Prenatal Detection of Congenital Heart Disease: Importance of Fetal Echocardiography Following Normal Fetal Cardiac Screening.

Fetal echocardiography may be performed because of noncardiac indications (the pregnancy is identified as high risk for fetal cardiac disease), or because of fetal cardiac indications (abnormal fetal heart at the time of a screening ultrasound). Considering recent improvements in fetal cardiac screening over the past decade, the goal of this single institution study was to reconsider the importance of performing fetal echocardiography purely for screening (noncardiac) indications. We performed a retrospective analysis to review screening and fetal cardiac indications and fetal cardiac findings for fetal echocardiograms performed at UCLA between 2015 and 2019. Fetal heart disease was identified in 391 (15%) of 2592 pregnancies in this study. Among these 391 cases, 227 (58%) occurred in low-risk pregnancies (without screening indications). While 79% of the cases of fetal cardiac disease were referred with fetal cardiac indications, 21% of the cases were referred with exclusively screening indications. Fetal cardiac disease was discovered on fetal echocardiograms in 4% of pregnancies referred for exclusively screening indications, but the frequency of fetal cardiac disease following normal fetal cardiac screening has decreased from 6% in 2015 to 3% in 2019. In our population, we recommend continued referral for fetal echocardiography for pregnancies identified as high risk for CHD. However, as fetal cardiac screening continues to improve, referral for fetal echocardiography following normal fetal cardiac screening will have diminishing value and yield.

Major aortopulmonary collateral arteries in association with atrioventricular septal defect with balanced ventricles and trisomy 21.

A major aortopulmonary collateral artery is a rare and easily missed diagnosis that is usually associated with Tetralogy of Fallot or pulmonary atresia. We present two cases of major aortopulmonary collaterals associated with trisomy 21 and atrioventricular septal defect with balanced ventricles in which the diagnosis went undetected until after initial cardiac repair.

A comparison of relative survival and cause-specific survival methods to measure net survival in cancer populations.

BACKGROUND: Accurate cancer survival statistics are necessary for describing population-level survival patterns and measuring advancements in cancer care. Net cancer survival is measured using two methods: cause-specific survival (CSS) and relative survival (RS). Both are valid methodologies for estimating net survival and are used widely in medical research. In these analyses, we compare CSS to RS at selected cancer sites. METHODS: Using data from 18 SEER registries between 2000 and 2014, five-year RS and CSS estimates were generated overall as well as by age groups and by sex. To assess how closely the two survival methods corresponded, net survival percent difference was calculated with the following formula: ((RS-CSS)/RS)*100. RESULTS: Discrepancies between estimates obtained from CSS and RS methods varied with cancer site and age, but not by sex. In most cases, CSS was greater than RS, but cancers with available early screening and high survival rate had higher RS than CSS. Net survival percent differences were small in children and adolescents and young adults, and large in adults over the age of 40. CONCLUSIONS: While both CSS and RS aim to quantify net survival, the estimates tend to differ due to the biases present in both methodologies. Error when estimating CSS most frequently stems from misclassification of cause of death, whereas RS is subject to error when no suitable life tables are available. Appropriate use of CSS and RS requires a detailed understanding of the characteristics of the disease that may lead to differences in the estimates generated by these methods.

Exosomal MicroRNA Transfer Into Macrophages Mediates Cellular Postconditioning.

BACKGROUND: Cardiosphere-derived cells (CDCs) confer cardioprotection in acute myocardial infarction by distinctive macrophage (Mϕ) polarization. Here we demonstrate that CDC-secreted exosomes (CDCexo) recapitulate the cardioprotective effects of CDC therapy known as cellular postconditioning. METHODS: Rats and pigs underwent myocardial infarction induced by ischemia/reperfusion before intracoronary infusion of CDCexo, inert fibroblast exosomes (Fbexo; control), or vehicle. Two days later, infarct size was quantified. Macrophages were isolated from cardiac tissue or bone marrow for downstream analyses. RNA sequencing was used to determine exosome content and alterations in gene expression profiles in Mϕ. RESULTS: Administration of CDCexo but not Fbexo after reperfusion reduces infarct size in rat and pig models of myocardial infarction. Furthermore, CDCexo reduce the number of CD68+ Mϕ within infarcted tissue and modify the polarization state of Mϕ so as to mimic that induced by CDCs. CDCexo are enriched in several miRNAs (including miR-146a, miR-181b, and miR-126) relative to Fbexo. Reverse pathway analysis of whole-transcriptome data from CDCexo-primed Mϕ implicated miR-181b as a significant (P=1.3x10-21) candidate mediator of CDC-induced Mϕ polarization, and PKCδ (protein kinase C δ) as a downstream target. Otherwise inert Fbexo loaded selectively with miR-181b alter Mϕ phenotype and confer cardioprotective efficacy in a rat model of myocardial infarction. Adoptive transfer of PKCδ-suppressed Mϕ recapitulates cardioprotection. CONCLUSIONS: Our data support the hypothesis that exosomal transfer of miR-181b from CDCs into Mϕ reduces PKCδ transcript levels and underlies the cardioprotective effects of CDCs administered after reperfusion.

Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction.

Ischemic injury in the heart induces an inflammatory cascade that both repairs damage and exacerbates scar tissue formation. Cardiosphere-derived cells (CDCs) are a stem-like population that is derived ex vivo from cardiac biopsies; they confer both cardioprotection and regeneration in acute myocardial infarction (MI). While the regenerative effects of CDCs in chronic settings have been studied extensively, little is known about how CDCs confer the cardioprotective process known as cellular postconditioning. Here, we used an in vivo rat model of ischemia/reperfusion (IR) injury-induced MI and in vitro coculture assays to investigate how CDCs protect stressed cardiomyocytes. Compared with control animals, animals that received CDCs 20 minutes after IR had reduced infarct size when measured at 48 hours. CDCs modified the myocardial leukocyte population after ischemic injury. Specifically, introduction of CDCs reduced the number of CD68+ macrophages, and these CDCs secreted factors that polarized macrophages toward a distinctive cardioprotective phenotype that was not M1 or M2. Systemic depletion of macrophages with clodronate abolished CDC-mediated cardioprotection. Using both in vitro coculture assays and a rat model of adoptive transfer after IR, we determined that CDC-conditioned macrophages attenuated cardiomyocyte apoptosis and reduced infarct size, thereby recapitulating the beneficial effects of CDC therapy. Together, our data indicate that CDCs limit acute injury by polarizing an effector macrophage population within the heart.

Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium.

Vagal nerve stimulation (VNS) has been proposed as a cardioprotective intervention. However, regional ventricular electrophysiological effects of VNS are not well characterized. The purpose of this study was to evaluate effects of right and left VNS on electrophysiological properties of the ventricles and hemodynamic parameters. In Yorkshire pigs, a 56-electrode sock was used for epicardial (n = 12) activation recovery interval (ARI) recordings and a 64-electrode catheter for endocardial (n = 9) ARI recordings at baseline and during VNS. Hemodynamic recordings were obtained using a conductance catheter. Right and left VNS decreased heart rate (84 ± 5 to 71 ± 5 beats/min and 84 ± 4 to 73 ± 5 beats/min), left ventricular pressure (89 ± 9 to 77 ± 9 mmHg and 91 ± 9 to 83 ± 9 mmHg), and dP/dtmax (1,660 ± 154 to 1,490 ± 160 mmHg/s and 1,595 ± 155 to 1,416 ± 134 mmHg/s) and prolonged ARI (327 ± 18 to 350 ± 23 ms and 327 ± 16 to 347 ± 21 ms, P < 0.05 vs. baseline for all parameters and P = not significant for right VNS vs. left VNS). No anterior-posterior-lateral regional differences in the prolongation of ARI during right or left VNS were found. However, endocardial ARI prolonged more than epicardial ARI, and apical ARI prolonged more than basal ARI during both right and left VNS. Changes in dP/dtmax showed the strongest correlation with ventricular ARI effects (R(2) = 0.81, P < 0.0001) than either heart rate (R(2) = 0.58, P < 0.01) or left ventricular pressure (R(2) = 0.52, P < 0.05). Therefore, right and left VNS have similar effects on ventricular ARI, in contrast to sympathetic stimulation, which shows regional differences. The decrease in inotropy correlates best with ventricular electrophysiological effects.