Continuous-flow total artificial heart port-to-port connection technique using dedicated de-airing sleeve.

Preventing the introduction of air while a mechanical circulatory support device is being implanted is critical for successful outcomes. A substantial amount of air may be introduced into the circulation during the pump-to-outflow and/or pump-to-inflow port connection, which can be detrimental to optimal pump function and long-term survival. We have developed a novel connecting sleeve that enables an airless connection of the continuous-flow total artificial heart to the conduits. Herein, we describe the device design and surgical techniques evaluated in vivo.

Decellularization of Whole Human Heart Inside a Pressurized Pouch in an Inverted Orientation.

The ultimate solution for patients with end-stage heart failure is organ transplant. But donor hearts are limited, immunosuppression is required, and ultimately rejection can occur. Creating a functional, autologous bio-artificial heart could solve these challenges. Biofabrication of a heart comprised of scaffold and cells is one option. A natural scaffold with tissue-specific composition as well as micro- and macro-architecture can be obtained by decellularizing hearts from humans or large animals such as pigs. Decellularization involves washing out cellular debris while preserving 3D extracellular matrix and vasculature and allowing "cellularization" at a later timepoint. Capitalizing on our novel finding that perfusion decellularization of complex organs is possible, we developed a more "physiological" method to decellularize non-transplantable human hearts by placing them inside a pressurized pouch, in an inverted orientation, under controlled pressure. The purpose of using a pressurized pouch is to create pressure gradients across the aortic valve to keep it closed and improve myocardial perfusion. Simultaneous assessment of flow dynamics and cellular debris removal during decellularization allowed us to monitor both fluid inflow and debris outflow, thereby generating a scaffold that can be used either for simple cardiac repair (e.g. as a patch or valve scaffold) or as a whole-organ scaffold.

Artificial organs 2014: a year in review.

In this Editor's Review, articles published in 2014 are organized by category and briefly summarized. We aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ Replacement, Recovery, and Regeneration. As the official journal of the International Federation for Artificial Organs, the International Faculty for Artificial Organs, the International Society for Rotary Blood Pumps, the International Society for Pediatric Mechanical Cardiopulmonary Support, and the Vienna International Workshop on Functional Electrical Stimulation, Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level." Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide meaningful suggestions to the author's work whether eventually accepted or rejected. Without these excellent and dedicated reviewers, the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, John Wiley & Sons, for their expert attention and support in the production and marketing of Artificial Organs. We look forward to reporting further advances in the coming years.

Japanese guidance for ventricular assist devices/total artificial hearts.

To facilitate research and development (R&D) and to expedite the review processes of medical devices, the Ministry of Health, Labor and Welfare (MHLW) and the Ministry of Economy, Trade and Industry (METI) founded a joint committee to establish guidance for newly emerging technology. From 2005 to 2007, two working groups held discussions on ventricular assist devices and total artificial hearts, including out-of-hospital programs, based on previous guidance documents and standards. Based on this discussion, the METI published the R&D Guidelines for innovative artificial hearts in 2007, and in 2008 the MHLW published a Notification by Director regarding the evaluation criteria for emerging technology.

[Actual role of cardiocirculatory assistance in heart failure treatment]. / Ruolo attuale dell'assistenza cardiocircolatoria nel trattamento dell'insufficienza cardiaca.

Patients with end-stage heart failure have poor quality of life and a poor prognosis. These patients are usually burdened by symptoms at rest, the need for frequent hospital admissions, complex pharmacological therapies and a 1-year mortality rate of about 50%. Therapeutic options are scarce and not available for all. Only few patients can be transplanted. Alternative medical and surgical therapies have shown limited ability to influence prognosis and quality of life. In the past years, technological progress has brought to the clinician mechanical devices capable of providing short/medium and long-term circulatory assistance. Clinical evidence of long-term survival without device-correlated adverse events using last generation small axial pumps, allows us to evaluate its use in patients with contraindications or inaccessibility to transplantation.

Device therapy and cardiac transplantation for end-stage heart failure.

The prevalence of heart failure is increasing, and the prognosis of end-stage heart failure remains dismal. The gold-standard therapy in end-stage heart failure remains cardiac transplantation at the present time, but there is a great excess of eligible candidates compared with the number of donor organs. Advances in mechanical support, the development of the left ventricular assist device (LVAD), and the total artificial heart has reduced mortality and morbidity in patients awaiting transplantation, and LVADs are now approved as an strategy for destination therapy. Miniaturization, increased device durability, and complete implantability may render LVADs an option in earlier stages of heart failure, as a bridge to myocardial recovery or even as a viable alternative to transplantation. Alternative strategies under investigation are cell therapy and xenotransplantation. In the present article, current and potential future therapeutic options in end-stage heart failure are reviewed.

In vivo acute performance of the Cleveland Clinic self-regulating, continuous-flow total artificial heart.

BACKGROUND: The purpose of this study was to evaluate the acute in vivo pump performance of a unique valveless, sensorless, pulsatile, continuous-flow total artificial heart (CFTAH) that passively self-balances left and right circulations without electronic intervention. METHODS: The CFTAH was implanted in two calves, with pump and hemodynamic data recorded at baseline over the full range of pump operational speeds (2,000 to 3,000 rpm) in 200-rpm increments, with pulsatility variance, and under a series of induced hemodynamic states created by varying circulating blood volume and systemic and pulmonary vascular resistance (SVR and PVR). RESULTS: Sixty of the 63 induced hemodynamic states in Case 1 and 73 of 78 states in Case 2 met our design goal of a balanced flow and maximum atrial pressure difference of 10 mm Hg. The correlation of calculated vs measured flow and SVR was high (R(2) = 0.857 and 0.832, respectively), allowing validation of an additional level of automatic active control. By varying the amplitude of sinusoidal modulation of the speed waveform, 9 mm Hg of induced pulmonary and 18 mm Hg of systemic arterial pressure pulsation were achieved. CONCLUSIONS: These results validated CFTAH self-balancing of left and right circulation, induced arterial flow and pressure pulsatility, accurate calculated flow and SVR parameters, and the performance of an automatic active control mode in an acute, in vivo setting in response to a wide range of imposed physiologic perturbations.

Total artificial heart--concepts and clinical use.

End-stage congestive heart failure remains the leading cause of death in the United States. Despite advances in medical treatment, it also remains the most common reason for admission to the hospital. The gold standard of treatment for the failing heart, orthotopic heart transplantation, is limited by a shortage of donor hearts. There are also a significant number of patients who are not transplant candidates due to comorbid conditions and/or inability to tolerate immunosuppressive therapy. To meet the need for this latter group, the medical field has embraced ventricular assist device (VAD) therapy to extend survival and improve quality-of-life for the end-stage cardiac patient. This therapy, however, has been currently limited to the failing left ventricle and is still fraught with complications that limit long-term and widespread use. The total artificial heart, as currently available with two devices, is rapidly becoming the treatment of choice for biventricular failure.

[Artificial heart].

Artificial heart or heart transplantation are required for the treatment of profound heart failure. Total artificial heart (TAH) and ventricular assist system (VAS) were developed from late 1950s and 2 extracorporeal pneumatic Japanese VASs (Toyobo VAS and Zeon VAS) were introduced to clinical field from 1980. Now, over 850 patients were applied several types of VASs including Japanese VASs. And 80% of heart transplant recipients were supported by VASs for 714 days (mean). Small size implantable left VAS (LVAS) are required and several types of non-pulsatile pump, including 2 Japanese made centrifugal pumps, are under clinical trials. And destination therapy by using implantable pulsatile LVAS for end-stage heart failure patients has been started in United States and is performed in United States and Europe. In near future, artificial heart and heart transplantation will be selected according to the conditions of the patients with profound heart failure.

[The results of the artificial heart]. / Les résultats du coeur artificiel.

The artificial heart is no more a dream but a reality. Over the last 40 years, many circulatory assist devices have been developed. First were the pneumatic devices, external or implantable, providing uni- or biventricular support; next were the partially implantable electromecanical devices. We went from the first generation of devices with all components (pump, energy power, control system) outside of the body to the second generation of devices with the pump and the motor implanted inside the body. Recently, the third generation of artificial hearts appeared with all components implanted inside the body allowing better mobility and quality of life. Results depend on the indication and on the kind of artificial heart implanted: partial (native heart still in place) or total (native heart removed). Essentially developped as a bridge to transplant, the artificial heart is now allowed as destination therapy.

Mechanism for cavitation of monoleaflet and bileaflet valves in an artificial heart.

It is possible that mechanical heart valves mounted in an artificial heart close much faster than those used for clinical valve replacement, resulting in the formation of cavitation bubbles. In this study, the mechanism for mechanical heart cavitation was investigated using the Medtronic Hall monoleaflet valve and the Sorin Bicarbon bileaflet valve mounted at the mitral position in an electrohydraulic total artificial heart. The valve-closing velocity was measured with a charge-coupled device (CCD) laser displacement sensor, and images of mechanical heart valve cavitation were recorded using a high-speed video camera. The valve-closing velocity of the Sorin Bicarbon bileaflet valve was lower than that of the Medtronic Hall monoleaflet valve. Most of the cavitation bubbles generated by the monoleaflet valve were observed near the valve stop; with the Sorin Bicarbon bileaflet valve, cavitation bubbles were concentrated along the leaflet tip. The cavitation density increased as the valve-closing velocity and the valve stop area increased. These results strongly indicate that squeeze flow holds the key to cavitation in the mechanical heart valve. From the perspective of squeeze flow, bileaflet valves with a low valve-closing velocity and a small valve stop area may cause less blood cell damage than monoleaflet valves.

A review of leakage flow in centrifugal blood pumps.

This article presents a new approach in determining the functional relationship between the leakage flow in a centrifugal blood pump and various parameters that affect it. While high leakage flow in a blood pump is essential for good washout and can help prevent thrombus formation, excessive leakage flow will result in higher fluid shear stress that may lead to hemolysis. Dimensional analysis is employed to provide a functional relationship between leakage flow rate and other important parameters governing the operation of a centrifugal blood pump. Results showed that pump performance with a smaller gap clearance is clearly superior compared to those of two other similar pumps with larger gap clearances. It was also observed that the nondimensional leakage flow rate varies almost linearly with dimensionless pump head. It also decreases with increasing volume flow rate. A smaller gap clearance will also increase the flow resistance and hence, decrease the nondimensional leakage flow rate. Increasing surface roughness, length of the gap clearance passage, or loss coefficient of the gap geometry will increase losses and hence, decrease the leakage flow rate. It is also interesting to note that for a given pump and gap clearance geometry, the nondimensional leakage flow rate is almost independent of the Reynolds number when specific speed is constant.

[Bio-artificial organs: cardiac applications]. / Bio-artificiële organen: cardiale toepassingen.

The most important bio-prosthetic organs in cardiovascular medicine are artificial heart valve prostheses and blood pumps. Cardiac valve prostheses can be divided in 'mechanical' and 'biological' valves. Mechanical prostheses are entirely made of artificial materials and require a meticulous anticoagulation therapy. The biological heart valves or heterografts (the allo- and autografts are not considered in this issue) are made of fixed or crosslinked biological tissue and therefore anticoagulation of the patient is not necessary. Actual mechanical heart valves consist of a titanium ring in which one or more leaflets made of pyrolite carbon assure the opening and closing mechanism. Biological heart valves are made of fixed porcine aortic valves or of fixed bovine pericardium. Both tissues can be mounted on a metal frame (so-called 'stented valves') or they can lack this structure ('stentless valves'). The problem with these biological valves is the durability: during the years they start degenerating or calcifying. To prevent this, recent biological heart valves are treated with an anti-mineralisation procedure. Since recent years intense research is ongoing to develop a living heart valve by 'tissue engineering'. When the entire heart fails, and pharmacological treatment remains inadequate or a heart transplantation is not immediately possible, artificial blood pumps are implanted. In general, two categories of blood pumps can be distinguished: displacement and rotary blood pumps. Displacement pumps move a certain amount of blood by the movement of a flexible membrane. This movement is pneumatically or electrically driven and requires an extensive installation: artificial ventricles, tubing, motors, pneumatic systems and driving consoles. Examples in clinical use are: Novacor, Heart Mate, Thoratec, Medos/HIA. Recent developments focus on miniaturisation and endovascular implantation. The rotary blood pumps are well suited for these purposes. They can be either axial, diagonal or radial pumps. A promising new develoment is the Impella pump: this is an axial flow pump having a diameter of 4 mm, which is implanted, inclusive the electrical motor, in the failing heart and delivers an output of 2 to 10 liter/minute. Clinical testing of this device is ongoing.

Resonant frequency control for artificial heart using online parameter identification.

To develop effective medical care and therapeutic control using an artificial heart, a new control method has been developed. This new method can control the artificial heart effectively and can adapt to internal physiological behavior using measured physiological data; aortic pressure, aortic flow, and pump flow. This method consists of first, a second-order physiological model, which represents the internal physiological behavior by a mathematical equation; and second, an estimation method, which can identify the physiological parameters; aortic inertia, aortic resistance, aortic compliance, and peripheral resistance by a parameter identification method. It can then calculate the resonant frequency as the control signal for the artificial heart from the identified physiological model. To confirm the effectiveness, the proposed method was evaluated in a computer simulation study. This evaluation showed that the new method could estimate the physiological parameters and the resonant frequency within a 10% error. The impedance of the systemic circulation could also be reduced by this method.

AbioCor totally implantable artificial heart. How will it impact hospitals?

Although heart transplantation remains the most effective treatment for severe heart failure, there are far fewer donor hearts available than there are patients who could benefit from them. One approach to addressing this shortfall is the total artificial heart, or TAH. To date, however, no TAH design has been able to achieve one of the ultimate goals of heart replacement: to allow a patient to live a reasonably normal life without being connected to external machinery. A new design, the AbioCor TAH developed by Abiomed Inc., may make this goal achievable. Thanks to a power system that transfers energy through the skin without the aid of wires, the AbioCor--currently undergoing clinical trials in the United States--allows the patient to be completely mobile. The lack of transcutaneous wires also eliminates the primary source of the infections that have plagued TAH patients in the past. Though it is not without drawbacks, the AbioCor could represent a crucial advance in TAH technology. In this Technology Overview, we describe the operation of the AbioCor and discuss its likely impact on hospitals if it is approved for marketing in the United States. We also discuss a related cardiac-support technology: ventricular assist devices (VADs), which may also be used for permanent cardiac support someday.

Current options for mechanical heart technology.

Heart transplantation remains the treatment of choice for end-stage heart failure despite limited donor availability and allograft durability. Artificial heart technology was initially developed as a replacement for transplantation but the initial experience with these technologies was disappointing. The quest for a total artificial heart has largely been abandoned in favor of ventricular assist devices (VADs). VADs have gained widespread acceptance as bridge to transplant and bridge to recovery therapy. After more than a decade of clinical use, several FDA approved device designs have proved effective in treating patients with various causes of heart failure. This review describes the current, clinically available ventricular replacement and assist devices and defines the adult patient populations in which they are useful. The next generation of these devices will soon become available and their clinical utility will likely shape the future direction of heart failure therapy. Ultimately the concept of a long-term total artificial heart may be revisited.