Individuals with high bone mass have increased progression of radiographic and clinical features of knee osteoarthritis.

OBJECTIVE: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. DESIGN: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score≥+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. RESULTS: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean (SD) age was 58 (12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR = 1.55 [0.56.4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45 [0.01.0.89] and 0.15 [0.01.0.29], respectively). HBM individuals had higher WOMAC knee pain scores (ß = 7.42 [1.17.13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. CONCLUSIONS: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Combining genomewide association study and lung eQTL analysis provides evidence for novel genes associated with asthma.

BACKGROUND: Genomewide association studies (GWASs) of asthma have identified single-nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor's diagnosed) asthma to our GWAS of asthma with BHR. METHODS: A GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts, and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. RESULTS: A total of 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genomewide significance after meta-analysis. Five of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma-associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. CONCLUSIONS: Combining GWAS with subsequent lung eQTL analysis revealed disease-associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor's diagnosed) asthma.

Pet ownership is associated with increased risk of non-atopic asthma and reduced risk of atopy in childhood: findings from a UK birth cohort.

BACKGROUND: Studies have shown an inverse association of pet ownership with allergy but inconclusive findings for asthma. OBJECTIVE: To investigate whether pet ownership during pregnancy and childhood was associated with asthma and atopy at the age of 7 in a UK population-based birth cohort. METHODS: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time points from pregnancy to the age of 7 with asthma, atopy (grass, house dust mite, and cat skin prick test) and atopic vs. non-atopic asthma at the age of 7 using logistic regression models adjusted for child's sex, maternal history of asthma/atopy, maternal smoking during pregnancy, and family adversity. RESULTS: A total of 3768 children had complete data on pet ownership, asthma, and atopy. Compared with non-ownership, continuous ownership of any pet (before and after the age of 3) was associated with 52% lower odds of atopic asthma [odds ratio (OR) 0.48, 95% CI 0.34-0.68]. Pet ownership tended to be associated with increased risk of non-atopic asthma, particularly rabbits (OR 1.61, 1.04-2.51) and rodents (OR 1.86, 1.15-3.01), comparing continuous vs. non-ownership. Pet ownership was consistently associated with lower odds of sensitization to grass, house dust mite, and cat allergens, but rodent ownership was associated with higher odds of sensitization to rodent allergen. Differential effects of pet ownership on atopic vs. non-atopic asthma were evident for all pet types. CONCLUSIONS AND CLINICAL RELEVANCE: Pet ownership during pregnancy and childhood in this birth cohort was consistently associated with a reduced risk of aeroallergen sensitization and atopic asthma at the age of 7, but tended to be associated (particularly for rabbits and rodents) with an increased risk of non-atopic asthma. The opposing effects on atopy vs. non-atopic asthma might be considered by parents when they are deciding whether to acquire a pet.

Maternal 25-hydroxyvitamin D and its association with childhood atopic outcomes and lung function.

BACKGROUND: It has been suggested that maternal vitamin D status in pregnancy influences the risk of asthma and atopy in the offspring. The epidemiological evidence to support these claims is conflicting and may reflect chance findings and differences in how vitamin D was assessed. OBJECTIVE: To examine the association between blood total maternal 25-hydroxy vitamin D (25(OH)D) concentrations in pregnancy and offspring asthma, atopy and lung function in the largest birth cohort study to date. METHODS: Participants were largely of white European origin and resident in the South West of England. We examined the associations of maternal 25(OH)D concentrations in pregnancy with the following outcomes in the offspring: wheeze, asthma, atopy, eczema, hayfever, at mean age 7.5 years (n = 3652-4696 depending on outcome), IgE at 7 years (n = 2915) and lung function and bronchial responsiveness at mean age 8.7 years (n = 3728-3784). RESULTS: Sixty-eight per cent of mothers had sufficient (> 50 nmol/L) concentrations of 25(OH)D, 27% were insufficient (27.5-49.99 nmol/L) and 5% were deficient (< 27.5 nmol/L). There was no evidence to suggest that maternal 25(OH)D concentration in pregnancy was associated with any respiratory or atopic outcome in the offspring. These findings remained after adjustment for season of measurement and for potential confounders. There was also no evidence that these relationships followed a non-linear form and no evidence that either deficient or high concentrations of maternal 25(OH)D were associated with atopic or respiratory outcomes. CONCLUSIONS: We found no evidence that maternal blood 25(OH)D concentration in pregnancy is associated with childhood atopic or respiratory outcomes.

Genome-wide association study of body mass index in 23 000 individuals with and without asthma.

BACKGROUND: Both asthma and obesity are complex disorders that are influenced by environmental and genetic factors. Shared genetic factors between asthma and obesity have been proposed to partly explain epidemiological findings of co-morbidity between these conditions. OBJECTIVE: To identify genetic variants that are associated with body mass index (BMI) in asthmatic children and adults, and to evaluate if there are differences between the genetics of BMI in asthmatics and healthy individuals. METHODS: In total, 19 studies contributed with genome-wide analysis study (GWAS) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. RESULTS: We report associations between several DENND1B variants (P = 2.2 × 10(-7) for rs4915551) on chromosome 1q31 and BMI from a meta-analysis of GWAS data using 2691 asthmatic children (screening data). The top DENND1B single nucleotide polymorphisms(SNPs) were next evaluated in seven independent replication data sets comprising 2014 asthmatics, and rs4915551 was nominally replicated (P < 0.05) in two of the seven studies and of borderline significance in one (P = 0.059). However, strong evidence of effect heterogeneity was observed and overall, the association between rs4915551 and BMI was not significant in the total replication data set, P = 0.71. Using a random effects model, BMI was overall estimated to increase by 0.30 kg/m(2) (P = 0.01 for combined screening and replication data sets, N = 4705) per additional G allele of this DENND1BSNP. FTO was confirmed as an important gene for adult and childhood BMI regardless of asthma status. CONCLUSIONS AND CLINICAL RELEVANCE: DENND1B was recently identified as an asthma susceptibility gene in a GWAS on children, and here, we find evidence that DENND1B variants may also be associated with BMI in asthmatic children. However, the association was overall not replicated in the independent data sets and the heterogeneous effect of DENND1B points to complex associations with the studied diseases that deserve further study.

Glutathione-S-transferase P1, early exposure to mould in relation to respiratory and allergic health outcomes in children from six birth cohorts. A meta-analysis.

BACKGROUND: There are conflicting study results regarding the association of exposure to visible mould and fungal components in house dust with respiratory and allergic diseases in children. It has been suggested that functional polymorphisms of the GSTP1 gene may influence the risk for allergic disorders through an impaired defence against oxidant injury. METHODS: We examined in six birth cohorts of over 14 000 children whether the association between early exposure to reported mould at home in relation to respiratory and allergic diseases is modified by a single nucleotide polymorphism of the GSTP1 gene. RESULTS: We observed a positive association of mould exposure with nasal symptoms (2-10 year) aOR: 1.19 (1.02-11.38). Further, there was a borderline significant increased risk of rhinoconjunctivitis (6-8 year) in children homozygous for the minor allele Val/Val, aOR: 1.25 (0.98-1.60). In stratified analyses, subjects homozygous for the minor allele and exposed to mould at home were at increased risk for early wheezing aOR: 1.34 (1.03-1.75), whereas the major allele may confer susceptibility for later nasal outcomes, (6-8 year) aOR: 1.20 (1.00-1.45) and (2-10 year) aOR: 1.30 (1.04-1.61), respectively. For none of the health outcomes studied, we found gene by environment interactions. CONCLUSION: A genetic influence of the GSTP1 gene cannot be ruled out, but the magnitude of the effect is a matter of further research. In conclusion, the interplay between gene and environments is complex and remains subject of further study.

Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative.

BACKGROUND: Several cross-sectional studies during the past 10 years have observed an increased risk of allergic outcomes for children living in damp or mouldy environments. OBJECTIVE: The objective of this study was to investigate whether reported mould or dampness exposure in early life is associated with the development of allergic disorders in children from eight European birth cohorts. METHODS: We analysed data from 31 742 children from eight ongoing European birth cohorts. Exposure to mould and allergic health outcomes were assessed by parental questionnaires at different time points. Meta-analyses with fixed- and random-effect models were applied. The number of the studies included in each analysis varied based on the outcome data available for each cohort. RESULTS: Exposure to visible mould and/or dampness during first 2 years of life was associated with an increased risk of developing asthma: there was a significant association with early asthma symptoms in meta-analyses of four cohorts [0-2 years: adjusted odds ratios (aOR), 1.39 (95% CI, 1.05-1.84)] and with asthma later in childhood in six cohorts [6-8 years: aOR, 1.09 (95% CI, 0.90-1.32) and 3-10 years: aOR, 1.10 (95% CI, 0.90-1.34)]. A statistically significant association was observed in six cohorts with symptoms of allergic rhinitis at school age [6-8 years: aOR, 1.12 (1.02-1.23)] and at any time point between 3 and 10 years [aOR, 1.18 (1.09-1.28)]. CONCLUSION: These findings suggest that a mouldy home environment in early life is associated with an increased risk of asthma particularly in young children and allergic rhinitis symptoms in school-age children.

Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood.

BACKGROUND: Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals. METHODS: Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV(1)), mid forced expiratory flow (FEF(25-75))) and bronchial responsiveness were made at 7-9 years of age. RESULTS: Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV(1) per mumol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV(1) per mumol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes. CONCLUSIONS: The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.

The association between mother and child MTHFR C677T polymorphisms, dietary folate intake and childhood atopy in a population-based, longitudinal birth cohort.

BACKGROUND: A recent study suggested a link between folate metabolism and atopy, based on a positive association between a common polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and allergic sensitization in Danish adults. OBJECTIVE: We investigated the associations between MTHFR C677T and allergy or atopy in a large, population-based birth cohort of children and their mothers, the Avon Longitudinal Study of Parents and Children (ALSPAC). We also looked for evidence of a pre-natal effect of maternal folate metabolism on subsequent atopic disease in the offspring. METHODS: Mothers were recruited in pregnancy and the children followed from birth. Atopy in the child was assessed at 7-8 years of age by skin prick tests to common allergens. Asthma was defined as a physician diagnosis and current symptoms at 71/2 years of age. Asthma and allergy status of the mothers were obtained from self-completion questionnaires. RESULTS: Data on MTHFR C677T genotype and allergy were available for 5364 children and on allergy and/or asthma for 7356 mothers. In children, the prevalence of atopy was 20.0% and asthma 10.0% whereas in mothers, the prevalence of self-reported allergy was 42.7% and asthma 11.5%. Atopy in the child was associated with male gender (P<0.001), less tobacco smoke exposure and higher maternal education. MTHFR C677T genotype was not associated with social factors or dietary folate intake. We found no evidence of associations between the MTHFR C677T variant allele and atopy, allergy or asthma in mothers or children. There was no evidence to support an effect of maternal MTHFR C677T genotype on atopy in the offspring. CONCLUSION: The results of this study do not support the hypothesis that impaired folate metabolism is associated with allergy in adults or children in this population.

Usefulness of cardiac resynchronisation therapy devices and implantable cardioverter defibrillators in the treatment of heart failure due to severe systolic dysfunction: systematic review of clinical trials and network meta-analysis.

AIM: To assess the effectiveness of cardiac resynchronisation therapy (CRT), implantable cardioverter defibrillator (ICD) therapy, and the combination of these devices (CRT+ICD) in adult patients with left ventricular dysfunction and symptomatic heart failure. METHODS: A comprehensive systematic review of randomised clinical trials was conducted. Several electronic databases (PubMed, Embase, Ovid, Cochrane, ClinicalTrials.gov) were reviewed. The mortality rates between treatments were compared. A network was established comparing the various options, and direct, indirect and mixed comparisons were made using multivariate meta-regression. The degree of clinical and statistical homogeneity was assessed. RESULTS: 43 trials involving 13 017 patients were reviewed. Resynchronisation therapy, defibrillators, and combined devices (CRT+ICD) are clearly beneficial compared to optimal medical treatment, showing clear benefit in all of these cases. In a theoretical order of efficiency, the first option is combined therapy (CRT+ICD), the second is CRT, and the third is defibrillator implantation (ICD). Given the observational nature of these comparisons, and the importance of the overlapping CIs, we cannot state that the combined option (CRT+ICD) offers superior survival benefit compared to the other two options. CONCLUSIONS: The combined option of CRT+ICD seems to be better than the option of CRT alone, although no clear improvement in survival was found for the combined option. It would be advisable to perform a direct comparative study of these two options.

[The tilt-table test: is it essential for adequate treatment of vasovagal syncope? Arguments against]. / Test de mesa basculante: es imprescindible para el tratamiento adecuado del síncope vasovagal? Argumentos en contra.

The knowledge about vasovagal syncope has hugely grown since its initial description by Lewis in 1932. Nevertheless some critical gaps remain, affecting specially to the patient management. There are not enough data about the natural history of the process and, because of that, no useful markers are known to identify patients who need or would benefit from a specific treatment. A diagnostic test with a sensibility/specificity relationship good enough to be a diagnostic gold standard is lacking. Although tilt-table test can be helpful in diagnosis, its sensitivity is, nowadays, unknown. Available data about reproducibility of tilt test are scarce and sometimes contradictory, specially with positive tilt test results. Should the lack of reproducibility of positive results found by some authors be confirmed, the usefulness of serial tilt tests in selecting treatment would be seriously affected. No evidence about the existence of an effective treatment for vasovagal syncope has been published yet, not either about the advantage of an specific strategy in selecting it. Therefore, tilt test has not been proved to be a more useful tool in selecting therapy for patients with vasovagal syncope.

[Diagnostic accuracy of a protocol in the evaluation of unexplained syncope]. / Rendimiento diagnóstico de un protocolo de estudio del síncope de causa no aparente.

INTRODUCTION AND OBJECTIVES: To assess the diagnostic capacity of a protocol to study syncope of unknown cause in which electrophysiological studies and tilting table tests are selectively used. PATIENTS AND METHODS: The study was performed in 137 consecutive patients (94 men and 43 women, with a mean age of 57.6+/-18.3 years) with syncope of unknown cause after the initial clinical evaluation, who were divided into two groups. Group A consisted of 77 patients meeting any of the following criteria: a) presence of structural heart disease; b) abnormal ECG; c) presence of significant non-symptomatic arrhythmia in the Holter recording, and d) presence of paroxysmal palpitations. These patients initially underwent an electrophysiological study. Group B consisted of 60 patients not meeting any of the above criteria, who were initially submitted to tilting table tests.Results. In group A, the electrophysiological study was positive in 43 patients (55%). In group B, the tilting test was positive in 41 patients (68%). Among patients in group A with a negative study, 20 (59%) were submitted to the tilting table test, with positive results in 7 cases (35%). Five patients from group B with a negative tilting test underwent the electrophysiological study, which was negative in all of them. Overall, a positive diagnosis was achieved in 91 of 137 patients (66%). CONCLUSIONS: In patients with syncope of a non-apparent cause in the initial assessment, selective use of electrophysiological studies or tilting table tests, guided by clinical criteria, allows for a positive diagnosis in over 60% of the cases. Our results suggest that the tilting table test should be performed in cases of group A with a negative electrophysiological study.

[Late potentials in patients during the hospitalization period following acute myocardial infarction]. / Potenciales tardíos en la fase hospitalaria del infarto agudo de miocardio.

Serial signal-averaged electrocardiograms were recorded every 72 hours in 60 patients admitted to the coronary care unit with acute myocardial infarction. The prevalence of late potentials was 61.6% (37 patients) during hospitalization. Of these 37 patients, late potentials appeared transiently in 20 (54%), while in 9 patients (24%), once late potentials had appeared, they tended to persist. No specific clinical characteristics were related to the development of late potentials (site of infarction, peak creatine kinasa activity, Killip class, thrombolytic therapy). The presence of late potentials did not identify patients who developed clinically significant ventricular tachyarrhythmias (primary ventricular fibrillation, ventricular tachycardia). The abnormal late potentials were modified by the administration of lidocaine. This lack of correlations suggests that the abnormal signal averaged electrocardiogram and complex ventricular arrhythmias during acute myocardial infarction have different electrophysiological bases. Late potentials could be only a bystander electrophysiological phenomenon without clinical correlation in this clinical phase.

[Atypical bidirectional tachycardias]. / Taquicardias bidireccionales atípicas.

Two cases of bidirectional tachycardia are presented. The ventricular origin of these arrhythmias was assessed by His bundle recordings. Because of the V1 morphology of the ventricular complexes during tachycardia in one case and the unknown etiology in the other, these arrhythmias were considered to be atypical. The involved mechanisms and the causes inducing these tachycardias are discussed. Whatever the involved mechanism, our cases reaffirm the opinion that the terminology bidirectional tachycardia should be used only to describe an electrocardiographic pattern that may be caused by different electrophysiological mechanisms.

[50 hz alternating current as a cause of inhibition of monopolar ventricular pacemakers]. / Corriente alterna de 50 Hz como causa de inhibición de marcapasos ventriculares monopolares.

It is not well established the importance of 50 Hz alternating current (AC) (that supplies most of house appliances) as a source of inappropriate inhibition of today cardiac pacemakers (PM). This problem has been studied in 58 consecutive patients permanently paced (VVI unipolar) for AV block with 27 different PM models from 11 manufacturers. Under ECG monitoring, 50 Hz AC was applied through a pair of electrodes set at both patient's wrists using a battery powered external source, with voltage ranging between 0 and 45 V. Inappropriate inhibition was considered if PM pauses longer than twice the programmed escape interval of the PM were observed during interference. This happened in 46 patients (79.3%), with PM from all 11 manufacturers, with voltages ranging from 3 to 28 V. In each case, inhibition was seen with a narrow voltage window between no interference detection and interference reversion of the PM. Only 3 patients (5.2%) referred perception of electrical current during the study. Three of the patients studied had complained, prior to the study, about dizziness or presyncope related to touching electrical devices and in all of them inappropriate inhibition was observed during interference. We conclude that: 1) it is possible to demonstrate inappropriate inhibition caused by 50 Hz AC galvanic interference in a high percentage of unipolar PM; 2) This inhibition occurs at current levels that in most cases are not sensed by the cutaneous nerves, and 3) although the problem seems to have little clinical significance it should be investigated in paced patients with symptoms attributable to inappropriate inhibition of their PM.

[An analysis of heart rate variability. Spectrum analysis methods and complex signal demodulation]. / Análisis de la variabilidad de la frecuencia cardíaca. Métodos espectrales y demodulación compleja de la señal.

The analysis of heart rate variability provides valuable information in the noninvasive study of neurovegetative activity and its modifications induced by drugs, physiological maneuvers or disease processes, and in the evaluation of prognosis and risk stratification in different cardiovascular diseases. A review is made of the different methods used to study heart rate variability, and an account is given of the information provided by spectral methods and the new procedures based on the complex demodulation of the time series composed of consecutive cardiac cycles. The limitations of the spectral methods are deal with, particularly in defining the time-dependent changes in variability and their relation to clinical events. Likewise, a description is given of the ability of complex demodulation to define the time course of the oscillations into which the analyzed time series is decomposed. Complex demodulation based on the fast Fourier transform and its inverse is able to establish the instantaneous amplitude and frequency of each of the oscillations contained in the time series, separated by specific filters in the previously selected frequency bands (high: 0.15-0.40 Hz, low: 0.04-0.15 Hz, or very low: < 0.04 Hz), and from which the original signal may be reconstructed. The evaluation of the different methodological approaches, and the analysis of the causal relations between the variability modifications and clinical events will further extend the clinical relevance of the study of heart rate variability.

[Heart rate-ventricular extrasystole relations and their dependence on circadian rhythms]. / Estudio de las relaciones frecuencia-extrasistolia ventricular y su dependencia de ritmos circadianos.

The linear correlation of the circadian rhythms (CR) of heart rate (HR) with those of ventricular extrasystole (VE) is analyzed by electrocardiographic ambulatory monitoring in 32 patients: 22 with ischemic post-infarction cardiopathy (group A) and ten free of structural cardiopathy (group B). Variability expressed as the coefficient of ventricular extrasystole variation (100 x standard deviation/mean) presented an inverse correlation with the number of recording extrasystoles. Linear correlation between HR and VE was statistically significant in 72% of recordings in group A, and in 60% in group B. The percentage of cases with significant linear correlation was greater on analyzing the three-minute periods than with the longer periods. When the cases analyzed presented over 200 extrasystoles, the percentage with significant linear correlation between HR and extrasystole was greater in group A than in group B. The circadian rhythm of the ventricular extrasystoles using interpolation of a cosinor function was significant in 50% of group A cases, and in 60% of group B. The achrophases were diurnal in group B, but only in 45% of cases in group A, two correspondence models being found between the CR achrophases and the inverse linear correlation between HR and VE.

[Recurrent syncope in patients with sick sinus syndrome carrying a permanent pacemaker]. / Síncopes recurrentes en pacientes con enfermedad del nodo sinusal portadores de marcapasos definitivo.

BACKGROUND: It is clear that permanent cardiac pacing in patients with sick sinus syndrome is effective. In spite of a normal pacemaker function, syncope may occur. Causes often remain unknown. The objective of this study was to review our current experience with these patients to identify predictors and etiologies of these symptoms. METHOD AND RESULTS: We studied 153 patients who received atrial, ventricular and dual-chamber pacemakers for sick sinus syndrome. During a median follow-up of 57.6 months (1-177 months), actuarial incidence of syncope or near syncope was 4.5% at 1 year, 9% at 5 years and 13% at 10 years. Causes were related with autonomic insufficiency (45%), pacemaker/lead malfunction (30%), pacemaker syndrome (10%) and conduction disturbances in patients with AAI pacemakers (10%). In only one patient (5%) syncope remained unexplained. Preimplant predictors for syncope were gender (male) and age (< 70 years old). CONCLUSIONS: 1) Syncopes in paced patients with sick sinus syndrome have multiple etiologies and may be multifactorial; 2) Autonomic dysfunction and "oversensing" in troubleshooting of implanted cardiac pacemakers could provide an explanation for recurrent syndrome in over 70% of these patients; 3) A better evaluation of neurogenic syncope may be necessary before pacemakers are implanted, to prevent recurrent syncope.

[Auricular fibrillation and stroke in patients with sick sinus syndromeusing permanent pacemakers]. / Fibrilación auricular y accidente vascular encefálico en pacientes con enfermedad del nodo sinusal portadores de marcapasos definitivos.

INTRODUCTION AND OBJECTIVES: Since physiological pacing systems have become available, a debate has raged about the merits of atrial versus ventricular pacing in the sick sinus syndrome. The goal of this retrospective report was to study the long term incidence and the independent predictors for atrial fibrillation and stroke in 153 paced patients with sick sinus syndrome, adjusting for differences in baseline clinical variables with multivariate analysis. METHOD AND RESULTS: From 1980 to 1994, we implanted 32 dualchamber, 33 atrial, and 88 ventricular pacemakers to treat patients with sick sinus syndrome. After a maximum follow-up of 177 months (median 30 months for paroxismal atrial fibrillation, 45 months for chronic atrial fibrillation and 43,5 months for stroke) the actuarial incidence of paroximal atrial fibrillation was 7.8% at 1 year, 29% at 5 years and 42% at 10 years. The actuarial incidence of chronic atrial fibrillation was 1.3% at 1 year, 9.8% at 5 years and 22% at 10 years. Independent predictors for paroxismal AF from Cox's model was history of atrial tachyarrhythmias (p < 0.0001), chronic obstructive pulmonary disease (p = 0,006) and age (> 70 years-old) (p = 0.035). Only a history of atrial tachyarrhythmias before pacemaker implant was an independent predictor for chronic atrial fibrillation (p < 0.0001). The odd ratio for paroxismal atrial fibrillation in patients with previous atrial tachyarrhythmias and chronic atrial fibrillation were 6 (2.8-12) and 4 (1.6-9.7) (95% confiance limits). Actuarial incidence of stroke was 3% at 1 year, 10% at 5 years and 14% at 10 years. Independent predictors for stroke were history of peripheral vascular disease (p = 0.033) and hypertensive cardiomyopathy (p = 0.015). Development of paroxysmal and chronic atrial fibrillation during the follow-up were higher in patients with stroke (p < 0.001 and p < 0.05). CONCLUSIONS: Development of atrial fibrillation and stroke in paced patients with sick sinus syndrome are strongly determined by clinical variables. Preimplant paroxysmal atrial tachyarrhythmias is the most important predictor for atrial fibrillation in the follow-up.