Home discharge and out-of-hospital follow-up of total artificial heart patients supported by a portable driver system.

To enhance ambulation and facilitate hospital discharge of total artificial heart (TAH)-supported patients, we adapted a mobile ventricular assistance device (VAD) driver (Excor) for TAH use and report on the performance of Excor-driven TAH patients discharged home. Ten patients stabilized on a TAH, driven by the CSS ("Circulatory Support System"), were progressively switched over to the Excor in hospital over 14 days as a pilot, with daily hemodynamics and laboratory parameters measured. Twenty-two stable TAH patients were subsequently placed on the Excor, trained, and discharged home. Clinical and hemodynamic parameters were followed. All pilot study patients were clinically stable on the Excor, with no decrease in TAH output noted (6.3 + 0.3 L/min [day 1] vs. 5.8 + 0.2 L/min [day 14], p = 0.174), with a trend suggesting improvement of both hepatic and renal function. Twenty-two TAH patients were subsequently successfully discharged home on the portable driver and were supported out of hospital for up to 598 days (range, 2-598; mean = 179 ± 140 days), remaining ambulatory, New York Heart Association (NYHA) class I or II, and free of readmission for 88.5% of the time of support. TAH patients may be effectively and safely supported by a mobile drive system. As such, the utility of the TAH may be extended to support patients beyond the hospital, at home, with overall ambulatory freedom.

Results of the European clinical trial of Arrow CorAide left ventricular assist system.

The aim of this study was to evaluate the safety and performance of the Arrow CorAide left ventricular assist system (LVAS) (Arrow International, Reading, PA, USA), a continuous-flow left ventricular assist device, as bridge to transplantation or recovery as well as destination therapy in patients with New York Heart Association (NYHA) class IV heart failure. Twenty-one patients were implanted with the CorAide LVAS between February 2005 and February 2006 in a prospective, multicenter, nonrandomized trial. Seventeen patients (81%) survived to >180 days or to transplantation. The cumulative time on device was 16.58 patient years (range 23-796 days, median 192 days). No intraoperative technical issues were observed at the time of implantation. Of the 21 implants, nine patients died on device, two were converted to other devices, and 10 were transplanted. Three patient deaths were attributed to pump polymer coating delamination. Postmortem device inspection determined delamination of the polymer coating on the pump's internal surface to be the cause of the late hemolysis and sudden fatal pump stops. No embolic or driveline infection event was recorded. The automatic flow control algorithm functioned reliably throughout the trial. Primary performance trial endpoint was achieved with 81% survival to 180 days or transplantation. Delamination of the polymer coating on the internal surface of the pump with resultant hemolysis and pump stops was the sole major device event in this trial. Elimination of the polymer coating and replacement with an amorphous carbon coating has resolved this in preclinical testing, prior to initiation of further clinical testing of this device.

The Thoratec system implanted as a modified total artificial heart: the Bad Oeynhausen technique.

The CardioWest™ total artificial heart (SynCardia Systems, Tuscon, AZ, USA) is the only FDA-approved total artificial heart determined as a bridge to human heart transplantation for patients dying of biventricular heart failure. Implantation provides immediate hemodynamic restoration and clinical stabilization, leading to end-organ recovery and thus eventually allowing cardiac transplantation. Occasionally, implantation of a total artificial heart is not feasible for anatomical reasons. For this patient group, we have developed an alternative technique using the paracorporeal Thoratec biventricular support system (Thoratec, Pleasanton, CA, USA) as a modified total artificial heart. A detailed description of the implantation technique is presented.

Suicide after ventricular assist device implantation.

Depression and anxiety are well documented in patients with end-stage heart failure and correlate with a higher risk of suicide. We report a 69-year-old depressed patient who committed suicide by disconnecting the driveline of his left ventricular assist device almost 3 years after implantation. We provide the medical, psychologic, and psychiatric background of this unique case. This report highlights the importance of pre-implant psychologic screening, the need for regular and long-term psychologic support for this vulnerable patient population, and the need for more qualitative research on patients' views on living with a left ventricular assist device, together with research exploring risk profiles for depression and suicide.

DuraHeart magnetically levitated centrifugal left ventricular assist system for advanced heart failure patients.

The implantable left ventricular assist system (LVAS) using pulsatile pump technology has become an established therapeutic option for advanced heart failure patients. However, there have been technological limitations in some older designs, including a high incidence of infection and mechanical failures associated with moving parts, and the large size of both implantable pump and percutaneous cable. A smaller rotary blood pump emerged as a possible alternative to a large pulsatile pump to overcome some of these limitations. The technological advancement that defines the third-generation LVAS was the elimination of all mechanical contacts between the impeller and the drive mechanism. The DuraHeart LVAS is the world's first third-generation implantable LVAS to obtain market approval (CE-mark), which combines a centrifugal pump and active magnetic levitation. The initial clinical experience with the DuraHeart LVAS in Europe demonstrated that it provided significantly improved survival (85% at 6 months and 79% at 1 year), reduced adverse event rates and long-term device reliability (freedom from device replacement at 2 years: 96 +/- 3%) over pulsatile LVAS.

European experience of DuraHeart magnetically levitated centrifugal left ventricular assist system.

OBJECTIVE: The DuraHeart (Terumo Heart, Inc., Ann Arbor, Michigan, USA) is the world's first approved magnetically levitated centrifugal left ventricular assist system designed for long-term circulatory support. We report the clinical outcomes of 68 patients implanted with the DuraHeart as a bridge to cardiac transplantation in Europe. METHODS: Sixty-eight patients with advanced heart failure (six females), who were eligible for cardiac transplantation were implanted with the DuraHeart between January 2004 and July 2008. Median age was 58 (range: 29-74) years with 31% over 65 years. Thirty-three of these patients received the device as a part of the European multi-center clinical trial. Survival analyses were conducted for 68 patients and other safety and performance data were analyzed based on 33 trial patients. RESULTS: Mean support duration was 242+/-243 days (range: 19-1148, median: 161) with a cumulative duration of 45 years. Thirty-five patients (51%) remain ongoing, 18 transplanted, 1 explanted, and 14 died during support with a median time to death of 62 days. The Kaplan-Meier survival rate during support was 81% at 6 months and 77% at 1 year. Of the 13 patients (21%) supported for >1 year, 4 supported for >2 years, 1 supported >3 years, 2 transplanted, 2 died, and 9 ongoing with a mean duration of 744+/-216 days (range: 537-1148, median: 651). Major adverse events included driveline/pocket infection, stroke, bleeding, and right heart failure. There was no incidence of pump mechanical failure, pump thrombosis, or hemolysis. CONCLUSIONS: The DuraHeart was able to provide safe and reliable long-term circulatory support with an improved survival and an acceptable adverse event rate in advanced heart failure patients who were eligible for transplantation.

Thoratec left ventricular assist device removal after toxic myocarditis.

The clinical manifestation and natural history of myocarditis range is variable from asymptomatic stages to intractable circulatory compromise and death. Supportive therapy is paramount in the treatment of this condition. The use of mechanical circulatory support as bridge-to-recovery or bridge-to-transplantation in cases of cardiovascular collapse is often the only therapeutic option for these patients. We report the case of an adolescent boy with toxic myocarditis, due to cannabis abuse, who was supported with a Thoratec left ventricular assist device (Thoratec Laboratories Corp, Pleasanton, CA) for 96 days before device removal.

Prolonged transcutaneous cardiopulmonary support for postcardiotomy cardiogenic shock.

Percutaneous cardiopulmonary support can be set up quickly at the bedside and provides reliable temporary mechanical circulatory support for cardiogenic shock patients. This report includes the case of a woman, age 56 years, with postoperative cardiogenic shock due to right heart failure, secondary to severe pulmonary hypertension, after mitral and tricuspid valve replacement. This was accomplished by the use of femoro-femoral Levitronix Centrimag centrifugal pump with membrane oxygenator. Adequate cardiac function returned, and the patient could be successively weaned after 37 days of support. Nitric oxide (NO) and Epoprostenol inhalation were used to enhance weaning from cardiopulmonary support. The patient recovered with ambulatory status and acceptable cardiac performance. The patient died of septicemia on postoperative day 72. In conclusion, this case report describes the safety and reliability of the Levitronix Centrimag centrifugal pump as percutaneous cardiopulmonary support for cardiogenic shock.

Total artificial heart-implantation technique using the CardioWest or the Thoratec system.

Total artificial heart is a safe and efficient bridge for patients with terminal congestive heart failure awaiting cardiac transplantation. The implantation of the CardioWest total artificial heart has become an accepted therapeutic option in critically ill patients who have irreversible biventricular failure and are candidates for cardiac transplantation. Because of anatomical limitations in smaller patients (women, adolescents) implantation of the CardioWest system might be impossible. In these cases we have implanted the paracorporeal Thoratec device in a modified technique as a total artificial heart.

Selective upregulation of beta1-adrenergic receptors and dephosphorylation of troponin I in end-stage heart failure patients supported by ventricular assist devices.

In terminal failing hearts, adrenergic receptors are downregulated and intracellular adrenergic signal transduction is inhibited. Mechanical circulatory support by ventricular assist devices (VAD) is used to bridge patients to heart transplantation. Mechanical unloading by VAD may induce reverse remodeling in heart transplantation (HTx) candidates. However, little is known on beta-adrenergic receptor subtype regulation and adrenergic signal transduction under VAD-support. We investigated paired myocardial samples from 16 VAD-supported patients and 9 non-failing donor hearts. We analyzed beta-adrenergic receptor subtype regulation by real-time PCR and radioligand binding and cardiac troponin I phosphorylation (by phospho-cTnI-specific antibodies). We found that the beta1-adrenergic receptor (beta1AR) is downregulated at VAD-implantation on mRNA and protein levels whereas the beta2-adrenergic receptor (beta2AR) was not. After VAD-support, beta1AR protein but not its mRNA was upregulated, whereas the degree of cTnI-phosphorylation was reduced. Upregulation of beta1AR was enhanced by beta blocking medication during VAD-support. However, in 9 out of 15 patients, beta1AR-density remained below the 0.25 percentile of donor hearts. VAD-support is associated with partial normalization of the betaAR-signal transduction pathways. This beneficial effect is related to a posttranscriptional increase in beta1AR-density.

Heparin-induced thrombocytopenia in patients receiving mechanical circulatory support.

OBJECTIVES: Patients receiving mechanical circulatory support are at risk for the development of heparin-induced thrombocytopenia due to the prolonged postoperative use of heparin. We evaluated their antibody status and outcome. METHODS: Between 2003 and 2004, 115 patients received mechanical circulatory support for more than 5 days. Blood samples from postoperative day 7 were retrospectively analyzed for anti-platelet factor 4/heparin antibodies and heparin-induced platelet activation. RESULTS: Overall, 12 (10.6%) patients had heparin-induced thrombocytopenia as defined by in vitro platelet activation, 28 (24.8%) had nonactivating antibodies, and 73 (64.6%) were classified as negative for antibodies. Patients positive for heparin-induced thrombocytopenia had the highest levels of anti-platelet factor 4/heparin immunoglobulin G antibodies. Freedom from thromboembolism was 33%, 33%, and 16% at 1, 3, and 6 months for positive patients, 77%, 68%, and 55% for negative patients (P < .001), and 70%, 53%, and 53% for patients with nonactivating antibodies (P = .068), respectively. The relative risk for thromboembolism in antibody positive patients peaked in the first month of support (odds ratio 7.46, P = .002). Independent risk factors for thromboembolic events included higher anti-platelet factor 4/heparin antibody titers, female gender, and higher fibrinogen levels. CONCLUSION: Heparin-induced thrombocytopenia was more prevalent in patients receiving mechanical circulatory support than in other cardiac patients. Frequent antibody screening is recommended due to the increased risk of thromboembolism. Heparin alternatives should be subjected to clinical trials in these high-risk patients.

Acute fulminant myocarditis in children and adolescents: the role of mechanical circulatory assist.

We report children and adolescents in fulminant myocarditis undergoing prolonged circulatory support with different assist devices. Between 1994 and 2004, seven children and adolescents (aged 7-18 years, mean age 13.5 years) were treated with VADs (5 Thoratec, 1 Medos, 1 Novacor) for circulatory support. Three patients underwent left ventricular support; biventricular support was necessary in four patients. Four patients (three left VADs, one bi-VAD) could be successfully bridged to heart transplantation after a mean support time of 163 days (56-258 days). One 7-year-old girl (Medos-BVAD) died after a support time of 11 days because of irreversible multiorgan failure. One 18-year-old patient was successfully weaned from Thoratec BVAD after 66 days with complete recovery of left ventricular function. As good markers, atrial and brain natriuretic peptides were found which reached normal values after recovery of myocardial function. A 15-year-old girl is still on the device. In children or adolescents with irreversible shock in fulminant myocarditis with an anticipated mortality of 100%, both successful bridging to heart transplantation and successful bridging to recovery are possible. Young patients with fulminant myocarditis should be rapidly transferred to a clinic with a mechanical circulatory support program to offer this life-saving option.

Permanent use of a ventricle assist device for dilated cardiomyopathy in Friedreich's ataxia.

A patient with Friedreich's ataxia was hospitalized due to dilated cardiomyopathy and heart failure. We received informed consent from the patient and his family for implantation of an implantable ventricular assist device (VAD) as permanent support. At the one-year follow-up examination, the neuromuscular symptoms had progressed no further, and he had no VAD systemic failure and complications. This is the first case report of VAD implantation in a Friedreich's ataxia patient.

Triple bridge-to-transplant in a case of giant cell myocarditis complicated by human leukocyte antigen sensitization and heparin-induced thrombocytopenia type II.

Bridge-to-bridge experience has documented the feasibility of a switch from short-term to long-term mechanical circulatory support until heart transplant. We describe a case of irreversible cardiogenic shock due to giant cell myocarditis treated consecutively with extracorporal membrane oxygenation, bi-ventricular assist device, and total artificial heart. The postoperative course was complicated by human leukocyte antigen sensitization and heparin-induced thrombocytopenia type II. Our patient successfully underwent heart transplant after 10 months of support and was discharged in good condition. This case illustrates suitable device selection for myocarditis and represents two treatable immunological complications.

Influence of ACE-inhibition and mechanical unloading on the regulation of extracellular matrix proteins in the myocardium of heart transplantation candidates bridged by ventricular assist devices.

BACKGROUND: Whether adverse structural changes in the myocardium due to remodelling can be reversed by ventricular assist device (VAD) support in patients with end-stage heart failure is controversial. AIMS: To investigate the effect of VAD support on the extra-cellular matrix. METHODS: We analysed the collagen content in terminal failing ventricles of VAD-patients and donor hearts using 4-hydroxyproline for total collagen and real time RT-PCR for fibronectin (FN), collagen I alpha 1 (Col1A1), III alpha 1 (Col3A1) and TGF beta 1 analysis. RESULTS: Compared to donor hearts we found similar increases in Col1A1 and TGF beta1 but not Col3A1 and FN mRNAs, which were similar in the myocardium from patients receiving a VAD or heart transplant. However, patients receiving ACE-I during VAD-support had lower Col1A1 mRNA content at transplantation. The total collagen content was not influenced by mechanical unloading or by ACE-I medication. CONCLUSION: Mechanical unloading by VAD does not reduce the collagen content of the terminal failing ventricle possibly due to increased TGF beta1 levels. However, Col1A1 production may be reduced by ACE-I medication during VAD support.

Mechanical ventricular circulatory support in children; Bad Oeynhausen experience.

INTRODUCTION: Recently various mechanical circulatory support systems are being used all over the world, nevertheless the size of the devices limits the implantation in pediatric cases. Accordingly we report our experiences with assist devices applied for pediatric patients. PATIENTS AND METHODS: Twenty-nine children underwent mechanical circulatory support implantation operation. The diagnoses of preoperation were dilated cardiomyopathy in 16, congenital heart disease in 12 and allograft dysfunction in 1. RESULTS: From November 1987 to January 2004 we implanted 7 LVAD, 11 BVAD and 11 ECMO in pediatric patients. The 29 patients were supported from 11 to 231 days (mean 32.3 days). Three children were supported by Thoratec LVAD. Biventricular Thoratec VAD was used in 3 children. Three children were supported by Medos-HIA system LVAD, and 8 children by biventricular VAD using the Medos-HIA system. One child was supported by Novacor LVAD. Fourteen children were supported by ECMO. We succeeded in heart transplantation in 10 cases, but lost 16 children during the support. Bleeding occurred in 7 cases, thrombosis occurred in 6 cases, infection occurred in 8 cases, pneumothorax occurred in 3 cases and neurological deficit occurred in 2 cases. CONCLUSION: The development of assist device for children which has long durability and small in size as a future subject is desired. Further clinical and experimental research and application of those assist devices for children are in progress.

A multidisciplinary network to save the lives of severe, persistent cardiogenic shock patients.

BACKGROUND: Severe, persistent cardiogenic shock is associated with very high morbidity and lethality. We therefore tried to improve the outcome of these patients using a network between local hospitals and a specialized heart center that has facilities for transplantation and ventricular assist device (VAD) implantation. METHODS: Between 1998 and 2000, 50 patients, who were in cardiogenic shock (mean age 49 years, SD 14) despite high doses of at least three inotropic agents, were admitted to our specialized heart center. During the first 12 hours, we tried to stabilize the patient's condition, to reduce inotropic support agents, and to keep cardiac index above 2.4 L.min(-1).m(-2). According to this strategy, patients were allocated to medical treatment only, emergency VAD therapy, urgent VAD implantation, or heart transplantation. To assess variables potentially influencing patients' outcome, we performed univariate and multivariate analyses. RESULTS: Early in-hospital mortality was 36% and late mortality was 10%. Overall survival at 1, 6, and 12 months of follow-up was 70%, 56%, and 52%, respectively. Even when the heart transplant patients were excluded, overall 12-months survival after cardiogenic shock was still 50%. Higher age, and the absence of sinus rhythm were the only independent risk factors for 12-month mortality. CONCLUSIONS: Our data show that a network between cardiology departments of local hospitals and specialized heart centers can be life-saving for severe, persistent cardiogenic shock patients.

CardioWest total artificial heart: Bad Oeynhausen experience.

BACKGROUND: The use of ventricular assist devices (VAD) has become a widely accepted therapeutic option. However, there are still limitations to the patient collective eligible for VAD placement, who might therefore benefit from the implantation of a total artificial heart. We present the first German single-center experience with the CardioWest total artificial heart (TAH) (SynCardia Systems, Tucson, AZ) in 42 patients. METHODS: Between February 2001 and December 2003, 42 patients (37 men, 5 women, mean age 51 +/- 13 years) received a TAH at our Center. Their body surface area ranged between 1.5 and 2.4 (mean, 1.9 +/- 0.19) m2. All patients were in persistent cardiogenic shock in spite of maximum inotropic support and had numerous preoperative risk factors (intraaortic balloon pumping, mechanical ventilation, acute renal failure, previous cardiac surgery, recent cardiopulmonary resuscitation). RESULTS: Duration of support was 1 to 291 days. Eleven patients (26%) underwent successful transplantation; 9 of them could be discharged home. Twenty-two patients died under support, 21 of them from multiple organ failure and 1 patient from a technical problem. Nine patients are still on the device, 4 of them at home after the original CardioWest console was replaced by the Berlin Heart EXCOR driver (Berlin Heart, Berlin, Germany). Exceptional results were achieved in patients with cardiogenic shock after cardiac surgery or after acute myocardial infarction. CONCLUSIONS: Against the background of the extremely poor preoperative situation of our patients, the overall survival rate of 48% can be considered as favorable. A prospective, randomized study is planned to find out whether patients with idiopathic dilated or ischemic cardiomyopathy are more likely to benefit from a biventricular assist device or a total artificial heart.

The structural examination of myocardial samples from patients with end-stage heart failure supported by ventricular assist devices using electron microscopy and amino acid analysis reveals low degree of reverse remodeling.

BACKGROUND: Chronic heart failure is a multifactorial, progressive disease of many causes and is associated with complex ventricular remodeling. Deposition of extracellular matrix proteins and sarcomeric disarray of the myocytes occur in end-stage heart failure. Ventricular assist devices (VAD), implanted as bridge to transplantation, may reverse ventricular remodeling. Although successfully weaning patients from VAD support has been reported, it is not clear to what degree reversal of remodeling occurs in unloaded failing hearts. Because collagen deposition and ultrastructural disarray are hallmarks of myocardial remodeling, we analyzed the myocardial ultrastructure and collagen content of VAD-supported hearts before and after mechanical unloading. METHODS: We used amino acid analysis to measure collagen content (4-hydroxyproline content) in 24 transplant candidates receiving VAD support. We used transmission electron microscopy to examine the ultrastructure in 6 patients receiving VAD support. RESULTS: The 4-hydroxyproline content increased significantly at VAD implantation and was not altered by mechanical unloading. The ultrastructure showed signs of persisting cardiomyopathy. CONCLUSION: Mechanical unloading does not alter the total collagen content of the supported, failing heart. Thus, structural reversal of the remodeling process associated with heart failure is not a general phenomenon in mechanically unloaded hearts.

Differential regulation of Ca2+-dependent ATPase-activity in left ventricular myocardium during mechanical circulatory support.

BACKGROUND: Myocardial recovery is observed in some end-stage heart failure patients after mechanical circulatory support. The sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase (Ca2+-ATPase) activity is down-regulated in failing myocardium and contributes to heart failure-associated contraction/relaxation abnormalities. Regulation of Ca(2+)-ATPase after mechanical support was shown to be heterogeneous. Thus, we analyzed Ca(2+)-ATPase activity and protein expression in the paired myocardial samples of 21 patients supported by ventricular assist devices to identify factors that influence restoration of the Ca(2+)-transient after ventricular assist device support. METHODS: We measured Ca(2+)-ATPase activity using a reduced nicotinamide-adenine dinucleotide-coupled reaction, determined sarcoplasmic reticulum Ca(2+)-dependent ATPase protein using Western blotting, and determined 4-hydroxyproline using amino-acid analysis. RESULTS: The mean Ca(2+)-ATPase activity decreased at assist-device implantation and slightly increased at transplantation, but remained significantly lower than in non-failing donor hearts. However, individual responses were heterogeneous. Patients with older age, increased left ventricular diameter, and increased 4-hydroxyproline content showed down-regulation of Ca(2+)-ATPase activity, whereas we found up-regulation in patients with low values for these parameters after assist-device support. CONCLUSIONS: Sarcoplasmic reticulum Ca(2+)-ATPase activity, which influences the myocardial Ca(2+)-transient, generally is not restored to normal values in assist-device-supported hearts, but depends on a combined score of the left ventricular end-diastolic diameter, degree of ventricular fibrosis, and age of the patient at the time of assist-device implantation.