Association Between Left Ventricular Global Function Index and Outcomes in Patients With Dilated Cardiomyopathy

Purpose: Left ventricular global function index (LVGFI) assessed using cardiac magnetic resonance (CMR) seems promising in the prediction of clinical outcomes. However, the role of the LVGFI is uncertain in patients with heart failure (HF) with dilated cardiomyopathy (DCM). To describe the association of LVGFI and outcomes in patients with DCM, it was hypothesized that LVGFI is associated with decreased major adverse cardiac events (MACEs) in patients with DCM.Materials and Methods: This prospective cohort study was conducted from January 2015 to April 2020 in consecutive patients with DCM who underwent CMR. The association between outcomes and LVGFI was assessed using a multivariable model adjusted with confounders. LVGFI was the primary exposure variable. The long-term outcome was a composite endpoint, including death or heart transplantation.Results: A total of 334 patients (mean age: 55 years) were included in this study. The average of CMR-LVGFI was 16.53%. Over a median follow-up of 565 days, 43 patients reached the composite endpoint. Kaplan–Meier analysis revealed that patients with LVGFI lower than the cutoff values (15.73%) had a higher estimated cumulative incidence of the endpoint compared to those with LVGFI higher than the cutoff values (P = 0.0021). The hazard of MACEs decreased by 38% for each 1 SD increase in LVGFI (hazard ratio 0.62[95%CI 0.43–0.91]) and after adjustment by 46% (HR 0.54 [95%CI 0.32–0.89]). The association was consistent across subgroup analyses.Conclusion: In this study, an increase in CMR-LVGFI was associated with decreasing the long-term risk of MACEs with DCM after adjustment for traditional confounders.

Drosophila Nesprin-1 Isoforms Differentially Contribute to Muscle Function

Nesprin-1 is a large scaffold protein connecting nuclei to the actin cytoskeleton via its KASH and Calponin Homology domains, respectively. Nesprin-1 disconnection from nuclei results in altered muscle function and myonuclei mispositioning. Furthermore, Nesprin-1 mutations are associated with muscular pathologies such as Emery Dreifuss muscular dystrophy and arthrogryposis. Nesprin-1 was thus proposed to mainly contribute to muscle function by controlling nuclei position. However, Nesprin-1′s localisation at sarcomere’s Z-discs, its involvement in organelles’ subcellular localization, as well as the description of numerous isoforms presenting different combinations of Calponin Homology (CH) and KASH domains, suggest that the contribution of Nesprin-1 to muscle functions is more complex. Here, we investigate the roles of Nesprin-1/Msp300 isoforms in muscle function and subcellular organisation using Drosophila larvae as a model. Subsets of Msp300 isoform were down-regulated by muscle-specific RNAi expression and muscle global function and morphology were assessed. We show that nuclei anchoring in mature muscle and global muscle function are disconnected functions associated with different Msp300 isoforms. Our work further uncovers a new and unsuspected role of Msp300 in myofibril registration and nuclei peripheral displacement supported by Msp300 CH containing isoforms, a function performed by Desmin in mammals.

Problems of the mediation function of East Asian English variants for Russian communicants

Communicating with Chinese, Japanese, and Korean users in English is a challenge for Russians, even if they have a perfect command of English. This is due to the fact that while performing a global function and retaining local features, the English language, non-native to its users, has specific phonetic features revealed as an accent in oral speech, as well as certain graphic innovations, which aggravates translating proper names and culture-loaded words into Russian in a written form of communication. The challenges result from co-existence of several transliteration systems in these languages, non-traditional sound and letter correlations as compared with British and American Englishes, non-traditional translation correlations when transliterating from Roman to Cyrillic. Translation problems proper are complicated by lexico-semantic and pragmatic factors, which can be interpreted only on the cultural basis. These challenges make it necessary to integrate the World Englishes paradigm into the courses of English departments, as well as preparing special textbooks and reference sources.

Cardiac MRI Based Left Ventricular Global Function Index: Association with Disease Severity in Patients with ICD for Secondary Prevention

Left ventricular (LV) ejection fraction (LVEF) is the most widely used prognostic marker in cardiovascular diseases. LV global function index (LVGFI) is a novel marker which incorporates the total LV structure in the assessment of LV cardiac performance. We evaluated the prognostic significance of LVGFI, measured by cardiovascular magnetic resonance (CMR), in predicting mortality and ICD therapies in a real-world (ICD) population with secondary ICD prevention indication, to detect a high-risk group among these patients. In total, 105 patients with cardiac MRI prior to the ICD implantation were included (mean age 56 ± 16 years old; 76% male). Using the MRI data for each patient LVGFI was determined and a cut-off for the LVGFI value was calculated. Patients were followed up every four to six months in our or clinics in proximity. Data on the occurrence of heart failure symptoms and or mortality, as well as device therapies and other vital parameters, were collected. Follow up duration was 37 months in median. The mean LVGFI was 24.5%, the cut off value for LVGFI 13.5%. According to the LVGFI Index patient were divided into 2 groups, 86 patients in the group with the higher LVGFI und 19 patients in the lower group. The LVGFI correlates significantly with the LVEF (r = 0.642, p < 0.001). In Kaplan–Meier analysis, a lower LVGFI (<13.5%) was associated with a higher rate of mortality and rehospitalization (p = 0.002). In contrast, echocardiographic LVEF ≤ 33% was not associated with a higher rate of mortality or rehospitalization. Multivariate Cox-regression analysis revealed a lower LVGFI (p = 0.025, HR = 0.941; 95%-CI 0.89–0.99) and diabetes mellitus (p = 0.027, HR = 0.33; 95%-CI 0.13–0.88) as an independent predictor for mortality and rehospitalization. There was no association between the combined endpoint and the LVEFMRT, LVEFecho, NYHA > I, the initial device or a medication (each p = n.s.). Further, in Kaplan–Meier analysis no association was evident between the LVGFI and adequate ICD therapy (p = n.s.). In secondary prevention ICD patients reduced LVGFI was shown as an independent predictor for mortality and rehospitalization, but not for ICD therapies. We were able to identify a high-risk collective among these patients, but further investigation is needed to evaluate LVGFI compared to ejection fraction, especially in patients with an elevated risk for adverse cardiac events.

The odyssey to dethrone LV ejection fraction continues: the prognostic value of LV global function index in heart failure

Background Left Ventricular (LV) Global Function index (LVGFi) is a parameter that combines data from global systolic performance and volumetric anatomical information, measurable by non-contrast Cardiac Magnetic Resonance (CMR). We aimed to evaluate whether LVGFi predicts major cardiovascular outcomes and outperforms LV ejection fraction (LVEF) in Heart Failure (HF). Methods We conducted a retrospective single-centre study of consecutive patients with HF who were referred to and had a LVEF &lt;50% at CMR. Other than inadequate images for endocardial or epicardial border delineation, there were no exclusion criteria. LVEF was determined by 3D measurement. LVGFi was calculated as the LV stroke volume to the LV global volume ratio (Figure 1). The primary endpoint was a composite of time to all-cause death or HF hospitalization. Results The cohort was comprised of 433 HF patients (mean age 64±12 years, 74.1% male, ischaemic HF 53.1%, NYHA I-II 83.9%) with a mean LVEF of 33.5±10.0% and LVGFi of 22.8±7.4%. Over a median follow-up of 27 (17–37) months, 85 (19.6%) met the primary endpoint and 42 (9.7%) died. Patients with an event of the primary endpoint had markers of more severe HF, as noted by a reduced functional capacity (NYHA I-II: 63.5 vs. 89.0%; p&lt;0.001) and increased natriuretic peptides [NT-proBNP: 2664 (1022–27242) vs. 791 (337–7258); p&lt;0.001). Likewise, CMR showed higher LV volumes (e.g., LV end-diastolic volume index: 137±50 vs. 120±43mL/m2; p=0.001) and reduced LV performance indices, namely LVEF (29.2±10.6 vs 34.5±9.6%; p&lt;0.001) and LVGFi (19.8±7.4 vs 23.6±7.3%; p&lt;0.001). Both LVEF and LVGFi independently predicted the primary endpoint in multivariate analysis (separately imputed into a model adjusted for NYHA, NT-proBNP and creatinine). The LVEF model was more powerful than that of LVGFi. Similarly, LVGFi did not provide incremental prognostic information over LVEF in c-statistics analysis (0.653 vs. 0.622; p=0.645) (Figure 2). Conclusion While LVGFi independently predicted major outcomes in patients with HF and LVEF &lt;50%, it did not surpass LVEF. Our findings contrast to those demonstrating LVGFi as a powerful variable that outperforms LVEF in hypertrophic cardiomyopathy, cardiac amyloidosis, and healthy subjects at risk of developing structural heart disease. We hypothesize that LVGFi might be primarily useful in the prognostic stratification of patients with preserved LVEF. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Abstract P505: Rv Sarcomeres From Lv-hfref Patients With Low Papi Have Abnormal Rv Thick Filament Structure

Patients with left heart failure and reduced ejection fraction (HFrEF) have variable RV failure that, if present, drastically worsens outcomes. In a cohort of 21 HFrEF patients from two hospital sites, we have previously shown (Aslam et al, Eur J HF; 2020: volume 23, pages 339-341) that like global function, RV myocyte maximum calcium-activated myocyte tension (T max ) is quite variable (COV 27%). To determine if a relationship between RV myocyte function and indices of RV chamber function exists, we trained a random forest classifier based on 41 clinical variables, including hemodynamic, laboratory, and echocardiographic data, and queried the importance of each. This revealed that the most predictive model for reduced T max was based on the pulmonary artery pulsatility index (PAPi), an established clinical index of RV failure. To gain insight into potential mechanisms for depressed T max in HFrEF patients with a low PAPi, we obtained small angle x-ray diffraction patterns in 5 HFrEF patients with depressed PAPi and T max and compared this to 5 non-failing (NF) controls. The equatorial intensity ratio I(1,1)/I(1,0) was reduced in low T max RV muscle fibers vs. controls (0.250.06 vs. 0.180.02, P<0.0001), suggesting myosin heads are more associated with the thick filament backbone. In meridional reflections, we find a significant decrease in M3 band spacing (14.340.03 nm in NF vs. 14.300.01 nm in HFrEF; P=0.0013) suggesting more myosin heads are in the “OFF” configuration. The latter may underly tension reduction in RV myocytes from failing RV HFrEF patients. Ongoing studies will examine these structural changes in HFrEF patients with a broader range of PAPi and T max to test if this association applies. These findings focus attention on thick filament structural and configuration abnormalities as potential culprits underlying RV disease in HFrEF. Further studies using novel sarcomere enhancers will test if these changes can be remedied, and if so, in which patients.

Algorithms for quadratic forms over global function fields of odd characteristic

This paper presents an adaptation of recently developed algorithms for quadratic forms over number fields in [4] to global function fields of odd characteristics. First, we present algorithm for checking if a given non-degenerate quadratic form is isotropic or hyperbolic. Next we devise a method for computing the dimension of the anisotropic part of a quadratic form. Finally we present algorithms computing two field invariants: the level and the Pythagoras number.

Left ventricular global function index as a predictor of adverse cardiovascular events in patients with acute coronary syndrome

Aim To evaluate the prognostic significance of the left ventricular global function index (LV GFI) in patients with acute coronary syndrome (ACS) using echocardiography (EchoCG).Material and methods The LV GFI is an index that integrates LV cavity volumes, stroke volume, and myocardial volume. This study included 2169 patients with ACS (1340 (61.8%) men) aged 64.1±12.6 years from two observational multicenter studies, ORACLE I and ORACLE II. 1800 (83 %) cases were associated with increased concentrations of myocardial injury markers, including 826 (38.1 %) cases of ST segment elevation myocardial infarction (MI). The observation was started on the 10th day of clinical condition stabilization and lasted for one year. EchoCG was performed with evaluation of LV GFI, which was calculated as a ratio of LV stroke volume to LV global volume. The LV global volume was calculated as a sum of mean LV cavity volume (LV end-diastolic volume + LV end-systolic volume / 2) and LV myocardial volume.Results The main outcome of the study was all-cause death (n=193); recurrent coronary complications (n=253) were analyzed separately. The only EchoCG parameter indicating an adverse outcome during the one-year follow-up was a LV GFI decrease to below 22.6 % with a sensitivity of 72 % and a specificity of 60% (area under the curve, AUC=0.63). A LV GFI <22.6 % was an independent predictor of all-cause death (p=0.019) along with age (p=0.0001), history of MI (p=0.034), and presence of heart failure (HF) (p=0.044), diabetes mellitus (p=0.012), and peripheral atherosclerosis (p=0.001). The LV GFI <22.6 %, (p=0.044), heart rate upon discharge from the hospital (p=0.050), history of MI (p=0.006), presence of HF (p=0.014), and peripheral atherosclerosis (p=0.001) were also independent predictors for recurrent coronary complications. Decreased LV GFI was associated with the risk of fatal outcomes independent of the LV ejection fraction at baseline.Conclusion In patients with ACS, the left ventricular global function index is an independent predictor for all-cause death and recurrent coronary complications and may be used for risk stratification.