NASPE PLENARY LECTURE 2000Sudden Cardiac Death:Exploring the Limits of Our KnowledgeROBERT J. MYERBURG, M.D.From the Division of Cardiology, University of Miami Scho ol of Medicine, Miami, Flo ridaSudden Cardiac Death. Despite progress in epidemiology, clinical pro ling, and in terventions,sudden cardiac dea th remains a m ajor clinical and public health proble m. There remain im portantunresolved issues that are c hallenges for future progress. Among these are a better understandingof the magnitude of the problem and methods of pro ling risk for indiv iduals, the etiology andmechanisms of cardiac arrest i n individuals with and without previously identi ed structural heartdisease, clinical strategies for primary and seconda ry preventi on of sudden cardi ac death, andfurther developme nt of community prog rams for improving cardiac arrest survival in the out-of-hospital environment. Each of these a reas of endeavor and potential progress are reviewed anddiscussed.(J Cardiovas c Electrophysiol, Vol. 12, pp. 369-381, March 2001)implanta ble de brillato rs, out-o f-hospit al c ardiac arrest, auto mated external de brillators, risk factors,geneticsIntroductionThe second half of the twentieth century was a wa-tershed of progress in the medical sciences. Amon g thesuccesses in the v arious disciplines of cardiov ascularmedicine was the evolution of a knowle dge base forunderstan ding causes and mechanisms of sudden cardiacdeath (SCD) and t he development of clinical strategiesfor intervention. Beginning with litt le more than a g en-eral a ppreciat ion of an association between arterioscle-rotic cardiovascular disease and SCD in the m iddle partof the century,1 - 3a series of cognitive and technologicaladvances followed upon one another, leading to mean-ingful insights and interventio n strategies by the end ofthe century. With the dawn of the twenty- rst century,the term “prevention of SCD” has begun to take on morethan theoretical meaning.Despite the series of successes, there sti ll remainimportant unresolved issues. T he limits of the progressachieved de ne the challenges that remain for the future.These can by analyzed in the context o f new insightsrequired from the underly ing ba sic and clinical sciences,the strategies neede d for further progress in prevention,and the identi cation of reasonable expectations for im-proving outcomes.The challenges begin with a more p recise de nition ofthe incidence of SCD and move to epidemiologic strat-egies that will predict fata l arrhythmic events more pre-cisely. Beyond these, the development of better treat-ment strategies for indiv iduals at risk must be so ught, aswell as more compre hensive and effective com munityintervent ion systems. New paradigms of predicting riskswill have to integrate the various disciplines and inter-vention s that may lead to red uction s in the risk of SCD,combinin g both clinical strateg ies and commun ity-basedactions. Undoubtedly, progress will be incremen tal andcumulati ve; it is unrealistic to consider that a singlestrategic ap proach wi ll have a meaningful impact on thecomplexi ties of SC D.Epidemio logy of SCD:Population and Clinical PerspectivesThe magnitud e of SCD as a public heath problem isself-eviden t, but the precise incidence remains uncertain.For more t han 20 years, SCD has been stated to have anincidenc e of 300,000 deaths annually in the UnitedStates, with other estimates ranging from as low asDr. Myerburg is funded in part by the Louis Lemberg Chair in Cardi-ology and the American Heart Association Chair in CardiovascularResearch at the University of Miami, Miami, Florida, and by GrantHL21735 from the National Heart, Lung, and Blood Institute, NationalInstitutes of Health.Address for correspondence: Robert J. Myerburg, M.D., Divisionof Cardiology, University of Miami School of Medicine, P.O.Box 016960, Miami, FL 33101. Fax: 305-585-7085; E-mail:[email protected] received 9 November 2000; Accepted for publication 7December 2000.Reprinted with permission fromJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Volume 12, No. 3, March 2001Copyright ©2001 by Futura Publishing Company, Inc., Armonk, NY 10504- 0418369250,000 to 400,000 or more.4 - 8This  gure of 300,000deaths accounts for an average o f 1 to 2 deaths per 1,0 00adults over the age o f 35 per year and represents 50% ofall heart-related deaths.8 , 9Althoug h the 50% proportionseems to hold up from a number of sources of data, theestimate of 300,000 SCDs per year is a derived  gure,based on an assumption of 600 ,000 cardiovascul ar deathsper year in the mid-1970s. Although much has changedin the population sub strate and interv entional capabilitiesin cardiovascular diseases d uring the past 25 years, theestimates that formed the basi s for the 300,000 SCDsannually have remained unchalle nged.An example of how changing clinical and epidemio-logic patterns can in  uence SCD risk witho ut beingimmediate ly apparent is shown in Figure 1. The decreasein age-adjusted risk of coronary heart disease death fromthe 1940s to 1995 (Fig. 1A) has been ap plauded as astatement of medical and pu blic health progress.1 0Dur-ing the same pe riod of time, there was a marked reduc-tion in earl y mortality from acute myocardial infarction,initiall y th ought to be related to the devel opment of th ecoronary care unit and its effect on electrical and, to amore limited extent, mechanical deaths, and recently bymore advanced therapies1 1 , 1 2(Fig. 1B). The interact ionbetween these two sources of data is complex. Theage-adjust ed risk curve expresses the fact that deathsfrom cardiovascular disease are occurring at older ages;it does no t inherently state that the prevalence of heartdisease or abs olute numbers of death have changed. Inaddition , the short-term acute my ocardial infarct ion mor-tality experience infers the establishme nt of a populationof survivors who entered the pool of aging patients withcardiovasc ular disease. These factors combine with thegeneral growth of the o lder popul ation pool, because ofincreased birth rates during the middle part of the cen-tury. These several observations come together to sug-gest that, in an aging population with a lower short-termmorality rate and a shifting age-adjusted risk, there islikely a growing population of patients at risk for variouscardiovasc ular events.1 2The events include the develop-ment of heart failure and the risk of SCD. Finally,