sildenafil-citrate and Heart-Septal-Defects--Ventricular

Pulmonary hypertension is a common association in children with nonrestrictive ventricular septal defect. It increases perioperative mortality and morbidity. Oral sildenafil is an effective pulmonary vasodilator. In this study, we assessed effects of perioperative oral sildenafil therapy on pulmonary artery pressure and early surgical outcomes.. This was a single centre, prospective randomized control study. Thirty children with nonrestrictive ventricular septal defects with pulmonary hypertension were divided into two groups. In the sildenafil group (n = 15, mean age 23.3 months), oral sildenafil was administered two weeks before surgery. In the control group (n = 15, mean age 36 months), preoperative sildenafil was not given. Sildenafil was continued postoperatively in both groups, provided the postoperative pulmonary artery pressure was over 50% of systemic pressure.. There was no perioperative mortality, pulmonary hypertensive crisis and there were no intolerable side effects related to sildenafil in either group. Mean pulmonary artery pressure showed a reduction in both groups. Sildenafil group showed statistically significant improvement in duration of cardiopulmonary bypass (100.27 ± 21.09 min vs. 125.40 ± 26.83 min, p = .008), mechanical ventilation requirement (22.79 ± 17.13 h vs. 30.53 ± 13.05 h; p = .04), epinephrine requirement (22% patients vs. 48% patients; p = .03) and hospital stay (6.13 ± 1.40 days vs. 7.53 ± 1.92 days; p = .05).. Oral Sildenafil therapy is an inexpensive and well-tolerated method for reducing pulmonary hypertension secondary to non-restrictive ventricular septal defect. It has noteworthy advantages regarding early surgical outcomes like reduced cardiopulmonary bypass time, improved mechanical ventilation time, lower inotrope requirement and shorter hospital stay if used preoperatively in select patient population.

Topics: Child; Child, Preschool; Heart Septal Defects, Ventricular; Humans; Infant; Prospective Studies; Pulmonary Artery; Sildenafil Citrate; Treatment Outcome

Young children with CHD and large systemic-to-pulmonary shunts eventually develop pulmonary hypertension. At present, phosphodiesterase type-5 inhibitors such as sildenafil have been used to control pulmonary pressure before and after cardiac surgery. Recently, tadalafil has been utilised in older children with similar efficacy, but it has been used to a lesser extent in young infants. From April, 2015 to June, 2016, 42 patients aged 3-24 months with a large septal defect and pulmonary arterial hypertension were randomly divided into two equal groups: one group received oral sildenafil (1-3 mg/kg/day every 8 hours), whereas the other group received oral tadalafil (1 mg/kg once a day) from 7-10 days before surgery to 3-4 weeks after surgery. During the first 48 hours after surgery, pulmonary artery-to-aortic pressure ratio and recorded systolic pulmonary artery pressures were not significantly different between the two groups (p>0.05); moreover, there were no differences in paediatric ICU length of stay, mechanical ventilation time, clinical findings of low cardiac output state, and echocardiographic data between the two groups (p>0.05). Most of the patients had no side effects, and only five patients had a minor with no significant difference in both groups (p=0.371). Tadalafil can be considered as an effective oral therapy for preoperative and postoperative pulmonary hypertension in young infants. It can be administered at a once-daily dose with an appropriate efficacy and safety profile as sildenafil, and therefore it can be considered as an alternative to sildenafil in young children.

Topics: Cardiac Surgical Procedures; Child, Preschool; Echocardiography; Female; Heart Defects, Congenital; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Infant; Iran; Length of Stay; Male; Phosphodiesterase 5 Inhibitors; Pulmonary Artery; Sildenafil Citrate; Tadalafil; Treatment Outcome

Pulmonary hypertension in paediatric patients with ventricular septal defect remains one of the most important determinants of perioperative morbidity and mortality. Sildenafil is an oral, well-tolerated pulmonary vasodilator with few drug interactions. We studied the effect of oral sildenafil, when given before and after surgical closure compared with starting it postoperatively, on the pulmonary artery pressure and patients' outcome.. We enrolled 101 infants with large ventricular septal defects who had moderate-to-severe pulmonary hypertension scheduled for surgical closure. They were randomly assigned to the sildenafil group (n = 51, mean age 10 months and mean weight 6.5 kg), in which oral sildenafil was started 2 weeks before surgery to be continued postoperatively, and to the control group (n = 50, mean age 11 months and mean weight 7.3 kg), in which sildenafil was started only postoperatively. It was started at 0.5 mg/kg and increased gradually to a maximum dose of 2 mg/kg in both groups.. Overall hospital mortality was 4.9%. Mean pulmonary artery pressure decreased significantly at all time points of recording in both groups (P < 0.0001). In the sildenafil group, it decreased preoperatively after sildenafil administration from 75.4 to 59.4 mmHg and postoperatively from 50.4 mmHg immediate post-cardiopulmonary bypass to reach 44.2 mmHg before discharge. In the control group, it decreased from 74.6 mmHg to 51 mmHg immediate post-cardiopulmonary bypass to reach 42.7 mmHg before discharge. No adverse effects have been recorded. Although there was no difference in the duration of mechanical ventilation and hospital stay between the two groups, intensive care unit stay was significantly shorter in the sildenafil group. Dobutamine doses were significantly higher in the sildenafil group; however, milrinone and epinephrine have been used more significantly in the control group.. The low cost, the oral availability and the good tolerability of sildenafil make it a suitable and simple alternative therapy for secondary pulmonary hypertension including persistent postoperative pulmonary hypertension associated with ventricular septal defect in resource limited places. However, starting sildenafil early before surgery does not add a great benefit in terms of improving postoperative pulmonary hypertension or patients' outcome.

Topics: Administration, Oral; Antihypertensive Agents; Arterial Pressure; Cardiac Surgical Procedures; Drug Administration Schedule; Egypt; Female; Heart Septal Defects, Ventricular; Hospital Mortality; Humans; Hypertension, Pulmonary; Infant; Length of Stay; Male; Perioperative Care; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Pulmonary Artery; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Vasodilator Agents

The difference in underlying pathophysiology in different congenital heart disease (CHD) may have an influence on clinical outcome. It remains unclear whether the effect of sildenafil on pulmonary arterial hypertension (PAH) varies in different types of CHD.. The potential effect of sildenafil on pulmonary arterial hypertension related to CHD may be associated with shunt location.. In this 12-week, prospective, open label, multicenter trial, 55 patients with CHD were divided into the 3 groups: atrial septal defects group (ASD, n = 15), ventricular septal defects group (VSD, n = 24), and patent ductus arteriosus group (PDA, n = 16). Exercise capacity, hemodynamic parameters, and arterial oxygen saturation were assessed at baseline and after sildenafil therapy (25 mg, 3 times daily).. Six-minute walk distance significantly increased from 377.2 ± 68.7 m to 436.0 ± 70.4 m in patients with ASD, from 371.2 ± 66.0 m to 413.7 ± 83.1 m in VSD, and from 384.3 ± 90.2 m to 440.9 ± 71.8 m in PDA (P<0.01, respectively). Moreover, sildenafil also improved the pulmonary vascular resistance and pulmonary blood flow index in the 3 groups, whereas no significant changes in systemic vascular resistance and systemic arterial pressure were observed. However, arterial oxygen saturation was significantly improved in the ASD group only. The incidence of adverse events was similar among the 3 groups.. Sildenafil therapy seems to be effective and safe for PAH secondary to ASD, VSD, and PDA, although some clinical and hemodynamic parameters were changed in a different manner among the 3 groups.

Topics: Adolescent; Adult; Antihypertensive Agents; Chi-Square Distribution; China; Ductus Arteriosus, Patent; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Heart Defects, Congenital; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Oxygen; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Vasodilator Agents; Young Adult

This study evaluates the efficacy and safety of sildenafil in patients with Eisenmenger's syndrome with special emphasis on haemodynamic parameters and its comparative efficacy in atrial septal defect versus ventricular septal defect patients.. Oral sildenafil was given to 22 patients with Eisenmenger's syndrome - eight with atrial septal defect and 14 with ventricular septal defect - after detailed baseline evaluation including a six-minute walk test, echocardiography, and cardiac catheterisation. Patients were followed up for a period of 6 months for functional class assessment and six-minute walk distance. Cardiac catheterisation was repeated in all patients.. A significant improvement in the World Health Organization functional class, six-minute walk distance, mean pulmonary arterial pressure, and pulmonary vascular resistance was noticed. Systemic arterial and mixed venous oxygen saturations were also significantly improved along with improvement in pulmonary blood flow. None showed any significant side effects or worsening of systemic arterial saturation. At baseline, mean pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary/systemic vascular resistance ratios were significantly higher in ventricular septal defect patients than in atrial septal defect patients. Atrial septal defect patients showed better response in clinical as well as haemodynamic parameters.. Sildenafil is an effective and safe agent for patients with Eisenmenger's syndrome. It improves their functional capacity as well as haemodynamic parameters. The beneficial effects are greater in patients with Eisenmenger's syndrome secondary to atrial septal defect than ventricular septal defect.

Topics: Administration, Oral; Adolescent; Adult; Cardiac Catheterization; Eisenmenger Complex; Female; Follow-Up Studies; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Hemodynamics; Humans; Male; Middle Aged; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents; Young Adult

To investigate the acute effects of intravenous sildenafil on haemodynamics and oxygenation, and its interaction with inhaled nitric oxide (iNO) in infants at risk of pulmonary hypertension early after cardiac surgery.. Prospective, randomised trial.. Paediatric intensive care unit of a children's hospital.. Sixteen ventilated infants early after closure of ventricular or atrioventricular septal defects, were randomly assigned to one of two groups. The study was completed in 15 infants.. Studies were commenced within 7 h of separation from bypass. Seven infants received iNO (20 ppm) first, with the addition of intravenous sildenafil (0.35 mg/kg over 20 min) after 20 min. Eight infants received sildenafil first, iNO was added after 20 min. Vascular pressures, cardiac output and a blood gas were recorded at 0, 20 and 40 min.. In infants receiving iNO first, iNO lowered the pulmonary vascular resistance index (PVRI) from 3.45 to 2.95 units (p=0.01); sildenafil further reduced PVRI to 2.45 units p<0.05). In those receiving sildenafil first, PVRI was reduced from 2.84 to 2.35 units (p<0.05) with sildenafil, and fell to 2.15 units (p=0.01) with the addition of iNO. In both groups, sildenafil reduced the systemic blood pressure and systemic vascular resistance (p<0.01) and worsened arterial oxygenation and the alveolar-arterial gradient (p<0.05).. Intravenous sildenafil augmented the pulmonary vasodilator effects of iNO in infants early after cardiac surgery. However, sildenafil produced systemic hypotension and impaired oxygenation, which was not improved by iNO.

Topics: Administration, Inhalation; Blood Pressure; Bronchodilator Agents; Cardiac Output; Drug Synergism; Drug Therapy, Combination; Female; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Infusions, Intravenous; Male; Nitric Oxide; Piperazines; Postoperative Complications; Prospective Studies; Pulmonary Circulation; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Treatment Outcome; Vascular Resistance; Vasodilator Agents

Delayed diagnosis in children with a ventricular septal defect (VSD) is common in low- and middle-income countries. Consequently, these children present with elevated pulmonary vascular resistance (PVR) and pulmonary arterial hypertension (PAH). The study investigators introduced the double-flap valve VSD patch closure technique (DFV) in 1996 to reduce early postoperative risk. Long-term results are presented in this report.. This was a retrospective single-institution study of patients who underwent DFV between May 1996 and July 2015. Beginning in 2005, all candidates for DFV received sildenafil preoperatively and postoperatively. Preoperative catheterization data and operative, postoperative, hospital, and follow-up data were analyzed.. A total of 40 patients underwent the DFV procedure. Patients' demographics were comparable between the sildenafil and nonsildenafil groups. One of 39 patients (2.6%) was lost to follow-up. Early mortality was 2.5% (1 of 40), and late mortality was 2.6% (1 of 38). Sildenafil improved preoperative oxygen saturation, improved preoperative hemodynamics, and shortened postoperative ventilation time. In both groups, abnormal hemodynamic values improved with a 100% oxygen challenge. The median age at late follow-up was 26.3 years (interquartile range [25%, 75%], 20.9, 29.9 years), and the median time since operation was 19.2 years (interquartile range, 11.4, 22.7 years). Current discharge survival was 97.3%. A total of 18% of patients had severe PAH in late follow-up. Multivariate analysis revealed only a baseline PVR-to-systemic vascular resistance ratio of 0.8 or greater as a significant predictor of late severe PAH.. Long-term follow-up demonstrated that 60% of the patients will achieve normal or nearly normal pulmonary artery pressures. Furthermore, the study demonstrated that sildenafil improves preoperative hemodynamics and postoperative management. Children with VSD, elevated PVR, and PAH should not be denied operation.

Topics: Adolescent; Child; Familial Primary Pulmonary Hypertension; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Oxygen; Pulmonary Arterial Hypertension; Retrospective Studies; Sildenafil Citrate; Treatment Outcome; Vascular Resistance

Topics: Heart Septal Defects, Ventricular; Humans; Pulmonary Artery; Sildenafil Citrate; Vascular Resistance

Topics: Heart Septal Defects, Ventricular; Humans; Pulmonary Artery; Sildenafil Citrate; Vascular Resistance

A 38-year-old male was diagnosed with unrepaired ventricular septal defect associated with severe pulmonary arterial hypertension, cyanosis, and significant exercise intolerance. His echocardiogram showed right ventricular dysfunction and moderate pericardial effusion with no signs of cardiac tamponade. He was treated with an intensive course of inhaled iloprost and sildenafil. He showed a dramatic clinical response; his saturation went up from 60% on admission to 90% on minimal oxygen with significant improvement in his symptoms and signs of heart failure and total resolution of pericardial effusion. On follow up 3 and 6 weeks later, he was stable and could walk 360 meters in a 6 minutes walk test with disappearance of pericardial effusion. With unavailability of intravenous prostacyclin, we have shown in this case that intensive administration of inhaled iloprost could be used intensively as a rescue therapy in severe cases of pulmonary arterial hypertension with excellent results. 

Topics: Administration, Inhalation; Adult; Exercise Test; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Iloprost; Male; Pericardial Effusion; Pericarditis; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Treatment Outcome; Vasodilator Agents

Topics: Antihypertensive Agents; Cardiac Surgical Procedures; Female; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Early closure of a large ventricular septal defect before the onset of elevated pulmonary vascular resistance is important. Pulmonary hypertensive events might cause significant morbidity or mortality, even when closure is performed after infancy. Therefore, treatment of pulmonary hypertension after surgery may be the most important issue affecting the prognosis. We describe successful treatment of pulmonary hypertension in a 25-year-old woman after closure of large ventricular septal defect, with inhaled nitric oxide, sildenafil, and bosentan.

Topics: Administration, Inhalation; Adult; Antihypertensive Agents; Bosentan; Cardiac Surgical Procedures; Drug Therapy, Combination; Female; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Nitric Oxide; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Vasodilator Agents

Topics: Adult; Antihypertensive Agents; Bosentan; Combined Modality Therapy; Drug Therapy, Combination; Eisenmenger Complex; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Iron, Dietary; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Vasodilator Agents

A 3-month-old boy with coarctation of the aorta (CoA), ventricular septal defect (VSD), atrial septal defect, and severe pulmonary hypertension (PH) underwent one-stage repair consisting of patch closure of VSD and coarctation repair. Inhalation of nitric oxide (iNO) was commenced to treat residual severe PH on the day of the operation. Oral sildenafil citrate was commenced on the day 1 and iNO was gradually weaned off on the day 3. There was no "rebound", severe increase in pulmonary artery pressure, which commonly occurs after discontinuation of iNO. Then the patient was extubated without any difficulties or recurrent PH. The oral sildenafil citrate therapy was ceased on the day 8. Prophylactic use of oral sildenafil citrate for PH might be an useful alternative to shorten the duration of iNO therapy and intensive care unit (ICU) stay in the selected patients after congenital open heart surgery.

Topics: Administration, Inhalation; Administration, Oral; Aortic Coarctation; Bronchodilator Agents; Cardiac Surgical Procedures; Child, Preschool; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Male; Nitric Oxide; Piperazines; Postoperative Period; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Administration, Inhalation; Blood Pressure; Bronchodilator Agents; Cardiomegaly; Child; Drug Administration Schedule; Electrocardiography; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Intubation, Intratracheal; Male; Nitric Oxide; Piperazines; Postoperative Care; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Time Factors; Vasodilator Agents