327: Cardiovascular Collapse, Cardiac Arrest, and Sudden Cardiac Death

Sudden cardiac death (SCD) is defined as natural death due to cardiac causes in a person who may or may not have previously recognized heart disease but in whom the time and mode of death are unexpected. The term “sudden,” in the context of SCD, is defined for most clinical and epidemiologic purposes as 1 h or less between a change in clinical status heralding the onset of the terminal clinical event and the cardiac arrest itself. One exception is unwitnessed deaths, in which pathologists may expand the temporal definition to 24 h after the victim was last seen to be alive and stable.

Another exception is the variable interval between cardiac arrest and biological death that results from community-based interventions, following which victims may remain biologically alive for days or even weeks after a cardiac arrest that has resulted in irreversible central nervous system damage. Confusion in terms can be avoided by adhering strictly to definitions of cardiovascular collapse, cardiac arrest, and death (Table 327-1). Although cardiac arrest is often potentially reversible by appropriate and timely interventions, death is biologically, legally, and literally an absolute and irreversible event. Biological death may be delayed by interventions, but the relevant pathophysiologic event remains the sudden and unexpected cardiac arrest. Accordingly, for statistical purposes, deaths that occur during hospitalization or within 30 days after resuscitated cardiac arrest are counted as sudden deaths.

The majority of natural deaths are caused by cardiac disorders. However, it is common for underlying heart diseases—often far advanced—to go unrecognized before the fatal event. As a result, up to two-thirds of all SCDs occur as the first clinical expression of previously undiagnosed disease or in patients with known heart disease, the extent of which suggests low individual risk. The magnitude of sudden cardiac death as a public health problem is highlighted by the estimate that ~50% of all cardiac deaths are sudden and unexpected, accounting for a total SCD burden estimated to range from <200,000 to >450,000 deaths each year in the United States. SCD is a direct consequence of cardiac arrest, which may be reversible if addressed promptly. Because resuscitation techniques and emergency rescue systems are available to respond to victims of out-of-hospital cardiac arrest, which was uniformly fatal in the past, understanding the SCD problem has practical clinical importance.

CLINICAL DEFINITION OF FORMS OF CARDIOVASCULAR COLLAPSE

Cardiovascular collapse is a general term connoting loss of sufficient cerebral blood flow to maintain consciousness due to acute dysfunction of the heart and/or peripheral vasculature. It may be caused by vasodepressor syncope (vasovagal syncope, postural hypotension with syncope, neurocardiogenic syncope; Chap. 27), a transient severe bradycardia, or cardiac arrest. The latter is distinguished from the transient forms of cardiovascular collapse in that it usually requires an active intervention to restore spontaneous blood flow. In contrast, vasodepressor syncope and other primary bradyarrhythmic syncopal events are transient and non-life-threatening, with spontaneous return of consciousness.

In the past, the most common electrical mechanism for cardiac arrest was ventricular fibrillation (VF) or pulseless sustained ventricular tachycardia (PVT). These were the initial rhythms recorded in 60–80% of cardiac arrests, with VF being the far more common of the two. Severe persistent bradyarrhythmias, asystole, and pulseless electrical activity (PEA; organized electrical activity, unusually slow, without mechanical response, formerly called electromechanical dissociation [EMD]) caused another 20–30%. Currently, asystole has emerged as the most common mechanism recorded at initial contact (45–50% of cases). PEA accounts for 20–25%, and VF is now present on initial contact in 25–35%. Undoubtedly, a significant proportion of the asystole cases began as VF and deteriorated to asystole because of long response times, but there are data suggesting an absolute reduction in VF as well. Acute low cardiac output states, having a precipitous onset, also may present clinically as a cardiac arrest. These hemodynamic causes include massive acute pulmonary emboli, internal blood loss from a ruptured aortic aneurysm, intense anaphylaxis, and cardiac rupture with tamponade after myocardial infarction (MI).

Clinical, epidemiologic, and pathologic studies have provided information on the underlying structural substrates in victims of SCD and identified subgroups at high risk for SCD. In addition, studies of clinical physiology have begun to identify transient functional factors that may convert a long-standing underlying structural abnormality from a stable to an unstable state, leading to the onset of cardiac arrest (Table 327-2).

Cardiac disorders constitute the most common causes of sudden natural death. After an initial peak incidence of sudden death between birth and 6 months of age (sudden infant death syndrome [SIDS]), the incidence of sudden death declines sharply and remains low through childhood and adolescence. Among adolescents and young adults, the incidence of SCD is approximately 1 per 100,000 population per year. The incidence begins to increase in adults over age 30 years, reaching a second peak in the age range of 45–75 years, when it approximates 1–2 per 1000 per year among the unselected adult population. Increasing age within this range is associated with increasing risk for sudden cardiac death (Fig. 327-1A). From 1 to 13 years of age, only one of five sudden natural deaths is due to cardiac causes. Between 14 and 21 years of age, the proportion increases to 30%, and it rises to 88% in the middle-aged and elderly.

Young and middle-aged men and women have different susceptibilities to SCD, but the sex differences decrease and ultimately disappear with advancing age. The difference in risk for SCD parallels the differences in age-related risks for other manifestations of coronary heart disease (CHD) between men and women. As the gender gap for manifestations of CHD closes in the sixth to eighth decades of life, the excess risk of SCD in males progressively narrows. Despite the lower incidence among younger women, coronary risk factors such as cigarette smoking, diabetes, hyperlipidemia, and hypertension are highly influential, and SCD remains an important clinical and epidemiologic problem. The incidence of SCD among the African-American population appears to be higher than it is among the white population; the reasons remain uncertain.

Genetic factors contribute to the risk of acquiring CHD, and a genetic basis for its expression as SCD is being explored. A genetic hypothesis for at least part of the SCD risk is supported by data suggesting a familial predisposition to SCD as a specific form of expression of CHD. A parental history of SCD as a first cardiac event increases the probability that an acute coronary event in the offspring will express similarly. In a number of less common syndromes, such as hypertrophic cardiomyopathy, congenital long QT interval syndromes, right ventricular dysplasia, and the syndrome of right bundle branch block and nonischemic ST-segment elevations (Brugada syndrome), and other more rare syndromes, there is a specific inherited risk of ventricular arrhythmias and SCD (Chap. 277).

The etiologic structural substrates and functional factors contributing to expression of the SCD syndrome are listed in Table 327-2. Worldwide, and especially in Western cultures, coronary atherosclerotic heart disease is the most common structural abnormality associated with SCD in middle-aged and older adults. Up to 80% of all SCDs in the United States are due to the consequences of coronary atherosclerosis. The nonischemic cardiomyopathies (dilated and hypertrophic, collectively; Chap. 273e) account for another 10–15% of SCDs, and all the remaining diverse etiologies cause only 5–10% of all SCDs. The inherited arrhythmia syndromes (see above and Table 327-2) are proportionally more common causes in adolescents and young adults. For some of these syndromes, such as hypertrophic cardiomyopathy (Chap. 287), the risk of SCD increases significantly after the onset of puberty.

Transient ischemia in a previously scarred or hypertrophied heart, hemodynamic and fluid and electrolyte disturbances, fluctuations in autonomic nervous system activity, and transient electrophysiologic changes caused by drugs or other chemicals (e.g., proarrhythmia) have all been implicated as mechanisms responsible for the transition from electrophysiologic stability to instability. In addition, reperfusion of ischemic myocardium may cause transient electrophysiologic instability and arrhythmias.

PATHOLOGY

Data from postmortem examinations of SCD victims parallel the clinical observations on the prevalence of CHD as the major structural etiologic factor. More than 80% of SCD victims have pathologic findings of CHD. The pathologic description often includes a combination of long-standing, extensive atherosclerosis of the epicardial coronary arteries and unstable coronary artery lesions, which include various permutations of eroded, fissured, or ruptured plaques; platelet aggregates; hemorrhage; and/or thrombosis. As many as 70–75% of males who die suddenly have preexisting healed MIs, whereas only 20–30% have recent acute MIs, despite the prevalence of unstable plaques and thrombi. The latter suggests transient ischemia as the mechanism of onset. Regional or global left ventricular (LV) hypertrophy often coexists with prior MIs.

SCD accounts for approximately one-half the total number of cardiovascular deaths. As shown in Fig. 327-1B, the very-high-risk subgroups consist of more focused populations at higher risk of cardiac arrest or SCD, with better individual prediction, but the representation of such subgroups within the overall population burden of SCD is small. This is indicated by the absolute number of events (“events per year”), in contrast to the percentage per year in the subgroup. To achieve a major population impact, effective prevention of underlying diseases and the development of new epidemiologic and clinical probes that will allow better individual risk prediction by identifying specific high-risk subgroups within the large general populations are needed.

Strategies for predicting and preventing SCD are classified as primary and secondary. Primary prevention refers to the attempt to identify individual patients at specific risk for SCD and institute preventive strategies. Secondary prevention refers to measures taken to prevent recurrent cardiac arrest or death in individuals who have survived a prior cardiac arrest.

The effectiveness of the prevention strategies currently used depends on the magnitude of risk among the various population subgroups. Because the annual incidence of SCD among the unselected adult population is limited to approximately 1 per 1000 population per year (Fig. 327-1) and ~50% of all SCDs due to coronary artery disease occur as the first clinical manifestation of the disease (Fig. 327-2A), the only currently practical strategies are profiling for risk of developing CHD and risk factor control (Fig. 327-2B). The most powerful long-term risk factors include age, cigarette smoking, elevated serum cholesterol, diabetes mellitus, elevated blood pressure, LV hypertrophy, and nonspecific electrocardiographic abnormalities. Markers of inflammation (e.g., levels of C-reactive protein) that may predict plaque destabilization have been added to risk classifications. The presence of multiple risk factors progressively increases incidence, but not sufficiently or specifically enough to warrant therapies targeted to potentially fatal arrhythmias (Fig. 327-1A). However, recent studies suggesting familial clustering of SCD associated with a first acute coronary syndrome offer hope that genetic markers for specific risk may be forthcoming.

After coronary artery disease has been identified in a patient, additional strategies for risk profiling become available (Fig. 327-2B), but the majority of SCDs occur among the large unselected groups rather than in the specific high-risk subgroups that become evident among populations with established disease (compare events per year with percentage per year in Fig. 327-1B). After a major cardiovascular event, such as acute MI, recent onset of heart failure, or survival after out-of-hospital cardiac arrest, the highest risk of death occurs during the initial 6–18 months after the event and then plateaus toward the baseline risk associated with the extent of underlying disease. However, many of the early deaths are nonsudden, diluting the potential benefit of strategies targeted specifically to SCD. Thus, although post-MI beta blocker therapy has an identifiable benefit for both early SCD and nonsudden mortality risk, a total mortality benefit for implantable cardioverter-defibrillator (ICD) therapy early after MI has not been observed.

Among patients in the acute, convalescent, and chronic phases of MI (Chap. 295), subgroups at high absolute risk of SCD can be identified. During the acute phase, the potential risk of cardiac arrest from onset through the first 48 h used to be as high as 15%, but is now reported in the range of 2.3–4.4% because of early patient awareness of the significance of symptoms and the availability of emergency revascularization strategies. Those who survive acute-phase VF are not at continuing risk for recurrent cardiac arrest indexed to that event. During the convalescent phase after MI (3 days to ~6 weeks), an episode of sustained ventricular tachycardia (VT) or VF, which is usually associated with a large infarct, predicts a natural history mortality risk of >25% at 12 months. At least one-half of the deaths are sudden. Aggressive intervention techniques may reduce this incidence.

During the chronic phase after MI, the longer-term risk for total mortality and SCD mortality is predicted by a number of factors (Fig. 327-2B). The most important for both SCD and nonsudden death is the extent of myocardial damage sustained as a result of the acute MI. This is measured by the magnitude of reduction of the ejection fraction (EF) and/or the occurrence of heart failure. Various studies have demonstrated that ventricular arrhythmias identified by ambulatory monitoring contribute significantly to this risk, especially in patients with an EF <40%. In addition, inducibility of VT or VF during electrophysiologic testing of patients who have ambient ventricular arrhythmias (premature ventricular contractions [PVCs] and nonsustained VT) and an EF <35% is a strong predictor of SCD risk. Patients in this subgroup are now considered candidates for ICDs (see below). Risk falls off sharply with EFs >35% and the absence of ambient arrhythmias after MI, and conversely is high with EFs <30% even without the ambient arrhythmia markers.

The cardiomyopathies (dilated and hypertrophic, Chap. 287) are the second most common category of diseases associated with risk of SCD (Table 327-2). Some risk factors have been identified, largely related to extent of disease, presence of heart failure, documented ventricular arrhythmias, and syncope thought to be due to arrhythmias. The less common causes of SCD include valvular heart disease (primarily aortic) and inflammatory and infiltrative disorders of the myocardium. The latter include viral myocarditis, sarcoidosis, and amyloidosis.

Among adolescents and young adults, rare inherited disorders such as hypertrophic cardiomyopathy, the long QT interval syndromes, right ventricular dysplasia, and the Brugada syndrome have received attention as important causes of SCD, as has acute myocarditis and other less common acquired diseases. Among the subgroup of young competitive athletes, the incidence of SCD may be higher than it is for the general adolescent and young adult population, perhaps up to 1 in 75,000–100,000. Hypertrophic cardiomyopathy (Chap. 287) is the most common cause in the United States.

Secondary prevention strategies should be applied to survivors of cardiac arrest that was not associated with an acute MI or other controllable transient risk factors, such as certain drug exposures and correctable electrolyte imbalances. Multivessel coronary artery disease and dilated cardiomyopathy, especially with markedly reduced left ventricular EF, predict a high risk of recurrence of cardiac arrest or SCD and are indications for specific interventions, such as ICDs (see below). The occurrence of otherwise unexplained syncope or documented life-threatening arrhythmias in patients with long QT syndromes or right ventricular dysplasia are also associated with increased risk of SCD.

PRODROME, ONSET, ARREST, DEATH

SCD may be presaged by days to months of increasing angina, dyspnea, palpitations, easy fatigability, and other nonspecific complaints. However, these prodromal symptoms are generally predictive of any major cardiac event; they are not specific for predicting SCD.

The onset of the clinical transition, leading to cardiac arrest, is defined as an acute change in cardiovascular status preceding cardiac arrest by up to 1 h. When the onset is instantaneous or abrupt, the probability that the arrest is cardiac in origin is >95%. Continuous electrocardiogram (ECG) recordings fortuitously obtained at the onset of a cardiac arrest commonly demonstrate a tendency for the heart rate to increase and for advanced grades of PVCs to evolve during the minutes or hours before the event.

The probability of achieving successful resuscitation from cardiac arrest is related to the interval from onset of loss of circulation to return of spontaneous circulation (ROSC), the setting in which the event occurs, the mechanism (VF, VT, PEA, asystole), and the clinical status of the patient before the cardiac arrest. ROSC and survival rates as a result of defibrillation decrease almost linearly from the first minute to 10 min. After 4-5 min, survival rates are no better than 25–30% in out-of-hospital settings without bystander cardiopulmonary resuscitation (CPR). Those settings in which it is possible to institute prompt CPR followed by prompt defibrillation provide a better chance of a successful outcome. The outcome in intensive care units and other in-hospital environments is heavily influenced by the patient’s preceding clinical status. The immediate outcome is good for cardiac arrest occurring in the intensive care unit in the presence of an acute cardiac event or transient metabolic disturbance, but survival among patients with far-advanced chronic cardiac disease or advanced noncardiac diseases (e.g., renal failure, pneumonia, sepsis, diabetes, cancer) is low and not much better in the in-hospital setting. Survival rates after unexpected cardiac arrest in unmonitored areas in a hospital do not differ from witnessed out-of-hospital arrests. Since implementation of community response systems, survival from out-of-hospital cardiac arrest has improved, although it still remains low, under most circumstances. Survival probabilities in public sites exceed those in the home environment, where the majority of cardiac arrests occur.

The success rate for initial resuscitation and survival to hospital discharge after an out-of-hospital cardiac arrest depends heavily on the mechanism of the event. When the mechanism is pulseless VT, the outcome is best; VF is the next most successful; and asystole and PEA, now the most common mechanisms, generate dismal outcome statistics. Advanced age also adversely influences the chances of successful resuscitation.

The probability of progression to biologic death is a function of the mechanism of cardiac arrest and the length of the delay before interventions. VF without CPR within the first 4–6 min has a poor outcome even if defibrillation is successful because of secondary brain damage; the prompt interposition of bystander CPR (basic life support; see below) improves outcome at any point along the time scale, especially when followed by early successful defibrillation. However, there are few survivors among patients who had no life support activities for the first 8 min after onset. Evaluations of deployment of automatic external defibrillators (AEDs) in communities (e.g., police vehicles, large buildings, airports, and stadiums) are beginning to generate encouraging data, but the data for home deployment has been have been less impressive.

Death during the hospitalization after a successfully resuscitated cardiac arrest relates closely to the severity of central nervous system injury. Anoxic encephalopathy and infections subsequent to prolonged respirator dependence account for 60% of the deaths. Another 30% occur as a consequence of low cardiac output states that fail to respond to interventions. Recurrent arrhythmias are the least common cause of death, accounting for only 10% of in-hospital deaths.

In the setting of acute MI (Chap. 295), it is important to distinguish between primary and secondary cardiac arrests. Primary cardiac arrests are those that occur in the absence of hemodynamic instability, and secondary cardiac arrests are those that occur in patients in whom abnormal hemodynamics dominate the clinical picture before cardiac arrest. The success rate for immediate resuscitation in primary cardiac arrest during acute MI in a monitored setting should exceed 90%. In contrast, as many as 70% of patients with secondary cardiac arrest succumb immediately or during the same hospitalization.

TREATMENT

Post-MI patients with EFs <35% and other markers of risk such as ambient ventricular arrhythmias, inducible ventricular tachyarrhythmias in the electrophysiology laboratory, and a history of heart failure are considered candidates for ICDs 40 days or more after the MI. Total mortality benefits in the range of a 20–35% reduction over 2–5 years have been observed in a series of clinical trials. One study suggested that an EF <30% was a sufficient marker of risk to indicate ICD benefit, and another demonstrated benefit for patients with Functional Class 2 or 3 heart failure and EFs ≤35%, regardless of etiology (ischemic or nonischemic) or the presence of ambient or induced arrhythmias (Chaps. 277 and 279). For patients with newly diagnosed heart failure and an EF <35%, the required delay between diagnosis and institution of medical therapy, and subsequent implantation of an ICD, is 90 days. In general, there appears to be a gradient of increasing ICD benefit with EFs ranging lower than the threshold indications. However, patients with very low EFs (e.g., <20%) may receive less benefit.

Decision making for primary prevention in disorders other than coronary artery disease and dilated cardiomyopathy is generally driven by observational data and judgment based on clinical observations. Controlled clinical trials providing evidence-based indicators for ICDs are lacking for these smaller population subgroups. In general, for the rare disorders listed above, indicators of arrhythmic risk such as syncope, documented ventricular tachyarrhythmias, aborted cardiac arrest, or a family history of premature SCD in some conditions, and a number of other clinical or ECG markers, may be used as indicators for ICDs.