Paediatric Cardiolgoy – Pubmed results

Related Articles

Pediatric catheter ablation at the beginning of the 21st century: results from the European Multicenter Pediatric Catheter Ablation Registry 'EUROPA'.

Europace. 2020 Nov 23;:

Authors: Krause U, Paul T, Bella PD, Gulletta S, Gebauer RA, Paech C, Kubus P, Janousek J, Ferrari P, De Filippo P

Abstract
AIMS: Contemporary data from prospective multicentre registries on catheter ablation in pediatric patients are sparse. Aim of the European Pediatric Catheter Ablation Registry EUROPA was to contribute data to fill this gap of knowledge.
METHODS AND RESULTS: From July 2012 to June 2017, data on catheter ablation in pediatric patients (≤18 years of age) including a 1-year follow-up from five European pediatric EP centres were collected prospectively. A total of 683 patients (mean age 12.4 ± 3.9 years, mean body weight 50.2 ± 19 kg) were enrolled. Target tachycardia was WPW/atrioventricular-nodal re-entrant tachycardia (AVRT) in 380 (55.7%) patients, AVNRT in 230 (33.8%) patients, ventricular tachycardia (VT) in 24 (3.5) patients, focal atrial tachycardia (FAT) in 20 (2.9%) patients, IART in 14 (2%) patients, and junctional ectopic tachycardia in 3 (0.45) patients. Overall procedural success was 95.6%. Compared with all other substrates, success was significantly lower in FAT patients (80%, n = 16, P = 0.001). Mean procedure duration was 136 ± 67 min and mean fluoroscopy time was 4.9 ± 6.8 min. Major complications occurred in 0.7% of the patients. No persisting AV block requiring permanent pacing was reported. At 1-year follow-up (605/683 patients, 95%), tachycardia recurrence was reported in 7.8% of patients. Recurrence after VT ablation (33%) was significantly higher (P = 0.001) than after ablation of all other substrates.
CONCLUSION: The present study proves overall high efficacy and safety of catheter ablation of various tachycardia substrates in pediatric patients. Of note, complication rate was exceptionally low. Long-term success was high except for patients after VT ablation.

PMID: 33227133 [PubMed - as supplied by publisher]

Related Articles

Risk factors during first 1,000 days of life for carotid intima-media thickness in infants, children, and adolescents: A systematic review with meta-analyses.

PLoS Med. 2020 Nov;17(11):e1003414

Authors: Epure AM, Rios-Leyvraz M, Anker D, Di Bernardo S, da Costa BR, Chiolero A, Sekarski N

Abstract
BACKGROUND: The first 1,000 days of life, i.e., from conception to age 2 years, could be a critical period for cardiovascular health. Increased carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis. We performed a systematic review with meta-analyses to assess (1) the relationship between exposures or interventions in the first 1,000 days of life and CIMT in infants, children, and adolescents; and (2) the CIMT measurement methods.
METHODS AND FINDINGS: Systematic searches of Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and Cochrane Central Register of Controlled Trials (CENTRAL) were performed from inception to March 2019. Observational and interventional studies evaluating factors at the individual, familial, or environmental levels, for instance, size at birth, gestational age, breastfeeding, mode of conception, gestational diabetes, or smoking, were included. Quality was evaluated based on study methodological validity (adjusted Newcastle-Ottawa Scale if observational; Cochrane collaboration risk of bias tool if interventional) and CIMT measurement reliability. Estimates from bivariate or partial associations that were least adjusted for sex were used for pooling data across studies, when appropriate, using random-effects meta-analyses. The research protocol was published and registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42017075169). Of 6,221 reports screened, 50 full-text articles from 36 studies (34 observational, 2 interventional) totaling 7,977 participants (0 to 18 years at CIMT assessment) were retained. Children born small for gestational age had increased CIMT (16 studies, 2,570 participants, pooled standardized mean difference (SMD): 0.40 (95% confidence interval (CI): 0.15 to 0.64, p: 0.001), I2: 83%). When restricted to studies of higher quality of CIMT measurement, this relationship was stronger (3 studies, 461 participants, pooled SMD: 0.64 (95% CI: 0.09 to 1.19, p: 0.024), I2: 86%). Only 1 study evaluating small size for gestational age was rated as high quality for all methodological domains. Children conceived through assisted reproductive technologies (ART) (3 studies, 323 participants, pooled SMD: 0.78 (95% CI: -0.20 to 1.75, p: 0.120), I2: 94%) or exposed to maternal smoking during pregnancy (3 studies, 909 participants, pooled SMD: 0.12 (95% CI: -0.06 to 0.30, p: 0.205), I2: 0%) had increased CIMT, but the imprecision around the estimates was high. None of the studies evaluating these 2 factors was rated as high quality for all methodological domains. Two studies evaluating the effect of nutritional interventions starting at birth did not show an effect on CIMT. Only 12 (33%) studies were at higher quality across all domains of CIMT reliability. The degree of confidence in results is limited by the low number of high-quality studies, the relatively small sample sizes, and the high between-study heterogeneity.
CONCLUSIONS: In our meta-analyses, we found several risk factors in the first 1,000 days of life that may be associated with increased CIMT during childhood. Small size for gestational age had the most consistent relationship with increased CIMT. The associations with conception through ART or with smoking during pregnancy were not statistically significant, with a high imprecision around the estimates. Due to the large uncertainty in effect sizes and the limited quality of CIMT measurements, further high-quality studies are needed to justify intervention for primordial prevention of cardiovascular disease (CVD).

PMID: 33226997 [PubMed - as supplied by publisher]

Related Articles

A phenome-wide association study of 26 mendelian genes reveals phenotypic expressivity of common and rare variants within the general population.

PLoS Genet. 2020 Nov 23;16(11):e1008802

Authors: Tcheandjieu C, Aguirre M, Gustafsson S, Saha P, Potiny P, Haendel M, Ingelsson E, Rivas MA, Priest JR

Abstract
The clinical evaluation of a genetic syndrome relies upon recognition of a characteristic pattern of signs or symptoms to guide targeted genetic testing for confirmation of the diagnosis. However, individuals displaying a single phenotype of a complex syndrome may not meet criteria for clinical diagnosis or genetic testing. Here, we present a phenome-wide association study (PheWAS) approach to systematically explore the phenotypic expressivity of common and rare alleles in genes associated with four well-described syndromic diseases (Alagille (AS), Marfan (MS), DiGeorge (DS), and Noonan (NS) syndromes) in the general population. Using human phenotype ontology (HPO) terms, we systematically mapped 60 phenotypes related to AS, MS, DS and NS in 337,198 unrelated white British from the UK Biobank (UKBB) based on their hospital admission records, self-administrated questionnaires, and physiological measurements. We performed logistic regression adjusting for age, sex, and the first 5 genetic principal components, for each phenotype and each variant in the target genes (JAG1, NOTCH2 FBN1, PTPN1 and RAS-opathy genes, and genes in the 22q11.2 locus) and performed a gene burden test. Overall, we observed multiple phenotype-genotype correlations, such as the association between variation in JAG1, FBN1, PTPN11 and SOS2 with diastolic and systolic blood pressure; and pleiotropy among multiple variants in syndromic genes. For example, rs11066309 in PTPN11 was significantly associated with a lower body mass index, an increased risk of hypothyroidism and a smaller size for gestational age, all in concordance with NS-related phenotypes. Similarly, rs589668 in FBN1 was associated with an increase in body height and blood pressure, and a reduced body fat percentage as observed in Marfan syndrome. Our findings suggest that the spectrum of associations of common and rare variants in genes involved in syndromic diseases can be extended to individual phenotypes within the general population.

PMID: 33226994 [PubMed - as supplied by publisher]

Related Articles

Cardiac catheterization addressing early post-operative complications in congenital heart surgery-a single-center experience.

Egypt Heart J. 2020 Nov 23;72(1):83

Authors: Bahaidarah S, Al-Ata J, Abdelmohsen G, Alkhushi N, Abdelsalam M, Mujahed M, Al-Radi O, Elassal A, Zaher Z, Azhar A, Dohain AM

Abstract
BACKGROUND: Cardiac catheterization after congenital heart surgery may play an important role in the diagnosis and management of patients with a complicated or unusual post-operative course. The main objective of this study was to evaluate the safety, efficacy, and outcome of cardiac catheterization performed in the early post-operative period following congenital heart surgery. All patients who underwent cardiac catheterization after congenital heart surgery during the same admission of cardiac surgery from November 2015 to May 2018 were included in the study.
RESULTS: Thirty procedures were performed for 27 patients (20 interventional and 10 diagnostic). The median age of the patients was 15 months (15 days to 20 years), median weight was 8.2 kg (3.4 to 53 kg), and median time from surgery was 3 days (0-32 days). Eleven procedures were performed for 11 patients on extracorporeal membrane oxygenation (ECMO) support. The main indications for catheterization included the inability to wean from ECMO (10 procedures) and cyanosis (10 procedures). Interventional procedures included angioplasty using stents (10 procedures, success rate of 90%), angioplasty using only balloons (2 procedures, success rate of 50%), and occlusion for residual shunts (8 procedures, success rate of 100%). No mortality was recorded during any procedure. Vasoactive-inotropic score had significantly decreased 48 h after catheterization when compared to pre-catheterization scores (p = 0.0001). Moreover, 72% of patients connected to ECMO support were successfully weaned from ECMO after catheterization. Procedural complications were recorded in 3 interventional procedures. Survival to hospital discharge was 55.5% and overall survival was 52%. Patients on ECMO support had a higher mortality than other patients.
CONCLUSION: Cardiac catheterization can be performed safely in the early post-operative period, and it could improve the outcome of the patient (depending on the complexity of the cardiac lesions involved).

PMID: 33226532 [PubMed - as supplied by publisher]

Related Articles

Correction to: Multiple office blood pressure measurement: a novel approach to overcome the weak cornerstone of blood pressure measurement in children. Data from the SPA project.

Pediatr Nephrol. 2020 Nov 23;:

Authors: Ardissino G, Ghiglia S, Salice P, Perrone M, Piantanida S, De Luca FL, Di Michele S, Filippucci L, Dardi ERA, Bollani T, Mezzopane A, Tchana B, Lava SAG, SPA Project investigators

Abstract
The authors regret that the name of the author Bertrand Tchana was incorrectly rendered as "Bertrand Tchane". The original article has been corrected.

PMID: 33226476 [PubMed - as supplied by publisher]

Related Articles

Amino Acid-level Signal-to-Noise Analysis Aids in Pathogenicity Prediction of Incidentally-identified TTN-Encoded Titin Truncating Variants.

Circ Genom Precis Med. 2020 Nov 23;:

Authors: Connell PS, Berkman AM, Souder BM, Pirozzi EJ, Lovin JJ, Rosenfeld JA, Liu P, Tunuguntla H, Allen HD, Denfield SW, Kim JJ, Landstrom AP

Abstract
Background - TTN, the largest gene in the human body, encodes titin (TTN), a protein that plays key structural, developmental, and regulatory roles in skeletal and cardiac muscle. Variants in TTN, particularly truncating variants (TTNtvs), have been implicated in the pathogenicity of cardiomyopathy (CM). Despite this link, there is also a high burden of TTNtvs in the ostensibly healthy general population. This complicates the diagnostic interpretation of incidentally identified TTNtvs which are of increasing abundance given expanding clinical exome sequencing (ES). Methods - Incidentally identified TTNtvs were obtained from a large referral database of clinical ES (Baylor Genetics) and compared to rare population variants from gnomAD and CM-associated variants from cohort studies in the literature. A subset of TTNtv-positive children evaluated for cardiomyopathy at Texas Children's Hospital (TCH) were retrospectively reviewed for clinical features of cardiomyopathy. Amino acid-level signal-to-noise analysis (S:N) was performed. Results - Pathologic hotspots were identified within the A-band and N-terminal I-band that closely correlated with regions of high percent spliced in (PSI) of exons. Incidental TTNtvs and population TTNtvs did not localize to these regions. Variants were re-classified based on current ACMG criteria with incorporation of S:N analysis among TCH cases. Those re-classified as likely pathogenic or pathogenic were more likely to have evidence of CM on echocardiography than those re-classified as variants of unknown significance. Conclusions - Incidentally found TTNtvs are common among clinical ES referrals. Pathologic hotspots within the A-band of TTN may be informative in determining variant pathogenicity when incorporated into current ACMG guidelines.

PMID: 33226272 [PubMed - as supplied by publisher]

Related Articles

Molecular and histologic insights on early onset cardiomyopathy in Danon disease females.

Clin Genet. 2020 Nov 23;:

Authors: Fernández L, Casamayor Polo L, Bravo García-Morato M, Enguita Valls AB, Ruiz-Bravo E, Muñoz-Cabello P, Ibáñez K, Rodríguez-Laguna L, Martín-Arenas R, Ortega M, Palomares-Bralo M, Del Pozo Á, García-Guereta L, García-Miñaúr S, Lapunzina P, Vallespín E

PMID: 33226119 [PubMed - as supplied by publisher]

Related Articles

Management of aortic arch hypoplasia in neonates and infants.

J Card Surg. 2020 Nov 22;:

Authors: Onalan MA, Temur B, Aydın S, Basgoze S, Guzelmeric F, Odemis E, Erek E

Abstract
OBJECTIVES: Surgical management of aortic arch hypoplasia (AAH) with associated intracardiac anomalies is a challenge in newborns. We reviewed the characteristics and outcomes of neonates and infants who underwent pulmonary artery banding concomitant to arch repair and single-stage total repair at our institution.
METHODS: Medical records of 60 patients undergoing aortic arch reconstruction for AAH from 2014 to 2019 were retrospectively reviewed. Twenty-five patients were female (41.6%), and the age of the patients ranged from 4 to 120 days (median, 19.5 days). The patients were divided into two groups: Group 1 (23 patients) underwent pulmonary artery banding concomitant to arch repair, and Group 2 (37 patients) underwent single-stage total repair in addition to arch repair. All arch repair procedures consisted of an extended (to the midportion of the ascending aorta) patch aortoplasty.
RESULTS: Postoperative early mortality occurred in 12 patients, eight in Group 1 (34.8%) and four in Group 2 (10.8%). There was an early survival advantage in Group 2 (p = .019). Recoarctation occurred in 13 cases (21.6%), and 11 (18.3%) of them required reintervention (balloon angioplasty: 7, reoperation: 4). On univariate analysis, risk factors associated with death were pulmonary artery banding (hazard ratio [HR], 0.44; confidence interval [CI], 0.09-2; p = .019), prematurity (HR, 4.67; CI, 1.34-16.18; p = <.001), preoperative mechanical ventilation support requirement (HR, 0.048; CI, 0.52-6.39; p = .048), and functional single ventricle (HR, 0.43; CI, 0.1-1.86; p = .006). The mean duration of follow-up was 21.9 ± 15.1 months, and there was no late death in either group.
CONCLUSION: Single-stage repair of AAH with intracardiac pathologies has better results than palliation, according to survival rates and postoperative results. The use of the patch augmentation technique in AAH is valid and associated with an acceptable incidence of recurrent arch obstruction.

PMID: 33225505 [PubMed - as supplied by publisher]

Related Articles

Assessment of Ethanol-Induced Toxicity on iPSC-Derived Human Neurons Using a Novel High-Throughput Mitochondrial Neuronal Health (MNH) Assay.

Front Cell Dev Biol. 2020;8:590540

Authors: Zink A, Conrad J, Telugu NS, Diecke S, Heinz A, Wanker E, Priller J, Prigione A

Abstract
Excessive ethanol exposure can cause mitochondrial and cellular toxicity. In order to discover potential counteracting interventions, it is essential to develop assays capable of capturing the consequences of ethanol exposure in human neurons, and particularly dopaminergic neurons that are crucial for the development of alcohol use disorders (AUD). Here, we developed a novel high-throughput (HT) assay to quantify mitochondrial and neuronal toxicity in human dopaminergic neuron-containing cultures (DNs) from induced pluripotent stem cells (iPSCs). The assay, dubbed mitochondrial neuronal health (MNH) assay, combines live-cell measurement of mitochondrial membrane potential (MMP) with quantification of neuronal branching complexity post-fixation. Using the MNH assay, we demonstrated that chronic ethanol exposure in human iPSC-derived DNs decreases MMP and neuronal outgrowth in a dose-dependent manner. The toxic effect of ethanol on DNs was already detectable after 1 h of exposure, and occurred similarly in DNs derived from healthy individuals and from patients with AUD. We next used the MNH assay to carry out a proof-of-concept compound screening using FDA-approved drugs. We identified potential candidate compounds modulating acute ethanol toxicity in human DNs. We found that disulfiram and baclofen, which are used for AUD treatment, and lithium caused neurotoxicity also in the absence of ethanol, while the spasmolytic drug flavoxate positively influenced MNH. Altogether, we developed an HT assay to probe human MNH and used it to assess ethanol neurotoxicity and to identify modulating agents. The MNH assay represents an effective new tool for discovering modulators of MNH and toxicity in live human neurons.

PMID: 33224955 [PubMed]

Related Articles

Emerging therapies for right ventricular dysfunction and failure.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1735-1767

Authors: Klinke A, Schubert T, Müller M, Legchenko E, Zelt JGE, Shimauchi T, Napp LC, Rothman AMK, Bonnet S, Stewart DJ, Hansmann G, Rudolph V

Abstract
Therapeutic options for right ventricular (RV) dysfunction and failure are strongly limited. Right heart failure (RHF) has been mostly addressed in the context of pulmonary arterial hypertension (PAH), where it is not possible to discern pulmonary vascular- and RV-directed effects of therapeutic approaches. In part, opposing pathomechanisms in RV and pulmonary vasculature, i.e., regarding apoptosis, angiogenesis and proliferation, complicate addressing RHF in PAH. Therapy effective for left heart failure is not applicable to RHF, e.g., inhibition of adrenoceptor signaling and of the renin-angiotensin system had no or only limited success. A number of experimental studies employing animal models for PAH or RV dysfunction or failure have identified beneficial effects of novel pharmacological agents, with most promising results obtained with modulators of metabolism and reactive oxygen species or inflammation, respectively. In addition, established PAH agents, in particular phosphodiesterase-5 inhibitors and soluble guanylate cyclase stimulators, may directly address RV integrity. Promising results are furthermore derived with microRNA (miRNA) and long non-coding RNA (lncRNA) blocking or mimetic strategies, which can target microvascular rarefaction, inflammation, metabolism or fibrotic and hypertrophic remodeling in the dysfunctional RV. Likewise, pre-clinical data demonstrate that cell-based therapies using stem or progenitor cells have beneficial effects on the RV, mainly by improving the microvascular system, however clinical success will largely depend on delivery routes. A particular option for PAH is targeted denervation of the pulmonary vasculature, given the sympathetic overdrive in PAH patients. Finally, acute and durable mechanical circulatory support are available for the right heart, which however has been tested mostly in RHF with concomitant left heart disease. Here, we aim to review current pharmacological, RNA- and cell-based therapeutic options and their potential to directly target the RV and to review available data for pulmonary artery denervation and mechanical circulatory support.

PMID: 33224787 [PubMed]

Related Articles

Cardiac catheterization in pulmonary hypertension: doing it right, with a catheter on the left.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1718-1724

Authors: Hansmann G, Rich S, Maron BA

PMID: 33224785 [PubMed]

Related Articles

Interventional creation of an endogenous reverse Potts shunt in an infant with pulmonary hypertension and genetic surfactant disorder-a case report.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1696-1700

Authors: Sallmon H, Berger F, Weber SC, Fischer HS, Hansmann G, Opgen-Rhein B

Abstract
Reverse Potts shunt is a palliative procedure aimed at decompressing the pressure-overloaded right ventricle in severe pulmonary hypertension (PH). We, herein, report the first case of an interventional creation of an "endogenous" reverse Potts shunt by stenting a pre-existing small but patent ductus arteriosus (PDA) in a 2 months old female infant with severe, supra-systemic PH, associated with a novel combination of a compound heterozygous ABCA3 mutation and additional heterozygous genetic variants of surfactant protein B (SFTPB) and C (SFTPC). The aforementioned combination of human genetic mutations has not been described before in viable infants, children or adults. The catheter intervention was performed via percutaneous femoral arterial access and was well-tolerated. Subsequently, the infant improved by means of clinical status, echocardiographic systolic right ventricular (RV) function, and serum NT-proBNP levels as biomarker of right atrial and RV pressure load. In conclusion, this single case report suggests that interventional stenting of a pre-existing PDA to create an "endogenous" reverse Potts shunt is feasible and efficacious in infants less than 3 months old with severe PH and impending RV failure associated with developmental lung disease.

PMID: 33224783 [PubMed]

Related Articles

Mineralocorticoid receptor blockade improves pulmonary hypertension and right ventricular function in bronchopulmonary dysplasia: a case report.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1686-1690

Authors: Giagnorio R, Hansmann G

Abstract
Bronchopulmonary dysplasia (BPD) is a combined pulmonary vascular and parenchymal disease, representing the most common cause of chronic lung disease (CLD) in infancy. Pulmonary hypertension (PH) is frequently associated with BPD and-if persistent-substantially increases mortality. We report on a 4-month-old, former preterm infant with BPD, severe PH and right heart failure who greatly and rapidly improved clinical status and right ventricular (RV) function by means of blood biomarkers [N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP), cardiac troponin T] and transthoracic echocardiography, following the addition of spironolactone and hydrochlorothiazide to the treatment regimen.

PMID: 33224781 [PubMed]

Related Articles

Safety and efficacy of the endothelin receptor antagonist macitentan in pediatric pulmonary hypertension.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1675-1685

Authors: Schweintzger S, Koestenberger M, Schlagenhauf A, Grangl G, Burmas A, Kurath-Koller S, Pocivalnik M, Sallmon H, Baumgartner D, Hansmann G, Gamillscheg A

Abstract
Background: Macitentan, a dual endothelin receptor antagonist (ERA), was approved in 2014 for the treatment of adults with idiopathic pulmonary arterial hypertension (PAH). Once-per-day dosing and low potential hepatic toxicity make macitentan an appealing therapeutic option for children with PAH, but reports on its use in pediatric patients are still lacking.
Methods: Prospective observational study of 18 children [10 male; median age: 8.5, minimum (min.): 0.6, maximum (max.): 16.8 years] with pulmonary hypertension (PH). Four of these 18 patients were treatment-naïve and started on a de novo macitentan therapy. The remaining 14/18 children were already on a PH-targeted pharmacotherapy (sildenafil or bosentan as monotherapy or in combination). Nine children who were on bosentan were switched to macitentan. We analyzed the 6-minute walking distance (6MWD), NYHA functional class (FC)/modified ROSS score, invasive hemodynamics, echocardiographic variables and the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP).
Results: The median follow up was 6 months (min.: 0.5, max.: 30). Macitentan treatment was associated with improvement of invasive hemodynamics, e.g., the ratio of mean pulmonary arterial pressure/mean systemic arterial pressure decreased from a median of 62% (min.: 30%, max.: 87%) to 49% (min.: 30%, max.: 69%), P<0.05; pulmonary vascular resistance index (PVRi) decreased from a median of 7.6 (min.: 3.3, max.: 11.5) to 4.8 Wood units × m2 body surface area (min.: 2.5, max.: 10), P<0.05. The tricuspid annular plane systolic excursion (TAPSE) increased from a median of 1.4 (min.: 0.8, max.: 2.8) to 1.9 (min.: 0.8, max.: 2.7) cm, (P<0.05). NT-proBNP values decreased from a median of 272 (min.: 27, max.: 2,010) to 229 (min.: 23, max.: 814) pg/mL under macitentan therapy (P<0.05). The 6MWD and NYHA FC/modified ROSS score did not change significantly.
Conclusions: This is the first prospective study of macitentan pharmacotherapy in infants and children with PH <12 years of age. Except in one patient, macitentan treatment was well tolerated and was associated with improvements in invasive hemodynamics, longitudinal systolic RV function (TAPSE) and serum NT-proBNP values.

PMID: 33224780 [PubMed]

Related Articles

Treatment of right ventricular dysfunction and heart failure in pulmonary arterial hypertension.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1659-1674

Authors: Inampudi C, Tedford RJ, Hemnes AR, Hansmann G, Bogaard HJ, Koestenberger M, Lang IM, Brittain EL

Abstract
Right heart dysfunction and failure is the principal determinant of adverse outcomes in patients with pulmonary arterial hypertension (PAH). In addition to right ventricular (RV) dysfunction, systemic congestion, increased afterload and impaired myocardial contractility play an important role in the pathophysiology of RV failure. The behavior of the RV in response to the hemodynamic overload is primarily modulated by the ventricular interaction and its coupling to the pulmonary circulation. The presentation can be acute with hemodynamic instability and shock or chronic producing symptoms of systemic venous congestion and low cardiac output. The prognostic factors associated with poor outcomes in hospitalized patients include systemic hypotension, hyponatremia, severe tricuspid insufficiency, inotropic support use and the presence of pericardial effusion. Effective therapeutic management strategies involve identification and effective treatment of the triggering factors, improving cardiopulmonary hemodynamics by optimization of volume to improve diastolic ventricular interactions, improving contractility by use of inotropes, and reducing afterload by use of drugs targeting pulmonary circulation. The medical therapies approved for PAH act primarily on the pulmonary vasculature with secondary effects on the right ventricle. Mechanical circulatory support as a bridge to transplantation has also gained traction in medically refractory cases. The current review was undertaken to summarize recent insights into the evaluation and treatment of RV dysfunction and failure attributable to PAH.

PMID: 33224779 [PubMed]

Related Articles

Right ventricular dysfunction and long-term risk of death.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1646-1658

Authors: Sanders JL, Koestenberger M, Rosenkranz S, Maron BA

Abstract
Sudden cardiac death (SCD), or sudden loss of life-sustaining systemic and cerebral perfusion, is most often due to left ventricular (LV) dysfunction secondary to ischemic or structural cardiac disease or channelopathies. Degeneration of sinus rhythm into ventricular tachycardia and ultimately ventricular fibrillation is the final common pathway for most heart failure patients. Right ventricular (RV) dysfunction is recognized as an independent contributor to worsening heart failure. There is emerging evidence that RV dysfunction may also be an independent predictor of SCD. This review examines the role of RV dysfunction on modifying long term risk of SCD, and explores possible mechanisms that may underlie SCD. The RV has unique anatomy and physiology compared to the LV. Subsequently, we begin with a review of cardiac embryology, focusing on the chambers, valves, coronary arteries, and cardiac conduction system to understand the origins of RV dysfunction. Static and dynamic physiology of the RV is contrasted with that of the LV. Particular emphasis is placed on ventriculo-arterial coupling, mechanical cardiac constraint, and ventricular interdependence. The epidemiology of SCD is briefly reviewed to highlight how causes of SCD are age-specific. In turn, the age-specific causes of RV dysfunction are presented, including those which predominate in childhood and adolescence [arrhythmogenic RV dysplasia (ARVD) and hypertrophic cardiomyopathy (HCM)] and older adulthood (cardiac ischemia, chronic congestive heart failure and post-capillary pulmonary hypertension, and pulmonary hypertension). There is a clear need for additional studies on the independent contribution of RV dysfunction to overall functional capacity, SCD-associated mortality, and non-SCD-associated mortality. Discovery would be aided by the development of prospective cohorts with excellent RV phenotyping, coupled with deeper biologic measurements linking mechanisms to clinically relevant outcomes.

PMID: 33224778 [PubMed]

Related Articles

Diagnosis and treatment of right ventricular dysfunction in congenital heart disease.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1625-1645

Authors: Santens B, Van De Bruaene A, De Meester P, D'Alto M, Reddy S, Bernstein D, Koestenberger M, Hansmann G, Budts W

Abstract
Right ventricular (RV) function is important for clinical status and outcomes in children and adults with congenital heart disease (CHD). In the normal RV, longitudinal systolic function is the major contributor to global RV systolic function. A variety of factors contribute to RV failure including increased pressure- or volume-loading, electromechanical dyssynchrony, increased myocardial fibrosis, abnormal coronary perfusion, restricted filling capacity and adverse interactions between left ventricle (LV) and RV. We discuss the different imaging techniques both at rest and during exercise to define and detect RV failure. We identify the most important biomarkers for risk stratification in RV dysfunction, including abnormal NYHA class, decreased exercise capacity, low blood pressure, and increased levels of NTproBNP, troponin T, galectin-3 and growth differentiation factor 15. In adults with CHD (ACHD), fragmented QRS is independently associated with heart failure (HF) symptoms and impaired ventricular function. Furthermore, we discuss the different HF therapies in CHD but given the broad clinical spectrum of CHD, it is important to treat RV failure in a disease-specific manner and based on the specific alterations in hemodynamics. Here, we discuss how to detect and treat RV dysfunction in CHD in order to prevent or postpone RV failure.

PMID: 33224777 [PubMed]

Related Articles

Update on noninvasive imaging of right ventricle dysfunction in pulmonary hypertension.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1604-1624

Authors: Truong U, Meinel K, Haddad F, Koestenberger M, Carlsen J, Ivy D, Jone PN

Abstract
Pulmonary hypertension (PH) is a progressive disease affecting patients across the life span. The pathophysiology primarily involves the pulmonary vasculature and right ventricle (RV), but eventually affects the left ventricular (LV) function as well. Safe, accurate imaging modalities are critical for diagnosis, serial monitoring, and tailored therapy. While cardiac catheterization remains the conventional modality for establishing diagnosis and serial monitoring, noninvasive imaging has gained considerable momentum in providing accurate assessment of the entire RV-pulmonary axis. In this state-of-the-art review, we will discuss the most recent developments in echocardiography, magnetic resonance imaging, and computed tomography in PH evaluation from pediatric to adult population.

PMID: 33224776 [PubMed]

Related Articles

Mechanics of right ventricular dysfunction in pulmonary arterial hypertension and heart failure with preserved ejection fraction.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1580-1603

Authors: Bernardo RJ, Haddad F, Couture EJ, Hansmann G, de Jesus Perez VA, Denault AY, de Man FS, Amsallem M

Abstract
Right ventricular (RV) dysfunction is the most important determinant of survival in patients with pulmonary hypertension (PH). The manifestations of RV dysfunction not only include changes in global RV systolic function but also abnormalities in the pattern of contraction and synchrony. The effects of PH on the right ventricle have been mainly studied in patients with pulmonary arterial hypertension (PAH). However, with the demographic shift towards an aging population, heart failure with preserved ejection fraction (HFpEF) has become an important etiology of PH in recent years. There are significant differences in RV mechanics, function and adaptation between patients with PAH and HFpEF (with or without PH), which are related to different patterns of remodeling and dysfunction. Due to the unique features of the RV chamber, its connection with the main pulmonary artery and the pulmonary circulation, an understanding of the mechanics of RV function and its clinical significance is mandatory for both entities. In this review, we describe the mechanics of the pressure overloaded right ventricle. We review the different mechanical components of RV dysfunction and ventricular dyssynchrony, followed by insights via analysis of pressure-volume loop, energetics and novel blood flow patterns, such as vortex imaging. We conduct an in-depth comparison of prevalence and characteristics of RV dysfunction in HFpEF and PAH, and summarize key outcome studies. Finally, we provide a perspective on needed and expected future work in the field of RV mechanics.

PMID: 33224775 [PubMed]

Related Articles

Animal models of right heart failure.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1561-1579

Authors: Andersen A, van der Feen DE, Andersen S, Schultz JG, Hansmann G, Bogaard HJ

Abstract
Right heart failure may be the ultimate cause of death in patients with acute or chronic pulmonary hypertension (PH). As PH is often secondary to other cardiovascular diseases, the treatment goal is to target the underlying disease. We do however know, that right heart failure is an independent risk factor, and therefore, treatments that improve right heart function may improve morbidity and mortality in patients with PH. There are no therapies that directly target and support the failing right heart and translation from therapies that improve left heart failure have been unsuccessful, with the exception of mineralocorticoid receptor antagonists. To understand the underlying pathophysiology of right heart failure and to aid in the development of new treatments we need solid animal models that mimic the pathophysiology of human disease. There are several available animal models of acute and chronic PH. They range from flow induced to pressure overload induced right heart failure and have been introduced in both small and large animals. When initiating new pre-clinical or basic research studies it is key to choose the right animal model to ensure successful translation to the clinical setting. Selecting the right animal model for the right study is hence important, but may be difficult due to the plethora of different models and local availability. In this review we provide an overview of the available animal models of acute and chronic right heart failure and discuss the strengths and limitations of the different models.

PMID: 33224774 [PubMed]

Related Articles

Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1522-1540

Authors: Agrawal V, Lahm T, Hansmann G, Hemnes AR

Abstract
Pulmonary arterial hypertension (PAH) is a rare, life-threatening condition characterized by dysregulated metabolism, pulmonary vascular remodeling, and loss of pulmonary vascular cross-sectional area due to a variety of etiologies. Right ventricular (RV) dysfunction in PAH is a critical mediator of both long-term morbidity and mortality. While combinatory oral pharmacotherapy and/or intravenous prostacyclin aimed at decreasing pulmonary vascular resistance (PVR) have improved clinical outcomes, there are currently no treatments that directly address RV failure in PAH. This is, in part, due to the incomplete understanding of the pathogenesis of RV dysfunction in PAH. The purpose of this review is to discuss the current understanding of key molecular mechanisms that cause, contribute and/or sustain RV dysfunction, with a special focus on pathways that either have led to or have the potential to lead to clinical therapeutic intervention. Specifically, this review discusses the mechanisms by which vessel loss and dysfunctional angiogenesis, sex hormones, and metabolic derangements in PAH directly contribute to RV dysfunction. Finally, this review discusses limitations and future areas of investigation that may lead to novel understanding and therapeutic interventions for RV dysfunction in PAH.

PMID: 33224772 [PubMed]

Related Articles

Getting to the bottom of right heart failure.

Cardiovasc Diagn Ther. 2020 Oct;10(5):1517-1521

Authors: Koestenberger M, Bogaard HJ, Hansmann G

PMID: 33224771 [PubMed]

Related Articles

Promising preventive and therapeutic effects of TaibUVID nutritional supplements for COVID-19 pandemic: towards better public prophylaxis and treatment (A retrospective study).

Am J Blood Res. 2020;10(5):266-282

Authors: El Sayed SM, Aboonq MS, El Rashedy AG, Aljehani YT, Abou El-Magd RM, Okashah AM, El-Anzi ME, Alharbi MB, El-Tahlawi R, Nabo MMH, Yousef RS, Elshazley M, Abu-Elnaga M, Mahmoud HS, El-Alaf H, Abdelrahman AI, Abdel-Gawad AR, Soliman TM

Abstract
Adjuvant nutritional treatment is a commonly overlooked topic when treating lethal viral diseases as COVID-19 pandemic. We recently introduced TaibUVID nutritional supplements (nigella sativa, chamomile and natural honey) as adjuvants for COVID-19 contacts, patients and public prophylaxis. TaibUVID Forte adds costus, senna and fennel to TaibUVID. Meta-analyses and systematic reviews confirmed evidence-based therapeutic benefits of TaibUVID components in treating many human diseases e.g. diabetes mellitus and hypertension, common co-morbidities in COVID-19 patients. Double-blind clinical trials for treating COVID-19 patients with TaibUVID supplements were inapplicable. In this retrospective study in Egypt, COVID-19 patients and contacts knew TaibUVID via social media and voluntarily used them. 65% of COVID-19 patients (n = 13) received both pharmacological treatments and adjuvant TaibUVID nutritional supplements. 35% (n = 7) received TaibUVID only. Lymphopenia rapidly improved to lymphocytosis upon regular TaibUVID intake. TaibUVID nutritional supplements helped COVID-19 contacts' prophylaxis. 70% of COVID-19 contacts (n = 14) (on regular TaibUVID intake) did not get SARS-COV2 infection. 30% (n = 6) were not using TaibUVID regularly and got mild flu-like symptoms and upon using both TaibUVID and pharmacological treatments, all improved and got negative nasopharyngeal swabs PCR. COVID-19 contacts were mainly physicians (40%, n = 8) (dealing with COVID-19 patients daily) and members of physicians' families (45%). Main presentations reported by COVID-19 patients (n = 20) were cough (90%), fever (55%), anosmia (45%), taste loss (45%), sore throat (45%), respiratory difficulty (45%) and malaise (35%). TaibUVID inhalation therapy (nigella sativa/anthemis/costus solution nebulization) was used by 65% of COVID-19 patients (n = 13) and alleviated respiratory manifestations e.g. cough and respiratory difficulty and was life-saving in some cases. 70% of COVID-19 patients (n = 14) improved in 1-4 days, 25% (n = 5) improved in 5-10 days while 5% improved in more than 10 days. TaibUVID nutritional supplements were tolerable and significantly satisfactory (P<0.01). 81.25% of COVID-19 patients (n = 13) did not report side effects. 18.25% (n = 3) reported mild diarrhea, sweating and hyperglycemia (not confirmed to be due to TaibUVID supplements). 31.25% of patients (n = 5) were satisfied by 100% with TaibUVID nutritional supplements. 37.5% (n = 6) of patients were satisfied by 75%. In conclusion, TaibUVID nutritional supplements are recommended for public prophylaxis (to decrease emergence of new cases) and treatment in COVID-19 pandemic. Clinical trials and further investigations are recommended.

PMID: 33224571 [PubMed]

Related Articles

A Rare Cause of Pulmonary Hypertension in a 4-Year-Old Toddler: Association of Cor Triatriatum Sinister and Pulmonary Arteriovenous Malformation.

Case Rep Pediatr. 2020;2020:8825215

Authors: Yozgat CY, Cakir E, Yazan H, Temur HO, Yakut K, Yozgat Y

Abstract
Cor triatriatum sinister is a rare congenital cardiac anomaly. The anomaly is caused by a fibromuscular membrane that divides the left atrium into two cavities. This membrane can lead to the obstruction of left atrial flow and also create pulmonary venous hypertension. Pulmonary arteriovenous malformation (PAVM) is notorious for its aberrant blood flow between the pulmonary arteries and veins. Herein, we report a case of a 4-year-old toddler who had a unique form of pulmonary hypertension presenting with cor triatriatum sinister and diffuse PAVM. After the surgical treatment of cor triatriatum sinister, both pulmonary arteriovenous malformation and pulmonary hypertension disappeared.

PMID: 33224546 [PubMed]

Related Articles

Cognitive and Attentional Function in Children with Hypoplastic Left Heart Syndrome: A Pilot Study.

J Clin Psychol Med Settings. 2020 Nov 22;:

Authors: Siciliano RE, Murphy LK, Prussien KV, Henry LM, Watson KH, Patel NJ, Lee CA, McNally CM, Markham LW, Compas BE, Jordan LC

Abstract
While survival for children with hypoplastic left heart syndrome (HLHS) has improved, compromised cardiac output and oxygen delivery persist, and children show cognitive deficits. Most research has assessed young children on broad cognitive indices; less is known about specific indices in older youth. In this pilot study, cognitive function and attention in youth ages 8 to 16 years with HLHS (n = 20) was assessed with the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) and NIH Toolbox Cognition Battery (NTCB); parents completed the Child Behavior Checklist. Children scored significantly lower than normative means on the WISC-V Full Scale IQ, Verbal Comprehension, Visual Spatial, Working Memory, and Processing Speed indices, and the NTCB Fluid Cognition Composite; effect sizes ranged from medium to large. Attention problems had a large significant effect. Child age corresponded to lower visual spatial scores. Findings highlight the importance of assessing multiple cognitive indices for targeted intervention and investigating age and disease factors as potential correlates in larger samples.

PMID: 33222094 [PubMed - as supplied by publisher]

Icon for Silverchair Information Systems Related Articles

Hypothermia for cardiogenic encephalopathy in neonates with dextro-transposition of the great arteries.

Interact Cardiovasc Thorac Surg. 2020 Nov 22;:

Authors: Boos V, Bührer C, Photiadis J, Berger F

Abstract
OBJECTIVES: Neonates with dextro-transposition of the great arteries (d-TGA) may experience rapid haemodynamic deterioration and profound hypoxaemia after birth. We report on d-TGA patients with severe acidosis, encephalopathy and their treatment with systemic hypothermia.
METHODS: This study is a single-centre retrospective cohort analysis of newborns with d-TGA.
RESULTS: Ninety-five patients (gestational age ≥35 weeks) with d-TGA and intended arterial switch operation were included. Ten infants (10.5%) with umbilical arterial blood pH > 7.10 experienced profound acidosis (pH < 7.00) within the first 2 h of life. Six of these patients displayed signs of encephalopathy and received therapeutic hypothermia. Apgar scores at 5 min independently predicted the development of neonatal encephalopathy during postnatal transition (unit Odds Ratio 0.17, 95% confidence interval 0.06-0.49, P = 0.001). Infants treated with hypothermia had a more severe preoperative course and required more often mechanical ventilation (100% vs 35%, P = 0.003), treatment with inhaled nitric oxide (50% vs 2.4%, P = 0.002) and inotropic support (67% vs 3.5%, P < 0.001), as compared to non-acidotic controls. The median age at cardiac surgery was 12 (range 6-14) days in cooled infants and 8 (4-59) days in controls (P = 0.088). Postoperative morbidity and total duration of hospitalization were not increased in infants receiving preoperative hypothermia. Mortality in newborns with severe preoperative acidosis was zero.
CONCLUSIONS: Newborn infants with d-TGA have a substantial risk for profound acidosis during the first hours of life. Systemic hypothermia for encephalopathic patients may delay corrective surgery without compromising perioperative outcomes.

PMID: 33221903 [PubMed - as supplied by publisher]

Icon for Silverchair Information Systems Related Articles

Three-step preoperative sequential planning for pulmonary valve replacement in repaired tetralogy of Fallot using computed tomography.

Eur J Cardiothorac Surg. 2020 Nov 22;:

Authors: Ferraz Cavalcanti PE, Sá MPBO, Lins RFA, Cavalcanti CV, Lima RC, Cvitkovic T, Bobylev D, Boethig D, Beerbaum P, Sarikouch S, Haverich A, Horke A

Abstract
OBJECTIVES: Our goal was to compare results between a standard computed tomography (CT)-based strategy, the 'three-step preoperative sequential planning' (3-step PSP), for pulmonary valve replacement in repaired tetralogy of Fallot versus a conventional planning approach.
METHODS: We carried out a retrospective study with unmatched and matched groups. The 3-step PSP comprised the planning of mediastinal re-entry, cannulation for cardiopulmonary bypass (CPB) and the main procedure, using standard 3-dimensional videos. Operative times (skin incision to CPB, CPB time, end of CPB to skin closure and cross-clamp time) as well as postoperative length of stay and in-hospital mortality were compared.
RESULTS: Eighty-two patients (49% classical tetralogy of Fallot) underwent an operation (85% with pulmonary homograft) with 1.22% in-hospital mortality. The 3-step PSP (n = 14) and the conventional planning (n = 68) groups were compared. There were no statistically significant differences in the preoperative characteristics. Differences were observed in the total operative time (P = 0.009), skin incision to CPB (P = 0.034) and cross-clamp times (74 ± 33 vs 108 ± 47 min; P = 0.006), favouring the 3-step PSP group. Eight matched pairs were compared showing differences in the total operative time (263 ± 44 vs 360 ± 66 min; P = 0.008), CPB time (123 ± 34 vs 190 ± 43 min; P = 0.008) and postoperative length of stay (P = 0.031), favouring the 3-step PSP group.
CONCLUSIONS: In patients with repaired tetralogy of Fallot undergoing pulmonary valve replacement, preoperative planning using a standard CT-based strategy, the 3-step PSP, is associated with shorter operative times and shorter postoperative length of stay.

PMID: 33221863 [PubMed - as supplied by publisher]

Icon for Silverchair Information Systems Related Articles

Congenital atresia of the left main coronary artery: management of a 5-year-old child in extremis.

Interact Cardiovasc Thorac Surg. 2020 Nov 22;:

Authors: Schmiady M, Kretschmar O, Prêtre R, Dave H

Abstract
Atresia of the left main coronary artery is a rare coronary anomaly. We describe the case of a 5-year-old child presenting in emergency in extremis. Clinical findings of haemodynamic collapse, malignant ventricular tachyarrhythmias and severe mitral regurgitation were indicative of a possible ischaemic aetiology. Surgical revascularization of the atretic left main coronary artery segment using an interposition autologous saphenous vein graft was successfully performed.

PMID: 33221860 [PubMed - as supplied by publisher]

Icon for Silverchair Information Systems Related Articles

Aortic valve neocuspidalization in paediatric patients with isolated aortic valve disease: early experience.

Interact Cardiovasc Thorac Surg. 2020 Nov 21;:

Authors: Polito A, Albanese SB, Cetrano E, Cicenia M, Rinelli G, Carotti A

Abstract
OBJECTIVES: There is growing interest in the aortic valve (AV) neocuspidalization technique for the treatment of aortic valve disease (AVD). We report our medium-term results with this procedure performed in a paediatric patient population.
METHODS: Between July 2016 and May 2020, 22 patients with both congenital and acquired isolated AVD were treated with neocuspidalization. The primary outcome was progression of the preoperatively assessed AVD in the immediate postoperative course and at follow-up. Secondary outcome was freedom from reintervention by material used. Potential predictors of failure were analysed in relation to the primary outcome.
RESULTS: The median age at operation was 13.9 (interquartile range, 9.8-16.2) years, and the prevailing AV defect was stenosis in 10 cases (45%) and incompetence in 12 (55%). Pre-treated autologous pericardium was used in 13 patients whereas bovine pericardium in 9. Effective treatment of AV stenosis or regurgitation was achieved and remained stable over a median follow-up of 11.3 (4.7-21) months. Three patients required AV replacement at 4.9, 3.5 and 33 months. At follow-up, an upward trend of both median indexed vena contracta jet widths and aortic peak and mean gradients were recorded, the latter associated with a failure to grow the aortic annulus. Predictor of such outcome turned out to be the use of bovine pericardium. A significant inverse linear correlation between AV peak gradient at follow-up and preoperative aortic annular size (P = 0.008) was also demonstrated.
CONCLUSIONS: The Ozaki procedure is safe and effective in paediatric patients with AV disease. The use of heterologous pericardium should probably be minimized. Moreover, preoperative small aortic annuli should probably be promptly treated by means of an associated ring enlargement procedure.

PMID: 33221849 [PubMed - as supplied by publisher]

Icon for Elsevier Science Related Articles

Progression in Fontan conduit stenosis and hemodynamic impact during childhood and adolescence.

J Thorac Cardiovasc Surg. 2020 Oct 29;:

Authors: Patel ND, Friedman C, Herrington C, Wood JC, Cheng AL

Abstract
OBJECTIVE: To characterize changes in Fontan conduit size over time and determine if cross-sectional area (CSA) affects cardiac output, pulmonary artery growth, and exercise capacity.
METHODS: We conducted a retrospective cross-sectional study of patients with Fontan physiology who underwent cardiac magnetic resonance imaging or cardiac catheterization between January 2013 and October 2019. We collected Fontan and pulmonary artery measurements, hemodynamic data, and cardiopulmonary exercise test data. We identified 158 patients with an extracardiac Fontan. We measured minimum and mean Fontan conduit CSA and assessed whether these correlated with Nakata index, cardiac index, or exercise capacity.
RESULTS: Minimum Fontan CSA decreased by a median of 33% (24%, 40%) during a mean follow-up of 9.6 years. Median percentage decrease in Fontan CSA did not differ among 16-, 18-, and 20-mm conduits (P = .29). There was a significant decrease in the minimum Fontan CSA (33% [25%, 41%]) starting less than 1-year post-Fontan. Median Nakata index was 177.6 mm2/m2 (149.1, 210.8) and was not associated with Fontan CSA/BSA (ρ = 0.09, P = .29). Fontan CSA/BSA was not associated with cardiac index (ρ = -0.003, P = .97). A larger Fontan CSA/BSA had a modest correlation with % predicted oxygen consumption (ρ = 0.31, P = .013).
CONCLUSIONS: Fontan conduit CSA decreases as early as 6 months post-Fontan. The minimum Fontan CSA/BSA was not associated with cardiac index or pulmonary artery size but did correlate with % predicted peak oxygen consumption.

PMID: 33220959 [PubMed - as supplied by publisher]

Icon for Elsevier Science Related Articles

Anatomical Concordance of Neonatologist Performed Echocardiography as part of Hemodynamic Consultation and Pediatric Cardiology.

J Am Soc Echocardiogr. 2020 Nov 18;:

Authors: Bischoff AR, Giesinger RE, Rios DR, Mertens L, Ashwath R, McNamara PJ

Abstract
BACKGROUND: Targeted neonatal echocardiography (TnECHO) performed by neonatologists as part of a hemodynamics consultation is increasingly being utilized in neonatal intensive care units. To minimize delays in obtaining physiological data, first echocardiograms may be performed by the neonatal hemodynamics team and reviewed afterwards by a pediatric cardiologist. This practice has not been systematically evaluated.
OBJECTIVE: To compare concordance between the anatomic findings reported by TnECHO and pediatric cardiology reports.
METHODS: This is a retrospective evaluation of 339 infants at low risk for congenital heart disease (CHD) admitted to two large referral centers with established neonatal hemodynamics programs who underwent comprehensive TnECHO as their first postnatal echocardiogram. The protocol included comprehensive imaging of intracardiac anatomy, outflow tract concordance and integrity, aortic arch anatomy, pulmonary vein location/flow, and transitional shunts. The hemodynamic consultation note was compared to the cardiology reports to determine anatomical concordance or major/minor discrepancies in all first studies.
RESULTS: Anatomical concordance occurred in 97.9% [К 0.862 (95% CI 0.762-0.962), p<0.001]. There were 7 minor discrepancies (small muscular ventricular septal defects and coronary fistulas). The index population included 23 infants (6.7%) CHD, of whom only one (0.3%) had a ductal-dependent lesion (coarctation of the aorta) which was correctly identified by both teams.
CONCLUSION: The rate of major CHD in patients considered eligible for hemodynamic consultation was low and there was high diagnostic concordance between trained neonatal hemodynamics specialists and pediatric cardiology. First echocardiograms performed by subspecialty neonatologists may provide imaging of sufficient quality to evaluate a critically unwell neonate with low suspicion for critical CHD lesions. These results should not be extrapolated to infants where CHD is suspected. This study highlights the importance of formalized, rigorous and standardized training for neonatologists with hemodynamic expertise who perform timely TnECHO assessments.

PMID: 33220434 [PubMed - as supplied by publisher]

Icon for Elsevier Science Related Articles

Trans-catheter atrial septal defect closure with the new GORE® cardioform ASD occluder: First European experience.

Int J Cardiol. 2020 Nov 18;:

Authors: Santoro G, Castaldi B, Cuman M, Candia AD, Pizzuto A, Sirico D, Cantinotti M, Garibaldi S, Pak V, Di Salvo G

Abstract
BACKGROUND: This perspective, observational study evaluated safety and efficacy of the GORE® Cardioform ASD Occluder (WL Gore & Associates, Flagstaff, AZ), compliant and potentially innovative prosthesis recently approved for closure of ostium secundum atrial septal defects (ASD).
METHODS: Between January and June 2020, 43 unselected patients with -significant ASD were submitted to trans-catheter closure with GORE® Cardioform ASD Occluder at two high-volume Italian Pediatric Cardiology centers. Primary endpoints were procedural success and safety. Secondary endpoints were closure rate and clinical safety at 1-month follow-up.
RESULTS: Patients' age and weight were 8.2 ± 3.9 years (range 3-21, median 9.9) and 29.6 ± 15.3 kg (range 16-57, median 33.3), respectively. ASD diameter was 16.6 ± 4.5 mm (median 10), resulting in QP/QS of 1.7 ± 0.7 (median 1.6). Seventeen pts. (39.5%) were considered "surgical" candidates due to challenging septum morphology, ASD rim deficiency or ASD diameter/patient weight ratio ≥ 1.2. Device placement was successfully achieved in all but one patient (97.7%), in whom it embolized early after deployment, resulting in rescue surgical repair. No cross-over with different devices was recorded. Median procedure and fluoroscopy times were 40 and 6.8 min, respectively. Major adverse events were recorded in 7.0% (3 pts). Complete closure rate was 78.5% at discharge, rising to 92.9% (39/42 pts) at 1 month evaluation, without cardiac or extra-cardiac adverse events. "Challenging" procedures were more time-consuming but as effective and safe as the "simple" ones.
CONCLUSIONS: The GORE® Cardioform ASD Occluder device was highly effective and versatile in closure of ASDs with different anatomy and size, even in challenging settings.

PMID: 33220363 [PubMed - as supplied by publisher]

Icon for Springer Related Articles

Longitudinal diastolic strain slope as an early sign for systolic dysfunction among patients with active cancer.

Clin Res Cardiol. 2020 Nov 21;:

Authors: Hochstadt A, Arnold J, Rosen R, Sherez C, Sherez J, Mor L, Moshkovits Y, Merdler I, Szekely Y, Arbel Y, Rozenbaum Z, Kapusta L, Topilsky Y, Laufer-Perl M

Abstract
BACKGROUND: Diastolic dysfunction is a common finding in patients receiving cancer therapy. This study evaluated the correlation of diastolic strain slope (Dss) with routine echocardiography diastolic parameters and its role in early detection of systolic dysfunction and cardiovascular (CV) mortality within this population.
METHODS: Data were collected from the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling adult patient receiving cancer therapy. All patients performed at least three echocardiography exams (T1, T2, T3), including left ventricle Global Longitudinal Strain (LV GLS) and Dss. Systolic dysfunction was determined by either LV GLS relative reduction of ≥ 15% or LV ejection fraction reduction > 10% to < 53%. Dss was assessed as the early lengthening rate, measured by the diastolic slope (delta%/sec).
RESULTS: Among 144 patients, 114 (79.2%) were female with a mean age of 57.31 ± 14.3 years. Dss was significantly correlated with e' average. Mid segment Dss change between T1 and T2 showed significant association to systolic dysfunction development (Odds Ratio (OR) = 1.04 [1.01,1.06]. p = 0.036). In multivariate prediction, Dss increase was a significant predictor for the development of systolic dysfunction (OR = 1.06 [1.03,1.1], P < 0.001).An 8% increase in Dss between T1 and T2 was associated with a trend in increased CV mortality (HR = 3.4 [0.77,15.4], p = 0.085).
CONCLUSIONS: This study is the first to use the novel measurement of Dss in patients treated with cancer therapies and to show significant correlation between routine diastolic dysfunction parameters and Dss. Changes in the mid segment were found to have significant independent early predictive value for systolic dysfunction development in univariate and multivariate analyses.

PMID: 33219853 [PubMed - as supplied by publisher]

Icon for Springer Related Articles

Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases.

Pediatr Cardiol. 2020 Nov 21;:

Authors: Shi H, Yang S, Lin N, Huang P, Yu R, Chen M, Wang L, Jiang Z, Sun X

Abstract
The aim of this study is to evaluate the relationship between maternal single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine (HCY) level and offspring congenital heart diseases (CHDs). 338 mothers with offspring CHDs as case group and 306 mothers of normal children as control group were recruited. Their pregnant histories were interviewed by questionnaire and the MTHFR rsl801133 and rsl801131 were genotyped. The case-control analysis was used to find out the relationship between maternal SNPs of MTHFR gene and offspring CHDs. And the plasma HCY concentration of the mothers of CHDs children was detected. This case-case study was intended to find out the relevance between maternal HCY level and SNPs of MTHFR gene. There were significant differences in the gender of children, occupation of mothers, family history with CHDs, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHDs group and control group (P < 0.05). MTHFR rs1801133 was significantly associated with their offspring CHDs in mothers. The polymorphism of maternal MTHFR rs1801133 increased plasma HCY level, especially the homozygous mutation. Besides the environmental factors, our results suggested that the maternal MTHFR rs1801133 polymorphism might be a risk factor of their offspring CHDs, which may be due to the hyperhomocysteinemia by abnormal metabolism of HCY.

PMID: 33219830 [PubMed - as supplied by publisher]

Icon for Springer Related Articles

Prenatal diagnosis, associated findings and postnatal outcome in fetuses with congenitally corrected transposition of the great arteries.

Arch Gynecol Obstet. 2020 Nov 20;:

Authors: Krummholz A, Gottschalk I, Geipel A, Herberg U, Berg C, Gembruch U, Hellmund A

Abstract
PURPOSE: To analyze anatomic features and associated malformations in 37 prenatally detected cases of congenitally corrected transposition of the great arteries (ccTGA) and to evaluate the prenatal course, neonatal outcome and mid-term follow-up.
METHODS: Retrospective analysis of prenatal ultrasound of 37 patients with ccTGA in two tertiary centers between 1999 and 2019. All fetuses received fetal echocardiography and a detailed anomaly scan. Postnatal outcome and follow-up data were retrieved from pediatric reports.
RESULTS: Isolated ccTGA without associated cardiac anomalies was found in 13.5% (5/37), in all other fetuses additional defects such as VSD (73.0%), pulmonary obstruction (35.1%), tricuspid valve anomalies (18.9%), aortic arch anomalies (13.5%), ventricular hypoplasia (5.4%) or atrioventricular block (5.4%) were present. The rate of extracardiac malformations or chromosomal aberrations was low. There were 91.9% (34/37) live births and postnatal survival rates reached 91.2% in a mean follow-up time of 4.98 years. The prenatal diagnosis of ccTGA was confirmed postnatally in all but one documented live birth and the prenatal counselling regarding the expected treatment after birth (uni- versus biventricular repair) was reassured in the majority of cases. The postnatal intervention rate was high, 64.7% (22/34) received surgery, the intervention-free survival was 36.7%, 35.0% and 25.0% at 1 month, 1 year and 10 years, respectively.
CONCLUSIONS: ccTGA is a rare heart defect often associated with additional heterogeneous cardiac anomalies that can be diagnosed prenatally. The presented study demonstrates a favorable outcome in most cases but the majority of patients require surgical treatment early in life.

PMID: 33219483 [PubMed - as supplied by publisher]

Related Articles

Cortical hyperostosis, rare adverse effect of prostaglandin.

Med J Malaysia. 2020 Nov;75(6):748-749

Authors: Ng RL, Koay HS, Jamil MT

Abstract
We describe here an infant girl with ductal dependent complex cyanotic heart disease, who required prostaglandin infusion for a total of five months prior to Blalock-Taussig shunt procedure. Her alkaline phosphatase activity was raised after seven weeks being on prostaglandin and only dropped to the normal range seven days after discontinuing prostaglandin infusion. During our review at five months old, her limbs were grossly swollen and radiographic examination showed dense periosteal reaction in the long bones. Based on the clinical findings and investigations, she was diagnosed to have cortical hyperostosis, which is an uncommon side effect of prostaglandin. She underwent right Blalock-Taussig Shunt procedure successfully with no major complications. Unfortunately, she succumbed to infection two months after surgery.

PMID: 33219191 [PubMed - in process]

Icon for Elsevier Science Related Articles

Effect of In Utero Non-Steroidal Anti-Inflammatory Drug Therapy for Severe Ebstein Anomaly or Tricuspid Valve Dysplasia (NSAID therapy for fetal Ebstein anomaly).

Am J Cardiol. 2020 Nov 17;:

Authors: Freud LR, Wilkins-Haug LE, Beroukhim RS, LaFranchi T, Phoon CK, Glickstein JS, Cumbermack KM, Makhoul M, Morris SA, Sun HY, Ferrer Q, Pedra SR, Tworetzky W

Abstract
Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) are rare congenital malformations associated with nearly 50% mortality when diagnosed in utero. The diseases often produce severe tricuspid regurgitation (TR) in the fetus and in some cases, pulmonary regurgitation (PR) and circular shunting ensue. Since the ductus arteriosus (DA) plays a critical role in the circular shunt and may be constricted by transplacental non-steroidal anti-inflammatory drugs (NSAIDs), we sought to assess the effect of NSAIDs on fetuses with EA/TVD. We reviewed mothers of singleton fetuses with EA/TVD and PR, indicative of circular shunting, who were offered NSAIDs at multiple centers from 2010-2018. Initial dosing consisted of indomethacin, followed by ibuprofen in most cases. Twenty-one patients at 10 centers were offered therapy at a median gestational age (GA) of 30.0 weeks (range: 20.9-34.9). Most (15/21=71%) mothers received NSAIDs, and 12/15 (80%) achieved DA constriction after a median of 2.0 days (1.0-6.0). All fetuses with DA constriction had improved PR; 92% had improved Doppler patterns. Median GA at pregnancy outcome was 36.1 weeks (30.7-39.0) in fetuses with DA constriction vs. 33 weeks (23.3-37.3) in fetuses who did not receive NSAIDs or achieve DA constriction (p=0.040). Eleven of 12 patients (92%) with DA constriction survived to live-birth, whereas 4/9 patients (44%) who did not receive NSAIDs or achieve DA constriction survived (p=0.046). In conclusion, our findings demonstrate the proof of concept that NSAIDs mitigate circular shunt physiology by DA constriction and improve PR among fetuses with severe EA/TVD. Although the early results are encouraging, further investigation is necessary to determine safety and efficacy.

PMID: 33217351 [PubMed - as supplied by publisher]

Icon for Atypon Related Articles

Sinus node disfunction in an adolescent with systemic lupus erythematosus.

Lupus. 2020 Nov 20;:961203320974091

Authors: Fogaça da Mata M, Rebelo M, Sousa HS, Rocha A, Miguel P, Oliveira Ramos F, Costa-Reis P

Abstract
Cardiac involvement in systemic lupus erythematosus (SLE) is well documented. The pericardium, myocardium and endocardium, as well as the coronary arteries, the valves and the conduction system can all be affected. While pericarditis is common, arrythmias are less frequently described.We present a 13-year-old male, who had fatigue, anorexia, weight loss, myalgias and arthralgias for four months. On physical examination, we identified bradycardia (heart rate 31-50 bpm), oral and nasal ulcers and polyarthritis. The laboratory results showed hemolytic anemia, hypocomplementemia, antinuclear and anti-dsDNA antibodies, hematuria and non-nephrotic proteinuria. Renal function was normal. Lupus nephritis class II was diagnosed by kidney biopsy. On the transthoracic echocardiogram we identified a minimal pericardial effusion, suggesting pericarditis, and, on the electrocardiogram, we detected sinus arrest with junctional rhythm, denoting sinus node dysfunction. The patient was diagnosed with juvenile SLE with cardiac, renal, musculoskeletal and hematologic involvement. Disease remission and cardiac rhythm control were obtained with steroids and mycophenolate mofetil. Currently, the patient is asymptomatic, with normal sinus rhythm.We described an adolescent with SLE who had sinus node dysfunction upon diagnosis. Other cases have been reported in adults but none in juvenile SLE. All SLE patients should have a thorough cardiac examination to promptly diagnose and treat the innumerous cardiac manifestations of this disease.

PMID: 33215560 [PubMed - as supplied by publisher]

Icon for Georg Thieme Verlag Stuttgart, New York Icon for Georg Thieme Verlag Stuttgart, New York Icon for PubMed Central Related Articles

Sirolimus for Kaposiform Hemangioendothelioma and Kasabach-Merritt Phenomenon in a Neonate.

AJP Rep. 2020 Oct;10(4):e390-e394

Authors: Cabrera TB, Speer AL, Greives MR, Goff DA, Menon NM, Reynolds EW

Abstract
We present a case of a neonate born with kaposiform hemangioendothelioma (KHE), complicated by Kasabach-Merritt phenomenon (KMP) and other serious conditions, who was successfully treated with sirolimus. In addition to complications from thrombocytopenia and fluid overload, during the course of therapy, our patient experienced supratherapeutic drug levels at the commonly accepted starting dose of sirolimus. Patients with KHE and KMP should be closely monitored for potential complications of both the initial disease and unexpected side effects of treatments.

PMID: 33214934 [PubMed]

Related Articles

Fifteen-minute consultation: Neonatal hypertension.

Arch Dis Child Educ Pract Ed. 2020 Nov 19;:

Authors: Singh Y, McGeoch L, Job S

Abstract
Neonatal hypertension is a rare but well recognised condition, especially in newborns needing invasive monitoring in the intensive care unit. Recognition of newborns with hypertension remains challenging because of natural variability in blood pressure with postconceptional age and the lack of reference data for different gestational ages. Investigation of neonates with hypertension can be challenging in light of the myriad differing aetiologies. This may be simplified by a systematic approach to investigation. There remains a relative paucity of data to guide the use of pharmacological therapies for hypertension in neonates. Clinicians rely on empirical management protocols based on experience and expert opinion. Much of the information on dosing regimens and protocols has simply been derived from the use of antihypertensive agents in older children and in adults, despite fundamental pathophysiological differences.

PMID: 33214239 [PubMed - as supplied by publisher]

Icon for Elsevier Science Related Articles

Genotype Predicts Outcomes in Fetuses and Neonates With Severe Congenital Long QT Syndrome.

JACC Clin Electrophysiol. 2020 Nov;6(12):1561-1570

Authors: Moore JP, Gallotti RG, Shannon KM, Bos JM, Sadeghi E, Strasburger JF, Wakai RT, Horigome H, Clur SA, Hill AC, Shah MJ, Behere S, Sarquella-Brugada G, Czosek R, Etheridge SP, Fischbach P, Kannankeril PJ, Motonaga K, Landstrom AP, Williams M, Patel A, Dagradi F, Tan RB, Stephenson E, Krishna MR, Miyake CY, Lee ME, Sanatani S, Balaji S, Young ML, Siddiqui S, Schwartz PJ, Shivkumar K, Ackerman MJ

Abstract
OBJECTIVES: This study sought to determine the relationship between long QT syndrome (LQTS) subtype (LTQ1, LTQ2, LTQ3) and postnatal cardiac events (CEs).
BACKGROUND: LQTS presenting with 2:1 atrioventricular block or torsades de pointes in the fetus and/or neonate has been associated with risk for major CEs, but overall outcomes and predictors remain unknown.
METHODS: A retrospective study involving 25 international centers evaluated the course of fetuses/newborns diagnosed with congenital LQTS and either 2:1 atrioventricular block or torsades de pointes. The primary outcomes were age at first CE after dismissal from the newborn hospitalization and death and/or cardiac transplantation during follow-up. CE was defined as aborted cardiac arrest, appropriate shock from implantable cardioverter-defibrillator, or sudden cardiac death.
RESULTS: A total of 84 fetuses and/or neonates were identified with LQTS (12 as LQT1, 35 as LQT2, 37 as LQT3). Median gestational age at delivery was 37 weeks (interquartile range: 35 to 39 weeks) and age at hospital discharge was 3 weeks (interquartile range: 2 to 5 weeks). Fetal demise occurred in 2 and pre-discharge death in 1. Over a median of 5.2 years, there were 1 LQT1, 3 LQT2, and 23 LQT3 CEs (13 aborted cardiac arrests, 5 sudden cardiac deaths, and 9 appropriate shocks). One patient with LQT1 and 11 patients with LQT3 died or received cardiac transplant during follow-up. The only multivariate predictor of post-discharge CEs was LQT3 status (LQT3 vs. LQT2: hazard ratio: 8.4; 95% confidence interval: 2.6 to 38.9; p < 0.001), and LQT3, relative to LQT2, genotype predicted death and/or cardiac transplant (p < 0.001).
CONCLUSIONS: In this large multicenter study, fetuses and/or neonates with LQT3 but not those with LQT1 or LQT2 presenting with severe arrhythmias were at high risk of not only frequent, but lethal CEs.

PMID: 33213816 [PubMed - in process]

Icon for BioMed Central Icon for PubMed Central Related Articles

Global prevalence of congenital heart disease in school-age children: a meta-analysis and systematic review.

BMC Cardiovasc Disord. 2020 Nov 19;20(1):488

Authors: Liu Y, Chen S, Zühlke L, Babu-Narayan SV, Black GC, Choy MK, Li N, Keavney BD

Abstract
BACKGROUND: Congenital heart disease (CHD) is the commonest birth defect. Studies estimating the prevalence of CHD in school-age children could therefore contribute to quantifying unmet health needs for diagnosis and treatment, particularly in lower-income countries. Data at school age are considerably sparser, and individual studies have generally been of small size. We conducted a literature-based meta-analysis to investigate global trends over a 40-year period.
METHODS AND RESULTS: Studies reporting on CHD prevalence in school-age children (4-18 years old) from 1970 to 2017 were identified from PubMed, EMBASE, Web of Science and Google Scholar. According to the inclusion criteria, 42 studies including 2,638,475 children, reporting the prevalence of unrepaired CHDs (both pre-school diagnoses and first-time school-age diagnoses), and nine studies including 395,571 children, specifically reporting the prevalence of CHD first diagnosed at school ages, were included. Data were combined using random-effects models. The prevalence of unrepaired CHD in school children during the entire period of study was 3.809 (95% confidence intervals 3.075-4.621)/1000. A lower proportion of male than female school children had unrepaired CHD (OR = 0.84 [95% CI 0.74-0.95]; p = 0.001). Between 1970-1974 and 1995-1999, there was no significant change in the prevalence of unrepaired CHD at school age; subsequently there was an approximately 2.5-fold increase from 1.985 (95% CI 1.074-3.173)/1000 in 1995-1999 to 4.832 (95% CI 3.425-6.480)/1000 in 2010-2014, (p = 0.009). Among all CHD conditions, atrial septal defects and ventricular septal defects chiefly accounted for this increasing trend. The summarised prevalence (1970-2017) of CHD diagnoses first made in childhood was 1.384 (0.955, 1.891)/1000; during this time there was a fall from 2.050 [1.362, 2.877]/1000 pre-1995 to 0.848 [0.626, 1.104]/1000 in 1995-2014 (p = 0.04).
CONCLUSIONS: Globally, these data show an increased prevalence of CHD (mainly mild CHD conditions) recognised at birth/infancy or early childhood, but remaining unrepaired at school-age. In parallel there has been a decrease of first-time CHD diagnoses in school-age children. These together imply a favourable shift of CHD recognition time to earlier in the life course. Despite this, substantial inequalities between higher and lower income countries remain. Increased healthcare resources for people born with CHD, particularly in poorer countries, are required.

PMID: 33213369 [PubMed - in process]

Related Articles

Atherosclerotic Process in Seroreverter Children and Adolescents Exposed to Fetal Antiretroviral Therapy.

Curr HIV Res. 2020 Nov 18;:

Authors: Martins P, Pires A, Santos JL, Sena C, Seiça R

Abstract
BACKGROUND: Human immunodeficiency virus infection is a recognized risk factor for premature atherosclerosis in children and adolescents. However, the atherosclerotic process in uninfected children exposed in utero to the virus and antiretroviral therapy is less clear.
OBJECTIVE: To determine the potential cardiovascular risk associated to this in utero milieu exposition.
MATERIAL AND METHODS: A total of 115 individuals were studied (77 in the sample group and 38 controls). Eighteen analytical mediators involved in the atherogenic pathways (metabolic dysregulation, inflammation and prothrombotic state) were analyzed. The carotid intima-media thickness, which is a subclinical marker of atherosclerosis, was also measured.
RESULTS: No significant statistical differences were identified between the sample and control groups, either in the biochemical or the echographic markers.
CONCLUSION: In utero exposure to the HIV virus and antiretroviral therapy in uninfected children and adolescents is not correlated to accelerated atherosclerosis.

PMID: 33213356 [PubMed - as supplied by publisher]

Icon for Nature Publishing Group Icon for PubMed Central Related Articles

CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module.

Nat Commun. 2020 11 02;11(1):5520

Authors: Dougherty GW, Mizuno K, Nöthe-Menchen T, Ikawa Y, Boldt K, Ta-Shma A, Aprea I, Minegishi K, Pang YP, Pennekamp P, Loges NT, Raidt J, Hjeij R, Wallmeier J, Mussaffi H, Perles Z, Elpeleg O, Rabert F, Shiratori H, Letteboer SJ, Horn N, Young S, Strünker T, Stumme F, Werner C, Olbrich H, Takaoka K, Ide T, Twan WK, Biebach L, Große-Onnebrink J, Klinkenbusch JA, Praveen K, Bracht DC, Höben IM, Junger K, Gützlaff J, Cindrić S, Aviram M, Kaiser T, Memari Y, Dzeja PP, Dworniczak B, Ueffing M, Roepman R, Bartscherer K, Katsanis N, Davis EE, Amirav I, Hamada H, Omran H

Abstract
Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45-/- mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module.

PMID: 33139725 [PubMed - indexed for MEDLINE]

Icon for Public Library of Science Icon for PubMed Central Related Articles

The impact of impending / onset of vision loss on depression, anxiety, and vision-related quality of life in Birdshot-Retinochoroiditis and Serpiginous Choroiditis.

PLoS One. 2020;15(10):e0239210

Authors: Pohlmann D, Barth A, Macedo S, Pleyer U, Winterhalter S, Albayrak Ö

Abstract
To evaluate the impact of Birdshot-Retinochoroidopathy (BSRC) and Serpiginous Choroiditis (SC) on depression, anxiety, and vision-related quality of life. 72 individuals (BSRC: n = 28, SC: n = 8; healthy control group (HC): n = 36) completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the Visual Function Questionnaire (VFQ-25). Multivariate linear regression models were used to analyze different subscales of the PHQ-9, the GAD-7 and the VFQ-25. The results showed that the mean of PHQ-9 was significantly higher while the mean of the VFQ-25 and its´ subscales were consistently lower in the disease group compared to HC. The mean of GAD-7 was not significantly lower in the disease group compared to HC. Stratification for different disease severity stages and duration of disease did not reveal any differences in sum scores of PHQ-9, GAD-7, and VFQ-25, whereas there were significant differences in some subscales of the VFQ-25. We conclude that BSRC and SC patients show higher levels of depression and a reduced visual quality of life due to imminent loss of vision. Because depression and quality of life are adversely affected by lack of social contacts and functioning, psychological treatment should enable patients to maintain their independence and ability to social interaction. Psychosomatic care should be taken in account for the treatment of BSRC and SC.

PMID: 33017403 [PubMed - indexed for MEDLINE]

Library News

Image result for new Library Discovery Tool

Check out our guide for a brief overview, how to access and use the Discovery tool. Trouble accessing or have questions?  Please contact us

BMJ Best Practice, clinical decision support tool is now available. Access it on the Trust intranet without any password, to access remotely login with NHS OpenAthens, download the app to access on mobile devices anywhere. See the  user guide for details.

BBC News- Health

People arriving in England can end their self-isolation with a negative test taken after five days.
People have tendency to soldier on, potentially making colleagues sick, health secretary says.
We answer some of your questions about the Oxford vaccine.
Nearly 14,000 deaths occurred in the week ending 13 November - with 3,000 linked to Covid.
Several vaccines are showing promise and one is already being reviewed by the UK regulator.

Accessing Articles
Articles from journals marked in green are freely available or available in print in the library, or are available by using your NHS Athens account. You may need to click on 'Log in with Athens' to get an Athens login box.

If you don't have an NHS Athens account, you can register online, and if you do this on an NHS PC, you'll receive a confirmation email the same day.

Journals marked in orange aren't available online, but we hold print copies in the Library.

Journals marked in red aren't available online or in the Library but we can order articles  via our Inter Library Loan Service. There is a small charge for this. Please contact the library on ext 5968 or email Library.InfoService@chelwest.nhs.uk  for more information.

Quick Links
qrcode.14118297[1]