Mejoría clínica, hemodinámica y de marcadores bioquímicos tras estimulación ventricular desde el área de la rama izquierda / Clinical, hemodynamic and biochemical improvement related to left bundle branch area pacing

Resumen Introducción: La estimulación ventricular derecha puede provocar insuficiencia cardiaca y disfunción ventricular. La estimulación en el área de la rama izquierda (ERI) permite capturar el sistema His-Purkinje. La ERI se ha estudiado en la estimulación ventricular y en la terapia de resincronización cardiaca. La evolución de los péptidos natriuréticos (NT-proBNP) asociada a la ERI no ha sido estudiada hasta el momento. Métodos: Se incluyeron pacientes consecutivos remitidos para implante de marcapasos o terapia de resincronización cardiaca. El implante del electrodo de ERI se realizó siguiendo la técnica descrita por Huang et al. Los pacientes eran sometidos a ecocardiograma y determinación de NT-proBNP antes y cuatro semanas después del procedimiento. Resultados: Se analizaron 50 pacientes con implante exitoso y seguimiento completo. No hubo diferencias significativas entre los umbrales medidos durante el procedimiento y los obtenidos al cabo de 12 semanas. La ERI logró una reducción significativa de la anchura del complejo QRS (148 ± 21 vs. 107 ± 11 ms; p = 0.029). La ERI logró una reducción significativa de la clasificación funcional en el conjunto de la muestra y una reducción significativa de NT-proBNP (2,888.2 ± 510 vs. 1,181 ± 130 pg/ml; p = 0.04). En pacientes con fracción de eyección del ventrículo izquierdo (FEVI) < 50% y asincronía se logró un incremento significativo de la FEVI con la ERI (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). Conclusiones: La ERI es factible en la mayoría de pacientes y se asocia con una reducción de la duración del complejo QRS. La ERI no condiciona un efecto deletéreo sobre la FEVI a corto-medio plazo; además, en aquellos pacientes con FEVI deprimida y asincronía ventricular permite incrementar la FEVI.

Abstract Background: Right ventricular pacing is associated with risk of heart failure and left ventricular dysfunction. Left bundle branch area pacing (LBBP) has emerged as an alternative method for delivering physiological pacing. The effect of LBBP on N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been investigated. Method: Finally, 50 patients referred for pacemaker implantation were included. LBBP was performed as described previously by Huang et al. Transthoracic echocardiogram and NT-proBNP were performed before and four weeks after the procedure. Results: 50 patients were analyzed. There were not differences between ventricular thresholds during the procedure and 3 months later, LBBP significantly reduced QRS complex duration (148 ± 21 vs. 107 ± 11 ms; p = 0.029). LBBP significantly improved NYHA functional class and reduced NT-proBNP concentration (2888.2 ± 510 vs. 1181 ± 130 pg/ml; p = 0.04). In patients showing left ventricular ejection fraction (LVEF) < 50% and ventricular desynchrony LBBP showed a significant LVEF increase (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). Conclusions: LBBP was feasible and safe in most of patients. LBBP was associated with reduction in QRS width and with increase in LVEF in patients with ventricular desynchrony, while in patients with normal LVEF it remained unchanged during follow-up.

Clinical, hemodynamic and biochemical improvement related to left bundle branch area pacing.

BACKGROUND: Right ventricular pacing is associated with risk of heart failure and left ventricular dysfunction. Left bundle branch area pacing (LBBP) has emerged as an alternative method for delivering physiological pacing. The effect of LBBP on N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been investigated. METHOD: Finally, 50 patients referred for pacemaker implantation were included. LBBP was performed as described previously by Huang et al. Transthoracic echocardiogram and NT-proBNP were performed before and four weeks after the procedure. RESULTS: 50 patients were analyzed. There were not differences between ventricular thresholds during the procedure and 3 months later, LBBP significantly reduced QRS complex duration (148 ± 21 vs. 107 ± 11 ms; p = 0.029). LBBP significantly improved NYHA functional class and reduced NT-proBNP concentration (2888.2 ± 510 vs. 1181 ± 130 pg/ml; p = 0.04). In patients showing left ventricular ejection fraction (LVEF) < 50% and ventricular desynchrony LBBP showed a significant LVEF increase (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). CONCLUSIONS: LBBP was feasible and safe in most of patients. LBBP was associated with reduction in QRS width and with increase in LVEF in patients with ventricular desynchrony, while in patients with normal LVEF it remained unchanged during follow-up.

INTRODUCCIÓN: La estimulación ventricular derecha puede provocar insuficiencia cardiaca y disfunción ventricular. La estimulación en el área de la rama izquierda (ERI) permite capturar el sistema His-Purkinje. La ERI se ha estudiado en la estimulación ventricular y en la terapia de resincronización cardiaca. La evolución de los péptidos natriuréticos (NT-proBNP) asociada a la ERI no ha sido estudiada hasta el momento. MÉTODOS: Se incluyeron pacientes consecutivos remitidos para implante de marcapasos o terapia de resincronización cardiaca. El implante del electrodo de ERI se realizó siguiendo la técnica descrita por Huang et al. Los pacientes eran sometidos a ecocardiograma y determinación de NT-proBNP antes y cuatro semanas después del procedimiento. RESULTADOS: Se analizaron 50 pacientes con implante exitoso y seguimiento completo. No hubo diferencias significativas entre los umbrales medidos durante el procedimiento y los obtenidos al cabo de 12 semanas. La ERI logró una reducción significativa de la anchura del complejo QRS (148 ± 21 vs. 107 ± 11 ms; p = 0.029). La ERI logró una reducción significativa de la clasificación funcional en el conjunto de la muestra y una reducción significativa de NT-proBNP (2,888.2 ± 510 vs. 1,181 ± 130 pg/ml; p = 0.04). En pacientes con fracción de eyección del ventrículo izquierdo (FEVI) < 50% y asincronía se logró un incremento significativo de la FEVI con la ERI (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). CONCLUSIONES: La ERI es factible en la mayoría de pacientes y se asocia con una reducción de la duración del complejo QRS. La ERI no condiciona un efecto deletéreo sobre la FEVI a corto-medio plazo; además, en aquellos pacientes con FEVI deprimida y asincronía ventricular permite incrementar la FEVI.

MIBG Therapy for Neuroblastoma: Precision Achieved With Dosimetry, and Concern for False Responders.

Neuroblastoma causes 15% of cancer mortality in children. High risk neuroblastoma has poor prognosis, with high relapse rate and mortality despite multimodal treatment. 123-I-meta-iodo-benzyl-guanidine (mIBG) scintigraphy is one of the current standard diagnostic procedures in neuroblastoma. mIBG can also be used therapeutically, labeled with 131-I, as a radiopharmaceutical agent, delivering targeted radiotherapy to tumoral sites. But published data of this strategy show heterogeneous results. One concern is that in most reports the infused activity is only based in body-weight, which could lead to infra or over-treatment, depending on inter-patient variability in radiation absorption. Activity adjustment by whole-body dosimetry can be used to homogeneize the treatment. Also, mIBG avid tumors may lose avidness along the treatment. As mIBG is used both for treatment and response evaluation, this could result in undetected progressions in patients with apparent complete response. We present a retrospective single-center review of neuroblastoma patients who received therapeutic 131-I-mIBG, focusing on cases with dosimetry-adjusted activity. Dosimetry allowed for a more precise delivery of radiation, reducing 81.1% of deviation from absorption target of 4 Gray (Gy), from 23.4% (±0.936 Gy) to 4.4% (± 0.176 Gy). Patients who showed partial or complete response had better and longer survival. Relapse/progression in non-responders was an early event (within 3 months from treatment). We also present one case of progression with apparent complete response due to loss of mIBG avidness, detected in our series.

Tests to Measure Core Stability in Laboratory and Field Settings: Reliability and Correlation Analyses.

Although core stability (CS) has been assessed through many different tests, the relationships among them are currently unknown. The main objective was to analyze the relationship between 5 representative tests used to assess CS in: (1) laboratory settings: Sudden Loading Test (SLT) and Stable and Unstable Sitting Test (SUST) and (2) field settings: Biering-Sørensen Test (BST), 3-Plane Core Strength Test, and Double-Leg Lowering Test. The reliability of these tests was also examined. In total, 33 recreationally active males performed the tests twice. The relationship between all variables was examined using Pearson correlation coefficient in those variables with a good reliability. Only stiffness and angular displacement in the SLT, dynamic unstable tasks in the SUST, and the holding time in the BST showed good reliability (intraclass correlation coefficient: .63-.91, typical error: 9.8%-21.0%). Few and low correlations were observed between the SLT, SUST, and BST. Despite finding several significant correlations among the dynamic unstable tasks of the SUST (r ≥ .807, P < .01), no correlations were found between the loading directions of the SLT. The absence of correlations between these tests suggests that CS measurements are not generalizable, as they probably assess different dimensions of CS, or in the case of the BST, a different capacity (ie, trunk extensor endurance).

Evaluation of a near-zero fluoroscopic approach for catheter ablation in patients with congenital heart disease.

PURPOSE: Radiation exposure (RE) is a matter of concern for patients with congenital heart disease (CHD) who not infrequently need multiple interventional procedures under fluoroscopy guidance. We sought to evaluate the safety and feasibility of a minimally fluoroscopic approach in patients with CHD undergoing catheter ablation using a new image integration module (IIM). METHODS: Consecutive patients with CHD undergoing catheter ablation using the Carto Univu™ IIM were included. A near-zero fluoroscopy procedure was defined by an effective dose (ED) ≤ 1 mSv. RE parameters (total fluoroscopy time [TFT], total dose area product [tDAP], and ED), ablation outcomes, and complications were evaluated. RESULTS: Fifty-five patients with CHD underwent 63 ablation procedures (supraventricular tachycardia, n = 53; ventricular tachycardia, n = 10). The CHD was simple in 25%, moderate in 42%, and complex in 33%. The use of the IIM resulted in very low levels of RE (median TFT 0.13 min [IQR 0-1.04], median tDAP 54.5 cGy cm2 [IQR 9.5-176.4], median ED 0.136 mSv [IQR 0.02-0.49]). Patients with complex CHD had significantly higher RE when compared with patients with simple and moderate defects. A total of 56/63 ablation procedures (89%) were performed with an ED ≤ 1 mSv. One patient developed sinus node dysfunction requiring pacemaker implantation. CONCLUSIONS: The use of a minimally fluoroscopic approach was safe and feasible resulting in very low RE during catheter ablation of patients with CHD. A near-zero fluoroscopy ablation was possible in up to 89% of the procedures.

Reliability of the Star Excursion Balance Test and Two New Similar Protocols to Measure Trunk Postural Control.

BACKGROUND: Although the Star Excursion Balance test (SEBT) has shown a good intrasession reliability, the intersession reliability of this test has not been deeply studied. Furthermore, there is an evident high influence of the lower limbs in the performance of the SEBT, so even if it has been used to measure core stability, it is possibly not the most suitable measurement. OBJECTIVE: (1) To assess the absolute and relative between-session reliability of the SEBT and 2 novel variations of this test to assess trunk postural control while sitting, ie, the Star Excursion Sitting Test (SEST) and the Star Excursion Timing Test (SETT); and (2) to analyze the relationships between these 3 test scores. DESIGN: Correlational and reliability test-retest study. SETTING: Controlled laboratory environment. PARTICIPANTS: Twenty-seven physically active men (age: 24.54 ± 3.05 years). METHOD: Relative and absolute reliability of the SEBT, SEST, and SETT were calculated through the intraclass correlation coefficient (ICC) and standard error of measurement (SEM), respectively. A Pearson correlation analysis was carried out between the variables of the 3 tests. MAIN OUTCOME MEASURES: Maximum normalized reach distances were assessed for different SEBT and SEST directions. In addition, composite indexes were calculated for SEBT, SEST, and SETT. RESULTS: The SEBT (dominant leg: ICC = 0.87 [0.73-0.94], SEM = 2.12 [1.66-2.93]; nondominant leg: ICC = 0.74 [0.50-0.87], SEM = 3.23 [2.54-4.45]), SEST (ICC = 0.85 [0.68-0.92], SEM = 1.27 [1.03-1.80]), and SETT (ICC = 0.61 [0.30-0.80], SEM = 2.31 [1.82-3.17]) composite indexes showed moderate-to-high 1-month reliability. A learning effect was detected for some SEBT and SEST directions and for SEST and SETT composite indexes. No significant correlations were found between SEBT and its 2 variations (r ≤ .366; P > .05). A significant correlation was found between the SEST and SETT composite indexes (r = .520; P > .01). CONCLUSIONS: SEBT, SEST, and SETT are reliable field protocols to measure postural control. However, whereas the SEBT assesses postural control in single-leg stance, SEST and SETT provide trunk postural control measures with lower influence of the lower-limbs. LEVEL OF EVIDENCE: III.

Is Viewing Sexually Explicit Material Cheating on Your Partner? A Comparison Between the United States and Spain.

This cross-sectional study examined whether university students from the U.S. (n = 392) and Spain (n = 200) considered the viewing of sexually explicit material (SEM) to be tantamount to committing infidelity. Participants' ages ranged from 18 to 36 (U.S. sample) and 18 to 35 (Spain sample), respectively. At both universities, the study was made available to students via a computer program that allows recruitment and completion of the questionnaires online. It was found that the majority of U.S. and Spanish participants (73 and 77%, respectively) indicated that they did not consider viewing SEM as an act of infidelity. Also, overall, U.S. participants, those who were not currently in a relationship, and those who do not view SEM, were significantly more likely to believe that viewing SEM constituted infidelity compared to Spanish participants, those currently in a relationship, and those who view SEM. Finally, it was found that among U.S. and Spanish participants, intolerance of infidelity in general, negative attitudes toward SEM, and the proclivity for jealousy significantly correlated with believing that viewing SEM was tantamount to infidelity. For U.S. participants only, religiosity and (low) self-esteem also correlated with the belief that viewing SEM was infidelity. Implications of the findings are discussed.

Reliability assessment and correlation analysis of 3 protocols to measure trunk muscle strength and endurance.

Different methods have been developed to quantify trunk muscle strength and endurance. However, some important protocol characteristics are still unclear, hindering the selection of the most suitable tests in each specific situation. The aim of this study was to examine the reliability and the relationship between 3 representative tests of the most common type of protocols used to assess trunk muscle strength and endurance. Twenty-seven healthy men performed each test twice spaced 1 month apart.Trunk strength and endurance were evaluated with an isokinetic dynamometer and 2 field tests including Biering-Sørensen test and Flexion-rotation trunk test. All tests showed a good relative consistency (intraclass correlation coefficient [ICC]> 0.75), except for the isokinetic endurance variables which had low-moderate reliability (0.37 < ICC > 0.65). Absolute reliability seemed slightly better in the isokinetic protocol than in the field tests, which showed about 12% of test-retest score increase. No significant correlations were found between test scores. After a familiarisation period for the field tests, the 3 protocols can be used to obtain reliable measures of trunk muscle strength and endurance. Based on the correlation analysis, these measures are not related, which highlights the importance of selecting the most suitable trunk test for each situation.

Dynamic trunk muscle endurance profile in adolescents aged 14-18: Normative values for age and gender differences.

BACKGROUND: The selection and validation of age- and gender-specific criterion-referenced cut-points for abdominal endurance are still unclear. OBJECTIVE: To stablish normative values for abdominal endurance in adolescents by age and gender using the Bench Trunk Curl-up Test (BTC). Additionally, the reliability of the BTC was analyzed. METHODS: Two hundred and sixteen untrained high school students (104 males - 112 females) were grouped into five age strata. Participants performed the BTC twice with a rest period of 72 h. Descriptive statistics and percentile scores were determined for each gender/age strata. RESULTS: Males showed higher BTC scores than females (males: 90.07 ± 32.65 repetitions; females: 73.43 ± 27.74 repetitions), but no significant differences between age strata nor age * gender interaction were found. Significant differences for the BTC scores between sessions were found (T1 = 72.06 ± 26.28 repetitions; T2 = 81.44 ± 31.27 repetitions). The ICC was 0.82, whereas the typical error was 17.2%. CONCLUSIONS: Gender, but not age, is an important factor when abdominal endurance is compared between adolescents. Finally, the BTC is a reliable test, supporting the findings of this study. However, an extensive familiarization period to reduce the learning effect is necessary.

Utility of high density multielectrode mapping during ablation of scar-related ventricular tachycardia.

INTRODUCTION: Multielectrode mapping catheters (MEMC) allow the performance of high resolution and density maps but the utility of these catheters in ventricular tachycardia (VT) ablation procedures has not been yet widely described. We sought to evaluate the utility of a MEMC during scar-related VT ablation procedures. METHODS: Eighty-five consecutive scar-related VT ablation procedures were performed in 81 patients. In the first 26 procedures, a standard 3.5-mm tip linear catheter was employed for endocardial/epicardial mapping (control group). In the following 59 procedures mapping was performed with a MEMC (study group). Procedural time, LV endocardial and epicardial mapping time, complications and ablation outcomes were compared. RESULTS: The use of the MEMC resulted in a significant shortening of the endocardial and epicardial mapping times (38 ± 15 minutes vs. 56 ± 24 minutes for endocardial LV mapping in the study and control group, respectively, P = 0.001; and 28 ± 9 minutes vs 41 ± 16 minutes, for epicardial mapping, P = 0.011) as well as the total procedural time (177 ± 53 minutes vs. 206 ± 50 minutes, respectively, P = 0.02). The mapping density was also significantly increased in the study group (mean endocardial LV points: 2,143 ± 1,419 vs. 485 ± 174, for the study and control group, respectively, P < 0.0001), specially within the scar area (49.6 ± 34 points/cm2 vs. 8.4 ± 4.6 points/cm2 , P < 0.001). No differences in acute and long-term follow-up outcomes were observed. CONCLUSIONS: High-density multielectrode mapping is associated with a significant reduction of procedural and mapping times and a significant increase of mapping density without affecting outcomes in patients with scar-related VT.

Genotype and phenotype spectrum of NRAS germline variants.

RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly conserved RAS-MAPK signalling pathway that lead to dysregulation of cell signal transmission. Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants) to Noonan and Cardiofaciocutaneous syndromes (KRAS variants). A small number of RASopathy cases with disease-causing germline NRAS alterations have been reported. Affected individuals exhibited features fitting Noonan syndrome, and the observed germline variants differed from the typical oncogenic NRAS changes occurring as somatic events in tumours. Here we describe 19 new cases with RASopathy due to disease-causing variants in NRAS. Importantly, four of them harbored missense changes affecting Gly12, which was previously described to occur exclusively in cancer. The phenotype in our cohort was variable but well within the RASopathy spectrum. Further, one of the patients (c.35G>A; p.(Gly12Asp)) had a myeloproliferative disorder, and one subject (c.34G>C; p.(Gly12Arg)) exhibited an uncharacterized brain tumour. With this report, we expand the genotype and phenotype spectrum of RASopathy-associated germline NRAS variants and provide evidence that NRAS variants do not spare the cancer-associated mutation hotspots.

Rapid detection and quantitation of ganciclovir resistance in cytomegalovirus quasispecies.

Human cytomegalovirus (HCMV) may cause severe or fatal disease among immunocompromised patients. The first line prophylaxis and systemic HCMV disease therapy is ganciclovir (GCV). The presence of GCV-resistant virus has been linked to fatal HCMV disease. The implementation of rapid and sensitive techniques for the early detection and monitoring of GCV-resistance may be helpful to support antiviral therapy management. A pyrosequencing assay for the detection and quantitation of the most frequent mutations conferring moderate- and high-grade GCV resistance was implemented. The pyrosequencing achieved an analytical sensitivity for adequate interpretation of ≥10(3) copies/ml. The assay was validated with 18 whole blood samples taken over a 6-month period from an umbilical cord blood recipient infected persistently with HCMV and allowed the detection and monitoring of the M460I and A594V GCV-resistant mutations. The percentage of resistant quasispecies ranged from 7.9% to 55.2% for the M460I mutation and from 19.8% to 43% for the A594V mutation. Clearance of the M460I mutation occurred in parallel with a decrease in the HCMV viremia, while the A594V mutation persisted. The pyrosequencing method for detection of GCV is sensitive enough to be used directly on clinical samples for the early identification of resistance mutations and allows the quantitation of resistant and wild type virus quasispecies within hours. The quantitation of minor resistant variants is an important issue to understand their relationship with viral load modification, and potentially anticipate treatment adjustment.