Atrial fibrillation in the elderly.

Atrial fibrillation is the most common sustained arrhythmia seen in clinical practice. Although it occurs in any age patients, its frequency increases with age and is very common in the elderly. Atrial fibrillation causes substantial symptoms and morbidity and is an important cause of thromboembolism and stroke. The two approaches for therapy in those patients with intermittent or persistent atrial fibrillation are (1) maintenance of sinus rhythm with an antiarrhythmic drug or nonpharmacologic therapy, and (2) maintenance of atrial fibrillation with rate control. At the present time there are no data about the best approach and therapy must therefore be individualized.

Proarrhythmia, a serious complication of antiarrhythmic drugs.

Aggravation of arrhythmia with antiarrhythmic drugs is not an infrequent side effect associated with antiarrhythmic drugs. Defined as the provocation of a new arrhythmia or a significant increase in the frequency of a preexisting arrhythmia, it occurs with all antiarrhythmic agents, although the incidence varies from 6% to 23% with the different drugs. In general, arrhythmia aggravation is an early event, occurring within the first several days of initiating drugs therapy. It has been found, however, that this complication can also occur as a late event, particularly in patients who have evidence of ongoing ischemia that may be overt or silent. Although there is no good way to predict the patient who is likely to experience this complication, it has been observed that there several predictors of an increased risk for experiencing arrhythmia aggravation including significant underlying heart disease, congestive heart failure, evidence of active or potentially active ischemia, and electrolyte abnormalities, particularly hypokalemia.

Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial.

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.

Cost-effectiveness analysis of invasive and noninvasive tests in high risk patients treated with amiodarone after acute myocardial infarction.

OBJECTIVES: We sought to evaluate 1) the cost-effectiveness of amiodarone therapy in postinfarction patients; and 2) the influence of alternative diagnostic strategies (noninvasive only vs. noninvasive and electrophysiologic testing) on survival benefit and cost-effectiveness ratio of amiodarone therapy. BACKGROUND: The cost-effectiveness of amiodarone therapy in postinfarction patients is still unknown, and no study has determined which diagnostic strategy should be used to maximize amiodarone survival benefit while improving its cost-effectiveness ratio. METHODS: We designed a postinfarction scenario wherein heart rate variability analysis on 24-h Holter monitoring was used as a screening test for 2-year amiodarone therapy in a cohort of survivors (mean age 57 years) of a recent myocardial infarction. Three different therapeutic strategies were compared: 1) no amiodarone; 2) amiodarone in patients with depressed heart rate variability; 3) amiodarone in patients with depressed heart rate variability and a positive programmed ventricular stimulation. Total variable costs and quality-adjusted life expectancy during a 20-year period were predicted with use of a Markov simulation model. Costs and charges were calculated with reference to an Italian and American hospital. RESULTS: Amiodarone therapy in patients with depressed heart rate variability and a positive programmed ventricular stimulation was dominated by a blend of the two alternatives. Compared with the no-treatment strategy, the incremental cost-effectiveness ratio of amiodarone therapy in patients with depressed heart rate variability was $10,633 and $39,422 per gained quality-adjusted life-year using Italian costs and American charges, respectively. CONCLUSIONS: Compared with a noninterventional option, amiodarone prescription in all patients with depressed heart rate variability seems to be a more appropriate approach than the alternative based on the combined use of heart rate variability and electrophysiologic study.

Arrhythmias after acute myocardial infarction. Evaluation and management of rhythm and conduction abnormalities.

Patients with myocardial infarction can experience a wide range of arrhythmias and conduction abnormalities, from transient and relatively innocuous sinus bradycardia to life-threatening ventricular fibrillation. This nut-and-bolts article covers all the possibilities, emphasizing the clinical significance of the various arrhythmias and their evaluation and treatment. Also included are indications for temporary and permanent pacemaker placement based on the revised ACC/AHA guidelines.

Regional attitudes of generalists, specialists, and subspecialists about management of atrial fibrillation.

BACKGROUND: It is unknown whether physicians' attitudes about the management of atrial fibrillation (AF) reflect the recommendations of published guidelines. METHODS: To obtain information about physicians' attitudes about management of AF, a questionnaire was returned by 904 (20.1%) of 4500 physicians involved in managing AF (385 cardiologists, 326 internists, and 193 electrophysiologists). The cardiologists and internists were from Massachusetts or California; the electrophysiologists were from around the United States. The questionnaire called for 86 separate answers about use of resources and drug therapy for different types of AF, including recent-onset AF, paroxysmal AF, and chronic AF of less than 6 months' and more than 3 years' duration. RESULTS: Transthoracic echocardiography and thyroid function were requested by more than 90% of physicians; transesophageal echocardiography and catheterization were requested by 10% of physicians. To control ventricular response, digoxin was the overwhelming first-line therapy; calcium channel blockers were favored over beta-blockers for adjunct therapy. To prevent thromboemboli, warfarin sodium was preferred for chronic AF; warfarin or aspirin were equally considered for paroxysmal AF. In considering sinus rhythm, respondents agreed about factors determining whether to revert, the number of drug trials, and the first-line drug choice (quinidine sulfate) but disagreed about second-line antiarrhythmic drugs and whether to hospitalize the patient before initiating drug therapy. CONCLUSIONS: Physicians ranging from primary care providers to subspecialists agree on issues of AF management such as heart rate control and anticoagulation. Attitudes vary widely about issues such as antiarrhythmic drugs.

Should physicians participate in affirming the best approach to atrial fibrillation management?

While all patients with atrial fibrillation should receive anticoagulation and control of ventricular response, it is not clear whether conversion to sinus rhythm is associated with a good long-term outcome. Data are presented detailing current physician practices regarding conversion to sinus rhythm (preferred by 90%) and why participation in the new National Institute of Health trial of atrial fibrillation is desirable.

Safety and tolerability of long-term propafenone therapy for supraventricular tachyarrhythmias. The Propafenone Multicenter Study Group.

An important issue regarding the long-term use of antiarrhythmic drugs concerns the safety of these agents, particularly with regard to cardiac toxicity. Propafenone is an effective drug for preventing supraventricular tachyarrhythmia, but the incidence of side effects during longterm therapy in patients with such arrhythmias has not been adequately reported. A total of 480 patients received oral propafenone as therapy for symptomatic atrial fibrillation, atrial flutter, or supraventricular tachycardia. During the follow-up (mean 14.4 months), 290 patients (60%) discontinued propafenone therapy, but in only 70 patients (15%) was the reason for discontinuation an adverse drug reaction. Overall, 284 patients (59%) experienced at least 1 adverse reaction, and the incidence was related to dose and age >65 years. The overall incidence of side effects was not related to structural heart disease; however, cardiovascular toxicity including arrhythmia aggravation, congestive heart failure, and serious conduction disturbances occurred more often in those with heart disease (20% vs 13%). Sixteen patients died during drug therapy, but in only 1 case was the drug considered contributory. For patients with a supraventricular arrhythmia, propafenone was well tolerated and was infrequently discontinued because of side effects. The incidence of serious cardiac toxicity when propafenone was used to treat supraventricular arrhythmia was low, and these side effects were more frequent in patients with structural heart disease.

Amiodarone: reevaluation of an old drug.

PURPOSE: To review the pharmacology, electrophysiology, and toxicity of amiodarone and to discuss the clinical results produced when amiodarone is used as therapy for patients with atrial fibrillation, patients with nonsustained ventricular tachycardia and cardiomyopathy, patients who have recently had myocardial infarctions, and patients who have survived out-of-hospital cardiac arrest caused by ventricular tachycardia or ventricular fibrillation. DATA SOURCES: Animal and clinical studies involving the pharmacology and electrophysiology of amiodarone and clinical trials in which amiodarone was used as therapy for the arrhythmias noted above were reviewed. STUDY SELECTION: Relevant studies that reported on the efficacy and toxicity of amiodarone and on long-term therapy using amiodarone were reviewed, and their data were summarized. Reports of ongoing trials using amiodarone were also reviewed and summarized. RESULTS: Amiodarone is useful for the treatment of many rhythm disturbances. Although side effects from this agent are common, serious toxicity necessitating discontinuation of therapy is infrequent. Unlike other antiarrhythmic agents, amiodarone has not been shown to increase mortality in any population studied. CONCLUSION: Amiodarone, a unique antiarrhythmic agent with many pharmacologic actions, is effective in the treatment of a wide range of rhythm abnormalities. Several large, randomized trials will provide further information about the clinical usefulness of this agent.

Right coronary artery stenosis: an independent predictor of atrial fibrillation after coronary artery bypass surgery.

OBJECTIVES: This study attempted to determine the importance of severe proximal right coronary artery disease as a predictor of atrial fibrillation in patients after coronary artery bypass surgery. BACKGROUND: Studies in patients undergoing noncardiac surgery have suggested that ischemia in the right coronary artery distribution is associated with a high incidence of atrial fibrillation. However, the importance of right coronary artery disease as a predictor of atrial fibrillation after bypass surgery is unknown. METHODS: The occurrence of sustained postoperative atrial fibrillation was studied prospectively in 168 consecutive patients undergoing coronary artery bypass grafting. Patients were followed up postoperatively until discharge. Severe right coronary artery stenosis was defined as > or = 70% lumen narrowing. RESULTS: Of 104 patients with proximal or mid right coronary artery stenosis, 45 (43%) had atrial fibrillation postoperatively compared with 12 (19%) of the 64 patients without significant right coronary disease (p = 0.001). Univariate predictors of atrial fibrillation included right coronary artery stenosis (p = 0.001), advancing age (p = 0.0001) and lack of beta-adrenergic blocking agent therapy after bypass surgery (p = 0.0004). Multivariate adjusted risk of developing atrial fibrillation after bypass surgery increased with the presence of severe right coronary artery disease (odds ratio 3.69, 95% confidence interval [CI] 1.61 to 8.48), advancing age (odds ratio 2.24/10 years, CI 1.48 to 3.41) and male gender (odds ratio 2.36, CI 1.01 to 5.49). The use of beta-blockers postoperatively was associated with a protective effect (odds ratio 0.4, CI 0.17 to 0.80). CONCLUSIONS: The presence of severe right coronary artery stenosis is an independent and powerful predictor of atrial fibrillation after coronary artery bypass surgery. In association with age, gender and postoperative beta-blocker therapy, these variables can be used to identify patients at increased risk for developing this arrhythmia.

Incidence and significance of ventricular tachycardia and fibrillation in the absence of hypotension or heart failure in acute myocardial infarction treated with recombinant tissue-type plasminogen activator: results from the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial.

OBJECTIVES: The purpose of this study was to determine the incidence of ventricular tachycardia and fibrillation without hypotension or heart failure after treatment with recombinant tissue-type plasminogen activator (rt-PA), anatomic correlates of their development, the effect of immediate intravenous metoprolol on their occurrence and the outcome of patients with these arrhythmias. BACKGROUND: Malignant arrhythmias after thrombolytic therapy have been reported to occur as a result of coronary reperfusion, which is associated with reduced mortality in patients receiving thrombolytic therapy. METHODS: We analyzed data from 2,546 patients in the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial without congestive heart failure or hypotension during the 1st 24 h after study entry. Forty-nine patients (1.9%) developed sustained ventricular tachycardia or ventricular fibrillation within 24 h of study entry (group 1), and 2,497 patients (98.1%) did not (group 2). RESULTS: Baseline characteristics and admission laboratory values were similar in the two groups. In patients undergoing protocol angiography 18 to 48 h after rt-PA, the infarct-related artery was patient in a greater percent of group 2 patients (87% [1,015 of 1,169]) than group 1 patients (68% [15 of 22], p = 0.01), although angiography was performed less frequently in group 1 than in group 2. More group 1 than group 2 patients died within 21 days (20.4%) (1.6%, p < 0.001). For patients surviving to 21 days, there was no difference in mortality between patients in the two groups in the following year. CONCLUSIONS: Ventricular tachycardia and fibrillation are not markers for reperfusion after thrombolytic therapy. These arrhythmias are associated with occlusion, not patency, of the infarct-related artery. Early mortality is increased in patients who develop ventricular tachycardia and fibrillation, even in the absence of congestive heart failure and hypotension.

Aggravation of arrhythmia: a complication of antiarrhythmic drugs.

Aggravation of arrhythmia, defined as worsening of a preexisting arrhythmia or the occurrence of a new arrhythmia, is a common complication of antiarrhythmic drug therapy. Although it is largely an unpredictable event, patients at greatest risk are those with a history of congestive heart failure due to systolic dysfunction who present with a sustained ventricular tachyarrhythmia. As a rule, aggravation of arrhythmia is an early event, occurring within the first few days of initiating therapy. However, in the Cardiac Arrhythmia Suppression Trial (CAST), the increased sudden death mortality due to drug therapy, which was a result of arrhythmia aggravation, occurred throughout the entire duration of the trial, suggesting that arrhythmia aggravation can also be a late complication of therapy. Also disturbing was the fact that patients in CAST were low risk and did not have congestive heart failure or a serious ventricular tachyarrhythmia. This suggests that another important risk factor is myocardial ischemia and its potentially dangerous interaction with antiarrhythmic drugs. In patients with heart disease, especially those with coronary artery disease, antiarrhythmic drugs must therefore be used cautiously. Close and continuous follow-up is mandatory.

Class 1 antiarrhythmic agents for therapy of atrial fibrillation.

Atrial fibrillation is most the common sustained arrhythmia seen by the cardiologist. Therapy to prevent this arrhythmia is often prescribed so as to eliminate associated symptoms which include palpitations, fatigue, dizziness and presyncope, shortness of breath, congestive heart failure and emboli, especially those that result in a cerebrovascular accident. Pharmacologic therapy is the only effective therapy for preventing atrial fibrillation and the class 1 antiarrhythmic drugs remain the most frequently used agents. Although each of these agents has been reported to be effective for preventing atrial fibrillation, they are associated with frequent side effects, some of which are potentially serious, especially aggravation of arrhythmia. Prior to treatment the benefit vs risk of these drugs for each patient must be established.

Pharmacoeconomic considerations in antiarrhythmic therapy.

Recently, the Cardiac Arrhythmia Suppression Trial (CAST) has focused attention on the morbidity and mortality that may be associated with pharmacological antiarrhythmic therapies. While the severity and frequency of adverse effects vary among the available agents, it is uncertain whether initial therapy with one agent is preferable to that with another when efficacy, incidence of adverse effects and costs of treating these adverse effects are examined. Moreover, it is uncertain whether pharmacotherapy is more cost-effective than other strategies.

Evaluating patients with ventricular arrhythmia. Role of the signal-averaged electrocardiogram, exercise test, ambulatory electrocardiogram, and electrophysiologic studies.

There are several methods available for the evaluation of patients with ventricular arrhythmia. The most effective approaches, however, involve the use of techniques that provide objective data. These include ambulatory monitoring and exercise testing (a noninvasive approach), and electrophysiologic testing (invasive). The information derived from these two approaches is complementary, and both are important for patient evaluation and management. These methods are useful for establishing the risk of arrhythmia occurrence in certain patient groups and for establishing the effect of antiarrhythmic agents. The signal-averaged ECG is of help in establishing risk in some patient groups, but it has no role for evaluating drug therapy.

Ventricular arrhythmia in congestive heart failure.

The importance of ventricular arrhythmia is based on its association with sudden death. In certain groups of patients, ventricular arrhythmia--primarily runs of nonsustained ventricular tachycardia (NSVT)--is associated with an increased risk for sudden death. Although this relationship has been most often reported in patients with recent myocardial infarction, it has also been recognized in patients with dilated cardiomyopathy, regardless of etiology. Therefore, ventricular arrhythmia is common in patients with CHF due to cardiomyopathy. A number of studies have reported that 70-95% of patients with cardiomyopathy and congestive heart failure (CHF) have frequent ventricular premature beats, and 40-80% will manifest runs of NSVT. Many factors are responsible for ventricular arrhythmia in such patients, including structural abnormalities, electrolyte imbalance, hemodynamic impairment, activation of neurohormonal mechanisms, and pharmacologic therapy. Many studies have reported a high yearly mortality in patients with cardiomyopathy and CHF; greater than 40% of deaths are sudden, most often the result of sustained ventricular tachyarrhythmia. Most studies have noted an association between presence (and frequency) of NSVT and risk of sudden cardiac death in these patients. Unfortunately, other techniques--such as the signal-averaged electrocardiogram and electrophysiologic testing--are not helpful in identifying the individual at risk. Although several drug interventions will reduce mortality from progressive CHF, these drugs have not been shown to reduce sudden death and, indeed, have a variable effect on ventricular arrhythmia. Although NSVT is a marker for increased risk for sudden death, it is uncertain if antiarrhythmic drugs will prevent this outcome. Antiarrhythmic drugs have not been shown to be effective for preventing sudden death, although there are as yet no well-controlled randomized trials. Several studies suggest that amiodarone and beta blockers are beneficial, but this requires confirmation. For patients who have been resuscitated following an episode of sudden death due to a sustained ventricular tachyarrhythmia, antiarrhythmic therapy guided by invasive and noninvasive techniques appears to reduce risk of recurrent arrhythmia. However, the response rate to antiarrhythmic agents is low and side effects are common in patients with CHF. Especially important is the increased risk of precipitating CHF and aggravating the arrhythmia being treated. For many such patients who have had serious ventricular tachyarrhythmia, the automatic implantable cardioverter defibrillator may prove a better option. Other drugs used for management of CHF reduce overall mortality, but not risk of sudden death.

Therapy with and assessment of class III antiarrhythmic agents in different patient populations.

The present article reviews the therapeutic efficacy of class III antiarrhythmic agents, particularly amiodarone, in patients with atrial and ventricular arrhythmias in the setting of different cardiac disorders. Both Holter monitoring and electrophysiologic studies appear to constitute reliable methods for evaluating the effects of class III agents and the long-term outcome in patients with a history of sustained ventricular tachycardia or fibrillation. The efficacy and tolerance of amiodarone in different patient populations is discussed.