The Experts below are selected from a list of 198 Experts worldwide ranked by ideXlab platform
Hideki Itoh - One of the best experts on this subject based on the ideXlab platform.
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a novel gain of function kcnj2 mutation associated with Short QT syndrome impairs inward rectification of kir2 1 currents
Cardiovascular Research, 2012Co-Authors: Tetsuhisa Hattori, Hideki Itoh, Takeru Makiyama, Masaharu Akao, Eiji Ehara, Seiko Ohno, Moritake Iguchi, Yukiko Nishio, Kenichi Sasaki, Masayuki YokodeAbstract:Aims Short-QT syndrome (SQTS) is a recently recognized disorder associated with atrial fibrillation (AF) and sudden death due to ventricular arrhythmias. Mutations in several ion channel genes have been linked to SQTS; however, the mechanism remains unclear. This study describes a novel heterozygous gain-of-function mutation in the inward rectifier potassium channel gene, KCNJ2 , identified in SQTS. Methods and results We studied an 8-year-old girl with a markedly Short-QT Interval (QT = 172 ms, QTc = 194 ms) who suffered from paroxysmal AF. Mutational analysis identified a novel heterozygous KCNJ2 mutation, M301K. Functional assays displayed no Kir2.1 currents when M301K channels were expressed alone. However, co-expression of wild-type (WT) with M301K resulted in larger outward currents than the WT at more than −30 mV. These results suggest a gain-of-function type modulation due to decreased inward rectification. Furthermore, we analysed the functional significance of the amino acid charge at M301 (neutral) by changing the residue. As with M301K, in M301R (positive), the homozygous channels were non-functional, whereas the heterozygous channels demonstrated decreased inward rectification. Meanwhile, the currents recorded in M301A (neutral) showed normal inward rectification under both homo- and heterozygous conditions. Heterozygous overexpression of WT and M301K in neonatal rat ventricular myocytes exhibited markedly Shorter action potential durations than the WT alone. Conclusion In this study, we identified a novel KCNJ2 gain-of-function mutation, M301K, associated with SQTS. Functional assays revealed no functional currents in the homozygous channels, whereas impaired inward rectification demonstrated under the heterozygous condition resulted in larger outward currents, which is a novel mechanism predisposing SQTS.
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clinical and electrocardiographic characteristics of patients with Short QT Interval in a large hospital based population
Heart Rhythm, 2012Co-Authors: Akashi Miyamoto, Hideki Hayashi, Tomohide Yoshino, Tamiro Kawaguchi, Atsushi Taniguchi, Hideki Itoh, Yoshihisa Sugimoto, Makoto Itoh, Takeru Makiyama, Joel Q XueAbstract:Background Short QT syndrome is one of the underlying disorders associated with ventricular fibrillation. However, the precise prognostic implication of a Short QT Interval remains unclear. Objective The purpose of this study was to investigate the prevalence and long-term prognosis in patients with a Shorter-than-normal QT Interval in a large hospital-based population. Methods We chose patients with a Short Bazett QTc Interval from a database consisting of 114,334 patients to determine the clinical characteristics and prognostic value of a Short QT Interval. Results A total of 427 patients (mean age 43.4 ± 22.4 years) had a Short QT Interval with about a 1.2 times higher male predominance (234 men). The QTc Interval was significantly longer in female than in male patients (363.8 ± 6.1 ms vs 357.1 ± 5.8 ms, P Conclusion The prevalence of a Short QT Interval showed a slight male preponderance and biphasic age-dependent distribution in both genders. The complication rate of atrial fibrillation was higher in those with a Short QT Interval than in general populations. The long-term outcome suggested that early repolarization in a Short QT Interval might be associated with potential risk of lethal arrhythmia.
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high prevalence of early repolarization in Short QT syndrome
Heart Rhythm, 2010Co-Authors: Hiroshi Watanabe, Hideki Itoh, Takeru Makiyama, Taku Koyama, Prince J Kannankeril, Shinji Seto, Kazuki Okamura, Masahiko Okada, Naohito Tanabe, Nobue YagiharaAbstract:Background Short QT syndrome (SQTS) is characterized by an abnormally Short QT Interval and sudden death. Due to the limited number of cases, the characteristics of SQTS are not well understood. It has been reported recently that early repolarization is associated with idiopathic ventricular fibrillation and the QT Interval is Short in patients with early repolarization. Objective The purpose of this study was to study the association between early repolarization and arrhythmic events in SQTS. Methods The study consisted of three cohorts: SQTS cohort (N = 37), control cohort with Short QT Interval and no arrhythmic events (N = 44), and control cohort with normal QT Interval (N = 185). ECG parameters were compared among the study cohorts. Results Heart rate, PR Interval, and QRS duration were similar among the three study cohorts. Early repolarization was more common in the SQTS cohort (65%) than in the Short QT control cohort (30%) and the normal QT control cohort (10%). Duration from T-wave peak to T-wave end was longer in the SQTS cohort than in the Short QT control cohort, although QT and corrected QT Intervals were similar. In the SQTS cohort, there were more males among patients with arrhythmic events than in those with a family history but without arrhythmic events. In multivariate models, early repolarization was associated with arrhythmic events in the SQTS cohort. ECG parameters including QT and QTc Intervals were not associated with arrhythmic events in the SQTS cohort. Conclusion There is a high prevalence of early repolarization in patients with SQTS. Early repolarization may be useful in identifying risk of cardiac events in SQTS.
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a novel kcnh2 mutation as a modifier for Short QT Interval
International Journal of Cardiology, 2009Co-Authors: Hideki Itoh, Tomoko Sakaguchi, Takashi Ashihara, W G Ding, Iori Nagaoka, Yuko Oka, Yuko Nakazawa, Takenori Yao, Makoto Ito, Kazufumi NakamuraAbstract:Abstract In a 34-year-old man showing Short QT Interval (QTc 329 ms), we identified a novel C-terminal KCNH2 mutation, R1135H. Using a heterologous expression system with CHO cells, the mutant channels were found to display a significantly slow deactivation, which resulted in a gain-of-function for reconstituted ‘ I Kr ' channels. This mutation could modify clinical phenotypes for this patient.
Ihor Gussak - One of the best experts on this subject based on the ideXlab platform.
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Short QT Interval in clinical practice
Journal of Electrocardiology, 2010Co-Authors: Preben Bjerregaard, Hari Nallapaneni, Ihor GussakAbstract:The last ten years have seen a growing interest in clinical scenarios, where a Short QT Interval may play a role, especially because of an increased risk of sudden cardiac death in some situations. One such entity is Short QT Syndrome, which has emerged as a rare, but very malignant disease, in particular when the QT Interval is very Short. A Short QT Interval has also been noticed in some patients with other arrhythmic syndromes such as Idiopathic Ventricular Fibrillation, Brugade Syndrome and Early Repolarization Syndrome, but the role of a Short QT Interval in these settings is so far not known. Hypercalcemia often leads to Shortening of the QT Interval, but there are no data in humans to suggest an increased risk of sudden cardiac death in this setting. In addition, a Shorter-than-usual QT Interval has been reported in patients with Chronic Fatigue Syndrome and in response to atropine, catecholamine and Hyperthermia. When a Short QT Interval is encountered in daily clinical practice, these various scenarios needs to be considered, but it is still not possible to come up with clear guidelines for how to work up and risk stratify such individuals. Genetic testing is only useful in very few and the value of an electrophysiologic study, Holter monitoring or stress testing to assess QT adaptation to heart rate and T wave morphology analysis may all be helpful, but not well-established, tests in this setting.
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Short QT syndrome
Annals of Noninvasive Electrocardiology, 2005Co-Authors: Preben Bjerregaard, Ihor GussakAbstract:Short QT syndrome (SQTS) is an inheritable primary electrical disease of the heart, discovered in 1999. It is characterized by an abnormally Short QT Interval (<300 ms) and a propensity to atrial fibrillation and sudden cardiac death (SCD). Like in the case of long QT syndrome there is more than one genetic mutation that can lead to a Short QT Interval in the ECG and so far two have been identified. Shortening of the effective refractory period combined with increased dispersion of repolarization is the likely substrate for reentry and life threatening tachyarrhythmias. Only 22 people have been classified as having SQTS: 15 from the actual measurement of a Short QT Interval in their ECG and 7 by history, all having died from SCD. It is very likely that several cases, especially among children, have been overlooked, since the Shortness of the QT Interval only becomes apparent at heart rates <80 beats/min. The best form of treatment is still not known, but prevention of atrial fibrillation has been accomplished by propafenone, and an implantable cardioverter defibrillator is recommended for prevention of SCD.
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Short QT syndrome mechanisms diagnosis and treatment
Nature Reviews Cardiology, 2005Co-Authors: Preben Bjerregaard, Ihor GussakAbstract:As yet, 22 cases of Short QT syndrome have been confirmed but other cases have probably been overlooked. This syndrome is a heritable primary electrical disease of the heart that can lead to atrial fibrillation and sudden cardiac death. The knowledge to date on this little recognized disorder is presented. Short QT syndrome is an inheritable primary electrical disease of the heart that was discovered in 1999. The disorder is characterized by an abnormally Short QT Interval (<300 ms) and a propensity to atrial fibrillation, sudden cardiac death or both. As in the case of long QT syndrome, more than one relevant genetic mutation has been identified that can lead to a Short QT Interval on electrocardiography; so far two have been identified. Shortening of the effective refractory period combined with increased dispersion of repolarization is the likely substrate for re-entry and life-threatening tachyarrhythmias. Thus far, 22 people have been classified as having Short QT syndrome: 15 from the actual measurement of a Short QT Interval on electrocardiograms and 7 by history after they died from sudden cardiac death. Several cases, especially among children, have probably been overlooked, since the Shortness of the QT Interval becomes apparent only at heart rates less than 80 beats/min. The best form of treatment is still unknown, but prevention of atrial fibrillation has been accomplished by propafenone. Implantation of an implantable cardioverter defibrillator is recommended for prevention of sudden cardiac death.
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Short QT Interval
2003Co-Authors: Ihor Gussak, Charles Antzelevitch, Daniel Goodman, Preben BjerregaardAbstract:Although many factors influence the duration of ventricular repolarization and the detailed appearance of ECG (Table 1), regional differences in the configuration of action potentials across the myocardial wall are considered to be major determinants of the three-dimensional pattern of ECG waves and Intervals. The QT Interval is a surrogate electrocardiographic index of ventricular repolarization. Its duration under normal conditions is mainly determined by expression, properties, and balance of the repolarizing forces inward sodium and calcium, and outward potassium and chloride currents (intrinsic cardiac properties).
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idiopathic Short QT Interval a new clinical syndrome
The Cardiology, 2000Co-Authors: Ihor Gussak, Josep Brugada, Pedro Brugada, Scott R Wright, Stephen L Kopecky, Bernard R Chaitman, Preben BjerregaardAbstract:In this first clinical report of an idiopathic familial persistently Short QT Interval (QTI), we describe three members of one family (a 17-year-old female, her 21-year-old brother, and their 51-year-old mother) demonstrating this ECG phenomenon, associated in the 17-year-old with several episodes of paroxysmal atrial fibrillation requiring electrical cardioversion. Similar ECG changes seen in an unrelated 37-year-old patient were associated with sudden cardiac death. Our report also describes other manifestations of abnormal Shortening of the QTI and considers the possible arrhythmogenic potential of the Short QTI.
Takeru Makiyama - One of the best experts on this subject based on the ideXlab platform.
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a novel gain of function kcnj2 mutation associated with Short QT syndrome impairs inward rectification of kir2 1 currents
Cardiovascular Research, 2012Co-Authors: Tetsuhisa Hattori, Hideki Itoh, Takeru Makiyama, Masaharu Akao, Eiji Ehara, Seiko Ohno, Moritake Iguchi, Yukiko Nishio, Kenichi Sasaki, Masayuki YokodeAbstract:Aims Short-QT syndrome (SQTS) is a recently recognized disorder associated with atrial fibrillation (AF) and sudden death due to ventricular arrhythmias. Mutations in several ion channel genes have been linked to SQTS; however, the mechanism remains unclear. This study describes a novel heterozygous gain-of-function mutation in the inward rectifier potassium channel gene, KCNJ2 , identified in SQTS. Methods and results We studied an 8-year-old girl with a markedly Short-QT Interval (QT = 172 ms, QTc = 194 ms) who suffered from paroxysmal AF. Mutational analysis identified a novel heterozygous KCNJ2 mutation, M301K. Functional assays displayed no Kir2.1 currents when M301K channels were expressed alone. However, co-expression of wild-type (WT) with M301K resulted in larger outward currents than the WT at more than −30 mV. These results suggest a gain-of-function type modulation due to decreased inward rectification. Furthermore, we analysed the functional significance of the amino acid charge at M301 (neutral) by changing the residue. As with M301K, in M301R (positive), the homozygous channels were non-functional, whereas the heterozygous channels demonstrated decreased inward rectification. Meanwhile, the currents recorded in M301A (neutral) showed normal inward rectification under both homo- and heterozygous conditions. Heterozygous overexpression of WT and M301K in neonatal rat ventricular myocytes exhibited markedly Shorter action potential durations than the WT alone. Conclusion In this study, we identified a novel KCNJ2 gain-of-function mutation, M301K, associated with SQTS. Functional assays revealed no functional currents in the homozygous channels, whereas impaired inward rectification demonstrated under the heterozygous condition resulted in larger outward currents, which is a novel mechanism predisposing SQTS.
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clinical and electrocardiographic characteristics of patients with Short QT Interval in a large hospital based population
Heart Rhythm, 2012Co-Authors: Akashi Miyamoto, Hideki Hayashi, Tomohide Yoshino, Tamiro Kawaguchi, Atsushi Taniguchi, Hideki Itoh, Yoshihisa Sugimoto, Makoto Itoh, Takeru Makiyama, Joel Q XueAbstract:Background Short QT syndrome is one of the underlying disorders associated with ventricular fibrillation. However, the precise prognostic implication of a Short QT Interval remains unclear. Objective The purpose of this study was to investigate the prevalence and long-term prognosis in patients with a Shorter-than-normal QT Interval in a large hospital-based population. Methods We chose patients with a Short Bazett QTc Interval from a database consisting of 114,334 patients to determine the clinical characteristics and prognostic value of a Short QT Interval. Results A total of 427 patients (mean age 43.4 ± 22.4 years) had a Short QT Interval with about a 1.2 times higher male predominance (234 men). The QTc Interval was significantly longer in female than in male patients (363.8 ± 6.1 ms vs 357.1 ± 5.8 ms, P Conclusion The prevalence of a Short QT Interval showed a slight male preponderance and biphasic age-dependent distribution in both genders. The complication rate of atrial fibrillation was higher in those with a Short QT Interval than in general populations. The long-term outcome suggested that early repolarization in a Short QT Interval might be associated with potential risk of lethal arrhythmia.
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high prevalence of early repolarization in Short QT syndrome
Heart Rhythm, 2010Co-Authors: Hiroshi Watanabe, Hideki Itoh, Takeru Makiyama, Taku Koyama, Prince J Kannankeril, Shinji Seto, Kazuki Okamura, Masahiko Okada, Naohito Tanabe, Nobue YagiharaAbstract:Background Short QT syndrome (SQTS) is characterized by an abnormally Short QT Interval and sudden death. Due to the limited number of cases, the characteristics of SQTS are not well understood. It has been reported recently that early repolarization is associated with idiopathic ventricular fibrillation and the QT Interval is Short in patients with early repolarization. Objective The purpose of this study was to study the association between early repolarization and arrhythmic events in SQTS. Methods The study consisted of three cohorts: SQTS cohort (N = 37), control cohort with Short QT Interval and no arrhythmic events (N = 44), and control cohort with normal QT Interval (N = 185). ECG parameters were compared among the study cohorts. Results Heart rate, PR Interval, and QRS duration were similar among the three study cohorts. Early repolarization was more common in the SQTS cohort (65%) than in the Short QT control cohort (30%) and the normal QT control cohort (10%). Duration from T-wave peak to T-wave end was longer in the SQTS cohort than in the Short QT control cohort, although QT and corrected QT Intervals were similar. In the SQTS cohort, there were more males among patients with arrhythmic events than in those with a family history but without arrhythmic events. In multivariate models, early repolarization was associated with arrhythmic events in the SQTS cohort. ECG parameters including QT and QTc Intervals were not associated with arrhythmic events in the SQTS cohort. Conclusion There is a high prevalence of early repolarization in patients with SQTS. Early repolarization may be useful in identifying risk of cardiac events in SQTS.
John M. Canty - One of the best experts on this subject based on the ideXlab platform.
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Reply to "Letter to the editor: 'The role of Short QT Interval and elevated LV end-diastolic pressure in the genesis of ventricular tachycardia and fibrillation'".
American journal of physiology. Heart and circulatory physiology, 2013Co-Authors: Matthew F. Pizzuto, Suzuki, Michael D. Banas, Brendan M. Heavey, James A. Fallavollita, John M. CantyAbstract:reply: We appreciate Dr. Karagueuzian's ([3][1]) insight regarding the potential role of reduced cytosolic ATP (derived from glucose and glycogen) in explaining Shortening of the QT Interval (through activation of the ATP-sensitive K+ channel) as well as elevations in end-diastolic pressure (through
Preben Bjerregaard - One of the best experts on this subject based on the ideXlab platform.
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Short QT Interval in clinical practice
Journal of Electrocardiology, 2010Co-Authors: Preben Bjerregaard, Hari Nallapaneni, Ihor GussakAbstract:The last ten years have seen a growing interest in clinical scenarios, where a Short QT Interval may play a role, especially because of an increased risk of sudden cardiac death in some situations. One such entity is Short QT Syndrome, which has emerged as a rare, but very malignant disease, in particular when the QT Interval is very Short. A Short QT Interval has also been noticed in some patients with other arrhythmic syndromes such as Idiopathic Ventricular Fibrillation, Brugade Syndrome and Early Repolarization Syndrome, but the role of a Short QT Interval in these settings is so far not known. Hypercalcemia often leads to Shortening of the QT Interval, but there are no data in humans to suggest an increased risk of sudden cardiac death in this setting. In addition, a Shorter-than-usual QT Interval has been reported in patients with Chronic Fatigue Syndrome and in response to atropine, catecholamine and Hyperthermia. When a Short QT Interval is encountered in daily clinical practice, these various scenarios needs to be considered, but it is still not possible to come up with clear guidelines for how to work up and risk stratify such individuals. Genetic testing is only useful in very few and the value of an electrophysiologic study, Holter monitoring or stress testing to assess QT adaptation to heart rate and T wave morphology analysis may all be helpful, but not well-established, tests in this setting.
-
Short QT syndrome
Annals of Noninvasive Electrocardiology, 2005Co-Authors: Preben Bjerregaard, Ihor GussakAbstract:Short QT syndrome (SQTS) is an inheritable primary electrical disease of the heart, discovered in 1999. It is characterized by an abnormally Short QT Interval (<300 ms) and a propensity to atrial fibrillation and sudden cardiac death (SCD). Like in the case of long QT syndrome there is more than one genetic mutation that can lead to a Short QT Interval in the ECG and so far two have been identified. Shortening of the effective refractory period combined with increased dispersion of repolarization is the likely substrate for reentry and life threatening tachyarrhythmias. Only 22 people have been classified as having SQTS: 15 from the actual measurement of a Short QT Interval in their ECG and 7 by history, all having died from SCD. It is very likely that several cases, especially among children, have been overlooked, since the Shortness of the QT Interval only becomes apparent at heart rates <80 beats/min. The best form of treatment is still not known, but prevention of atrial fibrillation has been accomplished by propafenone, and an implantable cardioverter defibrillator is recommended for prevention of SCD.
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Short QT syndrome mechanisms diagnosis and treatment
Nature Reviews Cardiology, 2005Co-Authors: Preben Bjerregaard, Ihor GussakAbstract:As yet, 22 cases of Short QT syndrome have been confirmed but other cases have probably been overlooked. This syndrome is a heritable primary electrical disease of the heart that can lead to atrial fibrillation and sudden cardiac death. The knowledge to date on this little recognized disorder is presented. Short QT syndrome is an inheritable primary electrical disease of the heart that was discovered in 1999. The disorder is characterized by an abnormally Short QT Interval (<300 ms) and a propensity to atrial fibrillation, sudden cardiac death or both. As in the case of long QT syndrome, more than one relevant genetic mutation has been identified that can lead to a Short QT Interval on electrocardiography; so far two have been identified. Shortening of the effective refractory period combined with increased dispersion of repolarization is the likely substrate for re-entry and life-threatening tachyarrhythmias. Thus far, 22 people have been classified as having Short QT syndrome: 15 from the actual measurement of a Short QT Interval on electrocardiograms and 7 by history after they died from sudden cardiac death. Several cases, especially among children, have probably been overlooked, since the Shortness of the QT Interval becomes apparent only at heart rates less than 80 beats/min. The best form of treatment is still unknown, but prevention of atrial fibrillation has been accomplished by propafenone. Implantation of an implantable cardioverter defibrillator is recommended for prevention of sudden cardiac death.
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Short QT Interval
2003Co-Authors: Ihor Gussak, Charles Antzelevitch, Daniel Goodman, Preben BjerregaardAbstract:Although many factors influence the duration of ventricular repolarization and the detailed appearance of ECG (Table 1), regional differences in the configuration of action potentials across the myocardial wall are considered to be major determinants of the three-dimensional pattern of ECG waves and Intervals. The QT Interval is a surrogate electrocardiographic index of ventricular repolarization. Its duration under normal conditions is mainly determined by expression, properties, and balance of the repolarizing forces inward sodium and calcium, and outward potassium and chloride currents (intrinsic cardiac properties).
-
idiopathic Short QT Interval a new clinical syndrome
The Cardiology, 2000Co-Authors: Ihor Gussak, Josep Brugada, Pedro Brugada, Scott R Wright, Stephen L Kopecky, Bernard R Chaitman, Preben BjerregaardAbstract:In this first clinical report of an idiopathic familial persistently Short QT Interval (QTI), we describe three members of one family (a 17-year-old female, her 21-year-old brother, and their 51-year-old mother) demonstrating this ECG phenomenon, associated in the 17-year-old with several episodes of paroxysmal atrial fibrillation requiring electrical cardioversion. Similar ECG changes seen in an unrelated 37-year-old patient were associated with sudden cardiac death. Our report also describes other manifestations of abnormal Shortening of the QTI and considers the possible arrhythmogenic potential of the Short QTI.