Effect on nutritional status and biomarkers of inflammation and oxidation of an oral nutritional supplement (with or without probiotics) in malnourished hemodialysis patients. A multicenter randomized clinical trial "Renacare Trial".

Background: Malnutrition in patients undergoing hemodialysis is frequent and associated with a reduction in muscular mass and strength, with an increment in biomarkers of inflammation and oxidation. Materials and methods: Randomized, multicenter, parallel-group trial in malnourished hemodialysis patients with three groups [(1) control (C) individualized diet, (2) oral nutritional supplement-ONS- + placebo-SU- PL-, and (3) ONS + probiotics-SU-PR]; the trial was open regarding the intake of ONS or individualized diet recommendations, but double-blind for the intake of probiotics. We obtained, at baseline and after 3 and 6 months, anthropometric measurements, handgrip strength, bioelectrical impedance analysis (BIA), dietary records, and routine biochemical parameters. Inflammation and oxidation were determined using ELISA techniques (Versamax and ProcartaPlex multiplex Immunoassay). Results were analyzed by intention to treat. Results: A total of 31 patients (11 corresponding to group C, 10 to SU-PL, and 10 to SU-PR) completed the 6-months trial. The two groups that took supplements significantly increased their protein calorie, fat (total and n-3), and fiber intake. Weight and fat-free mass (FFM) also increased significantly in the groups on supplements, both at 3 and 6 months, and dynamometry did so in the SU-PL group. At month 3, prealbumin and vitamin D were significantly increased in the SU-TOT (SU-PL + SU-PR) group. No changes were observed regarding levels of phosphorus and potassium in any of the groups. Urea increased significantly at 6 months in the SU-PL group. There were significant changes in some inflammation biomarkers in the groups on supplements during the intervention (brain-derived neurotrophic factor, bone morphogenetic protein-2, MCP-1, IL-1-beta, IL-10, IL-4, and IL-8). The total antioxidant capacity (TAC) increased significantly in the supplemented patients, with no significant changes observed in isoprostanes. Conclusion: The specific ONS improved protein-calorie intake, nutritional status (mainly FFM), and some biomarkers of inflammation/oxidation. The addition of probiotics could have a synergistic effect with ONS in such biomarkers. Clinical trail registration: https://clinicaltrials.gov/ct2/show/, identifier NCT03924089.

Electrogram voltage and pacing threshold before ablation, measured by mini-electrodes, predict parameters indicative of transmural lesions in the human atrium.

PURPOSE: An important attenuation of the atrial signal recorded with mini-electrodes (ME) embedded in an 8-mm tip was associated with a transmural radiofrequency lesion. Our aim was to assess if parameters obtained from ME or conventional bipoles before applications predict successful atrial lesions. METHODS: We prospectively included 33 consecutive patients undergoing cavotricuspid isthmus (CTI) ablation. Electrogram voltages and pacing thresholds were measured with ME and conventional bipoles before and after radiofrequency (RF) applications. The time before the loss of capture during applications was recorded. Lesions were considered successful, in accordance with preclinical data, if ME voltage decreased > 54%. RESULTS: Of 207 applications, 107 could be analyzed. During applications, voltages decreased more in the ME than in the conventional bipoles (66.8 ± 26.1% vs 37.5 ± 42.5%, P = 0.001). Likewise, pacing threshold increased significantly more using the ME (86.3 ± 22.9% ME, 52.6 ± 35.6% conventional, P = 0.001). ME pre-ablation voltages were significantly higher and pacing thresholds significantly lower in successful lesions (voltage 0.88 ± 0.71 vs 0.26 ± 0.18 mV, P = 0.0001; threshold 1.6 ± 1.7 vs 2.8 ± 3.0, P = 0.04). Neither of these parameters with conventional bipoles nor time to loss of capture showed differences. A ME voltage > 0.33 mV and a pacing threshold < 1.5 mA predicted a successful lesion with 0.78 and 0.6 sensitivity and 0.78 and 0.59 specificity. CONCLUSIONS: Certain pre-ablation parameters derived from ME such as electrogram voltage and pacing threshold differ from those obtained by a conventional configuration and can predict a successful atrial lesion.

A constant postpacing interval in response to overdrive pacing with variable number of beats: An aid in the identification of entrainment for a particular pacing train during macroreentrant atrial tachycardias.

BACKGROUND: When pacing trains with a constant cycle length (CL) but increasing number of beats are introduced during a macroreentrant atrial tachycardia (MAT), the postpacing interval (PPI) is expected to increase if entrainment does not occur but could be stable if entrainment occurs. We tested the ability of PPI analysis to detect entrainment. METHODS: Synchronized pacing trains with increasing number of beats (1-20) were delivered from the coronary sinus (CS) and lateral right atrium (RA) at a CL 20 ms shorter than the MAT CL. Pacing trains were grouped in pairs differing by one-paced beat, and the ∆PPI measured. RESULTS: In an initial prospective cohort of 21 patients (48% had left atrial flutter) the mean ∆PPI was 21.3 ± 5.6 ms for pairs of pacing trains in which neither entrained the MAT and 2.8 ± 1.4 ms for those in which both entrained the MAT (P < .0001). Results were similar for common vs atypical flutter, PPI-TCL ≤30 ms vs PPI-TCL >30 ms, presence vs absence of antiarrhythmic drugs and faster vs slower MAT. When an index pacing train was compared to one with two-paced beats less, a PPI difference of <19 ms identified entrainment with 95% sensitivity and 98% specificity. In a validation cohort of 16 patients, this cut-off value resulted in sensitivity and specificity of 90% and 94%. CONCLUSIONS: A relatively constant ∆PPI in response to overdrive pacing with identical CL but different number of beats allows accurate discrimination between trains that entrained vs those which did not entrain a MAT.

Relationship between left atrium catheter contact force and pacing threshold.

PURPOSE: The purpose of this study is to analyze the relationship between contact force (CF) and pacing threshold in left atrium (LA). METHODS: Six to ten LA sites were studied in 28 consecutive patients with atrial fibrillation undergoing pulmonary vein isolation. Median CF, bipolar and unipolar electrogram voltage, impedance, and bipolar and unipolar thresholds for consistent constant capture and for consistent intermittent capture were measured at each site. RESULTS: Pacing threshold measurements were performed at 188 LA sites. Both unipolar and bipolar pacing thresholds correlated significantly with median CF; however, unipolar pacing threshold correlated better (unipolar: Pearson R -0.45; p < 0.001; Spearman Rho -0.62; p < 0.001, bipolar: Pearson R -0.39; p < 0.001; Spearman Rho -0.52; p < 0.001). Consistent constant capture threshold had better correlation with median CF than consistent intermittent capture threshold for both unipolar and bipolar pacing (Pearson R -0.45; p < 0.001 and Spearman Rho -0.62; p < 0.001 vs. Pearson R -0.35; p < 0.001; Spearman Rho -0.52; p < 0.001). The best pacing threshold cutoff point to detect a good CF (>10 g) was 3.25 mA for unipolar pacing with 69% specificity and 73% sensitivity. Both increased to 80% specificity and 74% sensitivity for sites with normal bipolar voltage and a pacing threshold cutoff value of 2.85 mA. CONCLUSIONS: Pacing thresholds correlate with CF in human not previously ablated LA. Since the combination of a normal bipolar voltage and a unipolar pacing threshold <2.85 mA provide reasonable parameters of validity, pacing threshold could be of interest as a surrogate for CF in LA.

Clinical impact of defibrillation testing at the time of implantable cardioverter-defibrillator insertion.

BACKGROUND: Ventricular fibrillation is routinely induced during implantable cardioverter-defibrillator insertion to assess defibrillator performance, but this strategy is experiencing a progressive decline. We aimed to assess the efficacy of defibrillator therapies and long-term outcome in a cohort of patients that underwent defibrillator implantation with and without defibrillation testing. METHODS: Retrospective observational series of consecutive patients undergoing initial defibrillator insertion or generator replacement. We registered spontaneous ventricular arrhythmias incidence and therapy efficacy, and mortality. RESULTS: A total of 545 patients underwent defibrillator implantation (111 with and 434 without defibrillation testing). After 19 (range 9-31) months of follow-up, the death rate per observation year (4% vs. 4%; p = 0.91) and the rate of patients with defibrillator-treated ventricular arrhythmic events per observation year (with test: 10% vs. without test: 12%; p = 0.46) were similar. The generalized estimating equations-adjusted first shock probability of success in patients with test (95%; CI 88-100%) vs. without test (98%; CI 96-100%; p = 0.42) and the proportion of successful antitachycardia therapies (with test: 87% vs. without test: 80%; p = 0.35) were similar between groups. There was no difference in the annualized rate of failed first shock per patient and per shocked patient between groups (5% vs. 4%; p = 0.94). CONCLUSIONS: In this observational study, that included an unselected population of patients with a defibrillator, no difference was found in overall mortality, first shock efficacy and rate of failed shocks regardless of whether defibrillation testing was performed or not.

Implantable defibrillator electrograms and origin of left ventricular impulses: an analysis of regionalization ability and visual spatial resolution.

INTRODUCTION: The implantable cardioverter-defibrillator (ICD) electrogram (EG) is a documentation of ventricular tachycardia. We prospectively analyzed EGs from ICD electrodes located at the right ventricle apex to establish (1) ability to regionalize origin of left ventricle (LV) impulses, and (2) spatial resolution to distinguish between paced sites. METHODS AND RESULTS: LV electro-anatomic maps were generated in 15 patients. ICD-EGs were recorded during pacing from 22 ± 10 LV sites. Voltage of far-field EG deflections (initial, peak, final) and time intervals between far-field and bipolar EGs were measured. Blinded visual analysis was used for spatial resolution. Initial deflections were more negative and initial/peak ratios were larger for lateral versus septal and superior versus inferior sites. Time intervals were shorter for apical versus basal and septal versus lateral sites. Best predictive cutoff values were voltage of initial deflection <-1.24 mV, and initial/peak ratio >0.45 for a lateral site, voltage of final deflection <-0.30 for an inferior site, and time interval <80 milliseconds for an apical site. In a subsequent group of 9 patients, these values predicted correctly paced site location in 54-75% and tachycardia exit site in 60-100%. Recognition of paced sites as different by EG inspection was 91% accurate. Sensitivity increased with distance (0.96 if ≥ 2 cm vs 0.84 if < 2 cm, P < 0.001) and with presence of low-voltage tissue between sites (0.94 vs 0.88, P < 0.001). CONCLUSIONS: Standard ICD-EG analysis can help regionalize LV sites of impulse formation. It can accurately distinguish between 2 sites of impulse formation if they are ≥2 cm apart.

Utilidad diagnóstica de los electrogramas almacenados por el desfibrilador automático implantable / Diagnostic usefulness of the electrograms stored by implantable cardioverter–defibrillators

Los electrogramas almacenados por los desfibriladores implantables actuales permiten al clínico revisar las alteraciones eléctricas durante los eventos que conducen a la activación del desfibrilador, así como evaluar el resultado de la terapia administrada. En la mayoría de los pacientes, esta información permite efectuar un diagnóstico preciso del tipo de arritmia causante de la activación del dispositivo y, como resultado, optimizar el tratamiento de estos pacientes. Sin embargo, todavía es preciso establecer criterios de discriminación adicionales que nos permitan diferenciar con mayor precisión la etiología de los episodios detectados por el dispositivo. En este artículo se describen: a) los principios básicos para la discriminación de arritmias basado en el análisis del registro de los electrogramas intracavitarios (EGM) de los episodios; b) la utilidad del análisis de los EGM en el tratamiento de pacientes con arritmias ventriculares; c) las principales limitaciones de los métodos empleados, y d) finalmente, se presentan pruebas científicas de la utilidad de nuevos métodos de discriminación (AU)

The electrograms stored by present-day implantable cardioverter–defibrillators (ICDs) enable clinicians to review the electrical changes that occur during events leading to device discharge and to evaluate the effects of the therapy administered. In most patients, this information enables the type of arrhythmia responsible for ICD activation to be accurately determined and, consequently, treatment to be optimized. Nevertheless, additional discriminative criteria are needed to enable the etiology of the episodes detected by the device to be classified yet more accurately. This article considers: a) the basic principles for classifying arrhythmias on the basis of an analysis of stored intracardiac electrograms of arrhythmic episodes; b) the usefulness of intracardiac electrogram analysis for treating patients with ventricular arrhythmias; c) the main limitations of the classification methods currently used; and, finally, d) the evidence available on the usefulness of new classification methods (AU)

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 < or =0.2 mV. Electrograms with > or =2 components were recorded more frequently at the inner than at the entrance of CCs (100% versus 75%, P< or =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< or =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.

Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease.

OBJECTIVES: We sought to evaluate the feasibility of identifying and ablating the substrate of unmappable ventricular tachycardia (VT). BACKGROUND: Noninducible and nonstable VT cannot be ablated by the conventional approach. METHODS: We studied 24 patients with documented monomorphic VT. Twenty-one patients had ischemic cardiomyopathy, two had nonischemic cardiomyopathy, and one had tetralogy of Fallot. Twelve patients had an implantable cardioverter-defibrillator. Conventional activation mapping was not possible in 18 patients: at least 1 of the clinical VTs or the clinical VT was not inducible in 12 patients, and VT was not tolerated in 6 patients. This group had experienced between 1 and 106 VT episodes in the month before the ablation procedure. Endocardial electroanatomic activation maps (Carto System) during sinus rhythm (SR) and right ventricular apex (RVA) pacing were obtained to define areas for which an electrogram displayed isolated, delayed components (E-IDC). These electrograms were characterized by double or multiple components separated by >/=50 ms. RESULTS: One area of E-IDC was recorded in 20 patients, and 2 or more were recorded in 4 patients. In 23 patients, these areas were detected during RVA pacing; in only 14 during SR. An E-IDC area related to the clinical VT was identified in each patient. Ablation guided by E-IDC suppressed all but one clinical VT whose inducibility suppression was tested. During a follow-up period of 9 +/- 4 months, three patients had recurrences of the ablated VT and two of a different VT. CONCLUSIONS: Electrograms with IDCs related to clinical VT can be identified in the majority of patients during RVA pacing. Radiofrequency ablation of E-IDC seems effective in controlling unmappable VT.

Usefulness of paced activation sequence mapping in catheter ablation of accessory pathways.

INTRODUCTION: Radiofrequency (RF) ablation of accessory pathways (APs) is often a time-consuming procedure, mainly because conventional criteria have modest accuracy. Thus, additional mapping criteria are desirable. Our hypothesis was that comparison of paced atrial activation sequences with that obtained during orthodromic AV reentrant tachycardia might be useful for locating the atrial insertion of single APs. METHODS AND RESULTS: The study included 15 patients with a single AP referred for ablation. Analysis of the atrial activation sequence was simplified by measuring the activation time (AT) that elapsed between two atrial reference points placed next to the AV annulus on either side of the area containing the AP. Ablation was guided by conventional criteria. Before each RF delivery, a short pacing train was delivered from the ablation catheter and, after verification of atrial capture, the AT was compared with the AT obtained during orthodromic tachycardia. Fifty sites of RF delivery were appropriate for analysis. The multivariate model with the highest predictive power included a deviation of AT between pacing and tachycardia < or = 5 msec (P < 0.001), a local AV ratio > or = 1 (P = 0.04), and stability of the local electrogram (P = 0.05). The combination of all these criteria predicted a successful application with high sensitivity, specificity, and positive predictive value (92%, 86%, and 71% respectively). To validate the method prospectively, 10 additional consecutive patients underwent an AP ablation procedure guided by these criteria. CONCLUSION: This technique seems to be highly accurate in selecting the atrial site for RF ablation of single APs.