Patent ductus arteriosus in adults – indications and possibilities for closure

Patent ductus arteriosus (PDA) is a rare diagnosis in adults, since symptoms and signs usually occur in infancy and most cases are treated shortly after diagnosis. We present two patients who were first diagnosed with PDA during adulthood. The first case represents a more severe form of PDA, where the need for closure of the PDA is obvious. In the second case the sequelae of the PDA are less clear. In both patients, closure of the PDA (surgically in one case, percutaneously in the other) was successful.     

Are Cytochrome P450 CYP2C8 and CYP2C9 Polymorphisms Associated with Ibuprofen Response in Very Preterm Infants?

Background

Patent ductus arteriosus (PDA) in extremely preterm infants remains a challenging condition with conflicting treatment strategies. Ibuprofen is currently used to treat PDA with ductal closure failure rate up to 40%. We test the hypothesis that cytochrome P450 CYP2C8/2C9 polymorphisms may predict ibuprofen response.

Methodology/Principal Findings

We studied extremely preterm neonates with haemodynamically significant PDA and treated with ibuprofen. One or two variant CYP2C8 and/or 2C9 alleles were found in 17% of the population, most of them were from Caucasian ethnicity (67–74%). Response to ibuprofen and clinical course of infants carrying variants CYP2C8 and CYP2C9 were similar. Comparing infants with wild type or variant CYP2C8 and CYP2C9 genotypes, response rate to ibuprofen was significantly higher in wild type than in mutated carriers in univariate analysis (73% versus 52%, p = 0.04). Comparing responders (ductus closure; n = 75) and non-responders (surgical ligation; n = 36), the only two factors significantly associated with the response to ibuprofen using multivariate analysis were higher gestational age and non Caucasian ethnicity but not CYP2C polymorphism.

Conclusions

CYP2C polymorphism was not associated with PDA response to ibuprofen and this factor appears not appropriate to optimize the ductal closure rate by modulating ibuprofen dosing strategy. This study points out the role for ethnicity in the interindividual variability of response to ibuprofen in extremely preterm infants.     

Comparison of Oral Paracetamol versus Ibuprofen in Premature Infants with Patent Ductus Arteriosus: A Randomized Controlled Trial

Trial Design

Oral ibuprofen has demonstrated good effects on symptomatic patent ductus arteriosus (PDA) but with many contraindications and potential side-effects. In the past two years, oral paracetamol administration to several preterm infants with PDA has been reported. Here, a randomized, non-blinded, parallel-controlled and non-inferiority trial was designed to evaluate the efficacy and safety profiles of oral paracetamol to those of standard ibuprofen for PDA closure in premature infants.

Methods

One hundred and sixty infants (gestational age ≤34 weeks) with echocardiographically confirmed PDA were randomly assigned to receive either oral paracetamol (n = 80) or ibuprofen (n = 80). After the initial treatment course in both groups, the need for a second course was determined by echocardiographic evaluation. The main outcome was rate of ductal closure, and secondary outcomes were adverse effects and complications.

Result

The ductus was closed in 65 (81.2%) infants of the paracetamol group compared with 63 (78.8%) of the ibuprofen group. The 95% confidence interval of the difference between these groups was [−0.080,0.128], demonstrating that the effectiveness of paracetamol treatment was not inferior to that of ibuprofen. In fact, the incidence of hyperbilirubinemia or gastrointestinal bleeding in the paracetamol group was significantly lower than that of the ibuprofen group. No significant differences in other clinical side effects or complications were noted.

Conclusion

This comparison of drug efficacy and safety profiles in premature infants with PDA revealed that oral paracetamol was comparable to ibuprofen in terms of the rate of ductal closure and even showed a decreased risk of hyperbilirubinemia or gastrointestinal bleeding. Therefore, paracetamol may be accepted as a first-line drug treatment for PDA in preterm infants.

Trial Registration

ChiCTR.org ChiCTR-TRC-12002177     

Altered plasma proteins released from platelets and endothelial cells are associated with human patent ductus arteriosus

Patent ductus arteriosus is the third most common congenital heart disease and resulted from the persistence of ductal patency after birth. Ductus arteriosus closure involves functional and structural remodeling, controlled by many factors. The changes in plasma protein levels associated with PDA closure are not known. Here we for the first time demonstrate six key differential plasma proteins in human patent ductus arteriosus patients using proteomic technology and present a model to illustrate the constriction and closure of ductus arteriosus. Differentially expressed proteins were analyzed by using isobaric tags for relative and absolute quantification and validated by enzyme-linked immunosorbent assay in new samples. The proteomic data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD008568. We found 74 upregulated and 98 downregulated proteins in the plasma of patients with PDA. Five decreased proteins (platelet factor 4, fibrinogen, von Willebrand factor, collagen, and mannose binding lectin-associated serine protease-2) and one increased protein (fibronectin) may increase the risk of patent ductus arteriosus. Those proteins are closely related to platelet activation and coagulation cascades, complement mannan-binding-lectin, and other systemic signaling pathways. Our findings for the first time indicate that the differential proteins involved in different pathways may play key roles in the nonclosure of the ductus arteriosus in humans and may be developed as biomarkers for diagnosis. All those findings may be served as the basis of understanding the etiology and pathogenesis of patent ductus arteriosus.     

Percutaneous closure of an adult patent ductus arteriosus

A 23-year-old asymptomatic male was referred to our outpatient clinic because of an incidentally discovered grade III continuous machinery murmur at the third intercostal space on the left sternal edge. The echocardiography showed the presence of a patent ductus arteriosus (PDA).     

A comparison of postoperative outcomes with PDA ligation in the OR versus the NICU: a retrospective cohort study on the risks of transport

Background

Although patent ductus arteriosus (PDA) ligations in the Neonatal Intensive Care Unit (NICU) have been an accepted practice, many are still performed in the Operating Room (OR). Whether avoiding transport leads to improved perioperative outcomes is unclear. Here we aimed to determine whether PDA ligations in the NICU corresponded to higher risk of surgical site infection or mortality and if transport was associated with worsened perioperative outcomes.

Methods

We performed a retrospective cohort study of NICU patients, ≤37?weeks post-menstrual age, undergoing surgical PDA ligation in the NICU or OR. We excluded any infants undergoing device PDA closure. We measured the incidence of perioperative hypothermia, cardiac arrest, decreases in SpO2, hemodynamic instability and postoperative surgical site infection, sepsis and mortality.

Results

Data was collected on 189 infants (100 OR, 89 NICU). After controlling for number of preoperative comorbidities, weight at time of procedure, procedure location and hospital in the mixed-effect model, no significant difference in mortality or sepsis was found (odds ratio 0.31, 95%CI 0.07, 1.30; p?=?0.107, and odds ratio 0.40; 95%CI 0.14, 1.09; p?=?0.072, respectively). There was an increased incidence of hemodynamic instability on transport postoperatively in the OR group (12.4% vs 2%, odds ratio 6.93; 95% CI 1.48, 35.52; p?=?0.014).

Conclusion

PDA ligations in the NICU were not associated with higher incidences of surgical site infection or mortality. There was an increased incidence of hemodynamic instability in the OR group on transport back to the NICU. Larger multicenter studies following long-term outcomes are needed to evaluate the safety of performing all PDA ligations in the NICU.

Keywords

Patent ductus arteriosus, Newborn infant, Neonatal intensive care unit, Surgical wound infection, Postoperative period, Hemodynamics

     

Attraction of the predator,Harmonia axyridis (Coleoptera: Coccinellidae), to its prey,Myzus persicae (Hemiptera: Aphididae), feeding on Chinese cabbage

The predatory multicolored Asian lady beetle, Harmonia axyridis, was attracted to volatiles released from Chinese cabbage infested by the green peach aphid, Myzus persicae, in T-tube olfactometer choice tests. However, lady beetle adults and larvae did not respond to clean air, Chinese cabbage alone or green peach aphid alone. Of different prey densities, H. axyridis adults were most attracted to Chinese cabbage infested by 60 M. persicae adults after 24 h. However, H. axyridis larvae were not attracted to Chinese cabbage infested by M. persicae. Mechanically damaged Chinese cabbage attracted neither lady beetle adults nor larvae. Predatory adults were attracted to 60 M. persicae adults after 24 and 48 h, and to 90 M. persicae adults after 12 h, suggesting that the predatory response depends on the prey density. Lady adult beetles did not prefer the volatiles induced by Diamondback moth, Plutella xylostella, indicating that specific host insect specificity attracts respective natural enemies. It can be explained that the volatile compounds emitted from the host plant as a result of herbivore attack preferred by the specific insect species.     

Intraguild predation of the aphid parasitoid Aphelinus certus by Coccinella septempunctata and Harmonia axyridis

Coincidental intraguild predation is expected to be less disruptive to biological control than omnivorous intraguild predation, and strong intraguild predation is not expected to occur in natural systems. Coincidental intraguild predation in a foodweb involving introduced pest and natural enemy species was examined to determine whether intraguild predation would be disruptive of biological control services in soybean agroecosystems. Introduced natural enemies are important regulators of soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), populations in North America. Seven-spotted lady beetles, Coccinella septempunctata L., and multicolored Asian lady beetles, Harmonia axyridis Pallas (Coleoptera: Coccinellidae), are key predators of soybean aphid in North America while the chalcidoid wasp, Aphelinus certus Yasnosh (Hymenoptera: Aphelinidae), is the most common parasitoid of soybean aphid in Ontario, Canada. Predation of parasitized soybean aphids at two stages (newly parasitized aphids and mummified aphids) by adults and third instar larvae of both C. septempunctata and H. axyridis was examined in laboratory experiments. In choice experiments, all stages of lady beetles preferred non-parasitized aphids over mummified aphids. In cage experiments, third instar larvae and male and female adults of both lady beetles did not discriminate between newly parasitized and non-parasitized aphids. The influence of coincidental intraguild predation on the efficacy of parasitoids as biological control agents, and implications for soybean aphid management decisions based on natural enemies, are discussed.     

Cardiac remodelling: concentric versus eccentric hypertrophy in strength and endurance athletes

Cardiac remodelling is commonly defined as a physiological or pathological state that may occur after conditions such as myocardial infarction, pressure overload, idiopathic dilated cardiomyopathy or volume overload. When training excessively, the heart develops several myocardial adaptations causing a physiological state of cardiac remodelling. These morphological changes depend on the kind of training and are clinically characterised by modifications in cardiac size and shape due to increased load. Several studies have investigated morphological differences in the athlete’s heart between athletes performing strength training and athletes performing endurance training. Endurance training is associated with an increased cardiac output and volume load on the left and right ventricles, causing the endurance-trained heart to generate a mild to moderate dilatation of the left ventricle combined with a mild to moderate increase in left ventricular wall thickness. Strength training is characterised by an elevation of both systolic and diastolic blood pressure. This pressure overload causes an increase in left ventricular wall thickness. This may or may not be accompanied by a slight raise in the left ventricular volume. However, the development of an endurancetrained heart and a strength-trained heart should not be considered an absolute concept. Both forms of training cause specific morphological changes in the heart, dependent on the type of sport. (Neth Heart J 2008;16:129-33.)     

Ultrasound markers of genetic pathology and early hemodynamic changes in human embryo

An increase in the nuchal translucency (NT) by more than 3 mm and ductus venosus reverse blood flow (DVRBF) in pregnancy weeks 11–14 are used as ultrasound markers (UMs) to determine the risk of genetic pathology and/or high probability of heart defects or severe maternal preeclampsia. A pathophysiological explanation for this phenomenon is the development of transient heart failure and increased afterload on the left myocardial ventricle in the embryo in this period. Earlier, it was shown that an increased left ventricular isovolumic relaxation time (LV IRT) reflects an increased systolic arterial pressure in fetal developmental delay. The mean LV IRT measured during an ultrasound study of 122 normally developing human embryos was 30 ± 2 ms. In 27 embryos with an increased NT and DVRBF, the mean LV IRT was 41 ± 3 ms (p < 0.01). This difference confirms the probable increased afterload on human embryo heart in this period of development.     

Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure.Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion. In contrast, the infarct area at 24 hr after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling.Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail.     

Percutaneous closure of a coronary fistula between the right coronary artery to the left atrium

We describe a case of a congenital coronary artery fistula of the right coronary artery draining into the left atrium in an eight-year-old boy. The initial diagnosis was made after the detection of a continuous cardiac murmur at the age of six years. Transthoracic echocardiography showed the right coronaric ostium dilatation, the site of drainage in the left atrium and left ventricle volume overload. Catheterization confirmed the diagnosis. The patient underwent percutaneous closure by PDA occluder device. Immediate post-closure angiograms showed complete occlusion of the fistula. The patient showed transient ischemic changes on ECG associated to an increase of plasmatic levels of the cardiac enzyme. ECG and cardiac enzyme were normal one week after the procedure.     

Chorioamnionitis and Patent Ductus Arteriosus: A Systematic Review and Meta-Analysis

Background

Chorioamnionitis has recently been reported as a risk factor for various neonatal diseases, including cerebral palsy, bronchopulmonary dysplasia, and necrotizing enterocolitis, but its effect on patent ductus arteriosus (PDA) is unclear. We performed a systematic review and meta-analysis to evaluate the effect of chorioamnionitis on PDA.

Methods

We searched PubMed, EMBASE, Cochrane Library, and KoreaMed databases using the terms: “intrauterine infection” or “maternal infection” or “antenatal infection” or “chorioamnionitis” or “placenta inflammation” or “placenta pathology” or “neonatal outcome” or “neonatal morbidity” or “PDA or patent ductus arteriosus” or “ductus arteriosus,” and “prematurity” or “very low birth weight infant.” Studies were included if they were randomized controlled trials, case–control studies, or cohort studies that included information relating to chorioamnionitis and PDA.

Results

Among 1,571 studies, a total of 23 studies (17,708 cases) were included in the meta-analysis to analyze the relationship between chorioamnionitis and PDA, except one study that only included PDA requiring surgical ligation. The association between chorioamnionitis and PDA was statistically significant (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.19, 1.72; P < 0.0001). In subgroup analysis, clinical chorioamnionitis was not associated with PDA (OR 1.28; 95% CI 1.00, 1.64, 1.790; P = 0.05), whereas histologic chorioamnionitis (OR 1.54; 95% CI 1.10, 2.15; P = 0.01) and chorioamnionitis diagnosed from both clinical and histologic findings (OR 1.75; 95% CI 1.07, 2.86; P = 0.03) showed significant associations with PDA. Chorioamnionitis did not increase the risk of PDA requiring surgical ligation (OR 1.23; 95% CI 0.69, 2.17; P = 0.48), and antenatal steroid use reduced the risk of PDA (OR 0.62; 95% CI 0.42, 0.90; P = 0.01) after chorioamnionitis.

Conclusions

The results from this meta-analysis support an association between maternal chorioamnionitis and PDA in offspring.