Graphene Oxide Significantly Modifies Cardiac Parameters and Coronary Endothelial Reactivity in Healthy and Hypertensive Rat Hearts Ex Vivo.

Interactions of graphene oxide (GO) with an ex vivo rat heart and its coronary vessels have not been studied yet. Moreover, the conflicting data on the "structure-properties" relationships do not allow for biomedical applications of GO. Herein, we study the impact of GO on the ex vivo isolated rat heart, normotensive and hypertensive, under the working heart and the constant-pressure perfusion (Langendorff) regimes. Four structural GO variants of the following initial morphology were used: few-layer (below 10-layer) GO1, O < 49%; predominantly single-layer GO2, O = 41-50%; 15-20-layer GO3, O < 11%; and few-layer (below 10-layer) NH4 +-functionalized GO4, O < 44%, N = 3-6%. The aqueous GO dispersions, sonicated and stabilized with bovine serum albumin in Krebs-Henseleit-like solution-uniformized in terms of the particle size-were eventually size-monodisperse as revealed by dynamic light scattering. To study the cardiotoxicity mechanisms of GO, histopathology, Raman spectroscopy, analysis of cardiac parameters (coronary and aortic flows, heart rate, aortic pressure), and nitric oxide (NO-)-dependent coronary flow response to bradykinin (blood-vessel-vasodilator) were used. GO1 (10 mg/L) exerted no effects on cardiac function and preserved an increase in coronary flow in response to bradykinin. GO2 (10 mg/L) reduced coronary flow, aortic pressure in normotensive hearts, and coronary flow in hypertensive hearts, and intensified the response to bradykinin in normal hearts. GO3 (10 mg/L) reduced all parameters in hypertensive hearts and coronary response to bradykinin in normal hearts. At higher concentrations (normotensive hearts, 30 mg/L), the coronary response to bradykinin was blocked. GO4 (10 mg/L) reduced the coronary flow in normal hearts, while for hypertensive hearts, all parameters, except the coronary flow, were reduced and the coronary response to bradykinin was blocked. The results showed that a low number of GO layers and high O-content were safer for normal and hypertensive rat hearts. Hypertensive hearts deteriorated easier upon perfusion with low-O-content GOs. Our findings support the necessity of strict control over the GO structure during organ perfusion and indicate the urgent need for personalized medicine in biomedical applications of GO.

The european registry for patients with mechanical circulatory support (EUROMACS): fourth paediatric EUROMACS (Paedi-EUROMACS) report.

OBJECTIVES: The use of ventricular assist devices in children is increasing. However, absolute numbers in individual centers and countries remain small. Collaborative efforts such as the Paedi-EUROMACS are therefore essential in order to combine international experience with paediatric ventricular assist devices. In this paper, the results from the fourth Paedi-EUROMACS report are presented. METHODS: All paediatric (<19 years) patients supported by a ventricular assist device from the EUROMACS database were included. Patients are stratified into a congenital heart disease group and a group with a non-congenital aetiology. Endpoints included mortality, transplantation and recovery. Cox proportional hazard models were used to explore associated factors for mortality, cerebrovascular accident, and pump thrombosis. RESULTS: 590 primary implantations were included. The congenital group was significantly younger (2.5 versus 8.0 years respectively, p < 0.001) and were more commonly supported by a pulsatile flow device (73.5% vs 59.9%, p < 0.001). Mortality was significantly higher in the congenital group (30.8 vs 20.4%; p = 0.009) than in the non-congenital group. However, in multivariable analyses, congenital heart disease was not significantly associated with mortality (HR 1.285, CI 0.8111-2.036, p = 0.740). Pump thrombosis was the most frequently reported adverse event (377 events in 132 patients; 0.925 events per patient-year) and was significantly associated with BSA (HR 0.524 CI 0.333-0.823, p = 0.005), congenital heart disease (HR 1.641 CI 1.054-2.555, p = 0.028) and pulsatile flow support (HR 2.345 CI 1.406-3.910, p = 0.001) in multivariable analyses. CONCLUSIONS: This fourth Paedi-EUROMACS report highlights the increasing use of paediatric ventricular assist devices. The patient populations with congenital and non-congenital aetiology exhibit distinct characteristics and clinical outcomes.

Ventricular assist device support in paediatric patients with restrictive cardiomyopathy - Clinical outcomes and haemodynamics.

OBJECTIVES: Restrictive cardiomyopathy is rare and is generally associated with worse clinical outcomes compared to other cardiomyopathies. Ventricular assist device support for these children is seldom applied and often hampered by the surgical difficulties. METHODS: All paediatric (<19 years) patients with a restricted cardiomyopathy supported by a ventricular assist device from the EUROMACS database were included and compared to patients with a dilated cardiomyopathy (retrospective database analyses). Participating centres were retrospectively contacted to provide additional detailed echo and Swan Ganz measurements to analyse the effect of ventricular assist device support on pulmonary artery pressure and right ventricular function. RESULTS: Forty-four paediatric ventricular assist device-supported patients diagnosed with restricted cardiomyopathy were included, with a median age at implantation of 5.0 years. Twenty-six of the 44 patient with a restricted cardiomyopathy survived to transplantation (59.1%), 16 died (36.4%) and 2 are still on ongoing VAD support (4.5%) after a median duration of support of 95.5 days (IQR 33.3-217.8). Transplantation probability after 1 and 2 years of ventricular assist device support in patients with a restricted cardiomyopathy were comparable to patients with a dilated cardiomyopathy (52.3% vs 51.4% and 59.5% vs 60.1%, p = 0.868). However, mortality probability was higher in the restricted cardiomyopathy cohort (35.8% vs 17.0% and 35.8% vs 19.0%, p = 0.005). Adverse event rates were high (CVA in 31.8%, pump thrombosis in 29.5%, major bleeding 25.0%, eventual biventricular support in 59.1%). In the atrially cannulated group, CVA and pump thrombosis occurred in twice as much patients (21.1% vs 40.0%, p = 0.595 and 15.8% vs 40.0%, p = 0.464; probably non-significant due to the small numbers). Pulmonary arterial pressures improved after implantation of a ventricular assist device, and six patients who were initially labelled as ineligible due to pulmonary hypertension could eventually be transplanted. CONCLUSIONS: Ventricular assist device support in children with a restricted cardiomyopathy is rarely performed. Mortality and adverse event rates are high. On the other hand, survival to cardiac transplantation was 59.1% with all patients surviving the first 30 days after cardiac transplantation. Pulmonary arterial pressures improved while on support, potentially making cardiac transplantation a viable option for previously ineligible children.

Systemic Sclerosis as a Challenge for Heart Transplantation: A Case Report.

OBJECTIVE: To assess the principles of qualification and the range of organ transplantation in a patient with diagnosis of system sclerosis with pulmonary manifestation and severe myocardial insufficiency. METHODS: We present the case of a 43-year-old patient with confirmed systemic sclerosis with pulmonary manifestations and biventricular heart insufficiency after disease exacerbation and sudden cardiac arrest in the pulseless electrical activity (PEA) mechanism with effective resuscitation, with increasing shortness of breath and the need for inotropes and levosimendan infusion without a significant improvement in his general status. Owing to the diagnosis of a systemic disease with no option for pharmacologic or any other treatment for heart failure, he was reevaluated and put on an urgent waiting list for isolated heart transplantation. After 7 days, heart transplantation was performed. Given the risk of disease progression and the possibility of future lung transplantation, the pleural cavities were untouched. The standard immunosuppression protocol was followed with the use of rabbit antithymocyte globulin. RESULTS: The patient was extubated at 24 hours after heart transplantation. The results of endomyocardial biopsies performed during the hospital stay and at a 6-month follow-up were negative. The patient was discharged to home after 22 days of an uneventful hospital stay. CONCLUSIONS: Scleroderma as an autoimmunologic disease remains a challenge for the transplantation team as a possible progressive multiorgan insufficiency requiring qualification for organ transplantation. The course of the disease varies depending on the form of systemic sclerosis. Careful assessment, qualification, and determination of appropriate preprocedure and postprocedure immunosuppressive treatment are essential to an uncomplicated course of treatment.

Utility of 64-Slice Coronary Computed Tomography Angiography in Heart Transplant Recipients.

BACKGROUND: Graft vasculopathy is a leading cause of death after heart transplantation (HTx). Diagnosing cardiac allograft vasculopathy (CAV) within this patient group poses significant challenges. This study aimed to evaluate the safety and efficacy of coronary computed tomographic angiography (CCTA) in patients after HTx. METHODS: We enrolled 107 consecutive HTx recipients (26 women, mean age 50 ± 17 years); all were ≥3 years post-HTx with minimal or no evidence of CAV in a prior coronary angiography performed a minimum of 2 years before the current examination. The inclusion criteria comprised an estimated glomerular filtration rate (eGFR) of ≥30, absence of new heart failure symptoms, and no contraindications to iodine contrast or CT scans. All patients underwent a 64-slice CCTA. In cases of minimal or no changes, noninvasive follow-up examinations were conducted. Significant changes in CT prompted additional coronary angiography. RESULTS: Of the enrolled participants, 9 exhibited minimal changes; 98 displayed no changes in coronary angiography. The median time since transplant was 7 years, with IQR of 4 to 11.25 years. Significant changes were excluded in 98 patients. Among the 9 patients with suspected significant CAV, significant changes were confirmed in 8 patients, resulting in percutaneous transluminal coronary angioplasty (PTCA) performed in 6. One patient from this group died shortly after PTCA. No cardiovascular incidents were observed within the remaining group. The median follow-up period was 539 (IQR = 289-654 days). The mean left ventricular ejection fraction at follow-up was 58% ± 5% compared with 58% ± 4% at baseline. At follow-up, the mean eGFR was 64 ± 18 mL/kg/1.73 m2 compared with the baseline value of 67.2 mL/kg/1.73 m2. CONCLUSIONS: CCTA appears to offer a secure and efficient means of assessment in HTx recipients.

Assessment of Selected Parameters of Heart Donors and Recipients and Their Impact on the Transplantation Result.

OBJECTIVE: To evaluate the impact of heart donors and recipients parameters on the outcomes after orthotopic heart transplantation (OHT). METHODOLOGY: Two hundred fifteen patients who underwent OHT from 2020 to 2023 were analyzed. RESULTS: Average donors age 36.3 (±13.1) years, 74 women (34.42%), BMI 25.3 (±4.99), Na+ concentration 153.7 (±11.8) mmol/L. Mean intraventricular septum thickness 10.0 (±2.2) mm, left ventricular end-diastolic diameter 44.3 (±6) mm, ejection fraction 60.3 (±7.92) %. Median procalcitonin was 0.6 ng/mL. Levonor was used in 75.8%, Empressin in 4.2%, Dopamine in 5.1%, Dobutamine in 3.7%, and Adrenaline in 3.7% of donors. The most common cause of death: intracranial injury (34.42%). Cardiopulmonary resuscitation occurred in 34%, alcoholism in 20.9%, nicotinism in 16.3%, and drug addiction in 7.4% of donors. Mean aortic cross-clamping time was 200.3 (±48.8) minutes. Intra-aortic balloon pump (IABP) after OHT required 6.1%, extra corporeal membrane oxygenation (ECMO) 6.1%, and renal dialysis 36% of recipients. The 1-year mortality rate was 19.1%. Death after OHT correlated with: longer aortic cross-clamping time (207.6 vs 198.59 minutes, P = .292), longer extracorporeal circulation time (196.3 vs 186.47 minutes, P = .335), lower Empressin dose (median 0.01 vs 0.02 j.m/min, P = .03) in donors, longer postoperative mechanical ventilation (mean 101.46 vs 23.09 hours, P = .001), more frequent dialysis, IABP or ECMO (P = .001) and older age of the recipient (51.2 vs 44.8 years, P = .014). Previous cardiac surgery or any surgical intervention after transplantation significantly influenced mortality. The remaining donor factors had no impact on the OHT result. CONCLUSIONS: Identification of risk factors in the donor and recipient may improve treatment outcomes after OHT.

Mechanical circulatory support in patients with congenital heart disease: a European Registry for Patients with Mechanical Circulatory Support (EUROMACS) study.

OBJECTIVES: This study aims to explore characteristics and clinical outcomes of patients with congenital heart disease (CHD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). METHODS: This is a retrospective study of EUROMACS participants receiving MCS as bridge-to-transplant, possible bridge-to-transplant, or rescue therapy/bridge-to-recovery from 2011 to 2023 (n = 5340). Adult and paediatric cohorts were analysed separately. The primary outcome was mortality on MCS; secondary outcomes included recovery, transplant and complications including bleeding, cerebrovascular events, and sepsis. RESULTS: Among adult patients, mortality at 1-year was 33.3% among the CHD cohort vs 22.1% in the non-CHD cohort. Adult CHD patients had higher hazards of mortality within the first year after MCS implantation [hazard ratios 1.98, 95% confidence interval (CI) 1.35-2.91, P < 0.001] and bleeding events (subdistribution hazard ratios 2.10, 95% CI 1.40-3.16, P < 0.001) compared with non-CHD patients. Both associations remained significant after accounting for multiple mediators. Among paediatric patients, mortality at 1 year was 22.1% in the CHD cohort vs 17.3% in the non-CHD cohort (hazard ratios 1.39, 95% CI 0.83-2.32, P = 0.213). CONCLUSIONS: Adult and paediatric patients with CHD on MCS have higher adverse event risk compared with non-CHD MCS patients, though children did not have greater risk of mortality. As the number of CHD patients requiring advanced heart failure management continues to grow, these findings can enhance informed decision-making. CLINICAL TRIAL REGISTRATION NUMBER: Registry name: EUROMACS.

Durable left ventricular assist device explantation following recovery in paediatric patients: Determinants and outcome after explantation.

OBJECTIVES: Myocardial recovery in children supported by a durable left ventricular assist device is a rare, but highly desirable outcome because it could potentially eliminate the need for a cardiac transplant and the lifelong need for immunosuppressant therapy and the risk of complications. However, experience with this specific outcome is extremely limited. METHODS: All patients < 19 years old supported by a durable left ventricular assist device from the European Registry for Patients with Mechanical Circulatory Support database were included. Participating centres were approached for additional follow-up data after explantation. Associated factors for explantation due to myocardial recovery were explored using Cox proportional hazard models. RESULTS: The incidence of recovery in children supported by a durable left ventricular assist device was 11.7% (52/445; median duration of support, 122.0 days). Multivariable analyses showed body surface area (hazard ratio 0.229; confidence interval 0.093-0.565; P = 0.001) and a primary diagnosis of myocarditis (hazard ratio 4.597; confidence interval 2.545-8.303; P < 0.001) to be associated with recovery. Left ventricular end-diastolic diameter in children with myocarditis was not associated with recovery. Follow-up after recovery was obtained for 46 patients (88.5%). Sustained myocardial recovery was reported in 33/46 (71.7%) at the end of the follow-up period (28/33; >2 year). Transplants were performed in 6/46 (11.4%) (in 5 after a ventricular assist device was reimplanted). Death occurred in 7/46 (15.2%). CONCLUSIONS: Myocardial recovery occurs in a substantial portion of paediatric patients supported with durable left ventricular assist devices, and sustainable recovery is seen in around three-quarters of them. Even children with severely dilated ventricles due to myocarditis can show recovery. Clinicians should be attentive to (developing) myocardial recovery. These results can be used to develop internationally approved paediatric weaning guidelines.

Pediatric Heart Transplantation in the Context of Severe Pulmonary Hypertension Secondary to Restrictive Cardiomyopathy-Case Report.

The aim of this study is to analyze the feasibility of performing an isolated heart transplant in patients with severe pulmonary hypertension as a result of restrictive cardiomyopathy. The results present the clinical course from the diagnosis of restrictive cardiomyopathy at the age of 2 until the heart transplant at 8 years old. Initially, the patient was considered for multiorgan transplantation, heart and lungs, due to extremely high pulmonary resistance. However, due to the prolonged waiting period for a donor and the worsening condition of the child, a decision was made to perforate the atrial septum with the implantation of an atrial flow regulator system. After conducting control hemodynamic measurements, the qualification was changed to an isolated heart transplant, accepting the high operative risk associated with the still elevated pulmonary resistance index of 4.9 Wood units. This study describes the medical problems that occurred during postoperative treatment. The patient underwent an orthotopic heart transplant in her eighth year of life. Postsurgery, complications were observed, including generalized seizures and heart transplant rejection reaction. Immunosuppressive therapies were applied, and efforts were made to combat anemia and electrolyte disorders. While the cardiovascular system and heart parameters improved, there were some difficulties in controlling heart rhythm and stabilizing electrolyte levels.

Case Report: Heart aneurysm of unknown origin in a two-year-old child diagnosed in the course of Multisystem Inflammatory Syndrome in Children.

We present a case of a 22-month-old boy with a hypokinetic and thin-walled aneurysm of the left ventricle apex. The lesion was diagnosed during routine echocardiography examination in the course of MIS-C, and its occurrence due to MIS-C is plausible. Cardiac magnetic resonance imaging revealed an akinetic aneurysm of the LV apex with a full-wall ischemic scar. Aortography confirmed a normal course of coronary arteries, with adequate perfusion of essential branches and no evidence of stenosis or aneurysms. The boy underwent consultation with the heart team and was deemed eligible for surgery. The aneurysm was excised up to the margin of healthy tissues, and both the surgery and the periprocedural period were uneventful. Determining the origin of the aneurysm is challenging. The most probable etiology appears to be a congenital lesion. Another consideration is an ischemic lesion that may have resulted from impaired coronary circulation during the complicated course of MIS-C. It is possible that this disturbance resolved spontaneously before aortography was performed. Additionally, a complication of pericarditis cannot be entirely ruled out.

Does the induction immunotherapy (basiliximab) influence the early acute cellular rejection index after orthotopic heart transplantation?- Preliminary assessment report.

The study aimed to determine the influence of induction therapy on the acute cellular rejection (ACR) index in adult heart transplant recipients during the one-year observation. The study population consisted of 256 consecutive adult patients (pts), aged 51.5 (±11.9) years, 199 (77%) men treated with orthotopic heart transplantation (OHT) in the period between 2015 and 2020 in a single high-volume heart transplant center. The endomyocardial biopsies (EMBs) were performed according to the protocol consisting of 7 protocolary EMBs for up to 3 months and 10 EMBs for up to one year after OHT. The rejection index (ACRI) was calculated as the number of scheduled EMBs with the ACR ≥ 2 divided by the total number of protocolary EMBs. The study population was divided into two groups according to the application of basiliximab. The total number of pts. who received basiliximab was 10 (3.9%). The main indications for the usage of the induction therapy were heart retransplantation, mechanical circulatory support (MCS), severe renal insufficiency (eGFR <30 mL/min/1.73 m2), and a panel of reactive antibody (PRA) > 10%. In the group with induction, the mean age was 49 (±14) years; 3 (30%) patients had the MCS prior to OHT, and 3 (30%) patients had heart retransplantation. Four (40%) patients had diabetes mellitus, and 4 (40%) patients had severe renal insufficiency. As maintenance therapy during the observation period, tacrolimus was given to 10 (100%) patients, everolimus to 2 (20%) patients, and MPA to 9 (90%) patients. In the group with no induction, the mean age was 51.8 (±12) years, MCS was used in 56 (23%) patients, 2 (0.8%) patients were retransplanted; 10 (4%) patients had eGFR <30 mL/min/1.73 m2 and 58 (24%) patients had diabetes. Tacrolimus was administered to 243 (99%) patients, cyclosporine to 3 (1%), everolimus to 40 (16%), and mycophenolate to 245 (99.6%) heart recipients. The median one-year ACRI was 0.0, IQR:0.0-0.08 in the group with induction vs. 0.077, IQR: 0.0-0.154 with no induction; p = 0.11. ACRI up to three months was significantly higher in the entire cohort in comparison to up to one year (P < 0.01). The multivariate analysis showed that only everolimus implementation and younger age at the time of transplant influenced patients' mortality rate (P < 0.01). Significant graft rejections (≥ 2R ISHLT) are most common in the first three months after OHT. Patients who are initially at high risk of significant cellular rejection may benefit from induction therapy.

Use of Intracorporeal Durable LVAD Support in Children Using HVAD or HeartMate 3-A EUROMACS Analysis.

Purpose: The withdrawal of HVAD in 2021 created a concern for the pediatric population. The alternative implantable centrifugal blood pump HeartMate 3 has since been used more frequently in children. This paper analyses the outcome of children on LVAD support provided with an HVAD or HM3. Methods: A retrospective analysis of the EUROMACS database on children supported with VAD < 19 years of age from 1 January 2009 to 1 December 2021 was conducted. All patients with an LVAD and either an HVAD or HM3 were included. Patients with missing data on VAD status and/or missing baseline and/or follow up information were excluded. Kaplan-Meier survival analysis was performed to evaluate survival differences. Analyses were performed using Fisher's exact test. Results: The study included 150 implantations in 142 patients with 128 implants using an HVAD compared to 28 implants using an HM3. Nine patients (6%) needed temporary right ventricular mechanical support, which was significantly higher in the HM3 group, with 25% (p: 0.01). Patients in the HVAD group were significantly younger (12.7 vs. 14.5 years, p: 0.01), weighed less (45.7 vs. 60 kg, p: <0.000) and had lower BSA values (1.3 vs. 1.6 m2, p: <0.000). Median support time was 204 days. Overall, 98 patients (69%) were discharged and sent home, while 87% were discharged in group HM3 (p: ns). A total of 123 children (86%) survived to transplantation, recovery or are ongoing, without differences between groups. In the HVAD group, 10 patients (8%) died while on support, whereas in 12% of HM3 patients died (p: 0.7). Conclusions: Survival in children implanted with an HM3 was excellent. Almost 90% were discharged and sent home on the device.

Invasive Pulmonary Aspergillosis After Sars-CoV-2 Infection as Limitation of Contemporary Transplantology: A Case Report.

Invasive fungal infections are uncommon in pediatric heart transplant recipients. Risk and mortality are highest in the first 6 months post-transplant, especially in patients with previous surgery and those requiring mechanical support. There is a possibility that prior SARS-CoV-2 infection may cause a more severe course of pulmonary aspergillosis, especially in immunosuppressed individuals. This report describes a female patient, eight years of age, who was admitted to the pediatric cardiac surgery department with symptoms of end-stage heart failure in urgent need of mechanical circulatory support (MCS). A left ventricular assist device (LVAD) was implanted as a bridge to transplantation. During over a year on the waiting list, LVAD was replaced twice due to the presence of fibrin on the inlet valve. While staying in the ward, the patient underwent SARS-CoV-2 infection. An orthotopic heart transplant was successfully performed after 372 days of MCS with LVAD. One month after transplantation, the girl developed severe pulmonary aspergillosis complicated by sudden cardiac arrest and implantation of venovenous extracorporeal membrane oxygenation (VV ECMO) used for 25 days. Unfortunately, a few days after weaning from VV ECMO, the patient died due to intracerebral bleeding.

Use of implantable cardioverter-defibrillator in children supported with ventricular assist device: An analysis of data from the EUROMACS registry.

BACKGROUND: Data on the use and outcome of children on ventricular assist device (VAD) support provided with an implantable cardioverter-defibrillator (ICD) remains poor. METHODS: A retrospective analysis of the EUROMACS database on children supported with VAD < 19 years of age from January 1, 2009 to April 1, 2020. Patients with missing data on status of ICD, missing baseline and/or follow up information were excluded. The primary independent variable of interest was the concomitant presence or absence of an ICD at the time of VAD placement. Kaplan-Meier survival analysis was performed to evaluate survival differences between children on VAD with and without an ICD. RESULTS: Out of 303 patients provided with a VAD, 7% (7♀, 15♂) had an ICD implanted and formed the study group. Median age was 14 years, median weight was 43.5 kg, and median BSA was 1.39. Median Intermacs stage was 2 (range: 1-7). Seventeen patients (77%) were transplanted, 4 (18%) died while on support, and 1 (5%) was weaned from device after myocardial recovery. Median time on support was 68 days compared to 361 days in the control group (p: 0.01). Three patients underwent device exchange due to thrombus formation in the pump. There was no difference in survival between groups (p = 0.342). CONCLUSION: The presence of ICD in pediatric patients supported with a VAD is low (7%). Children on VAD support provided with an ICD do not have a survival benefit compared to children without an ICD.

Long-term results of pediatric heart transplantations: Single-center experiences.

BACKGROUND: Heart failure (HF) is characterized by significant mortality in both adults and children. Characteristics of pediatric HF are feeding problems, poor weight gain, exercise intolerance, or dyspnea. These changes are often accompanied by endocrine disorders. The main causes of HF are congenital heart defects (CHD), cardiomyopathies, arrhythmias, myocarditis, or heart failure secondary to oncological treatment. Heart transplantation (HTx) is the method of choice for treatment of end-stage HF in pediatric patients. AIMS: This article aimed to summarize the single-center experience in heart transplantation in children. METHODS: Between 1988 and 2021 in the Silesian Center for Heart Diseases in Zabrze, 122 pediatric cardiac transplantations were performed. In the group of recipients with failing Fontan circulation, HTx was performed in 5 children. The study group was evaluated for the postoperative course: rejection episodes depending on the medical treatment scheme, coinfections, and mortality. RESULTS: One-, 5-, and 10-year survival rates between 1988 and 2001 were 53%, 53%, and 50%, respectively. One-, 5-, and 10-year survival rates between 2002 and 2011 were 97%, 90%, and 87%, respectively; between 2012 and 2021 (1-year of follow-up), the survival rate was 92%. The main cause of mortality both in early and late periods after transplantation was graft failure. CONCLUSIONS: Cardiac transplantation in children remains the main method of treatment for endstage heart failure. Our results at both early and long-term posttransplant periods are comparable to those obtained in the most experienced foreign centers.

Outcomes in small children on Berlin Heart EXCOR support: age and body surface area as clinical predictive factors.

OBJECTIVES: The Berlin Heart EXCOR (BHE) offers circulatory support across all paediatric ages. Clinically, the necessary care and the outcomes differ in various age groups. The EUROMACS database was used to study age- and size-related outcomes for this specific device. METHODS: All patients <19 years of age from the EUROMACS database supported with a BHE between 2000 and November 2021 were included. Maximally selected rank statistics were used to determine body surface area (BSA) cut-off values. Multivariable Cox proportional hazard regression using ridge penalization was performed to identify factors associated with outcomes. RESULTS: In total, 303 patients were included [mean age: 2.0 years (interquartile range: 0.6-8.0, males: 48.5%)]. Age and BSA were not significantly associated with mortality (n = 74, P = 0.684, P = 0.679). Factors associated with a transplant (n = 175) were age (hazard ratio 1.07, P = 0.006) and aetiology other than congenital heart disease (hazard ratio 1.46, P = 0.020). Recovery rates (n = 42) were highest in patients with a BSA of <0.53 m2 (21.8% vs 4.3-7.6% at 1 year, P = 0.00534). Patients with a BSA of ≥0.73 m2 had a lower risk of early pump thrombosis but a higher risk of early bleeding compared to children with a BSA of <0.73 m2. CONCLUSIONS: Mortality rates in Berlin Heart-supported patients cannot be predicted by age or BSA. Recovery rates are remarkably high in the smallest patient category (BSA <0.53 m2). This underscores that the BHE is a viable therapeutic option, even for the smallest and youngest patients.

Cerebrovascular accidents in paediatric patients supported by the Berlin Heart EXCOR.

OBJECTIVES: Ventricular assist device support as a bridge to transplant or recovery is a well-established therapy in children on the cardiac transplant waiting list. The goal of this study was to investigate the incidence of and the associated factors for cerebrovascular accidents in paediatric patients supported by a Berlin Heart EXCOR. METHODS: All patients <19 years of age supported by a Berlin Heart EXCOR between January 2011 and January 2021 from the European Registry for Patients with Mechanical Circulatory Support were included. RESULTS: In total, 230 patients were included. A total of 140 (60.9%) patients had a diagnosis of dilated cardiomyopathy. 46 patients (20.0%) sustained 55 cerebrovascular accidents, with 70.9% of the episodes within 90 days after the ventricular assist device was implanted. The event rate of cerebrovascular accidents was highest in the first era (0.75). Pump thrombosis and secondary need for a right ventricular assist device were found to be associated with a cerebrovascular accident (hazard ratio 1.998, P = 0.040; hazard ratio 11.300, P = 0.037). At the 1-year follow-up, 44.4% of the patients had received a transplant, 13.1% were weaned after recovery and 24.5% had died. Event rates for mortality showed a significantly decreasing trend. CONCLUSIONS: Paediatric ventricular assist device support is associated with important adverse events, especially in the early phase after the device is implanted. Pump thrombosis and the need for a secondary right ventricular assist device are associated with cerebrovascular accidents. Furthermore, an encouragingly high rate of recovery in this patient population was shown, and death rates declined. More complete input of data into the registry, especially concerning anticoagulation protocols, would improve the data.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): third Paediatric (Paedi-EUROMACS) report.

OBJECTIVES: A third paediatric report has been generated from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). The purpose of EUROMACS, which is operated by the European Association for Cardio-Thoracic Surgery, is to gather data related to durable mechanical circulatory support for scientific purposes and to publish reports with respect to the course of mechanical circulatory support therapy. Since the first report issued, efforts to increase compliance and participation have been extended. Additionally, the data provided the opportunity to analyse patients of younger age and lower weight. METHODS: Participating hospitals contributed pre-, peri- and long-term postoperative data on mechanical circulatory support implants to the registry. Data for all implants in paediatric patients (<19 years of age) performed from 1 January 2000 to 31 December 2020 were analysed. This report includes updates of patient characteristics, implant frequency, outcome (including mortality rates, transplants and recovery rates) as well as adverse events including neurological dysfunction, device malfunction, major infection and bleeding. RESULTS: Twenty-five hospitals contributed 537 registered implants in 480 patients. The most frequent aetiology of heart failure was any form of cardiomyopathy (59%), followed by congenital heart disease and myocarditis (15% and 14%, respectively). Competing outcomes analysis revealed that a total of 86% survived to transplant or recovery or are ongoing; at the 2-year follow-up examination, 21.9% died while on support. At 12 months, 45.1% received transplants, 7.5% were weaned from their device and 20.8% died. The 3-month adverse events rate was 1.59 per patient-year for device malfunction including pump exchange, 0.7 for major bleeding, 0.78 for major infection and 0.71 for neurological events. CONCLUSIONS: The overall survival rate was 79.2% at 12 months following ventricular assist device implant. The comparison of survival rates of the early and later eras shows no significant difference. A focus on specific subgroups showed that survival was less in patients of younger age (<1 year of age; P = 0.01) and lower weight (<20 kg; P = 0.015). Transplant rates at 6 months continue to be low (33.2%).

Treatment of Pediatric Patients With COVID Infection After Heart Transplantation.

The COVID-19 pandemic that has been ongoing since the beginning of 2020 has forced health care into a difficult struggle for wellness and the lives of patients. International data and our observations show that the course of the disease in these patients is different than in the general population. Symptoms depend on the immunosuppression and severity of viremia. The period of viral replication is much longer. Our observations include 4 pediatric patients post heart transplant who became infected with the coronavirus. One patient was infected in the hospital during perioperative period. Two others required hospitalization because of the severity of symptoms, and 1 was treated on an outpatient basis. The applied treatment included the reduction of immunosuppression, low-molecular-weight heparin, amantadine or remdesivir, steroids, and supplementation with zinc and vitamins C and D. Based on the antigenic tests performed, we determined the period of active replication to be 3 to 8 weeks from the onset of the first symptoms.

Standards of Psychological Care for Pediatric Patients Awaiting Heart Transplantation and Those Requiring Mechanical Circulatory Support.

Children waiting for a heart transplant who require mechanical circulatory support often experience many months of hospitalization. This has a significant impact on their mental health and their development. Additional risk factors for these disorders are neurologic complications associated with the used treatment. To counteract developmental dysfunctions (despite successful heart transplantation) and possible disability in the sphere of mental health as well as to improve executive functions of children after a neurologic incident, there is a need for comprehensive care provided by a clinical psychologist who is a member of a multidisciplinary medical team taking care of the patient. Based on our own experience, standards of psychological care were developed for pediatric patients awaiting heart transplantation and those requiring mechanical circulatory support.