Deep learning to detect left ventricular structural abnormalities in chest X-rays.

BACKGROUND AND AIMS: Early identification of cardiac structural abnormalities indicative of heart failure is crucial to improving patient outcomes. Chest X-rays (CXRs) are routinely conducted on a broad population of patients, presenting an opportunity to build scalable screening tools for structural abnormalities indicative of Stage B or worse heart failure with deep learning methods. In this study, a model was developed to identify severe left ventricular hypertrophy (SLVH) and dilated left ventricle (DLV) using CXRs. METHODS: A total of 71 589 unique CXRs from 24 689 different patients completed within 1 year of echocardiograms were identified. Labels for SLVH, DLV, and a composite label indicating the presence of either were extracted from echocardiograms. A deep learning model was developed and evaluated using area under the receiver operating characteristic curve (AUROC). Performance was additionally validated on 8003 CXRs from an external site and compared against visual assessment by 15 board-certified radiologists. RESULTS: The model yielded an AUROC of 0.79 (0.76-0.81) for SLVH, 0.80 (0.77-0.84) for DLV, and 0.80 (0.78-0.83) for the composite label, with similar performance on an external data set. The model outperformed all 15 individual radiologists for predicting the composite label and achieved a sensitivity of 71% vs. 66% against the consensus vote across all radiologists at a fixed specificity of 73%. CONCLUSIONS: Deep learning analysis of CXRs can accurately detect the presence of certain structural abnormalities and may be useful in early identification of patients with LV hypertrophy and dilation. As a resource to promote further innovation, 71 589 CXRs with adjoining echocardiographic labels have been made publicly available.

Simple model of pulmonary hypertension secondary to left heart pressure overload induced by partial intravascular occlusion of the ascending aorta.

Pulmonary hypertension is a group of diseases characterized by elevated pulmonary artery pressure and pulmonary vascular resistance with significant morbidity and mortality. The most prevalent type is pulmonary hypertension secondary to left heart disease (PH-LHD). The available experimental models of PH-LHD use partial pulmonary clamping by technically nontrivial open-chest surgery with lengthy recovery. We present a simple model in which the reduction of the cross-sectional area of the ascending aorta is achieved not by external clamping but by partial intravascular obstruction without opening the chest. In anesthetized rats, a blind polyethylene tubing was advanced from the right carotid artery to just above the aortic valve. The procedure is quick and easy to learn. Three weeks after the procedure, left heart pressure overload was confirmed by measuring left ventricular end-diastolic pressure by puncture (1.3 ± 0.2 vs. 0.4 ± 0.3 mmHg in controls, mean ± SD, P < 0.0001). The presence of pulmonary hypertension was documented by measuring pulmonary artery pressure by catheterization (22.3 ± 2.3 vs. 16.9 ± 2.7 mmHg, P = 0.0282) and by detecting right ventricular hypertrophy and increased muscularization of peripheral pulmonary vessels. Contributions of a precapillary vascular segment and vasoconstriction to the increased pulmonary vascular resistance were demonstrated, respectively, by arterial occlusion technique and by normalization of resistance by a vasodilator, sodium nitroprusside, in isolated lungs. These changes were comparable, but not additive, to those induced by an established pulmonary hypertension model, chronic hypoxic exposure. Intravascular partial aortic obstruction offers an easy model of pulmonary hypertension induced by left heart disease that has a vasoconstrictor and precapillary component.NEW & NOTEWORTHY We present a new, simple model of a clinically important type of pulmonary hypertension, that induced by left heart failure. Left ventricular pressure overload is induced in rats by inserting a blinded cannula into the ascending aorta via carotid artery access. This partial intravascular aortic obstruction, which does not require opening of the chest and prolonged recovery, causes pulmonary hypertension, which has a precapillary and vasoconstrictor as well as a vascular remodeling component.

Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling.

Down syndrome (DS) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of DS, to quantify heart structure and function with echocardiography in 18-mo male Ts65Dn and wild-type (WT) mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of DS. The left ventricle was smaller in Ts65Dn versus WT, as well as the anterior wall thickness of the left ventricle during both diastole (LVAW_d; mm) and systole (LVAW_s; mm) as assessed by echocardiography. Other functional metrics were similar between groups including left ventricular area end systole (mm2), left ventricular area end diastole (mm2), left ventricular diameter end systole (mm), left ventricular diameter end diastole (mm), isovolumetric relaxation time (ms), mitral valve atrial peak velocity (mm/s), mitral valve early peak velocity (mm/s), ratio of atrial and early peak velocities (E/A), heart rate (beats/min), ejection fraction (%), and fractional shortening (%). Nicotinamide phosphoribosyltransferase (NAMPT) protein expression, NAD concentration, and tissue weight were lower in the left ventricle of Ts65Dn versus WT mice. Sirtuin 3 (SIRT3) protein expression and citrate synthase activity were not different between groups. Although cardiac function was generally preserved in male Ts65Dn, the altered heart size and bioenergetic disturbances may contribute to differences in aging for DS.

Additive effect of admission hyperglycemia on left ventricular stiffness in patients following acute myocardial infarction verified by CMR tissue tracking.

BACKGROUND: Stress hyperglycemia occurs frequently in patients following acute myocardial infarction (AMI) and may aggravate myocardial stiffness, but relevant evidence is still lacking. Accordingly, this study aimed to examine the impact of admission stress hyperglycemia on left ventricular (LV) myocardial deformation in patients following AMI. METHODS: A total of 171 patients with first AMI (96 with normoglycemia and 75 with hyperglycemia) underwent cardiac magnetic resonance (CMR) examination were included. AMI patients were classified according to admission blood glucose level (aBGL): < 7.8 mmol/L (n = 96), 7.8-11.1 mmol/L (n = 41) and ≥ 11.1 mmol/L (n = 34). LV strains, including global radial/circumferential/longitudinal peak strain (PS)/peak systolic strain rate (PSSR)/peak diastolic strain rate (PDSR), were measured and compared between groups. Further, subgroup analyses were separately conducted for AMI patients with and without diabetes. Multivariate analysis was employed to assess the independent association between aBGL and LV global PS in AMI patients. RESULTS: LV global PS, PSSR and PDSR were decreased in radial, circumferential and longitudinal directions in hyperglycemic AMI patients compared with normoglycemic AMI patients (all P < 0.05). These differences were more obvious in patients with diabetes than those without diabetes. AMI patients with aBGL between 7.8 and 11.1 mmol/L demonstrated significant decreased radial and longitudinal PS, radial PSSR, and radial and longitudinal PDSR than those with aBGL < 7.8 mmol/L (all P < 0.05). AMI patients with aBGL ≥ 11.1 mmol/L showed significantly decreased PS, PSSR and PDSR in all three directions than those with aBGL < 7.8 mmol/L, and decreased longitudinal PSSR than those with aBGL between 7.8 and 11.1 (all P < 0.05). Further, aBGL was significantly and independently associated with radial (ß = - 0.166, P = 0.003) and longitudinal (ß = 0.143, P = 0.008) PS. CONCLUSIONS: Hyperglycemia may exacerbate LV myocardial stiffness in patients experienced first AMI, leading to reduction in LV strains. aBGL was an independent indicator of impaired LV global PS in AMI patients. Blood glucose monitoring is more valuable for AMI patients with diabetes.

Assessment of subclinical LV myocardial dysfunction in T2DM patients with diabetic peripheral neuropathy: a cardiovascular magnetic resonance study.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. METHODS: One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. RESULTS: The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: - 15.03 ± 2.52% vs. - 13.39 ± 2.48% vs. - 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (ß = - 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (ß = 0.283 and - 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (ß = - 0.266, p = 0.007). CONCLUSIONS: There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.

Reference Ranges of Ventricular Morphology and Function in Healthy Chinese Adults: A Multicenter 3 T MRI Study.

BACKGROUND: Magnetic resonance imaging (MRI) reference ranges for ventricular morphology and function in the Chinese population are lacking. PURPOSE: To establish the MRI reference ranges of left and right ventricular (LV and RV) morphology and function based on a large multicenter cohort. STUDY TYPE: Prospective. POPULATION: One thousand and twelve healthy Chinese Han adults. FIELD STRENGTH/SEQUENCE: Balanced steady-state free procession cine sequence at 3.0 T. ASSESSMENT: Biventricular end-diastolic, end-systolic, stroke volume, and ejection fraction (EDV, ESV, SV, and EF), LV mass (LVM), end-diastolic and end-systolic dimension (LVEDD and LVESD), anteroseptal wall thickness (AS), and posterolateral wall thickness (PL) were measured. Body surface area (BSA) and height were used to index biventricular parameters. Parameters were compared between age groups and sex. STATISTICAL TESTS: Independent-samples t-tests or Mann-Whitney U test to compare mean values between sexes; ANOVA or Kruskal-Wallis test to compare mean values among age groups; linear regression to assess the relationships between cardiac parameters and age (correlation coefficient, r). A P value <0.05 was considered statistically significant. RESULTS: The biventricular volumes, LVM, LVEDD, RVEDV/LVEDV ratio, LVESD, AS, and PL were significantly greater in males than in females, even after indexing to BSA or height, while LVEF and RVEF were significantly lower in males than in females. For both sexes, age was significantly negatively correlated with biventricular volumes (male and female: LVEDV [r = -0.491; r = -0.373], LVESV [r = -0.194; r = -0.184], RVEDV [r = -0.639; r = -0.506], RVESV [r = -0.270; r = -0.223]), with similar correlations after BSA normalization. LVEF (r = 0.043) and RVEF (r = 0.033) showed a significant correlation with age in females, but not in males (P = 0.889; P = 0.282). DATA CONCLUSION: MRI reference ranges for biventricular morphology and function in Chinese adults are presented and show significant associations with age and sex. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Impact of Type 2 Diabetes Mellitus on Left Atrioventricular Coupling and Left Atrial Deformation in Patients with Essential Hypertension: An MRI Feature Tracking Study.

BACKGROUND: Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are both associated with left ventricular (LV) and left atrial (LA) structural and functional abnormalities; however, the relationship between the left atrium and ventricle in this population is unclear. PURPOSE: To identify differences between hypertensive patients with and without T2DM as the basis for further investigation the atrioventricular coupling relationship. STUDY TYPE: Cross-sectional, retrospective study. POPULATION: 89 hypertensive patients without T2DM [HTN (T2DM-)] (age: 58.4 +/- 11.9 years, 48 male), 62 hypertensive patients with T2DM [HTN (T2DM+)] (age: 58.5 +/- 9.1 years, 32 male) and 70 matched controls (age: 55.0 +/- 9.6 years, 37 male). FIELD STRENGTH/SEQUENCE: 2D balanced steady-state free precession cine sequence at 3.0 T. ASSESSMENT: LA reservoir, conduit, and booster strain (εs, εe, and εa) and strain rate (SRs, SRe, and SRa), LV radial, circumferential and longitudinal peak strain (PS) and peak systolic strain rate and peak diastolic strain rate (PSSR and PDSR) were derived from LA and LV cine images and compared between groups. STATISTICAL TESTS: Chi-square or Fisher's exact test, one-way analysis of variance, analysis of covariance, Pearson's correlation, multivariable linear regression analysis, and intraclass correlation coefficient. A P value <0.05 was considered significant. RESULTS: Compared with controls, εs, εe, SRe and PS-longitudinal, PDSR-radial, and PDSR-longitudinal were significantly lower in HTN (T2DM-) group, and they were even lower in HTN (T2DM+) group than in both controls and HTN (T2DM-) group. SRs, εa, SRa, as well as PS-radial, PS-circumferential, PSSR-radial, and PSSR-circumferential were significantly lower in HTN (T2DM+) compared with controls. Multivariable regression analyses demonstrated that: T2DM and PS-circumferential and PS-longitudinal (ß = -4.026, -0.486, and -0.670, respectively) were significantly associated with εs; T2DM and PDSR-radial and PDSR-circumferential were significantly associated with εe (ß = -3.406, -3.352, and -6.290, respectively); T2DM and PDSR-radial were significantly associated with SRe (ß = 0.371 and 0.270, respectively); T2DM and PDSR-longitudinal were significantly associated with εa (ß = -1.831 and 5.215, respectively); and PDSR-longitudinal was significantly associated with SRa (ß = 1.07). DATA CONCLUSION: In hypertensive patients, there was severer LA dysfunction in those with coexisting T2DM, which may be associated with more severe LV dysfunction and suggests adverse atrioventricular coupling. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

A comparison of fixation and immunofluorescence protocols for successful reproducibility and improved signal in human left ventricle cardiac tissue.

Immunohistochemistry (IHC) and immunofluorescence (IF) are crucial techniques for studying cardiac physiology and disease. The accuracy of these techniques is dependent on various aspects of sample preparation and processing. However, standardised protocols for sample preparation of tissues, particularly for fresh-frozen human left ventricle (LV) tissue, have yet to be established and could potentially lead to differences in staining and interpretation. Thus, this study aimed to optimise the reproducibility and quality of IF staining in fresh-frozen human LV tissue by systematically investigating crucial aspects of the sample preparation process. To achieve this, we subjected fresh-frozen human LV tissue to different fixation protocols, primary antibody incubation temperatures, antibody penetration reagents, and fluorescent probes. We found that neutral buffered formalin fixation reduced image artefacts and improved antibody specificity compared to both methanol and acetone fixation. Additionally, incubating primary antibodies at 37°C for 3 h improved fluorescence intensity compared to the commonly practised 4°C overnight incubation. Furthermore, we found that DeepLabel, an antibody penetration reagent, and smaller probes, such as fragmented antibodies and Affimers, improved the visualisation depth of cardiac structures. DeepLabel also improved antibody penetration in CUBIC cleared thick LV tissue fragments. Thus, our data underscores the importance of standardised protocols in IF staining and provides various means of improving staining quality. In addition to contributing to cardiac research by providing methodologies for IF, the findings and processes presented herein also establish a framework by which staining of other tissues may be optimised.

Deep learning based automated left ventricle segmentation and flow quantification in 4D flow cardiac MRI.

BACKGROUND: 4D flow MRI enables assessment of cardiac function and intra-cardiac blood flow dynamics from a single acquisition. However, due to the poor contrast between the chambers and surrounding tissue, quantitative analysis relies on the segmentation derived from a registered cine MRI acquisition. This requires an additional acquisition and is prone to imperfect spatial and temporal inter-scan alignment. Therefore, in this work we developed and evaluated deep learning-based methods to segment the left ventricle (LV) from 4D flow MRI directly. METHODS: We compared five deep learning-based approaches with different network structures, data pre-processing and feature fusion methods. For the data pre-processing, the 4D flow MRI data was reformatted into a stack of short-axis view slices. Two feature fusion approaches were proposed to integrate the features from magnitude and velocity images. The networks were trained and evaluated on an in-house dataset of 101 subjects with 67,567 2D images and 3030 3D volumes. The performance was evaluated using various metrics including Dice, average surface distance (ASD), end-diastolic volume (EDV), end-systolic volume (ESV), LV ejection fraction (LVEF), LV blood flow kinetic energy (KE) and LV flow components. The Monte Carlo dropout method was used to assess the confidence and to describe the uncertainty area in the segmentation results. RESULTS: Among the five models, the model combining 2D U-Net with late fusion method operating on short-axis reformatted 4D flow volumes achieved the best results with Dice of 84.52% and ASD of 3.14 mm. The best averaged absolute and relative error between manual and automated segmentation for EDV, ESV, LVEF and KE was 19.93 ml (10.39%), 17.38 ml (22.22%), 7.37% (13.93%) and 0.07 mJ (5.61%), respectively. Flow component results derived from automated segmentation showed high correlation and small average error compared to results derived from manual segmentation. CONCLUSIONS: Deep learning-based methods can achieve accurate automated LV segmentation and subsequent quantification of volumetric and hemodynamic LV parameters from 4D flow MRI without requiring an additional cine MRI acquisition.

Aortic stenosis assessment from the 3-chamber cine: Ratio of balanced steady-state-free-precession (bSSFP) blood signal between the aorta and left ventricle predicts severity.

BACKGROUND: Cardiovascular magnetic resonance (CMR) imaging is an important tool for evaluating the severity of aortic stenosis (AS), co-existing aortic disease, and concurrent myocardial abnormalities. Acquiring this additional information requires protocol adaptations and additional scanner time, but is not necessary for the majority of patients who do not have AS. We observed that the relative signal intensity of blood in the ascending aorta on a balanced steady state free precession (bSSFP) 3-chamber cine was often reduced in those with significant aortic stenosis. We investigated whether this effect could be quantified and used to predict AS severity in comparison to existing gold-standard measurements. METHODS: Multi-centre, multi-vendor retrospective analysis of patients with AS undergoing CMR and transthoracic echocardiography (TTE). Blood signal intensity was measured in a ∼1 cm2 region of interest (ROI) in the aorta and left ventricle (LV) in the 3-chamber bSSFP cine. Because signal intensity varied across patients and scanner vendors, a ratio of the mean signal intensity in the aorta ROI to the LV ROI (Ao:LV) was used. This ratio was compared using Pearson correlations against TTE parameters of AS severity: aortic valve peak velocity, mean pressure gradient and the dimensionless index. The study also assessed whether field strength (1.5 T vs. 3 T) and patient characteristics (presence of bicuspid aortic valves (BAV), dilated aortic root and low flow states) altered this signal relationship. RESULTS: 314 patients (median age 69 [IQR 57-77], 64% male) who had undergone both CMR and TTE were studied; 84 had severe AS, 78 had moderate AS, 66 had mild AS and 86 without AS were studied as a comparator group. The median time between CMR and TTE was 12 weeks (IQR 4-26). The Ao:LV ratio at 1.5 T strongly correlated with peak velocity (r = -0.796, p = 0.001), peak gradient (r = -0.772, p = 0.001) and dimensionless index (r = 0.743, p = 0.001). An Ao:LV ratio of < 0.86 was 84% sensitive and 82% specific for detecting AS of any severity and a ratio of 0.58 was 83% sensitive and 92% specific for severe AS. The ability of Ao:LV ratio to predict AS severity remained for patients with bicuspid aortic valves, dilated aortic root or low indexed stroke volume. The relationship between Ao:LV ratio and AS severity was weaker at 3 T. CONCLUSIONS: The Ao:LV ratio, derived from bSSFP 3-chamber cine images, shows a good correlation with existing measures of AS severity. It demonstrates utility at 1.5 T and offers an easily calculable metric that can be used at the time of scanning or automated to identify on an adaptive basis which patients benefit from dedicated imaging to assess which patients should have additional sequences to assess AS.

Impact of an Exercise-Based Cardiac Rehabilitation Program on Cardiopulmonary Test Parameters.

INTRODUCTION: Exercise-based cardiac rehabilitation programs (CRPs) represent a multidisciplinary therapeutic approach tailored to improve cardiorespiratory fitness and overall health-related quality of life, while reducing cardiovascular hospitalizations and mortality. Our aim was to determine changes in exercise capacity and cardiac events according to the left ventricular ejection fraction (LVEF) following a CRP. METHODS: This single-center cohort study included 131 patients who completed a center-based CRP from 2015 to 2022. Cardiopulmonary exercise testing (CPET), transthoracic echocardiography, and laboratory analysis were performed before and after program completion. RESULTS: Of 232 enrolled patients, 131 were included in our cohort analysis, with 36.6% having a reduced LVEF. These patients exhibited higher rates of atrial fibrillation (p = 0.019) and NT-proBNP values (p < 0.001). Patients with reduced LVEF had lower peak VO2 (pVO2) (p = 0.046), percentage of predicted oxygen consumption (ppVO2) (p < 0.001), and VO2 at anaerobic threshold (p = 0.015) during baseline CPET. Completion of the CRP led to comparable improvements in exercise performance between groups, assessed through Δ pVO2 (p = 0.990), Δ ppVO2 (p = 0.610), and Δ VE/VCO2 slope (p = 0.200). In the study population, male gender and hypertension independently predicted variation in VE/VCO2 slope (p = 0.017) and oxygen uptake efficiency slope (p = 0.048), respectively, post-CRP. During follow-up, 9.2% of all patients had hospital admissions for cardiac events, and 3.8% died, with no significant differences between groups. CONCLUSION: Patients with reduced LVEF admitted to our CRP showed lower functional status based on specific CPET parameters. After CRP, both reduced and preserved LVEF groups experienced similar functional improvements. Therefore, strategies to increase participation of patients with reduced LVEF in such programs are warranted.

Are Sodium-Glucose Cotransporter-2 Inhibitors the Cherry on Top of Cardio-Oncology Care?

The increasing aging of the population combined with improvements in cancer detection and care has significantly improved the survival and quality of life of cancer patients. These benefits are hampered by the increase of cardiovascular diseases being heart failure the most frequent manifestation of cardiotoxicity and becoming the major cause of morbidity and mortality among cancer survivor. Current strategies to prevent cardiotoxicity involves different approaches such as optimal management of CV risk factors, use of statins and/or neurohormonal medications, and, in some cases, even the use of chelating agents. As a class, SGLT2-i have revolutionized the therapeutic horizon of HF patients independently of their ejection fraction or glycemic status. There is an abundance of data from translational and observational clinical studies supporting a potential beneficial role of SGLT2-i in mitigating the cardiotoxic effects of cancer patients receiving anthracyclines. These findings underscore the need for more robust clinical trials to investigate the effect on cardiovascular outcomes of the prophylactic SGLT2-i treatment in patients undergoing cancer treatment.

Dapagliflozin, inflammation and left ventricular remodelling in patients with type 2 diabetes and left ventricular hypertrophy.

BACKGROUND AND AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have beneficial effects in heart failure (HF), including reverse remodelling, but the mechanisms by which these benefits are conferred are unclear. Inflammation is implicated in the pathophysiology of heart failure (HF) and there are some pre-clinical data suggesting that SGLT2 inhibitors may reduce inflammation. There is however a lack of clinical data. The aim of our study was to investigate whether improvements in cardiac remodelling caused by dapagliflozin in individuals with type 2 diabetes (T2D) and left ventricular hypertrophy (LVH) were associated with its effects on inflammation. METHODS: We measured C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), interleukin 6 (IL-6), and interleukin 10 (IL-10) and neutrophil-to-lymphocyte ratio (NLR) in plasma samples of 60 patients with T2D and left ventricular hypertrophy (LVH) but without symptomatic HF from the DAPA-LVH trial in which participants were randomised dapagliflozin 10 mg daily or placebo for 12 months and underwent cardiac magnetic resonance imaging (CMR) at baseline and end of treatment. The primary analysis was to investigate the effect of dapagliflozin on inflammation and to assess the relationships between changes in inflammatory markers and LV mass and global longitudinal strain (GLS) and whether the effect of dapagliflozin on LV mass and GLS was modulated by baseline levels of inflammation. RESULTS: Following 12 months of treatment dapagliflozin significantly reduced CRP compared to placebo (mean difference of -1.96; 95% CI -3.68 to -0.24, p = 0.026). There were no significant statistical changes in other inflammatory markers. There were modest correlations between improvements in GLS and reduced inflammation (NLR (r = 0.311), IL-1ß (r = 0.246), TNF-α (r = 0.230)) at 12 months. CONCLUSIONS: Dapagliflozin caused a significant reduction in CRP compared to placebo. There were correlations between reductions in inflammatory markers including IL-1ß and improvements in global longitudinal strain (but not reduced LV mass). Reductions in systemic inflammation might play a contributory role in the cardiovascular benefits of dapagliflozin. TRIAL REGISTRATION: Clinicaltrials.gov NCT02956811 (06/11/2016).

Inadvertent misplacement of pacemaker lead presented with acute ischemic stroke.

If a permanent pacemaker lead is misplaced in the left ventricle (LV), the lead may interfere with normal functioning of the heart leading various complications, including heart rhythm problems and blood clots. In our case, the LV lead that passed through the patent foramen ovale and was misplaced into the LV was detected in a 78-year-old patient who presented with embolic stroke. Thrombus regression was achieved with anticoagulation, and then the lead extraction was planned. The lead extraction is a priority in acute cases; but it is not the primary approach in long-term leads that were misplaced into the LV. A patient-based individual approach should be preferred in such cases.

Simulating impaired left ventricular-arterial coupling in aging and disease: a systematic review.

Aortic stenosis, hypertension, and left ventricular hypertrophy often coexist in the elderly, causing a detrimental mismatch in coupling between the heart and vasculature known as ventricular-vascular (VA) coupling. Impaired left VA coupling, a critical aspect of cardiovascular dysfunction in aging and disease, poses significant challenges for optimal cardiovascular performance. This systematic review aims to assess the impact of simulating and studying this coupling through computational models. By conducting a comprehensive analysis of 34 relevant articles obtained from esteemed databases such as Web of Science, Scopus, and PubMed until July 14, 2022, we explore various modeling techniques and simulation approaches employed to unravel the complex mechanisms underlying this impairment. Our review highlights the essential role of computational models in providing detailed insights beyond clinical observations, enabling a deeper understanding of the cardiovascular system. By elucidating the existing models of the heart (3D, 2D, and 0D), cardiac valves, and blood vessels (3D, 1D, and 0D), as well as discussing mechanical boundary conditions, model parameterization and validation, coupling approaches, computer resources and diverse applications, we establish a comprehensive overview of the field. The descriptions as well as the pros and cons on the choices of different dimensionality in heart, valve, and circulation are provided. Crucially, we emphasize the significance of evaluating heart-vessel interaction in pathological conditions and propose future research directions, such as the development of fully coupled personalized multidimensional models, integration of deep learning techniques, and comprehensive assessment of confounding effects on biomarkers.

Estimate of the hydraulic force in the aging heart: a cardiovascular magnetic resonance imaging study.

BACKGROUND: Coupling between left ventricle (LV) and left atrium (LA) plays a central role in the process of cardiac remodeling during aging and development of cardiac disease. The hydraulic force (HyF) is related to variation in size between LV and LA. The objectives of this study were to: (1) derive an estimate of left atrioventricular HyF using cine- Magnetic Resonance Imaging (MRI) in healthy subjects with a wide age range, and (2) study its relationship with age and conventional diastolic function parameters, as estimated by reference echocardiography. METHODS: We studied 119 healthy volunteers (mean age 44 ± 17 years, 58 women) who underwent Doppler echocardiography and MRI on the same day. Conventional transmitral flow early (E) and late (A) LV filling peak velocities as well as mitral annulus diastolic longitudinal peak velocity (E') were derived from echocardiography. MRI cine SSFP images in longitudinal two and four chamber views were acquired, and analyzed using feature tracking (FT) software. In addition to conventional LV and LA strain measurements, FT-derived LV and LA contours were further used to calculate chamber cross-sectional areas. HyF was approximated as the difference between the LV and LA maximal cross-sectional areas in the diastasis phase corresponding to the lowest LV-LA pressure gradient. Univariate and multivariate analyses while adjusting for appropriate variables were used to study the associations between HyF and age as well as diastolic function and strain indices. RESULTS: HyF decreased significantly with age (R²=0.34, p < 0.0001). In addition, HyF was significantly associated with conventional indices of diastolic function and LA strain: E/A: R²=0.24, p < 0.0001; E': R²=0.24, p < 0.0001; E/E': R²=0.12, p = 0.0004; LA conduit longitudinal strain: R²=0.27, p < 0.0001. In multivariate analysis, associations with E/A (R2 = 0.39, p = 0.03) and LA conduit strain (R2 = 0.37, p = 0.02) remained significant after adjustment for age, sex, and body mass index. CONCLUSIONS: HyF, estimated using FT contours, which are primarily used to quantify LV/LA strain on standard cardiac cine MRI, varied significantly with age in association with subclinical changes in ventricular filling. Its usefulness in cohorts of patients with left heart disease to detect LV-LA uncoupling remains to be evaluated.

The effect of long-term soccer training on left ventricular structure and function in elite male youth soccer players.

AIMS: Cardiac adaptations in elite, male adolescent youth soccer players have been demonstrated in relation to training status. The time course of these adaptations and the delineation of the influence of volatile growth phases from the training effect on these adaptations remain unclear. Consequently, the aims of the study were to evaluate the impact of 3 years of elite-level soccer training on changes in left ventricular (LV) structure and function in a group of highly trained elite youth male soccer players (SP) as they transitioned through the pre-to-adolescent phase of their growth. METHODS: Twenty-two male youth SP from the highest Level of English Premier League Academy U-12 teams were evaluated once a year for three soccer seasons as the players progressed from the U-12 to U-14 teams. Fifteen recreationally active control participants (CON) were also evaluated over the same 3-year period. Two-dimensional transthoracic echocardiography was used to quantify LV structure and function. RESULTS: After adjusting for the influence of growth and maturation, training-induced increases in Years 2 and 3 were noted for: LV end diastolic volume (LVEDV; p = 0.02) and LV end systolic volume (LVESV; p = 0.02) in the SP compared to CON. Training-induced decrements were noted for LV ejection fraction (LVEF; p = 0.006) and TDI-S' (p < 0.001). CONCLUSIONS: An increase in training volume (Years 2 and 3) were aligned with LV volumetric adaptations and decrements in systolic function in the SP that were independent from the influence of rapid somatic growth. Decrements in systolic function were suggestive of a functional reserve for exercise.

Imaging of Double Inlet Left Ventricle.

Double inlet left ventricle (DILV) is a form of single ventricle heart disease where both atrioventricular valves enter a single left ventricle. Surgical intervention may be needed in the neonatal period secondary to systemic outflow tract obstruction or less commonly pulmonary obstruction. Two-dimensional echocardiography can adequately assess newborn anatomy and define the need for surgery. Beyond the newborn period, there is a renewed interest in septation of DILV using intracardiac baffles in a staged approach. Cross sectional imaging can aid in surgical planning. This article will review common anatomic features of DILV and imaging considerations for both single ventricle palliation and DILV septation.

Staged Ventricular Septation of the Double-Inlet Ventricle: How-I-Do-It.

Ventricular septation of the double-inlet ventricle is a largely abandoned operation due to poor historical outcomes. However, there has been renewed interest in septation as an alternative to Fontan palliation given its long-term sequelae. As one of the few centers to revisit septation in the early 1990s, our institution has long-term data on a series of patients with a double-inlet ventricle who underwent biventricular repair. This manuscript is a summary of our approach to staged septation of the double-inlet ventricle, with a focus on patient selection criteria, surgical techniques, perioperative considerations on timing of interventions, and long-term results. We believe that septation of the double-inlet ventricle should be reconsidered in patients with suitable anatomy in light of the known complications of Fontan palliation.

The reduction of the left ventricular long-axis early diastolic peak velocity (e') evident by early-middle age occurs in the absence of aging-related slowing of active relaxation.

PURPOSE: A decrease in the left ventricular (LV) long-axis early diastolic peak velocity (e') is evident by early-middle age, but it is unknown to what extent this decrease is due to slowing of the speed of active relaxation versus a reduction in LV long-axis excursion during early diastole (EDExc). METHODS: Pulsed-wave tissue Doppler imaging (TDI) signals were acquired from the septal and lateral borders of the mitral annulus in 62 healthy adult subjects of age 18-45 years. EDExc and LV systolic excursion (SExc) were measured as the integrals of the respective TDI signals. The speed of active relaxation was indirectly assessed using time interval measurements related to the TDI early diastolic signal, including the isovolumic relaxation time (IVRT'), the acceleration time (EDAT), and the duration (EDDur). Multiple linear regression analyses were performed to identify the relationships between e', age, EDExc, SExc, and time intervals. RESULTS: The findings were similar for both LV walls. Age was negatively correlated with e' and EDExc, but was not correlated with SExc, IVRT', EDAT, or EDDur. The closest correlate of EDExc was SExc, and EDExc was independently correlated with both SExc and age. e' was also positively correlated with SExc, but the closest correlate of e' was EDExc, and when combined with EDExc, EDDur became an independent predictor of e'. CONCLUSION: The aging-related decrease in e' evident by early-middle age occurs in the absence of aging-related slowing of active relaxation and therefore can be largely attributed to the accompanying reduction in EDExc.