Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the causes of sudden cardiac death in young people and results from RYR2 mutations in ~60% of CPVT patients. The inheritance of ...the RYR2 mutations follows an autosomal dominant trait, however, de novo mutations are often identified during familial analysis. In 36 symptomatic CPVT probands with RYR2 mutations, we genotyped their parents and confirmed the origin of the respective mutation. In 26 sets of proband and both parents (trio), we identified 17 de novo mutations (65.4%), seven from their mothers and only two mutations were inherited from their fathers. Among nine sets of proband and mother, five mutations were inherited from mothers. Four other mutations were of unknown origin. The inheritance of RYR2 mutations was significantly more frequent from mothers (n = 12, 34.3%) than fathers (n = 2, 5.7%) (P = 0.013). The mean ages of onset were not significantly different in probands between de novo mutations and those from mothers. Thus, half of the RYR2 mutations in our cohort were de novo, and most of the remaining mutations were inherited from mothers. These data would be useful for family analysis and risk stratification of the disease.
Acquired long QT syndrome (aLQTS) exhibits QT prolongation and Torsades de Pointes ventricular tachycardia triggered by drugs, hypokalaemia, or bradycardia. Sometimes, QTc remains prolonged despite ...elimination of triggers, suggesting the presence of an underlying genetic substrate. In aLQTS subjects, we assessed the prevalence of mutations in major LQTS genes and their probability of being carriers of a disease-causing genetic variant based on clinical factors.
We screened for the five major LQTS genes among 188 aLQTS probands (55 ± 20 years, 140 females) from Japan, France, and Italy. Based on control QTc (without triggers), subjects were designated 'true aLQTS' (QTc within normal limits) or 'unmasked cLQTS' (all others) and compared for QTc and genetics with 2379 members of 1010 genotyped congenital long QT syndrome (cLQTS) families. Cardiac symptoms were present in 86% of aLQTS subjects. Control QTc of aLQTS was 453 ± 39 ms, shorter than in cLQTS (478 ± 46 ms, P < 0.001) and longer than in non-carriers (406 ± 26 ms, P < 0.001). In 53 (28%) aLQTS subjects, 47 disease-causing mutations were identified. Compared with cLQTS, in 'true aLQTS', KCNQ1 mutations were much less frequent than KCNH2 (20% 95% CI 7-41% vs. 64% 95% CI 43-82%, P < 0.01). A clinical score based on control QTc, age, and symptoms allowed identification of patients more likely to carry LQTS mutations.
A third of aLQTS patients carry cLQTS mutations, those on KCNH2 being more common. The probability of being a carrier of cLQTS disease-causing mutations can be predicted by simple clinical parameters, thus allowing possibly cost-effective genetic testing leading to cascade screening for identification of additional at-risk family members.
Experimental data suggest that cryoenergy is associated with less endothelial damage and thrombus formation than radiofrequency energy. This study aimed to compare the impact of pulmonary vein ...isolation (PVI) on the endothelial damage, myocardial damage, inflammatory response, and prothrombotic state between the two latest technologies, second-generation cryoballoon (CB2) and contact force-sensing radiofrequency catheter (CFRF) ablation. Eighty-six paroxysmal atrial fibrillation (AF) patients (55 men; 65 ± 12 years) underwent PVI with either the CB2 (
n
= 64) or CFRF (
n
= 22). Markers of the endothelial damage (
l
-arginine/asymmetric dimethylarginine ADMA), myocardial injury (creatine kinase-MB CK-MB, troponin-T, and troponin-I), inflammatory response (high-sensitive C-reactive protein), and prothrombotic state (D-dimer, soluble fibrin monomer complex, and thrombin–antithrombin complex) were determined before and up to 24-h post-procedure. The total application time was shorter (1,460 ± 287 vs. 2,395 ± 571 sec,
p
< 0.01) and total procedure time tended to be shorter (199 ± 37 vs. 218 ± 38 min,
p
= 0.06) with CB2 than CFRF ablation. The amount of myocardial injury was greater (CK-MB: 45 ± 17 vs. 11 ± 3 IU/l,
p
< 0.01) with CB2 than CFRF ablation. The
l
-arginine/ADMA ratio was lower (160 ± 51 vs. 194 ± 38,
p
= 0.028) after CB2 than CFRF ablation. Inflammatory and all prothrombotic markers were significantly elevated post-ablation; however, the magnitude was similar between the two groups. During a mean follow-up of 20 ± 6 months, the single-procedure AF freedom was similar between the CB2 and CFRF groups (60/64 vs. 20/22,
p
= 0.82). CB2-PVI produces significantly lesser endothelial damage with greater myocardial injury than CFRF-PVI; however, similar anticoagulant regimens are required during the peri-procedural periods in both technologies.
Aim: The aim of this study was to examine the effects of evolocumab on favorable limb events in patients with chronic limb-threatening ischemia (CLTI). Methods: A single-center, prospective ...observational study was performed on 30 patients with CLTI. The subjects were divided into 2 groups based on evolocumab administration: evolocumab-treated (E) group ( n=14) and evolocumab non-treated (non-E) group (n=16). The primary outcome was 12-month freedom from major amputation. The secondary outcomes were 12-month amputation-free survival (AFS), overall survival (OS), and wound-free limb salvage. The mean follow-up period was 18±11 months. Results: No significant difference was detected between the two groups for the 12-month freedom from major amputation (log-rank p=0.15), while the 12-month AFS rate was significantly higher in the E group than that in the non-E group (log-rank p=0.02). The 12-month OS rate in the E group was shown a tendency for improvement, as compared with that in the non-E group (log-rank p=0.056). Evolocumab administration was not associated with a significant change in freedom from major amputation (HR, 0.23, 95% CI, 0.03-2.07, p=0.19). However, evolocumab administration was related to a tendency for improvement of AFS and OS (HR, 0.13, 95% CI, 0.02-1.06, p=0.056; HR, 0.16, 95% CI, 0.02-1.37, p=0.09, respectively). Moreover, The E group had a higher proportion of wound-free limb salvage at 12 months (92% vs. 42%, p=0.03). Conclusion: Evolocumab administration was associated with a better AFS outcome in patients with CLTI. Long-term administration of evolocumab over 12 months contributed to improving proportion of wound-free limb salvage.
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.
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.
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