Left Ventricular Diastolic Dysfunction Research Articles

Changes in Cardiac Structure and Function of Recipients after Kidney Transplantation.

Background: Chronic kidney disease (CKD) elevates the risk of cardiovascular disease (CVD) and mortality. Uremic cardiomyopathy, frequently observed in CKD and end-stage renal disease (ESRD), involves alterations in cardiac structure and function, which may reverse post-kidney transplantation, although data remain controversial. This study examines the relationship between graft function and changes in cardiac parameters pre- and post-transplantation in kidney transplant recipients. Methods: A total of 145 pediatric and adult recipients of living or deceased donor kidney transplants were enrolled at Gazi Yaşargil Training and Research Hospital. This cohort study utilized transthoracic echocardiographic (TTE) imaging pre-transplant and at least two years post-transplant. Echocardiographic parameters were analyzed using standard techniques. Results: The mean age of the participants was 35 years, with 60% male. The average dialysis duration prior to transplantation was 27 months. Most recipients (83.4%) received kidneys from living donors. Left ventricular diastolic dysfunction increased significantly post-transplant (p < 0.05), while other cardiac dimensions and functions, such as ejection fraction and pulmonary artery pressure, showed no significant change (p > 0.05). Notably, diastolic dysfunction worsened in patients with dysfunctional grafts (GFR < 45), correlating with increased pulmonary artery pressure post-transplant. The rate of antihypertensive drug use and the prevalence of diabetes mellitus increased significantly post-transplant (p < 0.05). Conclusions: This study demonstrates that left ventricular diastolic dysfunction present before kidney transplantation continues to persist post-transplantation in patients with end-stage renal disease undergoing chronic kidney disease treatment. Furthermore, it shows an increased rate of pulmonary artery pressure and pericardial effusion in patients with dysfunctional grafts after transplantation. Further research is required to explore strategies to reverse uremic cardiomyopathy and reduce cardiovascular risk in these patients.

Development and validation of a nomogram to predict risk of septic cardiomyopathy in the intensive care unit

The aim of this study was to develop a simple but effective nomogram to predict risk of septic cardiomyopathy (SCM) in the intensive care unit (ICU). We analyzed data from patients who were first admitted to the ICU for sepsis between 2008 and 2019 in the MIMIC-IV database, with no history of heart disease, and divided them into a training cohort and an internal validation cohort at a 7:3 ratio. SCM is defined as sepsis diagnosed in the absence of other cardiac diseases, with echocardiographic evidence of left (or right) ventricular systolic or diastolic dysfunction and a left ventricular ejection fraction (LVEF) of less than 50%. Variables were selected from the training cohort using the Least Absolute Shrinkage and Selection Operator (LASSO) regression to develop an early predictive model for septic cardiomyopathy. A nomogram was constructed using logistic regression analysis and its receiver operating characteristic (ROC) and calibration were evaluated in two cohorts. A total of 1562 patients participated in this study, with 1094 in the training cohort and 468 in the internal validation cohort. SCM occurred in 13.4% (147 individuals) in the training cohort, 16.0% (75 individuals) in the internal validation cohort. After adjusting for various confounding factors, we constructed a nomogram that includes SAPS II, Troponin T, CK-MB index, white blood cell count, and presence of atrial fibrillation. The area under the curve (AUC) for the training cohort was 0.804 (95% CI 0.764–0.844), and the Hosmer–Lemeshow test showed good calibration of the nomogram (P = 0.288). Our nomogram also exhibited good discriminative ability and calibration in the internal validation cohort. Our nomogram demonstrated good potential in identifying patients at increased risk of SCM in the ICU.

Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease.

The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes. We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD-related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short-term finerenone treatment decreased LV end-diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity. We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.

Serum bile acid profiles are associated with heart failure with preserved ejection fraction in patients with metabolic dysfunction-associated fatty liver disease: An exploratory study.

To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.

Association of high-sensitivity troponin T with left ventricular dysfunction in prediabetes

Background Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are an increasingly serious problem worldwide. Tissue Doppler imaging (TDI), a non-invasive technique, may evaluate both systolic and diastolic function during the first phases of cardiovascular disease (CVD). High-sensitivity cardiac troponin T (hs-cTnT) can detect subclinical myocardial injury in asymptomatic prediabetic patients. Aim We aimed to investigate the relationship between left ventricular (LV) function and hs-cTnT in prediabetic patients. Methods Between 1 October 2021 and 1 October 2022, we recruited 96 prediabetic and an equal number of age- and gender-matched healthy volunteers prospectively. TDI was used to evaluate both systolic and diastolic functions. Hs-cTnT levels were obtained and compared between groups. Results It was found that the values for mitral annular plane systolic excursion (MAPSE), E, the rapid filling wave, E/Em, and the peak annular velocities of systolic excursion in the ejection period (Sm) were all significantly higher in these patients compared to healthy individuals (p < .001). Hs-cTnT was an independent predictor of left ventricular diastolic dysfunction (LVDD) and left ventricular systolic dysfunction (LVSD) (odds ratio [OR] = 2.625, 95% confidence interval [CI] = 1.324–4.308, p < .001, and OR = 1.922, 95% CI = 0.454–3.206, p = .004). Conclusions Prediabetics had higher hs-cTnT levels than controls. We showed that LVSD and LVDD functions were negatively affected in prediabetic patients. Our results proved that hs-cTnT levels may be associated with subclinical LV dysfunction in prediabetes.

Sarcopenia emerges as a risk factor for cardiac diastolic dysfunction: a new focus for research

ObjectivesCardiac diastolic dysfunction (left ventricular diastolic dysfunction [LVDD]) is a well-known predictor of heart failure. We hypothesized that sarcopenia is independently associated with diastolic dysfunction. We aimed to investigate the association of the most recent consensus definition of sarcopenia with LVDD. MethodsWe included 121 older participants admitted to a cardiology outpatient clinic. We followed the European Working Group on Sarcopenia in Older People 2 definition of confirmed sarcopenia (presence of low muscle mass and low muscle strength). We estimated skeletal muscle mass with bioimpedance analysis and muscle strength by hand grip strength via a Jamar hydraulic hand dynamometer. Skeletal muscle mass was adjusted by body mass index. LVDD was determined by echocardiographic parameters measured per American Society of Echocardiography recommendations. We ran multivariate logistic regression analyses adjusted for well-known risk factors for diastolic dysfunction (i.e., age, sex, obesity, smoking, diabetes mellitus, hypertension, and ischemic heart disease) to detect whether sarcopenia was independently associated with diastolic dysfunction. We gave results in odds ratio (OR) and 95% confidence interval (CI). ResultsMean age was 69.9 ± 5.8 years, and 38.8% of participants were male. Confirmed sarcopenia was detected in 34.7%, and diastolic dysfunction was detected in 19.8%. In univariate analyses, sarcopenia was associated with diastolic dysfunction (OR, 6.7, 95% CI, 2.4–18.9). Regression analyses showed that two parameters, sarcopenia (OR, 7.4, 95% CI, 2.1–26.6, P = 0.002) and obesity (OR, 5.0, 95% CI, 1.03–24.6, P = 0.046), were associated with diastolic dysfunction. ConclusionsThis study revealed sarcopenia to be a new risk factor for diastolic dysfunction, adding to its known risk factors. Future longitudinal studies are needed to clarify the factors underlying their copresence.

Cardiac electrophysiology, structure and diastolic function in patients with diabetic foot versus those without diabetic foot.

To evaluate the differences in cardiac autonomic function, cardiac structure and diastolic function between individuals with diabetic foot (DF) and those with diabetes but without DF. A total of 413 individuals with DF and 437 without DF who underwent a 24-h electrocardiogram Holter and a Doppler echocardiogram were included. The heart rate variability parameters to evaluate cardiac autonomic function, and the indices for the assessment of cardiac structure and left ventricular (LV) diastolic function, including left atrium, LV posterior wall thickness, interventricular septum and E/e' ratio, were measured or calculated. Propensity score matching was used for the sensitivity analysis to minimize potential imbalance. In both the crude and propensity score matching analyses, significant differences were observed in heart rate variability between individuals with and without DF, as evidenced by lower standard deviation of the normal sinus interval, lower low-frequency power/high-frequency power ratio, lower standard deviation of the 5-min average RR intervals, lower low-frequency power, lower percentage of normal adjacent RR interval difference >50 ms, lower root mean square of successive RR interval differences and lower high-frequency power (all P < 0.05). In multivariate analysis, DF showed an independent negative correlation with the aforementioned indices of heart rate variability (all P < 0.05). Individuals with DF showed higher left atrium, LV posterior wall thickness, interventricular septum and a higher E/e' ratio than those without DF in the crude analysis (all P < 0.05), whereas these indices were no longer associated with DF in the multivariate analysis and the propensity score matching analyses. Cardiac autonomic modulation was more severely impaired in individuals with DF than in their counterparts without DF. There has been insufficient evidence to demonstrate the independent association of DF and LV diastolic dysfunction.

Diastolic Dysfunction of the Left and Right Ventricles in Patients with Calcium Pyrophosphate Crystal Storage Disease and Osteoarthritis.

The frequency and risk factors for the development of diastolic dysfunction (DD) in patients with CPPD and OA have not been studied. The objective of this study was to determine the frequency and identify risk factors (RF) for the development of DD of the left and right ventricles (LV and RV) in patients with calcium pyrophosphate crystal deposition disease (CPPD) and osteoarthritis (OA). The study included 26 patients with CPPD and with knee OA 18-65 years old, matched in age and gender, without cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), and rheumatic diseases. Conventional risk factors (TRF) of CVD were assessed, and echocardiography was performed. The frequency of DD in patients with CPPD and OA was quite high and almost did not differ in both groups: it was detected in 19 patients, of which 11 (42%) had CPPD and 8 (31%) had OA (p = 0.39). Type 1 LV DD was detected in 10 (39%) patients with CPPD and in 8 (31%) with OA (p = 0.11); type 1RV DD was detected in 8 (31%) patients with CPPD and in 7 (27%) patients with OA (p = 0.17); and type 1 LV DD and RV DD was detected in 7 (27%) patients with both CPPD and with OA. DD types 2 and 3 were not detected in both groups. There were no differences in both groups in CV risk factors, except for the level of CRP (it was higher in CPPD) (p = 0.03). In the CPPD group, mean values of LV E/E' (p = 0.02), LVDT (p = 0.03), LVMI (p = 0.04) were significantly higher than in patients with OA. On the contrary, in patients with OA, indices EDV (p = 0.004) and TVC (p = 0.02) were higher. There were direct correlations between diastolic function indices and the following factors in CPPD: LVL, PWLV and PTH level (r = 0.7, p <0.005), LV E' and PTH level (r = 0.7, p < 0.005). Inverse correlations were found between the level of PTH and IS (r = -0.5, p < 0.005), LVMI (r = -0.5, p < 0.005), and the level of vitamin D and VDDT (r = -0.6, p < 0.005). Direct correlations in OA were found between the level of CRP and PVAdiast (r = 0.6, p < 0.005), and the level of sUA (r = 0.7, p < 0.005), and the level of vitamin D and E/E'LV (r = 0.6, p < 0.005). A high prevalence of LV and RV DD was found in patients with CPPD and OA. The presence of DD in CPPD was associated with lower vitamin D levels, and in OA with a higher level of sUA and a lower level of PTH.

Longitudinal strain correlates with 6-minute walk distance whereas ejection fraction and diastolic parameters do not

BackgroundImpaired functional capacity is a common symptom in patients with heart failure. Standard measures of left ventricular (LV) function, such as ejection fraction (EF) and LV diastolic parameters, do not correlate with measures of functional capacity. The aim of this study is to determine if measures of global and regional LV strain better correlate with 6-minute walk distance than does EF or measures of LV diastolic function.Methods120 patients referred to a cardiology clinic for evaluation of known or suspected heart failure were approached for enrollment. Of those 120 patients, 58 had an echocardiogram within 3 months of enrollment with images adequate for regional and global strain assessment, had no contra-indication to exercise testing, and had no previously documented non-cardiac explanation for dyspnea on exertion. In those 58 patients, 6-minute walk distance was measured, LV EF was determined with Simpson’s biplane method, and global and regional longitudinal strain were measured with TomTec Image Arena 4.5.1 software.ResultsLV EF had no correlation with 6-minute walk distance (r = 0.22, p = 0.09) even when controlling for age, gender, and BMI (p = 0.07). No measures of LV diastolic function (including E velocity, Deceleration Time, e’ annular velocities, or E/e’) had a correlation with 6-minute walk distance. Multiple measures of global and regional LV longitudinal systolic function had a correlation with 6-minute walk distance. Longitudinal strain of the basal LV segments had the strongest correlation with 6-minute walk distance (r= -0.36, p = 0.005), and correlation persisted after controlling for age, gender, BMI, and systolic blood pressure (p = 0.004).ConclusionsLongitudinal strain correlates with a measure of functional capacity, but LVEF and traditional measures of LV diastolic dysfunction do not. Measures of longitudinal strain, especially in basal LV segments, will likely be an important marker of clinically relevant LV function.Graphical

A machine learning-derived risk score to predict left ventricular diastolic dysfunction from clinical cardiovascular magnetic resonance imaging.

The evaluation of left ventricular diastolic dysfunction (LVDD) by clinical cardiac magnetic resonance (CMR) remains a challenge. We aimed to train and evaluate a machine-learning (ML) algorithm for the assessment of LVDD by clinical CMR variables and to investigate its prognostic value for predicting hospitalized heart failure and all-cause mortality. LVDD was characterized by echocardiography following the ASE guidelines. Eight demographic and nineteen common clinical CMR variables including delayed enhancement were used to train Random Forest models with a Bayesian optimizer. The model was evaluated using bootstrap and five-fold cross-validation. Area under the ROC curve (AUC) was utilized to evaluate the model performance. An ML risk score was used to stratify the risk of heart failure hospitalization and all-cause mortality. A total of 606 consecutive patients underwent CMR and echocardiography within 7 days for cardiovascular disease evaluation. LVDD was present in 303 subjects by echocardiography. The performance of the ML algorithm was good using the CMR variables alone with an AUC of 0.868 (95% CI: 0.811-0.917), which was improved by combining with demographic data yielding an AUC 0.895 (95% CI: 0.845-0.939). The algorithm performed well in an independent validation cohort with AUC 0.810 (0.731-0.874). Subjects with higher ML scores (>0.4121) were associated with increased adjusted hazard ratio for a composite outcome than subjects with lower ML scores (1.72, 95% confidence interval 1.09-2.71). An ML algorithm using variables derived from clinical CMR is effective in identifying patients with LVDD and providing prognostication for adverse clinical outcomes.

Elevated pulmonary capillary wedge pressure, higher blood pressure, and lower cardiac index in infants with bronchopulmonary dysplasia

BackgroundLeft ventricular diastolic dysfunction indicated by elevated pulmonary capillary wedge pressure (ePCWP) may worsen cardiorespiratory status in bronchopulmonary dysplasia (BPD), but the scope of ePCWP by cardiac catheterization is not well described. MethodsThis single-center retrospective cohort study included infants with BPD without congenital heart disease, significant intracardiac shunts, or pulmonary vein stenosis who underwent cardiac catheterization from 2010 to 2021. ePCWP was defined as >10 mmHg. Quantitative measures of ventricular systolic and diastolic function were performed on existing echocardiograms. Patients with and without ePCWP were compared using the Chi-squared or Wilcoxon rank-sum tests. Associations between catheterization hemodynamics and echocardiographic parameters were assessed by simple linear regression. ResultsSeventy-one infants (93% Grade 2 or 3 BPD) met inclusion criteria, and 30 (42%) had ePCWP. Patients with ePCWP were older at catheterization (6.7 vs. 4.5 months, p < 0.001), more commonly underwent tracheostomy (66.7% vs. 29.3%, p = 0.003), and had higher mean systemic blood pressure [64.5 (56.0, 75.0) vs. 47.0 (43.0, 55.0) mm Hg, p < 0.001], higher systemic vascular resistance [11.9 (10.4, 15.6) vs. 8.7 (6.7, 11.2) WU*m2, p < 0.001), and lower cardiac index [3.9 (3.8, 4.9) vs. 4.7 (4.0, 6.3) L/min/m2, p = 0.03] at catheterization. Mean pulmonary artery pressure, pulmonary vascular resistance, and mortality were similar between the groups. Echocardiographic indices of left ventricular diastolic dysfunction did not correlate with PCWP. ConclusionsePCWP was common in infants with severe BPD who underwent cardiac catheterization in this cohort. The association between ePCWP and higher systemic blood pressure supports further study of afterload reduction in this population.

Left atrial strain in neonates with congenital diaphragmatic hernia and length of stay in pediatric intensive care unit.

The role of cardiac left ventricle (LV) dysfunction in children with congenital diaphragmatic hernia (CDH) has gained increasing attention. The hernia allows abdominal mass to enter thorax and subsequently both dislocating and compressing the heart. The pressure on vessels and myocardium alters blood flow and may interfere with normal development of the LV. A dysfunctional LV is concerning and impacts the complex pathophysiology of CDH. Hence, assessing both the systolic and diastolic LV function in the newborn with CDH is important, and it may add value for medical treatment and prognostic factors as length of stay (LOS) in pediatric intensive care unit (PICU). LV strain is considered an early marker of systolic dysfunction used in the pediatric population. Left atrial (LA) strain is an echocardiographic marker of LV diastolic dysfunction used in the adult population. When filling pressure of the LV increases, the strain of the atrial wall is decreased. We hypothesized that reduced LA strain and LV strain are correlated with the LOS in the PICU of newborns with CDH. This retrospective observational cohort study included data of 55 children born with CDH between 2018 and 2020 and treated at Karolinska University Hospital, Sweden. Overall, 46 parents provided consent. Echocardiograms were performed in 35 children <72 h after birth. The LA reservoir strain (LASr), LV global longitudinal strain, LV dimensions, and direction of blood flow through the patent foramen ovale (PFO) were retrospectively assessed using the echocardiograms. Children with LASr <33% (n = 27) had longer stays in the PICU than children with LA strain ≥33% (n = 8) (mean: 20.8 vs. 8.6 days; p < 0.002). The LASr was correlated with the LOS in the PICU (correlation coefficient: -0.378; p = 0.025). The LV dimension was correlated with the LOS (correlation coefficient: -0.546; p = 0.01). However, LV strain was not correlated to LOS. Newborns with CDH and a lower LASr (<33%) had longer stays in the PICU than children with LASr ≥33%. LASr is a feasible echocardiographic marker of diastolic LV dysfunction in newborns with CDH and may indicate the severity of the condition.

Evaluating Diastolic Dysfunction as an Indicator of Cirrhotic Cardiomyopathy in Decompensated Chronic Liver Disease.

The clinical syndrome of cirrhotic cardiomyopathy (CCM) occurs quite frequently in decompensated chronic liver disease (DCLD) patients without any prior incidence. The compromised life expectancy under such conditions was the key that prompted us to conduct this study. This study was planned to study the prevalence of diastolic dysfunction in chronic liver disease patients, to understand the diagnostic criteria of left ventricular diastolic dysfunction(LVDD) in cirrhotic patients, and to evaluate its occurrence as an early indicator of CCM. A hospital-based, cross-sectional study was conducted on 158 patients, admitted to the Department of Medicine, Rajendra Institute of Medical Sciences, Ranchi, India, who conformed to our criteria for inclusion and exclusion.The study period was for 18 months. The subjects were clinically and radiologically diagnosed with chronic liver disease. Regression analysis for variables was performed to score the effects of potential variables with outcomes for diastolic dysfunction (DD) prediction. Out of 158 patients, 116 belonged to the age group of 31-60 years, pronouncing age to be a significant factor for LVDD. Fifty-threesubjects had serum bilirubin levels >2mg/dL and we found serum bilirubin levels to bear a significant correlation with LVDD by exhibiting a p-value <0.0001. Both the Child-Turcotte-Pugh score class (p-value=0.0180) and QTc (p-value <0.0001) bear significant correlation with the development of LVDD, which is also evident from their area under the curve (AUC) values of 0.64 in the receiver operating characteristic (ROC) curve. Our study concludes that LVDD is an early indicator for assessing the severity of liver cirrhosis in DCLD. The correlation of DCLD with prolonged QTc could predispose patients with DCLD to ventricular arrhythmias. Hence, such patients should undergo serum bilirubin tests, and electrocardiographic checks at regular intervals for early detection, to increase their overall survival rates.

Left Atrial Peak Systolic Strain as an Indicator Pathway of Diastolic Dysfunction of the Left Ventricle.

Left atrial peak systolic strain (LA-PSS) imaging is an emerging index of left atrial function, and it was shown to be decreased in heart failure with preserved ejection fraction (EF). We aimed to determine whether LA-PSS could be used as an additional diagnostic parameter to current existing guidelines for the presence of left ventricle diastolic dysfunction (LVDD). A total of 190 consecutive adult patients with cardiovascular risk factors and normal left ventricle EF with no prior history of heart failure were included in the study. Speckle tracking software was used to study ventricular parietal deformity, left ventricle global longitudinal systolic strain, and LA-PSS. The median left ventricle global longitudinal systolic strain was -19%, with a significant difference ( P < 0.001) between patients with normal diastolic function versus those with LVDD. The median LA-PSS was 33% (30% to 38%) ( P < 0.001). Most patients (61%) had grade 1 atrial dysfunction based on PSS (range 24%-35%). The analysis of the area under the receiver operating characteristic curve of the LA-PSS as a potential indicator pathway of LVDD was 67% [95% confidence interval (CI), 62-72], and 75% (95% CI, 70-80), when the indeterminate pattern was included. The decreased LA-PSS made it possible to reclassify patients with an indeterminate pattern of diastolic function in 96% of cases. These results support the potential role of LA-PSS as an additional parameter for the diagnosis of LVDD in patients with normal EF, and may be integrated into the guidelines for routine evaluation of patients.

The total xanthones extracted from Gentianella acuta alleviates HFpEF by activating the IRE1α/Xbp1s pathway

AbstractHeart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by pulmonary and systemic congestion resulting from left ventricular diastolic dysfunction and increased filling pressure. Currently, however, there is no evidence on effective pharmacotherapy for HFpEF. In this study, we aimed to investigate the therapeutic effect of total xanthones extracted from Gentianella acuta (TXG) on HFpEF by establishing an high‐fat diet (HFD) + L‐NAME‐induced mouse model. Echocardiography was employed to assess the impact of TXG on the cardiac function in HFpEF mice. Haematoxylin and eosin staining, wheat germ agglutinin staining, and Masson's trichrome staining were utilized to observe the histopathological changes following TXG treatment. The results demonstrated that TXG alleviated HFpEF by reducing the expressions of genes associated with myocardial hypertrophy, fibrosis and apoptosis. Furthermore, TXG improved cardiomyocyte apoptosis by inhibiting the expression of apoptosis‐related proteins. Mechanistic investigations revealed that TXG could activate the inositol‐requiring enzyme 1α (IRE1α)/X‐box‐binding protein 1 (Xbp1s) signalling pathway, but the knockdown of IRE1α using the IRE1α inhibitor STF083010 or siRNA‐IRE1α impaired the ability of TXG to ameliorate cardiac remodelling in HFpEF models. In conclusion, TXG alleviates myocardial hypertrophy, fibrosis and apoptosis through the activation of the IRE1α/Xbp1s signalling pathway, suggesting its potential beneficial effects on HFpEF patients.

Chronic dioxin exposure aggravates endothelial damage and left ventricular diastolic dysfunction only in male obese mice

Chronic dioxin exposure aggravates endothelial damage and left ventricular diastolic dysfunction only in male obese mice

Left Atrioventricular Coupling Index: A Novel Diastolic Parameter to Refine Prognosis in Heart Failure

Left atrioventricular coupling index (LACI), an index coupling left atrial to left ventricular (LV) volume at end-diastole, has been shown to be associated with prognosis in different clinical settings. However, the relation between LACI and LV diastolic dysfunction (DD) remains to be established. The aims of the present study were to investigate the association between LACI and LV DD and to assess its prognostic value in patients with heart failure (HF). A total of 1,158 patients with HF in stable condition, on optimal medical therapy, were retrospectively analyzed (derivation cohort). Clinical and echocardiographic features were characterized across LACI tertiles. The independent prognostic value of LACI (end point: all-cause death or HF hospitalization) was assessed using Cox regression. Results were validated in an external cohort of 242 patients with HF. In the derivation cohort, the median LACI value was 0.29 (interquartile range, 0.19-0.42). Patients in the third tertile (LACI>0.36) were older and presented with more advanced HF symptoms. Although the prevalence of grade 1 DD (American Society of Echocardiography/European Association of Cardiovascular Imaging classification) progressively decreased across LACI tertiles, the prevalence of grade 3 DD significantly increased (8%, 23%, and 46%, respectively; P<.0001). A cutoff value of ≥0.26 identified moderate to severe DD with an area under the curve of 0.75. During follow-up (median, 28months; interquartile range, 11-53 months), 407 patients (35%) reached the end point. On multivariable analysis, LACI was independently associated with outcomes (hazard ratio for a 1-SD increase, 1.16; 95% CI, 1.06-1.28; P=.002), showing incremental predictive value over the DD grading system (net reclassification improvement=0.150, P<.0001). The prognostic value of LACI was consistent in the external validation cohort. LACI is associated with DD severity and is an independent predictor of outcomes in patients with HF.

Non-cardiac comorbidities in heart failure: an update on diagnostic and management strategies.

Managing non-cardiac comorbidities in heart failure (HF) requires a tailored approach that addresses each patient's specific conditions and needs. Regular communication and coordination among healthcare providers is crucial to providing the best possible care for these patients. Poorly controlled hypertension contributes to left ventricular remodeling and diastolic dysfunction, emphasizing the importance of optimal blood pressure control while avoiding adverse effects. Among HF patients with diabetes, SGLT2 inhibitors and mineralocorticoid receptor antagonists have shown promise in reducing HF-related morbidity and mortality. Chronic kidney disease exacerbates HF and vice versa, forming the vicious cardiorenal syndrome, so disease-modifying therapies should be maintained in HF patients with comorbid CKD, even with transient changes in kidney function. Anemia in HF patients may be multifactorial, and there is growing evidence for the benefit of intravenous iron supplementation in HF patients with iron deficiency with or without anemia. Obesity, although a risk factor for HF, paradoxically offers a better prognosis once HF is established, though developing treatment strategies may improve symptoms and cardiac performance. In HF patients with stroke and atrial fibrillation, anticoagulation therapy is recommended. Among HF patients with sleep-disordered breathing, continuous positive airway pressure may improve sleep quality. Chronic obstructive pulmonary disease often coexists with HF, and many patients can tolerate cardioselective beta-blockers. Cancer patients with comorbid HF require careful consideration of cardiotoxicity risks associated with cancer therapies. Depression is underdiagnosed in HF patients and significantly impacts prognosis. Cognitive impairment is prevalent in HF patients and impacts their self-care and overall quality of life.

Comparing Left Ventricular Structure and Functions in End-Stage Renal Disease Using Conventional Echocardiography and 2D Speckle Tracking Echocardiography.

Patients on hemodialysis (HD) are prone to various cardiovascular complications. Two-dimensional speckle tracking echocardiography (2D STE) is an innovative technique for early myocardial dysfunction detection, even with normal ejection fraction (EF). We aim to detect left ventricle (LV) dysfunction in regular hemodialysis patients using 2D STE compared to traditional echocardiography. The study comprised 30 patients with end-stage renal disease (ESRD), subdivided according to left ventricular mass index (LVMI) into group 1 with left ventricular hypertrophy (LVH) (n=19) and group 2 without LVH (n=11). Another 30 healthy control subjects were recruited as group 3. The EF, average systolic velocity (Sa), and 2D LV strain were taken as measures of LV systolic function. The indicators for diastolic function included the E/A ratio and E velocity/peak early diastolic velocity. Regarding the parameters of LV systolic and diastolic functions assessed by traditional echocardiography, we found no significant difference between groups 1 and 2. However, using 2D STE, we observed significant differences in the average Sa velocity (p=0.025), average LV strain (p=0.03), 2D global longitudinal strain (GLS) (p=0.03), E/Ea (p=0.003), and LV myocardial performance index (MPI) (p=0.006). Also, a significant positive correlation was found between LVMI and left ventricular end-diastolic diameter (LVEDD) (p<0.01, r=0.63), EF measured by 2D (p=0.034, r=0.39), mitral E/A ratio (p=0.03, r=0.49), and mitral E/Ea (p<0.01, r=0.72). There was a significantly strong negative correlation between LVMI and 2D average LV strain (p=0.034, r=-0.39). We concluded that 2D STE is more sensitive than a conventional echo in detecting early LV systolic and diastolic dysfunction even in patients with normal EF.

Impaired cardiac mitochondrial bioenergetics contribute to loss of cardiac function, in a porcine multiple risk factor model

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch CardioVascular Alliance (an initiative with support of the Dutch Heart Foundation) Grant 2020B008 RECONNEXT, and the German Center for Cardiovascular Research (DZHK; 81Z0600207) Background Heart failure with preserved ejection fraction lacks targeted therapies, due to insufficient understanding of pathogenesis. A multiple comorbidity swine model (MCS) was developed by exposure to three risk factors for six months including diabetes (streptozotocin), chronic kidney disease (renal embolization), and an unhealthy diet (high-fat, high salt diet). An additional risk factor ovariectomy was added on top of the MCS model (MCS+). MCS and MCS+ presented with left ventricular diastolic dysfunction, oxidative stress, coronary microvascular dysfunction and inflammation. Furthermore, myocardial oxygen consumption was increased given the same level of cardiac work (Fig. A), suggesting an impairment in myocardial mitochondrial function. Using a combined-omics approach, the purpose of this study is to unravel alterations in gene expression and proteome abundance regarding mitochondrial function in MCS swine. Methods 15 MCS, 4 MCS+ and 10 healthy control female swine were included in the study. Proteome analysis and single nuclei RNA sequencing, were performed on frozen MCS left ventricle myocardial samples. Cardiac mitochondrial function was measured by an O2k-FlouRespirometer ex vivo in MCS+ swine versus control. Results Proteome analysis showed a reduced abundance of proteins involved in branched-chain amino acid (BCAA) catabolism (Fig. B). Single nuclei RNA sequencing of a subgroup of the same animals demonstrated a downregulation of these genes specifically in cardiomyocyte subpopulations. BCAA can act as a source of ATP via oxidative phosphorylation and can modulate mitochondrial substrate utilisation, and impair mitochondrial function, resulting in increased mitochondrial production of reactive oxygen species (ROS). Mitochondrial function was measured in fresh myocardial tissue, using pyruvate/malate/glutamate as substrate. Low mitochondrial respiratory sensitivity to ADP was observed 26±2.5 in MCS+ vs 43.6±1.5 pmol/(s*mg tissue) in healthy control, reflecting low oxidative capacity. Moreover, the respiratory rate after uncoupling by FCCP was reduced in MCS+ versus healthy control (73.6±11.7 vs 118.4±15.6 pmol/(s*mg tissue). These findings are consistent with our data in the MCS swine and indicate impaired BCAA in the myocardium of animals with comorbidities, which is associated with increased ROS levels (8-isoprostane 12.9±0.8 pg/mg protein in MCS vs 10.3±0.5 in healthy animals) and impaired myocardial efficiency during exercise (Fig. A). Conclusion A combined omics approach suggested an alteration in cardiac mitochondria. Respiratory analyses showed impaired mitochondrial bioenergetics and increased oxidative stress, which can contribute to diastolic dysfunction.