Differentiating Left Ventricular Remodeling in Aortic Stenosis From Systemic Hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy occurs in both aortic stenosis (AS) and systemic hypertension (HTN) in response to wall stress. However, differentiation of hypertrophy due to these 2 etiologies is lacking. The aim was to study the 3-dimensional geometric remodeling pattern in severe AS pre- and postsurgical aortic valve replacement and to compare with HTN and healthy controls. METHODS: Ninety-one subjects (36 severe AS, 19 HTN, and 36 healthy controls) underwent cine cardiac magnetic resonance. Cardiac magnetic resonance was repeated 8 months post-aortic valve replacement (n=18). Principal component analysis was performed on the 3-dimensional meshes reconstructed from 109 cardiac magnetic resonance scans of 91 subjects at end-diastole. Principal component analysis modes were compared across experimental groups together with conventional metrics of shape, strain, and scar. RESULTS: A unique AS signature was identified by wall thickness linked to a LV left-right axis shift and a decrease in short-axis eccentricity. HTN was uniquely linked to increased septal thickness. Combining these 3 features had good discriminative ability between AS and HTN (area under the curve, 0.792). The LV left-right axis shift was not reversible post-aortic valve replacement, did not associate with strain, age, or sex, and was predictive of postoperative LV mass regression (R2=0.339, P=0.014). CONCLUSIONS: Unique remodeling signatures might differentiate the etiology of LV hypertrophy. Preliminary findings suggest that LV axis shift is characteristic in AS, is not reversible post-aortic valve replacement, predicts mass regression, and may be interpreted to be an adaptive mechanism.

Echocardiographic Strain Abnormalities Precede Left Ventricular Hypertrophy Development in Hypertrophic Cardiomyopathy Mutation Carriers.

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and increased sudden-death risk. Early detection of the phenotypic expression of the disease in genetic carriers without LVH (Gen+/Phen-) is crucial for emerging therapies. This clinical study aims to identify echocardiographic predictors of phenotypic development in Gen+/Phen-. Sixteen Gen+/Phen- (one subject with troponin T, six with myosin heavy chain-7, and nine with myosin-binding protein C3 mutations), represented the study population. At first and last visit we performed comprehensive 2D speckle-tracking strain echocardiography. During a follow-up of 8 ± 5 years, five carriers developed LVH (LVH+). At baseline, these patients were older than those who did not develop LVH (LVH-) (30 ± 8 vs. 15 ± 8 years, p = 0.005). LVH+ had reduced peak global strain rate during the isovolumic relaxation period (SRIVR) (0.28 ± 0.05 vs. 0.40 ± 0.11 1/s, p = 0.048) and lower global longitudinal strain (GLS) (-19.8 ± 0.4 vs. -22.3 ± 1.1%; p < 0.0001) than LVH- at baseline. SRIVR and GLS were not correlated with age (overall, p > 0.08). This is the first HCM study investigating subjects before they manifest clinically significant or relevant disease burden or symptomatology, comparing at baseline HCM Gen+/Phen- subjects who will develop LVH with those who will not. Furthermore, we identified highly sensitive, easily obtainable, age- and load-independent echocardiographic predictors of phenotype development in HCM gene carriers who may undergo early preventive treatment.

Association between serum ß2-microglobulin and left ventricular hypertrophy in patients with type 2 diabetes mellitus: A cross-sectional study.

BACKGROUND: Beta 2-microglobulin (ß2-MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of ß2-MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum ß2-MG and LVH in T2DM patients. METHODS: The retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non-LVH groups based on echocardiography results. Serum ß2-MG levels were measured, and participants were categorized into four groups (Q1-Q4) by their serum ß2-MG quartile. The relationship of serum ß2-MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning. RESULTS: The prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum ß2-MG level corresponded to a 1.17-fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05-1.31); p = 0.006]. When considering ß2-MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09-1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36-2.31); p < 0.001] had a significantly higher prevalence of LVH than Q1. RCS analysis found a nonlinear association between ß2-MG and LVH prevalence (p for nonlinearity <0.05). Additionally, machine learning results confirmed the importance of ß2-MG for LVH in T2DM patients. CONCLUSION: Elevated serum ß2-MG levels were likely to be associated with an increased prevalence of LVH in T2DM patients, suggesting its potential role in LVH development.

Effect of henagliflozin on left ventricular mass index in dialysis patients with HFpEF (HELD-HF): protocol for a multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a prevalent comorbidity among patients with end-stage kidney disease. Although sodium-glucose cotransporter 2 inhibitors are validated in treating heart failure and ameliorating left ventricular hypertrophy among non-dialysis patients, the effects on dialysis patients are unknown. We previously investigated the pharmacokinetics of henagliflozin in patients undergoing haemodialysis (HD) or peritoneal dialysis (PD) and clarified its safety. METHODS AND ANALYSIS: This multicentre, randomised, double-blind, placebo-controlled trial is being conducted at three hospitals in Shanghai, China. A target of 108 HD or PD patients with HFpEF are randomly allocated to treatment group (henagliflozin 5 mg/day in addition to standard therapy) or control group (placebo with standard therapy) at a ratio of 1:1. All subjects will be followed up for 24 weeks. The primary outcome is change in echocardiography-measured left ventricular mass index. The secondary interests include changes in left atrial volume index, E/e', e' and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Intergroup comparisons of change in echocardiography-related outcomes from baseline to 24 weeks are based on a linear regression model adjusted for baseline values (analysis of covariance), and repeated measure analysis of variance with Bonferroni adjustment is employed for comparison of change in NT-proBNP. Subgroup analyses of the primary and secondary outcomes are conducted to determine whether the effect of henagliflozin varies according to dialysis modality. The χ2 method is used to compare the occurrence of adverse events and severe adverse events. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University (LY2023-127-B). All participants provide written informed consent before screening. The results of the trial will be disclosed completely in international peer-reviewed journals. Both positive and negative results will be reported. TRIAL REGISTRATION NUMBER: ChiCTR2300073169.

Serum parathormone, vitamin D and cardiovascular risk factors and markers: A pilot study.

BACKGROUND AND AIMS: Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. The aim of this study was to evaluate the associations of serum vitamin D and parathormone (PTH) concentrations with blood pressure values and hypertension-mediated target organ damage (HMOD), including left ventricular (LV) hypertrophy and carotid plaque (CP). METHODS AND RESULTS: We enrolled consecutive patients admitted to the Hypertension Center of Federico II University Hospital in Naples, Italy. All patients underwent carotid doppler ultrasound and echocardiography, measurement of vitamin D and PTH levels and main clinical and laboratory parameters. A total of 126 patients (mean age 54 years, 68% males) were enrolled. Pearson's correlation analysis indicated that PTH levels directly correlated with age, diabetes, dyslipidemia, hypertension, fasting glucose, and LV mass, and inversely with glomerular filtration rate, LDL cholesterol, and vitamin D. Vitamin D levels correlated inversely with PTH, diabetes and CP. Multivariate regression models indicated that an increased LV mass was associated with the presence of obesity (ß = 0.342; P = 0.001). Maximal intima-media thickness was significantly associated with older age (ß = 0.303; P = 0.033). Combined presence of low vitamin D/high PTH levels were associated with more than 4-fold increased risk of having CP in both univariate (OR = 4.77, p = 0.0001) and multivariate regression analysis (OR = 4.52, p = 0.014). CONCLUSION: In a population at high cardiovascular risk, vitamin D and PTH levels were not directly associated with blood pressure values and HMOD. Secondary hyperparathyroidism due to vitamin D deficiency is associated with carotid atherosclerosis independently of other common cardiovascular risk factors.

Impact of volume indices in bioelectrical impedance measurement on the assessment of cardiac function indices by echocardiography in hemodialysis patients.

INTRODUCTION: Cardiovascular events resulting from volume overload are a primary cause of mortality in hemodialysis patients. Bioelectrical impedance analysis (BIA) is significantly valuable for assessing the volume status of hemodialysis (HD) patients. In this article, we explore the correlation between the volume index measured by BIA and the cardiac function index assessed by echocardiography (ECG) in HD patients. METHODS: Between April and November 2018, we conducted a cross-sectional study involving randomly selected 126 maintenance HD patients. Comprehensive data on medical history and laboratory test results were collected. Subsequently, we investigated the correlation between volume indices measured by BIA and cardiac function parameters by ECG. RESULTS: We discovered a significant correlation between the volume indices measured by BIA and various parameter of cardiac function. The Left Ventricular Hypertrophy (LVH) group exhibited higher levels of the percentage of Extracellular Water (ECW%) and the percentage of Total Body Water (TBW%) compared to the Non-LVH group. Extracellular Water (ECW) and Third Interstitial Fluid Volume (TSFV) were identified as independent risk factors for Left Ventricular Mass (LVM), and both demonstrated a high predictive value for LVM. ECW% emerged as an independent risk factor for the Left Ventricular Mass Index (LVMI), with a high predictive value for LVMI. CONCLUSION: ECW and TSFV were found to be positively associated with cardiac function parameters in HD patients.

Identification of immune-related genes and small-molecule drugs in hypertension-induced left ventricular hypertrophy based on machine learning algorithms and molecular docking.

Background: Left ventricular hypertrophy (LVH) is a common consequence of hypertension and can lead to heart failure. The immune response plays an important role in hypertensive LVH; however, there is no comprehensive method to investigate the mechanistic relationships between immune response and hypertensive LVH or to find novel therapeutic targets. This study aimed to screen hub immune-related genes involved in hypertensive LVH as well as to explore immune target-based therapeutic drugs. Materials and methods: RNA-sequencing data from a mouse model generated by angiotensin II infusion were subjected to weighted gene co-expression network analysis (WGCNA) to identify core expression modules. Machine learning algorithms were applied to screen immune-related LVH characteristic genes. Heart structures were evaluated by echocardiography and cardiac magnetic resonance imaging (CMRI). Validation of hub genes was conducted by RT-qPCR and western blot. Using the Connectivity Map database and molecular docking, potential small-molecule drugs were explored. Results: A total of 1215 differentially expressed genes were obtained, most of which were significantly enriched in immunoregulation and collagen synthesis. WGCNA and multiple machine learning strategies uncovered six hub immune-related genes (Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3) that may accurately predict hypertensive LVH diagnosis. Immune analysis revealed that fibroblasts and macrophages were closely correlated with hypertensive LVH, and hub gene expression was significantly associated with these immune cells. A regulatory network of transcription factor-mRNA and a ceRNA network of miRNA-lncRNA was established. Notably, six hub immune-related genes were significantly increased in the hypertensive LVH model, which were positively linked to left ventricle wall thickness. Finally, 12 small-molecule compounds with the potential to reverse the high expression of hub genes were ruled out as potential therapeutic agents for hypertensive LVH. Conclusion: This study identified and validated six hub immune-related genes that may play essential roles in hypertensive LVH, providing new insights into the potential pathogenesis of cardiac remodeling and novel targets for medical interventions.

Wellens Syndrome in a patient with a history of hypertension and chronic obstructive pulmonary disease: a case report.

Wellens syndrome, an ST Elevation Myocardial Infarction (STEMI) equivalent, is also known as T-wave left anterior descending (LAD) coronary artery disease. Wellens syndrome is characterized by a unique electrocardiogram (ECG) pattern that suggests a significant stenosis in the left anterior descending coronary artery that warrants immediate intervention. Hereby, we present a case report of Wellens syndrome in a patient with a history of hypertension and chronic obstructive pulmonary disease (COPD) that may be potentially mistaken for pseudo- Wellens syndrome because the ECG pattern mimics left ventricular strain pattern (LVSP) in left ventricular hypertrophy (LVH). Thus, cautious examination of recent chest pain and ECG is important to differentiate Wellens syndrome and LVSP in patients with hypertension and COPD to perform early detection and aggressive intervention since they may help to lessen the adverse results.

Sex-related differences in hypertrophy response and cardiac expression of G protein-coupled estrogen receptor in rats with pressure overload.

There is increasing evidence that gender impacts the onset and progression of cardiovascular pathology. However, it is vastly unclear how this variable determines the ultimate outcomes, particularly in the setting of pressure overload-induced left ventricular hypertrophy (LVH). This study was carried out to fill this gap, at least in part, by assessing myocardial expression of G protein-coupled estrogen receptor (GPER) in female and male rats afflicted with LVH. Both female and male rats underwent abdominal aorta banding to induce LVH or were kept intact as control groups. At the end of the experiment, carotid artery catheterization was performed to measure systolic (SBP) and diastolic (DBP) blood pressure. Fibrosis and cardiomyocyte cross-sectional area were assessed by conventional histological analyses. Protein and mRNA expression were evaluated by Western blot/immunofluorescence staining and real-time RT-PCR technique, respectively. In LVH groups, male rats exhibited higher SBP and DBP, heart weight to body weight ratio, and fibrosis compared with female rats. However, both sexes showed a similar increase in cardiomyocyte size after LVH induction. In female, but not in male rats, LVH instigated the GPER mRNA and protein expression in the heart. These results, confirm a significant interaction between gender and myocardial remodeling in terms of GPER expression. Thus, it can be argued that sex differences in the cardiac GPER expression may be responsible for sex differences in the pressure overload-induced LVH. In other words, the female heart seems to unleash stronger protection against pressure overload than that of males in light of a higher GPER expression.

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).

The heart rate non-dipping pattern was associated with target organ damage in patients with chronic kidney disease.

PURPOSE: We performed the study to investigate the association between heart rate (HR) non-dipping pattern and target organ damage in patients with chronic kidney disease (CKD) and hypertension. METHODS: In this cross-sectional study, 447 patients with CKD and hypertension were enrolled. 24 h ambulatory blood pressure monitoring was conducted. Linear regression and logistic regression analysis were conducted to investigate the association between HR non-dipping pattern and target organ damage, including estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and left ventricular hypertrophy (LVH). RESULTS: Overall, 261 patients (58.4%) followed non-dipping patterns of HR. HR non-dipping pattern remained to be significantly associated with reduced eGFR (ß: -0.384; 95% CI: -0.719 to -0.050; p = 0.025) and the higher prevalence of CKD stages 4-5 (OR: 2.141; 95% CI: 1.153 to 3.977; p = 0.016). Meanwhile, HR non-dipping pattern was independently associated with LVMI (ß: 0.021; 95% CI: 0.000 to 0.041; p = 0.049) and LVH (OR: 1.78; 95% CI: 1.07 to 2.96; p = 0.027) after adjusting for confounding factors. CONCLUSIONS: HR non-dipping pattern was independently associated with impaired renal function and cardiac damage. Non-dipping HR deserves further attention and needs to be detected and treated during the management of CKD patients.

Transthyretin amyloid cardiomyopathy in patients with unexplained increased left ventricular wall thickness.

Amyloid cardiomyopathy (CA) was previously considered a rare disease; however, rapid advancements in imaging modalities have led to an increased frequency of its diagnosis. The aim of this prospective study was to assess the prevalence and clinical phenotype of transthyretin amyloidosis (ATTR) cardiomyopathy in patients exhibiting unexplained increased left ventricular (LV) wall thickness. From 2020 to 2022, we enrolled 100 consecutive adults with unexplained increased LV wall thickness in the study. The analysis included clinical data, electrocardiography, transthoracic echocardiography, single-photon emission computed tomography/computed tomography with 3,3-disphono-1,2-propanodicarboxylic acid, genetic testing. Overall, 18% of patients were diagnosed with CA, comprising 5% with light-chain amyloidosis, and 12% with ATTR. To evaluate associations with the ATTR diagnosis, a LOGIT model and multivariate analysis were applied. Notably, age, polyneuropathy, gastropathy, carpal tunnel syndrome, lumbar spine stenosis, low voltage, ventricular arrhythmia, LV mass, LV ejection fraction, global longitudinal strain (GLS), E/A, E/E', right ventricle (RV) thickness, right atrium area, RV VTI, TAPSE, apical sparing, ground glass appearance of myocardium, thickening of interatrial septum, thickening of valves, and the "5-5-5" sign were found to be significantly associated with ATTR (p < 0.05). The best predictive model for ATTR diagnoses exhibited an area under the curve of 0.99, including LV mass, GLS and RV thickness. This study, conducted at a cardiology referral center, revealed that a very considerable proportion of patients with unexplained increased LV wall thickness may suffer from underlying CA. Moreover, the presence of ATTR should be considered in patients with increased LV mass accompanied by reduced GLS and RV thickening.

Maternal poor glycemic control increases risk of neonatal left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important complication of infants of diabetic mothers (IDMs). However, the defined factors, such as the influence of glycemic control, insulin administration of diabetic mothers and large for gestational age (LGA) in infants, are largely unknown on the incidence of LVH. Therefore, this study aimed to evaluate the prevalence of maternal and neonatal risk factors associated with LVH in IDMs. METHODS: This prospective analytic study was conducted at tertiary care hospitals in a 1-year period. Inborn IDMs were enrolled, and ventricular hypertrophy was identified by 2D echocardiography in the first 72 hours after birth. RESULTS: A total of 160 IDMs met the inclusion criteria, 33 (20.6%) of which had LVH. The incidence of infants with LVH born to mothers with poor glycemic control (fasting blood sugar >95 mg/dL) was significantly elevated than those with good glycemic control (45.5% vs. 14.4%, P<0.001). Twelve IDMs (12/33, 36.5%) of LVH and 17 IDMs (17/127, 13.4%) of non-LVH were LGA. IDMs with LVH, compared those with non-LVH, had significantly increased left ventricular (LV) geometry; IVSd (6.5±0.8 vs. 4.0±0, 7 mm), LV IDd (16.8±3.3 mm vs. 18.4±1.1), left ventricular ejection fraction (LVEF) (68.3±8.5% vs. 62.9±17.5%), left ventricular fraction shortening (LVFS) (35.9±6.6% vs. 32.2±5.5%), LV mass (15.3±11.6 vs. 9.3±2.5 g) and LV mass index (66.2±17.5 vs. 46.6±9.7 g/m2), all with P<0.001. There was significant correlation in LV mass with infants' weight, height and body surface area (BSA) (r=0.408, 0.337 and 0.424, respectively; P<0.001). CONCLUSIONS: The prevalence of neonatal ventricular hypertrophy in IDMs was 20.6%. Maternal poor glycemic control and LGA status in IDMs were dominant risk factors of LVH.

Association between the atherogenic index of plasma and left ventricular hypertrophy in patients with obstructive sleep apnea: a retrospective cross-sectional study.

BACKGROUND: The atherogenic index of plasma (AIP) is a simple and reliable marker of insulin resistance and is closely associated with various cardiovascular diseases (CVDs). However, the relationships between AIP and left ventricular (LV) geometric indicators have not been adequately assessed. This study was carried out to investigate the association between AIP and LV geometric abnormalities in obstructive sleep apnea (OSA) patients. METHODS: This retrospective cross-sectional study included a total of 618 OSA patients (57.3 ± 12.4 years, 73.1% males, BMI 28.1 ± 4.2 kg/m2) who underwent echocardiography. Patients with OSA were diagnosed with clinical symptoms and an apnea-hypopnea index ≥ 5.0. LV hypertrophy (LVH) was defined as left ventricular mass index (LVMIh2.7) ≥ 50.0 g/m2.7 for men and 47.0 g/m2.7 for women. AIP was calculated as log10 (TG/HDL-C). RESULTS: Compared with the non-LVH group, AIP was significantly higher in the LVH group (0.19 ± 0.29 vs 0.24 ± 0.28, P = 0.024) and the concentric LVH group (0.18 ± 0.29, 0.19 ± 0.30, 0.20 ± 0.26 and 0.29 ± 0.29 in the control, concentric remodeling, eccentric hypertrophy and concentric hypertrophy groups, respectively, P = 0.021). Meanwhile, in the group of patients with the highest AIP tertile, the levels of LVMIh2.7 (42.8 ± 10.5, 43.2 ± 9.3 and 46.1 ± 12.1 in the T1, T2 and T3 groups, respectively, P = 0.003), and the prevalence of LVH (25.2%, 24.0% and 34.6% in the T1, T2 and T3 groups, respectively, P = 0.032) and concentric LVH (10.7%, 9.8% and 20.2% in the T1, T2 and T3 groups, respectively, P = 0.053) were higher compared with those in the other groups. Positive correlations between AIP and LV geometric indicators including the LVMIh2.7, LVMIBSA, LV mass (LVM), diastolic left ventricular inner diameter (LVIDd), diastolic left ventricular posterior wall thickness (PWTd) and diastolic interventricular septal thickness (IVSTd), were revealed according to correlation analysis (P < 0.05). Furthermore, AIP was independently associated with LVMIh2.7 according to multivariate linear regression model (ß = 0.125, P = 0.001). Notably, AIP remained independently associated with an elevated risk of LVH [odds ratio (OR) = 1.317 per 1 standard deviation (SD) increment, 95% confidence interval (CI): 1.058 - 1.639, P = 0.014) and concentric LVH (OR = 1.545 per 1 SD increment, 95% CI: 1.173 - 2.035, P = 0.002) after fully adjusting for all confounding risk factors by multivariate logistic regression analyses. CONCLUSIONS: AIP was independently associated with an increased risk of LVH and concentric LVH in OSA patients. Therefore, AIP, as a practical and cost-effective test, might be useful in monitoring hypertrophic remodeling of the heart and improving CVDs risk stratification in clinical management of OSA.

Ablation of Vitamin D Signaling in Cardiomyocytes Leads to Functional Impairment and Stimulation of Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in a Left Ventricular Hypertrophy Model in Mice.

The association between vitamin D deficiency and cardiovascular disease remains a controversial issue. This study aimed to further elucidate the role of vitamin D signaling in the development of left ventricular (LV) hypertrophy and dysfunction. To ablate the vitamin D receptor (VDR) specifically in cardiomyocytes, VDRfl/fl mice were crossed with Mlcv2-Cre mice. To induce LV hypertrophy experimentally by increasing cardiac afterload, transverse aortic constriction (TAC) was employed. Sham or TAC surgery was performed in 4-month-old, male, wild-type, VDRfl/fl, Mlcv2-Cre, and cardiomyocyte-specific VDR knockout (VDRCM-KO) mice. As expected, TAC induced profound LV hypertrophy and dysfunction, evidenced by echocardiography, aortic and cardiac catheterization, cardiac histology, and LV expression profiling 4 weeks post-surgery. Sham-operated mice showed no differences between genotypes. However, TAC VDRCM-KO mice, while having comparable cardiomyocyte size and LV fibrosis to TAC VDRfl/fl controls, exhibited reduced fractional shortening and ejection fraction as measured by echocardiography. Spatial transcriptomics of heart cryosections revealed more pronounced pro-inflammatory and pro-fibrotic gene regulatory networks in the stressed cardiac tissue niches of TAC VDRCM-KO compared to VDRfl/fl mice. Hence, our study supports the notion that vitamin D signaling in cardiomyocytes plays a protective role in the stressed heart.

Cumulative effect of metabolic risk factors on left ventricular geometry in those with versus without early-onset type 2 diabetes or prediabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIM: To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D). METHODS: A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes. RESULTS: One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (ß 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (ß 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (ß ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (ß ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only. CONCLUSIONS: Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.

Central Obesity is Associated with Increased Left Ventricular Maximal Wall Thickness and Intrathoracic Adipose Tissue Measured with Cardiac Magnetic Resonance.

INTRODUCTION: Central obesity (CO), characterized by an increased waist circumference increases the risk of cardiovascular disease (CVD) and morbidity, yet the underlying mechanisms are not fully understood. CO is often associated with general obesity, hypertension, and abnormal glucose tolerance, confounding the independent contribution of CO to CVD. AIM: We investigated the relationship of CO (without associated disorders) with left ventricular (LV) characteristics and intrathoracic adipose tissue (IAT) by cardiac magnetic resonance. METHODS: LV characteristics, epicardial (EAT), and mediastinal adipose tissue (MAT) were measured from 29 normoglycemic, normotensive males with CO but without general obesity (waist circumference >100 cm, body mass index (BMI) <30 kg/m2) and 18 non-obese male controls. RESULTS: LV maximal wall thickness (LVMWT) and IAT but not LV mass or volumes were increased in CO subjects compared to controls (LVMWT, 12.3±1.2 vs. 10.7±1.5 mm, p < 0.001; EAT, 5.5±3.0 vs. 2.2±2.0 cm2, p = 0.001; MAT, 31.0±12.8 vs. 15.4±10.7 cm2, p < 0.001). The LVMWT was ≥12 mm in 69% of subjects with CO and 22% of controls (p = 0.002). In CO suspects, EAT correlated inversely with LV end-diastolic volume index (r = - 0.403, p = 0.037) and LV stroke volume (SV) (r = - 0.425, p = 0.027). MAT correlated inversely with SV (r = - 0.427, p=0.026) and positively with LVMWT (r = 0.399, p = 0.035). Among CO subjects, the waist-to-hip ratio (WHR) was an independent predictor of LVMWT (B = 22.4, ß = 0.617, p < 0.001). The optimal cut-off with Youden's index for LV hypertrophy was identified at WHR 0.98 (sensitivity 85%, specificity 89%). CONCLUSIONS: CO independent of BMI is associated with LV hypertrophy and intrathoracic adipose tissue contributing to cardiovascular burden.

Treatment with Sacubitril/Valsartan Effectively Manages Hypertension and Ameliorates Left Ventricular Hypertrophy in Hemodialysis Patients.

INTRODUCTION: The aim of this study was to investigate the role of sacubitril/valsartan in managing hypertension and cardiac remodeling in patients undergoing hemodialysis. METHODS: Hemodialysis patients with stable blood pressure control were enrolled in the study. Sacubitril/valsartan was prescribed to replace previously used angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or other antihypertensive drugs. During a 6-month follow-up period, pre-dialysis blood pressure, routine biochemical markers, and N-terminal pro-brain natriuretic peptide levels were measured. Volume status was assessed using bioelectrical impedance analysis. Endothelial damage was evaluated by measuring asymmetric dimethylarginine expression, while echocardiography and life quality assessed by Short Form-12 Health Survey were conducted at baseline and after treatment. RESULTS: The median daily dose of sacubitril/valsartan in 32 participants was 200 mg, and no obvious adverse reactions were reported. The defined daily dose of other antihypertensive drugs (baseline 2.00 ± 1.18, end point 1.46 ± 1.30, t = 3.216, p = 0.003) reduced significantly. After treatment with sacubitril/valsartan, left ventricular ejection fraction significantly increased from 64.81 ± 8.16% to 67.55 ± 5.85% (t = -4.022, p ≤ 0.001) and the thickness of posterior wall of the left ventricle reduced from 1.05 ± 0.14 cm to 1.00 ± 0.11 cm (t = 2.063, p = 0.048). The interventricular septal thickness (baseline 1.08 ± 0.16 cm, endpoint 1.02 ± 0.12 cm, t = 2.260, p = 0.031) remarkably reduced by the end of follow-up. The tricuspid regurgitation pressure gradient decreased from 28.47 ± 8.26 mm Hg at baseline to 23.79 ± 6.61 mm Hg (t = 2.531, p = 0.020) after treatment. CONCLUSION: Sacubitril/valsartan effectively manages hypertension in hemodialysis patients and may also independently improve left ventricular hypertrophy and systolic function, regardless of changes in the blood pressure or the volume load.