The Introduction of an MR-Conditional Prototype for Cardiopulmonary Bypass Support: Technical Aspects and System Requirements.

INTRODUCTION: The use of cardiopulmonary bypass (CBP; also known as a heart-lung machine) in newborns with complex congenital heart defects may result in brain damage. Magnetic resonance imaging (MRI) assessments cannot be performed safely because the metal components used to construct CBP devices may elicit adverse effects on patients when they are placed in a magnetic field. Thus, this project aimed to develop a prototype MR-conditional circulatory support system that could be used to perform cerebral perfusion studies in animal models. METHODS: The circulatory support device includes a roller pump with two rollers. The ferromagnetic and most of the metal components of the roller pump were modified or replaced, and the drive was exchanged by an air-pressure motor. All materials used to develop the prototype device were tested in the magnetic field according to the American Society for Testing and Materials (ASTM) Standard F2503-13. The technical performance parameters, including runtime/durability as well as achievable speed and pulsation behavior, were evaluated and compared to standard requirements. The behavior of the prototype device was compared with a commercially available pump. RESULTS: The MRI-conditional pump system produced no image artifacts and could be safely operated in the presence of the magnetic field. The system exhibited minor performance-related differences when compared to a standard CPB pump; feature testing revealed that the prototype meets the requirements (i.e., operability, controllability, and flow range) needed to proceed with the planned animal studies. CONCLUSION: This MR-conditional prototype is suitable to perform an open-heart surgery in an animal model to assess brain perfusion in an MR environment.

Paediatric aortic valve replacement using decellularized allografts.

OBJECTIVES: Options for paediatric aortic valve replacement (AVR) are limited if valve repair is not feasible. Results of paediatric Ross procedures are inferior to adult Ross results, and mechanical AVR imposes constant anticoagulation with the inherent risks. METHODS: The study design was a prospective, multicentre follow-up of all paediatric patients receiving decellularized aortic homografts (DAHs) for AVR in 8 European centres. RESULTS: A total of 106 children (77 boys) were operated (mean age 10.1 ± 4.8 years, DAH diameter 20.5 ± 3.8 mm). A total of 60 (57%) had undergone previous surgical interventions: 34 with 1, 15 with 2 and 11 with ≥3. There was one early death in a 12-year-old girl, who underwent her fourth aortic valve operation, due to intracerebral haemorrhage on extracorporeal membrane oxygenation after coronary reimplantation problems following 3-sinus reconstruction 1 year earlier. One 2-year-old patient died due to sepsis 2 months postoperatively with no evidence for endocarditis. In addition, a single pacemaker implantation was necessary and a 2.5-year-old girl underwent successful HTx due to chronic myocardial failure despite an intact DAH. After a mean follow-up of 3.30 ± 2.45 years, primary efficacy end points mean peak gradient (18.1 ± 20.9 mmHg) and regurgitation (mean 0.61 ± 0.63, grade 0-3) were very good. Freedom from death/explantation/endocarditis/bleeding/stroke at 5 years was 97.8 ± 1.6/85.0 ± 7.4/100/100/100% respectively. Calculated expected adverse events were lower for DAH compared to cryopreserved homograft patients (mean age 8.9 years), lower than in Ross patients (9.4 years) and in the same range as mechanical AVR (12.8 years). CONCLUSIONS: Even though the overall number of paediatric DAH patients and the follow-up time span are still limited, our data suggest that DAHs may present a promising additional option for paediatric AVR.

Antithrombotic therapy in pediatric ventricular assist devices: Multicenter survey of the European EXCOR Pediatric Investigator Group.

OBJECTIVES: Mechanical circulatory support for pediatric heart failure patients with the Berlin Heart EXCOR ventricular assist system is the only approved and established bridging strategy for recovery or heart transplantation. In recent years, the burden of thromboembolic events has led to modifications of the recommended antithrombotic therapy. Therefore, we aimed to assess modifications of antithrombotic practice among the European EXCOR Pediatric Investigator Group members. METHODS: We sent a questionnaire assessing seven aspects of antithrombotic therapy to 18 European hospitals using the EXCOR device for children. Returned questionnaires were analyzed and identified antithrombotic strategies were descriptively compared to "Edmonton protocol" recommendations developed for the US EXCOR pediatric approval study. RESULTS: Analysis of 18 received surveys revealed substantial deviations from the Edmonton protocol, including earlier start of heparin therapy at 6-12 h postoperatively and in 50% of surveyed centers, monitoring of heparin effectiveness with aPTT assay, administering vitamin K antagonists before 12 months of age. About 39% of centers use higher international normalized ratio targets, and platelet inhibition is changed in 56% including the use of clopidogrel instead of dipyridamole. Significant inter-center variability with multiple deviations from the Edmonton protocol was discovered with only one center following the Edmonton protocol completely. CONCLUSION: Current antithrombotic practice among European EXCOR users representing the treatment of more than 600 pediatric patients has changed over time with a trend toward a more aggressive therapy. There is a need for systematic evidence-based evaluation and harmonization of developmentally adjusted antithrombotic management practices in prospective studies toward revised recommendations.

Heart transplantation in congenital heart disease: in whom to consider and when?

Due to impressive improvements in surgical repair options, even patients with complex congenital heart disease (CHD) may survive into adulthood and have a high risk of end-stage heart failure. Thus, the number of patients with CHD needing heart transplantation (HTx) has been increasing in the last decades. This paper summarizes the changing etiology of causes of death in heart failure in CHD. The main reasons, contraindications, and risks of heart transplantation in CHD are discussed and underlined with three case vignettes. Compared to HTx in acquired heart disease, HTx in CHD has an increased risk of perioperative death and rejection. However, outcome of HTx for complex CHD has improved over the past 20 years. Additionally, mechanical support options might decrease the waiting list mortality in the future. The number of patients needing heart-lung transplantation (especially for Eisenmenger's syndrome) has decreased in the last years. Lung transplantation with intracardiac repair of a cardiac defect is another possibility especially for patients with interatrial shunts. Overall, HTx will remain an important treatment option for CHD in the near future.

Reverse graft placement in the Florida sleeve procedure for aortic root aneurysm.

Since August 2009, 22 patients with aortic root aneurysm have been successfully operated on with our new aortic remodeling technique as follows: after placement of the Gelweave (Vascutek, Ltd., Inchinnan, UK) Valsalva vascular graft in the reverse manner to the Florida sleeve procedure, the aortic annulus was fixed with the collar of this prosthesis at the level of the basal ring and the aortic root was wrapped with the prosthesis. Furthermore, the aortic valve commissures were resuspended. The distal end of the graft and the transected aortic wall were sutured together with running sutures when they were anastomosed to the stump of the distal ascending aorta.

Blood transfusion determines postoperative morbidity in pediatric cardiac surgery applying a comprehensive blood-sparing approach.

OBJECTIVE: Recently we suggested a comprehensive blood-sparing approach in pediatric cardiac surgery that resulted in no transfusion in 71 infants (25%), postoperative transfusion only in 68 (24%), and intraoperative transfusion in 149 (52%). We analyzed the effects of transfusion on postoperative morbidity and mortality in the same cohort of patients. METHODS: The effect of transfusion on the length of mechanical ventilation and intensive care unit stay was assessed using Kaplan-Meier curves. To assess whether transfusion independently determined the length of mechanical ventilation and length of intensive care unit stay, a multivariate model was applied. Additionally, in the subgroup of transfused infants, the effect of the applied volume of packed red blood cells was assessed. RESULTS: The median length of mechanical ventilation was 11 hours (interquartile range, 9-18 hours), 33 hours (interquartile range, 18-80 hours), and 93 hours (interquartile range, 34-161 hours) in the no transfusion, postoperative transfusion only, and intraoperative transfusion groups, respectively (P < .00001). The corresponding median lengths of intensive care unit stay were 1 day (interquartile range, 1-2 days), 3.5 days (interquartile range, 2-5 days), and 8 days (interquartile range, 3-9 days; P < .00001). The multivariate hazard ratio for early extubation was 0.24 (95% confidence interval, 0.16-0.35) and 0.37 (95% confidence interval, 0.25-0.55) for the intraoperative transfusion and postoperative transfusion only groups, respectively (P < .00001). In addition, the cardiopulmonary time, body weight, need for reoperation, and hemoglobin during cardiopulmonary bypass affected the length of mechanical ventilation. Similar results were obtained for the length of intensive care unit stay. In the subgroup of transfused infants, the volume of packed red blood cells also independently affected both the length of mechanical ventilation and the length of intensive care unit stay. CONCLUSIONS: The incidence and volume of blood transfusion markedly affects postoperative morbidity in pediatric cardiac surgery. These results, although obtained by retrospective analysis, might stimulate attending physicians to establish stringent blood-sparing approaches in their institutions.

Factors associated with the need of biventricular mechanical circulatory support in children with advanced heart failure.

OBJECTIVES: Postimplantation right ventricular dysfunction is associated with increased morbidity and mortality in ventricular assist device (VAD) recipients. This study aimed to determine the preoperative risk factors for severe right heart failure needing biventricular mechanical circulatory support in children with end-stage heart failure. METHODS: We reviewed data from 84 children supported with long-term VADs at the German Heart Institute Berlin between January 1999 and October 2010. Right ventricular assist device (RVAD) support was needed for 24 (29%) patients, and the other 60 (71%) were implanted with left ventricular assist devices (LVADs). RESULTS: The median age at implantation was 7 years (12 days-18 years), and the median support time was 41 days (1-432 days). Of the 84 patients, the overall survival to transplantation or recovery of ventricular function was 69%. Compared with children implanted with LVAD, patients receiving biventricular support had significantly higher postoperative mortality (P = 0.04). The multivariate logistic regression indicated that decreased milrinone use was the only preoperative factor independently associated with increased requirement for biventricular support (odds ratio: 0.1, 95% confidence interval: 0.04-0.64, P = 0.01). Children treated with milrinone preoperatively showed improved survival after implantation (P = 0.04). CONCLUSIONS: Paediatric patients needing biventricular support had significantly higher postoperative mortality. Preoperative milrinone use might decrease the risk of severe right ventricular failure requiring additional RVAD insertion and improve postimplantation survival in children with advanced heart failure.

Reoperations on the pulmonary autograft and pulmonary homograft after the Ross procedure: An update on the German Dutch Ross Registry.

OBJECTIVES: Reinterventions after the Ross procedure are a concern for patients and treating physicians. The scope of the present report was to provide an update on the reinterventions observed in the large patient population of the German-Dutch Ross Registry. PATIENTS AND METHODS: From 1988 to 2011, 2023 patients (age, 39.05 ± 16.5 years; male patients, 1502; adults, 1642) underwent a Ross procedure in 13 centers. The mean follow-up was 7.1 ± 4.6 years (range, 0-22 years; 13,168 patient-years). RESULTS: In the adult population, 120 autograft reinterventions in 113 patients (1.03%/patient-year) and 76 homograft reinterventions in 67 patients (0.65%/patient-year) and, in the pediatric population, 14 autograft reinterventions in 13 patients (0.91%/patient-year) and 42 homograft reinterventions in 31 patients (2.72%/patient-year) were observed. Of the autograft and homograft reinterventions, 17.9% and 21.2% were performed because of endocarditis, respectively. The subcoronary technique in the adult population resulted in significantly superior autograft durability (freedom from autograft reintervention: 97% at 10 years and 91% at 12 years; P < .001). The root replacement technique without root reinforcement (hazard ratio, 2.4; 95% confidence interval, 1.4-4.1) and the presence of pure aortic insufficiency preoperatively (hazard ratio, 2.3; 95% confidence interval, 1.5-3.5) were statistically significant predictors for a shorter time to reoperation. The center volume had a significant influence on the long-term results. The freedom from homograft reoperation for the adults and pediatric population was 97% and 87% at 5 years and 93% and 79% at 12 years, respectively (P < .001), with younger recipient and donor age being significant predictors of a shorter time to homograft reoperation. CONCLUSIONS: The autograft principle remains a valid option for young patients requiring aortic valve replacement. The risk of reoperation depends largely on the surgical technique used and the preoperative hemodynamics. Center experience and expertise also influence the long-term results. Adequate endocarditis prophylaxis might further reduce the need for reoperation.

Gender differences during mechanical circulatory support.

Long-term mechanical circulatory support (MCS) with ventricular assist devices (VADs) is now an acceptable option for patients with end-stage heart failure (HF). There are growing numbers of reports identifying sex-related differences in the development and prognosis of HF and cardiac surgery. With the experience of 1,607 VAD implantations in our institution we are the first to analyze our data to determine gender distribution in our patient populations and the effect of gender on outcomes. Of the total 1,456 patients with MCS, 1,225 were male and 231 female. The patients were divided into three age groups-below 13 years (group 1, n = 100), between 13 and 50 years (group 2, n = 540) and older than 50 years (group 3, n = 824). Five-year survival, HF etiology, and procedural success, defined as 30-day and 5-year survival were analyzed retrospectively. In group 1 the gender distribution was equal; the leading HF etiology was dilated cardiomyopathy (DCMP) with 17% in male (n = 17) and 19% in female (n = 19) patients, followed by congenital diseases (13% in male versus 9% in female) and postcardiotomy failure (13% in male versus 8% in female). No differences were seen in 5-year survival and procedural success. In group 2, significantly more men (n = 451, p < 0.0001) were supported by VADs. DCMP was the major cause for VAD implantation (54%) and was significantly more frequent in men (57.6%, p = <0.0001). Male patients were older (mean age = 37.1 years, p < 0.0001), with a longer median support time (151.6 days, p < 0.0001) and a higher median weight (78.2 kg, p < 0.0001). No difference was seen in procedural success whereas 5-year survival was better in men than in women (53% vs. 42%, p = 0.02).Group 3 consisted of 723 male patients and 101 female patients (p < 0.0001). Ischemic cardiomyopathy was the main HF etiology (37.9 %) and it was significantly more often the reason for left ventricular assist device support in men (p = 0.009). No differences were seen in procedural success; 5-year survival showed a better outcome in men (49% vs. 25%, p = 0.026). In patients supported by a VAD, gender has a significant impact on the distribution of diagnoses in the adult population. Women were underrepresented in the age group 13-50 years, and 50 years and older, and women had a higher risk for mortality on VAD support in the adult age groups (groups 2 and 3).

Establishment of a coculture model for studying inflammation after pediatric cardiopulmonary bypass: from bench to bedside.

Cardiopulmonary bypass (CPB) has been known to induce an inflammatory response that is influenced by various factors. Hypothermia is supposed to reduce inflammation after CPB. We developed an in vitro coculture model for CPB and compared the effects of hypothermia on the inflammatory response in the coculture model with results from a clinical prospective randomized trial. The coculture model consisted of endothelial cells and monocytes. Cells were stimulated with tumor necrosis factor (TNF)-α and exposed to deep hypothermia (20°C) or normothermia (37°C). In the clinical trial, 20 patients undergoing CPB for ventricular septum defect receive either normothermic (37°C) or mild hypothermic (32°C) CPB. We observed a significant interleukin (IL)-6 and IL-8 release in the coculture model 2 and 24 h after the experimental start. In the clinical trial, cytokines were significantly increased directly after weaning from CPB and remained elevated until 24 h. IL-8 and IL-6 secretions were similar in the hypothermic and normothermic group of the coculture model and the patients after 24 h. These results demonstrate that the inflammatory reaction observed in our coculture model is comparable with the cytokine increase in the blood of children undergoing CPB. Our coculture model could be useful for studies on the mechanisms of CPB-induced inflammation.

Effects of a comprehensive blood-sparing approach using body weight-adjusted miniaturized cardiopulmonary bypass circuits on transfusion requirements in pediatric cardiac surgery.

OBJECTIVES: Transfusion-free pediatric cardiac surgery remains a challenge, mainly owing to the mismatch between the cardiopulmonary bypass (CPB) priming volume and the infants' blood volume. Within a comprehensive blood-sparing approach, we developed body weight-adjusted miniaturized CPB circuits with priming volumes of 95, 110, and 200 mL for, respectively, infants weighing less than 3 kg, 3 to 5 kg and 5 to 16 kg. We analyzed the effects of this approach on transfusion requirements and risk factors predisposing for blood transfusion. METHODS: A total of 288 children with body weights between 1.7 and 15.9 kg were included and divided into 3 groups: No transfusion, postoperative transfusion only, and intraoperative and postoperative transfusion. Groups were compared by analysis of variance or analysis of variance on ranks. Risk factors predisposing for transfusion were identified by multivariate logistic regression. RESULTS: Of the infants, 24.7% required no transfusion, 23.6% received postoperative transfusion only and 51.7% received intraoperative and postoperative transfusion. Groups differed by age, body weight, and size and by duration of surgery, CPB, and aortic crossclamp (P<.00001). Body weight (P<.00001), CPB duration (P<.00001), and persisting cyanosis (P=.03) were predictors of intraoperative and postoperative transfusion, whereas body weight (P=.00095), reoperations (P=.0051), and cyanotic heart defects (P=.035) were associated with postoperative transfusion only. CONCLUSIONS: Our blood-sparing approach allows for transfusion-free surgery in a substantial number of infants. The strongest predictors of transfusion requirement, body weight and complexity of surgery as reflected by CPB duration, are not amenable to further improvements. Better preservation of the coagulatory system might allow for reduction of postoperative transfusion requirements.

Mechanical circulatory support of systemic ventricle in adults with transposition of great arteries.

We report the successful use of the implantable ventricular assist device HeartWare (HeartWare International Inc., Framingham, MA) to support the systemic circulation in two adult patients with transposition of the great arteries (TGA). One had undergone the Senning procedure as a neonate; the other had congenitally corrected TGA and dextrocardia with palliation in adulthood. It is possible to implant the HeartWare pump into the morphological right ventricle with cannulation of either the diaphragmal surface or the free wall without additional changes in implantation technique and employing off-pump insertion.

Influence of size disparity of transplanted hearts on cardiac growth in infants and children.

OBJECTIVE: We aimed to evaluate the influence of size disparity of the transplanted heart on cardiac growth in infant and child recipients by comparing donor body surface area (BSA) and cardiac dimensions during transplantation to the corresponding parameters of the recipient over a period of time. METHODS: A retrospective review of medical and echocardiographic records of 147 children (5.3 ± 4.0; median, 4.1; range, 1 month-15 years) who underwent orthotopic heart transplantation was done. The patients were divided into age groups as follows: less than 1 year (n = 23), 1 to 2 years (n = 26), more than 2 to 5 years (n = 18), more than 5 to 10 years (n = 27), and more than 10 to 15 years (n = 53). Donor/recipient BSA ratio was determined during transplantation. Cardiac dimensions were measured 30 days after transplantation and compared at 1 year, 2 to 5 years, and 5 to 10 years after transplantation. RESULTS: There were no significant differences in the ventricular end-diastolic diameter, volumes, and mass among those with a donor/recipient BSA ratio of less than 0.80, 0.8 to 1.2, and more than 1.2 (P = .80, .44, and .48, respectively). In all the cardiac dimensions and volumes measured, donor-recipient mismatch did not influence the continuous growth of the heart, as indicated by the measured parameters, in accordance with the recipients' increase in BSA over time. All calculated Z-scores at 1 year, 2 to 5 years, and 6 to 10 years after transplantation were normal when indexed to BSA. CONCLUSIONS: This study demonstrates that despite size disparity of a transplanted heart, it undergoes normal growth in diastolic dimensions, volumes, and myocardial mass over time as appropriate for body growth after cardiac transplantation in infants and children.

Transfusion-free complex cardiac surgery: with use of deep hypothermic circulatory arrest in a preterm 2.96-kg Jehovah's witness neonate.

In neonates, the major obstacle to transfusion-free complex cardiac surgery is the severe hemodilution that can result from the mismatch between the priming volume of the circuit and the patients' blood volume. Herein, we report the case of a 13-day-old, 2.96-kg preterm neonate who had a hypoplastic aortic arch and atrial and ventricular septal defects. At the insistence of her Jehovah's Witness parents, we performed corrective surgery without transfusing homologous blood products--using deep hypothermic circulatory arrest in the process. A specially designed cardiopulmonary bypass circuit with a priming volume of only 95 mL was the key component of an interdisciplinary effort to avoid transfusion while maintaining the patient's safety. To our knowledge, this is the 1st report of the use of deep hypothermic circulatory arrest in blood-transfusion-free surgery to correct congenital heart defects in a small Jehovah's Witness neonate.

Adaptive growth and remodeling of transplanted hearts in children.

OBJECTIVE: We aimed to evaluate the adaptive growth and remodeling behavior of the transplanted heart in pediatric heart-transplant recipients by comparing donor body surface area (BSA) and cardiac dimensions during transplantation with the corresponding parameters of the recipient over a period of time. METHODS: A retrospective review of medical and echocardiographic records of 167 children (8.65 ± 5.98, median 9; range 0-17 years) who underwent orthotopic heart transplantation between 1987 and March 2010 was done. RESULTS: In the first 30 days post-transplantation, right- and left-ventricular end-diastolic diameters, volumes, and myocardial mass were found to be significantly increased (z score 3.96, p < 0.000) in relation to the recipients' BSA. Within the first year of post-transplantation, there was a significant reduction in the right-ventricular diameter (z score, -1.0 to +1.6, p = 0.000), left-ventricular diameter (z score -1.0 to +1.9, p = 0.000), right-ventricular end-diastolic volume (z score -1.3 to +1.9, p = 0.000) and left-ventricular end-diastolic volume (z score -1.3 to +1.8, p = 0.000), right-ventricular mass (z score, -1.4 to +1.7, p = 0.000) and left-ventricular mass (z score, -1.4 to +1.8, p = 0.000). During subsequent follow-up periods of 2-5 and 6-10 years, the aforementioned cardiac dimensions and volumes increased appropriately in accordance to the BSA (p = 0.000). In all the cardiac dimensions and volumes measured, donor-recipient mismatch did not influence the continuous growth of the measured parameters, which was in accordance to the recipients' BSA over time. Kaplan-Meier survival analysis showed a survival rate of 61.7% at 10 years. There is no statistically significant difference in survival rate among patients with varying donor-recipient weight ratios and donor-recipient BSA ratios (p = 0.53). CONCLUSIONS: This study demonstrates that the transplanted heart undergoes remodeling processes and grows adaptively, in accordance to the BSA, over a period of time.

Biventricular circulatory support with two miniaturized implantable assist devices.

BACKGROUND: Up to 30% of patients with end-stage heart failure experience biventricular failure that requires biventricular mechanical support. For these patients, only bulky extracorporeal or implantable displacement pumps or the total artificial heart have been available to date, which enables only limited quality of life for the patients. It was our goal to evaluate a method that would allow the use of 2 implantable centrifugal left ventricular assist devices as a biventricular assist system. METHODS AND RESULTS: Seventeen patients have been implanted with 2 HeartWare HVAD pumps, 1 as a left ventricular assist device and 1 as a right ventricular assist device. Seventy-seven percent of the patients had idiopathic dilated or ischemic cardiomyopathy. Their age ranged from 29 to 73 years (mean 51.8 ± 14.5 years), and 11 (64.7%) received intravenous catecholamine support preoperatively. The right ventricular assist device pump was implanted into the right ventricular free wall. The afterload of this pump was artificially increased by local reduction of the outflow graft diameter, and the effective length of its inflow cannula was reduced by the addition of two 5-mm silicon suture rings to the original HVAD implantation ring. All right ventricular assist device devices could be operated in appropriate speed ranges and delivered a flow of between 3.0 and 5.5 L/min. Thirty-day survival was 82%, and 59% of the patients could be discharged home after recovering from the operation. There was no clinically relevant hemolysis in any of the patients. CONCLUSIONS: Two HeartWare HVAD pumps can be used as a biventricular assist system. This implantable biventricular support gives the patients more comfort and mobility than usual biventricular ventricular assist devices with large and noisy displacement pumps.

[Technical possibilities and limitations of mechanical circulatory support]. / Herzinsuffizienz - Technische Möglichkeiten und Grenzen der Mechanischen Kreislaufunterstützung.

Ventricular assist devices (VAD) to support the left (LVAD), the right (RVAD) or both ventricles (BVAD) have emerged as one standard of care for advanced heart failure patients. Initially used to bridge patients to transplantation (BTT) they are now more frequently implanted as permanent support (destination therapy, DT). Bridge to recovery (BTR) is a valid option for only a small number of patients. Although there are different devices available, patient selection, preoperative and intraoperative management, and the timing of VAD implantation are the elements critical to successful circulatory support.