sildenafil-citrate and Hypoplastic-Left-Heart-Syndrome

Topics: Adolescent; Budesonide; Fontan Procedure; Glucocorticoids; Humans; Hypoplastic Left Heart Syndrome; Male; Piperazines; Postoperative Complications; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

To determine sildenafil exposure and hemodynamic effect in children after stage II single-ventricle surgery.. Prospective, dose escalation trial.. Single-center, pediatric catheterization laboratory.. Twelve children poststage II single-ventricle surgical palliation and undergoing elective cardiac catheterization: median age 1.9 years (range, 0.8, 4.0), weight 11 kg (8, 13), nine females, and 10 with a single right ventricle.. Catheterization and echocardiography performed before and immediately after single-dose IV sildenafil (0.125, 0.25, 0.35, or 0.45 mg/kg over 20 min).. Peak sildenafil and desmethyl sildenafil concentration, change in hemodynamic parameters measured by cardiac catheterization and echocardiography including indexed pulmonary vascular resistance, and myocardial performance.. Maximum sildenafil concentrations ranged from 92 to 775 ng/mL and were above the in vitro threshold needed for 77% phosphodiesterase type 5 (PDE-5) inhibition in 80% of subjects and 90% inhibition in 80% of subjects with doses ≥0.35 mg/kg. Sildenafil lowered pulmonary vascular resistance index in all 12 subjects (median pulmonary vascular resistance index 2.2 [range, 1.6, 7.9]; decreased to 1.7 [1.2, 5.4] WU × m; p < 0.01) with no dose-response effect. Sildenafil improved pulmonary blood flow (+8% [0, 20], p = 0.04) and saturations (+2% [0, 16], p = 0.04) in those with baseline pulmonary vascular resistance index ≥ 2 WU × m (n = 7). Change in saturations correlated inversely with change in pulmonary vascular resistance index (r = 0.74, p < 0.01). Sildenafil also lowered mean blood pressure (-12% [-20, +10]; p = 0.04). There was no change in cardiac index and no effect on myocardial performance. There were no adverse events.. Sildenafil demonstrated nonlinear exposure with high interindividual variability but was well tolerated and effectively lowered pulmonary vascular resistance index in all subjects. Sildenafil did not acutely improve myocardial performance or increase cardiac index.

Topics: Cardiac Catheterization; Chemotherapy, Adjuvant; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heart Ventricles; Hemodynamics; Humans; Hypoplastic Left Heart Syndrome; Infant; Injections, Intravenous; Linear Models; Male; Palliative Care; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Ultrasonography; Vascular Resistance

A 19-day-old boy diagnosed with hypoplastic left heart syndrome underwent stage I bilateral pulmonary artery banding and main pulmonary artery-to-descending aorta shunt. A restrictive atrial septal defect existing before stage I recurred after balloon atrioseptostomy. After stage II Norwood and bidirectional Glenn procedure at age nine months, the Nakata index decreased to 73 mm(2)/m(2) (pulmonary artery mean pressure: 15 mmHg) and multiple systemic venous collaterals developed. Thus, we instituted oral sildenafil medication, and undertook surgical chest subcutaneous venous ligation and coil embolizations. Three years later, the Nakata index had increased to 117 mm(2)/m(2) (pulmonary artery mean pressure: 13 mmHg) and a Fontan procedure was successfully performed.

Topics: Administration, Oral; Anastomosis, Surgical; Aorta, Thoracic; Blood Pressure; Cardiac Surgical Procedures; Catheterization; Collateral Circulation; Combined Modality Therapy; Embolization, Therapeutic; Fontan Procedure; Heart Septal Defects, Atrial; Humans; Hypoplastic Left Heart Syndrome; Infant, Newborn; Ligation; Male; Palliative Care; Piperazines; Pulmonary Artery; Pulmonary Circulation; Purines; Radiography; Reoperation; Sildenafil Citrate; Sulfones; Thorax; Treatment Outcome; Vascular Resistance; Vasodilator Agents; Veins

Topics: Antihypertensive Agents; Bronchitis; Central Venous Pressure; Child, Preschool; Epoprostenol; Fontan Procedure; Humans; Hypertension; Hypoplastic Left Heart Syndrome; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

A 9.5-year-old girl after Fontan procedure for hypoplastic left heart syndrome had recurrent protein-losing enteropathy (PLE) develop 2 months after partial catheter closure of the Fontan fenestration. Despite satisfactory hemodynamic measurements under general anesthesia, we postulated that she suffered from increased pulmonary vascular reactivity and commenced her on Sildenafil treatment. After 6 weeks of oral Sildenafil treatment, her serum albumin and the fecal alpha-1-antitrypsin levels normalized, and her exercise tolerance had increased. There was also an improvement of the mesenteric arterial flow patterns on Doppler studies. Sildenafil should be considered in the treatment of PLE after the Fontan procedure.

Topics: Child; Female; Fontan Procedure; Humans; Hypoplastic Left Heart Syndrome; Piperazines; Protein-Losing Enteropathies; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents