Diastolic Strain Research Articles

Abstract 18021: Environmental Circadian Desynchronization and Metabolic Stress Drive Heart Failure With Preserved Ejection Fraction (HFpEF)

Background: The pathogenic mechanisms underlying HFpEF (Heart Failure with preserved Ejection Fraction), which accounts for 50% of heart failure, remain unclear. Elevated endoplasmic reticulum (ER) stress has been implicated in HFpEF. Circadian disruption (CD) as seen in shift workers has been associated with an excess risk for chronic age-related disorders, including cardiovascular disease. Currently, the role of CD in HFpEF is not known. Hypothesis: The dual 'hits' of chronic metabolic stress and circadian disruption lead to increased ER stress, impaired unfolded protein response (UPR), and adverse cardiac remodeling resulting in HFpEF. Methods: High fat diet (HFD) fed C57BL6 male mice were subjected to chronic shifted light-dark (LD) cycles mimicking shift work (Shift), with appropriate controls. Metabolic (glucose tolerance, insulin sensitivity, body fat) and cardiac function parameters (systolic and diastolic function by ECHO, MRI, and terminal PV-loops) were collected. Cardiac tissue was analyzed using qPCR, western blot, bulk RNA-seq, spatial transcriptomics, proteomics, and histology. For in vitro studies, Bmal1 was deleted in H9C2 cells using CRISPR/Cas9. Results: ‘HS’ mice (HFD & Shift) had the most insulin resistance, glucose intolerance, and obesity, compared to ‘HR’ (HFD & Regular LD), ‘CS’ (Normal Chow & Shift) and ‘CR’ (Chow and Regular LD) groups. ECHO and MRI revealed preserved EF in all groups, with diastolic impairment in both HS and HR (↑MV E/E’, ↓MV E/A, and ↓LV diastolic strain) groups, HS>HR. Only ‘HS’ mice showed ↓cardiac compliance (↑β in EDPVR) and ↑lung weight suggestive of HF consistent with HFpEF. Gene and protein expression revealed dysregulation of numerous UPR pathway molecules (Atf6, Chop, Bip, Perk, and others) in HS mice. Mechanistically, Bmal1 deletion in CMs resulted in similar dysregulation of UPR genes. HS mouse hearts showed increased fibrosis, and spatial transcriptomics displayed enrichment of ATF4-related pathways in CMs and activated fibroblasts. Conclusions: The dual hit of metabolic and circadian stress induces HFpEF, which cannot be recapitulated by only one stressor. Our results identify previously unrecognized roles of UPR perturbation in driving HFpEF under circadian and metabolic stress.

Clinical study of left ventricular structure and function in patients with Anderson-Fabry disease before and after enzyme replacement therapy.

Cardiac left ventricular hypertrophy (LVH) is the most common manifestation of heart involvement in Anderson-Fabry disease (AFD). Conventional cardiac imaging is not sensitive enough to detect early signs of LVH in AFD. It remains uncertain whether enzyme replacement therapy (ERT) can prevent LVH progression and improve myocardial function. This study aimed to assess the effectiveness of two-dimensional speckle tracking echocardiography (2D-STE) in early detection of cardiac involvement in AFD and monitoring the efficacy of agalsidase alfa and agalsidase beta therapy. Thirteen consecutive AFD patients and 12 healthy controls underwent standard transthoracic 2D, color Doppler, tissue Doppler echocardiography, and 2D strain analysis. Global longitudinal strain (GLS) and global circumferential strain (GCS) were measured. Diastolic strain rate (SR) was extracted. Compared to healthy subjects, AFD patients without LVH showed lower levels of GLS (p < 0.001) and SR (p = 0.01), while there was no difference in GCS (p = 0.82). Following treatment, apical circumferential strain (ACS) showed improvement (p = 0.01). In AFD patients without LVH, there was a decrease in global and segmental LS. Higher plasma Lyso-GL-3 concentrations were associated with elevated ACS values after ERT, indicating that ACS in AFD patients without LVH, albeit normal, is involved in early LV dysfunction.

Biventricular Dysfunction and Ventricular Interdependence in Patients With Pulmonary Hypertension: A 3.0-T Cardiac MRI Feature Tracking Study.

Pulmonary hypertension (PH) results in right ventricular (RV) dysfunction, subsequently leading to left ventricular (LV) impairment. The mechanism underlying ventricular interdependence is largely uninvestigated. To explore the biventricular dysfunction and the ventricular interdependence in PH patients. Retrospective. One hundred and seven PH patients (mean pulmonary artery pressure >20 mmHg) and 72 age- and sex-matched controls with cardiac magnetic resonance imaging (MRI) studies. 3.0 T/balanced steady-state free precession sequence. LV and RV ejection fractions (EF) and RV and LV radial, circumferential, and longitudinal strains were assessed using commercial software. Strains were compared between controls, PH patients with preserved RVEF (RVEF ≥40%, N = 48), and PH patients with reduced RVEF (RVEF <40%, N = 59). Chi-squared tests or Fisher's exact test, t tests or Mann-Whitney U test, one-way ANOVA with Bonferroni's post hoc correction or Kruskal-Wallis test, Pearson or Spearman correlation, and multivariable linear regression analysis. A two-tailed P < 0.05 was deemed statistically significant. RV strain decreased sequentially from controls, through PH with preserved RVEF, to PH with reduced RVEF. PH patients with reduced RVEF had significantly lower LV strain, especially septal strain, and LV peak diastolic strain rate compared with both controls and PH patients with preserved RVEF. Multivariable analyses showed that RVEF was independently correlated with LV strain; furthermore, independent of RVEF, RV strain was significantly correlated with LV strain (LVGRS: β = 0.416; LVGCS: β = -0.371; LVGLS: β = 0.283). Subclinical impairment of RV function was found in PH with preserved RVEF. LV strain was impaired when RV was dysfunctional, which was associated with worsening RV strain. Therefore, while focusing on improving RV function, LV dysfunction in PH patients should also be monitored and treated early in order to slow the progression of the disease. 3 TECHNICAL EFFICACY: Stage 3.

Echocardiographic multiparameter assessment for patients with heart failure with preserved ejection fraction and atrial fibrillation.

We aimed to assess the echocardiographic parameters of cardiac structure and function in patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). Thirty-seven HFpEF patients with AF were selected, while 38 patients with simple HFpEF in the same period were selected as controls. Three-dimensional speckle-tracking echocardiography was performed on both groups and the parameters were compared. The early diastolic longitudinal peak strain rates [early diastolic longitudinal strain rate (LSRE), early diastolic circumferential strain rate (CSRE), early diastolic radial strain rate (RSRE) and early diastolic rotational strain rate (RotRE)], late diastolic longitudinal peak strain rates (LSRA, CSRA, RSRA and RotRA) and untwisting parameters [untwisting rate during isovolumic relaxation time (UTRIVR) and early peak untwisting rate (UTRE)] were all negatively correlated with the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity ( E/E') (p < 0.01). The cardiac event-free survival rate of the simple HFpEF group (92.11%) was significantly higher than that of the HFpEF + AF group (81.08%) (p < 0.0001). UTRIVR had a more significant correlation with E/E' ratio than the other indicators and could serve as a sensitive indicator for evaluating the diastolic function of patients with HFpEF + AF.

Detection of Early Myocardial Dysfunction by Imaging Biomarkers in Cancer Patients Undergoing Photon Beam vs. Proton Beam Radiotherapy: A Prospective Study.

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) were women. The median (interquartile range) of the mean heart dose was lower in the PBT than the PhT group (47 [27-79] vs. 217 [120-596] cGy, respectively; p < 0.001). Ejection fraction did not change in either group. Only the PhT group had reduced systolic tissue Doppler velocities at 3 months. 2D-STE showed changes in endocardial and epicardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing PhT (global longitudinal SRe, pretreatment vs. end of treatment (p = 0.04); global circumferential SRe, pretreatment vs. at 3-month follow-up (p = 0.003); global radial SRe, pretreatment vs. at 3-month follow-up (p = 0.02) for endocardial values). Epicardial strain values decreased significantly only in patients treated with PhT. Patients in the PhT group had a significant decrease in epicardial global longitudinal systolic strain rate (GLSRs) (epicardial GLSRs, at baseline vs. at end of treatment [p = 0.009]) and in GCSRe and GRSRe (epicardial GCSRe, at baseline vs. at 3-month follow-up (p = 0.02); epicardial GRSRe, at baseline vs. at 3-month follow-up (p = 0.03)) during treatment and follow-up. No changes on 2D-STE were detected in the PBT group. 4. Conclusions: Patients who underwent PhT but not PBT had reduced tissue Doppler velocities and SRe values during follow-up, suggesting early myocardial relaxation abnormalities. PBT shows promise as a cardiac-sparing RT technology.

Evaluation of left ventricular diastolic function in patients with coronary microvascular dysfunction via cardiovascular magnetic resonance feature tracking.

Coronary microvascular dysfunction (CMD) has been suggested to be one of the pathologic mechanisms contributing to heart failure with preserved left ventricular ejection fraction (LVEF) and left ventricular (LV) diastolic dysfunction. We therefore aimed to evaluate LV diastolic function in patients with CMD using cardiovascular magnetic resonance feature tracking (CMR-FT). We prospectively enrolled 115 patients referred to cardiology clinics for chest pain assessment who subsequently underwent coronary computed tomography angiogram and stress perfusion CMR. CMD was defined as the presence of subendocardial inducible ischemia detected through visual assessment. LV diastolic function was evaluated using CMR-derived volume-time curves and CMR-FT parameters. The former included early peak filling rate (PFR) and time to PFR; the latter included LV global/regional peak longitudinal diastolic strain rate (LDSR), circumferential diastolic strain rate (CDSR), and radial diastolic strain rate (RDSR). A total of 92 patients with 1,312 segments were eventually included. Of these, 19 patients were classified as non-CMD (48.8±11.2 years; 63.2% male) and 73 as with CMD (52.3±11.9 years; 54.8% male). The LVEFs were similar and preserved in both groups (P=0.266). At the per-patient level, no differences were observed in PFR, time to PFR, or LV global diastolic strain rates between the two groups. At the per-segment level, 51% (665/1,312) of the myocardial segments were classified as CMD, whereas 49% (647/1,312) were classified as non-CMD. CMD segments showed significantly lower regional CDSR (P=0.019) and RDSR (P=0.006) compared with non-CMD segments. Despite normal LV ejection fraction in CMD patients, decreased LV diastolic function in CMD myocardial segments indicates early diastolic impairment.

Impact of body mass index on worsening of diastolic function and impairment of left atrial strain in the general female urban population: a subanalysis of the Berlin female risk evaluation echocardiography follow-up study.

The association of body mass index (BMI) with diastolic dysfunction (DD) is well described in the literature. However, there is conflicting evidence and long-term follow-up data regarding effects of BMI on preclinical DD and left atrial (LA) function are scarce, highlighting the importance of early detection tools, such as myocardial strain. The aim of our study was to prospectively analyze the impact of clinical and demographic parameters, especially of BMI, on worsening of diastolic function and left atrial strain (LAS) in an urban population of women with a low prevalence of cardiovascular risk factors. An extensive clinical and echocardiographic assessment comprising the analysis of phasic LAS using two-dimensional speckle-tracking echocardiography (2D STE) was performed in 258 participants of the Berlin Female Risk Evaluation (BEFRI) trial between October 2019 and December 2020 after a mean follow-up period of 6.8 years. We compared clinical and echocardiographic parameters stratifying women by BMI < or ≥25 kg/m2, and we analyzed the impact of demographic characteristics on the worsening of DD and LA mechanics in the longer-term follow-up using univariate and multivariate regression analyses. 248 women were suitable for echocardiographic analysis of LAS using 2D STE. After a mean follow-up time of 6.8 years, LA reservoir strain (LASr) and LA conduit strain (LAScd) were significantly reduced in participants with a BMI ≥25 kg/m2 compared with women with a BMI <25 kg/m2 at baseline (30 ± 8% vs. 38 ± 9%, p < 0.0001; -14 ± 7% vs. -22 ± 8%, p < 0.0001). 28% of the overweighted women presented a deterioration of diastolic function at the time of follow-up in contrast with only 7% of the group with a BMI <25 kg/m2 (p < 0.0001). BMI remained significantly associated with LAS reductions after adjustment for other risk factors in multivariate regression analyses. Overweight and obesity are related to impaired LAS and to a worsening of diastolic function after a long-term follow-up in a cohort of randomly selected women.

Relationship between saxagliptin use and left ventricular diastolic function assessed by cardiac MRI.

Type 2 diabetes mellitus (T2DM) increases the risk of major cardiovascular events. In SAVOR-TIMI53 trial, the excess heart failure (HF) hospitalization among patients with T2DM in the saxagliptin group remains poorly understood. Our aim was to evaluate left ventricular (LV) diastolic function after 6months of saxagliptin treatment using cardiac magnetic resonance imaging (CMR) in patients with T2DM. In this prospective study, 16 T2DM patients without HF were prescribed saxagliptin as part of routine guideline-directed management. CMR performed at baseline and 6months after initiation of saxagliptin treatment were evaluated in a blinded fashion. We assessed LV diastolic function by measuring LV peak filling rate with correction for end-diastolic volume (PFR/LVEDV), time to peak filling rate with correction for cardiac cycle (TPF/RR), and early diastolic strain rate parameters [global longitudinal diastolic strain rate (GLSR-E), global circumferential diastolic strain rate (GCSR-E)] by feature tracking (FT-CMR). Among the 16 patients (mean age of 59.9, 69% males, mean hemoglobin A1c 8.3%, mean left ventricular ejection fraction 57%), mean PFR was 314 ± 108ml/s at baseline and did not change over 6months (- 2.7, 95% CI - 35.6, 30.2, p = 0.86). There were also no significant changes in other diastolic parameters including PFR/EDV, TPF, TPF/RR, and GLSR-E and GCSR-E (all p > 0.50). In T2DM patients without HF receiving saxagliptin over 6months, there were no significant subclinical changes in LV diastolic function as assessed by CMR.

Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1week after STEMI. The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

Association Between Endothelial Dysfunction and Left Ventricular Diastolic Stiffness - Subanalysis of the Flow-Mediated Dilation Japan (FMD-J) Study.

Endothelial dysfunction and increased left ventricular (LV) stiffness are associated with the incidence of heart failure with preserved ejection fraction (HFpEF). This study evaluated the association between endothelial dysfunction and LV diastolic stiffness. Endothelial dysfunction evaluated by flow-medicated vasodilation (FMD) and the reactive hyperemia index (RHI), which reflects endothelial dysfunction in the microvasculature, was measured in 112 subjects with hypertension in the Flow-Mediated Dilation Japan (FMD-J) study. Using transthoracic echocardiography, LV diastolic stiffness was evaluated by measuring diastolic wall strain (DWS) in the LV posterior wall. In this cross-sectional study, associations among FMD, RHI, and DWS were investigated using multiple regression analyses. The mean (±SD) age of the subjects 65±9 years, and 63% were men. DWS was significantly associated with RHI, but not FMD, on multivariate linear regression analysis (β=0.39; P<0.0001). This association was preserved in subjects without LV hypertrophy (β=0.46; P<0.0001). A DWS ≤median, suggesting increased LV diastolic stiffness, was significantly associated with RHI on multivariate logistic regression analysis (odds ratio 20.58; 95% confidence interval 4.83-87.63; P<0.0001). The receiver operating characteristic curve presented a cut-off value of 2.21 for RHI, with a sensitivity of 77% and a specificity of 71%, for DWS ≤median. RHI, rather than FMD, was associated with DWS. Endothelial dysfunction in the microvasculature may be associated with increased LV diastolic stiffness.

Abstract P2008.1: Association Of Myocardial Stiffening With Impaired Relaxation In A Diabetic Murine Model Of Left Ventricular Diastolic Dysfunction

Introduction: Left ventricular diastolic dysfunction (LVDD) is often manifested by impaired relaxation and myocardial stiffening in the left ventricle (LV). While impairments in the function of myofilament regulatory proteins are known to deteriorate LV relaxation, the effects of passive myocardial stiffening on the relaxation of active forces remain unknown. Methods: A diabetic murine model of LVDD (db/db, n=5) and wild-type mice (WT, n=5) were used to study the association between tissue-level passive stiffness and organ-level relaxation. Early transmitral flow velocity to mitral annular tissue velocity ratio (E/e’), measured by Doppler imaging, was used to assess LV relaxation. Cardiac magnetic resonance imaging was performed using a 7T Bruker scanner to estimate diastolic strains via image registration. Mechanical testing was performed on harvested LV free wall (LVFW) specimens to measure passive stiffness. Results: LVDD was confirmed by a high septal E/e’ ratio (Fig. 1A). The db/db mice presented an increase in passive LVFW stiffness measured as the tangent to the circumferential stress-strain curve at 30% strain (Fig. 1B). A positive correlation was observed between passive stiffness and E/e’ (Fig. 1C). End-diastolic strain calculations (Fig. 1D) corroborated LV filling impairment indicating significant reductions in circumferential LV strains (Fig. 1E). Conclusion: Passive stiffening may impair LV filling by not only restraining the passive stretch of the myocardium at diastole but also by decelerating the active relaxation. Further integrated in-vivo and ex-vivo studies of LVDD can deconvolute the “active” and “passive” causes of impaired relaxation.

Pulmonary transit time as a marker of diastolic dysfunction in Takotsubo syndrome

To evaluate the pulmonary transit time (PTT) and its derived parameters using cardiac magnetic resonance imaging (CMRI) as markers of diastolic dysfunction in Takotsubo syndrome (TS) and its relationship with transthoracic echocardiography and CMRI parameters. Twenty-two patients with TS, who exhibited diastolic dysfunction as assessed by transthoracic echocardiography, were enrolled retrospectively and the PTT, pulmonary transit time index (PTTI), and pulmonary blood volume index (PBVI) were evaluated using first-pass CMRI. PTT was calculated as the number of cardiac cycles required for a bolus of contrast agent to move from the right ventricle (RV) to the left ventricle (LV), whereas PTTI represents the PTT interval corrected for the heart rate. Finally, PBVI was calculated as the product of PTTI, and RV stroke volume indexed for body surface area. Normal references of PTT, PTTI, and PBVI were evaluated in a cohort of 20 age- and sex-matched healthy controls. Compared with healthy subjects, TS patients showed significantly higher PTT, PTTI, and PBVI (p=0.0001, p=0.0001, and p=0.002, respectively). Using multivariable logistic regression, PBVI provided the best differentiation between TS and controls (AUC 0.84). PBVI was significantly associated with the index of diastolic dysfunction and left atrial strain parameters. In addition, PBVI demonstrated a significant correlation with global T2 mapping (r=0,520, p=0,019). PTT and the derived parameters, as assessed using first-pass CMRI, are potential tools for assessing LV diastolic dysfunction in patients with TS.

Myocardial deformation imaging by 2D speckle tracking echocardiography for assessment of diastolic dysfunction in murine cardiopathology

Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.

MRI detects increased aortic stiffening and myocardial dysfunction after TEVAR of blunt injury in young patients.

Background: Thoracic endovascular aortic repair (TEVAR) is a well-established technique for the management of blunt thoracic aortic injury (BTAI). Despite improvements in vascular imaging, graft material properties, and implant techniques, stent-graft deployment artificially induces aortic stiffening. This study aimed to evaluate the midterm effect of thoracic endovascular aortic repair after blunt thoracic aortic injury on aortic stiffness and cardiac function in young patients using cardiovascular magnetic resonance (CMR) imaging. Patients and methods: From all patients who underwent TEVAR for BTAI between 2009 and 2019 in a single institution, 10 patients with no other comorbidities affecting arterial stiffness were sex-, age-, height-, and body surface area-matched to 10 healthy controls. Comprehensive CMR examination was performed in all controls and patients. The mean follow-up period was 5.4±1.8 years; the mean age at the time of TEVAR was 30.3±8.7 years. Results: Four patients who underwent TEVAR developed arterial hypertension. 4D flow CMR-based analysis demonstrated higher global pulse wave velocity (PWV) in TEVAR patients than in controls (p=0.012). Segmental analysis showed a higher PWV in the descending and abdominal aorta. The indexed diameter of the ascending aorta was larger in TEVAR patients than in controls (p=0.007). The CINE acquisitions demonstrated increased left ventricular myocardial thickness (p<0.001). The 3D global diastolic strain rate and diastolic longitudinal velocity (e') decreased, and the A-wave velocity increased. Native myocardial T1 values were significantly higher in TEVAR patients (p=0.037). Conclusions: Young patients with TEVAR after BTAI are at an increased risk of developing vascular and myocardial dysfunction due to increased aortic stiffness. CMR follow-up allows for a comprehensive and radiation-free evaluation of vascular stiffness and associated myocardial changes, especially at the early and subclinical stages.

Normal Values and Reference Ranges for the Ratio of Transmitral Early Filling Velocity to Early Diastolic Strain Rate: The Copenhagen City Heart Study

The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has recently emerged as a measure of left ventricular filling pressure. Reference values are needed for this new parameter for it to be used clinically. Healthy participants from a prospective general population study, the 5th Copenhagen City Heart Study, were used to establish reference values for E/e'sr derived from two-dimensional speckle tracking echocardiography. The prevalence of abnormal E/e'sr was assessed in participants with cardiovascular risk factors or specific diseases. The population comprised 1,623 healthy participants (median age: 45, IQR: 32-56, 61% females). The upper reference limit for E/e'sr in the population was 79.6cm. Following multivariable adjustment, males exhibited significantly higher E/e'sr than females (upper reference limit for males: 83.7cm and for females: 76.5cm). For both sexes, E/e'sr increased in a curvilinear fashion with age such that the largest increases in E/e'sr were observed in participants >45years. In the entire CCHS5 population with E/e'sr available (n=3,902), increasing age, BMI, systolic blood pressure, male sex, eGFR, and diabetes were associated with E/e'sr (all p<0.05). Total cholesterol was associated with a less steep increase in E/e'sr. Abnormal E/e'sr was seldomly observed in participants with normal diastolic function but became more frequent in participants with increasing grades of diastolic dysfunction (normal, mild, moderate, severe (abnormal E/e'sr in normal, mild, moderate, and severe diastolic dysfunction; 4.4% vs. 20.0% vs. 16.2% vs. 55.6%). E/e'sr differ between sexes and is age dependent such that E/e'sr increases with advancing age. Therefore, we established sex- and age-stratified reference values for E/e'sr.

Is increased myocardial triglyceride content associated with early changes in left ventricular function? A 1H-MRS and MRI strain study.

Type 2 diabetes (T2D) and obesity induce left ventricular (LV) dysfunction. The underlying pathophysiological mechanisms remain unclear, but myocardial triglyceride content (MTGC) could be involved. This study aimed to determine which clinical and biological factors are associated with increased MTGC and to establish whether MTGC is associated with early changes in LV function. A retrospective study was conducted using five previous prospective cohorts, leading to 338 subjects studied, including 208 well-phenotyped healthy volunteers and 130 subjects living with T2D and/or obesity. All the subjects underwent proton magnetic resonance spectroscopy and feature tracking cardiac magnetic resonance imaging to measure myocardial strain. MTGC content increased with age, body mass index (BMI), waist circumference, T2D, obesity, hypertension, and dyslipidemia, but the only independent correlate found in multivariate analysis was BMI (p=0.01; R²=0.20). MTGC was correlated to LV diastolic dysfunction, notably with the global peak early diastolic circumferential strain rate (r=-0.17, p=0.003), the global peak late diastolic circumferential strain rate (r=0.40, p<0.0001) and global peak late diastolic longitudinal strain rate (r=0.24, p<0.0001). MTGC was also correlated to systolic dysfunction via end-systolic volume index (r=-0.34, p<0.0001) and stroke volume index (r=-0.31, p<0.0001), but not with longitudinal strain (r=0.009, p=0.88). Interestingly, the associations between MTGC and strain measures did not persist in multivariate analysis. Furthermore, MTGC was independently associated with LV end-systolic volume index (p=0.01, R²=0.29), LV end-diastolic volume index (p=0.04, R²=0.46), and LV mass (p=0.002, R²=0.58). Predicting MTGC remains a challenge in routine clinical practice, as only BMI independently correlates with increased MTGC. MTGC may play a role in LV dysfunction but does not appear to be involved in the development of subclinical strain abnormalities.

488-P: Subclinical Autonomic Neuropathy in Uncomplicated Type 2 Diabetes

Cardiac autonomic neuropathy (CAN), a common complication of type 2 diabetes (T2D), is often not detected until late in disease progression. Autonomic nervous system (ANS) dysfunction impairs control of heart rate (HR) and vascular dynamics, manifesting as decreased HR variability (HRV) and impaired blood pressure (BP) regulation. We hypothesized that ANS function is impaired in participants with uncomplicated T2D and correlates with cardiac measures. We measured HRV during cycled breathing and Valsalva and postural HR and BP on overweight physically inactive adults aged 22-70 years with (N=53) and without (N=56) T2D. HRV with cycled breathing and Valsalva was lower in participants with T2D (p=0.007 and 0.005, respectively). HRV with respiration was lower with age &amp;gt;50 years (p=0.0001). HRV with respiration correlated with increased age in T2D but not in overweight control participants. There were no significant changes in postural BP or HR with age &amp;gt;50 years or T2D. Significant correlations between ANS measures and cardiac function were only seen in those with T2D. Valsalva ratio was positively correlated with end-diastolic volume (Pearson’s r 0.58, p=0.02) and stroke volume (Pearson’s r 0.55, p=0.03). HRV with respiration was positively correlated with longitudinal, diastolic peak strain rate (SR) (Pearson’s r 0.68, p=0.007). Postural BP was positively correlated with circumferential and longitudinal, systolic peak SR (Pearson’s r =0.45 and 0.48 and p-value=0.05 and 0.04, respectively) and negatively correlated with radial and circumferential peak strain (Pearson’s r =-0.49 and -0.48 and p-value=0.03 and 0.03, respectively). These data suggest subclinical CAN associated with cardiac dysfunction is present in people with otherwise uncomplicated T2D and is exacerbated with age. Detecting CAN changes early may identify people at risk for cardiac disease and inform targeted intervention to restore cardiometabolic health in people with T2D. Disclosure A.Johnston: None. L.A.Abushamat: None. D.Enge: None. A.J.Barker: None. E.W.Clark: None. D.Rafferty: None. J.G.Regensteiner: None. J.E.B.Reusch: Advisory Panel; Medtronic. Funding American Diabetes Association (1-21-CMF-003 to L.A.A.); National Institutes of Health (T32DK120520-01A1); U.S. Department of Veterans Affairs (CX001532)

The impact of continuous positive airway pressure therapy on left atrial function assessed by 2D speckle tracking echocardiography in patients with obstructive sleep apnoea

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Obstructive sleep apnoea (OSA) is associated with left atrium (LA) remodelling and dysfunction, developing even before left ventricle (LV) hypertrophy and diastolic dysfunction. Two-dimensional speckle-tracking echocardiography (2D-STE) may help to detect subclinical LA dysfunction before irreversible cardiac changes. Purpose To evaluate changes of LA geometry and function after short term continuous positive airway pressure therapy (CPAP) for OSA using 2D-STE. Methods 47 obese patients aged between 18 to 65 years old were enrolled in the study. Control group (N=13) consisted of healthy subjects who either did not have OSA, or it was mild (apnea/hypopnea index (AHI) 5 – 14/ hour). OSA group (N=34) consisted of subjects with moderate or severe OSA (AHI ≥ 15/ hour). Transthoracic echocardiography and 2D STE analysis performed before and after 3 months of treatment with CPAP, for control group – at a baseline only. Statistical analyses were performed using the SPSS 27.0 software. The value of p&amp;lt;0.05 was considered as statistically significant. Results Control group was younger, had more female patients, and prevalence of arterial hypertension was lower compared to OSA group. All patients had preserved LV EF (&amp;gt;50 %) without significant differences between groups. OSA was related to more prevalent LV diastolic dysfunction (p = 0.023) and increased LV myocardial mass when indexed by height (46.11 (8.23) vs 38.96 (5.9) g/m 2.7, p = 0.007). OSA patients had significantly higher LA diameter (43.58 (8.19) vs 36.23 (3.08) mm, p &amp;lt;0.001), while LA volume did not differ even when indexed by height (p&amp;gt;0.05). LA reservoir strain was significantly lower in patients with OSA (26.56 (1.38) vs 31.01 (1.56) %, p&amp;lt;0.001) when compared to control group. After 3 months of CPAP treatment LA diameter, LA volume, LV MMi, LA conduit and contractile strain did not change , but prevalence of LV diastolic dysfunction decreased and LA reservoir strain improved. (Table 1). Conclusions Our study showed more prevalent LV diastolic dysfunction, increased LV myocardial mass indexed by height, together with reduced LA reservoir strain in OSA patients with preserved LV ejection fraction. Short term CPAP treatment significantly improved LV diastolic function and LA reservoir strain in OSA patients.

Predictive value of diastolic function assessed by CMR feature tracking in patients with suspected myocarditis and preserved left ventricular ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Reduced left ventricular systolic function is a well established predictor for outcome in Patients with myocarditis. However, the predictive role of diastolic function in patients with suspected myocarditis and preserved ejection fraction is unknown. Purpose Assess the predicative value of diastolic left ventricular function in patients with suspected myocarditis. Methods Late and early radial, circumferential and longitudinal diastolic strain rate was assessed as using CMR feature tracking in patients with clinically suspected myocarditis being referred for cardiac magnetic resonance imaging (CMR). The primary endpoint was defined as a composite of first major adverse cardiovascular events (MACE) including all-cause mortality, sustained ventricular tachycardia and hospitalization for heart failure. Results 755 consecutive patients with suspected myocarditis and referred for CMR (277, 37% female; mean age 48 ± 16years) were included. Of those late gadolinium enhancement (LGE) was present in 417 (55.2%). 416 had a preserved ejection fraction &amp;gt;50% (55.1%). Mace was documented in 123 patients (16.3%) during a median observational time of 3.77 years. After adjustment for LVEF, LGE extend, age, and gender early circumferential strain rate (HR=0.35 95% CI 0.16–0.77, p = 0.009), early longitudinal diastolic strain rate (HR=0.40 95% CI 0.17–0.96, p = 0.042) and late diastolic strain rate (HR=0.23 95% CI 0.07–0.74, p = 0.013) remained independent predictors of MACE. Conclusion CMR feature tracking diastolic strain rate is independently associated with outcome, beyond LVEF and LGE in patients with myocarditis, and might therefore contribute to improved risk stratification in this sclinical setting.

Radiotherapy-induced changes in right ventricular function in patients with early-stage breast cancer

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Finnish state research funding for university-level health research Background In breast cancer patient’s adjuvant RT nearly doubles cardiac mortality, and in some subgroups long-term cardiovascular mortality exceeds cancer mortality. The effects of RT on left ventricle are well established, but studies concerning right ventricular (RV) changes are sparse. Methods The study population consisted of 31 patients with early-stage left-sided breast cancer who had undergone adjuvant therapy using modern RT delivery techniques. Echocardiographic examinations including right ventricular (RV) strain analysis were performed prior to the RT, immediately after, as well as three and six years after the RT. In addition, the patients underwent cardiac magnetic resonance (CRM) imaging at six-year control. Results The mean RT dose to the RV free wall was 5.75±2.49 Gy. In echocardiography, basal early diastolic strain rate increased from 1.8±0.8 1/s to 2.3±0.9 1/s (p = 0.045), and the ratio of tricuspid inflow e and a-waves declined from 1.3±0.2 to 1.1±3.0 (p = 0.035), but there were no changes in global or regional strain or strain values in the six-year follow-up. In addition, In CMR imaging, the global circumferential strain values were associated with RV free wall RT dose (p = 0.005) with each mean Gy inducing 0.395% reduction in the circumferential strain [95% CI; −0.658, −0.120] whereas longitudinal strain was not associated with the RT dose. Conclusions Modern conformal breast cancer RT did not influence RV systolic function or result in clinically meaningful cardiac sequelae during six-year follow-up. Minor changes in RV diastolic function and the association between circumferential strain in CRM and the RT dose indicate that these parameters might be more sensitive in detecting RT-induced cardiac changes.