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Heart, Lung and Circulation

Epidemiology of Sudden Cardiac Death: Global and Regional Perspectives

Published:September 19, 2018DOI:https://doi.org/10.1016/j.hlc.2018.08.026
      Despite advancements in prevention and treatment, sudden cardiac death (SCD) remains a leading cause of mortality and is responsible for approximately half of all deaths from cardiovascular disease. Outcomes continue to remain poor following a sudden cardiac arrest, with most individuals not surviving. Although coronary heart disease remains the dominant underlying condition, our understanding of SCD is improving through greater knowledge of clinical risk factors, cardiomyopathies, and primary arrhythmic disorders. However, despite a growing wealth of information from studies in North America, Europe, and Japan, data from other global regions (and particularly from low-and middle-income countries) remains scarce.

      Keywords

      Introduction

      Sudden cardiac death (SCD) is a leading cause of mortality and responsible for approximately half of all deaths from cardiovascular disease [
      • Myerburg R.J.
      • Castellanos A.
      CardiacArrest and sudden cardiac death (in Braunwald's heart disease: a textbook of cardiovascular medicine).
      ]. It is generally accepted that SCD refers to an unexpected death or arrest from a cardiovascular cause. Most studies refer to SCD as a sudden death from a cardiovascular cause which occurs within one hour of symptom onset when witnessed, or if not witnessed, an unexpected death from a cardiovascular cause where the individual was observed to be alive within the previous 24 hours. However, non-cardiac causes such as pulmonary embolism, stroke, and aortic syndromes can also lead to rapid death and should be considered as alternate pathologies.
      Despite its importance and societal burden, our understanding of SCD epidemiology is limited. The epidemiological study of SCD has been particularly hampered by definitional and methodological challenges. Although much progress has been made through implantable cardioverter defibrillators, community-based cardiopulmonary resuscitation, and coronary heart disease (CHD) management, SCD still remains the cause of 15–20% of deaths in Western societies [
      • Albert C.M.
      • Chae C.U.
      • Grodstein F.
      • Rose L.M.
      • Rexrode K.M.
      • Ruskin J.N.
      • et al.
      Prospective study of sudden cardiac death among women in the United States.
      ]. Furthermore, there is a comparative dearth of information on SCD from other global regions, particularly low and-middle income countries. In this manuscript, we review the epidemiology of SCD focussing on both global and available regional data, with detail on specific conditions, risk prediction, and intervention included elsewhere in this Special Issue on Ventricular Arrhythmias and SCD.

      Regional and Global Incidence of SCD

      The following sections summarise the available data on the global and regional incidence of SCD (Figure 1). However, estimates of SCD need to be interpreted in the context of several limitations. First, utilised definitions vary from study to study, despite attempts at standardisation. Second, it can be challenging to exclude non-cardiac causes of death, particularly when complete documentation of event and background history is unavailable, and autopsies are not routinely performed. Third, data sources and methodology for case ascertainment differ widely. In particular, as SCD is often identified through emergency medical systems (EMS), regional variation in the use of EMS systems affects results. Nevertheless, interrogation of the available data still provides useful insights into SCD epidemiology despite these issues.
      Figure 1
      Figure 1Global incidence of SCD.
      Incidence demonstrated is from selected studies reporting SCD in all age groups, with the exception of India (Srivatsa 2016; ≥35 years old) and Cameroon (Bonny 2017; ≥18 years old).
      Abbreviation: SCD, sudden cardiac death.

      Australia and New Zealand

      There have been a few studies of SCD incidence in Australia and New Zealand (Table 1). The most comprehensive data is from the Aus-ROC Epistry, Aus-ROC, (the epidemiology registry of the Australian Resuscitation Outcomes Consortium)Am, which included 19,722 out-of-hospital cardiac arrest (OOHCA) cases in 2015 from seven EMS services in Australia and New Zealand. The overall incidence rate in Australia was 99.4 per 100,000 [
      • Beck B.
      • Bray J.
      • Cameron P.
      • Smith K.
      • Walker T.
      • Grantham H.
      • et al.
      Aus-ROC Steering Committee Regional variation in the characteristics, incidence and outcomes of out-of-hospital cardiac arrest in Australia and New Zealand: results from the Aus-ROC Epistry.
      ]. Another large study included 12,421 EMS-attended OOHCAs in Perth, Western Australia, estimating an incidence of 60.2 per 100,000 across all age groups. Other reports in Australia have estimated an incidence of all SCD ranging from 34.6 to 89.1 per 100,000 [
      • Cheung W.
      • Flynn M.
      • Thanakrishnan G.
      • Milliss D.M.
      • Fugaccia E.
      Survival after out-of-hospital cardiac arrest in Sydney, Australia.
      ,
      • Feng J.L.
      • Nedkoff L.
      • Knuiman M.
      • Semsarian C.
      • Ingles J.
      • Briffa T.
      • Hickling S.
      Temporal trends in sudden cardiac death from 1997 to 2010: a data linkage study.
      ,
      • Finn J.C.
      • Jacobs I.G.
      • Holman C.D.
      • Oxer H.F.
      Outcomes of out-of-hospital cardiac arrest patients in Perth, Western Australia, 1996–1999.
      ,
      • Scott I.A.
      • Fitzgerald G.J.
      Early defibrillation in out-of-hospital sudden cardiac death: an Australian experience.
      ,
      • Feng J.L.
      • Hickling S.
      • Nedkoff L.
      • Knuiman M.
      • Semsarian C.
      • Ingles J.
      • Briffa T.G.
      Sudden cardiac death rates in an Australian population: a data linkage study.
      ]. Sudden cardiac death figures in younger age groups vary from 1.1 to 8.7 per 100,000 [
      • 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.
      ,
      • Inoue M.
      • Tohira H.
      • Williams T.
      • Bailey P.
      • Borland M.
      • McKenzie N.
      • et al.
      Incidence, characteristics and survival outcomes of out-of-hospital cardiac arrest in children and adolescents between 1997 and 2014 in Perth, Western Australia.
      ,
      • Doolan A.
      • Langlois N.
      • Semsarian C.
      Causes of sudden cardiac death in young Australians.
      ], with corresponding estimates in adults over 18 years of age ranging from 102.0 to 147.8 per 100,000 [
      • Woodall J.
      • McCarthy M.
      • Johnston T.
      • Tippett V.
      • Bonham R.
      Impact of advanced cardiac life support-skilled paramedics on survival from out-of-hospital cardiac arrest in a statewide emergency medical service.
      ,
      • Jennings P.A.
      • Cameron P.
      • Walker T.
      • Bernard S.
      • Smith K.
      Out-of-hospital cardiac arrest in Victoria: rural and urban outcomes.
      ]. A few studies [
      • Crone P.D.
      Auckland ambulance Service cardiac arrest data 1991–1993.
      ,
      • Swain A.H.
      • Barry T.
      • Hoyle S.R.
      • Haywood G.
      • Cameron H.
      • Larsen P.D.
      Outcomes from out-of-hospital cardiac arrest in the Wellington region of New Zealand. Does use of the fire service make a difference?.
      ,
      • Robinson S.
      • Swain A.H.
      • Hoyle S.R.
      • Larsen P.D.
      Survival from out-of-hospital cardiac arrest in New Zealand following the 2005 resuscitation guideline changes.
      ] have suggested that the incidence of EMS-treated OOHCA is not dissimilar in New Zealand to Australia [
      • Crone P.D.
      Auckland ambulance Service cardiac arrest data 1991–1993.
      ], and the AusROC Epistry demonstrated a similar incidence of all EMS-attended OOHCAs of 105.5 per 100,000 [
      • Beck B.
      • Bray J.
      • Cameron P.
      • Smith K.
      • Walker T.
      • Grantham H.
      • et al.
      Aus-ROC Steering Committee Regional variation in the characteristics, incidence and outcomes of out-of-hospital cardiac arrest in Australia and New Zealand: results from the Aus-ROC Epistry.
      ].
      Table 1Global Incidence of Sudden Cardiac Death
      RegionCountryRegionStudy year(s)Incidence per 100,000Reference
      Australia & New ZealandAustraliaNational2015All: 99.4Beck 2018
      • Beck B.
      • Bray J.
      • Cameron P.
      • Smith K.
      • Walker T.
      • Grantham H.
      • et al.
      Aus-ROC Steering Committee Regional variation in the characteristics, incidence and outcomes of out-of-hospital cardiac arrest in Australia and New Zealand: results from the Aus-ROC Epistry.
      Australia & New ZealandAustraliaIpswich, Queensland1985–1999All: 50.6Scott 1993
      • Scott I.A.
      • Fitzgerald G.J.
      Early defibrillation in out-of-hospital sudden cardiac death: an Australian experience.
      Australia & New ZealandAustraliaPerth, Western Australia1996–1999All: 89.1Finn 2001
      • Finn J.C.
      • Jacobs I.G.
      • Holman C.D.
      • Oxer H.F.
      Outcomes of out-of-hospital cardiac arrest patients in Perth, Western Australia, 1996–1999.
      Australia & New ZealandAustraliaPerth, Western Australia1997–2010All: 60.2Bray 2014
      • Bray J.E.
      • Di Palma S.
      • Jacobs I.
      • Straney I.
      • Finn J.
      Trends in the incidence of presumed cardiac out-of-hospital cardiac arrest in Perth, Western Australia, 1997–2010.
      Australia & New ZealandAustraliaSydney, New South Wales2004–2005All: 52.6Cheung 2006
      • Cheung W.
      • Flynn M.
      • Thanakrishnan G.
      • Milliss D.M.
      • Fugaccia E.
      Survival after out-of-hospital cardiac arrest in Sydney, Australia.
      Australia & New ZealandAustraliaWestern Australia1997–2010All: 34.6Feng 2015
      • Feng J.L.
      • Nedkoff L.
      • Knuiman M.
      • Semsarian C.
      • Ingles J.
      • Briffa T.
      • Hickling S.
      Temporal trends in sudden cardiac death from 1997 to 2010: a data linkage study.
      ,
      • Feng J.L.
      • Hickling S.
      • Nedkoff L.
      • Knuiman M.
      • Semsarian C.
      • Ingles J.
      • Briffa T.G.
      Sudden cardiac death rates in an Australian population: a data linkage study.
      Australia & New ZealandAustraliaWestern Australia1997–2014< 18yo: 8.7Inoue 2017
      • Myerburg R.J.
      • Castellanos A.
      CardiacArrest and sudden cardiac death (in Braunwald's heart disease: a textbook of cardiovascular medicine).
      Australia & New ZealandAustraliaSydney, New South Wales1994–2002≤ 35yo: 1.1Doolan 2004
      • Doolan A.
      • Langlois N.
      • Semsarian C.
      Causes of sudden cardiac death in young Australians.
      Australia & New ZealandAustraliaVictoria2002–2003≥ 17yo: 147.8Jennings 2006
      • Jennings P.A.
      • Cameron P.
      • Walker T.
      • Bernard S.
      • Smith K.
      Out-of-hospital cardiac arrest in Victoria: rural and urban outcomes.
      Australia & New ZealandAustraliaQueensland2000–2002≥ 18yo: 102.0Woodall 2007
      • Woodall J.
      • McCarthy M.
      • Johnston T.
      • Tippett V.
      • Bonham R.
      Impact of advanced cardiac life support-skilled paramedics on survival from out-of-hospital cardiac arrest in a statewide emergency medical service.
      Australia & New ZealandNew ZealandNational2015All: 105.5Beck 2018
      • Beck B.
      • Bray J.
      • Cameron P.
      • Smith K.
      • Walker T.
      • Grantham H.
      • et al.
      Aus-ROC Steering Committee Regional variation in the characteristics, incidence and outcomes of out-of-hospital cardiac arrest in Australia and New Zealand: results from the Aus-ROC Epistry.
      Australia & New ZealandNew ZealandNational2006–2009≤ 40yo: 2.0Wilms 2012
      • 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.
      East AsiaJapanOsaka1998–2003≥ 18yo: 36Iwami 2007
      • Iwami T.
      • Kawamura T.
      • Hiraide A.
      • Berg R.A.
      • Hayashi Y.
      • Nishiuchi T.
      • et al.
      Effectiveness of bystander-initiated cardiac-only resuscitation for patients with out-of-hospital cardiac arrest.
      East AsiaJapanNational2005–2009All: 14.9Kitamura 2012
      • Feng J.L.
      • Hickling S.
      • Nedkoff L.
      • Knuiman M.
      • Semsarian C.
      • Ingles J.
      • Briffa T.G.
      Sudden cardiac death rates in an Australian population: a data linkage study.
      East AsiaChinaRegional2005–2006All: 41.8Hua 2009
      • Hua W.
      • Zhang L.F.
      • Wu Y.F.
      • Liu X.Q.
      • Guo D.S.
      • Zhou H.L.
      • et al.
      Incidence of sudden cardiac death in China: analysis of 4 regional populations.
      East AsiaChinaBeijing2008–2009All: 38.4Zhang 2014
      • Zhang L.
      • Li Y.
      • Zhou H.
      • Wang H.
      • Dai Y.
      • Chu L.
      • et al.
      Incidence of sudden cardiac death of urban residents in Beijing.
      East AsiaSouth KoreaNational2006–2008All: 20.1Cha 2012
      • Cha W.C.
      • Lee S.C.
      • Shin S.D.
      • Song K.J.
      • Sung A.J.
      • Hwang S.S.
      Regionalisation of out-of-hospital cardiac arrest care for patients without prehospital return of spontaneous circulation.
      South AsiaIndiaTirunelveli, South India2010–2011≥ 35yo: 39.7Srivatsa 2016
      • Srivatsa U.N.
      • Swaminathan K.
      • Sithy Athiya Munavarah K.
      • Amsterdam E.
      • Shantaraman K.
      Sudden cardiac death in South India: Incidence, risk factors and pathology.
      South East AsiaSingaporeSingapore2001–200420.9Ong 2008
      • Ong M.E.
      • Ng F.S.
      • Anushia P.
      • Tham L.P.
      • Leong B.S.
      • Ong V.Y.
      • et al.
      Comparison of chest compression only and standard cardiopulmonary resuscitation for out-of-hospital cardiac arrest in Singapore.
      North AmericaUnited StatesMultiple regions2005–2015All: 110.8Benjamin 2018
      • Benjamin E.J.
      • Virani S.S.
      • Callaway C.W.
      • Chamberlain A.M.
      • Chang A.R.
      • Cheng S.
      • et al.
      American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.
      North AmericaUnited StatesOregon2002–2003All: 53Chugh 2004
      • Chugh S.S.
      • Jui J.
      • Gunson K.
      • Stecker E.C.
      • John B.T.
      • Thompson B.
      • et al.
      Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.
      North AmericaCanadaOttawa, Canada2006–2007All: 73.6Nichol 2008
      • Nichol G.
      • Thomas E.
      • Callaway C.W.
      • Hedges J.
      • Powell J.L.
      • Aufderheide T.P.
      • et al.
      Resuscitation Outcomes Consortium Investigators: regional variation in out-of-hospital cardiac arrest incidence and outcome.
      North AmericaCanadaToronto, Canada2006–2007All: 91.6Nichol 2008
      • Nichol G.
      • Thomas E.
      • Callaway C.W.
      • Hedges J.
      • Powell J.L.
      • Aufderheide T.P.
      • et al.
      Resuscitation Outcomes Consortium Investigators: regional variation in out-of-hospital cardiac arrest incidence and outcome.
      Europe27 countries2014All: 84.0Grasner 2016
      • Grasner J.T.
      • Lefering R.
      • Koster R.W.
      • Masterson S.
      • Böttiger B.W.
      • Herlitz J.
      • et al.
      EuReCa ONE Collaborators. EuReCa ONE-27 Nations, ONE, Europe, ONE Registry: a prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe.
      EuropeFranceSaint-Etienne, France1991–1992All: 94.1Giraud 1996
      • Giraud F.
      • Rascle C.
      • Guidnand M.
      Out-of-hospital cardiac arrest: Evaluation of one year of activity in Saint-Etienne's emergency medical system using the Utstein style.
      EuropeDenmarkCopenhagen, Denmark2004–2007All: 73.8Steinmetz 2008
      • Steinmetz J.
      • Barnung S.
      • Nielsen S.L.
      • Risom M.
      • Rasmussen L.S.
      Improved survival after an out-of-hospital cardiac arrest using new guidelines.
      AfricaCameroonDouala, Cameroon2013≥ 18yo: 31.3Bonny 2017
      • Bonny A.
      • Tibazarwa K.
      • Mbouh S.
      • Wa J.
      • Fonga R.
      • Saka C.
      • Ngantcha M.
      Pan African Society of Cardiology (PASCAR) Task Force on Sudden Cardiac Death: Epidemiology of sudden cardiac death in Cameroon: the first population-based cohort survey in sub-Saharan Africa.

      East Asia

      Although there is limited data from China, the most populous country within this region, one report assessed SCD from death certificates supplemented by medical records and interviews with family, hospital personnel, or other witnesses to the death. In four distinct regional populations, these investigators found an overall incidence of 41.8 per 100,000 [
      • Hua W.
      • Zhang L.F.
      • Wu Y.F.
      • Liu X.Q.
      • Guo D.S.
      • Zhou H.L.
      • et al.
      Incidence of sudden cardiac death in China: analysis of 4 regional populations.
      ]. In Japan, a prospective, nationwide registry included all EMS-treated OOHCA (only 1.3% of all OOHCA had no resuscitation) and described a very low incidence of 14.9 per 100,000 [
      • Kitamura T.
      • Iwami T.
      • Kawamura T.
      • Nitta M.
      • Nagao K.
      • Nonogi H.
      • et al.
      Nationwide improvements in survival from out-of-hospital cardiac arrest in Japan.
      ]. Another report from Osaka, Japan, included OOHCAs of presumed cardiac origin in those ≥18 years of age, estimating an incidence of 36 per 100,000 [
      • Iwami T.
      • Kawamura T.
      • Hiraide A.
      • Berg R.A.
      • Hayashi Y.
      • Nishiuchi T.
      • et al.
      Effectiveness of bystander-initiated cardiac-only resuscitation for patients with out-of-hospital cardiac arrest.
      ]. The incidence of SCD was similarly low in South Korea, where a national database reported an incidence of 20.1 per 100,000 [
      • Cha W.C.
      • Lee S.C.
      • Shin S.D.
      • Song K.J.
      • Sung A.J.
      • Hwang S.S.
      Regionalisation of out-of-hospital cardiac arrest care for patients without prehospital return of spontaneous circulation.
      ]. Data from 10 hospitals in Taipei City, Taiwan, suggested an incidence of EMS-treated OOHCA of 28.4 per 100,000 [
      • Cha W.C.
      • Lee S.C.
      • Shin S.D.
      • Song K.J.
      • Sung A.J.
      • Hwang S.S.
      Regionalisation of out-of-hospital cardiac arrest care for patients without prehospital return of spontaneous circulation.
      ].

      South Asia

      There is minimal available data from the South Asian region. A few studies of variable methodological quality have estimated the burden of SCD in India. One using single-centre autopsy data calculated a SCD incidence in those >35 years of 39.7 per 100,000, although the degree to which this accurately reflects the community prevalence of SCD is not certain [
      • Srivatsa U.N.
      • Swaminathan K.
      • Sithy Athiya Munavarah K.
      • Amsterdam E.
      • Shantaraman K.
      Sudden cardiac death in South India: Incidence, risk factors and pathology.
      ]. Other studies have calculated SCD prevalence in India with verbal autopsies or questionnaire approaches; however, incidence was not estimated [
      • Madhavan S.R.
      • Reddy S.
      • Panuganti P.K.
      • Joshi R.
      • Mallidi J.
      • Raju K.
      • et al.
      Epidemiology of sudden cardiac death in rural South India – insights from the andhra pradesh rural health initiative.
      ,
      • Rao B.H.
      • Sastry B.K.
      • Chugh S.S.
      • Kalavakolanu S.
      • Christopher J.
      • Shangula D.
      • et al.
      Contribution of sudden cardiac death to total mortality in India – a population based study.
      ]. We are not aware of incidence data from other countries in South Asia, such as Pakistan, Bangladesh, Nepal, Sri Lanka and Bhutan.

      South East Asia

      There is a similar scarcity of community-based data on SCD incidence in South East Asia. One report from Singapore found an EMS-attended SCD incidence of 20.9 per 100,000 [
      • Ong M.E.
      • Ng F.S.
      • Anushia P.
      • Tham L.P.
      • Leong B.S.
      • Ong V.Y.
      • et al.
      Comparison of chest compression only and standard cardiopulmonary resuscitation for out-of-hospital cardiac arrest in Singapore.
      ]. Other reports in this region have estimated the incidence of sudden unexplained death syndrome in Thailand and the Philippines using questionnaires and interviews, but whether these accurately reflect community SCD across all ages is uncertain [
      • Gervacio-Domingo G.
      • Punzalan F.E.
      • Amarillo M.L.
      • Dans A.
      Sudden unexplained death during sleep occurred commonly in the general population in the Philippines: a sub study of the National Nutrition and Health Survey.
      ,
      • Tungsanga K.
      • Sriboonlue P.
      Sudden unexplained death syndrome in north-east Thailand.
      ]. We are not aware of incidence data from other countries in South East Asia, such as Malaysia and Indonesia.

      Other Global Regions

      Considerably more data on SCD is available from North American and European populations. Overall, the annual incidence of SCD appears to approximate 50 to 100 per 100,000 in the general population in these regions. The Resuscitation Outcomes Consortium (ROC) maintained a registry of OOHCA in multiple regions throughout the United States (US) from 2005 to 2015; the incidence of all EMS-assessed cardiac arrests was 110.8 per 100,000 [
      • Benjamin E.J.
      • Virani S.S.
      • Callaway C.W.
      • Chamberlain A.M.
      • Chang A.R.
      • Cheng S.
      • et al.
      American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.
      ]. In another prospective evaluation of a large population in Oregon, United States, the incidence of sudden cardiac arrest was 53 per 100,000 between 2002 and 2003; retrospective death certificate review over the same time period over-estimated this by three-fold [
      • Chugh S.S.
      • Jui J.
      • Gunson K.
      • Stecker E.C.
      • John B.T.
      • Thompson B.
      • et al.
      Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.
      ]. In Canada, the incidence has been reported to vary from 73.6 to 91.7 per 100,000 [
      • Nichol G.
      • Thomas E.
      • Callaway C.W.
      • Hedges J.
      • Powell J.L.
      • Aufderheide T.P.
      • et al.
      Resuscitation Outcomes Consortium Investigators: regional variation in out-of-hospital cardiac arrest incidence and outcome.
      ]. Other studies from Europe report similar figures; the EuReCa ONE Study included data from 27 countries in October 2014 and estimated an overall annual incidence of 84.0 per 100,000 [
      • Grasner J.T.
      • Lefering R.
      • Koster R.W.
      • Masterson S.
      • Böttiger B.W.
      • Herlitz J.
      • et al.
      EuReCa ONE Collaborators. EuReCa ONE-27 Nations, ONE, Europe, ONE Registry: a prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe.
      ]. We are aware of one prospective report from sub-Saharan Africa; in Douala, Cameroon, it was estimated that SCD incidence was 33.6 per 100,000 through a three-level case reporting and ascertainment system [
      • Bonny A.
      • Tibazarwa K.
      • Mbouh S.
      • Wa J.
      • Fonga R.
      • Saka C.
      • Ngantcha M.
      Pan African Society of Cardiology (PASCAR) Task Force on Sudden Cardiac Death: Epidemiology of sudden cardiac death in Cameroon: the first population-based cohort survey in sub-Saharan Africa.
      ]. There is a paucity of data from other less developed regions of the world; although there are some reports on SCD using autopsy, in-hospital, and defibrillator information, these are insufficient to estimate the true incidence of SCD in these regions [
      • Vedanthan R.
      • Fuster V.
      • Fischer A.
      Sudden cardiac death in low- and middle-income countries.
      ,
      • 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.
      ].

      Outcomes Following SCD

      Outcomes following OOHCA remain poor despite efforts to progress cardiopulmonary resuscitation (CPR) and post-resuscitation care. In the AusROC Epistry in Australia and New Zealand, immediate post-event survival was 28% (range 21–36%) in cases of attempted resuscitation, but only 12% (range 9–17%) survived to hospital discharge or to 30 days [
      • Beck B.
      • Bray J.
      • Cameron P.
      • Smith K.
      • Walker T.
      • Grantham H.
      • et al.
      Aus-ROC Steering Committee Regional variation in the characteristics, incidence and outcomes of out-of-hospital cardiac arrest in Australia and New Zealand: results from the Aus-ROC Epistry.
      ]. Survival rates appear to be significantly lower in other Asia Pacific countries, with the PAROS (Pan-Asian Resuscitation Outcomes Study) reporting survival to hospital discharge rates of non-traumatic arrests as being 5.6% in Japan, 9.9% in Korea, 1.0% in Malaysia, 2.5% in Singapore, 2.7% in Thailand, and 4.8% in Taiwan [
      • Ong M.E.
      • Shin S.D.
      • De Souza N.N.
      • Tanaka H.
      • Nishiuchi T.
      • Song K.J.
      • et al.
      PAROS Clinical Research Network: Outcomes for out-of-hospital cardiac arrests across 7 countries in Asia: The Pan Asian Resuscitation Outcomes Study (PAROS).
      ]. This study also included the United Arab Emirates, who reported a survival to hospital discharge rate of 2.8% [
      • Ong M.E.
      • Shin S.D.
      • De Souza N.N.
      • Tanaka H.
      • Nishiuchi T.
      • Song K.J.
      • et al.
      PAROS Clinical Research Network: Outcomes for out-of-hospital cardiac arrests across 7 countries in Asia: The Pan Asian Resuscitation Outcomes Study (PAROS).
      ]. In the United States, survival to hospital discharge after EMS-treated OOHCA in 2015 was 12.4% in the ROC registry [
      • Benjamin E.J.
      • Virani S.S.
      • Callaway C.W.
      • Chamberlain A.M.
      • Chang A.R.
      • Cheng S.
      • et al.
      American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.
      ]. Similar survival rates appear to exist in Europe; the EuReCa ONE Study reported an overall survival rate of 10.3% to hospital discharge or 30 days [
      • Grasner J.T.
      • Lefering R.
      • Koster R.W.
      • Masterson S.
      • Böttiger B.W.
      • Herlitz J.
      • et al.
      EuReCa ONE Collaborators. EuReCa ONE-27 Nations, ONE, Europe, ONE Registry: a prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe.
      ].

      Trends in Incidence, Rhythm and Survival

      Most of the available data seem to support a declining incidence of SCD in recent years. For example, several studies from Western Australia have reported that age-standardised rates of SCD decreased in the late 1990s and early 2000s. However, more contemporary data now raised the possibility of a potential increase in recent years [
      • Bray J.E.
      • Di Palma S.
      • Jacobs I.
      • Straney I.
      • Finn J.
      Trends in the incidence of presumed cardiac out-of-hospital cardiac arrest in Perth, Western Australia, 1997–2010.
      ,
      • Feng J.L.
      • Nedkoff L.
      • Knuiman M.
      • Semsarian C.
      • Ingles J.
      • Briffa T.
      • Hickling S.
      Temporal trends in sudden cardiac death from 1997 to 2010: a data linkage study.
      ,
      • Beck B.
      • Tohira H.
      • Bray J.E.
      • Straney L.
      • Brown E.
      • Inoue M.
      • et al.
      Trends in traumatic out-of-hospital cardiac arrest in Perth, Western Australia from 1997 to 2014.
      ]. Similarly, the incidence of OOHCA <18 years of age has been reported to have decreased from 14.1 (1997–2000) to 8.7 (2011–2014) per 100,000 in Perth, Western Australia [
      • Inoue M.
      • Tohira H.
      • Williams T.
      • Bailey P.
      • Borland M.
      • McKenzie N.
      • et al.
      Incidence, characteristics and survival outcomes of out-of-hospital cardiac arrest in children and adolescents between 1997 and 2014 in Perth, Western Australia.
      ]. Sudden cardiac death rates have also been observed to have declined elsewhere, including in Sweden, Netherlands, and Japan [
      • Messner T.
      • Lundberg V.
      Trends in sudden cardiac death in the northern Sweden MONICA area 1985–1999.
      ,
      • Niemeijer M.N.
      • van den Berg M.E.
      • Leening M.J.
      • Hofman A.
      • Franco O.H.
      • Deckers J.W.
      • et al.
      Declining incidence of sudden cardiac death from 1990–2010 in a general middle-aged and elderly population: the Rotterdam study.
      ,
      • Maruyama M.
      • Ohira T.
      • Imano H.
      • Kitamura A.
      • Kiyama M.
      • Okada T.
      • et al.
      Trends in sudden cardiac death and its risk factors in Japan from 1981 to 2005: the Circulatory Risk in Communities Study (CIRCS).
      ]. The Framingham Investigators have also described a 49% decrease in SCD from 1950–1959 to 1990–1999 in the United States [
      • Fox C.S.
      • Evans J.C.
      • Larson M.G.
      • Kannel W.B.
      • Levy D.
      Temporal trends in coronary heart disease mortality and sudden cardiac death from 1950 to 1999: the Framingham Heart Study.
      ]. Although the US ROC registry has reported an increase in the rate of EMS-treated OOHCA from 47.1 per 100,000 in 2008 to 66.0 per 100,000 in 2015, this may reflect greater treatment of OOHCA rather than a true increase in overall incidence [
      • Benjamin E.J.
      • Virani S.S.
      • Callaway C.W.
      • Chamberlain A.M.
      • Chang A.R.
      • Cheng S.
      • et al.
      American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.
      ]. Trends in the incidence rates in other regions of the world, particularly low and middle income countries, is less certain.
      In addition to quality CPR, the rhythm on first assessment has a significant influence on outcome. For example, in the ROC registry, survival rates were significantly higher if the first rhythm was shockable (30.2%) or layperson-initiated CPR occurred (43.6%) [
      • Benjamin E.J.
      • Virani S.S.
      • Callaway C.W.
      • Chamberlain A.M.
      • Chang A.R.
      • Cheng S.
      • et al.
      American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.
      ]. In the Cardiac Arrest Registry to Enhance Survival (CARES) in the US, automated external defibrillator (AED) use and bystander CPR explained as much as 50.4% of survival variation across 132 counties [
      • Beck B.
      • Bray J.
      • Cameron P.
      • Smith K.
      • Walker T.
      • Grantham H.
      • et al.
      Aus-ROC Steering Committee Regional variation in the characteristics, incidence and outcomes of out-of-hospital cardiac arrest in Australia and New Zealand: results from the Aus-ROC Epistry.
      ]. Thus, trends in the first detected rhythm are of great importance to understanding and subsequently attempting to reduce SCD. Data from North America and Europe suggest that ventricular fibrillation (VF) as the first rhythm has declined between 1980 and 2000 [
      • Cobb L.A.
      • Fahrenbruch C.E.
      • Olsufka M.
      • Copass M.K.
      Changing incidence of out-of-hospital ventricular fibrillation, 1980–2000.
      ,
      • Herlitz J.
      • Andersson E.
      • Bång A.
      • Engdahl J.
      • Holmberg M.
      • Lindqvist J.
      • et al.
      Experiences from treatment of out-of-hospital cardiac arrest during 17 years in Goteborg.
      ,
      • Kuisma M.
      • Repo J.
      • Alaspåå A.
      The incidence of out-of-hospital ventricular fibrillation in Helsinki, Finland, from 1994 to 1999.
      ]. These trends may have plateaued in recent years, with the ROC registry describing the proportion of shockable rhythms ranging from 20.2 to 21.9% between 2007 and 2015 [
      • Benjamin E.J.
      • Virani S.S.
      • Callaway C.W.
      • Chamberlain A.M.
      • Chang A.R.
      • Cheng S.
      • et al.
      American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.
      ]. A variety of explanations has been proffered for the initial increase and subsequent maintenance of a majority of cases where asystole or pulseless electrical activity (PEA) is the first rhythm, including a greater proportion of unwitnessed arrests at home, increasing use of beta blockers and implantable defibrillators in high risk patients, and older patients who may have other non-cardiac precipitants leading to PEA [
      • Hayashi M.
      • Shimizu W.
      • Albert C.M.
      The spectrum of epidemiology underlying sudden cardiac death.
      ]. There is less data on temporal trends in first rhythm from other regions; however, reports suggest that geographic variation in the proportion of shockable rhythms exist. For example, the AusROC registry has described that 28% of arrest demonstrated a shockable rhythm in Australia and New Zealand [
      • Beck B.
      • Bray J.
      • Cameron P.
      • Smith K.
      • Walker T.
      • Grantham H.
      • et al.
      Aus-ROC Steering Committee Regional variation in the characteristics, incidence and outcomes of out-of-hospital cardiac arrest in Australia and New Zealand: results from the Aus-ROC Epistry.
      ]. However, the PAROS study reported a much lower proportion of shockable rhythms of between 4.1% and 18.7% of arrests in the Asia Pacific [
      • Ong M.E.
      • Shin S.D.
      • De Souza N.N.
      • Tanaka H.
      • Nishiuchi T.
      • Song K.J.
      • et al.
      PAROS Clinical Research Network: Outcomes for out-of-hospital cardiac arrests across 7 countries in Asia: The Pan Asian Resuscitation Outcomes Study (PAROS).
      ].
      In response to efforts to improve CPR and post resuscitation care, survival rates are increasing, but overall remain low. In Perth, Western Australia, survival to hospital discharge appeared to increase from 7.3% in 1997 to 12.0% in 2010 [
      • Bray J.E.
      • Di Palma S.
      • Jacobs I.
      • Straney I.
      • Finn J.
      Trends in the incidence of presumed cardiac out-of-hospital cardiac arrest in Perth, Western Australia, 1997–2010.
      ]. Data from the ROC registry in the United States show that survival to hospital discharge increased from 10.2% to 12.4% between 2006 and 2015 [
      • Benjamin E.J.
      • Virani S.S.
      • Callaway C.W.
      • Chamberlain A.M.
      • Chang A.R.
      • Cheng S.
      • et al.
      American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.
      ]. In Denmark, 30-day survival similarly increased from 3.5% to 10.8% between 2001 and 2010 [
      • Wissenberg M.
      • Lippert F.K.
      • Folke F.
      • Weeke P.
      • Hansen C.M.
      • Christensen E.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.
      ]. In Japan, survival also appears to be increasing to some extent. In one study, 30-day survival with favourable neurological outcome increased from 1.6% in 2005 to 2.8% in 2009 [
      • Kitamura T.
      • Iwami T.
      • Kawamura T.
      • Nitta M.
      • Nagao K.
      • Nonogi H.
      • et al.
      Nationwide improvements in survival from out-of-hospital cardiac arrest in Japan.
      ]. In South Korea, survival to discharge increased in metropolitan areas (3.6% in 2006 to 5.3% in 2010) but interestingly remained low in rural areas (0.5% in 2006 to 0.8% in 2010) [
      • Ro Y.S.
      • Shin S.D.
      • Song K.J.
      • Lee E.J.
      • Kim J.Y.
      • Ahn K.O.
      • et al.
      A trend in epidemiology and outcomes of out-of-hospital cardiac arrest by urbanization level: a nationwide observational study from 2006 to 2010 in South Korea.
      ]. However, data on survival trends from other regions, again particularly from low and middle income countries, remains scarce.

      SCD Risk Factors

      Age, Sex and Ethnicity

      The majority of SCD occurs in the adult population in whom the incidence of SCD rises with increasing age (Figure 2 and Table 2) [
      • Albert C.M.
      • Chae C.U.
      • Grodstein F.
      • Rose L.M.
      • Rexrode K.M.
      • Ruskin J.N.
      • et al.
      Prospective study of sudden cardiac death among women in the United States.
      ,
      • Chugh S.S.
      • Jui J.
      • Gunson K.
      • Stecker E.C.
      • John B.T.
      • Thompson B.
      • et al.
      Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.
      ]. Amongst individuals under 35 years of age, the highest incidence is observed in the 0–5 year age group [
      • Chugh S.S.
      • Jui J.
      • Gunson K.
      • Stecker E.C.
      • John B.T.
      • Thompson B.
      • et al.
      Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.
      ]. Data suggest that men have a three- to four-fold higher risk for SCD compared to women, although recent studies suggest this disparity may be declining [
      • Chugh S.S.
      • Jui J.
      • Gunson K.
      • Stecker E.C.
      • John B.T.
      • Thompson B.
      • et al.
      Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.
      ]. It is well-established that individuals of African-American descent appear to have a higher rates of SCD and poorer outcomes compared to those of Caucasian or Hispanic descent [
      • Shah K.S.
      • Shah A.S.
      • Bhopal R.
      Systematic review and meta-analysis of out-of-hospital cardiac arrest and race or ethnicity: black US populations fare worse.
      ]. Although there are few multi-ethnic studies, some data suggest that the incidence of SCD is lower in Asian individuals which is consistent with population estimates from Asian regions discussed above [
      • Zheng Z.J.
      • Croft J.B.
      • Giles W.H.
      • Mensah G.A.
      Sudden cardiac death in the United States, 1989 to 1998.
      ].
      Figure 2
      Figure 2Age and Gender Distribution of SCD.
      Adapted with permission from Chugh et al., Journal of the American College of Cardioogy, 2004
      [
      • Rao B.H.
      • Sastry B.K.
      • Chugh S.S.
      • Kalavakolanu S.
      • Christopher J.
      • Shangula D.
      • et al.
      Contribution of sudden cardiac death to total mortality in India – a population based study.
      ]
      .
      Table 2Selected risk factors for Sudden Cardiac Death
      Demographics
      – Increasing age

      – Male gender

      – African-American or non-Asian ethnicity
      Coronary heart disease risk factors
      – Hypertension

      – Diabetes

      – Dyslipidaemia

      – Cigarette smoking

      – Obesity
      Electrocardiographic parameters
      – Heart rate

      – QRS duration or fragmentation

      – Q waves or dynamic ST segment changes

      – QTc interval

      – QRS-T angle

      – QRS transition zone

      – T-peak-to-T-end interval

      – Increased R wave voltage

      – Specific abnormalities associated with primary arrhythmic disorders
      Lifestyle/psychosocial factors
      – Depression and anxiety

      – Diet (greater fish, n-3 fatty polyunsaturated acids, Mediterranean diet protective)

      – Heavy alcohol use

      – Limited physical activity
      Genetics
      – Family history of sudden cardiac death

      – Specific mutations/polymorphisms
      Specific conditions
      – Coronary heart disease

      – Atrial fibrillation

      – Chronic kidney disease

      – Obstructive sleep apnoea

      – Dilated cardiomyopathies

      – Hypertrophic cardiomyopathy

      – Arrhythmogenic right ventricular dysplasia

      – Infiltrative diseases (e.g. sarcoidosis, amyloidosis)

      – Valvular heart disease

      – Congenital abnormalities
      Inherited arrhythmic syndromes
      – Long and short QT syndromes

      – Brugada syndrome

      – Catecholaminergic polymorphic ventricular tachycardia

      – Early repolarisation syndrome

      Clinical Risk Factors

      Several other clinical risk factors have been associated with SCD in epidemiologic studies. Coronary heart disease risk factors including hypertension, diabetes, dyslipidaemia, cigarette smoking, and obesity are predictive of SCD in men and in women [
      • Albert C.M.
      • Chae C.U.
      • Grodstein F.
      • Rose L.M.
      • Rexrode K.M.
      • Ruskin J.N.
      • et al.
      Prospective study of sudden cardiac death among women in the United States.
      ,
      • Adabag A.S.
      • Luepker R.V.
      • Roger V.L.
      • Gersh B.J.
      Sudden cardiac death: epidemiology and risk factors.
      ]. Somewhat unexpectedly, this is also the case amongst the young; 58% of subjects aged 5 to 34 years of age who experienced SCD in the Oregon Sudden Cardiac Death Study had at least one cardiovascular risk factor [
      • Jayaraman R.
      • Reinier K.
      • Nair S.
      • Aro A.L.
      • Uy-Evanado A.
      • Rusinaru C.
      • et al.
      Risk factors of sudden cardiac death in the young: multiple-year community-wide assessment.
      ]. Moreover, there was a 39% prevalence of obesity in these young individuals [
      • Jayaraman R.
      • Reinier K.
      • Nair S.
      • Aro A.L.
      • Uy-Evanado A.
      • Rusinaru C.
      • et al.
      Risk factors of sudden cardiac death in the young: multiple-year community-wide assessment.
      ]. Family history of SCD may also represent a risk factor for SCD [
      • Friedlander Y.
      • Siscovick D.S.
      • Weinmann S.
      • Austin M.A.
      • Psaty B.M.
      • Lemaitre R.N.
      • et al.
      Family history as a risk factor for primary cardiac arrest.
      ]. More recent data suggest other clinical comorbidities may be associated with subsequent SCD, including atrial fibrillation, chronic kidney disease, and obstructive sleep apnoea [
      • Chen L.Y.
      • Sotoodehnia N.
      • Bůžková P.
      • Lopez F.L.
      • Yee L.M.
      • Heckbert S.R.
      • et al.
      Atrial fibrillation and the risk of sudden cardiac death: the atherosclerosis risk in communities study and cardiovascular health study.
      ,
      • Deo R.
      • Norby F.L.
      • Katz R.
      • Sotoodehnia N.
      • Adabag S.
      • DeFilippi C.R.
      • et al.
      Development and validation of a sudden cardiac death prediction model for the general population.
      ,
      • Gami A.S.
      • Olson E.J.
      • Shen W.K.
      • Wright R.S.
      • Ballman K.V.
      • Hodge D.O.
      • et al.
      Obstructive sleep apnea and the risk of sudden cardiac death: a longitudinal study of 10,701 adults.
      ]. Serious mental illnesses, such as depression, anxiety, and psychosis, have also been linked to SCD [
      • Hayashi M.
      • Shimizu W.
      • Albert C.M.
      The spectrum of epidemiology underlying sudden cardiac death.
      ]. Lifestyle factors may also play a role in predisposing to SCD. Dietary patterns including greater fish, n-3 polyunsaturated fatty acids, magnesium and a Mediterranean-style diet appear to be protective [
      • Albert C.M.
      • Hennekens C.H.
      • O'Donnell C.J.
      • Ajani U.A.
      • Carey V.J.
      • Willett W.C.
      • et al.
      Fish consumption and risk of sudden cardiac death.
      ,
      • Chiuve S.E.
      • Fung T.T.
      • Rexrode K.M.
      • Spiegelman D.
      • Manson J.E.
      • Stampfer M.J.
      • Albert C.M.
      Adherence to a low-risk, healthy lifestyle and risk of sudden cardiac death among women.
      ]. Heavy alcohol use appears to be harmful, with some data suggesting small-to-moderate alcohol intake potentially conferring a reduced risk [
      • Chiuve S.E.
      • Rimm E.B.
      • Mukamal K.J.
      • Rexrode K.M.
      • Stampfer M.J.
      • Manson J.E.
      • Albert C.M.
      Light-to-moderate alcohol consumption and risk of sudden cardiac death in women.
      ]. Other studies point to the role of potential triggers such as emotional stress, air pollution, and diurnal/seasonal variation [
      • Hayashi M.
      • Shimizu W.
      • Albert C.M.
      The spectrum of epidemiology underlying sudden cardiac death.
      ,
      • Dennekamp M.
      • Akram M.
      • Abramson M.J.
      • Tonkin A.
      • Sim M.R.
      • Fridman M.
      • Erbas B.
      Outdoor air pollution as a trigger for out-of-hospital cardiac arrests.
      ]. Finally, despite vigorous exercise being a possible trigger, most studies support regular physical activity lowering the risk of SCD [
      • Whang W.
      • Manson J.E.
      • Hu F.B.
      • Chae C.U.
      • Rexrode K.M.
      • Willett W.C.
      • et al.
      Physical exertion, exercise, and sudden cardiac death in women.
      ].

      Electrocardiographic Parameters

      Electrocardiogram (ECG) parameters may represent intermediate phenotypes related to clinical risk factors and/or reflect the presence of structural heart disease or an arrhythmic syndrome. Several ECG parameters, including greater resting heart rate and markers of abnormal cardiac depolarisation and repolarisation, have been previously associated with a risk of SCD, as have specific abnormalities associated with primary arrhythmic disorders (e.g. long and short QT syndromes, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy (ARVC), and Wolff-Parkinson-White syndrome) [
      • Adabag A.S.
      • Luepker R.V.
      • Roger V.L.
      • Gersh B.J.
      Sudden cardiac death: epidemiology and risk factors.
      ]. More recently, combinations of ECG parameters reflecting different aspects of cardiac electrophysiology have been utilised to predict SCD risk. Using data from the Oregon Sudden Cardiac Death Study, ECG parameters which remained predictive of SCD in the final model included heart rate, left ventricular (LV) hypertrophy, QRS transition zone, QRS-T angle QTc and T-peak-to-T-end [
      • Aro A.L.
      • Reinier K.
      • Rusinaru C.
      • Uy-Evanado A.
      • Darouian N.
      • Phan D.
      • et al.
      Electrical risk score beyond the left ventricular ejection fraction: prediction of sudden cardiac death in the Oregon Sudden Unexpected Death Study and the Atherosclerosis Risk in Communities Study.
      ].

      Coronary Heart Disease

      Sudden cardiac death accounts for approximately half of all CHD-related deaths in the United States, and CHD is thought to be the structural basis for approximately 70% of all SCD, however the latter proportion is known to vary by age, gender, race, and ethnicity (Figure 3) [
      • Myerburg R.J.
      • Castellanos A.
      CardiacArrest and sudden cardiac death (in Braunwald's heart disease: a textbook of cardiovascular medicine).
      ]. Even amongst the young, CHD is a relatively common cause of SCD. In the Oregon Sudden Cardiac Death Study, CHD was the second most common condition (22%) underlying SCD among subjects aged 5 to 34 years [
      • Jayaraman R.
      • Reinier K.
      • Nair S.
      • Aro A.L.
      • Uy-Evanado A.
      • Rusinaru C.
      • et al.
      Risk factors of sudden cardiac death in the young: multiple-year community-wide assessment.
      ]. The spectrum of substrates underlying CHD-related SCD include transient ischaemia, acute coronary syndromes, scar-related pathophysiology, and ischaemic cardiomyopathies [
      • Myerburg R.J.
      • Junttila M.J.
      Sudden cardiac death caused by coronary heart disease.
      ]. The risk of SCD is greatest in the first month following a myocardial infarction and decreases over time, although those who develop ventricular remodelling and heart failure have a subsequent increase in risk [
      • Adabag A.S.
      • Therneau T.M.
      • Gersh B.J.
      • Weston S.A.
      • Roger V.L.
      Sudden death after myocardial infarction.
      ]. However, two-thirds of CHD-related SCD occurs as either the first clinical manifestation of CHD or in supposedly low-risk individuals based on current risk prediction methods, thwarting efforts to reduce the burden of CHD-related SCD [
      • Myerburg R.J.
      • Junttila M.J.
      Sudden cardiac death caused by coronary heart disease.
      ]. Although data is limited from other regions of the world, it may be reasonable to predict that the proportion of CHD-related SCD may parallel the incidence of CHD mortality as it has in Western countries [
      • Adabag A.S.
      • Therneau T.M.
      • Gersh B.J.
      • Weston S.A.
      • Roger V.L.
      Sudden death after myocardial infarction.
      ]. Supporting this fact is data demonstrating that CHD is the basis for only 25–50% of SCD in Japan, commensurate with known lower CHD incidence and mortality [
      • Maruyama M.
      • Ohira T.
      • Imano H.
      • Kitamura A.
      • Kiyama M.
      • Okada T.
      • et al.
      Trends in sudden cardiac death and its risk factors in Japan from 1981 to 2005: the Circulatory Risk in Communities Study (CIRCS).
      ,
      • Ikeda T.
      • Yusu S.
      • Nakamura K.
      • Yoshino H.
      Risk stratification for sudden cardiac death.
      ]. It is therefore likely that wide variation in CHD-related SCD exists, as it does with CHD, with possibly high rates in regions such as Central Asia, Oceania and Eastern Europe [
      • Roth G.A.
      • Huffman M.D.
      • Moran A.E.
      • Feigin V.
      • Mensah G.A.
      • Naghavi M.
      • Murray C.J.
      Global and regional patterns in cardiovascular mortality from 1990 to 2013.
      ].

      Other Structural Heart Disease

      Approximately 15% of overall SCD occurs in patients with other non-ischaemic structural heart disease in Western society [
      • Chugh S.S.
      • Jui J.
      • Gunson K.
      • Stecker E.C.
      • John B.T.
      • Thompson B.
      • et al.
      Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.
      ,
      • Zheng Z.J.
      • Croft J.B.
      • Giles W.H.
      • Mensah G.A.
      Sudden cardiac death in the United States, 1989 to 1998.
      ]. This category encompasses dilated cardiomyopathies, hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, infiltrative diseases (sarcoidosis, amyloidosis), valvular heart disease, and congenital abnormalities. The proportion of SCD caused by non-ischaemic cardiomyopathies is greater in younger age groups, and estimated to be 15–30% of SCD in those <35 years of age [
      • Hayashi M.
      • Shimizu W.
      • Albert C.M.
      The spectrum of epidemiology underlying sudden cardiac death.
      ,
      • Puranik R.
      • Chow C.K.
      • Duflou J.A.
      • Kilborn M.J.
      • McGuire M.A.
      Sudden death in the young.
      ]. Moreover, in regions where CHD-related SCD is lower than in Western countries, other forms of structural heart disease may account for a greater proportion of SCD. For example, it has been estimated in Japan that cardiomyopathies account for 30–35% of SCD [
      • Ikeda T.
      • Yusu S.
      • Nakamura K.
      • Yoshino H.
      Risk stratification for sudden cardiac death.
      ]. It should also be noted that, even in the absence of macroscopic structural heart disease, histologic examination can reveal the presence of concealed substrates such as focal myocarditis and regional ARVC [
      • Corrado D.
      • Basso C.
      • Thiene G.
      Sudden cardiac death in young people with apparently normal heart.
      ]. Moreover, this category may expand as further research uncovers a structural basis for SCD of previously uncertain cause. As one example, recent evidence supports a high prevalence of mitral valve prolapse in unexplained SCD and stretch-induced fibrosis as a concealed substrate in these individuals following previously anecdotal associations [
      • Basso C.
      • Perazzolo Marra M.
      • Rizzo S.
      • De Lazzari M.
      • Giorgi B.
      • Cipriani A.
      • et al.
      Arrhythmic mitral valve prolapse and sudden cardiac death.
      ,
      • Nalliah C.J.
      • Mahajan R.
      • Elliott A.D.
      • Haqqani H.
      • Lau D.H.
      • Vohra J.K.
      • Morton J.B.
      • Semsarian C.
      • Marwick T.
      • Kalman J.M.
      • Sanders P.
      Mitral valve prolapse and sudden cardiac death: a systematic review and meta-analysis.
      ].

      Inherited Arrhythmic Disorders

      In those with unexplained arrhythmic cardiac arrest not attributable to CHD or other disease, systematic testing reveals a potential cause in approximately 50%, of which two-thirds are primary arrhythmic disorders and the remaining have unrecognised structural disease [
      • Krahn A.D.
      • Healey J.S.
      • Chauhan V.
      • Birnie D.H.
      • Simpson C.S.
      • Champagne J.
      • et al.
      Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER).
      ]. Arrhythmic disorders include long and short QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and early repolarisation syndrome. Overall, it is thought that arrhythmic disorders account for 1–2% of all SCD in Western countries [
      • Hayashi M.
      • Shimizu W.
      • Albert C.M.
      The spectrum of epidemiology underlying sudden cardiac death.
      ]. However, there is data to suggest that geographic and possibly ethnic variation exists in these genetic disorders. For example, the prevalence of Brugada syndrome appears to be greater in Asian (9 per 1000) compared to European (3 per 1000) and North American (2 per 1000) populations [
      • Quan X.Q.
      • Li S.
      • Liu R.
      • Zheng K.
      • Wu X.F.
      • Tang Q.
      A meta-analytic review of prevalence for Brugada ECG patterns and the risk for death.
      ]. Reports also suggest that early repolarisation is more common in African Americans than in individuals of Asian or Caucasian descent [
      • Walsh 3rd, J.A.
      • Ilkhanoff L.
      • Soliman E.Z.
      • Prineas R.
      • Liu K.
      • Ning H.
      • Lloyd-Jones D.M.
      Natural history of the early repolarization pattern in a biracial cohort: CARDIA (Coronary Artery Risk Development in Young Adults) Study.
      ,
      • Haruta D.
      • Matsuo K.
      • Tsuneto A.
      • Ichimaru S.
      • Hida A.
      • Sera N.
      • et al.
      Incidence and prognostic value of early repolarization pattern in the 12-lead electrocardiogram.
      ]. In contrast, the prevalence of long QT syndrome has been reported to be similar in Caucasian, Japanese, and Korean populations (0.5 per 1000) [
      • Schwartz P.J.
      • Stramba-Badiale M.
      • Crotti L.
      • Pedrazzini M.
      • Besana A.
      • Bosi G.
      • et al.
      Prevalence of the congenital long-QT syndrome.
      ,
      • Hayashi K.
      • Fujino N.
      • Uchiyama K.
      • Ino H.
      • Sakata K.
      • Konno T.
      • et al.
      Long QT syndrome and associated gene mutation carriers in Japanese children: results from ECG screening examinations.
      ,
      • Uhm J.S.
      • Hwang I.U.
      • Oh Y.S.
      • Choi M.S.
      • Jang S.W.
      • Shin W.S.
      • et al.
      Prevalence of electrocardiographic findings suggestive of sudden cardiac death risk in 10,867 apparently healthy young Korean men.
      ].

      Conclusions

      Although data from many regions of the world is limited, SCD remains a major public health burden worldwide. Improving our understanding of risk factors and underlying conditions, and how these vary across regional populations and ethnicities, may offer new opportunities for prevention and treatment. Further study on the global and regional epidemiology of SCD is thus urgently required to reduce the societal burden of premature demise from SCD.

      Sources of Funding

      Dr Wong is supported by a Neil Hamilton Farley Early Career Fellowship from the National Health and Medical Research Council of Australia (NHMRC) . Dr Lau is supported by the Robert J. Craig Lectureship from the University of Adelaide . Dr Brown is supported by a NHMRC Senior Research Fellowship . Drs Kalman and Sanders are supported by Practitioner Fellowships from the NHMRC . Dr Sanders is supported by the National Heart Foundation of Australia .

      Disclosures

      Dr Wong reports having received lecture and/or travel funding from Novartis, Servier, Boehringer-Ingelheim and Medtronic. Dr. Albert reports research grants from the NIH, Abbott, Roche, and St. Jude Medical. Dr Sanders reports having served on the advisory board of Medtronic, Abbott and CathRx. Dr Sanders reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, St Jude Medical, Boston Scientific. Dr Sanders reports that the University of Adelaide has received on his behalf research funding from Medtronic, Abbott, Boston Scientific, and Liva Nova.

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