UNASSIGNED: The diagnosis of heart failure with preserved ejection fraction (HFpEF) in the clinical setting remains challenging, especially in patients with obesity.
UNASSIGNED: This study aimed to identify novel predictors of HFpEF well suited for patients with obesity.
UNASSIGNED: We performed a retrospective analysis of a well-characterized cohort of patients with obesity with HFpEF (n = 404; mean body mass index [BMI] 36.6 kg/m2) and controls (n = 67). We used the machine learning algorithm Gradient Boosting Machine to analyze the association of various parameters with the diagnosis of HFpEF and subsequently created a multivariate logistic model for the diagnosis.
UNASSIGNED: Gradient Boosting Machine identified BMI, estimated glomerular filtration rate, left ventricular mass index, and left atrial to left ventricular volume ratio as the strongest predictors of HFpEF. These variables were used to build a model that identified HFpEF with a sensitivity of 0.83, a specificity of 0.82, and an area under the curve (AUC) of 0.88. Internal validation of the model with optimism-adjusted AUC showed an AUC of 0.87. Within the studied cohort, the novel score outperformed the H2FPEF score (AUC: 0.88 vs 0.74; P < 0.001).
UNASSIGNED: In a HFpEF cohort with obesity, BMI, estimated glomerular filtration rate, left ventricular mass index, and left atrial to left ventricular volume ratio most correlated with the identification of HFpEF, and a score based on these variables (HFpEF-JH score) outperformed the currently used H2PEF score. Further validation of this novel score is warranted, as it may facilitate improved diagnostic accuracy of HFpEF, particularly in patients with obesity.

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.

UNASSIGNED: Increased leisure-time physical activity (LTPA) is linked with decreased mortality risk, while also with increased left ventricular mass, which may induce left ventricular hypertrophy (LVH). We investigated whether LVH modifies the association between higher LTPA and lower mortality risk in population at high cardiovascular risk.
UNASSIGNED: In a prospective national cohort, we used the left ventricular mass/body surface area (LVM/BSA) method to define LVH. Baseline LTPA was self-reported and divided into: low ( < 500 metabolic equivalent of task [MET]) min/week), moderate (500-1999 MET min/week) and high ( ≥ 2000 MET-min/week). Analyses of the dose-response relationship between LTPA and left ventricular mass were performed using restricted cubic spline regression. A multivariate adjusted Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs).
UNASSIGNED: A total of 163,006 participants (55.3% females, mean [standard deviation] age, 62.4 [7.4] years) were included. During a median of 4.8 years of follow-up, 6586 (4.0%) died from all causes and 3024 (1.9%) from cardiovascular causes. Multivariate adjusted Cox proportional hazards regression analyses revealed that moderate and high LTPA were linked with less cardiovascular and all-cause mortality risk than low LTPA in the absence of LVH. In those with LVH, the association of high (0.83, 0.69-0.99) or moderate (0.72, 0.56-0.91) LTPA with cardiovascular mortality risk persisted. For all-cause mortality risk, this association was only significant in high LTPA (0.73, 0.61-0.86), while marginal in moderate LTPA (0.96, 0.84 to 1.08). Overall, the correlation patterns between LTPA and mortality risk appears distinct between those with LVH and those without LVH; the modification of LVH was not significant regarding mortality risk among the high cardiovascular risk population (all-cause: p-value for interaction = 0.074; cardiovascular cause: p-value for interaction = 0.581), except in females regarding all-cause mortality risk (p-value for interaction = 0.006).
UNASSIGNED: The association between higher LTPA and lower mortality risk was not modified by LVH in high cardiovascular risk population. However, the presence of LVH altered this association in females regarding the all-cause mortality risk.

UNASSIGNED: Carotid-femoral pulse wave velocity (cfPWV) and ejection duration (ED) have different impacts on target organ damage (TOD). The aim of this study was to determine the relationship of cfPWV and ED with TOD.
UNASSIGNED: A total of 1254 patients (64.27% males) from Ruijin Hospital were enrolled in this study from December 2018 to August 2022. Medical records, blood samples and urine samples were collected. The cfPWV was measured and ED was generated using SphygmoCor software (version 8.0, AtCor Medical, Sydney, Australia). TOD including left ventricular hypertrophy (LVH), microalbuminuria, chronic kidney disease (CKD), and abnormality of carotid intima-media thickness (CIMT) were evaluated.
UNASSIGNED: Multiple stepwise linear regression models of cfPWV and ED (individually or together) showed that cfPWV was positively correlated with left ventricular mass index (LVMI) ( β = 0.131, p = 0.002) and Log (albumin-creatinine ratio, ACR) ( β = 0.123, p = 0.004), while ED was negatively correlated with LVMI ( β = -0.244, p < 0.001) and positively correlated with the estimated glomerular filtration rate (eGFR) ( β = 0.115, p = 0.003). When cfPWV and ED were added separately or together in multiple stepwise logistic regression models, cfPWV was associated with CKD [odds ratio (OR) = 1.240, 95% confidence interval (CI) 1.055-1.458, p = 0.009], while ED was associated with LVH (OR = 0.983, 95% CI 0.975-0.992, p < 0.001). In the control group with normal cfPWV and normal ED, LVH was significantly lower in patients with high ED (OR = 0.574, 95% CI 0.374-0.882, p = 0.011), but significantly elevated in those with high cfPWV and low ED (OR = 6.799, 95% CI 1.305-35.427, p = 0.023).
UNASSIGNED: cfPWV was more strongly associated with renal damage, while ED was more strongly associated with cardiac dysfunction. cfPWV and ED affect each other, and together have an effect on LVH.

In patients with Fabry disease (FD), cardiovascular involvement is the main cause of death and reduction of quality of life. Left ventricular hypertrophy mimicking hypertrophic cardiomyopathy is the main feature of FD cardiac involvement although glycolipid storage occurs in all cardiac cellular types. Accumulation of lysosomal globotriasylceramide represents the main mechanism of cardiac damage in early stages, but secondary pathways of cellular and tissue damage, triggered by lysosomal storage, and including altered energy production, inflammation and cell death, contribute to cardiac damage and disease progression. These mechanisms appear prominent in more advanced stages, hampering and reducing the efficacy of FD-specific treatments. Therefore, additional cardiovascular therapies are important to manage cardiovascular symptoms and reduce cardiovascular events. Although new therapies targeting lysosomal storage are in development, a better definition and comprehension of the complex pathophysiology of cardiac damage in FD, may lead to identify new therapeutic targets beyond storage and new therapeutic strategies.

Fabry disease is a rare X-linked inherited lysosomal storage disorder caused by the absence or reduction of alfa-galactosidase A activity in lysosomes, resulting in accumulation of glycosphingolipids in various tissues. The main organ affected is the heart, which frequently manifests as left ventricular hypertrophy and can ultimately lead to cardiac fibrosis, heart failure, valve disease, cardiac conduction abnormalities and sudden cardiac death. Today we know that myocyte damage starts before these signs and symptoms are detectable on routine studies, during the designated pre-clinical phase of Fabry disease. The initiation of specific therapy for Fabry disease during the early stages of the disease has a great impact on the prognosis of these patients avoiding progression to irreversible fibrosis and preventing cardiovascular complications. Cardiac imaging has become an essential tool in the management of Fabry disease as it can help physicians suspect the disorder, diagnose patients in the early stages and improve outcomes. The recent development of novel imaging techniques makes necessary an update on the subject. This review discusses the role of multimodal imaging in the diagnosis, staging, patient selection for treatment and prognosis of Fabry disease and discusses recent advances in imaging techniques that provide new insights into the pathogenesis of the disorder and the possibility of novel treatment targets.

UNASSIGNED: The main objective of this study was to determine whether myocardial strain and myocardial work are altered in hypertension and whether the strain is independent of hypertension-induced left ventricular hypertrophy.
UNASSIGNED: Two systematic literature searches were conducted using Medline and EMBASE through to June 30, 2022. In the first, search terms left ventricular strain or speckle tracking AND hypertension and left ventricular hypertrophy were used in conjunction with Boolean operators to identify articles reporting left ventricular strain in patients with hypertension. In the second, the terms Global cardiac or myocardial work AND hypertension were used to identify articles. Publication bias was assessed by examination of funnel plots and calculation of the Failsafe N and Duval and Tweedie\'s Trim and fill. The results were presented as Forrest plots.
UNASSIGNED: Global longitudinal strain (GLS) was significantly lower in patients with hypertension compared to those without hypertension with a mean difference of 2.0 ± 0.1 (standard error of mean(SEM)) in the fixed effect model. Global circumferential strain (GCS) was significantly lower in hypertension. The mean difference between the hypertensive and non-hypertensive groups was 1.37 ± 0.17. Global radial strain (GRS) was significantly (p < 0.05) greater in hypertension. However, this difference was significant in only 3 and of borderline significance in 3 of 14 studies where GRS was measured. The mean difference between the hypertensive and non-hypertensive groups was 1.5 ± 0.5 using the fixed effects model. There was a significant relationship between GLS and GCS as well as between GCS and GRS but no significant relationship between GLS and GRS. There was no significant difference in left ventricular ejection fraction (LVEF) between the hypertension and no hypertension groups. There was no significant relationship between LVEF and either GLS or GCS but a significant negative correlation was found between LVEF and GRS. GLS was further reduced in persons with hypertension and left ventricular hypertrophy (LVH) compared to hypertension without LVH. In contrast, there were no or minimal differences in GCS and GRS for individuals with hypertension and LVH compared to those without LVH. Global myocardial work index (GWI) and Global constructive work (GCW) were significantly greater in patients with hypertension compared to controls. Global wasted work (GWW) indicated significantly less wasted work in controls compared to hypertension. In contrast, Global work efficiency (GWE) was significantly lower in hypertension compared to the control.
UNASSIGNED: There was a significant reduction in GLS and GCS in hypertension while GRS was increased. The reduction in GLS in hypertension was not dependent on the presence of LVH. GLS was further reduced in persons with hypertension when LVH was present. In contrast, there were no or minimal differences in GCS and GRS for individuals with LVH compared to those without LVH. GLS was independent of left ventricle (LV) ejection fraction. GWI, GCW and GWW were greater in hypertension while GWE was lower in hypertension compared to controls. These data support the contention that GLS and indices of global work are early markers of hypertensive heart disease.

Following long-term hypertension, mechanical stretching and neuroendocrine stimulation, cause multiple heterogeneous cells of the heart to interact, and result in myocardial remodeling with myocardial hypertrophy and fibrosis. The immune system, specifically macrophages, plays a vital role in this process. Macrophages are heterogeneous and plastic. Regulated by factors such as microenvironment and cytokines, polarization can be divided into two main forms: M1/M2, with different polarizations playing different roles in left ventricular structural remodeling associated with hypertension. However, descriptions of macrophage phenotypes in hypertension-induced myocardial hypertrophy models are not completely consistent. This article summarizes the phenotypes of macrophages in several models, aiming to assist researchers in studying macrophage phenotypes in hypertension-induced left ventricular structural remodeling models.

Introduction: The aim of this study was to evaluate the age at onset, clinical course, and patterns of left ventricular (LV) remodelling during follow-up in children and young patients with hypertrophic cardiomyopathy (HCM). Methods: We included consecutive patients with sarcomeric or non-syndromic HCM below 18 years old. Three pre-specified patterns of LV remodelling were assessed: maximal LV wall thickness (MLVWT) thickening; MLVWT thinning with preserved LV ejection fraction; and MLVWT thinning with progressive reduction in LV ejection fraction (hypokinetic end-stage evolution). Results: Fifty-three patients with sarcomeric/non-syndromic HCM (mean age 9.4 ± 5.5 years, 68% male) fulfilled the inclusion criteria. In total, 32 patients (60%) showed LV remodelling: 3 patients (6%) exhibited MLVWT thinning; 16 patients (30%) showed MLVWT thickening; and 13 patients (24%) progressed to hypokinetic end-stage HCM. Twenty-one patients (40%) had no LV remodelling during follow-up. In multivariate analysis, MLVWT was a predictor of the hypokinetic end-stage remodelling pattern during follow-up (OR 1.17 [95%CI 1.01-1.36] per 1 mm increase, p-value 0.043), regardless of sarcomeric variants and New York Heart Association class. Two patients with sarcomeric HCM, showing a pattern of MLVWT regression during childhood, experienced progression during adolescence. Conclusions: Different patterns of LV remodelling were observed in a cohort of children with sarcomeric/non-syndromic HCM. Interestingly, a pattern of progressive MLVWT thinning during childhood, with new progression of MLVWT during adolescence, was noted. A better understanding of the remodelling mechanisms in children with sarcomeric HCM may be relevant to defining the timing and possible efficacy of new targeted therapies in the preclinical stage of the disease.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder that commonly manifests cardiovascular complications. We aimed to assess the prevalence of FD in a Chinese population with left ventricular hypertrophy (LVH) whilst implementing a gender-specific screening approach. Methods: Patients with LVH, defined as a maximum thickness of the left ventricular septal/posterior wall ≥ 13 mm, were considered eligible. All patients with hypertrophic cardiomyopathy (HCM) were excluded. Plasma α-galactosidase (α-GLA) enzyme activity was assessed using a dried blood spot test. Males with low enzyme activity underwent genetic testing to confirm a diagnosis of FD whereas females were screened for both α-GLA and globotriaosylsphingosine concentration and underwent genetic analysis of the GLA gene only if testing positive for ≥1 parameter. Results: 426 unrelated patients (age = 64.6 ± 13.0 years; female: male = 113:313) were evaluated. FD was diagnosed in 3 unrelated patients (age = 69.0 ± 3.5 years, female: male = 1:2) and 1 related female subject (age = 43 years). Genetic analyses confirmed the late-onset cardiac variant GLA c.640-801G>A (n = 3) and the missense variant c.869T>C associated with classic FD (n = 1). Cardiac complications were the only significant findings associated with the late-onset c.640-801G>A mutation, manifesting as mild or severe concentric LVH. In contrast, the classic c.869T>C mutation FD exhibited multisystemic manifestations in addition to severe concentric LVH. Conclusions: The prevalence of FD is lower in Chinese patients with LVH when HCM is excluded. The pathological variant c.640-801G>A remains the most common cause of late-onset FD, while the detection of FD in females can be improved by utilizing a gender-specific screening method.