Left Ventricular Pressure Waveforms Research Articles

Hemodynamic optimization of cardiac resynchronization therapy by heart sound sensor in pulse generator

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU-HORIZON 2020-International Training Network H2020-MSCA-ITN-2017. Background Continuous ambulatory AV-optimization for Cardiac Resynchronization Therapy (CRT) is mainly performed by electrical means. Objective Develop an estimation model of cardiac function that uses feedback from a piezoelectric transducer embedded in an internal pulse generator to guide CRT optimization. Methods During implantation procedures measurements were performed of left ventricular pressure (LVP) and heart sound waveforms, the latter using the piezoelectric alarm transducer of the device in 22 CRT patients at atrioventricular (AV)-delays of 60-330 ms. Post-hoc, machine learning (ML) was employed to produce models that use heart-sound based features to estimate cardiac function in terms of maximum LVP (LVPmax) and the maximum positive derivative of LVP (LVdP/dtmax). Polynomial curve fitting was used to compare estimated and measured AV-delays with highest LVPmax and LVdP/dtmax. Results The figure displays the concept of the study and an example of the measured and estimated optimization curve. With a dataset of ~30,000 beats, ML provided three most suitable features. Using LVPmax, ML-based estimated optimal AV-delays were not significantly different from measured ones (-5.6 ± 17.1ms for LVPmax and +5.1 ± 46.7ms for LVdP/dtmax). The difference in function between the estimated and measured optimal AV-delays was small and not statically significant (1 ± 3mmHg for LVPmax and 9 ± 57mmHg/s for LVdP/dtmax). Conclusion Heart sound sensors in devices in combination with ML provide a reliable assessment of absolute LVPmax and LVdP/dtmax and may be used for continuous optimization of AV-delays in CRT patients.

Impact of Concomitant Mitral Regurgitation on the Hemodynamic Indicators of Aortic Stenosis.

Background In patients with aortic stenosis (AS), the presence of mitral regurgitation (MR) can lead to underestimation of AS severity and worse clinical outcomes. The objective of this study was to characterize the magnitude of the effects of concomitant MR on hemodynamic indicators of AS severity using clinical data and a computational cardiovascular simulation. Methods and Results Echocardiographic data from 1427 patients with severe AS were used to inform a computational cardiovascular system model, and varying degrees of MR and AS were simulated. Hemodynamic data, including left ventricular and aortic pressure waveforms, were generated for all simulations. Simulated reduction in mean transaortic pressure gradient (MPG) associated with MR was then used to calculate the adjusted MPG in the clinical cohort. MR was present in 861 (60%) patients. Compared with patients without MR, patients with MR had a lower aortic-valve area (0.83±0.2 cm2 versus 0.75±0.2; P<0.001) and were more likely to have a low-gradient pattern (MPG <40 mm Hg) (45% versus 54%; P<0.001). Simulations showed that the presence of concomitant mild, moderate, and severe MR with AS was accompanied by a mean reduction in MPG of 10%, 29%, and 40%, respectively. For patients with MR, their calculated adjusted MPG was on average 24% higher than their MPG (52±22 versus 42±16 mm Hg). Of the 467 patients with low-gradient AS and MR, 240 (51%) would reclassify as high gradient based on their adjusted MPG. Conclusions Concomitant MR results in lower MPG and reduced forward flow compared with isolated AS. Careful quantitation of MR should be factored into the assessment of AS severity to mitigate for potential underestimation.

A noninvasive method of estimating patient-specific left ventricular pressure waveform

Background and objectiveThe left ventricular pressure waveform is indispensable for the construction of the pressure strain loop when investigating coronary artery disease (CAD) patients. In previous studies by others, exclusion of CAD patients has not allowed a reliable estimation of the left ventricular pressure waveform from the pressure strain loop of these patients. To remedy this, we propose a patient-specific noninvasive method for the estimation of left ventricular pressure. MethodsA simplified systemic circulation model consisting primarily of a single fiber model and a 1D simulation of the arterial tree was used. Sensitivity analysis based on the Morris method was performed to select a subset of the important parameters. Following this, the important parameter subset and the set of all the parameters were identified in the model using the pressure waveform of a peripheral artery as input, in a two-step process. In addition, the left ventricular pressure waveform was estimated using the set of all parameters. ResultsReducing the size of the parameter subset significantly decreases the computational cost of parameter optimization in the first step and greatly simplifies the identification of the full parameter set in the second step. Comparison with the reference left ventricular pressure waveform from CAD patients, showed that the proposed method provides a good estimate of the reference left ventricular pressure waveform. The correlation coefficients between the estimated and reference were r = 0.907, r = 0.904 and r = 0.780 for systolic blood pressure, pulse pressure and mean blood pressure, respectively. ConclusionsThis work may provide a convenient surrogate for the estimation of the left ventricular pressure waveform.

A cross-species validation of single-beat metrics of cardiac contractility.

The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross-species study using small and large animals, we comprehensively tested the agreement and validity of multiple single-beat surrogate metrics of LV contractility against the field-standard metrics derived from inferior vena cava occlusion (IVCO). Fifty-six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single-beat metrics of LV contractility. All single-beat metrics were tested for the various underlying assumptions required to be considered a valid metric of cardiac contractility, including load-independency, sensitivity to inotropic stimulation, and ability to diagnose contractile dysfunction in cardiac disease. Of all examined single-beat metrics, only LV maximal pressure normalized to end-diastolic volume (EDV), end-systolic pressure normalized to EDV, and the maximal rate of rise of the LV pressure normalized to EDV showed a moderate-to-excellent agreement with their IVCO-derived reference measure and met all the underlying assumptions required to be considered as a valid cardiac contractile metric in both rodents and large-animal models. Our findings demonstrate that single-beat metrics can be used as a valid, reliable method to quantify cardiac contractile function in basic/preclinical experiments utilizing small- and large-animal models KEY POINTS: Validating and comparing indices of cardiac contractility that avoid caval occlusion would offer considerable advantages for the field of cardiovascular physiology. We comprehensively test the underlying assumptions of multiple single-beat indices of cardiac contractility in rodents and translate these findings to pigs and conscious dogs. We show that when performing caval occlusion is unfeasible, single-beat metrics can be utilized to accurately quantify cardiac inotropic function in basic and preclinical research employing various small and large animal species. We report that maximal left-ventricular(LV)-pressure normalized to end-diastolic volume (EDV), LV end-systolic pressure normalized to EDV and the maximal rate of rise of the LV pressure waveform normalized to EDV are the best three single-beat metrics to measure cardiac inotropic function in both small- and large-animal models.

Validation of non-invasive assessment of myocardial work in aortic stenosis: improvements by modifying the method for estimating the left ventricular pressure waveform

Abstract Introduction Non-invasive myocardial work (MW) index incorporates strain by speckle-tracking echocardiography (STE) and individually estimated left ventricular pressure (LVP) curves to calculate the area of the pressure strain loop without the need for invasive LVP measurements. The method was validated in patients without aortic stenosis (AS) where a reference pressure curve is adjusted for individually measured aortic and mitral valve events and the peak LVP is defined by the brachial artery cuff pressure. Before applying this method in patients with AS, potential limitations which can influence the area of the pressure strain loop, such as the LVP curve profile, correct scaling of peak LVP and correct assessment of aortic events must be addressed. Purpose The present study aimed to assess the impact of the potential limitations specific to patients with AS and thereby the validity of non-invasive MW index in patients with AS. Methods In 20 patients with severe AS we obtained simultaneous LVP, by a micromanometer-tipped catheter, and strain by STE. For each patient, LVP curve estimations were done using three different models: 1. The established LVP reference model based on patients without AS. 2. Enhancement of the established LVP reference model by defining aortic valve opening with diastolic cuff pressure. 3. A new AS specific LVP reference model based on our current invasive measurements. Valvular events were determined by 2D and Doppler echocardiography, and peak LVP estimated as a sum of mean trans-aortic gradient and systolic cuff pressure. Estimated LVP curve tracings were thereafter directly compared with simultaneous invasive measurements (Figure 1). Furthermore, area of the pressure-strain loops using the different estimations of LVP curve were calculated to assess MW and compared to simultaneous invasive measurements for direct comparison. Results All three methods had excellent average correlation coefficient between estimated and invasively measured LVP traces. However, estimations with the AS specific reference curve and those enhanced with incorporation of diastolic pressure for aortic valve opening had a higher correlation coefficient (r=0.99, p&amp;lt;0.001) and a more physiological profile during early systole compared to that of the previously validated reference curve (r=0.96, p&amp;lt;0.001) (Figure 1). Furthermore, there was an excellent correlation (r=0.98, p&amp;lt;0.001) and good agreement between MW calculated with all three non-invasive estimation methods and invasive LVP (Figure 2). Conclusions The present study is the first to confirm the validity of non-invasive MW in patients with AS. Furthermore, a AS specific reference curve and the enhanced reference curve incorporating diastolic cuff pressure to define aortic valve opening both increased the accuracy of the estimated LVP curve and hence estimation of MW. This could be pivotal when assessing AS patients with marked regional differences such as LBBB or regional ischaemia. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Oslo University Hospital Rikshospitalet

In-silico assessment of the effects of right ventricular assist device on pulmonary arterial hypertension using an image based biventricular modeling framework

Pulmonary arterial hypertension (PAH) is a heart disease that is characterized by an abnormally high pressure in the pulmonary artery (PA). While right ventricular assist device (RVAD) has been considered recently as a treatment option for end-stage PAH patients, its effects on biventricular mechanics are, however, largely unknown. To address this issue, we developed an image-based modeling framework consisting of a biventricular finite element (FE) model that is coupled to a lumped model describing the pulmonary and systemic circulations in a closed-loop system. The biventricular geometry was reconstructed from the magnetic resonance images of two PAH patients showing different degree of RV remodeling and a normal subject. The framework was calibrated to match patient-specific measurements of the left ventricular (LV) and RV volume and pressure waveforms. An RVAD model was incorporated into the calibrated framework and simulations were performed with different pump speeds. Results showed that RVAD unloads the RV, improves cardiac output and increases septum curvature, which are more pronounced in the PAH patient with severe RV remodeling. These improvements, however, are also accompanied by an adverse increase in the PA pressure. These results suggest that the RVAD implantation may need to be optimized depending on disease progression.

Clinical implication of right-sided augmentation pressure in patients with pulmonary hypertension.

Similar to left ventricular and aortic pressure waveforms, augmentation pressure (AugPr) in the right ventricular (RV) pressure waveform is also frequent in patients with pulmonary hypertension (PH). This study sought to evaluate whether the degree of AugPr in RV pressure waveform has prognostic value. Forty-one patients (13 men; mean age = 50.7 ± 16.1 years) with group 1 PH (mean pulmonary artery pressure [mPAP] ≥ 25 mmHg) who underwent cardiac catheterization as part of their work-up were retrospectively enrolled. Patients were divided into three groups. Group A: AugPr/RV systolic pressure < 25%; group B: AugPr/RV systolic pressure ≥ 25%; and group C: no discernible AugPr but showing peaked RV pressure waveform. Ten patients were included in group A (male-to-female ratio 3:7; mean age = 45.9 ± 12.1 years), 12 in group B (4:8, 53.8 ± 14.6 years), and 19 in group C (6:13, 51.8 ± 18.7 years). No differences in mPAP were seen between the three groups. Pulse pressure was significantly higher in group C compared to group A. Eight patients died during the mean follow-up period of 35.9 ± 30.7 months; the incidence of death was significantly higher in group C than in the other groups (one patient in group A and seven patients in group C). AugPr in RV pressure waveform has prognostic value in patients with PH. Therefore, additional attention should be given to the RV pressure waveform in patients with PH undergoing invasive pressure measurements as a part of their work-up.

Gradient variability in hypertrophic cardiomyopathy: New insights from computer‐assisted, high fidelity, rest and exercise hemodynamic analysis

ObjectivesThis study examines the intrapatient variability in peak instantaneous left ventricular outflow tract (LVOT) gradients and aortic pulse pressures during rest, exercise, and after ventricular ectopy.BackgroundAlthough the variability in LVOT gradients in patients with hypertrophic cardiomyopathy (HCM) is well known, the predictors of such variation are not. We hypothesized that quantitative invasive analysis of gradient variation could identify useful predictors of maximal gradients.MethodsVariability in continuously recorded, high‐fidelity left ventricular and aortic pressure waveforms were evaluated by computer‐assisted analysis in the resting state (N = 659 beats) and during supine exercise (N = 379 beats) in a symptomatic patient with a resting LVOT gradient >30 mmHg and frequent ventricular ectopy.ResultsAt rest, the peak left ventricular and aortic pressures at the time of the peak instantaneous LVOT gradient for all sinus and postectopic beats followed consistent regression slopes characterizing the potential energy loss between the LV cavity and aorta. During exercise, similar regression slopes were identified, and these converged with the resting slopes at the point of the maximal measured LVOT gradient. Component analysis of the LVOT gradient suggests that resting beat‐to‐beat variability provides information similar to post‐ectopic pressures for predicting maximal gradients in obstructive‐variant HCM.ConclusionsOur study suggests that computer‐assisted analysis of hemodynamic variability in HCM may prove useful in characterizing the severity of obstruction. Further study is warranted to confirm the reproducibility and utility of this finding in a population with clinically significant exercise‐induced gradients.

Abstract 16664: Intrapatient Variability in the Brockenbrough-Braunwald-Morrow Sign and Peak Instantaneous Left Ventricular Outflow Gradients in Obstructive Hypertrophic Cardiomyopathy

Introduction: Although the variability in left ventricular outflow tract (LVOT) gradients in patients with hypertrophic cardiomyopathy (HCM) is well known, the value of pulse pressure (PP) changes with ectopy for predicting changes in LVOT gradient remains unreported. Hypothesis: This study examines the intrapatient variability in peak instantaneous LVOT gradients and aortic pulse pressure (PP) associated with the Brockenbrough-Braunwald-Morrow sign (BBM sign) compared with beat-to-beat variability. Methods: Variability in continuously recorded, high-fidelity left ventricular and aortic pressure waveforms were evaluated by computer-aided analysis in the resting state (N = 659 beats) and during supine exercise (N = 379 beats) in a symptomatic patient with a resting LVOT gradient &gt;30 mmHg. Results: BBM sign was observed in 92.9% (26/28) of post-PVC beats at rest and the post PVC PP decreased 11.8±8.2% (P&lt;0.001) compared with a 148.3±49.5% (P&lt;0.001) increase in the LVOT gradient. During exercise, BBM sign was noted in 84.2% (32/38) of post-PVCs beats and PP decreased 4.0±6.3% (P&lt;0.001) compared with a 74.2±37.5% (P&lt;0.001) increase in LVOT gradient. PP decreases were also noted in 89.5% (17/19) beats during sinus arrhythmia following prolonged RR intervals. Changes in pulse pressure with ectopy poorly predicted quantitative changes in the LVOT gradient (R 2 ≤ 0.198). However, component analysis of the LVOT gradient suggests that beat-to-beat variability provides information similar to ectopic provocation in characterizing gradients in HCM and that rest and exercise changes converge to a common reference value. Conclusions: Although caution is suggested when interpreting pulse pressure changes with the BBM sign as surrogate for measuring LVOT gradients, this study suggests that analysis of hemodynamic variability in HCM may prove useful in characterizing the severity of obstruction.

Novel echocardiographic method to assess left ventricular chamber stiffness and elevated end-diastolic pressure based on time-velocity integral measurements of pulmonary venous and transmitral flows.

The detection of increased left ventricular (LV) chamber stiffness may play an important role in assessing cardiac patients with potential but not overt heart failure. A non-invasive method to estimate it is not established. We investigated whether the echocardiographic backward/forward flow volume ratio from the left atrium (LA) during atrial contraction reflects the LV chamber stiffness. We studied 62 patients who underwent cardiac catheterization and measured their left ventricular end-diastolic pressure (LVEDP) and pressure increase during atrial contraction (ΔPa) from the LV pressure waveform. Using the echocardiographic biplane method of disks, we measured the LV volume change during atrial contraction indexed to the body surface area (ΔVa), and ΔPa/ΔVa was calculated as a standard for the LV operating chamber stiffness. Using pulsed Doppler echocardiography, we measured the time-velocity integral (TVI) of the backward pulmonary venous (PV) flow during atrial contraction (IPVA) and the ratio of IPVA to the PV flow TVI throughout a cardiac cycle (FPVA). We also measured the TVI of the atrial systolic forward transmitral flow (IA) and the ratio of the IA to the transmitral TVI during a cardiac cycle (FA) and calculated IPVA/IA and FPVA/FA. IPVA/IA and FPVA/FA were well correlated with ΔPa/ΔVa (r = 0.79 and r = 0.81) and LVEDP (r = 0.73 and r = 0.77). The areas under the ROC curve to discriminate LVEDP >18 mmHg were 0.90 for IPVA/IA and 0.93 for FPVA/FA. The FPVA/FA, the backward/forward flow volume ratio from the LA during atrial contraction, is useful for non-invasive assessments of LV chamber stiffness and elevated LVEDP.

Beat-by-Beat Estimation of the Left Ventricular Pressure-Volume Loop Under Clinical Conditions.

This paper develops a method for the minimally invasive, beat-by-beat estimation of the left ventricular pressure-volume loop. This method estimates the left ventricular pressure and volume waveforms that make up the pressure-volume loop using clinically available inputs supported by a short, baseline echocardiography reading. Validation was performed across 142,169 heartbeats of data from 11 Piétrain pigs subject to two distinct protocols encompassing sepsis, dobutamine administration and clinical interventions. The method effectively located pressure-volume loops, with low overall median errors in end-diastolic volume of 8.6%, end-systolic volume of 17.3%, systolic pressure of 19.4% and diastolic pressure of 6.5%. The method further demonstrated a low overall mean error of 23.2% predicting resulting stroke work, and high correlation coefficients along with a high percentage of trend compass 'in band' performance tracking changes in stroke work as patient condition varied. This set of results forms a body of evidence for the potential clinical utility of the method. While further validation in humans is required, the method has the potential to aid in clinical decision making across a range of clinical interventions and disease state disturbances by providing real-time, beat-to-beat, patient specific information at the intensive care unit bedside without requiring additional invasive instrumentation.

Simulating the Dynamics of an Aortic Valve Prosthesis in a Pulse Duplicator: Numerical Methods and Initial Experience.

Each year, approximately 250,000 surgical procedures are performed to repair or to replace cardiac valves [1], and of these, approximately 50,000 are aortic valve replacement operations. Despite decades of development, many of the limitations of cardiac valve prostheses remain consequences of the fluid dynamics generated by the replacement valve [1]. To enable cross-validation studies that allow for detailed comparisons of experimental and computational results, we are developing fluid-structure interaction (FSI) models of the dynamics of aortic valve prostheses mounted in a ViVitro Systems, Inc. pulse duplicator apparatus. Such an experimentally validated computational model promises both to facilitate the design of novel valve prostheses, and also to assist in the regulatory process, by providing access to detailed spatially- and temporally-resolved flow data that are challenging to obtain via experimental approaches.Our numerical approach to FSI is based on the immersed boundary (IB) method [2]. The structural dynamics are described in Lagrangian form using a material coordinate system, whereas the momentum of the fluid-solid system and the viscosity and incompressibility of the fluid are described in Eulerian form using fixed Cartesian physical coordinates. Lagrangian and Eulerian variables are coupled by integral transforms with Dirac delta function kernels. When the equations are discretized, the singular delta function is replaced by a regularized version of the delta function. See Peskin [2] for details.To treat rigid body dynamics within the framework of the IB method, we adopt an approach similar to that recently developed by Kim and Peskin [3], in which the continuous equations are:(1)ρ(∂u∂t(x,t)+u(x,t)·∇u(x,t)) =-∇p(x,t)+μ∇2u(x,t)+f(x,t)(2)∇·u(x,t)=0(3)f(x,t)=∫UF(s,t)δ(x-X(s,t))ds(4)∂X∂t(s,t)=∫Ωu(x,t)δ(x-X(s,t))dx(5)∂Y∂t(s,t)=V(t)+W(t)×R(s,t)(6)F(s,t)=κ(Y(s,t)-X(s,t))in which x∈Ω are physical coordinates, s∈U are material coordinates, X(s,t) and Y(s,t) are time-dependent mappings from material coordinates to current coordinates, u(x,t) is the Eulerian velocity field, p(x,t) is the Eulerian pressure field, f(x,t) and F(s,t) are equivalent Eulerian and Lagrangian force densities, ρ is the fluid density, μ is the fluid viscosity, and δ(x)=δ(x)δ(y)δ(z) is the three-dimensional Dirac delta function. The force field F(s,t) acts to impose the rigidity constraint ∂X∂t(s,t)=U(s,t)=V(t)+W(t)×R(s,t)in which V(t) and W(t) are respectively the linear and angular velocity of the structure and R(s,t) is the radius vector. In the limit κ→∞, the constraint is imposed exactly; for finite κ&gt;0, the constraint is only approximately satisfied. The dynamics of V(t) and W(t) are determined from the requirement that the time rate of change of the “excess” linear and angular momentum (i.e., in excess of the momentum accounted for by the momentum equation (1)) be proportional to the net force ∫Ω-F(s,t)ds and net torque ∫Ω-F(s,t)×R(s,t)ds acting on the body.Geometrical models of the aortic section of the ViVitro pulse duplicator and of a St. Jude Regent valve were created using SolidWorks (Dassault Systèmes SolidWorks Corp., Waltham, MA). These geometrical models were meshed using CUBIT (Sandia National Laboratory, Albuquerque, NM). To drive flow through the valve, we impose a physiological left ventricular pressure waveform, and characteristic downstream compliance and resistance to mimic the response of the systemic circulation. Simulations used the IBAMR software [4]. Initial simulation results are shown in Fig. 1, demonstrating that realistic flow rates can be obtained using this model under realistic driving and loading conditions. We are presently fine tuning this model in preparation for validation studies.We acknowledge discussions with A. P. S. Bhalla, A. Donev, D. M. McQueen, and C. S. Peskin, and funding from AHA award 10SDG4320049, NIH award HL117063, and NSF awards DMS 1016554 and OCI 1047734.

A Novel Methodology to Measure Serial Changes in Left Ventricular Pressure in Ambulatory Canines After Heart Failure Induction and Neuromodulatory Therapy

Background A novel technique to measure hemodynamic function in ambulatory canines was used to quantify serial changes in left ventricular hemodynamic function after myocardial infarction (MI), pacing-induced heart failure (HF), and treatment with spinal cord stimulation (SCS). Methods Telemetric devices were implanted into 6 canines to continuously measure left ventricular pressure (LVP) in freely moving ambulatory canines. Data were collected for 1 day in each of the following stages: baseline (6 canines), 7 days after foam embolization of the left anterior descending artery to induce MI (4 canines), and 1 day after high-rate right ventricular pacing to induce HF (3 canines). Left ventricular end-diastolic pressure (LVEDP) and max positive and negative dP/dt were extracted from LVP waveforms for 10-minute intervals over each hour of the day to produce a daily mean. Left ventricular ejection fraction (LVEF) was also obtained using echocardiography at baseline and after HF. Results Results are presented in the table. LVEDP, +dP/dt, and –dP/dt were not significantly changed after MI. However, these parameters were significantly changed after HF. In 2 animals, 5 weeks of therapy with SCS restored +dP/dt (1780 mm Hg/s) and –dP/dt (–1666 mm Hg/s) to baseline levels. Tabled 1 Treatment P value Parameter Baseline MI HF Baseline to MI MI to HF Baseline to HF LVEDP (mm Hg) 5 ± 2 4 ± 4 25 ± 24 .671 .14 .067 +dP/dt (mm Hg/s) 1907 ± 202 1970 ± 314 1189 ± 294 .716 .021* .0033* -dP/dt (mm Hg/s) -1659 ± 97 -1708 ± 36 -1275 ± 286 .372 .027* .017* LVEF (%) 58 ± 5 — 22 ± 2 — — .00002* *Statistical significance indicated by P <.05. Open table in a new tab Conclusions HF reduces LVEF, ±dP/dt, and LVEDP compared with baseline. HF also reduces ±dP/dt compared with post-MI. Infarction has no impact on LVEDP or ±dP/dt. In 2 canines, SCS normalized LVP hemodynamics. A novel technique to measure hemodynamic function in ambulatory canines was used to quantify serial changes in left ventricular hemodynamic function after myocardial infarction (MI), pacing-induced heart failure (HF), and treatment with spinal cord stimulation (SCS). Telemetric devices were implanted into 6 canines to continuously measure left ventricular pressure (LVP) in freely moving ambulatory canines. Data were collected for 1 day in each of the following stages: baseline (6 canines), 7 days after foam embolization of the left anterior descending artery to induce MI (4 canines), and 1 day after high-rate right ventricular pacing to induce HF (3 canines). Left ventricular end-diastolic pressure (LVEDP) and max positive and negative dP/dt were extracted from LVP waveforms for 10-minute intervals over each hour of the day to produce a daily mean. Left ventricular ejection fraction (LVEF) was also obtained using echocardiography at baseline and after HF. Results are presented in the table. LVEDP, +dP/dt, and –dP/dt were not significantly changed after MI. However, these parameters were significantly changed after HF. In 2 animals, 5 weeks of therapy with SCS restored +dP/dt (1780 mm Hg/s) and –dP/dt (–1666 mm Hg/s) to baseline levels. *Statistical significance indicated by P <.05. HF reduces LVEF, ±dP/dt, and LVEDP compared with baseline. HF also reduces ±dP/dt compared with post-MI. Infarction has no impact on LVEDP or ±dP/dt. In 2 canines, SCS normalized LVP hemodynamics.

Immersed boundary model of aortic heart valve dynamics with physiological driving and loading conditions.

The immersed boundary (IB) method is a mathematical and numerical framework for problems of fluid–structure interaction, treating the particular case in which an elastic structure is immersed in a viscous incompressible fluid. The IB approach to such problems is to describe the elasticity of the immersed structure in Lagrangian form, and to describe the momentum, viscosity, and incompressibility of the coupled fluid–structure system in Eulerian form. Interaction between Lagrangian and Eulerian variables is mediated by integral equations with Dirac delta function kernels. The IB method provides a unified formulation for fluid–structure interaction models involving both thin elastic boundaries and also thick viscoelastic bodies. In this work, we describe the application of an adaptive, staggered-grid version of the IB method to the three-dimensional simulation of the fluid dynamics of the aortic heart valve. Our model describes the thin leaflets of the aortic valve as immersed elastic boundaries, and describes the wall of the aortic root as a thick, semi-rigid elastic structure. A physiological left-ventricular pressure waveform is used to drive flow through the model valve, and dynamic pressure loading conditions are provided by a reduced (zero-dimensional) circulation model that has been fit to clinical data. We use this model and method to simulate aortic valve dynamics over multiple cardiac cycles. The model is shown to approach rapidly a periodic steady state in which physiological cardiac output is obtained at physiological pressures. These realistic flow rates are not specified in the model, however. Instead, they emerge from the fluid–structure interaction simulation.

DEVELOPMENT OF IMPLANTABLE FLOW-THROUGH LEFT VENTRICULAR PRESSURE TELEMETRIC TRANSMITTER FOR SMALL RODENT ANIMALS: PP.14.31

Objective: Although 24-hour arterial blood pressure can be monitored in a free-moving animal using pressure telemetric transmitter mostly from Data Science International (DSI), accurate monitoring of 24-hour mouse left ventricular pressure (LVP) is not available because of its insufficient frequency response to a high frequency signal such as the maximum derivative of mouse LVP (LVdP/dtmax and LVdP/dtmin). The aim of the study was to develop a tiny implantable flow-through LVP telemetric transmitter for small rodent animals, which can be potentially adapted for human 24 hour BP and LVP accurate monitoring. Design and Method: The mouse LVP telemetric transmitter (Diameter: ∼12 mm, ∼0.4 g) was assembled by a pressure sensor, a passive RF telemetry chip, and to a 1.2F Polyurethane (PU) catheter tip. The device was developed in two configurations and compared with existing DSI system: (a) prototype-I: a new flow-through pressure sensor with wire link and (b) prototype-II: prototype-I plus a telemetry chip and its receiver. All the devices were applied in C57BL/6J mice. Data are mean ± SEM. Results: A high frequency response (>100 Hz) PU heparin saline-filled catheter was inserted into mouse left ventricle via right carotid artery and implanted, LV systolic pressure (LVSP), LVdP/dtmax, and LVdP/dtmin were recorded on day2, 3, 4, 5, and 7 in conscious mice. The hemodynamic values were consistent and comparable (139 ± 4 mmHg, 16634 ± 319, -12283 ± 184 mmHg/s, n = 5) to one recorded by a validated Pebax03 catheter (138 ± 2mmHg, 16045 ± 443 and -12112 ± 357 mmHg/s, n = 9). Similar LV hemodynamic values were obtained with Prototype-I. The same LVP waveforms were synchronically recorded by Notocord wire and Senimed wireless software through prototype-II in anesthetized mice. Conclusion: An implantable flow-through LVP transmitter (prototype-I) is generated for LVP accurate assessment in conscious mice. The prototype-II needs a further improvement on data transmission bandwidth and signal coupling distance to its receiver for accurate monitoring of LVP in a free-moving mouse.

A Tissue-Level Electromechanical Model of the Left Ventricle: Application to the Analysis of Intraventricular Pressure

The ventricular pressure profile is characteristic of the cardiac contraction progress and is useful to evaluate the cardiac performance. In this contribution, a tissue-level electromechanical model of the left ventricle is proposed, to assist the interpretation of left ventricular pressure waveforms. The left ventricle has been modeled as an ellipsoid composed of twelve mechano-hydraulic sub-systems. The asynchronous contraction of these twelve myocardial segments has been represented in order to reproduce a realistic pressure profiles. To take into account the different energy domains involved, the tissue-level scale and to facilitate the building of a modular model, multiple formalisms have been used: Bond Graph formalism for the mechano-hydraulic aspects and cellular automata for the electrical activation. An experimental protocol has been defined to acquire ventricular pressure signals from three pigs, with different afterload conditions. Evolutionary Algorithms have been used to identify the model parameters in order to minimize the error between experimental and simulated ventricular pressure signals. Simulation results show that the model is able to reproduce experimental ventricular pressure. In addition, electro-mechanical activation times have been determined in the identification process. For example, the maximum electrical activation time is reached, respectively, 96.5, 139.3 and 131.5 ms for the first, second, and third pigs. These preliminary results are encouraging for the application of the model on non-invasive data like ECG, arterial pressure or myocardial strain.

Pilot study of chronic direct monitoring of left ventricular pressure using an implantable device in heart failure patients

Aims: Continuous, long term monitoring of filling pressures may be useful in the management of heart failure. There are reports of chronic implantable diagnostic devices that track right-sided pressures as a means of estimating left sided ones. However, right-sided pressures may not provide accurate and sensitive measures, as they are indirect estimations of left sided pressures, separated by a variable pulmonary resistance. This pivotal LVP-HF study addresses early feasibility of directly measuring left sided pressures, using an implantable sensor that samples left ventricular pressure (LVP). Methods: NYHA Class III and IV heart failure patients undergoing cardiac surgery were included in the study. The sensor was placed epicardially, and includes a fluid filled, 28mm, 6F catheter that is disposed transmyocardially to sample the intracardiac LVP at 500Hz. LVP waveforms are being transmitted via the internet for remote viewing and analysis. Results: Between September 2006 and May 2007 eight patients were included, (5 CABG, 2 CABG + MVR, 1 AVR). Mean EF was 27%, there was no mortality and all patients are currently alive. Longest follow-up is 12 months and no device related adverse events have been observed. Respiratory variation and aortic reflections are evident in the traces of left ventricular pressure. Conclusions: For the first time continuous, remote monitoring of intracardiac left ventricular pressures using an implanted sensor has been demonstrated in humans as a safe and feasible option to allow assessment of left ventricular function. Further follow-up and studies may confirm the findings of this pivotal study.

Development of “Plug and Play” TransApical to Aorta VAD

Our TransApical to Aorta pump, a simple and minimally invasive left ventricular (LV) assist device, has a flexible, thin-wall conduit connected by six struts to a motor with ball bearings and a turbine extending into the blood path. Pulsatile flow is inherent in the design as the native heart contraction preloads the turbine. In six healthy sheep, the LV apex was exposed by a fifth intercostal left thoracotomy. The pump was inserted from the cardiac apex through the LV cavity into the ascending aorta. Aortic and LV pressure waveforms, pump flow, motor current, and pressure were directly measured. All six cannula pumps were smoothly advanced on the first attempt. Pump implantation was <15 minutes (13.6 +/- 1.8 minutes). Blood flow was 2.8 l/min to 4.4 l/min against 86 +/- 8.9 mm Hg mean arterial blood pressure at maximum flow. LV systemic pressure decreased significantly from 102.5 +/- 5.55 mm Hg to 58.8 +/- 15.5 mm Hg at the fourth hour of pumping (p = 0.042), and diastolic LV pressure decreased from 8.4 +/- 3.7 to 6.1 +/- 2.3 mm Hg (p > 0.05). The pump operated with a current of 0.4 to 0.7 amps and rotation speed of 28,000 to 33,000 rpm. Plasma free hemoglobin was 4 +/- 1.41 mg/dl (range, 2 to 5 mg/dl) at termination. No thrombosis was observed at necropsy.A left ventricular assist device using the transapical to aorta approach is quick, reliable, minimally invasive, and achieves significant LV unloading with minimal blood trauma.

The assessment of acute load and contractility changes by left ventricular pressure measurements

The aim of this study was to establish whether analysis of the left ventricular pressure waveform provides indicative information about cardiac load and contractility and to develop an algorithm for computer-based assessment of changes in these variables. In eight healthy standard breed anaesthetized open-chest pigs, a high frequency response guide-wire mounted pressure sensor was introduced into the left ventricle. Preload reduction was induced by vena cava occlusion, afterload increase by an i.v. injection of phenylephrine and increased contractility by an i.v. injection of adrenalin. Left ventricular pressure waveform analysis was performed by plotting the slope of the pressure curve during the systolic ejection period versus maximal systolic pressure. The analysis revealed characteristic changes in left ventricular pressure and pressure waveform and identified easily discernible reaction patterns in the slope versus maximal pressure plot, specific for each provocation. Analysis of the left ventricular waveform provides indicative information about loading conditions and contractility. The proposed algorithm can easily be implemented in pressure monitoring systems allowing real-time assessment and discrimination of acute changes in preload, afterload and myocardial performance.

Noninvasive measurement of isovolumetric contraction time by Doppler cardiography can be substituted for fetal cardiac contractility: Evaluation of a fetal lamb study

Objective The objective of this study is to clarify whether the isovolumetric contraction time obtained from Doppler cardiography (Doppler ICT) can be an index substituted for fetal cardiac contractility. Materials and methods In 10 pregnant ewes, fetal hypoxemia was induced by giving a variable mixture of gases. Through experiment, the Doppler ICT, pre-ejection period (PEP), and the maximum first derivative of the left ventricular pressure waveform (Max d p/d t) were simultaneously recorded every 10 min. The relationship between both the Doppler ICT and PEP, and the Max d p/d t were analyzed. Results A significant negative linear regression was founded between the Doppler ICT and the Max d p/d t. A significant negative linear regression was also shown between PEP and the Max d p/d t. Moreover, the regression of Max d p/d t on ICT had significantly less residual variance than the regression of Max d p/d t on PEP ( p = 0.0004). Conclusion In contrast to PEP, Doppler ICT is a reliable, and non-invasive index which can be substituted for fetal cardiac contractility.