heart failure is a complex , multisystem condition resulting in inadequate blood supply to 
 meet the metabolic needs of tissues in the presence of normal venous return , or can only 
 meet such needs with higher than normal filling pressures1.the hemodynamic changes commonly found in heart failure involve 
 inadequate cardiac output and an increase in both pulmonary and systemic venous pressure . 

compromised cardiac output is apparent with varying degrees during exercise and , in its most 
 severe form , is observed in the resting state1 .
such changes in heart function generally lead to multiple 
 hospitalizations , often with the need for mechanical ventilation . at some point after the initial insult of compromised cardiac function in heart failure , a 
 chronic heightened activation of the sympathetic nervous system occurs , leading to an 
 imbalance in autonomic tone , a shift away from vagal activity , that further contributes to 
 and accelerates cardiac dysfunction2,3,4 . on 
 the other hand , variations in alveolar and intrathoracic pressures as well as the activity 
 of pulmonary receptors through the use of positive airway pressure modulate autonomic tone , 
 specifically increasing vagal activity5 . 

increased non - cholinergic and non - adrenergic vagal activation induced by positive airway 
 pressure is also associated with coronary vasodilatation through activation of vasoactive 
 intestinal peptides6 , 7 .
lastly , the magnitude of positive airway pressure used influences 
 the degree to which hemodynamics , efferent vagal activity and heart rate are impacted8 , 9 in the literature , parati and esler3 
 reported continuous positive airway pressure ( cpap ) is a viable non pharmacological option 
 for sympathetic inhibition .
yoshida et al.10 suggest that the administration of cpap combined with support 
 pressure is more effective than cpap alone at achieving an increase in the cardiac index and 
 this improvement may be related to a combination of both neural and mechanical effects , such 
 as a reduction in ventricular preload .
given the obvious effects heart failure has on autonomic balance in hf , research examining 
 the ability of positive airway pressure to improve this physiologic abnormality would be 
 beneficial .
thus , the aim of the present study was to investigate autonomic modulation in 
 hospitalized patients with heart failure submitted to acute treatment with bilevel positive 
 airway pressure ( bipap ) during noninvasive ventilation .
our hypothesis was that the 
 administration of bipap during noninvasive ventilation would result in a beneficial 
 autonomic response in hospitalized patients with heart failure .
a prospective , cross - sectional study was carried out at the semi - intensive care unit of the 
 albert einstein israelita hospital following approval from the human research ethics 
 committee of the albert einstein teaching and research institute ( sao paulo , brazil ) under 
 process n 263/2011 .
all patients received information regarding the objectives of the study 
 and gave their consent to participation by signing a statement of informed consent .
all were invited to 
 participate in the protocol , but only those who consented participated the sample was selected consecutively with the following inclusion criteria : age 18  years 
 or older ; clinical diagnosis of decompensated heart failure ; use of noninvasive ventilation ; 
 a left ventricular ejection fraction less than 50% confirmed by echocardiography ; and new 
 york heart association classification i - iv .
the following were the exclusion criteria : 
 coexisting chronic respiratory disease ; unstable angina ; second or third degree 
 atrioventricular block ; supraventricular tachycardia , frequent premature ventricular 
 contractions , atrial flutter or atrial fibrillation ; bronchodilator therapy ; and incapacity 
 or refusal to perform the proposed protocol .
after applying the inclusion and exclusion 
 criteria , 20 subjects were included in the study .
data collection of subject characteristics involved review of clinical history , and 
 confirmation of previous medical diagnoses and medication use
. heart rate ( hr ) and the 
 interval between consecutive heart beats ( r - r interval ) were determined at rest with and 
 without the use of bipap during noninvasive ventilation .
a polar rs 800cx monitor ( polar electro oy , kempele , finland ) was used for the acquisition 
 of hr and the r - r interval data for the subsequent analysis of heart rate variability ( hrv ) . 

the strap ( polar wearlink heart rate transmitter ) was attached to the patient s thorax over 
 the lower third of the sternum .
data recordings were always performed in the afternoon with 
 the patient conscious within 72 hours of admission to hospital in a room with the 
 temperature controlled at 21 c. no patient had ingested any food or liquid prior to the 
 procedure .
the data recording began during spontaneous breathing for ten minutes and continued while 
 with the patient at rest received bipap ( vision , respironics / philiphs , usa ) in 
 spontaneous / time mode , with positive inspiratory airway pressure of 20 cmh2o11 and positive expiratory airway pressure of 
 10 cmh2o12 for 30 minutes 
 using a full face mask ( respironics ) .
after the withdrawal of bipap , hr and irr were 
 determined for an additional 10 minutes , a total of 50 minutes of recording . during the 
 evaluation , peripheral oxygen saturation ( spo2 ) ,
blood pressure and respiratory 
 rate ( vf ) were displayed on a monitor ( intellivue mp70 anesthesia , philips medizinsysteme , 
 boeblingen , germany ) and recorded .
the hr and r - r interval data were imported by the polar precision performance program and 
 exported as txt files .
all ectopic heartbeats or artifacts from signal 
 movements were analyzed through a visual inspection of the computer screen .
r - r intervals 
 that differed by  20 bpm from the mean of the period analyzed were manually excluded . only 
 segments with more than 90% pure sinus beats were included in the final analysis .
at least 
 256 r - r intervals from the most stable sessions were selected and analyzed with the aid of 
 the kubios hrv analysis program 2.0 for windows ( biomedical signal and medical imaging 
 analysis group , department of applied physics , university of kuopio , finland)13 hrv was analyzed using three linear measures in the time and frequency domains .
mean hr and 
 mean r - r interval data , standard deviation of the mean of all r - r intervals ( stdrr ) and the 
 square root of the sum of the square of the differences between r - r intervals divided by the 
 number of r - r intervals in a determined time minus 1 ( rmssd ) were computed as measures of 
 the time domain .
hrv was calculated in the frequency domain using fast fourier transforns , 
 with evaluations of the low frequency ( lf ) and high frequency ( hf ) indices in normalized 
 units and the lf / hf ratio14 .
nonlinear measures were also used for the detrended fluctuation analysis ( dfa ) as an 
 exponent of the short - term scale (  11 beats ; dfa1 ) in a set of r - r data .
a poincar graph 
 was used to obtain the standard deviations perpendicular ( sd1 ) and parallel ( sd2 ) to the 
 identity line of the r - r intervals14,15,16 .
the sample size ( 20 
 patients ) was calculated to yield an 80% power and  = 0.05 , using the lf component of 
 autonomic activity as the outcome17 .
the 
 shapiro - wilk test was used to examine the parametric distribution of baseline 
 characteristics , which were expressed as mean and standard deviation values .
anova with 
 tukey s post hoc test was used for comparisons between different evaluations , and 
 significance was accepted for values of p < 0.05 .
twenty - six patients were received evaluations , and six of them were excluded ( 3 exhibited 
 high - response arterial fibrillation , 2 exhibited claustrophobia and 1 did not complete the 
 study ) .
table 1table 1.demographic , anthropometric and clinical characteristicsvariableic ( n = 20)anthropometric characteristicsage ( years)69.0  8.0height ( m)1.65  0.8body mass ( kg)67.0  8.0bmi ( kg / m)24.5  0.6class nyhai20%ii15%iii40%iv25%echocardiographyejection fraction of the left ventricle ( % ) 36  7cause of heart failuredilated cardiomyopathy 60%idiopathic dilated cardiomyopathy 40%medication - patients ( % ) beta - blocker17 ( 85%)digoxin7 ( 35%)nitrato3 ( 15%)angiotensin - converting enzyme inhibitors17 ( 85%)furosemide7 ( 35%)acetylsalicylic acid3 ( 15% ) displays the demographic , anthropometric and clinical data of the sample ( n = 
 20 ) .
table 2table 2.physiological parameters obtained before , during and after application of bipap 
 for patients with hfic ( n = 20)pre bipapduring bipap post bipaprr ( rpm)164145136sbp ( mmhg)1451413816 * 12513spo2 ( % ) 913942 * 963rr : respiratory rate , sbp : systolic blood pressure , spo2 : peripheral 
 oxygen saturation , bipap : bilevel positive airway pressure . *
significant ( p<0.05 ) difference between pre and during bipap ; 
 significant ( p<0.05 ) difference between during and after bipap ; 
 significant ( p<0.05 ) difference between pre and post bipap displays the physiological variables ( vf , blood pressure and spo2 ) 
 evaluated before ( baseline ) , during and after the administration of bipap .
no significant 
 differences in vf were found among the conditions . a significant reduction in systolic blood 
 pressure was found during and after noninvasive ventilation in comparison to the baseline 
 evaluation .
moreover , an increase in spo2 was found during and after bipap in 
 comparison with the baseline evaluation .
rr : respiratory rate , sbp : systolic blood pressure , spo2 : peripheral 
 oxygen saturation , bipap : bilevel positive airway pressure .
* significant ( p<0.05 ) difference between pre and during bipap ; 
 significant ( p<0.05 ) difference between during and after bipap ; 
 significant ( p<0.05 ) difference between pre and post bipap table 3table 3.linear and nonlinear heart rate variability indices evaluated before , during and 
 after application of bipap in patients with hfic ( n = 20)pre bipapduring bipappost bipaplinear hrvmean rr ( ms)782.6115.4814.6116.6790.1112.0stdrr ( ms)30.994.440.36.2 * 53.312.5mean hr ( 1/min)71.411.677.211.7 * 86.513.2rmssd ( ms)14.910.217.22.9 * 23.55.7lfun74.910.464.212.973.99.28hfun25.110.235.811.8 * 27.49.8lf / hf ratio3.92.72.21.5 * 3.21.4hrv nonlinearsd1 ( ms)8.314.312.95.8 * 22.86.3sd2 ( ms)50.67.647.710.0 * 70.317.7dfa10.920.51.140.5 * 0.790.31data presented as mean  sd .
bipap : bilevel positive airway pressure , rr : rr 
 interval , stdss : standard deviation of the average of all r - ri , hr : heart rate , rmssd : 
 square root of the sum of the squared differences between rr , lf : low frequency , hf : 
 high frequency , sd : standard deviation , dfa : analysis of fluctuations purified 
 trend .
* significant ( p<0.05 ) difference between pre and during bipap ; 
 significant ( p<0.05 ) difference between during and after bipap ; 
 significant ( p<0.05 ) difference between pre and post bipap displays autonomic modulation based on linear and nonlinear indices of hrv 
 obtained at rest before , during and after bipap .
significantly higher indices representative 
 of parasympathetic activity were found in the time and frequency domains as well as in the 
 nonlinear poincar analysis ( rmssd , hf , sd1 ) during and after bipap in comparison with the 
 baseline evaluation .
bipap : bilevel positive airway pressure , rr : rr 
 interval , stdss : standard deviation of the average of all r - ri , hr : heart rate , rmssd : 
 square root of the sum of the squared differences between rr , lf : low frequency , hf : 
 high frequency , sd : standard deviation , dfa : analysis of fluctuations purified 
 trend .
* significant ( p<0.05 ) difference between pre and during bipap ; 
 significant ( p<0.05 ) difference between during and after bipap ; 
 significant ( p<0.05 ) difference between pre and post bipap
the present study assessed the effects of bipap on autonomic tone in patients hospitalized 
 secondary to decompensated heart failure .
the major finding was that acute treatment with 
 bipap resulted in a favorable autonomic adjustment in these patients , increasing vagal 
 activation , as demonstrated by the higher hrv indices related to parasympathetic activity 
 ( rmssd , hf and sd1 ) .
these findings have important clinical implications given prior 
 evidence indicates increased parasympathetic tone protects the heart from arrhythmias 
 induced by an electrophysiological imbalance18 .
certainly this treatment goal is relevant and of importance for 
 patients with decompensated heart failure .
the lowest lf and lf / hf ratio during the brief bipap intervention in comparison to 
 spontaneous breathing also demonstrated the positive effect of this noninvasive ventilation 
 approach , as these indices are related to sympathetic activity , which is associated with 
 cardiac electrical instability , platelet aggregation , coronary vasoconstriction and greater 
 stress on the wall of the myocardium19 , 20 . as hf and rmssd
are considered markers of 
 vagal modulation and lf is associated with sympathetic activity21 , an increase in sympathetic activity and reduction in 
 parasympathetic activity are associated with arrhythmia and an increased risk of death2 , 21 , 22 .
thus , the present findings demonstrate 
 the benefits of bipap in patients with decompensated heart failure regarding these 
 aspects .
the overall improvement in hrv ( stdrr , sd2 ) after certain interventions has been associated 
 with a reduction in cardiovascular risk20 .
consequently , it is reasonable to assume that the administration of 
 bipap promoted the stimulation of vagal tone .
it should be noted that only the acute 
 response was evaluated in the present study and the longer - term effects are unknown .
future 
 studies should examine the impact of a longer bipap intervention on the maintenance of 
 autonomic tone .
low nonlinear indices of hrv ( denominated dfa ) are associated with a greater likelihood of 
 adverse cardiac events and death .
ksela et al.23 found a greater frequency of arrhythmia in patients with a lower 
 dfa. in the present study , the increase in dfa during bipap suggests a reduction in the 
 risk of developing arrhythmia .
autonomic activity in the heart ( as evaluated by hrv ) is depressed in patients with heart 
 failure2 , 24 , and is associated with a greater mortality rate among such 
 patients . indeed , depressed autonomic activity is a predictor of hemodynamic impairment , 
 death due to progressive cardiac dysfunction heart failure and sudden death25,26,27,28 . 

thus , positive airway pressure is commonly used during the hospitalization of patients with 
 heart failure and the present findings demonstrate that this benefit goes beyond the 
 hemodynamic response to also include a favorable neural response of the autonomic nervous 
 system .
these findings are in agreement with data described by panatoni et al.29 in a study involving hospitalized patients 
 following re - vascularization surgery of the myocardium , in which cpap also positively 
 affected autonomic heart function .
it is necessary to understand the connections of the autonomic nervous system , respiratory 
 system and heart to offer adequate care for patients with heart failure .
moreover , it is of 
 the utmost importance to know that these systems exert effects on one another .
thus , in 
 order to optimize treatment and outcomes , all of the aforementioned systems should be 
 targeted with proven effective interventions . in terms of hemodynamics ,
haruki et al.30 evaluated the 
 administration of adaptive servoventilation for patients with heart failure and found a 
 reduction in post - load , increases in cardiac output and systolic volume as well as a 
 beneficial effect on ventricular remodeling and left ventricular function , along with a 
 reduction in mitral valve regurgitation . while no evaluation was performed in the present 
 study of the autonomic response in cpap mode without support pressure , a previous study by 
 our research group evaluated this aspect and found a better autonomic response with cpap of 
 10 cmh2o .
autonomic dysfunction with an increase in sympathetic activity and a reduction in 
 parasympathetic activity has been reported in patients with heart failure .
this dysfunction 
 is associated with arrhythmia and an increased risk of adverse cardiovascular events and 
 death31 .
noninvasive ventilation has 
 been widely used as an effective support during convalescence in this population because it 
 improves ventilatory and hemodynamic variables as well as autonomic balance .
the findings of 
 the present study demonstrate that bipap also promotes different autonomic responses . 

further studies are needed to evaluate the autonomic balance elicited by the chronic use of 
 noninvasive ventilation in these patients .
the main limitation of this study was the lack of a control group receiving cpap without 
 support pressure .
this was not approved by the ethics committee due to the fact that the 
 hemodynamic response of cpap is individualized for each patient with heart failure .
another 
 limitation of the present study was the non - standardization of the use of medications , as it 
 was not possible to intervene in the therapeutic approach prescribed by the medical 
 team .
the present findings demonstrate that bipap results in beneficial autonomic responses due 
 to vagal activation in patients with heart failure who were hospitalized for acute 
 decompensation .
 [ purpose ] this study evaluated the effect of bilevel positive airway ( bipap ) on the 
 autonomic control of heart rate , assessed by heart rate variability ( hrv ) , in patients 
 hospitalized with decompensated heart failure . [ subjects and methods ] this prospective 
 cross - sectional study included 20 subjects ( age : 698  years , 12 male , left ventricular 
 ejection fraction : 36 8% ) diagnosed with heart failure who were admitted to a 
 semi - intensive care unit with acute decompensation . 
 date was collected for hrv analysis 
 during : 10 minutes spontaneous breathing in the resting supine position ; 30 minutes 
 breathing with bipap application ( inspiratory pressure = 20 cmh2o and 
 expiratory pressure = 10 cmh2o ) ; and 10 minutes immediately after removal of 
 bipap , during the return to spontaneous breathing . 
 [ results ] significantly higher values 
 for indices representative of increased parasympathetic activity were found in the time 
 and frequency domains as well as in nonlinear poincar analysis during and after bipap in 
 comparison to baseline . 
 linear hrv analysis : standard deviation of the average of all r - r 
 intervals in milliseconds = 30.994.4 pre , 40.36.2 during , and 53.312.5 post bipap . 
 
 non - linear hrv analysis : standard deviations parallel in milliseconds = 8.314.3 pre , 
 12.95.8 during , and 22.8 6.3 post bipap . 
 [ conclusion ] the present findings demonstrate 
 that bipap enhances vagal tone in patients with heart failure , which is beneficial for 
 patients suffering from acute decompensation . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION