Left Ventricular Diastolic Dysfunction Research Articles

The effect of hyperlipidemia and body fat distribution on subclinical left ventricular function in obesity: a cardiovascular magnetic resonance study

BackgroundObesity is often associated with multiple comorbidities. However, whether obese subjects with hyperlipidemia in the absence of other complications have worse cardiac indices than metabolically healthy obese subjects is unclear. Therefore, we aimed to determine the effect of hyperlipidemia on subclinical left ventricular (LV) function in obesity and to evaluate the association of cardiac parameters with body fat distribution.Materials and methodsNinety-two adults were recruited and divided into 3 groups: obesity with hyperlipidemia (n = 24, 14 males), obesity without hyperlipidemia (n = 25, 13 males), and c ntrols (n = 43, 25 males). LV strain parameters (peak strain (PS), peak diastolic strain rate (PDSR), peak systolic strain rate) derived from cardiovascular magnetic resonance tissue tracking were measured and compared. Dual-energy X-ray absorptiometer was used to measure body fat distribution. Correlations of hyperlipidemia and body fat distribution with LV strain were assessed by multivariable linear regression.ResultsObese individuals with preserved LV ejection fraction showed lower global LV longitudinal, circumferential, and radial PS and longitudinal and circumferential PDSR than controls (all P < 0.05). Among obese patients, those with hyperlipidemia had lower longitudinal PS and PDSR and circumferential PDSR than those without hyperlipidemia (− 12.8 ± 2.9% vs. − 14.2 ± 2.7%, 0.8 ± 0.1 s−1 vs. 0.9 ± 0.3 s−1, 1.2 ± 0.2 s−1 vs. 1.4 ± 0.2 s−1; all P < 0.05). Multivariable linear regression demonstrated that hyperlipidemia was independently associated with circumferential PDSR (β = − 0.477, P < 0.05) in obesity after controlling for growth differences, other cardiovascular risk factors, and central fat distribution. In addition, android fat had an independently negative relationship with longitudinal and radial PS (β = − 0.486 and β = − 0.408, respectively; all P < 0.05); and visceral fat was negatively associated with longitudinal PDSR (β = − 0.563, P < 0.05). Differently, gynoid fat was positively correlated with circumferential PS and PDSR and radial PDSR (β = 0.490, β = 0.481, and β = 0.413, respectively; all P < 0.05).ConclusionHyperlipidemia is independently associated with subclinical LV diastolic dysfunction in obesity. Central fat distribution (android and visceral fat) has a negative association, while peripheral fat distribution (gynoid fat) has a positive association on subclinical LV function. These results suggest that appropriate management of hyperlipidemia may be beneficial for obese patients, and that the differentiation of fat distribution in different regions may facilitate the precise management of obese patients.Clinical trials registration Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476).

Types of Septic Cardiomyopathy: Prognosis and Influencing Factors - A Clinical Study.

To explore the prognostic outcomes associated with different types of septic cardiomyopathy and analyze the factors that exert an influence on these outcomes. The data collected within 24 hours of ICU admission included cardiac troponin I (cTnI), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP); SOFA (sequential organ failure assessment) scores, and the proportion of vasopressor use. Based on echocardiographic outcomes, septic cardiomyopathy was categorized into left ventricular (LV) systolic dysfunction, LV diastolic dysfunction, and right ventricular (RV) systolic dysfunction. Differences between the mortality and survival groups, as well as between each cardiomyopathy subgroup and the non-cardiomyopathy group were compared, to explore the influencing factors of cardiomyopathy. A cohort of 184 patients were included in this study, with LV diastolic dysfunction having the highest incidence rate (43.5%). The mortality group had significantly higher SOFA scores, vasopressor use, and cTnI levels compared to the survival group; the survival group had better LV diastolic function than the mortality group (p < 0.05 for all). In contrast to the non-cardiomyopathy group, each subgroup within the cardiomyopathy category exhibited elevated levels of cTnI. The subgroup with left ventricular diastolic dysfunction demonstrated a higher prevalence of advanced age, hypertension, diabetes mellitus, coronary artery disease, and an increased mortality rate; the RV systolic dysfunction subgroup had higher SOFA scores and NT-proBNP levels, and a higher mortality rate (P < 0.05 for all); the LV systolic dysfunction subgroup had a similar mortality rate (P > 0.05). Patients with advanced age, hypertension, diabetes mellitus, or coronary artery disease are more prone to develop LV diastolic dysfunction type of cardiomyopathy; cardiomyopathy subgroups had higher levels of cTnI. The RV systolic dysfunction cardiomyopathy subgroup had higher SOFA scores and NT-proBNP levels. The occurrence of RV systolic dysfunction in patients with sepsis significantly increased the mortality rate.

Non-invasive assessment of left ventricular filling pressure in aortic stenosis.

The assessment of left ventricular (LV) filling pressure (FP) is important for the management of aortic stenosis (AS) patients. Although, it is often restricted for predict LV FP in AS because of mitral annular calcification and a certain left ventricular hypertrophy. Thus, we tested the predictive ability of the algorithm for elevated LV FP in AS patients and also applied a recently-proposed echocardiographic scoring system of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score. We enrolled consecutive 116 patients with at least moderate AS in sinus rhythm who underwent right heart catheterization and echocardiography within 7 days. Mean pulmonary artery wedge pressure (PAWP) was measured as invasive parameter of LV FP. LV diastolic dysfunction (DD) was graded according to the ASE/EACVI guidelines. The VMT score was defined as follows: time sequence of opening of mitral and tricuspid valves was scored to 0-2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). When the inferior vena cava was dilated, one point was added and VMT score was finally calculated as 0-3. Of the 116 patients, 29 patients showed elevated PAWP. Ninety patients (93%) and 67 patients (63%) showed increased values for left atrium volume index (LAVI) and E/e', respectively when the cut-off values recommended by the guidelines were applied and thus the algorism predicted elevated PAWP with a low specificity and positive predictive value (PPV). VMT≥2 predicted elevated PAWP with a sensitivity of 59%, specificity of 90%, PPV of 59%, and negative predictive value of 89%. An alternative algorithm that applied tricuspid regurgitation velocity and VMT scores was tested, and its predictive ability was markedly improved. VMT score was applicable for AS patients. Alternative use of VMT score improved diagnostic accuracy of guideline-recommended algorism.

Allele-specific dysregulation of lipid and energy metabolism in early-stage hypertrophic cardiomyopathy

IntroductionHypertrophic cardiomyopathy (HCM) results from pathogenic variants in sarcomeric protein genes that increase myocyte energy demand and lead to cardiac hypertrophy. However, it is unknown whether a common metabolic trait underlies cardiac phenotype at the early disease stage. To address this question and define cardiac biochemical pathology in early-stage HCM, we studied two HCM mouse models that express pathogenic variants in cardiac troponin T (Tnt2) or myosin heavy chain (Myh6) genes, and have marked differences in cardiac imaging phenotype, mitochondrial function at early disease stage. MethodsWe used a combination of echocardiography, transcriptomics, mass spectrometry-based untargeted metabolomics (GC-TOF, HILIC, CSH-QTOF), and computational modeling (CardioNet) to examine cardiac structural and metabolic remodeling at early disease stage (5 weeks of age) in R92W-TnT+/− and R403Q-MyHC+/− mutant mice. Data from mutants was compared with respective littermate controls (WT). ResultsAllele-specific differences in cardiac phenotype, gene expression and metabolites were observed at early disease stage. LV diastolic dysfunction was prominent in TnT mutants. Differentially-expressed genes in TnT mutant hearts were predominantly enriched in the Krebs cycle, respiratory electron transport, and branched-chain amino acid metabolism, whereas MyHC mutants were enriched in mitochondrial biogenesis, calcium homeostasis, and liver-X-receptor signaling. Both mutant hearts demonstrated significant alterations in levels of purine nucleosides, trisaccharides, dicarboxylic acids, acylcarnitines, phosphatidylethanolamines, phosphatidylinositols, ceramides and triglycerides; 40.4 % of lipids and 24.7 % of metabolites were significantly different in TnT mutants, whereas 10.4 % of lipids and 5.8 % of metabolites were significantly different in MyHC mutants. Both mutant hearts had a lower abundance of unsaturated long-chain acyl-carnitines (18:1, 18:2, 20:1), but only TnT mutants showed enrichment of FA18:0 in ceramide and cardiolipin species. CardioNet predicted impaired energy substrate metabolism and greater phospholipid remodeling in TnT mutants than in MyHC mutants. ConclusionsOur systems biology approach revealed marked differences in metabolic remodeling in R92W-TnT and R403Q-MyHC mutant hearts, with TnT mutants showing greater derangements than MyHC mutants, at early disease stage. Changes in cardiolipin composition in TnT mutants could contribute to impairment of energy metabolism and diastolic dysfunction observed in this study, and predispose to energetic stress, ventricular arrhythmias under high workloads such as exercise.

Management of hypertension in heart transplant recipients: an ongoing conundrum.

Hypertension remains one of the most common clinical problems leading to significant posttransplant complications. This study reviews the pathophysiology of hypertension in the postcardiac transplant phase and provides an update on currently available antihypertensive therapies for heart transplant patients. The true prevalence of hypertension in the heart transplant population remains unknown. Effective blood pressure (BP) control is key to prevent left ventricular remodeling, diastolic dysfunction and stroke. Calcium channel blockers (CCBs) are the most commonly and preferred agents in the early posttransplant phase and may have renal protective effects. Angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) can all be used as second line antihypertensive agents and may have a role in preventing other long-term complications such as calcineurin-inhibitor induced nephropathy. Although more data are needed, sodium-glucose co-transporter 2 inhibitors (SGLT2i) appeared to be well tolerated and could be considered especially in the presence of type diabetes and chronic kidney disease. Conversely, angiotensin receptor-neprilysin inhibition (ARNI) have not been studied in the heart transplant population therefore cannot be recommended at this time. Hypertension is very common after heart transplant. Early steroid wean and traditional risk factor modification play an important part in the management of post-heart transplant hypertension. CCB, ACEI, ARB are the preferred antihypertensive agents to improve postcardiac transplant complications. Novel therapies such as SGLT2i appear well tolerated and may have benefits in both BP and glycemic control in heart transplant; however, larger trials are needed.

The Influence of Pericardial Fat on Left Ventricular Diastolic Function.

Heart failure is a major cause of morbidity and mortality worldwide; left ventricular diastolic dysfunction plays a leading role in this clinical context. Diastolic dysfunction may be predisposed by increased abdominal fat and, consequently, increased pericardial and epicardial adiposity. This study aimed to determine whether pericardial fat (PF) and epicardial fat (EF) are associated with left ventricular diastolic function. A total of 82 patients had their abdominal circumference measured and underwent transthoracic echocardiography to measure the thickness of PF and EF and assess the left ventricular diastolic function. Two groups were created based on mean pericardial fat (PF) thickness (4.644 mm) and were related to abdominal circumference and echocardiographic parameters. Subjects in the PF High group showed a significant decrease in septal e' (p < 0.0001), lateral e' (p < 0.0001), and E/A ratio (p = 0.003), as well as a significant increase in E/e' ratio (p < 0.0001), E wave deceleration time (p = 0.013), left atrial volume (p < 0.0001), the left ventricle mass (p = 0.003), tricuspid regurgitant jet velocity (p < 0.0001), and the left ventricle diameter (p = 0.014) compared to the PF Low group. Correlations were found between pericardial fat and nine echocardiographic parameters in the study, while epicardial fat (EP) only correlated with eight. Measurement of abdominal circumference, PF, and EF is an early indicator of diastolic changes with transthoracic echocardiography being the gold standard exam.

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.

Association of left ventricular diastolic function with parameters of arterial stiffness and atherosclerotic plaques in the carotid basin in hypertensive patients

Aim. Тo assess changes in the left ventricular diastolic dysfunction (LVDD) indicators depending on the elastic properties of the common carotid arteries (CCA) and the presence of atherosclerotic plaque (ASP) in patients with stage II hypertension (HTS). Materials and methods. 48 patients with stage II HTS were involved in the study, the average age was 55.9 ± 11.2, 45.8 % men, among whom 14 did not have LVDD, 34 – had type I LVDD; 25 people did not have ASP, 23 people had ASP. Basic anthropometric data, echocardiographic indicators, QIMT, local stiffness indicators were studied: arterial diameter, distensibility, DC, CC, stiffness indices α, β, local PWV, augmentation pressure and index (using RF-QIMT, RF-QAS technologies). Statistical analysis was performed, the probability of differences is at the level of p &lt; 0.05. Results. Significant differences in the stiffness parameters of the common carotid arteries were observed in patients with stage II HTS with LVDD: the diameter of the artery is higher by 6.5 % (p = 0.032), the stiffness index α – 28.3 % (р = 0.008), stiffness index β – 28.1 % (р = 0.009), PWV – 9.8 % (р = 0.004), DC is lower by 50.0 % (р = 0.021). A negative correlation of average strength was observed between e’med, e’lat, e’tv and stiffness indices α, β and PWV; E/e’, e’lat, e’tv had the average strength positive correlation with DC, CC indicators. The diameter of the carotid artery had a positive medium strength correlation with the thickness of the IVS (r = +0.38), LVFW (r = +0.47), RWT (r = +0.32), and LVMI (r = +0.57), diameter of the LA (r = +0.50) and had significant differences between 4 types of LV remodeling. The odds ratio of ASP in CCA increases by 1.32 times (p = 0.038) in the case of an excess of a’med more than 7 cm/c (sensitivity 95.7 %, specificity 28.0 %, p = 0.038); the influence of factor increases with a simultaneous increase in the diameter of the CCA over 7.94 mm (sensitivity 59.1 %, specificity 81.6 %, p = 0.005), and this prognostic model does not depend on age andgender. Conclusions. In persons with stage II HTS, the presence of type I LVDD is associated with an increase in the local stiffness and diameter of the CCA, just as the presence of ASP is associated with worse indicators of LVDD, in particular, a significant increase in a’med, regardless of age and gender.

Impact on carotid intima-media thickness after laparoscopic sleeve gastrectomy in patients with morbid obesity.

We aimed to investigate the impact of laparoscopic sleeve gastrectomy (LSG) on carotid intima-media thickness (CIMT) & left ventricular dysfunction (LVD) which are the independent predictors of subclinical atherosclerosis. To assess the change in CIMT & echocardiographic parameters of left ventricular function & correlate with %EWL 6months and 12months after LSG, the mean CIMT of bilateral common carotid arteries were measured at 3 different places & 7 parameters were assessed for left ventricular dysfunction after 6 and 12months of LSG & correlated with the %EWL. A total of 30 patients (27(90%) women & 3(10%) men) with the mean age of 38 ± 7.84 were prospectively enrolled. BMI was significantly reduced from 42.66 ± 3.79 to 37.93 ± 3.60kg/m2 at six months to 36 ± 3.34 at 12months after LSG. CIMT values were significantly decreased at 6months after surgery from 0.50 ± 0.11mm to 0.46 ± 0.09mm (p < 0.01) to 0.39 ± 0.07 (p < 0.05) at 12months. However, no significant change was observed in the right mean CCA values at 6months after surgery 0.50 ± 0.11mm vs 0.47 ± 0.09mm (p = 0.07) as compared to decrease at 12months after surgery to 0.40 ± 0.08 (p < 0.05). Left mean CCA values at 6months changed from 0.50 ± 0.11 to 0.45 ± 0.09 (p < 0.01) and at 12months after surgery to 0.39 ± 007(p < 0.05). On 2D ECHO, ejection fraction increased at 6months from 60.80 ± 5.89 to 61.93 ± 4.47 (p < 0.5) to after 12months at 64.30 ± 4.20 (p < 0.05). Wave deceleration time changed at 6months from 170 ± 36.80 to 150 ± 28.82 (p < 0.05) to 12months 139.07 ± 17.98 (p < 0.05). Peak early diastolic mitral annular velocity (e) changed at 6months from 8.12 ± 1.66 to 7.02 ± 1.76 (p < 0.05) to 12months 6.33 ± 0.76 (p < 0.05). Inter-ventricular septum thickness (IVSD) changed at 6months from 0.99 ± 0.14 to 0.91 ± 0.14 (p < 0.05) to 12months 0.82 ± 0.09 (p < 0.05). Intraventricular relaxation time (IVRT) at 6months changed from 94.33 ± 21.71 to 84.36 ± 14.85 (p < 0.03) to 12months after surgery 77.40 ± 10.19 (p < 0.05). Left atrial volume index (LAVI) at 6months decreased from 38.08 ± 11.23 to 30.93 ± 7.16 (p < 0.01) to 12months after surgery 25.43 ± 3.65 (p < 0.05). Left ventricular diastolic dysfunction [LVIDD] at 6months changed from 4.32 ± 0.52 to 4.11 ± 0.52 (p < 0.02) to 3.94 ± 0.26 (p < 0.05) to 3.94 ± 0.26 (p < 0.05) at 12months after surgery. PwD at 6 and 12months changed from 1.00 ± 0.19 to 0.87 ± 0.10 (p < 0.01) to 0.82 ± 0.08 (p < 0.05) respectively. LV mass changed in 6months from 148.37 ± 33.09 to 117 ± 29.90 (p < 0.001) to 12months at 110.64 ± 20.79 (p < 0.05) and left ventricular mass index [LVMI] changed in 6months from 70 ± 16.89 to 59.626 ± 15.35 (p < 0.001) reaching a value of 57.53 ± 11.18 (p < 0.05) at 12months. The mean 10-year risk of death due to CVD calculated was significantly reduced from 5.45 ± 6.6 to 2.8 ± 1.7% at 6months (p < 0.05). This significant decrease in CVD risk has a positive correlation with the decrease in CIMT over 6months showing a correlation coefficient of 0.018 with statistically significant analysis (p value < 0.05). We observed a significant reduction in CIMT & improvement in 2D ECHO parameters at 6 after LSG although no statistically significant change was observed in mean right CIMT & EF at 6months.

Association of serum galectin-3 levels with mortality and cardiovascular disease outcomes in hemodialysis patients: a systematic review and dose-response meta-analysis.

Galectin-3 has been proposed as a candidate marker for cardiovascular risk stratification, although its role in kidney failure is unclear. The aim of this systematic review was to assess the association of serum galectin-3 levels with overall survival and cardiovascular outcomes among hemodialysis patients. Medline, Scopus, Web of Science and CENTRAL were systematically searched from inception till Aug 20, 2023. Observational studies evaluating the association of serum galectin-3 with mortality, cardiovascular disease and arterial stiffness in hemodialysis patients were included. The exposure-response relationship between galectin-3 and mortality was explored by dose-response meta-analysis using restricted cubic splines in a one-stage approach. Overall, 13 studies were included (9 cohort and 4 cross-sectional), comprising 6025 hemodialysis individuals. Increasing galectin-3 values were associated with greater all-cause mortality risk (χ2: 18.71, p-value < 0.001) and an insignificant trend toward higher cardiovascular mortality risk (χ2: 5.06, p-value: 0.079). Compared to a reference galectin-3 value of 10ng/ml, all-cause mortality risk was significantly higher with levels of 20ng/ml (Hazard ratio-HR: 2.62, 95% confidence intervals-CI: 1.66-4.15), 30ng/ml (HR: 3.78, 95% CI: 2.05-6.97) and 40ng/ml (HR: 4.01, 95% CI: 2.14-7.52). Qualitative synthesis of evidence indicated that serum galectin-3 may be linked to abdominal aortic calcification severity and progression, as well as to left ventricular systolic and diastolic dysfunction. This study suggests that high serum galectin-3 levels are associated with greater all-cause mortality risk among patients on maintenance hemodialysis. Preliminary cross-sectional evidence indicates that serum galectin-3 may be associated with arterial stiffness and left ventricular dysfunction.

The cardiovascular changes underlying a low cardiac output with exercise in patients with type 2 diabetes mellitus.

The significant morbidity and premature mortality of type 2 diabetes mellitus (T2DM) is largely associated with its cardiovascular consequences. Focus has long been on the arterial atheromatosis of DM giving rise to early stroke and myocardial infarctions, whereas less attention has been given to its non-ischemic cardiovascular consequences. Irrespective of ischemic changes, T2DM is associated with heart failure (HF) most commonly with preserved ejection fraction (HFpEF). Largely due to increasing population ages, hypertension, obesity and T2DM, HFpEF is becoming the most prevalent form of heart failure. Unfortunately, randomized controlled trials of HFpEF have largely been futile, and it now seems logical to address the important different phenotypes of HFpEF to understand their underlying pathophysiology. In the early phases, HFpEF is associated with a significantly impaired ability to increase cardiac output with exercise. The lowered cardiac output with exercise results from both cardiac and peripheral causes. T2DM is associated with left ventricular (LV) diastolic dysfunction based on LV hypertrophy with myocardial disperse fibrosis and significantly impaired ability for myocardial blood flow increments with exercise. T2DM is also associated with impaired ability for skeletal muscle vasodilation during exercise, and as is the case in the myocardium, such changes may be related to vascular rarefaction. The present review discusses the underlying phenotypical changes of the heart and peripheral vascular system and their importance for an adequate increase in cardiac output. Since many of the described cardiovascular changes with T2DM must be considered difficult to change if fully developed, it is suggested that patients with T2DM are early evaluated with respect to their cardiovascular compromise.

New perspectives in the echocardiographic hemodynamics multiparametric assessment of patients with heart failure.

International Guidelines consider left ventricular ejection fraction (LVEF) as an important parameter to categorize patients with heart failure (HF) and to define recommended treatments in clinical practice. However, LVEF has some technical and clinical limitations, being derived from geometric assumptions and is unable to evaluate intrinsic myocardial function and LV filling pressure (LVFP). Moreover, it has been shown to fail to predict clinical outcome in patients with end-stage HF.The analysis of LV antegrade flow derived from pulsed-wave Doppler (stroke volume index, stroke distance, cardiac output, and cardiac index) and non-invasive evaluation of LVFP have demonstrated some advantages and prognostic implications in HF patients.Speckle tracking echocardiography (STE) is able to unmask intrinsic myocardial systolic dysfunction in HF patients, particularly in those with LV preserved EF, hence allowing analysis of LV, right ventricular and left atrial (LA) intrinsic myocardial function (global peak atrial LS, (PALS)). Global PALS has been proven a reliable index of LVFP which could fill the gaps "gray zone" in the previous Guidelines algorithm for the assessment of LV diastolic dysfunction and LVFP, being added to the latest European Association of Cardiovascular Imaging Consensus document for the use of multimodality imaging in evaluating HFpEF.The aim of this review is to highlight the importance of the hemodynamics multiparametric approach of assessing myocardial function (from LVFP to stroke volume) in patients with HF, thus overcoming the limitations of LVEF.

Association of left ventricular diastolic dysfunction with inflammatory activity, renal dysfunction, and liver-related mortality in patients with cirrhosis and ascites.

Left ventricular diastolic dysfunction (LVDD) is the predominant cardiac abnormality in cirrhosis. We investigated the association of LVDD with systemic inflammation and its impact on renal function, occurrence of hepatorenal syndrome (HRS) and survival in patients with cirrhosis and ascites. We prospectively enrolled 215 patients with cirrhosis and ascites. We evaluated the diagnosis and grading of LVDD by Doppler echocardiography, inflammatory markers, systemic hemodynamics, vasoactive factors, radioisotope-assessed renal function and blood flow, HRS development and liver-related mortality. LVDD was diagnosed in 142 (66%) patients [grade 2/3: n = 61 (43%)]. Serum lipopolysaccharide-binding protein (LBP), plasma renin activity (PRA) and glomerular filtration rate (GFR) were independently associated with the presence of grade 2/3 LVDD and the severity of diastolic dysfunction. Serum tumor necrosis factor-α, cardiac output and plasma noradrenaline were also independently associated with the presence of grade 2/3 LVDD. The diastolic function marker E/e' was strongly correlated with serum LBP (r = 0.731; P < 0.001), PRA (r = 0.714; P < 0.001) and GFR (r = -0.609; P < 0.001) among patients with LVDD. The 5-year risk of HRS development and death was significantly higher in patients with grade 2/3 LVDD compared to those with grade 1 (35.5 vs. 14.4%; P = 0.01 and 53.3 vs. 28.2%; P = 0.03, respectively). The occurrence and severity of LVDD in patients with cirrhosis and ascites is closely related to inflammatory activity. Advanced LVDD is associated with baseline circulatory and renal dysfunction, favoring HRS development, and increased mortality.

Abstract 57: Gut Microbiota, Blood Metabolites and Left Ventricular Diastolic Dysfunction in US Hispanics/Latinos

Abstract 57: Gut Microbiota, Blood Metabolites and Left Ventricular Diastolic Dysfunction in US Hispanics/Latinos

Abstract P534: Sex Differences in Left Ventricular Diastolic Function and Cognitive Performance in Midlife: Evidence From the Bogalusa Heart Study

Background: Despite the growing interest in the role of isolated left ventricular (LV) diastolic dysfunction in cardiac remodeling, little is known about its association with cognitive performance in midlife, prior to the onset of dementia. Hypothesis: We hypothesized that LV diastolic dysfunction and cardiac remodeling will be associated with cognitive performance in middle-aged adults. These associations might differ by sex and race. Aim: To investigate the impact of left atrial (LA) size, LV mass, volume, systolic and diastolic function on cognition in middle-aged Black and White, men and women from a rural, community-based cohort, the Bogalusa Heart Study (BHS), in Louisiana. Methods: A total of 1,107 participants from the BHS (48.1±5.4 years, 56.7% female, 34.3% black) with echocardiography and cognitive testing were included. Cognitive performance was quantified in a global cognitive score (GCS) comprised of the z standardized sum of 7 neuropsychiatric tests. Multivariate linear regression analysis was used for the association of E/e’, LA volume index (LAVi), LV end-diastolic volume (LVEDV), mass index (LVMi) as well as ejection fraction (LVEF) with GCS adjusted for age, sex, race, systolic and diastolic blood pressure, total and HDL cholesterol, history of smoking, diabetes, and hypertension as well as education. Interactions by sex and race were tested. Results: Even after adjusting for age, sex and race, larger LAVi, LVEDV, LVMi, higher E/e’ and lower e’ were associated with poorer cognitive function (all p &lt;0.05), but not LVEF. These associations remained significant for E/e’, e’, and LVMi after adjusting for systolic and diastolic blood pressure, total and HDL cholesterol, history of smoking, diabetes, hypertension, as well as education. There was no significant race interaction. In contrast, the association of E/e’ with GCS was significantly stronger (standardized β coefficient =-0.20; p &lt;0.01) in middle-aged women, but not in middle-aged men (standardized β coefficient =-0.04; p &lt;0.36; p interaction=0.02). Conclusion: LV diastolic function is more closely associated with mid-life cognition than systolic function, and the association is present among middle aged women but not men.

Abstract P161: Association Between Kidney Function and Pre-Heart Failure: Insights From the Echocardiographic Study of Latinos (Echo-SOL)

Background: Impaired kidney function is an independent risk factor for heart failure (HF), but its association with pre-HF is not as well studied. We assessed kidney function in relation to pre-HF in a diverse Hispanic/Latino population in the US. Methods: Echocardiographic data from visit (V) 1 and 2 of Echo-SOL were analyzed (unweighted n=1643). Prevalent pre-HF was defined as any abnormal echocardiographic parameter at V1: left ventricular (LV) systolic dysfunction (LVSD) [ejection fraction &lt;50%, global longitudinal strain &gt;15%]; LV diastolic dysfunction (LVDD) &gt;grade 1; and LV remodeling (LVR) [LV mass index &gt;115 g/m2 in men, &gt;95 g/m2 in women, relative wall thickness &gt;0.42]. Incident pre-HF was defined at V2 among those without pre-HF at V1 (unweighted n=588). Kidney function was assessed by cystatin C (per 10 mg/L), eGFR (MDRD-traditional and CKD-EPI, per 5 mL/min/1.73 m2), and urine albumin creatinine ratio (UACR, per 10 units). Survey logistic regression analyses were used to examine the association of kidney function measures with prevalent and incident pre-HF and its domains (LVSD, LVDD, LVR), unadjusted and adjusted for age and sex and accounting for the complex survey design. Results: At V1 (mean age 56 years, 55% female), 66.7% had prevalent pre-HF; at V2, 66.3% had incident pre-HF. UACR was significantly associated with prevalent pre-HF and LVR in all models (Table 1-2). Higher cystatin C was significantly associated with incident pre-HF, LVDD, and LVR in all models; whereas eGFR (CKD-EPI) showed a marginal inverse relation with prevalent and incident pre-HF, LVDD and LVR, but only remained associated with LVR in adjusted models (Table 1-2). Conclusion: Declining kidney function (higher UACR and cystatin C) is associated with prevalent and incident pre-HF, diastolic dysfunction, and cardiac remodeling. Lower eGFR is also associated with cardiac remodeling in this population. Screening for kidney function could help us identify pre-HF and start protective therapies earlier to most effectively prevent overt HF.

Prognostic Implications of Left Atrial Strain in Bicuspid Aortic Valve With Chronic Aortic Regurgitation.

Left atrial reservoir strain (LARS) is a novel imaging biomarker of left ventricular diastolic dysfunction. This study aimed to examine the prognostic implications of LARS in patients with bicuspid aortic valve and significant (moderate-severe to severe) aortic regurgitation. A total of 220 patients with bicuspid aortic valve and significant aortic regurgitation were prospectively enrolled in our study. LARS and left ventricular global longitudinal strain were derived from speckle-tracking echocardiography. The end point was a composite of all-cause mortality, heart failure hospitalization, and aortic valve repair or replacement. The threshold value of LARS <24% was used to identify impaired left atrial mechanics based on prior results. During a median follow-up of 364 (interquartile range, 294-752) days, 46 patients (20.9%) reached the composite end points. On multivariable Cox analysis, impaired LARS (adjusted hazard ratio, 2.08 [95% CI, 1.05-4.11]; P=0.036) was a statistically significant predictor of composite end points after adjustment for other statistically significant predictors. Finally, adding impaired LARS to other statistically significant predictors (New York Heart Association functional class and left ventricular global longitudinal strain) significantly improved the global χ2 (from 32.19 to 36.56; P=0.037) and reclassification (continuous net reclassification index=0.55; P<0.001) of the prediction model. In patients with bicuspid aortic valve and significant aortic regurgitation, the impairment of LARS is a strong independent prognostic predictor and confers incremental prognostic utility over clinical and other echocardiographic parameters. These findings suggest that LARS could be considered in risk stratification for such populations.

Cardio-Oncoimmunology: Cardiac Toxicity, Cardiovascular Hypersensitivity, and Kounis Syndrome.

Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even at very low medication dosages, and can present as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome, and myocarditis caused by cancer therapy.

Unattended automatic blood pressure measurements vs conventional office readings in predicting hypertension-mediated organ damage.

Hypertension is a leading cardiovascular risk factor. Accurate blood pressure (BP) measurement is pivotal in hypertension diagnosis and management. Conventional office blood pressure measurements (OBPMs) are error‑prone, exacerbated by the white‑coat effect. Unattended automated office blood pressure measurement (UAOBPM) is emerging as an alternative, mitigating the white‑coat effect. However, its ability to predict hypertension‑mediated organ damage (HMOD) remains disputable. This study compares UAOBPM with OBPM in terms of their association with various types of HMOD, including left ventricular hypertrophy, left atrial enlargement, left ventricular systolic and diastolic dysfunction, intima‑media complex thickening, microalbuminuria, and abnormal pulse wave velocity. A total of 219 hypertensive patients were recruited, interviewed, and examined. Subsequently, BP measurements were conducted in a randomized manner: 1) UAOBPM, after 5 minutes of solitary rest in an examination room, BP was automatically measured 3 times at 1‑minute intervals; 2) OBPM, after 5 minutes of rest, a physician performed 3 consecutive BP measurements at 1‑minute intervals. Subsequent evaluations aimed to detect HMOD and included echocardiography, carotid artery ultrasound, pulse wave velocity assessment, and laboratory tests. UAOBP values were lower than the OBP ones (mean [SD], 124.7 [14.4] vs 128.2 [14.2] mm Hg; P <0.001 for systolic BP, and 73.3 [10.2] vs 75.2 [10.6] mm Hg; P <0.001 for diastolic BP). Correlation and receiver operating characteristic curve analyses revealed no superiority of either method in predicting HMOD. The UAOBPM did not prove superior to OBPM in predicting HMOD. Further research is warranted to determine the role of UAOBPM in clinical practice.

Effect of sacubitril/valsartan on the hypertensive heart in continuous light-induced and lactacystin-induced pre-hypertension: Interactions with the renin-angiotensin-aldosterone system

This study investigated whether sacubitril/valsartan or valsartan are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in two experimental models of pre-hypertension induced by continuous light (24 hours/day) exposure or by chronic lactacystin treatment, and how this potential protection interferes with the renin-angiotensin-aldosterone system (RAAS). Nine groups of three-month-old male Wistar rats were treated for six weeks as follows: untreated controls (C), sacubitril/valsartan (ARNI), valsartan (Val), continuous light (24), continuous light plus sacubitril/valsartan (24+ARNI) or valsartan (24+Val), lactacystin (Lact), lactacystin plus sacubitil/valsartan (Lact+ARNI) or plus valsartan (Lact+Val). Both the 24 and Lact groups developed a mild but significant systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, as well as LV systolic and diastolic dysfunction. Yet, no changes in serum renin-angiotensin were observed either in the 24 or Lact groups, though aldosterone was increased in the Lact group compared to the controls. In both models, sacubitril/valsartan and valsartan reduced elevated SBP, LV hypertrophy and fibrosis and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan and valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1–5, Ang 1–7 in the 24 and Lact groups and reduced aldosterone in the Lact group. We conclude that both continuous light exposure and lactacystin treatment induced normal-to-low serum renin-angiotensin models of pre-hypertension, whereas aldosterone was increased in lactacystin-induced pre-hypertension. The protection by ARNI or valsartan in the hypertensive heart in either model was related to the Ang II blockade and the protective Ang 1–7, while in lactacystin-induced pre-hypertension this protection seems to be additionally related to the reduced aldosterone level.