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Cryoablation is safe and effective for the treatment of atrial fibrillation (AF) in controlled clinical trials, but contemporary real-world usage and outcomes are limited. The Report of the Spanish Cryoballoon Ablation Registry (RECABA) was designed to evaluate acute and 12-month outcomes of cryoballoon ablation for the treatment of AF in Spain. Patients from 27 Spanish centers were prospectively enrolled. Patients were treated with cryoballoon ablation and managed according to standard of care protocols at each center. The primary endpoint was ≥ 30 s freedom from AF at 12-month after a 3-month blanking period. Secondary endpoints included a description of patient characteristics, cryoablation procedural strategy and safety, and predictors of efficacy. In total, 1742 patients (71.4% PAF, 68.8% male, mean age 58.02 ± 10.40 years, 76.1% overweight or obese, CHA 2 DS 2 -VASc index 1.40 ± 1.28) were enrolled. Patients received 7.2 ± 2.67 cryo-applications. PV potentials could be detected in 61% of the PVs during ablation, with a mean time to block of 52.9 ± 37.02 s. Acute PVI was observed in 97% of PVs with 75.8% isolated with the first cryo-application. Mean procedural time was 113 ± 41 min. Acute complications occurred in 4.4% of the cases. With follow-up in 1628 patients, AF-free survival was 78.5% (PAF: 80.6% vs PersAF 73.3%; p < 0.001). Left atrium enlargement, female sex, non-PAF, and early recurrence were independent predictors of AF recurrence (p < 0.05). RECABA provides detailed insight into current dosing practices and demonstrates cryoablation is safe and effective in real-world use. ClinicalTrials.gov number : NCT02785991.

Background: The benefit of prophylactic implantable cardioverter defibrillators (ICDs) in patients with severe systolic dysfunction of non-ischemic origin is still unclear, and the identification of patients at risk for sudden cardiac death remains a major challenge. Aims/Methods: We retrospectively reviewed all consecutive patients with non-ischemic dilated cardiomyopathy (NICM) who underwent prophylactic ICD implantation between 2008 and 2020 in two tertiary centers. Our main goal was to identify the predictors of appropriate ICD therapies (anti-tachycardia pacing [ATP] and/or shocks) in this cohort of patients. Results: A total of 224 patients were included. After a median follow-up of 51 months, 61 patients (27.2%) required appropriate ICD therapies. Patients with appropriate ICD therapies were more frequently men (87% vs. 69%, p = 0.006), of younger age (59 years, (53–65) vs. 64 years, (57–70); p = 0.02), showed more right bundle branch blocks (RBBBs) (15% vs. 4%, p = 0.007) and less left bundle branch blocks (LBBBs) (26% vs. 47%, p = 0.005) in the ECG, and had higher left ventricular end-diastolic (100 mL/m2, (90–117) vs. 86, (71–110); p = 0.011) and systolic volumes (72 mL/m2, (59–87) vs. 61, (47–81), p = 0.05). In a multivariate competing-risks regression analysis, RBBB (HR 2.26, CI 95% 1.02–4.98, p = 0.043) was identified as an independent predictor of appropriate ICD therapies. Conclusion: RBBBs may help to identify patients with NICM at high risk of ventricular arrhythmias and requiring ICD intervention.

Synapse-Associated Protein 97 (SAP97) is an anchoring protein that in cardiomyocytes targets to the membrane and regulates Na + and K + channels. Here we compared the electrophysiological effects of native (WT) and p.P888L SAP97, a common polymorphism. Currents were recorded in cardiomyocytes from mice trans-expressing human WT or p.P888L SAP97 and in Chinese hamster ovary (CHO)-transfected cells. The duration of the action potentials and the QT interval were significantly shorter in p.P888L-SAP97 than in WT-SAP97 mice. Compared to WT, p.P888L SAP97 significantly increased the charge of the Ca-independent transient outward (I to,f ) current in cardiomyocytes and the charge crossing Kv4.3 channels in CHO cells by slowing Kv4.3 inactivation kinetics. Silencing or inhibiting Ca/calmodulin kinase II (CaMKII) abolished the p.P888L-induced Kv4.3 charge increase, which was also precluded in channels (p.S550A Kv4.3) in which the CaMKII-phosphorylation is prevented. Computational protein-protein docking predicted that p.P888L SAP97 is more likely to form a complex with CaMKII than WT. The Na + current and the current generated by Kv1.5 channels increased similarly in WT-SAP97 and p.P888L-SAP97 cardiomyocytes, while the inward rectifier current increased in WT-SAP97 but not in p.P888L-SAP97 cardiomyocytes. The p.P888L SAP97 polymorphism increases the I to,f , a CaMKII-dependent effect that may increase the risk of arrhythmias.

Sudden cardiac arrest (SCA) is an uncommon but devastating event among young adults. While inherited cardiomyopathies and channelopathies represent an important proportion of sudden deaths, coronary artery disease remains a significant contributor in this age group. ECG findings are essential to guide the first steps of diagnostic work‐up of SCA, but sometimes can overlap between different etiologies. In this article we present a 16‐year‐old female who experienced SCA during vigorous swimming whose ECG was compatible with long QT syndrome. However, evaluation of the coronary anatomy provided the diagnosis of Kawasaki disease. Sudden cardiac arrest is uncommon among young adults. Inherited cardiomyopathies and channelopathies are the most frequently identified cardiac etiologies. However, assessment of coronary artery anatomy is mandatory in order to rule out coronary artery anomalies.

We present the first reported case of extraction of a ventricular lead placed in the left bundle branch area with a double-loop design snare via the femoral approach without any complication. It was a 4-month-old lead whose extraction was not possible only with a conventional stylet via an implant vein approach, so we want to show that complete procedural success is possible.

BACKGROUND: Freezing rate of second-generation cryoballoon (CB) is a biophysical parameter thatcould assist pulmonary vein isolation. The aim of this study is to assess freezing rate (time to reach–30°C ([TT-30C]) as an early predictor of acute pulmonary vein isolation using the CB. METHODS: Biophysical data from CB freeze applications within a multicenter, nation-wide CB ablationregistry were gathered. Successful application (SA), was defined as achieving durable intraprocedural veinisolation. And SA with time to isolation under 60 s (SA-TTI<60) as achieving durable vein isolation inunder 60 s. Logistic regressions were performed and predictive models were built for the data set. RESULTS: 12,488 CB applications from 1,733 atrial fibrillation (AF) ablation procedures were includedwithin 27 centers from a Spanish CB AF ablation registry. SA was achieved in 6,349 of 9,178 (69.2%)total freeze applications, and SA-TTI<60 was obtained in 2,673 of 4,784 (55.9%) freezes where electrogrammonitoring was present. TT-30C was shorter in the SA group (33.4 ± 9.2 vs 39.3 ± 12.1 s;p < 0.001) and SA-TTI<60 group (31.8 ± 7.6 vs. 38.5 ± 11.5 s; p < 0.001). Also, a 10 s increase inTT-30C was associated with a 41% reduction in the odds for an SA (odds ratio [OR] 0.59; 95% confidenceinterval [CI] 0.56–0.63) and a 57% reduction in the odds for achieving SA-TTI<60 (OR 0.43;95% CI 0.39–0.49), when corrected for electrogram visualization, vein position, and application order. CONCLUSIONS: Time to reach –30°C is an early predictor of the quality of a CB application and can beused to guide the ablation procedure even in the absence of electrogram monitoring.

Ablation of atrial fibrillation (AF), both cryoablation ablation (CBA) and radiofrequency catheter ablation (RFCA), have demonstrated to be safe and effective. About 1 in 3 patients may face a redo due to recurrence and the best technique is unknown. The aim of this study is to assess the efficacy of CBA as a repeat procedure in patients with prior CBA or RFCA. A nation-wide CBA registry (RECABA) was analyzed and patients were compared who had previously undergone CBA (Prior-CB) or RFCA (Prior-RF). The primary endpoint was AF recurrence at 12 months after a 3-month blanking period. A survival analysis was performed, univariate and multivariate Cox models were also built. Seventy-four patients were included. Thirty-three (44.6%) were in the Prior-CB group and 41 (55.4%) in the Prior-RF. There were more reconnected pulmonary veins in the Prior-RF than in Prior-CB group (40.4% vs.16.5%, p = 0.0001). The 12-month Kaplan-Meier estimate of freedom from AF recurrence after the blanking period was 61.0% (95% confidence interval [CI] 41.4-75.8%) in the Prior-CB, and 89.2% (95% CI 73.6-95.9%) in the Prior-RF group (p = 0.002). Multivariate Cox regression pointed Prior-CB as the sole independent predictor of AF recurrence, with an adjusted HR of 2.67 (95% CI 1.05-6.79). Repeat CBA shows higher rates of AF recurrences compared to CBA after a previous RFCA despite presenting less reconnected veins at the procedure. These data suggest that patients with AF recurrence after CBA may benefit from other ablation techniques after a recurrence. RECABA is registered at clinicaltrials.gov with the Unique Identifier NCT02785991.

ObjectiveWe sought to investigate prevalence, incidence and prognostic implications of permanent pacemaker (PPM) implantation in patients with cardiac amyloidosis (CA), thereby identifying the predictors of time to PPM implantation.MethodsSeven hundred eighty-seven patients with CA (602 men, median age 74 years, 571 transthyretin amyloidosis (ATTR), 216 light-chain amyloidosis (AL)) evaluated at two European referral centres were retrospectively included. Clinical, laboratory and instrumental data were analysed. The associations between PPM implantation and mortality, heart failure (HF) or a composite endpoint of mortality, cardiac transplantation and HF were analysed.Results81 (10.3%) patients had a PPM before initial evaluation. Over a median follow-up time of 21.7 months (IQR 9.6–45.2), 81 (10.3%) additional patients (18 with AL (22.2%) and 63 with ATTR (77.8%)) underwent PPM implantation with a median time to implantation of 15.6 months (IQR 4.2–40), complete atrioventricular block was the most common indication (49.4%). Independent predictors of PPM implantation were QRS duration (HR 1.03, 95% CI 1.02 to 1.03, p<0.001) and interventricular septum (IVS) thickness (HR 1.1, 95% CI 1.03 to 1.17, p=0.003). The model to estimate the probability of PPM at 12 months and containing both factors showed a C-statistic of 0.71 and a calibration of slope of 0.98.ConclusionsConduction system disease requiring PPM is a common complication in CA that affects up to 20.6% of patients. QRS duration and IVS thickness are independently associated with PPM implantation. A PPM implantation at 12 months model was devised and validated to identify patients with CA at higher risk of requiring a PPM and who require closer follow-up.

BackgroundHypertension is an important, modifiable risk factor for the development of atrial fibrillation (AF). Even after pulmonary vein isolation (PVI), 20–40% experience recurrent AF. Animal studies have shown that renal denervation (RDN) reduces AF inducibility. One clinical study with important limitations suggested that RDN additional to PVI could reduce recurrent AF.ObjectiveThe goal of this multicenter randomized controlled study is to investigate whether RDN added to PVI reduces AF recurrence.MethodsThe main end point is the time until first AF recurrence according to EHRA guidelines after a blanking period of 3 months. Assuming a 12-month accrual period and 12 months of follow-up, a power of 0.80, a two-sided alpha of 0.05 and an expected drop-out of 10% per group, 69 patients per group are required. We plan to randomize a total of 138 hypertensive patients with AF and signs of sympathetic overdrive in a 1:1 fashion. Patients should use at least two antihypertensive drugs. Sympathetic overdrive includes obesity, exercise-induced excessive blood pressure (BP) increase, significant white coat hypertension, hospital admission or fever induced AF, tachycardia induced AF and diabetes mellitus. The interventional group will undergo PVI + RDN and the control group will undergo PVI.ResultsPatients will have follow-up for 1 year, and continuous loop monitoring is advocated.ConclusionThis randomized, controlled study will elucidate if RDN on top of PVI reduces AF recurrence.

The ZFHX3 and SCN5A genes encode the zinc finger homeobox 3 (Zfhx3) transcription factor (TF) and the human cardiac Na+ channel (Nav1.5), respectively. The effects of Zfhx3 on the expression of the Nav1.5 channel, and in cardiac excitability, are currently unknown. Additionally, we identified three Zfhx3 variants in probands diagnosed with familial atrial fibrillation (p.M1260T) and Brugada Syndrome (p.V949I and p.Q2564R). Here, we analyzed the effects of native (WT) and mutated Zfhx3 on Na+ current (INa) recorded in HL-1 cardiomyocytes. ZFHX3 mRNA can be detected in human atrial and ventricular samples. In HL-1 cardiomyocytes, transfection of Zfhx3 strongly reduced peak INa density, while the silencing of endogenous expression augmented it (from −65.9 ± 8.9 to −104.6 ± 10.8 pA/pF; n ≥ 8, p < 0.05). Zfhx3 significantly reduced the transcriptional activity of human SCN5A, PITX2, TBX5, and NKX25 minimal promoters. Consequently, the mRNA and/or protein expression levels of Nav1.5 and Tbx5 were diminished (n ≥ 6, p < 0.05). Zfhx3 also increased the expression of Nedd4-2 ubiquitin-protein ligase, enhancing Nav1.5 proteasomal degradation. p.V949I, p.M1260T, and p.Q2564R Zfhx3 produced similar effects on INa density and time- and voltage-dependent properties in WT. WT Zfhx3 inhibits INa as a result of a direct repressor effect on the SCN5A promoter, the modulation of Tbx5 increasing on the INa, and the increased expression of Nedd4-2. We propose that this TF participates in the control of cardiac excitability in human adult cardiac tissue.