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The physical function of older patients with heart failure (HF) is likely to decline, and the Short Physical Performance Battery (SPPB) is widely used for its evaluation. No study has analyzed the SPPB by using Rasch model in these patients. The aim of this study was to examine the structural validity and item response of the SPPB in older inpatients with HF.In this multicenter cross-sectional study, we investigated 106 older inpatients with HF. We evaluated the SPPB's rating scale structure, unidimensionality, and measurement accuracy (0 = poor performance to 4 = normal performance).The SPPB rating scale fulfilled the category functioning criteria. All items fit the underlying scale construct. The SPPB demonstrated adequate reliability (person reliability = 0.81) and separated persons into four strata: those with very low, low, moderate, and high physical performance. Item-difficulty measures were -0.59 to 0.96 logits, and regarding the person ability-item difficulty matching for the SPPB, the item was somewhat easy (the mean of person ability = 0.89 logits; mean of item difficulty = 0.00).The SPPB has strong measurement properties and is an appropriate scale for quantitatively evaluating physical function in older patients with HF.For older adults with heart failure (HF), the Short Physical Performance Battery (SPPB) is often used to measure physical performance.Rasch analysis revealed that SPPB had strong measurement properties in older adults with HF.This result may help rehabilitation professionals use the SPPB as a physical performance scale in clinical practice to aid decision-making in intervention planning.

[Purpose] To clarify the relationship between lower extremity function and activities of daily living and characterize lower extremity function in hospitalized middle-aged and older adults with subacute cardiovascular disease. [Participants and Methods] The Short Physical Performance Battery, 6-minute walk distance, and functional independence measure tests were conducted in 79 inpatients with subacute cardiovascular disease (mean age, 76.7 ± 11.9 years; 34 females). Multiple regression analysis used the functional independence measure score as the dependent variable and the Short Physical Performance Battery and 6-minute walk distance scores as independent variables. Cross-tabulations were performed for each age group, and patients who performed the Short Physical Performance Battery and 6-minute walk distance tests were divided into two groups by their respective cutoff values. [Results] Only the Short Physical Performance Battery (β=0.568) and 6-minute walk distance (β=0.479) scores were adopted as significant independent variables in each multiple regression model. The age75 years group had the most patients with both good lower extremity function and aerobic capacity, whereas the age ≥75 years group had the most patients with both functions impaired. [Conclusion] Although cardiovascular disease is generally associated with decreased aerobic capacity, many older patients with cardiovascular disease in this study had decreased lower extremity function, too.

INTRODUCTION We tested our hypothesis that atrial entrainment pacing (EP) of a) the common-type (com-) fast-slow (F/S-) atypical atrioventricular nodal reentrant tachycardia (AVNRT) using a typical slow pathway (SP), or b) the superior-type (sup-) F/S-AVNRT using a superior SP, both modify the retrograde conduction time across the SP immediately after termination of EP (retro-SP-time). METHODS We measured the difference in the His-atrial interval (HA difference) immediately after cessation of EP, performed at 2 ± 2 rates from the high right atrium (HA[1]-HRA) versus from the proximal coronary sinus (HA[1]-CS) in 17 patients with com-F/S-AVNRT and 11 patients with sup-F/S-AVNRT. We also measured the atrial-His and HA intervals of the first and second cycles immediately after cessation of EP and during stable tachycardia. RESULTS Unequal responses, defined as a ≥ 20-ms HA difference at ≥1 EP rates, were observed in 16 patients (57%), including 7 with com- and 9 with sup-F/S-AVNRT. Irrespective of the EP rate, all unequal responses of com-F/S-AVNRT were due to a shorter HA[1]-CS than HA[1]-HRA, with a mean 34 ± 11 ms HA difference, whereas all unequal responses of sup-F/S-AVNRT were due to a longer HA[1]-CS than HA[1]-HRA, with a mean 49 ± 25 ms HA difference. The unequal responses resolved within two cycles after the cessation of EP. CONCLUSIONS We have identified a little-known pacing site- and pacing rate-dependent shortening of the retro-SP-time.

Balance impairment occurs after a hip fracture, but the characteristics of the impairment are not clear.To investigate the uni-dimensionality, fit statistics, and item difficulty of the Berg Balance Scale (BBS) in older adults with hip fracture by conducting a Rasch analysis.This was an observational cross-sectional study. The 254 participants were all ≥ 65 years old and had been hospitalized for rehabilitation after a unilateral hip fracture incurred during a fall. We collected their BBS scores at the time of hospital discharge and conducted a Rasch analysis to examine the uni-dimensionality, fit statistics, and item difficulty.The principal component analysis (PCA) of the Rasch model demonstrated that the BBS is uni-dimensional. The information-weighted mean square (MnSq) fit statistic was within the range of fit criteria for all items. The underfit item of the outlier-sensitive MnSq fit statistics was "Standing unsupported eyes closed" with the MnSq of 2.06. The difficult items were in order of logits: "Standing on one leg" (logits = 4.01); "Step tool" (logits = 2.74); and "Turn 360°" (logits = 2.61).The BBS is uni-dimensional and conforms with the Rasch model. The BBS most difficult items for older adults with a hip fracture required one-legged support and dynamic balance.

Balance dysfunction is common in stroke patients. The Berg Balance Scale (BBS) is useful for evaluating the balance function of stroke patients, and it can estimate the minimal clinically important difference (MCID) in balance. BBS scores differ among stroke patients depending on whether they require walking assistance. The MCID should thus be estimated separately for patients who require assistance and those who do not.To estimate the MCID of individuals who have had an early subacute stroke and require a walking aid and those who do not, to assist the clinical determination of the effectiveness of therapy.This was a retrospective clinical analysis of 80 early subacute stroke patients. We estimated the MCID by using the Functional Ambulation Categories (FAC) as anchors for changes in BBS scores during a 1-month period. The MCID was estimated based on a cutoff score for separating the patients who achieved a FAC change ≥1 point on receiver operator characteristic curves. The area under the curve (AUC) was used to measure the discrimination accuracy. The MCID was estimated for the patients who needed walking assistance and those who did not.The estimated MCID of BBS scores in the assisted-walking group was 5 points and the AUC was 0.84 (For early subacute stroke patients who require assistance to walk, a 5-point improvement in the BBS score is a useful indicator for reducing the amount of assistance.

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.This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients18 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.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.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.

This study sought to assess the performance of current diagnostic criteria and identify additional electrophysiological features differentiating orthodromic reciprocating tachycardia (ORT) with a concealed nodoventricular/nodofascicular (NV/NF) pathway from atrioventricular nodal re-entrant tachycardia (AVNRT).Diagnosing sustained supraventricular tachycardia (SVT) despite the occurrence of ventriculoatrial block (VAB) is challenging.We analyzed electrograms of 25 sustained SVTs (9 NV/NF-ORTs [n = 7/2] and 16 AVNRTs) with VAB and 91 AVNRTs without VAB (for reference).More than 1 SVT, each with a different ventriculoatrial interval, was commonly induced in AVNRT cases (75%) but not in NV/NF-ORT cases (0%; p = 0.0005). Wenckebach VAB was common in NV/NF-ORTs (78%), but VAB patterns varied in AVNRTs. The His-His interval transiently prolonged in the following beat after the VAB in most AVNRTs but rarely did in NV/NF-ORTs (79% vs. 22%; p = 0.01). NV/NF-ORT was diagnosed by His-refractory premature ventricular contractions (n = 5) and the findings during right ventricular overdrive pacing showing an uncorrected/corrected post-pacing interval (PPI)-tachycardia cycle length (TCL) ≤115/110 ms (n = 5/5), orthodromic His capture (n = 6), and V-V-A (ventricle-ventricle-atrial response) response (n = 3). A single form of induced SVT (positive predictive value [PPV]: 69%; negative predictive value [NPV]: 100%), Wenckebach VAB (PPV: 70%; NPV: 87%), stable His-His interval despite VAB (PPV: 70%; NPV: 85%), orthodromic His capture (PPV: 100%; NPV: 97%), and V-V-A response (PPV: 100%; NPV: 95%) characterized NV/NF-ORT, and a PPI-TCL of ≤125 ms (PPV: 100%; NPV: 100%) characterized NV-ORT.Induction of a single SVT form, Wenckebach VAB, stable His-His interval despite VAB, orthodromic His capture, and V-V-A response appeared to discriminate NV/NF-ORT from AVNRT, with a PPI-TCL of ≤125 ms discriminating NV-ORT from NF-ORT and AVNRT.

[Purpose] To present an accurate and straight-forward system of fall prediction by performing decision tree analysis using both the fall assessment sheet and Berg balance scale (BBS). [Participants and Methods] The participants in this retrospective study were inpatients from acute care units. We extracted the risk factors for falls from the fall assessment and performed a decision tree analysis using the extracted fall risk factors and BBS score. [Results] "History of more than one fall in the last 1 year", "Muscle weakness", "Use of a walking aid or wheelchair", "Requires assistance for transfer", "Use of Narcotics", "Dangerous behavior", and "High degree of self-reliance" were fall risk factors. The decision tree analysis extracted five fall risk factors, with an area under the curve of 0.7919. Patients with no history of falls and who did not require assistance for transfer or those with a BBS score ≥51 did not fall. [Conclusion] Decision tree-based fall prediction was useful and straightforward and revealed that patients with no history of falling and those who did not require assistance for transfer or had a BBS score ≥51 had a low risk of falling.

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.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.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.ΔAA is a useful, confirmatory, diagnostic indicator of F/S-AVNRT versus AT associated with the V-A-A-V response.

The aim of the current study was to identify a cut-off value for predicting walking independence at discharge in older adults with hip fracture based on their Berg Balance Scale (BBS) score at admission to a convalescent rehabilitation ward.This was a retrospective, multicenter, observational study of 187 older adults with hip fractures (mean age 83.7, range 66-97 years). Data was collected on the patients' age, sex, treatment, and physical function evaluation. An ordinal logistic regression analysis was used to identify predictors associated with the degree of independence in walking at discharge. Receiver operating characteristic curves were used to estimate cut-off values to predict independent and supervised walking at discharge based on the BBS score at admission. The accuracy of the classification was assessed using the area under the curve (AUC).The BBS score at admission was a significant factor predicting the degree of walking independence at discharge (odds ratio = 1.09, 95%CI: 1.06-1.11). The cut-off values of the BBS score at admission for predicting independent walking and supervised walking at discharge were 28 points (AUC = 0.76, 95%CI: 0.69-0.83) and 21 points (AUC = 0.84, 95%CI: 0.77-0.91), respectively.The BBS scores of older adults with hip fracture on admission to a rehabilitation ward are useful for predicting the degree of independence in walking at discharge and can help to structure therapy according to the predicted degree of independence.

To identify the Berg Balance Scale (BBS) values that can be used to discriminate the use of a walking aid and the BBS sub-items that reveal the differences in the use of walking aids among hospitalized older adults with a hip fracture.The cases of 77 older adults (age 80.8 ± 7.5 years) with a hip fracture who were able to walk independently in the hospital were retrospectively analyzed. A receiver operating characteristic curve (AUC) analysis was used to identify BBS scores that optimized the identification of subjects with different levels of aids. The BBS sub-items identifying differing among the walking aids were identified by a classification and regression tree analysis.The BBS scores were highest for no aid, a cane, and a walker, in that order. The ability to walk without an aid and the ability to walk without a walker showed moderate AUCs (0.824 and 0.865) with cutoff values of 51.5 and 45.5 points, respectively. The sub-items identified were Turning 360° (4 vs.4 points) as the best discriminator for using/not using a cane and Stool Stepping (≥ 2 vs.2 points) for using a cane or walker.The BBS is useful for determining whether to discontinue the use of a walker in individuals with a hip fracture.

While a KCND3 V392I mutation uniquely displays a mixed electrophysiological phenotype of Kv4.3, only limited clinical information on the mutation carriers is available. We report two teenage siblings exhibiting both cardiac (early repolarization syndrome and paroxysmal atrial fibrillation) and cerebral phenotypes (epilepsy and intellectual disability), in whom we identified the KCND3 V392I mutation. We propose a link between the KCND3 mutation with a mixed electrophysiological phenotype and cardiocerebral phenotypes, which may be defined as a novel cardiocerebral channelopathy.

BACKGROUND The epinephrine infusion test (EIT) typically induces marked QT prolongation in LQT1, but not LQT3, while the efficacy of β-blocker therapy is established in LQT1, but not LQT3. We encountered an LQT3 family, with an SCN5A V1667I mutation, that exhibited epinephrine-induced marked QT prolongation. METHODS Wild-type (WT) or V1667I-SCN5A was transiently expressed into tsA-201 cells, and whole-cell sodium currents (INa ) were recorded using patch-clamp techniques. To mimic the effects of epinephrine, INa was recorded after the application of protein kinase A (PKA) activator, 8-CPT-cAMP (200 μM), for 10 minutes. RESULTS The peak density of V1667I-INa was significantly larger than WT-INa (WT: 469 ± 48 pA/pF, n = 20; V1667I: 690 ± 62 pA/pF, n = 19, P

We report a case of atypical slow-slow atrioventricular nodal reentrant tachycardia (AVNRT) utilizing a superior slow pathway as a retrograde limb. The standard electrophysiological criteria confirm the diagnosis of this AVNRT by successfully excluding a diagnosis of atrial tachycardia and atrioventricular reentrant tachycardia. The earliest atrial activation during tachycardia was found at the interatrial septum 17.5 mm superior to the site identified during retrograde conduction with the fast pathway. The tachycardia was not inducible after ablation at the right posterior septum, consistent with successful ablation of the typical slow pathway.

Introduction: The entrainment rule by which the site of entrainment has no effect on the orthodromic conduction time across the reentry circuit immediately after cessation of pacing has not been unequivocally verified in atypical atrioventricular nodal reentrant tachycardia (AVNRT). We have recently observed a unique electrophysiological response upon atrial induction of fast-slow (F/S-) AVNRT, characterized by a shortening of the retrograde conduction time across the slow pathway (SP) (retro-SP-time). Hypothesis: Atrial entrainment pacing (EP) of a) the common-type (com-) F/S-AVNRT using a typical SP, or b) the superior-type (sup-) F/S-AVNRT using a superior SP, both might modify the retro-SP-time immediately after termination of EP. Methods: In 16 patients of com-F/S-AVNRT and 11 patients of sup-F/S-AVNRT in whom successful EP from the high right atrium (EP-HRA) and the proximal coronary sinus (EP-CS) was obtained at 2±2 rates, we evaluated the difference in the His-atrial (HA) interval measured immediately after cessation of each EP attempt (HA difference) between EP-HRA and EP-CS (HA[1]-HRA and HA[1]-CS, respectively) and also measured atrial-His and HA intervals in the 1st and 2nd cycles immediately after the EP, and during tachycardia stabilized. Results: >20 ms HA difference, defined as an atypical difference, at ≥1 rates of EP was observed in 16 patients (56%), including 7 with com- and 9 with sup-F/S-AVNRT. Irrespective of the EP rate, the atypical response of com-F/S-AVNRT was always due to a shorter HA[1]-CS than HA[1]-HRA, with a 39±22 ms HA difference, whereas the atypical response of sup-F/S-AVNRT was always due to a longer HA[1]-CS than HA[1]-HRA, with a 51±26 ms HA difference. Moreover, the atypical response disappeared within 2 cycles after the cessation of EP. The atypical difference, although its exact mechanism remains unclear, might attribute to a shortening of the retro-SP-time according to decremental properties of the SP with deeper antidromic penetration during EP provoked depending on the site and rate of pacing. Conclusions: We have identified a little-known pacing site- and pacing rate-dependent shortening of the retro-SP-time. This phenomenon may affect an interpretation of post-pacing interval after EP of F/S-AVNRT.

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)Ⅰ-Ⅱ 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 DⅠ-Ⅱ 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 DⅠ-Ⅱ 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%, PCa 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, PBa 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 DⅠ-Ⅱ linker in phenotypic manifestations.

Background Fast-slow (F/S-) atrioventricular (AV) nodal reentrant tachycardia (AVNRT) is characterized by a short atrio-His (AH) interval and the earliest site of atrial activation (EAA) in the proximal coronary sinus (EAA-CS), while slow-slow (S/S-) AVNRT presents a long AH interval and EAA-CS. Those intracardiac appearances are initial indicators for making a diagnosis. Purpose To identify an unknown phenotype of F/S-AVNRT. Methods Among 46 consecutive patients with F/S-AVNRT, 6 patients (1 man, age 59±9) had an apparent but not typical (pseudo-) S/S-AVNRT during an electrophysiologic study. In 2 patients, pseudo-S/S-AVNRT was clinically documented. Results In all 6 patients, the diagnosis of F/S-AVNRT was made by an exclusion of atrial tachycardia with findings of 1) a V-A-V response following ventricular entrainment or 2) termination without atrial capture by ventricular pacing, and an exclusion of AV reentrant tachycardia with a ventriculoatrial dissociation during an initial (so-called QRS transition) zone of ventricular entrainment. An initial A-A-V activation sequence on atrial induction of F/S-AVNRT observed in 1 patient and Wenckebach-type AV block during ongoing F/S-AVNRT developing in 3 patients suggested the presence of the lower common pathway (LCP). Like the typical S/S-AVNRT, pseudo-S/S-AVNRT was induced with atrial stimulation after a jump in the AH interval or double ventricular response. However, in all patients, the pseudo-S/S-AVNRT transited to F/S-AVNRT following AV block in a single cycle and/or pseudo-S/S-AVNRT transited from spontaneously or triggered by atrial contractions. Importantly, on these transitions, the atrial cycle length (CL) and EAA-CS remained unchanged, that is, the atrial CL of S/S-AVNRT was almost identical to that of F/S-AVNRT, suggesting that the essential circuit of both tachycardias was identical. Actually, both tachycardias were cured by ablation at a single site in the traditional slow pathway (SP). Collectively, the pseudo-S/S-AVNRT was diagnosed as another phenotype of F/S-AVNRT accompanied by sustained antegrade conduction via another bystander (likely the left-sided or superior) SP breaking through the His bundle owing to the repetitive antegrade block at the LCP occurring by linking phenomenon, thus representing a long AH interval during the ongoing F/S-AVNRT. When the antegrade conduction is blocked at the bystander SP during the pseudo-S/S-AVNRT, releasing the linking phenomenon, the subsequent antegrade conduction reach the His-bundle via the fast pathway, thus returning to F/S-AVNRT. Conclusions An unknown, but not rare F/S-AVNRT phenotype exists that apparently mimics the typical S/S-AVNRT and is also an unknown subtype of apparent S/S-AVNRT. The presence of this pseudo-S/S-AVNRT suggests the limitation of classifying types of AVNRT based on AH and HA intervals during tachycardia. Understandings of this phenotype can advance a diagnosis of atypical AVNRT with multiple phenotypes. Funding Acknowledgement Type of funding sources: None.

Purpose The minimal clinically important difference (MCID) is the smallest clinically significant difference in treatment identified as crucial to the patient. There is no known MCID for the Berg Balance Scale (BBS), which measures balance function in patients with hip fractures. We aimed to calculate the MCID of the BBS in older adults with hip fractures. Materials and methods This is a retrospective multicenter clinical study that included 187 older adults with hip fractures. MCID was calculated using functional ambulation categories (FACs), which were used as anchors for the change in BBS scores between admission and discharge. MCID was calculated as an improvement for more than one point and as a substantial change for improvement for more than two points in the FAC. Results MCID of the BBS was 11.5 points and that of the substantial change was 18.5 points, with an area under the curve of 0.76 and 0.81, respectively. Conclusions MCID for the BBS was 11.5 points in older adults with hip fractures. In addition, an improvement of more than 18.5 points in BBS can be considered a substantial change. These values may be useful in determining meaningful balance function improvement.Implications for rehabilitationHip fractures are a common injury for the older adults, and improvement in gait function has a bearing on prognosis.The effectiveness of meaningful rehabilitation is possible to determine by clarifying the minimal clinically important difference in balance function, which is important for the acquisition of gait.An improvement of 11.5 points or more on the Berg Balance Scale in an older adult with a hip fracture is considered a meaningful effect.

We report a case of atypical fast-slow atrioventricular nodal reentrant tachycardia (AVNRT) using a slow pathway variant extending to the superoanterior right atrium. The AVNRT diagnosis was confirmed by using standard electrophysiological criteria that exclude a diagnosis of atrial tachycardia and atrioventricular reentrant tachycardia. The earliest atrial activation during tachycardia was found in the superoanterior right atrium adjacent to the tricuspid annulus, where the first delivery of radiofrequency energy terminated and eliminated the inducibility of the tachycardia.

Most causal genes for inherited arrhythmia syndromes (IASs) encode cardiac ion channel-related proteins. Genotype-phenotype studies and functional analyses of mutant genes, using heterologous expression systems and animal models, have revealed the pathophysiology of IASs and enabled, in part, the establishment of causal gene-specific precision medicine. Additionally, the utilization of induced pluripotent stem cell (iPSC) technology have provided further insights into the pathophysiology of IASs and novel promising therapeutic strategies, especially in long QT syndrome. It is now known that there are atypical clinical phenotypes of IASs associated with specific mutations that have unique electrophysiological properties, which raises a possibility of mutation-specific precision medicine. In particular, patients with Brugada syndrome harboring an SCN5A R1632C mutation exhibit exercise-induced cardiac events, which may be caused by a marked activity-dependent loss of R1632C-Nav1.5 availability due to a marked delay of recovery from inactivation. This suggests that the use of isoproterenol should be avoided. Conversely, the efficacy of β-blocker needs to be examined. Patients harboring a KCND3 V392I mutation exhibit both cardiac (early repolarization syndrome and paroxysmal atrial fibrillation) and cerebral (epilepsy) phenotypes, which may be associated with a unique mixed electrophysiological property of V392I-Kv4.3. Since the epileptic phenotype appears to manifest prior to cardiac events in this mutation carrier, identifying KCND3 mutations in patients with epilepsy and providing optimal therapy will help prevent sudden unexpected death in epilepsy. Further studies using the iPSC technology may provide novel insights into the pathophysiology of atypical clinical phenotypes of IASs and the development of mutation-specific precision medicine.

Background: The existence of atypical fast-slow (F/S) atrioventricular (AV) nodal reentrant tachycardias (NRT) using slow pathway (SP) variants connected to the right atrial (RA) inferolateral (inf) free wall (FW) along the tricuspid annulus (TA), has been neither confirmed nor precisely characterized. Methods and Results: We studied 7 patients (mean age, 48±16 years; 5 men) with F/S-AVNRT with long RP intervals and an earliest atrial activation at the RA inf-FW along the TA (inf-F/S-AVNRT). AV reentrant tachycardia was excluded on observation of the transition zone criteria in all 7 patients. Atrial tachycardia was excluded on the observation of a V-A-V activation sequence after the induction or entrainment of the tachycardia from the right ventricle in all. During the tachycardia, low-frequency, fractionated potentials (LP) preceding the local atrial electrogram were recorded near the site of the earliest atrial activation in 6 patients. Observations of conduction delay and block of the LP during ventricular entrainment or ablation of the tachycardia indicated that LP reflect retrograde activation via the inf-SP. Retrograde SP conduction was interrupted at the site of earliest atrial activation in 3 patients, and in the right posterior septum in 4 patients. Conclusions: inf-F/S-AVNRT are distinct supraventricular tachycardia incorporating an SP variant connected to the RA inf-FW along the TA in the retrograde direction, which were eliminated by ablation.

Background SCN5A mutations are associated with multiple arrhythmic and cardiomyopathic phenotypes including Brugada syndrome (BrS), sinus node dysfunction (SND), atrioventricular block, supraventricular tachyarrhythmias (SVTs), long QT syndrome (LQTS), dilated cardiomyopathy and left ventricular noncompaction. Several single SCN5A mutations have been associated with overlap of some of these phenotypes, but never with overlap of all the phenotypes. Objective We encountered two pedigrees with multiple arrhythmic phenotypes with or without cardiomyopathic phenotypes, and sought to identify a responsible mutation and reveal its functional abnormalities. Methods Target panel sequencing of 72 genes, including inherited arrhythmia syndromes- and cardiomyopathies-related genes, was employed in two probands. Cascade screening was performed by Saner sequencing. Wild-type or identified mutant SCN5A were expressed in tsA201 cells, and whole-cell sodium currents (INa) were recorded using patch-clamp techniques. Results We identified an SCN5A A735E mutation in these probands, but did not identify any other mutations. All eight mutation carriers exhibited at least one of the arrhythmic phenotypes. Two patients exhibited multiple arrhythmic phenotypes: one (15-year-old girl) exhibited BrS, SND, and exercise and epinephrine-induced QT prolongation, the other (4-year-old boy) exhibited BrS, SND, and SVTs. Another one (30-year-old male) exhibited all arrhythmic and cardiomyopathic phenotypes, except for LQTS. One male suddenly died at age 22. Functional analysis revealed that the mutant did not produce functional INa. Conclusions A non-functional SCN5A A735E mutation could be associated with multiple arrhythmic and cardiomyopathic phenotypes, although there remains a possibility that other unidentified factors may be involved in the phenotypic variability of the mutation carriers.

Background: Superior-type fast-slow (sup-F/S-) atrioventricular nodal reentrant tachycardia (AVNRT) is a rare AVNRT variant using a superior slow pathway (SP) as the retrograde limb. Its intracardiac appearance, characterized by a short atrio-His (AH) interval and the earliest site of atrial activation in the His-bundle, is an initial indicator for making a diagnosis. Methods: Among 22 consecutive patients with sup-F/S-AVNRT, 3 (age, 68–81 years) patients had an apparent slow-fast (S/F-) AVNRT characterized by a long AH interval and the earliest site of atrial activation in or superior to the His-bundle region (tachy-long-AH). Results: The diagnosis of sup-F/S-AVNRT was based on the standard criteria in 2 patients and on the occurrence of Wenckebach-type atrioventricular block during tachycardia, which was attributable to a block at the lower common pathway (LCP) below the circuit of the AVNRT, detected owing to the lower common pathway potentials, in one patient. As with the typical S/F-AVNRT, tachy-long-AH was induced after a jump in the AH interval. In contrast to typical S/F-AVNRT, fluctuation in the ventriculoatrial interval was observed during the tachy-long-AH. Ventricular overdrive pacing was unable to entrain or terminate the tachy-long-AH. Moreover, the tachy-long-AH reciprocally transited to/from sup-F/S-AVNRT spontaneously or was triggered by ventricular contractions while the atrial cycle length and earliest site of atrial activation remained unchanged. Both tachycardias were cured by ablation at a single site in the right-side para-Hisian region of 2 patients and the noncoronary aortic cusp of one patient. Collectively, the essential circuit of both tachycardias was identical, and the tachy-long-AH was diagnosed as another phenotype of sup-F/S-AVNRT accompanied by sustained antegrade conduction via another bystander slow pathway breaking through the His-bundle owing to the repetitive antegrade block at the lower common pathway, thus representing a long AH interval during the ongoing sup-F/S-AVNRT. Conclusions: An unknown sup-F/S-AVNRT phenotype exists that apparently mimics the typical S/F-AVNRT and is also an unknown subtype of apparent S/F-AVNRT.

While a KCND3 V392I mutation uniquely displays a mixed electrophysiological phenotype of Kv4.3, only limited clinical information on the mutation carriers is available. We report two teenage siblings exhibiting both cardiac (early repolarization syndrome and paroxysmal atrial fibrillation) and cerebral phenotypes (epilepsy and intellectual disability), in whom we identified the KCND3 V392I mutation. We propose a link between the KCND3 mutation with a mixed electrophysiological phenotype and cardiocerebral phenotypes, which may be defined as a novel cardiocerebral channelopathy.

Background The atrial and ventricular response observed immediately after cessation of ventricular induction/entrainment pacing is commonly analyzed to discriminate atrial tachycardia from other supraventricular tachycardias during electrophysiologic studies. However, the response in fast–slow atrioventricular nodal reentrant tachycardia (F/S-AVNRT) remains poorly investigated. Objective The purpose of this study was to analyze the atrial and ventricular activation patterns after ventricular pacing in F/S-AVNRT. Methods We enrolled 28 patients with F/S-AVNRT incorporating a typical slow pathway (typ-F/S-AVNRT) and 9 patients with F/S-AVNRT incorporating a superior slow pathway (sup-F/S-AVNRT). Results The V-A-A-V response was observed in 14 patients (38%) with F/S-AVNRT, more commonly in patients with sup-F/S-AVNRT than in those with typ-F/S-AVNRT (89% vs 21%, P = .0003). The underlying mechanisms included (1) a double atrial response (DAR) in 13 patients; (2) an anterograde block at the lower common pathway once after ventricular pacing in 2 patients; and (3) a pseudo–A-A-V response in 2 patients. The DAR was characterized by a V-A-A-V interatrial interval that was 55 ± 60 ms shorter than the tachycardia cycle length, whereas the block at the lower common pathway or infrahisian block had a V-A-A-V interatrial interval that was almost equal to or longer than the tachycardia cycle length. Conclusion The V-A-A-V activation sequence immediately after ventricular induction/entrainment pacing is observed in patients with F/S-AVNRT, particularly in patients with sup-F/S-AVNRT, and is caused by multiple mechanisms, including a DAR, which is the major etiology.

BACKGROUND SCN5A variants can be associated with overlapping phenotypes such as Brugada syndrome (BrS), sinus node dysfunction and supraventricular tachyarrhythmias. Our genetic screening of SCN5A in 65 consecutive BrS probands revealed two patients with overlapping phenotypes: one carried an SCN5A R1632C (in domain IV-segment 4), which we have previously reported, the other carried a novel SCN5A N1541D (in domain IV-segment 1). OBJECTIVE We sought to reveal whether or not these variants are associated with the same biophysical defects. METHODS Wild-type (WT) or mutant SCN5A was expressed in tsA201-cells, and whole-cell sodium currents (hNav1.5/INa) were recorded using patch-clamp techniques. RESULTS The N1541D-INa density, when assessed from a holding potential of -150 mV, was not different from WT-INa as with R1632C-INa, indicating that SCN5A N1541D did not cause trafficking defects. The steady-state inactivation curve of N1541D-INa was markedly shifted to hyperpolarizing potentials in comparison to WT-INa (V1/2-WT: -82.3 ± 0.9 mV, n = 15; N1541D: -108.8 ± 1.6 mV, n = 26, P

Background— The existence of an atypical fast-slow (F/S) atrioventricular nodal reentrant tachycardia (AVNRT) including a superior (sup) pathway with slow conductive properties and an atrial exit near the His bundle has not been confirmed. Methods and Results— We studied 6 women and 2 men (age, 74±7 years) with sup-F/S-AVNRT who underwent successful radiofrequency ablation near the His bundle. Programmed ventricular stimulation induced retrograde conduction over a superior SP with an earliest atrial activation near the His bundle, a mean shortest spike-atrial interval of 378±119 milliseconds, and decremental properties in all patients. sup-F/S-AVNRT was characterized by a long-RP interval; a retrograde atrial activation sequence during tachycardia identical to that over a sup-SP during ventricular pacing; ventriculoatrial dissociation during ventricular overdrive pacing of the tachycardia in 5 patients or atrioventricular block occurring during tachycardia in 3 patients, excluding atrioventricular reentrant tachycardia; termination of the tachycardia by ATP; and a V-A-V activation sequence immediately after ventricular induction or entrainment of the tachycardia, including dual atrial responses in 2 patients. Elimination or modification of retrograde conduction over the sup-SP by ablation near the right perinodal region or from the noncoronary cusp of Valsalva eliminated and confirmed the diagnosis of AVNRT in 4 patients each. Conclusions— sup-F/S-AVNRT is a distinct supraventricular tachycardia, incorporating an SP located above the Koch triangle as the retrograde limb, that can be eliminated by radiofrequency ablation.

A 79-year-old man with a history of ventricular septal defect underwent catheter ablation of drug refractory paroxysmal atrial flutter (AFL). The 12-lead electrocardiogram during tachycardia showed a biphasic, predominantly positive flutter wave with an initial negative component in leads II, III, and aVF, and positive flutter waves in leads V1 through V6 (Fig. 1, A), consistent with typical counterclockwise (CCW) AFL [1]. A decapolar catheter was advanced with its ♯17 and ♯18 poles in the proximal coronary sinus (CS), and a deflectable duodecapolar Halo catheter was placed parallel to the tricuspid annulus (TA), across the inferior vena cava (IVC)-TA isthmus, with its tip at the CS ostium (Fig. 1, B and C). Although we did not perform contrast CS venography to confirm the location of the CS ostium, we believe that the CS ostium is located near the 5 o'clock position of the mitral annulus as estimated by the shape of the CS catheter projected in the left anterior oblique fluoroscopic view, consistent with the location of the ♯17 and ♯18 poles of the CS catheter. The atrial activation sequence along the TA during ongoing tachycardia, combined with entrainment pacing at the IVC-TA isthmus, and 10 o'clock and 2 o'clock positions of the TA with a pacing cycle length of 220 ms confirmed the diagnosis of typical CCW AFL. We did not perform entrainment pacing from the CS. During entrainment pacing from any site along the TA, all atrial deflections in CS recordings immediately after the last pacing stimulus were captured with the activation sequence similar to that during the AFL and a spikeatrial interval shorter than AFL cycle length, consistent with an orthodromic capture. A line of radiofrequency energy delivery blocked conduction across the IVC-TA isthmus, terminated AFL, and restored sinus rhythm. Differential pacing from the low septal and lateral right atrial (RA) region confirmed the successful creation of bidirectional isthmus block. It is noteworthy that, during ongoing AFL before ablation, (1) a latency of low RA conduction, consistent with conduction across the septal isthmus, was observed along the distal Halo catheter (Fig. 1, D), and (2) recording of atrial activation along the CS, instead of being proximal to distal, was centrifugal from CS poles 9 to 10 (Fig. 1, D). What is the underlying electrophysiological mechanism of atypical atrial activation during typical CCW AFL?

Background RYR2, encoding cardiac ryanodine receptor, is the major responsible gene for catecholaminergic polymorphic ventricular tachycardia (CPVT). Meanwhile, KCNJ2, encoding inward‐rectifier potassium channel (IK1), can be the responsible gene for atypical CPVT. We recently encountered a family with CPVT and sought to identify a responsible gene variant. Methods A targeted panel sequencing (TPS) was employed in the proband. Copy number variation (CNV) in RYR2 was identified by focusing on read numbers in the TPS and long‐range PCR. Cascade screening was conducted by a Sanger method and long‐range PCR. KCNJ2 wild‐type (WT) or an identified variant was expressed in COS‐1 cells, and whole‐cell currents (IK1) were recorded using patch‐clamp techniques. Results A 40‐year‐old female experienced cardiopulmonary arrest while cycling. Her ECG showed sinus bradycardia with prominent U‐waves (≥0.2 mV). She had left ventricular hypertrabeculation at apex. Exercise induced frequent polymorphic ventricular arrhythmias. Her sister died suddenly at age 35 while bouldering. Her father and paternal aunt, with prominent U‐waves, received permanent pacemaker due to sinus node dysfunction. The initial TPS and cascade screening identified a KCNJ2 E118D variant in all three symptomatic patients. However, after focusing on read numbers, we identified a novel exon3 deletion of RYR2 (RYR2‐exon3 deletion) in all of them. Functional analysis revealed that KCNJ2 E118D generated IK1 indistinguishable from KCNJ2 WT, even in the presence of catecholaminergic stimulation. Conclusions Focusing on the read numbers in the TPS enabled us to identify a novel CNV, RYR2‐exon3 deletion, which was associated with phenotypic features of this family.