A preconception lifestyle intervention in women with obesity and cardiovascular health in their children.

BACKGROUND: Maternal obesity during pregnancy is associated with poorer cardiovascular health (CVH) in children. A strategy to improve CVH in children could be to address preconception maternal obesity by means of a lifestyle intervention. We determined if a preconception lifestyle intervention in women with obesity improved offspring's CVH, assessed by magnetic resonance imaging (MRI). METHODS: We invited children born to women who participated in a randomised controlled trial assessing the effect of a preconception lifestyle intervention in women with obesity. We assessed cardiac structure, function and geometric shape, pulse wave velocity and abdominal fat tissue by MRI. RESULTS: We included 49 of 243 (20.2%) eligible children, 24 girls (49%) girls, mean age 7.1 (0.8) years. Left ventricular ejection fraction was higher in children in the intervention group as compared to children in the control group (63.0% SD 6.18 vs. 58.8% SD 5.77, p = 0.02). Shape analysis showed that intervention was associated with less regional thickening of the interventricular septum and less sphericity. There were no differences in the other outcomes of interest. CONCLUSION: A preconception lifestyle intervention in women with obesity led to a higher ejection fraction and an altered cardiac shape in their offspring, which might suggest a better CVH. IMPACT: A preconception lifestyle intervention in women with obesity results in a higher ejection fraction and an altered cardiac shape that may signify better cardiovascular health (CVH) in their children. This is the first experimental human evidence suggesting an effect of a preconception lifestyle intervention in women with obesity on MRI-derived indicators of CVH in their children. Improving maternal preconception health might prevent some of the detrimental consequences of maternal obesity on CVH in their children.

Correction: Linking statistical shape models and simulated function in the healthy adult human heart.

[This corrects the article DOI: 10.1371/journal.pcbi.1008851.].

Linking statistical shape models and simulated function in the healthy adult human heart.

Cardiac anatomy plays a crucial role in determining cardiac function. However, there is a poor understanding of how specific and localised anatomical changes affect different cardiac functional outputs. In this work, we test the hypothesis that in a statistical shape model (SSM), the modes that are most relevant for describing anatomy are also most important for determining the output of cardiac electromechanics simulations. We made patient-specific four-chamber heart meshes (n = 20) from cardiac CT images in asymptomatic subjects and created a SSM from 19 cases. Nine modes captured 90% of the anatomical variation in the SSM. Functional simulation outputs correlated best with modes 2, 3 and 9 on average (R = 0.49 ± 0.17, 0.37 ± 0.23 and 0.34 ± 0.17 respectively). We performed a global sensitivity analysis to identify the different modes responsible for different simulated electrical and mechanical measures of cardiac function. Modes 2 and 9 were the most important for determining simulated left ventricular mechanics and pressure-derived phenotypes. Mode 2 explained 28.56 ± 16.48% and 25.5 ± 20.85, and mode 9 explained 12.1 ± 8.74% and 13.54 ± 16.91% of the variances of mechanics and pressure-derived phenotypes, respectively. Electrophysiological biomarkers were explained by the interaction of 3 ± 1 modes. In the healthy adult human heart, shape modes that explain large portions of anatomical variance do not explain equivalent levels of electromechanical functional variation. As a result, in cardiac models, representing patient anatomy using a limited number of modes of anatomical variation can cause a loss in accuracy of simulated electromechanical function.

The 'Digital Twin' to enable the vision of precision cardiology.

Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the 'digital twin' of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine.

Cardiac Arrest in Acute Myocardial Infarction: Concept of Circulatory Support With Mechanical Chest Compression and Impella to Facilitate Percutaneous Coronary Intervention.

Cardiogenic shock in the context of acute ST-elevation myocardial infarction (STEMI) remains a challenge to manage and results in significant mortality and morbidity, cardiac arrest in this setting even more so. The increase in myocardial oxygen demand and consumption with the use of inotropes is recognised as increasing mortality. Alternatives include the intra-aortic balloon pump (IABP), which has yet to be shown to improve outcomes, and extracorporeal membrane oxygenation (ECMO), which requires super-specialised techniques not widely available. We report a case of Anterior STEMI from a left main stem occlusion suffering with cardiac arrest on reaching the catheter laboratory table necessitating external mechanical compression with an Autopulse™. The patient remained in pulseless electrical activity (PEA) throughout, and was Autopulse dependent despite successful percutaneous coronary intervention (PCI). An Impella® was inserted for additional mechanical support and facilitated successful weaning from cardiopulmonary resuscitation (CPR). Despite 105minutes without a spontaneous output, we describe the first documented case of simultaneous use of Impella with mechanical CPR with a successful outcome; demonstrating a potential technique of good mechanical haemodynamic support to aide early revascularisation that may have potential utility in the treatment of cardiogenic shock and arrest.

Antegrade Dissection Re-entry for Management of Retained Microcatheter Tips During PCI for Chronic Total Occlusion: A Case Series.

Application of the hybrid algorithm for the treatment of coronary chronic total occlusions requires the operator to readily deploy complex techniques and advanced technologies to achieve successful revascularization. Patient-specific factors and limitations in torquability and material strength of low-profile equipment such as microcatheters can result in procedural complications due to device fracture. Using a mini-series of 2 cases to demonstrate the successful application of antegrade dissection re-entry techniques to overcome such challenges, we highlight procedural complexities and risk, and review prior approaches and literature.

A three-dimensional atlas of child's cardiac anatomy and the unique morphological alterations associated with obesity.

AIMS: Statistical shape models (SSMs) of cardiac anatomy provide a new approach for analysis of cardiac anatomy. In adults, specific cardiac morphologies associate with cardiovascular risk factors and early disease stages. However, the relationships between morphology and risk factors in children remain unknown. We propose an SSM of the paediatric left ventricle to describe its morphological variability, examine its relationship with biometric parameters and identify adverse anatomical remodelling associated with obesity. METHODS AND RESULTS: This cohort includes 2631 children (age 10.2 ± 0.6 years), mostly Western European (68.3%) with a balanced sex distribution (51.3% girls) from Generation R study. Cardiac magnetic resonance short-axis cine scans were segmented. Three-dimensional left ventricular (LV) meshes are automatically fitted to the segmentations to reconstruct the anatomies. We analyse the relationships between the LV anatomical features and participants' body surface area (BSA), age, and sex, and search for features uniquely related to obesity based on body mass index (BMI). In the SSM, 19 modes described over 90% of the population's LV shape variability. Main modes of variation were related to cardiac size, sphericity, and apical tilting. BSA, age, and sex were mostly correlated with modes describing LV size and sphericity. The modes correlated uniquely with BMI suggested that obese children present with septo-lateral tilting (R2 = 4.0%), compression in the antero-posterior direction (R2 = 3.3%), and decreased eccentricity (R2 = 2.0%). CONCLUSIONS: We describe the variability of the paediatric heart morphology and identify anatomical features related to childhood obesity that could aid in risk stratification. Web service is released to provide access to the new shape parameters.

Generating Synthetic Labeled Data From Existing Anatomical Models: An Example With Echocardiography Segmentation.

Deep learning can bring time savings and increased reproducibility to medical image analysis. However, acquiring training data is challenging due to the time-intensive nature of labeling and high inter-observer variability in annotations. Rather than labeling images, in this work we propose an alternative pipeline where images are generated from existing high-quality annotations using generative adversarial networks (GANs). Annotations are derived automatically from previously built anatomical models and are transformed into realistic synthetic ultrasound images with paired labels using a CycleGAN. We demonstrate the pipeline by generating synthetic 2D echocardiography images to compare with existing deep learning ultrasound segmentation datasets. A convolutional neural network is trained to segment the left ventricle and left atrium using only synthetic images. Networks trained with synthetic images were extensively tested on four different unseen datasets of real images with median Dice scores of 91, 90, 88, and 87 for left ventricle segmentation. These results match or are better than inter-observer results measured on real ultrasound datasets and are comparable to a network trained on a separate set of real images. Results demonstrate the images produced can effectively be used in place of real data for training. The proposed pipeline opens the door for automatic generation of training data for many tasks in medical imaging as the same process can be applied to other segmentation or landmark detection tasks in any modality. The source code and anatomical models are available to other researchers.1 1https://adgilbert.github.io/data-generation/.

Septal curvature as a robust and reproducible marker for basal septal hypertrophy.

BACKGROUND: Basal septal hypertrophy (BSH) is an asymmetric, localized thickening of the upper interventricular septum and constitutes a marker of an early remodelling in patients with hypertension. This morphological trait has been extensively researched because of its prevalence in hypertension, yet its clinical and prognostic value for individual patients remains undetermined. One of the reasons is the lack of a reliable and reproducible metric to quantify the presence and the extent of BSH. This article proposes the use of the curvature of the left ventricular endocardium as a robust feature for BSH characterization, and as an objective criterion to quantify current subjective 'visual assessment' of the presence of sigmoidal septum. The proposed marker, called average septal curvature, is defined as the inverse of the radius adjacent to each point of the endocardial contour along the basal and mid inferoseptal segments of the left ventricle. METHOD: Robustness and reproducibility were assessed on a cohort of 220 patients, including 161 hypertensive patients (32 with BSH) and 59 healthy controls. RESULTS: The results show that compared with the conventionally used wall thickness metrics, the new marker is more reproducible (relative standard deviation of errors of 7 vs. 13%, and 8 vs. 38% for intra-observer and inter-observer variability, respectively) and better correlates to the functional parameters related to BSH, with main difference (absolute rank correlation 0.417 vs. 0.341) in local deformation changes assessed by longitudinal strain. CONCLUSION: Average septal curvature is a more precisely defined and reproducible metric than thickness ratios, it can be fully automated, and better infers the functional remodelling related to hypertension.

Association of Systolic Blood Pressure Elevation With Disproportionate Left Ventricular Remodeling in Very Preterm-Born Young Adults: The Preterm Heart and Elevated Blood Pressure.

Importance: Preterm-born individuals have higher blood pressure with an increased risk of hypertension by young adulthood, as well as potentially adverse cardiac remodeling even when normotensive. To what extent blood pressure elevation affects left ventricular (LV) structure and function in adults born preterm is currently unknown. Objective: To investigate whether changes observed in LV structure and function in preterm-born adults make them more susceptible to cardiac remodeling in association with blood pressure elevation. Design, Setting, and Participants: This cross-sectional cohort study, conducted at the Oxford Cardiovascular Clinical Research Facility and Oxford Centre for Clinical Magnetic Resonance Research, included 468 adults aged 18 to 40 years. Of these, 200 were born preterm (<37 weeks' gestation) and 268 were born at term (≥37 weeks' gestation). Cardiac magnetic resonance imaging was used to characterize LV structure and function, with clinical blood pressure readings measured to assess hypertension status. Demographic and anthropometric data, as well as birth history and family medical history information, were collected. Data were analyzed between January 2012 and February 2021. Main Outcomes and Measures: Cardiac magnetic resonance measures of LV structure and function in response to systolic blood pressure elevation. Results: The cohort was primarily White (>95%) with a balanced sex distribution (51.5% women and 48.5% men). Preterm-born adults with and without hypertension had higher LV mass index, reduced LV function, and smaller LV volumes compared with term-born individuals both with and without hypertension. In regression analyses of systolic blood pressure with LV mass index and LV mass to end-diastolic volume ratio, there was a leftward shift in the slopes in preterm-born compared with term-born adults. Compared with term-born adults, there was a 2.5-fold greater LV mass index per 1-mm Hg elevation in systolic blood pressure in very and extremely preterm-born adults (<32 weeks' gestation) (0.394 g/m2 vs 0.157 g/m2 per 1 mm Hg; P < .001) and a 1.6-fold greater LV mass index per 1-mm Hg elevation in systolic blood pressure in moderately preterm-born adults (32 to 36 weeks' gestation) (0.250 g/m2 vs 0.157 g/m2 per 1 mm Hg; P < .001). The LV mass to end-diastolic volume ratio per 1-mm Hg elevation in systolic blood pressure in the very and extremely preterm-born adults was 3.4-fold greater compared with those born moderately preterm (3.56 × 10-3 vs 1.04 × 10-3 g/mL per 1 mm Hg; P < .001) and 3.3-fold greater compared with those born at term (3.56 × 10-3 vs 1.08 × 10-3 g/mL per 1 mm Hg; P < .001). Conclusions and Relevance: Preterm-born adults have a unique LV structure and function that worsens with systolic blood pressure elevation. Additional primary prevention strategies specifically targeting cardiovascular risk reduction in this population may be warranted.

Distribution of myocardial work in arterial hypertension: insights from non-invasive left ventricular pressure-strain relations.

A index of non-invasive myocardial work (MWI) can account for pressure during the assessment of cardiac function, potentially separating the influence of loading conditions from the influence of the underlying tissue remodelling. The aim is to assess LV function accounted for loading and explore hypertensive MWI distribution by comparing healthy individuals to hypertensive patients without and with localized basal septal hypertrophy (BSH). An echocardiogram was performed in 170 hypertensive patients and 20 healthy individuals. BSH was defined by a basal-to-mid septal wall thickness ratio ≥ 1.4. LV speckle-tracking was performed, and the MWI calculated globally and regionally for the apical, mid and basal regions. An apex-to-base gradient, seen in regional strain values, was preserved in the distribution of myocardial work, with the apical region compensating for the impairment of the basal segments. This functional redistribution was further pronounced in patients with localized BSH. In these patients, segmental MWI analysis revealed underlying impairment of regional work unrelated to acute loading conditions. Non-invasive MWI analysis offers the possibility to compare LV function regardless of blood pressure at the time of observation. Changes in MWI distribution can be seen in hypertension unrelated to the load-dependency of strain. Accentuated functional changes affirm the role of BSH as an echocardiographic marker in hypertension.

Toward understanding response to cardiac resynchronization therapy: left ventricular dyssynchrony is only one of multiple mechanisms.

AIM: To date, most published echocardiographic methods have assessed left ventricular (LV) dyssynchrony (DYS) alone as a predictor for response to cardiac resynchronization therapy (CRT). We hypothesized that the response is instead dictated by multiple correctable factors. METHODS AND RESULTS: A total of 161 patients (66 +/- 10 years, EF 24 +/- 6%, QRS > 120 ms) were investigated pre- and post-CRT (median of 6 months). Reduction in NYHA Class >/=1 or LV reverse remodelling (end-systolic volume reduction >/= 10%) defined response. Four different pathological mechanisms were identified. Group1: LVDYS characterized by a pre-ejection septal flash (SF) (87 patients, 54%). Elimination of SF (77 of 87 patients) resulted in reverse remodelling in 100%. Group 2: short-AV delay (21 patients, 13%) resolution (19 of 21 patients) resulted in reverse remodelling in 16 of 19. Group 3: long-AV delay (16 patients, 10%) resolution (14 of 16 patients) resulted in NYHA Class reduction >/=1 in 11 with reverse remodelling in five patients. Group 4: exaggerated LV-RV interaction (15 patients, 9%) reduced post-CRT. All responded clinically with fall in pulmonary artery pressure (P = 0.003) but did not volume respond. Group 5: patients with none of the above correctable mechanisms (22 patients, 14%). None responded to CRT. CONCLUSION: CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.

Basal Ventricular Septal Hypertrophy in Systemic Hypertension.

Basal septal hypertrophy (BSH) is commonly seen in patients with systemic hypertension and has been associated with increased afterload. The impact of localized hypertrophy on left ventricular (LV) and left atrial (LA) function is still unclear. Our aim is to investigate if BSH is a marker of a more pronounced impact of hypertension on cardiac function in the early stages of hypertensive heart disease. An echocardiogram was performed in 163 well-controlled hypertensive patients and 22 healthy individuals. BSH was defined by a basal-to-mid septal thickness ratio ≥1.4. LV dimensions and mass were evaluated. LV global and regional deformation was assessed by 2-dimensional (2D) speckle tracking echocardiography, and LV diastolic function by 2D and Doppler imaging. LA function was evaluated with phasic volume indices calculated from 2D and 3-dimensional volumes, as well as speckle tracking echocardiography. The population was 54% men, mean age 57 (53 to 60) years. BSH was seen in 20% (n = 32) of the hypertensive cohort. Patients with BSH showed decreased regional LV systolic deformation, impaired LV relaxation with a higher proportion of indeterminate LV diastolic function, and LA functional impairment defined by a reduction of reservoir strain and a change in LA functional dynamics. In conclusion, in well-controlled hypertension impairment of LV and LA function is present in patients with early LV remodeling and localized hypertrophy. BSH might be useful as an early marker of the burden of hypertensive heart disease.

Myocardial deformation abnormalities in patients with aortic regurgitation: a strain rate imaging study.

AIMS: Early left ventricular (LV) dysfunction in asymptomatic patients with severe aortic regurgitation (AR) may go undetected due to the lack of a sufficiently sensitive diagnostic tool. Ultrasonic strain/strain rate (S/SR) imaging should now provide such sensitivity in detecting early dysfunction in regional LV systolic deformation. The aim of this study was to understand and define the changes in LV regional systolic deformation based on S/SR imaging in patients with asymptomatic or minimally symptomatic AR. METHODS AND RESULTS: Eighty-one individuals were studied: 59 asymptomatic patients with isolated non-ischaemic AR who were divided into three sub-groups such as mild, moderate, and severe AR and 22 age-matched healthy subjects. All patients underwent standard echocardiographic examinations including a tissue Doppler imaging study. For LV radial deformation, the posterior wall (LVPW) was examined. To assess LV longitudinal deformation, S and SR data were acquired from the LV lateral wall and septum. Radial as well as longitudinal peak systolic SRs were significantly decreased in patients with both moderate AR (LVPW, P=0.0009; septum, P=0.03; LV lateral wall, P=0.0009) and severe AR (P<0.0001) compared with healthy subjects. Changes in regional LV deformation correlated inversely both with LV end-diastolic volume and with end-systolic volume. CONCLUSIONS: Strain rate imaging is a sensitive tool in detecting the spectrum of changes in radial and longitudinal deformation in asymptomatic or minimally symptomatic patients with AR. The index where volume was corrected by deformation should form the basis for predicting subclinical LV dysfunction in patients with increasing LV dilatation.

Regional left ventricular deformation and geometry analysis provides insights in myocardial remodelling in mild to moderate hypertension.

AIM: In the early stages of hypertension (HTN), when global left ventricular (LV) function is still unaffected, localized geometrical changes suggest changes in regional function. We investigated regional geometry and systolic deformation (using strain/strain rate (S/SR) imaging) in HTN. METHODS AND RESULTS: We studied 74 untreated mild to moderate HTNs and 34 matched normotensives (NTN). All had a standard echo including myocardial velocity data for regional radial and longitudinal deformation. Despite the absence of abnormalities in standard functional indices and LVH, non-uniform changes in regional geometry and deformation were observed. Besides a significant increase in wall thickness (WT) in all HTN segments, there was a gradual increase in WT from apex to base resulting in prominent basal septal hypertrophy. In HTN, regional longitudinal peak systolic SR (SSR) and end-systolic S (ESS) were significantly (P < 0.0001) reduced in the basal septum. In the lateral wall there was an increase in peak SSR and ESS (P < 0.05) basally. The basal septal ESS correlated both with mean arterial pressure and basal septal WT, with lower ESS for higher BP and thicker septum. CONCLUSION: Regionally differing geometrical remodelling occurs early in HTN. Longitudinal ESS and peak SSR are sensitive markers of early changes occurring in HTN.

Full or pressure limited reperfusion of an acute myocardial infarct results in a different wall thickness and deformation of the distal myocardium--implications for clinical reperfusion strategies.

AIM: The study aim was to determine the sequence of changes in both wall thickness and function in 'at risk' myocardium (using M-mode and radial strain/strain-rate imaging) induced by reperfusion of an acute transmural infarction, and to relate these changes to the presence or absence of a pressure-limiting stenosis in the infarct related epicardial vessel. METHODS: Eighteen closed-chest pigs were randomized into two groups (each with nine animals). In Group I, 4 weeks prior to induction of an acute transmural infarct, a copper coated stent was implanted in the proximal circumflex artery (Cx) to create a coronary artery stenosis of between 30 and 95% lumen diameter. At 4 weeks, the stenotic Cx vessel was occluded for 90 min by inflation of a PTCA balloon placed proximal to the stenosis to produce an acute transmural infarction. In Group II (the control group), 90 min Cx occlusion was performed in a normal vessel. In both groups the resulting acute transmural infarction was reperfused after 90 min by removing the PTCA balloon. For both groups, cardiac ultrasound data, including strain/strain-rate imaging, were collected at all stages of the investigation for subsequent offline analysis. RESULTS: In both groups, acute reperfusion (TIMI flow 3 or 2), immediately increased infarct zone end-diastolic wall thickness due to the development of oedema. The acute increase in wall thickness was significantly higher in the non-stenotic animals as compared to the ones with a residual stenosis. Neither of the groups showed any tendency to normalize deformation (strain) during the reperfusion period. CONCLUSION: In this experimental study, the measurement of end-diastolic wall thickness was a simple and non-invasive tool to monitor acute infarct reperfusion. It also provided information on the presence of a flow limiting stenosis in the infarct related artery after restoration of the flow. The deformation of the myocardium remained impaired during early reperfusion, whether reflow was at full pressure or low pressure due to a residual stenosis in the infarct related artery.

Thrombus aspiration in acute myocardial infarction: concepts, clinical trials, and current guidelines.

The pathogenesis that underlies acute myocardial infarction is complex and multifactorial. One of the most important components, however, is the role of thrombus formation following atherosclerotic plaque rupture, leading to sudden coronary occlusion and subsequent ischemia and infarction. Thrombus aspiration provides the opportunity of intracoronary clot extraction with the aim to improve coronary and myocardial perfusion, by reducing the risk of no-reflow secondary to distal embolization of thrombus. The utility of thrombus aspiration during primary percutaneous coronary intervention has been assessed in an increasing number of observational and randomized studies. This article reviews the contemporary data and provides insights into the validity of thrombus aspiration in the setting of acute myocardial infarction.

Prediction of postoperative left ventricular systolic function in patients with chronic mitral regurgitation undergoing valve surgery--the role of deformation imaging.

OBJECTIVE: Preoperative left ventricular systolic function is an important prognostic factor in patients undergoing mitral valve surgery. Preoperative myocardial deformation may be impaired without reduction in conventional indices such as ejection fraction (EF). Strain rate (SR) imaging is very sensitive in detecting regional systolic abnormalities and might allow diagnosis of subclinical changes in systolic left ventricular (LV) function before surgery. We aimed to investigate the value of preoperative regional myocardial peak systolic SR as a predictor of postoperative LV systolic function in patients with severe mitral regurgitation (MR) undergoing surgery. METHODS: A total of 62 patients (age 52±12) with chronic severe MR, who underwent mitral valve repair, were studied. A standard echo examination, extended with tissue Doppler, was performed before and at 12 months after surgery. For the evaluation of longitudinal function, mid-ventricular segment shortening was analysed for the septum, LV lateral wall and anterior and inferior walls. RESULTS: Patients were divided into two groups based on postoperative EF: group 1 with EF(post-op)>50% and group 2 with EF(post-op)<50%. Group 1 had a significantly (p=0.004) higher preoperative SR (LV lateral wall: -1.97±0.26s(-1); septum: -1.74±0.31s(-1); anterior wall: -1.94±0.30s(-1), inferior wall: -1.93±0.29s(-1)) compared to group 2 (LV lateral wall: -0.98±0.23s(-1); septum: -0.98±0.26s(-1); anterior wall: -0.94±0.30s(-1), inferior wall: -1.00±0.24s(-1)). When SR was corrected for size, the SR/EDV index (EDV is end diastolic volume) also showed significant changes (p=0.0007) at baseline between the groups. For detecting subclinical changes in deformation of the LV lateral wall, a cut-off value of the SR/EDV index<0.006 had 89% sensitivity and 93% specificity; for the anterior wall, SR/EDV index<0.005 had 88% sensitivity and 94% specificity. CONCLUSIONS: SR imaging (corrected for geometry) can detect abnormalities in LV function at subclinical levels in patients with severe mitral regurgitation.