Anusha Konduri

The Fontan procedure provides long-term palliation for patients with single-ventricle physiology, but long-term outcomes remain limited by progressive Fontan circulatory failure. Early identification of patients at risk for adverse outcomes is critical to guide surveillance and management strategies. We aimed to identify peri-Fontan factors associated with mortality or need for advanced cardiac therapies in Fontan patients. We conducted a retrospective matched case-control study of patients who underwent Fontan completion between 2000 and 2023 at a single tertiary congenital heart center. Cases were defined as patients who experienced death, ventricular assist device (VAD) implantation, or heart transplantation after Fontan completion. Each case was matched with three controls by year of Fontan surgery and duration of follow-up. Pre-Fontan hemodynamics, cardiac anatomy, and perioperative variables were analyzed using conditional logistic regression. A total of 53 cases who experienced death, VAD implantation, or heart transplantation were matched to 151 controls. The median age at Fontan failure was 11.5 years (IQR 6.9-16.1), occurring a median of 8.6 years (IQR 3.8-13.8) after Fontan completion. In multivariable analysis, the factors independently associated with death/transplant/VAD implantation were systemic right ventricular morphology (adjusted odds ratio [aOR] 6.87, 95% CI 2.07-22.8, p = 0.002), pre-Fontan Glenn/hemi-Fontan pressure > 12 mmHg (aOR 4.72, 95% CI 1.74-12.8, p = 0.002), and postoperative hospital length of stay > 12 days (aOR 8.57, 95% CI 2.78-26.4; p = 0.0002). Systemic right ventricular morphology, elevated pre-Fontan Glenn/hemi-Fontan pressure, and prolonged postoperative hospitalization are independently associated with long-term mortality or need for advanced cardiac therapies after Fontan completion. These findings add to the growing body of literature identifying peri-Fontan factors associated with adverse long-term outcomes and support the importance of perioperative hemodynamics and postoperative recovery in long-term Fontan risk assessment.

Background: Antibody‐mediated rejection (AMR) remains a significant complication following heart transplantation, contributing to graft dysfunction and reduced survival. Donor‐derived cell‐free DNA (dd‐cfDNA) is emerging as a non‐invasive biomarker for detecting and monitoring graft injury, correlating with episodes of rejection and response to treatment. Daratumumab, an anti‐CD38 monoclonal antibody targeting plasma cells, has shown promise in treating AMR. We present a case series of pediatric and young adult heart transplant recipients demonstrating donor‐derived cell‐free DNA's potential utility in monitoring for AMR and the effect of therapies including daratumumab. Case Descriptions: We report five cases showing that elevated dd‐cfDNA correlated with pathological AMR (pAMR), and treatment with daratumumab improved both pAMR and dd‐cfDNA levels. Most of our patients had persistently elevated donor‐specific antibody (DSA) as observed by MFI values; however, there was a reduction in DSA titer that corresponded with improvement in pAMR and dd‐cfDNA levels. Recurrent increases in dd‐cfDNA were also useful in guiding the need for repeat treatment with daratumumab. Although DSA levels often remained elevated despite histologic improvement, decreasing dd‐cfDNA levels correlated more closely with the resolution of AMR. Conclusion: In this case series of pediatric and young adult heart transplant recipients, our findings suggest that dd‐cfDNA can serve as a valuable biomarker for diagnosing AMR and treatment response, which are not often reflected by DSA MFI alone. Our dd‐cfDNA data supports the efficacy of daratumumab in treating AMR and may guide the need for ongoing treatment. Further studies are warranted to validate these findings and establish guidance for the use of daratumumab and dd‐cfDNA in this patient population.

Background: Elevated pulmonary vascular resistance is a significant risk factor for right‐ventricle failure and poor outcomes following pediatric heart transplantation. Pulmonary vasodilator therapy can help manage symptoms and improve heart transplant candidacy. While phosphodiesterase type 5 inhibitors and endothelin receptor antagonists are commonly used, prostacyclin therapy remains less studied in this context. Case Description: A 15‐year‐old female with Shone's complex developed heart failure with preserved ejection fraction and severe pulmonary hypertension. Given her indexed pulmonary vascular resistance (15 indexed wood units with vasodilator testing) on initial cardiac catheterizations was felt to be prohibitive to heart transplant, she was treated stepwise with tadalafil, ambrisentan, and selexipag. Serial cardiac catheterizations showed an improvement in her pulmonary vascular resistance as well as vasoreactivity of her pulmonary vasculature. She was listed for heart transplant and underwent transplantation with perioperative support including inhaled prostacyclin. Post‐operatively, her mean pulmonary artery pressure and pulmonary vascular resistance improved, though she later required a transition to subcutaneous treprostinil for recurrence of pulmonary hypertension with right‐ventricle failure despite only a mildly elevated left ventricle end‐diastolic pressure. Over the following year, her pulmonary pressures stabilized, and she was transitioned back to oral therapies and continued to do well at 1 year post‐transplantation. Conclusion: This case highlights that aggressive medical management, including prostacyclin therapy, can render even high‐risk pediatric patients with elevated pulmonary vascular resistance eligible for heart transplant and improve post‐operative outcomes. It supports emerging evidence that elevated pulmonary vascular resistance, particularly when responsive to vasodilators, should not be viewed as an absolute contraindication to heart transplantation and emphasizes the importance of tailored, ongoing pulmonary hypertension management in children with congenital heart disease.

Heart failure is a significant cause of morbidity and mortality in patients with congenital heart disease (CHD). While clinical guidelines for acquired cardiovascular diseases exist, evidence-based therapies for heart failure in CHD are lacking. Angiotensin II receptor blocker and neprilysin inhibitor (ARNI) therapy has shown efficacy in adults with heart failure, reducing cardiovascular mortality and hospitalizations, but its use in pediatric CHD patients remains underexplored. This study aimed to evaluate the safety and efficacy of Sacubitril/Valsartan (ARNI) in pediatric and young adult patients with CHD. We conducted a retrospective chart review of 29 patients who received ARNI therapy between August 2021 and December 2023. The patients’ age ranged from 5.3 months to 22.8 years. Fifteen of the 29 patients (52%) had single ventricle CHD. The median time for follow-up since ARNI initiation was 8 months (range 6 days–2.4 years). Twelve (41%) patients experienced hypotension which necessitated dose adjustments, temporary withholding of the medication, or discontinuation. Additionally, 2 patients developed acute kidney injury. The medication had to be discontinued in 7 patients (24%) due to hypotension (3 or 10%), AKI (2 or 7%) and progression of heart failure needing advanced cardiac therapies (2 or 7%). A comparative analysis of clinical and laboratory data before and after ARNI therapy revealed a significant reduction in systolic blood pressure ( p = 0.01), as well as increases in serum creatinine and potassium levels ( p = 0.02 and p = 0.03, respectively). Additionally, there was a trend toward improvement in ventricular systolic function observed on echocardiogram after ARNI therapy; however, this was in the context of patients receiving concomitant other oral heart failure medications. Our findings highlight the need for careful monitoring and individualized management of ARNI therapy in pediatric CHD patients. Larger, well-designed trials are essential to establish clear treatment guidelines and optimize the use of ARNI therapy in this population.

Heart failure is the leading cause of morbidity and mortality in patients with Fontan circulation. Sodium-glucose-cotransporter 2 inhibitors (SGLT2i) have become a mainstay of heart failure therapy in adult patients, however, there remains a paucity of literature to describe its use in pediatric heart failure patients, especially those with single ventricle physiology. We describe our early experience using SGLT2i in patients with single ventricle congenital heart disease surgically palliated to the Fontan circulation. We conducted a single-center retrospective chart review of all patients with Fontan circulation who were initiated on an SGLT2i from January 1, 2022 to March 1, 2023. Patient demographics, diagnoses, clinical status, and other therapies were collected from the electronic medical record. During the study period, 14 patients (median age 14.5 years, range 2.0-26.4 years) with Fontan circulation were started on a SGLT2i. Mean weight was 54 kg (range 11.6–80.4 kg). Median follow-up since SGLT2i initiation was 4.1 months (range 13 days-7.7 months). Four patients had a systemic left ventricle and 10 had a systemic right ventricle. Half the patients had Fontan Circulatory Failure with reduced Ejection Fraction (FCFrEF) of the systemic ventricle and the other half had Fontan Circulatory Failure with preserved Ejection Fraction (FCFpEF) of the systemic ventricle. In addition, 3 patients experienced Protein Losing Enteropathy (PLE) and 2 patients had plastic bronchitis, one of whom also was diagnosed with chylothorax. There were no genitourinary infections, hypoglycemia, ketoacidosis, hypotension or other significant adverse effects noted in our patient population. One patient experienced significant diuresis and transient acute kidney injury. Patients with FCFrEF showed a decrease in natriuretic peptide levels. Given the lack of proven therapies, demonstrated benefits of SGLT2i in other populations, and some suggestion of efficacy in Fontan circulation, further study of SGTLT2i in patients with Fontan circulation is warranted.

Two standard surgical palliative options for neonates born with pulmonary atresia and intact ventricular septum (PA/IVS) include uni-or biventricular repair. Whenever feasible, the biventricular repair is considered to have better exercise capacity (XC) and outcomes. However, there is a paucity of data comparing objective XC between these two surgical techniques. Our aim was to compare XC, including longitudinal changes in patients with PA/IVS following uni-biventricular repair. We performed a single-center retrospective study of survivors with repaired PA/IVS who underwent comprehensive treadmill cardiopulmonary exercise testing. Initial and latest exercise parameters were compared for longitudinal analysis. Demographic and exercise parameters were collated. Peak oxygen uptake (VO₂ in ml/kg/min), an indicator of maximal aerobic capacity, peak heart rate, and other measures of spirometry performed at the same time were collected. Recorded parameters included, (a) Percentage of predicted VO₂ (% VO2) normalized for age, weight, height, and gender, (b) % oxygen (O₂) pulse, (c) anaerobic threshold (AT), (d) Chronotropic index (CI), (e) % Breathing reserve, (f) Forced vital capacity (FVC), (g) % Forced Expiratory volume in 1 s (FEV1), (h) Maximum voluntary ventilation (MVV), and (i) VE/VCO₂. Appropriate statistical tests were performed, and a p value < 0.05 was considered significant. A total of 35 patients (43% male, 57% univentricular repair) were included, with a mean (SD) age of 20.1(7.5) years. Patients with univentricular palliation demonstrated significantly impaired peak heart rate, chronotropic index (0.50 ± 0.2 vs. 0.90 ± 0.1, p = 0.02), VE/VCO₂ (35.4 ± 5.0 vs. 30.2 ± 2.8, p = 0.001), and %FVC (78.3 ± 8.3 vs. 88.6 ± 15.1, p = 0.02). There was a trend towards reduction in % VO₂ in the Fontan patients though it was statistically similar between the groups (68.4 ± 21.4 vs. 81.2 ± 18.9, p = 0.07). Longitudinal data were available for 11 patients in each group, and there was no longitudinal decline in their exercise parameters over similar intermediate follow-up duration [6.8 (UV) vs. 5.3 (BV) years]. We conclude that young survivors with PA/IVS with prior univentricular palliation demonstrated an objective impairment in their chronotropic parameters compared with the biventricular repair. However, this did not translate into a significant difference in their exercise capacity. There was no longitudinal decline in exercise capacity or other parameters over intermediate follow-up.

Background Two standard surgical palliative options for neonates born with pulmonary atresia and intact ventricular septum (PA/IVS) include uni-or biventricular repair. Whenever feasible, the biventricular repair is considered to have better exercise capacity (XC) and outcomes. However, there is a paucity of data comparing objective XC between these two surgical techniques. Objective To compare XC, including longitudinal changes in patients with PA/IVS following uni-biventricular repair. Methods This is a single-center retrospective study of survivors with repaired PA/IVS who underwent comprehensive treadmill cardiopulmonary exercise testing. Initial and latest exercise parameters were compared for longitudinal analysis. Patients with 1.5 ventricular repair, pacemaker, or incomplete data were excluded. Demographic and exercise parameters were collated. Peak oxygen uptake (VO₂ in ml/kg/min), an indicator of maximal aerobic capacity, peak heart rate, and other measures of spirometry performed at the same time were collected. Recorded parameters included, a) Percentage of predicted VO₂ (%VO₂) normalized for age, weight, height, and gender, b) % oxygen (O₂) pulse, c) anaerobic threshold (AT), d) Chronotropic Index (CI), e) % Breathing reserve, f) Forced Vital capacity (FVC), g) % Forced Expiratory Volume in 1 second (FEV1), and h) Maximum voluntary ventilation (MVV). Appropriate statistical tests were performed, and a p-value < 0.05 was considered significant. Results Thirty-five patients (43% male, 57% univentricular repair) underwent the latest exercise stress test at a mean (SD) age of 20.1 ± 7.5 years. There were no statistical differences in baseline demographic/clinical parameters between the two groups (univentricular (n = 20) vs. biventricular repair (n = 15)). Patients with univentricular palliation demonstrated significantly lower peak heart rate, chronotropic index (0.50 ± 0.2 vs. 0.90 ± 0.1, p = 0.02), and %FVC (78.3 ± 8.3 vs. 88.6 ± 15.1, p = 0.02). The % VO₂ was similar between the groups (68.4 ± 21.4 vs. 81.2 ± 18.9, p = 0.07). Longitudinal data was available for 11 patients in each group, and there was no longitudinal decline in their exercise parameters over similar intermediate follow-up duration (6.8 (UV) vs. 5.3 (BV) years). Conclusions Young survivors with PA/IVS with prior univentricular palliation demonstrated an objective impairment in their chronotropic parameters compared with the biventricular repair. However, this did not translate into a significant difference in their exercise capacity. There was no longitudinal decline in exercise capacity or other parameters over intermediate follow-up.

Background: DCM has rarely been reported in children with CD, but is a recognized complication in adults. DCM with uncontrolled heart failure may need heart transplantation, which could be challenging in CD.Case Description: We present a 9‐year‐old female with CD who was diagnosed with DCM and a measured Ejection fraction ~25.8%. She was initiated on heart failure treatment, but continued to have progressive symptoms and underwent bicaval OHT three months after her initial presentation. Her post‐operative course was complicated by perforation of the rectosigmoid junction requiring exploratory laparotomy and primary repair of the perforation. This was believed to be secondary to her underlying CD and possibly reperfusion injury after heart transplant. During the first‐year post heart transplant, she had 4 episodes of acute cellular rejection. These episodes were treated with high dose steroids with good results. The patient has been in remission from CD since transplantation. For the last two years she is doing well, with no further rejection episodes on current immunosuppression.Conclusion: DCM, though rare, can occur in patients with CD, whether active or in remission. The development of DCM could be insidious and keeping a high index of suspicion is important and subtle signs suggestive of cardiac involvement should warrant further investigation. The post‐transplant management can be challenging with early morbidity in the first post‐transplant year but overall good median survival and quality of life for our patient to date.