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Background: Evidence on the association of arterial stiffness and left ventricular (LV) concentric remodelling/LVH assessed by echocardiography, with abnormal blood pressure (BP) phenotypes, defined by office and ambulatory BP monitoring (ABPM) in the community is scanty. Thus, we investigated this issue in the participants to the Pressioni Monitorate E Loro Associazioni (PAMELA) study., Methods: The present study included 491 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, blood examinations, office, ABPM, echocardiographic and Cardio-Ankle Vascular Index (CAVI) measurements., Results: In the whole study sample (age 66+10 years, 50% males), the prevalence rates of sustained normotension (NT), white coat hypertension (WCH), masked hypertension (MH), sustained hypertension (SH) and non-dipping (ND) were 31.2, 10.0, 24.2, 34.6, and 35.8% and respectively. The likelihood of having SH, the BP phenotype carrying the greatest CV risk, was four times higher (OR= 4.31, CI:2.39-7.76, p<0.0001) in participants with increased CAVI and LV remodelling/LVH compared to their counterparts without organ damage. This association showed an incremental value in discriminating SH compared to both isolated markers of organ damage (OR=1.92,p=0.03 for increased CAVI and OR= 2.02, p=0.02 for LV remodelling/LVH). The presence of isolated but also combined organ damage was unrelated to ND., Conclusions: Our study provides new evidence of the incremental value of looking for both vascular and cardiac target organ damage to optimize the identification and clinical management of SH in the general population., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Background: Although, it is well-recognized that conventional BP alone may not be enough to determine target organ changes associated with hypertension and in cardiovascular events risk assessment, there is scarcity of data on this topic., Objectives: To determine how central BP compares with conventional BP in their association with left ventricular mass index (LVMI), among hypertensive patients., Methods: Ninety-five participants were evaluated. Conventional office BP were measured following standard procedures. And central BP was assessed using a well-validated, noninvasive pulsepen tonometric device employing generalized transfer function (GTF) interfaced with a computer. The BP parameters of both procedures were evaluated and the beta-coefficient and the corresponding coefficient of determination (R2) against the LVMI which was determined by echocardiography method and the results compared., Results: The respective β-coefficient and R2 were as follows; for the systolic BPs, central vs office BP (0.2278, .0299 vs 0.0541, .0018). Diastolic BPs, central vs office BP (0.2030, .0651 vs 0.2050, .0075). For pulse pressure (PP), central vs office PP (0.2673,.0133 vs 0.182, .0100). For Mean arterial pressure (MAP) central vs office BPs (0.2253, .0161 vs 0.2048, .0107). Also evaluated were the central forward pressure (Pf) (β-coefficient =0.2073, and R2 = .0086), backward/reflected pressure wave (Pb) (β-coefficient =0.7034, and R2 = .0133,), the reflection magnitude (RM =Pb/Pf) (β-coefficient =0.8073, and R2 = .0986) and the pulse wave velocity (PWV) (β-coefficient =0.7408, and R2 = .0047)., Conclusions: Central BP indices may have association with LVM-indexed to the height2.7, beyond that shown by conventional BP parameters taken at the arm., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Background: Hypertrophic cardiomyopathy is an autosomal dominant cardiac disease. The mechanisms that determine its variable expressivity are poorly understood. Epigenetics could play a crucial role in bridging the gap between genotype and phenotype by orchestrating the interplay between the environment and the genome regulation. In this study we aimed to establish a possible correlation between the peripheral blood DNA methylation patterns and left ventricular hypertrophy severity in patients with hypertrophic cardiomyopathy, evaluating the potential impact of lifestyle variables and providing a biological context to the observed changes., Methods and Results: Methylation data were obtained from peripheral blood samples (Infinium MethylationEPIC BeadChip arrays). We employed multiple pair-matched models to extract genomic positions whose methylation correlates with the degree of left ventricular hypertrophy in 3 monozygotic twin pairs carrying the same founder pathogenic variant ( MYBPC3 p.Gly263Ter). This model enables the isolation of the environmental influence, beyond age, on DNA methylation changes by removing the genetic background. Our results revealed a more anxious personality among more severely affected individuals. We identified 56 differentially methylated positions that exhibited moderate, proportional changes in methylation associated with left ventricular hypertrophy. These differentially methylated positions were enriched in regions regulated by repressor histone marks and tended to cluster at genes involved in left ventricular hypertrophy development, such as HOXA5 , TRPC3 , UCN3 , or PLSCR2 , suggesting that changes in peripheral blood may reflect myocardial alterations., Conclusions: We present a unique pair-matched model, based on 3 monozygotic twin pairs carrying the same founder pathogenic variant and different phenotypes. This study provides further evidence of the pivotal role of epigenetics in hypertrophic cardiomyopathy variable expressivity.

Left ventricular hypertrophy (LVH) caused by chronic pressure overload with subsequent pathological remodeling is a major cardiovascular risk factor for heart failure and mortality. The role of deubiquitinases in LVH has not been well characterized. To define whether the deubiquitinase ubiquitin-specific peptidase 20 (USP20) regulates LVH, we subjected USP20 knockout (KO) and cognate wild-type (WT) mice to chronic pressure overload by transverse aortic constriction (TAC) and measured changes in cardiac function by serial echocardiography followed by histological and biochemical evaluations. USP20-KO mice showed severe deterioration of systolic function within 4 wk of TAC compared with WT cohorts. Both USP20-KO TAC and WT-TAC cohorts presented cardiac hypertrophy following pressure overload. However, USP20-KO-TAC mice showed an increase in cardiomyocyte length and developed maladaptive eccentric hypertrophy, a phenotype generally observed with volume overload states and decompensated heart failure. In contrast, WT-TAC mice displayed an increase in cardiomyocyte width, producing concentric remodeling that is characteristic of pressure overload. In addition, cardiomyocyte apoptosis, interstitial fibrosis, and mouse mortality were augmented in USP20-KO-TAC compared with WT-TAC mice. Quantitative mass spectrometry of LV tissue revealed that the expression of sarcomeric myosin heavy chain 7 (MYH7), a fetal gene normally upregulated during cardiac remodeling, was significantly reduced in USP20-KO after TAC. Mechanistically, we identified increased degradative lysine-48 polyubiquitination of MYH7 in USP20-KO hearts, indicating that USP20-mediated deubiquitination likely prevents protein degradation of MYH7 during pressure overload. Our findings suggest that USP20-dependent signaling pathways regulate the layering pattern of sarcomeres to suppress maladaptive remodeling during chronic pressure overload and prevent cardiac failure. NEW & NOTEWORTHY We identify ubiquitin-specific peptidase 20 (USP20) as an important enzyme that is required for cardiac homeostasis and function, particularly during myocardial pressure overload. USP20 regulates protein stability of cardiac MYH7, an essential molecular motor protein expressed in sarcomeres; loss-of-function mutations of MYH7 are associated with human hypertrophic cardiomyopathy, cardiac failure, and sudden death. Enhancing USP20 activity could be a potential therapeutic approach to prevent the development of maladaptive state of eccentric hypertrophy and heart failure.

Background: Myocardial injury is common in end-stage renal disease (ESRD) patients, but the presence and severity of myocardial injury in different left ventricular (LV) phenotypes were still not fully explored., Purpose: To evaluate myocardial tissue characteristics and deformation in ESRD patients on peritoneal dialysis separated into normal geometry, concentric remodeling, concentric left ventricular hypertrophy (LVH) and eccentric LVH patterns by multiparametric cardiac MRI., Study Type: Prospective., Population: A total of 142 subjects, including 102 on peritoneal dialysis (69 males) and 40 healthy controls (27 males)., Field Strength/sequence: At 3.0 T, cine sequence, T1 mapping and T2 mapping., Assessment: LV mass index and LV remodeling index were used to create four subgroups with normal geometry, concentric remodeling, concentric LVH, and eccentric LVH. LV function, strain and strain rate, myocardial native T1 and T2 were measured., Statistical Tests: Descriptive statistics, analysis of variance and analysis of covariance, Pearson/Spearman correlation, stepwise regression, and intraclass correlation coefficient. P-value <0.05 was considered statistically significant., Results: Even in normal geometry, LV strain parameters still diminished compared with the controls (global radial strain: 30.5 ± 7.7% vs. 37.1 ± 7.9%; global circumferential strain: -18.2 ± 2.6% vs. -20.6 ± 2.2%; global longitudinal strain: -13.3 ± 2.5% vs. -16.0 ± 2.8%). Eccentric LVH had significantly lower global circumferential systolic strain rate than concentric LVH (-0.82 ± 0.21%/ - second vs. -0.96 ± 0.20%/ - second). Compared with the controls, the four subgroups all revealed elevated native T1 and T2, especially in eccentric LVH, while concentric remodeling had the least changes including native T1, T2, and LV ejection fraction. After adjusting for covariates, there was no statistically significant difference in T2 between the four subgroups (P = 0.359)., Data Conclusions: Eccentric LVH is associated with the most pronounced evidence of myocardial tissue characteristics and function impairment, while as a benign remodeling, the concentric remodeling subgroup had the least increase in native T1. This study further confirms that native T1 and strain indicators can reflect the severity of myocardial injury in ESRD, providing better histological and functional basis for future grouping treatments., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 3., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Myocardial work is a novel echocardiographic measure that offers detailed insights into cardiac mechanics. We sought to characterize cardiac function by myocardial work in patients with chronic kidney disease (CKD)., Methods: We prospectively enrolled 757 patients with non-dialysis-dependent CKD and 174 age- and sex-matched controls. Echocardiographic pressure-strain loop analysis was performed to acquire the global work index (GWI). Linear regressions were performed to investigate the association between estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) to GWI., Results: Patients with CKD had a mean age of 57 years, 61% were men, and median eGFR was 42 mL/min/1.73 m 2 . Overall, no difference in GWI was observed between patients and controls (1879 vs. 1943 mmHg%, p = 0.06). However, a stepwise decline in GWI was observed for controls vs. patients with CKD without left ventricular hypertrophy vs. patients with CKD and left ventricular hypertrophy (GWI, 1943 vs. 1887 vs. 1789 mmHg%; p for trend = 0.030). In patients with CKD, eGFR was not associated with GWI by linear regression. However, diabetes modified this association (p for interaction = 0.007), such that per 10 mL/min/1.73 m 2 decrease in eGFR, GWI decreased by 22 (9-35) mmHg% (p = 0.001) after multivariable adjustments in patients without diabetes, but with no association between eGFR and GWI in patients with diabetes. No association was observed between UACR and GWI., Conclusion: Patients with CKD and left ventricular hypertrophy exhibited lower myocardial work compared to matched controls. Furthermore, decreasing eGFR was associated with decreasing myocardial work only in patients without diabetes. No association to UACR was observed., (© 2024. The Author(s).)

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are now recommended for patients with heart failure, but the mechanisms that underlie the protective role of SGLT2i in cardiac remodeling remain unclear. Aldehyde dehydrogenase 2 (ALDH2) effectively prevents cardiac remodeling. Here, the key role of ALDH2 in the efficacy of SGLT2i on cardiac remodeling was studied., Methods: Analysis of multiple transcriptomic datasets and two-sample Mendelian randomization were performed to find out the differentially expressed genes between pathological cardiac hypertrophy models (patients) and controls. A pathological cardiac hypertrophy mouse model was established via transverse aortic constriction (TAC) or isoproterenol (ISO). Cardiomyocyte-specific ALDH2 knockout mice (ALDH2 CMKO ) and littermate control mice (ALDH2 flox/flox ) were generated to determine the critical role of ALDH2 in the preventive effects of dapagliflozin (DAPA) on cardiac remodeling. RNA sequencing, gene knockdown or overexpression, bisulfite sequencing PCR, and luciferase reporter assays were performed to explore the underlying molecular mechanisms involved., Results: Only ALDH2 was differentially expressed when the differentially expressed genes obtained via Mendelian analysis and the differentially expressed genes obtained from the multiple transcriptome datasets were combined. Mendelian analysis revealed that ALDH2 was negatively related to the severity of myocardial hypertrophy in patients. DAPA alleviated cardiac remodeling in mouse hearts subjected to TAC or ISO. ALDH2 expression was reduced, whereas ALDH2 expression was restored by DAPA in hypertrophic hearts. Cardiomyocyte specific ALDH2 knockout abolished the protective role of DAPA in preventing cardiac remodeling. ALDH2 expression and activity were increased in DAPA-treated neonatal rat primary cardiomyocytes (NRCMs), H9C2 cells and AC16 cells. Moreover, DAPA upregulated ALDH2 in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes. Sodium/proton exchanger 1 (NHE1) inhibition contributed to the regulation of ALDH2 by DAPA. DAPA suppressed the production of reactive oxygen species (ROS), downregulated DNA methyltransferase 1 (DNMT1) and subsequently reduced the ALDH2 promoter methylation level. Further studies revealed that DAPA enhanced the binding of nuclear transcription factor Y, subunit A (NFYA) to the promoter region of ALDH2, which was due to the decreased promoter methylation level of ALDH2., Conclusions: The upregulation of ALDH2 plays a critical role in the protection of DAPA against cardiac remodeling. DAPA enhances the binding of NFYA to the ALDH2 promoter by reducing the ALDH2 promoter methylation level through NHE1/ROS/DNMT1 pathway., (© 2024. The Author(s).)

Background: The therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure., Methods: We conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e' >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) levels, were also assessed., Results: A total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (- 15.5 ± 3.1% to - 16.6 ± 2.8%, P = 0.004) compared to the placebo group (- 16.7 ± 2.7% to - 16.4 ± 2.6%, P = 0.509), with a significant between-group difference (P = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA 1c , systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro-B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1-7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [r = 0.456, P < 0.001 for ACE2; r = 0.541, P < 0.001 for angiotensin (1-7)]. Adverse events were similar between the two groups., Conclusions: This study demonstrated that ertugliflozin has beneficial effects on left ventricular function in individuals with type 2 diabetes and pre-heart failure, and it provided insights into potential underlying mechanisms., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT03717194., (© 2024. The Author(s).)

Background: This study aimed to quantitatively evaluate the left ventricular global and regional myocardial work of patients in Fabry disease (FD) by echocardiographic pressure-strain loop (PSL) analysis., Results: The study included 48 patients with FD and 48 healthy controls matched for age and sex. According to the presence/absence of left ventricular hypertrophy (LVH), the patients with FD were divided into an LVH + group and an LVH- group. Left ventricular blood pressure was estimated noninvasively according to echocardiographic valvular events and systolic pressure in the brachial artery. Left ventricular myocardial work parameters were acquired by echocardiographic pressure-strain loop analysis. The FD groups had a significantly lower global longitudinal strain (GLS), global work index, global work efficiency (GWE), global constructive work and higher global waste work than the control group (P < .05). Regional analysis showed that all segmental myocardial waste work increased and myocardial work efficiency decreased in the LVH + group than in the LVH- group (P < .05). Segmental longitudinal strain, myocardial work index, and myocardial constructive work were markedly lower in the basal and middle segments (P < .05) and preserved in the apical segments. Multivariate analysis revealed that GWE and GLS were significant related to LVH., Conclusions: Myocardial work analysis can be used to assess global and regional myocardial work in patients with FD. In this study, GLS and GWE were reduced in patients with FD and associated with the presence of LVH. Basal and middle myocardial work decreased in relation to the LVH, while apical myocardial work remained, which added value to explore the distribution of myocardial impairment., (© 2024. The Author(s).)

Exposure to winter cold causes an increase in energy demands to meet the challenge of thermoregulation. In small rodents, this increase in cardiac output leads to a profound cardiac hypertrophy, 2-3 times that typically seen with exercise training. The nature of this hypertrophy and its relevance to winter mortality remains unclear. Our goal was to characterize cold-induced cardiac hypertrophy and to assess its similarity to either exercise-induced (physiological) hypertrophy or the pathological hypertrophy of hypertension. We hypothesized that cold-induced hypertrophy will most closely resemble exercise-induced hypertrophy, but be another unique pathway for physiological cardiac growth. We found that cold-induced hypertrophy was largely reversed after a return to warm temperatures. Further, metabolic rates were elevated while gene expression and mitochondrial enzyme activities indicative of pathology were absent. A gene expression panel comparing hearts of exercised and cold-exposed mice further suggests that these activities are similar, although not identical. In conclusion, we found that chronic cold led to a phenotype that most closely resembled physiological hypertrophy, with enhanced metabolic rate, without induction of fetal genes, but with decreased expression of genes associated with fatty acid oxidation, suggesting that heart failure is not a cause of winter mortality in small rodents and identifying a novel approach for the study of cardiac growth., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Aim: To (1) compare QT dispersion (QTd) and echocardiographic features between athletes with concentric left ventricular (LV) hypertrophy, athletes with eccentric LV hypertrophy, and sedentary controls with a normal LV geometric pattern and (2) quantify associations between QTd and echocardiographic features within these groups., Methods: Male athletes competing in different sports and sedentary men were stratified into groups according to their LV geometric pattern. These groups included eccentric LV hypertrophy (LV index > 115 g/m 2 , relative wall thickness [RWT] < 0.42) consisting of 38 athletes, concentric LV hypertrophy (LV index > 115 g/m 2 , RWT > 0.42) consisting of 40 athletes, and normal LV geometric pattern (LV index < 115 g/m 2 , RWT < 0.42) consisting of 40 sedentary controls. Following a cross-sectional design, participants underwent electrocardiographic (ECG) and echocardiographic screening. Data were compared between groups using one-way analyses of variance with Bonferroni post hoc tests. Associations between corrected QTd and echocardiographic variables were quantified using Pearson correlations., Results: Alongside structural disparities between groups, corrected QTd was significantly (p < 0.001) lower in athletes with eccentric LV hypertrophy compared to athletes with concentric LV hypertrophy and sedentary controls. Significant, moderate-to-very-large correlations were found between corrected QTd and interventricular septal wall thickness in athletes with concentric (r = 0.416, p = 0.008) or eccentric LV hypertrophy (r = 0.734, p < 0.001), and sedentary controls (r = 0.464, p = 0.003)., Conclusion: The provided comparative and relationship data may inform the development of more precise approaches for ECG and echocardiographic screening in athletes, particularly in those with concentric LV hypertrophy who may be at greater risk for developing prolonged QTd., (© 2024 Wiley Periodicals LLC.)

Background: Left ventricular hypertrophy (LVH) is most common when driven by hypertension, and it is a strong independent risk factor for adverse cardiovascular events and death. Some animal models support a role for gut microbiota and metabolites in the development of LVH, but cohort studies confirming these findings in populations are lacking., Methods and Results: We investigated the alterations of gut microbiota and metabolites in 30 patients with hypertension, 30 patients with hypertensive LVH, and 30 matched controls on the basis of 16S rDNA and metabolomic analyses. Thirty stool and 90 serum samples were collected in fasting conditions. ANOVA/Kruskal-Wallis/Pearson's χ 2 /Fisher's exact test and Bonferroni's correction were used ( P <0.0167) for comparison among the 3 groups. A regression analysis and subgroup analysis were performed between gut microbiota and left ventricular mass index (LVMI) and metabolites and LVMI, respectively. Spearman correlation analysis was performed between metabolites and flora and metabolites and LVMI. We observed LVH-enriched Faecalitalea (β=6758.55 [95% CI, 2080.92-11436.18]; P =0.009), Turicibacter (β=8424.76 [95% CI, 2494.05-14355.47]; P =0.01), Ruminococcus torques group (β=840.88 [95% CI, 223.1-1458.67]; P =0.013), and Erysipelotrichaceae UCG-003 (β=856.37 [95% CI, 182.76-1529.98]; P =0.019) were positively correlated with LVMI. A total of 1141 (in sera) and 2657 (in feces) metabolites were identified. There was a sex-specific association between metabolites and LVMI. Significant changes in metabolic pathways in LVH were also observed, especially bile acid and lipid metabolism pathways., Conclusions: Our study demonstrated the disordered gut microbiota and microbial metabolite profiles in LVH. This highlights the roles of gut bacteria and metabolite in this disease and could lead to new intervention, diagnostic, or management paradigms for LVH., Registration: URL: https://www.chictr.org.cn; Unique Identifier: ChiCTR2200055603.

Background: The association between aortic valve stenosis (AVS) and myocardial perfusion abnormalities has been incompletely characterized. We sought to assess the predictors of myocardial ischemia in patients with mild-to-moderate AVS, and its relationship with long-term prognosis., Methods: Eighty-nine patients with mild-to-moderate AVS (peak velocity between 2.6 and 4.0 m/second and aortic valve area > .6 cm 2 /m 2 ), preserved left ventricular (LV) function, and either normal coronary arteries (28 patients) or non-obstructive coronary artery disease (<50% stenosis; 61 patients) were individuated. Myocardial perfusion imaging was performed using a cadmium-zinc-telluride camera, and the summed difference score (SDS) was computed. The presence of either LV hypertrophy (LVH) (LV mass index [LVMI] > 115 g/m 2 [males] or 95 g/m 2 [females]) or concentric LV remodeling (relative wall thickness: >.42) was determined at two-dimensional echocardiography., Results: Forty (45%) and 49 (55%) patients had mild and moderate AVS, respectively. Fifty (56%), 17 (19%), and 22 (25%) patients had normal LV geometry, concentric LV remodeling, and LVH, respectively. An interaction between LV remodeling and inducible ischemia was revealed with progressively higher values of SDS in patients with normal LV geometry (3 ± 3), concentric remodeling (4 ± 2), and LVH (7 ± 2) (P < .001). Accordingly, a moderate correlation existed between LVMI and SDS values (R: .67; P < .001). After a median follow-up of 84 ± 47 months, 27 adverse events were recorded, including 19 AV replacements and 8 deaths. On multivariable analysis, the presence of LVH (hazard ratio [HR]: 6.46; 95% confidence interval [CI]: 2.09-20.00; P = .001) and a higher SDS (HR: 1.41; 95% CI: 1.15-1.75; P = .001) were the two independent predictors of AE., Conclusions: In patients with mild-to-moderate AVS, myocardial ischemia correlates with the severity of adverse LV remodeling. Patients with LVH and ischemia are at increased risk of AE., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the association between metabolically healthy obesity (MHO) and left ventricular geometric remodelling in Chinese children., Materials and Methods: This cross-sectional study used data from two population-based samples in China, including 2871 children aged 6-11 years. Weight status was defined based on body mass index according to the World Health Organization growth chart. Metabolic status was defined based on the 2018 consensus-based criteria proposed by Damanhoury et al. Obes Rev 2018;19:1476-1491 (blood pressure, lipids and glucose). Left ventricular geometric remodelling was determined as concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. Multinomial logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for the association between categories of weight and metabolic status and left ventricular geometric remodelling., Results: Compared with children with metabolically healthy normal weight, those with MHO had higher odds of left ventricular geometric remodelling, with adjusted ORs (95% CIs) of 2.01 (1.23-3.28) for concentric remodelling, 6.36 (4.03-10.04) for eccentric hypertrophy, and 17.07 (7.97-36.58) for concentric hypertrophy. Corresponding ORs (95% CIs) were 2.35 (1.47-3.75), 10.85 (7.11-16.55), and 18.56 (8.63-39.94), respectively, for children with metabolically unhealthy obesity. In contrast, metabolically unhealthy normal weight was not associated with higher odds of left ventricular geometric remodelling. Findings were consistent in sensitivity analyses that used different definitions of weight and metabolic status and left ventricular geometric remodelling., Conclusions: Children with MHO had higher odds of left ventricular geometric remodelling than their metabolically healthy normal weight counterparts. Our findings suggest MHO may not be a benign condition for cardiac health in children., (© 2024 John Wiley & Sons Ltd.)

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 (β: -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 (β: 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., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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 (β = 0.342; P = 0.001). Maximal intima-media thickness was significantly associated with older age (β = 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., Competing Interests: Conflicts of interest The authors declare they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Left ventricular global longitudinal strain (LV GLS) on echocardiography is a sensitive yet clinically significant marker of myocardial dysfunction. Reduced LV GLS is prevalent in adults with chronic kidney disease and hypertension and is associated with adverse cardiovascular outcomes. It may be a biomarker of chronic kidney disease-associated myocardial dysfunction in children, but data are limited. Our objective was to describe LV GLS in the CKiD study (Chronic Kidney Disease in Children) and to examine the association between blood pressure (BP) and reduced LV GLS., Methods: A single apical 4-chamber view was used to estimate LV GLS. Our main analyses examined the association of clinic BP with the absolute value of LV GLS and LV GLS dichotomized at 16. Sensitivity analyses using 24-hour ambulatory BP monitoring data were also performed. Generalized estimating equations were used to account for within-person correlation and to estimate robust SEs for 95% CIs. Covariates in adjusted models included: age, sex, race, estimated glomerular filtration rate, urine protein, hemoglobin, left ventricular hypertrophy, and the use of renin-angiotensin system inhibitors., Results: LV GLS was measured in 962 person-visits. A total of 77 assessments had an LV GLS <16. In adjusted models, both clinic systolic BP (odds ratio, 1.02 [95% CI, 1.01-1.03]) and diastolic BP (odds ratio, 1.02 [95% CI, 1.00-1.03]) percentiles were associated with LV GLS <16. Having awake or nighttime diastolic BP hypertension on ambulatory BP monitoring was significantly associated with a lower absolute value of LV GLS., Conclusions: Office systolic and diastolic hypertension was associated with diminished LV GLS. Only diastolic hypertension detected on ambulatory BP monitoring was associated with lower LV GLS., Competing Interests: None.

Background and Aims: The Chinese visceral adipose index (CVAI) is more significantly associated with cardiometabolic risk factors than other obesity indices. This study investigated the relationship between CVAI and left ventricular (LV) remodeling., Methods and Results: This study included 75,132 Koreans who underwent echocardiography during a health checkup. They were grouped according to quartile levels of the CVAI, body mass index (BMI), waist circumference (WC), and visceral adiposity index (VAI). LV remodeling was defined as the presence of abnormal relative wall thickness (ARWT) and left ventricular hypertrophy (LVH). Multivariate adjusted logistic regression analysis (adjusted OR [95% confidence interval]) was used to analyze the association between ARWT and LVH according to the quartile levels of each index. Receiver operating characteristic (ROC) graphs and areas under the curve (AUC) were calculated to identify the predictive ability of the indices for ARWT and LVH. ARWT was associated proportionally with CVAI quartiles in both men (second quartile: 1.42 [1.29-1.56], third quartile: 1.61 [1.46-1.77], fourth quartile: 2.01 [1.84-2.21]), and women (second quartile: 1.06 [0.78-1.45], third quartile: 1.15 [0.86-1.55], and fourth quartile: 2.09 [1.56-2.80]). LVH was significantly associated with third (1.74 [1.07-2.83]) and fourth quartile (1.94 [1.18-3.20]) groups of CVAI in women. ROC and AUC analyses indicated that CVAI was superior to other indices in predicting ARWT in men and LVH and ARWT in women., Conclusion: The CVAI is an effective surrogate marker of LV remodeling, particularly in women., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Accumulating evidence supports the efficacy of renal denervation (RDN) as an antihypertensive treatment. Additionally, several RDN clinical studies, including meta-analyses, have suggested that RDN may potentially have beneficial effects on left ventricular hypertrophy, diastolic function, and new-onset/recurrence of atrial fibrillation (AF), although most studies were not randomized sham-controlled. In particular, the effects of RDN on left ventricular hypertrophy and AF recurrence appear to be relatively evident. Sympathetic activation plays a critical role in the development of hypertension, hypertensive heart disease, and AF. Notably, several studies suggest the cardioprotective effects of RDN even in the absence of significant blood pressure reduction, probably due to its sympathoinhibitory effects. It is imperative to establish the efficacy of RDN in patients with hypertensive heart disease and/or AF, focusing on parameters of sympathetic activity in the clinical setting, including randomized sham-controlled trials. Moreover, further basic research is essential to elucidate the therapeutic mechanisms of RDN beyond blood pressure lowering and the renal nerves-linked pathophysiologies of hypertensive heart disease and AF. This review outlines the effects of renal denervation on hypertensive heart disease, particularly on left ventricular hypertrophy and diastolic function, and on atrial fibrillation. The sympathoinhibitory effect of renal denervation, an important potential mechanism of its beneficial effects on heart disease, is also discussed., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Aims: Cardiac amyloidosis is a diffuse disease affecting all cardiac chambers. The value of right ventricular free-wall strain is uncertain as an echocardiographic red flag. We hypothesized that right ventricular free-wall strain is of added value for diagnostic and prognostic purposes in patients with transthyretin cardiac amyloidosis (ATTR-CA)., Method: A diagnosis of ATTR-CA required positive Tc-99m pyrophosphate scintigraphy and negative serum clonal dyscrasia. Patients with left ventricular (LV) hypertrophy (LVH; interventricular septal thickness ≥1.2 cm) by echocardiography and negative pyrophosphate scintigraphy served as controls after exclusion of amyloid light-chain cardiac amyloidosis. Longitudinal strain was computed with speckle-tracking echocardiography., Results: We studied 108 subjects with ATTR-CA and 106 controls with LVH, retrospectively. Right ventricular free-wall strain was independently associated with the diagnosis of ATTR-CA after adjusting for classical echocardiographic parameters, namely, relative apical sparing (RAS), e', and E/e'. Right ventricular free-wall strain ≥ -16% was incremental to LV RAS in the overall group and in the subgroup without extreme wall thickness (≤1.4 cm; Harrell's C, net reclassification improvement = 0.213, P < .001; and net reclassification improvement = 0.463, P = .015, respectively). Major adverse cardiovascular and cerebrovascular events (heart failure hospitalization, stroke, death) occurred in 47 ATTR-CA patients, during follow-up (median, 38; range, 6-60 months). Right ventricular free-wall strain ≥-16% was associated with 3-fold increased risk of MACCE in ATTR-CA patients independently of age, comorbidities, B-type natriuretic peptide, and tafamidis treatment. Right ventricular free-wall strain was additive to LV ejection fraction for risk stratification (chi square = 10.2; P = .017)., Conclusions: Right ventricular free-wall strain >-16% has incremental value to LV RAS for the differential diagnosis of ATTR-CA among LVH phenotypes and is associated with poor prognosis., Competing Interests: Conflicts of Interest None., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the association between the extent of nocturnal systolic blood pressure decline and left ventricular hypertrophy in patients with primary hypertension who were receiving antihypertensive drug therapy., Design: This was a cross-sectional hospital-based study from November 2020 to March 2021., Setting: The study was conducted at the Polyclinic of Korle Bu Teaching Hospital, Ghana., Participants: Outpatients ≥18 years old with primary hypertension who were receiving antihypertensive drug therapy., Interventions: Each participant underwent a 24-hour ambulatory blood pressure monitoring and a transthoracic echocardiogram., Main Outcome Measures: Left ventricular hypertrophy and the extent of mean systolic blood pressure decline during sleep., Results: 180 participants were recruited, comprising 110 (61.1%) females. The participants' mean (±SD) age was 57.6 ± 11.0 years. 80% had a non-dipping blood pressure pattern, and 43.9% had left ventricular hypertrophy. Uncontrolled office blood pressure was an independent predictor of left ventricular hypertrophy in these patients (AOR 2.010, 95% CI 1.048-3.855, p=0.036); however, a non-dipping nocturnal systolic blood pressure status was not (AOR 1.849, 95% CI 0.850-4.022, p=0.121). 61.1% had abnormal left ventricular geometry, with concentric hypertrophy being the predominant geometric pattern., Conclusion: Left ventricular hypertrophy and non-dipping nocturnal blood pressure were common in these hypertensive Ghanaian patients on antihypertensive therapy. Left ventricular hypertrophy was associated with uncontrolled office blood pressure but not the extent of nocturnal systolic blood pressure declines during a single 24-hour ambulatory blood pressure recording., Funding: None declared., Competing Interests: Conflict of interest: None declared, (Copyright © The Author(s).)

Non-infarctional Q-waves in general are often recorded in the ECG, and are attributed to anatomical and electrical ECG axis shifts, presence of accessory pathways, pregnancy, HCM, and other HCM-like segmental LV myocardial hypertrophic states, that are currently not fully characterized, as to their nosological nature. The present focused review concerns in particular inferior Q-waves and their association with segmental basal anterior and/or septal LV hypertophies due to HCM, and other not yet fully characterized basal segmental LV hypertophies. Insights from the currently available literature on the topic are reviewed, and varying opinions about the nature of such hypertophic states are discussed, with some suggestions, for what is needed to be done, for their further pathlogenetic characterization., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Left ventricular (LV) hypertrophy (LVH) is frequently observed in patients with hypertension (HTN). LV myocardial work (MW) has recently emerged as a non-invasive method to assess systolic myocardial deformation relative to afterload conditions. The authors investigated the characteristics of myocardial work with different degrees of LVH in HTN patients. From December 2020 to February 2024, 255 HTN patients and 26 healthy controls undergoing transthoracic echocardiography were included in the current study. Hypertension patients were divided into quintile groups based on left ventricular mass index (LVMI), for the first to fourth LVMI quantiles, global work index (GWI) and global constructive work (GCW) were higher compared to the control group, but the difference was not statistically significant. In the sixth LVMI quantile, GWI and GCW showed a significant decrease. The restricted cubic splines showed that both GWI and GCW exhibited an inverted U-shaped relationship with LVMI. A LVMI of >151.39 g/m 2 could accurately predict reduction both in GWI and GCW (Sensitivity: 0.78, Specificity: 0.89, AUC: 0.90, P < .001; Sensitivity: 0.81, Specificity: 0.92, AUC: 0.92, P < .001, respectively). As LVH progressed in HTN patients, both GWI and GCW initially demonstrated an increase, followed by a subsequent decrease. Myocardial work provides additional insights into assessment of cardiac function in HTN patients., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Rotational mechanics is a fundamental determinant of left ventricular ejection fraction (LVEF). The coding system currently employed in clinical practice does not distinguish between rotational patterns. We propose an alternative coding system that makes possible to identify the rotational pattern of the LV and relate it to myocardial function. Echocardiographic images were used to generate speckle tracking-derived transmural global longitudinal strain (tGLS) and rotational parameters. The existence of twist (basal and apical rotations in opposite directions) is expressed as a rotational gradient with a positive value that is the sum of the basal and apical rotation angles. Conversely, when there is rigid rotation (basal and apical rotations in the same direction) the resulting gradient is assigned a negative value that is the subtraction between the two rotation angles. The rotational patterns were evaluated in 87 healthy subjects and 248 patients with LV hypertrophy (LVH) and contrasted with their myocardial function. Our approach allowed us to distinguish between the different rotational patterns. Twist pattern was present in healthy controls and 104 patients with LVH and normal myocardial function (tGLS ≥ 17%, both). Among 144 patients with LVH and myocardial dysfunction (tGLS < 17%), twist was detected in 83.3% and rigid rotation in 16.7%. LVEF was < 50% in 34.7%, and all patients with rigid rotation had a LVEF < 50%. The gradient rotational values showed a close relationship with LVEF (r = 0.73; p < 0.001). The proposed coding system allows us to identify the rotational patterns of the LV and to relate their values with LVEF., (© 2024. The Author(s).)

In the initial stage, left ventricular hypertrophy (LVH) is adaptive, but in time, it transforms to maladaptive LVH which is specific for the development of various phenotypes that cause heart failure, initially with preserved, but later with reduced left ventricular ejection fraction. Pathophysiological mechanisms, which are characteristic for remodeling procedure, are numerous and extremely complex, and should be subjected to further research with the aim of making a comprehensive overview of hypertensive heart disease (HHD) and discovering new options for preventing and treating HHD. The contemporary methods, such as cardiac magnetic resonance (CMR) and computed tomography (CT) provide very accurate morphological and functional information on HHD. The objective of this review article is to summarize the available scientific information in terms of prevalence, pathophysiology, diagnostics, prevention, contemporary therapeutic options, as well as to present potential therapeutic solutions based on the research of pathological mechanisms which are at the core of HHD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Patients with aortic dissection have a high prevalence of left ventricular structural alterations, including left ventricular hypertrophy (LVH), but little is known about the impact of sex on this regard. This study compared clinical, cardiac, and prognostic characteristics between men and women with aortic dissection., Methods: We retrospectively assessed clinical and echocardiographic characteristics, and 1-year mortality in 367 aortic dissection patients (30% women; 66% with Stanford-A) who underwent echocardiography 60 days before or after the diagnosis of aortic dissection from three Brazilian centers., Results: Men and women had similar clinical characteristics, except for higher age (59.4 ± 13.4 vs. 55.9 ± 11.6 years; P  = 0.013) and use of antihypertensive classes (1.4 ± 1.3 vs. 1.1 ± 1.2; P  = 0.024) and diuretics (32 vs. 19%; P  = 0.004) in women compared with men. Women had a higher prevalence of LVH (78 vs. 65%; P  = 0.010) and lower prevalence of normal left ventricular geometry (20 vs. 10%; P  = 0.015) than men. Logistic regression analysis adjusted for confounding factors showed that women were less likely to have normal left ventricular geometry (odds ratio, 95% confidence interval = 0.42, 0.20-0.87; P  = 0.019) and were more likely to have LVH (odds ratio, 95% confidence interval = 1.91, 1.11-3.27; P  = 0.019). Conversely, multivariable Cox-regression analysis showed that women had a similar risk of death compared to men 1 year after aortic dissection diagnosis (hazard ratio, 95% confidence interval = 1.16, 0.77-1.75; P  = 0.49)., Conclusion: In aortic dissection patients, women were typically older, had higher use of antihypertensive medications, and exhibited a greater prevalence of LVH compared with men. However, 1-year mortality after aortic dissection diagnosis did not differ between men and women., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: To evaluate the consistency between fractal dimensions (FD) derived from cardiac computed tomography (CT-FD) and cardiac magnetic resonance (MR-FD) in assessing left ventricular trabecular complexity., Methods: This retrospective study included 170 patients who underwent CCT and CMR scans within two weeks. Five short-axis cine images were selected at end-diastole: one basal, three mid, and one apical slice. Short-axis CCT views were reconstructed and aligned with the cine images. CT-FD and MR-FD values were calculated for each slice, with mean values determined for each patient. Severe left ventricular hypertrophy (LVH) was defined as a maximum wall thickness > 15 mm in end-diastolic cine images., Results: The diastolic CT-FD and MR-FD values exhibited high consistency, with values of 1.253 ± 0.091 and 1.250 ± 0.102, respectively (n = 535, ICC = 0.882, 95 % CI: 0.861-0.899, P < 0.001). Similarly, the systolic CT-FD and MR-FD values demonstrated good consistency, with values of 1.268 ± 0.072 and 1.286 ± 0.093, respectively (n = 390, ICC = 0.720, 95 % CI: 0.669-0.765, P < 0.001). For subgroups of systolic NLVH and LVH, the ICCs were 0.773 (n = 305, CI: 0.723-0.814, P < 0.001) and 0.565 (n = 85, 95 % CI: 0.402-0.694, P < 0.001), respectively. The diagnostic efficacy of mean CT-FD aligned with that of mean MR-FD in distinguishing abnormal cardiac conditions from the CMR-negative group., Conclusions: CCT is a feasible method for assessing left ventricular trabecular complexity, with good agreement with CMR, except in cases of severe left ventricular hypertrophy during systole., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Current guidelines recommend suspecting transthyretin amyloid cardiomyopathy (ATTR-CM) in patients over 65 years of age with unexplained left ventricular (LV) hypertrophy in a non-dilated LV, heart failure (HF) and preserved ejection fraction (HFpEF), hypertrophic cardiomyopathy or severe aortic stenosis. However, there is evidence indicating a high prevalence of ATTR-CM in other HF phenotypes. As such, this study aimed to characterize the diversity of HF phenotypes of ATTR-CM by examining the LV ejection fraction and LV dilatation using echocardiography., Methods: This multicentre, retrospective observational study included patients diagnosed with ATTR-CM between 2015-2023. The diagnosis was based on a positive cardiac biopsy or positive bone scintigraphy without monoclonal gammopathy. Echocardiographic measurements were categorized according to LV ejection fraction (LVEF) into HFpEF (LVEF ≥50%), HF with mildly reduced EF (HFmrEF, LVEF 40-49%), and HF with reduced EF (HFrEF, LVEF <40%). LV cavity size was categorized by LV end-diastolic diameter (LVEDD) and volume index (LVEDVi) as normal, moderately increased and severe dilatation., Results: The study included 135 patients with ATTR-CM (mean age, 78 years; 89% male; 89% wild-type ATTR-CM). Most patients were screened for ATTR-CM because of unexplained HF and increased LV wall thickness (57%). Echocardiography showed LVEF <50% in 60% of the patients, with a significant portion presenting with HFrEF. Patients with LVEF <50% had higher NYHA class and elevated N-terminal pro-B-type natriuretic peptide levels than HFpEF patients. LV dilatation was observed in 43% of the patients, with 10% presenting with both LVEF <50% and severe LV dilatation., Conclusion: This study revealed significant variability in HF phenotypes among patients with ATTR-CM, from HFpEF without LV dilatation to HFrEF with severe LV dilatation. Relying solely on HFpEF for screening may lead to under-diagnosis. These findings suggest the need for more comprehensive diagnostic criteria beyond echocardiographic measures to improve ATTR-CM detection and management.

(-)-Epicatechin (EPI) is beneficial for cardiovascular health. Trimethylamine N-oxide (TMAO), a gut microbe-derived food metabolite, is strongly associated with the risk of cardiovascular diseases. However, the effects and underlying mechanisms of EPI on TMAO-induced cardiac hypertrophy remain unclear. This study aimed to determine whether EPI inhibits TMAO-induced cardiac hypertrophy. Plasma levels of TMAO in control participants and patients with cardiac hypertrophy were measured and analyzed. Male C57BL/6 mice were randomly divided into control group, TMAO group, EPI group and TMAO + EPI group. According to the groups assignments, mice received intraperitoneal (i.p.) injection of normal saline or i.p. injection of TMAO (150 mg/kg/day) for 14 days. The EPI group was given intragastric (i.g.) administration of EPI alone (1 mg/kg/day) for 21 days, and TMAO + EPI group received i.g. administration of EPI for 7 days before starting i.p. injection of TMAO, continuing until the end of the TMAO treatment. Histological analyses of the mice's hearts was accessed by H&E and Masson staining. In vitro, H9c2 cells were induced to hypertrophy by TMAO (10 µM) for 24 h and were pre-treated with or without EPI (10 µM) for 1 h. Protein level of cardiac hypertrophy markers and Sp1/SIRT1/SUMO1 pathway were determined by western blot. The plasma level of TMAO was 2.66 ± 1.59 μmol/L in patients with cardiac hypertrophy and 0.62 ± 0.30 μmol/L in control participants. EPI attenuated TMAO-induced hypertrophy in H9c2 cells. In vivo, TMAO induced cardiac hypertrophy and impaired the cardiac function of mice. Pathological staining showed that TMAO induced cardiac hypertrophy and collagen deposition in mice. EPI treatment improved the cardiac function, inhibited the myocardial hypertrophy induced by TMAO. EPI significantly attenuated the TMAO-induced upregulation of ANP and BNP and the downregulation of SP1, SIRT1 and SUMO1 in vivo and in vitro. EPI may suppress TMAO-induced cardiac hypertrophy by activating the Sp1/SIRT1/SUMO1 signaling pathway., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical Approval The study was approved by the Institutional Ethics Committees of the First Affiliated Hospital of Harbin Medical University (No. IRB-AF/SC-08/05.0). The present study was conducted according to the “Guide for the Care and Use of Laboratory Animals” (NIH Publication No.85-23, revised in 1996). The animal experiments were approved by the Institutional Animal Care and Use Committee of First Affiliated Hospital, Harbin Medical University. Consent to Participate The study protocols and the procedures for handling human samples were approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University (Harbin, China). All patients provided informed consent, and all the methods were carried out in accordance with the approved guidelines. Consent for Publication Not applicable., (© 2024. The Author(s).)

Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Background: Multiple target-organ damages (TODs) in the same patient are common and further increase the risk of cardiovascular disease. However, the relationship between ambulatory central systolic blood pressure (SBP) and multiple TODs has yet to be explored., Methods and Results: MobilO-Graph PWA was used to monitor the participants' ambulatory blood pressure, and the presence of left ventricular hypertrophy, carotid hypertrophy, and kidney injury were used to define TOD. Logistic regression analyses and receiver operating characteristic analyses were used to explore the correlation between SBP and TOD. Overall, 2018 nondialysis patients with chronic kidney disease were included and 580 (28.74%) had multiple TODs. Twenty-four-hour central SBP with c2 calibration exhibited a stronger correlation with the increasing number of TOD compared with 24-hour brachial SBP in ordinal logistic regression analyses. In the multivariable analyses with the presence of multiple TODs, the odds ratios were 1.786 (95% CI, 1.474-2.165; P <0.001) for 24-hour brachial SBP and 1.949 (95% CI, 1.605-2.366; P <0.001) for 24-hour central SBP with c2 calibration. The receiver operating characteristic analyses also showed that 24-hour central SBP with c2 calibration had higher discrimination than 24-hour brachial SBP regarding multiple TODs ( P <0.001). In addition, using 130/135 mm Hg as the threshold for 24-hour brachial SBP/central SBP with c2 calibration to cross-classify, the prevalence of multiple TODs was greater in cases of concordant hypertension compared with cases of isolated brachial hypertension and concordant normotension, with no difference between the latter 2 conditions., Conclusions: Twenty-four-hour central SBP with c2 calibration was more associated with the presence of multiple TODs compared with 24-hour brachial SBP and was helpful in risk classification of multiple TODs among nondialysis patients with chronic kidney disease.

Competing Interests: Competing interests: None declared.

Background: This study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR)., Methods: Six-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal-Wallis and Dunn., Results: Echocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p < 0.05 vs T and SNAC) and diastolic posterior wall thickness (S 1.50 ± 0.12; T 1.52 ± 0.10; SNAC 1.56 ± 0.12; TNAC 1.62 ± 0.14 * mm; * p < 0.05 vs T), with improved contractile function (posterior wall shortening velocity: S 39.4 ± 5.01; T 36.4 ± 2.96; SNAC 39.7 ± 3.44; TNAC 41.6 ± 3.57 * mm/s; * p < 0.05 vs T). Myocardial lipid hydroperoxide concentration was lower in NAC treated groups (S 210 ± 48; T 182 ± 43; SNAC 159 ± 33 *; TNAC 110 ± 23 * # nmol/g tissue; * p < 0.05 vs S, # p < 0.05 vs T and SNAC). Nox 2 and p22 phox expression was higher and p47 phox lower in T than S [S 1.37 (0.66-1.66); T 0.78 (0.61-1.04) *; SNAC 1.07 (1.01-1.38); TNAC 1.06 (1.01-1.15) arbitrary units; * p < 0.05 vs S]. NADPH oxidase subunits did not differ between TNAC, SNAC, and S groups., Conclusion: N-acetylcysteine supplementation alone reduces oxidative stress in untreated spontaneously hypertensive rats. The combination of N-acetylcysteine and concurrent exercise further decreases oxidative stress. However, the lower oxidative stress does not translate into improved cardiac remodeling and function in untreated spontaneously hypertensive rats., (© 2024. The Author(s).)

Noonan Syndrome with Multiple Lentigines (NSML-formerly known as LEOPARD syndrome) is a rare autosomal dominant condition that usually exhibits cardiac involvement with hypertrophic cardiomyopathy (HCM). Here we present a case of a NSML patient with an unusual and patchy cardiac hypertrophy distribution., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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 (β 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (β 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 (β 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 (β 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., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

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., (© 2024. The Author(s).)

Left ventricular hypertrophy (LVH) is often used as an indicator to assess hypertension-mediated organ damage (HMOD), alongside hypertensive retinopathy (HR) and nephropathy. Assessment of HMOD is crucial when making decisions about treatment optimization. Despite longstanding debate over its reliability to detect LVH, it is common practice to perform an electrocardiogram (ECG) instead of directly assessing left ventricular mass with echocardiography. In this study, the presence of LVH was evaluated using both ECG and echocardiography among consecutive patients suspected of therapy-resistant hypertension or secondary hypertension in the outpatient clinic of the Department of Internal Medicine at the Diakonessen Hospital, Utrecht, the Netherlands, between July 15, 2017, and July 31, 2020. The primary endpoints were the specificity and sensitivity of ECG as a diagnostic tool for LVH, with echocardiography serving as the reference method. Among the 329 participants, we identified 70 individuals (21.3%) with true LVH based on echocardiography. The ECG displayed a sensitivity of 47.9% and a specificity of 75.3%. Moreover, the area under the receiver operating characteristics curve was 0.604. In conclusion, ECG demonstrates limited value in identifying LVH. Considering the importance of accurately assessing HMOD for treatment optimization of hypertension, the role of ECG as a diagnostic tool for LVH is, therefore, questionable. Instead, we recommend employing standard echocardiography as a more reliable diagnostic., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: The prognostic value of different grades of left ventricular hypertrophy (LVH) and left ventricular (LV) mechanical function in Fabry disease is unclear. We aimed to evaluate the association between the severity of LVH, LV mechanical function, and clinical outcomes in Fabry disease., Methods: We conducted a retrospective cohort study from a single-center registry of adult patients with Fabry disease. Left ventricular mass index (LVMI) was measured by echocardiography. The severity of LVH was categorized by LVMI using the sex-specific cutoff values. Left ventricular mechanical function was measured as LV global longitudinal strain (GLS) by speckle-tracking analysis. The primary outcome was a composite of major adverse cardiovascular events (MACE) at 5 years, including heart failure hospitalization, sustained ventricular tachycardia, acute ischemic stroke, and all-cause mortality., Results: The study included 268 patients (age 50.4 ± 15.4 years, men 46.6%) with Fabry disease (83.2% IVS4+919G > A mutation), and 106 patients (39.6%) had LVH. Patients with mild, moderate, or severe LVH had 5-year MACE rates of 7.4%, 10%, and 30.5%, respectively (P < .001). Moreover, patients with impaired LV GLS (<14.1%) had a higher 5-year MACE rate than those with preserved LV GLS (32.1% vs 2.4%, P < .001). Severe LVH was an independent predictor of MACE compared with absence of LVH (adjusted hazard ratio, 12.73; 95% CI, 1.3-124.71; P = .03), after adjusting for age, sex, hypertension, hyperlipidemia, atrial fibrillation, renal function, average E/e', enzyme replacement therapy, and LV GLS. Patients with severe LVH and impaired LV GLS had the highest incidence for MACE (log-rank P < .05), irrespective of sex, genotypes, and whether receiving enzyme replacement therapy or not., Conclusions: Sex-specific grading of LVH by LVMI is practical for risk stratification in patients with Fabry disease, and impaired LV GLS further refines the prognostication., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) hypertrophy is a common clinical finding. Differential diagnosis includes Fabry disease, a rare and progressive, but treatable storage disease caused by deficiency of α-galactosidase A. However, diagnosis of Fabry is often hampered by its clinical heterogeneity, LV hypertrophy phenocopies and unawareness of the clinician., Methods: This review summarises clinical data, family history, electrocardiogram (ECG) and imaging (echocardiogram and cardiovascular magnetic resonance (CMR)) characteristics to differentiate aetiologies of LV hypertrophy including clues for the diagnosis of Fabry., Results: LV hypertrophy is a consequence of pressure overload mostly, but differential diagnosis includes hypertrophic cardiomyopathy and infiltrative diseases. Clinical data, ECG, type and degree of LV hypertrophy, functional and tissue characteristics differ among aetiologies. LV hypertrophy in Fabry is progressive and mostly concentric but may copy any hypertrophic cardiomyopathy. Dependent on residual alfa-galactosidase A enzyme activity, degree of LV hypertrophy in Fabry may vary. Initially, low myocardial CMR T1-map values are calculated. At a later stage, midwall late gadolinium enhancement of the inferolateral LV wall may occur. Global longitudinal strain may be depressed in the inferolateral wall. Voltage criteria for LV hypertrophy and short PQ interval are common. Right ventricular (RV) hypertrophy is frequent. In addition, multisystemic symptoms including neuropathic pain, hypohidrosis, proteinuria, renal insufficiency and familial young stroke are pointing to Fabry., Conclusions: LV hypertrophy should raise suspicion of Fabry disease, especially if LV hypertrophy is unexplained and/or associated with RV hypertrophy. In Fabry, LV hypertrophy may be heterogeneous and mimic any hypertrophic cardiomyopathy. ECG, multisystemic symptoms and imaging may provide clues for Fabry.

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 (R 2 =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., Competing Interests: None.

Salt-sensitive hypertension is common among individuals with essential hypertension, and the prevalence of left ventricular hypertrophy (LVH) has increased. However, data from early identification of the risk of developing LVH in young adults with salt-sensitive hypertension are lacking. Thus, the present study aimed to design a nomogram for predicting the risk of developing LVH in young adults with salt-sensitive hypertension. A retrospective analysis of 580 patients with salt-sensitive hypertension was conducted. The training set consisted of 70% (n = 406) of the patients, while the validation set consisted of the remaining 30% (n = 174). Based on multivariate analysis of the training set, predictors for LVH were extracted to develop a nomogram. Discrimination curves, calibration curves, and clinical utility were employed to assess the predictive performance of the nomogram. The final simplified nomogram model included age, sex, office systolic blood pressure, duration of hypertension, abdominal obesity, triglyceride-glucose index, and estimated glomerular filtration rate (eGFR). In the training set, the model demonstrated moderate discrimination, as indicated by an area under the receiver operating characteristic (ROC) curve of 0.863 (95% confidence interval: 0.831-0.894). The calibration curve exhibited good agreement between the predicted and actual probabilities of LVH in the training set. Additionally, the validation set further confirmed the reliability of the prediction nomogram. In conclusions, the simplified nomogram, which consists of seven routine clinical variables, has shown good performance and clinical utility in identifying young adults with salt-sensitive hypertension who are at high risk of LVH at an early stage., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Cardiac hypertrophy is a common feature in several cardiomyopathies. We previously reported that loss of ADAM15 (disintegrin and metalloproteinase 15) worsened cardiac hypertrophy and dilated cardiomyopathy following cardiac pressure overload. Here, we investigated the impact of ADAM15 loss in female mice following cardiac pressure overload induced by transverse aortic constriction (TAC). Female Adam15 -/- mice developed the same degree of cardiac hypertrophy, dilation, and dysfunction as the parallel female wild-type (WT) mice at 6 wk post-TAC. To determine if this is due to the protective effects of estrogen, which could mask the negative impact of Adam15 loss, WT and Adam15 - / - mice underwent ovariectomy (OVx) 2 wk before TAC. Cardiac structure and function analyses were performed at 6 wk post-TAC. OVx similarly impacted females of both genotypes post-TAC. Calcineurin (Cn) activity was increased post-OVx-TAC, and more in Adam15 - / - mice; however, this increase was not reflected in the total-to-phospho-NFAT levels. Integrin-α 7 expression, which was upstream of Cn activation in male Adam15 - / - -TAC mice, remained unchanged in female mice. However, activation of the mitogen-activated protein kinases (ERK, JNK, P38) was greater in Adam15 - / - -OVx-TAC than in WT-OVx-TAC mice. In addition, ADAM15 protein levels were significantly increased post-TAC in male but not in female WT mice. Myocardial fibrosis was comparable in non-OVx WT-TAC and Adam15 - / - -TAC mice. OVx increased the perivascular fibrosis more in Adam15 - / - compared with WT mice post-TAC. Our data demonstrate that loss of ovarian hormones did not fully replicate the male phenotype in the female Adam15 - / - mice post-TAC. As ADAM15 levels were increased in males but not in females post-TAC, it is plausible that ADAM15 does not play a prominent role in post-TAC events in female mice. Our findings highlight the significance of factors other than sex hormones in mediating cardiomyopathies in females, which require a more thorough understanding. NEW & NOTEWORTHY Loss of ADAM15 in female mice, unlike the male mice, does not worsen the cardiomyopathy following cardiac pressure overload. Ovariectomy does not worsen the post-TAC cardiomyopathy in female Adam15 - / - mice compared with female WT mice. Lack of deleterious impact of Adam15 deficiency in female mice is not because of the protective effects of ovarian hormones but could be due to a less prominent role of ADAM15 in cardiac response to post-TAC remodeling in female mice.

Background: In this study, we examine the association between the hyperuricemia(HU) and hypertension(HTN) in Chinese young adults. Besides, the correlation between the occurrence of thickened left ventricular wall and HU was identified in patients with HTN., Methods: In all, 360 patients with HTN and 1991 young adults with normal blood pressure(NBP) were enrolled in the study. Participant characteristics were collected. Univariable and multivariable logistic regression tests were utilized to identify the correlation between the presence of HU and HTN, and the correlation between the occurrence of thickened ventricular septum and HU in patients with HTN., Results: The prevalence of HU in Chinese young adults with HTN was significantly higher than young adults with NBP(36.39% vs. 16.93%). Univariable analyses revealed that 8 factors were related with the presence of HTN with p value < 0.001, including HU, male, body mass index(BMI) ≥ 24 kg/m 2 , total cholesterol(TC) > 5.17mmol/L, triglyceride(TG) > 1.70mmol/L, high density lipoprotein cholesterol(HDL-C) < 1.0mmol/L, fasting blood glucose(FBG) > 6.10mmol/L and fatty liver. After adjusting these covariates, multivariable analysis revealed that HU[odds ratio(OR):1.47, 95% confidence interval(CI): 1.10-1.95, p = 0.008] remained independent association with HTN in young adults. Additionally, univariable and multivariable logistic analyses revealed that HU kept the independent effect on the presence of thickened interventricular septum(adjusted OR = 1.81, 95% CI: 1.05-3.11, P = 0.03) and thickened left ventricular posterior wall(adjusted OR = 2.28, 95% CI: 1.28-4.08, P = 0.005) in young adults with HTN., Conclusion: HU was independently associated with HTN in young adults. HU was independently correlated with thickened left ventricular wall, including interventricular septum and left ventricular posterior wall, in young adults with HTN., (© 2024. The Author(s).)

Background and Objectives : Left ventricular hypertrophy (LVH) represents a significant cardiovascular risk in patients undergoing chronic hemodialysis (CHD). A large inferior vena cava diameter (IVCD), potentially indicative of fluid overload and a contributing factor to elevated cardiovascular risk, has not been sufficiently explored. Therefore, our study aims to gain further insights into this aspect. Materials and Methods : A retrospective cohort study enrolled patients receiving CHD in a single medical center with available echocardiography from October to December 2018. They were categorized into four groups based on LVH geometry and IVCD. Cox proportional hazard models assessed the risk of major adverse cardiovascular effects (MACEs) and cardiovascular and overall mortality after multivariate adjustments. Kaplan-Meier analysis depicted MACE-free events and survival during the follow-up time. Results : Of the 175 CHD patients, 38, 42, 45, and 50 exhibited small IVCD with eccentric and concentric LVH and large IVCD with eccentric and concentric LVH, respectively. Compared to small IVCD and eccentric LVH, large IVCD and eccentric LVH had the highest risk of MACEs, followed by large IVCD and concentric LVH (aHR: 4.40, 3.60; 95% CI: 1.58-12.23, 1.28-10.12, respectively). As for cardiovascular mortality, large IVCD and concentric LVH had the highest risk, followed by large IVCD and eccentric LVH, and small IVCD and concentric LVH. (aHR: 14.34, 10.23, 8.87; 95% CI: 1.99-103.35, 1.41-74.33; 1.01-77.87). The trend in overall mortality risk among the groups was similar to that of cardiovascular mortality. Conclusions : LVH geometry and IVCD co-modify the risk of MACEs and cardiovascular and overall mortality in CHD patients. The highest risk of MACEs is associated with large IVCD and eccentric LVH, while the highest risk of cardiovascular and overall mortality is linked with large IVCD and concentric LVH.

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-1β (IL-1β), 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-1β (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-1β 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)., (© 2024. The Author(s).)

Background: Enzyme replacement therapy (ERT) may halt or attenuate disease progression in patients with Anderson-Fabry disease (AFD). However, whether left ventricular hypertrophy (LVH) can be prevented by early therapy or may still progress despite ERT over a long-term follow-up is still unclear., Methods: Consecutive patients with AFD from the Independent Swiss-Fabry Cohort receiving ERT who were at least followed up for 5 years were included. Cardiac progression was defined as an increase of >10 g/m 2 in left ventricular mass index (LVMI) between the first and the last available follow-up transthoracic echocardiography., Results: 60 patients (35 (23-48) years, 39 (65%) men) were followed up for 10.5 (7.2-12.2) years. 22 had LVH at ERT start (LVMI of 150±38 g/m 2 ). During follow-up, 22 (36%, 34±15 years) had LVMI progression of 12.1 (7-17.6) g/m 2 per 100 patient-years, of these 7 (11%, 29±13 years) with no LVH at baseline. Three of them progressed to LVH. LVMI progression occurred mostly in men (17 of 39 (43%) vs 5 of 21 (24%), p<0.01) and after the age of 30 years (17 of 22 (77%)). LVH at ERT start was associated with LVMI progression (OR 1.3, 95% CI 1.1 to 2.6; p=0.02). A total of 19 (31%) patients experienced a major AFD-related event. They were predominantly men (17 of 19, 89%), older (45±11 vs 32±9 years) with baseline LVH (12 of 19, 63%), and 10 of 19 (52%) presented with LVMI progression., Conclusions: Over a median follow-up of >10 years under ERT, 36% of the patients still had LVMI cardiac progression, and 32%, predominantly older men, experienced major AFD-related events. LVH at treatment initiation was a strong predictor of LVMI progression and adverse events on ERT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)