Galectin-3 in single ventricle physiology: insights into fibrosis and functional impairment after Fontan procedure.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The funds of the Ministry of Education and Science. Background Cardiac imaging in patients with FSV (functionally single ventricle) underwent the Fontan procedure is a challenge. One of the most difficult issue to be resolved in FSV patients is myocardial contractility. Thus, we sought for deformation parameters analysis by STE (Speckle Tracing Echocardiography), for haemodynamic and structural reason. We incorporated a novel STE (Speckle Tracing Echocardiography) parameter– TG (transmural strain gradient) representing the difference in strain between subendocardial and subepicardial layer to assess FSV contractile reserve. The role of TG in assessment of FSV after Fontan palliation has not been evaluated yet. Purpose The study aimed to introduce/evaluate transmural longitudinal strain gradient (TG) at rest and during exercise as marker of FSV contractility and exercise performace. Methods The group of 37 patients with FSV after Fontan palliation were enrolled in our study at least 12 months after Fontan operation and in sinus rhythm on ECG. We performed an transthoracic echocardiography at rest and during exercise on a semi-supine cycle ergometer. The apical-chamber views were registered for subsequent post-processing analysis. Due to heterogeneous FSV morphology and primary defects as well as accompanying intraventricular septum segments malformation in majority of cases, we decided to measure and analyse FSV free wall longitudinal strain only. The values of layer-specific: subendocardial and subepicardial longitudinal free wall systolic strain were assessed and the gradient between them was calculated. The TG at rest and during exercise were compared with the cardiopulmonary exercise test results, NYHA class, FSV systolic function studied by CMR (Cardiac Magnetic Resonance) and NT-proBNP concentration. Results The values of TG at rest and during exercise correlated with peak oxygen uptake during the cardio-pulmonary exercise test (p = ,012 for TG at rest, p = ,031). TG during exercise was negatively correlated with CMR-derived ejection fraction (p = ,031) . There was no relationship between TG and NYHA-class and NT-proBNP. Conclusion(s) TG is a promising parameter for FSV contractility assessment. Our preliminary study suggests that it can complete traditional imaging technics and derived parameters. TG is highly associated to exercise capacity. However, utility of TG requires further investigation.

Aims/IntroductionGalectin‐3 (Gal3) contributes to insulin resistance, inflammation and obesity, the three risk factors for mild cognitive impairment (MCI) in type 2 diabetes mellitus patients.Materials and methodsA total of 134 hospitalized type 2 diabetes mellitus patients were assessed by the Montreal Cognitive Assessment method, and divided into 65 MCI and 69 controls. Levels of variables, Gal3 and Aβ42, were investigated in relation with cognitive function in both type 2 diabetes mellitus patients with MCI and high‐fat diet/streptozotocin induced type 2 diabetes mellitus rats.ResultsSignificantly higher levels of serum Gal3 and lower levels of plasma Aβ42 (all P < 0.05) were found in the MCI type 2 diabetes mellitus group as compared with the non‐MCI type 2 diabetes mellitus control. Partial correlation analysis showed that Gal3 is negatively correlated with both MMSE score (r = −0.51, P < 0.01) and Montreal Cognitive Assessment score (r = −0.47, P < 0.001) after adjustment for glycated hemoglobin, homoeostasis model assessment of insulin resistance and Aβ42 in all type 2 diabetes mellitus patients, with a stronger effect seen in the MCI type 2 diabetes mellitus group after further analysis with MCI strata. A simple logistic regression model showed that Gal3 and Aβ42 are significantly associated with MCI type 2 diabetes mellitus patients after adjustment with the covariates sex, age, body mass index, glycated hemoglobin, homoeostasis model assessment of insulin resistance and antidiabetic drugs. Serum and brain Gal3 levels were significantly increased in high‐fat diet/streptozotocin diabetic rats, which correlate to the impairment of learning and memory ability. Gal3 inhibitor modified citrus pectin decreased serum and brain Gal3 levels in diabetic rats, accompanied by the amelioration of learning and memory impairment.ConclusionsGal3 might be associated with cognitive impairment in type 2 diabetes mellitus, and serum Gal3 level might be a new risk factor of MCI in type 2 diabetes mellitus patients.

Many hypothesis suggest that inflammation plays an important role in schizophrenia. Galectins can regulate inflammatory response in central nervous system. The relation between galectins and neuropsyhchiatric diseases and schizophrenia is unclear. The present study compared levels of Gal-1 and Gal-3 of patients with schizophrenia to that of first-degree relatives without the disease and healthy controls in order to evaluate any possible association. Sixty-two patients with schizophrenia, fifty-five unaffected siblings and fifty-eight age- and sex-matched healthy controls enrolled. Serum Gal-1, Gal-3 and CRP levels were measured. PANNS and CGI-S were used to evaluate the severity of disease. There was a statistically significant difference in serum Gal-1 levels among the patient, sibling, and control groups. There were no statistically significant correlations between serum CRP ​​and serum Gal-1 or Gal-3 levels. Gal-1 values were significantly higher in the unaffected siblings compared to both the patient group and the healthy control group. Gal-3 levels were elevated in the sibling group relative to the patient group. In the literature, the relationship between galectins and schizophrenia is very limited and appears to be a new field of study. Future studies are needed to evaluate the protective roles of galectins.

The utility of novel STE parameters in echocardiographic assessment of single ventricle after Fontan palliation

Regional heterogeneity of the human heart plays an important role in left ventricular (LV) and right ventricular (RV) function and may contribute to enhanced myocardial efficiency in the athlete's heart. This study comprehensively characterized regional and transmural myocardial tissue deformation (strain) in recreationally active (RA) and endurance-trained (ET) men to determine if regional nonuniformity evolves alongside morphological adaptations associated with endurance training. Echocardiography was used to measure LV and RV global, regional (apical, mid, basal) and transmural (endocardial, epicardial) longitudinal strain in 30 endurance-trained (ET) (age, 31 ± 2 yr; body mass index, 23.1 ± 0.5 kg·m; V˙O2peak, 60.2 ± 6.5 mL·kg·min) and 30 RA (age: 29 ± 2 yr; body mass index, 23.4 ± 0.4 kg·m; V˙O2peak: 42.6 ± 4.6 mL·kg·min). Nonuniformity was characterized using apex-to-base and transmural (endocardial-to-epicardial) strain gradients. Global longitudinal strain was similar in ET and RA in the left (-17.4% ± 0.4% vs -17.8% ± 0.5%, P = 0.662) and right ventricle (-25.8% ± 0.8% vs 26.4% ± 1.0%, P = 0.717). The apex-to-base strain gradient was greater in ET than RA in the left (-6.5% ± 0.7% vs -2.7% ± 0.8%, P = 0.001) and right ventricle (-9.6% ± 1.8% vs -3.0% ± 1.6%, P = 0.010). The LV transmural strain gradient was greater than RV in both groups, but similar in ET and RA (-4.7% ± 0.2% vs -4.7% ± 0.2%, P = 0.850), whereas RV transmural strain gradient was greater in ET than RA (-3.4% ± 0.3% vs -1.6% ± 0.4%, P = 0.003). RV apex-to-base and transmural strain gradients correlated with RV end-diastolic area (R = 0.536 & 0.555, respectively, P < 0.01) and V˙O2peak (R = 0.415 & 0.677, respectively, P < 0.01). Transmural nonuniformity is more pronounced in the left ventricle than the RV free wall; however, RV functional nonuniformity develops markedly after endurance training. Differences in myocardial architecture and exercise-induced wall stress in the left and right ventricles are possible explanations for the marked functional nonuniformity throughout the myocardium and in response to endurance exercise training.

Cardiopulmonary exercise test (CPET) parameters are established prognosticators in heart failure. However, the prognostic value of preimplantation and postimplantation CPET parameters in left ventricular assist device (LVAD) therapy is unclear and it is evaluated in this study. Adult patients who were implanted with an LVAD and underwent CPET during the preimplantation or postimplantation period were retrospectively analyzed. Five CPET parameters were calculated: vO2 max, oxygen uptake efficiency slope (OUES), VE/vCO2 Slope, VE/vCO2 min, and VE/vCO2 max. The relationship between CPET parameters and postimplantation outcomes was evaluated with multivariable analysis. Pre and postimplantation CPET cohorts included 191 and 122 patients, respectively. Among preimplantation CPET parameters: vO2 max and OUES were associated with 1, 3, and 5 year mortality, VE/vCO2 min was associated with 3 and 5 year mortality, whereas VE/vCO2 Slope was associated with 5 year mortality. From postimplantation CPET parameters: vO2 max was an independent predictor of 3 and 5 year mortality, whereas VE/vCO2 max was an independent predictor of 3 year mortality following LVAD implantation. Preimplantation CPET parameters have a prognostic value for long-term survival following LVAD implantation, whereas their association with early postimplantation outcomes appears to be weaker. Postimplantation vO2 max and VE/vCO2 max values are associated with survival on device support and may provide a second chance for prognostication in patients without preimplantation CPET data.

Fontan-associated liver disease.

Management of the bad atrioventricular valve in Fontan…time for a change

Background: Optimum timing of surgery for severe primary mitral regurgitation (MR) particularly in the absence of significant symptoms or echo evidence of LV impairment remains unclear. Other modalities of assessment include cardiopulmonary exercise testing (CPET) and novel echo measurements, such as LV global longitudinal strain (LVGLS). We sought to evaluate whether pre-op CPET or LVGLS are associated with survival after surgery. Methods: We identified consecutive patients who had surgery for severe primary MR between 2007 and 2017 and had pre-op CPET. Clinical and mortality data were collected from chart review and our institutional database. LVGLS was retrospectively collected by a single person blinded to patient outcomes. Primary outcome was post surgery all cause death, and we used univariable analysis to identify variables associated with all cause death. Results: We included 176 patients with median age 63 (IQR 51, 71) years, 63 patients (35.8%) were female and 31 patients (14.8%) had a history of atrial fibrillation. 165 patients (93.8%) had mitral repair, 18 (10.2%) had concomitant CABG, 22 (12.5%) had concomitant ablation procedure and 14 (8.0%) had concomitant tricuspid procedure. 114 patients (64.8%) were in NYHA Class I and 56 (31.8%) were in NYHA Class II. There was no operative mortality. Median % predicted peak VO2 (ppVO2) was 89 (74, 101), median ventilatory equivalent of carbon dioxide (VE/VCO2) was 28.0 (25.7, 31.0) l/min/l/min and median respiratory exchange ratio was 1.2 (1.1, 1.2). 73 patients (41.5%) had abnormal CPET (defined as ppVO2&lt;85%). Median LVEF was 65 (60, 68) %, median LVESD was 35 (32, 38) mm and median LVGLS was 18.5 (16.6, 20.3) %. 45 patients (25.9%) had abnormal LVEF (defined as ≤ 60%), 11 patients (6.7%) had abnormal LVESD (defined as ≥45mm) and 35 patients (20.8%) had abnormal LVGLS (defined as &lt;16%). At a median follow up of 10.2 (6.8, 13.2) years, there were 19 (10.8%) deaths. In the univariate analysis, age at surgery (HR 1.12, p&lt;0.001), LVESD (HR 1.11, p=0.009), LVGLS (HR 1.11, p=0.013) and VE/VCO2 (HR 1.08, p=0.044) were associated with all cause mortality. Conclusion: A significant proportion of patients with no or mild symptoms exhibit echocardiographic evidence of LV impairment when having surgery for severe primary MR. CPET parameters such as VE/VCO2 and novel echocardiographic measurements such as LVGLS may predict risk of long term mortality and potentially inform timing of surgery in these patients.

To evaluate the diagnostic and prognostic value of insulin-like growth factor-1 (IGF-1), galactoagglutinin-3 (GAL-3), and pentamerin-3 (PTX-3) levels in elderly patients with chronic heart failure (CHF). In this retrospective study, 107 elderly CHF patients treated in Xiangyang Central Hospital were designated as the observation group, and 60 healthy individuals were selected as the control group. The cardiac function indexes and serum IGF-1, Gal-3, and PTX-3 levels were compared between the two groups. Furthermore, the serum IGF-1, Gal-3, and PTX-3 levels in patients across different cardiac function grades were compared, as well as in patients with poor or favorable prognosis. Additionally, receiver operating characteristic (ROC) curve was adopted to explore the diagnostic value of serum IGF-1, Gal-3, and PTX-3 levels for senile CHF; and multivariate logistic regression analysis was used to screen the independent factors affecting patients' prognosis. The serum IGF-1 level was significantly lower, while the levels of Gal-3 and PTX-3 were significantly higher in the observation group than those of the control group (all P<0.05). The serum IGF-1 level in patients with cardiac function grade IV was lower than that of the patients with cardiac function grade II and III, while the levels of Gal-3 and PTX-3 were higher than those with cardiac function grade II and III (all P<0.05). The serum IGF-1 level in the patients with cardiac function grade III was lower than those with cardiac function grade II, while the levels of Gal-3 and PTX-3 were higher in patients with grade III than those with grade II (all P<0.05). The serum IGF-1 level was lower, while the levels of Gal-3 and PTX-3 were higher in the patients with poor prognosis than those with favorable prognosis (all P<0.05). In elderly CHF patients, IGF-1 level were decreases, while the levels of Gal-3 and PTX-3 were increase. These biomarkers show high sensitivity in diagnosing CHF and are closely linked to the prognosis, indicating their value for clinical assessment and management of CHF.

Aim: To perform comprehensive evaluation of the Cardiopulmonary Exercise Testing (CPET) parameters with gas analysis in patients with pulmonary sarcoidosis (PS) and to assess the effects of hemodynamic limitations on the reduction of exercise capacity (EC).Materials and methods: We examined 42 PS patients (25 men, 17 women) aged from 22 to 62 years (34.5 [29; 41.5] years old). PS had been verified histologically in 33 (78.6%) patients. The group 1 included patients with decreased oxygen consumption per minute at the peak load (n = 20) with VO₂ peak pred ≤ 84%, i.e. with decreased EC. Group 2 consisted of 22 patients with normal VO₂ peak pred (&gt; 84%). In all patients, echocardiographic and CPET parameters were assessed that characterize response of the cardiovascular system to physical exercise, such as oxygen consumption at the anaerobic threshold (VO₂ AT, % of predicted value); oxygen pulse (VO₂/HR, abs/% of predicted), the chronotropic-metabolic index (CMI), and blood pressure.Results: Thickening of the left ventricular posterior wall (p = 0.012) was found in the group 1, together with decreased VO₂ AT (р &lt; 0.001), VО₂/HR (р &lt; 0.001), and systolic blood pressure (p = 0.037) at the peak load during CPET, compared to the parameters in the group 2. Twelve patients from the group 1 demonstrated their VO₂ AT &lt; 43%, 6 patients had decreased VО₂/HR &lt; 80% of predicted, and 3 patients were diagnosed with the chronotropic incompetence phenomenon.Conclusion: Decreased EC was identified by CPET in 47.6% of PS patients without any functional abnormalities at rest. The reduction of EC in 17/20 PS patients from the group 1 was associated with abnormalities in CPET parameters, corresponding to the hemodynamic limitations (reduction of cardiac output and chronotropic incompetence).

Mechanical support for the failing single ventricle after Fontan

This study aims to assess left ventricular (LV) function and exercise endurance in patients with hypertrophic cardiomyopathy (HCM) using a combination of left ventricular pressure-strain loop (LV-PSL) and cardiopulmonary exercise testing (CPET), and to explore the correlation of the maximum left ventricular wall thickness (MWT) with clinical, echocardiographic, and CPET parameters. A total of 55 patients with non-obstructive HCM, diagnosed between January 2022 and March 2023 at Longyan First Affiliated Hospital of Fujian Medical University, were included, along with 55 healthy volunteers as a control group. Two-dimensional ultrasound speckle tracking technology was used to obtain global longitudinal strain (GLS), longitudinal strain peak time dispersion (PSD), as well as the myocardial global work index (GWI), myocardial global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). The differences in these parameters were compared between the two groups before and after CPET. CPET was used to measure peak oxygen consumption (Peak VO2), anaerobic threshold (AT), ventilation equivalent for carbon dioxide slope (VE/VCO2 slope), oxygen pulse (VO2/HR), and metabolic equivalents (METs), and the differences between the two groups were also compared. Compared to the control group, the HCM group showed significant reductions in GLS, GWI, GCW, and GWE, while GWW and PSD were significantly increased, with statistical significance (P < 0.05). Peak VO2, AT, VO2/HR, and METs were significantly lower in the HCM group compared to the control group, while VE/VCO2 slope did not show a significant increase (P > 0.05). After CPET, GWI and GCW did not increase significantly in the HCM group (P > 0.05), whereas GWW and PSD showed significant increases (P < 0.05). In contrast, in the control group, GWI and GCW increased significantly after CPET (P < 0.05), and no significant changes were observed in GWW and PSD (P > 0.05). Univariable linear regression analysis showed that MWT was correlated with NYHA classification, GLS, PSD, GCW, GWW, Peak VO2, and AT (P < 0.05). Multivariate linear regression analysis confirmed the independent associations of MWT with PSD, GCW, and GWW (P < 0.05). LV-PSL combined with CPET is effective in early detection of left ventricular function and exercise endurance impairment in HCM patients, providing valuable information for clinical decision-making.

The precise head to head relationships between Cardio-pulmonary exercise testing (CPET) parameters and patients' daily symptoms/activities and the disease social/emotional impact are less well defined. In this study, the correlation of COPD daily symptoms and quality of life [assessed by St. George's Respiratory Questionnaire (SGRQ)] and COPD severity index (BODE-index) with CPET parameters were investigated. Symptom-limited CPET was performed in 37 consecutive COPD (GOLD I-III) subjects during non-exacerbation phase. The SGRQ was also completed by each patient. SGRQ-score correlated negatively with FEV1 (r=-0.49, P<0.01), predicted maximal work-rate (%WR-max) (r=-0.44, P<0.01), V'O2/WR (r=-0.52, P<0.01) and breathing reserve (r=-0.50, P<0.01). However it did not correlate with Peak-V'O2% predicted (r=-0.27, P=0.10). In 20 (54.1%) subjects in which leg fatigue was the main cause for stopping the test, Peak-V'O2, %WR-max, HR-Reserve and Breathing reserve were higher (P=0.04, <0.01, 0.04 and <0.01 respectively) than the others. There was also a significant correlation between BODE-index and ∆VO2/∆WR (r=-0.64, P<0.001) and breathing-reserve (r=-0.38, P=0.018). The observed relationships between CPET parameter and daily subjective complaints in COPD were not strong. Those who discontinued the CPET because of leg fatigue were in the earlier stages of COPD. Significant negative correlation between ∆VO2/∆WR and BODE-index suggests that along with COPD progression, regardless of negative past history, other comorbidities such as cardiac/musculoskeletal problems should be sought.

Simple SummaryGalectin-3 (gal-3) regulates many different biological processes and diseases, which are common accompanying diseases of psoriasis. Psoriasis is one of the most common skin diseases. There is little information about potential diagnostic role of gal-3 in psoriasis. Serum gal-3 concentrations were measured before and after twelve weeks of antipsoriatic treatment in patients with psoriasis and compared to 11 persons without psoriasis (control group). Serum gal-3 level in patients with psoriasis was significantly higher compared to the control group. In obese patients and long-lasting psoriasis positive relations of gal-3 and index of psoriasis severity were noted. In psoriatics with low gal-3 levels, it was noted that the higher the gal-3, the higher the BMI and glucose level. In patients with long history of psoriasis it was observed that the higher gal-3, the lower the lipids levels. The Gal-3 level might be a factor affecting the course of psoriasis and useful in prediction of cardiometabolic comorbidities, especially in patients with a long history of the disease or obesity. Patients with low serum gal-3 and a short history of psoriasis may have greater risk of diabetes. In obese patients with long-lasting psoriasis, gal-3 may have a beneficial influence against abnormal lipid profiles or perhaps further cardiovascular disorder development.Galectin-3 (gal-3) is a multifunctional regulator of various biological processes and diseases, which are common comorbidities in psoriasis. Data regarding potential diagnostic role of gal-3 in psoriasis are insufficient. Serum gal-3 levels were evaluated before and after twelve weeks of treatment with acitretin or methotrexate in 31 patients with plaque-type psoriasis and compared to 11 healthy control group. The mean serum galectin-3 level in patients with psoriasis was significantly higher compared to the control group (p < 0.01). In patients with obesity and long-lasting psoriasis (>20 years) positive relations of gal-3 and PASI were noted. In psoriatics with low gal-3 levels, positive correlations between the gal-3 and BMI, glucose level, and with the latter in short-lasting psoriasis (<20 years) were noted. In the long history of psoriasis, gal-3 was negatively correlated with lipids levels. The Gal-3 level might be a multifaceted modulator of the course of psoriasis and predictive factor of cardiometabolic comorbidities’ development, especially in patients with a long history of the disease or obesity. Patients with low serum gal-3 and short history of psoriasis are presumably at greater risk of diabetes. In patients with long-lasting psoriasis and concomitant obesity, gal-3 may exert a protective role against dyslipidemia or perhaps further CMD development.