Cleveland Clinic Continuous-Flow Total Artificial Heart: Progress Report and Technology Update.

Cleveland Clinic's continuous-flow total artificial heart (CFTAH) is being developed at our institution and has demonstrated system reliability and optimal performance. Based on the results from recent chronic in vivo experiments, CFTAH has been revised, especially to improve biocompatibility. The purpose of this article is to report our progress in developing CFTAH. To improve biocompatibility, the right impeller, the pump housing, and the motor were reviewed for design revision. Updated design features were based on computational fluid dynamics analysis and observations from in vitro and in vivo studies. A new version of CFTAH was created, manufactured, and tested. All hemodynamic and pump-related parameters were observed and found to be within the intended ranges, and the new CFTAH yielded acceptable biocompatibility. Cleveland Clinic's continuous-flow total artificial heart has demonstrated reliable performance, and has shown satisfactory progress in its development.

Preservation of pulsatility with universal ventricular assist device: In vitro assessment for biventricular support.

BACKGROUND: The objective of this study was to assess the pulsatility preservation capability of the universal ventricular assist device (UVAD) when used as a biventricular assist device (BVAD). This evaluation was conducted through an in vitro experiment, utilizing a pulsatile biventricular circulatory mock loop. METHODS: Two UVAD pumps were tested in a dual setup (BVAD) in the circulatory model with the simulated conditions of left heart failure (HF), right HF, and moderate/severe biventricular HF (BHF). The total flow, aortic pulse pressure, the pulse augmentation factor (PAF), the energy-equivalent pressure (EEP), and the surplus hemodynamic energy (SHE) were observed at various pump speeds to evaluate the pulsatility. RESULTS: The aortic pulse pressure increased from the baseline (without pump) in all simulated hemodynamic conditions. The PAF ranged from 17%-35% in healthy, left HF, right HF, and mild BHF conditions, with the highest PAF of 90% being observed in the severe BHF condition. The EEP correlated with LVAD flow in all groups (R2 = 0.87-0.97) and increased from the baseline in all cases. The SHE peaked at approximately 5-6 L/min of LVAD support and was likely to decrease at higher LVAD pump flow. The largest decrease in SHE from the baseline, 53%, was observed in the mild BHF conditions with the highest LVAD and RVAD support. CONCLUSIONS: The UVAD successfully demonstrated the ability to preserve pulsatility in vitro, and to optimize the cardiac output, as an isolated circulatory support device option (RVAD or LVAD) and when used for BVAD support.

Artificial Deep Neural Network for Sensorless Pump Flow and Hemodynamics Estimation During Continuous-Flow Mechanical Circulatory Support.

The objective of this study was to compare the estimates of pump flow and systemic vascular resistance (SVR) derived from a mathematical regression model to those from an artificial deep neural network (ADNN). Hemodynamic and pump-related data were generated using both the Cleveland Clinic continuous-flow total artificial heart (CFTAH) and pediatric CFTAH on a mock circulatory loop. An ADNN was trained with generated data, and a mathematical regression model was also generated using the same data. Finally, the absolute error for the actual measured data and each set of estimated data were compared. A strong correlation was observed between the measured flow and the estimated flow using either method (mathematical, R = 0.97, p < 0.01; ADNN, R = 0.99, p < 0.01). The absolute error was smaller in the ADNN estimation (mathematical, 0.3 L/min; ADNN 0.12 L/min; p < 0.01). Furthermore, strong correlation was observed between measured and estimated SVR (mathematical, R = 0.97, p < 0.01; ADNN, R = 0.99, p < 0.01). The absolute error for ADNN estimation was also smaller than that of the mathematical estimation (mathematical, 463 dynes·sec·cm -5 ; ADNN, 123 dynes·sec·cm -5 , p < 0.01). Therefore, in this study, ADNN estimation was more accurate than mathematical regression estimation. http://links.lww.com/ASAIO/A991.

Biventricular circulatory support using single-device and dual-device configurations: Initial pump characterization in simulated heart failure model.

Objective: Severe biventricular heart failure (BHF) can be remedied using a biventricular assist device (BVAD). Two devices are currently in development: a universal ventricular assist device (UVAD), which will be able to assist either the left, right, or both ventricles, and a continuous-flow total artificial heart (CFTAH), which replaces the entire heart. In this study, the in vitro hemodynamic performances of two UVADs are compared to a CFTAH acting as a BVAD. Methods: For this experiment, a biventricular mock circulatory loop utilizes two pneumatic pumps (Abiomed AB5000™, Danvers, MA, USA), in conjunction with a dual-output driver, to create heart failure (HF) conditions (left, LHF; right, RHF; biventricular, BHF). Systolic BHF for four different situations were replicated. In each situation, CFTAH and UVAD devices were installed and operated at two distinct speeds, and cannulations for ventricular and atrial connections were evaluated. Results: Both CFTAH and UVAD setups achieved our recommended hemodynamic criteria. The dual-UVAD arrangement yielded a better atrial balance to alleviate LHF and RHF. For moderate and severe BHF scenarios, CFTAH and dual UVADs both created excellent atrial pressure balance. Conversely, when CFTAH was atrial cannulated for LHF and RHF, the needed atrial pressure balance was not met. Conclusion: Comprehensive in vitro testing of two different BVAD setups exhibited self-regulation and exceptional pump performance for both (single- and dual-device) BHF support scenarios. For treating moderate and severe BHF, UVAD and CFTAH both functioned well with respect to atrial pressure regulation and cardiac output. Though, the dual-UVAD setup yielded a better atrial pressure balance in all BHF testing scenarios.

Mechanical circulatory support devices and treatment strategies for right heart failure.

The importance of right heart failure (RHF) treatment is magnified over the years due to the increased risk of mortality. Additionally, the multifactorial origin and pathophysiological mechanisms of RHF render this clinical condition and the choices for appropriate therapeutic target strategies remain to be complex. The recent change in the United Network for Organ Sharing (UNOS) allocation criteria of heart transplant may have impacted for the number of left ventricular assist devices (LVADs), but LVADs still have been widely used to treat advanced heart failure, and 4.1 to 7.4% of LVAD patients require a right ventricular assist device (RVAD). In addition, patients admitted with primary left ventricular failure often need right ventricular support. Thus, there is unmet need for temporary or long-term support RVAD implantation exists. In RHF treatment with mechanical circulatory support (MCS) devices, the timing of the intervention and prediction of duration of the support play a major role in successful treatment and outcomes. In this review, we attempt to describe the prevalence and pathophysiological mechanisms of RHF origin, and provide an overview of existing treatment options, strategy and device choices for MCS treatment for RHF.

Novel approaches for left atrial pressure relief: Device-based monitoring and management in heart failure.

The importance of the left atrium (LA) has been emphasized in recent years as the features of heart failure (HF), especially with regard to variability in patient and pathology phenotypes, continue to be uncovered. Of note, among the population with HF with preserved ejection fraction (HFpEF), pressure or size of the LA have become a target for advanced monitoring and a therapeutic approach. In the case of diastolic dysfunction or pulmonary hypertension, which are often observed in patients with HFpEF, a conventional approach with clinical symptoms and physical signs of decompensation turned out to have a poor correlation with LA pressure. Therefore, to optimize HF treatment for these populations, several devices that are applied directly to the LA have been developed. First, two LA pressure (LAP) sensors (Heart POD and V-LAP Device) were developed and may enable patient self-management remotely with LAP-guided and physician-directed style. Second, there are device-based approaches that aim to decompress the LA directly. These include: (1) interatrial shunt devices; (2) left ventricular assist devices with LA cannulation; and (3) the left atrial assist device. While these novel device-based therapies are not yet commercially available, there is expected to be a rise in the proposition and adoption of a wider range of choices for monitoring or treating LA using device-based options, based on LA dimensional reduction and optimization of the clinically significant pressure relief. Further development and evaluation are necessary to establish a more favorable management strategy for HF.

Pulsatility hemodynamics during speed modulation of continuous-flow total artificial heart in a chronic in vivo model.

BACKGROUND: The evaluation of pulsatile flow created by the new Cleveland Clinic continuous-flow total artificial heart (CFTAH100), which has a re-designed right impeller and motor, had not been tested in vivo. The purpose of this study was to evaluate the feasibility of pulsatility with the CFTAH100 during the application of pump speed modulation protocols in a chronic animal model. METHODS: A 30-day chronic animal experiment was conducted with a calf. Five pulsatile studies were performed on the alert animal. The mean pump speed was set at 2800 rpm, and modulated sinusoidally within a range of 0 to ± 35% of mean speed, in increments of 5% at 80 beats per minute (bpm). The pressures and pump flow were collected and a pulsatility index (PI) was calculated. RESULTS: The calf was supported with the CFTAH100 without any major complications. The maximum and minimum pump flows changed significantly from baseline in all conditions, while the mean pump flow did not change. All flow pulsatility (FP) readings in all conditions significantly increased from baseline, and the percent modulation (%S) and FP had a strong positive correlation (r = 0.99, p < 0.01). The PI also increased significantly in all conditions (maximum at %S of 35%, 2.2 ± 0.05, p < 0.01), and a positive correlation between %S and PI (r = 0.99, p < 0.01) was observed. CONCLUSION: The CFTAH100 showed the feasibility of creating pulsatile circulation with sinusoidal pump speed modulation.

Evaluation of centrifugal blood pump performances for biventricular support in the virtual simulation model.

BACKGROUND: Despite the advances in the left ventricular assist device (LVAD), there are still situations that require a biventricular assist device (BVAD) system. The purpose of this study was to explore and compare the system performance interactions with the HeartMate3 (HM3) and HeartWare (HVAD) in a BVAD configuration using the virtual mock loop (VML) simulation tool. METHODS: The VML simulation tool is an in silico implementation of a lumped parameter model of the cardiovascular system with mechanical circulatory support. Patients with ejection fractions of 60%, 20%, and 15% were simulated in VML, and the HVAD and HM3 in a BVAD with ventricular cannulation were applied to simulated conditions. Pump speeds that restored baseline normal hemodynamics were determined. To determine the optimal speeds for BVAD, the left and right arterial pressures (LAP, RAP) were plotted. RESULTS: In the HVAD, LAP and RAP are balanced at 11 mm Hg with LVAD 3500 rpm, right ventricular assist device (RVAD) 2200 rpm; at 13 mm Hg with LVAD 3000 rpm, RVAD 1700 rpm; and at 14 mm Hg with LVAD 2500 rpm, RVAD 1300 rpm. For the HM3, at 8 mm Hg with LVAD 7000 rpm, RVAD 5000 rpm; at 9 mm Hg with LVAD 6000 rpm, RVAD 4300 rpm; and at 9.5 mm Hg with LVAD 5000 rpm, RVAD 3500 rpm. CONCLUSION: The RVAD/LVAD speed ratios required for atrial balance were approximately 0.6 for the HVAD and 0.7 for the HM3. However, the HVAD required RVAD speeds below its range of operation.

Large animal models of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and multiple comorbidities. The number of patients is continuously increasing, with no improvement in its unfavorable prognosis, and there is a strong need for novel treatments. New devices and drugs are difficult to assess at the translational preclinical step due to the lack of high-fidelity large animal models of HFpEF. In this review, we describe the summary of historical and evolving techniques for developing large animal models. The representative methods are pressure overload models, including (1) aortic banding, (2) aortic stent, (3) renal hypertension, and (4) mineralocorticoid-induced hypertension. Diet-induced metabolic syndromes are also used. A new technique with an inflatable balloon inside the left ventricle can be used during acute/chronic in vivo surgeries to simulate HFpEF-like hemodynamics for pump-based therapies. Canines and porcine are most widely used, but other non-rodent animals (sheep, non-human primates, felines, or calves) have been used. Feline models present the most well-simulated HFpEF pathology, but small size is a concern, and the information is still very limited. The rapid and reliable establishment of large animal models for HFpEF, and novel methodology based on the past experimental attempts with large animals, are needed.

Biventricular assist devices and total artificial heart: Strategies and outcomes.

In contrast to the advanced development of the left ventricular assist device (LVAD) therapy for advanced heart failure, the mechanical circulatory support (MCS) with biventricular assist device (BVAD) and total artificial heart (TAH) options remain challenging. The treatment strategy of BVAD and TAH therapy largely depends on the support duration. For example, an extracorporeal centrifugal pump, typically referred to as a temporary surgical extracorporeal right ventricular assist device, is implanted for the short term with acute right ventricular failure following LVAD implantation. Meanwhile, off-label use of a durable implantable LVAD is a strategy for long-term right ventricular support. Hence, this review focuses on the current treatment strategies and clinical outcomes based on each ventricle support duration. In addition, the issue of heart failure post-heart transplantation (post-HT) is explored. We will discuss MCS therapy options for post-HT recipients.

Efficacy of Plasma free Hemoglobin for detecting centrifugal pump thrombosis.

INTRODUCTION: Lactate dehydrogenase (LDH) is widely used as an indicator of pump thrombosis in a centrifugal pump. However, due to the low specificity of LDH, pump thrombosis is difficult to detect in the clinical environment. We measured plasma free hemoglobin (pfHb) with the portable device in ICU. The goal of this investigation is to evaluate its diagnostic ability for pump thrombosis. METHODS: We enrolled 31 consecutive patients who needed Extracorporeal Membrane Oxygenation (ECMO) therapy and pfHb was determined with HemoCue® plasma/Low Hb photometer. Pump thrombosis was analyzed macroscopically at the timing of pump explantation or exchange. Also, we divided the pump thrombosis into a grading scale by the place of thrombosis. RESULTS: The median of peak pfHb was significantly lower in the none thrombus group (0.03 g/dL) than that of in the thrombus group (0.05g/dL) (p = 0.01). In our grading criteria, pfHb was significantly higher when the thrombus is existing near the shaft (p = 0.015). Contrary, no significant difference was found for LDH.The ROC analysis of pfHb revealed an AUC of 0.77 for detecting pump thrombosis with the best statistical cutoff value at 0.05 g/dL (specificity, 78%; sensitivity, 77%). Also, ROC analysis of LDH was performed (AUC, 0.44; cutoff value, 1200 IU/L; specificity, 59%; sensitivity, 54%) and compared with pfHb. AUC was significantly higher in pfHb (p = 0.04). CONCLUSION: Our results showed the efficacy of pfHb for detecting centrifugal pump thrombosis.

Warfarin-induced toxic epidermal necrolysis after mitral valve replacement.

Stevens-Johnson syndrome and toxic epidermal necrolysis are rare diseases that cause acute destruction of the epithelium of the skin and mucous membranes, almost always attributable to drugs. However, warfarin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis is extremely rare. We report the case of 71-year-old woman who died due to destructive erosion all over her skin and mucous membranes. She had received a mitral valve prosthesis, and warfarin was prescribed for antithrombotic therapy. A lymphocyte transformation test for drug hypersensitivity and the clinical history confirmed this phenomenon as warfarin-induced toxic epidermal necrolysis.

Giant biatrial myxoma with two different gross findings.

We experienced a giant biatrial myxoma concomitant with hepatocellular carcinoma. Most of myxomas originate from the left atrium, and biatrial myxomas are extremely rare. Excision of the giant cardiac tumor was performed to avoid risks of life-threatening complications. The resected mass was grossly composed of two parts with the border of interatrial septum and with the shape of peanut shell. Although microscopic examinations revealed enlarged vessels, hemorrhages and hemosiderosis in the left part and high cellularity with chronic inflammation in the right part, spindle-shaped cells in a loose myxoid stroma were observed in both parts of the tumor, consistent with the diagnosis of myxoma. His second operation for hepatic cancer was successfully performed following 1 month after the first operation. Surgical treatment should be considered for giant atrium tumor which has risk of life-threatening complications even if patients have another cancer.

Entire Circumferential Reconstruction of the Right Atrium Surrounded by Angiosarcoma.

Primary cardiac angiosarcomas are frequently found at a large size with infiltration into the adjacent heart structure owing to their asymptomatic characteristics until an advanced stage. Therefore, extensive resection is often required to achieve a good prognosis. We herein report a case of entire circumferential resection of the right atrium surrounded by angiosarcoma and excellent three-dimensional reconstruction of the right atrium.