Single Ventricular Circulation Research Articles

Two-dimensional speckle tracking echocardiography in fetuses with critical aortic stenosis before and after fetal aortic valvuloplasty.

Critical aortic stenosis (AS) in fetuses may progress to hypoplastic left heart syndrome (HLHS) with need for postnatal single ventricular (SV) palliation. Fetal aortic valvuloplasty (FAV) is performed to achieve postnatal biventricular (BV) circulation. However, the impact of FAV on fetal myocardial function is difficult to measure. Prediction of postnatal circulatory status and, therefore, counseling is challenging. Retrospective study of fetuses with critical AS who underwent FAV. Global Longitudinal Peak Systolic Strain (GLPSS) of the left ventricle (LV) and right ventricle (RV) were retrospectively analyzed before and after intervention. Fisher's Exact Test and Mann-Whitney-U Test were used for univariant statistical analysis. 23 fetuses with critical AS were included. After intervention fetuses demonstrated more negative LV-GLPSS mean values post- vs. pre-intervention (-5.36% vs. -1.57%; p < 0.05). RV-GLPSS was decreased in all fetuses, there was no peri-interventional change. 20 fetuses were born alive. Postnatally, 10 had BV and 10 SV circulation. Improved post-interventional LV-GLPSS strain values correlated with BV outcome (p < 0.05). Pre-interventional continuous LV-GLPSS values correlated with postnatal SV vs. BV outcome (p < 0.05). In some fetuses, LV myocardial function assessed by speckle tracking echocardiography (STE) improves after FAV. Improved post-interventional LV-GLPSS correlates with biventricular postnatal outcome. Furthermore, pre-interventional LV- and RV-GLPSS correlate with postnatal outcome. Further studies are needed to asses, if pre-interventional STE parameters might predict which fetuses will benefit from FAV with postnatal BV circulation.

Late-gestation prediction of outcome in tricuspid valve dysplasia and Ebstein's anomaly using fetal tricuspid regurgitation waveform analysis.

To investigate the criteria, based on fetal TR waveforms in late gestation, to predict biventricular circulation (BV) after birth in cases of tricuspid valve dysplasia (TVD) or Ebstein's anomaly diagnosed during the fetal period. We included 35 consecutive cases diagnosed with TVD or Ebstein's anomaly during the fetal period between January 2008 and December 2021 at Kanagawa Children's Medical Center, Kanagawa, Japan. The maximum velocity and change in pressure over time of tricuspid regurgitation (TR) jet (dP/dt), estimated using TR waveforms obtained during the late-gestation period (gestational age ≥ 28 weeks), were collected from patient records. dP/dt was calculated by dividing the change in estimated right ventricular pressure obtained using Bernoulli's principle by the time taken for the TR maximum velocity to change from one-third to two-thirds of its peak value. The outcome was divided into four categories: BV, single ventricular circulation, neonatal death and fetal death. Patients with BV were included in the BV group, while patients with single ventricular circulation, neonatal death or fetal death were included in the non-BV (NBV) group. Overall, 19 and 16 patients were included in the BV and NBV groups, respectively. The median TR maximum velocity was 3.3(range, 2.4-3.6) m/s in the BV group and 1.9(range, 1.0-3.3) m/s in the NBV group. There were no cases of postnatal BV in fetuses with TR maximum velocity < 2.4 m/s; cases with TR maximum velocity of 2.4-3.3 m/s were observed in both BV and NBV groups. Receiver-operating-characteristics-curve analysis was performed on the 11 patients in the BV group and five patients in the NBV group with a TR maximum velocity of 2.4-3.3 m/s. dP/dt ≥ 350 mmHg/s and TR maximum velocity ≥ 2.9 m/s were identified as criteria for predicting the outcome in such cases. The performance of dP/dt ≥ 350 mmHg/s in predicting BV after birth in fetuses with TVD or Ebstein's anomaly was higher compared to that of TR maximum velocity ≥ 2.9 m/s (sensitivity, 90.9% vs 72.3% and specificity, 80.0% vs 80.0%, respectively). In fetuses with TVD or Ebstein's anomaly, the postnatal outcome may be BV or NBV when the TR maximum velocity is 2.4-3.3 m/s. In such cases, by combining the TR maximum velocity with dP/dt ≥ 350 mmHg/s, BV after birth may be predicted with greater accuracy. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

The effect of hypocapnia on systemic perfusion in patients with single ventricle after surgery

The objective:the aim of the study was to identify the relationship between arterial hypocapnia and systemic hypoperfusion in newborns with single ventricular physiology after hemodynamic correction of congenital heart disease. Subjects and methods.125 newborns with congenital heart defects operated from 2014 to 2018 were examined retrospectively. Arterial and central venous blood gases were collected in the postoperative period. A total of 670 pairs of laboratory results were selected.Results.Based on the presence/absence of hypocapnia (PaCO2 less than 35 mm Hg), 2 groups were formed. Group G-0 (the hypocapnic variant of the single-ventricular circulation) comprised 44 observations. Group G-1 (PaCO2 more than 35 mm Hg) included 40 observations. In 32 (38%) cases the level of systemic perfusion was within the normal range, in 52 (62%) cases, systemic hypoperfusion was detected. In samples corresponding to Group G-1, signs of DOS were observed in 20 cases. The study showed that the most pronounced intergroup difference in parametric data was observed among indicators reflecting oxygen consumption and, as a consequence, the system flow rate (РO2 in mixed venous blood, saturation in mixed venous blood, arterio-venous difference in saturation, O2 content in venous blood, O2 extraction ratio, arterio-venous difference in РCO2). In addition, the HF markers such as arterio-venous difference in saturation, O2 extraction ratio, arterio-venous difference in РCO2 had a strong correlation with the signs of systemic hypoperfusion. In the hypocapnic group, the tendency for more pronounced desaturation of venous blood was determined, and a higher arterio-venous difference in saturation, O2 content in venous blood, O2 extraction ratio, and arterio-venous difference in РCO2 parameters were also noted.Conclusions.Arterial hypocapnia may be a sign of pulmonary overflow and reduction of systemic blood flow in newborns with single ventricular physiology, after hemodynamic correction of congenital heart disease. When managing newborns with parallel circulation, hypocapnia should be avoided as a factor contributing to the redistribution of blood flow from left to right and the development of systemic hypoperfusion.

Mathematical modeling of the Fontan blood circulation supported with pediatric ventricular assist device

The decompensated univentricular circulation is identified as one of the most challenging conditions and the application of the mechanical circulatory support (MCS) devices is proposed as therapeutic option for Fontan failure. Modelling methodologies are reported to identify the optimized types, extent and duration of required hemodynamic support using MCS. The specific parameters of device-body interaction during support of failing Fontan circulation within the design points of dedicated pediatric ventricular assist devices has not been previously defined. In this work, we introduce a mathematical model developed to simulate the interaction between the Fontan single-ventricular circulation and a constant-flow pediatric ventricular assist device (VAD) Sputnik. The interaction is studied at a pump rotor speed of 5000–9000 rpm. This simulation demonstrates that the pump replacing pulmonary ventricle of the heart creates necessary pressure differential between the systemic veins (7 mmHg) and the pulmonary artery (17.3 mmHg). Moreover, it increases the venous return that, according to the Frank-Starling mechanism, increases the stroke volume up to 32 ml/bpm (26 ml/bpm - without using a pump). For the first time, a simulation for the pediatric VAD Sputnik has been carried out. The simulation results confirm pediatric VAD Sputnik can be a possible tool to normalize the Fontan circulation in pediatric patients.

Clinical analysis of prenatal ultrasound diagnosis of fetal cardiovascular malformations in the first and second trimesters of pregnancy: A CARE-compliant article.

Fetal cardiovascular malformations is widely focused and screened, but the accuracy of screening is not satisfactory. In this study, we compared the types of congenital heart malformation, accompanying diseases and fetal outcomes in the first and second trimesters of pregnancy to clarify the advantage of early screening.From January 2013 to June 2018, 230 fetuses were diagnosed with congenital heart malformations using ultrasound method in Qilu Hospital of Shandong University, and divided into 2 groups:the first trimester fetuses (group A) and the second trimester fetuses (group B). In addition, we collected and organized medical data of 347 cases diagnosed with congenital heart disease during 1998 to 2005 (group C). We compared the spectrum of congenital heart disease, associated comorbidities and outcome of fetuses diagnosed with congenital heart disease.There were differences in the types and incidence of cardiac malformations between the first and second trimesters of pregnancy. The number of cases of non-cardiac malformation, congenital heart disease with single ventricular circulation, fetal intrauterine death and premature pregnancy termination was significantly lower in the late stage (group A and group B) than that in the early stage (group C). More patients were screened for trisomy 21, 18, 13 syndromes and Turner syndrome in group A than group B (P <.001). More fetuses with a 22q11 deletion were screened in group B than group C.Early pregnancy screening using ultrasound diagnosis is very important for fetuses with congenital heart disease.

Mid-term result of atrioventricular valve replacement in patients with a single ventricle.

Atrioventricular valve replacement is the last option to treat the atrioventricular valve regurgitation in single ventricle. This study investigates the mid-term outcomes of the atrioventricular valve replacement based on the Japan Cardiovascular Surgery Database registry. From 2008 to 2014, 56 patients [34 males (61%) and 22 females (39%)] with a single ventricular circulation, underwent atrioventricular valve replacement. Questionnaires were collected to review operative data, mid-term mortality, morbidity and redo replacement. Risk factor analysis was performed by the Cox regression model for death and redo replacement. Heterotaxy, a right systemic ventricle and a common atrioventricular valve was present in 46% (26/56), 64% and 57% of patients, respectively. The most common timings for atrioventricular valve replacement were the interstage between the second and third palliations (34%) and after the Fontan operation (34%). Twenty died during the 3.7 ± 2.6-year follow-up. Eleven received redo atrioventricular replacement. The cumulative incidences of redo atrioventricular valve replacement and survival at 3 years were 20% [95% confidence interval (CI) 9-30] and 66% (95% CI 55-80), respectively. Univariable Cox regression analysis revealed that a tricuspid valve was a risk factor for redo valve replacement [hazard ratio (HR) 6.76, 95% CI 1.79-25.6; P = 0.005] and that young age was a risk factor for death (HR 0.77, 95% CI 0.62-0.96; P = 0.019). Fourteen patients required a pacemaker implantation. Valve replacement for uncontrollable atrioventricular valve regurgitation in single ventricular circulation was associated with a moderately high risk of death, redo replacement and pacemaker implantation, whereas valve replacement at a later period and with a larger prosthetic valve size was associated with low mortality.

Anaesthetic Management of Parturients With Univentricular Congenital Heart Disease and the Fontan Operation

(Int J Obstet Anesth. 2016;28:83–91) Over the past few decades, as surgical treatment of congenital heart disease (CHD) has improved, an increasing number of women with CHD are becoming pregnant and obstetric anesthesiologists must be able to manage these women during labor and delivery. One of the newest challenges is that presented by women with a single ventricular circulation that has been palliated with the Fontan operation.

Ventricular fibrogenesis activity assessed by serum levels of procollagen type III N-terminal amino peptide during the staged Fontan procedure

ObjectiveWe tested the hypotheses that volume overload and cyanosis observed in the pre-Fontan single ventricular circulation are associated with increased ventricular fibrogenesis, that the Fontan procedure helps to reduce fibrogenesis, and that persistently increased fibrogenesis in the Fontan ventricle is associated with ventricular diastolic dysfunction. MethodsLevels of serum amino-terminal procollagen type III, a marker of tissue fibrogenesis, were measured in 172 patients with single ventricle circulation and 149 controls. Patients were divided into 3 groups according to surgical stage: 59 patients after Blalock–Taussig shunt or pulmonary banding, 60 patients after Glenn surgery (Glenn group), and 53 patients after Fontan surgery (Fontan group). ResultsSerum amino-terminal procollagen type III levels were significantly higher among the 3 single ventricle groups than among control patients, but decreased with each surgical stage (0.604, 0.176, 0.143, and 0.073 U/mL, for Blalock–Taussig shunt or pulmonary banding, Glenn, Fontan, and controls, respectively). Severity of volume load and cyanosis were independent determinants of increased amino-terminal procollagen type III levels in patients before Fontan surgery, and persistently increased amino-terminal procollagen type III after Fontan surgery was associated with ventricular diastolic stiffening (r = 0.494, P = .009). Data also indicated close associations between amino-terminal procollagen type III levels and activation of the renin–angiotensin–aldosterone system, suggesting potential involvement of this hormonal system in the increased fibrogenesis after Fontan surgery. ConclusionsThese results suggest that serum amino-terminal procollagen type III may provide important diagnostic information on myocardial fibrosis in patients with single ventricle circulation and raise the possibility that ventricular fibrogenesis may be a potential therapeutic target in this population.

Epigenetic modification in congenital heart diseases by using stem cell technologies

Congenital heart diseases are the most common birth defects, occurring in more than 1% of newborns. The gene regulatory network of cardiac development has been revealed and some cases of congenital heart diseases have been shown to be associated with cardiac-specific gene mutations or related chromosomal abnormalities; however, almost all cases of congenital heart diseases are sporadic and the pathogenesis of heart malformations still remains unknown. Recently, studies of epigenetic regulation have been making progress in the field of cardiac development and the accumulated knowledge helps us understand more about cardiogenesis and congenital heart diseases. Interestingly, pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have attracted attention as tools to dissect epigenetic regulation during differentiation. Reprogramming and differentiation of ES cells and iPS cells can be induced by changes of gene expression patterns and epigenetic regulation, not by changing DNA sequences. We can also modify histone patterns and chromatin structures using chemical reagents. Hence, pluripotent stem cells enable us to dissect and modify epigenetic regulation during cardiogenesis in vitro. Moreover, in terms of iPS cells, they have become disease models because they can be generated from the somatic cells of patients. In this review, we summarize the recent findings of epigenetic regulation in cardiac development and congenital heart diseases. We also review the epigenetic modification during the reprogramming and cardiac differentiation of ES cells and iPS cells, and introduce our study showing that the disease-specific iPS cells of hypoplastic left heart syndrome, one of the severest congenital heart diseases with single ventricular circulation, exhibit unique epigenetic regulation during differentiation. Furthermore, we briefly focus on modifications of epigenetic regulation in cardiac development using chemical reagents, which suggest the possibility of treating congenital heart diseases using drugs. Lastly, we discuss the epigenetic memory of iPS cells, a specific feature that often complicates or prevents study of the differentiation of iPS cells.

Right Ventricular Failure and Pathobiology in Patients with Congenital Heart Disease – Implications for Long-Term Follow-Up

Right ventricular dysfunction represents a common problem in patients with congenital heart defects, such as Tetralogy of Fallot or pulmonary arterial hypertension. Patients with congenital heart defects may present with a pressure or volume overloaded right ventricle (RV) in a bi-ventricular heart or in a single ventricular circulation in which the RV serves as systemic ventricle. Both subsets of patients are at risk of developing right ventricular failure. Obtaining functional and morphological imaging data of the right heart is technically more difficult than imaging of the left ventricle. In contrast to findings on mechanisms of left ventricular dysfunction, very little is known about the pathophysiologic alterations of the right heart. The two main causes of right ventricular dysfunction are pressure and/or volume overload of the RV. Until now, there are no appropriate models available analyzing the effects of pressure and/or volume overload on the RV. This review intends to summarize clinical aspects mainly focusing on the current research in this field. In future, there will be increasing attention to individual care of patients with right heart diseases. Hence, further investigations are essential for understanding the right ventricular pathobiology.

Abstract 16998: Ventricular Systolic and Diastolic Dyssynchrony and Their Relationship with Ventricular Function in Patients with Single Ventricular Circulation

BACKGROUND: Recent studies highlighted importance of ventricular diastolic dyssynchrony as well as systolic dyssynchrony in the pathophysiology of adult heart failure. However, little is known about interaction between diastolic and systolic dyssynchrony and their impacts on ventricular function in pediatric patients with single ventricular circulation. METHODS: We studied 24 pediatric patients (mean age; 2.1±1.3 years) with single ventricular circulation and 12 age-matched control subjects. Transthoracic two-demensional speckle tracking echocardiography (Vivid 7, GE) was performed to assess ventricular dyssynchrony (EchoPac workstation, GE). Systolic and diastolic dyssynchrony was measured as a maximal time delay in peak systolic and early diastolic velocities of longitudinal strain at four segments. Comprehensive ventricular systolic and diastolic function was assessed by employing pressure-area relationships during preload varied by transient inferior vena caval balloon obstruction. RESULTS: Systolic and diastolic time delay were 31.8±14.5 ms and 29.2±14.6 ms respectively in single ventricular patients, and were significantly larger than in the controls (16.2±11.9 ms for systolic and 15.8±11.2 ms for diastolic, both p&lt;0.01). There was no significant correlation between systolic and diastolic dyssynchrony in the patient group. Systolic dyssynchrony was negatively correlated with ventricular contractility indexes of end-systolic elastance (r=0.34, p&lt;0.05) and maximum rate of pressure rise (r=0.585, p&lt;0.05). Diastolic dyssynchrony was positively correlated with end-diastolic pressure (r=0.719, p&lt;0.05), but not with time constant of ventricular relaxation. CONCLUSIONS: Not only systolic but also diastolic dyssynchrony has important impacts on ventricular function in patients with single ventricular circulation. These data suggest important notion that diastolic as well as systolic dyssynchrony is an important therapeutic target when considering cardiac resynchronization therapy for patients with single ventricular circulation.

Precise evaluation of bilateral pulmonary artery banding for initial palliation in high-risk hypoplastic left heart syndrome

In patients with high-risk hypoplastic left heart syndrome (HLHS), the Norwood operation (NW) in the neonatal period still results in high mortality compared with other cardiac surgery. Bilateral pulmonary artery banding (bPAB), a very effective initial procedure for HLHS, for which the specific evaluation is as yet unsatisfactory, was performed, and we report our findings in the present study. We have performed bPAB since 2006. A total of 17 patients with HLHS or a variant underwent bPAB before the NW. Echocardiography was performed between bPAB and the NW, and the flow acceleration just after bPAB and before NW was evaluated. Before the NW, a catheter examination was also performed. bPAB was performed at 6.6 ± 0.6 days of age, and the NW at 130 ± 88 days. The patients' mean body weight (BW) was 2.5 ± 0.4 kg at bPAB and 4.0 ± 1.1 kg at the NW. The length of the tape for bPAB was 9.9 ± 0.6 mm in the right pulmonary artery (RPA) and 9.4 ± 0.6 mm in the left (LPA) because the RPA was usually wider than the LPA. The tape width was 2 mm in all cases. The catheter examination was performed at 95 ± 85 days after bPAB. The arterial oxygen saturation (SaO₂) was 71% ± 8.6%. Multivariate regression analysis revealed that SaO₂ was estimated well using 4 factors: the banding size of the RPA, BW at bPAB, BW at NW, and BW in the period between bPAB and catheter examination (R² = 0.79). Echocardiography just after bPAB showed that the blood flow at the bPAB had accelerated to 3.0 ± 0.8 m/s in the RPA and 3.3 ± 0.8 m/s in the LPA (P = .004). The estimated pressure gradient was 39.2 ± 17.6 mm Hg in the RPA and 46.1 ± 23.0 mm Hg in the LPA (P = .006). The blood flow at bPAB was accelerated to 3.7 ± 0.7 m/s in the RPA and 4.0 ± 0.6 m/s in the LPA before NW (P = .013). The estimated pressure gradient was 62.6 ± 27.6 mm Hg in the RPA and 56.1 ± 19.6 mm Hg in the LPA before NW (P = .014). The catheter examination revealed mean wedge pressures of 18.0 ± 7.2 mm Hg for the RPA and 16.2 ± 4.3 mm Hg for the LPA. The operative mortality rate was 0%. One patient required a repeat operation to adjust the bPAB, and prolonged pleural effusion was observed in 1 case. The postoperative SaO₂ after bPAB correlated closely with the banding size and BW at bPAB, NW and during the period after bPAB. Because the mean PA pressure before NW was low enough for single ventricular circulation, the bPAB in this study was an effective option for high-risk patients undergoing HLHS or a variant. We believe the bPAB sizes used were suitable and were determined as follows: BW plus 7 mm for the LPA and BW plus 7.5 mm for the RPA.

Impaired Pulmonary Perfusion Associated With Thymus Hyperplasia in an Infant Candidate for Fontan Operation

An enlarged thymus adversely affected pulmonary artery development and perfusion in a 4-month-old boy with asplenia syndrome and a single ventricular circulation with aorto-pulmonary shunt. Steroid administration for 4 weeks successfully reduced thymus volume, concomitant with improvement of pulmonary vasculature and perfusion. Given the importance of pulmonary physiology in the Fontan circulation, the effects of thymic hyperplasia on pulmonary circulation should be taken into consideration in the overall management of candidates for Fontan surgery.