Intramural needle ablation or repeated standard ablation in patients referred for repeat ablation of scar-related ventricular tachycardia.

INTRODUCTION: When ventricular tachycardia (VT) recurs after standard RF ablation (sRFA) some patients benefit from repeat sRFA, whereas others warrant advanced methods such as intramural needle ablation (INA). Our objectives are to assess the utility of repeat sRFA and to clarify the benefit of INA when repeat sRFA fails in patients with VT due to structural heart disease. METHODS: In consecutive patients who were prospectively enrolled in a study for INA for recurrent sustained monomorphic VT despite sRFA, repeat sRFA was considered first. INA was performed during the same procedure if repeat sRFA failed or no targets for sRFA were identified. RESULTS: Of 85 patients enrolled, acute success with repeat sRFA was achieved in 30 patients (35%), and during the 6-month follow-up, 87% (20/23) were free of VT hospitalization, 78% were free of any VT, and 7 were lost to follow-up. INA was performed in 55 patients (65%) after sRFA failed, or no endocardial targets were found abolished or modified inducible VT in 35/55 patients (64%). During follow-up, 72% (39/54) were free of VT hospitalization, 41% were free of any VT, and 1 was lost to follow-up. Overall, 59 out of 77 (77%) patients were free of hospitalization and 52% were free of any VT. Septal-origin VTs were more likely to need INA, whereas RV and papillary muscle VTs were less likely to require INA. CONCLUSIONS: Repeat sRFA was beneficial in 23% (18/77) of patients with recurrent sustained VT who were referred for INA. The availability of INA increased favorable outcomes to 52%.

Safety of ventricular arrhythmia radiofrequency ablation with half-normal saline irrigation.

AIMS: Failure of radiofrequency (RF) ablation of ventricular arrhythmias is often due to inadequate lesion size. Irrigated RF ablation with half-normal saline (HNS) has the potential to increase lesion size and reduce sodium delivery to the patient if the same volume of RF irrigant were used for normal saline (NS) and HNS but could increase risks related to steam pops and lesion size. This study aims to assess periprocedural complications and acute ablation outcome of ventricular arrhythmias ablation with HNS. METHODS AND RESULTS: Prospective assessment of outcomes was performed in 1024 endocardial and/or epicardial RF ablation procedures in 935 consecutive patients (median age 64 years, 71.2% men, 73.4% cardiomyopathy, 47.2% sustained ventricular tachycardia). Half-normal saline was selected at the discretion of the treating physician. Radiofrequency ablation power was generally titrated to a ≤15â€…Ω impedance fall with intracardiac echocardiography monitoring. Half-normal saline was used in 900 (87.9%) and NS in 124 (12.1%) procedures. Any adverse event within 30 days occurred in 13.0% of patients treated with HNS RF ablation including 4 (0.4%) strokes/transient ischaemic attacks and 34 (3.8%) pericardial effusions requiring treatment (mostly related to epicardial access). Two steam pops with perforation required surgical repair (0.2%). Patients who received NS irrigation had less severe disease and arrhythmias. In multivariable models, adverse events and acute success of the procedure were not related to the type of irrigation. CONCLUSION: Half-normal saline irrigation RF ablation with power guided by impedance fall and intracardiac echocardiography has an acceptable rate of complications and acute ablation success while administering half of the saline load expected for NS irrigation.

Epicardial adipose tissue density predicts the presence of atrial fibrillation and its recurrence after catheter ablation: three-dimensional reconstructed image analysis.

Epicardial adipose tissue (EAT) induces inflammation in the atria and is associated with atrial fibrillation (AF). Several studies have examined the relationship between EAT volume (EAT-V) and density (EAT-D) and the presence of AF after catheter ablation. However, conclusions have been inconsistent. This study included 43 consecutive patients who underwent catheter ablation for AF and 30 control patients. EAT-V and EAT-D around the entire heart, entire atrium, left atrium (LA), and right atrium (RA) were measured in detail using reconstructed three-dimensional (3D) EAT images from dual-source computed tomography (CT). None of the measurements of EAT-V differed significantly between patients with AF and controls or between patients with recurrent AF and those without. On the other hand, all measurements of EAT-D were higher in patients with AF than in controls (entire atrium, p < 0.001; RA, p < 0.001; LA, p = 0.002). All EAT-D measurements were associated with the presence of AF. Among patients with AF who underwent ablation, all EAT-D measurements were higher in patients with recurrent AF than in those without. The difference was significant for EATRA-D (p = 0.032). All atrial EAT-D values predicted recurrent AF (EATRA-D: hazard ratio [HR], 1.208; 95% confidence interval [95% CI], 1.053-1.387; p = 0.007; EATLA-D: HR, 1.108; 95% CI 1.001-1.225; p = 0.047; EATatrial-D: HR, 1.174; 95% CI 1.040-1.325; p = 0.010). The most sensitive cutoffs for predicting recurrent AF were highly accurate for EATRA-D (area under the curve [AUC], 0.76; p < 0.01) and EATatrial-D (AUC = 0.75, p < 0.05), while the cutoff for EATLA-D had low accuracy (AUC, 0.65; p = 0.209). For predicting the presence of AF and recurrent AF after catheter ablation, 3D analysis of atrial EAT-D, rather than EAT-V, is useful.

Treatment with catheter ablation for patients with arrhythmia-induced cardiomyopathy caused by atrial fibrillation promises a good prognosis.

Clinical outcomes after catheter ablation in patients with reduced left ventricular (LV) ejection fraction (EF) and atrial fibrillation (AF) remain unclear. This study aimed to explore the clinical outcomes of patients with arrhythmia-induced cardiomyopathy (AIC) and the influence of pharmacological treatment on clinical outcomes in patients with AIC after the procedure. Ninety-six patients with AF with a reduced LVEF (LVEF < 50%, 66.7 ± 10.9 years; 72 males) underwent AF ablation. AIC was defined as patients whose LVEF recovered ≥ 50% after catheter ablation (n = 67) and patients whose LVEF remained reduced were defined as non-AIC (n = 29). During a median follow-up of 25 (13-40) months, Kaplan-Meier analysis demonstrated that patients with AIC were associated with less frequent cardiovascular death (p = 0.025) and hospitalization for worsening heart failure (p < 0.001) than those without AIC. Freedom from AF recurrence was similar between the two groups (p = 0.47). In multivariate analysis, the LV end-diastolic diameter (p = 0.0002) and the CHA2DS2-VASc scores (p = 0.0062) were independent predictors of AIC. Among the 67 patients with AIC, no significant differences in baseline characteristics, except for LV chamber size and cryoballoon use, were observed between patients with AIC with (n = 31) and without renin-angiotensin system (RAS) inhibitors (n = 36). In the Kaplan-Meier analysis, cardiovascular death, hospitalization for worsening heart failure, and AF recurrence after catheter ablation did not differ between patients treated with and without RAS inhibitors (all p > 0.05). Catheter ablation in patients with AIC due to AF is associated with a good post-procedural prognosis.IRB information The study was approved by the Research Ethics Committee of the University of Fukui (No. 20220151) and clinical trial registration (UMIN000050391).

Intracardiac thrombi fluttering like hair in the wind at VT ablation.

INTRODUCTION: Intracardiac echocardiography (ICE) reveals mobile thrombus on implantable electronic device leads in some patients undergoing electrophysiologic procedures. METHODS: ICE was performed in a patient undergoing ventricular tachycardia (VT) ablation. RESULTS: ICE showed extensive mobile thrombi on the implantable cardioverter defibrillator lead. Radiofrequency catheter ablation of VT from perimitral scar was safely performed via a retrograde aortic approach. After the procedure, chronic anticoagulation was initiated. CT-angiography of the chest 2 months later showed no pulmonary emboli. CONCLUSIONS: The significance of these thrombi, as related to chronic pulmonary embolization, warrants further study.

Non-missense variants of KCNH2 show better outcomes in type 2 long QT syndrome.

AIMS: More than one-third of type 2 long QT syndrome (LQT2) patients carry KCNH2 non-missense variants that can result in haploinsufficiency (HI), leading to mechanistic loss-of-function. However, their clinical phenotypes have not been fully investigated. The remaining two-thirds of patients harbour missense variants, and past studies uncovered that most of these variants cause trafficking deficiency, resulting in different functional changes: either HI or dominant-negative (DN) effects. In this study, we examined the impact of altered molecular mechanisms on clinical outcomes in LQT2 patients. METHODS AND RESULTS: We included 429 LQT2 patients (234 probands) carrying a rare KCNH2 variant from our patient cohort undergoing genetic testing. Non-missense variants showed shorter corrected QT (QTc) and less arrhythmic events (AEs) than missense variants. We found that 40% of missense variants in this study were previously reported as HI or DN. Non-missense and HI-groups had similar phenotypes, while both exhibited shorter QTc and less AEs than the DN-group. Based on previous work, we predicted the functional change of the unreported variants-whether they cause HI or DN via altered functional domains-and stratified them as predicted HI (pHI)- or pDN-group. The pHI-group including non-missense variants exhibited milder phenotypes compared to the pDN-group. Multivariable Cox model showed that the functional change was an independent risk of AEs (P = 0.005). CONCLUSION: Stratification based on molecular biological studies enables us to better predict clinical outcomes in the patients with LQT2.

Contrast-enhanced computed tomography in the venous rather than the arterial phase is essential for the evaluation of the right phrenic nerve.

BACKGROUND: Preprocedural detection of the running course of the right pericardiophrenic bundles (PBs) is considered to be useful in preventing phrenic nerve (PN) injury during catheter ablation for atrial fibrillation (AF). However, previous studies using the arterial phase of contrast-enhanced computed tomography (CT) reported a relatively low right PBs detection rate. METHODS: This study included 63 patients with AF who underwent catheter ablation and preoperative contrast-enhanced CT imaging of the venous and arterial phases (66.7 ± 10.2 years; 44 male). The venous phase of contrast-enhanced CT significantly improved the detection rate of PBs compared to the arterial phase (96.8% vs. 60.3%, p < .001), and PBs were detected in the venous phase only in 23 (36.7%) patients. No significant differences were observed between the right PBs detection rate using non-contrast CT versus the arterial phase of contrast-enhanced CT (p = .37). Patients without visualization of the right PBs during the arterial phase had a higher frequency of chronic heart failure (p = .0083), lower left ventricular ejection fraction (p = .021), and a higher CHADS2 score (p = .048) than those with visualization. In five patients whose right PBs could only be detected during the venous phase of contrast-enhanced CT, the reconstructed running course of the right PBs corresponded with the PN generated by electrical high-output pacing. CONCLUSION: Contrast-enhanced CT images of the venous phase, rather than the arterial phase, are useful in detecting the right PBs, especially in patients with heart failure or reduced left ventricular ejection fraction.

The R Wave Amplitude in Lead aVL Could Predict Successful Catheter Ablation of Ventricular Arrhythmias Originating below the His Bundle Region of the Right Ventricle.

Radiofrequency catheter ablation (RFCA) to treat ventricular arrhythmias (VAs) originating below the His bundle (HB) region of the right ventricular (RV) septum could impair the atrioventricular node conduction. This study aimed to clarify the parameters of the 12-lead electrocardiography that predict successful RFCA of VAs originating from this region. This study included 20 consecutive patients (13 men; mean age, 68 ± 7 years) with monomorphic VAs in whom the earliest ventricular activation during the VA was below the HB region of the RV septum. According to the ablation results, the patients were divided into two groups: successful ablation (S-group; n = 10) and failed ablation groups (F-group; n = 10). The electrocardiographic parameters during the VAs and RFCA results were assessed. The R wave amplitudes in leads aVL (P = 0.001) and I (P = 0.010) in the S-group were both smaller than those in the F-group. In addition, the S-group had smaller negative deflection amplitudes in leads III (P = 0.002) and aVF (P = 0.003) than the F-group. According to the receiver operating characteristic curve analysis, the most useful electrocardiographic parameter for predicting successful ablation was the R wave amplitude in lead aVL (area under the curve, 0.895; P < 0.001); a cutoff value of < 1.3 mV predicted a successful RFCA with the highest accuracy (sensitivity, 90%; specificity, 80%; positive predictive value, 82%; negative predictive value, 89%). The R wave amplitude in lead aVL was the most useful parameter for predicting a successful RFCA to treat VAs originating below the HB region of the RV septum.

Safety and durability of cavo-tricuspid isthmus linear ablation in the current era: Single-center 9-year experience from 1078 procedures.

BACKGROUND: Cavo-tricuspid isthmus (CTI) linear ablation is performed not only for atrial flutter (AFL) but empirically during atrial fibrillation (AF) ablation in real-world practice.  PURPOSE: We sought to evaluate the safety and durability of the CTI ablation.  METHODS: This retrospective study included 1078 consecutive patients who underwent a CTI ablation. AFL was documented before or during the procedure in 249 (23.1%) patients, and an empirical CTI and AF ablation were performed in 829 (76.9%) patients.  RESULTS: CTI block was successfully created in 1051 (97.5%) patients with a 10.3 ± 6.6 min total radiofrequency time. Repeat procedures were performed for recurrent arrhythmias in 187 (17.3%) patients at a median of 11.0 (5.0-30.0) months postprocedure, and conduction resumption was identified in 68/174 (39.1%). Among those undergoing a CTI ablation with an AF ablation, the durability was significantly higher in those with than without documented AFL (78.1% vs. 58.2%, p = .031).  The total radiofrequency time was significantly shorter (9.0 ± 5.3 vs. 10.0 ± 6.4 [mins], p = .024) and durability significantly higher (78.1 vs. 58.7[%], p = .043) in the large-tip than irrigated-tip catheter group. Iatrogenic AFL was observed after the empiric CTI ablation in 11 (1.3%) patients. Procedure-related complications occurred in 15 (1.4%) patients. Eight patients experienced coronary artery spasms, including one with ventricular fibrillation following ST elevation on the ward. The other six patients experienced transient atrioventricular block and one experienced cardiac tamponade requiring drainage.  CONCLUSIONS: Despite a high acute CTI ablation success, the conduction block durability was relatively low after the empiric ablation. An empiric CTI ablation at the time of the AF ablation is not recommended.

Subclinical sinus node dysfunction in patients with atrial fibrillation-Insight from ultrahigh-resolution mapping of human sinoatrial exits.

BACKGROUND: Even a short duration of paroxysmal episodes of atrial fibrillation (AF) is associated with sinus node (SN) remodeling and a reduced SN reserve or dysfunction. The number of earliest atrial activation sites (EASs) during sinus rhythm decreases according to the decrease in the SN reserve. OBJECTIVE: We sought to evaluate the EASs during sinus rhythm using an ultrahigh-density mapping system. METHODS: This study included 35 patients (supraventricular tachycardia [SVT]/paroxysmal atrial fibrillation [PAF]/persistent atrial fibrillation [PsAF] = 5/21/9) who underwent ultrahigh-resolution endocardial mapping of the SN area at rest and during ß-stimulation. The number of EASs was determined by the Lumipoint™ algorithm. RESULTS: The number of EASs was greatest in SVT patients both at rest (SVT/PAF/PsAF = 1.4 ± 0.8/1.0 ± 0/1.0 ± 0, p = .04) and during ß-stimulation (SVT/PAF/PsAF = 2.6 ± 1.0/1.3 ± 0.6/1.0 ± 0, p < .01). The number significantly increased with ß-stimulation as compared to baseline in the PAF patients (p = .02), but not in the PsAF patients. The brain natriuretic peptide (BNP) level was significantly higher in AF than SVT patients (SVT/PAF/PsAF = 12.3 [10.1-14.5]/25.7 [14.8-36.0]/73.4 [57.6-140] pg/ml, p < .01). In the PAF patients, the BNP level was significantly higher in those with unicentric EASs than multicentric EASs during ß-stimulation (28.1 [19.1-46.5] vs. 13.1 [9.4-26.9] pg/ml, p = .03), and the optimal cutoff point for the BNP level predicting unicentric EASs was 21.8 pg/ml (sensitivity 82.6%; specificity 85.7%). CONCLUSIONS: AF patients have a smaller number of EASs and poorer response to ß-stimulation than non-AF patients. An elevated BNP level might predict subclinical SN dysfunction in patients with PAF.

Mapping and ablation of left atrial roof-dependent tachycardias using an ultra-high resolution mapping system.

BACKGROUND: Left atrial roof-dependent tachycardias (LARTs) are common macroreentrant atrial tachycardias (ATs). We sought to characterize clinical LARTs using an ultra-high resolution mapping system. METHODS: This study included 22 consecutive LARTs in 21 patients who underwent AT mapping/ablation using Rhythmia systems. RESULTS: Three, 13, 4, and 2 LART patients were cardiac intervention naïve (Group-A), post-roof line ablation (Group-B), post-atrial fibrillation ablation without linear ablation (Group-C), and post-cardiac surgery (Group-D), respectively. The mean AT cycle length was 244 ± 43 ms. Coronary sinus activation was proximal-to-distal or distal-to-proximal in 16 (72.7%) ATs. The activation map revealed 13 (59.1%) clockwise and 9 (40.9%) counter-clockwise LARTs. A 12-lead synchronous isoelectric interval was observed in 10/19 (52.6%) LARTs. The slow conduction area was identified on the LA roof, anterior/septal wall, and posterior wall in 18, 6, and 2 ATs, respectively. Twenty concomitant ATs among 13 procedures were also eliminated, and peri-mitral AT coexisted in 7 of 9 non-group-B patients. In group-B, the conduction gap was predominantly located on the mid-roof. Sustained LARTs were terminated by a single application and linear ablation in 6 (27.3%) and 9 (40.9%), while converting to other ATs in 7 (31.8%) LARTs. Complete linear block was created without any complications in all, however, ablation at the mid-posterior wall was required to achieve block in 4 (18.2%) procedures. During 14.0 (6.5-28.5) months of follow-up, 17 (81.0%) and 19 (90.5%) patients were free from any atrial tachyarrhythmias after single and last procedures. CONCLUSIONS: The LART mechanisms were distinct in individual patients, and elimination of all concomitant ATs was required for the management.

Cryoballoon left atrial roof ablation for persistent atrial fibrillation-Analysis with high-resolution mapping system.

BACKGROUND: Additional benefit of cryoballoon left atrial roof line ablation (CB-RA) beyond cryoballoon pulmonary vein isolation (CB-PVI) is suggested in patients with persistent atrial fibrillation (PsAF). We sought to investigate the feasibility of CB-RA for PsAF and to determine the ablation area. METHODS AND RESULTS: Fifty-three PsAF patients (67[58.5-75.5] years, 36 men, 11 longstanding PsAF) underwent CB-PVI. Subsequently, 44(83.0%) out of 53 patients underwent additional CB-RA. Voltage maps were created in all patients with a high-resolution mapping system. The total number and duration of CB-RAs were 3.9 ± 0.7 and 468 ± 84 s. LA roof areas were complete low voltage areas (LVAs) /scar in 37/44(84.1%) patients ("complete roof modification"). The normal LA posterior wall (LAPW) voltage area was 6.1(4.1-8.4) cm2 , and the %LAPW isolation area was 61.0(47.2-71.7)%. The %LAPW isolation area was significantly greater in CB-RA patients than those without (64.0[54.2-73.2] vs. 45.0[39.5-50.5]%, p = .041) despite significantly larger LAs in the former group. The %LAPW isolation area was significantly greater in patients with transverse LA diameters < 45 mm than those ≥ 45 mm (p < .0001). The single procedure 1-year AF freedom was 87.4% (22.5% on antiarrhythmic drug) and tended to be higher in CB-RA patients than those without. Among the 44 CB-RA patients, it was significantly higher in patients with a complete roof modification than those without (94.4% vs. 75.0%, p = .0049). One CB-RA patient experienced a delayed cardiac tamponade requiring drainage at 4-months post-procedure. CONCLUSIONS: CB-RA significantly expanded the LAPW isolation area, and a complete roof modification resulted in a high arrhythmia freedom in PsAF patients.

Conduction delay across the cavotricuspid isthmus block line caused by the gap near the inferior vena cava: the role of conduction block in the lower lateral right atrium.

The electrophysiological properties of the gap associated with the cavotricuspid isthmus (CTI) block line near the inferior vena cava (IVC) are not fully elucidated. Of 143 patients who underwent CTI block line ablation between September 2020 and April 2021, high-resolution CTI gap mapping was performed for 15 patients. Four patients were identified as having a gap near the IVC (IVC-side gap) despite wide double potentials (DPs) with > 90 ms intervals at the block line. Detailed gap mapping during coronary sinus ostial pacing was performed before and after touch-up ablation. CTI conduction delays caused by an IVC-side gap were classified into 3 patterns: (1) conduction delay at the IVC-side gap without detouring gap conduction, (2) detouring gap conduction due to intrinsic lower lateral right atrium (LLRA)-IVC functional block, and (3) detouring gap conduction due to LLRA-IVC conduction block created by lateral deviation of the CTI ablation line. In Pattern 2, IVC-side gap conduction traveled backward toward the crista terminalis below the LLRA-IVC junction and came back forward again above the border. One patient presented with a head-to-bottom activation pattern of the lateral right atrium (pseudo-CTI block). Pattern 3 was caused by lateral deviation of initial RF deliveries and presented with the same course as intrinsic LLRA-IVC functional block. All patients had wide DP intervals near the tricuspid annulus (mean, 112 ms) and just above the gap site (mean, 109 ms). An IVC-side gap associated with the CTI block line can present with various conduction delay patterns.

Evaluation of interatrial conduction pattern after pulmonary vein isolation using an ultrahigh-resolution electroanatomical mapping system.

Interatrial conduction consists of various muscular bundles, including the Bachmann bundle. In this study, we investigated interatrial activation patterns using ultrahigh-resolution left atrial endocardial mapping. This study investigated 58 patients who underwent catheter ablation of atrial arrhythmia via an ultrahigh-resolution mapping system (Rhythmia) at our hospital from May 2020 to January 2021. Left atrial voltage maps and activation maps were acquired after the ablation procedure during right atrial appendage (RAA) pacing. We defined left atrial breakout sites (LABSs) as centrifugal activation patterns shown by the LUMIPOINT Activation Search Tool. The distance between each LABS in the left atrial anterior wall and the superior border of the interatrial septum (DLABS-IAS) was measured on the shell of the electroanatomical map, and anterior LABSs were divided equally into roof- and septal-side groups. Fifty-three (91%) patients underwent cryoballoon pulmonary vein isolation. Ultrahigh-resolution left atrial mapping was successfully performed in all patients (6831 ± 2158 points). A total of 82 LABSs were identified in left atrial anterior wall; 34 patients had single LABS and 24 patients had dual LABSs. The mean DLABS-IAS was 10.3 ± 9.6 mm. Seven patients also exhibited posterior LABS near the interatrial raphe below the right inferior pulmonary vein. Patients with a single roof-side LABS had significantly shorter left atrial activation times than those with a single septal-side LABS (81.6 ± 13.2 ms vs. 93.5 ± 13.7 ms, p < 0.05). Interatrial conduction patterns during RAA pacing varied between patients and affected the left atrial activation time.

Declines in serum uric acid level after catheter ablation of atrial fibrillation.

BACKGROUND: Few studies have examined whether catheter ablation for AF patients improves biomarkers other than serum levels of brain natriuretic peptide (BNP) and renal function. This study was to explore whether catheter ablation for atrial fibrillation (AF) patients affects uric acid (UA), glucose and lipid metabolism. METHODS AND RESULTS: A total of 206 patients (66.6 ± 10.4 years; 132 men) who underwent initial AF ablation without changes to oral medications were included. Baseline BNP and UA levels significantly decreased at 1 year after ablation (p < 0.05 each). Changes in UA level correlated significantly with pre-procedural UA level (r = 0.57). In multivariable logistic regression modeling, pre-procedural UA level, persistent AF, and hemoglobin A1c (p < 0.05 each) were independent predictors of post-procedural UA level decline. Significant improvements in both persistent and paroxysmal AF patients were identified, and the magnitude of post-procedural serum UA level decline after ablation (ΔUA) was significantly greater in patients with persistent AF (0.8 ± 1.0 mg/dl) than in those with paroxysmal AF (0.2 ± 0.8 mg/dl, p < 0.001). Of the 48 patients with high UA level before procedure, 28 patients showed improvement in UA level to normal range. CONCLUSIONS: Catheter ablation for AF patients significantly improved serum UA levels without obvious influences of heart failure, renal function, or inflammation, suggesting that AF ablation may be effective for AF patients with hyperuricemia. Trial registration The study was approved by the Research Ethics Committee of University of Fukui (no. 20210132) and clinical trial registration (UMIN000044669).

Oral Adrenergic Agents Produced Ventricular Fibrillation and QT Prolongation in an Elderly Patient Carrying an RYR2 Variant.

Mutant cardiac ryanodine receptor channels (RyR2) are "leaky," and spontaneous Ca2+ release through these channels causes delayed afterdepolarizations that can deteriorate into ventricular fibrillation. Some patients carrying RYR2 mutations in type 1 catecholaminergic polymorphic ventricular tachycardia exhibit QT prolongation and are initially diagnosed with long QT syndrome. However, none have been reported to cause drug-induced ventricular fibrillation in patients with RYR2 variants. We describe the first case of an elderly woman with drug-induced QT prolongation and ventricular fibrillation who carried a novel RYR2 variant but no other mutations related to long QT syndrome. Oral adrenergic agents might induce QT prolongation and subsequent ventricular fibrillation in patients carrying an RYR2 variant. Screening for RYR2 could be valuable in patients with suspected drug-induced long QT syndrome.

Abdominal Fat Pad Fine-Needle Aspiration for Diagnosis of Cardiac Amyloidosis in Patients with Non-Ischemic Cardiomyopathy.

The diagnosis of cardiac amyloidosis is frequently delayed because histological confirmation is often challenging. Few studies have attempted to clarify the utility and safety of abdominal fat pad fine-needle aspiration (FPFNA) for an initial screening test in patients with suspected cardiac amyloidosis.This study included 77 consecutive patients with suspected non-ischemic cardiomyopathy who had left ventricular dysfunction and/or hypertrophy. All patients underwent abdominal FPFNA and an endomyocardial biopsy. In all patients, the abdominal FPFNA could be performed within less than 5 minutes with no complications; however, in 1 patient (1.3%), the obtained specimen was too small to evaluate. Among the remaining 76 patients, 5 (6.6%) were positive for amyloid (FPFNA[+]) and 7 (9.2%), including the 5 FPFNA[+], were diagnosed with cardiac amyloidosis (AL = 1, ATTR = 6) by endomyocardial biopsy. Positive abdominal FPFNAs indicated cardiac amyloidosis with high accuracy (sensitivity, 71.4%; specificity, 100%).Positive abdominal FPFNAs are directly linked to diagnoses of cardiac amyloidosis. Abdominal FPFNA is simple and useful for the initial screening test for cardiac amyloidosis in patients with non-ischemic cardiomyopathy.

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome.

BACKGROUND: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. METHODS: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. RESULTS: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5×10-8) near NOS1AP, KCNQ1, and KLF12, and 1 missense variant in KCNE1(p.Asp85Asn) at the suggestive threshold (P<10-6). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (rg=0.40; P=3.2×10-3). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). CONCLUSIONS: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.

Durability of a right superior pulmonary vein isolation after an inevitably interrupted single short freeze during cryoballoon ablation.

BACKGROUND: In cryoballoon ablation, applications for right superior pulmonary veins (RSPVs) inevitably need to be interrupted for some safety reasons. We retrospectively investigated the RSPV isolation durability after single interrupted short freezes. METHODS: Data from 30 patients who underwent repeat procedures 8.2 (4.1-13.8) months after an inevitably interrupted single short freeze (<180 s) for RSPVs during the index cryoballoon procedures were analyzed. It was interrupted by active deflation due to phrenic nerve injury (PNI) (Group 1: n = 14) or passive deflation due to a balloon temperature of -60°C (Group 2: n = 16). RESULTS: The freezing time was 145 (107-166) and 142 (127-160) s and nadir balloon temperature -50.7 ± 3.6 and -60°C in Groups 1 and 2, respectively. Pulmonary vein isolation was achieved after interrupted freezing in all except in one patient requiring touch-up ablation in Group 1. All PNI was asymptomatic and recovered during the follow-up. Eight/13 (61.5%) and 16/16 (100%) RSPVs were durable during the second procedure in Groups 1 and 2. In Group 1, the freezing time was significantly longer in durable than reconnected RSPVs (p = .032), and the optimal cutoff point for the freezing duration to predict the durability was 94.0 s (sensitivity 100%, specificity 60.0%). When the freezing time was ≥120 s, 80% of the RSPVs were durable. However, when the freezing time was ≤68 s, all RSPVs were reconnected. CONCLUSIONS: The feasibility of second cryoapplications for RSPVs should be discussed considering the freezing time of the interrupted initial applications in Group 1, however, it was not necessary in Group 2.

Ultrahigh resolution electroanatomical mapping of the transverse conduction of the right atrial posterior wall in cases with and without typical atrial flutter.

INTRODUCTION: The right atrial posterior wall (RAPW) is known to form a conduction barrier during typical atrial flutter (AFL). We evaluated the transverse conduction properties of RAPW in patients with and without typical AFL using an ultrahigh resolution electroanatomical mapping system. METHODS AND RESULTS: This study included 41 patients who underwent catheter ablation of AF, typical or atypical AFL, in whom we performed RAPW mapping with an ultrahigh resolution mapping system during typical AFL and coronary sinus ostial pacing with three different pacing cycle lengths (PCLs) (1) PCL1: PCL within 40 ms of the AFL cycle length in patients with typical AFL or 250-300 ms for those without, (2) PCL2: 400 ms, (3) PCL3: PCL just faster than the sinus rate. Local RAPW conduction block was evaluated by propagation mapping and local double potentials separated by an isoelectric line. The functional block was defined as areas blocked during shorter PCLs but conductive during longer PCLs. The degree of blockade was calculated by dividing the blocked length by RAPW length (%blockade). Only two patients demonstrated a fixed complete RAPW block (100%, %blockade). Thirty-one patients demonstrated a partial block of RAPW, and the %blockade during PCL1-3 was 49.4 ± 19.8%, 39.5 ± 19.2%, and 35.0 ± 22.9% in this group, respectively. Functional block areas were frequently observed above the fixed block area adjacent to the RA-inferior vena cava junction. Transverse conduction block was more frequently observed in patients with typical AFL at any longitudinal level of RAPW. CONCLUSION: RAPW transverse conduction block is lower-side dominant and greater in patients with typical AFL than those without.