Inverse-designed counter-tapered coupler based broadband and compact silicon mode multiplexer/demultiplexer.

A mode multiplexer/demultiplexer (MUX/DeMUX) is a crucial component for constructing mode-division multiplexing (MDM) systems. In this paper, we propose and experimentally demonstrate a wide-bandwidth and highly-integrated mode MUX/DeMUX based on an inverse-designed counter-tapered coupler. By introducing a functional region composed of subunits, efficient mode conversion and evolution can be achieved, greatly improving the mode conversion efficiency. The optimized mode MUX/DeMUX has a size of only 4 µm × 2.2 µm. An MDM-link consisting of a mode MUX and a mode DeMUX was fabricated on the silicon-on-insulator (SOI) platform. The experimental results show that the 3-dB bandwidth of the TE fundamental mode and first-order mode can reach 116 nm and 138 nm, respectively. The proposed mode MUX/DeMUX is scalable and could provide a feasible solution for constructing high-performance MDM systems.

Influence of diabetes on mortality and ICD therapies in ICD recipients: a systematic review and meta-analysis of 162,780 patients.

BACKGROUND: The influence of diabetes on the mortality and risk of implantable cardioverter defibrillator (ICD) therapies is still controversial, and a comprehensive assessment is lacking. We performed this systematic review and meta-analysis to address this controversy. METHODS: We systematically searched the PubMed, Embase, Web of Science and Cochrane Library databases to collect relevant literature. Fixed and random effects models were used to estimate the hazard ratio (HR) with 95% CIs. RESULTS: Thirty-six articles reporting on 162,780 ICD recipients were included in this analysis. Compared with nondiabetic ICD recipients, diabetic ICD recipients had higher all-cause mortality (HR = 1.45, 95% CI 1.36-1.55). The subgroup analysis showed that secondary prevention patients with diabetes may suffer a higher risk of all-cause mortality (HR = 1.89, 95% CI 1.56-2.28) (for subgroup analysis, P = 0.03). Cardiac mortality was also higher in ICD recipients with diabetes (HR = 1.68, 95% CI 1.35-2.08). However, diabetes had no significant effect on the risks of ICD therapies, including appropriate or inappropriate therapy, appropriate or inappropriate shock and appropriate anti-tachycardia pacing (ATP). Diabetes was associated with a decreased risk of inappropriate ATP (HR = 0.56, 95% CI 0.39-0.79). CONCLUSION: Diabetes is associated with an increased risk of mortality in ICD recipients, especially in the secondary prevention patients, but does not significantly influence the risks of ICD therapies, indicating that the increased mortality of ICD recipients with diabetes may not be caused by arrhythmias. The survival benefits of ICD treatment in diabetes patients are limited.

Long-term outcomes of left bundle branch area pacing versus biventricular pacing in patients with heart failure and complete left bundle branch block.

Left bundle branch area pacing (LBBAP) has developed in an effort to improve cardiac resynchronization therapy (CRT). We aimed to compare the long-term clinical outcomes between LBBAP and biventricular pacing (BIVP) in patients with heart failure (HF) and complete left bundle branch block (CLBBB). Consecutive patients with HF and CLBBB requiring CRT received either LBBAP or BIVP were recruited at the Second Affiliated Hospital of Nanchang University from February 2018 to May 2019. We assessed their implant parameters, electrocardiogram (ECG), clinical outcomes at implant and during follow-up at 1, 3, 6, 12, and 24 months. Forty-one patients recruited including 21 for LBBAP and 20 for BIVP. Mean follow-up duration was 23.71 ± 4.44 months. LBBAP produced lower pacing thresholds, shorter procedure time and fluoroscopy duration compared to BIVP. The QRS duration was significantly narrower after LBBAP than BIVP (129.29 ± 31.46 vs. 156.85 ± 26.37 ms, p = 0.005). Notably, both LBBAP and BIVP significantly improved LVEF, LVEDD, NYHA class, and BNP compared with baseline. However, LBBAP significantly lowered BNP compared with BIVP (416.69 ± 411.39 vs. 96.07 ± 788.71 pg/ml, p = 0.007) from baseline to 24-month follow-up. Moreover, patients who received LBBAP exhibited lower number of hospitalizations than those in the BIVP group (p = 0.019). In addition, we found that patients with moderately prolonged left ventricular activation time (LVAT) and QRS notching in limb leads in baseline ECG respond better to LBBAP for CLBBB correction. LBBAP might be a relative safe and effective resynchronization therapy and as a supplement to BIVP for patients with HF and CLBBB.

Successful implantation of leadless pacemaker in a patient with giant right atrium and tricuspid valve stenosis.

With the steadily increasing amount of leadless pacemaker implantations performed worldwide, it has called attention to the delivery difficulty in patients with severe large right heart. Nevertheless, limited studies have reported leadless pacemaker implantation in patients with tricuspid stenosis. Here, we report the successful implantation of leadless pacemaker in a 60-year-old female patient with giant right atrium and tricuspid valve stenosis. It is highlighted that leadless pacemaker should not be discouraged even if there are tricuspid valve stenosis and giant right atrium.

Permanent Left Bundle Branch Area Pacing for High-Degree Atrioventricular Block in a 6-Year-Old Child with 2-Year Follow-Up.

The feasibility and safety of left bundle branch area pacing (LBBAP) used in pediatric patients with atrioventricular block (AVB) have not been well demonstrated. Currently, only several case reports for pediatric patients have been published since the advent of LBBAP, with 3 months to 1 year follow-up. Here, we present a case of LBBAP in a 6-year-old child with a high-degree AVB secondary to the transcatheter device closure of congenital ventricular septal defect. No procedure-related complications were observed, and the electrical parameters were stable at 2-year follow-up. Additionally, we performed a systematic literature review on pediatric patients with LBBAP. Fifteen cases were retrieved after systematically searching PubMed and Embase databases. No complications have been reported among these published cases. In conclusion, consistent with previous cases, our case with 2-year follow-up has demonstrated that LBBAP may be an alternative pacing modality from a very early age. However, given the limited evidence, the long-term outcomes of LBBAP in pediatric patients should be further investigated.

Increased blood alpha-carotene, all-trans-Beta-carotene and lycopene levels are associated with beneficial changes in heart rate variability: a CVD-stratified analysis in an adult population-based study.

BACKGROUND: Although the associations of antioxidant micronutrients, such as carotenoids and vitamins, with cardiovascular diseases (CVDs) have been studied extensively, blood concentrations of antioxidant micronutrients and heart rate variability (HRV), which has been proven to be an indicator of cardiac autonomic control, has not been reported. We aimed to explore whether blood concentrations of antioxidant micronutrients, including carotenoids and vitamins, are associated with elevated heart rate variability (HRV (beneficial change) in a cross-sectional analysis. METHODS: Data were obtained from the Midlife in the United States (MIDUS) study that includes a general adult population. A total of 1074 (aged 34-84) individuals were included. Multivariable analyses were performed to investigate the association between main blood carotenoids (total lutein, zeaxanthin, beta-cryptoxanthin, 13-cis-beta-carotene, alpha-carotene, all-trans-beta-carotene and total lycopene) and vitamins A (retinol) and E (gamma-tocopherol and alpha-tocopherol) and HRV after adjustments were made for lifestyle factors and age-related confounders. RESULTS: Pearson correlation analyses showed that the increased levels of carotenoids and vitamins were positively correlated with higher HRV (all P < 0.05). After adjustments were made for age, gender, race, body mass index(BMI), ever-smoker, number of drinking years and exercise, blood alpha-carotene, all-trans-beta-carotene and total lycopene levels were independently associated with higher HRV in the linear regression model (all P < 0.05). Sensitivity analysis by adding "ever chronic respiratory diseases" as a covariate suggested that blood concentrations of these three carotenoids were still associated with higher low-frequency (LF)-HRV and high-frequency (HF)-HRV (all P < 0.05). Furthermore, stratified analyses suggested that the associations were affected by adding "heart disease" and "hypertension" as covariates. CONCLUSIONS: We provide the first evidence that elevated blood concentrations of alpha-carotene, trans-beta-carotene and lycopene are associated with beneficial changes in HRV in the general population. Daily intake of fruit and vegetables may be beneficial to increase blood carotenoid status and further prevent autonomic dysfunction.

Subwavelength grating based mode (de)multiplexer for 3D photonic integrated circuits.

A broadband three-dimensional (3D) mode (de) multiplexer [(De)MUX] is proposed based on the subwavelength grating (SWG) for 3D photonic integrated circuits (PICs). The proposed 3D mode (De)MUX consists of three SWG waveguides on two vertical layers. The coupling strength and operating bandwidth can be increased benefitting from both the subwavelength structure and offset between bus and access SWGs. The proposed 3D mode (De)MUX is optimized based on the 3D full-vectorial finite difference time domain method. The 1-dB bandwidths of the optimized device are over >300, 107, and 128 nm for demultiplexing TE0, TE1, and TE2 modes, respectively. The coupling lengths are only 5.0 and 1.75 µm for demultiplexing the TE1 and TE2 modes, respectively. The insertion losses are 0.12, 0.27, and 0.29 dB, respectively. The proposed 3D mode (De)MUX is also fabrication tolerant.

Low arterial oxygen partial pressure induces pulmonary thrombocytopenia in patients and a mouse model.

BACKGROUND: Recent basic studies demonstrate that the lung is a primary organ of platelet biogenesis. However, whether the pathophysiological state of the lung affect the platelets is little known. We aim to investigate the incidence of thrombocytopenia in patients with pulmonary infection (PIN) and risk factors associated with pulmonary thrombocytopenia. METHODS: In total, 11,941 patients with pulmonary infection (PIN) were enrolled, and patients with other three infectious diseases were collected as controls. The incidence of thrombocytopenia was compared, and the risk factors associated with thrombocytopenia in PIN patients were investigated by multivariate analysis. To explore the mechanism of thrombocytopenia, hypoxic model was constructed. Blood platelet counts from the angular vein (PLTs), left ventricle (PLTpost) and right ventricle (PLTpre) were determined. Megakaryocytes identified by anti-CD41 antibody were detected through flow cytometry and immunofluorescence. RESULTS: The incidence of thrombocytopenia in PIN was higher than that in other three infectious diseases (9.8% vs. 6.4% ~ 5.0%, P < 0.001). Low arterial oxygen partial pressure (PaO2) was an important risk factor for thrombocytopenia (OR = 0.88; P < 0.001). In a hypoxic mouse model, PLTs decreased (518.38 ± 127.92 vs 840.75 ± 77.30, P < 0.05), which showed that low PaO2 induced thrombocytopenia. The difference between the PLTpost and PLTpre (∆PLTpost-pre), representing the production of platelets in the lungs, was significantly attenuated in hypoxic mice when compared with normoxic mice (F = 25.47, P < 0.05). Additionally, proportions of CD41-positive megakaryocytes in the lungs, marrow, spleen all decreased in hypoxic mice. CONCLUSION: There is a high incidence for thrombocytopenia in PIN patients. Low PaO2-induced thrombocytopenia is associated with impaired generation of platelet in the lungs.

Factors Associated with a Large Decline in Renal Function or Progression to Renal Insufficiency in Hospitalized Atrial Fibrillation Patients with Early-Stage CKD.

Clinicians must consider renal function when administering anticoagulants for atrial fibrillation (AF). Determination of risk factors for renal function decline may enable identification of patients who require closer monitoring. We investigated the characteristics associated with renal function decline in patients with AF. The study cohort consisted of 631 AF patients who had at least one readmission during the follow-up period and stages 1-3 chronic kidney disease (CKD). The primary outcome measure was large renal function decline (≥30% decrease from baseline estimated glomerular filtration rate [eGFR]). The secondary outcome measure was a final eGFR < 60 mL/minute/1.73 m2 for those with a baseline eGFR above this level. The mean eGFR was 74.4 ± 18.5 mL/minute/1.73 m2, and the mean follow-up time was 30.2 ± 13.2 months. The primary outcome occurred in 155 patients (24.6%) and was associated with congestive heart failure (CHF), proteinuria, type of AF, and left atrial diameter (LAD) ≥ 45 mm. Among 478 patients with a baseline eGFR ≥ 60 mL/minute/1.73 m2, 137 (28.7%) progressed to renal failure (eGFR < 60 mL/minute/1.73 m2). A decreasing eGFR was associated with age ≥ 75 years, CHF, lower baseline eGFR, and LAD ≥ 45 mm. CHF, proteinuria, type of AF, and LAD ≥ 45 mm were associated with eGFR decline ≥ 30% in AF patients with CKD stages 1-3. Advanced age, CHF, lower baseline eGFR, and LAD ≥ 45 mm were associated with progression to renal insufficiency. These results should be considered when identifying patients who require more frequent monitoring of eGFR.

[Clinical practice guidelines for Long Q-T interval syndrome].

Long Q-T syndrome (LQTS) is an ion channel disease of the heart featuring single gene inheritance. It is characterized by prolonged QT interval, abnormal T wave, torsade de points (TdP) on electrocardiogram, with recurrent syncope, convulsion and even sudden death. Although the overall prevalence of LQTS is not high, the disease has attracted attention of cardiologists for its high incidence of sudden cardiac death. The compilation of this guideline has referred to the consensus of basic and clinical research, guidelines of other countries, and summarized the clinical manifestations, molecular basis, diagnostic criteria, treatment and prognosis, and genetic counseling of LQTS, with an aim to standardize its clinical diagnosis and treatment.

[Clinical practice guidelines for hereditary cardiomyopathy].

Cardiomyopathies are a group of heterogeneous diseases which can be caused by various factors (often genetic) and can lead to heart failure, arrhythmia and sudden death. Primary cardiomyopathies includes hereditary hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, mitochondrial cardiomyopathy, mixed (hereditary and acquired) dilated cardiomyopathy and restrictive cardiomyopathy, left ventricular densification insufficiency, and other unclassified cardiomyopathies. With the help of genomic technology, common mutations in the population have been identified. In vivo and in vitro study of such mutations has provided insight into the pathogenesis and treatment of these diseases. The compilation of this guideline is based on the consensus of basic and clinical research and guidelines from other countries, and has summarized the phenotype, diagnosis, treatment and consultation of various types of genetic cardiomyopathies with an aim to standardize the clinical management of patients.

Ankyrin-B Q1283H Variant Linked to Arrhythmias Via Loss of Local Protein Phosphatase 2A Activity Causes Ryanodine Receptor Hyperphosphorylation.

BACKGROUND: Human loss-of-function variants of ANK2 (ankyrin-B) are linked to arrhythmias and sudden cardiac death. However, their in vivo effects and specific arrhythmogenic pathways have not been fully elucidated. METHODS: We identified new ANK2 variants in 25 unrelated Han Chinese probands with ventricular tachycardia by whole-exome sequencing. The potential pathogenic variants were validated by Sanger sequencing. We performed functional and mechanistic experiments in ankyrin-B knockin (KI) mouse models and in single myocytes isolated from KI hearts. RESULTS: We detected a rare, heterozygous ANK2 variant (p.Q1283H) in a proband with recurrent ventricular tachycardia. This variant was localized to the ZU5C region of ANK2, where no variants have been previously reported. KI mice harboring the p.Q1283H variant exhibited an increased predisposition to ventricular arrhythmias after catecholaminergic stress in the absence of cardiac structural abnormalities. Functional studies illustrated an increased frequency of delayed afterdepolarizations and Ca2+ waves and sparks accompanied by decreased sarcoplasmic reticulum Ca2+ content in KI cardiomyocytes on isoproterenol stimulation. The immunoblotting results showed increased levels of phosphorylated ryanodine receptor Ser2814 in the KI hearts, which was further amplified on isoproterenol stimulation. Coimmunoprecipitation experiments demonstrated dissociation of protein phosphatase 2A from ryanodine receptor in the KI hearts, which was accompanied by a decreased binding of ankyrin-B to protein phosphatase 2A regulatory subunit B56α. Finally, the administration of metoprolol or flecainide decreased the incidence of stress-induced ventricular arrhythmias in the KI mice. CONCLUSIONS: ANK2 p.Q1283H is a disease-associated variant that confers susceptibility to stress-induced arrhythmias, which may be prevented by the administration of metoprolol or flecainide. This variant is associated with the loss of protein phosphatase 2A activity, increased phosphorylation of ryanodine receptor, exaggerated delayed afterdepolarization-mediated trigger activity, and arrhythmogenesis.

Real-World Relationship Between Proton Pump Inhibitors and Cerebro-Cardiovascular Outcomes Independent of Clopidogrel.

Previous studies have provided established evidence on adverse outcomes of the coadministration of proton pump inhibitors (PPIs) and clopidogrel, whereas cerebro-cardiovascular outcomes of PPI use in the absence of clopidogrel therapy remain controversial.In this study, we aimed to assess the association between PPIs and cerebro-cardiovascular outcomes independent of clopidogrel.Systematic searches were conducted in the Cochrane Library, PubMed, and Embase databases for all relevant studies up to August 2018. Odds ratios (ORs) with its 95% confidence intervals (CIs) were abstracted and pooled using the random-effects model.A total of 14 observational studies (13 cohort studies and 1 case-control study) were identified. Compared with non-PPI users, PPI users experienced higher risks of stroke (OR: 1.22, 95% CI: 1.08-1.36), myocardial infarction (MI; OR: 1.23, 95% CI: 1.14-1.32), cardiovascular death (OR: 1.83, 95% CI: 1.69-1.98), and major adverse cardiovascular events (MACEs; OR: 1.22, 95% CI: 1.05-1.40) independent of clopidogrel use, but not all-cause death (OR: 1.50, 95% CI: 0.99-2.25). In the subgroup analysis, PPI alone was associated with significant risks of new-onset MI (OR: 1.23, 95% CI: 1.13-1.35) and stroke (OR: 1.17, 95% CI: 1.05-1.30) in patients without previous MI or stoke and recurrent MI (OR: 1.24, 95% CI: 1.02-1.51) and stroke (OR: 1.36, 95% CI: 1.19-1.55) risks in patients with a previous MI.Based on current publications, PPI use seems to be associated with increased risks of stroke, MI, cardiovascular death, and MACEs independent of clopidogrel. Greater caution should be therefore exercised while considering its clinical benefits and further investigate any causal relationships.

FAT10 attenuates hypoxia-induced cardiomyocyte apoptosis by stabilizing caveolin-3.

FAT10, a member of the ubiquitin-like-modifier family of proteins, plays a cardioprotective role in response to hypoxic/ischemic injury. Caveolin-3 (Cav-3), a muscle-specific caveolin family member, is involved in cardiomyocyte apoptosis. However, the link between FAT10 and Cav-3 in ischemic cardiomyocytes is unclear. In the present study, we found that both FAT10 and Cav-3 were upregulated in ischemic myocardial tissues and in hypoxic cardiomyocytes. Furthermore, our results demonstrated that FAT10 inhibits hypoxia-induced cardiomyocyte apoptosis by increasing Cav-3 expression. Importantly, following myocardial infarction, knockout of FAT10 aggravated cardiac dysfunction and increased cardiomyocyte apoptosis by reducing Cav-3 expression. Additionally, Cav-3 was degraded by the ubiquitin-proteasome system (UPS) in cardiomyocytes. Mechanistically, we found that FAT10 stabilizes Cav-3 expression by inhibiting ubiquitination-mediated degradation in cardiomyocytes. Together, these findings revealed a novel role of FAT10 in protection against ischemia-induced injury via stabilization of Cav-3, providing evidence that the FAT10/Cav-3 axis may be a potential therapeutic target for patients with ischemic heart conditions.

A rare form of extremely wide QRS complex due to reversed homologous electrical ventricular separation of acute heart failure.

Electrical ventricular separation, as a special complete intraventricular block, denotes that ventricles be electrically separated into two or more parts caused by severe and wide damage of myocardium and conduction. Electrical ventricular separation can be divided into homologous and heterologous, homologous electrical ventricular separation is a rare phenomenon, literally the excitement of whole ventricle originate from supraventricle, on ECG, there are two different QRS waves which connect with an isoelectric line, one ST segment and T wave. We report a valve heart disease presented with complicated electrophysiological characteristics, which has reversed complex homologous electrical ventricular separation with second degree intraventricular block.

Errata: Do Implantable Cardioverter Defibrillators Reduce Mortality in Patients With Chronic Kidney Disease at All Stages? An Updated Meta-Analysis.

The errors in the following list appeared in the article titled "Do Implantable Cardioverter Defibrillators Reduce Mortality in Patients With Chronic Kidney Disease at All Stages?: An Updated Meta-Analysis" by Linghua Fu, Qiongqiong Zhou, Wengen Zhu, Lin Huang, Ying Ding, Yang Shen, Jinzhu Hu, and Kui Hong (Vol. 58, No. 3, 371-7, 2017).

Do Implantable Cardioverter Defibrillators Reduce Mortality in Patients With Chronic Kidney Disease at All Stages?

The benefits of implantable cardioverter defibrillator (ICD) implantation in chronic kidney disease (CKD) patients with high sudden cardiac death (SCD) risk are uncertain. To clarify the effects of receiving an ICD in CKD patients, we conducted this meta-analysis to identify the effects of ICDs on patients with CKD, including those on dialysis. We searched the Cochrane library, EMBASE, PubMed, and clinical trials for studies published before July 2016. Eleven studies including 20,196 CKD patients were considered for inclusion. The pooled analysis suggested that patients with an estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73 m2 would benefit from receiving treatments with ICDs compared with patients without an ICD device (aHR = 0.74; 95% confidence interval [CI], 0.63 to 0.86). [corrected]. This is the first report of a subgroup analysis on the survival rate of ICD implantation in CKD patients according to an eGFR group. The subgroup analysis indicated a similar protective association of ICDs in stage 3 (aHR = 0.71; 95% CI, 0.61 to 0.82) and 5 (aHR = 0.71; 95% CI, 0.54 to 0.92) CKD patients [corrected] compared with the control group. However, there was no significant improvement in all-cause mortality in stage 4 CKD patients (aHR = 1.02; 95%CI, 0.75 to 1.37) [corrected]. This is the first meta-analysis reporting that ICD implantation reduces all-cause mortality in stage 3 and 5 [corrected] CKD patients. However, the data do not indicate there is any benefit to ICD implantation in stage 4 [corrected] CKD patients.

Warfarin use and the risks of stroke and bleeding in hemodialysis patients with atrial fibrillation: A systematic review and a meta-analysis.

BACKGROUND AND AIM: The efficacy and safety of warfarin therapy in hemodialysis (HD) patients with atrial fibrillation (AF) remains controversial. Thus, we performed, up to date, the first meta-analysis on the risks of stroke and bleeding in warfarin treatment in these populations. METHODS AND RESULTS: The relevant literature was searched using the following electronic databases without any language restrictions: the Cochrane Library Database, PubMed, ISI, Ovid, and Chinese Biomedical Database from the establishment of the database to October 2014. The studies were included if (a) studies described the risk of stroke or bleeding with or without warfarin in dialysis patients with AF, (b) studies provided information about hazard ratio (HR) and 95% confidence interval (CI) of stroke or bleeding, and (c) the study design was a clinical cohort. The inverse variance method was used to obtain overall HRs and 95% CIs. Sensitivity analyses and publication bias were also performed. We identified six eligible studies with a total of 9816 patients. Combined HRs showed that warfarin cannot prevent strokes in HD patients with AF (HR = 1.23, 95% CI 0.80-1.87; P = 0.347), but its use was associated with a higher risk of bleeding (HR = 1.20, 95% CI 1.03-1.39; P = 0.019). CONCLUSION: This meta-analysis suggested that warfarin should not be recommended for the routine treatment of HD patients with AF.

[High incidence of sudden cardiac death in one family with type-3 long QT syndrome: molecular genetics and electrophysiology mechanism analysis].

OBJECTIVES: We identified the long QT syndrome (LQTS) patients, and detected the potential risk of LQTS in family members by using genetic testing and electrophysiological analysis, which helped provide clinical evaluation and appropriate treatment. METHODS: Detailed clinical characteristics and familiar history were obtained from the whole family members of an idiopathic pediatric LQTS patient. Two hundred healthy subjects with the same ethnic background were recruited as controls. The entire coding sequences of three candidate genes including KCNQ1, KCNH2 and SCN5A were screened for mutations in the proband. The function of the mutation was then explored by whole-cell patch clamp techniques, and the genetic testing and risk assessment of the family members were performed. RESULTS: The proband was clinically preliminary diagnosed as LQTS by 12-lead electrocardiogram. On the third day of metoprolol intake (25 mg, bid), she died suddenly at lunch. One heterozygous missense mutation (SCN5A-V411M) was identified in this proband, but the mutation was absent in 200 healthy subjects. The electrophysiological analysis indicated that SCN5A-V411M significantly increased the peak current density ((230.8 ± 27.6)pA/pF vs. (101.2 ± 10.9)pA/pF, n=10, P<0.01) and the late sodium current ((156.6 ± 13.6)pA/pF vs. (95.9 ± 7.9)pA/pF, n=12, P<0.01) of sodium channel compared to wide type. The enhanced sodium channel activation with a negative shift in the peak I-V relationship was significantly higher by -50 mV than wide type (85.0%± 7.4% vs. 41.5% ± 2.6%, P<0.01), while the steady-state inactivation curves remained unchanged. Additionally, mother and grandmother of the proband were the silent mutation carriers with no symptoms, who needed the appropriate clinical assessment and follow-up. The proband's twin sister and aunt died of sudden infant death syndrome. CONCLUSIONS: We firstly reported a heterozygote missense mutation (SCN5A-V411M) in this Chinese family. V411M induced "gain of function" of sodium channel and formed the basis of type-3 LQTS. Genetic testing could help to increase the diagnostic accuracy, and facilitate clinical assessment and appropriate therapy to prevent sudden cardiac death of individuals with SCN5A-V411M mutation.

A novel contact force sensing pulsed field ablation catheter in a porcine model.

BACKGROUND: Pulsed field ablation (PFA) has emerged as a novel non-thermal modality with highly myocardium-specific. However, the PFA catheter based on contact force (CF)-sensing has not been reported. The study aimed to evaluate the efficacy and safety of a novel CF-sensing PFA catheter. METHODS: First, different CF (5, 15, 25, and 35 g) of the novel PFA catheter were evaluated on lesion dimensions during ablation on right and left ventricle in two pigs. Next, this catheter was further evaluated on four typical sites of superior vena cava (SVC), cavotricuspid isthmus (CTI), right superior pulmonary vein (RSPV), and right inferior pulmonary vein (RIPV) for atrial ablation in another six pigs. Electrical isolation was evaluated immediately after ablation and 30-day survival. Chronic lesions were assessed via histopathology after euthanasia. Acute and chronic safety outcomes were observed peri- and post-procedurally. RESULTS: In ventricular ablation, increased CF from 5 to 15 g produced significantly greater lesion depth but nonsignificant increases from 15 to 35 g. In atrial ablation, the novel CF-sensing PFA deliveries produced an acute attenuation of local electrograms and formation of a continuous line of block in all 6 pigs. The ablation line remained sustained blockage at the 30-day survival period. The CF of SVC, CTI, RSPV, and RIPV was 9.4 ± 1.5, 14.5 ± 3.2, 17.2 ± 2.6, and 13.4 ± 2.8 g, respectively. Moreover, no evidence of damage to esophagus or phrenic nerve was observed. CONCLUSION: The novel CF-sensing PFA catheter potentiated efficient, safe, and durable ablation, without causing damage to the esophagus or phrenic nerve.