BACKGROUND: Observational studies have demonstrated an association between the use of digoxin and reduced interstage mortality after Norwood operation for hypoplastic left heart syndrome (HLHS). Digoxin use has increased significantly but remains variable between different hospitals, independent of case-mix. Instrumental variable analyses have the potential to overcome unmeasured confounding, the major limitation of previous observational studies and to generate an estimate of the attributable benefit of treatment with digoxin.

METHODS: A cohort of neonates with HLHS born from January 1, 2007 to December 31, 2021 who underwent Norwood operation at Pediatric Health Information Systems Database hospitals and survived >14 days after operation were studied. Using hospital-specific, 6-month likelihood of administering digoxin as an instrumental variable, analyses adjusting for both unmeasured confounding (using the instrumental variable) and measured confounders with multivariable logistic regression were performed.

RESULTS: The study population included 5,148 subjects treated at 47 hospitals of which 63% were male and 46% non-Hispanic white. Of these, 44% (n = 2,184) were prescribed digoxin. Treatment with digoxin was associated with superior 1-year transplant-free survival in unadjusted analyses (85% vs 82%, P = .02). This survival benefit persisted in an instrumental-variable analysis (OR: 0.71, 95% CI: 0.54-0.94, P = .01), which can be converted to an absolute risk reduction of 5% (number needed to treat of 20).

CONCLUSIONS: In this observational study of patients with HLHS after Norwood using instrumental variable techniques, a significant benefit in 1-year transplant-free survival attributable to digoxin was demonstrated. In the absence of clinical trial data, this should encourage the use of digoxin in this vulnerable population.

INTRODUCTION: Observational studies have demonstrated an association between use of digoxin and reduced interstage mortality after Norwood operation for hypoplastic left heart syndrome (HLHS). Digoxin use has increased significantly but remains variable between different hospitals, independent of case-mix. Instrumental variable analyses have the potential to overcome unmeasured confounding, the major limitation of previous observational studies and to generate an estimate of the attributable benefit of treatment with digoxin.

METHODS: A cohort of neonates with HLHS born from 1/1/2007 to 12/31/2021 who underwent Norwood operation at Pediatric Health Information Systems Database hospitals and survived >14 days after operation were studied. Using hospital-specific, 6-month likelihood of administering digoxin as an instrumental variable, analyses adjusting for both unmeasured confounding (using the instrumental variable) and measured confounders with multivariable logistic regression were performed.

RESULTS: The study population included 5,148 subjects treated at 47 hospitals of which 63% were male and 46% non-Hispanic white. Of these, 44% (n=2,184) were prescribed digoxin. Treatment with digoxin was associated with superior 1-year transplant-free survival in unadjusted analyses (85% vs. 82%, p=0.02). This survival benefit persisted in an instrumental-variable analysis (OR: 0.71, 95% CI: 0.54-0.94, p=0.01), which can be converted to an absolute risk reduction of 5% (number needed to treat of 20).

CONCLUSION: In this observational study of patients with HLHS after Norwood using instrumental variable techniques, a significant benefit in one-year transplant-free survival attributable to digoxin was demonstrated. In the absence of clinical trial data, this should encourage the use of digoxin in this vulnerable population.

<p><strong>BACKGROUND: </strong>Survivors of Fontan palliation are at life-long risk of thrombosis, arrhythmia, and circulatory failure. To our knowledge, no studies have evaluated current United States pharmaceutical prescription practice in this population.</p>

<p><strong>METHODS: </strong>A retrospective observational study evaluating the prevalent use of prescription medications in children and adolescents with hypoplastic left heart syndrome or tricuspid atresia after Fontan completion (identified using ICD9/10 codes) was performed using data contained in the MarketScan® Commercial and Medicaid databases for the years 2013 through 2018. Cardiac pharmaceuticals were divided by class. Anticoagulant agents other than platelet inhibitors, which are not uniformly a prescription medication, were also studied. Associations between increasing age and the likelihood of a filled prescription for each class of drug were evaluated. Annualized retail costs of pharmaceutical regimens were calculated.</p>

<p><strong>RESULTS: </strong>A cohort of 4056 subjects [median age 12 years (IQR: 8-16), 61% male, 60% commercial insurance] was identified. Of the cohort, 50% received no prescription medications. Angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (38%), diuretics (15%), and mineralocorticoid receptor antagonists (8%) were prescribed with the highest frequency. Pulmonary vasodilators were received by 6% of subjects. Older age was associated with increased likelihood of filled prescriptions for anticoagulants (p=0.008), antiarrhythmic agents, digoxin, ACEi/ARB, and beta blockers (each p&lt;0.0001), but also lower likelihood of filled prescriptions for pulmonary vasodilators, conventional diuretics (both p&lt;0.0001), and mineralocorticoid receptor antagonists (p=0.02).</p>

<p><strong>CONCLUSION: </strong>Pharmaceuticals typically used to treat heart failure and pulmonary hypertension are the most commonly prescribed medications following Fontan palliation. While the likelihood of treatment with a particular class of medication is associated with the age of the patient, determining the optimal regimen for individual patients and the population at large is an important knowledge gap for future research.</p>

<p>Background Protein-losing enteropathy (PLE) is a significant cause of morbidity and mortality in congenital heart disease patients with single ventricle physiology. Intrahepatic dynamic contrast-enhanced magnetic resonance lymphangiography (IH-DCMRL) is a novel diagnostic technique that may be useful in characterizing pathologic abdominal lymphatic flow in the congenital heart disease population and in diagnosing PLE. The objective of this study was to characterize differences in IH-DCMRL findings in patients with single ventricle congenital heart disease with and without PLE. Methods and Results This was a single-center retrospective study of IH-DCMRL findings and clinical data in 41 consecutive patients, 20 with PLE and 21 without PLE, with single ventricle physiology referred for lymphatic evaluation. There were 3 distinct duodenal imaging patterns by IH-DCMRL: (1) enhancement of the duodenal wall with leakage into the lumen, (2) enhancement of the duodenal wall without leakage into the lumen, and (3) no duodenal involvement. Patients with PLE were more likely to have duodenal involvement on IH-DCMRL than patients without PLE (&lt;0.001). Conclusions IH-DCMRL findings of lymphatic enhancement of the duodenal wall and leakage of lymph into the duodenal lumen are associated with PLE. IH-DCMRL is a useful new modality for characterizing pathologic abdominal lymphatic flow in PLE and might be useful as a risk-assessment tool for PLE in at-risk patients.</p>