Left Ventricular Diastolic Dysfunction Research Articles

Energy wavelet signal processed ECG and standard 12 lead ECG: Diagnosis of early diastolic dysfunction.

Left ventricular (LV) diastolic dysfunction (LVDD) is the result of impaired LV relaxation and identifies those at risk of developing heart failure. Echocardiography has been used as the gold standard to identify early LVDD. The signal processed electrocardiogram (hsECG) has demonstrated effectiveness to detect early LVDD. Whether or not the standard 12‑lead electrocardiogram (ECG) can accurately predict early LVDD is not known. A standard 12‑lead ECG including signal processing (hsECG) was performed in 569 patients. Patients with atrial fibrillation, bundle branch block, pre-excitation, left ventricular hypertrophy or known cardiovascular disease were excluded, leaving 464 examinations for analysis. Early LVDD was diagnosed by established methods using echocardiography. Repolarization abnormalities (T wave discordance) in V1, V6, I and aVL and the hsECG were compared to the echocardiographic findings to establish diagnostic accuracy. A total of 84 (18.1%) patients were diagnosed with early LVDD. A combination of a borderline or abnormal finding on the hsECG produced the best diagnostic model (sensitivity 84.5%, specificity 47.9%). The best performing ECG lead was V1 with a sensitivity of 38.1% and specificity of 92.1%. Regression analysis demonstrated increasing age and V1 to be predictive of LVDD. The hsECG displayed reasonable ability to detect early LVDD. Other than V1, repolarization abnormalities on the standard 12‑lead ECG did not. While lead V1 showed promise in detecting LVDD, whether this or any other simple ECG variable can predict future LVDD would be of further interest.

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.

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

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 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.

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.

Factors associated with risk analysis for asymptomatic left ventricular diastolic dysfunction in nondialysis patients with chronic kidney disease

Heart failure (HF) constitutes a major determinant of outcome in chronic kidney disease (CKD) patients. The main pattern of HF in CKD patients is preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD) is a frequent pathophysiological mechanism and specific preclinical manifestation of HFpEF. Therefore, exploring and intervention of the factors associated with risk for LVDD is of great importance in reducing the morbidity and mortality of cardiovascular disease (CVD) complications in CKD patients. We designed this retrospective cross-sectional study to collect clinical and echocardiographic data from 339 nondialysis CKD patients without obvious symptoms of HF to analyze the proportion of asymptomatic left ventricular diastolic dysfunction (ALVDD) and its related factors associated with risk by multivariate logistic regression analysis. Among the 339 nondialysis CKD patients, 92.04% had ALVDD. With the progression of CKD stage, the proportion of ALVDD gradually increased. The multivariate logistic regression analysis revealed that increased age (OR 1.237; 95% confidence interval (CI) 1.108–1.381, per year), diabetic nephropathy (DN) and hypertensive nephropathy (HTN) (OR 25.000; 95% CI 1.355–48.645, DN and HTN vs chronic interstitial nephritis), progression of CKD stage (OR 2.785; 95% CI 1.228–6.315, per stage), increased mean arterial pressure (OR 1.154; 95% CI 1.051–1.268, per mmHg), increased urinary protein (OR 2.825; 95% CI 1.484–5.405, per g/24 h), and low blood calcium (OR 0.072; 95% CI 0.006–0.859, per mmol/L) were factors associated with risk for ALVDD in nondialysis CKD patients after adjusting for other confounding factors. Therefore, dynamic monitoring of these factors associated with risk, timely diagnosis and treatment of ALVDD can delay the progression to symptomatic HF, which is of great importance for reducing CVD mortality, and improving the prognosis and quality of life in CKD patients.

The role of atrial pacing site in reducing filling pressures by accelerated pacing in virtual HFpEF patients

Abstract Background Patients with heart failure with preserved ejection fraction (HFpEF) and pacemakers have been shown to benefit from moderately accelerated pacing rates compared to the standard 60bpm. HFpEF patients often present with prolonged P-wave duration (PWD) and atrial fibrillation. Right atrial appendage pacing (RAAP) lengthens PWD, RA septal (RASP) has a neutral effect, while Bachmann’s bundle pacing (BBP) normalizes or shortens PWD compared to sinus rhythm. The mechanical and hemodynamic effects of atrial pacing site selection remain unknown. Aim To investigate the impact of RAAP, RASP and BBP on cardiac mechanics and hemodynamics in an established cohort of virtual HFpEF patients undergoing accelerated pacing. Method HFpEF with prolonged PWD was simulated using the validated CircAdapt computational model of the human cardiovascular system. First, left ventricular (LV) diastolic dysfunction was simulated by decreasing LV myocardial relaxation rate and compliance, such that mean left atrial (LA) pressure (mLAP) was 15mmHg. Second, PWD was prolonged by prescribing a gradual electrical activation delay from RA to LA of 140ms. We then simulated atrial pacing with three different lead positions (Fig.1, left) and gradually increased pacing rate with a constant 120-ms paced atrioventricular (AV) delay. The CircAdapt model computed regional LA strain and mLAP with RAAP, RASP, and BBP. Cardiac output (5L/min) and mean arterial pressure (92mmHg) were kept constant in all simulations. Results Simulated BBP demonstrated the most synchronous LA mechanical activation and function, characterized by uniform segmental LA strain patterns and highest LA reservoir strain (LASR) (Fig.1, middle, with colored arrows highlighting the mechanical dyssynchrony). Hemodynamically (Fig.1, right), BBP acutely decreased mLAP (-1.0mmHg) at the initial heart rate of 60bpm, while RAAP increased it (+0.3mmHg). As pacing rate accelerated, BBP reduces filling pressure (mLAP: -2.8mmHg), more than RASP (-1.8mmHg) or RAAP (-1.2mmHg) at 80bpm. At high pacing rates, RASP and RAAP adversely increase mLAP, due to the prolonged atrial contraction duration and shorter LV filling time. Conclusion Our simulations of different atrial pacing sites in virtual HFpEF patients suggest that BBP yields the most synchronous LA activation pattern and a more substantial reduction in filling pressures with accelerated atrial pacing compared to RASP. Reduction in mLAP with accelerated pacing was attenuated with RAAP. While our study concentrated on a specific paced AV interval, the favorable outcomes observed with BBP could be further improved by including different, rate-adaptive, AV protocols.Fig 1.

Can CT measured LA diameter predict the presence and the degree of LV Diastolic Dysfunction?

This study was conducted to determine whether the presence and the degree of left ventricular diastolic dysfunction (LVDD) can be predicted by the simple LA diameter measured on computed tomography (CTLAD). Among adult patients who underwent both chest CT and echocardiography in the emergency department from January 2020 to December 2021, a retrospective cross-sectional study was conducted on patients in whom the time interval between the two tests was less than 24 hours. Receiver operating characteristic curve analysis was used to evaluate the diagnostic power of CTLAD for echocardiographic LVDD. In a study involving 373 patients, 192 (51.5%) had LVDD. Among them, 122 (63.5%) had grade 1, 61 (31.8%) had grade 2, and 9 (4.7%) had ≥grade 3 LVDD. Median CTLAD values were 4.1cm for grade 1, 4.5cm for grade 2, and 4.9cm for ≥grade 3 LVDD. The AUC value of CTLAD in distinguishing LVDD of ≥grade 1, ≥grade 2 (optimal cutoff ≥4.4cm), and ≥grade 3 (optimal cutoff ≥4.5cm) were 0.588, 0.657 (with sensitivity 61.4%, specificity 66.0%, positive predictive value [PPV] 29.5%, negative predictive value [NPV] 88.1%, odds ratio [OR] 3.1), and 0.834 (with sensitivity 88.9%, specificity 70.1%, PPV 6.8%, NPV 99.6%, OR 18.7), respectively. CTLAD ≥4.4cm can be used as a rough reference value to distinguish LVDD of ≥grade 2, and CTLAD ≥4.5cm can be very reliably distinguish LVDD of ≥grade 3. CTLAD might be very useful parameter in predicting LVDD in environments where echocardiography is not available.

Echocardiographic Detection of Subclinical Left Ventricular Dysfunction in Asymptomatic Type Two Diabetes Mellitus

Background: Before systolic dysfunction and symptomatic heart, diabetic cardiomyopathy begins with left ventricular diastolic dysfunction (LVDD). Echocardiographic modalities were used to detect subclinical LV impairment in asymptomatic type 2 diabetics. This study aimed to identify subclinical left ventricular impairment in asymptomatic patients with type two diabetes using several echocardiographic techniques. Methods: In the present prospective cohort study, 30 adults over 18 having type II diabetes mellitus (DM) (Group I) and 20 normal controls (Group II) were studied. Transthoracic echocardiography and 12-lead ECG were performed on all individuals. Results: Pulsed wave Doppler techniques revealed significant variation in transmitral flow velocities between groups, including septal e', lateral mitral annulus early velocity (e'), septal early diastolic peak flow velocity (E)\e', Lateral E\e', and average E\e'. EF was significantly decreased in group I (P &lt; 0.001). With a p-value of 0.001, LVESD was significantly higher in group I. The septal, lateral, and average systolic mitral annulus (S') motions in group II were significantly larger than those in group I. When comparing groups, I and II, the first showed much longer myocardial performance index (MPI) and isovolumetric contraction time (IVCT). The ET for Group I was significantly lower than that of Group II. The study group exhibited significantly greater levels of fasting blood sugar, post-prandial blood sugar, and haemoglobin A1C (HBA1C) compared to the control group (P &lt;0.001). Conclusions: Patients having diabetes mellitus exhibited considerably greater levels of DM history fasting glucose levels, postprandial glucose levels, haemoglobin A1C (HBA1C), E/e´ ratio, LVESD, IVCT, and MPI, while having significantly lower EF and ET relative to the healthy group.

H2FPEF Scores Are Increased in Patients with NASH Cirrhosis and Are Associated with Post-liver Transplant Heart Failure.

Patients with cirrhosis are at risk for cardiac complications such as heart failure, particularly heart failure with preserved ejection fraction (HFpEF) due to left ventricular diastolic dysfunction (LVDD). The H2FPEF score is a predictive model used to identify patients with HFpEF. Our primary aim was to assess the H2FPEF score in patients with cirrhosis and determine its potential to identify patients at risk for heart failure after liver transplant. This was a cohort study of patients undergoing liver transplant for cirrhosis from January 2010 and October 2018 who had a pre-transplant transthoracic echocardiogram. 166 cirrhosis subjects were included in the study. The majority were men (65%) and Caucasian (85%); NASH was the most common cause of cirrhosis (41%) followed by alcohol (34%). The median H2FPEF score was 2.0 (1.0-4.0). Patients with NASH cirrhosis had higher H2FPEF scores (3.22, 2.79-3.64) than those with alcohol induced cirrhosis (1.89, 1.5-2.29, p < 0.001) and other causes of cirrhosis (1.73, 1.28-2.18, p < 0.001). All subjects with a H2FPEF score > 6 had NASH cirrhosis. There was no association between the H2FPEF scores and measures of severity of liver disease (bilirubin, INR, or MELD score). Patients with heart failure after liver transplant had higher H2FPEF scores than those without heart failure (4.0, 3.1-4.9 vs. 2.3, 2.1-2.6, respectively; p = 0.015), but the score did not predict post-transplant mortality. H2FPEF scores are higher in cirrhosis patients with NASH and appear to be associated with post-transplant heart failure, but not death.

#2167 Polyclonal immunoglobulin free light chains: an evidence of cardiac remodeling in patients with glomerular diseases

Abstract Background and Aims It was previously shown, that polyclonal immunoglobulin free light chains (FLC) are the independent predictor of mortality in patients with decompensated heart failure, chronic kidney disease (CKD) and also in general population. Mechanisms of this phenomenon are still unknown. The aim of our study is to reveal the possible relationships between FLC and cardiac remodeling in patients with glomerular diseases. Method We included 97 patients with biopsy-proven diagnosis of different immune-mediated glomerular diseases, 53% were men, mean age was 48 ± 14.6 years. Serum Freelite FLC levels were measured as well as standard clinical and laboratory investigation. At the time of biopsy transthoracic echocardiography was also performed. Glomerular filtration rate (eGFR) was estimated by “2021 CKD-EPI Creatinine” equation. Results Median of eGFR was 46.8 ml/min/1.73 m² (28.7-80.0), FLC-kappa level was 27.4 mg/l (16.8- 48.4), FLC-lambda level was 28.2 mg/l (20.8-43.3). FLC-kappa levels were above reference range in 65%, FLC-lambda levels – in 54%. LV diastolic dysfunction (DD) was present in 68%. Comparison in groups showed that the elevation of FLC-kappa more than 19.4 mg/l was associated with bigger LV mass index (LVMI) – 138.3 ± 30.2 g/m² vs 99.9 ± 31.2 g/m² р = 0.022, the parallel correlation was found between LVMI and levels of FLC-lambda higher than 26.3 mg/l (136.2 ± 64.8 g/m² vs 104.0 ± 36.6 g/m², р = 0.023). Spearman analysis has shown statistically significant correlations between FLC levels and E/e’- Rs = 0.501 p = 0.0001 for FLC-kappa, Rs = 0.343 p = 0.012 for FLC-lambda. Combined FLC level higher than 52.9 mg/l was a significant predictor of DD with area under the ROC curve (AUC) 0.703 (sensitivity 76.5%, specificity 62.5%). Conclusion Elevation of serum pFLC level could be a promising marker of cardiac remodeling, especially, of DD in patients with glomerular diseases. Possible pathogenic role of FLC in cardiorenal relationships may be revealed in further studies.

#2406 Echocardiographic characteristics of autosomal dominant polycystic kidney disease

Abstract Background and Aims Cardiovascular complications in patients with autosomal dominant polycystic kidney disease (ADPKD) are one of the most frequently investigated extrarenal manifestations. The results are many times contradictory. This is caused by a limited size of studied populations and high inter- and intrafamilial heterogeneity of ADPKD. Expanding knowledge of populations of patients from different regions and cohorts is crucial for improving the understanding and treatment of cardiovascular morbidity and mortality. This study aims to explore the prevalence of cardiovascular abnormalities in echocardiography and to analyze their relationships with clinical characteristics across different stages of CKD progression in patients with ADPKD. Method Sixty-eight patients were included in the study. All patients underwent transthoracic echocardiography with the use of GE Vingmed Ultrasound (GE Norway Health Tech, Oslo, Norway). Information about demography, prior medical history and taking antihypertension drugs was recorded. The results of creatinine, lipids and haemoglobin were collected. To diagnose the rapid progression of CKD, creatinine was sampled twice, in a one-year interval. Results Using different indicators of left ventricular hypertrophy (LVH), we found it in above 40% of ADPKD patients. A single associate of left ventricular mass was eGFR decline after one year of observation. Other highly prevalent findings were asymptomatic left ventricular diastolic dysfunction (ALVDD) (39%), left atrium (LA) enlargement (39%) and mild valvular regurgitations (80%). Ejection fraction, aortic root dimension, tricuspid annular plane systolic excursion (TAPSE) and prevalence of mitral valve prolapse were not importantly increased. Apart from age, the strong determinant of ALVDD diagnosis was the treatment with beta-blockers. Cardiac indices were not different across the eGFR stages. Conclusion LVH, LA enlargement, ALVDD and valvular regurgitations are characteristics of cardiac phenotype in ADPKD. Cardiac indices were not different across different stages of CKD pointing towards the diagnosis of ADPKD being main drive of their occurrence.

#1431 Risk factors of adverse cardiovascular events in the early postoperative period in kidney transplant recipients

Abstract Background and Aims Kidney transplantation improves quality of life and increases life expectancy in patients with Stage 5 Chronic Kidney Disease. However, the frequency of adverse cardiovascular events in the postoperative period remains high and reduces the effectiveness of transplantation. The aim was to study the incidence of cardiovascular risk factors in the preoperative period in kidney transplant recipients with adverse cardiovascular events in the early postoperative period. Method The study included 51 kidney transplant recipients whose age was 46.1 ± 4.6 years. 12 (23.5%) recipients had adverse cardiovascular events (acute myocardial infarction, unstable angina, rhythm disturbance, complicated hypertensive crisis) in the early postoperative period. 39 (76.5%) recipients with uncomplicated postoperative period formed the comparison group. The study groups were comparable by gender and age. Results Traditional cardiovascular risk factors were assessed. The study groups had comparable rates of arterial hypertension, obesity, hyperglycemia, dyslipidemia and smoking in the preoperative period and graft function in the postoperative period. The study groups didn't have significant differences in the incidence of anemia and hemoglobin blood concentration. But the erythropoietin blood level in the preoperative period in recipients with adverse cardiovascular events was higher—38.5 (23.5-155.0) mU/mL versus 16.0 (10.0-32.0) mU/mL, p &amp;lt; 0.01, and hypererythropoietinemia was diagnosed more often—58.3% (n = 7) versus 25.6% (n = 10), p &amp;lt; 0.05, than in patients without cardiovascular events. The incidence of elevated interleukin-6 blood level in the preoperative period was higher in recipients with adverse cardiovascular events—25.0% (n = 3) versus 5.1% (n = 2), p &amp;lt; 0.05. At the same time C-reactive protein levels and white blood cell counts were not significantly different. Recipients with adverse cardiovascular events had a lower left ventricular ejection fraction—59.5 ± 10.6% versus 65.6 ± 7.1%, p &amp;lt; 0.05, and a higher incidence of left ventricular diastolic dysfunction in the preoperative period—75.0% (n = 9) versus 35.9% (n = 14), p &amp;lt; 0.05, than in recipients without cardiovascular complications. Conclusion Kidney transplant recipients with adverse cardiovascular events in the early postoperative period had a higher incidence of left ventricular diastolic dysfunction, increased blood levels of erythropoietin and interleukin-6 and a lower left ventricular ejection fraction before transplantation than recipients with an uncomplicated postoperative period.

CMR provides comparable measurements of diastolic function as echocardiography

Clinical application of cardiac magnetic resonance (CMR) is expanding but CMR assessment of LV diastolic function is still being validated. The purpose of this study was to validate assessments of left ventricular (LV) diastolic dysfunction (DD) using CMR by comparing with transthoracic echocardiography (TTE) performed on the same day. Patients with suspected or diagnosed cardiomyopathy (n = 63) and healthy volunteers (n = 24) were prospectively recruited and included in the study. CMR diastolic parameters were measured on cine images and velocity-encoded phase contrast cine images and compared with corresponding parameters measured on TTE. A contextual correlation feature tracking method was developed to calculate the mitral annular velocity curve. LV DD was classified by CMR and TTE following 2016 guidelines. Overall DD classification was 78.1% concordant between CMR and TTE (p < 0.0001). The trans-mitral inflow parameters correlated well between the two modalities (E, r = 0.78; A, r = 0.90; E/A, r = 0.82; all p < 0.0001) while the remaining diastolic parameters showed moderate correlation (e’, r = 0.64; E/e’, r = 0.54; left atrial volume index (LAVi), r = 0.61; all p < 0.0001). Classification of LV diastolic function by CMR showed good concordance with standardized grades established for TTE. CMR-based LV diastolic function may be integrated in routine clinical practice.Name of the registry: Technical Development of Cardiovascular Magnetic Resonance Imaging. Trial registration number: NCT00027170. Date of registration: November 26, 2001. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT00027170

Left ventricular systolic dysfunction in obesity: a meta-analysis of speckle tracking echocardiographic studies.

Obesity is a risk factor for left ventricular hypertrophy (LVH) and diastolic dysfunction. Available evidence on impaired myocardial deformation in obese patients without apparent systolic dysfunction assessed by LV ejection fraction (LVEF) is based on single studies. The aim of the present meta-analysis was to provide a comprehensive and updated information on this issue. The PubMed, OVID-MEDLINE, and Cochrane library databases were analysed to search English-language articles published from the inception up to 31 December 2023. Studies were identified by using MeSH terms and crossing the following search items: ' myocardial strain', 'left ventricular mechanics', 'longitudinal global strain', 'speckle tracking echocardiography', 'systolic dysfunction', 'left ventricular ejection fraction', and 'obesity'. Twenty-four studies including 5792 obese and 5518 nonobese individuals from different clinical settings were considered for the analysis. LV global longitudinal strain (GLS) was significantly impaired in the obese group [standard means difference (SMD): -0.86 ± 0.08; confidence interval (CI) -1.02 to -0.69, P < 0.0001] and this was paralleled by a significant difference in pooled LVEF between obese and controls (SMD -0.27 ± 0.06; CI -0.40 to -0.15, P < 0.0001). Unlike GLS, however, the majority of the selected studies failed to show statistically significant differences in LVEF. Furthermore, in patients with advanced obesity (BMI > 35 kg/m 2 , data from six studies), LV systolic dysfunction was more significantly detected by GLS (SMD -1.24 ± 0.19, CI -1.61/-0.87, P < 0.0001) than by LVEF (SMD -0.54 ± 0.27, CI -1.07 to -0.01, P = 0.046). The present meta-analysis suggests that GLS may unmask systolic dysfunction often undetected by conventional LVEF in the obese setting; thus, this parameter should be incorporated into routine work-up aimed to identify obesity-mediated subclinical cardiac damage.

Arterial Stiffness Is an Important Predictor of Heart Failure with Preserved Ejection Fraction (HFpEF)—The Effects of Phosphate Retention

Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that phosphate retention is a trigger for arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. Methods: The subjects of this study were 158 patients (68 males and 90 females, mean age 74.8 ± 11.2). HFpEF was defined according to the guidelines of the ESC 2019. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as a marker of phosphate retention. Results: The serum levels of FGF23 had a significant relationship with PWV. PWV had significant relationships with LV mass index, plasma BNP levels, and relative wall thickness, e′, and E/e′ (p &lt; 0.001, respectively). Multivariate logistic regression analysis revealed that higher PWV values and hypertension were significant predictors for the dependent factor (HFpEF). Arterial stiffness amplified afterload, leading to LV concentric hypertrophy and diastolic dysfunction. This study presents that arterial stiffness is a key predictor of HFpEF, and that phosphate retention is involved in the pathology of HFpEF.

DIASTOLIC DYSFUNCTION EVALUATION IN CARDIAC AMYLOIDOSIS: BEYOND TRADITIONAL PARAMETERS TO DISCRIMINATE BETWEEN TRUE HEART FAILURE WITH PRESERVED EJECTION FRACTION AND MIMICS

Abstract Background Diastolic dysfunction in cardiac amyloidosis (CA), according to current guidelines, can be classified using mitral flow velocities, mitral annular e’ velocity, E/e’ ratio, tricuspid regurgitation jet and left atrial (LA) maximal volume. However, LA minimal volume and the ratio between LA and left ventricular (LV) volumes at end–diastole, known as left atrio–ventricular coupling index (LACI), have recently been proposed to refine prognosis and peak atrial longitudinal strain (PALS) has been demonstrated to better stratify diastolic dysfunction. Aim of the Study To evaluate, in patients with CA: 1) the role of LACI as marker of LV diastolic dysfunction; 2) whether LACI could discriminate cardiomyopathy from normal cardiac function; 3) whether LACI and/or PALS could help discriminate between true heart failure with preserved ejection fraction (HFpEF) and amyloidotic cardiomyopathy (HFpEF–mimic). Methods We retrospectively analyzed 63 patients with CA and compared them with 80 true HFpEF patients and 70 healthy people; echocardiography was performed at the time of the diagnosis and diastolic function was characterized according to current guidelines. Results In patients with CA, LACI significantly increased as diastolic dysfunction worsened (P for trend &amp;lt; 0.0001) and significantly correlated with LV filling pressures estimated by E/e’ ratio (beta = 0.65, P &amp;lt; 0.0001) and pulmonary artery systolic pressure (beta = 0.63, P &amp;lt; 0.0001). LACI, after adjustment for age, gender and body mass index (BMI), was significantly higher in CA [0.62 (95%CI 0.52–0.70)] and in HFpEF [0.61 (95%CI 0.55–0.68)] than in controls [0.29 (95%CI 0.19–0.39)], while the difference between the two diseased populations was not statistically significant; a cut–off value of 0.45 was able to discriminate between controls and diseased patients (sensitivity = 95%, specificity = 94%, area under ROC curve = 0.98). PALS, after adjustment for age, gender and BMI, was significantly lower in CA [11.1 (95%CI 8.4–13.8%) and 8.4 (95%CI 3.5–13.3%) respectively in ATTR and AL] than in HFpEF [17.4 (95%CI 15.6–19.3%)], and a cut–off value of 9.9% was able to discriminate between them (sensitivity = 89%, specificity = 73%, area under ROC curve = 0.86). Conclusions LACI is a novel index able to discriminate between normal and diseased patients. In CA, it shows good correlation with diastolic dysfunction and LV filling pressures. PALS can be used to discriminate between true HFpEF and CA.