Left Ventricular Structural Remodeling Research Articles

Liver fibrosis is associated with left ventricular remodeling: insight into the liver-heart axis.

In nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers. In this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden. Between November 2017 and July 2018, participants underwent MRI at 1.5 Tesla for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography), left ventricular (LV) structure and function, as well as myocardial native T1 mapping. We analyzed 278 circulating cardiovascular biomarkers using a Bayesian statistical approach. In total, 92 participants were enrolled (mean age 59.5 ± 4.6 years, 32 women). The mean liver stiffness was 2.1 ± 0.4 kPa. 53 participants displayed hepatic steatosis. LV concentricity increased across quartiles of liver stiffness. Neither liver fat nor liver stiffness displayed any relationships to myocardial tissue characteristics (native T1). In a regression analysis, liver stiffness was related to increased LV concentricity. This association was independent of diabetes and liver fat (Beta = 0.26, p = 0.0053), but was attenuated (Beta = 0.17, p = 0.077) when also adjusting for circulating levels of interleukin-1 receptor type 2. MRI reveals that liver fibrosis is associated to structural LV remodeling, in terms of increased concentricity, in participants from the general population. This relationship could involve the interleukin-1 signaling. Liver fibrosis may be considered a cardiovascular risk factor in patients without cirrhosis. Further research on the mechanisms that link liver fibrosis to left ventricular concentricity may reveal potential therapeutic targets in patients with non-alcoholic fatty liver disease (NAFLD). Previously, studies on liver fibrosis and cardiac remodeling have focused on advanced stages of liver fibrosis. Liver fibrosis is associated with left ventricular (LV) concentricity and may relate to interleukin-1 receptor type 2. Interleukin-1 signaling is a potential mechanistic interlink between early liver fibrosis and LV remodeling.

Left Ventricular Dilation Resulting from the Absence of Either Rgs2 or Rgs5 Is Associated with Increased Immune Cell Infiltration in the Myocardium

Sustained sympathoexcitation is a hallmark of heart failure, with equally sustained activation of downstream signaling pathways involving Gs- and Gi/o-coupled β-adrenergic receptors (βAR) stimulating cAMP production and PKA activation. A critical mechanism controlling G protein-mediated βAR signaling is the activity of regulator of G protein signaling (RGS) proteins, including members of the B/R4 subfamily, which accelerate the termination of Gq/11 and Gi/o protein signaling. Previous studies by us and others reported that moderation of Gi/o activity separately by RGS2 and RGS5 of the R4 subfamily is key to maintaining normal ventricular rhythm. The loss of one or both R4 RGS proteins also results in left ventricular (LV) dilation and reduced ejection fraction. Here, we tested the hypothesis that the LV structural remodeling is due to the disruption of the coordinated activity of RGS2 and 5 resulting in sensitization of βAR signaling. To test this hypothesis, we challenged wild type (WT), Rgs2 KO ,Rgs5 KO, and Rgs2/5 double knockout (dbKO) adult male mice with sub-chronic infusion of isoproterenol (ISO, 30 mg/kg/day, 3 days) via a peritoneal osmotic minipump implantation. Rgs2 KO and Rgs5 KO mice showed increased LV chamber size at baseline, which was unchanged by ISO administration. In saline-treated animals, the loss of Rgs2 increased Rgs5 mRNA expression, while Rgs5 absence increased Rgs4 mRNA expression. ISO infusion induced concentric cardiac hypertrophy in WT mice, as evidenced by increased heart weight/tibia length (HW/TL) ratio and cardiomyocyte cross sectional area. While ISO infusion increased interstitial fibrosis in midventricular tissue and HW/TL ratio in dbKO mice, it did not affect cardiomyocyte cross sectional area or exacerbate LV dilation, despite increased expression of the cardiac fetal gene Nppa as well as the sarcomeric protein α-actinin and Ca2+/calmodulin-dependent kinase II (CaMKII). Cardiact tissue from saline-treated Rgs2 KO and Rgs5 KO mice had markedly increased CD45+ cells vs WT, while tissue from Rgs5 KO mice showed increased CD68+ cells, as revealed by immunohistochemistry. Taken together, these results indicate that ventricular remodeling seen in Rgs2 KO, Rgs5 KO, and Rgs2/5 dbKO mice is insensitive to sustained βAR stimulation but may be due to increased cardiac resident immune cell population. This work was supported by NIH R56 DK132859-01A1 and R01 HL139754, and Craig H. Neilsen Foundation Grant 382566 to Patrick Osei-Owusu. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Macrophage Polarization in Left Ventricular Structural Remodeling Induced by Hypertension

Macrophage Polarization in Left Ventricular Structural Remodeling Induced by Hypertension

Sacubitril/Valsartan Alleviates Cardiac Remodeling and Dysfunction in L-NAME-Induced Hypertension and Hypertensive Heart Disease.

There is ample evidence on the benefit of angiotensin receptor-neprilysin inhibitors (ARNIs) in heart failure, yet data regarding the potential protective action of ARNIs in hypertensive heart disease are sparse. The aim of this study was to show whether an ARNI exerts a protective effect in a model of Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension with a hypertensive heart and to compare this potential benefit with an angiotensin-converting enzyme inhibitor, captopril. Five groups of adult male Wistar rats were studied (14 per group) for four weeks: untreated controls; ARNI (68 mg/kg/day); L-NAME (40 mg/kg/day); L-NAME treated with ARNI; and L-NAME treated with captopril (100 mg/kg/day). L-NAME administration induced hypertension, accompanied by increased left ventricular (LV) weight and fibrotic rebuilding of the LV in terms of increased concentration and content of hydroxyproline in insoluble collagen and in total collagen and with a histological finding of fibrosis. These alterations were associated with a compromised systolic and diastolic LV function. Treatment with either an ARNI or captopril reduced systolic blood pressure (SBP), alleviated LV hypertrophy and fibrosis, and prevented the development of both systolic and diastolic LV dysfunction. Moreover, the serum levels of prolactin and prolactin receptor were reduced significantly by ARNI and slightly by captopril. In conclusion, in L-NAME-induced hypertension, the dual inhibition of neprilysin and AT1 receptors by ARNI reduced SBP and prevented the development of LV hypertrophy, fibrosis, and systolic and diastolic dysfunction. These data suggest that ARNI could provide protection against LV structural remodeling and functional disorders in hypertensive heart disease.

Assessment of LV structural remodelling by the application of the finite element method to 3D echocardiography data

ABSTRACT This study presents novel applications for conducting left ventricular (LV) shape analysis within a finite element (FE) framework. The 3D endocardial surface data of both healthy and dilated LVs are obtained using TomTec 4D LV-Analysis software through echocardiography and then imported into the FE framework for LV geometry. By applying FE analysis to 3D echocardiography data, we propose novel methods for evaluating LV shape and remodelling, including the nodal strain approximation along myocardial fibre directions, the assessment of LV sphericity and eccentricity in multiple planes, a new method for LV apical conicity, and the analysis of regional LV rotations. The feasibility of these novel formulations and the developed FE based framework are demonstrated by evaluating and comparing 3D echocardiography data from two objects, one with a healthy LV and the other with dilated cardiomyopathy.

Association of left ventricular structural remodeling types with fibronectin deficiency in patients with multivessel coronary artery disease

Aim. To evaluate the serum fibronectin level in patients with multivessel coronary artery disease, and to identify the relationship of fibronectin level with atrial fibrillation (AF) developed in the hospital after coronary artery bypass grafting (CABG) and types of left ventricular (LV) structural remodeling.Material and methods. This prospective observational study of 80 patients after elective CABG at the Cardiac Surgery Department № 1 of the N.V. Sklifosovsky Research Institute for Emergency Medicine from October 2020 to May 2022. The groups were divided depending on the development of AF after CABG surgery (19 patients with AF developed in the hospital after CABG (up to 10 days), 61 patients — control group). All patients underwent a general clinical examination and transthoracic echocardiography, with estimation of left ventricular remodeling type. Serum fibronectin level was determined by enzyme immunoassay using the Fibronectin agent (Technozym, Austria).Results. The median fibronectin values in the group with AF was 110,10 [86,86; 134,00] mcg/ml versus 120,90 [92,01; 161,50] µg/ml of the comparison group (p=0,19). The following LV patterns were observed: normal LV geometry (NLVG) — in 1 patient (5,26%), concentric LV remodeling (CLVR) — in 3 patients (15,79%), concentric LV hypertrophy (CLVH) — in 10 patients (52,63%), eccentric LV hypertrophy (ELVH) — in 5 patients (26,32%). In the group without AF, 25 patients (40,98%) were diagnosed with NLVG, 26 patients (42,62%) — CLVR, 6,56% (n=4) — CLVR, while ELVH was diagnosed in 6 patients (9,84%). Differences in geometry types between groups were significant (p<0,0001). Multivariate analysis adjusted for gender, age, cardiopulmonary bypass time, the predictive value remained for CLVH — odds ratio 15,83 (95% confidence interval, 4,082-1,442,00; p=0,0001) and ELVH — odds ratio 5,17 (95% confidence interval, 1,365-19,573; p=0,015). A further study showed that fibronectin <116,496 µg/ml with a sensitivity of 78% and specificity of 53% is associated with CLVH (p=0,006) in patients of both groups.Conclusion. Fibronectin <116,496 µg/ml is associated with CLVH in patients with multivessel coronary artery disease (sensitivity 78%, specificity 53%; p=0,006).

Left ventricular twist in patients with severe aortic stenosis: meaning and evolution after surgery

Abstract Background Structural and functional left ventricular (LV) remodeling is the result of myocardial adaptation to chronic pressure overload in patients with severe aortic stenosis (AS). Changes in LV rotational dynamics are supposed to occur due to increased afterload in order to maintain LV ejection fraction (EF) in this setting. However, data regarding rotational dynamics with AS severity and their evolution after aortic valve replacement (AVR) are scarce. Goal To describe LV twist in patients with severe AS according to LV remodeling and assess its evolution after surgical AVR. Methodology Single center prospective cohort study of patients with classical isolated severe AS referred to surgical AVR. Complete transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) were performed before surgery for both valvular and LV remodeling assessment. TTE was performed at the 3rd to 6th post-operative month. LV twist was defined as the peak difference in systolic rotations of LV apex and base as viewed from the apex and calculated at bidimensional strain in short axis views. LV remodeling was categorized by CMR according to Figure 1. Correlation analysis was performed for indexes of AS severity and LV function. Results A total of 80 patients with classical high flow, high gradient, preserved LV EF (46% male; mean age 71 ± 8 years old; mean aortic valve [AV] gradient 61±17.6mmHg, mean AV area 0.73±0.18cm2 , mean LVEF: 58 ± 9%) were included. LV twist before surgery was 24.5 +/- 9.7% and this was modestly correlated with both LV flow (r = 0.315, p= 0.001) and AV gradients (r = 0.315, p = 0.013). Rotational indexes were no different across distinct types of LV remodeling. After AVR there was a significant decrease in LV twist (24.5 +/- 9.7% vs. 16.5 +/- 8.3%, p<0.001), despite significant improvement in global longitudinal strain (-14.7 ± 3.9% vs -16.1 ± 3.1%, p < 0.001) and maintenance of preserved LVEF (58 ± 9% vs 60 +/- 8%, p = 0.07). Conclusion As LV twist has an inverse relation to GLS after AVR, this may represent a compensatory mechanism for LVEF preservation in patients with severe AS. Rotational mechanics seems to be independent from structural LV remodeling in this setting.

Cumulative accelerometer-based sedentary time from childhood through young adulthood with progressive left ventricular remodelling in British youth: a 13-year longitudinal study

Abstract Background Questionnaire-based sedentary time and behaviour has been associated with worse cardiometabolic profiles such as adiposity, insulin resistance, and blood pressure, in the pediatric population. However, objectively measured sedentary time has not been consistently associated with poor cardiometabolic health. Till date, there is no evidence of the cumulative effect of time spent sedentary assessed with an accelerometer and cardiac structural changes in youth. Purpose To investigate the longitudinal association of cumulative sedentary time from childhood through young adulthood with structural cardiac changes during growth from adolescence through young adulthood. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 766 children aged 11 years who had at least two follow-up time-points accelerometer-measured sedentary time over 13 years follow-up, and complete cardiac structural measures at age 17 years clinic visit were included. Sedentary time was assessed with ActiGraph accelerometer worn for 4-7 days at the 11-, 15-, and 24-year clinic visits. Repeated echocardiography measured left ventricular mass indexed for height2.7 (LVMI2.7) and relative wall thickness (RWT) were available at baseline and follow-up. Multivariable adjusted associations were examined using generalized linear mixed-effect models and adjusted for sex, and time-varying covariates measured at both baseline and follow-up such as age, insulin, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, glucose, fat mass, lean mass, smoking status, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, light physical activity, and moderate to vigorous physical activity, Results Among 766 children (mean [SD] age, 11.75 [0.24] years; 422 [55.0%] females]) males spent on average 360, 467, and 527 minutes/day sedentary at ages 11, 15, and 24 years, respectively. Females spent 364, 481, and 535 minutes/day sedentary at ages 11, 15, and 24 years respectively. LVMI2.7 was significantly higher among males than females with an average difference of ∼4g/m2.7 both at ages 17 and 24 years but no significant sex differences in RWT. In a fully adjusted model, a 1-minute increase in sedentary time from ages 11 – 24 years was associated with progressively increased changes in LVMI2.7 (effect estimate 0.004g/m2.7 [CI 0.001 – 0.006] p=0.002) from ages 17 – 24 years in the total cohort and females (effect estimate 0.009g/m2.7 [CI 0.005 – 0.012] p<0.0001). There was no statistically significant longitudinal association between cumulative sedentary time and changes in RWT in the total cohort, males, and females. Conclusion Cumulative increase in sedentary time during growth from childhood through young adulthood was associated with progressive left ventricular structural remodelling.

The change in propagation speed of natural shear waves by altering preload might differentiate patients with increased myocardial stiffness

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders - FWO. Background Shear wave (SW) elastography (SWE) is a novel ultrasound-based technique for the assessment of myocardial stiffness. SWE tracks the propagation of SWs travelling through the myocardium, induced by e.g. mitral valve closure (MVC). The speed of SWs is related to myocardial stiffness. As myocardial stiffness is defined by a non-linear stress-strain relation, it is dependent on the operating stress levels and thus left ventricular (LV) loading. As a result, elevated SW speed values could be caused by both increased LV preload or structural remodelling of the myocardium. In this way, performing SWE measurements at different loading states could potentially provide additional information aiding with the interpretation of these measurements. Purpose to investigate if performing SWE before and after a loading change could provide more information on tissue properties of the myocardium. Methods Twelve patients [age: 76(41–82)] receiving intermittent hemodialysis (HD) and 12 age-matched healthy volunteers [age: 67(47–71); p = 0.19] were included. Patients were scanned before and 1 hour after the start of HD. Parasternal long-axis views were acquired using an experimental ultrasound scanner with an average frame rate of 1086±185 Hz. Patients were divided into 2 equal groups based on the grade of diastolic dysfunction (DD), determined using conventional echo parameters (group 1: DD grade 0–1 and group 2: DD grade 2−3). SWs after MVC were visualized on M-mode maps along the septum which were colour coded for tissue acceleration (Figure A). The speed was semi-automatically calculated by measuring the slope of the SW. Results The average ultra-filtrated volume after 1h of HD was 0.64±.27 L, which did not significantly differ between patient groups (p = 0.44). Patients in group 2 had significantly higher indexed LV wall mass compared to group 1 (128±39 g/m² vs. 72±24 g/m²; p = 0.02), indicative of LV structural remodelling. SW speed after MVC was significantly different between healthy volunteers and the patient groups at baseline (p<0.01) (Figure B). After 1h of HD, SW speed decreased in both groups, with the largest decrease in group 2 (Figure B). Furthermore, SW speed values of patient group 1 decreased to values similar to healthy volunteers, while patient group 2 still had significantly increased SW propagation speed. Conclusions Overall, myocardial stiffness, assessed using SW propagation speed, of patients with end-stage kidney disease was increased compared to healthy volunteers. This could result from increased LV preload or structural remodelling. Our data indicate that in addition to single measurements, assessing the change in SW speed by altering the loading state might aid in differentiating these causal mechanisms underlying increased myocardial stiffness. Therefore, adding a loading challenge, e.g. leg lifting, when doing SWE could provide additional information. Further research needs to confirm these initial findings.

Sex Differences in Type 2 Diabetes Mellitus-Related Left Ventricular Remodeling: A Cardiovascular Magnetic Resonance Study.

Background The purpose of this study was to evaluate the sex differences in myocardial structure, tissue characteristics, and myocardial function in type 2 diabetes mellitus (T2DM) patients. Methods A total of 62 T2DM patients and 40 controls were prospectively recruited for the study. All the participants were scanned using cardiovascular magnetic resonance (CMR) cine and underwent native and postcontrast T1 mapping to obtain left ventricular (LV) structure, function, and tissue characteristics. The differences between the control and T2DM patients were compared in males and females, respectively. Results For myocardial structure, T2DM was associated with a larger ratio of myocardial mass to end-diastolic volume (MVR, T2DM: 0.87 ± 0.20 vs. controls: 0.73 ± 0.14, p = 0.008) and thicker wall thickness (WT, T2DM: 6.5 ± 1.1 mm vs. controls: 5.6 ± 1.0 mm, p = 0.002) in females. For tissue characteristics, T2DM was associated with a similar T1 value, elevated extracellular volume fraction (ECV, T2DM: 27.8 ± 3.6% vs. controls: 25.1 ± 2.5%, p = 0.002), and increased extracellular matrix volume index (ECMVi, T2DM: 15.8 ± 3.8 ml/m2 vs. controls: 13.4 ± 2.7 ml/m2, p = 0.008) in males. For myocardial function, in male, compared with control, T2DM was associated with decreased peak longitudinal diastolic strain rate (PLDSR, T2DM: 0.97 ± 0.19 1/s vs. control: 1.13 ± 0.29 1/s, p = 0.030). Conclusions There might be sex differences in myocardial remodeling induced by T2DM, including LV structural concentric remodeling in female patients and extracellular matrix remodeling and subclinical diastolic dysfunction in male patients.

Evaluation of the effectiveness of the chronic heart failure therapy using the device cardiac contractility modulation according to the new non-invasive method of the myocardium work analysis

Aim To analyze echocardiographic parameters that reflect left ventricular (LV) myocardial contractility, using a novel method for evaluation of myocardial performance in patients with chronic heart failure (CHF) and atrial fibrillation (AF) during heart contractility modulation (HCM).Material and methods Standard echocardiographic parameters and indexes of myocardial strain and work were analyzed for 66 patients (52 men and 14 women; median age, 60 [54; 66] years). 36 patients had paroxysmal AF and 30 patients had permanent AF. All patients had CHF with a duration of 17 [4; 60] months; duration of AF was 12 [6; 36] months. At baseline, the left ventricular ejection fraction (LV EF) was 33 [27; 37] %.Results After one year of HCM, LV EF significantly increased from 33 [27; 37] to 38 [33; 44] % (р=0.001). Also, there were improvements in the myocardial global longitudinal strain (from -6.00 [ - 8; - 4] to -8 [ - 10; - 6] %; р=0.001) and parameters of myocardial work, including the global work efficiency (from 74 [65; 79] to 80 [73; 87] mm Hg%; р=0.001), global constructive work (from 699 [516; 940] to 882 [714; 1242] mm Hg%; р=0.001), and global myocardial work index (from 460 [339; 723] to 668 [497; 943] mm Hg%; р=0.001). A segmentary analysis of LV work parameters showed positive changes in the myocardial constructive work in the area of the interventricular septal apical segment (at baseline, 844 [614; 1224]; after HCM, 1027 [800; 1520] mm Hg%; р=0.05) and the medium segment of the LV anteroseptal wall (at baseline, 593 [312; 1000]; after HCM, 877 [494; 1145] mm Hg%; р=0.05).Conclusion This method for analysis of the myocardial work provides a more detailed examination of LV structural and functional remodeling and mechanisms for its effects on the LV contractile function in patients with CHF. This method is promising and merits further study in various clinical situations.

Abstract 13007: Change in QRS 3D Voltage Time Integral (3D QRS Area) Predicts Left Ventricular Reverse Remodeling in Sacubitril-Valsartan Treated Patients With Left Bundle Branch Block

Introduction: The instantaneous absolute 3D ECG voltage integrated over the duration of QRS (VTI QRS-3D ) is an improved marker of left ventricular (LV) electrical dyssynchrony compared to QRS duration (QRSd). Among patients with left bundle branch block (LBBB) receiving heart failure medical therapy, the relationship between electrical remodeling assessed by VTI QRS-3D and structural LV remodeling is unclear. Hypothesis: Reduction in VTI QRS-3D is correlated with left ventricular reverse remodeling. Methods: We retrospectively studied heart failure patients with underlying LBBB who were treated with sacubitril-valsartan for ≥3 months between January 2014 - June 2019. Echocardiograms and 12-lead ECGs were collected pre and post sacubitril-valsartan treatment. ECGs were converted to orthogonal X, Y, Z leads using Kors matrix, to then obtain VTI QRS-3D . Echocardiographic LV measures included end-diastolic volume (LVEDV), end-systolic volume (LVESV) and ejection fraction (LVEF). We calculated the Pearson correlations between electrical variables and changes in echocardiographic measures pre to post treatment. Results: We included 56 patients (mean age 64.0±13.5 years, men 53.6%, baseline LVEF 25.2±9.1%). ΔVTI QRS-3D was strongly correlated with improvement in all 3 echocardiographic measures (all p ≤0.01). ΔVTI QRS-3D outperformed ΔQRSd in predicting echocardiographic response (Table). Conclusions: In heart failure patients with LBBB on medical therapy, electrical remodeling assessed as reduction in VTI QRS-3D is strongly predictive of LV structural and functional reverse remodeling.

Clec4e-Receptor Signaling in Myocardial Repair After Ischemia-Reperfusion Injury

The bacterial C-type lectin domain family 4 member E (CLEC4E) has an important role in sterile inflammation, but its role in myocardial repair is unknown. Using complementary approaches in porcine, murine, and human samples, we show that CLEC4E expression levels in the myocardium and in blood correlate with the extent of myocardial injury and left ventricular (LV) functional impairment. CLEC4E expression is markedly increased in the vasculature, cardiac myocytes, and infiltrating leukocytes in the ischemic heart. Loss of Clec4e signaling is associated with reduced acute cardiac injury, neutrophil infiltration, and infarct size. Reduced myocardial injury in Clec4e -/- translates into significantly improved LV structural and functional remodeling at 4weeks' follow-up. The early transcriptome of LV tissue from Clec4e -/- mice versus wild-type mice reveals significant upregulation of transcripts involved in myocardial metabolism, radical scavenging, angiogenesis, and extracellular matrix organization. Therefore, targeting CLEC4E in the early phase of ischemia-reperfusion injury is a promising therapeutic strategy to modulate myocardial inflammation and enhance repair after ischemia-reperfusion injury.

Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure.

Myocardial sodium-glucose cotransporter 1 (SGLT1) has been shown to be upregulated in humans with heart failure (HF) with or without diabetes. In vitro studies have linked SGLT1 to increased nitro-oxidative stress in cardiomyocytes. We aimed to assess the relation between left ventricular (LV) SGLT1 expression and the extent of nitro-oxidative stress in two non-diabetic rat models of chronic heart failure (HF) evoked by either pressure (TAC, n = 12) or volume overload (ACF, n = 12). Sham-operated animals (Sham-T and Sham-A, both n = 12) served as controls. Both TAC and ACF induced characteristic LV structural and functional remodeling. Western blotting revealed that LV SGLT1 protein expression was significantly upregulated in both HF models (both p < 0.01), whereas the phosphorylation of ERK1/2 was decreased only in ACF; AMPKα activity was significantly reduced in both models. The protein expression of the Nox4 NADPH oxidase isoform was increased in both TAC and ACF compared with respective controls (both p < 0.01), showing a strong positive correlation with SGLT1 expression (r = 0.855, p < 0.001; and r = 0.798, p = 0.001, respectively). Furthermore, SGLT1 protein expression positively correlated with the extent of myocardial nitro-oxidative stress in failing hearts assessed by 3-nitrotyrosin (r = 0.818, p = 0.006) and 4-hydroxy-2-nonenal (r = 0.733, p = 0.020) immunostaining. Therefore, LV SGLT1 protein expression was upregulated irrespective of the nature of chronic hemodynamic overload, and correlated significantly with the expression of Nox4 and with the level of myocardial nitro-oxidative stress, suggesting a pathophysiological role of SGLT1 in HF.

Echocardiographic left ventricular geometry profiles for prediction of stroke, coronary heart disease and all-cause mortality in the Chinese community: a rural cohort population study

BackgroundThe utility of echocardiographic left ventricular (LV) geometry in the prediction of stroke/coronary heart disease (CHD) and all-cause mortality is not well characterized. This study aimed to evaluate the overall and sex-specific prognostic value of different geometric patterns on the incidence of stroke/CHD and all-cause mortality in a Chinese population-based cohort.MethodsWe conducted a prospective study in the general population in Northeast China, and a total of 9940 participants aged ≥ 35 years underwent echocardiography for LV geometry and were successfully followed up for incident stroke/CHD and all-cause death. Cox proportional hazards models were utilized to estimate the association of baseline LV geometry with adverse outcomes.ResultsOver a median follow-up of 4.66 years, abnormal LV geometric patterns had increased crude incident rates of stroke/CHD and all-cause mortality compared with normal geometry in overall population and each sex group (all P < 0.05). Multivariable Cox analysis reported that LV concentric and eccentric hypertrophy were associated with incident stroke/CHD (concentric hypertrophy: hazard ratio (HR) = 1.39, 95% confidence interval (CI) = 1.04–1.86; eccentric hypertrophy: HR = 1.42, 95% CI = 1.11–1.82) and all-cause mortality (concentric hypertrophy: HR = 1.50, 95% CI = 1.07–2.12; eccentric hypertrophy: HR = 1.58, 95% CI = 1.19–2.10), and LV concentric remodeling was related to stroke/CHD incidence (HR = 1.42, 95% CI = 1.09–1.84) in total population compared to normal geometry after the adjustment for potential confounders. In men, a significant increase was observed from LV eccentric hypertrophy for incident stroke/CHD, whereas in women, LV concentric hypertrophy was associated with elevated incidence of both stroke/CHD and all-cause death, and eccentric hypertrophy was correlated with increased all-cause mortality (all P < 0.05).ConclusionsOur prospective cohort supports that abnormal LV geometry by echocardiography has a prognostic significance for incident stroke/CHD and all-cause mortality, implying that early detection and intervention of LV structural remodeling in rural China are urgently needed to prevent adverse outcomes.

Influence of plasma ST2 level on myocardial remodeling in NSTEMI

Abstract Funding Acknowledgements Type of funding sources: None. Objective to establish a relationship between types of myocardial remodeling and plasma ST2 levels in NSTEMI. Methods. 90 patients with NSTEMI were examined. Features of structural and functional condition of the myocardium were determined by echocardiography in M-, B, and D-modes. All of research corresponding to the principles of the Declaration of Helsinki of the World Medical Association. Results. It is established, that relatively low level (RL) corresponded to 24, the relatively moderate level (RM) to 44, and the relatively high (RH) level of ST2 to 24 individuals, respectively. For patients in the main group, these levels were &amp;lt; 26 and &amp;gt; 56 ng / ml, respectively. Instead, the relatively moderate (or intermediate) ST2 level (RM) for these patients was 26-56 ng / ml. It was determined that in patients with explosives in comparison with RH levels of ST2 in blood plasma there is a significant increase in the value of LA (42 mm vs. 38 mm, p-0.03), iLA (20.3 mm / m2 vs. 18.3 mm / m2, p-0.04), ESS (36 mm vs. 32 mm, p-0.008), EDS (52 mm vs. 49 mm, p-0.04), Ve / Va ratio (0.79 vs. 0.74, p-0.03), iLC (2.72 vs. 2.06, p = 0.03), iMMLV (121 g / m2 vs. 108 g / m2, p = 0.04), a decrease in the ratio of RV to EDS (0.49 vs. 0.54, p = 0.01) and the value of EF (56% vs. 61%, p = 0.03) (Tab. 1). The ratio of LA to RA was 1.13 against 1.06, p= 0.04. In addition, in patients with RH level compared with patients with RM level, there was a significant increase in the value of ESS (36 mm vs. 34 mm, p = 0.05). The ratio of Ve / Va was 0.79 vs. 0.66, p =0.01, iLC -2.72 vs. 2.43, p-0.0006. Conclusion. Elevated ST2 levels greater than 56 ng / ml in patients with NSTEMI were found to be associated with more severe structural left ventricular remodeling, left atrial overload, and decreased left ventricular contractility. The latter is manifested by a decrease in the value of PV and an increase in the value of Ve / Va, which changes in the direction of the formation of a restrictive type of diastolic transmitral blood flow. In turn, the ratio of RV to EDS shows the advantage of LV dilatation over RV. Tab. 1Echo indicatorsRL level ST2RM level ST2RH level ST2PLA, mm38 (35; 39)39 (37; 41)42 (37; 42)Р1-3 = 0,03EDS, mm49 (46; 52)50 (48; 53)52 (48; 54)Р1-3 = 0,04EF, %61 (59; 64)59 (53; 62)56 (58; 60)Р1-3 = 0,03Ve/Va0,64 (0,56; 0,78)0,66 (0,58; 0,74)0,79 (0,60; 1,20)Р1-3 = 0,03 Р2-3 = 0,01іММLV, g/m2108 (91; 117)115 (100; 127)121 (106; 130)Р1-3 = 0,04

EARLY AND CONTINUOUS DETECTION OF LEFT ATRIAL PHASIC DYSFUNCTION IN THE PROGRESSION OF HYPERTENSIVE CARDIAC REMODELING

Objective: Objective: The left atrium (LA) modulates left ventricular (LV) filling and cardiovascular performance with its reservoir, conduit, and booster pump functions. We used two dimensional speckle tracking echocardiography (2DSTE)-based strain and strain rate to evaluate LA mechanics in hypertensive patients with or without LA/LV structural remodeling. Design and method: Design and Method: We enrolled 30 healthy controls (Group I) and 302 HT patients, and we divided HT patients according to LV and LA structural remodeling. Group II (n = 101), HT without LVH and LA volume index (LAVI) &lt; 28 mL/m2; Group III (n = 82), HT without LVH and LAVI &gt; 28 mL/m2; Group IV (n = 98), HT with LVH and E/e‘ &lt; 13; Group V (n = 21), HT with LVH and E/e‘ &gt; 13. The strain and strain rate images were studied, and the following parameters were measured: LA reservoir strain and strain rate (LAS-S, LASR-S), LA conduit strain and strain rate (LAS-E and LASR-E), LA booster strain and strain rate (LAS-A and LASR-A). LA stiffness index (LASI) was defined as the ratio of E/e‘ to LAS-S. Results: Results: LASI was significantly higher in Group II than Group I (p &lt; 0.05), and further increased in Group III and IV. LASI is the highest in Group V (p &lt; 0.001 vs Group I and II, p &lt; 0.05 vs Group III and IV). Generally, All strain and strain rate parameters, including LAS-S, LASR-S, LAS-E, LASR-E, LAS-A and LASR-A, gradually and significantly decreased from Group I to Group V. We also explored the correlation between LASI and cardiovascular risk factors as well as the other markers of TOD in HT. LASI was correlated with age, diabetes, hemoglobin A1c, systolic blood pressure, BMI, LVMI, Ma/Cre, carotid IMT, PWV, Triglycerides and eGFR. Multivariate regression analysis revealed that age, BMI, PWV and Ma/Cre were independent factors related to LASI. Conclusions: Conclusions: The abnormality of LA mechanics precedes LA enlargement and LVH in HT, and strain-derived LA phasic function declined further along with LA and LV remodeling and diastolic dysfunction. LASI can be identified as a detective biomarker of left cardiac remodeling and diastolic dysfunction in HT.

Left ventricular reverse remodeling and function by strain analysis in aortic stenosis: A CMR analysis of the EPICHEART study

Introduction and objectivesIn severe aortic stenosis (AS), the impact of aortic valve replacement (AVR) on left ventricular (LV) systolic function assessed by strain and measured by echocardiography or cardiac magnetic resonance (CMR) has been controversial. We aimed to investigate LV systolic myocardial function changes six months after AVR using global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain derived from CMR imaging. MethodsWe included 39 severe AS patients (69.3±7.8 years; 61.5% male) with preserved LV ejection fraction (LVEF) who were recruited as part of the EPICHEART study and underwent successful AVR (aortic valvular area: 0.8 cm2 (IQR: 0.2) pre- to 1.8 cm2 (IQR:0.5) post-AVR). Structural and functional parameters were assessed at baseline and six months after AVR, including LV GRS, GCS and GLS analysis by CMR, using cine short-axial and two-, three-, and four-chamber long-axial view. Comparison between baseline and postoperative LV remodeling was performed using Student t-test and Wilcoxon test. ResultsAt six-month follow-up, LV mass, end-diastolic and end-systolic volumes, stroke volume, cardiac output, lateral E/e’, tricuspid annular plane systolic excursion, right ventricular (RV) S wave velocity, GLS [-15.6% (IQR: 4.39) to -13.7% (IQR: 4.62)] and GCS [-17.8±3.58% to -16.1±2.94%] reduced significantly, while LVEF and GRS remained unchanged and lateral e’ velocity increased. ConclusionsDespite favorable reverse LV structural and diastolic functional remodeling six months following AVR, GLS and GCS assessed by CMR reduced compared to baseline, LVEF remained unchanged. The clinical utility and timing of assessment of postoperative strain changes as a marker of systolic function progression needs further research.

Ultrasound-targeted microbubble destruction-mediated Ang1 gene transfection improves left ventricular structural and sympathetic nerve remodeling in canines with myocardial infarction.

BackgroundThe present study aimed to determine whether ultrasound-targeted microbubble destruction (UTMD)-mediated angiopoietin 1 (Ang1) gene transfection can improve angiogenesis and potentially reverse left ventricular (LV) structural and sympathetic nerve remodeling in canines with myocardial infarction (MI).MethodsThirty dogs were randomly divided into groups (n=10/group) as follows: the MI group (MI dogs without UTMD treatment), the UTMD group (MI dogs with UTMD-mediated negative control plasmid treatment), and the UTMD-Ang1 group (MI dogs with UTMD-mediated Ang1 plasmid treatment). LV dimensions, systolic function, and synchrony were used to reflect the structural remodeling. The density of tyrosine hydroxylase (TH)- and growth-associated protein 43 (GAP43)-positive nerve fibers were calculated to assess the sympathetic nerve remodeling.ResultsOne month after treatment, the UTMD-Ang1 group showed lower LV end-diastolic dimension (LVEDD: 31.2±2.3 mm) and higher LV ejection fraction (LVEF: 44.6%±4.3%) than the MI group (LVEDD: 34.5±2.2 mm, t=2.282, P=0.014; LVEF: 37.3%±3.1%, t=3.718, P=0.003) and the UTMD group (LVEDD: 34.1±2.8 mm, t=2.264, P=0.040; LVEF: 39.3%±4.5%, t=2.408, P=0.030). LV synchrony was higher in the UTMD-Ang1 group compared with the MI group by 2-dimensional speckle-tracking echocardiography. Angiogenic density was higher in the UTMD group than the MI group but was highest in the UTMD-Ang1 group according to immunohistochemistry of CD31 and α-smooth muscle actin staining. The density of TH- and GAP43-positive nerve fibers were decreased in the UTMD-Ang1 group (TH: 1,928.2±376.6 μm2/mm2; GAP43: 2,090.8±329.2 μm2/mm2) compared with the MI group (TH: 2916.5±558.4 μm2/mm2, t=4.069, P=0.001; GAP43: 3,275.4±548.6 μm2/mm2, t=5.153, P=0.000) and the UTMD group (TH: 2,552.7±408.1 μm2/mm2, t=3.181, P=0.007; GAP43: 2,630.5±419.3 μm2/mm2, t=2.863, P=0.013). The relative Ang1 and sarcoplasmic reticulum Ca2+-ATPase 2a protein levels were significantly higher in the UTMD-Ang1 group than the UTMD and MI groups by Western blot, while the phospholamban levels exhibited the opposite trend. Plasma norepinephrine and N-terminal pro-B-type-natriuretic peptide were significantly reduced in the UTMD-Ang1 group from day 1 to 1 month after MI.ConclusionsUTMD-mediated Ang1 transfection can promote angiogenesis, reverse LV structural and sympathetic nerve remodeling, and improve LV synchrony after MI.

Abstract 15011: Association of Pulmonary Hemodynamics and Right Ventricular Function With Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Higher pulmonary artery systolic pressure (PASP) and right ventricular (RV) dysfunction are associated with higher risk of heart failure (HF) and mortality. Whether higher PASP and lower RV function are associated with risk of atrial fibrillation (AF) is unclear. Hypothesis: Higher PASP, higher pulmonary vascular resistance (PVR), and lower RV function are associated with incident AF after accounting for left atrial (LA) size and function, and left ventricular (LV) systolic and diastolic function. Methods: ARIC participants free of prevalent coronary heart disease (CHD), HF, AF, and with LA volume index (LAVi) &lt;34ml/m 2 and average E/e’ ratio &lt;14 in 2011-13 were included. We measured PASP, PVR, RV fractional area change (RVFAC), and RV-PA coupling (defined as RVFAC/PASP ratio) from 2D-echocardiograms. Incident AF (through 2018) was ascertained from hospital discharge codes and death certificates. We used Cox proportional hazards regression in our analysis. Results: We included 1915 participants (mean age 75 years, 69% female, 24% black) of whom 176 developed AF over a median follow-up of 6.3 years. PASP, PVR, and RV-PA coupling were significantly associated with incident AF after adjusting for measures of LA and LV structural and functional remodeling. RVFAC was not significantly associated with incident AF. Conclusions: In persons without CHD, HF, and LA enlargement, higher PASP and lower RV-PA coupling are associated with higher risk of AF after accounting for LA and LV structural and functional remodeling. This finding, which suggests a possible etiological role of RV remodeling for AF, needs further confirmation.