QT INTERVAL IN SIDS/Kelly, Shannon, Liberthson Shape #3 If A2r, B2J, and the turbulent portion of the signal is of relatively low frequency, i.e., T2-T1, the autocorrelation appears as in figure 2b. If the two time scales are not readily apparent, as in figure 2b, T0 is the correct turbulent scale and the function's width is determined on the axis at point P. The pattern in figure 2b is differentiated from that of figure lb, which has no information about constriction, because figure 2b displays a sharp, triangular peak with straight sides. Figure 2b is observed in tortuous arteries with minimal occlusion and was produced by the kinked artery previously illustrated in text (fig. 5).
References
Additional cases when turbulence and pulse wave amplitudes are the same order of magnitude are shown in figures 2c and 2d. In both cases, T2 must be differentiated from TO and determined at the point P where the autocorrelation curvature is at a maximum.
Shape #6
2.
3. 4.
6. 7. 8.
Finally, if the turbulence is minimal and hence A2r,>> B2T,, there is no flow information available. In this case T. merely reflects the properties of the pulse wave and the data must be discarded. This case would appear as in figure lb. It is evident from the above that if a bruit is sufficiently turbulent, the autocorrelation can be interpreted correctly to yield the appropriate turbulent time scale. Visual observation of the oscilloscope signal trace is necessary initially in deciding whether there is excessive ambient noise in the signal. Ambient noise is not distinguished from turbulence in the autocorrelation, but is readily distinguished in oscilloscope form. When ambient noise is excessive, especially if the turbulent signal is of very low amplitude, the data must be discarded (see fig. 2, text).
new noninvasive diagnostic method for studying arterial disease. Proc Nat Acad Sciences 67: 935, 1970 Duncan GW, Gruber JO, Dewey CF Jr, Myers GS, Lees RS: Evaluation of carotid stenosis by phonoangiography. N Engl J Med 293: 1124, 1975 Lighthill J: Mathematical biofluiddynamics. Philadelphia, Society for Industrial and Applied Mathematics, 1975, p 227-252 Porje IG, Rudewald B: Hemodynamic studies with differential pressure technique. Acta Physiol Scandinav 51: 116, 1961 Barnett GO, Greenfield JC Jr, Fox SM: The technique of estimating the instantaneous aortic blood velocities in man from the pressure gradient. Am Heart J 62: 359, 1961 Dewey CF Jr, Metzinger RF, Klitzner TS, Holford SK: Analysis and interpretation of arterial sounds using a small clinical computer system. Proceedings of the San Diego Biomedical Symposium 12: 119, 1973 Fredberg JJ: Pseudo-sound generation at atherosclerotic constrictions in arteries. Bull Math Biol 36: 143, 1974 Tennekes H, Lumsley JL: A First Course in Turbulence. Cambridge, MIT Press, 1972, pp 262-273 Wiener N: Generalized harmonic analysis. Acta Math 55: 117, 1930 Bradshaw P: An introduction to turbulence and its measurement. Oxford, Pergamon Press, 1971, pp 33-34 Coran AG, Warren R: Arteriographic changes in femoropopliteal arteriosclerosis obliterans. A five-year follow-up study. N Engl J Med 274: 643, 1966 Chilvers AS, Thomas ML, Browse NL: The progression of arteriosclerosis. A radiologic study. Circulation 50: 401, 1974 Barndt R Jr, Blankenhorn DH, Crawford DW, Brooks SH: Regression and progression of early femoral atherosclerosis in treated hyperlipoproteinemic patients. Ann Intern Med. February 1976
1. Lees RS, Dewey CF Jr: Phonoangiography. A
5.
Shapes #4 and #5
633
9. 10.
11.
12. 13.
The Role of the QT Interval in the Sudden Infant Death Syndrome DOROTHY H. KELLY, M.D., DANIEL C. SHANNON, M.D., AND RICHARD R. LIBERTHSON, M.D. SUMMARY To evaluate the role of QT interval prolongation in the genesis of the sudden infant death syndrome (SIDS), the postresuscitation electrocardiograms of 21 aborted SIDS infants were reviewed. The infants had been found apneic, cyanotic, limp and unresponsive during sleep and required vigorous physical stimulation and mouth-to-mouth resuscitation. Three subsequently experienced repeat similar episodes from which they could not be resuscitated.
Extensive studies eliminated all "known" etiologies for death. The QT intervals of these infants were compared to age and sex matched normal infants as well as to established normal values in the literature; in both the aborted and the subsequent actual SIDS infants, the QT intervals were not significantly different from those of the normal population. Thus, we conclude that QT interval prolongation does not play a major role in the genesis of the aborted SIDS.
THE SUDDEN INFANT DEATH SYNDROME (SIDS) is the leading cause of infant death between the ages of I and 12 months, and claims approximately 10,000 lives in the United States each year.` Because these deaths are sudden, usually occur outside of the hospital, are observed only rarely by physicians, and have few associated autopsy findings,4'5 we still know very little about their etiology. Explanations for these deaths include asphyxia, laryngeal or bronchospasm, infection, occult endocrine, neurologic or renal disease, apnea, and autonomic dysfunction.6"' In addi-
tion, QT interval prolongation with fatal ventricular arrhythmia has been proposed as a cause for SIDS.'2 17 However, because SIDS victims themselves rarely have electrocardiographic evaluation before death, recent workers have examined relatives of SIDS infants because it is known that QT prolongation in some families is genetically transmitted.18-20 Based on this indirect approach, these studies suggest a causal relationship between QT prolongation and the SIDS.21 22 In this report, we examine the postresuscitation QT intervals of aborted SIDS infants, including three who subsequently died from actual SIDS.
From the Departments of Pediatrics and Medicine (Cardiac Unit), Massachusetts General Hospital and Harvard Medical School, Boston, Methods Massachusetts. Address for reprints: Richard R. Liberthson, M.D., Cardiac Unit, Between 1974 and 1976, 21 survivors of the aborted SIDS Massachusetts General Hospital, Boston, Massachusetts 02114. were referred to the Massachusetts General Hospital Received November 1, 1976; revision accepted November 29, 1976. Downloaded from http://circ.ahajournals.org/ at BATH UNIV on June 27, 2015
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(MGH) for evaluation and treatment. These infants were found apneic, cyanotic, limp, and unresponsive during sleep, and required vigorous physical stimulation and mouth-tomouth resuscitation. No infant required electrical defibrillation. All infants had complete history and physical examination as well as laboratory evaluation including complete blood count, urinalysis, measurement of serum calcium, phosphate, magnesium, glucose, and amino acids, evaluation of urinary amino acids, chest and skull radiography, electroencephalograms, and continuous twelve-hour pneumogram recordings to evaluate respirations and heart rate.25 All known causes of sudden death24 were ruled out. The 21 aborted SIDS infants included three infants who subsequently experienced similar episodes from which they could not be resuscitated. These three became actual SIDS babies. At autopsy, no cause of death was found in them. In six of the 21 aborted SIDS infants, the aborted episode was so severe that transient hypoxic damage following resuscitation was present, and 10 resuscitated infants had subsequent prolonged monitored apneic episodes lasting longer than 20 seconds which required bag and mask resuscitation and vigorous physical stimulation. Forty-six normal control infants matched for sex and age were selected from our ambulatory clinic population, and normal values for the QT interval were selected from the literature.25 25 All infants had standard 12 lead electrocardiograms taken within 48 hours of the aborted SIDS episode. These electrocardiograms were recorded while the infants were resting quietly using Marquette series 2,000 electrocardiographic recorders at 25 mm/sec paper speed. QT intervals were determined by averaging six complexes in lead II. Care was taken to avoid including U or P waves, and the QT intervals were measured from the onset of the Q wave (or the R wave if no Q wave was present) to the end of the T wave (junction with the isoelectric baseline). Only complexes with normal QRS and T waves were evaluated and no patient was taking medication which is known to alter the QT interval at the time of recording. Heart rate was calculated from the same complexes in which QT intervals were measured by averaging six R-R intervals in lead II. All QT intervals were corrected for heart rate (QTc) by dividing the QT by the square root of the R-R interval.27 Measurements were made on four separate occasions by two observers without knowledge of whether the patient was an aborted SIDS or a normal control. The QTc intervals of the aborted patients were plotted on the nomogram of QTc intervals derived by Alimurung et al.26 Results The general characteristics of these infants are shown in table 1. Physical and neurologic examinations were normal except in the six patients with transient postresuscitation
VOL 55, No 4, APRIL 1977
hypoxia, and laboratory data and chest and skull radiographs were also normal. The mean serum calcium level was 9.9 mm/100 ml (range 9.0 to 10.9). Electroencephalograms were normal except in two of the infants who had transient hypoxic changes. Pneumogram recordings in ten infants demonstrated episodes of prolonged sleep apnea (greater than 20 seconds). The QT intervals in aborted SIDS ranged from 0.20 to 0.33 seconds with a mean of 0.26 seconds compared to our normal infants in whom QT intervals ranged from 0.20 to 0.31 seconds with a mean of 0.25 seconds. The QTc for the aborted SIDS ranged from 0.35 to 0.42 seconds with a mean of 0.39 seconds compared to the QTc for normal controls which ranged from 0.34 to 0.43 seconds with a mean of 0.39 seconds. The QT intervals of our three infants who subsequently died from actual SIDS were 0.27, 0.28 and 0.28 and their calculated mean QTc was 0.39 seconds. Reports in the literature of 861 normal infants reveal a mean QTc of 0.39 seconds. The differences among the QTc in the aborted SIDS patients, the actual SIDS, our normal control infants, and reported normals in the literature25 26 were not statistically significant; and the QTc intervals in the aborted and actual patients were within the normal range when plotted on Alimurung's nomogram.2' To rule out possible age related QT variations, we compared our study and control populations by age as shown in table 2 and did not find significant differences in QTc intervals between these groups.
Discussion
While the etiology for SIDS is still unclear, review of our infants with aborted SIDS as well as three infants who subsequently were actual SIDS, reveals that QT interval prolongation is not present in these infants following resuscitation. Thus, unlike previous reports21' 22 which demonstrated QT prolongation in relatives of SIDS and thus suggested that QT prolongation is related to SIDS, we could not demonstrate QT prolongation in the aborted or actual SIDS infants themselves. In addition, as shown in table 2, we could find no age subgroup in which the QTc intervals differed from controls. Further strong evidence against involvement of QT prolongation in SIDS derives from the fact that the presumed mechanism for death in QT prolongation is ventricular fibrillation28 which in nearly all patients requires defibrillation; in none of our resuscitations was defibrillation needed. It has been suggested that QT prolongation may be related to sleep or activity,29-3' and it is therefore possible that our single ECG samples did not detect intermittent QT prolongation; however, evaluation of this requires continuous long-term ECG recordings. While it is conceivable that aborted SIDS is not the same
TABLE 1. Characterization of Aborted SIDS and Normal Control Infants Mean age
Mean weight (kg)
Sex M/F
Mean gestational age (weeks)
Mean birth weight
(kg) 21 Aborted SIDS 4.6 6.2 13/8 39 2.9 3 10.0* Subsequent actual SIDS 8.2 2/1 40 3.2 Normal control infants MGH 46 6.2 4.5 25/21 40 3.2 Normal controls literature25' 26 861 5.5 409/449 *Ages at the initial aborted SIDS episodes were 1, 3, and 7 months and at the actual SIDS episodes were 10, 8 and 12 months. No.
(months)
Downloaded from http://circ.ahajournals.org/ at BATH UNIV on June 27, 2015
635
QT INTERVAL IN SIDS/Kelly, Shannon, Liberthson TABLE 2. QTc Intervals in Aborted SIDS and Normal Control Infants by Age Age
No.
1 mo 2 mos 3 mos 4-6 mos 7-9 mos 10 + mos Total
5 6 2 3 2 3 21
Aborted SIDS QTc Range
.39 .40 .39 .40 .38 .38
.39
.35-42 .38-.42 .38.40
.39-.40 .36.40 .35-.42 .35-.42
Normal control infants (MGH) No. QTc Range
13 10 2 10 3 8
46
entity as actual SIDS and therefore that our study infants are not representative of the actual SIDS population, we believe this is not so because three of our study infants subsequently died of actual SIDS, six had significant clinical hypoxia demonstrating the severity of their aborted episodes, and ten infants had pneumogram documentation of prolonged, severe, and clinically significant apnea, which we believe could have precipitated actual SIDS. We conclude from our data that demonstrable QT prolongation is not present in resuscitated aborted SIDS, and therefore is unlikely to be a major cause for the sudden infant death syndrome.
Acknowledgment The authors wish to thank Kathleen O'Connell and Margaret Paolini for their assistance in the preparation of this study.
References 1. Bergman AB, Ray CG, Pomeroy MA, Wahl PW, Beckwith JB: Studies of the sudden infant death syndrome in King County, Washington, Ill. Epidemiology. Pediatrics 49: 860, 1972 2. Valdes-Dapena MA: Sudden, unexpected and unexplained death in infancy. A status report - 1973. N Engl J Med 289: 1195, 1973 3. Sudden Infant Death Syndrome: Proceedings of the Second International Conference on Causes of Sudden Death in Infants, edited by Bergman AB, Beckwith JB, Ray CG. Seattle, University of Washington Press, 1970 4. Naeye RL: Hypoxemia and the sudden infant death syndrome. Science 186: 837, 1974 5. Naeye RL: Pulmonary arterial abnormalities in the sudden-infant-death syndrome. N Engl J Med 289: 1167, 1973 6. Valdes-Dapena MA: Sudden and unexpected death in infancy: A review of the world literature. Pediatrics 39: 123, 1967 7. Marx JL: Crib death: Some promising leads but no solution yet. Science 189: 367, 1975 8. Steinschneider A: Prolonged apnea and the sudden infant death syndrome: Clinical and laboratory observations. Pediatrics 50: 646, 1972 9. James TN: Sudden death of babies. Circulation 53: 1, 1976 10. Downing S, Lee JC: Laryngeal chemosensitivity: A possible mechanism for sudden infant death syndrome. Pediatrics 55: 640, 1975
.39 .38 .40 .39 .38 .39 .39
.34,.43 .34-.42 .39-.40 .36,43
.35-.40 .35-.42 .34-.43
Normal controls literature's5 26 QTc No. Range
107 98 94 184 103 107 693
.39 .40 .40 .40 .40 .39 .40
.32-.46 .34-.47 .34-.47 .33-.49
.32-.45 .32-.45 .32-.49
11. Urquhart GED, Grist NR: Virological studies of sudden, unexplained infant deaths in Glascow 1967-70. J Clin Pathol 25: 443, 1972 12. Jervell A, Lange-Nielsen F: Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death. Am Heart J 57: 59, 1957 13. Ward OC: A new familial cardiac syndrome in children. J Irish Med Assoc 54: 103, 1964 14. Romano C: Congenital cardiac arrhythmia. Lancet 1: 658, 1965 15. James TN: QT prolongation and sudden death. Mod Concepts Cardiovasc Dis 38: 35, 1969 16. Reynolds EW, Vander Ark CR: Quinidine syncope and the delayed repolarization syndromes. Mod Concepts Cardiovasc Dis 45: 117, 1976 17. Schwartz PJ, Periti M, Malliani A: The long Q-T syndrome. Am Heart J 89: 378, 1975 18. Fraser GR, Froggatt P, James TN: Congenital deafness associated with electrocardiographic abnormalities, fainting attacks and sudden death. A recessive syndrome. Quart J Med (New Series) 33: 361, 1964 19. Fraser GR, Froggatt P, Murphy T: Genetical aspects of the cardioauditory syndrome of Jervell and Lange-Nielsen (congenital deafness and electrocardiographic abnormalities). Ann Hum Genet (London) 28: 133, 1964 20. Garza LA, Vick RL, Nora JJ, McNamara DG: Heritable Q-T prolongation without deafness. Circulation 41: 30, 1970 21. Aaron BJ, Goldstein RE, Clarck CE, Fisher RS, Epstein SE: Potential role of QT interval prolongation in sudden infant death syndrome. Circulation 54: 423, 1976 22. Schwartz PJ: Cardiac sympathetic innervation and the sudden infant death syndrome. A possible pathogenetic link. Am J Med 60: 167, 1976 23. Stein IM, Shannon DC: The pediatric pneumogram. Pediatrics 55: 599, 1975 24. Bernstein J: Sudden and unexpected death. In Pediatrics, edited by Barnett HL. New York, Appleton-Century-Crofts, 1972, pp 575-578 25. McCammon RW: A longitudinal study of electrocardiographic intervals in healthy children. Acta Paediatr Scand (Uppsala) (suppl) 126, 1961 26. Alimurung MM, Joseph LG, Craige E, Massell BF: The QT interval in normal infants and children. Circulation 1: 1329, 1950 27. Bazett HC: An analysis of the time-relations of electrocardiograms. Heart 7: 353, 1920 28. Smirk FH, Palmer DG: A myocardial syndrome: With particular reference to occurrence of sudden death and of premature systoles interrupting antecedent T waves. Am J Cardiol 6: 620, 1960 29. Phillips J, Ichinose H: Clinical and pathologic studies in the hereditary syndrome of a long Q-T interval, syncopal spells and sudden death. Chest 58: 236, 1970 30. Levine SA, Woodworth CR: Congenital deaf-mutism, prolonged Q-T interval, syncopal attacks, and sudden death. N Engl J Med 259: 412, 1958 31. Ferrer PL, Talner NS: Changes in the QT index with sleep in young mammals. (abstr) Pediatr Res 8: 75, 1974
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The role of the QT interval in the sudden infant death syndrome. D H Kelly, D C Shannon and R R Liberthson Circulation. 1977;55:633-635 doi: 10.1161/01.CIR.55.4.633 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1977 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/55/4/633
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Downloaded from http://circ.ahajournals.org/ at BATH UNIV on June 27, 2015
References
Additional cases when turbulence and pulse wave amplitudes are the same order of magnitude are shown in figures 2c and 2d. In both cases, T2 must be differentiated from TO and determined at the point P where the autocorrelation curvature is at a maximum.
Shape #6
2.
3. 4.
6. 7. 8.
Finally, if the turbulence is minimal and hence A2r,>> B2T,, there is no flow information available. In this case T. merely reflects the properties of the pulse wave and the data must be discarded. This case would appear as in figure lb. It is evident from the above that if a bruit is sufficiently turbulent, the autocorrelation can be interpreted correctly to yield the appropriate turbulent time scale. Visual observation of the oscilloscope signal trace is necessary initially in deciding whether there is excessive ambient noise in the signal. Ambient noise is not distinguished from turbulence in the autocorrelation, but is readily distinguished in oscilloscope form. When ambient noise is excessive, especially if the turbulent signal is of very low amplitude, the data must be discarded (see fig. 2, text).
new noninvasive diagnostic method for studying arterial disease. Proc Nat Acad Sciences 67: 935, 1970 Duncan GW, Gruber JO, Dewey CF Jr, Myers GS, Lees RS: Evaluation of carotid stenosis by phonoangiography. N Engl J Med 293: 1124, 1975 Lighthill J: Mathematical biofluiddynamics. Philadelphia, Society for Industrial and Applied Mathematics, 1975, p 227-252 Porje IG, Rudewald B: Hemodynamic studies with differential pressure technique. Acta Physiol Scandinav 51: 116, 1961 Barnett GO, Greenfield JC Jr, Fox SM: The technique of estimating the instantaneous aortic blood velocities in man from the pressure gradient. Am Heart J 62: 359, 1961 Dewey CF Jr, Metzinger RF, Klitzner TS, Holford SK: Analysis and interpretation of arterial sounds using a small clinical computer system. Proceedings of the San Diego Biomedical Symposium 12: 119, 1973 Fredberg JJ: Pseudo-sound generation at atherosclerotic constrictions in arteries. Bull Math Biol 36: 143, 1974 Tennekes H, Lumsley JL: A First Course in Turbulence. Cambridge, MIT Press, 1972, pp 262-273 Wiener N: Generalized harmonic analysis. Acta Math 55: 117, 1930 Bradshaw P: An introduction to turbulence and its measurement. Oxford, Pergamon Press, 1971, pp 33-34 Coran AG, Warren R: Arteriographic changes in femoropopliteal arteriosclerosis obliterans. A five-year follow-up study. N Engl J Med 274: 643, 1966 Chilvers AS, Thomas ML, Browse NL: The progression of arteriosclerosis. A radiologic study. Circulation 50: 401, 1974 Barndt R Jr, Blankenhorn DH, Crawford DW, Brooks SH: Regression and progression of early femoral atherosclerosis in treated hyperlipoproteinemic patients. Ann Intern Med. February 1976
1. Lees RS, Dewey CF Jr: Phonoangiography. A
5.
Shapes #4 and #5
633
9. 10.
11.
12. 13.
The Role of the QT Interval in the Sudden Infant Death Syndrome DOROTHY H. KELLY, M.D., DANIEL C. SHANNON, M.D., AND RICHARD R. LIBERTHSON, M.D. SUMMARY To evaluate the role of QT interval prolongation in the genesis of the sudden infant death syndrome (SIDS), the postresuscitation electrocardiograms of 21 aborted SIDS infants were reviewed. The infants had been found apneic, cyanotic, limp and unresponsive during sleep and required vigorous physical stimulation and mouth-to-mouth resuscitation. Three subsequently experienced repeat similar episodes from which they could not be resuscitated.
Extensive studies eliminated all "known" etiologies for death. The QT intervals of these infants were compared to age and sex matched normal infants as well as to established normal values in the literature; in both the aborted and the subsequent actual SIDS infants, the QT intervals were not significantly different from those of the normal population. Thus, we conclude that QT interval prolongation does not play a major role in the genesis of the aborted SIDS.
THE SUDDEN INFANT DEATH SYNDROME (SIDS) is the leading cause of infant death between the ages of I and 12 months, and claims approximately 10,000 lives in the United States each year.` Because these deaths are sudden, usually occur outside of the hospital, are observed only rarely by physicians, and have few associated autopsy findings,4'5 we still know very little about their etiology. Explanations for these deaths include asphyxia, laryngeal or bronchospasm, infection, occult endocrine, neurologic or renal disease, apnea, and autonomic dysfunction.6"' In addi-
tion, QT interval prolongation with fatal ventricular arrhythmia has been proposed as a cause for SIDS.'2 17 However, because SIDS victims themselves rarely have electrocardiographic evaluation before death, recent workers have examined relatives of SIDS infants because it is known that QT prolongation in some families is genetically transmitted.18-20 Based on this indirect approach, these studies suggest a causal relationship between QT prolongation and the SIDS.21 22 In this report, we examine the postresuscitation QT intervals of aborted SIDS infants, including three who subsequently died from actual SIDS.
From the Departments of Pediatrics and Medicine (Cardiac Unit), Massachusetts General Hospital and Harvard Medical School, Boston, Methods Massachusetts. Address for reprints: Richard R. Liberthson, M.D., Cardiac Unit, Between 1974 and 1976, 21 survivors of the aborted SIDS Massachusetts General Hospital, Boston, Massachusetts 02114. were referred to the Massachusetts General Hospital Received November 1, 1976; revision accepted November 29, 1976. Downloaded from http://circ.ahajournals.org/ at BATH UNIV on June 27, 2015
CIRCULATION
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(MGH) for evaluation and treatment. These infants were found apneic, cyanotic, limp, and unresponsive during sleep, and required vigorous physical stimulation and mouth-tomouth resuscitation. No infant required electrical defibrillation. All infants had complete history and physical examination as well as laboratory evaluation including complete blood count, urinalysis, measurement of serum calcium, phosphate, magnesium, glucose, and amino acids, evaluation of urinary amino acids, chest and skull radiography, electroencephalograms, and continuous twelve-hour pneumogram recordings to evaluate respirations and heart rate.25 All known causes of sudden death24 were ruled out. The 21 aborted SIDS infants included three infants who subsequently experienced similar episodes from which they could not be resuscitated. These three became actual SIDS babies. At autopsy, no cause of death was found in them. In six of the 21 aborted SIDS infants, the aborted episode was so severe that transient hypoxic damage following resuscitation was present, and 10 resuscitated infants had subsequent prolonged monitored apneic episodes lasting longer than 20 seconds which required bag and mask resuscitation and vigorous physical stimulation. Forty-six normal control infants matched for sex and age were selected from our ambulatory clinic population, and normal values for the QT interval were selected from the literature.25 25 All infants had standard 12 lead electrocardiograms taken within 48 hours of the aborted SIDS episode. These electrocardiograms were recorded while the infants were resting quietly using Marquette series 2,000 electrocardiographic recorders at 25 mm/sec paper speed. QT intervals were determined by averaging six complexes in lead II. Care was taken to avoid including U or P waves, and the QT intervals were measured from the onset of the Q wave (or the R wave if no Q wave was present) to the end of the T wave (junction with the isoelectric baseline). Only complexes with normal QRS and T waves were evaluated and no patient was taking medication which is known to alter the QT interval at the time of recording. Heart rate was calculated from the same complexes in which QT intervals were measured by averaging six R-R intervals in lead II. All QT intervals were corrected for heart rate (QTc) by dividing the QT by the square root of the R-R interval.27 Measurements were made on four separate occasions by two observers without knowledge of whether the patient was an aborted SIDS or a normal control. The QTc intervals of the aborted patients were plotted on the nomogram of QTc intervals derived by Alimurung et al.26 Results The general characteristics of these infants are shown in table 1. Physical and neurologic examinations were normal except in the six patients with transient postresuscitation
VOL 55, No 4, APRIL 1977
hypoxia, and laboratory data and chest and skull radiographs were also normal. The mean serum calcium level was 9.9 mm/100 ml (range 9.0 to 10.9). Electroencephalograms were normal except in two of the infants who had transient hypoxic changes. Pneumogram recordings in ten infants demonstrated episodes of prolonged sleep apnea (greater than 20 seconds). The QT intervals in aborted SIDS ranged from 0.20 to 0.33 seconds with a mean of 0.26 seconds compared to our normal infants in whom QT intervals ranged from 0.20 to 0.31 seconds with a mean of 0.25 seconds. The QTc for the aborted SIDS ranged from 0.35 to 0.42 seconds with a mean of 0.39 seconds compared to the QTc for normal controls which ranged from 0.34 to 0.43 seconds with a mean of 0.39 seconds. The QT intervals of our three infants who subsequently died from actual SIDS were 0.27, 0.28 and 0.28 and their calculated mean QTc was 0.39 seconds. Reports in the literature of 861 normal infants reveal a mean QTc of 0.39 seconds. The differences among the QTc in the aborted SIDS patients, the actual SIDS, our normal control infants, and reported normals in the literature25 26 were not statistically significant; and the QTc intervals in the aborted and actual patients were within the normal range when plotted on Alimurung's nomogram.2' To rule out possible age related QT variations, we compared our study and control populations by age as shown in table 2 and did not find significant differences in QTc intervals between these groups.
Discussion
While the etiology for SIDS is still unclear, review of our infants with aborted SIDS as well as three infants who subsequently were actual SIDS, reveals that QT interval prolongation is not present in these infants following resuscitation. Thus, unlike previous reports21' 22 which demonstrated QT prolongation in relatives of SIDS and thus suggested that QT prolongation is related to SIDS, we could not demonstrate QT prolongation in the aborted or actual SIDS infants themselves. In addition, as shown in table 2, we could find no age subgroup in which the QTc intervals differed from controls. Further strong evidence against involvement of QT prolongation in SIDS derives from the fact that the presumed mechanism for death in QT prolongation is ventricular fibrillation28 which in nearly all patients requires defibrillation; in none of our resuscitations was defibrillation needed. It has been suggested that QT prolongation may be related to sleep or activity,29-3' and it is therefore possible that our single ECG samples did not detect intermittent QT prolongation; however, evaluation of this requires continuous long-term ECG recordings. While it is conceivable that aborted SIDS is not the same
TABLE 1. Characterization of Aborted SIDS and Normal Control Infants Mean age
Mean weight (kg)
Sex M/F
Mean gestational age (weeks)
Mean birth weight
(kg) 21 Aborted SIDS 4.6 6.2 13/8 39 2.9 3 10.0* Subsequent actual SIDS 8.2 2/1 40 3.2 Normal control infants MGH 46 6.2 4.5 25/21 40 3.2 Normal controls literature25' 26 861 5.5 409/449 *Ages at the initial aborted SIDS episodes were 1, 3, and 7 months and at the actual SIDS episodes were 10, 8 and 12 months. No.
(months)
Downloaded from http://circ.ahajournals.org/ at BATH UNIV on June 27, 2015
635
QT INTERVAL IN SIDS/Kelly, Shannon, Liberthson TABLE 2. QTc Intervals in Aborted SIDS and Normal Control Infants by Age Age
No.
1 mo 2 mos 3 mos 4-6 mos 7-9 mos 10 + mos Total
5 6 2 3 2 3 21
Aborted SIDS QTc Range
.39 .40 .39 .40 .38 .38
.39
.35-42 .38-.42 .38.40
.39-.40 .36.40 .35-.42 .35-.42
Normal control infants (MGH) No. QTc Range
13 10 2 10 3 8
46
entity as actual SIDS and therefore that our study infants are not representative of the actual SIDS population, we believe this is not so because three of our study infants subsequently died of actual SIDS, six had significant clinical hypoxia demonstrating the severity of their aborted episodes, and ten infants had pneumogram documentation of prolonged, severe, and clinically significant apnea, which we believe could have precipitated actual SIDS. We conclude from our data that demonstrable QT prolongation is not present in resuscitated aborted SIDS, and therefore is unlikely to be a major cause for the sudden infant death syndrome.
Acknowledgment The authors wish to thank Kathleen O'Connell and Margaret Paolini for their assistance in the preparation of this study.
References 1. Bergman AB, Ray CG, Pomeroy MA, Wahl PW, Beckwith JB: Studies of the sudden infant death syndrome in King County, Washington, Ill. Epidemiology. Pediatrics 49: 860, 1972 2. Valdes-Dapena MA: Sudden, unexpected and unexplained death in infancy. A status report - 1973. N Engl J Med 289: 1195, 1973 3. Sudden Infant Death Syndrome: Proceedings of the Second International Conference on Causes of Sudden Death in Infants, edited by Bergman AB, Beckwith JB, Ray CG. Seattle, University of Washington Press, 1970 4. Naeye RL: Hypoxemia and the sudden infant death syndrome. Science 186: 837, 1974 5. Naeye RL: Pulmonary arterial abnormalities in the sudden-infant-death syndrome. N Engl J Med 289: 1167, 1973 6. Valdes-Dapena MA: Sudden and unexpected death in infancy: A review of the world literature. Pediatrics 39: 123, 1967 7. Marx JL: Crib death: Some promising leads but no solution yet. Science 189: 367, 1975 8. Steinschneider A: Prolonged apnea and the sudden infant death syndrome: Clinical and laboratory observations. Pediatrics 50: 646, 1972 9. James TN: Sudden death of babies. Circulation 53: 1, 1976 10. Downing S, Lee JC: Laryngeal chemosensitivity: A possible mechanism for sudden infant death syndrome. Pediatrics 55: 640, 1975
.39 .38 .40 .39 .38 .39 .39
.34,.43 .34-.42 .39-.40 .36,43
.35-.40 .35-.42 .34-.43
Normal controls literature's5 26 QTc No. Range
107 98 94 184 103 107 693
.39 .40 .40 .40 .40 .39 .40
.32-.46 .34-.47 .34-.47 .33-.49
.32-.45 .32-.45 .32-.49
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The role of the QT interval in the sudden infant death syndrome. D H Kelly, D C Shannon and R R Liberthson Circulation. 1977;55:633-635 doi: 10.1161/01.CIR.55.4.633 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1977 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
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