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The Brugada pattern is associated with a genetic disorder characterized by ST-segment elevation in the right precordial leads on electrocardiogram (EKG) in the absence of structural heart disease. Patients with the Brugada pattern have an increased risk for ventricular tachyarrhythmia and sudden cardiac death. Loss-of-function mutations in the SCN5A gene which encodes the alpha subunit of the cardiac sodium channel have been associated with Brugada syndrome (BrS). We report a case of a patient who was found to have a spontaneous type 1 Brugada pattern on a routine EKG done prior to travel. He underwent electrophysiological testing (EPS) which provoked ventricular tachycardia and underwent implantable cardioverter defibrillator (ICD) placement. His family history revealed a history of sudden cardiac death, abnormal EKG, syncope, dilated cardiomyopathy, and BrS. Genetic testing revealed a variant of uncertain significance (VUS) in the SCN5A gene in the proband and six of his relatives. The SCN5A VUS in this clinical context and segregation with the disease in his family supports its reclassification to pathogenic.
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INTRODUCTION: Newborn screening for Duchenne muscular dystrophy can be performed via a first-tier creatine kinase-MM measurement followed by reflex testing to second-tier molecular analysis of the DMD gene. In order to establish appropriate cut-offs for the creatine kinase-MM screen, factors that influence creatine kinase-MM in newborns were investigated. MATERIALS AND METHODS: Creatine kinase-MM data from a consented pilot study in New York State were collected over a two-year period and combined with de-identified validation data and analyzed. Univariate analysis and multiple linear regression analysis were performed. RESULTS: The analysis indicated that age of newborn at specimen collection, gestational age and birth weight were significant influencers of CK-MM levels in newborns. In addition, to a lesser extent, sex, race/ethnicity and seasonal temperature also affect CK-MM levels in newborns. CONCLUSIONS: To reduce false positive and false negative cases, newborn screening programs should be cognizant of factors that influence CK-MM when determining cut-offs for the assay. Variability based on age at specimen collection and birth weight are primarily observed within the first week of life. Therefore, particularly during this time period, multi-tiered cut-offs based on age of collection and lower cut-offs for premature and low birth weight babies are recommended. Other cut-off determinants may include sex, race/ethnicity and seasonal temperature.
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Distrofia Muscular de Duchenne , Lactante , Humanos , Recién Nacido , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Tamizaje Neonatal , Peso al Nacer , Proyectos Piloto , Creatina QuinasaRESUMEN
OBJECTIVE: Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre-symptomatic diagnosis. METHODS: At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD. The first-tier screen measured creatine kinase-MM (CK-MM) in dried blood spot specimens submitted for routine NBS. Newborns with elevated CK-MM were referred for genetic counseling and genetic testing. The latter included deletion/duplication analysis and next-generation sequencing (NGS) of the DMD gene followed by NGS for a panel of neuromuscular conditions if no pathogenic variants were detected in the DMD gene. RESULTS: In the two-year pilot study, 36,781 newborns were screened with CK-MM. Forty-two newborns (25 male and 17 female) were screen positive and referred for genetic testing. Deletions or duplications in the DMD gene were detected in four male infants consistent with DMD or Becker muscular dystrophy. One female DMD carrier was identified. INTERPRETATION: This study demonstrated that the state NBS program infrastructure and screening technologies we used are feasible to perform NBS for DMD. With an increasing number of treatment options, the clinical utility of early identification for affected newborns and their families lends support for NBS for this severe disease.
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Distrofia Muscular de Duchenne , Lactante , Humanos , Masculino , Recién Nacido , Femenino , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Tamizaje Neonatal/métodos , Proyectos Piloto , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Advancements in therapies for Duchenne muscular dystrophy (DMD) have made diagnosis within the newborn period a high priority. We undertook a consortia approach to advance DMD newborn screening in the United States. This manuscript describes the formation of the Duchenne Newborn Screening Consortium, the development of the pilot protocols, data collection tools including parent surveys, and findings from the first year of a two-year pilot. The DMD pilot design is population-based recruitment of infants born in New York State. Data tools were developed to document the analytical and clinical validity of DMD NBS, capture parental attitudes, and collect longitudinal health information for diagnosed newborns. Data visualizations were updated monthly to inform the consortium on enrollment. After 12 months, 15,754 newborns were screened for DMD by the New York State Newborn Screening (NYS NBS) Program. One hundred and forty screened infants had borderline screening results, and sixteen infants were referred for molecular testing. Three male infants were diagnosed with dystrophinopathy. Data from the first year of a two-year NBS pilot for DMD demonstrate the feasibility of NBS for DMD. The consortia approach was found to be a useful model, and the Newborn Screening Translational Research Network's data tools played a key role in describing the NBS pilot findings and engaging stakeholders.
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Duchenne muscular dystrophy (DMD) is the most common pediatric-onset form of muscular dystrophy, occurring in 1 in 5,000 live male births. DMD is a multi-system disease resulting in muscle weakness with progressive deterioration of skeletal, heart, and smooth muscle, and learning disabilities. Pathogenic/likely pathogenic (P/LP) variants in the DMD gene, which encodes dystrophin protein, cause dystrophinopathy. All males with a P/LP variant in the X-linked DMD gene are expected to be affected. Two to 20% of female heterozygotes with a P/LP variant develop symptoms of dystrophinopathy ranging from mild muscle weakness to significant disability similar to Becker muscular dystrophy. Recently, with improvements in therapies and testing methodology, there is stronger evidence supporting newborn screening (NBS) for DMD for males and females because females may also develop symptoms. A consented pilot study to screen newborns for DMD was initiated in New York State (NYS) and conducted from 2019 to 2021. The identification of female carriers and the realization of the subsequent uncertainty of providers concerning follow-up during the pilot led to the development of algorithms for screening and diagnosis of carrier females, including both NBS and cascade molecular testing of family members.
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Distrofina , Distrofia Muscular de Duchenne , Niño , Masculino , Recién Nacido , Femenino , Humanos , Distrofina/genética , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Tamizaje Neonatal , Debilidad Muscular , Proyectos Piloto , AlgoritmosRESUMEN
Seven months after the launch of a pilot study to screen newborns for Duchenne Muscular Dystrophy (DMD) in New York State, New York City became an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. All in-person research activities were suspended at the study enrollment institutions of Northwell Health and NewYork-Presbyterian Hospitals, and study recruitment was transitioned to 100% remote. Pre-pandemic, all recruitment was in-person with research staff visiting the postpartum patients 1-2 days after delivery to obtain consent. With the onset of pandemic, the multilingual research staff shifted to calling new mothers while they were in the hospital or shortly after discharge, and consent was collected via emailed e-consent links. With return of study staff to the hospitals, a hybrid approach was implemented with in-person recruitment for babies delivered during the weekdays and remote recruitment for babies delivered on weekends and holidays, a cohort not recruited pre-pandemic. There was a drop in the proportion of eligible babies enrolled with the transition to fully remote recruitment from 64% to 38%. In addition, the proportion of babies enrolled after being approached dropped from 91% to 55%. With hybrid recruitment, the proportion of eligible babies enrolled (70%) and approached babies enrolled (84%) returned to pre-pandemic levels. Our experience adapting our study during the COVID-19 pandemic led us to develop new recruitment strategies that we continue to utilize. The lessons learned from this pilot study can serve to help other research studies adapt novel and effective recruitment methods.
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Identifying women at high risk for developing breast cancer is potentially lifesaving. Patients with pathogenic genetic variants can embark on a program of surveillance for early detection, chemoprevention, and/or prophylactic surgery. Newly diagnosed cancer patients can also use the results of gene panel sequencing to make decisions about surgery; therefore, rapid turnaround time for results is critical. Cancer Risk B (CR-B), a test that uses flow variant assays to assess the effects of variants in the DNA double-strand break repair, was applied to two groups of subjects who underwent coincidental gene panel testing, thereby allowing an assessment of sensitivity, specificity and accuracy, and utility for annotating variants of uncertain significance (VUS). The test was compared in matched peripheral blood mononuclear cells (PBMCs) and lymphoblastoid cells (LCLs) and tested for rescue in LCLs with gene transfer. The CR-B phenotype demonstrated a bimodal distribution: CR-B+ indicative of DSB repair defects, and CR-B-, indicative of wild-type repair. When comparing matched LCLs and PBMCs and inter-day tests, CR-B yielded highly reproducible results. The CR-B- phenotype was rescued by gene transfer using wild-type cDNA expression plasmids. The CR-B- phenotype predicted VUS as benign or likely benign. CR-B could represent a rapid alternative to panel sequencing for women with cancer and identifying women at high risk for cancer and is a useful adjunct for annotating VUS.
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During the COVID-19 pandemic, state newborn screening programs faced challenges to ensure this essential public health program continued to function at a high level. In December 2020, the EveryLife Foundation for Rare Diseases held a workshop to discuss these common challenges and solutions. Newborn screening officials described challenges including short staffing across the entire program, collection and transport of specimens, interrupted follow-up activities, and pilot study recruitment. To address these challenges, state programs implemented a wide variety of solutions to maintain the high standards of newborn screening. To address staffing issues, newborn screening programs, public health laboratories, and hospitals all cross-trained personnel, worked to manage staff stress, and established essential functions. Other solutions included working with courier companies to ensure the timely pick-up of specimen, creating educational materials for hospital staff, and the creation of hybrid recruitment models for pilot studies. Implementing the lessons discussed throughout this paper can help to prepare for the next public health emergencies to ensure that a program that interacts with millions of families every year and saves the lives of thousands of children every year is minimally impacted.
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Cardiac abnormalities such as left ventricular hypertrophy, left ventricular dilation, and pulmonary hypertension in sickle cell anemia have been previously described. Hydroxyurea, a disease-modifying therapy for sickle cell anemia, has been used for several decades. Longitudinal assessment of echocardiographic abnormalities in children and young adults with sickle cell anemia receiving hydroxyurea therapy is lacking. The goal of this retrospective study was to determine the prevalence of echocardiographic abnormalities in children and young adults with sickle cell anemia and to examine the effects of hydroxyurea on reverse cardiac remodeling. We reviewed the records of patients with sickle cell anemia who underwent routine cardiac screening at Cohen Children's Medical Center between 2010 and 2017, followed by retrospective longitudinal analysis of echocardiograms performed on patients receiving treatment with hydroxyurea. Data on a total of 100 patients with sickle cell anemia were analyzed; 60 (60%) were being treated with hydroxyurea. Twenty-five (41.6%) of the patients on hydroxyurea had been treated for <1 year; these patients had a significantly greater prevalence of left ventricular dilation compared with those who had been on treatment for >1 year. Serial echocardiograms of patients receiving hydroxyurea were then analyzed. Left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment. In addition, the left ventricular volume and mass correlated negatively with duration of treatment with hydroxyurea. Our study provides evidence that prolonged hydroxyurea therapy may lead to reverse cardiac remodeling. Future studies should attempt to follow up this patient cohort for a longer duration.
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Anemia de Células Falciformes , Hidroxiurea , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Niño , Estudios de Cohortes , Ecocardiografía , Humanos , Hidroxiurea/uso terapéutico , Estudios RetrospectivosRESUMEN
Although DNA methylation is the best characterized epigenetic mark, the mechanism by which it is targeted to specific regions in the genome remains unclear. Recent studies have revealed that local DNA methylation profiles might be dictated by cis-regulatory DNA sequences that mainly operate via DNA-binding factors. Consistent with this finding, we have recently shown that disruption of CTCF-binding sites by rare single nucleotide variants (SNVs) can underlie cis-linked DNA methylation changes in patients with congenital anomalies. These data raise the hypothesis that rare genetic variation at transcription factor binding sites (TFBSs) might contribute to local DNA methylation patterning. In this work, by combining blood genome-wide DNA methylation profiles, whole genome sequencing-derived SNVs from 247 unrelated individuals along with 133 predicted TFBS motifs derived from ENCODE ChIP-Seq data, we observed an association between the disruption of binding sites for multiple TFs by rare SNVs and extreme DNA methylation values at both local and, to a lesser extent, distant CpGs. While the majority of these changes affected only single CpGs, 24% were associated with multiple outlier CpGs within ±1kb of the disrupted TFBS. Interestingly, disruption of functionally constrained sites within TF motifs lead to larger DNA methylation changes at nearby CpG sites. Altogether, these findings suggest that rare SNVs at TFBS negatively influence TF-DNA binding, which can lead to an altered local DNA methylation profile. Furthermore, subsequent integration of DNA methylation and RNA-Seq profiles from cardiac tissues enabled us to observe an association between rare SNV-directed DNA methylation and outlier expression of nearby genes. In conclusion, our findings not only provide insights into the effect of rare genetic variation at TFBS on shaping local DNA methylation and its consequences on genome regulation, but also provide a rationale to incorporate DNA methylation data to interpret the functional role of rare variants.
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Islas de CpG/genética , Metilación de ADN , Epigénesis Genética , Genoma Humano/genética , Factores de Transcripción/metabolismo , Adolescente , Adulto , Sitios de Unión/genética , Niño , Preescolar , Secuenciación de Inmunoprecipitación de Cromatina , Estudios de Cohortes , Femenino , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/genética , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma , Adulto JovenAsunto(s)
Tejido Adiposo/patología , Cardiomiopatías/genética , Muerte Súbita Cardíaca/etiología , Ventrículos Cardíacos/patología , Mutación , Sarcoglicanopatías/genética , Sarcoglicanos/genética , Tabique Interventricular/patología , Tejido Adiposo/diagnóstico por imagen , Adulto , Cardiomiopatías/diagnóstico , Cardiomiopatías/fisiopatología , Femenino , Predisposición Genética a la Enfermedad , Ventrículos Cardíacos/diagnóstico por imagen , Herencia , Homocigoto , Humanos , Masculino , Linaje , Fenotipo , Sarcoglicanopatías/diagnóstico , Tabique Interventricular/diagnóstico por imagenRESUMEN
Cyanotic heart lesions are a complex subset of congenital heart disease (CHD) in which patients are desaturated until surgical repair or palliation. We hypothesized that a direct relationship would exist between degree of desaturation and presence of systemic inflammation and brain injury in unrepaired patients less than 1 year of age. The pre-operative desaturation with augmented systemic inflammation would predict a more complex post-operative course. Fifty patients with CHD were enrolled in this study and classified as cyanotic (O2 ≤ 90%) or acyanotic (O2 > 90%) based on SpO2. Serum inflammatory mediators measured included interleukins (IL)-6, IL-8, IL-12p70, IL-10, IL-1ß, tumor necrosis factor (TNF)-α, interferon (INF)-γ; macrophage inhibitory factor (MIF) and a novel brain biomarker, phosphorylated neurofilament heavy subunit (pNF-H). Twenty-two cyanotic and 28 acyanotic subjects were enrolled with SpO2 of 78 ± 18% and 98 ± 2% (p < 0.001), respectively, and mean age of 72 days (range 2-303) and 102 days (range 1-274), respectively. Cyanotic vs acyanotic subjects had elevated serum IL-6 (6.6 ± 7.6 vs 2.9 ± 2.9 pg/ml, p = 0.019) and pNF-H (222 ± 637 vs 57 ± 121 pg/ml, p = 0.046), and both biomarkers correlated with degree of desaturation (Spearman rank-order correlation ρ = - 0.30, p = 0.037 and ρ = - 0.29 p = 0.049, respectively). Post-operative inotrope scores at 24 h and duration of mechanical ventilation correlated inversely with pre-operative oxygen saturation (ρ = - 0.380, p = 0.014 and ρ = - 0.362, p = 0.020, respectively). The degree of pre-operative desaturation correlated with a more complicated post-operative course supporting the need for advanced peri-operative therapy in this population.
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Biomarcadores/sangre , Lesiones Encefálicas/sangre , Cianosis/sangre , Cardiopatías Congénitas/sangre , Lesiones Encefálicas/etiología , Cardiotónicos/administración & dosificación , Citocinas/sangre , Femenino , Cardiopatías Congénitas/complicaciones , Humanos , Lactante , Recién Nacido , Inflamación/sangre , Inflamación/complicaciones , Tiempo de Internación/estadística & datos numéricos , Masculino , Oxígeno/sangre , Periodo Posoperatorio , Estudios Prospectivos , Respiración Artificial/estadística & datos numéricosRESUMEN
OBJECTIVE: We aimed to correlate photoplethysmographic parameters with stroke volume in infants with PDA. Photoplethysmography constitutes the optical signal in pulse oximetry. STUDY DESIGN: Stroke volume was determined echocardiographically. Pulse transit time, right hand to foot arrival time difference, and relative amplitude were measured from pulse oximeter and ECG waveforms. Photoplethysmographic parameters before and after PDA closure were compared with stroke volume. RESULTS: After PDA closure, pulse transit time to the hand and to the foot were prolonged (54.7 ± 6.7 vs 65.5 ± 9.8 ms, p < 0.001, 82.5 ± 12.8 vs 88.6 ± 10.6 ms, p = 0.03), arrival time difference decreased (27.7 ± 7.6 vs 23.1 ± 5.6 ms, p = 0.021), and relative amplitude decreased (from 2.1 ± 0.7% to 1.5 ± 0.5%, p = 0.003). The time-based photoplethysmographic parameters correlated with stroke volume. CONCLUSIONS: Photoplethysmographic waveform parameters are significantly different before and after PDA closure and the time-based parameters correlate well with stroke volume. Monitoring pulse transit time may assist in evaluation for spontaneous PDA closure or response to therapy.
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Conducto Arterioso Permeable/fisiopatología , Pie/fisiología , Mano/fisiología , Fotopletismografía , Ecocardiografía , Femenino , Humanos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recien Nacido Extremadamente Prematuro , Recién Nacido , Masculino , Estudios Prospectivos , Análisis de la Onda del Pulso , Volumen SistólicoRESUMEN
OBJECTIVE: We hypothesize that routine daily transtelephonic monitoring (TTM) transmissions can accurately detect supraventricular tachycardia (SVT) in asymptomatic infants and/or assuage parental concerns rather than being used solely to diagnose arrhythmias. STUDY DESIGN: Single center, retrospective chart review of 60 patients with fetal or infant SVT prescribed TTM for at least 30 days, January 2010-September 2016. Patients were excluded if initial SVT was not documented, was perioperative, was atrial flutter/fibrillation, or chaotic atrial tachycardia. Categorical variables expressed as mean ± SD. Mann-Whitney, Spearman correlation, and Fisher exact tests were used for continuous and categorical variables respectively. RESULTS: Sixty patients were included. There were 2688 TTM transmissions received from 55 of 60 patients over 61.1 ± 66.7 days (0.73 ± 0.65 TTM/patient/days). Routine asymptomatic TTM transmissions revealed actionable findings in 5 of 2801 TTM transmissions sent by 5 patients (8.3%). No patient presented in shock or died. Forty-five of 2688 TTM transmissions were sent for parental concerns/symptoms in 16 patients (25.8%) with findings of normal sinus rhythm in 37 of 45 TTM transmissions and SVT in 8 of 45 TTM transmissions. Symptomatic actionable findings were more likely sent by patients discharged on class I or III antiarrhythmics (95% CI = 11.5%-68.3%, P = .004) and patients with prolonged initial hospitalizations (95% CI = 6.98%-59.7%, P = .01). Flecainide was discontinued in 1 patient after widened QRS was noted on routine TTM. CONCLUSIONS: TTM accurately diagnose asymptomatic recurrent SVT in neonates and infants before they develop signs of congestive heart failure or shock and is helpful for recurrent SVT management.
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Taquicardia Supraventricular/diagnóstico , Telemetría/métodos , Antiarrítmicos/uso terapéutico , Electrocardiografía , Femenino , Humanos , Lactante , Recién Nacido , Tiempo de Internación/estadística & datos numéricos , Masculino , Estudios Retrospectivos , Taquicardia Supraventricular/tratamiento farmacológico , Telemetría/estadística & datos numéricos , TeléfonoRESUMEN
The potential role of systemic inflammation on brain injury in newborns with congenital heart disease (CHD) was assessed by measuring levels of central nervous system (CNS)-derived proteins in serum prior to and following cardiac surgery. A total of 23 newborns (gestational age, 39±1 weeks) with a diagnosis of CHD that required cardiac surgery with cardiopulmonary bypass (CPB) were enrolled in the current study. Serum samples were collected immediately prior to surgery and 2, 24 and 48 h following CPB, and serum levels of phosphorylated neurofilament-heavy subunit (pNF-H), neuron-specific enolase (NSE) and S100B were analyzed. Systemic inflammation was assessed by measuring serum concentrations of complement C5a and complement sC5b9, and the following cytokines: Interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL12p70, interferon γ and tumor necrosis factor (TNF)-α. Analysis of cord blood from normal term deliveries (n=26) provided surrogate normative values for newborns. pNF-H and S100B were 2.4- to 2.8-fold higher (P<0.0001) in patient sera than in cord blood prior to surgery and remained elevated following CPB. Pre-surgical serum pNF-H and S100B levels directly correlated with interleukin (IL)-12p70 (ρ=0.442, P<0.05). pNF-H was inversely correlated with arterial pO2 prior to surgery (ρ=-0.493, P=0.01) and directly correlated with arterial pCO2 post-CPB (ρ=0.426, P<0.05), suggesting that tissue hypoxia and inflammation contribute to blood brain barrier (BBB) dysfunction and neuronal injury. Serum IL12p70, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher in patients than in normal cord blood and levels of these cytokines increased following CPB (P<0.001). Activation of complement was observed in all patients prior to surgery, and serum C5a and sC5b9 remained elevated up to 48 h post-surgery. Furthermore, they were correlated (P<0.05) with low arterial pO2, high pCO2 and elevated arterial pressure in the postoperative period. Length of mechanical ventilation was associated directly with post-surgery serum IL-12p70 and IL-8 concentrations (P<0.05). Elevated serum concentrations of pNF-H and S100B in neonates with CHD suggest BBB dysfunction and CNS injury, with concurrent hypoxemia and an activated inflammatory response potentiating this effect.
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Infants of diabetic mothers (IDMs) with hypertrophic cardiomyopathy are recognized to have impaired myocardial performance, but less is known about ventricular function in IDMs without hypertrophy. We hypothesized that in asymptomatic newborns with normal two-dimensional echocardiographic evaluations, pulsed wave tissue Doppler imaging (TDI) would suggest a subclinical decrease in the cardiac function of IDMs compared to infants of non-diabetics (nIDMs). This is a retrospective cohort study of asymptomatic neonates ≥36 weeks gestation, at 0-7 days of life, with normal standard echocardiograms. Systolic (S'), early diastolic (E'), and late diastolic (A') TDI velocities were measured at the mitral valve (MV) annulus, basal interventricular septum (IVS), and tricuspid valve (TV) annulus, and averaged from three consecutive cardiac cycles. Demographic, perinatal, and echocardiographic variables were compared between IDM and nIDM groups. Of 631 subjects, 75 IDMs were identified. The mean gestational age of the entire cohort was 39.33 weeks (±1.26), birth weight 3.44 kg (±0.56), and body surface area (BSA) 0.21 m2 (±0.02). IDMs had significantly greater birth weight and BSA, lower gestational age, older maternal age, and higher incidence of maternal obesity and hypertension than nIDMs (p < 0.001). On multivariable analysis, IDMs had significantly lower S' (p ≤ 0.03) and E' (p < 0.001) velocities, and higher E/E' ratios (p < 0.001) at the MV, IVS, and TV than nIDMs. In asymptomatic newborn IDMs without cardiac hypertrophy, pulsed wave TDI suggests a subclinical decrease in systolic and diastolic myocardial function compared to nIDMs.
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Ecocardiografía Doppler de Pulso , Corazón/fisiopatología , Embarazo en Diabéticas/fisiopatología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Adulto , Complicaciones de la Diabetes/complicaciones , Complicaciones de la Diabetes/fisiopatología , Femenino , Corazón/diagnóstico por imagen , Humanos , Recién Nacido , Masculino , Miocardio , Embarazo , Estudios Retrospectivos , Disfunción Ventricular Izquierda/etiologíaRESUMEN
Pulmonary regurgitation and/or stenosis (PS) is challenging in patients with congenital heart defects. Our aim was to identify if criteria for referral were different between surgical (SPVR) and transcatheter pulmonary valve replacement (TPVR) populations, and to further assess if any baseline differences influence the resultant ventricular remodeling at medium-term follow-up. Retrospective chart review of patients post-SPVR or TPVR at our center from 2013 to 2015 was conducted. Volumetric data from cardiac magnetic resonance (CMR), 1 year before and 1 year after PVR was obtained. PS was defined as peak-peak gradient ≥35 mmHg by catheterization or peak gradient ≥50 mmHg by echocardiography. Thirty patients underwent PVR: 15 SPVR and 15 TPVR (1 hybrid). The indications for SPVR referral were: 2+ CMR parameters in 80% of patients; decreased left ventricular ejection fraction and hemodynamic findings and/or abnormal exercise stress test in 20%. The indications for TPVR referral were predominantly symptoms ± hemodynamic findings in 66% of patients, 2+ CMR findings in 44% of patients. At referral, SPVR group had significantly larger right ventricular (RV) volumes than TPVR group. Biventricular function was not significantly different. Post-PVR, both groups had significantly decreased RV volumes and increased LV diastolic volumes. The SPVR group improved LV cardiac output and biventricular function whereas TPVR group had no significant improvement. The patients in the SPVR group were mostly referred based on CMR volumetric criteria, whereas the patients in the TPVR group were mostly referred due to exercise intolerance with only occasional abnormalities on CMR. 1 year after PVR, both groups had near-normal biventricular volumes and function irrespective of characteristics at referral.
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Procedimientos Quirúrgicos Cardíacos/métodos , Cardiopatías Congénitas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Insuficiencia de la Válvula Pulmonar/cirugía , Válvula Pulmonar/cirugía , Función Ventricular , Adolescente , Adulto , Ecocardiografía , Femenino , Cardiopatías Congénitas/complicaciones , Ventrículos Cardíacos/diagnóstico por imagen , Hemodinámica , Humanos , Masculino , Estudios Retrospectivos , Volumen Sistólico , Resultado del Tratamiento , Adulto JovenRESUMEN
Transthoracic echocardiography is the most common noninvasive method of evaluating pulmonary hypertension (PH) in infants. Identification of reliable, quantitative indices of myocardial function may enhance the diagnostic value of echocardiography in this population. We hypothesized that pulsed wave tissue Doppler imaging (TDI) and tricuspid annular plane systolic excursion (TAPSE) would be reproducible measurements and would suggest decreased ventricular function, in infants with PH. This retrospective case-control study involved subjects diagnosed clinically and echocardiographically with PH at <12 months of age, matched with controls by age and gestational age (GA). TAPSE was measured by M-mode in the apical 4-chamber view. TDI velocities were averaged from three consecutive cardiac cycles. Observers were blinded to patient identity and clinical status. Fifty-seven subjects, including 35 term or near-term infants ≥35 weeks GA [mean GA 39 weeks (±1.7), median age 1 day (range 0-2)] and 22 preterm infants [median GA 25.4 weeks (24.1-26.6), age 66 days (4-128)], were matched with 57 controls. Subjects with PH had lower TAPSE (term p < 0.001, preterm p = 0.03) and TAPSE indexed to body surface area (term p < 0.001, preterm p = 0.005). Mitral annular, septal, and tricuspid annular systolic (S') and early diastolic (E') TDI velocities were also decreased compared to controls (all p < 0.05). Intraclass correlation demonstrated 84-99% agreement between observers in measuring TDI and 92% for TAPSE. Intraobserver reliability for these measures was 98-99% and 96%, respectively. We concluded that TDI and TAPSE are reproducible indices of myocardial function and may serve as useful adjuncts to standard echocardiographic measures in infants with PH.