Heart failure (HF) affects an estimated 5.8 million Americans, accounting for near 250,000 deaths each year. With shortages in available donor hearts, mechanical circulatory support (MCS) has emerged as a life-saving treatment for advanced stage HF. With growth in MCS use, a clinical and developmental need has emerged for a standard characterization and evaluation platform that may be utilized for inter-device comparison and system training. The goal of this research was to harness SynCardia's total artificial heart (TAH) to meet this need. We first sought to characterize the TAH in modern physiological terms - i.e. hemodynamics and pressure-volume loops. We then developed a model of HF using the TAH and mock circulatory system operating in a reduced output mode. We demonstrated that MCS devices could be incorporated and evaluated within the HF model. Finally, we characterized the operational envelope of SynCardia's Freedom (portable), Driver operating against varying loading conditions. Our results describe the hemodynamic envelope of the TAH. Uniquely, the TAH was found not to operate with time-varying elastance, to be insensitive to variations in afterload up to at least 135 mmHg mean aortic pressure, and exhibit Starling-like behavior. After transitioning the setup to mimic heart failure conditions, left atrial pressure and left ventricular pressure were noted to be elevated, aortic flow was reduced, sensitivity to afterload was increased, and Starling-like behavior was blunted, consistent with human heart failure. The system was then configured to allow ready addition of ventricular assist devices, which upon placement in the flow circuit resulted in restoration of hemodynamics to normal. Lastly, we demonstrated that the Freedom Driver is capable of overcoming systolic pressures of 200 mmHg as an upper driving limit. Understanding the physiology and hemodynamics of MCS devices is vital for proper use, future device development, and operator training. Characterization of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared to the human heart. The use of the system as a heart failure model has the potential to serve as a valuable research and teaching tool to foster safe MCS device use.

No description available.

Introduction: Cardiogenic shock due to myocardial infarction or heart failure entails a reduction in end organ perfusion. Patients who cannot be stabilized with inotropes and who experience increasing circulatory failure are in need of an extracorporeal mechanical support system. Today, small, percutaneously implantable cardiac assist devices are available and might be a solution to reduce mortality and complications. A temporary, ventricular, continuous flow propeller pump using magnetic levitation (Impella®) has been approved for that purpose. Methods and Study Design: JenaMACS (Jena Mechanical Assist Circulatory Support) is a monocenter, proof-of-concept study to determine whether treatment with an Impella CP® leads to improvement of hemodynamic parameters in patients with cardiogenic shock requiring extracorporeal, hemodynamic support. The primary outcomes of JenaMACS are changes in hemodynamic parameters measured by pulmonary artery catheterization and changes in echocardiographic parameters of left and right heart function before and after Impella® implantation at different support levels after 24 h of support. Secondary outcome measures are hemodynamic and echocardiographic changes over time as well as clinical endpoints such as mortality or time to hemodynamic stabilization. Further, laboratory and clinical safety endpoints including severe bleeding, stroke, neurological outcome, peripheral ischemic complications and occurrence of sepsis will be assessed. JenaMACS addresses essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and improve the outcome in those patients. Conclusion: The JenaMACS study will address essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® assist device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and may improve outcome in those patients. Ethics and Dissemination: The protocol was approved by the institutional review board and ethics committee of the University Hospital of Jena. Written informed consent will be obtained from all participants of the study. The results of this study will be published in a renowned international medical journal, irrespective of the outcomes of the study. Strengths and Limitations: JenaMACS is an innovative approach to characterize the effect of additional left ventricular mechanical unloading during cardiogenic shock via a minimally invasive cardiac assist system (Impella CP®) 24 h after onset and will provide valuable data for acute interventional strategies or future prospective trials. However, JenaMACS, due to its proof-of-concept design, is limited by its single center protocol, with a small sample size and without a comparison group.

No description available.

Mechanical Circulatory Support (MCS) improves the health-related quality of life (HRQOL) for patients with end-stage heart failure (HF) (Friedrich & Bohm, 2007). Religious and spiritual practices positively influence health and well-being for cardiac patients (Ai, Park, Huang, Rodgers, & Tice, 2007; Blackhall, & Koenig, 1998). The purpose of this study was to examine the impact of spiritual well-being (SWB) and religious well-being (RWB) and coping styles and methods (CSM) on health related quality of life (HRQOL) of patients with MCS. This exploratory repeated measures study used Spearmans’ rho and Wilcoxons’ Signed Rank tests for correlation and comparison analyses. The study population included patients with left ventricular assist devices (HMII) and total artificial hearts (TAH). Patients were assessed pre and post MCS implant. Patients reported an increase in the use of faith practices for coping (prayer and meditation), providing evidence for spiritual growth after MCS. SWB, RWB, and CSM, and their corresponding subscales were positively related to HRQOL revealing medium to large correlation coefficients and variances. Post MCS, the TAH patients’ mean scores decreased for SWB and RWB (religious comfort) and increased for RWB (religious strain), indicating some spiritual distress. The internal locus of control for TAH patients increased with significance. HMII patients reported a significant increase in adaptive coping and “God” locus of control. The results suggest that early spiritual assessment with MCS patients may promote more timely and effective responses to maladaptive and dysfunctional coping. Patients who use their faith to cope (in distress or not) may also benefit from an increase in emotional and spiritual attention. Spiritual care providers who are knowledgeable about the MCS assessment, surgery, and recovery process could then provide interventions that build resilience and mediate improved outcomes through supportive and directed counseling. The results of this study inform the future development of interdisciplinary plans of spiritual and emotional care for this patient population and for other chronic illness populations. Further examination may reveal how SWB, RWB and CSM improve HRQOL as well as highlight the unique support needs of HMII and TAH patients.

Die vorliegende Untersuchung stellt sich die folgenden Fragen: Welchen Stand hat die Entwicklung von mechanischen Kreislaufunterstützungssystemen für Kinder, worin unterscheiden sich die eingesetzten Verfahren? Wie beeinflusst der Blutkontakt mit Fremdmaterial das Kapillarleck beim Kind? Welche Erfahrungen gibt es mit dem pulsatilen Ventrikelunterstützungssystem Berlin Heart beim Kind, welche Schwierigkeiten und Nebenwirkungen sind für das Kindesalter spezifisch? Wann profitieren Kinder von einer mechanischen Kreislaufunterstützung? Die bei Kindern am häufigsten eingesetzten Verfahren, Herzlungenmaschine (HLM), extrakorporale Membranoxygenierung (ECMO) und pneumatisch pulsatiles ventrikuläres Assist device (VAD) unterscheiden sich in Technik, Indikation, Nebenwirkung und möglicher Einsatzdauer erheblich. Die HLM dient der intraoperativen Kreislaufunterstützung. ECMO haben wir seit 1990 zur mittelfristigen Kreislaufunterstützung bei mehr als 70 Kindern für eine Dauer von ein bis zwei, selten bis zu drei Wochen eingesetzt. Mit VAD''s haben wir seit 1990 bei 56 Kindern die Herzfunktion teils monatelang ersetzt. Es bestehen multiple Unterschiede bei dem Einsatz von VAD zwischen Säuglingen, Kindern und Erwachsenen sowohl in der Indikation, Physiologie, Technik, Antikoagulation, der Familienbetreuung und hinsichtlich der Komplikationen. Bei jeder mechanischen Kreislaufunterstützung aktiviert der Fremdflächenkontakt des Blutes das Kontaktsystem, zu dem Gerinnungs- und Komplementsystem gehören. Klinische Äquivalente sind Thrombosen, Thrombozytenverlust und Kapillarleck. Insbesondere Säuglinge neigen zu diesen Komplikationen, weil das Verhältnis von Blutvolumen zu Fremdfläche ungünstig ist und der kontaktabhängige alternative Weg der Komplementaktivierung im jungen Alter vorherrscht. - Wir untersuchten prospektiv den prä- und postoperativen Verlauf von Kontakt- und Komplementsystem (C1q, C3, C4, C1-Inhibitor, Faktor B, Faktor XIIa) bei 11 herzoperierten Säuglingen ohne und 24 Säuglingen mit HLM. Es konnte nachgewiesen werden, dass obwohl bei allen Kindern eine Komplementaktivierung vorhanden war, diese signifikant ausgeprägter in der HLM-Gruppe stattfand. Die Kontaktaktivierung (Faktor XIIa, Präkallikrein) ließ sich nur in der HLM-Gruppe nachweisen, so dass belegt war, dass es nicht die Anästhesie oder die Operation an sich, sondern die HLM ist, die die inflammatorische Reaktion hervorruft. - Bei 27 mit HLM operierten Säuglingen untersuchten wir prospektiv die CLS-Entstehung und die Komplement- und Kontaktaktivierung. Bei den 10 Kindern, die im späteren Verlauf ein Kapillarlecksyndrom (CLS) entwickelten, waren bereits 30 Minuten nach HLM-Beginn die C1-INH-Konzentration und -Aktivität niedriger und Faktor XIIa, C3a und C5a höher als bei den 17 Kindern, die später kein CLS entwickelten. Die Aktivierung korrelierte mit dem Alter der Kinder und der HLM-Zeit, nicht mit der Tiefe der Hypothermie. - Retrospektiv untersuchten wir 28 Kinder (6 Tage - 16 Jahre alt), bei denen im terminalen Herzversagen nach Reanimation die Herzfunktion mit dem parakorporalen pneumatischen VAD Berlin Heart 1-98 Tage lang unterstützt wurde. Zwölf dieser Kinder wurden unter laufender Reanimation mit Herzdruckmassage in den Operationssaal gebracht. 13 Patienten erreichten eine Herztransplantation, 3 Kinder wurden mit dem eigenen Herzen vom System entwöhnt. 12 Kinder starben am System, Todesursachen waren Schock, Multiorganversagen, Sepsis und Blutungen. - Bei 95 herztransplantierten Kindern untersuchten wir retrospektiv die Verläufe in Abhängigkeit davon, ob die Kinder (I) vor der Transplantation in relativ stabilem Zustand zuhause waren (n=33), ob sie (II) kritisch krank hospitalisiert waren (n= 44), oder ob sie (III) nach Reanimation mit einem VAD kreislaufunterstützt wurden (n=18, Dauer 4-111 Tage). Die Überlebensraten nach 1Mo/1J/5J betrugen in Gruppe I 88/88/80 %, Gruppe II 88/82/79 %, Gruppe III 72/72/72 %. Der frühpostoperative Verlauf nach Transplantation war bei Gruppe III nur wenig komplizierter, was den Erfolg der Transplantation nicht minderte. - Retrospektiv untersuchten wir den Verlauf von 4 Kindern mit schwerer Myokarditis, die bei kardiogenem Schock mit biventrikulärem VAD kreislaufunterstützt wurden. Das schockbedingte Multiorganversagen und die Thrombozytopenie bildete sich während der Unterstützung mit dem VAD zurück. Drei Kinder konnten nach Erholung des Myokards vom VAD entwöhnt werden, eines wurde erfolgreich transplantiert. - Ausserdem untersuchten wir den Verlauf von 84 Kindern, die wegen Kardiomyopathie auf der Intensivstation behandelt wurden. Von den 69 (= 82 %), bei denen eine kreislaufstützende medikamentöse Therapie ausreichend war, konnten 32 herztransplantiert werden, 36 besserten sich und wurden nach Hause entlassen und ein Kind verstarb akut. Fünfzehn der 84 Kinder (= 18 %) ließen sich nicht stabilisieren und erhielten nach Reanimation eine mechanische Kreislaufunterstützung mit VAD (Dauer 1 – 98 Tage). Von diesen konnten 12 transplantiert werden. Die in dieser Habilitationsschrift ausgeführten Arbeiten haben weiterführende Fragestellungen und Grenzbereiche des mechanischen Kreislaufersatzes im Kindesalter aufgezeigt und neue Therapiestrategien dargestellt. Dadurch ist es möglich, die Überlebenschancen von Kindern mit terminalem Herzversagen erheblich zu verbessern. Sei es durch Zeitgewinn bis zur Erholung des Myokards oder zum Organangebot auf der HTx-Warteliste. Durch den Zeitgewinn, den die VAD`s den zur HTx gelisteten Kindern bieten, brauchen zur Transplantation freigegebene Kinderherzen seltener verworfen werden, mehr Kinder können überleben und die Ausnutzung der angebotenen Organe gelingt besser. / This scientific work addresses the following questions: what is the state of the art in mechanical circulatory support (MCS) in infants and children? How do the different techniques differ? How does mechanical circulatory support influence the systemic inflammatory response after cardiac surgery? What are the indications for use of the pneumatic pulsatile ventricular support system Berlin Heart in children and what do our experience and the results of its use show? The MCS systems most often used for children of all ages are cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), centrifugal pumps and the pneumatic pulsatile ventricular assist device (VAD). These systems vary in indications, results, side effects and potential supporting time. CPB is used to replace the circulation during cardiac surgery. ECMO has been used in our hospital since 1990 for circulatory support in cases of cardiac failure and of pulmonary failure and has been applied in more than 70 children over a period of 1 to 3 weeks. The VAD (Berlin Heart) has been used since 1990 in 56 children for long-term support, when the heart function had to be supported for up to several months. In VAD use there are multiple differences in indication, physiology, underlying disease, technique, anticoagulation and complications between infants, children and adults. In every case of MCS there is contact and complement activation as a reaction of the blood to foreign surfaces, resulting in capillary leak and activation of coagulation and anticoagulation systems with the risk of thrombosis or bleeding. In particular, young infants are prone to systemic inflammatory response in the form of capillary leak. In a prospective study we compared the complement activation after cardiac operations with or without CPB in 35 infants and measured serially the complement function and concentrations or activity of C1q, C3, C4, C1 esterase inhibitor, factor B, the activated split product C3a, prekallikrein and factor XIIa of the contact system. We found that complement activation occurs in all infants but is significantly higher in the group with CPB. Contact activation occurred only in patients who undergo CPB. Thus, the inflammatory response is caused by the use of a CPB circuit and to a lesser degree by surgical procedures and anesthesia. In 27 infants with CPB surgery we prospectively investigated the early clinical parameters that predict the development of capillary leak syndrome (CLS) and examined the relationship between CLS and complement and contact activation and C1 esterase inhibitor during and after bypass. We found that contact and complement activation occurs during CPB and contributes to CLS more frequently in infants of a younger age and with a prolonged bypass time. This activation and decrease in C1 esterase inhibitor was strongly expressed in the CLS group. Although MCS in intractable heart failure in children has normally been limited to centrifugal pumps and ECMO, we implanted 28 children with the pediatric sized pulsatile air-driven Berlin Heart VAD. Our aim was to keep the children alive and allow recovery from shock sequeale until later transplantation or myocardial recovery. Twelve children were brought to the operating room under cardiac massage. In total 12 children died on the system, but thirteen children were transplanted and three were sucessfully weaned from the system. Acute myocarditis appears to be a promising precondition for complete recovery during VAD support and in patients with cardiomyopathy support until transplantation is the goal for the future. We reviewed the course of 95 children who had undergone heart transplantation in our center to investigate whether previous VAD support has an impact on long-term outcome after transplantation. Three groups were compared and we found that bridging to transplantation with a pulsatile pneumatic VAD is a safe procedure in pediatric patients. After transplantation the overall survival rate is 86 % at 1 month, 82 % at 1 year and 75 % at 5 years. The survival of children previously supported with a VAD is similar to that of patients who were bridged with inotropes or who awaited heart transplantation electively. In 4 children with fulminant myocarditis and cardiogenic shock in whom all aggressive medical treatment failed we found that artificial replacement of the heart with complete unloading was followed by total recovery; 3 patients were successfully weaned from the device. No patient died and heart transplantation was necessary in only one child. Retrospectively we examined the course of 84 children who were treated at the ICU, presenting severe cardiac failure due to cardiomyopathy. In 15 of them medical treatment failed and the disease progressed so rapidly that they would have died during the waiting period before a suitable donor organ was found. After resuscitation these 15 children were supported with a VAD. Only 3 died during the waiting period and 12 (80%) underwent later heart transplantation. Progress has been rapid towards individualized choice of mechanical circulatory support systems for children of different ages and with different indications. With the Berlin Heart VAD prolonged circulatory support until myocardial recovery or until heart transplantation is effective in children and infants. It offers time to restore organ function, allows extubation, mobilization and neurological examination and increases the chances for successful transplantation. It can be used with low device-related morbidity and satisfactory results especially in the myocarditis and the cardiomyopathy groups. Complete recovery from secondary organ dysfunction should be achieved before heart transplantation is considered. We expect not only that children with end-stage heart failure will benefit from long-term VAD support, but also that fewer organs from young donors will be lost. Of particular importance is our experience with myocardial recovery in children with acute myocarditis in whom the devices could be explanted.

Patients with terminal heart failure that cannot be treated with conventional therapies are indicated for heart transplantation. In acute deterioration, patients can be brought to transplant using a mechanical cardiac support that is able to partially or completely take over the role of the heart and allow the restoration of sufficient cardiac output (Fila et al., 2014). The period before and after transplantation represents a very challenging period for patients, when they feel not only physical, but especially mental and social needs, which change during their phases of life and at the same time affect their entire subsequent experience. The main goal of this diploma thesis was to monitor how the previous implantation of long-term mechanical cardiac support and the subsequent heart transplantation affect the needs and feelings of patients. Respondents were selected from patients who had been implanted with mechanical cardiac support prior to heart transplantation. The diploma thesis contained another five sub- objectives, which dealt with mapping the needs of patients before and after implantation of long- term mechanical cardiac support and after heart transplantation, as well as during compliance with regimen measures, information retrieval and education. For qualitative research, the method of...

Purpose of Review: To review the clinical evidence on the use of percutaneous coronary intervention (PCI) revascularization options in left main (LM) disease in comparison with coronary artery bypass graft (CABG). Coronary artery disease (CAD) involving the LM is associated with high morbidity and mortality. Though CABG remains the gold standard for complex CAD involving the LM artery, recent trials have shown a trend towards non-inferiority of the LM PCI when compared with CABG in certain subset of patients. Recent Findings: Two recent major randomized trials compared the outcomes of PCI versus CABG in the LM and multi-vessel disease with LM involvement. The NOBLE trial included patients with all range of Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) scores and utilized biolimus drug-eluting stent (DES). The trial concluded that MACCE (major adverse cardiac and cerebrovascular event) was significantly higher with PCI (28%) when compared with CABG (18%) but overall stroke and motility were not different. EXCEL trial evaluated the same treatment option in low to intermediate SYNTAX score population with third-generation everolimus DES platform as PCI option. Results showed no significant differences in the composite primary endpoints of death, stroke, and myocardial infarction (MI) at the end of 30 days (22% versus 19.2%, p = 0.13), although repeat revascularization was higher in PCI group (16.9% versus 10%). Summary: Recent evidence suggests that PCI is an acceptable alternative to treat symptomatic LM stenosis in select group of patients. In low to medium SYNTAX score, particularly in patients without diabetes mellitus, PCI remains a viable option. Future trials focusing on evaluating subset of patients who would benefit from one particular revascularization option in comparison with other is warranted.

L'utilisation d'Assistance Circulatoire Mécanique (ACM) augmente dans le cas d'insuffisance cardiaque terminale ne répondant pas aux traitements médicaux. Dans ce contexte nous avons: 1) présenté une vue d'ensemble des problématiques cliniques, 2) élaboré une nouvelle approche de planification assistée par ordinateur pour l'implantation d'ACM, 3) implémenté un modèle CFD pour comprendre l'hémodynamique ventriculaire induite par la canule apicale. Afin de diminuer les complications, des critères quantitatifs optimisant la décharge ventriculaire pourraient être déterminés par CFD. La planification fournirait des informations permettant de choisir le dispositif et adapter la stratégie clinique. / Mechanical Circulatory Support (MCS) therapy is increasingly considered for patients with advanced heart failure unresponsive to optimal medical treatments. In this context, we: 1) presented an overview of clinical issues raised by MCS implantation, 2) designed a novel computer-assisted approach for planning the implantation, 3) implemented a CFD model to understand the ventricle hemodynamics induced by the inflow cannula pose. With the aim of decreasing complications and morbidity, quantitative criteria for optimizing ventricle unloading could be determined through CFD, and the planning approach may provide valuable information for choosing the device and adapting the clinical strategy.

L’insuffisance cardiaque aigue est une émergence médicale qui nécessite une prise en charge multidisciplinaire. L’Extracorporeal Life Support (ECLS) peut être envisagé comme option thérapeutique pour les formes d’insuffisance cardiaque aigue réfractaire au traitement conventionnel. L’objectif de ce projet de recherche clinique est de fournir une vue d’ensemble de l’ECLS dans la prise en charge du choc cardiogénique et de l’arrêt cardiaque réfractaire. L’intoxication médicamenteuse et la myocardite sont les meilleures indications à l’implantation de l’ECLS en considération de leur potentiel de récupération myocardique très élevé. La défaillance primaire du greffon après transplantation cardiaque et l’infarctus du myocarde présentent des résultats plus mitigés avec l’ECLS en raison d’une physiopathologie plus complexe. Le choc cardiogénique postcardiotomie après une intervention de chirurgie cardiaque montre des résultats décevants en raison du profile préopératoire des patients. L’arrêt cardiaque aussi exige une prise en charge immédiate et l’ECLS peut être considéré comme une solution thérapeutique de sauvetage. Une meilleure sélection des patients s’impose afin d’améliorer les résultats de l’ECLS pour l’arrêt cardiaque réfractaire intrahospitalier. Les résultats de l’ECLS pour l’arrêt cardiaque réfractaire extrahospitalier sont dictés principalement par le temps de réanimation cardio-pulmonaire et le rythme cardiaque. Les rythmes non choquables pourraient être considérés comme une contre-indication formelle à l’utilisation de l’ECLS autorisant une concentration de nos efforts sur les rythmes choquables où les chances de survie sont plus importantes / Acute heart failure is a clinical situation requiring a prompt multidisciplinary approach. Extracorporeal Life Support (ECLS) could represent a therapeutic option for acute heart failure refractory to standard maximal treatment. The aim of this report is to offer an overview of ECLS in the management of refractory cardiogenic shock and cardiac arrest. Drug intoxication and myocarditis are the best indications of ECLS in consideration of their high potential of myocardial recovery. Primary graft dysfunction after heart transplantation and acute myocardial infarction show reduced survival rates owing to their more complex pathophysiology. Postcardiotomy cardiogenic shock after cardiac surgery operations displays poor outcomes due to the preoperative profile of the patients. ECLS could be also considered as a rescue solution for refractory cardiac arrest. A better selection of in-hospital cardiac arrest patients is mandatory to improve ECLS outcomes. In-hospital cardiac arrest patients with a reversible cause like drug intoxication and acute coronary syndrome should benefit from ECLS whereas end-stage cardiomyopathy and postcardiotomy patients with an unclear cause of cardiac arrest should be contraindicated to avoid futile support. ECLS for refractory out-ofhospital cardiac arrest should be limited in consideration of its poor, especially neurological, outcome and the results are mainly limited by the low-flow duration and cardiac rhythm. Nonshockable rhythms could be considered as a formal contraindication to ECLS for refractory out-of-hospital cardiac arrest allowing a concentration of our efforts on the shockable rhythms, where the chances of success are substantial