Cardiac Function Parameters Research Articles

Peripheral microvessel area better predicts the severity of coronary stenosis of acute myocardial infarction patients over pulse wave velocity

Microvascular obstruction (MVO) is linked with adverse clinical outcome in acute coronary syndrome (ACS) patients, therefore, early prediction of MVO with non-invasive peripheral microcirculation is crucial in facilitating optimal treatment. Current study aims to analyze the significance of opisthenar microvessel area (OMA, measured using optical coherence tomography, OCT) in predicting coronary stenosis (Gensini score, GS) and short-term cardiac recovery of ACS patients and the results were compared to those of arterial stiffness parameters (Pulse Wave Velocity, PWV; Ankle-Brachial Index; ABI). Results showed that cardiac functional parameters (e.g. ejection fraction, EF; fractional shortening, FS) and OMA were higher in normal/low risk (GS 0–≤ 20, n = 69) compared to medium/high risk patients (GS > 20, n = 44, P < 0.0001). Furthermore, OMA, EF or FS was negatively associated with the severity of coronary stenosis (P < 0.0001). In addition, OMA was negatively correlated with heart and liver damage parameters (e.g. creatine kinase, CK; creatine kinase muscle brain, CKmB; lactate dehydrogenase, LDH; hydroxybutyrate dehydrogenase, HDBH; aspartate aminotransferase, AST; alanine aminotransferase, ALT) or with inflammatory markers (neutrophil, neutrophil/lymphocyte ratio, NEU, NEU/LYM (NLR); systemic immune inflammation index, SII and system inflammation response index, SIRI), indicating clinical significance of OMA. Conversely, PWV and ABI were not associated with coronary stenosis or organ damage markers. Receiver Operator Characteristic (ROC) analysis showed high specificity and sensitivity of OMA for coronary stenosis (specificity 0.864 or sensitivity 0.87). In conclusion, OMA shows negative associations with the severity of coronary stenosis and adverse clinical parameters indicate that microcirculation measurement from opisthenar possesses prognostic value for severe ACS patients.

Abstract 4137180: Effectiveness of Exercise-based Interventions in the Prevention of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Patients: A Systematic Review and Network Meta-Analysis

Introduction: Breast cancer patients receiving anticancer therapy are at risk of developing cancer therapy-related cardiac dysfunction (CTRCD). While exercise has been shown to improve cardiorespiratory fitness in these patients, its effectiveness in preventing CTRCD remains unclear. Research Questions: How do exercise-based interventions affect CTRCD in breast cancer patients? Which exercise modality is most effective in preventing CTRCD? Goals: This network meta-analysis aimed to synthesize the available evidence on the effectiveness of exercise-based interventions based on cardiac function parameters and to identify the optimal exercise modality for preventing CTRCD. Methods: A comprehensive search was conducted in PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library from inception to March 4, 2024. Studies that used exercise interventions, either exercise alone or with other interventions, were included. Outcome measures included at least one cardiac function parameter such as left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS). Pairwise and network meta-analyses were performed using R software (v.4.3.3). Results: A total of 1149 participants from 14 RCTs were included. Compared to the usual care, exercise-based interventions significantly improved LVEF (MD=1.68; 95% CI=0.59-2.77; p＜0.05) and GLS (MD=1.40; 95% CI=0.59-2.21; p＜0.05). Based on the ranking probabilities, combined aerobic and resistance exercise was the most effective way to improve LVEF (4 studies, SUCRA: 96.46%), followed by cardiac rehabilitation (2 studies, SUCRA: 45.31%) and aerobic exercise (4 studies, SUCRA: 41.57%). In terms of improving GLS, combined aerobic and resistance exercise also ranked highest (3 studies, SUCRA: 87.77%). However, cardiac rehabilitation (2 studies, SUCRA: 46.70%) and aerobic exercise (1 study, SUCRA: 44.92%) were still less effective. Conclusion: This network meta-analysis provides low-certainty evidence for the potential efficacy of exercise-based interventions in preventing CTRCD, especially the combined aerobic and resistance training. Further rigorous studies are needed to confirm the effectiveness of exercise-based interventions in the prevention of CTRCD.

Abstract 4139191: ETX-258 - A GalOmic™ siRNA for the Treatment of Heart Failure Following Myocardial Infarction

Introduction: Heart failure with reduced ejection fraction (HFrEF) remains a significant clinical challenge, evidenced by high hospitalization rates and five-year mortality. Current treatments are limited by side effects, poor patient compliance, and the necessity for gradual drug titration. These challenges highlight the need for new therapies that are both safe and effective in targeting the structural remodeling pivotal to disease progression post-myocardial infarction (MI). e-therapeutics (ETX) uniquely combines computation and RNAi to discover life-transforming medicines. ETX’s RNAi platform, GalOmic™, enables generation of specific, potent, and long-acting siRNA therapies that effectively silence novel gene targets in hepatocytes. This highly specific mechanism of action limits unwanted side effects, positioning it as a promising approach to HFrEF treatment. Methods: Potent siRNAs against a hepatic target with cardioprotective potential were designed in silico. Candidate siRNAs were screened in vitro in HEK293 cells and in vivo in C57BL/6J mice to select the lead GalOmic™ siRNA, ETX-258. MI was induced by ligation of the left anterior descending artery in C57BL/6J mice after which ETX-258 was injected subcutaneously weekly for 6 weeks. Eplerenone, a mineralocorticoid receptor antagonist which is part of the current treatment regimen for HFrEF, was used as a comparator. Cardiac function was assessed by echocardiography at 2-, 4- and 6-weeks post-MI. Cardiac damage and structural remodeling were evaluated using circulating biomarkers of cardiac function and histological assessment. Results: ETX-258 was selected as a highly active siRNA for the treatment of heart failure with a long duration of action. Post-MI treatment with ETX-258 significantly improved key echocardiographic parameters of cardiac function, including ejection fraction and total cardiac output, achieving results comparable to eplerenone. Additionally, both structural cardiac parameters and markers of damage and remodeling showed significant improvements, reaching similar levels in both ETX-258 and eplerenone-treated mice. Conclusions: High unmet need remains for HFrEF patients despite existing therapies. These results highlight the potential of ETX-258 to improve cardiac function and pathogenic structural remodeling post-MI. This, paired with the long duration of action and favorable safety profile of GalOmic™ siRNAs, makes ETX-258 a promising candidate for further clinical development.

Association of biomarkers of cardiac remodeling, myocardial fibrosis and inflammation with parameters of heart function and structure in patients with arterial hypertension.

Early evaluation of cardiac remodeling may be useful in predicting heart failure in patients with arterial hypertension. The identification of biomarkers as useful clinical tools in this regard is ongoing. The aim of this study was to evaluate the association of selected cardiac biomarkers levels with parameters of cardiac structure and function in patients with arterial hypertension. Included in the study were patients with arterial hypertension with normal left ventricular ejection fraction (LV EF) and absence of signs of heart failure. The levels of selected biomarkers: NT-proBNP, sST2, Galectin-3, GDF-15, Cystatin C, TIMP-1 and ceruloplasmin were measured and assessed together with other biochemical and echocardiographic parameters. A total of 92 patients (61% men) mean age 61.5 years were included. Mean LV EF was 64.7% and mean LV mass index was 91.7 g/m2. NT-proBNP level correlated significantly with the parameters of LV diastolic function: velocity of E wave (r=0.377, P<0.002), and with E/A ratio, (r=0.455, P<0.0001), with E lat (r=-0.354, P=0.006), E/E' ratio, r=0.393, P<0.002, with ePAP (r=0.390, P=0.014), and with age (r=0.384, P<0.0001). Statistically significant correlations for GDF-15 were as follows: with age (r=0.426, P<0.0001) and left atrial diameter (LA) (r=0.401, P<0.0001), for Cystatin C there are statistically significant correlation with age (r=0.288, P=0.006) and LA (r=0.329, P=0.004). Only sST2 level correlated significantly with parameters of cardiac structure: with LV mass (r=0.290, P<0.01) and LV mass index (r=0.307, P=0.012) and with posterior wall thickness PW (r=0.380, P<0.001). No other observed variables including Galectin-3 and TIMP-1, correlated significantly with age or echocardiographic variables. In a comparison of patients with and without left ventricular hypertrophy, statistically significant differences were found only in LA (P<0.0001) and sST2 (P=0.004). In a multivariate logistic regression, sST2 and TIMP were independent predictors of left ventricular hypertrophy. NT-proBNP level as a biomarker of cardiac remodeling correlated with parameters of LV diastolic function in patients with arterial hypertension. Soluble ST2 correlated with parameters of cardiac structure. Biomarkers sST2 and TIMP-1 were associated with left ventricular hypertrophy.

Echocardiographic Assessment of Cardiac Remodeling According to Obesity Class

Evidence supports the existence of cardiac remodeling in obesity, but no standard diagnostic criteria has been proposed or validated.The objective of this study was to identify echocardiographic features of cardiac remodeling according to obesity class and assess the effect of non-surgical weight loss on cardiac structure and function.A total of 120 patients were divided according to their obesity class (Group 1: BMI 18.5-24.9; Group 2: 25-29.9; Group 3: 30-39.9; Group 4: >40) and underwent cross-sectional transthoracic echocardiography. Echocardiographic parameters of cardiac chamber quantification and function were compared between the 4 groups. Echocardiographic parameters were compared pre- and post-non-surgical weight loss in a subgroup of patients. Overall, there was an incremental increase in left ventricular (LV), left atrial (LA), and right ventricular dimensions, LV mass and LV stroke volume (all p<0.0001) across obesity classes. There was no significant difference in LV ejection fraction or right ventricular systolic function as assessed by tricuspid annular plane systolic excursion (TAPSE) but a significant decrease in global longitudinal strain (BMI 18.5-24.9: 22.8%±1.7%; BMI 25-29.9: 22.0%±1.4%; BMI 30-39.9: 20.8%±1.1%; BMI >40: 20.6%±1.3%, p<0.0001) and left atrial strain (BMI 18.5-24.9: 37.7%±2.3%; BMI 25-29.9: 32.8%±2.1%; BMI 30-39.9: 31.5%±1.8%; BMI >40: 29.0%±2.8%, p<0.0001). Allometric height-indexed LV and LA dimensions increased with increasing BMI class (p<0.0001). Echocardiographic parameters did not change significantly after non-surgical weight loss.In conclusion, echocardiographic features can be described according to obesity class. Allometric height indexation may better reflect cardiac remodeling in obesity in comparison to BSA indexation. Non-surgical weight loss was not associated with significant changes in cardiac chamber dimensions and function.

Sex differences of visceral fat with cardiac structure and function in type 2 diabetes: A cross-sectional study.

The aim of this study is to analyze the associations among fat distribution, left ventricular (LV) structure, and function in T2DM patients and further assess the sex differences among them. Two thousand and one hundred seven T2DM patients were enrolled to this study. Patients' height, weight, BMI, visceral fat area (VFA), baPWV, parameters of cardiac structure and function, and clinical biochemical indicators were measured and collected. There were significant differences between male and female T2DM patients in age, duration of diabetes, complication ratio of hypertension and dyslipidemia, smoking history, visceral fat, baPWV, and ventricular structure and function (p < 0.05). Compared with the Q1 group, female patients in the highest quartile (Q4) of VFA had a decreased LVEF and significantly increased baPWV (p < 0.05), whereas no such changes were found in males. The correlation analysis showed that LVEF in male patients was negatively correlated with hypertension history, using of CCBs, GLP-1RA, lipid-lowering medications, BMI, WC, WHR, FPG, FC-P, HbA1c, GA, HOMA-IR, Cr, and baPWV, while the LVEF in female patients was negatively correlated with VFA, VSR, VFA/BMI, VFA/H2, VFA/weight in females (p < 0.05). LVMI was positively associated with diabetes duration, age, hypertension history, WC, WHR, VFA, SFA, VFA/BMI, VFA/H2, VFA/weight, and baPWV in both males and females. Multivariable-adjusted linear regression analysis showed that VFA was independently associated with LVEF (β = - 0.096, p = 0.010), LVMI (β = 0.083, p = 0.038), and baPWV (β = 0.120, p = 0.003) in females. Values of VFA were independently associated with LVEF, LVMI, and baPWV in women, but not in men, in patients with T2DM.

1-Piperidine Propionic Acid Protects from Septic Shock Through Protease Receptor 2 Inhibition.

Sepsis is a complex disorder caused by a dysregulated host response to infection, with high levels of morbidity and mortality. Treatment aimed to modulate immune response and maintain vascular function is still one of the major clinical challenges. This study was designed to test the effect of the small molecule 1-Piperidine Propionic Acid (1-PPA) as molecular targeted agent to block protease-activated receptor 2 (PAR2), one of the major modulators of inflammatory response in LPS-induced experimental endotoxemia. In the THP-1 cell line, LPS-induced cytokine expression was inhibited by 1-PPA in a dose-dependent manner. In LPS-injected mice, treatment with 1-PPA was effective in reducing mortality and sepsis-related symptoms and improved cardiac function parameters. After 6 h from LPS injection, a significant decrease in IL-6, IL-1β, and IL-10 was observed in the lung tissue of 1-PPA-treated mice, compared to controls. In these mice, a significant decrease in vasoactive molecules, especially kininogen-1, was also observed, mainly in the liver. Histopathological analysis confirmed typical features of sepsis in different organs and these findings were markedly reduced in mice treated with 1-PPA. These data demonstrate the effectiveness of 1-PPA in protecting the whole organism from sepsis-induced damage.

Epicardial adipose tissue and subclinical alterations in cardiac structure and function in early adulthood

Abstract Background Epicardial adipose tissue (EAT) is the visceral fat depot surrounding the heart and coronary arteries and shares the same microcirculation with myocardium. Under normal physiologic conditions EAT contains important cardioprotective properties such as cushioning the heart against mechanical stress, thermoregulation of the myocardium in hypothermia as well as balancing myocardial fatty acid homeostasis. Higher accumulation of EAT has been reported to independently associate with deleterious alterations in cardiac structure and function. However, majority of previously addressed study results are derived from older study population and in presence of cardiovascular diseases. Data on the associations of EAT and cardiac echocardiograpghically derived structural and functional parameters in a young and middle-aged population without prevalent cardiovascular disease is scarce. Purpose We aimed to address this knowledge gap by investigating the associations of echocardiographically measured EAT thickness and possible adverse subclinical alteration in cardiac structure and function in a population cohort of young and middle-aged adults. Methods This study participants were examined as part of the ongoing multi-centre longitudinal cohort, focusing on cardiovascular risk factors from childhood through adulthood. EAT thickness was measured by manual delineation from parasternal long-axis echocardiograms at end systole. Transthoracic and Doppler echocardiograpghy was performed and data on cardiac structural and functional parameters were derived comprehensively in accordance with EAE/ASE guidelines. Results In this study population (N=1677, men=770, women=897 ; age range 34-49 years) mean EAT thickness was 4.0 mm in whole population. In multivariable regression analysis models adjusted for age, sex, waist circumference and systolic blood pressure, significant independent associations of EAT and left atrial dimension (P&amp;lt;.0001) and various measures of left ventricular (LV) wall thickness such as LV mean wall thickness (P&amp;lt;.001), LV relative wall thickness (P&amp;lt;.001) as well as LV posterior wall thickness (P&amp;lt;.001) were observed. We found no significant associations between EAT thickness and cardiac functional and hemodynamic parameters after covariate adjustments in multivariable analysis models. Conclusion The findings of this study highlight that larger EAT thickness is associated with subclinical alteration in cardiac wall thicknesses in young and middle-aged adults. However, we found no associations between EAT thickness and cardiac functional parameters, which is perhaps due to the high cardiac adaptation properties in our relatively young study population. Therefore, further follow-ups is required to address long-term probable alterations in cardiac hemodynamics when the participants are older.

Milk-derived extracellular vehicles alleviate heart failure with preserved ejection fraction by modulating gut microbiota

Abstract Background Accounting for around 50% of human heart failure, heart failure with preserved ejection fraction (HFpEF) is driven by complex and heterogeneous pathological factors, including gut microbiome dysbiosis. We have previously reported that milk-derived extracellular vesicles (mEVs) modulate the gut microbiota in inflammatory bowel disease. However, whether mEVs can affect gut microbiota and thereby alleviate HFpEF remains unexplored. Aims We aim to uncover potential therapeutic effects of mEVs on HFpEF and if so, the underlying mechanisms. Methods The HFpEF mouse model was generated by feeding C57/B6 mice on a high-fat diet and L-NAME for 15 weeks. Mouse feces samples were analyzed to detect the presence of gut dysbiosis in HFpEF. Mice received bovine mEVs through oral gavage. Heart function was assessed with echocardiography. Mouse feces and plasma were collected to analyze gut microbiota and metabolomics, respectively. Results Gut microbiota was disturbed in HFpEF mice. Oral administration of mEVs effectively attenuated heart failure which was evidenced by less bodyweight gain, reduction in cardiac hypertrophy and lung weight, and improvement in cardiac function parameters such as ratios of E/A (1.8 vs. 1.5, p&amp;lt;0.05) and E/E’ (40 vs. 27, p&amp;lt;0.05). Moreover, the increase in mouse blood pressure in HFpEF was also inhibited upon treatment (SBP 130mmHg vs. 100mmHg, DBP 90mmHg vs. 75mmHg, p&amp;lt;0.05). Mechanistically, we ruled out the possibility of direct action of mEVs on the heart as orally administered mEVs were only distributed in the intestine. On the other hand, mEVs restored gut microbiota by increasing the abundance of beneficial bacteria such as Lachnospiraceae. As a result, oral administration of mEVs elevated blood levels of Lachnospiraceae metabolite, butyric acid, a type of short-chain fatty acid. To confirm the butyric acid-mediated heart-protective effects of mEVs, we administered butyric acid to HFpEF mice. Strikingly, butyric acid largely reproduced the therapeutic effects of mEVs on HFpEF. Conclusions Oral administration of mEVs restores gut microbiota dysbiosis, thereby attenuating heart failure in HFpEF. mEVs may represent a new biological therapeutic for the treatment of HFpEF.

Association between GDF-15 levels and cardiac morphology and function in cardiac magnetic resonance imaging: insights from UK Biobank data analysis

Abstract Background/Introduction Growth Differentiation Factor-15 (GDF-15) has emerged as a biomarker associated with cardiovascular disease and adverse cardiac outcomes. Cardiac morphology and function, assessed through cardiac magnetic resonance imaging (CMR), are critical indicators of cardiovascular pathology. Understanding the relationship between GDF-15 levels and LV characteristics could provide valuable insights into cardiac pathophysiology and disease progression. Purpose This study aims to investigate the association between GDF-15 levels and cardiac morphology and function, utilizing data from the UK Biobank and CMR. By analyzing various CMR-derived parameters, including LV strain, myocardial mass, LV mass-to-volume ratio, ventricular and atrial volumes, we seek to elucidate the impact of GDF-15 on cardiac structure and function. Methods Data from the UK Biobank, including 2,264 participants, were analyzed. The median age of the analyzed participants was 55 years, with a median BMI of 26.0. Among the participants, 53% were females and 47% were males. CMR-derived variables related to cardiac morphology and function, along with GDF-15 levels, were examined. Multiple linear regression models were constructed to assess the association between GDF-15 levels and cardiac parameters, adjusting for age, sex, and other relevant covariates. Confidence intervals (CI) and p-values were calculated to determine the significance of observed associations. Results Analysis of the UK Biobank data revealed significant associations between GDF-15 levels and specific cardiac parameters (table1). Notably, GDF-15 levels were negatively associated with LV myocardial mass (LVM)(coefficient = -1.146, p = 0.0071), LV end-diastolic volume LVEDV)(coefficient = -3.321, p &amp;lt; 0.0001), LV end-systolic volume (coefficient = -1.876, p &amp;lt; 0.0001), as well as right atrial maximum volume (coefficient = -3.025, p &amp;lt; 0.0001) and minimum volume (coefficient = -1.858, p = 0.0003). In addition, LVM/LVEDV was positively associated with GDF-15 level (p&amp;lt;0.03). However, no significant associations were observed between GDF-15 levels and LV strain parameters, ejection fraction, or left atrial volumes. Conclusion This study provides evidence of a significant association between GDF-15 levels and selected parameters of cardiac morphology and function, as assessed by CMR in the UK Biobank population. These findings suggest a potential role of GDF-15 in modulating specific aspects of cardiac structure, function and left ventricle concentric remodeling warranting further investigation.GDF 15

Exaggerated blood pressure response to submaximal exercise must be considered relative to fitness: strong associations with hypertensive target organ damage

Abstract Exaggerated systolic blood pressure (SBP) during submaximal exercise is associated with increased cardiovascular (CV) risk. However, findings are mixed and new evidence indicates that cardiorespiratory fitness should be considered for proper clinical interpretation of exercise SBP responses. This study aimed to determine the relationship between SBP response to submaximal effort corrected for fitness and abnormalities of cardiac structure and function. Methods Each of 231 participants (age 54±12 years; 53% females) with controlled clinic BP, no evidence for ischemic heart disease, valvular heart disease or heart failure underwent cardiopulmonary exercise testing (Bruce protocol), resting and exercise echocardiography and 24h ABPM. Submaximal exercise SBP (measured at the 2nd stage of Bruce protocol) was corrected for two fitness variables: 1) peak VO2 and 2) maximal workload in METs (SBP/peakVO2 and SBP/METs). Results There were no, or weak, associations with exercise SBP and target organ damage. However, there was a progressive deterioration of cardiac function and structure parameters across the exercise SBP tertiles corrected for fitness (Table 1). Both SBP/peakVO2 and SBP/METs significantly correlated with left ventricular (LV) mass, LV diastolic and systolic, and left atrial parameters (Table 2). ROC analysis revealed good performance of corrected SBP response to submaximal exercise in detection of LV hypertrophy and diastolic dysfunction (AUC 0.792 and 0.808, and 0.771 and 0.802 for SBP/peakVO2 and SBP/METs, respectively; Figure). Conclusions Fitness-corrected SBP responses to submaximal exercise can identify more profound target organ damage with respect to cardiac function and structure even among patients with controlled clinic BP. Exaggerated BP response to exercise must be considered relative to fitness for proper clinical interpretation of BP responses to exercise testing.Figure

Improving exercise cardiac reserve assessment using a novel cardiopulmonary and echocardiography testing protocol (CPET-ESE) based on individualised exercise intensity domains

Abstract Background Functional exercise stress echocardiography (ESE) is used to quantify changes in cardiac reserve and can improve early cardiac dysfunction diagnosis and follow-up.[1.2] Current ESE protocols do not account for individual variations in fitness and heart rate response, leading to difficulties in defining normal reference values.[2,3] Physiologically defined exercise intensity domains could be implemented as part of combined cardiopulmonary and ESE testing (CPET-ESE) to address this problem. Purpose We propose that using exercise intensity domains as part of CPET-ESE will result in cardiac reserve values not influenced by individual cardiorespiratory fitness or physical activity (PA) levels. We also hypothesise by matching work-rates and heart rates (HR), respectively, cardiac reserve will be higher in those exercising at the higher exercise intensity domain. Methods A total of 45 healthy adults (mean age 43.8 ± 14.2, range 18-65 y) underwent a CPET followed by a CPET-ESE consisting of two 6-minute stages: 1. Moderate intensity (MOD) at 90% of the work-rate at the gas exchange threshold (GET) and 2. High intensity (HIGH) at 40% of the difference between GET and peak. Global left ventricular and right ventricular free wall (LV and RV) longitudinal strain (Sl), RV fractional area change (RV-FAC), peak LV and RV TDI derived systolic (S’) and diastolic velocities (E’) were measured at each step, including rest. HIGH steps were matched 1-to-n with MOD steps from other participants based on work-rate and HR, respectively. Questionnaire derived PA was classified as low, moderate, and high active. Cardiorespiratory fitness was measured as peak oxygen uptake relative to body mass (mL·kg-1·min-1). Results After adjusting for age and sex, neither higher PA nor peak VO2 were associated with higher cardiac function parameters at either intensity (Table 1). Higher peak VO2 was associated with higher work-rate for HIGH only, while higher PA was associated with lower HR for MOD only (interaction term p&amp;lt;0.05). When paired by matching HR and work-rate, respectively, HIGH was associated with higher cardiac function parameters compared to MOD (all except for LV-S’ and RV-FAC when HR matched, Table 2), despite those matched from HIGH being older, less physically active and having lower peak VO2 (p&amp;lt;0.05 for all). Conclusions Current ESE protocols, which define submaximal exercise intensity using arbitrary work-rate or HR targets,[3] do not account for the complex differences in exercise response between healthy individuals. Cardiac function augmentation during exercise is likely a response to VO2 kinetics and this is not accurately described by either HR or work-rate alone. We derived normal reference values for cardiac reserve from implementing physiologically defined exercise intensity domains within the combined CPET-ESE testing frameworks. These values could be more appropriately used when comparing diverse clinical populations using CPET-ESE.

Metabolic dysfunction-associated steatotic liver disease-associated fibrosis and cardiac dysfunction in patients with type 2 diabetes.

Metabolic dysfunction-associated steatotic liver disease (MASLD), particularly in the presence of liver fibrosis, increases the risk of cardiovascular morbidity and mortality, but the nature of the cardio-hepatic interaction in the context type 2 diabetes mellitus (T2DM) is not fully understood. To evaluate the changes in cardiac morphology and function in patients with T2DM and MASLD-associated liver fibrosis. T2DM patients with MASLD underwent a medical evaluation that included an assessment of lifestyle, anthropometric measurements, vital signs, an extensive laboratory panel, and a standard echocardiography. Liver fibrosis was evaluated using two scores [Fibrosis-4 (FIB4) and Non-alcoholic fatty liver disease-Fibrosis Score (NFS)], and subjects were classified as having advanced fibrosis, no fibrosis, or an indeterminate risk. The correlations between structural and functional cardiac parameters and markers of liver fibrosis were evaluated through bivariate and multiple regression analyses. Statistical significance was set at P < 0.05. Data from 267 T2DM-MASLD subjects with complete assessment was analyzed. Patients with scores indicating advanced fibrosis exhibited higher interventricular septum and left ventricular (LV) posterior wall thickness, atrial diameters, LV end-systolic volume, LV mass index (LVMi), and epicardial adipose tissue thickness (EATT). Their mean ejection fraction (EF) was significantly lower (49.19% ± 5.62% vs 50.87% ± 5.14% vs 52.00% ± 3.25%; P = 0.003), and a smaller proportion had an EF ≥ 50% (49.40% vs 68.90% vs 84.21%; P = 0.0017). Their total and mid LV wall motion score indexes were higher (P < 0.05). Additionally, they had markers of diastolic dysfunction, with a higher E/e' ratio [9.64 ± 4.10 vs 8.44 (2.43-26.33) vs 7.35 ± 2.62; P = 0.026], and over 70% had lateral e' values < 10 cm/second, though without significant differences between groups. In multiple regression analyses, FIB4 correlated with left atrium diameter (LAD; β = 0.044; P < 0.05), and NFS with both LAD (β = 0.039; P < 0.05) and right atrium diameter (β = 0.041; P < 0.01), Moreover, LVMi correlated positively with age and EATT (β = 1.997; P = 0.0008), and negatively with serum sex-hormone binding protein (SHBP) concentrations (β = -0.280; P = 0.004). SHBP also correlated negatively with LAD (β = -0.036; P < 0.05). T2DM patients with markers of MASLD-related liver fibrosis exhibit lower EF and present indicators of diastolic dysfunction and cardiac hypertrophy. Additionally, LVMi and LAD correlated negatively with serum SHBP concentrations.

Differential postnatal cardiovascular course of donor-recipient twins and associated pathophysiology-a cohort study.

Fetal echocardiography in twin to twin transfusion pregnancies treated with photocoagulation noted impaired cardiac function. Systematic information about cardiac structure or function and arterial distensibility after birth is not available. This study evaluated cardiovascular function and arterial dynamic properties in survivors of twin to twin transfusion syndrome. Eleven pairs of donor-recipient twins were compared with each other, and with 20 singletons of comparable gestational age. The twin cohort was born at 31.5±2 weeks gestational age; birthweights of donors-recipients were comparable (donors: 1358±421g vs recipients: 1617±460g, P=0.2). Significant inter-twin differences were noted for cardiac function parameters. Recipients had greater septal thickness (donors: 2.3±0.15 vs recipients: 2.7±0.36mm, P=0.01) and globularity (lower sphericity index [donors: 1.76±0.1 vs recipients: 1.62±0.12, P=0.009]). They also had lower cardiac function (tricuspid annular plane systolic excursion [donors: 4.6±0.5 vs recipients: 4.1±0.4mm, P=0.02) and right ventricular fractional area change [donors: 30±1 vs recipients: 27.7±1.3%, P=0.0001]). Comparing with singletons, differences were statistically more significant for recipients. Arterial distensibility however, was more affected in donors (higher arterial wall stiffness index [donors: 2.5±0.2 vs recipients: 2.2±0.2, P=0.008] and lower pulsatile diameter [donors: 51±5 vs recipients: 63±10 µm, P<0.0001). Comparing with singletons, the differences were statistically more significant for donors. Evaluation in the neonatal period noted that cardiac function and arterial distensibility is affected in TTTS twins. These cohorts will benefit from close postnatal follow up for resolution of cardiac and arterial impairments.

Effect of radiofrequency ablation on improving cardiac structure and function in patients with atrial fibrillation and functional mitral regurgitation

Objective: Exploring the effect of radiofrequency ablation treatment to restore sinus rhythm on the improvement of functional mitral regurgitation (FMR) and cardiac structure in patients with atrial fibrillation combined with moderate or severe FMR, compared with drug therapy alone. Methods: This retrospective cohort study consecutively enrolled patients diagnosed with persistent atrial fibrillation and moderate or severe FMR who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2021. Forty-eight patients who were treated with radiofrequency ablation and maintained sinus rhythm were enrolled in the ablation group, and 63 patients who were treated with medication alone during the same period were in the medicine group. Patients in the ablation group and medicine group were matched in a 1∶1 ratio using a propensity score, and 41 patients were finally included in each of the 2 groups. All patients reexamined echocardiography after 3-month of treatment. The proportion of patients with FMR improvement and the differences in changes of cardiac structural and functional parameters were compared between groups. Results: After propensity score matching, the ablation group was aged (69.3±7.1) years with 21 males (51.2%) and the medicine group was aged (71.3±9.4) years with 21 males (51.2%). The echocardiography after 3-month of treatment showed the rate of FMR improvement was significantly higher in the ablation group than in the medicine group (19 (46.3%) vs. 33 (80.5%), P<0.001), and patients in the ablation group showed a significant decrease in FMR extent (Δmitral regurgitation area: (-1.30±2.64) cm2 vs. (-3.55±2.50) cm2, P<0.001), left atrial size (Δleft atrial diameter: (-0.17±3.78) mm vs. (-2.46±4.01) mm, P=0.009) and E/e' (ΔE/e':-2.54±7.34 vs.-6.34±7.08, P=0.021) compared with the medicine group. There was also a significant decrease in left ventricular size (Δleft ventricular end diastolic diameter: (-3.12±6.62) mm vs. (-0.73±3.62) mm, P=0.046) and significant increase in left ventricular ejection fraction (Δleft ventricular ejection fraction: (2.73±9.69) % vs. (-0.93±5.41) %, P=0.038) in ablation group. Conclusion: Performing radiofrequency ablation to restore sinus rhythm can effectively reduce the severity of mitral regurgitation and improve left atrial and left ventricular remodeling and cardiac function in patients with atrial fibrillation and FMR.

The application of mass defect percentage in the evaluation of acute coronary syndrome.

White blood cells, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR) distribution patterns in patients with anatomic coronary disease have previously been associated with cardiac events such as myocardial infarct size, complications, and prognosis. However, it remains unknown whether myocardial perfusion mass defect percentage (MDP) obtained from gated myocardial perfusion imaging (G-MPI) correlates with these hematological parameters. Therefore, our research aimed to investigate the application of MDP in the evaluation of acute coronary syndrome (ACS). Thirty-six patients with ACS underwent single-photon emission computed tomography/computed tomography using retrospective electrocardiography gating during the resting state. The primary outcome was the percentage of left ventricular mass with abnormal myocardial perfusion (i.e. MDP) in G-MPI. Furthermore, the correlation between myocardial perfusion MDP and lymphocyte count, neutrophil count, white blood cell count, and NLR was calculated. In addition, we explored the relationship of myocardial perfusion MDP with other cardiac function parameters obtained from G-MPI, such as summed rest score, left ventricular ejection fraction, end-systolic volume, and end-diastolic volume. Myocardial perfusion MDP significantly correlated with white blood cell count, neutrophil count, and NLR (P < 0.01). Furthermore, these hematological parameters were significantly different between low and high MDP groups. Additionally, myocardial perfusion MDP negatively correlated with end-systolic volume (r = -0.615) and left ventricular ejection fraction (r = -0.657). Myocardial perfusion MDP has a high correlation with inflammatory cell counts and cardiac function parameters obtained from G-MPI in ACS; this may be of help in the evaluation and treatment of these patients.

The value of blood flow velocity and pressure gradient in differentiating patients with different types of heart failure.

Patients with different types of heart failure (HF) exhibit varying rates of blood flow through cardiac chambers and pressure gradients across the aortic valve, attributed to differing degrees of myocardial contractility. Assessment of these dynamics offers insights into early HF diagnosis. This study aimed to analyze left ventricular outflow tract (LVOT) blood flow parameters, specifically peak blood flow velocity and pressure gradient derived from four-dimensional flow cardiovascular magnetic resonance (4D flow CMR), and to evaluate 4D flow CMR's utility in distinguishing HF types. This prospective cross-sectional study recruited 115 HF patients from January 2019 to May 2022 at the General Hospital of Ningxia Medical University, classified by the New York Heart Association Cardiac Function Classification of Heart Failure as class II-IV, alongside a control group (n=30). Participants underwent cardiovascular magnetic resonance (CMR), including 4D flow. HF patients were categorized into heart failure with reduced ejection fraction (HFrEF, n=55), heart failure with mildly reduced ejection fraction (HFmrEF, n=30), and heart failure with preserved ejection fraction (HFpEF, n=30), based on ejection fraction. The cardiac functional parameters and aortic valve flow indices were measured using Circle Cardiovascular Imaging. LVOT 4D flow data were obtained 3 mm below the junction of the aortic valve leaflets, assessing peak velocities above and below the valve. Differences in cardiac function and blood flow parameters between groups were analyzed using one-way analysis of variance (ANOVA). The accuracy of these parameters in identifying subgroups was assessed using the receiver operating characteristic (ROC) curve. Analysis of conventional cardiac function parameters revealed that left ventricular ejection fraction (LVEF) was significantly lower in the HFrEF and HFmrEF groups compared to the HFpEF and control groups (P<0.01). Additionally, end-diastolic volume and end-systolic volume were significantly higher in the HFrEF and HFmrEF groups than in the HFpEF and control groups (P<0.01). However, there were no significant differences in cardiac function parameters between the HFpEF and control groups (P>0.05). Significant differences were observed in aortic valve peak pressure gradients (Supra-APGmax) among the four study groups (5.01±1.09 vs. 6.23±2.94 vs. 7.63±1.81 vs. 8.89±2.97 mmHg, P<0.05). Aortic valve peak velocities in the HFrEF group differed significantly from the HFpEF and control groups (111.31±12.05 cm/s vs. 137.2±16 vs. 147.15±24.55 cm/s, P<0.001). The ROC curve for the pressure gradient below the aortic valve had an area under the curve (AUC) of 0.728 [95% confidence interval (CI): 0.591-0.864, P=0.002], with an optimal threshold of 4.72 mmHg (sensitivity: 0.8, specificity: 0.7, Youden index: 0.5). HF patients exhibit reduced pressure gradients across the aortic valve during systole, indicative of altered intracardiac blood flow dynamics. Combining aortic valve velocities and pressure gradients can aid in distinguishing different types of HF, including HFpEF patients.

Using Doppler ultrasound to assess fetal cardiac function and pregnancy outcomes in obstetric antiphospholipid syndrome pregnancies: a case-control study.

This study aimed to evaluate fetal left ventricular function (LVF) in pregnant women with obstetric antiphospholipid syndrome (OAPS) by Doppler ultrasound and developed a clinical nomogram to predict adverse perinatal outcomes. In this prospective observational study, 105 pregnant women were enrolled and divided into the OAPS cohort (n = 60) and the control cohort (n = 45). Fetal cardiac function parameters were collected and compared between two cohorts. Univariate and multivariate analysis was conducted to select the risk factors associated with adverse perinatal outcomes, and a clinical nomogram was developed based on these selected risk factors. The predictive performance of corresponding indicators for adverse perinatal outcomes was evaluated using receiver operating characteristic (ROC) curve analysis. The OAPS cohort revealed an increase in the isovolumic relaxation time (IVRT) and myocardial performance index (MPI), a decrease in the ejection time (ET), middle cerebral artery pulsatility index (MCA-PI) and cerebroplacental ratio (CPR) compared to the control cohort. Through univariate and multivariate analysis, gravidity, CPR, and MPI were the risk factors associated with adverse perinatal outcomes. A model predicting adverse perinatal outcomes in OAPS pregnant women was constructed based on these three factors and visualized as a nomogram. The nomogram could accurately predict adverse perinatal outcomes with an area under the curve of 0.923 (95% CI: 0.858-0.982). This performance was better than evaluating individual factors such as MPI (0.825, 95% CI: 0.739-0.911) and CPR (0.816, 95% CI: 0.705-0.927) for efficacy. MPI can be used to assess fetal LVF and predict adverse perinatal outcomes. We developed a nomogram to predict adverse perinatal outcomes in OAPS women. This imaging-based evidence can provide timely clinical intervention, enabling personalized clinical decision-making.

Diffuse Interstitial Fibrosis of the Myocardium Predicts Outcome in Moderate and Asymptomatic SevereAortic Stenosis.

Patients with moderate or asymptomatic severe aortic stenosis (AS) are at risk of cardiovascular events. The authors investigated the utility of cardiac magnetic resonance (CMR) to identify drivers of outcome in patients with moderate or asymptomatic severe AS. A prospective, international, multicenter cohort (n=457) of patients with moderate (aortic valve area [AVA]: 1.0-1.5cm2) or asymptomatic severe AS (AVA≤1.0cm2 and NYHA functional class I-II) patients underwent CMR. Diffuse interstitial fibrosis and scar in the myocardium were analyzed with extracellular volume fraction (ECV%) and late gadolinium enhancement (LGE). The outcome was a composite of mortality and heart failure admission. Median ECV% was 26.6% (IQR: 24.4%-29.9%), and LGE was present in 31.5% (median 0.8%; IQR: 0.1%-1.7%). Greater AS severity was associated with greater left ventricular mass and diastolic dysfunction, but not with ECV% or LGE. During a median 5.7 years of follow-up, 83 events occurred. Patients with events had higher ECV% (median ECV% 26.3% vs 28.2%; P = 0.003). Patients in the highest ECV% tertiles (ECV% >28.6%) had worse outcomes both in the entire cohort and in those with NYHA functional class I moderate or severe AS, and ECV% was independently associated with outcome (adjusted HR: 1.05; P = 0.039). The ECV% had significant incremental prognostic value when added to parameters of AS severity and cardiac function, comorbidities, aortic valve replacement, and LGE (P< 0.05). Increased diffuse interstitial fibrosis of the myocardium is associated with poor outcomes in patients with moderate and asymptomatic severe AS and can help identify those who require closer surveillance for adverse outcomes.

Elevated carbohydrate antigen 125 (CA125) is associated with incident heart failure and mortality in acute coronary syndrome.

Carbohydrate antigen 125 (CA125), a mucin produced by serosal cells in response to mechanical and inflammatory stimuli, has emerged as an important biomarker to guide risk stratification in heart failure (HF). The prognostic value of CA125 in acute coronary syndrome (ACS) patients is less explored. In a cohort of 524 ACS patients (73% males, mean age 67±12years), we assessed the associations between CA125 and the risk for HF and death during a median follow-up period of 27.3months for incident HF and 39.5months for mortality. Plasma CA125 was measured within 24h after admission in the entire cohort and after 6weeks in a subgroup of 115 elderly patients (>75years of age). We also assessed the relationships between baseline CA125 and echocardiographic parameters of cardiac structure and function at 1year post-ACS in this subgroup. Baseline CA125 was associated with incident HF in the entire cohort in a Cox proportional hazards model adjusted for age, sex, cardiovascular (CV) risk factors (diabetes, smoking, hypertension, previous HF, previous ACS and previous stroke), renal function and revascularization {hazard ratio [HR] 1.46 [95% confidence interval (CI) 1.10-1.93] per 1-standard deviation [SD] CA125 increase; P=0.009}. In the detailed follow-up subgroup, elevated baseline CA125 predicted subsequent deterioration of left ventricular (LV) ejection fraction (LVEF), defined as a >5% absolute LVEF decrease in patients with LVEF≥50% at discharge [odds ratio (OR) 3.31 (95% CI 1.15-9.54) per 1-SD baseline CA125 increase; P=0.027]. We also found significant correlations between high baseline CA125 and larger LV volumes (LV end-diastolic volume index, Spearman's r=0.329, P<0.001; LV end-systolic volume index, r=0.391, P<0.001) and left atrial volume index (r=0.320, P<0.001) at 1year post-ACS, indicative of adverse cardiac remodelling. Elevated baseline and follow-up CA125 were associated with increased mortality, independently of age and sex [HR 1.37 (95% CI 1.09-1.71), P=0.006, per 1-SD baseline CA125; HR 1.98 (95% CI 1.06-3.67), P=0.031, per increasing 6week CA125 tertile]. The relationship between 6week CA125 and incident mortality remained significant in the fully adjusted model [HR 2.23 (95% CI 1.15-4.35) per increasing CA125 tertile; P=0.018]. We report independent associations between elevated CA125, LV dysfunction, cardiac remodelling, incident HF and mortality post-ACS. Our results warrant further evaluation of CA125 as a potential biomarker for risk stratification and management of ACS patients, both at the time of the acute coronary event and during follow-up.