Heart Transplantation after Univentricular Palliation: Improved Outcomes and Increased Complexity.

AIM: Heart transplantation (HT) in patients with failing univentricular circulation is often challenging. This is compounded by the ever-increasing number of patients with prior Norwood-type reconstruction of the aorta, large aortic root, and often dense adhesions from multiple prior operations. We aimed to elucidate differences in outcomes of HT in patients with prior univentricular palliations, with and without prior Norwood-type aortic arch reconstruction (ArchRec). METHODS: All patients who underwent HT for failed univentricular palliation during the 1990-2022 period were included in the study. RESULTS: Of 45 patients, 18 had undergone ArchRec. Hospital mortality improved in the recent era (17.4% before 2006 vs 0% after 2006; p=0.11), despite a higher proportion of patients with ArchRec (17.4% before 2006 vs 60.8% after 2006, p=0.002). Patients with ArchRec had a higher number of prior cardiac surgeries (4.1±1.5 vs 3.2±1.3, p=0.04), longer cardiopulmonary bypass time (320±23 vs 242±21 min, p=0.02), more concomitant arch reconstruction (33.3% vs 0%, p=0.02), greater need for post-HT extracorporeal membrane oxygenation (33.3% vs 3.7%; p=0.01) and longer hospital stay (37.1±30.5 days vs 23.6±11.8 days, p=0.04). Freedom from death or retransplantation for all patients was 91%, 73%, 67%, and 53% at 1, 5, 10, and 15-years, respectively. Prior ArchRec, Fontan procedure, and earlier eras were not risk factors for death. CONCLUSIONS: The outcomes of HT after univentricular palliation have improved in recent times and low operative mortality can be achieved. Despite increased complexity, good similar outcomes can be achieved in patients with and without prior arch reconstruction regardless of the palliation stage.

Outcomes of extracardiac Fontan operation: A single institution experience with 398 patients.

OBJECTIVE: The study objective was to evaluate the outcomes of the extracardiac Fontan operation at a single institution. METHODS: We conducted a retrospective study of 398 patients from a single institution who underwent their initial extracardiac Fontan operation between 1997 and 2020. We determined the incidence of and risk factors for failure of the Fontan circulation, which includes death, Fontan takedown, heart transplantation, protein-losing enteropathy, plastic bronchitis, and functional status at the last follow-up. RESULTS: The median follow-up time was 10.3 years (interquartile range, 6.4-14.6). The overall survival was 96% and 86% at 10 and 20 years after extracardiac Fontan operation, respectively. There were 6 early deaths (6/398, 1.5%) and 15 late deaths (15/398, 3.8%). Forty-nine patients (12.5%) developed failure of the Fontan circulation. Freedom from the failure of Fontan circulation was 88% at 10 years and 76% at 20 years. Risk factors for failure of the Fontan circulation were right ventricular dominance (hazard ratio, 4.7; P < .001; 95% CI, 2.1-10.5), aortic atresia (hazard ratio, 5.5; P < .001; 95% CI, 2.3-12.8), and elevated mean pulmonary artery pressure (hazard ratio, 2.3; P = .002; 95% CI, 1.2-6.7). CONCLUSIONS: Rates of failure of the Fontan circulation are low after the contemporary extracardiac Fontan operation. Risk factors for failure of the extracardiac Fontan circulation include right ventricular dominance, aortic atresia, and elevated pulmonary artery pressures.

Long-Term Outcomes of Mechanical Aortic Valve Replacement in Children.

When the options of aortic valve repair or the Ross procedure are not feasible or have been exhausted, mechanical aortic valve replacement (AVR) may provide a reliable and structurally durable alternative, but with the limitations of long-term anticoagulation, thrombosis risk and lack of valve growth potential. In this article, we review the longitudinal outcomes of mechanical AVR in children in our institution and compare them to those recently reported by others. From 1978 to 2020, 62 patients underwent mechanical AVR at a median age of 12.4 years (interquartile range (IQR): 8.6-16.8 years). The most common underlying diagnoses were: conotruncal anomalies (40%, 25/62), congenital aortic stenosis (16%, 10/62), rheumatic valve disease (16%, 10/62), connective tissue disease (8.1%, 5/62) and infective endocarditis (6.5%, 4/62). Thirty-two patients (52%, 32/62) had at least 1 prior aortic valve surgery prior to mechanical AVR. Early death was 3.2% (2/62). Median follow-up was 14.4 years (IQR: 8.4-28.2 years). Kaplan-Meier survival was 96.8%, 91.9%, 86.3%, and 81.9% at 1, 5, 10, and 20 years. On competing risk analysis, the proportion of patients alive without aortic valve reoperation at 1, 5, 10, and 20 years was 95.2%, 87.0%, 75.5% and 55.4%, respectively, while the proportion of patients that had aortic valve reoperation (with death as a competing event) at 1, 5, 10, and 20 years was 1.6%, 4.9%, 12.8%, and 28.5%, respectively. In conclusion, when the options of aortic valve repair or the Ross procedure are not feasible in children, mechanical AVR is an alternative, yet the long-term rates of mortality and need for aortic valve reoperation are of concern.

Bex-Nikaidoh operation and the impact of double root translocation on outcomes.

OBJECTIVES: The Bex-Nikaidoh operation can effectively relieve left ventricular outflow tract obstruction. However, if a conduit is used for right ventricular outflow tract reconstruction, a late reoperation can be anticipated. We examined the impact of double root translocation on outcomes. METHODS: We performed a retrospective single-centre study of patients who underwent aortic root translocation between 2006 and 2019. RESULTS: Aortic root translocation was performed in 23 patients at a median age of 1.6 years [interquartile range (IQR) 0.9-2.5]. Concomitant repairs were done in 52.2% of patients (12/23) including the Senning atrial switch in 34.8% (8/23). The right ventricular outflow tract was reconstructed with valved conduits in 39.1% (9/23), direct anastomoses in 4.35% (1/23) and pulmonary autografts in 56.5% of patients (13/23). Aortic cross-clamp time was significantly longer in patients with double root translocation [308 min (IQR 270-259) vs 209 min (IQR 179-281), P = 0.02]; 2 patients in this group required temporary mechanical circulatory support. There were no early deaths. Median follow-up time was 7.5 years (IQR 3.3-10.5). The estimated 10-year survival was 90% [95% confidence interval (CI): 47.3%, 98.5%]. There was no recurrent left ventricular outflow tract obstruction. Freedom from any reoperation was 64.2% (95% CI: 40.8%, 80.3%) at 3 years and 44.5% (95% CI: 21.2%, 65.5%) at 6 years. The main indication for late reoperation was conduit degeneration. Freedom from a right ventricular outflow tract reoperation was significantly higher, and the number of reoperations per patient was lower when a double root translocation had been performed (P = 0.03). CONCLUSIONS: The Bex-Nikaidoh operation effectively relieved left ventricular outflow tract obstruction. A double root translocation further increased procedural complexity but was associated with better mid-term freedom from a right ventricular outflow tract reoperation. It should be considered in suitable patients.

Long-term outcomes of tetralogy of Fallot repair: A 30-year experience with 960 patients.

OBJECTIVE: This study evaluates the long-term results of tetralogy of Fallot repair and assesses the risk factors for adverse outcomes. METHODS: This retrospective study included 960 patients who underwent transatrial transpulmonary tetralogy of Fallot repair between 1990 and 2020. RESULTS: A transannular patch was placed in 722 patients, and pulmonary valve preservation was achieved in 233 patients. The median age at tetralogy of Fallot repair was 9.4 (interquartile range, 6.2-14.2) months. The median follow-up duration was 10.6 (interquartile range, 5.4-16.3) years. There were 8 early deaths (0.8%) and 20 late deaths (2.1%). Genetic syndrome and pulmonary valve annulus Z score less than -3 were risk factors for mortality. The survival was 97.7% (95% confidence interval, 96.4-98.5) and 94.5% (95% confidence interval, 90.9-96.7) at 10 and 30 years, respectively. Freedom from any reoperation was 86.4% (95% confidence interval, 83.6-88.7) and 65.4% (95% confidence interval, 59.8-70.4) at 10 and 20 years, respectively. Postoperative right ventricular outflow tract peak gradient of 25 mm Hg or greater correlated with reoperation. Propensity score-matched analysis demonstrated that freedom from pulmonary valve replacement at 15 years was higher in the pulmonary valve preservation group compared with the transannular patch group (98.2% vs 78.4%, P = .004). Freedom from reoperation for right ventricular outflow tract obstruction at 15 years was lower in the pulmonary valve preservation group compared with the transannular patch group (P = .006). CONCLUSIONS: The long-term outcomes of tetralogy of Fallot repair are excellent. A postoperative right ventricular outflow tract peak gradient less than 25 mm Hg appears to be optimal to prevent reoperation. If the pulmonary valve size is suitable, pulmonary valve preservation reduces the risk of pulmonary valve replacement, yet increases the reoperation rate for right ventricular outflow tract obstruction.

Truncal valve repair in an adolescent with severe annular dilatation.

Approximately 20% of patients with truncus arteriosus might need a truncal valve procedure within 20 years after anatomical repair due to regurgitation. These patients commonly develop valve regurgitation due to root dilatation with a sufficient amount of good quality valvular tissue. Thus, the reduction of the truncal annulus is the single most important factor to achieve durable repair, especially in patients in whom the Ross procedure is not an option.

T-Remodeling of the Pulmonary Artery Bifurcation for Pulmonary Artery Origin Stenosis.

BACKGROUND: Various surgical techniques are utilized for reconstructing hypoplastic pulmonary arteries (PAs) in patients with conotruncal anomalies and at times, may be susceptible to restenosis and reoperation. We reviewed our experience with a simple technique of T-shaped remodeling of the PA bifurcation. METHODS: Between 2005 and 2019, 31 patients underwent T-remodeling of central PAs by a single cardiac surgeon. The PA bifurcation was opened cranially, and the opening was augmented with an oval-shaped patch effectively transforming the V-shaped bifurcation into a T-shaped bifurcation. Both origins of the PAs were enlarged, even in the instance of single PA origin stenosis. RESULTS: Median age at time of T-remodeling was 17 months (range: 7 weeks to 14 years). The following cardiac morphologies were observed: tetralogy of Fallot (n = 12, 39%), pulmonary atresia with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (n = 8, 26%), truncus arteriosus (n = 6, 19%), pulmonary atresia with VSD (n = 3, 9.7%), and transposition of the great arteries (n = 2, 6.5%). Thirteen patients (42%) had previous central shunt, and eight patients (26%) had previous modified Blalock-Taussig shunt. There were no operative mortalities. Immediately after T-remodeling, echocardiographic estimates of right ventricle to PA gradient decreased from 42 [interquartile range 28-58] mm Hg to 20 [12-36] mm Hg (P = .03). Freedom from reoperation on the PA bifurcation for the entire cohort was 100% at one year, 88% (95% CI 68%-96%) at five years and 82% (57%-93%) at ten years. CONCLUSIONS: T-remodeling for PA origin stenosis is a safe procedure with excellent freedom from reoperation that is easily reproducible and applicable to patients with all cardiac morphologies.

Aortic valve repair in a low-birth-weight neonate with poor ventricular function: staged tricuspidization of the unicuspid valve.

Congenital severe isolated aortic stenosis in neonates requires prompt intervention because left ventricular function may deteriorate rapidly. Surgical repair of a stenotic aortic valve in neonates allows debridement of fibrous material and precision commissurotomy. As such, the child would end up with a much better-quality aortic valve compared to the uncontrolled tear that results following balloon dilatation. The meticulous debridement and precise commissurotomy are important in achieving long-term durability of the aortic valve repair, with the expectation that the patient may keep the native aortic valve at least into adolescence or adulthood. If feasible, it is important to avoid placement of patches while repairing the valve, so that the growth potential of the cusps is preserved. The valve could be revisited and repaired further, so that, ideally, the native valve could be retained for life, thus avoiding aortic valve replacement entirely. We present a low-birth-weight neonate with a dysplastic unicuspid aortic valve, severe aortic valve stenosis and decreased left ventricular function who underwent repair of the aortic valve.

Aortic valve-sparing procedure in the pediatric population.

Background: Aortic valve-sparing procedures have been established as a mainstream treatment option for adult patients with aortic root aneurysms. However, data regarding their use in the pediatric population is limited. This study reports on our experience with aortic valve-sparing procedures in children. Methods: A retrospective review was conducted of all patients who underwent an aortic valve-sparing procedure at the Royal Children's Hospital, Melbourne, Australia between April 2006 and April 2016. Clinical and echocardiographic data were analyzed. Results: The study included 17 patients, with a median age of 15.7 years and a majority of patients being male (82.4%). The most common diagnosis was transposition of great arteries after arterial switch operation, followed by Loeys-Dietz syndrome and Marfan syndrome. Preoperative echocardiography showed more than moderate aortic regurgitation in 94.1% of the patients. The David procedure was performed in all 17 patients, with no mortality during follow-up. Reoperation was required in 29.4% of patients, and 23.5% required aortic valve replacement. Freedom from reoperation for aortic valve replacement at 1, 5, and 10 years was 93.8%, 93.8% and 68.2% respectively. Conclusions: Aortic valve-sparing surgery can be successfully performed in the pediatric population. However, it requires a highly skilled surgeon due to the often dysplastic or distorted nature of these valves and the need for additional procedures on the aortic valve leaflets.

The Ross Procedure in Children: Defining the Optimal Age.

BACKGROUND: It has been proposed that delaying the Ross procedure to later in childhood, allowing autograft stabilisation and placement of a larger pulmonary conduit, may improve outcomes. However, the effect of age at the time of Ross procedure on outcomes remains unclear. METHODS: All patients who underwent the Ross procedure between 1995 and 2018 were included in the study. Patients were divided into four groups: infants, age 1 to 5 years, age 5 to 10 years and age 10 to 18 years. RESULTS: A total of 140 patients underwent the Ross procedure in the study period. Early mortality was 23.3% (7/30) for infants compared to 0% for older children (p<0.001). Survival at 15 years was significantly lower in infants (76.3%±9.9%), compared to children aged 1 to 5 years (90.9%±20.1%), 5 to 10 years (94%±13.3%), and 10 to 18 years (86.7%±10.0%), p=0.01. Freedom from autograft reoperation at 15 years was significantly lower in infants (58.4%±16.2%), compared to children aged 1 to 5 years (77.1%±14.9%), 5 to 10 years (84.2%±6.0%) and 10 to 18 years (87.8%±9.0%), p=0.01. Overall freedom from reoperation at 15 years was 13.0%±6.0% for infants, 24.2%±9.0% for children aged 1 to 5 years, 46.7%±15.8% for children aged 5 to 10 years, and 78.4%±10.4%, p<0.001. CONCLUSIONS: The Ross procedure performed after 10 years of age appears to be associated with improved freedom from reoperation, primarily due to a reduction in reoperation on the pulmonary conduit.

Outcomes of Mitral Valve Repair in Children With Infective Endocarditis: A Single-Center Experience.

Mitral valve infective endocarditis (IE) in children is rare, and there are few reports on the outcomes of surgery in these patients. This study investigated the long-term outcomes of mitral valve repair in children with IE. Data were retrospectively obtained from medical records and correspondence. Univariable regression analyses were performed and outcomes including survival and freedom from reoperation were analyzed using the Kaplan-Meier method. Surgery for native mitral valve IE was performed in 39 patients between 1987 and 2020. Of these, 92.3% (36/39) of patients underwent mitral valve repair, while 7.7% (3/39) required replacement. Median age was 8 years. Preoperatively, 80.5% (29/36) of patients had moderate or greater mitral regurgitation. Congenital heart disease was present in 38.9% (14/36), while 11.1% (4/36) had rheumatic heart disease and 25.0% (9/36) had prior cardiac surgery. Postoperatively, only 1 patient (2.8%, 1/36) had moderate or greater residual mitral regurgitation. There were 2 early deaths (5.6%, 2/36), with survival being 94.1% (95%CI, 78.5-98.5) at 15 years. At 10 years, freedom from reoperation was 62.9% (95%CI, 41.0-78.5) while freedom from mitral valve replacement was 80.2% (95%CI, 55.5-92.3). Larger vegetation size was a risk factor for embolic events both pre- and postoperatively (OR, 1.15, P = 0.02). Mitral valve repair is feasible in the majority of children requiring surgery for mitral valve IE. Survival is excellent, and at 10 years, approximately two-thirds of patients are free from mitral reoperation, and 80% are free from replacement. Larger vegetation size is associated with an increased risk of embolic events.

Long-term Outcomes of Transatrial-Transpulmonary Repair of Tetralogy of Fallot With Anomalous Coronary Arteries.

Repair of tetralogy of Fallot (TOF) can be complicated by the presence of an anomalous coronary artery (ACA) crossing the right ventricular outflow tract (RVOT). This study sought to evaluate the late outcomes of a policy of transatrial-transpulmonary repair for this condition. The transatrial-transpulmonary approach was used in 864 consecutive TOF repairs between 1993 and 2018 at a single institution, of which 55 (6%) patients had an ACA. Nineteen (35%,19/55) patients underwent prior palliation. Late survival and freedom from reoperations were compared with the general cohort of 809 patients who underwent complete repair during the same period. Early mortality was 2% (1/55). Median follow-up was 15.6 years. Late mortality was 6% (3/54). Absence of a preoperative diagnosis of ACA was not a risk factor for worse outcomes in terms of late re-interventions, acute coronary syndrome, residual RVOT gradient, and late mortality. Survival was 91% (95% confidence interval [CI]: 77-96%) at 20 years and was comparable to the general TOF cohort (95%, 95% CI: 90-98%, P = 0.12). Actuarial freedom from any re-intervention was 46% (95% CI: 27-62%) at 20 years, which was also comparable to the general cohort (31%, 95% CI: 20-42%, P = 0.19). The presence of an ACA does not appear to affect late survival or re-intervention rates in patients undergoing transatrial-transpulmonary repair of TOF.

Kawashima Procedure: The Impact of Age.

BACKGROUND: The results of the Kawashima operation are incompletely defined. Furthermore, optimal timing of Kawashima operation, an important consideration when managing desaturated young infants awaiting surgery, remains unclear. We reviewed our outcomes of Kawashima operation, with a focus on the impact of age. METHODS: We conducted a retrospective review of patients who underwent Kawashima operation from 1990 to 2020. RESULTS: Thirty patients underwent Kawashima operation at a median age of 11.7 months (interquartile range, 4.4-27.4). Left isomerism was present in 27 patients (90%). There were no early deaths. There were 2 patients (6.7%) who had Kawashima takedown, both attributed to hypoxia. Fontan completion was achieved in 25 patients (83%). Overall freedom from death and transplantation at 20 years was 67% (95% CI, 32%-87%). Freedom from death and transplantation at 10 years was 100% for children 3 to 6 months of age at the time of Kawashima, compared with 86.4% for older children (P = 1.0). However, children aged 3 to 6 months had longer ventilation time (P = .01), intensive care stays (P = .03), and hospital stays (P = .05). Freedom from death or transplantation at 20 years among those who had concomitant common atrioventricular valve repair was 33%, vs 79% for those who did not undergo common atrioventricular valve repair (P = .02). CONCLUSIONS: Kawashima operation can be performed with low operative risk and acceptable long-term outcomes. Performing Kawashima operation on a patient aged less than 6 months does not affect survival, but is associated with increased morbidity. Need for common atrioventricular valve operation carries significant risk of mortality, and more effective techniques for atrioventricular valve repair are required.

Surgery for paravalvular abscess in children.

Objective: To investigate the outcomes of surgery in children with paravalvular abscess at our institution. Methods: A retrospective review of all patients who underwent surgery for paravalvular abscess was performed. Results: Between 1989 and 2020, 30 patients underwent surgery for paravalvular abscess, of whom 5 (16.7%) had an intracardiac fistula and 6 (20.0%) had a pseudoaneurysm. Aortic annulus abscesses were most common, occurring in 23 patients (76.7%). Aortic root replacement was performed in 17 patients (56.7%), root reconstruction was performed in 4 (13.3%), and reconstruction of the central fibrous body was required in 5 (16.7%). Postoperatively, 7 patients (23.3%) required extracorporeal membrane oxygenation (ECMO) support, and 1 patient (3.3%) required permanent pacemaker insertion. There were 6 early deaths, 5 of whom were on ECMO, and no late deaths, with a 15-year survival of 79.7% (95% confidence interval [CI], 60.2%-90.3%). Deaths were from sudden cardiac arrest resulting in brain death in 3 patients, inability to wean from ECMO due to severe cardiac dysfunction in 2 patients, and cerebral mycotic aneurysm and hemorrhage in 1 patient. Freedom from reoperation was 40.0% (95% CI, 17.0%-62.3%) at 15 years Reoperation due to recurrence was rare, occurring in only 2 patients (6.7%). Streptococcus pneumoniae (hazard ratio [HR], 9.2; 95% CI, 1.6-51.7) and preoperative shock (HR, 6.4; 95% CI, 1.3-32.0) were associated with mortality. Central fibrous body reconstruction was associated with reoperation (HR, 4.4; 95% CI, 1.2-16.1). Conclusions: Although paravalvular abscess in children is associated with high early mortality, hospital survivors have good long-term survival. Reoperation is frequent, but is rarely due to recurrence of endocarditis.

Intrinsic activation of cardiosphere-derived cells enhances myocardial repair.

OBJECTIVE: Permanent loss of cardiomyocytes after myocardial infarction results in irreversible damage to cardiac function. The present study aims to enhance the cardiomyogenic efficiency of cardiosphere-derived cells (CDCs) to develop into large populations of cardiomyocytes by intrinsic activation of cardio-specific differentiation factors (Gata4, Mef2c, Nkx2-5, Hand2, and Tnnt2) by a CRISPR/dCas9 assisted transcriptional enhancement system. METHODS: Exhaustive screening was performed to identify the specific sequences in endogenous regulatory regions (enhancers and promoters) responsible for transcriptional activation of the target genes, via a CRISPR/dCas9 system fused with transcriptional activator VP64 (CRISPR-dCas9-VP64). In a rat model of acute myocardial infarction, we compared the regenerative potential and functional benefits of CDCs with or without transcriptional activation. RESULTS: We identified a panel of specific CRISPR RNA targeting the enhancers and promoters, which demonstrated significantly higher expression of differentiation factors of Gata4, Hand2, and Tnnt2. The group of CDCs with transcriptional activator VP64 (CDC with VP64) showed significant improvement in the left ventricular ejection fraction (61.9% vs 52.5% and 44.1% in the CDC without transcriptional activation group and control) and decreased scar area in the heart. CONCLUSIONS: We have identified endogenous regulatory regions responsible for an intrinsic activation of cardio-specific differentiation factors assisted via a CRISPR/dCas9 gene transcriptional system. The CRISPR/dCas9 system may provide an efficient and effective means of regulating Tnnt2 gene activation within stem cells. Subsequently, this system can be used to enhance transplanted CDCs differentiation potential within ischemic myocardia to better therapeutic outcomes of patients with ischemic heart disease.

Outcomes of total anomalous pulmonary venous drainage repair in neonates and the impact of pulmonary hypertension on survival.

Background: Mortality after repair of total anomalous pulmonary venous drainage (TAPVD) in neonates has remained high. Analysis of risk factors may help identify therapeutic targets to improve survival. Methods: Retrospective analysis of all neonates who underwent simple TAPVD repair. Results: Between 1973 and 2021, 175 neonates underwent TAPVD repair, at a median age of 6 days (interquartile range, 2-15 days) and a mean weight of 3.2 ± 0.6 kg. TAPVD was supracardiac in 42.3% of the patients (74 of 175), cardiac in 14.3% (25 of 175), infracardiac in 40% (70 of 175), and mixed type in 3.4% (6 of 175), with obstruction in 65.7% (115 of 175). Pulmonary hypertension (PHT) crisis occurred in 12% (21 of 175). Early mortality was 9.7% (17 of 175) and late mortality was 5.1% (8 of 158), with most deaths occurring within 1 year (75%; 6 of 8). Survival was 86.5% (95% CI, 80.3%-90.8%) at 1 year and 85.8% (95% CI, 79.6%-90.3%) at 5, 10, 15, and 20 years. Survival was lower in patients with obstructed TAPVD, patients with emergent surgery, and those with PHT crisis. PHT crisis (hazard ratio [HR], 4.93; 95% CI, 1.95-12.51; P = .001), urgency of surgery (HR, 2.51; 95% CI, 1.11-5.68; P = .027), and higher pulmonary artery pressure-to-systemic blood pressure percentage ratio (HR, 1.06; 95% CI, 1.01-1.11; P = .026) were identified as risk factors for mortality. Histopathological analysis of 17 patients (9.7%; 17 of 175) showed signs of pulmonary arterial hypertension with media hypertrophy in 58.8% (10 of 17). Conclusions: Mortality after TAPVD repair occurred mainly within the first year of life. Urgency of surgery and persistent PHT appears to be risk factors for mortality. Lung biopsy might be useful for identifying patients at risk and guiding newer treatment modalities.

Stem Cell Therapy in Heart Disease: Limitations and Future Possibilities.

Heart diseases are one of the major causes of morbidity and mortality worldwide. Despite major advances in drug and interventional therapies, surgical procedures, and organ transplantation, further research into new therapeutic options is still necessary. Stem cell therapy has emerged as one option for the treatment of a variety of heart diseases. Although a large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach, the results obtained from these clinical studies are inconsistent, and stem cell-based improvements of heart performance and cardiac remodeling were found to be quite limited. Since the precise mechanisms underlying the therapeutic actions of stem cells are still under debate, researchers have developed a variety of strategies to improve and boost the potency of stem cells in repair. In this Reviews, we summarize both the current therapeutic strategies using stem cells and future directions for enhancing stem cell potency.

An overview of stem cell therapy for paediatric heart failure.

Significant achievements in paediatric cardiology, surgical treatment and intensive care of congenital heart disease have drastically changed clinical outcomes for paediatric patients. Nevertheless, late-onset heart failure in children after staged surgeries still remains a serious concern in the medical community. Heart transplantation is an option for treatment; however, the shortage of available organs is a persistent problem in many developed countries. In order to resolve these issues, advanced technologies, such as innovative mechanical circulatory support devices and regenerative therapies, are strongly desired. Accumulated evidence regarding cell-based cardiac regenerative therapies has suggested their safety and efficacy in treating adult heart failure. Given that young children seem to have a higher regenerative capacity than adults, stem cell-based therapies appear a promising treatment option for paediatric heart failure as well. Based on the findings from past trials and studies, we present the potential of various different types of stem cells, ranging from bone marrow mononuclear cells to cardiosphere-derived stem cells for use in paediatric cell-based therapies. Here, we assess both the current challenges associated with cell-based therapies and novel strategies that may be implemented in the future to advance stem cell therapy in the paediatric population.