Ross Upton

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

Data-driven shape parameterization for segmentation of the right ventricle from 3D+t echocardiography

Model-based segmentation facilitates the accurate measurement of geometric properties of anatomy from ultrasound images. Regularization of the model surface is typically necessary due to the presence of noisy and incomplete boundaries. When simple regularizers are insufficient, linear basis shape models have been shown to be effective. However, for problems such as right ventricle (RV) segmentation from 3D+t echocardiography, where dense consistent landmarks and complete boundaries are absent, acquiring accurate training surfaces in dense correspondence is difficult. As a solution, this paper presents a framework which performs joint segmentation of multiple 3D+t sequences while simultaneously optimizing an underlying linear basis shape model. In particular, the RV is represented as an explicit continuous surface, and segmentation of all frames is formulated as a single continuous energy minimization problem. Shape information is automatically shared between frames, missing boundaries are implicitly handled, and only coarse surface initializations are necessary. The framework is demonstrated to successfully segment both multiple-view and multiple-subject collections of 3D+t echocardiography sequences, and the results confirm that the linear basis shape model is an effective model constraint. Furthermore, the framework is shown to achieve smaller segmentation errors than a state-of-art commercial semi-automatic RV segmentation package.

B Postnatal Cardiac Remodelling after Preterm Birth: Why Preterm-Born Individuals have a Unique Functional and Structural Phenotype in Young Adulthood?

Background Preterm birth leads to a switch from fetal to postnatal circulation before completion of in utero cardiac development. We hypothesised that those born preterm would have a unique adult cardiac phenotype and that this would develop during postnatal life. Methods 234 young adults underwent cardiovascular magnetic resonance, of which 102 had been followed prospectively since preterm birth. We then studied 200 infants, longitudinally from birth to three months of age using echocardiography, of which 111 were born preterm. To define cardiac shape and function in adult and neonatal life we developed in-house 3D computational approaches and applied novel deformation imaging tools. Results born preterm had increased LV and RV mass index (P < 0.001 and P < 0.001), proportional to severity of prematurity (P = 0.03 and P < 0.001), and reduced chamber volumes and length (P < 0.01). Although LV ejection fraction was preserved, RV ejection fraction was reduced (P = 0.006), as were LV systolic and diastolic myocardial deformation. At birth, preterm-born infants had similar LV mass index, appropriate for gestational body size, as term-born infants (P = 0.13). However, by three months a greater percentage increase (P = 0.01) resulted in significantly greater LV mass index in those born preterm (P = 0.04). Interestingly, their LV end-diastolic volume index was already smaller at birth (P = 0.003) and this difference persisted at three months (P = 0.05). Conclusions Birth is associated with a unique adult cardiac phenotype. Disproportionate increases in mass occur during postnatal life alongside persistent shape changes. Postnatal life may be a critical window for modification of cardiac development, relevant to the adult cardiovasculature.

Neonatal autonomic function after pregnancy complications and early cardiovascular development

BackgroundHeart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period.MethodsNinety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age.ResultsIncreasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p < 0.001, p = 0.009 and p = 0.007, respectively). We also demonstrated a relative imbalance between sympathetic and parasympathetic tone, compared to the term infants. However, differences in autonomic function did not predict cardiovascular measures at either time point.ConclusionsAltered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk.

Artificial intelligence: a new clinical support tool for stress echocardiography.

Echocardiography remains the imaging modality of choice for the early detection and diagnosis of cardiovascular disease because it is portable, non-invasive, radiation-free, and allows real time imaging of the heart. Furthermore, echocardiography is relatively inexpensive when compared with other imaging modalities and so is accessible in the majority of healthcare settings around the world [1]. However, accurate diagnosis using echocardiography requires a high level of clinical skill and operator training to ensure good quality image acquisition, optimization and interpretation. Wide implementation of echocardiography guidelines have helped standardize these processes and ensured reproducible echocardiographic parameters. However interpretation remains dependent on operator experience and a limited set of echocardiography parameters [2]. Computational tools that allow complex, standardized analysis and quantification of images have emerged, which provide more comprehensive characterization of cardiac structure and function [3,4]. However, it is the combination of these approaches with artificial intelligence tools, such as deep learning, which can form the foundations of a new era of consistent and accurate echocardiography image interpretation.

Two-Dimensional Echocardiography Estimates of Fetal Ventricular Mass throughout Gestation

Background: Two-dimensional (2D) ultrasound quality has improved in recent years. Quantification of cardiac dimensions is important to screen and monitor certain fetal conditions. We assessed the feasibility and reproducibility of fetal ventricular measures using 2D echocardiography, reported normal ranges in our cohort, and compared estimates to other modalities. Methods: Mass and end-diastolic volume were estimated by manual contouring in the four-chamber view using TomTec Image Arena 4.6 in end diastole. Nomograms were created from smoothed centiles of measures, constructed using fractional polynomials after log transformation. The results were compared to those of previous studies using other modalities. Results: A total of 294 scans from 146 fetuses from 15+0 to 41+6 weeks of gestation were included. Seven percent of scans were unanalysable and intraobserver variability was good (intraclass correlation coefficients for left and right ventricular mass 0.97 [0.87-0.99] and 0.99 [0.95-1.0], respectively). Mass and volume increased exponentially, showing good agreement with 3D mass estimates up to 28 weeks of gestation, after which our measurements were in better agreement with neonatal cardiac magnetic resonance imaging. There was good agreement with 4D volume estimates for the left ventricle. Conclusion: Current state-of-the-art 2D echocardiography platforms provide accurate, feasible, and reproducible fetal ventricular measures across gestation, and in certain circumstances may be the modality of choice.

MYOCARDIAL AND FLUID MECHANICS BY ECHOCARDIOGRAPHY DETECT SUBCLINICAL CHANGES IN TYPE 2 DIABETES MELLITUS

Introduction Patients with type 2 diabetes mellitus (T2DM) are at increased risk of heart failure and early identification subtle changes may allow preventive interventions. Altered ventricular myocardial and fluid mechanics are early manifestations of cardiac dysfunction and can be quantified by novel echocardiography techniques. Objective We aimed to assess whether echocardiographic measures of myocardial and fluid mechanics are altered in patients with T2DM. Methods 34 patients (mean age 54.52 ± 8.3) with uncomplicated T2DM and 22 healthy volunteers (mean age 52.50 ± 12.7) were studied. Echocardiography (Philips ie33) was used to quantify vortex formation time (VFT), a measure of fluid dynamics related to left ventricular geometry and early diastolic mitral flow. 3D datasets were used to quantify axial strain (TomTec) and principal strain (S1), secondary strain (S2) and variability of strain within the myocardium via a dedicated MatLab program. Results VFT was significantly reduced (p = 0.00003) in patients with T2DM and correlated with the ratio of S1 to S2 (r = 0.45 p = 0.002), consistent with an impact of vortex formation on systolic efficiency (Table 1). T2DM was associated with altered myocardial systolic mechanics with reduced S2 (p = 0.004) and increased variability of S1 (p = 0.009) and S2 (p = 0.004) (Figure 1). Interobserver variability for measures of VFT, S1 and S2 was low compared with the traditional axial deformation measures. Abstract 123 Table 1 Imaging derived parameters in T2DM participants vs healthy controls T2DM Healthy controls P Value 3D echocardiographic features S1 Peak -0.26 ± 0.07 -0. 29 ± 0.05 0.17 S2 Peak -0.09 ± 0.05 -0.13 ± 0.04 0.01 S1 Variability 0.48 ± 0.14 0.37 ± 0.11 0.009 S2 Variability 1.23 ± 0.88 0.62 ± 0.39 0.004 S Ratio 0.27 ± 0.19 0.42 ± 0.12 0.004 GLS -13.00 ± 2.54 -17.70 ± 2.85 0.001 GCS -21.24 ± 5.93 22.93 ± 5.18 0.34 GRS 30.28 ± 7.39 33.39 ± 5.86 0.15 2D echocardiographic features EF (%) 67.97 ± 6.20 69.55 ± 6.40 0.37 E/A ratio (cm/sec) 0.99 ± 0.25 1.22 ± 0.39 0.03 E/E’ septal (cm/sec) 9.91 ± 2.86 8.72 ± 2.74 0.17 PVs/PVd (cm/sec) 1.07 ± 0.69 1.36 ± 0.34 0.62 PVa (m/s) 0.37 ± 0.11 0.26 ± 0.07 0.001 IVRT (sec) 0.10 ± 0.02 0.08 ± 0.02 0.002 VFT 1.53 ± 0.78 3.02 ± 1.28 0.00003 Abstract 123 Figure 1 Ventricular model (left) and bulls-eye plot (right) of principal strain in healthy control (above) and T2DM patient (below). S1 intensity, represented by colour, is consistent and uniform in the control participant compared to T2DM which shows areas of intense yellow representing high S1 and darker areas representing lower S1, therefore increased S1 variability Conclusion Subclinical changes in myocardial mechanical and ventricular fluid dynamics are identifiable with echocardiography in patients with T2DM. Furthermore, a reduction in VFT is associated with impaired myocardial mechanics.