Silvia Castillo

Tachycardia-Related Channel in the Scar Tissue in Patients With Sustained Monomorphic Ventricular Tachycardias Influence of the Voltage Scar Definition

Background—Endocardial mapping before sustained monomorphic ventricular tachycardia (SMVT) induction may reduce mapping time during tachycardia and facilitate the ablation of unmappable VT. Methods and Results—Left ventricular electroanatomic voltage maps obtained during right ventricular apex pacing in 26 patients with chronic myocardial infarction referred for VT ablation were analyzed to identify conducting channels (CCs) inside the scar tissue. A CC was defined by the presence of a corridor of consecutive electrograms differentiated by higher voltage amplitude than the surrounding area. The effect of different levels of voltage scar definition, from 0.5 to 0.1 mV, was analyzed. Twenty-three channels were identified in 20 patients. The majority of CCs were identified when the voltage scar definition was ≤0.2 mV. Electrograms with ≥2 components were recorded more frequently at the inner than at the entrance of CCs (100% versus 75%, P≤0.01). The activation time of the latest component was longer at the inner than at the entrance of CCs (200±40 versus 164±53 ms, P≤0.001). Pacing from these CCs gave rise to a long-stimulus QRS interval (110±49 ms). Radiofrequency lesion applied to CCs suppressed the inducibility in 88% of CC-related tachycardias. During a follow-up of 17±11 months, 23% of the patients experienced a VT recurrence. Conclusions—CCs represent areas of slow conduction that can be identified in 75% of patients with SMVT. A tiered decreasing-voltage definition of the scar is critical for CC identification.

Combined evaluation of bedside clinical variables and the electrocardiogram for the differential diagnosis of paroxysmal atrioventricular reciprocating tachycardias in patients without pre-excitation.

OBJECTIVES The aim of this study was to assess the independent predictive contribution to the electrocardiogram (ECG) of bedside clinical variables to distinguish the major forms of paroxysmal supraventricular tachycardias. BACKGROUND Atrioventricular nodal re-entrant tachycardias (AVNRTs) and orthodromic reciprocating tachycardias (ORTs), through concealed accessory pathways, are major mechanisms of paroxysmal atrioventricular re-entrant tachycardias. METHODS We prospectively included 370 consecutive patients undergoing an electrophysiologic study for paroxysmal, regular, narrow-QRS complex tachycardias without pre-excitation in sinus rhythm. A diagnostic interpretation of ECG recordings was performed by 2 observers blinded to invasive diagnosis used as gold standard. The independent diagnostic contribution of basic clinical variables from a 7-item questionnaire was analyzed alone and in combination with the ECG interpretation by stepwise logistic regression. RESULTS AVNRTs and ORTs were demonstrated in 262 and 108 patients, respectively. Age at symptom onset (odds ratio [OR]: 1.27), presence of palpitations in the neck (OR: 3.54), and female sex (OR: 2.96) (all p = 0.0001) were the clinical variables with significant diagnostic power for AVNRT diagnosis. These variables were selected by the logistic model as predictors of the tachycardia diagnosis when the ECG interpretation was included in the analysis (C statistic = 0.81 vs. 0.75 with clinical variables alone; p = 0.003). Neck palpitation was the only predictor of AVNRT when positive ECG findings were lacking. CONCLUSIONS Age at the onset of symptoms, sensation of rapid regular pounding in the neck during tachycardia, and female sex are the only significant clinical variables in the differential diagnosis of paroxysmal atrioventricular reciprocating tachycardias in patients without pre-excitation in sinus rhythm. Their consideration adds significant diagnostic information to the ECG.

Decreased glutathione and low catalase activity contribute to oxidative stress in children with α-1 antitrypsin deficiency

Background Recent investigations in animal models have revealed oxidative stress and oxidative damage in the pathogenesis of alpha-1 antitrypsin deficiency (AATD). However, no data are available on the oxidative stress status and antioxidant enzyme activity in these patients. This study was aimed to analyse the oxidative stress profile and enzymatic antioxidant defence mechanisms in children with AATD. Methods Oxidative stress parameters and the activity of the main antioxidant enzymes were prospectively measured in serum of fifty-one children diagnosed with AATD and thirty-eight control individuals. Results Oxidative stress was increased in the serum of children with intermediate- (MZ; SZ) and high-risk (ZZ) phenotypes for developing AATD-related emphysema and/or liver disease. When compared with the control group, intermediate- and high-risk groups showed significantly lower total glutathione and reduced glutathione levels, decreased catalase activity and increased glutathione peroxidase activity leading to an accumulation of hydrogen peroxide that would explain the significantly increased levels of oxidative stress biomarkers observed in these patients. No differences were observed between the control (MM) and the low-risk (MS; SS) groups. A gradation in oxidative stress parameters was observed when patients were compared among themselves, in that the expression of the Z allele produces a higher oxidative stress status in homozygous (ZZ) than in heterozygous (MZ; SZ) patients. Conclusions Increased oxidative stress, together with reduced antioxidant defence are involved in the pathophysiology of AATD at early stages, opening up a new rationale for the use of antioxidant therapies in the treatment of the disease.

Diastolic Dysfunction Following Anthracycline-Based Chemotherapy in Breast Cancer Patients: Incidence and Predictors

INTRODUCTION Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data from longitudinal studies of diastolic dysfunction (DD) in this group of patients are scarce. The objective of the present study was to assess the incidence, evolution, and predictors of DD in patients with breast cancer treated with anthracyclines. METHODS This analytical, observational cohort study comprised 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) for breast cancer. All patients underwent clinical evaluation, echocardiogram, and measurement of cardiac biomarkers at baseline, end of anthracycline-based CHT, and at 3 months and 9 months after anthracycline-based CHT was completed. Fifteen patients receiving trastuzumab were followed with two additional visits at 6 and 12 months after the last dose of anthracycline-based CHT. A multivariate analysis was performed to find variables related to the development of DD. Fifteen of the 100 patients had baseline DD and were excluded from this analysis. RESULTS At the end of follow-up (median: 12 months, interquartile range: 11.1-12.8), 49 patients (57.6%) developed DD. DD was persistent in 36 (73%) but reversible in the remaining 13 patients (27%). Four patients developed cardiotoxicity (three patients had left ventricular systolic dysfunction and one suffered a sudden cardiac death). None of the patients with normal diastolic function developed systolic dysfunction during follow-up. In the logistic regression model, body mass index (BMI) and age were independently related to the development of DD, with the following odds ratio values: BMI: 1.19 (95% confidence interval [CI]: 1.04-1.36), and age: 1.12 (95% CI: 1.03-1.19). Neither cardiac biomarkers nor remaining clinical variables were predictors of DD. CONCLUSION Development of diastolic dysfunction after treatment with anthracycline or anthracycline- plus trastuzumab chemotherapy is common. BMI and age were independently associated with DD following anthracycline chemotherapy.

La cartografía electroanatómica no fluoroscópica (sistema CARTO) en la ablación de las taquicardias auriculares

Introduccion y objetivos La introduccion de los sistemas navegadores ha supuesto un cambio sustancial en la cartografia electrofisiologica cardiaca. Presentamos nuestra experiencia con el uso de la cartografia electroanatomica no fluoroscopica en pacientes con taquicardias auriculares. Pacientes y metodo Se incluye a 24 pacientes consecutivos con taquicardias auriculares (10 de ellos con intentos previos de ablacion fallidos). En todos los casos se realizo una cartografia auricular electroanatomica mediante el sistema CARTO, que combina informacion electrofisiologica y espacial y permite la visualizacion de la activacion atrial en una reconstruccion anatomica tridimensional de la auricula. La cartografia se realizo durante taquicardia (22 pacientes) o en ritmo sinusal (2 pacientes), con abordaje en la auricula izquierda en 12 pacientes. La ablacion se efectuo con un cateter de punta irrigada en 3 pacientes. Resultados La cartografia tridimensional permitio una clara y rapida distincion entre un mecanismo macrorreentrante (9 pacientes) y un origen focal (15 pacientes). Las aplicaciones de radiofrecuencia se dirigieron hacia el istmo critico de conduccion identificado en las macrorreentradas mediante mapas de voltaje de auriculogramas o hacia el area de mayor precocidad ectopica focal en los mapas de activacion. El tratamiento se realizo con exito en 19 pacientes (79,2%) y se produjo una recurrencia precoz en 2 de ellos. El tiempo de fluoroscopia fue de 60 ± 21 min. Conclusiones La cartografia electroanatomica con sistema CARTO permitio la visualizacion tridimensional de la activacion auricular, evitando el esfuerzo de integracion electrofisiologico y anatomico en estos pacientes con taquicardias auriculares. El apoyo iconografico que supone podria facilitar el exito de la ablacion con radiofrecuencia en este seleccionado grupo de pacientes.

Accelerated telomere attrition in children and teenagers with α1-antitrypsin deficiency

Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of α1-antitrypsin deficiency (AATD), we hypothesised that telomere shortening would be accelerated in AATD patients. This study aimed to assess telomere length in AATD patients and to study its association with α1-antitrypsin phenotypes. Telomere length, telomerase activity, telomerase reverse transcriptase (hTERT) expression and biomarkers of oxidative stress were measured in 62 children and teenagers (aged 2–18 years) diagnosed with AATD and 18 controls (aged 3–16 years). Our results show that intermediate-risk (MZ; SZ) and high-risk (ZZ) AATD patients have significantly shorter telomeres and increased oxidative stress than controls. Correlation studies indicate that telomere length was related to oxidative stress markers in AATD patients. Multiple hypothesis testing revealed an association between telomere length, telomerase activity, hTERT expression and AATD phenotypes; high-risk patients showed shorter telomeres, lower hTERT expression and decreased telomerase activity than intermediate-risk and low-risk patients. AATD patients show evidence of increased oxidative stress leading to telomere attrition. An association between telomere and α1-antitrypsin phenotypes is observed suggesting that telomere length could be a promising biomarker for AATD disease progression. Patients with α1-antitrypsin deficiency have shorter telomeres than healthy individuals http://ow.ly/8NHS300zz5A

Antibiotic resistance and population structure of cystic fibrosis Pseudomonas aeruginosa isolates from a Spanish multi-centre study

The first Spanish multi-centre study on the microbiology of cystic fibrosis (CF) was conducted from 2013 to 2014. The study involved 24 CF units from 17 hospitals, and recruited 341 patients. The aim of this study was to characterise Pseudomonas aeruginosa isolates, 79 of which were recovered from 75 (22%) patients. The study determined the population structure, antibiotic susceptibility profile and genetic background of the strains. Fifty-five percent of the isolates were multi-drug-resistant, and 16% were extensively-drug-resistant. Defective mutS and mutL genes were observed in mutator isolates (15.2%). Considerable genetic diversity was observed by pulsed-field gel electrophoresis (70 patterns) and multi-locus sequence typing (72 sequence types). International epidemic clones were not detected. Fifty-one new and 14 previously described array tube (AT) genotypes were detected by AT technology. This study found a genetically unrelated and highly diverse CF P. aeruginosa population in Spain, not represented by the epidemic clones widely distributed across Europe, with multiple combinations of virulence factors and high antimicrobial resistance rates (except for colistin).

Bronchopulmonary infection–colonization patterns in Spanish cystic fibrosis patients: Results from a national multicenter study

BACKGROUND Clinical and demographical knowledge on Spanish cystic fibrosis (CF) patients is incomplete as no national registry exists. CF-microbiology has not been studied at national level. The results of the first Spanish multicenter study on CF microbiology are presented. METHODS 24 CF-Units for adult (n=12) and pediatric (n=12) patients from 17 hospitals provided sputa and clinical data from 15 consecutive patients. Cultures and susceptibility testing were performed. Colonization impact on pulmonary function was assessed. RESULTS 341 patients [mean (SD) age 21 (11) years, 180≥18years, mean (SD) FEV1=68 (25)%] were included. Pseudomonas aeruginosa was reported as chronic, intermittent or absent in 46%, 22% and 32% of patients, respectively. The annual prevalence was 62%. Positive P. aeruginosa and methicillin-resistant Staphylococcus aureus cultures were significantly associated with lower FEV1 (p<0.001 and p=0.003, respectively). CONCLUSIONS The representative subset of the Spanish CF-population which has been clinically, demographically and microbiologically characterized will serve as a reference for future CF studies in Spain.

Non-Fluoroscopic Electroanatomical Mapping (CARTO System) in the Ablation of Atrial Tachycardias

INTRODUCTION AND OBJECTIVES The recent introduction of navigation systems has made substantial improvements in cardiac electrophysiological mapping. We present our experience with non-fluoroscopic electroanatomical mapping in patients with atrial tachycardias. PATIENTS AND METHOD We studied 24 consecutive patients with atrial tachycardias (10 of whom had undergone previous radiofrequency ablation which failed). In all patients we performed electroanatomical mapping of the atria with the CARTO system, which combines electrophysiological and spatial information and allows visualization of atrial activation in a three-dimensional anatomical reconstruction of the atrial cavity. Mapping was performed during tachycardia (22 patients) or in sinus rhythm (2 patients), using a left atrial approach in 12 patients. Cooled-tip ablation was performed in 3 patients. RESULTS Three-dimensional mapping distinguished clearly and rapidly between reentrant (9 patients) and focal mechanisms (15 patients). Radiofrequency catheter ablation was aimed at the critical isthmus of conduction (voltage maps) in patients with macroreentrant tachycardias. For focal tachycardias the catheter was re-navigated within the target area (activation maps) to the earliest focus of ectopic impulses. Acute success was obtained in 19 patients (79.2%), with early recurrence in 2 of them. Fluoroscopy time was 60 (21 min). CONCLUSIONS Visualization of atrial activation in a three-dimensional reconstruction of the atria with the CARTO electroanatomical mapping system facilitated the integration of electrophysiological and anatomical information in patients with atrial tachycardias. This technique is potentially helpful in ensuring successful treatment of the substrate of tachycardia in this selected group of patients.

Fibrilación auricular en la mujer: análisis de la situación en España

La fibrilacion auricular es la arritmia sostenida mas frecuente en la poblacion general y tiene un gran impacto en la morbimortalidad de personas de edad avanzada. La mayor parte de los datos sobre epidemiologia de la fibrilacion auricular procede de poblaciones norteamericanas, especialmente del estudio de Framingham, y no hay datos generales en Espana. Algunos estudios encuentran cifras de prevalencia de fibrilacion auricular en Espana entre el 2 y el 17%, dependiendo de la edad y el ambito de estudio. En algunos de ellos se senalan tambien las distintas prevalencias en mujeres y varones, pero no existen datos fiables sobre este aspecto en nuestro pais. Dada la importancia creciente de esta arritmia y sus repercusiones pronosticas, parece necesario realizar estudios especificamente dirigidos a conocer su situacion real en Espana, tanto en general como diferenciada por sexos.