Efficacy and safety of novel left ventricular pacing leads: 1-year analysis of the NAVIGATOR trial.

OBJECTIVES: Assess safety and performance of novel quadripolar preshaped left ventricular (LV) leads: NAVIGO 4LV 2D ('S shaped') and NAVIGO 4LV ARC ('U shaped'). METHODS: Patients indicated for cardiac resynchronisation therapy were enrolled in a multicentre, prospective, controlled study (NAVIGATOR, NCT03279484). Patients were implanted with either a NAVIGO 4LV 2D or ARC lead, and assessed at 10 weeks, 6, 12 and 24 months post-implant. Co-primary safety and performance endpoints were assessed at 10 weeks. Safety endpoint was the patients' rate free from lead-related complications. Performance endpoint was the rate of patients with successful lead performance, defined as LV pacing threshold ≤2.5 V at 0.5 ms on at least one pacing vector, and the absence of phrenic nerve stimulation at the final programmed configuration. Lead-related complications and electrical parameters were monitored throughout study. RESULTS: A NAVIGO 4LV lead was successfully implanted in 211 out of 217 patients (97.2%). The safety endpoint was met, with 100% and 96.1% of patients free from complications for NAVIGO 4LV 2D and ARC, respectively. The performance endpoint was met with 98.1% and 98.9% of patients with a successful lead performance for NAVIGO 4LV 2D and ARC, respectively. Over 12 months, the global complication-free rate for both leads was 97.1% (95% CI: 93.71% to 98.70%), with a mean pacing capture threshold of 1.23 V±0.73 V and a mean impedance of 951 Ω±300.1 Ω. CONCLUSION: A high implantation success rate and low complication rate was reported for the novel NAVIGO 4LV 2D and ARC leads, along with successful performance up to 12 months.

Age-associated polyamines in peripheral blood cells and plasma in 20 to 70 years of age subjects.

Dietary polyamines have been associated with slowing ageing processes and various pathologies, raising the importance of establishing reference values at different ages throughout life. This study aimed to analyse age-dependent variations in polyamine content using peripheral blood cells and plasma in a healthy and homogeneous population. Peripheral blood of 193 volunteers of both sexes (20-70 years), selected by convenience, was processed to separate cells and plasma. A pre-column derivatization method was used to determine the amines by HPLC (nmol or pmol/mg protein or nmol/ml) to analyse their association with the age (continuous or ordinal in decades) of the subjects. Putrescine and spermine weakly declined significantly in mononuclear cells with age. In erythrocytes and plasma, putrescine showed an evident decrease in the 60-70-year-old group compared to the rest. The ratios between polyamines, mainly in erythrocytes, decreased in the 60-70 years age group and increased the ratio of putrescine in mononuclear cells/erythrocytes. The ratio of putrescine in mononuclear cells/erythrocytes was higher in the 60-70-year-old age group than in the rest. In a sample of subjects (20-29 vs. 60-70 years), whole blood polyamines were not significantly different when differences existed in erythrocytes. Polyamine homeostasis in blood cells and plasma changed with age. Putrescine declined in mononuclear cells and decreased in erythrocytes and plasma in the decade of the 60 s. Further studies should establish an age-dependent phenotype and whether polyamines' supplementation could restore the decreased values and be associated with long-term overall biological benefits.

KCNH2 p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort.

Long QT syndrome (LQTS) is an inherited (autosomal dominant) channelopathy associated with susceptibility to ventricular arrhythmias due to malfunction of ion channels in cardiomyocytes, that could lead to sudden death (SD). Most pathogenic variants are in the main 3 genes: KCNQ1 (LQT1), KCNH2 (LQT2) and SCN5A (LQT3). Efforts to improve the understanding of the genotype-phenotype relationship are essential to improve the medical clinical practice. In this study, we identified all index patients referred for NGS genetic sequencing due to LQTS, in a Spanish cohort, who were carriers of a new pathogenic variant (KCNH2 p.Gly262AlafsTer98). Genetic and clinical family screening was performed in order to describe its phenotypic characteristics. We identified 22 relatives of Romani ethnicity, who were carriers of the variant. Penetrance reached a 100% and adherence to medical treatment was low. There was a high rate of clinical events, particularly arrhythmic events and SD (1 in every 4 patients presented syncope, 1 presented an aborted SD, 2 obligated carriers suffered SD before the age of 40 and 4 out of 6 carriers of an implantable cardioverter-defibrillator (ICD) had appropriate ICD therapies. Correct adherence to medical treatment in all carriers should be specially encouraged in this population. ICD implantation decision in non-compliant patients, and refusing left cardiac sympathetic denervation, should be carefully outweighed.

Left-Right ambiguity resolution for coprime sparse arrays.

Coprime Sparse Arrays (CSA) with two collocated uniform linear arrays are used to estimate O(MN) direction of arrivals for a narrow band source with only O(M+N) sensors. The CSA cannot discriminate the azimuth and its complementary angles due to the symmetry along the array-axis. The bearing ambiguity, also referred to as a Left-Right (LR) ambiguity, is addressed in this paper using CSA. We design Left-Right resolved Coprime Sparse Arrays (LRCSA) to produce a null that is electronically steered to the complementary angle of the desired direction. LRCSA twin array achieves higher spatial resolution than the conventional fully populated LR array with same number of sensors, much like the collocated CSA. Three methods, namely, Null Constrained Beamformer (NCB), two-dimensional Direct Beamformer (2DDB), and LRCSA are studied. The bound on the detection gain is analytically established for the LRCSA under correlated noise scenarios modeled by the first-order autoregressive process. Twin array processing using the LRCSA method results in narrow mainlobe beam width along with a higher rejection ratio (RR) compared to 2DDB and NCB. Data obtained from a sea experiment using a towed array is analyzed. The results confirm that the CSA based cardioid processing resolved LR ambiguity along with a higher RR and narrower beams.

Rationale and design of the rigorous atrial analysis in advanced interatrial block (ARABIA) prospective study.

BACKGROUND: Advanced interatrial block (IAB) is present in 10% of subjects ≥75 years and is associated with the risk of clinical events. METHODS AND RESULTS: Prospective multicenter study that will include subjects ≥75 years without exclusion criteria (indication for anticoagulation, cardiac devices, severe valve disease, systolic dysfunction, moderate or severe cognitive impairment, poor echocardiographic window, non-sinus rhythm or partial IAB, stroke, and life expectancy <2 years). A total of 356 subjects, 178 patients with advanced IAB (exposed) and 178 matched individuals with normal P-wave (non-exposed) will be included. Electrocardiogram and advanced transthoracic echocardiography will be performed. Two substudies will include magnetic resonance imaging: cardiac (86 subjects, 43 exposed, and 43 non-exposed) and brain (86 subjects, 43 exposed, and 43 non-exposed). The follow-up will be 2 years. Our main objective is to determine the association of advanced IAB, P-wave duration, and atrial imaging parameters (I] atrial global longitudinal strain, II] maximal left atrial volume index, III] left atrial ejection fraction, IV] left atrial fibrosis - % total left atrial area V] inter- and intra-atrial asynchrony/dyssynchrony) with clinical events (atrial fibrillation, stroke, cognitive impairment, and mortality). The secondary objective is to assess the association of the P-wave duration with atrial imaging parameters and of both with cerebral microemboli in magnetic resonance imaging. CONCLUSION: Our study will provide data regarding the association of advanced IAB, P-wave duration, and atrial imaging parameters with clinical events. We will also assess the association P-wave duration-atrial imaging parameters-cerebral microemboli.

The clinical impact of untreated slow ventricular tachycardia in patients carrying implantable cardiac defibrillators.

INTRODUCTION: The clinical impact of slow ventricular tachycardia (VT), occurring in patients carrying implantable cardiac defibrillators (ICD), is still under debate. METHODS AND RESULTS: From the UMBRELLA registry (multicenter, observational, and prospective study on patients with ICD), 659 episodes of slow VT were observed in 97 patients. Untreated slow VT (n = 93) had longer duration (23.7 min, CI95%: 10-39), compared with episodes treated effectively by anti-tachycardia pacing (ATP; n = 527; 0.32 min, IC95%: 0.22-0, 48) or shock (n = 39; 1 min, CI95%: 0.8-1.2). Despite of longer duration, the time to the first contact with the medical services was similar to those episodes treated by ATP (50 days [CI95%: 45-55] vs. 41 days [CI95%: 39-44]). However, both were significantly longer than the time observed in episodes treated with shock (10 days, CI95%: 6-15). This tendency was maintained with successive interrogations of the device (2nd and 3rd). There were no significant differences in mortality during follow-up (48 ± 16 months), neither other adverse outcomes, between patients who presented untreated slow TV and those who did not (log-rank p = 0.28). In a Cox regression analysis, the variable "presenting untreated episodes of slow VT" was not able to predict mortality. However, being in sinus rhythm (vs. atrial fibrillation, OR: 0.31, p = 0.009), narrower QRS (OR: 1.036, p = 0.037) and diabetes (OR 4.673, p = 0.049) appropriately predict survival. CONCLUSIONS: Untreated slow VT does not significantly worsen patient prognosis. Our results support the limitation of therapies to ATP only, thus avoiding therapies that have been associated with increased risk of morbidity and mortality.

Spectral Analysis of the QT Interval Increases the Prediction Accuracy of Clinical Variables in Brugada Syndrome.

(1) Background: The clinical management of Brugada Syndrome (BrS) remains suboptimal. (2) Objective: To explore the role of standard electrocardiogram (ECG) spectral analysis in diagnosis and risk stratification. (3) Methods: We analyzed 337 patients-43 with a spontaneous type I ECG pattern (Spont-BrS), 112 drug induced (Induct-BrS), and 182 with a negative response to the drug challenge (negative responders (NR)). ECGs were processed using the wavelet transform (high frequency: 85 to 130 Hz). (4) Results: The power of the high-frequency content in the ST segment (Total ST Power; nV²Hz-¹10³) was higher in BrS compared with NR patients (Spont-BrS: 28.126 (7.274-48.978) vs. Induc-BrS: 26.635 (15.846-37.424) vs. NR: 11.13 (8.917-13.343); p = 0.002). No differences were observed between ECG patterns in BrS patients. However, the Total ST Power of the type II or III ECG in NR patients was lower than in the same ECG patterns recorded from BrS patients (BrS: 31.07 (16.856-45.283); vs. NR: 10.8 (7.248-14.352) nV²Hz-¹10³; p = 0.007). The Total ST Power, age, and family history of BrS were independent predictors of positive responses to drug testing. Comparing models with versus those without Total ST Power, the area under the received operator curve (ROC) curve increased (with 0.607 vs. without 0.528, p = 0.001). Only syncope was associated with an increased risk (follow-up 55.8 ± 39.35 months). However, the area under the ROC curve increased significantly when the Total ST Power was included as a covariate (with 0.784 vs. without 0.715, p = 0.04). (5) Conclusions: The analysis of the high-frequency content of ECG signals increases the predictive capability of clinical variables in BrS patients.

The QT Interval Dynamic in a Human Experimental Model of Controlled Heart Rate and QRS Widening.

Background: there is increasing interest for computing corrected QT intervals in patients with prolonged depolarization. We aimed to analyze the effect of prolonged QRS in the QT and in the diagnostic accuracy of frequency-correction. Methods and Results: in 28 patients admitted for self-expanding aortic valve implantation, sequential pacing was performed in the AAI mode in two different phases: before and immediately after the release of the prosthesis. We evaluated the accuracy of the Bazett, Fridericia, Framingham and Hodges formulas with the reference of the QT at 60 bpm (QTc/deviation). The widening of the QRS was the main contributor to the QT prolongation (Pearson 0.79; CI95%: 0.75-0.84). Prolongation in other intervals (ST segment and T-wave) significantly contribute in the higher frequency range (p < 0.05). The Bazett's formula displayed the highest QTc/deviation, while Framingham and Hodges retrieved the lowest QTc/deviation and the best fit (p < 0.001). In addition, the Bazett's formula displayed the highest correlation between variations in the QTc/deviation and the widening of the QRS (Pearson coefficient -0.54; p < 0.001) in comparison with the Fridericia, Framingham and Hodges formulas (-0.51, -0.37 and -0.38 respectively; p < 0.001). There was also a linear effect of the heart rate in the QTc/deviation obtained with the Bazett's formula (p = 0.015), not observed for other formulas. Conclusions: The prolonged depolarization of the ventricles introduces direct and linear prolongation in the QT interval, but also a non-linear distortion in cardiac repolarization that contributes for QT prolongation at the higher frequency range. The Bazett's formula displays significantly higher sensitivity to prolongation of ECG intervals.

Insights for Stratification of Risk in Brugada Syndrome.

Brugada syndrome (BrS) is an inherited disease with an increased risk of sudden cardiac death (SCD). However, testing identifies genetic disorders in only 20-30% of patients analysed, indicating a gap in knowledge of its genetic aetiology. Diagnosis relies on ECG, and risk stratification in BrS patients is challenging, primarily because of the complexity of the issue. As a result, clinicians fail to provide the appropriate strategy for SCD prevention for many patients. Several variables and interventions are being studied to improve diagnostics and maximise patient protection. In addition, the scientific community must increase efforts to provide patient care according to knowledge and research for improving stratification of risk. In this article, the authors summarise contemporary evidence on clinical variables and provide an overview of future directions in risk stratification and SCD prevention.

Acciones de wrongful conception en Chile: una propuesta de fundamentación / Wrongful conception claims in Chile: a proposal for their justification / Ações de wrongful conception no Chile: uma proposta de fundamentação

Resumen: En el presente artículo, los autores tratan el tópico de admisibilidad en Chile de las acciones de responsabilidad civil de wrongful conception o anticoncepciones fallidas. Utilizando referencias hacia la práctica en el derecho comparado y al derecho internacional de los derechos humanos, los autores argumentan a favor de fundamentar su reparación en el derecho a la autodeterminación reproductiva de las mujeres.

Abstract: In this article, the authors refer to the wrongful conception claims, particularly the controversy of their admission in Chile. On the basis of comparative and human rights international law, the authors argue in favor of the women's right to reproductive self-determination as the foundation of their compensation.

Resumo: Neste artigo, os autores abordam o tema da admissibilidade no Chile das ações de responsabilidade civil de wrongful conception ou anticoncepções fracassadas. Com base em referências para a prática no direito comparado e no direito internacional dos direitos humanos, os autores argumentam a favor de fundamente sua reparação o direito à autodeterminação reprodutiva das mulheres.

Analysis of early failure of Biotronik Linox Smart implantable cardioverter-defibrillator leads: A comparative study of three defibrillator leads.

BACKGROUND AND OBJECTIVES: Early failure of Biotronik Linox and Linox Smart leads (Biotronik, Berlin, Germany) has been reported in numerous recent publications. The aim of this study was to assess the performance of this lead compared with that of two other contemporary leads. METHODS: We conducted an ambispective study of all consecutive first implantations of defibrillator leads carried out in our center: Endotak (model 148, 158, Boston Scientific, Marlborough, MA, USA) (n = 173), Sprint Quattro (model 6644, 6947, Medtronic, Dublin, Ireland) (n = 145), and Linox Smart (Biotronik, model SD 65/16) (n = 120). RESULTS: During a median follow-up of 4.6 ± 2.1 years, failure occurred in nine Linox Smart (7.5%), one Endotak Reliance (0.6%), and no Sprint Quattro leads. The survival probability of the Linox Smart group was significantly lower than that of the Endotak and Sprint Quattro groups measured by the log-rank test (Linox vs Endotak; P < 0.001 and Linox vs Sprint Quattro; P < 0.001). Nonphysiological signals not due to external interference were observed in all Linox Smart leads, with normal parameters and without visible anomalies on chest x-ray. CONCLUSIONS: In this single-center experience, the survival rate of Linox Smart leads was 88% at 5 years of follow-up, which was significantly lower than that of the other leads. Comprehensive vigilance of Linox Smart leads, including home monitoring, may be advisable to facilitate early detection of lead failure and avoid inappropriate shocks.

Role of syncope in predicting adverse outcomes in patients with suspected Brugada syndrome undergoing standardized flecainide testing.

Aims: Sensitivity to flecainide testing results in suboptimal findings in patients with Brugada syndrome (BrS), leading to safety concerns. Because cardiac syncope effectively predicts outcomes in BrS, we aimed to explore its predictive value in a large cohort of negative and positive responders (NR and PR) to standard flecainide testing. Methods and results: We analysed the data of 251 consecutive patients, 177 NR vs. 74 PR, to flecainide testing, performed according to standard recommendations. Cardiac syncope was defined as syncope presenting without prodromal symptoms and in the absence of any specific situation. Comparing PR with NR, there were no differences regarding age (39 ± 15 vs. 44 ± 13 years; P = 0.052), male gender (70.1% vs. 66.2%; P = 0.553), and family history of sudden cardiac death in relatives younger than 45 years (27% vs. 27%; P = 1). Cardiac syncope was more frequent in PR (12.2% vs. 4%; P = 0.022), and previous sudden cardiac arrest (SCA) was documented only in PR (5.4% vs. 0%; P = 0.007). During the follow-up period (6.2 ± 3.3 years), one NR, who had previously experienced cardiac syncope, developed SCA 3 months after flecainide testing. Following resuscitation, a type I electrocardiogram was spontaneously recorded. The follow-up event rate was higher in patients with cardiac syncope, both in PR and in NR (P < 0.001 both). In a multivariate analysis, cardiac syncope was the unique variable that predicted adverse outcomes (hazard ratio 14.9, 95% confidence interval 1.84-121.25; P = 0.011). Conclusions: In patients with false-negative responses to the provocative testing with flecainide, cardiac syncope predicts SCA, allowing a more extensive and individualized evaluation.

Delta of the local ventriculo-atrial intervals at the septal location to differentiate tachycardia using septal accessory pathways from atypical atrioventricular nodal re-entry.

Aims: Tachycardia mediated by septal accessory pathways (AP) and atypical atrioventricular nodal re-entry (AVNRT) require careful electrophysiologic evaluation for differential diagnosis. We aim to describe the differential behaviour of local ventriculo-atrial (VA) intervals which predicts the tachycardia mechanism. Methods and results: The local VA intervals at the para-Hisian septum were measured under three different situations: (i) tachycardia; (ii) sustained entrainment from the right ventricular apex (RVA); and (iii) continuous pacing from the RVA during sinus rhythm. Differences were computed as follows: Δ-VAentr = VA during entrainment - VA during tachycardia; and Δ-VApac = VA while pacing during sinus rhythm - VA during tachycardia. In contrast to AVNRT, we hypothesized that an invariable retrograde conduction through the septal AP will keep the result of the subtractions close to 0 ms in cases of ortodromic atrioventricular re-entrant tachycardia (AVRT). We analysed 55 atypical AVNRT (45% posterior type) and 82 AVRT (10 anteroseptal, 18 para-Hisian, 12 mid-septal, and 42 posteroseptal). Δ-VAentr was longer for AVNRT (98.5 ± 40.3 ms) compared with septal AP (-5.7 ± 19.3 ms; P < 0.001). A value of 50 ms showed 98.7% sensitivity and 92% specificity (AUC 0.99; 95% CI 0.98-1). According to physiological criteria, a negative Δ-VAentr remains unobserved in the case of AVNRT (positive predictive value 100% for septal AP). Δ-VApac was also longer for AVNRT (66.5 ± 14.6 ms) compared with septal AP (-9.7 ± 3.3 ms; P < 0.001). A value of 50 ms showed 100% sensitivity and 74% specificity (AUC 0.86; 95% CI 0.76-0.93). Conclusions: Delta of the local VA intervals enables distinction between atypical AVNRT and AVRT mediated by septal AP.

Ablation of Rotor Domains Effectively Modulates Dynamics of Human: Long-Standing Persistent Atrial Fibrillation.

BACKGROUND: In human long-standing persistent atrial fibrillation, rotors potentially explain atrial fibrillation maintenance, but their ablation remains controversial. We aimed to explore original phase/frequency mapping methods to locate rotors and track changes induced by their ablation. METHODS AND RESULTS: Thirteen patients with long-standing persistent atrial fibrillation (duration, 12-72 months) underwent phase/frequency mapping (Hilbert/Fourier transforms; CARTO-Finder) of the left and right atria (PentaRay catheter). A rotor domain was defined as an area displaying at least 3 consecutive rotations. Ablation was performed by circumferential pulmonary vein isolation plus linear ablation of extrapulmonary rotor domains. We identified 19 rotor domains in 10 patients (1.8±1.1 per patient; 7 in the right atrium versus 12 in the left atrium; 15 extrapulmonary). Overall, rotor domains (9.2±2.2 rotations) displayed higher frequency of activation (6.41 Hz; 95% confidence interval, 6.24-6.57) than nonrotor domains (6.17 Hz; 95% confidence interval, 6.1-6.23; P=0.021), with interatrial frequency gradients established by the spatial location of the rotor domain (P=0.016). Fibrillatory conduction was suggested as a decrease in the frequency of the slower atria after ablation close to main interatrial conduction fascicles (P=0.035). Ablation of rotor domains (ablation line, 3.5±0.9 cm) effectively decreased the frequency of activation in both ipsilateral and contralateral atria (P<0.05 for both), whereas ablation of nonrotor domains did not. Acute conversion to sinus rhythm was observed in 2 patients after ablation of rotor domains. At 1-year follow-up, 70% remained in sinus rhythm (85% out-of-antiarrhythmic drugs). CONCLUSIONS: Rotor domains appropriately explain long-standing persistent atrial fibrillation physiology at its frequency content. Their ablation effectively modifies dynamics on restricted ablation.

Characterization of a stepwise approach in cavotricuspid isthmus ablation for typical atrial flutter: A randomized study comparing three catheters.

INTRODUCTION: Our aim was to characterize a stepwise approach in cavotricuspid isthmus ablation for typical atrial flutter in a prospective, noncrossover randomized study. METHODS: One hundred and fifty patients referred for cavotricuspid isthmus (CTI)-dependent atrial flutter ablation were randomized to undergo an ablation with an 8-mm-tip catheter (group 1), a 3.5-mm open irrigation-tip catheter (group 2), and a 3.5-mm open irrigation porous-tip catheter (group 3). A stepwise approach was performed, changing the ablation site from medial to septal aspects of the CTI, in case it was not effective without crossover between catheters. RESULTS: CTI block was achieved in all the patients using only one catheter. There was a 68% efficacy in group 1, 40% in group 2, and 28% in group 3 to achieve CTI block within 10 minutes (P  =  0.001) and 96%, 70%, and 70% in groups 1, 2, and 3, respectively, within 20 minutes (P  =  0.002) of radiofrequency ablation. The 8-mm catheter was also faster in fluoroscopy time and CTI block time. There were no differences in efficiency in the both irrigated catheters. There were no significant differences in complications among three catheters. CONCLUSIONS: With this stepwise approach, it is possible to achieve CTI block in all cases, using a single catheter without crossover, with good times of procedure and with a low complication rate. The 8-mm solid catheter is faster than the other irrigated-tip catheters. The 3.5-mm open irrigation porous-tip catheter is as effective and safe as the conventional irrigated-tip catheter.

Differential methylation of lncRNA KCNQ1OT1 promoter polymorphism was associated with symptomatic cardiac long QT.

AIM: To investigate whether the differential methylation of KCNQ1OT1 was associated with the risk of symptomatic long QTc. PATIENTS & METHODS: We investigated the methylation status of KCNQ1OT1 in a cohort of patients (n = 131) with a symptomatic prolonged QTc. All the patients were genotyped for a common promoter polymorphism (rs11023840). They were also genotyped for DNA digested with the methylation-sensitive HpaII restriction enzyme. RESULTS: We found a significant higher frequency of AA genotype (p = 0.02) in the patients compared with healthy controls (n = 240). In the HpaII-digested samples there was a higher frequency of the A-allele among the patients compared with the controls (p = 0.02). CONCLUSION: Our findings supported a role for the differential methylation/imprinting of KCNQ1OT1 in the risk for symptomatic prolonged QTc.

Aleteo auricular atípico y ablación de la conducción transauricular receptor-donante tras trasplante cardiaco ortotópico / Atypical atrial flutter and ablation of recipient-to-donor atrioatrial conduction after orthotopic heart transplant

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Momento del implante de un marcapasos tras el recambio valvular aórtico percutáneo / Timing of pacemaker implantation after percutaneous aortic valve replacement

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