Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital hea...Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital heart disease(ACHD)patients undergoing electrophysiological(EP)procedures.We sought to evaluate the safety and efficacy of ultrasound-guided puncture and postprocedural Z-stitch hemostasis for ACHD patients under-going EP procedures.Methods and Results:The population of ACHD patients undergoing transfemoral EP pro-cedures at the University of Zurich Heart Center between January 2019 and December 2022 was observed and analyzed.During the study period,femoral access(left/right,arterial/venous)was performed under real-time ultrasound guidance.At the end of the procedure,a single Z-stitch was performed at the puncture site.We eval-uated the incidence of in-hospital complications associated with femoral access puncture in this population.Among 101 patients who had a total of 147 previous ipsilateral vascular punctures(mean 1.5 per person),100 patients underwent successful femoral vascular access for EP procedures.The median age of the patients was 47±15 years and 34(34%)were male.Z-stitches were performed after the procedure in 100 patients with 303 femoral vascular accesses(mean 3 punctures per person).No patient developed vascular puncture relevant inguinal hematoma,pseudo aneurysm,arteriovenousfistula,venous or arterial thrombosis.Conclusion:In ACHD patients undergoing EP procedures,optimal femoral access management can be achieved with ultra-sound-guided puncture and postprocedural Z-stitch hemostasis.展开更多
Arrhythmogenic ventricular cardiomyopathy(AVC) isgenerally referred to as arrhythmogenic right ventricu-lar(RV) cardiomyopathy/dysplasia and constitutesan inherited cardiomyopathy.Affected patients maysuccumb to sudde...Arrhythmogenic ventricular cardiomyopathy(AVC) isgenerally referred to as arrhythmogenic right ventricu-lar(RV) cardiomyopathy/dysplasia and constitutesan inherited cardiomyopathy.Affected patients maysuccumb to sudden cardiac death(SCD),ventriculartachyarrhythmias(VTA) and heart failure.Geneticstudies have identified causative mutations in genesencoding proteins of the intercalated disk that lead toreduced myocardial electro-mechanical stability.Theterm arrhythmogenic RV cardiomyopathy is somewhatmisleading as biventricular involvement or isolated leftventricular(LV) involvement may be present and thus abroader term such as AVC should be preferred.The di-agnosis is established on a point score basis accordingto the revised 2010 task force criteria utilizing imagingmodalities,demonstrating fibrous replacement throughbiopsy,electrocardiographic abnormalities,ventricu-lar arrhythmias and a positive family history includingidentification of genetic mutations.Although severarisk factors for SCD such as previous cardiac arrest,syncope,documented VTA,severe RV/LV dysfunctionand young age at manifestation have been identified,risk stratification still needs improvement,especially inasymptomatic family members.Particularly,the roleof genetic testing and environmental factors has to befurther elucidated.Therapeutic interventions include re-striction from physical exercise,beta-blockers,sotalol,amiodarone,implantable cardioverter-defibrillators andcatheter ablation.Life-long follow-up is warranted insymptomatic patients,but also asymptomatic carriersof pathogenic mutations.展开更多
Much effort has been made to uncover the cellular heterogeneities of human hearts by single-nucleus RNA sequencing.However,the cardiac transcriptional regulation networks have not been systematically described because...Much effort has been made to uncover the cellular heterogeneities of human hearts by single-nucleus RNA sequencing.However,the cardiac transcriptional regulation networks have not been systematically described because of the limitations in detecting transcription factors.In this study,we optimized a pipeline for isolating nuclei and conducting single-nucleus RNA sequencing targeted to detect a higher number of cell signal genes and an optimal number of transcription factors.With this unbiased protocol,we characterized the cellular composition of healthy human hearts and investigated the transcriptional regulation networks involved in determining the cellular identities and functions of the main cardiac cell subtypes.Particularly in fibroblasts,a novel regulator,PKNOX2,was identified as being associated with physiological fibroblast activation in healthy hearts.To validate the roles of these transcription factors in maintaining homeostasis,we used single-nucleus RNA-sequencing analysis of transplanted failing hearts focusing on fibroblast remodelling.The trajectory analysis suggested that PKNOX2 was abnormally decreased from fibroblast activation to pathological myofibroblast formation.Both gain-and loss-of-function in vitro experiments demonstrated the inhibitory role of PKNOX2 in pathological fibrosis remodelling.Moreover,fibroblast-specific overexpression and knockout of PKNOX2 in a heart failure mouse model induced by transverse aortic constriction surgery significantly improved and aggravated myocardial fibrosis,respectively.In summary,this study established a high-quality pipeline for single-nucleus RNA-sequencing analysis of heart muscle.With this optimized protocol,we described the transcriptional regulation networks of the main cardiac cell subtypes and identified PKNOX2 as a novel regulator in suppressing fibrosis and a potential therapeutic target for future translational studies.展开更多
基金This study complied with the Declaration of Helsinki and was approved by the local Ethics Committee(Cantonal Ethics Committee Zurich,Nr.2016-00116).All patients signed informed consent for the procedure and the use of clinical data for scientific study.
文摘Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital heart disease(ACHD)patients undergoing electrophysiological(EP)procedures.We sought to evaluate the safety and efficacy of ultrasound-guided puncture and postprocedural Z-stitch hemostasis for ACHD patients under-going EP procedures.Methods and Results:The population of ACHD patients undergoing transfemoral EP pro-cedures at the University of Zurich Heart Center between January 2019 and December 2022 was observed and analyzed.During the study period,femoral access(left/right,arterial/venous)was performed under real-time ultrasound guidance.At the end of the procedure,a single Z-stitch was performed at the puncture site.We eval-uated the incidence of in-hospital complications associated with femoral access puncture in this population.Among 101 patients who had a total of 147 previous ipsilateral vascular punctures(mean 1.5 per person),100 patients underwent successful femoral vascular access for EP procedures.The median age of the patients was 47±15 years and 34(34%)were male.Z-stitches were performed after the procedure in 100 patients with 303 femoral vascular accesses(mean 3 punctures per person).No patient developed vascular puncture relevant inguinal hematoma,pseudo aneurysm,arteriovenousfistula,venous or arterial thrombosis.Conclusion:In ACHD patients undergoing EP procedures,optimal femoral access management can be achieved with ultra-sound-guided puncture and postprocedural Z-stitch hemostasis.
基金Supported by The Georg and Bertha Schwyzer-Winiker Foundation,Zurich,Switzerland
文摘Arrhythmogenic ventricular cardiomyopathy(AVC) isgenerally referred to as arrhythmogenic right ventricu-lar(RV) cardiomyopathy/dysplasia and constitutesan inherited cardiomyopathy.Affected patients maysuccumb to sudden cardiac death(SCD),ventriculartachyarrhythmias(VTA) and heart failure.Geneticstudies have identified causative mutations in genesencoding proteins of the intercalated disk that lead toreduced myocardial electro-mechanical stability.Theterm arrhythmogenic RV cardiomyopathy is somewhatmisleading as biventricular involvement or isolated leftventricular(LV) involvement may be present and thus abroader term such as AVC should be preferred.The di-agnosis is established on a point score basis accordingto the revised 2010 task force criteria utilizing imagingmodalities,demonstrating fibrous replacement throughbiopsy,electrocardiographic abnormalities,ventricu-lar arrhythmias and a positive family history includingidentification of genetic mutations.Although severarisk factors for SCD such as previous cardiac arrest,syncope,documented VTA,severe RV/LV dysfunctionand young age at manifestation have been identified,risk stratification still needs improvement,especially inasymptomatic family members.Particularly,the roleof genetic testing and environmental factors has to befurther elucidated.Therapeutic interventions include re-striction from physical exercise,beta-blockers,sotalol,amiodarone,implantable cardioverter-defibrillators andcatheter ablation.Life-long follow-up is warranted insymptomatic patients,but also asymptomatic carriersof pathogenic mutations.
基金The authors thank Prof.Xuegong Zhang from Tsinghua University for his assistance and suggestion on the data process.This work is supported by the National Natural Science Foundation of China(82100377)National High Level Hospital Clinical Research Funding(2023-GSP-RC-01,2023-GSP-ZD-2)the Beijing Nova Program(Z211100002121046,20220484205).Figure 10 was created with BioRender.com.
文摘Much effort has been made to uncover the cellular heterogeneities of human hearts by single-nucleus RNA sequencing.However,the cardiac transcriptional regulation networks have not been systematically described because of the limitations in detecting transcription factors.In this study,we optimized a pipeline for isolating nuclei and conducting single-nucleus RNA sequencing targeted to detect a higher number of cell signal genes and an optimal number of transcription factors.With this unbiased protocol,we characterized the cellular composition of healthy human hearts and investigated the transcriptional regulation networks involved in determining the cellular identities and functions of the main cardiac cell subtypes.Particularly in fibroblasts,a novel regulator,PKNOX2,was identified as being associated with physiological fibroblast activation in healthy hearts.To validate the roles of these transcription factors in maintaining homeostasis,we used single-nucleus RNA-sequencing analysis of transplanted failing hearts focusing on fibroblast remodelling.The trajectory analysis suggested that PKNOX2 was abnormally decreased from fibroblast activation to pathological myofibroblast formation.Both gain-and loss-of-function in vitro experiments demonstrated the inhibitory role of PKNOX2 in pathological fibrosis remodelling.Moreover,fibroblast-specific overexpression and knockout of PKNOX2 in a heart failure mouse model induced by transverse aortic constriction surgery significantly improved and aggravated myocardial fibrosis,respectively.In summary,this study established a high-quality pipeline for single-nucleus RNA-sequencing analysis of heart muscle.With this optimized protocol,we described the transcriptional regulation networks of the main cardiac cell subtypes and identified PKNOX2 as a novel regulator in suppressing fibrosis and a potential therapeutic target for future translational studies.