The cardiac torsion as a sensitive index of heart pathology: A model study.

The torsional behaviour of the heart (i.e. the mutual rotation of the cardiac base and apex) was proved to be sensitive to alterations of some cardiovascular parameters, i.e. preload, afterload and contractility. Moreover, pathologies which affect the fibers architecture and cardiac geometry were proved to alter the cardiac torsion pattern. For these reasons, cardiac torsion represents a sensitive index of ventricular performance. The aim of this work is to provide further insight into physiological and pathological alterations of the cardiac torsion by means of computational analyses, combining a structural model of the two ventricles with simple lumped parameter models of both the systemic and the pulmonary circulations. Starting from diagnostic images, a 3D anatomy based geometry of the two ventricles was reconstructed. The myocytes orientation in the ventricles was assigned according to literature data and the myocardium was modelled as an anisotropic hyperelastic material. Both the active and the passive phases of the cardiac cycle were modelled, and different clinical conditions were simulated. The results in terms of alterations of the cardiac torsion in the presence of pathologies are in agreement with experimental literature data. The use of a computational approach allowed the investigation of the stresses and strains in the ventricular wall as well as of the global hemodynamic parameters in the presence of the considered pathologies. Furthermore, the model outcomes highlight how for specific pathological conditions, an altered torsional pattern of the ventricles can be present, encouraging the use of the ventricular torsion in the clinical practice.

A new method to evaluate patient characteristic response to ultrafiltration during hemodialysis.

BACKGROUND: Several factors are involved in the pathogenesis of dialysis discomfort interfering with optimal fluid removal and reducing the efficacy of the treatment; the most important one is a decrease in blood volume caused by an imbalance between ultrafiltration (UF) and plasmarefilling (PR) rates. OBJECTIVES: This study is aimed at devising a method to tailor the dialysis therapy to each individual patient, by analyzing the relationship between PR and UF during the sessions in stable patients and widening the knowledge of fluid exchanges during the treatment. METHODS: Thirty stable patients undergoing maintenance hemodialysis were enrolled. Three dialysis sessions were monitored for each patient; systemic pressure, blood composition, blood volume % variation, weight loss and conductivity were recorded repeatedly. A Plasma Refilling Index (PRI), defined and calculated by means of parameters measured throughout the dialysis, was introduced as a novel instrument to study plasma refilling phenomena. Results. The PRI provides understanding of patient response (in terms of plasma refilling) to the set UF. In the monitored sessions, the PRI trend is found to be characteristic of each patient; a PRI course that is at variance with the characteristic trend is a signal of inadequate or unusual dialysis scheduling. Moreover, statistical analysis highlights two different PRI trends during the first hour and during the rest of the treatment, suggesting the presence of different treatment phases. CONCLUSION: The main advantage of the PRI index is that it is non-invasive peculiar to each patient and easy to compute in a dialysis routine based on online data recorded by the monitor. A deviation from the characteristic trend may be a warning for the clinician. The analysis of the PRI trend also suggests how to modulate UF as a function of interstitial to intravascular fluid removal balance during dialysis.

Clinical evaluation of internal hemodiafiltration (iHDF): a diffusive-convective technique performed with internal filtration enhanced high-flux dialyzers.

AIM: Efficiency in removing middle molecules such as beta2-microglobulin (beta2-MG) is one of the main purposes of modern dialytic therapy. In order to achieve this, techniques requiring complex machines and substitution fluid have been developed over recent years. Alternatively, the internal filtration/back filtration phenomenon can be used. The recent development of a so-called "internal filtration enhanced dialyser" prompted us to compare the removal of beta2-MG together with other small molecules when the dialyser was used either in standard hemodiafiltration (HDF) or internal hemodiafiltration (iHDF). METHODS: Ten stable, anuric, hemodialysis (HD) patients treated by thrice weekly standard bicarbonate HD using low-flux synthetic membrane entered the study. A new high-flux polysulfone dialyser designed with the specific aim of enhancing internal filtration (BS-1.6 UL, 1.6 m2, Toray Industries) was used. Post dilution HDF (2.5 l/hour of substitution fluid, dialysate flow 500 ml/min) was compared with iHDF (dialysate flow 750 ml/min), with blood flow at 300 ml/min. Samples were obtained at the start and at the end of the session in order to measure the % removal of urea, creatinine, uric acid, phosphate and beta2-MG (corrected for total protein concentration). In addition, after 20 min of dialysis the clearances of the same molecules were measured. A mathematical model has been developed for the description of the hydrodynamic phenomena taking place within the dialyser and of fluid filtration across the membrane. RESULTS: No significant differences have been observed in removal rate switching from HDF to iHDF except for beta2-MG removal, which was slightly higher in HDF than in iHDF Phosphate clearance is significantly higher than those obtained with creatinine in both HDF (p<0.005) and iHDF (p<0.01) modalities. The total convection calculated with the model is reduced with respect to HDF only by 24% (4100 ml/h vs. 5400 ml/h on the average). CONCLUSIONS: iHDF is a high flux dialysis method, which, if performed with a dialyser designed to enhance internal filtration, obtains a much higher removal rate in comparison with dialysers in traditional high flux dialysis, as previously reported in the literature. Provided that the dialyser is used on a dialysis machine working with ultra pure dialysate and UF control, this dialyser line can perform reliable internal HDF without the need for replacement solution. Considering the narrow difference in performance observed between iHDF and HDF, and the increasing number (and age) of patients leading to higher dialysis costs, iHDF represents a cost-effective alternative to other diffusive-convective techniques.

[Prognosis of cognition in congenital hypothyroidism following early treatment. Double effect hypothesis]. / Pronostico de la cognicion en el hipotiroidismo congenito tratado precozmente. Hipotesis del doble efecto.

INTRODUCTION: The prevention of mental retardation due to congenital hypothyroidism by treating it at an early stage is one of the great achievements of contemporary preventive medicine. Nevertheless, the children suffering from this disease are affected by selective cognitive deficits whose origin remains a controversial issue. PATIENTS AND METHODS: We describe the results from a cohort of 100 children who have been diagnosed as suffering from congenital hypothyroidism in La Havana since 1989 and whose cognitive performance has since been periodically evaluated. The mean age at each evaluation was as follows: 1.1 years (mean and typical deviation: 0.3) and 8.2 years (mean and typical deviation: 1.2). RESULTS: During the first two years of life the developmental quotients are within the normal range of values, although fine oculomotor coordination is significantly diminished. The duration of fetal hypothyroidism is linked to postural control, and the initial biochemical severity of the disease is associated to language development. Oculomotor coordination is not linked to any variable concerning the severity of the disease or with the effectiveness of therapy. At school age, intelligence quotients (IQ) are also within the normal range of values. A multiple regression analysis indicated that the total IQ can be predicted from the scores in oculomotor coordination during the first two years of life and from the initial doses of levothyroxine. CONCLUSIONS: The relations between the variables capable of forecasting intellectual development in these children are analysed and we also discuss the hypothesis which suggests that some of the persisting neurocognitive deficits are probably due to genetic influences that exist regardless of the effectiveness of the therapy.

Hydraulic functional characterisation of aortic mechanical heart valve prostheses through lumped-parameter modelling.

Lumped-parameter modelling techniques are proposed as a method for studying the hydraulic characteristics of mechanical prosthetic heart valves (PHVs). The global hydraulic behaviour of PHVs in the open position was modelled by taking into account the (nonlinear) resistive and (linear) inertial factors governing the time-dependent relationship between transvalvular pressure drop and fluid flow rate, and neglecting the leaflets' opening and closure transient phenomena. Statistically defined indices associated to the parameters' values attest how properly the model describes PHV hydraulic behaviour. Local fluid dynamics is not modelled with this approach. The proposed method was implemented in a software program and applied to the characterisation of the aortic StJude Medical, StJude Medical Hemodynamic Plus and CarboMedics PHVs, basing on steady- and pulsatile-flow hydraulic-bench experimental data. The results showed that reliable parameters expressing hydraulic resistance can be derived from steady-flow data (R(2)>0.995). Inertance parameters derived from pulsatile-flow experiments are liable to a degree of uncertainty (confidence intervals up to 17%), however, comparing the reconstructed vs. measured pressure drop during systolic time demonstrates that this deficiency is mostly due to the missing description of initial, transient oscillations presumably related to the leaflets' opening (not modelled).

An approach to computer automation of the extracorporeal circulation.

In order to move towards extracorporeal circulation (ECC) automation, a virtual simulation of the process was designed. The ECC model is composed of a virtual patient linked to a virtual ECC circuit. A user interface panel allows to set control parameters for the simulation and to visualize results. It is possible to switch between manual and automatic control. Meaningful hemodynamic and hematochemical variables are continuously shown along with a score (from 0 to 10). The virtual model can play a crucial role in educating and training the personnel devoted to the managing of the heart-lung machine.

In vitro steady-flow analysis of systemic-to-pulmonary shunt haemodynamics.

A modified Blalock-Taussig shunt is a connection created between the systemic and pulmonary arterial circulations to improve pulmonary perfusion in children with congenital heart diseases. Survival of these patients is critically dependent on blood flow distribution between the pulmonary and systemic circulations which in turn depends upon the flow resistance of the shunt. Previously, we investigated the pressure-flow relationship in rigid shunts with a computational approach. to estimate the pulmonary blood flow rate on the basis of the in vivo measured pressure drop. The present study aims at evaluating, in vitro how the anastomotic distensibility and restrictions due to suture presence affect the shunt pressure-flow relationship. Two actual Gore-Tex shunts (3 and 4 mm diameters) were sutured to compliant conduits by a surgeon and tested at different steady flow rates (0.25-11 min(-1)) and pulmonary pressures (3-34 mmHg). Corresponding computational models were also created to investigate the role of the anastomotic restrictions due to sutures. In vitro experiments showed that pulmonary artery pressure affects the pressure-flow relationship of the anastomoses. particularly at the distal site. However, this occurrence scarcely influences the total shunt pressure drop. Comparisons between in vitro and computational models without anastomotic restrictions show that the latter underestimates the in vitro pressure drops at any flow rate. The addition of the anastomotic restrictions (31 and 47% of the original area of 3 and 4 mm shunts, respectively) to the computational models reduces the gap, especially at high shunt flow rate and high pulmonary pressure.

Modeling of the Norwood circulation: effects of shunt size, vascular resistances, and heart rate.

Hypoplastic left heart syndrome is the most common lethal cardiac malformation of the newborn. Its treatment, apart from heart transplantation, is the Norwood operation. The initial procedure for this staged repair consists of reconstructing a circulation where a single outlet from the heart provides systemic perfusion and an interpositioning shunt contributes blood flow to the lungs. To better understand this unique physiology, a computational model of the Norwood circulation was constructed on the basis of compartmental analysis. Influences of shunt diameter, systemic and pulmonary vascular resistance, and heart rate on the cardiovascular dynamics and oxygenation were studied. Simulations showed that 1) larger shunts diverted an increased proportion of cardiac output to the lungs, away from systemic perfusion, resulting in poorer O2 delivery, 2) systemic vascular resistance exerted more effect on hemodynamics than pulmonary vascular resistance, 3) systemic arterial oxygenation was minimally influenced by heart rate changes, 4) there was a better correlation between venous O2 saturation and O2 delivery than between arterial O2 saturation and O2 delivery, and 5) a pulmonary-to-systemic blood flow ratio of 1 resulted in optimal O2 delivery in all physiological states and shunt sizes.

A computational study of the hemodynamics after "edge-to-edge" mitral valve repair.

Edge-to-edge mitral valve repair consists in suturing the free edge of the leaflets to re-establish coaptation in prolapsing valves. The leaflets are frequently sutured at the middle and a double orifice valve is created. In order to study the hemodynamic implications, a parametric model of the left heart has been developed. Different valve areas and shapes have been investigated. Results show that the simplified Bernoulli formula provides a good estimation of the pressure drop and that the pressure drop may be predicted on the basis of the pre-operative geometric and hemodynamics data by means of customized models.

The pumping oxygenator: design criteria and first in vitro results.

A new project is presented, the pumping oxygenator, functionally integrating pulsatile pumping and blood oxygenation in a single device. Solid, semipermeable silicone membranes allow gas exchange and simultaneously transfer energy from pressurized gas to blood thanks to their distensibility and to inlet and outlet 1-way valves. Two small-sized (1 m2 exchange surface area) prototypes were designed, constructed, hydraulically characterized, and subjected to gas transfer evaluation tests. Blood flow rates (Q(b)) up to 1,250 ml/min were obtained with 30 mm Hg static preload and 130 mm Hg afterload with 0.7 m upstream and 2.1 m downstream 3/8 inch pipes. Physiological oxygen transfer (VO2 = 5 ml/dl, ml of transferred O2/dl of treated blood) was delivered at Q(b) < 900 ml/min, about 4 ml/dl at Q(b) = 1,250 ml/min. VO2 also was significantly increased by increasing percent systolic time. CO2 transfer decreased regularly with increasing Q(b) from VCO2 = 4.8 ml/dl at Q(b) = 400 ml/min to VCO 2 = 2.1 ml/dl at Q(b) = 1,250 ml/min. The results confirm the possibility of integrating oxygenation and pulsatile pumping. The pumping oxygenator represents a promising project deserving further improvements.

Humidity measurements in passive heat and moisture exchangers applications: a critical issue.

A reliable, quantitative assessment of humidification performances of passive heat and moisture exchangers in mechanically-ventilated patients is still to be achieved, although relevant efforts have been made to date. One of the major problems to tackle consists in the difficulty of humidity measurements, both in vivo (during either anaesthesia or intensive care unit treatments) and in vitro set-ups. In this paper a review of the basic operation principles of humidity sensors as well as an analysis of their usage within in vivo and in vitro tests are presented. Particular attention is devoted to the limitations arising from the specific measurement set-up, as they may affect the results notably.

Scaling approach to study the changes through the gestation of human fetal cardiac and circulatory behaviors.

During human gestation, fetal body size increases considerably and important transformations occur to hemodynamics of the cardiovascular system of the fetus. Vascular compliances and resistances as well as the cardiac function show important changes. In order to investigate these modifications, a mathematical approach based on scaling techniques was developed. Vascular and cardiac parameters of the human fetus were related by allometric equations to the anatomical dimensions of vessels that, in turn, depend on the fetal body weight and the gestational age. A scaling factor (b) was identified for each parameter under study: vascular resistances and flow inertances decrease with gestational age (b= -0.33 for flow inertances) whereas vascular compliances remarkably increase (b= 1.33). Scaling factors were also adopted for the fetal cardiac parameters, according to experimental data on the development of fetal myocardium. Parameter values calculated for each week of the last trimester of the fetal gestation, were tested using a mathematical lumped parameter model, previously developed for a human fetus near the term of the gestation. The validation of the scaling method adopted for the parameters was performed by comparing the results of the simulations with a group of data obtained by Doppler velocimetry at different stages of fetal normal gestation. The adopted allometric equations were appropriate in describing the development of the human fetal circulatory system. The ductus venosus, the ductus arteriosus, and the foramen ovale, that conclude their function at the birth moment, as well as the lungs and the brain, do not follow the general growth rate and require different scaling factors.

Computational model of the fluid dynamics in systemic-to-pulmonary shunts.

A systemic-to-pulmonary shunt is a connection created between the systemic and pulmonary arterial circulations in order to improve pulmonary perfusion in children with congenital heart diseases. Knowledge of the relationship between pressure and flow in this new, surgically created, cardiovascular district may be helpful in the clinical management of these patients, whose survival is critically dependent on the blood flow distribution between the pulmonary and systemic circulations. In this study a group of three-dimensional computational models of the shunt have been investigated under steady-state and pulsatile conditions by means of a finite element analysis. The model is used to quantify the effects of shunt diameter (D), curvature, angle, and pulsatility on the pressure-flow (DeltaP-Q) relationship of the shunt. Size of the shunt is the main regulator of pressure-flow relationship. Innominate arterial diameter and angles of insertion have less influence. Curvature of the shunt results in lower pressure drops. Inertial effects can be neglected. The following simplified formulae are derived: DeltaP=(0. 097Q+0.521Q(2))/D(4) and DeltaP=(0.096Q+0.393Q(2))/D(4) for the different shunt geometries investigated (straight and curved shunts, respectively).

Use of mathematical model to predict hemodynamics in cavopulmonary anastomosis with persistent forward flow.

BACKGROUND: The bidirectional cavopulmonary anastomosis with additional pulmonary blood flow is used as a staged procedure or a definitive palliation of univentricular hearts. In this paper the flow competition occurring between the caval and the pulmonary flows is investigated. The hemodynamics in the superior vena cava and the blood flow distribution into the lungs, as well as the systemic arterial oxygen availability, are correlated with the severity of the right ventricle outflow tract obstruction and the pulmonary arteriolar resistance. MATERIALS AND METHODS: Computer models of the pre- and postoperative hemodynamics of univentricular hearts were developed. The effects of increasing severity of the right ventricle outflow tract obstruction, with a pulmonary arteriolar resistance ranging from 0.8 to 7.9 nonindexed Woods units, were simulated. RESULTS: The study indicates that the presence of an additional pulmonary blood flow from the native pulmonary artery may be beneficial. Since an excessive additional blood flow may cause central venous hypertension, its optimal value should be chosen according to the value of pulmonary arteriolar resistance. The model was utilized to simulate four clinical cases. CONCLUSIONS: The simulations show that the model can predict the postoperative hemodynamics and could therefore be usefully applied to predict quantitatively the effect of the native pulmonary blood flow following bidirectional cavopulmonary anastomosis.

Calculating blood flow from Doppler measurements in the systemic-to-pulmonary artery shunt after the Norwood operation: a method based on computational fluid dynamics.

Hypoplastic left heart syndrome is currently the most lethal cardiac malformation of the newborn infant. Survival following a Norwood operation depends on the balance between systemic and pulmonary blood flow, which is highly dependent on the fluid dynamics through the interposition shunt between the two circulations. We used computational fluid dynamic (CFD) models to determine the velocity profile in a systemic-to-pulmonary artery shunt and suggested a simplified method of calculating the blood flow in the shunt based on Doppler measurements. CFD models of systemic-to-pulmonary shunts based on the finite element method were studied. The size of the shunt has been varied from 3 to 5 mm. Velocity profiles at proximal and distal positions were evaluated and correlations between maximum and mean spatial velocity were found. Twenty-one Doppler measurements in the proximal and distal part of the shunt were obtained from six patients with hypoplastic left heart syndrome. Combining Doppler velocities and CFD velocity profiles, blood flow rate in the shunt was calculated. Flow rate evaluated from aortic Doppler and oxygen saturation measurements were performed for comparison. Results showed that proximal shunt Doppler velocities were always greater than the correspondent distal ones (ratio equal to 1.15 +/- 0.11). CFD models showed a similar behaviour (ratio equal to 1.21 +/- 0.03). CFD models gave a V(mean)/V(max) ratio of 0. 480 at the proximal junction and of 0.579 at the distal one. The agreement between the flow evaluated in the proximal and distal areas of the shunt was good (0.576 +/- 0.150 vs. 0.610 +/- 0.166 l/min). Comparison of these data with saturation data and aortic Doppler measurements correlate less well (0.593 +/- 0.156 vs. 1.023 +/- 0.493 l/min). A formula easily to quantify shunt flow rate is proposed. This could be used to evaluate the effects of different therapeutic and pharmacological manoeuvres in this unique circulation.

Computational fluid dynamic simulations of cavopulmonary connections with an extracardiac lateral conduit.

Complex congenital heart defects due to the absence of a ventricular chamber can often be treated by the Fontan surgical procedure. The objective of this work was to quantify the haemodynamics in the Fontan operation (cavopulmonary connection) with extracardiac lateral conduit. Four different models based on the finite element method were constructed with different lengths of inferior anastomosis (range 18-25 mm) and inclinations of the conduit (33 and 47.5 degrees). Mass conservation and Navier-Stokes equations were solved by means of the FIDAP code, based on the finite element method. The left-to-right pulmonary flow ratio and percentage inferior caval blood to the left lung were the highest with the smallest anastomosis and highest inclination: 1.35 and 83.26%, respectively. Dissipated power percentage was higher with the largest anastomosis than with the smallest (19.4 vs 15.8%). It was concluded that, when performing a total cavopulmonary connection, an extracardiac lateral conduit: (i) diverts more flow to the left lung, and (ii) shows higher energy losses when compared with a connection with intra-atrial tunnel. This study could be useful to evaluate the incidence of pulmonary arteriovenous malformations.

The hemodynamic effects of double-orifice valve repair for mitral regurgitation: a 3D computational model.

OBJECTIVES: A 3D computational model has been implemented for the evaluation of the hemodynamics of the double orifice repair. Critical issues for surgical decision making and echo-Doppler evaluation of the results of the procedure are investigated. METHODS: A parametric 3D computational model of the double-orifice mitral valve based on the finite elements model has been constructed from clinical data. Nine different geometries were investigated, corresponding to three total inflow areas (1.5, 2.25 and 3 cm2) and to three orifice configurations (two equal orifices, two orifices of different areas, i.e. one twice as much the other one, and a single orifice). The simulations were performed in transit; the fluid was initially quiescent and was accelerated to the maximum flow rate with a cubic function. For each case, some characteristic values of velocity and pressure were determined: velocities were calculated downstream of each orifice, at the centre of it (Vcen1, Vcen2). The maximum velocity was also determined for each orifice (Vmax1, Vmax2). Maximum pressure drops (deltap(max)) across the valve were compared with the estimations (deltap(Bernoulli)) based on the Bernoulli formula (4 V2). RESULTS: In each simulation, no notable difference was observed between Vcen1 and Vcen2, and between Vmax1 and Vmax2, regardless of the valve configuration. Maximum velocity and deltap(max) were related to the total orifice area and were not influenced by the orifice configuration. Deltap(Bernoulli) calculated with Vmax was well correlated with the deltap(max) obtained throughout the simulations (y = 0.9126x + 0.3464, r = 0.996); on the contrary the pressure drops estimated using Vcen underestimated (y = 0.6757x + 0.3073, r = 0.999) the actual pressure drops. CONCLUSIONS: The hemodynamic behaviour of a double orifice mitral valve does not differ from that of a physiological valve of same total area: pressure drops and flow velocity across the valve are not influenced by the configuration of the valve. Echo Doppler estimation of the maximum velocities is a reliable method for the calculation of pressure gradients across the repaired valve.

Computational fluid dynamic and magnetic resonance analyses of flow distribution between the lungs after total cavopulmonary connection.

Total cavopulmonary connection is a surgical procedure adopted to treat complex congenital malformations of the right heart. It consists basically in a connection of both venae cavae directly to the right pulmonary artery. In this paper a three-dimensional model of this connection is presented, which is based on in vivo measurements performed by means of magnetic resonance. The model was developed by means of computational fluid dynamics techniques, namely the finite element method. The aim of this study was to verify the capability of such a model to predict the distribution of the blood flow into the pulmonary arteries, by comparison with in vivo velocity measurements. Different simulations were performed on a single clinical case to test the sensitivity of the model to different boundary conditions, in terms of inlet velocity profiles as well as outlet pressure levels. Results showed that the flow distribution between the lungs is slightly affected by the shape of inlet velocity profiles, whereas it is influenced by different pressure levels to a greater extent.