Ventricular Diastole Research Articles

Aortic Stiffness and Cardiac Modification After Open or Endovascular Aortic Treatment: Preliminary Results of a Single-Center Prospective Cohort Study

Increased aortic stiffness (AoS), is considered an independent marker of cardiovascular mortality and morbidity. Aortic endovascular treatment correlates to a worsening of AoS, indirectly evaluated with pulse wave velocity (PWV). This could lead to changes in cardiac geometry and efficiency over time. The aim of this study is to evaluate possible changes in AoS with consequent alterations in cardiac function after endovascular (ER) or open (OR) repair, also analyzing different endograft fabric. Patients who were candidate for elective ER or OR for different abdominal aortic disease were enrolled. PWV was measured during the preoperative period and after 1 year. Doppler echocardiography was performed before surgery and after 1 year evaluating arterial (Ea) and ventricular (Ees) elastance and their coupling (Ea/Ees), left ventricular left atrial volume index and left atrial volume index, ejection fraction, and ratio of early ventricular filling to atrial systole (E/A). Furthermore, systolic and diastolic blood pressure and exercise tolerance by the Specific Activity Scale score were assessed preoperatively and after one-year. All data were compared between ER and OR groups and between endo-PTFE and endo-Polyester group. Sixty patients have been enrolled in the 2-year period from 2019 to 2021 (19 OR and 41 ER). Both groups were homogeneous considering cardiovascular risk factors, except for age, which was lower for the OS group (67.2 ± 7.2 vs 75.4 ± 6.4 years; P < .001). Fifty-one patients completed the follow-up (13 OR, 38 ER). PWV increased in both groups, significantly in ER (+2.9 m/second; P = .016). Systolic blood pressure grew in both ER (+20.2 mm Hg; P < .001) and OR groups (+18.4 mm Hg; P = .005). Diastolic blood pressure grew in ER group (+5.2 mm Hg; P = .009) Ea increased +0.3 mm Hg/mL/m2 in both ER and OR groups (P = .026; P = .020), without significant changes in Ea/Ees coupling. E/A ratio decreased (−0.1; P < .001) in the ER group. No significant changes in left ventricular left atrial volume index, left atrial volume index and ejection fraction were recorded (Table I). In ER group, the Specific Activity Scale score got worse (+0.3; P = .004) and three cardiac events were recorded. Considering the subanalysis endo-PTFE vs endo-Polyester, PWV (+3.8 m/second; P = .023) and Ea (+0.4 mm Hg/mL/m2; P = .008) increased significantly in endo-Polyester group only (Table II). AoS increases after ER, mostly in patients with a polyester-covered device. Furthermore, the reversal of E/A ratio means an initial alteration in ventricular diastole, not related to significant mid-term changes in cardiac geometry. These changes could lead to diastolic disfunction with an increased risk of cardiovascular events over time. Further investigation is needed to validate our results.Table IPulse wave velocity (PWV), pressures and echocardiographic data after 1 year of follow-up in the open repair (OR) and endovascular repair (ER) groupsCharacteristicsOR (n = 13)P < .05ER (n = 38)P < .05Preoperative1 YearPreoperative1 YearPWV (m/second)11.6 ± 5.215.5 ± 8.1.05712.7 ± 3.615.6 ± 6.3.016SBP (mm Hg)132.9 ± 22.8151.3 ± 15.9.005134.7 ± 15.6154.9 ± 16.9<.001DBP (mm Hg)78.2 ± 8.481.9 ± 8.5.41573.9 ± 9.979.1 ± 8.4.009LVVi (mL/m2)50.3 ± 1257 ± 15.2.35948.1 ± 17.350.9 ± 16.2.093LAVi (mL/m2)31.5 ± 8.334.5 ± 13.6.89831.9 ± 6.634.9 ± 11.6.378EF (%)60 ± 5.758 ± 6.8.21559.4 ± 6.358.8 ± 6.1.604E/A ratio0.8 ± 0.31 ± 0.5.2500.8 ± 0.20.7 ± 0.2<.001Ea (mm Hg/mL/m2)1.4 ± 0.31.7 ± 0.4.0201.5 ± 0.51.8 ± 0.5.026Ees (mm Hg/mL/m2)1.6 ± 0.81.9 ± 0.5.1481.6 ± 0.61.7 ± 0.6.188Ea/Ees1 ± 0.30.9 ± 0.2.5781 ± 0.31.1 ± 0.3.740DBP, Diastolic blood pressure; Ea, arterial elastance; E/A, early ventricular filling to atrial systole ratio; Ees, ventricular end-systolic elastance; EF, ejection fraction; LAVi, left atrial volume index; LVVi, left ventricular volume index; SBP, systolic blood pressure.All data are reported as mean ± standard deviation. Open table in a new tab Table IIPulse wave velocity (PWV), pressures and echocardiographic data after 1 year of follow-up in endo-PTFE and endo-Polyester group.CharacteristicsEndo-PTFE (n = 15)P < .05Endo-Polyester (n = 23)P < .05Preoperative1 YearPreoperative1 YearPWV (m/second)11.7 ± 3.114 ± 4.6.09112.9 ± 3.116.7 ± 7.1.023SBP (mm Hg)128.7 ± 16.7157.3 ± 19.5<.001138.7 ± 13.9153.3 ± 15.1<.001DBP (mm Hg)68.7 ± 8.179 ± 7.1.00277.3 ± 9.479.1 ± 9.3.356LVVi (mL/m2)44.9 ± 9.647.7 ± 9.2.18450.2 ± 20.753 ± 19.4.330LAVi (mL/m2)32.8 ± 6.736.5 ± 13.2.31331.3 ± 6.833.9 ± 10.7.685EF (%)59.2 ± 4.158.9 ± 3.7159.5 ± 7.558.8 ± 7.2.557E/A ratio0.9 ± 0.30.7 ± 0.2.0160.8 ± 0.20.7 ± 0.2.001Ea (mm Hg/mL/m2)1.7 ± 0.71.7 ± 0.5.6071.4 ± 0.31.8 ± 0.5.008Ees (mm Hg/mL/m2)1.6 ± 0.71.8 ± 0.7.1761.6 ± 0.71.7 ± 0.6.637Ea/Ees1.1 ± 0.31 ± 0.3.5701 ± 0.31.1 ± 0.3.391DBP, Diastolic blood pressure; Ea, arterial elastance; E/A, early ventricular filling to atrial systole ratio; Ees, ventricular end-systolic elastance; EF, ejection fraction; LAVi, left atrial volume index; LVVi, left ventricular volume index; SBP, systolic blood pressure.All data are reported as mean ± standard deviation. Open table in a new tab

Aortic Isthmus Retrograde Blood Flow in Intrauterine Child as a Sign of the Terminal Stage of Placental Dysfunction: Clinical Observation

Background. Aortic isthmus retrograde blood flow in intrauterine children with growth delay and centralization of blood circulation in the late stages of placental dysfunction is associated with a high risk of perinatal death. Timely diagnosis of such condition is crucial to select further obstetric tactics and delivery time. Clinical case description. Growth delay and absent end-diastolic flow in umbilical artery and no A-wave in the venous duct were diagnosed in intrauterine child (gestational age — 36 weeks) at ultrasound study. Peripheral resistance indices in middle cerebral artery in the intrauterine child were lower than peripheral resistance indices in umbilical artery. Color Doppler imaging has revealed aortic isthmus retrograde blood flow. The woman was recommended delivery due to critical circulatory disorder in the intrauterine child. Female child was delivered via Caesarean section, child’s weight — 890 g, APGAR score — 3/4. The newborn girl died due to multi-organ failure within the first day.Conclusion. Revealing the retrograde blood flow in intrauterine child in the aortic isthmus throughout the entire ventricular diastole is an unfavorable prognostic sign of the terminal stage of cerebral blood flow disturbance associated with placental dysfunction.

CORRELATION OF LIPOPROTEIN(a) AND CORONARY ARTERY DISEASES

&lt;div&gt;&lt;p&gt;&lt;strong&gt;INTRODUCTION:&lt;/strong&gt; Cardiovascular diseases (CVD) continue to be one of the leading causes of mortality worldwide. While factors such as diabetes, sedentariness, psychostress, genetic predisposition, hypertension, smoking, and hyperlipidemia are well-known in the etiology of atherosclerosis (Ath) of coronary arteries. Recent studies have also identified high concentrations of lipoproteins (a) [Lp(a)] as a risk factor. In fact, high concentrations of Lp(a) above 30mg/dl (reference value-30mg/dl) have been found to be a risk factor for Ath, leading experts to develop medications aimed at reducing Lp(a) concentrations and preventing atherosclerotic manifestations. &lt;a href="https://eas-society.org/"&gt;&lt;em&gt;The European Atherosclerosis Society&lt;/em&gt;&lt;/a&gt; has also released clinical guidelines for testing and treating high concentrations of Lp(a) as part of the global assessment of cardiovascular risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;THE GOAL OF THE STUDY:&lt;/strong&gt; The goal of this study is to investigate the concentration of Lp(a) in patients with coronary disease and its connection to the presentation of atherosclerosis of the coronary arteries in patients with CVD compared to a control group of healthy individuals. Through this study, we hope to gain a better understanding of the role of Lp(a) in CVD and its potential as a target for prevention and treatment. By identifying and addressing risk factors like high Lp(a) concentrations, we can work towards reducing the global burden of CVD and improving health outcomes for individuals around the world.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;THE AIM OF THE STUDY:&lt;/strong&gt; The aim of this study is to determine the concentration of lipoprotein(a) in patients with coronary disease, its connectivity and role in the presentation of atherosclerosis of the coronary arteries in patients with CVD compared to the control group of healthy individuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;MATERIAL AND METHODS:&lt;/strong&gt; As working material, the blood taken from the vein of patients with coronary disease was used - N0=80, (with an identical average age of 55.70±6.00 years old, of which 35 were female while 45 were male. In the study, there was also a control group: N0=80 healthy volunteers (45 were male and 35 female) with the same age as the patients. Blood for analysis was taken at 8 o'clock in the morning, at room temperature of 19-24°C, every three months in a period of 12 months.&lt;/p&gt;&lt;p&gt;Echocardiography and EKG were also performed on all the patients with Toshiba SSH-140A machine, color Doppler probe 3.7Hz, sectorial type, taking into account as key parameters the thickness of the back wall of the left ventricle and the thickness of-Left ventricular internal diameter end diastole (LVPVd) and interventricular septal end diastole (IVSd&amp;gt;12 mm). Together with the examination of Lp(a) concentrations, the lipid profile was also analyzed. The analyzes were done at the Clinical Laboratory Institute at the University Clinical Center of the Faculty of Medicine – Skopje, North Macedonia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;STATISTICAL PROCESSING OF THE MATERIAL:&lt;/strong&gt; From the statistical methods, arithmetic mean value, standard deviation X±SD were used. The comparative statistics of the lipid parameters between the analyzed groups were analyzed with students ‘t’ dependent and independent samples according to the Mann-Whitney U-test and Wilcoxon - test. The results of the lipid fractions will be shown tabularly (see table 3) with the statistical program SPSS V26.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;RESULTS:&lt;/strong&gt; The obtained values of lipids (Col.Total, TG, HDL-ch, LDL-ch) and lipoprotein (a) in both groups are presented with mean values and standard deviation X-SD. Due to the fact that in the obtained results of Lp(a) in both sexes, in patients with coronary disease, we did not notice any significant difference, we will present them as common for both groups, with CVD with maximum values of 78.00-16,00 mg/dl while in the control group =15.20-4.30 mg/dl, with a statistically significant difference with p&amp;lt;0.000. The same difference was found from the obtained results of lipid concentrations between the two groups with p &amp;lt;0.0001 (as presented in the tables below).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;CONCLUSION:&lt;/strong&gt; The results obtained in the paper proved that high concentrations of Lp(a) &amp;gt; 30 mg/dl are risk factors for the occurrence of Ath of the coronary arteries and that these patients are at a 5-8 times higher risk for the development of Ath of coronary arteries, compared to individuals with normal Lp(a) values, therefore the treatment of high concentrations of Lp(a) should be started at the beginning of their appearance. In conclusion, we can suggest that the adequate treatment of high Lp(a) concentrations and the balancing of the lipid profile can apparently affect the prevention of atherosclerotic processes of the coronary arteries, therefore we prefer that in individuals with a history of CAD and those with coronary disease, the examination of Lp(a) and lipid profile should be one of the initial examinations during the management of patients with CAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Keywords: &lt;/strong&gt;Lipoprotein (a), atherosclerosis, Cardiovascular Arterial Diseases (CAD), lipid profile.&lt;/p&gt;&lt;/div&gt;

Association of Left Atrial Strain With Ischemic Stroke Risk in Older Adults

The risk of ischemic stroke is higher among patients with left atrial (LA) enlargement. Left atrial strain (LAε) and LA strain rate (LASR) may indicate LA dysfunction when LA volumes are still normal. The association of LAε with incident ischemic stroke in the general population is not well established. To investigate whether LAε and LASR are associated with new-onset ischemic stroke among older adults. The Cardiovascular Abnormalities and Brain Lesions study was conducted from September 29, 2005, to July 6, 2010, to investigate cardiovascular factors associated with subclinical cerebrovascular disease. A total of 806 participants in the Northern Manhattan Study who were aged 55 years or older without history of prior stroke or atrial fibrillation (AF) were included, and annual follow-up telephone interviews were completed May 22, 2022. Statistical analysis was performed from June through November 2022. Left atrial strain and LASR were assessed by speckle-tracking echocardiography. Global peak positive longitudinal LAε and positive longitudinal LASR during ventricular systole, global peak negative longitudinal LASR during early ventricular diastole, and global peak negative longitudinal LASR during LA contraction were measured. Brain magnetic resonance imaging was used to detect silent brain infarcts and white matter hyperintensities at baseline. Risk analysis with cause-specific Cox proportional hazards regression modeling was used to assess the association of positive longitudinal LAε and positive longitudinal LASR with incident ischemic stroke, adjusting for other stroke risk factors, including incident AF. The study included 806 participants (501 women [62.2%]) with a mean (SD) age of 71.0 (9.2) years; 119 participants (14.8%) were Black, 567 (70.3%) were Hispanic, and 105 (13.0%) were White. During a mean (SD) follow-up of 10.9 (3.7) years, new-onset ischemic stroke occurred in 53 participants (6.6%); incident AF was observed in 103 participants (12.8%). Compared with individuals who did not develop ischemic stroke, participants with ischemic stroke had lower positive longitudinal LAε and negative longitudinal LASR at baseline. In multivariable analysis, the lowest (ie, closest to zero) vs all other quintiles of positive longitudinal LAε (adjusted hazard ratio [HR], 3.12; 95% CI, 1.56-6.24) and negative longitudinal LASR during LA contraction (HR, 2.89; 95% CI, 1.44-5.80) were associated with incident ischemic stroke, independent of left ventricular global longitudinal strain and incident AF. Among participants with a normal LA size, the lowest vs all other quintiles of positive longitudinal LAε (HR, 4.64; 95% CI, 1.55-13.89) and negative longitudinal LASR during LA contraction (HR, 11.02; 95% CI 3.51-34.62) remained independently associated with incident ischemic stroke. This cohort study suggests that reduced positive longitudinal LAε and negative longitudinal LASR are independently associated with ischemic stroke in older adults. Assessment of LAε and LASR by speckle-tracking echocardiography may improve stroke risk stratification in elderly individuals.

Left atrial deformation and risk of transient ischemic attack and stroke in patients with paroxysmal atrial fibrillation.

Left atrial (LA) remodeling is closely related to the occurrence of cerebral stroke; however, the relationship between early-stage impaired deformability of the left atrium and stroke/transient ischemic attack (TIA) remains unclear. The aim of this study was to evaluate the changes in LA deformability and to assess its relationship with stroke/TIA events using speckle tracking echocardiography. A total of 365 patients with paroxysmal atrial fibrillation (non-stroke/TIA [n = 318]; stroke/TIA [n = 47]) underwent comprehensive echocardiography with speckle tracking imaging to calculate mean LA longitudinal strain and strain rate values from apical 4-chamber, 2-chamber, and 3-chamber views. The stroke/TIA group was older, had a greater proportion of males, and had lower LA strain rate during left ventricular early diastole (SRE), and the difference was statistically significant (P < .05). On univariate linear regression analysis, the following clinical and conventional echocardiographic parameters showed a significant linear correlation (P < .001) with SRE: E/A ratio; LA volume index (VI); body mass index; mean E/e'; left ventricular ejection fraction; age; and hypertension. Multiple linear regression analysis revealed a linear dependence between SRE and E/A ratio, LA VI, and body mass index. The regression equation was y = -1.430-0.394X1 + 0.012X2 + 0.019X3 (P < .001) (y, SRE; X1, E/A ratio; X2, LA VI; X3, body mass index). In multivariate logistic regression analyses, SRE and sex ratio were independent risk factors for stroke/TIA (SRE, odds ratio 2.945 [95% confidence interval 1.092-7.943]; P = .033; sex, odds ratio 0.462 [95% confidence interval 0.230-0.930]; P = .031). Among patients with paroxysmal atrial fibrillation, SRE reflected impaired deformability of the left atrium in the early stages and was associated with the risk of stroke/TIA.

Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests.

The rod-shaped adult cardiomyocyte (CM) harbors a unique architecture of its lateral surface with periodic crests, relying on the presence of subsarcolemmal mitochondria (SSM) with unknown role. Here, we investigated the development and functional role of CM crests during the postnatal period. We found in rodents that CM crest maturation occurs late between postnatal day 20 (P20) and P60 through both SSM biogenesis, swelling and crest-crest lateral interactions between adjacent CM, promoting tissue compaction. At the functional level, we showed that the P20-P60 period is dedicated to the improvement of relaxation. Interestingly, crest maturation specifically contributes to an atypical CM hypertrophy of its short axis, without myofibril addition, but relying on CM lateral stretching. Mechanistically, using constitutive and conditional CM-specific knock-out mice, we identified ephrin-B1, a lateral membrane stabilizer, as a molecular determinant of P20-P60 crest maturation, governing both the CM lateral stretch and the diastolic function, thus highly suggesting a link between crest maturity and diastole. Remarkably, while young adult CM-specific Efnb1 KO mice essentially exhibit an impairment of the ventricular diastole with preserved ejection fraction and exercise intolerance, they progressively switch toward systolic heart failure with 100% KO mice dying after 13 months, indicative of a critical role of CM-ephrin-B1 in the adult heart function. This study highlights the molecular determinants and the biological implication of a new late P20-P60 postnatal developmental stage of the heart in rodents during which, in part, ephrin-B1 specifically regulates the maturation of the CM surface crests and of the diastolic function.

Knockdown of histone deacetylase 9 attenuates sepsis-induced myocardial injury and inflammatory response.

Myocardial cell damage is associated with apoptosis and excessive inflammatory response in sepsis. Histone deacetylases (HDACs) are implicated in the progression of heart diseases. This study aims to explore the role of histone deacetylase 9 (HDAC9) in sepsis-induced myocardial injury. Lipopolysaccharide (LPS)-induced Sprague Dawley rats and cardiomyocyte line H9C2 were used as models in vivo and in vitro. The results showed that HDAC9 was significantly upregulated after LPS stimulation, and HDAC9 knockdown remarkably improved cardiac function, as evidenced by decreased left ventricular internal diameter end diastole (LVEDD) and left ventricular internal diameter end systole (LVESD), and increased fractional shortening (FS)% and ejection fraction (EF)%. In addition, HDAC9 silencing alleviated release of inflammatory cytokines (tumor necrosis factor-α (TNF-α), IL-6 and IL-1β) and cardiomyocyte apoptosis in vivo and in vitro. Furthermore, HDAC9 inhibition was proved to suppress nuclear factor-kappa B (NF-κB) activation with reducing the levels of p-IκBα and p-p65, and p65 nuclear translocation. Additionally, interaction between miR-214-3p and HDAC9 was determined through bioinformatics analysis, RT-qPCR, western blot and dual luciferase reporter assay. Our data revealed that miR-214-3p directly targeted the 3'UTR of HDAC9. Our findings demonstrate that HDAC9 suppression ameliorates LPS-induced cardiac dysfunction by inhibiting the NF-κB signaling pathway and presents a promising therapeutic agent for the treatment of LPS-stimulated myocardial injury.

The value of left atrial longitudinal strain in evaluating left atrial appendage spontaneous echo contrast in non-valvular atrial fibrillation.

Spontaneous echo contrast (SEC) observed in transesophageal echocardiography (TEE) is a reliable predictor of the risk of future ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Left atrial strain globally reflects atrial function, remodeling and distensibility. The left atrial appendage (LAA) is a myogenic remnant of the left atrium, which can actively relax and contract. The left atrial appendage (LAA) is an important part of releasing the pressure of the left atrium. The key role of the left atrium is to regulate the left ventricular filling pressure, act as a reservoir for pulmonary venous return during ventricular contraction, and act as a conduit, transferring blood to the Left ventricle during early ventricular diastole. The purpose of this study was to explore the relationship between left atrial function and left atrial appendage spontaneous echo contrast (LAASEC). A retrospective study of 338 patients with non-valvular AF was conducted. Two-dimensional speckle-tracking echocardiography provided the following metrics of LA strain: LA strain during the reservoir phase (LASr), LA strain during the conduit phase (LAScd). LA or LAA has the dense SEC of more than grade 3, which is defined as mud like change or pre thrombosis. Patients with level 3 SEC (n = 81) has lower LASr than those with lower grades of SEC (n = 257) (7.20 ± 3.70 vs. 17.48 ± 8.67, P < 0.001). Multivariate logistic regression model showed that the type of atrial fibrillation (persistent∼), increased heart rate, decreased LASr were independently associated with the dense LAASEC (OR (CI 95%), 5.558 (1.618-19.09), 1.016 (1.006-1.026) 0.002, 1.224 (1.085-1.381), both P < 0.01). Venn Diagram showed that lower CHADVASC2 score groups had dense SEC cases. Receiver operating characteristic (ROC) curve was used for analyzing results and selecting cut off values. The cut off point for LASr < 8.85% and CHADVASC2 score was >2 scores with sensitivity and specificity were 79% and 85%. Lower LASr is independently associated with the dense LAASEC in NVAF and has incremental values superior to clinical scores. The decrease of LASr may be a potential non-invasive parameter for evaluating the higher risk of LAA thrombosis.

Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure.

Heart failure is a chronic progressive condition that significantly affects the quality of life of patients with high hospitalization and mortality rates. Jiashen tablets (JST), a Chinese herbal formula, have been reported to be an effective treatment against heart failure, however the underlying mechanisms remain obscure. This study was designed to determine the effect of JST on the treatment of heart failure and delineate the underlying mechanisms by an untargeted metabolomics approach. The chronic heart failure model was established by the permanent ligation of the left anterior descending coronary artery in rats. The cardiac functions of rats, including left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), left ventricular internal diameter end diastole (LVIDd) and end systole (LVIDs), and interventricular septum thickness in diastole (IVSd) and in systole (IVSs), were measured by echocardiography. Biochemical analysis and histopathological examination were also performed to evaluate therapeutic effects of JST for treating heart failure. UHPLC-QTOF-MS/MS coupled with multivariate statistical analyses were applied for plasma metabolic profiling to identify biomarkers and potential mechanisms of JST in the treatment of heart failure. Jiashen tablets could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing rat LVEF and LVFS and decreasing LVIDd, LVIDs, IVSd, and IVSs. Results of biochemical analysis and histopathological examination revealed that JST could reduce the serum lactate dehydrogenase (LDH) activity and the level of NT-pro BNP, markers of heart failure and myocardial damage, and inhibit myocardial fibrosis. Furthermore, in metabolomics analysis, a total of 210 metabolites with significant differences were identified between heart failure rats and normal rats, among which 29 metabolites were significantly restored after JST treatment. These metabolites were primarily involved in tryptophan metabolism, branched-chain amino acid metabolism, fatty acids β-oxidation, and glycerophospholipid metabolism. The present study illustrated the therapeutic effect of JST for the treatment of heart failure and delineated the underlying mechanisms mainly relating to the regulation of amino acid metabolism and lipid metabolism in heart failure rats.

Cardiac cycle affects risky decision-making

This study investigates whether decision-making under uncertainty is influenced by the cardiac cycle. To test this hypothesis, we examined the influence of the cardiac cycle on an individual's decision-making process in a gambling experiment. Participants were asked to choose one option with a sure payout or uncertain option with varying degrees of winning probability, ambiguity, and monetary amounts. The onset of presentation of the options is timed to coincide with either cardiac ventricular systole or diastole. The results show that, for most participants, the risk aversion score was lower in the systole trial than in the diastole trial. Model-based exploratory analysis revealed that the higher propensity to take risks in the systole trial compared with that in the diastole trial could be captured better by the change in the gambling bias against the utility of the risky options, rather than by a change in risk attitude. The results provide evidence that the natural fluctuation of cardiac afferent signals can affect risky decision-making.

Alterations in diastolic function and cardiac geometry in children: a longitudinal study across the spectrum of dialysis and transplant.

Children with kidney failure have increased risk for cardiovascular morbidities before and after transplantation. Ejection fraction is often preserved, masking cardiac dysfunction until severe. Data on longitudinal changes in diastolic function and cardiac geometry are limited. A prospective study was conducted to investigate longitudinal changes in diastolic function and structure pre- and post-kidney transplant compared with healthy peers. Transplant recipients (n = 41) had echocardiograms pre-transplant, 1, 18, 30, and 42months post-transplant. The controls (n = 26) underwent one echocardiogram. Diastolic function and cardiac geometry were assessed by E/e' lateral, E/A, interventricular septal end diastole diameter, left ventricular internal end diastole diameter, left ventricular posterior wall end diastole diameter, and left atrial dimension. E/e' of patients remained worse than controls until 30months post-transplant, and E/A was impaired at all time points compared to the controls. Left ventricular geometry was abnormal in 46% pre-transplant and remained altered in 44.7%, 32.3%, 30.7%, and 27.2% at 1, 18, 30, and 42months post-transplant. Determinants of diastolic dysfunction included hemodialysis, uncontrolled hypertension, steroid exposure, and metabolic syndrome; abnormal geometry was associated with glomerular diagnosis, dialysis duration, obesity, steroids, and metabolic syndrome. Abnormal diastolic function and structure were associated with left ventricular hypertrophy. Diastolic dysfunction and geometry partially improve after transplant but remain abnormal in a subset of patients compared to healthy peers. Traditional indicators of systolic function are preserved. Modifiable risk factors include dialysis modality and duration, uncontrolled hypertension, corticosteroids, obesity, and metabolic syndrome. Attention to diastolic changes provides opportunity for early intervention. A higher resolution version of the Graphical abstract is available as Supplementary information.

Abstract 13216: Evaluation of Left Ventricular Flow Propagation Velocity From Multi-Dimensional Cardiac Imaging

Introduction: The propagation velocity (Vp) during the left ventricular (LV) early diastole has been proposed as a marker of the diastolic function. However, the measurement of Vp is limited to one-dimensional data from Color M-mode (CMM) echocardiography and does not consider the spatiotemporal variation of Vp. Methods: We introduce a new method to evaluate the LV diastolic flow propagation from multi-dimensional cardiac flow imaging. The proposed method estimates the local and instantaneous flow propagation velocity (V prop ) by fitting the first order wave equation to the velocity gradients with weighted least-squares. The proposed method was validated using the synthetic vortex ring flow data. The method was applied to the LV flow data acquired with two-dimensional phase-contrast magnetic resonance imaging (pc-MRI) and 4D flow MRI. Results: The V prop estimated from multi-dimensional data has about 50% less error than the V prop from one-dimensional data. Fig. 1(a) shows the waveforms of the mitral inflow velocity, the IVPD, and the propagation intensity (I prop ) during the LV diastole of a normal filling patient. During early diastole, the timing of peak flow propagation coincides with the peak intraventricular pressure difference. Fig. 1(b) presents the fields of the blood flow velocity, the V prop , and the relative pressure from the timeframes indicated using the dotted lines in the waveform plots. The flow propagation towards the apex is mainly located at the front of the inflow jet and downstream of the vortex ring formed near mitral valve tips. Conclusions: This study introduces a novel propagation velocity measurement method for multi-dimensional cardiac flow imaging and demonstrated the V prop ’s spatial distribution temporal evolution.

Overexpression of NR4A2 alleviates renal and myocardial injury in diabetes nephropathy rats through the HDAC11/SPRY1 pathway.

Diabetic nephropathy (DN) remains the most prevalent cause of end-stage renal disease. Nuclear receptor subfamily 4 group A member 2 (NR4A2) is a nuclear receptor with unique physiological characteristics. This study explored the molecular mechanism of NR4A2 in renal and cardiac functions of DN rats. A rat model of DN was established by intraperitoneal injection of streptozocin. NR4A2, histone deacetylase 11 (HDAC11), and sprouty 1 (SPRY1) expressions were detected. The fasting blood glucose (FBG), urinary albumin (UAlb), serum creatinine (Cr), and blood urea nitrogen (BUN) were determined. The pathological injury of renal and myocardial tissues was evaluated. The mitral early to late diastolic flow velocity ratio (E/A ratio), left ventricular ejection fraction (LVEF), left ventricular systolic function (LVSF), left ventricular internal dimension systole (LVIDs), and left ventricular internal diameter diastole (LVIDd) were tested, and the levels of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were examined. The enrichment of NR4A2 in HDAC11 promoter and enrichment of H3K27 acetylation in SPRY1 promoter were measured. NR4A2 and SPRY1 were downregulated while HDAC11 was upregulated in renal and myocardial tissues of DN rats. NR4A2 overexpression reduced FBG, UAlb, Cr, and BUN, alleviated pathological injury of renal and myocardial tissues, elevated the E/A ratio, LVEF, and LVFS, but reduced LVIDs, and decreased serum cTnI and CK-MB. NR4A2 depressed HDAC11 expression by binding to the HDAC11 promoter. HDAC11 repressed SPRY1 transcription by suppressing the H3K27ac level. HDAC11 overexpression or SPRY1 inhibition reversed the alleviating effect of NR4A2 overexpression on DN rats. NR4A2 was poorly expressed in DN rats. NR4A2 overexpression suppressed HDAC11 expression by binding to the HDAC11 promoter and enhanced SPRY1 transcription by enhancing H3K27 acetylation, thereby alleviating the renal and myocardial injury of DN rats.

Speckle tracking-derived left atrial strain rate – undervalued and useful predictor of adverse events

Abstract Background Strain rate reflects the rate of change of the distance between two points of the myocardium occurring in the cardiac cycle. It is a time-dependent parameter requiring higher temporal resolution than standard strain assessment. Because of this limitation, speckle tracking-derived left atrial (LA) strain rate analysis is of less interest in the literature. Purpose To analyze the prognostic value of LA strain rate during 2-years follow-up in patients with atrial fibrillation (AF). Methods The prospective study involved 80 patients with nonvalvular AF scheduled for elective electrical cardioversion (mean age 63.5±13 years, 60% male). All patients underwent echo before cardioversion and 24 hours after conversion to sinus rhythm. We analyzed standard echocardiographic parameters. Using the speckle-tracking method, we assessed LA strain rate during ventricular systole LA-SSR, in the early stage of ventricular diastole LA-ESR, and during atrial active pump phase LA-ASR. The last one is possible to measure only in the sinus rhythm. The analysis included 4-chamber and 2-chamber views. The clinical endpoint was predefined as AF recurrence. Results Median time of the current AF episode was 2.1 (IQR 0.5–5) months. Standard echo measurements revealed a median left ventricular ejection fraction of 55% (IQR 46–58) and the median of LA volume indexed to body surface area 42 ml/m2 (IQR 33–51). The successful cardioversion rate was 90%. During follow-up, we noticed AF recurrence in 49 (68%) patients. The median time-to-event was 2 (IQR 1 to 6.9) months. Receiver operating characteristic curve analysis revealed that LA-SSR &amp;lt;−0.73 s–1 (AUC=0.745; p=0.0004) and LA-ESR &amp;gt;−1 s–1 (AUC=0.703; p=0.0015) assessed during AF as well as LA-ESR &amp;gt;−0.88 s–1 (AUC=0.644; p=0.04) and LA-ASR &amp;gt;−1 s–1 (AUC=0.837; p&amp;lt;0.0001) measured in sinus rhythm were the optimal cut-off values for predicting AF recurrence. The figure presents Kaplan-Meier survival analysis for AF recurrence. Conclusions Speckle tracking-derived LA strain rate predicts the recurrence of AF after successful electrical cardioversion. Funding Acknowledgement Type of funding sources: None.

Evaluation of the pulmonary vein ostia during the cardiac cycle using electrocardiography-gated cardiac computed tomography in cats.

Several studies in humans have provided detailed descriptions of the anatomy of the pulmonary veins (PVs) and their ostia for the implementation of thoracic interventions, such as radiofrequency ablation, for patients with atrial fibrillation. These studies have shown that electrocardiography (ECG)-gated multidetector computed tomography (MDCT) can evaluate the dimensional variations in the PVs or ostium according to the cardiac cycle. However, few studies have examined the PVs or ostia using MDCT in veterinary medicine. Therefore, this study investigated the variation in the diameter of the PV ostium in cats during the cardiac cycle using ECG-gated MDCT and determined the correlation between the size of the heart or left atrium (LA) and diameter of the PV ostium. This study included six cats, including five normal animals and one cat with hypertrophic cardiomyopathy. The PVs were found to drain into the LA via three ostia, i.e., the right cranial ostium, left cranial ostium, and caudodorsal ostium. Moreover, a diametric variation was observed in all PV ostia according to the cardiac cycle phase on ECG-gated MDCT: the maximal diameter was observed at the end of ventricular systole, and the minimal diameter was observed at the end of ventricular diastole for each PV ostium. There were no significant correlations between the heart or LA size and maximal or minimal diameter of each of the three PV ostia (p > 0.05); however, the enlargement of each PV ostium at the end of ventricular systole differed significantly from that at the end of ventricular diastole. This study suggested the clinical feasibility of ECG-gated MDCT in providing more detailed anatomical information about the PVs, including the dimensional changes during the cardiac cycle in cats. Based on this study, knowledge of the variations in the PV ostium offers interesting avenues for research into the effect of PV function. Furthermore, ECG-gated MDCT could allow for greater clinical application of interventional procedures in animals with various cardiac diseases.

Machine learning and bioinformatics to identify 8 autophagy-related biomarkers and construct gene regulatory networks in dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a condition of impaired ventricular remodeling and systolic diastole that is often complicated by arrhythmias and heart failure with a poor prognosis. This study attempted to identify autophagy-related genes (ARGs) with diagnostic biomarkers of DCM using machine learning and bioinformatics approaches. Differential analysis of whole gene microarray data of DCM from the Gene Expression Omnibus (GEO) database was performed using the NetworkAnalyst 3.0 platform. Differentially expressed genes (DEGs) matching (|log2FoldChange ≥ 0.8, p value < 0.05|) were obtained in the GSE4172 dataset by merging ARGs from the autophagy gene libraries, HADb and HAMdb, to obtain autophagy-related differentially expressed genes (AR-DEGs) in DCM. The correlation analysis of AR-DEGs and their visualization were performed using R language. Gene Ontology (GO) enrichment analysis and combined multi-database pathway analysis were served by the Enrichr online enrichment analysis platform. We used machine learning to screen the diagnostic biomarkers of DCM. The transcription factors gene regulatory network was constructed by the JASPAR database of the NetworkAnalyst 3.0 platform. We also used the drug Signatures database (DSigDB) drug database of the Enrichr platform to screen the gene target drugs for DCM. Finally, we used the DisGeNET database to analyze the comorbidities associated with DCM. In the present study, we identified 23 AR-DEGs of DCM. Eight (PLEKHF1, HSPG2, HSF1, TRIM65, DICER1, VDAC1, BAD, TFEB) molecular markers of DCM were obtained by two machine learning algorithms. Transcription factors gene regulatory network was established. Finally, 10 gene-targeted drugs and complications for DCM were identified.

Multisensory integration of anticipated cardiac signals with visual targets affects their detection among multiple visual stimuli

Many studies have elucidated the multisensory processing of different exteroceptive signals (e.g., auditory-visual stimuli), but less is known about the multisensory integration of interoceptive signals with exteroceptive information. Here, we investigated the perceptual outcomes and electrophysiological brain mechanisms of cardio-visual integration by using participants’ electrocardiogram signals to control the color change of a visual target in dynamically changing displays. Reaction times increased when the target change coincided with strong cardiac signals concerning the state of cardiovascular arousal (i.e., presented at the end of ventricular systole), compared to when the target change occurred at a time when cardiac arousal was relatively low (i.e., presented at the end of ventricular diastole). Moreover, the concurrence of the target change and cardiac arousal signals modulated the event-related potentials and the beta power in an early period (~100 ms after stimulus onset), and decreased the N2pc and the beta lateralization in a later period (~200 ms after stimulus onset). Our results suggest that the multisensory integration of anticipated cardiac signals with a visual target negatively affects its detection among multiple visual stimuli, potentially by suppressing sensory processing and reducing attention toward the visual target. This finding highlights the role of cardiac information in visual processing and furthers our understanding of the brain dynamics underlying multisensory perception involving both interoception and exteroception.

Morphological importance of coronary ostia in equine.

The position of the coronary ostia was investigated in 70 segments of the aorta from young adult crossbred horses. After fixation with a 4% buffered aqueous formaldehyde solution and cautious dissection of the aortic bulb, the morphometric relationships between the coronary ostium and the aortic valvar elements were digitally analysed with the support of Image-Pro Plus® software. In horses, the left coronary ostium was near to the right valvular commissure in all cases (100%) analysed in this study. The left coronary ostium was at the level of the intercommissural line in 57.1% and below it in 42.9%. The right coronary ostium was near to the left valvular commissure in 58.6% (2.14 ± 0.32 cm) and close to the right valvular commissure in 41.4% (2.27 ± 0.40 cm). Concerning the intercommissural line, the right coronary ostia was at its level in 24.3% and below it in 75.7%. Accessory coronary ostia were observed in 8.6% of the specimens. In view of the results, it was possible to assume that the positions of the coronary ostia in equines tend towards a standard morphological disposition. Thus, perfusion of the left coronary artery occurs partly more frequently in ventricular systole and complete perfusion occurs less frequently in ventricular diastole. For the right coronary artery, perfusion is mostly complete in diastole and partially in ventricular systole.

Warm, but not hypoxic acclimation, prolongs ventricular diastole and decreases the protein level of Na+/Ca2+ exchanger to enhance cardiac thermal tolerance in European sea bass

One of the physiological mechanisms that can limit the fish's ability to face hypoxia or elevated temperature, is maximal cardiac performance. Yet, few studies have measured how cardiac electrical activity and associated calcium cycling proteins change with acclimation to those environmental stressors. To examine this, we acclimated European sea bass for 6 weeks to three experimental conditions: a seasonal average temperature in normoxia (16 °C; 100% air sat.), an elevated temperature in normoxia (25 °C; 100% air sat.) and a seasonal average temperature in hypoxia (16 °C; 50% air sat.). Following each acclimation, the electrocardiogram was measured to assess how acclimation affected the different phases of cardiac cycle, the maximal heart rate (fHmax) and cardiac thermal performance during an acute increase of temperature. Whereas warm acclimation prolonged especially the diastolic phase of the ventricular contraction, reduced the fHmax and increased the cardiac arrhythmia temperature (TARR), hypoxic acclimation was without effect on these functional indices. We measured the level of two key proteins involved with cellular relaxation of cardiomyocytes, i.e. sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and Na+/Ca2+ exchanger (NCX). Warm acclimation reduced protein level of both NCX and SERCA and hypoxic acclimation reduced SERCA protein levels without affecting NCX. The changes in ventricular NCX level correlated with the observed changes in diastole duration and fHmax as well as TARR. Our results shed new light on mechanisms of cardiac plasticity to environmental stressors and suggest that NCX might be involved with the observed functional changes, yet future studies should also measure its electrophysiological activity.

DeepStrain Evidence of Asymptomatic Left Ventricular Diastolic and Systolic Dysfunction in Young Adults With Cardiac Risk Factors.

PurposeTo evaluate if a fully-automatic deep learning method for myocardial strain analysis based on magnetic resonance imaging (MRI) cine images can detect asymptomatic dysfunction in young adults with cardiac risk factors.MethodsAn automated workflow termed DeepStrain was implemented using two U-Net models for segmentation and motion tracking. DeepStrain was trained and tested using short-axis cine-MRI images from healthy subjects and patients with cardiac disease. Subsequently, subjects aged 18–45 years were prospectively recruited and classified among age- and gender-matched groups: risk factor group (RFG) 1 including overweight without hypertension or type 2 diabetes; RFG2 including hypertension without type 2 diabetes, regardless of overweight; RFG3 including type 2 diabetes, regardless of overweight or hypertension. Subjects underwent cardiac short-axis cine-MRI image acquisition. Differences in DeepStrain-based left ventricular global circumferential and radial strain and strain rate among groups were evaluated.ResultsThe cohort consisted of 119 participants: 30 controls, 39 in RFG1, 30 in RFG2, and 20 in RFG3. Despite comparable (>0.05) left-ventricular mass, volumes, and ejection fraction, all groups (RFG1, RFG2, RFG3) showed signs of asymptomatic left ventricular diastolic and systolic dysfunction, evidenced by lower circumferential early-diastolic strain rate (<0.05, <0.001, <0.01), and lower septal circumferential end-systolic strain (<0.001, <0.05, <0.001) compared with controls. Multivariate linear regression showed that body surface area correlated negatively with all strain measures (<0.01), and mean arterial pressure correlated negatively with early-diastolic strain rate (<0.01).ConclusionDeepStrain fully-automatically provided evidence of asymptomatic left ventricular diastolic and systolic dysfunction in asymptomatic young adults with overweight, hypertension, and type 2 diabetes risk factors.