Left Ventricular Global Strain Research Articles

The impact of type 2 diabetes on left ventricular function in hypertensive patients: a three-dimensional speckle-tracking imaging study

ObjectivesThe study aimed to evaluate the impact of the co-occurrence of hypertension and type 2 diabetes mellitus (T2DM) on the deterioration of left ventricular (LV) structure and function using three-dimensional speckle-tracking imaging (3D-STI), compared to patients with only hypertension.MethodsData from 272 hypertensive patients, including 85 with T2DM and 187 without, along with 45 normal controls, were analyzed. Participant characteristics were assessed before and after propensity score matching (PSM). 3D-STI-derived parameters, including LV function and global strain parameters, were compared among controls and different patient groups. Multivariable linear regression analyses were conducted to determine the impacts of T2DM on LV function and global strain. Additionally, linear mixed-effects regression models were used to evaluate the associations between 3D-STI-derived parameters and T2DM over time in hypertensive patients.ResultsSignificant increases in the E/e' ratio and declines in the LV global radial strain (GRS) were observed across the control group, HTN (T2DM-) group, and HTN (T2DM+) group. After adjusting for various factors using PSM analysis, LV global circumferential strain (GCS) and global area strain (GAS) were also found to be significantly decreased in the HTN (T2DM+) group compared to the HTN (T2DM-) group. Multivariable regression analyses, accounting for various covariates, indicated that T2DM was independently linked to LV strains (LV GAS: β = 0.95, 95% CI: 0.90–1.00, p = 0.029; LV GRS: β = 1.03, 95% CI: 1.01–1.06, p = 0.014) in hypertensive patients. Furthermore, linear mixed-model analysis revealed that LV GCS (β = 1.20, 95% CI: 0.38–2.01, p = 0.004) and GRS (β = −2.82, 95% CI: −4.97–0.68, p = 0.010) deteriorated over the 12-month period.ConclusionsT2DM exacerbates the decline in LV global and regional strains in patients with hypertension, and 3D-STI may be a valuable tool for detecting these asymptomatic preclinical abnormalities.

The additional impact of metabolic syndrome on left ventricular deformation and myocardial energetic efficiency impairment in ischemia with nonobstructive coronary arteries patients

BackgroundIschemia with nonobstructive coronary arteries (INOCA) has high morbidity, mortality, and poor quality of life. Metabolic syndrome (MetS) is a complex of multiple cardiac metabolic risk factors, significantly increasing the risk of major adverse cardiovascular events in INOCA patients. The study aimed to investigate the aggravating effect of MetS on left ventricular (LV) deformation and function impairment in INOCA patients.Materials and methods This study collected 104 INOCA patients (INOCA [MetS−]: n = 56; INOCA [MetS+]: n = 48) and 41 sex- and age-matched controls. LV function, indexed myocardial energetic efficiency (MEEI), and LV global peak strains (including radial, circumferential, and longitudinal directions) were measured among the three groups. The independent factors of reduced MEEI and impaired LV function and strain parameters for all INOCA patients were assessed using multivariable linear regression analyses.ResultsIn contrast to the INOCA (MetS-) group, the indexed LV stroke volume (LVSVI) (49.57 ± 11.58 mL/m2 vs. 42.58 ± 12.23 mL/m2, p = 0.007), MEEI [0.85(0.70–1.03) ml/s/g vs. 0.75(0.54–0.91) ml/s/g, p = 0.045] and LV global longitudinal peak strain (GLPS) (− 13.26 ± 2.86% vs. -10.95 ± 3.93%, p = 0.001) reduced in the INOCA (MetS+) group. Compared with the controls, LV GLPS decreased in the INOCA (MetS-) group (− 15.14 ± 2.83% vs. −13.26 ± 2.86%, p = 0.017). MetS was negatively associated with LVSVI, MEEI, and LV GLPS (all p < 0.05). After multivariable adjustment, MetS was found to be an independent factor of decreased LVSVI (β = −0.231, p = 0.012), MEEI (β = −0.262, p = 0.009), and LV GLPS (β = −0.266, p = 0.002) in INOCA patients. Using calcium channel blockers medication (β = 0.320, p = 0.001) and hypertension (β = −0.298, p = 0.002) were also independently associated with impaired MEEI.ConclusionsMetS aggravated LV deformation and function impairment in patients with INOCA. MetS was found to be an independent factor of impaired MEEI and LV GLPS, the further decrease of MEEI and LV GLPS in INOCA patients caused by MetS might involve the synergistic injury mechanism. Early diagnosis and treatment of MetS in patients with INOCA are important.

High altitudes, deeper insights: multicenter cardiovascular magnetic resonance study on hypertrophic cardiomyopathy.

Altitude is a known factor in cardiovascular disease, but its impact on hypertrophic cardiomyopathy (HCM) patients remains unclear. This study aimed to determine whether living at high altitudes affects the extent of late gadolinium enhancement (LGE) and left ventricular (LV) strain in HCM patients. This retrospective cross-sectional study was conducted across four hospitals located at different altitudes in China. A total of 256 HCM patients who underwent cardiac magnetic resonance (CMR) imaging between May 2019 and November 2021 were included. Patients were categorized into two groups: the high-altitude group (median interquartile range [IQR]: 1520.00 [1520.00, 1917.00] meters, n = 132) and the low-altitude group (86.45 [43.50, 150.75] meters, n = 124). The extent of LGE and global LV strain were assessed and compared between these groups. The median age of the study population was 55 years (IQR: 46-63), with 59% of participants being male. The high-altitude group exhibited a significantly greater extent of LGE compared to the low-altitude group (median [IQR]: 8.10 [4.78, 19.98]% vs. 6.20 [1.89, 13.81]%; p = 0.008). Multivariable analysis identified altitude as an independent predictor of increased LGE extent (β = 4.41; 95% CI: 2.04 to 6.78; p < 0.001). Additionally, altitude was positively associated with LV strain in the longitudinal, circumferential, and radial directions (all p < 0.050). HCM patients living at higher altitudes exhibit a significant increase in LGE extent and more favorable LV strain parameters. Question Does altitude affect the extent of late gadolinium enhancement (LGE) and left ventricular strain in patients with hypertrophic cardiomyopathy (HCM)? Findings High altitude is associated with a significantly greater extent of LGE and less impairment in global longitudinal strain in HCM patients. Clinical relevance HCM patients living at higher altitudes exhibit a significant increase in LGE extent and the mismatch of left ventricular strains. Doctors should consider these findings to tailor treatment and follow-up plans for HCM patients living in high altitudes.

Adaptation of Left Ventricular Function and Myocardial Microstructure in Fetuses With Right Ventricular Hypoplasia.

In this study we evaluated changes in left ventricular (LV) function and myocardial microstructure in fetuses with right ventricular hypoplasia (RVH) using 2-dimensional speckle tracking echocardiography, diffusion tensor cardiovascular magnetic resonance imaging, and proteomics analysis. Fifty-one singleton fetuses diagnosed with RVH and 51 normal fetuses were retrospectively included. LV global longitudinal strain and global circumferential strain were acquired using 2-dimensional speckle tracking echocardiography. Fraction anisotropy, mean diffusivity, and helix angle were measured using diffusion tensor cardiovascular magnetic resonance imaging in 4 fetal specimens with RVH and 3 normal fetal specimens. Bioinformatics analysis was performed for differentially expressed proteins between RVH and normal specimens. In RVH fetuses, LV global longitudinal strain and regional longitudinal strain were significantly lower than in controls (P < 0.001), whereas LV sphericity index and LV global circumferential strain were increased. In RVH fetuses, fraction anisotropy was higher in middle and apical segments than in normal fetuses (P < 0.001). LV mean diffusivity was reduced in all of the segments (P < 0.001). Circumferentially oriented myocytes and left-sided oriented myocytes were increased, but right-sided oriented myocytes were decreased (P < 0.001). Using proteomics, 95 myocardial proteins differed with upregulation of 66 and downregulation in RVH hearts including myocardial contractile fibrillar proteins and cell membrane protein complexes. In fetal RVH, the left ventricle demonstrates altered function with reduced longitudinal but augmented circumferential strain, which might support its need to augment its preload and consequent cardiac output. Decreased right-sided and increased circumferentially oriented myocytes might contribute to this adaptation. The left ventricle in fetal RVH also demonstrates a differential expression of various myocardial proteins.

Association Between Sleep Quality and Cirrhotic Cardiomyopathy: A Prospective Case-Control Study.

The main purpose of this study is to evaluate the changes in sleep quality among patients with cirrhotic cardiomyopathy (CCM). The study included liver cirrhosis patients aged 18-75 from Northern Jiangsu People's Hospital Affiliated to Yangzhou University and collected their clinical examination results to assess the clinical characteristics and related risk factors of patients with CCM. The study found that the onset of CCM was not related to the etiology of inducing cirrhosis. Pittsburgh Sleep Quality Index (PSQI) score (odds ratio (OR) = 13.476, 95% confidence interval (CI) = 1.514-119.923, P = 0.020), absolute GLS (OR = 0.328, 95% CI = 0.210-0.510, P < 0.001), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR = 1.050, 95% CI = 1.025-1.076, P < 0.001) were identified as independent risk factors for inducing CCM. In patients with CCM, a decrease in sleep quality often occurs. When cirrhotic patients also have poor sleep quality, along with a decrease in absolute Global Left Ventricular Strain (GLS) levels and an increase in NT-proBNP levels, these factors may pose a higher risk for CCM development. However, further validation of these research findings is required in larger sample sizes.

Assessing coronary artery stenosis exacerbated impact on left ventricular function and deformation in metabolic syndrome patients by 3.0 T cardiac magnetic resonance imaging

BackgroundMetabolic syndrome (MetS) and coronary artery stenosis (CAS) independently increase the risk of cardiovascular events, while the impact of CAS on left ventricular (LV) function and deformation in MetS patients remains unclear. This study investigates how varying degrees of CAS exacerbate LV function and myocardial deformation in MetS patients.MethodsOne hundred thirty-one MetS patients who underwent CMR examinations were divided into two groups: the MetS(CAS−) group (n = 47) and the MetS(CAS+) group (n = 84). The MetS(CAS+) group was divided into MetS with non-obstructive CAS(NOCAS+) (n = 30) and MetS with obstructive CAS(OCAS+) group (n = 54). Additionally, 48 age- and sex-matched subjects were included as a control group. LV functional and deformation parameters were measured and compared among subgroups. The determinants of decreased LV global peak strains in all MetS patients were identified using linear regression. The receiver operating characteristic (ROC) curve and logistic regression model (LRM) evaluated the diagnostic accuracy of the degree of CAS for identifying impaired LV strain.ResultsCompared to MetS(CAS−), MetS(NOCAS+) showed a significantly increased LV mass index (p < 0.05). Global longitudinal peak strain was decreased gradually from MetS(CAS−) through MetS(NOCAS+) to MetS(OCAS+) (− 13.02 ± 2.32% vs. − 10.34 ± 4.05% vs. − 7.55 ± 4.48%, p < 0.05). MetS(OCAS+) groups showed significantly decreased LV global peak strain (GPS), PSSR and PDSR in radial and circumferential directions compared with MetS(NOCAS+) (all p < 0.05). The degree of CAS was independently associated with impaired global radial peak strain (GRPS) (β = − 0.289, p < 0.001) and global longitudinal peak strain (GLPS) (β = 0.254, p = 0.004) in MetS patients. The ROC analysis showed that the degree of CAS can predict impaired GRPS (AUC = 0.730) and impaired GLPS (AUC = 0.685).ConclusionBesides traditional biochemical indicators, incorporating CAS assessment and CMR assessment of the LV into routine evaluations ensures a more holistic approach to managing MetS patients. Timely intervention of CAS is crucial for improving cardiovascular outcomes in this high-risk population.

Prognostic Value of Left Ventricular Myocardial Strain Parameters Derived from Cardiac Magnetic Resonance Feature Tracking Technique in Light-Chain Cardiac Amyloidosis Patients: A Pilot Study.

Previous research on the prognostic implications of left ventricular myocardial strain using cardiac magnetic resonance feature tracking (CMR-FT) in light-chain cardiac amyloidosis (AL-CA) has shown promising potential. This study aimed to evaluate the prognostic significance of global and segmental left ventricular myocardial strain in AL-CA patients, specifically analyzing the American Heart Association's 16 segments. A total of 75 consecutive patients (50 men, mean age: 55.6 ± 10.0 years) who underwent CMR examination with histologically confirmed systemic AL-CA were retrospectively enrolled between January 2014 and November 2022. Both global and segmental myocardial strain and the American Heart Association's 16 segments were quantified using CMR-FT on the steady-state free precession (SSFP) cine sequence. A comparative analysis was conducted between survivors and non-survivors based on the defined endpoint. Student t-test or Mann-Whitney U, receiver operating characteristic curve, Kaplan-Meier event-free survival curve, and Cox proportional hazards regression were used. Significance was set at p < 0.05. Following a median follow-up of 34 months, 16 out of 75 patients experienced mortality events. B-type natriuretic peptides (BNP) (p < 0.001), global radial strain (RSglobal) (p = 0.033), and RS in the basal inferior segment (RSbas-inferior) (p = 0.025) remained significant as independent predictors of all-cause mortality. The cut-off values were identified as 24.97% for RSglobal, and 20.97% for RSbas-inferior. Kaplan-Meier survival curves revealed significantly reduced event-free survival for individuals in the lower cut-off groups for RSglobal and RSbas-inferior (p = 0.013, p < 0.001, respectively). Radial strain for the global and the basal inferior segment may prove valuable for risk stratification in patients with AL-CA.

Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T CMR feature tracking study

Abstract Purpose Type 2 diabetes mellitus (T2DM) represents the most prevalent form of diabetes, exerting a significant influence on cardiovascular health. Concurrently, metabolic dysfunction-associated fatty liver disease (MAFLD) is closely linked to heightened cardiac dysfunction risk. Our study aimed to explore the additive effect of MAFLD on left ventricular (LV) deformation among T2DM patients, utilizing cardiac magnetic resonance (CMR) feature tracking technology. Methods This study retrospectively included 270 patients with T2DM, comprising 110 individuals with MAFLD and 160 without, alongside 80 age- and sex-matched healthy controls, all of whom underwent CMR examination. Parameters derived from CMR encompass those related to LV function and global strain metrics. LV global strain parameters include global radial peak strain (GRPS), longitudinal peak strain (GLPS), and circumferential peak strain (GCPS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), measured across radial, circumferential, and longitudinal directions. Intergroup analysis, employing the Mann-Whitney U test, was utilized to compare LV function and global strain parameters. Results The LV function parameters, including LV end-diastolic volume (LVEDV), LVEDV index, LV end-systolic volume (LVESV), LVESVI, LV mass, and LV mass index, displayed a progressive augmentation from controls through T2DM patients without MAFLD, to those with MAFLD. In parallel, LVEF showed a declining trajectory across these groups. In contrast, LVSV and LVSVI were comparable among the three groups. In a similar vein, when examining global strain parameters derived from CMR, a significant and progressive deterioration is observed across the groups. GRPS, GCPS and GLPS, along with PSSR and PDSR in radial, circumferential, and longitudinal directions, manifest a pronounced decline moving from control subjects to T2DM patients without MAFLD, and further deteriorating in those with T2DM and MAFLD (All p-values &amp;lt; 0.05). To assess the effect of MAFLD severity on global peak strain, patients with T2DM and MAFLD were stratified into two groups: a mild MAFLD group (N=77) and a moderate to severe MAFLD group (N=33). Although there was a noticeable decline in GRPS, GCPS and GLPS, as well as in PSSR and PDSR across the three groups—from those without MAFLD to those with mild and then moderate to severe MAFLD—the observed differences did not reach statistical significance. The absence of statistical significance is likely due to the small sample sizes of the groups categorized by severity of MAFLD. Conclusions This study revealed that MAFLD has additive worsening effects on LV function and LV global strains in T2DM patients evaluated by CMR. Besides, moderate to severe MAFLD, compared to mild MAFLD, exhibits worse global strain parameters. Early detection and intervention of MAFLD might improve the prognosis of T2DM patients.

Cardiac contractility index, a novel biomarker of incident heart failure amongst people with normal left ventricular ejection fraction in the UK Biobank

Abstract Background Cardiac contractility index (CCI) is a simple non-invasive measure of myocardial contractility defined by systolic blood pressure divided by indexed left ventricular end-systolic volume. Although left ventricular ejection fraction (LVEF) is essential for phenotyping patients with suspected heart failure (HF), it is load dependent and insensitive to subtle subclinical ventricular dysfunction. Left ventricular (LV) strain, although more sensitive at detecting subtle disturbances in myocardial function, also does not reflect loading conditions and dependency on image quality and inter-vendor variability limit widespread use. The ability of CCI to identify patients with subclinical left ventricular dysfunction at risk of developing HF is unknown. Purpose We aimed to: 1) explore the relationship between CCI with conventional imaging biomarkers of LV systolic dysfunction and 2) assess whether CCI could identify those at increased risk of incident HF in people without pre-existing left ventricular dysfunction in the UK Biobank imaging study. Methods We explored the relationship between CCI and laboratory and imaging biomarkers of systolic function, including LVEF and LV strain. Scatter plots were constructed for CCI with LVEF and LV strain. Pearson’s coefficients (r) and coefficient of determination (r2) were calculated to assess for correlations. People with sex-specific thresholds of abnormally low LVEF derived from within the same cohort (&amp;lt;48% for men, and &amp;lt;51% for women) were then excluded. CCI was then dichotomised as being high or low based its median value (4.4 mmHg/ml/m2). Age-sex adjusted Cox proportional hazards ratios (HR) with 95% CIs were estimated for the primary outcome of incident HF (derived from linked national digital registries) in addition to modelling with restricted cubic splines. Results We included 38,215 people (median age 55 years, 48% men). There was moderate correlation between CCI with LVEF (r=0.53 [0.53-0.54], R2=0.29; p&amp;lt;0.001), LV global circumferential strain (r=-0.50 [-0.50- -0.49], R2=0.25; p&amp;lt;0.001) and radial strain (r=-0.49 [0.48-0.50], R2=0.24; p&amp;lt;0.001), although was only weekly correlated with LV global longitudinal strain (r=-0.19 [-0.20- -0.18], R2=0.03; p&amp;lt;0.001) (Figure 1A). Using sex-specific thresholds 33,739 (88.3%) had a normal LVEF. During 195,584 person-years of follow-up (median 5.5 years), a total of 221 (0.7%) participants developed HF. Age-sex adjusted low CCI at baseline was associated with an increased risk of incident HF (adjusted HR 1.33 [1.01-1.75]; p=0.043). The association between CCI and incident HF was curvilinear (Figure 1B). Conclusions CCI identifies people with subclinical left ventricular systolic dysfunction at risk of developing incident heart failure.

Ferroptosis contributes to the development of cardiac dysfunction in iron overload cardiomyopathy

Abstract Background Ferroptosis is a novel form of cell death, and its role in iron overload cardiomyopathy (IOC) has not been elucidated. Purpose To explore whether ferroptosis of cardiomyocytes contributes to cardiac dysfunction in IOC by cardiac MR (CMR) and molecular biology techniques in vivo. Methods A total of 14 Sprague-Dawley (SD) rats were randomly divided into two groups: the control group (n=6) and the IOC group (n=8). The latter was induced by intraperitoneal injection of iron dextran on alternate days for 9 weeks and underwent a 7T CMR for assessment of cardiac function, including left ventricular ejection fraction (LVEF) and global longitude strain (GLS), along with the assessment of iron overload severity and fibrosis using Cine, T2 mapping, and late gadolinium enhancement (LGE), respectively. Circulating iron overload was determined via blood biochemistry analysis, measuring serum iron, ferritin, and transferrin levels. Furthermore, Prussian blue and Masson staining were employed to identify iron and fibrosis deposition within the myocardium, respectively. Cardiac ultrastructure, especially mitochondria, was examined via transmission electron microscopy (TEM). A sensitive fluorescent probe, dihydroethidium (DHE), was employed for the detection of reactive oxygen species (ROS) levels. Malondialdehyde (MDA), prostaglandin-endoperoxide synthase 2 (PTGS2), and glutathione peroxidase 4 (GPX4) were utilized to identify and quantify levels of lipid peroxidation, thereby providing comprehensive insights into cardiac cellular ferroptosis. Results 6 rats survived in the control group and 5 in the IOC group. Compared with the control group, the IOC rats had reduced T2 values of the cardiac septum (P&amp;lt;0.001), with normal LVEF (P&amp;gt;0.05) but decreased GLS (P&amp;lt;0.01), seen in Fig 1A. Based on blood biochemistry and Prussian blue staining, they were evident that IOC rats exhibited both circulating and cardiac iron overload, as seen in Figure 1B, C. Masson staining showed no obvious myocardial fibrosis, which was consistent with negative CMR LGE results, seen in Fig 1A, B. TEM further elucidated cardiac mitochondrial injuries in IOC rats, including focal vacuolization, swelling, crest disruption, and even disappearance, seen in Fig 2A. The fluorescent probe results revealed a striking increase in red fluorescence within the myocardium of IOC rats, seen in Fig 2B. Additionally, IOC rats exhibited significantly elevated levels of MDA and PTGS2mRNA (P&amp;lt;0.001), accompanied by notable downregulation of GPX4mRNA expression (P&amp;lt;0.001), seen in Fig 2C. These findings suggested the occurrence of ferroptosis in the myocardium of IOC rats. Conclusions In IOC, ferroptosis rather than necrosis is the primary driver of cardiac dysfunction, which is characterized by maintaining normal LVEF but experiencing a reduction in GLS without accompanying myocardial fibrosis. Our study sheds light on the potential involvement of ferroptosis in the pathogenesis of IOC.

The Triglycerides - Glucose Index: An independent predictor of late subclinical cardiotoxicity in adult survivors of childhood, adolescent and young adult cancer

Abstract Introduction The Triglycerides - Glucose index (TyG index) has been identified as a reliable alternative for estimating insulin resistance (IR). Numerous recent studies have provided strong statistical evidence suggesting that this index is associated with the development and prognosis of cardiovascular pathologies. Objectives The aim of this study was to investigate the predictive role of the TyG index on the decrease in left ventricular longitudinal global strain (GLS) assessed on two-dimensional echocardiography in asymptomatic adult survivors of childhood, adolescent and young adult cancer. Methods The study included patients aged 18 years and older, asymptomatic cardiovascular survivors of childhood, adolescent and young adult cancer treated with anthracyclines with or without mediastinal radiotherapy. Anthropometric characteristics, cardiovascular risk factors and cancer treatment-related characteristics were collected. The TyG index was calculated using the formula: ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. GLS was assessed and expressed as an absolute value. A GLS equal to 17.3% was retained as the threshold value after calculation in a referent group matched to patients according to age and gender. Cardiac biomarkers GDF 15, ultra-sensitive troponin I and NT-proBNP levels were measured in addition to fasting blood glucose and lipid profiles. Multivariate analysis using linear regression was performed to identify associations between these different parameters. Results A total of 105 cancer survivors from childhood, adolescence and young adulthood were included. The sex ratio was 1.3. The mean age of the patients was 25 years, the mean time since completion of cancer treatment was 10.6 years, the mean cumulative doses of anthracyclines and mediastinal radiotherapy were successively 245.75 ± 75.14 mg/m2 and 34.6 ± 6.19 Gy. Mean GLS was 18.5 ± 2.83%, mean LVEF 60.6 ± 5.69%. None of the patients had any known diabetes or treatment to lower blood glucose or triglyceride levels. No patient had a history of cardiovascular disease. In the univariate study, the factors associated with lower GLS were patient age at recruitment (p = 0.03), mean time since completion of cancer treatment when this was greater than ten years (p = 0.005), dyslipidemia (p = 0.012), obesity (p = 0.037) and TyG (p = 0.037). In multivariate analysis, lower GLS was related to mean time since completion of cancer treatment (p = 0.015) and TyG index (p = 0.002). Conclusion Our results suggest that the TyG index, as a simple and inexpensive marker of insulin resistance, could help identify cancer survivors from childhood, adolescence and young adulthood who would be at risk of subclinical cardiac dysfunction. Prospective studies with larger numbers are needed to confirm these findings.

The transcription factor foxo3 regulates cardiac remodeling after myocardial infarction

Abstract Background Myofibroblast and myeloid cell differentiation following acute myocardial infarction (MI) are important for myocardial fibrosis but also cause adverse remodeling leading to cardiac dysfunction and heart failure. The transcription factor forkhead box O 3 (Foxo3) inhibits hypertrophic cardiac remodeling. We hypothesized that Foxo3, a key regulator of cell differentiation and immunity might inhibit differentiation of fibroblasts and myoloid cells and therefore cardiac fibrosis after MI. Methods MI was induced in Foxo3-/- and wild-type mice by permanent LAD ligation. Cardiac function was determined by transthoracic echocardiography. Cell differentiation was investigated by single nucleus RNA-sequencing (snRNA-seq). Moreover, transdifferentiation assays ex vivo were performed. Results Foxo3-/- mice showed significantly improved survival post- MI (p&amp;lt;0.01) that was in part due to reduced cardiac ruptures (p&amp;lt;0.05). TTE showed reduced LV function, cardiac output, and global strain 4 days post-MI in both groups of animals. However, LV function was significantly attenuated in Foxo3-/- mice 14 d post-MI while diastolic parameters indicated enhanced wall stiffness. snRNA-seq on day 4 post-MI revealed significantly increased numbers of myofibroblasts (p&amp;lt;0.05) transdifferentiating from Progenitor-like state fibroblasts and epicardial derived fibroblasts in Foxo3-/- mice. Myofibroblasts upregulated genes important for extracellular matrix structure and cell migration. Moreover, an upregulation of pro-fibrotic genes was observed in other fibroblast clusters in Foxo3-/- mice and corroborated by significantly elevated collagen type 1 and 3 as well as periostin protein expression. Mechanistically, fibroblasts from Foxo3a-/- mice exhibited enhanced Smad3 dependent myofibroblast marker expression after TGF-ß stimulation. Cell chat analysis indicated enhanced number of interactions and interaction strength of myeloid cells with fibroblasts in Foxo3-/- animals. In line with these observations, differences in cardiac myeloid cell differentiation characterized by reduced center-log ratios of cardiac resident macrophages (Lyve1hiMHCIIlo and Lyve1loMHCIIhi) and increase in monocyte-derived macrophages (Ccr2hi MΦ and Trem2hi MΦ) on day 4 post-MI that was enhanced in Foxo3-/- mice were determined. Differential gene expression patterns on day 4 in pro-inflammatory macrophages (Ccr2hi MΦ) showed upregulation of genes in the interleukin-12 pathway while reparative macrophages (Trem2hi MΦ) revealed an increased expression of genes for extracellular matrix proteins and ECM-collagen interactions in Foxo3-/- mice. Conclusion Our data identify Foxo3 as a master regulator of cardiac remodeling inhibiting myofibroblast and myeloid cell differentiation after acute MI, and suggesting that deficiency of Foxo3 promotes early scar formation but also contributes to adverse matricellular remodeling resulting in impaired cardiac function and enhanced fibrosis.

Left atrial volumetric-mechanical coupling index as a marker of subclinical primary heart involvement in systemic sclerosis

Abstract Background Primary heart involvement in systemic sclerosis (SSc) is a common yet often clinically silent marker of poor prognosis. Up to 80% of patients have histopathological evidence of heart involvement, highlighting the need for better screening and diagnostic methods. N-terminal pro-brain natriuretic peptide (NTproBNP), a well-established cardiac biomarker, is often increased in patients with SSc, but with a not fully understood mechanism. Meanwhile, left atrial volumetric-mechanical coupling index (LACI), a new echocardiographic parameter, has been shown to predict cardiovascular outcomes in heart failure patients and the general population, but it has not been studied in SSc. Purpose To identify new echocardiographic parameters, particularly related to left atrial volume and function, as markers of increased NTproBNP in SSc patients without overt heart involvement. Methods Consecutive SSc patients without overt heart disease referred for routine cardiac screening underwent 2D and 3D transthoracic echocardiography, including atrial and ventricular strain analysis. LACI was calculated by both 2D and 3D echocardiography as the ratio between the left atrial volume index and the tissue-Doppler-imaging septal a’ velocity. Patients with significant structural and functional changes suggestive of systolic or diastolic dysfunction or pulmonary hypertension, and those with impaired global left ventricular strain were excluded. Logistic regression, Pearson correlation coefficients, and area under the receiver-operating characteristic curve (AUC) are used to analyze the association and predictive power of LACI for elevated NTproBNP. Results A total of 36 SSc patients (55±10 years old; 34 (94%) women; mean disease duration 14±11 years) were included. Sixteen (44.4%) had diffuse cutaneous involvement (dcSSc). Seventeen (47%) patients had increased NTproBNP levels (i.e. &amp;gt;125 pg/mL). Among all tested variables, 3D LACI had the best correlation with NTproBNP values (r = 0.63, p&amp;lt;0.001). A 3D LACI of &amp;gt;2 associated with NTproBNP of &amp;gt;125 pg/mL (odds ratio 7.33 [95%CI 1.38-38.8]; p=0.01) and predicted these increased values with a sensitivity of 76.9% and a specificity of 81.2% (AUC 0.78). NTproBNP was also correlated with 2D LACI (r=0.55, p&amp;lt;0.001), peak left atrial longitudinal strain (r=-0.42, p=0.01), and left atrial contraction strain (r=0.48, p=0.005). Compared to patients with limited cutaneous involvement, those with dcSSc had higher NTproBNP values (250±139.6 vs 107.2±110.9 pg/mL, p=0.001), higher 3D LACI values (2.6±0.9 vs 1.9±0.5, p=0.02), with similar left atrial and ventricular strain parameters. Conclusion Left atrial volumetric-mechanical coupling index assessed by 3D echocardiography is significantly associated with and predictive of elevated NTproBNP levels in SSc patients without overt heart disease and may be a potentially useful non-invasive marker for screening for early subclinical heart involvement in SSc patients.

Evaluation of Fetal Heart Using Fetal Heart Quantification (fetalHQ) Technique in an Indian Cohort.

To evaluate the intra- and interobserver reproducibility of parameters used to determine cardiac morphometry and deformation using FetalHQ in Indian population. Two operators blinded to each other performed FetalHQ analysis independently on 35 normal fetuses of gestational age between 18 + 0 and 37 + 0 weeks and days. Intra- and interobserver correlation coefficient and limits of agreement were ascertained for parameters obtained from HQ analysis. Excellent reproducibility (ICC > 0.9) was observed for global morphometric parameters. Ejection fraction, stroke volume, stroke volume/kg demonstrated excellent reliability (ICC > 0.9), cardiac output, fractional area change showed a lower correlation (ICC < 0.8), and right and left ventricular global strain showed no correlation. Twenty-four segment sphericity index of left ventricle (LV) and right ventricle (RV) showed low to moderate correlation (LV-ICC 0.48-0.79; RV-ICC 0.43-0.82). Fractional shortening (FS) showed poor intraobserver reliability in RV. FetalHQ provides reliable estimates of the global cardiac morphometry but not for global cardiac strain. Regional transverse contractility represented by FS has poor correlation in right ventricle, especially in the apical region, possibly due to moderator band. Nevertheless, it is a promising tool which requires technical advancements and validation to improve its accuracy and reliability.

Assessment of Biventricular Systolic and Diastolic Function Using Conventional and Strain Echocardiography in Children with Sickle Cell Disease Surviving 1-year After Hematopoietic Stem Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for children with sickle cell disease (SCD). The effects of HSCT on ventricular function are not well characterized in children with SCD. Echocardiograms from children with SCD who underwent HSCT between 2007 and 2017 were retrospectively analyzed before and 1-year after HSCT. Left ventricular (LV) volumes, mass, and ejection fraction were calculated by the 5/6 area*length method. LV end-diastolic and systolic dimensions, septal, and posterior wall thickness, and fractional shortening were measured by M-mode. Mitral and tricuspid inflow Dopplers (E and A waves) as well as mitral, tricuspid, and septal tissue Dopplers (E', A') were assessed. E/A, E'/A' and E/E' ratios were calculated. Biventricular strain imaging was performed using speckle-tracking echocardiography. Peak global systolic longitudinal and circumferential LV strain, and global longitudinal right ventricular strain, as well as early and late diastolic strain rate, were measured on LV apical 4-chamber, LV short-axis mid-papillary, and RV apical views, respectively. Forty-seven children (9.7 ± 5.5years, 60% male) met inclusion criteria. Pre-HSCT, subjects had mild LV dilation with normal LV systolic function by conventional measure of ejection fraction and fractional shortening. There was a significant reduction in LV volume, mass, and ejection fraction after HSCT, but measurements remained within normal range. LV longitudinal and circumferential strain were normal pre-HSCT and showed no significant change post-HSCT. RV strain decreased after HSCT, but the absolute change was small, and mean values were normal both pre- and post-HSCT. Conventional measures of diastolic function were all normal pre-HSCT. Post-HSCT there was a reduction in select parameters, but all parameters remained within normal range. Early and late diastolic strain rate parameters showed no significant change from pre- to post-HSCT. At one-year after HSCT in children with SCD conventional measures of systolic and diastolic function are within normal limits. Except for a small decrease in RV systolic strain with values remaining within normal limits, systolic strain and diastolic strain rate values did not significantly change 1-year after HSCT.

Clinical Implications of Left Ventricular Apex Mechanics in Patients With Apical Hypertrophic Cardiomyopathy

Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathologic hypertrophy mainly at the left ventricular (LV) apex. Although previous studies have indicated apical dysfunction in ApHCM, how apical mechanics change during disease progression has not been thoroughly examined. The aims of this study were to characterize the mechanics of the LV apex in patients with ApHCM at different disease stages and to explore the clinical significance of these alterations. One hundred four patients with ApHCM were divided into three subtypes on the basis of LV apical maximum wall thickness (AMWT) and extent of hypertrophy: relative type (isolated apical hypertrophy with AMWT<15mm), pure type (isolated apical hypertrophy with AMWT≥15mm), and mixed type (both apical and midventricular hypertrophy with AMWT≥15mm). Two-dimensional speckle-tracking echocardiography was used to analyze LV segmental strain, global strain, and twist. Comparisons of these parameters were performed among ApHCM subtypes and 30 healthy control subjects. Logistic regression and Cox proportional-hazards regression analyses were used to explore associations between myocardial mechanics and clinical indicators. A composite outcome of new-onset atrial fibrillation, heart failure hospitalization, myectomy, and all-cause mortality was assessed. Even in relative ApHCM patients, apical longitudinal strain (LS), circumferential strain, and radial strain (RS) were significantly impaired compared with control subjects (LS: -14.6±4.1% vs -20.0±1.7% [P=.001]; circumferential strain: -19.6±2.5% vs -25.6±3.7% [P=.002]; RS: 26.6±7.4% vs 35.6± 11.1% [P=.026]), while apical rotation and LV twist remained unchanged. In patients with greater apical hypertrophy (mixed and pure patients), apical LS and RS were more abnormal. Moreover, apical rotation showed significant reductions compared with relative-type patients. After adjusting for clinical and myocardial mechanical parameters, apical rotation was independently associated with New York Heart Association functional class≥II (odds ratio, 0.81; 95% CI, 0.66-0.99; P=.036) and the composite outcome (hazard ratio, 0.82; 95% CI, 0.73-0.91; P=.001). Relative ApHCM demonstrates apical dysfunction but sparing of apical rotation, which was abnormal in more extensive phenotypes. LV apex mechanics were closely related to clinical patterns, with apical rotation correlated with both New York Heart Association functional class≥II and clinical events.

Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy

BackgroundAficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study. ObjectivesThe authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM. MethodsSerial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF). ResultsAmong 282 patients (mean age 59 ± 13 years; 41% female, 79% White, 19% Asian), mean LVEF was 75% ± 6% with resting and Valsalva LVOT gradients of 55 ± 30 mm Hg and 83 ± 32 mm Hg, respectively. Over 24 weeks, aficamten significantly lowered resting and Valsalva LVOT gradients, and improved left atrial volume index, lateral and septal eʹ velocities, and lateral and septal E/eʹ (all P ≤ 0.001). LV end-systolic volume increased and wall thickness decreased (all P ≤ 0.003). Aficamten resulted in a mild reversible decrease in LVEF (−4.8% [95% CI: −6.4% to −3.3%]; P < 0.001) and absolute LV global circumferential strain (−3.7% [95% CI: 1.8%-5.6%]; P < 0.0010), whereas LV global longitudinal strain was unchanged. Several measures, including LVEF, LVOT gradients, and E/eʹ returned to baseline following washout. Among those treated with aficamten, improved pVO2 and reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP) were associated with improvement in lateral eʹ velocity and septal and lateral E/eʹ (all P < 0.03), whereas improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (KCCQ-CSS) was associated with a decrease in both LVOT gradients (all P < 0.001). ConclusionsCompared with placebo, patients receiving aficamten demonstrated significant improvement in LVOT gradients and measures of LV diastolic function, and several of these measures were associated with improvements in pVO2, KCCQ-CSS, and NT-proBNP. A modest decrease in LVEF occurred yet remained within normal range. These findings suggest aficamten improved multiple structural and physiological parameters in oHCM without significant adverse changes in LV systolic function. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818)

Abstract P325: Additive effect of nighttime blood pressure on left ventricular strain in patients with primary aldosteronism evaluated via cardiac magnetic resonance tissue tracking

Background: Primary aldosteronism (PA) induces left ventricular (LV) remodeling and increases the risk of high nighttime blood pressure (BP), which causes further heart damage. This study aimed to investigate whether nighttime BP aggravates LV deformation dysfunction and to identify independent factors affecting the global peak strain (PS) of LV remodeling in patients with PA compared to patients with essential hypertension (EH). Methods: A total of 280 patients with PA and 280 age- and sex-matched patients with EH who underwent cardiac magnetic resonance examination at the First Affiliated Hospital of Chengdu Medical College were included. According to the results of adrenal computed tomography and/or adrenal venous sampling, there were 154 patients with aldosterone-producing adenoma (APA) and 126 patients with idiopathic hyperaldosteronism (IHA). Twenty-four-hour ambulatory BP monitoring (ABPM), LV function, global strain parameters, and other clinical medical data were compared, and multivariate analysis was performed to identify the independent indicators of the LV PS. Results: No differences in age, sex, body mass index, clinical BP, 24-h mean BP, daytime BP, or duration of hypertension were found between the groups. Nighttime systolic BP (132 ± 17 vs. 126 ± 18 mm Hg, P &lt; 0.05) and diastolic BP (85 ± 11 vs. 80 ±10 mm Hg, P &lt; 0.05) were greater in PA patients than in EH patients. Compared with the EH controls, the PA patients had a lower LV global PS and peak diastolic strain rate (PDSR) in three directions. No significant differences were found in the PS (radial or longitudinal) or PDSR in the three directions between the APA and IHA groups. Furthermore, nighttime BP was an independent predictor of LV global radial, circumferential, and longitudinal PS. Conclusions: High nighttime BP may aggravate LV stiffness in patients with PA, resulting in decreased LV strain and function. Nighttime BP was independently correlated with LV global PS in patients with PA.

Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T cardiac magnetic resonance feature tracking study

BackgroundType 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR).MethodsData of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain.ResultsOur investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values.ConclusionsThis study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD’s adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.

Myocardial strain is regulated by cardiac preload in the early stage of sepsis

BackgroundOwing to a lack of data, this study aimed to explore the effect of cardiac preload on myocardial strain in patients with sepsis.MethodsA total of 70 patients with sepsis in intensive care unit (ICU) of a tertiary teaching hospital in China from January 2018 to July 2019 and underwent transthoracic echocardiography were enrolled. Echocardiographic data were recorded at ICU admission and 24 h later. Patients were assigned to low left ventricular end-diastolic volume index (LVEDVI) and normal LVEDVI groups. We assessed the impact of preload on myocardial strain between the groups and analyzed the correlation of echocardiographic parameters under different preload conditions.ResultsThirty-seven patients (53%) had a low LVEDVI and 33 (47%) a normal LVEDVI. Those in the low LVEDVI group had a faster heart rate (121.7 vs. 95.3, p < 0.001) and required a greater degree of fluid infusion (3.67 L vs. 2.62 L, P = 0.019). The left ventricular global strain (LVGLS) (-8.60% vs. -10.80%, p = 0.001), left ventricular global circumferential strain (LVGCS) (-13.83% vs. -18.26%, p = 0.006), and right ventricular global longitudinal strain (RVGLS) (-6.9% vs. -10.60%, p = 0.001) showed significant improvements in the low LVEDVI group after fluid resuscitation. However, fluid resuscitation resulted in a significantly increased cardiac afterload value (1172.00 vs. 1487.00, p = 0.009) only in the normal LVEDVI group. Multivariate backward linear regression showed that LVEDVI changes were independently associated with myocardial strain-related improvements during fluid resuscitation. The baseline LVEDVI was significantly negatively correlated with the LVGLS and RVGLS (r = -0.44 and − 0.39, respectively) but not LVGCS. LVEDVI increases during fluid resuscitation were associated with improvements in the myocardial strain degree.ConclusionsMyocardial strain alterations were significantly influenced by the cardiac preload during fluid resuscitation in sepsis.