幼童患有肥厚性心肌症Hypertrophic Cardiomyopathy者猝死機率較正常兒童高, 猝死前常有心律不整,可用HRV及LF/HF預測
Heart rate variability in children with hypertrophic
cardiomyopathy
Heart. 2003
February; 89(2): 205–206.
G Butera,* D Bonnet, J Kachaner, D Sidi, and E Villain
Pediatric Cardiology, Hôf.pital Necker Enfants Malades,
*Also Pediatric Cardiology, Istituto Policlinico, San Donato,
Correspondence to:
Dr Butera Gianfranco, Pediatric Cardiology, Istituto Policlinico San Donato, Via Morandi,30 - 20097 San Donato,
Milanese, Italy;
gianfra.but@lycos.com
Accepted July 25, 2002.
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Keywords: hypertrophic cardiomyopathy,
heart rate variability, children, sudden death
Hypertrophic cardiomyopathy (HCM) carries an increased risk of
sudden death, especially in children and young adults. We investigated heart
rate variability (HRV) in children with HCM, in order to evaluate its
prognostic value.
METHODS
Seventeen patients (9 males and 8 females) with non-obstructive HCM were
prospectively enrolled in the study. The diagnosis of HCM had been made between
the ages of 1 month and 13 years (mean (SD) 71 (54) months). At the time of the
study their ages ranged from 16 months to 16.5 years (mean 123 (70) months).
HCM was defined by the presence of a hypertrophied, non-dilated left ventricle,
in the absence of underlying cardiac, systemic disease or syndromic
conditions. Four patients had a family history of HCM and two had a family
history of premature (less than 50 years) sudden cardiac death of a first
degree relative. At the time of the study, no patients were receiving
treatment.
Seven patients complained of moderate exertional
dyspnoea; no patient had a history of chest pain or
syncope. Standard 12 lead ECG showed that seven patients had abnormal repolarisation. On 24 hour monitoring, all patients were in
stable sinus rhythm, and no arrhythmia was recorded. Ten patients underwent
exercise testing and none had hypotension, arrhythmias or ischaemia
during exercise. Five patients underwent catheterisation
and none of them had myocardial bridge. Of the 17 patients studied, 5 have
since died suddenly, 80 (25) months after the HRV investigation; their age at
death ranged from 102 months to 165 months (mean 116 (50) months).
Eighteen healthy children (9 males, mean age 132 (30) months) referred to
our institution for evaluation of a history of palpitations were studied as
control group. There were no differences in age, sex distribution, and mean
heart rate between patients and controls.
All subjects underwent 24 hour Holter monitoring and analysis of HRV.
Time domain analysis included the following indices: mean duration of RR
intervals (RR, ms); standard deviation of all RR intervals (SD, ms); square
root of the mean squared differences of successive RR intervals (r-MSSD, ms);
percentage of differences between adjacent RR intervals > 50 ms (pNN50, %).
Frequency domain analysis allowed the identification of two major peaks: a
low frequency component (LF, 0.04–0.15 Hz) and a high frequency peak centred around the respiratory frequency
(HF, 0.15–0.4 Hz). The total power spectrum (0.01–0.4 Hz) and LF/HF ratio were
computed.
Differences between groups were tested as appropriate. The effect on
prognosis of age, sex, family history, New York Heart Association (NYHA)
functional class, echocardiographic parameters,
abnormalities of repolarisation on ECG, and HRV
indices, were tested by multivariate logistic regression analysis. The
Kaplan-Meier method was used to examine differences in survival rate according
to prognostic factors. Comparisons between groups were based on the log rank
test. All tests were two sided. A probability value of p < 0.05 was
considered significant.
RESULTS
The results are presented in table 1. There
were no differences in HRV indices according to family history, ECG
abnormalities, and NYHA class.
|
|
Heart rate variability indices |
In the period following HRV analyses, 5 of the 17 patients with HCM died
suddenly. There were no differences between patients who died and survivors,
according to age at the time of diagnosis and the study, family history, sex
distribution, NYHA class, mean heart rate, ECG abnormalities or echocardiographic indices. Patients who died suddenly were
found to have a lower LF/HF ratio than survivors (0.9 (0.2) v 2.5 (1.3),
p = 0.03). Compared to patients with an LF/HF ratio more than 1.2, those with
an LF/HF ratio less than 1.2 had a higher incidence of sudden death (80% v
10 %, p = 0.02)(figs 1 and 22
).
). The sensitivity
of this threshold was 80% and its specificity 90%. The positive predictive
value was 80%, and the negative predictive value 90%. In the Kaplan-Meier
survival curve patients with an LF/HF ratio less than 1.2 had a poorer
prognosis (1 year 83%; 5 years 42%; 10 years 42%; log rank test p = 0.03). This
effect of the LF/HF ratio on prognosis was independent of age, sex, NYHA class,
family history, and echocardiographic indices.
|
|
Frequency domain analysis in a patient who died
suddenly. |
|
|
Frequency domain analysis in a survivor. |
DISCUSSION
Main markers of increased risk of sudden death in patients with HCM are a
positive family history of sudden death and previous syncope.1,2 Arrhythmias and haemodynamic factors such as an abnormal blood response to
exercise, and myocardial bridging have been suggested as risk factors. However,
accurate identification of high risk children is difficult, and sudden cardiac
death often occurs in children with no symptoms or clinical risk factors, as
was the case in our population.
Previous studies in adult populations with various cardiac diseases have
shown that HRV, which gives information about cardiac autonomic nervous inputs,
could predict arrhythmic events and sudden death.3 However, analysis
of HRV in adults with HCM did not add to the predictive accuracy of
conventional risk stratification.3
In our paediatric population, we found an
important correlation between clinical evolution and alterations in HRV. In
fact, all our patients who died suddenly had a low LF/HF ratio, with a cut-off
value of 1.2. This finding is probably related to the fact that mechanisms of
sudden death are different between children and adults.
A recent study by Yetman and colleagues4 showed that
myocardial ischaemia and arrhythmias are probably
responsible for sudden death in these children. In adults with non-obstructive
HCM, exercise induced abnormal blood pressure response, positive family
history, and a history of syncope are strong
predictors of sudden death. These risk factors suggest that a haemodynamic mechanism could be related to sudden death in
adults. In patients surviving a myocardial infarction, reduced HRV is a strong
independent risk factor of sudden death related to arrhythmic events. Hypothesising that sudden death in children with HCM could
be related to arrhythmic events, it is probable that
HRV analysis could be predictive in children despite not being so in adults.
Finally, Shusterman and colleagues5 have pointed out
that changes in the dynamics of RR intervals, rather than the absolute values
of the indices, facilitate arrhythmogenesis. For this
reason, we think that the LF/HF ratio—an index of sympathovagal
balance—rather than the absolute value of single indices, is a more powerful
predictor.
Abbreviations
- LF/HF, low frequency/high frequency
- HCM, hypertrophic cardiomyopathy
- HRV, heart rate variability
- NYHA,
References
1. McKenna W, Deanfield J, Faruqui A, et al. Prognosis of hypertrophic
cardiomyopathy: role of age and clinical, electrocardiographic and hemodynamic
features. Am J Cardiol 1981;47:532–8.
[PubMed]
2. McKenna WJ, Francklin RCG, Nihoyannopoulos
P, et al. Arrhythmia
and prognosis in infants and children with hypertrophic
cardiomyopathy. J Am Coll Cardiol
1988;11:147–51. [PubMed]
3. Task Force of the European Society of Cardiology and the North American
Society of Pacing and Electrophysiology. Heart rate variability.
Standard and measurements, physiological interpretation and
clinical use. Circulation 1996;93:1043–65. [PubMed]
4. Yetman AJ, Hamilton RM,
5. Shusterman V, Aysin B, Weiss R, et al. Dynamics of low-frequency
RR-interval oscillations preceding spontaneous ventricular tachycardia. Am
Heart J 2000;139:126–33. [PubMed]
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