Clinical outcome of heart transplantation in children and young adults with congenital and acquired heart disease in a middle-income country: a 20-year single-center experience

doi:10.21203/rs.3.rs-4947133/v1

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Research Article

Clinical outcome of heart transplantation in children and young adults with congenital and acquired heart disease in a middle-income country: a 20-year single-center experience

https://doi.org/10.21203/rs.3.rs-4947133/v1

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Background

Orthotopic heart transplantation (OHT) has become the standard of care for children with end-stage heart failure refractory to medical or conventional surgical therapy. Despite the improvement in perioperative survival in the last decades, the long-term complications and mortality remain significant. This report examines the experience of a single center in Brazil with pediatric OHT, focusing on long-term results and mortality.

Methods

This is a retrospective study from January 2002 to December 2022. Data collection consisted of demographic data, indication, immunosuppression, main complications and mortality.

Results

There were 77 OHT in 74 patients. The median age at the time of OHT was 11.5 years (IQR 0.25–22 years). The indications for OHT were congenital heart disease in 36 (46.8%), cardiomyopathy in 35 (45.5%), and re-transplantation in 3 patients (primary diagnosis: 2 cardiomyopathy − 3.9%). There was an average of 2.2 rejection episodes/patient and 1.3 infection episodes/patient during the first year of follow-up. The most common complications were: acute kidney injury (51%), systemic hypertension (41.9%), anemia (24.3%) and type 2 diabetes (10.4%). Overall survival after 1 year of OHT was 89.6% while 5- and 10-year survival, were 80% and 59%, respectively. Despite late complications, such as infection and acute rejection, all survivors report a significant improvement in functional status.

Conclusion

Heart transplant is an acceptable therapeutic option for children and young adults in middle-upper resourced countries, with outcomes and long term follow up close to those higher resourced countries.

Heart transplantation

Pediatric. Heart Failure. Congenital Heart Disease. Cardiomyopathy

Pediatric heart transplantation was first attempted in the United States by Adrian Kantrowitz in a 17-day-old child with severe Ebstein’s anomaly in 1967, but it was not until 1984 that Denton Cooley performed a successful pediatric heart transplantation in a child who survived 13 years after the procedure [1, 2]. In Brazil, the first pediatric heart transplant was performed by Barbero-Maciel in 1992 [3].³

Orthotopic heart transplantation (OHT) has become the standard of care for children with end-stage heart failure refractory to medical or surgical therapy, whether secondary to underlying congenital heart disease (CHD) or cardiomyopathy (CMP). Because of the shortage of pediatric donors, it is restricted to patients without other viable therapeutic options [4–7].

According to the 24th pediatric heart transplantation report of the International Society for Heart and Lung Transplantation Registry (ISHLT), the number of pediatric heart transplant recipients increased worldwide as heart transplantation became more widely available. Between 2010 and 2018, a total of 210 centers performing heart transplants in pediatric recipients contributed data to the Registry. Over the same time period, the proportion of pediatric heart transplants performed outside of North America and Europe increased from 3–7.5% [4]. This suggests that heart transplantation is being performed at centers outside of high-resourced settings. By 2018, more than 14,000 procedures were reported to ISHLT with many centers reporting relatively low transplantation volume, averaging 1 to 4 pediatric heart transplants per year [7, 8].

In Brazil in 2022, 13 pediatric centers have reported data to The Brazilian Registry of Transplants, performing 32 pediatric cardiac transplantations, which represents 8.9% of all heart transplants in the country. The pediatric heart transplant rate in Brazil was 0.5 per million of the pediatric population. Organ donation rate in Brazil is still low, with an organ utilization rate of approximately 27%. As a result, the waitlist mortality for pediatric patients remains elevated at 29% [9, 10]. Despite the hurdles of low organ donation rates, high waitlist mortality and limited-resources, the Hospital Dr. Carlos Alberto Studart Gomes in Fortaleza, Brazil has performed pediatric heart transplants since 2002. The purpose of this study is to report our 20-year experience in pediatric OHT at a single center in Northeast Brazil, focusing on management, survival and long-term outcomes.

We carried out a retrospective study on 74 patients who had undergone OHT at a tertiary center in the Northeast region of Brazil (Fortaleza, Ceará), from January 2002 to December 2022. This study was reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [11]. The study was approved by the Ethics in Research Committee of our institution (CAAE 18631813500005039).

A careful review of the medical records was performed to collect demographic, clinical and surgical data about the patient population. Additional data from the preoperative period such as the use of mechanical ventilation, vasoactive medications and mechanical circulatory support was also collected. Data from follow-up included: immunosuppression, incidence rates of rejection and infection, cardiac allograft vasculopathy (CAV), lymphoproliferative disease, acute kidney injury (AKI), systemic hypertension, diabetes, anemia, graft dysfunction, indications for re-transplantation and mortality.

Surgical techniques

Organ harvesting followed a protocol that optimally addressed the needs of each recipient. Cardiac diagnoses considered for transplantation include lethal CHD for which there is no standardized treatment and end stage CMP with progressive deterioration in left ventricular ejection fraction or functional status despite optimal medical therapy; failure to grow, secondary to advanced heart failure; malignant ventricular arrythmias uncontrolled by conventional antiarrhythmic therapy and symptomatic heart failure requiring continuous inotropic or mechanical support. Standard strategies included myocardial protection by means of cardioplegia using hypothermia (4 to 8 ºC) and crystalloid HTK Custodiol® solution, with an infusion time of 6 minutes and volume between 30 and 50 ml/kg. Sutured labels were used for identification of the anterior surface of vessels and the inlet tract of right and left pulmonary veins. As dictated by the anatomy of the recipient, the heart was harvested with various portions of the adjoining vessels.

Cardiopulmonary bypass in the recipient was performed with hypothermia (28 ºC), and cannulation of the aorta, superior vena cava and right femoral vein. Cannulation of the brachiocephalic trunk or left femoral artery and superior vena cava were performed as necessary for individual anatomic variations. Generally, the unipulmonary-bicaval anastomosis technique was employed with variations as necessary to adapt to the recipient’s underlying anatomy.

Immunosuppression

In the immediate post-transplant period, all patients received induction therapy with methylprednisolone (20 to 25 mg/kg intravenously every 12 hours for 2 days, beginning intra-operatively at the end of cardiopulmonary bypass) and anti-thymocyte globulin (0.5 mg/kg/ dose IV for 7 to 10 days), according to institutional protocol. Chronic immunosuppressive regimens consisted of double immunosuppression with a calcineurin inhibitor (tacrolimus or cyclosporine) and an antiproliferative agent (azathioprine and more recently, mycophenolate mofetil (MMF) or mycophenolate sodium). Cyclosporine was initiated as a continuous intravenous (IV) infusion (0.1 to 0.2 mg/kg/ hour) in patients with preserved renal function and converted to oral administration (10–20 mg/kg/day, in divided doses every 8–12 hours). In the first two years of the heart transplantation program, azathioprine was the main antiproliferative agent (3 mg/kg orally once daily) but was eventually replaced by mycophenolate. Mycophenolate mofetil or mycophenolate sodium was given orally (125–500 mg/dose every 12 hours) when patients were taking oral medications. We use corticosteroids as part of the maintenance immunosuppression in patients with elevated risk of rejection. Episodes of acute rejection were treated with methylprednisolone bolus therapy (20–25 mg/kg BID for 4 days). Prednisone is used as chronic therapy after the first episode of rejection but is discontinued if the patient does not have another episode of rejection after six months. In cases of persistent rejection or with accompanying ventricular dysfunction, T-cell antibodies were administered.

Ganciclovir prophylaxis against cytomegalovirus (CMV) infection was administered in CMV-IgG negative recipients with CMV-IgG positive donors. We also use prophylactic therapy for toxoplasmosis- IgG negative recipients with toxoplasmosis- IgG positive donors.

Follow up

Routine follow-up was conducted by a multi-disciplinary team through scheduled consultations per protocol (once a week for the first month; every 15 days in the second and third month, once a month until 1 year and every 2–3 months for lifetime). Clinical evaluation consisted of echocardiography, chest roentgenogram (x-ray), electrocardiogram, routine laboratory tests (CBC and platelets, basic electrolytes, renal and hepatic function, triglycerides, cholesterol, glucose and pro-BNP) and immunosuppressive trough levels where appropriate. Testing for toxoplasmosis (IgG and IgM) titers, PCR for CMV and Epstein Barr virus (EBV) occurred every three months.

Acute rejection episodes were predominantly diagnosed in infants and children by echocardiography and clinical findings and, if necessary, confirmed by endomyocardial biopsy. Clinical signs of graft rejection include: alterations in baseline cardiac rhythm, signs of poor contractility (decreased function on echocardiogram. cool and mottled extremities, rales, hepatosplenomegaly, oliguria, diaphoresis); congestive heart failure (rales, hepatosplenomegaly, tachypnea, advancing global cardiomegaly, pulmonary edema and/or pleural effusion) and nonspecific signs like irritability, malaise, change in feeding pattern and change in sleeping pattern. All patients underwent routine biopsies on an annual basis. Serious infection was defined as one requiring hospitalization, intravenous antibiotics or both. Graft coronary vasculopathy was annually assessed by coronary angiography after the first year of transplantation. To monitor for PTLD, EBV PCR was collected every three months and a computed tomography was requested if there was any suspicion of malignancy.

Acute kidney injury (AKI) definitions were based on the Kidney Disease Improving Outcomes (KDIGO) criteria. Stage 1 AKI was defined as a > 50% or 0.3 mg/dl (within 48 h) increase in serum creatinine (SCr) from preoperative values, stage 2 was a 2-fold increase in SCr and stage 3 was a 3-fold increase in SCr or requiring dialysis during hospitalization [12].. Severe AKI was defined as stage 2 or 3 AKI.

Statistical analysis

Continuous variables are summarized as median and interquartile range (IQR). Categorical variables are summarized by frequency with percentage. Continuous variables were compared between cohorts using the unpaired Student t test for means of normally distributed continuous variables or the Wilcoxon rank sum tests for skewed data. The χ² or Fisher exact tests were used to compare differences in proportions among the categorical data. We compared the results between survivors and non-survivors, using 1-year post-transplant survivor to separate the groups. Survival was assessed using the Kaplan-Meier estimator.

Cumulative survival curves were constructed according to the Kaplan—Meier methods. To assess the association between clinical conditions, diagnosis and age with post-transplant survival, a Cox proportional regression model was constructed. A p < 0.05 was considered significant. Data were analyzed with SPSS for Windows, release 20 (SPSS Inc., Chicago, IL, USA).

Patient population

We identified 74 patients who underwent cardiac transplantation during the 20 years study period (Table 1). The age of the patients ranged from 3 months to 22 years (median 11.5 years, IQR: 3 months – 22 years). Two patients (2.7%) were under one year of age, 30 (39%) were between one and ten years, and 42 (54.5%) were older than 10 years of age at the time of heart transplantation. Four patients older than 18 years, with congenital heart disease, were included in our series. There was a predominance of male patients (59.7%). The majority of patients lived in the capital of the state (46%) and 14 (18.9%) were from other states.

Table 1

Baseline Characteristics prior to Transplantation
Characteristic	N (%)	Non-Survivor (N = 24)	Survivor(N = 50)	P value
Gender: Male Female	43 (58.1%) 31 (41.9%)	13 (54.2% 31 (62%)	14 (45.8%) 19 (38%)	0.52
Location prior to transplant Home Ward CICU Geographic region of residence Capital city Outside of capital city Other state	43 (58.1%) 6 (8.1%) 25 (33.7%) 33 (44.6%) 27 (36.5%) 14 (18.9%)	12 (50%) 0 12 (50%) 14 (58.3%) 4 (16.7%) 6 (25%)	32 (64%) 5 (10%) 13 (26%) 19 (31%) 23 (46%) 8 (16%)	0.51
Use of mechanical ventilation	8 (10.8%)	4 (16.7%)	4 (8%)	0.26
Use of CPAP	2 (2.7%)	2 (8.3%)	0 (0%)	0.03
Use of vasoactive drugs	27 (36.5%)	12 (46.2%)	14 (28%)	0.063
AKI requiring renal replacement therapy	8 (10.8%)	7 (29.2%)	1 (2%)	0.0001
Mechanical circulatory support	3 (4%)	1 (4.2%)	2 (4%)	0.98
Indication for transplant Congenital heart disease Glenn Univentricular * Fontan Ebstein L-TGA D-TGA + VSD + pulmonary stenosis HLHS Tetralogy of Fallot ASD + VSD Others Cardiomyopathy Complete heart block**I Rheumatic Heart Disease Re-transplant	36 (46.7%) 11 (30.6%) 6 (16.6%) 2 (5.5%) 2 (5.5%) 3 (8.4%) 1 (2.8%) 6 (16.6%) 3 (8.4%) 1 (2.8%) 1 (2.8%) 35 (45.4%) 2 (2.6%) 1 (1.3%) 3 (4%)	12 (50%) 11 (45.8%) 0 (0%) 1 (4.2%) 2	24 (48%) 24 (48%) 1 (2%) 1 (2%) 1	0.85
Note: OHT, heart transplantation; CICU: cardiac intensive care unit; CPAP, continuous positive airway pressure; AKI, acute kidney injury; RRT, renal replacement therapy; CHD, congenital heart disease; CMP, cardiomyopathy; Re-HTx; re-transplantation; L-TGA, Corrected Transposition of the great arteries; D- TGA, dextro Transposition of the great arteries; VSD, ventricular septal defect; HLHS, hypoplastic left heart syndrome; ASD, atrial septal defect. * Single ventricule without surgery, ** Complete heart block with CHD ou cardiomyopathy.

Thirty-five (45.5%) patients were transplanted due to CMP and thirty-six (46.8%) due to CHD (Table 1). Among those with CHD, 25 (69.4%) patients had single-ventricle physiology and 30/36 (83.3%) had undergone previous surgery prior to OHT. We also performed one combined heart-kidney transplantation in a 14-year-old boy with CHD (single ventricle physiology without previous surgical treatment) and end-stage renal failure (diffuse glomerulosclerosis on renal replacement therapy), with an interval of 19 hours between the procedures (heart transplant preceding the kidney transplant). The patient had no cardiac complications, but required 20 days of hemodialysis after renal transplantation.

Number of Transplantations

The average number of OHT per year for the entire period was 3.8 transplants/year. Over the most recent decade, there has been an upward trend in the number of transplants (average = 5.7 OHT/ year) (Fig. 1).

Circulatory support

The mechanical circulatory support program began in 2012 and has been used to support patients in both the pre- and post-operative period. Three patients (3.9%) have been bridged to transplant with mechanical circulatory support. These patients were in cardiogenic shock due to CMP. One patient was supported with extracorporeal membrane oxygenation (ECMO) for 12 days prior to transplant, but she died 8 hours after the procedure due to primary graft dysfunction. Another patient had a biventricular assist device (BIVAD) implanted 48 hours before transplantation and had an uneventful postoperative period. The third patient received ECMO as a bridge to OHT and was supported for 16 days. He recovered with no complications after the procedure and was discharged home after 50 days.

ECMO was used in three patients with severe graft failure after OHT. Two patients were supported for 72 hours with recovery of cardiac function and subsequently discharged from the hospital on post-operative days 43 and 26. Another patient received ECMO support 48 hours after OHT due to severe graft dysfunction but developed renal failure requiring renal replacement therapy and cardiogenic shock and ultimately died 96 hours after OHT. Two patients presented late with severe acute antibody mediated rejection and cardiogenic shock. One patient was supported with ECMO 10 years after OHT, but died after 9 days of mechanical circulatory support. The other patient used a ECMO for 11 days after 4 years of OHT, with partial recovery of cardiac function, survived and was discharged from hospital 4 months later due to post fungal infection.

Immunosuppressive therapy

The majority of patients receive tacrolimus (58.3%) and mycophenolate (93.7%) for immunosuppression. Twenty patients are on cyclosporine (41.6%). The main immunosuppressive regimen is presented in Fig. 2.

Follow up and complications

Infectious and rejection episodes were the most common complications during follow-up. The majority of patients (82%) had at least 1 episode of acute rejection (AR) Fifty-two patients (70%) had at least 1 episode of AR at 1-year follow-up. We observed an average of 2.2 (IQR 1–4) rejection episodes per patient over the 20 years of follow-up. All infections requiring treatment were included: infection rate was 2.3 episode/patients.

Graft vascular disease and lymphoproliferative disease

The majority of patients (96.1%) have remained free from coronary vasculopathy (CVD) and lymphoproliferative disease. There were three cases (2.6%) of CVD and 1 case (1.2%) of lymphoproliferative disease during the study period. Among the 3 patients with CVD, two patients underwent re-transplantation and the other one died on the waiting list. Lymphoproliferative disease was detected in a twelve-year old boy 5.3 years after transplant, who subsequently died during the treatment.

Renal dysfunction

We had 8 patients with pre-transplant severe renal dysfunction. One patient underwent a combined heart-kidney transplant, with complete recovery of renal function one-month post-operation. During this 20 years, post-transplant mortality for patients with preoperative renal failure and need of renal replacement therapy (RRT) was 87.5% while the mortality rate for patients with preoperative renal failure not requiring RRT was 30.4% (p < 0.001). Multivariate logistic regression analysis of patients demonstrated that the need of RRT before OHT was independently associated with higher post-transplant mortality (adjusted Odds Ratio (OR), 16.0; 95% Confidence Interval (CI), 1.8–138). Post-transplant, 51.3% (38/74) of patients had at least 1 episode of transient AKI. Two patients developed chronic kidney disease (CKD) with progression to ESRD requiring RRT. Both patients died due to rejection 6.5- and 7-years following transplantation.

Re-transplants

The re-transplantation rate in our series was 4%. Three (3.9%) patients were listed for re-transplantation due to cardiac allograft vasculopathy at 2, 4.5 and 6 years after first transplant (mean of 4.6 years). Two of these patients had CHD and one had a diagnosis of cardiomyopathy. The overall survival after re-transplantation was 33.3% (one patient experienced sudden death 2 years and 9 months after the re-transplantation and the other died with multiple organ failure in the early post-operative period).

Overall survival

During 20 years- follow-up, the overall mortality was 33.8% (26 patients) and the causes of death are listed in Table 4. When we compared patients who underwent OHT in the first decade with those in the second decade, there was an increased in survival (mortality 48.6% versus 22.2%, p 0,01). The median interval between transplantation and death was 3.8 years (IQR 0- 6.9 years). The 30-day survival was 95.9% (71/74). There were 8 deaths within the first-year of follow up (early mortality). The causes of early deaths were: one intraoperative death due to graft failure, seven patients (three receiving MCS) died early in the post-operative period (< 72 hours) due to multiple organ dysfunction and graft dysfunction. All other deaths occurred after one year of OHT, and the median interval between OHT and death was 6.4 years (IQR 3.6–7.4 years).

Table 4. Cause of death

Causes of death	N = 26 patients
Sudden death	5 (19.2%)
Arrhythmia	4 (15.4%)
Intraoperative death	1 (3.9%)
Rejection	5 (19.2%)
Graft dysfunction in post-operative period	7 (26.9%)
Lymphoproliferative disease	1 (3.9%)
Coronary vasculopathy	3 (11.5%)

The median follow up was 5.7 years (IQR 3.7–8.5 years), conditioned to 1-year survival. The survival rate at one, five and ten years were 89.6%; 80% and 59%.

In this population, there was no difference in overall survival between patients with a pre-transplant diagnosis of CHD and CMP (mean 9.7 ± 0.9 years and 11 ± 1.2 years, respectively; p 0.97). Figure 3.

Interpretation

Although the first successful pediatric transplant in Brazil occurred in 1992, the first transplant in Northeastern Brazil was only possible 10 years later, supported by the Adult Heart Transplant Program of our institution and the Pediatric Heart Transplant Program of the Heart Institute of São Paulo (INCOR). We report our 20-year single center experience in heart transplantation in children with congenital and acquired heart disease.

Our institution is a referral center for pediatric cardiac surgery and heart transplantation to the North and Northeast regions of Brazil. Early and late mortality have significantly improved during recent decades in pediatric patients after OHT. Reasons for this advance in the outcomes include better selection of patients, improved donor organ preservation, modifications in surgical technique and advances in perioperative care. However, several factors have continued to negatively impact post-transplant survival, including graft failure, acute rejection, coronary vasculopathy, infection, malignancy and renal failure [4–8, 13].

Infections and rejections

Rejection episodes and infection were the most common complications during our follow-up. Rejection remains one of the main post-transplant complications and although it may be more common in the first year after transplantation, it can occur in any period [14–16].. We observed an average of 2.3 ± 2.1 rejection episodes per patient over the 20 years of follow-up and seventy percent (52/74) of patients had at least one episode of acute rejection in the first year after transplantation. Nonetheless, our incidence is five times higher than that reported to the ISHLT [5]. Some factors that could contribute to this higher incidence would be a greater proportion of adolescents (potentially a risk-factor for non-adherence to treatment) and a higher percentage of patients with diagnosis of CHD, commonly associated with previous surgery and blood transfusion with higher allosensitization. Overall, the incidence of acute rejection between discharge and 1-year post-transplant has declined over time and the rate was 13.3% between 2012 and 2018, with lower incidence among recipients discharged on tacrolimus during this same period.

Due to limited resources and difficulties in obtaining routine endomyocardial biopsies and coronary angiography, the diagnosis of rejection was based on clinical and echocardiographic criteria in young children. Lack of angiography could explain lower rates of CAV diagnosis when compared to other centers in high income countries, but similar to other centers in Brazil [7, 17].

Infection remains an important cause of morbidity and mortality and accounts for approximately 12% of deaths during the first year following transplantation according to the Registry of 2017 and varies from 5.2–6.2% after one year of transplant.⁸ Our incidence rate of infections was 2.3 episodes/patients, which was slightly higher when compared to centers in well-resourced countries, potentially due to the lower socio-economic level of our population [8, 17].

Renal dysfunction

In our series, we had 8 patients (10.8%) with severe renal dysfunction before transplant and these patients had higher long-term mortality. Previous studies have demonstrated that pre-existing renal insufficiency is common and varies from 2.5 to 42% depending on the definition used. Pre-transplant renal insufficiency has a direct correlation with postoperative renal dysfunction and is associated with early and long-term mortality [18–23]. In the Twenty-fourth pediatric heart transplantation report by the ISHLT, the incidence of the use of RRT before transplant was 3.3% between 2010 and 2018, and it was associated with lower survival within 12 months after discharge (90.8% vs 72.9%, p < 0,01).⁵

Renal dysfunction is a common source of morbidity in the post-operative transplant period, with the majority of patients experiencing at least mild renal dysfunction [19, 24–26]. This is usually multifactorial (pre-transplant renal dysfunction, peri-transplant hemodynamics, graft function, rejection episodes, dehydration, infection), but is mainly related to the side-effects of long-term use of immunosuppressive drugs (especially calcineurin inhibitors - CNI) [18–24]. In the twentieth pediatric heart transplantation report (2017) from ISHLT, the need for renal replacement therapy ranges from approximately 6–17%, depending on age group [8]. Many single-center studies have shown variable progression of kidney dysfunction (with progressively higher risk associated with lower glomerular filtration rate) over time with 3–10% of heart transplant recipients developing severe renal dysfunction within 10 years post-transplantation [18–26].

Re-transplantation

The overall re-transplant rate has increased over the last few decades, rising from 0.5% between 2001 and 2009 to 2.7% between 2010 and 2018 [5]. However, re-transplantation is a significant risk factor for 1 and 5-year mortality [5]. We had three cases (4%) of re-transplantion over the last 20 years due to graft dysfunction with a survival rate of 33.3%. Coronary vasculopathy as an indication for re-transplantation and longer inter-transplant interval were associated with better survival after re-transplantation, but overall survival remains lower than for primary transplantation [7]. Feingold et al (2013) published a study in pediatric OHT with more than 4000 cases showing increased mortality due to re-transplantation, although some authors have found no difference compared to patients undergoing primary OHT [27–30]. We had a similar incidence of re-transplantation, but with only three cases, which makes comparison between groups impaired.

Circulatory Support

Due to shortage of donor organs in pediatric group, mechanical circulatory support (MCS) is now routinely utilized to provide short-term and long-term support as a bridging strategy to increase survival on the waiting list for OHT, reaching values above 50% in patients older than 1 year with DCM and 11.8 to 20.1% in patients with CHD (including ECMO, ventricular assist device (VAD) and total artificial heart) [7, 8, 31–33].

We had 3 cases (5.6%) of mechanical circulatory support (MSC) as a bridge to OHT: two patients were transplanted (one in ECMO and one using BIVAD) and one died while waiting for transplant (ECMO support). Only one patient was discharged after OHT (overall survival 33.3%). Our two deaths were in patients supported by ECMO as bridged to OHT (one before OHT and another 8 hours after OHT). Although MCS use has increased survival on the pediatric heart transplantation waiting list, post-transplant survival for patients bridged to transplant with ECMO has continued to be associated with worse survival; however, other forms of MCS (VADs) resulted in survival similar to that of patients not on MCS [7, 8, 31–36].

In our state, due to financial difficulties, the acquisition of VADs is not always possible whenever needed, which leads to a much smaller number of patients supported with mechanical circulatory support than that reported in the Registry of ISHLT [7, 8]. Circulatory assistance was also used in the postoperative period of OHT: two patients used ECMO as support for early graft dysfunction and other two were supported for rejection with severe ventricular dysfunction.

Early and late mortality

Our data represent a 20-year experience of heart transplantation in a small pediatric center (average of 3.6 transplants per year), which showed an increase in the number of transplants in the last few years (more than 5 OHT/year in the last decade). Despite the lower number of transplants, we had a high early survival rate (94.4%). The overall survival is influenced by the volume of transplants performed in the centers, according to the ISHLT, with the larger mortality in smaller centers (< 4 pediatric heart transplants performed per year).⁵ Our early mortality was similar to the data from national and international studies [5, 17, 37, 38].

In contrast with the Twenty-fourth pediatric heart transplantation report (2021) that showed better survival in patients below 10 years of age and in patients with primary diagnosis of CMP, we found no difference in late survival among patients of different age groups, as well as among patients with CMP or CHD and this is probably due to the small sample size [5].

This paper has some limitations: (1) this is a single center study with a small number of patients; (2) some data from early patients were not available.

Heart transplant is an acceptable therapeutic option for children and young adults, even in small centers with outcomes comparable to large centers. While there may be challenges in resource-limited settings, it is still possible to achieve good long-term outcomes for children with life-threatening heart disease.

Contributors

All authors contributed to the study conception and design. CTMBC, KMPCB, ICLM, IBP, ACOT, and RSASO performed material preparation, data collection and analysis. The first draft of the manuscript was written by CTMBC, KMPCB, ICLM, MBC, and RGP and all authors commented on previous versions of the manuscript. CTMBC, KMPCB, ICLM, MBC, VCPJ, and RGP contributed reviewing and editing the final version. All authors read and approved the final manuscript.

Data sharing statement

Data can be provided by corresponding author upon request.

Declaration of interests

Authors report no conflicts of interest

Funding:

No funding

Author Contribution

Author's contributionC. T.M.B.C: conceptualization, study design, data collection, data analysis, data interpretation, supervision, creation of figures and images, writing (original draft)V.C.P.J: conceptualization, study design, data analysis, data interpretation, supervision, writing (review).R.G.P: conceptualization, study design, data analysis, data interpretation, supervision, writing. g (review)I.C.L.M: conceptualization, study design, data collection, data analysis, data interpretation, supervision, writing (review)I.B.P: conceptualization, study design, data collection, data analysis, data interpretation, supervision, writing (review)A. C.O.T: conceptualization, study design, data collection, data analysis, data interpretation, supervision, writing (original draft)R.S.A.S.O: conceptualization, study design, data analysis, data interpretation, supervision, writing (review).T.C: data analysis, data interpretation, supervision, writing (review).S.C.M.S: data analysis, data interpretation, supervision, writing (review).K.M.P.C.B: conceptualization, study design, data analysis, data interpretation, supervision, writing (review).

Acknowledgements

We would like to acknowledge the Edson Queiroz Foundation/University of Fortaleza for their publishing fee support.

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Clinical outcome of heart transplantation in children and young adults with congenital and acquired heart disease in a middle-income country: a 20-year single-center experience

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Abstract

Background

Methods

Results

Conclusion

Figures

Introduction

Methods

Surgical techniques

Immunosuppression

Follow up

Statistical analysis

Results

Patient population

Number of Transplantations

Circulatory support

Immunosuppressive therapy

Follow up and complications

Graft vascular disease and lymphoproliferative disease

Renal dysfunction

Re-transplants

Overall survival

Interpretation

Infections and rejections

Renal dysfunction

Re-transplantation

Circulatory Support

Early and late mortality

Conclusion

Declarations

Contributors

Data sharing statement

Declaration of interests

Funding:

Author Contribution

Acknowledgements

References

Additional Declarations

Status:

Version 1