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Cardiac Autonomic Modulation in Tetralogy of
Fallot
Ana M. D. S. Antônio1 MSc, Diego L. China2 MSc , Renan Shida2 MSc , Juliana C. Barbosa1 MSc,
Viviani Barnabé3PhD, Luiz Carlos de Abreu4MD, Vitor E. Valenti*1MD
Abstract
Studies have shown that patients with tetralogy of Fallot
present impaired heart function. Such changes in cardiac
system remain several years after the surgery, and could be
related to markers of sustained ventricular tachycardia
and sudden death. Herein, we aimed to describe the cardiac
autonomic regulation in tetralogy of Fallot. To perform the
review the articles used in this study were selected in
Pubmed, Medline, Lilacs and SciELO. For this search we
crossed the following keywords: tetralogy of Fallot,
autonomic nervous system, reconstructive surgery, heart
rate variability, which were defined based on descriptors of
health Headings (MeSH). We found that, in general,
patients with operated tetralogy of Fallot have changes in
cardiac autonomic modulation after several years elapsed
from reconstructive surgery, and they presented higher
activation of the sympathetic ANS which can be associated
ventricular arrhythmias. In conclusion, we observed that
the patients have a reduced heart rate variability years
after the correction surgery.
I. INTRODUCTION
T
etralogy of Fallot is a cyanotic heart defect. The main
cause of late death is sudden cardiac death, usually caused
by ventricular tachycardia, pulmonary regurgitation and right
ventricular dilatation1,2. The reconstructive surgery aims to
rebuild the track from the aorta and the pulmonary stenosis and
fixes the defect of the interventricular canal.
Currently, there is an expectation of good surgical outcomes
in patients undergoing repair of tetralogy of Fallot with the
evolution of surgical techniques and intensive care
postoperatively, with the possibility of correction in early life.
After surgery of repair tetralogy of Fallot the chance of survival
is 94%3. However, these patients have compromised the
effectiveness and functionality of the heart 4.
In this sense, the autonomic nervous system (ANS) plays an
indispensable role in the regulation of physiological processes
in the human body during normal and pathological conditions.
Among the techniques used in its evaluation, the heart rate
variability (HRV) has emerged as a simple and noninvasive
measure of autonomic impulses. HRV describes the
oscillations in the interval between consecutive heart beats (RR
interval), as well as oscillations between instantaneous heart
rates consecutives 5-7. Low HRV in patients with heart disease
is a strong predictor of ventricular arrhythmias and sudden
death 8. Furthermore, there is a strong correlation between the
reduced HRV and sudden death after myocardial infarction 9,10.
Impaired autonomic function may be relevant to the increased
incidence of sudden death after repair of tetralogy of Fallot.
Given the importance of identifying changes induced by
surgical repair of tetralogy of Fallot on the autonomic nervous
system, we sought to bring together studies that addressed the
analysis HRV in individuals who had surgical repair of
tetralogy of Fallot to better understand the cardiac autonomic
regulation in this population, and to provide an update of the
findings published concerning this topic. Thus, we aimed to
describe the cardiac autonomic regulation in tetralogy of Fallot.
Keywords - Tetralogy of Fallot; Autonomic nervous system;
cardiovascular system.
Cite this article as: Antônio AMS, China DL, Shida R, Barbosa
JC, de Abreu LC, , Valenti VE. Modulation Cardiac Autonomic
in Tetralogy of Fallot. Literature. JCvD 2015. In Press
Received on 15 April 2014.
From 1Center for the Study of Nervous System (CESNA), Graduate Program in
Physical Therapy, Faculty of Technology Sciences, UNESP, Presidente
Prudente, SP, Brazil. 2Graduate Program in Cardiorespiratory Physiotherapy,
University of Marília, UNIMAR, Marília, SP, Brazil. 3Department of
Environmental Health, Harvard Medical School of Public Health, Boston, MA,
EUA. 4Department of Morphology and Physiology, Faculty of Medicine of
ABC, Santo André, SP, Brazil.
Conflict of Interest: none declared.
*Corresponding Author: [email protected]
II. METHODS
The articles used in this study were selected in Pubmed,
Medline, Lilacs and SciELO. For this search we crossed the
following keywords: Tetralogy of Fallot, autonomic nervous
system, reconstructive surgery, heart rate variability, which
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JOURNAL OF CARDIOVASCULAR DISEASE
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VOL.X NO.X
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were defined based on descriptors of health Headings (MeSH).
The studies were selected based on their titles and were
analyzed by a single researcher, selected according to the
inclusion criteria established for this review. For this, the title
should expressed focus on the study: heart rate variability in
patients with tetralogy of Fallot corrected autonomic control
after surgical repair of tetralogy of Fallot, correlation between
heart rate variability and ventricular tachycardia.
After that, it was made a filtering of the results to identify
repetitions, as was done in the search various databases. All
titles chosen had their abstracts studied in order to select the
articles that addressed cardiac autonomic regulation in patients
with tetralogy of Fallot corrected. Abstracts that approached
this theme had their full texts read. The selected studies had
their references analyzed to identify relevant studies that were
not found in the electronic search.
Studies published between the period 2000-2014, in
Portuguese, Spanish, and English, who had made the correction
of tetralogy of Fallot, and analyzed the autonomic nervous
system with HRV were included, and all were included types of
study design. For the assessment of the methodological quality
of the studies PEDro scale was used. Data were qualitatively
described and tabulated according to the authors and year of the
study population characteristics, purpose of the study, observed
index and conclusions observed.
Moreover, the reduction in cardiac output may lead to an
increase in sympathetic activity by baroreflex activation and
alter ventricular kinematics14.
Daliento and coworkers15 verified reduction of SDNN index
compared with the control group, and a positive correlation
between myocardial scintigraphy and the value of SDNN
index, reflecting sympathetic predominance in operated
individuals. In this context, significantly reduced value of
SDNN in patients with ventricular arrhythmias found in their
study suggests an influence of the activity of the autonomic
nervous system on ventricular electrical instability.
Davos et al11 found in some patients an overall impairment of
cardiac autonomic modulation few years after repair of
tetralogy of Fallot. The patients investigated showed reduced
HRV and baroreflex sensitivity. Both indices in the time
(SDNN and RMSSD), and frequency domain (LF and HF)
were reduced compared to the healthy control group, clearly
indicating the difference in HRV. In patients who had
undergone surgical correction, there was reduction of HRV
because of sinus node dysfunction HRV, which is very frequent
in patients with congenital heart disease. Furthermore, it was
also observed an increased sympathetic tone on the hart,
regardless of the value of the heart rate, which reflects the
lowest values of SDNN 14.
McLeod and collaborators 16 reported a reduction in
parasympathetic index (pNN50) associated with ventricular
dilation and right ventricular hypertension in young, ten years
after correction of tetralogy of Fallot. In this circumstance,
Lammers et al. 17 found a significant increase in all parameters
of HRV (SDNN, RMSSD, pNN50) and identified the SDNN
index as the best predictor variable, confirming the low HRV in
these patients. The LF component of spectral analysis, which
indicates the sympathetic and parasympathetic modulation
(with sympathetic predominance), was also associated with an
increased likelihood of hemodynamic and surgical
complications.
Heragu et al.18 found an association between the LF component
and the probability of having hemodynamic and surgical
complications i.e., the higher the value of the LF index, the
lower the possibility of negative event. The increased
sympathetic modulation may represent an important
compensatory mechanism for heart failure associated with a
reduced adrenergic discharge the neural sinus mode. Other
studies have found that the values of LF were associated with
reduced degree of heart failure in patients with congenital heart
diseases in adults, proving to be an important independent
predictor of sudden cardiac death in adults with impaired
cardiac 19. On the other hand, Butera et al12 noted that the HRV
indices were identical in both the preoperative group with
tetralogy of Fallot and post-operative group of other congenital
heart disease, but were significantly reduced in patients with
tetralogy of Fallot. In the group of patients with tetralogy of
Fallot indices of HRV (SDNN, RMSSD, pNN50, HF) were
significantly lower in patients with non-sustained ventricular
tachycardia compared with those without arrhythmias,
characterized by a reduction in vagal modulation. Kaltman et al
20
investigated newborns and found impairment of cardiac
autonomic control, which may be associated with prolonged
III. RESULTS
A. Search and selection strategy
Through the use of descriptors in the search of the databases
91 references were found. The first selection resulted in the
elimination of 69 titles, and the remaining studies passed to the
next stage of selection, which analyzed the content of their
abstracts and eliminated 14 abstracts, which did not meet the
established criteria. The remaining eight texts were read. The
elimination process excluded a total of 83 studies and we
considered 8 manuscripts for this review.
B. Characteristics of selected studies
These data are summarized in Table I, organized by authors
and year of publication, population characteristics, objectives,
indices evaluated and conclusions, contain eight articles
resulting from the systematic search.
IV. DISCUSSION
The aim of this study was to describe studies related to cardiac
autonomic regulation in tetralogy of Fallot. The selected texts
analyzed showed that in adult patients, which made surgical
repair of tetralogy of Fallot presented reduced HRV11-13, we
believe that this fact may be associated with hemodynamic
alterations. Patients after surgical repair of tetralogy of Fallot
still have a significant incidence of serious ventricular
arrhythmias that can be identified through the analysis of HRV.
Several factors induce changes in sympathetic and vagal
modulation in postoperative patients, the surgical incision may
involve the autonomic fibers, causing a heterogeneous
distribution of the efferent signal to the myocardium.
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hospital stays, and found a negative correlation between
SDNN, and LF RMSSD indices with the time in hospital.
A previous study analyzed HRV in children with pre-school
age and found no signs of cardiac autonomic dysfunction.
Aletti et al 4 evaluated HRV in children with congenital heart
disease, taking into account the effects of cyanotic and
acyanotic defects. The analysis showed that the values of LF
were significantly higher in children with pathological
condition compared to the control group, regardless of
cyanosis. These results suggested that children with congenital
heart disease may have lower HRV featured by sympathetic
hyperactivity and hemodynamic changes.
Another study found significant associations between HRV and
presence of morbidity and mortality in children and adolescents
undergoing surgical correction of congenital heart disease. The
authors observed imbalance of sympathetic and
parasympathetic modulation (LF / HF), the sympathetic
regulation appeared more active in relation to the
parasympathetic and this behavior persisted three months after
hospital discharge. The reduction of cardiac parasympathetic
modulation has also been demonstrated by other reduction
ratios. Three months after discharge, the RMSSD, pNN50 and
HF indices were reduced compared to preoperative period 21,22.
The literature has shown that physical exercise promotes
improvements in ANS modulation. However, other studies
have shown that physical exercise is recommended for
improving and maintaining cardiovascular health. The exercise
therapy is a non-pharmacological treatment that improves
cardiovascular fitness, quality of life, and controls autonomic
reflexes in patients with heart disease crônica23,24. Wyller et al
found after three months of exercise training significant
changes in HRV parameters, decrease LF and LF / HF ratio and
HF increased in the group with chronic heart failure as
compared to group control 25.When practiced in a planned and
regular physical exercise boosts the parasympathetic tone and
reduces sympathetic tone improves HRV in patients with
cardiac failure26.
We found no studies that evaluated the HRV after an
intervention of regular physical exercise protocol, but some
studies have found that despite the low exercise tolerance, these
patients have improved quality of life and clinical condition.
Dua et al , in their prospective study concluded that the practice
of simple physical activity such as walking regularly is
important , safe and significantly increases exercise capacity of
adult patients at all stages of congenital heart disease. It is also
useful to improve the quality of life by improving physical self perception, life satisfaction, levels of physical activity and
overall health27. Buys et al investigated the level of physical
activity of 73 adults with tetralogy of Fallot and concluded that
these patients are less active than the general population and
that inactivity contributes significantly to the reduction in
exercise capacity, and can worsen heart condition these
patients28. Silvilairat in their study found a significant
correlation between HRV and physical exercise capacity which
was assessed by peak oxygen uptake in 30 patients with TOF,
and found that the reduction in HRV associated with left
ventricular dysfunction are contributing factors for exercise
intolerance in these patients13. Additional studies investigating
physical exercise training for patients with tetralogy of Fallot is
necessary.
Our study has some points that deserve to be raised. We
decided to not select all the studies linking tetralogy of Fallot
with the autonomic nervous system in general, in order to
concentrate our goal to investigate the relationship between this
pathological condition and autonomic regulation of the heart.
Furthermore, studies on the involvement of non-linear HRV
indices were not found, we encourage further studies to
perform this analysis.
V. CONCLUDING REMARKS
In this review we present important data on cardiac autonomic
regulation in tetralogy of Fallot. It was observed that even years
after the correction surgery patients have impaired HRV. We
found no studies that assessed HRV after an intervention of a
physical exercise protocol. In patients with tetralogy of Fallot
corrected conducting studies on the influence of physical
training on the SNA these patients is required.
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Vitor E. Valenti. has completed his Ph.D at the
age of 27 years from Universidade Federal de São Paulo
(UNIFESP), São Paulo, SP, Brazil, he spent 5 months of his
doctoral fellowship at the School of Medicine of the University
of Utah, Salt Lake City, Utah, USA, and postdoctoral studies
from University of São Paulo (USP), São Paulo, SP, Brazil. He
has published more than 100 papers in reputed journals and
serving as an editorial board member of the African Journal of
Pharmacy and Pharmacology, Clinical Reviews and Opinion,
Asian Journal of Medical Science, Journal of Diabetes and
Endocrinology and Journal of Medical Laboratory and
Diagnosis. Currently, he is associate professor at the Faculty of
Phylosophy and Sciences, UNESP, Marí
lia, SP, Brazil.
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