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Introduction: KCNQ1 and KCNE1 form slowly activating delayed rectifier potassium currents (IKs). Loss-of-function of IKs by KCNQ1 variants causes type-1 long QT syndrome (LQTS). Also, some KCNQ1 variants are reported to cause epilepsy. Segment 4 (S4) of voltage-gated potassium channels has several positively-charged amino acids that are periodically aligned, and acts as a voltage-sensor. Intriguingly, KCNQ1 has a neutral-charge glutamine at the third position (Q3) in the S4 (Q234 position in KCNQ1), which suggests that the Q3 (Q234) may play an important role in the gating properties of IKs. We identified a novel KCNQ1 Q234K (substituted for a positively-charged lysine) variant in patients (a girl and her mother) with LQTS and epileptiform activity on electroencephalogram. The mother had been diagnosed with epilepsy. Therefore, we sought to elucidate the effects of the KCNQ1 Q234K on gating properties of IKs. Methods: Wild-type (WT)-KCNQ1 and/or Q234K-KCNQ1 were transiently expressed in tsA201-cells with KCNE1 (E1) (WT + E1-channels, Q234K + E1-channels, and WT + Q234K + E1-channels), and membrane currents were recorded using whole-cell patch-clamp techniques. Results: At 8-s depolarization, current density (CD) of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly larger than the WT + E1-channels (WT + E1: 701 ± 59 pA/pF; Q234K + E1: 912 ± 50 pA/pF, p < 0.01; WT + Q234K + E1: 867 ± 48 pA/pF, p < 0.05). Voltage dependence of activation (VDA) of the Q234K + E1-channels or WT + Q234K + E1-channels was slightly but significantly shifted to depolarizing potentials in comparison to the WT + E1-channels ([V1/2] WT + E1: 25.6 ± 2.6 mV; Q234K + E1: 31.8 ± 1.7 mV, p < 0.05; WT + Q234K + E1: 32.3 ± 1.9 mV, p < 0.05). Activation rate of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly delayed in comparison to the WT + E1-channels ([half activation time] WT + E1: 664 ± 37 ms; Q234K + E1: 1,417 ± 60 ms, p < 0.01; WT + Q234K + E1: 1,177 ± 71 ms, p < 0.01). At 400-ms depolarization, CD of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly decreased in comparison to the WT + E1-channels (WT + E1: 392 ± 42 pA/pF; Q234K + E1: 143 ± 12 pA/pF, p < 0.01; WT + Q234K + E1: 209 ± 24 pA/pF, p < 0.01) due to delayed activation rate and depolarizing shift of VDA. Conclusion: The KCNQ1 Q234K induced IKs gain-of-function during long (8-s)-depolarization, while loss of-function during short (400-ms)-depolarization, which indicates that the variant causes LQTS, and raises a possibility that the variant may also cause epilepsy. Our data provide novel insights into the functional consequences of charge addition on the Q3 in the S4 of KCNQ1.
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Background: Atrioventricular nodal reentrant tachycardia (AVNRT) sometimes recurs even after anatomical slow pathway (SP) ablation targeting the rightward inferior extension (RIE). This multicenter study aimed to determine the reasons for AVNRT recurrence. Methods and Results: Forty-six patients were treated successfully for recurrent AVNRT. Initial treatment was for 38 slow-fast AVNRTs, 3 fast-slow AVNRTs, 2 slow-slow AVNRTs, 2 slow-fast and fast-slow AVNRTs, and 1 noninducible AVNRT. All initial treatments were of RF application to the RIE; SP elimination was achieved in 11, dual AVN physiology was seen in 29, and AVNRT remained inducible in 5. The recurrent AVNRTs included 34 slow-fast AVNRTs, 6 fast-slow AVNRTs, 3 slow-slow AVNRTs, 2 slow-fast and fast-slow AVNRTs, and 1 slow-fast and slow-slow AVNRTs. Successful ablation site was within the RIE in 39 and left inferior extension in 7. In 30 of 39, the successful RIE site was in the same area or higher than that of the initial procedure. Conclusion: For a high majority (around 85%) of patients in whom AVNRT recurs after initial ablation success, the site of a second successful procedure will be within the RIE even though the RIE was originally targeted. Furthermore, a high majority (around 86%) of sites of successful ablation will be higher than those originally targeted.
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Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Conversely, RyR2 loss-of-function mutations cause a new disease entity, termed calcium release deficiency syndrome (CRDS), which may include RYR2-related long QT syndrome (LQTS). Importantly, unlike CPVT, patients with CRDS do not always exhibit exercise- or epinephrine-induced ventricular arrhythmias, which precludes a diagnosis of CRDS. Here we report a boy and his father, who both experienced exercise-induced cardiac events and harbor the same RYR2 E4107A variant. In the boy, an exercise stress test (EST) and epinephrine provocation test (EPT) did not induce any ventricular arrhythmias. QTc was slightly prolonged (QTc: 474 ms), and an EPT induced QTc prolongation (QTc-baseline: 466 ms, peak: 532 ms, steady-state: 527 ms). In contrast, in his father, QTc was not prolonged (QTc: 417 ms), and neither an EST nor EPT induced QTc prolongation. However, an EST induced multifocal premature ventricular contraction (PVC) bigeminy and bidirectional PVC couplets. Thus, they exhibited distinct clinical phenotypes: the boy exhibited LQTS (or CRDS) phenotype, whereas his father exhibited CPVT phenotype. These findings suggest that, in addition to the altered RyR2 function, other unidentified factors, such as other genetic, epigenetic, and environmental factors, and aging, may be involved in the diverse phenotypic manifestations. Considering that a single RYR2 variant can cause both CPVT and LQTS (or CRDS) phenotypes, in cascade screening of patients with CPVT and CRDS, an EST and EPT are not sufficient and genetic analysis is required to identify individuals who are at increased risk for life-threatening arrhythmias.
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Síndrome de QT Prolongado , Fenotipo , Canal Liberador de Calcio Receptor de Rianodina , Taquicardia Ventricular , Humanos , Canal Liberador de Calcio Receptor de Rianodina/genética , Masculino , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/diagnóstico , Taquicardia Ventricular/genética , Taquicardia Ventricular/diagnóstico , Electrocardiografía , Linaje , Adulto , Prueba de Esfuerzo , MutaciónRESUMEN
Background: This study aimed to establish a systematic method for diagnosing atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander concealed nodoventricular pathway (cNVP). Methods: We analyzed 13 cases of AVNRT with a bystander cNVP, 11 connected to the slow pathway (cNVP-SP) and two to the fast pathway (cNVP-FP), along with two cases of cNVP-related orthodromic reciprocating tachycardia (ORT). Results: The diagnostic process was summarized in three steps. Step 1 was identification of the presence of an accessory pathway by resetting the tachycardia with delay (n = 9) and termination without atrial capture (n = 4) immediately after delivery of a His-refractory premature ventricular contraction (PVC). Step 2 was exclusion of ORT by atrio-His block during the tachycardia (n = 4), disappearance of the reset phenomenon after the early PVC (n = 7), or dissociation of His from the tachycardia during ventricular overdrive pacing (n = 1). Moreover, tachycardia reset/termination without the atrial capture (n = 2/2) 1 cycle after the His-refractory PVC was specifically diagnostic. Exceptionally, the disappearance of the reset phenomenon was also observed in the two cNVP-ORTs. Step 3 was verification of the AVN as the cNVP insertion site, evidenced by an atrial reset/block preceding the His reset/block in fast-slow AVNRT with a cNVP-SP and slow-fast AVNRT with a cNVP-FP or His reset preceding the atrial reset in slow-fast AVNRT with a cNVP-SP. Conclusion: AVNRT with a bystander cNVP can be diagnosed in the three steps with few exceptions. Notably, tachycardia reset/termination without atrial capture one cycle after delivery of a His-refractory PVC is specifically diagnostic.
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BACKGROUND: A 70-year-old man revealed a rare type of atrioventricular nodal re-entrant tachycardia (AVNRT) involving distinct retrograde pathways, superior slow pathway, and inferolateral left atrial slow pathway. RESULT: Radiofrequency ablation was successfully performed on the noncoronary cusp and in the left atrium, respectively, to eliminate the tachycardias. DISCUSSION AND CONCLUSION: Due to the anomalous electrical conduction patterns, careful diagnosis and ablation strategies were necessary to avoid the risk of atrioventricular block. These findings underscore the diversity and complexity of AVNRT and highlight the importance of tailored therapeutic approaches.
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Fibrilación Atrial , Ablación por Catéter , Taquicardia por Reentrada en el Nodo Atrioventricular , Masculino , Humanos , Anciano , Taquicardia por Reentrada en el Nodo Atrioventricular/diagnóstico , Taquicardia por Reentrada en el Nodo Atrioventricular/cirugía , Fibrilación Atrial/cirugía , Electrocardiografía , Fascículo Atrioventricular , Atrios CardíacosRESUMEN
AIMS: Patients with particular mutations of type-2 long QT syndrome (LQT2) are at an increased risk for malignant arrhythmia during fever. This study aimed to determine the mechanism by which KCNH2 mutations cause fever-induced QT prolongation and torsades de pointes (TdP). METHODS AND RESULTS: We evaluated three KCNH2 mutations, G584S, D609G, and T613M, in the Kv11.1 S5-pore region, identified in patients with marked QT prolongation and TdP during fever. We also evaluated KCNH2 M124T and R269W, which are not associated with fever-induced QT prolongation. We characterized the temperature-dependent changes in the electrophysiological properties of the mutant Kv11.1 channels by patch-clamp recording and computer simulation. The average tail current densities (TCDs) at 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller and less increased with rising temperature from 35°C to 40°C than those for WT, M124T, and R269W. The ratios of the TCDs at 40°C to 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller than for WT, M124T, and R269W. The voltage dependence of the steady-state inactivation curve for WT, M124T, and R269W showed a significant positive shift with increasing temperature; however, that for G584S, WT+D609G, and WT+T613M showed no significant change. Computer simulation demonstrated that G584S, WT+D609G, and WT+T613M caused prolonged action potential durations and early afterdepolarization formation at 40°C. CONCLUSION: These findings indicate that KCNH2 G584S, D609G, and T613M in the S5-pore region reduce the temperature-dependent increase in TCDs through an enhanced inactivation, resulting in QT prolongation and TdP at a febrile state in patients with LQT2.
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Síndrome de QT Prolongado , Torsades de Pointes , Humanos , Torsades de Pointes/diagnóstico , Torsades de Pointes/genética , Simulación por Computador , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/genética , Mutación , Proteínas de Unión al ADN , Canal de Potasio ERG1/genéticaAsunto(s)
Ablación por Catéter , Taquicardia por Reentrada en el Nodo Atrioventricular , Humanos , Taquicardia por Reentrada en el Nodo Atrioventricular/diagnóstico , Taquicardia por Reentrada en el Nodo Atrioventricular/cirugía , Fascículo Atrioventricular , Nodo Atrioventricular/cirugía , ElectrocardiografíaRESUMEN
Supraventricular tachycardia (SVT) with ventriculoatrial (VA) block can represent a diagnostic challenge. We present a case of SVT where His-His interval shortening was repeatedly observed during episodes of VA block. This novel observation is more diagnostically suggestive of atrioventricular nodal re-entrant tachycardia, as opposed to orthodromic re-entry using a nodofascicular or nodoventricular pathway where a constant His-His is recorded during episodes of VA block. (Level of Difficulty: Intermediate.).
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BACKGROUND: In adult patients, subcutaneous implantable cardioverter defibrillators (S-ICDs) have been reported to be non-inferior to transvenous ICDs with respect to the incidence of device-related complications and inappropriate shocks. Only a few reports have investigated the efficacy of S-ICDs in the pediatric field. This study aimed to investigate the utility and safety of S-ICDs in patients ≤18 years old. METHODS: This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients <18 years old who underwent S-ICD implantations were enrolled. The detailed data on the device implantations and eligibility tests, incidence of appropriate- and inappropriate shocks, and follow-up data were assessed. RESULTS: A total of 62 patients were enrolled from 30 centers. The patients ranged in age from 3 to 18 (median 14 years old [IQR 11.0-16.0 years]). During a median follow up of 27 months (13.3-35.8), a total of 16 patients (26.2%) received appropriate shocks and 13 (21.3%) received inappropriate shocks. The common causes of the inappropriate shocks were sinus tachycardia (n = 4, 30.8%) and T-wave oversensing (n = 4, 30.8%). In spite of the physical growth, the number of suitable sensing vectors did not change during the follow up. No one had any lead fractures or device infections in the chronic phase. CONCLUSIONS: Our study suggested that S-ICDs can prevent sudden cardiac death in the pediatric population with a low incidence of lead complications or device infections. The number of suitable sensing vectors did not change during the patients' growth.
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Desfibriladores Implantables , Adulto , Humanos , Niño , Adolescente , Estudios Retrospectivos , Resultado del Tratamiento , Desfibriladores Implantables/efectos adversos , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/prevención & control , Arritmias CardíacasRESUMEN
An 81-year-old man was admitted to the hospital because of decreased level of consciousness. He had bradycardia (27 beats/min). Electrocardiography showed ST-segment elevation in leads II, III, and aVF and ST-segment depression in leads aVL, V1. Transthoracic echocardiography (TTE) visualized reduced motion of the left ventricular (LV) inferior wall and right ventricular (RV) free wall. Coronary angiography revealed occlusion of the right coronary artery. A primary percutaneous coronary intervention was successfully performed with temporary pacemaker backup. On the third day, the sinus rhythm recovered, and the temporary pacemaker was removed. On the fifth day, a sudden cardiac arrest occurred. Extracorporeal cardiopulmonary resuscitation was performed. TTE showed a high-echoic effusion around the right ventricle, indicating a hematoma. The drainage was ineffective. He died on the eighth day. An autopsy showed the infarcted lesion and an intramural hematoma in the RV. However, no definite perforation of the myocardium was detected. The hematoma extended to the epicardium surface, indicative of oozing-type RV rupture induced by RV infarction. The oozing-type rupture induced by RV infarction might develop asymptomatically without influence on the vital signs of the patient. Frequent echocardiographic evaluation is essential in cases of RV infarction taking care of silent oozing-type rupture. Learning objective: Inferior left ventricular infarction sometimes complicates right ventricular (RV) infarction. The typical manifestations of RV infarction include low blood pressure, low cardiac output, and elevated right atrium pressure. Although the frequency is low, fatal complications of oozing-type RV rupture might progress asymptomatically. Frequent echocardiographic screening is necessary to detect them.
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Neoplasias Cardíacas , Hemangioma , Leiomiomatosis , Neoplasias Uterinas , Neoplasias Vasculares , Humanos , Femenino , Leiomiomatosis/diagnóstico por imagen , Vena Cava Inferior/diagnóstico por imagen , Ecocardiografía , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Cardíacas/diagnóstico por imagen , Atrios Cardíacos/diagnóstico por imagenRESUMEN
BACKGROUND: Gain-of-function mutations in CACNA1C encoding Cav1.2 cause syndromic or non-syndromic type-8 long QT syndrome (LQTS) (sLQT8 or nsLQT8). The cytoplasmic domain (D)â -â ¡ linker in Cav1.2 plays a pivotal role in calcium channel inactivation, and mutations in this site have been associated with sLQT8 (such as Timothy syndrome) but not nsLQT8. OBJECTIVE: Since we identified a novel CACNA1C mutation, located in the Dâ -â ¡ linker, associated with nsLQTS, we sought to reveal its biophysical defects. METHODS: Target panel sequencing was employed in 24 genotype-negative nsLQTS probands (after Sanger sequencing) and three family members. Wild-type (WT) or R511Q Cav1.2 was transiently expressed in tsA201 cells, then whole-cell Ca2+ or Ba2+ currents (ICa or IBa) were recorded using whole-cell patch-clamp techniques. RESULTS: We identified two CACNA1C mutations, a previously reported R858H mutation and a novel R511Q mutation located in the Dâ -â ¡ linker. Four members of one nsLQTS family harbored the CACNA1C R511Q mutation. The current density and steady-state activation were comparable to those of WT-ICa. However, persistent currents in R511Q-ICa were significantly larger than those of WT-ICa (WT at +20 mV: 3.3±0.3%, R511Q: 10.8±0.8%, P<0.01). The steady-state inactivation of R511Q-ICa was weak in comparison to that of WT-ICa at higher prepulse potentials, resulting in increased window currents in R511Q-ICa. Slow component of inactivation of R511Q-ICa was significantly delayed compared to that of WT-ICa (WT-tau at +20 mV: 81.3±3.3 ms, R511Q-tau: 125.1±5.0 ms, P<0.01). Inactivation of R511Q-IBa was still slower than that of WT-IBa, indicating that voltage-dependent inactivation (VDI) of R511Q-ICa was predominantly delayed. CONCLUSIONS: Delayed VDI, increased persistent currents, and increased window currents of R511Q-ICa cause nsLQT8. Our data provide novel insights into the structure-function relationships of Cav1.2 and the pathophysiological roles of the Dâ -â ¡ linker in phenotypic manifestations.
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Canales de Calcio Tipo L , Síndrome de QT Prolongado , Canales de Calcio Tipo L/genética , Humanos , Síndrome de QT Prolongado/genética , MutaciónRESUMEN
INTRODUCTION: The electrophysiological discrimination between fast-slow (F/S-) atrioventricular (AV) nodal reentrant tachycardia (NRT) and atrial tachycardia (AT) originating from the interatrial septum remains challenging. While a V-A-A-V response may occur immediately after ventricular induction or entrainment of either tachycardia, the electrophysiological dissimilarities in that response between the two tachycardias remain unclear. The purpose of this study was to identify a diagnostic indicator discriminating F/S-AVNRT from AT by examining the difference in the V-A-A-V response between the two tachycardias. METHODS: This retrospective study included 17 patients with F/S-AVNRT [seven with common-form F/S-AVNRT using a typical slow pathway (SP) and 10 with superior type F/S-AVNRT using a superior SP] and 10 patients with reentrant AT. All 27 patients presented with long RP supraventricular tachycardia and an initial V-A-A-V response upon ventricular induction or entrainment. The V-A-A-V response in patients with F/S-AVNRT was due to dual atrial responses. We measured the interval between the first (A1) and second atrial electrogram (A2) of V-A-A-V and calculated ΔAA by subtracting A1-A2 from the tachycardia cycle length. RESULTS: V-A-A-V responses were observed most often upon ventricular induction of F/S-AVNRT (6 ± 5 times) as well as AT (6 ± 6 times; p = .87). The V-A-A-V response upon ventricular entrainment was observed in a single patient with F/S-AVNRT versus 10 all patients with AT (p < .001). ΔAA ranged between -80 and 228 ms in F/S-AVNRT and between -184 and 26 ms in AT. A ΔAA > 26 ms predicted a diagnosis of F/S-AVNRT with a 76% sensitivity and 100% specificity, while a ΔAA <-80 ms predicted a diagnosis of AT with a 50% sensitivity and 100% specificity. CONCLUSIONS: ΔAA is a useful, confirmatory, diagnostic indicator of F/S-AVNRT versus AT associated with the V-A-A-V response.
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Taquicardia por Reentrada en el Nodo Atrioventricular , Taquicardia Paroxística , Taquicardia Supraventricular , Fascículo Atrioventricular , Humanos , Estudios Retrospectivos , Taquicardia por Reentrada en el Nodo Atrioventricular/diagnóstico , Taquicardia Paroxística/diagnósticoAsunto(s)
Taquicardia por Reentrada en el Nodo Atrioventricular/diagnóstico , Taquicardia Ectópica de Unión/diagnóstico , Estimulación Cardíaca Artificial , Ablación por Catéter , Diagnóstico Diferencial , Electrocardiografía , Femenino , Humanos , Persona de Mediana Edad , Taquicardia por Reentrada en el Nodo Atrioventricular/fisiopatología , Taquicardia por Reentrada en el Nodo Atrioventricular/cirugía , Taquicardia Ectópica de Unión/fisiopatología , Taquicardia Ectópica de Unión/cirugíaRESUMEN
According to guidelines, carbon-ion beam therapy is considered to carry a high safety risk for patients with cardiac implantable electronic devices (CIEDs), although the actual impacts remain unclear. In this study, we investigated the safety of carbon-ion beam therapy in patients with CIEDs. Patients with CIEDs who underwent carbon-ion therapy at Gunma University Heavy Ion Medical Center between June 2010 and December 2019 were identified and investigated for abnormalities in the operation of their CIEDs, such as oversensing and resetting during irradiation, and abnormalities in operation after treatment. In addition, the risk of irradiation from carbon-ion beam therapy was evaluated by model simulations. Twenty patients (22 sites) with CIEDs were identified, 19 with pacemakers and one with an implantable cardioverter-defibrillator (ICD). Treatments were completed without any problems, except for one case in which the treatment was discontinued because of worsening of the primary disease. Monte Carlo simulation indicated that the carbon beam irradiation produced neutrons at a constant and high level in the irradiation field. Nevertheless, with the distances between the CIEDs and the irradiation fields in the analyzed cases, the quantity of neutrons at the CIEDs was lower than that within the irradiation. Although carbon-ion beam therapy can be safely administered to patients with CIEDs, it is advisable to perform the therapy with sufficient preparation and backup devices because of the risks involved.
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Desfibriladores Implantables , Radioterapia de Iones Pesados , Marcapaso Artificial , Carbono/uso terapéutico , Desfibriladores Implantables/efectos adversos , Electrónica , HumanosRESUMEN
Recently, new vaccine platforms-including mRNA vaccines for coronavirus disease 2019 (COVID-19) have been given emergency use authorization in Japan. Here, we present a rare case of myocarditis following a COVID-19 vaccine. In this case, myocarditis was confirmed by cardiac magnetic resonance imaging, endomyocardial biopsy, and troponin levels. The degree of myocardial inflammation in the endomyocardial biopsy samples was mild and the patient's clinical course was not severe. Although the pathology of myocarditis in this case was mild, further investigation would be needed.