Significant Diastolic Dysfunction Research Articles

Assessment of LAA Strain and Thrombus Mobility and Its Impact on Thrombus Resolution—Added-Value of a Novel Echocardiographic Thrombus Tracking Method

PurposeThe mobility of left atrial appendage (LAA) thrombi and changes hereof under anticoagulation may serve as a marker of both risk of embolism and efficacy of treatment. In this study, we sought to evaluate thrombus mobility and hypothesized that LAA dynamics and thrombus mobility could serve as a baseline marker of thrombus dissolvability.MethodsPatients with two-dimensional transesophageal echocardiographic images of the LAA, and with evidence of LAA thrombus were included in this study. Using a speckle tracking algorithm, functional information from the LAA and thrombi of different patients was computed. While the LAA motion was quantified through the longitudinal strain, thrombus mobility was evaluated using a novel method by directly tracking the thrombus, isolated from the global cardiac motion. Baseline characteristics and echocardiographic parameters were compared between responders (thrombus resolution) and non-responders (thrombus persistence) to anticoagulation.ResultsWe included 35 patients with atrial fibrillation with evidence of LAA thrombi. Patients had a mean age of 72.9 ± 14.1 years, exhibited a high risk for thromboembolism (CHA2DS2-VASc-Score 4.1 ± 1.5) and had moderately reduced LVEF (41.7 ± 14.4%) and signs of diastolic dysfunction (E/E′ = 19.7 ± 8.5). While anticoagulation was initiated in all patients, resolution was achieved in 51.4% of patients. Significantly higher LAA peak strain (− 3.0 ± 1.3 vs. − 1.6 ± 1.5%, p < 0.01) and thrombus mobility (0.33 ± 0.13 mm vs. 0.18 ± 0.08 mm, p < 0.01) were observed in patients in whom thrombi resolved (i.e. responders against non-responders). Receiver operating characteristic (ROC) analysis revealed a high discriminatory ability for thrombus mobility with regards to thrombus resolution (AUC 0.89).ConclusionIsolated tracking of thrombus mobility from echocardiographic images is feasible. In patients with LAA thrombus, higher thrombus mobility appeared to be associated with thrombus resolution. Future studies should be conducted to evaluate the role of the described technique to predict LAA thrombus resolution or persistence.

Decreased Mitochondrial Unfolded Protein Response (UPRmt) in HFpEF

Mitochondrial dysfunction is a feature of heart failure with preserve ejection fraction (HFpEF). Central infusion of Ang II causes sympatho‐excitation and hypertension with consequent HFpEF. The UPRmt activation is a retrograde mitochondrial stress response that promote recovery of defective mitochondria. UPRmt is activated by misfolded accumulation of nuclear‐encoded mitochondrial proteins in cytosol and mitochondria. Despite this information, the mechanisms of UPRmt and mitochondrial dysfunction are largely unknown in the HFpEF heart. We hypothesized that concomitant sympathoexcitation with hypertension downregulates cardiac UPRmt leads to cardiac remodeling in HFpEF. Male Sprague‐Drawly rats (250‐300g) were subjected to central infusion of either Ang II (at 20 ng/min, 0.5 μl/h, ICV) or isotonic saline (0.5 μl/h, ICV, control) through osmotic mini‐pumps for 14 days. This leads to concomitant sympathetic overstimulation and systemic hypertension with myriad features of HFpEF. Transthoracic echocardiography and haemodynamic recordings were performed at day 14 post ICV infusion. UPRmt, mitochondrial injury, and cardiac remodeling were assessed using, whole‐tissue, cytosolic, and isolated mitochondrial protein Western immunoblots, cytochemistry, and histology. Sympatho‐excitatory effect on UPRmt was examined in vitro using norepinephrine (NE) and H9c2 cardiomyocytes. The HFpEF rats showed significant diastolic dysfunction indicated by reduced E/A (HFpEF: 1.2 ± 0.1 vs Con: 1.5 ± 0.2) with preserved left ventricular ejection fraction (HFpEF: 75 ± 3% vs Con: 77 ± 4%). Histological evaluation showed increased cardiomyocyte hypertrophy (HFpEF: 46.3 ± 5 vs Con: 36.9 ± 6) and cardiac fibrosis (HFpEF: 4.3 ± 0.2 vs Con: 2.1 ± 0.3). Measurement of ATF5 (Activating Transcription Factor 5), a key UPRmt activation marker was decreased in HFpEF cytosol and mitochondria, while mitochondrial chaperonin HSP60 (heat‐shock protein 60) was decreased in cytosol but increased in HFpEF mitochondria. Simultaneously, there was increased accumulation of oxidative phosphorylation (OXPH) Complex I, IV, and V misfolded subunits in the mitochondrial matrix. Furthermore, YME1L1, a mitochondrial matrix metalloprotease of misfolded protein degradation is reduced in HFpEF mitochondria. Concomitantly, there was increased mitochondrial ROS, reduced Mn‐SOD, and increased autophagy markers p62‐SQSTM1 and LC3B‐II in HFpEF hearts. Notably, a reduced mitochondrial biogenesis and fusion, but increased fission, indicates a lack of UPRmt stress activated mitochondrial recovery in HFpEF heart. Our in vitro data corroborated a reduced UPRmt in response to NE treatment associated with mitochondrial depolarization and increased mitochondrial ROS level. In conclusion, concomitant sympatho‐excitation and systemic hypertension contributes to reduced UPRmt, which is a unique feature of HFpEF heart. A lack of UPRmt activation fails to execute defective mitochondrial recovery in HFpEF heart conceivably driving HFpEF cardiac remodeling. This study identifies the key intermediary links of UPRmt downregulation in a potential HFpEF rat model. Therefore, boosting UPRmt can potentially have a therapeutic benefit for clinical HFpEF.

Correlation of ischemic Time with Diastolic Dysfunction and Correlation of Diastolic Dysfunction with 6 Minute Walk Test Distance in STEMI Patients receiving Percutaneus Coronary Intervention

Background: Minimizing the time between ischemia and reperfusion in STEMI patients is critical for salvaging ischemic myocardium and limiting residual injury. One of the methods for determining the impact of ischemic time on the myocardium and correlating the findings to the outcomes is by using echocardiography. Objectives: To evaluate the correlation of ischemic time to diastolic dysfunction and also the correlation of diastolic dysfunction to functional capacity by 6-minute walk distance in STEMI patients. Methods: The study was a retrospective cohort, with all STEMI patients who underwent PCI at RSUD Dr. Saiful Anwar Malang between January 2018 and November 2021 being eligible. All patients underwent PCI, echocardiography, and a 6-minute walk test before being discharged. We defined significant diastolic dysfunction as grade 2 or 3 diastolic dysfunction, according to the 2016 American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) guidelines. The distance of 6-minute walk test was divided into three categories: less than 300m, 300-400m, and more than 400m. Results: From total 258 patients, 92 patients (35.7%) had significant diastolic dysfunction. The significant diastolic dysfunction was correlated with ischemic time &gt; 12 hours (r = 0.51, p = 0.000), Killip class (r= 0.46, p = 0.000), culprit artery (r= 0.203, p=0,001), and peak toponin I levels (r=0.35, p=0.000). We identified that the ischemic time (odds ratio / OR 6.78; 95% Confidence Interval / CI 3.27 – 14.09; p = 0.000), Killip class (odds ratio 4.62, 95% CI 2.53 to 8.48, p = 0.000), and infarct size by peak troponin I levels (OR 1.12, 95% CI 1.06 to 1.18, p = 0.000) as independent predictors of significant diastolic dysfunction. There was inversely correlation of diastolic dysfunction with 6-minute walk test distance. (r = -0,422 dan p=0,000), with E/e’ as independent predictors of level of 6 minute walk distance (OR -1.126, 95% CI -1.78 to -0.48, p = 0.001). Conclusion: Ischemic time is one of the independent predictors of significant diastolic dysfunction. LV diastolic dysfunction was inversely correlated with 6-minute walk test distance in STEMI patient.

Stress pulmonary circulation parameters assessed by a cardiovascular magnetic resonance in patients after a heart transplant

Rest pulmonary circulation parameters such as pulmonary transit time (PTT), heart rate corrected PTT (PTTc) and pulmonary transit beats (PTB) can be evaluated using several methods, including the first-pass perfusion from cardiovascular magnetic resonance. As previously published, up to 58% of patients after HTx have diastolic dysfunction detectable only in stress conditions. By using adenosine stress perfusion images, stress analogues of the mentioned parameters can be assessed. By dividing stress to rest biomarkers, potential new ratio parameters (PTT ratio and PTTc ratio) can be obtained. The objectives were to (1) provide more evidence about stress pulmonary circulation biomarkers, (2) present stress to rest ratio parameters, and (3) assess these biomarkers in patients with presumed diastolic dysfunction after heart transplant (HTx) and in childhood cancer survivors (CCS) without any signs of diastolic dysfunction. In this retrospective study, 48 patients after HTx, divided into subgroups based on echocardiographic signs of diastolic dysfunction (41 without, 7 with) and 39 CCS were enrolled. PTT was defined as the difference between the onset time of the signal intensity increase in the left and the right ventricle. PTT in rest conditions were without significant differences when comparing the CCS and HTx subgroup without diastolic dysfunction (4.96 ± 0.93 s vs. 5.51 ± 1.14 s, p = 0.063) or with diastolic dysfunction (4.96 ± 0.93 s vs. 6.04 ± 1.13 s, p = 0.13). However, in stress conditions, both PTT and PTTc were significantly lower in the CCS group than in the HTx subgroups, (PTT: 3.76 ± 0.78 s vs. 4.82 ± 1.03 s, p < 0.001; 5.52 ± 1.56 s, p = 0.002). PTT ratio and PTTc ratio were below 1 in all groups. In conclusion, stress pulmonary circulation parameters obtained from CMR showed prolonged PTT and PTTc in HTx groups compared to CCS, which corresponds with the presumption of underlying diastolic dysfunction. The ratio parameters were less than 1.

Assessment of LAA strain and thrombus mobility and its impact on thrombus resolution - value of a novel echocardiographic thrombus tracking method

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FCT – Fundação para a Ciência e Tecnologia Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) Background The left atrial appendage (LAA) is the major nidus for thrombus in patients with non-valvular atrial fibrillation. LAA thrombus mobility and changes hereof under anticoagulation may serve as a marker of both risk of embolism and efficacy of treatment. In this study, we hypothesized that LAA dynamics and thrombus mobility could serve as a baseline marker of thrombus dissolvability. Methods Transesophageal echocardiographic (TEE) images of in whom LAA thrombi were previously diagnosed were evaluated. Each image was tracked using a state-of-the-art tracking toolbox and functional information from the LAA and thrombi extracted. Global LAA motion was quantified through the longitudinal strain, while thrombus mobility was measured through a novel tracking scheme by directly capturing and measuring the thrombus motion isolated from the global cardiac motion. Baseline characteristics and echocardiographic parameters were compared between responders (thrombus resolution, i.e. no thrombus found at follow-up TEE) and non-responders (thrombus persistence or growth, i.e. thrombus found at follow up TEE) groups. Results 35 patients (54.3% male and 45.7% female) with a mean age of 72.9 ± 14.1 years were included. Atrial fibrillation was present in all patients, showing a high risk for thromboembolism (CHA2DS2-VASc-Score 4.1 ± 1.5). Moderately reduced LVEF (41.7 ± 14.4%) and signs of diastolic dysfunction (E/E’ = 19.7 ± 8.5) was found in the cohort. While anticoagulation was initiated in all patients, resolution was achieved in 51.4% of patients. Significantly higher thrombus mobility (0.33 ± 0.13mm vs. 0.18 ± 0.08mm, p &amp;lt; 0.01 – Figure 1A) and LAA peak strain (-3.0 ± 1.3 vs -1.6 ± 1.5%, p &amp;lt; 0.01 – Figure 1B) were observed in responders against the non-responders group. Conclusions The quantification of the thrombus mobility through a tracking scheme is feasible. In our study population, higher thrombus mobility appeared to be associated with thrombus resolution. Further studies are required to evaluate the additional prognostic of the proposed technique. Figure 1 – Quantification of the thrombus mobility (A) and peak LAA longitudinal strain (B) in both responder (blue) and non-responder group (green). *p &amp;lt; 0.05, unpaired t-test between non-responder and responder groups. Abstract Figure 1

Left Ventricular Diastolic Dysfunction Screening by a Smartphone-Case Based on Single Lead ECG.

Aims:To investigate the potential of a signal processed by smartphone-case based on single lead electrocardiogram (ECG) for left ventricular diastolic dysfunction (LVDD) determination as a screening method.Methods and Results:We included 446 subjects for sample learning and 259 patients for sample test aged 39 to 74 years for testing with 2D-echocardiography, tissue Doppler imaging and ECG using a smartphone-case based single lead ECG monitor for the assessment of LVDD. Spectral analysis of ECG signals (spECG) has been used in combination with advanced signal processing and artificial intelligence methods. Wavelengths slope, time intervals between waves, amplitudes at different points of the ECG complexes, energy of the ECG signal and asymmetry indices were analyzed. The QTc interval indicated significant diastolic dysfunction with a sensitivity of 78% and a specificity of 65%, a Tpeak parameter >590 ms with 63% and 58%, a T value off >695 ms with 63% and 74%, and QRSfi > 674 ms with 74% and 57%, respectively. A combination of the threshold values from all 4 parameters increased sensitivity to 86% and specificity to 70%, respectively (OR 11.7 [2.7-50.9], P < .001). Algorithm approbation have shown: Sensitivity—95.6%, Specificity—97.7%, Diagnostic accuracy—96.5% and Repeatability—98.8%.Conclusion:Our results indicate a great potential of a smartphone-case based on single lead ECG as novel screening tool for LVDD if spECG is used in combination with advanced signal processing and machine learning technologies.

C18. Cardiac AA amyloidosis presenting with refractory heart failure complicated by polymorphic ventricular tachycardia: a case report

Abstract Background Systemic AA amyloidosis is a rare infiltrative disease representing a complication of chronic inflammatory disorders. Cardiac involvement is rare and is associated with a poor prognosis. Early recognition is imperative as appropriate measures, and treatment of the underlying disease may prevent death from refractory heart failure and fatal arrhythmias. Case Summary A 53-years-old male patient with psoriatic arthritis presented with heart failure and nephrotic syndrome. Electrocardiogram revealed first-degree AV block, low voltage QRS complexes, and prolonged QT interval. On echocardiography, a normal systolic function of hypertrophic left ventricle with signs of diastolic dysfunction was present. An abdominal fat pad punch biopsy was able to confirm amyloid deposition. Self-terminated polymorphic ventricular arrhythmia was recorded by 24-hour Holter. Immunosuppressive, anti-inflammatory, anti-arrhythmic, and heart failure agent were promptly instituted, which are ineffective. Discussion Restrictive cardiomyopathy is the hallmark finding in cardiac amyloidosis that caused by the interstitial deposits of amyloid fibrils. Clinically, this manifests in progressive diastolic dysfunction, elevated left ventricular filling pressures, and heart failure with preserved ejection. The presence of rapidly progressed heart and renal failure with characteristic features of ECG should prompt further evaluation to confirm an infiltrative cardiomyopathy. This is highly suggestive that the natural course of cardiac amyloidosis often unpredictable and can be aggressive if left undiagnosed and untreated.

C18. Cardiac AA amyloidosis presenting with refractory heart failure complicated by polymorphic ventricular tachycardia: a case report

Abstract Background Systemic AA amyloidosis is a rare infiltrative disease representing a complication of chronic inflammatory disorders. Cardiac involvement is rare and is associated with a poor prognosis. Early recognition is imperative as appropriate measures, and treatment of the underlying disease may prevent death from refractory heart failure and fatal arrhythmias. Case Summary A 53-years-old male patient with psoriatic arthritis presented with heart failure and nephrotic syndrome. Electrocardiogram revealed first-degree AV block, low voltage QRS complexes, and prolonged QT interval. On echocardiography, a normal systolic function of hypertrophic left ventricle with signs of diastolic dysfunction was present. An abdominal fat pad punch biopsy was able to confirm amyloid deposition. Self-terminated polymorphic ventricular arrhythmia was recorded by 24-hour Holter. Immunosuppressive, anti-inflammatory, anti-arrhythmic, and heart failure agent were promptly instituted, which are ineffective. Discussion Restrictive cardiomyopathy is the hallmark finding in cardiac amyloidosis that caused by the interstitial deposits of amyloid fibrils. Clinically, this manifests in progressive diastolic dysfunction, elevated left ventricular filling pressures, and heart failure with preserved ejection. The presence of rapidly progressed heart and renal failure with characteristic features of ECG should prompt further evaluation to confirm an infiltrative cardiomyopathy. This is highly suggestive that the natural course of cardiac amyloidosis often unpredictable and can be aggressive if left undiagnosed and untreated.

Abstract 14305: Diastolic Dysfunction and Activation of Ventricular and Atrial Unfolded Protein Response in a Novel Gottingen Miniswine Model of Heart Failure With Preserved Ejection Fraction

Introduction: During cardiac hypertrophy, the unfolded protein response (UPR) is activated which includes upregulation of chaperones to assist with protein folding and protein ubiquination for proteolytic degradation. We investigated the expression level of a key chaperone Hspa5 (heat shock protein A5) and ubiquinated protein levels in left ventricular (LV) and atrial (LA) tissue obtained from a preclinical porcine model heart failure with preserved ejection fraction (HFpEF) involving obesity and hypertension. Methods: Female Gottingen minipigs were fed standard or western diet (WD) for 20 weeks to induce obesity and metabolic syndrome and subsequent HFpEF. Those fed WD were also administered 11-deoxycorticosterone acetate (DOCA) (50 mg/kg, SQ) to induce hypertension. LV functional assessment was performed via transthoracic echocardiography and invasive hemodynamics at 20 weeks. In addition, UPR and proteasomal function were assayed following 20 weeks of HFpEF in ventricular and left atrial extracts via RT-qPCR and immunoblot. Results: Minipigs fed WD+DOCA demonstrated hypercholesterolemia, hypertension, LV hypertrophy and increased LVEDP. LVEF was &gt;50% in HFpEF and control groups. We observed significant LV diastolic dysfunction as measured by E/e’ and LA dysfunction as decreased LA fractional area of change (LAFAC) at 20 weeks. LV extracts from HFpEF swine demonstrated a marked increase in Hspa5 without measurable increases in standard fetal genes (e.g. Myh7 ). LA extracts from HFpEF swine exhibited robust accumulation of ubiquitylated proteins compared to control swine. There was a positive correlation between Hspa5 and E/e’ ratio, and the inverse for LA ubiquitylated proteins and LA function. Conclusions: Coordinate with myocardial stiffening, hypertrophy and functional decline, HFpEF robustly augments proteostasis in both LV myocardium and LA recapitulating the clinical presentation of HFpEF patients.

Assessment of Right Ventricular Function and Structure in Children with Idiopathic Dilated Cardiomyopathy

Background: Dilated cardiomyopathy (DCM) refers to dilating the ventricles and dysfunction of their systolic functions (predominantly the left ventricle) with or without congestive heart failure. In children, it is the most common form of heart muscle disease. We aimed to evaluate the right ventricular functions and structure using speckling tracking echocardiography in children with dilated cardiomyopathy and correlate this parameter with other echocardiographic findings.&#x0D; Methods: This observational Case-Control Study was carried out on 75 subjects. They were subdivided into two groups: Group 1: 50 patients with dilated cardiomyopathy Group 2: 25 healthy children matched for age and sex. Patients were evaluated by M-mode echocardiography, Transthoracic 2DE Examination (TTE), Tissue Doppler Examination (TDE) and Speckling Tracking Technique.&#x0D; Results: Left ventricle (LV) and right ventricle (RV) systolic dysfunction was evidenced by a significant decrease of mitral and tricuspid annular systolic velocities and a significant decrease of LV and RV global systolic strain and a significant decrease of LV and RV Ejection fraction (EF). LV and RV diastolic dysfunction were evidenced by a significant decrease of mitral and tricuspid annular diastolic velocities (E’/A’) and a significant increase of LV and RV Myocardial Perfusion Imaging (MPI). LV and RV global strains were significantly reduced in comparison to controls, suggesting that the dilated cardiomyopathy is a diffuse disease.&#x0D; Conclusion: In DCM patients, RV had significant systolic and diastolic dysfunction mainly elicited by the Tissue Doppler imaging (TDI) beside LV affection secondary to the interventricular interaction. TDI and 2D-STE add value to interpreting the findings and the dependency of RV systolic and diastolic functions on each other in DCM patients.

Serum Leptin In Ischemic Heart Disease Patients With And Without Significant Diastolic Dysfunction In Lean And Obese Patients; Cross Sectional Study

Abstract Background Cardiovascular diseases represent the leading cause of mortality worldwide. Ischemic heart disease is one of the main causes of diastolic heart failure and its presence predicts a poor prognosis in ischemic heart patients. Most cardiovascular diseases can be prevented by addressing behavioral risk factors such as overweight and obesity. Leptin –also known as satiety hormone- helps in inhibiting hunger and regulate energy balance (1). Objective to correlate leptin level with ischemic heart disease with or without diastolic dysfunction by comparing it in lean and obese patients. Material and Methods from June 2019 to November 2019, 140 ischemic patients documented with CA, MSCT or history of PCI AND 35 Control subjects were enrolled from both Ain Shams University, Cardiology department wards and outpatient clinic and Misr University for science and technology, cardiology department wards and outpatient clinic. All participants subjected to history, clinical examination, Duke CAD index to estimate the severity of ischemia, calculation of their BMI, blood sampling for measuring their serum leptin level and echocardiography for detecting the diastolic function. Patients were divided into four groups according to their BMI and Diastolic function in addition to the control group. Groups were demonstrated as follow Group A lean ischemic patients without significant diastolic dysfunction, Group B lean ischemic patients with diastolic dysfunction (II-IV), Group C obese ischemic patients without significant diastolic dysfunction, Group D obese ischemic patients with diastolic dysfunction(II-IV), Group E is a control group lean non ischemic without diastolic dysfunction . Results There were significant positive correlations between serum leptin and Duke score in all ischemic groups (n = 140) (p &amp;lt; 0.001). Serum leptin abnormality was significantly more frequent in diastolic dysfunction groups (n = 70) than in non-dysfunction groups (N = 70) (Group B 25.7%, group D 28.6% vs group A 5.7% group C 8.6%, also was lowest in control group (n = 35) 0.0%. serum leptin was significantly positive correlated with ischemia as in group A17.8±2.1ng/mL group B 23.4±11.1ng/mL group C 55.4±10.9 ng/mL group D 65.2±10.8 ng/mL vs control group E 13.1±2.7 ng/mL. Conclusion leptin is an independent risk factor for coronary heart disease. Also elevated plasma leptin levels are associated with impaired left ventricular diastolic function in patients with CAD independently of obesity and other confounding variables.

Early Cardiac Dysfunction in Biopsy-proven Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) encompasses a range of diseases from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and has been linked to cardiovascular disease and sub-clinical cardiac remodeling. This paper presents a retrospective study of biopsy-proven NAFL and NASH to examine the differences in subclinical cardiac remodeling. Patients were recruited from an institutional repository of patients with liver-biopsy-confirmed NAFLD. Patients with a transthoracic echocardiogram (TTE) within 12 months of the liver biopsy were included. The parameters of the diastolic dysfunction were reviewed for the differences between NAFL and NASH as well as between the stages and grades of NASH. Thirty-three patients were included in the study, 17 with NAFL and 16 with NASH. The NASH patients were more likely to have lower platelets, higher AST, higher ALT, and higher rates of type 2 diabetes mellitus, coronary artery disease, and hypertension than the NAFL patients. The E/e' ratio on transthoracic echocardiogram was significantly higher in NASH compared to NAFL, advanced-stage NASH compared to early stage, and high-grade NASH compared to low-grade. The E/e' ratio was also significantly higher in NASH than NAFL in patients without diabetes mellitus. The presence of diastolic dysfunction trended toward significance. The other markers of diastolic dysfunction were similar. Logistic regression revealed a statistical association with E/e' and NASH. NASH patients had evidence of a higher E/e' ratio than NAFL, and there was a trend towards a significant diastolic dysfunction. Patients with NASH compared to NAFL should be closely monitored for signs and symptoms of cardiac dysfunction.

Імунно-запальні предиктори розвитку діастолічної дисфункції лівого шлуночка у хворих на ревматоїдний артрит в поєднанні з артеріальною гіпертензією

Hypertension is the most common concomitant disease in patients with rheumatoid arthritis. Diastolic dysfunction of left ventricle is an important predictor of chronic heart failure, which can be asymptomatic for a long time. Therefore, it is advisable to detect diastolic dysfunction of left ventricle as early as possible, which can slow the progression of chronic heart failure. The purpose of the study was to determine the value of lipid peroxidation, endothelial function and systemic inflammatory response markers for diagnostic of diastolic dysfunction of left ventricle and for diagnostic of pericardial effusion in patients with rheumatoid arthritis combined with hypertension. Materials and methods. 93 patients with rheumatoid arthritis in combination with stage II hypertension were studied. The ultrasound examination of heart was performed. The serum laboratory markers of lipid peroxidation, concentration of pro-inflammatory cytokines, markers of endothelial function were determined. Results and discussion. Signs of diastolic dysfunction of left ventricle were found in 79 patients and no signs of diastolic dysfunction were found in 14 patients. It was detected that there was a significant increase of concentration of asymmetric dimethylarginine by 16.3%, interleukin-1β by 35.3%, interleukin-10 by 24.3%, the ratio of interleukin-1β / interleukin-10 by 62.0%, C-reactive protein by 52.6% and there was a significant decrease of total nitric oxide metabolites by 36.9%, nitrires by 37.5% and nitrates by 37.0% in patients with signs of diastolic dysfunction of left ventricle compared to the patients without diastolic dysfunction of left ventricle (p &lt;0.01). It was found that the levels of isolated double bonds, diene conjugates, diene ketones, schiff bases and malonic aldehyde in patients with diastolic dysfunction of left ventricle were significantly higher by 24.4%, 25.2%, 20.4%, 17.6% and 21.4% respectively compared to the corresponding markers in patients without signs of diastolic dysfunction of left ventricle (p &lt;0.01). The levels of vitamin A, vitamin E and catalase in patients with diastolic dysfunction of left ventricle were significantly lower by 18.2%, 27.4% and 13.4% compared to the corresponding markers of patients with normal left ventricle diastolic function (p &lt;0.01). The highest predictor value for the diagnostic of diastolic dysfunction of left ventricle was detected in interleukin-1β area under the ROC curve 0.882, sensitivity 72.15% and specificity 100%, 95% CI [0.798-0.939] at the optimal distribution point &gt;9.67 pg/ml and in asymmetric dimethylarginine area under the ROC curve 0.879 sensitivity 75.95% and specificity of 100%, 95% CI [0.795-0.937] at the optimal distribution point &gt;0.715 μmol/l. In 17 (18.28%) patients, the effusion in the pericardial cavity was detected. It was detected that there was a significant increase of isolated double bonds by 18.65%, diene conjugates by 19.73%, diene ketones by 25.25%, schiff bases by 20%, malonic aldehyde by 26.76% and there was a significant decrease of vitamin A by 38.4%, vitamin E by 55.4% and catalase by 37.2% in patients with effusion in the pericardial cavity. The significant increase of asymmetric dimethylarginine was detected by 25.25%, interleukin-1β – by 52.24%, interleukin-10 – by 15.76%, the ratio of interleukin-1β / interleukin-10 – by 38.86% and C-reactive protein – by 26.9% in patients with effusion in the pericardial cavity. In addition, patients with cavity effusion have significant decrease of nitric oxide metabolites by 25.0%, nitrires by 30.0% and nitrates by 11.11% compared to the patient without effusion. The highest predictor value for the detection of effusion in the pericardial cavity was found in asymmetric dimethylarginine area under the ROC curve 0.913, 95% CI area under the ROC curve [0.836-0.961] at the optimal distribution point &gt;0.841 μmol/l, sensitivity 94.12% and specificity 85.53%. Conclusion. The markers, which have the highest prognostic value for diagnostic of diastolic dysfunction of left ventricle in patients with rheumatoid arthritis combined with hypertension, are interleukin-1β and asymmetric dimethylarginine. In addition, asymmetric dimethylarginine has the highest predictor value for detecting fluid in the pericardial cavity

Abstract P364: Liraglutide Protects Against Angiotensin-induced Diastolic Dysfunction And Is Associated With Altered Acetyl-coa Metabolism

Background: The mechanisms underlying diastolic dysfunction remain complicated and poorly understood. Previously implicated mechanisms include increased interstitial fibrosis and oxidative damage, altered calcium handling, and mitochondrial dysfunction. In this study, we investigate changes in the cardiac metabolic profile from mice with Angiotensin-II (Ang)-induced diastolic dysfunction. Because treatment with the GLP-1 agonist liraglutide (Lira) relieves Ang-induced diastolic dysfunction, we examined altered metabolites in Ang and Ang+Lira mice to identify metabolic pathways involved. Methods: 8-wk mice were implanted with Ang pumps (1000 ng/kg/min) +/- Lira (0.2 mg/kg/day) therapy for 4 wks and compared to sham mice. Baseline and 4-wk echocardiography was performed. Hearts were collected for RNA-sequencing, Western blot, histology, radiolabeled palmitate assay, and targeted metabolomics by liquid chromatography-mass spectrometry to assess metabolic changes. Results: After Ang treatment, mice had significant diastolic dysfunction but only mild hypertrophy based on echo and histologic measures and no evidence of systolic change. Compared to sham mice, Ang mice had reduced E/A (Sham, 2.67±0.40; Ang, 1.71±0.11; p&lt;0.05) and peak reverse longitudinal strain rate (rLSR;Sham, 8.48±0.65/s; Ang, 6.081±0.33/s; p&lt;0.05, consistent with diastolic dysfunction. Ang+Lira mice had improved E/A (3.57±0.50, p&lt;0.01 vs. Ang) and rLSR (8.65±0.68/s, p&lt;0.01 vs Ang). Targeted metabolomic analysis of hearts found significantly increased accumulation of Acetyl-CoA in Ang mice (peak area 0.14±0.02) compared to sham (0.04±0.02 ,p&lt;0.05) that is restored by Lira therapy (0.02±0.01 ,p&lt;0.05 vs sham and Ang). A radiolabeled palmitate oxidation assay found decreased palmitate oxidation in both Ang and Ang+Lira mice compared to sham, but interestingly, also demonstrated significantly lower acid soluble metabolite oxidation in the Ang+Lira mice vs. Ang alone. Conclusions: We found that Ang-treated mice accumulate myocardial Acetyl-CoA, suggesting a defect in TCA flux. Lira resolves the increase in Acetyl-CoA and improved measures of diastolic dysfunction. This data may implicate a novel metabolic pathway in the development of diastolic disease.

Pericardial Constriction and Myocardial Restriction in Pediatric Mulibrey Nanism: A Complex Disease With Diastolic Dysfunction

BackgroundMulibrey nanism (MUL) is a rare condition with profound growth delay. Congestive heart failure is a major determinant of prognosis. The aim was to delineate pericardial constriction and myocardial functional abnormalities in a pediatric MUL sample. MethodsA total of 23 MUL patients and 23 individually sex- and age-matched healthy control subjects were prospectively assessed in a cross-sectional study with echocardiography. ResultsClinical signs of heart failure were present in 7 MUL patients, with severe congestive heart failure in 2. Significant diastolic dysfunction, mainly related to constriction, was found in MUL patients without pericardiectomy (N = 18)—septal bounce, pronounced hepatic vein atrial reversal and right heart inflow–outflow variations, and decreased inferior vena cava collapse during respiration. The appearance of the pericardium was not different from that of control subjects. Longitudinal diastolic myocardial velocities were similar to those in control subjects, suggesting an absence of significant myocardial restriction. Right ventricular free wall longitudinal systolic strain and bilateral longitudinal myocardial systolic velocities were decreased in MUL patients, indicating mild biventricular systolic dysfunction. Myocardial motion abnormalities and persistent congestive heart failure were common (in 3 of 6) in MUL patients with a history of pericardiectomy. Cardiac dimensions were similar between MUL patients and control subjects when adjusting for body size, except for smaller biventricular volumes. ConclusionsMUL disease presents with significant constriction-related diastolic dysfunction and mild bilateral systolic dysfunction. Constriction–restriction assessments during follow-up could be of benefit in decision-making regarding pericardiectomy in MUL disease. Myocardial abnormalities were prevalent among MUL patients who had undergone pericardiectomy and are consistent with progression of myocardial disease in a significant proportion of patients.

Metabolic improvement with short-term, glucagon-like peptide-1 receptor agonist treatment does not improve cardiac diastolic dysfunction in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

To investigate if short-term treatment with liraglutide, a glucagon-like peptide-1 receptor agonist, improves left ventricular diastolic function. An investigator-initiated, double-blind, randomized, placebo-controlled trial on the effect of 18 weeks of treatment with liraglutide on diastolic function was assessed in patients with type 2 diabetes with signs of diastolic dysfunction (echo-Doppler determined E/e' ≥ 9 and/or lateral e' ≤ 10cm/s). Primary outcomes were improved left ventricle filling (the early peak filling rate [ePFR]) and left atrium ease of emptying (the passive emptying fraction [LAPEF ]), assessed by cardiac magnetic resonance imaging at rest and during chronotropic stress. Secondary outcomes included left ventricular and left atrial volumes and systolic function, measures of aortic stiffness and echocardiographic diastolic variables. Forty patients were randomized to liraglutide subcutaneously 1.8 mg/day (n=20) or placebo (n=20). Liraglutide reduced HbA1c (-0.47%, 95% CI [-0.88% to -0.06%] [-5.1, 95% CI {-9.7 to -0.62} mmol/mol]) and weight (-2.9, 95% CI [-4.6 to -1.2] kg); both P < .03. Liraglutide did not change ePFR at rest (-24 ± 60 vs. -6 ± 46 mL/s), during stress (2 ± 58 vs. -2 ± 38 mL/s), or the changes from rest to stress (12.9 ± 72.5 vs. 4.7 ± 104.0; all P > .05). LAPEF decreased with liraglutide during stress (-3.1% [-9.0%, 1.1%] vs. 1.0% [-2.9%, 6.1%]; P=.049), but no changes were evident at rest (-4.3% [-7.9%, 1.9%] vs. -0.6% [-3.1%, 2.2%]; P=.19), or for the changes from rest to stress (-1.7 ± 8.4 vs. 0.8 ± 8.2; P=.4). Secondary outcomes were unchanged by liraglutide. Short-term treatment with liraglutide did not improve left ventricular diastolic function, suggesting the cardioprotective effect is not exerted through the improvement in diastolic dysfunction.

Fibrosis biomarkers and global myocardial strain in the diagnosis and prediction of diastolic dysfunction in patients with myocardial infarction and preserved ejection fraction

Aim. To assess the correlation of fibrosis biomarkers with parameters of diastolic function (DF) in assessing global longitudinal strain in patients with ST-segment elevation myocardial infarction (STEMI) and preserved left ventricular ejection fraction (EF).Material and methods. We examined 50 patients (100%) with primary STEMI and preserved LVEF at the end of hospitalization. On the 1st day of MI, standard diagnostic investigations were carried out. On the 12th day, the serum concentration of procollagen type I carboxy-terminal propeptide (PICP), N-terminal propeptide of procollagen type III (PIIINP), and galectin-3 was determined, as well as echocardiography was performed to assess left ventricular DF. After 1 year, all participants underwent reassessment of PICP, PIIINP, and galectin-3 serum levels. Echocardiography was also performed with an assessment of DF and LV global longitudinal strain.Results. According to speckle-tracking echocardiography, LV global longitudinal strain was visualized in 30 patients (60%), who were included in the final analysis. In the rest of the patients (40%), the limitations did not allow the technique to be performed. During the hospitalization, signs of diastolic dysfunction (DD) were detected in 5 (16,6%) patients; after 1 year, their number increased by 7 (23,3%). During the 1-year follow-up, the total number of patients with echocardiographic signs of DD was 20 (67%). At the same time, global strain parameters indicated the presence of DD in 23 (77%) patients. However, comparison of the incidence of DD according to echocardiography and using the speckle-tracking technology did not show significant differences (p=0,283). Throughout the entire follow-up period, the concentration of the studied fibrosis markers significantly exceeded the control group values. We recorded associations of global strain parameters with biochemical markers of fibrosis and LV DF indicators.Conclusion. Fibrosis biomarkers (PICP, PIIINP, galectin-3), assessed in the subacute period of MI in patients with preserved EF, correlated with indicators of global myocardial strain, which indicates the potential value of their determination for predicting and detecting DD in the postinfarction period.

Signs of diastolic dysfunction are graded by serum testosterone levels in aging C57BL/6 male mice

We investigated whether maladaptive, age-associated changes in heart structure and function were linked to circulating testosterone levels. Male C57BL/6 mice had a gonadectomy (GDX) or sham surgery at 4 weeks and effects of GDX on the heart were examined with echocardiography. Serum testosterone was measured with ELISA. Left ventricular (LV) mass increased with age but was smaller in GDX mice than sham at 18 months (144.0 ± 8.7 vs 118.2 ± 11.9 mg; p = 0.009). The isovolumic relaxation time (IVRT) declined with age but was prolonged in GDX mice at 18 months (10.5 ± 0.8 vs 12.5 ± 0.5 msec, p = 0.008). Ejection fraction did not change with age or GDX, but E/A ratios were lower in GDX mice than controls at 18 months (1.6 ± 0.2 vs 1.3 ± 0.1, p = 0.021). When links between serum testosterone and cardiac parameters were examined longitudinally in 18−24-month-old mice, LV mass declined with decreasing testosterone (β = 37.70, p = 0.016), however IVRT increased as testosterone decreased (β=−2.69, p = 0.036). Since longer IVRT and lower E/A ratios are signs of diastolic dysfunction, low circulating testosterone may promote or exacerbate diastolic dysfunction in older males. These findings suggest that lower testosterone directly modifies heart structure and function to promote maladaptive remodeling and diastolic dysfunction in the aging heart.

Clinical relevance of spectral tissue Doppler-derived E/e′ in older patients with preserved ejection fraction

BackgroundThe E/e′ index measured in spectral tissue Doppler is included in the recommendations for the diagnosis by transthoracic Doppler echocardiography of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction. While E/e′ is influenced by age in healthy individuals, no studies have evaluated this index in elderly patients. This study addressed the clinical relevance of E/e′ in assessment of left ventricular diastolic function in elderly patients with preserved ejection fraction and its relevance from both a diagnostic and prognostic perspective based on the existing literature. MethodsA total of 76 patients≥70years of age were prospectively included. The analysis of left ventricular diastolic function was adapted from the 2016 ASE/EACVI recommendations without consideration of E/e′. ResultsThe mean age was 85years. In all, 42 patients had moderate-to-severe diastolic dysfunction (elevated left atrial pressure). Mean E/e′ was significantly correlated with diastolic function (r=0.58, P<0.001). Mean E/e′>13.3 had a sensitivity of 86% and a specificity of 91% in the diagnosis of moderate-to-severe diastolic dysfunction (AUC: 0.92). E/(e′xs′) (AUC: 0.89) and NT pro-BNP (AUC: 0.80) did not perform better than E/e′. The existing literature offers large body of evidence that E/e′ provides essential diagnostic and prognostic information in older patients with cardiovascular disease. ConclusionE/e′ is accurate in the diagnosis of significant diastolic dysfunction, in the diagnosis of heart failure with preserved ejection fraction and in risk stratification in older patients with cardiovascular disease.

Cardiac abnormalities determined by tissue Doppler imaging and arrhythmias in adolescents with anorexia nervosa.

Anorexia nervosa has a prevalence of 0.5-3% in adolescents, placing this population at increased risk of cardiac anomalies including arrhythmias, pericardial effusion, and myocardial dysfunction. Our objective is to describe cardiovascular anomalies observed by tissue Doppler imaging in patients with anorexia nervosa. We retrospectively reviewed electrocardiogram, Holter, and echocardiography findings in 28 patients diagnosed with anorexia nervosa. Electrocardiogram was abnormal in 71% of patients with sinus bradycardia observed in 57%. Holter confirmed sinus bradycardia without significant pauses. Prolonged QTc, low voltage, and ectopic beats were each seen in 14% of patients. Wenckebach atrioventricular block was observed in one patient. Supraventricular or ventricular tachycardia was not observed. Echocardiography showed structurally normal heart in all patients. Pericardial effusion was seen in 7.1% of patients and left ventricular mass was decreased in 10.7%. Mean ejection fraction was 0.73 and mean fractional shortening was 38.4%. Tissue Doppler imaging revealed systolic or diastolic dysfunction in four patients with e', a', and s' velocities in the lateral and septal basal segments more than two standard deviations below the mean. Two patients had decreased left ventricular mass but no significant difference in disease duration from the group. Basal segment velocities below one standard deviation were also observed in an additional seven patients. A trend for decreased tissue Doppler imaging velocities was seen in 25.0% of patients, while significant systolic and diastolic dysfunction was seen in 14.3% of patients, associated with a significant reduction in left ventricular mass and independent of disease duration.