Modifications of long-term heart rate variability produced in an experimental model of diet-induced metabolic syndrome.

Metabolic syndrome (MetS) has been linked to a higher prevalence of cardiac arrhythmias, the most frequent being atrial fibrillation, but the mechanisms are not well understood. One possible underlying mechanism may be an abnormal modulation of autonomic nervous system activity, which can be quantified by analysing heart rate variability (HRV). Our aim was to investigate the modifications of long-term HRV in an experimental model of diet-induced MetS to identify the early changes in HRV and the link between autonomic dysregulation and MetS components. NZW rabbits were randomly assigned to control (n = 10) or MetS (n = 10) groups, fed 28 weeks with high-fat, high-sucrose diet. 24-hour recordings were used to analyse HRV at week 28 using time-domain, frequency-domain and nonlinear analyses. Time-domain analysis showed a decrease in RR interval and triangular index (Ti). In the frequency domain, we found a decrease in the low frequency band. Nonlinear analyses showed a decrease in DFA-α1 and DFA-α2 (detrended fluctuations analysis) and maximum multiscale entropy. The strongest association between HRV parameters and markers of MetS was found between Ti and mean arterial pressure, and Ti and left atrial diameter, which could point towards the initial changes induced by the autonomic imbalance in MetS.

Identification of a lipid transfer protein as a new allergen from morus alba pollen

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¿Qué aporta la denominada «medicina integrativa» a la asistencia clínica científica cotidiana? / What does «integrative medicine» provide to daily scientific clinical care?

La medicina integrativa es un intento ambicioso y, a la vez, generoso de suplir las deficiencias del sistema de salud operativo en nuestras sociedades occidentales, lastradas por la limitación de tiempo disponible, sobre todo en consultas externas. Por otro lado, supone no finiquitar las posibilidades de cierta utilidad terapéutica contrastada a través de los siglos (China, India, etc.), amén de algunos recursos que no alcanzan el nivel de fiabilidad científica deseable, pero que suponen un cierto apoyo terapéutico en determinados casos (homeopatía, acupuntura, etc.), y que siguen requiriendo un abordaje científico. Finalmente, el recurso de productos botánicos (fitoterapia) constituye un amplio mundo de posibilidades en el que se debe avanzar por parte de las universidades —y se está haciendo— al ir adquiriendo dichas sustancias un marchamo farmacológico asentado en el método científico y en los criterios de la medicina basada en la evidencia. Con ello se evitaría la sinrazón que supone el enfrentamiento cotidiano entre la medicina convencional científica, a la que nos sometemos la inmensa mayoría de los pacientes, y las otras «orientaciones» diagnóstico-terapéuticas (medicina naturista, medicina alternativa, medicina complementaria, medicina centrada en el paciente y otras) (AU)

Integrative medicine is an ambitious and noble-minded attempt to address the shortcomings of the current public health systems in our Western societies, which is restricted by the limited time available, especially in outpatient clinics. Integrative medicine also does not limit the possibilities of useful therapies that have been tested over the centuries (from China, India, etc.) or of certain resources that do not achieve the level of desired scientific credibility but that present certain therapeutic support in specific cases (homeopathy, acupuncture, etc.) but still require a scientific approach. Finally, the resource of botanical products (phytotherapy) constitutes a wide range of possibilities that universities can (and do) make progress on by providing drug brands for these products through the use of the scientific method and evidence-based medical criteria. This approach will help avoid the irrationality of the daily struggle between conventional scientific medicine (which we apply to the immense majority of patients) and the other diagnostic-therapeutic «guidelines» (natural medicine, alternative medicine, complementary medicine, patient-focused medicine and others) (AU)

What does «integrative medicine¼ provide to daily scientific clinical care? / ¿Qué aporta la denominada «medicina integrativa¼ a la asistencia clínica científica cotidiana?

Integrative medicine is an ambitious and noble-minded attempt to address the shortcomings of the current public health systems in our Western societies, which is restricted by the limited time available, especially in outpatient clinics. Integrative medicine also does not limit the possibilities of useful therapies that have been tested over the centuries (from China, India, etc.) or of certain resources that do not achieve the level of desired scientific credibility but that present certain therapeutic support in specific cases (homeopathy, acupuncture, etc.) but still require a scientific approach. Finally, the resource of botanical products (phytotherapy) constitutes a wide range of possibilities that universities can (and do) make progress on by providing drug brands for these products through the use of the scientific method and evidence-based medical criteria. This approach will help avoid the irrationality of the daily struggle between conventional scientific medicine (which we apply to the immense majority of patients) and the other diagnostic-therapeutic «guidelines¼ (natural medicine, alternative medicine, complementary medicine, patient-focused medicine and others).

Symmetrical compression distance for arrhythmia discrimination in cloud-based big-data services.

The current development of cloud computing is completely changing the paradigm of data knowledge extraction in huge databases. An example of this technology in the cardiac arrhythmia field is the SCOOP platform, a national-level scientific cloud-based big data service for implantable cardioverter defibrillators. In this scenario, we here propose a new methodology for automatic classification of intracardiac electrograms (EGMs) in a cloud computing system, designed for minimal signal preprocessing. A new compression-based similarity measure (CSM) is created for low computational burden, so-called weighted fast compression distance, which provides better performance when compared with other CSMs in the literature. Using simple machine learning techniques, a set of 6848 EGMs extracted from SCOOP platform were classified into seven cardiac arrhythmia classes and one noise class, reaching near to 90% accuracy when previous patient arrhythmia information was available and 63% otherwise, hence overcoming in all cases the classification provided by the majority class. Results show that this methodology can be used as a high-quality service of cloud computing, providing support to physicians for improving the knowledge on patient diagnosis.

Nonparametric signal processing validation in T-wave alternans detection and estimation.

Although a number of methods have been proposed for T-Wave Alternans (TWA) detection and estimation, their performance strongly depends on their signal processing stages and on their free parameters tuning. The dependence of the system quality with respect to the main signal processing stages in TWA algorithms has not yet been studied. This study seeks to optimize the final performance of the system by successive comparisons of pairs of TWA analysis systems, with one single processing difference between them. For this purpose, a set of decision statistics are proposed to evaluate the performance, and a nonparametric hypothesis test (from Bootstrap resampling) is used to make systematic decisions. Both the temporal method (TM) and the spectral method (SM) are analyzed in this study. The experiments were carried out in two datasets: first, in semisynthetic signals with artificial alternant waves and added noise; second, in two public Holter databases with different documented risk of sudden cardiac death. For semisynthetic signals (SNR = 15 dB), after the optimization procedure, a reduction of 34.0% (TM) and 5.2% (SM) of the power of TWA amplitude estimation errors was achieved, and the power of error probability was reduced by 74.7% (SM). For Holter databases, appropriate tuning of several processing blocks, led to a larger intergroup separation between the two populations for TWA amplitude estimation. Our proposal can be used as a systematic procedure for signal processing block optimization in TWA algorithmic implementations.

A study of the SCN5A gene in a cohort of 76 patients with Brugada syndrome.

We aim to study the SCN5A gene in a cohort of Brugada syndrome (BS) patients and evaluate the genotype-phenotype correlation. BS is caused by mutations in up to 10 different genes, SCN5A being the most frequently involved. Large genomic rearrangements in SCN5A have been associated with conduction disease, but its prevalence in BS is unknown. Seventy-six non-related patients with BS were studied. Clinical characteristics and family risk profile were recorded. Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) of the SCN5A gene for identification of mutations and larger rearrangements were performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K, G1743R (detected in three families), V728I, N1443S and E1152X). Patients with mutations had a trend toward a higher proportion of spontaneous type I Brugada electrocardiogram (ECG) (87.5% vs 52.9%, p = 0.06) and had evidence of familial disease (62.5%, vs 23.5%, p = 0.03). The symptoms and risk profile of the carriers were not different from wild-type probands. There were non-significant differences in the prevalence of type I ECG, syncope and history of arrhythmia in carriers of selected polymorphisms. None of the patients had any deletion/duplication in the SCN5A gene. In conclusion, 10.5% of our patients had mutations in the SCN5A gene. Patients with mutations seemed to have more spontaneous type I ECG, but no differences in syncope or arrhythmic events compared with patients without mutations. Larger studies are needed to evaluate the role of polymorphisms in the SCN5A in the expression of the phenotype and prognosis. Large rearrangements were not identified in the SCN5A gene using the MLPA technique.

Modifications of mechanoelectric feedback induced by 2,3-butanedione monoxime and Blebbistatin in Langendorff-perfused rabbit hearts.

AIM: Myocardial stretching is an arrhythmogenic factor. Optical techniques and mechanical uncouplers are used to study the mechanoelectric feedback. The aim of this study is to determine whether the mechanical uncouplers 2,3-butanedione monoxime and Blebbistatin hinder or modify the electrophysiological effects of acute mechanical stretch. METHODS: The ventricular fibrillation (VF) modifications induced by acute mechanical stretch were studied in 27 Langendorff-perfused rabbit hearts using epicardial multiple electrodes and mapping techniques under control conditions (n = 9) and during the perfusion of 2,3-butanedione monoxime (15 mM) (n = 9) or Blebbistatin (10 µm) (n = 9). RESULTS: In the control series, myocardial stretch increased the complexity of the activation maps and the dominant frequency (DF) of VF from 13.1 ± 2.0 Hz to 19.1 ± 3.1 Hz (P < 0.001, 46% increment). At baseline, the activation maps showed less complexity in both the 2,3-butanedione monoxime and Blebbistatin series, and the DF was lower in the 2,3-butanedione monoxime series (11.4 ± 1.2 Hz; P < 0.05). The accelerating effect of mechanical stretch was abolished under 2,3-butanedione monoxime (maximum DF = 11.7 ± 2.4 Hz, 5% increment, ns vs baseline, P < 0.0001 vs. control series) and reduced under Blebbistatin (maximum DF = 12.9 ± 0.7 Hz, 8% increment, P < 0.01 vs. baseline, P < 0.0001 vs. control series). The variations in complexity of the activation maps under stretch were not significant in the 2,3-butanedione monoxime series and were significantly attenuated under Blebbistatin. CONCLUSION: The accelerating effect and increased complexity of myocardial activation during VF induced by acute mechanical stretch are abolished under the action of 2,3-butanedione monoxime and reduced under the action of Blebbistatin.

The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity.

The purpose of this study is to test the role that parasympathetic postganglionic neurons could play on the adaptive electrophysiological changes produced by physical training on intrinsic myocardial automatism, conduction and refractoriness. Trained rabbits were submitted to a physical training protocol on treadmill during 6 weeks. The electrophysiological study was performed in an isolated heart preparation. The investigated myocardial properties were: (a) sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c) atrial, conduction system and ventricular refractoriness. The parameters to study the refractoriness were obtained by means of extrastimulus test at four different pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200 and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular fibrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 µM), in order to block cholinergic receptors. Cholinergic receptor blockade did not modify either the increase in sinus cycle length, atrioventricular conduction and refractoriness (left ventricular and atrioventricular conduction system functional refractory periods) or the decrease of DF of VF. These findings reveal that the myocardial electrophysiological modifications produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.

Approach to seizures in the neonatal period: a European perspective.

UNLABELLED: In the neonatal period, seizures rank among the most common neurological symptoms, often indicating an underlying serious neurological condition. It is remarkable that although new tools have been incorporated into the diagnosis of neonatal seizures, there is no consensus about the therapeutic approach among different doctors and institutions. Hence, although phenobarbital is still considered the initial drug of choice, the protocols reported in the literature show a great variability in the approach to treatment of refractory seizures. We used a questionnaire to gain information regarding the treatment of seizures in the neonatal period in different European institutions. CONCLUSION: We conclude that phenobarbital is still the initial drug of choice followed by benzodiazepines, except in preterm infants with a birth weight below 1800 g. In refractory seizures, the use of continuous lidocaine infusion is most common. Of note, clinical studies with newer drugs have been mostly performed in the United States but not in Europe.

Acute disabling low-back pain during intravenous administration of amiodarone: could intravenous to oral switch therapy be a safe strategy?

We report for the first time a case of an acute disabling low-back pain episode during intravenous administration of amiodarone in a patient with atrial fibrillation. The symptoms completely resolved after terminating the infusion, and switching amiodarone from intravenous to oral administration was well tolerated.

[Clinical assessment of peritoneal drainages for necrotizing enterocolitis. A Bayesian approach]. / Evaluación del drenaje peritoneal en la enterocolitis necrosante mediante metodología bayesiana.

AIM: To assess effectiveness of peritoneal drainages for necrotizing enterocolitis. MATERIAL AND METHODS: Retrospective cohort study (years 2000 to 2006). Laparotomy or patient's death were considered as failure. STUDY VARIABLES: sex, gestational age, weight at delivery, Apgar score at minutes 1 and 5, modified Bell score, radiology and ventilatory status. RESULTS: 25 patients were diagnosed with necrotizing enterocolitis and treated with peritoneal drainages. Sample's Bell score was: 13(52%) Ia, 6 (24%) IIa, 5 (20%) IIb, and 1 (4%) IIIa. Mean gestational age was 31.8 (+/- 4.2) weeks, and mean weight 1,564 (+/- 810) g. Patients classified as Bell I presented statistically significat differences compared with Bell II-III as for radiology (unspecific), delivery weight (lower) and ventilatory status (higher mechanical ventilation rates). For the 12 patients with Bell scores II-III, peritoneal drains were enough for 5 cases (41.7%) and failed in 7 (58.3%), who were operated on. Multivariate analysis (logistic regression) was not able to show any conection with collected variables. However, a bayesian analysis using data from similar studies showed that the probability for drainage success rate to be higher than 50% is 99%. CONCLUSIONS: In our centre, 52% of peritoneal drainages were used in patinets with low clinical suspect for necrotizing enetrocolitis, maybe in relation with their lower body weight and need for ventilatory support. In patients affected with necrotizing enterocolitis, drainages were effective in 41.7%. Although limited for its retrospective nature, our study suggests that peritoneal drainages can be curative in, at least, 50% of patients with necrotizing enterocolitis without pneumoperitoneum and clinical signs of peritonitis.

Evaluación del drenaje peritoneal en la enterocolitisnecrosante mediante metodología bayesiana / Clinical assessment of peritoneal drainages for necrotizing enterocolitis. A bayesian approach

Introducción: El objetivo del presente estudio es evaluar la eficacia del drenaje peritoneal para la enterocolitis necrosante en la prácticaclínica. Material y métodos: Estudio de cohorte retrospectiva (periodo2000-2006). Se consideró como fracaso del tratamiento la indicación de laparotomía o el exitus del paciente. Variables del estudio: sexo, edad gestacional, peso al nacimiento, Apgar 1 y 5, estadio de Bell modificado, patrón radiológico y tipo de ventilación. Resultados: 25 pacientes fueron diagnosticados de enterocolitisy tratados inicialmente mediante drenaje peritoneal. La distribución según estadios de Bell fue: 13 (52%) Ia, 6 (24%) IIa, 5 (20%) IIb, y 1(4%) IIIa. La media de la edad gestacional fue de 31,8 (±4,2) semanas, y la del peso 1.564 (±810) g. Los pacientes con estadio I presentaron diferencias estadísticamente significativas en cuanto al patrón radiológico (más inespecífico), peso al nacimiento (menor peso) y tipo de ventilación (mayor necesidad de soporte ventilatorio), que los pacientes con estadios II-III. En los 12 casos restantes el drenaje fue efectivo (..) (AU)

Aim: To assess effectiveness of peritoneal drainages for necrotizing enterocolitis. Material and methods: Retrospective cohort study (years 2000 to2006). Laparotomy or patient’s death were considered as failure. Study variables: sex, gestational age, weight at delivery, Apgar score at minutes 1 and 5, modified Bell score, radiology and ventilatory status. Results: 25 patients were diagnosed with necrotizing enterocolitis and treated with peritoneal drainages. Sample’s Bell score was: 13(52%)Ia, 6 (24%) IIa, 5 (20%) IIb, y 1 (4%) IIIa. Mean gestational age was31,8 (±4,2) weeks, and mean weight 1,564 (±810) g. Patients classified as Bell I presented statistically significat differences compared with BellII-III as for radiology (unspecific), delivery weight (lower) and ventilatory status (higher mechanical ventilation rates). For the 12 patients with Bell scores II-III, peritoneal drains were enough for 5 cases (41,7%)and failed in 7 (58,3%), who were operated on. Multivariate analysis(logistic regression) was not able to show any conection with collected variables. However, a bayesian analysis using data from similar studies showed that the probability for drainage success rate to be higher than 50% is 99%. Conclusions: In our centre, 52% of peritoneal drainages were used in patinets with low clinical suspect for necrotizing enetrocolitis, maybe (..) (AU)

Effects of chronic exercise on myocardial refractoriness: a study on isolated rabbit heart.

AIM: To determine whether chronic physical training increases atrial and ventricular refractoriness in isolated rabbit heart. METHODS: Trained rabbits were submitted to a protocol of treadmill running. The electrophysiological parameters of refractoriness investigated in an isolated heart preparation were: (1) atrial effective refractory period (AERP) and atrial functional refractory period and ventricular effective and functional refractory periods (VERP and VFRP) using the extrastimulus technique at four different pacing cycle lengths; (2) the dominant frequency (DF) of ventricular fibrillation (VF). A multi-electrode plaque containing 256 electrodes and a spectral method were used to obtain the mean, maximum and minimum DF of VF. Sinus cycle length of the isolated hearts was determined as an electrophysiological parameter of training. In vivo heart rate, myocardial heat shock proteins (HSP60) and inducible nitric oxide synthase were also determined in some animals as electrophysiological and biochemical markers of training respectively. RESULTS: VERP and VFRP were longer in the trained group than in the control group. The mean DF of VF was lower in the trained group than in the control group. Despite the fact that training did not significantly modify the AERP, it tended to be longer in the trained group (P = 0.09). CONCLUSION: Training seems to increase the electrical stability of ventricular myocardium. As the electrophysiological modifications were exhibited in hearts not submitted to extrinsic nervous system or humoral influences, they are, at least in part, intrinsic modifications. These electrophysiological data also suggest that training could protect against reentrant ventricular arrhythmias.

A halocin acting on Na+/H+ exchanger of Haloarchaea as a new type of inhibitor in NHE of mammals

The capability of halocin H6 (a bacteriocin-like protein produced by haloarchaeaHaloferax gibbonsii) to inhibit Na+/H+ exchange (NHE) in mammalian cells and its cardio-protective efficacy on the ischemic and reperfused myocardium were evaluated in the present study. H6 inhibits NHE activity (measured by a flow cytometry method) in a dose-dependent form of cell lines of mammalian origin (HEK293, NIH3T3, Jurkat and HL-1) as well as in primary cell culture from human skeletal muscle (myocytes and fibroblasts).In vivo, an ischemia-reperfusion model in dogs by coronary arterial occlusion was used (two hours of regional ischemia and three hours of reperfusion). In animals treated with halocin H6 there was a significant reduction of premature ventricular ectopic beats and infarct size, whereas blood pressure and heart rate remained unchanged. Up to date, halocin H6 is the only described biological molecule that exerts a, specific inhibitory activity in NHE of eukaryotic cells (AU)

En el presente trabajo se evalúa la capacidad de la halocina H6 (una proteína tipo bacteriocina producida por la haloarchaeaHaloferax gibbonsii) para inhibir el intercambiador Na+/H+ (NHE) de céludas de mamífero y su posible eficacia cardioprotectora frente a los daños causados por isquemia-reperfusión del miocardio. En experimentosin vitro H6 inhibe la actividad de NHE (determinada por citometría de flujo) de forma dosis-dependiente tanto en líneas celulares de mamíferos (HEK293, NIH3T3, Jurkat y HL-1) como en cultivos primarios de miocitos y fibroblastos aislados de músculo esquelético humano. En experimentosin vivo se utilizó un modelo de isquemia-reperfusión en perros por oclusión de la arteria coronaria (dos horas de isquemia y tres de reperfusión). En animales tratados con halocina H6 se produjo una disminución significativa a nivel estadístico, tanto del número de latidos ectópicos ventriculares como del tamaño del infarto, mientras que no se produjeron cambios tanto en la presión sanguínea como en el ritmo cardíaco. Hasta la fecha la halocina H6 es la única molécula biológica descrita que ejerce una actividad inhibidora específica sobre el NHE de células eucariotas (AU)

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats.

BACKGROUND AND PURPOSE: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor alpha production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment with thiopental and pentoxifylline. EXPERIMENTAL APPROACH: Pulmonary vascular permeability and arterial blood gases were measured, and a histological analysis was performed. The possible role of haemodynamic changes in the formation of pulmonary oedema was also assessed. KEY RESULTS: Co-administration of pentoxifylline and thiopental increased pulmonary vascular permeability and markedly decreased arterial pO2, with one third of rats suffering from hypoxemia. This combined treatment caused death by acute pulmonary oedema in 27% of normal rats and aggravated the respiratory insufficiency associated with acute pancreatitis in which the mortality rate increased to 60%. This pulmonary oedema was not mediated by cardiac failure or by pulmonary hypertension. CONCLUSIONS AND IMPLICATIONS: Co-administration of pharmacological doses of pentoxifylline and thiopental caused pulmonary oedema and death in rats. Consequently, pentoxifylline should not be administered when anaesthesia is induced with thiopental to avoid any possible risk of acute pulmonary oedema and death in humans.

A halocin acting on Na+/H+ exchanger of haloarchaea as a new type of inhibitor in NHE of mammals.

The capability of halocin H6 (a bacteriocin-like protein produced by haloarchaea Haloferax gibbonsii) to inhibit Na+/H+ exchanger (NHE) in mammalian cells and its cardio-protective efficacy on the ischemic and reperfused myocardium were evaluated in the present study. H6 inhibits NHE activity (measured by a flow cytometry method) in a dose-dependent form of cell lines of mammalian origin (HEK293, NIH3T3, Jurkat and HL-1) as well as in primary cell culture from human skeletal muscle (myocytes and fibroblasts). In vivo, an ischemia-reperfusion model in dogs by coronary arterial occlusion was used (two hours of regional ischemia and three hours of reperfusion). In animals treated with halocin H6 there was a significant reduction of premature ventricular ectopic beats and infarct size, whereas blood pressure and heart rate remained unchanged. Up to date, halocin H6 is the only described biological molecule that exerts a specific inhibitory activity in NHE of eukaryotic cells.

A new algorithm for rhythm discrimination in cardioverter defibrillators based on the initial voltage changes of the ventricular electrogram.

AIMS: Ventricular activation onset is faster in supraventricular beats than in ventricular rhythms. The aim of this study was to evaluate a criterion to differentiate supraventricular (SVT) from ventricular tachycardia (VT) based on the analysis of the initial voltage changes in ICD-stored morphology electrograms. METHODS: Far field ICD-stored EGMs were obtained from 68 VT and 38 SVT episodes in 16 patients. The first EGM peak was detected, three consecutive time epochs were defined within the preceding 80 ms window and the voltage changes with respect to a sinus template were analysed during each time period and combined into a single parameter for rhythm discrimination. RESULTS: The algorithm was tested in an independent validation group of 442 VT and 97 SVT spontaneous episodes obtained from 22 patients with a dual chamber ICD. The area under the receiver-operator characteristics (ROC) curve indicated that the arrhythmia separability with this method was 0.95 (tolerance interval: 0.85-0.99) and 0.98 (0.87-0.99) for the control and validation groups respectively. A specificity of 0.91 was obtained at 95% sensitivity in the validation group. CONCLUSION: The analysis of voltage changes during the initial ventricular activation process is feasible using the far field stored electrograms of an ICD system and yields a high sensitivity and specificity for arrhythmia discrimination.