Bradycardic syncope in 2 patients who recently began gatifloxacin treatment.

Gatifloxacin is a synthetic broad-spectrum 8-methoxyfluoroquinolone approved by the United States Food and Drug Administration in December 1999. Few side effects of this new antibiotic have been reported, and there are no previous case reports of bradyarrhythmias. We report 2 cases of syncope due to bradycardia in patients who recently began treatment with gatifloxacin.

Differences in inducibility and prognosis of in-hospital versus out-of-hospital identified nonsustained ventricular tachycardia in patients with coronary artery disease: clinical and trial design implications.

OBJECTIVES: The goal of this study was to describe the influence of the clinical setting (in-hospital vs. out-of-hospital) in which nonsustained ventricular tachycardia (NSVT) is discovered on the rate of inducibility of sustained ventricular tachycardia (VT), arrhythmic events and survival in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. BACKGROUND: In-hospital presentation of sustained VT is independently associated with lower long-term overall survival. The impact of the clinical setting in which NSVT is documented is unknown. METHODS: In the Multicenter Unsustained Tachycardia Trial (MUSTT), designed to assess the benefit of randomized antiarrhythmic therapy guided by electrophysiologic testing in patients with asymptomatic NSVT, CAD and LV dysfunction, eligible patients were enrolled irrespective of the setting in which the index arrhythmia was discovered. In this retrospective analysis, we compared the rate of VT inducibility and outcome of MUSTT-enrolled patients with in-hospital versus out-of-hospital presentation of NSVT. RESULTS: Monomorphic sustained VT was induced in 35% and 28% of the patients whose index NSVT occurred in-hospital and out-of-hospital, respectively (adjusted p = 0.006). Cardiac arrest or death due to arrhythmia at two- and five-year follow-ups were 14% and 28% for untreated patients with in-hospital-identified NSVT and 11% and 21% for the out-of-hospital group (adjusted p = 0.10). Overall mortality rates at two- and five-year follow-ups were 24% and 48% for inpatients and 18% and 38% for outpatients (adjusted p = 0.018). In patients randomized to antiarrhythmic therapy, there was no significant interaction between patient status (in-hospital vs. out-of-hospital) and treatment impact on the rates of total mortality (p = 0.98) and arrhythmic events (p = 0.08). CONCLUSIONS: In patients with CAD and impaired LV function, asymptomatic NSVT identified in-hospital, compared with that identified out-of-hospital, is associated with a higher rate of induction of sustained VT and overall mortality. Therefore, in similar patients, the clinical setting in which NSVT is discovered should be taken into account when formulating patient risk, treatment and clinical trial design.

Antiarrhythmic drug therapy in the Multicenter UnSustained Tachycardia Trial (MUSTT): drug testing and as-treated analysis.

OBJECTIVES: Using data from the Multicenter UnSustained Tachycardia Trial (MUSTT), we examined the factors used to select antiarrhythmic drug therapy and their impact on outcomes. BACKGROUND: The MUSTT examined the use of programmed ventricular stimulation (PVS) to guide antiarrhythmic therapy in patients with coronary arteriosclerosis, left ventricular dysfunction and asymptomatic, unsustained ventricular tachycardia (VT). Trial outcomes may reflect factors used to select antiarrhythmic drug therapy. METHODS: We compared subgroups of patients with inducible sustained VT randomized to PVS-guided antiarrhythmic therapy (n = 351), in particular those receiving PVS-guided antiarrhythmic drug therapy (n = 142) versus no antiarrhythmic therapy (controls, n = 353). RESULTS: "Effective" antiarrhythmic drug therapy (i.e., the term "effective" was used to denote therapy that resulted in noninducible VT or hemodynamically stable induced VT) was found for 142 of the 351 patients (43%), most often at the first or second PVS session (125/142, 88%). Mortality among the 142 patients did not differ from that among control patients. Of these 142 patients, the PVS end point was noninducibility in 91 patients and stable VT in 51 patients. Mortality did not differ between these two groups either, but arrhythmia was numerically more frequent in the PVS-induced stable VT group. Mortality was greatest in the few patients receiving propafenone (unadjusted p = 0.07, adjusted p = 0.14 vs. controls), but mortality with all agents did not differ from that of controls, even after adjustment. CONCLUSIONS: Even when presenting the results as favorably as possible, we found no benefit with PVS-guided drug therapy in patients with clinical unsustained VT who had inducible sustained VT. These findings are unaltered by using different end points for PVS or considering the response to individual drugs.

Prediction of long-term outcomes by signal-averaged electrocardiography in patients with unsustained ventricular tachycardia, coronary artery disease, and left ventricular dysfunction.

BACKGROUND: An abnormal signal-averaged ECG (SAECG) is a noninvasive marker of the substrate of sustained ventricular tachycardia after myocardial infarction. We assessed its prognostic ability in patients with asymptomatic unsustained ventricular tachycardia, coronary artery disease, and left ventricular dysfunction. METHODS AND RESULTS: A blinded core laboratory analyzed SAECG tracings from 1925 patients in a multicenter trial. Cox proportional hazards modeling was used to examine individual and joint relations between SAECG variables and arrhythmic death or cardiac arrest (primary end point), cardiac death, and total mortality. We also assessed the prognostic utility of SAECG at different levels of ejection fraction (EF). A filtered QRS duration >114 ms (abnormal SAECG) independently predicted the primary end point and cardiac death, independent of clinical variables, cardioverter-defibrillator implantation, and antiarrhythmic drug therapy. With an abnormal SAECG, the 5-year rates of the primary end point (28% versus 17%, P=0.0001), cardiac death (37% versus 25%, P=0.0001), and total mortality (43% versus 35%, P=0.0001) were significantly higher. The combination of EF <30% and abnormal SAECG identified a particularly high-risk subset that constituted 21% of the total population. Thirty-six percent and 44% of patients with this combination succumbed to arrhythmic and cardiac death, respectively. CONCLUSIONS: SAECG is a powerful predictor of poor outcomes in this population. The noninvasive combination of an abnormal SAECG and reduced EF may have utility in selecting high-risk patients for intervention.

Current approaches to evaluation and management of patients with ventricular arrhythmias.

The clinical manifestations of ventricular arrhythmias encompass a broad spectrum, from complete absence of symptoms to sudden death. Although our understanding of the pathophysiology and natural history of these arrhythmias has advanced significantly over the past decade, large gaps in our knowledge remain, especially in patients with heart failure not due to coronary artery disease. We have learned much about the appropriate roles of antiarrhythmic drugs and implantable defibrillators in the prevention of sudden death. Studies performed over the past decade have made clear that the primary treatment for patients at high risk for life-threatening ventricular arrhythmias should be the implantable defibrillator. However, specific syndromes causing ventricular tachyarrhythmias are being recognized, and care must be individualized. Although hospital mortality from acute myocardial infarction has decreased as a result of newer therapies, sudden death after hospital discharge remains an important problem, causing at least 30% of post-infarction deaths, even in patients who have received thrombolytic therapy. Two independent studies have confirmed that patients with asymptomatic non-sustained ventricular tachycardia in the presence of left ventricular ejection fraction < .40 after myocardial infarction who have sustained ventricular tachycardia inducible by electrophysiologic study are at significant risk for sudden death. This risk is significantly reduced by ICD, but not pharmacologic, antiarrhythmic therapy. Our major challenge at this time is not how best to treat high risk patients, but how best to identify them prior to events. Finally, physicians should be aware that many symptomatic ventricular tachycardias are now curable at low risk, using catheters to deliver radiofrequency energy.

Nonsustained ventricular tachycardia. A guide to the clinical significance and management.

The patient with nonsustained ventricular tachycardia represents a common management problem for the cardiologists and internists. Treatment is sometimes needed for the suppression of symptoms. More commonly, nonsustained ventricular tachycardia is asymptomatic, and the clinician must determine the prognostic importance. The prognostic implications, the role of electrophysiologic study, and the potential role of pharmacologic and defibrillator intervention depend on the underlying cardiac substrate present in the individual patient.

Electrophysiologic and clinical effects of angiotensin-converting enzyme inhibitors in patients with prior myocardial infarction, nonsustained ventricular tachycardia, and depressed left ventricular function. MUSTT Investigators. Multicenter UnSustained Tachycardia Trial.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce sudden cardiac death and all-cause mortality. They also may have direct antiarrhythmic properties. We retrospectively analyzed the data from the Multicenter UnSustained Tachycardia Trial (MUSTT), to determine the effects of ACE inhibitors on inducibility of sustained ventricular tachycardia and on sudden cardiac death and overall mortality in 2,087 patients with prior myocardial infarction, nonsustained ventricular tachycardia, and depressed left ventricular function. Results of electrophysiologic testing were compared by use of ACE inhibitors at baseline, and outcomes were compared between the 564 patients prescribed ACE inhibitors at discharge and the 1,523 patients who did not receive treatment. The inducibility of sustained ventricular tachycardia during electrophysiologic testing did not differ by baseline ACE inhibitor use (unadjusted p = 0.75). Patients discharged from hospital on ACE inhibitors had a lower ejection fraction, more extensive coronary artery disease, and fewer previous revascularizations at baseline. After adjustments for differences in baseline factors and initial hospitalization variables, there were no significant differences in total mortality (p = 0.47) or arrhythmic death or cardiac arrest (p = 0.51) with ACE inhibitor use at discharge over a median 43 months of follow-up.

The role of the implantable cardioverter-defibrillator for prevention of sudden cardiac death.

Sudden cardiac death, which accounts for approximately 350,000 deaths each year, is a major health care problem. Antiarrhythmic drugs have not been reliable in preventing sudden cardiac death. Although beta-blockers, angiotensin-converting enzyme inhibitors, and revascularization play a role in prevention of sudden cardiac death, the development and subsequent refinement of the implantable cardioverter-defibrillator has made the most important contribution to its management. Several randomized, controlled trials have demonstrated improved survival in patients resuscitated from cardiac arrest. Two recent trials also suggest a role for primary prevention in selected patients with coronary artery disease, ventricular dysfunction, and nonsustained ventricular tachycardia in whom sustained ventricular tachycardia is induced. Further technological refinements and development of new, more sensitive risk stratifiers with a higher positive predictive value for sudden cardiac death will expand the indications for this life-saving therapy.

Nonsustained ventricular tachycardia.

The patient with nonsustained ventricular tachycardia represents a common management problem for the cardiologist. The challenges posed by this type of arrhythmia differs from those posed by other arrhythmias, because most instances of nonsustained ventricular tachycardia do not cause symptoms. This article reviews common situations in which nonsustained ventricular tachycardia occurs and their appropriate management.

Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators.

BACKGROUND: The mortality rate among patients with coronary artery disease, abnormal ventricular function, and unsustained ventricular tachycardia is high. The usefulness of electrophysiologic testing for risk stratification in these patients is unclear. METHODS: We performed electrophysiologic testing in patients who had coronary artery disease, a left ventricular ejection fraction of 40 percent or less, and asymptomatic, unsustained ventricular tachycardia. Patients in whom sustained ventricular tachyarrhythmias could be induced were randomly assigned to receive either antiarrhythmic therapy guided by electrophysiologic testing or no antiarrhythmic therapy. The primary end point was cardiac arrest or death from arrhythmia. Patients without inducible tachyarrhythmias were followed in a registry. We compared the outcomes of 1397 patients in the registry with those of 353 patients with inducible tachyarrhythmias who were randomly assigned to receive no antiarrhythmic therapy in order to assess the prognostic value of electrophysiologic testing. RESULTS: Patients were followed for a median of 39 months. In a Kaplan-Meier analysis, two-year and five-year rates of cardiac arrest or death due to arrhythmia were 12 and 24 percent, respectively, among the patients in the registry, as compared with 18 and 32 percent among the patients with inducible tachyarrhythmias who were assigned to no antiarrhythmic therapy (adjusted P<0.001). Overall mortality after five years was 48 percent among the patients with inducible tachyarrhythmias, as compared with 44 percent among the patients in the registry (adjusted P=0.005). Deaths among patients without inducible tachyarrhythmias were less likely to be classified as due to arrhythmia than those among patients with inducible tachyarrhythmias (45 and 54 percent, respectively; P=0.06). CONCLUSIONS: Patients with coronary artery disease, left ventricular dysfunction, and asymptomatic, unsustained ventricular tachycardia in whom sustained ventricular tachyarrhythmias cannot be induced have a significantly lower risk of sudden death or cardiac arrest and lower overall mortality than similar patients with inducible sustained tachyarrhythmias.

A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators.

BACKGROUND: Empirical antiarrhythmic therapy has not reduced mortality among patients with coronary artery disease and asymptomatic ventricular arrhythmias. Previous studies have suggested that antiarrhythmic therapy guided by electrophysiologic testing might reduce the risk of sudden death. METHODS: We conducted a randomized, controlled trial to test the hypothesis that electrophysiologically guided antiarrhythmic therapy would reduce the risk of sudden death among patients with coronary artery disease, a left ventricular ejection fraction of 40 percent or less, and asymptomatic, unsustained ventricular tachycardia. Patients in whom sustained ventricular tachyarrhythmias were induced by programmed stimulation were randomly assigned to receive either antiarrhythmic therapy, including drugs and implantable defibrillators, as indicated by the results of electrophysiologic testing, or no antiarrhythmic therapy. Angiotensin-converting-enzyme inhibitors and beta-adrenergic-blocking agents were administered if the patients could tolerate them. RESULTS: A total of 704 patients with inducible, sustained ventricular tachyarrhythmias were randomly assigned to treatment groups. Five-year Kaplan-Meier estimates of the incidence of the primary end point of cardiac arrest or death from arrhythmia were 25 percent among those receiving electrophysiologically guided therapy and 32 percent among the patients assigned to no antiarrhythmic therapy (relative risk, 0.73; 95 percent confidence interval, 0.53 to 0.99), representing a reduction in risk of 27 percent). The five-year estimates of overall mortality were 42 percent and 48 percent, respectively (relative risk, 0.80; 95 percent confidence interval, 0.64 to 1.01). The risk of cardiac arrest or death from arrhythmia among the patients who received treatment with defibrillators was significantly lower than that among the patients discharged without receiving defibrillator treatment (relative risk, 0.24; 95 percent confidence interval, 0.13 to 0.45; P<0.001). Neither the rate of cardiac arrest or death from arrhythmia nor the overall mortality rate was lower among the patients assigned to electrophysiologically guided therapy and treated with antiarrhythmic drugs than among the patients assigned to no antiarrhythmic therapy. CONCLUSIONS: Electrophysiologically guided antiarrhythmic therapy with implantable defibrillators, but not with antiarrhythmic drugs, reduces the risk of sudden death in high-risk patients with coronary disease.

Prediction of sustained ventricular tachycardia inducible by programmed stimulation in patients with coronary artery disease. Utility of clinical variables.

BACKGROUND: Cardiologists often use clinical variables to determine the need for electrophysiological studies to stratify patients for risk of sudden death. It is not clear whether this is rational in patients with coronary artery disease, left ventricular dysfunction, and nonsustained ventricular tachycardia. METHODS AND RESULTS: We analyzed the first 1721 patients enrolled in the Multicenter UnSustained Tachycardia Trial to determine whether clinical variables could predict which patients would have inducible sustained monomorphic ventricular tachycardia. The rate of inducibility of sustained ventricular tachycardia was significantly higher in patients with a history of myocardial infarction and in men compared with women. There was a progressively increased rate of inducibility with increasing numbers of diseased coronary arteries. There was a significantly lower rate of inducibility in patients with prior coronary artery bypass surgery and in patients who also had noncoronary cardiac disease. The rate of inducibility was higher in patients of white race, patients with recent (

Idiopathic ventricular tachycardia.

Most ventricular tachycardias encountered in clinical practice occur in patients who have structural heart disease. Idiopathic ventricular tachycardia refers to those arrhythmias that occur in patients without structural heart disease, metabolic/electrolyte abnormalities, or the long QT syndrome. Three commonly recognized forms of idiopathic ventricular tachycardia include: (a) ventricular tachycardia associated with mitral valve prolapse, (b) ventricular tachycardia originating from the right ventricular outflow tract, and (c) ventricular tachycardia originating from the left ventricle. Recently, a fourth type of idiopathic ventricular tachycardia, termed the Brugada syndrome, has been identified as responsible for some cases of cardiac arrest in persons without apparent structural heart disease. Each form of ventricular tachycardia may be considered a discrete syndrome based on its electrocardiographic characteristics, mechanisms, responses to pharmacologic intervention, and prognosis (good in most cases). Ventricular tachycardias range from the common to the exotic, but all represent syndromes with which the internist and general cardiologist should be familiar.

Radiofrequency catheter ablation of postinfarction ventricular tachycardia: long-term success and the significance of inducible nonclinical arrhythmias.

BACKGROUND: Radiofrequency (RF) catheter ablation is effective therapy for monomorphic ventricular tachycardia (VT) in patients without structural heart disease. In patients with postinfarction VT; however, this procedure has been used predominantly as adjunctive therapy, targeting only the patient's clinically documented arrhythmia. By targeting all inducible, sustained VT morphologies, we sought to determine the utility of RF catheter ablation as a primary cure in patients who present with hemodynamically tolerated VT. METHODS AND RESULTS: RF ablation was attempted in 35 patients with a previous myocardial infarction and recurrent, hemodynamically tolerated VT. A mean of 3.9+/-2.7 VTs were induced per patient (range, 1 to 10). The clinically documented arrhythmia was successfully ablated in 30 of 35 patients (86%), and on follow-up electrophysiological testing, 11 patients had no inducible VT and were discharged without other therapy. Nineteen patients had inducible "nonclinical" arrhythmias on follow-up testing, and the majority underwent cardiac defibrillator implantation. Freedom from recurrent arrhythmias, including sudden death, was 91% in patients without inducible VT and 53% in patients with persistently inducible "nonclinical" arrhythmias (P<.05; mean follow-up, 17+/-12 and 12+/-11 months, respectively). CONCLUSIONS: In patients with well-tolerated VT, RF catheter ablation may be useful as a primary cure if no other ventricular arrhythmias are inducible on follow-up testing. Ablation of all hemodynamically tolerated arrhythmias should be attempted in patients with multiple inducible VT morphologies because of the high rate of recurrence of unablated VTs in these patients.

The effects of isoproterenol on the cardiac conduction system: site-specific dose dependence.

INTRODUCTION: Isoproterenol is used to assess and facilitate AV nodal conduction, and thus potentiate the induction of supraventricular arrhythmias. It is commonly administered in increasing doses until a predetermined decrease in sinus cycle length, usually 20% to 30%, occurs. This regimen may result in undesirable side effects. We have observed that effects of isoproterenol on the AV node may occur prior to achieving the target sinus cycle length. The purpose of this study was to determine whether the sinus and AV nodes have equal sensitivity to isoproterenol. METHODS AND RESULTS: Thirty-eight consecutive patients, who underwent electrophysiologic evaluation for a variety of indications, were given incremental doses of isoproterenol at 0.007, 0.014, 0.021, and 0.028 microgram/kg per minute. Sinus cycle length and AV node function were assessed at baseline and after 5 minutes at each dose. The percent change from baseline in AV node function was compared with the change in sinus cycle length at each dose interval. Significantly greater decreases were observed in the anterograde and retrograde AV nodal Wenckebach cycle length (P < 0.0001) than in the sinus cycle length at the lowest isoproterenol dose (0.007 microgram/kg per min). These differences were not apparent at higher doses. A sustained supraventricular tachycardia was inducible in 15 of 38 patients in the presence of isoproterenol, of which 40% occurred at the lowest dose. CONCLUSIONS: The AV node is more sensitive than the sinus node to the effects of isoproterenol. Lower doses of isoproterenol than those commonly used may often facilitate the induction of a supraventricular tachyarrhythmia, thus reducing side effects.