The Diagnostic Yield of Brugada Syndrome After Sudden Death With Normal Autopsy

Papadakis, Michael; Papatheodorou, Efstathios; Mellor, Greg; Raju, Hariharan; Bastiaenen, Rachel; Wijeyeratne, Yanushi D.; Wasim, S.; Ensam, Bode; Finocchiaro, Gherardo; Gray, Belinda; Malhotra, Aneil; D’Silva, Andrew; Edwards, Nina M; Cole, Della; Attard, Virginia; Batchvarov, Velislav N.; Esteban, Maria Teresa Tome; Homfray, Tessa; Sheppard, Mary N.; Sharma, Sanjay; Behr, Elijah R.

doi:10.1016/j.jacc.2018.01.031

Cited by 90 publications

(77 citation statements)

References 40 publications

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“…49,50 Papadakis et al demonstrated the clinical utility of high right parasternal leads (HRPL) during the assessment of 911 relatives of probands of SADS and ajmaline challenge in 670 relatives who were without a diagnosis after initial investigations. 36 During initial evaluation, only 4 (0.4%) of relatives had a spontaneous Type 1 pattern (2 of which were only detected using HRPL). 36 Ajmaline testing was required to unmask 97% of the blood relatives eventually diagnosed with BrS.…”

Section: Brugada Syndromementioning

confidence: 99%

“…36 During initial evaluation, only 4 (0.4%) of relatives had a spontaneous Type 1 pattern (2 of which were only detected using HRPL). 36 Ajmaline testing was required to unmask 97% of the blood relatives eventually diagnosed with BrS. 36 The use of HRPLs during ajmaline challenge increased the diagnostic yield by a further 16% (an additional 49 families recognized).…”

Section: Brugada Syndromementioning

confidence: 99%

“…2 More frequent use of exercise stress tests, signal-averaged ECG and provocation testing has improved the diagnostic yield of clinical evaluation. 32,35,36 Some early studies report up to 50% diagnostic yield through the clinical evaluation of surviving family members alone. 2,37,38 Contemporary studies report a lower yield from clinical evaluation alone 9,36,39 and may be attributed to an increase in reporting and referral patterns of cases of SCD for further investigation, creating a more heterogeneous population compared to earlier studies.…”

Section: Emerging Role Of Imagingmentioning

confidence: 99%

“…46 The sensitivity of the ECG diagnosis of Type 1 Brugada pattern can be increased by further steps such as shifting the right precordial leads to higher intercostal spaces (typically 2nd or 3rd) and by procainamide/flecainide/ajmaline challenge. 36,42,43,47 Other factors such as drugs or medications, fever and diurnal variation also increase the prevalence of the Type 1 pattern. 45,47 SCN5A is the most commonly affected gene in BrS but is only affected in around 20% of clinically diagnosed BrS cases.…”

Section: Brugada Syndromementioning

confidence: 99%

“…36 Ajmaline testing was required to unmask 97% of the blood relatives eventually diagnosed with BrS. 36 The use of HRPLs during ajmaline challenge increased the diagnostic yield by a further 16% (an additional 49 families recognized). 36 The use of drug provocation testing is controversial given the high rate (27%) of positive tests in patients with the benign arrhythmia atrioventricular nodal reentrant tachycardia (AVNRT), raising concerns regarding overdiagnosis.…”

Section: Brugada Syndromementioning

confidence: 99%

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<p>Spotlight on sudden arrhythmic death syndrome</p>

Yuan¹,

Raju²

2019

RRCC

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Sudden cardiac death (SCD) is defined as death from a cardiac cause within 1 hr of symptom onset or, if unwitnessed, in a person last seen well within 24 hrs. Sudden arrhythmic death syndrome (SADS) describes cases of SCD with no abnormalities found on expert autopsy attributable as the cause of death. The epidemiology of these conditions has been challenging to study as definitions have changed over time; however, it is apparent that the incidence of SCD increases with age whilst SADS decreases as coronary artery disease becomes more prevalent. Accurate reporting of truly negative autopsies of SCDs has been assisted by guidelines from governing bodies such as The Association for European Cardiovascular Pathology, allowing identification of SADS cases. Primary arrhythmic cardiac conditions like ong QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia are the predominant etiologies of SADS. When the decedent did not have a known phenotype for these conditions, clinical evaluation using screening tests like echocardiogram, resting and stress electrocardiograms and holter monitoring, followed by specialized testing when appropriate such as cardiac magnetic resonance and pharmacological provocation testing of surviving family members becomes crucial in potentially identifying the cause and guide targeted genetic testing. Although advancement in gene analysis such as next-generation sequencing has also allowed the application of "molecular autopsy" to identify pathogenic variants to establish the cause of death and enable cascade testing and risk stratification of family members, many of the genetic variants identified through this method have been classified as non-pathogenic since the establishment of standards and guidelines by the American College of Medical Genetics. Whilst majority of cases of SADS are still unexplained, there is increasing awareness and understanding of this syndrome allowing appropriate identification of surviving family members at risk and implementation of measures to prevent further premature death.

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Section: Brugada Syndromementioning

confidence: 99%

Section: Brugada Syndromementioning

confidence: 99%

Section: Emerging Role Of Imagingmentioning

confidence: 99%

Section: Brugada Syndromementioning

confidence: 99%

Section: Brugada Syndromementioning

confidence: 99%

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<p>Spotlight on sudden arrhythmic death syndrome</p>

Yuan¹,

Raju²

2019

RRCC

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2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families

Stiles

Wilde

Abrams

et al. 2021

Journal of Arrhythmia

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This international multidisciplinary document intends to provide clinicians with evidence‐based practical patient‐centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.

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