Speckle tracking-derived myocardial tissue deformation imaging in twin-twin transfusion syndrome: differences in strain and strain rate between donor and recipient twins.

OBJECTIVES: Twin-twin transfusion syndrome (TTTS) is a complex disorder with altered cardiovascular loading conditions that affects both donors and recipients. Myocardial tissue deformation analysis using vector velocity imaging is an angle-independent, speckle-tracking technique which can assess myocardial mechanics and may provide insight into cardiac dysfunction in TTTS. METHODS: Digital dynamic two-dimensional four-chamber views were interrogated offline. Images were acquired utilizing standard video frame rates (30 frames/s). The global longitudinal strain, systolic strain rate, and diastolic strain rate were measured in the left (LV) and right ventricles (RV) of 25 fetal pairs with TTTS and compared to 25 gestational age-matched normal controls. Pulsatility indices for the umbilical artery and middle cerebral artery were measured. RESULTS: The gestational age at evaluation was 20.5 ± 1.3 weeks. The donor LV systolic strain rate was higher, while the donor RV diastolic strain rate was significantly lower, than control values. The recipient longitudinal strain, systolic strain rate, and diastolic strain rate were significantly lower for both LV and RV in comparison to controls. The donor umbilical artery pulsatility index was higher than control values (1.92 ± 0.45 vs. 1.41 ± 0.25, p < 0.001), while the donor middle cerebral artery pulsatility index was lower (1.46 ± 0.28 vs. 1.87 ± 0.21). Recipient umbilical artery and middle cerebral artery pulsatility indices were no different than control values. CONCLUSIONS: In TTTS, both the donor and the recipient exhibit abnormalities of myocardial tissue deformation with ventricle-specific changes evident based on loading conditions. Donor LV systolic function is hyperdynamic due to hypovolemia and selective ejection into a low-resistance cerebrovascular circuit while the donor RV selectively ejects into a high-resistance placental circuit. Recipient RV and LV are both globally depressed with systolic and diastolic dysfunction. Further prospective validation of our findings using high frame rate analysis is indicated.

Homozygous missense N629D hERG (KCNH2) potassium channel mutation causes developmental defects in the right ventricle and its outflow tract and embryonic lethality.

Loss-of-function mutations in the human ERG1 potassium channel (hERG1) frequently underlie the long QT2 (LQT2) syndrome. The role of the ERG potassium channel in cardiac development was elaborated in an in vivo model of a homozygous, loss-of-function LQT2 syndrome mutation. The hERG N629D mutation was introduced into the orthologous mouse gene, mERG, by homologous recombination in mouse embryonic stem cells. Intact homozygous embryos showed abrupt cessation of the heart beat. N629D/N629D embryos die in utero by embryonic day 11.5. Their developmental defects include altered looping architecture, poorly developed bulbus cordis, and distorted aortic sac and branchial arches. N629D/N629D myocytes from embryonic day 9.5 embryos manifested complete loss of I(Kr) function, depolarized resting potential, prolonged action potential duration (LQT), failure to repolarize, and propensity to oscillatory arrhythmias. N629D/N629D myocytes manifest calcium oscillations and increased sarcoplasmic reticulum Ca(+2) content. Although the N629D/N629D protein is synthesized, it is mainly located intracellularly, whereas +/+ mERG protein is mainly in plasmalemma. N629D/N629D embryos show robust apoptosis in craniofacial regions, particularly in the first branchial arch and, to a lesser extent, in the cardiac outflow tract. Because deletion of Hand2 produces apoptosis, in similar regions and with a similar final developmental phenotype, Hand2 expression was evaluated. Robust decrease in Hand2 expression was observed in the secondary heart field in N629D/N629D embryos. In conclusion, loss of I(Kr) function in N629D/N629D cardiovascular system leads to defects in cardiac ontogeny in the first branchial arch, outflow tract, and the right ventricle.

Fetal Cardiac Function in Maternal Diabetes: A Conventional and Speckle-Tracking Echocardiographic Study.

BACKGROUND: Intrauterine exposure to a diabetic environment is associated with adverse fetal myocardial remodeling. The aim of this study was to assess the biventricular systolic and diastolic function of fetuses exposed to maternal diabetes (MD) compared with control subjects, using a comprehensive cardiac functional assessment and exploring the role of speckle-tracking to assess myocardial deformation. The authors hypothesized that fetuses exposed to MD present signs of biventricular dysfunction, which can be detected by deformation analysis. METHODS: A cross-sectional study was conducted in 129 fetuses with structurally normal hearts, including 76 fetuses of mothers with diabetes and 53 of mothers without diabetes. Maternal baseline characteristics, standard fetoplacental Doppler indices, and conventional echocardiographic and myocardial deformation parameters were prospectively collected at 30 to 33 weeks of gestation. RESULTS: Fetuses of mothers with diabetes had a significantly thicker interventricular septum compared with control subjects (median, 4.25 mm [interquartile range (IQR), 3.87-4.50 mm] vs 3.67 mm [IQR, 3.40-3.93 mm), P < .001), but no effect modification was demonstrated on myocardial deformation analysis. No significant differences were found in conventional systolic and diastolic functional parameters for the left ventricle and right ventricle, except for lower left ventricular cardiac output in the MD group (median, 320 mL/min [IQR, 269-377 mL/min] vs 365 mL/min [IQR, 311-422 mL/min], P < .05]. Deformation analysis demonstrated a significantly lower early diastolic strain rate (SRe) and late diastolic strain rate (SRa) for both ventricles in the MD group (left ventricle: SRe 1.85 ± 0.72 vs 2.26 ± 0.68 sec-1, SRa 1.50 ± 0.52 vs 1.78 ± 0.57 sec-1; right ventricle: SRe 1.57 ± 0.73 vs 1.97 ± 0.73 sec-1, SRa 2 ± 0.77 vs 1.68 ± 0.79 sec-1; P < .05), suggesting biventricular diastolic impairment. Additionally, the right ventricle presented a lower global longitudinal strain in the study group (-13.67 ± 4.18% vs -15.52 ± 3.86%, P < .05). Multivariate analysis revealed that maternal age is an independent predictor of left and right ventricular global longitudinal strain (P < .05), with a significant effect only in MD after group stratification. CONCLUSIONS: Fetuses of mothers with diabetes present signs of biventricular diastolic dysfunction and right ventricular systolic dysfunction by deformation analysis in the third trimester of pregnancy. They may represent a special indication group for functional cardiac assessment, independently of septal hypertrophy. Two-dimensional speckle-tracking could offer an additional benefit over conventional echocardiography to detect subclinical unfavorable changes in myocardial function in this population.

Effect of Hypoxemia on Fetal Ventricular Deformation in a Chronically Instrumented Sheep Model.

We hypothesized that in near-term sheep fetuses, hypoxemia changes myocardial function as reflected in altered ventricular deformation on speckle-tracking echocardiography. Fetuses in 21 pregnant sheep were instrumented. After 4 d of recovery, fetal cardiac function was assessed by echocardiography at baseline, after 30 and 120 min of induced fetal hypoxemia and after its reversal. Left (LV) and right (RV) ventricular cardiac output and myocardial strain were measured. Baseline mean (standard deviation [SD]) LV and RV global longitudinal strains were -18.7% (3.8) and -14.3% (5.3). Baseline RV global longitudinal and circumferential deformations were less compared with those of the left ventricle (p = 0.016 and p < 0.005). LV, but not RV, global longitudinal strain was decreased (p = 0.003) compared with baseline with hypoxemia. Circumferential and radial strains did not exhibit significant changes. In the near-term sheep fetus, LV global longitudinal and circumferential strains are more negative than RV strains. Acute hypoxemia leads to LV rather than RV dysfunction as reflected by decreased deformation.

Fetal sheep left ventricle is more sensitive than right ventricle to progressively worsening hypoxemia and acidemia.

OBJECTIVE: In a sheep model we tested the hypothesis that the fetal left ventricle is less tolerant to worsening acidemia than the right ventricle. STUDY DESIGN: At 106-124/145 days of gestation, 12 fetuses were instrumented. After a 4-day recovery, placental vascular resistance was increased by fetal angiotensin (AT) II infusion. After a 2h ATII infusion, to further deteriorate fetal oxygenation, maternal hypoxemia was induced. Fetal cardiac function and hemodynamics were assessed by tissue Doppler imaging (TDI) and pulsed Doppler imaging. Ultrasonography was performed at baseline, at 1 and 2h after the beginning of ATII infusion and during the ATII+hypoxemia phase. RESULTS: Fetal pH and pO2 decreased significantly and progressively during the experiment. Left ventricular TDI-derived isovolumic relaxation velocity (IVRV) was lower during ATII 2h and ATII+hypoxemia phases than at baseline. The IVRV deceleration was significantly less during the ATII+hypoxemia phase than at baseline. Right ventricular IVRV was significantly lower during the ATII+hypoxemia phase than at baseline. IVRV deceleration did not change. Only left ventricular IVRV deceleration correlated with fetal pO2 (R=0.36, p<0.05). Fetal right and left ventricular cardiac outputs, as well as umbilical artery, aortic isthmus and ductus venosus pulsatility indices remained unchanged during the experiment. CONCLUSION: Our results show that signs of cardiac dysfunction develop earlier in the left ventricle than in the right ventricle. The fetal left ventricle seems to be more sensitive to progressively worsening hypoxemia and acidemia than the right ventricle.

Right ventricular function in the human fetus.

Fetal RV function is critical for survival and normal cardiovascular development. Doppler can be used to assess function. Combined with wise use of imaging techniques, the cause of abnormalities can be assessed. Both congenital heart defects and other cardiovascular defects can lead to hydrops and death. Serial semi-quantitation of fetal heart failure can be done with a Cardiovascular Profile score.