Impaired myocardial deformation persists at 2 years in offspring of mothers with diabetes mellitus.

BACKGROUND: A diabetic intrauterine environment has been proposed as a potential etiological mechanism for in utero programming of cardiac disease, and is associated with impaired fetal cardiac function. We aimed to assess cardiac function in offspring of mothers with diabetes mellitus (ODM) and determine whether fetal cardiac abnormalities persist during follow-up. METHODS: Longitudinal observational study to evaluate and compare myocardial function in 40 ODM to age-matched control offspring (CO). Myocardial deformation was measured using speckle-tracking echocardiography (STE). RESULTS: Significant differences were detected in global longitudinal strain (-20.9 ± 3.1 vs. -23.6 ± 2.2%; p = 0.001), global circumferential strain (-24.4 ± 3.9 vs. -26.9 ± 2.7%; p = 0.017), average radial strain (29.0 ± 9.8 vs. 37.1 ± 7.2%; p = 0.003), average longitudinal systolic strain rate (-1.24 ± 0.25/s vs. -1.47 ± 0.30/s; p = 0.011) and average circumferential systolic strain rate (-1.56 ± 0.37/s vs. -1.84 ± 0.37/s; p = 0.013) in comparison to CO up to 2 years of follow-up. Minimal differences were observed within ODM over the 2-year period. CONCLUSION: Impaired cardiac function in ODM persists during 2 years follow-up. Functional cardiac assessment might therefore be useful to detect these unfavorable changes, independent of screening for congenital heart disease or hypertrophic cardiomyopathy in this population. IMPACT: We demonstrate persistence of subclinical myocardial deformation abnormalities in offspring of mothers with diabetes mellitus from fetal life to early childhood years. These results extend the cellular observations in basic and translational research of developmental programming into the clinical realm. Persistence of subclinical myocardial deformation abnormalities may shed light on the known incidence of early cardiovascular disease in offspring of mother with diabetes. Cardiac myocardial strain assessment can be useful to detect these abnormalities, independent of screening for congenital heart disease or hypertrophic cardiomyopathy in this population.

Sleep-related breathing disorders and cardiometabolic risk factors in pediatric kidney transplant recipients.

BACKGROUND: SRBDs have been shown to increase the risk of cardiovascular disease, which is a significant cause of mortality in kidney transplant recipients. Few studies have investigated the association between SRBDs and cardiometabolic risk factors in pediatric kidney transplant recipients. METHODS: This was a cross-sectional study of pediatric kidney transplant recipients using baseline cardiometabolic data from a previous clinical trial (NCT01007994). Parents/guardians of pediatric kidney transplant recipients filled out 22-item PSQ. A score greater than 33% was defined as a diagnosis of a SRBD. Fisher's exact test, Mann-Whitney U test, and regressions were used to determine associations. RESULTS: Among the 58 transplant recipients enrolled, 14.80% (n = 8) of participants identified as Black and 40.7% (n = 22) were male. The median age was 13 (IQR 8.25, 17) years and median number of years post-transplant for participants was 2 (IQR 1, 4). The prevalence of SRBDs was 26% (n = 14). The presence of a SRBD was associated with abnormalities in multiple cardiometabolic risk factors including total cholesterol level (ß = 23.63; 95% CI 3.58-43.67), LDL level (ß = 24.94; 95% CI 6.37-43.50), triglyceride level (ß = 54.62; 95% CI 8.74-100.50), and LVH (OR = 5.12; 95% CI 1.12-23.45) when adjusted for age, sex, and race. CONCLUSIONS: Similar to associations reported in the general pediatric and general CKD populations, SRBD is associated with increased cardiometabolic risk in pediatric kidney transplant recipients.

Restoration of nocturnal blood pressure dip and reduction of nocturnal blood pressure with evening anti-hypertensive medication administration in pediatric kidney transplant recipients: A pilot randomized clinical trial.

Non-dipping and nocturnal hypertension are commonly found during ABPM in pediatric kidney transplant recipients. These entities are independently associated with increased cardiovascular disease risk in adults. Kidney transplant recipients aged 5-21 years with eGFR > 30 mL/min/1.73 m2 and ABPM demonstrating non-dipping status and normal daytime BP were randomized to intervention (short acting BP medication added in the evening) or control (no medication change) in this pilot, randomized, open-label, blinded end-point clinical trial. ABPM, echocardiography, and PWV were performed at baseline, 3 months, and 6 months. The trial included 17 intervention and 16 control participants. Conversion to dipper status occurred in 53.3% vs 7.7% (P = .01) at 6 months for intervention and controls, respectively. Systolic dip was greater in the intervention group compared to controls (10.9 ± 4.5 vs 4.2 ± 4.6, P = .001), and average systolic nighttime BP was significantly lower in the intervention group (106 ± 8.3 vs 114.9 ± 9.5 mm Hg, P = .01) at 6 months. There were no significant differences in LVMI, PWV, or eGFR between groups. Within-group changes in the intervention group demonstrated improvements in non-dippers, dipping, systolic nighttime BP and nighttime BP load. Restoration of nocturnal dip and improvement in nocturnal BP were observed in the population following chronotherapy. Future studies are needed with larger sample sizes over a longer period of time to delineate the long-term effect of improved nocturnal dip on target organ damage.

Myocardial ischaemia and valve insufficiency caused by a dysplastic aortic valve cusp: a previously unreported unique morphologic anomaly.

Isolated aortic regurgitation and myocardial infarction are a rare congenital defect among neonatal patients. We present a case of a neonate with an unusual aortic valve morphology causing both regurgitation and obstruction of the left coronary artery ostium. Despite both non-invasive and invasive imaging modalities, accurate diagnosis of the valve morphology was only determined by direct visualisation at the time of surgical repair. To the knowledge of authors, this particular aortic valve morphology in neonatal population has not been previously reported in the literature.

Examining the Utility of Coronary Artery Lack of Tapering and Perivascular Brightness in Incomplete Kawasaki Disease.

BACKGROUND: In 2017, the AHA published revised guidelines for the diagnosis of Kawasaki disease (KD). In the absence of compelling data supporting or refuting the utility of lack of tapering (LT) and perivascular brightness (PB), expert panel consensus removed LT and PB from consideration. We hypothesize that LT and PB are unreliable, subjective findings, non-specific to KD, which can be seen in systemic febrile illnesses without KD and in normal controls. METHODS: We performed a single-center retrospective study from 1/2008 to 12/2016. De-identified coronary artery (CA) echocardiographic clips from patients 0-10 years old were interpreted blindly by six pediatric cardiologists. Subjects were grouped as follows: (1) healthy: afebrile with benign murmur, (2) KD: IVIG treatment, 4-5 clinical criteria at presentation, (3) incomplete KD (iKD): IVIG, 1-3 clinical criteria, (4) Febrile: ≥3 days of fever, no IVIG, KD not suspected. The presence or absence of LT and PB was recorded. Inter-rater and intra-rater reliabilities were analyzed using intra-class correlation coefficient, Fleiss' Kappa and Cohen's Kappa coefficients. RESULTS: We interpreted 117 echocardiograms from healthy (27), KD (30), iKD (32), and febrile (28) subjects. Analysis showed moderate agreement in CA z score measurements. LT and PB were observed by most readers in control groups. LT exhibited fair inter-reader agreement (reliability coefficient 0.36) and PB slight inter-reader agreement (reliability coefficient 0.13). Intra-rater reliability was inconsistent for both parameters. CONCLUSIONS: LT and PB are subjective, poorly reproducible features that can be seen in febrile patients without KD and in healthy children.

A detailed comparison of mouse and human cardiac development.

BACKGROUND: Mouse mutants are used to model human congenital cardiovascular disease. Few studies exist comparing normal cardiovascular development in mice vs. humans. We carried out a systematic comparative analysis of mouse and human fetal cardiovascular development. METHODS: Episcopic fluorescence image capture (EFIC) was performed on 66 wild-type mouse embryos from embryonic day (E) 9.5 to birth; 2-dimensional and 3-dimensional datasets were compared with EFIC and magnetic resonance images from a study of 52 human fetuses (Carnegie stage 13-23). RESULTS: Time course of atrial, ventricular, and outflow septation were outlined and followed a similar sequence in both species. Bilateral venae cavae and prominent atrial appendages were seen in the mouse fetus; in human fetuses, atrial appendages were small, and a single right superior vena cava was present. In contrast to humans with separate pulmonary vein orifices, a pulmonary venous confluence with one orifice enters the left atrium in mice. CONCLUSION: The cardiac developmental sequences observed in mouse and human fetuses are comparable, with minor differences in atrial and venous morphology. These comparisons of mouse and human cardiac development strongly support that mouse morphogenesis is a good model for human development.

Macrophage migration inhibitory factor induces cardiomyocyte apoptosis.

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that causes cardiac contractile dysfunction, whereas inactivation of MIF improves cardiac function in experimental animal models of sepsis. We used cultured cardiomyocytes to determine whether MIF-induced contractile dysfunction was mediated in part by myocyte apoptosis and to identify MIF-activated intracellular signaling pathways in this process. MIF treatment significantly increased myocyte apoptosis in a dose-dependent manner to 15.5+/-3.9% and 26.0+/-7.1% TUNEL positive nuclei (20 and 30 ng/ml MIF for 24h) vs control (3.7+/-0.9%). This effect was attenuated by inactivation of MIF with the chemical inhibitor, ISO-1. MIF-induced cleavage of caspase 3 and reduction of Bcl-xL/Bax were similarly attenuated by ISO-1 pre-treatment. MIF stimulated the rapid, transient phosphorylation of stress kinases, p38MAPK and JNK. Thus, MIF induces cardiomyocyte apoptosis by activating stress kinases and mitochondria-associated apoptotic mechanisms, whereas inactivation of MIF pro-inflammatory activity improves cardiomyocyte survival.