Novel Image-Guided Percutaneous Lung Tissue Excision Device With Integrated Sealing of Blood Vessels and Airways: An In Vivo Preclinical Study.

OBJECTIVE: This study evaluated the efficacy of the Minimally Invasive Targeted Resection (MiTR) device, a novel electrosurgical instrument that allows for targeted excision of a lung abnormality while using bipolar radiofrequency (RF) energy to seal blood vessels and airways. METHODS: The MiTR system was evaluated in 7 acute and 2 chronic porcine (7-day) models to evaluate the efficacy of tissue excision with bipolar RF sealing of blood vessels and airways and application of an autologous blood patch into the excised tissue cavity. Air leak was recorded for all evaluations. The study was approved by the institutional ethical board. RESULTS: Nineteen lung tissue samples, measuring 2.5 cm long × 1.2 cm diameter, were excised. In 8 of 9 animals (89%), hemostasis and pneumostasis were observed visually at the completion of the procedure. In 2 of 2 chronic animals (100%), hemostasis and pneumostasis persisted for the 7-day observation period. Histologic examination of the excised samples showed preservation of the core parenchymal architecture without evident tissue damage of the samples that would impair pathologic analysis. CONCLUSIONS: Percutaneous resection of targeted lung tissue with the MiTR system demonstrated hemostasis and pneumostasis while obtaining a histologically intact sample. After regulatory approval, the use of this device could offer more tissue for analysis than a transthoracic needle biopsy or bronchoscopy and a far less invasive alternative to video-assisted thoracic surgery or thoracotomy. This may also expand patient and physician options for the early diagnosis and treatment of lung cancer.

Feasibility of long-term continuous flow total heart replacement in calves.

INTRODUCTION: Implementation of continuous flow (CF) technology in modern ventricular assist devices (VAD) has afforded a wealth of engineering and design advantages in the development of a total artificial heart (TAH). However, clinical application of CF has created a unique physiologic state, the consequences of which remain largely unknown. We sought to evaluate clinical and biochemical markers of end-organ function in calves supported with biventricular CF VADs for more than 30 days. METHODS: Eight calves survived longer than 30 days following biventriculectomy and implantation of dual CF VADs. Four types of CF pumps were utilized for the study. Serial hematologic and biochemical profiles were drawn as markers for end-organ function, and hemodynamic data-including pump flows and intravascular pressures-were continuously monitored. RESULTS: The eight calves survived an average of 58.8 days (range 30-92 days). Two of the calves were electively terminated at the conclusion of the study period, while the remaining animals were euthanized as a result of respiratory distress (n = 2) or impaired pump flows (n = 4). In each case, serial biochemical and hematologic values were suggestive of preserved end-organ function. Six animals successfully participated in treadmill exercise evaluations. No evidence of end-organ damage was encountered upon necropsy or histologic tissue analysis. CONCLUSION: Biventricular CF VAD implantation permits a viable bovine CFTAH model capable of demonstrating long-term survival. After 30 days of completely nonpulsatile flow, cumulative hemodynamic, clinical, biochemical, and histological analyses were consistent with preserved end-organ function, suggesting previously unreported long-term feasibility of a CFTAH design.

Applicability of Narrow Groove Theory in Designing Washout Features for Rotary Blood Pumps.

High and low shear regions in rotary blood pumps require sufficient washout flow to minimize blood residence time, thereby preventing hemolysis or regions of stasis that can lead to pump thrombosis. Spiral groove bearings (SGBs) both enhance pump washout and reduce erythrocyte exposure to high shear. Narrow groove theory (NGT) has been used as an analytical tool to estimate the flow performance of a flat SGB during the design stage. However, NGT cannot accurately predict the performance of a conical SGB. In this study, we formulated an analytical model from the established NGT by adding an inertia correction term to incorporate variations in centrifugal force, which improved washout prediction in a conical SGB. The modified NGT model was then validated by comparison with experimental results. The results show that the modified NFT analytical model can reasonably predict washout rate when the spiral groove geometry favors creep flow conditions. The conical half angle of the SGB had the most significant impact on washout, with a decrease in half angle leading to large increases in wash-out flow. Small half angles also maintained viscous pumping at larger Reynolds numbers. In summary, the modified NGT can be a useful tool for designing conical SGBs for rotary blood pump washout within the creep flow regime.

Continuous-Flow Left Ventricular Assist Device Explantation After More Than 5 Years of Circulatory Support and Ventricular Reconditioning.

Continuous-flow left ventricular assist devices have proved to be effective, durable, life-saving tools in patients with end-stage heart failure. However, because of the risks associated with mechanical circulatory support (including stroke, infection, gastrointestinal bleeding, and device malfunction), the optimal goal of device therapy is myocardial recovery and device removal. Ventricular reconditioning and pump explantation after continuous-flow support have been reported; however, little is known about variables that govern the pace and degree of myocardial response in patients who experience such recovery. We describe our long-term pump-weaning strategy for a 25-year-old man who had a continuous-flow device implanted and then needed more than 5 years of support from it before developing cardiac reserve sufficient to enable pump explantation. To our knowledge, this is the longest period of uninterrupted continuous-flow device support to end in successful pump deactivation and a return to medical therapy. This case highlights the importance of actively and persistently pursuing a device-weaning strategy in all patients who need left ventricular assist device therapy.

Pericardial Access Through the Right Atrium in a Porcine Model.

As procedures such as epicardial ventricular ablation and left atrial appendage occlusion become more commonplace, the need grows for safer techniques to access the physiologic pericardial space. Because this space contains minimal fluid for lubrication, prevailing methods of pericardial access pose considerable periprocedural risk to cardiac structures. Therefore, we devised a novel method of pericardial access in which carbon dioxide (CO2) is insufflated through a right atrial puncture under fluoroscopic guidance, enabling clear visualization of the cardiac silhouette separating from the chest wall. We performed the procedure in 8 Landrace pigs, after which transthoracic percutaneous pericardial access was obtained by conventional means. All of the animals remained hemodynamically stable during the procedure, and none showed evidence of epicardial or coronary injury. The protective layer of CO2 in the pericardial space anterior to the heart facilitated percutaneous access in our porcine model, and the absence of complications supports the potential safety of this method.

Investigation of the inherent left-right flow balancing of rotary total artificial hearts by means of a resistance box.

With the incidence of end-stage heart failure steadily increasing, the need for a practical total artificial heart (TAH) has never been greater. Continuous flow TAHs (CFTAH) are being developed using rotary blood pumps (RBPs), leveraging their small size, mechanical simplicity, and excellent durability. To completely replace the heart with currently available RBPs, two are required; one for providing pulmonary flow and one for providing systemic flow. To prevent hazardous states, it is essential to maintain balance between the pulmonary and systemic circulation at a wide variety of physiologic states. In this study, we investigated factors determining a CFTAH's inherent ability to balance systemic and pulmonary flow passively, without active management of pump rotational speed. Four different RBPs (ReliantHeart HA5, Thoratec HMII, HeartWare HVAD, and Ventracor VentrAssist) were used in various combinations to construct CFTAHs. Each CFTAH's ability to autonomously maintain pressures and flows within defined ranges was evaluated in a hybrid mock loop as systemic and pulmonary vascular resistance (PVR) were changed. The resistance box, a method to quantify the range of vascular resistances that can be safely supported by a CFTAH, was used to compare different CFTAH configurations in an efficient and predictive way. To reduce the need for future in vitro tests and to aid in their analysis, a novel analytical evaluation to predict the resistance box of various CFTAH configurations was also performed. None of the investigated CFTAH configurations fully satisfied the predefined benchmarks for inherent flow balancing, with the VentrAssist (left) and HeartAssist 5 (right) offering the best combination. The extent to which each CFTAH was able to autonomously maintain balance was determined by the pressure sensitivity of each RPB: the sensitivity of outflow to changes in the pressure head. The analytical model showed that by matching left and right pressure sensitivity the inherent balancing performance can be improved. These findings may ultimately lead to a reduced need for manual speed changes or active control systems.

Simple Felt-Plug Closure Technique for Minimally Invasive Removal of a Centrifugal-Flow Left Ventricular Assist Device.

As the indications for implanting left ventricular assist devices have expanded, some patients are qualifying for device removal after myocardial recovery. Whereas explantation has been described for previous generations of devices, no standard procedures have been developed. Removal of centrifugal-flow devices has created the need for a plug to seal the apical ventriculotomy after pump removal. However, no commercially available products are available in the United States. We used a novel technique to fashion a plug from Teflon felt and a Dacron graft to enable minimally invasive explantation of a current-generation centrifugal-flow device in a 33-year-old woman.

Low Incidence of Pump-Related Infections in Jarvik 2000 Ventricular Assist Device Recipients with a Subcostal Driveline Exit Site.

Driveline infection has been a persistent problem with mechanical cardiac assist devices. The reported incidence of infection has been low in patients who receive a Jarvik 2000 continuous-flow left ventricular assist device when a skull-pedestal driveline exit site is used. We evaluated whether this is also true when a subcostal driveline exit site is used. We reviewed baseline demographic variables, postimplantation vital signs, laboratory values, and culture results in patients who underwent Jarvik 2000 implantation at our center from April 2000 through October 2009, including follow-up through June 2014. All patients had a subcostal driveline exit site. We defined device-related infection as a positive blood or wound culture associated with a medical or surgical device intervention. Event and time-to-event rates were calculated. Eighty-one patients received 89 Jarvik 2000 devices, all as bridges to transplantation. The median support duration was 69 days (interquartile range, 27-153 d; range, 2-2,249 d). Five superficial driveline infections and one incision-site infection occurred (0.002 events per patient-year of support). The median time from pump implantation to onset of driveline infection was 30 days; the incision-related infection occurred at 44 days. The Jarvik 2000 has a low incidence of infection when implanted with use of a subcostal driveline exit site. The incidence of pump infections is particularly low. Using a subcostal driveline exit site may be as effective in preventing infections as using a skull-pedestal driveline exit site. We detail our findings in this report.

Experience with the HeartMate II Left Ventricular Assist Device in Patients Older than 60 Years.

BACKGROUND: Advanced age is a relative contraindication for heart transplantation, but no age cutoff has been defined for patients receiving mechanical circulatory support. METHODS: Between November 1, 2003 and November 1, 2012, we implanted the HeartMate II (HMII) left ventricular assist device (LVAD) in 319 patients. One hundred seven patients (89 men, 18 women) were over 60 years old (mean, 66 ± 4 years, range, 61-78 years) and received the HMII as a bridge to transplantation (n = 45) or as destination therapy (n = 62). We evaluated their experience by performing a retrospective analysis. RESULTS: Seventy-two patients had ischemic cardiomyopathy, and 34 had idiopathic cardiomyopathy. Three patients (2.8%) already had a HeartMate XVE LVAD, 54 (50.5%) were receiving intra-aortic balloon pump support, 52 (48.6%) had undergone a previous cardiac procedure, and 9 (8.4%) had received renal replacement therapy (RRT) (continuous venovenous hemofiltration, hemodialysis, or both) before HMII implantation. The median duration of HMII support was 313 days (range, 1-3339 days). After device implantation, 36 patients (33.6%) had gastrointestinal bleeding, 24 (23%) required RRT, 18 (17.5%) had ventricular arrhythmias, and 24 (22.4%) had LVAD-related infections, and 9 (8.4%) had right ventricular failure requiring mechanical support, and 28 (26.2%) had neurologic complications. The actual survival rate was 69% at 6 months, 63% at 1 year, and 54% at 2 years. Eighty-one patients died, 9 are still receiving HMII support, and 17 are alive after heart transplantation. CONCLUSIONS: Older patients can benefit from LVAD therapy, and advanced age should not preclude LVAD implantation.

Evaluation of the CorInnova Heart Assist Device in an Acute Heart Failure Model.

While the number of patients supported with temporary cardiac assist is growing, the existing devices are limited by a multitude of complications, mostly related to contact with the blood. The CorInnova epicardial compressive heart assist device was tested in six sheep using an acute heart failure model. High esmolol dose, targeting a 50% reduction in CO from healthy baseline, resulted in a failure state with mean CO 1.9 L/min. Heart assist with the device during failure state resulted in an average absolute increase in CO of 1.0 L/min, along with a decline in ventricular work to 67.5% of the total LV SW. Combined with repeated success of minimally invasive device implant, the resulting increases in cardiac hemodynamics achieved while still unloading the heart demonstrate the potential of the CorInnova device for temporary heart assist.

Long-Term Continuous-Flow Left Ventricular Assist Device Support After Left Ventricular Outflow Tract Closure.

Aortic valve insufficiency can be addressed during continuous-flow left ventricular assist device (CF-LVAD) implantation by performing aortic valve repair or replacement, or patch closure of the left ventricular outflow tract (LVOT). However, few studies have examined the safety of long-term CF-LVAD support after LVOT closure. From November 2003 through March 2016, 16 patients with advanced chronic heart failure underwent CF-LVAD implantation and concomitant LVOT closure for severe aortic insufficiency. We compared their long-term outcomes with those of 510 CF-LVAD recipients without concomitant LVOT closure. Total support time was 26.1 patient-years in the LVOT-closure group and 938.6 patient-years in the CF-LVAD-only group. Survival at 30 days, 6 months, 1 year, and 2 years was similar for CF-LVAD-only patients (90.4%, 80.6%, 74.3%, 67.5%) and LVOT-closure patients (81.3%, 81.3%, 75.0%, 68.8%; p = 0.59). There were no deaths related to LVOT closure. The event rate per patient-year for neurologic dysfunction (ND) was 0.23 in the LVOT-closure group (6 ND events) and 0.20 in the CF-LVAD-only group (136 ND events; p = 0.97). We conclude that for select patients with aortic insufficiency who are undergoing CF-LVAD implantation, LVOT closure produces acceptable outcomes and, therefore, is a viable option.

Design Method Using Statistical Models for Miniature Left Ventricular Assist Device Hydraulics.

Left ventricular assist devices (LVADs) are increasingly used to treat heart failure patients. These devices' impeller blades and diffuser vanes must be designed for hydraulic performance and hemocompatibility. The traditional design method, applying mean-line theory, is not applicable to the design of small-scale pumps such as miniature LVADs. Furthermore, iterative experimental testing to determine how each geometric variable affects hydraulic performance is time and labor intensive. In this study, we tested a design method wherein empirical hydraulic results are used to establish a statistical model to predict pump hydraulic performance. This method was used to design an intra-atrial blood pump. Five geometric variables were chosen, and each was assigned two values to define the variable space. The experimental results were then analyzed with both correlation analysis and linear regression modeling. To validate the linear regression models, 2 test pumps were designed: mean value of each geometric variable within the boundaries, and random value of each geometric variable within the boundaries. The statistical model accurately predicted the hydraulic performance of both pump designs within the boundary space. This method could be expanded to include more geometric variables and broader boundary conditions, thus accelerating the design process for miniature LVADs.

Hemodynamic Evaluation of an Intra-Atrial Blood Pump on a Pulsatile Mock Circulatory Loop.

An intra-atrial pump (IAP) was proposed that would be affixed to the atrial septum to support the compromised left ventricle (LV) without harming the ventricular tissue in patients with early-stage heart failure. The IAP is designed to operate in parallel with the LV, drawing blood from the left atrium and unloading the LV. In previous hydraulic studies, different blade geometries were tested for the IAP; however, it is important to know how the blade geometry affects the IAP's hemodynamic performance in the human cardiovascular system. In this study, a mock circulatory loop (MCL) with physiological response was used to evaluate the hemodynamic effects of IAP blade geometry and connection configuration in the human cardiovascular system. In a $2 \times 2$ study, two different blade geometries (with steep vs flat pressure/flow curves) were tested in two different connection configurations: the proposed configuration (left atrium to aorta) and the conventional configuration for LVADs (LV to aorta). We found that atrial cannulation is feasible and creates a beneficial hemodynamic environment, although it is inferior to the one created by ventricular cannulation. The steepgradient pump performed better than the flat-gradient pump in atrial insertion.

In Vivo Feasibility Study of an Intra-Atrial Blood Pump for Partial Support of the Left Ventricle.

We are designing an intra-atrial pump (IAP) that will be affixed to the atrial septum and support the compromised left ventricle (LV) in patients with early-stage heart failure without harming the ventricular tissue. It will operate in parallel with the LV, drawing blood from the left atrium and unloading the LV. In previous hydraulic and hemodynamic studies, different blade geometries were tested for the IAP, and the hemodynamic results obtained using a mock circulatory loop showed that the IAP can successfully reduce end-diastolic volume and increase the total systemic flow rate. In the current study, we used a bovine model to validate the in vitro hemodynamic results and better understand how the IAP interacts with the cardiovascular system in vivo. Because this was the first study assessing the complete device in a living system, it was also necessary to determine the best manufacturing techniques and ideal sensor placements. In the bovine model, we were able to successfully implant the IAP across the atrial septum with the outflow graft connected to a peripheral artery. The implanted IAP was capable of providing partial support (1-3 L/min) in vivo. These results indicate that atrial cannulation is feasible and creates a beneficial hemodynamic environment.

Long-Term Continuous-Flow Biventricular Support in a 63-Year-Old Woman.

We describe the successful use of long-term biventricular continuous-flow mechanical circulatory support as a bridge to transplantation in a small-framed 63-year-old woman with long-standing nonischemic cardiomyopathy. After placement of a left-sided HeartWare HVAD, persistent right-sided heart failure necessitated implantation of a second HeartWare device for long-term right ventricular support. After 262 days, the patient underwent successful orthotopic heart transplantation and was discharged from the hospital. This report indicates the feasibility of biventricular device support in older patients of relatively small stature, and our results may encourage others to consider this therapy in similar patient populations.

Pulsatile operation of a continuous-flow right ventricular assist device (RVAD) to improve vascular pulsatility.

Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction. In addition, the performance of the speed modulation strategy has been assessed under different cardiovascular states, including variation in ventricular contractility and pulmonary arterial compliance. Our results indicated that the proposed pulse profile with optimised parameters (Apulse = 10000 rpm and ωmin = 3000 rpm) was able to generate pulmonary arterial pulse pressure within the physiological range (9-15 mmHg) while avoiding undesirable pump backflow under both co- and counter-pulsation modes. As compared to co-pulsation, stroke work was reduced by over 44% under counter-pulsation, suggesting that mechanical workload of the right ventricle can be efficiently mitigated through counter-pulsing the pump speed. Furthermore, our results showed that improved ventricular contractility could potentially lead to higher risk of ventricular suction and pump backflow, while stiffening of the pulmonary artery resulted in increased pulse pressure. In conclusion, the proposed speed modulation strategy produces pulsatile hemodynamics, which is more physiologic than continuous blood flow. The findings also provide valuable insight into the interaction between RVAD speed modulation and the pulmonary circulation under various cardiovascular states.

Preliminary design of the internal geometry in a minimally invasive left ventricular assist device under pulsatile-flow conditions.

PURPOSE: A minimally invasive, partial-assist, intra-atrial blood pump has been proposed, which would unload the left ventricle with a flow path from the left atrium to the arterial system. Flow modulation is a common strategy for ensuring washout in the pump, but it can increase power consumption because it is typically achieved through motor-speed variation. However, if a pump's performance curve had the proper gradient, flow modulation could be realized passively. To achieve this goal, we propose a pump performance operating curve as an alternative to the more standard operating point. METHODS AND RESULTS: Mean-line theory was employed to generate an initial set of geometries that were then tested on a hydraulic test rig at ~20,000 r/min. Experimental results show that the intra-atrial blood pump performed below the operating region; however, it was determined that smaller hub diameter and longer chord length bring the performance of the intra-atrial blood pump device closer to the operating curve. CONCLUSION: We found that it is possible to shape the pump performance curve for specifically targeted gradients over the operating region through geometric variations inside the pump.

Bridging to a Long-Term Ventricular Assist Device With Short-Term Mechanical Circulatory Support.

Implanting short-term mechanical circulatory support (MCS) devices as a bridge-to-decision is increasingly popular. However, outcomes have not been well studied in patients who receive short-term MCS before receiving long-term left ventricular assist device (LVAD) support. We analyzed outcomes in our single-center experience with long-term continuous-flow (CF)-LVAD recipients with pre-implantation short-term MCS. From November 2003 through March 2016, 526 patients (mean age, 54.7 ± 13.5 years) with chronic heart failure (mean ejection fraction, 21.7 ± 3.6%) underwent implantation of either the HeartMate II (n = 403) or the HeartWare device (n = 123). Before implantation, 269 patients received short-term MCS with the TandemHeart, the Impella 2.5/5.0, an intra-aortic balloon pump (IABP), venoarterial extracorporeal membrane oxygenation (VA-ECMO), or the CentriMag. The short-term MCS patients were compared with the CF-LVAD-only patients regarding preoperative demographics, incidence of postoperative complications, and long-term survival. The 269 patients received the following short-term MCS devices: 57 TandemHeart, 27 Impella, 172 IABP, 12 VA-ECMO, and 1 CentriMag. Survival at 30 days, 6 months, 1 year, and 2 years was 94.2, 87.2, 79.4, and 72.4%, respectively, for CF-LVAD-only patients versus 91.0, 78.1, 73.4, and 65.6%, respectively, for short-term MCS + CF-LVAD patients (P = 0.17). Within the short-term MCS group, survival at 24 months was poorest for patients supported with VA-ECMO or the TandemHeart (P = 0.03 for both), and survival across all four time points was poorest for patients supported with VA-ECMO (P = 0.02). Short-term MCS was not an independent predictor of mortality in multivariate Cox regression models (hazard ratio = 1.12, 95% confidence interval = 0.84-1.49, P = 0.43). In conclusion, we found that using short-term MCS therapy-except for VA-ECMO-as a bridge to long-term CF-LVAD support was not associated with poorer survival.

Continuous-Flow Left Ventricular Assist Device Implantation in Patients With a Small Left Ventricle.

BACKGROUND: Having a preoperative small left ventricle (LV) has been associated with higher complication and mortality rates after left ventricular assist device (LVAD) implantation; however, the outcomes after continuous-flow LVAD implantation have not been well studied. This is the first large-scale analysis of long-term survival after continuous-flow LVAD implantation in patients with a preoperative small LV. METHODS: Our cohort comprised 511 patients who underwent primary implantation of a HeartMate II (n = 393 [Thoratec, Pleasanton, CA]) or HeartWare HVAD (n = 118 [HeartWare International, Framingham, MA]) at our institution between November 2003 and March 2016. Preoperative small LV was defined as having an LV end-diastolic diameter of 5.5 cm or less. HeartMate II and HVAD recipients with a small LV were compared with patients not having a small LV in terms of perioperative characteristics, complications, and long-term survival. RESULTS: The HeartMate II was implanted in 393 patients (non-small LV, n = 352; small LV, n = 41), and the HVAD was implanted in 118 patients (non-small LV, n = 94; small LV, n = 24). For the HeartMate II recipients, the 24-month survival rate was 66.8% for the non-small LV patients and 56.1% for the small LV patients (p = 0.17); non-small LV patients had significantly better overall survival (p = 0.02). For the HVAD recipients, the 24-month survival rate was 71.3% for the non-small LV patients and 70.8% for the small LV patients (p = 0.96); these groups showed no significant difference in overall survival (p = 0.89). CONCLUSIONS: Although the indications for implantation are different for these two devices, our study suggests that the survival advantage associated with HVAD implantation should be considered when selecting a device for small LV patients.