Dr. Alisher Agzamov MD PhD
The treatment of sudden cardiac death (SCD) consists of acute
resuscitation followed, in survivors, by attempted long-term prevention of
recurrence by pharmacologic and nonpharmacologic means. However, despite
advances in treatment of heart disease, the outcome of patients experiencing
SCD remains poor. In a study of 515 patients with out-of-hospital sudden death
from 1991 to 1994, cardiac resuscitation was attempted in 51 percent and 13.5
percent were subsequently discharged alive from the hospital, resulting in an
overall survival rate of 6.2 percent [1].
Furthermore, a relatively good quality of life can be achieved in the patient who survives. In one study of 827 resuscitated patients, 20 percent survived to hospital discharge and 12 percent were alive at six months [2]. Most of the survivors (75 percent) were independent in daily life.
This card will review the issues related to acute therapy, including the guidelines for cardiopulmonary resuscitation. Issues related to prevention of recurrent sudden cardiac death are discussed separately. (See "Pharmacologic therapy in survivors of sudden cardiac death" and see "Nonpharmacologic therapy in survivors of sudden cardiac death: Role of surgery and radiofrequency ablation").
ARRHYTHMIC ETIOLOGY AND OUTCOME OF RESUSCITATION — There is an association between the arrhythmic mechanism for SCD and the outcome of resuscitation. (See "Pathophysiology and etiology of sudden cardiac death" for a review of the arrhythmic mechanisms).
• When the initial rhythm is asystole, the likelihood of successful resuscitation is low and, when performed out of hospital, very few of these patients (less than 10 percent) survive to hospitalization [3]. Furthermore, a number of studies have found that virtually none of these patients survive to be discharged from the hospital [4].
• The outcome is much better when the initial rhythm is a sustained ventricular tachyarrhythmia. Approximately 25 percent of patients with ventricular fibrillation (VF) survive to be discharged; in the majority of these patients an acute myocardial infarction is the underlying mechanism [5]. In comparison, survival of those with hemodynamically unstable ventricular tachycardia (VT) is 65 to 70 percent [6]. The prognosis may be better in patients found in monomorphic VT because of the potential of some systemic perfusion during this more organized arrhythmia. In addition, patients with VT tend to have a lower incidence of a remote myocardial infarction and a higher ejection fraction when compared to those with VF [7].
The poor outcome in patients with bradycardia due to a very slow idioventricular rhythm or asystole probably reflects the prolonged duration of the cardiac arrest, usually more than four minutes, and the presence of severe and irreversible myocardial damage. The myocardial damage and extinction of electrical activity result from severe tissue hypoxemia, a metabolic acidosis and hyperkalemia which develop rapidly. Ultimately there is also irreversible damage of other organs.
Patients who have SCD due to electrical-mechanical dissociation (pulseless electrical activity) also have a poor outcome. In one study of 150 such patients, 35 patients (23 percent) were resuscitated and survived to hospital admission [8]. However, 19 patients died in hospital and only 16 (11 percent) were discharged.
End-tidal carbon dioxide levels have excellent correlation with very low cardiac outputs when measured after at least 10 minutes CPR, and may provide prognostic information during a cardiopulmonary resuscitation. One study reported that an end-tidal carbon dioxide level
10
mmHg, measured after 20 minutes of standard cardiopulmonary resuscitation
(CPR), identified individuals who did not survive to hospitalization discharge
with a sensitivity and specificity of 100 percent [8]. The
end-tidal carbon dioxide level did not discriminate between patients who
survived to hospital discharge or those who died in hospital.
OUTCOME OF NONCARDIAC SUDDEN DEATH — While the most frequent mechanism for sudden death is a ventricular tachyarrhythmia due to underlying heart disease, one study reported that noncardiac causes accounted for 34 percent of cases [9]. (See "Pathophysiology and etiology of sudden cardiac death"). Trauma, nontraumatic bleeding, intoxication, near drowning, and pulmonary embolism were the most common noncardiac etiologies of sudden death in this study, and 40 percent of patients were successfully resuscitated and hospitalized. However, only 11 percent were discharged from the hospital and only 6 were neurologically intact or had mild disability.
FACTORS RELATED TO THE OUTCOME OF RESUSCITATION — Sudden cardiac death is a catastrophic event. Ventricular fibrillation in the human heart does not terminate spontaneously and survival is therefore dependent upon prompt cardiopulmonary resuscitation. The only effective way to reestablish organized electrical activity and myocardial contraction is prompt electrical defibrillation (show figure 1).
It has been estimated that ischemic changes begin with the onset of the ventricular arrhythmia due to the absence of tissue perfusion. Organ damage becomes irreversible after approximately four minutes of VF and cessation of cardiac output [10]. As a result, the longer the duration of the cardiac arrest, the lower the likelihood of resuscitation or survival even if initial resuscitation is successful (see below).
The Seattle Heart Watch program has reported on the outcome of patients resuscitated at the scene by a bystander trained in cardiopulmonary resuscitation (CPR) compared with CPR initiated by emergency medical personnel [11]. While there was no difference in the percentage of patients resuscitated at the scene and admitted alive to the hospital (67 versus 61 percent), the percentage discharged alive was significantly higher among those with bystander-initiated CPR (43 versus 22 percent, p< 0.001) (show figure 2).
The most important reason for the improvement in survival was that earlier CPR and prompt defibrillation were associated with less damage to the central nervous system. More patients with bystander-initiated CPR were conscious at the time of hospital admission (50 versus 9 percent), and more regained consciousness by the end of hospitalization (81 versus 52 percent) [11].
These observations were confirmed by a second larger study which analyzed data from 1872 patients with a witnessed cardiac arrest due to ventricular fibrillation [12]. Overall, 31 percent of patients survived to hospital discharge. Lower age, bystander-initiated CPR, and shorter intervals between collapse, CPR, and defibrillation were significantly associated with survival. Another study found that performing CPR for at least 90 seconds prior to defibrillation improves survival, especially in patients for whom the initial response interval was over four minutes (27 versus 17 percent without prior CPR) [13].
Optimizing the emergency medical system within a community and reducing the response interval to within eight minutes can improve the survival to hospital discharge. This was observed in one study of 6331 patients who had an out-of-hospital cardiac arrest; the overall survival to hospital discharge improved by 33 percent after the response time was shortened (5.2 versus 3.9 percent), representing an additional 21 lives saved [14].
Causes of in-hospital mortality — The cause of death in hospital is most often noncardiac, usually being due to anoxic encephalopathy or to respiratory complications from long-term respirator dependence [15]. Only about 10 percent of patients die from recurrent arrhythmia, while approximately 30 percent die from a low cardiac output or cardiogenic shock [16]. Recurrence of severe arrhythmia in the hospital is associated with a poor outcome [17].
Risk factors for mortality — Despite the efforts of emergency personnel, resuscitation is successful in only one-third of patients, and only about 10 percent of all patients are ultimately discharged from the hospital [18,19,20,21,22]. In addition to later onset of CPR, there are a number of other factors that are associated with a poor outcome with CPR [5,23,24,25,26,27]:
• Absence of any vital signs
• Sepsis
• Cerebrovascular accident with severe neurologic deficit
• Cancer or Alzheimer's disease
• History of more than two chronic diseases
• A history of cardiac disease
• An initial rhythm of asystole or pulseless electrical activity (electromechanical dissociation)
• CPR lasting more five minutes
There are also several poor prognostic features in survivors of CPR:
• Persistent coma after CPR
• Hypotension, pneumonia, renal failure after CPR
• Need for intubation or pressors
• Class 3 or 4 congestive heart failure
• Older age
In order to identify those patients who will survive and recover neurologically, one study reviewed the records of 127 patients who underwent CPR [28]. A cardiac arrest score was developed, based upon the time to return of spontaneous circulation (<25 minutes=1,
25
minutes=0), the initial systolic blood pressure (90
mmHg=1, <90 mmHg=0), and initial neurologic status (alert, arousable,
spontaneous movement=1; unresponsive or comatose=0) [28]. Scores
of 0, 1, 2, and 3 predicted in-hospital mortality rates of 90, 71, 42, and 18
percent, respectively and neurologic recovery in 3, 17, 57, and 89 percent,
respectively.
ACUTE THERAPY FOR THE SUDDEN CARDIAC DEATH VICTIM — As noted above, ventricular fibrillation in the human heart does not spontaneously terminate; as a result, survival is dependent upon prompt successful defibrillation and CPR and the reestablishment of organized electrical activity with a stable sinus or supraventricular rhythm.
The only effective approach for terminating VF is defibrillation using 200 to 400 J of energy delivered transthoracically in a nonsynchronized fashion [29]. Biphasic waveforms, truncated rectilinear exponential waveform with an initial positive phase followed by a phase of opposite polarity or a quasi-sinusoidal biphasic waveform, have been investigated for transthoracic applications and found to be superior to monophasic exponential waveforms (show figure 3) [30,31]. One study demonstrated fewer postshock arrhythmias and less contractile dysfunction when using biphasic compared with monophasic waveforms [32]. (See "Basic principles and technique of cardioversion and defibrillation").
While defibrillation is life-saving, direct current shock to the heart delivered transthoracically or epicardially can generate free radicals which may be in part responsible for defibrillation injury [33]. The generation of free radicals is related to the peak energy of an individual shock, not the cumulative energy delivered.
The initial success of defibrillation depends upon the duration of the arrhythmia and promptness of defibrillation (show figure 4) [34]:
• When VF has been present for seconds to a few minutes and the fibrillatory waves are coarse, the success rate is high.
• As VF continues for a longer period of time, the fibrillatory waves become finer, possibly due to depletion of myocardial epinephrine stores, and the ability to terminate the arrhythmia is reduced [35].
• When VF continues for more than four minutes, there is irreversible damage to the central nervous system and other organs which will impact on survival even if there is initially successful defibrillation [36].
Guidelines for CPR have been established by the American Heart Association and are depicted in the accompanying figures (show figure 5A-5D) [37].
Intravenous amiodarone — VF or VT that persists despite defibrillation or which recurs promptly after successful defibrillation is not uncommon. The current guidelines recommend therapy with an intravenous antiarrhythmic drug, although benefit from such therapy is not certain. The ARREST trial randomized 504 patients with a cardiac arrest due to VF or pulseless VT who were not resuscitated after at least three defibrillation shocks to intravenous amiodarone (300 mg) or placebo [38]. Although the mean time to resuscitation and number of shocks delivered were the same, survival to hospitalization was greater in the amiodarone group (44 versus 34 percent, p = 0.03), especially in patients who had a transient return of pulse during defibrillation and then received amiodarone (64 versus 41 percent) (show figure 6). Time to therapy with the study drug was an independent predictor of survival to hospital; faster treatment was associated with a better outcome (show figure 7). However, the incidence of hypotension (59 versus 48 percent) and bradycardia requiring therapy (41 versus 25 percent) was greater with amiodarone therapy compared to placebo. More than 50 percent of patients who survived to discharge had no neurological impairment. (See "Clinical use of amiodarone" and see "Major side effects of amiodarone").
Intravenous amiodarone is also effective for acute suppression of life-threatening, hemodynamically significant ventricular tachyarrhythmias that recur despite therapy with other agents. Amiodarone has been reported to prevent recurrence of sustained spontaneous VT or VF in more than 50 percent of patients, and has been approved for the acute treatment and prevention of ventricular fibrillation and hemodynamically destabilizing VT that is refractory to other agents [39,40]. Patients who respond to intravenous amiodarone and are discharged on oral drug have a good outcome. As an example, in one study of 107 patients surviving hospitalization, the one-year survival was 80 percent [41].
Left ventricular dysfunction — After cardiac resuscitation there is a variable period of global left ventricular systolic and diastolic dysfunction, perhaps representing myocardial "stunning" as a result of prolonged hypoxemia [42]. In an animal model, left ventricular dysfunction begins 15 minutes after resuscitation, peaks at five hours, and recovers by 48 hours [43]. In this model, dobutamine begun within 15 minutes of resuscitation prevents the development of left ventricular dysfunction resulting from prolonged cardiac arrest and cardiopulmonary resuscitation [44].
LONG-TERM OUTCOME OF SUDDEN DEATH SURVIVORS — The long-term mortality of the sudden death survivor is high, regardless of the therapy received [45,46]. In one series of 227 survivors, the mortality rate was 20 percent at one year and 50 percent at three years [46].
Similar considerations apply to patients with life-threatening ventricular arrhythmia in the absence of sudden death. This issue was addressed in the AVID registry, which enrolled 4219 patients with life-threatening ventricular arrhythmia or syncope felt to be due to a ventricular arrhythmia [47]. After an average follow-up of 17 months, the morality was high regardless of the arrhythmic mechanism or therapy received (eg, implantable device, antiarrhythmic drug, both, or neither) and regardless of whether the arrhythmia was ventricular fibrillation, ventricular tachycardia with syncope, symptomatic ventricular tachycardia, asymptomatic ventricular tachycardia, a ventricular tachyarrhythmia due to a transient/correctable cause, or unexplained syncope (12.3 to 21.2 percent).
Interestingly the mortality is higher for patients with an in-hospital presentation of life threatening ventricular arrhythmia not due to a reversible cause compared to those presenting with out-of-hospital arrhythmia, perhaps because in-hospital patients are sicker with more concomitant diseases [48]. The one and two year adjusted mortality rates were 15 and 21 percent versus 8.4 and 14 percent for out-of-hospital arrhythmia; the adjusted long-term relative risk for in-hospital versus out-of-hospital presentation was 1.6.
Furthermore, a relatively good quality of life can be achieved in the patient who survives. In one study of 827 resuscitated patients, 20 percent survived to hospital discharge and 12 percent were alive at six months [2]. Most of the survivors (75 percent) were independent in daily life.
This card will review the issues related to acute therapy, including the guidelines for cardiopulmonary resuscitation. Issues related to prevention of recurrent sudden cardiac death are discussed separately. (See "Pharmacologic therapy in survivors of sudden cardiac death" and see "Nonpharmacologic therapy in survivors of sudden cardiac death: Role of surgery and radiofrequency ablation").
ARRHYTHMIC ETIOLOGY AND OUTCOME OF RESUSCITATION — There is an association between the arrhythmic mechanism for SCD and the outcome of resuscitation. (See "Pathophysiology and etiology of sudden cardiac death" for a review of the arrhythmic mechanisms).
• When the initial rhythm is asystole, the likelihood of successful resuscitation is low and, when performed out of hospital, very few of these patients (less than 10 percent) survive to hospitalization [3]. Furthermore, a number of studies have found that virtually none of these patients survive to be discharged from the hospital [4].
• The outcome is much better when the initial rhythm is a sustained ventricular tachyarrhythmia. Approximately 25 percent of patients with ventricular fibrillation (VF) survive to be discharged; in the majority of these patients an acute myocardial infarction is the underlying mechanism [5]. In comparison, survival of those with hemodynamically unstable ventricular tachycardia (VT) is 65 to 70 percent [6]. The prognosis may be better in patients found in monomorphic VT because of the potential of some systemic perfusion during this more organized arrhythmia. In addition, patients with VT tend to have a lower incidence of a remote myocardial infarction and a higher ejection fraction when compared to those with VF [7].
The poor outcome in patients with bradycardia due to a very slow idioventricular rhythm or asystole probably reflects the prolonged duration of the cardiac arrest, usually more than four minutes, and the presence of severe and irreversible myocardial damage. The myocardial damage and extinction of electrical activity result from severe tissue hypoxemia, a metabolic acidosis and hyperkalemia which develop rapidly. Ultimately there is also irreversible damage of other organs.
Patients who have SCD due to electrical-mechanical dissociation (pulseless electrical activity) also have a poor outcome. In one study of 150 such patients, 35 patients (23 percent) were resuscitated and survived to hospital admission [8]. However, 19 patients died in hospital and only 16 (11 percent) were discharged.
End-tidal carbon dioxide levels have excellent correlation with very low cardiac outputs when measured after at least 10 minutes CPR, and may provide prognostic information during a cardiopulmonary resuscitation. One study reported that an end-tidal carbon dioxide level
10
mmHg, measured after 20 minutes of standard cardiopulmonary resuscitation
(CPR), identified individuals who did not survive to hospitalization discharge
with a sensitivity and specificity of 100 percent [8]. The
end-tidal carbon dioxide level did not discriminate between patients who
survived to hospital discharge or those who died in hospital.OUTCOME OF NONCARDIAC SUDDEN DEATH — While the most frequent mechanism for sudden death is a ventricular tachyarrhythmia due to underlying heart disease, one study reported that noncardiac causes accounted for 34 percent of cases [9]. (See "Pathophysiology and etiology of sudden cardiac death"). Trauma, nontraumatic bleeding, intoxication, near drowning, and pulmonary embolism were the most common noncardiac etiologies of sudden death in this study, and 40 percent of patients were successfully resuscitated and hospitalized. However, only 11 percent were discharged from the hospital and only 6 were neurologically intact or had mild disability.
FACTORS RELATED TO THE OUTCOME OF RESUSCITATION — Sudden cardiac death is a catastrophic event. Ventricular fibrillation in the human heart does not terminate spontaneously and survival is therefore dependent upon prompt cardiopulmonary resuscitation. The only effective way to reestablish organized electrical activity and myocardial contraction is prompt electrical defibrillation (show figure 1).
It has been estimated that ischemic changes begin with the onset of the ventricular arrhythmia due to the absence of tissue perfusion. Organ damage becomes irreversible after approximately four minutes of VF and cessation of cardiac output [10]. As a result, the longer the duration of the cardiac arrest, the lower the likelihood of resuscitation or survival even if initial resuscitation is successful (see below).
The Seattle Heart Watch program has reported on the outcome of patients resuscitated at the scene by a bystander trained in cardiopulmonary resuscitation (CPR) compared with CPR initiated by emergency medical personnel [11]. While there was no difference in the percentage of patients resuscitated at the scene and admitted alive to the hospital (67 versus 61 percent), the percentage discharged alive was significantly higher among those with bystander-initiated CPR (43 versus 22 percent, p< 0.001) (show figure 2).
The most important reason for the improvement in survival was that earlier CPR and prompt defibrillation were associated with less damage to the central nervous system. More patients with bystander-initiated CPR were conscious at the time of hospital admission (50 versus 9 percent), and more regained consciousness by the end of hospitalization (81 versus 52 percent) [11].
These observations were confirmed by a second larger study which analyzed data from 1872 patients with a witnessed cardiac arrest due to ventricular fibrillation [12]. Overall, 31 percent of patients survived to hospital discharge. Lower age, bystander-initiated CPR, and shorter intervals between collapse, CPR, and defibrillation were significantly associated with survival. Another study found that performing CPR for at least 90 seconds prior to defibrillation improves survival, especially in patients for whom the initial response interval was over four minutes (27 versus 17 percent without prior CPR) [13].
Optimizing the emergency medical system within a community and reducing the response interval to within eight minutes can improve the survival to hospital discharge. This was observed in one study of 6331 patients who had an out-of-hospital cardiac arrest; the overall survival to hospital discharge improved by 33 percent after the response time was shortened (5.2 versus 3.9 percent), representing an additional 21 lives saved [14].
Causes of in-hospital mortality — The cause of death in hospital is most often noncardiac, usually being due to anoxic encephalopathy or to respiratory complications from long-term respirator dependence [15]. Only about 10 percent of patients die from recurrent arrhythmia, while approximately 30 percent die from a low cardiac output or cardiogenic shock [16]. Recurrence of severe arrhythmia in the hospital is associated with a poor outcome [17].
Risk factors for mortality — Despite the efforts of emergency personnel, resuscitation is successful in only one-third of patients, and only about 10 percent of all patients are ultimately discharged from the hospital [18,19,20,21,22]. In addition to later onset of CPR, there are a number of other factors that are associated with a poor outcome with CPR [5,23,24,25,26,27]:
• Absence of any vital signs
• Sepsis
• Cerebrovascular accident with severe neurologic deficit
• Cancer or Alzheimer's disease
• History of more than two chronic diseases
• A history of cardiac disease
• An initial rhythm of asystole or pulseless electrical activity (electromechanical dissociation)
• CPR lasting more five minutes
There are also several poor prognostic features in survivors of CPR:
• Persistent coma after CPR
• Hypotension, pneumonia, renal failure after CPR
• Need for intubation or pressors
• Class 3 or 4 congestive heart failure
• Older age
In order to identify those patients who will survive and recover neurologically, one study reviewed the records of 127 patients who underwent CPR [28]. A cardiac arrest score was developed, based upon the time to return of spontaneous circulation (<25 minutes=1,
25
minutes=0), the initial systolic blood pressure (90
mmHg=1, <90 mmHg=0), and initial neurologic status (alert, arousable,
spontaneous movement=1; unresponsive or comatose=0) [28]. Scores
of 0, 1, 2, and 3 predicted in-hospital mortality rates of 90, 71, 42, and 18
percent, respectively and neurologic recovery in 3, 17, 57, and 89 percent,
respectively.ACUTE THERAPY FOR THE SUDDEN CARDIAC DEATH VICTIM — As noted above, ventricular fibrillation in the human heart does not spontaneously terminate; as a result, survival is dependent upon prompt successful defibrillation and CPR and the reestablishment of organized electrical activity with a stable sinus or supraventricular rhythm.
The only effective approach for terminating VF is defibrillation using 200 to 400 J of energy delivered transthoracically in a nonsynchronized fashion [29]. Biphasic waveforms, truncated rectilinear exponential waveform with an initial positive phase followed by a phase of opposite polarity or a quasi-sinusoidal biphasic waveform, have been investigated for transthoracic applications and found to be superior to monophasic exponential waveforms (show figure 3) [30,31]. One study demonstrated fewer postshock arrhythmias and less contractile dysfunction when using biphasic compared with monophasic waveforms [32]. (See "Basic principles and technique of cardioversion and defibrillation").
While defibrillation is life-saving, direct current shock to the heart delivered transthoracically or epicardially can generate free radicals which may be in part responsible for defibrillation injury [33]. The generation of free radicals is related to the peak energy of an individual shock, not the cumulative energy delivered.
The initial success of defibrillation depends upon the duration of the arrhythmia and promptness of defibrillation (show figure 4) [34]:
• When VF has been present for seconds to a few minutes and the fibrillatory waves are coarse, the success rate is high.
• As VF continues for a longer period of time, the fibrillatory waves become finer, possibly due to depletion of myocardial epinephrine stores, and the ability to terminate the arrhythmia is reduced [35].
• When VF continues for more than four minutes, there is irreversible damage to the central nervous system and other organs which will impact on survival even if there is initially successful defibrillation [36].
Guidelines for CPR have been established by the American Heart Association and are depicted in the accompanying figures (show figure 5A-5D) [37].
Intravenous amiodarone — VF or VT that persists despite defibrillation or which recurs promptly after successful defibrillation is not uncommon. The current guidelines recommend therapy with an intravenous antiarrhythmic drug, although benefit from such therapy is not certain. The ARREST trial randomized 504 patients with a cardiac arrest due to VF or pulseless VT who were not resuscitated after at least three defibrillation shocks to intravenous amiodarone (300 mg) or placebo [38]. Although the mean time to resuscitation and number of shocks delivered were the same, survival to hospitalization was greater in the amiodarone group (44 versus 34 percent, p = 0.03), especially in patients who had a transient return of pulse during defibrillation and then received amiodarone (64 versus 41 percent) (show figure 6). Time to therapy with the study drug was an independent predictor of survival to hospital; faster treatment was associated with a better outcome (show figure 7). However, the incidence of hypotension (59 versus 48 percent) and bradycardia requiring therapy (41 versus 25 percent) was greater with amiodarone therapy compared to placebo. More than 50 percent of patients who survived to discharge had no neurological impairment. (See "Clinical use of amiodarone" and see "Major side effects of amiodarone").
Intravenous amiodarone is also effective for acute suppression of life-threatening, hemodynamically significant ventricular tachyarrhythmias that recur despite therapy with other agents. Amiodarone has been reported to prevent recurrence of sustained spontaneous VT or VF in more than 50 percent of patients, and has been approved for the acute treatment and prevention of ventricular fibrillation and hemodynamically destabilizing VT that is refractory to other agents [39,40]. Patients who respond to intravenous amiodarone and are discharged on oral drug have a good outcome. As an example, in one study of 107 patients surviving hospitalization, the one-year survival was 80 percent [41].
Left ventricular dysfunction — After cardiac resuscitation there is a variable period of global left ventricular systolic and diastolic dysfunction, perhaps representing myocardial "stunning" as a result of prolonged hypoxemia [42]. In an animal model, left ventricular dysfunction begins 15 minutes after resuscitation, peaks at five hours, and recovers by 48 hours [43]. In this model, dobutamine begun within 15 minutes of resuscitation prevents the development of left ventricular dysfunction resulting from prolonged cardiac arrest and cardiopulmonary resuscitation [44].
LONG-TERM OUTCOME OF SUDDEN DEATH SURVIVORS — The long-term mortality of the sudden death survivor is high, regardless of the therapy received [45,46]. In one series of 227 survivors, the mortality rate was 20 percent at one year and 50 percent at three years [46].
Similar considerations apply to patients with life-threatening ventricular arrhythmia in the absence of sudden death. This issue was addressed in the AVID registry, which enrolled 4219 patients with life-threatening ventricular arrhythmia or syncope felt to be due to a ventricular arrhythmia [47]. After an average follow-up of 17 months, the morality was high regardless of the arrhythmic mechanism or therapy received (eg, implantable device, antiarrhythmic drug, both, or neither) and regardless of whether the arrhythmia was ventricular fibrillation, ventricular tachycardia with syncope, symptomatic ventricular tachycardia, asymptomatic ventricular tachycardia, a ventricular tachyarrhythmia due to a transient/correctable cause, or unexplained syncope (12.3 to 21.2 percent).
Interestingly the mortality is higher for patients with an in-hospital presentation of life threatening ventricular arrhythmia not due to a reversible cause compared to those presenting with out-of-hospital arrhythmia, perhaps because in-hospital patients are sicker with more concomitant diseases [48]. The one and two year adjusted mortality rates were 15 and 21 percent versus 8.4 and 14 percent for out-of-hospital arrhythmia; the adjusted long-term relative risk for in-hospital versus out-of-hospital presentation was 1.6.
1. de
Vreede-Swagemakers, JJ, Gorgels, AP, Dubois-Arbouw, WI, et al. Out-of-hospital
cardiac arrest in the 1990s: A population-based study in the Maastricht area on
incidence, characteristics and survival. J Am Coll Cardiol 1997; 30:1500.
2. de Vos, R, de Haes, HCJM, Koster, RW, et al. Quality of life after cardiopulmonary resuscitation. Arch Intern Med 1999; 159:249.
3. Weaver, WD, Cobb, LA, Hallstrom, AP, et al. Factors influencing survival after out-of- hospital cardiac arrest. J Am Coll Cardiol 1986; 7:752
4. Gray, WA, Capone, RJ, Most, AS. Unsuccessful emergency resuscitation: Are continued efforts in the emergency department justified? N Engl J Med 1991; 325:1393
5. de Vreede-Swagemakers, JJM, Gorgels, APM, Dubois-Arbouz, WI, et al. Circumstances and causes of out-of-hospital cardiac arrest in sudden death survivors. Heart 1998; 79:356.
6. Goldstein, S, Landis, JR, Leighton, R, et al. Characteristics of the resuscitated out-of-hospital cardiac arrest victim with coronary heart disease. Circulation 1981; 64:977.
7. Adhar, GC, Larson, LW, et al. Sustained ventricular arrhythmias: difference between survivors of cardiac arrest and patients with recurrent ventricular tachycardia. J Am Coll Cardiol 1988; 12:159.
8. Levine, RL, Wayne, MA, Miller, CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med 1997; 337:301.
9. Kuisma, M, Alaspaa, A. Out-of-hospital cardiac arrest of non-cardiac origin. Epidemiology and outcome. Eur Heart J 1997; 18:1122.
10. Olson, DW, LaRochelle, J, Fark, D, et al. EMT-defibrillation: The Wisconsin experience. Ann Emerg Med 1989; 18:806.
11. Thompson, RG, Hallstrom, AP, Cobb, LA. Bystander-initiated cardiopulmonary resuscitation in the management of ventricular fibrillation. Ann Intern Med 1979; 90:737.
12. Valenzuela, TD, Roe, DJ, Cretin, S, et al. Estimating effectiveness of cardiac arrest interventions. A logistic regression survival model. Circulation 1997; 96:3308.
13. Stiell, IG, Wells, GA, Field, BJ, et al, for the OPALS Study Group. Improved out-of-hospital cardiac arrest survival through the inexpensive optimization of an existing defibrillation program: OPALS study phase II. JAMA 1999; 281:1175.
14. Cobb, LA, Fahrenbruch, CE, Walsh, TR, et al. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. JAMA 1999; 281:1182.
15. Myerburg, RJ, Conde, CA, Sung, RJ, et al. Clinical, electrophysiologic, and hemodynamic profile of patients resuscitated from prehospital cardiac arrest. Am J Med 1980; 68:568.
16. Myerburg, RJ, Conde, CA, Sung, RJ, et al. Clinical, electrophysiologic, and hemodynamic profile of patients resuscitated from prehospital cardiac arrest. Am J Med 1980; 68:568.
17. Myerburg, RJ, Kessler, KM, Zaman, L, et al. Survivors of prehospital cardiac arrest. JAMA 1982; 247:1485.
18. Liberthson, RR, Nagel, EL, Hirschman, JC, Nussenfeld, SR. Prehospital ventricular defibrillation. Prognosis and follow-up course. N Engl J Med 1974; 291:317.
19. Taffet, GE, Teasdale, TA, Luchi, RJ. In-hospital cardiopulmonary resuscitation. JAMA 1988; 260:2069.
20. Bedell, SE, Delbanco, TL, Cook, EF, Epstein, FH. Survival after cardiopulmonary resuscitation in the hospital. N Engl J Med 1983; 309:569.
21. Murphy, DJ, Murray, AM, Robinson, BE, et al. Outcomes of cardiopulmonary resuscitation in the elderly. Ann Intern Med 1989; 111:199.
22. Ritter, G, Wolfe, RA, Goldstein, S, et al. The effect of bystander CPR on survival in out-of-hospital cardiac arrest victims. Am Heart J 1985; 110:932.
23. Greene, HL. Sudden arrhythmic cardiac death-mechanism, resuscitation and classification: The Seattle perspective. Am J Cardiol 1990; 65:43.
24. Roberts, D, Landolfo, G, Light, HB, et al. Early predictors of mortality for hospitalized patients suffering cardiopulmonary arrest. Chest 1990; 97:413.
25. Tortolani, AJ, Resucci, DA, Rosati, RJ, et al. In-hospital cardiopulmonary: patient arrest and resuscitation factors associated with survival. Resuscitation 1990; 20:115.
26. Marwick, TH, Case, CC, Siskind, V, et al. Prediction of survival from resuscitation: A prognostic index derived from multivariate logistic model analysis. Resuscitation 1991; 22:122.
27. Burns, R, Graney, MJ, Nichols, LO. Prediction of in-hospital cardiopulmonary arrest outcome. Arch Intern Med 1989; 149:1318.
28. Thompson, RJ, McCullough, PA, Kahn, JK, et al. Prediction of death and neurologic outcome in the emergency department in out-of-hospital cardiac arrest survivors. Am J Cardiol 1998; 81:17.
29. Chen, PS, Wolf, PD, Ideker, RE. Mechanism of cardiac defibrillation: A different point of view. Circulation 1991; 84:913.
30. Schuder, JC, McDaniel, WC, Stoeckle, H. Defibrillation of 100 kg calves with asymmetrical, bidirectional, rectangular pulses. Cardiovasc Res 1984; 18:419.
31. Walcott, GP, Melnick, SB, Chapman, FW, et al. Relative efficacy of monophasic and biphasic waveforms for transthoracic defibrillation after short and long durations of ventricular fibrillation. Circulation 1998; 98:2210.
32. Jones, JL, Jones, RE. Improved defibrillator waveform safety factor with biphasic waveforms. Am J Physiol 1983; 245:H60.
33. Caterine, MR, Spencer, KT, Pagan-Carlo, LA, et al. Direct current shocks to the heart generate free radicals: An electron paramagnetic resonance study. J Am Coll Cardiol 1996; 28:1598.
34. Winkle, RA, Mead, RH, Ruder, MA, et al. Effect of duration of ventricular fibrillation on defibrillation efficacy in humans. Circulation 1990; 81:1477.
35. Niemann, JT, Cairns, CB, Sharma, J, et al. Treatment of prolonged ventricular fibrillation: Immediate countershock versus high-dose epinephrine and CPR preceding countershock. Circulation 1992; 85:281.
36. Baum, RS, Alvarez, H, Cobb, LA. Survival after resuscitation from out-of-hospital ventricular fibrillation. Circulation 1974; 50:1231.
37. American Heart Association. Currents in Emergency Cardiac Care. American Heart Association, Dallas, 1992.
38. Kudenchuk, PJ, Cobb, LA, Copass, MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med 1999; 341:871.
39. Scheinman, MM, Levine, JH, Cannom, DS, et al. Dose-ranging study of intravenous amiodarone in patients with life-threatening ventricular tachyarrhythmias. Circulation 1995; 92:3264.
40. Kowey, PR, Levine, JH, Herre, JM, et al. Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. The Intravenous Amiodarone Multicenter Investigators Group. Circulation 1995; 92:3255.
41. Fogel, RI, Herre, JM, Kopelman, HA, et al. Long-term follow-up of patients requiring intravenous amiodarone to suppress hemodynamically destabilizing ventricular arrhythmias. Am Heart J 2000; 139:690.
42. Gazmuri, RJ, Weil, MH, Bisera, J, et al. Myocardial dysfunction after successful resuscitation from cardiac arrest. Crit Care Med 1996; 24:992.
43. Kern, KB, Hilwig, RW, Rhee, KH, et al. Myocardial dysfunction following resuscitation from cardiac arrest: an example of global myocardial stunning. J Am Coll Cardiol 1996; 28:232.
44. Kern, KB, Hilwig, RW, Berg, RA, et al. Postresuscitation left ventricular systolic and diastolic dysfunction. Treatment with dobutamine. Circulation 1997; 95:2610.
45. Schaffer, WA, Cobb, LA. Recurrent ventricular fibrillation and modes of death in survivors of out-of-hospital ventricular fibrillation. N Engl J Med 1975; 293:259.
46. Goldstein, S, Landis, JR, Leighton, R, et al. Predictive survival models for resuscitated victims of out-of-hospital cardiac arrest with coronary heart disease. Circulation 1985; 71:873.
47. Anderson, JL, Hallstrom, AP, Epstein, AE, et al, and the AVID Investigators. Design and results of the Antiarrhythmics vs Implantable Defibrillator (AVID) registry. Circulation 1999; 99:1692.
48. Epstein, AE, Powell, J, Yao, Q, et al. In-hospital versus out-of-hospital presentation of life-threatening ventricular arrhythmias predicts survival: results from the AVID Registry. Antiarrhythmics Versus Implantable Defibrillators. J Am Coll Cardiol 1999; 34:1111.
2. de Vos, R, de Haes, HCJM, Koster, RW, et al. Quality of life after cardiopulmonary resuscitation. Arch Intern Med 1999; 159:249.
3. Weaver, WD, Cobb, LA, Hallstrom, AP, et al. Factors influencing survival after out-of- hospital cardiac arrest. J Am Coll Cardiol 1986; 7:752
4. Gray, WA, Capone, RJ, Most, AS. Unsuccessful emergency resuscitation: Are continued efforts in the emergency department justified? N Engl J Med 1991; 325:1393
5. de Vreede-Swagemakers, JJM, Gorgels, APM, Dubois-Arbouz, WI, et al. Circumstances and causes of out-of-hospital cardiac arrest in sudden death survivors. Heart 1998; 79:356.
6. Goldstein, S, Landis, JR, Leighton, R, et al. Characteristics of the resuscitated out-of-hospital cardiac arrest victim with coronary heart disease. Circulation 1981; 64:977.
7. Adhar, GC, Larson, LW, et al. Sustained ventricular arrhythmias: difference between survivors of cardiac arrest and patients with recurrent ventricular tachycardia. J Am Coll Cardiol 1988; 12:159.
8. Levine, RL, Wayne, MA, Miller, CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med 1997; 337:301.
9. Kuisma, M, Alaspaa, A. Out-of-hospital cardiac arrest of non-cardiac origin. Epidemiology and outcome. Eur Heart J 1997; 18:1122.
10. Olson, DW, LaRochelle, J, Fark, D, et al. EMT-defibrillation: The Wisconsin experience. Ann Emerg Med 1989; 18:806.
11. Thompson, RG, Hallstrom, AP, Cobb, LA. Bystander-initiated cardiopulmonary resuscitation in the management of ventricular fibrillation. Ann Intern Med 1979; 90:737.
12. Valenzuela, TD, Roe, DJ, Cretin, S, et al. Estimating effectiveness of cardiac arrest interventions. A logistic regression survival model. Circulation 1997; 96:3308.
13. Stiell, IG, Wells, GA, Field, BJ, et al, for the OPALS Study Group. Improved out-of-hospital cardiac arrest survival through the inexpensive optimization of an existing defibrillation program: OPALS study phase II. JAMA 1999; 281:1175.
14. Cobb, LA, Fahrenbruch, CE, Walsh, TR, et al. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. JAMA 1999; 281:1182.
15. Myerburg, RJ, Conde, CA, Sung, RJ, et al. Clinical, electrophysiologic, and hemodynamic profile of patients resuscitated from prehospital cardiac arrest. Am J Med 1980; 68:568.
16. Myerburg, RJ, Conde, CA, Sung, RJ, et al. Clinical, electrophysiologic, and hemodynamic profile of patients resuscitated from prehospital cardiac arrest. Am J Med 1980; 68:568.
17. Myerburg, RJ, Kessler, KM, Zaman, L, et al. Survivors of prehospital cardiac arrest. JAMA 1982; 247:1485.
18. Liberthson, RR, Nagel, EL, Hirschman, JC, Nussenfeld, SR. Prehospital ventricular defibrillation. Prognosis and follow-up course. N Engl J Med 1974; 291:317.
19. Taffet, GE, Teasdale, TA, Luchi, RJ. In-hospital cardiopulmonary resuscitation. JAMA 1988; 260:2069.
20. Bedell, SE, Delbanco, TL, Cook, EF, Epstein, FH. Survival after cardiopulmonary resuscitation in the hospital. N Engl J Med 1983; 309:569.
21. Murphy, DJ, Murray, AM, Robinson, BE, et al. Outcomes of cardiopulmonary resuscitation in the elderly. Ann Intern Med 1989; 111:199.
22. Ritter, G, Wolfe, RA, Goldstein, S, et al. The effect of bystander CPR on survival in out-of-hospital cardiac arrest victims. Am Heart J 1985; 110:932.
23. Greene, HL. Sudden arrhythmic cardiac death-mechanism, resuscitation and classification: The Seattle perspective. Am J Cardiol 1990; 65:43.
24. Roberts, D, Landolfo, G, Light, HB, et al. Early predictors of mortality for hospitalized patients suffering cardiopulmonary arrest. Chest 1990; 97:413.
25. Tortolani, AJ, Resucci, DA, Rosati, RJ, et al. In-hospital cardiopulmonary: patient arrest and resuscitation factors associated with survival. Resuscitation 1990; 20:115.
26. Marwick, TH, Case, CC, Siskind, V, et al. Prediction of survival from resuscitation: A prognostic index derived from multivariate logistic model analysis. Resuscitation 1991; 22:122.
27. Burns, R, Graney, MJ, Nichols, LO. Prediction of in-hospital cardiopulmonary arrest outcome. Arch Intern Med 1989; 149:1318.
28. Thompson, RJ, McCullough, PA, Kahn, JK, et al. Prediction of death and neurologic outcome in the emergency department in out-of-hospital cardiac arrest survivors. Am J Cardiol 1998; 81:17.
29. Chen, PS, Wolf, PD, Ideker, RE. Mechanism of cardiac defibrillation: A different point of view. Circulation 1991; 84:913.
30. Schuder, JC, McDaniel, WC, Stoeckle, H. Defibrillation of 100 kg calves with asymmetrical, bidirectional, rectangular pulses. Cardiovasc Res 1984; 18:419.
31. Walcott, GP, Melnick, SB, Chapman, FW, et al. Relative efficacy of monophasic and biphasic waveforms for transthoracic defibrillation after short and long durations of ventricular fibrillation. Circulation 1998; 98:2210.
32. Jones, JL, Jones, RE. Improved defibrillator waveform safety factor with biphasic waveforms. Am J Physiol 1983; 245:H60.
33. Caterine, MR, Spencer, KT, Pagan-Carlo, LA, et al. Direct current shocks to the heart generate free radicals: An electron paramagnetic resonance study. J Am Coll Cardiol 1996; 28:1598.
34. Winkle, RA, Mead, RH, Ruder, MA, et al. Effect of duration of ventricular fibrillation on defibrillation efficacy in humans. Circulation 1990; 81:1477.
35. Niemann, JT, Cairns, CB, Sharma, J, et al. Treatment of prolonged ventricular fibrillation: Immediate countershock versus high-dose epinephrine and CPR preceding countershock. Circulation 1992; 85:281.
36. Baum, RS, Alvarez, H, Cobb, LA. Survival after resuscitation from out-of-hospital ventricular fibrillation. Circulation 1974; 50:1231.
37. American Heart Association. Currents in Emergency Cardiac Care. American Heart Association, Dallas, 1992.
38. Kudenchuk, PJ, Cobb, LA, Copass, MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med 1999; 341:871.
39. Scheinman, MM, Levine, JH, Cannom, DS, et al. Dose-ranging study of intravenous amiodarone in patients with life-threatening ventricular tachyarrhythmias. Circulation 1995; 92:3264.
40. Kowey, PR, Levine, JH, Herre, JM, et al. Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. The Intravenous Amiodarone Multicenter Investigators Group. Circulation 1995; 92:3255.
41. Fogel, RI, Herre, JM, Kopelman, HA, et al. Long-term follow-up of patients requiring intravenous amiodarone to suppress hemodynamically destabilizing ventricular arrhythmias. Am Heart J 2000; 139:690.
42. Gazmuri, RJ, Weil, MH, Bisera, J, et al. Myocardial dysfunction after successful resuscitation from cardiac arrest. Crit Care Med 1996; 24:992.
43. Kern, KB, Hilwig, RW, Rhee, KH, et al. Myocardial dysfunction following resuscitation from cardiac arrest: an example of global myocardial stunning. J Am Coll Cardiol 1996; 28:232.
44. Kern, KB, Hilwig, RW, Berg, RA, et al. Postresuscitation left ventricular systolic and diastolic dysfunction. Treatment with dobutamine. Circulation 1997; 95:2610.
45. Schaffer, WA, Cobb, LA. Recurrent ventricular fibrillation and modes of death in survivors of out-of-hospital ventricular fibrillation. N Engl J Med 1975; 293:259.
46. Goldstein, S, Landis, JR, Leighton, R, et al. Predictive survival models for resuscitated victims of out-of-hospital cardiac arrest with coronary heart disease. Circulation 1985; 71:873.
47. Anderson, JL, Hallstrom, AP, Epstein, AE, et al, and the AVID Investigators. Design and results of the Antiarrhythmics vs Implantable Defibrillator (AVID) registry. Circulation 1999; 99:1692.
48. Epstein, AE, Powell, J, Yao, Q, et al. In-hospital versus out-of-hospital presentation of life-threatening ventricular arrhythmias predicts survival: results from the AVID Registry. Antiarrhythmics Versus Implantable Defibrillators. J Am Coll Cardiol 1999; 34:1111.
