Heart Rate Variability Reflects Severity of COPD in PiZ α1-Antitrypsin Deficiency

doi:10.1378/chest.113.2.327

Chest

Volume 113, Issue 2, February 1998, Pages 327-333

https://doi.org/10.1378/chest.113.2.327 Get rights and content

Background

Analysis of heart rate variability (HRV) is a powerful method of assessing severity of conditions affecting the autonomic nervous system.

Study objective

To determine if HRV is decreased and if HRV reflects severity in COPD.

Design

Prospective determination of HRV from 24-h outpatient Holter recordings.

Patients

Eighteen individuals with PiZ α₁-antitrypsin deficiency: 13 with COPD and 5 with normal FEV₁. HRV was also determined in 18 matched normal control subjects. Approximately 3 years after the initial recording, all COPD subjects were contacted to determine current status.

Measurements

Indexes of heart rate (HR) and HRV were compared for groups of patients with and without COPD and their control subjects.

Results

Mean and minimum HRs were higher in COPD patients. Virtually all indexes of HRV were significantly decreased in COPD patients. No differences were found in HR or HRV between PiZ individuals with normal FEV₁ and their age-and gender-matched control subjects. Patients who had a change in status (ie, death, lung transplant, listed for transplant) had significantly higher daytime HRs, lower values for HRV indexes reflecting mixed sympathetic and parasympathetic modulation of HR, and reduced daytime high-frequency spectral power, an index of cardiac vagal modulation. Significant correlations (r=0.48 to 0.88) were found between FEV₁ and these and other indexes of HRV. Most other indexes of HRV also tended to be lower for the group whose status had changed.

Conclusion

PiZ α₁-antitrypsin deficiency COPD is associated with abnormal cardiac autonomic modulation. Indexes of HRV appear to reflect severity and may have prognostic value in COPD patients.

Section snippets

Subjects

Eighteen individuals, 5 female, 13 male, aged younger than 47 years, with marked α₁-antitrypsin deficiency documented by serum concentrations and phenotype PiZ (Central Phenotyping Lab; National Institute of Child Health and Human Development; Bethesda, Md; or Alpha-1 Antitrypsin Deficiency Detection Program; Salt Lake City) gave informed consent for this study, which was approved by the Institutional Review Board of Jewish Hospital. Thirteen of the 18 PiZ subjects had COPD (FEV₁, 15 to 49%)

HR, HRV, and Ectopy Did Not Differ Between PiZ Individuals With Normal FEV₁ and Control Subjects

When PiZ individuals with normal FEV₁ (n=5) were compared with their age- and gender-matched control subjects (n=5), mean values were similar and no significant differences were found in ectopy or in any index of HR or HRV. The number of patients was small, so that we lacked the statistical power to detect a difference in HRV of <20%. The remainder of the comparisons were made between PiZ COPD patients and their age- and gender-matched control subjects.

HR Is Increased in PiZ COPD Patients

Table 1 shows age, ectopy, and HR

Multiple Measures of HRV

We have presented a large number of HRV indexes, many of which are highly correlated and can, under some circumstances, be used as surrogates for each other.¹⁶ These measures constitute those that are commonly reported in the clinical literature. To understand their clinical significance, it is most useful to think of them, as presented in the results and tables, as reflecting purely vagal influences, reflecting a mixture of sympathetic and parasympathetic modulation of HR and reflecting

ACKNOWLEDGMENTS

The authors thank Pamela Wilson for secretarial assistance.

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Cited by (76)

Dynamic hyperinflation, chronotropic intolerance and abnormal heart rate recovery in non-severe chronic obstructive pulmonary disease patients-reflections in the mirror
2022, Pulmonology
The presence of abnormal heart rate recovery (HRR) and chronotropic incompetence (CI) suggests autonomic dysfunction (AD) and is associated with diminished physical activity and increased cardio-vascular (CV) risk.
Our aim is to analyse the correlation between AD and airflow obstruction - forced expiratory volume in 1 s (FEV1), dynamic hyperinflation (DH) and disease prognosis - the BODE ... index (BMI; Obstruction ... FEV1;Dyspnea ... mMRC;E ... exercise capacity) in non-severe COPD patients without overt CV comorbidities.
We used cardio-pulmonary exercise testing (CPET) with 67 subjects. Inspiratory capacity (IC) manouevres were performed for DH assessment. Echocardiography was executed before CPET and 1...2 min after peak exercise. Stress left ventricular diastolic dysfunction (LVDD) was assumed if stress E/e... > 15.Wilkoff method calculated the metabolic-chronotropic relationship (MCR). Chronotropic incompetence (CI) and abnormal HR recovery (HRR) were determined.
CI was detected in 44% of the mild and 65% of the moderate COPD patients. Abnormal HRR was present in 75% of the mild and 78% of the moderate COPD subjects. Multivariate regression analysis showed no association between FEV1, CPET parameters, BODE index, stress LVDD and AD. DH was the only independent predictor for both abnormal HRR and CI.
Evaluation of AD during incremental CPET unravels lung hyperinflation as a potential mechanism of attenuated HR response and diminished physical activity in non-severe COPD free of overt CV comorbidities. This multifaceted approach to dyspnea may facilitate the discrimination of its pathogenesis and improve its proper clinical management.
The exclusive presence of the chronic pulmonary disease could be more important in affecting autonomic cardiac modulation than the severity of airflow obstruction: Analysis using heart rate variability
2018, Biomedical Signal Processing and Control
Citation Excerpt :
Also, the effect size of the results using different statistical analysis, considering confounding factors such as sex, age and BMI, were included in the present study. In the classic study of Stein et al. [3], HRV seemed to have an important prognostic value in the severity of COPD since the authors found significant associations between different indices of HRV and FEV1 in the night and day periods; however, despite presenting significant correlations between various indices of HRV the individuals were younger and the authors did not present results on the severity classification distribution or body mass information. In the present study, individuals with both high airflow and low airflow obstruction of COPD presented lower HRV than the control group, but there were no significant differences related to the degree of severity observed through indices of heart rate variability, independent of the age, sex and BMI.
The autonomic nervous system regulates the caliber of the airways, blood flow, secretion production, modulates the inflammatory response and modulates airway responses to inflammation. Despite this, some intrinsic features could be more important in affecting autonomic modulation than the airflow severity. This study aimed to analyze the effects of chronic obstructive pulmonary disease (COPD) on autonomic modulation through heart rate variability (HRV) and its relationship with airflow severity. Outpatients with COPD (n = 30) and a control group (n = 26) were evaluated. The main outcome measures were anthropometry, spirometry and HRV. The presence of COPD had a large effect on autonomic modulation, demonstrated by a significant reduction in 6 out of 12 HRV indices according to the comparisons between the COPD groups (high and low severity) and the control group through HRV indices (rMSSD: 13.5 ± 7.3 vs. 10.4 ± 6.3 vs. 20.7 ± 7.1 ms; SDNN: 22.0 ± 11.2 vs. 17.1 ± 8.0 vs. 33.6 ± 13.8 ms; SD1: 9.6 ± 5.2 vs. 7.4 ± 4.5 vs. 14.6 ± 5.0 ms; SD2: 29.5 ± 15.2 vs. 22.9 ± 10.7 vs. 44.8 ± 20.0 ms). However, the severity of COPD presented no significant differences even when considering age, sex and body mass index (BMI). This study suggests that the presence of COPD could be more important in affecting HRV than the severity of airflow obstruction, independent of the sex, age or BMI.
Changes of heart rate variability predicting patients with acute exacerbation of chronic obstructive pulmonary disease requiring hospitalization after Emergency Department treatment
2018, Journal of the Chinese Medical Association
Citation Excerpt :
In a previously conducted study, the increase in total power, low frequency (LF) component, and low LF/high frequency (HF) ratio (LF/HF ratio) pointed to the fact that intermittent hypoxic training increased the response of the autonomic nervous system, predominantly through increased sympathetic activity.8 The indexes of HRV appear to reflect severity and may have prognostic value in COPD patients.9 Patients with AECOPD have increased HRV parameters than those with stable COPD.10
Indexes of heart rate variability (HRV) appear to reflect severity and may have prognostic value in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We hypothesized that AECOPD without adequate treatment response would demonstrate impaired cardiac autonomic regulation and changes in HRV after emergency department (ED) treatment.
A prospective study of measuring HRV in admitted and discharged patients with AECOPD shortly after ED arrival and again 24 h after treatment.
Total consecutive 33 patients (18 admitted and 15 discharged, age 77.1 ± 1.6 years) were enrolled. Among admitted patients, high frequency in normalized unit (HF%) was significantly lower (P < 0.001) while Ratio of LF to HF (LF/HF ratio) was significantly higher (P < 0.001) than discharged. 24 h after treatment, admitted patients had a significantly larger increase in HF% (P < 0.002) and larger decrease in LF/HF ratio (P < 0.05) than discharged. ROC curve analysis show the relative potential of the ΔHF% and ΔLF/HF% in the discrimination of groups. The area under the ROC curve between the 2 groups was 0.807 (P < 0.01) and 0.722 (P < 0.05), respectively. The best cut-off value for the admission between groups was ΔHF% >7.1 and ΔLF/HF% ≦−0.39.
Patients with AECOPD requiring admission after ED treatment had a greater increase in HF% and greater decrease in LF/HF ratio compared to those discharged. Our study demonstrates patient with ΔHF% was >7.1 or a ΔLF/HF% ≦−0.39 require admission despite 24 h of ED treatment.
Inspiratory loading and limb blood flow in COPD: The modulating effects of resting lung hyperinflation
2016, Respiratory Physiology and Neurobiology
Inspiratory resistive loading (IRL) may have deleterious cardiocirculatory effects leading to poor peripheral perfusion in severely-hyperinflated patients with COPD. Nineteen patients (13 severely-hyperinflated with inspiratory capacity/total lung capacity ratio ≤ 0.28) underwent calf blood flow (CBF) measurements by venous occlusion plethysmography at rest and during IRL at 60% maximal inspiratory pressure. Severely-hyperinflated patients had lower resting CBF and greater calf vascular resistance (CVR) than moderately-hyperinflated patients (p < 0.05). All severely-hyperinflated patients had markedly reduced CBF (p = 0.01). Opposite to our main hypothesis, however, IRL did not further reduce CBF in these patients (p > 0.05). Conversely, it significantly decreased CBF and increased CVR in moderately-hyperinflated patients; in fact, end-trial CBF and CVR did not differ between the groups (p > 0.05). In conclusion, marked impairments in resting appendicular blood flow in severely-hyperinflated patients with COPD were seen only after acute IRL in less hyperinflated patients. These findings set the stage for studies investigating the effects of lung deflation on peripheral hemodynamics in patients with severe hyperinflation.
Effect of lung transplantation on heart rate response to exercise
2015, Heart and Lung: Journal of Acute and Critical Care
Citation Excerpt :
A chronic increase in resting heart rate (HR) has been associated with poor prognosis in various cardiovascular diseases and is associated with altered autonomic function and risk of sudden death.1,2 Abnormalities in autonomic control and elevated resting heart rates are known to be present in patients with chronic obstructive pulmonary disease (COPD)3–6 and respiratory failure.6–8 An example of this is seen with reduced parasympathetic activity (determined from decreased heart rate variability parameters) that has been thought to be a potential cause of an elevated resting HR in lung transplant recipients.2,9
To evaluate if patients have a change in percent of predicted heart rate reserve used at peak exercise (%HRR) after lung transplantation, even at matching workloads.
Lung disease of obstructive, restrictive, and mixed types may be associated with an autonomic imbalance. Lung transplantation may improve the effects of pulmonary disease on cardiac function. However, the effect of lung transplantation on heart rate responses during exercise has not been investigated in detail.
Retrospective review of patients who underwent lung transplantation. Pre and post transplant cardiopulmonary exercise tests were reviewed.
The %HRR significantly improved by a median of 37% (p < 0.001) following lung transplantation. When matching workloads were analyzed, the %HRR also decreased from a median of 36% to 24% (p < 0.001).
Corresponding to an increase in peak exercise capacity, percentage of heart rate reserve used improves significantly after lung transplantation, even at matching workloads, indicating a likely improvement in autonomic modulation.
The effect of anxiety on heart rate variability, depression, and sleep in Chronic Obstructive Pulmonary Disease
2013, Journal of Psychosomatic Research
The current study investigates heart rate variability (HRV) responses to a psychosocial stressor in Chronic Obstructive Pulmonary Disease (COPD) patients, and the potential role of anxiety as a confounding factor in this relationship. Additionally, this study also investigates the influence of anxiety on sleep and depressive symptoms among COPD patients.
The study utilized a 2 (disease status) × 2 (anxiety group) factorial design examining HRV associated with anxiety symptoms and COPD during a standardized acute social stress task. Participants (mean age 59.1 ± 11.2 years; 50% female) completed pulmonary function testing, HRV monitoring, and self-report questionnaires assessing psychological factors. 30 COPD patients were age- and gender-matched with 30 healthy controls.
HRV response to a psychosocial stressor among participants with higher anxiety (both COPD and healthy) reflected autonomic dysregulation in both time and frequency domains that was not evident among non-anxious participants. COPD participants with higher anxiety reported greater symptoms of depression and poorer sleep quality than did COPD participants with low anxiety.
Anxiety is associated with dysregulated HRV response to a psychosocial stressor, but the negative influence of anxiety and COPD on autonomic function did not appear to be additive. Comorbid anxiety in patients with COPD is associated with increased behavioral and psychological symptoms of distress.

View all citing articles on Scopus

: revision accepted July 28.

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Chest

Clinical Investigations: COPDHeart Rate Variability Reflects Severity of COPD in PiZ α1-Antitrypsin Deficiency

Background

Study objective

Design

Patients

Measurements

Results

Conclusion

Section snippets

Subjects

HR, HRV, and Ectopy Did Not Differ Between PiZ Individuals With Normal FEV1 and Control Subjects

HR Is Increased in PiZ COPD Patients

Multiple Measures of HRV

ACKNOWLEDGMENTS

Chest

Chest

Chest

Am J Cardiol

Cardiol Clin

Am J Cardiol

Am J Cardiol

Am J Cardiol

J Electrocardiol

Respir Med

Prognosis in chronic obstructive pulmonary disease

Am Rev Respir Dis

Clinical Investigations: COPD
Heart Rate Variability Reflects Severity of COPD in PiZ α₁-Antitrypsin Deficiency

HR, HRV, and Ectopy Did Not Differ Between PiZ Individuals With Normal FEV₁ and Control Subjects