Dietary chlorogenic acid alleviates high-fat diet-induced steatotic liver disease by regulating metabolites and gut microbiota.

The high-fat diet would lead to excessive fat storage in the liver to form metabolic dysfunction-associated steatotic liver disease (MASLD), and the trend is burgeoning. The aim of the study is to investigate the effects of chlorogenic acid (CGA) on metabolites and gut microorganisms in MASLD mice induced by a high-fat diet. In comparison to the HF group, the TC (total cholesterol), TG (total triglycerides), LDL-C (low-density lipoprotein cholesterol), AST (aspartate aminotransferase) and ALT (alanine transaminase) levels were reduced after CGA supplement. CGA led to an increase in l-phenylalanine, l-tryptophan levels, and promoted fatty acid degradation. CGA increased the abundance of the Muribaculaceae, Bacteroides and Parabacteroides. Changes in these microbes were significantly associated with the liver metabolites level and lipid profile level. These data suggest important roles for CGA regulating the gut microbiota, liver and caecum content metabolites, and TG-, TC- and LDL-C lowering function.

Effects of ketamine-induced H3K9 hypoacetylation during pregnancy on cardiogenesis of mouse offspring.

BACKGROUND: Prenatal exposure to adverse factors can cause congenital heart defects. Ketamine, a widely used anesthetic drug, produces several adverse reactions such as tachycardia, hypertension, and laryngospasm, especially in pediatric patients. This study aimed to detect the effects of ketamine exposure during pregnancy on the cardiogenesis of mouse offspring and the potential mechanisms. METHODS: In this study, ketamine at an addictive dose (5 mg/kg) was administered to mice during early gestation to explore the epigenetic mechanism of its causing cardiac dysplasia. The cardiac morphology of the mouse offspring was observed through hematoxylin-eosin staining and transmission electron microscopy. The heart function of one-month-old neonates was detected by echocardiography. The expression of cardiomyogenesis-related genes was detected by western blot and RT-qPCR. The acetylation level of histone H3K9 at the Mlc2 promoter and its deacetylase level and activity were detected by CHIP-qPCR, RT-qPCR, and ELISA, respectively. RESULTS: Our data revealed that ketamine exposure during pregnancy could cause cardiac enlargement, myocardial sarcomere disorganization, and decreased cardiac contractile function in mouse offspring. Moreover, ketamine reduced the expression of Myh6, Myh7, Mlc2, Mef2c, and cTnI. The histone H3K9 acetylation level at the Mlc2 promoter was down-regulated by increasing the histone deacetylase activity and HDAC3 level upon ketamine administration. CONCLUSIONS: Our work indicates that H3K9 acetylation is a vital player in cardiac dysplasia in offspring caused by prenatal ketamine exposure and HDAC3 is a key regulatory factor.

Citrus peel ameliorates mucus barrier damage in HFD-fed mice.

Citrus peel is rich in bioactive components, especially polyphenols, which are considered to have great potential in the prevention of intestinal diseases. The intestinal mucus barrier is the first defense against the invasion of foreign substances. In this study, we aimed to explore the possibility and mechanism of citrus peel in alleviating the mucus barrier damage in high-fat-diet (HFD) mice. We found that citrus peel powder (CPP) supplementation effectively reduced body weight, fat weight, intestinal permeability, hyperlipidemia, and systemic inflammation in HFD-fed mice. In particular, CPP increased the number of goblet cells, the protein expression of Mucin-2 (Muc2), and the thickness of the mucus layer, thereby strengthening the colonic mucus barrier function. Moreover, CPP supplementation also reduced the expression of endoplasmic reticulum stress (ERS) proteins (GRP78 and CHOP) and increased the expression of T-synthase (O-glycosylation rate-limiting enzyme) and its chaperone protein (Cosmc) in the colon of HFD-fed mice, which suggested that CPP could improve the abnormal protein folding and O-glycosylation of Muc2 during processing and modification. In summary, our study indicates that CPP plays an effective role in relieving mucus barrier damage by improving the production and properties of Muc2, providing new perspectives on the development of CPP as a dietary supplement for strengthening the intestinal barrier.

Pollution Risk Assessment and Sources Analysis of Heavy Metal in Soil from Bamboo Shoots.

In order to investigate the pollution situation and sources analysis of heavy metals in bamboo shoot soil in Guangdong Province, a total of 175 soil samples were collected at 46 sites. Atomic fluorescence spectrophotometer and inductively coupled plasma mass spectrometry were used to determine the content of five heavy metals: lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and chromium (Cr). In addition, the soil environmental quality was evaluated through different index methods, including single-factor pollution, Nemeiro comprehensive pollution, geoaccumulation, and potential ecological risk. Furthermore, the correlation coefficients were also discussed. The results showed that the soils collected were acidic or slight alkaline. The maximum content of Pb and As from some areas exceeded the standard limit value. The coefficient of variation value from six areas exceeded 100%. The index method mentioned above confirmed that the soil within study areas was divided into three pollution levels: no, slightly, and mild. Additionally, there was a very significant correlation between pH and Pb, Hg; the correlation between heavy metal As and Pb, Cr also reached a very significant level. The principal component analysis results show that PC1 accounts for 39.60% of the total variance, which includes Pb, Cd, and As. PC2 mainly includes Hg and Cr.

A novel conductive carbon-based forward osmosis membrane for dye wastewater treatment.

Forward osmosis (FO) membrane fouling is one of the main reasons that hinder the further application of FO technology in the treatment of dye wastewater. To alleviate membrane fouling, a conductive coal carbon-based substrate and polydopamine nanoparticles (PDA NPs) interlayer composite FO membrane (CPFO) was prepared by interfacial polymerization (IP). CPFO-10 membrane prepared by depositing 10 mL of PDA NPs solution exhibited an optimum performance with water flux of 7.56 L/(m2h) for FO mode and 10.75 L/(m2h) for pressure retarded osmosis (PRO) mode, respectively. For rhodamine B and chrome black T dye wastewater treatment, the water flux losses were reduced by 21.6%, and 14.5% under the voltages of +1.5 V, and -1.5 V, respectively, compared with no voltage applied after the device was operated for 8 h. The applied voltage had little effect on the fouling mitigation performance of the CPFO membrane for neutral charged cresol red. After the device was operated for 4 cycles, the rejection rates of dyes wastewater treated by the CPFO membranes with applied voltage were close to 100%. The flux decline rate and flux recovery rate of CPFO membrane for rhodamine B and chrome black T wastewater treatment under application of +1.5 V and -1.5 V voltage after 4 cycles were 11.6%, 99.2%, and 16.7%, 98.9%, respectively. Therefore, the voltage-applied CPFO membrane still maintained good rejection and antifouling performance in long-term operation. This study provides a new insight into the preparation of conductive FO membranes for dye wastewater treatment and membrane fouling control.

Si-Wu Water Extracts Protect against Colonic Mucus Barrier Damage by Regulating Muc2 Mucin Expression in Mice Fed a High-Fat Diet.

A high-fat diet (HFD) could cause gut barrier damage. The herbs in si-wu (SW) include dang gui (Angelica sinensis (Oliv.) Diels), shu di huang (the processed root of Rehmannia glutinosa Libosch.), chuan xiong (rhizome of Ligusticum chuanxiong Hort.), and bai shao (the root of Paeonia lactiflora f. pilosella (Nakai) Kitag.). Si-wu water extracts (SWE) have been used to treat blood deficiency. Components of one herb from SW have been reported to have anti-inflammatory and anti-obesity activities. However, there have been no reports about the effects of SWE on gut barrier damage. Therefore, the aim of the study was to explore the effect of SWE on gut barrier damage. In this study, we found that SWE effectively controlled body weight, liver weight, and feed efficiency, as well as decreased the serum TC level in HFD-fed mice. Moreover, SWE and rosiglitazone (Ros, positive control) increased the colonic alkaline phosphatase (ALP) level, down-regulated serum pro-inflammatory cytokine levels, and reduced intestinal permeability. In addition, SWE increased goblet cell numbers and mucus layer thickness to strengthen the mucus barrier. After supplementation with SWE and rosiglitazone, the protein expression of CHOP and GRP78 displayed a decrease, which improved the endoplasmic reticulum (ER) stress condition. Meanwhile, the increase in Cosmc and C1GALT1 improved the O-glycosylation process for correct protein folding. These results collectively demonstrated that SWE improved the mucus barrier, focusing on Muc2 mucin expression, in a prolonged high-fat diet, and provides evidence for the potential of SWE in the treatment of intestinal disease-associated mucus barrier damage.

Osteogenic Circulating Endothelial Progenitor Cells are Associated with Vascular Aging of the Large Arteries in Rheumatoid Arthritis.

Background and Aim: Rheumatoid arthritis is associated with both abnormal bone metabolism and accelerated vascular aging but a mechanistic link was lacking. This study aims to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPCs) in vascular aging, as determined by arterial calcifications in rheumatoid arthritis. Methods: We performed flow cytometry studies in 145 consecutive patients with rheumatoid arthritis to determine osteogenic circulating levels of OCN-positive (OCN+) CD34+KDR+ and OCN+CD34+ versus conventional early EPC CD34+CD133+KDR+. Total calcium load of the thoracic aorta (ascending plus descending) and the carotid arteries were assessed by non-contrast computed tomography (CT) and contrast CT angiography. Results: Osteogenic EPCs OCN+CD34+KDR+ (P = 0.002) and OCN+CD34+ (P = 0.001), together with clinical parameters of age, history of hypertension, systolic blood pressure, serum levels of triglycerides, HbA1c and creatinine, use of leflunomide and brachial-ankle pulse-wave velocity (all P < 0.05), were associated with the clustered presence of aortic and carotid calcification. Multivariable analyses revealed that circulating OCN+CD34+KDR+ (B = 14.4 [95% CI 4.0 to 24.8], P = 0.007) and OCN+CD34+ (B = 9.6 [95% CI 4.9 to 14.3], P < 0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B = 0.8 [95% CI 0.1 to 1.5], P = 0.023), but not OCN+CD34+KDR+ EPC (B = 1.2 [95% CI -0.2 to 2.6], P = 0.09), was further independently associated with carotid calcium load. In comparison, conventional early EPC CD34+CD133+KDR+ had no significant association with aortic or carotid calcium load (P = 0.46 and 0.88, respectively). Conclusion: Circulating level of osteogenic EPC is associated with increased vascular aging in terms of calcification of the large arteries in patients with rheumatoid arthritis. The findings may suggest a role of the bone-vascular axis underlying vascular aging in rheumatic diseases. Further research is needed to characterize the mechanistic links and basis of these observations.

Prevalence and Prognostic Importance of Massive Tricuspid Regurgitation in Patients Undergoing Tricuspid Annuloplasty With Concomitant Left-Sided Valve Surgery: A Study on Rheumatic Valvular Heart Disease.

BACKGROUND: The presence of tricuspid regurgitation (TR) is very common in patients with concomitant left-sided valve disease. Recent studies have advocated an additional grading of massive TR that is beyond severe. The present study sought to characterize the spectrum of TR in patients undergoing tricuspid annuloplasty (TA) and to evaluate the prognostic value of TR severity for post-operative outcome following TA. METHODS: A total of 176 patients who underwent TA with combined left-sided valve surgery, secondary to rheumatic valvular heart disease, were prospectively evaluated. The severity of TR was quantified by effective regurgitant orifice area (EROA) using the proximal isovelocity surface area method. Patients were categorized as having non-massive TR (EROA < 0.6 cm2) or massive TR (EROA ≥ 0.6 cm2). Adverse outcome was defined as all-cause mortality or heart failure requiring hospital admission following TA. RESULTS: A total of 55 (31%) patients were considered to have massive TR. Patients with massive TR had a greater right ventricular dimension but a smaller left ventricular dimension compared with those with non-massive TR. After a median follow-up of 39 months, 35 adverse events occurred. Cox-regression analysis showed that both continuous EROA and dichotomized EROA (massive vs. non-massive TR) were independently associated with adverse events even after multivariable adjustment. Further, Harrell C index demonstrated that the addition of massive TR provided better discrimination ability of a prediction model to known prognosticators following TA. CONCLUSIONS: Massive TR is common and up to 31% of study population had massive TR. Massive TR was associated with adverse outcome in patients undergoing TA. Classification of the severity of TR by quantitative measures and identification of massive TR in patients with concomitant left-sided valve disease are essential when considering the optimal timing of corrective surgery.

Prognostic value and reversibility of liver stiffness in patients undergoing tricuspid annuloplasty.

BACKGROUND: Liver stiffness (LS) assessed by transient elastography is associated with adverse events in patients with heart failure. However, the predictive value of LS for adverse outcome is uncertain in patients undergoing tricuspid annuloplasty (TA). This study sought to evaluate the prognostic value and reversibility of LS in patients undergoing TA during left-sided valve surgery. METHODS AND RESULTS: A total of 158 patients who underwent TA were prospectively evaluated. Patients were divided into three groups according to tertile of LS. Adverse outcome was defined as heart failure that required hospital admission or all-cause mortality following TA. The median LS was 13.9 (inter-quartile range 8.1-22.3) kPa and independently correlated positively with tricuspid regurgitation (TR) severity, inferior vena cava diameter and negatively with tricuspid annular plane systolic excursion. During a median follow-up of 31 months, 49 adverse events occurred. Multivariable Cox regression analysis revealed that LS was an independent predictor of adverse events. Significant improvement in LS at 1-year post-TA (13.1-7.8 kPa, P < 0.01) was noted only in patients who had no adverse events, not in those who experienced heart failure (17.1-14.2 kPa, P = 0.87) and seems to be linked to an absence of TR recurrence. CONCLUSIONS: This study demonstrated that LS is predictive of adverse outcome and is reversible in patients undergoing TA without TR recurrence at 1 year. These findings suggest that assessing LS, an integrative correlate of right heart condition, may aid the pre-operative risk assessment of candidate for heart surgery including TA.

The Regulatory Effects of Citrus Peel Powder on Liver Metabolites and Gut Flora in Mice with Non-Alcoholic Fatty Liver Disease (NAFLD).

Gannan navel orange and Jinggang pomelo, belonging to the genus Citrus, are good sources of phenolic compounds, which are mainly concentrated in the peel. These phenolic compounds are considered promising in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). In order to maximize nutrients retention and bioactivity in the peel, pomelo peel and orange peel were processed using freeze-drying technology and mixed in the ratio (pomelo peel powder 50% and orange peel powder 50%) to make citrus peel powder (CPP). The purpose of this study was to explore new strategies and mechanisms associated with the consumption of CPP to alleviate nonalcoholic fatty liver injury, lipid metabolism disorders, and gut microbiota dysbiosis in obese mice induced by high-fat diet (HFD). The results showed that after 12 weeks of CPP administration, CPP supplementation had a strong inhibitory effect on HFD-induced weight gain, hepatic fat accumulation, dyslipidemia, and the release of pro-inflammatory cytokines. In particular, CPP modulates the composition of the intestinal flora, such as increasing the relative abundance of phylum Firmicutes, genus Faecalibaculum, genus Lactobacillus, genus Dubosiella, and genus Lachnospiraceae_NK4A136_ group and decreasing the relative abundance of phylum Bacteroidota, genus Helicobacter, and genus Bacteroides. These results suggest that CPP has a preventive effect on NAFLD, which can be related to the regulation of intestinal flora.

Sex-specific pattern of left ventricular hypertrophy and diastolic function in patients with type 2 diabetes mellitus.

AIMS: Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodelling, and diastolic dysfunction in patients with type 2 diabetes (T2DM). The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodelling, and diastolic dysfunction in patients with T2DM. Further, the prognostic value of diastolic function in women and men was also evaluated. METHODS AND RESULTS: A total of 350 patients with T2DM (mean age 61 ± 11 years; women, 48.3%) was recruited. Detailed echocardiography was performed at baseline and after 25 months. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization, or myocardial infarction. Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 21 patients developed MACE (5 cardiovascular death, 9 hospitalization for heart failure, and 7 myocardial infarction) during a median follow-up of 56 months. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women [hazard ratio = 6.30; 95% confidence interval (CI) = 1.06-37.54; P < 0.05] but not men (hazard ratio = 2.29, 95% CI = 0.67-7.89; P = 0.19). CONCLUSION: LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men.

Association between adipocyte fatty acid-binding protein with left ventricular remodelling and diastolic function in type 2 diabetes: a prospective echocardiography study.

BACKGROUND: The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM. METHODS: Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively. RESULTS: The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e' (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (ß = 0.89, P < 0.01) and worsening of average E/e' (ß = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16-6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease. CONCLUSION: Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.

The prevalence, predictors, and prognosis of tricuspid regurgitation in stage B and C heart failure with preserved ejection fraction.

AIMS: Previous studies have demonstrated that moderate/severe tricuspid regurgitation (TR) is associated with adverse outcome in patients with heart failure (HF) with reduced ejection fraction. Little is known about the prevalence and prognostic value of TR in patients of stage B HF and those with stage C HF with preserved ejection fraction (HFpEF). We aimed to investigate the prevalence and prognosis of TR in patients with HFpEF. METHODS AND RESULTS: From 2013 to 2017, 2014 patients with stage B (n = 1341) or C (n = 673) HFpEF were enrolled in the study. Detailed transthoracic echocardiogram was performed, and the severity of TR was graded as no, mild, moderate, and severe. The mean age of the study population was 66.7 ± 14.1 years old, and 46% were men. Mean left ventricular ejection fraction was 62.2 ± 5.5%. The prevalence of moderate/severe TR increased from stage B to C HF (8% to 16%, respectively, P < 0.01). Older age, hyperlipidaemia, atrial fibrillation, left ventricular mass, and right ventricular systolic pressure were independently associated with moderate/severe TR (P < 0.05 for all). With a median follow-up of 3.8 (2.9-4.7) years, 346 patients died and 234 developed HF requiring hospitalization. Kaplan-Meier curve revealed that the presence of moderate/severe TR was associated with all-cause mortality, HF requiring hospitalization and cardiovascular death (log-rank test P < 0.01). Multivariable analysis demonstrated that moderate (hazard ratio = 1.5; 95% confidence interval: 1.1-2.2; P < 0.05) and severe TR (hazard ratio = 2.1; 95% confidence interval: 1.3-3.3; P < 0.01) were independently associated with mortality, HF requiring hospitalization and cardiovascular death. CONCLUSIONS: The presence of moderate/severe TR is not uncommon in patients with stage B HF and stage C HFpEF. Importantly, moderate/severe TR was independently associated with mortality and HF requiring hospitalization.

Nonapical Right Ventricular Pacing Is Associated with Less Tricuspid Valve Interference and Long-Term Progress of Tricuspid Regurgitation.

BACKGROUND: Tricuspid regurgitation (TR) is a well-known complication after permanent pacemaker implantation. The aim of this study was to compare the degree of TR and the relationship of lead position across the tricuspid valve (TV) between patients with right ventricular apical (RVA) and non-RVA pacing determined by three-dimensional echocardiography. METHODS: Conventional and three-dimensional echocardiography was performed in 284 patients to determine the change in TR severity following permanent pacemaker implantation. Transvenous lead locations were based on fluoroscopic images. This was a retrospective study, and the selected pacing mode was not randomized. RESULTS: RVA pacing had more frequent severe TR (37.9% vs 25.7%, P = .03) compared with non-RVA pacing. Severe TR occurred in 9.7%, 12.6%, and 58.8% of patients when the lead passed through the middle, between the commissures, and impinging the TV leaflets, respectively. Non-RVA leads were more likely to be positioned in the middle of the TV (30.3% vs 12.1%, P < .01) and had the lowest chance of leaflet impingement (33.6% vs 51.5%, P < .01) compared with RVA leads. RVA pacing was associated with worsening of grade ≥2 TR severity compared with non-RVA pacing (42.4% vs 27.6%, P < .01). A TV lead passage angle of -15° to 15° minimized TR. CONCLUSIONS: Pacing-induced TR is more prevalent with RVA than non-RVA pacing. Preferential lead impingement on the TV leaflet, as determined by TV lead passage angle, can explain the development and progression of pacing-induced TR.

Cardiovascular events prediction by left ventricular longitudinal strain and serum high-sensitivity troponin I in patients with axial spondyloarthritis.

OBJECTIVE: Patients with axial spondyloarthritis (SpA) are subjected to elevated cardiovascular risks, but assessment of early myocardial damage and clinical risk stratification remained obscure. The aim of this study was to evaluate the prognostic value of speckle-tracking strain analysis and serum high-sensitivity troponin I (hsTnI) in patients with axial SpA. METHODS: Two-dimensional speckle-tracking echocardiography was performed to derive longitudinal strain (LS), circumferential strain (CS), and radial strain (RS). Serum hsTnI was measured by validated immunoassay (Architect i1000SR Abbott) as indicator of subclinical myocardial damage. RESULTS: The mean Bath Ankylosing Spondylitis Disease Activity Index and median modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) were 3.8 and 15.5, respectively. Over a median follow-up of 81 months, major adverse cardiovascular events (MACE) occurred in 13% of subjects (n = 116). Univariate Cox regression showed that age, disease duration, Bath Ankylosing Spondylitis Functional Index, modified Schober test, mSASSS, hsTnI, interventricular septal thickness, E/E', LS, RS, and carotid intima-media thickness were significant predictors of MACE (all P < 0.05). After adjustment for age, sex, and statistically significant disease-related parameters, only subclinically raised hsTnI and impaired LS remained independent predictors for MACE. Kaplan-Meier analysis showed that combined impaired LS ≥ - 17.5% and hsTnI ≥ 3.0 pg/ml significantly predicted MACE (log-rank test P < 0.01; sensitivity 50%; specificity 90%; positive predictive value 43%; negative predictive value 92%). CONCLUSIONS: Depressed LS indicating subclinical left ventricular systolic dysfunction and elevated serum hsTnI both independently predicted MACE among young patients with axial SpA. Combined analysis of speckle-tracking-derived strain analysis and serum hsTnI improves risk stratification in these patients. Key Points • Both depressed longitudinal strain (LS) and elevated serum high-sensitivity troponin I (hsTnI) are promising independent predictors for cardiovascular (CV) events in axial SpA. • Importantly, patients with LS ≥ - 17.5% and hsTnI ≥ 3.0 pg/ml had the highest risk of incident MACE. • Axial SpA patients with concomitant impaired LS and raised hsTnI are at a high risk of CV events.

Prognostic Value of Tricuspid Valve Geometry and Leaflet Coaptation Status in Patients Undergoing Tricuspid Annuloplasty: A Three-Dimensional Echocardiography Study.

BACKGROUND: The advent of three-dimensional echocardiography (3DE) enables detailed evaluation of the tricuspid valve (TV) apparatus; nonetheless, the clinical value of preoperative 3DE is unknown in patients undergoing tricuspid annuloplasty (TA). The aim of this study was to evaluate the prognostic value of TV geometric parameters and leaflet coaptation status evaluated by 3DE in patients undergoing TA. METHODS: A total of 122 patients who underwent TA during left-sided heart valve surgery were prospectively evaluated. Detailed 3DE was performed before surgery. Adverse outcome was defined as the occurrence of heart failure requiring hospital admission or all-cause mortality following TA. RESULTS: A total of 33 adverse events (17 heart failures and 16 deaths) occurred during a median follow-up of 36 months. Tethering volume (hazard ratio = 1.32; 95% CI = 1.05-1.66; P = .01) and ratio of total leaflet length to closure length (hazard ratio = 1.07; 95% CI = 1.03-1.12; P < .01) were associated with adverse events after adjustment for age, sex, and tricuspid regurgitation vena contracta width. Receiver-operator characteristic curve analysis revealed that tethering volume (area under curve = 0.73) and ratio of total leaflet length to closure length (area under curve = 0.75) were most associated with adverse events at 1-year follow-up. The presence of either a large tethering volume or a low ratio of total leaflet length to closure length was predictive of an adverse outcome 1 year following TA. CONCLUSIONS: Our study suggests that 3DE-derived TV tethering volume and ratio of total leaflet length to closure length are important preoperative measures associated with adverse events in patients undergoing TA.

Cumulative Rheumatic Inflammation Modulates the Bone-Vascular Axis and Risk of Coronary Calcification.

Background Rheumatic diseases are related to both abnormal bone turnover and atherogenesis, but a mechanistic link was missing. Methods and Results We investigated the effect of cumulative rheumatic inflammation ( CRI ) on risk of coronary calcification in a retrospective cohort of 145 rheumatoid arthritis patients. A time-adjusted aggregate CRI score was derived by conglomerating all quarterly biomarker encounters of serum C-reactive protein over 60 months immediately preceding computed tomography coronary angiography. Flow cytometry was performed to measure the osteocalcin-positive ( OCN +) CD 34+ KDR + and OCN + CD 34+ circulating endothelial progenitor cells ( EPCs ). Conventional early circulating EPCs CD 34+ CD 133+ KDR + was determined. Coronary calcification was defined as any Agatston score >0. 50% of patients (n=72/145) had coronary calcification. CRI score was associated with presence of coronary calcification ( P=0.004) (multivariable-adjusted: highest versus lowest quartile: odds ratio=5.6 [95% CI 1.1-28.9], P=0.041). Receiver operating characteristics curve revealed divergent behavior of OCN -expressing circulating EPCs ( OCN + CD 34+ EPCs : area under the curve=0.60, P=0.034; OCN + CD 34+ KDR + EPCs : area under the curve=0.59, P=0.053, positive predictors) versus conventional early EPCs ( CD 34+ CD 133+ KDR +: area under the curve=0.60, P=0.034, negative predictor) for coronary calcification, which persisted after multivariable adjustments ( OCN + CD 34+ KDR + [>75th percentile]: odds ratio=7.2 [95% CI 1.8-27.9], P=0.005; OCN + CD 34+ EPCs [>75th percentile]: odds ratio=6.0 [95% CI 1.5-23.3], P=0.010; CD 34+ CD 133+ KDR + [>75th percentile: odds ratio=0.3 [95% CI 0.1-1.0], P=0.053). Intriguingly, the CRI score was associated with increased OCN + CD 34+ EPCs (highest versus lowest quartile: B=+25.6 [95% CI 0.8-50.5] [×103/mL peripheral blood], P=0.043), but reduced CD 34+ CD 133+ KDR + EPCs (highest versus lowest quartile: B=-16.2 [95% CI -31.5 to -0.9], P=0.038). Conclusions Preceding 60 months of CRI is associated with increased risk of coronary calcification and altered OCN expression in circulating EPCs .

Osteogenic circulating endothelial progenitor cells are linked to electrocardiographic conduction abnormalities in rheumatic patients.

BACKGROUND: Osteogenic circulating endothelial progenitor cells (EPC) play a pathogenic role in cardiovascular system degeneration through promulgating vasculature calcification, but its role in conduction disorders as part of the cardiovascular degenerative continuum remained unknown. AIM: To investigate the role of osteocalcin (OCN)-expressing circulating EPCs in cardiac conduction disorders in the unique clinical sample of rheumatoid arthritis (RA) susceptible to both abnormal bone metabolism and cardiac conduction disorders. METHODS: We performed flow cytometry studies in 134 consecutive asymptomatic patients with rheumatoid arthritis to derive osteogenic circulating OCN-positive (OCN+) CD34+KDR+ vs. CD34+CD133+KDR+ conventional EPC. Study endpoint was the prespecified combined endpoint of electrocardiographic conduction abnormalities. RESULTS: Total prevalence of cardiac conduction abnormality was 9% (n = 12). All patients except one had normal sinus rhythm. One patient had atrial fibrillation. No patient had advanced atrioventricular (AV) block. Prevalence of first-degree heart block (>200 ms), widened QRS duration (>120 ms) and right bundle branch block were 6.7%, 2.1%, and 2.2% respectively. Circulating osteogenic OCN+ CD34+ KDR+ EPCs were significantly higher among patients with cardiac conduction abnormalities (p = 0.039). Elevated OCN+ CD34+ KDR+ EPCs> 75th percentile was associated with higher prevalence of cardiac conduction abnormalities (58.3% vs. 20.02%, p = 0.003). Adjusted for potential confounders, elevated OCN+ CD34+ KDR+ EPCs> 75th percentile remained independently associated with increased risk of cardiac conduction abnormalities (OR = 4.4 [95%CI 1.2-16.4], p = 0.028). No significant relation was found between conventional EPCs CD34+CD133+KDR+ and conduction abnormalities (p = 0.36). CONCLUSIONS: Elevated osteogenic OCN+ CD34+ KDR+ EPCs are independently associated with the presence of electrocardiographic conduction abnormalities in patients with rheumatoid arthritis, unveiling a potential novel pathophysiological mechanism.

Impact of obesity on longitudinal changes to cardiac structure and function in patients with Type 2 diabetes mellitus.

AIMS: Few prospective studies have evaluated the natural progression of left ventricular (LV) remodelling in patients with Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the impact of obesity on longitudinal cardiac structural and functional changes in patients with T2DM. METHODS AND RESULTS: This study comprised of 274 patients with T2DM (mean age, 62.2 ± 11.4 years; male, 51.5%). Echocardiographic parameters including LV geometry, systolic, and diastolic functions were measured at baseline and follow-up. The median follow-up was 24 months (from 12 months to 48 months). The entire cohort showed a significant increase in LV wall thickness, LV mass (LVM), and prevalence of concentric hypertrophy (19.6-27.3%). Further, systolic function and diastolic function had deteriorated at follow-up assessment. Multivariable adjusted linear regression demonstrated that baseline body mass index (BMI) predicted longitudinal change to LVM (ß = 0.29, P < 0.01) and LV ejection fraction (ß = -0.15, P < 0.05). Patients were divided into three groups according to their BMI: normal weight (BMI <23 kg/m2), overweight (BMI between 23 kg/m2 and 27.5 kg/m2), or obese (BMI ≥27.5 kg/m2). Importantly, obesity at baseline predicted a greater longitudinal increase in LVM and decrease in LV ejection fraction compared with overweight and normal weight patients. CONCLUSION: Being obese at baseline was associated with greater longitudinal increase in LV mass and greater deterioration in LV systolic function.

Prognostic Value of Hepatorenal Function By Modified Model for End-stage Liver Disease (MELD) Score in Patients Undergoing Tricuspid Annuloplasty.

BACKGROUND: The Model for End-stage Liver Disease excluding international normalized ratio (MELD-XI) score and the modified MELD score with albumin replacing international normalized ratio (MELD-Albumin) score, which reflect both liver and renal function, have been reported as predictors of adverse events in liver and heart disease. Nonetheless, their prognostic value in patients undergoing tricuspid annuloplasty has not been addressed. METHODS AND RESULTS: A total of 394 patients who underwent tricuspid annuloplasty were evaluated. Baseline clinical, laboratory, and echocardiographic parameters were recorded. Adverse outcome was defined as the occurrence of heart failure requiring admission or all-cause mortality. Patients who underwent tricuspid annuloplasty had a high prevalence of preoperative hepatorenal dysfunction that was more common in patients with severe tricuspid regurgitation than those with mild to moderate tricuspid regurgitation. The MELD-XI and MELD-Albumin scores were excellent predictors of 1-year adverse outcome (area under the curve: 0.69 and 0.75, respectively). Kaplan-Meier survival curve demonstrated that a high score on MELD-XI (≥12.0) and MELD-Albumin (≥10.7) was associated with an increased risk of adverse events. During a median follow-up of 40 months, both MELD-XI and MELD-Albumin scores were significantly associated with adverse outcome, even after adjusting for potential confounding factors. Significant improvement of hepatorenal function at 1 year postoperation was noted only in patients who had no adverse events, not in those who experienced an adverse outcome. CONCLUSIONS: Both MELD-XI score and MELD-Albumin score can provide useful information to predict adverse outcome in patients undergoing tricuspid annuloplasty. The present study supports monitoring of modified MELD score to improve preoperative risk stratification of these patients.