Objective To provide a cost minimization analysis to support a paradigm shift in the use of comprehensive ultrasound and echocardiography in the prenatal diagnosis of congenital heart disease (CHD) in fetuses of women with diabetes mellitus (DM). Methods

Fetal chronic anemia causes lengthening of cardiomyocytes. In adults, severe left ventricular overload may lead to irreversible ventricular dysfunction. We hypothesized that in sheep fetuses with chronic anemia, remodeled myocardium would less successfully respond to angiotensin II (AT II) infusion than in fetuses without anemia. A total of 14 ewes with twin pregnancy underwent surgery at 113 ± 1 days of gestation. After a recovery period, anemia was induced by isovolumic hemorrhage in 1 fetus of each pair. At 126 ± 1 days of gestation, longitudinal myocardial velocities of the right (RV) and left (LV) ventricles were assessed at the level of the atrioventricular valve annuli via tissue Doppler imaging. Cardiac outputs were calculated by pulsed Doppler ultrasound. All measurements were performed at baseline and during fetal AT II infusion. Fetal serum cardiac natriuretic peptide (N-terminal peptide of proatrial natriuretic peptide [NT-proANP] and B-type natriuretic peptide [BNP]) concentrations were determined. Nine ewes successfully completed the experiment. At baseline, ventricular free wall thicknesses, cardiac outputs, and NT-proANP levels were significantly greater in the anemic fetuses than in the controls. The LV isovolumic contraction velocity (IVCV) acceleration and isovolumic relaxation velocity (IVRV) deceleration were lower (P < .05) in the anemic fetuses than in the controls. In the anemic fetuses, there was a positive correlation (R = .93, P < .01) between RV IVRV deceleration and NT-proANP concentration. Angiotensin II infusion increased (P < .05) LV IVCV acceleration in the anemic fetuses. We conclude that in anemic sheep fetuses, myocardial adaptation is associated with impaired LV early contraction and relaxation. However, the LV can improve its contractility with an inotropic stimulus, even in the presence of increased afterload.

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Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Ultromics Ltd Introduction Transthoracic echocardiography (TTE) assessment of left ventricular (LV) function has a central role in early detection and treatment of cancer-therapy related cardiac dysfunction (CTRCD). Contrast TTE is recommended to aid accurate and reproducible LV contouring , but contrast agents are underused and high variability remains. Using machine learning (ML) to automatically contour the LV reduces variability, and may provide comparable clinical benefit to contrast-enhanced TTE. Purpose Retrospective single site study evaluating agreement between LV volumes and function from manually contoured contrast-enhanced TTE and automated contouring of non-contrast enhanced images. Methods Adults at risk of developing CTRCD who underwent TTE were recruited. LV volumes (end-diastolic and systolic; EDV and ESV, respectively) and function (ejection fraction; EF) were measured from contrast-enhanced images using manual contouring (MAN-CONT), and non-contrast enhanced images using automation (AUTO-NON). Method comparisons were summarised based on: (i) statistical equivalence (two one-sided t-tests), (ii) systematic difference between methods, via root mean-squared error (RMSE; Deming regression), and (iii) average bias (Bland-Altman). Statistical equivalence bounds were conservatively determined from reproducibility estimates in a similar cohort (EDV, 20 mL; ESV, 15 mL; EF, 5%; REF1), and used to interpret RMSE and bias. Results The cohort comprised of patients undergoing treatment for breast cancer, lymphoma, and myeloma. Similar body mass indices were seen between groups (median [IQR]: 26.5 [6.7] kg/m2; Kruskall-Wallace test, p = 0.320), but breast cancer patients were younger (55.0 [14.5], 58.5 [23], 60 [9], respectively; p = 0.034). For estimates of LV volumes and function, statistical equivalence, RMSE, and bias are presented in Table1. Average estimates (mean [SD]) of EDV, ESV, and EF were 121 [33] vs. 112 [33] mL, 50 [23] vs. 44 [19] mL, and 60 [9] vs. 61 [8]%, for MAN-CON and AUTO-NON respectively. Comparing between MAN-CON and AUTO-NON in breast cancer patients, all variables were statistically equivalent (Figure1), and while bias was lower than equivalence bounds, RMSE was only lower for EDV and ESV, not EF. For lymphoma patients, estimates of EDV were statistically equivalent, but not EF and ESV. Bias was lower than equivalence bounds for all variables, whereas RMSE was lower for ESV, but not EDV or EF. For myeloma patients, estimates of ESV and EF were statistically equivalent, but not EDV. While bias was lower than equivalence bounds for all variables, RMSE was not lower for any variable. Conclusions: Estimates of LV function from automated contouring of non-contrast TTE are similar to contrast-enhanced TTE (manually contoured), despite poorer image quality. Automated contouring using ML reduces variability, therefore increasing TTE sensitivity, which is critical when clinical management relies on accurate assessment of LV function. Abstract Table1  Abstract Figure1