Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms an...Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.展开更多
Cardiomyopathy is a pathological condition characterized by cardiac pump failure due to myocardial dysfunction and the major cause of advanced heart failure requiring heart transplantation.Although optimized medical t...Cardiomyopathy is a pathological condition characterized by cardiac pump failure due to myocardial dysfunction and the major cause of advanced heart failure requiring heart transplantation.Although optimized medical therapies have been developed for heart failure during the last few decades,some patients with cardiomyopathy exhibit advanced heart failure and are refractory to medical therapies.Desmosome,which is a dynamic cell-to-cell junctional component,maintains the structural integrity of heart tissues.Genetic mutations in desmo-somal genes cause arrhythmogenic cardiomyopathy(AC),a rare inheritable disease,and predispose patients to sudden cardiac death and heart failure.Recent advances in sequencing technologies have elucidated the genetic basis of cardiomyopathies and revealed that desmosome-related cardiomyopathy is concealed in broad cardiomyopathies.Among desmosomal genes,mutations in PKP2(which encodes PKP2)are most frequently identified in patients with AC.PKP2 deficiency causes various pathological cardiac phenotypes.Human cardiomyocytes differentiated from patient-derived induced pluripotent stem cells(iPSCs)in combination with genome editing,which allows the precise arrangement of the targeted genome,are powerful experimental tools for studying disease.This review summarizes the current issues associated with practical medicine for advanced heart failure and the recent advances in disease modeling using iPSC-derived cardiomyocytes targeting desmosome-related cardiomyopathy caused by PKP2 deficiency.展开更多
Purpose: The role of GPER in sepsis-induced myocardial cell injury and its potential impact on the risk of death within 28 days in sepsis. Methods: An in vitro experiment was conducted to establish a sepsis-induced my...Purpose: The role of GPER in sepsis-induced myocardial cell injury and its potential impact on the risk of death within 28 days in sepsis. Methods: An in vitro experiment was conducted to establish a sepsis-induced myocardial cell model. H9C2 myocardial cells were treated with 10 μg/ml lipopolysaccharide (LPS) for 24 hours. The effects of different concentrations of the GPER agonist G1 (1, 3, and 10 μmol/L) on cell viability, expression of inflammatory markers, cell apoptosis, and the NF-κB pathway were evaluated. A Mendelian randomization analysis was conducted using Single Nucleotide Polymorphism (SNPs) related to the GPER gene as instrumental variables to investigate the causal relationship between the GPER gene variations and sepsis (28-day death). Results: The results indicate that the group treated with LPS showed a significant decrease in myocardial cell viability, an increase in concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), higher apoptosis rates, and increased phosphorylation levels of NF-κB p65 (p-P65/P65) and IκB-α (p-IκB-α/IκB-α) compared to the control group (P κB pathway. However, genetic evidence did not show a causal relationship between GPER gene variations and sepsis (28-day death) (P κB pathway. However, genetic evidence did not show a causal relationship between GPER gene variations and sepsis (28-day death).展开更多
Among inherited cardiac conditions,a special place is kept by cardiomyopathies(CMPs)and channelopathies(CNPs),which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause ea...Among inherited cardiac conditions,a special place is kept by cardiomyopathies(CMPs)and channelopathies(CNPs),which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause early mortality.Like other inherited cardiac conditions,genetic CMPs and CNPs exhibit incomplete penetrance and variable expressivity even within carriers of the same pathogenic deoxyribonucleic acid variant,challenging our understanding of the underlying pathogenic mechanisms.Until recently,the lack of accurate physiological preclinical models hindered the investigation of fundamental cellular and molecular mechanisms.The advent of induced pluripotent stem cell(iPSC)technology,along with advances in gene editing,offered unprecedented opportunities to explore hereditary CMPs and CNPs.Hallmark features of iPSCs include the ability to differentiate into unlimited numbers of cells from any of the three germ layers,genetic identity with the subject from whom they were derived,and ease of gene editing,all of which were used to generate“disease-in-a-dish”models of monogenic cardiac conditions.Functionally,iPSC-derived cardiomyocytes that faithfully recapitulate the patient-specific phenotype,allowed the study of disease mechanisms in an individual-/allele-specific manner,as well as the customization of therapeutic regimen.This review provides a synopsis of the most important iPSC-based models of CMPs and CNPs and the potential use for modeling disease mechanisms,personalized therapy and deoxyribonucleic acid variant functional annotation.展开更多
Background: Chronic excessive alcohol consumption has been strongly associated with alcohol-induced cardiomyopathy (AC) in patients with no evidence of coronary artery disease (CAD). AC may cause cardiovascular c...Background: Chronic excessive alcohol consumption has been strongly associated with alcohol-induced cardiomyopathy (AC) in patients with no evidence of coronary artery disease (CAD). AC may cause cardiovascular complications and significant impact on the quality of life. We discuss an interesting case of dilated cardiomyopathy, associated complication, diagnostic work-up and management. Case Report: A young male presented to our service with worsening dyspnea, orthopnea, and scrotal and lower extremity edema. On average, he consumed a pack of 12 beers every day and had a 30-pack-years smoking history. He was found to be in acute heart failure with evidence of pulmonary edema and cardiomegaly on chest imaging. He had biventricular dilatation and severely reduced left ventricular ejection fraction (LVEF) 15% in addition to a thrombus in the LV apex. The cardiac catheterization was unremarkable for CAD. He was diuresed appropriately resulting in significant weight loss and resolution of symptoms. LV thrombus was treated with unfractionated heparin infusion that was transitioned to warfarin. He was maintained on guidelines-directed medical therapy for heart failure. Extensive counseling was provided regarding alcohol and tobacco cessation. On follow-up echocardiogram, his LVEF improved and there was no evidence of LV thrombus. We think, the readership will benefit from our experience of treating a case of AC, and the importance of clinical history. Conclusion: Chronic excessive alcohol use is detrimental to cardiac function leading to alcohol-induced cardiomyopathy. A careful approach to clinical history of alcohol consumption and prompt diagnostic workup negative for ischemic causes may confirm the diagnosis. Cardiac function improves with guidelines-directed medical therapy for heart failure and abstinence from alcohol.展开更多
Purpose: To investigate the alteration of left ventricular function in subjects with persistent atrial tachyarrhythmia induced cardiomyopathy (TIC) undergoing radiofrequency ablation, and to study the pathogenesis and...Purpose: To investigate the alteration of left ventricular function in subjects with persistent atrial tachyarrhythmia induced cardiomyopathy (TIC) undergoing radiofrequency ablation, and to study the pathogenesis and effective treatment of TIC. Methods: A total of 25 cases with persistent atrial tachyarrhythmia and impaired left ventricular systolic function were studied (16 men and 9 women, aged 53.3 ± 15.2 years), and all subjects underwent electrophysiological study and radiofrequency ablation of atrial tachyarrhythmia under the guidance of CARTO system during 2006.9-2011.8. Indexes related to cardiac function, including left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), New York Heart Association functional classification (NYHA class), 6 minutes walking test (6MWT), N-terminal pro-brain natriuretic peptide (BNP) and 24 hours average heart rate (AHR), were analyzed at the time point of 7 days, 3 and 6 months after the procedure as well as 1 day before ablation. Results: No refractory atrial arrhythmia recurred in all cases after ablation, compared with LVEDD (51.7 ± 4.5 mm), LVEF (39.0% ± 4.3%), number of patients with NYHA class IV and III (n = 17), 6MWT (212 ± 56 m), BNP (3622 ± 1860 ng/L) and AHR (112.5 ± 23.2 bpm) before ablation, the index of LVEDD (45.2 ± 3.3 mm;41.7 ± 2.5 mm;40.5 ± 3.1 m), BNP (2429 ± 1355 ng/L;1530 ± 866 ng/L;1300 ± 520 ng/L), total number of patients of NYHA class IV and III (n = 11;3;2) and AHR (73.3 ± 15.3 bpm;68.7 ± 13.5 bpm;66.3 ± 13.6 bpm) significantly decreased (P < 0.05), LVEF (45.6 ± 3.5%;51.5 ± 2.7%;53.5 ± 3.1%) and 6MWT (262 ± 47 m;305 ± 37 m;313 ± 41 m) greatly increased (P < 0.05)in 7 days, 3 and 6 months after ablation respectively. There was a statistical difference between 7 days and 3 or 6 months after ablation in above-mentioned indexes (P < 0.05) except AHR (P > 0.05), no significant difference existed between 3 and 6 months in all indexes (P > 0.05). Conclusion: long-lasting atrial arrhythmia with rapid ventricular response could impair left ventricle function, which could be reversed within weeks after successful ablation and restoration of sinus rhythm.展开更多
Causative mutations and variants associated with cardiac diseases have been found in genes encoding cardiac ion channels, accessory proteins, cytoskeletal components, junctional proteins, and signaling molecules. In m...Causative mutations and variants associated with cardiac diseases have been found in genes encoding cardiac ion channels, accessory proteins, cytoskeletal components, junctional proteins, and signaling molecules. In most cases the functional evaluation of the genetic alterationhas been carried out by expressing the mutated proteins in in-vitro heterologous systems. While these studies have provided a wealth of functional details that have greatly enhanced the understanding of the pathological mechanisms, it has always been clear that heterologous expression of the mutant protein bears the intrinsic limitation of the lack of a proper intracellular environment and the lack of pathological remodeling. The results obtained from the application of the next generation sequencing technique to patients suffering from cardiac diseases have identified several loci, mostly in non-coding DNA regions, which still await functional analysis. The isolation and culture of human embryonic stem cells has initially provided a constant source of cells from which cardiomyocytes(CMs) can be obtained by differentiation. Furthermore, the possibility to reprogram cellular fate to a pluripotent state, has opened this process to the study of genetic diseases. Thus induced pluripotent stem cells(i PSCs) represent a completely new cellular model that overcomes the limitations of heterologous studies. Importantly, due to the possibility to keep spontaneously beating CMs in culture for several months, during which they show a certain degree of maturation/aging, this approach will also provide a system in which to address the effect of long-term expression of the mutated proteins or any other DNA mutation, in terms of electrophysiological remodeling. Moreover, since i PSC preserve the entire patients' genetic context, the system will help the physicians in identifying the most appropriate pharmacological intervention to correct the functional alteration. This article summarizes the current knowledge of cardiac genetic diseases modelled with i PSC.展开更多
目的:基于CiteSpace知识图谱探讨近10年脓毒症心肌病(SICM)的研究现状和研究热点。方法:通过Web of Science检索2012—2022年6月SICM相关文献,应用文献计量学研究方法和CiteSpace软件对SICM文献的产出数量、国家/地区、研究机构、发文...目的:基于CiteSpace知识图谱探讨近10年脓毒症心肌病(SICM)的研究现状和研究热点。方法:通过Web of Science检索2012—2022年6月SICM相关文献,应用文献计量学研究方法和CiteSpace软件对SICM文献的产出数量、国家/地区、研究机构、发文作者和共被引作者及双图叠加共被引期刊网络、关键词时间线网络和共被引文献网络进行文献计量学分析和可视化展示,探讨SICM研究现状和研究热点。结果:共纳入3814篇文献,近10年SICM相关文献逐年增长,2016年开始文献产出激增。从国家/地区、研究机构和作者发文频次角度,中国与欧美国家齐头并进,但是从论文影响力和共被引作者角度看,我国与欧美国家仍差距明显。近2年和近10年期刊共被引频次排名前10位的杂志相同,包括Crit Care Med、Crit Care等。SICM研究热点包括急性肾损伤、脓毒症心肌损伤、脓毒症休克、心源性休克、心肌梗死,涉及SICM的病因、病理机制、评估、治疗、并发症和预后。频次排名前10位的高被引文献主要为脓毒症的指南共识和随机对照试验及SICM研究综述。结论:基于CiteSpace对SICM文献进行计量学分析,可以更加清晰、直观地了解到全球SICM的研究现状,有助于总结该领域的研究现状,推动该领域的发展。展开更多
文摘Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.
基金Supported by JSPS KAKENHI,No.20K21602,No.21H02915,and No.22K19526the Japan Agency for Medical Research and Development,No.21bm0804008h0005+2 种基金the Cell Science Research Foundationthe Grant for Basic Research of the Japanese Circulation Society(2018)SENSHIN Medical Research Foundation.
文摘Cardiomyopathy is a pathological condition characterized by cardiac pump failure due to myocardial dysfunction and the major cause of advanced heart failure requiring heart transplantation.Although optimized medical therapies have been developed for heart failure during the last few decades,some patients with cardiomyopathy exhibit advanced heart failure and are refractory to medical therapies.Desmosome,which is a dynamic cell-to-cell junctional component,maintains the structural integrity of heart tissues.Genetic mutations in desmo-somal genes cause arrhythmogenic cardiomyopathy(AC),a rare inheritable disease,and predispose patients to sudden cardiac death and heart failure.Recent advances in sequencing technologies have elucidated the genetic basis of cardiomyopathies and revealed that desmosome-related cardiomyopathy is concealed in broad cardiomyopathies.Among desmosomal genes,mutations in PKP2(which encodes PKP2)are most frequently identified in patients with AC.PKP2 deficiency causes various pathological cardiac phenotypes.Human cardiomyocytes differentiated from patient-derived induced pluripotent stem cells(iPSCs)in combination with genome editing,which allows the precise arrangement of the targeted genome,are powerful experimental tools for studying disease.This review summarizes the current issues associated with practical medicine for advanced heart failure and the recent advances in disease modeling using iPSC-derived cardiomyocytes targeting desmosome-related cardiomyopathy caused by PKP2 deficiency.
文摘Purpose: The role of GPER in sepsis-induced myocardial cell injury and its potential impact on the risk of death within 28 days in sepsis. Methods: An in vitro experiment was conducted to establish a sepsis-induced myocardial cell model. H9C2 myocardial cells were treated with 10 μg/ml lipopolysaccharide (LPS) for 24 hours. The effects of different concentrations of the GPER agonist G1 (1, 3, and 10 μmol/L) on cell viability, expression of inflammatory markers, cell apoptosis, and the NF-κB pathway were evaluated. A Mendelian randomization analysis was conducted using Single Nucleotide Polymorphism (SNPs) related to the GPER gene as instrumental variables to investigate the causal relationship between the GPER gene variations and sepsis (28-day death). Results: The results indicate that the group treated with LPS showed a significant decrease in myocardial cell viability, an increase in concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), higher apoptosis rates, and increased phosphorylation levels of NF-κB p65 (p-P65/P65) and IκB-α (p-IκB-α/IκB-α) compared to the control group (P κB pathway. However, genetic evidence did not show a causal relationship between GPER gene variations and sepsis (28-day death) (P κB pathway. However, genetic evidence did not show a causal relationship between GPER gene variations and sepsis (28-day death).
文摘Among inherited cardiac conditions,a special place is kept by cardiomyopathies(CMPs)and channelopathies(CNPs),which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause early mortality.Like other inherited cardiac conditions,genetic CMPs and CNPs exhibit incomplete penetrance and variable expressivity even within carriers of the same pathogenic deoxyribonucleic acid variant,challenging our understanding of the underlying pathogenic mechanisms.Until recently,the lack of accurate physiological preclinical models hindered the investigation of fundamental cellular and molecular mechanisms.The advent of induced pluripotent stem cell(iPSC)technology,along with advances in gene editing,offered unprecedented opportunities to explore hereditary CMPs and CNPs.Hallmark features of iPSCs include the ability to differentiate into unlimited numbers of cells from any of the three germ layers,genetic identity with the subject from whom they were derived,and ease of gene editing,all of which were used to generate“disease-in-a-dish”models of monogenic cardiac conditions.Functionally,iPSC-derived cardiomyocytes that faithfully recapitulate the patient-specific phenotype,allowed the study of disease mechanisms in an individual-/allele-specific manner,as well as the customization of therapeutic regimen.This review provides a synopsis of the most important iPSC-based models of CMPs and CNPs and the potential use for modeling disease mechanisms,personalized therapy and deoxyribonucleic acid variant functional annotation.
文摘Background: Chronic excessive alcohol consumption has been strongly associated with alcohol-induced cardiomyopathy (AC) in patients with no evidence of coronary artery disease (CAD). AC may cause cardiovascular complications and significant impact on the quality of life. We discuss an interesting case of dilated cardiomyopathy, associated complication, diagnostic work-up and management. Case Report: A young male presented to our service with worsening dyspnea, orthopnea, and scrotal and lower extremity edema. On average, he consumed a pack of 12 beers every day and had a 30-pack-years smoking history. He was found to be in acute heart failure with evidence of pulmonary edema and cardiomegaly on chest imaging. He had biventricular dilatation and severely reduced left ventricular ejection fraction (LVEF) 15% in addition to a thrombus in the LV apex. The cardiac catheterization was unremarkable for CAD. He was diuresed appropriately resulting in significant weight loss and resolution of symptoms. LV thrombus was treated with unfractionated heparin infusion that was transitioned to warfarin. He was maintained on guidelines-directed medical therapy for heart failure. Extensive counseling was provided regarding alcohol and tobacco cessation. On follow-up echocardiogram, his LVEF improved and there was no evidence of LV thrombus. We think, the readership will benefit from our experience of treating a case of AC, and the importance of clinical history. Conclusion: Chronic excessive alcohol use is detrimental to cardiac function leading to alcohol-induced cardiomyopathy. A careful approach to clinical history of alcohol consumption and prompt diagnostic workup negative for ischemic causes may confirm the diagnosis. Cardiac function improves with guidelines-directed medical therapy for heart failure and abstinence from alcohol.
文摘Purpose: To investigate the alteration of left ventricular function in subjects with persistent atrial tachyarrhythmia induced cardiomyopathy (TIC) undergoing radiofrequency ablation, and to study the pathogenesis and effective treatment of TIC. Methods: A total of 25 cases with persistent atrial tachyarrhythmia and impaired left ventricular systolic function were studied (16 men and 9 women, aged 53.3 ± 15.2 years), and all subjects underwent electrophysiological study and radiofrequency ablation of atrial tachyarrhythmia under the guidance of CARTO system during 2006.9-2011.8. Indexes related to cardiac function, including left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), New York Heart Association functional classification (NYHA class), 6 minutes walking test (6MWT), N-terminal pro-brain natriuretic peptide (BNP) and 24 hours average heart rate (AHR), were analyzed at the time point of 7 days, 3 and 6 months after the procedure as well as 1 day before ablation. Results: No refractory atrial arrhythmia recurred in all cases after ablation, compared with LVEDD (51.7 ± 4.5 mm), LVEF (39.0% ± 4.3%), number of patients with NYHA class IV and III (n = 17), 6MWT (212 ± 56 m), BNP (3622 ± 1860 ng/L) and AHR (112.5 ± 23.2 bpm) before ablation, the index of LVEDD (45.2 ± 3.3 mm;41.7 ± 2.5 mm;40.5 ± 3.1 m), BNP (2429 ± 1355 ng/L;1530 ± 866 ng/L;1300 ± 520 ng/L), total number of patients of NYHA class IV and III (n = 11;3;2) and AHR (73.3 ± 15.3 bpm;68.7 ± 13.5 bpm;66.3 ± 13.6 bpm) significantly decreased (P < 0.05), LVEF (45.6 ± 3.5%;51.5 ± 2.7%;53.5 ± 3.1%) and 6MWT (262 ± 47 m;305 ± 37 m;313 ± 41 m) greatly increased (P < 0.05)in 7 days, 3 and 6 months after ablation respectively. There was a statistical difference between 7 days and 3 or 6 months after ablation in above-mentioned indexes (P < 0.05) except AHR (P > 0.05), no significant difference existed between 3 and 6 months in all indexes (P > 0.05). Conclusion: long-lasting atrial arrhythmia with rapid ventricular response could impair left ventricle function, which could be reversed within weeks after successful ablation and restoration of sinus rhythm.
文摘Causative mutations and variants associated with cardiac diseases have been found in genes encoding cardiac ion channels, accessory proteins, cytoskeletal components, junctional proteins, and signaling molecules. In most cases the functional evaluation of the genetic alterationhas been carried out by expressing the mutated proteins in in-vitro heterologous systems. While these studies have provided a wealth of functional details that have greatly enhanced the understanding of the pathological mechanisms, it has always been clear that heterologous expression of the mutant protein bears the intrinsic limitation of the lack of a proper intracellular environment and the lack of pathological remodeling. The results obtained from the application of the next generation sequencing technique to patients suffering from cardiac diseases have identified several loci, mostly in non-coding DNA regions, which still await functional analysis. The isolation and culture of human embryonic stem cells has initially provided a constant source of cells from which cardiomyocytes(CMs) can be obtained by differentiation. Furthermore, the possibility to reprogram cellular fate to a pluripotent state, has opened this process to the study of genetic diseases. Thus induced pluripotent stem cells(i PSCs) represent a completely new cellular model that overcomes the limitations of heterologous studies. Importantly, due to the possibility to keep spontaneously beating CMs in culture for several months, during which they show a certain degree of maturation/aging, this approach will also provide a system in which to address the effect of long-term expression of the mutated proteins or any other DNA mutation, in terms of electrophysiological remodeling. Moreover, since i PSC preserve the entire patients' genetic context, the system will help the physicians in identifying the most appropriate pharmacological intervention to correct the functional alteration. This article summarizes the current knowledge of cardiac genetic diseases modelled with i PSC.
文摘目的:基于CiteSpace知识图谱探讨近10年脓毒症心肌病(SICM)的研究现状和研究热点。方法:通过Web of Science检索2012—2022年6月SICM相关文献,应用文献计量学研究方法和CiteSpace软件对SICM文献的产出数量、国家/地区、研究机构、发文作者和共被引作者及双图叠加共被引期刊网络、关键词时间线网络和共被引文献网络进行文献计量学分析和可视化展示,探讨SICM研究现状和研究热点。结果:共纳入3814篇文献,近10年SICM相关文献逐年增长,2016年开始文献产出激增。从国家/地区、研究机构和作者发文频次角度,中国与欧美国家齐头并进,但是从论文影响力和共被引作者角度看,我国与欧美国家仍差距明显。近2年和近10年期刊共被引频次排名前10位的杂志相同,包括Crit Care Med、Crit Care等。SICM研究热点包括急性肾损伤、脓毒症心肌损伤、脓毒症休克、心源性休克、心肌梗死,涉及SICM的病因、病理机制、评估、治疗、并发症和预后。频次排名前10位的高被引文献主要为脓毒症的指南共识和随机对照试验及SICM研究综述。结论:基于CiteSpace对SICM文献进行计量学分析,可以更加清晰、直观地了解到全球SICM的研究现状,有助于总结该领域的研究现状,推动该领域的发展。
