Surgical Repair for Primary Tricuspid Valve Disease: Individualized Surgical Planning With 3-Dimensional Printing.

Primary tricuspid valve (TV) disease is rare and associated with high operative mortality. Optimal surgical planning requires a precise understanding of the pathological features; however, detailed imaging of the TV can be challenging. We present 4 cases of primary TV disease where 3-dimensional printing was pivotal to operative planning and success. (Level of Difficulty: Advanced.).

Development of a novel in vitro cadaveric model for analysis of biomechanics and surgical treatment of Bertolotti syndrome.

BACKGROUND CONTEXT: Bertolotti syndrome (BS) is caused by pseudoarticulation between an aberrant L5 transverse process and the sacral ala, termed a lumbosacral transitional vertebra (LSTV). BS is thought to cause low back pain and is treated with resection or fusion, both of which have shown success. Acquiring cadavers with BS is challenging. Thus, we combined 3D printing, based on BS patient CT scans, with normal cadaveric spines to create a BS model. We then performed biomechanical testing to determine altered kinematics from LSTV with surgical interventions. Force sensing within the pseudojoint modeled nociception for different trajectories of motion and surgical conditions. PURPOSE: This study examines alterations in spinal biomechanics with LSTVs and with various surgical treatments for BS in order to learn more about pain and degeneration in this condition, in order to help optimize surgical decision-making. In addition, this study evaluates BS histology in order to better understand the pathology and to help define pain generators-if, indeed, they actually exist. STUDY DESIGN/SETTING: Model Development: A retrospective patient review of 25 patients was performed to determine the imaging criteria that defines the classical BS patient. Surgical tissue was extracted from four BS patients for 3D-printing material selection. Biomechanical Analysis. This was a prospective cadaveric biomechanical study of seven spines evaluating spinal motions, and loads, over various surgical conditions (intact, LSTV, and LSTV with various fusions). Additionally, forces at the LSTV joint were measured for the LSTV and LSTV with fusion condition. Histological Analysis: Histologic analysis was performed prospectively on the four surgical specimens from patients undergoing pseudoarthrectomy for BS at our institution to learn more about potential pain generators. PATIENT SAMPLE: The cadaveric portion of the study involved seven cadaveric spines. Four patients were prospectively recruited to have their surgical specimens assessed histologically and biomechanically for this study. Patients under the age of 18 were excluded. OUTCOME MEASURES: Physiological measures recorded in this study were broken down into histologic analysis, tissue biomechanical analysis, and joint biomechanical analysis. Histologic analysis included pathologist interpretation of Hematoxylin and Eosin staining, as well as S-100 staining. Tissue biomechanical analysis included stiffness measurements. Joint biomechanical analysis included range of motion, resultant torques, relative axis angles, and LSTV joint forces. METHODS: This study received funding from the American Academy of Neurology Medical Student Research Scholarship. Three authors hold intellectual property rights in the simVITRO robotic testing system. No other authors had relevant conflicts of interest for this study. CT images were segmented for a representative BS patient and cadaver spines. Customized cutting and drilling guides for LSTV attachment were created for individual cadavers. 3D-printed bone and cartilage structural properties were based on surgical specimen stiffness, and specimens underwent histologic analysis via Hematoxylin and Eosin, as well as S-100 staining. Joint biomechanical testing was performed on the robotic testing system for seven specimens. Force sensors detected forces in the LSTV joint. Kruskal-Wallis tests and Dunnett's tests were used for statistical analysis with significance bounded to p<.05. RESULTS: LSTV significantly reduces motion at the L5-S1 level, particularly in lateral bending and axial rotation. Meanwhile, the LSTV increases adjacent segment motion significantly at the L2-L3 level, whereas other levels have nonsignificant trends toward increased motion with LSTV alone. Fusion involving L4-S1 (L4-L5 and L5-S1) to treat adjacent level degeneration associated with an LSTV is associated with a significant increase in adjacent segment motion at all levels other than L5-S1 compared to LSTV alone. Fusion of L5-S1 alone with LSTV significantly increases L3-L4 adjacent segment motion compared to LSTV alone. Last, ipsilateral lateral bending with or without ipsilateral axial rotation produces the greatest force on the LSTV, and these forces are significantly reduced with L5-S1 fusion. CONCLUSIONS: BS significantly decreases L5-S1 mobility, and increases some adjacent segment motion, potentially causing patient activity restriction and discomfort. Ipsilateral lateral bending with or without ipsilateral axial rotation may cause the greatest discomfort overall in these patients, and fusion of the L5-S1 or L4-S1 levels may reduce pain associated with these motions. However, due to increased adjacent segment motion with fusions compared to LSTV alone, resection of the joint may be the better treatment option if the superior levels are not unstable preoperatively. CLINICAL SIGNIFICANCE: This study's results indicate that patients with BS have significantly altered spinal biomechanics and may develop pain due to increased loading forces at the LSTV joint with ipsilateral lateral bending and axial rotation. In addition, increased motion at superior levels when an LSTV is present may lead to degeneration over time. Based upon results of LSTV joint force testing, these patients' pain may be effectively treated surgically with LSTV resection or fusion involving the LSTV level if conservative management fails. Further studies are being pursued to evaluate the relationship between in vivo motion of BS patients, spinal and LSTV positioning, and pain generation to gain a better understanding of the exact source of pain in these patients. The methodologies utilized in this study can be extrapolated to recreate other spinal conditions that are poorly understood, and for which few native cadaveric specimens exist.

Motion-activated prevention of clogging and maintenance of patency of indwelling chest tubes.

OBJECTIVES: We designed a device that applies motion-activated energy (vibration) to prevent chest-tube clogging and maintain tube patency. We evaluated the efficacy of this device in vitro and in vivo. METHODS: The motion-activated system (MAS) device assembly comprises a direct current motor with an eccentric mass (3.2 g, centroid radius of 4.53 mm) affixed to its motor shaft. The device was tested in vitro using a model of an obstructed chest tube, with clots of bovine blood and human thrombin. The in vivo study (in nine healthy pigs, 46.0 ± 3.3 kg) involved a bilateral minithoracotomy and placement of 32-Fr chest tubes (with and without the device). Whole autologous blood (120 ml) was injected every 15 min into the right and left chest each over 120 min total. RESULTS: Chest-tube drainage over these 2 h using the MAS was significantly higher than that without the device (369 ± 113 ml vs 209 ± 115 ml; P = 0.027). CONCLUSIONS: Our results suggest that the motion-activation of the chest tubes may be an effective tool to maintain chest tubes patent. Further optimization of this technology is required to obtain more consistent prevention of clot deposition within or outside the chest tubes.

A novel method for pulmonary research: assessment of bioenergetic function at the air-liquid interface.

Air-liquid interface cell culture is an organotypic model for study of differentiated functional airway epithelium in vitro. Dysregulation of cellular energy metabolism and mitochondrial function have been suggested to contribute to airway diseases. However, there is currently no established method to determine oxygen consumption and glycolysis in airway epithelium in air-liquid interface. In order to study metabolism in differentiated airway epithelial cells, we engineered an insert for the Seahorse XF24 Analyzer that enabled the measure of respiration by oxygen consumption rate (OCR) and glycolysis by extracellular acidification rate (ECAR). Oxidative metabolism and glycolysis in airway epithelial cells cultured on the inserts were successfully measured. The inserts did not affect the measures of OCR or ECAR. Cells under media with apical and basolateral feeding had less oxidative metabolism as compared to cells on the inserts at air-interface with basolateral feeding. The design of inserts that can be used in the measure of bioenergetics in small numbers of cells in an organotypic state may be useful for evaluation of new drugs and metabolic mechanisms that underlie airway diseases.

Novel application of rapid prototyping for simulation of bronchoscopic anatomy.

OBJECTIVE: The authors used rapid prototyping (RP) technology to create anatomically congruent models of tracheo-bronchial tree for teaching relevant bronchoscopic anatomy. DESIGN: Pilot study. SETTING: A single level tertiary academic medical center. INTERVENTIONS: Two 3 dimensional (3D) models of tracheo-bronchial tree (one showing normal anatomy and another with an early take off of right apical bronchus) were recreated from Computed Tomographic images using RP technology. These images were then attached to mannequins and examined with a flexible fiberoptic bronchoscope (FFB). These images were then compared with the actual FFB images obtained during lung isolation. MEASUREMENTS AND MAIN RESULTS: The images obtained through the 3D models were found to be congruent to actual patient anatomy. CONCLUSIONS: RP can be successfully used to create anatomically accurate models from imaging studies. There is potential for RP to become a valuable educational tool in the future.

Three-dimensional print of a liver for preoperative planning in living donor liver transplantation.

The growing demand for liver transplantation and the concomitant scarcity of cadaveric livers have increased the need for living donor liver transplantation (LDLT). Ensuring the safety of donors and recipients is critical. The preoperative identification of the vascular and biliary tract anatomy with 3-dimensional (3D) printing may allow better preoperative surgical planning, avert unnecessary surgery in patients with potentially unsuitable anatomy, and thereby decrease the complications of liver transplant surgery. We developed a protocol and successfully 3D-printed synthetic livers (along with their complex networks of vascular and biliary structures) replicating the native livers of 6 patients: 3 living donors and 3 respective recipients who underwent LDLT. To our knowledge, these are the first complete 3D-printed livers. Using standardized preoperative, intraoperative, and postoperative assessments, we demonstrated identical anatomical and geometrical landmarks in the 3D-printed models and native livers.

Simulation Based Design and Evaluation of a Transcatheter Mitral Heart Valve Frame.

In certain populations, open heart surgery to replace a diseased mitral valve is not an option, leaving percutaneous delivery a viable alternative. However, a surgical transcatheter based delivery of a metallic support frame incorporating a tissue derived valve puts considerable constraints on device specifications. Expansion to a large diameter from the catheter diameter without mechanical fracture involves advanced device design and appropriate material processing and selection. In this study, a new frame concept is presented with a desirable feature that incorporates wings that protrude during expansion to establish adequate fixation. Expansion characteristics of the design in relation to annulus fixation were quantified through finite element analysis predictions of the frame wing span and angles. Computational modeling and simulation was used to identify many favorable design features for the transcatheter mitral valve frame and obtain desired expansion diameters (35-45mm), acceptable radial stiffness (2.7N/mm), and ensure limited risk of failure based on predicted plastic deformations.

Cycle testing of the MagScrew total artificial heart external battery pack: update I.

MagScrew total artificial heart (TAH) external battery pack (EBP) cycle bench testing continued over a period of 18 months using two fresh Wilson Greatbatch lithium ion EBPs during continuous charge and discharge cycles under a simulated TAH system current requirement. The same electronic load developed for our initial testing was used to simulate the MagScrew current waveforms typically observed during nominal operation. The current load profiles for this test were modified from the ones previously described and applied to the EBP under test during a voltage-defined discharge cycle. The test ended when EBP#2 reached end of life at 1450 cycles. At that point, EBP#1 remained healthy with a capacity of 175 min until full discharge. Performance of EBP#2 was still within expected ranges. Performance of EBP#1 exceeded expectations. These differences are probably caused by slight manufacturing changes. More tests will provide additional data to define a statistical distribution to better characterize EBP performance. In conclusion, endurance performance of the EBP remained satisfactory.

Performance of extracorporeally adjustable ventricular assist device inflow cannula.

PURPOSE: This study evaluated the feasibility and efficacy of a newly developed adjustable left ventricular assist device inflow cannula in a short-term calf model. DESCRIPTION: In this inflow cannula, the angle between the cannula body and the inflow cannula tip can be altered extracorporeally by manipulating 2 externalized cables connected to the cannula. The cannula tip is adjustable in any plane to a maximum of ±15 degrees. EVALUATION: After initial prototyping in 4 calf cadavers, a Cleveland Heart left ventricular assist device was implanted with the adjustable inflow cannula placed in the left ventricular apex and the outlet to the descending aorta. Under hypovolemic conditions, the angle of the cannula tip could be changed to induce varying degrees of ventricular suction and then eliminate it, as evidenced by recorded pump and native left ventricular flows. Epicardial echocardiography and fluoroscopy in the closed-chest condition documented extracorporeal adjustments of the inflow cannula position. CONCLUSIONS: This extracorporeally adjustable inflow cannula was effective in preventing or controlling left ventricular suction.

A fillable micro-hollow sphere lesion detection phantom using superposition.

The lesion detection performance of SPECT and PET scanners is most commonly evaluated with a phantom containing hollow spheres in a background chamber at a specified radionuclide contrast ratio. However, there are limitations associated with a miniature version of a hollow sphere phantom for small-animal SPECT and PET scanners. One issue is that the 'wall effect' associated with zero activity in the sphere wall and fill port causes significant errors for small diameter spheres. Another issue is that there are practical difficulties in fabricating and in filling very small spheres (<3 mm diameter). The need for lesion detection performance assessment of small-animal scanners has motivated our development of a micro-hollow sphere phantom that utilizes the principle of superposition. The phantom is fabricated by stereolithography and has interchangeable sectors containing hollow spheres with volumes ranging from 1 to 14 microL (diameters ranging from 1.25 to 3.0 mm). A simple 60 degrees internal rotation switches the positions of three such sectors with their corresponding background regions. Raw data from scans of each rotated configuration are combined and reconstructed to yield superposition images. Since the sphere counts and background counts are acquired separately, the wall effect is eliminated. The raw data are subsampled randomly prior to summation and reconstruction to specify the desired sphere-to-background contrast ratio of the superposition image. A set of images with multiple contrast ratios is generated for visual assessment of lesion detection thresholds. To demonstrate the utility of the phantom, data were acquired with a multi-pinhole SPECT/CT scanner. Micro-liter syringes were successful in filling the small hollow spheres, and the accuracy of the dispensed volume was validated through repeated filling and weighing of the spheres. The phantom's internal rotation and the data analysis process were successful in producing the expected superposition images. Visual inspection of the multi-contrast images provided simple determination of lesion detection thresholds for this scanner (4:1 ratio for 1.5 mm spheres and 3:1 ratio for 2.0 mm spheres) at a specified cumulated background concentration (30 kBq-min microL(-1)). In summary, the micro-hollow sphere phantom demonstrated its practical utility for lesion detection evaluation and is well suited for comparing the task-based performance of small-animal SPECT and PET scanners.

Reduced pulsatility induces periarteritis in kidney: role of the local renin-angiotensin system.

OBJECTIVE: The need for pulsatility in the circulation during long-term mechanical support has been a subject of debate. We compared histologic changes in calf renal arteries subjected to various degrees of pulsatile circulation in vivo. We addressed the hypothesis that the local renin-angiotensin system may be implicated in these histologic changes. METHODS AND RESULTS: Sixteen calves were implanted with devices giving differing degrees of pulsatile circulation: 6 had a continuous flow left ventricular assist device (LVAD); 6 had a continuous flow right ventricular assist device (RVAD); and 4 had a pulsatile total artificial heart (TAH). Six other calves were histologic and immunohistochemical controls. In the LVAD group, the pulsatility index was significantly lower (0.28 +/- 0.07 LVAD vs 0.56 +/- 0.08 RVAD, vs 0.53 +/- 0.10 TAH; P < 0.01), and we observed severe periarteritis in all cases in the LVAD group. The number of angiotensin II type 1 receptor-positive cells and angiotensin converting enzyme-positive cells in periarterial areas was significantly higher in the LVAD group (angiotensin II type 1 receptor: 350 +/- 139 LVAD vs 8 +/- 6 RVAD, vs 3 +/- 2 TAH, vs 3 +/- 2 control; P < .001; angiotensin-converting enzyme: 325 +/- 59 LVAD vs 6 +/- 4 RVAD, vs 6 +/- 5 TAH, vs 3 +/- 1 control; P < .001). CONCLUSIONS: The reduced pulsatility produced by a continuous flow LVAD implantation induced severe periarteritis in the kidneys. The local renin-angiotensin system was up-regulated in the inflammatory cells only in the continuous flow LVAD group.

Pressures generated within the chambers of the MagScrew TAH: an in vitro study.

Incompetent inflow valves have been reported with clinical pulsatile left ventricular assist devices that use bioprosthetic valves. Suspected as the cause of premature valve failure within these devices, absolute pressures and instantaneous pressure changes were evaluated in the MagScrew total artificial heart (TAH). The MagScrew TAH is a passively filling pulsatile pump which uses a reciprocating magnetic actuating mechanism under various control modes to propel blood into circulation. Both right and left ejection speeds were modulated and optimized at the onset of hydraulic eject. These various speed profiles were evaluated in vitro at 220 beats per minute (bpm), 100% pump fill, mean aortic pressure of 100 mm Hg and mean pulmonary artery pressure of 20 mm Hg. The pressure inside the left and right pump chambers was measured with Millar Mikro-Tip catheter and captured using Power Lab at a rate of 40 kHz. The pump chamber peak pressure, operating with unmodified eject speeds, measured on average 183 mm Hg for the left and 133 mm Hg for the right. Eject speed profiling for both pumps reduced the peak pressure by 10% and 28% for the left and right pump, respectively. Future studies will assess software controlled optimization of the eject speed profiles under any operating condition and how effective it is in vivo.

Hemodynamic and metabolic changes during exercise in calves with total artificial hearts of different sizes yet similar output.

To evaluate the effects of downsizing of the total artificial heart (TAH), we compared the anaerobic threshold (AT) values in calves with two different types of TAH (Cleveland Clinic-Nimbus TAH and the downsized MagScrew TAH). Exercise studies were performed using a treadmill in 12 calves. During the exercise, parameters to obtain the AT were measured. To evaluate the determinants of the AT, a linear regression analysis was performed between AT and potential variables. AT values from 29 studies revealed no significant differences between the two different TAHs, with no significant differences in hemodynamic or oxygen metabolic parameters. AT values correlated well with pump flow/body weight (Q) multiplied by the hemoglobin level, regardless of the TAH used. In conclusion, downsizing of the original TAH design did not reduce AT without any significant differences in hemodynamic or oxygen metabolic parameters during exercise in calves.

Cycle testing of the MagScrew total artificial heart external battery pack.

MagScrew total artificial heart (TAH) external battery pack (EBP) cycle bench testing was conducted on two Wilson Greatbatch (Clarence, NY, USA) lithium ion EBPs over a period of 22 months during continuous charge and discharge cycles under a simulated TAH system current requirement. A custom electronic load was developed to simulate the MagScrew current waveforms typically observed during nominal operation. These current load profiles were applied to the EBP under test during a voltage-defined discharge cycle. EBP endurance indicated a 240-min discharge cycle on a new battery diminishing linearly to 175 min after 800 cycles. A second linear trend started at this knee with 150 min of discharge time at 850 cycles until 10 min at 1600 cycles. Even at 1300 cycles, the EBP could still provide enough power for 60 min of nominal operation. In conclusion, the endurance performance of this EBP was satisfactory while exhibiting a predictable wear-out trend.

Replacement of the left-side valves of an implanted total artificial heart.

The MagScrew total artificial heart (TAH) is under development. Despite its anticipated durability and reliability, the possibility of a bioprosthetic valve malfunction exists. As a result, the potential for valve replacement surgery, instead of device replacement, would be desirable after a TAH implant. In two of our 90-day animal experiments, we successfully replaced the left-side valves through a left thoracotomy opposite to the right-sided incision site for the initial TAH implant. The results of these cases suggest that the left-side valves could also be replaced through a left thoracotomy approach in humans. To confirm the ability to access the left-side valves in humans, four human cadaver studies were performed with the use of a mock pump designed for human application. This report describes the operative techniques for left-side valve replacement in animals and discusses the advantages of a left thoracotomy in clinical situations, based on results from the human cadaver studies.

MagScrew TAH: an update.

The MagScrew Total Artificial Heart (TAH) system is the result of a close collaboration among the Cleveland Clinic Foundation, Foster Miller Technologies, Wilson Greatbatch Ltd, and Whalen Biomedical Inc. The system components are the thoracic blood pumping unit with attached compliance chamber and refill port, implantable electronic control unit, implantable battery pack, transcutaneous energy transmission system, external battery pack, and a telemetry system for communication with the electronic control unit. System in vitro tests are underway for system characterization and durability demonstration, whereas in vivo tests were conducted to evaluate system performance and biocompatibility under physiologic conditions. The passively filling pump uses a left master alternate left and right ejection control mode and has a Starling law-like response to venous pressure. The in vitro tests documented excellent hydraulic pump performance with high device output of over 9 l/min at left atrial pressures below 12 mm Hg. Atrial balance was well maintained under all test conditions. The in vivo tests demonstrated good biocompatibility without use of anticoagulant therapy. Experimental durations have ranged between 0 and 92 days. Postexplant evaluation of tissue samples did not reveal any sign of thromboembolic events or tissue damage due to device operation.

MagScrew total artificial heart in vivo performance above 200 beats per minute.

PURPOSE: Downsizing pulsatile devices requires an increase of beat rate if flow capacity is to be maintained. We applied this concept to the preclinical MagScrew total artificial heart (TAH). DESCRIPTION: The device fills passively with a stroke volume of 45 ml and beat rates up to 250 beats per minute (bpm). EVALUATION: Stable hemodynamics were observed during a 30-day bovine implant with a flow of 8.7 +/- 1.2 L/min at beat rates of 204 +/- 18 bpm. Device filling was exceptional up to 250 bpm generating flow of greater than 12 L/min. Beat rate adapted to preload in a way similar to a Frank-Starling response. Left and right atrial pressures were balanced. The aortic pulse pressure was 49-70 mm Hg, which translates to a pulsatility index of 0.49-0.77. Organ functions were preserved and blood damage did not occur. CONCLUSIONS: Increasing the beat rate while downsizing the MagScrew TAH was successful with strong flow generation by passive filling. Pulsatility was maintained at high beat rates. This innovative approach may be used to develop small pulsatile pumps.