-10 min)) were examined. T(lim) did not change during the overload training phase (603 ± 105 vs. 614 ± 132 s; P = 0.992), but increased (727 ± 185 s; P = 0.035) during the second week of tapering. Compared with overload, RMSSD(5-10 min) (7.6 ± 3.3 vs. 8.6 ± 2.9 ms; P = 0.045) was reduced after the 2(nd) week of tapering. During tapering, the improvements in T(lim) were negatively correlated with the change in HRR(60 s) (r = -0.84; P = 0.005) but not RMSSD(5-10 min) (r = -0.21; P = 0.59). A slower HRR during marathon tapering may be indicative of improved performance. In contrast, the monitoring of changes in HRV as measured in the present study (i.e. after exercise on a single day), may have little or no additive value.