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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

  • Author Footnotes
    ˆ Martin K. Stiles, MBChB, PhD, FHRS, and Arthur A. M. Wilde, MD, PhD, are co-first authors.
    Martin K. Stiles
    Footnotes
    ˆ Martin K. Stiles, MBChB, PhD, FHRS, and Arthur A. M. Wilde, MD, PhD, are co-first authors.
    Affiliations
    Waikato Clinical School, Faculty of Medicine and Health Science, The University of Auckland, Hamilton, New Zealand
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  • Author Footnotes
    ˆ Martin K. Stiles, MBChB, PhD, FHRS, and Arthur A. M. Wilde, MD, PhD, are co-first authors.
    ,
    Author Footnotes
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    ,
    Author Footnotes
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Arthur A.M. Wilde
    Footnotes
    ˆ Martin K. Stiles, MBChB, PhD, FHRS, and Arthur A. M. Wilde, MD, PhD, are co-first authors.
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Affiliations
    Amsterdam University Medical Center, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam, the Netherlands
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  • Author Footnotes
    ∗ Representative of the Pediatric and Congenital Electrophysiology Society (PACES)
    Dominic J. Abrams
    Footnotes
    ∗ Representative of the Pediatric and Congenital Electrophysiology Society (PACES)
    Affiliations
    Boston Children’s Hospital, Boston, Massachusetts, USA
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  • Author Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Michael J. Ackerman
    Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Affiliations
    Mayo Clinic, Rochester, Minnesota, USA
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  • Author Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Christine M. Albert
    Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Affiliations
    Cedars-Sinai Medical Center, Los Angeles, California, USA
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  • Author Footnotes
    ‡ Representative of the European Heart Rhythm Association (EHRA)
    ,
    Author Footnotes
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    ,
    Author Footnotes
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Elijah R. Behr
    Footnotes
    ‡ Representative of the European Heart Rhythm Association (EHRA)
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Affiliations
    Cardiovascular Clinical Academic Group, Molecular and Clinical Sciences Institute, St George’s, University of London, and St George’s University Hospitals NHS Foundation Trust, London, United Kingdom
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  • Author Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Sumeet S. Chugh
    Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Affiliations
    Cedars-Sinai Medical Center, Los Angeles, California, USA
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  • Author Footnotes
    § Representative of the European Society of Human Genetics (ESHG)
    Martina C. Cornel
    Footnotes
    § Representative of the European Society of Human Genetics (ESHG)
    Affiliations
    Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Clinical Genetics, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
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  • Author Footnotes
    Δ Patient representative
    Karen Gardner
    Footnotes
    Δ Patient representative
    Affiliations
    University of New South Wales, Canberra, Australia
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  • Author Footnotes
    # Representative of the National Society of Genetic Counselors (NSGC)
    Jodie Ingles
    Footnotes
    # Representative of the National Society of Genetic Counselors (NSGC)
    Affiliations
    Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, Australia
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  • Author Footnotes
    # Representative of the National Society of Genetic Counselors (NSGC)
    Cynthia A. James
    Footnotes
    # Representative of the National Society of Genetic Counselors (NSGC)
    Affiliations
    Johns Hopkins University, Baltimore, Maryland, USA
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  • Author Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Jyh-Ming Jimmy Juang
    Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Affiliations
    Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
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  • Author Footnotes
    ‡ Representative of the European Heart Rhythm Association (EHRA)
    ,
    Author Footnotes
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    Stefan Kääb
    Footnotes
    ‡ Representative of the European Heart Rhythm Association (EHRA)
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    Affiliations
    Department of Medicine I, University Hospital, LMU Munich, Munich, Germany
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  • Author Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Elizabeth S. Kaufman
    Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Affiliations
    MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio, USA
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  • Author Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Andrew D. Krahn
    Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Affiliations
    The University of British Columbia, Vancouver, British Columbia, Canada
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  • Author Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Steven A. Lubitz
    Footnotes
    † Representative of the Heart Rhythm Society (HRS)
    Affiliations
    Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Author Footnotes
    # Representative of the National Society of Genetic Counselors (NSGC)
    Heather MacLeod
    Footnotes
    # Representative of the National Society of Genetic Counselors (NSGC)
    Affiliations
    Data Coordinating Center for the Sudden Death in the Young Case Registry, Okemos, Michigan, USA
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  • Author Footnotes
    ∗∗ Representative of the Latin American Heart Rhythm Society (LAHRS)
    Carlos A. Morillo
    Footnotes
    ∗∗ Representative of the Latin American Heart Rhythm Society (LAHRS)
    Affiliations
    Libin Cardiovascular Institute, Calgary, Alberta, Canada
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  • Author Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Koonlawee Nademanee
    Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Affiliations
    Chulalongkorn University, Faculty of Medicine, and Pacific Rim Electrophysiology Research Institute at Bumrungrad Hospital, Bangkok, Thailand
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  • Author Footnotes
    ‡ Representative of the European Heart Rhythm Association (EHRA)
    ,
    Author Footnotes
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    ,
    Author Footnotes
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Vincent Probst
    Footnotes
    ‡ Representative of the European Heart Rhythm Association (EHRA)
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Affiliations
    CHU de Nantes, Nantes, France
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  • Author Footnotes
    ∗ Representative of the Pediatric and Congenital Electrophysiology Society (PACES)
    Elizabeth V. Saarel
    Footnotes
    ∗ Representative of the Pediatric and Congenital Electrophysiology Society (PACES)
    Affiliations
    Cleveland Clinic Lerner College of Cardiology at Case Western Reserve University, Cleveland, Ohio, and St Luke’s Medical Center, Boise, Idaho, USA
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  • Author Footnotes
    ∗∗ Representative of the Latin American Heart Rhythm Society (LAHRS)
    Luciana Sacilotto
    Footnotes
    ∗∗ Representative of the Latin American Heart Rhythm Society (LAHRS)
    Affiliations
    Heart Institute, University of São Paulo Medical School, São Paulo, Brazil
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  • Author Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Christopher Semsarian
    Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Affiliations
    Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, Australia
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  • Author Footnotes
    †† Representative of the Association for European Cardiovascular Pathology (AECVP)
    ,
    Author Footnotes
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Mary N. Sheppard
    Footnotes
    †† Representative of the Association for European Cardiovascular Pathology (AECVP)
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Affiliations
    Cardiovascular Clinical Academic Group, Molecular and Clinical Sciences Institute, St George’s, University of London, and St George’s University Hospitals NHS Foundation Trust, London, United Kingdom
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  • Author Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Wataru Shimizu
    Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Affiliations
    Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
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  • Author Footnotes
    ∗ Representative of the Pediatric and Congenital Electrophysiology Society (PACES)
    Jonathan R. Skinner
    Footnotes
    ∗ Representative of the Pediatric and Congenital Electrophysiology Society (PACES)
    Affiliations
    Cardiac Inherited Disease Group, Starship Hospital, Auckland, New Zealand
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  • Author Footnotes
    ‡ Representative of the European Heart Rhythm Association (EHRA)
    ,
    Author Footnotes
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    ,
    Author Footnotes
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Jacob Tfelt-Hansen
    Footnotes
    ‡ Representative of the European Heart Rhythm Association (EHRA)
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Affiliations
    Department of Forensic Medicine, Faculty of Medical Sciences, Rigshospitalet, Copenhagen, Denmark
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  • Author Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Dao Wu Wang
    Footnotes
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    Affiliations
    The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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  • Author Footnotes
    ∗ Representative of the Pediatric and Congenital Electrophysiology Society (PACES)
    † Representative of the Heart Rhythm Society (HRS)
    ‡ Representative of the European Heart Rhythm Association (EHRA)
    § Representative of the European Society of Human Genetics (ESHG)
    ¶ Representative of the Asia Pacific Heart Rhythm Society (APHRS)
    # Representative of the National Society of Genetic Counselors (NSGC)
    ∗∗ Representative of the Latin American Heart Rhythm Society (LAHRS)
    †† Representative of the Association for European Cardiovascular Pathology (AECVP)
    ¥ Member of the European Cardiac Arrhythmia Genetics (ECGen) Focus Group of the European Heart Rhythm Association (EHRA)
    II Member of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart
    Δ Patient representative
    ˆ Martin K. Stiles, MBChB, PhD, FHRS, and Arthur A. M. Wilde, MD, PhD, are co-first authors.
Open AccessPublished:October 19, 2020DOI:https://doi.org/10.1016/j.hrthm.2020.10.010

      Abstract

      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.

      Keywords

      Abbreviations:

      AED (automated external defibrillator), CIED (cardiovascular implantable electronic device), CMR (cardiac magnetic resonance imaging), COR (Class of Recommendation), CPR (cardiopulmonary resuscitation), CPVT (catecholaminergic polymorphic ventricular tachycardia), CT (computed tomography), ECG (electrocardiogram), EMS (emergency medical services), LOE (Level of Evidence), MRI (magnetic resonance imaging), OHCA (out-of-hospital cardiac arrest), PVC (premature ventricular complex), RWI (relationship with industry and other entities), SAD(S) (sudden arrhythmic death (syndrome)), SCA (sudden cardiac arrest), SCD (sudden cardiac death), SUD (sudden unexplained death)
      Document Reviewers: Takeshi Aiba, MD, PhD; Allison L. Cirino, MS, CGC; Florence Fellmann, MD, PhD; Michael H. Gollob, MD; Yung-Kuo Lin, MD, PhD; Joaquín S. Lucena, MD, PhD; Ciorsti MacIntyre, MD; Jens Cosedis Nielsen, MD, DMSc, PhD, FESC, FEHRA; Juan David Ramirez, MD; Gregory Webster, MD, MPH, CCDS

      Top 10 Take-Home Messages

      • 1.
        Sudden cardiac death (SCD) is an important public health issue and warrants further study to better quantify its occurrence, its impact on society, and the opportunities for improving outcomes through public education and provision of automated external defibrillators and cardiopulmonary resuscitation (CPR) training.
      • 2.
        For survivors of sudden cardiac arrest (SCA), victims of sudden unexplained death (SUD), and their relatives, a multidisciplinary team is central to thorough investigation, so as to maximize the opportunity to make a diagnosis. Where there has been an SCD or resuscitated SCA and a genetic cause is suspected, genetic testing and counseling is essential for families, to ensure that risks, benefits, results, and the clinical significance of genetic testing can be discussed.
      • 3.
        The psychological care of families affected by SUD and survivors of SCA (and their families) should run in parallel with the investigation process. Assessment by professionals trained in psychological care should be offered, as well as grief counseling and peer support, where appropriate.
      • 4.
        For the investigation of SUD, a detailed personal and family history is essential, with attention to sentinel symptoms during life such as syncope or seizures, witness accounts, premorbid investigations, and inspection of any cardiac rhythm monitoring around the time of death.
      • 5.
        A comprehensive autopsy is an essential part of the investigation of SUD and should include collection and storage of tissue suitable for genetic analysis. When the autopsy suggests a possible genetic cause, or no cause and the heart is normal, referral to a multidisciplinary team for further investigation is indicated.
      • 6.
        For victims of SCD or survivors of cardiac arrest where the phenotype is known, genetic testing of the proband focused on likely candidate genes, along with clinical evaluation of family members, aids in identifying family members with, or at risk of developing, the same condition.
      • 7.
        For victims of SCD or survivors of cardiac arrest where the phenotype is not known, arrhythmia syndrome–focused genetic testing may help arrive at a secure diagnosis, whereas wider testing without careful consideration of the implications of indeterminate results by experienced clinicians may only serve to add uncertainty and lead to misinterpretation of results.
      • 8.
        For the investigation of SCA survivors, essential inquiry includes detailed personal and family history, witness accounts, physical examination, multiple electrocardiograms (ECGs), and cardiac imaging. Ambulatory monitoring and/or provocative testing (exercise, pharmacological, and invasive electrophysiological) may provide additional useful information. A sample suitable for future DNA testing should be taken early in the patient’s course and stored.
      • 9.
        Genetic investigation of SCA survivors is best undertaken at a center with multidisciplinary care infrastructure and should focus on likely candidate genes known to be causally related to the suspected phenotype. In some cases, genetic evaluation without a suspected phenotype may be undertaken with appropriate genetic counseling, although genetic evaluation of patients with a known nongenetic cause of cardiac arrest is discouraged.
      • 10.
        The investigation of the families of victims of SUD and survivors of SCA should include clinical and, if known, genetic cascade testing. If the cause of SUD (or rarely, SCA) is unknown, then clinical investigation of first-degree relatives may include physical examination, ECGs, cardiac imaging, ambulatory monitoring, and provocative testing (exercise, pharmacological, and rarely invasive electrophysiological) with multidisciplinary team supervision. Follow-up and periodic re-evaluation are important and are directed by initial findings.

      Section 1 Introduction

      1.1 Purpose

      This expert consensus statement represents an international multidisciplinary effort led by the Asia Pacific Heart Rhythm Society (APHRS), in partnership with the Heart Rhythm Society (HRS) and in collaboration with the Association for European Cardiovascular Pathology (AECVP), the European Heart Rhythm Association (EHRA), the European Society of Human Genetics (ESHG), the Latin American Heart Rhythm Society (LAHRS), the National Society of Genetic Counselors (NSGC) (USA), the Pediatric and Congenital Electrophysiology Society (PACES), and the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart. The intent is to provide clinicians with practical patient-centered recommendations for evaluating patients with sudden cardiac arrest (SCA), decedents with sudden cardiac death (SCD), and their families, based on all available evidence. Although the recommendations are for optimal care, the writing committee recognizes that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide.

      1.2 Organization of the Writing Committee

      The writing committee consisted of internationally recognized experts from 14 countries in the fields of cardiac electrophysiology, cardiology, pediatric cardiology, genetic counseling, community genetics and public health genomics, and cardiac pathology, representing APHRS, HRS, AECVP, EHRA, ESHG, LAHRS, NSGC, PACES, and ERN GUARD-Heart and selected according to each society’s procedures. In addition, a patient representative was chosen to provide a consumer viewpoint. Each partner society nominated a chair, who did not have relevant relationships with industry and other entities (RWIs). In accordance with the APHRS policies, disclosure of any RWIs was required from the writing committee members (Appendix 1) and from the peer reviewers (Appendix 2); of the 28 committee members, 23 (82%) had no relevant RWIs. Recommendations were drafted by the writing committee members who did not have relevant RWIs.

      1.3 Methodology and Evidence Review

      After development of a preliminary outline, committee members were given writing assignments and a schedule of conference calls. Writing committee members conducted a comprehensive evidence search using MEDLINE/PubMed, Embase, and the Cochrane Library and summarized the evidence in standardized tables (Appendix 3), with attention to the study type, size, inclusion criteria, and key findings. The writing committee reviewed evidence and established consensus to generate recommendations, which are presented in a modular knowledge chunk format, with each chunk including a table of recommendations, a brief synopsis, recommendation-specific supportive text, flow diagrams or tables as appropriate, and references. Recommendations were formulated according to the American College of Cardiology (ACC)/American Heart Association (AHA) Class of Recommendation (COR) and Level of Evidence (LOE) system
      • Halperin J.L.
      • Levine G.N.
      • Al-Khatib S.M.
      • et al.
      Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      (Table 1) and were subject to a period of public comment. The COR indicates the strength of a recommendation based on assessment of the estimated benefits and risks; LOE rates the quality of evidence that supports the recommendation based on type, quantity, and consistency of data from clinical trials and other sources. Case reports were not used to support recommendations. The threshold for consensus was considered as 80% or higher agreement. The 74 recommendations were balloted by the 28 writing committee members and approved by an average of 94%. A quorum of two-thirds of the writing committee was met for all votes.
      Table 1ACC/AHA recommendation system: Applying Class of Recommendation and Level of Evidence to clinical strategies, interventions, treatments, and diagnostic testing in patient care∗
      Reprinted with permission from the American College of Cardiology (ACC) and the American Heart Association (AHA).

      1.4 Document Review and Approval

      After review by the entire writing committee, the recommendations were opened for public comment; the draft document was reviewed by the International Scientific Document Writing Committee of the APHRS and the Scientific and Clinical Documents Committee of the HRS and was revised prior to external review. The document underwent external peer review by reviewers appointed by the APHRS and HRS and each of the collaborating societies. After subsequent revisions and endorsement by the participating societies, the document was ready for publication.

      1.5 Scope of the Document

      This document provides a framework for the investigation of 1) patients with SCA, 2) decedents with sudden unexplained death (SUD), and 3) families of both SCA survivors and SUD victims, as many conditions responsible for the cardiac arrest or unexplained death may be familial. Identifying a cause is important for preventing further events in the family, should an inherited condition be found. Integral to the process is the 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 the futures of the family members. The disciplines of cardiology, pediatrics, radiology, pathology, counseling, psychology, and genetics are all involved in this process. Therefore, the formation of multidisciplinary teams is essential to provide a complete service to the patients and their families.
      While this document endeavors to provide clinicians with practical recommendations for evaluating patients with SCA, decedents with SUD, and their families, the best approach will vary with the situation and will be influenced by, for example, the subject’s age and results of initial testing. Although some of the recommendations do specify an age cutoff, it is recognized that this age is somewhat arbitrary and may not be always appropriate for the disease being investigated for or the demographics of the patient’s country. Nevertheless, where an age is specified in a recommendation, it has passed the consensus voting of the writing group. Referral to a center with a multidisciplinary team experienced in such evaluations is recommended because it can facilitate navigation of these complexities. A multidisciplinary team can also help organize interval follow-up evaluations for SCA survivors and their family members. Repeated interval follow-up can reveal important new clinical data and allows for integration of new knowledge into the continued evaluation and care of these patients. The writing committee members recognize that not all investigative modalities recommended will be available in all circumstances; however, this document is an attempt to outline an approach to which the clinician should aspire.

      1.6 Relevant Clinical Practice Documents

      Table 2 lists pertinent guidelines and consensus statements that the writing committee considered for this document. The included documents contain relevant information for the diagnosis of patients with SCA and SCD.
      Table 2Relevant clinical practice documents
      TitlePublication year
      European Recommendations Integrating Genetic Testing into Multidisciplinary Management of Sudden Cardiac Death
      • Fellmann F.
      • van El C.G.
      • Charron P.
      • et al.
      European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death.
      2019
      2019 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias
      • Cronin E.M.
      • Bogun F.M.
      • Maury P.
      • et al.
      2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias.
      2019
      2019 HRS Expert Consensus Statement on Evaluation, Risk Stratification, and Management of Arrhythmogenic Cardiomyopathy
      • Towbin J.A.
      • McKenna W.J.
      • Abrams D.J.
      • et al.
      2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.
      2019
      2018 ESC Guidelines for the Diagnosis and Management of Syncope
      • Brignole M.
      • Moya A.
      • de Lange F.J.
      • et al.
      2018 ESC guidelines for the diagnosis and management of syncope.
      2018
      2017 AHA/ACC/HRS Guideline for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death
      • Al-Khatib S.M.
      • Stevenson W.G.
      • Ackerman M.J.
      • et al.
      2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death.
      2017
      Pre-participation Cardiovascular Evaluation for Athletic Participants to Prevent Sudden Death: Position Paper from the EHRA and the EACPR, Branches of the ESC
      • Mont L.
      • Pelliccia A.
      • Sharma S.
      • et al.
      Pre-participation cardiovascular evaluation for athletic participants to prevent sudden death: position paper from the EHRA and the EACPR, branches of the ESC.
      2016
      2015 ESC Guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death
      • Priori S.G.
      • Blomstrom-Lundqvist C.
      • Mazzanti A.
      • et al.
      2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death.
      2015
      EHRA/HRS/APHRS Expert Consensus on Ventricular Arrhythmias
      • Pedersen C.T.
      • Kay G.N.
      • Kalman J.
      • et al.
      EHRA/HRS/APHRS expert consensus on ventricular arrhythmias.
      2014
      HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes
      • Priori S.G.
      • Wilde A.A.
      • Horie M.
      • et al.
      HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.
      2013
      HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies
      • Ackerman M.J.
      • Priori S.G.
      • Willems S.
      • et al.
      HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies.
      2011

      1.7 Definitions

      The terms used in the consensus statement are defined in Table 3.
      Table 3Definitions
      TermDefinition
      Sudden cardiac arrest (SCA)Sudden cessation of cardiac activity with hemodynamic collapse, typically due to sustained ventricular arrhythmia
      Sudden cardiac death (SCD)Death that occurs within 1 hour of onset of symptoms in witnessed cases, and within 24 hours of last being seen alive when it is unwitnessed
      Sudden unexplained death (syndrome) (SUD[S])Unexplained sudden death occurring in an individual older than 1 year
      Sudden unexplained death in infancy (SUDI)Unexplained sudden death occurring in an individual younger than 1 year with negative pathological and toxicological assessment

      Note: Synonymous with “sudden unexplained infant death” (SUID)
      Sudden arrhythmic death (syndrome) (SAD[S])Unexplained sudden death occurring in an individual older than 1 year with negative pathological and toxicological assessment

      Note: Synonymous with “autopsy-negative sudden unexplained death”
      Sudden unexplained death in epilepsy (SUDEP)Sudden and unexpected, nontraumatic and nondrowning death of a person with epilepsy, without a toxicological or anatomical cause of death detected during the postmortem examination

      Section 2 Epidemiology

      2.1 Epidemiology: Sudden Death

      "Sudden unexplained death" refers to an unexpected and sudden death in an individual older than 1 year. Sudden death occurring unexpectedly within the first year of life is termed “sudden unexplained death in infancy” (SUDI). Multiple definitions have been in use over the past decades, although most recent studies implement a definition that differs between witnessed and unwitnessed events; in witnessed cases, death has to occur within 1 hour of change in cardiovascular status, whereas unwitnessed cases have to be seen alive and functioning normally within 24 hours of being found dead.
      • Zipes D.P.
      • Camm A.J.
      • Borggrefe M.
      • et al.
      ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death).
      ,
      • Fishman G.I.
      • Chugh S.S.
      • Dimarco J.P.
      • et al.
      Sudden cardiac death prediction and prevention: report from a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop.
      SCD constitutes the majority of SUD.
      • Risgaard B.
      • Lynge T.H.
      • Wissenberg M.
      • et al.
      Risk factors and causes of sudden noncardiac death: a nationwide cohort study in Denmark.
      • Winkel B.G.
      • Holst A.G.
      • Theilade J.
      • et al.
      Nationwide study of sudden cardiac death in persons aged 1-35 years.
      • Sanchez O.
      • Campuzano O.
      • Fernandez-Falgueras A.
      • et al.
      Natural and undetermined sudden death: value of post-mortem genetic investigation.
      Reported overall SCD incidence rates vary across studies and countries, in part due to large difference in SCD definitions and methods for estimation of SCD rates. Previous studies report overall SCD rates ranging from 15 to 159 SCD per 100,000 persons per annum, corresponding to 6–20% of all deaths.
      • Nichol G.
      • Thomas E.
      • Callaway C.W.
      • et al.
      Regional variation in out-of-hospital cardiac arrest incidence and outcome.
      • Chugh S.S.
      • Jui J.
      • Gunson K.
      • et al.
      Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.
      • de Vreede-Swagemakers J.J.
      • Gorgels A.P.
      • Dubois-Arbouw W.I.
      • et al.
      Out-of-hospital cardiac arrest in the 1990's: a population-based study in the Maastricht area on incidence, characteristics and survival.
      • Stecker E.C.
      • Reinier K.
      • Marijon E.
      • et al.
      Public health burden of sudden cardiac death in the United States.
      • Wong C.X.
      • Brown A.
      • Lau D.H.
      • et al.
      Epidemiology of sudden cardiac death: global and regional perspectives.
      • Kong M.H.
      • Fonarow G.C.
      • Peterson E.D.
      • et al.
      Systematic review of the incidence of sudden cardiac death in the United States.
      • Kitamura T.
      • Iwami T.
      • Kawamura T.
      • et al.
      Nationwide improvements in survival from out-of-hospital cardiac arrest in Japan.
      • Gillum R.F.
      Sudden coronary death in the United States: 1980-1985.
      However, both incidence and causes of SCD vary markedly with age. Lowest SCD incidence is observed in children and adolescents.
      • Winkel B.G.
      • Holst A.G.
      • Theilade J.
      • et al.
      Nationwide study of sudden cardiac death in persons aged 1-35 years.
      ,
      • Chugh S.S.
      • Jui J.
      • Gunson K.
      • et al.
      Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.
      ,
      • Bagnall R.D.
      • Weintraub R.G.
      • Ingles J.
      • et al.
      A prospective study of sudden cardiac death among children and young adults.
      • Wisten A.
      • Krantz P.
      • Stattin E.L.
      Sudden cardiac death among the young in Sweden from 2000 to 2010: an autopsy-based study.
      • Risgaard B.
      • Winkel B.G.
      • Jabbari R.
      • et al.
      Burden of sudden cardiac death in persons aged 1 to 49 years: nationwide study in Denmark.
      • Byrne R.
      • Constant O.
      • Smyth Y.
      • et al.
      Multiple source surveillance incidence and aetiology of out-of-hospital sudden cardiac death in a rural population in the West of Ireland.
      SCD incidence is low in children and the young under 35 years and increases dramatically up until the age of approximately 60–80 years.
      • Winkel B.G.
      • Holst A.G.
      • Theilade J.
      • et al.
      Nationwide study of sudden cardiac death in persons aged 1-35 years.
      ,
      • de Vreede-Swagemakers J.J.
      • Gorgels A.P.
      • Dubois-Arbouw W.I.
      • et al.
      Out-of-hospital cardiac arrest in the 1990's: a population-based study in the Maastricht area on incidence, characteristics and survival.
      ,
      • Stecker E.C.
      • Reinier K.
      • Marijon E.
      • et al.
      Public health burden of sudden cardiac death in the United States.
      ,
      • Winkel B.G.
      • Risgaard B.
      • Sadjadieh G.
      • Bundgaard H.
      • Haunso S.
      • Tfelt-Hansen J.
      Sudden cardiac death in children (1-18 years): symptoms and causes of death in a nationwide setting.
      ,
      • Burns K.M.
      • Cottengim C.
      • Dykstra H.
      • et al.
      Epidemiology of sudden death in a population-based study of infants and children.
      In young persons aged 1–35 years, most SCDs are caused by potentially inherited heart diseases, including primary arrhythmogenic disorders (eg, congenital long QT syndrome and catecholaminergic polymorphic ventricular tachycardia [CPVT]), hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, and dilated cardiomyopathy;
      • Winkel B.G.
      • Holst A.G.
      • Theilade J.
      • et al.
      Nationwide study of sudden cardiac death in persons aged 1-35 years.
      ,
      • Chugh S.S.
      • Jui J.
      • Gunson K.
      • et al.
      Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.
      ,
      • Bagnall R.D.
      • Weintraub R.G.
      • Ingles J.
      • et al.
      A prospective study of sudden cardiac death among children and young adults.
      • Wisten A.
      • Krantz P.
      • Stattin E.L.
      Sudden cardiac death among the young in Sweden from 2000 to 2010: an autopsy-based study.
      • Risgaard B.
      • Winkel B.G.
      • Jabbari R.
      • et al.
      Burden of sudden cardiac death in persons aged 1 to 49 years: nationwide study in Denmark.
      • Byrne R.
      • Constant O.
      • Smyth Y.
      • et al.
      Multiple source surveillance incidence and aetiology of out-of-hospital sudden cardiac death in a rural population in the West of Ireland.
      • Winkel B.G.
      • Risgaard B.
      • Sadjadieh G.
      • Bundgaard H.
      • Haunso S.
      • Tfelt-Hansen J.
      Sudden cardiac death in children (1-18 years): symptoms and causes of death in a nationwide setting.
      ,
      • Eckart R.E.
      • Shry E.A.
      • Burke A.P.
      • et al.
      Sudden death in young adults: an autopsy-based series of a population undergoing active surveillance.
      ,
      • Thiene G.
      • Corrado D.
      • Basso C.
      The Northeast Italy, Veneto Region experience.
      however, coronary artery disease, anomalous coronary arteries, aortic dissection, congenital heart disease, and myocarditis are also potential causes, potentially with a non-negligible genetic component (Figure 1). From the age of 35 years, coronary artery disease becomes the most common cause of SCD, although potentially inherited heart diseases remain a common cause of SCD at least until the age of 50 years.
      • Risgaard B.
      • Winkel B.G.
      • Jabbari R.
      • et al.
      Burden of sudden cardiac death in persons aged 1 to 49 years: nationwide study in Denmark.
      ,
      • Winkel B.G.
      • Risgaard B.
      • Sadjadieh G.
      • Bundgaard H.
      • Haunso S.
      • Tfelt-Hansen J.
      Sudden cardiac death in children (1-18 years): symptoms and causes of death in a nationwide setting.
      ,
      • Chappex N.
      • Schlaepfer J.
      • Fellmann F.
      • Bhuiyan Z.A.
      • Wilhelm M.
      • Michaud K.
      Sudden cardiac death among general population and sport related population in forensic experience.
      Individuals with SUD who subsequently have negative pathological and toxicological assessment may be assumed to have sudden arrhythmic death (syndrome), or SAD(S), a term synonymous with “autopsy-negative SUD.”
      Figure thumbnail gr1
      Figure 1Distribution of causes of death among autopsied cases of sudden cardiac death (n = 753) according to age in persons aged 1–49 years in Denmark (J.T.-H., unpublished data). SADS = sudden arrhythmic death syndrome. ∗Coronary artery disease, especially in young persons, may be due to inherited disease (eg, familial hypercholesterolemia).
      At any age, males have higher SCD rates compared with females, even after adjustment for risk factors of coronary heart disease.
      • Deo R.
      • Albert C.M.
      Epidemiology and genetics of sudden cardiac death.
      Ethnic background seems to have large effect.
      • Becker L.B.
      • Han B.H.
      • Meyer P.M.
      • et al.
      Racial differences in the incidence of cardiac arrest and subsequent survival: the CPR Chicago Project.
      ,
      • Zhao D.
      • Post W.S.
      • Blasco-Colmenares E.
      • et al.
      Racial differences in sudden cardiac death.
      Tabled 1Recommendations for improving outcomes from sudden death
      CORLOERecommendationsReferences
      1B-NR
      • 1.
        Investigation of SUD at a young age should be made a public health priority due to the combined prevalence of inherited cardiac diseases of at least 1:500, the years of potential life lost, and the significant impact on the family and community; therefore, public funding should be allocated for relevant investigations.
      • Winkel B.G.
      • Holst A.G.
      • Theilade J.
      • et al.
      Nationwide study of sudden cardiac death in persons aged 1-35 years.
      ,
      • Bagnall R.D.
      • Weintraub R.G.
      • Ingles J.
      • et al.
      A prospective study of sudden cardiac death among children and young adults.
      ,
      • Behr E.R.
      • Casey A.
      • Sheppard M.
      • et al.
      Sudden arrhythmic death syndrome: a national survey of sudden unexplained cardiac death.
      1C-EO
      • 2.
        Identification of inherited cardiac conditions that predispose to SCD should be made a public health priority, as diagnosis may prevent future cardiac events in affected family members.
      1B-NR
      • 3.
        The burden of SUD and varied outcomes in relation to sex, different ethnic populations, and socioeconomic backgrounds should be investigated worldwide.
      • Becker L.B.
      • Han B.H.
      • Meyer P.M.
      • et al.
      Racial differences in the incidence of cardiac arrest and subsequent survival: the CPR Chicago Project.
      ,
      • Zhao D.
      • Post W.S.
      • Blasco-Colmenares E.
      • et al.
      Racial differences in sudden cardiac death.
      ,
      • Griffis H.
      • Wu L.
      • Naim M.Y.
      • et al.
      Characteristics and outcomes of AED use in pediatric cardiac arrest in public settings: the influence of neighborhood characteristics.
      ,
      • Starks M.A.
      • Schmicker R.H.
      • Peterson E.D.
      • et al.
      Association of neighborhood demographics with out-of-hospital cardiac arrest treatment and outcomes: where you live may matter.
      Synopsis
      SUD is a tragedy and, in the case of an underlying genetic predisposition, may be preventable. The main cause of SUD is SCD. SCD in the young often occurs in people who were thought to be well, may occur without warning symptoms, and is often the first presentation of an underlying genetic heart disease. Across all ages, estimates differ from 5% to 20% of all deaths, and ethnicity-specific data on SCD incidences worldwide are sparse. Cause of death changes according to age (Figure 1). Exact estimates of the burden of SCD are crucial in order to adjudicate public health spending.
      Recommendation-Specific Supportive Text
      • 1. and 2. Inherited cardiac disorders are the main cause of SCD in the young. Sudden death is SCD in 60–90% depending on age, of which the majority is potentially from inherited cardiac disease.
        • Fellmann F.
        • van El C.G.
        • Charron P.
        • et al.
        European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death.
        ,
        • Winkel B.G.
        • Holst A.G.
        • Theilade J.
        • et al.
        Nationwide study of sudden cardiac death in persons aged 1-35 years.
        ,
        • Basso C.
        • Calabrese F.
        • Corrado D.
        • Thiene G.
        Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings.
        Exact estimates of the burden of SCD are crucial in order to adjudicate public health spending.
        • Bagnall R.D.
        • Weintraub R.G.
        • Ingles J.
        • et al.
        A prospective study of sudden cardiac death among children and young adults.
      • 3.
        Estimates of SCD among different ethnic backgrounds are sparse worldwide.
        • Becker L.B.
        • Han B.H.
        • Meyer P.M.
        • et al.
        Racial differences in the incidence of cardiac arrest and subsequent survival: the CPR Chicago Project.
        ,
        • Zhao D.
        • Post W.S.
        • Blasco-Colmenares E.
        • et al.
        Racial differences in sudden cardiac death.
        ,
        • Griffis H.
        • Wu L.
        • Naim M.Y.
        • et al.
        Characteristics and outcomes of AED use in pediatric cardiac arrest in public settings: the influence of neighborhood characteristics.
        ,
        • Starks M.A.
        • Schmicker R.H.
        • Peterson E.D.
        • et al.
        Association of neighborhood demographics with out-of-hospital cardiac arrest treatment and outcomes: where you live may matter.

      2.2 Epidemiology: Sudden Cardiac Arrest Survivors

      2.2.1 Background

      Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality globally
      • Sasson C.
      • Rogers M.A.
      • Dahl J.
      • Kellermann A.L.
      Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis.
      • Berdowski J.
      • Berg R.A.
      • Tijssen J.G.
      • Koster R.W.
      Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies.
      • Otsuki S.
      • Aiba T.
      • Tahara Y.
      • et al.
      Intra-day change in occurrence of out-of-hospital ventricular fibrillation in Japan: the JCS-ReSS study.
      and is defined as the loss of functional cardiac mechanical activity in association with an absence of systemic circulation, occurring outside of a hospital setting. The exact burden of OHCA remains unknown, since a considerable number of cases are not attended by emergency medical services (EMS) and regional variations are prevalent in both reporting systems and survival.
      • Nichol G.
      • Thomas E.
      • Callaway C.W.
      • et al.
      Regional variation in out-of-hospital cardiac arrest incidence and outcome.
      ,
      • Zive D.
      • Koprowicz K.
      • Schmidt T.
      • et al.
      Variation in out-of-hospital cardiac arrest resuscitation and transport practices in the Resuscitation Outcomes Consortium: ROC Epistry-Cardiac Arrest.
      ,
      • Girotra S.
      • van Diepen S.
      • Nallamothu B.K.
      • et al.
      Regional variation in out-of-hospital cardiac arrest survival in the United States.
      Approximately 275,000 people in Europe have cardiac arrest treated by EMS per year, with only 29,000 (10.5%) surviving hospital discharge.
      • Atwood C.
      • Eisenberg M.S.
      • Herlitz J.
      • Rea T.D.
      Incidence of EMS-treated out-of-hospital cardiac arrest in Europe.
      In England, 28,729 EMS-treated OHCA cases were reported in 2014 (53 cases per 100,000 of the resident population), with only 7.9% surviving to hospital discharge.
      • Hawkes C.
      • Booth S.
      • Ji C.
      • et al.
      Epidemiology and outcomes from out-of-hospital cardiac arrests in England.
      In the United States, reports from 35 communities suggested an incidence of 55 per 100,000 person-years
      • Rea T.D.
      • Eisenberg M.S.
      • Sinibaldi G.
      • White R.D.
      Incidence of EMS-treated out-of-hospital cardiac arrest in the United States.
      or approximately 155,000 individuals having an EMS-treated all-rhythm OHCA per year.
      • Rea T.D.
      • Eisenberg M.S.
      • Sinibaldi G.
      • White R.D.
      Incidence of EMS-treated out-of-hospital cardiac arrest in the United States.
      Globally, the weighted incidence estimates per 100,000 person-years of EMS-treated OHCA are 34.4 in Europe, 53.1 in North America, 59.4 in Asia, and 49.7 in Australia. For reported survival estimates, the percentage survival to discharge was 7.6% in Europe, 6.8% in North America, 3.0% in Asia, and 9.7% in Australia.
      • Berdowski J.
      • Berg R.A.
      • Tijssen J.G.
      • Koster R.W.
      Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies.
      Significant geographical variation in the incidence of OHCA associated with poor outcomes has remained unchanged in the past 3 decades.
      • Nichol G.
      • Thomas E.
      • Callaway C.W.
      • et al.
      Regional variation in out-of-hospital cardiac arrest incidence and outcome.
      ,
      • Sasson C.
      • Rogers M.A.
      • Dahl J.
      • Kellermann A.L.
      Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis.
      ,
      • Berdowski J.
      • Berg R.A.
      • Tijssen J.G.
      • Koster R.W.
      Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies.
      ,
      • Zive D.
      • Koprowicz K.
      • Schmidt T.
      • et al.
      Variation in out-of-hospital cardiac arrest resuscitation and transport practices in the Resuscitation Outcomes Consortium: ROC Epistry-Cardiac Arrest.
      However, implementation of coordinated efforts targeted at improving the local chain of survival in some cities has improved regional survival to 20–40%.
      • Becker L.
      • Gold L.S.
      • Eisenberg M.
      • White L.
      • Hearne T.
      • Rea T.
      Ventricular fibrillation in King County, Washington: a 30-year perspective.
      ,
      • Bunch T.J.
      • White R.D.
      • Gersh B.J.
      • et al.
      Long-term outcomes of out-of-hospital cardiac arrest after successful early defibrillation.
      This survival benefit can be partially attributed to varying definitions of OHCA,
      • Berdowski J.
      • Berg R.A.
      • Tijssen J.G.
      • Koster R.W.
      Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies.
      but it is primarily due to a coordinated effort to optimize the effectiveness of the local chain of survival.
      • Cummins R.O.
      • Ornato J.P.
      • Thies W.H.
      • Pepe P.E.
      Improving survival from sudden cardiac arrest: the "chain of survival" concept. A statement for health professionals from the Advanced Cardiac Life Support Subcommittee and the Emergency Cardiac Care Committee, American Heart Association.
      Identifying and improving weak links in the local chain of survival, paired with targeted approaches to improve the effectiveness, has resulted in positive outcomes achieved in several geographic regions.
      • Becker L.
      • Gold L.S.
      • Eisenberg M.
      • White L.
      • Hearne T.
      • Rea T.
      Ventricular fibrillation in King County, Washington: a 30-year perspective.
      ,
      • Iwami T.
      • Nichol G.
      • Hiraide A.
      • et al.
      Continuous improvements in "chain of survival" increased survival after out-of-hospital cardiac arrests: a large-scale population-based study.
      • Lund-Kordahl I.
      • Olasveengen T.M.
      • Lorem T.
      • Samdal M.
      • Wik L.
      • Sunde K.
      Improving outcome after out-of-hospital cardiac arrest by strengthening weak links of the local Chain of Survival; quality of advanced life support and post-resuscitation care.
      • Wissenberg M.
      • Lippert F.K.
      • Folke F.
      • et al.
      Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest.

      2.2.2 Causes of Out-of-Hospital Cardiac Arrest

      OHCA causes are classified into cardiac and noncardiac causes.
      • Hawkes C.
      • Booth S.
      • Ji C.
      • et al.
      Epidemiology and outcomes from out-of-hospital cardiac arrests in England.
      ,
      • Moriwaki Y.
      • Tahara Y.
      • Kosuge T.
      • Suzuki N.
      Etiology of out-of-hospital cardiac arrest diagnosed via detailed examinations including perimortem computed tomography.
      ,
      • Engdahl J.
      • Holmberg M.
      • Karlson B.W.
      • Luepker R.
      • Herlitz J.
      The epidemiology of out-of-hospital 'sudden' cardiac arrest.
      Approximately 80% of individuals presenting with OHCA reached by EMS, and in whom resuscitation is considered possible, have a cardiac cause.
      • Engdahl J.
      • Holmberg M.
      • Karlson B.W.
      • Luepker R.
      • Herlitz J.
      The epidemiology of out-of-hospital 'sudden' cardiac arrest.
      OHCA can affect seemingly fit and healthy athletes, young adults, or children. The incidence of SCD in athletes can range from 1 in 23,000 to 1 in 200,000 athletes per year, depending on a number of factors including populations studied.
      • D'Silva A.
      • Sharma S.
      Management of young competitive athletes with cardiovascular conditions.
      ,
      • Asatryan B.
      • Vital C.
      • Kellerhals C.
      • et al.
      Sports-related sudden cardiac deaths in the young population of Switzerland.
      In a retrospective analysis of the Rescu Epistry database of consecutive OHCA attended by EMS in a specific area of Ontario, Canada, the incidence of SCD during participation in competitive sports was reported to be 0.76 cases per 100,000 athlete-years.
      • Landry C.H.
      • Allan K.S.
      • Connelly K.A.
      • Cunningham K.
      • Morrison L.J.
      • Dorian P.
      Sudden cardiac arrest during participation in competitive sports.
      The main causes of SCD were stratified by age. In those younger than 35 years, structural heart and primary arrhythmic causes were most common. In those aged between 35 and 45 years, coronary artery disease was the most frequent underlying pathology.
      • Landry C.H.
      • Allan K.S.
      • Connelly K.A.
      • Cunningham K.
      • Morrison L.J.
      • Dorian P.
      Sudden cardiac arrest during participation in competitive sports.
      In a prospective study of children and young adults aged 1–35 years, 490 cases of SCD were identified from centers in Australia and New Zealand.
      • Bagnall R.D.
      • Weintraub R.G.
      • Ingles J.
      • et al.
      A prospective study of sudden cardiac death among children and young adults.
      The cause of death was unexplained in 40% of these cases at autopsy, in whom a structurally normal heart was reported.
      • Bagnall R.D.
      • Weintraub R.G.
      • Ingles J.
      • et al.
      A prospective study of sudden cardiac death among children and young adults.
      In this study, the annual incidence of SCD was calculated to be 1.3 cases per 100,000 people. When stratified according to age group, the highest incidence (3.2 cases per 100,000 people per year) was observed in those aged 31–35 years. Coronary artery disease was the most common cause ascribed. Younger age and SCD occurring at night were independently associated with unexplained SCD, probably due to congenital channelopathies. Less common causes were inherited cardiomyopathies (eg, dilated, hypertrophic, and arrhythmogenic right ventricular), myocarditis, and aortic dissection.
      The Cardiac Arrest Registry to Enhance Survival (CARES), established by the Centers for Disease Control and Prevention (CDC),
      • McNally B.
      • Robb R.
      • Mehta M.
      • et al.
      Out-of-hospital cardiac arrest surveillance: Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005-December 31, 2010.
      evaluated OHCA events of presumed cardiac etiology that involve persons who received resuscitative effort. OHCA is defined in CARES as a cardiac arrest that occurred in the prehospital setting, had a presumed cardiac etiology, and involved a person who received resuscitative efforts, including cardiopulmonary resuscitation (CPR) or defibrillation. The registry includes 40,274 OHCA records, of which 31,689 OHCA events were presumed to be of cardiac etiology (eg, myocardial infarction or arrhythmia) that received resuscitation efforts in the prehospital setting (mean age 64.0 years [SD 18.2]; 61.1% male). The survival rate to hospital admission was 26.3%, and the overall survival rate from cardiac arrest to hospital discharge was 9.6% (Figure 2). Approximately 36.7% of OHCA events were witnessed by a bystander. Only 33.3% of all patients received bystander CPR, and only 3.7% were treated by bystanders with an automated external defibrillator (AED) before the arrival of EMS providers.
      Figure thumbnail gr2
      Figure 2Cumulative overall survival rates, by participating emergency medical services agency—Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005–December 31, 2010. Agencies sorted by total number of out-of-hospital cardiac arrest events in CARES (from low to high; range: 18–5,434).
      • McNally B.
      • Robb R.
      • Mehta M.
      • et al.
      Out-of-hospital cardiac arrest surveillance: Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005-December 31, 2010.
      The group most likely to survive an OHCA is persons who are witnessed to collapse by a bystander and found in a shockable rhythm (ie, arrhythmias leading to ventricular fibrillation or pulseless ventricular tachycardia).
      • McNally B.
      • Robb R.
      • Mehta M.
      • et al.
      Out-of-hospital cardiac arrest surveillance: Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005-December 31, 2010.
      Among this group, survival to discharge was 30.1% (Figure 3). A subgroup analysis, performed among persons who experienced OHCA events unwitnessed by EMS, revealed that whites were significantly more likely to receive CPR than blacks, Hispanics, or members of other racial/ethnic populations (p < 0.001). Overall survival to hospital discharge of patients whose events were not witnessed by EMS personnel was 8.5%. Of these, patients who received bystander CPR had a significantly higher rate of overall survival (11.2%) than those who did not (7.0%) (p < 0.001).
      Figure thumbnail gr3
      Figure 3Cumulative Utstein survival rates (patients alive when arriving to hospital) by participating emergency medical services agency—Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005–December 31, 2010. Agencies sorted by total number of out-of-hospital cardiac arrest events in CARES (from low to high).
      • McNally B.
      • Robb R.
      • Mehta M.
      • et al.
      Out-of-hospital cardiac arrest surveillance: Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005-December 31, 2010.
      †Utstein survival refers to survival to hospital discharge of persons whose cardiac arrest events were witnessed by a bystander and had an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia (range: 0–598).
      Figure 4 shows bystander CPR and lay AED use by percentage of black residents in the area. Directing attention toward improving education, availability of AEDs, and treatment of cardiac arrest in predominantly black neighborhoods may save lives.
      • Starks M.A.
      • Schmicker R.H.
      • Peterson E.D.
      • et al.
      Association of neighborhood demographics with out-of-hospital cardiac arrest treatment and outcomes: where you live may matter.
      Figure thumbnail gr4
      Figure 4Bystander treatments of patients with out-of-hospital cardiac arrest before emergency medical services arrival among neighborhoods by percentage of black residents. Reprinted with permission from the American Medical Association.
      • Starks M.A.
      • Schmicker R.H.
      • Peterson E.D.
      • et al.
      Association of neighborhood demographics with out-of-hospital cardiac arrest treatment and outcomes: where you live may matter.
      AED = automated external defibrillator; CPR = cardiopulmonary resuscitation.
      Bystander AED use in OHCA in pediatric populations is variable and uncommon, with important variations based on neighborhood characteristics leading to marked disparities in survival and outcomes. Griffis et al.
      • Griffis H.
      • Wu L.
      • Naim M.Y.
      • et al.
      Characteristics and outcomes of AED use in pediatric cardiac arrest in public settings: the influence of neighborhood characteristics.
      reported that AED use (likely due to availability) was more common in neighborhoods with a median household income of >$50,000 per year (12.3%; p = 0.016), <10% unemployment (12.1%; p = 0.002), and >80% high school education (11.8%; p = 0.002). Greater survival to hospital discharge and neurologically favorable survival were among arrests with bystander AED use, varying by neighborhood characteristics.

      2.2.3 Public Health Implications

      The majority of persons who experience an OHCA event, irrespective of etiology, do not receive bystander CPR or other timely interventions that are known to improve the likelihood of survival to hospital discharge (eg, defibrillation).
      • Wissenberg M.
      • Lippert F.K.
      • Folke F.
      • et al.
      Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest.
      Because nearly half of cardiac arrest events are witnessed, efforts to increase survival rates should focus on timely and effective delivery of interventions by bystanders and EMS personnel (Figure 5).
      Figure thumbnail gr5
      Figure 5Bystander-witnessed arrest, bystander cardiopulmonary resuscitation (CPR), shockable heart rhythm as first recorded rhythm, and survival on arrival at the hospital, Denmark, 2001–2010. Reprinted with permission from the American Medical Association.
      • Wissenberg M.
      • Lippert F.K.
      • Folke F.
      • et al.
      Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest.
      Tabled 1Recommendations for improving outcomes in SCA survivors
      CORLOERecommendationsReferences
      1B-NR
      • 1.
        Targeted CPR training should be widely implemented with particular emphasis on low-income communities, ethnic minorities, and middle- to low-income countries.
      • Griffis H.
      • Wu L.
      • Naim M.Y.
      • et al.
      Characteristics and outcomes of AED use in pediatric cardiac arrest in public settings: the influence of neighborhood characteristics.
      ,
      • McNally B.
      • Robb R.
      • Mehta M.
      • et al.
      Out-of-hospital cardiac arrest surveillance: Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005-December 31, 2010.
      1B-NR
      • 2.
        The burden of out-of-hospital SCA and varied outcomes in different ethnic populations and socioeconomic backgrounds should be investigated worldwide.
      • Becker L.B.
      • Han B.H.
      • Meyer P.M.
      • et al.
      Racial differences in the incidence of cardiac arrest and subsequent survival: the CPR Chicago Project.
      ,
      • Griffis H.
      • Wu L.
      • Naim M.Y.
      • et al.
      Characteristics and outcomes of AED use in pediatric cardiac arrest in public settings: the influence of neighborhood characteristics.
      ,
      • Starks M.A.
      • Schmicker R.H.
      • Peterson E.D.
      • et al.
      Association of neighborhood demographics with out-of-hospital cardiac arrest treatment and outcomes: where you live may matter.
      1B-NR
      • 3.
        Appropriately maintained AEDs should be readily available at schools, stadiums, public transport stations, casinos, etc, as well as venues where no other access to AEDs is available (eg, trains, ships, planes), with appropriate training of users.
      • Hallstrom A.P.
      • Ornato J.P.
      • Weisfeldt M.
      • et al.
      Public-access defibrillation and survival after out-of-hospital cardiac arrest.
      ,
      • Capucci A.
      • Aschieri D.
      • Piepoli M.F.
      • Bardy G.H.
      • Iconomu E.
      • Arvedi M.
      Tripling survival from sudden cardiac arrest via early defibrillation without traditional education in cardiopulmonary resuscitation.
      Figure thumbnail gr6
      Figure 6Examples of complimentary bystander cardiopulmonary resuscitation (CPR) programs. Reprinted with permission from Elsevier.
      • Myat A.
      • Song K.J.
      • Rea T.
      Out-of-hospital cardiac arrest: current concepts.
      Synopsis
      OHCA remains a significant cause of mortality globally. Despite implementation of cardiac arrest protocols including CPR training and AEDs, only 33% of witnessed OHCA cases receive bystander CPR and less than 4% are defibrillated onsite. OHCA hospital discharge survival remains dismal at around 10% and has remained stagnant for the past 3 decades. Significant geographic variation in OHCA incidence and the role of social disparities merit further research. Public health campaigns promoting CPR training in at-risk communities and greater availability of AEDs are needed.
      Recommendation-Specific Supportive Text
      • 1.
        Coordinated efforts targeted at improving the local chain of survival have improved regional survival.
        • Becker L.
        • Gold L.S.
        • Eisenberg M.
        • White L.
        • Hearne T.
        • Rea T.
        Ventricular fibrillation in King County, Washington: a 30-year perspective.
        ,
        • Bunch T.J.
        • White R.D.
        • Gersh B.J.
        • et al.
        Long-term outcomes of out-of-hospital cardiac arrest after successful early defibrillation.
        Targeted approaches to improve the effectiveness of CPR have resulted in positive outcomes.
        • Iwami T.
        • Nichol G.
        • Hiraide A.
        • et al.
        Continuous improvements in "chain of survival" increased survival after out-of-hospital cardiac arrests: a large-scale population-based study.
        • Lund-Kordahl I.
        • Olasveengen T.M.
        • Lorem T.
        • Samdal M.
        • Wik L.
        • Sunde K.
        Improving outcome after out-of-hospital cardiac arrest by strengthening weak links of the local Chain of Survival; quality of advanced life support and post-resuscitation care.
        • Wissenberg M.
        • Lippert F.K.
        • Folke F.
        • et al.
        Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest.
        The group most likely to survive an OHCA is persons who are witnessed to collapse by a bystander and found in a shockable rhythm, so widespread CPR training is recommended. Subgroup analysis has revealed that whites were significantly more likely to receive CPR than other racial/ethnic populations.
        • McNally B.
        • Robb R.
        • Mehta M.
        • et al.
        Out-of-hospital cardiac arrest surveillance: Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005-December 31, 2010.
        AED use was more common in neighborhoods with high median household income, <10% unemployment, and >80% high school education.
        • Griffis H.
        • Wu L.
        • Naim M.Y.
        • et al.
        Characteristics and outcomes of AED use in pediatric cardiac arrest in public settings: the influence of neighborhood characteristics.
        Therefore, maximum benefit will be gained from targeting CPR training to groups of high socioeconomic need and ethnic minorities.
      • 2.
        The burden of OHCA and the response of bystanders appears to vary according to ethnicity and socioeconomic status.
        • Becker L.B.
        • Han B.H.
        • Meyer P.M.
        • et al.
        Racial differences in the incidence of cardiac arrest and subsequent survival: the CPR Chicago Project.
        ,
        • Griffis H.
        • Wu L.
        • Naim M.Y.
        • et al.
        Characteristics and outcomes of AED use in pediatric cardiac arrest in public settings: the influence of neighborhood characteristics.
        ,
        • Starks M.A.
        • Schmicker R.H.
        • Peterson E.D.
        • et al.
        Association of neighborhood demographics with out-of-hospital cardiac arrest treatment and outcomes: where you live may matter.
        ,
        • McNally B.
        • Robb R.
        • Mehta M.
        • et al.
        Out-of-hospital cardiac arrest surveillance: Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005-December 31, 2010.
        Further investigation of these findings may result in targeted approaches to maximize outcome from investment when aimed at these communities.
      • 3.
        Availability of AEDs has been shown to improve survival.
        • Hallstrom A.P.
        • Ornato J.P.
        • Weisfeldt M.
        • et al.
        Public-access defibrillation and survival after out-of-hospital cardiac arrest.
        • Capucci A.
        • Aschieri D.
        • Piepoli M.F.
        • Bardy G.H.
        • Iconomu E.
        • Arvedi M.
        Tripling survival from sudden cardiac arrest via early defibrillation without traditional education in cardiopulmonary resuscitation.
        • Blom M.T.
        • Beesems S.G.
        • Homma P.C.
        • et al.
        Improved survival after out-of-hospital cardiac arrest and use of automated external defibrillators.
        Therefore, as the majority of cardiac arrests are witnessed, AEDs at schools, stadiums, stations, etc, may be expected to increase survival. Venues where delivery of AEDs by emergency services is unlikely (eg, trains, ships, planes) are of particular importance. Appropriately maintained equipment and appropriate training of potential AED users are an essential component of this strategy.

      Section 3 Multidisciplinary Team

      3.1 Introduction

      The investigation of SCD and resuscitated SCA requires input from a variety of different disciplines. The coordination and the communication between them mandate the formation of a multidisciplinary team. Numerous consensus statements agree on the importance of a dedicated combined cardiac genetic service in this setting.
      • Fellmann F.
      • van El C.G.
      • Charron P.
      • et al.
      European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death.
      ,
      • Ackerman M.J.
      • Priori S.G.
      • Willems S.
      • et al.
      HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies.
      ,
      • Skinner J.R.
      • Duflou J.A.
      • Semsarian C.
      Reducing sudden death in young people in Australia and New Zealand: the TRAGADY initiative.
      • Ahmad F.
      • McNally E.M.
      • Ackerman M.J.
      • et al.
      Establishment of specialized clinical cardiovascular genetics programs: recognizing the need and meeting standards: a scientific statement from the American Heart Association.
      • Basso C.
      • Aguilera B.
      • Banner J.
      • et al.
      Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology.

      3.2 Key Features of an Effective Multidisciplinary Team

      Certain key features can be identified in well-functioning multidisciplinary teams across specialties. Nancarrow et al.
      • Nancarrow S.A.
      • Booth A.
      • Ariss S.
      • Smith T.
      • Enderby P.
      • Roots A.
      Ten principles of good interdisciplinary team work.
      propose 10 key attributes including positive leadership and management, communication strategies and structures, appropriate resources, appropriate skill mix, and a supportive team climate with a focus on education of each other. There should be open communication and shared decision-making.
      The detection of inherited heart conditions by pathologists and by hospital clinicians requires heightened awareness of their existence and a simple referral pathway to a multidisciplinary service with cardiac genetic expertise. Clinical experience shows that the appointment of a coordinator, as well as an enthusiastic team leader, is essential to facilitate this process, and regular meetings increase relevance and improve attendance
      • Earle N.J.
      • Crawford J.
      • Hayes I.
      • et al.
      Development of a cardiac inherited disease service and clinical registry: a 15-year perspective.
      (Figures 7 and 8).
      Figure thumbnail gr7
      Figure 7Referral flow for cardiac genetic investigation of sudden cardiac death (SCD) or resuscitated sudden cardiac arrest (SCA). MDT = multidisciplinary team.
      Figure thumbnail gr8
      Figure 8Participants in a cardiac genetic service. “Pathologists” includes forensic pathologists. Modified with permission from Elsevier.
      • Earle N.J.
      • Crawford J.
      • Hayes I.
      • et al.
      Development of a cardiac inherited disease service and clinical registry: a 15-year perspective.

      3.3 Defining Which Disciplines Should Be Represented

      The investigation of SUD is led by (forensic) pathology and the investigation of resuscitated SCA by pediatric or adult cardiology, with cardiac heart rhythm specialists and genetic cardiologists often being central. Clinical and molecular genetic specialists and genetic counselors are needed because of the significant role of molecular genetics in achieving a diagnosis and cascade screening, the consideration of multisystem genetic syndromes, and the high prevalence of genetic variants of uncertain significance.
      • Lahrouchi N.
      • Raju H.
      • Lodder E.M.
      • et al.
      Utility of post-mortem genetic testing in cases of sudden arrhythmic death syndrome.
      ,
      • Marcondes L.
      • Crawford J.
      • Earle N.
      • et al.
      Long QT molecular autopsy in sudden unexplained death in the young (1-40 years old): lessons learnt from an eight year experience in New Zealand.
      The high levels of psychological morbidity among SCA survivors and family members of both SCA survivors and decedents mandates access to psychology expertise,
      • Yeates L.
      • Hunt L.
      • Saleh M.
      • Semsarian C.
      • Ingles J.
      Poor psychological wellbeing particularly in mothers following sudden cardiac death in the young.
      • van der Werf C.
      • Onderwater A.T.
      • van Langen I.M.
      • Smets E.M.
      Experiences, considerations and emotions relating to cardiogenetic evaluation in relatives of young sudden cardiac death victims.
      • Caleshu C.
      • Kasparian N.A.
      • Edwards K.S.
      • et al.
      Interdisciplinary psychosocial care for families with inherited cardiovascular diseases.
      and input into the multidisciplinary team helps keep this in focus.
      • Rhodes A.
      • Rosman L.
      • Cahill J.
      • et al.
      Minding the genes: a multidisciplinary approach towards genetic assessment of cardiovascular disease.
      The presence of a specialist cardiac genetic nurse in the cardiology inpatient setting increases detection of inherited cardiac conditions following SCA.
      • Waddell-Smith K.
      • Donoghue T.
      • Graham M.
      • et al.
      The inpatient cardiology visit: missing the opportunity to detect inherited heart conditions.
      Other clinical specialists can be helpful and be drafted in for certain cases—neurologists, pediatricians, metabolic specialists, and intensivists, for example.

      3.4 Coordination Across Disciplines and Other Boundaries

      The fact that the many disciplines may not be co-located highlights the importance of a coordinator to a multidisciplinary service. Co-location is not critical for effective collaboration, and non-co-location should not be an excuse for failed collaboration. A regional or institutional coordinator could be a nurse specialist, genetic counselor, or other allied professional and is vital to facilitate team meetings and communication between specialists and between centers, with primary care and across regions or between states and countries where necessary to facilitate family screening
      • Earle N.J.
      • Crawford J.
      • Hayes I.
      • et al.
      Development of a cardiac inherited disease service and clinical registry: a 15-year perspective.
      ,
      • Waddell-Smith K.E.
      • Donoghue T.
      • Oates S.
      • et al.
      Inpatient detection of cardiac-inherited disease: the impact of improving family history taking.
      (Figure 7).

      3.5 Links to Other Services

      Links to other services as proposed in a recent scientific statement
      • Ahmad F.
      • McNally E.M.
      • Ackerman M.J.
      • et al.
      Establishment of specialized clinical cardiovascular genetics programs: recognizing the need and meeting standards: a scientific statement from the American Heart Association.
      and practiced by some centers already
      • Earle N.J.
      • Crawford J.
      • Hayes I.
      • et al.
      Development of a cardiac inherited disease service and clinical registry: a 15-year perspective.
      include connections to molecular genetic expertise, researchers, primary health providers, between regions, and to a cardiac genetic clinical registry to facilitate family screening and follow-up across traditional boundaries (Figure 8).
      Clinical and genetic registries are generally voluntary and consent-based and have a research element. We do not consider that they are compulsory. However, in this setting they do have particular relevance because many cases remain unresolved after the initial investigation and families may find comfort in knowing that efforts to find a diagnosis continue. The multidisciplinary team also provides a mechanism to revisit family members if new findings appear in the wider family or if the pathogenicity of a genetic variant is redefined.
      Tabled 1Recommendations for the role of a multidisciplinary team for investigation of SUD and SCA
      CORLOERecommendationsReferences
      1B-NR
      • 1.
        The investigation of SUD and SCD due to a potentially heritable condition should be overseen by a multidisciplinary team with, as a minimum, appropriate expertise in pediatric and/or adult cardiology, genetics, genetic counseling, and pathology.
      • Earle N.
      • Crawford J.
      • Gibson K.
      • et al.
      Detection of sudden death syndromes in New Zealand.
      • Ingles J.
      • Lind J.M.
      • Phongsavan P.
      • Semsarian C.
      Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy.
      • Tan H.L.
      • Hofman N.
      • van Langen I.M.
      • van der Wal A.C.
      • Wilde A.A.
      Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives.
      • Behr E.
      • Wood D.A.
      • Wright M.
      • et al.
      Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome.
      • Kumar S.
      • Peters S.
      • Thompson T.
      • et al.
      Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes.
      1B-NR
      • 2.
        The investigation of a sudden cardiac arrest survivor where a heritable condition is possible should be overseen by a multidisciplinary team with, as a minimum, appropriate expertise in pediatric and/or adult cardiology, genetics, and genetic counseling.
      • Ingles J.
      • Lind J.M.
      • Phongsavan P.
      • Semsarian C.
      Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy.
      ,
      • Kumar S.
      • Peters S.
      • Thompson T.
      • et al.
      Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes.
      • Giudicessi J.R.
      • Lieve K.V.V.
      • Rohatgi R.K.
      • et al.
      Assessment and validation of a phenotype-enhanced variant classification framework to promote or demote RYR2 missense variants of uncertain significance.
      • Mellor G.
      • Laksman Z.W.M.
      • Tadros R.
      • et al.
      Genetic testing in the evaluation of unexplained cardiac arrest.
      • van der Werf C.
      • Hofman N.
      • Tan H.L.
      • et al.
      Diagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: the experience of a tertiary referral center in the Netherlands.
      Synopsis
      The cardiac and genetic investigation of SUD and resuscitated SCA should be overseen by a multidisciplinary team with appropriate expertise in this area. Recommendations include adequate resourcing, a dedicated coordinator, strong leadership, and a mutually supportive team that meets regularly.
      Recommendation-Specific Supportive Text
      • 1.
        For regions where coordinated cardiac genetic services exist that include the investigation of SUD, detection of inherited heart conditions is higher than in regions where they are not.
        • Earle N.
        • Crawford J.
        • Gibson K.
        • et al.
        Detection of sudden death syndromes in New Zealand.
        Families prefer specialized clinics that combine co-located cardiac and genetic expertise and genetic counseling.
        • Ingles J.
        • Lind J.M.
        • Phongsavan P.
        • Semsarian C.
        Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy.
        Many such dedicated clinics internationally have led to the detection of inherited heart conditions following SCD and resuscitated SCA.
        • Tan H.L.
        • Hofman N.
        • van Langen I.M.
        • van der Wal A.C.
        • Wilde A.A.
        Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives.
        • Behr E.
        • Wood D.A.
        • Wright M.
        • et al.
        Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome.
        • Kumar S.
        • Peters S.
        • Thompson T.
        • et al.
        Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes.
        It is therefore logical that multidisciplinary teams should have links to such clinics. Continued productive dialogue among pathology, coronial, police, and cardiac genetic services is recommended to improve the quality and relevance of forensic pathologists’ reports.
        • Wilms H.R.
        • Midgley D.J.
        • Morrow P.
        • Stables S.
        • Crawford J.
        • Skinner J.R.
        Evaluation of autopsy and police reports in the investigation of sudden unexplained death in the young.
      • 2.
        Genetic testing in this context leads to a significant proportion of both pathogenic and unclassified variants, and precise evaluation of clinical phenotype is imperative for the correct assignation of such variants, so that a service that combines specialist cardiology and genetic expertise is essential.
        • Giudicessi J.R.
        • Lieve K.V.V.
        • Rohatgi R.K.
        • et al.
        Assessment and validation of a phenotype-enhanced variant classification framework to promote or demote RYR2 missense variants of uncertain significance.
        ,
        • Mellor G.
        • Laksman Z.W.M.
        • Tadros R.
        • et al.
        Genetic testing in the evaluation of unexplained cardiac arrest.
        Specialized clinics that combine co-located cardiac and genetic expertise and genetic counseling are preferred,
        • Ingles J.
        • Lind J.M.
        • Phongsavan P.
        • Semsarian C.
        Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy.
        and such combined clinics have a high detection of inherited cardiac conditions following resuscitated SCA.
        • Kumar S.
        • Peters S.
        • Thompson T.
        • et al.
        Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes.
        ,
        • van der Werf C.
        • Hofman N.
        • Tan H.L.
        • et al.
        Diagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: the experience of a tertiary referral center in the Netherlands.

      Section 4 Counseling Families, the Bereaved and the Nearly Bereaved

      Genetic counseling is a process that aims to assist patients and their families to understand and adapt to the medical, psychosocial, and familial impact of inherited diseases.
      • Biesecker B.
      Goals of genetic counselling.
      ,
      • Resta R.
      • Biesecker B.B.
      • Bennett R.L.
      • et al.
      A new definition of Genetic Counseling: National Society of Genetic Counselors' Task Force report.
      Genetic counseling goes beyond the discussion of genetic testing and is important for all patients with a genetic condition, at all stages of management.
      • Charron P.
      • Arad M.
      • Arbustini E.
      • et al.
      Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.
      Although genetic counseling may be performed by any number of health professionals, genetic counselors are specifically trained in this role and have grown to a large allied health workforce worldwide.
      • Abacan M.
      • Alsubaie L.
      • Barlow-Stewart K.
      • et al.
      The global state of the genetic counseling profession.
      ,
      • Laurino M.Y.
      • Leppig K.A.
      • Abad P.J.
      • et al.
      A report on ten Asia Pacific countries on current status and future directions of the genetic counseling profession: the establishment of the Professional Society of Genetic Counselors in Asia.
      In some institutions, this role may be performed by a clinical/medical geneticist, genetic nurse, or other appropriately trained specialist.
      In the setting of SCD or resuscitated SCA where a genetic cause is suspected, the inclusion of genetic counselors in the multidisciplinary team is widely advocated. The role of the cardiac genetic counselor includes taking a detailed family history, investigating and confirming details such as postmortem reports, providing education and awareness, assisting in coordinating family clinical screening, and providing psychosocial support.
      • Caleshu C.
      • Kasparian N.A.
      • Edwards K.S.
      • et al.
      Interdisciplinary psychosocial care for families with inherited cardiovascular diseases.
      ,
      • Ingles J.
      • Yeates L.
      • Semsarian C.
      The emerging role of the cardiac genetic counselor.
      • Hershberger R.E.
      • Givertz M.
      • Ho C.Y.
      • et al.
      Genetic evaluation of cardiomyopathy: a Heart Failure Society of America Practice Guideline.
      • Skrzynia C.
      • Demo E.M.
      • Baxter S.M.
      Genetic counseling and testing for hypertrophic cardiomyopathy: an adult perspective.
      • Ingles J.
      Psychological issues in managing families with inherited cardiovascular diseases.
      Throughout the process of genetic testing, genetic counselors provide important pre- and post-test genetic counseling, assist with interpretation of the results, help communicate this information to relatives, and assist with cascade genetic testing
      • Rhodes A.
      • Rosman L.
      • Cahill J.
      • et al.
      Minding the genes: a multidisciplinary approach towards genetic assessment of cardiovascular disease.
      ,
      • Hershberger R.E.
      • Givertz M.
      • Ho C.Y.
      • et al.
      Genetic evaluation of cardiomyopathy: a Heart Failure Society of America Practice Guideline.
      ,
      • Aatre R.D.
      • Day S.M.
      Psychological issues in genetic testing for inherited cardiovascular diseases.
      ,
      • Sturm A.C.
      Genetic testing in the contemporary diagnosis of cardiomyopathy.
      (Table 4).
      Table 4Key goals of genetic counseling following sudden cardiac death/resuscitated sudden cardiac arrest
      GoalDescription
      Genetic counseling about inheritance risksProvide information tailored specifically to the family about their inheritance risks.
      Provide education and awarenessEducate about inheritance risks, the need for clinical surveillance, and options for genetic testing to allow the family to make subsequent important medical decisions. Conveying information is not straightforward, given varying health literacy and competing health concerns; however, genetic counseling can support effective communication.
      • Burns C.
      • James C.
      • Ingles J.
      Communication of genetic information to families with inherited rhythm disorders.
      Genetic counseling can also include connection of families with advocacy organizations and relevant research studies.
      Pre- and post-test genetic counselingExplain the process and discuss the options of genetic testing, all possible outcomes of testing, implications for patients and/or their family members, and worries and fears about testing; ensure consideration of all possible results and implications.
      • Liu G.
      • MacLeod H.
      • Webster G.
      • McNally E.M.
      • O'Neill S.M.
      • Dellefave-Castillo L.
      Genetic counselors' approach to postmortem genetic testing after sudden death: an exploratory study.
      Care should be taken in conveying test results of uncertain significance,
      • Bates K.
      • Sweeting J.
      • Yeates L.
      • McDonald K.
      • Semsarian C.
      • Ingles J.
      Psychological adaptation to molecular autopsy findings following sudden cardiac death in the young.
      ,
      • Burns C.
      • Yeates L.
      • Spinks C.
      • Semsarian C.
      • Ingles J.
      Attitudes, knowledge and consequences of uncertain genetic findings in hypertrophic cardiomyopathy.
      specifically ensuring adequate understanding and confidence to communicate key risk information to family members.
      Pre- and post-test genetic counseling for cascade testing of asymptomatic relativesThere are ethical, legal, and social implications when considering cascade genetic testing of asymptomatic at-risk relatives. Careful pre-test genetic counseling should explore the individual’s feelings toward their risk, how they might feel if they are gene positive or gene negative, and implications for their own health and clinical management based on their genetic result. Discussion about the potential for reclassification of the genetic result is also important.
      • Wong E.K.
      • Bartels K.
      • Hathaway J.
      • et al.
      Perceptions of genetic variant reclassification in patients with inherited cardiac disease.
      ,
      • Ingles J.
      • Semsarian C.
      Conveying a probabilistic genetic test result to families with an inherited heart disease.
      Provide input regarding classification of genetic variantsKnowledge of variant and gene curation processes will enable review of any genetic test findings at all stages of family management.
      • Reuter C.
      • Grove M.E.
      • Orland K.
      • Spoonamore K.
      • Caleshu C.
      Clinical cardiovascular genetic counselors take a leading role in team-based variant classification.
      Clinicians involved in family management (including genetic counselors) are more likely to provide conservative variant classifications compared to clinical laboratories,
      • Bland A.
      • Harrington E.A.
      • Dunn K.
      • et al.
      Clinically impactful differences in variant interpretation between clinicians and testing laboratories: a single-center experience.
      and processes to guarantee regular review of variants will ensure appropriate reclassifications are made.
      • Furqan A.
      • Arscott P.
      • Girolami F.
      • et al.
      Care in specialized centers and data sharing increase agreement in hypertrophic cardiomyopathy genetic test interpretation.
      ,
      • Das K.J.
      • Ingles J.
      • Bagnall R.D.
      • Semsarian C.
      Determining pathogenicity of genetic variants in hypertrophic cardiomyopathy: importance of periodic reassessment.
      Obtain detailed three-generation family history and confirm detailsRecord family history information in a pedigree and interpret the information and the risk posed to family members. Taking a detailed family history can allow development of rapport, elucidate family relationships and social circumstances, and inform clinical care.
      • Dunn K.E.
      • Caleshu C.
      • Cirino A.L.
      • Ho C.Y.
      • Ashley E.A.
      A clinical approach to inherited hypertrophy: the use of family history in diagnosis, risk assessment, and management.
      Assist with coordination of family clinical screeningEnsure adequate understanding of the clinical screening recommendations for family members and provide assistance with communicating this to relatives as needed. Provide support in organizing cardiology appointments with appropriate tests.
      • Ingles J.
      • Yeates L.
      • Semsarian C.
      The emerging role of the cardiac genetic counselor.
      Provide psychosocial support and identify when referral to clinical psychologist is requiredAlthough genetic counseling is unlikely to resolve any significant psychopathologies, the process of providing information and a big picture perspective allowing a patient to normalize their experience and emotional response can have a positive impact, including patient empowerment.
      • Edwards A.
      • Gray J.
      • Clarke A.
      • et al.
      Interventions to improve risk communication in clinical genetics: systematic review.
      ,
      • Michie S.
      • Marteau T.M.
      • Bobrow M.
      Genetic counselling: the psychological impact of meeting patients' expectations.
      ,
      • Ison H.E.
      • Ware S.M.
      • Schwantes-An T.H.
      • Freeze S.
      • Elmore L.
      • Spoonamore K.G.
      The impact of cardiovascular genetic counseling on patient empowerment.
      Where there are significant emotional difficulties (see Section 5), the process of effectively conveying genetic information can be challenging.
      • Burns C.
      • McGaughran J.
      • Davis A.
      • Semsarian C.
      • Ingles J.
      Factors influencing uptake of familial long QT syndrome genetic testing.
      For families who have experienced a young SCD where a genetic cause is suspected, learning the potential inheritance risk to family members and need for clinical screening can add an additional stressor at a time of intense grief. Furthermore, with the increasing availability of postmortem genetic testing (see Sections 6.4 and 6.5), the need for complex genetic discussions with families is more commonplace.
      • Ingles J.
      • James C.
      Psychosocial care and cardiac genetic counseling following sudden cardiac death in the young.
      Genetic counseling prior to and after genetic testing is important, particularly where genetic test results are not straightforward such as identification of variants of uncertain significance or in the event of a variant reclassification.
      • Wong E.K.
      • Bartels K.
      • Hathaway J.
      • et al.
      Perceptions of genetic variant reclassification in patients with inherited cardiac disease.
      ,
      • Bates K.
      • Sweeting J.
      • Yeates L.
      • McDonald K.
      • Semsarian C.
      • Ingles J.
      Psychological adaptation to molecular autopsy findings following sudden cardiac death in the young.
      There is wide acknowledgment that genetic counseling as a process should go beyond just provision of information.
      • Meiser B.
      • Irle J.
      • Lobb E.
      • Barlow-Stewart K.
      Assessment of the content and process of genetic counseling: a critical review of empirical studies.
      ,
      • Edwards A.
      • Gray J.
      • Clarke A.
      • et al.
      Interventions to improve risk communication in clinical genetics: systematic review.
      The psychosocial aspects of genetic counseling include psychological support, empathic listening, crisis intervention skills, knowledge of family dynamics, coping models, processes of grief, and adjustment to disease diagnoses, all of which align with the core competencies of genetic counseling accreditation.
      • Austin J.
      • Semaka A.
      • Hadjipavlou G.
      Conceptualizing genetic counseling as psychotherapy in the era of genomic medicine.
      ,
      Accreditation Council for Genetic Counseling
      Practice based competencies for genetic counselors.
      Attending to the psychosocial needs, in addition to provision of education and information, has been demonstrated to positively impact patient outcomes, largely based around knowledge and recall, but healthy adjustment, empowerment, behavioral change, and satisfaction with decision-making also reduce anxiety and worry.
      • Edwards A.
      • Gray J.
      • Clarke A.
      • et al.
      Interventions to improve risk communication in clinical genetics: systematic review.
      ,
      • Austin J.
      • Semaka A.
      • Hadjipavlou G.
      Conceptualizing genetic counseling as psychotherapy in the era of genomic medicine.
      ,
      • Michie S.
      • Marteau T.M.
      • Bobrow M.
      Genetic counselling: the psychological impact of meeting patients' expectations.
      ,
      • Ison H.E.
      • Ware S.M.
      • Schwantes-An T.H.
      • Freeze S.
      • Elmore L.
      • Spoonamore K.G.
      The impact of cardiovascular genetic counseling on patient empowerment.
      Tabled 1Recommendations for counseling families affected by SUD and SCA
      CORLOERecommendationsReferences
      1B-NR
      • 1.
        Genetic counseling is strongly recommended for all families where there has been an SUD or resuscitated SCA and a heritable cause is suspected, and should include antemortem and postmortem data collection and evaluation, so that risks, benefits, results, and the clinical significance of genetic testing can be discussed.
      • Tan H.L.
      • Hofman N.
      • van Langen I.M.
      • van der Wal A.C.
      • Wilde A.A.
      Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives.
      • Behr E.
      • Wood D.A.
      • Wright M.
      • et al.
      Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome.
      • Kumar S.
      • Peters S.
      • Thompson T.
      • et al.
      Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes.
      ,
      • Mellor G.
      • Laksman Z.W.M.
      • Tadros R.
      • et al.
      Genetic testing in the evaluation of unexplained cardiac arrest.
      ,
      • van der Werf C.
      • Hofman N.
      • Tan H.L.
      • et al.
      Diagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: the experience of a tertiary referral center in the Netherlands.
      ,
      • Edwards A.
      • Gray J.
      • Clarke A.
      • et al.
      Interventions to improve risk communication in clinical genetics: systematic review.
      ,
      • Michie S.
      • Marteau T.M.
      • Bobrow M.
      Genetic counselling: the psychological impact of meeting patients' expectations.
      ,
      • Ison H.E.
      • Ware S.M.
      • Schwantes-An T.H.
      • Freeze S.
      • Elmore L.
      • Spoonamore K.G.
      The impact of cardiovascular genetic counseling on patient empowerment.
      ,
      • Liu G.
      • MacLeod H.
      • Webster G.
      • McNally E.M.
      • O'Neill S.M.
      • Dellefave-Castillo L.
      Genetic counselors' approach to postmortem genetic testing after sudden death: an exploratory study.
      1C-EO
      • 2.
        It is recommended that genetic testing in families where an SUD or resuscitated SCA due to a heritable cause is suspected is performed only with appropriate genetic counseling.
      Synopsis
      Genetic counseling of patients and their families with genetic conditions is recommended, including those with SCD or resuscitated SCA where a genetic cause is suspected. Key aspects of the process include discussion of inheritance risks, education and awareness, pre- and post-test genetic counseling, interpretation of genetic results, taking a family history, coordination of clinical screening, and psychosocial support. Genetic counseling is focused on both information provision and psychosocial support and together has been shown to improve knowledge and recall; promote healthy adjustment, empowerment, and behavioral change; increase satisfaction with decision-making; and reduce anxiety and worry. While genetic counseling is a process often performed by a variety of health professionals, ideally a specifically trained genetic counselor or genetic nurse with appropriate skills in information provision and psychosocial support would perform this role.
      Recommendation-Specific Supportive Text
      • 1.
        Genetic counseling includes both information provision and psychosocial support. It is ideally performed by health professionals with specific training and experience; this includes genetic counselors, genetic nurses, or other qualified health professionals.
        • Tan H.L.
        • Hofman N.
        • van Langen I.M.
        • van der Wal A.C.
        • Wilde A.A.
        Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives.
        • Behr E.
        • Wood D.A.
        • Wright M.
        • et al.
        Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome.
        • Kumar S.
        • Peters S.
        • Thompson T.
        • et al.
        Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes.
        ,
        • Mellor G.
        • Laksman Z.W.M.
        • Tadros R.
        • et al.
        Genetic testing in the evaluation of unexplained cardiac arrest.
        ,
        • van der Werf C.
        • Hofman N.
        • Tan H.L.
        • et al.
        Diagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: the experience of a tertiary referral center in the Netherlands.
        ,
        • Edwards A.
        • Gray J.
        • Clarke A.
        • et al.
        Interventions to improve risk communication in clinical genetics: systematic review.
        ,
        • Michie S.
        • Marteau T.M.
        • Bobrow M.
        Genetic counselling: the psychological impact of meeting patients' expectations.
        ,
        • Ison H.E.
        • Ware S.M.
        • Schwantes-An T.H.
        • Freeze S.
        • Elmore L.
        • Spoonamore K.G.
        The impact of cardiovascular genetic counseling on patient empowerment.
        ,
        • Liu G.
        • MacLeod H.
        • Webster G.
        • McNally E.M.
        • O'Neill S.M.
        • Dellefave-Castillo L.
        Genetic counselors' approach to postmortem genetic testing after sudden death: an exploratory study.
      • 2.
        In the context of genetic testing, pre- and post-test genetic counseling must be performed.
        • Rhodes A.
        • Rosman L.
        • Cahill J.
        • et al.
        Minding the genes: a multidisciplinary approach towards genetic assessment of cardiovascular disease.
        ,
        • Ingles J.
        Psychological issues in managing families with inherited cardiovascular diseases.
        ,
        • Aatre R.D.
        • Day S.M.
        Psychological issues in genetic testing for inherited cardiovascular diseases.
        ,
        • Ingles J.
        • James C.
        Psychosocial care and cardiac genetic counseling following sudden cardiac death in the young.
        In cases where there is uncertainty in the findings, such as a variant of uncertain significance or a variant reclassification, this is of particular importance.
        • Wong E.K.
        • Bartels K.
        • Hathaway J.
        • et al.
        Perceptions of genetic variant reclassification in patients with inherited cardiac disease.
        ,
        • Bates K.
        • Sweeting J.
        • Yeates L.
        • McDonald K.
        • Semsarian C.
        • Ingles J.
        Psychological adaptation to molecular autopsy findings following sudden cardiac death in the young.

      Section 5 Psychological Care

      SCD where a genetic cause is suspected has a profound psychological impact on the surviving members of the family. Grief is a normal emotional response to the loss of a loved one. Individuals will grieve differently, and while there is no single trajectory, many will experience disbelief, yearning, anger, sadness, and acceptance.
      • Shear M.K.
      Getting straight about grief.
      After a death, an individual will not return to normal, but rather create a revised meaningful life without the deceased. In a small proportion of bereaved individuals, the initial grief response does not resolve and may result in prolonged grief, or persistent complex bereavement disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).
      • Simon N.M.
      • Shear K.M.
      • Thompson E.H.
      • et al.
      The prevalence and correlates of psychiatric comorbidity in individuals with complicated grief.
      ,
      American Psychiatric Association
      Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
      This occurs in approximately 7% of the general bereaved population,
      • Simon N.M.
      Treating complicated grief.
      and in 21% of first-degree relatives following SCD in the young.
      • Ingles J.
      • Spinks C.
      • Yeates L.
      • McGeechan K.
      • Kasparian N.
      • Semsarian C.
      Posttraumatic stress and prolonged grief after the sudden cardiac death of a young relative.
      Posttraumatic stress symptoms can also be experienced by family members. Posttraumatic stress occurs in response to a specific trigger, typically one that threatens one’s own or a loved one’s well-being. It is characterized by avoidance with hyperarousal and intrusive thoughts, including persistent and extreme fear and panic similar to that experienced by family members at the time of the event.
      • Shalev A.
      • Liberzon I.
      • Marmar C.
      Post-traumatic stress disorder.
      Posttraumatic stress has been shown in 44% of first-degree relatives following a young SCD.
      • Ingles J.
      • Spinks C.
      • Yeates L.
      • McGeechan K.
      • Kasparian N.
      • Semsarian C.
      Posttraumatic stress and prolonged grief after the sudden cardiac death of a young relative.
      Individuals with prolonged grief and/or posttraumatic stress symptoms can benefit from intervention with a clinical psychologist or other appropriately trained clinicians, and there is extensive evidence to support the efficacy of psychological treatments for these conditions in other settings.
      • Simon N.M.
      Treating complicated grief.
      Further, there is greater risk of other psychiatric comorbidities,
      • Simon N.M.
      • Shear K.M.
      • Thompson E.H.
      • et al.
      The prevalence and correlates of psychiatric comorbidity in individuals with complicated grief.
      suicide,
      • Latham A.E.
      • Prigerson H.G.
      Suicidality and bereavement: complicated grief as psychiatric disorder presenting greatest risk for suicidality.
      and development of chronic medical conditions.
      • Prigerson H.G.
      • Bierhals A.J.
      • Kasl S.V.
      • et al.
      Traumatic grief as a risk factor for mental and physical morbidity.
      Factors associated with poor psychological outcomes have been investigated. One study showed that mothers of the deceased were more likely to report anxiety and depression symptoms.
      • Yeates L.
      • Hunt L.
      • Saleh M.
      • Semsarian C.
      • Ingles J.
      Poor psychological wellbeing particularly in mothers following sudden cardiac death in the young.
      In total, 53% of the mothers surveyed reported probable anxiety disorder on average 4 years after the death. In a larger study, after adjusting for factors including relationship to the decedent, those family members who witnessed the death or discovered the decedent’s body had a 3-fold risk of posttraumatic stress symptoms (OR 3.3, 95% CI 1.2–8.7, p = 0.02) and a 4-fold risk of prolonged grief (OR 4.0, 95% CI 1.3–12.5, p = 0.02).
      • Ingles J.
      • Spinks C.
      • Yeates L.
      • McGeechan K.
      • Kasparian N.
      • Semsarian C.
      Posttraumatic stress and prolonged grief after the sudden cardiac death of a young relative.
      Given that half report symptoms indicating psychological difficulties, all first-degree relatives should be offered psychological evaluation and treatment. Although the evidence for psychological support is derived from studies investigating SCD where a genetic cause is suspected, it may logically apply to those individuals who have survived SCA and their families (Figure 9).
      Figure thumbnail gr9
      Figure 9Psychological care following a sudden cardiac arrest (SCA) or a sudden unexplained death (SUD) where a genetic cause is suspected. Colors correspond to the Class of Recommendation in .
      There may be initial reluctance to seek psychological support given community stigma around mental health. Indeed, a recent study investigating families who had experienced a young SCD found that only 12% had sought psychological support, with most of those being self-referrals.
      • Karam N.
      • Jabre P.
      • Narayanan K.
      • et al.
      Psychological support and medical screening of first-degree relatives of sudden cardiac arrest victims.
      In discussing options for ongoing psychological support with patients and families, normalizing their response to a significant psychological stressor and describing common symptoms of prolonged grief and posttraumatic stress may reduce any perceived sense of stigma and increase interest in seeking support.
      A recent needs analysis of parents who had experienced the SCD of their child (including adult children) found that while medical information and support were the most important need, psychological information and support were the most unmet need.
      • McDonald K.
      • Sharpe L.
      • Yeates L.
      • Semsarian C.
      • Ingles J.
      A needs analysis of parents following sudden cardiac death in the young.
      Nearly three-quarters reported wanting access to professional counseling or psychological services. Further, many indicated access to genetic testing or understanding the genetic cause to be an important need, highlighting the importance of maintaining realistic expectations regarding the diagnostic yield of postmortem genetic testing with families.
      • Bates K.
      • Sweeting J.
      • Yeates L.
      • McDonald K.
      • Semsarian C.
      • Ingles J.
      Psychological adaptation to molecular autopsy findings following sudden cardiac death in the young.
      At present, this is likely not greater than 15%, and there is a high likelihood of uncertain genetic findings especially with increasing gene panel sizes.
      • Bagnall R.D.
      • Weintraub R.G.
      • Ingles J.
      • et al.
      A prospective study of sudden cardiac death among children and young adults.
      ,
      • Lahrouchi N.
      • Raju H.
      • Lodder E.M.
      • et al.
      Utility of post-mortem genetic testing in cases of sudden arrhythmic death syndrome.
      A Swedish study of parents whose children died suddenly between 15 and 35 years of age likewise showed a critical lack of information and support in the acute grief stage.
      • Wisten A.
      • Zingmark K.
      Supportive needs of parents confronted with sudden cardiac death: a qualitative study.
      This included a need for better communication of the postmortem examination process (how long it would take, when they would get results), time with a health professional to discuss the death, and information about the cause of death. There was a lack of psychological support in the immediate aftermath, with many family members seeking their own care, including grief counselors and support groups. The need for support in the early aftermath has been shown to be important in other studies examining suddenly bereaved parents.
      • Dent A.
      • Condon L.
      • Blair P.
      • Fleming P.
      A study of bereavement care after a sudden and unexpected death.
      ,
      • Merlevede E.
      • Spooren D.
      • Henderick H.
      • et al.
      Perceptions, needs and mourning reactions of bereaved relatives confronted with a sudden unexpected death.
      Community or peer-based bereavement support groups can also enhance social support.
      • Simon N.M.
      Treating complicated grief.
      ,
      • Steffen E.M.
      • Timotijevic L.
      • Coyle A.
      A qualitative analysis of psychosocial needs and support impacts in families affected by young sudden cardiac death: the role of community and peer support [published online ahead of print May 5, 2020].
      Peer support programs come in many different forms but always involve people with similar backgrounds providing emotional, social, or practical support to each other.
      • Solomon P.
      Peer support/peer provided services underlying processes, benefits, and critical ingredients.
      Peer supporters draw on their shared experiences to provide empathic understanding, information, and advice to those they are helping. A key aim is to promote hope, recovery from illness or trauma, improved life skills, psychological well-being, and social integration.
      • Landers G.M.
      • Zhou M.
      An analysis of relationships among peer support, psychiatric hospitalization, and crisis stabilization.
      A recent systematic review of peer support services for bereaved survivors of the sudden death of a loved one in multiple settings found evidence of reductions in grief and increased well-being and personal growth among participants, and improved personal growth and positive meaning in life among peer providers.
      • Bartone P.T.
      • Bartone J.V.
      • Violanti J.M.
      • Gileno Z.M.
      Peer support services for bereaved survivors: a systematic review.
      There is a current gap in care in addressing psychological support needs of families after the SCD of a young relative.
      Tabled 1Recommendations for psychological care
      CORLOERecommendationsReferences
      1B-NR
      • 1.
        In the investigation of SCA where a genetic cause is suspected, it is recommended that referral be offered for assessment by a health professional trained in psychological evaluation and treatment to the patient (if survived) and immediate family members.
      • Yeates L.
      • Hunt L.
      • Saleh M.
      • Semsarian C.
      • Ingles J.
      Poor psychological wellbeing particularly in mothers following sudden cardiac death in the young.
      ,
      • Ingles J.
      • Spinks C.
      • Yeates L.
      • McGeechan K.
      • Kasparian N.
      • Semsarian C.
      Posttraumatic stress and prolonged grief after the sudden cardiac death of a young relative.
      ,
      • McDonald K.
      • Sharpe L.
      • Yeates L.
      • Semsarian C.
      • Ingles J.
      A needs analysis of parents following sudden cardiac death in the young.
      ,
      • Farnsworth M.M.
      • Fosyth D.
      • Haglund C.
      • Ackerman M.J.
      When I go in to wake them ... I wonder: parental perceptions about congenital long QT syndrome.
      2aC-LD
      • 2.
        In the investigation of SUD where a genetic cause is suspected, provision of information and referral to support services such as support workers, grief counseling, and peer support services can be useful.
      • Wisten A.
      • Zingmark K.
      Supportive needs of parents confronted with sudden cardiac death: a qualitative study.
      ,
      • Solomon P.
      Peer support/peer provided services underlying processes, benefits, and critical ingredients.
      • Landers G.M.
      • Zhou M.
      An analysis of relationships among peer support, psychiatric hospitalization, and crisis stabilization.
      • Bartone P.T.
      • Bartone J.V.
      • Violanti J.M.
      • Gileno Z.M.
      Peer support services for bereaved survivors: a systematic review.
      Synopsis
      The psychological impact to the family following an SCD where a genetic cause is suspected can be significant. Although many family members will navigate their way through this traumatic experience, up to 44% may require additional psychological support from an appropriately trained health professional such as a clinical psychologist. Addressing community stigma around mental health needs to be considered and discussed with families. In addition, support services such as social workers, grief counselors, psychosocial teams, and peer support groups may be useful to many families. Whereas the evidence for psychological support is derived from studies investigating SCD where a genetic cause is suspected, it may logically apply in those families where there has been an SCA.
      Recommendation-Specific Supportive Text
      • 1. and 2. A clinical psychologist or appropriately trained health professional includes those equipped to assess and treat trauma; for example, those experienced in delivering cognitive behavioral therapies. While the evidence to date supports a need for psychological support in family members following a young SCD where a genetic cause is suspected, this may likewise be important for relatives of a patient who suffers an SCA.
        • Yeates L.
        • Hunt L.
        • Saleh M.
        • Semsarian C.
        • Ingles J.
        Poor psychological wellbeing particularly in mothers following sudden cardiac death in the young.
        ,
        • Ingles J.
        • Spinks C.
        • Yeates L.
        • McGeechan K.
        • Kasparian N.
        • Semsarian C.
        Posttraumatic stress and prolonged grief after the sudden cardiac death of a young relative.
        ,
        • Farnsworth M.M.
        • Fosyth D.
        • Haglund C.
        • Ackerman M.J.
        When I go in to wake them ... I wonder: parental perceptions about congenital long QT syndrome.
        There is a need to train personnel in psychological care for SUD and SCA, as this is an area where the need is not currently met.

      Section 6 Investigation of Sudden Death

      6.1 Investigation of Sudden Death: History—Personal and Family

      Despite being “low-tech” and inexpensive, the history, as a tool for clinical phenotyping, is the essential and fundamental basis of approaching a patient with SCA because it can guide appropriate use and interpretation of other diagnostic modalities. The history should be focused toward both the decedent proband and also the wider family for evidence of other potentially affected members prior to investigations. Surviving family members should be investigated by a multidisciplinary team within a specialist program for cardiovascular genetic disorders with the all appropriate medical, genetic, and psychological personnel and ability for comprehensive investigations
      • Fellmann F.
      • van El C.G.
      • Charron P.
      • et al.
      European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death.
      ,
      • Priori S.G.
      • Wilde A.A.
      • Horie M.
      • et al.
      HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.
      (Figure 10).
      Figure thumbnail gr10
      Figure 10Investigation of sudden unexplained death: personal and family history. Colors correspond to the Class of Recommendation in . SCD = sudden cardiac death.
      The proband age may help define potential etiologies; CPVT and long QT syndrome are typically diseases of the young, whereas coronary artery disease and cardiomyopathies become more common with age (Figure 1). Although most deaths occur at rest or during sleep,
      • Bagnall R.D.
      • Weintraub R.G.
      • Ingles J.
      • et al.
      A prospective study of sudden cardiac death among children and young adults.
      death during exertion may point to specific etiologies such as CPVT, long QT syndrome type 1, or arrhythmogenic cardiomyopathy. In addition to a detailed prior medical and medication history (including potential drugs of abuse), the decedent’s health in the 24–48 hours preceding death including the presence of any viral prodrome or fever, as well as any prescribed medication, may be relevant. Myocarditis secondary to viral infection may be associated with viral and gastrointestinal symptoms, and both Brugada syndrome and long QT syndrome may be exacerbated by specific pharmacological agents through further inhibition of ion channel function.
      • Risgaard B.
      • Winkel B.G.
      • Jabbari R.
      • et al.
      Sudden cardiac death: pharmacotherapy and proarrhythmic drugs: a nationwide cohort study in Denmark.
      Fever is a well-recognized trigger of ECG changes and arrhythmia in Brugada syndrome
      • Michowitz Y.
      • Milman A.
      • Sarquella-Brugada G.
      • et al.
      Fever-related arrhythmic events in the multicenter Survey on Arrhythmic Events in Brugada Syndrome.
      and in some long QT syndrome subtypes,
      • Amin A.S.
      • Herfst L.J.
      • Delisle B.P.
      • et al.
      Fever-induced QTc prolongation and ventricular arrhythmias in individuals with type 2 congenital long QT syndrome.