Vitamin D metabolites and fibroblast growth factor-23 in patients with left ventricular assist device implants: association with stroke and mortality risk.

PURPOSE: Stroke and mortality risk in patients with left ventricular assist device (LVAD) implants continue to be high. Whether nonclassical cardiovascular risk markers such as vitamin D metabolites and fibroblast growth factor (FGF)-23 contribute to this risk remains to be studied, and this was the objective of our work. METHODS: In 154 LVAD patients (91 HeartWare and 63 HeartMate II implants), we measured circulating 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), parathyroid hormone (PTH) and FGF-23 shortly before LVAD implantation and investigated their association with stroke and mortality risk during 1-year follow-up. RESULTS: Of the study cohort, 34.4 and 92.2%, respectively, had deficient 25OHD (<25 nmol/l) and 1,25(OH)2D3 (<41 pmol/l) values, whereas 42.6 and 98.7%, respectively, had elevated PTH levels (>6.7 pmol/l) and FGF-23 values above the reference range (100 RU/ml). One-year freedom from stroke was 80.9 %, and 1-year survival was 64.3%. The multivariable-adjusted hazard ratio of stroke was 2.44 (95% CI: 1.09-5.45; P = 0.03) for the subgroup of 25OHD levels <25 nmol/l (reference group: 25OHD levels ≥25 nmol/l). The multivariable-adjusted hazard ratio of 1-year mortality was 2.78 (95% CI: 1.52-5.09; P = 0.001) for patients with 25OHD levels <25 nmol/l compared with patients with 25OHD levels ≥25 nmol/l. PTH, FGF-23 and 1,25(OH)2D3 were not associated with stroke or mortality risk. CONCLUSIONS: In LVAD patients, deficient 25OHD levels are independently associated with high stroke and mortality risk. If confirmed in randomized controlled trials, preoperative correction of deficient vitamin D status could be a promising measure to reduce stroke and mortality risk in LVAD patients.

[Heart and combined heart-lung transplantation. Indications, chances and risks]. / Herz- und Herz-Lungen-Transplantation. Indikationen, Chancen, Risiken.

Orthotopic heart transplantation (HTX) is nowadays the worldwide accepted gold standard for the treatment of terminal heart failure. The main indications for HTX are non-ischemic dilatative (54%) and ischemic (37%) heart failure. In the acute phase after HTX the survival rate is approximately 90%. Good short and long-term results with survival rates ranging from 81% after 1 year to more than 50% after 11 years demonstrate that there is currently no real treatment alternative to HTX for treatment of end-stage heart failure. In the case of irreversible pulmonary hypertension in combination with end-stage heart failure or complex congenital heart syndromes, a combined heart and lung transplantation (HLTX) is necessary. Compared with HTX the short-term survival of HLTX is reduced, mostly for technical reasons. Improved long-term results after HTX and HLTX are a result of highly specialized transplantation units and effective immunosuppression. However, a major problem is the shortage of organ donors in Germany and the resulting long waiting times for patients with frequently occurring blood groups of up to 10 months for transplantation. The consequence of the latter is the ever increasing number of implanted cardiac assist devices in patients not only as a bridge to transplant but also as destination therapy.

[Reconstructive surgery in patients with a ventricular assist device (VAD)--an interdisciplinary challenge]. / Rekonstruktive Chirurgie bei Patienten mit Herzunterstützungssytemen (Ventricular Assist Device, VAD)--eine interdisziplinäre Herausforderung.

BACKGROUND: Ventricular assist devices (VAD) are implanted with a growing frequency in patients with end-stage heart failure. In spite of technical and therapeutic advances, there is still a high incidence of device infections and healing disturbances with a considerable mortality. Reconstructive plastic surgery is able to provide help in erradicating infections and covering defects. PATIENTS AND METHODS: 11 patients with device infections and soft tissue defects were treated in our institution. All cases were treated with local myocutaneous or muscle flaps. RESULTS: Three patients had postoperative haematomas which had to be revised surgically. One patient had a persistent fistula of mediastinal origin but without clinical symptoms of infection. One patient exhibited an enterocutaneous fistula after defect coverage. CONCLUSION: Patients with VADs have a high possibility of perioperative complications. Therefore a close interdisciplinary approach with plastic and cardiovascular surgeons is absolutely essential.

The MiniACcor: constructive redesign of an implantable total artificial heart, initial laboratory testing and further steps.

The Aachen Total Artificial Heart (ACcor) has been under development at the Helmholtz Institute in Aachen over the last decade. It may serve as a bridge to transplant or as a long-term replacement of the natural heart. Based upon previous in vivo experiments with the ACcor total artificial heart, it was decided to optimize and redesign the pump unit. Smaller dimensions, passive filling and separability into three components were the three main design goals. The new design is called the MiniACcor, which is about 20% smaller than its predecessor, and weighs only 470 grams. Also its external driver/control unit was miniaturized and a new microcontroller was selected. To validate the design, it was extensively tested in laboratory mock loops. The MiniACcor was able to pump between 4.5 and 7 l/min at different pump rates against normal physiological pressures. Several requirements for the future compliance chamber and transcutaneous energy transmission (TET) system were also measured in the same mock loop. Further optimization and validation are being performed in cooperation with the Heart and Diabetes Centre North Rhine-Westphalia.

Implantation of CardioWest total artificial heart for irreversible acute myocardial infarction shock.

Patients who develop cardiogenic shock after acute myocardial infarction have a very high mortality rate despite early reperfusion therapy. Hemodynamic stabilization can often only be achieved by implanting a mechanical circulatory support system. When, in cases representing expansive myocardial impairment without any chance of recovery, pharmacological therapy and the use of percutaneous assist devices have failed, the implantation of a total artificial heart is indicated. We report our first experiences with this extensive and innovative method of managing irreversible cardiogenic shock patients. The CardioWest total artificial heart was implanted in 5 patients (male; mean age, 50 years). All patients were in irreversible cardiogenic shock despite maximum dosages of catecholamines, an intra-aortic balloon pump and/or a femoro-femoral bypass. In all patients early reperfusion therapy was performed. After implantation of the Cardio West system, all dysfunctional organ systems rapidly recovered in all patients. Four of 5 patients underwent successful heart transplantation after a mean support time of 156 days. One patient died because of enterocolic necroses caused by an embolic event after termination of dicumarol therapy. In summary, our first experiences justify this extensive management in young patients who would otherwise have died within a few hours.

A risk score to predict 30-day mortality in patients with intra-aortic balloon pump implantation.

BACKGROUND: Several risk factors for early mortality after intra-aortic balloon pump (IABP) implantation have been described. METHODS: We performed a retrospective analysis in 120 patients receiving peri- or postoperative IABP support. Univariate and multivariate analyses were carried out to assess variables potentially influencing 30-day mortality in order to develop a risk score for the prognosis of survival and for the decision on optimal patient-specific treatment. RESULTS: The 4 parameters (mean arterial pressure, adrenaline dose, central venous pressure, and blood lactate concentrations) at 6 hours of IABP use were independently related to 30-day mortality. They were used to develop a risk score (0 - 4 points). With this score, patients who scored 3 or 4 points had no probability of surviving, whereas patients with a score of zero had a probability of 84.4 %. A prospectively screened cohort of 145 patients confirmed the reliability of our risk score. CONCLUSIONS: Our data demonstrate that a score can predict 30-day mortality in patients with IABP implantation. Such a score can be useful to find out whether or not ECMO/VAD implantation is necessary.

IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory support.

Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparin-induced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and non-platelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5-7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n = 10), non-platelet-activating anti-PF4/heparin antibodies (n = 53), and anti-PF4/heparin antibody negative (n = 50). Patients with platelet-activating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P = 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate.

[Implantation of CardioWest total artificial heart in irreversible acute myocardial infarction shock-new hope for patients with infaust prognosis]. / Einsatz des CardioWest-Kunstherzens beim irreversiblen kardiogenen Schock nach Myokardinfarkt. Eine Hoffnung für Patienten mit infauster Prognose.

Patients in whom cardiogenic shock develops after acute myocardial infarction have a very high death rate despite early reperfusion therapy. Often hemodynamic stabilization can be achieved only by implantation of a mechanical circulatory support system. When pharmacological therapy and onset of percutaneous assist devices fails in cases representing expansive myocardial impairment without any chance of recovery, the indication for implanting a total artificial heart is given. We report on our first experiences with this extensive and innovative management of irreversible cardiogenic shock patients. In five patients (male, mean age 50 years) the CardioWest total artificial heart was implanted. All patients were in irreversible cardiogenic shock despite maximal dosages of catecholamines, intraaortic balloon pump and/or femorofemoral bypass. In all patients early reperfusion therapy was performed. After implantation of the CardioWest system, rapid recovery of all dysfunctional organ systems occurred in all patients. Four of five patients underwent successful heart transplantation after a mean support time of 156 days. One patient died because of enterocolic necroses caused by embolic event after termination of dicumarol therapy. In summary, first experiences justify this extensive management in these young patients who otherwise would have died within a few hours.

Device and patient management in a bridge-to-transplant setting.

BACKGROUND: A variety of sophisticated devices have been developed for mechanical circulatory support in patients bridged to cardiac transplantation. Based on 13 years' experience, we have developed specific protocols for patient selection and management for different devices. METHODS: The principal systems applied in the bridge-to-transplant cohort are the Thoratec ventricular assist device (n = 144, mean duration of support 53 +/- 57 days), the Novacor left ventricular assist system (LVAS) (n = 85, mean duration of support 154 +/- 15 days), and the HeartMate LVAS (n = 54, mean duration of support 143 +/- 142 days). The Thoratec device is used for biventricular assistance or if the duration of support is expected to be less than 6 months. For long-term support, either the Novacor or HeartMate LVAS are preferred. RESULTS: Despite careful postoperative patient management, this group of patients is prone to a variety of complications. Bleeding occurred in 22% to 35%, right heart failure in 15% to 26%, neurologic disorders in 7% to 28%, infection in 7% to 30%, and liver failure in 11% to 20% of patients. Complications varied with the device applied and the patient's preoperative condition. A total of 73 patients were discharged from hospital for a mean period of 184 days; this cumulative experience amounted to 37.5 patient-years. CONCLUSIONS: The Novacor and the HeartMate systems offer the additional possibility of discharging patients during support if they fulfill certain criteria. The main reasons for rehospitalization were thromboembolic and infectious complications.

Midterm follow-up of patients discharged from hospital under left ventricular assistance.

BACKGROUND: Against the background of increasing demand for long-term mechanical circulatory support, discharging patients to their homes while on assist devices becomes more and more important. This report describes the midterm follow-up of 66 patients who were allowed to leave the hospital under left ventricular assist device (LVAD) support with Novacor or HeartMate systems. Between May 1994 and January 2000, 66 patients (9 women, 57 men, between 15 and 68 years old) under LVAD support fulfilled our criteria for being discharged home on the device. Intent to treat comprised bridging to transplantation in 59 patients, bridging to recovery in 5 patients, and alternative to transplantation in 2 patients. Forty-four patients received support with Novacor, 18 patients with the VE HeartMate, 2 patients with centrifugal pumps and Novacor, and 1 patient each with Novacor and Thoratec/Medos HIA-VAD. The mean out-of-hospital (OOH) follow-up period was 162 +/- 187 days, with a cumulative OOH experience of 30 patient years. Twenty-nine patients were not readmitted, and 37 patients were readmitted 54 times (23 patients were readmitted once, 11 patients twice, and 3 patients 3 times). The primary reasons for readmission included neurologic disorders and infection complications. At 229 days, 50% of all patients were free from readmission. The readmission rate was 1.8 patient/year. Sixteen patients died while on LVAD support (24%). Our midterm follow-up results show the safety and efficacy of this therapeutic option. Acceptable hospital readmission rates strongly support the future use of this technology as an alternative to transplantation in managing end-stage heart failure patients.

Pre-existing elevated pulmonary vascular resistance: long-term hemodynamic follow-up and outcome of recipients after orthotopic heart transplantation.

BACKGROUND: Elevation of pulmonary vascular resistance (PVR) has been considered to predict a bad outcome after orthotopic heart transplantation (HTx). A transpulmonary gradient (TG) > or =15 mmHg and PVR > or =5 wood (w) are correlated with a three-fold increase in 2-days as well as 30-days and 6-, 12-month mortality. METHODS: We performed a retrospective analysis of 400 consecutive transplanted patients (pts) on hemodynamic data over a time period of 3.5 years. In 83 pts (23%) preoperative PVR was > or =5 w and TG >15 mmHg. Vasodilator studies were performed in this group of pts in order to evaluate pulmonary vasoreactivity or hemodynamic improvement. RESULTS: Hemodynamic follow-up post-transplantation showed a significant (p<0.001) decrease in mean TG to 8.8 mmHg within the first, 7.7 after the fifth year as well as decrease in PVR from 5.5 to 1.6, within the first and fifth year post-transplantation. Compared to the control group (n=286) (re-transplants n=6 and pediatric pts n=25 excluded) pts with TG <15 mmHg and/or PVR <5 w, transplanted within the same period, 30-day mortality and cumulative survival after 1 and 5 years do not show any significant difference with a mortality of 3%, 22% and 33% (p<0.05). Subgroup analysis for pts with endstage of ischemic versus dilatative cardiomyopathy has not shown any significant difference in mortality. CONCLUSIONS: In a retrospective analysis of 400 pts elevated PVR does not predict a bad outcome after orthotopic heart transplantation in early and late mortality.

Single-center experience with the thoratec ventricular assist device.

OBJECTIVE: The Thoratec ventricular assist device (Thoratec Laboratories, Pleasanton, Calif) is widely accepted for univentricular and biventricular support in patients with various indications. The aim of this study is to describe our experience with implantation of the Thoratec ventricular assist device in more than 100 patients. METHODS: From March 1992 to June 1998, 114 patients (98 men and 16 women; mean age, 47.9 years) received the Thoratec ventricular assist device for a mean duration of 44.9 days. The patients were divided into 3 groups. Group 1 included 84 patients in whom the system was applied as a bridge-to-transplant procedure. Group 2 included 17 patients with postcardiotomy cardiogenic shock, and group 3 included 13 patients with cardiogenic shock of other causes. RESULTS: Sixty-eight percent of patients in group 1 survived to transplantation with a posttransplant survival of 88%. The only independent risk factor affecting survival was age more than 60 years. Survivals in groups 2 and 3 were 47% and 31%, respectively. Main complications in all groups were bleeding, multiple organ failure, liver failure, sepsis, and neurologic disorders. CONCLUSIONS: The Thoratec ventricular assist device has proved to be a reliable device for bridge to transplantation and postcardiotomy support. Further studies are required on patient selection and on patient and device management to reduce the incidence of complications in these patient populations.

Influence of different assist devices on survival after orthotopic heart transplantation.

BACKGROUND: In 1995, a risk factor of 1.88 was indicated for one-year mortality in connection with bridging to heart transplantation. Both one-year and three-year survival rates in patients bridged to transplantation were less than 80%. METHODS: From 3/89 to 12/98, 903 orthotopic heart transplantations were performed at our center in 888 recipients. Bridging was necessary in 142 patients. RESULTS: The one-year survival rate was 76% in pts without VAD, 86% in pts bridged with VAD and 66% in pts with VAD due to postcardiotomy syndrome. The three-year survival rates were 73%, 80% and 55% respectively. CONCLUSIONS: Early and late results in patients bridged to transplantation remarkably improved over 1995. One-year and long-term survival rates are significantly lower when assist devices are used in patients with postcardiotomy syndrome. Despite a high incidence of assist-related complications, electively bridged patients showed significantly better early and long-term results than the control group.

Bridging to cardiac transplantation with the Thoratec Ventricular Assist Device.

Mechanical circulatory support has become an established procedure for bridging patients to cardiac transplantation. One of the devices available is the Thoratec VAD, which can be applied for univentricular or biventricular support. Between March 1992 and June 1997, 74 patients were bridged with Thoratec VAD to cardiac transplantation. In 67 patients the system was applied exclusively (26 LVAD, 38 BVAD, 3 TAH), in 7 patients subsequently or in combination with another MCS device. 71.6% with exclusive Thoratec application underwent transplantation with a post-transplant survival rate of 90%, 4 patients are still waiting. Transplant rate in LVAD and BVAD patients was 84% and 71.4%, respectively, posttransplant survival 95.2% and 88%, respectively. 28.6% with a combined application of Thoratec and another MCS device survived to be discharged from hospital. Main complications were bleeding, liver failure, multiple organ failure, and infections. In terms of reliability and efficacy the Thoratec VAD is the system of choice for mid-term application in patients bridged to cardiac transplantation.

Development and initial in vivo testing of a new hydraulic drive system (Paedipump) for circulatory support in infants.

The main limitation in the use of circulatory support in children is the lack of an adequate system with regard to size and pumping capacity. Recently, two pneumatically driven ventricular support systems with low volume chambers for use in a pediatric population became available. We have developed a hydraulic drive system with an advantageous exact control of the stroke volume. The system enables two different modes of operation: the full-empty and the filled-empty modes. In both cases the ventricle is empty at the end of systole. This new system was tested in experimental animals (6 pigs, body weight 9.5-14.0 kg) with normal and reduced left ventricular function (MAP<45 mmHg). A 25 ml ventricle (HIA-Medos) was implanted. The full-empty and the filled-empty mode used led to a significant load reduction, both in animals with normal and impaired cardiac function. Plasma lactate levels, pH-values and total body O2-consumption were in the normal range during circulatory support indicating adequate organ perfusion. Results showed that sufficient ventricular support was achieved during all pumping modes due to the possibility of controlling and modifying the stroke volume of the hydraulically driven support system employed according to necessity. This is a promising feature for its future application in infants with congenital or acquired heart diseases.

Extended donor criteria: use of cardiac allografts after carbon monoxide poisoning.

BACKGROUND: An increasing demand for cardiac allografts for the treatment of end-stage cardiac failure has led to a shift in the traditional views about donor criteria. The use of allografts exposed to high concentrations of carbon monoxide is still under discussion. The current literature on this topic is contradictory. We describe our experience with orthotopic cardiac transplantation, using cardiac allografts after carbon monoxide poisoning. METHODS: Between March 13, 1989 and August 1, 1996, 770 orthotopic heart transplantations were performed in our center. Within this period, we accepted five cardiac allografts from brain-dead, carbon monoxide-poisoned donors. Donor history showed carbon monoxide intoxication in all cases. At the time of organ explantation, donor hemodynamic parameters were feeble in all patients. RESULTS: The postoperative course was uneventful in three of the five recipients. The overall 3-year survival rate in this small group is 40%. Induction therapy or rescue therapy with mono/polyclonal antibodies was not necessary. Myocardial right-ventricular biopsies did not show any specific signs of carbon monoxide poisoning. CONCLUSIONS: In our opinion, cardiac allografts from donors exposed to carbon monoxide can be transplanted successfully in infants and adults, if there are no signs of severe hemodynamic dysfunction in the presence of a normal central venous pressure and low-dose support with catecholamines and there are no electrocardiographic changes in combination with elevated transaminase. With extended donor criteria, the hearts of carbon monoxide-poisoned victims could increase the number of suitable organs and lower the death rate of patients on the United Network for Organ Sharing and Eurotransplant International Foundation waiting lists.

Management of acute fulminant myocarditis using circulatory support systems.

Although the natural history of acute myocarditis leads to complete recovery in the majority of patients, rapid and irreversible cardiac decompensation resulting in death is known to occur. One possible therapy to improve the poor prognosis of this patient group may be the implantation of circulatory support systems that allow myocardial recovery or bridging to heart transplantation. Therapeutic protocols have been suggested, but clinical experiences in this area are few. In this paper we report on our clinical experiences in cardiogenic shock after acute fulminant myocarditis using different types of circulatory support systems. Three different systems were used: a biomedicus centrifugal pump as a ventricular assist device (VAD) or femoro-femoral bypass (FFB) including oxygenator; Abiomed BVS 5000, and Thoratec ventricular assist device. Hemodynamic criteria for implantation of support systems were cardiac index < 2.0 L/min/m2. SVR = 1000 dyne-s-cm-5, central venous pressure (CVP) or left atrial pressure (LAP) > 20 mm Hg, and urine output < 20 ml/h despite maximal pharmacological therapy. Age total of 5 patients (mean age 29 years, range 15-55 years) in cardiogenic shock after acute fulminant myocarditis were included. Two patients initially were supported for stabilization and transportation from an outside hospital by FFB. Both patients died after a support time of 24 h because of multiorgan failure or neurological disorders after longer periods of resuscitation in the referral hospital. The third patient (55 years) received the Biomedicus pump as CVAD. Myocardial function recovered after a support time of 120 h, and the patient could be weaned. Unfortunately, 2 days after weaning, he developed malignant arrhythmias and died. The 2 remaining patients (15 years and 27 years) with diagnosis of acute fulminant virus myocarditis were supported by biventricular assist device (1 x Thoratec/111 days, 1 x Abiomed/7 days). During the entire time of support, there were no signs of myocardial recovery. The patients were accepted for the heart transplantation (HTX) program. In both cases, HTXs were performed without any complication. The postoperative course was uneventful. The results of mechanical circulatory support in patients with acute fulminant myocarditis are encouraging and justify the resources.