Criteria to predict carriers of a novel SCN5A mutation in a large Portuguese family affected by the Brugada syndrome

Santos, Luís; Rodrigues, Bruno; Moreira, Davide; Correia, Emanuel; Currais, Luis; Costa, Ana Luísa; Elvas, Luís; Pereira, Telmo; Machado, José Carlos; Castedo, Sérgio; Henriques, Carla; Matos, Ana; Santos, Jerffson Lucas

doi:10.1093/europace/eur421

Cited by 14 publications

(16 citation statements)

References 15 publications

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“…Having as a starting point a BS diagnosis in a Portuguese Hospital Center (Tondela Viseu Hospital Center), records from family members were collected [18], [20] and a database began to be built. For this study, we considered the records of 64 members of two Portuguese families, from which we had information related to the five ECG markers being studied.…”

Section: Methodsmentioning

confidence: 99%

“…These markers are: P-wave duration (PR), transmural dispersion of repolarization (dQT) between V1 and V3, filtered QRS duration (QRSf), where QRS stands for the combination of three of the graphical deflections seen on a typical electrocardiogram (typically an ECG has five deflections, arbitrarily named P, Q, R, S and T waves), low-amplitude signal duration (LAS) and root-mean-square of the voltage in the last 40 ms of the fQRS (RMS40), the last three taken in a signal average ECG (see e.g. [18]). It was possible to offer genetic counseling to patients, by which 37 mutation carriers were identified within the 64 individuals.…”

Section: Methodsmentioning

confidence: 99%

“…As mentioned before, the diagnosis of BS is definitive only when the Brugada pattern is identified in an ECG, but this entails the problem of the constant fluctuations of the Brugada pattern [10], [19]. Earlier studies [11], [18], [20] have opened up new options in the diagnosis of BS, identifying five ECG markers with good potential to distinguish mutation from non-mutation carriers [18], and exploring ways of linearly combining these markers in order to enhance the ability of each one to discriminate between the two groups [11]. Exploring the logistic regression models of Henriques et al [11] further, in this study we assess the predictive ability of those models and also we apply shrinkage techniques to improve calibration and future predictions.…”

Section: Methodsmentioning

confidence: 99%

“…For a definitive diagnosis of BS, a specific pattern in an electrocardiogram (ECG), called Type 1 pattern or Brugada pattern, must be identified [18], [20]. However, it is well known that Brugada patients' ECGs often fluctuate between normal and non-normal patterns, which makes diagnosis challenging [10], [19].…”

Section: Introductionmentioning

confidence: 99%

“…In earlier studies, [11], [18], [20], five ECG markers were identified to have good ability to discriminate between carriers and non-carriers of the genetic mutation. Henriques et al [11] explored different ways of combining these five markers in order to enhance the ability of each one to discriminate between the two groups.…”

Section: Introductionmentioning

confidence: 99%

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Predictive Models for Mutation Carriers in Brugada Syndrome Screening

Henriques

Matos

Santos

2014

Computational Science and Its Applications – ICCSA 2014

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Abstract. In this study we consider logistic regression models to predict mutation carriers in family members affected by Brugada Syndrome. This Syndrome is an inherited cardiopathy that predisposes individuals without structural heart disease to sudden cardiac death. We focused on five electrocardiographic markers, which have been explored as good discriminators between carriers and non-carriers of the genetic mutation responsible for this disease. Logistic regression models which combine some of the five markers were investigated. Our objective was to assess the predictive ability of these models through internal validation procedures. We also applied shrinkage methods to improve calibration of the models and future predictive accuracy. Validation of these models, using bootstrapping, point to some superiority of two models, for which fairly good measures of predictive accuracy were obtained. This study provides confidence in these models, which offer greater sensitivity than the usual screening by detecting a characteristic pattern in an electrocardiogram.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Predictive Models for Mutation Carriers in Brugada Syndrome Screening

Henriques

Matos

Santos

2014

Computational Science and Its Applications – ICCSA 2014

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Brugada Syndrome Diagnosis: Three Approaches to Combining Diagnostic Markers

Henriques

Matos

Santos

2014

New Advances in Statistical Modeling and Applications

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Enhanced Risk Profiling of Implanted Defibrillator Shocks With Circulating SCN5A mRNA Splicing Variants

Gao

Brahmanandam

Raicu

et al. 2014

Journal of the American College of Cardiology

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Objectives The aim of this study was to determine the association of SCN5A cardiac sodium (Na+) channel mRNA splice variants in white blood cells (WBCs) with risk of arrhythmias in heart failure (HF). Background HF is associated with upregulation of two cardiac SCN5A mRNA splice variants. that encode prematurely truncated, nonfunctional Na+ channels. Since circulating WBCs demonstrate similar SCN5A splicing patterns, we hypothesized that these WBC-derived splice variants might further stratify HF patients at risk for arrhythmias. Methods Simultaneously obtained myocardial core samples and WBCs were compared for SCN5A variants C (VC) and D (VD). Circulating variant levels were compared between HF patients divided into three groups: HF without an implantable cardioverter-defibrillator (ICD), HF with an ICD without appropriate intervention, and HF with an ICD with appropriate intervention. Results Myocardial tissue-derived SCN5A variant expression levels strongly correlated with circulating WBC samples for both VC and VD variants (r = 0.78 and 0.75, respectively). After controlling for covariates, HF patients who had received an appropriate ICD intervention had higher expression levels of both WBC-derived SCN5A variants compared to HF patients with ICDs who had not (OR= 3.25 (95% CI 1.64–6.45; p=0.001)). Receiver operating characteristics analysis revealed that circulating SCN5A variants levels were highly associated with the risk for appropriate ICD intervention (area under the curve ≥ 0.97). Conclusions Circulating expression levels of SCN5A variants were strongly associated with myocardial tissue levels. Furthermore, circulating variant levels were correlative with arrhythmic risk as measured by ICD events in a HF population within one year.

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Criteria to predict carriers of a novel SCN5A mutation in a large Portuguese family affected by the Brugada syndrome

Abstract: The PC for BrS diagnosis should be implemented. Some parameters from the spontaneous ECG and the SAECG are more effective tools than the characteristic repolarization pattern to discriminate between carriers of SCN5A mutations.

Cited by 14 publications

References 15 publications

Predictive Models for Mutation Carriers in Brugada Syndrome Screening

Predictive Models for Mutation Carriers in Brugada Syndrome Screening

Brugada Syndrome Diagnosis: Three Approaches to Combining Diagnostic Markers

Enhanced Risk Profiling of Implanted Defibrillator Shocks With Circulating SCN5A mRNA Splicing Variants

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