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Biomedical subjects

C D Swerdlow

Publications and source records attributed to C D Swerdlow.

At least 19 recordsLinked to original sources

Long-term outcome in patients who survive out of hospital ventricular fibrillation and undergo electrophysiologic studies: evaluation by electrophysiologic subgroups.

The long-term outcome of 241 survivors of out of hospital ventricular fibrillation who underwent programmed electrical stimulation was evaluated. Patients were categorized according to the rhythm induced at baseline drug-free electrophysiologic testing. Ventricular fibrillation was induced in 39 patients (16%) (Group 1), sustained ventricular tachycardia in 66 patients (27%) (Group 2) and nonsustained ventricular tachycardia in 34 patients (14%) (Group 3); 102 patients (42%) (Group 4) did not have an arrhythmia inducible at baseline electrophysiologic testing. Antiarrhythmic drugs were administered over the long term to 92% of patients in Group 2, 91% of patients in Group 1 and 47% of patients in Group 4. At a mean follow-up time of 30 +/- 15 months, recurrent sudden cardiac death or nonfatal ventricular fibrillation occurred in 11 (28%) of 39 patients with inducible ventricular fibrillation (Group 1), 14 (21%) of 66 patients with inducible sustained ventricular tachycardia (Group 2), 4 (12%) of 34 patients with inducible nonsustained ventricular tachycardia (Group 3) and 16 (16%) of 102 patients without inducible arrhythmias (Group 4). Actuarial analysis revealed a 2 year cumulative arrhythmia-free survival rate of 65% for patients in Group 2, 71% for patients in Group 1, 79% for patients in Group 3 and 81% for patients in Group 4 (p = 0.02). Actuarial survival of patients with inducible sustained ventricular tachycardia or ventricular fibrillation suppressed by electrophysiologically guided drug therapy was not significantly different from that in patients whose arrhythmia was not suppressed. Multivariate regression analysis revealed that only the presence of congestive heart failure was an independent predictor of outcome in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents

Long-term results of antitachycardia pacing in patients with supraventricular tachycardia.

Between 1979 and 1984 the Cybertach-60, (Intermedics, Inc. Model 262-01), a programmable, automatic antitachycardia pacemaker was implanted in 11 patients who had drug-refractory supraventricular tachycardia (SVT). The patients have been followed for a total of 64-108 (mean 84 months). All patients were symptomatic and had failed two or more drugs and six patients had required prior DC cardioversion. The mechanism of supraventricular tachycardia was atrioventricular (AV) nodal reentry in six patients, AV reentry in four patients, and atrial tachycardia in one patient. Preoperatively all patients had reliable termination of the tachycardia without induction of atrial fibrillation by pacing methods available to Cybertach-60. Postimplant, Cybertach-60 reliably terminated all episodes of tachycardia without ancillary drug therapy. Nevertheless, at long-term follow-up antitachycardia pacing was effective and safe in the minority (36%), with only four patients out of eleven still using a pacemaker for supraventricular tachycardia. One of these four patients required additional drug therapy. In one of the patients, the Cybertach-60 was replaced after 78 months by a more advanced device, (Intertach, Intermedics, Inc.) because of a depleted Cybertach-60 battery. In seven patients who no longer use antitachycardia pacing for termination of tachycardia, one patient developed atrial fibrillation during tachycardia termination (at 58 months postimplant). Three patients experienced induction of tachycardia or atrial fibrillation by the pacemaker due to undersensing of sinus P waves (at 36, 48, and 51 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Value of electropharmacologic testing in idiopathic dilated cardiomyopathy and sustained ventricular tachyarrhythmias.

Electrophysiologic studies in 64 patients with idiopathic dilated cardiomyopathy who had sustained ventricular tachycardia or ventricular fibrillation were performed. A sustained ventricular tachyarrhythmia was induced in 43 patients (67%). Electropharmacologic testing predicted an antiarrhythmic drug effective in 15 of 35 patients in whom sustained monomorphic ventricular tachycardia could be induced reproducibly (43% of tested patients, 23% of all patients). During median follow-up of 1.6 years, there were 32 arrhythmia recurrences and 24 cardiac arrests. Multivariate regression analysis identified treatment with a drug predicted to be effective at electropharmacologic testing as the only predictor of freedom from arrhythmia recurrence (p = 0.01); and treatment with a drug predicted to be effective at electropharmacologic testing and lower New York Heart Association functional class as independent predictors of freedom from cardiac arrest (p = 0.03 and p = 0.02, respectively). At median follow-up, the incidences of freedom from arrhythmia recurrence and from cardiac arrest were both 100% during treatment with a drug predicted to be effective at electropharmacologic testing versus 54 +/- 8% and 62 +/- 7%, respectively, during other treatments. These findings indicate that results of electropharmacologic testing accurately predict freedom from arrhythmia recurrence and cardiac arrest in patients with idiopathic dilated cardiomyopathy and sustained ventricular tachyarrhythmias.

Adolescent

Effect of flestolol on ventricular rate during atrial fibrillation in Wolff-Parkinson-White syndrome.

The ultrashort-acting beta blocker flestolol was studied during atrial pacing and atrial fibrillation (AF) in 10 patients with Wolff-Parkinson-White syndrome. Flestolol was given as a 100-micrograms/kg bolus followed by a 10-micrograms/kg/min infusion for 15 minutes. The drug did not alter the antegrade effective refractory period of the accessory pathway or the atrial paced cycle length at which block occurred in the accessory pathway. After flestolol, the percent of preexcited QRS complexes during AF increased (60 +/- 10 vs 87 +/- 5%, p = 0.01). Despite this, the ventricular rate slowed, with increases in mean RR interval (382 +/- 20 vs 416 +/- 22 ms, p = 0.02) and in the shortest interval between preexcited QRS complexes (251 +/- 18 vs 270 +/- 17 ms, p less than 0.01). The effect of isoproterenol 3 to 5 micrograms/min was studied in 5 patients. During atrial pacing, isoproterenol decreased the antegrade refractory period and the atrial paced cycle length of block in the accessory pathway (p less than or equal to 0.05). During AF, it decreased the percent of preexcited QRS complexes, mean RR interval and shortest interval between preexcited QRS complexes (p less than 0.05). Flestolol reversed the effects of isoproterenol both during atrial pacing and AF. Thus, flestolol does not alter conduction over the accessory pathway during atrial pacing, but during AF it slows conduction over the accessory pathway and prevents isoproterenol-mediated increases in ventricular rate. This suggests that in patients with Wolff-Parkinson-White syndrome sympathetic stimulation after the onset of AF enhances conduction over the accessory pathway and is an important determinant of ventricular rate.

Adrenergic beta-Antagonists

Prognostic significance of arrhythmia inducibility or noninducibility at initial electrophysiologic study in survivors of cardiac arrest.

The value of arrhythmia inducibility or noninducibility at initial electrophysiologic study to predict the likelihood of arrhythmia recurrence was assessed in 150 consecutive survivors of cardiac arrest. Ventricular tachycardia (greater than or equal to 6 beats) or ventricular fibrilation was induced in 113 patients (75%); ventricular arrhythmia could not be induced in 37 patients (25%). During follow-up of a mean of 16 months (range 1 to 72), there were 65 arrhythmia recurrences, 34 of them fatal, in 58 patients. Multivariate regression analysis showed that inducibility at initial study of ventricular tachycardia or ventricular fibrilation was an independent predictor of total arrhythmia recurrence (p less than 0.0001) and fatal arrhythmia recurrence (p = 0.02). At 1 year, 25 +/- 5% of patients with an inducible arrhythmia had a fatal arrhythmia recurrence compared with only 4 +/- 4% of patients without (p = 0.003). The nature of the inducible arrhythmia had no additional predictive value. Inducibility or noninducibility of ventricular arrhythmias at initial electrophysiologic study is a powerful, independent predictor of subsequent arrhythmia recurrence in survivors of cardiac arrest. Patients without inducible arrhythmias have a low frequency of fatal arrhythmia recurrence.

Arrhythmias, Cardiac

Strength-interval relation for ventricular functional refractoriness.

Successful initiation and termination of presumed reentrant ventricular tachycardia frequently depends on the ability to deliver closely coupled impulses to the region of the tachycardia origin. To evaluate systematically the relative influence of local latency and large-scale conduction delay in limiting the delivery of closely coupled impulses, the strength-interval relation of the effective refractory period (RP), and the local and remote functional RP in 35 patients at paced cycle length of 500 ms were measured. The pacing threshold was less than or equal to 0.25 mA in all patients. The drive-train (S1) and the extrastimulus (S2) were applied from the same site, the right ventricular (RV) apex, in 25 patients, and from separate sites (RV apex and RV outflow tract) in 10 patients. The effect of procainamide (plasma concentration 10.1 +/- 2.3 micrograms/ml) on the strength-interval relations in 10 patients was also assessed. Although effective RP decreased significantly with each successive increase in current strength (p less than 0.001), local functional RP decreased only up to current strength of 4 mA, and remote functional RP decreased only up to 2 mA. Procainamide shifted the effective RP and local and remote functional RP strength-interval curves uniformly to the right without altering their relation. These data indicate that large-scale conduction delay provides the principal limitation for using increasing current strengths of a single extrastimulus to initiate or terminate ventricular tachycardia.

Adult

Pharmacodynamics of procainamide in patients with ventricular tachyarrhythmias.

The onset and offset of the electropharmacologic effect of procainamide was studied in nine patients with ventricular arrhythmias. Procainamide was given at a constant infusion rate of 0.27 +/- 0.05 mg/kg/min for 50 to 60 minutes to an average total dose of 15.5 +/- 4.4 mg/kg. The QRS interval (used as an index of electropharmacologic effect) at a paced cycle length of 500 ms, and the plasma procainamide concentration were measured simultaneously every 5 minutes during infusion and at frequent intervals for up to 4 hours during a washout period. The average peak plasma concentration was 15.8 +/- 9.6 micrograms/ml and the average maximum QRS interval prolongation was 23.9 +/- 6.8% from baseline. The temporal and static plasma concentration-effect relationships were evaluated by pharmacodynamic modeling and linear regression. For six patients, there was a minimal (less than 2 minutes) delay in the plasma concentration-effect relationship, and the data fit a linear relationship with an average slope of 3.2 +/- 1.1 msec/microgram/ml. For the other three patients, there was a significant delay (3, 10, and 18 minutes respectively) in the plasma concentration-effect relationship. In most patients, the electropharmacologic effect of procainamide is rapid and proportional to plasma concentration; but in a minority of patients, significant delay occurs and could influence the results and interpretation of electropharmacologic studies.

Adult

Long-segment coronary ulcerations in survivors of sudden cardiac death.

Angiographically irregular coronary stenoses usually represent plaque rupture with or without superimposed thrombi. Long-segment coronary stenoses with diffuse irregularities (type IIB morphology) have been shown to be more prevalent than focal irregular lesions (type IIA morphology) in survivors of cardiac arrest without acute myocardial infarction. To further understand the pathogenetic importance of type IIB morphology, the clinical and angiographic characteristics in 59 such patients were analyzed. Type IIB lesions accounted for 63% of all type II lesions. Type IIB patients were older than type IIA patients (p less than 0.05). There was a tendency for type IIB morphology to be associated with more extensive disease than other types of lesion morphology (p less than 0.10). Type IIB morphology probably reflects more advanced atherosclerosis. Platelet microemboli may precipitate spasm and/or acute ischemic ventricular tachyarrhythmias. It is possible that long-segment coronary ulcerations are associated with a higher risk for local coronary thromboembolism, and hence with sudden death, than focal lesions.

Aged

Angiographic coronary morphology in survivors of cardiac arrest.

Autopsy studies in victims of sudden coronary death revealed intramyocardial platelet aggregates with microscopic myonecrosis downstream from ruptured atherosclerotic plaques. Ruptured plaques usually manifest angiographically as irregularly bordered (type II) lesions. To investigate the possible pathogenic role of ruptured plaques in arrhythmic death, we analyzed clinical, angiographic, and electrophysiologic data from 49 survivors of cardiac arrest without acute myocardial infarction. All patients had greater than or equal to 50% stenoses of greater than or equal to one coronary artery; 16 had type II morphology, and 33 did not. Type II morphology was more prevalent in patients without inducible sustained monomorphic ventricular tachycardia (11 of 22 or 50%) than in those with it (five of 27 or 19%), p less than 0.05, and patients without akinetic or dyskinetic segments (eight of 14 or 57%) than in those with them (eight of 34 or 24%), p less than 0.06. Thus type II morphology is more prevalent in patients without a demonstrable anatomic and/or electrophysiologic substrate for reentrant ventricular tachycardia, indirectly implicating ruptured plaques in the pathogenesis of cardiac arrest in this subset of patients.

Aged

Tocainide for drug-resistant sustained ventricular tachyarrhythmias.

Eighty-two patients with drug-resistant ventricular tachycardia or fibrillation were treated with oral tocainide. Treatment in 54 patients, all with inducible ventricular tachycardia or fibrillation at baseline electrophysiologic testing, was based on the results of invasive electrophysiologic testing. Twenty-eight additional patients with frequent spontaneous ventricular tachycardia or no inducible arrhythmia during electrophysiologic testing were treated on the basis of the findings of electrocardiographic (ECG) Holter monitoring. Tocainide was effective in 7 (13%) and partially effective in 5 (8%) of the 54 patients in the electrophysiologic study group and was effective in 17 (61%) of the 28 patients in the ECG monitoring group. History of previous myocardial infarction and failure of response to lidocaine correlated with failure to respond to tocainide. Side effects were common both during initial therapy and during long-term treatment and necessitated discontinuation of tocainide therapy in 17% of the patients. At a mean follow-up period of 14 months, 13 patients are still receiving tocainide and are arrhythmia-free. In conclusion, the usefulness of oral tocainide in the management of drug-refractory sustained ventricular tachycardia or fibrillation is limited because of its low effectiveness and frequent side effects.

Anti-Arrhythmia Agents

Clinical predictors of arrhythmia inducibility in survivors of cardiac arrest: importance of gender and prior myocardial infarction.

Clinical characteristics that correlate with arrhythmia inducibility were determined in 150 consecutive survivors of cardiac arrest. All underwent electrophysiologic study with a uniform protocol when they were not receiving antiarrhythmic drugs. A ventricular tachyarrhythmia (sustained monomorphic ventricular tachycardia, ventricular fibrillation or nonsustained ventricular tachycardia) was induced in 113 patients (75%). The strongest correlates of inducing a tachyarrhythmia were male gender (p less than 0.0001) and a history of prior myocardial infarction (p less than 0.0001). Induction of sustained monomorphic tachycardia alone was also strongly related to gender and prior infarction; in particular, none of 26 women without prior infarction had induction of sustained monomorphic ventricular tachycardia. Among patients with induced sustained tachyarrhythmias, those with induced monomorphic ventricular tachycardia were distinguished from those with induced ventricular fibrillation in they were more likely to have coronary artery disease (p = 0.0001), healed myocardial infarction (p = 0.0002), left ventricular aneurysm (p = 0.0007) and ventricular tachycardia documented at the time of cardiac arrest (p = 0.02). Other variables showing significant correlations with arrhythmia inducibility were ejection fraction, documentation of ventricular tachycardia at the time of cardiac arrest and presence of an intraventricular conduction delay. However, stepwise logistic regression identified male gender and healed myocardial infarction as the only independent predictors of arrhythmia inducibility. On the basis of these two variables alone, arrhythmia inducibility or noninducibility could be correctly predicted in 89% of the patients in this series.

Arrhythmias, Cardiac

Cycle length dependence of human action potential duration in vivo. Effects of single extrastimuli, sudden sustained rate acceleration and deceleration, and different steady-state frequencies.

Using a new method for long-term recording of monophasic action potentials from the human heart, we studied in 17 patients the effects on ventricular action potential duration (APD) of three clinically pertinent cycle length perturbations: (1) single extrastimuli, (2) abrupt sustained rate acceleration and deceleration, and (3) different steady-state cycle lengths. Results were: (a) APD after single extrastimuli at progressively longer cycle lengths were related to the extrastimulus cycle length with a biphasic electrical restitution curve which after an initial steep rise and a subsequent transient descent rose again more gradually to a plateau at cycle lengths above 800-1,000 ms. (b) After a sustained step decrease in cycle length, the first APD shortened abruptly while final steady-state adaptation required up to several minutes. The transition between the rapid and slow phase of APD change was characterized by a variable alternans of APD which correlated inversely with the preceding diastolic interval. (c) In the steady state, APD correlated linearly with cycle length, increasing an average of 23 ms per 100 ms cycle length increase (r = 0.995). The divergence between steady-state and non-steady-state APD, and the slowness of steady-state adaptation, are important factors to be considered in clinical electrophysiologic studies and in rate correction algorithms of APD or QT intervals, respectively.

Action Potentials

Electrophysiology and antiarrhythmic efficacy of intravenous pirmenol in patients with sustained ventricular tachyarrhythmias.

We assessed the electrophysiologic effects and antiarrhythmic efficacy of intravenous pirmenol in 15 patients who had spontaneous and induced sustained ventricular tachyarrhythmias. At a plasma concentration of 2.29 +/- 0.75 micrograms/ml, pirmenol decreased sinus cycle length by 11 +/- 13%, increased QRS, QTc, and HV intervals by 14 +/- 12%, 13 +/- 12%, and 22 +/- 28%, respectively, and increased atrial and ventricular effective refractory periods (ERP) by 20 +/- 14% and 7 +/- 8%, respectively. There was a greater increase in QRS duration during ventricular tachycardia and ventricular pacing than during sinus rhythm (p less than 0.005). By electropharmacologic testing, pirmenol was judged effective in six patients (40%) and was proarrhythmic in one (6%). In the nine patients in whom pirmenol was judged ineffective, the cycle length of induced VT increased by 36 +/- 15% and the associated mean arterial pressure increased by 21 +/- 14 mm Hg. The only side effects were mild hypotension and mild nausea in one patient each. Intravenous pirmenol has type IA electrophysiologic effects. It can be administered safely to patients with sustained ventricular tachyarrhythmias and is as effective as approved antiarrhythmic drugs when assessed by electropharmacologic testing.

Adult

Long-term follow-up after surgical correction of Wolff-Parkinson-White syndrome.

The long-term efficacy of surgical correction of Wolff-Parkinson-White syndrome was evaluated in 45 consecutive patients. Before surgery, 42 patients had reciprocating tachycardia and 12 had atrial fibrillation. The principal operative procedure was endocardial incision in 42 patients, endocardial cryoablation in 2 patients and epicardial cryoablation without dissection of the atrioventricular (AV) fat pad in 1 patient. Two patients had perioperative complications. One patient had bleeding that necessitated reoperation, and one had a right cerebral stroke with subsequent clearing of neurologic deficit. At postoperative electrophysiologic study, only the patient who underwent epicardial cryoablation had conduction over an accessory connection. Two others had intermittent delta waves in the early postoperative period but no accessory connection conduction at electrophysiologic study. During a mean follow-up of 3.1 years, the patient with ineffective cryoablation had recurrent orthodromic tachycardia, and one other patient had late recurrence of delta waves without arrhythmias. Four other patients had frequent palpitation, which was caused by premature ventricular complexes in three and sinus tachycardia in one. Seventeen patients had occasional "skipped beats" without recurrence of tachyarrhythmias. Twelve of 13 patients whose arrhythmias limited employment before surgery returned to work after surgery. By actuarial analysis at 1, 2 and 3 years, all patients were alive and 98% were free from tachyarrhythmias. Surgical correction of Wolff-Parkinson-White syndrome provides excellent long-term results with low morbidity. Patients who are disabled by arrhythmias return to work after successful surgery. Delta waves may persist or recur without return of arrhythmias. Minor postoperative episodes of palpitation are common and do not correlate with tachyarrhythmias.

Endocardium

Differential electrophysiologic properties of decremental retrograde pathways in long RP' tachycardia.

Long RP' supraventricular tachycardias (SVT) often demonstrate both slow and decremental conduction properties in the retrograde pathway of the reentrant circuit. The electrophysiologic properties of these pathways are poorly understood. We studied 10 patients with long RP' SVT (RP'/RR, 0.52 to 0.71); five had the unusual form of atrioventricular nodal reentry (fast-slow) and five patients had accessory AV pathways with slow, decremental retrograde conduction properties. During SVT, the effects of intravenous adenosine (37.5 to 150 micrograms/kg), which increases potassium current (iK) in supraventricular tissue and hyperpolarizes membrane potential toward Ek (-90 mV), and the response to slow-inward channel blockade with verapamil (0.10 to 0.20 mg/kg iv) were evaluated. Adenosine and verapamil has similar effects in the presence of fast-slow AV nodal reentry since both agents terminated SVT by producing block in the retrograde slow AV nodal pathway. In contrast, adenosine and verapamil had differential effects on retrograde conduction in decremental accessory pathways. Adenosine terminated all episodes of SVT in the retrograde decremental pathway, whereas verapamil had a direct effect on this tissue in only two of five patients. Decremental retrograde accessory pathways can therefore demonstrate at least two types of electrophysiologic responses. Pathways that respond only to adenosine-induced hyperpolarizing K+ current likely comprise depressed fast-Na+ channel tissue, i.e., partially depolarized (greater than -60 to -70 mV) atrial tissue. In contrast, decremental accessory pathways that respond to both modulation of the slow-inward calcium current and K+ conductance have pharmacologic properties similar to those of the AV node and may represent more completely depolarized atrial fibers with resting membrane potentials of -60 mV or less.

Adenosine