Alberto Interian

Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary-artery spasm.

BACKGROUND Silent myocardial ischemia in patients with coronary atherosclerosis is associated with an increased risk of adverse cardiac events, including sudden death. The relation between silent ischemia and the initiation of potentially fatal ventricular arrhythmias has not been defined, however. METHODS As part of a long-term study of sudden cardiac death, data on arrhythmias, coronary anatomy, and responses to ergonovine testing to provoke coronary-artery spasm were collected prospectively among survivors of out-of-hospital cardiac arrest who had no flow-limiting coronary-artery lesions, prior myocardial infarctions, or other structural causes of cardiac arrest and no angina pectoris. Associations between silent myocardial ischemia due to coronary-artery spasm and the occurrence and characteristics of life-threatening ventricular arrhythmias were studied by both invasive and noninvasive techniques. RESULTS Silent ischemic events were associated with the initiation of life-threatening ventricular arrhythmias in five patients with induced or spontaneous focal coronary-artery spasm (or both). These patients were identified among a group of 356 survivors of out-of-hospital cardiac arrest who were evaluated between 1980 and 1991. In two of the five patients reperfusion, rather than ischemia itself, correlated with the onset of the ventricular arrhythmia. Only one of the five had an inducible arrhythmia during electrophysiologic testing. Titration of the dose of a calcium-entry-blocking agent (verapamil, diltiazem, or nifedipine) against the ability of ergonovine to provoke spasm was successful in preventing both the provocation of spasm and arrhythmias in all four patients who were tested. CONCLUSIONS Silent myocardial ischemia due to coronary-artery spasm can initiate potentially fatal arrhythmias in patients without flow-limiting structural coronary-artery lesions. The role of silent ischemia, reperfusion, or both in the initiation of fatal arrhythmias in larger groups of patients with advanced coronary-artery lesions remains to be defined.

Interpretation of Outcomes of Antiarrhythmic Clinical Trials: Design Features and Population Impact

The results of the Cardiac Arrhythmia Suppression Trials (CAST and CAST II) were a watershed in attitudes about management of cardiac arrhythmias.1 2 3 On the basis of the then-prevailing assumption that premature ventricular contractions (PVCs) in the presence of recent myocardial infarction identified a risk for life-threatening arrhythmias and that they also served as the trigger for fatal arrhythmias, it was logical to determine whether suppression of ambient arrhythmias would protect against fatal events.4 Despite the outcomes of these trials, ambient arrhythmias are still viewed as a marker of risk (perhaps somewhat lower than previously thought) and as pathophysiological triggers under proper conditions.5 However, the concept that suppression of asymptomatic PVCs is an appropriate preventive strategy has fallen under the weight of evidence from those studies.6 In addition, new concepts of proarrhythmia emerged from CAST and other sources of information.7 After CAST, a variety of trials testing therapy with other drugs and with implantable devices were implemented, some of which are now completed. The various trials differ in regard to therapeutic strategies, designs, and patient populations. With the flow of new information that has been forthcoming and is anticipated to continue during the next few years, it is important to keep the strengths and limitations of clinical trial designs in perspective and to consider the extent to which the results of any one trial or group of trials can be generalized. This review is intended to analyze general features of trial design that influence their interpretation, application, and clinical impact. It is not intended as a critique of individual trials. The factors discussed include (1) specific outcomes measures; (2) the type of controls used; (3) intention-to-treat versus on-therapy analysis; (4) comparison of therapeutic efficacy, efficiency, and equilibrium; (5) significant negative outcomes; and (6) population …

Time to first shock and clinical outcome in patients receiving an automatic implantable cardioverter-defibrillator

The relation between time to first shock and clinical outcome was studied in 60 patients who received an automatic implantable cardioverter-defibrillator (AICD) from August 1983 through May 1988. The mean (+/- SD) patient age was 64 +/- 10 years, 82% were men and the mean ejection fraction was 33 +/- 13%. During follow-up, 38 patients (63%) had one or more shocks; there were no differences in age, gender distribution or ejection fraction at entry between the shock and no shock groups. Among 51 patients with coronary artery disease, 31 (61%) had one or more shocks, whereas all seven patients with cardiomyopathy had one or more shocks (p less than 0.05). Neither of the two patients with idiopathic ventricular fibrillation had shocks. Of the 13 deaths, 12 occurred during post-hospital follow-up and 1 during the index hospitalization. Of the four sudden post-hospital deaths, only one was due to tachyarrhythmia in the absence of acute myocardial infarction. All four sudden deaths and five of eight post-hospital nonsudden deaths occurred in patients who had had one or more appropriate shocks during follow-up. Eight of the nine first appropriate shocks among patients who subsequently died occurred within the first 3 months of follow-up, but the actual deaths were delayed to a mean of 14.1 +/- 13.9 months (p less than 0.05). The mean time to all deaths was 14.8 +/- 13.1 months. The ejection fraction was significantly lower among patients who died than among patients who survived (25 +/- 7% versus 35 +/- 14%, p less than 0.02), but it did not distinguish risk of first shocks.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical utility of intraatrial pacemaker stored electrograms to diagnose atrial fibrillation and flutter.

POLLAK, W.M., et al.: Clinical Utility of Intraatrial Pacemaker Stored Electrograms to Diagnose Atrial Fibrillation and Flutter. The purpose of this study was to determine if intraatrial electrograms (EGMs) are required to diagnose specific types of atrial tachyarrhythmias detected by pacemaker diagnostics. DDD pacemakers in 56 patients were programmed to store episodes of atrial tachyarrhythmias. Some episodes had a stored atrial EGM snapshot of the atrial tachyarrhythmia. The EGMs were analyzed to confirm whether the stored episodes were true atrial tachyarrhythmias or other pacemaker‐sensed events. EGM confirmation of atrial tachyarrhythmias correlated with increasing duration and rate of episodes. In particular, using EGMs, 8 (18%) of 44 episodes < 10 seconds in duration confirmed atrial tachyarrhythmias compared to 16 (89%) of 18 episodes > 5 minutes in duration (P < 0.001). Only 10 (18%) of 56 detected atrial arrhythmia episodes at rates < 250 complexes per minute were confirmed by the atrial EGM as true arrhythmias compared to 33 (57%) of 58 detected episodes at rates > 250/min (P < 0.001) Twenty‐nine (91%) of 32 EGM confirmed episodes of atrial fibrillation/flutter had an atrial rate > 250 complexes per minute and were a minimum of 10 seconds in duration. Fifteen (88%) of 17 episodes meeting the combined stored data criteria of > 250 complexes per minute and duration > 5 minutes were confirmed as atrial fibrillation or flutter by stored EGMs. Atrial EGMs identified that 71 (62%) of 114 stored high atrial rate (HAR) episodes were events other than true atrial tachyarrhythmias. Pacemaker diagnostic data with intraatrial EGMs can diagnose specific atrial tachyarrhythmias and identify other pacemaker‐sensed events. Stored episodes > 250 complexes per minute and > 5 minutes in duration had a high correlation with atrial fibrillation and flutter.

Reversal of proarrhythmic effects of flecainide acetate and encainide hydrochloride by propranolol.

The use of membrane-active antiarrhythmic agents may be complicated by aggravation of existing arrhythmias or development of new drug-induced arrhythmias. Four patients, referred because of out-of-hospital cardiac arrest or symptomatic sustained ventricular tachycardia, were receiving class IC antiarrhythmic agents in an attempt to prevent inducibility of sustained ventricular tachycardia. New or worsening spontaneous arrhythmias developed while they were on flecainide acetate (n = 3) or encainide hydrochloride (n = 1) therapy. Spontaneous runs of rapid nonsustained and sustained ventricular tachycardia developed in two. Increased frequency of premature ventricular contractions and repetitive forms of ventricular ectopic activity developed in one, despite the fact that inducibility of sustained ventricular tachycardia had been prevented. Salvos and nonsustained ventricular tachycardia developed in the fourth patient. Propranolol had failed to prevent inducibility of sustained ventricular tachycardia during previous programmed stimulation studies in three of the four patients, but it reproducibly suppressed drug-induced arrhythmias that appeared only after administration of the IC agents in each patient. Suppression of the proarrhythmic effects by beta-adrenergic blockade suggests a possible interaction of these drugs with autonomic function in the genesis of the observed proarrhythmic effects. Direct pharmacologic control of proarrhythmic drug effects has not previously been reported.

A shared pathway in atrioventricular nodal reentrant tachycardia and atrial flutter: Implications for pathophysiology and therapy☆

Atrioventricular (AV) nodal reentrant tachycardia and atrial flutter are considered 2 distinct supraventricular tachycardias. Recent clinical and experimental data suggest that both these tachycardias include an area in the lower right atrial septum in their reentrant pathways. This study was designed to test the hypothesis that there is an association between the mechanisms of AV nodal reentrant tachycardia and atrial flutter because of a shared pathway of reentry. Consecutive patients referred for evaluation and management of supraventricular tachycardia, thought to be due to AV nodal reentry, underwent electrophysiologic testing protocols designed to induce both AV nodal reentrant tachycardia and atrial flutter, if present. Fifteen of 29 patients (52%) had both AV nodal reentrant tachycardia and atrial flutter induced during electrophysiologic testing. Seven of these 15 patients (47%) underwent transcatheter radiofrequency current application (mean power 34 +/- 4 W) against the tricuspid annulus above the coronary sinus. In each patient, neither AV nodal reentrant tachycardia nor atrial flutter could be induced after the procedure. Repeat study after successful ablation (mean 6 days) showed no inducible supraventricular arrhythmia of either type at baseline study or during isoproterenol infusion. Atrial flutter occurs frequently (15 of 29 patients; 52%) in patients with AV nodal reentrant tachycardia, because of a shared pathway in their reentry circuits. Because of this shared pathway, both arrhythmias can be ablated at the same site. These observations promote new insights into the mechanism and therapeutics of supraventricular tachycardias.

Efficacy of intravenous propranolol for suppression of inducibility of ventricular tachyarrhythmias with different electrophysiologic characteristics in coronary artery disease

The efficacy of intravenous propranolol for suppression of inducibility of sustained ventricular tachyarrhythmias (VT) was studied in 24 patients who had failed greater than or equal to 1 membrane-active antiarrhythmic drug (mean 2.2 +/- 1.2 drugs/patient). The response to propranolol was compared in 13 patients who had only stable monomorphic VTs inducible at baseline and another 11 patients who had greater than or equal to 1 episode of electrically unstable VTs (polymorphic VT, ventricular flutter or ventricular fibrillation) at baseline. Seven patients (29%) became noninducible (responders) and 17 patients (71%) remained inducible to sustained VT (nonresponders) after propranolol. The basal heart rate was faster in responders than in nonresponders (101 +/- 14 vs 86 +/- 11 beats/min, p less than 0.01). The magnitude of heart rate reduction was also greater after propranolol in responders (from 101 +/- 14 to 80 +/- 9 beats/min, p less than 0.001) than in nonresponders (from 86 +/- 11 to 74 +/- 9 beats/min, p less than 0.01) (p less than 0.05 between the groups), despite equal plasma propranolol concentrations (84 +/- 50 vs 88 +/- 43 ng/ml, difference not significant). Seven of 11 patients (64%) who had greater than or equal to 1 episode of unstable VTs inducible at baseline responded to intravenous propranolol, whereas none of the patients with only stable monomorphic VTs became noninducible after beta blockade (p less than 0.001). Responders had shorter cycle length of inducible VTs than nonresponders (225 +/- 38 vs 302 +/- 66 ms, p less than 0.001). Thus, intravenous propranolol appears to be efficacious in suppressing fast, electrically unstable VTs, compared to monomorphic VTs with slower rates.

Differences in the activation patterns between sustained and self-terminating episodes of human ventricular fibrillation

BACKGROUND. Experimental studies have suggested that R-R interval dynamics during ventricular fibrillation (VF) have organized features, but whether dynamic behavior of non-sustained VF differs from sustained VF is unknown. AIM. The purpose of this study was to investigate whether the dynamics of R-R intervals during non-sustained VF differs from the dynamics during sustained VF. METHODS. A group of 67 patients undergoing routine implantable cardioverter defibrillator (ICD) testing was studied. Forty-three VF events containing mean of 38 local cardiac activation intervals before the termination by ICD shock were analyzed. From intracardiac electrogram recordings, the ratio between the short and long term variability (SD1/SD2) and fractal scaling exponent ( f ) were analyzed. After the initial analyses, data sets were randomized and reanalyzed. Local activation dynamics were then also compared in seven patients with both sustained and spontaneously terminating VF episodes. RESULTS. Randomization caused a change in the VF dynamics from organized toward less organized dynamics ( f ) from 1.08 - 0.57 to 0.81 - 0.45, P < 0.05 and SD1/SD2 from 0.80 - 0.23 to 1.04 - 0.20, P < 0.01). Spontaneously terminating VF showed more organized dynamics than sustained VF terminated by shock (P < 0.05). CONCLUSIONS. Local cardiac activation dynamics during initial phase of human VF shows organized dynamics. Spontaneously terminating VF episodes have more structured dynamics than sustained VF. Thus, the dynamic behavior of local cardiac activation intervals may be related to the maintenance of ventricular tachyarrhythmias.

Pacemaker diagnostics: a critical appraisal of current technology.

POLLAK, W.M., et al .: Pacemaker Diagnostics: A Critical Appraisal of Current Technology. Diagnostic information retrieved from a pacemaker offers the ability to improve patient care. Pacemaker diagnostic data provides information regarding pacemaker function and activity, lead function, arrhythmia occurrence, and data to aid in optimal pacemaker programming. Current pacemakers incorporate greater storage capabilities, more efficient means of storing and presenting data between follow‐up visits, and more options for programming diagnostic functions and algorithms. The cardiac rhythm of the paced patient can be evaluated via real‐time intracardiac electrograms at interrogation, surface electrocardiograms, ambulatory electrocardiograms, and by pacemaker stored diagnostic function that may include stored intracardiac electrograms. This article focuses on the various methods of obtaining diagnostic information regarding pacemaker activity, pacemaker function, and diagnostic information on cardiac arrhythmias. The current clinical applicability and limitations of these methods and the use of stored diagnostic data in the clinical follow‐up and study of patients with pacemakers is discussed. (PACE 2003; 26[Pt. I]:76–98)

The implantable cardioverter-defibrillator: Clinical results

To evaluate the effectiveness of the automatic implantable cardioverter‐defibrillator (AICD), a 7‐year experience, from 1983–1990, was reviewed. A total of 111 patients received an AICD device. Their ages ranged between 8 and 83 years. Mean age was 63.9 years. There were 91 men and 20 women. Eighty of the patients received the AICD following an out‐of‐hospital cardiac arrest, white 32 were suffering from intermittent symptomatic ventricular tachycardia. The underlying etiology in 97 patients (87%) was ischemic coronary artery disease, in 11 patients (10%) dilated cardiomyopathy, and in 3 patients (3%) idiopathic ventricular fibrillation. Mean ejection fraction was 33.2%. Implantation of the AICD was performed via a left thoracotomy in 39 patients, median sternotomy in 49 patients and subxiphoidsubcostal approach in 23 patients. In‐hospital mortality occurred in one patient who suffered an acute myocardial infarction 4 hours postoperatively. Out‐of‐hospital mortality was observed in 19 patients. There were two arrhythmic deaths. Follow‐up was available for 107 patients. Mean follow‐up was 33.1 months. Sixty‐six patients (62%) had AICD shocks. The initial appropriate shocks occurred during the first postimplantation year in 91% of the patients. In 53 of the survivors, initial AICD shocks took place within 4.4 ± 4.7 months from implantation. Thirteen of the 20 patients who died had received appropriate AICD shocks. In these patients, the time between implantation and first shock was 2.7 ± 3.6 months whereas the time between implantation and death was 11.3 ± 10.3 months (NS). We conclude that the AICD is effective in converting ventricular tachyarrhythmias and prolongs survival.