Brief Rapid Communications
Slow Breathing Increases Arterial Baroreflex Sensitivity in
Patients With Chronic Heart Failure
Luciano Bernardi, MD; Cesare Porta, MD; Lucia Spicuzza, MD; Jerzy Bellwon, MD;
Giammario Spadacini, MD; Axel W. Frey, MD; Leata Y.C. Yeung, MD; John E. Sanderson, MD;
Roberto Pedretti, MD; Roberto Tramarin, MD
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Background—It is well established that a depressed baroreflex sensitivity may adversely influence the prognosis in
patients with chronic heart failure (CHF) and in those with previous myocardial infarction.
Methods and Results—We tested whether a slow breathing rate (6 breaths/min) could modify the baroreflex sensitivity in
81 patients with stable (2 weeks) CHF (age, 58⫾1 years; NYHA classes I [6 patients], II [33], III [27], and IV [15])
and in 21 controls. Slow breathing induced highly significant increases in baroreflex sensitivity, both in controls (from
9.4⫾0.7 to 13.8⫾1.0 ms/mm Hg, P⬍0.0025) and in CHF patients (from 5.0⫾0.3 to 6.1⫾0.5 ms/mm Hg, P⬍0.0025),
which correlated with the value obtained during spontaneous breathing (r⫽⫹0.202, P⫽0.047). In addition, systolic and
diastolic blood pressure decreased in CHF patients (systolic, from 117⫾3 to 110⫾4 mm Hg, P⫽0.009; diastolic, from
62⫾1 to 59⫾1 mm Hg, P⫽0.02).
Conclusions—These data suggest that in patients with CHF, slow breathing, in addition to improving oxygen saturation
and exercise tolerance as has been previously shown, may be beneficial by increasing baroreflex sensitivity.
(Circulation. 2002;105:143-145.)
Key Words: baroreflex 䡲 heart failure 䡲 heart rate 䡲 blood pressure 䡲 respiration
T
he protective role of a preserved arterial baroreflex in
patients with chronic heart failure (CHF) or with previous myocardial infarction is now well established,1,2 and in
recent years much attention has been paid to those drugs (eg,
scopolamine, pirenzepine, ACE inhibitors3,4) and to those
interventions (eg, physical exercise5) that are able to increase
the vagal tone or the baroreflex sensitivity. A slow rate of
breathing (in the range of 6 breaths/min) has several favorable effects on the cardiorespiratory system in patients with
CHF: It increases resting oxygen saturation, improves ventilation/perfusion mismatching, and improves exercise tolerance by reducing the sensation of dyspnea;6 it also reduces
chemoreflex activation7 and muscle nerve sympathetic activity.8 Whether slow breathing has any effect on arterial
baroreflex sensitivity in heart failure, however, is still
unknown.
The aim of this study, therefore, was to assess whether the
arterial baroreflex can be enhanced by a slow rate of
breathing (6 breaths/min) in healthy subjects and in patients
with CHF. This may have practical implications because this
breathing pattern can be easily learned by patients with CHF.6
Methods
We studied 81 patients with stable CHF (no changes in their signs
and symptoms within the 2 weeks before examination) and 21
healthy controls. The protocol of the study was approved by local
ethics committees, and all subjects gave informed consent to participate in the study. Exclusion criteria were the presence of atrial
fibrillation, pulmonary diseases, or a smoking history in the previous
2 years. Clinical data for CHF patients and controls are shown in the
Table. Recordings of ECG, respiration (Respitrace), and blood
pressure (Pilot model, Colin Tonometry) were obtained during 5
minutes of spontaneous breathing, 4 minutes of controlled breathing
at 15 breaths/min (ie, similar to the spontaneous breathing rate; for
the purpose of verifying the effect of simple regularization of
breathing rate), and 4 minutes of controlled breathing at 6
breaths/min.
Arterial baroreflex sensitivity was measured by spectral analysis
using the “␣-angle” method.9 Briefly, the gain of the arterial
baroreflex was obtained by dividing the amount of fluctuation in the
RR interval by the fluctuations of systolic blood pressure at the same
frequency (respiration-synchronous and slow, nonrespiratory oscillations during spontaneous and controlled breathing at 15 breaths/
min; 6 breaths/min unique oscillatory component during slow
breathing). A mathematical function (squared coherence) was used
to prove that fluctuations in the RR interval are in fact related to
similar fluctuations in blood pressure. This approach gives results
comparable to those obtained with the Oxford phenylephrine test.
Received August 30, 2001; revision received November 19, 2001; accepted November 26, 2001.
From the Department of Internal Medicine, University of Pavia and IRCCS Ospedale S Matteo, (L.B., C.P.), Pavia, Italy; the Institute of Respiratory
Diseases, University of Catania (L.S.), Catania, Italy; First Department of Cardiology, University of Gdansk (J.B.), Gdansk, Poland; Herz-Zentrum (G.M.,
A.W.F.), Bad Krozingen, Germany; the Chinese University of Hong Kong, Prince of Wales Hospital (L.Y.C.Y., J.E.S.), Hong Kong SAR; the Department
of Cardiology, IRCCS Fondazione Salvatore Maugeri, Centro Medico Tradate (R.P.), Tradate, Italy; and the Department of Cardiology, IRCCS
Fondazione Salvatore Maugeri, Centro Medico Pavia (R.T.), Pavia, Italy.
Correspondence to Luciano Bernardi, MD, Clinica Medica 1, Universita’ di Pavia, IRCCS Ospedale S Matteo, 27100 Pavia, Italy. E-mail
[email protected]
© 2002 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
143
144
Circulation
January 15, 2002
Characteristics of the Subjects
Patients
with CHF
Controls
81
21
Age, y
58⫾1
55⫾2
Weight, kg
75⫾2
68⫾3
NS
Height, cm
170⫾1
169⫾2
NS
Body mass index, kg/m2
25.7⫾0.4
23.2⫾0.8
⬍0.01
I
6
䡠䡠䡠
II
33
䡠䡠䡠
III
27
䡠䡠䡠
IV
15
䡠䡠䡠
Coronary artery disease
40
䡠䡠䡠
Dilated cardiomyopathy
25
䡠䡠䡠
Valvular disease
3
䡠䡠䡠
Hypertensive
3
䡠䡠䡠
Idiopathic
3
䡠䡠䡠
Other causes
7
䡠䡠䡠
23.5⫾1.3
䡠䡠䡠
ACE inhibitors
62
䡠䡠䡠
Digitalis
41
䡠䡠䡠
Diuretics
57
䡠䡠䡠
Nitrates
46
䡠䡠䡠
␤-Blockers
32
䡠䡠䡠
n
P*
NS
NYHA class
Diagnosis
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Figure 1. Effect of breathing rate on baroreflex sensitivity.
*P⬍0.0001 vs controls; †P⬍0.0025 vs spontaneous breathing;
§P⬍0.025 vs 15 breaths/min; ‡P⬍0.0005 vs 15 breaths/min.
Echographic evaluation
Fractional shortening, %
Current Therapy
Calcium antagonists
7
䡠䡠䡠
Amiodarone
30
䡠䡠䡠
Angiotensin II inhibitors
14
䡠䡠䡠
Values are mean⫾SEM or number.
*Differences between CHF and controls by unpaired t test.
Comparison of variables at different breathing rates and in the 2
groups was done by analysis of variance for mixed design (factorial
model for differences between groups, repeated measures for differences between breathing rates); comparisons between different
NYHA classes were made by a factorial design analysis of variance.
If overall significance (P⬍0.05) was observed, then Sheffe’s test was
used to assess differences between different breathing patterns or
between different NYHA classes.
(Figure 1). Subjects with milder CHF tended to have greater
baroreflex sensitivity. The overall intergroup differences,
however, were not significant (baroreflex sensitivity during
spontaneous breathing: NYHA class I, 6.8⫾1.4; II, 5.2⫾0.5;
III, 5.0⫾0.7; and IV,: 3.9⫾0.5 ms/mm Hg; during breathing
at 6 breaths/min: NYHA class I, 9.3⫾1.9; II, 6.0⫾0.6; III,
6.2⫾0.9; and IV, 4.8⫾1.2 ms/mm Hg). The increase in
baroreflex sensitivity in CHF patients during breathing at 6
breaths/min remained lower compared with the increase
observed in controls, and it correlated positively with the
value obtained during spontaneous breathing (r⫽⫹0.202,
P⫽0.047). The effect of controlling the breathing rate at a
frequency similar to that of spontaneous breathing (15
breaths/min) did not induce significant changes in baroreflex
sensitivity (Figure 1). The slow breathing rate in the CHF
group also produced an increase in mean RR interval of 20 ms
and a decrease in both systolic and diastolic blood pressure
(systolic, from 117⫾3 to 110⫾4 mm Hg, P⫽0.009; diastolic,
from 62⫾1 to 59⫾1 mm Hg, P⫽0.02) (Figure 2). No
changes were observed during controlled breathing at 15
breaths/min compared with spontaneous breathing.
Results
Discussion
During spontaneous breathing (breathing rates were
16.2⫾0.5 and 13.5⫾1.1 breaths/min in CHF patients and
controls, respectively [P⫽0.021]), heart rate variability and
baroreflex sensitivity were depressed in CHF patients compared with the controls (the SD of RR intervals was 23.5⫾2.3
versus 41.9⫾2.8 ms, respectively, P⫽0.0002). Breathing at 6
breaths/min, compared with spontaneous breathing, slightly
increased overall spontaneous fluctuations in RR interval,
reduced fluctuations in blood pressure, and significantly
increased the baroreflex sensitivity in both CHF patients
(from 5.0⫾0.3 to 6.1⫾0.5 ms/mm Hg, P⬍0.0025) and controls (from 9.4⫾0.7 to 13.8⫾1.0 ms/mm Hg, P⬍0.0025)
Baroreflex sensitivity can be enhanced significantly by slow
breathing, both in health and in the presence of CHF. This
seems to occur through a relative increase in vagal activity
and a reduction in sympathetic activity, as could be argued by
the small reduction in heart rate observed during slow
breathing and by the reduction in both systolic and diastolic
blood pressures. The increase in tidal volume, which compensates for the reduced breathing rate in order to maintain
minute ventilation,6,8 could be responsible for these autonomic changes through a reduction in sympathetic activity8 or
via the Hering-Breuer reflex. In fact, sympathetic activity was
found to increase with faster breathing rates and to decrease
Bernardi et al
Baroreflex and Slow Respiration
145
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Figure 2. Effect of breathing rate on RR interval and blood pressure. *P⬍0.05 and **P⬍0.01 vs spontaneous breathing.
skewed distribution, but it indicates that even a small increase
with respect to a low initial value is clinically important.11
It is noteworthy that this improvement in baroreflex sensitivity was obtained by simply modifying the breathing
pattern without administration of any drug; yet the extent of
the increase in baroreflex sensitivity that we observed was
similar to that obtained with captopril in patients with CHF.4
It remains to be assessed whether these changes persist after
resuming normal respiration. However, the slow breathing
pattern is well tolerated by the patients; carbon dioxide is
maintained within resting values, and the chemoreflex activity is not stimulated by this breathing rate.7 Because it does
not stimulate ventilation, which may be deleterious in subjects who already have a tendency to hyperventilate, this
pattern could be maintained as spontaneous and could be
learned by appropriate training.6 Slow breathing has been
found to improve resting oxygen saturation, and, possibly
because of an enhanced mobilization of respiratory muscles
and diaphragm, it may improve exercise capacity through a
delayed onset of dyspnea and fatigue.6
In conclusion, we have described a new, simple, and
inexpensive method to increase the baroreflex sensitivity and
vagal activity in patients with heart failure, which also
increases oxygen saturation, improves the ventilation efficiency and the exercise tolerance (as previously described6),
and reduces sympathetic overactivity.8 Practicing slow and
deep breathing thus can be beneficial in heart failure or in
other diseases (eg, coronary disease) in which impaired
baroreflex sensitivity may have adverse prognostic value.
with higher tidal volumes in CHF.8,10 The increase in baroreflex sensitivity depended on the slow breathing rate and not
on the regularization obtained by controlling the breathing,
inasmuch as this effect was not evident when breathing was
controlled at a frequency (15 breaths/min) similar to the
spontaneous rate. The reduction in blood pressures observed
during slower and deeper respiration (Figure 2) confirms that
this finding is the consequence of a reduced afterload,
perhaps secondary to reduced sympathetic activity,8 rather
than worsening of pump function. This more favorable
sympathovagal balance also may be linked to a reduction of
chemoreflex overactivity due to the reciprocal influences of
these 2 reflexes.11 The chemoreflex actually is reduced by the
slow breathing,7 thus adding another favorable effect on
CHF.
In accordance with previous reports, the baroreflex sensitivity in patients with CHF under basal conditions was lower
than that of controls, and the extent of the increase observed
during slow breathing was smaller in the patients with CHF
than in the controls. Interestingly, subjects with lower values
at baseline tend to have smaller changes, whereas those with
higher values show proportionally greater changes (as evidenced by the correlation between resting values and the
increase induced by slow breathing); this probably is connected to the fact that reflex sensitivity shows a slightly
1. Mortara A, LaRovere MT, Pinna GD, et al. Arterial baroreflex modulation of heart rate in chronic heart failure. Circulation. 1997;96:
3450 –3458.
2. LaRovere MT, Bigger JT Jr, Marcus FI, et al. Baroreflex sensitivity and
heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet. 1998;351:478 – 484.
3. Casadei B, Pipilis A, Sessa F, et al. Low dose scopolamine increase
cardiac vagal tone in the acute phase of myocardial infarction. Circulation. 1993;88:353–357.
4. Osterziel KJ, Rohring N, Dietz R, et al. Influence of captopril on the
arterial baroreceptor reflex in patients with heart failure. Eur Heart J.
1988;9:1137–1145.
5. Coats AJ, Adamopoulos S, Radaelli A, et al. Controlled trial of physical
training in chronic heart failure: exercise performance, hemodynamics,
ventilation, and autonomic function. Circulation. 1992;85:2119 –2131.
6. Bernardi L, Spadacini G, Bellwon J, et al. Effect of breathing rate on
oxygen saturation and exercise performance in chronic heart failure.
Lancet. 1998;351:1308 –1311.
7. Spicuzza L, Gabutti A, Porta C, et al. Yoga and chemoreflex response to
hypoxia and hypercapnia. Lancet. 2000;356:1495–1496.
8. Goso Y, Asanoi H, Ishise H, et al. Respiratory modulation of muscle
sympathetic nerve activity in patients with chronic heart failure. Circulation. 2001;104:418 – 423.
9. Malliani A, Pagani M, Lombardi F, et al. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;84:482– 492.
10. Naughton MT, Floras JS, Rahman MA, et al. Respiratory correlates of
muscle sympathetic nerve activity in heart failure. Clin Sci. 1998;95:
277–285.
11. Ponikowski P, Chua TP, Piepoli M, et al. Augmented peripheral chemosensitivity as a potential input to baroreflex impairment and autonomic
imbalance in chronic heart failure. Circulation. 1997;96:2586 –2594.
References
Slow Breathing Increases Arterial Baroreflex Sensitivity in Patients With Chronic Heart
Failure
Luciano Bernardi, Cesare Porta, Lucia Spicuzza, Jerzy Bellwon, Giammario Spadacini, Axel W.
Frey, Leata Y.C. Yeung, John E. Sanderson, Roberto Pedretti and Roberto Tramarin
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Circulation. 2002;105:143-145
doi: 10.1161/hc0202.103311
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2002 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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http://circ.ahajournals.org/content/105/2/143
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