Serial Echocardiographic and Doppler Diastolic Filling in Full-Term Neonates
Evaluation
Jose C. Areias,
MD,
MD,
Robin Meyer,
RN,
William
A. Scott,
uantitative structural differences exist between fetal and adult myocardium.’ In the fetus, noncontractile tissue constitutes about 70% of muscle mass in contrast to findings in the adult myocardium in which From the Departments of Pediatrics and Physiology, University of Porto, Porto, Portugal, and the Department of Pediatrics and Children’s Research Center, University of Arizona, Health Sciences Center, 1501 North Campbell Avenue, Tucson, Arizona 85724. This study was supported by the Pediatric Cardiology Research Fund, University of Arizona, Health Sciences Center, Tucson, Arizona and the Junta National de Investigacas Cientifica e Technologica, University of Porto, Porto, Portugal. Manuscript received December 11, 1989; revised manuscript received and accepted February 20,199O.
of Left Ventricular
and Stanley J. Goldberg,
MD
noncontractile elements represent only about 40?6 of muscle mass.’ Friedman2 studied isolated myocardium and showed that there was less active tension and higher passive stiffness in fetuses than in adult lambs, suggesting that fetal myocardium is less compliant than adult myocardium. Previous echocardiographic and Doppler studies in fetuses and neonates detected a pattern of mitral velocities showing a lower E-wave amplitude when compared with later normal mitral E peaks.394These studies detected less early left ventricular (LV) filling in fetuses and neonates that could be related to diminished relaxation and higher muscular stiffness. Previous investiga-
IVRT MITRAL
FIGURE l.lsovobnicrekxatbtime.Top, all M-msds dlowing nlltrd valve opwling. 6OROfIl,~M-llIOdSShSwing~V*Cb-
swe.Dotrsdhtssamprojectsdtoshowths cEfhemeintime.limeisQpictadontopof uppsr pansl. Ead~ long namw cates1GGms.lvRT=lsovohmnictims.
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madi
indi-
to& followed diastolic LV function in neonates up to the first 4 days of life and, therefore, did not determine the pattern of functional diastolic maturation. Further, prior studies of the neonate have not assessed LV isovolumic relaxation time by serial noninvasive measurement. Our study evaluates, by serial echocardiography and Doppler observations, the LV diastolic filling pattern in full-term neonates after birth and during the first 3 weeks of life to observe the natural evolution in LV diastolic function. The study group consisted of 21 full-term neonates selected from the newborn nursery of the University of Arizona Health Sciences Center. Permission for this study was obtained from parents by written consent and the study was approved by the human subjects committee. No infant had evidence of cardiac disease on a previous pediatric examination. Echocardiographic and Doppler studies were performed in all cases during thefirst 36 hours and repeated during the second and third weeks of life. All subjects were studied with a range-gated pulsed Doppler echocardiographic device (Biosound Inc.) operating at a cen-
terfrequency of 5 MHz. A complete 2-dimensional echocardiographic examination was initially performed to detect any possible cardiac abnormality. Presence of a patent ductus arteriosus was evaluated by examining pulmonary artery velocities. Foramen ovale shunting was evaluated by recording velocities on either side of the atria1 septum. Echocardiographic and Doppler tracings were recorded simultaneously with an electrocardiogram on a strip-chart with tracing speed set at 75 mm/s. All children were studied during natural sleep. LV isovolumic relaxation time (ms) was evaluated by using Mmode determination of the interval between aortic closure and mitral opening. Valve traces were recorded sequentially at similar heart rates (Figure 1). An average of 3 consecutive measurements was always reported. Measurements were performed with a digitizing device that had an X and Y resolution of 0.1 mm. For diastolic LV Doppler studies, the sample volume was located between mitral leaflets at the level of the tips. Spatial alignment of ultrasonic beam and flow was accomplished by transducer manipulation until the highest
MITRAL
VELOCITIES
FIGURE 2. Mitral velocities obtained from a5inglechildoverthecoufseofthestudy. Far leff shows an E wave that is of lower amplitude than the A wave and dtastolii mitralregurgitationaftertheEandtheA wave. The middfe, abtained during the second week of Iii, has the same velocity callbratlon as the far left. The E wave has progremed in amplitude. The far right has avdocityscakontheright.Eachsmall madc equals 20 cm/s. Note the further amplitude increase of the E velocity.
c 1.5 DAYS MlTRAL
2nd WEEK
DIASTOLIC .T
FIGURE 3. Mitral diastdic regurgitation. tral &stolii regurgitation is visualized the E wave (arrow) in all 3 beats.
3rd WEEK
REGURGITATION v
Miafter
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TABLE I Comparison of Ventricular Filling Parameters for Less Than 1.5 Days, and During the Second and Third Week Day 1.5 LIVRT
41 f 12
MDT E/A ratio E peak A peak HR (beats/min)
Week 2
Week 3
47+12
51f8 84%
p Value <0.004*
62f14 1.08f0.2
87flO 1.12fO.l
1.25iO.l
<0.004*
55f8
55i8
65f16
<0.002*
49f7
52f9
49f8 120* 14
129fll
135*
11
NS 12
<0.002*
Values are expressed as mean f standard devlatlon. *Significant difference between day 1.5 and week 3: + slgniflcant difference between day 1.5 and week 2; *significant difference between weeks 2 and 3. LIVRT = left isovolumic relaxation time (ms): MDT = mitral decekratlon time (ms): NS = not significant.
spectral velocities were obtained. Peak modal velocities (cm/s) of E and A waves were used for measurement. Mean deceleration time (ms) was determined by evaluating the time interval between peak E velocity and the crossover of descendent E slope with 0 baseline. When atria1 contraction occurred before the mitral deceleration slope had decreased to the 0 baseline, the slope was linearly extrapolated to the baseline. Results are expressed as mean f standard deviation. Statistical analysis was performed with repeated measures analysis of variance. For paired differences, Scheffe’s test was used. Linear regression analysis was used to compare changes in E velocities and heart rate. A p value CO.05 was considered statistically significant. Fifty-six echocardiographic and Doppler studies were performed in 21 neonates. Gestation ranged from 37 weeks to term. Birth weight rangedfrom 2.6 to 4.1 kg. Mean time for the study was 60 minutes. No patient was excluded because of unacceptable quality of recordings. For the repeated measures analyses, only data for the I4 patients who had measurements at each time interval were considered. The data are listed in Table I. Mean LV isovolumic relaxation time increased significantly between the initial and third measurements. Mean mitral deceleration time increased significantly between the first and second measurement but did not change significantly thereafter. Similarly, the mean E/A ratio increased significantly from thefirst to the third evaluation. This was primarily due to an increase in E amplitude over the same time period. Figure 2 shows morphologic progression of the E and A waves in a typical single patient. Mean heart rate increased from day 1.5 to the third week. Heart rate showed an inverse relation to peak mitral E wave between day 1.5 and thereafter (r = -0.50). At the time of thefirst evaluation, Doppler sampling of main pulmonary artery depicted a patent ductus arteriosus in 15 (71%) of 21 neonates. No signijicant difference in any studied variable was found when data were compared for neonates with a patent ductus arteriosus and those without. No signtjicant foramen ovale shunts were detected in either direction. Middiastolic velocity reversal (Figure 3) was noted after the E wave in 16 neonates studied during the first 36 hours. This finding persisted in 3 subjects during week 2 and disappeared thereafter. A localized area of 110
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diastolic mitral regurgitation velocities after atria1 contraction was noted in all children during the 3 weeks of study. The most important finding of this serial study of LV diastolic function was the demonstration of changing ventricular relaxation and compliance. Cardiac relaxation starts at approximately the time of semilunar valve closure and includes the passive diastolic ventricular filling. Accordingly, relaxation should be related to isovolumic relaxation time and Doppler mitral E velocity.6 Compliance, a late diastolic phenomenon, should be related to Doppler mitral velocity at atria1 contraction.6 To date, few studies have been published regarding LV diastolic function in the neonate as measured by Doppler and none included data beyond the first 4 days of life. Riggs et al4 observed a mean peak mitral E/A ratio of 1.15 for the first day and 1.00 for day 2. Wilson et al5 found insignificant differences in E/A ratio for neonates studied during the first 24 hours or at 4 days. In our study, mean peak E/A ratio did not change significantly during the first 2 weeks but increased significantly between weeks 2 and 3. This change in E/A ratio in our study was related to a significant increase in E amplitude without changes in A. During our study, mean heart rate did not change significantly from the second to the third week and therefore, heart rate should not have influenced mitral velocity amplitudes during this period. Accordingly, enhanced ventricular filling in early diastole suggests an improvement in relaxation. In our study, a progressive increase in isovolumic relaxation time was found between successive measur ments. Middiastolic mi ral regurgitation occurred in 16 neonates at day 1.5, per isted in only 3 subjects during week 2 and disappeared the \ eafter. This middiastolic flow reversal is an indicator of ventricular pressure exceeding atria1 pressure during early filling. Disappearance of this flow reversal after the first day of life is an indirect indication of improved diastolic LV compliance with time. Low velocity mitral regurgitant flow after atria1 contraction was noted in all children and in all serial evaluations and, therefore, was probably not a factor in the mitral velocity differences observed. Mitral deceleration time is related to the LV rapid filling wave amplitude and correlates inversely with LV pressure. Results of our study showed that mitral deceleration time increased from day 1.5 to week 2, suggesting a lower early diastolic cavity pressure and muscular stiffness and therefore, improved ventricular compliance. A patent ductus arteriosus was detected in 15 immediate postnatal subjects; no significant differences were detected when comparing data of those with a patent ductus arteriosus to data of those without. These results are similar to those reported by Riggs et al4 and suggest that for full-term neonates, a patent ductus arteriosus does not influence diastolic ventricular function during the first 2 days of life. Multiple interacting factors influence the pattern of LV diastolic filling and include atria1 and ventricular factors. Major left atria1 factors are pressure and compliance. LV factors include pressure, relaxation and compliance. Nonevf these factors were measured directly in our
study. Moreover, during ventricular diastole, it is possible that some overlap exists between relaxation and compliance and our study did not identify the area of overlap.* Peak velocities and mitral deceleration time are influenced to some extent by sample volume location. In our study, the sample volume was always positioned between mitral leaflets tips. Accordingly, the constancy of sample volume location limited uncertainties that could influence our results.3 A potentially greater problem was related to the M-mode evaluation of LV relaxation time. Aortic closure and mitral valve opening were not measured in the same heart cycle. We measured intervals at equal heart rates for the 2 tracings. Further, all measurements were averaged for 3 cardiac cycles. Although neonates were always studied while asleep, minor heart rate differences between cardiac cycles could introduce modest imprecision into computation of LV isovolumic relaxation time.
Ruptured Chordae of Endomyocardial Alan C. Braverman,
MD,
Our study detected a transitional diminished postnatal ventricular relaxation and compliance in full-term neonates and a subsequent improvement in these measurements during the first 3 weeks of life. 1. Heymann MA. Fetal and neonatal circulations. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Heart Disease in Infants, Children, and Adolescents. Baltimore: Williams & Wilkins, 1989:24-34. 2. Friedman WF. The intrinsic physiologic properties of the developing heart. In: Friedman WF, Lesch M, Sonnenblick EH, eds. Neonatal Heart Disease. New York:
Grune
& Stratton,
JACC
1989;13:7Ot-705.
5. Wilson N. Reed KL. Allen HD. Marx GR. Goldbere SJ. Donoler echocardiographic observations of pulmonary and transvalvnlar &city changes after birth and during the early neonatal period. Am Heart J /987;113:750-758. 6. Devereux RB. Left ventricular diastolic dysfunction: early diastolic relaxation and late diastolic compliance. JACC /989;13;337-339.
Tendineae of the Tricuspid Biopsy in Heart Transplant Sharon E. Coplen,
MD,
Valve as a Complication Patients
Gilbert H. Mudge,
ercutaneous transvenous endomyocardial biopsy is P the preferred method to detect graft rejection in the transplanted heart. This procedure has undergone improvements and modifications making endomyocardial biopsy safe from the right internal jugular or femoral venous approach. ly2 Large series have documented the low morbidity and mortality associated with endomyocardial biopsy. Major complications include cardiac perforation and tamponade occurring in <0.4%.‘,* Other cardiac complications are arrhythmias, bundle branch block and endocarditis. Recently, coronary arterial-right ventricular tistula secondary to repeated endomyocardial biopsies has been described.3 With improved survival in cardiac transplant patients, complications of repeated endomyocardial biopsies may become more apparent. This report describes 5 patients with orthotopic cardiac transplants who have echocardiographic evidence of tricuspid valve chordal rupture as a complication of endomyocardial biopsy. The study included 81 patients who underwent 82 orthotopic heart transplantations at Brigham and Women’s Hospital. Each patient underwent right ventricular endomyocardial biopsy during the period from December 1988 through November 1989 to evaluate the presence and severity of allograft rejection. At least I echocardiogram followed the last endomyocardial biopsy. At Brigham and Women’s Hospital, biopsies areperformed weekly for 1 month after transplantation and From the Cardiovascular Division, Department of Medicine, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115. Dr. Lee is a recipient of Physician Award HL-01835 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. Manuscript received December 27, 1989; revised manuscript received and accepted February 26, 1990.
1973:21-49.
3. Reed KL, Meijbeom EJ, Sabn DJ, Scagnelli SA, Valdes-Cruz LM, Shenker L. Cardiac Doppler flow velocities in human fetuses. Circulation 1986:73:41-46. 4. Riggs TW, Rodriguez R, Snider AR, Batton D. Doppler echocardiographic evaluation of right and left ventricular diastolic function in normal neonates.
MD,
and Richard T. Lee,
MD
then biweekly for 2 months. After the third month biopsies are performed monthly for the next 9 months. After the first year after transplantation, patients undergo biopsies on a 6- to I2-month interval or more frequently if rejection is apparent. A total of 440 biopsy procedures were performed in the 82 orthotopic transplants with a total of 1,442 individual biopsy specimens obtained. Thus, an average of 5.4 biopsy procedures (I 7.4 biopsy specimens)/heart transplant were performed in this 12month period (range I to 16 biopsy procedures with 3 to 51 biopsy specimens/patient). Right ventricular biopsy was performed in 93% of patients via the right internal jugular approach with a standard (Caves-Schulz) bioptome usingjluoroscopic guidance. Seven percent of biopsies were performed from the right femoral vein using a Cordis bipal or Mansfieldfemoral bioptome. The femoral approach was used when endomyocardial biopsy was beingperformed at the time of coronary arteriography in an annual posttransplantation evaluation. Echocardiographic imaging was performed using a Hewlett Packard 77020 AC/AR ultrasonoscope device and a 2.5- or S-MHz transducer. Severity of tricuspid regurgitation was semiquantitated by pulsed wave or color-flow Doppler using a scale from 0 to 4+ on the basis of the area of the systolic flow disturbance relative to the area of the right atrium. The diagnosis of ruptured tricuspid valve chordae tendineae was made by 2-dimensional echocardiography as prolapse of chordal elements into the right atrium during systole.4 Five patients (6.2%) were identified with echocardiographic evidence of tricuspid valve chordal rupture. In each of these patients chordal tissue from the posterior tricuspid valve leaji’et was seen to prolapse into the right atrium during systole (Figures 1 and 2). No ruptured THE AMERICAN
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