The effect of high-power short-duration pulmonary vein isolation on PWPT-a predictor of paroxysmal atrial fibrillation.

BACKGROUND: The P wave peak time (PWPT) is a predictor of paroxysmal atrial fibrillation (PAF). High-power short-duration ablation has been associated with improved durability of circumferential pulmonary vein electrical isolation (PVI). We investigated the effect of high-power short-duration PVI on PWPT in patients with PAF. METHODS: Out of 111 patients with PAF, 91 received radiofrequency ablation (ablation group) and 20 received medication treatment (control group). A VIZIGO sheath and an STSF catheter (Biosense Webster, CA, USA) were used together for high-power short-duration circumferential PVI at ablation index values of 500 and 400 for the anterior and posterior walls, respectively. The patients were followed up for 12 months. RESULTS: The preoperative PWPT in the ablation group was similar to that in the control group: PWPT II = 54.38 ± 6.18 ms vs. 54.35 ± 6.12 ms (p > 0.05), PWPT V1 = 54.19 ± 6.21 ms vs. 54.31 ± 6.08 ms (p > 0.05), respectively. Circumferential PVI was achieved for all patients in the ablation group during the operation. At the 12-month follow-up, there were seven cases of AF recurrence. The PWPT in the ablation group 12 months postoperatively was shorter than the preoperative value: PWPT II = 49.39 ± 7.11 ms vs. 54.38 ± 6.18 ms (p < 0.001), PWPT V1 = 47.69 ± 7.01 ms vs. 54.19 ± 6.21 ms (p < 0.001). The PWPT in the patients with AF recurrence was significantly longer than that in the non-recurrence patients: PWPT II = 50.48 ± 7.12 ms vs. 47.33 ± 6.21 ms (p < 0.001), PWPT V1 = 50.84 ± 7.05 ms vs. 47.19 ± 6.27 ms, (p < 0.001). The PWPT of the control group at the 12-month follow-up was similar to the baseline level: PWPT II = 54.32 ± 6.20 ms vs. 54.35 ± 6.12 ms (p > 0.05), PWPT V1 = 53.89 ± 6.01 ms vs. 54.31 ± 6.08 ms (p > 0.05). CONCLUSION: The results showed that high-power short-duration PVI had a positive effect on PWPT, which is a predictor of PAF.

Translocation of gasdermin D induced mitochondrial injury and mitophagy mediated quality control in lipopolysaccharide related cardiomyocyte injury.

BACKGROUNDS: Inflammation underlies the mechanism of different kinds of heart disease. Cytoplasmic membrane localized N-terminal fragment of gasdermin-D (GSDMD-N) could induce inflammatory injury to cardiomyocyte. However, effects and dynamic changes of GSDMD during the process of lipopolysaccharide (LPS) related inflammatory stress induced cardiomyocyte injury are barely elucidated to date. In this study, LPS related cardiomyocyte injury was investigated based on potential interaction of GSDMD-N induced mitochondrial injury and mitophagy mediated mitochondria quality control. METHODS: HL-1 cardiomyocytes were treated with LPS and Nigericin to induce inflammatory stress. The dual-fluorescence-labelled GSDMD expressed HL-1 cardiomyocytes were constructed to study the translocation of GSDMD. The mitochondrial membrane potential (MMP) was measured by JC-1 staining. Mitophagy and autophagic flux were recorded by transmission electron microscopy and fluorescent image. RESULTS: GSDMD-N showed a time-dependent pattern of translocation from mitochondria to cytoplasmic membrane under LPS and Nigericin induced inflammatory stress in HL-1 cardiomyocytes. GSDMD-N preferred to localize to mitochondria to permeablize its membrane and dissipate the MMP. This effect couldn't be reversed by cyclosporine-A (mPTP inhibitor), indicating GSDMD-N pores as alternative mechanism underlying MMP regulation, in addition to mitochondrial permeability transition pore (mPTP). Moreover, the combination between GSDMD-N and autophagy related Microtubule Associated Protein 1 Light Chain 3 Beta (LC3B) was verified by co-immunoprecipitation. Besides, mitophagy alleviating GSDMD-N induced mitochondrial injury was proved by pre-treatment of autophagy antagonist or agonist in GSDMD-knock out or GSDMD-overexpression cells. A time-dependent pattern of GSDMD translocation and mitochondrial GSDMD targeted mitophagy were verified. CONCLUSION: Herein, our study confirmed a crosstalk between GSDMD-N induced mitochondrial injury and mitophagy mediated mitochondria quality control during LPS related inflammation induced cardiomyocyte injury, which potentially facilitating the development of therapeutic target to myocardial inflammatory disease. Our findings support pharmaceutical intervention on enhancing autophagy or inhibiting GSDMD as potential target for inflammatory heart disease treatment.

Role of the Gut Microbiota in Glucose Metabolism During Heart Failure.

Background: Blood glucose disorders are prevalent in heart failure, while the influence of the gut microbiota on this process remains unclear. Here, we used heart failure model mice and fecal microbiota transplantation (FMT) mice to evaluate the effect of the gut microbiota on the regulation of blood glucose during heart failure. Methods: Thoracic aortic constriction (TAC) surgery was performed in a heart failure model, while an antibiotic cocktail was used to eliminate the microbiota to establish a germ-free (GF) model. Blood glucose, insulin, and glucagon levels were measured, and an intraperitoneal glucose tolerance test (IPGTT) was performed. 16S rRNA sequencing and metabolomics were used to evaluate the changes in gut microbiota structure and metabolism induced by TAC. Another group of FMT mice was established to observe the effect of the gut microbiota on host metabolism. Results: After microbiota clearance, the glucagon concentration, the homeostasis model assessment for insulin resistance (HOMA-IR), and the area under the curve (AUC) of the IPGTT were decreased significantly in the TAC germ-free (TAC-GF) group in the third month as compared to the other groups. 16S rRNA sequencing indicated that TAC surgery affected the gut microbiota structure, and fecal metabolomics suggested that noradrenaline and adrenaline levels were higher in the TAC group than in the sham group. The FMT mice transplanted with the feces of the TAC (FMT-TAC) mice displayed a higher AUC of IPGTT, accompanied by a higher glucagon level, insulin level, and HOMA-IR than those of the mice in the other groups. The serum metabolomics of the FMT-TAC group showed that noradrenaline levels were significantly higher than those of the FMT-sham group. Conclusion: The gut microbiota and its metabolism were altered during heart failure, which increased blood glucose and glucagon in the host.

Early renal impairment is associated with in-hospital death of patients with COVID-19.

INTRODUCTION: Renal impairment is a common complication in coronavirus disease 2019 (COVID-19), although its prognostic significance remains unknown. OBJECTIVES: This study determines the impact of early renal impairment on the clinical outcome of COVID-19. METHODS: Patients diagnosed with COVID-19 and hospitalized in Xiaogan Central Hospital from 20 January to 29 February 2020 were retrospectively included and grouped into two cohorts (cohort with normal renal function and cohort with renal insufficiency) based on the renal function detected on admission. Records of clinical manifestation, laboratory findings and clinical outcome were collected and compared between these two cohorts. RESULTS: A total 543 COVID-19 patients were included. Among these patients, 70 patients developed early renal impairment, with an incidence of 12.89%. A significantly higher white blood cell (WBC) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatine (Cr), blood urine nitrogen (BUN) and brain natriuretic peptide (BNP) and a significantly lower blood platelet (PLT), lymphocyte count, prealbumin and albumin (ALB) were detected in the cohort with renal insufficiency (P < 0.05). Patients with early renal impairment were also associated with higher incidences of haematuria/proteinuria, higher incidences of mortality and prolonged hospitalization duration. The independent risk factors for in-hospital death included age >65 years old, complication of diabetes, renal impairment on admission (Cr > 73 µmol/L and eGFR < 60 ml/min 1.73 m2 ), WBC > 9.5 × 109 /L and ALB < 35 g/L. CONCLUSION: Early renal impairment is associated with higher risk of in-hospital death for patients with COVID-19. Risk stratification according to renal function can better guide the clinical management of COVID-19.

Risk factors of pacing dependence and cardiac dysfunction in patients with permanent pacemaker implantation.

AIMS: Right ventricular pacing (RVP) dependence could impair left ventricular ejection fraction (LVEF). This study aimed to illuminate the relationship between RVP proportion and LVEF, as well as disclosing independent predictors of RVP dependence. METHODS AND RESULTS: Patients indicated for permanent pacemaker implantation were included (2016-2020). The ventricular pacing lead was placed in right ventricular apex or septum. Pacing mode programming followed universal standard. Electrocardiographic, echocardiographic, and serological parameters were collected. RVP dependence was defined according to its influence on LVEF. This study was of case-control design. Included patients were matched by potentially confounding factors through propensity score matching. A total of 1183 patients were included, and the mean duration of follow-up was 24 months. Percentage of RVP < 80% hardly influenced LVEF; however, LVEF tended to decrease with higher RVP proportion. High degree/complete atrioventricular block (AVB) [odds ratio (OR) = 5.71, 95% confidence interval (CI): 3.66-8.85], atrial fibrillation (AF) (OR = 2.04, 95% CI: 1.47-2.82), percutaneous coronary intervention (PCI) (OR = 2.89, 95% CI: 1.24-6.76), maximum heart rate (HRmax ) < 110 b.p.m. (OR = 2.74, 95% CI: 1.58-4.76), QRS duration > 120 ms (OR = 2.46, 95% CI: 1.42-4.27), QTc interval > 470 ms (OR = 2.01, 95% CI: 1.33-3.05), and pulmonary artery systolic pressure (PASP) > 40 mmHg (OR = 1.93, 95% CI: 1.46-2.56) were proved to predict RVP dependence. CONCLUSIONS: High RVP percentage (>80%) indicating RVP dependence significantly correlates with poor prognosis of cardiac function. High degree/complete AVB, AF, ischaemic aetiology, PCI history, HRmax  < 110 b.p.m., QRS duration > 120 ms, QTc interval > 470 ms, and PASP > 40 mmHg were verified as independent risk factors of RVP dependence.

Application of isoxanthopterin as a new pterin marker in the differential diagnosis of hyperphenylalaninemia.

BACKGROUND: This study aimed to explore the value of applying a new pterin marker (isoxanthopterin) to the traditional urine pterin analysis to reduce the rate of mis-diagnosis of 6-pyruvoyltetrahydropterin synthase deficiency (PTPSD) and improve the accuracy of diagnosis. METHODS: We compared the urine neopterin (N), biopterin (B), isoxanthopterin (Iso), B% and Iso% levels between patients with phenylalanine hydroxylase deficiency and those with PTPSD, and found the most specific pterin biomarkers by ROC analysis. A positive cut-off value of urine pterins was determined. The effect of combined Iso% + B + B% in reducing PTPSD mis-diagnosis was evaluated, and the different urine pterin levels in PTPSD and false PTPSD (FPTPSD) were compared. The concordance of PTPSD diagnosis by the new pterin scheme and gene mutation analysis was determined. RESULTS: (1) Urinary B, B%, Iso and Iso% were significantly lower in PTPSD than those in phenylalanine hydroxylase-deficiency group (P < 0.01); (2) Iso%, B%, and B were the most specific markers; (3) The positive cut-off values of B, B%, Iso% for PTPSD were < 0.17 mmoL/moLCr, < 5.0%, and < 9.5%, respectively; (4) urinary B + B% + Iso% scheme significantly reduced the false-positive rate of PTPSD compared to traditional ones. The Iso% levels in FPTPSD group were higher than the ones in PTPSD group; (5) an accuracy of diagnosis for PTPSD was increased by 9-19% when Iso% was introduced to urinary pterin scheme. CONCLUSIONS: Iso% is helpful to reduce the rate of misdiagnosis of PTPSD in the diagnosis by urinary pterin analysis for hyperphenylalaninemias and improve the accuracy of diagnosis. This approach is worthy of further development and increased utilization.

Influence of the Right Ventricular Lead Location on Ventricular Arrhythmias in Cardiac Resynchronization Therapy.

BACKGROUND: The influence of different right ventricular lead locations on ventricular arrhythmias (VTA) in patients with a cardiac resynchronization therapy (CRT) is not clear. This study aimed to evaluate the influence on VTA in patients with a CRT when right ventricular lead was positioned at the right ventricular middle septum (RVMS) and the right ventricular apical (RVA). METHODS: A total of 352 patients implanted with a CRT-defibrillator (CRT-D) between May 2012 and July 2016 in the Department of Cardiology of Anhui Provincial Hospital were included. Two-year clinical and pacemaker follow-up data were collected to evaluate the influence of the right ventricular lead location on VTA. Patients were divided into the RVMS group (n = 155) and the RVA group (n = 197) based on the right ventricular lead position. The VTA were compared between these two groups using a Kaplan-Meier curve and Cox multivariate analysis. RESULTS: When the left ventricular lead location was not considered, RVMS and RVA locations did not affect VTA. However, the subgroup analysis results showed that when the left ventricular lead was positioned at the anterolateral cardiac vein (ALCV), the RVMS group had an increased risk of ventricular arrhythmias and appropriate defibrillation (hazard ratio [HR] = 3.29, P = 0.01 and HR = 4.33, P < 0.01, respectively); when the left ventricular lead was at the posterolateral cardiac vein (PLCV), these risks in the RVMS group decreased (HR = 0.45, P = 0.02 and HR = 0.33, P < 0.01, respectively), and when the left ventricular lead was at the lateral cardiac vein, there was no difference between the two groups. In regard to inappropriate defibrillation, there was no significant difference among all these groups. CONCLUSIONS: When the left ventricular lead was positioned at ALCV or PLCV, the right ventricular lead location was associated with VTA and appropriate defibrillation after CRT. Greater distances between leads not only improved cardiac function but also may reduce the risk of VTA.

QDPR gene mutation and clinical follow-up in Chinese patients with dihydropteridine reductase deficiency.

BACKGROUND: This study aimed to investigate the mutation spectrum of the QDPR gene, to determine the effect of mutations on dihydropteridine reductase (DHPR) structure/function, to discuss the potential genotypephenotype correlation, and to evaluate the clinical outcome of Chinese patients after treatment. METHODS: Nine DHPR-deficient patients were enrolled in this study and seven of them underwent neonatal screening. QDPR gene mutations were analyzed and confirmed by routine methods. The potential pathogenicity of missense variants was analyzed using Clustal X, PolyPhen program and Swiss-PDB Viewer 4.04_OSX software, respectively. The clinical outcomes of the patients were evaluated after long-term treatment. RESULTS: In 10 mutations of the 9 patients, 4 were novel mutations (G20V, V86D, G130S and A175R), 4 were reported by us previously, and 2 known mutations were identified. R221X was a hotspot mutation (27.7%) in our patients. Eight missense mutations probably had damage to protein. Six patients in this series were treated with a good control of phenylalanine level. The height and weight of the patients were normal at the age of 4 months to 7.5 years. Four patients, who underwent a neonatal screening and were treated early, showed a normal mental development. In 2 patients diagnosed late, neurological symptoms were significantly improved. CONCLUSIONS: The mutation spectrum of the QDPR gene is different in the Chinese population. Most mutations are related to severe phenotype. The determination of DHPR activity should be performed in patients with hyperphenylalaninemia. DHPR-deficient patients who were treated below the age of 2 months may have a near normal mental development.

Pathogens promote matrilocal family ties and the copying of foreign religions.

Within the same pathogen-stress framework as proposed by Fincher & Thornhill (F&T), we argue further that pathogen stress promotes matrilocal rather than patrilocal family ties which, in turn, slow down the process of modernity; and that pathogen stress promotes social learning or copying, including the adoption of foreign religions.

Effects of ankle stabilizers on electromyographic activities of lower extremity muscles during simulated half-squat parachute landing / 医用生物力学

Objective To study effects of ankle stabilizer on electromyographic activities of lower extremity muscles during the simulated half squat parachute landing and its gender differences. Method Eight male and eight female healthy adults were required to jump from a platform of 0.72 m high to simulate half squat parachute landing. The experiment was divided into 3 groups: the barefoot one as control group, the group wearing tapes and braces respectively. The electromyogram (EMG) of each subject’s tibial anterior, lateral gastrocnemius, biceps femoralis and rectus femoralis was measured. Two way ANOVA was used to analyze and evaluate the effect of the stabilizers and genders on EMG variables. Results The use of brace significantly increased the pre landing EMG amplitude of the tibialis anterior for male (Control: 266 μV; Tape: 368 μV; Brace: 552 μV). The stabilizers had no significant effects on the other EMG parameters. Conclusions Semi rigid ankle braces are capable of arousing more active EMG of male’s ankle flexor during half squat parachute landing, but female does not share this predominance. Ankle stabilizers have no significant effects on EMG activities for knee joints.