Maternal plasma mRNA species in fetal heart defects: a potential for molecular screening.

OBJECTIVE: To verify the hypothesis that aberrant placental mRNA genes related to cardiogenesis can be detected in maternal plasma at the second trimester of pregnancy. METHODS: NanoString technology was used to identify aberrant genes, comparing 39 women carrying a fetus with a congenital heart defect (CHD) to 31 controls at 19-24 weeks of gestation. The genes with differential expression were subsequently tested using real time polymerase chain reaction. Linear discriminant analysis (LDA) was used to combine all the mRNA species with discriminant ability for CHD. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated. RESULTS: Six genes with differential expression, namely FALZ, PAPP-A, PRKACB, SAV1, STK4 and TNXB2, were found. The ROC curve yielded a detection rate of 66.7% at a false positive rate of 10%. A higher discriminant score (>75(th) centile) was reached for 14 CHD cases (82.4%) and only 1 control (5.8%). Two cases (11.8%) of heart rhythm disorders also yielded a discriminant score value >75(th) centile. CONCLUSION: These data represent a step forward in the screening of CHDs. Additional studies are needed to detect more mRNAs with discriminant ability and to move the first trimester screening.

Turner syndrome strategies to improve care outcomes--cardiac evaluation using new imaging techniques.

Turner syndrome (TS) is at high risk for congenital heart diseases (CHD), aortic dilatation (AoDil) and dissection. New imaging techniques such as MRI have revealed the presence of vascular anomalies (VA) undetected at echo. MR angiography has shown a high prevalence of aortic and venous anomalies. The VA often coexist and interact to increase the risk of premature death in adulthood. AoDil and VA have been found also in asymptomatic individuals with no predisposing factors, but the prevalence is still unknown. We evaluated 100 TS subjects (15-35 yrs) with no aortic CHD at echocardiography with transthoracic MRA; 42 of them showed VA and 58 did not. Aortic diameters were indexed on BSA. At the sinuses of Valsalva a higher prevalence of AoDil was found in subjects with VA than without; 57% of them showed AoDil. The presence of VA (elongation of the transverse arch, bovine arch, left superior vena cava, PAPVD etc.) increased their relative risk of AoDil by more than 2 times. Excluding BSA influence, a severe phenotype influenced positively ascending AoDil. New imaging techniques enhance our ability to provide a prognosis for their adult age and in particular before they seek to become pregnant.

Prediction of neonatal coarctation of the aorta at fetal echocardiography: a scoring system.

INTRODUCTION: Coarctation of the aorta (CoA) is common and can lead to neonatal emergency. Despite its burden, antenatal detection of this condition remains inaccurate. OBJECTIVE: To evaluate the diagnostic performance of fetal echocardiography and to design a scoring system for risk stratification of CoA in suspected cases. DESIGN: A retrospective cohort study. SETTING: S. Orsola Hospital, Bologna, Italy. POPULATION: About 140 fetuses referred for suspected CoA to our tertiary center in a 9-year period. METHODS: The following parameters were systematically obtained at fetal echocardiography: ventricular disproportion, great vessels asymmetry, transverse aortic arch hypoplasia, flow turbulence, and Z-scores of the ascending aorta and of the aortic isthmus. Associated anomalies were recorded, if present. When CoA was not confirmed at birth, neonates were followed up for 12 months to identify also a tardive onset of this condition. MAIN OUTCOME MEASURES: The primary outcome was the presence of COA after birth. RESULTS: 108 fetuses were eligible for the purpose of the study. CoA was confirmed postnatally in 55 neonates (50.9%). Arch hypoplasia yielded the highest correlation with CoA. The affected neonates presented also significantly lower Z scores of the ascending aorta and of the aortic isthmus. Earlier gestational age at referral was positively correlated with neonatal CoA. An odds ratio-based multiparametric model was designed to build a scoring system (AUC 0.89). CONCLUSION: In our cohort, no single ultrasound parameter was sufficiently accurate to predict postnatal CoA. The scoring system permitted a better identification of the affected fetuses.

Identification of circulating placental mRNA in maternal blood of pregnancies affected with fetal congenital heart diseases at the second trimester of pregnancy: implications for early molecular screening.

OBJECTIVE: To investigate whether a significantly aberrant expression of circulating placental mRNA genes related with cardiogenesis can be detected at the second trimester of pregnancy. METHODS: The study was performed in two stages. First stage (development model group): match of 14 placental tissues at delivery of fetuses with congenital heart disease versus 20 controls. Second stage (validation model group): mRNA amplification of abnormal expressed genes in maternal blood samples from 26 women bearing a fetus with a congenital heart disease matched with 28 controls. RESULTS: We identified four functional categories of genes possibly involved in abnormal heart development: cardiac morphogenesis: tenascin, thioredoxin, salvador homolog 1 protein; extracellular matrix (ECM) and valvular tissue biosynthesis; placental-associated plasma protein, collagen, type I, alpha 2, fibulin-1, heparanase, procollagen-proline, 2-oxoglutarate 4-dioxygenase, alpha polypeptide II, Jumonji, AT rich interactive domain 1B RBP2-like; normal contractile activity: actinin, alpha 4, fascin homolog 1, actin-bundling protein; and congestive heart failure. CONCLUSION: Altered placental genetic expression was found at term delivery in affected fetuses. The aberration was also confirmed in maternal blood at the second trimester of women bearing a fetus with congenital heart disease. Sensitivity for the most aberrant genes ranged between 42% and 95% at a false positive rate (FPR) of 10%.

Dilated cardiomyopathy presenting in childhood: aetiology, diagnostic approach, and clinical course.

OBJECTIVE: To determine the outcome of dilated cardiomyopathy presenting in childhood and the features that might be useful for prognostic stratification. METHODS: Retrospective study of 41 consecutive children affected by dilated cardiomyopathy - aged 0-14 years; median 33.4 plus or minus 49.25 - between 1993 and 2008. We reviewed the medical history to determine age at diagnosis, family history, previous viral illness, aetiology, symptoms and signs at presentation, treatment, and outcome. The diagnosis was made on the basis of cardiomegaly and evidence of poor left ventricular function by echocardiography. We also carried out a metabolic evaluation including blood lactate, pyruvate, carnitine, amino acids, urine organic acids, assessment of respiratory chain enzymes, and analysis of histopathological material. Survival curves were constructed by the Kaplan-Meier method. RESULTS: Follow-up ranged from 10 days to 162 months - median 45.25 plus or minus 41.15 months. Freedom from death or cardiac transplantation was 68.3% at 5 years. The primary end-point of death/cardiac transplantation was associated with the need for intravenous inotropic support. A trend towards a poorer prognosis was found for age at diagnosis of more than 5 years and for a metabolic aetiology of dilated cardiomyopathy. For the children affected by cardiomyopathy as part of a multi-system involvement, mortality was 50%. CONCLUSIONS: In children, dilated cardiomyopathy is a diverse disorder with outcomes that depend on cause, age, and cardiac failure status at presentation. Overt cardiac failure at presentation is a major prognostic factor for death or cardiac transplantation. Older age at presentation and metabolic aetiology may be associated with a poorer prognosis.

[Atypical Kawasaki disease with acute cholestasis and early coronary involvement at onset in an adolescent]. / Malattia di Kawasaki atipica esordita con colestasi acuta ed interessamento coronarico precoce in un adolescente.

Kawasaki disease is an acute febrile illness of childhood that affects usually children younger than 5 years of age. The diagnosis is based on typical clinical features. Atypical or incomplete forms of Kawasaki disease can be observed in almost 20% of patients and at onset is a clinical challenge leading to diagnostic and therapeutic delays with higher risk of coronary abnormalities. We report the case of a 13-year-old boy who presented with febrile cholestasis, abdominal pain and early coronary anomalies that was diagnosed with Kawasaki disease. Atypical findings of our case at onset were the age, the clinical presentation and the timing of appearance of coronary anomalies. A high index of suspicion of Kawasaki disease should be maintained in patients presenting with febrile cholestatic jaundice.

Heart transplantation in infants with idiopathic hypertrophic cardiomyopathy.

Whereas it is well known that idiopathic HCM can present in newborns and infants, little information is available on HT in this very young age group. We report a series of 17 infants with idiopathic HCM, including two neonates with rapidly progressive severe HF for whom HT was necessary. When HF manifests in a newborn/infant with idiopathic HCM and extreme cavity size reduction, the possibility of a rapidly progressive clinical course should be anticipated and HT may become the only available therapeutic solution.

Correlations of phenotype and genotype in relation to morphologic remodelling of the aortic root in patients with Turner's syndrome.

BACKGROUND: Patients with Turner's syndrome are at risk of aortic dilation and dissection. Currently, it is not known whether such dilation is related to associated cardiovascular abnormalities, or to the genetic anomaly itself. METHODS: We studied echocardiographically 107 patients with genetically proven Turner's syndrome, with heterogeneous underlying karyotypes, and without associated cardiac lesions. Their average age was 19.6 plus or minus 8.4 years. We compared the finding with those from 71 age-matched healthy female volunteers. The diameter of the aorta was measured at the level of the basal attachments of the aortic valvar leaflets, the sinuses of Valsalva, the sinutubular junction, and its ascending component. RESULTS: Compared to control subjects, the patients with Turner's syndrome had larger diameters of the aorta at the level of the sinuses of Valsalva, at 23.4+/-4.8 versus 25.5+/-4.1 millimetres (p = 0.0014), the sinutubular junction, at 19.9+/-3.8 versus 23.3+/-4.1 millimetres (p < 0.0001), and the ascending aorta, at 22.3+/-4.9 versus 24.6+/-4.4 millimetres (p = 0.0011). Dilation of the sinutubular junction, found in just over one-quarter of the patients, was more common than dilation of the ascending aorta, the latter found in less than one-tenth. The patients with Turner's syndrome, therefore, presented with remodelling of the aortic root, with relative dilation of the sinutubular junction. The underlying karyotype influenced both the dimensions of the sinutubular junction (p = 0.0054), and the ascending aorta (p = 0.0064), so that patients with the karyotype 45X had larger aortas. The karyotype was the strongest predictor by multivariate analysis for dilation at both these sites (p = 0.0138 and 0.0085, respectively). CONCLUSIONS: Dilation at the sinutubular junction is frequent in patients with Turner's syndrome, and is more common than dilation of the ascending aorta. The syndrome is associated with a remodelling of the aortic root, with prominent dilation of the sinutubular junction. There seems to be a relation between aortic dilation and the underlying genotype.

Dilated cardiomyopathy in a pediatric population: etiology and outcome predictors - a single-center experience.

AIM: The aim of the study was to assess predictors of outcome in patients hospitalized for dilated cardiomyopathy (DCM) and severe left ventricular dysfunction. Patients & methods: 83 pediatric patients hospitalized for heart failure due to DCM with coexistent left ventricular dysfunction were enrolled. RESULTS: Overall, 5-year survival free from heart transplantation was 69.8%. Normalization of left ventricular function was achieved in 39.8% of patients during follow-up: younger age, less necessity of inotropic support and other than idiopathic DCM predicted left ventricular function, while familial history for cardiac disease or sudden death and inotropic support during hospitalization were associated with poorer outcome. CONCLUSION: Almost 40% of patients with DCM experienced a complete normalization of cardiac function. Outcome was extremely variable according to the type of DCM.

Heart transplantation in hypertrophic cardiomyopathy.

Heart transplantation (HT) is the sole therapeutic option for selected patients with hypertrophic cardiomyopathy (HC) and refractory heart failure. However, the results of HT have not been systematically investigated in HC. We assessed the pathophysiologic profile of HT candidates and the outcome after transplantation in 307 patients with HC consecutively evaluated at our tertiary referral center from 1987 to 2005; follow-up was 9.9+8.2 years. Outcome of recipients with HC was compared with that of 141 patients who underwent transplantation for idiopathic dilated cardiomyopathy at our center over the same period. Of 21 patients with HC who entered the transplantation list, 20 had end-stage evolution with systolic dysfunction and 1 had an extremely small left ventricular cavity with impaired filling and recurrent cardiogenic shock during paroxysmal atrial fibrillation. Of 33 study patients with HC who showed end-stage evolution during follow-up, the 23 who were included on the waiting list or died from refractory heart failure (2 patients) were significantly younger than the 10 patients who remained clinically stable (37+/-14 vs 57+/-17 years, p=0.004). Of the 21 HT candidates, 18 underwent transplantation during follow-up. In heart transplant recipients, 7-year survival rate was 94% and not different from that of the 141 patients who received transplants for idiopathic dilated cardiomyopathy (p=0.66). In conclusion, long-term outcome after HT in patients with HC is favorable and similar to that of patients with idiopathic dilated cardiomyopathy. In patients with end-stage HC, young age is associated with more rapid progression to refractory heart failure.

Levels of Circulating mRNA for the Tenascin-X (TNXB) Gene in Maternal Plasma at the Second Trimester in Pregnancies with Isolated Congenital Ventricular Septal Defects.

OBJECTIVE: Maternal plasma is a source of circulating placental nucleic acids. In this study, we validated previous observations on abnormal levels of circulating messenger RNA (mRNA) for the tenascin-X gene in pregnancies with ventricular septal defects in the second trimester of pregnancy. METHODS: This was a bicentric retrospective study conducted from March 2016 to July 2017. Real-time polymerase chain reaction was used to identify abnormally expressed genes, comparing ten women carrying a euploid fetus with ventricular septal defects to 30 controls at 19-24 weeks of gestation. The univariable analysis was used to determine whether the mean mRNA for the tenascin-X gene values would differ from the expected values for the controls. RESULTS: mRNA for tenascin-X gene values was higher in ventricular septal defects, 4.38 ± 3.01 versus 1.00 ± 0.80. The result was still significant even after adjustment for gestational age. CONCLUSIONS: These data confirm previous studies on the specific association of mRNA species and type of congenital heart defect and confirm that ventricular septal defects are associated with abnormal mRNA for the tenascin-X gene. The positive predictive value of this molecular marker in the general population should be assessed through prospective studies.

Multimodality imaging, single center, cross-sectional study in adolescents or young adults with repaired tetralogy of Fallout.

BACKGROUND: Proper integration of multiple imaging modalities in the routine follow-up of patients with repaired tetralogy of Fallout (TOF) is poorly supported by data. We report our single center comparative study between cardiac magnetic resonance (CMR) and echocardiography to assess equipoise in the clinical utility of these two imaging methods in an unselected consecutive cohort of TOF patients referred to our outpatient clinic. MATERIAL AND METHODS: In this cross-sectional study, repaired TOF patients who underwent CMR and echocardiography within a 4-week period between 2010 and 2011 at our Center were included. Linear regression was used to analyze degree of inter modality correlation. A prediction model tested the association between functional data/probrain natriuretic peptide (Pro-BNP) with CMR. RESULTS: Fifty patients were included in the study (mean age 31 ±â€Š18 years). The best predictors of right ventricle (RV) ejection fraction at CMR were tricuspid anular plane systolic excursion (tricuspid valve anular plane systolic excursion, R 0.37, P < 0.0001) and RV peak S-wave velocity (R 0.40, P < 0.001). Pro-BNP levels did present weak correlation with New York Heart Association functional class (R 0.31, P < 0.002) and QRS duration (R 0.32, P < 0.002) and a moderate correlation with right atrium area at CMR (R 0.46, P < 0.0001). CONCLUSION: We found limited correlation between the two imaging modalities in the evaluation of RV after intracardiac repair of TOF. Pro-BNP level presents moderate correlation with right atrium area measured with echocardiography. Serial CMR evaluations are needed in this patient population, but they may be interchanged by routine echocardiography in particular in patients with normal or stable echocardiographic parameters.

Circulating mRNA in Maternal Plasma at the Second Trimester of Pregnancy: A Possible Screening Tool for Cardiac Conotruncal and Left Ventricular Outflow Tract Abnormalities.

OBJECTIVE: Maternal plasma is a source of circulating placental nucleic acids. This study was designed to detect aberrantly expressed placental mRNA genes circulating in the maternal plasma of pregnancies affected with fetal conotruncal anomalies (CNTRA) and left-ventricular outflow tract (LVOT) obstruction in the second trimester of pregnancy. METHODS: This was a retrospective monocentric study conducted from 1 Jan 2016 to 31 Dec 2016. NanoString technology was used to identify aberrantly expressed genes, comparing 36 women carrying a fetus with CNTRA or LVOT obstruction to 42 controls at 19-24 weeks of gestation. The genes with differential expression were subsequently tested using real-time polymerase chain reaction. Linear discriminant analysis was used to combine all the mRNA species with discriminant ability for CNTRA and LVOT obstruction. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated for the two affected groups versus controls. RESULTS: Three genes with differential expression, namely MAPK1, IQGAP1 and Visfatin were found. The ROC curves yielded detection rates of 60 and 62.5% at a false-positive rate of 5% for CNTRA and LVOT, respectively. CONCLUSIONS: These data suggested that molecular screening of CNTRA and LVOT obstruction in the second trimester is feasible. Prospective studies are needed to test the discriminant ability of these genes and to calculate the predictive positive value in the general population.

Recurrent Stroke after Transcatheter PFO Closure in Cryptogenic Stroke or Tia: Long-Term Follow-Up.

BACKGROUND: There are few data on the mechanism of recurrent neurological events after transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke or TIA. METHODS: We retrospectively reviewed PFO closure procedures for the secondary prevention of cryptogenic stroke/TIA performed between 1999 and 2014 in Bologna, Italy. RESULTS: Written questionnaires were completed by 402 patients. Mean follow-up was 7 ± 3 years. Stroke recurred in 3.2% (0.5/100 patients-year) and TIA in 2.7% (0.4/100 patients-year). Ninety-two percent of recurrent strokes were not cryptogenic. Recurrent stroke was noncardioembolic in 69% of patients, AF related in 15% of patients, device related in 1 patient, and cryptogenic in 1 patient. AF was diagnosed after the procedure in 21 patients (5.2%). Multivariate Cox's proportion hazard model identified age ≥ 55 years at the time of closure (OR 3.16, p=0.007) and RoPE score < 7 (OR 3.21, p=0.03) as predictors of recurrent neurological events. CONCLUSION: Recurrent neurological events after PFO closure are rare, usually noncryptogenic and associated with conventional vascular risk factors or AF related. Patients older than 55 years of age and those with a RoPE score < 7 are likely to get less benefit from PFO closure. After transcatheter PFO closure, lifelong strict vascular risk factor control is warranted.

Transcatheter patent foramen ovale closure mitigates aura migraine headaches abolishing spontaneous right-to-left shunting.

BACKGROUND: Patent foramen ovale (PFO) has been implicated in the etiology of migraine headache with aura (MHA), but the mechanisms that link right-to-left (R-to-L) shunt to MHA are unclear, and the reports on the efficacy of transcatheter PFO closure on MHA prevention are scarce. METHODS: We reviewed the clinical records of 131 consecutive patients who underwent successful transcatheter PFO closure at our institution at a mean age of 45 +/- 13 years because of cryptogenic stroke. Of the 131 patients, 35 (27%) had a diagnosis of MHA made by the primary care physician or the referring neurologist. Migraine headache with aura incidence and severity were assessed by using Migraine Disability Assessment (MIDAS) questionnaire. Presence and magnitude of R-to-L shunt were assessed in all patients by means of transesophageal echocardiography and also by means of transcranial Doppler (TCD) in the last 50 patients (38%). RESULTS: Patients with MHA had a higher prevalence of thrombophilia (P = .007), a more complex atrial septal anatomy (P = .001), and they also had higher prevalence of spontaneous R-to-L shunt and of spontaneous large shunt, both at transesophageal echocardiography (P = .015, and .028, respectively) and at TCD (P = .036, and .038, respectively). After the procedure, 32 (91%) of 35 patients had either complete resolution or significant improvement in their MHA. At a mean follow-up of 1.7 +/- 1.3 years, MHA disappeared completely in 29 (83%) of 35 patients. Of the remaining 6 patients, 3 patients (8%) had an improvement of > or = 2 grades in the incidence and severity of MHA, 2 patients did not show any improvement of their MHA, whereas 1 patient reported a severe relapse of MHA about 1 year after the procedure. CONCLUSIONS: In patients with PFO, MHA is associated with spontaneous large R-to-L shunt and thrombophilic conditions. Transcatheter defect closure seems to be an effective and safe means to treat MHA in patients with PFO.

Determinants of cardiopulmonary functional improvement after transcatheter atrial septal defect closure in asymptomatic adults.

OBJECTIVES: We sought to evaluate the course of cardiopulmonary function after transcatheter atrial septal defect (ASD) closure and to identify the physiopathologic mechanisms leading to this change. BACKGROUND: Conflicting reports exist on cardiopulmonary functional improvement in asymptomatic adults after transcatheter closure of a secundum ASD. METHODS: Thirty-two consecutive adults (13 males; age 42.6 +/- 16.7 years) underwent maximal cardiopulmonary exercise testing and transthoracic echocardiography both on the day before and six months after transcatheter ASD closure. Mean pulmonary artery pressure, pulmonary to systemic flow ratio (Qp/Qs), and ASD diameter were measured before closure. RESULTS: Peak oxygen uptake (Vo(2)) (p < 0.001), peak oxygen pulse (p = 0.0027), and vital capacity (p = 0.0086) improved after ASD closure, although peak heart rate did not. A significant correlation was found between peak Vo(2) improvements and Qp/Qs (p = 0.0013). Left ventricular ejection fraction (LVEF) (p < 0.0001) and left ventricular end-diastolic diameter (LVEDD) (p < 0.0001) significantly increased after six months, although left ventricular end-systolic diameter did not. Right ventricular long- and short-axis dimensions decreased (both p < 0.0001). Peak Vo(2) and of peak oxygen pulse improvements correlated to both LVEF (p = 0.0009 and 0.0019, respectively) and LVEDD (p < 0.0001 and 0.032, respectively) increments. The decrease of both long- and short-axis right ventricular dimensions positively correlated to both LVEF and LVEDD improvements. The improvement in LVEF correlated to Qp/Qs (p = 0.0026). CONCLUSIONS: Transcatheter ASD closure leads to a significant improvement in cardiopulmonary function within six months, via an increase in peak oxygen pulse. An increase in both left ventricular stroke volume and cardiac output due to a positive ventricular interaction is the mechanism leading to improved peak Vo(2).

Changed outcomes of fetuses with congenital heart disease: new Italian Multicentre study.

OBJECTIVES: To analyse the outcomes of fetuses with congenital heart disease between 2000 and 2005 in comparison to a previous multicentre study regarding the period 1983-1996. PARTICIPANTS AND METHODS: Data of seven centres were prospectively collected, the inclusion criteria being a confirmed fetal diagnosis after birth or at autopsy and a known follow-up, for at least 6 months after birth. Data of 649 fetuses, median age at diagnosis 24 weeks' gestation (15-37), 340/649 (52.4%) diagnosed before 24 weeks, were analysed. RESULTS: Sixty seven and 59 cases had chromosomal or extracardiac anomalies (10.3 and 9.1%). Termination of pregnancy was chosen in 21.6% of cases versus 28.9% in the previous study, being significantly lower in cases with early diagnosis (P <0.001). Out of 509 fetuses continuing pregnancy, 23 died in utero (4.5%) and 110 (21.1%) postnatally, versus 43% in the previous study (P <0.0017). Total surgical/postprocedure death occurred in 20.6% (59/287 infants) versus 37% previously (P <0.003), 67 infants being premature and 35 with associated chromosomal or extracardiac anomalies. The current overall mortality rate was higher in cases with chromosomal or extracardiac anomalies (59.5 and 51.35%, respectively, whereas it was 20.1% in isolated congenital heart disease). Overall current survival was 376 of 509 (73.9%) versus 45% in the previous study (P <0.0001). CONCLUSION: Our data show a reduced overall and surgical mortality, with respect to our previous study, resulting from resulting from an improved perinatal management and treatment of affected fetuses in the more recent era.

Recovery kinetics of oxygen uptake is prolonged in adults with an atrial septal defect and improves after transcatheter closure.

BACKGROUND: In adults with an atrial septal defect (ASD) transcatheter closure leads to an improvement of peak oxygen uptake (VO2), but the kinetics of recovery of VO2 after maximal exercise in this patient population and the impact of transcatheter ASD closure have never been investigated. METHODS: Twenty consecutive patients underwent a maximal cardiopulmonary exercise test both the day before and 6 months after transcatheter ASD closure. For comparison, an age- and sex-matched group consisting of 53 healthy adults was built. The constant decay of VO2, CO2 production (VCO2), minute ventilation (VE), and heart rate (HR), expressed as the first-degree slope of a single linear relation, were calculated for the first minute of recovery. RESULTS: Patients with an ASD had a prolonged VO2 slope (P =.0012), VCO2 slope (P =.0003), and VE slope (0.013) when compared with control subjects. Six months after transcatheter ASD closure, significant improvements of VO2 slope (P =.0043) and of VCO2 slope (P =.0022) were recorded, so that no difference was found when compared with those of the control group (P =.1 and P =.06, respectively). The VE slope and HR slope did not change after closure. A significant association between VO2 slope and peak VO2 in the group of patients with ASD was shown by the Spearman correlation, both before (r = 0.67, P =.0012) and after ASD closure (r = 0.71, P =.0004). CONCLUSIONS: A limited cardiopulmonary reserve in adults with no symptom who have an ASD appears to affect not only maximal exercise responses but also the recovery phase. Transcatheter ASD closure induces a significant improvement of the ability of recovering from maximal exercise and eliminates the difference with a healthy population.

Comparison of results of percutaneous closure of patent foramen ovale for paradoxical embolism in patients with versus without thrombophilia.

We investigated the efficacy of transcatheter patent foramen ovale (PFO) closure to prevent recurrent cerebral ischemic events in patients who did and those who did not have thrombophilia. Patients who have a PFO and an associated thrombophilia may have an increased risk of cerebral ischemic events. Seventy-two consecutive patients (mean age 42 +/- 13 years) underwent percutaneous PFO closure because of a cerebral stroke (51%) or a transient ischemic attack (49%). A thrombophilia was found in 20 patients (28%). A large right-to-left shunt through the PFO was found in 44 patients (61%) and an atrial septal aneurysm was found in 39 (54%). After the first event, 18 of 20 patients (90%) with a thrombophilia received oral anticoagulation. Before closure, patients who had a thrombophilia also had a higher rate of recurrences than patients who did not (p <0.0001), despite a similar follow-up (p = 0.14) and regardless of shunt entity (p = 0.59), presence of an atrial septal aneurysm (p = 0.98), and a prevalence of cardiovascular risk factors (p = 0.44). PFO closure was successful in all patients. Five patients (8%) had a residual shunt at 6 months. At 20 +/- 11 months after PFO closure, 3 recurrent events occurred (4%), and the recurrence rate was similar in patients who did and those who did not have a thrombophilia (p = 0.25). Thus, in patients who have a cryptogenic stroke, the association of a PFO with a thrombophilia significantly increases the risk of recurrences. Thus, transcatheter PFO closure is effective for preventing recurrences in patients who have a thrombophilia.

Transcatheter closure of the patent ductus arteriosus with new-generation devices: comparative data and follow-up results.

BACKGROUND: Many devices currently used for the closure of the patent ductus arteriosus are claimed to be safe and cost-effective, but only few data exist with respect to the gold standard of the Rashkind occluder. The aim of this study was to assess the efficacy and safety of three new different devices and to compare the results to those of a control group of patients carrying a Rashkind occluder. This should provide the basis for further cost-analysis studies. METHODS: The records of all patients who underwent closure of the patent ductus at our Institution from April 1989 to May 2001 were reviewed. Eighty patients (median age 10.3 years, median weight 27.6 kg) were treated (25 with a Rashkind device, 11 with Duct-Occlud coils, 35 with Cook detachable coils, 9 with the Amplatzer system). RESULTS: Kaplan-Meyer estimates of long-term complete occlusion of the ductus showed, compared to the Rashkind device, a significant improvement for the Cook and Amplatzer (p = 0.025 and p = 0.003, respectively) devices but not for the Duct-Occlud coils (p = 0.165). One patient of the Duct-Occlud group (9%) and 3 with the Rashkind device (12%) featured a significant residual shunt and needed a second intervention. The complication rate was 4% for the Rashkind occluder, 5% for the Cook coils, 9% for the Duct-Occlud system, and 11% for the Amplatzer device (p > 0.05). CONCLUSIONS: The new devices are as safe as the Rashkind occluder and provide effective treatment. The Cook coils and the Amplatzer occluder offer better results compared to the Rashkind and Duct-Occlud devices.