A multi-center trial on efficacy and safety of the LifeTech CeraFlexTM ASD occluder for transcatheter closure in patients with secundum atrial septal defects.

Background: The last decades have brought remarkable improvements in treatment strategy and occluder modification of secundum atrial septal defect (ASD) closure. Approval, efficacy and safety of ASD closure devices have previously been demonstrated. This study investigated the clinical efficacy and safety of the LifeTech CeraFlexTM ASD occluder for interventional closure of secundum ASD with a 6-month follow-up (FU). Methods: Procedure specific data was collected on patients considered for ASD closure with the CeraFlexTM occluder between April 2016 and December 2019 in three German centers. Efficacy and safety were assessed after device closure, at discharge, and at 6-month FU. Results: The primary endpoint (successful ASD closure without severe complications) was reached by 102/103 patients (99%). Device embolization occurred in two patients (one early and one late embolization). After early snare-retrieval of an embolized device, this ASD was closed surgically and in the other patient with late device embolization the defect was closed with a larger CeraFlexTM occluder. The secondary endpoint (clincal efficacy after 6 months) was reached by 94/98 patients since new onset of arrhythmia occurred in four patients. Three patients had withdrawn their study-participation and one patient had moderate residual shunt, but not related to the occluder. Incomplete right bundle branch block (iRBBB) was seen in 31 patients. At last FU only 17 patients had remaining iRBBB documenting effective volume unloading of the right ventricle. Conclusions: Catheter interventional closure of secundum ASDs with the CeraFlexTM ASD occluder was feasible, safe and effective in this study.

Non-cardiac comorbidities in adults with inherited and congenital heart disease: report from a single center experience of more than 800 consecutive patients.

BACKGROUND: As a result of improved surgical and therapeutical management, more than 90% of patients with congenital heart disease (CHD) reach adulthood. However, the natural course of CHD is complicated by noncardiac medical problems. Aim of the study was to evaluate noncardiac comorbidities in a contemporary cohort of adults with CHD (ACHD). METHODS: In a tertiary care center for ACHD, 821 consecutive patients, admitted to the outpatient clinic, were evaluated for clinically relevant noncardiac comorbidities. RESULTS: The consecutively included patients (age: range, 15-80 years; 56% female) represent all types and severity grades of acyanotic and cyanotic CHD. A considerable proportion of ACHD had significant noncardiac comorbidities, which have the potential to profoundly influence the natural course of the underlying disease. In 95.5%, relevant non-cardiac comorbidities were apparent, that could be related to 16 special medical fields as endocrinologic/metabolic disease, gastroenterology/hepatology, gynecology/obstetrics, angiology, orthopedics, neurology/psychiatry and others. Most frequently seen comorbidities were endocrine and metabolic disorders (43.97%). CONCLUSIONS: Non-cardiac comorbidities are increasingly common in ACHD. The data revealed non-cardiac comorbidities as they were presented in the cohort of ACHD seen in a tertiary center. The study proves that ACHD with significant non-cardiac comorbidities need multidisciplinary care by medical organ specialists, aside the congenital cardiologist, with a deep knowledge about congenital heart defects, the special effects of the organ disease on the particular heart defect and, how the heart defect may affect the course of the particular organ disease. The study may create the basis for the development of screening programs for comorbidities in ACHD as well as a multidisciplinary concept for diagnosis and treatment of concomitant disorders or for disease prevention. Particularly disease prevention may improve quality of life as well as the further fate of the affected patients.

Usefulness of Direct Oral Anticoagulants in Adult Congenital Heart Disease.

As thromboembolic events (TEE) are common in adults with congenital heart disease (ACHD), adequate oral anticoagulation for prophylaxis or treatment of TEE is important. Until now, mainly vitamin K antagonists have been used in these patients. The purpose of this study was to provide first data on the use of direct oral anticoagulants in ACHD. This prospective, observational, and longitudinal study included 102 consecutive ACHD, of whom 75 (37 women and 38 men; mean age 50 ± 13 years) could be analyzed. Most common CHD were pre-tricuspid shunts (n = 31; 41%), complex CHD (n = 16; 21%), left heart/aortic valve anomalies (n = 5; 6%), right-sided cardiac/pulmonary artery anomalies (n = 9; 13%), post-tricuspid shunts (n = 3; 4%), and others (n = 11; 15%). Five patients had cyanosis and 3 patients a Fontan circulation. Mean follow-up was 12 ± 11 months. Rivaroxaban was administered in 55 patients, apixaban in 13 and dabigatran in 7 patients for TEE prophylaxis in atrial arrhythmias (n = 57), stroke/transient ischemic attacks (n = 11), deep vein thrombosis (n = 4), pulmonary embolism (n = 1) and atrial thrombi (n = 3). Some patients had >1 indication for adequate oral anticoagulation. CHA2-DS2-VASc score was ≥ 2 in 23 (31%), and 9 (12%) had a HAS-BLED score ≥ 2. There were neither thrombotic or major bleeding events nor major side effects. In conclusion, direct oral anticoagulants appear to be safe and effective in ACHD. Long-term follow-up is needed to substantiate these findings.

Improved exercise performance and quality of life after percutaneous pulmonary valve implantation.

OBJECTIVE: Percutaneous pulmonary valve implantation (PPVI) has emerged as a new approach to treat patients with dysfunctional pulmonary valve conduits. Short- and midterm results have outlined hemodynamic improvements and increase in exercise performance. However, there is a lack of knowledge about quality of life at short term follow-up. PATIENTS AND METHODS: From July 2007 to March 2013, we investigated 59 patients (17 female; median age 22.8 years) undergoing PPVI in our institution. 46 had predominant pulmonary stenosis (PS) and 13 had predominant pulmonary regurgitation (PR). They answered the quality of life questionnaire (SF-36) and underwent a cardiopulmonary exercise test and Cardiovascular Magnetic Resonance before and 6 months after PPVI. RESULTS: Peak oxygen uptake improved significantly from 27.2 (18.9; 34.0) ml/min/kg to 29.2 (22.4; 35.3) ml/min/kg (p<.0001), and from 69.6 (55.9; 83.6) %predicted to 76.3 (67.9; 92.7) %predicted, respectively. Improvements were seen in both, the PS (71.9 to 78.3 %predicted; p<.0001) and PR (62.7 to 73.0 %predicted; p<.0001) group. Self-estimated quality of life was good already before PPVI but increased in almost all domains 6 months after PPVI in PS and PR group. Significant improvements developed in "physical function", "general health perception" and "health transition" in both groups, and "physical role functioning", "vitality" and "mental health" only in the PS group. CONCLUSIONS: In patients with dysfunctional pulmonary valve conduits exercise performance and quality of life improve substantially 6months after successful percutaneous pulmonary valve implantation.

Motor training of sixty minutes once per week improves motor ability in children with congenital heart disease and retarded motor development: a pilot study.

OBJECTIVE: Delay and impairment of motor development is reported in patients with congenital heart disease. This pilot study addressed the feasibility and effect of a low-dose motor training programme of 60 min once per week on motor ability in preschool children with congenital heart disease. PATIENTS AND METHODS: In all, 14 children--including four girls, in the age group of 4-6 years--with various types of congenital heart disease performed the motor developmental test MOT 4­6 before and after 3 months of a playful exercise programme of 60 min once a week. RESULTS: At baseline, the motor quotient ranged from normal to slightly impaired (median 92.0; Quartile 1: 83.75; Quartile 3: 101.25). After intervention, motor quotient did not change significantly for the entire group (95.0 (88.0, 102.5); p50.141). However, in the subgroup of nine children with retarded motor development at baseline (motor quotient lower 100), seven children had an improved motor quotient after 3 months of intervention. In this subgroup, motor quotient increased significantly (p50.020) by 5%. CONCLUSIONS: Overall, a short intervention programme of 60 min only once a week does not improve motor ability in all children with congenital heart disease. However, those with retarded motor development profit significantly from this low-dose intervention.

Differences in centromere positioning of cycling and postmitotic human cell types.

Centromere positioning in human cell nuclei was traced in non-cycling peripheral blood lymphocytes (G0) and in terminally differentiated monocytes, as well as in cycling phytohemagglutinin-stimulated lymphocytes, diploid lymphoblastoid cells, normal fibroblasts, and neuroblastoma SH-EP cells using immunostaining of kinetochores, confocal microscopy and three-dimensional image analysis. Cell cycle stages were identified for each individual cell by a combination of replication labeling with 5-bromo-2'-deoxyuridine and immunostaining of pKi67. We demonstrate that the behavior of centromeres is similar in all cell types studied: a large fraction of centromeres are in the nuclear interior during early G1; in late G1 and early S phase, centromeres shift to the nuclear periphery and fuse in clusters. Peripheral location and clustering of centromeres are most pronounced in non-cycling cells (G0) and terminally differentiated monocytes. In late S and G2, centromeres partially decluster and migrate towards the nuclear interior. In the rather flat nuclei of adherently growing fibroblasts and neuroblastoma cells, kinetochores showed asymmetrical distributions with preferential kinetochore location close either to the bottom side of the nucleus (adjacent to the growth surface) or to the nuclear upper side. This asymmetrical distribution of centromeres is considered to be a consequence of chromosome arrangement in anaphase rosettes.