Left Ventricular Posterior Wall Thickness Research Articles

Decreased plasma ELABELA level as a novel screening indicator for heart failure: a cohort and observational study.

The predictive power of B-type natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) is limited by its low specificity in patients with heart failure (HF). Discovery of more novel biomarkers for HF better diagnosis is necessary and urgent. ELABELA, an early endogenous ligand for the G protein-coupled receptor APJ (Apelin peptide jejunum, Apelin receptor), exhibits cardioprotective actions. However, the relationship between plasma ELABELA and cardiac function in HF patients is unclear. To evaluate plasma ELABELA level and its diagnostic value in HF patients, a total of 335 patients with or without HF were recruited for our monocentric observational study. Plasma ELABELA and Apelin levels were detected by immunoassay in all patients. Spearman correlation analysis was used to analyze the correlation between plasma ELABELA or Apelin levels and study variables. The receiver operating characteristic curves were used to access the predictive power of plasma ELABELA or Apelin levels. Plasma ELABELA levels were lower, while plasma Apelin levels were higher in HF patients than in non-HF patients. Plasma ELABELA levels were gradually decreased with increasing New York Heart Association grade or decreasing LVEF. Plasma ELABELA levels were negatively correlated with BNP, left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular posterior wall thickness and positively correlated with LVEF in HF patients. In contrast, the correlation between plasma Apelin levels and these parameters is utterly opposite to ELABELA. The diagnostic value of ELABELA, Apelin, and LVEF for all HF patients was 0.835, 0.673, and 0.612; the sensitivity was 62.52, 66.20, and 32.97%; and the specificity was 95.92, 67.23, and 87.49%, respectively. All these parameters in HF patients with preserved ejection fraction were comparable to those in total HF patients. Overall, plasma ELABELA levels were significantly reduced and negatively correlated with cardiac function in HF patients. Decreased plasma ELABELA levels may function as a novel screening biomarker for HF. A combined assessment of BNP and ELABELA may be a good choice to increase the accuracy of the diagnosis of HF.

Left ventricular global longitudinal strain is worse in BRCA mutation positive breast cancer patients prior to cancer treatment and premature menopause.

Breast cancer patients with mutations in human tumor suppressor genes BRCA1 and BRCA2 are at higher risk of cardiovascular disease (CVD) than the general population, as they are frequently exposed to cardiotoxic chemotherapy, anti-estrogen therapy, radiation, and/or oophorectomy for cancer-related treatment and prophylaxis. Animal and cell culture models suggest that BRCA mutations may play an independent role in heart failure. We sought to evaluate cardiac structure and function in female BRCA1 and BRCA2 mutation carriers with breast cancer compared to BRCA wildtype women with breast cancer. We performed a 1:2 age- and hypertension-matched retrospective cohort study comparing BRCA1 and BRCA2 mutation carriers (n = 38) versus BRCA wildtype controls (n = 76) with a new diagnosis of breast cancer. Echocardiographic data were obtained within 6months of breast cancer diagnosis and prior to chemotherapy, anti-estrogen therapy, radiation, or oophorectomy. Left ventricular global longitudinal strain (LV-GLS), a highly sensitive marker of LV function, was measured using QLab 15 (Philips Healthcare). In the total cohort of 114 patients with a new diagnosis of breast cancer, the median age was 45 ± 11years and the prevalence of hypertension was 8%. There were no differences in traditional cardiovascular disease risk factors between cases and controls. BRCA carriers had lower LV-GLS (-18.1% ± 4.7% vs. -20.1% ± 3.8%, p = 0.02) and greater right atrial area (12.9cm2 ± 2.7cm2 vs. 11.8cm2 ± 2.0cm2, p = 0.04) compared to controls; however, both LV-GLS and right atrial area were within the normal range. Compared to controls, BRCA carriers had a trend toward worse LV posterior wall thickness (0.89cm ± 0.15cm vs. 0.83cm ± 0.16cm, p = 0.06) although not statistically significant. In women with newly diagnosed breast cancer and prior to treatment, LV-GLS was worse in BRCA1 and BRCA2 mutation carriers compared to those with BRCA wildtype. These findings suggest that BRCA mutations may be associated with subtle changes in cardiac function. Whether differences in GLS translate to increased cardiovascular risk in women with BRCA mutations needs to be further characterized.

Histologically Validated Myocardial Fibrosis in Relation to Left Ventricular Geometry and Its Function in Aortic Stenosis.

Background and Objectives: The combination of aortic valve stenosis (AS) and ischemic heart disease (IHD) is quite common and is associated with myocardial fibrosis (MF). The purpose of this study was to evaluate the association between the histologically verified left ventricular (LV) MF and its geometry and function in isolated AS and AS within IHD groups. Materials and Methods: In a single-center, prospective trial, 116 patients underwent aortic valve replacement (AVR) with/without concomitant surgery. The study population was divided into groups of isolated AS with/without IHD. Echocardiography was used, and LV measurements and aortic valve parameters were obtained from all patients. Myocardial tissue was procured from all study patients undergoing elective surgery. Results: There were no statistical differences between isolated AS and AS+IHD groups in LV parameters or systolic and diastolic functions during the study periods. The collagen volume fraction was significantly different between the isolated AS and AS+IHD groups and was 7.3 ± 5.6 and 8.3 ± 6.4, respectively. Correlations between MF and left ventricular end-diastolic diameter (LVEDD) (r = 0.59, p = < 0.001), left ventricular mass (LVM) (r = 0.42, p = 0.011), left ventricular ejection fraction (LVEF) (r = -0.67, p < 0.001) and an efficient orifice area (EOA) (r = 0.371, p = 0.028) were detected in isolated AS during the preoperative period; the same was observed for LVEDD (r = 0.45, p = 0.002), LVM (r = 0.36, p = 0.026), LVEF (r = -0.35, p = 0.026) and aortic annulus (r = 0.43, p = 0.018) in the early postoperative period; and LVEDD (r = 0.35, p ≤ 0.05), LVM (r = 0.43, p = 0.007) and EOA (r = 0.496, p = 0.003) in the follow-up period. In the group of AS and IHD, correlations were found only with LV posterior wall thickness (r = 0.322, p = 0.022) in the follow-up period. Conclusions: Histological MF in AS was correlated with LVM and LVEDD in all study periods. No correlations between MF and LV parameters were found in aortic stenosis in the ischemic heart disease group across all study periods.

Impact of birth weight to placental weight ratio and other perinatal risk factors on left ventricular dimensions in newborns: a prospective cohort analysis.

To investigate the association between birth weight to placental weight (BW/PW) ratio, and echocardiographic left ventricle (LV) morphology at birth, while accounting for other relevant perinatal factors. A prospective cohort study was conducted on neonates at NewYork-Presbyterian Brooklyn Methodist Hospital from 2014 to 2018, categorized by their BW/PW percentile. Missing data were imputed with principal component analysis. Chi-squared and one-way analysis of variance were used to compare BW/PW groups and the best regression model was selected using a genetic and backward stepwise algorithm. We analyzed 827 neonates in three BW/PW groups: small (n=16), normal (n=488), and large (n=323). Placental thickness and smallest diameter were positively correlated with several LV parameters, including inter-ventricular septal thickness during diastole (IVSd) (p=0.002, p<0.001) and systole (IVSs) (p=0.001, p<0.001), LV posterior wall thickness at end of diastole (LVPWd) (p=0.003, p<0.001) and systole (LVPWs) (p<0.001, p<0.001), LV mass (p=0.017, p<0.001), and LV mass/volume (p=0.011, p<0.001). The BW/PW ratio correlated with an increased shortening fraction (estimate=0.29, 95 % CI 0.03-0.55, p=0.027). PW correlated with IVSs (p=0.019), while the longest placental diameter was linked to a decrease in LV internal dimension during diastole (LVIDd) (estimate=-0.07, p=0.039), LV mass (estimate=-0.11, p=0.024), and LV mass/volume (estimate=-0.55, p=0.005). This study found that several placental factors, including the BW/PW ratio, can independently affect LV dimension and morphology, highlighting the importance of fetal growth and placental health in the physiological adaptation of the fetal heart. More research is needed to establish causation and inform newborn prevention strategies.

APOEε4 carriage associates with improved myocardial performance from adolescence to older age

BackgroundAlthough APOE ε4 allele carriage confers a risk for coronary artery disease, its persistence in humans might be explained by certain survival advantages (antagonistic pleiotropy).MethodsCombining data from ~ 37,000 persons from three older age British cohorts (1946 National Survey of Health and Development [NSHD], Southall and Brent Revised [SABRE], and UK Biobank) and one younger age cohort (Avon Longitudinal Study of Parents and Children [ALSPAC]), we explored whether APOE ε4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional metrics by echocardiography and cardiovascular magnetic resonance (CMR).ResultsCompared to the non-APOE ε4 group, APOE ε4 carriers had similar cardiac phenotypes in terms of LV ejection fraction, E/e’, posterior wall and interventricular septal thickness, and LV mass. However, they had improved myocardial performance resulting in greater LV stroke volume generation per 1 mL of myocardium (higher myocardial contraction fraction). In NSHD (n = 1467) and SABRE (n = 1187), ε4 carriers had a 4% higher MCF (95% CI 1–7%, p = 0.016) using echocardiography. Using CMR data, in UK Biobank (n = 32,972), ε4 carriers had a 1% higher MCF 95% (CI 0–1%, p = 0.020) with a dose-response relationship based on the number of ε4 alleles. In addition, UK Biobank ε4 carriers also had more favorable radial and longitudinal strain rates compared to non APOE ε4 carriers. In ALSPAC (n = 1397), APOE ε4 carriers aged < 24 years had a 2% higher MCF (95% CI 0–5%, p = 0.059).ConclusionsBy triangulating results in four independent cohorts, across imaging modalities (echocardiography and CMR), and in ~ 37,000 individuals, our results point towards an association between ε4 carriage and improved cardiac performance in terms of LV MCF. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed to the pleiotropic effects APOE ε4 carriage that might collectively explain its persistence in human populations.

Insulin resistance, C-reactive protein, diastolic to systolic blood pressure ratio and epicardial fat are related to sedentary time, and inversely related to physical activity in school-aged children.

Physical activity (PA) is beneficial for the overall health. Objectives are: (1) To compare metabolic (MRM) and cardiovascular-risk-markers (CRM) in children according to their PA-level; (2) to explore the associations of MRM and CRM with PA and sedentary time (ST); and (3) to identify the associations between MRM and CRM in less (LA) and more active (MA) children. A total of 238 apparently healthy school-aged children were enrolled (132 boys/106 girls; 9.1 ± 1.8 years) and body mass index standard deviation score (BMI SDS) and blood pressure were assessed. Fasting venous blood sampling was performed to assess insulin resistance (HOMA-IR) and high-sensitivity-C-reactive protein (hsCRP). Epicardial fat, interventricular septal and left ventricular posterior wall thicknesses were assessed by high-resolution ultrasonography. PA and ST were assessed by enKid-questionnaire. Children were classified based on enKid-score as being LA and MA (below and above 50th percentile for PA). MA-children had lower values for: BMI SDS, diastolic-to-systolic blood pressure ratio, HOMA-IR and hsCRP (7.02 to 61.5% lower, p = 0.040 to p < 0.0001) compared to LA-children. MRM and CRM were positively associated with ST (p = 0.003 to p < 0.001), and negatively associated with PA (p = 0.044 to p < 0.001). Finally, MRM were positively associated with CRM (p = 0.008 to p < 0.0001). Interestingly, the latter associations were observed in LA-children but were not present in MA-children. More PA is associated with better cardio-metabolic profile in school-aged children. PA seems to modulate the associations between MRM and CRM, thus reinforcing the idea that fostering PA in children may lower the risk for development of a cardio-metabolic disease.

Abstract P437: Cumulative Effect of Early-Onset Type 2 Diabetes on Left Ventricular Geometry - The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Type 2 diabetes (T2D) is increasingly common in young adults. Increases in left ventricular (LV) mass and wall thickness are early manifestations of myocardial involvement in T2D. The association between the cumulative burden of risk factors (RFs) and LV structural abnormalities in patients with early-onset T2D has not been well characterized. Objective: Investigate how metabolic RFs accumulated in a 25-year period among patients with early-onset T2D relate to LV mass index (LVMI) and relative wall thickness (RWT). Methods: We used data from the Coronary Artery Risk Development in Young Adults study (CARDIA, baseline to year 25). We defined early-onset T2D by self-reported T2D or anti-diabetic medication use, fasting glucose (FG) ≥126 mg/dL, or oral glucose ≥200 mg/dL at or before follow-up year 10 (age&lt;40). LV outcomes were measured by Doppler echocardiography (LVMI by Devereux formula indexed to body surface area; RWT = LV posterior wall thickness at end diastole x 2/LV internal dimension at end-diastole). Hypertrophy was defined by LVMI ≥115 g/m 2 in men or ≥95 g/m 2 in women. We used the area under the growth curve (AUC) that was derived from quadratic random-effects models of ≥4 repeated measures of RFs (BMI, SBP, DBP, LDL-c, HDL-c, triglycerides, fasting glucose, and fasting insulin) to estimate the cumulative burden of T2D through adulthood. We performed linear regressions to examine the associations of the total AUC of each RF with LVMI or RWT, accounting for sex, race, mid-life age, education, smoking, and control for hypertension, lipids, and diabetes. We assessed the associations by sex and race. Results: Among 227 patients with early-onset T2D, 39% had hypertrophy, and 13% had RWT&gt;0.42 at midlife. Each standard deviation (SD) increase in total AUCs of BMI, SBP, DBP, triglycerides, FG, and fasting insulin was significantly associated with increased LVMI (β coefficients =5.9, 11.5, 10, 7, 4.1, and 6.7, respectively), while high total AUC of HDL-c was inversely associated with LVMI (β = -5.1). Increased total AUC of triglycerides was associated with increased RWT (β = 0.2). Significant sex and race differences were shown in the cumulative effect of RFs on outcomes. The positive associations between AUC of RFs and LVMI were significant in both sexes, but the associations were stronger in male patients than in women. The inverse association between AUC of HDL-c and LVMI was only significant in male patients (P-interaction &lt;0.05). Women with early-onset T2D but not men exhibited significantly increased RWT related to the increase in AUCs of SBP, DBP, triglycerides, FG, and insulin (P-interaction &lt;0.05). The positive association between AUC of BMI and LVMI was significant in Whites but not Blacks (P-interaction &lt;0.05). Conclusion: Cumulative RFs alter mid-adulthood LV geometry in patients with early-onset T2D. This cumulative impact of early-onset T2D on LV geometry varies by sex and race.

Association of echocardiography-related parameters with the prognosis of decompensated cirrhosis: a retrospective cohort study

Background Cardiac morphology and function, which are conventionally evaluated by echocardiography, are often abnormal in decompensated cirrhosis. We aimed to evaluate the association of echocardiography-related parameters with prognosis in cirrhosis. Methods This retrospective study included 104 decompensated cirrhotic patients, in whom cardiac structure and function were measured by echocardiography, including mitral inflow early diastolic velocity/mitral inflow late diastolic velocity (E/A), left atrium diameter, left ventricular end-diastolic dimension, interventricular septal thickness, left ventricular posterior wall thickness, right atrial transverse diameter, right atrial longitudinal diameter, right ventricular dimension (RVD), stroke volume, cardiac output, left ventricular ejection fraction, and fractional shortening. Cox regression and competing risk analyses and Kaplan-Meier and Nelson-Aalen cumulative risk curves were used to evaluate their associations with further decompensation and death in cirrhotic patients, if appropriate. Results Lower RVD was a predictor of further decompensation in Cox regression (adjusted by Child-Pugh score: p = 0.138; adjusted by MELD score: p = 0.034) and competing risk analyses (p = 0.003), and RVD ≤17 mm was significantly associated with higher cumulative incidence of further decompensation in Kaplan-Meier (p = 0.002) and Nelson-Aalen cumulative risk curves (p = 0.002). E/A ≤ 0.8 was a significant predictor of death in Cox regression (adjusted by Child-Pugh score: p = 0.041; adjusted by MELD score: p = 0.045) and competing risk analyses (p = 0.024), and E/A ≤ 0.8 was significantly associated with higher cumulative incidence of death in Kaplan-Meier (p = 0.023) and Nelson-Aalen cumulative risk curves (p = 0.024). Other echocardiography-related parameters were not significantly associated with further decompensation or death. Conclusion RVD and E/A may be considered for the prognostic assessment of decompensated cirrhosis.

Biomarkers and subclinical left ventricular dysfunction in patients with type 2 diabetes without clinical manifestations of cardiovascular diseases

Aim. To study the relationship between the structural and functional left ventricular (LV) parameters and N-terminal pro-brain natriuretic peptide (NT-proBNP) and inflammatory markers in patients with type 2 diabetes (T2D) without clinical manifestations of cardiovascular diseases, as well as to evaluate the possibility of their use for early diagnosis of subclinical LV dysfunction.Material and methods. Data from 120 patients of both sexes aged 45-75 years (57,11±7,9 years) were analyzed. They were divided into three following groups: 1st — with T2D (n=47), 2nd — with prediabetes (n=20), 3rd — control (n=53). All participants underwent transthoracic echocardiography with assessment of the linear and volumetric heart dimensions, systolic and diastolic LV function. Speckle tracking echocardiography was analyzed with calculation of LV global longitudinal strain (GLS). The blood levels of NT-proBNP and inflammatory markers were determined (high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6).Results. According to echocardiography, patients with carbohydrate metabolism disorders revealed significantly higher LV mass values, LV posterior wall thickness, and relative wall thickness in comparison with the control group. Transmitral flow parameters, as well as tissue Doppler sonography, in the T2D and prediabetes groups were significantly different from those in the control group. GLS in the groups of patients with carbohydrate metabolism disorders was lower than in the control group (p=0,001). The level of NT-proBNP was significantly higher in the T2D and prediabetes groups compared to the control group, while in all three groups it did not exceed normal values (p&lt;0,001). A higher level of NT-proBNP was associated with hypertension — odds ratio (OR) 3,64 [1,02-13,04] (p=0,005), a decrease in LV ejection fraction — OR 1,25 [1,06-1 ,47] (p=0,007), concentric hypertrophy — OR 4,84 [1,43-16,41] (p=0,011) and decreased GLS — OR 1,85 [1,62-2,06] (p=0,005), an increase in the ratio of early and late diastolic transmitral flow (E/A) — OR 0,01 [0,008-0,416] (p=0,024) and isovolumic relaxation time (IVRT) — OR 1,08 [1,03-1,14] (p=0,03). The sensitivity and specificity of NT-proBNP as a test for predicting GLS reduction &lt;-18% were 86 and 27%, respectively. The hsCRP level, within the reference values, was significantly higher in the T2D and prediabetes groups compared to the control group (p&lt;0,001) and demonstrated a direct linear relationship with E/A, IVRT, early diastolic deceleration time (p&lt;0,05). A higher level of hsCRP was significantly associated with diastolic dysfunction — OR 1,16 [1,02-1,32] (p=0,023), as well as with a GLS decrease &lt;-18% — OR 1,58 [1,12-4,65] (p=0,03).Conclusion. In patients with T2D without clinical manifestations of cardiovascular disease, the presence of concentric LV myocardial hypertrophy, LV diastolic dysfunction and decreased GLS (&lt;-18%) is associated with higher blood levels of NT-proBNP and hsCRP. However, in all cases, the levels of biomarkers do not exceed the reference values, which does not allow their use in the early diagnosis of subclinical LV dysfunction in T2D.

Percutaneous intramyocardial septal radiofrequency ablation after 5-year follow-up

ObjectiveThe objective is to evaluate the 5-year follow-up results of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for hypertrophic obstructive cardiomyopathy (HOCM), including clinical status, electrocardiographic and echocardiographic characteristics.Methods27 patients (age:...

Anserine, a Histidine-Containing Dipeptide, Suppresses Pressure Overload-Induced Systolic Dysfunction by Inhibiting Histone Acetyltransferase Activity of p300 in Mice.

Anserine, an imidazole dipeptide, is present in the muscles of birds and fish and has various bioactivities, such as anti-inflammatory and anti-fatigue effects. However, the effect of anserine on the development of heart failure remains unknown. We cultured primary cardiomyocytes with 0.03 mM to 10 mM anserine and stimulated them with phenylephrine for 48 h. Anserine significantly suppressed the phenylephrine-induced increases in cardiomyocyte hypertrophy, ANF and BNP mRNA levels, and histone H3K9 acetylation. An in vitro histone acetyltransferase (HAT) assay showed that anserine directly suppressed p300-HAT activity with an IC50 of 1.87 mM. Subsequently, 8-week-old male C57BL/6J mice were subjected to transverse aortic constriction (TAC) and were randomly assigned to receive daily oral treatment with anserine-containing material, Marine Active® (60 or 200 mg/kg anserine) or vehicle for 8 weeks. Echocardiography revealed that anserine 200 mg/kg significantly prevented the TAC-induced increase in left ventricular posterior wall thickness and the decrease in left ventricular fractional shortening. Moreover, anserine significantly suppressed the TAC-induced acetylation of histone H3K9. These results indicate that anserine suppresses TAC-induced systolic dysfunction, at least in part, by inhibiting p300-HAT activity. Anserine may be used as a pharmacological agent for human heart failure therapy.

The evaluation of bariatric surgery effect on cardiac structure and function using transthoracic echocardiography: a cohort study

BackgroundObesity is a pathology and a leading cause of death worldwide. Obesity can harm multiple organs, including the heart. In this study, we aim to investigate the effect of bariatric surgery and following weight loss on cardiac structure and functions using echocardiography parameters in patients with morbid obesity.MethodsIn this cohort study, 30 patients older than 18 with BMI > 40 or BMI > 35 and comorbidity between March 2020 to March 2021 were studied. The patients underwent transthoracic echocardiography before and after six months of the bariatric surgery.ResultsIn total, 30 patients (28 women, 93.3%) with a mean age of 38.70 ± 9.19 were studied. Nine (30%) were diabetic, and 9 (30%) had hypertension. After six months of bariatric surgery, all physical measurements, including weight, Body mass index, and Body surface area, decreased significantly (p < 0.001). After bariatric surgery, all parameters regarding left ventricular morphology, including left ventricular mass, interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-systolic diameter, and left ventricular end-diastolic diameter, improved significantly (p < 0.001). Also, LVEF rose post-bariatric surgery (p < 0.001). TAPSE parameter indicating right ventricular function also improved (p < 0.001). Right ventricular diameter, left atrium volume, and mitral inflow E/e’ decreased significantly (p < 0.001).ConclusionSystolic and diastolic parameters refine significantly after bariatric surgery in patients with obesity. Bariatric surgery lead to significant cardiac structure and function improvement.

Optimizing cardiac amyloidosis assessment: utility of 1-h and 3-h 99mTc-PYP imaging

BackgroundTransthyretin amyloid cardiomyopathy (ATTR-CM), characterized by the extracellular deposition of an insoluble amyloid protein in the heart, is one of the main causes of heart failure in elderly patients. In this study, our primary objective was to explore the diverse applications and temporal significance of 1-h and 3-h imaging using 99mTc-PYP in the context of ATTR-CM. Additionally, we compared tracer kinetics in the heart and bone to comprehensively assess the diagnostic advantages and time-related considerations associated with these two incubation periods.MethodsTwenty-seven patients at Nagasaki University Hospital who underwent 99mTc-PYP planar, and SPECT cardiac imaging were classified into two groups (ATTR-CM-positive and -negative groups) based on the American Heart Association statement. Cardiac retention was assessed with both a semiquantitative visual score and a quantitative analysis. To assess bone accumulation, a ROI with an equal volume was drawn on the sternum and calculated as the bone-to-contralateral ratio (B/CL). We also evaluated correlation between heart-to-contralateral lung (H/CL) ratio and left ventricular wall thickness.ResultsAmong patients who underwent 99mTc-PYP imaging, the H/CL ratio was significantly higher at 1 h than at 3 h regardless of the group (from 2.20 ± 0.36 to 1.99 ± 0.35, p < 0.01 in the positive group and from 1.35 ± 0.12 to 1.19 ± 0.21, p = 0.01 in the negative group). The gap of H/CL between highest H/CL of negative case and lowest H/CL of positive case was narrower in 3 h. On the other hand, correlation between H/CL and left ventricular posterior wall thickness tends to be clearer in 3 h (p = 0.12, r = 0.30 for 1 h, p = 0.04, r = 0.39 at 3 h).ConclusionOur study suggests that both 1-h and 3-h incubation times for 99mTc-PYP imaging have different benefits for ATTR cardiac amyloidosis. A one-hour incubation may be preferable for differential diagnostic purposes, while a three-hour incubation may provide greater utility in evaluating disease severity.

Impact of Atrial Fibrillation on Heart Failure with Preserved Ejection Fraction: An Observational Cross-sectional Study from Western India

Abstract Background: Both atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist with overlapping symptoms, risk factors, and shared pathophysiology. Both conditions independently impact left atrial volume index (LAVI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, making it difficult to diagnose HFpEF in AF. Aim: The aim is to study the association of AF with NT-proBNP levels, LAVI, and left atrial (LA) size in HFpEF. Materials and Methods: An observational study of 40 patients was conducted at a Tertiary Care Center in Western India. Patients above 18 years of age with classical heart failure presentation were included and their clinical history and general and systemic examination were done along with NT-proBNP measurement and two-dimensional echocardiography for assessing heart structure and function. Results: Twenty-one patients had sinus rhythm; 19 had AF. AF patients had higher NT-proBNP levels (2599 pg/mL) compared to patients with sinus rhythm (785 pg/mL). AF patients had a greater degree of left ventricular (LV) dysfunction (higher LV end-diastolic dimensions, LV posterior wall thickness, LV mass index, LA diameter, LA volume and LAVI), more prevalence of pulmonary artery hypertension (n = 19 vs. n = 17), higher degrees of diastolic dysfunction (e.g. higher e’ septum, e’ lateral and E/e’), and higher right ventricle systolic pressure as compared to patients with sinus rhythm. Conclusions: The present study shows that AF occurs in around half of HFpEF patients, with a higher incidence in women and younger people. Patients with AF have higher rates of right heart failure, severe atrial and ventricular remodeling, and higher levels of NT-proBNP, which indicate an advanced form of the disease.

Meteorin-like plasma levels as a novel biomarker for heart failure

Abstract Introduction Meteorin-like (metrnl), a new adipokine with insulin-sensitizing and anti-inflammatory action, has recently drawn much attention due to its protective effects in the cardiovascular system. Metrnl promotes heart repair after insults like ischemia/reperfusion, cardiotoxicity, or diabetic cardiomyopathy in mice, and its circulating levels in patients have been associated with the presence and severity of coronary artery disease and heart failure, although in the latter with contradictory results. Purpose Our aim was to study the correlation between plasma metrnl levels and biochemical and echocardiographic parameters in patients hospitalized with de novo heart failure (HF) to determine whether this adipokine could be a useful biomarker/therapeutic target for HF. Methods Blood samples of 400 patients hospitalized with de novo HF were collected in a multicenter clinical study. Plasma levels of metrnl were measured by enzyme-linked immunosorbent assay. Results In de novo HF patients, metrnl plasma levels were positively correlated with age (r = 0.322, P &amp;lt; 0.0001), NT-proBNP (r = 0.293, P &amp;lt; 0.0001), troponin (r = 0.192, P &amp;lt; 0.001), creatinine (r = 0.353, P &amp;lt; 0.0001) and urea (r = 0.322, P &amp;lt; 0.0001), while negatively correlated with albumin (r = -0.308, P &amp;lt; 0.0001) and alanine aminotransferase (r = -0.183, P &amp;lt; 0.0001). Metrnl plasma levels were also positively correlated with echocardiographic data of cardiac morphology as intraventricular septum thickness (r = 0.197, P &amp;lt; 0.0001) and left ventricular posterior wall thickness (r = 0.150, P &amp;lt; 0.004). On the other hand, Cox regression analysis suggested that higher plasma metrnl was associated with increased cardiovascular mortality (HR, 1.004, P &amp;lt; 0.004)) and rate of readmission for HF (HR, 1.002, P &amp;lt; 0.008). Regarding the different types of HF, we found that metrnl plasma levels were lower in HF with reduced ejection fraction (HFrEF) in comparison those with preserved ejection fraction (HFpEF) [408.06 (354.05 - 537.71) pg/mL vs. 486.06 (391.94 – 607.80), median (interquartile range), respectively; P &amp;lt; 0.0001]. Conclusion Metrnl plasma levels were associated with markers of cardiac (troponin), renal (creatinine and urea) and hepatic (alanine aminotransferase and albumin) damage. The HF marker NT-proBNP and the echocardiographic parameters intraventricular septum thickness and left ventricular posterior wall thickness are also linked to metrnl plasma levels. Moreover, metrnl levels were found to be independent predictors of cardiovascular mortality and readmission for heart failure. And finally, metrnl plasma levels in patients hospitalized with de novo HF were increased in patients with HFpEF vs. HFrEF. Our results reinforce the relevance of the adipokine metrnl in the pathophysiology and diagnosis of HF, and supports its possible use in the future as biomarker/therapeutic target for HF.

A preliminary study on the standard value of left ventricular mechanic dyssynchrony by speckle tracking

Abstract Background Speckle tracking imaging automatic functional imaging (AFI) is a new method to measure left ventricular mechanical dyssynchrony. Parameter peak strain dispersion (PSD) is the standard deviation when the long axial strain of 17 segments of the left ventricle (LV) reach there’s peak. There is no unified standard value at present. Li C[1] included 59 healthy women aged 43.08 ± 8.22 years old, whose PSD was 31.44±3.83ms. Ji X[2] included 57 healthy volunteers aged 43.30 ±6.03 years old whose PSD value was 23.8±2.2ms. Some studies referred to the standard range of Yu index and used PSD&amp;gt;32.6ms as an indicator of left ventricular mechanic dyssynchrony. Purpose To investigate the standard value range of PSD and PSD/R-R interval. Methods Healthy volunteers who came to our hospital for physical examination from March 2020 to September 2021 were included, excluding hypertension, diabetes, hyperlipidemia, coronary heart disease and other diseases. According to the 20∼29 years old, 30∼39 years old, 40∼49 years old, 50∼59 years old, 60∼69 years old and 70∼79 years old, 10 males and 10 females were included, respectively. GE Vivid E95 was used to collect echocardiographic images, and the following parameters were measured: ①The general parameters of the heart, such as the diameter of the atrium(LA) and the left ventricle (LV) and the thickness of the left ventricular wall .; ②the values of PSD and PSD/ R-R interval. The normal distribution parameters were represented by mean plus or minus the standard deviation. Analysis of variance and post hoc test (LSDt-test) were used to analyse measured values statistically. Results Values of general echocardiographic data such as BSA, atrial and ventricular diameter, interventricular septal thickness, left ventricular posterior wall thickness, and LV ejection fraction were consistent with the guideline of Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging published in 2015. The range of PSD values for subjects in this study was 43±9ms, and the maximum was 65ms. The range of PSD/R-R was 5±1%, and the maximum was 7%. The values of PSD and PSD/R-R were 36±5ms(27∼45ms) and 4.4±0.76%(3∼6.4%) for 20∼39 years old, 42±5ms(34.9-54ms), 5.0±0.8%(3.5-6.7%) in 40∼59 years; 51±8ms(34∼65ms), 5.8±0.9%(3.9∼7%) in age 60∼79. Conclusions The preliminary study has shown that left ventricular mechanical dyssynchrony is associated with age. The standard value range of PSD is inconsistent in different age groups, and PSD and PSD/R-R values increase with age.PSD values at different agesBar chart of PSD values at different age

Histidine triad nucleotide-binding protein 2 deficiency induce myocardial glucose utilization disorder in mice

Abstract Introduction Histidine triad nucleotide-binding protein 2 (HINT2) has been shown to be benefit to energy metabolism after myocardial infarction. However, the exact mechanism of HINT2 in myocardial metabolism remains unclear. Purpose To explore the effect of HINT2 deficiency on cardiac function and metabolic profile. Methods HINT2-/- mice was generated for experiment in vivo by CRISPR/Cas9 technique. Neonatal mouse ventricle myocytes were used for in vitro experiment. Transthoracic echocardiography and histological analyses were performed to assess ventricle structure and function. Transmission electron microscopy was used to observe ultrastructure in ventricle tissues. Conjoint analysis of proteomics and metabolomics was to screen the metabolism profile and signal pathway. Seahorse XFe 96 analysis was performed to detect oxygen consumption rates and glycolysis rate. Immunoprecipitation mass spectrometry was used to explore the HINT2-interacting protein. Co-immunoprecipitation and proximity ligation assay were used to detect the interaction between proteins. Results Comparing to HINT2+/+, HINT2 deficient mice had higher level of left ventricular posterior wall thickness, and lower left ventricular ejection fraction. The heart weight/tibia length, cross-sectional area and cardiac fibrosis area were increased in HINT2 deficient mice. In HINT2 deficient, using transmission electron microscopy, thicker cardiac muscle fibers was observed, with disorganized and disorganized mitochondria. Conjoint analysis of proteomics and metabolomics exhibited the network of differential protein and metabolite, which proved HINT2 deficiency activated the pathway of diabetic cardiomyopathy. Immunoprecipitation showed that the level of glycosylated modification in heart tissues was higher in HINT2 deficient mice. Seahorse analysis showed that the basal and max oxygen consumption rate in HINT2 deficient mice was significantly lower, and so was the mitochondria related Proton efflux. With immunoprecipitation mass spectrometry detection, we found that PDK4 may have interaction with HINT2. Both co-immunoprecipitation and proximity ligation assay proved that HINT2 and PDK4 has interaction and subcellular localization. Conclusions HINT2 plays an important role in cardiac function and glucose metabolism, which is a critical molecule in process of diabetic cardiomy.

Betaine therapy of cardiac hypertrophy through inhibition of Hydroxy-carboxylic Acid Receptor 1 signaling

Abstract Background Hydroxy-carboxylic Acid Receptor 1 (HCAR1), formerly known as G protein-coupled Receptor 81 (GPR81), is a cell membrane receptor for lactate, and essential for activation of a variety of intracellular signaling pathways. We found a correlation between the activation of lactate-HCAR1 signaling and occurrence of cardiac hypertrophy. However, the regulatory mechanism remains unclear. Purpose Our purpose is to investigate the regulatory mechanism between the activation of lactate-HCAR1 signaling and occurrence of cardiac hypertrophy. Methods Neonatal rat cardiomyocytes (NRCMs) were used for preparing cardiac hypertrophy model in vitro by phenylephrine (PE) stimulation, and C57 BL/6 mice were used for preparing pressure overloaded-induced cardiac hypertrophy model in vivo by TAC (transverse aortic constriction) surgery. Adenovirus containing shRNA-HCAR1 (ADV-shHCAR1) were constructed to knockdown HCAR1 in NRCMs. Binding interaction between HCAR1 and Betaine was predicted by AUTODOCK 4 and further validated with RNA-seq analysis. Results Lactate concentration and HCAR1 expression were both increased in the NRCMs upon PE treatment. Activation of HCAR1 by its agonist 3-Chloro-5-hydroxybenzoic acid (3Cl-HBA) specially induced hypertrophy in NRCMs. Furthermore, the hypertrophy phenotypes in NRCMs showed alleviation by transfection of ADV-shHCAR1. An AI-based molecule-docking screening analysis identified Betaine as a potential molecule to bind HCAR1. Treatment with Betaine significantly attenuated PE- or 3Cl-HBA- induced hypertrophy in NRCMs in vitro. In addition, Betaine administration of TAC mice (i.g. 50 mg/kg/day) for 4 weeks in vivo led to increase of ejection fraction (EF) and decreases of left ventricular (LV) posterior wall thickness, heart weight/tibia length ((HW/TL), cross-sectional area and cardiac fibrosis area as well. RNA-seq analysis and functional assays demonstrated that Betaine could bind to HCAR1, activated Hippo signaling pathway, and thereby blocked the HCAR1-mediated hypertrophy in cardiomyocytes. Conclusions In summary, the current study not only identified HCAR1 as a therapeutic target of cardiac hypertrophy, but also demonstrated Betaine as a therapeutic candidate molecule holding potential to benefit cardiac hypertrophy patients.

Abstract 17602: Cardiac Structure and Function and Renal Outcomes in Patients With Heart Failure With Preserved Ejection Fraction: Insights From the PARAGON-HF Trial

Introduction: Chronic kidney disease is common and associated with a worse prognosis in patients with heart failure (HF). However, the association of cardiac structure and function with renal outcomes in patients with HF with preserved ejection fraction (HFpEF) is not known. Goal: Identify cardiac structural and functional correlates of renal outcomes in HFpEF. Methods: Patients enrolled in the echocardiographic sub-study of the PARAGON-HF trial were included. The endpoint of interest was a composite renal endpoint: a ≥50% decline in estimated glomerular filtration rate (eGFR) relative to baseline, development of end-stage renal disease, or death attributable to renal causes. Multivariable Cox proportional hazards models were used to identify measures of cardiac structural and functional parameters associated with the composite renal endpoint, adjusting for baseline eGFR, systolic blood pressure, NT-proBNP, treatment arm (sacubitril-valsartan or valsartan) and diabetes. Results: In 1,097 patients (53% women, mean age 74±8 years), over a median follow-up of 2.9 years (IQR 2.6-3.4 years) there were 28 composite renal events (0.9 per 100 patient-years). After multivariable adjustment, higher left ventricular (LV) posterior wall thickness and mass index, right ventricular (RV) end-diastolic and end-systolic areas as well as impaired RV function (lower fractional area change and lower absolute RV free wall longitudinal strain), but not LV systolic function (LVEF and global longitudinal strain) were each associated with a significantly higher risk for the composite renal endpoint ( Figure ). Conclusions: In the PARAGON-HF echocardiographic sub-study, evidence of cardiac biventricular remodeling and deterioration of RV function were associated with an increased risk of renal events. These results underscore the close relationship between the heart and kidneys in patients with HF even when LVEF is preserved.

Abstract 14176: Cardiac Structure and Function in Relation to Health-Related Quality of Life in Heart Failure Patients With Preserved Ejection Fraction: Results From the PARAGON-HF Study

Background: Health-related quality of life (HRQL) is reduced in patients with heart failure with preserved ejection fraction (HFpEF). However, the extent to which HRQL outcomes are related to cardiac structure and function in patients with HFpEF is not well understood. Methods: We examined the association between baseline echocardiographic measures and longitudinal Kansas City Cardiomyopathy Questionnaire (KCCQ) measures in patients with HFpEF in the PARAGON-HF trial using longitudinal regression models adjusted for age, sex, baseline KCCQ score, randomization, and other important clinical confounders. Results: Among 1,094 patients with baseline KCCQ data at randomization and a baseline echocardiogram within 6 months of enrollment, the mean age was 74 years and 53% were women. Over 3 years, 78% completed KCCQ measures at baseline, 12, 24, and 36 months. Missing values for non-survivors (n=116) were imputed as zero to avoid survival bias. Posterior wall thickness, septal E/e’, and right ventricular (RV) end diastolic area were negatively associated with the KCCQ Overall Summary Score, and a similar pattern of associations was observed for the KCCQ Clinical Summary Score (Table). Pulmonary artery systolic pressure was additionally negatively associated with the KCCQ Total Symptom Score. Notably, left ventricular (LV) size, septal wall thickness, LV ejection fraction, LV strain, and left atrial size were not significantly associated with longitudinal changes in KCCQ. Conclusion: In patients with HFpEF, increased LV posterior wall thickness, elevated LV filling pressure, elevated pulmonary pressure, and RV enlargement - together suggestive of more advanced diastolic dysfunction - are associated with a decline in KCCQ scores and may influence future worsening of quality of life.