|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2006; 48:247-346, doi:10.1016/j.jacc.2006.07.010
(Published online 25 August 2006). © 2006 by the American College of Cardiology Foundation |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
a France
b Poland
c United Kingdom
d The Netherlands
e Norway
f Greece
g Italy
h Portugal
i Germany
j Spain
 |
Preamble |
|---|
The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The ACC/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. The Task Force is pleased to have this guideline developed in conjunction with the European Society of Cardiology (ESC). Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop or update written recommendations for clinical practice.
Experts in the subject under consideration have been selected from all 3 organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered as well as frequency of follow-up and cost effectiveness. When available, information from studies on cost will be considered; however, review of data on efficacy and clinical outcomes will constitute the primary basis for preparing recommendations in these guidelines.
The ACC/AHA Task Force on Practice Guidelines and the ESC Committee for Practice Guidelines make every effort to avoid any actual, potential, or perceived conflict of interest that might arise as a result of an industry relationship or personal interest of the writing committee. Specifically, all members of the Writing Committee, as well as peer reviewers of the document, were asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest. Writing Committee members are also strongly encouraged to declare a previous relationship with industry that might be perceived as relevant to guideline development. If a Writing Committee member develops a new relationship with industry during his or her tenure, he or she is required to notify guideline staff in writing. The continued participation of the Writing Committee member will be reviewed. These statements are reviewed by the parent Task Force, reported orally to all members of the Writing Committee at each meeting, and updated and reviewed by the Writing Committee as changes occur. Please refer to the methodology manuals for further description of the policies used in guideline development, including relationships with industry, which are available on the ACC, AHA and ESC World Wide Web sites (http://www.acc.org/clinical/manual/manual_introltr.htm, http://circ.ahajournals.org/manual, and http://www.escardio.org/knowledge/guidelines/Rules, respectively). Please see Appendix 1 for author relationships with industry and Appendix 2 for peer reviewer relationships with industry that are pertinent to these guidelines.
|
|
The guidelines will be reviewed annually by the ACC/AHA Task Force on Practice Guidelines and the ESC Committee for Practice Guidelines and will be considered current unless they are updated, revised, or sunsetted and withdrawn from distribution. The executive summary and recommendations are published in the September 5, 2006 issue of the Journal of the American College of Cardiology, September 5, 2006 issue of Circulation, and September 17, 2006 issue of the European Heart Journal. The full-text guideline is e-published in the same issues of the Journal of the American College of Cardiology and Circulation and published in the September 2006 issue of Europace, as well as posted on the ACC (www.acc.org), AHA (www.americanheart.org), and ESC (www.escardio.org) World Wide Web sites. Copies of the full text and the executive summary are available from all 3 organizations.
Sidney C. Smith, Jr., MD, FACC, FAHA, FESC, Chair, ACC/AHA Task Force on Practice Guidelines
Silvia G. Priori, MD, PhD, FESC, Chair, ESC Committee for Practice Guidelines
|
1. Introduction |
|---|
|
The committee was co-chaired by A. John Camm, MD, FACC, FAHA, FESC, and Douglas P. Zipes, MD, MACC, FAHA, FESC. This document was reviewed by 2 official reviewers nominated by the ACC, 2 official reviewers nominated by the AHA, 2 official reviewers nominated by the ESC, 1 official reviewer from the ACC/AHA Task Force on Practice Guidelines, reviewers from the EHRA and HRS, and 18 content reviewers, including members from ACCF Clinical Electrophysiology Committee, AHA Council on Clinical Cardiology, Electrocardiography, and Arrhythmias, and AHA Advanced Cardiac Life Support Subcommittee.
The committee conducted comprehensive searching of the scientific and medical literature on ventricular arrhythmias and sudden cardiac death (SCD). Literature searching was limited to publications on humans and in English from 1990 to 2006. The search parameters were extended for selected topics when a historical reference was needed or if limited studies existed in English. In addition to broad-based searching on ventricular arrhythmias and SCD, specific targeted searches were performed on ventricular arrhythmias and SCD and the following subtopics: mechanisms, substrates, clinical presentations, ECG, exercise testing, echocardiography, imaging, electrophysiological (EP) testing, drug therapy (antiarrhythmic and nonantiarrhythmic), implantable and external cardioverter devices, ablation, surgery, acute specific arrhythmias (e.g., acute coronary syndrome [ACS], heart failure [HF], stable sustained monomorphic ventricular tachycardia [VT], torsades de pointes), specific pathology (e.g., congenital heart disease, myocarditis, endocrine disorders, renal failure), cardiomyopathies, genetic arrhythmias, structurally normal hearts, athletes, elderly, gender, pediatric, and drug-induced arrhythmias. The complete list of keywords is beyond the scope of this section. The committee reviewed all compiled reports from computerized searches and conducted additional manual searching. Literature citations were generally restricted to published manuscripts appearing in journals in the Index Medicus. Because of the scope and importance of certain ongoing clinical trials and other emerging information, published abstracts were cited in the text when they were the only published information available.
The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention for management of patients with ventricular arrhythmias and prevention of SCD summarize both clinical evidence and expert opinion. Once recommendations were written, a Classification of Recommendation and Level of Evidence grade was assigned to each recommendation.
Classification of Recommendations and Level of Evidence are expressed in the ACC/AHA/ESC format as follows:
Classification of Recommendations
Level of Evidence
The schema for classification of recommendations and level of evidence is summarized in Table 2, which also illustrates how the grading system provides an estimate of the size of treatment effect and an estimate of the certainty of the treatment effect.
|
Not all therapeutic combinations are clinically relevant, and many have no evidence base and probably will not have one in the future because of the lack of clinical relevance or the relative rarity of the particular grouping. In many instances, the probable value of therapy may be reasonably inferred by the response of similar patients to specific therapies.
1.2 Prophylactic Implantable Cardioverter-Defibrillator Recommendations Across Published Guidelines. The ACC/AHA/NASPE 2002 Guidelines Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices (1), the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (2), the ESC 2001 and 2003 Guidelines on Prevention of Sudden Cardiac Death (3,4), the ESC 2005 Guidelines for the Diagnosis and Treatment of Chronic Heart Failure (5a), and the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult (6) include a large number of recommendations on ICD therapy that merit attention.
Recommendations for prophylactic ICD implantation based on ejection fractions (EFs) have been inconsistent because clinical investigators have chosen different EFs for enrollment in trials of therapy, average values of the EF in such trials have been substantially lower than the cutoff value for enrollment, and subgroup analyses of clinical trial populations based on EF have not been consistent in their implications. Substantial differences between guidelines have resulted. However, no trial has randomized patients with an intermediate range of EFs. For instance, there is no trial that has specifically studied patients with an LVEF between 31% and 35%, yet recommendations have been set for such patients on the basis of data derived from trials that studied groups with EFs less than or equal to 30%, others that enrolled patients with an EF less than or equal to 35%, and one trial that enrolled patients with an EF less than or equal to 40%. Recognizing these inconsistencies, this Guideline Writing Committee decided to construct recommendations to apply to patients with an EF less than or equal to a range of values. The highest appropriate class of recommendation was then based on all trials that recruited patients with EFs within this range. In this way, potential conflicts between guidelines were reduced and errors due to drawing false conclusions relating to unstudied patient groups were minimized (Table 3).
|
1.3 Classification of Ventricular Arrhythmias and Sudden Cardiac Death. This classification table is provided for direction and introduction to the guidelines (Table 4).
|
|
2. Epidemiology |
|---|
2.1 Ventricular Arrhythmias.
2.1.1 Premature Ventricular Complexes and Nonsustained Ventricular Tachycardia
Single and repetitive forms of PVCs have been studied for their role in risk prediction in several contrasting clinical circumstances, including implications in apparently normal subjects compared with those with identified disease states, in steady-state pathophysiology versus transient events, and in inactive subjects versus those under physical stress. The epidemiological implications vary for each of these contingencies.
2.1.1.1 Premature Ventricular Complexes in the Absence of Heart Disease
Among presumably normal individuals, estimates of the prevalence of PVCs and NSVT vary according to the sampling technique used and the source of data. PVCs were recorded on standard 12-lead electrocardiograms (ECGs) in 0.8% of subjects in a healthy military population, with a range of 0.5% among those under the age of 20 y to 2.2% of those over 50 y of age (12). In a study of middle-aged men, both with and without known heart disease, a 6-h monitor sampling technique identified a 62% incidence of asymptomatic ventricular arrhythmias, more than one half of which were infrequent single PVCs (13). The incidence, frequency, and complexity of ventricular arrhythmias were greater in the presence of known or suspected heart disease, and mortality risk implications were absent in those without heart disease (13,14). In contrast to PVCs and monomorphic patterns of NSVT, polymorphic ventricular tachyarrhythmias in the absence of structural heart disease are indicators of risk (15). Many nonsustained polymorphic VT events occurring in individuals free of grossly evident structural abnormalities of the heart are due to abnormalities at a molecular level or a consequence of electrolyte disturbances or adverse drug effects.
In the Tecumseh, Michigan, communitywide cardiovascular epidemiology study, PVCs in subjects with structurally normal hearts carried no adverse prognostic significance under the age of 30 y, but in those older than 30 y, PVCs and short runs of NSVT began to influence risk (16). More recent studies provide conflicting implications regarding risk in asymptomatic subjects. In one study (17), asymptomatic ventricular arrhythmias in the absence of identifiable heart disease predicted a small increase in risk, while another study (18) suggested no increased risk.
In contrast to the apparently non–life-threatening implication of PVCs at rest, PVCs elicited during exercise testing, even in apparently normal individuals, appear to imply risk over time. In one study (19), PVCs and NSVT induced during exercise correlated with increased risk of total mortality, while in another study (20), both exercise- and recovery-phase PVCs correlated with risk, with the greater burden associated with recovery-phase arrhythmias. A selection bias, based on indications for stress testing, may have influenced these observations (21).
2.1.1.2 Premature Ventricular Complexes in the Presence of Established Heart Disease
PVCs and runs of NSVT in subjects with structural heart disease contribute to an increased mortality risk, the magnitude of which varies with the nature and extent of the underlying disease. Among survivors of myocardial infarction (MI), frequent and repetitive forms of ventricular ectopic activity, accompanied by a reduced EF, predict an increased risk of SCD during long-term follow-up (21–23). Most studies cite a frequency cutoff of 10 PVCs per hour and the occurrence of repetitive forms of ventricular ectopy as thresholds for increased risk. Several investigators have emphasized that the most powerful predictors among the various forms of PVCs are runs of NSVT (21,22). Although the specificity of this relationship is now questioned. The power of risk prediction conferred by the presence of PVCs and NSVT appears to be directly related to the extent of structural disease as estimated by EF and to cardiovascular limitations as estimated by functional capacity (24).
Ventricular arrhythmias during ambulatory recording in patients with HF do not specifically predict risk for SCD (25). Risk is already high because of the underlying disease. Suppression of ambient ventricular arrhythmias is no longer considered a therapeutic target for prevention of death in the post-MI or nonischemic cardiomyopathy subgroups.
2.1.2 Ventricular Tachycardia and Ventricular Fibrillation During Acute Coronary Syndromes
Observations of both post-MI patients (26) and survivors of cardiac arrest that occurred during the acute phase of transmural MI (27) suggest that life-threatening ventricular tachyarrhythmias occurring during the first 24 to 48 h of MI do not imply continuing risk over time. A study done on follow-up after in-hospital VF does suggest an adverse prognosis over the ensuing 6 mo (28), but the patients were not selected for acute-phase arrhythmias. Later in-hospital VF has previously been reported to confer long-term risk (29). In contrast, patients presenting with non–ST-elevation myocardial infarction (NSTEMI) are at increased long-term risk of SCD (30), possibly related in part to a persistent propensity for ventricular tachyarrhythmias (31). Such patients have generally been excluded from clinical trials for interventions targeting long-term arrhythmic death risk because of low absolute risk, but it remains unclear whether the magnitude of risk is modulated by the extent of myocardial damage that occurs during the acute event. The long-term risk implications of sustained VT and VF during the acute phase of MI may also be applied to frequent PVCs and runs of NSVT (32). It is important to stress that the clinician’s ability to recognize individuals with reversible or transient causes of ventricular tachyarrhythmias is limited (33).
2.2 Sudden Cardiac Death.
2.2.1 Incidence of Sudden Cardiac Death
The geographical incidence of SCD varies as a function of CHD prevalence in different regions (3). Estimates for the United States (34–38) range from less than 200,000 to more than 450,000 SCDs annually, with the most widely used estimates in the range of 300,000 to 350,000 SCDs annually (39). The variation is based, in part, on the inclusion criteria used in individual studies. Overall, event rates in Europe are similar to those in the United States (3), with significant geographic variations reported.
The temporal definition of SCD strongly influences epidemiological data (40). The proportion of all natural deaths due to SCD is 13% when a definition of 1 h from onset of symptoms is used. In contrast, the communitywide study in Maastricht, the Netherlands, reported that 18.5% of all deaths were SCD, using a 24-h definition (41). The application of a 24-h definition of SCD increases the fraction of all natural deaths falling into the "sudden" category but reduces the proportion of all sudden natural deaths that are due to cardiac causes (40).
Approximately 50% of all CHD deaths are sudden and unexpected, occurring shortly (instantaneous to 1 h) after the onset of a change in clinical status, with some geographical variation in the fraction of coronary deaths that are sudden (42). The decreasing age-adjusted CHD mortality does not imply a decrease in absolute numbers of cardiac or sudden deaths (43,44) because of the growth and aging of the U.S. and European populations and the increasing prevalence of chronic heart disease (45).
2.2.2 Population Subgroups and Risk Prediction
Three factors affect the ability to identify subjects and population subgroups at risk and consideration of strategies for prevention of SCD:
|
2.2.3 Time-Dependent Risk
The risk of SCD after a clinical event is not linear as a function of time (39,46). Survival curves after major cardiovascular events, which identify risk for both sudden and total cardiac death, demonstrate that the most rapid rate of attrition usually occurs during the first 6 to 18 mo after the index event. Curves with these characteristics have been generated from data on survivors of out-of-hospital cardiac arrest, new onset of HF, and unstable angina and on high-risk subgroups of patients with recent MI. In contrast to inherent (baseline) risk patterns over time, however, benefit patterns from controlled trials may show divergence of curves early (e.g., post-MI beta-blocker therapy, clopidogrel in ACSs) or later (e.g., angiotensin-converting enzyme [ACE] inhibitors and statins). Mortality is highest in the first month after acute MI (AMI) in patients with EF of less than 30% (47).
2.2.4 Age, Heredity, Gender, and Race
The incidence of SCD increases as a function of advancing age (48), in parallel with the age-related increase in the incidence of total CHD deaths, but may undergo a relative decrease in the eighth decade and beyond because of competing causes of death. The incidence is 100-fold less in adolescents and adults younger than 30 y (1 in 100 000 per year) than it is in adults older than 35 y (49–51). The proportion of coronary deaths and of all cardiac causes of death that are sudden is highest in the younger age groups.
Hereditary factors that contribute to CHD risk have been thought to operate nonspecifically for the SCD syndrome. However, several studies have identified mutations and relevant polymorphisms along multiple steps of the cascade from atherogenesis to plaque destabilization, thrombosis, and arrhythmogenesis, each of which is associated with a risk of a coronary event (52–55). Integration of these individual markers may provide more powerful individual risk prediction in the future (56). In addition, 2 population studies suggest that SCD, as an expression of CHD, clusters in specific families (57,58). There is a large preponderance of SCD in males compared with females during the young adult and early middle-age years because of the protection females enjoy from coronary atherosclerosis before menopause (59–61). As coronary event risk increases in postmenopausal women, SCD risk increases proportionately. Even though the overall risk is much lower in younger women, the established coronary risk factors are still predictive of events (59,61–63).
Studies comparing racial differences in risk of SCD among whites and African Americans with CHD in the United States have yielded conflicting and inconclusive data. However, some studies have demonstrated excess risk of cardiac arrest and SCD among African Americans compared with whites (61,64). SCD rates among Hispanic populations were lower (61).
2.2.5 Risk Profiles and Sudden Cardiac Death
Biological and behavioral risk profiling for coronary artery disease, using the conventional risk factors for coronary atherogenesis (65), is useful for identifying levels of population risk but has limited value for distinguishing individual patients at risk for SCD. Multivariate analyses of selected risk factors for atherogenesis have determined that approximately one half of all SCDs occur among the 10% of the population in the highest risk decile. Thus, the cumulative risk associated with conventional risk factors for coronary atherosclerosis exceeds the simple arithmetic sum of the individual risks (65). The comparison of risk factors in the victims of SCD with those in people who developed any manifestations of coronary artery disease does not provide useful patterns. In addition, certain angiographic and hemodynamic patterns discriminate SCD risk from non-SCD risk only under limited conditions (66).
Markers of risk that move beyond the direct lipid deposition concept of atherogenesis into more complex pathobiology are now being identified, largely focusing on mechanisms responsible for destabilization of lipid-laden plaques. Inflammatory markers, such as C-reactive protein and other indicators of inflammation and destabilization (67), have entered into risk formulations, offering potentially useful additions to conventional risk markers (68,69). In addition, familial clustering of SCD as a specific manifestation of the disease (57,58) may lead to identification of specific genetic abnormalities that predispose to SCD (52–54,70).
Hypertension is an established risk factor for CHD and also emerges as a risk factor for SCD (71). Both the ECG pattern of left ventricular hypertrophy (LVH) and echocardiographic evidence or LVH are associated with a higher proportion of sudden and unexpected cardiac death. Intraventricular conduction abnormalities such as left bundle-branch block (LBBB) are also suggestive of a disproportionate number of SCD (72,73).
There are also meaningful associations between cigarette smoking, obesity, diabetes, and lifestyle and SCD. The Framingham Study demonstrates that cigarette smokers have a 2- to 3-fold increase in SCD risk; this is one of the few risk factors in which the proportion of CHD deaths that are sudden increases in association with the risk factor (72). In addition, in a study of 310 survivors of out-of-hospital cardiac arrest, the recurrent cardiac arrest rate was 27% at 3 y of follow-up among those who continued to smoke after their index event, compared with 19% in those who stopped (74). Obesity is a second factor that appears to influence the proportion of coronary deaths that occur suddenly (72).
Associations between levels of physical activity and SCD have been studied, with varying results (75). A high resting heart rate with little change during exercise and recovery is a risk factor for SCD. Epidemiological observations have suggested a relationship between sedentary activity and increased CHD death risk. The Framingham Study, however, showed an insignificant relationship between low levels of physical activity and incidence of SCD but a high proportion of sudden to total cardiac deaths at higher levels of physical activity (72). An association between acute physical exertion and SCD demonstrated a 17-fold relative increase for the risk of SCD during vigorous exercise for the entire populations (active and inactive). For the habitually inactive, the relative risk was 74 (76). Habitual vigorous exercise attenuates risk (76,77). Therefore, these data indicate that, while the risk of cardiac arrest is higher during vigorous exercise (especially among individuals who are usually sedentary), habitual exercise attenuates the risk of cardiac arrest, both during exercise and at rest (78).
The magnitude of recent life changes in the realms of health, work, home, and family and personal and social factors have been related to MI and SCD (79–82). There is an association between significant elevations of life-change scores during the 6 mo before a coronary event, and the association is particularly striking in victims of SCD. After controlling for other major prognostic factors, the risk of SCD and total mortality is increased by social and economic stresses (83), and alteration of modifiable lifestyle factors has been proposed as a strategy for reducing risk of SCD in patients with CHD (84). Acute psychosocial stressors have been associated with risk of cardiovascular events, including SCD (85,86). The risk appears to cluster around the time of the stress and appear to occur among victims at preexisting risk, with the stressor simply advancing the time of an impending event (85). The possibility of physical stress–induced coronary plaque disruption has also been suggested (87).
|
3. Mechanisms and substrates |
|---|
Genetic influences modulate the risk of SCD in the setting of coronary (and likely other) heart disease (3,55,102). The Paris Prospective Study I, analyzing more than 7000 men followed for an average of 23 y, found that a parental history of SCD increased the relative risk of SCD for offspring to 1.8, without elevating the risk for MI. When both parents had SCD, the relative risk for SCD in offspring was 9.4 (58). A retrospective study performed on cardiac arrest survivors in King County, Washington, also reported family history to be a significant, independent risk for SCD, with an odds ratio of 1.57 (57). Genetic influences may act through multiple, though, not necessarily exclusive mechanisms: by modulating the fixed substrate, atherothrombosis, electrogenesis impulse propagation, neural control and regulation.
In 5% to 10% of cases, SCD occurs in the absence of CHD or cardiomyopathy. There exists a group of inherited abnormalities such as the long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome, and catecholaminergic VT, which can precipitate SCD without overt structural changes in the heart (103–105). Abnormalities in potassium and sodium channels, in ankyrin B, and in the ryanodine receptor of the sarcoplasmic reticulum which is responsible for release of the calcium required for cardiac muscle contraction, can disrupt the normal electrical processes of the heart to cause life-threatening ventricular arrhythmias. It is important to stress that some individuals can have inherited abnormalities that are not manifest until triggered by an external event. For example, autonomic modulation associated with certain types of activity, as well as drugs that affect cardiac repolarization, can convert a subclinical genetic abnormality to SCD. It is highly likely that additional genetic causes of SCD will be found in the future (56).
Among the genetic factors, the most common are DNA variants called "polymorphisms" that may be present in a large proportion of the population and create susceptibility for SCD. Single nucleotide polymorphisms (SNPs) are DNA variants that can be associated with a functional consequence. For example, a polymorphism identified in the alpha 2b adrenergic receptor is associated with an increased risk of MI and SCD (106). Studies such as these require validation before they enter clinical practice. Nevertheless, because millions of SNPs are present in the DNA of each individual, a specific combination of polymorphisms in different genes, interacting with a specific trigger or substrate, may be required to create a risk for SCD (56).
3.2 Mechanisms of Sudden Cardiac Death. The rhythm most often recorded at the time of sudden cardiac arrest is VF. Previous studies suggest that 75% to 80% occur via this mechanism and 15% to 20% are attributed to bradyarrhythmias, including advanced atrioventricular (AV) block and asystole (107). Bayes de Luna et al. (108) noted that in 157 ambulatory patients who had SCD while undergoing Holter recording, 62.4% had VF, 16.5% had bradyarrhythmias, 12.7% had torsades de pointes, and 8.3% had primary VT. The true incidence of bradyarrhythmias is not clear because a rhythm beginning as VF may appear to be asystole when the first ECG is recorded. However, a study reported by Cobb et al. (37) suggests that VF accounts for a smaller proportion of events than previously thought. Advanced AV block or significant bradycardia can cause VF. It is difficult to identify accurately the EP mechanism(s) responsible for SCD. The reason for this is that the mechanisms may be multifactoral and are quite likely to be different depending on the specific cardiac abnormality and a rhythm can start via one mechanism and be perpetuated via another. It is also important to remember that while many studies have investigated EP mechanisms responsible for the onset of VT and VF and their continuation, no class I or III antiarrhythmic agent (109) has clearly been demonstrated to reduce total and SCD mortality in patients at risk for SCD (7a, 109). In fact, it is the drugs without direct EP actions on cardiac muscle or specialized conducting tissue that have been shown effective for prevention of SCD. These drugs include beta blockers, ACE inhibitors, angiotensin receptor–blocking agents, lipid-lowering agents, spironolactone, and fibrinolytic and antithrombotic agents; some data also suggest a protective effect of n-3 fatty acids (110), although this remains to be confirmed (111) (see Section 6.4).
Because SCD is for the most part the result of a ventricular tachyarrhythmia, these drugs must be acting on the fundamental biochemical, ischemic, fibrotic, or other processes that underlie the onset or maintenance of the life-threatening ventricular arrhythmias. Thought of in this fashion, VF can be considered a final common pathway for the expression of an electrically unstable heart. The fundamental mechanisms of cardiac arrest include electromechanical dissociation, asystole and heart block, and VF, with VF being the most common. It is the "upstream" events triggering the electrical instability upon which these drugs probably act. While we unquestionably need to pursue investigations into the electrophysiology of these ventricular tachyarrhythmias, more study needs to be applied to the drugs affecting upstream events, because these events appear to yield the greatest dividends, at least for the present, and must be the reason why the asymptomatic, apparently stable, individual suddenly develops SCD at a particular time on a particular day. It must be that a dynamic factor or factors, possibly transient, interact with a fixed substrate to precipitate the arrhythmia. The possibilities fill a long list and include such things as physical activity, transient ischemia, pH and electrolyte changes, inflammation, hypoxia, stretch, ion channel abnormalities, neuroendocrine actions, drugs, and so forth, all of which are capable of modulating conduction in ways we mostly do not understand. More permanent changes could also occur, such as plaque rupture, as mentioned earlier (112).
|
4. Clinical presentations of patients with ventricular arrhythmias and sudden cardiac death |
|---|
|
4.2 Symptoms Potentially Related to Ventricular Arrhythmias. Palpitations or a perception of cardiac rhythm irregularity may be caused by the whole spectrum of arrhythmias and are also frequently reported in patients in the absence of any arrhythmia (119). Less frequently, patients with VT may present with symptoms of paroxysmal dyspnea or chest pain in the absence of a sensation of rapid heart beating. In such instances, the dyspnea or chest pain may be related to the hemodynamic consequences of tachycardia. "Presyncope" is a vague term that is poorly defined but probably is interpreted by most as a feeling of impending syncope (120). It is not specific as a symptom. VT may be a cause of undiagnosed syncope, especially in patients with structural heart disease (121). Patients with poor ventricular function and inducible VT or VF have a high incidence of subsequent appropriate therapies when implanted with an ICD (122–128). Similar patients with poor ventricular function may be at risk of SCD (129). Patients with sudden onset of very rapid VT such as torsades de pointes with the repolarization syndromes will typically present with syncope or seizure rather than an awareness of rapid heart beating or palpitations (130).
4.2.1 Hemodynamically Stable Ventricular Tachycardia
Patients with slower, stable VT may be asymptomatic but more frequently present with a sensation of rapid heart beating possibly accompanied by dyspnea or chest discomfort. The stability or tolerance of VT is related to the rate of tachycardia, presence of retrograde conduction, ventricular function, and the integrity of peripheral compensatory mechanisms. A presentation with stable, relatively well-tolerated VT does not suggest the absence of heart disease and can be observed in patients with very poor LV function. Even patients with poor ventricular function may not be aware of palpitations during VT. Presentation with stable VT does not in itself indicate a benign prognosis in patients with significant heart disease (131). Incessant VT, although hemodynamically stable, can be a cause of hemodynamic deterioration leading to HF (132). In patients with an ICD, the VT rate can fall below the lower rate of VT detection, causing underdetection of VT that can prevent arrhythmia termination. Immediate reinitiation of the VT following proper ICD therapy can also result in hemodynamic deterioration and an early battery depletion (132,133).
4.2.2 Hemodynamically Unstable Ventricular Tachycardia
The term "hemodynamically unstable" has not been rigidly defined but is widely used. It connotes a tachycardia associated with hypotension and poor tissue perfusion that is considered to have the imminent potential to lead to cardiac arrest or shock if left untreated. Hemodynamically unstable VT is usually, but not exclusively, observed in patients with poor ventricular function. Patients with normal ventricular function can have unstable VT or VF if the tachycardia is rapid enough, as in the LQTS and other abnormal repolarization syndromes (103). Some patients with a normal heart and idiopathic monomorphic VT or even supraventricular tachycardia (SVT) can become hypotensive during the arrhythmia because of a vasovagal reaction.
4.3 Sudden Cardiac Arrest. Rapid sustained VT or VF results in presentation with markedly impaired tissue perfusion and loss of consciousness as a result of inadequate cardiac output, leading to SCD if not expediently reversed. Sudden cardiac arrest may be the presenting symptom with any cardiac disease or even in individuals with no apparent heart disease (44). The initiating mechanism of sudden cardiac arrest may or may not be related to arrhythmia.
|
5. General evaluation of patients with documented or suspected ventricular arrhythmias |
|---|
5.2 Noninvasive Evaluation.
5.2.1 Resting Electrocardiogram
Recommendations
Class I
A standard resting 12-lead ECG allows not only identification of various congenital abnormalities associated with ventricular arrhythmias and SCD (e.g., LQTS, SQTS, Brugada syndrome, ARVC) but also identification of various other ECG parameters, such as those due to electrolyte disturbances, or evidence suggesting underlying structural disease, such as bundle-branch block, AV block, ventricular hypertrophy, and Q waves indicative of ischemic heart disease or infiltrative cardiomyopathy. QRS duration and repolarization abnormalities are both independent predictors of SCD. A prolonged QRS duration greater than 120 to 130 ms has been shown in a number of studies to be associated with increased mortality in patients with a reduced LVEF (equal to or less than 30%). Prospective studies have also reported an association between ST-segment depression or T-wave abnormalities and increased risk of cardiovascular death and SCD in particular. These studies have demonstrated a risk ratio for cardiovascular death of 2.16 (95% confidence interval [CI] 1.30 to 3.58) to 2.4 (95% CI 1.70 to 3.53) in the presence of an "ischemic" ECG (134) and 4.4 (95% CI 2.6 to 7.4) for SCD in the presence of an abnormal T-wave axis (135,136). A prolonged QTc interval is also an independent predictor of SCD. QTc greater than 420 ms has been shown to have a higher risk of cardiovascular death relative to a shorter QTc. And a QTc greater than 440 ms significantly predicted cardiovascular death with adjusted relative risk of 2.1 (137). Although a prolonged QTc interval predicts SCD, it is worth noting that some data suggest that the correlation between QTc and survival may be "J-shaped." In other words, relatively short QTc intervals have also been associated with increased risk. For instance, it has been reported that patients with a mean QTc shorter than 400 ms during 24-h ECG have a more than 2-fold risk of dying suddenly than do patients with a mean QTc between 400 and 440 ms after a 2-y follow-up (138). A QTc less than 300 ms is often used to define the SQTS, which is an independent predictor of SCD (139,140).
5.2.2 Exercise Testing
Recommendations
Class I
Class IIa
Class IIb
Class III
Exercise-ECG is commonly used in the evaluation of patients with ventricular arrhythmias. Its most common application is for detection of silent ischemia in patients suspected of having underlying CHD (141). In patients with known or silent CHD or cardiomyopathies, the presence of frequent PVCs during or after exercise has been associated with greater risk for serious cardiovascular events but not specifically SCD (19,20,24). Exercise-induced PVCs in apparently normal individuals should not be used to dictate therapy unless associated with documented ischemia or sustained VT. With the exception of beta blockers, at the present time the use of antiarrhythmic drugs to abolish exercise-induced PVCs has not been proved to be effective in reducing SCD.
Exercise testing in adrenergic-dependent rhythm disturbances, including monomorphic VT and polymorphic VT, may be useful in evaluating symptomatic subjects and evaluating response to therapy. Ambulatory ECG or event monitoring may fail to capture the arrhythmia, particularly if the patient is relatively sedentary. Moreover, exercise testing may provide prognostic information in these patients, given that the presence of exercise-induced ventricular ectopy increases mortality at 12 mo by 3-fold relative to patients with ectopy at rest only (142). Patients with exercise-induced paired ventricular complexes or VT have a lower survival rate than those with exercise-induced simple ventricular ectopy (143).
Although the safety of supervised exercise testing is well established, less data are available in patients at risk for serious ventricular arrhythmias. In one series, exercise testing in patients with life-threatening ventricular arrhythmias was associated with a 2.3% incidence of arrhythmias requiring cardioversion, intravenous drugs, or resuscitation (144). Such an exercise study may still be warranted because it is better to expose arrhythmias and risk under controlled circumstances. Exercise testing should be performed where resuscitation equipment and trained personnel are immediately available.
5.2.3 Ambulatory Electrocardiography
Recommendations
Class I
The use of continuous or intermittent ambulatory recording techniques can be very helpful in diagnosing a suspected arrhythmia, establishing its frequency, and relating symptoms to the presence of the arrhythmia. Silent myocardial ischemic episodes may also be detected. A 24- to 48-h continuous Holter recording is appropriate whenever the arrhythmia is known or suspected to occur at least once a day. For sporadic episodes producing palpitations, dizziness, or syncope, conventional event monitors are more appropriate because they can record over extended periods of time (145).
New implantable recorders are capable of monitoring the rhythm and can record on patient activation or automatically for prespecified criteria. Although these devices require surgical implantation, they have been shown to be extremely useful in diagnosing serious tachyarrhythmias and bradyarrhythmias in patients with life-threatening symptoms such as syncope (120,146).
5.2.4 Electrocardiographic Techniques and Measurements
Recommendations
Class IIa
Class IIb
ICD trials, especially Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, have highlighted the need to develop novel tools in order to identify patients at highest risk of ventricular arrhythmias and SCD. Numerous modalities exist at present for assessing this risk but only 2 are currently approved by the U.S. Food and Drug Administration (FDA): SAECG and TWA. However, HRV and baroflex sensitivity also show considerable promise. SAECG improves the signal-to-noise ratio of a surface ECG, permitting the identification of low-amplitude (microvolt level) signals at the end of the QRS complex referred to as "late potentials." Late potentials indicate regions of abnormal myocardium demonstrating slow conduction, a substrate abnormality that may allow for reentrant ventricular arrhythmias, and they are believed to serve as a marker for the presence of an EP substrate for reentrant ventricular tachyarrhythmias. The presence of an abnormal SAECG was shown to increase the risk of arrhythmic events by 6- to 8-fold in a post-MI setting (147). However, the restoration of patency to the infarct-related coronary artery with fibrinolysis or angioplasty and the widespread use of surgical revascularization have modified the arrhythmogenic substrate, leading to a noticeable reduction in the predictive power of this tool. SAECG in isolation, therefore, is no longer useful for the identification of post-MI patients at risk of ventricular arrhythmias. However, a high n
Top
Preamble
1. Introduction
