Radiological assessment of effectiveness of soluble RAGE in attenuating Angiotensin II-induced LVH mouse model using in vivo 9.4T MRI.
ABSTRACT: We investigated the effectiveness of soluble Receptor for Advanced Glycation Endproducts (sRAGE) in attenuating angiotensin II (AngII)-induced left ventricular hypertrophy (LVH) using in vivo 9.4T cine-magnetic resonance imaging (CINE-MRI). Mice were divided into four groups: AngII (n = 9), saline (n = 10), sRAGE (n = 10), and AngII + sRAGE (n = 10). CINE-MRI was performed in each group after administration of the AngII or sRAGE, and CINE-MR images were analyzed to obtain parameters indicating cardiac anatomical and functional changes including end-diastolic and end-systolic blood volume, end-diastolic and end-systolic myocardial volume, ejection fraction, end-diastolic and end-systolic myocardial mass, and LV wall thickness. LVH observed in AngII group was significantly attenuated by sRAGE. These trends were also observed in histological analysis, demonstrating that cardiac function tracking using in vivo and real-time 9.4T MR imaging provides valuable information about the cardiac remodeling induced by AngII and sRAGE in an AngII-induced LV hypertrophy mice model.
Project description:Although concentric remodeling (CR) and concentric hypertrophy (CH) are common forms of left ventricular (LV) remodeling in heart failure with preserved ejection fraction (HFpEF), eccentric hypertrophy (EH) can also occur in these patients. However, clinical characteristics and outcomes of EH have not been well described in HFpEF. We prospectively studied 402 patients with HFpEF, divided into 4 groups based on LV structure: normal geometry (no LV hypertrophy [LVH] and relative wall thickness [RWT] ≤0.42); CR (no LVH and RWT >0.42); CH (LVH and RWT >0.42); and EH (LVH and RWT ≤0.42). We compared clinical, laboratory, echocardiographic, invasive hemodynamic, and outcome data among groups. Of 402 patients, 48 (12%) had EH. Compared with CH, patients with EH had lower systolic blood pressure and less renal impairment despite similar rates of hypertension. After adjustment for covariates, EH was associated with reduced LV contractility compared with CH: lower LVEF (β coefficient = -3.2; 95% confidence interval [CI] -5.4 to -1.1%) and ratio of systolic blood pressure to end-systolic volume (β coefficient = -1.0; 95% CI -1.5 to -0.5 mm Hg/ml). EH was also associated with increased LV compliance compared with CH (LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mm Hg β coefficient = 14.2; 95% CI 9.4 to 19.1 ml). Despite these differences, EH and CH had similarly elevated cardiac filling pressures and equivalent adverse outcomes. In conclusion, the presence of EH denotes a distinct subset of HFpEF that is pathophysiologically similar to HF with reduced EF (HFrEF) and may benefit from HFrEF therapy.
Project description:Importance:Sarcomere mutations and left ventricular (LV) hypertrophy (LVH) are cardinal features of hypertrophic cardiomyopathy (HCM). However, little is known about the full spectrum of phenotypic manifestations or how LVH influences disease expression. Objectives:(1) To characterize and assess phenotypic burden in sarcomere mutation carriers (genotype positive [G+]) and (2) to investigate the correlation between LV wall thickness (LVWT) and other disease features in mutation carriers. Design, Setting, and Participants:This investigation was a cross-sectional, multicenter observational study in the setting of the HCMNet network of HCM clinical centers. Mutation carriers with LVH (G+/LVH+), mutation carriers without LVH (G+/LVH-), and healthy related control individuals (G-/LVH-) were enrolled through HCMNet sites. A total of 193 participants were enrolled and underwent study procedures. Participants were enrolled between April 9, 2010, and January 30, 2012. Study analysis was performed between June 2015 and May 2016. Exposures:The primary stratifying variables were the presence of a sarcomere mutation and measures of LVWT. Main Outcomes and Measures:Variables from standardized exercise testing, echocardiography, cardiac magnetic resonance imaging, serum biomarker measurement, and electrocardiography were compared across study cohorts. Results:Analyses were performed in 178 participants, including 81 G+/LVH+ (mean [SD] age at baseline, 27  years), 55 G+/LVH- (20  years), and 42 G-/LVH- (18  years). All mutation carriers had smaller LV cavity, higher ratio of LVWT to diastolic diameter, and higher echocardiographic LV ejection fraction than controls. A phenotypic burden score was evaluated as the cumulative number of 7 traits (changes on electrocardiography; decreased LV systolic, diastolic diameter, or septal E' velocity; higher ratio of LVWT to diastolic diameter; serum troponin level; and natriuretic peptide level) in each individual. The mean (SE) phenotypic burden was 4.9 (0.2) phenotypes per individual in G+/LVH+, 2.4 (0.2) in G+/LVH-, and 1.3 (0.2) in controls (P?<?.001). Classification and regression tree analysis identified an LV end-diastolic dimension z score less than -1.85 or the combination of an LV end-diastolic dimension z score of -1.85 or higher and a septal E' velocity z score less than -0.52 as having 74% accuracy in discriminating G+/LVH- participants from controls. In mutation carriers, clinical variables demonstrated a continuous correlation with LVWT, generally without a clear cutoff signifying pathologic transition. Conclusions and Relevance:G+/LVH- individuals demonstrated altered cardiac dimensions and function and a higher burden of early phenotypes than healthy G- controls. Two methods discriminated phenotypic subgroups, namely, a sum across 7 traits and a regression tree-based rule that identifies constellations of distinguishing factors. Greater LVWT is associated with more prominent cardiac abnormalities in a continuous, although not always linear, manner. A single value of LVWT could not dichotomize the presence or absence of disease.
Project description:Cardiac CINE magnetic resonance imaging is the gold-standard for the assessment of cardiac function. Imaging accelerations have shown to enable 3D CINE with left ventricular (LV) coverage in a single breath-hold. However, 3D imaging remains limited to anisotropic resolution and long reconstruction times. Recently deep learning has shown promising results for computationally efficient reconstructions of highly accelerated 2D CINE imaging. In this work, we propose a novel 4D (3D?+?time) deep learning-based reconstruction network, termed 4D CINENet, for prospectively undersampled 3D Cartesian CINE imaging. CINENet is based on (3?+?1)D complex-valued spatio-temporal convolutions and multi-coil data processing. We trained and evaluated the proposed CINENet on in-house acquired 3D CINE data of 20 healthy subjects and 15 patients with suspected cardiovascular disease. The proposed CINENet network outperforms iterative reconstructions in visual image quality and contrast (+?67% improvement). We found good agreement in LV function (bias?±?95% confidence) in terms of end-systolic volume (0?±?3.3 ml), end-diastolic volume (-?0.4?±?2.0 ml) and ejection fraction (0.1?±?3.2%) compared to clinical gold-standard 2D CINE, enabling single breath-hold isotropic 3D CINE in less than 10 s scan and?~?5 s reconstruction time.
Project description:BACKGROUND: Connective tissue growth factor (CTGF) has been implicated in the cardiac and kidney complications of type 2 diabetes, and the CTGF -945 G/C polymorphism is associated with susceptibility to systemic sclerosis, a disease characterised by tissue fibrosis. This study investigated the association of the CTGF -945 G/C promoter variant with cardiac complications (left ventricular (LV) hypertrophy (LVH), diastolic and systolic dysfunction) and chronic kidney disease (CKD) in type 2 diabetes. METHODS: The CTGF -945 G/C polymorphism (rs6918698) was examined in 495 Caucasian subjects with type 2 diabetes. Cardiac structure and function were assessed by transthoracic echocardiography. Kidney function was assessed using estimated glomerular filtration rate (eGFR) and albuminuria, and CKD defined as the presence of kidney damage (decreased kidney function (eGFR <60 ml/min/1.73 m2) or albuminuria). RESULTS: The mean age ± SD of the cohort was 62 ± 14 years, with a body mass index (BMI) of 31 ± 6 kg/m2 and median diabetes duration of 11 years [25th, 75th interquartile range; 5, 18]. An abnormal echocardiogram was present in 73% of subjects; of these, 8% had LVH alone, 74% had diastolic dysfunction and 18% had systolic ± diastolic dysfunction. CKD was present in 42% of subjects. There were no significant associations between the CTGF -945 G/C polymorphism and echocardiographic parameters of LV mass or cardiac function, or kidney function both before and after adjustment for covariates of age, gender, BMI, blood pressure and hypertension. CTGF -945 genotypes were not associated with the cardiac complications of LVH, diastolic or systolic dysfunction, nor with CKD. CONCLUSIONS: In Caucasians with type 2 diabetes, genetic variation in the CTGF -945 G/C polymorphism is not associated with cardiac or kidney complications.
Project description:OBJECTIVES:To evaluate the effect of different ranges of systolic blood pressure (SBP) on left ventricular (LV) geometry and diastolic function in Chinese population. DESIGN:Cross-sectional study. SETTING:Peking Union Medical College Hospital in Beijing, China. PARTICIPANTS:All inhabitants aged 35 years or older, living in five villages of Shunyi were invited. Exclusion criteria included individuals who declined participation, presence of moderate to severe valvular heart disease, persistent atrial fibrillation and suboptimal echocardiograms. INTERVENTIONS:The baseline data of 1051 participants were analysed. The relationship between SBP and LV geometric and diastolic function assessed by echocardiography was analysed after adjusting for conventional cardiac risk factors. RESULTS:The adjusted value of SBP was independently associated with LV hypertrophy (LVH) and LV diastolic dysfunction (LVDDF) (all p<0.01). Setting individuals with SBP <120 mm Hg as the reference group (group 1), those with SBP between 120 mm Hg and 140 mm Hg (group 2) had higher risk odds of LVH and those with SBP ≥140 mm Hg (group 3) had higher risk odds of LVH and LVDDF (all p<0.01). With the increase of SBP, LV mass index (LVMI) and E/e' stepwise increased and e' stepwise decreased significantly from group 1 to 3 (all p<0.05). In the whole population, SBP was independently correlated with LVMI, LVEDD, Left Atrial Volume Index, e', and E/e' (all p<0.01). CONCLUSIONS:SBP was independently related to LVH and LVDDF, SBP between 120 and 140 mm Hg was independently related to worse LV remodelling and diastolic function, these findings indicated the potential benefit of intensive SBP control.
Project description:Heart failure (HF) is a frequent occurrence in chronic kidney disease (CKD) patients and predicts poor survival. Serum bicarbonate is associated with increased rates of HF in CKD; however, the mechanisms leading to this association are incompletely understood. This study aims to assess whether serum bicarbonate is independently associated with structural and functional cardiac abnormalities in CKD.The association between serum bicarbonate and left ventricular (LV) hypertrophy (LVH), LV mass indexed to height2.7, LV geometry, ejection fraction (EF) and diastolic dysfunction was assessed in 3,483 participants without NYHA class III/IV HF, enrolled in the Chronic Renal Insufficiency Cohort study.The mean estimated glomerular filtration rate was 42.5 ± 17 ml/min/1.73 m2. The overall prevalence of LVH was 51.2%, with 57.8, 50.9 and 47.7% for bicarbonate categories <22, 22-26 and >26 mmol/l, respectively. Participants with low bicarbonate were more likely to have LVH and abnormal LV geometry (OR 1.32; 95% CI 1.07-1.64, and OR 1.57; 95% CI 1.14-2.16, respectively). However, the association was not statistically significant after adjustment for demographics, traditional cardiovascular risk factors, medications and kidney function (OR 1.07; 95% CI 0.66-1.72, and OR 1.27; 95% CI 0.64-2.51, respectively). No association was found between bicarbonate and systolic or diastolic dysfunction. During follow-up, no significant changes in LV mass or EF were observed in any bicarbonate strata.In a large CKD study, serum bicarbonate was associated with LV mass and concentric LVH; however, this association was attenuated after adjustment for clinical factors suggesting that the observed cardiac effects are mediated through yet unknown mechanisms.
Project description:Heart failure is a common consequence of CKD, and it portends high risk for mortality. However, among patients without known heart failure, the associations of different stages of estimated GFR (eGFR) with changes in cardiac structure and function are not well described. Here, we performed a cross-sectional analysis to study these associations among 3487 participants of the Chronic Renal Insufficiency Cohort Study. We estimated GFR using cystatin C. The prevalence of left ventricular hypertrophy (LVH) assessed by echocardiography was 32%, 48%, 57%, and 75% for eGFR categories ?60, 45-59, 30-44, and <30 ml/min per 1.73 m(2), respectively. In fully adjusted multivariable analyses, subjects with eGFR levels of <30 ml/min per 1.73 m(2) had twofold higher odds of LVH (OR=2.20, 95% CI=1.40-3.40; P<0.001) relative to subjects with eGFR?60 ml/min per 1.73 m(2). This reduction in kidney function also significantly associated with abnormal LV geometry but not diastolic or systolic dysfunction. An eGFR of 30-44 ml/min per 1.73 m(2) also significantly associated with LVH and abnormal LV geometry compared with eGFR?60 ml/min per 1.73 m(2). In summary, in this large CKD cohort, reduced kidney function associated with abnormal cardiac structure. We did not detect significant associations between kidney function and systolic or diastolic function after adjusting for potential confounding variables.
Project description:The goal of this study was to assess the relationship among extracellular volume (ECV), native T1, and systolic strain in hypertensive patients with left ventricular hypertrophy (HTN LVH), hypertensive patients without LVH (HTN non-LVH), and normotensive controls.Diffuse myocardial fibrosis in HTN LVH patients, as reflected by increased ECV and native T1, may be an underlying mechanism contributing to increased cardiovascular risk compared with HTN non-LVH subjects and controls. Furthermore, increased diffuse fibrosis in HTN LVH subjects may be associated with reduced peak systolic and early diastolic strain rate compared with the other 2 groups.T1 mapping was performed in 20 HTN LVH (mean age, 55 ± 11 years), 23 HTN non-LVH (mean age, 61 ± 12 years), and 22 control subjects (mean age, 54 ± 7 years) on a Siemens 1.5-T Avanto (Siemens Healthcare, Erlangen, Germany) using a previously validated modified look-locker inversion-recovery pulse sequence. T1 was measured pre-contrast and 10, 15, and 20 min after injection of 0.15 mmol/kg gadopentetate dimeglumine, and the mean ECV and native T1 were determined for each subject. Measurement of circumferential strain parameters were performed using cine displacement encoding with stimulated echoes.HTN LVH subjects had higher native T1 compared with controls (p < 0.05). HTN LVH subjects had higher ECV compared with HTN non-LVH subjects and controls (p < 0.05). Peak systolic circumferential strain and early diastolic strain rates were reduced in HTN LVH subjects compared with HTN non-LVH subjects and controls (p < 0.05). Increased levels of ECV and native T1 were associated with reduced peak systolic and early diastolic circumferential strain rate across all subjects.HTN LVH patients had higher ECV, longer native T1 and associated reduction in peak systolic circumferential strain, and early diastolic strain rate compared with HTN non-LVH and control subjects. Measurement of ECV and native T1 provide a noninvasive assessment of diffuse fibrosis in hypertensive heart disease.
Project description:OBJECTIVES: To compare Magnetic Resonance (MR) and Computed Tomography (CT) for the assessment of left (LV) and right (RV) ventricular functional parameters. METHODS: Seventy nine patients underwent both Cardiac CT and Cardiac MR. Images were acquired using short axis (SAX) reconstructions for CT and 2D cine b-SSFP (balanced-steady state free precession) SAX sequence for MR, and evaluated using dedicated software. RESULTS: CT and MR images showed good agreement: LV EF (Ejection Fraction) (52 ?± ?14% for CT vs. 52? ± ?14% for MR; r? =? 0.73; p ?> ?0.05); RV EF (47 ?±? 12% for CT vs. 47?±?12% for MR; r ?= ?0.74; p?>?0.05); LV EDV (End Diastolic Volume) (74? ± ?21 ml/m² for CT vs. 76? ±? 25 ml/m² for MR; r? =? 0.59; p?>?0.05); RV EDV (84? ± ?25 ml/m² for CT vs. 80 ?±? 23 ml/m² for MR; r? =? 0.58; p?>?0.05); LV ESV (End Systolic Volume)(37? ± ?19 ml/m² for CT vs. 38 ?±? 23 ml/m² for MR; r ?= ?0.76; p ?> ?0.05); RV ESV (46? ± ?21 ml/m² for CT vs. 43 ?±? 18 ml/m² for MR; r? = ?0.70; p ?>? 0.05). Intra- and inter-observer variability were good, and the performance of CT was maintained for different EF subgroups. CONCLUSIONS: Cardiac CT provides accurate and reproducible LV and RV volume parameters compared with MR, and can be considered as a reliable alternative for patients who are not suitable to undergo MR. KEY POINTS: • Cardiac-CT is able to provide Left and Right Ventricular function. • Cardiac-CT is accurate as MR for LV and RV volume assessment. • Cardiac-CT can provide accurate evaluation of coronary arteries and LV and RV function.
Project description:Cardiac magnetic resonance (MR) imaging is one of the most rigorous form of imaging to assess cardiac function in vivo. Strain analysis allows comprehensive assessment of diastolic myocardial function, which is not indicated by measuring systolic functional parameters using with a normal cine imaging module. Due to the small heart size in mice, it is not possible to perform proper tagged imaging to assess strain. Here, we developed a novel deep learning approach for automated quantification of strain from cardiac cine MR images. Our framework starts by an accurate localization of the LV blood pool center-point using a fully convolutional neural network (FCN) architecture. Then, a region of interest (ROI) that contains the LV is extracted from all heart sections. The extracted ROIs are used for the segmentation of the LV cavity and myocardium via a novel FCN architecture. For strain analysis, we developed a Laplace-based approach to track the LV wall points by solving the Laplace equation between the LV contours of each two successive image frames over the cardiac cycle. Following tracking, the strain estimation is performed using the Lagrangian-based approach. This new automated system for strain analysis was validated by comparing the outcome of these analysis with the tagged MR images from the same mice. There were no significant differences between the strain data obtained from our algorithm using cine compared to tagged MR imaging. Furthermore, we demonstrated that our new algorithm can determine the strain differences between normal and diseased hearts.