Guruprasad A. Giridharan

Characterization of an Adult Mock Circulation for Testing Cardiac Support Devices

A need exists for a mock circulation that behaves in a physiologic manner for testing cardiac devices in normal and pathologic states. To address this need, an integrated mock cardiovascular system consisting of an atrium, ventricle, and systemic and coronary vasculature was developed specifically for testing ventricular assist devices (VADs). This test configuration enables atrial or ventricular apex inflow and aortic outflow cannulation connections. The objective of this study was to assess the ability of the mock ventricle to mimic the Frank–Starling response of normal, heart failure, and cardiac recovery conditions. The pressure–volume relationship of the mock ventricle was evaluated by varying ventricular volume over a wide range via atrial (preload) and aortic (afterload) occlusions. The input impedance of the mock vasculature was calculated using aortic pressure and flow measurements and also was used to estimate resistance, compliance, and inertial mechanical properties of the circulatory system. Results demonstrated that the mock ventricle pressure–volume loops and the end diastolic and end systolic pressure–volume relationships are representative of the Starling characteristics of the natural heart for each of the test conditions. The mock vasculature can be configured to mimic the input impedance and mechanical properties of native vasculature in the normal state. Although mock circulation testing systems cannot replace in vivo models, this configuration should be well suited for developing experimental protocols, testing device feedback control algorithms, investigating flow profiles, and training surgical staff on the operational procedures of cardiovascular devices.

Cavopulmonary assist for the univentricular Fontan circulation: Von Kármán viscous impeller pump

OBJECTIVE In a univentricular Fontan circulation, modest augmentation of existing cavopulmonary pressure head (2-5 mm Hg) would reduce systemic venous pressure, increase ventricular filling, and thus substantially improve circulatory status. An ideal means of providing mechanical cavopulmonary support does not exist. We hypothesized that a viscous impeller pump, based on the von Kármán viscous pump principle, is optimal for this role. METHODS A 3-dimensional computational model of the total cavopulmonary connection was created. The impeller was represented as a smooth 2-sided conical actuator disk with rotation in the vena caval axis. Flow was modeled under 3 conditions: (1) passive flow with no disc; (2) passive flow with a nonrotating disk, and (3) induced flow with disc rotation (0-5K rpm). Flow patterns and hydraulic performance were examined for each case. Hydraulic performance for a vaned impeller was assessed by measuring pressure increase and induced flow over 0 to 7K rpm in a laboratory mock loop. RESULTS A nonrotating actuator disc stabilized cavopulmonary flow, reducing power loss by 88%. Disk rotation (from baseline dynamic flow of 4.4 L/min) resulted in a pressure increase of 0.03 mm Hg. A further increase in pressure of 5 to 20 mm Hg and 0 to 5 L/min flow was obtained with a vaned impeller at 0 to 7K rpm in a laboratory mock loop. CONCLUSIONS A single viscous impeller pump stabilizes and augments cavopulmonary flow in 4 directions, in the desired pressure range, without venous pathway obstruction. A viscous impeller pump applies to the existing staged protocol as a temporary bridge-to-recovery or -transplant in established univentricular Fontan circulations and may enable compressed palliation of single ventricle without the need for intermediary surgical staging or use of a systemic-to-pulmonary arterial shunt.

Hemodynamic responses to continuous versus pulsatile mechanical unloading of the failing left ventricle.

Debate exists regarding the merits and limitations of continuous versus pulsatile flow mechanical circulatory support. To characterize the hemodynamic differences between each mode of support, we investigated the acute effects of continuous versus pulsatile unloading of the failing left ventricle in a bovine model. Heart failure was induced in male calves (n = 14). During an acute study, animals were instrumented through thoracotomy for hemodynamic measurement. A continuous flow (n = 8) and/or pulsatile flow (n = 8) left ventricular assist device (LVAD) was implanted and studied during maximum support (∼5 L/min) and moderate support (∼2–3 L/min) modes. Pulse pressure (PP), surplus hemodynamic energy (SHE), and (energy equivalent pressure [EEP]/mean aortic pressure (MAP) − 1) × 100% were derived to characterize hemodynamic energy profiles during the different support modes. Standard hemodynamic parameters of cardiac performance were also derived. Data were analyzed by repeated measures one-way analysis of variance within groups and unpaired Students t-tests across groups. During maximum and moderate continuous unloading, PP, SHE, and (EEP/MAP − 1) × 100% were significantly decreased compared with baseline and compared with pulsatile unloading. As a result, continuous unloading significantly altered left ventricular peak systolic pressure, aortic systolic and diastolic pressure, ±dP/dt, and rate × pressure product, whereas pulsatile unloading preserved a normal profile of physiologic values. As continuous unloading increased, the pressure-volume relationship collapsed, and the aortic valve remained closed. In contrast, as pulsatile unloading increased, a comparable decrease in left ventricular volumes was noted. However, a normal range of left ventricular pressures was preserved. Continuous unloading deranged the physiologic profile of myocardial and vascular hemodynamic energy utilization, whereas pulsatile unloading preserved more normal physiologic values. These findings may have important implications for chronic LVAD therapy.

Modeling and control of a brushless DC axial flow ventricular assist device.

This article presents an integrated model of the human circulatory system that incorporates circulatory support by a brushless DC axial flow ventricular assist device (VAD), and a feedback VAD controller designed to maintain physiologically sufficient perfusion. The developed integrated model combines a network type model of the circulatory system with a nonlinear dynamic model of the brushless DC pump. We show that maintaining a reference differential pressure between the left ventricle and aorta leads to adequate perfusion for different pathologic cases, ranging from normal heart to left heart asystole, and widely varying physical activity scenarios from rest to exercise.

Microfluidic cardiac cell culture model (μCCCM).

Physiological heart development and cardiac function rely on the response of cardiac cells to mechanical stress during hemodynamic loading and unloading. These stresses, especially if sustained, can induce changes in cell structure, contractile function, and gene expression. Current cell culture techniques commonly fail to adequately replicate physical loading observed in the native heart. Therefore, there is a need for physiologically relevant in vitro models that recreate mechanical loading conditions seen in both normal and pathological conditions. To fulfill this need, we have developed a microfluidic cardiac cell culture model (μCCCM) that for the first time allows in vitro hemodynamic stimulation of cardiomyocytes by directly coupling cell structure and function with fluid induced loading. Cells are cultured in a small (1 cm diameter) cell culture chamber on a thin flexible silicone membrane. Integrating the cell culture chamber with a pump, collapsible pulsatile valve and an adjustable resistance element (hemostatic valve) in series allow replication of various loading conditions experienced in the heart. This paper details the design, modeling, fabrication and characterization of fluid flow, pressure and stretch generated at various frequencies to mimic hemodynamic conditions associated with the normal and failing heart. Proof-of-concept studies demonstrate successful culture of an embryonic cardiomyoblast line (H9c2 cells) and establishment of an in vivo like phenotype within this system.

Accurate Automatic Analysis of Cardiac Cine Images

Acquisition of noncontrast agent cine cardiac magnetic resonance (CMR) gated images through the cardiac cycle is, at present, a well-established part of examining cardiac global function. However, regional quantification is less well established. We propose a new automated framework for analyzing the wall thickness and thickening function on these images that consists of three main steps. First, inner and outer wall borders are segmented from their surrounding tissues with a geometric deformable model guided by a special stochastic speed relationship. The latter accounts for Markov-Gibbs shape and appearance models of the object-of-interest and its background. In the second step, point-to-point correspondences between the inner and outer borders are found by solving the Laplace equation and provide initial estimates of the local wall thickness and the thickening function index. Finally, the effects of the segmentation error is reduced and a continuity analysis of the LV wall thickening is performed through iterative energy minimization using a generalized Gauss-Markov random field (GGMRF) image model. The framework was evaluated on 26 datasets from clinical cine CMR images that have been collected from patients with eleven independent studies, with chronic ischemic heart disease and heart damage. The performance evaluation of the proposed segmentation approach, based on the receiver operating characteristic (ROC) and Dice similarity coefficients (DSC) between manually drawn and automatically segmented contours, confirmed a high robustness and accuracy of the proposed segmentation approach. Furthermore, the Bland-Altman plot is used to assess the limit of agreement of our measurements of the global function parameters compared to the ground truth. Importantly, comparative results on the publicly available database (MICCAI 2009 Cardiac MR Left Ventricle Segmentation) demonstrated a superior performance of the proposed segmentation approach over published methods.

Intraoperative Evaluation of the HeartMate II Flow Estimator

BACKGROUND Direct measurement of blood flow output has been incorporated into ventricular assist devices (VADs), but long-term reliability of the additional device components has raised concerns regarding sensor drift and failure. As an alternative approach, the HeartMate II axial VAD (Thoratec Corp, Pleasanton, CA) estimates device flow output from power consumption and rotational speed of the device motor. This study evaluated the accuracy of HeartMate II flow estimation at the time of implantation. METHODS In 20 patients, intraoperative blood flow measurement of the HeartMate II flow estimator was compared with flow values obtained with an ultrasonic flow probe placed around the device outflow graft. Estimated and measured VAD flow data were simultaneously recorded and digitally stored while the device motor speed varied from 7,800 to 11,000 rpm and while achieving device flow outputs of 2 to 7 liters/min. Estimated and measured flows were compared using linear regression analyses and root mean square error. RESULTS HeartMate II flow estimation (FE) demonstrated a linear correlation with ultrasonic flow probe (FP) measurements: FE = 0.74 FP + 0.99 (R(2) = 0.56, p = 0.0001). A root mean square error of 0.8 liters/min was observed between flow estimation and direct flow measurement and suggests a 15% to 20% difference at flows of 4 of 6 liters/min. CONCLUSIONS These results suggest that HeartMate II flow estimation may be used to provide directional information for trend purposes rather than absolute values of device blood flow output. Patient management should include but not be limited to this information.

Cavopulmonary Assist: (Em)powering the Univentricular Fontan Circulation

Since the Fontan/Kreutzer procedure was introduced, evolutionary clinical advances via a staged surgical reconstructive approach have markedly improved outcomes for patients with functional single ventricle. However, significant challenges remain. Early stage mortality risk seems impenetrable. Serious morbidities - construed as immutable consequences of palliation - have hardly been addressed. Late functional status is increasingly linked to pathophysiologic consequences of prior staged procedures. As more single-ventricle patients survive into adulthood, Fontan failure is emerging as an intractable problem for which there is no targeted therapy. Incremental solutions to address these ongoing problems have not had a measurable impact. Therefore, a fundamental reconsideration of the overall approach is reasonable and warranted. The ability to provide a modest pressure boost (2 to 6 mmHg) to existing blood flow at the total cavopulmonary connection can effectively restore more stable biventricular status. This would impact not only treatment of late Fontan failure, but also facilitate early surgical repair. A realistic means to provide such a pressure boost has never been apparent. Recent advances are beginning to unravel the unique challenges that must be addressed to realize this goal, with promise to open single-ventricle palliation to new therapeutic vistas.

Physiologic control of rotary blood pumps: An in vitro study

Rotary blood pumps (RBPs) are currently being used as a bridge to transplantation as well as for myocardial recovery and destination therapy for patients with heart failure. Physiologic control systems for RBPs that can automatically and autonomously adjust the pump flow to match the physiologic requirement of the patient are needed to reduce human intervention and error, while improving the quality of life. Physiologic control systems for RBPs should ensure adequate perfusion while avoiding inflow occlusion via left ventricular (LV) suction for varying clinical and physical activity conditions. For RBPs used as left ventricular assist devices (LVADs), we hypothesize that maintaining a constant average pressure difference between the pulmonary vein and the aorta (ΔPa) would give rise to a physiologically adequate perfusion while avoiding LV suction. Using a mock circulatory system, we tested the performance of the control strategy of maintaining a constant average ΔPa and compared it with the results obtained when a constant average pump pressure head (ΔP) and constant rpm are maintained. The comparison was made for normal, failing, and asystolic left heart during rest and at light exercise. The ΔPa was maintained at 95 ± l mm Hg for all the scenarios. The results indicate that the ΔPa control strategy maintained or restored the total flow rate to that of the physiologically normal heart during rest (3.8 L/m) and light exercise (5.4 L/m) conditions. The ΔPa approach adapted to changing exercise and clinical conditions better than the constant rpm and constant ΔP control strategies. The ΔPa control strategy requires the implantation of two pressure sensors, which may not be clinically feasible. Sensorless RBP control using the ΔPa algorithm, which can eliminate the failure prone pressure sensors, is being currently investigated.

Rotary pumps and diminished pulsatility: do we need a pulse?

Ventricular assist devices (VADs) have been successfully used as a bridge to heart transplant and destination therapy (DT) for congestive heart failure (HF) patients. Recently, continuous flow VAD (CVAD) has emerged as an attractive clinical option for long-term mechanical support of HF patients, with bridge-to-transplant outcomes comparable with pulsatile flow VAD (PVAD). Continuous flow VADs are smaller, more reliable, and less complex than the first-generation PVAD. Despite the widespread clinical use, CVAD support has been associated with gastrointestinal bleeding, hemorrhagic strokes, and aortic valve insufficiency. Speculation that diminished arterial pressure pulsatility associated with continuous flow devices may be contributing to these complications has sparked much debate over CVAD support. Studies comparing pulsatile flow and continuous flow (CF) support have presented conflicting findings, and the relevance to CVAD as DT is uncertain due to variations in device operation, support duration, and the criteria used to quantify pulsatility. Currently, there is interest in developing control algorithms for CVAD to increase the delivered pulsatility as a strategy to mitigate adverse event risks associated with CVAD therapy. There may also be the added benefit of specific control strategies for managing CVAD therapy, potentially improving the rate of myocardial recovery and successful weaning of mechanical circulatory support.