Isovolumetric Relaxation Time Research Articles

Role of fetal cardiac assessment in predicting adverse perinatal outcomes in preterm dichorionic twins

Aim: To investigate the role of the fetal modified myocardial performance index (Mod-MPI) and fetal cardiac output index measurement in predicting adverse perinatal outcomes among preterm dichorionic twins. Materials and Method: This prospective cohort study was conducted at the X Clinic and included 34 dichorionic twin fetuses born early preterm and 40 dichorionic twin fetuses born late preterm. The early preterm group was divided into two according to whether they were admitted to the neonatal intensive care unit (NICU). The groups' cardiac function and Mod-MPI measurements were compared regarding their predictive ability for adverse perinatal outcomes. Results: The Mod-MPI values were similar between the early and late preterm groups (p=0.144). The left ventricular cardiac output Z-score was lower in the preterm group (p=0.014). The Mod-MPI and left ventricular outflow tract-isovolumetric contraction and isovolumetric relaxation times were significantly higher among the newborns admitted to the NICU in the early preterm group (p=0.002, p=0.003, and p=0.001, respectively). Conclusion: Our study suggests that the Mod-MPI measurement can be used to predict adverse perinatal outcomes in dichorionic twin fetuses born in the early preterm period.

Pediatric Primary Raynaud's Phenomenon: A Comprehensive Cardiovascular Analysis.

Our aim in this study is to evaluate the cardiovascular findings of pediatric patients with primary Raynaud's phenomenon (RP) and to determine if there are any pathological findings. Our study included 42 pediatric patients aged between 7 and 18 who were diagnosed with primary RP and did not have any additional underlying structural vascular disease or secondary rheumatological conditions. The control group consisted of 30 healthy volunteers aged 7-18years, matched by age and sex, without any additional diseases. We evaluated demographic, clinical, and laboratory findings, echocardiographic and capillaroscopic features, as well as carotid intima-media thickness. Compared to the control group, pediatric patients with primary RP showed increased A wave velocity and E/E' ratio parameters in the left ventricle, indicating diastolic dysfunction of the heart. The isovolumetric relaxation time (IVRT) was prolonged in both the left and right ventricles, and the E/A ratio decreased in the left ventricle. The myocardial performance index (MPI), indicating both systolic and diastolic dysfunction, increased in both ventricles. Additionally, the aortic stiffness index, aortic elastic modulus (Ep), and left carotid intima-media thickness (CIMT) significantly increased, while distensibility decreased in pediatric patients with primary RP compared to the control group. The cardiovascular evaluation of pediatric patients with primary RP revealed that diastolic dysfunction is likely present in both the left and right heart. Additionally, based on the aorta and carotid intima measurements, it is suggested that pediatric patients with primary RP are at risk for developing atherosclerosis.

Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

A meta-analysis of left ventricular dysfunction in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine, presenting a considerable morbidity risk. Although evidence consistently indicates an elevated risk of ischemic heart disease among AS patients, debates persist regarding the likelihood of these patients developing left ventricular dysfunction (LVD). Our investigation aimed to determine whether individuals with AS face a greater risk of LVD compared to the general population. To accomplish this, we identified studies exploring LVD in AS patients across five major databases and Google Scholar. Initially, 431 studies were identified, of which 30 met the inclusion criteria, collectively involving 2933 participants. Results show that AS patients had: (1) poorer Ejection Fraction (EF) [mean difference (MD): -0.92% (95% CI: -1.25 to -0.59)], (2) impaired Early (E) and Late (atrial-A) ventricular filling velocity (E/A) ratio [MD: -0.10m/s (95% CI: -0.13 to -0.08)], (3) prolonged deceleration time (DT) [MD: 12.30ms (95% CI: 9.23-15.36)] and, (4) a longer mean isovolumetric relaxation time (IVRT) [MD: 8.14ms (95% CI: 6.58-9.70)] compared to controls. Though AS patients show increased risks of both systolic and diastolic LVD, we found no significant differences were observed in systolic blood pressure [MD: 0.32mmHg (95% Confidence Interval (CI): -2.09 to 2.73)] or diastolic blood pressure [MD: 0.30mmHg (95% CI: -0.40 to 1.01)] compared to the general population. This study reinforces AS patients' susceptibility to LVD without a notable difference in HTN risk.

Serial tissue Doppler imaging in the evaluation of bronchopulmonary dysplasia-associated pulmonary hypertension among extremely preterm infants: a prospective observational study.

To evaluate serial tissue Doppler cardiac imaging (TDI) in the evolution of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) among extremely preterm infants. Prospective observational study. Single-center, tertiary-level neonatal intensive care unit. Infant born <28 weeks gestation. Utility of TDI in the early diagnosis and prediction of BPD-PH and optimal timing for screening of BPD-PH. A total of 79 infants were included. Of them, 17 (23%) had BPD-PH. The mean gestational age was 25.9 ± 1.1 weeks, and mean birth weight was 830 ± 174 g. The BPD-PH group had a high incidence of hemodynamically significant patent ductus arteriosus (83% vs. 56%, p < 0.018), longer oxygen days (96.16 ± 68.09 vs. 59.35 ± 52.1, p < 0.008), and prolonged hospital stay (133.8 ± 45.9 vs. 106.5 ± 37.9 days, p < 0.005). The left ventricular eccentricity index (0.99 ± 0.1 vs. 1.1 ± 0.7, p < 0.01) and the ratio of acceleration time to right ventricular ejection time showed a statistically significant trend from 33 weeks (0.24 ± 0.05 vs. 0.28 ± 0.05, p < 0.05). At 33 weeks, the BPD-PH group showed prolonged isovolumetric contraction time (27.84 ± 5.5 vs. 22.77 ± 4, p < 0.001), prolonged isovolumetric relaxation time (40.3 ± 7.1 vs. 34.9 ± 5.3, p < 0.003), and abnormal myocardial performance index (0.39 ± 0.05 vs. 0.32 ± 0.03, p < 0.001). These differences persisted at 36 weeks after conceptional gestational age. TDI parameters are sensitive in the early evolution of BPD-PH. Diagnostic accuracy can be increased by combining the TDI parameters with conventional echocardiographic parameters. BPD-PH can be recognizable as early as 33-34 weeks of gestation.

A new Doppler index, cerebro-placental-uterine ratio, and fetal cardiac parameters in early onset preeclampsia.

Our aim was to investigate the significance of cerebro-placento-uterine ratio CPUR, a new Doppler index, and fetal cardiac parameters (Mod MPI, EFT) in early-onset preeclampsia (EOPE) and to examine whether these parameters are related to perinatal outcome. Forty participants diagnosed with EOPE (preeclampsia cases diagnosed before 34 weeks of gestation) and 40 healthy pregnant women were included in this study. Demographic data were recorded. Doppler parameters such as middle cerebral artery (MCA), umbilical artery (UA), and uterine artery (Ut-A), and left modified myocardial performance index (Mod-MPI) and epicardial fat thickness (EFT) were measured. Cerebroplacental ratio (CPR) was determined by dividing MCA pulsatility index (PI) by UA PI. CPUR was calculated as the ratio of CPR to mean UtA-PI (CPUR = CPR/UtA-PI). All parameters were compared between the EOPE and control groups. Correlation tests were used to examine the relationship between Doppler parameters and perinatal outcome. p values less than 0.05 were considered statistically significant. The pulsatility index of the middle cerebellar artery, CPUR and CPR values were statistically lower in the EOPE group than in the control group (p = 0.002; p = <0.001; p = <0.001; respectively). No statistical differences were found between groups for isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), ejection time (ET), left mod-MPI, EFT (p = 0.117; p = 0.093; p = 0.398; p = 0.882; p = 0.202, respectively). Umbilical artery Doppler pulsatility index (PI), mean uterine artery Doppler pulsatility index (PI), were higher in the EOPE group than in the control group (p = 0.006; and p = <0.001, respectively). The CPUR value for predicting EOPE was ≤1.3652 with 74. 4% sensitivity and 94.9% specificity. Positive correlations were found between CPUR, CPR, and some neonatal parameters. CPUR, a new index combining fetal and uterine Doppler indices, may add contribution to predict adverse perinatal outcome and EOPE.

Assessment of fetal cardiac functions in pregnant women with anemia: prospective, case-control study.

To compare the fetal cardiac functions between pregnant women with iron deficiency anemia (IDA) and healthy controls. This single-center, prospective, case-control study was conducted at a tertiary hospital. A total of 150 patients, including 50 patients with IDA and 100 healthy pregnant women at 30-34 weeks of gestation, were included in the study. Of the patients with anemia, 20 had mild anemia, 18 had moderate anemia, and 12 had severe anemia. Pulsed-wave Doppler, M-mode, and tissue Doppler imaging (TDI) were performed to evaluate fetal cardiac functions. The fetal cardiac score was calculated using the systolic, diastolic, and global hemodynamic function parameters. The myocardial performance index and isovolumetric relaxation time were significantly higher in the IDA group than the control group, while isovolumetric contraction time was similar. Among the tricuspid and mitral valve diastolic parameters, the E, A, and E/A values were significantly lower in the IDA group (p<0.001). Mitral and tricuspid annular plane systolic excursions (MAPSE and TAPSE, respectively) were significantly lower in the IDA group (p<0.001). The IDA group also had significantly lower values for the TDI parameters, mitral and tricuspid E', A', S', E'/A' and a significantly higher E/E' ratio (p<0.001). Upon examination of anemia subgroups, a significant decrease was observed in the tricuspid and mitral A, E, and E/A in those with severe anemia (p<0.001). M-mode Doppler analysis revealed significantly lower TAPSE and MAPSE in the patient group with severe anemia. According to the subgroup comparison of TDI findings, the patients with severe anemia had significantly lower tricuspid and mitral E', A', S' and E'/A' (p<0.001) values and a significantly higher E/E' ratio (p<0.001). The fetal cardiac score was significantly higher in the maternal IDA group compared to the control group. A significant negative correlation was found between maternal hemoglobin level and fetal cardiac score (p<0.001). There may be changes in the systolic and diastolic cardiac functions of the fetuses of pregnant women with IDA. This study showed an increased E/E' ratio in the fetuses of pregnant women with IDA, suggesting a decrease in fetal heart maturation. Within the IDA group, fetal cardiac functions were more affected in those with severe anemia. This article is protected by copyright. All rights reserved.

Epicardial fat thickness among neonates of diabetic mothers attending the neonatal intensive care unit at Fayoum University Hospital: a case control study

BackgroundUsing conventional echocardiography, this study aimed to evaluate the epicardial fat thickness (EFT) and its role in discriminating infants of diabetic mothers (IDMs) from those of non-diabetic mothers (INDMs) and to assess its prognostic role in IDMs. This case control study was conducted at the Neonatology and Cardiology Units of Pediatric Department, Fayoum University Hospital, Egypt, between February and September 2023. A total of 54 neonates were enrolled into three groups: 18 IDMs with well-controlled diabetes mellitus (DM), 18 IDMs with poorly controlled DM, and 18 INDMs.ResultsThe sensitivity, specificity, and cutoff of EFT were 100%, 100%, and 3.950 mm for detecting cases of IDMs and were 66.7%, 72.2%, and 5.100 mm for differentiating controlled from uncontrolled diabetic mothers, respectively. The interventricular septum in diastole (IVSd), interventricular septum in systole (IVSs), estimated pulmonary artery pressure (PAP), left ventricle (LV) Tei index, and isovolumetric relaxation time (IVRT) of LV all showed a positive correlation with EFT (r = 0.35, 0.31, 0.41, 0.34, and 0.39; P = 0.009, 0.025, 0.002, 0.01, and 0.003; respectively). There was a significant negative correlation between EFT and left ventricular internal dimensions in diastole (LVIDd) and left ventricular internal dimensions in systole (LVIDs) (r = − 0.44 and 0.42, P = 0.001 and 0.001). Regarding tissue Doppler, there was a significantly higher Tei index in group I cases compared to control (0.59 ± 0.10 vs. 0.49 ± 0.09, P < 0.001).ConclusionsThe EFT is higher in IDMs than in INDMs, with a positive correlation with birth weight, IVSd, IVSs, Tei index of mitral, IVRT, and ESPAP and a negative correlation with LVIDd and LVIDs. Neonatal EFT can be used as one of the helpful parameters to detect IDMs. Also, it may be used as one of the prognostic factors in IDMs as it is positively correlated with the diastolic function of the LV.

Evaluation of cardiac electrophysiological features in patients with premature adrenarche.

This study aimed to analyze the cardiac effects of hyperandrogenism in premature adrenarche (PA) and evaluate the risk of arrhythmia development. Fifty patients with PA and 50 healthy children from a pediatric endocrinology outpatient clinic were included in the study. The patients underwent echocardiography and electrocardiographic evaluations. Conventional echocardiography, tissue Doppler echocardiography, repolarization time, and repolarization dispersion time were evaluated. The median age in the PA and control groups was 7.91 years (5.83-9.25), 8.08 years (5.75-9.33), respectively. Thirty percent of patients in the PA group were male. While mitral early diastolic velocity deceleration time (DT), isovolumetric relaxation time (IRT), and E/e' ratio were significantly higher in the PA group than in the control group, mitral lateral annulus tissue Doppler early diastolic velocity was significantly lower (p=0.0001, 0.0001, 0.003, 0.0001). While P wave dispersion (PWD), Tpe, and QT-dispersion (QT-d) values were significantly higher in the PA group than in the control group, the P minimum value was significantly lower in the PA group (p=0.0001, 0.02, 0.004, and 0.0001, respectively). Early subclinical diastolic dysfunction was observed in the PA group. There was an increased risk of atrial arrhythmia with PWD and an increased risk of ventricular arrhythmia with increased Tpe and QT-d. There was a correlation between testosterone levels and diastolic function parameters. The increased risk of atrial arrhythmia is closely related to diastolic function.

Doppler echocardiography for surveillance of acute cardiac allograft rejection: a 28-year single-center experience.

Endomyocardial biopsies (EMB) are recommended for the detection of acute cardiac rejection (ACR) despite limited sensitivity. We report the long-term post-transplant results of Doppler echocardiography as a noninvasive alternative of routine EMB. Two cohorts of heart transplantation (HT) recipients were chronologically defined as follows: the Dual Monitoring Cohort (DMC) from January 1990 to December 1997 included patients who underwent routine EMB and Doppler echocardiography within 24 hours for ACR surveillance; and the "Echo-First Cohort" (EFC), including patients transplanted from January 1998 to December 2018 with Doppler echocardiography as first-line approach for ACR surveillance. Echocardiographic measurements of interest were collected: early diastolic (E) wave peak velocity; pressure half time (PHT) and isovolumetric relaxation time (IVRT). Post-transplant outcomes were reviewed and the Kaplan-Meier approach was used for survival estimates. Inter-operator variability for ultrasound measurements was investigated. Data were collected from medical records from January 2019 to December 2020. A total of 228 patients were included, 99 patients in the DMC and 129 in the EFC. Overall, 5-, 10- and 15-year survival rates were 65.4%, 55.5% and 44.1% respectively, without any significant difference between the two cohorts (log rank test, P=0.71). Echocardiography variables and EMB findings were associated with a mean area under the receiver operating characteristic curve (AUC-ROC) of 0.73 [95% confidence interval (CI): 0.54-0.91], 0.74 (95% CI: 0.54-0.94) and 0.75 (95% CI: 0.57-0.94) respectively for E wave, PHT and IVRT. IVRT and PHT were significantly decreased, and E wave significantly increased, in case of histologically proven ACR. Inter-operator variability was not significant for E wave and IVRT measurements (P=0.13 and 0.30 respectively). Doppler echocardiography as a first-line method for surveillance of ACR did not impair long-term results after HT. These findings suggest that this non-invasive approach might be a reasonable alternative to systematic EMB, limiting risk and improving the quality of life.

Assessment of fetal cardiac function in early fetal life: feasibility, reproducibility, and early fetal nomograms

BackgroundFetal cardiology has shown a rapid development in the last decades. Fetal echocardiography is not only used for the detection of structural anomalies but also to assess fetal cardiac function. Assessment of the fetal cardiac function is performed mostly at second and third trimester. The study of fetal cardiac function at the end of first timester has not been properly investigated and there is a lack of reference values at early gestational weeks. ObjectiveTo assess whether the measurement of time related parameters of cardiac function in the left ventricle of the fetal heart is feasible and reproducible at the end of the first trimester. If possible, we provide nomograms of these parameters from 11 to 13.6 gestational weeks. Study designWe conducted a prospective observational study from March to September 2022. The study was carried out in two hospitals (Hospital Universitari Dexeus, Barcelona and Hospital VITAHS 9 Octubre, Valencia). The scans were performed by 3 specialists in fetal medicine. Exclusion criteria were: fetal cardiac rhythm abnormalities, abnormal nuchal translucency, abnormal ductus venosus, fetal malformations, stillbirth, estimated fetal weight< 10 centile, diabetes and gestational hypertensive disorders. The cardiac function parameters studied in the left ventricle were: isovolumetric contraction time, isovolumetric relaxation time, ejection time, filling time, cycle time, myocardial performance index, ejection time fraction and filling time fraction. We study the feasibility and intra- and inter-observer reproducibility of this parameters using the interclass correlation coefficient (ICC). Nomograms were made and the percentiles of the values of the different parameters were calculated. Results409 cases were recruited but only 296 could be included in the statistical analysis once exclusion criteria were applied. The intra-observer reproducibility study was excellent (ICC>0.900) and the inter-observer reproducibility study was good (ICC>0.700). Data regression analysis showed that cycle time, filling time, isovolumetric contraction time and filling time fraction increased with gestational age, whereas ejection time fraction decreased with gestational age and myocardial performance index (mean 0.43±0.08), isovolumetric relaxation time (mean 0.04±0.01) and ejection time (mean 0.16±0.01) remained constant from 11 to 13 weeks. ConclusionsThe study of fetal cardiac function is feasible and reproducible at 11 to 13+6 gestational weeks. Nomograms of the studied parameters are provided.

Do Maternal Heart Diseases Affect Fetal Cardiac Functions?

To investigate whether fetal cardiac function is affected by underlying heart disease in pregnant women. A total of 100 pregnant women who were ≥34 gestational weeks were included in the study, 40 in the maternal heart disease (MHD) group diagnosed with heart disease and 60 in the control group. All cardiac diseases in pregnant women were diagnosed preconceptionally and categorized according to the New York Heart Association (NYHA) classification system. Fetal cardiac functions of study groups were evaluated by M-mode, color tissue Doppler imaging (c-TDI), and pulsed wave Doppler. Tricuspid annular plane systolic excursion and myocardial performance index (MPI) values were significantly higher and isovolumetric relaxation time was prolonged in the MHD group. The MPI value was found higher in MHD group with NYHA Class II compared to those with NYHA Class I. No significant change in any of the fetal tricuspid annular peak velocity values measured by c-TDI in the MHD group. There were no differences in fetal cardiac functions and perinatal outcomes between pregnant women with acquired and congenital heart diseases. Patients in NYHA Class II had lower birth weight, 1st and 5th minute APGAR scores, and higher neonatal intensive care unit admission rates. Underlying heart diseases in pregnant women can cause alterations in the systolic and diastolic function of the fetal heart. High fetal MPI values detected in cardiac patients may indicate that cardiac pathologies during pregnancy affect fetal cardiac globular myocardial function. Cardiac pathologies that progress with restricted physical activity may cause changes in fetal cardiac function and may be associated with adverse perinatal outcomes.

Evaluation of right ventricle functions in acute pulmonary thromboembolism using tissue doppler imaging

Aims: Right ventricular (RV) systolic and diastolic functions are impaired in a significant proportion of patients with acute pulmonary thromboembolism (PTE). In these cases, knowledge of RV function is of great importance both in the diagnosis and in the choice of treatment. Our aim was to evaluate RV systolic and diastolic functions by standard pulse Doppler and tissue Doppler imaging (TDI) in normotensive patients with PTE without hemodynamic disturbances. Methods: A total of 48 subjects, including 28 acute PTE patients (14 M, 14 F) with a mean age of 41 ± 13 years and 20 healthy subjects (10 M, 10 F) with a mean age of 40 ± 9 years, were included in our study. At the level of the tricuspid and mitral valve cusps, pulse Doppler echocardiography evaluated diastolic filling parameters. With the TDI technique, the diastolic function of the RV lateral wall and septum were analyzed in segments in the apical four-cavity image. Diastolic early and late velocities (e', a'), e'/a' ratio, e'dt, isovolumetric relaxation time (IVRT), systolic velocity (s'), and systolic duration (s' duration) were evaluated by TDI. Results: Among the RV standard Doppler parameters, a significant decrease in E velocity and E/A ratio and a significant increase in A velocity were observed compared to the control group (p=0.042; p=0.002; p=0.001, respectively). A non-significant prolongation in E’dt was detected. RV ejection fraction was significantly lower in PTE patients compared to the control group (51.1% vs. 69.7%) (p=0.001). TDI was used to look at the RV systolic function, and it was found that all segments had higher systolic (Sa-m) velocities than the control group. However, systolic velocities in patients with DHB in the RV were found to be lower in the annular regions and RV-free wall. Increased s' velocities were observed in annular regions and RV-free walls. However, no statistical significance was found in s' velocity values. Conclusion: RV systolic and diastolic functions may be impaired in normotensive patients with PTE without hemodynamic disturbances.

Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling.

Down syndrome (DS) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of DS, to quantify heart structure and function with echocardiography in 18-mo male Ts65Dn and wild-type (WT) mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of DS. The left ventricle was smaller in Ts65Dn versus WT, as well as the anterior wall thickness of the left ventricle during both diastole (LVAW_d; mm) and systole (LVAW_s; mm) as assessed by echocardiography. Other functional metrics were similar between groups including left ventricular area end systole (mm2), left ventricular area end diastole (mm2), left ventricular diameter end systole (mm), left ventricular diameter end diastole (mm), isovolumetric relaxation time (ms), mitral valve atrial peak velocity (mm/s), mitral valve early peak velocity (mm/s), ratio of atrial and early peak velocities (E/A), heart rate (beats/min), ejection fraction (%), and fractional shortening (%). Nicotinamide phosphoribosyltransferase (NAMPT) protein expression, NAD concentration, and tissue weight were lower in the left ventricle of Ts65Dn versus WT mice. Sirtuin 3 (SIRT3) protein expression and citrate synthase activity were not different between groups. Although cardiac function was generally preserved in male Ts65Dn, the altered heart size and bioenergetic disturbances may contribute to differences in aging for DS.

Effect of sodium-glucose type 2 cotransporter inhibitors on cardiac structure and function in patients with normal ejection fraction

Abstract Introduction Sodium-glucose cotransporter inhibitors (SGLT2i) have proven a reduction in cardiovascular events in diabetic patients with and without heart failure (HF), as well as in non-diabetic patients with heart failure with reduced and preserved ejection fraction (EF). The mechanisms underlying this benefit are not well known, with contradicting data on the changes that SGLT2i produce on cardiac function and structure. Methods Between October 2020 and October 2021, 31 diabetic patients without prior history of SGLT2i use with normal EF (&amp;gt;50%), glycated hemoglobin &amp;lt;6.5%, renal clearance rate of &amp;gt;60 ml/min/1.73 m2 and sinus rhythm were prospectively included. In all of them, SGLT2i were started. At inclusion and 6-months follow-up, different clinical, ECG, analytical and echocardiographic (standard, 3D and speckle tracking) variables were recorded. Results The average age of our population was 66.4 years (±8.4). 90% were male, 71% were hypertensive, 77.4% were dyslipidemic, 22.6% were obese and 87.1% were current or former smokers. 77.4% of patients had a history of ischemic heart disease, and 10% had vascular disease in other territories. At the time of inclusion, 80.6% of the population was treated with ACEI or ARB, 54.8% with beta-blockers, 29% with diuretics, and 93.5% with statins. After an average follow-up period of 6.6 months (±0.8), medication had to be withdrawn in 5 patients (in 3 of them due to repeated genital or urinary infections, and in 2 of them because of patient choice). An average reduction of 0.89 mm (±0.24, p = 0.001) in myocardial thickness was observed, as well as a reduction in the 3D-estimated left ventricle mass of 9.9 g/m2 (±4.5, p = 0.03), and in the E/é ratio of 1.4 (±4.5, p = 0.02). An increase in absolute left ventricle global longitudinal strain (LVGLS) of 0.74 (±0.35, p = 0.05) was observed, as well as an increase in isovolumetric relaxation time (IVRT) of 9.8 ms (±4.8, p = 0.05). An increase in LA strain and indexed volume was noted, although differences did not achieve statistical significance. No relevant differences in LV dimensions and volumes were observed, as well as in the evaluated RV parameters (picture 1). Conclusions It is necessary to understand the mechanism underlying the clinical benefit of these drugs. This will allow us to better understand its effect in patients with HF. Our data shows that the use of SGLT2i is associated with cardiac improvements, both structural (myocardial mass) and functional (IVRT, LVGLS, E/e'), in a population of patients with normal EF.

Effects of SGLT2 inhibition on cardiac remodeling and heart failure development in rats with aortic stenosis

Abstract Introduction Aortic stenosis prevalence has been increasing as population ages. Currently, no medical therapies influence the natural history of aortic stenosis. Sodium glucose co-transporter 2 inhibitors (SGLT2i) have reduced heart failure hospitalization and cardiovascular mortality in heart failure patients with both reduced and preserved ejection fraction. The aim of this study was to evaluate the effects of SGLT2 inhibitor empagliflozin (EMPA) on cardiac remodeling and heart failure development in aortic stenosis rats. Methods Eighteen weeks after supra-aortic banding surgery, male Wistar rats were divided in four groups: Sham (n=15); sham + EMPA (Sham-EMPA, n=16); aortic stenosis (AS, n=27); and aortic stenosis + EMPA (AS-EMPA, n=27). Empagliflozin (10 mg/kg/day) was added to rat chow for 8 weeks. Echocardiogram was performed to evaluate cardiac structure and function. Myocardial collagen content was quantified by histology; activity of antioxidant enzymes and enzymes involved in energy metabolism was assessed by spectrophotometry. Protein expression was quantified by Western blot, and matrix metalloproteinase (MMP) activity by zymography. Statistical analysis: ANOVA and Bonferroni or Kruskal-Wallis and Dunn (p&amp;lt;0.05). Results AS-EMPA group had a lower frequency of anatomopathological heart failure features, a lower left ventricular (LV) dilatation (LV diastolic diameter: Sham 8.39±0.57; Sham-EMPA 8.25±0.38; AS 9.80±0.53; AS-EMPA 9.08±0.87 mm; LV systolic diameter: Sham 4.24±0.68; Sham-EMPA 4.19±0.57; AS 5.72±0.74; AS-EMPA 5.09±1.08 mm) and LV mass (Sham 0.85±0.11; Sham-EMPA 0.82±0.07; AS 2.19±0.27; AS-EMPA 1.76±0.34 g), and better diastolic function (isovolumetric relaxation time: Sham 28.6±2.28; Sham-EMPA 29.8±3.04; AS 18.9±2.59; AS-EMPA 22.9±5.02 ms) than AS. Systolic function was impaired in both AS and AS-EMPA compared to their respective controls and did not differ between AS-EMPA and AS. AS and AS-EMPA had larger myocyte diameter, higher interleukin-6 protein expression and lower catalase activity than Sham and Sham-EMPA, respectively. AS and AS-EMPA groups had lower enzyme activity from energy metabolism than their respective controls. AS presented higher lipid hydroperoxide concentration, collagen III and p65 NF-kB protein expression, and lower glutathione peroxidase activity than Sham. AS-EMPA had higher collagen I expression and inactive MMP-2 than Sham-EMPA. AS-EMPA presented higher glutathione peroxidase and intermediary active MMP-2, and lower interstitial collagen fraction (Sham 2.68±0.59; Sham-EMPA 3.16±0.33; AS 5.68±0.97; AS-EMPA 3.55±0.70 %) than AS. Conclusion Empagliflozin improves cardiac remodeling, diastolic function and myocardial oxidative stress, and reduces heart failure feature frequency and interstitial collagen fraction in aortic stenosis rats.

Abstract 11310: T Helper 1 Lymphocytes Promote Diastolic Dysfunction and Fibrosis in a Non-Hypertensive Angiotensin II Mouse Model of Heart Failure

Introduction: Angiotensin (Ang) II induces cardiac fibrosis and diastolic dysfunction, also in absence of hypertension (HTN). We found that a non-HTN AngII infusion fails to induce dysfunction and fibrosis in T cell receptor α deficient mice ( Tcrα -/- , bereft of T cells). Hypothesis: Since T helper 1 (Th1) lymphocytes promote adverse remodeling in models of heart failure (HF), we hypothesized that Th1 cells are sufficient to induce diastolic dysfunction and fibrosis in a non-HTN AngII model. Methods: Naïve CD4+ cells were isolated from wild type (WT) mice lymph nodes (LNs) and spleens (MACS columns) and differentiated into Th1 cells over 7 days using plates coated with anti-CD3 antibody (5 μg/ml) plus IL-12 (10 ng/ml) and anti-IL-4 (1 μg/ml) and from day 4, IL-2 (20 ng/ml). Adoptive transfer (AT) of 10 7 Th1 cells/500 μl PBS, naïve CD4+ cells, or PBS alone was performed into Tcrα -/- mice (3-11 months old, N=8-16/group) implanted with AngII (0.2 μg/kg/day) osmotic pumps for 4 wks. AT was repeated two weeks later. LV dimensions, ejection fraction (EF), and diastolic function (isovolumetric relaxation time - IRT) were measured with Doppler echocardiography. LV end-diastolic pressure (EDP) and peak systolic pressure (PSP) were measured with a Millar catheter. Heart slides were stained with picrosirius red to measure interstitial fibrosis. Results: All groups had similar LV dimensions, EF, and PSP (not shown). AT of naïve CD4+ cells or PBS did not increase the IRT vs baseline (7.3±0.9 vs 7.6±0.6 and 9.9±0.7 vs 8.8±0.7 ms). AT of Th1 cells significantly increased the IRT (15.6±0.9 vs 9.0±0.7 ms, all p&lt;0.0001). EDP was significantly higher in Th1 mice (11.5±0.8 mmHg) vs naïve CD4+ mice (4.6±0.8 mmHg) or PBS (5.2±0.6 mmHg) (all p&lt;0.0001). Interstitial fibrosis in Th1 mice (1.4±0.2%) was significantly higher than in naïve CD4+ mice (0.7±0.1%) or PBS (0.8±0.1%) (all p&lt;0.001). Conclusions: Th1 cells are sufficient to induce diastolic dysfunction and fibrosis in a non-HTN AngII HF mouse model.

Abstract 18614: Growth Hormone Releasing Hormone Agonists Reverse the Cardiometabolic Heart Failure With Preserved Ejection Fraction Phenotype via the Hypoxia-Inducible Factor 1 Alpha

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) treatment is limited due in large part to lack of understanding of the underlying mechanisms involved. Recently, we showed that growth hormone-releasing hormone-agonist (GHRH-agonist) has cardioprotective effects in a cardiometabolic HFpEF model; however, the mechanism of these therapeutic effects is still unclear. Here, we hypothesize that the anti-HFpEF properties of GHRH-receptor activation are mediated by hypoxia-induced factor (HIF)-1α pathway. Methods: Wild-type (WT) and HIF-1α cardiomyocyte knockout (HIF-1α CM KO) mice received a high-fat diet (HFD) plus the nitric oxide synthase inhibitor (L-NAME) for 9 weeks. After 5 weeks of HFD+L-NAME regimen, animals receive daily injections of GHRH-agonist, MR-356, or placebo during a 4-week period. Control animals received no HFD+L-NAME or MR-356 treatment. Echocardiography, blood pressure, glucose tolerance test, and hemodynamic measurements were evaluated. Results: The HFD+L-NAME diet produced a HFpEF phenotype, which was reversed in mice with intact HIF-1α treated with MR-356 (Figure 1 A-E). In contrast, following cardiac-specific deletion of HIF-1α CM , MR-356 no longer reversed (A) the elevated isovolumetric relaxation time (IVRT), (B) increased E/E’ ratio and (C) reduced global longitudinal strain (GLS). EF was preserved (D) while the slope of the end-diastolic pressure-volume relationship (EDPVR, E) was increased in the placebo group and restored by MR-356 in WT mice but not HIF-1α CM KO mice. Figure 1F shows representative pressure-volume loops from WT placebo, HIF-1α CM treated with placebo or MR-356. Conclusions: Our findings show that cardiac-specific HIF-1α deletion blocks cardioprotective effects of MR-356 suggesting that HIF-1α is necessary for its anti-HFpEF effects.

Dapagliflozin Improved Cardiac Function and Structure in Diabetic Patients with Preserved Ejection Fraction: Results of a Single Centre, Observational Prospective Study.

Sodium-glucose cotransporter inhibitors (SGLT2i) have demonstrated a reduction in cardiovascular events in diabetes and heart failure (HF). The mechanisms underlying this benefit are not well known and data are contradictory. The purpose of this study is to analyse the effect of dapagliflozin on cardiac structure and function in patients with normal ejection fraction. Between October 2020 and October 2021, we consecutively included 31 diabetic patients without prior history of SGLT2i use. In all of them, dapagliflozin treatment was started. At inclusion and during six months of follow-up, different clinical, ECG, analytical, and echocardiographic (standard, 3D, and speckle tracking) variables were recorded. After a follow-up period of 6.6 months, an average reduction of 18 g (p = 0.028) in 3D-estimated left ventricle mass was observed. An increase in absolute left ventricle global longitudinal strain (LV-GLS) of 0.3 (p = 0.036) was observed, as well as an increase in isovolumetric relaxation time (IVRT) of 10.5 ms (p = 0.05). Moreover, dapagliflozin decreased the levels of plasma creatin-kinase (CK-MB) and atrial natriuretic peptide (ANP). In conclusion, our data show that the use of SGLT2i is associated with both structural (myocardial mass) and functional (IVRT, LV-GLS) cardiac improvements in a population of diabetic patients with normal ejection fraction.

The evaluation of fetal interventricular septum with M-mode and spectral tissue Doppler imaging in gestational diabetes mellitus: a case-control study.

To demonstrate possible functional changes in the frequently affected fetal interventricular septum (IVS) with spectral tissue Doppler imaging (TDI) and M-mode imaging to compare gestational diabetes mellitus (GDM) and control groups. A total of 63 pregnant women with GDM, 30 on diet (A1 GDM) and 33 on treated with insulin (A2 GDM), and 63 healthy pregnant women randomly selected and matched to the case group in the control group were included. The GDM fetuses had significantly thickened IVS, increased early diastole (E'), atrial contraction (A'), systole (S'), higher myocardial performance index (MPI'), prolonged isovolumetric relaxation time (IVRT'), shortened ejection time (ET'), and decreased septal annular plane systolic excursion (SAPSE) than the controls. The A2 GDM group fetuses had significantly thickened IVS, increased S' and shortened ET' than the A1 GDM group. In the GDM group, we found a significantly positive low correlation between glycated hemoglobin levels and maternal serum fasting glucose and one-hour postprandial glucose with fetal IVS thickness. We demonstrated a significantly negative low correlation between maternal serum one-hour postprandial glucose, glycated hemoglobin levels, and gestational weight gain with fetal IVS ET'. Fetal IVS diastolic and systolic functions were altered in the GDM group compared to controls, and systolic functions were altered in A2 GDM compared to A1 GDM. This may alert clinicians to possible cardiovascular diseases in the postnatal life, and early preventive strategies and long-term lifestyle changes may provide protection in fetuses with GDM.