Beat Friedli

Inhaled Nitric Oxide Versus Aerosolized Iloprost in Secondary Pulmonary Hypertension in Children With Congenital Heart Disease Vasodilator Capacity and Cellular Mechanisms

Background —Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. Methods and Results —A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng · kg−1 · min−1 for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48±0.38 to 0.27±0.16 (P <0.001). Similarly, iloprost decreased the ratio from 0.49±0.38 to 0.26±0.11 (P <0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6±11.9 to 34.7±21.4 nmol/L during iNO (P <0.01), and plasma cAMP increased from 55.7±22.9 to 65.1±21.2 nmol/L during iloprost inhalation (P <0.05). Conclusions —In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

Transcatheter closure of atrial septal defect and patent foramen ovale with the ASDOS device (a multi-institutional European trial)∗

A clinical trial was conducted to assess the feasibility, safety, and efficacy of the atrial septal defect (ASD) occlusion system for transcatheter closure of secundum ASD and patent foramen ovale (PFO) after episodes of cerebral embolism. Occlusion was attempted in 200 patients aged 1 to 74 years (mean 32). The procedure failed in 26 patients (13%); the device was retrieved through a catheter in 20 and through surgery in 6 patients. Procedure-related complications necessitating surgical removal of the device included device embolization in 2, device entrapment within the Chiari network in 1, frame fracture in 1, and perforation of atrial wall in 2. All 6 patients experienced an uneventful postoperative course. An additional 11 patients (6%) underwent surgical removal of the device during follow-up. There were 163 patients (81%) with an implanted ASD occlusion system at follow-up of from 6 to 36 months (mean 17). Thrombus formation around the device was detected by transesophageal echocardiography in 9 patients 1 to 4 weeks after implantation. One of these patients (who had a coagulation factor XII deficiency) suffered a cerebral thromboembolism. Late atrial wall perforation (5, 6, and 8 months after implantation) occurred in 3 adult patients. Infectious endocarditis developed in 2 adult patients (1%). No late device embolization and no atrioventricular valve injury occurred. An asymptomatic device frame fracture was found in 14% and frame deformity in 4% of all patients during the follow-up period of >230 patient-years. Immediately after closure, a moderate/large residual shunt remained in 8% and a small shunt in 29% of patients. After 1 year, a moderate/large shunt was present in 2% and a small one in 26% of patients. During a total follow-up of 49 patient-years, only 1 of 46 patients with PFO had a transient neurologic event after the closure. The study indicates that patients with centrally situated secundum ASD and those with PFO after cerebral embolism can be treated with this system with a high success rate and an acceptable morbidity.

Continuous low dose inhaled nitric oxide for treatment of severe pulmonary hypertension after cardiac surgery in paediatric patients.

OBJECTIVE--To assess the effect of inhaled nitric oxide (NO) on severe postoperative pulmonary hypertension in children after surgical repair of a congenital heart defect. DESIGN--A pilot study of NO administration to 7 consecutive children who required adrenergic support and in whom postoperative mean pulmonary artery pressure was more than two thirds of mean systemic pressure and persisted despite alkalotic hyperventilation. SETTING--Routine care after cardiac surgery for congenital heart disease in a multidisciplinary paediatric intensive care unit. METHODS--Continuous inhalation of NO, initially at 15 ppm. Therefore, daily attempts at complete weaning or at reducing NO to the lowest effective dose. RESULTS--In 6 of the 7 children NO inhalation selectively decreased mean (SD) pulmonary artery pressure from 51 (12) to 31 (9) mm Hg (P < 0.05) while mean systemic arterial pressure was unchanged (68 (10) v 71 (7) mm Hg) (NS) and the arteriovenous difference in oxygen content decreased from 6.7 (0.9) to 4.8 (0.8) vol% (P < 0.05). Concomitantly PaO2 increased from 158 (98) to 231 (79) mm Hg) (P < 0.05). The seventh child showed no response to NO up to 80 ppm, could not be weaned from cardiopulmonary bypass, and died in the operating room. In responders, attempts at early weaning from NO inhalation always failed and NO at concentrations of less than 10 ppm was continuously administered for a median of 9.5 days (range 4 to 16 days) until complete weaning was possible from a mean dose of 3.9 (2.9) ppm. Methaemoglobinaemia remained below 2% and nitrogen dioxide concentrations usually ranged from 0.1 to 0.2 ppm. One child later died and five were discharged. A few months after surgery Doppler echocardiography (and catheterisation in one) showed evidence of regression of pulmonary hypertension in all 5. CONCLUSIONS--Inhalation of NO reduced pulmonary artery pressure in children with severe pulmonary hypertension after cardiac surgery and this effect was maintained over several days at concentrations carrying little risk of toxicity.

Inhaled Nitric Oxide to Test the Vasodilator Capacity of the Pulmonary Vascular Bed in Children With Long-Standing Pulmonary Hypertension and Congenital Heart Disease

Nitric oxide-induced vasodilator capacity greatly varies among children with pulmonary hypertension and elevated vascular resistance. The decline of this selective response seems to parallel the progression of established vascular disease and thus may be helpful for the selection of patients for operation.

Ventricular septal defect with increased pulmonary vascular resistance: Late results of surgical closure

Abstract The fate of 57 children who underwent surgical closure of ventricular septal defect in the presence of increased pulmonary vascular resistance was analyzed. Eighteen (32 percent) died at or immediately after operation. Seven late deaths, due to the Eisenmenger syndrome, occurred 1 to 7 years after operation. Follow-up studies, including cardiac catheterization, were performed in 25 survivors, 1 to 11 years (mean 5 years) after operation. In patients operated on after age 2 years, the degree of preoperative elevation of pulmonary vascular resistance largely determined the prognosis: The condition of patients with mild elevation (pulmonary vascular resistance less than one third the systemic level) returned to normal after operation, with one exception. Patients with more severe elevation (pulmonary vascular resistance more than one third the systemic level) most often showed progressive pulmonary vascular disease; the condition of a few remained unchanged and that of only one returned to normal after operation. Operative mortality rate was high in children with elevated pulmonary vascular resistance during the second year of life who were operated on before age 2 years, but pulmonary vascular resistance returned to normal in the three survivors. When pulmonary vascular resistance was increased in the first year of life, it generally decreased spontaneously (independently of operation); the early increase in these cases is believed to represent delayed maturation of the pulmonary vascular bed rather than pulmonary vascular disease. The overall results of surgery in ventricular septal defect associated with a high level of pulmonary vascular resistance are unfavorable and call for interruption of the natural history before significant pulmonary vascular obstructive changes have taken place; this can be achieved by surgical closure before age 2 years or pulmonary artery banding in infancy.

Morphologic and functional evaluation of congenital heart disease by magnetic resonance imaging

Magnetic resonance imaging (MRI) has evolved sufficiently to be recognized as a useful complementary noninvasive method to echocardiography in the evaluation of congenital heart disease (CHD). In some cases, MRI is superior to other imaging modalities, particularly in the evaluation of thoracic aortic anomalies and in defining the anatomy of central pulmonary arteries; it is also the procedure of choice in the postoperative follow‐up of patients with CHD. Recent technological advances permit not only morphological evaluation (provided by spin‐echo and MR angiographic techniques) but functional and flow information (provided by fast cine‐GE and velocity‐encoded sequences), causing it to be recognized by pediatric cardiologists and cardiac surgeons as an unavoidable technique for pre‐ and postoperative evaluation of some CHD. This review describes the various techniques used in the evaluation of CHD with emphasis on recent developments as well as recognized clinical applications. J. Magn. Reson. Imaging 1999;10:639–655.

Balloon aortic valvoplasty in paediatric patients: progressive aortic regurgitation is common

Objective: To evaluate immediate and midterm results after balloon valvoplasty in a paediatric population with congenital aortic stenosis, giving special consideration to aortic regurgitation. Design: Retrospective study. Setting: Two tertiary referral centres for paediatric cardiology. Patients: 70 consecutive patients, with an age range of 0–16.4 years. Group A infants < 3 months old (n  =  21). Group B children > 3 months old (n  =  49). Median follow up time was 19.8 months, range 0–158 months. Intervention: All patients underwent balloon aortic valvoplasty. The balloon to annulus ratio was selected at a mean of 0.90 (range 0.67–1.0). Main outcome measures: Doppler gradients and degree of aortic regurgitation. Results: The pressure gradient dropped significantly with the intervention and increased mildly at follow up. Freedom from relevant aortic regurgitation (that is, moderate and severe) was initially lower in group A (75% v 90% after one month) but after two years the difference between the two groups was not significant (50% v 61%). Freedom from reintervention was significantly lower in group A (with 35% v 80%) after three years. Conclusion: Aortic balloon valvoplasty is safe and effective but has a high rate of early reintervention in infants with critical aortic stenosis. The major long term problem is progressive aortic regurgitation, which does not seem to be prevented by the use of small balloons.

Coarctation of the aorta: pre and postoperative evaluation with MRI and MR angiography; correlation with echocardiography and surgery

AimsTo compare MRI and MRA with Doppler-echocardiography (DE) in native and postoperative aortic coarctation, define the best MR protocol for its evaluation, compare MR with surgical findings in native coarctation.Materials and methods136 MR studies were performed in 121 patients divided in two groups: Group I, 55 preoperative; group II, 81 postoperative. In group I, all had DE and surgery was performed in 35 cases. In group II, DE was available for comparison in 71 cases. MR study comprised: spin-echo, cine, velocity-encoded cine (VEC) sequences and 3D contrast-enhanced MRA.ResultsIn group I, diagnosis of coarctation was made by DE in 33 cases and suspicion of coarctation and/or aortic arch hypoplasia in 18 cases. Aortic arch was not well demonstrated in 3 cases and DE missed one case. There was a close correlation between VEC MRI and Doppler gradient estimates across the coarctation, between MRI aortic arch diameters and surgery but a poor correlation in isthmic measurements. In group II, DE detected a normal isthmic region in 31 out of 35 cases. Postoperative anomalies (recoarctation, aortic arch hypoplasia, kinking, pseudoaneurysm) were not demonstrated with DE in 50% of cases.ConclusionsMRI is superior to DE for pre and post-treatment evaluation of aortic coarctation. An optimal MR protocol is proposed. Internal measurement of the narrowing does not correspond to the external aspect of the surgical narrowing.

Stenting of superior vena cava and inferior vena cava for symptomatic narrowing after repeated atrial surgery for D-transposition of the great vessels.

Double venous stenting of the superior vena cava and inferior vena cava was successfully performed after failed balloon angioplasty in a young woman who had venoatrial narrowing and kinking after repeated Mustard procedure for D-transposition of great vessels. Self-expanding metallic stents were used. Angiography showed that the first stent was fully patient after six months when a second stent was implanted. This operation was followed by sustained clinical improvement. The present report shows the feasibility and success of stenting of the great veins when postoperative narrowing or kinking is unresponsive to balloon angioplasty alone.

Pediatric cardiologyVentricular septal defect with increased pulmonary vascular resistance: Late results of surgical closure☆

Abstract The fate of 57 children who underwent surgical closure of ventricular septal defect in the presence of increased pulmonary vascular resistance was analyzed. Eighteen (32 percent) died at or immediately after operation. Seven late deaths, due to the Eisenmenger syndrome, occurred 1 to 7 years after operation. Follow-up studies, including cardiac catheterization, were performed in 25 survivors, 1 to 11 years (mean 5 years) after operation. In patients operated on after age 2 years, the degree of preoperative elevation of pulmonary vascular resistance largely determined the prognosis: The condition of patients with mild elevation (pulmonary vascular resistance less than one third the systemic level) returned to normal after operation, with one exception. Patients with more severe elevation (pulmonary vascular resistance more than one third the systemic level) most often showed progressive pulmonary vascular disease; the condition of a few remained unchanged and that of only one returned to normal after operation. Operative mortality rate was high in children with elevated pulmonary vascular resistance during the second year of life who were operated on before age 2 years, but pulmonary vascular resistance returned to normal in the three survivors. When pulmonary vascular resistance was increased in the first year of life, it generally decreased spontaneously (independently of operation); the early increase in these cases is believed to represent delayed maturation of the pulmonary vascular bed rather than pulmonary vascular disease. The overall results of surgery in ventricular septal defect associated with a high level of pulmonary vascular resistance are unfavorable and call for interruption of the natural history before significant pulmonary vascular obstructive changes have taken place; this can be achieved by surgical closure before age 2 years or pulmonary artery banding in infancy.