Pulsatile venous waveform quality affects the conduit performance in functional and "failing" Fontan circulations.

OBJECTIVE: To investigate the effect of pulsatility of venous flow waveform in the inferior and superior caval vessels on the performance of functional and "failing" Fontan patients based on two primary performance measures - the conduit power loss and the distribution of inferior caval flow (hepatic factors) to the lungs. METHODS: Doppler angiography flows were acquired from two typical extra-cardiac conduit "failing" Fontan patients, aged 13 and 25 years, with ventricle dysfunction. Using computational fluid dynamics, haemodynamic efficiencies of "failing", functional, and in vitro-generated mechanically assisted venous flow waveforms were evaluated inside an idealised total cavopulmonary connection with a caval offset. To investigate the effect of venous pulsatility alone, cardiac output was normalised to 3 litres per minute in all cases. To quantify the pulsatile behaviour of venous flows, two new performance indices were suggested. RESULTS: Variations in the pulsatile content of venous waveforms altered the conduit efficiency notably. High-frequency and low-amplitude oscillations lowered the pulsatile component of the power losses in "failing" Fontan flow waveforms. Owing to the offset geometry, hepatic flow distribution depended strongly on the ratio of time-dependent caval flows and the pulsatility content rather than mixing at the junction. "Failing" Fontan flow waveforms exhibited less balanced hepatic flow distribution to lungs. CONCLUSIONS: The haemodynamic efficiency of single-ventricle circulation depends strongly on the pulsatility of venous flow waveforms. The proposed performance indices can be calculated easily in the clinical setting in efforts to better quantify the energy efficiency of Fontan venous waveforms in pulsatile settings.

Adult definitions for dyssynchrony are inappropriate for pediatric patients.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a promising approach to improve cardiac function in children in heart failure with cardiomyopathy. Cardiac timing measures in pediatrics are typically based on age and heart rate. However, pediatric CRT studies to date have used adult based timing cutoff values. We investigated the applicability of using these adult standards in pediatric patients with normal hearts. METHODS: We studied 88 outpatients referred for cardiac evaluation who had a normal cardiac evaluation. Subjects had 12 lead EKG and normal echocardiogram. Patients with known heart disease or abnormal rhythms were excluded. 2D echo and Doppler including color tissue Doppler imaging (TDI, Vivid 7 GE Ultrasound, Norway) were obtained. TDI was performed on three standard apical views (four chamber, two chamber, and long axis). Longitudinal dyssynchrony was determined from (1) Yu index--standard deviation of differences in timing of peak TDI velocity of all 12 basal and mid LV wall segments, adult cutoff >32 ms and (2) opposing wall difference (OWD) in timing of peak TDI velocity of 12 LV wall segments, adult cutoff >65 ms. Radial dyssynchrony was determined from differences in timing of peak radial strain between anterior-septal and posterior LV segments from speckle tracking of 2D LV views, adult cutoff >130 ms. RESULTS: Median age was 11.5 years; median heart rate was 74.5. Longitudinal dyssynchrony was present in 40% of normals based on Yu index, and in 43% based on OWD. No child had Radial dyssynchrony. CONCLUSIONS: This pilot study of children with normal hearts suggests that current adult CRT dyssynchrony cutoff values are inappropriate in the pediatric population.

Optimization of inflow waveform phase-difference for minimized total cavopulmonary power loss.

The Fontan operation is a palliative surgical procedure performed on children, born with congenital heart defects that have yielded only a single functioning ventricle. The total cavo-pulmonary connection (TCPC) is a common variant of the Fontan procedure, where the superior vena cava (SVC) and inferior vena cava (IVC) are routed directly into the pulmonary arteries (PA). Due to the limited pumping energy available, optimized hemodynamics, in turn, minimized power loss, inside the TCPC pathway is required for the best optimal surgical outcomes. To complement ongoing efforts to optimize the anatomical geometric design of the surgical Fontan templates, here, we focused on the characterization of power loss changes due to the temporal variations in between SVC and IVC flow waveforms. An experimentally validated pulsatile computational fluid dynamics solver is used to quantify the effect of phase-shift between SVC and IVC inflow waveforms and amplitudes on internal energy dissipation. The unsteady hemodynamics of two standard idealized TCPC geometries are presented, incorporating patient-specific real-time PC-MRI flow waveforms of "functional" Fontan patients. The effects of respiration and pulsatility on the internal energy dissipation of the TCPC pathway are analyzed. Optimization of phase-shift between caval flows is shown to lead to lower energy dissipation up to 30% in these idealized models. For physiological patient-specific caval waveforms, the power loss is reduced significantly (up to 11%) by the optimization of all three major harmonics at the same mean pathway flow (3 L/min). Thus, the hemodynamic efficiency of single ventricle circuits is influenced strongly by the caval flow waveform quality, which is regulated through respiratory dependent physiological pathways. The proposed patient-specific waveform optimization protocol may potentially inspire new therapeutic applications to aid postoperative hemodynamics and improve the well being of the Fontan patients.

Regional myocardial velocities and isovolumic contraction acceleration before and after device closure of atrial septal defects: a color tissue Doppler study.

BACKGROUND: The study analyzed the effect of atrial septal defect (ASD) device closure on regional wall motion in the right (RV) and left ventricles (LV) using color tissue Doppler imaging (TDI). Atrial septal defect closure results in acute volume unloading of the RV. For unknown reasons, some patients develop acute left-sided heart failure postintervention. METHODS: Color TDI was performed in 39 pediatric ASD and 75 age-matched controls. Regional wall motion in 5 LV and 1 RV segment were analyzed before, immediately after, and 24 hours after interventional ASD closure. Off-line postprocessing of echocardiographic data was used to determine myocardial velocities and acceleration during isovolumic contraction (IVA). Isovolumic contraction acceleration is the slope of the upstroke of the isovolumic contraction wave (IVA = peak velocity/acceleration time). RESULTS: At baseline, patients with ASD had significantly higher RV systolic velocities than controls. Isovolumic contraction acceleration was similar in patients with ASD and controls. In the catheterization laboratory postintervention, conventional function parameters remained stable but systolic myocardial velocities decreased significantly in all segments. Diastolic velocities fell in LV segments but not in the RV. In contrast to velocities, IVA was stable during ASD device closure. On follow-up at 24 hours, myocardial velocities had normalized. CONCLUSIONS: Device closure of ASD results to an acute transient decrease of regional myocardial velocities in the LV and RV, whereas the load-insensitive marker isovolumic acceleration remained stable. Therefore, the velocity changes may represent a response to altered left and right ventricular loading conditions. Color TDI is a sensitive tool to analyze ventricular mechanics.

Non-invasive detection of acute allograft rejection in children by tissue Doppler imaging: myocardial velocities and myocardial acceleration during isovolumic contraction.

BACKGROUND: In adults, an acute decrease of regional myocardial velocities is a sensitive marker of rejection. In children, velocities are more variable. A new marker, myocardial acceleration during isovolumic contraction (IVA), appears to be less age-dependent than myocardial velocities. This study therefore compared tissue Doppler (TDI)-derived velocities and IVA as potential rejection markers for children. METHODS: TDI was performed in 15 pediatric heart transplant recipients (age 8.0 +/- 3.6 years) during acute rejection and at baseline without rejection, 50 additional transplant children without rejection (7.8 +/- 5.9 years) and 30 age-matched healthy children (7.5 +/- 5.2 years). Color Doppler cine-loops of 3 cardiac cycles were stored as echocardiographic raw data. Using off-line post-processing, systolic (S) and diastolic (E) myocardial velocities and IVA were measured in 5 basal left ventricular segments. IVA is the peak isovolumic contraction wave velocity divided by acceleration time. RESULTS: Without rejection, transplant children had significantly lower diastolic velocities (basal lateral E 10.4 +/- 2.9 vs 11.9 +/- 2.6 cm/s; p < 0.001) and systolic velocities (S 5.6 +/- 1.4 vs 7.1 +/- 2.0 cm/s; p < 0.001) than normal age-matched controls, but IVA was similar (1.2 +/- 1.4 vs 1.3 +/- 0.5 m/s2). During rejection, all markers decreased significantly compared with age-matched normal control, the non-rejecting transplant group and individual baseline values. CONCLUSIONS: Regional myocardial velocities change significantly during acute allograft rejection in children. However, many children already have wall motion abnormalities at baseline, so results are often difficult to interpret. In contrast, isovolumic acceleration was normal without rejection and selectively decreased during the event. IVA is a promising non-invasive rejection marker for pediatric patients.

Design and baseline characteristics of participants in the study of antihypertensive therapy in children and adolescents with autosomal dominant polycystic kidney disease (ADPKD).

In this manuscript, we describe our ongoing randomized clinical trial to assess the efficacy of blood pressure control with angiotensin converting enzyme (ACE) inhibition on renal cyst growth over a 5-year study period in children and young adults aged 4-21 years with autosomal dominant polycystic kidney disease (ADPKD). Baseline demographic and laboratory data for the study groups are reported. Results of this study could significantly impact the standard of care for management of ADPKD in this population.

Insights into the effect of aortic compliance on Doppler diastolic flow patterns seen in coarctation of the aorta: a numeric study.

BACKGROUND: In the echocardiographic evaluation of coarctation of the aorta, the degree of antegrade diastolic flow (diastolic runoff) noted on spectral Doppler tracings traditionally was thought to be solely dependent on lesion severity. However, recent in vitro experiments suggest the presence of this spectral Doppler pattern is as much related to the severity of coarctation as it is with changes in aortic compliance. Using state-of-the-art, multidisciplinary, numeric analysis tools, the purpose of this study was to investigate the specific fluid and wall mechanics present in coarctation of the aorta to further understand these relationships. METHODS: Three computational numeric models of coarctation were developed with high, low, and no wall compliance. Flow simulations were run representing high- and low-flow states. RESULTS: In both the low- and high-flow states, the degree of diastolic runoff increased with increasing vessel compliance. The high compliance model had larger changes in aortic dilatation in the precoarctation region compared with the low compliance model. CONCLUSIONS: Increased aortic compliance brings about greater dilatation of the precoarctation aorta in systole, resulting in a persistence of stored upstream energy. This stored energy, released downstream in diastole as the precoarctation aortic walls contract, leads to increased degrees of diastolic runoff. Numeric methods offer a unique perspective into the mechanisms behind such clinical measures.

Minimal sedation second dose strategy with intranasal midazolam in an outpatient pediatric echocardiographic setting.

BACKGROUND: Anxiety and movement in children during transthoracic echocardiography (TTE) can compromise study quality and reliability. Minimal sedation is often required. Intranasal midazolam (INM), used in various procedures, is an excellent sedative. Optimal INM dosing strategies for uncooperative children undergoing TTE are largely unknown, including second-dose INM strategies, introduced to maximize the potential for successful sedation and minimize risk. The purpose of this retrospective review was to evaluate the effectiveness of a second-dose INM minimal sedation strategy recently adopted at the Children's Hospital of Pittsburgh. METHODS: The strategy incorporates a second dose of INM if needed (10-15 minutes after the first dose) to obtain the desired level of anxiolysis. The effectiveness of this strategy was assessed in 100 consecutive patients (age range, 1-59 months). RESULTS: There were no reported complications, minimal untoward side reactions, and no delays in discharge. Eighty patients attained satisfactory minimal sedation levels. CONCLUSION: A second-dose INM strategy was effective in achieving satisfactory minimal sedation in children undergoing TTE. The results of this study also suggest that only a small proportion of patients would benefit from a one-dose INM strategy.

Altered ventricular mechanics in cardiac allografts: a tissue Doppler study in 30 children without prior rejection events.

BACKGROUND: Tissue Doppler imaging (TDI), a non-invasive echocardiography technique, permits quantitative analysis of the regional distribution pattern of myocardial velocities. During normal childhood development, regional function changes markedly, including an increasing predominance of longitudinal velocities. This study analyzed the impact of heart transplantation on ventricular mechanics in growing children. METHODS: TDI was performed in 30 pediatric heart transplant recipients (7.1 +/- 6.2 years) and 32 age-matched healthy children (6.8 +/- 5.4 years). Patients had no rejection history and were 3.1 years (median) post-transplant. Color TDI images from apical and parasternal views were stored as echocardiographic raw data. Off-line analysis was used to measure peak systolic and diastolic myocardial velocities in 6 basal cardiac segments for longitudinal (anterior, inferior, lateral, septal, right ventricle) and radial velocities (posterior). Isovolumic acceleration, a load-insensitive function marker, was determined as slope of the upstroke of the isovolumic contraction wave. Multiple regression modeling was used for statistics. RESULTS: Systolic myocardial velocities still increased with age after transplantation, but the velocity distribution pattern was changed. In transplanted hearts, left ventricular longitudinal velocities were lower and radial velocities were higher than in the controls, but isovolumic acceleration was similar. In the right ventricle, longitudinal velocities and isovolumic acceleration were significantly decreased after transplantation. Wall motion abnormalities were present in 50% of patients. CONCLUSIONS: Regional wall motion analysis shows significant alterations of the fundamental biomechanical pump function of the left ventricle after heart transplantation in children, with a shift from longitudinal to radial fibers and depressed right ventricular wall motion. This may have important implications for the long-term graft function required in children.

Designing the optimal Total Cavopulmonary Connection: pulsatile versus steady flow experiments.

BACKGROUND: The Total Cavopulmonary Connection (TCPC), used for repair of patients with single ventricle physiology, creates a passive system of blood flow into the pulmonary circulation where enhanced energy efficiency may lead to improved long term patient outcomes. Previous numerical and in vitro studies using steady flow have shown that incorporation of SVC (superior vena cava) and IVC (inferior vena cava) offsets lead to decreased energy losses. We hypothesize that the optimal TCPC offset design found in these previous steady flow experiments may not be the optimal design in pulsatile flow situations. MATERIAL/METHODS: 3-D finite volume numerical models were used to simulate flow through the total cavopulmonary connection. We ran steady and pulsatile flow experiments through 4 TCPC designs each with different SVC to IVC offsets (0.1/4, 1/2, 1 diameter offsets). The total energy (power) loss for each TCPC model was calculated. RESULTS: In steady flow experiments, % difference in energy loss between the most optimal and least optimal design was 26%. In contrast, in pulsatile flow experiments the % difference was only 8%. CONCLUSIONS: Our results demonstrate the improvements in energy loss seen using SVC-IVC offsets in steady flow experiments do not necessarily translate to pulsatile flow situations. Overall there was lower differences in efficiency between all TCPC designs in the pulsatile flow experiments. These results emphasize the need for further studies to fully define the relationship between energy losses and TCPC vessel architecture in non-steady flow physiologic situations.

Influence of connection geometry and SVC-IVC flow rate ratio on flow structures within the total cavopulmonary connection: a numerical study.

The total cavopulmonary connection (TCPC) is a palliative cardiothoracic surgical procedure used in patients with one functioning ventricle that excludes the heart from the systemic venous to pulmonary artery pathway. Blood in the superior and inferior vena cavae (SVC, IVC) is diverted directly to the pulmonary arteries. Since only one ventricle is left in the circulation, minimizing pressure drop by optimizing connection geometry becomes crucial. Although there have been numerical and in-vitro studies documenting the effect of connection geometry on overall pressure drop, there is little published data examining the effect of SVC-IVC flow rate ratio on detailed fluid mechanical structures within the various connection geometries. We present here results from a numerical study of the TCPC connection, configured with various connections and SVC:IVC flow ratios. The role of major flow parameters: shear stress, secondary flow, recirculation regions, flow stagnation regions, and flow separation, was examined. Results show a complex interplay among connection geometry, flow rate ratio and the types and effects of the various flow parameters described above. Significant changes in flow structures affected local distribution of pressure, which in turn changed overall pressure drop. Likewise, changes in local flow structure also produced changes in maximum shear stress values; this may have consequences for platelet activation and thrombus formation in the clinical situation. This study sheds light on the local flow structures created by the various connections andflow configurations and as such, provides an additional step toward understanding the detailed fluid mechanical behavior of the more complex physiological configurations seen clinically.

First-order system least squares for elastohydrodynamics with application to flow in compliant blood vessels.

Mathematical modeling of compliant blood vessels generally involves the Navier-Stokes equations on the evolving fluid domain and constitutive structural equations on the tissue domain. Coupling these systems while accounting for the changing shape of the fluid domain is a major challenge in numerical simulation. Many techniques have been developed to model compliant vessels, but all suffer from disproportionate increase in computational cost as problem complexity increases (i.e., larger domains, more dimensions, and more variables.). Even the best standard methods result in computational cost that typically grows quadratically with the degrees of freedom. Using a least-squares formulation of the problem, elliptic grid generation for the changing fluid domain, and an algebraic multigrid solver for the linear system can overcome many shortcomings of standard techniques. Most notably, the computational cost of solving the problem increases linearly with the degrees of freedom and the associated functional provides an a posteriori error measurement. Least squares represents a systematic approach for formulating the original problem so that the numerical process becomes straightforward and optimal, and it avoids restrictions that often limit other methods. Results are presented for a two-dimensional test problem consisting of a Newtonian fluid with properties of blood in a linear-elastic vessel with properties of smooth muscle.