Left Ventricular Structure Research Articles

Left ventricular myocardial deformation in patients on maintenance haemodialysis

Background Patients with chronic kidney disease (CKD) undergoing maintenance haemodialysis (MHD) develop several abnormalities of left ventricular (LV) structure and function. Speckle-tracking echocardiography permits compressive assessment of LV myocardial deformation. Previous studies involving CKD patients have shown a significant reduction in LV global longitudinal strain (GLS) with strong prognostic implications. However, the other components of LV deformation have not been fully elucidated. Methods A total of 90 CKD patients undergoing MHD (mean age 41.3 ± 12.5 years, 80% men) were compared with 45 apparently healthy age- and gender-matched controls. Results The CKD patients had a high prevalence (77.8% patients) of LV hypertrophy. They also had a significantly elevated ratio of early diastolic mitral inflow velocity to annular velocity (12.1 ± 4.6 vs. 7.1 ± 1.5, p < .001) indicating a high prevalence of LV diastolic dysfunction. LV ejection fraction (LVEF) was the same between the two groups, but the CKD patients had significantly impaired LVGLS (−17.8 ± 3.9 vs. −20.8 ± 2.6, p < .001), global circumferential strain (−14.0 ± 3.5 vs. −16.1 ± 3.4, p = .001), LV apical rotation (6.6 ± 4.7° vs. 8.8 ± 4.0°, p = .008) and LV twist (12.8 ± 6.1° vs. 15.0 ± 6.0°, p = .037). There was no difference in the global radial strain between the two groups. Conclusions The present study shows that CKD patients on MHD have significantly impaired LV longitudinal and circumferential mechanics despite preserved LVEF. The prognostic implications of reduced LVGLS have already been demonstrated previously. Future studies are needed to assess the prognostic implications of abnormal LV circumferential mechanics as well as their reversibility following renal transplant.

Abstract 4113164: Central Arterial Stiffness in Young Adults with Perinatal HIV Exposure

Intro: Young adults with perinatally acquired HIV (YPHIV) have higher morbidity and mortality than uninfected persons. Antiretroviral therapy (ART) has extended life expectancy making adult CV disease a concern. Perinatal exposure to HIV increases inflammation which is associated with increased arterial stiffness which predicts CV disease. Aims: We compared arterial stiffness between YPHIV and young adults perinatally HIV exposed but uninfected (YPHEU), and evaluated the association of type and duration of ART regimens, HIV disease severity, and cardiac structure and function with arterial stiffness. Methods: In a substudy of the Pediatric HIV/AIDS Cohort Study, 150 participants (95 YPHIV, 55 YPHEU, mean 23.4 yrs, 60% female, 72% Black, 24% Hispanic) had echocardiography and pulse wave velocity (PWV) measured. We compared PWV between YPHIV and YPHEU, adjusting for covariates. Among YPHIV, we fit linear regression models to evaluate the association of current (within 1 year of PWV) and historical measures of HIV disease severity with PWV. We computed correlations between PWV and measures of left ventricular (LV) structure and function, overall and by HIV status. Results: Mean PWV and hemodynamic parameters did not differ between YPHIV and YPHEU (YPHIV 5.63 vs YPHEU 5.39 m/s; p=0.5). HIV control was good (82% with viral load &lt;400 copies/ml), 91% used combination ART: integrase strand inhibitors (INSTIs; median duration 4.6 years), protease inhibitors (PIs 15.1 years), or non-nucleoside reverse transcriptase inhibitors (NNRTIs 5.2 years). Most participants had normal PWV compared to healthy controls but all values above 11.8 m/sec ( Figure , level associated with CV events in adults) were only in YPHIV. Only weak correlations were observed between PWV and echocardiographic measures (&lt;0.20) in both YPHEU and YPHIV. Among YPHIV, HIV severity measures were not associated with PWV using either current or historical measures. Mean PWV was 1.68 (-0.36, 3.72) m/s higher among YPHIV with current PI use than those on INSTIs, and 1.58 (-0.94, 4.11) m/s higher than those on NNRTIs, although these differences were not significant. Conclusions: PWV was within normal ranges in most YPHIV and YPHEU although 5% YPHIV had elevated PWV. PWV may be higher with PI use due to cardiometabolic side effects. Successful HIV treatment and control of traditional CV risk factors may prevent premature vascular aging and subsequent cardiac compromise in YPHIV.

Sex differences of visceral fat with cardiac structure and function in type 2 diabetes: A cross-sectional study.

The aim of this study is to analyze the associations among fat distribution, left ventricular (LV) structure, and function in T2DM patients and further assess the sex differences among them. Two thousand and one hundred seven T2DM patients were enrolled to this study. Patients' height, weight, BMI, visceral fat area (VFA), baPWV, parameters of cardiac structure and function, and clinical biochemical indicators were measured and collected. There were significant differences between male and female T2DM patients in age, duration of diabetes, complication ratio of hypertension and dyslipidemia, smoking history, visceral fat, baPWV, and ventricular structure and function (p < 0.05). Compared with the Q1 group, female patients in the highest quartile (Q4) of VFA had a decreased LVEF and significantly increased baPWV (p < 0.05), whereas no such changes were found in males. The correlation analysis showed that LVEF in male patients was negatively correlated with hypertension history, using of CCBs, GLP-1RA, lipid-lowering medications, BMI, WC, WHR, FPG, FC-P, HbA1c, GA, HOMA-IR, Cr, and baPWV, while the LVEF in female patients was negatively correlated with VFA, VSR, VFA/BMI, VFA/H2, VFA/weight in females (p < 0.05). LVMI was positively associated with diabetes duration, age, hypertension history, WC, WHR, VFA, SFA, VFA/BMI, VFA/H2, VFA/weight, and baPWV in both males and females. Multivariable-adjusted linear regression analysis showed that VFA was independently associated with LVEF (β = - 0.096, p = 0.010), LVMI (β = 0.083, p = 0.038), and baPWV (β = 0.120, p = 0.003) in females. Values of VFA were independently associated with LVEF, LVMI, and baPWV in women, but not in men, in patients with T2DM.

Association of epicardial adipose tissue with cardiac geometry alternation and diastolic dysfunction in the early stage of diabetic cardiomyopathy

Abstract Background Diastolic dysfunction and alterations in cardiac geometry are early indicators of diabetic cardiomyopathy. However, the association between cardiac changes across the glucose continuum and the contribution of epicardial adipose tissue (EAT) to these changes has not yet been investigated. Purpose In this study, we aim to investigated the EAT on cardiac diastolic function and structural alterations along the diabetic continuum using cardiac magnetic resonance imaging (CMR). Methods We enrolled individuals who were categorized into groups based on glucose tolerance status. Left ventricular structure and diastolic function were assessed using echocardiography and CMR to determine the EAT, intramyocardial fat, and associated parameters. Multivariate logistic regression models were also used. Results In a study of 370 patients (209 normal glucose tolerance, 82 prediabetes, 79 diabetes), those with prediabetes and diabetes showed increased heart dimensions and diastolic dysfunction, including E/E' (7.9±0.51 vs. 8.5±0.64 vs. 10.0±0.93, p=0.010), left atrial volume index (28.21±14.7 vs. 33.2±12.8 vs. 37.4±8.2 mL/m2, p&amp;lt;0.001), and left ventricular peak filling rate (4.46±1.75 vs. 3.61±1.55 vs. 3.20±1.30 mL/s, p&amp;lt;0.001). EAT significantly increased in prediabetes and diabetes (26.3±1.16 vs. 31.3±1.83 vs. 33.9±1.9 gm, p=0.001), while intramyocardial fat did not differ significantly. Prediabetes altered heart geometry, but not diastolic function (OR 1.22 [1.02–1.83], p=0.012; and 1.70 [0.79–3.68], p=0.135). Diabetes significantly affected both heart structure and diastolic function (OR 1.42 [1.11–1.97], p=0.032; and 2.56 [1.03–5.40], p=0.034) after adjusting for covariates. Conclusions Elevated EAT was observed in patients with prediabetes and is associated with adverse alterations in cardiac structure and diastolic function, potentially serving as an underlying mechanism for the early onset of diabetic cardiomyopathy.

Echocardiographic findings in newborns with inadequate intrauterine growth during pregnancy

Abstract Background Infants born small for gestational age (SGA) or diagnosed with fetal growth restriction (FGR) are at increased risk of neonatal mortality as well as cardiovascular disease later in life. Previous studies based on smaller cohorts (n&amp;lt;200) of newborns with SGA and FGR (n&amp;lt;200) have demonstrated structural and morphological alterations in the heart compared to infants born appropriate for gestational age (AGA). However, to our knowledge no previous study has systematically investigated the effect of SGA and FGR on echocardiographic parameters in the infant heart. Purpose To investigate whether echocardiographic parameters differ among infants born SGA or with FGR, in comparison to infants born AGA. Methods This study is a population-based cohort study of infants (n&amp;gt;25,000) offering postnatal cardiac examination including transthoracic echocardiography (TTE) between 2016-2018. We compared left ventricular (LV) TTE parameters in infants born SGA (birthweight ≥3rd and &amp;lt;10th percentile, n=2,106) and with FGR (birthweight &amp;lt;3rd percentile, n=972) with infants born AGA (birthweight ≥10th and &amp;lt;90th percentile, n=20,468) using a multiple linear regression analysis. We have investigated LV volumes, systolic function, diastolic function, and LV structure. All analyses were adjusted for sex, gestational age at birth, weight, length, and age at cardiac examination. Results Infants born SGA had higher heart rates compared with infants born AGA. Both infants born SGA and infants with FGR had significantly smaller LV dimensions including septal and posterior wall thicknesses (IVSd and LVPWd), and LV internal diameters (LVIDd and LVIDs). Infants born SGA had smaller end-diastolic and end-systolic volumes compared with infants born AGA (Table 1). Infants born SGA or with FGR had significantly higher mitral valve early peak velocities, compared with infants born AGA, and infants born SGA showed increased mitral valve atrial peak velocities indicating altered diastolic function (Table 1). Conclusion Infants born with inadequate intrauterine growth had smaller LV dimensions compared with infants born AGA, even when adjusting for infant size and age. Infants born SGA and with FGR both exhibited altered diastolic function. Longitudinal studies of children with inadequate intrauterine growth are needed to determine the impact on adult cardiac health.

Cardiac remodeling in rheumatoid arthritis: assessing the influence of anti-CCP and rheumatoid factor

Abstract Background Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF), markers of Rheumatoid Arthritis (RA) activity, are associated with adverse cardiovascular outcomes, suggesting a potential link between RA and cardiac remodeling. Purpose Our study aimed to explore the correlation between antibody levels (anti-CCP and RF) and left ventricular (LV) remodeling in RA patients without known heart disease. Additionally, it sought to identify other disease-related factors that correlate with LV remodeling. Methods A cross-sectional study of 124 RA patients aged ≥ 18 years, classified per the 2010 ACR/EULAR criteria, collected blood samples for CRP, and antibody levels (RF ≥ 20 IU/ml and anti-CCP ≥ 5 IU/ml via ELISA). Transthoracic echocardiography (TTE) was conducted using a linear method in a long-axis parasternal 2D window. Sixty-two patients exhibited LV remodeling and were matched with 62 patients without it. Echocardiographic variables included were those to calculate the relative wall thickness (RWT, cut-off value 0.42) and left ventricular mass index (LVMI, cut-off values of 43-95 g/m2 in women and 49-115 g/m2 in men) along with left ventricular end diastolic (LVIDd), and systolic volumes (LVIDs), and left ventricular ejection fraction (LVEF). Statistical analyses employed the Chi-square test, Student's t-test, or Mann-Whitney U test as applicable, with correlations assessed using Spearman's rho, an analysis was conducted on the area under the curve (AUC) and a significance level of p ≤ 0.05. Results The most common type of LV alteration in our study was concentric remodeling (74.2%). A statistically significant difference was observed in the levels of Anti-CCP titers 193.85 IU/ml (p &amp;lt; .001), RF IgM 200.00 IU/ml (p &amp;lt; .001) and IgA 185.5 IU/ml (p &amp;lt; .001) in patients with LV remodeling. Anti-CCP and RF IgA antibody levels exhibited a moderate correlation with the presence of LV remodeling, with rho 0.387 (p &amp;lt; .001) and rho 0.344 (p &amp;lt; .001), respectively. The RWT showed a moderate correlation with anti-CCP titers with rho 0.298 (p .001). AUC analysis anti-CCP titers demonstrated better diagnostic performance for the existence of cardiac remodeling (0.722, 95% CI 0.628-0.816, p &amp;lt; .001), RF IgA (0.696, 95% CI 0.602-790, p &amp;lt; .001) and IgM (0.650, 95% CI 0.563-755, p .002). Conclusion In summary, among RA patients without heart failure (HF), LV remodeling and elevated RWT correlate with antibody levels independently of traditional cardiovascular risk factors. Patients with altered LV geometry exhibit higher antibody titers, highlighting the need for RA-related biomarkers that correlate with changes in LV structure and function Recognizing association between autoimmunity and HF development holds significant implications for both prevention and treatment strategies in RA patients.

Dynamic changes of excessive trabeculation in dilated cardiomyopathy: a longitudinal cardiovascular magnetic resonance study

Abstract Background A portion of dilated cardiomyopathy (DCM) patients present with left ventricular (LV) excessive trabeculation at diagnosis. It remains unknown if the extent of trabeculation would be reduced after guideline-directed medical therapy (GDMT). Purpose To investigate the dynamic change of excessive trabeculation after GDMT in patients with DCM, and its relationship with that in LV structure and function. Methods A group of DCM patients with baseline and follow-up cardiovascular magnetic resonance (CMR) examination after 1-2 years of GDMT were enrolled. Trabeculation was assessed by Petersen method as measuring the thickness of the most prominent non-compacted (NC) layer and the corresponding compacted (C) segment at the apical long-axis view at end-diastole. Excessive trabeculation was defined as the NC/C ratio &amp;gt; 2.3, and a regression was reached if it decreased to ≤ 2.3. Major adverse cardiovascular events (MACE) consisted of cardiovascular death, heart transplantation, and heart failure readmission. Results Among 218 DCM patients (45 ± 14 years, 67.4% male), 58 (26.6%) met the excessive trabeculation criteria at baseline. Despite a similar LV ejection fraction (LVEF), patients with excessive trabeculation had a higher LV end-diastolic dimension (73.3 ± 9.0 vs. 70.5 ± 8.0mm) and native T1 (1325.3 ± 71.2 vs. 1305.5 ± 65.9mm) (both p&amp;lt;0.05) with a trend of more late gadolinium enhancement (51.7% vs. 39.4% of patients). After 15 months of GDMT, patients with excessive trabeculation (n=58) showed a decreased NC layer (12.7 ± 3.4 vs. 11.3 ± 3.0 mm) and NC/C ratio (3.1 ± 0.9 vs. 2.7 ± 0.9) (both p &amp;lt; 0.05), 25.9% of whom showed a regression of trabeculation. Patients with the regression had a lower NC/C ratio (1.8 ± 0.4 vs. 3.0 ± 0.8, p &amp;lt; 0.001) and LV end-diastolic volume index (LVEDVi) (121.5 ± 40.5 ml/m2 vs. 165.9 ± 67.8ml/m2, p=0.004) compared with those without. The change of (△) NC/C ratio was associated with that of LVEDVi (r = 0.323), and LVEF as well (r = -0.254) (both p &amp;lt; 0.001). Excessive trabeculation at baseline did not differentiate patients with a higher risk of MACE by Kaplan-Meier survival curve (p= 0.208), but its persistent presence at follow-up did (p= 0.004). However, when put △NC/C ratio, △LVEDVi, △LVEF and In NT-proBNP into multivariate cox regression model, only the △LVEDVi (HR, 0.963; 95% CI: 0.942, 0.985; P = 0.001) and In NT-proBNP (HR, 2.016; 95% CI: 1.288, 3.157; P = 0.002) were independent predictors of MACE. Conclusions Regression of excessive trabeculation occurred after GDMT in DCM patients that was related somewhat to LV reverse remodeling and not an independent predictor of MACE. It may also indicate the interconnection between LV remodeling and trabeculation.

CD14 blockade preserves left ventricular structure and systolic function in a murine model of ST-elevation myocardial infarction

Abstract Background Cluster of differentiation-14 (CD14) facilitates the excessive pro-inflammatory monocyte-macrophage response to myocardial injury. Both acute and chronic infiltration of pro-inflammatory macrophages are implicated in the immunological progression of ischemic heart failure. However, investigation of clinically practicable strategies of CD14 blockade are yet to be reported. Purpose This fully blinded and randomised preclinical study evaluated the efficacy of a neutralising anti-CD14 antibody given at reperfusion in a murine model of reperfused ST-elevation myocardial infarction (STEMI) with key clinical features. Methods Large anterior STEMI was induced in 48 adult mice by left anterior descending coronary artery occlusion for 1 h prior to reperfusion and randomisation to receive anti-CD14 antibody, isotype control (IgG2a) or saline weekly for four weeks (independently blinded). Outcome measures included functional assessments by 9.4T cardiac magnetic resonance (CMR) imaging and ultra-high-resolution echocardiography at 21- and 28-days post-STEMI, respectively. Results Multi-plane short axis CMR at 21-days post-STEMI revealed greater left ventricular (LV) ejection fraction in the anti-CD14 antibody-treated group compared with saline- and isotype-treated controls (30±1 vs 19±1 and 20±1 %, respectively, p&amp;lt;0.001; Figure 1A). CMR also revealed reduced LV dilatation with anti-CD14-treatment compared to control groups (76±5 vs 102±8 and 107±7 µl EDV in saline- and isotype-treated controls, respectively, p&amp;lt;0.05). Parasternal long axis echocardiography at 28 days post-STEMI confirmed that anti-CD14 antibody treatment was associated with greater LV systolic function compared to saline and isotype controls (30±1 vs 24±1 and 25±2 % EF, respectively, p&amp;lt;0.05; Figure 1B). Preservation of LV end-diastolic (86±4 vs 111±6 and 101±5 µl, p&amp;lt;0.01) and end-systolic (61±3 vs 84±5 and 77±5 µl, p&amp;lt;0.01) volumes was also observed with anti-CD14 treatment. Global longitudinal strain (GLS) of the LV was also significantly greater at 28 days post-STEMI with anti-CD14 treatment relative to saline and isotype controls (-8.5±0.4 vs -6.8±0.3 and -6.6±0.4 %, respectively, p&amp;lt;0.05). Conclusion(s) The findings of this fully blinded and randomised preclinical study provide evidence of a clinically practicable strategy of CD14 blockade initiated at reperfusion to mitigate progressive LV systolic dysfunction and dilatation post-STEMI.Figure 1.Functional outcome measures

Lipoprotein(a) levels and LPA genotypes are not associated with echocardiographic measures of left ventricular structure and function in the general population

Abstract Background Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for myocardial infarction and aortic valve stenosis, and elevated Lp(a) levels are associated with increased risk of heart failure. While part of this heart failure risk is mediated through atherosclerotic and valvular disease, other pathological pathways may also contribute to the association between Lp(a) and heart failure. Purpose To assess if Lp(a) levels and corresponding LPA genotypes are associated with echocardiographic measures of left ventricular structure and function in the general population. Methods We included 3,427 participants from an observational general population study who underwent protocol echocardiography between 2011-15 and had an available measurement of Lp(a) and LPA genotypes. Lp(a) was measured in 1991-94 and 2001-03 using well-validated assays with the most recent measurement used for the present analysis. Participants were divided into groups based on quartiles of Lp(a) with the top quartile further stratified to capture those above the 90th percentile. For genetic analysis, participants were grouped based on kringle IV type 2 [KIV-2] repeat corresponding to plasma Lp(a) percentile groups. Linear regression models were used to estimate β-coefficients for echocardiographic measures associated with Lp(a) levels and genotypes, while logistic regression models were used to estimate odds ratios for cardiac dysfunction or remodeling. All models were adjusted for age and sex. Results Mean age was 63±14 years and 44% were male. Median plasma Lp(a) was 18 mg/dL [IQR 10-40], median number of KIV-2 repeats were 36 [30-40], 102 (3%) were rs3798220 minor allele carriers and 467 (14%) were rs10455872 carriers. Mean left ventricular ejection fraction [LVEF] was 56.0±6.6% and we had 99% power to detect an absolute LVEF difference of 2% between those with Lp(a) levels above the 90th percentile (corresponding to &amp;gt;75 mg/dL) compared with those below the 25th percentile (&amp;lt;10 mg/dL). Mean absolute global longitudinal strain (GLS) was 19.2±2.7% and we had 99% power to detect an absolute difference of 1%. However, we found no statistically significant differences in echocardiographic measures according to Lp(a) levels or LPA genotypes (Table 1). The prevalence of impaired LVEF was 16%, and we had &amp;lt;20% power to detect an odds ratio of 1.2 for those with Lp(a) above the 90th percentile compared with those below the 25th percentile. We found no significant associations between odds for cardiac dysfunction or left ventricular hypertrophy and Lp(a) levels or LPA genotypes (Table 2). Conclusion Elevated Lp(a) levels and corresponding LPA genotypes were not associated with echocardiographic measures of left ventricular structure and function in this general population cohort. While we did not have sufficient power to detect associations between Lp(a) and cardiac dysfunction, our findings do not support a substantial effect of Lp(a).

Maternal Diabetes and Cardiac Left Ventricular Structure and Function in the Infant: A Copenhagen Baby Heart Study.

Prenatal exposure to maternal diabetes is associated with an increased risk of offspring heart defects. We evaluated associations with subtle infant cardiac changes. In a cohort of 25,486 infants with transthoracic echocardiography within 60 days of birth, we investigated associations between maternal preexisting diabetes and gestational diabetes mellitus (GDM) and infant left ventricular (LV) structural and functional parameters, using linear regression to estimate adjusted mean differences (aMDs) between groups. Infants exposed to maternal preexisting diabetes (n = 198) had thicker LV posterior walls (aMD 0.19 mm; 95% CI 0.11, 0.27), smaller LV internal diameters in systole (aMD -0.27 mm; 95% CI -0.45, -0.18) and diastole (aMD -0.37 mm; 95% CI -0.59, -0.09), reduced stroke volumes (aMD -0.36 mL; 95% CI -0.61, -0.11), and increased heart rates (aMD 3.14 bpm; 95% CI 1.10, 6.18) and mitral valve early peak velocities (aMD 2.17 cm/s; 95% CI 0.31, 4.04) than unexposed infants (n = 24,639). Infants born to mothers with GDM (n = 649) had significantly smaller LV internal diameters in systole (aMD -0.13 mm; 95% CI -0.22, -0.03) and similar structural and functional changes as children exposed to preexisting diabetes, albeit with smaller nonsignificant aMDs. Higher third-trimester HbA1c levels were associated with smaller LV internal diameters and stroke volumes in infants exposed to preexisting diabetes and with lower heart rates in infants exposed to GDM. Maternal preexisting diabetes and, to a lesser extent, GDM were associated with changes in infant LV structure and function.

Associations between glycated haemoglobin and multi-modal imaging markers of early cardiac aging.

Glycated haemoglobin (HbA1c) is a well-established biomarker for diabetes diagnosis and management and is linked to risk of cardiovascular death. However, among adults without cardiovascular disease (CVD) and diabetes, the value of HbA1c in predicting distinct signatures of myocardial ageing has not been explored. Subjects, from among older adults without CVD, underwent comprehensive cardiovascular and metabolic assessment. Transthoracic echocardiography measured left ventricular structure and function. Longitudinal left atrial (LA) strain comprising reservoir strain (Ɛs), conduit strain (Ɛe) and booster strain (Ɛa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using cardiac magnetic resonance (CMR). Blood sampling for biomarkers and cardiovascular examinations were performed. 247 subjects (mean age 71years, 44.1% female, mean HbA1c 6.0%) were included. HbA1c was significantly associated with E/A ratio (p < 0.0001), conduit strain (Ɛe) (p < 0.0001), conduit strain rate SRe (p < 0.0001), and conduit strain rate to booster strain rate SRe:SRa ratio (p < 0.0001). Multivariate models adjusting for clinical variables such as body mass index, blood pressure, heart rate, diabetes mellitus, smoking, and associated cardiac parameters, demonstrated a persistent independent association. Each unit increase in HbA1c was associated with lower E/A ratio, lower Ɛe, higher SRe and lower SRe:SRa ratio. These associations remained significant after diabetic subjects were excluded. Distinct associations were found between HbA1c and myocardial functions of interest in the ageing heart. HbA1c may be useful biomarker for stratifying risks associated with myocardial ageing, independent of diabetes status. ClinicalTrials.gov Identifier: NCT02791139.

Concept, study design, and baseline nighttime blood pressure control status of the WISDOM-Night Study using a wrist-type oscillometric home blood pressure monitoring device.

There is growing evidence that nocturnal hypertension is an independent risk factor for cardiovascular diseases, including heart failure. However, brachial blood pressure (BP) measurements during sleep might themselves disturb sleep quality. We initiated a nationwide, multicenter observational prospective study using a wrist-type oscillometric nighttime BP monitoring device with new algorithms to measure supine BP accurately without sleep disturbance. This study, named the Wrist ICT-based Sleep and Circadian Blood Pressure Monitoring Program-Night BP Study (WISDOM-Night Study), was designed to clarify the impact of wrist-measured daily nighttime BPs on cardiovascular prognosis (stroke, coronary artery disease, heart failure, etc.) using 7 days of BP measurements at 2:00 a.m., 3:00 a.m., 4:00 a.m., and 4 h after bedtime. A total of 2751 patients with one or more cardiovascular risk factors were recruited between March 2021 and March 2024 and are currently being followed up for 7 years. Additionally, 1416 of the WISDOM-Night Study-enrolled patients who also agreed to participate in the WISDOM-Hypertension-Mediated Organ Damage (HMOD) Study underwent echocardiography to evaluate the association between wrist-measured BP and left ventricular structure. Data from this WISDOM-Night Study should provide the prospective association between nighttime BP and cardiovascular disease and reveal the indexes of nighttime BP with clinical pathological relevance. This first report of the WISDOM-Night Study describes the study design, baseline characteristics, and BP control status.

6870 Cardiac Imaging And Metabolomics Studies Suggest Differential Risk And Protective Biomarkers For Cardiovascular Disease In Renoprotected, Long-Duration Type 1 Diabetes

Abstract Disclosure: M. Yu: None. S. Jangolla: None. N. Ziemniak: None. E. Viebranz: None. T. Chokshi: None. K. Park: None. I. Wu: None. H. Shah: None. G.L. King: None. Cardiovascular disease (CVD) is a major cause of mortality in people with Type 1 diabetes (T1D), especially in those with nephropathy (DN). However, in long-duration T1D, a substantial proportion of individuals without DN still exhibit excessive CVD risks. The Joslin 50-Year “Medalist” Study (n=1043), composed of people with T1D≥50 years, are ideal for studying CVD in a renoprotected T1D cohort, as only 13% have DN, and yet 40% have CVD, despite excellent control of lipids and blood pressure. Stratifying the Medalists by DN revealed that exercise was cardioprotective in the group with DN (OR 0.60, p=0.04); while age at T1D diagnosis (OR 1.03, p=0.01), HbA1c (OR 1.25, p=0.01), C-reactive protein (OR 1.14, p=0.01), and interleukin-6 (OR 1.13, p=0.01) all increased CVD risk in Medalists without DN. A subset of Medalists also underwent coronary artery calcification scans (CAC; n=153) and cardiac magnetic resonance imaging of left ventricular (LV) structure and function (CMR; n=111). The majority of these Medalists (97.8%) had detectable CAC&amp;gt;0; furthermore, the median CAC score of 1000 was higher at any cutoff compared to similar age-matched T1D and Type 2 diabetes (T2D) populations with higher DN prevalence. In contrast, mean CMR values in this Medalist subset were comparable to other cohorts. Continuous glucose monitoring (CGM) metrics for hyperglycemia (mean glucose, β=0.002, p=0.03; glucose management indicator, β=0.09, p=0.03; and time above range&amp;gt;180 mg/dL, β=0.003, p=0.02), but not glucose variability or hypoglycemia, were associated with LV remodeling in the Medalists, even after adjusting for eGFR. Likewise, plasma levels of advanced glycation end-products (AGEs) N-carboxyethyl-lysine (CEL), N-carboxymethyl-lysine (CML), and methylglyoxal-derived hydroimidazolone (MGH1) were associated with CAC (β=16.22, p=0.05; β=15.21, p=0.01; and β=10.18, p=0.01, respectively) and LV remodeling (β=0.001, p=0.09; β=0.001, p=0.05; and β=0.001, p=0.04, respectively) in the Medalists. The association of CEL with CVD replicated in a separate Medalist subset (n=311) with self-reported CVD data (OR 1.26, p=0.01). Plasma global metabolomics studies (n=140) revealed that amino acid activation pathways, with lower levels of branched chain amino acids, were associated with CAC (FDR=0.002); while amino acid metabolism pathways were associated with less favorable LV volumes (FDR=0.03). In this comprehensive study of aging T1D people with no substantial DN, hyperlipidemia, or hypertension, cardiac imaging and metabolomics studies suggest disproportionate advanced CAC, as compared to subclinical LV remodeling or dysfunction, and highlight the importance of targeting hyperglycemia for CVD risk reduction. Plasma metabolites associated with CVD in T1D are different from those in T2D, and may provide novel information on potential therapeutic targets for CVD in T1D. Presentation: 6/1/2024

Maternal hypertensive disorders of pregnancy and electrocardiographic findings among newborns: The Copenhagen Baby Heart Study.

Maternal preeclampsia is associated with both congenital heart defects and changes in left ventricular structure and function in the offspring. Whether preeclampsia and gestational hypertension also affect the offspring's cardiac conduction system is unknown. This study assesses whether infants exposed to maternal hypertensive disorders of pregnancy (HDPs) exhibit changes in their electrocardiogram (ECG) compared with infants unexposed to HDPs. This population-based cohort study included newborns from the Copenhagen Baby Heart Study who had an ECG performed within 30 days of birth and had available obstetric information. ECG parameters of newborns exposed to maternal HDPs were compared with those of unexposed newborns using linear regression. Our study cohort included 11,826 newborns, including 441 exposed to maternal preeclampsia and 320 exposed to gestational hypertension. Infants exposed to preeclampsia had prolonged QRS durations (adjusted mean difference 0.6 ms, 95% confidence interval [CI] 0.04, 1.16) and lower maximum amplitudes of the R-wave in V1 (adjusted mean difference, linear scale 0.95, 95% CI 0.90, 1.00), compared with unexposed infants. Exposure to maternal preeclampsia was not associated with changes in other ECG parameters. Exposure to gestational hypertension was associated with increased QT interval durations (QTc Bazett, adjusted mean difference 2.48 ms, 95% CI -0.23, 5.20; QTc Fridericia, adjusted mean difference 2.32 ms, 95% CI -0.19, 4.83). Our findings suggest that the newborn cardiac conduction system is affected by exposure to maternal preeclampsia. This could reflect the previously described thickening of the left ventricular myocardium in infants exposed to preeclampsia.

Expression of HMGB1, TGF-β1, BIRC3, ADAM17, CDKN1A, and FTO in Relation to Left Ventricular Remodeling in Patients Six Months after the First Myocardial Infarction: A Prospective Study.

Background: After myocardial infarction (MI), adverse left ventricular (LV) remodeling may occur. This is followed by LV hypertrophy and eventually heart failure. The remodeling process is complex and goes through multiple phases. The aim of this study was to investigate the expression of HMGB1, TGF-β1, BIRC3, ADAM17, CDKN1A, and FTO, each involved in a specific step of LV remodeling, in association with the change in the echocardiographic parameters of LV structure and function used to assess the LV remodeling process in the peripheral blood mononuclear cells (PBMCs) of patients six months after the first MI. The expression of selected genes was also determined in PBMCs of controls. Methods: The study group consisted of 99 MI patients, who were prospectively followed-up for 6 months, and 25 controls. Cardiac parameters, measured via conventional 2D echocardiography, were evaluated at two time points: 3-5 days and 6 months after MI. The mRNA expression six-months-post-MI was detected using TaqMan® technology (Applied Biosystems, Thermo Fisher Scientific, Waltham, MA, USA). Results:HMGB1 mRNA was significantly higher in patients with adverse LV remodeling six-months-post-MI than in patients without adverse LV remodeling (p = 0.04). HMGB1 mRNA was significantly upregulated in patients with dilated LV end-diastolic diameter (LVEDD) (p = 0.03); dilated LV end-diastolic volume index (LVEDVi) (p = 0.03); severely dilated LV end-systolic volume index (LVESVi) (p = 0.006); impaired LV ejection fraction (LVEF) (p = 0.01); and LV enlargement (p = 0.03). It was also significantly upregulated in PBMCs from patients compared to controls (p = 0.005). TGF-β1 and BIRC3 mRNA were significantly lower in patients compared to controls (p = 0.02 and p = 0.05, respectively). Conclusions: Our results suggest that HMGB1 is involved in adverse LV remodeling six-months-post-MI, even on the mRNA level. Further research and validation are needed.

NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study.

Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized. Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines. Models were adjusted for age, sex, race, body mass index, smoking, diabetes, hypertension, and renal function at visit 5; blood pressure and heart rate at both visits; and the baseline value of the echocardiographic parameter of interest. Mean±SD age was 74±4 years at visit 5; 61% were women; and 23% were Black adults. Median (25th-75th percentile) concentrations at visit 5 of NT-proBNP, hs-cTnT, and hs-cTnI were 87 ng/L (50-157 ng/L), 9 ng/L (6-12 ng/L), and 2.6 ng/L (1.9-3.9 ng/L). In adjusted models, elevated baseline concentrations of NT-proBNP and hs-cTnI were significantly associated with 7-year decline in left ventricular systolic function (ejection fraction, longitudinal and circumferential strain) and worsening diastolic indices. In contrast, elevated baseline concentrations of hs-cTnT were not significantly associated with 7-year changes in cardiac structure, systolic function, or diastolic function (all P>0.05). Higher concentrations of NT-proBNP and hs-cTnI, but not hs-cTnT, were associated with greater declines in left ventricular function over ≈7 years in late life independently of traditional cardiovascular risk factors.AQ.

Associations between visceral and liver fat and cardiac structure and function: a UK Biobank study.

Different fat depots have connected to cardiovascular health. We assessed the associations of abdominal magnetic resonance-quantified visceral adipose tissue (VAT) and liver fat (proton density fat fraction, PDFF) with cardiac magnetic resonance (CMR)-measured cardiac structure and function, and considered potential mechanism. Our study encompassed 10,920 participants from the UK Biobank. We utilized multiple linear regression and multiple mediation analyses to estimate the connections between VAT or PDFF and CMR metrics. Elevated VAT or PDFF exhibited associations with adverse left ventricular (LV) structure (increased wall thickness, concentric LV remodeling), impaired LV function (lower LV global functional index, absolute value of LV global longitudinal strain), and diminished left atrial volumes and stroke volume (all p-values were significant）. Upon stratifying participants based on VAT and PDFF combinations, all groups, except the low VAT-low PDFF group, were linked to unfavorable cardiac remodeling metrics. The high VAT-high PDFF group displayed the most pronounced cardiac alterations. Multiple mediation analyses were employed to investigate potential mediating roles of systolic blood pressure (SBP), diabetes, dyslipidemia and blood biomarkers (lipidemia, transaminases) in the adipose-CMR relationship. The findings suggested that VAT or PDFF was related to SBP, diabetes, dyslipidemia, lipid profile, liver function, and glucose. Several potential mediating pathways were identified, primarily through SBP and triglyceride-glucose index, which only partially explained the adipose-CMR relationship. We established the independent associations of VAT and PDFF with unhealthy cardiac structure and function. Furthermore, it identifies SBP and insulin resistance as important mediating factors.

Subclinical left ventricular structural and functional alterations in children with obesity: is body mass or insulin resistance the main issue?

Obesity is an independent risk factor for cardiovascular diseases. The study aims to assess the left ventricular structure and functions in children with obesity. This study included 29 patients with metabolic syndrome, 31 patients with obesity without metabolic syndrome, and 30 healthy children of similar age and gender. Demographic, anthropometric, and biochemical findings and left ventricular structure and functions evaluated by conventional pulsed wave Doppler and tissue Doppler echocardiography were compared. The left ventricular mass index and relative wall thickness were significantly higher in children with obesity compared to controls. The mean left ventricular mass index of children with metabolic syndrome was also higher than for those without it. Most children with obesity had normal left ventricular geometry; concentric hypertrophy (27.6%) was more common in children with metabolic syndrome, and eccentric hypertrophy (25.7%) was more common in those without. The early to late diastolic mitral annular velocity ratios obtained with conventional pulsed wave Doppler echocardiography and tissue Doppler echocardiography (E/A and Em/Am, respectively) were lower in children with obesity than controls. In addition, the ratio obtained by tissue Doppler echocardiography was lower in children with metabolic syndrome than without. The homeostatic model assessment of insulin resistance, systolic blood pressure, and body mass index has been identified as independent factors for left ventricular structures and functions. Obesity causes subclinical left ventricular hypertrophy and diastolic dysfunction. Additional metabolic syndrome-related risks lead to further deterioration of cardiac morphology and functions.

Proteomics of left ventricular structure in the Multi-Ethnic Study of Atherosclerosis.

Proteomic profiling offers an expansive approach to biomarker discovery and mechanistic hypothesis generation for LV remodelling, a critical component of heart failure (HF). We sought to identify plasma proteins cross-sectionally associated with left ventricular (LV) size and geometry in a diverse population-based cohort without known cardiovascular disease (CVD). Among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we quantified plasma abundances of 1305 proteins using an aptamer-based platform at exam 1 (2000-2002) and exam 5 (2010-2011) and assessed LV structure by cardiac magnetic resonance (CMR) at the same time points. We used multivariable linear regression with robust variance to assess cross-sectional associations between plasma protein abundances and LV structural characteristics at exam 1, reproduced findings in later-life at exam 5, and explored relationships of associated proteins using annotated enrichment analysis. We studied 763 participants (mean age 60±10years at exam 1; 53% female; 19% Black race; 31% Hispanic ethnicity). Following adjustment for renal function and traditional CVD risk factors, plasma levels of 3 proteins were associated with LV mass index at both time points with the same directionality (FDR<0.05): leptin (LEP), renin (REN), and cathepsin-D (CTSD); 20 with LV end-diastolic volume index: LEP, NT-proBNP, histone-lysine N-methyltransferase (EHMT2), chordin-like protein 1 (CHRDL1), tumour necrosis factor-inducible gene 6 protein (TNFAIP6), NT-3 growth factor receptor (NTRK3), c5a anaphylatoxin (C5), neurogenic locus notch homologue protein 3 (NOTCH3), ephrin-B2 (EFNB2), osteomodulin (OMD), contactin-4 (CNTN4), gelsolin (GSN), stromal cell-derived factor 1 (CXCL12), calcineurin subunit B type 1 (PPP3R1), insulin-like growth factor 1 receptor (IGF1R), bone sialoprotein 2 (IBSP), interleukin-11 (IL-11), follistatin-related protein 1 (FSTL1), periostin (POSTN), and biglycan (BGN); and 4 with LV mass-to-volume ratio: RGM domain family member B (RGMB), transforming growth factor beta receptor type 3 (TGFBR3), ephrin-A2 (EFNA2), and cell adhesion molecule 3 (CADM3). Functional annotation implicated regulation of the PI3K-Akt pathway, bone morphogenic protein signalling, and cGMP-mediated signalling. We report proteomic profiling of LV size and geometry, which identified novel associations and reinforced previous findings on biomarker candidates for LV remodelling and HF. If validated, these proteins may help refine risk prediction and identify novel therapeutic targets for HF.

Mas receptor blockade impairs exercise-induced cardiac hypertrophy

Exercise training leads to physiological cardiac hypertrophy and the protective axis of the renin-angiotensin system composed of angiotensin-converting enzyme 2, angiotensin-(1–7), and Mas receptor seems involved in this process. However, the role of the basal activity of the Mas receptor in exercise-induced physiological cardiac hypertrophy is still unclear. We evaluated the effects of the Mas receptor blockade on the left ventricular structure and function of rats submitted to running training. Rats were assigned to 4 groups: sedentary (S), sedentary + A-779 (Mas receptor antagonist, 120 µg/kg/day, i.p.; SA), trained (60-minute treadmill running sessions, five days a week, 8 weeks; T), and trained + A-779 (TA). Systolic blood pressure was higher in sedentary and trained rats treated with A-779 at the end of the experimental period. The A-779 treatment prevented the left ventricular hypertrophy evoked by physical exercise and increased collagen deposition in sedentary and trained rats. Cardiomyocytes from the SA group presented increased length and thickness of the sarcomeres, elongated mitochondria, glycogen deposits, and enlarged cisterns of the sarcoplasmic reticulum. TA group presented a reduced sarcomere thickness and cytoplasm with a degenerative aspect. These findings show that the basal activity of the Mas receptor is essential for the proper turnover of the extracellular matrix in the myocardium and the maintenance of the sarcomeric structure of cardiomyocytes.