Genetic Testing in the Evaluation of Unexplained Cardiac Arrest

Mellor, Greg; Laksman, Zachary; Tadros, Rafik; Roberts, Jason D.; Gerull, Brenda; Simpson, Christopher S.; Klein, George J.; Champagne, Jean; Talajic, Mario; Gardner, Martin J.; Steinberg, Christian; Arbour, Laura; Birnie, David H.; Angaran, Paul; Leather, Richard; Sanatani, Shubhayan; Chauhan, Vijay S.; Seifer, Colette; Healey, Jeffrey S.; Krahn, Andrew D.

doi:10.1161/circgenetics.116.001686

Cited by 77 publications

(47 citation statements)

References 25 publications

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“… 12 , 43 Secondly, because patients with SCA and no structural heart disease most of the time turn out to have inherited cardiac disorders, obtaining a diagnosis is crucial to perform targeted screening of family members, allowing early diagnosis and implementation of primary prevention for these patients, before the potential occurrence of a life-threatening event as first presentation. 5 , 8 , 10 , 11 , 44 , 45 …”

Section: Discussionmentioning

confidence: 99%

“…The value of genetic tests has also been emphasized in case of clinical suspicion of a specific phenotype with an inherited cardiac disorder. 12 Although targeted genetic testing has been reported to find causative mutations in up to almost 50% of cases of apparently unexplained SCA, 11 genetic screening for a large panel of genes in IVF patients is not currently recommended, 12 , 43 due to its low yield in the absence of a specific clinical suspicion to guide testing, where multiple rare variants of unknown significance cannot formally be considered as causal in the absence of informative familial analyses. Nevertheless, being initiated in only 9 (18.4%) patients in the present study, there is a clear, present scope to enhance the role of genetic testing in the diagnostic armamentarium, particularly in the light of promising results from recent studies.…”

Section: Discussionmentioning

confidence: 99%

“… 14 – 16 This is crucial from several perspectives including prognostication, implementation of specific therapy when possible, appropriate lifestyle counselling, and also optimization of screening and prevention among relatives. 5 , 8 , 10 , 11 , 17 , 18 …”

Section: Introductionmentioning

confidence: 99%

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Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation

Waldmann

Bougouin

Karam

et al. 2018

European Heart Journal

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AimsRecent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown.Methods and resultsData were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80–22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12–12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively.ConclusionOur findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation

Waldmann

Bougouin

Karam

et al. 2018

European Heart Journal

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“…CASPER has been an important registry in the field of cardio-genetics. It has led to numerous publications pertaining to IHRD, and now includes an enrollment exceeding 1200 patients (Herman et al 2016;Mellor et al 2017;Somani et al 2014;Steinberg et al 2016;Vittoria Matassini et al 2014). In the present study, we recruited participants from the initial HiRO/CASPER membership, and through web-based searches of the 17 Canadian universities with medical schools, and by contacting administrators from the seven established IHRD clinics in Canada.…”

Section: Methodsmentioning

confidence: 99%

The accessibility and utilization of genetic testing for inherited heart rhythm disorders: a Canadian cross-sectional survey study

et al. 2017

Self Cite

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The genetic basis of many sudden death-related conditions has been elucidated. These include inherited arrhythmias and arrhythmogenic cardiomyopathies, termed inherited heart rhythm disorders (IHRD). Advising on and interpreting genetic testing is challenging for the general cardiologist. This has led to the development of interdisciplinary clinics for IHRD in varying stages of establishment in Canada. We sought the viewpoints and patterns of practice of Canadian IHRD experts, and assessed their ability to access genetic testing for IHRD using a national cross-sectional survey. Of 56 participants, most were physicians (68%) or genetic counselors (19%). Despite working collaboratively, most genetic counselors (59%) were either not satisfied or only somewhat satisfied with their relationships with physicians. Ninety percent of participants were involved in offering genetic evaluation, including 80% who felt that testing was usually/always accessible. Most offered genetic testing to confirm clinical diagnosis and/or direct family screening. Post-mortem genetic analysis was sought by 69% of respondents; however, a lack of retained tissue and/or poor tissue preparation hindered this process. Family screening was usually recommended in the setting of a pathogenic/likely pathogenic variant. The most commonly perceived barrier to genetic testing was cost to the healthcare system. More than a quarter of patients waited ≥ 6 months for funding. An ability to engage at-risk relatives was rated as limited/poor by 34% of participants. Despite the establishment of several interdisciplinary clinics, timely access to affordable testing, supported by strong team communication, continues to be a barrier to genetic testing in Canada.

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“…The identification of the substrate of idiopathic ventricular fibrillation (VF) in the absence of structural heart disease or electrocardiographic changes remains a challenge for patient management and family counseling. The availability of expanded genetic testing panels and clinical exome screening has not led to a significant increase in the identification of genetic causes of these events, as shown by recent reports 1, 2. Indeed, the majority of studies detected only a small number of genetic variants1, 2 that could explain a sudden cardiac arrest event.…”

Section: Introductionmentioning

confidence: 99%