FAMILY HISTORY OF SUDDEN CARDIAC DEATH IN BRUGADA SYNDROME: A SYSTEMIC REVIEW AND META-ANALYSIS

Background Brugada syndrome is an inherited cardiac channelopathy associated with major arrhythmic events (MAEs). The presence of a positive family history of sudden cardiac death (SCD) as a risk predictor of MAE remains controversial. We aimed to examine the association between family history of SCD and MAEs stratified by age of SCD with a systematic review and meta‐analysis. Methods and Results We searched the databases of MEDLINE and EMBASE from January 1992 to January 2020. Data from each study were combined using the random‐effects model. Fitted metaregression was performed to evaluate the association between the age of SCD in families and the risk of MAE. Twenty‐two studies from 2004 to 2019 were included in this meta‐analysis involving 3386 patients with Brugada syndrome. The overall family history of SCD was not associated with increased risk of MAE in Brugada syndrome (pooled odds ratio [OR], 1.11; 95% CI, 0.82–1.51; P =0.489, I 2 =45.0%). However, a history of SCD in family members of age younger than 40 years of age did increase the risk of MAE by ≈2‐fold (pooled OR, 2.03; 95% CI, 1.11–3.73; P =0.022, I 2 =0.0%). When stratified by the age of cut point at 50, 45, 40, and 35 years old, a history of SCD in younger family member was significantly associated with a higher risk of MAE (pooled OR, 0.49, 1.30, 1.51, and 2.97, respectively; P =0.046). Conclusions A history of SCD among family members of age younger than 40 years was associated with a higher risk of MAE.

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Diagnosis of Brugada Syndrome, a Rare Inherited Arrhythmogenic Disorder

Dubai Medical Journal ◽

10.1159/000507572 ◽

2020 ◽

Vol 3 (2) ◽

pp. 70-73

Author(s):

Juwairiya Syed Iqbaluddin ◽

Fathima Murthuza ◽

Sumaiya Iqbal

Keyword(s):

Family History ◽

Sudden Cardiac Death ◽

Brugada Syndrome ◽

Cardiac Death ◽

Genetic Disorder ◽

Positive Family History ◽

Provocation Test ◽

Increased Risk ◽

History Of ◽

Electrocardiogram Ecg

Brugada syndrome (BrS) is a rare, autosomal dominant genetic disorder with mutation in the SCN5A gene. It is associated with an increased risk of arrhythmias and sudden cardiac death. BrS can be diagnosed by characteristic electrocardiogram (ECG) findings and significant events, such as syncope, palpitations, nocturnal respiratory agonia, and family history of sudden cardiac death below the age of 45 years. Special investigations, such as electrophysiology study, ajmaline provocation test, and genetic testing, play an important role in its diagnosis. This case report describes a patient who presented with chest pain and dizziness along with a positive family history of sudden cardiac deaths below the age of 45 years. He was discovered to have type 2 Brugada pattern on ECG, and by ajmaline provocation test, the type 1 pattern was unmasked, which established a definitive diagnosis of BrS. The patient was then advised for an implantable cardioverter-defibrillator. This case highlights the need for physicians to be competent in identifying patients with BrS in order to provide the necessary management and prevent fatal outcomes.

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Genotype-Phenotype Correlation of SCN5A Genotype in Patients With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.120.003222 ◽

2021 ◽

Author(s):

Anat Milman ◽

Elijah R. Behr ◽

Belinda Gray ◽

David C. Johnson ◽

Antoine Andorin ◽

...

Keyword(s):

Family History ◽

Sudden Cardiac Death ◽

Brugada Syndrome ◽

Odds Ratio ◽

Cardiac Death ◽

Variants Of Unknown Significance ◽

Increased Risk ◽

Cardiac Sodium Channel ◽

Arrhythmic Event ◽

History Of

Background: Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event. Methods: Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and SCN5A genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed. Results: The study group comprised 392 probands: 92 (23.5%) SCN5A+ (44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A−. SCN5A missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with SCN5A− (11.4% versus 3%, P =0.023). The proportion of females was higher among patients with P/LP compared with SCN5A − (18.2% versus 6.3%, P =0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A − (41.9% versus 16.8%, P <0.001). A higher proportion of patients with P/LP were White compared with SCN5A− (87.5% versus 47%, P <0.001). Ethnicity (odds ratio, 5.41 [2.8–11.19], P <0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28–5.82], P =0.009) were independent variables associated with P/LP genotype following logistic regression. Conclusions: The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with SCN5A− . In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.

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Functional Characterization of Two Novel Mutations in SCN5A Associated with Brugada Syndrome Identified in Italian Patients

International Journal of Molecular Sciences ◽

10.3390/ijms22126513 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6513

Author(s):

Cristina Balla ◽

Elena Conte ◽

Rita Selvatici ◽

Renè Massimiliano Marsano ◽

Andrea Gerbino ◽

...

Keyword(s):

Family History ◽

Sudden Cardiac Death ◽

Brugada Syndrome ◽

Cardiac Death ◽

Sodium Current ◽

Functional Characterization ◽

Loss Of Function ◽

St Segment Elevation ◽

History Of

Background. Brugada syndrome (BrS) is an autosomal dominantly inherited cardiac disease characterized by “coved type” ST-segment elevation in the right precordial leads, high susceptibility to ventricular arrhythmia and a family history of sudden cardiac death. The SCN5A gene, encoding for the cardiac voltage-gated sodium channel Nav1.5, accounts for ~20–30% of BrS cases and is considered clinically relevant. Methods. Here, we describe the clinical findings of two Italian families affected by BrS and provide the functional characterization of two novel SCN5A mutations, the missense variant Pro1310Leu and the in-frame insertion Gly1687_Ile1688insGlyArg. Results. Despite being clinically different, both patients have a family history of sudden cardiac death and had history of arrhythmic events. The Pro1310Leu mutation significantly reduced peak sodium current density without affecting channel membrane localization. Changes in the gating properties of expressed Pro1310Leu channel likely account for the loss-of-function phenotype. On the other hand, Gly1687_Ile1688insGlyArg channel, identified in a female patient, yielded a nearly undetectable sodium current. Following mexiletine incubation, the Gly1687_Ile1688insGlyArg channel showed detectable, albeit very small, currents and biophysical properties similar to those of the Nav1.5 wild-type channel. Conclusions. Overall, our results suggest that the degree of loss-of-function shown by the two Nav1.5 mutant channels correlates with the aggressive clinical phenotype of the two probands. This genotype-phenotype correlation is fundamental to set out appropriate therapeutical intervention.

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Antidepressants and Risk of Sudden Cardiac Death: A Network Meta-Analysis and Systematic Review

Medical Sciences ◽

10.3390/medsci9020026 ◽

2021 ◽

Vol 9 (2) ◽

pp. 26

Author(s):

Narut Prasitlumkum ◽

Wisit Cheungpasitporn ◽

Nithi Tokavanich ◽

Kimberly R. Ding ◽

Jakrin Kewcharoen ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Mental Disorders ◽

Ventricular Arrhythmia ◽

Cardiac Death ◽

Selective Serotonin Reuptake Inhibitors ◽

Meta Analysis ◽

Tricyclic Antidepressant ◽

Systemic Review ◽

Analysis Model ◽

Antidepressant Use

Background: Antidepressants are one of the most prescribed medications, particularly for patients with mental disorders. Nevertheless, there are still limited data regarding the risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) associated with these medications. Thus, we performed systemic review and meta-analysis to characterize the risks of VA and SCD among patients who used common antidepressants. Methods: A literature search for studies that reported risk of ventricular arrhythmias and sudden cardiac death in antidepressant use from MEDLINE, EMBASE, and Cochrane Database from inception through September 2020. A random-effects model network meta-analysis model was used to analyze the relation between antidepressants and VA/SCD. Surface Under Cumulative Ranking Curve (SUCRA) was used to rank the treatment for each outcome. Results: The mean study sample size was 355,158 subjects. Tricyclic antidepressant (TCA) patients were the least likely to develop ventricular arrhythmia events/sudden cardiac deaths at OR 0.24, 0.028–1.2, OR 0.32 (95% CI 0.038–1.6) for serotonin and norepinephrine reuptake inhibitors (SNRI), and OR 0.36 (95% CI 0.043, 1.8) for selective serotonin reuptake inhibitors (SSRI), respectively. According to SUCRA analysis, TCA was on a higher rank compared to SNRI and SSRI considering the risk of VA/SCD. Conclusion: Our network meta-analysis demonstrated the low risk of VA/SCD among patients using antidepressants for SNRI, SSRI and especially, TCA. Despite the relatively lowest VA/SCD in TCA, drug efficacy and other adverse effects should be taken into account in patients with mental disorders.

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Abstract 3667: Comparison of Risk Profiles between Survivors and Victims of Sudden Cardiac Death of an Acute Coronary Event

Circulation ◽

10.1161/circ.116.suppl_16.ii_832-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Kari S Kaikkonen ◽

Marja-Leena Kortelainen ◽

Heikki V Huikuri

Keyword(s):

Risk Factors ◽

Family History ◽

Sudden Cardiac Death ◽

Cardiac Hypertrophy ◽

Odds Ratio ◽

Cardiac Death ◽

Coronary Event ◽

Acute Coronary Event ◽

Risk Profiles ◽

History Of

Introduction. There is little information on the specific risk factors leading to sudden cardiac death (SCD) during an acute coronary event, because the risk variables may overlap with those of non-fatal coronary event. This study was designed to compare the risk profiles of SCD victims and survivors of an acute coronary event. Methods and Results. A case-control study included consecutive victims of SCD (n=425, mean age 64±11 years) verified to be due to an acute coronary event at medicolegal autopsy and consecutive patients surviving an acute myocardial infarction (AMI, n=644, mean age 62±10 years). Common cardiovascular risk factors, cardiac hypertrophy, and severity of coronary artery disease (CAD) were assessed in both groups. Family history of SCD (odds ratio 1.5, 95% CI 1.0 to 2.2, p=0.03), male gender (odds ratio 1.8, 95% CI 1.3 to 2.4, p<0.001), current smoking (odds ratio 2.0, 95% CI 1.5 to 2.6, p<0.001), cardiac hypertrophy (odds ratio 3.0, 95% CI 2.3 to 3.9, p<0.001) and 3-vessel CAD (odds ratio 5.4, 95% CI 3.6 to 8.2, p<0.001) were more common among the victims of SCD as compared to survivors of AMI. On the contrary, history of hypercholesterolemia (p<0.001) was less common among the SCD victims. There was a cumulative increase of risk of being a SCD victim vs. AMI survivor when more than one risk factor was present, the odds ratio being 44.3 (95% CI 8.0 to 246.7) in a current male smoker with a family history of SCD and cardiac hypertrophy. When 3-vessel CAD was added to the combined risk score, all subjects (7% of the SCD victims) were in the group of SCD giving a 100% sensitivity and specificity, respectively, in differentiating between the SCD victims and AMI survivors. Conclusions. There are specific features that differentiate the victims of SCD from survivors of an acute coronary event. Clustering of several variables, such as family history of SCD, smoking, cardiac hypertrophy, and 3-vessel CAD indicate a very high risk of SCD.

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P1000Aetiology and efficacy of atrial fibrillation ablation in young adults

EP Europace ◽

10.1093/europace/euaa162.001 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

R Zhang ◽

I T Fazmin ◽

A Porto ◽

K Divulwewa ◽

A Reddy ◽

...

Keyword(s):

Atrial Fibrillation ◽

Young Adults ◽

Family History ◽

Sudden Cardiac Death ◽

Pulmonary Vein ◽

Cardiac Death ◽

Univariate Analysis ◽

Pulmonary Vein Stenosis ◽

Af Ablation ◽

History Of

Abstract Introduction Little is known regarding the aetiology or outcome of atrial fibrillation (AF) occurring in young adults. This retrospective analysis was performed to explore the demographics and efficacy of AF ablation in this population. Methods Patients were included who had undergone ≥1 AF ablation under the age of 40 between 2006-2018. Recurrence was defined as return of either documented AF or previous symptoms for >30s following a 3-month blanking period. Initial exploratory co-variates were included in a univariate analysis and those terms with P-value of <0.1 were then used to generate a Cox proportional-hazards multivariate model. Results 124 patients (33.6 ± 4.7 yrs, 77% men), initially presenting with paroxysmal AF (pAF; n = 97) or persistent AF (n = 27), underwent 175 AF ablation procedures. 22.6% (n = 28) also had atrial flutter. Time from symptom onset to first ablation was 50.7 ± 46.2 months. Relevant cardiovascular-related demographics were analysed: hypertension in 8.9% (n = 11); diabetes in 1.6% (n = 2); positive family history of AF in 12.9% (n = 16); and family history of sudden cardiac death in 2.4% (n = 3). Mean CHA2DS2-VASc score was 0.35. Of those patients with documented echocardiogram imaging (n = 91), 26.4% (n = 24) had LA dilatation and 6.6% (n = 6) had LV dysfunction. Patients with LA dilatation underwent more ablations (2.3 ± 0.3) compared to controls (1.5 ± 0.1; p < 0.001). Ablation strategy was pulmonary vein isolation (PVI) only in 67.2% (n = 119), with additional ablation in the remaining: roof line in 18.9% (n = 33); cavotricuspid isthmus line in 13.1% (n = 23); mitral isthmus line in 2.3% (n = 4); superior vena cava isolation in 2.3% (n = 4); complex fractionated atrial electrograms in 14.9% (n = 26). Mean procedure time was 155 ± 41 min, mean ablation time was 1657 ± 991 s and mean fluoroscopy time was 32.6 ± 23.4 min. General anaesthesia was used in 43.4% (n = 76). Complications included femoral haematoma (n = 2), tamponade (n = 1) and pulmonary vein stenosis (n = 2). 90 days of follow-up was available for 137 procedures performed for pAF (n = 105) and persistent AF (n = 32). For pAF, overall recurrence was 61.9% for first ablations and 62.9% overall. Recurrence was 56.3% for persistent AF. Factors significantly associated with increased AF recurrence in univariate analysis were male gender (hazard ratio (HR) 2.3, 95% confidence interval (CI): 1.2-4.4, p = 0.011), hypertension (HR 0.5, CI: 0.2-1.1, p = 0.067), family history of sudden cardiac death (HR 6.8, CI: 1.6-29.0 , p = 0.010) and enlarged LA size (HR 2.2, CI: 1.3-3.6, p = 0.003). In multivariate analysis, the only significant predictor of poor outcome was enlarged LA size (HR 2.0, 95% CI: 1.2-3.5, p = 0.011). Conclusions Young patients with AF may have structurally abnormal hearts, and therefore do not only present with lone AF. LA size may be used as a predictor for success. Surveillance imaging may be useful to detect future structural change, which will be the subject of future prospective studies. Abstract Figure. AF ablation recurrence in young adults

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