Strain cardíaco na avaliação da função cardíaca fetal

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Strain cardíaco na avaliação da função cardíaca fetal

  1. 1. C 2008, the Authors Journal compilation C 2008, Wiley Periodicals, Inc. DOI: 10.1111/j.1540-8175.2008.00761.x Global Longitudinal Cardiac Strain and Strain Rate for Assessment of Fetal Cardiac Function: Novel Experience with Velocity Vector Imaging Piers C.A. Barker, M.D.,∗ Helene Houle, B.A.,† Jennifer S. Li, M.D.,∗ Stephen Miller, M.D.,∗ James Rene Herlong, M.D.,∗ and Michael G.W. Camitta, M.D.∗ ∗ Duke Children’s Heart Program, Duke University Medical Center, Durham, North Carolina; and †Siemens Medical Solutions, Mountain View, California Background: Cardiac strain and strain rate are new methods to quantitate fetal cardiac function. Doppler-based techniques are regional measurements limited by angle of insonation. Newer feature- tracking algorithms permit angle independent measurements from two-dimensional datasets. This report describes the novel measurement of global strain, strain rate, and velocity using Velocity Vector Imaging (VVI) in a group of fetuses with and without heart disease. Methods: Global and segmental longitudinal measurements were performed on the right and left ventricles in 33 normal fetuses and 15 fetuses with heart disease. Segmental measurements were compared to global measurements. Clinical outcome data were recorded for fetuses with heart disease. Results: Forty-eight fetuses were evaluated with VVI. Cardiac strain and strain rate in normal fetuses were similar to normal adult values, but lower than pediatric values (LV strain = −17.7%, strain rate −2.4/sec; RV strain = −18.0%, strain rate −1.9/sec). No difference was present between segmental and global measurements of cardiac strain and strain rate, although basal and apical velocities were significantly different from global velocities for both right and left ventricles. In fetuses with heart disease, lower global cardiac strain appeared to correlate with clinical status, although there was no correlation with visual estimates of cardiac function or outcome. Conclusion: Measurement of global longitudinal cardiac strain and strain rate is possible in fetuses using VVI. Segmental measurements are not significantly different from global measurements; global measurements may be a useful tool to quantitate fetal cardiac function. (ECHOCARDIOGRAPHY, Volume 26, January 2009) fetal echocardiography, cardiac strain, velocity vector imaging Quantification of fetal cardiac function has long been an elusive goal in the evaluation of fetal cardiac physiology and adaptation to disease. The fetal circulation is unique in its source of oxygenated blood, degree of intracar- diac and extracardiac mixing, and output of the right and left ventricles.1 Measurements of car- diac function validated in adults, such as the shortening fraction or ejection fraction, often fail to provide accurate results in fetuses due to intrinsic differences in fetal wall motion and small ventricular volumes that magnify mea- surement error. More recently, measurement of fetal cardiac strain and strain rate has been Address for correspondence and reprint requests: Piers C. A. Barker, M.D., Room 7502D, Duke Hospital North, Box 3090, Durham, NC 27710. Fax: +1-919-681-7892; E-mail: piers.barker@duke.edu attempted to overcome the limitations of two- dimensional and M-mode imaging.2–4 Myocardial strain is defined as the change in length of an object relative to its baseline length caused by an applied stress, with5 strain rate being derived from the velocity of the de- formation over time.6 In the practice of cardiac ultrasound, the strain rate is typically mea- sured using tissue Doppler imaging to calculate the velocities of two points set a small, fixed distance apart, with cardiac strain then calcu- lated as the integral of the strain rate measure- ment.6 By analyzing segments of myocardium directly rather than changes in ventricular di- mensions or volumes, cardiac strain, and strain rate may be better measurements of ventricu- lar contractility.7 However, assessment of only certain small segments of myocardium limits the extrapolation of these segmental results to global cardiac function. 28 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 26, No. 1, 2009
  2. 2. FETAL GLOBAL LONGITUDINAL CARDIAC STRAIN AND STRAIN RATE Both regional cardiac strain and strain rate have been reported and validated as measures of ventricular function in adults and children.6 However, the majority of these studies have been based upon tissue or color Doppler mea- surements, including the first fetal studies.4,8,9 Tissue Doppler measurements have the advan- tage of less reliance on image quality and bor- der detection, and permit the acquisition of data at much higher frame rates than those available by traditional two-dimensional ultra- sound or cardiac magnetic resonance imaging.6 However, tissue Doppler is inherently limited by its dependence on the angle of insonation, which permits analysis of only those limited segments of myocardium that are parallel to the ultrasound beam, and can be affected by re- gional cardiac translation.10 Both of these lim- itations pose significant problems in fetal pa- tients, given the variation in fetal position, and prevent measurement of global indices for the left or right ventricle. Speckle or feature tracking is a novel way of assessing myocardial motion from the two- dimensional B-mode image. As opposed to tissue Doppler, “speckles” derived from the sta- ble interference and backscatter of the ultra- sound signal in the myocardium are tracked from frame to frame with reference to their pre- vious position and distance of movement.7,11,12 From these data, both the velocity and the di- rection of myocardial motion (the velocity vec- tor) can be calculated for any region of the myocardium, regardless of angle to the ultra- sound beam, with strain rate and strain cal- culated by comparing adjacent velocity vectors. Further refinements of this tracking technique allow for the incorporation of manually traced borders, annuli position, and speckle periodic- ity to create the potentially more accurate “fea- ture” tracking software used in this study.7,11 This method has been validated in adult pa- tients for the calculation of cardiac strain and strain rate,13 but the application to fetal pa- tients has only recently been reported, and only in normal fetuses.2,3,14 Recently, feature- tracking techniques have been applied to assess global cardiac strain and strain rate in animal infarct models and humans after myocardial in- farction, in whom regional measurements may not accurately reflect cardiac function due to injured segments,15 as well as in adults with systemic right ventricles to overcome the lim- itations of right ventricular (RV) geometry.16 However, this method has not yet been fully studied in fetal patients, whose small cardiac size and different physiology limit the useful- ness of regional measurements. We therefore report our experience in the novel use of velocity vector imaging (VVI) to calculate global cardiac strain, strain rate, and velocity in a series of fetuses with and without heart disease. Methods Longitudinal cardiac strain, strain rate, and velocity analysis was performed on the fe- tal right ventricle and fetal left ventricle (if present) obtained during a clinically indicated fetal echocardiogram. The study was approved by the Duke University Medical Center Institu- tional Review Board for Human Research and all subjects consented to participate. A research version of the commercially available VVI soft- ware (Siemens Medical Solutions, Mountain View, CA, USA) was used for all measurements. For each fetus, a high-resolution, zoomed loop of the apical four-chamber view incorpo- rating at least one complete cardiac cycle was recorded, with machine settings adjusted to maximize frame rate. This image was stored digitally and transferred to the offline worksta- tion (Syngo USWP, Siemens Medical Solutions) for later analysis. Syngo VVI was launched from review of each DICOM digital clip. R-wave gating was performed using a superimposed M-mode tracing of left or RV wall motion to define the onset of ventricular systole (initial in- ward motion of the ventricular wall) as a corol- lary of the electrical QRS and therefore the be- ginning and end of a cardiac cycle. This method of R-wave gating was also used for fetuses eval- uated during an arrhythmia, with the cardiac cycle selected as representative of baseline si- nus rhythm (i.e., not during or at the onset or termination of the abnormal rhythm). After definition of the cardiac cycle, the en- docardium of the right and left ventricles was traced manually from a single frame of the digital loop that provided the clearest still- frame endocardial border definition (typically mid-systole). The same cardiac cycle was used for both the left ventricular (LV) and RV trac- ing, except in three normal fetuses and two abnormal fetuses in which separate apical four-chamber views were required. Endocar- dial tracing began at the edge of the atrioven- tricular valve annulus, extended to the apex of the ventricle without incorporation of the papillary muscle complex, and returned basally to the other edge of the atrioventricular valve Vol. 26, No. 1, 2009 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 29
  3. 3. BARKER, ET AL. annulus. This therefore provided both the bor- der and annuli position information necessary for the “feature-tracking” component of the VVI algorithm. Twenty-two individual, equally spaced velocity vectors were then automatically calculated for each frame of the cardiac cycle by the VVI algorithm and displayed for the complete loop. Accuracy of border tracking was visually confirmed by viewing the cardiac cy- cle with only border information displayed (i.e., with velocity vectors removed). If necessary, in- dividual regions of the border were adjusted until the border was correctly tracked for each frame. Cardiac strain, strain rate, and velocity data were automatically calculated from the veloc- ity vector information, and displayed in a six- segment model for both fetal ventricles. In addi- tion, the global peak systolic strain, global peak systolic strain rate, and global peak systolic ve- locities were calculated from the entire velocity vector dataset as an average of all segments of ventricular motion, and displayed as a separate curve. Statistical Testing Global longitudinal cardiac strain, strain rate, and velocities were compared to regional measurements using Student’s t-test for both normal fetuses and fetuses with heart disease. A P-value of < 0.05 was used to define a signif- icant difference. Interobserver variability was tested between two observers (PB and HH) on ten randomly selected datasets and intraob- server variability was tested for two observers (PB and HH) on five randomly selected datasets using coefficient of variation analysis. For fetuses with heart disease, global longitu- dinal cardiac strain and strain rate were com- pared to visually estimated function (hypercon- tractile, normal, mildly decreased, moderately decreased, and severely decreased, as recorded by a skilled independent observer (MC) blinded to the results of the strain analysis) and ulti- mate fetal outcome. No comparisons were made between abnormal fetuses as a group and nor- mal fetuses due to the heterogeneity of fetal cardiac diagnoses. Results Forty-eight fetal patients were enrolled in the study, consisting of 33 fetuses with normal cardiac anatomy and function, and 15 fetuses with congenital or functional heart disease. The median gestational age was 24 weeks (range 17–38 weeks). Four fetuses with congenital or functional heart disease underwent multiple echocardiograms, permitting serial analysis of fetal strain. Accurate endocardial border track- ing and calculation of velocity vectors were ac- complished on all right and left ventricles in all fetuses despite limitations in image qual- ity secondary to fetal position or maternal body habitus, with the exception of one left ventricle in a single abnormal fetal patient due to exces- sive fetal motion. Longitudinal cardiac strain measurements were possible in all tracked fe- tuses, while strain rate and velocity measure- ments were limited to 22 normal fetuses and 12 abnormal fetuses due to compression of frame rate/time data in the other fetuses. Figure 1 demonstrates typical LV velocity vectors and the resultant strain calculations for a normal 24-week fetus. Table I demonstrates the results of global and segmental longitudinal strain analysis for both left and right ventricles in normal fe- tuses. The mean LV global peak systolic strain was −17.7% (standard deviation 6.4) with a median of −16.6% (range −9.2% to −32.9%). The mean RV global peak systolic strain was −18.0% (standard deviation 6.4) with a median of −17.4% (range −6.7% to −33.4%). There was no statistical difference between global strain and segmental strain measurements for either ventricle. Table II demonstrates the results of global and segmental longitudinal strain rate analy- sis for both left and right ventricles in normal fetuses. The mean LV global peak systolic strain rate was −2.4/sec (standard deviation 1.2/sec) with a median of −1.9/sec (range −5.9/sec to −0.7/sec). The mean RV global peak sys- tolic strain rate was −1.9/sec (standard devi- ation 0.8/sec) with a median of −1.7/sec (range −3.8/sec to −0.5/sec). There was no statisti- cal difference between global strain rate and segmental strain rate measurements for either ventricle. Table III demonstrates the results of global and segmental longitudinal velocity analysis for both left and right ventricles in normal fetuses. The mean LV global peak systolic velocity was 1.6 cm/sec (standard deviation 0.6 cm/sec) with a median of 1.5 cm/sec (range 0.5–3.0 cm/sec). The mean RV global peak sys- tolic velocity was 1.6 cm/s (standard devia- tion 0.5 cm/sec) with a median of −1.6 cm/sec (range 0.8–2.3 cm/sec). In contrast to strain and strain rate measurements, the basal segmental 30 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 26, No. 1, 2009
  4. 4. FETAL GLOBAL LONGITUDINAL CARDIAC STRAIN AND STRAIN RATE Figure 1. Velocity vector tracing of the left ventricular endocardium (endo) in a normal fetus at 24 weeks of gestation with correspond- ing global and segmental strain curves. Global (average) peak sys- tolic strain curve is shown in black. Base left = septal base; mid-left = mid-septal; apex left = apical septal; apex right = apical free wall; mid- right = mid free wall; base right = basal free wall. velocities for both the left and right ventricles were significantly higher than the global ve- locity measurement, while the apical segmen- tal velocities were significantly lower than the global velocity measurement. Fetuses with congenital or functional heart disease demonstrated similar results, with no significant difference detected between global strain and global strain rate measurements compared to regional measurements. Segmen- tal velocities did differ, however, with the LV apical septal and apical free wall velocities sig- nificantly lower than the global velocity, and the basal free wall significantly higher. For the right ventricle, the mid-septal and apical sep- tal velocities were significantly lower, and the basal free wall significantly higher compared to the global RV peak velocity. TABLE I Ventricular Peak Global and Regional Strain Measurements in Normal Fetuses (n=33) LV Mean LV Median LV Range LV SD RV Mean RV Median RV Range RV SD Global strain −17.7 −16.6 −32.9 to −9.2 6.4 −18.0 −17.4 −33.4 to −6.7 6.4 Septal base −15.9 −15.4 −44.8 to −2 8.7 −17.3 −15.2 −34.3 to −5.6 7.9 Mid-septal −14.9 −13.4 −41.1 to −1.5 7.7 −17.4 −16.8 −31.5 to −6 6.7 Apical septal −18.5 −19.4 −37.9 to −4.7 8.5 −16.1 −15.0 −39.2 to −2.5 9.3 Apical free wall −19.3 −19.1 −41.9 to −2.6 9.5 −16.7 −15.5 39.2 to −1.5 10.1 Mid free wall −19.1 −19.0 −39 to −6.3 8.3 −19.4 −19.5 −33.1 to −8.2 7.0 Base free wall −17.8 −15.1 −37 to −5.7 9.4 −20.2 −18.2 −40 to −1.5 9.1 All values expressed as percent change in length. P > 0.05 for all regional strain measurements compared to global strain. LV = left ventricular; RV = right ventricular. Table IV demonstrates global peak longitu- dinal strain and strain rate measurements in fetuses with structural or functional heart dis- ease, compared with visually estimated func- tion and clinical outcome. There was an over- all trend toward lower global strain and strain rate compared to normal fetuses, but this was not uniform and varied depending upon disease state, with one fetus with aortic valve stenosis demonstrating global peak cardiac strain more than 1 standard deviation above the global peak systolic strain in normal fetuses. There was no correlation between calculated cardiac strain and strain rate and visually estimated ventric- ular function, although in one patient followed serially (chaotic atrial tachycardia [CAT 1]), the improvement in ventricular function matched an improvement from a low cardiac Vol. 26, No. 1, 2009 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 31
  5. 5. BARKER, ET AL. TABLE II Ventricular Peak Global and Regional Strain Rate Measurements in Normal Fetuses (n=22) LV Mean LV Median LV Range LV SD RV Mean RV Median RV Range RV SD Global strain rate −2.4 −1.9 −5.9 to −0.7 1.2 −1.9 −1.7 −3.8 to −0.5 0.8 Septal base −1.9 −1.7 −4.9 to −0.6 1.0 −1.9 −1.9 −4.1 to −0.9 0.8 Mid-septal −2.1 −1.9 −7.5 to −0.6 1.5 −1.9 −2.0 −3.8 to −0.9 0.8 Apical septal −2.7 −2.4 −8.2 to −0.6 1.7 −2.1 −1.8 −5.5 to −0.2 1.3 Apical free wall −2.8 −2.7 −5.7 to −0.2 1.5 −2.5 −1.9 −5.9 to −0.4 1.6 Mid free wall −2.4 −1.9 −5.7 to −0.7 1.4 −2.2 −2.3 −3.8 to −1 0.8 Base free wall −2.5 −1.9 −7.8 to −0.9 1.7 −2.3 −2.2 −4.6 to −0.9 1.1 All values expressed as rate of change in length (per second). P > 0.05 for all regional strain rate measurements compared to global strain rate. LV = left ventricular; RV = right ventricular. strain to closer to the normal value. Similarly, there was no correlation between calculated strain and strain rate and ultimate fetal out- come. Intraobserver variability ranged between 5– 12% for the left ventricle and 5–6% for the right ventricle. Interobserver variability ranged be- tween 10% for the left ventricle and 13% for the right ventricle. Discussion Myocardial strain and strain rate have been proposed as useful tools in the evaluation of car- diac mechanics. Myocardial strain and strain rate, being regional measurements, are rela- tively free of confounding factors such as car- diac translation, which may occur with respi- ration or motion of structures adjacent to the heart.10 The presence of multiple confounding variables such as fetal motion, high heart rates, and limited maternal transabdominal imaging TABLE III Ventricular Peak Global and Regional Velocity Measurements in Normal Fetuses (n=22) LV Mean LV Median LV Range LV SD RV Mean RV Median RV Range RV SD Global velocity 1.6 1.5 0.5–3.0 0.6 1.6 1.6 0.8–2.3 0.5 Septal base 2.1∗ 1.9 1.0–4.6 1.0 2.0∗ 2.1 0.8–3.1 0.6 Mid-septal 1.4 1.2 0.2–3.4 0.9 1.4 1.3 0.6–2.6 0.5 Apical septal 0.6∗ 0.6 0.0–1.5 0.4 0.8∗ 0.6 0.2–3.1 0.7 Apical free wall 1.0∗ 0.8 0.2–2.4 0.6 1.1∗ 1.1 0.1–2.4 0.7 Mid free wall 1.9 1.7 0.3–3.6 0.9 1.9 1.8 0.7–3.8 0.8 Base free wall 2.5∗ 2.5 0.8–4.9 1.0 2.6∗ 2.5 1.2–4.7 0.9 All values reported as cm/sec. ∗P < 0.05 for regional velocity measurement compared to global velocity measurement. LV = left ventricular; RV = right ventricular. windows therefore makes these new measure- ments appealing for assessment of fetal cardiac function. The majority of published studies have measured cardiac strain and strain rate us- ing tissue or color Doppler-derived velocities, although more recent speckle-tracking algo- rithms have permitted these measurements to be performed on two-dimensional data at ac- ceptably high frame rates.11 These measure- ments have been validated in vivo and in vitro for both tissue Doppler and two-dimensionally derived data, and have compared favorably to MRI-tagging techniques.7,10,11,13 While tissue Doppler has the advantage of less reliance on image quality and visual border detection, it has the inherent disadvantage of all Doppler technologies by being dependent on angle of in- sonation.5 This therefore limits the number of cardiac segments available for analysis to those parallel to the transducer beam, resulting in ex- clusion of the cardiac apex. 32 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 26, No. 1, 2009
  6. 6. FETAL GLOBAL LONGITUDINAL CARDIAC STRAIN AND STRAIN RATE TABLEIV SummaryofFetuseswithCongenitalorFunctionalHeartDisease Gest.AgeVisualVisual Diagnosis(weeks)LVStrainLVSRFunctionRVStrainRVSRFunctionClinicalOutcome SVT1,intermittent20−13.8−1.3Normal−9.3−1.1NormalTermdelivery,stablepostnatally HLHS1(mitralatresia,aortic atresia) 25N/AN/ANormal−13.5−1.3NormalTermdelivery,stables/ppalliation HLHS2(mitralstenosis,aortic stenosis) 23N/AN/ANormal−13.3−1.1NormalDeceasedinutero,unclearetiology SVT2,intermittent26−27.1−2.7Normal−27.6−3.2NormalTermdelivery,stablepostnatally TTTS1,donor(A), oligohydramnios 25−11.2−0.9Normal−16.8−1.4NormalPretermdelivery,stablepostnatally TTTS1,recipient(B), polyhydramnios 25−13.3−1Normal−13.3−1.3NormalPretermdelivery,stablepostnatally Ebstein’sanomalyoftricuspid valve 27−16.3−1.5Normal−18.5−1.9NormalHydropsat29weeks,deceased D-TGA/IVS33Inc.viewInc.viewNormal−11.3−0.9NormalTermdelivery TTTS2,recipient(A),pulm stenosis 29−13.6−1.1Normal−12.8−1.2NormalPretermdelivery,deceasedday2 TTTS2,donor(B),normal29−18.8−2.3Normal−25.6−3.5NormalPretermdelivery,survived VSD/AS/Coa31−20.5−2.3Normal−18.5−1.8NormalTermdelivery,stables/prepair CCTGA120−14.5−1.4Normal−10.6−0.8NormalTermdelivery,nointerventionneeded CCTGA138−13.9−0.9Normal−7.8−0.5Normal Aorticstenosis124−25.7−3.4Normal−21.1−2.2NormalTermdelivery Aorticstenosis128−28.1−3.6Normal−23.4−4.5Normals/pBAVday2,repeatBAV6weeks Aorticstenosis132−27.7−2.8Hypercontractile−27.3−3.9Normals/pRossprocedureat2months SVT3,earlyreturnofsinus rhythm 25−13.2−1.3Normal−15.5−1.4NormalHydrops SVT3,hydropsresolved33−16.6−1.5Normal−14.1−1.2NormalHydropsresolved,termdelivery CAT1,predominantlyin arrhythmia 33−10−1.3Mildlydecreased−11.7−1.2MildlydecreasedPretermdelivery,stablepostnatally CAT1,predominantlyinsinus rhythm 35−27.9−4Normal−16.5−1.9Normal Allstrainvaluesexpressedaspercentchangeinlength. Allstrainratevaluesexpressedasrateofchangeinlength(persecond). Gest.age=gestationalage;Inc.view=incompleteview;BAV=balloonaorticvalvuloplasty;CAT=chaoticatrialtachycardia;CCTGA={S,L,L}congenitally correctedtranspositionofthegreatarteries;D-TGA/IVS={S,D,D}transpositionofthegreatarterieswithintactventricularseptum;HLHS=hypoplasticleftheart syndrome;SVT=supraventriculartachycardia;TTTS=twin-twintransfusionsyndrome;VSD/AS/Coa=ventricularseptaldefectwithaorticstenosisandcoarctation oftheaorta;LV=leftventricular;RV=rightventricular;SR=strainrate. Vol. 26, No. 1, 2009 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 33
  7. 7. BARKER, ET AL. Dependency on angle of insonation is particu- larly problematic for fetal cardiology, given the extremely variable position of the fetus rela- tive to a transducer placed on the maternal ab- domen. In the first fetal study published using tissue Doppler to calculate fetal cardiac strain, this angle dependence limited analysis to only 75 of 120 fetuses (63%),8 although this im- proved in subsequent tissue/color Doppler stud- ies.4,9 A similar study reporting measurement of fetal tissue Doppler velocities, rather than myocardial strain, excluded 16% of potential subjects for similar reasons.17 In contrast, the two-dimensional feature- tracking program used in this study permit- ted the analysis of all visible ventricular seg- ments, independent of fetal position or angle of insonation. This resulted in only 1 ventricle out of a total of 104 ventricles being excluded for analysis due to limited views (<1% of at- tempted measurements). Additionally, the in- clusion of all six segments permitted the calcu- lation of global peak longitudinal systolic strain and strain rate as novel measurements of fetal ventricular function. This study demonstrates that the feature- based VVI software can be successfully ap- plied to fetal 2-dimensional echocardiographic datasets. This finding is similar to recently published fetal studies examining normal fe- tuses.2,3 Calculated global and regional peak systolic strain measurements for normal fe- tuses were similar for both the fetal left and right ventricles at approximately −18%, and −2.4 s−1 and −1.9 s−1 , respectively. These mea- surements are similar to those published from in vitro, adult, and fetal studies.3,6,8,10,13,18 However, calculated cardiac strain and strain rate were lower than two recently reported fe- tal and pediatric studies using tissue or color Doppler methods,4,6,8,10,13,19 with the exception of LV peak strain rate, which was similar to the reported pediatric values. While overall there has been a good reported correlation between tissue Doppler and the two commonly used feature-tracking algorithms, discrepancies be- tween these methods have also been recently reported that prevent the final definition of a normal range for these values in fetuses.20–23 Calculated myocardial velocities were lower than previously reported studies,2–4,17 although this study did not specifically analyze the veloc- ity at the atrioventricular annulus. It is not sur- prising that there was more variability between regional segments and global measurements of velocity, based upon fiber orientation vari- ation for both the left and right ventricles from base to apex.12 Previous studies have shown fe- tal myocardial velocity to vary with gestational age,2,4 consistent with fetal somatic growth, al- though the effect of gestational age was not as- sessed in this study. The finding that global measurements of peak longitudinal strain and strain rate are not significantly different from multiple seg- mental measurements suggests that global measurements may be a more useful tool to quantitate fetal cardiac function, and may be superior to tissue Doppler measurements. Specifically, global measurements based on two-dimensional datasets permit angle inde- pendent analysis and avoid any variation in the placement of the sample volumes or re- gions of interest in such a small structure as the fetal heart. In adult patients with systemic right ventricles, global measurements have been proposed as a method to avoid confound- ing wall motion abnormalities and local noise which may more greatly impact regional mea- surements.16 To this end, a lower global mea- surement may also provide a clue to look more closely at the individual segments for regional hypokinesis. For fetuses with congenital or functional heart disease, the global peak longitudinal strain and strain rate demonstrated a tendency toward lower values, although this was not uni- form as demonstrated by the fetus with aortic valve stenosis, the fetus with ventricular sep- tal defect/aortic stenosis and coarctation of the aorta, the fetus recovered from CAT 1, and the fetal right ventricle in the donor in one case of twin-twin transfusion syndrome (TTTS 2). It is possible to speculate that the increased strain and strain rate in these fetuses repre- sent myocardial compensation for the struc- tural heart disease (increased afterload in the case of aortic stenosis and ventricular septal de- fect/coarctation) and functional heart disease (increased cardiac output of the right ventri- cle in the donor twin). However, this theory does not fully explain the increase in strain and strain rate in the recovering fetus with ar- rhythmia, or the lower strain and strain rate throughout gestation of the fetus with con- genitally corrected transposition of the great arteries (CCTGA 1). Instead, these differences more likely underscore the limitations of our understanding of fetal cardiac adaptation to disease. The lack of significant correlation between calculated strain and strain rate, and visually 34 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. Vol. 26, No. 1, 2009
  8. 8. FETAL GLOBAL LONGITUDINAL CARDIAC STRAIN AND STRAIN RATE estimated cardiac function and outcomes in fe- tuses with heart disease further highlights our limitations in assessing fetal cardiac function and estimating prognosis. In the case of the two fetuses who died in utero, it is possible that they were well compensated at the time of the fetal study, and decompensated before the next visit. While the small number of abnormal fe- tuses and the variability in pathology limited our ability to analyze this group in more detail, the application of VVI to much larger groups of abnormal fetuses opens the field for further investigation. Limitations The small size of the current study prevents definition of normal values for fetuses at dif- ferent gestational ages, as well as prevents more detailed assessment of the relationship between calculated measurements and postna- tal outcome. RV strain and strain rate were cal- culated using a LV-derived six-segment model, which may not accurately reflect the more com- plex geometry of the right ventricle, but is similar in approach to previous studies using tissue Doppler from an apical view as the mea- surement tool. Circumferential and radial mea- surements were not analyzed in this study, and could provide useful comparisons to LV measurements. Unfortunately, compression of frame rate/time data limited the calculation of strain rate and velocity in a few fetuses, but this did not affect the strain measurement as strain is calculated directly from speckle motion by the VVI algorithm. Finally, the very nature of fetal imaging, due to the effect of fetal movement, size, position, and maternal factors complicate efforts to obtain two-dimensional datasets for analysis, although it is reassuring that ade- quate images with accurate border tracking could be obtained for all patients but one in this study. Conclusion Fetal global peak longitudinal strain, strain rate, and velocity can be successfully calculated independent of angle of insonation using VVI. Global peak longitudinal strain and strain rate do not differ from regional measurements. Pre- liminary experience suggests that normal fetal left and right ventricular global peak longitu- dinal strain and strain rate measurements are similar to those of the normal adult heart. This novel use of VVI is a promising tool for further investigation into fetal cardiac physiology. Acknowledgments: The authors are particularly in- debted to the sonographers and staff of the Duke University Pediatric Echo Laboratory for their assistance with image acquisition for this project. References 1. Kiserud T: Physiology of the fetal circulation. Semin Fetal Neonatal Med 2005;10:493–503. 2. Younoszai AK, Saudek DE, Emery SP, Thomas JD: Evaluation of myocardial mechanics in the fetus by velocity vector imaging. 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