Late morbidity during childhood and adolescence in previously premature neonates after patent ductus arteriosus closure.

The health status of previously premature neonates after closure of a patent ductus arteriosus (PDA) was analyzed in childhood and adolescence. Physician questionnaires were used to study 180 hospital survivors among 210 consecutive premature neonates who underwent PDA closure between 1985 and 2005. Complete follow-up data were obtained for 129 patients (72%). During a median follow-up period of 7 years (range, 2-22 years), three late deaths (2.3%) had occurred. Only 45% of the patients were considered healthy. Morbidity included developmental delay (41.1%), pulmonary illness (12.4%), neurologic impairment (14.7%), hearing impairment (3.9%), gastrointestinal disease (3.1%), and thoracic deformity (1.2%). None of the adverse variables during the neonatal period (intraventricular hemorrhage, bradycardia apnea syndrome, bronchopulmonary dysplasia, pulmonary bleeding, hyaline membrane disease, artificial respiration time [continuous positive airway pressure + intubation], or necrotizing enterocolitis) statistically predicted respective system morbidity at the follow-up evaluation. Hyaline membrane disease (odds ratio, 2.5; p = 0.026) and longer hospitalization time (odds ratio, 1.2 days per 10 hospitalization days; p = 0.032) in the newborn period were significant predictors of an unhealthy outcome at the last follow-up evaluation. Survival until childhood after closure of a hemodynamically significant PDA in premature neonates is satisfactory. However, physical and neurodevelopmental co-morbidity persist for half of the patients, perhaps as a sequela of prematurity unrelated to ductus closure.

Cardio-pulmonary interaction in premature newborn with nasal continuous positive airways pressure (n-CPAP) respiratory assistance evaluated with echocardiography

Introduction: Nasal continuous positive airways pressure (n-CPAP) is an effective treatment in premature infants with respiratory distress. The cardio-pulmonary interactions secondary to n-CPAP are well studied in adults, but less well described in premature infants. We postulated that there could be important interactions with regard to the patent ductus arteriosus (PDA). Methods: Prospective study, approved by the local ethic committee. Premature infants less than 32 weeks gestation, _7 days-old, needing n-CPAP for respiratory distress, but without the need of additional oxygen were included in the study. Every patient had a first echocardiography with n-CPAP and then n-CPAP was retrieved. 3 hours later the echocardiography was repeated by the same investigator and then the patient replaced on n-CPAP. Results: 14 premature newborn were included, mean gestational age of 28 _ 2 weeks, mean weight 1.1 _ 0.3 Kg and height 39 _ 3 cm. Echocardiographic measurements are depicted in Table 1. Significant finding were observed between measurement on n- CPAP or without n-CPAP: on end diastolic left ventricular diameter (12.8 _ 1.6 mm vs. 13.5 _ 2 mm), on end systolic left ventricular diameter (8.4 _ 1.3 mm vs. 9.1 _ 1.5 mm), left atrium diameter (8.9 _ 2.2 mm vs. 10.4 _ 2.5 mm), maximal velocity on tricuspid valve (46 _ 10 cm/s vs. 51 _ 9 cm/s), calculated Qp (3.7 _ 0.8 L/min/m2 vs. 4.3 _ 0.8 L/min/m2). Only three patients have demonstrated a PDA during the study. Conclusion: Positive end expiratory pressure (Peep) has hemodynamic effects which are: reduction of systemic and pulmonary venous return as shown by the changes on tricuspid valve inflow,on the calculated Qp and finally on the diameter of the left atrium and left ventricle.We found in premature infants the same hemodynamic effects than those described in adults but with lower Peep values. This could be due to the particular elasticity and weakness of the thoracic wall of premature infants. Interestingly the flow through a PDA seems also to be diminished with Peep, but the number of patients is insufficient to conclude. Further investigation will be needed to better understand these interactions. Table 1. Echocardiographic measurement (mean (SD)). With n-CPAP Without n-CPAP p value RV ED diameter (mm) 6.3 (1.7) 6.04 (1.1) NS LV ED diameter (mm) 12.8 (1.6) 13.5 (2.0) _0.05 LV ES diameter (mm) 8.4 (1.3) 9.1 (1.5) _0.05 SF (%) 34 (5) 33 (6) NS Ao valve diameter (mm) 7.4 (1.3) 7.4 (1.2) NS LA diameter (mm) 8.9 (2.2) 10.4 (2.5) _0.05 Vmax Ao (cm/s) 70 (16) 71 (18) NS Vmax PV (cm/s) 69 (15) 72 (16) NS Vmax TV (cm/s) 46 (10) 51 (9) _0.05 Vmax MV (cm/s) 53 (17) 54 (18) NS Qp (L/min/m2) 3.7 (0.8) 4.3 (0.8) _0.05 Qs (L/min/m2) 4.0 (0.8) 4.0 (0.7) NS Qp/Qs 0.92 (0.14) 1.09 (0.23) _0.05 RV: right ventricle, LV: left ventricle, ED: end diastolic, ES: end systolic, SF: shortening fraction,Ao: aortic valve, LA: left atrium,Vmax: maximum Doppler Velocity, Qp: pulmonary output, Qs: systemic output, NS: non significant.

Carotid-Subclavian Artery Index : Validation of an Echocardiographic Index to Detect Coarctation : P67

Introduction: Due to patency of the arterial duct and the parallel circulation during the fetal life, coarctation remains a difficult diagnosis prenatally and even shortly after birth. Fisrtly, our study aimed to assess accuracy of a new cardiographie index based on morphologie measurements of the distal aortic arch, the Carotid-Subclavian Artery Index (CSA Index), the ratio of the distal transverse aortic arch diameter to the distance between the left carotid artery and the left subclavian artery, in detecting coarctation in newborns, infants and children, independently of other cardiac lesions. Secondly, to assess the additive value of another morphologie index in predicting coarctation, the 1/0 ratio, the ratio of isthmus to descending aorta diameter. Methods: It is a retrospective cohort study in a tertiary care children's hospital. Offline echocardiographic measurements of great vessels and aortic arch dimensions were done in 69 patients with coarctation. We calculate their CSA index, and their 1/0 ratio. Values of CSA Index and 1/0 ratio from coarctation group were compared with those from a normal local control population. Results: 69 echocardiograms from patients with coarctation were analysed. Compared with controls, patients with coarctation had a significantly lower CSA index (0.88 ±0.49 vs 2.65 ±0.82, p <0.0001) and 1/0 ratio. The same significant difference was observed, independently of age and other associated defects, even complex ones. CSA Index confirmed its good sensitivity and specificity (99% and 96% respectively). This was not improved by adding the I/D ratio. Conclusions: An abnormal CSA index is highly suggestive of coarctation independently of age, of the presence of a patent ductus arteriosus or of other cardiac defects. The addition of another anatomie index, the I/D ratio, was not helpful in our study.

Remote control of pulmonary blood flow: a dream comes true.

The indication for pulmonary artery banding is currently limited by several factors. Previous attempts have failed to produce adjustable pulmonary artery banding with reliable external regulation. An implantable, telemetrically controlled, battery-free device (FloWatch) developed by EndoArt SA, a medical company established in Lausanne, Switzerland, for externally adjustable pulmonary artery banding was evaluated on minipigs and proved to be effective for up to 6 months. The first human implant was performed on a girl with complete atrioventricular septal defect with unbalanced ventricles, large patent ductus arteriosus and pulmonary hypertension. At one month of age she underwent closure of the patent ductus arteriosus and FloWatch implantation around the pulmonary artery through conventional left thoracotomy. The surgical procedure was rapid and uneventful. During the entire postoperative period bedside adjustments (narrowing or release of pulmonary artery banding with echocardiographic assessment) were repeatedly required to maintain an adequate pressure gradient. The early clinical results demonstrated the clinical benefits of unlimited external telemetric adjustments. The next step will be a multi-centre clinical trial to confirm the early results and adapt therapeutic strategies to this promising technology.

The renal hemodynamic effects of ibuprofen in the newborn rabbit.

In early childhood, nonsteroidal anti-inflammatory drugs are mainly used to either prevent or treat premature labor of the mother and patent ductus arteriosus of the newborn infant. The most frequently used prostaglandin-synthesis inhibitor is indomethacin. Fetuses exposed to indomethacin in utero have been born with renal developmental defects, and in both the unborn child and the term and premature newborn this drug may compromise renal glomerular function. The latter has in the past also been observed when i.v. indomethacin or i.v. acetylsalicylic acid (aspirin) were administered to newborn rabbits. The present experiments were designed to evaluate whether ibuprofen has less renal side effects than indomethacin, as claimed. Three groups of anesthetized, ventilated, normoxemic neonatal rabbits were infused with increasing doses of ibuprofen (0.02, 0.2, 2.0 mg/kg body weight) and the following renal parameters were measured: urine volume, urinary sodium excretion, GFR, and renal plasma flow. Renal blood flow, filtration fraction, and the renal vascular resistance were calculated according to standard formulae. Intravenous ibuprofen caused a dose-dependent, significant reduction in urine volume, GFR, and renal blood flow with a fall in filtration fraction in the animals receiving the highest dose of ibuprofen (2 mg/kg body weight). There was a very steep rise in renal vascular resistance. Urinary sodium excretion decreased. These experiments in neonatal rabbits clearly show that acute i.v. doses of ibuprofen also have significant renal hemodynamic and functional side effects, not less than seen previously with indomethacin.

Carotid-subclavian arteries Index (CSI), a new echocardiographic index to recognize coarctation of the aorta in neonates and infants

Introduction: Coarctation of the aorta is a common congenital heart malformation. Mode of diagnosis changed from clinically to almost exclusively by echocardiogram and MRI. We claim to find a new echocardiographic index, based on simple and reliable morphologic measurements, to facilitate the diagnosis of aortic coarctation in the newborn.We reproduce the same procedure for older child to validate this new index. Material and Methods: We reviewed echocardiographic studies of 47 neonates with diagnosis of coarctation who underwent cardiac surgery between January 1997 and February 2003 and compared them with a matched control group. We measured 12 different sites of the aorta, aortic arch and the great vessels on the echocardiographic bands. In a second time we reviewed 23 infants for the same measurements and compare them with a matched control group. Results: 47 neonates with coarctation were analysed, age 11.8 _ 10 days,weight 3.0 _ 0.6 kg, body surface 0.20 _ 0.02m2. The control group was of 16 newborns aged 15.8 _ 10 days,weight 3.2 _ 0.9 kg and body surface 0.20 _ 0.04m2. A significant difference was noted in many morphologic measurement between the both groups, the most significant being the distance between the left carotid artery and the left subclavian artery (coarctation vs control: 7.3 _ 3mm vs 2.4 _ 0.8mm, p _ 0.0001). We then defined a new index, the carotid-subclavian arteries index (CSI) as the diameter of the distal tranverse aortic arch divided to the distance left carotid artery to left subclavian artery being also significaly different (coarctation vs control: 0.76 _ 0.86 vs 2.95 _ 1.24, p _ 0.0001). With the cutoff value of this index of 1.5 the sensitivity for aortic coarctation was 98% and the specificity of 92%. In an older group of infant with coarctation (16 patients) we apply the same principle and find for a cut-off value of 1.5 a sensitivity of 95% and a specificity of 100%. Conclusions: The CSI allows to evaluate newborns and infants for aortic coarctation with simple morphologic measurement that are not depending of the left ventricular function, presence of a patent ductus arteriosus or not. Further aggressive evaluation of these patient with a CSI _ 1.5 is indicated.

Validation of two echocardiographic indexes to improve the diagnosis of complex coarctations.

OBJECTIVES: Coarctation of the aorta is one of the most common congenital heart defects. Its diagnosis may be difficult in the presence of a patent ductus arteriosus, of other complex defects or of a poor echocardiographic window. We sought to demonstrate that the carotid-subclavian artery index (CSA index) and the isthmus-descending aorta ratio (I/D ratio), two recently described echocardiographic indexes, are effective in detection of isolated and complex aortic coarctations in children younger and older than 3 months of age. The CSA index is the ratio of the distal aortic arch diameter to the distance between the left carotid artery and the left subclavian artery. It is highly suggestive of a coarctation when it is <1.5. The I/D ratio defined as the diameter of the isthmus to the diameter of the descending aorta, suggests an aortic coarctation when it is less than 0.64. METHODS: This is a retrospective cohort study in a tertiary care children's hospital. Review of all echocardiograms in children aged 0-18 years with a diagnosis of coarctation seen at the author's institution between 1996 and 2006. An age- and sex-matched control group without coarctation was constituted. Offline echocardiographic measurements of the aortic arch were performed in order to calculate the CSA index and I/D ratio. RESULTS: Sixty-eight patients were included in the coarctation group, 24 in the control group. Patients with coarctation had a significantly lower CSA index (0.84+/-0.39 vs 2.65+/-0.82, p<0.0001) and I/D ratio (0.58+/-0.18 vs 0.98+/-0.19, p<0.0001) than patients in the control group. Associated cardiac defects and age of the child did not significantly alter the CSA index or the I/D ratio. CONCLUSIONS: A CSA index less than 1.5 is highly suggestive of coarctation independent of age and of the presence of other cardiac defects. I/D ratio alone is less specific than CSA alone at any age and for any associated cardiac lesion. The association of both indexes improves sensitivity and permits diagnosis of coarctation in all patients based solely on a bedside echocardiographic measurement.

Can dopamine prevent the renal side effects of indomethacin? A prospective randomized clinical study.

BACKGROUND: Indomethacin therapy for closure of a patent ductus arteriosus in preterm neonates is responsible for transient renal insufficiency. Dopamine theoretically reduces the renal side effects of indomethacin therapy. PATIENTS: 33 neonates with a mean gestational age of 28.5 weeks who received indomethacin for treatment of a symptomatic PDA were included in a prospective randomized controlled clinical study. METHOD: 15 patients were treated with indomethacin alone (control group), 18 patients with indomethacin and dopamine (study group). Indomethacin was given in a dose of 0.2 mg/kg/dose intravenously, all patients received three doses with intervall of 12 hours. The dose of dopamine was in all patients 4 micrograms/kg per minute commencing 2 hours prior to the first dose of indomethacin and continuing for 12 hours after the third dose. RESULTS: Indomethacin induced a significant increase in serum creatinin (76.3 mumol/l vs 99.7 mumol/l for the control group, and 70.7 mumol/l vs 93.0 mumol/l for the study group), and weight (1259 g vs 1316 g for the control group, and 1187 g vs 1221 g for the study group). The increase systolic blood pressure (61 mmHg vs 65.7 mmHg) in the study group was significant (p < 0.05) but remained unchanged in the control group. The changes between the study group and the control group were not significant either in serum creatinin, fractional excretion of sodium, or weight gain. The failure rate of ductal closure was not different between the two groups. CONCLUSION: The additional use of dopamine does not reduce the renal side effects of indomethacin.

Advances in paediatric interventional cardiology since 2000.

Interventional paediatric and congenital cardiology is expanding at a rapid pace. Validated techniques (such as aortic or pulmonary valve dilatations and occlusion of persistent ductus arteriosus and atrial septal defects) are improving thanks to the use of smaller introducers and sheaths, low-profile balloons and novel devices. Moreover, catheter-based interventions have emerged as an attractive alternative to surgery in other fields: pulmonary valve replacement, balloon and stent implantation for native and recurrent coarctation, and percutaneous closure of ventricular septal defects. On the other hand, percutaneous interventions in the paediatric population may be limited by patient size or the anatomy of the defect. Hybrid approaches involving both cardiac interventionists and surgeons are being developed to overcome these limitations. Based on a better understanding of cardiac development, fetal cardiac interventions are being attempted in order to alter the history of severe obstructive lesions. Finally, some interventional procedures still carry a low success rate-for example, pulmonary vein stenosis, even with the use of conventional stents. Biodegradable stents and devices are being developed and may find an application in this setting as well as in others. The purpose of this review is to highlight the advances in paediatric interventional cardiology since the beginning of the third millennium.

Percutaneous closure of patent foramen ovale: head-to-head comparison of two different devices

Percutaneous closure of patent foramen ovale (PFO) has been proposed as the treatment of choice for young high-risk patients who suffered cryptogenic stroke and/or peripheral paradoxical embolism. We sought to compare prospectively two different devices used for percutaneous PFO closure.Prospective data were collected on 40 high risk patients (females: 38%, mean age : 44 +/- 11 years, interatrial septal aneurysm >10 mm: 68%) who underwent percutaneous PFO closure after cryptogenic stroke (n = 38) or peripheral paradoxical embolism (n = 2). Chronologically, 20 patients were first treated by a PFO-Star (Cardia, Burnsville, MI) device. Then, 20 other patients received a Starflex occluder (NMT, Boston, MA). The primary endpoint was complete PFO closure at 6 months as assessed by transthoracic contrast echocardiography. Secondary endpoints were major peri- or post procedural complications and clinical recurrence at 1 year follow-up.Baseline clinical and anatomical characteristics were comparable for both groups. Complete PFO closure was observed in 50% (PFO-Star) and 90% (Starflex) of patients (p=0.001) respectively. Major peri-procedural complications occurred in the PFO-star group only: right-sided device thrombus (1 patient) and aorto-right atrial fistula (1 patient). At 1 year follow-up, no clinical recurrence occurred.In conclusion, despite the absence of clinical recurrence in this high-risk population with presumed paradoxical embolism, complete PFO closure at 6 months follow-up was significantly related to the type of closure device used

Controlled contrast transcranial Doppler and arterial blood gas analysis to quantify shunt through patent foramen ovale.

BACKGROUND AND PURPOSE: A right-to-left shunt can be identified by contrast transcranial Doppler ultrasonography (c-TCD) at rest and/or after a Valsalva maneuver (VM) or by arterial blood gas (ABG) measurement. We assessed the influence of controlled strain pressures and durations during VM on the right-to-left passage of microbubbles, on which depends the shunt classification by c-TCD, and correlated it with the right-to-left shunt evaluation by ABG measurements in stroke patients with patent foramen ovale (PFO). METHODS: We evaluated 40 stroke patients with transesophageal echocardiography-documented PFO. The microbubbles were recorded with TCD at rest and after 4 different VM conditions with controlled duration and target strain pressures (duration in seconds and pressure in cm H2O, respectively): V5-20, V10-20, V5-40, and V10-40. The ABG analysis was performed after pure oxygen breathing in 34 patients, and the shunt was calculated as percentage of cardiac output. RESULTS: Among all VM conditions, V5-40 and V10-40 yielded the greatest median number of microbubbles (84 and 95, respectively; P&lt;0.01). A significantly larger number of microbubbles were detected in V5-40 than in V5-20 (P&lt;0.001) and in V10-40 than in V10-20 (P&lt;0.01). ABG was not sensitive enough to detect a shunt in 31 patients. CONCLUSIONS: The increase of VM expiratory pressure magnifies the number of microbubbles irrespective of the strain duration. Because the right-to-left shunt classification in PFO is based on the number of microbubbles, a controlled VM pressure is advised for a reproducible shunt assessment. The ABG measurement is not sensitive enough for shunt assessment in stroke patients with PFO.

Patent foramen ovale and obstructive sleep apnoea: from pathophysiology to diagnosis of a potentially dangerous association.

Patent foramen ovale and obstructive sleep apnoea are frequently encountered in the general population. Owing to their prevalence, they may coexist fortuitously; however, the prevalence of patent foramen ovale seems to be higher in patients with obstructive sleep apnoea. We have reviewed the epidemiological data, pathophysiology, and the diagnostic and therapeutic options for both patent foramen ovale and obstructive sleep apnoea. We focus on the interesting pathophysiological links that could explain a potential association between both pathologies and their implications, especially on the risk of stroke.