Journal Watch

College students with congenital heart disease: A critical time for transition.

J Am Coll Health. 2018 Feb 16;:0

Authors: Hardy RY, Gurvitz M, Jackson JL, May S, Miller P, Daskalov R, Foster E

PMID: 29452064 [PubMed - as supplied by publisher]

Variant in human POFUT1 reduces enzymatic activity and likely causes a recessive microcephaly, global developmental delay with cardiac and vascular features.

Glycobiology. 2018 Feb 14;:

Authors: Takeuchi H, Wong D, Schneider M, Freeze HH, Takeuchi M, Berardinelli SJ, Ito A, Lee H, Nelson SF, Haltiwanger RS

Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis, and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood. Here we report a patient with a congenital syndrome consisting of severe global developmental delay, microcephaly, heart defects, failure to thrive, and liver disease with a previously unreported homozygous NM_015352.1: c.485 C>T variant (p.Ser162Leu) in POFUT1 detected by exome sequencing. Both parents are heterozygotes and neither manifests any signs of DDD. No other detected variant explained the phenotype. This variant eliminated a conserved N-glycosylation sequon at Asn160 in POFUT1 and profoundly decreased POFUT1 activity in patient fibroblasts compared to control fibroblasts. Purified p.Ser162Leu mutant protein also showed much lower POFUT1 activity with a lower affinity for EGF acceptor substrate than wild type POFUT1. Eliminating the N-glycan sequon by replacing Asn160 with Gln had little effect on POFUT1 activity, suggesting that loss of the glycan is not responsible for the defect. Furthermore, the p.Ser162Leu mutant showed weaker ability to rescue Notch activity in cell-based assays. These results suggest that this N-glycan of POFUT1 is not required for its proper enzymatic function, and that the p.Ser162Leu mutation of POFUT1 likely causes global developmental delay, microcephaly with vascular and cardiac defects.

PMID: 29452367 [PubMed - as supplied by publisher]

Related Articles

Incidence and natural history of neonatal isolated ventricular septal defects: Do we know everything? A 6-year single-center Italian experience follow-up.

Congenit Heart Dis. 2018 Jan;13(1):105-112

Authors: Cresti A, Giordano R, Koestenberger M, Spadoni I, Scalese M, Limbruno U, Falorini S, Stefanelli S, Picchi A, De Sensi F, Malandrino A, Cantinotti M

BACKGROUND: Despite ventricular septal defects (VSDs) are the most common congenital heart diseases (CHDs) in the neonatal period, their incidence and natural history are still debated and their follow-up and management strategies remain controversial. Our aim was to evaluate the incidence and natural history of isolated VSDs.
METHODS: From January 1996 to December 2015 all neonates with a CHD suspicion were referred to the Cardiological Department of Grosseto Misericordia Hospital. Only newborns with confirmed isolated VSD were enrolled in this study and followed for 6 years.
RESULTS: Our 343 newborns with an isolated VSD (incidence of 10.45/1000/births) account for 64% of all detected CHDs. VSDs location were as follows: muscular (73.8%), perimembranous (11.3%), inlet (1%), and outlet (0.8%). Of the located VSDs, 90% were small, 7.5% moderate, and 2.5% large, respectively. Spontaneous closure was observed in 96 (29.2%) of the VSD patients at 6-month, 198 (60.2%) at 1-year, 261 (79.3%) at 2-year, and in 302 (91.8%) at 6-year follow-up. Risk factors for defect persistence were a perimembranous location (P = .001; HR: 0.508, CI: 0.342-0.755), detection of multiple defects (P = .043; HR: 0.728, CI: 0.536-0.990), and male gender (P < .048; HR: 0.783, CI: 0.615-0.998), respectively.
CONCLUSIONS: We here provide an incidence and natural history of neonatal isolated VSDs in a neonatal Caucasian population. These data may be useful for the development of expert consensus/standard recommendation guidelines for the follow-up and VSD management, data that are currently lacking.

PMID: 28857497 [PubMed - indexed for MEDLINE]

Related Articles

Resource reduction in pediatric chest pain: Standardized clinical assessment and management plan.

Congenit Heart Dis. 2018 Jan;13(1):46-51

Authors: Saleeb SF, McLaughlin SR, Graham DA, Friedman KG, Fulton DR

OBJECTIVE: Using a Standardized Clinical Assessment and Management Plan (SCAMP) for pediatric patients presenting to clinic with chest pain, we evaluated the cost impact associated with implementation of the care algorithm. Prior to introduction of the SCAMP, we analyzed charges for 406 patients with chest pain, seen in 2009, and predicted 21% reduction of overall charges had the SCAMP methodology been used. The SCAMP recommended an echocardiogram for history, examination, or ECG findings suggestive of a cardiac etiology for chest pain.
DESIGN: Resource utilization was reviewed for 1517 patients (7-21 years) enrolled in the SCAMP from July 2010 to April 2014.
RESULTS: Compared to the 2009 historic cohort, patients evaluated by the SCAMP had higher rates of exertional chest pain (45% vs 37%) and positive family history (5% vs 1%). The SCAMP cohort had fewer abnormal physical examination findings (1% vs 6%) and abnormal electrocardiograms (3% vs 5%). Echocardiogram use increased in the SCAMP cohort compared to the 2009 historic cohort (45% vs 41%), whereas all other ancillary testing was reduced: exercise stress testing (4% SCAMP vs 28% historic), Holter (4% vs 7%), event monitors (3% vs 10%), and MRI (1% vs 2%). Total charges were reduced by 22% ($822 625) by use of the Chest Pain SCAMP, despite a higher percentage of patients for whom echocardiogram was recommended compared to the historic cohort.
CONCLUSIONS: The Chest Pain SCAMP effectively streamlines cardiac testing and reduces resource utilization. Further reductions can be made by algorithm refinement regarding echocardiograms for exertional symptoms.

PMID: 28944584 [PubMed - indexed for MEDLINE]

Related Articles

Time course of the changes in right and left ventricle function and associated factors after transcatheter closure of atrial septal defects.

Congenit Heart Dis. 2018 Jan;13(1):131-139

Authors: Yoo BW, Kim JO, Eun LY, Choi JY, Kim DS

OBJECTIVE: The purpose of this study was to evaluate the changes in right ventricle (RV) and left ventricle (LV) function after transcatheter atrial septal defect (ASD) closure and to assess the influence of the age and the amount of shunt.
DESIGN: Retrospective study PATIENTS: Fifty-three adult patients who underwent transcatheter closure were enrolled, then divided into subgroups according to the age (< 40 years vs ≥ 40 years), and the amount of shunt flow (QpQs < 2.5 vs QpQs ≥ 2.5).
OUTCOME MEASURES: Two-dimensional tissue Doppler imaging was performed in a four-chamber view at the basal ventricular septum (VS) and tricuspid valve annulus (TVA) before and at 1 month and 6 months after closure. Myocardial velocities, the myocardial performance index (MPI), and isovolumic acceleration (IVA) were assessed.
RESULTS: At the TVA, the MPI decreased slightly and then greatly increased at 6 months after closure (P = .002). The IVA improved in all patients (P < .001), and the E'/A' ratio decreased, especially in the old age group (P = .031) and larger shunt group (P = .035). At the VS, S' and the IVA decreased and had not recovered until 6 months in the old age (P = .02) and larger shunt (P = .02). The Qp/Qs showed a significant reverse correlation with a decrease in the E'/A' at the TVA (r = -0.37, P = .008), and age of patient was correlated with a decrease in the IVA at the VS (r = -0.32, P = .019). The age at closure (β = -0.36, P = .002), the Qp/Qs ratio (β = -0.45, P = .01), and RV MPI changes (β = -7.64, P < .001) were found to be associated factors with IVA decrease at the VS.
CONCLUSIONS: After ASD closure, RV global function might be impaired. In elderly patients and patients with a large shunt, impairment of LV contractility developed until 6 months after closure. Close long-term observation is required after closure, especially in old-age patients with a large shunt.

PMID: 28944616 [PubMed - indexed for MEDLINE]

Related Articles

Comparison of valvar and right ventricular function following transcatheter and surgical pulmonary valve replacement.

Congenit Heart Dis. 2018 Jan;13(1):140-146

Authors: Li WF, Pollard H, Karimi M, Asnes JD, Hellenbrand WE, Shabanova V, Weismann CG

OBJECTIVE: Trans-catheter (TC) pulmonary valve replacement (PVR) has become common practice for patients with right ventricular outflow tract obstruction (RVOTO) and/or pulmonic insufficiency (PI). Our aim was to compare PVR and right ventricular (RV) function of patients who received TC vs surgical PVR.
DESIGN: Retrospective review of echocardiograms obtained at three time points: before, immediately after PVR, and most recent.
PATIENTS: Sixty-two patients (median age 19 years, median follow-up 25 months) following TC (N = 32) or surgical (N = 30) PVR at Yale-New Haven Hospital were included.
OUTCOME MEASURES: Pulmonary valve and right ventricular function before, immediately after, and most recently after PVR.
RESULTS: At baseline, the TC group had predominant RVOTO (74% vs 10%, P < .001), and moderate-severe PI was less common (61% vs 100%, P < .001). Immediate post-procedural PVR function was good throughout. At last follow-up, the TC group had preserved valve function, but the surgical group did not (moderate RVOTO: 6% vs 41%, P < .001; >mild PI: 0% vs 24%, P = .003). Patients younger than 17 years at surgical PVR had the highest risk of developing PVR dysfunction, while PVR function in follow-up was similar in adults. Looking at RV size and function, both groups had a decline in RV size following PVR. However, while RV function remained stable in the TC group, there was a transient postoperative decline in the surgical group.
CONCLUSIONS: TC PVR in patients age <17 years is associated with better PVR function in follow-up compared to surgical valves. There was a transient decline in RV function following surgical but not TC PVR. TC PVR should therefore be the first choice in children who are considered for PVR, whenever possible.

PMID: 29148206 [PubMed - indexed for MEDLINE]

Related Articles

Using a statewide survey methodology to prioritize pediatric cardiology core content.

Congenit Heart Dis. 2018 Jan;13(1):147-153

Authors: Neal AE, Lehto E, Miller KH, Ziegler C, Davis E

OBJECTIVE: Although pediatrician-reported relevance of Canadian cardiology-specific objectives has been studied, similar data are not available for the 2016 American Board of Pediatrics (ABP) cardiology-specific objectives. This study asked Kentucky trainees, pediatricians, and pediatric cardiologists to identify "most important" content within these objectives.
DESIGN, METHODS, OUTCOME MEASURES: This cross-sectional study used an original, online survey instrument based on the 2016 ABP cardiology-specific objectives. We collected quantitative data (numerical indications of importance) and qualitative data (open-ended replies regarding missing content and difficulty in teaching and learning). Respondents indicated the top two choices of most important items within eight content areas. Descriptive statistics (frequencies and percentages) and chi-square analysis were calculated. Content within categories was organized using naturally occurring "clusters" and "gaps" in scores. Common themes among open-ended qualitative responses were identified using Pandit's version of Glaser and Strauss Grounded theory (constant comparison).
RESULTS: Of the 136 respondents, 23 (17%) were residents, 15 (11%) fellows, 85 (62%) pediatricians, and 13 (10%) pediatric cardiologists. Of attendings, 80% reported faculty/gratis faculty status. Naturally occurring clusters in respondent-designated importance resulted in ≤3 "most selected" objectives per content area. Objectives in "most selected" content pertained to initial diagnosis (recognition of abnormality/disease) (n = 16), possible emergent/urgent intervention required (n = 14), building a differential (n = 8), and planning a workup (n = 4). Conversely, themes for "least selected" content included comanagement with subspecialist (n = 15), knowledge useful in patient-family communication (n = 9), knowledge that can be referenced (as needed) (n = 7), and longitudinal/follow-up concerns (n = 5).
CONCLUSIONS: This study demonstrated the utility of an online survey methodology to identify pediatric cardiology content perceived most important. Learners and faculty generally provided concordant responses regarding most important content within the cardiology-specific ABP objectives. Medical educators could apply this methodology to inform curriculum revision.

PMID: 29181874 [PubMed - indexed for MEDLINE]

Related Articles

Arrhythmia after cone repair for Ebstein anomaly: The Mayo Clinic experience in 143 young patients.

Congenit Heart Dis. 2018 Jan;13(1):26-30

Authors: Wackel P, Cannon B, Dearani J, Sessions K, Holst K, Johnson J, Cetta F

BACKGROUND: The increased incidence of preoperative and postoperative arrhythmia in Ebstein anomaly (EA) prompted some clinicians to perform an electrophysiology study (EPS) in all patients prior to surgery for EA. The cone repair (CR) is the current surgical option of choice for most young patients with EA but the effect of the CR on arrhythmia is not well established.
OBJECTIVES: To assess the burden of arrhythmia in young patients after CR and to assess the utility of selective preoperative EPS.
MATERIALS AND METHODS: A retrospective review of all patients <21 years of age with EA who had a CR at Mayo Clinic from June 2007 to December 2015 was performed. Surveys were mailed and telephone calls were made to all individuals to assess antiarrhythmic medication use and EP/device procedures performed after CR.
RESULTS: There were 143 patients; median age, 10 years (0.1-20.9 years). Thirty-five (24%) patients had a preoperative EPS of which 26 (18%) had a preoperative ablation. Indications for EPS were Wolff-Parkinson-White (WPW), documented arrhythmia, or suspected arrhythmia. Posthospital discharge data were available for 140 (98%) patients. Mean follow-up was 2.9 years (0.1-9.2 years). At follow-up, 7 (5%) patients were receiving antiarrhythmic medications. After CR, only 3 (2%) patients who did not have a preoperative EPS have required an ablation.
CONCLUSIONS: The risk of arrhythmia after CR for EA in young patients is very low when a preoperative EPS is limited to those with WPW, known arrhythmia, or suspected arrhythmia. In smaller patients, it may be reasonable to defer the EPS.

PMID: 29316261 [PubMed - indexed for MEDLINE]

Related Articles

Adolescents and Young Adults Living with Congenital Heart Disease: Coping, Stress Reactivity, and Emotional Functioning.

J Clin Psychol Med Settings. 2018 Feb 17;:

Authors: Monti JD, Jackson JL, Vannatta K

Living with congenital heart disease (CHD) presents survivors with numerous stressors, which may contribute to emotional problems. This study examined (a) whether coping with CHD-related stress predicts symptoms of depression and anxiety, and (b) whether associations between coping and emotional distress are moderated by involuntary stress reactivity. Adolescents and young adults diagnosed with CHD (Mage = 26.4) were recruited from pediatric and adult outpatient cardiology clinics. Participants (N = 168) completed online self-report measures. Hierarchical multiple regression analyses revealed that secondary control coping (e.g., cognitive restructuring, positive thinking) predicted lower depression and anxiety. Primary control coping (e.g., problem-solving) and stress reactivity (e.g., rumination, emotional numbing) interacted to predict depression and anxiety: the higher individuals were in involuntary stress reactivity, the stronger was the association between primary control coping and lower depression and anxiety. These results can inform clinical efforts to prevent or reduce emotional distress among CHD survivors.

PMID: 29455367 [PubMed - as supplied by publisher]

Related Articles

Late-onset choreoathetotic syndrome following heart surgery in adults with end-stage renal disease.

Saudi J Kidney Dis Transpl. 2018 Jan-Feb;29(1):202-206

Authors: Hamzi MA, Hassani K, El Kabbaj D

Choreoathetotic syndrome is a rare complication of open cardiac surgery that is seen usually in children after surgery for congenital cardiac anomalies. Here, we report two cases of adult patients with end-stage renal disease (ESRD) on regular hemodialysis who developed acute choreoathetotic syndrome few days after cardiac surgeries under cardiopulmonary bypass (CPB). Improvement was seen after an interval with complete resolution in one case. Investigations of the cause have been noncontributory. Long CPB time seems to be the main identified risk factor in these cases. One of the unusual features of our adult cases was the existence of ESRD. To the best of our knowledge, this is the first time this complication is described in association with ESRD although the role of this comorbidity in these cases is uncertain.

PMID: 29456231 [PubMed - in process]