experience of personalized treatment of pediatric patients with implanted left ventricular assist devices in the early postoperative period

In adult patients, continuous-flow mechanical circulatory support devices completely prevail over pulsatile ones, representing more than 90 %. With the constant miniaturization of devices, the number of proposals of pediatric cardiologists regarding the use of continuous-flow ventricular assist devices (VAD) in children is growing. According to the first PediMACS report, approximately half (54 %; 109 of 200) of registered long-term devices are continuous-flow devices. This article describes the current state of the children’s continuous-flow system for mechanical circulatory support and evaluates the prospects for its future use. The strategy of the Silesian Center for Heart Diseases in the early postoperative period was very similar to that used in patients after Fontan procedure, including special tactics of respiratory support, adding nitric oxide or leaving the chest open after the start of circulation support. Despite aggressive management, a certain part of the patients had right ventricular failure, which required temporary mechanical support to restore blood flow in the pulmonary circulation and increase left ventricular preload. Early biventricular support correlates with better survival compared to its delayed use. Thus, a thorough preoperative risk assessment of right ventricular failure is required for implantation of biventricular assist device or for heart transplantation.

Оригінальні дослідження / Original Researches all durable VAD implants in the PediMACS 2016 third quarter report [3]. In this commentary, we describe the current state of pediatric continuous-flow VAD support, and discuss perspectives regarding its future use.
There is no doubt that continuous-flow VAD technology has a profoundly positive impact on the outcomes of VAD support in the adult population [4]. It is plausible that nearly adult-sized adolescents would have equally excellent outcomes with continuous-flow VADs that were intended for use in adults [5]; however, it is premature to assume that continuous-flow VADs would have a similar impact across the spectrum of body sizes in the pediatric population. Although anecdotal reports with continuous-flow VADs in children are rather encouraging, careful evaluation of available outcomes data is warranted before definitive conclusions can be drawn. Nonetheless, whether smaller children will also experience comparable outcomes with adult-sized continuousflow VADs remains to be seen. A major concern with the use of continuous-flow VADs in smaller children is a patient-device size mismatch [6], particularly because all currently available continuous-flow VADs are designed for adult patients. A recent multi-institutional study evaluating outcomes after implantation of the HVAD system (Medtronic, Minneapolis) in children with a body surface area (BSA) of < 1.0 m 2 showed a favorable survival rate, but with a high incidence of complications, including pump thrombosis [7]. Conway et al. conducted a worldwide survey evaluating the outcome of the HVAD use in children [8]. This study, involving 250 patients from 35 sites in 12 countries, demonstrated a tendency toward poorer outcomes in smaller children; the mortality rate at age < 12 months was 15.6 % (95% confidence interval, 3.96-28.93 %) in children weighing < 25 kg and 7.6 % (95% confidence interval, 6.2-28.9 %) weighing > 25 kg. Although the observed difference in mortality did not reach statistical significance, it warrants close attention from a clinical standpoint. Anecdotally, it is known that both weight and the shape of the chest wall are important factors in successful VAD implantation in children; a smaller child with a broad chest may be a more suitable candidate than a bigger child with a narrow chest. Evaluation by "virtual implantation" such as that used for total artificial heart implantation [9] may provide useful guidance in determining compatibility. Nonetheless, the smaller the heart, the more significant the size mismatch between the patient and the device.

materials and methods
Between 2016 and 2017, three pediatric patients were implanted with CF-LVAD at the Department of Pediatric Cardiac Surgery, Silesian Center for Heart Diseases (Zabrze, Poland). The indications for initiating MCS were end-stage congestive heart failure due to dilated cardiomyopathy (CMP) in all the patients. Taking into consideration the size of devices, the HeartWare System (HeartWare Inc., Miami Lakes, FL) was chosen for implantation. The system has been previously described in details. Briefly, it consists of a centrifugal pump, an integrated inflow cannula, an outflow graft, and a percutaneous driveline connected to an electronic controller. The pump has the displacement volume of 50 cc and weighs 140 g. The diameter of the pump is 49 mm, the total height is 58 mm. The inflow part has a diameter of 20.5 mm and is 25 mm long. The outflow tube has a diameter of 10 mm, and the percutaneous driveline -a diameter of 4.2 mm. All the implantations were carried out with cardiopulmonary bypass (CPB). A standard median sternotomy was performed during the surgical procedure. The patient was put on cardiopulmonary bypass after sewing the ring to the myocardium and coring the ventricular wall, the inflow cannula was inserted slightly anteriorly to the left ventricular apex. The outflow graft was anastomosed to the ascending aorta using partial clamping. The driveline was then tunneled under the sternum to the right upper abdominal quadrant and connected to the controller. The position of CF-LVAD with respect to the heart could be observed on postoperative chest X-rays of patients. All of them were supported with CF-LVAD alone, despite the fact that they had a

Notes: LVEDD -left ventricular end-diastolic diameter; LVEF -left ventricular ejection fraction.
high degree right heart dysfunction [10]. In general, the management strategy was similar to that used in patients with Fontan procedure, including nitric oxide application, a special technique of ventilation and even leaving the chest open in the early post-implantation period. A transesophageal and subsequently transthoracic echocardiography were used as a primary tool for monitoring ventricular function and optimization of pump speed while weaning the patient from cardiopulmonary bypass following implantation, and for further adjustments.

results
Patients' demographic and preoperative characteristics are listed in Table 1. All the patients met the criteria for INTERMACS score 1 before CF-LVAD implantation. Of three patients forming the study cohort, all received intravenous inotropes prior to CF-LVAD implantation, two were on prolonged mechanical ventilation, while one patient was supported with venousarterial ECMO. Two patients needed resuscitation procedures to be performed several times.
Clinical outcomes are summarized in Table 2. All the patients remained on VAD support as a bridge-to-transplant. Patient 1 and 2 have been on VAD support over 550 days and continue to be supported. The postoperative chest X-ray images are shown in Fig. 1. None of the patients have developed significant end-organ dysfunction, either in early or long-term follow-up. In none of our patients we have observed symptoms of device malfunction. In patient 1 and 3, signs of depression and feeding intolerance were detected.
In all the patients, only LVAD system was implanted in spite of biventricular dysfunction. The prolonged cardiopulmonary bypass time (Table 2) was due to right ventricular dysfunction and attempts to eliminate the implantation of the right ventricular assist device. Postoperative anticoagulation was started with unfractionated heparin (the target activated partial thromboplastin time of 50 to 60 s). As the patients tolerated oral nutrition, heparin was switched to warfarin. The target international normalized ratio (INR) for this cohort was well within the recommended range of 2-3. The platelet inhibitor used was acetylsalicylic acid 1 to 2 mg/kg/day. All the patients and their families were trained prior to discharge home. All the patients received treatment after discharge including metildigoxin, aspirin and acenocoumarol with the dose adjusted according to INR. Patients 2 and 3 additionally received sildenafil, angiotensin-converting enzyme inhibitors and occasionally furosemide. The patients were advised to check INR, initially every 2 days, then on a weekly basis. Readmission occurred two times in patient 1 and one time in patient 2. In patient 1, driveline infection (defined as appearance of erythema or purulent drainage around driveline exit site) was the cause of several readmissions. CF-LVAD-related thrombosis or signs of stroke were not present in any patient. Supraventricular arrhythmia was observed postoperatively in patients 2 and 3, but only in the early post-implantation period. An emergency reference card displaying contact telephone numbers and an algorithm for emergency care was provided to all the patients. Before reintegration to school, school staff members were educated by the family caregiver.

discussion
In this study, we have demonstrated that children with low weight and BSA < 1.5 m 2 can be successfully implanted with CF-LVAD and supported for long periods. Moreover, all our pediatric patients have been discharged home and attended their schools [6]. There is a growing body of evidence that CF-LVAD is currently the optimal method of long-term MCS, even in pediatric patients. The borderline body weight, when the patients can be supported, is about 20 kg, whereas the pulsatile systems, such as Berlin Heart, remains the option for patients with lower body weight, when the volume of the employed paracorporeal pumps is adjusted to the body mass. One of the major advantages of CF-LVAD systems is the possibility of discharging patients home; they can even attend schools and be active in everyday life. All the patients in our group are physically very active, what may even pose a risk of damaging the driveline. They demonstrated end-stage congestive heart failure, with enhanced pharmacothe rapy, being on mechanical ventilation, and in one case on ECMO as a bridge to CF-LVAD. It seems to be one of the causes that the time from admission to discharge home was about one month. With the center gaining experience, the threshold for starting MCS may be optimized, so that the patients might be implanted with CF-LVAD before reaching the critical status, that may influence the post-implantation course. Some data suggest that ECMO should be generally viewed as increasing the risk of LVAD support in the majority of children. On the other hand, it is possible that ECMO [11], when used strictly for short-term resuscitative support to normalize end-organ function immediately prior to VAD implant, may improve LVAD candidacy in selected patients. Patients with significant problems due to left ventricular function very frequently have a concomitant right ventricular dysfunction, so the decision must be reached whether the patient needs LVAD only or biventricular MCS system implantation. The biventricular system is highly demanding and is associated with poorer final results. That is why the majority of centers prefer to start only LVAD and manage patients with right ventricular failure using pharmacological support. Appreciating this strategy, we dedicated much effort to preventing biventricular MCS, which was the cause of prolonged time of cardiopulmonary bypass, which was not related to technical issues of CF-LVAD implantation.
In our experience, the management strategy in the postoperative period was very similar to that in patients after Fontan procedure, including special ventilation settings, nitric oxide administration, or even leaving the chest open shortly after initiation of MCS. Despite aggressive medical support of right ventricle, a certain proportion of patients will still develop right ventricular failure requiring temporary mechanical support to restore blood flow to the pulmonary circulation and increase left ventricular preload [7]. Studies suggest that an early planned biventricular assist device is associated with better survival compared to delayed implantation [8,9]. Therefore, performing a thorough preoperative risk assessment for right ventricular failure is necessary to implant biventricular assist device or total artificial heart.