Clinical Instructor, Pediatrics - Cardiology
Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: an International Study.
Circulation. Genomic and precision medicine
Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns.An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands.Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia.ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.
View details for DOI 10.1161/CIRCGEN.121.003464
View details for PubMedID 35549293
Loss of Ventricular Pre-excitation During Non-invasive Testing Does Not Exclude High-Risk Accessory Pathways: A Multicenter Study of WPW in Children.
Abrupt loss of ventricular pre-excitation on non-invasive evaluation, or non-persistent pre-excitation, in Wolff-Parkinson-White syndrome (WPW) is thought to indicate a low risk of life-threatening events.To compare accessory pathway (AP) characteristics and occurrences of sudden cardiac arrest (SCA) and rapidly conducted pre-excited atrial fibrillation (RC-AF) in patients with non-persistent and persistent pre-excitation.Patients ≤21 years with WPW and invasive electrophysiology study (EPS) data, SCA, or RC-AF were identified from multicenter databases. Non-persistent pre-excitation was defined as absence/sudden loss of pre-excitation on ECG, Holter, or exercise test. RC-AF was defined as clinical pre-excited atrial fibrillation with shortest pre-excited R-R interval (SPERRI) ≤250ms. AP effective refractory period (APERP), SPERRI at EPS (EPS-SPERRI), and shortest pre-excited paced cycle length (SPPCL) were collected. High-risk APs were defined as APERP, SPERRI, or SPPCL ≤250ms.Of 1589 patients, 244 (15%) had non-persistent pre-excitation and 1345 (85%) had persistent pre-excitation. There were no differences in sex (58 vs 60% male, p=0.49) or age (13.3±3.6 vs 13.1±3.9 years, p=0.43) between groups. Though APERP (344±76 vs 312±61ms, p<0.001), and SPPCL (394±123 vs 317±82ms, p<0.001) were longer in non-persistent versus persistent pre-excitation, there was no difference in EPS-SPERRI (331±71 vs 316±73ms, p=0.15). Non-persistent pre-excitation was associated with fewer high-risk APs (13 vs 23%, p<0.001) than persistent pre-excitation. Of 61 patients with SCA or RC-AF, 6 (10%) had non-persistent pre-excitation (3 SCA, 3 RC-AF).Non-persistent pre-excitation was associated with fewer high-risk APs, though it did not exclude risk of SCA or RC-AF in children with WPW.
View details for DOI 10.1016/j.hrthm.2020.05.035
View details for PubMedID 32497761
Life-Threatening Event Risk in Children With Wolff-Parkinson-White Syndrome: A Multicenter International Study.
JACC. Clinical electrophysiology
2018; 4 (4): 433–44
OBJECTIVES: This study sought to characterize risk in children with Wolff-Parkinson-White (WPW) syndrome by comparing those who had experienced a life-threatening event (LTE) with a control population.BACKGROUND: Children with WPW syndrome are at risk of sudden death.METHODS: This retrospective multicenter pediatric study identified 912 subjects≤21 years of age with WPW syndrome, using electrophysiology (EPS) studies. Case subjects had a history of LTE: sudden death, aborted sudden death, or atrialfibrillation (shortest pre-excited RR interval in atrial fibrillation [SPERRI] of≤250 ms or with hemodynamic compromise); whereas subjects did not. We compared clinical and EPS data between cases and subjects.RESULTS: Case subjects (n= 96) were older and less likely than subjects (n= 816) to have symptoms or documented tachycardia. Mean age at LTE was 14.1 ± 3.9 years of age. The LTE was the sentinel symptom in 65%, consisting of rapidly conducted pre-excited atrial fibrillation (49%), aborted sudden death (45%), and sudden death (6%). Three risk components were considered at EPS: SPERRI, accessory pathway effective refractory period (APERP), and shortest paced cycle length with pre-excitation during atrial pacing (SPPCL), and all were shorter in cases than in control subjects. In multivariate analysis, risk factors for LTE included male sex, Ebstein malformation, rapid anterograde conduction (APERP, SPERRI, or SPPCL≤250 ms), multiple pathways, and inducible atrial fibrillation. Of case subjects, 60 of 86 (69%) had≥2 EPS risk stratification components performed; 22 of 60 (37%) did not have EPS-determined high-risk characteristics, and 15 of 60 (25%) had neither concerning pathway characteristics nor inducible atrioventricular reciprocating tachycardia.CONCLUSIONS: Young patients may experience LTE from WPW syndrome without prior symptoms or markers of high-risk on EPS.
View details for PubMedID 30067481
Atlas-Based Ventricular Shape Analysis for Understanding Congenital Heart Disease.
Progress in pediatric cardiology
2016; 43: 61-69
Congenital heart disease is associated with abnormal ventricular shape that can affect wall mechanics and may be predictive of long-term adverse outcomes. Atlas-based parametric shape analysis was used to analyze ventricular geometries of eight adolescent or adult single-ventricle CHD patients with tricuspid atresia and Fontans. These patients were compared with an "atlas" of non-congenital asymptomatic volunteers, resulting in a set of z-scores which quantify deviations from the control population distribution on a patient-by-patient basis. We examined the potential of these scores to: (1) quantify abnormalities of ventricular geometry in single ventricle physiologies relative to the normal population; (2) comprehensively quantify wall motion in CHD patients; and (3) identify possible relationships between ventricular shape and wall motion that may reflect underlying functional defects or remodeling in CHD patients. CHD ventricular geometries at end-diastole and end-systole were individually compared with statistical shape properties of an asymptomatic population from the Cardiac Atlas Project. Shape analysis-derived model properties, and myocardial wall motions between end-diastole and end-systole, were compared with physician observations of clinical functional parameters. Relationships between altered shape and altered function were evaluated via correlations between atlas-based shape and wall motion scores. Atlas-based shape analysis identified a diverse set of specific quantifiable abnormalities in ventricular geometry or myocardial wall motion in all subjects. Moreover, this initial cohort displayed significant relationships between specific shape abnormalities such as increased ventricular sphericity and functional defects in myocardial deformation, such as decreased long-axis wall motion. These findings suggest that atlas-based ventricular shape analysis may be a useful new tool in the management of patients with CHD who are at risk of impaired ventricular wall mechanics and chamber remodeling.
View details for DOI 10.1016/j.ppedcard.2016.07.010
View details for PubMedID 28082823
Heart rate analysis by sparse representation for acute pain detection
MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING
2016; 54 (4): 595-606
Objective pain assessment methods pose an advantage over the currently used subjective pain rating tools. Advanced signal processing methodologies, including the wavelet transform (WT) and the orthogonal matching pursuit algorithm (OMP), were developed in the past two decades. The aim of this study was to apply and compare these time-specific methods to heart rate samples of healthy subjects for acute pain detection. Fifteen adult volunteers participated in a study conducted in the pain clinic at a single center. Each subject's heart rate was sampled for 5-min baseline, followed by a cold pressor test (CPT). Analysis was done by the WT and the OMP algorithm with a Fourier/Wavelet dictionary separately. Data from 11 subjects were analyzed. Compared to baseline, The WT analysis showed a significant coefficients' density increase during the pain incline period (p < 0.01) and the entire CPT (p < 0.01), with significantly higher coefficient amplitudes. The OMP analysis showed a significant wavelet coefficients' density increase during pain incline and decline periods (p < 0.01, p < 0.05) and the entire CPT (p < 0.001), with suggestive higher amplitudes. Comparison of both methods showed that during the baseline there was a significant reduction in wavelet coefficient density using the OMP algorithm (p < 0.001). Analysis by the two-way ANOVA with repeated measures showed a significant proportional increase in wavelet coefficients during the incline period and the entire CPT using the OMP algorithm (p < 0.01). Both methods provided accurate and non-delayed detection of pain events. Statistical analysis proved the OMP to be by far more specific allowing the Fourier coefficients to represent the signal's basic harmonics and the wavelet coefficients to focus on the time-specific painful event. This is an initial study using OMP for pain detection; further studies need to prove the efficiency of this system in different settings.
View details for DOI 10.1007/s11517-015-1350-3
View details for Web of Science ID 000373021100004
Evaluation and management of bradycardia in neonates and children.
European journal of pediatrics
2016; 175 (2): 151-161
Heart rate is commonly used in pediatric early warning scores. Age-related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. Bradycardia is defined as a heart rate below the lowest normal value for age. Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. As a result of several different etiologies, it may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited sinus node dysfunction or progressive cardiac conduction disorders. Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. The simplest aspect of severe bradycardia management is reflected in the Pediatric and Advanced Life Support (PALS) guidelines.Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current practice for evaluation and management of bradycardia in neonates and children.• Bradycardia is defined as a heart rate below the lowest normal value for age. Age related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. • Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. What is New: • Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Bradycardia may occur in a structurally normal heart or in association with congenital heart disease. Genetic variants in multiple genes have been described. • Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. Early diagnosis and appropriate management are critical in order to prevent sudden death.
View details for DOI 10.1007/s00431-015-2689-z
View details for PubMedID 26780751