Evaluation of Regional Myocardial Work Indices in Pediatric Essential and Renal or Renovascular Hypertension.

BACKGROUND: Myocardial work (MW) is an index of LV function based on pressure-strain loops and brachial cuff pressure measurement. MW has been proposed as more sensitive than conventional functional parameters, as it accounts for afterload and myocardial deformation. However, many studies have been limited to assessment of global MW indices, neglecting regional differences in cardiac associated with hypertension and consequent cardiac remodeling. We aimed to quantify regional MW in pediatric hypertension and compare the findings in renal or renovascular hypertension (RHTN) with essential hypertension (EHTN). METHODS: We retrospectively assessed conventional markers of LV function, and both global and regional MW indices in 78 patients (49 males, 15.4 ± 2.94 years) with EHTN and RHTN. RESULTS: Peak systolic strain (PSS) in the basal septal segment was significantly impaired in patients with RHTN compared to EHTN (-13.00% [-15.50%; -13.00%] vs. -15.00% [-17.50%; -13.50%], P = 0.034). Similarly, basal septal MW indices were significantly elevated in patients with EHTN compared to RHTN, including MW efficiency (MWE) (95.0% [93.0%; 98.0%] vs. 94.0% [89.0%; 95.0%], P = 0.004) and constructive work (CW) (1700 mm Hg% (409 mm Hg%) vs. 1520 mm Hg% (336 mm Hg%), P = 0.037). Wasted work (WW) was significantly elevated in the RHTN group (79.0 mm Hg% [28.5 mm Hg%; 104 mm Hg%] vs. 105 mm Hg% [62.0 mm Hg%; 164 mm Hg%], P = 0.010). CONCLUSION: Significant differences in basal septal PSS and MW indices were observed between EHTN and RHTN. These findings highlight the usefulness of regional MW indices in assessing disease and may help differentiate between etiologies of pediatric hypertension.

Native T1 mapping detects both acute clinical rejection and graft dysfunction in pediatric heart transplant patients.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is emerging as an important tool for cardiac allograft assessment. Native T1 mapping may add value in identifying rejection and in assessing graft dysfunction and myocardial fibrosis burden. We hypothesized that CMR native T1 values and features of textural analysis of T1 maps would identify acute rejection, and in a secondary analysis, correlate with markers of graft dysfunction, and with fibrosis percentage from endomyocardial biopsy (EMB). METHODS: Fifty cases with simultaneous EMB, right heart catheterization, and 1.5 T CMR with breath-held T1 mapping via modified Look-Locker inversion recovery (MOLLI) in 8 short-axis slices and subsequent quantification of mean and peak native T1 values, were performed on 24 pediatric subjects. A single mid-ventricular slice was used for image texture analysis using nine gray-level co-occurrence matrix features. Digital quantification of Masson trichrome stained EMB samples established degree of fibrosis. Markers of graft dysfunction, including serum brain natriuretic peptide levels and hemodynamic measurements from echocardiography, catheterization, and CMR were collated. Subjects were divided into three groups based on degree of rejection: acute rejection requiring new therapy, mild rejection requiring increased ongoing therapy, and no rejection with no change in treatment. Statistical analysis included student's t-test and linear regression. RESULTS: Peak and mean T1 values were significantly associated with acute rejection, with a monotonic trend observed with increased grade of rejection. Texture analysis demonstrated greater spatial heterogeneity in T1 values, as demonstrated by energy, entropy, and variance, in cases requiring treatment. Interestingly, 2 subjects who required increased therapy despite low grade EMB results had abnormal peak T1 values. Peak T1 values also correlated with increased BNP, right-sided filling pressures, and capillary wedge pressures. There was no difference in histopathological fibrosis percentage among the 3 groups; histopathological fibrosis did not correlate with T1 values or markers of graft dysfunction. CONCLUSION: In pediatric heart transplant patients, native T1 values identify acute rejection requiring treatment and may identify graft dysfunction. CMR shows promise as an important tool for evaluation of cardiac grafts in children, with T1 imaging outperforming biopsy findings in the assessment of rejection.

Real-Time Prediction of Mortality, Cardiac Arrest, and Thromboembolic Complications in Hospitalized Patients With COVID-19.

Background: COVID-19 infection carries significant morbidity and mortality. Current risk prediction for complications in COVID-19 is limited, and existing approaches fail to account for the dynamic course of the disease. Objectives: The purpose of this study was to develop and validate the COVID-HEART predictor, a novel continuously updating risk-prediction technology to forecast adverse events in hospitalized patients with COVID-19. Methods: Retrospective registry data from patients with severe acute respiratory syndrome coronavirus 2 infection admitted to 5 hospitals were used to train COVID-HEART to predict all-cause mortality/cardiac arrest (AM/CA) and imaging-confirmed thromboembolic events (TEs) (n = 2,550 and n = 1,854, respectively). To assess COVID-HEART's performance in the face of rapidly changing clinical treatment guidelines, an additional 1,100 and 796 patients, admitted after the completion of development data collection, were used for testing. Leave-hospital-out validation was performed. Results: Over 20 iterations of temporally divided testing, the mean area under the receiver operating characteristic curve were 0.917 (95% confidence interval [CI]: 0.916-0.919) and 0.757 (95% CI: 0.751-0.763) for prediction of AM/CA and TE, respectively. The interquartile ranges of median early warning times were 14 to 21 hours for AM/CA and 12 to 60 hours for TE. The mean area under the receiver operating characteristic curve for the left-out hospitals were 0.956 (95% CI: 0.936-0.976) and 0.781 (95% CI: 0.642-0.919) for prediction of AM/CA and TE, respectively. Conclusions: The continuously updating, fully interpretable COVID-HEART predictor accurately predicts AM/CA and TE within multiple time windows in hospitalized COVID-19 patients. In its current implementation, the predictor can facilitate practical, meaningful changes in patient triage and resource allocation by providing real-time risk scores for these outcomes. The potential utility of the predictor extends to COVID-19 patients after hospitalization and beyond COVID-19.

Epiblepharon in a Case of Anterior Megalophthalmos: A Diagnostic Red Herring.

Epiblepharon is a condition characterized by the presence of a congenital horizontal fold of skin near the upper or lower eyelid margin and rarely requires intervention. In this communication, we present the case of a five-month-old child who had enlarged eyes, tearing, and intense photophobia; and was referred to as a case of congenital glaucoma. Congenital or infantile glaucoma can, indeed present with enlarged eyes, watering, and photophobia. However, in the absence of optic disc cupping and elevated intraocular pressures, a diagnosis of anterior megalophthalmos should be considered, especially in the presence of a very deep anterior chamber. Subsequent evaluation in our case established the diagnosis of anterior megalophthalmos along with concomitant bilateral epiblepharon. The child underwent surgery to correct the epiblepharon, following which, the tearing and photophobia resolved. The clinical characteristics of anterior megalophthalmos and the causality between an enlarged globe and epiblepharon are discussed in this article.

Predictors and ocular outcomes of rescue treatment in preterm infants with treated retinopathy of prematurity-a retrospective study.

AIM: To determine predictors of rescue treatment among infants treated for retinopathy of prematurity and to evaluate their ocular outcomes at 18-24 months of corrected age. METHODS: This is a single centre retrospective study of infants who received treatment for type 1 ROP, using laser photocoagulation or anti VEGF agents. Multivariable logistic regression was used to generate a prediction model for rescue treatment of ROP. The primary outcome was an abnormal refractive outcome by 24 months of corrected age, among infants primarily treated with laser therapy. RESULTS: Two hundred and eight infants (including 416 eyes) who received single (n = 151) or rescue (multiple) treatments (n = 57) were included. Ninety three percent of the infants were primarily treated with laser photocoagulation. Lower gestational age, small for gestational age, early packed red blood cell transfusion (within 2 weeks of postnatal age), and presence of Zone 1 retinopathy predicted the need for rescue treatment in treated infants [area under the receiver operating characteristic curve: 0.81 (0.73-0.89)]. The incidence of abnormal refractive outcome, assessed in a total of 174 infants, was found to be significantly higher in the rescue treatment group (67% versus 21%, adjusted odds ratio: 7.56 (3.3-17.2), P < 0.001). Myopia, very high myopia and use of spectacles was significantly higher in the rescue treatment group (P < 0.001 for each). CONCLUSIONS: Rescue treatment for ROP was associated with an increased incidence of refractive errors and requirement of spectacles by 2 years of age. Larger prospective multicentre studies are required to confirm the findings from our study.

Quantitative cardiac magnetic resonance T2 imaging offers ability to non-invasively predict acute allograft rejection in children.

BACKGROUND: Monitoring for acute allograft rejection improves outcomes after cardiac transplantation. Endomyocardial biopsy is the gold standard test defining rejection, but carries risk and has limitations. Cardiac magnetic resonance T2 mapping may be able to predict rejection in adults, but has not been studied in children. Our aim was to evaluate T2 mapping in identifying paediatric cardiac transplant patients with acute rejection. METHODS: Eleven paediatric transplant patients presenting 18 times were prospectively enrolled for non-contrast cardiac magnetic resonance at 1.5 T followed by endomyocardial biopsy. Imaging included volumetry, flow, and T2 mapping. Regions of interest were manually selected on the T2 maps using the middle-third technique in the left ventricular septal and lateral wall in a short-axis and four-chamber slice. Mean and maximum T2 values were compared with Student's t-tests analysis. RESULTS: Five cases of acute rejection were identified in three patients, including two cases of grade 2R on biopsy and three cases of negative biopsy treated for clinical symptoms attributed to rejection (new arrhythmia, decreased exercise capacity). A monotonic trend between increasing T2 values and higher biopsy grades was observed: grade 0R T2 53.4 ± 3 ms, grade 1R T2 54.5 ms ± 3 ms, grade 2R T2 61.3 ± 1 ms. The five rejection cases had significantly higher mean T2 values compared to cases without rejection (58.3 ± 4 ms versus 53 ± 2 ms, p = 0.001). CONCLUSIONS: Cardiac magnetic resonance with quantitative T2 mapping may offer a non-invasive method for screening paediatric cardiac transplant patients for acute allograft rejection. More data are needed to understand the relationship between T2 and rejection in children.

Intranasal fentanyl for pain management during screening for retinopathy of prematurity in preterm infants: a randomized controlled trial.

OBJECTIVE: To study the efficacy of intranasal fentanyl as an adjunct for pain management during screening for retinopathy of prematurity (ROP) in preterm infants. STUDY DESIGN: In this single center, double blinded, randomized controlled trial, preterm neonates between 30 and 34 weeks postmenstrual age received either intranasal fentanyl (2 mcg/kg) or intranasal normal saline through a mucosal atomization device 5 min prior to the first ROP-screening examination. Both the groups received standard pain relief strategies (oral sucrose, 0.5% proparacaine eye drops and physical containment). The primary outcome was premature infant pain profile-revised (PIPP-R) score during the screening. RESULTS: A total of 111 infants were enrolled. PIPP-R score during the retinal examination was significantly lower in the fentanyl group (8.3 versus 11.5, mean difference: 3.2 (2.46-4.06), P < 0.001). There was no significant difference in the incidence of adverse effects. CONCLUSION: Intranasal fentanyl significantly reduced the pain associated with retinal examination without increasing the risk of respiratory depression. Large RCTs are required to verify the efficacy and safety of intranasal fentanyl for acute procedural pain in neonates. CLINICAL TRIAL REGISTRATION: CTRI/2017/12/011016.

How personalized heart modeling can help treatment of lethal arrhythmias: A focus on ventricular tachycardia ablation strategies in post-infarction patients.

Precision Cardiology is a targeted strategy for cardiovascular disease prevention and treatment that accounts for individual variability. Computational heart modeling is one of the novel approaches that have been developed under the umbrella of Precision Cardiology. Personalized computational modeling of patient hearts has made strides in the development of models that incorporate the individual geometry and structure of the heart as well as other patient-specific information. Of these developments, one of the potentially most impactful is the research aimed at noninvasively predicting the targets of ablation of lethal arrhythmia, ventricular tachycardia (VT), using patient-specific models. The approach has been successfully applied to patients with ischemic cardiomyopathy in proof-of-concept studies. The goal of this paper is to review the strategies for computational VT ablation guidance in ischemic cardiomyopathy patients, from model developments to the intricacies of the actual clinical application. To provide context in describing the road these computational modeling applications have undertaken, we first review the state of the art in VT ablation in the clinic, emphasizing the benefits that personalized computational prediction of ablation targets could bring to the clinical electrophysiology practice. This article is characterized under: Analytical and Computational Methods > Computational Methods Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models Translational, Genomic, and Systems Medicine > Translational Medicine.

Ventricular arrhythmia risk prediction in repaired Tetralogy of Fallot using personalized computational cardiac models.

BACKGROUND: Adults with repaired tetralogy of Fallot (rTOF) are at increased risk for ventricular tachycardia (VT) due to fibrotic remodeling of the myocardium. However, the current clinical guidelines for VT risk stratification and subsequent implantable cardioverter-defibrillator deployment for primary prevention of sudden cardiac death in rTOF remain inadequate. OBJECTIVE: The purpose of this study was to determine the feasibility of using an rTOF-specific virtual-heart approach to identify patients stratified incorrectly as being at low VT risk by current clinical criteria. METHODS: This multicenter retrospective pilot study included 7 adult rTOF patients who were considered low risk for VT based on clinical criteria. Patient-specific computational heart models were generated from late gadolinium enhanced magnetic resonance imaging (LGE-MRI), incorporating the individual distribution of rTOF fibrotic remodeling in both ventricles. Simulations of rapid pacing determined VT inducibility. Model creation and simulations were performed by operators blinded to clinical outcome. RESULTS: Two patients in the study experienced clinical VT. The virtual hearts constructed from LGE-MRI scans of 7 rTOF patients correctly predicted reentrant VT in the models from VT-positive patients and no arrhythmia in those from VT-negative patients. There were no statistically significant differences in clinical criteria commonly used to assess VT risk, including QRS duration and age, between patients who did and those who did not experience clinical VT. CONCLUSION: This study demonstrates the feasibility of image-based virtual-heart modeling in patients with congenital heart disease and structurally abnormal hearts. It highlights the potential of the methodology to improve VT risk stratification in patients with rTOF.

Surgical management of Helveston syndrome (triad of A- pattern exotropia, superior oblique overaction and dissociated vertical deviation) using 'Four Oblique' procedure.

Purpose: To report the surgical outcomes in six patients of Helveston syndrome using a "four oblique" procedure. The popular methods for surgical management include superior rectus recessions alone or combined with superior oblique tenectomy. However, large angle exotropia correction would entail a higher risk of anterior segment ischemia when the superior rectus needs to be operated along with the horizontal recti. Hence, we evaluated the long-term results of this uncommon procedure. Methods: This was a retrospective review of six patients diagnosed to have manifest dissociated vertical deviation (DVD) with A pattern exotropia with bilateral superior oblique over action. All patients underwent horizontal muscle recessions/resections for exotropia along with bilateral posterior tenectomy of the superior oblique with inferior oblique anterior transpositioning. Results: The median age was 10 years (Range 5-26 years). The mean postoperative follow-up was 26 ± 14.02 months (Range 12-48 months). The mean reduction in exotropia was from 36.5 ± 21.06 PD (Range 15-65 PD) to 6.1 ± 3.06 PD (Range 3-10 PD). The procedure corrected the A pattern from a mean 23 ± 7 PD (Range 15-35 PD) to 7.6 ± 3.2 PD (Range 3-10 PD). The average DVD in the right eye reduced from 14 ± 4.3 PD (Range 8-20 PD) to 5.3 ± 1.2 PD and in the left eye from 14.33 ± 3.6 PD (Range 10-18 PD) to 4.1 ± 1.1 PD. The DVD asymmetry reduced from 6.33 ± 3.4 PD to 1.5 ± 1.3 PD. Conclusion: "Four oblique" procedure with horizontal muscle surgery seems to be an effective method for significantly correcting the A pattern as well as reducing the DVD with good long-term outcome in our case series.

Linezolid induced optic neuropathy in a child treated for extensively drug resistant tuberculosis: A case report and review of literature.

Linezolid induced optic neuropathy occurring after prolonged use of the drug is rarely reported in the paediatric age group. We report a case of Linezolid induced optic neuropathy in a child treated for extensively drug resistant tuberculosis. The optic neuropathy completely reversed with good improvement in vision after stopping the drug, which to the best of our knowledge has not been reported before.

Feasibility of Non-invasive Fetal Electrocardiographic Interval Measurement in the Outpatient Clinical Setting.

Non-invasive fetal electrocardiography (ECG) is a promising method for evaluating fetal cardiac electrical activity. Despite advances in fetal ECG technology, its ability to provide reliable, interpretable results in a typical outpatient fetal cardiology setting remains unclear. We sought to determine the feasibility of measuring standard ECG intervals in an outpatient fetal cardiology practice using an abdominal fetal ECG device that employs blind source separation with reference, an innovative signal-processing technique for fetal ECG extraction. Women scheduled for clinically indicated outpatient fetal echocardiogram underwent 10 min of fetal ECG acquisition from the maternal abdomen using specialized gel electrodes. A bedside laptop computer performed fetal ECG extraction, allowing real-time visualization of fetal and maternal ECG signals. Offline post-processing of 1 min of recorded data yielded fetal P-wave duration, PR interval, QRS duration, RR interval, QT interval, and QTc. Fifty-five fetuses were studied with gestational age 18-37 weeks, including 13 with abnormal fetal echocardiogram findings and three sets of twins. Interpretable results were obtained in 91% of fetuses, including 85% during the vernix period and 100% of twin fetuses. PR interval and RR interval of 18-24 week gestation fetuses were significantly shorter than those with gestational age 25-31 and 32-37 weeks. Of the six fetuses with abnormal rhythms on fetal echocardiogram, fetal ECG tracing was interpretable in five and matched the rhythm noted on fetal echocardiogram. Abdominal fetal ECG acquisition is feasible for arrhythmia detection and ECG interval calculation in a routine clinical setting.

Feasibility of a semi-automated method for cardiac conduction velocity analysis of high-resolution activation maps.

Myocardial conduction velocity is important for the genesis of arrhythmias. In the normal heart, conduction is primarily dependent on fiber direction (anisotropy) and may be discontinuous at sites with tissue heterogeneities (trabeculated or fibrotic tissue). We present a semi-automated method for the accurate measurement of conduction velocity based on high-resolution activation mapping following central stimulation. The method was applied to activation maps created from myocardium from man, sheep and mouse with anisotropic and discontinuous conduction. Advantages of the presented method over existing methods are discussed.

Effect of resistive barrier location on the relationship between T-wave alternans and cellular repolarization alternans: a 1-D modeling study.

Structural inhomogeneities in cardiac tissue have been associated with increased cellular repolarization alternans in animal experiments and increased T-wave alternans (TWA) in clinical studies. However, the effect of structural inhomogeneities on the relationship between cellular alternans and TWA has not been thoroughly investigated. We created 1-dimensional multicellular fiber models with and without a resistive barrier in various fiber regions and paced each model to induce cellular alternans. The models demonstrate that a resistive barrier in one fiber region substantially alters cellular repolarization alternans throughout the fiber. A midmyocardial or subepicardial barrier increase both TWA amplitude and maximum cellular alternans magnitude, relative to a fiber without a barrier. In addition, a direct relationship exists between TWA amplitude and maximum cellular alternans magnitude, which was highly dependent on barrier location. These results suggest that the position of a structural inhomogeneity within the myocardium may have substantial effects on dynamic repolarization instability and arrhythmogenicity.