Search

Hypertrophic cardiomyopathy is an inherited cardiovascular disease, and 70% of patients have left ventricular outflow tract obstruction. Ventricular septal myectomy has been the gold standard treatment for most patients with refractory symptoms. Due to higher mortality associated with medical facilities with less experience, alcohol septal ablation has been accepted as an alternative to conventional surgical myectomy. It offers lower all-cause in-hospital complications and mortality, which could be potentially more preferable for patients with serious comorbidities. In recent years, radiofrequency ablation, providing another option with reproducibility and a low risk of permanent atrioventricular block, has become an effective invasive treatment to relieve left ventricular outflow tract obstruction. Moreover, substantial progress has been made in gene therapy for hypertrophic cardiomyopathy. The principal objective of this review is to present recent advances in non-pharmaceutical interventions in hypertrophic cardiomyopathy.

Sphingomyelin (SM) is one major phospholipids on lipoproteins. It is enriched on apolipoprotein B-containing particles, including very low-density lipoprotein (VLDL) and its catabolites, low-density lipoprotein (LDL). SM is synthesized by sphingomyelin synthase 1 and 2 (SMS1 and SMS2) which utilizes ceramide and phosphatidylcholine, as two substrates, to produce SM and diacylglyceride. SMS1 and SMS2 activities are co-expressed in all tested tissues, including the liver where VLDL is produced. Thus, neither Sms1 gene knockout (KO) nor Sms2 KO approach is sufficient to evaluate the effect of SMS on VLDL metabolism. We prepared liver-specific Sms1 KO/ global Sms2 KO mice to evaluate the effect of hepatocyte SM biosynthesis in lipoprotein metabolism. We found that hepatocyte total SMS depletion significantly reduces cellular sphingomyelin levels. Also, we found that the deficiency induces cellular glycosphingolipid levels which is specifically related with SMS1 but not SMS2 deficiency. To our surprise, hepatocyte total SMS deficiency has marginal effect on hepatocyte ceramide, diacylglyceride, and phosphatidylcholine levels. Importantly, total SMS deficiency decreases plasma triglyceride but not apoB levels and reduces larger VLDL concentration. The reduction of triglyceride levels also was observed when the animals were on a high fat diet. Our results show that hepatocyte total SMS blocking can reduce VLDL-triglyceride production and plasma triglyceride levels. This phenomenon could be related with a reduction of atherogenicity.

Diabetic nephropathy (DN) is the major cause of chronic kidney disease and end-stage renal disease. Previous studies have demonstrated that long-chain omega-3 polyunsaturated fatty acids (PUFAs) might have therapeutic potential in reducing proteinuria in DN. However, the local level of eicosanoids derived from PUFAs in the plasma of DN patients remains unclear. This work aims to study the eicosanoid profile difference in plasma of DN patients and type 2 diabetes (T2D) without DN. A total of 27 T2D patients with similar diabetic duration were recruited and divided into T2D+DN group and T2D+NDN (non-DN) group based on urinary albumin excretion (UAE) detection. Using LC-MS/MS-based metabolomics, DN patients showed increased level of lipoxygenase (LOX) metabolites (5-HETE and LTB4) and decreased levels of eicosanoids derived according to the cytochrome P450s (CYP450) metabolic pathway (5,6-DHET; 14,15-DHET and 9,10-diHOME). Receiver operating characteristics and logistic regression analysis revealed increased level LOX metabolites and decreased level of CYP450 metabolites were significantly correlated with the incidence of DN in T2D patients. LOX and CYP450 metabolites correlated with DN incidence in T2D patients, which might be treatment targets for DN in T2D patients.

OBJECTIVE This study aimed to comprehensively assess the characteristics and risk factors of hyperthyroidism with pulmonary hypertension (PH). METHODS This was a retrospective cross-sectional analysis of 315 consecutive patients with hyperthyroidism admitted to the endocrinology department of Tongji Hospital from February 2016 to December 2017. PH was defined as a pulmonary arterial systolic pressure above 35 mm Hg measured by echocardiography. RESULTS Among the 315 patients, 208 were females, the median age was 42 (30-51) years, and the median disease duration was 12 (3-48) months. Thirty-five percent (111/315) of patients were identified with PH. Patients with hyperthyroidism and PH showed significantly higher serum concentrations of free thyroxine (FT4), free triiodothyronine, thyroid receptor antibodies, total bilirubin (TB), direct and indirect bilirubin, lower serum levels of hemoglobin and creatinine, and more severe cardiac load (P < .05 for each) compared with patients without PH. Levels of serum FT4, free triiodothyronine, thyroid receptor antibodies, and thyroid peroxidase antibody were different among groups of patients with different levels of pulmonary arterial systolic pressure (P < .05 for each). Multivariate logistic regression analysis indicated that serum FT4 (odds ratio, 1.02; 95% CI, 1.01-1.04; P = .004) and TB (OR, 1.03; 95% CI, 1.00-1.06; P = .030) were independent risk factors for PH in patients with hyperthyroidism. CONCLUSION Elevated serum FT4 and TB levels may be independent risk factors for PH in patients with hyperthyroidism and valuable indicators for the identification and treatment of patients with PH and hyperthyroidism.

Background Strong epidemiologic evidence indicates that green tea intake is protective against hyperlipidemia; however, randomized controlled studies have presented varying results. In the present study, we aimed to conduct a literature review and meta-analysis to assess the effect of green tea on blood lipids. Methods PubMed, Embase, and the Cochrane Library were electronically explored from inception to September 2019 for all relevant studies. Random effect models were used to estimate blood lipid changes between green tea supplementation and control groups by evaluating the weighted mean differences (WMD) with 95% confidence intervals (CIs). The risk of bias for study was assessed using the Cochrane tool. Publication bias was evaluated using funnel plots and Egger’s tests. Results Thirty-one trials with a total of 3321 subjects were included in the meta-analysis. In general, green tea intake significantly lowered the total cholesterol (TC); WMD: − 4.66 mg/dL; 95% CI: − 6.36, − 2.96 mg/dL; P P P = 0.15). In addition, significant publication bias from funnel plots or Egger’s tests was not evident. Conclusions Collectively, consumption of green tea lowers LDL cholesterol and TC, but not HDL cholesterol or triglycerides in both normal weight subjects and those who were overweight/obese; however, additional well-designed studies that include more diverse populations and longer duration are warranted.

Background The results of human clinical trials investigating the effects of green tea on glycemic control are inconsistent. Methods We conducted a systematic review and meta-analysis of RCTs that examined the effects of green tea supplementation on glycemic control. A literature search in PubMed, Embase, and Cochrane Library databases for RCTs that investigated the effect of green tea consumption on glycemic control was performed up to February 2020. A random-effects model was used to estimate weighted mean difference (WMD) with 95% confidence intervals (CIs). Results Twenty-seven trials involving 2194 subjects were included in the meta-analysis. The pooled results showed that green tea significantly lowered fasting blood glucose by − 1.44 mg/dL (95%CI:-2.26, − 0.62 mg/dL; P I2 = 7.7%). However, green tea consumption did not significantly affect fasting insulin and HbA1c values. The mean differences were − 0.46μIU/mL (95% CI: − 1.10, 0.17μIU/mL; P = 0.21) for fasting insulin and − 0.06%; (95% CI: − 0.12, 0.01%; P = 0.07) for HbA1c concentrations. Heterogeneity was significant in fasting insulin (I2 = 46.8%) and mild in HbA1c (I2 = 1.7%). Conclusions In short-term trials, green tea supplementation significantly reduced fasting glucose, but had no significant effect on fasting insulin and HbA1c. Long-term trials assessing the effects of green tea supplementation on glycemic control are needed.

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. However, this procedure remains complex and time-consuming, and the recurrence of AF after PVI is still unsatisfactory. Current technologies have improved our knowledge of the association between radiofrequency lesion creation and ablation parameters (power and duration), which triggered the development of high-power short-duration (HPSD). During the past decade, several preclinical and clinical studies have been conducted to confirm the feasibility, safety, and outcome of PVI ablation with HPSD or very high-power short-duration (vHPSD) settings, which increased electrophysiologists' interests in the utility of HPSD strategies. This paper describes the theoretical basis and recent research findings of HPSD or vHPSD ablation and summarizes the state-of-the-art evidence behind the role of this strategy in PVI.

Background: Although evidence from animal and observational studies has supported the beneficial effects of green tea intake for lowering blood pressure (BP), randomized placebo-controlled trials (RCTs) have yielded conflicting results. In this meta-analysis of RCTs, we aimed to assess the effects of green tea supplementation on measures of BP control. Methods: The PubMed, Embase, and Cochrane Library databases were electronically searched from inception to August 2019 for all relevant studies. The results were pooled using the generic inverse-variance method with random-effects weighting and expressed as mean differences (MDs) with 95% confidence intervals (CIs). The quality of studies was assessed using the Jadad score. Publication bias was evaluated using funnel plots, Egger test, and Begg test. Results: Twenty-four trials with 1697 subjects were included in the meta-analysis. The pooled results showed that green tea significantly lowered systolic BP (SBP; MD: −1.17 mm Hg; 95%CI: −2.18 to −0.16mm Hg; P = .02) and diastolic BP (DBP; MD: −1.24 mm Hg; 95%CI:−2.07 to −0.40mm Hg; P = .004). Significant heterogeneity was found for both SBP (I2 = 43%) and DBP (I2 = 57%). In addition, no evidence of significant publication bias was found from funnel plots or Egger test (P = .674 and P = .270 for SBP and DBP, respectively). Conclusion: Overall, green tea significantly reduced SBP and DBP over the duration of the short-term trials. Larger and longer-term trials are needed to further investigate the effects of green tea supplementation on BP control and clinical events.

Data regarding the efficacy and safety of zero or near-zero fluoroscopic ablation of cardiac arrhythmias are limited. A literature search was conducted using PubMed and Embase for relevant studies through January 2016. Ten studies involving 2,261 patients were identified. Compared with conventional radiofrequency ablation method, zero or near-zero fluoroscopy ablation significantly showed reduced fluoroscopic time (standard mean difference [SMD] -1.62, 95% CI -2.20 to -1.05; p0.00001), ablation time (SMD -0.16, 95% CI -0.29 to -0.04; p = 0.01), and radiation dose (SMD -1.94, 95% CI -3.37 to -0.51; p = 0.008). In contrast, procedure duration was not significantly different from that of conventional radiofrequency ablation (SMD -0.03, 95% CI -0.16 to 0.09; p = 0.58). There were no significant differences between both groups in immediate success rate (odds ratio [OR] 0.99, 95% CI 0.49 to 2.01; p = 0.99), long-term success rate (OR 1.13, 95% CI 0.42 to 3.02; p = 0.81), complication rates (OR 0.98, 95% CI 0.49 to 1.96; p = 0.95), and recurrence rates (OR 1.29, 95% CI 0.74 to 2.24; p = 0.37). In conclusion, radiation was significantly reduced in the zero or near-zero fluoroscopy ablation groups without compromising efficacy and safety.

A systematic review and meta-analysis were conducted to evaluate the diagnostic accuracy of substantia nigra hyper-echogenicity by transcranial sonography (TCS) for the diagnosis of Parkinson's disease (PD). PubMed, Embase and the Cochrane Library were electronically searched from inception to June 2018 for all relevant studies. The methodological quality of each study was evaluated by two independent reviewers, who used the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Articles reporting information sufficient to calculate the sensitivity and specificity of TCS to diagnose PD were included. Statistical analysis included data pooling, heterogeneity testing, sensitivity analyses and forest meta-regression. Thirty-nine studies (3123 participants with PD) were analyzed. The pooled sensitivity and specificity of TCS were 0.84 (95% confidence interval: 0.81-0.87) and 0.85 (0.80-0.88), respectively, for differentiating PD from normal controls or participants with other parkinsonian syndromes. In the secondary outcome, PD participants exhibited a significant increase in substantia nigra areas than either normal controls (0.14 [0.12-0.16], p0.0001) or participants with other parkinsonian syndromes (0.11 [0.08-0.13], p0.0001). This meta-analysis revealed the high diagnostic performance of TCS in differentiating patients with PD from both normal controls and participants with other parkinsonian syndromes.

Background Conflicting results have been obtained in trials that have evaluated the prophylactic efficacy of N ‐acetylcysteine ( NAC ) pretreatment in the prevention of contrast‐induced nephropathy ( CIN ). In this meta‐analysis of randomized controlled trials, we aimed to assess the effectiveness of NAC treatment for the prevention of CIN . Methods and Results PubMed, EMBASE , and the Cochrane Library were electronically searched from inception to January 2016 for all relevant studies. The weighted relative risk ( RR ) and corresponding 95% CI for incident CIN were estimated using random effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. The study included 11 480 participants and 1653 cases of CIN . The incidence of CIN was 12.8% in the NAC group versus 16.0% in the control group ( RR : 0.76, 95% CI : 0.66–0.88, P =0.0002). In the patients undergoing coronary angiography, the incidence of CIN in the NAC group versus the control group was 13.7% versus 17.2% ( RR : 0.74, 95% CI : 0.63–0.87, P =0.0002); in those undergoing peripheral angiography, the incidence was 6.4% versus 5.8% ( RR : 1.00, 95% CI : 0.42–2.40, P =1.00); in those undergoing computed tomography, the incidence was 7.7% versus 14.8% ( RR : 0.51, 95% CI : 0.29–0.89, P =0.02). Conclusions Our meta‐analysis showed an inverse and significant association between NAC supplementation and risk of CIN in patients undergoing coronary angiography and computed tomography, while a protective role for NAC in patients undergoing peripheral angiography was not obvious.

Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, antiapoptotic, and antioxidatant effects, and cardiovascular protection. Liver has abundant epoxygenase expression and high levels of EET production; however, the roles of epoxygenases in liver diseases remain to be elucidated. In this study, we investigated the protection against high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in mice with endothelial-specific CYP2J2 overexpression (Tie2-CYP2J2-Tr). After 24 wk of high-fat diet, Tie2-CYP2J2-Tr mice displayed attenuated NAFLD compared with controls. Tie2-CYP2J2-Tr mice showed significantly decreased plasma triglyceride levels and liver lipid accumulation, improved liver function, reduced inflammatory responses, and less increase in hepatic oxidative stress than wild-type control mice. These effects were associated with inhibition of NF-κB/JNK signaling pathway activation and enhancement of the antioxidant defense system in Tie2-CYP2J2-Tr mice in vivo. We also demonstrated that 14,15-EET treatment protected HepG2 cells against palmitic acid-induced inflammation and oxidative stress. 14,15-EET attenuated palmitic acid-induced changes in NF-κB/JNK signaling pathways, malondialdehyde generation, glutathione levels, reactive oxygen species production, and NADPH oxidase and antioxidant enzyme expression in HepG2 cells in vitro. Together, these results highlight a new role for CYP epoxygenase-derived EETs in lipotoxicity-related inflammation and oxidative stress and reveal a new molecular mechanism underlying EETs-mediated anti-inflammatory and antioxidant effects that could aid in the design of new therapies for the prevention and treatment of NAFLD.

We conducted a meta-analysis to assess the association between patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) and its subtypes simple steatosis(SS) and nonalcoholic steatohepatitis (NASH). The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models, with assessment for heterogeneity and publication bias. Twenty-three case-control studies involving 6071 NAFLD patients and 10366 controls were identified. The combined results showed a significant association between NAFLD risk and the rs738409 polymorphism in all genetic models (additive model: OR = 3.41, 95% CI = 2.57–4.52; P < 0.00001). In addition, evidence indicated that the rs738409 polymorphism was significantly associated with NASH in all genetic models (additive model: OR = 4.44, 95% CI = 3.39–5.82; P < 0.00001). The subgroup and sensitivity analyses showed that these changes were not influenced by the ethnicities and ages of subjects or by the source of controls. The rs738409 polymorphism was only significantly associated with risk of simple steatosis in the allele contrast and had no effect in the other genetic models. These findings suggest that the rs738409 polymorphism in PNPLA3 gene confers high cross-ethnicity risk for NAFLD and NASH development.

Observational studies have revealed that higher serum vitamin E concentrations and increased vitamin E intake and vitamin E supplementation are associated with beneficial effects on glycaemic control in type 2 diabetes mellitus (T2DM). However, whether vitamin E supplementation exerts a definitive effect on glycaemic control remains unclear. This article involves a meta-analysis of randomised controlled trials of vitamin E to better characterise its impact on HbA1c, fasting glucose and fasting insulin. PubMed, EMBASE and the Cochrane Library were electronically searched from the earliest possible date through April 2013 for all relevant studies. Weighted mean difference (WMD) was calculated for net changes using fixed-effects or random-effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. Fourteen randomised controlled trials involving individual data on 714 subjects were collected in this meta-analysis. Increased vitamin E supplementation did not result in significant benefits in glycaemic control as measured by reductions in HbA1c, fasting glucose and fasting insulin. Subgroup analyses revealed a significant reduction in HbA1c (−0.58%, 95% CI −0.83 to −0.34) and fasting insulin (−9.0 pmol/l, 95% CI −15.90 to −2.10) compared with controls in patients with low baseline vitamin E status. Subgroup analyses also demonstrated that the outcomes may have been influenced by the vitamin E dosage, study duration, ethnic group, serum HbA1c concentration, and fasting glucose control status. In conclusion, there is currently insufficient evidence to support a potential beneficial effect of vitamin E supplementation on improvements of HbA1c and fasting glucose and insulin concentrations in subjects with T2DM.

Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active cis-epoxyeicosatrienoic acids, which have potent vasodilatory, antiinflammatory, antiapoptotic, and antidiabetes properties. Here, we showed the effects of cardiac-specific overexpression of CYP epoxygenase 2J2 (CYP2J2) on diabetic cardiomyopathy and insulin resistance in high-fat (HF) diet fed, low-dose streptozotocin-treated mice. Diabetic cardiomyopathy was induced by HF and streptozotocin in cardiac-specific CYP2J2 transgenic mice. Physiological parameters and systemic metabolic parameters were monitored using ELISA kits. Intraperitoneal injection glucose tolerance test and hyperinsulinemic-euglycemic clamp study were implied to indicate insulin resistance. Cardiac function was assessed by echocardiography and Millar catheter system. Real-time PCR and Western blotting were used in signal pathway detection. αMHC-CYP2J2 transgenic mice showed significantly lower plasma glucose and insulin levels, improved glucose tolerance, and increased cardiac glucose uptake. Furthermore, αMHC-CYP2J2 transgenic mice were significantly protected from HF-streptozotocin-induced diabetic cardiomyopathy. Strikingly, CYP2J2 overexpression attenuated myocardial hypertrophy induced by diabetes. We conclude that cardiac-specific overexpression of CYP2J2 significantly protects against diabetic cardiomyopathy, which may be due to improved cardiac insulin resistance, glucose uptake, and reversal of cardiac hypertrophy. Relevant mechanisms may include up-regulation of peroxisome proliferator-activated receptor γ, activation of insulin receptor and AMP-activated protein kinase signaling pathways, and inhibition of nuclear factor of activated T cells c3 signal by enhanced atrial natriuretic peptide production. These results suggest that CYP2J2 epoxygenase metabolites likely play an important role in plasma glucose homeostasis, and enhancement of epoxyeicosatrienoic acids activation may serve as an effective therapeutic strategy to prevent diabetic cardiomyopathy.

Background Cardiac arrhythmias can occur during pregnancy. Owing to radiation exposure and other uncertain risks for the mother and fetus, catheter ablation has rarely been performed and is often delayed until the postpartum period. We reported 2 pregnant women who were experiencing severe arrhythmias and were successfully ablated without fluoroscopic guidance. We also carried out a literature review of cases of pregnant women who underwent zero-fluoroscopy ablation. Methods and results One woman had drug-resistant and poorly tolerated frequent premature ventricular contraction (PVC) and ventricular tachycardia (VT). The other one had persistent and hardly terminated supraventricular tachycardia (SVT) via a right accessory pathway. The 2 patients were successfully underwent zero-fluoroscopy ablation guided by Ensite NavX system. The procedure time was 42 and 71 minutes, respectively. Conclusion Catheter ablation of SVT or PVC/VT in pregnant patients can be safely and effectively performed with a completely zero-fluoroscopy approach guided by the Ensite NavX system. In the case of a drug refractory, life-threatening arrhythmia during pregnancy, catheter ablation may be considered.

Cytochrome P-450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important roles in regulating cardiovascular functions. The anti-inflammatory, antiapoptotic, proangiogenic, and antihypertensive properties of EETs suggest a beneficial role for EETs in diabetic nephropathy. Endogenous EET levels are maintained by a balance between synthesis by CYP epoxygenases and hydrolysis by epoxide hydrolases into physiologically less active dihydroxyeicosatrienoic acids. Genetic disruption of soluble epoxide hydrolase (sEH/EPHX2) results in increased EET levels through decreased hydrolysis. This study investigated the effects of sEH gene disruption on diabetic nephropathy in streptozotocin-induced diabetic mice. Streptozotocin-induced diabetic manifestations were attenuated in sEH-deficient mice relative to wild-type controls, with significantly decreased levels of Hb A1c, creatinine, and blood urea nitrogen and urinary microalbumin excretion. The sEH-deficient diabetic mice also had decreased renal tubular apoptosis that coincided with increased levels of antiapoptotic Bcl-2 and Bcl-xl, and decreased levels of the proapoptotic Bax. These effects were associated with activation of the PI3K-Akt-NOS3 and AMPK signaling cascades. sEH gene inhibition and exogenous EETs significantly protected HK-2 cells from TNFα-induced apoptosis in vitro. These findings highlight the beneficial role of the CYP epoxygenase-EETs-sEH system in the pathogenesis of diabetic nephropathy and suggest that the sEH inhibitors available may be potential therapeutic agents for this condition.

Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important and diverse roles in the cardiovascular system. The anti-inflammatory, anti-apoptotic, pro-angiogenic, and anti-hypertensive properties of EETs in the cardiovascular system suggest a beneficial role for EETs in diabetic nephropathy. This study investigated the effects of endothelial specific overexpression of the CYP2J2 epoxygenase on diabetic nephropathy in streptozotocin induced diabetic mice. Endothelial CYP2J2 overexpression attenuated renal damage as measured by urinary microalbumin and glomerulosclerosis. These effects were associated with inhibition of TGF-β/Smad signaling in the kidney. Indeed, overexpression of CYP2J2 prevented TGF-β1 induced renal tubular epithelial-mesenchymal transition in vitro. These findings highlight the bene cial roles of the CYP epoxygenase-EET system in the pathogenesis of diabetic nephropathy.