Sotirios Spiliopoulos

System overview of the fully implantable destination therapy—ReinHeart-total artificial heart

OBJECTIVES Owing to the lack of suitable allografts, the demand for long-term mechanical circulatory support in patients with biventricular end-stage heart failure is rising. Currently available Total Artificial Heart (TAH) systems consist of pump units with only limited durability, percutaneous tubes and bulky external equipment that limit the quality of life. Therefore we are focusing on the development of a fully implantable, highly durable destination therapy total artificial heart. METHODS The ReinHeart-TAH system consists of a passively filling pump unit driven by a low-wear linear drive between two artificial ventricles, an implantable control unit and a compliance chamber. The TAH is powered by a transcutaneous energy transmission system. The flow distribution inside the ventricles was analysed by fluid structure interaction simulation and particle image velocimetry measurements. Along with durability tests, the hydrodynamic performance and flow balance capability were evaluated in a mock circulation loop. Animal trials are ongoing. RESULTS Based on fluid structure interaction simulation and particle image velocimetry, blood stagnation areas have been significantly reduced. In the mock circulation loop the ReinHeart-TAH generated a cardiac output of 5 l/min at an operating frequency of 120 bpm and an aortic pressure of 120/80 mmHg. The highly effective preload sensitivity of the passively filling ventricles allowed the sensorless integration of the Frank Starling mechanism. The ReinHeart-TAH effectively replaced the native hearts function in animals for up to 2 days. CONCLUSIONS In vitro and in vivo testing showed a safe and effective function of the ReinHeart-TAH system. This has the potential to become an alternative to transplantation. However, before a first-in-man implant, chronic animal trials still have to be completed.

HeartMate II ventricular assist device thrombosis-an echocardiographic approach to diagnosis: can Doppler evaluation of flow be useful?

A 68-year-old man was admitted to the hospital 4 months after HeartMate II ventricular assist device implantation, because his clinical status had deteriorated and his levels of lactate dehydrogenase and free hemoglobin had increased. Transthoracic echocardiography performed at admission revealed decreased basic diastolic continuous flow velocity with a pulsatile increase in flow velocity during ventricular contraction in both inflow and outflow cannulas. Twelve hours after beginning lytic therapy, basal diastolic continuous flow velocity had increased, and the amplitude between diastolic and systolic flow velocity had decreased. The clinical status of the patient improved, and his lactate dehydrogenase decreased. A decrease in basal diastolic flow may be a valuable marker of flow disturbance in continuous flow ventricular assist devices.

Image based evaluation of mediastinal constraints for the development of a pulsatile total artificial heart.

BackgroundGood anatomical compatibility is an important aspect in the development of cardiovascular implants. This work analyzes the interaction of the pump unit of an electrically driven pulsatile Total Artificial Heart (TAH) and the mediastinum. For an adequate compliance, both overall dimensions and alignment of inlets and outlets must be matched.MethodsCross-sectional medical image data of 27 individuals, including male and female patients suffering from end stage heart failure, was segmented and reconstructed to three dimensional (3D) surface models. Dimensions and orientations of relevant structures were identified and analyzed. The TAH surface model was virtually placed in orthotopic position and aligned with atrioventricular valves and big vessels. Additionally seven conventional cadaver studies were performed to validate different pump chamber designs based on virtual findings. Thereby 3D-coordinates were captured and introduced to the virtual environment to allow quantitative comparison between different individuals.ResultsSpatial parameters varied more in male patients with higher values if heart failure persists. Good correlation of the virtual analysis both to literature data and conventional cadaver studies could be shown. The full data of the 27 individuals as well as the summarized values found in literature are enclosed in the appendix. By superimposing the TAH-volume model to the anatomy, various misalignments were found and the TAH-design was adjusted.ConclusionsVirtual fitting allows implant design adjustments in realistic anatomy which has not been influenced by thoracotomy. Higher numbers of relevant individuals can be reasonably investigated in the virtual environment and quantitatively correlated. Using this approach, conventional cadaver studies can be significantly reduced but not obviated, due to the unavailable haptic feedback and immobility of potentially compressed structures.

New experience with the paracardial right ventricular axial flow micropump impella elect 600

Beating heart surgery is still challenging and could be made safer using assisted circulation. We evaluated clinical outcome following beating heart myocardial revascularisation using the impella elect system with intracardial left ventricular (LV) and paracardial right ventricular (RV) microaxial pumps in eight patients. Clinical course was uneventful. There were no device-related complications. The paracardial design of the RV-pump is a great advantage compared to the former intracardial design because it eliminates arrhythmia and LV hypovolemia. Support by microaxial pumps can make beating heart surgery safer and applicable for more complex cases.

Paving the way for destination therapy of end-stage biventricular heart failure: the ReinHeart total artificial heart concept.

The rising demand for cardiac transplantation and the steady decline in the number of instances of organ donation pose a serious challenge to physicians dealing with biventricular end-stage heart failure. Total artificial heart (TAH) therapy is therefore an alternative of growing importance. Three systems are currently available: The SynCardia-TAH (SynCardia Systems, Inc., Tucson, AZ, USA), the AbioCor-TAH (Abiomed, Inc., Danvers, MA, USA) and since recently the CARMAT-TAH (Carmat SA, Velizy Villacoublay, France). The ‘SynCardia’ is the only TAH system widely available. In addition to being a bridge to transplant [1, 2], the US Food and Drug Administration (FDA) recently approved a Humanitarian Use Device designation for the SynCardia-TAH for its use for destination therapy (DT) in patients not eligible for transplantation [3]. The limitations of this technology are mechanical parts that are prone to wear and tear, the need for percutaneous tubes and dependence on a permanent external driver. The ‘AbioCor-TAH’ was the first totally implantable, electrically driven TAH, designed as an alternative to cardiac transplantation. Although approved under the Humanitarian Device Exemption program in 2006, the device is currently not implanted due to its limited clinical success [4]. Finally, the ‘CARMAT’ is a fully implantable, electrohydraulically driven, pulsatile flow device with four bioprosthetic valves. Its artificial ventricles consist of processed bioprosthetic pericardial tissue and expanded polytetrafluorethylene [5]. The first-in-man implant was performed in 2013. The duration of support was 74 days. The feasibility trial is still ongoing. Durability and maintenance-free operation are essential requirements incorporated into any TAH design to facilitate long-term support. Reliable operation and broad applicability depend on small dimensions of the pump unit, low weight, low thermal losses, minimal haemolysis and thrombogenicity, sufficient pumping capacity and redundancy in all possible system components. These requirements are addressed by the ‘ReinHeart’ (Fig. 1). This is an electrically driven TAH currently being developed on this basis by our institutions. It is designed as an alternative to heart transplantation and aimed to support patients for at least 5 years. The size of the pump unit and the orientation of the inand outlets have been optimized according to anatomical and virtual fit studies [6]. A first major characteristic of the ReinHeart concept is the application of a linear motor concept that diminishes the need for wearprone components such as ball-bearings, gears and lubricants, increasing the durability and reliability of the pump unit. The linear motor is directly connected to a left and a right pusher plate, guided by a single linear bearing. The pusher plates are actuated in an alternating way, pumping the blood out of the chambers in a physiological sinusoidal pattern. The chambers consist of highly biocompatible transparent methacrylate–acrylonitrile–butadiene– styrene thermoplastic copolymer. Four mechanical valves (St Jude Medical, Inc.; St Paul, MN, USA) facilitate unidirectional blood flow. A second major characteristic of the ReinHeart is that the pump chambers are not mechanically attached to the pusher plates, enabling a preload sensitive filling and consequently ejection of the ventricles. This allows a robust implementation of a starling-like behaviour similar to the natural heart. In contrast to the AbioCor and the CARMAT-TAHs, vulnerable pressure sensors are not required for this purpose. Depending on operational frequency and preload, the artificial ventricles can generate a pump flow of up to 7.5 l/min. Figure 2 gives an overview of the system components. The implanted components are the pump unit, an implantable controller, a transcutaneous energy transmission (TET) system and a compliance chamber that optimizes ventricular filling. External patient equipment consists of the primary TET coil and a user interface with batteries. The TET system supports the device up to a distance of 30 mm. The batteries are charged by connecting the outer coil of the TET system and can operate the device for 45 min at full capacity. Total implantability of the system components facilitates increased patient mobility and silent operation, thus contributing to a significantly increased quality of life.

A monitoring and physiological control system for determining aortic valve closing with a ventricular assist device

OBJECTIVES Real-time monitoring of the aortic valve function and the loading state of the left ventricle (LV) during mechanical circulatory support is essential. Therefore, we developed a system that determines accurately the aortic valve closing moment based on integrals derived from the pump inlet pressure and the pump power [pressure-power area (PPA)]. METHODS A Deltastream diagonal pump was implanted in 10 healthy Rhoen sheep. Changes in ventricular volume and pressure in different assist levels were measured by a conductance catheter placed in the LV and were correlated with intrinsic pump signals, motor power, voltage and current. Measurements were obtained in the state of normal as well as decreased left ventricular contractility induced by β-blockers. RESULTS Complete datasets were obtained in seven animals. The PPA-feedback signal reached its maximum at the speed of aortic valve closing. This was validated by pressure-volume (PV)-catheter measurements both at the baseline and in the state of decreased contractility. In both cases, zero-crossing occurred at the point of aortic valve closing speed. CONCLUSIONS With this trial, we deliver the experimental basis for the development of an automatic feedback controller that would allow periodic speed changes in accordance with the loading state of the native ventricle and the opening state of the aortic valve. This would deliver real-time data to treating physicians and enable the establishment of a standard weaning protocol.

A Novel Total Artificial Heart for Destination Therapy: In-Vitro and In-Vivo Study.

Total Artificial Hearts (TAHs) could be used as an alternative to heart transplantation for patients with terminal heart failure. A fully implantable TAH is under development at our institute. Some critical aspects in TAH development are a) sufficient cardiac output, b) adequate left-right flow balance, c) measurement and control of pump performance and d) hemocompatibility. In this paper, the results of the validation process including in vitro, acute and first chronic in vivo experiments are presented.

Delayed sternal closure after total artificial heart implantation

Data represent numbers of patients except as noted. Statistical comparisons were made by 2-tailed t test. RBC, Red blood cell; FFP, fresh-frozen plasma. One of the issues of greatest concern in total artificial heart (TAH) therapy is excessive bleeding in the early postoperative setting. Impaired perfusion, in cases of extended myocardial infarction and cardiogenic shock, and increased filling pressures, in cases of chronic biventricular heart failure, result in hepatic dysfunction and coagulation disorders. It is therefore not surprising that reexploration rates are still high. Although delayed sternal closure (DSC) is a well-established option for the management of refractory bleeding after routine and especially pediatric cardiac surgery, its safety and efficacy have still not been evaluated in the context of TAH therapy.

Expanding Applicability of Total Artificial Heart Therapy: The 50-cc SynCardia Total Artificial Heart

The 50-cc SynCardia total artificial heart is designed to facilitate orthotopic replacement of the native ventricles in patients with a body surface area below 1.7 m(2) in need of long-term circulatory support as a result of end-stage biventricular heart failure. We describe the implementation of this technology in a female patient with irreversible cardiogenic shock on the grounds of acute myocardial infarction and chronic ischemic cardiomyopathy.

B-type natriuretic peptide therapy in total artificial heart implantation: Renal effects with early initiation

B-type natriuretic peptide (BNP) is produced mainly by ventricular myocytes and to a lesser degree by cardiac fibroblasts. In the context of end-stage heart failure, chronic myocyte stretch upregulates BNP and intracellular cyclic GMP synthesis, thus inducing vasodilation, diuresis and inhibition of the renin–aldosterone system. In the case of total artificial heart (TAH) implantation, resection of the native ventricles results in a rapid decrease of endogenous BNP production and interruption of these signaling pathways. Consequently, renal function declines. Low-dose BNP infusions have been proven to have a positive impact on urine output in the early post-operative setting. However, due to the lack of large-study experience, optimal timing of BNP therapy is still unclear. Because prevalence of chronic renal failure in TAH candidates is high, we hypothesized that early initiation of low-dose BNP infusion therapy in all patients would help avoid low urine output events and diminish the need for renal replacement therapy. Between January and November 2013, 12 patients received a SynCardia TAH. Two patients with dialysis-dependent endstage renal failure due to diabetic nephropathy were excluded