Life-threatening ventricular arrhythmias due to transient or correctable causes: high risk for death in follow-up.

OBJECTIVES: This study evaluated the prognosis of patients resuscitated from ventricular tachycardia (VT) or ventricular fibrillation (VF) with a transient or correctable cause suspected as the cause of the VT/VF. BACKGROUND: Patients resuscitated from VT/VF in whom a transient or correctable cause has been identified are thought to be at low risk for recurrence and often receive no primary treatment for their arrhythmias. METHODS: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, patients with a potentially transient or correctable cause of VT/VF were not eligible for randomization. The mortality of these patients was compared with the mortality of patients with a known high risk of recurrence of VT/VF in the AVID registry. RESULTS: Compared with patients having high risk VT/VF, those with a transient or correctable cause for their presenting VT/VF were younger and had a higher left ventricular ejection fraction. These patients were more often treated with revascularization as the primary therapy, more commonly received a beta-blocker, less often required therapy for congestive heart failure and less commonly received either an antiarrhythmic drug or an implantable cardioverter defibrillator. Nevertheless, subsequent mortality of patients with a transient or correctable cause of VT/VF was no different or perhaps even worse than that of the primary VT/VF population. CONCLUSIONS: Patients identified with a transient or correctable cause for their VT/VF remain at high risk for death. Further research is needed to define truly reversible causes of VT/VF. Meanwhile, these patients may require more aggressive evaluation, treatment and follow-up than is currently practiced.

Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study.

BACKGROUND: This double-blind, multicenter, placebo-controlled study determined the efficacy and safety of dofetilide in converting atrial fibrillation (AF) or atrial flutter (AFl) to sinus rhythm (SR) and maintaining SR for 1 year. METHODS AND RESULTS: Patients with AF or AFl (n=325) were randomized to 125, 250, or 500 microgram dofetilide or placebo twice daily. Dosages were adjusted for QTc response and, after 105 patients were enrolled, for calculated creatinine clearance (Cl(Cr)). Pharmacological cardioversion rates for 125, 250, and 500 microgram dofetilide were 6.1%, 9.8%, and 29.9%, respectively, versus 1.2% for placebo (250 and 500 microgram versus placebo; P=0.015 and P<0.001, respectively). Seventy percent of pharmacological cardioversions with dofetilide were achieved in 24 hours and 91% in 36 hours. For the 250 patients who successfully cardioverted pharmacologically or electrically, the probability of remaining in SR at 1 year was 0.40, 0.37, 0.58 for 125, 250, and 500 microgram dofetilide, respectively, and 0.25 for placebo (500 microgram versus placebo, P=0.001). Two cases of torsade de pointes occurred, 1 on day 2 and the other on day 3 (0.8% of all patients given active drug); 1 sudden cardiac death, classified as proarrhythmic, occurred on day 8 (0.4% of all patients given active drug). CONCLUSIONS: Dofetilide, a new class III antiarrhythmic agent, is moderately effective in cardioverting AF or AFl to SR and significantly effective in maintaining SR for 1 year. In-hospital initiation and dosage adjustment based on QTc and Cl(Cr) are necessary to minimize a small but nonnegligible proarrhythmic risk.

Relative effectiveness of the implantable cardioverter-defibrillator and antiarrhythmic drugs in patients with varying degrees of left ventricular dysfunction who have survived malignant ventricular arrhythmias. AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators.

OBJECTIVES: We sought to assess the effect of baseline ejection fraction on survival difference between patients with life-threatening ventricular arrhythmias who were treated with an antiarrhythmic drug (AAD) or implantable cardioverter-defibrillator (ICD). BACKGROUND: The Antiarrhythmics Versus Implantable Defibrillators (AVID) study demonstrated improved survival in patients with ventricular fibrillation or ventricular tachycardia with a left ventricular ejection fraction (LVEF) < or =0.40 or hemodynamic compromise. METHODS: Survival differences between AAD-treated and ICD-treated patients entered into the AVID study (patients presenting with sustained ventricular arrhythmia associated with an LVEF < or =0.40 or hemodynamic compromise) were compared at different levels of ejection fraction. RESULTS: In patients with an LVEF > or =0.35, there was no difference in survival between AAD-treated and ICD-treated patients. A test for interaction was not significant, but had low power to detect an interaction. For patients with an LVEF 0.20 to 0.34, there was a significantly improved survival with ICD as compared with AAD therapy. In the smaller subgroup with an LVEF <0.20, the same magnitude of survival difference was seen as that in the 0.20 to 0.34 LVEF subgroup, but the difference did not reach statistical significance. CONCLUSIONS: These data suggest that patients with relatively well-preserved LVEF (> or =0.35) may not have better survival when treated with the ICD as compared with AADs. At a lower LVEF, the ICD appears to offer improved survival as compared with AADs. Prospective studies with larger patient numbers are needed to assess the effect of relatively well-preserved ejection fraction (> or =0.35) on the relative treatment effect of AADs and the ICDs.

Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial.

OBJECTIVES: To evaluate whether use of beta-adrenergic blocking agents, alone or in combination with specific antiarrhythmic therapy, is associated with improved survival in persons with ventricular fibrillation (VF) or symptomatic ventricular tachycardia (VT). BACKGROUND: The ability of beta-blockers to alter the mortality of patients with VF or VT receiving contemporary medical management is not well defined. METHODS: Survival of 1,016 randomized and 2,101 eligible, nonrandomized patients with VF or symptomatic VT followed in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial through December 31, 1996 was assessed using Cox proportional hazards analysis. RESULTS: The 817 (28%) patients discharged from hospital receiving beta-blockers had less ventricular dysfunction, fewer symptoms of heart failure and a different pattern of medication use compared with patients not receiving beta-blockers. Before adjustment for important prognostic variables, beta-blockade was not significantly associated with survival in randomized or in eligible, nonrandomized patients treated with specific antiarrhythmic therapy. After adjustment, beta-blockade remained unrelated to survival in randomized or in eligible, nonrandomized patients treated with amiodarone alone (n = 1142; adjusted relative risk [RR] = 0.96; 95% confidence interval [CI] 0.64-1.45; p = 0.85) or a defibrillator alone (n = 1347; adjusted RR = 0.88; 95% CI 0.55 to 1.40; p = 0.58). In contrast, beta-blockade was independently associated with improved survival in eligible, nonrandomized patients who were not treated with specific antiarrhythmic therapy (n = 412; adjusted RR = 0.47; 95% CI 0.25 to 0.88; p = 0.018). CONCLUSIONS: Beta-blocker use was independently associated with improved survival in patients with VF or symptomatic VT who were not treated with specific antiarrhythmic therapy, but a protective effect was not prominent in patients already receiving amiodarone or a defibrillator.

Near doubling of heart rate after intravenous verapamil for treatment of atrial fibrillation without preexcitation.

Initial treatment of atrial fibrillation often involves pharmacological therapy to control ventricular response. While verapamil is usually safe and effective when used for this purpose, we report a proarrhythmic response. In this report a 30-year-old female presented with palpitations associated with atrial fibrillation and a ventricular response of 145 beats/min. Soon after she was given 5 mg of intravenous verapamil her ECG documented a regular wide QRS tachycardia at 290 beats/min. After 7 seconds the rhythm returned to an irregularly irregular narrow QRS tachycardia at 125-150 beats/min. At a later electrophysiology study there was neither evidence of preexcitation nor inducible supraventricular or ventricular tachycardia. These data suggest that verapamil may have been associated with acceleration of the heart rate. The mechanism of proarrhythmia may be related to an alteration in the atrial rhythm from atrial fibrillation to atrial flutter, with additional factors as well.

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.

Significance of magnesium in congestive heart failure.

Electrolyte balance has been regarded as a factor important to cardiovascular stability, particularly in congestive heart failure. Among the common electrolytes, the significance of magnesium has been debated because of difficulty in accurate measurement and other associated factors, including other electrolyte abnormalities. The serum magnesium level represents < 1% of total body stores and does not reflect total-body magnesium concentration, a clinical situation very similar to that of serum potassium. Magnesium is important as a cofactor in several enzymatic reactions contributing to stable cardiovascular hemodynamics and electrophysiologic functioning. Its deficiency is common and can be associated with risk factors and complications of heart failure. Typical therapy for heart failure (digoxin, diuretic agents, and ACE inhibitors) are influenced by or associated with significant alteration in magnesium balance. Magnesium therapy, both for deficiency replacement and in higher pharmacologic doses, has been beneficial in improving hemodynamics and in treating arrhythmias. Magnesium toxicity rarely occurs except in patients with renal dysfunction. In conclusion, the intricate role of magnesium on a biochemical and cellular level in cardiac cells is crucial in maintaining stable cardiovascular hemodynamics and electrophysiologic function. In patients with congestive heart failure, the presence of adequate total-body magnesium stores serve as an important prognostic indicator because of an amelioration of arrhythmias, digitalis toxicity, and hemodynamic abnormalities.

Clinical assessment of adrenergic tone and responsiveness to beta-blocker therapy in patients with symptomatic ventricular tachycardia and no apparent structural heart disease.

To further define the relation between changing adrenergic tone, beta-blocker therapy, and clinical ventricular tachycardia (VT), we evaluated these factors in 35 patients with VT unrelated to coronary artery disease or ventricular dysfunction. Testing included Holter monitoring (91% had VT), exercise test (69% had VT), Adrenergic responsiveness of VT was graded according to diurnal variation, response to exercise, isoproterenol infusion, and response to beta-blockers. beta-Blockers were effective and well tolerated in this population. There was also a predictable relation between changing adrenergic tone and the arrhythmia response to beta-blocker therapy.

Is the time domain signal-averaged electrocardiogram helpful in patients with ventricular tachycardia without apparent structural heart disease?

The signal-average electrocardiogram (SAECG) has been a screening method for identifying patients at risk for ventricular tachycardia (VT) in the setting of coronary artery disease (CAD). Its significance in patients with VT unrelated to CAD or left ventricular dysfunction is undetermined. In order to define the value of SAECG in this patient population further, we compared the time domain SAECG at 25, 40, and 80 Hz filters in 35 patients with clinically symptomatic VT in the absence of structural heart disease was compared with 10 normal controls and 10 patients with CAD and inducible VT. SAECG data in patients without structural heart disease were intermediate between normal controls and patients with CAD. No single or combined SAECG criterion helped to differentiate between patients with inducible and noninducible VT. There was no concordance to other arrhythmia testing. It was concluded that signal-averaged electrocardiography may have little screening value in VT unrelated to CAD or left ventricular dysfunction.

Life-threatening alterations in heart rate after the use of adenosine in atrial flutter.

Adenosine has become the preferred treatment for common types of supraventricular tachycardia because it is extremely effective and rarely associated with with serious side effects. It has also been advocated as an intervention for diagnostic use to assess uncommon types of tachycardia. Evidence is shown in this report that adenosine was associated with dangerous worsening of arrhythmia in patients with atrial flutter. In two patients, adenosine precipitated acceleration of ventricular response, in one case necessitating emergent cardioversion. Both patients had atrial flutter with 2 to 1 atrioventricular block that evolved into 1 to 1 atrioventricular conduction. In three other patients, adenosine was associated with prolonged bradyasystole and hypotension. In each of the five patients, adenosine was given in a standard fashion (6 or 12 mg). In summary, adenosine should be recognized as a potentially dangerous intervention in patients with atrial flutter. If it is used for diagnostic purposes, resuscitative equipment should be readily available.

A review of magnesium, acute myocardial infarction and arrhythmia.

Many years ago, experimental medicine accumulated substantial evidence that magnesium (Mg) balance was important for a stable cardiovascular system. Recent clinical interest was aroused by evidence of decreased mortality in patients with acute myocardial infarction (AMI), treated with Mg infusions. Pharmacologic actions of Mg include its antiarrhythmic, antivasospastic and other important cardiovascular effects, substantiating the rationale for its use in AMI. Direct pharmacologic effect of this ion, rather than compensation of hypomagnesemia frequently encountered during acute ischemic injury, has been suggested to account for the above benefits. Several trials studied the efficacy of early Mg therapy in decreasing mortality from AMI while most of the data point to improved survival, a few trials could not demonstrate any benefit of Mg. The reported rate of complications with this therapy is low though the potential for serious side effects exists. Larger studies of Mg in AMI are expected to resolve the existing controversy.

Spectrum of right heart involvement in patients with ventricular tachycardia unrelated to coronary artery disease or left ventricular dysfunction.

We studied 41 patients with clinically symptomatic ventricular tachycardia in the absence of coronary artery disease or left ventricular dysfunction to define the extent of right and left heart derangement and their relation to electrophysiologic and clinical data. Individual echocardiographic measurements as well as global assessment scores of the right and left heart demonstrated a wide spectrum of right heart echocardiographic abnormalities. There was much less variation in the left heart, with the majority of patients being close to normal. There was an association between the right heart score, the clinical presentation of arrhythmia, the response to programmed electrical stimulation, and the recurrence of arrhythmia (p < 0.05). Thus echocardiographic findings demonstrate the whole spectrum of right heart involvement in patients with apparent idiopathic ventricular tachycardia and can give insight into clinical history, arrhythmia inducibility, and prognosis.