Heart Rate Variability and Sudden Infant Death Syndrome FRANCESCO PERTICONE, ROBERTO CERAVOLO, RAFFAELE MAIO, CARMELA COSCO, and PIER LUIGI MATTIOLI From the Department of Internal Medicine, Department of Medicina Sperimentale e Clinica Medical School at Catanzaro, University of Reggio Calabria, Italy
PERTICONE, F., ET AL.: Heart Rate Variability and Sudden Infant Death Syndrome. The sudden infant death syndrome (SIDS) is the most common cause of death in infancy. The pathophysiological mechanism leading to SIDS is still obscure. In the QT hypothesis, the mechanism must be a n arrhythmogenic sympathetic imbalance: the infants die suddenly of cardiac arrhythmia. Recently, it has been suggested that analysis of heart rate variability [HRV), expressed as standard deviation or variance analysis, can provide adequate information on sympathovagal interaction. We studied 150 newborns enrolled in a previous prospective electrocardiographic study to evaluate the predictive value of QT interval for SIDS. We analyzed the ECGs recorded with infants alert on the fourth day of life and after 2 months. For each ECG, the HRV was calculated using the first standard deviation of of RR intervals (ms) measured for 1 minute. The average RR interval was 441 & 71 ms at the fourth day and 420 & 39 ms at the second month. The QTc and HRV mean values were 396 -+ 23 and 23 t 12 ms at the fourth day, 412 & 19 and 15 ? 7 msec at the second month. Therefore, the SD values of heart rate were coriehted h i t h QTc in order to assess a possible relationship between the two variables. The correlafion coefficient and regression equation were: -0.639 and y = 423.67 - 2.18"X (P < 0.002)at the fourth day, -0.146 and y = 418.09 - 0.37*X(NS) at the second month. In conclusion, our data seems to confirm a delayed maturation or impaired fuctioning of the autonomic nervous system in the first weeks of life, reflecting a direct correlation with QT prolongation. (PACE, VoI. 13, December, Part I1 1990) sudden infant death syndrome, long QT syndrome, heart rate variability, nervous autonomic system
Introduction The sudden infant death syndrome (SIDS) is the most common cause of death in infancy after the neonatal period. The pathogenetic mechanism leading to SIDS is still Evidence from previous research work on SIDS has suggested that a defect in the cardiorespiratory control mechanisms may be a present problem in some SIDS cases. Among the proposed cardiac causes, the QT hypothesis suggests that the mechanism could be an arrhythmogenic sympathetic imbalance, such as the infants die suddenly from cardiac arrhyth-
Address for reprints: Francesco Perticone, M.D., F.A.C.N., Via N Lombardi, 9, 88100-Catanzaro, Italy.
2096
mia secondary to a failure in autonomic cardiorespiratory contr01.~-~ Disturbances in the autonomic control of the cardiovascular function can contribute significantly to cardiac mortality. In fact, increased sympathetic activity has been shown to reduce cardiac electrical stability predisposing the heart to ventricular fibrillation, whereas parasympathetic activation may protect against arrhythmia format i ~ n . ' . ~ 'Periodic fluctuations in the heart rate variability (HRV) have been used as noninvasive measures of cardiac autonomic tone. HRV has been shown to decrease in congestive heart failure," severe coronary artery disease," and diabetic n e ~ r o p a t h y . ' ~Recently, some authors reported that patients with the lowest HRV, as measured by the standard deviation (SD). of the RR
December 1990, Part I1
PACE, Vol. 13
HEART RATE VARIABILITY
interval, had the most risk of dying suddenly. These authors concluded that HRV might be correlated with increased sympathetic and decreased parasympathetic a ~ t i v i t y . ' ~ . ' ~ The aim of this study was to investigate a possible correlation between a low HRV and SIDS.
Materials and Methods Data, obtained from a previous prospective study on SIDS, which started in December 1985,8 consisted of conventional 12-lead ECG made on 150 full-term infants at 4 days and 2 months of life. The procedures and objectives of the study were explained to the parents and informed consent was obtained. The ECGs, recorded at a paper speed of 50 mmis (Siemens, Mingophon 3, Siemens-Elema, Solna, Sweden), were performed with infants alert from 1 1 : O O am to 12:30 pm. The bipolar standard leads, the unipolar extremity leads, and the unipolar precordial leads (V,-V,, V,-V,) were recorded simultaneously. At the same time, a cardiac rhythm strip was recorded at least 1 minute at paper speed of 25 mm/sec. QT intervals were measured by two different physicians according to conventional techniques and expressed as a QT index, QT,. Using whichever lead (I, 11, or 111) provides easily identifiable T wave segments, QTc values were obtained by dividing the QT interval by the square root of the immediately preceding RR interval. The end of the T wave was determined by placing a straight edge on the isoelectric line and another on the final slope of the T wave. QT, value in each infant represents the mean of six or more nonconsecutive measurements. The heart rate, expressed in milliseconds, represent the RR intervals mean value averaged during 1-minute ECG strip. In the same way, for each ECG the HRV as the SD of 1-minute means of sinus cycle lengths (RR interval) in milliseconds was calculated. Finally, each variable was correlated with the other two in order to assess a possible relationship. Statistical comparison was performed by Student's t-test for paired data. Pearson correlation coefficients between on other two variables (QTc
PACE, Vol. 13
Table 1. Electrocardiographic Data in 150 Healthy Infants
RR Interval fms)
4 days 2 months P
441 410
+ 71 + 39
QTc
396 412
,001
+ 23 + 19
.001
HR Variability (ms)
23 + 12 15 + 7 .001
and heart rate) and HRV were calculated. All data are reported as mean k 1 SD.
Results Electrocardiographic data are reported in Table I. The average RR interyals Gere 441 ? 71 ms on the fourth day and dkcreased to 410 ? 39 ms on the second month (P < 0.001). The QT index mean values were 396 5 23 on the fourth day and 412 ? 19 on the second month, respectively (P < 0.001). The HRV mean value was 23 2 1 2 ms on the fourth day of life and decreased to 15 ? 7 ms on the second month (P < 0.001). Four days after birth a negative significant correlation between HRV and QT index was found (r = - 0.639; P < 0.001). The regression equation and the confidence limits of this slope are: y = 423.679 - 1.186*X (P < 0.001) and -1.186 -+ 10.110(148)*.117(Fig. 1).Similarly, a positive significant correlation between HRV and RR interval was found (r = 0.409; P < 0.001). On the contrary, any significant correlation was present between QT index and RR interval. At the second month of life any significant correlation was found between HRV and QT index (r = - 0.146) (Fig. l),and between QT index and RR interval. Again a positive significant correlation between HRV and RR interval was found again (r = 0.290; P < 0.01). Eight infants (5.3%) at the fourth day and 11 infants (7.3%) at the second month of life with QT, prolongation (mean 5 2 SD) ,were identified.
December 1990, Part I1
2097
PERTICONE, ET AL.
-
4th day (n
-
2nd month (n
160)
r
y
.-
. . .. . ’ .. ..:. ...,:.:i,.
-.a9 423.87
-
1.18 * X
. ... -
.
#
.
.
I
. ... . . .. ,
. .
380
1601
.
I
y
:. ..i: ’’’..: ,
,. .... . .
--
-.146 418.09
- .37* X
..
300 340 0
I0
20
30
40
60
80
70
80
Electrocardiographic findings of this group are reported in Table 11.
Discussion Heart rate and HRV are the result of a complex interaction of the sympathetic and parasympathetic divisions of the autonomic nervous system. There are distinct developmental differences in mean heart rate and in mean HRV between groups of normal infants and infants at increased risk for SIDS. These differences may reflect delayed mat-
Table II. Electrocardiographic Data in Babies with QTc Prolongation (mean + 2SD) 4 Days (n = 8)
2 Months (n = 11)
RR (ms)
QTc
HRV (ms)
RR (ms)
QTc
HRV (ms)
471 478 400 378 498 423 484 399
44 1 450 473 456 460 460 439 442
10 6 8 10 16 8 35 8
355 375 392 315 468 43 1 404 372 418 422 402
456 454 464 450 450 446 462 455 445 450 465
5 14 11 9 14 26 9 9 8 25 17
2098
0
10
20
30
40
60
00
uration or impaired functioning of the autonomic nervous system. At first Harper et and subsequently Leistner et al.I7 have reported an increase of heart rate in near-miss SIDS and in siblings of SIDS victims, particularly during nonREM sleep. Why heart rate increases is not clear. Harper and co-workers‘6 attribute it to a decrease in vagal activity: it is possible (hat tke mechanisms of parasympathetic. control’are inadequately developed in the group at risk for SIDS. Leistner et al.17 disagrees and supports the hypothesis that the faster heart rate in the surviving SIDS infants may be the consequence of an increase in sympathetic activity, a decrease in parasympathetic activity, or a combination of both. Recently, data reported by Guilleminault,18 obtained on only six near-miss SIDS infants and six controls, confirmed this observation, but did not shed much new light on the mechanisms involved. The absence of adequate information on the cardiac rhythm present at the time of death represents a major limitation for understanding the mechanism of SIDS in general and for assessing the cardiac hypothesis in particular. At present, both theoretical considerations and the factual knowledge about SIDS were not opposed to the possibility of primary cardiac death being responsible for a number of SIDS cases. This evidence implies that in these cases sudden cardiac death could be prevented, if subgroups at high risk could be identified. The data in the literature indicate that during the first week of life a percentage of possible SIDS victims already have electrocardiographic abnormalities potentially useful for risk stratification. These abnormalities involve a pro-
December 1990, Part I1
PACE, Vol. 13
HEART RATE VARIABILITY
longation of the QT interval and a reduction of HRV, and both reflect abnormalities in the autonomic control of the heart. Prolongation of the QT interval may suggest an imbalance in cardiac sympathetic innervation resulting in inappropriate modulation of ventricular repolarization, while reduced HRV indicates an impairment in cardiac vagal efferent activity. Of relevance to SIDS is the fact that both these abnormalities have been shown to be associated with a markedly increased risk for sudden cardiac death in adults. Our data shown a negative significant correlation between HRV and QT index prolongation at the fourth day, and confirms the increase of heart rate at the second month. Interestingly we found also the evidence that the HRV mean value is longer at fourth day (23 & 12 ms) than at the
second month (15 k 7 ms), whereas a significant correlation with QT index is present only 4 days after birth. Probably, during the first weeks of life the control of heart rate depends not only on the interaction of the sympathetic and parasympathetic nervous system, but also on the different maturation of the both right and left cardiac sympathetic nerves. In fact, the cardiac right sympathetic division induces an increase in the heart rate, while the prevalence of the cardiac left sympathetic nerve is arrhythmogenic and induces a prolongation of QT interval. In conclusion, our data seems to confirm a delayed maturation or impaired functioning of the autonomic nervous system at the first weeks of life, reflecting a direct correlation with QT interval prolongation.
References 1. Bergman AB, Beckwith JB, Ray CG. Sudden Infant
2.
3.
4.
5.
6. 7.
8.
9.
10.
Death Syndrome. The Proceedings of the Second International Conference on Causes of Sudden Death in Infants. Seattle, University of Washington Press, 1970, p. 18. First Report of a Multicentred Prospective Study into Sudden Infant Death Syndrome. Identification of infants destined to die unexpectedly during infancy: Evaluation of predictive importance of prolonged apnoea and disorders of cardiac rhythm or conduction. Br Med J 1983; 286:1092. PJ Schwartz, DP Southall, M Valdes-Dapena (eds.): The Sudden Infant Death Syndrome. Cardiac and Respiratory Mechanisms and Interventions. Ann NY Acad Sci 1988, p. 53. Schwartz PJ. Cardiac sympathetic innervation and the sudden infant death syndrome. A possible pathogenetic link. Am J Med 1976; 60:167. Schwartz PJ, Montemerlo M, Facchini M, et al. The QT interval throughout the first 6 months of life: A prospective study. Circulation 1982; 66:496. Valdes-Dapena M. Are some crib deaths sudden cardiac deaths? J Am Coll Cardiol 1985; 5:113B. Schwartz PJ. The quest for the mechanisms of the sudden infant death syndrome: Doubts and progress. Circulation 1987; 75:677. Perticone F, Mattioli PL. Prolonged QT interval: A marker of sudden infant death syndrome (SIDS)? (abstract) Eur Heart J 1988; 9(Suppl. 1):13. Corr PB, Yamada KA, Witkowski FX. Mechanisms controlling cardiac autonomic function and their relationships to arrhythmogenesis. In Fozzard HA, Haber E, Jennings RB, et al. (eds.): The Heart and Cardiovascular System. New York, Raven Press Publishers, 1986, p. 1343. Billman GE, Hoskins RS. Time-series analysis of
PACE, Vol. 13
11.
12.
13. 14.
15.
16.
17.
18.
heart rate variability during submaximal exercise. Evidence for reduced cardiac vagal tone in animals susceptible to ventricular fibrillation. Circulation .\ 1989; 80:146. Saul JP, Arai Y, h r & r RD, et al. Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. Am J Cardiol 1988; 61:1291. Airaksinen K, Ikaheimo MJ, Linnaluoto MK, et al. Impaired vagal heart rate control in coronary artery disease. Br Heart J 1988; 58:592. Ewing DJ, Clarke BF. Diagnosis and management of diabetic autonomic neuropathy. Br Med J 1982; 285:916. Kleiger RE, Miller JP, Bigger JT Jr, et al. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987; 59:256. Martin GJ, Magid NM, Myers G, et al. Heart rate variability and sudden death secondary to coronary artery disease during ambulatory electrocardiographic monitoring. Am J Cardiol 1987; 6036. Harper RM, Leake B, Hoppenbronwers T, et al. Polygraphic studies of normal infants and infants at risk for the sudden infant death syndrome: Heart rate and variability as a function of state. Pediat Res 1978; 12:778. Leistner HL, Haddad GG, Epstein RA, et al. Heart rate and heart rate variability during sleep in aborted sudden infant death syndrome. J Pediat 1980; 97:51. Guilleminault C. SIDS, near-miss SIDS and cardiac arrhythmia. In PJ Schwartz, DP Southall, M Valdes-Dapena (eds.): The Sudden Infant Death Syndrome. Cardiac and Respiratory Mechanisms and Interventions. Ann NY Acad Sci, 1988, p. 358.
December 1990, Part I1
2099
PERTICONE, F., ET AL.: Heart Rate Variability and Sudden Infant Death Syndrome. The sudden infant death syndrome (SIDS) is the most common cause of death in infancy. The pathophysiological mechanism leading to SIDS is still obscure. In the QT hypothesis, the mechanism must be a n arrhythmogenic sympathetic imbalance: the infants die suddenly of cardiac arrhythmia. Recently, it has been suggested that analysis of heart rate variability [HRV), expressed as standard deviation or variance analysis, can provide adequate information on sympathovagal interaction. We studied 150 newborns enrolled in a previous prospective electrocardiographic study to evaluate the predictive value of QT interval for SIDS. We analyzed the ECGs recorded with infants alert on the fourth day of life and after 2 months. For each ECG, the HRV was calculated using the first standard deviation of of RR intervals (ms) measured for 1 minute. The average RR interval was 441 & 71 ms at the fourth day and 420 & 39 ms at the second month. The QTc and HRV mean values were 396 -+ 23 and 23 t 12 ms at the fourth day, 412 & 19 and 15 ? 7 msec at the second month. Therefore, the SD values of heart rate were coriehted h i t h QTc in order to assess a possible relationship between the two variables. The correlafion coefficient and regression equation were: -0.639 and y = 423.67 - 2.18"X (P < 0.002)at the fourth day, -0.146 and y = 418.09 - 0.37*X(NS) at the second month. In conclusion, our data seems to confirm a delayed maturation or impaired fuctioning of the autonomic nervous system in the first weeks of life, reflecting a direct correlation with QT prolongation. (PACE, VoI. 13, December, Part I1 1990) sudden infant death syndrome, long QT syndrome, heart rate variability, nervous autonomic system
Introduction The sudden infant death syndrome (SIDS) is the most common cause of death in infancy after the neonatal period. The pathogenetic mechanism leading to SIDS is still Evidence from previous research work on SIDS has suggested that a defect in the cardiorespiratory control mechanisms may be a present problem in some SIDS cases. Among the proposed cardiac causes, the QT hypothesis suggests that the mechanism could be an arrhythmogenic sympathetic imbalance, such as the infants die suddenly from cardiac arrhyth-
Address for reprints: Francesco Perticone, M.D., F.A.C.N., Via N Lombardi, 9, 88100-Catanzaro, Italy.
2096
mia secondary to a failure in autonomic cardiorespiratory contr01.~-~ Disturbances in the autonomic control of the cardiovascular function can contribute significantly to cardiac mortality. In fact, increased sympathetic activity has been shown to reduce cardiac electrical stability predisposing the heart to ventricular fibrillation, whereas parasympathetic activation may protect against arrhythmia format i ~ n . ' . ~ 'Periodic fluctuations in the heart rate variability (HRV) have been used as noninvasive measures of cardiac autonomic tone. HRV has been shown to decrease in congestive heart failure," severe coronary artery disease," and diabetic n e ~ r o p a t h y . ' ~Recently, some authors reported that patients with the lowest HRV, as measured by the standard deviation (SD). of the RR
December 1990, Part I1
PACE, Vol. 13
HEART RATE VARIABILITY
interval, had the most risk of dying suddenly. These authors concluded that HRV might be correlated with increased sympathetic and decreased parasympathetic a ~ t i v i t y . ' ~ . ' ~ The aim of this study was to investigate a possible correlation between a low HRV and SIDS.
Materials and Methods Data, obtained from a previous prospective study on SIDS, which started in December 1985,8 consisted of conventional 12-lead ECG made on 150 full-term infants at 4 days and 2 months of life. The procedures and objectives of the study were explained to the parents and informed consent was obtained. The ECGs, recorded at a paper speed of 50 mmis (Siemens, Mingophon 3, Siemens-Elema, Solna, Sweden), were performed with infants alert from 1 1 : O O am to 12:30 pm. The bipolar standard leads, the unipolar extremity leads, and the unipolar precordial leads (V,-V,, V,-V,) were recorded simultaneously. At the same time, a cardiac rhythm strip was recorded at least 1 minute at paper speed of 25 mm/sec. QT intervals were measured by two different physicians according to conventional techniques and expressed as a QT index, QT,. Using whichever lead (I, 11, or 111) provides easily identifiable T wave segments, QTc values were obtained by dividing the QT interval by the square root of the immediately preceding RR interval. The end of the T wave was determined by placing a straight edge on the isoelectric line and another on the final slope of the T wave. QT, value in each infant represents the mean of six or more nonconsecutive measurements. The heart rate, expressed in milliseconds, represent the RR intervals mean value averaged during 1-minute ECG strip. In the same way, for each ECG the HRV as the SD of 1-minute means of sinus cycle lengths (RR interval) in milliseconds was calculated. Finally, each variable was correlated with the other two in order to assess a possible relationship. Statistical comparison was performed by Student's t-test for paired data. Pearson correlation coefficients between on other two variables (QTc
PACE, Vol. 13
Table 1. Electrocardiographic Data in 150 Healthy Infants
RR Interval fms)
4 days 2 months P
441 410
+ 71 + 39
QTc
396 412
,001
+ 23 + 19
.001
HR Variability (ms)
23 + 12 15 + 7 .001
and heart rate) and HRV were calculated. All data are reported as mean k 1 SD.
Results Electrocardiographic data are reported in Table I. The average RR interyals Gere 441 ? 71 ms on the fourth day and dkcreased to 410 ? 39 ms on the second month (P < 0.001). The QT index mean values were 396 5 23 on the fourth day and 412 ? 19 on the second month, respectively (P < 0.001). The HRV mean value was 23 2 1 2 ms on the fourth day of life and decreased to 15 ? 7 ms on the second month (P < 0.001). Four days after birth a negative significant correlation between HRV and QT index was found (r = - 0.639; P < 0.001). The regression equation and the confidence limits of this slope are: y = 423.679 - 1.186*X (P < 0.001) and -1.186 -+ 10.110(148)*.117(Fig. 1).Similarly, a positive significant correlation between HRV and RR interval was found (r = 0.409; P < 0.001). On the contrary, any significant correlation was present between QT index and RR interval. At the second month of life any significant correlation was found between HRV and QT index (r = - 0.146) (Fig. l),and between QT index and RR interval. Again a positive significant correlation between HRV and RR interval was found again (r = 0.290; P < 0.01). Eight infants (5.3%) at the fourth day and 11 infants (7.3%) at the second month of life with QT, prolongation (mean 5 2 SD) ,were identified.
December 1990, Part I1
2097
PERTICONE, ET AL.
-
4th day (n
-
2nd month (n
160)
r
y
.-
. . .. . ’ .. ..:. ...,:.:i,.
-.a9 423.87
-
1.18 * X
. ... -
.
#
.
.
I
. ... . . .. ,
. .
380
1601
.
I
y
:. ..i: ’’’..: ,
,. .... . .
--
-.146 418.09
- .37* X
..
300 340 0
I0
20
30
40
60
80
70
80
Electrocardiographic findings of this group are reported in Table 11.
Discussion Heart rate and HRV are the result of a complex interaction of the sympathetic and parasympathetic divisions of the autonomic nervous system. There are distinct developmental differences in mean heart rate and in mean HRV between groups of normal infants and infants at increased risk for SIDS. These differences may reflect delayed mat-
Table II. Electrocardiographic Data in Babies with QTc Prolongation (mean + 2SD) 4 Days (n = 8)
2 Months (n = 11)
RR (ms)
QTc
HRV (ms)
RR (ms)
QTc
HRV (ms)
471 478 400 378 498 423 484 399
44 1 450 473 456 460 460 439 442
10 6 8 10 16 8 35 8
355 375 392 315 468 43 1 404 372 418 422 402
456 454 464 450 450 446 462 455 445 450 465
5 14 11 9 14 26 9 9 8 25 17
2098
0
10
20
30
40
60
00
uration or impaired functioning of the autonomic nervous system. At first Harper et and subsequently Leistner et al.I7 have reported an increase of heart rate in near-miss SIDS and in siblings of SIDS victims, particularly during nonREM sleep. Why heart rate increases is not clear. Harper and co-workers‘6 attribute it to a decrease in vagal activity: it is possible (hat tke mechanisms of parasympathetic. control’are inadequately developed in the group at risk for SIDS. Leistner et al.17 disagrees and supports the hypothesis that the faster heart rate in the surviving SIDS infants may be the consequence of an increase in sympathetic activity, a decrease in parasympathetic activity, or a combination of both. Recently, data reported by Guilleminault,18 obtained on only six near-miss SIDS infants and six controls, confirmed this observation, but did not shed much new light on the mechanisms involved. The absence of adequate information on the cardiac rhythm present at the time of death represents a major limitation for understanding the mechanism of SIDS in general and for assessing the cardiac hypothesis in particular. At present, both theoretical considerations and the factual knowledge about SIDS were not opposed to the possibility of primary cardiac death being responsible for a number of SIDS cases. This evidence implies that in these cases sudden cardiac death could be prevented, if subgroups at high risk could be identified. The data in the literature indicate that during the first week of life a percentage of possible SIDS victims already have electrocardiographic abnormalities potentially useful for risk stratification. These abnormalities involve a pro-
December 1990, Part I1
PACE, Vol. 13
HEART RATE VARIABILITY
longation of the QT interval and a reduction of HRV, and both reflect abnormalities in the autonomic control of the heart. Prolongation of the QT interval may suggest an imbalance in cardiac sympathetic innervation resulting in inappropriate modulation of ventricular repolarization, while reduced HRV indicates an impairment in cardiac vagal efferent activity. Of relevance to SIDS is the fact that both these abnormalities have been shown to be associated with a markedly increased risk for sudden cardiac death in adults. Our data shown a negative significant correlation between HRV and QT index prolongation at the fourth day, and confirms the increase of heart rate at the second month. Interestingly we found also the evidence that the HRV mean value is longer at fourth day (23 & 12 ms) than at the
second month (15 k 7 ms), whereas a significant correlation with QT index is present only 4 days after birth. Probably, during the first weeks of life the control of heart rate depends not only on the interaction of the sympathetic and parasympathetic nervous system, but also on the different maturation of the both right and left cardiac sympathetic nerves. In fact, the cardiac right sympathetic division induces an increase in the heart rate, while the prevalence of the cardiac left sympathetic nerve is arrhythmogenic and induces a prolongation of QT interval. In conclusion, our data seems to confirm a delayed maturation or impaired functioning of the autonomic nervous system at the first weeks of life, reflecting a direct correlation with QT interval prolongation.
References 1. Bergman AB, Beckwith JB, Ray CG. Sudden Infant
2.
3.
4.
5.
6. 7.
8.
9.
10.
Death Syndrome. The Proceedings of the Second International Conference on Causes of Sudden Death in Infants. Seattle, University of Washington Press, 1970, p. 18. First Report of a Multicentred Prospective Study into Sudden Infant Death Syndrome. Identification of infants destined to die unexpectedly during infancy: Evaluation of predictive importance of prolonged apnoea and disorders of cardiac rhythm or conduction. Br Med J 1983; 286:1092. PJ Schwartz, DP Southall, M Valdes-Dapena (eds.): The Sudden Infant Death Syndrome. Cardiac and Respiratory Mechanisms and Interventions. Ann NY Acad Sci 1988, p. 53. Schwartz PJ. Cardiac sympathetic innervation and the sudden infant death syndrome. A possible pathogenetic link. Am J Med 1976; 60:167. Schwartz PJ, Montemerlo M, Facchini M, et al. The QT interval throughout the first 6 months of life: A prospective study. Circulation 1982; 66:496. Valdes-Dapena M. Are some crib deaths sudden cardiac deaths? J Am Coll Cardiol 1985; 5:113B. Schwartz PJ. The quest for the mechanisms of the sudden infant death syndrome: Doubts and progress. Circulation 1987; 75:677. Perticone F, Mattioli PL. Prolonged QT interval: A marker of sudden infant death syndrome (SIDS)? (abstract) Eur Heart J 1988; 9(Suppl. 1):13. Corr PB, Yamada KA, Witkowski FX. Mechanisms controlling cardiac autonomic function and their relationships to arrhythmogenesis. In Fozzard HA, Haber E, Jennings RB, et al. (eds.): The Heart and Cardiovascular System. New York, Raven Press Publishers, 1986, p. 1343. Billman GE, Hoskins RS. Time-series analysis of
PACE, Vol. 13
11.
12.
13. 14.
15.
16.
17.
18.
heart rate variability during submaximal exercise. Evidence for reduced cardiac vagal tone in animals susceptible to ventricular fibrillation. Circulation .\ 1989; 80:146. Saul JP, Arai Y, h r & r RD, et al. Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. Am J Cardiol 1988; 61:1291. Airaksinen K, Ikaheimo MJ, Linnaluoto MK, et al. Impaired vagal heart rate control in coronary artery disease. Br Heart J 1988; 58:592. Ewing DJ, Clarke BF. Diagnosis and management of diabetic autonomic neuropathy. Br Med J 1982; 285:916. Kleiger RE, Miller JP, Bigger JT Jr, et al. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987; 59:256. Martin GJ, Magid NM, Myers G, et al. Heart rate variability and sudden death secondary to coronary artery disease during ambulatory electrocardiographic monitoring. Am J Cardiol 1987; 6036. Harper RM, Leake B, Hoppenbronwers T, et al. Polygraphic studies of normal infants and infants at risk for the sudden infant death syndrome: Heart rate and variability as a function of state. Pediat Res 1978; 12:778. Leistner HL, Haddad GG, Epstein RA, et al. Heart rate and heart rate variability during sleep in aborted sudden infant death syndrome. J Pediat 1980; 97:51. Guilleminault C. SIDS, near-miss SIDS and cardiac arrhythmia. In PJ Schwartz, DP Southall, M Valdes-Dapena (eds.): The Sudden Infant Death Syndrome. Cardiac and Respiratory Mechanisms and Interventions. Ann NY Acad Sci, 1988, p. 358.
December 1990, Part I1
2099
