Sudden Cardiac Death

  1. Overview
  2. Epidemiology and Risk Factors
  3. Cardiac Causes by Age Group
  4. Prodromal Symptoms and Warning Signs
  5. Diagnosis and Risk Stratification
  6. Primary Prevention
  7. Secondary Prevention
  8. Special Considerations
  9. Prognosis and Survivorship
  10. Key Research Papers
  11. Connections

Overview

Sudden cardiac death (SCD) is most widely defined as unexpected death that occurs within one hour of the start of symptoms when the death is witnessed, or within 24 hours of the person last being seen alive and well when it is unwitnessed (PubMed PMID: 20142817). SCD is not a single diagnosis — it is a mode of death, a final common pathway for a wide range of underlying heart diseases and electrical disturbances.

Two terms are often confused: sudden cardiac arrest (SCA) is the event — the abrupt loss of effective heart pumping. Sudden cardiac death is the outcome when resuscitation fails or is not attempted. Every SCD begins as an SCA, but not every SCA ends in death.

Estimates of how many SCDs occur in the United States each year vary with how cases are counted. Older retrospective, death-certificate-based estimates were 300,000 to 450,000 a year; reviews of community studies that used several sources to find cases put the figure at about 180,000 to 250,000 a year, and SCD now accounts for more than half of all coronary heart disease deaths (PubMed PMID: 20142817; PubMed PMID: 19026856).

In most cases SCD is thought to follow ventricular tachycardia that degenerates to ventricular fibrillation (VF) and then asystole. In one study of confirmed cardiac arrest in which a defibrillator was used within 3 minutes, the first recorded rhythm was VT or VF in 71% of people, asystole in 18% and pulseless electrical activity (PEA) in 11%; in Seattle, VF was the first rhythm in only 41% of arrests by the year 2000, after a long decline (PubMed PMID: 20142817). VT and VF are the rhythms a defibrillator can shock; PEA and asystole are not.

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Epidemiology and Risk Factors

Community studies that used several sources to identify cases found annual SCD rates of about 53 per 100,000 residents in Multnomah County, Oregon, about 100 per 100,000 among 20–75-year-olds in Maastricht, the Netherlands, and 40–50 per 100,000 in studies from China and Ireland (PubMed PMID: 20142817).

Sex: middle-aged men have about a fourfold higher risk of SCD than women of the same age, a difference that narrows with age (PubMed PMID: 20142817). In one autopsy series of SCD at ages 35–44, the cause stayed undetermined after detailed examination in 50% of women compared with 24% of men (PubMed PMID: 19026856).

Race and ethnicity: racial differences in SCD have not been well studied; death-certificate data suggest SCD is more common among Black Americans than among white and Hispanic Americans (PubMed PMID: 20142817).

Age: in adults, SCD risk rises with age and mirrors the incidence of coronary heart disease (PubMed PMID: 20142817).

Autopsy studies of adults with SCD have found severe coronary heart disease in about 80%, dilated or hypertrophic cardiomyopathy in 10–15%, and a structurally normal heart in 5–10% (PubMed PMID: 20142817). Most SCD does not occur in an easily identified high-risk group: in community data reviewed by Chugh and colleagues, almost half of people who died of SCD had normal left ventricular function, and about 20% more had only mildly or moderately reduced function (ejection fraction above 35% and below 50%) (PubMed PMID: 19026856). Factors the research links to higher risk include:

SCD and out-of-hospital cardiac arrest are also more common in areas of socioeconomic deprivation (PubMed PMID: 20142817). Because most SCD occurs in people who are not identified as individually high-risk, the Adabag review describes heart-disease surveillance and community-wide risk-factor reduction (for example, smoking cessation) as extremely important for reducing SCD (PubMed PMID: 20142817).

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Cardiac Causes by Age Group

The causes of SCD differ substantially between younger and older people.

Pediatric and Young Adults (<35 Years)

In a US registry of 1,866 young competitive athletes who died suddenly or survived cardiac arrest between 1980 and 2006, cardiovascular disease accounted for 56% of the deaths; the most common cardiovascular causes were hypertrophic cardiomyopathy (36%) and congenital coronary artery anomalies (17%). Commotio cordis accounted for 3% of the deaths and blunt trauma with structural damage for 22% (PubMed PMID: 19221222). In a population-wide study of SCD among all people aged 1–35 in Australia and New Zealand (not only athletes), the most common explained causes were coronary artery disease (24%) and inherited cardiomyopathies (16%), and 40% of deaths stayed unexplained after a full autopsy (PubMed PMID: 27332903). Causes described in this age group include:

Middle-Aged and Older Adults (>35 Years)

Coronary heart disease dominates: autopsy studies find severe coronary disease in about 80% of adults with SCD (PubMed PMID: 20142817). In the Australian and New Zealand study, coronary artery disease was already the most common finding at ages 31–35 (PubMed PMID: 27332903). Beyond coronary disease, causes include:

Special Populations

Athletes: in the US registry, 82% of the cardiovascular deaths occurred with physical exertion during competition or training, 54% were in high school students and 11% in females (PubMed PMID: 19221222). In the Veneto region of Italy, the fall in athlete SCD after screening began was mostly due to fewer deaths from cardiomyopathies (PubMed PMID: 17018804).

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Prodromal Symptoms and Warning Signs

SCD is not always without warning. In a population-based study of 839 people aged 35–65 with SCA in the northwestern United States (2002–2012), 51% had warning symptoms in the 4 weeks before the arrest (50% of men and 53% of women), mainly chest pain and shortness of breath. In 93% of those with symptoms, the symptoms recurred within the 24 hours before the arrest (PubMed PMID: 26720493).

Only 19% of the people with symptoms called emergency services before the arrest. Survival was 32.1% among those who called in response to symptoms, compared with 6.0% among those who did not; the authors noted possible recall and response bias (PubMed PMID: 26720493). The Adabag review describes symptoms that are often tolerated for prolonged periods (about 75 minutes), particularly at home (PubMed PMID: 20142817).

Symptoms described before cardiac arrest include:

These symptoms are also common in people who are not about to have an arrest. Syncope in a person with known structural heart disease, cardiomyopathy or a family history of SCD is one of the risk markers listed above; unexplained syncope, for example, is one of the seven factors in the HCM risk model (PubMed PMID: 24126876).

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Diagnosis and Risk Stratification

The evaluation of an SCA survivor — or of a person with high-risk features — aims to identify the underlying cause and to estimate the risk of a further event. These findings guide treatment decisions and family screening.

Core Diagnostic Workup

Electrophysiology Testing

Programmed electrical stimulation delivers timed electrical impulses during a catheter study to try to induce VT or VF. Inducible sustained VT was one of the markers in an older risk algorithm described in the Adabag review (PubMed PMID: 20142817); MADIT-II enrolled patients without requiring this testing (PubMed PMID: 11907286).

Ambulatory Monitoring

Holter monitors, event monitors and implantable loop recorders record the heart rhythm over hours to months to catch intermittent arrhythmias and match them to symptoms.

Laboratory Evaluation

Typical tests include electrolytes (potassium, magnesium), thyroid function, a toxicology screen, natriuretic peptides (BNP/NT-proBNP) and troponin. Higher BNP levels were associated with higher SCD risk in people with left ventricular dysfunction and heart failure, and among women in the Nurses' Health Study (PubMed PMID: 20142817).

Autopsy and Molecular Autopsy

When a young person dies suddenly, autopsy and genetic testing can find a cause that would otherwise be missed. In the Australian and New Zealand study of SCD at ages 1–35, 40% of deaths had no cause after a comprehensive autopsy with toxicology and histology. Genetic testing of at least 59 cardiac genes found a clinically relevant mutation in 27% (31 of 113) of these unexplained deaths, and an inherited heart disease was later diagnosed in 13% of the families (PubMed PMID: 27332903).

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Primary Prevention

Primary prevention of SCD means preventing a first event in someone who has not had a cardiac arrest. Approaches work at the population level and at the level of individuals at high risk.

Population-Wide Strategies

High-Risk Primary Prevention: ICD Implantation

Randomized trials have tested implantable cardioverter-defibrillators (ICDs) in people with reduced ejection fraction who have never had a cardiac arrest:

Wearable Cardioverter-Defibrillator (WCD)

A wearable cardioverter-defibrillator is an external defibrillator worn by the patient. The VEST trial randomized 2,302 patients with a recent heart attack and ejection fraction of 35% or less. The device did not significantly lower the primary outcome, arrhythmic death (1.6% vs 2.4%; relative risk 0.67, P=0.18). Death from any cause was lower in the device group (3.1% vs 4.9%; uncorrected P=0.04), a secondary finding. Participants wore the device a median of 18 hours a day, and 12 of the 48 who died in the device group were wearing it at the time (PubMed PMID: 30280654).

HCM-Specific Primary Prevention

The HCM Risk-SCD model, developed from 3,675 patients at six centres, estimates an individual's 5-year risk of SCD from seven factors: age, maximal left ventricular wall thickness, left atrial diameter, left ventricular outflow tract gradient, family history of SCD, non-sustained VT and unexplained syncope. The authors estimated that for every 16 ICDs implanted in patients with a 5-year risk of 4% or more, one patient could be saved from SCD at 5 years (PubMed PMID: 24126876).

Athlete Screening

Italy introduced nationwide systematic pre-participation screening of athletes in 1982. In the Veneto region, the annual incidence of sudden cardiovascular death in young competitive athletes fell by 89% (from 3.6 to 0.4 per 100,000 person-years between 1979–1980 and 2003–2004), while the rate in unscreened non-athletes did not change significantly; most of the decline came from fewer deaths from cardiomyopathies (PubMed PMID: 17018804). This was an observational study of trends, not a randomized trial. In the United States, a 2014 American Heart Association / American College of Cardiology scientific statement assessed the 12-lead ECG as a screening test in young people aged 12–25 (PubMed PMID: 25223981). The Seattle Criteria (2013) were written by an international expert group to help physicians tell normal ECG changes in athletes from abnormal findings that need further evaluation (PubMed PMID: 23303758).

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Secondary Prevention

Secondary prevention means preventing SCD in someone who has already survived a cardiac arrest or sustained ventricular arrhythmia.

ICD Implantation After SCA

Three randomized trials (AVID, CASH and CIDS) compared ICDs with amiodarone in survivors of VF or sustained VT. A pooled analysis of individual patient data found a 28% reduction in the relative risk of death with the ICD, due almost entirely to a 50% reduction in arrhythmic death; survival was extended by a mean of 4.4 months over 6 years. Patients with an ejection fraction of 35% or less benefited significantly more than those with better-preserved function (PubMed PMID: 11102258).

Management After ICD Implantation

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Special Considerations

Athlete SCD

SCD during organized sports is especially visible because the people affected are young and presumed healthy. In the US athlete registry, the absolute number of cardiovascular sudden deaths was relatively low — fewer than 100 a year — and 82% occurred with physical exertion during competition or training (PubMed PMID: 19221222).

Commotio Cordis

Commotio cordis is VF triggered by a blunt, non-penetrating blow to the chest in a heart without structural abnormalities. Of 128 confirmed cases in the US Commotio Cordis Registry (to 2001), 95% were male, the median age was 14, and 62% occurred during organized sports such as baseball, while 38% happened during daily routine or recreation; 28% of the athletes involved were wearing chest barriers (PubMed PMID: 11879111). In a swine model using a baseball-sized object, 9 of 10 impacts timed 30 to 15 milliseconds before the peak of the T wave produced VF, and impacts at other times in the cardiac cycle did not (PubMed PMID: 9632447).

Survival has improved over time: in the registry, 10% of cases survived in 1970–1993, 34% in 1994–2012 and 58% in the most recent 6 years. Survival was 40% when resuscitation began within 3 minutes compared with 5% when it began later, and on-site AED use was protective (PubMed PMID: 23107651).

Drug-Induced SCD

A number of drugs prolong the QTc interval and can precipitate torsades de pointes leading to VF. In community data, people with QT prolongation in the absence of QT-prolonging drugs or diabetes had a fivefold higher risk of SCD (PubMed PMID: 20142817).

Family Screening After SCD

When a young person dies suddenly without explanation, examining surviving relatives can uncover an inherited cause. In a Dutch study of 43 families with at least one unexplained sudden death at age 40 or younger, cardiological and genetic examination of relatives with resting and exercise ECG and echocardiography identified an inherited disease in 17 families (40%) — most often CPVT, long QT syndrome or Brugada syndrome — and found 151 previously unrecognized carriers (8.9 per family) (PubMed PMID: 15998675). In the Australian and New Zealand study, an inherited cardiovascular disease was diagnosed in 13% of families after an unexplained SCD (PubMed PMID: 27332903).

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Prognosis and Survivorship

Survival after cardiac arrest depends heavily on the speed of resuscitation. In the Resuscitation Outcomes Consortium study, overall survival to hospital discharge after out-of-hospital cardiac arrest was 7% (PubMed PMID: 20394876); the Adabag review describes overall survival of about 5% and reports that 95% of patients die after 10 minutes or longer without defibrillation (PubMed PMID: 20142817).

Neurological Outcomes After Resuscitation

In a single-centre study of patients who regained a circulation but died before discharge, withdrawal of care for neurological reasons was the reason for death in 73% after out-of-hospital arrest and 27% after in-hospital arrest (PubMed PMID: 30710595).

Two trials published in 2002 tested cooling after cardiac arrest. In a multicentre trial of patients resuscitated from VF, cooling to 32–34°C for 24 hours gave a favourable neurological outcome in 55% compared with 39% with normal temperature, and 6-month mortality of 41% compared with 55% (PubMed PMID: 11856793). In a second trial, of 77 comatose survivors of out-of-hospital arrest, cooling to 33°C for 12 hours was followed by a good outcome in 49% compared with 26% (PubMed PMID: 11856794). The later TTM trial of 950 unconscious adults compared two target temperatures, both intended to prevent fever, and found no benefit of 33°C over 36°C for mortality or neurological outcome (PubMed PMID: 24237006).

Long-Term Prognosis

In Olmsted County, Minnesota, 5-year survival among people who had an out-of-hospital VF arrest and survived to hospital discharge was 79%, equal to that of matched people without cardiac arrest (PubMed PMID: 20142817). Ongoing issues reported for survivors include recurrent ventricular arrhythmias needing ICD therapy, inappropriate ICD shocks, progression of the underlying heart disease, heart failure and psychological effects in survivors and families.

Survivor Support Resources

Patient organizations offer support, education and advocacy for SCA survivors, families of people who died suddenly, and people with inherited arrhythmia syndromes.

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Key Research Papers

  1. Adabag AS, Luepker RV, Roger VL, Gersh BJ. Sudden cardiac death: epidemiology and risk factors. Nat Rev Cardiol. 2010;7(4):216-225. — PubMed PMID: 20142817
  2. Chugh SS, Reinier K, Teodorescu C, et al. Epidemiology of sudden cardiac death: clinical and research implications. Prog Cardiovasc Dis. 2008;51(3):213-228. — PubMed PMID: 19026856
  3. Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006. Circulation. 2009;119(8):1085-1092. — PubMed PMID: 19221222
  4. Bagnall RD, Weintraub RG, Ingles J, et al. A prospective study of sudden cardiac death among children and young adults. N Engl J Med. 2016;374(25):2441-2452. — PubMed PMID: 27332903
  5. Marijon E, Uy-Evanado A, Dumas F, et al. Warning symptoms are associated with survival from sudden cardiac arrest. Ann Intern Med. 2016;164(1):23-29. — PubMed PMID: 26720493
  6. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction (MADIT-II). N Engl J Med. 2002;346(12):877-883. — PubMed PMID: 11907286
  7. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure (SCD-HeFT). N Engl J Med. 2005;352(3):225-237. — PubMed PMID: 15659722
  8. Køber L, Thune JJ, Nielsen JC, et al. Defibrillator implantation in patients with nonischemic systolic heart failure (DANISH). N Engl J Med. 2016;375(13):1221-1230. — PubMed PMID: 27571011
  9. Olgin JE, Pletcher MJ, Vittinghoff E, et al. Wearable cardioverter-defibrillator after myocardial infarction (VEST). N Engl J Med. 2018;379(13):1205-1215. — PubMed PMID: 30280654
  10. O'Mahony C, Jichi F, Pavlou M, et al. A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD). Eur Heart J. 2014;35(30):2010-2020. — PubMed PMID: 24126876
  11. Connolly SJ, Hallstrom AP, Cappato R, et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials: AVID, CASH and CIDS studies. Eur Heart J. 2000;21(24):2071-2078. — PubMed PMID: 11102258
  12. Moss AJ, Schuger C, Beck CA, et al. Reduction in inappropriate therapy and mortality through ICD programming (MADIT-RIT). N Engl J Med. 2012;367(24):2275-2283. — PubMed PMID: 23131066
  13. Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA. 2006;296(13):1593-1601. — PubMed PMID: 17018804
  14. Maron BJ, Friedman RA, Kligfield P, et al. Assessment of the 12-lead ECG as a screening test for detection of cardiovascular disease in healthy general populations of young people (12-25 years of age): a scientific statement from the American Heart Association and the American College of Cardiology. Circulation. 2014;130(15):1303-1334. — PubMed PMID: 25223981
  15. Drezner JA, Ackerman MJ, Anderson J, et al. Electrocardiographic interpretation in athletes: the 'Seattle criteria'. Br J Sports Med. 2013;47(3):122-124. — PubMed PMID: 23303758
  16. Maron BJ, Gohman TE, Kyle SB, Estes NA 3rd, Link MS. Clinical profile and spectrum of commotio cordis. JAMA. 2002;287(9):1142-1146. — PubMed PMID: 11879111
  17. Link MS, Wang PJ, Pandian NG, et al. An experimental model of sudden death due to low-energy chest-wall impact (commotio cordis). N Engl J Med. 1998;338(25):1805-1811. — PubMed PMID: 9632447
  18. Maron BJ, Haas TS, Ahluwalia A, et al. Increasing survival rate from commotio cordis. Heart Rhythm. 2013;10(2):219-223. — PubMed PMID: 23107651
  19. Priori SG, Napolitano C, Tiso N, et al. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation. 2001;103(2):196-200. — PubMed PMID: 11208676
  20. Tan HL, Hofman N, van Langen IM, et al. Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives. Circulation. 2005;112(2):207-213. — PubMed PMID: 15998675
  21. Hasselqvist-Ax I, Riva G, Herlitz J, et al. Early cardiopulmonary resuscitation in out-of-hospital cardiac arrest. N Engl J Med. 2015;372(24):2307-2315. — PubMed PMID: 26061835
  22. Weisfeldt ML, Sitlani CM, Ornato JP, et al. Survival after application of automatic external defibrillators before arrival of the emergency medical system: evaluation in the Resuscitation Outcomes Consortium population of 21 million. J Am Coll Cardiol. 2010;55(16):1713-1720. — PubMed PMID: 20394876
  23. Witten L, Gardner R, Holmberg MJ, et al. Reasons for death in patients successfully resuscitated from out-of-hospital and in-hospital cardiac arrest. Resuscitation. 2019;136:93-99. — PubMed PMID: 30710595
  24. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549-556. — PubMed PMID: 11856793
  25. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557-563. — PubMed PMID: 11856794
  26. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest (TTM). N Engl J Med. 2013;369(23):2197-2206. — PubMed PMID: 24237006

PubMed Topic Searches

  1. PubMed: Sudden cardiac death prevention and ICD therapy
  2. PubMed: SCD epidemiology and risk factor identification
  3. PubMed: SCD in young athletes and sports
  4. PubMed: HCM and SCD risk stratification
  5. PubMed: OHCA survival bystander CPR outcomes
  6. PubMed: Inherited channelopathies and sudden death

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Connections

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