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Systolic Time Interval Characteristics in Children with Duchenne's Progressive Muscular Dystrophy


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964, 1982; Duchenne's muscular dystrophy, cardiomy

opathy, left ventricular dysfunction, systolic time inter vals, pre-ejection period/left ventricular ejection time prolongation.

Multifocal dystrophic areas, characterized by fi brosis at the cellular level and a total loss of thick and thin myofflaments at the subcellular level, are the histologic and ultrastructural hallmarks of car diomyopathy associated with the Duchenne type of muscular dystrophy (DMD).' Originally described by Perloff et al2 and later by others,@ these dys trophic changes show a peculiar predilection for the posterobasal segment and contiguous lateral or in ferior wall of the left ventricle.

Such extensive involvement ofthe left ventricular myocardium is apt to compromise its performance. During recent years, the value of systolic time in terval measurements (obtained from simultaneous high-speed recording of ECG, carotid pulse racing, and phonocardiogram) has become well-established as a sensitive noninvasive means of evaluating global left ventricular performance.@'4 However, information regarding STI characteristics in pa tients with DMD is scanty and controversial.'5―6 Preliminary studies by Bonnano et al'5 suggested that prolongation of pre-ejection period (PEP) was common in DMD and clearly differentiated patients from normal control subjects. By contrast, Goldberg et al'6 reported only PEP/left ventricular ejection time (LVET) ratio (determined from M-mode ech ocardiography), and observed no difference in the mean values between patients with DMD and nor mal control subjects. No details were given regard ABSTRACT.Systolictimeinterval(STI) characteristics

of 17 boys with Duchenne's muscular dystrophy (DMD) were compared with those of 80 normal boys who served as controlsubjects. The heart rate decreased linearly with age in normal control subjects (r = —¿.47,P < .01). By contrast, heart rate was significantly higher in patients with DMD (P < .001) and tended to increase further with age. Each STI variable for normal control subjects in creased significantly with age (P

@ .01); Qil, left ventric

ular ejection time (LVET), and pre-ejection period (PEP), in addition, decreased with increasing heart rate (P

@ .05).In dystrophic patients Qil and LVET decreased with increasing heart rate (P < .001) but were not influ enced by age. None of the other STI values in dystrophic patients was significantly influenced by either age or heart rate. Mean QII, LVET, and QI were shorter and PEP, isometric contraction time (ICT), and PEP/LVET ratio were longer (P < .001) for DMD patients than for normal control subjects. In 13/17 patients, QU and LVET were below the 95% confidence interval of the normal mean, whereas PEP, ICT, and PEP/LVET exceeded the upper limits of normal in 8, 9, and 11 patients, respec tively. For dystrophic patients, the difference (ti) between the observed values and those predicted from regression equations for normal control subjects was lower for Qil, LVET, and QI (P < .01) but higher for PEP (P < .04), ICT, and PEP/LVET ratio (P < .001). A Qil and i@LVET increased with age (P = .001 and .032, respectively). Duchenne's muscular dystrophy is thus documented to be associated with substantial alterations in STI charac teristics that suggest a compromise of global left ventric ular performance. Some of these abnormalities increase with age, probably reflecting the progressive cardiomy opathy characteristic of this disease. Pediatrics 70:958—

Received for publication Aug 24, 1981;accepted Feb 10, 1982.

Reprint requests to (S.K.S.) Cardiopulmonary Disease Service, St Jude Children's Research Hospital, 332 N Lauderdale, Mem phis, TN 38101.

PEDIATRICS (ISSN 0031 4005). Copyright ©1982 by the American Academy of Pediatrics.

Systolic Time Interval Characteristics in

Children with Duchenne's Progressive

Muscular Dystrophy

Shyamal K. Sanyal, FAAP, FACC, Ralph C. Tierney, FAAP, FACC,

p. Syamasundar Rao, FACC, Samuel E. Pitner, MD,

Stephen L. George, PhD, and Dennis R. Givins, MS


I—.-s1s2—--I ing other STI indices. Furthermore, neither of the

two studies provided information regarding STI characteristics in individual patients. We therefore studied STI characteristics in 17 boys with DMD and in 80 age- and sex-matched normal control subjects.

The purpose of the present communication is to report these observations and to discuss some of the factors that may influence STI characteristics in patients with Duchenne's muscular dystrophy.



Myocardial function of 17 boys, aged 5 to 16 years, was evaluated prospectively by noninvasive techniques. In each boy the diagnosis of Duchenne's type of progressive muscular dystrophy was made by a neurologist (S.P.) on the basis of clinical, biochemical, electromyographic, and muscle biopsy characteristics.' ECGs of all patients showed char acteristic features of Duchenne's muscular dystro phy,' namely, a deep Q wave in leads I to III and V4 to V6,and a tall R wave with an abnormal R/S ratio over V,. In addition each ECG showed normal sinus rhythm and normal QRS duration. All patients were normotensive and had normal ventricular de polarization. None had clinical signs of congestive heart failure or pneumonia, and none was receiving digitalis or diuretics at the time of these studies.

Determination of Systolic Time Intervals

Patients were studied in a resting, supine position after the procedure was carefully explained and a brief trial was performed to alleviate anxiety. The STI measurements were obtained from simultane

ous high-speed recordings of the ECG, phonocar

diogram, indirect-carotid pulse tracings, and respi ratory cycle (Fig 1),6.1719recorded by a multichan nel photographic system (MCPR, Cambridge In strument Co, Ossining, NY). The paper speed was

100 mm/sec for all recordings.@° The ECG lead that most clearly showed the onset of ventricular depo larization was selected for measurement. A 100- to 500-Hz frequency band was used to record the phonocardiogram. The microphone was placed in a position that provided the most clearly defined recordings of the initial high-frequency vibrations

of the first heart sound and the aortic component

of the second heart sound. Measurements of inspi ratory splitting of the second heart sound and of the relationship of the carotid incisura to the vibra tions of the second sound were used to confirm the aortic component of the second heart sound.

The carotid arterial pulsation was recorded6 with a funnel-shaped pickup connected to a Cambridge







FIg I . Methodusedto determinesystolictimeintervals from simultaneous high-speed recording of ECG, phono cardiogram (PHO), carotid pulse tracing (CAR), and res piratory cycle (RESP).

@ interval between initial high

frequency vibrations of first and second heart sounds; LVET, left ventricular ejection time; QS@, interval be tween Q wave of ECG to initial high-frequency vibration

of second heart sound.

transducer by polyethylene tubing (8 cm long and with a 4 mm internal diameter). Maximal gain was used and care was taken to obtain a tracing of at least 5 cm amplitude, with a sharply defined initial rapid upstroke and incisural notch.


From the above measurements, the following in tervals were calculated: PEP was derived by sub tracting LVET from QII; the interval from the beginning of depolarization to the first heart sound (QI) was derived by subtracting SI-Il from QII; and the isovolumic contraction time (ICT) was derived by subtracting LVET from SI-Il.

All intervals were calculated from the mean of measurements for 15 consecutive beats,2' each read to the nearest 5 msec. Care was taken to begin and end each series of consecutive readings with the same phase of respiration. Because of the diurnal variation in systolic intervals,@ all recordings were made between 8:30 @iand 12 PM.

Normal Control Group

Using identical techniques, we obtained similar measurements from 80 normal, healthy boys, aged 5 to 16 years. None of the children in this group had any evidence of congenital or acquired heart disease. All were normotensive.

Statistical Analyses

The purposes of the analysis were: (1) to assess

the effects of age and heart rate on the STI mea surements in dystrophy patients vs normal sub jects,'7@'9(2) to compare the dystrophy patients, as a group, with normal subjects using adjustment for age and heart rate as the basis of relationships found in (1). To determine the influence of age and heart rate on STI measurements, we used an ordi nary multiple linear regression model: Y = Bo + B,

+ xl + B2 X2, where Y represents the STI mea

surement for an individual; X1 is the individual's age in months; X2 is the individual's heart rate in beats per minute; and Bo, B,, and B2 are the con stants to be estimated from the data.

For each STI variable, the model was fitted in a forward stepwise fashion.23 A correlation coefficient (r), determined separately for each STI measure ment and age or heart rate, was used to assess the linear relationship between each pair of these van ables. The first variable entered into the equation (X, or X2) was the one more closely correlated with Y. The second variable was added only ifthe regres sion coefficient was significantly different (@.05 level) from zero after adjustment for the first vari able. If neither regression coefficient was signif icantly different from zero, then Y was assumed to be independent of both age and heart rate.

To compare the dystrophy patients with the nor mal subjects, we used the fitted regression equa tions for the normal subjects to determine the “¿predicted―values for each of the 511 variables for every patient with Duchenne's dystrophy. The dif ference between the observed and the “¿predicted―

STI measurement was then calculated. if the pop ulation of dystrophy patients were normal, one would expect the differences to have a distribution with a mean of zero. Thus, the differences between the mean values (adjustedand maladjustedfor age and heart rate) for patients with Duchenne's dys trophy and normal children were assessed by Stu dent's t test. Statistical computations were made on a Xerox Sigma IX computer, primarily with the Statistical Package for the Social Sciences (SPSS).@'


Age and Heart Rate

As shown in Fig 2, the heart rate of normal children decreased linearly with age (r = .47, y = 96.88 —¿0.14X,, where X, represents age in months P < .01). For patients with Duchenne's muscular dystrophy, however, heart rate tended to increase with age (r = .43, P = .70). Although significantly older than the normal group (148.6 ±37.4 months vs 115.4 ±4.1.7 months, P < .001), the dystrophic patients had an average heart rate that was consid erably higher than that ofthe normal children (99.1

± 15.7 beats per minute vs 80.6 ± 12.6 beats per

minute, P < .001).

Relationship of STI to Age and Heart Rate

All six STI variables from normal children showed significant prolongation with increasing age (P :S .01, Table 1). Multiple regression analysis indicated that only QII, LVET, and PEP were



@l20- •¿

Ui 00 - •¿

I.- .--. •¿

< ‘¿â€”@


60 ‘¿

@ ‘¿

@ I I i I i 1 i I

60 80 00 120 140 160 180 200

AGE (mos)

Fig2. Influenceof ageon heart rate in patientswith Duchenne's muscular dystrophy (dashed line) and nor mel control subjects (solid line). Heart rate for normal control children decreased linearly with age (r = .47, P

< .01) whereas heart rate in dystrophic patients tended


TABLE I RelationBetweenAge and Heart Rate and SystolicTime Interval (STI) Indices for 80 Normal Control Subjects and 17 Children with Duchenne's Muscular Dystrophy(DMD)STI

Variablet DMDAgeControl SubjectsChildren with

(mo) Heart Rate (beats/mm)Age

(mo) Heart Rate (beats/mm)r

P r Pr P r


.651 .001 —¿.608.001 LVET .455 .001 —¿.591 .001

PEP .539 .001 —¿.218.05

PEP/LVET .289 .01 .069 .542

QI .441 .001 —¿2.14.061

ICT .281 .012 —¿.061.589—.305

.232 —¿.832 .001 —¿.457.067 —¿.760.001 .160 .541 —¿.180 .489 .314 .219 .203 .436 —¿.300 .242 .204 .432 —¿1.04 .690 —¿1.02 .696

STI VariableMillisecondstRegression EquationSEQil370.8

±22.1397.2 ±0.25 M —¿ 0.68R15.1LVET289.3

±18.7335.0 ±0.10 M —¿ 0.72


±10.965.2 ±0.14 M9.2QI50.8

±7.641.5 ±0.08 M6.8ICT31.2

±8.624.5 ±0.06 M8.3PEP/LVET0.28±0.04

TABLE 3. Mean Valuesfor SystolicTime Interval (STI) Indices for Patients with Duchenne's Progressive Muscular Dystrophy (DMD) and Normal Control Sub jects*

* Abbreviations used are: LVET, left ventricular ejection time; PEP, pre-ejection period;

ICT, isometric contraction time. Values used in these comparisons were in milliseconds.

Test of significancefor Pearson'scorrelationcoefficient.

influenced by heart rate as well as age, and that QI,

ICT, and PEP/LVET ratio were not influenced by

heart rate, independent of age (Tables 1 and 2). For the group with Duchenne's dystrophy, QII and LVET were negatively correlated with heart rate (P < .001) but not with age (Table 1). Other STI measurements for the patients were not influ enced significantly by either age or heart rate.

Comparison of Children with Duchenne's Muscular Dystrophy and Normal Control


For the group of dystrophic children, the mean values for QII, QI, and LVET were significantly shorter (P < .001) and for ICT, PEP, and PEP! LVET ratio significantly more prolonged (P < .001) than the normal control values (Table 3).

Of the 17 dystrophic patients, QIl and LVET values were below the 95% confidence interval of the normal mean in 13 and QI,values were below normal in seven patients, whereas PEP and ICT values exceeded the upper limit of the normal mean in eight and nine patients, respectively. In 11/17 patients, PEP/LVET ratio also exceeded the upper limit of 95% confidence interval for the normal mean (Fig 3).

The difference between the observed and the predicted values for dystrophic patient is shown in Table 4. Predicted values were derived from the regression analysis of normal data (Table 2) as described earlier. The observed mean values for QII, LVET, and QI were significantly less than the mean predicted values (P < .001), whereas the mean observed values for ICT, PEP, and PEP/LVET ratio were significantly higher than expected (P < .05). In addition, the

@ valuesfor Qil and LVET in

dystrophic patients showed an increase with age (Fig 4).

TABLE 2. RegressionEquationsfor CalculatingSys tolic Time Interval (STI) Duration from Results for 80 Normal Control Subjects (Boys Aged 5 to 16 Years)

* Abbreviations used are: M, age in months; R, heart rate

in beats per minute. Other abbreviations are defined in

Table 1 footnote.

t Values




STI VariabletControl



with DMD


rate (beats/ruin)80.6 ±12.699.1 ± 15.7QII370.8

±22.0331.7 ± 15.9LVET289.3

±18.6238.9 ± 14.7PEP81.5

±10.892.8 ± 11.4QI50.8

±7.541.9 ± 6.0ICT31.2

±8.551.1 ± 9.2PEP/LVET0.28

±0.040.4 ±0.06 * Abbreviations are defined in Table 1 footnote. Level of

significance based on Student's t test in all cases was P

< .001.

t STI valuesaremeasuredin milliseconds(mean±SD).




±15.9238.9 ±14.792.8 ±11.40.39 ±0.0641.9 ±6.051.1 ± 9.2Predicted366.8

±10.7279.5 ±10.286.2 ±5.30.30 ±0.0153.4 ±2.333.4 ± 2.2Difference—35

±13.4t—40.6 ±hOt6.7 ±11.8@0.10 ±0.06@—11.5 ±5.9t17.7 ±9.7t

o@ @

@ @ @

@ I


@ i I i I

. 60 80 00 20 40 60 I@O 200

AGE (mos)

Fig 3. Pre-ej'@ctionperiod (PEP)/left ventricular ejec tion time (U @T)ratios in patients with Duchenne's muscular dy3@rophy. Each dot represents PEP/LVET ratio for one patient. For 11/17 patients, PEP/LVET ratio exceeded upper limit of 95% confidence interval (top border of shaded area) of normal mean (shown by unbro ken line).

TABLE 4. DifferencesBetweenObservedand Predicted

Duchenne's Muscular Dystrophy*

0 —¿â€˜

@ ‘¿

@ I I i


@ H


document that STI characteristics in patients with in a substantial number of boys with this disease.

Duchenne's type ofprogressive muscular dystrophy The differences include decreases in the duration of differ strikingly from those of normal control sub- electromechanical systole (QIl) and LVET with jects and suggest global left ventricular dysfunction concomitant increases in ICT, PEP, and PEP!

LVET ratio.

@ The three main determinants of the duration of

. systole and its phases are venous return, arterial

0 5 - resistance, and changes in heart rate. All of our

. •¿ patients were normotensive, with normal sinus

@ •¿ rhythm. None had evidence of congestive heart

0 4 - •¿â€¢¿ •¿â€¢¿_i,_• failure, dehydration, or shock, and none was receiv

___..__, —¿.—--@—@ ;-—---—----—.—_ ing digitalis or other inotropic drugs. An increase in •¿â€¢¿ •¿ heart rate, however, was a common finding in our

0 3 -S.----— patients. Since the original work by Wiggers26 on

the laws that govern the duration of ventricular

—¿@ —¿..-—@— —¿ systole and its phases, it has become well estab


-@ _ _@

@ —¿@

@ lished that increased heart rate alone can shorten

II and LVET.2732 In the absence of extramyocar

@ dial conditions that could alter venous return or

arterial resistance, sinus tachycardia seems to be a prime cause of the abbreviated systole (particularly LVET) in dystrophic patients (Fig 5). In addition to alterations in Qil and LVET, the PEP was significantly prolonged so that PEP/LVET ratios were abnormally elevatedfor a substantialnumber of our patients.

The pre-ejection period consists of a QI interval

Values for Systolic Time Interval (STI) in Patients with



w >




a-* Abbreviations are defined in Table 1 footnote. All values are given in milliseconds (mean ± SD).

t P< .01,based


t test.

:1:P < .05, basedon Student'st test.



@ .621

r :763

p :<003

p:(000I n:17

n:17 •¿

•¿â€¢ 50 •¿

40- —¿


-;:;@( a,U)



I_40-@:1 uJ

0 >



60 80 00 20 40 60 80 200


enne's muscular dystrophy. Difference from predicted normal values increased significantly with age for QII (P < .001) as well as for LVET (P < .03).

I I i

@ i I

@ I i I

@ I

80 00 20 40 60 80 200

AGE (mos)

Fig 4. Influence of age on difference (is) betweenob


360 - 280


-. I

320- •¿ •¿

r : —¿.832

300 - p:(000I

n :17

I .

@ . . I

@ . . .

@ . . .

@ @

@ . . . I

@ . . .






@ . . . I

@ @

@ . I

@ . . . I . . . . I .

@ . .




‘¿@“8090 00 110 20 13Ô 40


Fig 5. Influenceof heart rate on Qil (left) and left ventricular ejection time (LVET) (right) in Duchenne's muscular dystrophy. Each circle represents systolic time

and an ICT. In most of our patients, QI was short, whereas ICT was prolonged, suggesting that the latter is a major determinant of prolongation of

PEP in children with DMD. The genesis of a pro

longed ICT in DMD is not known. Cardiomyopathy forms an integral part of DMD.2'3 We have prey ously shown@,s@a@that a total loss of thick and thin myofilaments of the ventricular myocardium is the main ultrastructural change in these patients and that such changes involve, most extensively, the posterobasal segment of the left ventricle followed by, in order of decreasing severity, the posterior papillary muscle, interventricular septum, and the free walls of the right and left ventricles. That such widespread loss of contractile elements would sub stantially compromise the intrinsic contractile state

of the ventricular myocardium and decrease the

isometric tension as well as the maximum rate of tension development,@ seems logical. A slow rate of myocardial force development, in turn, would increase the time required for intraventricular pres sure to rise above aortic diastolic pressure, thereby prolonging ICT.@

The value of STI measurements for detecting global left ventricular dysfunction is substantially enhanced by determining the PEP/LVET ratio. Since this ratio may indicate left ventricular dys function when either PEP, or LVET, or both are still within the normal range, it represents the single most useful STI measurement for evaluating global left ventricular performance. In our study, the PEP/LVET ratio exceeded the upper standard for age- and sex-matched normal control subjects in 11/17 children, indicating that global left ventricu lar dysfunction is common in children with DMD, especially older children. None of these patients



@ 240



80 90 100 110 20 30 40


interval (STI) measurements for one patient. Both Qil and LVET in dystrophic patients are negatively corre lated with heart rate (both P < .001).

had hypertension, abnormal ventricular depolari zation, congestive heart failure, anemia, sepsis, shock, or dehydration. In the absence of extramy ocardial factors, which could alter the preload or after load conditions and hence STI measure ments,7'9'@ prolongation of PEP and ICT, we be lieve, reflect an altered state of myocardial contrac tffity9'@°resulting from a loss of contractile elements due to progressive dystrophic involvement of the heart.'5'4'

Thus, STI abnormalities are common in children with Duchenne's muscular dystrophy and reflect an intrinsic weakness of ventricular myocardium sec ondary to widespread loss of contractile elements. Serial study of STI characteristics provides a sim ple, easily reproducible and noninvasive means of evaluating the progression of cardiomyopathy in these patients.


This study was supported by research grant CA-21765 from the National Cancer Institute and by ALSAC.

The authors wish to thank Dr David H. Spodick for critical review of the manuscript and Jane Seifert for editOrial assistance.


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JMed 287:677, 1972

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George and Dennis R. Givins

Shyamal K. Sanyal, Ralph C. Tierney, P. Syamasundar Rao, Samuel E. Pitner, Stephen L.

Muscular Dystrophy

Systolic Time Interval Characteristics in Children with Duchenne's Progressive


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George and Dennis R. Givins

Shyamal K. Sanyal, Ralph C. Tierney, P. Syamasundar Rao, Samuel E. Pitner, Stephen L.

Muscular Dystrophy

Systolic Time Interval Characteristics in Children with Duchenne's Progressive


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Fig 3.Pre-ej'@ctionperiod (PEP)/left ventricular ejectiontime(U@T)ratiosin patientswithDuchenne'smusculardy3@rophy.EachdotrepresentsPEP/LVETratio for one patient.For 11/17 patients,PEP/LVETratio exceededupperlimit of 95% confidenceinterval(topborder of shaded area) of normal mean (shown by unbroken line).


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Face mask therapy for growing individuals produces predictable maxillary protraction against the prognathic mandible.. Keywords: Face mask therapy, Growing individuals, Maxillary

(2004) reported a limited randomised double-blinded, placebo-controlled trial investigating the use of phenytoin for the prevention of early post- traumatic seizures in children

• 05-ECRP-FP037: New Migration Dynamics: Regular and Irregular Work on the European Labour Market; • 05-ECRP-FP041: Migration and Networks of Care in Europe: A Comparative