Causes
Ischemic heart disease
Cardiac arrest due to ventricular arrhythmias may be due to post-MI remodeling of the heart with scar formation and interstitial fibrosis (intramyocardial collagen deposition) or to acute MI/ischemia. A chronic infarct scar can serve as the focus for reentrant ventricular tachyarrhythmias. This can occur shortly after the infarct or years later. Interestingly, post-MI remodeling and ischemic cardiomyopathy may be associated with increased interstitial fibrosis even in noninfarcted areas of the heart.[12] Interstitial fibrosis can provide anatomical block similar to a scar. Fibroblasts and myocytes shown to be coupled through gap junctions and fibroblasts can reduce repolarization reserve of myocytes. In addition to post-MI remodeling, many other structural heart diseases associated with SCD (eg, dilated cardiomyopathy, hypertrophic cardiomyopathy, and aortic stenosis) are also associated with increased myocardial fibrosis.[13, 14, 15]
Many studies support the relationship of symptomatic and asymptomatic ischemia as a factor for risk of SCD. Patients resuscitated from out-of-hospital cardiac arrest represent a group of patients with increased recurrence of cardiac arrest and have been shown to express an increased incidence of silent ST-segment depression. Experiments inducing myocardial ischemia in animal models have a strong relationship with the development of VF. However, in patients with prior myocardial infarction and scarring, ventricular arrhythmias, especially VT, do not require an acute ischemic trigger.
In postmortem studies of people who have died from SCD, extensive atherosclerosis is a common pathologic finding. In survivors of cardiac arrest, coronary heart disease with vessels showing greater than 75% stenosis is observed in 40-86% of patients, depending on the age and sex of the population studied. Autopsy studies show similar results; in one study of 169 hearts, approximately 61% of patients died of SCD, and more than 75% stenosis in 3 or 4 vessels and similar severe lesions were present in at least 2 vessels in another 15% of cases. No single coronary artery lesion is associated with an increased risk for SCD. Despite these findings, only approximately 20% of SCD-related autopsies have shown evidence of a recent MI. A greater proportion of autopsies (40-70%) show evidence of a healed MI. Many of these hearts also reveal evidence of plaque fissuring, hemorrhage, and thrombosis.
The Cardiac Surgery Study (CASS) showed that improving or restoring blood flow to an ischemic myocardium decreased the risk of SCD, especially in patients with 3-vessel disease and heart failure, when compared with medical treatment over a 5-year period.
The efficacy of beta-blocking agents, such as propranolol, in decreasing sudden death mortality, especially when administered to patients who had MI with VF, VT, and high-frequency PVCs, may be due in part to the ability of beta-blockers to decrease ischemia, but they are also effective in patients with nonischemic cardiomyopathy for reduction of SCD. Beta-blockers also increase the VF threshold in ischemic animals and decrease the rate of ventricular ectopy in patients who had MI.
Reperfusion of ischemic myocardium with thrombolysis or direct percutaneous coronary intervention can induce transient electrical instability by several different mechanisms.
Coronary artery spasm is a condition that exposes the myocardium to both ischemia and reperfusion insults. It is occasionally associated with VT, VF, and SCD. Since some of the episodes of coronary vasospasm may be silent, this disease should be considered in a patient with unexplained SCA.[16] The exact mechanism of ventricular arrhythmia in coronary vasospasm is not known, but factors associated with both ischemia and reperfusion may contribute in induction of arrhythmia.
Nonatherosclerotic coronary artery abnormalities, including congenital lesions, coronary artery embolism, coronary arteritis, and mechanical abnormalities of the coronary artery, have been associated with an increased incidence of sudden death.
Nonischemic cardiomyopathies
Patients with nonischemic cardiomyopathies represent the second largest group of patients who experience SCD in the United States. Nonischemic myopathies, for the purpose of this article, can be divided into the categories dilated and hypertrophic.
Dilated cardiomyopathy
Dilated cardiomyopathy can result from prior ischemia and myocardial infarction or from nonischemic causes. Nonischemic dilated cardiomyopathy (DCM) is becoming increasingly more common, with an incidence of approximately 7.5 cases per 100,000 persons each year. Of cases of SCD, 10% are estimated to be attributable to DCM. The prognosis is very poor for these patients, with a 1-year mortality rate of 10-50%, depending on the New York Heart Association functional class; approximately 30-50% of these deaths are SCD.
The causes of DCM are uncertain; viral, autoimmune, genetic, and environmental (alcohol) origins are implicated. The predominant mechanism of death appears to be ventricular tachyarrhythmia, although bradyarrhythmia and electromechanical dissociation also have been observed, especially in patients with advanced LV dysfunction. Extensive fibrosis of the subendocardium, leading to dilated ventricles and subsequent generation of reentrant tachyarrhythmias, is a proposed factor in mechanism of sudden death. Multiple factors have been shown to contribute to increased risk for SCD in this population. The most important hemodynamic predictor is an increase in end-diastolic pressure and subsequent wall tension. Other important factors are increased sympathetic tone, neurohumoral activation, and electrolyte abnormalities.
Many drugs used in the treatment of heart failure, such as antiarrhythmics, inotropic agents, and diuretics, have direct or indirect (eg, through electrolyte abnormalities) proarrhythmic properties, which may provoke arrhythmias in some cases. Potassium-sparing diuretics may be helpful in decreasing SCD.
Nonsustained ventricular tachycardia (NSVT) is common in patients with dilated cardiomyopathy and approximately 80% of persons with DCM have abnormalities on Holter monitoring. Although NSVT may be a marker, it has not been shown to be a reliable predictor of SCD in these patients. Recent studies have shown possibility of increased mortality following suppression of NSVT by antiarrhythmic medications due to proarrhythmic properties of these medications and involvement of several other factors in generation of VT and VF. Given the possibility of sustained VT being the underlying cause, a history of syncope should be aggressively pursued. Unexplained syncope, especially in patients with class 3 or 4 heart failure, has been shown to be a predictor of SCD in most patients with cardiomyopathy
Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is an autosomal-dominant, incompletely penetrant genetic disorder resulting from a mutation in one of the many (>45) genes encoding proteins of the cardiac muscle sarcomere. Among the genetic abnormalities described, mutations in the genes coding for the beta-myosin heavy chains, and cardiac troponin T make up most cases. Other mutations may include alpha-myosin heavy chain MYH6), cardiac troponin C (TNNC1), alpha-tropomyosin (TPM1), myosin binding protein-C (MYBPC3), cardiac troponin (TNNI3), essential and regulatory light-chain genes (MYL3 and MYL2, respectively), cardiac alpha-actin gene (ACTC), and titin (TTN). The incidence of SCD in this population is 2-4% per year in adults and 4-6% per year in children and adolescents. HCM is the most common cause of SCD in people younger than 30 years.
The vast majority of young people who die of HCM are previously asymptomatic. The patients may experience SCD while at rest or with mild exertional activity; however, in a significant portion of these patients, the SCD event occurs after vigorous exertion. HCM is the single greatest cause of SCD in young athletes and, hence, is the major entity for which to screen during the physical examination of an athlete.
The mechanism of SCD in HCM is not entirely understood. Initially, it was thought to be due to obstruction of the outflow tract because of catecholamine stimulation. However, later studies suggested that individuals with nonobstructive HCM are at high risk for SCD as well, primarily related to VT or VF. The mechanism of arrhythmia in this setting is not clear, and hypertrophy may be a part of cardiac remodeling in these patients that provides the substrate for lethal arrhythmia.
Rapid or polymorphic symptomatic NSVT may have better predictive value compared with asymptomatic and monomorphic NSVT. Other clinical markers that may have predictive value for SCD in patients with HCM are young age at onset, thickness of the septum, and family history of SCD.
Arrhythmogenic right ventricular cardiomyopathy
Arrhythmogenic RV cardiomyopathy is characterized by replacement of the RV wall with fibrofatty tissue. Involvement of the interventricular septum and left ventricle is associated with poorer outcomes.
About 30-50% of cases occur as a phenotypically apparent familial disorder. Several genetic defects, including mutations in the desmoplakin domain locus on chromosome 6 and the ryanodine receptor locus on chromosome 1 (although this has been debated), have been correlated with SCD. Again, interstitial fibrosis plays an important role in ventricular arrhythmia in this condition. Autosomal dominant inheritance is common, but autosomal recessive transmission has been reported for select mutations. The autosomal recessive form, Naxos disease (named after the Greek Island), has been reported in a geographically isolated area mainly in Mediterranean countries and is usually associated with wooly hair and palmoplantar keratoderma or similar skin disorder. This disorder is associated with mutation in the gene for plakoglobin, a protein involved in cellular adhesion, found on chromosome 17p.
Arrhythmogenic RV dysplasia affects men more often than women. The annual incidence rate of SCD in this population is approximately 2%. Patients may present with signs and symptoms of RV hypertrophy and dilation, often with sustained monomorphic or polymorphic VT of a left bundle-branch block morphology with an axis usually between negative 90-100°
Atrial arrhythmias may be present in as many as 25% of patients. Syncope and sudden death often are associated with exercise. In many patients, sudden death is the first manifestation of the disease. Clinicians should be alerted to the epsilon wave finding on ECG studies (see the image below). The epsilon wave can be present in as many as 23% of patients after the first VT event. The percentage of patients with the epsilon wave finding on ECG increases to 27% and 34% at 5 and 10 years, respectively, after the first VT event.
View Image | Cardiac death, sudden. Epsilon wave in a patient with arrhythmogenic right ventricular dysplasia. |
Uhl anomaly is a condition in which the RV wall is extremely thin secondary to apposition of endocardial and epicardial layers.
Valvular disease
Prior to the advent of surgical therapy for valvular heart disease, SCD was fairly common in patients with progressive aortic stenosis.
Most aortic stenosis deaths were sudden. In a study by Chizner et al of 42 patients who had isolated aortic stenosis and did not undergo valve replacement, as many as 56% of deaths were sudden at 5 years of follow-up. Of these 42 patients, 32 were symptomatic and 10 were asymptomatic.[17]
The mechanism of sudden death is unclear, and both malignant ventricular arrhythmia and bradyarrhythmia have been documented.
The incidence of SCD has decreased significantly with advent of aortic valve replacement. However, it still accounts for the second most common cause of death postoperatively in this population and especially in those with prosthetic and heterograft aortic valve replacement. The incidence of SCD after aortic valve surgery is highest in the first 3 weeks after the procedure and then plateaus at 6 months of follow-up.
Other valvular lesions
The risk of SCD is much lower in other valvular diseases compared with aortic stenosis.
Aortic insufficiency usually presents with signs of heart failure and progressive LV dilatation. As part of this process, reentrant or automatic ventricular foci may develop and ultimately lead to a symptomatic ventricular arrhythmia. After valve replacement, LV wall tension can be expected to reduce and the risk of arrhythmia can be expected to decrease.
Mitral stenosis is becoming increasingly uncommon in the United States because of widespread use of antibiotics in primary streptococcal infections. SCD due to mitral stenosis is very rare.
The incidence of SCD is low in patients with mitral valve prolapse (MVP). MVP has a 5-7% incidence in the general population. In clinically significant MVP, the risk of SCD seems to rise along with total mortality. Kligfield et al estimated that the incidence of sudden death varies with the presence of symptoms and the severity of mitral regurgitation. Ventricular tachyarrhythmias are the most frequent arrhythmia in patients with SCD. Risk factors for SCD to consider in these patients include a family history of SCD, echocardiographic evidence of a redundant mitral valve, repolarization abnormalities, and lengthening of the corrected QT interval (>420 ms in women and >450 ms in men).
Congenital heart disease
In the pediatric and adolescent age groups, SCD occurs with an incidence of 1.3-8.5 cases per 100,000 patients annually, accounting for approximately 5% of all deaths in this group. The causes of SCD are much more diverse in children than adults. In reviewing 13 studies involving 61 children and adolescents with SCD, Driscoll found 50% of cases were due to HCM; 25% were due to anomalous origin of the left coronary artery; and the remaining patients had aortic stenosis, cystic medial necrosis, and sinus node artery obstruction. The following is a classification of SCD in the pediatric population.
In patients with known, previously recognized (including repaired) congenital heart disease, abnormalities associated with SCD include the following:
In patients with known, previously recognized (including repaired) heart disease, acquired causes of SCD include the following:
Kawasaki syndrome
DCM or myocarditis
In patients with previously unrecognized heart disease who have structural heart disease, causes of SCD include the following:
In patients with previously unrecognized heart disease who do not have structural heart disease, causes of SCD include the following:
Long QT syndrome
WPW syndrome
Primary ventricular tachycardia and ventricular fibrillation
Primary pulmonary hypertension
Commotio cordis - Traumatic blow to the chest wall (eg, from a hockey puck or baseball) causing VT/VF and SCD in the absence of significant identifiable trauma
The predominant mechanism is ventricular arrhythmias. In tetralogy of Fallot after postoperative correction of the anomaly, as many as 10% of these patients have VT and the incidence of sudden death is 2-3%. In the Fontan procedure, ie, to correct a physiologic single ventricle, even atrial arrhythmias can cause severe hemodynamic compromise and arrhythmic death. Patients who develop secondary pulmonary hypertension (Eisenmenger syndrome), despite attempted correction of the anatomic defects, have a very poor prognosis. The terminal event may be bradycardia or VT progressing to VF.
Primary electrophysiologic abnormalities
This generally represents a group of abnormalities in which patients have no apparent structural heart disease but have a primary electrophysiologic abnormality that predisposes them to VT or VF. Some imaging techniques have detected abnormal sympathetic neural function in these patients. An ECG study can provide clues to the diagnosis; consider a familial component to these conditions. Normal early repolarization may be associated with increased SCD, though this often represents a benign finding.[18]
Results from the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER) suggest early repolarization is present in a significant proportion of causally diagnosed and idiopathic VF.[19]
Long QT syndrome
Idiopathic long QT syndrome, in which patients have a prolonged QT with a propensity to develop malignant ventricular arrhythmias, is a rare familial disorder.
Two inheritance patterns of congenital long QT syndrome have been described. The Jervell-Lange-Nielsen syndrome, associated with congenital deafness, has an autosomal-recessive pattern of inheritance. The Romano-Ward syndrome is not associated with deafness and has an autosomal dominant pattern of inheritance with variable penetration. This syndrome accounts for 90% of long QT syndrome cases. More than 200 mutations in the 10 or more genes related to long QT syndrome have been found. Among the most common are mutations of SCN5A on chromosome 3, the HERG gene on chromosome 7, and the KVLTQT1 gene on chromosome 11.
Alteration in the function of a myocellular channel protein that regulates the potassium flux during electrical repolarization is thought to be causative, though in some subsets of long QT syndrome, such as those with mutations in SCN5A (long QT3), Na channels are primarily impaired. A relationship with sympathetic nervous system imbalance also appears to exist. The prolongation that occurs makes these patients susceptible to develop a specific form of VT called torsade de pointes.
The clinical course of patients with long QT syndrome is quite variable, with some patients remaining asymptomatic while others develop torsade de pointes with syncope and sudden death. Symptoms and SCD are more common among homozygous individuals (those with two copies of the mutant allele), compared with heterozygous individuals (who have a single mutant allele). The risk of SCD is impacted by environmental factors such as hypokalemia, medications and the presence of sinus pauses. SCD in these patients also has been associated with emotional extremes, auditory auras or stimulation, and vigorous physical activity. Symptoms usually begin in childhood or adolescence.
The probability that a specific patient has congenital long QT syndrome is divided to low, intermediate, and high probability based on the following criteria: (1) ECG criteria including long QT, torsade de pointes, notched T wave, T wave alternans, bradycardia for age; (2) clinical criteria including syncope with or without stress, deafness; and (3) family history of long QT syndrome or SCD.
When measuring QTc, selecting rhythm strips that have minimal variability of RR intervals and a stable heart rate is important.
Treatment for long QT syndrome includes beta-blockers and often pacemaker or ICD implantation. Beta-blockers decrease the overall mortality in patients with long QT syndrome. However, they do not eliminate the risk of syncope, cardiac arrest, and SCD completely. They are not effective in patients with mutation in Na channel genes (long QT3). Torsade de pointes in patients with long QT syndrome is associated with bradycardia and pauses. Therefore, a pacemaker can prevent torsade de pointes in these patients by preventing bradycardia. ICD therapy may be indicated in patients with recurrent symptoms despite treatment with beta-blockers.
Acquired long QT syndrome
A number of antiarrhythmics (especially class Ia and class III) and other medications, electrolyte abnormalities, cerebrovascular diseases, and altered nutritional states are known to cause QT prolongation and put patients at risk for torsade de pointes. This usually occurs when QT prolongation is associated with a slow heart rate and hypokalemia.
The QT interval is prolonged in as many as 32% of patients with intracranial hemorrhage (especially in subarachnoid hemorrhages). Lesions in the hypothalamus are thought to lead to this phenomenon.
Reports of sudden death due to ventricular arrhythmia in patients with hypocalcemia, hypothyroidism, nutritional deficiencies associated with modified starvation diets, and in patients who are obese and on severe weight-loss programs have been reported.
Class Ia antiarrhythmic drugs that cause acquired long QT syndrome include quinidine, disopyramide, and procainamide. Class III antiarrhythmic drugs that cause acquired long QT syndrome include sotalol, N -acetyl procainamide, bretylium, amiodarone, and ibutilide.
Other drugs that cause acquired long QT syndrome include bepridil, probucol, tricyclic and tetracyclic antidepressants, phenothiazines, Haldol, antihistamines (eg, terfenadine, astemizole), antibiotics (eg, erythromycin, sulfamethoxazole/trimethoprim), chemotherapeutics (eg, pentamidine, anthracycline), serotonin antagonists (eg, ketanserin, zimeldine), and organophosphorus insecticides.
Electrolyte abnormalities that cause acquired long QT syndrome include hypokalemia, hypomagnesemia, and hypocalcemia.
Altered nutritional states and cerebrovascular disease that cause acquired long QT syndrome include intracranial and subarachnoid hemorrhages, stroke, and intracranial trauma.
Hypothyroidism and altered autonomic status (eg, diabetic neuropathy) can cause acquired long QT syndrome.
Hypothermia can cause acquired QT prolongation. The ECG will typically also demonstrate an Osborn wave, a distinct bulging of the J point at the beginning of the ST segment. This ECG finding resolves upon warming.
Short QT syndrome
The short QT syndrome is a newly recognized syndrome, first time described in 2000, which can lead to lethal arrhythmias and SCD. Three mutations in potassium channels have been described that lead to gain of function in potassium channels and shortening of action potential and decreased QT interval.
To diagnose short QT syndrome, the QTc should be less than 330 msec and tall and peaked T waves should be present. Clinical manifestations are variable from no symptoms, to palpitations due to atrial fibrillation, syncope due to VT, and SCD. VF is easily inducible at electrophysiology study in these patients, and SCD can happen at any age.
A study by Gollob et al proposes diagnostic criteria that include QTc interval, J point–to–T peak interval, clinical history (eg, SCA, atrial fibrillation [AF], syncope), family history and genotyping.[20]
Although antiarrhythmic medications, such as sotalol, ibutilide, and procainamide, have been proposed as a therapy (to prolong the QT), data to support this approach are insufficient at present. ICD placement may be considered to prevent VT and SCD, although T-wave oversensing, resulting in inappropriate ICD discharges, has been problematic.
Because no long-term outcome data are available, Giustetto et al investigated the clinical characteristics and the long-term course of a large cohort of patients with short QT syndrome (defined as QT of ≤360 ms). Their findings suggest short QT syndrome carries a high risk of sudden death in all age groups, with the highest risk in symptomatic patients. Hydroquinidine therapy appeared to reduce the antiarrhythmic event rate from 4.9% 0%. However, this was a small registry studying a rare disease; thus, the true benefit is unclear.[21]
Wolff-Parkinson-White syndrome
WPW syndrome is a recognized but rare cause of sudden death. The existence of an atrioventricular accessory pathway in this syndrome results in ventricular preexcitation, which appears with short PR interval, wide QRS complex, and delta wave on ECG. The refractory period in the anterograde direction of accessory pathway determines the ventricular rate in the setting of atrial fibrillation and WPW. Most patients with WPW syndrome and SCD develop atrial fibrillation with a rapid ventricular response over the accessory pathway, which induces VF (see the image below). In a study by Klein et al of 31 patients with VF and WPW syndrome, a history of atrial fibrillation or reciprocating tachycardia was an important predisposing factor. The presence of multiple accessory pathways, posteroseptal accessory pathways, and a preexcited R-R interval of less than 220 ms during atrial fibrillation are associated with higher risk for SCD.
View Image | Cardiac death, sudden. Ventricular fibrillation appeared during rapid atrial fibrillation in a patient with Wolff-Parkinson-White syndrome. |
Symptomatic patients should be treated by antiarrhythmic medications (eg, procainamide), catheter ablation of the accessory pathway, or electrical cardioversion depending on the severity and frequency of symptoms. Asymptomatic patients may be observed without treatment.
Medications such as digoxin, adenosine, and verapamil that block the AV node are contraindicated in patients with WPW and atrial fibrillation because they may accelerate conduction through the accessory pathway, potentially causing VF and SCD.
Brugada syndrome
In 1992, Brugada and Brugada described a syndrome of a specific ECG pattern of right bundle-branch block and ST-segment elevation in leads V1 through V3 without any structural abnormality of the heart, that was associated with sudden death.
In 25-30% of these patients, a mutation in SCN5A on chromosome 3 is detected. This mutation results in a sodium channelopathy. The most common clinical presentation is syncope, and this mutation is most common in young males and in Asians. It is associated with VT, VF, and SCD.
Three ECG types of Brugada pattern are described. Only type 1,- which consists of a coving ST elevation in V1 to V3 with downsloping ST segment and inverted T waves, pseudo RBBB pattern with no reciprocal ST changes and normal QTc, is specific enough to be diagnostic for Brugada syndrome when it is associated with symptoms. The other two ECG patterns of Brugada are not diagnostic, but they merit further evaluation.
The Brugada ECG pattern can be dynamic and not found on an index ECG. When clinical suspicion is high, a challenge test with procainamide or some other Na channel blocker may be diagnostic by reproducing the type 1 ECG pattern.
Although antiarrhythmic medications, catheter ablation and pacemaker therapies all have potential, in young and symptomatic patients, an ICD should be implanted to prevent VF and SCD. ICD therapy is the only proven treatment to date. Whether ICD placement is indicated in older or asymptomatic patients is controversial at present.
A prospective study by Delise et al suggests using a combination of clinical risk factors (syncope and family history of SCD) with VT inducibility in EP study to risk stratify patients with the type 1 ECG pattern of Brugada syndrome.[22]
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a syndrome that presents with polymorphic VT, syncope, or SCD, and in about half of these patients, a mutation in one of two different genes have been detected.
The polymorphic VT is characteristically induced by emotional or physical stress (eg, exercise stress test). The medical therapy of choice is administration of beta-blockers, and ICD may be indicated. New data may support the use of flecainide in the treatment of this disease.[23]
Primary ventricular fibrillation occurs in a structurally normal heart due to idiopathic etiology.
An estimated 3-9% of cases of VT and VF occur in the absence of myocardial ischemia. As many as 1% of patients with out-of-hospital cardiac arrest have idiopathic VF with no structural heart disease. As many as 15% of patients younger than 40 years who experience VF have no underlying structural heart disease. Viskin and Behassan noted that of 54 patients with idiopathic VF, 11 patients had histologic abnormalities on endomyocardial biopsy.
SCD is often the first presentation of VF in patients at risk but who have had no preceding symptoms. In those patients who survive, VF may recur in as many as one third of patients.
The options for medical therapy include beta-blockers and class 1A antiarrhythmic drugs, but limited data are available regarding their efficacy. The mainstay of treatment is preventing VF by ICD placement. Mapping and radiofrequency ablation of the triggering foci is an option for those patients who experience frequent episodes of VF following ICD placement.
Right ventricular outflow tract (RVOT) tachycardia is the most common form of idiopathic VT, comprising 70-80% of all idiopathic VTs. RVOT tachycardia is a very rare cause of SCD. It also has been referred to as exercise-induced VT, adenosine-sensitive VT, and repetitive monomorphic VT.
RVOT tachycardia occurs in patients without structural heart disease and arises from the RV outflow region. Current data suggest that triggered activity is the underlying mechanism of RVOT tachycardia. RVOT tachycardia is believed to be receptor-mediated because exogenous and endogenous adenosine can terminate this process. Maneuvers that increase endogenous acetylcholine also have been demonstrated to antagonize this process.
Symptoms typical of RVOT tachycardia include palpitations and presyncope or syncope, often occurring during or after exercise or emotional stress. VT also can occur at rest. The ECG during VT displays a left bundle-branch block/inferior axis morphology.
Treatment is based on frequency and severity of symptoms. The first line of therapy is a beta-blocker or calcium channel blocker. Patients with symptoms not relieved by medical therapy are best treated with radiofrequency catheter ablation. Successful ablation is reported in 83-100% of cases.
Other causes of sudden death
Two major causes of sudden cardiopulmonary death deserve mention.
Pulmonary embolism is a frequent cause of sudden death in people at risk. Risk factors include previous personal or family history of deep venous thromboembolism, malignancy, hypercoagulable states, and recent mechanical trauma such as hip or knee surgery.
Aortic dissection or aneurysmal rupture is the other major cause of out-of-hospital nonarrhythmic cardiovascular death. Predisposing factors for aortic dissection include genetic deficiencies of collagen such as Marfan syndrome, Ehlers-Danlos syndrome, and aortic cystic medial necrosis.
Medical Care
Advanced cardiac life support (ACLS): In the event of cardiac arrest, the immediate implementation of ACLS guidelines is indicated. Widespread interest in improving rates of public ACLS training with a special emphasis on use of early defibrillation by public service personnel (eg, police, fire, airline attendants) exists. Through these measures, the greatest public health benefits can be achieved in the fight against sudden death. In 2010, the American Heart Association (AHA) published new Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science.[25]
The 2009 American Heart Association Cardiac Arrest Survival Summit released consensus recommendations for implementation strategies to optimize the care of patients with out-of-hospital sudden cardiac arrest (OHCA).[26] These recommendations included collection of national data on OHCA and local culture changes because incomplete implementation of existing standards was seen as the limiting problem.
In general, ACLS guidelines should be followed in all cases of SCA; however, depending on the presented rhythm, the following should be considered in acute therapy of SCA:
Bystander CPR
The best techniques for bystander CPR continue to evolve based on rigorous scientific evaluation and considerations of practical applicability. Recent data suggest, for example, that compression-only CPR may be of equal or greater effectiveness than traditional compression plus ventilation techniques.[27]
Adielsson et al suggest that the long-term perspective data among patients in VF or pulseless VT who were given bystander CPR revealed that survival to 1 month after VF almost doubled.[28]
Berdowski and colleagues in a recent cohort study demonstrated that the bystander use of automated external defibrillators can reduce the time to defibrillation from 11 minutes to 4.1 minutes and improves neurologically intact survival to discharge from 14.3% to 49.6%.[1] That observation is consistent with already known facts that the main initiating mechanisms of sudden cardiac death are ventricular tachycardia and ventricular fibrillation, and that time to defibrillation is a critical factor in restoring the rhythm.
The conclusion that may be drawn from the above studies is that immediate chest compression and defibrillation are the most important interventions to improve the outcome in sudden cardiac arrest, whereas ventilation does not play as important a role.
Ventricular arrhythmia (VF and VT)
Defibrillation is the mainstay of the acute therapy of SCA due to VF or VT. Epinephrine (1 mg q3-5min) or vasopressin (40 U single dose) are given. Amiodarone (300 mg IV push and 150 mg repeat IV push if needed) and lidocaine (1 mg/kg IV push q3-5min up to 3 doses) can be used as antiarrhythmic drugs if defibrillation does not control the VF/VT. In case of polymorphic VT or suspected hypomagnesemia, 1-2 g IV push of magnesium is recommended.
Pulseless electrical activity (PEA)
Epinephrine (1 mg q3-5min) can be used as there is no evidence supporting the use of vasopressin in PEA. Atropine (1 mg q3-5min) should be used in case of bradycardia. Sodium bicarbonate (1 meq/kg) should be given if there is associated hyperkalemia and its use may be considered in long arrest intervals and suspected metabolic acidosis.
Asystole
One study suggested that vasopressin is more effective in acute therapy of asystole than epinephrine.[2] Atropine and sodium bicarbonate are used with similar indications in PEA.
Medical stabilization
Careful postresuscitative care is essential to survival because studies have shown a 50% repeat inhospital arrest rate for people admitted after an SCD event. Treatment of myocardial ischemia, heart failure, and electrolyte disturbances are all justified by the results of multiple acute MI and congestive heart failure randomized trials. Empiric beta-blockers are reasonable in many circumstances because of favorable properties discussed in Causes. Empiric antiarrhythmics, including amiodarone, should not supersede ICD implantation unless control of recurrent VT is needed while the patient is in the hospital.
Therapeutic hypothermia
This intervention limits neurologic injury associated with brain ischemia during a cardiac arrest and reperfusion injury associated with resuscitation.[3]
There are several plausible ways that therapeutic hypothermia may prevent neurologic injury, including reduction in metabolism and oxygen consumption of the brain, inhibition of glutamate and dopamine release, and prevention of oxidative stress and apoptosis. Therefore, therapeutic hypothermia should be considered for patients who have been successfully resuscitated from SCA and who are comatose.
In a prospective study of 1145 consecutive patients with out-of-hospital cardiac arrest who had successful resuscitation, therapeutic hypothermia was associated with increased odds of good neurological outcome (odds ratio, 1.9; 95% confidence interval, 1.18-3.06) in patients with VT or VF.[29]
Therapeutic hypothermia is more effective in patients with initial rhythm of VF/VT but is also recommended for patients presenting with asystole and PEA.
Patients who should not receive this therapy include (1) those with tympanic membrane temperature of below 30ºC at the time of presentation, (2) those who were comatose before SCA, (3) those who are pregnant, (4) those who have inherited coagulation disorders, and (5) those who are terminally ill. Two main techniques for induction of therapeutic hypothermia are surface cooling methods with the use of precooled surface cooling pads and core cooling methods with the use of cold intravenous fluids.
Primary prevention of SCD
Several studies have evaluated the use of prophylactic ICDs in patients who have not yet experienced SCD but are at high risk for future SCD. The first of these trials, Multicenter Automatic Defibrillator Implantation Trail (MADIT) demonstrated that patients with ischemic cardiomyopathy (LVEF ≤35%) and inducible but nonsuppressible VT on EPS had a survival advantage by implanting an ICD.[30]
This study was followed by MADIT-2, demonstrating that post-MI patients with an LVEF ≤30% have a survival benefit with ICD implantation.[31] The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) study showed that implantation of an ICD reduced the risk of sudden cardiac death in a patient population of nonischemic cardiomyopathy (LVEF < 36%) who also had PVCs or nonsustained VT.[32]
Finally, the Sudden Cardiac Death in Heart Failure Trial (SCD-Heft) demonstrated that patients with either ischemic or nonischemic cardiomyopathy on optimal medical therapy, LVEF ≤35%, and NYHA II or III treated with an ICD demonstrate greater survival as compared with either amiodarone or placebo.[33]
The recent Home Automated Defibrillator Trial (HAT) demonstrated no survival benefit for the use of a home AED in patients surviving a recent anterior MI who were not candidates for an ICD.[34] However, the overall mortality and incidence of SCD was much lower than predicted from previous data and the noncardiac mortality was as high as cardiac mortality in the population of this study. These factors led to much less power than initially projected in this trial to detect a significant difference in the mortality rate between the arms.
The use of microvolt T wave alternans (MTWA) to determine which patients with depressed LV systolic function would best benefit from prophylactic ICD placement has been the subject of several recent clinical trials. To date, the results of these clinical trials has not been conclusive.
Author
Ali A Sovari, MD, FACP, FACC, Attending Physician, Cardiac Electrophysiologist, Cedars Sinai Medical Center and St John's Regional Medical Center
Disclosure: Nothing to disclose.
Coauthor(s)
Abraham G Kocheril, MD, FACC, FACP, FHRS, Professor of Medicine, University of Illinois College of Medicine
Disclosure: Nothing to disclose.
Arnold S Baas, MD, FACC, FACP, Professor of Medicine, Division of Cardiology, Fellowship Director for Advanced Heart Failure and Transplant Cardiology, Ahmanson UCLA Cardiomyopathy Center, Mechanical Circulatory Support, and Heart Transplant Program, University of California, Los Angeles, David Geffen School of Medicine; Attending Physician, Ronald Reagan UCLA Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Ronald J Oudiz, MD, FACP, FACC, FCCP, Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Director, Liu Center for Pulmonary Hypertension, Division of Cardiology, LA Biomedical Research Institute at Harbor-UCLA Medical Center
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Actelion, Bayer, Gilead, Lung Biotechnology, United Therapeutics<br/>Received research grant from: Actelion, Bayer, Gilead, Ikaria, Lung Biotechnology, Pfizer, Reata, United Therapeutics<br/>Received income in an amount equal to or greater than $250 from: Actelion, Bayer, Gilead, Lung Biotechnology, Medtronic, Reata, United Therapeutics.
Chief Editor
Jeffrey N Rottman, MD, Professor of Medicine, Department of Medicine, Division of Cardiovascular Medicine, University of Maryland School of Medicine; Cardiologist/Electrophysiologist, University of Maryland Medical System and VA Maryland Health Care System
Disclosure: Nothing to disclose.
Additional Contributors
Russell F Kelly, MD, Assistant Professor, Department of Internal Medicine, Rush Medical College; Chairman of Adult Cardiology and Director of the Fellowship Program, Cook County Hospital
Disclosure: Nothing to disclose.
Acknowledgements
The authors and editors of Medscape Drugs & Diseases gratefully acknowledge the contributions of previous authors Krishna Malineni, MD, and Peter A McCullough, MD, MPH, FACC, FACP, FCCP, to the development and writing of this article.
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