Narrow QRS ectopy with concealed connections from a para-Hisian origin to the proximal left fascicles.

INTRODUCTION: Catheter ablation of ectopy originating from the vicinity of the His bundle can be challenging. METHODS AND RESULTS: We report a case of a 33-year-old man with narrow QRS ectopy with preferential conduction from a para-Hisian origin to the proximal left fascicles, which was successfully eliminated by radiofrequency ablation in the right coronary cusp, guided by ultrahigh-resolution mapping of the His bundle, bundle branch, and fascicular electrograms. CONCLUSION: Some narrow QRS ectopy may originate from the vicinity of the conduction system, instead of the "true" conduction system, and have concealed connections from its origin to the conduction system.

Prognostic Importance of B-Type Natriuretic Peptide Level in Patients Undergoing Catheter Ablation for Atrial Fibrillation.

BACKGROUND: This study assessed the prognostic importance of B-type natriuretic peptide (BNP) concentrations for clinical events after catheter ablation for atrial fibrillation (AF).Methods and Results: We enrolled 1,750 consecutive patients undergoing initial AF ablation whose baseline BNP data were available from a large-scale multicenter observational cohort (TRANQUILIZE-AF Registry). The prognostic impact of BNP concentration on clinical outcomes, including recurrent tachyarrhythmias and a composite of heart failure (HF) hospitalization or cardiac death, was evaluated. Median baseline BNP was 94.2 pg/mL. During a median follow-up of 2.4 years, low BNP (<38.3 pg/mL) was associated with lower rates of recurrent atrial tachyarrhythmias than BNP concentrations ≥38.3 pg/mL (19.9% vs. 30.6% at 3 years; P<0.001) and HF (0.8% vs. 5.3% at 3 years; P<0.001). Multivariable Cox regression analyses revealed that low BNP was independently associated with lower risks of arrhythmia recurrence (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.47-0.82; P<0.001) and HF (HR 0.17; 95% CI 0.04-0.71; P=0.002). The favorable impact of low BNP on arrhythmia recurrence was prominent in patients with paroxysmal, but not non-paroxysmal, AF, particularly among those with long-standing AF. CONCLUSIONS: Low BNP concentrations had a favorable impact on clinical outcomes after AF ablation. The heterogeneous impact of baseline BNP concentrations on arrhythmia recurrence for the subgroups of patients divided by AF type warrants future larger studies with longer follow-up periods.

Occurrence of right ventricular dysfunction immediately after pericardiocentesis.

The changes in cardiac function that occur after pericardiocentesis are unclear. An understanding of the effect of pericardiocentesis on right ventricular (RV) and left ventricular (LV) function is clinically important. This study was performed to assess RV and LV function with echocardiography before and after pericardiocentesis. In total, 19 consecutive patients who underwent pericardiocentesis for more than moderate pericardial effusion were prospectively enrolled from August 2015 to October 2017. Comprehensive transthoracic echocardiography was performed before, immediately after (within 3 h), and 1 day after pericardiocentesis to investigate the changes in RV and LV function. The mean age of all patients was 72.6 ± 12.2 years. No pericardiocentesis-related complications occurred during the procedure, but one patient died of right heart failure 8 h after pericardiocentesis. After pericardiocentesis, RV inflow and outflow diameters increased (p < 0.05 versus values before pericardiocentesis), and the parameters of RV function (tricuspid annular plane systolic excursion, tricuspid lateral annular systolic velocity, fractional area change, and RV free wall longitudinal strain) significantly decreased (p < 0.001 versus values before pericardiocentesis). These abnormal values or RV dysfunction remained 1 day after pericardiocentesis (p > 0.05 versus values immediately after pericardiocentesis). Conversely, no parameters of LV function changed after pericardiocentesis. Of 19 patients, 13 patients showed RV dysfunction immediately after pericardiocentesis and 6 patients did not. RV free wall longitudinal strain before pericardiocentesis in patients with post-procedural RV dysfunction was reduced compared to those without post-procedural RV dysfunction ( - 18.9 ± 3.6 versus - 28.4 ± 6.3%; p = 0.005). The area under the curve values for prediction of post-procedural RV dysfunction was 0.910 for RV free wall longitudinal strain. The occurrence of RV dysfunction after pericardiocentesis should be given more attention, and pre-procedural RV free wall longitudinal strain may be a predictor of post-procedural RV dysfunction.

Allele-specific ablation rescues electrophysiological abnormalities in a human iPS cell model of long-QT syndrome with a CALM2 mutation.

Calmodulin is a ubiquitous Ca2+ sensor molecule encoded by three distinct calmodulin genes, CALM1-3. Recently, mutations in CALM1-3 have been reported to be associated with severe early-onset long-QT syndrome (LQTS). However, the underlying mechanism through which heterozygous calmodulin mutations lead to severe LQTS remains unknown, particularly in human cardiomyocytes. We aimed to establish an LQTS disease model associated with a CALM2 mutation (LQT15) using human induced pluripotent stem cells (hiPSCs) and to assess mutant allele-specific ablation by genome editing for the treatment of LQT15. We generated LQT15-hiPSCs from a 12-year-old boy with LQTS carrying a CALM2-N98S mutation and differentiated these hiPSCs into cardiomyocytes (LQT15-hiPSC-CMs). Action potentials (APs) and L-type Ca2+ channel (LTCC) currents in hiPSC-CMs were analyzed by the patch-clamp technique and compared with those of healthy controls. Furthermore, we performed mutant allele-specific knockout using a CRISPR-Cas9 system and analyzed electrophysiological properties. Electrophysiological analyses revealed that LQT15-hiPSC-CMs exhibited significantly lower beating rates, prolonged AP durations, and impaired inactivation of LTCC currents compared with control cells, consistent with clinical phenotypes. Notably, ablation of the mutant allele rescued the electrophysiological abnormalities of LQT15-hiPSC-CMs, indicating that the mutant allele caused dominant-negative suppression of LTCC inactivation, resulting in prolonged AP duration. We successfully recapitulated the disease phenotypes of LQT15 and revealed that inactivation of LTCC currents was impaired in CALM2-N98S hiPSC model. Additionally, allele-specific ablation using the latest genome-editing technology provided important insights into a promising therapeutic approach for inherited cardiac diseases.

Very long-term follow-up data of non-ischemic idiopathic dilated cardiomyopathy after beta-blocker therapy: recurrence of left ventricular dysfunction and predictive value of 123I-metaiodobenzylguanidine scintigraphy.

The management of idiopathic dilated cardiomyopathy (DCM) is well established. However, a subset of patients do not have recovery from or have recurrences of left ventricular (LV) dysfunction despite receiving optimal medical therapy. There are limited long-term follow-up data about LV function and the predictive value of iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy, especially among the Japanese population. We retrospectively investigated 81 consecutive patients with DCM (mean LV ejection fraction (EF) 28 ± 7.5%) who had undergone 123I-MIBG scintigraphy before starting ß-blockers. According to chronological changes in LVEF, study patients were classified into three subgroups: sustained recovery group, recurrence group, and non-recovery group. The outcome measure was cardiac death. Mean age was 59 ± 11 years and median follow-up was 11.5 (5.8-15.0) years. Thirty-six patients had recovery, 11 had recurrences, and 34 did not have recovery. The sustained recovery group had the best cardiac death-free survival, followed by the recurrence and non-recovery groups. Prolonged time to initial recovery was associated with recurrence of LV dysfunction. Large LV end-diastolic diameter and reduced heart to mediastinum ratio were associated with poor prognosis. In conclusion, with ß-blocker therapy, 14% of patients showed recurrences of LV dysfunction. Thus, careful follow-up is needed, keeping in mind the possibility of recurrence, even if LVEF once improved, especially in patients whose time to initial recovery was long. 123I-MIBG scintigraphy provides clinicians with additional prognostic information.

Clinical Manifestations and Long-Term Mortality in Lamin A/C Mutation Carriers From a Japanese Multicenter Registry.

BACKGROUND: Mutation in the lamin A/C gene (LMNA) is associated with several cardiac phenotypes, such as cardiac conduction disorders (CCD), atrial arrhythmia (AA), malignant ventricular arrhythmia (MVA) and left ventricular dysfunction (LVD), leading to sudden cardiac death (SCD) and/or end-stage heart failure. We investigated how these phenotypes are associated with each other and which of them are most important for total mortality. Methods and Results: A multicenter registry included 110 LMNA mutation carriers (age, 43±15 years, male: 62%) from 60 families. After genetic diagnosis of LMNA mutation (missense: 27%, non-missense: 73%), patients or subjects were followed to evaluate the manifestations of their phenotypes and the risk of total mortality; 90 patients could be followed (median: 5 [0-35] years). Prevalence of the 4 clinical phenotypes was significantly increased during follow-up. Among these phenotypes, AA was significantly associated with MVA. CCD was significantly associated with LVD. LVD, meanwhile, was significantly associated with CCD and MVA. Male sex was significantly associated with MVA. Furthermore, during follow-up, 17 patients died: 12 end-stage heart failure, 4 SCD and 1 stroke. LVD was the only independent predictor for all-cause death (OR: 41.7, 95% CI: 4.1-422.3; P=0.0016). CONCLUSIONS: Several cardiac phenotypes were age-dependently increased in LMNA mutation carriers, suggesting that ICD or CRT-D could suppress SCD after middle age; however, LVD leading to end-stage heart failure was the only independent predictor for total mortality.

Development of a Patient-Derived Induced Pluripotent Stem Cell Model for the Investigation of SCN5A-D1275N-Related Cardiac Sodium Channelopathy.

BACKGROUND: TheSCN5Agene encodes the α subunit of the cardiac voltage-gated sodium channel, NaV1.5. The missense mutation, D1275N, has been associated with a range of unusual phenotypes associated with reduced NaV1.5 function, including cardiac conduction disease and dilated cardiomyopathy. Curiously, the reported biophysical properties ofSCN5A-D1275N channels vary with experimental system.Methods and Results:First, using a human embryonic kidney (HEK) 293 cell-based heterologous expression system, theSCN5A-D1275N channels showed similar maximum sodium conductance but a significantly depolarizing shift of activation gate (+10 mV) compared to wild type. Second, we generated human-induced pluripotent stem cells (hiPSCs) from a 24-year-old female who carried heterozygousSCN5A-D1275N and analyzed the differentiated cardiomyocytes (CMs). AlthoughSCN5Atranscript levels were equivalent between D1275N and control hiPSC-CMs, both the total amount of NaV1.5 and the membrane fractions were reduced approximately half in the D1275N cells, which were rescued by the proteasome inhibitor MG132 treatment. Electrophysiological assays revealed that maximum sodium conductance was reduced to approximately half of that in control hiPSC-CMs in the D1275N cells, and maximum upstroke velocity of action potential was lower in D1275N, which was consistent with the reduced protein level of NaV1.5. CONCLUSIONS: This study successfully demonstrated diminished sodium currents resulting from lower NaV1.5 protein levels, which is dependent on proteasomal degradation, using a hiPSC-based model forSCN5A-D1275N-related sodium channelopathy.

A potential pitfall of the modified 12 lead electrocardiogram (Mason-Likar modification) in catheter ablation of idiopathic ventricular arrhythmias originating from the outflow tract.

AIMS: The Mason-Likar modified electrocardiogram (ML-ECG) can be interchanged with standard 12 lead ECG electrode positions (standard ECG) without affecting the diagnostic interpretation during sinus rhythm, but the morphological differences during ventricular arrhythmias have not been sufficiently evaluated. This study aimed to elucidate the morphological changes in the ML-ECG precordial leads. METHODS AND RESULTS: In 53 consecutive patients with premature ventricular contractions predicted to originate from the outflow tract (OT-PVCs), the arrhythmias were analysed by those two ECG methods. The OT-PVC origin sites, which were predicted by currently published criteria with the respective ECG methods prior to catheter ablation, were compared with the successful ablation sites. Compared with the standard-ECG, S-waves in the ML-ECG became shallower in leads V1-4 (P < 0.05 in lead V1; P < 0.001 in leads V2-4), and pseudo-R-waves in lead V1 appeared in seven patients. The precordial leads transition zone shifted counter-clockwise in 18 patients in the ML-ECG. In leads I and aVL, the negative deflection amplitudes of the ML-ECG were greater than those of the standard ECG (P < 0.001), and polarity reversals in lead I appeared in 18 patients. The R-wave amplitudes in all ML-ECG inferior leads were greater than those in the standard-ECG leads (all for P < 0.001). Those changes had an effect on the diagnostic indexes for the localization, and the specificity of the criteria for the ML-ECG was poorer than that for the standard-ECG. CONCLUSION: Great differences were found between those two ECG methods. Predicting OT-PVC origins by diagnostic criteria with the ML-ECG might result in a misdiagnosis and inefficient ablation.

Novel automated atrial pacemapping technique based on intracardiac pattern matching to identify the location of ectopic atrial activity.

Atrial ectopy from the pulmonary veins and non-pulmonary vein foci can trigger atrial fibrillation. In addition, the elimination of atrial ectopy is important to prevent recurrence. The intracardiac pattern matching technique has been reported as a useful method to manually visualize the location of triggers regardless of their frequency. We combined the original intracardiac pattern matching method with the automapping setting of CARTO CONFIDENCE and discovered the automated atrial pacemapping technique. We report two cases in which this technique was used to eliminate the atrial triggers. This technique achieved a time reduction and high-resolution mapping.

Recurrent episodes of atrioventricular nodal reentrant tachycardia: Sites of ablation success, ablation endpoint, and primary culprits for recurrence.

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.

A case with occurrence of antidromic tachycardia after ablation of idiopathic left fascicular tachycardia: mechanism of left upper septal ventricular tachycardia.

A 36-year-old male presented with verapamil-sensitive narrow QRS tachycardia. The patient underwent the catheter ablation of common idiopathic left fascicular ventricular tachycardia (ILVT) 2 years ago. During narrow QRS tachycardia, the diastolic and presystolic potentials (P1 and P2) were recorded at the left septum. Activation sequences of P1 and P2 were opposite from those in common ILVT. Entrainment of P1 at the upper septum exhibited concealed fusion and S-QRS equal to P1-QRS. Radiofrequency current to P1 suppressed VT. Idiopathic left upper septal VT might be the antidromic macroreentry of the common form of ILVT.

Combined dominant frequency and complex fractionated atrial electrogram ablation after circumferential pulmonary vein isolation of atrial fibrillation.

INTRODUCTION: Atrial substrates with high-dominant frequency (DF) and complex fractionated atrial electrogram (CFAE) sites have sources maintaining atrial fibrillation (AF) and are potential AF ablation targets. This study aimed to evaluate an approach of circumferential pulmonary vein isolation (PVI) followed by a DF and CFAE site ablation. METHODS AND RESULTS: Fifty consecutive AF patients (23 paroxysmal, 9 persistent, and 18 longstanding persistent) underwent ablation, using NavX. When AF continued after circumferential PVI, high-DF sites of ≥ 8 Hz and then continuous left atrial (LA) CFAE sites defined by fractionated intervals (FI) of ≤50 milliseconds including the coronary sinus and right atrium were targeted. A total of 45.1% of high-DF and 48.1% of continuous CFAE sites significantly decreased after PVI (P < 0.001). The mean LA DF and FI significantly decreased and prolonged, respectively, after PVI (P < 0.001). Only 14.1% of all high-DF sites after PVI overlapped with continuous CFAE sites. AF terminated at high-DF sites in 11 (22%) patients and continuous CFAE sites in 1 (2%). AF could be induced in only 8% of patients after the procedure. The mean LA DF value before ablation was significantly lower in those without recurrence (P = 0.003). AF freedom on antiarrhythmic drugs was 96% and 59%, respectively, in the paroxysmal and nonparoxysmal AF patients (89% persistent and 44% longstanding persistent) after 1 procedure over a 12-month follow-up. CONCLUSIONS: A combined high-DF and continuous CFAE site ablation in all chambers after circumferential PVI may be effective in the paroxysmal and persistent AF patients.

Predictors of asymptomatic cerebral infarction associated with radiofrequency catheter ablation for atrial fibrillation using an irrigated-tip catheter.

AIMS: Catheter ablation is a potentially curative treatment for atrial fibrillation (AF). However, complications such as ischaemic stroke are more frequent and more severe compared with ablation procedures for other arrhythmias. Irrigated-tip catheters have been reported to reduce the risk of stroke. The present study aimed to evaluate predictors of asymptomatic cerebral infarction (CI) after AF ablation using an irrigated-tip catheter. METHODS AND RESULTS: A total of 70 consecutive AF patients who underwent catheter ablation were subjected to brain magnetic resonance imaging (MRI) 1 day after the procedure. In 10 (14.3%) of 70 patients, MRI revealed acute CI, but neither symptoms nor abnormal neurological findings were present in these patients. In univariate analysis, a history of persistent AF, left atrial dimension, presence of spontaneous echo contrast (SEC), procedure duration prior to heparin injection, and electrical cardioversion during the procedure differed significantly between the two groups, those with and without CI (P = 0.02, 0.05, 0.01, 0.01, and 0.05, respectively). Multivariate logistic regression analysis identified SEC [odds ratio (OR), 9.39; 1.60-55.2; P = 0.01] and procedure duration prior to heparin injection (OR, 1.19; 1.04-1.36; P = 0.01) as predictive of acute asymptomatic CI after AF ablation. CONCLUSION: The presence of SEC and procedure duration prior to heparin injection are determinants of asymptomatic CI during AF ablation despite the use of an irrigated-tip catheter.

The impact of home electrocardiograph measurement rate on the detection of atrial fibrillation recurrence after ablation: A prospective multicenter observational study.

Background: This multicenter prospective observational study examined the impact of additionally using a home electrocardiograph (ECG) to detect atrial fibrillation (AF) recurrence after ablation. Methods: Between May 2019 and December 2020, 128 patients undergoing ablation were enrolled in the study. After performing ablation, they were instructed to measure their ECGs at home using Complete (ECG paired with a blood pressure monitor; Omron Healthcare, Japan) every day and to visit the hospital every 3 months until after 12 months for 24-hour Holter ECG and 12-lead ECG as usual care (UC). Results: After ablation, 94 patients were followed up, and AF recurrence at 12 months was detected more commonly in adjudicators-interpreted Complete (31 [33 %]) than in UC (18 [9 %]) (hazard ratio 1.95, 95 % confidence interval [95 %CI] 1.35-2.81, P < 0.001). In patients with recurrent AF found via both modalities (n = 16), the time to first AF detection by Complete was 40.9 ± 73.9 days faster than that in UC (P = 0.04). Notably, when the adherence to Complete measurement was divided by 80 %, the add-on effect of Complete on the detection of recurrent AF in UC indicated the hazard ratio (HR) of 1.71 (95 %CI 0.92-3.18, P = 0.09) for the low adherence (<80 %) group, but it was significant for the high adherence (≥80 %) group, with HR of 2.19 (95 %CI 1.43-3.36, P < 0.001). Conclusions: Despite a shorter measurement time, Complete detected recurrent AF more frequently and faster compared with UC after AF ablation. A significant adherence-dependent difference of Complete was found in detecting AF recurrence.

Risk of Adverse Outcomes Associated With Cardiac Sarcoidosis Diagnostic Schemes.

BACKGROUND: Multiple cardiac sarcoidosis (CS) diagnostic schemes have been published. OBJECTIVES: This study aims to evaluate the association of different CS diagnostic schemes with adverse outcomes. The diagnostic schemes evaluated were 1993, 2006, and 2017 Japanese criteria and the 2014 Heart Rhythm Society criteria. METHODS: Data were collected from the Cardiac Sarcoidosis Consortium, an international registry of CS patients. Outcome events were any of the following: all-cause mortality, left ventricular assist device placement, heart transplantation, and appropriate implantable cardioverter-defibrillator therapy. Logistic regression analysis evaluated the association of outcomes with each CS diagnostic scheme. RESULTS: A total of 587 subjects met the following criteria: 1993 Japanese (n = 310, 52.8%), 2006 Japanese (n = 312, 53.2%), 2014 Heart Rhythm Society (n = 480, 81.8%), and 2017 Japanese (n = 112, 19.1%). Patients who met the 1993 criteria were more likely to experience an event than patients who did not (n = 109 of 310, 35.2% vs n = 59 of 277, 21.3%; OR: 2.00; 95% CI: 1.38-2.90; P < 0.001). Similarly, patients who met the 2006 criteria were more likely to have an event than patients who did not (n = 116 of 312, 37.2% vs n = 52 of 275, 18.9%; OR: 2.54; 95% CI: 1.74-3.71; P < 0.001). There was no statistically significant association between the occurrence of an event and whether a patient met the 2014 or the 2017 criteria (OR: 1.39; 95% CI: 0.85-2.27; P = 0.18 or OR: 1.51; 95% CI: 0.97-2.33; P = 0.067, respectively). CONCLUSIONS: CS patients who met the 1993 and the 2006 criteria had higher odds of adverse clinical outcomes. Future research is needed to prospectively evaluate existing diagnostic schemes and develop new risk models for this complex disease.

Efficacy and safety of periprocedural dabigatran in patients undergoing catheter ablation of atrial fibrillation.

BACKGROUND: Periprocedural anticoagulation using uninterrupted warfarin could reduce the risk of thromboembolic complications of atrial fibrillation (AF) ablation. Few studies, however, have evaluated the efficacy and safety of periprocedural dabigatran in AF ablation. METHODS AND RESULTS: A total of 211 consecutive patients who underwent AF ablation, including 110 patients who received 110mg dabigatran twice daily (group D) and 101 patients who received dose-adjusted warfarin (international normalized ratio, 2.0-3.0; group W), were evaluated. Dabigatran was discontinued on the morning of the procedure, and resumed on the next morning. Warfarin was continued throughout the procedure. During the procedure, heparin infusion was maintained to achieve an activated clotting time of >300s. Postprocedural cerebral magnetic resonance imaging (MRI) was performed in 60 patients (group D, n=31; group W, n=29). No periprocedural deaths or symptomatic thromboembolic complications were observed in either group. MRI indicated a silent cerebral infarction in 1 patient in each group. Five patients in group D and 11 in group W had minor bleeding (P=0.12). Cardiac tamponade occurred in 2 patients in group W, but in none in group D. Total bleeding complications occurred less frequently in group D (4.5%) than in group W (12.9%; P<0.05). CONCLUSIONS: Dabigatran at a dose of 110mg twice daily was safe for AF ablation in patients with a relatively low risk of thromboemboli, suggesting that it may become an alternative to warfarin in those patients.

Improvement in quality of life and cardiac function after catheter ablation for asymptomatic persistent atrial fibrillation.

BACKGROUND: Catheter ablation (CA) for atrial fibrillation (AF) is widely performed. However, the indication for CA in patients with asymptomatic persistent AF is still controversial. METHODS: Among 259 consecutive patients who were hospitalized for initial CA of AF, a total of 45 patients who had asymptomatic persistent AF were retrospectively analyzed. Quality of life (QOL) before and 1 year after CA was evaluated, and changes in the cardiac function over 5 years after CA were also examined. QOL was assessed using the AF QOL questionnaire (AFQLQ) developed by the Japanese Heart Rhythm Society. In addition, cardiac function was assessed by measuring the plasma B-type natriuretic peptide (BNP) level, left ventricular ejection fraction (LVEF), left atrial diameter (LAD) with transthoracic echocardiogram, and left atrial (LA) volume with computed tomography (CT). RESULTS: The AFQLQ significantly improved after CA in terms of "symptom frequency" and "activity limits and mental anxiety." The plasma BNP level, LVEF, and LAD significantly improved in the first 3 months after the first CA, with no significant changes thereafter (from 149.0 pg/dL [95% confidence intervals {CI}, 114.5-183.5 pg/dL] to 49.8 pg/dL [95% CI, 26.5-70.1], P < .0001; from 60.8% [95% CI, 58.1%-63.6%] to 65.0% [95% CI, 62.6-67.4], P = .001; and from 41.3 mm [95% CI, 39.7-42.9] to 36.8 [95% CI, 34.5-39.1 mm], P < .0001, respectively). LA volume revealed LA reverse remodeling after CA. CONCLUSION: Improvement in the QOL and cardiac function after CA of asymptomatic persistent AF was revealed. Asymptomatic persistent AF should be appropriately treated by CA.

Successful Transcatheter Aortic Valve Implantation in a Patient with Radiation-induced Aortic Stenosis for Mediastinal Hodgkin Lymphoma.

Aortic stenosis (AS), a late complication of thoracic radiation therapy for chest lesions, is often coincident with porcelain aorta or hostile thorax. We herein report a 59-year-old man with a history of mediastinal Hodgkin lymphoma treated with radiation therapy but later presenting with heart failure caused by severe AS. Severe calcification in the mediastinum and around the ascending aorta made it difficult to perform surgical aortic valve replacement. The patient therefore underwent transcatheter aortic valve implantation (TAVI). It is important to recognize radiation-induced AS early, now that TAVI is a well-established treatment required by increasing numbers of successfully treated cancer patients.

Impact of right ventricular function on development of significant tricuspid regurgitation in patients with chronic atrial fibrillation.

BACKGROUND: Chronic atrial fibrillation (AF) can cause significant tricuspid regurgitation (TR), which may result from tricuspid annulus and right atrial enlargement. However, the impact of right ventricular (RV) function on TR development remains unclear. METHODS: We retrospectively examined 175 consecutive patients with lone chronic AF (duration >1 year) without left ventricular dysfunction. TR severity was graded by the jet area and vena contracta, and moderate or severe TR were defined as significant TR. Patients were classified as significant TR (TR group) or without (NTR group) for comparison of clinical factors and transthoracic echocardiographic (TTE) parameters. To explore factors associated with TR development, we also compared previous TTE parameters among patients in TR group who showed no prior significant TR [TR-preTR(-)] and those in NTR group [NTR-preTR(-)]. RESULTS: The mean age was 78 years (61% men). Significant TR was observed in 61 patients (35%). Compared with NTR group, the TR group was older, and had longer AF duration and larger right-sided cardiac parameters on index TTE. At previous TTE, the TR-preTR(-) group showed a larger basal RV dimension index (26.8 vs. 22.4mm/m2), reduced RV free wall longitudinal strain (RVLS-FW) (-18.96 vs. -23.23), and lower tricuspid annular diameter change during a cardiac cycle (8.8% vs. 14.1%) than NTR-preTR(-) group. CONCLUSION: Significant TR was observed in 35% of patients with chronic AF. These patients showed enlarged RV, reduced RVLS-FW, and low tricuspid annular diameter changes before significant TR develops. RV dysfunction may be associated with TR development in chronic AF.

Propranolol Attenuates Late Sodium Current in a Long QT Syndrome Type 3-Human Induced Pluripotent Stem Cell Model.

BACKGROUND: Long QT syndrome type 3 (LQT3) is caused by gain-of-function mutations in the SCN5A gene, which encodes the α subunit of the cardiac voltage-gated sodium channel. LQT3 patients present bradycardia and lethal arrhythmias during rest or sleep. Further, the efficacy of ß-blockers, the drug used for their treatment, is uncertain. Recently, a large multicenter LQT3 cohort study demonstrated that ß-blocker therapy reduced the risk of life-threatening cardiac events in female patients; however, the detailed mechanism of action remains unclear. OBJECTIVES: This study aimed to establish LQT3-human induced pluripotent stem cells (hiPSCs) and to investigate the effect of propranolol in this model. METHOD: An hiPSCs cell line was established from peripheral blood mononuclear cells of a boy with LQT3 carrying the SCN5A-N1774D mutation. He had suffered from repetitive torsades de pointes (TdPs) with QT prolongation since birth (QTc 680 ms), which were effectively treated with propranolol, as it suppressed lethal arrhythmias. Furthermore, hiPSCs were differentiated into cardiomyocytes (CMs), on which electrophysiological functional assays were performed using the patch-clamp method. RESULTS: N1774D-hiPSC-CMs exhibited significantly prolonged action potential durations (APDs) in comparison to those of the control cells (N1774D: 440 ± 37 ms vs. control: 272 ± 22 ms; at 1 Hz pacing; p < 0.01). Furthermore, N1774D-hiPSC-CMs presented gain-of-function features: a hyperpolarized shift of steady-state activation and increased late sodium current compared to those of the control cells. 5 µM propranolol shortened APDs and inhibited late sodium current in N1774D-hiPSC-CMs, but did not significantly affect in the control cells. In addition, even in the presence of intrapipette guanosine diphosphate ßs (GDPßs), an inhibitor of G proteins, propranolol reduced late sodium current in N1774D cells. Therefore, these results suggested a unique inhibitory effect of propranolol on late sodium current unrelated to ß-adrenergic receptor block in N1774D-hiPSC-CMs. CONCLUSION: We successfully recapitulated the clinical phenotype of LQT3 using patient-derived hiPSC-CMs and determined that the mechanism, by which propranolol inhibited the late sodium current, was independent of ß-adrenergic receptor signaling pathway.