Marker Of Cardiac Autonomic Dysfunction Research Articles

Continuous Long-Term Assessment of Heart Rate Variability in Adults with Cyanotic Congenital Heart Disease after Surgical Repair.

Background: Heart rate variability (HRV) is an established, non-invasive parameter for the assessment of cardiac autonomic nervous activity and the health status in general cardiology. However, there are few studies on HRV in adults with congenital heart defects (CHDs). The aim of the present study was to evaluate the use of long-term continuous HRV measurement for the assessment of global health status in adults with cyanotic CHD. Methods: This prospective study included 45 adults (40% female, mean age = 35.2 ± 9.2 [range: 19-58] years) after cardiac surgical repair. HRV parameters were calculated from continuous 24 h measurements using a Bittium Faros 180 sensor (Bittium Corp., Oulu, Finland). Results: Postoperative patients with transposition of the great arteries (TGA) (n = 18) achieved significantly higher values of standard deviation of NN intervals (SDNN) (175.4 ± 59.9 ms vs. 133.5 ± 40.6 ms; p = 0.013) compared with patients with other conotruncal anomalies (n = 22). Comparing patients with TGA after a Senning-Brom or Mustard operation (n = 13) with all other heart surgery patients (n = 32), significantly higher HRV parameters were found after atrial switch (root mean square of successive RR interval differences: 53.6 ± 20.7 ms vs. 38.4 ± 18.3 ms; p = 0.019; SDNN: 183.5 ± 58.4 ms vs. 136.3 ± 45.3 ms; p = 0.006). A higher SDNN was also measured after Senning-Brom or Mustard operations than after a Rastelli operations (n = 2) (SDNN: 183.5 ± 58.4 ms vs. 84.5 ± 5.2 ms; p = 0.037). When comparing atrial switch operations (n = 3) with Rastelli operations, the SDNN value was significantly shorter in the Rastelli group (p = 0.004). Conclusions: Our results suggest that continuous HRV monitoring may serve as a marker of cardiac autonomic dysfunction in adults with cyanotic CHD after surgical repair. Impaired cardiac autonomic nervous activity may be associated with an increased risk of adverse reactions in patients with repaired CHD. Therefore, a longitudinal assessment of HRV patterns and trends may provide a deeper insight into dynamic changes in their autonomic regulation and disease progression, lifestyle changes, or treatments. As each person has individual variability in heart rate, HRV may be useful in assessing intra-individual disease progression and may help to improve personalized medicine. Further studies are needed to better understand the underlying mechanisms and to explore the full potential of HRV analysis to optimize medical care for ACHDs.

Cardiorespiratory coupling as an early marker of cardiac autonomic dysfunction in type 2 diabetes mellitus patients

The aim of this study was to assess cardiorespiratory coupling (CRC) in type 2 diabetes mellitus patients (T2DM) and apparently healthy individuals, in order to test the hypothesis that this method can provide additional knowledge to the information obtained through the heart rate variability (HRV). A cross-sectional study was conducted in T2DM patients(T2DMG=32) and health controls (CON=32). For CRC analysis, the electrocardiogram, arterial pressure, and thoracic respiratory movement were recorded at rest in supine position and during active standing. Beat-to-beat series of heart period and systolic arterial pressure were analyzed with the respiratory movement signal via a traditional non-causal approach, such as squared coherence function. In this sample of T2DM, no differences in HRV were observed when compared to the CON, but the T2DMG showed a reduction in resting CRC. We conclude that in CRC in T2DM, reflected by the squared coherence may already be compromised even before HRV changes.

Factors Associated with Heart Rate Recovery in People with Chronic Obstructive Pulmonary Disease: An Analytical Cross-Sectional Study

Introduction: Heart rate recovery (HRR) delay is a marker of cardiac autonomic dysfunction. In people with chronic obstructive pulmonary disease (COPD) attending pulmonary rehabilitation programs, assessing HRR could have prognostic utility, yielding valuable information for setting treatment goals and targets in therapeutic interventions. Therefore, this study aimed to establish the sociodemographic, pulmonary function, and functional aerobic capacity differences in people with COPD with normal and abnormal HRR during the 6-minute walk test (6MWT) and explore factors associated with abnormal HRR. Method: Analytical cross-sectional study. Sociodemographic, anthropometric characteristics, pulmonary function, aerobic capacity, BODE index, and Hospital Anxiety and Depression Scale (HADS) were assessed in COPD patients. An HRR cut-off point of 14 beats or more was used to define HRR delay. Results: Of 128 patients included, 89 (69.5%) showed abnormal HRR. Patients with abnormal HRR were classified with higher overweight/obesity, lower resting SpO2 and lower distance walked, predicted percentage, and estimated VO2 in the 6MWT, with more significant symptoms at one minute after the end of the test (dyspnea and fatigue). In the multivariate regression model adjusted for age, sex, resting heart rate, and FEV1, findings showed that distance walked in the 6MWT (OR 0.994, p-value=0.010), fatigue at 1 minute (OR 2.12, p-value=0.000), and HADS depression domain (OR 0.87, p-value=0.018) are factors associated with HRR. Conclution: In outpatients with COPD, HRR relates to the distance walked in the 6MWT, fatigue, and depression measured with the HADS.

Short-term deceleration capacity of heart rate: a sensitive marker of cardiac autonomic dysfunction in idiopathic Parkinson’s disease

Cardiac autonomic dysfunction in idiopathic Parkinson's disease (PD) manifests as reduced heart rate variability (HRV). In the present study, we explored the deceleration capacity of heart rate (DC) in patients with idiopathic PD, an advanced HRV marker that has proven clinical utility. Standard and advanced HRV measures derived from 7-min electrocardiograms in 20 idiopathic PD patients and 27 healthy controls were analyzed. HRV measures were compared using regression analysis, controlling for age, sex, and mean heart rate. Significantly reduced HRV was found only in the subcohort of PD patients older than 60years. Low- frequency power and global HRV measures were lower in patients than in controls, but standard beat-to-beat HRV markers (i.e., rMSSD and high-frequency power) were not significantly different between groups. DC was significantly reduced in the subcohort of PD patients older than 60years compared to controls. Deceleration-related oscillations of HRV were significantly reduced in the older PD patients compared to healthy controls, suggesting that short-term DC may be a sensitive marker of cardiac autonomic dysfunction in PD. DC may be complementary to traditional markers of short-term HRV for the evaluation of autonomic modulation in PD. Further study to examine the association between DC and cardiac adverse events in PD is needed to clarify the clinical relevance of DC in this population.

Prognostic value of reduced heart rate reserve during exercise stress-echocardiography in hypertrophic cardiomyopathy

Abstract Background Heart rate reserve (HRR) during exercise evaluates chronotropic incompetence and is a prognostically important marker of cardiac autonomic dysfunction, additive to regional wall motion abnormalities (RWMA) in patients with coronary artery disease. Objectives To assess determinants and prognostic value of HRR in patients with hypertrophic cardiomyopathy (HCM). Methods From 1998 to 2019, we enrolled 774 HCM patients (age = 48.8±15.9 years, 410 men) with exercise stress echocardiography (ESE) in 10 certified centres of the international stress echo network. During ESE we assessed: left ventricular outflow tract obstruction (LVOTO, significant when >50 mmHg); RWMA; HRR (peak/ rest heart rate), 344 in beta-blockers therapy (44.4%). Patients were followed for a median 49 months (IQ range, 25–78 months). The study end-point was all-cause mortality. Results During ESE, we observed stress-induced RWMA in 42 (5.4%) and LVOTO in 248 (33%); HRR was 1.92.±0.41. There were no difference in patients with normal and abnormal HRR with and without beta-blockers therapy (147, 41.1% vs 211, 58.9%, p=0.079). During follow-up, 43 deaths occurred. Beta blockers therapy in univariate analysis did not have prognostic role (HR 1.105, 95% CI 0.602–2.028, p=0.768). The lowest HRR quartile (≤1.62) had a 10-fold higher 6-year death rate (10.9%) than the highest quartile (>2.16, 1.04%): see figure. At multivariable analysis, lowest HRR quartile (HR 2.074, 95% CI 1.082–6.773, p=0.034), age (HR 1.045, 95% CI 1.014–1.077, p=0.004), maximal wall thickness (HR 1.137, 95% CI 1.054–1.226, p=0.001), stress-induced RWMA s(HR 4.289, 95% CI 1.733–10.615, p=0.002) and ≥ moderate mitral regurgitation at rest (HR 3.127, 95% CI 1.507–6.488, p=0.002) predicted death. Conclusions A blunted HRR during ESE predicts adverse outcome independent of inducible RWMA in HCM patients. Autonomic dysfunction deserves consideration as a potential therapeutic target in this disease. Figure 1 Funding Acknowledgement Type of funding source: None

Exposure to acrylamide and reduced heart rate variability: The mediating role of transforming growth factor-β

The potential adverse health effects of acrylamide have drawn worldwide attention and the World Health Organization has urged further urgent studies on its health threat. Herein we explored the exposure-response relationship and underlying mechanism between internal acrylamide exposure and heart rate variability (HRV) alteration, a marker of cardiac autonomic dysfunction. We measured six HRV indices and two urinary acrylamide metabolites (N-Acetyl-S-(2-carbamoylethyl)-l-cysteine, AAMA; N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine, GAMA) for 2997 general Chinese adults from the Wuhan-Zhuhai cohort, of whom 2414 had data on plasma transforming growth factor-β1 (TGF-β1). The associations among urinary acrylamide metabolites, HRV and TGF-β1 were evaluated by linear mixed models and restricted cubic spline models. The mediating role of TGF-β1 was investigated by conducting mediation analysis. We found significantly negative dose-response relationships of all urinary acrylamide metabolites and TGF-β1 with all six HRV indices after adjusting for potential confounders (all P < 0.05). Urinary GAMA (β=0.074, P < 0.05) rather than AAMA (β=0.024, P > 0.05) was positively and dose-dependently associated with TGF-β1, which in turn significantly mediated 5.71–7.41 % of the GAMA-associated HRV reduction. Our findings suggest for the first time that daily exposure of general population to acrylamide is associated with cardiac autonomic dysfunction, where a mechanism involving TGF-β pathway may be involved.

P330 Blunted heart rate reserve during vasodilator stress echocardiography in diabetic and renal failure patients

Abstract Funding Acknowledgements None Background A blunted heart rate reserve (HRR) during dipyridamole stress echo (SE) is a marker of cardiac autonomic dysfunction associated with poor outcome, independently of inducible ischemia, underlying coronary artery disease (CAD) and beta-blocker therapy. Patients with diabetes and/or renal failure have higher prevalence of underlying autonomic dysfunction. Aim. To assess the value of HRR in patients undergoing dipyridamole SE. Methods We prospectively recruited a sample of 61 patients with known or suspected CAD (mean age 75 ± 10 years; 34 males, 55,7%; 50% on beta-blockers at the time of testing). Coexistent atrial fibrillation or previous pacemaker implantation were considered as exclusion criteria. Three groups were identified a priori: non-diabetic with normal renal function (n = 43, Group 1); diabetics, with normal renal function (n = 14, Group 2); severely impaired renal function on dialysis (n = 4, Group 3). All patients underwent dipyridamole SE (0.84 mg/kg in 10"). Wall motion score Index (WMSI) was calculated with a 17-segment score of left ventricle, each segment scored from 1= normal to 4= dyskinetic. HRR was measured by ECG as the peak/rest HR ratio. Results A positive SE (stress WMSI&amp;gt; rest WMSI) was present in 2 patients of Group 1 (4.7%), 4 of Group 2 (28.6%) and no patient in Group 3. Heart rate was different, although not significant, among the 3 groups both at rest (66.1 ± 11.1 vs 64.6 ± 8.5 vs 79.0 ± 8.0, p = 0.050) and at peak stress (83.8 ± 12.6 vs 75.3 ± 10.3 vs 86.5 ± 11.1, p = 0.059). Of note, HRR was statistically different among groups (1.29 ± 0.20 vs 1.19 ± 0.14 vs 1.09 ± 0.06, p &amp;lt; 0.047; see figure). There was no difference in HRR between patients off and on-beta-blockers (1.19 ± 0.16 vs 1.24 ± 0.24, p = 0.421) and with or without positive SE (1.20 ± 0.14 vs 1.25 ± 0.20, p = 0.530). Overall, HRR ≤ 1.17 (median value) was reported in 39.5% of Group 1, 71.4% of Group 2, and 100% of Group 3 pts (p = 0.024). No significant correlations between HRR and peak WMSI (p = 0.183) or age (0.062) were reported. Conclusion HRR is frequently abnormal in patients referred for SE testing, especially in presence of concomitant diabetes and advanced renal failure. The blunted chronotropic response is a simple, imaging independent marker of cardiac autonomic dysfunction and may usefully complement the conventional evaluation with regional wall motion abnormalities during vasodilator SE. Abstract P330 Figure title: HRR box plots

Abstract 14: Is Low Heart Rate Variability, a Marker of Autonomic Dysfunction, the Missing Link Between Migraine With Visual Aura and Cardioembolic Stroke?

Introduction: Migraine with visual aura (MA) has been associated with the risk of cardioembolic stroke (CES). Low heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been shown to be associated with atrial fibrillation (AF) and risk of stroke. We investigated the association between low HRV and MA. We also examined whether the MA associated CES risk can be explained by a low HRV. Methods: Participants in the Atherosclerosis Risk in Communities cohort were interviewed for migraine history in 1993-1995; during a subsequent follow-up visit (1996-1998) HRV was measured using 6-minute EKG. HRV indices were calculated using the standard deviation of RR intervals (SDNN), the mean of all normal RR intervals (MeanNN), the root mean square of successive differences of RR intervals (RMSSD), low (LF) and high (HF) frequency power, and the LF/HF ratio. All HRV measures were categorized into quintiles. Logistic regression models were used to estimate ORs adjusted for sociodemographic and comorbid confounders. Mediation analysis was conducted to test if HRV was a mediator of MA associated CES risk, using Barron-Kenny’s causal step tests. Results: Of 11,939 participants assessed for headache 426 reported MA. A total of 164 incident CES occurred over a 20-year follow-up period. After covariate adjustment, there was a strong evidence of an association between low HRV and MA. The lowest HRV quintile was associated with higher odds of MA compared with the highest quintile for SDNN (OR, 1.5, 95% CI, 1.1–2.3), RMSSD (OR, 1.4; 95% CI, 1.1–2.1), LF (OR, 1.3; 95% CI, 1.0–1.8), HF (OR, 1.5; 95% CI, 1.1–2.1), and LF/HF ratio (OR, 1.5; 95% CI, 1.1–2.0). The data also suggests HRV may be a potential mediator between MA and CES. Conclusion: MA was associated with low HRV, suggestive of chronic autonomic dysfunction among this population. Alongside prior findings showing HRV-AF, HRV-Stroke and AF-Stroke link, the association may provide the missing link between MA and Stroke (Figure).

Heart rate recovery is associated with ventilatory constraints and excess ventilation during exercise in patients with chronic obstructive pulmonary disease.

Background Heart rate recovery delay is a marker of cardiac autonomic dysfunction. In chronic obstructive pulmonary disease patients, the ventilatory response to exercise during incremental cardiopulmonary exercise test may add information about dynamic hyperinflation by low values of inspiratory capacity/total lung capacity ratio (at peak) and excess ventilation by the slope of minute ventilation to carbon dioxide output ratio (VE/VCO2 slope). We aimed to assess if the ventilatory response to exercise might be a determinant for heart rate recovery delay. Design An observational, prospective study. Methods Anthropometric characteristics, lung function and cardiopulmonary exercise test data were recorded in chronic obstructive pulmonary disease outpatients. A cut-off of heart rate recovery of 12 or more beats was used to define heart rate recovery delay. Results Of 254 patients enrolled, 156 (61%) showed heart rate recovery delay. As compared to patients with normal heart rate recovery, patients with delay were older, with a worse lung function and with lower values of peak oxygen uptake, maximal workload, oxygen pulse at rest and at peak, and inspiratory capacity/total lung capacity at peak. Conversely, VE/VCO2 slope and dyspnoea and leg fatigue perception at peak were higher in patients with heart rate recovery delay. In the multivariate regression model adjusted for age, sex, fat-free mass, heart rate at rest and use of β-blockers, we found that inspiratory capacity/total lung capacity at peak (<0.25) (odds ratio 2.61; P = 0.007) and VE/VCO2 slope (>32) (odds ratio 2.26; P = 0.018) predict the risk of heart rate recovery delay. Conclusions In chronic obstructive pulmonary disease outpatients, heart rate recovery is associated with dynamic hyperinflation and excess ventilation during exercise.

Evidence of reduced parasympathetic autonomic regulation in inflammatory joint disease: A meta-analyses study.

Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are inflammatory joint disorders (IJD) with increased risk of cardiovascular disease (CVD). Autonomic dysfunction (AD) is a risk factor for CVD, and parasympathetic AD is linked to key features of IJD such as inflammation, physical inactivity and pain. Heart-rate variability (HRV) is a marker of cardiac AD. The study objective was to compare parasympathetic cardiac AD, measured by HRV, between patients with IJD and healthy controls, using meta-analysis methodology, and to examine the impact of inflammation, physical inactivity and pain on HRV in IJD. Medline, Embase and Amed were searched. Inclusion criteria were adult case-control studies published in English or a Scandinavian language, presenting HRV data in IJD. Two measures of HRV and 3 from the Ewing protocol were selected: square root of mean squared difference of successive R-R intervals (RMSSD), high frequency (HF), Ewing protocol; standing (E-S), breathing (E-B) and Valsalva (E-V). Patients with RA, SpA and healthy controls were compared separately using random-effects meta-analyses of standardized mean differences (SMD). In all, 35 papers were eligible for inclusion. For RMSSD the pooled SMD (95% CI) RA vs. controls was -0.90 (-1.35 to -0.44), for SpA vs. controls; -0.34 (-0.73 to 0.06). For HF pooled SMD RA vs. controls was -0.78 (-0.99 to -0.57), for SpA vs. controls; -0.04 (-0.22 to 0.13). All Ewing parameters were significantly lower in cases, except for E-V which was comparable between cases and controls in patients with RA. Patients with IJD have cardiac parasympathetic AD which is related to inflammation.

Heart Rate Variability and Cognitive Function In Middle-Age Adults: The Coronary Artery Risk Development in Young Adults.

Low heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been associated with major risk factors of cognitive impairment. Yet, the direct association of HRV with cognitive function remains relatively unexplored, particularly in midlife. In 2005, 2 measures of short-term HRV, the SD of normal-to-normal intervals (SDNN) and the root mean square of successive differences (RMSSD), were calculated for participants of the Coronary Artery Risk Development in Young Adults study, and then categorized into quartiles. Five years later, 3 cognitive tests were administered for verbal memory ("Rey Auditory-Verbal Learning Test", RAVLT, range 0-15), processing speed ("Digit Symbol Substitution Test", DSST, range 0-133), and executive function ("Stroop interference"). Two thousand one hundred and eighteen participants (57.7% female, 42.2% Black) with a mean baseline age of 45.3 years were included in this analysis. In demographic-adjusted models, compared to participants with quartile 1 SDNN (lowest quartile), participants in the upper quartiles of SDNN scored better on the DSST (quartile 4: β = 1.83 points better, P = 0.03; and quartile 3: β = 1.95 points better, P = 0.03) and on the stroop (quartile 3: β = 1.19 points better, P < 0.05; and quartile2: β = 1.44 points better, P = 0.02). After adjusting for behavioral and cardiovascular risk factors, higher quartile SDNN remained significantly associated with better stroop score (quartile 3: β = 1.21 points better, P = 0.04; and quartile 2: β = 1.72 points better, P < 0.01) but not with DSST. There was no association between quartile of RMSSD and cognitive function, from fully adjusted models. Our findings suggest that higher quartile SDDN is associated with better executive function in midlife, above, and beyond cardiovascular risk factors.

HEART RATE VARIABILITY AND COGNITIVE FUNCTION IN MIDDLE-AGE ADULTS: THE CARDIA STUDY

Lower heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been associated with major risk factors of cognitive impairment. Yet the direct association of HRV with cognitive function remains relatively unexplored, particularly early in the life course. We used data from the Coronary Artery Risk Development in Young Adults to examine whether measures of HRV are associated with cognitive function in middle-age. In 2005 (our study baseline), two measures of HRV, standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences (RMSSD), were calculated using 10-second 12-lead electrocardiogram. Lower SDNN (2.6ms to 17.4ms) and lower RMSSD (2.2ms to 17.8ms) were defined as the lowest quartiles. Five years later, in 2010, three cognitive tests were administered including a test of verbal memory (Rey Auditory-Verbal Learning Test, RAVLT, range 0–15), processing speed (Digit Symbol Substitution Test, DSST, range 0–133), and executive function (Stroop interference). 2,118 participants (57.7% female, 42.2% black) with a mean baseline age of 45.3 years were included in this analysis. In demographic-adjusted models, compared to participants with the upper three quarters of SDNN, participants with lower SDNN scored 1.76 points worse on DSST (p=0.01) and 1.14 points worse on Stroop (p=0.02). After adjusting for behavioral and cardiovascular risk factors, lower SDNN remained significantly associated with worse stroop (p=0.01) but not with DSST. There was no association between RMSSD and cognitive function. Our findings suggest that lower SDDN is associated with worse executive function among middle-aged adults, above and beyond cardiovascular risk factors.

Heart Rate Variability and Incident Stroke

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

RELATION OF HEART RATE RECOVERY AFTER EXERCISE TO INSULIN RESISTANCE AND CHRONIC INFLAMMATION IN HEALTHY ADOLESCENTS AND YOUNG ADULTS: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES) 1999-2004

Impaired heart rate recovery (HRR) after exercise, a marker of cardiac autonomic dysfunction, predicts mortality in healthy adults. Although there is an inverse relation of both inflammation (IF) and insulin resistance (IR) to HRR, little is known about the combined effect of IR and IF on HRR. The

Post-exercise heart rate recovery and mortality in chronic obstructive pulmonary disease

Abnormal heart rate recovery (HRR) after exercise, a marker of cardiac autonomic dysfunction, is associated with poor prognosis in various populations. As chronic obstructive pulmonary disease (COPD) is associated with cardiac autonomic dysfunction, we tested the hypothesis that patients with COPD have a lower HRR than healthy people, and evaluated whether a delay in HRR is associated with an increased risk of mortality in COPD. The records of 147 COPD patients were reviewed (65.1+/-9.1 years, mean+/-sd, 42 women/105 men, forced expiratory volume in 1s (FEV1): 42+/-15% predicted) and compared to 25 healthy subjects (61.6+/-4.5 years, 5 women/20 men, FEV1: 100+/-14% predicted) during recovery after an exercise test. Heart rate was measured at peak exercise and at 1-min recovery, the difference between the two being defined as HRR (11+/-9 beats in COPD patients vs. 20+/-9 beats in healthy subjects, P < 0.0001). During a mean follow-up of 43.1+/-22.0 months, 32 patients died. Abnormal HRR (14 beats) was a strong predictor of mortality in COPD patients (adjusted hazard ratio: 5.12, 95% CI [1.54-17.00]). In conclusion, COPD patients have a lower HRR than healthy subjects, and have a worse prognosis when presenting abnormal HRR.