Helena M. Gardiner

Arterial reactivity is significantly impaired in normotensive young adults after successful repair of aortic coarctation in childhood.

BACKGROUND Despite successful repair of coarctation of the aorta in childhood, adult survivors often have hypertension at rest or on exercise, and their life expectancy is shorter than normal because of premature coronary and cerebrovascular disease. This may be related to persistent structural and functional arterial abnormalities after surgery. METHODS AND RESULTS Using high-resolution ultrasound, we studied the right brachial arteries of 25 normotensive young adults who had undergone successful repair of coarctation in childhood (mean age at repair, 62 months; range, 0 to 167 months, including 8 patients operated on in infancy; mean age at study, 19 years; range, 14 to 27 years) and 50 age- and sex-matched control subjects. We assessed the degree of reactive hyperemia (RH) produced after distal cuff occlusion and release and the changes in arterial diameter in response to RH (with increased flow causing endothelium-dependent dilation) and to glyceryltrinitrate (GTN, an endothelium-independent dilator). The response of the right femoral artery to GTN was also measured in 12 coarctation subjects and 12 control subjects. Studies were performed 13.7 years (range, 7 to 21 years) after surgery. RH was significantly lower in coarctation subjects (343 +/- 130% versus 482 +/- 147%), as were endothelium-dependent dilation (3.8 +/- 3.3% versus 8.8 +/- 3.6%) and GTN response (13.3 +/- 6.0% versus 20.5 +/- 6.1%) (P < .001 for each), reflecting abnormal dilatory capacity in both the resistance and conduit arteries. In contrast, GTN-induced dilation in the femoral arteries was similar to that in control subjects (9.5 +/- 2.6% versus 10.1 +/- 4.1%, P = .70). On multivariate analysis, GTN response and systolic blood pressure at peak exercise were inversely correlated (r = -.52, P = .04). Vascular responses were not related to the age at repair. CONCLUSIONS Despite successful repair of coarctation in childhood, arterial dilation is significantly impaired in the precoarctation vascular bed of healthy young adults. This may be an important contributor to exercise-related hypertension and late morbidity or mortality.

Influence of twin-twin transfusion syndrome on fetal cardiovascular structure and function: prospective case–control study of 136 monochorionic twin pregnancies

Objective: To test the hypothesis that identical twins show no inter-twin differences in cardiovascular structure or physiology in fetal life unless there has been twin-twin transfusion syndrome. Design: Unselected prospective case–control observational study of fetoplacental haemodynamics including echocardiography at a median of 24 (16.7 to 32.3) weeks, with postnatal confirmation of congenital heart disease or normality. Setting: Fetal medicine unit. Patients: 136 women with monochorionic diamniotic twin pregnancies, of which 47 fetal twin pairs (35%) had twin-twin transfusion syndrome. Results: There were no haemodynamic differences between the bigger fetus (twin 1) and the smaller co-twin (twin 2) in uncomplicated monochorionic diamniotic pairs. In twin-twin transfusion syndrome, recipient fetuses had increased aortic and pulmonary velocities compared with their donor co-twins (mean (SD): 0.73 (0.23) m/s and 0.63 (0.14) m/s), respectively, v 0.53 (0.16) m/s and 0.48 (0.10) m/s in donor twins; p = 0.003 (aortic) and < 0.0001 (pulmonary)), and also in comparison with twin 1 and twin 2. The overall prevalence of congenital heart disease was increased above that in singletons (3.8% v 0.56%; 6.9% in twin-twin transfusion v 2.3% in uncomplicated monochorionic diamniotic twins), with inter-twin discordance for defects. The prevalence in recipient twins was 11.9% (p = 0.014 v uncomplicated control twins). Conclusions: Fetuses with an identical genome but no circulatory imbalance have similar cardiovascular physiology but discordant phenotypic expression of congenital heart disease. The high prevalence of congenital heart disease in monochorionic diamniotic twins merits detailed fetal echocardiography.

Fetal origins of reduced arterial distensibility in the donor twin in twin-twin transfusion syndrome

Twin-twin transfusion syndrome permits investigation of vascular programming independent of genetic influence. Arterial distensibiity was lower in the donor twin during infancy, implying the intrauterine vascular remodelling might result in raised cardiac afterload and could influence later cardiovascular health.

Non-invasive fetal electrocardiography in singleton and multiple pregnancies

Objectives To document the duration of fetal cardiac time intervals in uncomplicated singleton pregnancies using a novel non‐invasive fetal electrocardiography (fECG) system and to demonstrate this techniques ability to acquire recordings in twin and triplet pregnancies.

Isolated Atrioventricular Block in the Fetus A Retrospective, Multinational, Multicenter Study of 175 Patients

Background— Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome. Methods and Results— We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000–2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1–21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age <20 weeks, ventricular rate ≤50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4±2.9 versus 24.9±4.9 weeks; P =0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy. Conclusions— Risk factors associated with a poor outcome were gestation <20 weeks, ventricular rate ≤50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen. # Clinical Perspective {#article-title-22}Background— Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome. Methods and Results— We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000–2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1–21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age <20 weeks, ventricular rate ⩽50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4±2.9 versus 24.9±4.9 weeks; P=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy. Conclusions— Risk factors associated with a poor outcome were gestation <20 weeks, ventricular rate ⩽50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.

Morphological and Physiological Predictors of Fetal Aortic Coarctation

Background— Prenatal diagnosis of aortic coarctation suffers from high false-negative rates at screening and poor specificity. Methods and Results— This retrospective study tested the applicability of published aortic arch and ductal Z scores (measured just before the descending aorta in the 3-vessel and tracheal view) and their ratio on 200 consecutive normal controls at a median of 22±0 gestational weeks (range, 15±4 to 38±4 weeks). Second, this study tested the ability of serial Z scores to distinguish fetuses with coarctation within a cohort with ventricular and/or great arterial disproportion detected at screening or fetal echocardiography. Third, it evaluated the diagnostic significance of associated cardiac lesions, coarctation shelf, and isthmal flow disturbance. We studied 44 fetuses with suspected coarctation at 24±0 weeks (range, 17±3 to 37±4 weeks). Receiver-operating characteristic curves were created. Logistic regression tested the association between z scores, additional cardiac diagnoses, and coarctation. Good separation was found of isthmal Z scores for cases requiring surgery from controls and false-positive cases, and receiver-operating characteristic curves showed an excellent area under the curve for isthmal Z score (0.963) and isthmal-to-ductal ratio (0.969). Serial isthmal Z scores improved to >−2 in suspected cases with normal outcomes; those requiring surveillance or surgery remained <−2. Minor lesions did not increase the diagnostic specificity of coarctation, but isthmal flow disturbance increased the odds ratio of true coarctation versus arch hypoplasia 16-fold. Conclusions— Isthmal Z scores and isthmal-to-ductal ratio are sensitive indicators of fetal coarctation. Serial measurements and abnormal isthmal flow patterns improve diagnostic specificity and may reduce false positives.

Twin-twin transfusion syndrome: the influence of intrauterine laser photocoagulation on arterial distensibility in childhood.

Background—In twin-twin transfusion syndrome (TTTS), the donor and recipient fetus are exposed to differing volume loads and show discordant intertwin vascular compliance in childhood despite identical genotype. We hypothesized that discordance is prevented by intrauterine endoscopic laser ablation of placental anastomoses, which abolishes intertwin transfusion. We tested this by examining pulse wave velocity (PWV) in brachial arteries of twin survivors of TTTS treated with and without laser therapy. Methods and Results—One hundred children (50 twin pairs, 27 with TTTS) were studied. Group 1 comprised 14 monochorionic (MC) twin pairs with TTTS treated symptomatically; group 2 comprised 13 MC twin pairs with TTTS treated by laser. The control groups comprised 12 MC twin pairs without TTTS (group 3) and 11 dichorionic twin pairs (group 4). Fetal cardiovascular data, predictive factors for, and duration of TTTS and cord blood were collected prospectively. We measured blood pressure and PWV photoplethysmographically at a median corrected postnatal age of 11 months (range, 1 week to 66 months). Both TTTS groups showed marked intertwin PWV discordance, unlike MCDA control subjects. The PWV discordance seen in laser treated twin pairs resembled that of dichorionic control subjects (heavier individual with higher PWV), whereas group 1 showed the opposite (negative) intertwin discordance (ANOVA F (1,45)=4.5, P =0.04). No significant differences in blood pressure or intrauterine growth were observed between TTTS groups. Conclusions—Vascular programming is evident in monozygotic twins with intertwin transfusion and is altered but not abolished by intrauterine therapy to resemble that seen in dichorionic twins.

Temporal and Spatial Performance of Vector Velocity Imaging in the Human Fetal Heart

To assess the spatial and temporal performance of fetal myocardial speckle tracking, using high‐frame‐rate (HFR) storing and Lagrangian strain analysis.

Response of the fetal heart to changes in load: from hyperplasia to heart failure.

The fetal circulation works in parallel with the dominant right ventricle, ejecting approximately 60% of the combined ventricular output. Three important communications exist between the two circulations (oval foramen and the arterial and venous ducts) that influence loading conditions. In particular, the determinants of fetal left ventricular filling differ considerably from those seen in the adult heart. Pulmonary venous return contributes only a small proportion to left ventricular preload because of the relatively low pulmonary blood flow in fetal life (rising from an estimated 11% to 25% of right ventricular output by the third trimester).1 Left ventricular filling depends predominantly on patency of the oval foramen to allow the relatively oxygen-rich blood returning from the placental circulation, via the umbilical vein and venous duct, to stream through the right atrium and enter the left side of the heart.2 The right ventricle fills from mostly upper body systemic venous return and the majority of its output is diverted away from the pulmonary circulation, via the arterial duct, to the descending aorta and thence to the placenta via the umbilical arteries. Hence the fetal right ventricle pumps against the systemic pressures of the lower fetal body and placental impedance, while the left ventricle ejects against the relatively high impedance of the fetal brain and upper body. Not surprisingly, ventricular loading is affected by the maturation of structures such as the placenta and changes in the impedance of the cerebral and placental vascular beds in response to hypoxaemia, as well as circulatory adaptations made by the fetus in response to intracardiac malformations. Loading patterns alter throughout gestation; the ventricular pressure–volume loops of the chick embryo show an active response to increasing preload as the early myocardium organises.3 Mid trimester studies in the human fetus demonstrate the importance of trophoblastic invasion …

Fetal ECG: A Novel Predictor of Atrioventricular Block in Anti-Ro Positive Pregnancies

Objective: Approximately 2.8% of pregnancies are Ro/La antibody positive. 3–15% of fetuses develop complete heart block (CHB). First-degree atrioventricular heart block (1° AVB) is reported in a third of Ro/La fetuses but as most have a normal postnatal ECG this may reflect inadequacies of Doppler measurement techniques. Methods: Comparison was made between mechanical (mPR) and electrical (ePR) intervals obtained prospectively using Doppler and non-invasive fetal ECG (fECG) in 52 consecutive Ro/La pregnancies in 46 women carrying 54 fetuses in an observational study at a fetal medicine unit. 121 mPR and 37 ePR intervals were recorded in 49 Ro/La fetuses. Five were referred with CHB and excluded. ePR was measured successfully in 35/37 (94%) and mPR was measured in all cases. 1° AVB was defined as PR >95% CI. Logistic regression predicted abnormal final fetal rhythm from first mPR or ePR. Results: The ePR model gave 66.7% sensitivity (6 of 8 final abnormal fetal rhythm cases were predicted correctly in fetuses >20 weeks) and 96.2% specificity. mPR gave 44.4% sensitivity (4 of 9 cases) and 88.5% specificity. Z scores for ePR (zPR) were calculated from 199 normal fetuses. The area under the receiver operator characteristic (ROC) curve was 0.88 (95% CI, 0.754 to 1.007). A cut-off of 1.65 gave a sensitivity of 87.5% and specificity of 95% for those with prolonged and normal ePR intervals, respectively. Conclusion: zPR is better than mPR at differentiating between normal and prolonged PR intervals, suggesting that fECG is the diagnostic tool of choice to investigate the natural history and therapy of conduction abnormalities in Ro/La pregnancies.