Sudden cardiac death usually occurs secondary to a ventricular tachyarrhythmia. Even under ideal circumstances only 20% of patients who have an out-of-hospital cardiac arrest survive to hospital discharge. Therefore, aggressive treatment and screening of high-risk patients are mandatory to improve survival rates. Risk stratification of high-risk patients, such as the post-myocardial infarction (MI) population, has been of limited value. Between 70% and 85% of "high-risk" post-MI patients, as defined by these screening tests, will not have a sustained ventricular tachyarrhythmia over several years of follow-up. The use of beta-blockers and possibly amiodarone may have some benefit in reducing mortality in high-risk patients after an MI. Several ongoing trials are studying the use of serial drug testing, amiodarone, and implantable cardioverter-defibrillators in reducing the incidence of sudden cardiac death in patients with potentially lethal ventricular arrhythmias. Although implantable cardioverter-defibrillators appear to be superior to antiarrhythmic drugs in reducing sudden cardiac death, total mortality may not be altered. In sustained ventricular tachyarrhythmias, sotalol and amiodarone appear to be superior to other drugs in preventing arrhythmia recurrence. Ongoing trials, such as the Antiarrhythmic Drug versus Implantable Device (AVID) trial may define the best strategy in these high-risk patients.

This Quick Reference Guide for Clinicians contains recommendations on the care of patients with unstable angina based on a combination of evidence obtained through extensive literature reviews and consensus among members of an expert panel. Principal conclusions include the following. (1) Many patients suspected of having unstable angina can be discharged home after adequate initial evaluation. (2) Further outpatient evaluation may be scheduled for up to 72 hours after initial presentation for patients with clinical symptoms of unstable angina judged at initial evaluation to be at low risk for complications. (3) Patients with acute ischemic heart disease judged to be at intermediate or high risk of complications should be hospitalized for careful monitoring of their clinical course. (4) Intravenous thrombolytic therapy should not be administered to patients without evidence of ST segment elevation and acute myocardial infarction. (5) Assessment of prognosis by noninvasive testing often aids selection of appropriate therapy. (6) Coronary angiography is appropriate for patients judged to be at high risk for cardiac complications or death based on their clinical course or results of noninvasive testing. (7) Coronary artery bypass surgery should be recommended for almost all patients with left main disease and many patients with three-vessel disease, especially those with left ventricular dysfunction. (8) The discharge care plan should include continued monitoring of symptoms; appropriate drug therapy, including aspirin; risk-factor modification; and counseling.

Apoptosis and necrosis are two distinctly different forms of cell death, and both occur in the human heart. In contrast to necrosis, apoptosis is not associated with inflammation for two reasons. First, the apoptotic cell does not swell or rupture before it is engulfed by either a macrophage or even a neighboring like cell. Second, the phagocytosis occurs with unusual rapidity. Apoptosis, also thought of as cell suicide, is a tidy way of removing cells no longer useful, in essence a form of selective deletion. These features make apoptosis a valuable component of morphogenesis, mediation of hormonal and immunologic responses, and the homeostatic balance between hypertrophy and atrophy or involution. In the human heart apoptosis has been found in the sinus node of patients with the long QT syndrome. It most likely participates in the important postnatal morphogenesis of the sinus node, AV node, and His bundle. Apoptosis may also participate in the genesis and pathophysiology of cardiomyopathy, paroxysmal arrhythmias, or conduction disturbances (some of which may be responsible for sudden death), focal fibromuscular dysplasia of small coronary arteries, hereditary medial degeneration of the tunica media of coronary arteries, and arrhythmogenic right ventricular dysplasia. The possible role apoptosis in numerous other changes in the human heart, among them the pathogenesis of atherosclerosis and mechanisms of aging in the myocardium, merits future investigation.

The early termination of clinical trials, for either benefit or harm, often generates undue enthusiasm or alarm. The enhanced publicity attending early termination of a trial promotes inappropriate interpretations that are favored by the inherent difficulty of prompt and comprehensive data review. Furthermore, the process of monitoring the accumulating outcome data for early evidence of treatment benefit or harm is fraught with many statistical and methodological difficulties. This report from a task force convened by the Working Group on Arrhythmias of the European Society of Cardiology incorporates first, a series of trials terminated appropriately or inappropriately for benefit or harm and used as examples to illustrate the importance of suitable trial design and of proper stopping rules; second, a description of the committee structure of a clinical trial; third, an analysis of the general design issues; fourth, a review of the main issues in interim analysis with special reference to main strategies for reducing the rate of false-positive claims that could result from early trial termination; and finally, a series of specific recommendations concerning the design, structure, analysis, interpretation, and presentation of a clinical trial.

The compositions of lesion types that precede and that may initiate the development of advanced atherosclerotic lesions are described and the possible mechanisms of their development are reviewed. While advanced lesions involve disorganization of the intima and deformity of the artery, such changes are absent or minimal in their precursors. Advanced lesions are either overtly clinical or they predispose to the complications that cause ischemic episodes; precursors are silent and do not lead directly to complications. The precursors are arranged in a temporal sequence of three characteristic lesion types. Types I and II are generally the only lesion types found in children, although they may also occur in adults. Type I lesions represent the very initial changes and are recognized as an increase in the number of intimal macrophages and the appearance of macrophages filled with lipid droplets (foam cells). Type II lesions include the fatty streak lesion, the first grossly visible lesion, and are characterized by layers of macrophage foam cells and lipid droplets within intimal smooth muscle cells and minimal coarse-grained particles and heterogeneous droplets of extracellular lipid. Type III (intermediate) lesions are the morphological and chemical bridge between type II and advanced lesions. Type III lesions appear in some adaptive intimal thickenings (progression-prone locations) in young adults and are characterized by pools of extracellular lipid in addition to all the components of type II lesions.

Much progress has been made in defining the mechanisms by which altered systolic and diastolic function of the heart may be produced by components of the immune system activated during allograft rejection and myocarditis and in patients with dilated cardiomyopathy. It is clear that injury of the vascular bed can occur via both humoral and cellular mediators and probably accounts for the acute alterations in ventricular compliance that occur during allograft rejection, as well as the accelerated development of graft atherosclerosis. Altered myocyte function and lysis can be produced by CTL in vitro, but the importance of this injury process in vivo remains uncertain. Other cells present in the inflammatory infiltrate can also affect myocyte function and survival. Neutrophils may cause lysis of myocytes, and cytokines produced by infiltrating macrophages and HtL may reach a sufficient concentration in the interstitial microenvironment to decrease myocyte catecholamine responsiveness and/or directly depress myocyte contractility. Humoral antibodies to myocyte cell surface antigens may cause cell damage by an antibody-dependent cytotoxic cell mechanism or by directly binding to and altering sarcolemmal receptor and/or ion channel function. Further elucidation of the extent of involvement of these different mechanisms in specific clinical settings may provide a basis for improved therapy of immune-mediated cardiac injury and dysfunction.

The automatic implantable cardioverter-defibrillator (ICD) is highly effective in reducing sudden death rates in patients with life-threatening ventricular tachyarrhythmias. However, the magnitude of the ability of the ICD to improve overall survival is less certain. Data supporting the contention that the ICD prolongs survival are reviewed. It is evident that the mortality benefit consequent to the marked reduction in sudden death varies widely across subpopulations in a predictable manner. This observation reflects the powerful influence of other clinical factors that constrain survival in typical ICD patients. The implications for future studies on the ICD are discussed.

More than 600,000 children in the United States have a congenital or acquired cardiac abnormality, and millions more are at risk of developing atherosclerotic disease in adulthood, a risk made particularly evident by the prevalence of cardiovascular risk factors in the young. There are barriers to optimum prevention and treatment of these conditions in children and youth. The AHA's Task Force on Children and Youth has described these barriers and outlined a series of recommendations and strategies to meet the challenges they impose. More research is needed, and research initiatives will be developed at scientific conferences designed to review critical areas of cardiac development and etiology of disease in children. Financial support for such research initiatives must be increased. Educational programs on cardiovascular risk factors will be extended to children and their families. When these programs are coordinated with efforts in the community and in schools, they will reduce the prevalence of cardiovascular risk factors. The task force recommends that various departments and committees of the AHA use their resources for the benefit of children: for example, by developing more research initiatives for funding by the AHA or NHLBI and increasing legislative and regulatory efforts in the areas such as mandatory school health programs and tobacco advertising. It is hoped that in the next decade, through research and educational efforts, many advances in the prevention and treatment of cardiovascular diseases in the young will be realized.

Long-term management of patients with Kawasaki disease should be tailored to the degree of coronary arterial involvement. This committee has made recommendations for each risk level about antiplatelet and anticoagulant therapy, physical activity, follow-up assessment by a pediatric cardiologist or primary care physician, and the appropriate diagnostic procedures that may be performed to evaluate cardiac disease. The risk level for a given patient with coronary arterial involvement may change over time because of changes in coronary artery morphology. The recommendations for management presented here are intended as practical interim guidelines until additional prospective or retrospective data are compiled to define more clearly the natural history of Kawasaki disease.

Triaging patients suspected of myocardial infarction is performed primarily in the coronary care unit, with infarction determined within 12 to 24 hours, and only about 20% are subsequently shown to have myocardial infarction. Plasma MB CK is not elevated until 8 to 10 hours after onset, and the ECG is unreliable; thus, the need has arisen for a new "diagnostic mind-set." The need is threefold: (1) more effective triaging in the emergency room to prevent unnecessary use of hospital beds, particularly those in the intensive care units, (2) to administer thrombolytic therapy in the early hours, and (3) earlier detection of coronary reocclusion and reinfarction. Diagnostic imaging techniques such as pyrophosphate, thallium-201 technetium sestamibi, or positron emitting agents lack the necessary early diagnostic specificity, but echocardiography has potential although its specificity is limited. Plasma CK isoforms provide diagnostic sensitivity and specificity of 96% and 94%, respectively, within the initial 4 to 6 hours of onset and can be assayed within minutes. In a prospective study of 1100 patients suspected of infarction, with conventional MB CK, 22% of the patients admitted to the coronary care unit would have had infarction, whereas using the CK isoforms, 75% had infarction and about 50% were discharged home. A scenario for the future might be to initiate thrombolytic therapy outside the hospital (eg, recombinant tissue-type plasminogen activator [r-TPA] 20 mg bolus) and upon arrival, confirm or exclude infarction by the MB CK isoform which can be performed in the emergency room in 20 minutes to determine whether thrombolytic therapy and heparin should be continued.