Prenatal Diagnosis Improves the Postnatal Cardiac Function in a Population-Based Cohort of Infants with Hypoplastic Left Heart Syndrome


Prenatal diagnosis of hypoplastic left heart syndrome (HLHS) enables planning of perinatal care and is known to be associated with more stable preoperative hemodynamics. The impact on postnatal myocardial function is poorly known. The aim of this study was to determine the impact of prenatal diagnosis of HLHS on postnatal myocardial function.


A consecutively encountered cohort of 66 infants with HLHS born between 2003 and 2010 in Finland was retrospectively reviewed. Twenty-five infants had prenatal diagnoses. Postnatal global and segmental right ventricular fractional area change, strain rate, and myocardial velocity were analyzed from the apical four-chamber view using Velocity Vector Imaging. Preoperative hemodynamic status and end-organ damage measurements were the lowest arterial pH, highest lactate, alanine aminotransferase, and creatinine. Early mortality was studied until 30 days after Norwood procedure.


Prenatally diagnosed infants had better cardiac function (fractional area change, 27.9 ± 7.4% vs 21.1 ± 6.3%, P = .0004; strain rate, 1.1 ± 0.6/1.3 ± 1.0 vs 0.7 ± 0.2/0.7 ± 0.3 1/sec, P = .004/.003; myocardial velocity, 1.6 ± 0.6/2.0 ± 1.1 vs 1.3 ± 0.4/1.4 ± 0.4 cm/sec, P = .0035/.0009). Mechanical dyssynchrony was similar in both groups ( P > .30). Infants diagnosed prenatally had less acidosis (pH = 7.30 vs 7.25, P = .005) and end-organ dysfunction (alanine aminotransferase, 33 ± 38 vs 139 ± 174 U/L, P = .0001; creatinine, 78 ± 18 vs 81 ± 44 mmol/L, P = .05). No deaths occurred among the prenatally diagnosed infants, but four deaths were recorded among postnatally diagnosed infants ( P = .15).


A prenatal diagnosis of HLHS is associated with improved postnatal right ventricular function, reduced metabolic acidosis, and end-organ dysfunction.

Hypoplastic left heart syndrome (HLHS) is characterized by a small left ventricle incapable of maintaining systemic cardiac output. HLHS can be identified using four-chamber screening and is one of the most common severe congenital cardiac defects diagnosed prenatally. Prenatal diagnosis of this disorder enables planning for birth with optimized postnatal stabilization of these affected infants. Prenatally diagnosed infants have been shown to have superior postnatal hemodynamics and less severe acidosis and organ failure compared with postnatally diagnosed infants. Subjective observations have also suggested that a prenatal diagnosis might improve myocardial function in the neonatal period, but no quantitative evaluation of right ventricular (RV) function in this patient population has been reported thus far.

Vector Velocity Imaging (VVI; Siemens Healthcare, Erlangen, Germany) measures myocardial velocities, myocardial deformation, and mechanical synchrony. VVI is independent of the angle of insonation and the geometry of the ventricle and is an important tool for measuring both myocardial function and mechanical synchrony in patients with HLHS. The accuracy of subjective evaluation of myocardial function in comparison with magnetic resonance imaging has been poor in patients with HLHS.

The aim of the present study was to determine whether prenatal diagnosis of HLHS improves postnatal quantitative global or segmental RV myocardial function of affected infants and whether prenatal diagnosis has any impact on early (<30-day) mortality outcomes after a Norwood operation in a country (Finland) where all cardiac surgeries have been centralized.


This retrospective, population-based study involved a cohort of 66 consecutive infants with HLHS born in Finland between January 2003 and December 2010. These patients were divided into two groups on the basis of whether they had prenatal or postnatal diagnoses of HLHS. All the infants in our study cohort who had prenatal diagnosis were delivered at the University Hospital of Helsinki. Prostaglandin infusion was started immediately after birth before admission to the intensive care unit. Respiratory support and inotropes were not routinely started. Infants who had not received intrauterine diagnoses were born in delivery hospitals around Finland and were transported to Helsinki University Hospital after diagnosis and stabilization. The mean transportation distance from delivery hospital to operative center was 225 ± 202 km.

Patients with major extracardiac defects or chromosomal abnormalities were excluded from our study cohort. None of the infants had significant atrial septal restriction needing postnatal septostomy. Assessment of restrictive atrial septum was based on pulmonary venous Doppler prenatally and anatomy of the atrial septum and clinical picture postnatally. Clinical data were collected from medical records. Preoperative hemodynamic status was assessed by measurement of the lowest arterial pH and highest lactate level. Kidney function was assessed by assessing the highest preoperative creatinine and liver function through the maximum alanine aminotransferase concentrations. The study was approved by the hospital research committee.

Cardiac Evaluations

Cardiac function was retrospectively evaluated in 59 infants using an Xcelera (Philips Medical Systems, Andover, MA) database of ultrasound images. The first detailed diagnostic echocardiography was performed immediately after the infant was admitted to our unit. The images analyzed in this study were obtained later at the time of preoperative functional assessment, performed at a median age of 1 day (range, 0–12 days) for prenatally diagnosed infants and 2 days (range, 0–8 days) for postnatally diagnosed infants ( P = .30). These images were recorded in accordance with a standardized ultrasound protocol at the time of the preoperative evaluation after stabilization at our institution. Seven infants were excluded from the VVI analysis because their postnatal cardiac ultrasound was missing or of insufficient quality for VVI analysis: one from the prenatal and six from the postnatal diagnosis group ( P = .24). Aortic, pulmonary, mitral, and tricuspid valve dimensions were measured by one of the authors (H.K.M.) according to published recommendations. The severity of tricuspid and pulmonary valve insufficiency was classified as hemodynamically significant (moderate or severe) or insignificant (none, trivial, or mild), taking into account the vena contracta width and the area of color Doppler flow. All infants were divided into three categories according to the morphology of the mitral and aortic valves: mitral and aortic stenosis (MS/AS), mitral stenosis and aortic atresia (MS/AA), and mitral and aortic atresia (MA/AA). For functional analysis, cardiac ultrasound data were transferred in a standard Digital Imaging and Communications in Medicine format to the VVI analysis program (syngo USWP 3.0; Siemens Healthcare). Originally, the images were acquired at a frame rate of 30 to 95 Hz, although digital storage reduces the effective frame rate to 30 Hz. The data were then stored in a research archive with code numbers. All cardiac functional analyses were performed by one of the authors (H.K.M.), who was blinded to the clinical presentation and outcomes of the patients with HLHS.

RV fractional area change (FAC) values, global and segmental myocardial velocities and strain rates, and mechanical synchrony were analyzed from the apical four-chamber view using the VVI technique. Manual tracing of the RV subendocardial surface was performed in a single still frame in midsystole. Tracing began at the edge of the tricuspid 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 tricuspid valve annulus. Velocity vectors were then automatically calculated for each frame of the cardiac cycle by the VVI algorithm and displayed for the complete loop ( Figure 1 ). The software divided the right ventricle automatically into six segments for regional and synchrony analysis. Tracings were accepted only if the subendocardial border was correctly followed throughout the whole cardiac cycle. If necessary, individual regions of the border were adjusted until the border was correctly tracked for each frame. Left ventricular end-diastolic volume was estimated from the apical four-chamber view using the Auto Left Heart program (syngo USWP 3.0). To minimize intraobserver variability, all measurements were repeated three times, and the mean value was used in the analyses. Mechanical synchrony was measured as the time to peak strain rate and velocity values from the beginning of the QRS complex in all six segments. The degree of mechanical dyssynchrony was quantified as the standard deviation of these values among six different cardiac segments. For intraobserver and interobserver variability, 10 randomly selected studies were analyzed twice by the same investigator (H.K.M.) 4 weeks later and once by another investigator (T.H.O.).

Figure 1

(A) Tracing of velocity vectors during systole. Segmental myocardial velocities (B) and strain rate (C) among the six segments of the right ventricle analyzed ( color coded ) are displayed as a function of time. In the tables, peak longitudinal velocity and strain rate are given for six segments of the right ventricle and the total average value.

Statistical Analysis

Clinical demographics and global cardiac functional data for the study groups were compared using t tests or Mann-Whitney U test for continuous parameters, Cochran-Mantel-Haenszel tests for noncontinuous parameters, and Fisher’s exact tests or Pearson’s χ 2 tests for frequencies. Segmental cardiac analyses were evaluated statistically by repeated-measures analysis of variance using the segment as the repeating factor. In case of a significant segment–to–study group interaction, post hoc analyses were performed within segments using Bonferroni-corrected t tests between study groups. Logarithmic transformation was used to normalize skewed distributions for the t tests and repeated-measures analysis of variance models. Correlations ( R values) were calculated using Pearson’s correlation coefficient for normally distributed data and Spearman’s rank correlation coefficient for abnormally distributed data. Intraobserver and interobserver reproducibility was assessed for 10 randomly selected patients for FAC, velocities, and strain rate. Reproducibility was assessed from the corresponding repeated measures using intraclass correlation coefficients with 95% confidence intervals. For global variables, reproducibility was good (intraclass correlation coefficient > 0.83) ( Figure 2 ). A P value < .05 was used to define significance. SPSS for Windows version 19.0 (SPSS, Inc./IBM Corporation, Somers, NY) and SAS version 9.2 (SAS Institute Inc., Cary, NC) were used to perform statistical analyses.

Figure 2

Intraobserver and interobserver reproducibility of FAC, velocities, and strain rate represented as intraclass correlation coefficients (ICCs) and 95% confidence intervals (CIs).


Of the 66 infants with HLHS, 25 (38%) had received prenatal diagnoses, and 41 (62%) were postnatally diagnosed. The prevalence of a prenatal diagnosis of HLHS increased during the study era (from 22% to 75%). There were no significant differences between the clinical demographics of the study groups and the morphology of HLHS ( Table 1 ). For the postnatally diagnosed infants, the median time lag from delivery to diagnosis was 1 day (range, 0–7 days). Oxygen saturation screening for the detection of cardiac defects was started after 2008 at most delivery hospitals in Finland. Early oxygen saturation screening was performed for eight postnatally diagnosed infants. Postductal saturation in oxygen saturation screening was initially normal (>95%) for two infants (25%) with postnatal diagnoses of HLHS, and in both of these neonates, saturation became abnormal (<95%) before discharge. The majority, 33 of 41 (80%), of postnatally diagnosed infants did not undergo oxygen saturation screening. Five had delayed diagnoses >72 hours after birth. There was no delayed diagnosis among infants with oxygen saturation screening.

Table 1

Clinical characteristics of the 66 patients with HLHS divided into two study groups on the basis of whether a prenatal diagnosis had occurred

Variable Prenatal diagnosis ( n = 25) Postnatal diagnosis ( n = 41) P
Birth data
Maternal age (y) 29 (22–36) 27 (20–40) .70
Gestational weeks at birth (wk) 39 (37–41) 40 (36–42) .80
Male (%) 13 (52%) 25 (61%) .50
Birth weight (g) 3,440 (2,690–4,300) 3,520 (2,220–4,572) .70
Apgar score (points) 9 (7–9) 9 (6–10) .70
Morphology group .20
MS/AS 8 (32%) 19 (48%)
MS/AA 5 (20%) 10 (25%)
MA/AA 12 (48%) 11 (28%)
Laboratory values
Lowest arterial pH 7.30 ± 0.04 7.25 ± 0.09 .005
Highest lactate (mmol/L) 3.5 ± 1.9 3.8 ± 3.9 .10
Highest creatinine (μmol/L) 78 ± 18 81 ± 44 .05
Highest alanine aminotransferase (U/L) 33 ± 38 139 ± 174 .0001
Operative management
Blalock-Taussig shunt (%) 7 (28%) 16 (49%) .40
Sano shunt (%) 18 (72%) 34 (51%) .40
Operative age (d) 6 (3–9) 7 (3–17) .008
Early (<30-d) postoperative mortality 0 (0%) 4 (10%) .15

Data are expressed as median (range), number (percentage), or mean ± SD. P values are from t tests except as indicated.

Fisher’s exact test.

Cochran-Mantel-Haenszel test.

Pearson’s χ 2 test.

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Jun 1, 2018 | Posted by in CARDIOLOGY | Comments Off on Prenatal Diagnosis Improves the Postnatal Cardiac Function in a Population-Based Cohort of Infants with Hypoplastic Left Heart Syndrome

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